268 J. CHEM. RESEARCH (S), 1998
J. Chem. Research (S),
1998, 268±269$
1,3,4-Oxadiazolethiol as Acyl-transfer Reagent in
Acylation of Amines: a One-pot Reaction$
B. N. Goswami,* N. Borthakur and A. C. Ghosh
Organic Chemistry Division, Regional Research Laboratory, Jorhat-785006, India
Amines are acylated using 5-(2,4-dichlorophenyl)-1,3,4-oxadiazolethiol in the presence of diethyl chlorothiophosphate
(DCTP) in good yield.
Table 1 Preparation of amides R1CONR2R3, 4 from amines
Activation of a carbonyl group under mild conditions is
a
challenging, current problem in organic synthesis.
mp/bp
(T/8C)
Yield
(%)
Triphenylphosphine,1 diphenylphosphenyl azide,2 N,N-bis-
(2-oxo-3-oxazolidinyl)phosphorodiamidic chloride,3 diethyl-
phosphorobromidate,4 phenyl N-phenyl phosphoramido-
Entry R1
R2
R3
1
2
3
Ph
Ph
Ph
Ph
oClC6H4
pCO2HC6H4
H
H
H
163
95
90
89
83
chloridate,5
2-sulfanyl
benzoxazole,6
3,6-diethyl-2-
278
(dec.)
158
166
138
162
161
277
138
160
158
179
Liquid
hydroxypyrazine,7 2-chloro-4,6-disubstituted-1,3,5-triazine8
and other organophosphorus reagents9,10 have been used
as acyl-transfer reagents. All these methods require either
expensive reagents or strong reaction conditions and tedious
work-up procedures. For example, Hossain and Borthakur9
used O,O-diethyl dithiophosphoric acid for the acylation of
amines where the reaction was carried out by boiling under
re¯ux a mixture of carboxylic acid, O,O-diethyl dithiophos-
phoric acid and a suitable amine in solvents such as toluene
for several hours. In addition, some of these reactions
are associated with undesired side products, such as urea
derivatives. For example, carbodiimides5 have been used as
condensing agents in the synthesis of carboxamides from
carboxylic acids and amines. The formation of N-acylureas
and anhydrides as side products renders the isolation of
the desired carboxamides dicult.
4
5
Ph
Ph
p-MeOC6H4
o-OHC6H4
Ph
p-MeC6H4
p-BrC6H4
pCO2HC6H4
oClC6H4
p-MeOC6H4
pClC6H4
Ph
H
H
H
H
H
H
H
H
86
85
86
87
86
81
82
83
80
80
76
6
7
8
9
10
11
12
13
14
2,4-Cl2C6H3
2,4-Cl2C6H3
2,4-Cl2C6H3
2,4-Cl2C6H3
2,4-Cl2C6H3
2,4-Cl2C6H3
2,4-Cl2C6H3
Ph
H
Ph
Ph
Ph
Ph
5-(2,4-dichlorophenyl)-2-acyloxy-1,3,4-oxadiazole
acyldiethyl thiophosphate
3
from
and 5-(2,4-dichlorophenyl)-
1
1,3,4-oxadiazolethiol 2, respectively, and their subsequent
ammonolysis.
We report here that 5-(2,4-dichlorophenyl)-1,3,4-oxadi-
azolethiol11 in the presence of diethyl chlorothiophosphate
(DCTP) results in selective acylation of anilines in very
good yield (>80%) at room temperature. The thiol trans-
fers the acyl function from the acyl diethylthiophosphate 1
formed in situ by the reaction of carboxylic acid and diethyl
chlorothiophosphate in the presence of triethylamine at room
temperature. In the case of secondary amines, acylation
could be accomplished only at an elevated temperature
(80±85 8C).
It is to be noted that the method has been applied to the
reaction between anilines and benzoic acids. This is a one-
pot reaction with a very simple work-up procedure. This
ecient procedure for one-pot acylation of amines probably
consists of two reactions; the formation of the active esters,7
Experimental
Mps were recorded in open capillaries in a Buchi apparatus
and are uncorrected. IR spectra were recorded in
Elmer 237 B spectrometer. The 1H NMR spectra were recorded
on Varian T-60 (60 MHz) NMR spectrometer with Me4Si
a Perkin-
a
internal standard. Mass spectra of the compounds were recorded
on a Finnigan-MAT mass spectrometer. The purity of the com-
pounds was checked by TLC using light petroleum±ethyl acetate
(3:2) as eluent and the spots were visualised in iodine or KMnO4
solution.
Preparation of Benzanilide 4.ÐIn a typical experiment benzoic
acid (1.22 g, 0.01 mol), triethylamine (1.52 g, 0.015 mol) and DCTP
(2.82 g, 0.01 mol) were mixed in 25 ml of acetonitrile. The reaction
mixture became turbid owing to the formation of triethylamine
hydrochloride. The mixture was then stirred magnetically for 3 h at
Scheme 1
*To receive any correspondence.
room temperature. To this was added 5-(2,4-dichlorophenyl)-1,3,4-
oxadiazolethiol (2.46 g, 0.015 mol) and the resultant mixture was
kept overnight after stirring for 1 h. Then aniline (1.39 g, 0.015 mol)
was added and stirred for another 0.5 h. After removal of the
$This is a Short Paper as de®ned in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there-
fore no corresponding material in J. Chem. Research (M).
Goswami
