Synthesis of stable sulfines by oxidation of chlorodithioformates

Article abstract of DOI:10.1007/s00706-004-0165-y

The oxidation of chlorodithioformates with m-chloroperoxybenzoic acid in dichloromethane at room temperature provides an efficient stereoselective synthesis of (Z)-sulfines. The expected (Z)-configuration was confirmed by an X-ray structure determination.

Full text of DOI:10.1007/s00706-004-0165-y

Monatshefte f€ur Chemie 135, 879–884 (2004)
DOI 10.1007/s00706-004-0165-y
Synthesis of Stable Sulfines by Oxidation
of Chlorodithioformates
ꢀ
Ibrahim El-Sayed
Chemistry Department, Faculty of Science, El-Menoufeia University,
Shebin El-Kom, Egypt
Received November 24, 2003; accepted (revised) December 5, 2003
Published online April 9, 2004 # Springer-Verlag 2004
Summary. The oxidation of chlorodithioformates with m-chloroperoxybenzoic acid in dichloro-
methane at room temperature provides an efficient stereoselective synthesis of (Z)-sulfines. The
expected (Z)-configuration was confirmed by an X-ray structure determination. The sulfines are
reactive dienophiles and react with 2,3-dimethyl-1,3-butadiene to give the corresponding dihydrothio-
pyran-S-oxide.
Keywords. Sulfines; Chlorodithioformates; Oxidation; 1,3-Dienes; Dihydrothiopyran-S-oxides.
Introduction
Sulfines (thiocarbonyl-S-oxides) 1 constitute an interesting class of tetracoordinate
sulfur containing cumulative double bonds. Their chemistry has developed rapidly
during the past twenty years [1–9]. Sulfines undergo a multitude of interesting and
synthetically useful reactions such as cycloadditions, rearrangements, and nucleo-
philic additions at carbon or sulfur atoms [9, 10]. In this context, chlorodithiofor-
mates 4 represent a special class of thiocarbonyl compounds and we have over the
years developed a specific interest in these type of sulfur containing molecules
[11–13]. The corresponding sulfines of 4 have been rather neglected and rarely
appeared in literature despite their interesting non-linear heterocumulene structure
and various practical applications. These compounds bear a leaving group at the
sulfine carbon atom and are expected to be prone to nucleophilic displacement
reactions with various reagents, with either retention or inversion of configuration
at the sulfine moiety [14]. On the basis of this observation nucleophilic displace-
ment reactions with sulfine carrying a good leaving group at the sulfine carbon
atom would provide a potential method for the preparation of a variety of sulfines
from substrates that already contain the sulfine unit. With the aim of further
ꢀ
B-2610, Antwerp, Belgium. E-mail: ibrahim@uia.ua.ac.be
Present address: University of Antwerp, Faculty of Pharmacy, Department of Medicinal Chemistry,

880
I. El-Sayed
developing chlorodithioformates 4 as tools for organic synthesis, we became inter-
ested in the oxidation of 4 by m-chloroperoxybenzoic acid (m-CPBA). Another
intriguing point to be addressed is the relative dienophilicity of the >C¼S double
bonds of 4 and the corresponding sulfines 5 toward [4 þ 2] cycloaddition reactions.
The present work also quantifies the steric demands of the R1S group of 4 and the
competition for the diastereomerization in the resulting sulfines. In addition, we
examined the intramolecular selective oxidation of the starting chlorodithiofor-
mates 4, which contain two oxidizable sulfur atoms and extra functional groups
such as e.g. the C¼C double bond in chlorodithioformate 4c.
Results and Discussion
The starting chlorodithioformates 4a–4c were prepared from the corresponding
thiophenol 2 and thiophosgene 3 in chloroform in the presence of NaOH [15].
Oxidation of chlorodithioformates 4a–4c with one equivalent of m-CPBA was
achieved in dichloromethane at 0ꢁC. The orange color of 4 changed to light
yellow after 15 minutes and 4 quantitatively afforded the corresponding sulfines
5 (Scheme 1). To our delight, NMR spectra of the crude materials showed that
the oxidation of the thiocarbonyl group was stereoselective and predominantly a
single isomer was formed. No evidence for the oxidation of the other sulfur atom
of 4 or the C¼C double bond of 4c was detected. It should be noted that the
sulfines 5 are stable under aqueous conditions and this is in sharp contrast to
other reported sulfines containing strong electron withdrawing substituents (e.g.
SO2R and Cl), which readily hydrolyse into the corresponding methylene com-
pounds [16]. Consequently sulfines containing strong electron withdrawing
substituents can not be prepared using the procedure described above, which
Scheme 1

