Synopsis of SN1, SN2, E1 and E2 Reactions

Subsitution Nucleophilic Unimolecular (SN1) Subsitution Nucleophilic Bimolecular (SN2) Rate = k [RX] Rate = k [RX] [Nuc] Kinetics Only substrate (RX) involved in rate- Rate-determining step involves both substrate and determining step (slow step). nucleophile Weak nucleophiles (i.e. neutral); on periodic Strong nucleophile - negatively charged better (eg. Nucleophile table: nucleophile increases strength going to methoxide better than methanol). the left and going down Relatively uninhindered alkyl halide; methyl>1˚>2˚. Substrates that form relatively stable Due to steric hinderence, 3˚ virtually unreactive by S 2 Substrate Reactivity carbocations; 3˚>2˚>>1˚>methyl N (in the presence of good nucleophile/base it undergoes (1˚ & methyl virtually unreactive by S 1) N E2) Stereochemistry Results in racemization. always inversion of configuration Occurs if more stable carbocation can form (eg. Rearrangements Do not occur 2˚ to 3˚) Solvents that leave nucleophile (anion) relatively Highly ionizing solvents; polar, protic favored unencumbered. Theoretically, apolar solvents are the Solvents (eg. water, methanol, ethanol, alcohol, best but, in practice, a polar aprotic (eg. DMF, DMSO, ammonia) THF) is necessary to help dissolve the nucleophile. Occurs in several steps, the rate-determining One-step mechanism; no intermediates; transition state Reaction Mechanism step is the unimolecular ionization of the involves both nucleophile and substrate (bimolecular) substrate to form a carbocation intermediate In the TS, R takes on δ+ (leading to Nucleophile displaces leaving group. Both incoming Transition State (TS) carbocation) and X takes on δ- (leading to nucleophile (Nuc-) and exiting leaving group (X-) bear a leaving group) δ- charge in the TS. Leaving group Good leaving group Good leaving group

Elimination Unimolecular (E1) Elimination Bimolecular (E2) Rate = k [RX] Rate = k [RX] [Nuc] Kinetics Only substrate (RX) involved in rate- Rate-determining step involves both substrate and base determining step (slow step). - Since the reaction rate depends only on [RX], Strong, slightly polarizable base (amide ion NH2 or Base and Nucleophile the base doesn’t matter. However, a strong alkoxide ion); strong sterically hindered base; (a weakly Charactersitics base may lead to elimination by the E2 basic ion or a weakly basic & highly polarizable ion mechanism. increases the likelihood of SN2 ) + Substrate Reactivity 3˚ > 2˚ (1˚ & CH3 do not undergo E1) 3˚ > 2˚ > 1˚ with strong base (eg. ethoxide ion) Carbocations may rearrange to a more stable Rearrangements Do not occur one (eg. 2˚ to 3˚) Zaitsev’s Rule: If 2 or more alkenes products are possible, the reaction will favor the production of the Products Conforms to Zaitsev’s Rule (see right) more highly-substituted alkene (more stable). Hoffman’s Rule: Less substituted alkene is the major product (tertiary butoxide is often used in these cases)

Solvent Same as SN1 Similar to SN2 Occurs in several steps, the rate-determining Reaction Mechanism step is the unimolecular ionization of the As in SN2 reaction, there are no intermediates. substrate to form a carbocation intermediate Higher temps increase the amount of E1 over ‡ SN1. Although E1 has a higher ∆G , the Temperature increased kinetic energy of molecules at higher High temps give increased E2 product (see left) temps make them less sensitive to the difference in TS energies of E1 and SN1.

B - The TS must be Transition State (TS) Rate limiting TS same as in SN1. anti-periplanar H

X