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)
Substrate: Sterics
(methyl > 1° > 2°) No SN2 with 3°! Orbital Overlap (methyl ≅ benzylic > allylic > 1°)
Elimination Reactions: E2 versus E1
Substrate: Alkene Stability
(3° > 2° > 1°)
Loss of Stereochemistry
Cation Stability (benzylic > allylic > 3° > 2°) No 1° or methyl R+ without extra stabilization!
Nucleophile: Strong/Moderate Required
Not Important strong: RS–, I–, R2N–, R2NH, RO–, CN–
moderate: RSH, Br–, RCO2–
Leaving Group: Moderately Important
(same trend as SN1)
Very Important (–OTf >> –OTs ≅ –OMs >> –I > –Br > –Cl)
Solvent: Polar Aprotic Polar Protic
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
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).
Cation Stability (benzylic > allylic > 3° > 2°)
Base: Strong Base Required
Not Important: Usually Weak (RO–, R2N–)
(ROH, R2NH)
Leaving Group: Moderately Important
(same trend as SN1)
Very Important (same trend as SN1)
Solvent: Wide Range of Solvents Polar Protic
1
Generic Reaction-Energy Diagrams
Substitution Elimination
‡
R‡ ‡ R
RX − ‡
δ
− +
δ Nuc δ
δ R ygren y
X − R R HR e
gren δ−
e B R X Nuc–
RR Nuc
X–
X
R
B–

RR
RR
R

BH
R

reaction coordinate (SN2)

reaction coordinate (E2) Bimolecular
‡‡

Unimolecular
CHR2
‡
‡
−
δ X
R
+
δ
‡ RDS
−
δ
R Nuc
+ R
δ R
‡
R
R
−
δ X
+
δ
‡ RDS
R
R +
δ
R

R
R
‡
Hδ−
y gren
eR X Nuc–
R XNuc
–

reaction coordinate (SN1)

Predicting the Products: Substitution versus Elimination
no
Is Nuc/Base strong?
Unimolecular Reaction RR
B
R+NucX–
–y

gren
eR R
X–

X
R B–RR
B–

RR
RR
R

BH
R reaction coordinate (E1)
Start

Bimolecular
yes Reaction
Is Nuc/Base bulky?
E2
* Under conditions that favor a unimolecular reaction (weak nuc/base and polar protic solvent), mixtures of SN1 and E1 are usually obtained.
What kind of substrate?
1°
2°, 3°, or stabilized 1°

SN2 + E2
Unfavorable yes
Reaction
no
What kind of substrate?
methyl or 1°

SN2

3° mostly E1*
yes Is Nuc/Base bulky? 2°
no

mostly SN1*
2