Glossary

Definitions of the key technical terms used throughout the book. Alphabetical order. Each entry cross-references the chapter where the term receives its primary treatment.

Acetal — Geminal diether: R-CH(OR')₂. Formed from aldehyde + 2 alcohols (acid-catalyzed). Used as protecting group for aldehydes (Ch 25).

Activating group — Substituent on an aromatic ring that increases its reactivity toward electrophiles (e.g., -OH, -NH₂, -OR, alkyl). Generally electron-donating; o/p-directing (Ch 22). Compare deactivating group.

Activation energy (E_a) — Energy barrier between reactants and TS (Ch 5). Determines reaction rate via Arrhenius.

Addition (1,2 vs 1,4) — Two modes of attack on an α,β-unsaturated carbonyl or a conjugated diene. 1,2 = direct (kinetic, hard Nu); 1,4 = conjugate (thermodynamic, soft Nu) (Chs 19, 29).

Alcohol — R-OH. Classified primary, secondary, tertiary by attached carbons (Ch 4).

Aldol reaction — Enolate + carbonyl → β-hydroxy carbonyl (Ch 28).

Alder endo rule — In Diels-Alder reactions, the endo transition state (substituents tucked under the diene) is kinetically preferred over exo because of secondary orbital interactions (Ch 19).

Alkene — Hydrocarbon containing a C=C double bond. Sp² carbons (Ch 15).

Alkoxide — Conjugate base of an alcohol: R-O⁻. Strong base, good nucleophile (Chs 3, 10).

Alkyl halide — R-X where X = F, Cl, Br, I. Substrates for SN and E reactions (Chs 10-14).

Alkyne — Hydrocarbon containing a C≡C triple bond. Sp carbons (Ch 17).

Alkynide — Conjugate base of a terminal alkyne: R-C≡C⁻. Strong base, excellent C-nucleophile (Ch 17).

Allyl — The -CH₂-CH=CH₂ group, or anything adjacent to C=C (Ch 18).

Allylic — Adjacent to a C=C bond. Allylic cations and radicals are resonance-stabilized (Ch 18).

Ambident nucleophile — A nucleophile with two reactive sites of different character (e.g., enolate C vs O; CN⁻ C vs N) (Ch 27).

Amide — R-C(=O)-NR'R''. Least reactive carbonyl (Chs 24, 26).

Amine — R-NH₂ (primary), R₂NH (secondary), R₃N (tertiary). Base, nucleophile (Ch 30).

Anchimeric assistance — Neighboring group participation; an internal Nu briefly bonds to the reaction center, accelerating substitution and influencing stereochemistry (Ch 11).

Anion — Negatively charged species.

Anomer — α/β forms of cyclic sugar differing at anomeric (C1) carbon (Ch 32).

Anti — Functional groups on opposite faces or 180° apart in a Newman projection. Anti addition places two new bonds on opposite faces (Chs 5, 8, 16).

Antiaromatic — Cyclic, planar, fully conjugated, 4n π electrons. Destabilized relative to the open analog (Ch 20).

Anti-periplanar — Dihedral angle 180°, on opposite faces of C-C bond. Required for E2 (Ch 12).

Aprotic solvent — Solvent without -OH or -NH (no exchangeable H to H-bond donate). Examples: DMSO, DMF, acetone. Favors SN2 (Chs 10, 13).

Arene — Aromatic hydrocarbon ring (Ch 20).

Arenium ion — Cationic sp³ intermediate (cyclohexadienyl cation) in EAS; also called Wheland intermediate or σ-complex (Ch 21).

Aromatic — Cyclic, planar, conjugated, 4n+2 π electrons (Hückel rule, Ch 20).

Aryl — Group derived from an aromatic ring (e.g., phenyl, naphthyl). Often abbreviated Ar (Ch 20).

Asymmetric synthesis — Production of a single enantiomer (or one in large excess) from non-chiral or racemic starting materials (Chs 8, 16, 36).

Atactic — Polymer with random stereochemistry along the backbone; usually amorphous (Ch 37).

Atom economy — Mass fraction of starting-material atoms that appear in the product. Higher = greener (Ch 40).

Autoxidation — Spontaneous radical oxidation by O₂; responsible for rancid fats, polymer aging, lipid peroxidation (Ch 18).

Axial — In cyclohexane chair, bond perpendicular to the ring's mean plane. Large axial substituents suffer 1,3-diaxial strain (Ch 5).

Azide — -N₃. Nucleophile and explosive precursor; reduces to amine; click partner for alkynes (Chs 30, 40).

Azo — -N=N-. Chromophore in dyes (Ch 22).

Base (Brønsted, Lewis) — Proton acceptor (Brønsted) or electron-pair donor (Lewis) (Ch 3).

Beer-Lambert law — A = εcℓ. Quantitative basis for UV-Vis and colorimetric analysis (Ch 6).

Benzyl — The PhCH₂- group. Cation/radical resonance-stabilized into the ring (Ch 23).

Benzylic — Adjacent to aromatic ring. Cations and radicals resonance-stabilized (Ch 23).

