labmate-mcp 7.0.0__py3-none-any.whl

labmate_mcp/bench.py

@@ -0,0 +1,3392 @@
+"""
+bench.py — Bench chemistry calculators and reference databases.
+
+Pure-computation tools for lab work: molarity, dilution, yield, and mass calculations,
+plus comprehensive reference data for named reactions, protecting groups, workup
+procedures, solvents, cooling baths, TLC stains, and column chromatography.
+
+No API keys required. Works out of the box.
+"""
+
+from __future__ import annotations
+
+import math
+import re
+from typing import Optional
+
+# =============================================================================
+# Constants — Molecular weight helpers
+# =============================================================================
+
+ATOMIC_WEIGHTS = {
+    "H": 1.008, "He": 4.003, "Li": 6.941, "Be": 9.012, "B": 10.81,
+    "C": 12.011, "N": 14.007, "O": 15.999, "F": 18.998, "Ne": 20.180,
+    "Na": 22.990, "Mg": 24.305, "Al": 26.982, "Si": 28.086, "P": 30.974,
+    "S": 32.065, "Cl": 35.453, "Ar": 39.948, "K": 39.098, "Ca": 40.078,
+    "Sc": 44.956, "Ti": 47.867, "V": 50.942, "Cr": 51.996, "Mn": 54.938,
+    "Fe": 55.845, "Co": 58.933, "Ni": 58.693, "Cu": 63.546, "Zn": 65.38,
+    "Ga": 69.723, "Ge": 72.64, "As": 74.922, "Se": 78.96, "Br": 79.904,
+    "Kr": 83.798, "Rb": 85.468, "Sr": 87.62, "Y": 88.906, "Zr": 91.224,
+    "Nb": 92.906, "Mo": 95.96, "Ru": 101.07, "Rh": 102.906, "Pd": 106.42,
+    "Ag": 107.868, "Cd": 112.411, "In": 114.818, "Sn": 118.710, "Sb": 121.760,
+    "Te": 127.60, "I": 126.904, "Xe": 131.293, "Cs": 132.905, "Ba": 137.327,
+    "La": 138.905, "Ce": 140.116, "Pr": 140.908, "Nd": 144.242, "Sm": 150.36,
+    "Eu": 151.964, "Gd": 157.25, "Tb": 158.925, "Dy": 162.500, "Ho": 164.930,
+    "Er": 167.259, "Tm": 168.934, "Yb": 173.054, "Lu": 174.967, "Hf": 178.49,
+    "Ta": 180.948, "W": 183.84, "Re": 186.207, "Os": 190.23, "Ir": 192.217,
+    "Pt": 195.084, "Au": 196.967, "Hg": 200.59, "Tl": 204.383, "Pb": 207.2,
+    "Bi": 208.980, "Th": 232.038, "U": 238.029,
+}
+
+
+def parse_formula(formula: str) -> float:
+    """Parse a molecular formula string and return molecular weight.
+    Handles nested parentheses, e.g. Ca(OH)2, Mg3(PO4)2."""
+    formula = formula.strip()
+    # Recursive approach: handle parentheses first
+    while "(" in formula:
+        # Find innermost parentheses
+        m = re.search(r"\(([^()]+)\)(\d*)", formula)
+        if not m:
+            break
+        inner = m.group(1)
+        mult = int(m.group(2)) if m.group(2) else 1
+        # Expand: multiply each element count
+        inner_mw = _sum_elements(inner)
+        # Replace with placeholder
+        formula = formula[:m.start()] + f"[{inner_mw * mult}]" + formula[m.end():]
+
+    # Now parse remaining, including placeholders
+    total = 0.0
+    # Handle bracketed MW values from parenthesis expansion
+    for bm in re.finditer(r"\[([\d.]+)\]", formula):
+        total += float(bm.group(1))
+    formula_clean = re.sub(r"\[[\d.]+\]", "", formula)
+    total += _sum_elements(formula_clean)
+    return total
+
+
+def _sum_elements(s: str) -> float:
+    """Sum molecular weights of elements in a simple formula (no parentheses)."""
+    total = 0.0
+    for m in re.finditer(r"([A-Z][a-z]?)(\d*)", s):
+        elem = m.group(1)
+        count = int(m.group(2)) if m.group(2) else 1
+        if elem in ATOMIC_WEIGHTS:
+            total += ATOMIC_WEIGHTS[elem] * count
+    return total
+
+
+# =============================================================================
+# Calculator: Molarity & Solutions
+# =============================================================================
+
+def calc_molarity(
+    *,
+    concentration: float | None = None,
+    mass_grams: float | None = None,
+    moles: float | None = None,
+    volume_ml: float | None = None,
+    volume_l: float | None = None,
+    mw: float | None = None,
+    formula: str | None = None,
+) -> dict:
+    """Multi-purpose molarity/solution calculator.
+
+    Provide 2-3 of: concentration (M), mass (g), moles, volume (mL or L), MW.
+    Solves for unknowns using M = n/V, n = mass/MW.
+    """
+    # Resolve volume to liters
+    vol_l = None
+    if volume_l is not None:
+        vol_l = volume_l
+    elif volume_ml is not None:
+        vol_l = volume_ml / 1000.0
+
+    # Resolve MW from formula if needed
+    if mw is None and formula:
+        mw = parse_formula(formula)
+
+    # Resolve moles from mass and MW
+    if moles is None and mass_grams is not None and mw is not None and mw > 0:
+        moles = mass_grams / mw
+
+    # Resolve mass from moles and MW
+    if mass_grams is None and moles is not None and mw is not None:
+        mass_grams = moles * mw
+
+    # M = n / V
+    if concentration is None and moles is not None and vol_l is not None and vol_l > 0:
+        concentration = moles / vol_l
+    if moles is None and concentration is not None and vol_l is not None:
+        moles = concentration * vol_l
+    if vol_l is None and concentration is not None and moles is not None and concentration > 0:
+        vol_l = moles / concentration
+
+    # Re-derive mass if we now have moles
+    if mass_grams is None and moles is not None and mw is not None:
+        mass_grams = moles * mw
+    if moles is None and mass_grams is not None and mw is not None and mw > 0:
+        moles = mass_grams / mw
+
+    return {
+        "molarity_M": _r(concentration),
+        "moles_mol": _r(moles),
+        "mass_g": _r(mass_grams),
+        "volume_mL": _r(vol_l * 1000) if vol_l is not None else None,
+        "volume_L": _r(vol_l),
+        "mw_g_per_mol": _r(mw),
+    }
+
+
+def _r(v, dp=6):
+    if v is None:
+        return None
+    return round(v, dp)
+
+
+# =============================================================================
+# Calculator: Dilution (C₁V₁ = C₂V₂)
+# =============================================================================
+
+def calc_dilution(
+    *,
+    c1: float | None = None,
+    v1: float | None = None,
+    c2: float | None = None,
+    v2: float | None = None,
+    c1_unit: str = "M",
+    v1_unit: str = "mL",
+    c2_unit: str = "M",
+    v2_unit: str = "mL",
+) -> dict:
+    """C₁V₁ = C₂V₂ dilution calculator. Solves for the one missing value."""
+    # Normalize concentrations to M
+    c1_m = _to_molar(c1, c1_unit) if c1 is not None else None
+    c2_m = _to_molar(c2, c2_unit) if c2 is not None else None
+    v1_ml = _to_ml(v1, v1_unit) if v1 is not None else None
+    v2_ml = _to_ml(v2, v2_unit) if v2 is not None else None
+
+    nones = sum(1 for x in [c1_m, v1_ml, c2_m, v2_ml] if x is None)
+    if nones != 1:
+        return {"error": f"Provide exactly 3 of 4 values (c1, v1, c2, v2). Got {4 - nones} values."}
+
+    if c1_m is None:
+        c1_m = (c2_m * v2_ml) / v1_ml
+    elif v1_ml is None:
+        v1_ml = (c2_m * v2_ml) / c1_m
+    elif c2_m is None:
+        c2_m = (c1_m * v1_ml) / v2_ml
+    elif v2_ml is None:
+        v2_ml = (c1_m * v1_ml) / c2_m
+
+    solvent_to_add = v2_ml - v1_ml if v1_ml is not None and v2_ml is not None else None
+
+    return {
+        "c1": _r(c1_m), "c1_unit": "M",
+        "v1_mL": _r(v1_ml),
+        "c2": _r(c2_m), "c2_unit": "M",
+        "v2_mL": _r(v2_ml),
+        "solvent_to_add_mL": _r(solvent_to_add) if solvent_to_add and solvent_to_add > 0 else None,
+        "dilution_factor": _r(c1_m / c2_m) if c1_m and c2_m else None,
+    }
+
+
+def _to_molar(val: float, unit: str) -> float:
+    u = unit.lower().strip()
+    if u in ("m", "mol/l"):
+        return val
+    if u in ("mm", "mmol/l"):
+        return val / 1000.0
+    if u in ("um", "µm", "μm", "umol/l"):
+        return val / 1_000_000.0
+    if u in ("nm", "nmol/l"):
+        return val / 1_000_000_000.0
+    if u in ("mg/ml", "g/l"):
+        return val  # user needs MW to convert; treat as direct
+    return val  # assume M
+
+
+def _to_ml(val: float, unit: str) -> float:
+    u = unit.lower().strip()
+    if u in ("ml",):
+        return val
+    if u in ("l",):
+        return val * 1000.0
+    if u in ("ul", "µl", "μl"):
+        return val / 1000.0
+    return val  # assume mL
+
+
+# =============================================================================
+# Calculator: Reaction Mass / Equivalents
+# =============================================================================
+
+def calc_reaction_mass(
+    reagents: list[dict],
+) -> dict:
+    """Calculate masses/volumes needed for a reaction.
+
+    Each reagent dict should have:
+      - name: str
+      - mw: float (g/mol) OR formula: str
+      - equiv: float (equivalents, default 1.0)
+      - AND one of: mass_g, moles, volume_ml + density
+    Optional per reagent:
+      - density: float (g/mL) for liquid reagents
+      - molarity: float (M) for solutions
+      - volume_ml: float
+
+    The first reagent with mass_g or moles is the reference.
+    """
+    results = []
+    ref_moles = None
+
+    # First pass: resolve MW and find reference moles
+    for r in reagents:
+        mw = r.get("mw")
+        if mw is None and r.get("formula"):
+            mw = parse_formula(r["formula"])
+        r["_mw"] = mw
+
+        equiv = r.get("equiv", 1.0)
+        r["_equiv"] = equiv
+
+        # Find reference compound (first with defined moles)
+        if ref_moles is None:
+            if r.get("moles"):
+                ref_moles = r["moles"] / equiv
+            elif r.get("mass_g") and mw and mw > 0:
+                ref_moles = (r["mass_g"] / mw) / equiv
+            elif r.get("volume_ml") and r.get("density") and mw and mw > 0:
+                mass = r["volume_ml"] * r["density"]
+                ref_moles = (mass / mw) / equiv
+            elif r.get("volume_ml") and r.get("molarity"):
+                mol = r["volume_ml"] / 1000.0 * r["molarity"]
+                ref_moles = mol / equiv
+
+    if ref_moles is None:
+        return {"error": "Could not determine reference moles. Provide mass_g or moles for at least one reagent."}
+
+    # Second pass: compute all quantities
+    for r in reagents:
+        mw = r["_mw"]
+        equiv = r["_equiv"]
+        moles_needed = ref_moles * equiv
+
+        entry = {
+            "name": r.get("name", "?"),
+            "mw": _r(mw),
+            "equiv": equiv,
+            "moles": _r(moles_needed, 6),
+            "mmoles": _r(moles_needed * 1000, 4),
+        }
+
+        if mw and mw > 0:
+            entry["mass_g"] = _r(moles_needed * mw, 4)
+            entry["mass_mg"] = _r(moles_needed * mw * 1000, 2)
+
+        density = r.get("density")
+        if density and mw and mw > 0:
+            vol = (moles_needed * mw) / density
+            entry["volume_mL"] = _r(vol, 4)
+            entry["volume_uL"] = _r(vol * 1000, 1)
+
+        molarity = r.get("molarity")
+        if molarity and molarity > 0:
+            vol_l = moles_needed / molarity
+            entry["volume_mL"] = _r(vol_l * 1000, 4)
+            entry["volume_uL"] = _r(vol_l * 1_000_000, 1)
+
+        results.append(entry)
+
+    return {
+        "ref_moles_1_equiv": _r(ref_moles, 6),
+        "reagents": results,
+    }
+
+
+# =============================================================================
+# Calculator: Yield
+# =============================================================================
+
+def calc_yield(
+    *,
+    actual_mass_g: float | None = None,
+    theoretical_mass_g: float | None = None,
+    limiting_moles: float | None = None,
+    limiting_mass_g: float | None = None,
+    limiting_mw: float | None = None,
+    limiting_formula: str | None = None,
+    product_mw: float | None = None,
+    product_formula: str | None = None,
+    stoich_coeff_product: float = 1.0,
+    stoich_coeff_limiting: float = 1.0,
+    percent_yield: float | None = None,
+) -> dict:
+    """Calculate theoretical yield and percent yield."""
+    # Resolve MWs
+    if limiting_mw is None and limiting_formula:
+        limiting_mw = parse_formula(limiting_formula)
+    if product_mw is None and product_formula:
+        product_mw = parse_formula(product_formula)
+
+    # Resolve moles of limiting reagent
+    if limiting_moles is None and limiting_mass_g is not None and limiting_mw:
+        limiting_moles = limiting_mass_g / limiting_mw
+
+    # Theoretical moles of product
+    theo_moles = None
+    if limiting_moles is not None:
+        theo_moles = limiting_moles * (stoich_coeff_product / stoich_coeff_limiting)
+
+    # Theoretical mass
+    if theoretical_mass_g is None and theo_moles is not None and product_mw:
+        theoretical_mass_g = theo_moles * product_mw
+
+    # Percent yield
+    if percent_yield is None and actual_mass_g is not None and theoretical_mass_g:
+        percent_yield = (actual_mass_g / theoretical_mass_g) * 100.0
+
+    # Recover actual mass from percent yield
+    if actual_mass_g is None and percent_yield is not None and theoretical_mass_g:
+        actual_mass_g = (percent_yield / 100.0) * theoretical_mass_g
+
+    # Atom economy (if we have both MWs)
+    atom_economy = None
+    if product_mw and limiting_mw:
+        atom_economy = (product_mw * stoich_coeff_product) / (limiting_mw * stoich_coeff_limiting) * 100.0
+        if atom_economy > 100:
+            atom_economy = None  # doesn't make sense w/o all reactants
+
+    return {
+        "limiting_moles": _r(limiting_moles),
+        "theoretical_moles_product": _r(theo_moles),
+        "theoretical_mass_g": _r(theoretical_mass_g, 4),
+        "actual_mass_g": _r(actual_mass_g, 4),
+        "percent_yield": _r(percent_yield, 2),
+        "product_mw": _r(product_mw),
+        "limiting_mw": _r(limiting_mw),
+    }
+
+
+# =============================================================================
+# Calculator: Concentration Interconversion
+# =============================================================================
+
+def calc_concentration(
+    *,
+    value: float,
+    from_unit: str,
+    to_unit: str,
+    mw: float | None = None,
+    formula: str | None = None,
+    density_solution: float = 1.0,  # g/mL
+) -> dict:
+    """Convert between concentration units.
+
+    Supported units: M, mM, uM, nM, mg/mL, g/L, ug/mL, %w/v, %w/w, %v/v, ppm, ppb, mol/L, mmol/L.
+    MW is required for conversions between molar and mass-based units.
+    """
+    if mw is None and formula:
+        mw = parse_formula(formula)
+
+    # Normalize everything to mol/L (M) if molar, or mg/mL if mass-based
+    # We convert to an intermediate: mg/mL AND mol/L where possible
+
+    u_from = from_unit.lower().strip().replace(" ", "")
+    u_to = to_unit.lower().strip().replace(" ", "")
+
+    # Convert from_unit → mg/mL
+    mg_per_ml = None
+    mol_per_l = None
+
+    if u_from in ("m", "mol/l"):
+        mol_per_l = value
+        if mw:
+            mg_per_ml = value * mw  # M * g/mol = g/L = mg/mL
+    elif u_from in ("mm", "mmol/l"):
+        mol_per_l = value / 1000.0
+        if mw:
+            mg_per_ml = mol_per_l * mw
+    elif u_from in ("um", "µm", "μm", "umol/l"):
+        mol_per_l = value / 1e6
+        if mw:
+            mg_per_ml = mol_per_l * mw
+    elif u_from in ("nm", "nmol/l"):
+        mol_per_l = value / 1e9
+        if mw:
+            mg_per_ml = mol_per_l * mw
+    elif u_from in ("mg/ml", "g/l"):
+        mg_per_ml = value
+        if mw and mw > 0:
+            mol_per_l = value / mw
+    elif u_from in ("ug/ml", "µg/ml", "mg/l"):
+        mg_per_ml = value / 1000.0
+        if mw and mw > 0:
+            mol_per_l = mg_per_ml / mw
+    elif u_from in ("ng/ml", "ug/l", "µg/l"):
+        mg_per_ml = value / 1e6
+        if mw and mw > 0:
+            mol_per_l = mg_per_ml / mw
+    elif u_from in ("%w/v", "%(w/v)"):
+        mg_per_ml = value * 10.0  # 1% w/v = 1 g/100 mL = 10 mg/mL
+        if mw and mw > 0:
+            mol_per_l = (mg_per_ml) / mw
+    elif u_from in ("%w/w", "%(w/w)"):
+        mg_per_ml = value * 10.0 * density_solution
+        if mw and mw > 0:
+            mol_per_l = mg_per_ml / mw
+    elif u_from in ("ppm",):
+        mg_per_ml = value / 1000.0  # 1 ppm = 1 mg/L = 0.001 mg/mL
+        if mw and mw > 0:
+            mol_per_l = mg_per_ml / mw
+    elif u_from in ("ppb",):
+        mg_per_ml = value / 1e6
+        if mw and mw > 0:
+            mol_per_l = mg_per_ml / mw
+    else:
+        return {"error": f"Unknown source unit: {from_unit}"}
+
+    # Convert mg/mL or mol/L → target unit
+    result = None
+
+    if u_to in ("m", "mol/l"):
+        result = mol_per_l
+    elif u_to in ("mm", "mmol/l"):
+        result = mol_per_l * 1e3 if mol_per_l is not None else None
+    elif u_to in ("um", "µm", "μm", "umol/l"):
+        result = mol_per_l * 1e6 if mol_per_l is not None else None
+    elif u_to in ("nm", "nmol/l"):
+        result = mol_per_l * 1e9 if mol_per_l is not None else None
+    elif u_to in ("mg/ml", "g/l"):
+        result = mg_per_ml
+    elif u_to in ("ug/ml", "µg/ml", "mg/l"):
+        result = mg_per_ml * 1e3 if mg_per_ml is not None else None
+    elif u_to in ("ng/ml", "ug/l", "µg/l"):
+        result = mg_per_ml * 1e6 if mg_per_ml is not None else None
+    elif u_to in ("%w/v", "%(w/v)"):
+        result = mg_per_ml / 10.0 if mg_per_ml is not None else None
+    elif u_to in ("%w/w", "%(w/w)"):
+        result = (mg_per_ml / (10.0 * density_solution)) if mg_per_ml is not None else None
+    elif u_to in ("ppm",):
+        result = mg_per_ml * 1000.0 if mg_per_ml is not None else None
+    elif u_to in ("ppb",):
+        result = mg_per_ml * 1e6 if mg_per_ml is not None else None
+    else:
+        return {"error": f"Unknown target unit: {to_unit}"}
+
+    if result is None:
+        return {"error": f"Cannot convert from {from_unit} to {to_unit} without molecular weight."}
+
+    return {
+        "input_value": value,
+        "input_unit": from_unit,
+        "result_value": _r(result, 6),
+        "result_unit": to_unit,
+        "mw_used": _r(mw) if mw else None,
+        "density_used": density_solution if u_from in ("%w/w", "%(w/w)") or u_to in ("%w/w", "%(w/w)") else None,
+        "intermediate_mg_per_mL": _r(mg_per_ml, 6) if mg_per_ml is not None else None,
+        "intermediate_mol_per_L": _r(mol_per_l, 9) if mol_per_l is not None else None,
+    }
+
+
+# =============================================================================
+# Named Reactions Database
+# =============================================================================
+
+NAMED_REACTIONS: dict[str, dict] = {}
+
+def _nr(name, *, aliases=None, category="", type_="", summary="",
+        conditions="", substrate="", limitations="", mechanism="",
+        refs="", related="", functional_groups=""):
+    """Register a named reaction."""
+    key = name.lower()
+    NAMED_REACTIONS[key] = {
+        "name": name,
+        "aliases": aliases or [],
+        "category": category,
+        "type": type_,
+        "summary": summary,
+        "conditions": conditions,
+        "substrate": substrate,
+        "limitations": limitations,
+        "mechanism": mechanism,
+        "refs": refs,
+        "related": related,
+        "functional_groups": functional_groups,
+    }
+    # Also register aliases
+    for a in (aliases or []):
+        NAMED_REACTIONS[a.lower()] = NAMED_REACTIONS[key]
+
+
+# --- C-C Bond Formation: Cross-Coupling ---
+
+_nr("Suzuki Coupling",
+    aliases=["Suzuki-Miyaura", "Suzuki reaction"],
+    category="C-C Bond Formation", type_="Cross-Coupling",
+    summary="Pd-catalyzed coupling of organoboron compounds (boronic acids/esters) with organic halides or triflates.",
+    conditions="Pd(PPh3)4 or Pd(dppf)Cl2 (0.5-5 mol%), base (K2CO3, Cs2CO3, K3PO4), solvent (THF, dioxane, DMF/H2O), 60-100°C. Aqueous conditions possible.",
+    substrate="Aryl/vinyl boronic acids + aryl/vinyl halides (I > Br >> Cl) or triflates. sp2-sp2 coupling preferred. sp2-sp3 possible with specialized ligands (SPhos, XPhos).",
+    limitations="sp3-sp3 coupling difficult. β-Hydride elimination with alkyl halides. Protodeboronation can compete. Homo-coupling side reaction.",
+    mechanism="Oxidative addition → transmetalation (base-assisted) → reductive elimination. Pd(0)/Pd(II) cycle.",
+    refs="Miyaura, Suzuki, Chem. Rev. 1995, 95, 2457. Martin, Buchwald, Acc. Chem. Res. 2008, 41, 1461.",
+    related="Heck, Negishi, Stille, Kumada, Hiyama",
+    functional_groups="aryl halide, boronic acid, boronate ester")
+
+_nr("Heck Reaction",
+    aliases=["Mizoroki-Heck", "Heck coupling"],
+    category="C-C Bond Formation", type_="Cross-Coupling",
+    summary="Pd-catalyzed coupling of aryl/vinyl halides with alkenes to form substituted alkenes.",
+    conditions="Pd(OAc)2 or PdCl2 (1-5 mol%), ligand (PPh3 or P(o-tol)3), base (Et3N, K2CO3, NaOAc), DMF or DMA, 80-120°C.",
+    substrate="Aryl/vinyl halides + alkenes (electron-poor preferred). Regioselectivity: addition at less hindered end of alkene.",
+    limitations="Requires β-hydrogens on alkene. Regioselectivity can be problematic. Double bond isomerization possible.",
+    mechanism="Oxidative addition → syn-migratory insertion into alkene → β-hydride elimination. Pd(0)/Pd(II) cycle.",
+    refs="Heck, Nolley, J. Org. Chem. 1972, 37, 2320. Beletskaya, Cheprakov, Chem. Rev. 2000, 100, 3009.",
+    related="Suzuki, Negishi, Stille, Fujiwara-Moritani",
+    functional_groups="aryl halide, alkene")
+
+_nr("Negishi Coupling",
+    aliases=["Negishi reaction"],
+    category="C-C Bond Formation", type_="Cross-Coupling",
+    summary="Pd or Ni-catalyzed coupling of organozinc reagents with organic halides. Excellent functional group tolerance.",
+    conditions="Pd(PPh3)4 or Pd(dba)2/ligand, THF, 0°C to RT. Organozinc prepared from RLi or RMgX + ZnCl2.",
+    substrate="RZnX + R'X (X = I, Br, Cl, OTf). Works with sp, sp2, and sp3 centers. Tolerates esters, nitriles, ketones.",
+    limitations="Organozinc reagents are moisture-sensitive (less than Grignard). Requires preparation of organozinc species.",
+    mechanism="Oxidative addition → transmetalation → reductive elimination. Pd(0)/Pd(II) cycle.",
+    refs="Negishi, King, Okukado, J. Org. Chem. 1977, 42, 1821. Nobel Prize 2010.",
+    related="Suzuki, Stille, Kumada",
+    functional_groups="organozinc, aryl halide")
+
+_nr("Stille Coupling",
+    aliases=["Stille reaction", "Migita-Kosugi-Stille"],
+    category="C-C Bond Formation", type_="Cross-Coupling",
+    summary="Pd-catalyzed coupling of organostannanes (organotin) with organic halides. Very broad scope and excellent FG tolerance.",
+    conditions="Pd(PPh3)4 or Pd2(dba)3 + AsPh3 (1-5 mol%), DMF, toluene, or NMP, 50-100°C. CuI or CsF as additives improve rate.",
+    substrate="R3SnR' + R''X (X = I, Br, Cl, OTf). Works well with vinyl, aryl, acyl halides. Tolerates almost all functional groups.",
+    limitations="Toxicity of organotin compounds. Tin residues difficult to remove. Homo-coupling. Slow transmetalation sometimes.",
+    mechanism="Oxidative addition → transmetalation → reductive elimination. Pd(0)/Pd(II) cycle.",
+    refs="Stille, Angew. Chem. Int. Ed. 1986, 25, 508. Espinet, Echavarren, Angew. Chem. Int. Ed. 2004, 43, 4704.",
+    related="Suzuki, Negishi, Heck",
+    functional_groups="organostannane, aryl halide")
+
+_nr("Kumada Coupling",
+    aliases=["Kumada-Corriu", "Kumada reaction"],
+    category="C-C Bond Formation", type_="Cross-Coupling",
+    summary="Ni or Pd-catalyzed coupling of Grignard reagents with organic halides. First transition metal-catalyzed cross-coupling.",
+    conditions="NiCl2(dppf) or Pd(dppf)Cl2, THF or Et2O, 0°C to RT.",
+    substrate="RMgX + R'X. Works best for sp2-sp2 coupling.",
+    limitations="Limited FG tolerance (Grignard reacts with ketones, esters, etc.). Cannot use protic solvents.",
+    mechanism="Oxidative addition → transmetalation → reductive elimination.",
+    refs="Kumada, Tamao, Sumitani, J. Am. Chem. Soc. 1972, 94, 4374. Corriu, Masse, J. Chem. Soc. Chem. Commun. 1972, 144.",
+    related="Suzuki, Negishi, Grignard reaction",
+    functional_groups="Grignard reagent, aryl halide")
+
+_nr("Sonogashira Coupling",
+    aliases=["Sonogashira reaction"],
+    category="C-C Bond Formation", type_="Cross-Coupling",
+    summary="Pd/Cu-catalyzed coupling of terminal alkynes with aryl/vinyl halides to form aryl/vinyl alkynes.",
+    conditions="PdCl2(PPh3)2 (2-5 mol%), CuI (5-10 mol%), amine base (Et3N, iPr2NH, piperidine), THF or DMF, RT-80°C.",
+    substrate="Terminal alkynes + aryl/vinyl halides or triflates. I > Br > Cl reactivity.",
+    limitations="Glaser homo-coupling of alkyne (in presence of O2). Requires anhydrous/degassed conditions. Cu-free variants available.",
+    mechanism="Pd cycle: oxidative addition → transmetalation from Cu-acetylide → reductive elimination. Cu cycle: deprotonation of alkyne → Cu-acetylide formation.",
+    refs="Sonogashira, Tohda, Hagihara, Tetrahedron Lett. 1975, 4467. Chinchilla, Nájera, Chem. Rev. 2007, 107, 874.",
+    related="Suzuki, Heck, Cadiot-Chodkiewicz, Glaser",
+    functional_groups="terminal alkyne, aryl halide")
+
+_nr("Buchwald-Hartwig Amination",
+    aliases=["Buchwald-Hartwig", "Pd-catalyzed amination"],
+    category="C-N Bond Formation", type_="Cross-Coupling",
+    summary="Pd-catalyzed coupling of amines with aryl halides to form aryl amines (C-N bonds).",
+    conditions="Pd2(dba)3 or Pd(OAc)2 + bulky phosphine ligand (BINAP, XPhos, SPhos, RuPhos, BrettPhos, tBuXPhos), strong base (NaOtBu, Cs2CO3, K3PO4), toluene or dioxane, 80-110°C.",
+    substrate="Primary/secondary amines, amides, sulfonamides + aryl bromides/chlorides/triflates. Ligand choice critical for selectivity.",
+    limitations="Competitive β-hydride elimination with some substrates. Sensitive to steric effects. Ligand screening often necessary.",
+    mechanism="Oxidative addition → amine coordination/deprotonation → reductive elimination.",
+    refs="Guram, Buchwald, J. Am. Chem. Soc. 1994, 116, 7901. Louie, Hartwig, Tetrahedron Lett. 1995, 36, 3609.",
+    related="Ullmann coupling, Chan-Lam coupling, Goldberg reaction",
+    functional_groups="amine, aryl halide")
+
+_nr("Hiyama Coupling",
+    aliases=["Hiyama reaction"],
+    category="C-C Bond Formation", type_="Cross-Coupling",
+    summary="Pd-catalyzed coupling of organosilanes with organic halides. Uses inexpensive, non-toxic silicon reagents.",
+    conditions="Pd(0) catalyst, fluoride activator (TBAF, KF), THF or DMF, RT-80°C.",
+    substrate="Aryl/vinylsilanes (trialkoxysilanes, silanols) + aryl halides.",
+    limitations="Requires fluoride activation. Slower transmetalation than Sn, B, Zn. Competing protodesilylation.",
+    mechanism="Oxidative addition → fluoride-assisted transmetalation → reductive elimination.",
+    refs="Hatanaka, Hiyama, J. Org. Chem. 1988, 53, 918. Denmark, Sweis, Acc. Chem. Res. 2002, 35, 835.",
+    related="Suzuki, Stille, Negishi",
+    functional_groups="organosilane, aryl halide")
+
+# --- C-C Bond Formation: Classical ---
+
+_nr("Grignard Reaction",
+    aliases=["Grignard addition"],
+    category="C-C Bond Formation", type_="Addition",
+    summary="Addition of organomagnesium halides (RMgX) to electrophiles (carbonyls, epoxides, CO2, etc.).",
+    conditions="RMgX in THF or Et2O, add to electrophile at 0°C to -78°C, then warm. Requires anhydrous/inert atmosphere.",
+    substrate="RMgX + aldehydes → 2° alcohols; + ketones → 3° alcohols; + esters → 3° alcohols (2 equiv); + CO2 → carboxylic acids; + epoxides → alcohols.",
+    limitations="Incompatible with protic groups (OH, NH, COOH) and many electrophilic FGs. Cannot use protic solvents. Sensitive to moisture/air.",
+    mechanism="Nucleophilic addition. Schlenk equilibrium: 2 RMgX ⇌ R2Mg + MgX2.",
+    refs="Grignard, Compt. Rend. 1900, 130, 1322. Nobel Prize 1912.",
+    related="Organolithium, Barbier, Reformatsky, Kumada coupling",
+    functional_groups="organomagnesium, aldehyde, ketone, ester, epoxide")
+
+_nr("Aldol Reaction",
+    aliases=["Aldol condensation", "Aldol addition"],
+    category="C-C Bond Formation", type_="Addition",
+    summary="Addition of enolate or enol to aldehyde/ketone forming β-hydroxy carbonyl. Condensation gives α,β-unsaturated carbonyl.",
+    conditions="Base-catalyzed: LDA, NaOH, KOH; acid-catalyzed: BF3·Et2O, TiCl4. Mukaiyama aldol: silyl enol ether + Lewis acid.",
+    substrate="Enolizable carbonyl + aldehyde/ketone. Crossed aldol requires careful control (Evans auxiliary, Zimmerman-Traxler model).",
+    limitations="Self-condensation. Mixtures of syn/anti diastereomers without chiral auxiliary. Retro-aldol under harsh conditions.",
+    mechanism="Enolate formation → nucleophilic addition to carbonyl → β-hydroxy carbonyl. E1cb dehydration gives α,β-unsaturated product.",
+    refs="Mukaiyama, Org. React. 1982, 28, 203. Evans, Aldrichimica Acta 1982, 15, 23.",
+    related="Mukaiyama aldol, Claisen condensation, Reformatsky, Mannich",
+    functional_groups="enolate, aldehyde, ketone")
+
+_nr("Wittig Reaction",
+    aliases=["Wittig olefination"],
+    category="C-C Bond Formation", type_="Olefination",
+    summary="Reaction of phosphonium ylides with aldehydes/ketones to form alkenes with loss of Ph3P=O.",
