Organic chemistry tricks that make reaction mechanisms stick

SN2 requires: strong nucleophile (OH⁻, CN⁻, I⁻), primary (or methyl) substrate, polar aprotic solvent. One step — backside attack causes Walden inversion. Rate = k[substrate][nucleophile].

SN1 requires: stable carbocation intermediate, tertiary (or secondary) substrate, polar protic solvent (water, alcohol). Two steps. Racemization occurs. Rate = k[substrate] only.

E2: strong bulky base, heat, one concerted step. Requires anti-periplanar geometry (H and LG 180° apart). Follows Zaitsev's rule — most substituted alkene is major product.

Strong nucleophile + primary = SN2. Strong base + heat = E2. Tertiary + weak nucleophile/base = SN1/E1. Polar protic solvent favors SN1/E1. Polar aprotic favors SN2.

Curved arrows show electron movement — always from electron-rich to electron-poor. Tail at electron source (lone pair or bond). Head at destination. Never draw arrows backwards.

Free radicals (one unpaired electron) follow the same stability order as carbocations: tertiary > secondary > primary > methyl. Alkyl groups stabilize radicals by hyperconjugation (C-H bonds donate into singly occupied orbital). Allylic and benzylic radicals are especially stable (resonance delocalization). Vinyl and aryl radicals are unstable. Stability determines selectivity in radical reactions (Br• is selective — attacks most stable radical).

Carbocations rearrange to more stable structures. Hydride shift: H (with its bonding electrons) migrates from adjacent carbon → new carbocation on original carbon. Methyl shift: CH₃ migrates similarly. Both are 1,2-shifts (to adjacent carbon). Rearrangements occur when: (1) a less stable carbocation can become more stable, (2) a ring can expand or contract to more stable system. Predict rearrangements on every SN1 or electrophilic addition question — always ask: could this carbocation rearrange?

Pericyclic reactions occur through a cyclic transition state with no intermediates — electrons reorganize simultaneously. Types: Cycloadditions (Diels-Alder [4+2], [2+2]). Electrocyclic reactions (ring opening/closing). Sigmatropic rearrangements (Cope, Claisen). Governed by Woodward-Hoffmann rules: thermal [4+2] allowed; thermal [2+2] forbidden (photochemical). The key: count electrons in the transition state and determine if orbital symmetry is conserved.

Acid-base reactions go to the side with the WEAKER acid (lower pKa = stronger acid). Rule: proton transfers from stronger acid to stronger base → gives weaker acid and weaker base. To determine if a reaction proceeds: compare pKa of reactant acid vs product acid. If product acid has higher pKa → reaction is favorable (Keq > 1). Example: H₂O (pKa 15.7) + NaH → NaOH (pKa 15.7 on product side). Actually pKa of H₂ ~35, so NaH deprotonates water completely.

FMO theory explains reactivity using the HOMO (highest occupied MO) of nucleophile and LUMO (lowest unoccupied MO) of electrophile. Nucleophile HOMO donates into electrophile LUMO. The orbital energy gap determines reactivity. In pericyclic reactions: thermal reactions require HOMO of one component to overlap with LUMO of the other in a thermally-allowed sense. This explains why Diels-Alder is thermally allowed ([4π+2π]) and [2+2] is not.

Br₂ or Cl₂ adds across alkene with ANTI stereochemistry (bromine atoms end up on opposite faces). Mechanism: Br₂ approaches pi bond → forms bromonium ion (3-membered ring, Br⁺ bridges two carbons) → Br⁻ attacks the back face (SN2) at more substituted carbon → anti-addition product. Result: trans-dibromide from cyclic alkenes. Proof of bromonium ion: meso product from cis-alkene, rac mixture from trans-alkene.

Polar protic solvents (water, alcohols, acetic acid) stabilize both cations and anions through hydrogen bonding and solvation. Favor SN1 (stabilize carbocation), disfavor SN2 (solvate nucleophile, reducing its reactivity). Polar aprotic solvents (DMSO, DMF, acetone, acetonitrile) do NOT hydrogen bond — anions are 'naked' and highly reactive. Strongly favor SN2. Non-polar solvents (hexane, benzene) are used for radical reactions and reactions needing no ionic intermediates.

An internal nucleophile (group within the molecule) can assist ionization of a leaving group — forms a cyclic intermediate. Results in: (1) anchimeric assistance (rate acceleration), (2) unexpected stereochemistry (retention instead of inversion). Example: a threo-beta-bromo sulfide undergoes solvolysis with retention (sulfur internally attacks → sulfonium ion → opened by external nucleophile from both faces). Recognize: retention of configuration or rearrangement often signals neighboring group participation.