Benzyne — 1,2-Didehydrobenzene; reactive triple-bond-in-a-ring intermediate. Roberts isotope experiment (Ch 23).

Biocatalysis — Use of enzymes (whole-cell or isolated) to catalyze synthetic reactions (Ch 40).

Biosynthesis — The pathway by which living systems assemble a molecule (Chs 28, 34).

Blocking group — Substituent installed temporarily to prevent reaction at one site; later removed (Chs 22, 31). Compare protecting group (which blocks a functional group, not a position).

Bond dissociation energy (BDE) — Energy to break bond homolytically. Table in Ch 2.

Bridgehead — Atom shared by two fused rings of a bicyclic system. Cannot bear a double bond in small rings (Bredt's rule) (Ch 5).

Bromonium ion — Three-member cyclic cation intermediate in Br₂ + alkene (Ch 15).

Brønsted acid/base — Proton donor/acceptor (Ch 3).

Brønsted plot — Linear free-energy plot of log k vs. pKa of catalyst; α/β slopes diagnose proton transfer in the TS (Ch 3).

Cage compound — Polycyclic molecule whose atoms enclose a cavity (e.g., adamantane, cubane) (Ch 5).

Cannizzaro — Base-induced disproportionation of an aldehyde lacking α-H into alcohol + carboxylate (Ch 25).

Carbanion — Carbon with three bonds, lone pair, formal charge -1. Strong base/nucleophile (Ch 27).

Carbene — Neutral C with 6 valence electrons (two bonds, two non-bonding electrons). Singlet or triplet. From diazo compounds (Chs 18, 37).

Carbocation — C with three bonds and formal +1 charge. Sp² planar. Key intermediate in SN1/E1 (Chs 11, 12). Classified by substitution: 1°, 2°, 3°, allyl, benzyl, vinyl (the last two are special cases — vinyl cations are very unstable; allyl/benzyl are resonance-stabilized).

Carbocation classification — 1° (one C neighbor, unstable), 2° (two), 3° (three, most stable); allyl/benzyl (resonance-stabilized, comparable to 3°); vinyl (sp, very unstable). Hyperconjugation explains the 1°<2°<3° ordering (Ch 11).

Carbonyl — C=O. Most important functional group in organic chemistry (Ch 24).

Carboxylate — R-CO₂⁻. Conjugate base of carboxylic acid; resonance-stabilized over both oxygens (Chs 3, 26).

Catalyst — Species that accelerates a reaction without being consumed; lowers E_a (Ch 5).

Catenane — Mechanically interlocked rings; topological isomer (Ch 40).

Cation — Positively charged species.

Chain reaction — Reaction propagated by an intermediate (often a radical) that is regenerated each turnover. Three stages: initiation, propagation, termination (Ch 18).

Charge-transfer complex — Loose donor-acceptor complex with absorption from HOMO(D) → LUMO(A) (Ch 19).

Chelate — Polydentate ligand that wraps a metal with multiple donor atoms (Ch 37).

Chemoselectivity — Preference for reacting one functional group while leaving another untouched (Chs 16, 36).

Chiral — Non-superimposable on its mirror image; lacks improper symmetry (S_n) (Ch 7).

Chiral auxiliary — Temporarily attached chiral group that biases stereochemistry in a subsequent step, then is removed (Chs 8, 38).

Chiral pool — The set of inexpensive, single-enantiomer natural products (amino acids, sugars, terpenes) used as starting materials (Chs 31, 38).

Chromatography — Separation by differential partitioning between stationary and mobile phases (TLC, column, HPLC, GC) (Ch 4 lab notes; see App J).

CIP rules — Cahn-Ingold-Prelog priority rules for assigning R/S and E/Z. Highest atomic number first; isotope ties break by mass (Ch 7).

Cis — Same-side substitution on a ring or double bond. Replaced in modern nomenclature by E/Z for alkenes (Ch 7).

Claisen condensation — Enolate + ester → β-keto ester + alkoxide LG (Ch 28).

Claisen rearrangement — [3,3]-sigmatropic shift of an allyl vinyl ether → γ,δ-unsaturated carbonyl (Ch 39).

Clemmensen / Wolff-Kishner — Reductions of C=O to CH₂ under acidic (Zn-Hg/HCl) and basic (H₂N-NH₂/KOH) conditions respectively (Ch 21).

Click chemistry — High-yielding, modular, wide-scope reactions (esp. CuAAC azide-alkyne cycloaddition) (Chs 39, 40).

Combinatorial chemistry — Parallel synthesis of large libraries for screening (Ch 35).

Common name vs IUPAC — Trivial names (acetone, formaldehyde, glycine) coexist with systematic IUPAC names (propan-2-one, methanal, 2-aminoethanoic acid). Both are acceptable in context (Ch 4).

Complexation — Formation of a non-covalent (often Lewis-acid/base) adduct.

Computational chemistry — Use of molecular orbital methods (DFT, HF, MP2) to predict structure, energies, mechanisms (Ch 2; see App E).

Condensation polymer — Polymer formed by step-growth with loss of small molecule (e.g., nylon, polyester) (Ch 26).

