Chemistry 5.12 Spring 2003, Handout #9 Substitution Reactions (SN2 versus SN1)

SN2 SN1

Mechanism: Concerted Two Steps (Look for carbocation rearrangements.)

Rate Equation: Rate = kr[R–X][Nuc] Rate = kr[R–X]

Stereochemistry: Stereospecific Loss of Stereochemistry (inversion)

Substrate: Sterics Cation Stability (methyl > 1° > 2°) (benzylic > allylic > 3° > 2°) + No SN2 with 3°! No 1° or methyl R Orbital Overlap without extra stabilization! (methyl @ benzylic > allylic > 1°)

Nucleophile: Strong/Moderate Required Not Important – – – – – strong: RS , I , R2N , R2NH, RO , CN – – moderate: RSH, Br , RCO2

Leaving Group: Moderately Important Very Important (–OTf >> –OTs @ –OMs >> (same trend as SN1) –I > –Br > –Cl)

Solvent: Polar Aprotic Polar Protic

Elimination Reactions: E2 versus E1

E2 E1

Mechanism: Concerted Two Steps (Look for carbocation rearrangements.)

Rate Equation: Rate = kr[R–X][Base] Rate = kr[R–X]

Stereochemistry: Stereospecific Not Stereospecific (antiperiplanar TS)

Substrate: Alkene Stability Cation Stability (3° > 2° > 1°) (benzylic > allylic > 3° > 2°)

Base: Strong Base Required Not Important: Usually Weak – – (ROH, R NH) (RO , R2N ) 2

Leaving Group: Moderately Important Very Important

(same trend as SN1) (same trend as SN1)

Solvent: Wide Range of Solvents Polar Protic

Saytzeff Rule: The most highly substituted alkene usually predominates. Product Ratio: Hofmann Product: Use of a sterically hindered base will result in formation of the least substituted alkene (Hofmann product).

1 Generic Reaction-Energy Diagrams Substitution Elimination

‡ d- ‡ R X ‡ R ‡ R d- d+ d- Nuc X R H R R R d- B energy energy

R R X X – Nuc– R B R R R R Nuc R B H X– R R

reaction coordinate (SN2) reaction coordinate (E2) Bimolecular Unimolecular ‡ ‡ ‡ ‡ CHR R + - 2 R d R - R d d+ ‡ RDS R d- d X d+ ‡ RDS d+ R X Nuc R ‡ R H RR ‡ RR d- B R

+ – R X– R X R – B– Nuc R energy energy

R

X – R X R B – R Nuc R R R R Nuc R B H X– R

reaction coordinate (SN1) reaction coordinate (E1)

Predicting the Products: Substitution versus Elimination Start

Bimolecular yes no Is Nuc/Base strong? Reaction What kind of substrate? 1° 2°, 3°, or stabilized 1° Unfavorable Is Nuc/Base bulky? yes Reaction Unimolecular Reaction no E2

3° yes What kind of substrate? mostly E1* Is Nuc/Base bulky? 2°

methyl or 1° SN2 + E2 no

SN2 mostly SN1*

* Under conditions that favor a unimolecular reaction (weak nuc/base and polar protic solvent),

mixtures of SN1 and E1 are usually obtained.

2