New contributions to the chemistry of 2-chloro-2-(chlorothio)propanedioic diesters and diamides

Article abstract of DOI:10.1002/1099-0690(200207)2002:13<2039::AID-EJOC2039>3.0.CO;2-X

The pyridine-catalyzed reaction between a number of propanedioic acid derivatives 1 and thionyl chloride has been investigated in detail. Contrary to popular belief the straight-forward formation of the corresponding α-chloro sulfenyl chlorides 2 is the exception rather than the rule. The propanediamide 2e, not available by the "standard" reaction of 1e with thionyl chloride, is surprisingly formed by reaction of 1e with sulfur dichloride. The usefulness of 2 as thiosulfine 4 precursors has been demonstrated. Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002.

Full text of DOI:10.1002/1099-0690(200207)2002:13<2039::AID-EJOC2039>3.0.CO;2-X

FULL PAPER
New Contributions to the Chemistry of 2-Chloro-2-(chlorothio)propanedioic
Diesters and Diamides
Mohamed A. M. Hawata,[a] Abdel M. El-Torgoman,[a] Salah M. El-Kousy,[b]
Abd El-Hamid Ismail,[b] Jørgen Øgaard Madsen,[c] Inger Søtofte,[d] and
Alexander Senning*[e]
Keywords: Sulfenyl chlorides / Sulfur heterocycles / Amides / Thiosulfines / Dithiiranes
The pyridine-catalyzed reaction between a number of pro-
panedioic acid derivatives 1 and thionyl chloride has been
investigated in detail. Contrary to popular belief the straight-
forward formation of the corresponding α-chloro sulfenyl
chlorides 2 is the exception rather than the rule. The pro-
panediamide 2e, not available by the ‘‘standard’’ reaction of
1e with thionyl chloride, is surprisingly formed by reaction of
1e with sulfur dichloride. The usefulness of 2 as thiosulfine 4
precursors has been demonstrated.
( Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany,
2002)
Our renewed interest in active methylene compound 1 the corresponding acyldithio compounds 5, which sub-
derived α-chloroalkanesulfenyl chlorides 2,[1Ϫ6] [see Equa- sequently can be ‘‘unzipped’’ with morpholine[3,7] to form
tion (1)] stems from the following considerations:
3/4, or chlorinated with formation of the corresponding
1) Compounds 2 are in principle convenient intermediates chlorodithio compounds 6, which in turn upon dechlorina-
for the generation of transient dithiiranes/thiosulfines 3/ tion under the proper conditions might generate 3/4
4,[3,7] i.e. via their conversion with thiocarboxylic acids to [Scheme 1 and Equation (2)].
(1)
Scheme 1
[a]
Department of Applied Chemistry, Technical University of
Denmark,
2800 Kgs. Lyngby, Denmark
[b]
Department of Chemistry, Faculty of Science, Menoufia
University,
Shebin El-Kom, Egypt
(2)
E-mail: science@shebin.eun.eg
[c]
Department of Chemistry, Technical University of Denmark,
2800 Kgs. Lyngby, Denmark
E-mail: jom@kemi.dtu.dk
[d]
Department of Chemistry, Technical University of Denmark,
Thiosulfines 4 typically suffer disproportionation accord-
ing to Equation (3): and in subsequent cycloadditions yield
1,2,4-trithiolanes 9 and/or 1,2,4,5-tetrathianes 10 [Equa-
tion (4) and (5)].
2800 Kgs. Lyngby, Denmark
E-mail: is@kemi.dtu.dk
[e]
Department of Chemistry, Technical University of Denmark,
2800 Kgs. Lyngby, Denmark
E-mail: aes@kemi.dtu.dk
Eur. J. Org. Chem. 2002, 2039Ϫ2045  WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002 1434Ϫ193X/02/0713Ϫ2039 $ 20.00ϩ.50/0
2039

A. Senning et al.
FULL PAPER
Results and Discussion
The standard procedure for the preparation of 2 from 1
is treatment of the latter with thionyl chloride in the pres-
ence of a catalytic amount of pyridine [Equation (1) and
Table 1].[1]
(3)
The preparation of 2a differs significantly from that of
the known 2b[1] in that 2a can be purified by column chro-
matography (yield 58%), which also yields the correspond-
ing disulfide 11a (yield 25%) and trisulfide 12a (yield 10%)
[Equation (6)].