Configuration — 3D arrangement at a stereocenter; cannot be changed without bond breaking (Ch 7). Compare conformation.

Conformer — One of the energy minima accessible by rotation about single bonds (Ch 5).

Conjugate acid/base — Species formed by adding/losing H⁺ from a base/acid (Ch 3).

Conjugate (Michael) addition — 1,4-addition to α,β-unsaturated carbonyl (Ch 29).

Conjugation — Alternating single/double bonds with delocalized π electrons (Ch 19).

Contact ion pair — Cation and anion in immediate contact, still solvent-caged; intermediate in SN1 (Ch 11).

Coupling constant (J) — Distance in Hz between split NMR peaks; reports dihedral angle (Karplus) and connectivity (Ch 9).

Covalent inhibitor — Drug that forms a covalent bond to its target (e.g., aspirin → COX, ibrutinib → BTK) (Chs 26, 29, 35).

Crown ether — Cyclic polyether that binds cations selectively (18-crown-6 → K⁺) (Chs 10, 37).

Crystallization — Purification by selective deposition of crystals from solution (App J).

Dehydration — Loss of H₂O. Often E1 on alcohols with acid (Ch 12).

Dehydrogenation — Removal of H₂; reverse of hydrogenation (Ch 36).

Deprotonation — Removal of H⁺ by a base (Ch 3).

Delta G / ΔG — Gibbs free energy change. ΔG < 0 = thermodynamically favorable (Ch 5).

Deuterium (D, ²H) — Heavy-hydrogen isotope; used in mechanism (KIE) and NMR (solvent) (Chs 5, 9).

Dextrorotatory (+) — Rotates plane-polarized light clockwise (Ch 7).

Diastereomer — Stereoisomer that is NOT a mirror image (Ch 7).

Diastereoselectivity — Preference for forming one diastereomer over another (Ch 8).

Diazo — R₂C=N₂. Decomposes to give carbenes (Ch 37).

Diazonium — Ar-N₂⁺. Versatile aromatic intermediate; Sandmeyer, azo coupling (Chs 22, 30).

Dieckmann — Intramolecular Claisen → cyclic β-keto ester (Ch 28).

Diels-Alder — [4+2] cycloaddition of diene + dienophile (Ch 19).

Dienophile — Alkene/alkyne partner in Diels-Alder; usually electron-poor (Ch 19).

Diol — Dihydroxy compound. Vicinal diol (adjacent). Formed from alkene + OsO₄ (syn) or epoxide hydrolysis (anti) (Ch 16).

Dipole moment — Vector from δ+ to δ- end of polar molecule (Ch 2).

Directing group — Substituent that controls regiochemistry of attack (o/p- vs meta-directing in EAS; ortho-metalation directing groups in C-H activation) (Chs 22, 37).

Disconnection — In retrosynthesis, breaking a bond in the target to identify a known reaction that forms it (Chs 14, 31, 38; see App G).

Dispersion forces — Weak, transient induced-dipole/induced-dipole attractions; the only attractive force between hydrocarbons (Ch 5).

Distillation — Purification by selective vaporization. Fractional, vacuum, steam variants (Ch 5; App J).

Double bond — Two shared electron pairs (one σ, one π) (Ch 2).

Drug — A chemical that produces a biological effect of therapeutic intent (Ch 35).

Eclipsed — Conformer with substituents aligned at 0° dihedral; high torsional strain (Ch 5).

Electrocyclic reaction — Intramolecular pericyclic ring closing/opening of a conjugated π system (Ch 39).

Electrolysis — Driving non-spontaneous redox with applied potential; basis of synthetic electrochemistry (Ch 40).

Electron affinity — Energy released when a neutral atom gains an electron (Ch 2).

Electronegativity — Atom's pull on bonding electrons. Pauling scale (Ch 2).

Electrophile — Electron-poor species; attacks nucleophile (Ch 3).

Electrophilic — Adjective; electron-pair-accepting.

Electrospray (ESI) — Soft ionization for mass spec of large/polar/biomolecules (Ch 6).

Elimination — Loss of H and LG from adjacent carbons to form C=C (Chs 12, 16).

Enamine — R₂C=CR'-NR''₂. C-nucleophile (Stork enamine) (Ch 25).

Enantiomer — Non-superimposable mirror image (Ch 7).

Enantioselective — Preferring one enantiomer in product (Ch 8).

Enantiotopic — Two groups in a molecule that, when individually replaced, give enantiomers (Ch 7). NMR-equivalent in achiral solvent.

Enantiomeric excess (ee) — %major − %minor enantiomer. 0% = racemic; 100% = single enantiomer (Ch 7).

Endo (Diels-Alder) — Diastereomer with bulky/EWG substituents oriented under the diene; kinetic product (Ch 19).

Endothermic — ΔH > 0; absorbs heat (Ch 5).

Enol — C=C-OH tautomer of C-C-C=O (Ch 27).

Enol ether — Vinyl ether: C=C-OR (Ch 28).

Enolate — Deprotonated α-C of carbonyl (Ch 27).

