Download Elimination Reactions - result in the formation of a new π

Chemistry 2500 Lecture Notes
Chapter 8 Elimination Reactions
Page 1 of 14
Elimination Reactions - result in the formation of a new p-bond
CH3
H
H C
H
C
OH
H2SO4, D
C
CH3
H3C C
H3C
C
H
Br
H
CH3
H
C
CH3
KOH
CH3CH2OH H3C
CH3
CH3
H
C
H3C
H OSO2CH3
H
H
C
CH3
H
NaOCH2CH3
CH3CH2OH
H
The E1 reaction starts off like SN1:
CH3
H
H C
H
C
H OSO3H
H C
H
OH
CH3
H
H C
H
H
CH3
C OSO3H
CH3
CH3
OSO3H
C
CH3
H
CH3
C
H
C
CH3
E1 reaction is always a possibility where there is a carbocation intermediate.
If E1 is the desired reaction, the use of H2SO4 or H3PO4 and heat is best.
Chemistry 2500 Lecture Notes
Chapter 8 Elimination Reactions
Page 2 of 14
E1 reactions usually give the most subsituted alkene
HO H
H2SO4, ∆
3
7
H
H
H
H
H
H
H
H H
"Saytzeff" products
(via thermodynamic
control)
H
H
H
H
H H
H
Energy
Alkene Stability
-27.6 kcal/mol
H
CH3
C C
H3C
H
-30.3 kcal/mol
-28.6 kcal/mol
H
H
C C
H3C
CH3
H
H
C C
H
CH2CH3
H2, Pd/C
CH3CH2CH2CH3
1.) Alkenes with more substituents tend to be more stable than those with less substituents.
2.) trans-Alkenes tend to be more stable than cis-alkenes (this applies to disubstitued alkenes)
Chemistry 2500 Lecture Notes
Chapter 8 Elimination Reactions
Page 3 of 14
Alkyl halides can also undergo E1
H
CH3
H C
H
C
CH3
H2O
CH3CH2OH
CH3
H
C
Br
H
H C
H
C
H
CH3
64%
CH3
C
CH3
Br
H
H C
H
C
CH3
OH
36%
H
H
H C
H
CH3
CH3
H C
H
CH3
H
CH3
C
OH
CH3
C
CH3
C
C
H
CH3
There are (in principle) as many possible products in elimination reactions as
there are unique types of b-hydrogens (b to the leaving group).
CH3
Cl
CH3CH2OH
DMSO
CH3
H H
H
H
C H
CH2
H H
H
H
C H
Chemistry 2500 Lecture Notes
Chapter 8 Elimination Reactions
Page 4 of 14
The E2 Reaction
H 3C H
C
Br
H3CH2C
H 3C H
C
H3CH2C
CH3CH2O-Na+
Ethanol, 25¡
H3C H
C
4 M KOH,
Ethanol, 80¡
CH3(CH2)15CH2CH2Br
H3C H
C
H3CH2C
1M CH3O-Na+,
CH3OH, 65¡ C
H3CHC CHCH3
18%
H3CH2C
Br
OCH2CH3
66%
OH
CH3(CH2)15CH2CH2Br
16%
H3CHC CHCH3
9%
H3CH2CHC CH2
75%
CH3(CH2)15CH2CH2OCH3
16%
H3C(H2C)15HC CH2
1%
96%
H3C
H 3C
1M
C
H3CH2CHC CH2
O- K+
CH3
H3C
t-Butanol, 80¡C
H3C(H2C)15H2CH2C O C
12%
CH3
CH3
H3C(H2C)15HC CH2
85%
Chemistry 2500 Lecture Notes
Chapter 8 Elimination Reactions
Page 5 of 14
The Stereochemistry of the E2 Reaction
In an E2 reaction, a strong base removes a proton beta to the leaving group so long as there exists a
conformation in which the proton is anti-periplanar to the leaving group. Where there are several such
protons, several products are possible:
HO_
bH
bH
aH
b
CH3
H
C C
C C
Br
H3C
CH3
HO_
HO
H 3C
_
H
H CH CH
2
3
C C
H
Br
H
H
H
H 3C
H
CH3
H
C C
H
C C
H3C
Br
CH3
H
H2C CHCH2CH3
The E2 reaction is an example of a st er eo sp ecif ic reaction:
H Ph
H
H3C
Ph
C C
Br
NaOEt,
EtOH
H3C
C C
Ph
Ph
H
H 3C
Ph
H
CH3
Ph
H
C C
Br
NaOEt,
EtOH
H3C
Ph
C C
H
Ph
H
Ph
H
Ph
H
H
Ph
Ph
CH3
Br
The corresponding E1 reaction is not stereospecific:
Ph
H
Ph
CH3
Br
Ph
Ph
H
CH3
Chemistry 2500 Lecture Notes
Chapter 8 Elimination Reactions
H
t-BuO_K+
H H3C
H3C
DMSO, 55¡C
H
TsO
H
H
H
OTs
H
CH3
OTs
H
H
H
H
H
OTs
CH3
H
H
H
Page 6 of 14
t-BuO_K+
t-BuO_K+
DMSO, 55¡C
DMSO, 55¡C
Ph
H
H
Ph
OTs
B:
H
H
C
H3C
Ph
CH3
NaOEt,
EtOH
C
OTs
H3C
Ph
CH3
C
C
H
Ph
H
Chemistry 2500 Lecture Notes
Chapter 8 Elimination Reactions
Page 7 of 14
Competition between SN2 and E2
Sn2
I
H 3C H
C
-
H CH
3
C
Acetone
Br
I
H3C
Sn2
H 3C H
C
-
CH3CH2O
CH3CH2O
H
H2
C H
C
Ethanol, 55¡
Br
CH3CH2O
H CH
3
C
-
H
Br
H2
C CH3
C Br
H3C
+ Br
-
21%
CH3
Ethanol, 55¡
CH3CH2OH
H2C
C
H3C
CH3CH2O
-
CH3
H3C
-
+ Br
H
+ Br
-
79%
H3C
Ethanol, 55¡
CH3CH2OH
H2C
C
H 3C
CH3
+ Br
-
100%
Chemistry 2500 Lecture Notes
Chapter 8 Elimination Reactions
Page 8 of 14
Alkynes can be prepared by E2 processes:
Cl Cl
C
Vicinal dihalide
C
H H
Geminal dihalide
H
Cl
C
Cl H
C
C
H
Cl
C
C
H
K Ot-Bu
DMSO, 130°
Br
C
H
Br
Br
K Ot-Bu
Ether/THF
83%
Br
Br
H
Br
LDA, THF
LDA, THF
56%
Chemistry 2500 Lecture Notes
Chapter 8 Elimination Reactions
Page 9 of 14
Table 8.2 Elimination vs Substitution
Substrate
Strong nucleophile/Weak base Strong base
Weak nucleophile
(e.g. H2O, ROH, H2SO4) (e.g. halides, NC-, RS-)
(e.g. HO-, RO-, R2N-)
1° Halides/sulphonates
No reaction
SN2
SN2 with unhindered base
(HO-, CH3O-)
E2 with bulky base (LDA,
t-BuO-)
1° Alcohols
(when protonated by
strong acid)
No reaction
SN2
Br¿nsted A/B
2° Halides/Sulphonates
No reaction
No reaction
E2
2° Alcohols
(when protonated by
strong acid)
No reaction
SN2, E2 at high T
Br¿nsted A/B
3° Halides/Sulphonates
SN1 and E1
E1 dominates at high T
No reaction
E2
3° Alcohols
(when protonated by
strong acid)
E1
SN1 and E1
Br¿nsted A/B
Chemistry 2500 Lecture Notes
Chapter 8 Elimination Reactions
Page 10 of 14
Oxidation levels of organic compounds
H
H
H
C
H
H
C
OH
H
H
H
O
O
C
C
H
H
Least oxidized
O
C
O
OH
Most oxidized
It is often useful to recognize that the number of heteroatoms (non C or H)
attached to a carbon reflect its oxidation level. Carbon atoms with the same
number of heteroatoms attached are in equivalent oxidation levels and often can
be interconverted using non-Redox reactions:
H
H
C
H
Cl
H
C
H
OH
H
H
H
C Br
Br
C
H
O
H3C
C
N
H3C
C
C OCH3
OCH3
O
O
OH
H3C
C
N
NH2
C
H3C
O
Chemistry 2500 Lecture Notes
Chapter 8 Elimination Reactions
Page 11 of 14
Some oxidations are elimination reactions
H
LG
C
C
H
LG
C
O
H
H H
H
The Swern Oxidation - a mild, convenient, if smelly way to make aldehydes
and ketones
O
H2
C
1)
H3C
OH
O
S
Cl
C
Cl
C
CH3
H
-78°
O
C
O
2) N(CH2CH3)3
O
Cl
H3C
C
Cl
Cl
O
O
S
C
O
C
O
CH3
H3C
S
C
O
Cl
Cl
C
O
O
CH3
H3C
S
Cl
H3C
S
Cl
O
CH3
C
O
C
O
Cl
C
O
CH3
Cl
Chemistry 2500 Lecture Notes
H H
R C OH
Chapter 8 Elimination Reactions
H H
R C O
H3C
S
Cl
H3C
H
Page 12 of 14
CH3
Cl
S
CH3
H H
R C O
Et3N:
H H
R C O
CH3
Et3NH
CH3
R
C
S
CH3
CH3
H
S
CH3
S
CH3
O
What about this possibility?