(4)
(5)
(6)
2) Dechlorination of 2 would, in principle, generate the
highly reactive thiones 7,[8] which are useful for cycloaddi-
tions etc. (Scheme 2).
It seems safe to assume that the impurities in crude 2b
are therefore 11b and 12b.
We were unable to prepare bis(2,2,2-trichloroethyl)-2-
chloro-2-(chlorothio)propanedioate (2c) and the corres-
ponding 2,2,2-tribromoethyl compound 2d: the diester 1c,
seemingly highly analogous with other compounds 1, only
yielded the corresponding disulfide 11c (a remarkable Cl14
compound) while 1d failed to react with thionyl chloride
[Equation (7)].
(7)
Scheme 2
3) The persistent failure of closely related α-chloro-
alkanesulfenyl chlorides to form the corresponding disulf-
ides 11 upon reduction[4,5] (otherwise a standard reaction
of sulfenyl chlorides[9]) suggested a need for a better under-
standing of the substitution/reduction pattern of α-chloro-
alkanesulfenyl chlorides including 2.
The propanediamide 1e gave the disulfide 11e when
treated with thionyl chloride [Equation (8)].
(8)
Table 1. Reactions of propanedioic acid derivatives 1 with SOCl2
Starting material
Product(s) (yield, %)
Comments
1a
1b
2a (58), 11a (25),
12a (10)
after column chromatography, analytically pure
2b (99)
crude product, satisfactory for synthetic purposes; decomposes upon attempted
column chromatography; can be distilled[1]
analytically pure
1c
1d
1e
11c (71)
1d
11e (66)
no reaction
analytically pure; 2e can be prepared from 1e and SCl2 in boiling benzene
2040
Eur. J. Org. Chem. 2002, 2039Ϫ2045

2-Chloro-2-(chlorothio)propanedioic Diesters and Diamides
FULL PAPER
However, 2e could be obtained in an unorthodox fashion
from 1e and sulfur dichloride in boiling benzene.
When we treated 2a,b with thioacetic acid, thiobenzoic
acid, or thiophenol all substitutions proceeded in the ex-
pected uneventful fashion, yielding 5aa, 5ab, 5ac, 5bb, and
5bc, respectively. An unorthodox result was the formation
of 1e from 2e and thioacetic acid [Equation (9)].
(9)
Figure 1. The molecular structure of 11a with 50% probability
ellipsoids
The substitution/reduction reactions of 2 with various
nucleophiles were also difficult to predict. Thus, treatment
of 2a with p-toluenesulfinate led to three products: the
simple substitution product 12a, the disulfide 11a, and the
1,2,4-trithiolane 9a [Equation (10)], whereas the corres-
ponding reaction of 2e gave disulfide 11e and 1,2,4-trithiol-
ane 9e [Equation (11)].
Table 2. Crystal data for compound 11a
11a
Formula
Mol. wt.
C10H12Cl2O8S2
395.24
M.p. (°C)
Cryst. system
Space group
72.5Ϫ73.5
monoclinic
P21/c
10.98520(10)
18.0271(2)
8.26470(10)
Ϫ
90.94
Ϫ
1636.45(3)
4
˚
a (A)
˚
b (A)
˚
c (A)
α (°)
β (°)
γ (°)
(10)
3
˚
V (A )
Z
Total number
of unique refl.
[I Ͼ 2σ(I)]
θ range (°)
R (obs. data)
wR2 (all data)
4078
3469
1.85Ϫ29.49
0.0344
0.0933
(11)
While the formation of 11a from 2a may or may not in-
volve the thione 7a as intermediate (Scheme 2), it is not
very likely that the 1,2,4-trithiolane 9a can be formed in
any other way than by cycloaddition of the thione 7a and
the thiosulfine 4a [Equation (4)]. Although a spontaneous
disproportionation of the S1 compound 7a to the S2 com-
pound 4a and, presumably, an unspecified sulfur-free spe-
cies is not exactly trivial, reactions of this kind do have
precedent in the literature, especially in the presence of ox-
idants.[10] While a number of reducing agents convert 2 effi-
ciently to 11, the corresponding electrochemical reduction
yields 11 in analytical purity without chromatographic
workup.
Although the reaction of 2 with aqueous trithiocarbonate
leading to the 1,2,4,5-tetrathiane 10 could be formulated as
a straightforward reduction it is tempting to consider the
intermediate formation of 3/4 via a labile 1,2,4-trithiolane-
3-thione precursor 13 [Equation (12)].
