A Convenient Synthesis of Thioacetates and Thiobenzoates Using Silica-Gel Supported Potassium Thioacetate

Article abstract of DOI:10.1081/SCC-120025193

A simple and efficient procedure has been developed for the synthesis of thioesters by a reaction of alkyl halides with silica-gel supported potassium thioacetate or thiobenzoate under mild conditions.

Full text of DOI:10.1081/SCC-120025193

This article was downloaded by: [Moskow State Univ Bibliote]
On: 13 February 2014, At: 01:50
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House,
37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
A Convenient Synthesis of Thioacetates and
Thiobenzoates Using Silica-Gel Supported Potassium
Thioacetate
a
a
b
Tadashi Aoyama , Toshio Takido & Mitsuo Kodomari
a
Department of Materials and Applied Chemistry , College of Science and Technology ,
Nihon University , Kanda Surugadai, Chiyoda-ku, Tokyo, Japan
b
Department of Applied Chemistry , Shibaura Institute of Technology , Shibaura, Minato-ku,
Tokyo, Japan
Published online: 16 Aug 2006.
To cite this article: Tadashi Aoyama , Toshio Takido & Mitsuo Kodomari (2003) A Convenient Synthesis of Thioacetates and
Thiobenzoates Using Silica-Gel Supported Potassium Thioacetate, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 33:21, 3817-3824, DOI: 10.1081/SCC-120025193
To link to this article: http://dx.doi.org/10.1081/SCC-120025193
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained
in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the
Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and
should be independently verified with primary sources of information. Taylor and Francis shall not be liable for
any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever
or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of
the Content.
This article may be used for research, teaching, and private study purposes. Any substantial or systematic
reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any
form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://
www.tandfonline.com/page/terms-and-conditions

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©
2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
Õ
SYNTHETIC COMMUNICATIONS
Vol. 33, No. 21, pp. 3817–3824, 2003
A Convenient Synthesis of Thioacetates and
Thiobenzoates Using Silica-Gel Supported
Potassium Thioacetate
1
,
1
2
Tadashi Aoyama, * Toshio Takido, and Mitsuo Kodomari
1
Department of Materials and Applied Chemistry,
College of Science and Technology, Nihon University,
Kanda Surugadai, Chiyoda-ku, Tokyo, Japan
2
Department of Applied Chemistry, Shibaura Institute
of Technology, Shibaura, Minato-ku, Tokyo, Japan
ABSTRACT
A simple and efficient procedure has been developed for the synthesis
of thioesters by a reaction of alkyl halides with silica-gel supported
potassium thioacetate or thiobenzoate under mild conditions.
*Correspondence: Tadashi Aoyama, Department of Materials and Applied
Chemistry, College of Science and Technology, Nihon University, Kanda
Surugadai, 1-8-14 Kanda Surugadai, Chiyoda-ku, Tokyo 101-8308, Japan;
E-mail: aoyama@chem.cst.nihon-u.ac.jp.
3
817
DOI: 10.1081/SCC-120025193
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©
2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
3818
Aoyama, Takido, and Kodomari
Key Words: Thioester; Potassium thioacetate; Thioacetates;
Thiobenzoates; Silica-gel.
Thioesters are very important compounds in organic synthesis. For
1]
example, thioesters have been employed as mild acyl transfer reagents,
[
[
building blocks of heterocyclic compounds, for aldol reactions and
2]
[3]
[
for the synthesis of ketones and amides, and precursors of thiols.
4]
[5]
[6]
Various synthetic procedures for synthesis of thiosters has been reported
in the literature. Usually thioesters are prepared from the reaction of
[
disulfides with carboxylic acid anhydrides, the reaction of carboxylic
7]
[8]
[9]
acids with thiols, thioacetic acids with alcohols, and organic halides
[
10]
with potassium thioacetate in polar solvents. These reactions are very
efficient, but vigorous conditions, long reaction times and the use of
environmentaly unfriendly reagents such as metal halides are often
necessary to promote the reactions. The reaction of alkyl halides with
potassium thioacetate in a nonpolar solvent did not proceed at all since
the potassium thioacetate is insoluble in a nonpolar solvent. Therefore,
the reaction of alkyl halides with potassium thioacetate should be carried
out in a polar solvent such as ethanol or dimethyl formamide. Supported
reagents are attractive in organic synthesis in view of their higher selec-
tivity, milder reaction conditions, easier work-up, and environmentaly
friendly reactions. Recently, many reactions using supported reagents
have been reported. We have found that potassium thioacetate can be
activated remarkably by supporting onto silica-gel, and silica-gel
supported potassium thioacetate (AcSK/SiO ) reacts with alkyl halides
2
in nonpolar solvents such as benzene to give alkyl thioacetates in good
yields. Herein we report a convenient procedure for the conversion of
alkyl halides 1 into alkyl thioacetate 2 by using AcSK/SiO (Sch. 1).
2
Benzyl bromide did not react with finely ground potassium
thioacetate suspended in benzene at room temperature. In contrast,
similar reaction with AcSK/SiO proceeded easily under similar con-
2
ditions to afford benzyl thioacetate in 83% yield after 1 h. As shown in
Table 1, silica-gel was the most effective among the inorganic supports
tested. Alumina was also effective but less than silica-gel. Molecular
sieves 4A was much less effective. Celite and Montmorillonite K10
were ineffective for activating potassium thioacetate.
Scheme 1.