Enthalpy (ΔH) — Heat at constant pressure; sum of bond energies (Ch 5).

Entropy (ΔS) — Measure of disorder; favored by gas formation, fragmentation, conformational freedom (Ch 5).

Enzyme — Biological catalyst (almost always a protein, sometimes RNA — ribozyme) (Ch 33).

Epimer — Diastereomer differing at exactly one stereocenter; common in sugars (Ch 32).

Epoxide — 3-membered ring with O. From mCPBA + alkene (Ch 16).

Equatorial — In cyclohexane chair, bond approximately in the ring's mean plane; less sterically strained than axial (Ch 5).

Equilibrium constant (K_eq) — Ratio of product/reactant activities at equilibrium; ΔG = -RT ln K (Ch 5).

Ester — R-CO₂-R' (Chs 24, 26).

Ether — R-O-R' (Ch 4).

Exo — In Diels-Alder, the diastereomer with bulky groups pointing away from the diene; thermodynamic product (Ch 19).

Exothermic — ΔH < 0; releases heat (Ch 5).

Felkin-Anh model — Predicts stereochemistry of Nu addition to a carbonyl with an adjacent stereocenter. Nu approaches opposite the largest substituent (Ch 8).

Fenton reaction — Fe(II) + H₂O₂ → Fe(III) + HO• + HO⁻. Generates damaging hydroxyl radicals (Ch 18).

FMO theory — Frontier molecular orbital theory; reaction outcomes predicted from HOMO-LUMO interactions (Chs 19, 39).

Fischer projection — Flat 2D representation of chiral center; horizontal = toward viewer (Ch 7).

Flash chromatography — Column chromatography with applied air pressure; standard prep method (App J).

Flow chemistry — Continuous-flow reactors instead of batch; improves heat/mass transfer and safety (Ch 40).

Fluorination — Installation of F; selective fluorination is a major topic in medchem (Chs 35, 40).

Formal charge — Bookkeeping: (valence e⁻) − (lone-pair e⁻) − (½ bond e⁻) (Ch 2).

Free energy — See Delta G.

Free radical — See radical.

Friedel-Crafts alkylation/acylation — EAS adding alkyl or acyl group; Lewis acid catalyst (Ch 21).

Frontier orbital — HOMO or LUMO (Chs 19, 39).

Functional group — Specific atom-grouping with characteristic reactivity (alcohols, ketones, amines, etc.) (Ch 4).

Geminal (gem) — On the same atom (e.g., gem-diol = C(OH)₂) (Ch 16).

Glycosidic bond — Acetal linkage between sugar units (Ch 32).

Green chemistry — Design of chemical processes to reduce/eliminate hazardous substances. Twelve principles (Anastas & Warner) (Ch 40).

Grignard reagent — R-MgX. C nucleophile. Adds to carbonyls (Ch 25).

Ground state — Lowest-energy electronic configuration (Ch 2).

Group transfer — Pericyclic reaction class involving migration of σ-bonded groups across π systems (Ch 39).

Half-life (t½) — Time for [reactant] to fall to half (Ch 5).

Haloform reaction — R-CO-CH₃ + 3 X₂/base → R-CO-CX₃ → R-COO⁻ + HCX₃ (Ch 27).

Halogen — F, Cl, Br, I.

Halohydrin — β-Halo alcohol; from alkene + X₂ in H₂O (Ch 16).

Hammond postulate — TS resembles whichever of R or P is closer to it in energy (Ch 5).

Hammett equation — log(k/k₀) = ρσ. Quantifies substituent electronic effects on rate/equilibrium (Ch 22).

Heat of combustion — ΔH for complete oxidation to CO₂ + H₂O; ranks alkene/alkane stability (Ch 5).

Heat of formation — ΔH_f° to form 1 mol of compound from elements in standard states (Ch 5).

Hemiacetal — R-CH(OH)(OR'). Intermediate in acetal formation (Ch 25).

Heteroatom — Any atom in an organic molecule other than C or H — typically N, O, S, P, halogen (Ch 4).

Heterocycle — Ring containing at least one heteroatom (pyridine, furan, indole) (Ch 20).

Heterolysis — Bond cleavage in which both electrons go to one atom; produces ions (Ch 3).

Hofmann rule — In E2 with bulky base, less-substituted alkene forms (Ch 12).

HOMO — Highest Occupied Molecular Orbital (Chs 2, 19).

Homologous series — Family differing by -CH₂- (e.g., alkanes) (Ch 4).

Homolysis — Bond cleavage in which each atom keeps one electron; produces radicals (Ch 18).

Hückel rule — Aromatic if 4n+2 π electrons in planar cyclic conjugated ring (Ch 20).

Hybridization — Mixing of s and p orbitals to give sp³, sp², sp (Ch 2).

Hydrate — Compound containing H₂O of crystallization; or gem-diol form of an aldehyde (Ch 25).

Hydration — Addition of H₂O across C=C or C=O (Chs 15, 16, 25).

Hydride — H with two electrons (H⁻); a 2-electron leaving group or migrating group (Ch 11).

