Convenient and efficient synthesis of thiol esters using zinc oxide as a heterogeneous and eco-friendly catalyst

Article abstract of DOI:10.1071/CH08202

A catalytic method was developed to synthesize thiol esters from the reaction of acyl chlorides and thiols using zinc oxide as a catalyst under solvent-free conditions at room temperature. Mild reaction conditions, short reaction time, excellent yields of products and recyclability of the catalyst are noteworthy features of this methodology. CSIRO 2008.

Full text of DOI:10.1071/CH08202

Short Communication
CSIRO PUBLISHING
Aust. J. Chem. 2008, 61, 1006–1010
www.publish.csiro.au/journals/ajc
Convenient and Efficient Synthesis of Thiol Esters using
Zinc Oxide as a Heterogeneous and Eco-Friendly Catalyst
Babasaheb Pandurang Bandgar,A,B Parmeshwar Eknath More,A
Vinod Tribhuvannathji Kamble,A and Sanjay Suresh SawantA
AOrganic Chemistry Research Laboratory, School of Chemical Sciences, Swami Ramanand Teerth
Marathwada University, Vishnupuri, Nanded-431606 MS, India.
BCorresponding author. Email: bandgar_bp@yahoo.com
A catalytic method was developed to synthesize thiol esters from the reaction of acyl chlorides and thiols using zinc oxide
as a catalyst under solvent-free conditions at room temperature. Mild reaction conditions, short reaction time, excellent
yields of products and recyclability of the catalyst are noteworthy features of this methodology.
Manuscript received: 12 May 2008.
Final version: 4 August 2008.
Thiol esters are used in the formation of carbon–carbon
bonds and other functionalities. In addition, they show
higher reactivity and selectivity towards nucleophiles than
the corresponding oxygen analogue, which makes them the
universal acylation reagents in biochemical processes. These
compounds were traditionally synthesized from the reaction
of carboxylic acids and thiols.[1] A problem associated with
this synthetic method is that the reaction requires essen-
tially the activation of an acid. A variety of activating agents
such as trisalkylthioborane,[1a] phenyl dichlorophosphonate,[1b]
tri-n-butylphosphine,[1c] diethyl phosphorocyanidate[1d] and
triphenylphosphine N-bromo succiniamide/N-iodo succini-
amide,[1e] and phosgene[1f] have been reported for this purpose.
Preparation of thiol esters from the reaction of amides and
thiols using aluminium thiophenoxide or boron thiophenoxide
are also reported in the literature.[1g] Some other methods using
N-methylbenzene thiazolium trifluoromethane sulfonate,[2a]
zinc[2b] and thallium[2c,2d] and tin[2e] or copper mercaptides[2f]
proceed through the intermediacy of an acid chloride.[2f,2g] All
these reported methods have one or other disadvantage, such
as the use of expensive reagents,[1b–1d,2a,2f] tedious workup
procedures,[1a–1f,2a,2f] toxic or hazardous reagents,[1e,1f] and
sometimes difficult isolation of intermediates.[1e] In recent
years, cyanuric chloride,[3a] and Dess–Martin periodinane[3b]
have been reported to catalyze this reaction.
O
O
ZnO
r.t.
C
SR2
R2
R1
R1
Cl
C
SH
ϩ
1
2
3
R1 ϭ alkyl, aryl R2 ϭ alkyl, aryl
Organic chemists continue to explore novel synthetic meth-
ods involving new reagents and catalysts to carry out chemical
Scheme 1.
SH
CH3COCl
SCOCH3
CH3OCO
SH
HO
HO
ϩ
ZnO, r.t., neat
98%
0%
O
O
C
O
C
CH3
S
CH3
SH
OH
CH3COCl
ϩ
ϩ
ZnO, r.t., neat
0%
98%
O
O
SH
NH2
NH C CH3
S
C
CH3
CH3COCl
ϩ
ϩ
ZnO, r.t., neat
0%
97%
Scheme 2.
© CSIRO 2008
10.1071/CH08202
0004-9425/08/121006