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©
2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
Silica-Gel Supported Potassium Thioacetate
3819
Table 1. Comparative effectiveness of various supports for
a
thioesterification of benzyl bromide using AcSK/support .
Support
Yield/(%)
None
no reaction
no reaction
no reaction
Montmorillonite K10
Celite
MS-4A
trace
53
48
Neutral-Al
Acidic-Al
Basic-Al O3
2 3
O
2
O
3
33
83
2
Silica-gel
a
A mixture of benzyl bromide (1 mmol) and AcSK/support (1 mmol,
1 g) in benzene (5 mL) was stirred at r.t. for 1 h. Yields were
determined by GLC.
The reaction of a series of organic halides with AcSK/SiO2 in
benzene gave the corresponding thioacetates in high yields. The reaction
of benzyl chloride with AcSK/SiO required more strong conditions than
2
that of benzyl bromide. Substituted benzyl halides were converted into
the corresponding thioacetates in excellent yields at room temperature
independent of the substituent (2a–e). For instance, 4-methyl and
4
-nitrobenzyl bromide were converted into the corresponding
thioacetates in 98 and 97% yields. Xylylene dibromides produced only
disubstituted compound (2f–h). Mono substituted compound were not
detected (Table 2).
Although the reaction with n-alkyl halides did not proceed at room
ꢀ
temperature, when the reaction temperature was increased to 80 C the
reactions occurred to give the corresponding thioacetates. The reactivity
of n-alkyl halides decreased as follow; I>Br>Cl (See Table 3). Octyl
thioacetate was obtained quantitatively from octyl iodide after 3 h,
whereas, octyl chloride gave only 32% yield of octyl thioacetate after
2
halides. 2-Bromooctane was converted to corresponding thioacetate at
4 h. Secondary alkyl halides were less reactive than primary alkyl
ꢀ
8
0 C, but the yield was only 26% after 24 h. In the case of 1,4-dibromo-
pentane, 4-Bromopentyl thioacetate was formed along with a small
amount of disubstituted compound, but 4-bromo-1-methylbutyl
thioacetate was not detected. The other bromides such as allylic bromides
and a-bromoketones were also converted into the corresponding

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©
2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
3820
Aoyama, Takido, and Kodomari
Table 2. Synthesis of thioesters from substituted benzyl halides and
a
AcSK/SiO
R-X
2
.
b
Temp./ Time/ Yield /
ꢀ
Products
( C)
(h)
(%)
2
2
2
a
a
b
50
3
90
r.t.
r.t.
r.t.
r.t.
r.t.
1
1
1
1
1
91
98
97
97
99
2
c
2
d
2
e
c
2
f
r.t.
r.t.
1
1
91
c
96
2
2
g
h
c
94
r.t.
1
a
A mixture of substituted benzyl halide (5 mmol) and AcSK/SiO2 (7.5 mmol,
7.5 g) in benzene (20 mL) was stirred and then filtered to remove the used
supported reagents. The filtrate was evaporated to afford the product.
b
Yield of isolated and purified (>98%) product.
AcSK/SiO (15 mmol, 15 g) and benzene (40 mL) were used.
c
2
thioacetates at room temperature. Ethyl 2-bromopropionate required 3 h
to complete the reaction, and afford the corresponding thioacetate in 84%
yield. In contrast, a-bromobenzyl phenyl ketone produced 2-oxo-1,
2
-diphenylethyl thioacetate in 72% yield in 1 h, and small amount of
unexpected product, benzyl phenyl ketone, was formed along with the
thioacetate. Using silica-gel supported potassium thiobenzoate