Hydride shift — H migrates from adjacent C to carbocation with its electron pair (Ch 11).

Hydrocarbon — Compound of C and H only (Ch 5).

Hydrogenation — Addition of H₂ across a π bond; usually catalyzed by Pd, Pt, Ni (Chs 16, 36).

Hydrolysis — Cleavage of a bond by water; saponification = base-catalyzed ester hydrolysis (Ch 26).

Hydrophilic — Water-loving; polar/charged (Ch 4).

Hydrophobic — Water-fearing; nonpolar (Ch 4).

Hyperconjugation — σ bond donates into adjacent empty p orbital; stabilizes cations and explains Zaitsev (Chs 11, 12).

Imine — R₂C=NR' (Ch 25).

Inductive effect — Transmitted through σ bonds by electronegativity (Ch 3).

Infrared (IR) — Vibrational spectroscopy; identifies functional groups by C=O, O-H, N-H stretches (Ch 6).

Inhibitor — Substance that slows or stops a reaction; in pharmacology, blocks an enzyme (Ch 35).

Initiation — First step of a radical chain — generates the first radical (Ch 18).

Intermediate — Reactive species at an energy minimum between starting material and product; lives long enough to be observed in principle (Ch 5). Compare transition state.

Intramolecular — Within one molecule (vs intermolecular) (Ch 28).

Inversion (Walden) — SN2 stereochemistry — backside attack flips configuration (Ch 10).

Ionization — Removal/addition of electron; or solvolysis to ions (Ch 6).

Ionophore — Lipid-soluble molecule that transports ions across membranes; e.g., crown ethers, valinomycin (Ch 37).

Isoelectric point (pI) — pH of net zero charge for amino acid (Ch 33).

Isomer — Same molecular formula, different structure or arrangement.

Isotactic — Polymer with consistent stereochemistry along the backbone; usually crystalline (Ch 37).

Isotope — Same Z, different N; mass changes physical properties slightly (KIE, NMR shifts) (Ch 6).

Keto-enol tautomerism — Interconversion of keto and enol forms (Ch 27).

Ketone — R₂C=O (Chs 4, 24).

Kinetic control — Product distribution set by relative rates (lower-barrier path wins) (Chs 5, 19). Compare thermodynamic control.

Kinetics — Rate-dependent reaction behavior (Ch 5).

Lactam — Cyclic amide. β-lactam = penicillin core (Chs 26, 35).

Lactone — Cyclic ester (Ch 26).

Leaving group — Departs with bond electrons; good LG = low pKa conjugate acid (Chs 3, 10).

Levorotatory (−) — Rotates plane-polarized light counterclockwise (Ch 7).

Lewis acid/base — Electron-pair acceptor/donor (Ch 3).

Lewis structure — 2D drawing with all bonds and lone pairs (Ch 2).

Ligand — Donor group bound to a metal center (Ch 37).

Lindlar catalyst — Poisoned Pd (Pd/CaCO₃, Pb(OAc)₂, quinoline); reduces alkyne to cis-alkene (Ch 17).

Line-angle structure — Skeletal drawing — atoms at vertices, H implied (Ch 1).

Lipid — Hydrophobic biomolecule: fats, oils, phospholipids, steroids, terpenes (Ch 34).

LUMO — Lowest Unoccupied Molecular Orbital (Chs 2, 19).

Macrocycle — Ring of typically 12 or more atoms (Ch 37).

Magic acid — FSO₃H-SbF₅; superacid that protonates even alkanes; Olah (Ch 11).

Markovnikov rule — H adds to more-H-substituted C; X to other (alkene + HX, Ch 15). Modern statement: H goes where it gives the more stable carbocation.

Mass spectrum — Plot of m/z vs abundance; reveals molecular formula and fragmentation pattern (Ch 6).

McLafferty rearrangement — γ-H transfer through 6-membered TS in MS fragmentation of carbonyls (Ch 6).

Mechanism — Step-by-step electron movement showing how reactants become products (Ch 3).

Meinwald rearrangement — Lewis-acid-catalyzed epoxide-to-aldehyde isomerization (Ch 16).

Meisenheimer complex — Anionic intermediate in SNAr (Ch 23).

Meso — Molecule with stereocenters but internal mirror plane; achiral (Ch 7).

Mesomeric effect — Resonance/π-donating or -withdrawing effect of a substituent (Ch 22).

Metal-catalyzed — Reaction in which a transition-metal complex mediates bond making/breaking (Ch 37).

Methylene — -CH₂- group; or :CH₂ carbene (Ch 37).

Micelle — Spherical surfactant aggregate with hydrophobic core and hydrophilic surface (Ch 34).

Michael acceptor/donor — α,β-Unsaturated carbonyl (acceptor); enolate (donor) (Ch 29).

Migration — Movement of a group with its bonding electrons (hydride or alkyl shift) (Ch 11).

Molecular orbital (MO) — Wavefunction describing electrons delocalized over a molecule (Ch 2).

Monomer — Single repeating unit of a polymer (Ch 37).