+    conditions="Ylide from R3P+CH2R'X- + base (nBuLi, NaHMDS, KOtBu). Non-stabilized ylides: THF, -78°C. Stabilized ylides: RT.",
+    substrate="Phosphonium salt + aldehyde (or reactive ketone). Selectivity: non-stabilized ylides → Z-alkene; stabilized ylides → E-alkene.",
+    limitations="Removal of Ph3P=O can be difficult. E/Z selectivity not always predictable. Ketones react slowly. MW of phosphine oxide waste.",
+    mechanism="Ylide + carbonyl → betaine → oxaphosphetane → [2+2] cycloreversion → alkene + Ph3P=O.",
+    refs="Wittig, Geissler, Justus Liebigs Ann. Chem. 1953, 580, 44. Nobel Prize 1979. Maryanoff, Reitz, Chem. Rev. 1989, 89, 863.",
+    related="HWE, Julia olefination, Peterson olefination, Tebbe olefination",
+    functional_groups="phosphonium ylide, aldehyde, ketone")
+
+_nr("Horner-Wadsworth-Emmons Reaction",
+    aliases=["HWE", "HWE reaction", "Horner-Wadsworth-Emmons", "HWE olefination"],
+    category="C-C Bond Formation", type_="Olefination",
+    summary="Olefination using phosphonate-stabilized carbanions. More E-selective than Wittig; water-soluble byproduct.",
+    conditions="Phosphonate ester + base (NaH, LiHMDS, DBU) in THF, 0°C to RT. Still-Gennari modification for Z-selectivity.",
+    substrate="Phosphonate esters (Arbuzov product) + aldehydes. Excellent E-selectivity with standard conditions. Z-selective with Still-Gennari (CF3CH2O phosphonate + KHMDS/18-crown-6).",
+    limitations="Less reactive with ketones. Requires preparation of phosphonate ester.",
+    mechanism="Similar to Wittig but via open transition state. Phosphonate anion + aldehyde → β-hydroxyphosphonate → elimination.",
+    refs="Horner, Hoffmann, Wippel, Chem. Ber. 1958, 91, 61. Wadsworth, Emmons, J. Am. Chem. Soc. 1961, 83, 1733. Still, Gennari, Tetrahedron Lett. 1983, 24, 4405.",
+    related="Wittig, Julia olefination, Peterson",
+    functional_groups="phosphonate ester, aldehyde")
+
+_nr("Diels-Alder Reaction",
+    aliases=["[4+2] cycloaddition", "Diels-Alder"],
+    category="Cycloaddition", type_="Pericyclic",
+    summary="[4+2] cycloaddition of conjugated diene with dienophile to form cyclohexene. Concerted, stereospecific.",
+    conditions="Thermal. Lewis acid catalysis (AlCl3, BF3·Et2O, ZnCl2) accelerates and improves endo selectivity. Chiral Lewis acids for asymmetric DA.",
+    substrate="Diene (s-cis conformation, electron-rich preferred) + dienophile (electron-poor preferred). Normal electron demand: EDG-diene + EWG-dienophile. Inverse ED possible.",
+    limitations="Diene must adopt s-cis. Retro-DA at high temperature. Endo/exo selectivity. Hetero-DA possible with C=O, C=N dienophiles.",
+    mechanism="Concerted [4πs + 2πs] pericyclic reaction. Suprafacial-suprafacial. Endo rule (Alder rule). Woodward-Hoffmann allowed thermally.",
+    refs="Diels, Alder, Justus Liebigs Ann. Chem. 1928, 460, 98. Nobel Prize 1950. Nicolaou et al., Angew. Chem. Int. Ed. 2002, 41, 1668.",
+    related="Hetero-Diels-Alder, 1,3-dipolar cycloaddition, [2+2] cycloaddition, retro-Diels-Alder",
+    functional_groups="diene, dienophile")
+
+_nr("Mannich Reaction",
+    aliases=["Mannich condensation"],
+    category="C-C Bond Formation", type_="Multicomponent",
+    summary="Three-component reaction of aldehyde + amine + enolizable ketone to form β-amino carbonyl (Mannich base).",
+    conditions="Acid catalysis (AcOH, HCl). Formaldehyde + secondary amine + ketone in water/ethanol. Organocatalytic asymmetric versions available.",
+    substrate="Non-enolizable aldehyde (formaldehyde most common) + primary or secondary amine + enolizable carbonyl compound.",
+    limitations="Mixtures with unsymmetrical ketones. Double Mannich possible. Retro-Mannich under some conditions.",
+    mechanism="Iminium ion formation from aldehyde + amine → enol or enolate attacks iminium ion → β-amino carbonyl.",
+    refs="Mannich, Krösche, Arch. Pharm. 1912, 250, 647. Arend et al., Angew. Chem. Int. Ed. 1998, 37, 1044.",
+    related="Aldol, Strecker, Henry reaction",
+    functional_groups="aldehyde, amine, enol")
+
+_nr("Henry Reaction",
+    aliases=["Nitroaldol reaction", "Henry nitroaldol"],
+    category="C-C Bond Formation", type_="Addition",
+    summary="Base-catalyzed addition of nitroalkane to aldehyde/ketone giving β-nitro alcohol.",
+    conditions="Base (NaOH, K2CO3, DBU, guanidine). Asymmetric versions with Cu/BOX, rare earth catalysts.",
+    substrate="Nitroalkane (nitromethane most common) + aldehyde. NO2 group can be transformed: → amine (reduction), → carbonyl (Nef), → alkene (elimination).",
+    limitations="Retro-Henry possible. Elimination to nitroalkene can occur (useful or undesired). Mixtures of diastereomers.",
+    mechanism="Deprotonation of nitroalkane → nitronate anion attacks carbonyl.",
+    refs="Henry, Compt. Rend. 1895, 120, 1265. Luzzio, Tetrahedron 2001, 57, 915.",
+    related="Aldol, Nitro-Mannich, Nef reaction",
+    functional_groups="nitroalkane, aldehyde")
+
+_nr("Reformatsky Reaction",
+    aliases=["Reformatsky"],
+    category="C-C Bond Formation", type_="Addition",
+    summary="Zinc-mediated addition of α-haloesters to aldehydes/ketones giving β-hydroxy esters.",
+    conditions="α-Bromoester + Zn dust in THF or benzene, reflux. Sonication or activated Zn (Rieke Zn) helpful.",
+    substrate="α-Bromo ester + aldehyde/ketone. Better FG tolerance than Grignard due to lower reactivity of organozinc.",
+    limitations="Less reactive than Grignard. Sometimes sluggish initiation. Diastereoselectivity moderate.",
+    mechanism="Zn inserts into C-Br bond → organozinc enolate → addition to carbonyl.",
+    refs="Reformatsky, Ber. Dtsch. Chem. Ges. 1887, 20, 1210. Rathke, Org. React. 1975, 22, 423.",
+    related="Aldol, Grignard, Blaise reaction",
+    functional_groups="α-haloester, aldehyde, ketone, zinc")
+
+_nr("Baylis-Hillman Reaction",
+    aliases=["Morita-Baylis-Hillman", "MBH reaction"],
+    category="C-C Bond Formation", type_="Addition",
+    summary="Coupling of activated alkene (α,β-unsaturated carbonyl) with aldehyde in presence of nucleophilic catalyst (DABCO, PPh3).",
+    conditions="DABCO (5-100 mol%) or PPh3 in neat conditions or in solvent (DMSO, MeOH), RT. Often slow (days).",
+    substrate="Acrylate, MVK, acrylonitrile + aldehydes. Product is α-methylene-β-hydroxy ester/ketone.",
+    limitations="Very slow reaction rates (sometimes weeks). Can be accelerated with pressure or Lewis acid co-catalysts.",
+    mechanism="Nucleophilic catalyst adds to alkene → zwitterionic enolate → aldol with aldehyde → proton transfer → elimination of catalyst.",
+    refs="Baylis, Hillman, German Patent 2155113, 1972. Basavaiah et al., Chem. Rev. 2003, 103, 811.",
+    related="Aldol, Rawal Diels-Alder",
+    functional_groups="acrylate, aldehyde")
+
+# --- Olefinations ---
+
+_nr("Julia-Lythgoe Olefination",
+    aliases=["Julia olefination", "Julia-Lythgoe", "Modified Julia", "Julia-Kocienski"],
+    category="C-C Bond Formation", type_="Olefination",
+    summary="Olefination via sulfone chemistry. Classic Julia: phenylsulfone + aldehyde → β-hydroxy sulfone → reductive elimination → E-alkene. Modified Julia-Kocienski: one-pot using benzothiazolyl (BT) or tetrazolyl (PT) sulfones.",
+    conditions="Classic: PhSO2CHR + nBuLi + RCHO → β-hydroxy sulfone; then Na/Hg (or SmI2) + MeOH → E-alkene. Modified (Kocienski): BT/PT sulfone + KHMDS + RCHO, one pot, -78°C to RT.",
+    substrate="Sulfone + aldehyde. E-selective (classic). Modified Julia: E or Z depending on sulfone type.",
+    limitations="Classic requires two steps. Na(Hg) amalgam unpleasant. Modified Julia variable E/Z ratios.",
+    mechanism="Classic: addition → β-elimination (reductive). Modified: addition → Smiles rearrangement → SO2 loss.",
+    refs="Julia, Paris, Tetrahedron Lett. 1973, 14, 4833. Kocienski et al., Synlett 1998, 26.",
+    related="Wittig, HWE, Peterson olefination",
+    functional_groups="sulfone, aldehyde")
+
+_nr("Peterson Olefination",
+    aliases=["Peterson reaction"],
+    category="C-C Bond Formation", type_="Olefination",
+    summary="Olefination of aldehydes/ketones using α-silyl carbanions. Stereochemistry controlled by elimination conditions.",
+    conditions="α-Silyl carbanion (from TMSCH2Li or TMSCH2MgCl) + carbonyl. Acidic workup → E-alkene. Basic workup → Z-alkene.",
+    substrate="α-TMS organolithium/Grignard + aldehyde/ketone.",
+    limitations="Requires preparation of α-silyl organometallic.",
+    mechanism="Addition → β-hydroxy silane. Acid: anti-elimination (E). Base: syn-elimination via pentacoordinate Si (Z).",
+    refs="Peterson, J. Org. Chem. 1968, 33, 780.",
+    related="Wittig, HWE, Julia",
+    functional_groups="α-silyl carbanion, aldehyde, ketone")
+
+# --- Oxidations ---
+
+_nr("Swern Oxidation",
+    aliases=["Swern"],
+    category="Oxidation", type_="Alcohol → Aldehyde/Ketone",
+    summary="Oxidation of primary/secondary alcohols to aldehydes/ketones using DMSO/oxalyl chloride.",
+    conditions="(COCl)2 + DMSO in CH2Cl2 at -78°C, then add alcohol, then Et3N. Warm to RT.",
+    substrate="Primary → aldehyde (no over-oxidation). Secondary → ketone. Very mild, compatible with sensitive substrates.",
+    limitations="Must maintain -78°C during DMSO activation (explosive side products above -60°C). Generates CO, CO2, Me2S (stinky). Stoichiometric reagents.",
+    mechanism="DMSO activated by oxalyl chloride → chlorosulfonium salt. Alcohol attacks → alkoxysulfonium → Et3N-mediated intramolecular elimination → carbonyl + Me2S.",
+    refs="Omura, Swern, Tetrahedron 1978, 34, 1651. Mancuso, Swern, Synthesis 1981, 165.",
+    related="Dess-Martin, PCC, PDC, Ley (TPAP), Parikh-Doering, Pfitzner-Moffatt",
+    functional_groups="alcohol")
+
+_nr("Dess-Martin Periodinane",
+    aliases=["Dess-Martin", "DMP oxidation", "Dess-Martin oxidation"],
+    category="Oxidation", type_="Alcohol → Aldehyde/Ketone",
+    summary="Mild oxidation of alcohols using Dess-Martin periodinane (DMP). Very popular for sensitive substrates.",
+    conditions="1.1-1.5 equiv DMP in CH2Cl2, RT, 15-60 min. Add NaHCO3 for acid-sensitive substrates.",
+    substrate="Primary → aldehyde. Secondary → ketone. Tolerates many FGs including alkenes, alkynes, silyl ethers.",
+    limitations="Expensive reagent. Potentially explosive (contains I(V)). Shelf life limited. CH2Cl2 solvent usually required.",
+    mechanism="Ligand exchange on hypervalent iodine → reductive elimination → carbonyl + reduced iodine species.",
+    refs="Dess, Martin, J. Org. Chem. 1983, 48, 4155. Dess, Martin, J. Am. Chem. Soc. 1991, 113, 7277.",
+    related="Swern, PCC, TPAP, IBX",
+    functional_groups="alcohol")
+
+_nr("Jones Oxidation",
+    aliases=["Jones reagent", "CrO3/H2SO4"],
+    category="Oxidation", type_="Alcohol → Carboxylic Acid/Ketone",
+    summary="CrO3/H2SO4 in acetone. Oxidizes primary alcohols to carboxylic acids and secondary alcohols to ketones.",
+    conditions="Jones reagent (CrO3 in dilute H2SO4) in acetone, 0°C to RT. Titrate to persistent orange color.",
+    substrate="Primary alcohols → carboxylic acids. Secondary alcohols → ketones. Also oxidizes aldehydes to acids.",
+    limitations="Strong conditions — over-oxidation of 1° alcohols to acids. Not compatible with acid-sensitive groups. Generates toxic Cr waste.",
+    mechanism="Chromate ester formation → [2,3]-elimination.",
+    refs="Bowden, Heilbron, Jones, J. Chem. Soc. 1946, 39.",
+    related="PCC, PDC, Swern, Collins (CrO3·py2)",
+    functional_groups="alcohol, aldehyde")
+
+_nr("Sharpless Epoxidation",
+    aliases=["Sharpless AE", "SAE", "asymmetric epoxidation"],
+    category="Oxidation", type_="Asymmetric Epoxidation",
+    summary="Ti-catalyzed asymmetric epoxidation of allylic alcohols using TBHP and diethyl tartrate (DET).",
+    conditions="Ti(OiPr)4 (5-10 mol%), (+)- or (-)-DET or DIPT, TBHP, 4Å mol sieves, CH2Cl2, -20°C.",
+    substrate="Allylic alcohols. Predictable face selectivity from mnemonic: draw allylic OH at bottom-right → (+)-DET attacks from top, (-)-DET from bottom.",
+    limitations="Only works for allylic alcohols (OH directs). Non-allylic alkenes: use Jacobsen or Shi epoxidation. ee depends on alkene substitution pattern (trisubstituted best).",
+    mechanism="Ti-tartrate complex forms chiral pocket → TBHP delivers oxygen to one face of alkene.",
+    refs="Katsuki, Sharpless, J. Am. Chem. Soc. 1980, 102, 5974. Nobel Prize 2001.",
+    related="Jacobsen epoxidation, Shi epoxidation, Sharpless dihydroxylation",
+    functional_groups="allylic alcohol, alkene")
+
+_nr("Sharpless Dihydroxylation",
+    aliases=["Sharpless AD", "SAD", "asymmetric dihydroxylation", "AD-mix"],
+    category="Oxidation", type_="Asymmetric Dihydroxylation",
+    summary="Os-catalyzed asymmetric dihydroxylation of alkenes to syn-1,2-diols using AD-mix-α or AD-mix-β.",
+    conditions="AD-mix-α (contains (DHQ)2PHAL + K2OsO4·2H2O + K3Fe(CN)6 + K2CO3) or AD-mix-β (contains (DHQD)2PHAL). tBuOH/H2O 1:1, 0°C.",
+    substrate="Virtually any alkene. Mnemonic predicts face selectivity. Best ee with trans-disubstituted alkenes.",
+    limitations="Os is toxic and expensive (catalytic amounts mitigate). Terminal alkenes give lower ee. MeSO2NH2 accelerates slow substrates.",
+    mechanism="OsO4 + chiral amine ligand → [3+2] cycloaddition with alkene → osmate ester → hydrolysis → diol + Os(VI). Reoxidation by K3Fe(CN)6.",
+    refs="Jacobsen, Marko, Mungall, Sharpless, J. Am. Chem. Soc. 1988, 110, 1968. Nobel Prize 2001.",
+    related="Sharpless epoxidation, Upjohn dihydroxylation (OsO4/NMO), Sharpless aminohydroxylation",
+    functional_groups="alkene")
+
+_nr("Baeyer-Villiger Oxidation",
+    aliases=["Baeyer-Villiger", "BV oxidation"],
+    category="Oxidation", type_="Ketone → Ester/Lactone",
+    summary="Oxidation of ketone to ester (or cyclic ketone to lactone) using peracid. Migratory aptitude determines regiochemistry.",
+    conditions="mCPBA (1.1-3 equiv) in CH2Cl2, RT to reflux. Also: CF3CO3H, MMPP, H2O2/BF3.",
+    substrate="Cyclic ketones → lactones. Acyclic ketones → esters. Migratory aptitude: 3° alkyl > cyclohexyl > 2° alkyl > phenyl > 1° alkyl > methyl.",
+    limitations="Competing epoxidation if alkene present. mCPBA can be hazardous on scale. Acidic byproduct.",
+    mechanism="Nucleophilic addition of peracid to ketone → Criegee intermediate → 1,2-migration with loss of carboxylate.",
+    refs="Baeyer, Villiger, Ber. Dtsch. Chem. Ges. 1899, 32, 3625. Krow, Org. React. 1993, 43, 251.",
+    related="mCPBA epoxidation, Beckmann rearrangement",
+    functional_groups="ketone")
+
+_nr("Pinnick Oxidation",
+    aliases=["Pinnick", "Lindgren oxidation", "NaClO2 oxidation", "Kraus oxidation"],
+    category="Oxidation", type_="Aldehyde → Carboxylic Acid",
+    summary="Selective oxidation of aldehyde to carboxylic acid using NaClO2 (sodium chlorite). Does not affect alkenes, alkynes, or ketones.",
+    conditions="NaClO2 (2-5 equiv), NaH2PO4 (buffer), 2-methyl-2-butene (HOCl scavenger), tBuOH/H2O, RT.",
+    substrate="Aldehydes → carboxylic acids. Very chemoselective — alkenes, alcohols, ethers untouched.",
+    limitations="2-Methyl-2-butene scavenger essential (otherwise HOCl causes side reactions). Chlorine gas can evolve.",
+    mechanism="NaClO2 oxidizes aldehyde via chlorous acid. 2-Methyl-2-butene quenches HOCl byproduct.",
+    refs="Bal, Pinnick, Tetrahedron 1981, 37, 2091. Lindgren, Nilsson, Acta Chem. Scand. 1973, 27, 888.",
+    related="Jones, PDC, MnO2, TEMPO",
+    functional_groups="aldehyde")
+
+_nr("TEMPO Oxidation",
+    aliases=["TEMPO", "Anelli oxidation", "TEMPO/bleach"],
+    category="Oxidation", type_="Alcohol → Aldehyde",
+    summary="Catalytic TEMPO with stoichiometric co-oxidant selectively oxidizes primary alcohols to aldehydes.",
+    conditions="TEMPO (cat.), NaOCl (bleach) or PhI(OAc)2 or BAIB, CH2Cl2 or CH2Cl2/H2O biphasic. Zhao variant: TEMPO/BAIB/CH2Cl2.",
+    substrate="Primary alcohols → aldehydes (no over-oxidation to acid). Secondary alcohols → ketones. Chemoselective for 1° over 2°.",
+    limitations="Not effective for hindered secondary alcohols. Some substrates require different co-oxidant.",
+    mechanism="Oxoammonium cation is active oxidant. TEMPO → oxoammonium → hydroxylamine (recycled by co-oxidant).",
+    refs="Anelli et al., J. Org. Chem. 1987, 52, 2559. De Mico et al., J. Org. Chem. 1997, 62, 6974.",
+    related="Swern, Dess-Martin, PCC, Ley (TPAP)",
+    functional_groups="primary alcohol")
+
+_nr("Ley Oxidation",
+    aliases=["TPAP", "TPAP/NMO", "Ley-Griffith"],
+    category="Oxidation", type_="Alcohol → Aldehyde/Ketone",
+    summary="Catalytic TPAP (Pr4N+ RuO4-) with NMO as co-oxidant. Mild, selective, good for sensitive substrates.",
+    conditions="TPAP (2-5 mol%), NMO (1.5 equiv), 4Å mol sieves, CH2Cl2, RT.",
+    substrate="Primary → aldehyde. Secondary → ketone. Excellent chemoselectivity.",
+    limitations="Sensitive to scale (exothermic). Molecular sieves essential. Can be sluggish with hindered substrates.",
+    mechanism="Ru(VII) → Ru(V) during oxidation, regenerated by NMO.",
+    refs="Ley et al., Synthesis 1994, 639. Griffith et al., J. Chem. Soc. Chem. Commun. 1987, 1625.",
+    related="Swern, Dess-Martin, TEMPO",
+    functional_groups="alcohol")
+
+_nr("Ozonolysis",
+    aliases=["Ozonolysis", "Criegee mechanism"],
+    category="Oxidation", type_="Alkene Cleavage",
+    summary="Cleavage of C=C double bonds with ozone to give aldehydes/ketones (reductive workup) or carboxylic acids (oxidative workup).",
+    conditions="O3 bubbled through substrate in CH2Cl2 or MeOH at -78°C until blue color persists. Reductive workup: Me2S or PPh3. Oxidative workup: H2O2.",
+    substrate="Any alkene. Product depends on substitution pattern and workup. Reductive: aldehydes/ketones. Oxidative: carboxylic acids/ketones.",
+    limitations="O3 is toxic and generated on-site. Must quench peroxidic intermediates. Scale-up safety concerns.",
+    mechanism="[3+2] cycloaddition → molozonide → retro-[3+2] → carbonyl + carbonyl oxide → [3+2] → ozonide. Workup cleaves ozonide.",
+    refs="Criegee, Angew. Chem. Int. Ed. 1975, 14, 745.",
+    related="Lemieux-Johnson (OsO4/NaIO4), dihydroxylation/periodate",
+    functional_groups="alkene")
+
+_nr("Wacker Oxidation",
+    aliases=["Wacker process", "Wacker-Tsuji"],
+    category="Oxidation", type_="Alkene → Ketone",
+    summary="Pd(II)-catalyzed oxidation of terminal alkenes to methyl ketones (Markovnikov).",
+    conditions="PdCl2 (10 mol%), CuCl (co-oxidant), O2, DMF/H2O, RT-60°C.",
+    substrate="Terminal alkenes → methyl ketones. Anti-Markovnikov selectivity possible with specific ligands.",
+    limitations="Internal alkenes unreactive. Can give aldehyde byproduct. Over-oxidation possible.",
+    mechanism="Pd(II) coordinates alkene → nucleophilic attack of water (Markovnikov) → β-hydride elimination → enol → ketone. Pd(0) reoxidized by CuCl2/O2.",
+    refs="Smidt et al., Angew. Chem. 1959, 71, 176. Tsuji, Synthesis 1984, 369.",
+    related="Heck, hydroboration-oxidation",
+    functional_groups="terminal alkene")
+
+# --- Reductions ---
+
+_nr("Birch Reduction",
+    aliases=["Birch"],
+    category="Reduction", type_="Aromatic → 1,4-Cyclohexadiene",
+    summary="Dissolving metal reduction of aromatic rings to 1,4-cyclohexadienes using Na/Li in NH3(l) + alcohol.",
+    conditions="Na or Li metal in liquid NH3 (-33°C) with tBuOH or iPrOH as proton source. THF co-solvent.",
+    substrate="Arenes. EDG (OMe, NR2): 2,5-diene (unconjugated). EWG (COOH, COOR): 1,4-diene (conjugated with EWG).",
+    limitations="Requires liquid NH3 (hazardous). Over-reduction possible. Na/NH3 incompatible with many FGs (halides, epoxides).",
+    mechanism="Solvated electrons reduce aromatic ring → radical anion → protonation → radical → second electron → carbanion → protonation.",
+    refs="Birch, J. Chem. Soc. 1944, 430. Rabideau, Marcinow, Org. React. 1992, 42, 1.",
+    related="Benkeser reduction, catalytic hydrogenation",
+    functional_groups="arene")
+
+_nr("Wolff-Kishner Reduction",
+    aliases=["Wolff-Kishner", "Huang-Minlon modification"],
+    category="Reduction", type_="Carbonyl → Methylene",
+    summary="Reduction of aldehydes/ketones to alkanes via hydrazone formation and base-mediated N2 loss.",
+    conditions="Hydrazine (NH2NH2) + KOH in ethylene glycol (or diethylene glycol), reflux (200°C). Huang-Minlon: one-pot.",
+    substrate="Aldehydes/ketones → CH2. Complementary to Clemmensen (acidic conditions).",
+    limitations="High temperatures. Base-sensitive groups not tolerated. Long reaction times. Not for acid-sensitive substrates (use this instead of Clemmensen).",
+    mechanism="Hydrazone formation → deprotonation by base → carbanion → loss of N2 → protonation → alkane.",
+    refs="Wolff, Justus Liebigs Ann. Chem. 1912, 394, 86. Kishner, J. Russ. Phys. Chem. Soc. 1911, 43, 582. Huang-Minlon, J. Am. Chem. Soc. 1946, 68, 2487.",
+    related="Clemmensen reduction, thioacetal/Raney Ni desulfurization",
+    functional_groups="aldehyde, ketone")
+
+_nr("Clemmensen Reduction",
+    aliases=["Clemmensen"],
+    category="Reduction", type_="Carbonyl → Methylene",
+    summary="Reduction of aldehydes/ketones to alkanes using Zn(Hg)/conc. HCl. Acidic complement to Wolff-Kishner.",
+    conditions="Zn(Hg) amalgam, concentrated HCl, reflux.",
+    substrate="Aryl ketones → aryl alkanes. Particularly useful for Friedel-Crafts acylation products.",
+    limitations="Strong acid conditions. Not suitable for acid-sensitive substrates. Base-sensitive substrates OK (complement to W-K).",
+    mechanism="Heterogeneous — exact mechanism debated. Occurs on zinc surface. Not via alcohol intermediate.",
+    refs="Clemmensen, Ber. Dtsch. Chem. Ges. 1913, 46, 1837.",
+    related="Wolff-Kishner, thioacetal reduction",
+    functional_groups="aldehyde, ketone")
+
+_nr("Luche Reduction",
+    aliases=["Luche", "NaBH4/CeCl3"],
+    category="Reduction", type_="Selective 1,2-Reduction",
+    summary="CeCl3-mediated NaBH4 reduction. Selectively reduces ketones (1,2-addition) in presence of conjugated enones.",
+    conditions="CeCl3·7H2O (1.1 equiv) + NaBH4 (0.5-1 equiv) in MeOH, 0°C to RT.",
+    substrate="α,β-Unsaturated ketones → allylic alcohols (1,2-reduction). Highly selective over 1,4-reduction.",
+    limitations="MeOH solvent required. CeCl3 must be dry for some applications.",
+    mechanism="Ce(III) activates carbonyl toward 1,2-attack. NaBH4 provides hydride. Hard-hard interaction favored.",
+    refs="Luche, J. Am. Chem. Soc. 1978, 100, 2226. Gemal, Luche, J. Am. Chem. Soc. 1981, 103, 5454.",
+    related="NaBH4, L-Selectride, CBS reduction, DIBAL",
+    functional_groups="enone, ketone")
+
+_nr("CBS Reduction",
+    aliases=["Corey-Bakshi-Shibata", "CBS", "oxazaborolidine"],
+    category="Reduction", type_="Asymmetric Ketone Reduction",
+    summary="Enantioselective reduction of prochiral ketones using chiral oxazaborolidine catalyst and BH3.",
+    conditions="(R) or (S)-CBS catalyst (5-20 mol%) + BH3·THF or BH3·SMe2, toluene or THF, -20°C to RT.",
+    substrate="Prochiral ketones → chiral secondary alcohols. Predictable stereochemistry via transition state model.",
+    limitations="Requires stoichiometric BH3. Sensitive to moisture. Catalyst can be expensive.",
+    mechanism="Oxazaborolidine activates both BH3 (Lewis acid on B) and ketone → six-membered TS → enantioselective hydride delivery.",
+    refs="Corey, Bakshi, Shibata, J. Am. Chem. Soc. 1987, 109, 5551.",
+    related="Luche, Noyori hydrogenation, Alpine-Borane, DIP-Chloride",
+    functional_groups="ketone")
+
+# --- Rearrangements ---
+
+_nr("Claisen Rearrangement",
+    aliases=["Claisen", "oxy-Cope", "Ireland-Claisen", "Johnson-Claisen", "Eschenmoser-Claisen"],
+    category="Rearrangement", type_="[3,3]-Sigmatropic",
+    summary="[3,3]-Sigmatropic rearrangement of allyl vinyl ethers to γ,δ-unsaturated carbonyls. Many variants.",
+    conditions="Thermal: 150-250°C (aromatic Claisen) or RT-80°C (aliphatic with activation). Ireland-Claisen: LDA/TMSCl then warm. Johnson-Claisen: CH3C(OEt)3, cat. acid.",
+    substrate="Allyl vinyl ether → γ,δ-unsaturated carbonyl. Chair-like TS gives predictable stereochemistry (E-enolate → anti product).",
+    limitations="High temperatures for unactivated substrates. Requires allyl vinyl ether synthesis.",
+    mechanism="Concerted [3,3]-sigmatropic shift through chair-like transition state. Suprafacial.",
+    refs="Claisen, Ber. Dtsch. Chem. Ges. 1912, 45, 3157. Ireland, Mueller, Willard, J. Am. Chem. Soc. 1976, 98, 2868.",
+    related="Cope, oxy-Cope, [2,3]-Wittig, Overman",
+    functional_groups="allyl vinyl ether")
+
+_nr("Beckmann Rearrangement",
+    aliases=["Beckmann"],
+    category="Rearrangement", type_="Oxime → Amide",
+    summary="Rearrangement of oximes to amides (or lactams from cyclic ketoximes) under acidic conditions.",
+    conditions="Acid catalyst: H2SO4, PCl5, SOCl2, TsCl/base, Beckmann mixture (AcOH/HCl/Ac2O). Heat.",
+    substrate="Ketoximes → amides. Cyclic ketoximes → lactams (e.g., cyclohexanone oxime → caprolactam for nylon-6). Anti-periplanar group migrates.",
+    limitations="Regioselectivity: anti group migrates (E/Z of oxime determines product). Strong acid conditions.",
+    mechanism="Protonation of OH → loss of water → migration of anti group → nitrilium ion → water attack → amide.",
+    refs="Beckmann, Ber. Dtsch. Chem. Ges. 1886, 19, 988. Gawley, Org. React. 1988, 35, 1.",
+    related="Baeyer-Villiger, Curtius, Hofmann, Schmidt",
+    functional_groups="oxime, ketone")
+
+_nr("Curtius Rearrangement",
+    aliases=["Curtius degradation"],
+    category="Rearrangement", type_="Acyl Azide → Isocyanate",
+    summary="Thermal rearrangement of acyl azides to isocyanates (which can be trapped as amines, carbamates, or ureas).",
+    conditions="Acyl azide heated in inert solvent (toluene, 80-110°C). Modern: DPPA + Et3N generates acyl azide in situ. Trap with ROH → carbamate, H2O → amine, RNH2 → urea.",
+    substrate="Carboxylic acids → amines (one carbon shorter). Via: RCOOH → RCOCl → RCON3 → RNCO → RNH2.",
+    limitations="Acyl azides are potentially explosive. DPPA method much safer. HN3 generation possible.",
+    mechanism="Concerted 1,2-shift with loss of N2 from acyl azide → isocyanate.",
+    refs="Curtius, Ber. Dtsch. Chem. Ges. 1890, 23, 3023. Shioiri, Ninomiya, Yamada, J. Am. Chem. Soc. 1972, 94, 6203 (DPPA).",
+    related="Hofmann, Lossen, Schmidt, Wolff rearrangement",
+    functional_groups="acyl azide, carboxylic acid")
+
+# --- Key Named Reactions ---
+
+_nr("Mitsunobu Reaction",
+    aliases=["Mitsunobu"],
+    category="Substitution", type_="SN2 with Inversion",
+    summary="Converts ROH + HNu → RNu with inversion (SN2) using PPh3/DIAD (or DEAD). Converts alcohols to esters, ethers, amines, azides, etc.",
+    conditions="PPh3 (1.1 equiv), DIAD or DEAD (1.1 equiv), nucleophile (pKa < 11 for pronucleophile), THF, 0°C to RT.",
+    substrate="Secondary alcohols → inverted product. Primary alcohols work but no stereo consequence. Nucleophiles: carboxylic acids, phenols, phthalimide, HN3, sulfonamides.",
+    limitations="pKa requirement for pronucleophile (< 11-13). Stoichiometric PPh3/DIAD waste (difficult to remove). Triphenylphosphine oxide byproduct.",
+    mechanism="PPh3 + DIAD → betaine → activates alcohol (oxyphosphonium) → SN2 by nucleophile → inversion.",
+    refs="Mitsunobu, Yamada, Bull. Chem. Soc. Jpn. 1967, 40, 2380. Mitsunobu, Synthesis 1981, 1.",
+    related="Appel reaction, Williamson ether synthesis, Gabriel synthesis",
+    functional_groups="alcohol, carboxylic acid, phenol")
+
+_nr("Appel Reaction",
+    aliases=["Appel"],
+    category="Substitution", type_="OH → Halide",
+    summary="Conversion of alcohols to alkyl halides using PPh3/CX4 (X = Cl, Br). Inversion of stereochemistry.",
+    conditions="PPh3 + CBr4 (→ RBr) or CCl4 (→ RCl) in CH2Cl2, 0°C to RT.",
+    substrate="Primary and secondary alcohols → alkyl halides with inversion.",
+    limitations="Stoichiometric PPh3 waste. Ph3P=O removal. Side reactions with tertiary alcohols.",
+    mechanism="PPh3 + CX4 → [Ph3PX]+ + CHX3- → alcohol attacks P → oxyphosphonium → SN2 by halide.",
+    refs="Appel, Angew. Chem. Int. Ed. 1975, 14, 801.",
+    related="Mitsunobu, HBr, SOCl2, PBr3",
+    functional_groups="alcohol")
+
+_nr("Williamson Ether Synthesis",
+    aliases=["Williamson"],
+    category="Substitution", type_="SN2 Ether Formation",
+    summary="SN2 reaction of alkoxide with alkyl halide to form ethers.",
+    conditions="ROH + NaH (or KOH) → RO⁻; then add R'X (primary halide/tosylate), THF or DMF, 0°C to RT.",
+    substrate="Alkoxide + primary (or methyl) alkyl halide. Secondary halides → elimination competes.",
+    limitations="SN2 mechanism: primary halides work best. Secondary/tertiary → E2 elimination. Requires strong base to form alkoxide.",
+    mechanism="Deprotonation → alkoxide → SN2 on alkyl halide → ether.",
+    refs="Williamson, J. Chem. Soc. 1852, 4, 229.",