Synthesis of Thiol Esters
1007
transformations. One of these novel synthetic methods is to
carry out reactions on the surface of solids. Organic reactions
were found to occur efficiently and selectively on the surface
of solids.[4] Even in the absence of new chemistry, a surface
reaction may be more desirable than a solution counterpart,
because the reaction is more convenient to run, or a high yield
of product is attained. Reactions on surfaces of solids have some
advantages, such as: (i) easy isolation of products; (ii) high
yields of products and suppression of by-product formation; and
(iii) improved selectivity of catalyst.
In recent years, zinc oxide has gained much interest in
the synthesis of nitriles from aldoximes,[5] the Beckmann
rearrangement,[6] Friedel–Crafts acylation,[7] and the acyla-
tion of alcohols, phenols, and amines.[8] Herein, we describe
a new, simple, and effective procedure for the synthesis of thiol
esters from acid chlorides and thiols in the presence of zinc
oxide as a heterogeneous catalyst under solvent-free condition
(Scheme 1).
A mixture of acid chloride, thiol and zinc oxide was stirred
at room temperature. Although the reactions were monitored by
TLC, visual monitoring was possible for these reactions: imme-
diately after the addition of the catalyst to the mixture of the
acid chloride and thiol, yellow or brown colour started develop-
ing, indicating the progress of the reaction. After completion of
the reaction (TLC), dichloromethane was added to the reaction
mixture and the catalyst was filtered off. The dichloromethane
extract was washed with an aqueous sodium bicarbonate solu-
tion and dried over anhydrous sodium sulfate. Removal of the
solvent under reduced pressure furnished the desired products
in excellent yields. The results are presented in Table 1.
The methodology was found to be general, as both aliphatic as
well as aromatic acid chlorides smoothly reacted with aliphatic
and aromatic thiols, resulting in the formation of the corre-
sponding thiol esters in excellent yields in a short reaction time.
The reactions were remarkably clean and no chromatographic
separation was necessary to get pure products. It is indeed grat-
ifying to note that acylation occurred exclusively at the sulfur
and not on the ring carbon atom. It is also interesting to men-
tion that the reaction conditions are mild enough not to induce
any dealkylation of an ether residue (entry o, Table 1). The
dicarboxylic acid chloride also smoothly converted to the cor-
responding dithiol ester (entry k, Table 1) using two equivalents
of thiol. However, this conversion took a comparatively longer
time (45 min).
Thesuperiorityofthisprotocolcanbeclearlyvisualizedinthe
preparation of thiol esters when both the reactants were aromatic,
furnishing excellent yields of products in a short reaction time
(4–45 min) in the presence of zinc oxide as a catalyst without
any activation. In this connection, it should be mentioned that
the literature-reported method[2b] using a stoichiometric amount
of activated zinc required a longer reaction time (240–300 min).
The feasibility of the reusability and recycling of the zinc
oxide was examined through a series of sequential reactions of
benzoyl choride and thiocresol as a model reaction. In a typical
reaction, the catalyst was recovered by simple filtration from
the reaction mixture and reused for three cycles. The reaction
proceededsmoothlywithayieldof96–90%andthisresultshows
that the catalyst does not lose its activity even after three runs
