8.118.11

Substitution and EliminationSubstitution and Elimination

as Competing Reactionsas Competing Reactions

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

CC CC

HH

XX

++ YY::––

CC CC

YY

HH

XX::––

++

CC CC ++ HH YY XX::––

++

ββ-elimination-elimination

nucleophilic nucleophilic substitutionsubstitution

Two Reaction TypesTwo Reaction Types

How can we tell which reaction pathway is How can we tell which reaction pathway is followed for a particular alkyl halide?followed for a particular alkyl halide?

CC CC

HH

XX

++ YY::––

CC CC

YY

HH

XX::––

++

CC CC ++ HH YY XX::––

++

ββ-elimination-elimination

nucleophilic nucleophilic substitutionsubstitution

Two Reaction TypesTwo Reaction Types

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

The major reaction of a secondary alkyl halideThe major reaction of a secondary alkyl halidewith an alkoxide ion is elimination by the E2with an alkoxide ion is elimination by the E2mechanism.mechanism.

Elimination versus SubstitutionElimination versus Substitution

CHCH33CHCHCHCH33

BrBr

NaNaOOCHCH22CHCH33

ethanol, 55ethanol, 55°°CC

CHCH33CHCHCHCH33

OOCHCH22CHCH33

CHCH33CH=CHCH=CH22++

(87%)(87%)(13%)(13%)

ExampleExample

BrBr

E2E2

Figure 8.8Figure 8.8

CHCH33CHCH22 OO••••

••••••••––

BrBr

SSNN22

Figure 8.8Figure 8.8

CHCH33CHCH22 OO••••

••••••••––

Given that the major reaction of a secondaryGiven that the major reaction of a secondaryalkyl halide with an alkoxide ion is eliminationalkyl halide with an alkoxide ion is eliminationby the E2 mechanism, we can expect theby the E2 mechanism, we can expect theproportion of proportion of substitutionsubstitution to increase with: to increase with:

1)1) decreased crowding at the carbon thatdecreased crowding at the carbon thatbears the leaving groupbears the leaving group

When is Substitution Favored?When is Substitution Favored?

QuestionQuestion

Which one of the following alkyl halides wouldWhich one of the following alkyl halides wouldbe expected to give the highest ratio ofbe expected to give the highest ratio of

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

A)A) 1-bromopentane1-bromopentane

B)B) 2-bromopentane2-bromopentane

C)C) 3-bromopentane3-bromopentane

D)D) 2-bromo-3-methylbutane2-bromo-3-methylbutane

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

primary alkyl halideprimary alkyl halide

CHCH33CHCH22CHCH22BrBr

NaNaOOCHCH22CHCH33

ethanol, 55ethanol, 55°°CC

CHCH33CH=CHCH=CH22++CHCH33CHCH22CHCH22OOCHCH22CHCH33

(9%)(9%)(91%)(91%)

Uncrowded Alkyl HalidesUncrowded Alkyl Halides

primary alkyl halide + bulky baseprimary alkyl halide + bulky base

CHCH33(CH(CH22))1515CHCH22CHCH22BrBr

KKOOC(CHC(CH33))33

tert-tert-butyl alcohol, 40butyl alcohol, 40°°CC

++CHCH33(CH(CH22))1515CHCH22CHCH22OOC(CHC(CH33))33 CHCH33(CH(CH22))1515CH=CHCH=CH22

(87%)(87%)(13%)(13%)

But a Crowded Alkoxide Base Can FavorBut a Crowded Alkoxide Base Can FavorElimination Even with a Primary Alkyl HalideElimination Even with a Primary Alkyl Halide

Given that the major reaction of a secondaryGiven that the major reaction of a secondaryalkyl halide with an alkoxide ion is eliminationalkyl halide with an alkoxide ion is eliminationby the E2 mechanism, we can expect theby the E2 mechanism, we can expect theproportion of proportion of substitutionsubstitution to increase with: to increase with:

1)1) decreased crowding at the carbon thatdecreased crowding at the carbon thatbears the leaving groupbears the leaving group

2) decreased basicity of the nucleophile2) decreased basicity of the nucleophile

When is Substitution Favored?When is Substitution Favored?

