Phase transfer catalysis in solid-liquid system as a selective method of mono-alkylation of α-sulfonyl thioesters

Article abstract of DOI:10.1081/SCC-120004136

α-Phenylsulfonyl methylthioacetate gave monoalkylated products in high yields when treated with alkyl halides in the presence of K₂CO₃ with TEBAC in CH₂Cl₂, at r.t. The superiority of this method over that in th

Full text of DOI:10.1081/SCC-120004136

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
PHASE TRANSFER CATALYSIS IN SOLID–LIQUID
SYSTEM AS A SELECTIVE METHOD OF MONO-
ALKYLATION OF α-SULFONYL THIOESTERS
Blanka Wladislaw , Liliana Marzorati , Regina M. A. Neves & Claudio Di Vitta
To cite this article: Blanka Wladislaw , Liliana Marzorati , Regina M. A. Neves & Claudio Di
Vitta (2002) PHASE TRANSFER CATALYSIS IN SOLID–LIQUID SYSTEM AS A SELECTIVE METHOD
OF MONO-ALKYLATION OF α-SULFONYL THIOESTERS, Synthetic Communications, 32:10,
1483-1487, DOI: 10.1081/SCC-120004136
To link to this article: http://dx.doi.org/10.1081/SCC-120004136
Published online: 12 Dec 2006.
Submit your article to this journal
Article views: 17
View related articles
Citing articles: 1 View citing articles
Full Terms & Conditions of access and use can be found at
http://www.tandfonline.com/action/journalInformation?journalCode=lsyc20
Download by: [Gazi University]
Date: 14 January 2016, At: 00:13

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 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.
SYNTHETIC COMMUNICATIONS, 32(10), 1483–1487 (2002)
PHASE TRANSFER CATALYSIS IN
SOLID–LIQUID SYSTEM AS A SELECTIVE
METHOD OF MONO-ALKYLATION OF
a-SULFONYL THIOESTERS
*
Blanka Wladislaw, Liliana Marzorati,
Regina M. A. Neves, and Claudio Di Vitta
*
Instituto de Quımica, Universidade de Sao Paulo,
Av. Prof. Lineu Prestes, 748-C.P. 26077,
Sao Paulo, S.P., 05513-970, Brazil
ABSTRACT
a-Phenylsulfonyl methylthioacetate gave monoalkylated
products in high yields when treated with alkyl halides in
the presence of K2CO3 with TEBAC in CH2Cl2, at r.t. The
superiority of this method over that in the homogeneous
phase is discussed.
In the course of our investigations on the sulfenylation of a-sulfonyl
thioesters,1 the synthetic precursors of a-keto thioesters 1, we became
interested in a facile method of obtaining the starting material—a-alkyl
substituted a-sulfonyl thioacetates.
*Corresponding authors.
1483
Copyright & 2002 by Marcel Dekker, Inc.
www.dekker.com

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 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.
1484
WLADISLAW ET AL.
This communication reports the alkylation reactions of the a-phenyl-
sulfonyl thioacetate, showing the superiority of the phase transfer catalytic
method over the conventional homogeneous one.
When a-phenylsulfonyl methyl thioacetate 1 was submitted to reaction
with some alkyl halides, using NaH in DMSO as a base, the corresponding
monoalkylated products 2a–e were obtained, which, with exception of
benzyl bromide, were accompanied by the corresponding dialkyl derivatives,
3a–c, e (Scheme 1, Table 1).
Scheme 1.
These results differ from those reported for the alkylation of
a-sulfonylacetate,2,3 for which the monoalkylated derivatives were the
only reaction products, but are similar to those for the a-sulfonyl ketones,
which also let to mixtures of mono and dialkyl derivatives.4 This fact is in
accordance with the reduced resonance activation in the thiocarboxylate
moiety, which leads to a ketone-like carbonyl group.5
However, it was possible to obtain the monoalkylated derivatives as
the only reaction product when the alkylation was performed under the
phase transfer catalytic conditions.
Table 1. Alkylation Reactions of a-Phenylsulfonyl Methyl Thioacetate 1 by
Homogeneous Methoda
C6H5SO2CHRCOSMe 2
Yield %
C6H5SO2CR2COSMeb 3
Yield %
(GLC)
RX
(GLC)
(isol.)
CH3I
C2H5I
CH2¼CHCH2Br
C6H5CH2Br
p-Me-C6H4CH2Br
a
b
c
d
e
80
82
76
96
71
–
a
b
c
d
e
17
14
19
–
70
48
61
39
12
b
aNaH/DMSO; Identified by GC/MS.