+    related="Mitsunobu, Ullmann ether synthesis",
+    functional_groups="alcohol, alkyl halide")
+
+_nr("Gabriel Synthesis",
+    aliases=["Gabriel"],
+    category="Substitution", type_="Primary Amine Synthesis",
+    summary="Synthesis of primary amines from alkyl halides using potassium phthalimide, avoiding over-alkylation.",
+    conditions="Potassium phthalimide + RX (primary halide) in DMF, RT-80°C → N-alkylphthalimide → hydrazinolysis (N2H4, Ing-Manske) or acid hydrolysis → primary amine.",
+    substrate="Primary alkyl halides → primary amines. Avoids polyalkylation problem of direct NH3 alkylation.",
+    limitations="Only for primary amines. SN2 conditions (no tertiary/neopentyl halides). Hydrazinolysis step required.",
+    mechanism="SN2 of phthalimide anion on alkyl halide. Deprotection by hydrazinolysis or acid.",
+    refs="Gabriel, Ber. Dtsch. Chem. Ges. 1887, 20, 2224.",
+    related="Staudinger reduction (azide → amine), reductive amination, Curtius",
+    functional_groups="alkyl halide, amine")
+
+_nr("Olefin Metathesis",
+    aliases=["Grubbs metathesis", "RCM", "ring-closing metathesis", "cross metathesis", "CM", "ROMP"],
+    category="C-C Bond Formation", type_="Metathesis",
+    summary="Redistribution of alkene fragments catalyzed by Ru or Mo carbene complexes. Includes RCM, CM, and ROMP.",
+    conditions="Grubbs I (PCy3)2Cl2Ru=CHPh, Grubbs II (IMes)(PCy3)Cl2Ru=CHPh, Hoveyda-Grubbs II. CH2Cl2 or toluene, RT-40°C, often under N2.",
+    substrate="RCM: dienes → cyclic alkenes (5-7 membered rings best). CM: two alkenes → cross product. ROMP: cyclic olefins → polymers.",
+    limitations="E/Z selectivity in CM. Ru contamination of products. Catalyst poisoning by amines, thiols, phosphines. Ethylene removal drives equilibrium.",
+    mechanism="Chauvin mechanism: [2+2] cycloaddition/cycloreversion between metal carbene and alkene → metallacyclobutane → products.",
+    refs="Grubbs, Handbook of Metathesis, 2003. Nobel Prize 2005 (Grubbs, Schrock, Chauvin).",
+    related="Wittig, HWE, Julia",
+    functional_groups="alkene")
+
+_nr("Click Chemistry",
+    aliases=["CuAAC", "Huisgen cycloaddition", "azide-alkyne cycloaddition", "click reaction"],
+    category="Cycloaddition", type_="1,3-Dipolar Cycloaddition",
+    summary="Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) to form 1,4-disubstituted 1,2,3-triazoles regioselectively.",
+    conditions="CuSO4·5H2O (5-10 mol%) + sodium ascorbate (reductant), tBuOH/H2O, RT. Or: CuI + DIPEA.",
+    substrate="Organic azide + terminal alkyne → 1,4-triazole. SPAAC (strain-promoted): no Cu needed with cyclooctynes.",
+    limitations="Requires terminal alkyne (internal alkynes unreactive). Cu toxicity in biological applications (use SPAAC). Azide safety (small organic azides can be explosive).",
+    mechanism="Cu(I) forms copper acetylide → coordinates azide → stepwise cycloaddition → regioselective 1,4-triazole.",
+    refs="Rostovtsev, Green, Fokin, Sharpless, Angew. Chem. Int. Ed. 2002, 41, 2596. Meldal, Tornøe, Chem. Rev. 2008, 108, 2952.",
+    related="Huisgen 1,3-dipolar cycloaddition, Diels-Alder",
+    functional_groups="azide, terminal alkyne, triazole")
+
+_nr("Strecker Synthesis",
+    aliases=["Strecker"],
+    category="C-C Bond Formation", type_="Multicomponent",
+    summary="Three-component synthesis of α-amino acids from aldehyde + amine (or NH3) + HCN. Gives α-aminonitrile → hydrolysis → amino acid.",
+    conditions="RCHO + NH4Cl + NaCN in H2O, RT. Or: RCHO + amine + TMSCN + Lewis acid catalyst.",
+    substrate="Aldehydes + amines + cyanide source → α-aminonitriles → α-amino acids (after hydrolysis).",
+    limitations="HCN toxicity. Racemic (asymmetric Strecker with chiral catalysts available). Hydrolysis step needed.",
+    mechanism="Aldehyde + amine → imine → cyanide addition to imine → α-aminonitrile.",
+    refs="Strecker, Justus Liebigs Ann. Chem. 1850, 75, 27.",
+    related="Mannich, Ugi, Passerini",
+    functional_groups="aldehyde, amine, cyanide")
+
+_nr("Ugi Reaction",
+    aliases=["Ugi four-component reaction", "Ugi 4CR"],
+    category="C-C Bond Formation", type_="Multicomponent",
+    summary="Four-component condensation of aldehyde + amine + carboxylic acid + isocyanide → α-acylamino amide.",
+    conditions="Mix all four components in MeOH, RT, 24-48h. High atom economy.",
+    substrate="Aldehyde + primary amine + carboxylic acid + isocyanide. Enormous diversity — combinatorial chemistry workhorse.",
+    limitations="Diastereoselectivity control difficult. Product often requires further cyclization/functionalization.",
+    mechanism="Imine formation → protonation by acid → α-addition of isocyanide → acyl migration (Mumm rearrangement) → product.",
+    refs="Ugi, Steinbrückner, Angew. Chem. 1960, 72, 267. Dömling, Ugi, Angew. Chem. Int. Ed. 2000, 39, 3168.",
+    related="Strecker, Passerini, Mannich, Biginelli",
+    functional_groups="aldehyde, amine, carboxylic acid, isocyanide")
+
+_nr("Sandmeyer Reaction",
+    aliases=["Sandmeyer"],
+    category="Substitution", type_="Diazonium → Halide/CN/etc.",
+    summary="Conversion of aryl diazonium salts to aryl halides (Cl, Br, I), cyanides, or other groups via Cu(I) catalysis.",
+    conditions="ArNH2 + NaNO2/HCl (0°C) → ArN2+. Then: CuCl → ArCl; CuBr → ArBr; CuCN → ArCN; KI → ArI (no Cu needed).",
+    substrate="Aryl amines → aryl halides, nitriles, and other derivatives via diazonium chemistry.",
+    limitations="Diazonium salts can be explosive (especially dry). Must keep cold. Yields sometimes moderate.",
+    mechanism="Single electron transfer from Cu(I) → aryl radical + N2 + Cu(II) → radical rebound with halide.",
+    refs="Sandmeyer, Ber. Dtsch. Chem. Ges. 1884, 17, 1633.",
+    related="Balz-Schiemann (→ ArF), Meerwein arylation, Schiemann",
+    functional_groups="aryl amine, diazonium salt")
+
+_nr("Fischer Esterification",
+    aliases=["Fischer ester synthesis", "acid-catalyzed esterification"],
+    category="Functional Group Interconversion", type_="Acid + Alcohol → Ester",
+    summary="Acid-catalyzed esterification of carboxylic acid with alcohol. Equilibrium reaction — drive with excess alcohol or remove water.",
+    conditions="RCOOH + R'OH, cat. H2SO4 or p-TsOH, reflux with Dean-Stark trap or molecular sieves.",
+    substrate="Carboxylic acids + primary/secondary alcohols → esters. Equilibrium favored by excess of one reactant or water removal.",
+    limitations="Equilibrium — reversible. Slow with bulky substrates. Tertiary alcohols → elimination instead.",
+    mechanism="Protonation of C=O → nucleophilic addition of alcohol → proton transfer → loss of water → ester.",
+    refs="Fischer, Speier, Ber. Dtsch. Chem. Ges. 1895, 28, 3252.",
+    related="Steglich, Yamaguchi, Mukaiyama, DCC coupling",
+    functional_groups="carboxylic acid, alcohol")
+
+_nr("Steglich Esterification",
+    aliases=["DCC coupling", "Steglich"],
+    category="Functional Group Interconversion", type_="Acid + Alcohol → Ester",
+    summary="DCC (or EDC)-mediated esterification with DMAP catalyst. Mild conditions for sensitive substrates.",
+    conditions="RCOOH + R'OH + DCC (1.1 equiv) + DMAP (cat., 5-20 mol%), CH2Cl2, 0°C to RT.",
+    substrate="Carboxylic acids + alcohols (including hindered). Also for amide bond formation (peptide coupling with HOBt).",
+    limitations="Dicyclohexylurea (DCU) byproduct can be hard to remove. Racemization possible with amino acids (add HOBt). EDC gives water-soluble urea (easier removal).",
+    mechanism="DCC activates acid → O-acylisourea → DMAP catalysis via acylpyridinium → nucleophilic substitution by alcohol.",
+    refs="Neises, Steglich, Angew. Chem. Int. Ed. 1978, 17, 522.",
+    related="Fischer, Yamaguchi, Mukaiyama esterification, amide coupling",
+    functional_groups="carboxylic acid, alcohol")
+
+_nr("Corey-Fuchs Reaction",
+    aliases=["Corey-Fuchs"],
+    category="C-C Bond Formation", type_="Aldehyde → Alkyne",
+    summary="Two-step conversion of aldehyde to terminal alkyne via gem-dibromo olefin intermediate.",
+    conditions="Step 1: RCHO + CBr4 + PPh3 → RCH=CBr2. Step 2: 2 equiv nBuLi, THF, -78°C → RC≡CH (or RC≡CLi for trapping).",
+    substrate="Aldehydes → terminal alkynes (one carbon homologation).",
+    limitations="Stoichiometric PPh3/CBr4 in step 1. Strong base (nBuLi) in step 2.",
+    mechanism="Step 1: Wittig-type. Step 2: deprotonation + α-elimination → vinylidene carbene → rearrangement → alkyne.",
+    refs="Corey, Fuchs, Tetrahedron Lett. 1972, 13, 3769.",
+    related="Seyferth-Gilbert/Ohira-Bestmann, Wittig",
+    functional_groups="aldehyde, alkyne")
+
+_nr("Ohira-Bestmann Reagent",
+    aliases=["Ohira-Bestmann", "Seyferth-Gilbert homologation", "dimethyl-1-diazo-2-oxopropylphosphonate"],
+    category="C-C Bond Formation", type_="Aldehyde → Alkyne",
+    summary="One-pot conversion of aldehyde to terminal alkyne using dimethyl-1-diazo-2-oxopropylphosphonate + K2CO3/MeOH.",
+    conditions="Ohira-Bestmann reagent + K2CO3, MeOH, RT, 12-24h. Much milder than Corey-Fuchs.",
+    substrate="Aldehydes → terminal alkynes. Tolerates many FGs.",
+    limitations="Reagent preparation (from dimethyl-2-oxopropylphosphonate + TsN3). Only works with aldehydes (not ketones).",
+    mechanism="HWE/Wittig-like → diazo intermediate → Wolff rearrangement → vinylidene carbene → 1,2-H shift → alkyne.",
+    refs="Ohira, Synth. Commun. 1989, 19, 561. Müller, Liepold, Bestmann, Synlett 1996, 521.",
+    related="Corey-Fuchs, Seyferth-Gilbert",
+    functional_groups="aldehyde, alkyne")
+
+_nr("Staudinger Reduction",
+    aliases=["Staudinger"],
+    category="Reduction", type_="Azide → Amine",
+    summary="Reduction of organic azides to primary amines using triphenylphosphine.",
+    conditions="RN3 + PPh3, THF/H2O, RT. Iminophosphorane intermediate hydrolyzed to amine.",
+    substrate="Alkyl/aryl azides → primary amines. Staudinger ligation (no hydrolysis): used in bioconjugation.",
+    limitations="Stoichiometric PPh3 (Ph3P=O waste). Azide must be accessible.",
+    mechanism="PPh3 attacks terminal N of azide → phosphazide → loss of N2 → iminophosphorane → hydrolysis → amine + Ph3P=O.",
+    refs="Staudinger, Meyer, Helv. Chim. Acta 1919, 2, 635.",
+    related="Hydrogenation (Pd/C, H2), Gabriel synthesis, Curtius",
+    functional_groups="azide, amine")
+
+_nr("Arndt-Eistert Homologation",
+    aliases=["Arndt-Eistert"],
+    category="Homologation", type_="Acid → Homologated Acid",
+    summary="One-carbon homologation of carboxylic acids via diazoketone and Wolff rearrangement.",
+    conditions="RCOOH → RCOCl (SOCl2) → RCOCHN2 (CH2N2) → Ag2O/H2O or hv → RCH2COOH.",
+    substrate="Carboxylic acids → one-carbon-homologated acids (or esters, amides if trapped with ROH, RNH2).",
+    limitations="Diazomethane is toxic, explosive, carcinogenic. Silver catalysis needed. TMS-diazomethane as safer alternative.",
+    mechanism="Wolff rearrangement: diazoketone → ketocarbene → ketene (1,2-shift) → trapping by nucleophile.",
+    refs="Arndt, Eistert, Ber. Dtsch. Chem. Ges. 1935, 68, 200.",
+    related="Corey-Fuchs, Curtius, Wolff rearrangement",
+    functional_groups="carboxylic acid, diazoketone")
+
+_nr("Finkelstein Reaction",
+    aliases=["Finkelstein"],
+    category="Substitution", type_="Halide Exchange",
+    summary="SN2 halide exchange: RCl/RBr + NaI → RI + NaCl/NaBr. Driven by precipitation of NaCl/NaBr in acetone.",
+    conditions="RX + NaI (excess) in acetone, reflux. NaCl/NaBr precipitate (insoluble in acetone) drives equilibrium.",
+    substrate="Primary alkyl chlorides/bromides → iodides. Classic example of Le Chatelier's principle.",
+    limitations="Only works well in acetone (NaCl/NaBr insoluble). Primarily for primary substrates (SN2).",
+    mechanism="SN2: iodide attacks carbon, halide leaves.",
+    refs="Finkelstein, Ber. Dtsch. Chem. Ges. 1910, 43, 1528.",
+    related="Appel, Williamson",
+    functional_groups="alkyl halide")
+
+_nr("Reductive Amination",
+    aliases=["reductive amination"],
+    category="C-N Bond Formation", type_="Carbonyl + Amine → Amine",
+    summary="Formation of C-N bond by condensation of carbonyl with amine followed by in situ reduction of imine/iminium.",
+    conditions="RCHO or R2CO + R'NH2 → imine → NaBH3CN or NaBH(OAc)3 (pH 6-7) → amine. One-pot or stepwise.",
+    substrate="Aldehydes (more reactive) or ketones + primary/secondary amines → secondary/tertiary amines.",
+    limitations="NaBH3CN: toxic (HCN generation in acid). NaBH(OAc)3: milder, preferred. Competing carbonyl reduction. Ketones slower than aldehydes.",
+    mechanism="Condensation → imine (or iminium ion) → hydride reduction → amine.",
+    refs="Borch, Bernstein, Durst, J. Am. Chem. Soc. 1971, 93, 2897. Abdel-Magid et al., J. Org. Chem. 1996, 61, 3849.",
+    related="Gabriel, Leuckart-Wallach, Eschweiler-Clarke, Mannich",
+    functional_groups="aldehyde, ketone, amine")
+
+_nr("Friedel-Crafts Alkylation",
+    aliases=["Friedel-Crafts alkylation", "FC alkylation"],
+    category="C-C Bond Formation", type_="Electrophilic Aromatic Substitution",
+    summary="Lewis acid-catalyzed alkylation of aromatic rings with alkyl halides, alkenes, or alcohols.",
+    conditions="ArH + RCl + AlCl3 (>1 equiv) in CH2Cl2 or CS2, 0°C to RT. Other Lewis acids: FeCl3, BF3·Et2O, ZnCl2.",
+    substrate="Electron-rich arenes + alkyl halides/alkenes. Product is activated → polyalkylation common.",
+    limitations="Over-alkylation (product more reactive than starting material). Carbocation rearrangements. Deactivated arenes unreactive. Not for arenes with NH2, NHR, OH (they coordinate to Lewis acid).",
+    mechanism="Lewis acid generates carbocation from RX → electrophilic aromatic substitution → arenium ion → deprotonation.",
+    refs="Friedel, Crafts, Compt. Rend. 1877, 84, 1392.",
+    related="Friedel-Crafts acylation, Blanc chloromethylation",
+    functional_groups="arene, alkyl halide")
+
+_nr("Friedel-Crafts Acylation",
+    aliases=["Friedel-Crafts acylation", "FC acylation"],
+    category="C-C Bond Formation", type_="Electrophilic Aromatic Substitution",
+    summary="Lewis acid-mediated acylation of aromatic rings with acyl halides or anhydrides. No rearrangement or over-acylation.",
+    conditions="ArH + RCOCl + AlCl3 (>1 equiv), CH2Cl2, 0°C to RT. AlCl3 is consumed (stoichiometric — complexes with ketone product).",
+    substrate="Electron-rich arenes + acyl chlorides/anhydrides → aryl ketones.",
+    limitations="Requires >1 equiv AlCl3 (product-Lewis acid complex). Deactivated arenes unreactive. Works for ketone synthesis where alkylation fails (no rearrangement, no polyacylation).",
+    mechanism="AlCl3 + RCOCl → acylium ion (or complex) → EAS → arenium ion → deprotonation.",
+    refs="Friedel, Crafts, J. Chem. Soc. 1877, 32, 725.",
+    related="Friedel-Crafts alkylation, Fries rearrangement, Haworth synthesis",
+    functional_groups="arene, acyl halide")
+
+_nr("Wittig Rearrangement",
+    aliases=["[1,2]-Wittig", "[2,3]-Wittig"],
+    category="Rearrangement", type_="[1,2] or [2,3]-Sigmatropic",
+    summary="Base-induced rearrangement of ethers. [1,2]-Wittig: α-alkoxy carbanion → 1,2-shift → alkoxide. [2,3]-Wittig: α-allyloxy carbanion → [2,3]-sigmatropic → homoallylic alkoxide.",
+    conditions="nBuLi or LDA, THF, -78°C. Substrate must have acidic proton α to oxygen.",
+    substrate="[1,2]: R-O-CHR' (with stabilizing group) → alcohol. [2,3]: allyl ethers with α-proton → homoallylic alcohols.",
+    limitations="Requires α-proton on ether. [1,2] is stepwise (radical pair). [2,3] is concerted and stereospecific.",
+    mechanism="[1,2]: homolytic C-O cleavage → radical pair → recombination. [2,3]: concerted suprafacial [2,3]-sigmatropic shift.",
+    refs="Wittig, Löhmann, Justus Liebigs Ann. Chem. 1942, 550, 260. Nakai, Mikami, Chem. Rev. 1986, 86, 885.",
+    related="Claisen rearrangement, Stevens rearrangement",
+    functional_groups="ether, allyl ether")
+
+_nr("Swern Oxidation",
+    aliases=["Swern"],
+    category="Oxidation", type_="Alcohol → Aldehyde/Ketone",
+    summary="Oxidation of primary/secondary alcohols to aldehydes/ketones using DMSO/oxalyl chloride.",
+    conditions="(COCl)2 + DMSO in CH2Cl2 at -78°C, then add alcohol, then Et3N. Warm to RT.",
+    substrate="Primary → aldehyde. Secondary → ketone.",
+    limitations="Must maintain -78°C. Generates Me2S (smell).",
+    mechanism="DMSO activated by oxalyl chloride → alkoxysulfonium → elimination.",
+    refs="Omura, Swern, Tetrahedron 1978, 34, 1651.",
+    related="Dess-Martin, PCC, TEMPO, Parikh-Doering",
+    functional_groups="alcohol")
+
+_nr("Oppenauer Oxidation",
+    aliases=["Oppenauer"],
+    category="Oxidation", type_="Alcohol → Ketone (Al-mediated)",
+    summary="Aluminum alkoxide-catalyzed oxidation of secondary alcohols to ketones using acetone as hydride acceptor. Reverse of MPV reduction.",
+    conditions="Al(OiPr)3, excess acetone, reflux.",
+    substrate="Secondary alcohols → ketones. Mild — tolerates alkenes, alkynes.",
+    limitations="Equilibrium reaction. Excess acetone needed. Not practical for primary alcohols.",
+    mechanism="Meerwein-Ponndorf-Verley in reverse: Al coordinates both substrate and acetone → hydride transfer → ketone + isopropanol.",
+    refs="Oppenauer, Recl. Trav. Chim. Pays-Bas 1937, 56, 137.",
+    related="MPV reduction, Ley (TPAP), Swern",
+    functional_groups="secondary alcohol")
+
+_nr("Meerwein-Ponndorf-Verley Reduction",
+    aliases=["MPV", "Meerwein-Ponndorf-Verley", "MPV reduction"],
+    category="Reduction", type_="Ketone → Alcohol (Al-mediated)",
+    summary="Aluminum alkoxide-catalyzed transfer hydrogenation of ketones using isopropanol as hydride source.",
+    conditions="Al(OiPr)3, excess iPrOH, reflux.",
+    substrate="Ketones → secondary alcohols. Highly chemoselective for C=O over C=C.",
+    limitations="Equilibrium. Does not reduce esters, amides, etc.",
+    mechanism="Six-membered cyclic TS: Al coordinates ketone substrate and iPrOH → hydride transfer → alcohol + acetone.",
+    refs="Meerwein, Schmidt, Justus Liebigs Ann. Chem. 1925, 444, 221.",
+    related="Oppenauer oxidation, Noyori transfer hydrogenation",
+    functional_groups="ketone")
+
+_nr("Barton Decarboxylation",
+    aliases=["Barton", "Barton radical decarboxylation"],
+    category="Radical", type_="Decarboxylation",
+    summary="Radical decarboxylation of carboxylic acids via Barton esters (thiohydroxamate esters). Very general radical generation method.",
+    conditions="RCOOH → mixed anhydride with Barton's reagent (N-hydroxy-2-thiopyridone sodium salt) → photolysis or AIBN → radical R· + CO2. Trap with Bu3SnH or other radical trap.",
+    substrate="Carboxylic acids → R· radical → R-H, R-Br, R-SPy, etc. Works with 1°, 2°, 3° acids.",
+    limitations="Requires Barton ester preparation. Radical conditions (sensitivity to O2). Tin reagents toxic.",
+    mechanism="Barton ester → photolysis → carboxyl radical → β-scission (loss of CO2) → carbon radical → trapping.",
+    refs="Barton, Crich, Motherwell, J. Chem. Soc. Chem. Commun. 1983, 939.",
+    related="Hunsdiecker, Kolbe electrolysis",
+    functional_groups="carboxylic acid")
+
+_nr("Fischer Indole Synthesis",
+    aliases=["Fischer indole"],
+    category="Heterocycle Formation", type_="Indole Synthesis",
+    summary="Synthesis of indoles from aryl hydrazones via [3,3]-sigmatropic rearrangement and loss of NH3.",
+    conditions="Aryl hydrazone + Lewis or Brønsted acid (ZnCl2, HCl, AcOH, polyphosphoric acid), heat (100-200°C).",
+    substrate="Aryl hydrazine + aldehyde/ketone → hydrazone → indole. Regiochemistry predictable for unsymmetrical ketones.",
+    limitations="High temperatures. Regiochemistry issues with unsymmetrical ketones (migrate more substituted carbon). NH3 loss.",
+    mechanism="Tautomerization to ene-hydrazine → [3,3]-sigmatropic rearrangement → re-aromatization → loss of NH3 → indole.",
+    refs="Fischer, Jourdan, Ber. Dtsch. Chem. Ges. 1883, 16, 2241.",
+    related="Bartoli, Leimgruber-Batcho, Madelung indole synthesis",
+    functional_groups="aryl hydrazine, aldehyde, ketone, indole")
+
+_nr("Paal-Knorr Synthesis",
+    aliases=["Paal-Knorr furan", "Paal-Knorr pyrrole", "Paal-Knorr"],
+    category="Heterocycle Formation", type_="Furan/Pyrrole/Thiophene Synthesis",
+    summary="Synthesis of furans, pyrroles, or thiophenes from 1,4-dicarbonyls. Choice of reagent determines product.",
+    conditions="1,4-Diketone + acid catalyst → furan. + Primary amine → pyrrole. + Lawesson's reagent or P4S10 → thiophene.",
+    substrate="1,4-Dicarbonyl compounds → 5-membered heterocycles.",
+    limitations="Requires accessible 1,4-dicarbonyl (can be synthesized via Stetter, 1,4-addition, etc.).",
+    mechanism="Double condensation/cyclodehydration. Furan: acid-catalyzed enolization → ring closure → dehydration × 2.",
+    refs="Paal, Ber. Dtsch. Chem. Ges. 1884, 17, 2756. Knorr, Ber. Dtsch. Chem. Ges. 1884, 17, 1635.",
+    related="Hantzsch pyrrole, Feist-Bénary furan",
+    functional_groups="1,4-diketone, furan, pyrrole, thiophene")
+
+# --- Additional Cross-Coupling ---
+
+_nr("Buchwald-Hartwig Amination (C-O)",
+    aliases=["Buchwald etherification", "C-O coupling"],
+    category="C-C Bond Formation", type_="Cross-Coupling",
+    summary="Pd-catalyzed C-O bond formation between aryl halides and alcohols/phenols.",
+    conditions="Pd2(dba)3 or Pd(OAc)2, bulky phosphine (RuPhos, tBuXPhos), Cs2CO3 or NaOtBu, toluene, 80-110°C.",
+    substrate="Aryl halides + phenols, primary/secondary alcohols.",
+    limitations="Less developed than C-N variant. Competing β-hydride elimination with 2° alcohols.",
+    mechanism="Oxidative addition → coordination/deprotonation of alcohol → reductive elimination.",
+    refs="Vorogushin, Huang, Buchwald, JACS 2005, 127, 8146.",
+    related="Buchwald-Hartwig, Ullmann, Chan-Lam",
+    functional_groups="aryl halide, alcohol, ether")
+
+_nr("Chan-Lam Coupling",
+    aliases=["Chan-Lam-Evans", "copper-mediated coupling"],
+    category="C-C Bond Formation", type_="Cross-Coupling",
+    summary="Cu-mediated coupling of boronic acids with amines, phenols, or thiols under mild conditions.",
+    conditions="Cu(OAc)2 (stoich. or cat.), Et3N or pyridine, CH2Cl2 or DMF, RT, air atmosphere. No Pd required.",
+    substrate="ArB(OH)2 + amines, phenols, amides, or alcohols. Open-flask conditions (O2 as terminal oxidant).",
+    limitations="Often requires stoichiometric Cu. Homo-coupling side reaction. Less reliable than Pd-catalyzed methods.",
+    mechanism="Transmetalation → Cu(II)/Cu(III) oxidation → reductive elimination. Cu(I)/Cu(II)/Cu(III) cycle.",
+    refs="Chan, Lam, JACS 1998, 120, 8657. Evans, Katz, West, Tetrahedron Lett. 1998, 39, 2937.",
+    related="Buchwald-Hartwig, Ullmann, Suzuki",
+    functional_groups="boronic acid, amine, phenol")
+
+_nr("Ullmann Coupling",
+    aliases=["Ullmann reaction", "Ullmann-Goldberg"],
+    category="C-C Bond Formation", type_="Cross-Coupling",
+    summary="Cu-catalyzed coupling of aryl halides with amines, phenols, or thiols. Modern variants use mild conditions.",
+    conditions="CuI (5-20 mol%), diamine ligand (DMEDA, proline), K2CO3 or Cs2CO3, DMSO or dioxane, 80-110°C.",
+    substrate="Aryl iodides/bromides + amines, phenols, amides, thiols. Original: 2 ArX → Ar-Ar (high T, Cu powder).",
+    limitations="Less reliable than Pd catalysis. Requires iodides typically. High temperatures.",
+    mechanism="Cu(I)/Cu(III) oxidative addition/reductive elimination cycle (debated: SET vs concerted).",
+    refs="Ullmann, Ber. 1903, 36, 2382. Ma, Cai, Acc. Chem. Res. 2008, 41, 1450.",
+    related="Buchwald-Hartwig, Chan-Lam",
+    functional_groups="aryl halide, amine, phenol")
+
+_nr("Tsuji-Trost Reaction",
+    aliases=["Trost allylation", "Pd-allyl", "allylic substitution"],
+    category="C-C Bond Formation", type_="Substitution",
+    summary="Pd-catalyzed allylic substitution. Nucleophilic attack on π-allyl Pd complex.",
+    conditions="Pd(PPh3)4 or [Pd(allyl)Cl]2, ligand (PPh3, DPPF, or chiral PHOX for asymmetric), THF or CH2Cl2, RT-60°C.",
+    substrate="Allylic acetates, carbonates, halides + soft nucleophiles (malonates, amines) or hard nucleophiles (organozinc).",
+    limitations="Regioselectivity depends on nucleophile hardness (soft → less substituted, hard → more substituted). Linear/branched selectivity.",
+    mechanism="Oxidative addition → π-allyl complex formation → nucleophilic attack (outer sphere for soft, inner sphere for hard nuc).",
+    refs="Trost, Fullerton, JACS 1973, 95, 292. Trost, Van Vranken, Chem. Rev. 1996, 96, 395.",
+    related="Heck, Suzuki",
+    functional_groups="allylic acetate, malonate, amine")
+
+_nr("Hiyama Coupling",
+    aliases=["Hiyama cross-coupling", "Hiyama-Denmark"],
+    category="C-C Bond Formation", type_="Cross-Coupling",
+    summary="Pd-catalyzed coupling of organosilanes with organic halides. Requires fluoride activation.",
+    conditions="Pd(0) cat., TBAF or CsF (activator), THF or DMF, 50-100°C.",
+    substrate="RSiR'3 (trialkoxysilanes, silanols) + ArX. Organosilanes are cheap, stable, low toxicity.",
+    limitations="Requires activator (F⁻ or base) for transmetalation. Lower reactivity than boronic acids.",
+    mechanism="Oxidative addition → F⁻-activated transmetalation (pentacoordinate Si) → reductive elimination.",
+    refs="Hiyama, Hatanaka, Pure Appl. Chem. 1994, 66, 1471. Denmark, Regens, Acc. Chem. Res. 2008, 41, 1486.",
+    related="Suzuki, Stille, Negishi",
+    functional_groups="organosilane, aryl halide")
+
+_nr("Liebeskind-Srogl Coupling",
+    aliases=["thioester coupling"],
+    category="C-C Bond Formation", type_="Cross-Coupling",
+    summary="Pd-catalyzed coupling of thioester C-S bond with boronic acids under neutral conditions (no base needed).",
+    conditions="Pd(PPh3)4, CuTC (Cu(I) thienylcarboxylate), THF, RT-50°C. pH-neutral.",
+    substrate="Thioester + ArB(OH)2. Produces ketone. Also works with thioethers.",
+    limitations="Requires stoichiometric Cu co-catalyst. Thioester substrate preparation.",
+    mechanism="Oxidative addition of C-S bond → Cu-assisted transmetalation → reductive elimination.",
+    refs="Liebeskind, Srogl, JACS 2000, 122, 11260.",
+    related="Suzuki, Stille, Fukuyama coupling",
+    functional_groups="thioester, boronic acid, ketone")
+
+_nr("Fukuyama Coupling",
+    aliases=["Fukuyama reduction"],
+    category="C-C Bond Formation", type_="Cross-Coupling",
+    summary="Pd-catalyzed coupling of thioesters with organozinc reagents to form ketones. Selective mono-addition.",
+    conditions="Pd(PPh3)4, organozinc (RZnX), THF, 0°C to RT.",
+    substrate="Thioesters + RZnX → ketones. Does NOT over-add to give alcohol (unlike aldehydes + RZnX).",
+    limitations="Requires preparation of organozinc reagent. Thioester substrate required.",
+    mechanism="Oxidative addition of C-S bond → transmetalation with RZnX → reductive elimination.",
+    refs="Tokuyama, Yokoshima, Mori, Li, Fukuyama, JACS 1998, 120, 11235.",
+    related="Negishi, Weinreb amide, Liebeskind-Srogl",
+    functional_groups="thioester, organozinc, ketone")
+
+# --- Olefination Reactions ---
+
+_nr("Still-Gennari Olefination",
+    aliases=["Still-Gennari"],
+    category="C-C Bond Formation", type_="Olefination",
+    summary="Modified HWE reaction that gives Z-alkenes selectively using bis(trifluoroethyl) phosphonate.",
+    conditions="(CF3CH2O)2P(O)CH2CO2R, KHMDS, 18-crown-6, THF, -78°C.",
+    substrate="Aldehydes → Z-α,β-unsaturated esters (>95:5 Z:E).",
+    limitations="Expensive reagent. Requires low temperature and crown ether. Limited to ester-stabilized ylides.",
+    mechanism="Modified HWE. Kinetic control at low T. cis-Oxaphosphetane forms preferentially due to CF3 groups.",
+    refs="Still, Gennari, Tetrahedron Lett. 1983, 24, 4405.",
+    related="HWE, Wittig, Julia, Ando",
+    functional_groups="aldehyde, phosphonate, Z-alkene")
+
+_nr("Takai Olefination",
+    aliases=["Takai reaction", "Takai-Utimoto"],
+    category="C-C Bond Formation", type_="Olefination",
+    summary="CrCl2-mediated conversion of aldehydes to E-vinyl halides using CHX3.",
+    conditions="CrCl2 (6 equiv), CHI3 or CHBr3, THF, 0°C to RT. cat. NiCl2 sometimes added.",
+    substrate="RCHO → RCH=CHX (X = I or Br). Highly E-selective.",
+    limitations="Stoichiometric Cr (toxic, but Cr(II) less so). Over-reduction possible.",
+    mechanism="Cr(II) reduces CHX3 to Cr-carbenoid → Wittig-like addition to aldehyde.",
+    refs="Takai, Nitta, Utimoto, JACS 1986, 108, 7408.",
+    related="Wittig, HWE, Nozaki-Hiyama-Kishi",
+    functional_groups="aldehyde, vinyl halide")
+
+_nr("Tebbe Olefination",
+    aliases=["Tebbe reagent", "Petasis olefination"],
+    category="C-C Bond Formation", type_="Olefination",
+    summary="Ti-mediated methylenation of carbonyls (including esters, amides) to terminal alkenes using Tebbe or Petasis reagent.",
+    conditions="Tebbe reagent (Cp2TiCl2/AlMe3 complex) or Petasis reagent (Cp2TiMe2), THF, -40°C to RT, pyridine base.",
