WORKED PROBLEMS
629
(b) Give mechanisms for conversion of estrone into the oestrogen drugs estradiol and ethinylestradiol.
HO
O
HO
OH
HC C
estrone
liq NH 3
ethinylestradiol
HO
OH
estradiol
ether
LiAlH 4
Na
Answer 16.08
Do not be put off by the structures; instead, you should be looking at the functional groups and the changes
involved. The reactions are relatively simple.
(a) You are told cinnamoylcocaine is a diester. The first reaction is merely acid-catalysed hydrolysis of these
two groups. Abbreviate groups as necessary; and provided you make things clear, you will not be required
to give the same mechanism for the second group.
O
O
O
OH
H 2 O
O
OH
R
R
R
OH 2
O
OH
R
OH
H
OH
HO
OH
R
HO
O
OH
R
R
O
OMe
R
O
OH
HOMe
protonation of
carbonyl oxygen
nucleophilic attack of
water onto conjugate acid
− H + , + H +
loss of alcohol
leaving group
− H +
the same reaction occurs on the other ester
H
+
H
+
Ecgonine now reacts with (PhCO) 2 O to give (X). This reagent is benzoyl anhydride, an analogue of acetic
anhydride. The alcohol group reacts, displacing benzoate as leaving group and forming (X), the benzoyl ester
of ecgonine.
Ph
O
Ph
O
O
N
Me
OH
CO 2 H
R OH
Ph
O
Ph
O
O
R
O
Ph
O
N
Me
O
CO 2 H
Ph
O
benzoic anhydride
nucleophilic attack of alcohol
onto anhydride carbonyl
loss of carboxylate
leaving group
− H +
benzoyl ester of ecgonine
(X)
H
The next step is an unusual approach to making an ester via an S N 2 reaction. We usually make esters by
the reaction of alcohols with activated carboxylic acid derivatives like acyl chlorides, or anhydrides as we
have just seen. We do not particularly want to have to convert the carboxylic acid (X) into a more reactive
629
(b) Give mechanisms for conversion of estrone into the oestrogen drugs estradiol and ethinylestradiol.
HO
O
HO
OH
HC C
estrone
liq NH 3
ethinylestradiol
HO
OH
estradiol
ether
LiAlH 4
Na
Answer 16.08
Do not be put off by the structures; instead, you should be looking at the functional groups and the changes
involved. The reactions are relatively simple.
(a) You are told cinnamoylcocaine is a diester. The first reaction is merely acid-catalysed hydrolysis of these
two groups. Abbreviate groups as necessary; and provided you make things clear, you will not be required
to give the same mechanism for the second group.
O
O
O
OH
H 2 O
O
OH
R
R
R
OH 2
O
OH
R
OH
H
OH
HO
OH
R
HO
O
OH
R
R
O
OMe
R
O
OH
HOMe
protonation of
carbonyl oxygen
nucleophilic attack of
water onto conjugate acid
− H + , + H +
loss of alcohol
leaving group
− H +
the same reaction occurs on the other ester
H
+
H
+
Ecgonine now reacts with (PhCO) 2 O to give (X). This reagent is benzoyl anhydride, an analogue of acetic
anhydride. The alcohol group reacts, displacing benzoate as leaving group and forming (X), the benzoyl ester
of ecgonine.
Ph
O
Ph
O
O
N
Me
OH
CO 2 H
R OH
Ph
O
Ph
O
O
R
O
Ph
O
N
Me
O
CO 2 H
Ph
O
benzoic anhydride
nucleophilic attack of alcohol
onto anhydride carbonyl
loss of carboxylate
leaving group
− H +
benzoyl ester of ecgonine
(X)
H
The next step is an unusual approach to making an ester via an S N 2 reaction. We usually make esters by
the reaction of alcohols with activated carboxylic acid derivatives like acyl chlorides, or anhydrides as we
have just seen. We do not particularly want to have to convert the carboxylic acid (X) into a more reactive