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Elimination Reactions
Two types: E2 E1
E2
Elimination 2-(bi)molecular
Rate [RX][Base]
Base
CH3CH2X
H2C=CH2 +
Base-H +
HO
H H C H
H C H Br
H C C H
H H
H2O
+ Br
E2 reactions (like S N2) take plac e in a single step, without intermediates. The rate of an E2 reaction depends on the concentrat ion of both the alkyl halide and the base, therefore is a bimolecular reaction.
5
MeO MeOH
+ 20 %
The more substituted alkene is the major product because it comes from a more st able transition state, (next sl ide).
6
p 392
Example:
Br
HO H2O
minor product
Br
p 393
10
11
12
p. 395
p 394
13
Conjugated alkene products are preferred over the more substituted alkene product
p 394
Do not use Zaitsevs rule to predict the major product in these cases 14
15 p 396
p. 16 407
p 396
R R C: - < R
tertiary carbanion
R R C: - < H
secondary carbanion
R H C: H
primary carbanion
<
H H C: H
methyl anion
least stable
most stable
18
Eliminations only
HO Cl HO F
HO Cl HO F
HO Br
19
or Br
Br
Br or Br
or Br Br
20
E1
Elimination 1-(mono)molecular
Rate [RX] only
CH3 + H3C C X CH3 H3C C CH2 + Base-H + H3C
Base
X
21
H2O Br
H3O
Br
E1 reactions (like S N1) take plac e in two steps, and involve a carbocation intermediate . The rate of an E1 reaction depends on ly on the concentratio n of the alkyl halide, therefore it is a unimolec ular reaction.
22
p 398
p 400
24
CH3OH Cl
major minor
25
Carbocation rearrangements : Because E1 reactions involve the formation of carbocation intermediates, rearrangements can occur (1,2-hydride or 1,2-methyl shifts ).
26
Examples:
p 400
27
Examples:
p 400
28
Competit ion between E2 and E1 reactions (9.4) An E2 reaction is favored by a high concentrat ion of a strong base and a polar aprotic solvent (e.g. DMSO, DMF ). An E1 reaction is favored by a weak base and a polar protic solvent (H2O, alcohol).
29
Eliminations only...
CH3OH Br H2O Br
CH3O
HO
CH3CH2OH
CH3CH2O Br
E1
E2
30
H+
Cl
CH3OH
31
H+
Cl
CH3OH
H+ H B-
32
Cl
CH3OH
CH3OH H Cl
33
34
When there is a choice of -hydrogens to abstract, the alkene with the bulkiest groups on opposite sides of the C=C (more stable) is the major product. The isomer formed can depend on the configuration of the reactant.
HX
35
Stereochemistry of E2 Elimination
NaOEt Br DMF Heat + +
major
H H3C H H X CH3 H3C H CH3 H FAVORED
PRODUCT
minor
or
B H H H CH3 X CH3 CH3 H CH3 H
Both are POSSIBLE anti-periplanar E2 eliminations from the same alkyl halide. 36 When there is a choice the favored pathway gives a more stable alkene
In the example below there is no choice: H H3C H CH2CH3 X CH3 H3C H CH3 CH2CH3 FAVORED
PRODUCT
37
To reiteratethe particular alkene isomer that is formed depends on the configuration of the reactant
p 406
38
OH
H3C Ph
CH3
H Ph H3C
CH3 H Br
OH
Ph H3C
CH3
Ph
Ph H3C H
Br H CH3
OH
H3 C CH3
Ph H H3C
Br H CH3
OH
H 3C Ph CH 3
39
More problems: : what is the major product? Indicate the stereochemistry where appropriate
HO Br
HO
Cl
HO Cl
40
?
Alkene
H CH3
H3C Br H H C6H5
C6H5
C6H5 C6H5 Br H
H CH3
E2
CH3 C6H5 H H Br C6H5 H3C CH3O in CH3OH (E2 Condns.) H C6H5 C6H5
Me Ph
H Me Ph
Br Ph Me
H Me Ph
Br
H H Br Ph
H Me Ph
Me
Ph EtOH heat
Me Ph
Ph
+
Me Ph
Me
+
Br
Me
Ph
Me Ph
H Ph
42
p 407
43
Examples:
Cl
CH3OH
MAJOR ELIMINATION PRODUCT
CH3OH Br
44
p 409
45
(b)
Cl
CH3CH2O-
p 409
46
Examples
Br
Br Br
CH3
H H
47
p 410
48
p 411
1,2-hydride shift
49
Problem:
Cl CH3 Cl H H CH3
CH3O
Cl Cl
MAJOR E2 PRODUCT
CH3OH
MAJOR E1 PRODUCT
CH3 Cl CH3
50
VERY UNFAVORABLE
H3C CH CH3 3
Br
Br
H3C CH CH3 3
Br H H
H3C Br
CH3 CH3
51
2) decide how much of the product will be the substitution product and how much of the product will be the elimination product
52
3o
1o RX favor SN2
Br CH3O
54
A weak base encourages substitution over elimination A strong base encourages elimination over substitution High temperature encourages elimination SN2/E2 conditions
weak base
CH3COO OCCH3 O CH3COOH Br
strong base
CH3CH2O CH3CH2OH
2o RX
CH3OH high T Br
Br
CH3CH2O-
3o RX
Therefore, if you want to synthesize an alkene the most hindered alkyl halide should be used
Br Br
p. 419
57
OH
O H2
Na+
O
dipropyl ether 1-propoxypropane
The less hindered alkyl group comes from the alkyl halide and the more h indered alkyl group comes from the alkoxide ion.
58
In synthesizing an ether, the less hindered group should be provided by the alkyl halide
1. NaH
OH
O
2. Br
because....
Br
Br + O or 1. NaH O + Br
59
Problems
1. NaH OH 2. I
1. NaH
HO
2.
OH
Br
1. NaH 2. Br
60
OH
CH3 C CH
NH2
Use only primary halides and methyl halides (to favor substitution)
61
Br
Br2, CH2Cl2
Br
2 mol NH2
Br Br
NaNH2 (2 equiv)
62
Br
?
O
?
Br O
63
Br
?
O
Br vicinal Br Br geminal Br
1. a ketone comes from addition of H2O to an a lkyne 2. an alkyne comes from two successive E2 reactions of a vicinal (or geminal) dihalide 3. a vicinal dihalide comes from an alkene 4. the alkene comes from an elimination reaction
Retrosynthetic analysis:
Br
O
Br
Br
Synthesis:
Br O Br2 Br OH
64
Br
NH2
H2O, H+ Hg2+
O
Br
1 2
1. 2.
O intramolecular reaction using OH as nucleophile an alcohol comes from addition of water to an alkene
Retrosynthetic analysis
Br
Br
HO
Br
65
Using any necessary organic and/or inorganic reagents show how the following syntheses can be carried out:
CH3
(1)
(2)
NH2 O HO
(4)
CH3 OH
Br
(5)
CN
Br O
(3)
Cl
Cl Cl
(6)
66
(1) NH2
NH2
Br
HBr Br
NH3 NH2
67
O (2) HO
O HO
Br
HO
HO
HBr
HO
Br
Na
Br O
68
(3)
CN
CN
Br
HBr
Br
CN
CN
69
(4)
CH3 Br
CH3 OH
CH3 OH CH3 Br
CH3
CH3 Br
KO Bu
CH3
CH3 OH
70
Br (5) O
Br
KOtBu
71
Cl (6)
Cl Cl
Cl Cl Cl KO Bu
t
Cl
Cl2
Cl Cl
72