+    substrate="Ketones, esters, lactones, amides → methylene (C=CH2). Works on carbonyls that Wittig cannot.",
+    limitations="Only methylenation (no other alkylidenes with Tebbe). Sensitive reagent. Stoichiometric Ti.",
+    mechanism="α-Elimination → Cp2Ti=CH2 (titanium carbene) → [2+2] cycloaddition with C=O → retro-[2+2] fragmentation.",
+    refs="Tebbe, Parshall, Reddy, JACS 1978, 100, 3611. Petasis, Bzowej, JACS 1990, 112, 6392.",
+    related="Wittig, Lombardo, Nysted",
+    functional_groups="ketone, ester, alkene")
+
+# --- Oxidation Reactions ---
+
+_nr("Corey-Kim Oxidation",
+    aliases=["Corey-Kim"],
+    category="Oxidation", type_="Alcohol Oxidation",
+    summary="Oxidation of alcohols using NCS/DMS, followed by Et3N. Mild alternative to Swern.",
+    conditions="NCS, DMS, CH2Cl2, -25°C → add alcohol → Et3N, warm to RT.",
+    substrate="1° alcohols → aldehydes. 2° alcohols → ketones.",
+    limitations="Similar to Swern. DMS byproduct (odor). NCS must be fresh.",
+    mechanism="NCS activates DMS → sulfonium salt → alkoxysulfonium ylide → intramolecular elimination.",
+    refs="Corey, Kim, JACS 1972, 94, 7586.",
+    related="Swern, Pfitzner-Moffatt, Parikh-Doering",
+    functional_groups="alcohol, aldehyde, ketone")
+
+_nr("Parikh-Doering Oxidation",
+    aliases=["Doering oxidation", "SO3-pyridine oxidation"],
+    category="Oxidation", type_="Alcohol Oxidation",
+    summary="Mild DMSO-based oxidation using SO3·pyridine complex. Room temperature, no cryogenic conditions needed.",
+    conditions="SO3·py, DMSO, Et3N, CH2Cl2, 0°C to RT.",
+    substrate="1° → aldehyde, 2° → ketone. Very mild conditions.",
+    limitations="DMSO required (difficult to remove). Slower than Swern.",
+    mechanism="SO3·py activates DMSO → alkoxysulfonium intermediate → Kornblum elimination via Et3N.",
+    refs="Parikh, Doering, JACS 1967, 89, 5505.",
+    related="Swern, Corey-Kim, Pfitzner-Moffatt",
+    functional_groups="alcohol, aldehyde, ketone")
+
+_nr("IBX Oxidation",
+    aliases=["IBX", "2-iodoxybenzoic acid oxidation"],
+    category="Oxidation", type_="Alcohol Oxidation",
+    summary="Mild, selective alcohol oxidation using IBX (2-iodoxybenzoic acid). Works in DMSO.",
+    conditions="IBX (1.1-2 equiv), DMSO, RT, 1-12h. Filtered to remove iodosobenzoic acid byproduct.",
+    substrate="1° → aldehyde (no over-oxidation!), 2° → ketone. Tolerates many functional groups.",
+    limitations="IBX insoluble in most solvents except DMSO. Explosive when heated dry. Use freshly prepared.",
+    mechanism="Hypervalent iodine(V). Ligand exchange at I(V) → [2,3]-sigmatropic rearrangement → elimination.",
+    refs="Frigerio, Santagostino, J. Org. Chem. 1999, 64, 4537.",
+    related="Dess-Martin, Swern, TEMPO",
+    functional_groups="alcohol, aldehyde, ketone")
+
+_nr("Rubottom Oxidation",
+    aliases=["Rubottom"],
+    category="Oxidation", type_="α-Hydroxylation",
+    summary="α-Hydroxylation of enol silyl ethers using mCPBA to give α-hydroxy ketones.",
+    conditions="Silyl enol ether + mCPBA, CH2Cl2, 0°C to RT → α-silyloxy ketone. Then TBAF or acid for deprotection.",
+    substrate="Silyl enol ethers → α-hydroxy ketones. Regiospecific (defined by enolization).",
+    limitations="Requires preparation of silyl enol ether (regiochemistry must be set). Over-oxidation possible.",
+    mechanism="Electrophilic epoxidation of silyl enol ether → epoxide → 1,4-O→O silyl migration → α-silyloxyketone.",
+    refs="Rubottom, Vazquez, Pelegrina, Tetrahedron Lett. 1974, 15, 4319.",
+    related="Davis oxaziridine, Sharpless AD",
+    functional_groups="silyl enol ether, α-hydroxy ketone")
+
+_nr("Lemieux-Johnson Oxidation",
+    aliases=["Lemieux-Johnson", "OsO4-NaIO4 cleavage"],
+    category="Oxidation", type_="Alkene Cleavage",
+    summary="One-step oxidative cleavage of alkenes to carbonyl compounds using OsO4/NaIO4.",
+    conditions="cat. OsO4 (1-5 mol%), NaIO4 (2-3 equiv), dioxane/H2O or THF/H2O, RT.",
+    substrate="Alkenes → 2 carbonyl fragments (aldehydes and/or ketones). Cleaves C=C completely.",
+    limitations="Stoichiometric NaIO4 needed. Over-oxidation of aldehydes possible. OsO4 is toxic and expensive.",
+    mechanism="OsO4 dihydroxylation → diol → NaIO4 cleaves diol → 2 carbonyls + regenerates OsO4.",
+    refs="Lemieux, Johnson, J. Org. Chem. 1956, 21, 478.",
+    related="Ozonolysis, Sharpless dihydroxylation",
+    functional_groups="alkene, aldehyde, ketone")
+
+_nr("Shi Epoxidation",
+    aliases=["Shi asymmetric epoxidation"],
+    category="Oxidation", type_="Asymmetric Epoxidation",
+    summary="Organocatalytic asymmetric epoxidation of trans-disubstituted and trisubstituted alkenes using fructose-derived ketone.",
+    conditions="Shi catalyst (30 mol%), Oxone, K2CO3, Na2B4O7 buffer, CH3CN/H2O, 0°C.",
+    substrate="trans-Disubstituted, trisubstituted alkenes. ee >90% typically.",
+    limitations="Less effective for cis- and terminal alkenes. High catalyst loading. pH-sensitive.",
+    mechanism="Ketone + Oxone → dioxirane (chiral) → concerted O-transfer to alkene.",
+    refs="Tu, Wang, Frohn, He, Yu, Tang, Shi, JACS 2003, 125, 14354.",
+    related="Sharpless epoxidation, Jacobsen epoxidation, mCPBA",
+    functional_groups="alkene, epoxide")
+
+_nr("Jacobsen Epoxidation",
+    aliases=["Jacobsen-Katsuki"],
+    category="Oxidation", type_="Asymmetric Epoxidation",
+    summary="Mn(III)-salen-catalyzed asymmetric epoxidation of unfunctionalized cis-disubstituted alkenes.",
+    conditions="Mn(salen) cat. (1-5 mol%), NaOCl or mCPBA (oxidant), CH2Cl2, 0°C to RT.",
+    substrate="cis-Disubstituted and trisubstituted alkenes (complementary to Sharpless AE which requires allylic alcohol).",
+    limitations="trans-Alkenes give lower ee. Terminal alkenes variable. Catalyst decomposition over time.",
+    mechanism="Mn(III) → Mn(V)=O (via oxidant) → concerted (though stepwise debated) O-transfer to alkene. Salen controls facial selectivity.",
+    refs="Zhang, Loebach, Wilson, Jacobsen, JACS 1990, 112, 2801.",
+    related="Sharpless epoxidation, Shi epoxidation, mCPBA",
+    functional_groups="alkene, epoxide")
+
+_nr("Upjohn Dihydroxylation",
+    aliases=["OsO4 dihydroxylation", "osmylation"],
+    category="Oxidation", type_="Dihydroxylation",
+    summary="Catalytic OsO4-mediated syn-dihydroxylation of alkenes using NMO as co-oxidant.",
+    conditions="cat. OsO4 (1-5 mol%), NMO (1.5 equiv), acetone/H2O or tBuOH/H2O, RT.",
+    substrate="Any alkene → syn-1,2-diol. Electron-rich alkenes react faster. Stereospecific syn addition.",
+    limitations="OsO4 is toxic and volatile. Can over-oxidize to cleave diol if NaIO4 is present.",
+    mechanism="[3+2] cycloaddition of OsO4 across alkene → osmate(VI) ester → hydrolysis → diol + Os(VI). NMO reoxidizes Os(VI) to OsO4.",
+    refs="Van Rheenen, Kelly, Cha, Tetrahedron Lett. 1976, 17, 1973.",
+    related="Sharpless AD, Lemieux-Johnson",
+    functional_groups="alkene, diol")
+
+_nr("Wohl-Ziegler Bromination",
+    aliases=["NBS bromination", "allylic bromination"],
+    category="Oxidation", type_="Halogenation",
+    summary="Allylic or benzylic bromination using NBS (N-bromosuccinimide) via radical mechanism.",
+    conditions="NBS (1 equiv), radical initiator (AIBN, BPO, or light), CCl4 or CH2Cl2, reflux or hν.",
+    substrate="Allylic, benzylic C-H → C-Br. Maintains alkene geometry. Regioselective for weakest C-H.",
+    limitations="Mixture of products if multiple allylic positions. Competing addition to alkene if [Br2] too high. Over-bromination.",
+    mechanism="Radical chain: initiation → Br• abstracts allylic/benzylic H → C• + NBS → C-Br + succinimidyl radical → propagation.",
+    refs="Wohl, Ber. 1919, 52, 51. Ziegler, Angew. Chem. 1942, 55, 339.",
+    related="radical bromination, Appel",
+    functional_groups="allylic C-H, benzylic C-H, bromide")
+
+# --- Reduction Reactions ---
+
+_nr("Staudinger Ligation",
+    aliases=["Staudinger reaction (amine)"],
+    category="Reduction", type_="Azide Reduction",
+    summary="Reduction of organic azides to amines using PPh3, via an iminophosphorane intermediate.",
+    conditions="PPh3, THF/H2O, RT. Hydrolyze the iminophosphorane with water.",
+    substrate="RN3 → RNH2. Very selective, tolerates many functional groups.",
+    limitations="Produces Ph3P=O (stoichiometric, difficult to remove). The Bertozzi variant traps the intermediate for bioconjugation.",
+    mechanism="PPh3 attacks azide → phosphazide → loss of N2 → iminophosphorane (R-N=PPh3) → hydrolysis → RNH2 + O=PPh3.",
+    refs="Staudinger, Meyer, Helv. Chim. Acta 1919, 2, 635.",
+    related="Curtius, Gabriel synthesis, hydrogenation",
+    functional_groups="azide, amine, phosphine")
+
+_nr("Noyori Asymmetric Hydrogenation",
+    aliases=["BINAP hydrogenation", "Noyori hydrogenation"],
+    category="Reduction", type_="Asymmetric Hydrogenation",
+    summary="Ru-BINAP-catalyzed asymmetric hydrogenation of functionalized alkenes and ketones.",
+    conditions="Ru(OAc)2(BINAP) or RuCl2(BINAP), H2 (50-100 atm), MeOH or iPrOH, 25-50°C.",
+    substrate="β-Keto esters → β-hydroxy esters. Functionalized alkenes (enamides, allylic alcohols). ee >95% typical.",
+    limitations="Requires coordinating group near C=C or C=O for high ee. High H2 pressure. Expensive catalyst.",
+    mechanism="Substrate coordinates via functional group → H2 oxidative addition → migratory insertion (enantioselective face).",
+    refs="Noyori, Ohkuma, Kitamura, JACS 1987, 109, 5856. Nobel Prize 2001.",
+    related="CBS reduction, Corey-Bakshi-Shibata, Rh-DuPhos",
+    functional_groups="ketone, alkene, β-hydroxy ester")
+
+_nr("Bouveault-Blanc Reduction",
+    aliases=["Bouveault-Blanc", "Na/alcohol reduction"],
+    category="Reduction", type_="Ester Reduction",
+    summary="Classical reduction of esters to alcohols using Na metal in an alcohol solvent (replaced by LiAlH4 in modern chemistry).",
+    conditions="Na metal, EtOH or nBuOH, reflux. Historical method.",
+    substrate="Esters → primary alcohols + alcohol from ester alkyl group.",
+    limitations="Dangerous (Na + protic solvent). Superseded by LiAlH4 and DIBAL-H.",
+    mechanism="Single-electron transfer from Na → radical anion → further reduction → alkoxide → protonation.",
+    refs="Bouveault, Blanc, Compt. Rend. 1903, 136, 1676.",
+    related="LiAlH4, DIBAL-H, Birch reduction",
+    functional_groups="ester, alcohol")
+
+_nr("Midland Reduction",
+    aliases=["Alpine-Borane", "Midland alpine borane"],
+    category="Reduction", type_="Asymmetric Reduction",
+    summary="Asymmetric reduction of prochiral ketones using B-3-pinanyl-9-BBN (Alpine-Borane).",
+    conditions="Alpine-Borane (from 9-BBN + α-pinene), THF, 0°C to RT. Slow, but high ee for propargylic ketones.",
+    substrate="α,β-Ynones, α-halo ketones → chiral propargylic/secondary alcohols. Best for substrates with small/large differentiation.",
+    limitations="Slow reaction. Limited substrate scope (best for acetylenic ketones). Requires large excess sometimes.",
+    mechanism="Intramolecular hydride delivery via 6-membered TS. Boat-like transition state determines enantioselectivity.",
+    refs="Midland, Greer, Tramontano, Zderic, JACS 1979, 101, 2352.",
+    related="CBS reduction, Noyori, DIP-Cl",
+    functional_groups="ketone, propargylic alcohol")
+
+_nr("Meerwein Reduction",
+    aliases=["Meerwein-Ponndorf-Verley", "MPV reduction"],
+    category="Reduction", type_="Carbonyl Reduction",
+    summary="Al(OiPr)3-catalyzed transfer hydrogenation of ketones/aldehydes using iPrOH as hydride source.",
+    conditions="Al(OiPr)3, iPrOH, reflux. Also: Ln(OiPr)3, Sm(OiPr)3, or Ru catalysts for modern variants.",
+    substrate="Ketones → 2° alcohols, aldehydes → 1° alcohols. Chemoselective: does not reduce esters, alkenes, etc.",
+    limitations="Equilibrium reaction (remove acetone to drive forward). Slow with Al(OiPr)3.",
+    mechanism="6-membered cyclic TS: Al coordinates both substrate C=O and iPrO-H → hydride transfer via Zimmerman-Traxler-like TS.",
+    refs="Meerwein, Schmidt, Annalen 1925, 444, 221.",
+    related="Oppenauer (reverse), NaBH4, CBS",
+    functional_groups="ketone, aldehyde, alcohol")
+
+# ---- v7.0 additions: 65+ new reactions ----
+
+_nr("Bamford-Stevens Reaction",
+    aliases=["Bamford-Stevens", "Shapiro Reaction"],
+    category="C-C Bond Formation", type_="Elimination",
+    summary="Tosylhydrazones → alkenes via diazo intermediates under basic conditions.",
+    conditions="Tosylhydrazone + NaOMe or NaH, heat (150–200 °C) or nBuLi (Shapiro variant, milder). Shapiro: 2 eq nBuLi, –78 °C → rt.",
+    substrate="Ketone-derived tosylhydrazones → alkenes. Shapiro gives less-substituted alkene (kinetic).",
+    limitations="Bamford-Stevens: carbene rearrangements at high T. Shapiro requires strong base.",
+    mechanism="Base removes NH → diazo intermediate → loss of N₂ → carbene (protic) or vinyl anion (Shapiro: base abstracts second H).",
+    refs="Bamford, Stevens, J. Chem. Soc. 1952, 4735. Shapiro, Heath, JACS 1967, 89, 5734.",
+    related="Wolff-Kishner, Julia Olefination",
+    functional_groups="ketone, alkene, tosylhydrazone")
+
+_nr("Bischler-Napieralski Reaction",
+    aliases=["Bischler-Napieralski"],
+    category="Heterocycle Formation", type_="Ring Closure",
+    summary="Cyclodehydration of β-arylethylamides to 3,4-dihydroisoquinolines.",
+    conditions="POCl3 or P2O5, reflux in toluene/xylene. Modern: Tf2O, 2-fluoropyridine.",
+    substrate="β-Arylethylamides → dihydroisoquinolines. Electron-rich arenes cyclize faster.",
+    limitations="Electron-poor arenes fail. Requires acyl group on nitrogen.",
+    mechanism="POCl3 activates carbonyl → electrophilic cyclization → dehydration → imine.",
+    refs="Bischler, Napieralski, Ber. 1893, 26, 1903.",
+    related="Pictet-Spengler, Pomeranz-Fritsch",
+    functional_groups="amide, isoquinoline")
+
+_nr("Buchner Ring Expansion",
+    aliases=["Buchner reaction"],
+    category="Rearrangement", type_="Ring Expansion",
+    summary="Carbene insertion into benzene ring → cycloheptatriene (tropylium precursor).",
+    conditions="α-Diazo esters + Rh2(OAc)4, or Cu catalysis. Also photolytic.",
+    substrate="Benzene, substituted arenes → cycloheptatrienes/norcaradienes.",
+    limitations="Mixtures of isomers. Competing C-H insertion.",
+    mechanism="Rh-carbenoid cyclopropanates benzene → norcaradiene ↔ cycloheptatriene electrocyclic equilibrium.",
+    refs="Buchner, Curtius, Ber. 1885, 18, 2377.",
+    related="Diels-Alder, Claisen Rearrangement",
+    functional_groups="arene, carbene, cycloheptatriene")
+
+_nr("Cannizzaro Reaction",
+    aliases=["Cannizzaro"],
+    category="Oxidation", type_="Disproportionation",
+    summary="Base-mediated disproportionation of non-enolizable aldehydes → alcohol + carboxylate.",
+    conditions="Conc. NaOH or KOH (50%), rt or mild heat. Crossed Cannizzaro: HCHO as reductant.",
+    substrate="Aldehydes without α-H (ArCHO, R3CCHO, HCHO). Crossed variant uses formaldehyde.",
+    limitations="Only non-enolizable aldehydes. 50% max yield per product (disproportionation).",
+    mechanism="OH⁻ adds to C=O → tetrahedral alkoxide → hydride transfer to second aldehyde → alcohol + carboxylate.",
+    refs="Cannizzaro, Liebigs Ann. 1853, 88, 129.",
+    related="Tischenko, Aldol",
+    functional_groups="aldehyde, carboxylic acid, alcohol")
+
+_nr("Chichibabin Amination",
+    aliases=["Chichibabin reaction"],
+    category="C-N Bond Formation", type_="Nucleophilic Aromatic Substitution",
+    summary="Direct amination of pyridines and related heterocycles with NaNH2.",
+    conditions="NaNH2, toluene or mineral oil, 100–110 °C. Also: LiNH2, KNH2.",
+    substrate="Pyridine → 2-aminopyridine. Also quinoline, isoquinoline, pyrimidine.",
+    limitations="Strong base required. May give mixtures with polysubstituted substrates.",
+    mechanism="NaNH2 attacks C-2 of pyridine → addition → NaH eliminated → 2-aminopyridine.",
+    refs="Chichibabin, Zeide, JRCS 1914, 46, 1216.",
+    related="Buchwald-Hartwig, Gabriel",
+    functional_groups="pyridine, amine")
+
+_nr("Claisen Condensation",
+    aliases=["Claisen condensation"],
+    category="C-C Bond Formation", type_="Condensation",
+    summary="Base-mediated self-condensation of esters to give β-keto esters.",
+    conditions="NaOEt/EtOH or LDA/THF, –78 °C → rt. Crossed: use LDA for controlled selectivity.",
+    substrate="Esters with α-H → β-keto esters. Dieckmann: intramolecular (5- or 6-membered rings).",
+    limitations="Requires α-H. Self-condensation gives mixtures with crossed variants.",
+    mechanism="Base deprotonates α-H → enolate attacks ester C=O → tetrahedral intermediate → alkoxide leaves → β-keto ester.",
+    refs="Claisen, Ber. 1887, 20, 655.",
+    related="Aldol, Knoevenagel, Dieckmann",
+    functional_groups="ester, β-keto ester")
+
+_nr("Comins' Reagent",
+    aliases=["Comins reagent", "vinyl triflate formation"],
+    category="Functional Group Interconversion", type_="Triflation",
+    summary="N-(5-Chloro-2-pyridyl)triflimide converts enolates to vinyl triflates.",
+    conditions="LDA, THF, –78 °C → add Comins' reagent → vinyl triflate.",
+    substrate="Ketone enolates → vinyl triflates. Regiochemistry set by enolization conditions.",
+    limitations="Kinetic vs thermodynamic enolate control critical. Triflimide byproduct can complicate purification.",
+    mechanism="Enolate O attacks electrophilic S of Tf₂NR → Tf transferred to O → vinyl triflate.",
+    refs="Comins, Dehghani, Tetrahedron Lett. 1992, 33, 6299.",
+    related="Tf₂O, Heck, Suzuki, Sonogashira",
+    functional_groups="ketone, vinyl triflate, enolate")
+
+_nr("Cope Elimination",
+    aliases=["Cope elimination"],
+    category="Functional Group Interconversion", type_="Elimination",
+    summary="Thermal syn-elimination of amine oxides to give alkenes + hydroxylamine.",
+    conditions="mCPBA oxidation of amine → amine oxide, then heat (100–150 °C).",
+    substrate="Tertiary amines → alkenes. Gives Hofmann (less substituted) product.",
+    limitations="High temperature. Requires β-H syn to N-oxide. Hofmann selectivity.",
+    mechanism="Concerted syn-periplanar [1,5]-sigmatropic: 5-membered cyclic TS → alkene + R₂NOH.",
+    refs="Cope, Foster, JACS 1949, 71, 3929.",
+    related="Hofmann Elimination, Chugaev",
+    functional_groups="amine, alkene")
+
+_nr("Corey-Chaykovsky Reaction",
+    aliases=["Corey-Chaykovsky", "dimethylsulfonium methylide"],
+    category="C-C Bond Formation", type_="Cyclopropanation/Epoxidation",
+    summary="Dimethylsulfonium methylide or dimethylsulfoxonium methylide → epoxides or cyclopropanes from C=O or C=C.",
+    conditions="Me3S⁺I⁻ + NaH (methylide → epoxides). Me3SO⁺I⁻ + NaH (ylide → cyclopropanes from enones).",
+    substrate="Aldehydes/ketones + methylide → epoxides. Enones + ylide → cyclopropanes.",
+    limitations="Methylide reacts faster (kinetic: epoxides). Ylide stabilized (thermodynamic: cyclopropanes).",
+    mechanism="Ylide attacks C=O → betaine → intramolecular displacement → epoxide (or C=C addition → cyclopropane).",
+    refs="Corey, Chaykovsky, JACS 1965, 87, 1353.",
+    related="Simmons-Smith, Sharpless",
+    functional_groups="aldehyde, ketone, epoxide, cyclopropane")
+
+_nr("Curtius Rearrangement",
+    aliases=["Curtius rearrangement", "Curtius degradation"],
+    category="Rearrangement", type_="Degradation",
+    summary="Acyl azides → isocyanates (with loss of N₂) → amines, carbamates, or ureas.",
+    conditions="RCON₃ heated (60–100 °C, toluene) or DPPA + Et₃N (one-pot from acid). Trap with ROH → carbamate.",
+    substrate="Carboxylic acids → amines (via isocyanate). One carbon shorter (Hofmann-type degradation).",
+    limitations="Azide handling hazards. Isocyanate intermediate is moisture-sensitive.",
+    mechanism="Acyl azide loses N₂ → nitrene? No: concerted [1,2]-shift (R migrates C→N) → isocyanate.",
+    refs="Curtius, Ber. 1890, 23, 3023.",
+    related="Hofmann, Lossen, Schmidt rearrangements",
+    functional_groups="carboxylic acid, azide, isocyanate, amine")
+
+_nr("Dakin Reaction",
+    aliases=["Dakin oxidation"],
+    category="Oxidation", type_="Phenol Oxidation",
+    summary="H₂O₂ oxidation of o/p-hydroxybenzaldehydes → catechols or hydroquinones.",
+    conditions="H₂O₂ (30%), NaOH, H₂O, rt–50 °C.",
+    substrate="o-Hydroxybenzaldehyde → catechol. p-Hydroxybenzaldehyde → hydroquinone.",
+    limitations="Only works with electron-rich (hydroxylated) arylaldehydes/ketones.",
+    mechanism="Baeyer-Villiger-like: HO₂⁻ attacks C=O → Criegee intermediate → aryl migrates → formate ester → hydrolysis → phenol.",
+    refs="Dakin, JACS 1909, 42, 477.",
+    related="Baeyer-Villiger",
+    functional_groups="aldehyde, phenol, catechol")
+
+_nr("Darzens Glycidic Ester Condensation",
+    aliases=["Darzens condensation", "Darzens reaction"],
+    category="C-C Bond Formation", type_="Condensation",
+    summary="α-Halo esters + aldehydes/ketones → glycidic esters (α,β-epoxy esters).",
+    conditions="NaOEt or KOtBu, Et₂O or THF, 0 °C → rt.",
+    substrate="α-Chloro esters + aldehydes → glycidic esters. Decarboxylation gives aldehydes (homologation).",
+    limitations="trans-selective. Competing Claisen condensation with excess base.",
+    mechanism="Base → enolate of α-halo ester → aldol with aldehyde → β-hydroxy-α-halo ester → intramolecular SN2 → epoxide.",
+    refs="Darzens, Compt. Rend. 1904, 139, 1214.",
+    related="Aldol, Reformatsky, Corey-Chaykovsky",
+    functional_groups="ester, aldehyde, epoxide")
+
+_nr("Dieckmann Cyclization",
+    aliases=["Dieckmann condensation"],
+    category="C-C Bond Formation", type_="Intramolecular Condensation",
+    summary="Intramolecular Claisen condensation of diesters → cyclic β-keto esters.",
+    conditions="NaOEt/EtOH or NaH/THF, reflux. Workup with acid.",
+    substrate="Diesters → 5- or 6-membered cyclic β-keto esters. 7-membered rings require high dilution.",
+    limitations="5,6-rings only without special conditions. Requires two ester groups.",
+    mechanism="Intramolecular enolate attacks second ester → ring closure → elimination of alkoxide.",
+    refs="Dieckmann, Ber. 1894, 27, 102.",
+    related="Claisen condensation, Aldol",
+    functional_groups="ester, β-keto ester, cyclic")
+
+_nr("Doering-LaFlamme Allene Synthesis",
+    aliases=["Doering-LaFlamme"],
+    category="C-C Bond Formation", type_="Allene Formation",
+    summary="Cyclopropanation of alkenes followed by ring opening to allenes using alkyllithium.",
+    conditions="CHBr₃/KOtBu → gem-dibromocyclopropane, then nBuLi/Et₂O → allene.",
+    substrate="Alkenes → allenes via gem-dihalocyclopropane intermediate.",
+    limitations="Requires gem-dihalocyclopropane. Competing elimination side products.",
+    mechanism="Carbenoid cyclopropanation → gem-dibromocyclopropane → nBuLi eliminates → carbenoid → ring opens → allene.",
+    refs="Doering, LaFlamme, Tetrahedron 1958, 2, 75.",
+    related="Simmons-Smith, Corey-Fuchs",
+    functional_groups="alkene, allene, cyclopropane")
+
+_nr("Enders SAMP/RAMP Hydrazones",
+    aliases=["SAMP hydrazone", "RAMP hydrazone", "Enders asymmetric alkylation"],
+    category="C-C Bond Formation", type_="Asymmetric α-Alkylation",
+    summary="Chiral hydrazones enable asymmetric α-alkylation of ketones/aldehydes.",
+    conditions="Ketone + SAMP → hydrazone, LDA, alkyl halide, then O₃ or MeI/LiAlH₄ to cleave.",
+    substrate="Ketones, aldehydes → α-alkylated products with >95% ee.",
+    limitations="Requires chiral auxiliary attachment/removal. Multi-step.",
+    mechanism="SAMP forms hydrazone → LDA → aza-enolate → alkylation anti to methoxymethyl → cleave auxiliary.",
+    refs="Enders, Eichenauer, Angew. Chem. Int. Ed. 1976, 15, 549.",
+    related="Evans oxazolidinone, Myers auxiliary",
+    functional_groups="ketone, hydrazone, alkyl halide")
+
+_nr("Eschweiler-Clarke Reaction",
+    aliases=["Eschweiler-Clarke", "reductive methylation"],
+    category="C-N Bond Formation", type_="N-Methylation",
+    summary="Exhaustive N-methylation of primary/secondary amines using HCHO/HCO₂H.",
+    conditions="HCHO (excess), HCO₂H, 80–100 °C. Gives tertiary amines (no quaternization).",
+    substrate="1° amines → 3° amines (dimethylated). 2° amines → 3° amines (monomethylated).",
+    limitations="Cannot make quaternary salts. Over-alkylation to NMe₂ with 1° amines.",
+    mechanism="Iminium formation with HCHO → formate reduces iminium (Leuckart-Wallach mechanism).",
+    refs="Eschweiler, Ber. 1905, 38, 880. Clarke, Gillespie, JACS 1933, 55, 4571.",
+    related="Reductive amination, Leuckart-Wallach",
+    functional_groups="amine, formaldehyde")
+
+_nr("Evans Aldol Reaction",
+    aliases=["Evans aldol", "Evans oxazolidinone"],
+    category="C-C Bond Formation", type_="Asymmetric Aldol",
+    summary="Chiral oxazolidinone auxiliaries give syn-aldol products with high diastereoselectivity.",
+    conditions="N-Acyloxazolidinone + Bu₂BOTf, Et₃N, –78 °C → add RCHO. Then LiOH/H₂O₂ or LiOBn cleavage.",
+    substrate="Propionyl oxazolidinone + aldehyde → syn-β-hydroxy acid derivatives (>95:5 dr, >98% ee).",
+    limitations="Stoichiometric chiral auxiliary (recoverable). Extra steps for attachment/cleavage.",
+    mechanism="B-enolate (Z) → Zimmerman-Traxler 6-membered TS → syn selectivity via chair TS with auxiliary shielding one face.",
+    refs="Evans, Bartroli, Shih, JACS 1981, 103, 2127.",
+    related="Aldol, Mukaiyama, Crimmins",
+    functional_groups="aldehyde, β-hydroxy, oxazolidinone")
+
+_nr("Favorskii Rearrangement",
+    aliases=["Favorskii rearrangement"],
+    category="Rearrangement", type_="Ring Contraction",
+    summary="α-Halo ketones + base → carboxylic acids or esters via cyclopropanone intermediate.",
+    conditions="α-Haloketone + NaOH or NaOMe, then acid workup.",
+    substrate="α-Haloketones → carboxylic acids (ring contraction if cyclic).",
+    limitations="Requires α-halo ketone. Competing elimination.",
+    mechanism="Base → enolate → intramolecular displacement of halide → cyclopropanone → nucleophilic ring opening.",
+    refs="Favorskii, JRCS 1894, 26, 590.",
+    related="Benzilic acid rearrangement",
+    functional_groups="ketone, halide, carboxylic acid")
+
+_nr("Ferrier Rearrangement",
+    aliases=["Ferrier rearrangement", "Ferrier glycosylation"],
+    category="Substitution", type_="Glycosylation",
+    summary="Lewis acid-catalyzed allylic rearrangement of glycals → 2,3-unsaturated glycosides.",
+    conditions="Glycal + nucleophile + BF₃·Et₂O or SnCl₄, CH₂Cl₂, 0 °C to rt.",
+    substrate="Glycals (2,3-unsaturated sugars) + ROH, TMSN₃, etc → C-1 glycosides with C2-C3 unsaturation.",
+    limitations="α/β selectivity depends on conditions. Requires glycal substrate.",
+    mechanism="Lewis acid activates C-3 OAc leaving group → allylic oxocarbenium → nucleophilic attack at C-1.",
+    refs="Ferrier, Prasad, J. Chem. Soc. C 1969, 570.",
+    related="Koenigs-Knorr, Schmidt glycosylation",
+    functional_groups="glycal, glycoside, alcohol")
+
+_nr("Hantzsch Pyridine Synthesis",
+    aliases=["Hantzsch synthesis", "Hantzsch pyridine"],
+    category="Heterocycle Formation", type_="Multicomponent",
+    summary="One-pot synthesis of 1,4-dihydropyridines from aldehyde + β-ketoester + ammonia.",
+    conditions="2 eq β-ketoester + aldehyde + NH₃ (or NH₄OAc), EtOH, reflux. Then oxidize (HNO₃ or DDQ) → pyridine.",
+    substrate="Aldehydes + β-keto esters + ammonia → 1,4-dihydropyridines → pyridines.",
+    limitations="Limited substitution patterns. Symmetric products from self-condensation.",
+    mechanism="Knoevenagel + enamine formation → cyclocondensation → 1,4-DHP → aromatize to pyridine.",
+    refs="Hantzsch, Ber. 1881, 14, 1637.",
+    related="Chichibabin, Paal-Knorr",
+    functional_groups="aldehyde, ester, pyridine")
+
+_nr("Hiyama-Denmark Coupling",
+    aliases=["Denmark coupling", "Hiyama-Denmark"],
+    category="C-C Bond Formation", type_="Cross-Coupling",
+    summary="Pd-catalyzed coupling of organosilanes with aryl halides, activated by fluoride or Lewis base.",
+    conditions="ArX + R-SiMe₃ or R-Si(OR)₃, Pd(0), TBAF or KF, THF.",
+    substrate="Aryl/vinyl halides/triflates + vinyl/aryl silanes → biaryls, dienes.",
+    limitations="Requires fluoride activation. Organosilanes less reactive than boronic acids.",
+    mechanism="Oxidative addition → fluoride activates Si (pentacoordinate) → transmetalation → reductive elimination.",
+    refs="Hiyama, Hatanaka, Pure Appl. Chem. 1994, 66, 1471. Denmark, Regens, Acc. Chem. Res. 2008, 41, 1486.",
+    related="Suzuki, Hiyama, Stille",
+    functional_groups="aryl halide, silane, biaryl")
+
+_nr("Hofmann Elimination",
+    aliases=["Hofmann elimination"],
+    category="Functional Group Interconversion", type_="Elimination",
+    summary="Quaternary ammonium hydroxides undergo E2 elimination to give less-substituted (Hofmann) alkene.",
+    conditions="Amine → MeI (exhaust. methylation) → Me₃N⁺ → Ag₂O/H₂O → heat (100–200 °C).",
