I Br Cl CN SH SR N C CR OH OR NH

Lecture Summary 31
November 8, 2006
Chapter 11 - Reactions of Alkyl Halides: Nucleophilic Substitutions and Eliminations
Summary of Substitution and Elimination Reactions
Sometimes it is difficult to tell what mechanism will be the predominant pathway in a reaction.
Usually the most important factor is the substrate. For competing elimination reactions, the base
strength (vs. nucleophile) is key.
R-X
SN1
X
1°
SN2
E1
E2
favored with
good
nucleophile
X
favored with
strong base
can occur with
good
nucleophile
can occur
best if allylic
favored with
strong base
favored if
basic
competes
with SN1
favored with
strong base
doesn't matter
antiperiplanar
required
2°
can occur
best if allylic
3°
favored
competes with E1
X
racemic
100% inversion
Stereochem
Nucleophiles vs Bases
The competition between different reaction mechanisms depends first on the substrate as
summarized above. However, the type of reagent (nucleophile or base) is critical in most cases. It
is improtant to recognize the difference. Alkoxides (tightly held electrons) are good bases, but
terrible nucleophiles.
Good Nucleophiles
I
Br
N3
Cl
CN
Strong Bases
SH
SR
OH
OR
NH2
bulkier is less nucleophilic
C CR
Reaction Examples
Below are several examples of competition between the various reaction pathways.
©2006 Gregory R. Cook
North Dakota State University
page 1
Chem 341
NaCN
Br
CN
1° subtrate
Good nucleophile
Aprotic polar solvent
SN2
HMPA
t-BuOK
Br
1° subtrate
Good Base
Protic polar solvent
E2
tBuOH
O
Br
CH3CO2Na
Br
O
2° subtrate
Good nucleophile
very weak base
SN2
O
NaOEt
E2
SN2
80%
Br
CH3CH2OH
20%
OH
SN1
80%
Br
2° subtrate
Good Base
some subst competes
E1
20%
3° subtrate
Neutral Conditions
Protic polar solvent
NaOEt
3° subtrate
Strong Base
elim wins
E2
EtOH
97%
OH
Cl
HCl
SN1
racemic
O Tos
OH
CN
Tos-Cl
NaCN
Et3N
DMSO
SN2
inversion
OH
Cl (or Br)
PBr3 or SOCl2
NaCN
Et3N
DMSO
SN2 inversion
©2006 Gregory R. Cook
North Dakota State University
CN
page 2
SN2 inversion
NOTE
overall
retention of
configuration
(2 inversions)
Chem 341