Zinc promoted convenient and general synthesis of thiol esters

Article abstract of DOI:10.1055/s-1998-1797

Synthesis of thiol esters from acyl chlorides and thiols in the presence of activated zinc is described. The recovery of zinc and its reuse makes the procedure more economic.

Full text of DOI:10.1055/s-1998-1797

August 1998
SYNLETT
877
Zinc Promoted Convenient and General Synthesis of Thiol Esters
*
H.M.Meshram, Gondi Sudershan Reddy, K. Hima Bindu and J.S.Yadav
Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 23 May 1998
Abstract : Synthesis of thiol esters from acyl chlorides and thiols in the
presence of activated zinc is described. The recovery of zinc and its
reuse makes the procedure more economic.
1
Thiol ester is an important functional group in organic synthesis. It is
used in the formation of carbon carbon bonds and other functionalities.
Because of the growing importance of thiol esters, various improved
methods have been developed for their direct preparation from
2
carboxylic acids. This protocol requires essentially the activation of
2a
acid. There are numerous activating agents like trisalkylthioborane,
2b
2c
phenyl
dichlorophosphonate,
tri-n-butylphosphine,
diethyl
Convertion of
2d
phosphorocynidate or diphenyl phosphorazidate.
amides to thiol esters using aluminium thiophenoxide or
2e
2f
boronthiophenoxide is also known. Very recently, phosgene is also
used for the preparation of thiol esters. All these existing reagents are
very expensive and procedure requires tedious workup or sometimes
isolation of intermediates. So still there is a scope to search for a new
3a
and inexpensive reagent. Some of the methods using NBS, and N-
3b
methylbenzene thiazolium trifluoromethanesulfonate proceed through
3c,3d
the intermediacy of acid chloride.
This observation and our interest
in the development of new methodologies prompted us to make an
elegant synthesis of thiol ester from acyl chloride. Recently metal
4
catalysed reactions have gained wide prosperity in organic synthesis
because of their simple workup, activating, catalysing nature and
10
selectivity. Among the transition metals zinc catalyst has gained wide
acceptance due to the unique property of surface co-ordination with
polar groups.
Scheme
In our recent study we have demonstrated zinc promoted facile
6
7
esterification of acid chlorides with alcohols, Friedel Crafts’acylation,
8
9
10
carbamate, amide and acylation of ylides. Herein, we wish to report
a mild and general method for the synthesis of thiol esters from acid
chlorides and thiols in the presence of activated zinc (scheme).
organic layers were washed with NaHCO solution (10%, 50 ml) water
3
and dried over Na SO . Evaporation of the solvent gives esters in good
2
4
yields and high purity.
Thiol is added to an anhydrous toluene suspension of acid chloride and
zinc at room temperature. The reaction is spontaneous and after few
minutes it is filtered. The filtrate after aqueous workup gives the thiol
esters in high yields (results are summarized in the tables). We presume
that the electrophilic character of acyl chloride is enhanced by the zinc
which undergoes nucleophilic displacement with respective thiols. The
efficacy of the reaction can be explained by the fact that the polar groups
complex efficiently to the surface of the zinc and thereby increase the
electrophilic character of acyl group. The detailed mechanistic aspects
of the reaction are under investigation.
The reaction is slow when both the reactants are aromatic (entry 1,
table-1). However in case of both aliphatic reactants, the reaction
completes in few minutes. But the extension of acyl group length by one
carbon atom (changes the nature of compound from aromatic to
aliphatic) makes the reaction very facile (entry 9, table-1). Further, we
have observed that the reaction of thiophenol and aliphatic acid
chlorides is very fast but in reverse case reaction proceeds very slowly.
As can be seen from the table, the method is applicable for the
preparation of a wide variety of thiol esters including long alkyl chain, t-
butyl and olefins which supports the generality of the procedure. The
importance of the method is further strengthened by the formation of
thiol ester of aromatic diacid. A separate experiment of 4-chlorobenzoyl
chloride and thiophenol in the absence of zinc does not yield thiol ester.
Though the reaction proceeds with 0.5 eq of zinc, the rate of the reaction
is enhanced by employing 1 eq of zinc. It is important to note that the
unused zinc is recovered at the end of the reaction, which can be reused
again after activation.
11
The preparation of phenyl, 4-chlorobenzothioate (Entry 1, Table-1) is
representative of the general procedure employed. Thus, in a typical
procedure, a mixture of 4-chlorobenzoyl chloride (10 mmol) in toluene
(20 ml) and activated zinc dust (10 mmol) was stirred for 10 minutes.
Then the toluene solution of thiol (10 mmol in 20 ml) was added and
stirring continued for given time (see table). The progress of the reaction
was monitored by tlc. After completion of the reaction, the mixture was
filtered and the solid was washed with ether (100 ml). Combined

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LETTERS
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Acknowledgement: Two of the Authors (GSR, KHB) are thankful for
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