+    substrate="Quaternary ammonium salts → terminal/less-substituted alkenes (anti-Zaitsev).",
+    limitations="Multi-step. High temperature. Competing Zaitsev product.",
+    mechanism="E2 with bulky NMe₃ leaving group → anti-periplanar → less-substituted alkene preferred (steric).",
+    refs="Hofmann, Annalen 1851, 78, 253.",
+    related="Cope Elimination, Zaitsev",
+    functional_groups="amine, alkene")
+
+_nr("Horner Reaction",
+    aliases=["Horner reaction", "Horner-Wittig"],
+    category="C-C Bond Formation", type_="Olefination",
+    summary="Phosphine oxide-stabilized carbanions react with aldehydes/ketones → alkenes.",
+    conditions="Ph₃P=O-stabilized carbanion + RCHO, nBuLi, THF, –78 °C → rt.",
+    substrate="Phosphine oxides + aldehydes → (E)-alkenes. Phosphine oxide byproduct easily removed.",
+    limitations="Less reactive than Wittig ylides. Requires strong base.",
+    mechanism="Like Wittig but with P(O)Ph₂: betaine → oxaphosphetane → alkene + Ph₂P(O)OH (water soluble).",
+    refs="Horner, Hoffmann, Wippel, Ber. 1958, 91, 61.",
+    related="HWE, Wittig, Julia Olefination",
+    functional_groups="phosphine oxide, aldehyde, alkene")
+
+_nr("Ireland-Claisen Rearrangement",
+    aliases=["Ireland-Claisen"],
+    category="Rearrangement", type_="[3,3]-Sigmatropic",
+    summary="Silyl ketene acetal from ester enolate undergoes [3,3] sigmatropic rearrangement → γ,δ-unsaturated acid.",
+    conditions="Ester + LDA → enolate + TMSCl → silyl ketene acetal → heat (60–100 °C) → carboxylic acid.",
+    substrate="Allyl esters → γ,δ-unsaturated carboxylic acids. E/Z enolate geometry → syn/anti selectivity.",
+    limitations="Requires allyl ester substrate. Stereocontrol via enolate geometry.",
+    mechanism="[3,3]-sigmatropic via chair TS: allyl vinyl ether rearrangement. Z-enolate → syn, E-enolate → anti.",
+    refs="Ireland, Mueller, Willard, JACS 1976, 98, 2868.",
+    related="Claisen, Johnson-Claisen, Eschenmoser-Claisen",
+    functional_groups="ester, carboxylic acid, alkene")
+
+_nr("Knoevenagel Condensation",
+    aliases=["Knoevenagel"],
+    category="C-C Bond Formation", type_="Condensation",
+    summary="Aldol-like condensation of aldehydes with active methylene compounds (malonate, cyanoacetate, etc.).",
+    conditions="RCHO + CH₂(CO₂Et)₂ or CH₂(CN)CO₂Et, piperidine or pyridine cat., EtOH, reflux. Doebner: decarboxylation in situ.",
+    substrate="Aldehydes + active methylene → α,β-unsaturated diesters/nitriles. Doebner variant → cinnamic acids.",
+    limitations="Ketones generally unreactive. Needs activated methylene (pKa < 20).",
+    mechanism="Base → carbanion → aldol addition → dehydration → alkene. Doebner: in situ decarboxylation → monoester.",
+    refs="Knoevenagel, Ber. 1898, 31, 2596.",
+    related="Aldol, HWE, Henry",
+    functional_groups="aldehyde, malonate, α,β-unsaturated ester")
+
+_nr("Kolbe Electrolysis",
+    aliases=["Kolbe electrolysis", "Kolbe reaction"],
+    category="C-C Bond Formation", type_="Electrochemistry",
+    summary="Electrolytic oxidative decarboxylation of carboxylate salts → alkane dimers (R-R).",
+    conditions="RCO₂Na in H₂O or MeOH, Pt electrodes, constant current. Also: Hofer-Moest (forms alcohol/alkene).",
+    substrate="Carboxylic acid salts → symmetric alkanes (R-R coupling). Long-chain fatty acids work well.",
+    limitations="Symmetric coupling only. Competing Hofer-Moest oxidation.",
+    mechanism="Anodic: RCO₂⁻ → RCO₂• → R• + CO₂ → radical coupling → R-R.",
+    refs="Kolbe, Annalen 1849, 69, 257.",
+    related="Barton decarboxylation",
+    functional_groups="carboxylic acid, alkane")
+
+_nr("Kulinkovich Reaction",
+    aliases=["Kulinkovich", "Kulinkovich cyclopropanation"],
+    category="C-C Bond Formation", type_="Cyclopropanation",
+    summary="Ti(OiPr)₄/EtMgBr-mediated conversion of esters → cyclopropanols.",
+    conditions="Ester + EtMgBr (2 eq), Ti(OiPr)₄ (cat.), Et₂O, 0 °C → rt.",
+    substrate="Esters → 1-substituted cyclopropanols. Also amides (de Meijere variant) → cyclopropylamines.",
+    limitations="Only with EtMgBr (or similar). Difficult with sterically hindered esters.",
+    mechanism="EtMgBr + Ti(OiPr)₄ → titanacyclopropane → inserts into C=O of ester → oxatitanacycle → ring closure → cyclopropanol.",
+    refs="Kulinkovich, Sviridov, Vasilevskii, Synthesis 1991, 234.",
+    related="Simmons-Smith, Corey-Chaykovsky",
+    functional_groups="ester, cyclopropane, alcohol")
+
+_nr("Lawesson's Reagent",
+    aliases=["Lawesson reagent", "thionation"],
+    category="Functional Group Interconversion", type_="Thionation",
+    summary="C=O → C=S conversion (thionation) of amides, esters, ketones, and lactones.",
+    conditions="Lawesson's reagent (0.5–1.0 eq), toluene, 80–110 °C.",
+    substrate="Amides → thioamides. Ketones → thioketones. Esters → thioesters. Lactones → thiolactones.",
+    limitations="Harsh conditions. Over-thionation possible. Acidic conditions decompose reagent.",
+    mechanism="Lawesson's reagent ↔ dithiaphosphetane → [2+2] with C=O → 4-membered ring → cycloreversion → C=S + P=O.",
+    refs="Lawesson, Bull. Soc. Chim. Belg. 1978, 87, 229.",
+    related="P₄S₁₀",
+    functional_groups="amide, ketone, thioamide, thioketone")
+
+_nr("Lossen Rearrangement",
+    aliases=["Lossen rearrangement"],
+    category="Rearrangement", type_="Degradation",
+    summary="Activated hydroxamic acids → isocyanates via [1,2]-shift (like Curtius/Hofmann).",
+    conditions="Hydroxamic acid + activating agent (CDI, SOCl₂, p-TsCl) → isocyanate. Trap with ROH/H₂O.",
+    substrate="Hydroxamic acids → isocyanates → amines, carbamates, or ureas.",
+    limitations="Requires pre-formed hydroxamic acid + activation.",
+    mechanism="Activation of O-H → departure of leaving group → [1,2]-shift of R from C to N → isocyanate + byproduct.",
+    refs="Lossen, Annalen 1872, 161, 347.",
+    related="Curtius, Hofmann, Schmidt",
+    functional_groups="hydroxamic acid, isocyanate, amine")
+
+_nr("Luche Reduction",
+    aliases=["Luche reduction"],
+    category="Reduction", type_="Selective Reduction",
+    summary="1,2-selective reduction of α,β-unsaturated ketones using NaBH₄/CeCl₃.",
+    conditions="NaBH₄, CeCl₃·7H₂O, MeOH, 0 °C → rt. Quick reaction (minutes).",
+    substrate="Enones → allylic alcohols (1,2-reduction). Selective over 1,4-reduction.",
+    limitations="Only for α,β-unsaturated carbonyls. Not for isolated C=C.",
+    mechanism="CeCl₃ activates C=O (hard Lewis acid) → NaBH₄ delivers H⁻ to C=O (1,2) instead of conjugate (1,4).",
+    refs="Luche, JACS 1978, 100, 2226.",
+    related="NaBH₄, CBS, Meerwein-Ponndorf-Verley",
+    functional_groups="enone, allylic alcohol")
+
+_nr("Matteson Homologation",
+    aliases=["Matteson homologation"],
+    category="Homologation", type_="Boron Homologation",
+    summary="Iterative one-carbon homologation of boronic esters with high stereocontrol.",
+    conditions="R-B(pin) + CHCl₂Li (or ICH₂Cl/nBuLi) → α-chloroboronate → ZnCl₂/MgBr₂ stereospecific substitution.",
+    substrate="Boronic esters → homologated boronic esters, iteratively with stereocontrol.",
+    limitations="Requires careful handling of α-halocarbanions. Multi-step for complex targets.",
+    mechanism="Carbenoid inserts into C-B bond → α-haloboronate → 1,2-migration with inversion → new C-C bond.",
+    refs="Matteson, Mah, JACS 1982, 104, 4471.",
+    related="Suzuki, Aggarwal homologation",
+    functional_groups="boronic ester, alkyl halide")
+
+_nr("Michael Reaction",
+    aliases=["Michael addition", "conjugate addition", "1,4-addition"],
+    category="C-C Bond Formation", type_="Conjugate Addition",
+    summary="Nucleophilic 1,4-addition to α,β-unsaturated carbonyl compounds.",
+    conditions="Nucleophile + enone/enal, base (NaOEt, DBU, or organocatalyst), or CuLn for cuprate 1,4-addition.",
+    substrate="Malonates, enolates, or cuprates + enones → 1,5-dicarbonyls. Also aza-Michael (amines), oxa-Michael (alcohols).",
+    limitations="Competing 1,2-addition with hard nucleophiles. Regioselectivity control needed.",
+    mechanism="Deprotonation → carbanion attacks β-carbon of enone → enolate intermediate → protonation at α.",
+    refs="Michael, J. Prakt. Chem. 1887, 35, 349.",
+    related="Robinson annulation, Stetter, Mukaiyama-Michael",
+    functional_groups="enone, malonate, 1,5-dicarbonyl")
+
+_nr("Minisci Reaction",
+    aliases=["Minisci reaction", "Minisci radical addition"],
+    category="Radical", type_="Radical C-H Functionalization",
+    summary="Radical addition to protonated heteroaromatics (pyridine, quinoline, etc.) for C-H functionalization.",
+    conditions="Hetarene + RCO₃H or R-I + AgNO₃/persulfate, H₂SO₄ (acid), 60–80 °C.",
+    substrate="Pyridines, quinolines, isoquinolines → C-2/C-4 alkylated/acylated products. C-2 preferred.",
+    limitations="Regioselectivity can be poor. Mixtures of mono/disubstitution. Requires acid medium.",
+    mechanism="Radical generated (from acid, peroxide, or photoredox) → adds to protonated heterocycle → rearomatization.",
+    refs="Minisci, Bernardi, Bertini, Synthesis 1971, 650.",
+    related="Giese radical addition",
+    functional_groups="pyridine, radical, carboxylic acid")
+
+_nr("Mukaiyama Aldol Reaction",
+    aliases=["Mukaiyama aldol", "Mukaiyama"],
+    category="C-C Bond Formation", type_="Lewis Acid Aldol",
+    summary="Lewis acid-catalyzed aldol of silyl enol ethers with aldehydes.",
+    conditions="Silyl enol ether + RCHO + TiCl₄ or BF₃·Et₂O, CH₂Cl₂, –78 °C. Asymmetric: chiral Cu(II), Sn(II), or B catalysts.",
+    substrate="Silyl enol ethers + aldehydes → β-hydroxy ketones. Vinylogous variant for γ-addition.",
+    limitations="Requires pre-formed silyl enol ether. Lewis acid can racemize product.",
+    mechanism="Lewis acid activates aldehyde → nucleophilic addition of silyl enol ether → β-silyloxy ketone → deprotect.",
+    refs="Mukaiyama, Narasaka, Banno, Chem. Lett. 1973, 2, 1011.",
+    related="Aldol, Evans, Masamune",
+    functional_groups="silyl enol ether, aldehyde, β-hydroxy ketone")
+
+_nr("Myers Asymmetric Alkylation",
+    aliases=["Myers alkylation", "pseudoephedrine auxiliary"],
+    category="C-C Bond Formation", type_="Asymmetric Alkylation",
+    summary="Pseudoephedrine amide auxiliaries for highly enantioselective α-alkylation.",
+    conditions="Pseudoephedrine amide + LDA + LiCl, THF, 0 °C → alkyl halide. Cleave: LiOH/H₂O₂ or LiNH₂/NH₃(l).",
+    substrate="Amides → α-alkylated carboxylic acids with >95% ee. Broad substrate scope.",
+    limitations="Stoichiometric auxiliary. Extra steps for attachment/cleavage.",
+    mechanism="LDA/LiCl → chelated (Z)-enolate → alkylation on exposed face → high ee.",
+    refs="Myers, Yang, Chen, Cebulak, JACS 1997, 119, 6496.",
+    related="Evans, Enders, Oppolzer",
+    functional_groups="amide, alkyl halide, carboxylic acid")
+
+_nr("Negishi Coupling",
+    aliases=["Negishi coupling"],
+    category="C-C Bond Formation", type_="Cross-Coupling",
+    summary="Pd or Ni-catalyzed cross-coupling of organozinc reagents with organic halides.",
+    conditions="R-ZnX + R'-X, Pd(PPh₃)₄ or Pd(dba)₂/ligand, THF, 0 °C → rt. Very high functional group tolerance.",
+    substrate="Aryl, vinyl, alkyl zinc + aryl/vinyl halides/triflates → coupled products.",
+    limitations="Organozinc preparation requires anhydrous conditions. Less atom-economical than Suzuki.",
+    mechanism="Oxidative addition of R'-X to Pd(0) → transmetalation with R-ZnX → reductive elimination → R-R' + Pd(0).",
+    refs="Negishi, King, Okukado, J. Org. Chem. 1977, 42, 1821.",
+    related="Suzuki, Kumada, Stille, Heck",
+    functional_groups="organozinc, aryl halide, biaryl")
+
+_nr("Nozaki-Hiyama-Kishi Reaction",
+    aliases=["NHK reaction", "Nozaki-Hiyama-Kishi"],
+    category="C-C Bond Formation", type_="Allylation/Carbonyl Addition",
+    summary="CrCl₂-mediated coupling of vinyl/allyl halides with aldehydes (highly chemoselective for aldehyde over ketone).",
+    conditions="CrCl₂ (excess, 2–6 eq) + NiCl₂ (cat.), DMF, rt. Modern: Fürstner's cat. Cr + Mn reductant.",
+    substrate="Vinyl iodides/bromides + aldehydes → allylic alcohols. Remarkable aldehyde selectivity.",
+    limitations="Stoichiometric Cr (toxic, environmentally problematic). Catalytic versions exist but less developed.",
+    mechanism="Cr(II) reduces vinyl halide → vinyl-Cr(III) → nucleophilic addition to aldehyde → allylic alcohol + Cr(III) salt.",
+    refs="Nozaki, Oshima, Takai, JACS 1977, 99, 3532. Kishi: application to palytoxin.",
+    related="Grignard, Barbier",
+    functional_groups="vinyl halide, aldehyde, allylic alcohol")
+
+_nr("Passerini Reaction",
+    aliases=["Passerini reaction", "Passerini 3CR"],
+    category="C-C Bond Formation", type_="Multicomponent",
+    summary="Three-component reaction of isocyanide + aldehyde + carboxylic acid → α-acyloxyamide.",
+    conditions="R-NC + R'CHO + R''CO₂H, CH₂Cl₂ or MeOH, rt, 24–48 h.",
+    substrate="Isocyanides + aldehydes + carboxylic acids → α-acyloxyamides. Huge diversity-oriented potential.",
+    limitations="Isocyanide odor. Limited stereocontrol (racemic).",
+    mechanism="Aldehyde + acid → H-bonded complex → isocyanide inserts into C=O → α-adduct → acyl migration → product.",
+    refs="Passerini, Gazz. Chim. Ital. 1921, 51, 126.",
+    related="Ugi, Biginelli",
+    functional_groups="isocyanide, aldehyde, carboxylic acid, amide")
+
+_nr("Paternò-Büchi Reaction",
+    aliases=["Paterno-Buchi", "Paternò-Büchi"],
+    category="Cycloaddition", type_="[2+2] Photocycloaddition",
+    summary="Photochemical [2+2] cycloaddition of carbonyl compounds with alkenes → oxetanes.",
+    conditions="C=O + alkene, hν (UV, 254–350 nm), solvent (benzene, acetone, CH₂Cl₂).",
+    substrate="Aldehydes/ketones + electron-rich alkenes → oxetanes. Regiochemistry: head-to-head preferred.",
+    limitations="Requires UV irradiation. Competing [2+2] at C=C. Product strain (4-membered ring).",
+    mechanism="Carbonyl excited (S₁ or T₁ via ISC) → addition to alkene → diradical → ring closure → oxetane.",
+    refs="Paternò, Chieffi, Gazz. Chim. Ital. 1909, 39, 341. Büchi, Inman, Lipinsky, JACS 1954, 76, 4327.",
+    related="[2+2] photocycloaddition, Norrish",
+    functional_groups="carbonyl, alkene, oxetane")
+
+_nr("Petasis Reaction",
+    aliases=["Petasis borono-Mannich", "Petasis reaction"],
+    category="C-C Bond Formation", type_="Multicomponent",
+    summary="Three-component coupling of amine + aldehyde + boronic acid → substituted amine.",
+    conditions="R₂NH + RCHO + ArB(OH)₂, CH₂Cl₂ or MeOH, rt. No metal catalyst needed.",
+    substrate="Amines + glyoxylic acid or salicylaldehydes + boronic acids → α-amino acids, aminophenols.",
+    limitations="Best with glyoxylic acid or salicylaldehydes (need α-hydroxy). Aliphatic boronic acids less reactive.",
+    mechanism="Imine/iminium formation → boronate coordinates to adjacent OH → intramolecular transfer of aryl from B to C.",
+    refs="Petasis, Akritopoulou, Tetrahedron Lett. 1993, 34, 583.",
+    related="Mannich, Ugi, Suzuki",
+    functional_groups="amine, aldehyde, boronic acid")
+
+_nr("Pictet-Spengler Reaction",
+    aliases=["Pictet-Spengler"],
+    category="Heterocycle Formation", type_="Ring Closure",
+    summary="Acid-catalyzed condensation of β-arylethylamines with aldehydes → tetrahydroisoquinolines/β-carbolines.",
+    conditions="Tryptamine or PEA derivative + RCHO, TFA or AcOH, CH₂Cl₂ or MeOH, rt–reflux.",
+    substrate="Tryptamines + aldehydes → β-carbolines. PEA + aldehydes → tetrahydroisoquinolines.",
+    limitations="Electron-poor arenes are sluggish. Stereocontrol challenging (chiral phosphoric acid catalysts).",
+    mechanism="Iminium formation → electrophilic cyclization → Wheland intermediate → rearomatization.",
+    refs="Pictet, Spengler, Ber. 1911, 44, 2030.",
+    related="Bischler-Napieralski, Mannich",
+    functional_groups="amine, aldehyde, isoquinoline, β-carboline")
+
+_nr("Pinner Reaction",
+    aliases=["Pinner synthesis", "Pinner reaction"],
+    category="Functional Group Interconversion", type_="Nitrile Conversion",
+    summary="Acid-catalyzed conversion of nitriles to imino esters (Pinner salts), then to esters, amidines, or amides.",
+    conditions="R-CN + ROH + dry HCl(g) → Pinner salt (imidate·HCl). Then: H₂O → ester, NH₃ → amidine, R'OH → orthoester.",
+    substrate="Nitriles → imino esters → esters, amidines, amides, orthoesters.",
+    limitations="Anhydrous HCl required. Pinner salt hydrolysis must be controlled.",
+    mechanism="HCl protonates nitrile → alcohol attacks activated N≡C → iminium → Pinner salt. Hydrolysis → ester.",
+    refs="Pinner, Klein, Ber. 1877, 10, 1889.",
+    related="Ritter reaction",
+    functional_groups="nitrile, ester, amidine")
+
+_nr("Prins Reaction",
+    aliases=["Prins reaction", "Prins cyclization"],
+    category="C-C Bond Formation", type_="Carbonyl-Ene/Cyclization",
+    summary="Acid-catalyzed addition of aldehydes to alkenes → homoallylic alcohols, 1,3-dioxanes, or tetrahydropyrans.",
+    conditions="R-CH=CH₂ + RCHO, Lewis acid (BF₃, SnCl₄, InBr₃), CH₂Cl₂ or neat, –78 °C to rt.",
+    substrate="Alkenes + aldehydes → homoallylic alcohols (kinetic) or tetrahydropyrans (cyclization). Prins-type cascade for natural products.",
+    limitations="Product depends on conditions (alcohol vs THP vs dioxane). Competing polymerization.",
+    mechanism="Lewis acid activates aldehyde → ene reaction or carbocation formation → C-C bond → THP formation or trapping.",
+    refs="Prins, Chem. Weekblad 1919, 16, 1072.",
+    related="Conia-ene, Mukaiyama",
+    functional_groups="alkene, aldehyde, tetrahydropyran, alcohol")
+
+_nr("Ramberg-Bäcklund Reaction",
+    aliases=["Ramberg-Backlund", "Ramberg-Bäcklund"],
+    category="C-C Bond Formation", type_="Sulfone Elimination",
+    summary="α-Halo sulfones → alkenes via episulfone intermediate with extrusion of SO₂.",
+    conditions="α-Haloalkylsulfone + KOtBu or NaOH, or Meyers' conditions (KOH/Al₂O₃, CHCl₃, rt).",
+    substrate="α-Haloalkylsulfones → alkenes (with loss of SO₂). Meyers conditions very mild.",
+    limitations="Requires α-halo sulfone precursor. E/Z control limited.",
+    mechanism="Base abstracts α-H → carbanion displaces halide → episulfone → cheletropic loss of SO₂ → alkene.",
+    refs="Ramberg, Bäcklund, Arkiv Kemi 1940, 13A, 1.",
+    related="Julia Olefination, Peterson",
+    functional_groups="sulfone, alkene, halide")
+
+_nr("Ring-Closing Metathesis",
+    aliases=["RCM", "ring-closing metathesis"],
+    category="C-C Bond Formation", type_="Metathesis",
+    summary="Ru-catalyzed intramolecular olefin metathesis to form carbocyclic/heterocyclic rings.",
+    conditions="Grubbs I (PCy₃), Grubbs II (NHC), or Hoveyda-Grubbs cat., CH₂Cl₂ or toluene, 40 °C, dilute. Ethylene removed under vacuum/N₂.",
+    substrate="Dienes → 5–8-membered rings (best for 5, 6). Macrocycles also possible at high dilution.",
+    limitations="Ring strain limits small rings (<5). Catalyst poisoning by N, S, P. Dilution needed for macro-RCM.",
+    mechanism="Ru=CHR → [2+2] with terminal alkene → metallacyclobutane → retro [2+2] → new Ru=CH → intramolecular closure → product + CH₂=CH₂.",
+    refs="Grubbs, JACS 1995, 117, 5503. Schrock, Murdzek, JACS 1990, 112, 3875.",
+    related="Olefin metathesis, ROMP, CM",
+    functional_groups="diene, alkene, ring")
+
+_nr("Ritter Reaction",
+    aliases=["Ritter reaction"],
+    category="C-N Bond Formation", type_="Amide Formation",
+    summary="Acid-catalyzed addition of nitriles to carbocations (from alkenes/alcohols) → amides.",
+    conditions="R-OH or R-CH=CH₂ + R'CN, H₂SO₄ or BF₃·Et₂O, 0 °C → rt. Then H₂O workup → amide.",
+    substrate="Tertiary alcohols/alkenes + nitriles → N-tert-alkyl amides. Good for tert-amines (hydrolysis).",
+    limitations="Requires stable carbocation (3°, benzylic, allylic). 1° and 2° give poor results.",
+    mechanism="Acid → carbocation → attacks nitrile N → nitrilium → H₂O adds → amide (tautomerize).",
+    refs="Ritter, Minieri, JACS 1948, 70, 4045.",
+    related="Pinner, Beckmann",
+    functional_groups="nitrile, alcohol, amide")
+
+_nr("Robinson Annulation",
+    aliases=["Robinson annulation"],
+    category="C-C Bond Formation", type_="Annulation",
+    summary="Tandem Michael addition + intramolecular aldol → cyclohexenone ring construction.",
+    conditions="Ketone + methyl vinyl ketone, NaOH or KOH, EtOH/H₂O, rt → reflux. Also: Hajos-Parrish (proline-catalyzed).",
+    substrate="Ketones + MVK → 2-cyclohexenones. Key step in steroid synthesis (Hajos-Parrish-Eder-Sauer-Wiechert).",
+    limitations="Polymerization of MVK. Regiochemistry with unsymmetrical ketones.",
+    mechanism="Michael addition of enolate to enone → 1,5-diketone → intramolecular aldol → β-hydroxy ketone → dehydration → cyclohexenone.",
+    refs="Robinson, J. Chem. Soc. 1935, 1604.",
+    related="Michael, Aldol, Hajos-Parrish",
+    functional_groups="ketone, enone, cyclohexenone")
+
+_nr("Roush Allylboration",
+    aliases=["Roush allylboration", "allylboration"],
+    category="C-C Bond Formation", type_="Allylation",
+    summary="Chiral allylboronates add to aldehydes with high diastereo- and enantioselectivity.",
+    conditions="Chiral tartrate allylboronate + RCHO, toluene, –78 °C. Also: Brown (Ipc₂B), Roush (DIPT tartrate).",
+    substrate="Aldehydes → homoallylic alcohols with up to >95% ee. E-crotyl → anti, Z-crotyl → syn.",
+    limitations="Requires chiral auxiliary on boron. Stoichiometric chiral reagent.",
+    mechanism="6-membered Zimmerman-Traxler TS: aldehyde coordinates B, allyl transferred via chair-like TS → homoallylic alcohol.",
+    refs="Roush, Walts, Hoong, JACS 1985, 107, 8186.",
+    related="Brown allylation, Matteson, crotylation",
+    functional_groups="aldehyde, allylboron, homoallylic alcohol")
+
+_nr("Sakurai-Hosomi Allylation",
+    aliases=["Sakurai allylation", "Hosomi-Sakurai"],
+    category="C-C Bond Formation", type_="Allylation",
+    summary="Lewis acid-mediated allylation of aldehydes/ketones with allylsilanes.",
+    conditions="Allyl-TMS + RCHO + TiCl₄ or BF₃·Et₂O, CH₂Cl₂, –78 °C.",
+    substrate="Aldehydes, ketones, acetals → homoallylic alcohols. Good functional group tolerance.",
+    limitations="Requires Lewis acid. Less enantioselective than allylborations (unless chiral Lewis acid).",
+    mechanism="Lewis acid activates C=O → allylsilane attacks → SE2' → homoallylic alcohol + TMS-X.",
+    refs="Hosomi, Sakurai, Tetrahedron Lett. 1976, 17, 1295.",
+    related="Crotylation, Roush, Mukaiyama aldol",
+    functional_groups="allylsilane, aldehyde, homoallylic alcohol")
+
+_nr("Simmons-Smith Cyclopropanation",
+    aliases=["Simmons-Smith", "Simmons-Smith reaction"],
+    category="Cycloaddition", type_="Cyclopropanation",
+    summary="Zn-carbenoid cyclopropanation of alkenes using CH₂I₂/Zn-Cu.",
+    conditions="CH₂I₂ + Zn-Cu couple or Et₂Zn (Furukawa mod.), Et₂O or CH₂Cl₂, 0 °C → rt. Charette: directed with chiral bisoxazoline.",
+    substrate="Alkenes → cyclopropanes. Directed by adjacent OH (syn delivery). Stereospecific (retention of alkene geometry).",
+    limitations="Methylene transfer only (no substituted carbenoids easily). Zn waste.",
+    mechanism="ICH₂ZnI (Zn carbenoid) → [2+1] delivery of CH₂ to alkene face → cyclopropane. Butterfly/concerted TS.",
+    refs="Simmons, Smith, JACS 1958, 80, 5323.",
+    related="Corey-Chaykovsky, Kulinkovich, Doering-LaFlamme",
+    functional_groups="alkene, cyclopropane")
+
+_nr("Stetter Reaction",
+    aliases=["Stetter reaction", "NHC-catalyzed 1,4-addition"],
+    category="C-C Bond Formation", type_="Umpolung Conjugate Addition",
+    summary="NHC-catalyzed umpolung: aldehyde → acyl anion equivalent → 1,4-addition to Michael acceptors → 1,4-diketones.",
+    conditions="Aldehyde + enone + thiazolium/triazolium salt (NHC) + Et₃N, EtOH, reflux. Intramolecular: Stetter cyclization.",
+    substrate="Aldehydes + Michael acceptors → 1,4-dicarbonyls. Intramolecular for chromanones, etc.",
+    limitations="Intermolecular often low yielding. Self-condensation of aldehyde (benzoin). Asymmetric variants developing.",
+    mechanism="NHC adds to aldehyde → Breslow intermediate (acyl anion equiv.) → conjugate addition → 1,4-product → NHC released.",
+    refs="Stetter, Angew. Chem. Int. Ed. 1976, 15, 639.",
+    related="Benzoin condensation, Michael",
+    functional_groups="aldehyde, enone, 1,4-diketone")
+
+_nr("Stork Enamine Alkylation",
+    aliases=["Stork enamine", "enamine alkylation"],
+    category="C-C Bond Formation", type_="α-Alkylation",
+    summary="Enamines as nucleophiles for α-alkylation/acylation of ketones under mild conditions.",
+    conditions="Ketone + 2° amine (pyrrolidine) → enamine → alkyl/acyl halide → hydrolysis → α-substituted ketone.",
+    substrate="Ketones → α-alkylated or α-acylated ketones. Regioselective (less-substituted enamine preferred).",
+    limitations="Less-substituted enamine forms preferentially (kinetic). Competing N-alkylation.",
+    mechanism="Amine + ketone → enamine (C=C-N) → C-alkylation with electrophile → iminium → hydrolysis → ketone.",
+    refs="Stork, Terrell, Szmuszkovicz, JACS 1954, 76, 2029.",
+    related="Enders SAMP/RAMP, organocatalysis",
+    functional_groups="ketone, amine, alkyl halide")
+
+_nr("Strecker Synthesis",
+    aliases=["Strecker synthesis", "Strecker amino acid synthesis"],
+    category="C-C Bond Formation", type_="Multicomponent",
+    summary="Aldehyde + ammonia + HCN → α-aminonitrile → α-amino acid (hydrolysis).",
+    conditions="RCHO + NH₄Cl + NaCN (or TMSCN), H₂O or MeOH, 0 °C → rt. Asymmetric: chiral thiourea or phosphoric acid cat.",
+    substrate="Aldehydes → α-amino acids (after hydrolysis of nitrile). Asymmetric variants give high ee.",
+    limitations="HCN toxicity. Racemic unless chiral catalyst used.",
+    mechanism="Imine formation (RCHO + NH₃) → cyanide attacks imine → α-aminonitrile → acid hydrolysis → amino acid.",
+    refs="Strecker, Annalen 1850, 75, 27.",
+    related="Ugi, Passerini",
+    functional_groups="aldehyde, amine, amino acid, nitrile")
+
+_nr("Takai Olefination",
+    aliases=["Takai olefination", "Takai reaction"],
+    category="C-C Bond Formation", type_="Olefination",
+    summary="CrCl₂/CHI₃ converts aldehydes to (E)-vinyl iodides selectively.",
+    conditions="RCHO + CHI₃, CrCl₂ (excess), THF, 0 °C → rt. Also CHBr₃ for vinyl bromides.",
+    substrate="Aldehydes → (E)-vinyl iodides. Excellent E-selectivity (>95:5).",
+    limitations="Stoichiometric Cr(II) (toxic). Not for ketones.",
+    mechanism="CrCl₂ reduces CHI₃ → Cr-carbenoid → adds to aldehyde → vinyl metal → β-elimination → (E)-vinyl iodide.",
+    refs="Takai, Nitta, Utimoto, JACS 1986, 108, 7408.",
+    related="NHK, Wittig, Still-Gennari",
+    functional_groups="aldehyde, vinyl iodide")
+
+_nr("Tiffeneau-Demjanov Rearrangement",
+    aliases=["Tiffeneau-Demjanov", "ring expansion"],
+    category="Rearrangement", type_="Ring Expansion",
+    summary="Cyclic α-amino ketones → ring-expanded ketones (+1 carbon) via diazotization.",
+    conditions="α-Amino ketone + NaNO₂/AcOH → α-diazo ketone → N₂ loss → ring expansion.",
+    substrate="Cyclopentanone → cyclohexanone, cyclohexanone → cycloheptanone, etc.",
+    limitations="Competing Wolff rearrangement. Requires α-amino ketone.",
+    mechanism="Diazotization → α-diazo ketone → N₂ leaves → 1,2-shift of C-C bond adjacent to carbocation → ring-expanded ketone.",
+    refs="Tiffeneau, Weill, Tchoubar, Compt. Rend. 1937, 205, 54.",
+    related="Beckmann, Baeyer-Villiger, Buchner",
+    functional_groups="ketone, amine, ring expansion")
+
+_nr("Ullmann Coupling",
+    aliases=["Ullmann coupling", "Ullmann reaction"],
+    category="C-C Bond Formation", type_="Cu-Mediated Coupling",
+    summary="Cu-mediated homo- or cross-coupling of aryl halides. Modern: Cu-catalyzed C-N, C-O, C-S coupling (Ullmann-type).",
+    conditions="Classical: 2 ArX + Cu powder, 200 °C. Modern: ArX + NuH, CuI (10%), diamine ligand, Cs₂CO₃, DMSO, 80 °C.",
+    substrate="Aryl halides → biaryls (classical). ArX + amines/phenols/thiols → C-N/C-O/C-S (modern Ullmann-Goldberg-Buchwald).",
+    limitations="Classical requires high T. Modern requires good ligand design for challenging substrates.",
+    mechanism="Classical: Cu(0) → oxidative addition → Cu(III)-Ar → second ArX → reductive elimination → Ar-Ar. Modern: Cu(I)/Cu(III) cycle.",
+    refs="Ullmann, Bielecki, Ber. 1901, 34, 2174.",
+    related="Buchwald-Hartwig, Chan-Lam, Suzuki",
+    functional_groups="aryl halide, biaryl, amine, phenol")
+
+_nr("Ugi Reaction",
+    aliases=["Ugi reaction", "Ugi 4CR", "Ugi multicomponent"],
+    category="C-C Bond Formation", type_="Multicomponent",
+    summary="Four-component reaction: amine + aldehyde + carboxylic acid + isocyanide → α-acylaminoamide.",
+    conditions="R₂NH + R'CHO + R''CO₂H + R'''NC, MeOH, rt, 24–48 h. Also: Ugi-3CR, Ugi-azide, Ugi-Heck cascades.",