(12)
The solid-state structure of the key compound 11a was
Chlorination of the disulfides 11 leads, as expected, to
determined by X-ray crystallography (Figure 1, Table 2). the corresponding compounds 2. However, in the case of
The structure appears to be devoid of strain and largely 11e the α-chloro sulfenyl chloride thus formed is accompan-
determined by the electrostatic repulsions of the chlorine ied by the dichloromethylene compound 14e [Equa-
atoms and the geminal carbonyl groups.
tion (13)].
Eur. J. Org. Chem. 2002, 2039Ϫ2045
2041

A. Senning et al.
FULL PAPER
Experimental Section
All commercial chemicals and solvents were used as received except
sulfur dichloride which was distilled immediately prior to use.
Bis(2,2,2-trichloroethyl) propanedioate (1c),[12] bis(2,2,2-tribromoe-
thyl) propanedioate (1d),[13] N,N-di-tert-butylpropanediamide
(1e),[14] and diethyl 2-chloro-2-(chlorothio)propanedioate (2b)[1]
were prepared according to literature procedures. The electrochem-
ical reductions were performed in a three-compartment H cell at
constant potential by means of a home-built potentiostat.[13] The
stationary phase for column chromatography was Merck silica gel
60, particle size 0.040Ϫ0.063 mm. The eluent for TLC was hexane/
ether (1:1), and the eluent for column chromatography petroleum
ether (b.p. 40Ϫ60 C)/diethyl ether (10:1). The NMR spectra were
recorded in CDCl3 solution with a Bruker AC 250 or Bruker AM
500 apparatus. IR spectra were recorded on a PerkinϪElmer FTIR
1700 with KBr wafers, those of liquids neat between NaCl win-
dows. The mass spectra were obtained with a VG (Mass Lab) Trio-
2 quadrupole instrument. Chemical ionization spectra were re-
corded with NH3 as reagent gas. The elemental analyses were car-
ried out by the Microanalytical Laboratory of the Department of
Physical Chemistry, University of Vienna, A-1090 Vienna, Austria.
(13)
The chlorination of the 1,2,4-trithiolane 9a yields, as ex-
pected, 2a and the corresponding gem-disulfenyl dichloride
15a while the analogous treatment of 9e leads to 2e and 14e.
The chlorination of 5aa was followed in small-scale qual-
itative experiments: it is relatively fast with chlorine and
relatively slow (and requiring heating) with sulfuryl chlor-
ide. In both cases (as judged by MS) varying amounts of
thiosulfenyl chloride 6a and gem-disulfenyl dichloride 15a
(cf. Scheme 1) were obtained, along with disulfide 11a, tris-
ulfide 12a, and tetrasulfide 16a, i.e. tetramethyl 1,6-
dichloro-2,3,4,5-tetrathiahexane-1,1,6,6-tetracarboxylate.
Because of the very similar polarities of the components of
these mixtures small-scale column chromatography could
not effect complete separations. We chose not to pursue this
matter any further even though the formation of the sulfur-
rich compounds 12a and 16a is puzzling.
Reaction of Dimethyl Propanedioate (1a) with SOCl2: Dimethyl pro-
panedioate 1a (1.50 mL, 13 mmol), thionyl chloride (12.4 mL,
170 mmol), and pyridine (0.20 mL, 2.6 mmol) were refluxed for
7.5 h. The reaction mixture was allowed to cool, then filtered, and
the solvents evaporated in vacuo. Yield 2.76 g of crude product
which was column chromatographed. The following products (in
order of elution) were obtained: 2a (1.74 g, 58%), 11a (0.64 g, 25%),
12a (0.28 g, 10%).
Upon heating with elemental sulfur compounds 2 all be-
have differently: 2a gives the disulfide 11a and the trisulfide
12a as well as the 1,2,4-trithiolane 9a; compound 2b is
cleanly oxidized to the disulfide 11b; and 2e forms 11e as
well as the 1,2,4-trithiolane 9e and the dichloromethylene
compound 14e [Equation (14)].
Dimethyl 2-Chloro-2-(chlorothio)propanedioate (2a): Yellow oil, b.p.
87Ϫ91 °C/0.5 Torr. IR: ν˜ ϭ 2957 (aliph. CH), 1748 (CϭO), 1435,
1354, 1250, 1109, 1007, 947, 905, 846, 763, 624, 523 cmϪ1 1H
.
