Convenient synthesis of thiol esters from acyl chlorides and disulfides using Zn/AlCl3

Article abstract of DOI:10.1007/s007060200078

Various thiol esters were prepared by condensation of acyl chlorides with disulfides in the presence of Zn/AlCl₃. The advantages of this method are high yields under relatively mild conditions, simple work-up, lack of toxicity, and low costs.

Full text of DOI:10.1007/s007060200078

Monatshefte f uÈ r Chemie 133, 1085±1088 ꢀ2002)
Convenient Synthesis of Thiol Esters
from Acyl Chlorides and Disul®des
Using Zn=AlCl3
Moslem M. Lakouraj1 , Barahman Movassagh , and Zahra Fadaei2
;Ã
2;Ã
1
Institute of Chemistry, Mazandaran University, Babolsar 47415, Iran
2
Department of Chemistry, Razi University, Kermanshah 67149, Iran
Summary. Various thiol esters were prepared by condensation of acyl chlorides with disul®des in the
presence of Zn=AlCl . The advantages of this method are high yields under relatively mild condi-
tions, simple work-up, lack of toxicity, and low costs.
3
Keywords. Thiol esters; Zn=AlCl ; Reductive cleavage of disul®des.
3
Introduction
Thiol esters have received considerable interest because of their importance as mild
acyl transfer agents and intermediates in organic synthesis [1±5]. Among the large
number of methods available for the synthesis of thiol esters, those which make use
of carboxylic acids or their derivatives as starting materials have been extensively
studied [6±14]. However, these methods implicate toxic and hazardous reagents,
harsh conditions, or uncommon starting materials.
Acid chlorides have been classically transformed to thiol esters by means of
thiols in presence of a base. However, using transition metal mercaptides gives
better yields for this transformation [15±18]. Recently, Zhang et al. have reported
that SmI reduces diphenyl disul®de or thiocyanates to the corresponding samar-
2
ium mercaptides which mildly react with acyl chlorides in nitrogen atmosphere to
produce thiol esters [19±21].
In connection with our previous work on Zn=AlCl which revealed to be an
3
ef®cient reagent for the coupling of disul®des with various halides [22], herein we
wish to report a convenient and ef®cient synthesis of thiol esters from disul®des
and acyl chlorides in acetonitrile.
Results and Discussion
As summarized in Table 1, both aromatic and aliphatic acid chlorides are easily
coupled with both aromatic and aliphatic disul®des. The reaction of acetyl chloride
à Corresponding authors. E-mail: lakouraj@umcc.ac.ir

1
086
M. M. Lakouraj et al.
Table 1. Preparation of thiol esters from disul®des and acid chlorides using Zn=AlCl ; yields refer to
3
pure isolated products
0
Entry
R
R
t=min
Yield=%
Ref.
1
2
3
4
5
6
7
8
9
Ph
CH3
CH3
CH3
CH3
CH3
CH3
CH3
Ph
60
60
65
80
80
90
100
40
40
45
50
55
86
84
85
82
79
80
77
92
92
91
79
78
[18]
[24]
[25]
[26]
[27]
[27]
[28]
[18]
[29]
[25]
[30]
[3]
4-ClC H
6
4
4-CH C H
6
3
4
PhCH2
n-Octyl
n-Butyl
Cyclohexyl
Ph
4-ClC H
6
Ph
4
1
1
1
0
1
2
4-CH C H
3
Ph
6
4
PhCH2
Ph
n-Butyl
Ph
Scheme 1
ꢀ
with various disul®des proceeded quantitatively at 40 C with a molar ratio of
AlCl :acetyl chloride ˆ 1:2; however, the condensation of benzoyl chloride with
3
ꢀ
disul®des required elevated temperatures ꢀ65 C) and a higher quantity of alumi-
num chloride ꢀAlCl :benzoyl chloride ˆ 1:1) for completion. The presence of alu-
3
minum chloride is essential; in the absence of this Lewis acid, the reaction slows
down considerably. When disul®des primarily reacted with Zn=AlCl in aceto-
3
nitrile, the zinc powder almost disappeared during 30±40 minutes. This indicates
that a reductive cleavage of the S±S bond [19] may lead to the zinc thiolate
intermediate which further undergoes nucleophilic displacement with acid chloride
in the presence of AlCl to afford the thiol ester ꢀScheme 1).
3
Experimental
Disul®des were prepared according to the method reported by Rieke et al. [23]. Zinc powder, AlCl3,
and acyl chlorides were purchased from Merck or Fluka. All products were characterized by com-
parison of their spectroscopic and physical data with those of known samples. IR spectra were
1
obtained using a Shimadzu 470 instrument. H NMR spectra were determined by Jeol JNM-PMX
6
0 MHz or Bruker 200 MHz NMR spectrometers.
General procedure for the preparation of thiol esters from acetyl chloride
In a round-bottomed ¯ask equipped with a drying tube, a mixture of disul®de ꢀ0.5 mmol), zinc
powder ꢀ2.0 mmol), and ®nely ground anhydrous aluminum chloride ꢀ1.0 mmol) was suspended in
3
acetonitrile ꢀ7 cm ). The mixture was stirred for 30±40 min at 40 C, during which time the zinc
ꢀ

Thiol Esters from Acyl Chlorides
1087
powder was almost completely consumed. Then, acetyl chloride ꢀ2.0 mmol) was added, and the
mixture was stirred for additional 30±70 min at this temperature. Progress of the reaction was moni-
tored by TLC. The solvent was evaporated, and the residue was washed with 10% NaHCO and H O
3
2
3
3
ꢀ
2 Â 10 cm ) to remove the unreacted acetyl chloride. Extraction with diethyl ether ꢀ3 Â 10 cm ),
drying ꢀMgSO ) of the combined organic layers, and evaporation of the solvent gave the pure thiol
4
ester.
General procedure for preparation of thiol esters from benzoyl chloride
In a round-bottomed ¯ask equipped with a condenser and drying tube, a mixture of disul®de
ꢀ
0.5 mmol), zinc powder ꢀ2.0 mmol), ®nely ground anhydrous aluminum chloride ꢀ2.0 mmol), and
3
ꢀ
acetonitrile ꢀ7 cm ) was stirred at 65 C. When the zinc powder had almost disappeared ꢀ30±40 min),
benzoyl chloride ꢀ2.0 mmol) was added, and the resulting mixture was stirred for additional 10±
2
0 min. After completion of the reaction, the solvent was evaporated in vacuo, and the residue was
3
extracted with diethyl ether ꢀ2 Â 10 cm ). The combined organic layers were dried over MgSO .
4
Evaporation of the solvent gave the desired thiol esters in 78±92% yield. In some cases ꢀTable 1,
entries 8±10) the thiol esters were recrystallized from EtOH.
Acknowledgments
The authors are grateful to the Razi University Research Council for ®nancial support and to the
Institute of Chemistry of Mazandaran University for complementary assistance of this work.
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Received July 20,2001. Accepted September 24,2001