Multiplicity — In NMR, splitting pattern (singlet, doublet, triplet...); n+1 rule (Ch 9).

Mutarotation — Interconversion of α/β anomers via open chain (Ch 32).

Neighboring group participation (NGP) — See anchimeric assistance (Ch 11).

Newman projection — View down C-C axis with front C (dot) and back C (circle) (Ch 5).

NIH shift — 1,2-Hydrogen migration during cytochrome P450 arene hydroxylation (Ch 36).

Nitrile — R-C≡N (Ch 24).

Nitrene — Neutral N with 6 valence electrons; R-N: (Ch 30).

Nitrile oxide — R-C≡N⁺-O⁻; 1,3-dipole (Ch 39).

Nitro — -NO₂. Strong EWG; meta-director; precursor to amines by reduction (Chs 21, 22).

Nitroso — -N=O. Intermediate in NO biochemistry (Ch 18).

NMR active nuclei — Nuclei with I ≠ 0: ¹H, ¹³C, ¹⁵N, ¹⁹F, ³¹P. ¹²C and ¹⁶O are NMR silent (Ch 9).

Nuclear Overhauser effect (NOE) — Through-space dipolar coupling; reveals atoms within ~5 Å (Ch 9).

Nucleofuge — Synonym for leaving group; emphasizes the LG side of the SN reaction (Ch 10).

Nucleophile — Electron-rich species; attacks electrophile (Ch 3).

Nucleotide — Phosphate ester of nucleoside; building block of DNA/RNA (Ch 33).

Octet rule — Second-row atoms tend toward 8 valence electrons (Ch 2).

Optical activity — Rotation of plane-polarized light by a chiral substance (Ch 7).

Optically active — Exhibits optical activity; chiral and not racemic (Ch 7).

Orbital — One-electron wavefunction; s, p, d... atomic, or σ, π... molecular (Ch 2).

Organometallic — Compound with metal-carbon bond (Grignards, organolithiums, Pd-aryl) (Chs 25, 37).

Ortho/para/meta-directing — Positional effect of substituent in EAS (Ch 22).

Oxidation — Increase in oxidation state (or bonds to O, N, X) (Ch 36).

Oxidation state — Hypothetical charge if all bonds were ionic (Ch 36).

Oxidative addition (OA) — A 2-electron oxidation of a metal as it inserts into an X-Y σ bond (Ch 37).

Oxime — R₂C=N-OH (Ch 25).

Ozonide — Cyclic O₃ adduct of alkene; cleaved by Zn/H₂O or Me₂S to carbonyls (Ch 16).

Palladium (Pd) — Most important transition metal for cross-coupling (Suzuki, Heck, Negishi, Sonogashira, Buchwald-Hartwig) (Ch 37).

Parent chain — Longest continuous C chain (or smallest ring) chosen in IUPAC naming (Ch 4).

Peptide bond — Amide between α-COOH and α-NH₂ of two amino acids (Ch 33).

Pericyclic — Concerted reactions with cyclic TS (Ch 39).

pH — −log₁₀[H₃O⁺] (Ch 3).

Phase-transfer catalyst (PTC) — Quaternary ammonium or crown ether that shuttles ions between aqueous and organic phases (Ch 10).

Phenoxide — Conjugate base of phenol; resonance-delocalized into ring (Chs 3, 22).

Phenyl (Ph) — C₆H₅- group (Ch 20).

Phosphine — R₃P. Donor ligand in transition-metal catalysis; nucleophile (Wittig) (Chs 25, 37).

Photochemistry — Chemistry driven by absorption of light; flips selection rules vs thermal (Ch 39).

Pi (π) bond — Bond from side-by-side overlap of p orbitals (Ch 2).

π-system — Set of conjugated p orbitals.

pKa — Negative log of acid dissociation constant; quantitative acidity (Ch 3).

Polar solvent — High dielectric constant; can be protic (MeOH, H₂O) or aprotic (DMSO, DMF) (Ch 10).

Polarimeter — Instrument that measures optical rotation (Ch 7).

Polarizability — Ease of electron-cloud distortion; large/heavy atoms more polarizable (Ch 10).

Polymer — Macromolecule built from many monomer units (Chs 26, 37).

Polymorphism — Different crystal forms of the same compound (Ch 35).

Post-translational modification (PTM) — Covalent change to a protein after synthesis (phosphorylation, glycosylation, ubiquitination) (Ch 33).

Prochirality — A non-chiral center that becomes chiral on differentiation of one ligand (Ch 8).

Propagation — Self-sustaining step(s) of a chain reaction (Ch 18).

Protecting group — Temporarily masks reactive functionality during synthesis (Ch 31).

Protic solvent — Solvent with -OH/-NH/-SH (H-bond donor) (Ch 10).

Prototropy — Tautomerism specifically involving H migration (Ch 27).

Pseudoasymmetric — Stereocenter whose four ligands include a pair of enantiomers; uses lowercase r/s (Ch 7).

Purification — Separation of product from impurities (recrystallization, distillation, chromatography) (App J).

Pyranose — 6-member cyclic form of sugar (Ch 32).