Synthesis of Stable Sulfines
881
Fig. 1. The molecular structure of sulfine 5a with 50% probability ellipsoids
involves an aqueous work up. Sulfines 5 can also be kept without deterioration
for months at ambient temperature, and can be purified by column chromatogra-
phy on silica gel or by recrystallization.
The crude sulfines 5 were analyzed by NMR. The quaternary (>C¼S¼O)
carbon of the sulfines 5 resonates at 171.22 ppm for 5a, 171.27 ppm for 5b, and
173.69 ppm for 5c in 13C NMR, upfield from the corresponding (>C¼S) group of
the starting chlorodithioformates 4 (189.60 ppm for 4a, 191.80 ppm for 4b, and
193.72 ppm for 4c). Furthermore, the strong IR absorptions at 1155 and 1035 cmꢂ1
for 5a, at 1150 and 1033 cmꢂ1 for 5b, and at 1145 and 1023 cmꢂ1 for 5c can be
attributed to the (>C¼S¼O) group. Both 13C NMR and IR spectra compared well
with that reported for other sulfines [9].
An X-ray crystallographic analysis (Fig. 1) unambiguously confirmed the (Z)-
geometry and the non-linearity of the >C¼S¼O system of 5a. The length of the
˚
>C¼S and S¼O bonds were found to be 1.63 and 1.46 A, while the >C¼S¼O angle
was found to be 114.14ꢁ. The sulfine exhibits a non-planar arrangement with the
oxygen atom located trans to the pentachlorophenylthio group. The dihedral angle
between the planes of the sulfine group and the pentachlorophenylthio group is
99.42ꢁ, demonstrating a non-planar arrangement around the C(15)–S(3) bond. The
sulfine moiety ꢀ-plane and the pentachlorophenylthio group are arranged perpendic-
ular to each other, where the bulky pentachlorophenylthio group hinders the sulfine
moiety to adopt a position in the same plane as the pentachlorophenythio moiety.
The (Z)-stereochemistry of the oxidation product is noteworthy. It is thermo-
dynamically preferred and this preference has seldom been reported. In order to
rationalize the observed selectivities we performed B3LYP=6-31G(d) calculations
with the Jaguar program [17]. The results agreed well with the experiments. The
energy difference between the (Z)- and (E)-isomers of 5a is 3.3 kJ=mol at the
B3LYP=6-31G(d) level favoring the (Z)-isomer. Absence of (Z)=(E)-isomerization