(Table 2, entries 1–3).
selectively in the presence of alcohols, phenols, and amines
(Scheme 2). The reactions were monitored by TLC. The reac-
tion temperature is an important factor for chemoselectivity and
the best temperature was approximately room temperature.
We have developed a novel, simple, and highly efficient pro-
tocol for the acylation of thiols to furnish thiol esters using
non-toxic and inexpensive zinc oxide as a catalyst under solvent-
free conditions. The advantages of this environmentally benign
and efficient protocol include: simple reaction set-up not requir-
ing specialized equipment, no requirement to activate the cata-
lyst, mild reaction conditions, excellent yields of products, short
reaction times, and high chemoselectivity.
Experimental
Melting points were measured using a Buchi R-535 apparatus.
IR spectra were recorded on a Bomem MB Fourier transform
(FT)-IR spectrometer. 1H NMR spectra were recorded on a
Varian Gemini-300 spectrometer. The catalyst (zinc oxide) was
purchased from Sigma–Aldrich and used without any activation.
General Experimental Procedure
To a stirred mixture of acid chloride (1 mmol) and zinc
oxide powder (0.5 mmol), thiol (1 mmol) was added. The
yellow-brown colour developed immediately and became dark
with the progress of the reaction. Stirring was continued
up to completion of the reaction (TLC). After addition of
dichloromethane (10 mL), zinc oxide was filtered off, and
washed with dichloromethane (3 × 5 mL). The dichloromethane
extract was washed with aqueous sodium bicarbonate and dried
over anhydrous sodium sulfate. Removal of the solvent under
reduced pressure furnished practically pure product.
3a: νmax(KBr)/cm−1 894, 1200, 1666, 2916, 3059. δH
(CDCl3, 300 MHz) 7.28–7.62 (m, 10H).
3b: νmax(KBr)/cm−1 645, 897, 1204, 1668, 2916, 3070. δH
(CDCl3, 300 MHz) 3.39 (s, 3H), 7.22–7.57 (m, 5H), 8.00 (d, J
72, 2H), 8.10 (d, J 7.2, 2H).
3c: νmax(KBr)/cm−1 645, 897, 1204, 1668, 2916, 3070. δH
(CDCl3, 300 MHz) 1.58 (s, 9H), 7.30–7.68 (m, 5H).
3d: νmax(KBr)/cm−1 620, 805, 929, 1473, 1695, 2930, 2966.
δH (CDCl3, 300 MHz) 1.60 (s, 9H), 2.42 (s, 3H), 7.99 (d, J 7.4,
2H), 8.09 (d, J 7.4, 2H).
3e: νmax(neat)/cm−1 620, 746, 1354, 1439, 1709, 2928, 3062.
δH (CDCl3, 300 MHz) 2.40 (s, 3H), 7.28–7.76 (m, 5H).
3f : νmax(neat)/cm−1 615, 746, 1114, 1478, 1708, 3061. δH
(CDCl3, 300 MHz) 2.38 (s, 3H, COCH3), 3.41 (s, 3H), 7.97 (d,
J 7.2, 2H), 8.01 (d, J 7.2, 2H).
3g: νmax(neat)/cm−1 670, 895, 1605, 1680, 2900, 3029. δH
(CDCl3, 300 MHz) 7.21 (s, 5H, ArH), 7.40 (s, 5H, ArH), 7.50
(d, 1H, J 16.2, =CH), 7.62 (d, 1H, J 16.2, =CH).
3h: νmax(neat)/cm−1 690, 880, 1609, 1675, 2917, 3060. δH
(CDCl3, 300 MHz) 2.30 (s, 3H, Ar–CH3), 7.10 (s, 5H, Ar–H),
7.40 (d, 1H, J 15.5, =CH), 7.55 (d, 1H, J 15.5, =CH), 7.85 (d,
2H, J 7.4, ArH), 7.90 (d, 2H, J 7.4, ArH).
3i: νmax(KBr)/cm−1 720, 916, 1171, 1588, 1665, 2970, 3035.
δH (CDCl3, 300 MHz) 7.03–7.52 (m, 5H), 7.90 (d, J 8.5, 2H),
8.02 (d, J 8.5, 2H).
3j: νmax(KBr)/cm−1 740, 925, 1170, 1603, 1670, 2960, 3040.
δH (CDCl3, 300 MHz) 2.30 (s, 3H, ArCH3), 7.69 (d, J 8.5, 2H),
7.76 (d, J 8.5, 2H), 7.95 (d, J 7.4, 2H), 8.01 (d, J 7.4, 2H).
3k: νmax(KBr)/cm−1 751, 845, 1240, 1669, 1690, 2930, 3061.
δH (CDCl3, 300 MHz) 7.21–7.54 (s, 10H, ArH), 7.85 (s, 4H,
ArH).
Further, we investigated the possible chemoselectivity of zinc
oxide-mediated acylation reactions by running the competitive
acetylation of alcohols, phenols, amines, and thiols at room tem-
perature over 25 min. It was found that thiols were acylated