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 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.
PHASE TRANSFER CATALYSIS IN SOLID–LIQUID SYSTEM
1485
Table 2. Alkylation Reactions of a-Phenylsulfonyl Methyl
Thioacetate 1 by Phase Transfer Catalytic Procedure in Solid–
Liquid Systema
C6H5SO2CHRCOSMe 2
Yield %b
RX
CH3I
C2H5I
C6H5CH2Br
p-Me-C6H4CH2Br
a
b
d
e
94
61
72
51
aK2CO3, TEBAC, CH2Cl2, r.t., 10 h (2a and 2b), 4 h (2d and 2e).
bIsolated yield.
Table 2 shows the yields of the monoalkylated products which were
obtained when a-phenylsulfonyl methyl thioacetate 1 was submitted to reac-
tion for 4 or 10 h with some alkyl halides using K2CO3 as a base, TEBAC as
a catalyst and dichloromethane as a solvent.
Proof was provided that these alkylations really occur by phase trans-
fer catalysis when the reaction of a-phenylsulfonyl methyl thioacetate 1 with
methyl iodide, in the absence of TEBAC, yielded the corresponding alkyl-
ated product 2a in 19% yield.
Therefore, it may be concluded that the phase transfer catalysis, in
the solid–liquid system, is a convenient method of the monoalkylation of
a-phenylsulfonyl thioacetate. Beside the high yields and the absence of
dialkylated products, some advantages should be added, such as the use
of K2CO3 instead of NaH or KOH, avoiding, respectively, a moisture sen-
sitive or hydrolizing base and using dichloromethane as a solvent instead of
DMSO, which is difficult to obtain in an anhydrous state.
EXPERIMENTAL
Alkylation of a-Phenylsulfonyl Methyl Thioacetate
Under Phase Transfer Conditions
Typical Procedure
To a mixture of thiolester (0.300 g, 1.30 mmol), K2CO3 (0.360 g,
2.60 mmol) and TEBAC (0.030 g, 0.130 mmol) were added 8.0 ml of
dichloromethane and methyl iodide (0.08 ml, 1.30 mmol). After stirring, at

