Chemistry Reference
In-Depth Information
Me
Me
Cl
1% TBAC, 20-45
°
C, 2.5 h
Cl
+
H
2
N
Br
N
Br
NaOH, H
2
O, THF
O
O
86% yield
Scheme 10.31
Ar'
CCOOMe
CCOOMe
N
Ar'
Ar'
Pb, CBr
2
F
2
,
Ar
F
F
+
N
N
-
TBAB
45ºC
CF
2
Ar
Ar
MeOOC
1-4 h
COOMe
Ar'
N
Ar
F
yield 30-70%
MeOOC
COOMe
Scheme 10.32
aqueous phase to react with charged or hydrophilic
species. This methodology, which has great potential
for water-based 'green' organic syntheses, is termed
'inverse PTC' and is based on three different mecha-
nisms of organic/aqueous transport:
late [166] (formate to octanoate) and dicarboxylate
[167] (oxalate to adipate, maleate, fumarate and
phthalate) anions. Additional kinetic studies were
carried out with PNO-catalysed reactions of
chlorobenzoyl chloride [168] or dichlorobenzoyl
chloride [169] with chlorobenzoate, bromobenzoyl
bromide with bromobenzoate [170] and fluoro- and
butylbenzoyl chloride with benzoate [171]. It was
resolved that this family of reactions proceeded via
the following four-step mechanism:
(1)
Reversible conversion of an organophilic sub-
strate into an ionic water-soluble intermediate.
(2)
Complexation of organic substrates by highly
hydrophilic cyclodextrins or water-soluble
calixarenes.
(3)
Solubilisation of organic substrates by aqueous
micellar systems.
(1)
Formation of ionic intermediate between the
catalyst and the acyl halide in the organic phase:
RCOCl
(org)
+ PNO
(org)
Æ RCOONP
+
Cl
-
(org)
.
(2)
Transport of the intermediate salt from the
organic to the aqueous phase: RCOONP
+
Cl
-
(org)
Æ RCOONP
+
Cl
-
(aq)
.
(3)
Aqueous phase reaction of the intermediate
with the carboxylate anion: RCOONP
+
Cl
-
(aq)
+
R¢COO
-
(aq)
Æ RCOOCOR¢
(aq)
+ PNO
(aq)
.
(4)
Extraction of the product and the catalyst into
the organic phase: RCOOCOR¢
(aq)
+ PNO
(aq)
Æ
RCOOCOR¢
(org)
+ PNO
(org)
.
Inverse PTC was introduced originally by Mathias
[161], who studied the catalytic effect of 4-
N
,
N
-
dimethylaminopyridine (DMAP) on the acylation
reaction of alanine with acyl halides in a water/
organic two-phase system. Fife [162] described a
related reaction of acyl halides in the organic phase
with carboxylate anions in aqueous phase to yield
anhydrides catalysed by pyridine
N
-oxide (PNO).
Both groups argue for the formation of a water-
soluble acylpyridinium intermediate, which transfers
the acyl halide into the aqueous phase to encounter
the other substrate. The kinetics and mechanism of
inverse PTC PNO-catalysed anhydride formation was
studied profoundly by Jwo. Some examples are the
reactions of benzoyl chloride with benzoate [163],
acetate [164] and butanoate [165] simple carboxy-
Based on a comprehensive kinetic study it was
concluded that the rate-limiting step in the anhy-
dride formation mechanism is the aqueous phase
ion-pair generation (step 1). The kinetics was found
to follow a pseudo-first-order rate law, with the rate
constant being a linear function of the PNO catalyst