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©
2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
Silica-Gel Supported Potassium Thioacetate
3821
a
Table 3. Synthesis of thioesters from alkyl halides and AcSK/SiO2.
b
Temp./
ꢀ
Time/
(h)
Yield /
(%)
R-X
Products
( C)
c,d
2
2
2
2
i
i
i
j
80
80
80
80
24
8
32
c,d
89
d
100
3
c,d
26
24
e
75 (11)
f
2
k
60
7
5
c
85
2
l
r.t.
2
m
r.t.
r.t.
1
1
76
82
2
n
2
o
p
r.t.
r.t.
1
1
96
92
2
2
q
r.t.
3
84
91
2
2
r
s
r.t.
r.t.
1
1
c
72 (19)
g
a
A mixture of alkyl halide (5 mmol) and AcSK/SiO (7.5 mmol, 7.5 g) in benzene
2
(20 mL) was stirred and then filtered to remove the used supported reagents. The
filtrate was evaporated to afford the product.
b
Yield of isolated and purified (>98%) product.
The product was isolated with column chromatography.
c
d
2
AcSK/SiO (10 mmol, 10 g) and benzene (25 mL) were used.
e
AcSK/SiO (15 mmol, 15 g) and benzene (40 mL) were used.
2
f
Yield of disubstituted compound.
Yield of benzyl phenyl ketone.
g

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©
2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
3822
Aoyama, Takido, and Kodomari
a
Table 4. Synthesis of thiobenzoate from alkyl bromides and PhCOSK/SiO2.
b
Temp./ Time/ Yield /
ꢀ
R-Br
Products
( C)
(h)
24
4
(%)
c
52
3
3
3
a
a
b
80
c
94
80
r.t.
1
99
d
100
3
c
r.t.
1
3
d
r.t.
r.t.
1
1
100
98
3
e
3
f
r.t.
1
98
a
2
A mixture of alkyl bromide (5 mmol) and PhCOSK/SiO (7.5 mmol, 7.5 g) in
benzene (20 mL) was stirred and then filtered to remove the uesd supported
reagents. The filtrate was evaporated to afford the product.
b
Yield of isolated and purified (>98%) product.
c
2
PhCOSK/SiO (10 mmol, 10 g) and benzene (25 mL) were used.
d
PhCOSK/SiO (15 mmol, 15 g) and benzene (40 mL) were used.
2
(PhCOSK/SiO ), the reaction rapidly occurred at room temperature to
2
give the corresponding thiobenzoates in high yields (See Table 4). The
reactivity of PhCOSK/SiO was higher than AcSK/SiO . Octyl bromide
reacted with AcSK/SiO to afford the octyl thioacetate in 89% yield
2
2
2
ꢀ
at 80 C after 8 h, whereas, the reaction with PhCOSK/SiO gave octyl
2
thiobenzoate (3a) in 94% yield after 4 h. Moreover, octyl chloride gave 3a
in 52% yield after 24 h.
In conclusion, the present procedure using silica-gel supported
potassium thioacetate and thiobenzoate allows for an efficient transforma-
tion of organic halides into thioesters. The notable advantages of this
procedure are: operational simplicity, good yield, and mild reaction
conditions. Moreover, the products are easily isolated by filtering the

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©
2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
Silica-Gel Supported Potassium Thioacetate
3823
used supported reagent and removing the solvent under vacuum, and are
generally spectroscopically pure.
EXPERIMENTAL
Preparation of supported reagent AcSK/SiO : Silica-gel supported
2
potassium thioacetate was prepared as follows. Silica-gel (Wakogel
C-200(Wako pure chemical ind. Ltd.), 8.86 g) was added to a solution
of potassium thioacetate (10 mmol, 1.14 g) in methanol, and the mixture
was stirred at room temperature for 0.5 h. The methanol was removed by
rotary evaporator under reduced pressure, and the resulting reagent was
dried in vacuo (10 mmHg) at room temperature for 1 h.
In a typical procedure, a mixture of benzyl bromide (5 mmol) and
AcSK/SiO (7.5 mmol, 7.5 g) was stirred in benzene at room temperature
2
for 1 h, and then filtered to remove the uesd supported reagents. The
filtrate was evaporated to afford the product, benzyl thioacetate, in
9
1% yield, and the purity was >99%.
ꢁ
b. liquid; IR(neat): 1691 cm . H NMR(CDCl ) ꢀ 2.31 (3H, s), 2.33
3
1 1
2
(
3H, s), 4.08 (2H, s), 7.10 (2H, d, J ¼ 8Hz), 7.17 (2H, d, J ¼ 8Hz).
þ
MS(EI). m/z ¼ 180(M ).
ꢀ
ꢁ1
1
2
d. M.p. 53–54 C. IR(KBr): 2233, 1685 cm
.
H NMR(CDCl3)
ꢀ
2.37 (3H, s), 4.13 (2H, s), 7.41 (2H, d, J ¼ 8Hz). 7.59 (2H, d, J ¼ 8Hz).
þ
MS(EI) m/z ¼ 191(M ).
ꢀ
ꢁ1
1
r. M.p. 43–44 C. IR(KBr): 1695, 1684 cm . H NMR(CDCl ) ꢀ
2
3
2
7
.41 (3H, s), 4.41 (2H, s), 7.48 (2H, t, J ¼ 8Hz), 7.60 (1H, d, J ¼ 8Hz),
þ
.99 (2H, d, J ¼ 8Hz). MS(EI) m/z ¼ 194(M ).
ꢀ
ꢁ1 1
c. M.p. 52–53 C. IR(KBr): 1662 cm . H NMR(CDCl ) ꢀ 4.30 (4H,
3
3
s), 7.27 (3H, m), 7.38 (1H, s), 7.43 (4H, t, J ¼ 8Hz), 7.56 (2H, d, J ¼ 8Hz),
þ
7
.96 (4H, d, J ¼ 8Hz). MS(EI) m/z ¼ 378(M ).
ꢀ
[11]
ꢀ
ꢁ1
3
f. M.p. 84–85 C (Lit.
79–80 C). IR(KBr): 1697, 1657 cm .
1
H NMR(CDCl ) ꢀ 4.59 (2H, s), 7.46 (2H, t, J ¼ 8Hz), 7.50 (2H, t,
3
J ¼ 8Hz), 7.59 (1H, t, J ¼ 8Hz), 7.61 (1H, t, J ¼ 8Hz), 8.00 (2H, d,
þ
J ¼ 8Hz), 8.07 (2H, d, J ¼ 8Hz). MS(EI) m/z ¼ 256(M ).
REFERENCES
1
. Mukaiyama, T.; Araki, M.; Takei, H. Reaction of S-(2-pyridyl)
thioates with grignard reagents. A convenient method for the pre-
paration of ketones. J. Am. Chem. Soc. 1973, 95, 4763–4765.