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 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.
1486
WLADISLAW ET AL.
r.t. for 4 h, a second portion of catalyst (0.130 mmol) and methyl iodide
(1.30 mmol) was added, and the mixture was further stirred at r.t. for 6 h.
After this time the reaction mixture was poured into a satd. aqueous solu-
tion of ammonium chloride (20 ml), extracted with dichloromethane
(3 Â 20 ml), and dried over anhydrous magnesium sulfate. The crude oily
1
product (2a, 0.30 g, 94%) showed to be pure on GC analysis. H NMR
(d, CDCl3/TMS): 1.60 (d, 3H, J ¼ 7.1 Hz), 2.30 (s, 3H, SCH3), 4.18 (q,
1H, J ¼ 7.1 Hz), 7.53–7.88 (m, 5H). Calcd for C10H12O3S2: C%, 49.16;
H%, 4.95. Found: C%, 48.88; H% 4.86.
a-Ethyl-a-phenylsulfonyl methyl thioacetate (2b): Prepared as above.
The crude oily product was purified by column chromatography on silica
gel (hexane:benzene:ethyl acetate, 7:2:1 Yield 61%, v/v/v). m.p. 61.2–62.4ꢀC.
1H NMR (d, CDCl3/TMS): 0.98 (t, 3H, J ¼ 7.4 Hz), 1.92–2.12 (m, 2H), 2.32
(s, 3H, SCH3), 3.99 (dd, 1H, J ¼ 10.4 Hz, J0 ¼ 4.4 Hz), 7.51–7.87 (m, 5H).
Calcd for C11H14O3S2: C%, 51.14; H%, 5.46. Found: C%, 51.10; H%, 5.37.
For compound 2d, a second addition of catalyst and alkylating agent
was not necessary, and the reaction time was 4 h. For compound 2e, a
second addition of alkylating agent was not necessary. The crude products
were purified by recrystallization from the appropriate solvent.
a-Benzyl-a-phenylsulfonyl methyl thioacetate (2d): Yield: 72%, m.p.
81.4–82.7ꢀC (from hexane/chloroform). 1H NMR (d, CDCl3/TMS): 2.18
(s, 3H, SCH3), 3.26 (dd, 1H, J ¼ 13.4 Hz, J0 ¼ 11.4 Hz), 3.42 (dd, 1H,
J ¼ 13.4 Hz, J0 ¼ 3.6 Hz), 4.31 (dd, 1H, J ¼ 11.4 Hz, J0 ¼ 3.6 Hz), 7.08–7.22
(m, 5H) 7.55–7.92 (m, 5H). Calcd for C16H16O3S2: C%, 59.98; H%, 5.03.
Found: C%, 60.20; H%, 4.86.
a-( p-Methyl)benzyl-a-phenylsulfonyl methyl thioacetate (2e): Yield:
51%, m.p. 107.6–108.3ꢀC (from hexane/ethyl acetate). 1H NMR (d,
CDCl3/TMS): 2.18 (s, 3H, SCH3), 2.28 (s, 3H), 3.21 (dd, 1H, J ¼ 13.5 Hz,
J0 ¼ 11.2 Hz), 3.37 (dd, 1H, J ¼ 13.5 Hz, J0 ¼ 3.6 Hz), 4.29 (dd, 1H,
J ¼ 11.2 Hz, J0 ¼ 3.6 Hz), 6.97–7.05 (m, 4H), 7.57–7.91 (m, 5H). Calcd for
C17H18O3S2: C%, 61.05; H%, 5.42. Found: C%, 60.85; H%, 5.17.
Alkylation in Homogeneous Medium
Typical Procedure
A solution of a-phenylsulfonyl methyl thioacetate (1.00 g, 4.35 mmol)
in dry DMSO (6 ml) was added, via syringe, at r.t., to a suspension of NaH
(0.20 g, 4.35 mmol), previously washed with dry benzene, in DMSO (2 ml).
After stirring for 1 h at r.t., allyl bromide (0.38 ml, 4.35 mmol), dissolved in
DMSO (2 ml), was added dropwise via syringe. After stirring for 4 h at r.t.,

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 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.
PHASE TRANSFER CATALYSIS IN SOLID–LIQUID SYSTEM
1487
the reaction mixture was poured into satd. aqueous ammonium chloride,
(25 ml) and extracted with dichloromethane (3 Â 25 ml). The organic extract
was treated with water (2 Â 25 ml) and dried using anhydrous magnesium
sulfate. After removal of solvent, the crude solid product was purified by
recrystallization from hexane/ethyl acetate. 2c Yield 48%, m.p. 83.7–84.6ꢀC.
1H NMR (d, CDCl3/TMS): 2.30 (s, 3H, SCH3), 2.71–2.81 (m, 2H), 4.13 (dd,
1H, J ¼ 10.1 Hz, J0 ¼ 4.8 Hz), 5.07–5.17 (m, 2H), 5.54–5.74 (m, 1H),
7.53–7.88 (m, 5H). Calcd for C12H14O3S2: C%, 53.31; H%, 5.22. Found:
C%, 53.34; H%, 5.25.
Compounds 2a, 2b, 2d and 2e were prepared as described above.
ACKNOWLEDGMENTS
We are grateful to ‘‘Fundacao de Amparo a Pesquisa do Estado de
Sao Paulo’’ for financial support and ‘‘Conselho Nacional de
Desenvolvimento Cientıfico e Tecnologico’’ for the scholarships.
REFERENCES
1. Wladislaw, B.; Marzorati, L.; Donnici, C.L.; Biaggio, F.C.; Neves,
R.M.A.; Claro Junior, N.F. Phosphorus Sulfur and Silicon 1997,
23, 197.
2. Ashley, W.C.; Shriner, R.L. J. Am. Chem. Soc. 1932, 54, 4410.
3. Levkovskaya, C.G.; Gaseva, S.A.; Kryukova, T.C.; Mirshova, H.;
Voronkov, M.G. Zh. Org. Khim. 1984, 20, 1439.
4. House, H.O.; Larsor, J.K. J. Org. Chem. 1968, 33, 61.
5. Cronyn, M.W.; Chang, M.P.; Wall, R.A. J. Am. Chem. Soc. 1955, 77,
3031.
Received in the USA May 4, 2001

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 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.