Pyrolysis — Thermal decomposition (Ch 18).

Racemate — Equal mixture of enantiomers; no optical rotation (Ch 7).

Racemization — Process by which an enantiopure sample becomes racemic (Ch 8).

Radical — Species with unpaired electron (Ch 18).

Radical cation — Species with both unpaired electron and + charge; common in mass spectrometry (Ch 6).

Rate-determining step (RDS) — Slowest step; gates the overall rate (Ch 5).

Recrystallization — Purification by selective crystallization from a hot solvent on cooling (App J).

Reduction — Decrease in oxidation state (or bonds to H gained, bonds to O/N/X lost) (Ch 36).

Reductive amination — Carbonyl + amine + NaBH(OAc)₃ → amine (Ch 30).

Reductive elimination (RE) — Loss of two ligands from a metal as a new C-C, C-H, or C-X bond, with 2-electron reduction of the metal (Ch 37).

Reflux — Heating with continuous condensation back into the flask (App J).

Regiochemistry — Which atom of a reagent attacks which atom of the substrate (Markovnikov, ortho/para, etc.). Compare: Stereochemistry = 3D outcome; regio = which-atom-where. The two are independent (Ch 15).

Regioselective — Preferentially gives one regioisomer (Ch 15).

Resolution (of enantiomers) — Separation of a racemate into its enantiomers, typically by forming diastereomeric salts (Ch 7).

Resonance — Delocalization of electrons among contributing structures (Ch 2).

Retrosynthetic analysis — Working backward from target to precursors (Chs 14, 31; App G).

Ribozyme — Catalytic RNA (Ch 33).

Ring contraction — Rearrangement that yields a smaller ring (Wolff, Favorskii) (Ch 27).

Ring expansion — Rearrangement that yields a larger ring (semi-pinacol, Tiffeneau-Demjanov) (Ch 11).

Ring opening — Cleavage of a ring (epoxide opening, retro-Diels-Alder) (Ch 16).

Ring strain — Energy cost of ring geometry (angle, torsional, transannular). Cyclopropane and cyclobutane are strained; cyclohexane is not (Ch 5).

Robinson annulation — Michael + aldol condensation → 6-ring enone (Ch 29).

Rotamer — Conformer interconvertible by simple rotation (Ch 5).

S character — Fraction of s orbital in a hybrid; sp = 50%, sp² = 33%, sp³ = 25%. More s = shorter, stronger, more acidic C-H (Chs 2, 17).

Saponification — Base-mediated hydrolysis of an ester (soap-making) (Ch 26).

Sawhorse projection — Tilted-perspective view of a C-C bond (Ch 5).

Schlenk technique — Air- and moisture-free manipulation using inert gas (App J).

Secondary (2°) — Carbon bearing two C neighbors; also classification of amines, alcohols, halides (Ch 4).

Sigma (σ) bond — Bond from head-on orbital overlap (Ch 2).

Sigmatropic rearrangement — σ bond migrates across a π system; numbered [i,j] (Cope = [3,3], Claisen = [3,3]) (Ch 39).

Silyl ether — R-O-SiR'₃; TMS, TBS, TIPS, TBDPS protecting groups (Ch 31).

Single bond — One shared electron pair; pure σ (Ch 2).

Singlet — Spin-paired excited state; in carbenes, lone pair in sp² + empty p (Ch 39).

SN1 — Substitution, unimolecular, via carbocation; racemization (Ch 11).

SN2 — Substitution, bimolecular, concerted, backside attack; inversion (Ch 10).

SNAr — Nucleophilic aromatic substitution; requires activating EWG (Ch 23).

Solvolysis — SN1/E1 with the solvent acting as the nucleophile/base (Ch 11).

sp/sp²/sp³ — Hybridizations giving tetrahedral/trigonal/linear geometries (Ch 2).

Specific rotation [α] — Optical rotation normalized to concentration and path length (Ch 7).

Spectroscopy — Probing molecules with electromagnetic radiation (IR, NMR, UV-Vis, MS) (Chs 6, 9).

Spiro — Two rings sharing exactly one atom (Ch 5).

Staggered — Conformer with substituents at 60°; minimum torsional strain (Ch 5).

Stereocenter — Atom whose 3D arrangement is a source of stereoisomerism (usually sp³ C with 4 different groups) (Ch 7).

Stereogenic — Synonym for stereocenter; broader (includes axes, planes) (Ch 7).

Stereoselective — Preferring one stereoisomer of a possible set (Ch 8). Compare stereospecific.

Stereospecific — Each stereoisomer of starting material gives a different specific stereoisomer of product (a stronger requirement than stereoselective) (Ch 8).

Steric — Spatial; relating to size and shape of groups (Ch 5).

Steric strain — Energy cost of two non-bonded atoms being too close (Ch 5).

Strecker synthesis — Aldehyde + NH₃ + HCN → α-aminonitrile → α-amino acid (Ch 33).

Substituent — Group replacing H on a parent chain (Ch 4).

Substrate — Starting material acted upon by reagents/catalyst (Ch 10).

