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
(inversion)
Loss of Stereochemistry
Substrate:
Sterics
(methyl > 1° > 2°)
No SN2 with 3°!
Orbital Overlap
(methyl ≅ benzylic > allylic > 1°)
Cation Stability
(benzylic > allylic > 3° > 2°)
No 1° or methyl R+
without extra stabilization!
Nucleophile:
Strong/Moderate Required
strong: RS–, I–, R2N–, R2NH, RO–, CN–
moderate: RSH, Br–, RCO2–
Not Important
Leaving Group:
Moderately Important
(same trend as SN1)
Very Important
(–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
(antiperiplanar TS)
Not Stereospecific
Substrate:
Alkene Stability
(3° > 2° > 1°)
Cation Stability
(benzylic > allylic > 3° > 2°)
Base:
Strong Base Required
(RO–, R2N–)
Not Important: Usually Weak
(ROH, R2NH)
Leaving Group:
Moderately Important
(same trend as SN1)
Very Important
(same trend as SN1)
Wide Range of Solvents
Polar Protic
Solvent:
Product Ratio:
Saytzeff Rule: The most highly substituted alkene usually predominates.
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
‡
R
δ−
δ+
Nuc
δ−
X
RR
‡
X
δ−
B
energy
energy
‡
RR
H
R R
δ−
R
R X
Nuc–
X B–
R
R
R R
R Nuc
X–
R
R
B H
R
reaction coordinate (SN2)
reaction coordinate (E2)
Bimolecular
δ−
X
R
δ+
‡
RR
R
δ−
‡ RDS
‡
Unimolecular
Nuc
CHR2
δ−
δ+
X
δ+
RR
‡ RDS
‡
RR
RR
‡
‡
B
R X–
R
energy
energy
‡
R
R
H
δ−
R
R+ X–
Nuc–
δ+
R
B–
R
R X
Nuc–
X B–
R
R
R R
R
R
R Nuc
X–
reaction coordinate (SN1)
B H
R
reaction coordinate (E1)
Predicting the Products: Substitution versus Elimination
Start
Bimolecular
Reaction
yes
Is Nuc/Base strong?
no
What kind of substrate?
1°
Is Nuc/Base bulky?
2°, 3°, or
stabilized 1°
Unfavorable
Reaction
yes
Unimolecular
Reaction
E2
no
3°
mostly E1*
What kind of substrate?
yes
Is Nuc/Base bulky?
2°
methyl or 1°
SN2
SN2 + E2
no
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