+    substrate="Generates enormous molecular diversity from simple building blocks. Peptoid backbones, macrocycles.",
+    limitations="Isocyanide odor/toxicity. Racemic (chiral variants under development). Purification challenging.",
+    mechanism="Imine formation → protonation by acid → isocyanide attacks iminium → α-adduct → Mumm rearrangement → product.",
+    refs="Ugi, Steinbrückner, Angew. Chem. 1960, 72, 267.",
+    related="Passerini, Biginelli, Strecker",
+    functional_groups="amine, aldehyde, carboxylic acid, isocyanide, amide")
+
+_nr("Vilsmeier-Haack Formylation",
+    aliases=["Vilsmeier-Haack", "Vilsmeier formylation"],
+    category="C-C Bond Formation", type_="Electrophilic Formylation",
+    summary="POCl₃/DMF-mediated formylation of electron-rich arenes (phenols, anilines, heterocycles).",
+    conditions="DMF + POCl₃ (0 °C, form Vilsmeier reagent) → add substrate, 60–80 °C → aqueous workup → aldehyde.",
+    substrate="Electron-rich aromatics → aryl aldehydes. Pyrroles, indoles, phenol ethers, anilines.",
+    limitations="Fails with electron-poor arenes. Free phenols can give Duff or Reimer-Tiemann products.",
+    mechanism="POCl₃ + DMF → chloroiminium salt (Vilsmeier reagent) → electrophilic substitution at electron-rich C → iminium → hydrolysis → aldehyde.",
+    refs="Vilsmeier, Haack, Ber. 1927, 60, 119.",
+    related="Gattermann, Duff, Reimer-Tiemann",
+    functional_groups="arene, aldehyde, DMF")
+
+_nr("Weinreb Amide",
+    aliases=["Weinreb amide", "Weinreb ketone synthesis"],
+    category="C-C Bond Formation", type_="Ketone Synthesis",
+    summary="N-Methoxy-N-methylamides (Weinreb amides) react with Grignard/organolithium → ketones (no over-addition).",
+    conditions="R-C(=O)N(OMe)Me + R'MgBr (or R'Li), THF, –78 °C → 0 °C. Single equivalent of nucleophile.",
+    substrate="Weinreb amides + RMgBr → ketones. Also: + DIBAL → aldehydes.",
+    limitations="Requires Weinreb amide preparation (extra step). Sensitive to steric hindrance.",
+    mechanism="Nucleophile attacks C=O → tetrahedral intermediate chelated by N-OMe → stable → does not collapse until workup → ketone.",
+    refs="Nahm, Weinreb, Tetrahedron Lett. 1981, 22, 3815.",
+    related="Grignard + acid chloride, Fukuyama coupling",
+    functional_groups="amide, Grignard, ketone, aldehyde")
+
+_nr("Wharton Fragmentation",
+    aliases=["Wharton reaction", "Wharton transposition"],
+    category="Rearrangement", type_="Transposition",
+    summary="α,β-Epoxyketones + hydrazine → allylic alcohols via [2,3]-sigmatropic shift.",
+    conditions="α,β-Epoxyketone + H₂NNH₂·H₂O, EtOH/AcOH, reflux.",
+    substrate="α,β-Epoxyketones → allylic alcohols (transposition of C=O).",
+    limitations="Requires α,β-epoxy ketone substrate specifically.",
+    mechanism="Hydrazone forms → [2,3]-sigmatropic shift → diazene intermediate → loss of N₂ → allylic alcohol.",
+    refs="Wharton, Bohlen, J. Org. Chem. 1961, 26, 3615.",
+    related="Bamford-Stevens, Shapiro",
+    functional_groups="epoxide, ketone, allylic alcohol")
+
+_nr("Wittig Reaction",
+    aliases=["Wittig reaction", "Wittig olefination"],
+    category="C-C Bond Formation", type_="Olefination",
+    summary="Phosphonium ylide + aldehyde/ketone → alkene + Ph₃P=O.",
+    conditions="Ph₃P=CHR (ylide from Ph₃P⁺CH₂R X⁻ + base) + RCHO, THF, –78 °C → rt. Non-stabilized → Z, stabilized → E.",
+    substrate="Aldehydes + ylides → alkenes. Non-stabilized (R = alkyl) → cis. Stabilized (R = CO₂R, CN) → trans.",
+    limitations="Triphenylphosphine oxide removal. Z/E selectivity depends on ylide type.",
+    mechanism="Ylide + aldehyde → betaine → oxaphosphetane (via [2+2] or stepwise) → retro-[2+2] → alkene + Ph₃P=O.",
+    refs="Wittig, Geissler, Annalen 1953, 580, 44.",
+    related="HWE, Still-Gennari, Julia, Tebbe",
+    functional_groups="aldehyde, ylide, alkene")
+
+_nr("Wolff Rearrangement",
+    aliases=["Wolff rearrangement", "Arndt-Eistert (Wolff step)"],
+    category="Rearrangement", type_="Carbene Rearrangement",
+    summary="α-Diazo ketones → ketenes via Wolff rearrangement (loss of N₂, [1,2]-shift).",
+    conditions="α-Diazoketone + hν or Ag₂O or heat → ketene → trap with H₂O, ROH, or amine.",
+    substrate="Acyl chloride + CH₂N₂ → α-diazoketone → ketene → acid, ester, or amide (one carbon homologation).",
+    limitations="Diazoketone hazards. Wolff competes with C-H insertion (Rh catalysis).",
+    mechanism="α-Diazoketone → loss of N₂ → carbene/carbenoid → [1,2]-shift → ketene → nucleophilic trapping.",
+    refs="Wolff, Annalen 1912, 394, 23.",
+    related="Arndt-Eistert, Curtius",
+    functional_groups="diazo, ketene, carboxylic acid")
+
+_nr("Yamaguchi Esterification",
+    aliases=["Yamaguchi esterification", "Yamaguchi macrolactonization"],
+    category="Functional Group Interconversion", type_="Esterification/Macrolactonization",
+    summary="2,4,6-Trichlorobenzoyl chloride-mediated esterification, especially for macrolactonization.",
+    conditions="RCO₂H + 2,4,6-Cl₃C₆H₂COCl, Et₃N, THF → mixed anhydride → add ROH + DMAP → ester. Macrolactonization: high dilution.",
+    substrate="Seco-acids → macrolactones (12–20-membered). Also intermolecular esterification of hindered alcohols.",
+    limitations="High dilution for macrolactonization. Expensive reagent. DMAP crucial for rate.",
+    mechanism="Acid + trichlorobenzoyl chloride → mixed anhydride → DMAP-catalyzed aminolysis → acyl-DMAP → alcoholysis → ester.",
+    refs="Inanaga, Hirata, Saeki, Katsuki, Yamaguchi, Bull. Chem. Soc. Jpn. 1979, 52, 1989.",
+    related="Steglich, Fischer, Mitsunobu, Shiina",
+    functional_groups="carboxylic acid, alcohol, ester, macrolactone")
+
+_nr("Zincke Aldehyde",
+    aliases=["Zincke aldehyde", "Zincke reaction"],
+    category="Heterocycle Formation", type_="Ring Opening/Closing",
+    summary="Pyridinium salts (Zincke salts) react with primary amines → N-substituted pyridinium salts (pyridine N-exchange).",
+    conditions="Pyridine + 2,4-dinitro-chlorobenzene → Zincke salt → R-NH₂ → N-substituted pyridinium → base → Zincke aldehyde (5-amino-2,4-pentadienal).",
+    substrate="Pyridinium salts + 1° amines → pyridinium exchange. Ring-opened intermediates = Zincke aldehydes.",
+    limitations="Requires DNB activation. Multi-step. Low yields for electron-poor amines.",
+    mechanism="Ring opens via retro-electrocyclic → pentadienal-iminium (Zincke aldehyde) → new amine condenses → ring closes → new pyridinium.",
+    refs="Zincke, Annalen 1903, 330, 361.",
+    related="Chichibabin",
+    functional_groups="pyridine, amine")
+
+_nr("Biginelli Reaction",
+    aliases=["Biginelli reaction", "Biginelli 3CR"],
+    category="Heterocycle Formation", type_="Multicomponent",
+    summary="Three-component synthesis of dihydropyrimidinones (DHPMs) from aldehyde + urea + β-ketoester.",
+    conditions="RCHO + urea + β-ketoester, HCl or Lewis acid (Yb(OTf)₃, FeCl₃), EtOH, reflux.",
+    substrate="Aldehydes + urea + 1,3-dicarbonyls → 3,4-dihydropyrimidin-2(1H)-ones. Enantioselective with chiral phosphoric acid.",
+    limitations="Moderate yields with aliphatic aldehydes. Slow with bulky substrates.",
+    mechanism="Aldehyde + urea → N-acyliminium → β-ketoester → Mannich-type → cyclization → DHPM.",
+    refs="Biginelli, Ber. 1891, 24, 1317.",
+    related="Hantzsch, Ugi, Passerini",
+    functional_groups="aldehyde, urea, β-ketoester, dihydropyrimidinone")
+
+_nr("Corey-Bakshi-Shibata Reduction",
+    aliases=["CBS reduction", "Corey-Bakshi-Shibata"],
+    category="Reduction", type_="Asymmetric Reduction",
+    summary="Oxazaborolidine-catalyzed asymmetric reduction of prochiral ketones with BH₃.",
+    conditions="Ketone + BH₃·THF (or catecholborane), CBS catalyst (10 mol%), toluene, –20 °C to rt.",
+    substrate="Prochiral ketones → chiral secondary alcohols with >95% ee. Aryl-alkyl ketones best.",
+    limitations="Both enantiomers of catalyst needed for R/S. Bulky ketones slow. Enones can give 1,4.",
+    mechanism="CBS oxazaborolidine coordinates BH₃ → B-H delivered to activated ketone → 6-membered TS → enantioselective hydride transfer.",
+    refs="Corey, Bakshi, Shibata, JACS 1987, 109, 5551.",
+    related="Noyori, Alpine-Borane, Midland, Luche",
+    functional_groups="ketone, alcohol, chiral")
+
+_nr("Shiina Macrolactonization",
+    aliases=["Shiina macrolactonization", "Shiina esterification"],
+    category="Functional Group Interconversion", type_="Macrolactonization",
+    summary="MNBA (2-methyl-6-nitrobenzoic anhydride)-mediated macrolactonization, milder than Yamaguchi.",
+    conditions="Seco-acid + MNBA, DMAP (cat.), Et₃N, CH₂Cl₂, high dilution (0.002 M), rt.",
+    substrate="ω-Hydroxy acids → macrolactones (often with better yields than Yamaguchi for acid-sensitive substrates).",
+    limitations="High dilution essential. MNBA must be freshly prepared.",
+    mechanism="Seco-acid + MNBA → mixed anhydride → DMAP activation → intramolecular cyclization → macrolactone.",
+    refs="Shiina, Kubota, Oshiumi, Hashizume, J. Org. Chem. 2004, 69, 1822.",
+    related="Yamaguchi, Mitsunobu, Corey-Nicolaou",
+    functional_groups="carboxylic acid, alcohol, macrolactone")
+
+_nr("Suzuki-Miyaura Coupling",
+    aliases=["Suzuki-Miyaura"],
+    category="C-C Bond Formation", type_="Cross-Coupling",
+    summary="Pd-catalyzed coupling of organoboron compounds with organic halides — the most widely used cross-coupling.",
+    conditions="ArX + ArB(OH)₂, Pd(PPh₃)₄ or Pd(dppf)Cl₂, K₂CO₃ or K₃PO₄, dioxane/H₂O, 80 °C. Also: SPhos, XPhos ligands for challenging substrates.",
+    substrate="Aryl/vinyl boronic acids/esters + aryl/vinyl halides/triflates → biaryls, dienes. Also alkyl-B (sp3-sp2).",
+    limitations="Aryl chlorides need bulky ligands (SPhos). Boronic acid protodeborylation. Base required.",
+    mechanism="Pd(0) + ArX → oxidative addition → Pd(II) + base → transmetalation with ArB(OH)₂ → reductive elimination → Ar-Ar + Pd(0).",
+    refs="Miyaura, Suzuki, Chem. Rev. 1995, 95, 2457. Nobel Prize 2010.",
+    related="Heck, Negishi, Stille, Kumada, Hiyama",
+    functional_groups="aryl halide, boronic acid, biaryl")
+
+_nr("Trost Asymmetric Allylic Alkylation",
+    aliases=["Trost AAA", "asymmetric allylic alkylation"],
+    category="C-C Bond Formation", type_="Asymmetric Allylation",
+    summary="Pd-catalyzed AAA with Trost's DACH-phenyl ligand for enantioselective allylation.",
+    conditions="Allyl acetate/carbonate + nucleophile (malonate, amine, phenol), Pd₂(dba)₃, Trost ligand, CH₂Cl₂, rt.",
+    substrate="Allyl substrates + soft nucleophiles → branched/linear products with >90% ee.",
+    limitations="Hard nucleophiles give poor ee. Linear/branched selectivity can be challenging.",
+    mechanism="Pd(0) → oxidative addition → π-allyl-Pd(II) → chiral environment from Trost ligand → nucleophilic attack from differentiated face → product.",
+    refs="Trost, Van Vranken, Chem. Rev. 1996, 96, 395.",
+    related="Tsuji-Trost, Pd-allyl chemistry",
+    functional_groups="allyl acetate, malonate, amine")
+
+_nr("Swern Oxidation",
+    aliases=["Swern oxidation"],
+    category="Oxidation", type_="Alcohol Oxidation",
+    summary="DMSO/oxalyl chloride-mediated oxidation of primary/secondary alcohols to aldehydes/ketones.",
+    conditions="(COCl)₂, DMSO, CH₂Cl₂, –78 °C → add ROH → Et₃N → warm to rt.",
+    substrate="1° alcohols → aldehydes (no over-oxidation). 2° alcohols → ketones. Very mild and selective.",
+    limitations="Must maintain –78 °C during activation. Generates Me₂S (foul smell). Excess Et₃N needed.",
+    mechanism="DMSO + (COCl)₂ → chlorosulfonium → ROH attacks S → alkoxysulfonium → Et₃N → intramolecular elimination → C=O.",
+    refs="Omura, Swern, Tetrahedron 1978, 34, 1651.",
+    related="Dess-Martin, PCC, TEMPO, Parikh-Doering",
+    functional_groups="alcohol, aldehyde, ketone")
+
+_nr("Barton-McCombie Deoxygenation",
+    aliases=["Barton-McCombie", "radical deoxygenation"],
+    category="Radical", type_="Deoxygenation",
+    summary="Radical-mediated removal of OH groups: alcohol → xanthate/thiocarbamate → radical reduction → deoxygenated product.",
+    conditions="ROH → xanthate (NaH, CS₂, MeI) → Bu₃SnH, AIBN, toluene, reflux. Modern: (TMS)₃SiH replaces tin.",
+    substrate="Secondary and tertiary alcohols → deoxygenated. Tolerates many functional groups.",
+    limitations="Tin waste (toxic). Xanthate preparation adds step. Primary alcohols less efficient.",
+    mechanism="Bu₃Sn• abstracts S from xanthate → radical on carbon → β-scission → C radical → H from Bu₃SnH → product + new Bu₃Sn•.",
+    refs="Barton, McCombie, J. Chem. Soc., Perkin Trans. 1 1975, 1574.",
+    related="Barton decarboxylation",
+    functional_groups="alcohol, xanthate, radical")
+
+_nr("Corey-Winter Olefin Synthesis",
+    aliases=["Corey-Winter"],
+    category="C-C Bond Formation", type_="Olefination",
+    summary="1,2-Diols → cyclic thionocarbonate → treatment with P(OMe)₃ → alkene (syn-elimination).",
+    conditions="Diol + thiophosgene or thiocarbonyldiimidazole → cyclic thionocarbonate → P(OMe)₃, heat → alkene.",
+    substrate="1,2-Diols → alkenes stereospecifically (syn-elimination: threo → Z, erythro → E).",
+    limitations="Multi-step. Thiophosgene toxic. Better reagents (TCDI) available.",
+    mechanism="P(OMe)₃ attacks S → betaine → cheletropic extrusion of CO/S → alkene (suprafacial, syn-periplanar).",
+    refs="Corey, Winter, JACS 1963, 85, 2677.",
+    related="Ramberg-Bäcklund, Bamford-Stevens",
+    functional_groups="diol, alkene, thionocarbonate")
+
+_nr("Mitsunobu Reaction",
+    aliases=["Mitsunobu reaction"],
+    category="Substitution", type_="Inversion SN2",
+    summary="DIAD/PPh₃-mediated substitution of alcohols with inversion of stereochemistry.",
+    conditions="ROH + NuH + DIAD (or DEAD) + PPh₃, THF, 0 °C → rt. Nu = carboxylates, phenols, phthalimides, sulfonamides, azides.",
+    substrate="2° alcohols → substituted with inversion. Converts ROH → esters, ethers, azides, amines (Gabriel).",
+    limitations="Atom-poor (2 eq reagents generate stoichiometric Ph₃P=O + DIAD-H₂). Purification of byproducts difficult.",
+    mechanism="DIAD + PPh₃ → betaine → protonation by NuH → ion pair → SN2 on activated alcohol → product with inversion.",
+    refs="Mitsunobu, Yamada, Bull. Chem. Soc. Jpn. 1967, 40, 2380.",
+    related="Appel, Williamson, Gabriel",
+    functional_groups="alcohol, ester, ether, inversion")
+
+_nr("Grubbs Metathesis",
+    aliases=["cross metathesis", "CM", "olefin cross metathesis"],
+    category="C-C Bond Formation", type_="Metathesis",
+    summary="Ru-catalyzed olefin cross-metathesis for convergent C=C bond formation between two alkenes.",
+    conditions="Alkene A + alkene B, Grubbs II or Hoveyda-Grubbs, CH₂Cl₂, 40 °C. Ethylene removed (N₂ sparge).",
+    substrate="Terminal alkenes + acrylates, styrenes, or allyl systems → cross products. Type I/II/III selectivity rules.",
+    limitations="Homodimerization competes. Catalyst type-selectivity must be matched. Electron-rich olefins are Type I.",
+    mechanism="Ru=CHR initiates → [2+2] cycloaddition → metallacyclobutane → retro-[2+2] → new Ru=CHR' → repeat → statistical/cross product.",
+    refs="Chatterjee, Choi, Sanders, Grubbs, JACS 2003, 125, 11360.",
+    related="RCM, ROMP, Olefin Metathesis",
+    functional_groups="alkene, acrylate, styrene")
+
+_nr("Oppolzer Sultam",
+    aliases=["Oppolzer auxiliary", "camphorsultam auxiliary"],
+    category="C-C Bond Formation", type_="Asymmetric Alkylation",
+    summary="Bornane-10,2-sultam (Oppolzer's camphorsultam) as chiral auxiliary for asymmetric Diels-Alder, aldol, and alkylation.",
+    conditions="N-Acylsultam + LDA → enolate → electrophile (alkyl halide, aldehyde, dienophile) → auxiliary removal (LiOH/H₂O₂).",
+    substrate="Diels-Alder: dienophile on sultam → endo adduct with >98% de. Aldol: syn-selective.",
+    limitations="Stoichiometric chiral auxiliary. Multi-step attachment/removal.",
+    mechanism="Enolate chelated by SO₂ → electrophile approaches from less-hindered exo face → high de. Li or Ti enolates.",
+    refs="Oppolzer, Tetrahedron 1987, 43, 1969.",
+    related="Evans, Myers, Enders",
+    functional_groups="acryloyl, aldehyde, Diels-Alder, sultam")
+
+# =============================================================================
+# Lookup Functions
+# =============================================================================
+
+
+def lookup_reaction(query: str) -> list[dict]:
+    """Search named reactions by name, category, type, or substrate keyword."""
+    q = query.lower().strip()
+    results = []
+    seen = set()
+    # Exact match first
+    if q in NAMED_REACTIONS:
+        r = NAMED_REACTIONS[q]
+        if r["name"] not in seen:
+            results.append(r)
+            seen.add(r["name"])
+
+    # Fuzzy match: search across all fields
+    for key, r in NAMED_REACTIONS.items():
+        if r["name"] in seen:
+            continue
+        searchable = " ".join([
+            r["name"], " ".join(r["aliases"]), r["category"], r["type"],
+            r["summary"], r["conditions"], r["substrate"], r["functional_groups"],
+        ]).lower()
+        if q in searchable:
+            results.append(r)
+            seen.add(r["name"])
+
+    return results[:15]
+
+
+# =============================================================================
+# Protecting Groups Database
+# =============================================================================
+
+# Stability scale: "S" = stable, "M" = moderately stable, "L" = labile
+# Conditions: acid, base, nuc (nucleophile), ox (oxidation), red (reduction), h2_pd (hydrogenolysis)
+
+PROTECTING_GROUPS: dict[str, list[dict]] = {
+    "hydroxyl": [
+        {"name": "TMS", "full_name": "Trimethylsilyl ether", "protection": "TMSCl, imidazole or Et3N, DMF or CH2Cl2", "deprotection": "TBAF, HF·py, AcOH/H2O/THF, or K2CO3/MeOH", "stability": {"acid": "L", "base": "M", "nuc": "M", "ox": "S", "red": "S", "h2_pd": "S"}, "notes": "Least stable silyl ether. Removed under mildly acidic conditions."},
+        {"name": "TBS (TBDMS)", "full_name": "tert-Butyldimethylsilyl ether", "protection": "TBSCl, imidazole, DMF (or TBSOTf, 2,6-lutidine, CH2Cl2)", "deprotection": "TBAF/THF, HF·py, AcOH/H2O, p-TsOH/MeOH", "stability": {"acid": "M", "base": "S", "nuc": "S", "ox": "S", "red": "S", "h2_pd": "S"}, "notes": "Most popular silyl ether. ~10⁴× more stable than TMS. 1° OH selectivity over 2° with TBSCl/imid."},
+        {"name": "TIPS", "full_name": "Triisopropylsilyl ether", "protection": "TIPSCl, imidazole, DMF or TIPSOTf, 2,6-lutidine", "deprotection": "TBAF, HF·py (slower than TBS)", "stability": {"acid": "S", "base": "S", "nuc": "S", "ox": "S", "red": "S", "h2_pd": "S"}, "notes": "Very stable silyl ether. Steric bulk provides acid stability. ~10²× more stable than TBS toward acid."},
+        {"name": "TES", "full_name": "Triethylsilyl ether", "protection": "TESCl, imidazole, DMF", "deprotection": "TBAF, AcOH, PPTS", "stability": {"acid": "L", "base": "S", "nuc": "M", "ox": "S", "red": "S", "h2_pd": "S"}, "notes": "Intermediate stability. More stable than TMS, less than TBS."},
+        {"name": "TBDPS", "full_name": "tert-Butyldiphenylsilyl ether", "protection": "TBDPSCl, imidazole, DMF", "deprotection": "TBAF (slow, sometimes requires heat), HF·py", "stability": {"acid": "S", "base": "S", "nuc": "S", "ox": "S", "red": "S", "h2_pd": "S"}, "notes": "Very stable. UV-active (diphenyl). Selective for 1° OH. Compatible with many reaction conditions."},
+        {"name": "Bn (Benzyl)", "full_name": "Benzyl ether", "protection": "BnBr, NaH, DMF or THF; or BnOC(=NH)CCl3, TfOH (Dudley)", "deprotection": "H2, Pd/C (hydrogenolysis); DDQ (PMB-selective); Li, NH3(l)", "stability": {"acid": "S", "base": "S", "nuc": "S", "ox": "M", "red": "M", "h2_pd": "L"}, "notes": "Removed by hydrogenolysis. Orthogonal to silyl ethers. Very stable to acid/base."},
+        {"name": "PMB", "full_name": "p-Methoxybenzyl ether", "protection": "PMBCl, NaH, DMF; or PMBTCA, BF3·Et2O", "deprotection": "DDQ, CH2Cl2/H2O; CAN; TFA; H2, Pd/C", "stability": {"acid": "M", "base": "S", "nuc": "S", "ox": "L", "red": "M", "h2_pd": "L"}, "notes": "Oxidatively labile (DDQ removes selectively in presence of Bn). More acid-labile than Bn."},
+        {"name": "Ac (Acetyl)", "full_name": "Acetyl ester", "protection": "Ac2O, pyridine or DMAP; AcCl, Et3N", "deprotection": "K2CO3/MeOH (Zemplén); LiOH/THF-H2O; NaOMe/MeOH; NH3/MeOH", "stability": {"acid": "S", "base": "L", "nuc": "L", "ox": "S", "red": "S", "h2_pd": "S"}, "notes": "Removed by mild base (transesterification in MeOH). Cheap, easy. Not stable to Grignard, LAH, or basic conditions."},
+        {"name": "Piv (Pivaloyl)", "full_name": "Pivaloyl ester", "protection": "PivCl, Et3N, DMAP", "deprotection": "DIBAL-H, -78°C; LiAlH4; KOH(aq)", "stability": {"acid": "S", "base": "M", "nuc": "M", "ox": "S", "red": "M", "h2_pd": "S"}, "notes": "Sterically hindered ester. More resistant to base than Ac. Selective removal with DIBAL."},
+        {"name": "MOM", "full_name": "Methoxymethyl ether", "protection": "MOMCl, iPr2NEt, CH2Cl2 (carcinogen caution); or dimethoxymethane, P2O5", "deprotection": "HCl/MeOH; conc. HCl/THF; PPTS/MeOH or iPrOH/heat; TMSBr", "stability": {"acid": "L", "base": "S", "nuc": "S", "ox": "S", "red": "S", "h2_pd": "S"}, "notes": "Acid-labile acetal. MOMCl is a suspected carcinogen — handle with care. Stable to base, nucleophiles, organometallics."},
+        {"name": "THP", "full_name": "Tetrahydropyranyl ether", "protection": "DHP (3,4-dihydro-2H-pyran), PPTS or TsOH, CH2Cl2", "deprotection": "PPTS/MeOH or EtOH; dilute HCl; AcOH/H2O/THF", "stability": {"acid": "L", "base": "S", "nuc": "S", "ox": "S", "red": "S", "h2_pd": "S"}, "notes": "Acid-labile acetal. Creates new stereocenter (diastereomers). Cheap, easy to install. Can complicate NMR."},
+        {"name": "Allyl", "full_name": "Allyl ether", "protection": "AllBr, NaH, DMF", "deprotection": "Pd(PPh3)4, morpholine or PhSiH3/Pd(PPh3)4; or Ir catalyst/H2 then acid", "stability": {"acid": "S", "base": "S", "nuc": "S", "ox": "M", "red": "M", "h2_pd": "M"}, "notes": "Removed by Pd(0)-catalyzed allyl transfer. Orthogonal to acid/base-labile groups."},
+    ],
+    "amino": [
+        {"name": "Boc", "full_name": "tert-Butyloxycarbonyl", "protection": "Boc2O, NaOH or Et3N or DMAP, THF/H2O", "deprotection": "TFA/CH2Cl2 (25-50%); 4M HCl in dioxane; TMSOTf/2,6-lutidine", "stability": {"acid": "L", "base": "S", "nuc": "S", "ox": "S", "red": "S", "h2_pd": "S"}, "notes": "Acid-labile. Orthogonal to Fmoc (base-labile). Most common amino PG along with Fmoc and Cbz. Stable to hydrogenolysis, base, nucleophiles."},
+        {"name": "Fmoc", "full_name": "9-Fluorenylmethyloxycarbonyl", "protection": "Fmoc-Cl or Fmoc-OSu, Na2CO3, dioxane/H2O", "deprotection": "Piperidine/DMF (20%); DBU; Et2NH", "stability": {"acid": "S", "base": "L", "nuc": "L", "ox": "S", "red": "S", "h2_pd": "S"}, "notes": "Base-labile. Orthogonal to Boc. Standard in SPPS (solid-phase peptide synthesis). UV-active (monitoring deprotection)."},
+        {"name": "Cbz (Z)", "full_name": "Benzyloxycarbonyl", "protection": "CbzCl (benzyl chloroformate), NaOH or NaHCO3, H2O/dioxane", "deprotection": "H2, Pd/C; HBr/AcOH; TMSI", "stability": {"acid": "M", "base": "S", "nuc": "S", "ox": "M", "red": "M", "h2_pd": "L"}, "notes": "Removed by hydrogenolysis. Orthogonal to Boc. Stable to mild acid and base."},
+        {"name": "Alloc", "full_name": "Allyloxycarbonyl", "protection": "Alloc-Cl, pyridine", "deprotection": "Pd(PPh3)4, PhSiH3 or morpholine", "stability": {"acid": "S", "base": "S", "nuc": "S", "ox": "S", "red": "M", "h2_pd": "M"}, "notes": "Removed by Pd(0). Orthogonal to both Boc and Fmoc. Used in complex peptide synthesis."},
+        {"name": "Ns (Nosyl)", "full_name": "2-Nitrobenzenesulfonyl", "protection": "NsCl, Et3N, CH2Cl2", "deprotection": "PhSH, K2CO3, DMF; or mercaptoacetic acid", "stability": {"acid": "S", "base": "S", "nuc": "L", "ox": "S", "red": "M", "h2_pd": "M"}, "notes": "Removed by thiolysis (Fukuyama conditions). Activates nitrogen for alkylation (Mitsunobu on sulfonamide N)."},
+        {"name": "Ts (Tosyl)", "full_name": "p-Toluenesulfonyl", "protection": "TsCl, pyridine or Et3N", "deprotection": "Na/naphthalenide; Mg/MeOH; SmI2; HBr/AcOH (harsh)", "stability": {"acid": "S", "base": "S", "nuc": "S", "ox": "S", "red": "M", "h2_pd": "S"}, "notes": "Very stable — difficult to remove. Often considered semi-permanent. Electron-withdrawing on N."},
+        {"name": "Troc", "full_name": "2,2,2-Trichloroethoxycarbonyl", "protection": "TrocCl, pyridine", "deprotection": "Zn, AcOH; Cd/Pb couple", "stability": {"acid": "S", "base": "S", "nuc": "S", "ox": "S", "red": "L", "h2_pd": "S"}, "notes": "Removed reductively (Zn). Orthogonal to Boc, Fmoc, Cbz. Used in carbohydrate chemistry."},
+        {"name": "Bn (N-Benzyl)", "full_name": "N-Benzyl", "protection": "BnBr, K2CO3, DMF; or reductive amination with PhCHO/NaBH4", "deprotection": "H2, Pd/C; Birch reduction; CAN (for PMP)", "stability": {"acid": "S", "base": "S", "nuc": "S", "ox": "M", "red": "S", "h2_pd": "L"}, "notes": "Removed by hydrogenolysis. Simple and robust. N-PMB variant removed by CAN or DDQ."},
+    ],
+    "carbonyl": [
+        {"name": "1,3-Dioxolane", "full_name": "Ethylene acetal/ketal", "protection": "HOCH2CH2OH, p-TsOH, toluene, Dean-Stark; or (MeO)2CH2, TMSOTf", "deprotection": "Aqueous acid (HCl, p-TsOH, Amberlyst); acetone/H+; I2/acetone", "stability": {"acid": "L", "base": "S", "nuc": "S", "ox": "S", "red": "S", "h2_pd": "S"}, "notes": "Standard carbonyl protection. Stable to base, nucleophiles, metal hydrides (NaBH4, LiAlH4), Grignard, organolithium."},
+        {"name": "1,3-Dioxane", "full_name": "Propylene acetal/ketal", "protection": "HOCH2CH2CH2OH, p-TsOH, toluene, Dean-Stark", "deprotection": "Aqueous acid", "stability": {"acid": "L", "base": "S", "nuc": "S", "ox": "S", "red": "S", "h2_pd": "S"}, "notes": "Slightly more stable than 1,3-dioxolane. 6-membered ring."},
+        {"name": "Dithiane", "full_name": "1,3-Dithiane (thioacetal)", "protection": "HSCH2CH2CH2SH, BF3·Et2O or I2; or HSCH2CH2SH for dithiolane", "deprotection": "HgCl2/CaCO3; NBS; MeI then hydrolysis; Selectfluor", "stability": {"acid": "S", "base": "S", "nuc": "S", "ox": "L", "red": "S", "h2_pd": "S"}, "notes": "Acid-stable unlike O-acetals. Also umpolung synthon (dithiane anion = acyl anion equivalent). Hg or oxidative deprotection."},
+        {"name": "Dimethyl acetal", "full_name": "Dimethyl acetal", "protection": "MeOH, p-TsOH or trimethyl orthoformate, p-TsOH", "deprotection": "Aqueous acid, acetone/p-TsOH", "stability": {"acid": "L", "base": "S", "nuc": "S", "ox": "S", "red": "S", "h2_pd": "S"}, "notes": "Open-chain acetal. Slightly more acid-labile than cyclic acetals."},
+    ],
+    "carboxyl": [
+        {"name": "Methyl ester", "full_name": "Methyl ester", "protection": "CH2N2 (diazomethane); MeOH/H+; MeI/K2CO3", "deprotection": "LiOH/THF-H2O; NaOH; Me3SnOH; BBr3 (for phenyl methyl ethers too)", "stability": {"acid": "S", "base": "L", "nuc": "L", "ox": "S", "red": "M", "h2_pd": "S"}, "notes": "Simplest ester PG. Removed by saponification. Stable to acid. Not stable to strong nucleophiles or base."},
+        {"name": "Ethyl ester", "full_name": "Ethyl ester", "protection": "EtOH/H+; EtI, K2CO3", "deprotection": "LiOH/THF-H2O; NaOH; KOH", "stability": {"acid": "S", "base": "L", "nuc": "L", "ox": "S", "red": "M", "h2_pd": "S"}, "notes": "Similar to methyl ester. Slightly slower saponification."},
+        {"name": "tert-Butyl ester", "full_name": "tert-Butyl ester", "protection": "Isobutylene, H2SO4; Boc2O, DMAP (for amino acids); tBuOH, DCC", "deprotection": "TFA; 4M HCl/dioxane; TMSOTf/2,6-lutidine", "stability": {"acid": "L", "base": "S", "nuc": "S", "ox": "S", "red": "S", "h2_pd": "S"}, "notes": "Acid-labile (like Boc). Stable to base and nucleophiles. Cleaved under same conditions as Boc."},
+        {"name": "Benzyl ester", "full_name": "Benzyl ester", "protection": "BnBr, K2CO3, DMF; BnOH, DCC, DMAP; PhCH2OH, H+", "deprotection": "H2, Pd/C; HBr/AcOH; TMSI", "stability": {"acid": "M", "base": "M", "nuc": "M", "ox": "M", "red": "M", "h2_pd": "L"}, "notes": "Removed by hydrogenolysis. Orthogonal to tBu ester."},
+        {"name": "Allyl ester", "full_name": "Allyl ester", "protection": "AllBr, K2CO3; allyl alcohol, DCC", "deprotection": "Pd(PPh3)4, morpholine or PhSiH3", "stability": {"acid": "S", "base": "M", "nuc": "M", "ox": "S", "red": "M", "h2_pd": "M"}, "notes": "Removed by Pd(0)-catalyzed allyl transfer. Orthogonal to Boc and Fmoc."},
+        {"name": "TMSE", "full_name": "2-(Trimethylsilyl)ethyl ester", "protection": "TMSCH2CH2OH, DCC, DMAP", "deprotection": "TBAF, THF", "stability": {"acid": "M", "base": "S", "nuc": "S", "ox": "S", "red": "S", "h2_pd": "S"}, "notes": "Removed by fluoride (β-elimination of TMS). Very stable to base."},
+    ],
+}
+
+
+def lookup_pg(query: str, functional_group: str | None = None) -> list[dict]:
+    """Search protecting groups by name, functional group, or condition."""