Suprafacial — Same-face attack on a π system in a pericyclic reaction (Ch 39).

Syn/anti addition — Both new groups on same face (syn) or opposite (anti) (Chs 8, 16).

Syndiotactic — Polymer with alternating stereochemistry (Ch 37).

Synthesis — Construction of a target molecule from simpler precursors (Chs 14, 31, 38).

Synthon — Idealized fragment representing one half of a retrosynthetic disconnection (e.g., R-CO⁺ or R⁻) (App G).

Tautomer — Isomers differing by placement of one H + double bond (Ch 27).

Terpene — Isoprene-derived natural product; classified by C-count (mono- C₁₀, sesqui- C₁₅, di- C₂₀, tri- C₃₀) (Ch 34).

Tertiary (3°) — Carbon bearing three C neighbors; also classification of amines, alcohols, halides (Ch 4).

Tetrahedral — Four bonds at 109.5°; sp³ geometry (Ch 2).

Tetrahedral intermediate — Sp³ intermediate in addition/acyl substitution (Chs 25, 26).

Tetrasubstituted — Bearing four non-H substituents (most stable alkene class) (Ch 15).

Thermodynamic control — Product set by relative stability (Chs 5, 19). Compare kinetic control.

Thermolysis — Thermal decomposition (Ch 18).

Thiol — R-SH. More acidic, more nucleophilic, more polarizable than alcohol (Ch 4).

Tosylate — R-OTs. Excellent leaving group (Ch 10).

Trans — Opposite-side substitution on a ring or double bond (Ch 7).

Transesterification — Exchange of ester -OR with -OR'; acid- or base-catalyzed (Ch 26).

Transition metal — d-block element; central to organometallic and biocatalysis (Ch 37).

Transition state (TS) — Highest-energy point on the reaction coordinate; no lifetime (Ch 5).

Tridentate — Ligand donating through three atoms (Ch 37).

Triplet — Spin-parallel excited state; in carbenes, two singly-occupied orbitals (Ch 39). In NMR, a 1:2:1 splitting pattern.

Triple bond — Three shared electron pairs (1 σ + 2 π) (Ch 17).

Umpolung — Polarity reversal — making a normally electrophilic atom nucleophilic (e.g., dithiane acyl anion equivalents) (Ch 27).

Unsaturation, degrees of (DoU) — (2C+2+N−H−X)/2; sum of rings + π bonds (Ch 6).

Valence — Number of bonds an atom forms in its neutral state (Ch 2).

Van der Waals — Generic term for weak intermolecular forces (London, dipole-dipole) (Ch 5).

Vicinal (vic) — On adjacent carbons (e.g., vicinal diol) (Ch 16).

Vinyl — -CH=CH₂ group; or anything attached to sp² C of an alkene (Ch 15).

Walden inversion — Stereochemistry inversion in SN2 (Ch 10).

Williamson ether synthesis — Alkoxide + alkyl halide → ether (Ch 10).

Wittig reaction — Ph₃P=CR₂ + carbonyl → alkene + Ph₃PO (Ch 25).

Woodward-Hoffmann rules — Orbital symmetry rules for pericyclic reactions (Chs 19, 39).

Working-up (work-up) — Post-reaction quench, wash, dry, concentrate. The unglamorous half of every experiment (App J).

Yield — Mol product / mol limiting reagent × 100%. Isolated yield ≠ NMR yield (App J).

Z (alkene geometry) — Higher-priority groups on same side (CIP) (Ch 7). Compare E (opposite sides).

Zaitsev rule — Most-substituted alkene preferred in E2 (Ch 12).

Zwitterion — Molecule with both + and − charges; net zero charge (Ch 33).

Commonly confused pairs

• Configuration vs. conformation — Configuration is set by bonding (changing it requires breaking a bond). Conformation is set by rotation around single bonds (free to interconvert at room temp).
• Regiochemistry vs. stereochemistry — Regio = which-atom-where (Markovnikov, ortho/para). Stereo = 3D arrangement (R/S, cis/trans, endo/exo).
• Stereoselective vs. stereospecific — Selective = preferential; specific = mandated by mechanism. Every stereospecific reaction is stereoselective; the reverse is not true.
• Kinetic vs. thermodynamic control — Kinetic = fastest path wins; thermodynamic = most stable wins.
• Inductive vs. resonance — Inductive = through-σ-bond electron pull; resonance/mesomeric = through-π-bond delocalization. Often act together; sometimes opposite (halogens are σ-EW but π-donating).
• Homolysis vs. heterolysis — Homolysis splits a bond evenly into two radicals; heterolysis splits it ionically.
• Enantiomer vs. diastereomer — Enantiomers are mirror images (all stereocenters inverted); diastereomers are non-mirror stereoisomers (some inverted, not all).
• Hemiacetal vs. acetal — Hemi has one OR + one OH; full acetal has two OR (no OH). Hemiacetal is intermediate, acetal is product.
• Protecting group vs. blocking group — Protecting group masks a functional group; blocking group occupies a ring position. Both later removed.

~370 terms cross-referenced to chapters. Reference while reading; do not memorize.