NMR: δ ϭ 3.95 (s) ppm. 13C NMR: δ ϭ 54.8 (2 CH3), C-2 signal
not observed, 164.2 (2 CϭO) ppm. MS (EI): m/z (%) ϭ 232 (12)
[M], 197 (0.6) [C5H6ClO4S], 173 (15) [C3H3Cl2O2S], 162 (10)
[C5H6O2S], 153 (18), 138 (23) [C3H3ClO2S], 109 (25), 103 (25)
[C3H3O2S], 79 (32), 59 (100) [C2H3O2], 45 (10). C5H6Cl2O4S
(233.07): calcd. C 25.77, H 2.60; found C 25.91, H 2.56.
(14)
In particular, the formation of 14e in the absence of an
external source of chlorine is baffling.
When the unsymmetrical disulfide 5ab was subjected to
our standard ‘‘unzipping’’ reaction with morpholine[11,3,7]
we obtained the 1,2,4-trithiolane 9a, the 1,2,4,5-tetrathiane
10a, and, contrary to expectation, the disulfide 11a [Equa-
tion (15)].
Tetramethyl 1,4-Dichloro-2,3-dithiabutane-1,1,4,4-tetracarboxylate
(11a): Colorless crystals, m.p. 72.5Ϫ73.5 °C. IR: ν˜ ϭ 2957 (aliph.
CH), 2848 (aliph. CH), 1742 (CϭO), 1435, 1248, 1435, 1248, 1109,
1007, 947, 905, 846, 763, 706, 635 cmϪ1 1H NMR: δ ϭ 3.85 (s)
.
ppm. 13C NMR: δ ϭ 54.8 (4 CH3), C-1, C-4 signals not observed,
164.2 (4 CϭO) ppm. MS (EI): m/z (%) ϭ 394 (14) [M], 335 (4)
[C8H9Cl2O6S2], 330 (2) [C10H12Cl2O8], 229 (12), 194 (4)
[C5H6O4S2], 180 (8) [C4H4O4S2], 162 (12), 153 (22), 137 (42), 109
(30), 103 (27), 95 (25), 79 (18), 59 (100) [C2H3O2], 45 (8).
C10H12Cl2O8S2 (395.24): calcd. C 30.39, H 3.06, S 16.23; found C
30.38, H 3.04, S 18.15. In light of the overwhelming structural
proof for 11a, including X-ray data, we consider the low sulfur
analysis unimportant. An X-ray single crystal structure determina-
tion was performed (cf. Figure 1, Table 2).
(15)
Tetramethyl
1,5-Dichloro-2,3,4-trithiapentane-1,1,5,5-tetracarb-
oxylate (12a): Colorless crystals, m.p. 79.5Ϫ80.5 °C. IR: ν˜ ϭ 2961
(aliph. CH), 1738 (CϭO), 1436, 1252, 1018, 948, 843, 763, 706, 635
The observation of the two first compounds clearly indic-
ates the intermediacy of the corresponding thiosulfine 4a.
The corresponding ‘‘unzipping’’ of 5aa with morpholine
was unrewarding. An inconveniently large number of ill-
defined products was formed, none of which was the ex-
pected 9a,10a, and/or 11a.
1
cmϪ1. H NMR: δ ϭ 3.85 (s) ppm. 13C NMR: δ ϭ 54.6 (4 CH3),
C-1, C-5 signals not observed, 163.9 (4 CϭO) ppm. MS (EI): m/z
(%)
ϭ 426 (3) [M], 394 (22) [C10H12Cl2O8S2], 335 (9)
[C8H9Cl2O6S2], 330 (6) [C10H12Cl2O8], 261 (8), 229 (81)
[C5H6ClO4S2], 197 (10) [C5H6ClO4S], 180 (9) [C4H4O4S2], 162 (12)
[C5H6O4S], 153 (23), 137 (43), 109 (23), 103 (19), 79 (16), 59 (100)
2042
Eur. J. Org. Chem. 2002, 2039Ϫ2045

2-Chloro-2-(chlorothio)propanedioic Diesters and Diamides
FULL PAPER
[C2H3O2]. C10H12Cl2O8S3 (427.30): calcd. C 28.11, H 2.83; found
C 27.84, H 2.60%.
