NUCLEOPHILIC SUBSTITUTION ON DERIVATIVES OF SULFURIC AND PHOSPHORIC ACIDS
273
Nu
good leaving group through resonance stabilization
S N 2
S N 2 nucleophilic attack
alkylation of
nucleophile
S
O
OMe
O
O
dimethyl sulfate
Me
Nu Me
S
O
OMe
O
O
S
O
OMe
O
O
S
O
OMe
O
O
Table 7.4 Comparisons of carboxylic and sulfonic acid derivatives
Carboxylic acid derivative
Sulfonic acid derivative
RCO.OH
Carboxylic acid
RSO 2 .OH
Sulfonic acid
RCO.Cl
Acyl chloride
RSO 2 .Cl
Sulfonyl chloride
RCO.OR
Carboxylate ester
RSO 2 .OR
Sulfonate ester
RCO.NH 2
Amide
RSO 2 .NH 2
Sulfonamide
Compounds that are even better analogues of carboxylic acids are produced when an alkyl or aryl
group replaces one of the hydroxyls in sulfuric
acid. This provides compounds called sulfonic acids,
which in turn give rise to a range of derivatives
exactly comparable to those we have met as carboxylic acid derivatives (Table 7.4).
As with the carboxylic acid group, the reactivity of these sulfonic acid derivatives may be predicted from the properties of the leaving group,
and sulfonyl chlorides are the most reactive (see
Section 7.8). Other classes of derivatives are thus
most conveniently prepared from the sulfonyl chloride. Reaction with an alcohol leads to formation
of a sulfonate ester. Two common sulfonyl chloride reagents employed to make sulfonate esters
from alcohols are p-toluenesulfonyl chloride, known
as tosyl chloride, and methanesulfonyl chloride,
known as mesyl chloride (see Section 6.1.4). Note
the nomenclature tosyl and mesyl for these groups,
which may be abbreviated to Ts and Ms respectively.
tosyl (Ts)
mesyl (Ms)
tosyl chloride
(p-toluenesulfonyl chloride)
mesyl chloride
(methanesulfonyl chloride)
S
Me
Cl
O
O
S
Me
O
O
S
Cl
O
O
H 3 C
S
O
O
H 3 C
MsCl
TsCl
The reaction of tosyl chloride with an alcohol
is easily represented by the standard nucleophilic
substitution sequence, and gives a sulfonate ester
called a tosyl ester.
R OTs
tosyl ester
tosyl chloride
(p-toluenesulfonyl chloride)
S
Cl
O
O
H 3 C
S
OR
O
O
H 3 C
TsCl
ROH
Tosyl esters are good alkylating agents, rather like
dimethyl sulphate above, and for the same reason, i.e.
the presence of a good resonance-stabilized leaving
group, the tosylate anion. This is the conjugate base
of p-toluenesulfonic acid, a strong acid (pK a − 1.3).
Thus, tosyl chloride may be used to facilitate
nucleophilic substitutions.
Hydroxide is a poor leaving group, and nucleophilic reactions on alcohols are not particularly
favourable unless acidic conditions are used to
273
Nu
good leaving group through resonance stabilization
S N 2
S N 2 nucleophilic attack
alkylation of
nucleophile
S
O
OMe
O
O
dimethyl sulfate
Me
Nu Me
S
O
OMe
O
O
S
O
OMe
O
O
S
O
OMe
O
O
Table 7.4 Comparisons of carboxylic and sulfonic acid derivatives
Carboxylic acid derivative
Sulfonic acid derivative
RCO.OH
Carboxylic acid
RSO 2 .OH
Sulfonic acid
RCO.Cl
Acyl chloride
RSO 2 .Cl
Sulfonyl chloride
RCO.OR
Carboxylate ester
RSO 2 .OR
Sulfonate ester
RCO.NH 2
Amide
RSO 2 .NH 2
Sulfonamide
Compounds that are even better analogues of carboxylic acids are produced when an alkyl or aryl
group replaces one of the hydroxyls in sulfuric
acid. This provides compounds called sulfonic acids,
which in turn give rise to a range of derivatives
exactly comparable to those we have met as carboxylic acid derivatives (Table 7.4).
As with the carboxylic acid group, the reactivity of these sulfonic acid derivatives may be predicted from the properties of the leaving group,
and sulfonyl chlorides are the most reactive (see
Section 7.8). Other classes of derivatives are thus
most conveniently prepared from the sulfonyl chloride. Reaction with an alcohol leads to formation
of a sulfonate ester. Two common sulfonyl chloride reagents employed to make sulfonate esters
from alcohols are p-toluenesulfonyl chloride, known
as tosyl chloride, and methanesulfonyl chloride,
known as mesyl chloride (see Section 6.1.4). Note
the nomenclature tosyl and mesyl for these groups,
which may be abbreviated to Ts and Ms respectively.
tosyl (Ts)
mesyl (Ms)
tosyl chloride
(p-toluenesulfonyl chloride)
mesyl chloride
(methanesulfonyl chloride)
S
Me
Cl
O
O
S
Me
O
O
S
Cl
O
O
H 3 C
S
O
O
H 3 C
MsCl
TsCl
The reaction of tosyl chloride with an alcohol
is easily represented by the standard nucleophilic
substitution sequence, and gives a sulfonate ester
called a tosyl ester.
R OTs
tosyl ester
tosyl chloride
(p-toluenesulfonyl chloride)
S
Cl
O
O
H 3 C
S
OR
O
O
H 3 C
TsCl
ROH
Tosyl esters are good alkylating agents, rather like
dimethyl sulphate above, and for the same reason, i.e.
the presence of a good resonance-stabilized leaving
group, the tosylate anion. This is the conjugate base
of p-toluenesulfonic acid, a strong acid (pK a − 1.3).
Thus, tosyl chloride may be used to facilitate
nucleophilic substitutions.
Hydroxide is a poor leaving group, and nucleophilic reactions on alcohols are not particularly
favourable unless acidic conditions are used to