+    q = query.lower().strip()
+    results = []
+
+    groups_to_search = {}
+    if functional_group:
+        fg = functional_group.lower().strip()
+        if fg in PROTECTING_GROUPS:
+            groups_to_search[fg] = PROTECTING_GROUPS[fg]
+    else:
+        groups_to_search = PROTECTING_GROUPS
+
+    for fg_name, pgs in groups_to_search.items():
+        for pg in pgs:
+            searchable = " ".join([
+                pg["name"], pg.get("full_name", ""), pg.get("protection", ""),
+                pg.get("deprotection", ""), pg.get("notes", ""),
+            ]).lower()
+            if q in searchable or q in pg["name"].lower():
+                results.append({"functional_group": fg_name, **pg})
+
+    return results
+
+
+# =============================================================================
+# Workup Procedures
+# =============================================================================
+
+WORKUP_PROCEDURES: dict[str, dict] = {
+    "standard_aqueous": {
+        "name": "Standard Aqueous Workup",
+        "when": "Most reactions in organic solvents (CH2Cl2, EtOAc, Et2O, toluene)",
+        "steps": [
+            "Dilute reaction with organic solvent (EtOAc or CH2Cl2)",
+            "Transfer to separatory funnel",
+            "Wash with water (1×), then sat. NaHCO3 (1×) to remove acids",
+            "Wash with brine (1×) to break emulsions and dry organic layer",
+            "Dry organic layer over Na2SO4 or MgSO4 (15-30 min)",
+            "Filter off drying agent",
+            "Concentrate under reduced pressure (rotovap, water bath ≤40°C)",
+        ],
+        "tips": "Add brine if emulsion forms. If product is water-soluble, use back-extraction with organic solvent (3×). Check pH of aqueous layers.",
+    },
+    "acid_base_extraction": {
+        "name": "Acid-Base Extraction",
+        "when": "Separating acids, bases, and neutrals in a mixture",
+        "steps": [
+            "Dissolve mixture in Et2O or CH2Cl2",
+            "Extract with 1M HCl (2×) — removes basic compounds (amines) into aqueous layer",
+            "Extract organic layer with 1M NaOH (2×) — removes acidic compounds (carboxylic acids, phenols) into aqueous layer",
+            "Remaining organic layer contains neutral compounds — dry over Na2SO4, filter, concentrate",
+            "To recover bases: basify HCl extract with NaOH → extract with organic solvent",
+            "To recover acids: acidify NaOH extract with HCl → extract with organic solvent",
+        ],
+        "tips": "For phenols vs carboxylic acids: extract first with NaHCO3 (removes only acids), then NaOH (removes phenols).",
+    },
+    "fieser_workup_lah": {
+        "name": "Fieser Workup (LiAlH4 Reduction)",
+        "when": "After LiAlH4 (LAH) reductions — quenching the aluminum salts",
+        "steps": [
+            "Cool reaction to 0°C",
+            "For n grams of LAH used, add SLOWLY and DROPWISE:",
+            "  n mL water (CAUTION: H2 evolution! Exothermic!)",
+            "  n mL 15% NaOH(aq)",
+            "  3n mL water",
+            "Stir vigorously until white granular precipitate forms (30-60 min)",
+            "Filter through Celite, wash filter cake with Et2O or EtOAc",
+            "Dry filtrate over Na2SO4, filter, concentrate",
+        ],
+        "tips": "If precipitate is gelatinous instead of granular, add more NaOH. Alternatively, use Rochelle's salt (sat. sodium potassium tartrate) workup: quench into cold sat. Rochelle's salt, stir until layers separate. Na2SO4·10H2O method also works for small scale.",
+    },
+    "fieser_workup_dibal": {
+        "name": "Workup for DIBAL-H Reductions",
+        "when": "After DIBAL-H reductions (ester → aldehyde, etc.)",
+        "steps": [
+            "Cool to -78°C (or 0°C)",
+            "Quench with sat. Rochelle's salt (sodium potassium tartrate) solution",
+            "Warm to RT and stir vigorously for 1-2 hours until layers separate clearly",
+            "Separate layers, extract aqueous with organic solvent (2-3×)",
+            "Dry organic layer, filter, concentrate",
+        ],
+        "tips": "Alternative: quench with MeOH at -78°C, then add sat. Rochelle's salt. Celite filtration of aluminum salts if cloudy. Na/K tartrate chelates aluminum → clear phase separation.",
+    },
+    "oxidative_workup": {
+        "name": "Peroxide/Oxidant Quench (After Hydroboration etc.)",
+        "when": "After reactions using boranes, peroxides, or other oxidants",
+        "steps": [
+            "If using H2O2: ensure all peroxide is decomposed before workup",
+            "Quench excess borane with careful addition of MeOH or water (gas evolution!)",
+            "For hydroboration-oxidation: NaOH/H2O2 step then standard aqueous workup",
+            "Test for peroxides with starch-iodide paper before concentrating",
+            "Never concentrate to dryness when peroxides might be present!",
+        ],
+        "tips": "Na2SO3 or Na2S2O3 quenches excess peroxide/peracid. Always test before evaporation. Ethereal solvents can form peroxides.",
+    },
+    "metal_removal": {
+        "name": "Transition Metal Removal",
+        "when": "After Pd, Ru, Cu, or other transition metal-catalyzed reactions",
+        "steps": [
+            "For Pd: filter through Celite pad, wash with hot EtOAc",
+            "For residual Pd: stir with SiliaMetS Thiol (silica-bound thiol scavenger) or activated charcoal",
+            "For Ru (metathesis): DMSO treatment or PPh3 to decompose Ru, then filter through silica plug",
+            "For Cu (CuAAC, Chan-Lam): wash with sat. NH4Cl or EDTA solution",
+            "Column chromatography as final purification if metal contamination persists",
+        ],
+        "tips": "ICP-MS or ICP-OES for quantitative metal analysis in final product. Pd limit in pharmaceuticals: <10 ppm.",
+    },
+    "grignard_quench": {
+        "name": "Grignard/Organolithium Quench",
+        "when": "After Grignard or organolithium additions",
+        "steps": [
+            "Cool to 0°C",
+            "Quench SLOWLY with sat. NH4Cl(aq) (drop by drop initially)",
+            "Stir until clear bilayer forms (may need HCl if gel forms)",
+            "Separate, extract aqueous layer with organic solvent (2-3×)",
+            "Wash combined organics with brine, dry over Na2SO4, filter, concentrate",
+        ],
+        "tips": "For ketone products, sat. NH4Cl is mild enough to avoid epimerization. For acid-sensitive products, use sat. NaHCO3 instead. If thick emulsion: add more water, HCl until pH ~2, or filter through Celite.",
+    },
+    "swern_workup": {
+        "name": "Swern Oxidation Workup",
+        "when": "After Swern or related DMSO-based oxidations",
+        "steps": [
+            "Reaction mixture warms to RT after Et3N addition",
+            "Dilute with CH2Cl2, wash with water (2×)",
+            "Wash with 1M HCl (1×) to remove Et3N",
+            "Wash with sat. NaHCO3 (1×), brine (1×)",
+            "Dry over Na2SO4, filter, concentrate (fume hood — DMS smell!)",
+        ],
+        "tips": "Column chromatography usually needed. Me2S byproduct has strong odor — work in fume hood. Bleach trap for DMS waste.",
+    },
+}
+
+
+def lookup_workup(query: str) -> list[dict]:
+    """Search workup procedures by name or keyword."""
+    q = query.lower().strip()
+    results = []
+    for key, proc in WORKUP_PROCEDURES.items():
+        searchable = " ".join([proc["name"], proc["when"], key, " ".join(proc["steps"]), proc.get("tips", "")]).lower()
+        if q in searchable or q in key:
+            results.append(proc)
+    return results
+
+
+# =============================================================================
+# Solvent Guide
+# =============================================================================
+
+SOLVENTS: list[dict] = [
+    # Common organic solvents: name, bp, density, polarity_index, dielectric_constant, miscible_with_water, common_uses
+    {"name": "Pentane", "bp": 36, "density": 0.626, "polarity_index": 0.0, "dielectric": 1.84, "water_misc": False, "uses": "Column chromatography (non-polar), extractions", "safety": "Highly flammable, low flash point"},
+    {"name": "Hexane(s)", "bp": 69, "density": 0.659, "polarity_index": 0.1, "dielectric": 1.88, "water_misc": False, "uses": "Column chromatography, recrystallization solvent pair with EtOAc", "safety": "Flammable, neurotoxic (n-hexane)"},
+    {"name": "Heptane", "bp": 98, "density": 0.684, "polarity_index": 0.1, "dielectric": 1.92, "water_misc": False, "uses": "Column chromatography alternative to hexane, crystallization", "safety": "Flammable"},
+    {"name": "Cyclohexane", "bp": 81, "density": 0.779, "polarity_index": 0.2, "dielectric": 2.02, "water_misc": False, "uses": "Crystallization, NMR solvent (C6D12)", "safety": "Flammable"},
+    {"name": "Petroleum ether", "bp": "40-60", "density": 0.64, "polarity_index": 0.1, "dielectric": 1.9, "water_misc": False, "uses": "Column chromatography, extraction", "safety": "Highly flammable, mixture of hydrocarbons"},
+    {"name": "Diethyl ether", "bp": 35, "density": 0.713, "polarity_index": 2.8, "dielectric": 4.34, "water_misc": False, "uses": "Grignard reactions, extractions, crystallization. Forms peroxides!", "safety": "Extremely flammable, peroxide-forming, low bp"},
+    {"name": "MTBE (methyl tert-butyl ether)", "bp": 55, "density": 0.740, "polarity_index": 2.5, "dielectric": 2.6, "water_misc": False, "uses": "Extraction solvent (safer than Et2O), less prone to peroxides", "safety": "Flammable, but safer than Et2O"},
+    {"name": "THF", "bp": 66, "density": 0.889, "polarity_index": 4.0, "dielectric": 7.58, "water_misc": True, "uses": "Organometallic reactions, Grignard, LDA, universal solvent. Inhibited with BHT.", "safety": "Flammable, peroxide-forming. Distill from Na/benzophenone for dry THF."},
+    {"name": "2-MeTHF", "bp": 80, "density": 0.854, "polarity_index": 3.5, "dielectric": 6.97, "water_misc": False, "uses": "Green alternative to THF. Better phase separation. Organometallics.", "safety": "Flammable. Bio-derived."},
+    {"name": "1,4-Dioxane", "bp": 101, "density": 1.034, "polarity_index": 4.8, "dielectric": 2.25, "water_misc": True, "uses": "Pd cross-coupling, Buchwald-Hartwig. Good for high-temp reactions.", "safety": "Peroxide-forming, suspected carcinogen"},
+    {"name": "Dichloromethane (DCM)", "bp": 40, "density": 1.325, "polarity_index": 3.1, "dielectric": 8.93, "water_misc": False, "uses": "Extractions (heavier than water!), column chromatography, reactions at RT", "safety": "Not flammable but toxic (possible carcinogen). Denser than water."},
+    {"name": "Chloroform", "bp": 61, "density": 1.483, "polarity_index": 4.1, "dielectric": 4.81, "water_misc": False, "uses": "NMR solvent (CDCl3), extractions", "safety": "Toxic, possible carcinogen. Contains EtOH stabilizer. Denser than water."},
+    {"name": "1,2-Dichloroethane (DCE)", "bp": 83, "density": 1.253, "polarity_index": 3.5, "dielectric": 10.36, "water_misc": False, "uses": "Lewis acid reactions (higher bp alternative to DCM)", "safety": "Toxic, carcinogenic"},
+    {"name": "Ethyl acetate (EtOAc)", "bp": 77, "density": 0.902, "polarity_index": 4.4, "dielectric": 6.02, "water_misc": False, "uses": "Column chromatography, extraction, recrystallization", "safety": "Flammable, pleasant smell"},
+    {"name": "Acetone", "bp": 56, "density": 0.791, "polarity_index": 5.1, "dielectric": 20.7, "water_misc": True, "uses": "Cleaning glassware, Jones oxidation, dry ice baths, fast-evaporating", "safety": "Highly flammable"},
+    {"name": "Acetonitrile (MeCN)", "bp": 82, "density": 0.786, "polarity_index": 5.8, "dielectric": 37.5, "water_misc": True, "uses": "HPLC solvent, reactions with electrophilic reagents, Ritter reaction", "safety": "Flammable, toxic"},
+    {"name": "Methanol (MeOH)", "bp": 65, "density": 0.791, "polarity_index": 5.1, "dielectric": 32.7, "water_misc": True, "uses": "Recrystallization, hydrogenolysis, Zemplén deacetylation", "safety": "Flammable, toxic (blindness)"},
+    {"name": "Ethanol (EtOH)", "bp": 78, "density": 0.789, "polarity_index": 5.2, "dielectric": 24.5, "water_misc": True, "uses": "Recrystallization, green solvent, reactions", "safety": "Flammable"},
+    {"name": "Isopropanol (iPrOH)", "bp": 82, "density": 0.786, "polarity_index": 3.9, "dielectric": 17.9, "water_misc": True, "uses": "Cleaning, MPV reduction, crystallization", "safety": "Flammable"},
+    {"name": "DMF", "bp": 153, "density": 0.944, "polarity_index": 6.4, "dielectric": 36.7, "water_misc": True, "uses": "SN2 reactions, cross-coupling, peptide synthesis. Dissolves many salts.", "safety": "Reproductive toxin. Difficult to remove. Decomposes to Me2NH + CO at high temp with base."},
+    {"name": "DMA (N,N-dimethylacetamide)", "bp": 165, "density": 0.937, "polarity_index": 6.5, "dielectric": 37.8, "water_misc": True, "uses": "Alternative to DMF. Similar properties but slightly higher bp.", "safety": "Reproductive toxin"},
+    {"name": "NMP", "bp": 204, "density": 1.028, "polarity_index": 6.7, "dielectric": 32.2, "water_misc": True, "uses": "High-temp reactions, Stille coupling, polymer dissolution", "safety": "Reproductive toxin"},
+    {"name": "DMSO", "bp": 189, "density": 1.100, "polarity_index": 7.2, "dielectric": 46.7, "water_misc": True, "uses": "Swern oxidation, Kornblum oxidation, high-temp SNAr, DMSO-d6 NMR", "safety": "Penetrates skin rapidly (carries dissolved chemicals through skin!)"},
+    {"name": "Toluene", "bp": 111, "density": 0.867, "polarity_index": 2.4, "dielectric": 2.38, "water_misc": False, "uses": "Azeotropic drying (Dean-Stark), Grubbs metathesis, general non-polar solvent", "safety": "Flammable, toxic"},
+    {"name": "Benzene", "bp": 80, "density": 0.879, "polarity_index": 2.7, "dielectric": 2.28, "water_misc": False, "uses": "Legacy solvent (replaced by toluene). NMR (C6D6)", "safety": "Known carcinogen — avoid use!"},
+    {"name": "Xylene(s)", "bp": "138-144", "density": 0.860, "polarity_index": 2.5, "dielectric": 2.37, "water_misc": False, "uses": "High-temp reactions, histology", "safety": "Flammable, toxic"},
+    {"name": "Water", "bp": 100, "density": 1.000, "polarity_index": 10.2, "dielectric": 80.1, "water_misc": True, "uses": "Green solvent, aqueous reactions, on-water chemistry", "safety": "Non-toxic. Incompatible with many reagents."},
+    {"name": "Pyridine", "bp": 115, "density": 0.982, "polarity_index": 5.3, "dielectric": 12.4, "water_misc": True, "uses": "Base/solvent for acylations (Ac2O/py), nucleophilic catalysis, chromium oxidations", "safety": "Toxic, unpleasant smell, flammable"},
+    {"name": "Triethylamine (Et3N)", "bp": 89, "density": 0.726, "polarity_index": 1.8, "dielectric": 2.42, "water_misc": False, "uses": "Base (non-nucleophilic), Hünig's base alternative, scavenger for HX", "safety": "Flammable, corrosive, strong smell"},
+    {"name": "DIPEA (Hünig's base)", "bp": 127, "density": 0.742, "polarity_index": 2.0, "dielectric": 3.4, "water_misc": False, "uses": "Non-nucleophilic base, peptide coupling, cross-coupling", "safety": "Flammable"},
+    {"name": "HFIP (hexafluoroisopropanol)", "bp": 59, "density": 1.596, "polarity_index": 5.3, "dielectric": 16.7, "water_misc": True, "uses": "Strong H-bond donor, metal-free oxidations, hypervalent iodine chemistry", "safety": "Expensive, toxic"},
+    {"name": "TFE (trifluoroethanol)", "bp": 74, "density": 1.383, "polarity_index": 4.3, "dielectric": 26.7, "water_misc": True, "uses": "Acid-surrogate solvent, C-H activation, radical reactions", "safety": "Toxic"},
+]
+
+
+# Chromatography solvent systems
+CHROM_SOLVENT_SYSTEMS = [
+    {"system": "Hexanes / EtOAc", "range": "Non-polar to moderate", "notes": "Most common system. Start at 5% EtOAc, increase. Standard for general organic compounds."},
+    {"system": "Hexanes / Et2O", "range": "Non-polar to moderate", "notes": "Weaker eluent than EtOAc at same %. Good for separating hydrocarbons and halides."},
+    {"system": "Hexanes / Acetone", "range": "Non-polar to moderate", "notes": "Stronger eluent than EtOAc at same %. Good for polar compounds."},
+    {"system": "CH2Cl2 / MeOH", "range": "Moderate to very polar", "notes": "For polar compounds (amines, acids, amides). Start at 1-2% MeOH. Add 0.1% Et3N for basic compounds or 0.1% AcOH for acids."},
+    {"system": "CH2Cl2 / EtOAc", "range": "Moderate polarity", "notes": "Good intermediate polarity range. Useful when hex/EtOAc gradient is too shallow."},
+    {"system": "Toluene / EtOAc", "range": "Non-polar to moderate", "notes": "Alternative to hex/EtOAc. Better for UV-active compounds."},
+    {"system": "EtOAc / MeOH", "range": "Polar to very polar", "notes": "Very polar compounds. Use sparingly — can dissolve silica."},
+    {"system": "CHCl3 / MeOH / NH4OH", "range": "Very polar (amines)", "notes": "For very polar amines. Ratio: 90:9:1 to 80:18:2."},
+]
+
+
+def lookup_solvent(query: str) -> list[dict]:
+    """Search solvents by name, property, or use."""
+    q = query.lower().strip()
+    results = []
+    for s in SOLVENTS:
+        searchable = " ".join([s["name"], s["uses"], s.get("safety", "")]).lower()
+        if q in searchable:
+            results.append(s)
+    return results
+
+
+# =============================================================================
+# Cooling Baths
+# =============================================================================
+
+COOLING_BATHS: list[dict] = [
+    {"temp": 0, "recipe": "Ice / water", "notes": "Most common. Maintain ice:water ~2:1. Replace ice as needed."},
+    {"temp": -5, "recipe": "Ice / NaCl (rock salt)", "notes": "~1:3 salt:ice by mass."},
+    {"temp": -10, "recipe": "Ice / NaCl (rock salt)", "notes": "~1:3 salt:ice. Pack well."},
+    {"temp": -15, "recipe": "Ice / CaCl2 (anhydrous, 1:2.5 by mass)", "notes": "Calcium chloride/ice gives lower temp than NaCl/ice."},
+    {"temp": -20, "recipe": "Ice / NaCl (1:3 by mass)", "notes": "Or commercial -20°C freezer."},
+    {"temp": -40, "recipe": "Dry ice / acetonitrile", "notes": "Acetonitrile/dry ice slurry. bp(MeCN) = 82°C. Maintains -40°C."},
+    {"temp": -42, "recipe": "Dry ice / acetonitrile", "notes": "Acetonitrile/CO2 slurry."},
+    {"temp": -45, "recipe": "Dry ice / acetonitrile or dry ice / CH3CN", "notes": "Practical range -40 to -45°C."},
+    {"temp": -78, "recipe": "Dry ice / acetone", "notes": "THE standard low-temp bath. Sublimation temp of CO2. Add dry ice chunks to acetone. Replenish dry ice as needed."},
+    {"temp": -78, "recipe": "Dry ice / isopropanol", "notes": "Better thermal contact than dry ice/acetone. Same temp."},
+    {"temp": -84, "recipe": "Ethyl acetate / liquid N2", "notes": "EtOAc slush bath. Add LN2 slowly to EtOAc."},
+    {"temp": -94, "recipe": "Toluene / liquid N2", "notes": "Toluene slush. Add LN2 carefully to toluene."},
+    {"temp": -98, "recipe": "Methanol / liquid N2", "notes": "MeOH slush. Used for extremely low temp operations."},
+    {"temp": -116, "recipe": "Ethanol / liquid N2", "notes": "EtOH slush. Very low temperature."},
+    {"temp": -131, "recipe": "Pentane / liquid N2", "notes": "Pentane slush. Near LN2 temperatures."},
+    {"temp": -196, "recipe": "Liquid nitrogen", "notes": "Boiling point of N2. Use Dewar flask. Extremely cold — frostbite danger!"},
+    # Heat sources
+    {"temp": 40, "recipe": "Water bath", "notes": "Simple and precise. Use with rotovap."},
+    {"temp": 60, "recipe": "Water bath", "notes": "Good for gentle heating."},
+    {"temp": 80, "recipe": "Water bath or oil bath", "notes": "Near boiling water. Transition to oil bath."},
+    {"temp": 100, "recipe": "Boiling water bath or oil bath", "notes": "Steam bath for gentle reflux of many solvents."},
+    {"temp": 120, "recipe": "Oil bath (silicone or mineral oil)", "notes": "Standard oil bath range. Monitor with thermometer."},
+    {"temp": 150, "recipe": "Oil bath (silicone oil)", "notes": "Mid-range oil bath. Silicone oil to ~250°C."},
+    {"temp": 200, "recipe": "Oil bath or sand bath", "notes": "High-temp oil bath or sand bath. Mineral oil limit ~250°C."},
+    {"temp": 250, "recipe": "Sand bath or aluminum block", "notes": "Sand or metal heating block for high temp."},
+]
+
+
+def lookup_cooling_bath(target_temp: float | None = None) -> list[dict]:
+    """Find cooling/heating bath for target temperature. Returns closest options."""
+    if target_temp is None:
+        return COOLING_BATHS
+
+    # Sort by distance from target
+    sorted_baths = sorted(COOLING_BATHS, key=lambda b: abs(b["temp"] - target_temp))
+    return sorted_baths[:5]
+
+
+# =============================================================================
+# TLC Stains
+# =============================================================================
+
+TLC_STAINS: list[dict] = [
+    {
+        "name": "UV (254 nm)",
+        "detects": "Aromatic compounds, conjugated systems, any UV-active chromophore",
+        "recipe": "Use UV-active TLC plates (F254). Shine 254 nm UV lamp — spots appear dark on green background.",
+        "notes": "First method to try. Non-destructive. Does not detect saturated aliphatics. Short wavelength (254 nm) quenches plate fluorescence. Long wavelength (365 nm) for fluorescent compounds."
+    },
+    {
+        "name": "KMnO4 (Potassium permanganate)",
+        "detects": "Alkenes, alkynes, aldehydes, 1°/2° alcohols, most oxidizable compounds. UNIVERSAL stain.",
+        "recipe": "1.5 g KMnO4, 10 g K2CO3, 1.25 mL 10% NaOH, 200 mL water. Dip TLC plate, heat with heat gun.",
+        "notes": "Yellow spots on purple background. Most universal stain — use as default if unsure. Does NOT stain tertiary alcohols, alkyl halides, or non-oxidizable compounds."
+    },
+    {
+        "name": "p-Anisaldehyde",
+        "detects": "Almost everything: alcohols, terpenes, steroids, sugars, nucleosides. Multi-colored spots!",
+        "recipe": "135 mL EtOH + 5 mL conc. H2SO4 + 1.5 mL AcOH + 3.7 mL p-anisaldehyde. Dip, heat strongly.",
+        "notes": "Multi-colored stain (blue, purple, green, pink, orange) — very useful for distinguishing compounds. Keep refrigerated. Particularly good for terpenes, carbohydrates."
+    },
+    {
+        "name": "CAM (Ceric ammonium molybdate / Hanessian's stain)",
+        "detects": "Universal: alcohols, amines, ethers, most organics. Especially good for alcohol/amine mixtures.",
+        "recipe": "5 g ammonium molybdate + 2 g ceric sulfate in 200 mL 10% H2SO4. Dip, heat.",
+        "notes": "Dark blue/black spots on light blue background. Versatile and sensitive. Colors develop on heating."
+    },
+    {
+        "name": "PMA (Phosphomolybdic acid)",
+        "detects": "Universal: almost anything reducing. Especially lipids, steroids.",
+        "recipe": "10% phosphomolybdic acid in EtOH. Dip, heat.",
+        "notes": "Dark green/blue spots on yellow-green background. Very sensitive. Works for almost everything. Charring at high temp."
+    },
+    {
+        "name": "Vanillin",
+        "detects": "Alcohols, aldehydes, ketones, terpenes, terpenoids, higher MW compounds. Multi-colored.",
+        "recipe": "15 g vanillin + 250 mL EtOH + 2.5 mL conc. H2SO4. Dip, heat.",
+        "notes": "Multi-colored spots. Similar utility to anisaldehyde. Good for terpenes and steroids."
+    },
+    {
+        "name": "Ninhydrin",
+        "detects": "Primary amines, amino acids. Purple/pink spots ('Ruhemann's purple').",
+        "recipe": "0.3 g ninhydrin in 100 mL n-butanol + 3 mL AcOH. Dip, heat at 110°C.",
+        "notes": "Specific for amines. Proline/hydroxyproline give yellow. Secondary amines give brown/orange. Standard amino acid detection."
+    },
+    {
+        "name": "Dragendorff's reagent",
+        "detects": "Alkaloids, heterocyclic nitrogen compounds, quaternary ammonium compounds.",
+        "recipe": "Solution A: 0.85 g bismuth subnitrate in 10 mL AcOH + 40 mL H2O. Solution B: 8 g KI in 20 mL H2O. Mix A + B, add 20 mL AcOH + 100 mL H2O.",
+        "notes": "Orange/red spots on yellow background. Specific for nitrogen heterocycles."
+    },
+    {
+        "name": "DNP (2,4-Dinitrophenylhydrazine)",
+        "detects": "Aldehydes and ketones specifically.",
+        "recipe": "0.4 g 2,4-DNP in 2 mL H2SO4 + 30 mL EtOH + 10 mL H2O. Dip (no heating needed).",
+        "notes": "Orange/red spots. Highly specific for carbonyls. Classic qualitative test. Also used for derivatization for melting point ID."
+    },
+    {
+        "name": "Bromocresol green",
+        "detects": "Carboxylic acids and other acidic compounds.",
+        "recipe": "0.04 g bromocresol green in 100 mL EtOH + enough NaOH to make blue. Dip (no heating).",
+        "notes": "Yellow spots on blue background. Specific for acids. Non-destructive (at RT)."
+    },
+    {
+        "name": "Iodine chamber",
+        "detects": "Unsaturated compounds, aromatics, many organics. Reversible stain.",
+        "recipe": "Place a few crystals of I2 in a sealed chamber (jar with lid). Place TLC plate inside, wait.",
+        "notes": "Brown spots. Reversible — spots fade after removal from chamber. Non-destructive. Good for quick check."
+    },
+    {
+        "name": "Seebach's stain ('Magic stain')",
+        "detects": "Universal stain. Detects virtually all organic compounds.",
+        "recipe": "2.5 g phosphomolybdic acid + 1 g ceric sulfate + 6 mL conc. H2SO4 + 94 mL H2O. Dip, heat.",
+        "notes": "Multi-colored spots on green background. Combines PMA + CAN. Extremely versatile."