Reactions Between 2 and Mercapto Compounds. General Proced-
ure:[11] Equimolar amounts (10 mmol each) of 2 and the mercapto
compound (thioacetic acid, series a, thiobenzoic acid, series b, or
thiophenol, series c) were dissolved in tetrachloromethane and
heated at 50Ϫ60 °C until TLC showed that the reaction was com-
plete (3 h). In the case of 5aa rapid reaction took place at room
temperature and was complete after 1 h. After evaporation of the
solvent 6aa (2.72 g, 100%) was obtained by recrystallization from
diethyl ether while 5ab (2.45 g, 73%), 5ac (2.30 g, 75%), 5bb (2.80 g,
77%), and 5bc (2.50 g, 75%) were obtained after column chromato-
graphy.
Reaction of Bis(2,2,2-trichloroethyl) Propanedioate (1c) with SOCl2:
Bis(2,2,2-trichloroethyl) propanedioate[12] (47.3 g, 130 mmol),
thionyl chloride (124 mL, 1.70 mol), and pyridine (0.20 mL,
2.6 mmol) were stirred at room temperature until TLC showed that
the reaction was complete (10 h). The reaction mixture was allowed
to cool, filtered, and the solvents evaporated in vacuo. It was then
cooled and triturated with diethyl ether/petroleum ether (1:1). Yield
40.5 g (73%) crude product, m.p. 109Ϫ114 °C, which was recrystal-
lized from diethyl ether/petroleum ether (1:2) to give colorless crys-
tals (39.4 g, 71%) of tetrakis(2,2,2-trichloroethyl) 1,4-dichloro-2,3-
dithiabutane-1,1,4,4-tetracarboxylate (11c), m.p. 116.5Ϫ117.5 °C.
Dimethyl 2-(Acetyldithio)-2-chloropropanedioate (5aa): Colorless
crystals, m.p. 67.0Ϫ68.0 °C. IR: ν˜ ϭ 2961 (CH), 1760 (OCϭO),
1733 (SCϭO), 1436, 1350, 1270, 1228, 1113, 1023, 948, 849, 763,
IR: ν˜ ϭ 2980 (aliph. CH), 1753 (CϭO), 1188, 763, 718, 575 cmϪ1
.
660 cmϪ1 1H NMR: δ ϭ 2.43 (s, 3 H, CH3CO), 3.90 (s, 6 H, 2
.
1H NMR: δ ϭ 4.85 (d, 2J ϭ 12.5 Hz, 2 H, 2 CHaHb), 5.00 (d, 2J ϭ
12.5 Hz, 2 H, 2 CHaHb) ppm. 13C NMR: δ ϭ 76.0 (4 CCl3), 76.6
(4 CH2), 93.4 (C-1, C-4), 161.8 (4 CO) ppm. MS (EI): m/z (%) ϭ
858 [M], 683 [C11H6Cl11O6S2], 394 (1) [C7H4Cl6O4S], 362 (6)
[C7H4Cl6O4], 131 (100) [C2H2Cl3], 117 (32) [CCl3], 95 (63), 79 (34),
61 (28), 45 (24), 36 (17), 26 (3). C14H8Cl14O8S2 (864.68): calcd. C
19.45, H 0.93, Cl 57.40, S 7.42; found C 19.74, H 0.89, Cl 57.26,
S 7.68.
CH3) ppm. 13C NMR: δ ϭ 54.8 (2 CH3), C-2 signal not observed,
128.1, (C-2, C-6), 129.1 (C-3, C5), 134.6 (C-1), 135.0 (C-4), 164.2
(COO), 186.8 (COS) ppm. MS (EI): m/z (%) ϭ 272 (0.1) [M], 230
(4) [C5H7ClO4S2], 166 (7) [C5H7ClO4], 134 (5) [C4H3ClO3], 103 (1)
[C3ClO2], 79 (2) [CClS], 59 (11) [C2H3O2], 43 (100) [C2H3O].
C7H9ClO5S2 (272.73): calcd. C 30.83, H 3.33, Cl 13.00, S 23.35;
found C 30.76, H 3.19, Cl 12.96, S 23.38.
Dimethyl 2-(Benzoyldithio)-2-chloropropanedioate (5ab): Colorless
crystals, m.p. 88.5Ϫ89.0 °C. IR: ν˜ ϭ 3035 (arom. CH), 2995 (aliph.
