substitution and elimination competing reactions
TRANSCRIPT
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Substitution and Elimination
Competing Reactions
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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
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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
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Comparison
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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
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CH3CHCH3
Br
NaOCH2CH3
ethanol, 55°C
CH3CHCH3
OCH2CH3
CH3CH=CH2+
(87%)(13%)
Example
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Br
E2
Figure
CH3CH2 O••
••••–
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Br
SN2
Figure
CH3CH2 O••
••••–
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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?
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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
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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
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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
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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?
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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-
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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
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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
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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
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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
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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
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(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
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Question
Reactions proceeding through this mechanism give a racemic mixture:
A) SN1
B) SN2
C) E1
D) E2
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Question
Methyl bromide reacts with sodium ethoxide in ethanol by this mechanism:
A) SN1
B) SN2
C) E1
D) E2
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Question
3-bromo-3-methylpentane reacts with sodium ethoxide in ethanol by this mechanism:
A) SN1
B) SN2
C) E1
D) E2