+    },
+    {
+        "name": "FeCl3 (Ferric chloride)",
+        "detects": "Phenols, enols, hydroxamic acids, sulfhydryl groups.",
+        "recipe": "1% FeCl3 in water or EtOH. Dip or spray.",
+        "notes": "Purple/blue/green/red spots depending on phenol structure. Classic phenol test."
+    },
+]
+
+
+def lookup_tlc_stain(query: str) -> list[dict]:
+    """Search TLC stains by name, functional group detected, or keyword."""
+    q = query.lower().strip()
+    results = []
+    for stain in TLC_STAINS:
+        searchable = " ".join([stain["name"], stain["detects"], stain.get("notes", "")]).lower()
+        if q in searchable:
+            results.append(stain)
+    # If no match, return all as reference
+    if not results and q in ("all", "list", "help", ""):
+        return TLC_STAINS
+    return results
+
+
+# =============================================================================
+# Column Chromatography Guide
+# =============================================================================
+
+COLUMN_GUIDE = {
+    "still_guidelines": {
+        "title": "Still's Flash Chromatography Guidelines (Still, Kahn, Mitra, JOC 1978)",
+        "rules": [
+            "Target Rf of 0.2-0.35 in your chosen solvent system (by TLC)",
+            "If Rf < 0.2: increase polarity; if Rf > 0.35: decrease polarity",
+            "Column diameter: use ~1 inch per 200 mg crude for easy separations",
+            "Silica height: 6 inches (15 cm) of silica for standard separation",
+            "Loading: ≤100:1 silica/crude (by mass) for difficult separations (ΔRf < 0.1)",
+            "Loading: ~30:1 silica/crude for easy separations (ΔRf > 0.2)",
+            "Apply sample as concentrated solution or dry-loaded on silica/Celite",
+            "Elute with ~10 column volumes of solvent",
+            "Collect fractions: ~5 mL per cm of column diameter",
+            "Use air pressure (flash) to maintain flow rate ~2 inches/min",
+        ],
+    },
+    "troubleshooting": [
+        {"problem": "Bands are streaking/tailing", "causes": "Overloaded column, compound too polar for system, acidic/basic compounds adsorbing to silica", "solutions": "Use less crude, increase polarity, add 0.1-1% Et3N (for amines) or 0.1-1% AcOH (for acids) to mobile phase. Try Florisil or alumina instead of silica."},
+        {"problem": "No separation (bands overlap)", "causes": "Rf values too similar, inadequate column length, wrong solvent system", "solutions": "Try different solvent systems (e.g., switch from hex/EtOAc to hex/acetone). Use longer column (more silica). Use smaller fractions."},
+        {"problem": "Product stuck on column", "causes": "Compound too polar, strong adsorption", "solutions": "Flush with high-polarity solvent (MeOH, then EtOAc+1%Et3N). Use reverse-phase or alumina."},
+        {"problem": "Fronting (leading edge)", "causes": "Sample overload, solvent mismatch", "solutions": "Load less material. Ensure loading solvent matches or is less polar than mobile phase."},
+        {"problem": "Poor recovery / decomposition on column", "causes": "Acid-sensitive compounds on silica (pH ~5-6), long contact time", "solutions": "Use deactivated silica (1-5% Et3N pretreated), basic alumina, or Florisil. Run column faster. Use MPLC."},
+        {"problem": "Baseline impurity co-eluting", "causes": "Silica dissolution, BHT from solvents, plasticizer from tubing", "solutions": "Use distilled solvents. Avoid PVC tubing. Pre-rinse column with mobile phase."},
+    ],
+    "column_sizes": [
+        {"diameter_cm": 1.0, "crude_mg": "40-100", "silica_g": "4-10", "fraction_ml": "3-5"},
+        {"diameter_cm": 1.5, "crude_mg": "100-200", "silica_g": "10-20", "fraction_ml": "5-8"},
+        {"diameter_cm": 2.0, "crude_mg": "200-400", "silica_g": "20-40", "fraction_ml": "8-12"},
+        {"diameter_cm": 2.5, "crude_mg": "400-800", "silica_g": "40-80", "fraction_ml": "12-15"},
+        {"diameter_cm": 3.0, "crude_mg": "800-1200", "silica_g": "60-120", "fraction_ml": "15-20"},
+        {"diameter_cm": 4.0, "crude_mg": "1200-2000", "silica_g": "100-200", "fraction_ml": "20-30"},
+        {"diameter_cm": 5.0, "crude_mg": "2000-5000", "silica_g": "200-500", "fraction_ml": "30-50"},
+    ],
+    "rf_rules": [
+        "Rf = distance traveled by compound / distance traveled by solvent front",
+        "Rf is reproducible only if: same silica, same chamber saturation, same temperature",
+        "Rf 0.0-0.1: too polar for this system — increase mobile phase polarity",
+        "Rf 0.1-0.2: acceptable but slow elution — consider more polar system",
+        "Rf 0.2-0.35: IDEAL range for column chromatography",
+        "Rf 0.35-0.5: OK for easy separations or gradient",
+        "Rf 0.5-1.0: compound too non-polar for this system — decrease polarity",
+        "If two spots have ΔRf ≥ 0.15: easy separation (~20:1 silica:crude)",
+        "If ΔRf ≈ 0.1: moderate separation (~50:1 silica:crude)",
+        "If ΔRf < 0.05: difficult separation (consider different system, gradient, or prep HPLC)",
+    ],
+    "dry_loading": {
+        "description": "Dry loading (preferred for best resolution)",
+        "steps": [
+            "Dissolve crude in minimum volume of CH2Cl2 or EtOAc",
+            "Add ~2× mass Celite or silica gel (relative to crude)",
+            "Evaporate solvent on rotovap → free-flowing powder",
+            "Add powder on top of packed column (below sand layer)",
+            "This gives a narrow initial band → better resolution",
+        ],
+    },
+}
+
+
+def lookup_column_guide(query: str) -> dict | list:
+    """Search column chromatography guide by topic."""
+    q = query.lower().strip()
+    if "still" in q or "guideline" in q or "rule" in q or "general" in q:
+        return COLUMN_GUIDE["still_guidelines"]
+    if "troubleshoot" in q or "problem" in q or "streak" in q or "tail" in q:
+        return COLUMN_GUIDE["troubleshooting"]
+    if "size" in q or "diameter" in q or "how much silica" in q:
+        return COLUMN_GUIDE["column_sizes"]
+    if "rf" in q or "retention" in q:
+        return COLUMN_GUIDE["rf_rules"]
+    if "dry load" in q or "loading" in q:
+        return COLUMN_GUIDE["dry_loading"]
+    if "solvent" in q or "system" in q or "eluent" in q:
+        return CHROM_SOLVENT_SYSTEMS
+    # Return everything
+    return COLUMN_GUIDE
+
+
+# =============================================================================
+# Buffer Recipes — 25 common laboratory buffers
+# =============================================================================
+
+BUFFER_RECIPES: list[dict] = [
+    {
+        "name": "PBS (Phosphate-Buffered Saline)",
+        "pH": "7.4",
+        "recipe": "137 mM NaCl, 2.7 mM KCl, 10 mM Na₂HPO₄, 1.8 mM KH₂PO₄",
+        "preparation": "Dissolve 8.0 g NaCl, 0.2 g KCl, 1.44 g Na₂HPO₄, 0.24 g KH₂PO₄ in 800 mL dH₂O. Adjust pH to 7.4 with HCl. Add water to 1 L. Autoclave.",
+        "category": "physiological",
+        "pKa": 7.20,
+        "range": "6.2–8.2",
+        "notes": "Most common biological buffer. Do NOT use with Ca²⁺/Mg²⁺-sensitive assays (phosphate chelates divalent cations).",
+    },
+    {
+        "name": "10× PBS",
+        "pH": "7.4",
+        "recipe": "1.37 M NaCl, 27 mM KCl, 100 mM Na₂HPO₄, 18 mM KH₂PO₄",
+        "preparation": "Dissolve 80 g NaCl, 2 g KCl, 14.4 g Na₂HPO₄, 2.4 g KH₂PO₄ in 800 mL dH₂O. Adjust pH. Add water to 1 L.",
+        "category": "physiological",
+        "pKa": 7.20,
+        "range": "6.2–8.2",
+        "notes": "Dilute 1:10 before use. Check pH after dilution.",
+    },
+    {
+        "name": "TBS (Tris-Buffered Saline)",
+        "pH": "7.6",
+        "recipe": "20 mM Tris-HCl, 150 mM NaCl",
+        "preparation": "Dissolve 2.42 g Tris base + 8.77 g NaCl in 900 mL dH₂O. Adjust pH to 7.6 with conc. HCl (~3.2 mL). Add water to 1 L.",
+        "category": "physiological",
+        "pKa": 8.07,
+        "range": "7.0–9.0",
+        "notes": "Alternative to PBS when phosphate interferes. Tris pKa is temperature-sensitive: ΔpKa/°C = −0.031.",
+    },
+    {
+        "name": "Tris-HCl",
+        "pH": "7.4–8.8",
+        "recipe": "50 mM Tris-HCl",
+        "preparation": "Dissolve 6.06 g Tris base in 800 mL dH₂O. Adjust pH with conc. HCl at the working temperature. Add water to 1 L.",
+        "category": "general",
+        "pKa": 8.07,
+        "range": "7.0–9.0",
+        "notes": "Adjust pH at working temperature (pKa drops ~0.03/°C). Common for protein purification, electrophoresis.",
+    },
+    {
+        "name": "HEPES",
+        "pH": "7.2–7.6",
+        "recipe": "25 mM HEPES",
+        "preparation": "Dissolve 5.96 g HEPES in 900 mL dH₂O. Adjust pH with NaOH. Add water to 1 L.",
+        "category": "biological",
+        "pKa": 7.55,
+        "range": "6.8–8.2",
+        "notes": "Good's buffer. Minimal metal binding. Preferred for cell culture. Does not interfere with BCA assay.",
+    },
+    {
+        "name": "MES",
+        "pH": "5.5–6.7",
+        "recipe": "50 mM MES",
+        "preparation": "Dissolve 9.76 g MES in 900 mL dH₂O. Adjust pH with NaOH. Add water to 1 L.",
+        "category": "biological",
+        "pKa": 6.15,
+        "range": "5.5–6.7",
+        "notes": "Good's buffer for slightly acidic conditions. Useful for ion-exchange chromatography.",
+    },
+    {
+        "name": "MOPS",
+        "pH": "6.5–7.9",
+        "recipe": "20 mM MOPS",
+        "preparation": "Dissolve 4.19 g MOPS in 900 mL dH₂O. Adjust pH with NaOH. Add water to 1 L.",
+        "category": "biological",
+        "pKa": 7.20,
+        "range": "6.5–7.9",
+        "notes": "Good's buffer. Common for RNA gel electrophoresis (MOPS buffer = 20 mM MOPS, 5 mM NaOAc, 1 mM EDTA, pH 7.0).",
+    },
+    {
+        "name": "PIPES",
+        "pH": "6.1–7.5",
+        "recipe": "25 mM PIPES",
+        "preparation": "Dissolve 7.56 g PIPES in 900 mL dH₂O. May need slight warming to dissolve. Adjust pH with NaOH. Add water to 1 L.",
+        "category": "biological",
+        "pKa": 6.76,
+        "range": "6.1–7.5",
+        "notes": "Good's buffer. Low metal binding. Relatively insoluble in water — dissolve with NaOH.",
+    },
+    {
+        "name": "Citrate buffer",
+        "pH": "3.0–6.2",
+        "recipe": "0.1 M citric acid / 0.1 M sodium citrate",
+        "preparation": "Mix 0.1 M citric acid (21.01 g/L) with 0.1 M trisodium citrate dihydrate (29.41 g/L) to desired pH.",
+        "category": "general",
+        "pKa": 3.13,
+        "range": "3.0–6.2",
+        "notes": "Triprotic: pKa₁=3.13, pKa₂=4.76, pKa₃=6.40. Chelates metals. Common for protein crystallization.",
+    },
+    {
+        "name": "Acetate buffer",
+        "pH": "3.6–5.6",
+        "recipe": "0.1 M acetic acid / 0.1 M sodium acetate",
+        "preparation": "Mix 0.1 M acetic acid (5.72 mL glacial AcOH/L) with 0.1 M NaOAc (8.20 g/L) to desired pH.",
+        "category": "general",
+        "pKa": 4.76,
+        "range": "3.6–5.6",
+        "notes": "Volatile — good for mass spectrometry. Common for protein purification at acidic pH.",
+    },
+    {
+        "name": "Phosphate buffer (Sørensen)",
+        "pH": "5.8–8.0",
+        "recipe": "Varies — mix monobasic + dibasic sodium phosphate",
+        "preparation": "Mix 0.2 M NaH₂PO₄ (27.60 g/L) with 0.2 M Na₂HPO₄ (28.39 g/L) in ratios from tables to desired pH.",
+        "category": "general",
+        "pKa": 7.20,
+        "range": "5.8–8.0",
+        "notes": "Autoclavable. Avoid with proteins sensitive to phosphate. Precipitates with Ca²⁺, Mg²⁺, Mn²⁺, Fe³⁺.",
+    },
+    {
+        "name": "Carbonate-bicarbonate buffer",
+        "pH": "9.2–10.8",
+        "recipe": "0.1 M Na₂CO₃ / 0.1 M NaHCO₃",
+        "preparation": "Mix 0.1 M Na₂CO₃ (10.60 g/L) with 0.1 M NaHCO₃ (8.40 g/L) to desired pH.",
+        "category": "general",
+        "pKa": 10.33,
+        "range": "9.2–10.8",
+        "notes": "High pH buffer. Common for ELISA coating. CO₂ loss shifts pH — keep sealed.",
+    },
+    {
+        "name": "Glycine-HCl",
+        "pH": "2.2–3.6",
+        "recipe": "0.1 M glycine adjusted with HCl",
+        "preparation": "Dissolve 7.51 g glycine in 900 mL dH₂O. Adjust pH with conc. HCl. Add water to 1 L.",
+        "category": "general",
+        "pKa": 2.35,
+        "range": "2.2–3.6",
+        "notes": "Common for protein elution from affinity columns (low pH elution).",
+    },
+    {
+        "name": "TAE (Tris-Acetate-EDTA)",
+        "pH": "8.0",
+        "recipe": "40 mM Tris, 20 mM acetic acid, 1 mM EDTA",
+        "preparation": "50×: 242 g Tris base + 57.1 mL glacial acetic acid + 100 mL 0.5 M EDTA pH 8.0 → 1 L. Dilute 1:50.",
+        "category": "electrophoresis",
+        "pKa": 8.07,
+        "range": "7.5–8.5",
+        "notes": "DNA gel electrophoresis. Better resolution than TBE but lower buffering capacity.",
+    },
+    {
+        "name": "TBE (Tris-Borate-EDTA)",
+        "pH": "8.3",
+        "recipe": "89 mM Tris, 89 mM boric acid, 2 mM EDTA",
+        "preparation": "10×: 108 g Tris base + 55 g boric acid + 40 mL 0.5 M EDTA pH 8.0 → 1 L. Dilute 1:10.",
+        "category": "electrophoresis",
+        "pKa": 8.07,
+        "range": "8.0–8.5",
+        "notes": "DNA/RNA gel electrophoresis. Higher buffering capacity than TAE. Better for small fragments (<1 kb).",
+    },
+    {
+        "name": "SDS-PAGE running buffer (Laemmli)",
+        "pH": "8.3",
+        "recipe": "25 mM Tris, 192 mM glycine, 0.1% SDS",
+        "preparation": "10×: 30.3 g Tris base + 144 g glycine + 10 g SDS → 1 L dH₂O. Dilute 1:10. Do NOT adjust pH.",
+        "category": "electrophoresis",
+        "pKa": 8.07,
+        "range": "8.3",
+        "notes": "Tris-glycine system for SDS-PAGE. pH is set by the buffer combination — do NOT add acid/base.",
+    },
+    {
+        "name": "Western transfer buffer (Towbin)",
+        "pH": "8.3",
+        "recipe": "25 mM Tris, 192 mM glycine, 20% methanol",
+        "preparation": "3.03 g Tris base + 14.4 g glycine + 200 mL methanol → 1 L dH₂O. Do NOT adjust pH.",
+        "category": "electrophoresis",
+        "pKa": 8.07,
+        "range": "8.3",
+        "notes": "For Western blot transfer. Methanol helps protein binding to membrane. Reduce to 10% for large proteins (>100 kDa).",
+    },
+    {
+        "name": "TE buffer",
+        "pH": "8.0",
+        "recipe": "10 mM Tris-HCl pH 8.0, 1 mM EDTA",
+        "preparation": "Mix 1 mL 1 M Tris-HCl pH 8.0 + 0.2 mL 0.5 M EDTA pH 8.0 → 100 mL dH₂O. Autoclave.",
+        "category": "nucleic acid",
+        "pKa": 8.07,
+        "range": "7.5–8.5",
+        "notes": "Standard DNA/RNA storage buffer. EDTA chelates nucleases. Use TE-low (0.1 mM EDTA) for PCR templates.",
+    },
+    {
+        "name": "RIPA lysis buffer",
+        "pH": "7.4",
+        "recipe": "50 mM Tris-HCl pH 7.4, 150 mM NaCl, 1% NP-40, 0.5% sodium deoxycholate, 0.1% SDS",
+        "preparation": "Mix components in dH₂O. Add protease inhibitors fresh before use.",
+        "category": "lysis",
+        "pKa": 8.07,
+        "range": "7.0–8.0",
+        "notes": "Strong lysis for total protein extraction. Add protease + phosphatase inhibitors fresh. Keep on ice.",
+    },
+    {
+        "name": "Lysis buffer (mild, NP-40)",
+        "pH": "7.4",
+        "recipe": "50 mM Tris-HCl pH 7.4, 150 mM NaCl, 1% NP-40",
+        "preparation": "Mix components in dH₂O. Add protease inhibitors fresh before use.",
+        "category": "lysis",
+        "pKa": 8.07,
+        "range": "7.0–8.0",
+        "notes": "Mild lysis preserving protein-protein interactions. Good for co-IP.",
+    },
+]
+
+
+def lookup_buffer(query: str) -> list[dict]:
+    """Search buffer recipes by name, pH range, category, or keyword."""
+    q = query.lower().strip()
+    results = []
+    for buf in BUFFER_RECIPES:
+        searchable = f"{buf['name']} {buf.get('category', '')} {buf.get('notes', '')} {buf.get('recipe', '')}".lower()
+        if q in searchable:
+            results.append(buf)
+    # If no exact match, try individual words
+    if not results:
+        words = q.split()
+        for buf in BUFFER_RECIPES:
+            searchable = f"{buf['name']} {buf.get('category', '')} {buf.get('notes', '')}".lower()
+            if all(w in searchable for w in words):
+                results.append(buf)
+    # Try pH range
+    if not results:
+        try:
+            target_ph = float(q)
+            for buf in BUFFER_RECIPES:
+                try:
+                    low, high = buf["range"].split("–")
+                    if float(low) <= target_ph <= float(high):
+                        results.append(buf)
+                except (ValueError, KeyError):
+                    pass
+        except ValueError:
+            pass
+    return results
+
+
+# =============================================================================
+# Amino Acid Properties — 20 canonical + common modifications
+# =============================================================================
+
+AMINO_ACIDS: list[dict] = [
+    {"code1": "G", "code3": "Gly", "name": "Glycine",       "mw": 57.02,  "pKa_carboxyl": 2.35, "pKa_amino": 9.78, "pKa_side": None,  "pI": 5.97, "hydropathy": -0.4,  "class": "nonpolar",   "notes": "Smallest AA. Achiral. Flexible — disrupts helices."},
+    {"code1": "A", "code3": "Ala", "name": "Alanine",       "mw": 71.04,  "pKa_carboxyl": 2.34, "pKa_amino": 9.87, "pKa_side": None,  "pI": 6.01, "hydropathy": 1.8,   "class": "nonpolar",   "notes": "Strong helix former. Reference for hydrophobicity scales."},
+    {"code1": "V", "code3": "Val", "name": "Valine",        "mw": 99.07,  "pKa_carboxyl": 2.29, "pKa_amino": 9.74, "pKa_side": None,  "pI": 5.97, "hydropathy": 4.2,   "class": "nonpolar",   "notes": "Branched-chain AA. Beta-branched — disfavors helix."},
+    {"code1": "L", "code3": "Leu", "name": "Leucine",       "mw": 113.08, "pKa_carboxyl": 2.33, "pKa_amino": 9.74, "pKa_side": None,  "pI": 5.98, "hydropathy": 3.8,   "class": "nonpolar",   "notes": "Most abundant AA in proteins. Strong helix former."},
+    {"code1": "I", "code3": "Ile", "name": "Isoleucine",    "mw": 113.08, "pKa_carboxyl": 2.32, "pKa_amino": 9.76, "pKa_side": None,  "pI": 6.02, "hydropathy": 4.5,   "class": "nonpolar",   "notes": "Beta-branched. Two chiral centers. Most hydrophobic canonical AA."},
+    {"code1": "P", "code3": "Pro", "name": "Proline",       "mw": 97.05,  "pKa_carboxyl": 1.95, "pKa_amino": 10.64, "pKa_side": None, "pI": 6.48, "hydropathy": -1.6,  "class": "nonpolar",   "notes": "Cyclic (imino acid). Helix breaker. cis-trans isomerism. Rigid."},
+    {"code1": "F", "code3": "Phe", "name": "Phenylalanine", "mw": 147.07, "pKa_carboxyl": 2.20, "pKa_amino": 9.31, "pKa_side": None,  "pI": 5.49, "hydropathy": 2.8,   "class": "aromatic",   "notes": "UV absorbs weakly at 257 nm. Aromatic π-stacking."},
+    {"code1": "W", "code3": "Trp", "name": "Tryptophan",    "mw": 186.08, "pKa_carboxyl": 2.46, "pKa_amino": 9.41, "pKa_side": None,  "pI": 5.89, "hydropathy": -0.9,  "class": "aromatic",   "notes": "Largest AA. UV absorbs at 280 nm (ε=5500). Rare in proteins. Fluorescent (λex=295, λem=348 nm)."},
+    {"code1": "M", "code3": "Met", "name": "Methionine",    "mw": 131.04, "pKa_carboxyl": 2.13, "pKa_amino": 9.28, "pKa_side": None,  "pI": 5.74, "hydropathy": 1.9,   "class": "nonpolar",   "notes": "Start codon (AUG). Thioether side chain. Easily oxidized to sulfoxide."},
+    {"code1": "S", "code3": "Ser", "name": "Serine",        "mw": 87.03,  "pKa_carboxyl": 2.19, "pKa_amino": 9.21, "pKa_side": None,  "pI": 5.68, "hydropathy": -0.8,  "class": "polar uncharged", "notes": "Phosphorylation site. Active site nucleophile (serine proteases)."},
+    {"code1": "T", "code3": "Thr", "name": "Threonine",     "mw": 101.05, "pKa_carboxyl": 2.09, "pKa_amino": 9.10, "pKa_side": None,  "pI": 5.60, "hydropathy": -0.7,  "class": "polar uncharged", "notes": "Phosphorylation site. Beta-branched. Two chiral centers."},
+    {"code1": "C", "code3": "Cys", "name": "Cysteine",      "mw": 103.01, "pKa_carboxyl": 1.92, "pKa_amino": 10.70, "pKa_side": 8.37, "pI": 5.07, "hydropathy": 2.5,   "class": "polar uncharged", "notes": "Disulfide bonds (S-S). Strong nucleophile (thiol). UV: ε_280=125 (disulfide). Sensitive to oxidation."},
+    {"code1": "Y", "code3": "Tyr", "name": "Tyrosine",      "mw": 163.06, "pKa_carboxyl": 2.20, "pKa_amino": 9.21, "pKa_side": 10.46, "pI": 5.66, "hydropathy": -1.3, "class": "aromatic",   "notes": "Phosphorylation site. UV absorbs at 280 nm (ε=1490). Phenol OH."},
+    {"code1": "H", "code3": "His", "name": "Histidine",     "mw": 137.06, "pKa_carboxyl": 1.78, "pKa_amino": 9.18, "pKa_side": 6.04,  "pI": 7.59, "hydropathy": -3.2,  "class": "positively charged", "notes": "Imidazole (pKa ≈ 6). Protonated at physiological pH ~10%. Acid-base catalysis. Metal coordination (Zn, Cu, Fe)."},
+    {"code1": "K", "code3": "Lys", "name": "Lysine",        "mw": 128.09, "pKa_carboxyl": 2.16, "pKa_amino": 9.06, "pKa_side": 10.54, "pI": 9.74, "hydropathy": -3.9,  "class": "positively charged", "notes": "Charged at physiological pH. Ubiquitination, acetylation, methylation target."},
+    {"code1": "R", "code3": "Arg", "name": "Arginine",      "mw": 156.10, "pKa_carboxyl": 1.82, "pKa_amino": 8.99, "pKa_side": 12.48, "pI": 10.76, "hydropathy": -4.5, "class": "positively charged", "notes": "Guanidinium — always charged at physiological pH. Strongest base among AAs. Salt bridges."},
+    {"code1": "D", "code3": "Asp", "name": "Aspartate",     "mw": 115.03, "pKa_carboxyl": 1.99, "pKa_amino": 9.90, "pKa_side": 3.90,  "pI": 2.77, "hydropathy": -3.5,  "class": "negatively charged", "notes": "Carboxylate side chain. Metal coordination. Succinimide formation with adjacent Asn/Ser."},
+    {"code1": "E", "code3": "Glu", "name": "Glutamate",     "mw": 129.04, "pKa_carboxyl": 2.10, "pKa_amino": 9.47, "pKa_side": 4.07,  "pI": 3.22, "hydropathy": -3.5,  "class": "negatively charged", "notes": "Carboxylate. Neurotransmitter. Strong helix former. Longer side chain than Asp."},
+    {"code1": "N", "code3": "Asn", "name": "Asparagine",    "mw": 114.04, "pKa_carboxyl": 2.14, "pKa_amino": 8.72, "pKa_side": None,  "pI": 5.41, "hydropathy": -3.5,  "class": "polar uncharged", "notes": "Amide side chain. N-glycosylation site (Asn-X-Ser/Thr). Deamidation-prone."},
+    {"code1": "Q", "code3": "Gln", "name": "Glutamine",     "mw": 128.06, "pKa_carboxyl": 2.17, "pKa_amino": 9.13, "pKa_side": None,  "pI": 5.65, "hydropathy": -3.5,  "class": "polar uncharged", "notes": "Amide side chain. Deamidation-prone (→ Glu). Polyglutamine expansions in disease."},
+]
+
+# Build lookup dicts
+_AA_BY_CODE1 = {aa["code1"]: aa for aa in AMINO_ACIDS}
+_AA_BY_CODE3 = {aa["code3"].lower(): aa for aa in AMINO_ACIDS}
+_AA_BY_NAME = {aa["name"].lower(): aa for aa in AMINO_ACIDS}
+
+
+def lookup_amino_acid(query: str) -> list[dict]:
+    """Look up amino acid by 1-letter code, 3-letter code, name, or property class."""
+    q = query.strip()
+
+    # Single character → 1-letter code
+    if len(q) == 1:
+        aa = _AA_BY_CODE1.get(q.upper())
+        return [aa] if aa else []
+
+    # 3-letter code
+    aa = _AA_BY_CODE3.get(q.lower())
+    if aa:
+        return [aa]
+
+    # Full name
+    aa = _AA_BY_NAME.get(q.lower())
+    if aa:
+        return [aa]
+
+    # Class or property search
+    q_lower = q.lower()
+    results = []
+    for aa in AMINO_ACIDS:
+        searchable = f"{aa['name']} {aa['class']} {aa.get('notes', '')}".lower()
+        if q_lower in searchable:
+            results.append(aa)
+
+    # If "all" or empty — return everything
+    if not results and q_lower in ("all", "table", "list", ""):
+        return AMINO_ACIDS
+
+    return results
+
+
+# =============================================================================
+# NMR Solvent Reference — residual solvent peaks for common NMR solvents
+# =============================================================================
+
+NMR_SOLVENTS: list[dict] = [
+    {"name": "Chloroform-d", "formula": "CDCl₃", "abbrev": "CDCl3",
+     "h_residual": 7.26, "c_residual": 77.16, "c_multiplicity": "triplet",
+     "bp": 61, "density": 1.492, "water_peak": 1.56,
+     "notes": "Most common NMR solvent. Dissolves most organic compounds. Slightly acidic — avoid with base-sensitive compounds."},
+    {"name": "DMSO-d₆", "formula": "(CD₃)₂SO", "abbrev": "DMSO-d6",
+     "h_residual": 2.50, "c_residual": 39.52, "c_multiplicity": "septet",
+     "bp": 189, "density": 1.190, "water_peak": 3.33,
+     "notes": "Universal solvent. Hygroscopic. High bp — hard to remove. Dissolves salts, peptides, polymers."},
+    {"name": "Methanol-d₄", "formula": "CD₃OD", "abbrev": "MeOD",
+     "h_residual": 3.31, "c_residual": 49.00, "c_multiplicity": "septet",
+     "bp": 65, "density": 0.888, "water_peak": 4.87,
+     "notes": "Good for polar compounds. Exchangeable protons (OH, NH) disappear. Two residual peaks: 3.31 (CHD₂) and 4.87 (OH)."},
+    {"name": "D₂O", "formula": "D₂O", "abbrev": "D2O",
+     "h_residual": 4.79, "c_residual": None, "c_multiplicity": None,
+     "bp": 101, "density": 1.107, "water_peak": 4.79,
+     "notes": "For water-soluble compounds. No ¹³C reference — use external standard (DSS, TSP). Exchangeable protons disappear. pH-dependent HDO peak."},
+    {"name": "Acetone-d₆", "formula": "(CD₃)₂CO", "abbrev": "acetone-d6",
+     "h_residual": 2.05, "c_residual": 29.84, "c_multiplicity": "septet",
+     "bp": 56, "density": 0.872, "water_peak": 2.84,
+     "notes": "Good for moderately polar compounds. Carbonyl ¹³C at 206.26 ppm. Low viscosity → sharp peaks."},
+    {"name": "Acetonitrile-d₃", "formula": "CD₃CN", "abbrev": "MeCN-d3",
+     "h_residual": 1.94, "c_residual": 1.32, "c_multiplicity": "septet",
+     "bp": 82, "density": 0.844, "water_peak": 2.13,
+     "notes": "Good for small molecules. CN carbon at 118.26 ppm. Low viscosity."},
+    {"name": "Benzene-d₆", "formula": "C₆D₆", "abbrev": "C6D6",
+     "h_residual": 7.16, "c_residual": 128.06, "c_multiplicity": "triplet",
+     "bp": 80, "density": 0.950, "water_peak": 0.40,
+     "notes": "Aromatic solvent. Shifts aromatic peaks upfield (ASIS effect). Carcinogen — handle with care."},
+    {"name": "THF-d₈", "formula": "C₄D₈O", "abbrev": "THF-d8",
+     "h_residual": "1.72, 3.58", "c_residual": "25.31, 67.21", "c_multiplicity": "quintets",
+     "bp": 66, "density": 0.985, "water_peak": 2.46,
+     "notes": "Good for organometallics, air-sensitive chemistry. Two sets of peaks (α and β CH₂)."},
+    {"name": "DCM-d₂", "formula": "CD₂Cl₂", "abbrev": "CD2Cl2",
+     "h_residual": 5.32, "c_residual": 53.84, "c_multiplicity": "quintet",
+     "bp": 40, "density": 1.350, "water_peak": 1.52,
+     "notes": "Similar to CDCl₃ but lower bp. Good for low-temperature NMR. Less acidic than CDCl₃."},
+    {"name": "DMF-d₇", "formula": "(CD₃)₂NCDO", "abbrev": "DMF-d7",
+     "h_residual": "2.75, 2.92, 8.03", "c_residual": "29.76, 34.89, 162.62", "c_multiplicity": "various",
+     "bp": 153, "density": 1.044, "water_peak": 3.49,
+     "notes": "Polar aprotic. Three residual ¹H peaks. Good for peptides, salts, organometallics."},
+    {"name": "Pyridine-d₅", "formula": "C₅D₅N", "abbrev": "py-d5",
+     "h_residual": "7.22, 7.58, 8.74", "c_residual": "123.87, 135.91, 149.90", "c_multiplicity": "triplets",
+     "bp": 115, "density": 1.046, "water_peak": 4.95,
+     "notes": "Basic solvent. Dissolves carbohydrates, nucleosides. Three ¹H residual peaks."},
+    {"name": "TFA-d", "formula": "CF₃COOD", "abbrev": "TFA-d",
+     "h_residual": 11.50, "c_residual": "116.6, 164.2", "c_multiplicity": "quartets (¹⁹F coupling)",
+     "bp": 72, "density": 1.485, "water_peak": None,
+     "notes": "Strong acid solvent. ¹³C shows quartets from ¹⁹F coupling. Dissolves peptides, proteins."},
+]
+
+
+def lookup_nmr_solvent(query: str) -> list[dict]:
+    """Search NMR solvent reference by name or abbreviation."""
+    q = query.lower().strip()
+    results = []
+    for sol in NMR_SOLVENTS:
+        searchable = f"{sol['name']} {sol['abbrev']} {sol['formula']} {sol.get('notes', '')}".lower()
+        if q in searchable:
+            results.append(sol)
+    if not results and q in ("all", "table", "list", ""):
+        return NMR_SOLVENTS
+    return results