Predict S_N1, S_N2, E1, E2

Consider three factors: substrate structure (methyl, primary, secondary, or tertiary), nucleophile/base strength and size, and solvent (polar protic vs polar aprotic). Strong nucleophiles favor substitution on unhindered substrates (SN2), strong bulky bases favor elimination (E2), and weak nucleophiles with tertiary substrates in protic solvents favor SN1/E1.

SN2 is a one-step mechanism where the nucleophile attacks as the leaving group departs. It requires backside attack, works best on unhindered substrates, and inverts stereochemistry. SN1 is a two-step mechanism: the leaving group departs first to form a carbocation, then the nucleophile attacks. It favors tertiary substrates and produces racemic products.

E2 is concerted: a base abstracts a beta-hydrogen anti-periplanar to the leaving group, forming the double bond in one step. It requires a strong base. E1 is stepwise: the leaving group departs to form a carbocation, then a beta-hydrogen is lost. E1 competes with SN1 since both share the same carbocation intermediate.

SN2 requires backside attack on the carbon bearing the leaving group. On a tertiary carbon, three bulky alkyl groups block the back side, making the transition state too crowded. Instead, tertiary substrates react via SN1/E1 (carbocation) or E2 (base abstracts beta-H).

Zaitsev's rule states that elimination preferentially forms the more substituted (more stable) alkene. This is the major product with most bases. However, bulky bases like potassium tert-butoxide favor the less substituted (Hofmann) product because steric hindrance prevents them from reaching the more hindered beta-hydrogen.

Polar protic solvents (water, alcohols) stabilize carbocations and favor SN1/E1 pathways. They also solvate nucleophiles, slowing SN2. Polar aprotic solvents (DMSO, DMF, acetone) leave nucleophiles unsolvated and more reactive, favoring SN2.