1008
B. P. Bandgar et al.
Table 1. Zinc oxide-catalyzed synthesis of thiol esters under solvent-free conditions
Entry
Acid chloride
Thiol
Product
Time
[min]
Yield
[%]
mp
[◦C]
O
S
COCl
SH
a
05
05
07
15
07
03
94
56–58
O
SH
S
COCl
b
c
d
e
f
96
96
91
97
93
64
Me
Me
Me
Me
Me
Me
Me
Me
O
C
S
Me3C
Me3C
Me
SH
33–35
O
C
Cl
Cl
Me3C
Me3C
O
C
SH
S
38
O
C
O
C
S
SH
Oil
O
Me
Me
C
Cl
O
C
SH
Me
S
Oil
O
C
Cl
O
C
O
C
SH
g
S
30
87
Semi-solid
Cl
Cl
O
C
O
C
SH
S
h
i
30
35
30
89
81
82
Oil
69
48
Me
Me
O
COCl
COCl
SH
S
Cl
Cl
O
SH
S
j
Cl
Cl
Me
Me
O
SPh
COCl
k
45
90
58–60
SH
PhSC
ClOC
O
(Continued)

Synthesis of Thiol Esters
1009
Table 1. (Continued)
Entry
Acid chloride
Thiol
Product
Time
[min]
Yield
[%]
mp
[◦C]
O
COCl
SH
SPh
l
30
15
80
89
98
O2N
O2N
O
COCl
m
n
EtSH
EtSH
EtSH
Oil
SEt
O
COCl
25
25
90
90
Semi-solid
Semi-solid
SEt
Cl
Cl
O
COCl
o
SEt
MeO
MeO
SEt
COCl
p
q
EtSH
EtSH
30
4
90
76
76
O
Me3CCOCl
Me3CCOSEt
Oil
O
COCl
r
n-PrSH
10
86
Semi-solid
SPr
3q: νmax(neat)/cm−1 689, 914, 1206, 1448, 1695, 2964, 3067.
δH (CDCl3, 300 MHz) 1.04 (t, J 7.5, 3H), 1.98 (s, 9H), 2.01 (q,
J 7.5, 2H).
Table 2. Reuse studies of zinc oxide for the reaction o-benzoyl chloride
with thiocresol
YieldA
3r: νmax(neat)/cm−1 688, 1175, 1448, 1581, 1689, 2964,
3062. δH (CDCl3, 300 MHz) 1.02 (t, J 7.4, 3H), 1.66–1.72 (m,
2H), 3.04 (t, J 7.3, 2H), 7.40–7.55 (m, 5H, ArH).
No. of uses
Reaction time [min]
1
2
3
10
15
20
96
92
90
Acknowledgement
AYield of pure isolated products.
The authors thank Council of Scientific and Industrial Research, New Delhi,
for financial assistance (project no. 1/2023/05/EMR-II), and P. E. More
thanks University Grant Commission, New Delhi for a teaching fellowship
and S. P. Mahila College, Baramati, for sanctioning study leave.
3l: νmax(KBr)/cm−1 742, 850, 1220, 1670, 2918, 3062. δH
(CDCl3, 300 MHz) 7.31–7.58 (m, 5H, ArH), 7.92 (d, J 7.0, 2H),
8.03 (d, J 7.0, 2H).
References
3m: νmax(neat)/cm−1 690, 913, 1208, 1448, 1663, 2929,
3062. δH (CDCl3, 300 MHz) 1.35 (t, J 7.4, 3H), 3.08 (q, J 7.4,
2H), 7.41–7.56 (m, 5H, ArH).
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