An easy and practical synthesis of symmetrical thiosulfonic S-esters

Article abstract of DOI:10.1055/s-1998-1798

Symmetrical alkyl and aryl thiosulfonic S-esters were prepared in good to excellent yields by the acetyl chloride-activated zinc reduction of sulfonyl chlorides.

Full text of DOI:10.1055/s-1998-1798

894
LETTERS
SYNLETT
An Easy and Practical Synthesis of Symmetrical Thiosulfonic S-Esters
Fabrice Chemla
e
Laboratoire de Chimie des Organo-Eléments, URA 473 CNRS, Université Pierre et Marie Curie, 4, Place Jussieu, Tour 44-45, 2 étage, Boîte 183,
75252 Paris Cedex 05, France - FAX : (33) 01 44 27 75 67 - Email : fchemla@ccr.jussieu.fr
Received 15 June 1998
Abstract: Symmetrical alkyl and aryl thiosulfonic S-esters were
prepared in good to excellent yields by the acetyl chloride-activated zinc
reduction of sulfonyl chlorides.
then added as a mixture with acetyl chloride (1.1 equivalent) in ethyl
acetate (method B ). The desired thiosulfonic S-ester was always
13
contaminated with a small amount of the corresponding disulfone, but
this was easily removed by flash chromatography. However, from pipsyl
14
chloride 4h, the disulfone 6 was obtained in good yield instead of the
1
Thiosulfonic S-esters of the general formula 1 (Figure 1) are powerful
desired product.
2
sulfenylating reagents, more reactive than the commonly used
Our results are summarized in the Table 1. The products 5 were
disulfides 2, and more stable than the very reactive sulfenyl halides 3. In
identified by comparison of their NMR data and/or their physical
constants with those previously reported.
addition, they have found wide industrial applications as biologically
active compounds or in polymer production.
12-19
1
Concerning the mechanism of this transformation, the fact that the acyl
chloride is necessary for the reaction indicates an activation of the
sulfonyl halide. The mechanism we propose in Scheme 2 involves an
activation similar to the activation of sulfoxides by acyl chlorides in the
20
Pummerer reaction, leading to the corresponding oxosulfonium ion
Fig. 1
which reacts with zinc dust to give A. This species then leads to the
sulfinyl chloride 7 and a zinc(II) salt. The reduction of two molecules of
sulfinyl chloride by zinc dust has already been well-studied by
However, their use has been limited by the lack of easy and practical
preparations. The most often used procedures involve the oxidation of
thiols or disulfides, and then the use of chlorine, bromine or peroxides
(MCPBA, hydrogen peroxide or dinitrogen tetroxide) is often necessary.
Few methods are reported starting from sulfur compounds in higher
oxidation state, involving easily available starting materials. Among
these methods the reduction of sulfonyl halides with potassium iodide
or with copper/bronze, the reaction of potassium thiosulfonates and
diaryliodonium salts and the thermolysis of sulfonylhydrazines
21
Freeman and gives the observed symmetrical thiosulfonic ester,
1,3
through coupling (by an ionic or radical mechanism) and subsequent
rearrangement of the resulting disulfoxide.
4
5
6
7
8
deserve attention. We would like to report here an alternative method for
the easy preparation of both arene- and alkanethiosulfonic S-esters from
easily available sulfonyl chlorides.
9
In the course of our studies toward the formation of acylzinc species,
we were very surprised to observe that a mixture of benzenesulfonyl
chloride 4a and acetyl chloride react exothermically with zinc dust in
ethyl acetate at room temperature. To our surprise, the resulting product
did not incorporate the acyl choride moiety. As depicted in Scheme 1, a
mixture of benzenethiosulfonic S-phenylester (5a : R = Ph, 90%) and
10
benzene disulfone (6a : R = Ph, 10%) were obtained.
Scheme 2
In conclusion, we have disclosed here a new, practical and efficient
synthesis of symmetrical alkyl and aryl thiosulfonic S-esters. Further
studies in this field will be reported in due course.
Scheme 1
Thanks are due to F. Prian for his practical assistance and to Pr. J
Normant for many helpful discussions.
The reduction of sulfonyl chlorides by zinc dust in acidic water - ether
solvent has been reported to give a mixture of sulfinic acids, thiols and
11
disulfides. However, under our conditions, no reaction occurred in the
absence of the acyl halide. To obtain good yields of the thiosulfonate, it
was necessary to use exactly 1.5 equivalent of zinc dust; the reaction
medium had to be kept at room temperature by means of a cooling bath
References and Notes
(1) For a review, see : Zefirov, N.S.; Zyk, N.V.; Beloglazkina, E.K.;
Kutateladze, A.G.K. Sulfur Reports 1993, 14, 223.
12
(2) Trost, B.M. Chem. Rev. 1978, 78, 363; Palumbo, G.; Ferreri, C.;
D’Ambrosio, C.; Caputo, R. Phosph. & Sulfur 1984, 19, 235, and
references cited therein.
and 1.1 equivalent of acetyl chloride was added dropwise (method A ).
The reaction was also effective with other arenesulfonyl halides, like p-
tolylsulfonyl chloride 4b and 2,4,6-triisopropylsulfonyl chloride 4c. For
more reactive sulfonyl halides like p-methoxybenzenesulfonyl chloride
4d as well as for alkanesulfonyl halides (4e-g), this method gave a
reaction too exothermic to be easily controlled. The sulfonyl halide was
(3) For a recent example, see : Arterburn, J.B.; Perry, M.C.; Nelson,
S.L.; Dible, B.R.; Holguin, M.S. J. Am. Chem. Soc. 1997, 119,
9309.