CH), 1777 (OCϭO), 1751 (SCϭO), 1437, 1203, 1022, 949, 873,
Reaction of Bis(2,2,2-tribromoethyl) Propanedioate (1d) with SOCl2:
No reaction could be observed after up to 20 h reflux of 1d with
SOCl2 with or without pyridine as catalyst.
773, 689, 678, 643 cmϪ1 1H NMR: δ ϭ 3.90 (s, 6 H, 2 CH3),
.
7.6Ϫ8.0 (m, 5 H, ArH) ppm. 13C NMR: δ ϭ 29.0 (CH3CO), 54.7
(2 CH3O), C-2 signal not observed, 164.2 (COO), 191.8 (COS)
ppm. MS (CI): m/z (%) ϭ 352 (54) [M ϩ NH4ϩ], 335 (10) [M ϩ
Hϩ], 105 (100) [C7H5O]. C12H11ClO5S2 (334.80): calcd. C 43.05, H
3.31, S 19.16; found C 43.04, H 3.25, S 19.10.
Reaction of N,NЈ-Di-tert-butylpropanediamide (1e) with SOCl2:
N,NЈ-Di-tert-butylpropanediamide (1e)[14] (27.80 g, 130 mmol),
thionyl chloride (124 mL, 1700 mmol), and pyridine (0.20 mL,
2.6 mmol) were stirred at room temperature until TLC showed that
the reaction was complete (10 h). The reaction mixture was then
allowed to cool, filtered, and the solvents evaporated in vacuo. It
was then triturated with diethyl ether/petroleum ether (1:1). Yield
25.0 g (69%) crude product, m.p. 137Ϫ141 °C, which was recrystal-
lized from diethyl ether to give 24.0 g (66%) colorless crystals of
N,N,NЈ,NЈ-tetra-tert-butyl-1,4-dichloro-2,3-dithiabutane-1,1,4,4-
tetracarboxamide (11e). M.p. 142.5Ϫ143.5 °C. IR: ν˜ ϭ 3425 (NH),
Dimethyl 2-Chloro-2-(phenyldithio)propanedioate (5ac): Colorless
crystals, m.p. 81.5Ϫ82.0 °C. IR: ν˜ ϭ 3040 (arom. CH), 2995 (aliph.
CH), 1743 (CϭO), 1439, 1256, 1023, 744, 687 cmϪ1. 1H NMR: δ ϭ
3.90 (s, 6 H, 2 CH3), 7.6Ϫ8.0 (m, 5 H, ArH) ppm. 13C NMR: δ ϭ
54.7 (2 CH3), C-2 signal not observed, 128.1, (C-2, C-6), 129.0 (C-
3, C5), 134.5 (C-1), 135.0 (C-4), 164.1 (2 CO) ppm. MS (EI): m/z
(%) ϭ 306 (15) [M], 218 (8) [C12H10S2], 141 (100) [C6H5S2], 109 (45)
[C6H5S], 77 (29) [C6H5], 65 (18), 59 (17) [C2H3O2]. C11H11ClO4S2
(306.79): calcd. C 43.07, H 3.61, S 20.90; found C 42.95, H 3.17,
S 20.74.
1
3275 (NH), 2290 (aliph. CH), 1712 (CϭO), 1540, 1240 cmϪ1. H
NMR: δ ϭ 1.40 (s, 36 H, 12 CH3), 7.15 (br. s, 4 H, 4 NH) ppm.
13C NMR: δ ϭ 28.3 (12 CH3), 52.9 (4 Ct), 81.3 (C-1, C-4), 162.8
(4 CϭO) ppm. MS (CI): m/z (%) ϭ 559 (2) [M ϩ Hϩ], 352 (4), 245
(100). C22H40Cl2N4O4S2 (559.62): calcd. C 47.22, H 7.20, N 10.01,
S 11.46; found C 47.48, H 7.38, N 10.12, S 11.05. An X-ray single
crystal structure determination confirming the structure was per-
formed. However, the poor quality of the single crystals which
could be grown prevented a full-scale determination of the molecu-
lar dimensions.
Diethyl 2-(Benzoyldithio)-2-chloropropanedioate (5bb): Colorless
crystals, m.p. 87.5Ϫ88.5 °C. IR: ν˜ ϭ 3040 (arom. CH), 2983 (aliph.