B:
R
H
O
R
C
X
O
C
H
H
And this?
B:
X
R
H
O
C
R
H
O
C
H
H
Biological systems us NAD+ or NADP+ as a hydride acceptor.
H
O
O
H2N
H
C
R
C
HO
H
H
N
O
P O
O
O
O
O
O
H
H
O
P
H
OH HO
H
OH
H
H O H N
N
N
N
H2N
Chemistry 2500 Lecture Notes
Chapter 8 Elimination Reactions
1° Alcohol
The oxidation
of alcohols
CH2OH
[O]
[O]
O
Aldehyde
OH
[O]
C
C
H
OH
Carboxylic acid
O
OH
O
[O]
Page 13 of 14
[O]
NR
2° Alcohol
Ketone
3° Alcohol
Reagents
H
N
CrO3 N
2
Collin's Reagent
H2CrO4, H2SO4
KMnO4
Jone's Reagent Your name here!
-
CrO3Cl
Corey's Reagent
Collin's
CH2OH
CHO
CH2Cl2, 20°C
85%
Corey's
OH
C
CH2Cl2, 20°C
OH
Cl3C(CH2)3CH2OH
Jone's
FCH2(CH2)9CO2H 93%
Cl3C(CH2)3CO2H
O
OH
H3C
95%
1) KMnO4, H2O, Na2CO3
2) H3O+
OH
92%
O
Jone's
FCH2(CH2)9CH2OH
O
H
MnO2
Acetone 25°C
H 3C
OH
84%
92%
Chemistry 2500 Lecture Notes
Chapter 8 Elimination Reactions
Page 14 of 14
Chemistry 2500 – Summary of Oxidation Reaction
Type of alcohol
Oxidation reaction
Result
H
Primary
R
OH
O
[O]
R
H
H
Primary
R
OH
R
R'
R
OH
O
O
[O]
R
H
Aldehydes under mild oxidation conditions
O
[O]
H
Secondary
H
R'
Carboxylic acids under aggresive oxidation conditions
H
Ketones under all oxidation conditions,
mild conditions generally prefered
R'
Tertiary
R
OH
[O]
No reaction because no H to eliminate
R''
Name of reagent
Reagent/condition
Result
Swern
1 DMSO, ClCOCOCl
2 NEt3
°1 ROH to aldehyde
°2 ROH to ketone
CH3
Cl
+
S
CH
Enzymes (alcohol dehydrogenase)
3
{active agent is
}
+
+
NAD or NADP “coenzyme”
Collin’s reagent
CrO3.py2 in CH2Cl2 at R.T.
°1 ROH to aldehyde
°2 ROH to ketone
Corey’s reagent
PCC = (pyH+)(CrO3Cl)–
°1 ROH to aldehyde
°2 ROH to ketone
Jones’ reagent
(high valence Cr in acid condit.)
CrO3 in H2SO4 = “H2Cr2O7”
or CrO3 in CH3COOH
°1 ROH to carboxylic acids
(°2 ROH to ketone – not best!)
MnO4–
(high valence Mn in base condit.)
1 MnO4– in H2O, OH–
2 H3O+ (workup to release acid)
°1 ROH to carboxylic acids
(°2 ROH to ketone – not best!)
MnO2 (freshly prepared)
MnO2 in acetone, R.T.
or MnO2 in benzene, R.T.
Allylic and benzylic alcohols only
°1 ROH to aldehyde
°2 ROH to ketone
°1 ROH to aldehyde
°2 ROH to ketone