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©
2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
3824
Aoyama, Takido, and Kodomari
2
. Annunziata, R.; Benaglia, M.; Cinquini, M.; Cozzi, F.
Enantioselective one-pot synthesis of ꢁ-lactams from achiral 2-
pyridylthioesters and aromatic imines. Tetrahedron Lett. 1995, 36,
6
13–616.
3
. Mukaiyama, T.; Uchiro, H.; Shiina, I.; Kobayashi, S. Facile
synthesis of optically active anti-a,b-dihydroxy ester derivatives.
Chem. Lett. 1990, 1019–1022.
4
. McGarveym, G.J.; Williams, J.M.; Hiner, R.N.; Matsubara, Y.;
Oh, T. L-Aspartic acid in acyclic stereoselective synthesis.
Synthetic studies on amphotericin B. J. Am. Chem. Soc. 1986,
1
08, 4943–4952.
5
. Davis, A.P.; Walsh, J.J. Amide bond formation via pentafluorothio-
phenyl active esters. Tetrahedoron Lett. 1994, 35, 4865–4868;
Davis, A.P.; Menzer, S.; Walsh, J.J.; Williams, D.J. Steroid-based
receptors with tunable cavities; a series of polyhydroxylated
macrocycles of varying size and flexibility. Chem. Commun. 1996,
4
53–455.
6
. Dudek, S.P.; Sikes, H.D.; Chidsey, C.E.D. Synthesis of
ferrocenethiols containing oligo(phenylenevinylene) bridges and
their characterization on gold electrodes. J. Am. Chem. Soc. 2001,
1
23, 8033–8038; Bodwell, G.J.; Birdson, J.N.; Chen, S.-L.;
Poirier, R.A. Nonplanar aromatic compounds. 5. A atrategy for
the synthesis of cis-10b,10c-dimethyl-10b,10c-dihydropyrenes. First
crystal structure of a cis-10b,10c-dimethyl-10b,10c-dihydropyrene.
J. Am. Chem. Soc. 2001, 123, 4704–4708.
7
8
9
. Movassagh, B.; Lakouraj, M.M.; Fadaei, Z. A convenient one-pot
synthesis thiol esters from disulfides using a Zn/AlCl system. J.
Chem. Research(S) 2001, 22–23.
. Iimura, S.; Manabe, K.; Kobayashi, S. Direct thioesterification
from carboxylic acid and thiols catalyzed by a bronsted acid.
Chem. Commun. 2002, 94–95.
3
. Gauthier, J.Y.; Bourdon, F.; Young, R.N.A Mild and efficient
synthesis of thiolesters from alcohols. Tetrahedron Lett. 1986, 27,
1
5–18.
1
1
0. Zheng, T.; Burkart, M.; Richardson, D.E. A general and mild
synthesis of thioesters and thiols from halides. Tetrahedron Lett.
1
999, 40, 603–606.
1. Allan, W. 2-Heterosubstituted silylated ketone acetals: reagents for
the preparation of a-functionalized methylketones from carboxylic
acid chlorides. J. Org. Chem. 1979, 44 (25), 4617–4622.
Received in the UK May 17, 2003