CH), 1741 (OCϭO), 1721 (SCϭO), 1596, 1581, 1448, 1392, 1368,
1248, 1096, 1026, 1000, 879, 834, 770, 688, 643, 615 cmϪ1 1H
.
NMR: δ ϭ 1.35 (t, 3J ϭ 7.0 Hz, 6 H, 2 CH3), 4.35 (q, 3J ϭ 7.0 Hz,
4 H, 2 CH2), 7.25Ϫ8.10 (m, 5 H, ArH) ppm. 13C NMR: δ ϭ 13.9
(2 CH3), 63.9 (2 CH2), C-2 signal not observed, 127.6 (C-2, C-6),
127.8 (C-3, C5), 129.9 (C-1), 131.4 (C-4), 164.0 (2 COO), 189.5
(COS) ppm. MS (CI): m/z (%) ϭ 380 (28) [M ϩ NH4ϩ], 263 (10)
[M ϩ Hϩ], 105 (100) [C7H5O]. C14H15ClO5S2 (362.85): calcd. C
46.34, H 4.17, S 17.67; found C 45.70, H 4.19, S 17.74.
N,N-Di-tert-butyl-2-chloro-2-(chlorothio)propanediamide (2e): N,N-
Di-tert-butylpropanediamide (1e)[14] (8.35 g, 390 mmol) was sus-
pended in benzene (250 mL). Sulfur dichloride (17.7 mL,
279 mmol) was added, evolution of hydrogen chloride occurred im-
mediately, and the mixture formed a thick paste. Benzene (75 mL)
was added and the mixture heated at reflux until TLC showed that
the reaction was complete (4.5 h). The cooled mixture was filtered. Diethyl 2-Chloro-2-(phenyldithio)propanedioate (5bc): Colorless
Yield 8.70 g (71%) of crude product, m.p. 141Ϫ146 °C, which was
recrystallized from benzene to give 2e. Final yield 7.50 g (61%) of
pale yellow needles, m.p. 147.5Ϫ148.5 °C. IR: ν˜ ϭ 3287 (NH), 2976
(aliph. CH), 1704 (CϭO), 1511, 1394, 1364, 1215, 946, 834, 631 6 H, 2 CH3), 4.35 (q, J ϭ 7.0 Hz, 4 H, 2 CH2), 7.50 Ϫ7.95 (m, 5
cmϪ1. 1H NMR: δ ϭ 1.40 (s, 18 H, 6 CH3), 6.80 (br. s, 2 H, 2 NH) H, ArH) ppm. 13C NMR: δ ϭ 13.9 (2 CH3), 63.9 (2 CH2), C-2
ppm. 13C NMR: δ ϭ 28.3 (6 CH3), 52.9 (2 Ct), 81.3 (C-2), 162.8 signal not observed, 127.8 (C-2, C-6), 127.9 (C-3, C5), 129.6 (C-1),
crystals, m.p. 69.5Ϫ70.0 °C. IR: ν˜ ϭ 3030 (arom. CH), 2983 (aliph.
CH), 1742 (CϭO), 1576, 1477, 1440, 1368, 1251, 1095, 1024, 895,
1
3
857, 788, 743, 688, 668 cmϪ1. H NMR: δ ϭ 1.35 (t, J ϭ 7.0 Hz,
3
(2 CO), ppm. C11H20Cl2N2O2S (315.26): calcd. C 41.91, H 6.39, N
8.86, S 10.17; found C 42.06, H 6.54, N 8.90, S 10.78.
131.4 (C-4), 164.0 (2 CO) ppm. MS (EI): m/z (%) ϭ 334 (16) [M],
261 (1) [C10H10ClO2S2], 218 (18) [C12H10S2], 197 (7), 141 (100)
Eur. J. Org. Chem. 2002, 2039Ϫ2045
2043

A. Senning et al.
[C6H5S2], 109 (57) [C6H5S], 77 (20) [C6H5], 65 (20), 45 (14), 29 (21). 100 mL water and finally dried over anhydrous magnesium sulfate.
FULL PAPER
C13H15ClO4S2 (334.84): calcd. C 46.63, H 4.52, S 19.15; found C
46.50, H 4.47, S 19.95.
Filtration and subsequent evaporation of the ether yielded 0.75 g
(88%) of tetramethyl 1,4-dichloro-2,3-dithiabutane-1,1,4,4-tetra-
carboxylate (11a), m.p. 72.0Ϫ72.5 °C (vide supra).
