Substitution and Elimination

Competing Reactions

Alkyl halides can react with Lewis bases by nucleophilic substitution and/or elimination.

C C

H

X

+ Y:–

C C

Y

H

X:–

+

C C + H Y X:–

+

-elimination

nucleophilic substitution

Two Competing Reactions

How can a prediction be made which reaction pathwayIs followed for a particular alkyl halide?

C C

H

X

+ Y:–

C C

Y

H

X:–

+

C C + H Y X:–

+

-elimination

nucleophilic substitution

Two Competing Reactions

Comparison

A systematic approach is to choose as a referencepoint the reaction followed by a typical alkyl halide(secondary) with a typical Lewis base (an alkoxideion).

The major reaction of a secondary alkyl halidewith an alkoxide ion (a strong base similar to hydroxide) is elimination by the E2 mechanism.

Elimination versus Substitution

CH3CHCH3

Br

NaOCH2CH3

ethanol, 55°C

CH3CHCH3

OCH2CH3

CH3CH=CH2+

(87%)(13%)

Example

Br

E2

Figure

CH3CH2 O••

••••–

Br

SN2

Figure

CH3CH2 O••

••••–

Given that the major reaction of a secondaryalkyl halide with an alkoxide ion is elimination by the E2 mechanism, we can expect the proportion of substitution to increase with:

1) decreased crowding at the carbon that bears the leaving group

When is Substitution Favored?

Question

Which one of the following alkyl halides would be expected to give the highest ratio of

substitution to elimination on treatment with sodium ethoxide in ethanol (50°C)?

A) 1-bromopentane

B) 2-bromopentane

C) 3-bromopentane

D) 2-bromo-3-methylbutane

Decreased crowding at carbon that bears the leaving group increases substitution relative to elimination.

primary alkyl halide

CH3CH2CH2Br

NaOCH2CH3

ethanol, 55°C

CH3CH=CH2+CH3CH2CH2OCH2CH3

(9%)(91%)

Uncrowded Alkyl Halides

primary alkyl halide + bulky base

CH3(CH2)15CH2CH2Br

KOC(CH3)3

tert-butyl alcohol, 40°C

+CH3(CH2)15CH2CH2OC(CH3)3 CH3(CH2)15CH=CH2

(87%)(13%)

But a Crowded Alkoxide Base Can Favor Elimination Even with a Primary Alkyl Halide

Given that the major reaction of a secondaryalkyl halide with an alkoxide ion is elimination by the E2 mechanism, we can expect the proportion of substitution to increase with:

1) decreased crowding at the carbon that bears the leaving group

2) decreased basicity of the nucleophile

When is Substitution Favored?

Question

Which one of the following statements is true?

A) CH3CH2-S- is both a stronger base and

more nucleophilic than CH3CH2-O-

B) CH3CH2-S- is a stronger base but less

nucleophilic than CH3CH2-O-

C) CH3CH2-S- is a weaker base but is more

nucleophilic than CH3CH2-O-

D) CH3CH2-S- is both a weaker base and

less nucleophilic than CH3CH2-O-

Weakly basic nucleophile increases substitution relative to elimination

(70%)CH3CH(CH2)5CH3

CN

KCN

CH3CH(CH2)5CH3

ClpKa (HCN) = 9.1

DMSO

secondary alkyl halide + weakly basic nucleophile

Weakly Basic Nucleophile

Weakly basic nucleophile increases substitution relative to elimination

secondary alkyl halide + weakly basic nucleophile

Weakly Basic Nucleophile

NaN3 pKa (HN3) = 4.6

I

(75%)N3

Question

Which one of the following compounds gives the highest subtitution-to-elimination ratio

(most substitution least elimination) on reaction with 2-bromobutane?

A) NaOCH3

B) NaNH2

C) NaCºND) NaCºCH

Tertiary alkyl halides are so sterically hinderedthat elimination is the major reaction with allanionic nucleophiles. Only in solvolysis reactionsdoes substitution predominate over eliminationwith tertiary alkyl halides.

Tertiary Alkyl Halides

Question

Which one of the following statements is true concerning substitution and elimination intert-butyl bromide?A) the mechanism generally believed to be available to (CH3)3CBr are SN1 and E1B) the mechanism generally believed to be available to (CH3)3CBr are SN1, SN2 and E1C) the mechanism generally believed to be available to (CH3)3CBr are SN1, SN2 and E2D) the mechanism generally believed to be available to (CH3)3CBr are SN1, E1 and E2

(CH3)2CCH2CH3

Br

+CH3CCH2CH3

OCH2CH3

CH3

CH2=CCH2CH3

CH3

CH3C=CHCH3

CH3

+

ethanol, 25°C64% 36%

2M sodium ethoxide in ethanol, 25°C

1% 99%

Example

Question

Reactions proceeding through this mechanism give a racemic mixture:

A) SN1

B) SN2

C) E1

D) E2

Question

Methyl bromide reacts with sodium ethoxide in ethanol by this mechanism:

A) SN1

B) SN2

C) E1

D) E2

Question

3-bromo-3-methylpentane reacts with sodium ethoxide in ethanol by this mechanism:

A) SN1

B) SN2

C) E1

D) E2