882
I. El-Sayed
Scheme 2
of 5a was observed when subjected to thermolysis in toluene at 110ꢁC. Interest-
ingly, and to the best of our knowledge, this is the first confirmation of the con-
figuration of a sulfine derived from 4.
Despite the presence of a chlorine atom at the sulfine carbon atom, 5a was
sluggish in the reaction with 1,3-butadiene derivatives. This is probably due to the
retarding effect exerted by the bulky pentachlorophenyl group. The hetero-Diels-
Alder reaction between 5a and 2,3-dimethyl-1,3-butadiene was carried out at room
temperature in chloroform for 3 days, forming dihydrothiopyran-S-oxides 6 in only
50% yield (Scheme 2). Fortunately, by performing the reaction at 70ꢁC the
cycloaddition was completed in 4 h (96% isolated yield). The NMR and TLC
analysis showed that a single diastereomer had been obtained. This implies that
during the cycloaddition the initial stereochemistry present in the sulfine (Z) is
retained in the adduct (i.e. the chlorine atom and sulfoxide oxygen are cis to each
other).
It should be noted that while the hetero-Diels-Alder reactions of 5 with 1,3-
diene derivatives gave the corresponding dihydrothiopyran-S-oxides, the reaction
with 4 leads to the labile 2H-3,6-dihydrothiopyrans, which spontaneously eliminate
hydrogen chloride to form the 2H-thiopyrans [13]. It may be suggested that the
variable chemical behavior of 4 and their S-oxides 5 in [4 þ 2] cycloaddition
reactions is due to disruption of the aromatic character in the 2H-3,6-dihydrothio-
pyran product.
It may be concluded from the results described in this paper that the thiocar-
bonyl group in chlorodithioformates 4 is oxidised selectively, and neither sulfur nor
the C¼C double bonds reacted. The study also revealed the different reactivity of 4
and 5 as dienophiles in [4 þ 2] cycloaddition reactions. The cycloaddition of sul-
fines with dienes proceeds stereospecifically to yield dihydrothiopyran-S-oxides,
therefore these sulfines are interesting substrates in asymmetric cycloaddition reac-
tions and the results presented here clearly stimulate further research of asym-
metric reactions with sulfines.
Experimental
All 1H and 13C NMR experiments (CDCl3) were carried out with a Varian Unity 400 MHz spectrom-
1
eter (400MHz for H, 100 MHz for 13C). Chemical shifts are reported in ppm relative to TMS using
appropriate solvent signals as internal standard. Mass spectra analyses were performed with Kratos
€
50tc spectrometer, and melting points were recorded on a Buchi melting point apparatus. TLC was