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SYNLETT
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(4) For a preparation of methanethiosulfonic acid, methyl ester 4e
from DMSO, see : Lazlo, P.; Mathy, A. J. Org. Chem. 1984, 49,
2281; for a preparation of symmetrical thiosulfonic esters from
sulfinyl chlorides, see reference 13.
142.77, 136.50, 133.77, 131.48, 129.47, 128.86, 127.80, 127.45;
these data are identical to those previously reported : Billard, T.;
Langlois, B.R.; Large, S.; Anker, D.; Roidot, N.; Roure, P. J. Org.
Chem. 1996, 61, 7545.
(5) Palumbo, G.; Caputo, R. Synthesis 1981, 888.
(13) Method B : Preparation of methyl methanethiosulfonate 4e : to
zinc dust (49g, 0.75mol) in ethyl acetate (300mL) were added 1,2-
dibromoethane (1mL) and trimethyl-chlorosilane (2mL). The
mixture was heated to reflux, the zinc became brilliant and flakey.
After cooling, a mixture of methanesulfonyl chloride (57.25g,
0.5mol) and acetyl chloride (39.25g, 0.5mol) in 300mL ethyl
acetate was added dropwise at a rate such as the temperature did
not rise above 40°C. At the end of the addition, the zinc had totally
disappeared. After stirring two hours at room temperature, the
solution was washed with a 1M solution of hydrochloric acid in
water, then with brine and dried over magnesium sulfate. After
(6) Karrer, P.; Wehrli, W.; Biedermann, E.; dallaVedova, M. Helv.
Chim. Acta 1928, 11, 233.
(7) Xia, M.; Chen, Z. Synth. Commun. 1997, 27, 1309.
(8) Meier, H.; Menzel, I. Synthesis 1972, 267.
(9) Chemla, F.; Normant, J.F. Tetrahedron 1997, 53, 17265.
(10) Disulfones were identified (except for 6, see ref 14) by
comparison with described spectral data : Bartmann, E.A.
Synthesis 1993, 490.
(11) Klivenyi, F.; Vinkler, E.; Lazar, J. Acta Chim. Acad. Sci. Hung.
1965, 46, 357.
evaporation of the solvent, distillation at reduced pressure gave
1
methyl methanethiosulfonate 4e (18.9g, 60 %, bp = 90°C). H
0.5
(12) Method A : Preparation of phenyl benzenethiosulfonate 4a : to
zinc dust (1g, 16mmol) in ethyl acetate (60mL) were added 1,2-
dibromoethane (two drops) and trimethylchlorosilane (three
drops). The mixture was heated to reflux, the zinc became brilliant
and flakey. After cooling, benzenesulfonyl chloride (1.765g,
10mmol) was added in one portion, following by acetyl chloride
(0.79g, 10mmol) dropwise. The mixture became initially green,
and then turned to yellow. The reaction was followed by TLC.
After disappearance of the starting material, the solution was
washed with a 1M solution of hydrochloric acid in water, then
with brine and dried over magnesium sulfate. After evaporation of
the solvent, purification by flash chromatography over silica gel
13
NMR (CDCl , 400MHz) : δ 3.32 (s, 3H), 2.70 (s, 3H); ); C NMR
3
(CDCl , 100MHz): δ 20.70, 18.48; ; these data are identical to
3
those previously reported : : Lazlo, P.; Mathy, A. J. Org. Chem.
1984, 49, 2281.
1
(14) Spectral data for compound 6 : H NMR (CDCl , 200MHz) : δ 7.2
3
13
(d, 4H, J=7Hz), 7.6 (d, 4H, J=7Hz); C NMR (CDCl , 50MHz):
3
92.6, 129.2, 136.6, 138.1; MS (CI, NH ) : m/z 552, 520(100), 502,
3
470, 408, 394, 235, 125, 108; IR (KBr) : 1460, 1372, 1320, 1140,
-1
1000, 802, 725 cm ; mp = 112°C.
1
(15) Selected spectral data for compound 5b : H NMR (CDCl ,
3
400MHz) : δ 7.41 (d, 2H, J = 8Hz), 7.26 (d, 2H, J = 8Hz), 7.23 (d,
13
(eluent
:
cyclohexane
/
ethyl acetate 90:10) gave phenyl
2H, J = 8Hz), 7.16 (d, 2H, J = 8Hz), 2.42 (s, 3H), 2.38 (s, 3H);
C
1
benzenethiosulfonate 4a (1.13g, 90%).
400MHz) : δ 7.60-7.20 (m) C NMR (CDCl , 100MHz):
H NMR (CDCl ,
3
NMR (CDCl , 100MHz): δ 144.78, 142.17, 140.33, 136.49,
3
13
δ
3