QuestionQuestion

Which one of the following statements is Which one of the following statements is truetrue??A)A) CHCH33CHCH22-S-S-- is both a stronger base and is both a stronger base and more more nucleophilic nucleophilic than CH3CHthan CH3CH2-2-OO

--

B)B) CHCH33CHCH22-S-S-- is a stronger base but less is a stronger base but less nucleophilic nucleophilic than CHthan CH33CHCH2-2-OO

--

C)C) CHCH33CHCH2-2-SS-- is a weaker base but is more is a weaker base but is more

nucleophilic nucleophilic than CHthan CH33CHCH2-2-OO--

D)D) CHCH33CHCH2-2-SS- - is both a weaker base and is both a weaker base and

less less nucleophilic nucleophilic than CHthan CH33CHCH2-2-OO--

Weakly basic nucleophileWeakly basic nucleophile increases increases substitution substitution relative to eliminationrelative to elimination

(70%)(70%)CHCH33CH(CHCH(CH22))55CHCH33

CNCN

KCNKCN

CHCH33CH(CHCH(CH22))55CHCH33

ClClppKKaa (HCN) = 9.1 (HCN) = 9.1

DMSODMSO

secondary alkyl halide + secondary alkyl halide + weakly basic nucleophileweakly basic nucleophile

Weakly Basic NucleophileWeakly Basic Nucleophile

Weakly basic nucleophileWeakly basic nucleophile increases increases substitution substitution relative to eliminationrelative to elimination

secondary alkyl halide + secondary alkyl halide + weakly basic nucleophileweakly basic nucleophile

Weakly Basic NucleophileWeakly Basic Nucleophile

NaNaNN33 ppKKaa (HN (HN33) = 4.6) = 4.6

II

(75%)(75%)

NN33

QuestionQuestion

Which one of the following compounds gives theWhich one of the following compounds gives thehighest highest subtitutionsubtitution-to-elimination ratio-to-elimination ratio

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

A)A) NaOCHNaOCH33

B)B) NaNHNaNH22

C)C) NaCNaC≡≡NN

D)D) NaCNaC≡≡CHCH

Tertiary alkyl halides are so Tertiary alkyl halides are so sterically sterically hinderedhinderedthat elimination is the major reaction with allthat elimination is the major reaction with allanionic anionic nucleophilesnucleophiles. Only in . Only in solvolysis solvolysis reactionsreactionsdoes substitution predominate over eliminationdoes substitution predominate over eliminationwith tertiary alkyl halides.with tertiary alkyl halides.

Tertiary Alkyl HalidesTertiary Alkyl Halides QuestionQuestion

Which one of the following statements is Which one of the following statements is truetrue concerning concerningsubstitution and elimination insubstitution and elimination interttert-butyl bromide?-butyl bromide?A)A) the mechanism generally believed to be the mechanism generally believed to be availableavailableto (CHto (CH33))33CBr are SCBr are SNN1 and E11 and E1B)B) the mechanism generally believed to be the mechanism generally believed to be availableavailableto (CHto (CH33))33CBr are SCBr are SNN1, S1, SNN2 and E12 and E1C)C) the mechanism generally believed to be the mechanism generally believed to be availableavailableto (CHto (CH33))33CBr are SCBr are SNN1, S1, SNN2 and E22 and E2D)D) the mechanism generally believed to be the mechanism generally believed to be availableavailableto (CHto (CH33))33CBr are SCBr are SNN1, E1 and E21, E1 and E2

(CH(CH33))22CCHCCH22CHCH33

BrBr

++CHCH33CCHCCH22CHCH33

OOCHCH22CHCH33

CHCH33

CHCH22=CCH=CCH22CHCH33

CHCH33

CHCH33C=CHCHC=CHCH33

CHCH33

++

ethanol, 25ethanol, 25°°CC64%64% 36%36%

22MM sodium sodium ethoxide ethoxide in ethanol, 25in ethanol, 25°°CC

1%1% 99%99%

ExampleExampleQuestionQuestion

Reactions proceeding through this mechanismReactions proceeding through this mechanismgive a give a racemic racemic mixture:mixture:

A)A) SSNN11

B)B) SSNN22

C)C) E1E1

D)D) E2E2

Question 9Question 9

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

A)A) SSNN11

B)B) SSNN22

C)C) E1E1

D)D) E2E2

QuestionQuestion

3-bromo-3-methylpentane reacts with sodium3-bromo-3-methylpentane reacts with sodiumethoxide ethoxide in ethanol by this mechanism:in ethanol by this mechanism:

A)A) SSNN11

B)B) SSNN22

C)C) E1E1

D)D) E2E2