272
NUCLEOPHILIC REACTIONS OF CARBONYL GROUPS
Now we see an analogy with the LAH reduction
sequence (see Section 7.11), in that this ketone
intermediate also reacts with the organometallic
reagent, rather more readily than the initial carboxylic
acid derivative, so that this ketone cannot usually be
isolated. The final product is thus a tertiary alcohol,
which contains two alkyl or aryl groups from the
organometallic reagent.
Note that derivatives of formic acid, HCO 2 H, will
be converted into secondary alcohols by this double
reaction with a Grignard reagent.
secondary
alcohol
R′MgX
OH
R′
H
R′
HCO 2 Et
7.13 Nucleophilic substitution on
derivatives of sulfuric and
phosphoric acids
Phosphorus and sulfur are immediately below nitrogen and oxygen in the periodic table; therefore, we
might expect them to have properties akin to nitrogen
and oxygen. This is true in principle, so that PH 3 and
H 2 S are going to be analogues of NH 3 and H 2 O. We
have already met a number of sulfur derivatives, and
have seen how thiols can be considered to behave in
much the same way as alcohols (see Sections 6.3.2
and 7.4). However, a major difference that is encountered with phosphorus and sulfur arises from the
fact that both have the ability to accommodate more
than eight electrons in the outer electron shell. They
are able to make use of d orbitals in bonding, and
this leads to a greater versatility in bonding and a
range of valencies is available to them. In the common acids phosphoric acid H 3 PO 4 and sulfuric acid
H 2 SO 4 , phosphorus is pentavalent and sulfur is hexavalent. Interestingly, we now find that these atoms
have more in common with carbon than with nitrogen and oxygen. The chemical reactivity of organic
derivatives of phosphoric and sulfuric acids in most
aspects parallels that of carboxylic acid derivatives,
so this is a particularly convenient place to describe
some of the reactions, and to emphasize the similarities.
Most reactions of sulfuric and phosphoric acid
derivatives can be rationalized by considering that the
S=O and P=O functionalities are equivalent to the
carbonyl group, and that polarization in these groups
allows similar nucleophilic reactions to occur. Initial
nucleophilic addition will then be followed by loss
of an appropriate leaving group and regeneration of
the S=O or P=O.
O
C
L
O
S
L
O
P
L
Nu
Nu
Nu
O
7.13.1 Sulfuric acid derivatives
Sulfuric acid can form ester derivatives with alcohols, though since it is a dibasic acid (pK a − 3, 2)
it can form both mono- and di-esters. Thus, acidcatalysed reaction of methanol with sulfuric acid
gives initially methyl hydrogen sulfate, and with a
second mole of alcohol the diester dimethyl sulfate.
Though not shown here, the mechanism will be analogous to the acid-catalysed formation of carboxylic
acid esters (see Section 7.9).
methyl hydrogen sulfate
dimethyl sulfate
sulfuric acid
acid-catalysed
nucleophilic attack
on to S=O
S
HO
OH
O
O
S
HO
OMe
O
O
S
MeO
OMe
O
O
H
MeOH
The simple diesters dimethyl sulfate and diethyl
sulfate are convenient and useful reagents for
alkylation reactions. As derivatives of sulfuric acid,
the alkyl sulfate anions are also the conjugate bases
of strong acids, and are consequently good leaving
groups (see Section 6.1.4).
NUCLEOPHILIC REACTIONS OF CARBONYL GROUPS
Now we see an analogy with the LAH reduction
sequence (see Section 7.11), in that this ketone
intermediate also reacts with the organometallic
reagent, rather more readily than the initial carboxylic
acid derivative, so that this ketone cannot usually be
isolated. The final product is thus a tertiary alcohol,
which contains two alkyl or aryl groups from the
organometallic reagent.
Note that derivatives of formic acid, HCO 2 H, will
be converted into secondary alcohols by this double
reaction with a Grignard reagent.
secondary
alcohol
R′MgX
OH
R′
H
R′
HCO 2 Et
7.13 Nucleophilic substitution on
derivatives of sulfuric and
phosphoric acids
Phosphorus and sulfur are immediately below nitrogen and oxygen in the periodic table; therefore, we
might expect them to have properties akin to nitrogen
and oxygen. This is true in principle, so that PH 3 and
H 2 S are going to be analogues of NH 3 and H 2 O. We
have already met a number of sulfur derivatives, and
have seen how thiols can be considered to behave in
much the same way as alcohols (see Sections 6.3.2
and 7.4). However, a major difference that is encountered with phosphorus and sulfur arises from the
fact that both have the ability to accommodate more
than eight electrons in the outer electron shell. They
are able to make use of d orbitals in bonding, and
this leads to a greater versatility in bonding and a
range of valencies is available to them. In the common acids phosphoric acid H 3 PO 4 and sulfuric acid
H 2 SO 4 , phosphorus is pentavalent and sulfur is hexavalent. Interestingly, we now find that these atoms
have more in common with carbon than with nitrogen and oxygen. The chemical reactivity of organic
derivatives of phosphoric and sulfuric acids in most
aspects parallels that of carboxylic acid derivatives,
so this is a particularly convenient place to describe
some of the reactions, and to emphasize the similarities.
Most reactions of sulfuric and phosphoric acid
derivatives can be rationalized by considering that the
S=O and P=O functionalities are equivalent to the
carbonyl group, and that polarization in these groups
allows similar nucleophilic reactions to occur. Initial
nucleophilic addition will then be followed by loss
of an appropriate leaving group and regeneration of
the S=O or P=O.
O
C
L
O
S
L
O
P
L
Nu
Nu
Nu
O
7.13.1 Sulfuric acid derivatives
Sulfuric acid can form ester derivatives with alcohols, though since it is a dibasic acid (pK a − 3, 2)
it can form both mono- and di-esters. Thus, acidcatalysed reaction of methanol with sulfuric acid
gives initially methyl hydrogen sulfate, and with a
second mole of alcohol the diester dimethyl sulfate.
Though not shown here, the mechanism will be analogous to the acid-catalysed formation of carboxylic
acid esters (see Section 7.9).
methyl hydrogen sulfate
dimethyl sulfate
sulfuric acid
acid-catalysed
nucleophilic attack
on to S=O
S
HO
OH
O
O
S
HO
OMe
O
O
S
MeO
OMe
O
O
H
MeOH
The simple diesters dimethyl sulfate and diethyl
sulfate are convenient and useful reagents for
alkylation reactions. As derivatives of sulfuric acid,
the alkyl sulfate anions are also the conjugate bases
of strong acids, and are consequently good leaving
groups (see Section 6.1.4).