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

(same trend as SN1) (–OTf >> –OTs ≅ –OMs >>
–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

(RO–, R2N–) (ROH, R2NH)

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
‡
δ−
‡ X
‡ R ‡ RR
δ− δ+ δ−
Nuc X
H RR
R R
δ−
B
energy

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

reaction coordinate (SN2) reaction coordinate (E2)

Bimolecular
‡ ‡
Unimolecular CHR2
‡ ‡
RR δ+
R δ− R δ− δ+ ‡ RDS R
δ− ‡ RDS X
X δ+ Nuc δ+ R
RR ‡
H
RR ‡ RR
δ−
B
R
R X–
R+ X– R
energy

energy
Nuc– R
B–

R
X B–
R X R
R
Nuc– R R
R
R B H
R Nuc
X– R
reaction coordinate (SN1) reaction coordinate (E1)

Predicting the Products: Substitution versus Elimination

Start

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