Synthesis of Stable Sulfines
883
done on Merck Kieselgel F254 precoated plates (Merck), the microanalysis was performed in the
microanalysis lab. at Cairo University; these results agreed favourably with the calculated values.
Single crystals suitable for X-ray studies from sulfine 5a were grown in a mixture of CH2Cl2 and
n-hexane (1=3), intensity data were measured at room temperature on an Enraf-Nonius CAD4 dif-
˚
fractometer with graphite-monochromated Mo Kꢁ radiation, wavelength: 0.71073A, cell measure-
ment temperature: 298 K, crystal color: light yellow, crystal shape: prismatic, crystal system: triclinic,
ꢁ
˚
˚
˚
unit cell parameters: a ¼ 6.1559 (3) A, b ¼ 7.6979 (4) A, c ¼ 13.7443 (7) A, ꢁ ¼ 100.678 (3) , ꢂ ¼
3
ꢁ
ꢁ
˚
98.165 (3) , ꢃ ¼ 102.730 (3) , space group P-1, cell volume: 612.84 (5) A , Rall: 0.029, cell formula
units Z: 2, absorption coefficient: 0.65 mmꢂ1, F(000): 266. X-ray data were deposited at the Cambridge
Crystallographic Data Center under No. CCDC 224948, copies of the data can be obtained free of
charge on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [Fax: int. code þ44-1223-
336033, E-mail: deposit@ccdc.cam.ac.uk]. Chlorodithioformates 4 were prepared according to lit-
erature procedures [15].
Chloro(pentachlorophenylthio) sulfine (5a, C7Cl6OS2)
To a stirred solution of 300 mg of 4a (0.83 mmol) in 10cm3 of CH2Cl2 at 0ꢁC, 179 mg of m-chloro-
peroxybenzoic acid (1.04 mmol, 80%) dissolved in 5 cm3 of CH2Cl2 were added within 10min. After
15min the orange color changed to light yellow, the solution was washed successively with saturated
aqueous NaHCO3 (3ꢃ10 cm3) and saturated brine (30 cm3). The organic layer was dried (MgSO4),
filtered, and concentrated under reduced pressure to leave 5a as a single isomer. Recrystallisation from
CH2Cl2=n-hexane (1=3) furnished pale yellow crystals (288mg, 92%), mp 140–143ꢁC; IR (KBr):
ꢄꢀ¼ 1155, 1035 (ꢄC¼S¼O) cmꢂ1
;
13C NMR (CDCl3): ꢅ ¼ 126.85, 133.15, 137.52, 139.10, 171.22
(>C¼S¼O) ppm; MS: m=z (%) ¼ 374 (7, Mþ).
Chloro(2,4,5-trichlorophenylthio) sulfine (5b, C7H2Cl4OS2)
The procedure as given for 5a was followed starting from 200 mg of 4b (0.68 mmol) and 147 mg of m-
CPBA (0.85 mmol, 80%). The sulfine was purified by crystallization from CH2Cl2=n-hexane (1=3) to
give pale yellow crystals (190mg, 90%), mp 99–102ꢁC; IR (KBr): ꢄꢀ¼ 1150, 1033cmꢂ1 (ꢄC¼S¼O), 1H
NMR (CDCl3): ꢅ ¼ 7.47 (s, 1H), 7.57 (s, 1H) ppm; 13C NMR (CDCl3): ꢅ ¼ 129.18, 131.53, 131.62,
132.39, 134.03, 137.47, 171.27 (>C¼S¼O) ppm; MS: m=z (%) ¼ 306 (16, Mþ).
Chloro(1,2,2-triphenylethenylthio) sulfine (5c, C21H15ClOS2)
The procedure given for 5a was followed with 300 mg of 4c (0.82 mmol) and 147 mg of m-CPBA
(0.85 mmol, 80%). After usual work-up, the corresponding sulfine was formed as a yellow solid.
Further crystallization from CH2Cl2=n-hexane (1=3) afford analytically pure yellow crystals of 5c.
1
Yield 279 mg (89%), mp 177–179ꢁC; IR (KBr): ꢄꢀ¼ 1145, 1023 cmꢂ1 (ꢄC¼S¼O); H NMR (CDCl3):
ꢅ ¼ 6.95–7.45 (m, 15H) ppm; 13C NMR (CDCl3): ꢅ ¼ 127.60, 127.83, 128.16, 128.36, 128.52, 129.99,
130.36, 130.74, 136.52, 140.06, 141.51, 149.92, 173.78 (>C¼S¼O) ppm; MS: m=z (%) ¼ 382 (28,
Mþ).
3,6-Dihydro-4,5-dimethyl-2-(chloro)-2-(pentachlorophenylthio)-2H-thiopyran-S-oxide
(6, C13H10Cl6OS2)
To a solution of 200 mg of 5a (0.66 mmol) in 5 cm3 of CHCl3 was added an excess of 2,3-dimethyl-1,3-
butadiene (3 cm3). After stirring for 4 h at 80ꢁC the volatiles were evaporated in vacuo and crude 6 was
crystallized from CH2Cl2=n-hexane (1=3) giving analytically pure 6 as colorless crystals (293mg,

884
I. El-Sayed: Synthesis of Stable Sulfines
96%); mp 168–170ꢁC; IR (KBr): ꢄꢀ¼ 1073 (ꢄS¼O) cmꢂ1; 1H NMR (CDCl3): ꢅ ¼ 1.75 (s, 3H), 1.77 (s,
3H), 2.84 and 3:54 (ABq, J ¼ 17.60 Hz, 2H), 3.37 and 4.06 (ABq, J ¼ 17.18Hz, 2H) ppm; 13C NMR
(CDCl3): ꢅ ¼ 19.15, 20.11, 40.92, 52.85, 89.24, 118.10, 124.98, 129.67, 132.51, 137.10, 141.44, MS:
m=z (%) ¼ 456 (4, Mþ).
Acknowledgments
The author thanks Dr. H. Ottosson, Uppsala University, Sweden for performing the computation for 5a.
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