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LETTERS
SYNLETT
1
130.30, 129.48, 125.58, 124.52, 21.61, 21,43; these data are
identical to those previously reported : Davis, F.A.; Reddy, R.E.;
Sczewczyk, J.M. J. Org. Chem. 1995, 60, 7037.
1
(18) Selected data for compound 5f : H NMR (CDCl , 400MHz) : δ
3
3.29 (td, 2H, J=6Hz, J’=1Hz), 3.12 (td, 2H, J=7Hz, J’=2Hz), 1.95
(m, 2H), 1.78 (m, 2H), 1.08 (t, 3H, J=7.5Hz), 1.04 (t, 3H,
J=7.3Hz); C NMR (CDCl , 100MHz): δ 64.65, 38.47, 23.54,
17.73, 13.50, 13.02; these data are identical to those previously
13
3
(16) Selected data for compound 5c : mp 105-106°C; H NMR
(CDCl , 400MHz) : δ 7.1 (s, 2H), 7.0 (s, 2H); 3.72 (hept, 2H,
3
reported : Smith, D.J.; Maggio, E.T.; Kenyon, G.L. Biochemistry
J=8Hz), 3.60 (hept, 2H, J=8Hz), 2.91 (m, 2H), 1.1-1.3 (m, 24H);
these data are consistent with those previously reported :
Adlington, R.M.; Barrett, A.G.M. J. Chem. Soc., Perkin Trans. I
1975, 14, 766.
1
(19) Selected spectral data for compound 5g : H NMR (CDCl ,
3
400MHz) : δ 3.51 (hept, 1H, J=8Hz), 3.25 (quint, 1H, J=8Hz),
1980, 1076.
13
1.3-1.5 (m, 12H); C NMR (CDCl , 100MHz): δ 55.55, 38.59,
1
3
(17) Selected data for compound 5d : H NMR (CDCl , 400MHz) : δ
3
24.46, 16.49. These data are consistent with those previously
reported : Derbesy, G.; Harpp, D.N. J. Org. Chem. 1995, 60, 1044.
7.52 (d, 2H, J = 9Hz), 7.29 (d, 2H, J = 9Hz), 6.89 (d, 2H, J =
9Hz), 6.86 (d, 2H, J = 9Hz), 3.88 (s, 3H), 3.85 (s, 3H); C NMR
13
(20) DeLucchi, O.; Miotti, U.; Modena, G. Org. React. 1991, 40, 157.
(CDCl , 100MHz): δ 163.65, 163.32, 138.46, 134.98, 129.99,
3
118.99, 115.03, 113.95, 55.83, 55.59; ; these data are identical to
those previously reported : Bell, K.H. J. Chem. Soc., Perkin Trans.
I 1988, 1957.
(21) Freeman, F.; Bartosik, L.G.; vanBui, N.; Keindl, M.C.; Nelson,
E.L. Phosph. & Sulfur 1988, 35, 375; Freeman, F. Chem. Rev.
1984, 84, 117; Freeman, F.; Keindl, M.C. Synthesis 1983, 913.