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Q. Predict The Stereochemistry of These Products. Are They Single Diastereomers, Enantiomerically Pure, or Racemic, or Something Else ?
Q. Predict The Stereochemistry of These Products. Are They Single Diastereomers, Enantiomerically Pure, or Racemic, or Something Else ?
(a)
N
H
Ph
OTs
(b)
OTs
Ph
KOH
H2S
OH
O
(a)
N
N
H
Ph
OTs
Ph
OTs
KOH
(b)
H2S
HS
SH
SN2
OTs
S
OTs
SN2'
EtO
Tends to occur when R is bulky enough to reduce markedly the rate of direct SN2 displacement.
Example:
Cl
D
OCH3
H
NaOMe
OCH3
Cl
D
NaOMe
H3CO
Cl
O
H
O
But
R=Cl2C6H3-
But
H
N
N
+
/
Examples of SNi reaction
Cl
H3CCH
CHCH2OH
SOCl2
H3C
Ether
CH
CH2
(only)
H3 C
H
C
CH
CH2
SOCl2
H3C
Ether
CH
C
H
CH2Cl
(only)
OH
Mechanism
H3C
H3CCH
CHCH2
Cl
..
.Cl.
CH2
O
S
O
H3 C
CH
CH
Cl
CH2
SO2
Payne rearrangement
S
Ph
Ph
Ph
OH
Ph
OH
Ph
O
OH
Ph
S
OH
S
OH
OH
H2O
NaOH
O
Ph
OH
HNO2
CO2H
OH H2N
H
O
HO
S
OH
N2
O
CO2H
O
O
H
O
Q.
When I undergoes SN1 solvolysis, it reacts more rapidly than isobutyl chloride II.
Explain.
CH3
H3 C
C
H
I
CH2Cl
H3C
C
H
C Cl
H2
II
phenonium ion
H
H3 C
H
H
Cl
H
H3C
H
Cl
TS
+ Cl
H
H3C
H
Sol
OH
Solvolysis products
Cl
H
I
Cl
II
H
OAc
OTs
II
OTs
OAc
HOAc
I
III
Participation of the electrons of the double bond gives the ion III
, which would be stabilized by delocalization of the positive charge
Ph
H2O
Cl
Ph
N
H
CH3CN, heat
Ph
Ph
O
O
O
O
Cl
Ph
Ph
O
N
Ph
O
Ph
Ph
Ph
N
O
OH
O
O
Ph
Ph
N
H
O
R X
NaCN
solvent ?
R CN
NaCN
CH2Cl2, H2O
XR
CN
R X
NaCN
CH2Cl2, H2O
R CN
fast
aq. phase
Na+ CN -
aq. phase
+
Na CN
org. phase
+
Q X
Na+ X-
Q + CN
Q + CN
+
add Q + X -
RX
Q+X
+
CH2Cl2
+
QX = R4N X
RCN
RX
org. phase
CH2Cl2
RCN + X -
Phase- transfer catalysis of the SN2 reaction between NaCN and an alkyl halide
Example
CH3(CH2)7Cl
(in dioxane)
Bu4 NBr
CH3(CH2)7CN
aq. NaCN, 105 0C
(95 %)
CH2 (benzene)
R4 N X
0
aq. KMnO4, 35 C
CH3 (CH2)5COOH
99 %
Crown ethers
O
O
O
K+
O
:O
:O
O:
..
18 - Crown - 6
K + CN
C6H5 CH2Cl
RCH2X
KF
18-C-6
benzene
CH3CN
18-C-6
K+ X -
C6H5 CH2F +
K+ Cl -
RCH2CN
100 %
O
O
O
Na+
O
[15]-crown-5
cavity diameter = 1.7-2.2 A
O
O
inclusion compound
O
O
O
Li+
[12]-crown-4
Crown ethers are named [X]-crown-Y, where X is the total number atoms in the ring
and Y is the number of oxygen atoms in the ring
Host-guest relationship
The hole has diameter 2.7 A
Diameter of K+ = 2.66 A
An ionophorous antibiotic
O
O
O
O
O
Nonactin
an antibiotic
Mustard gas a war gas that produces blisters all over the body surface
..
.S.
Cl
mustard gas
Cl
Cl
Cl
Nu
Cl
Nu
..Nu
CH3 I
CH3Nu +
For nucleophile in a cell, MeI cannot be used, because alkyl halides are insoluble
in water
In biological systems, you have got predominantly aqueous environment
Lets take the case of methylation in the cells of plants and animals:
Here it involves the transfer of a methyl group from an amino acid (methionine)
CH3
H3C
N+ CH2CH2OH
HO
CH3 choline
HO
CH CH2NH CH3
adrenaline
OH
N
CH3
N
nicotine
triphosphate group
OH
nucleophile
O 2C
..
CHCH2CH2SCH3
CH2
NH3
O
O
OH
O
OH
O
OH
leaving
group
Adenine
ATP
CH3
O2CCHCH2CH2
OH
CH2
Adenine
H3N
OH
OH
P
O
OH
NH2
Adenine =
N
OH
O
Triphosphate ion
OH
OH
P
O
OH
CH3
..
N
CH3
HO
CH3
O2CCHCH2CH2
CH2
H
H3N
Adenine
O
H
H
OH
S-Adenosylmethionine (SAM)
CH3
H3C
N
CH3
OH
OH
O2CCHCH2CH2
CH2
H
H3N
Adenine
O
H
choline
H
.
.
.
H
OH
OH
OTs
OTs
Q.
CH3
CH3
O
I
II
OAc
HOAc
OAc
AcOH
..
s
OAc
(+)
OAc
OAc
OAc
(+)
AcOH
Q.
O
Relative rate
1.0
0.014
0.14
4.85 x 10 4
Explain
Transannular participation of ether oxygen
O
..
II
III
Cl
(CD3)2CCD2CH3
(CH3)2CCD2CH3
kD
kH
0.43
H
C
0.71
stabilization by hyperconjugation
Stretching of the -C-H bonds in the activated complex
Since -C-D bonds are somewhat tighter bonds than -C-H bonds, substitution for
-hydrogens lower the extent of stabilization by hyperconjugation in the activated
complex, boost the energy of activation and thus retard the reaction.
H
empty p orbital
H 3C
CH3
H
H
H 2C
CH2
CH2
H
H3C
H2C
CH3
CH2
CH2
CH3
H
H
no stabilization: no electrons
to donate into empty p orbital
The C-H bonds are at 90 to
the empty p orbital and
cannot interact with it
A C-C bond is just as good as the C-H bond in donating electrons into an empty
p orbital and a C-Si bond is even better.
Q.
D
Ph
CH2Cl
D
HCOOH
Product
Me
Me
Cl
HCOOH
Product
..N
..N
II
Cl
H2O
H 2O
Steric acceleration
OH
OH
HCl
HCl
(1
)
(2)