S
N
1 vs. S
N
2 vs. E1 vs. E2

Factors affecting the type of reaction an alkyl halide undergoes include:

Type of alkyl halide
 methyl, 1 o , 2 o , 3 o , allylic or benzylic

Strength of nucleophile or base

S
N
1 vs. S
N
2 vs. E1 vs. E2

Guidelines for Predicting Products of
Substitution and Elimination Reactions:

The strength of the nucleophile or base determines the order of the reaction.

S
N
2 and E2 reactions require strong nucleophiles (or bases)

S
N
1 and E1 reactions generally use weak nucleophiles (or bases)

S
N
1 vs. S
N
2 vs. E1 vs. E2

Nucleophilicity (nucleophile strength):
 a measure of the rate at which a nucleophile attacks an electrophilic carbon of a standard substrate

A species with a negative charge is a stronger nucleophile than a similar neutral species:
 nucleophilicity of base > conjugate acid

CH
3
O > CH
3
OH

S
N
1 vs. S
N
2 vs. E1 vs. E2

Nucleophilicity decreases from left to right in the periodic table
 look at the element with lone pair of e -
 more electronegative elements hold on to electrons more tightly

OH > F -

S
N
1 vs. S
N
2 vs. E1 vs. E2

Nucleophilicity increases from top to bottom
 size increases
 electrons held more loosely
 polarizability increases

 bond can begin forming when atoms are farther apart
I > Br -

Polarizable : having electrons that can move more freely toward a positive charge

S
N
1 vs. S
N
2 vs. E1 vs. E2

S
N
1 vs. S
N
2 vs. E1 vs. E2
Example: Identify the stronger nucleophile in each pair. Explain why.
NH
3 or NH
2
-
H
2
O or NH
3
HS or Cl -
PH
3 or NH
3

S
N
1 vs. S
N
2 vs. E1 vs. E2

Base Strength:

Weaker acids produce stronger conjugate bases.
CH
3
CH
2
OH weak acid
CH
3
CH
2
O strong base
strong nucleophile

Strong acids produce weak conjugate bases.
HBr Br-
Strong acid
Weak base good nucleophile

S
N
1 vs. S
N
2 vs. E1 vs. E2

The presence of bulky groups on the
CH
CH
3
C O stronger base.
 carbon
CH
3
C O
-
CH
3
CH
3 t-butoxide ion hindered strong base weak nucleophile
CH
3
CH
2
O
CH
-
3 ethoxide ion unhindered weaker base stronger nucleophile

S
N
1 vs. S
N
2 vs. E1 vs. E2
Example: Identify the stronger base in each pair.
OH or H
2
O
CH
3
OH or CH
3
O -
(CH
3
)
3
CO or CH
3
O -
Water and alcohols are amphoteric. They can serve as either an acid or a base. Water and alcohols are weak acids and weak bases.

S
N
1 vs. S
N
2 vs. E1 vs. E2

Guidelines for Predicting Products of
Substitution and Elimination Reactions:

The type of alkyl halide is important in determining the type of reaction:


Methyl halide: S
N
1 o halide:
2 exclusively

S
N
2 with a strong nucleophile (favored)

E2 with strong base (sometimes)

S
N
1 or E1 are sometimes observed at high temperatures if rearrangement produces more stable carbonium ion

S
N
1 vs. S
N
2 vs. E1 vs. E2

Guidelines for Predicting Products of
Substitution and Elimination Reactions:

The type of alkyl halide is important in determining the type of reaction:

3 o Halides:

E2 with a strong base

S
N
1 and E1 with weak nucleophile or weak base

S
N
1 vs. S
N
2 vs. E1 vs. E2

Guidelines for Predicting Products of
Substitution and Elimination Reactions:

The type of alkyl halide is important in determining the type of reaction:

2 o Halides:

Mixtures of products are common

Strong base/nucleophile gives S
N
2 and
E2

Weak base/nucleophile gives S
N
1 and
E1

S
N
1 vs. S
N
2 vs. E1 vs. E2

Guidelines for Predicting Products of
Substitution and Elimination Reactions:

Strong bulky bases favor E2 reactions.
 t-butoxide ion

Good nucleophiles with limited basicity favor S
N
2 reactions.

Br -

I -

CH CH
3
OH
2
OH
S
N
1 vs. S
N
2 vs. E1 vs. E2
CH
3 mechanism of the following reaction. If more
CH
CH
3 2 2
OCH
CH explain which is/are most likely.
CH
CH
3
CH
CH
2
2
CH CH OH
Br + NaOCH
CH
3
OH
3
3
CH
3
CH
2
OCH
3 major
+
CH
3
CH
2
OCH
3
CH
2
CH
2 minor
CH
3
CH
2
OCH
3
NaOCH
3
CH
2
CH
2
3
N
2
2 or E2
3
1 o Halide favors S
N
2 over E2
Br + NaOCH
3
CH
3
CH
2
Br + NaOCH
3

S
N
1 vs. S
N
2 vs. E1 vs. E2
Example: Predict the product(s) and mechanism of the following reaction. If more
2
CH
3
CH
3
CH than one product or mechanism is possible,
3
CH
2
OH explain which is/are most likely.
CH
3
CHCH
3
Br
CH
3
2
CH
2
CH
3 3
CH
3 3
CH OH
2
OH
CH
CH
3
3
CH
3
CH
CHCH
NaOCH
2
3
CH
CH
OCH
CH
3
CH
2
2
CH
3
OH
2
3
2
+ CH
3
CH CH
2
NaOCH
2
CH
3
= strong base/nucleophile
3 3 3 3
3
CHCH
3
CHCH
3 3
2nd order kinetics S 2 or E2
2 2
CH
3 3
3
CH
3
CHCH
3
Br OCH
2
CH
3 Relative amounts of S N 2 vs E2 depends on temperature.

S
N
1 vs. S
N
2 vs. E1 vs. E2
Example:
CH
3
OH
CH
3
OH
Predict the product(s) and
CH
3
D mechanism of the following reaction. If more
OH
CH explain which is/are most likely.
D
OH
CH than one product or mechanism is possible,
Br
Br
3
CH
3
Br

CH
Br

3
3
OH
3
OCH
3
CH
3
OCH
3
+ CH
CH
3
+
CH
3
CH
3
CH
OH = weak nucleophile or weak base
CH
CH
2
Br
3
CH
Br major
2
3
N
CH major
3
OCH
1 or E1
3
CH
3
OCH
CH
CH
2 trace
CH
CH
3
OCH
OCH
3
CH
3
CH
2
CH
3
CH
2