Reactions of 2e with Mercapto Compounds: When 2e was treated
with thioacetic acid, thiobenzoic acid, or thiophenol under the
above-mentioned conditions the only isolated propanedioic acid
When 2b (1.00 g, 3.85 mmol) was reduced as above the yield of 11b
was 0.80 g (81%), m.p. 52.5Ϫ53.0 °C (ref.[13] m.p. 51.5Ϫ52.0 °C).
derivative was 1e[13] in 94%, 61%, and 75% yield, respectively. In Current consumption 749 C, calculated for a 2-electron process
the second case the co-product was dibenzoyl trisulfide,[15] in the
third case diphenyl disulfide.[16]
742 C.
d) With Sodium Trithiocarbonate: A general procedure was fol-
lowed.[21] Sodium trithiocarbonate[21] (1.50 g, 10 mmol) was dis-
solved in 10 mL water and 2 (10 mmol), dissolved in 20 mL dichloro-
methane, was added, with stirring, at 0 °C. When the red color of
Substitution/Reduction of 2. a) With p-Toluenesulfinate Ions: A gen-
eral procedure[17] was followed. A two-phase mixture of sodium p-
toluenesulfinate dihydrate (2.20 g, 10 mmol), 2 (10 mmol), tetrabu-
tylammonium hydrogen sulfate (0.20 g), 25 mL water, and 25 mL the aqueous phase had disappeared the organic layer was separ-
benzene was stirred at room temperature until TLC showed that ated, washed with water, and dried overnight over anhydrous cal-
the reaction was complete (5 h). The benzene phase was washed
three times with water and dried over anhydrous calcium chloride.
After evaporation in vacuo the residue was column chromato-
graphed. The following products (in the order of elution) were ob-
cium chloride and charcoal. The products were isolated by evapora-
tion in vacuo and subsequent column chromatography. We ob-
tained 10a, m.p. 165.0Ϫ166.5 °C (ref.[13] m.p. 164.5Ϫ165.5 °C)
(from 2a, yield 86%), 10b (from 2b, yield 71%), and 9e (from 2e,
tained: from 2a: 12a (1.40 g, 40%), 11a (0.30 g, 17%), 9a, m.p. 57.0 yield 56%).
Ϫ58.5 °C (0.55 g, 28%); from 2e: 11e (1.80 g, 65%), 9e (0.60 g,
Chlorination of 11: Sulfuryl chloride (1.00 mL, 10 mmol) was added
dropwise to a stirred solution of 11 (10 mmol) in 30 mL tetrachloro-
23%).
Dimethyl 2-Chloro-2-(p-tolylsulfonylthio)propanedioate (12a): Col-
methane. When TLC showed that the reaction was complete (3 h)
orless crystals, m.p. 89.5Ϫ90.5 °C. IR: ν˜ ϭ 3040 (arom. CH), 2995 the reaction solvents were evaporated in vacuo and the residue col-
(aliph. CH), 1744 (CϭO), 1593, 1429, 1339, 1267, 1147, 1079, 1013, umn chromatographed. We thus obtained 2a (from 11a, yield 93%),
946, 848, 817, 764, 700, 653, 587, 519 cmϪ1. H NMR: δ ϭ 2.55
2b (from 11b,[13] yield 89%), as well as (in the order of elution) 2e
1
(s, 3 H, CH3), 3.95 (s, 6 H, 2 CH3), 7.35 (d, 3J ϭ 8.0 Hz, 2 H, and 14e (from 11e, yields 29% and 69%, respectively).
ArH), 7.85 (d, J ϭ 8.0 Hz, 2 H, ArH) ppm. 13C NMR: δ ϭ 21.8
N,NЈ-Di-tert-butyl-2,2-dichloropropanediamide (14e): Colorless
3
˜
(CH3Ar), 54.2 (2 CH3), C-2 signal not observed, 128.3 (C-3, C-5), crystals, m.p. 98.0Ϫ99.0 °C. IR: ν ϭ 3310 (NH), 2983 (aliph. CH),
129.9 (C-2, C-6), 141.5 (C-1), 146.1 (C-4), 163.3 (2 CϭO) ppm. MS
1690 (CϭO), 1521, 1455, 1363, 1265, 1217, 943, 868, 836, 597
1
(EI): m/z (%) ϭ 352 (0.2) [M], 293 (0.2) [C10H10ClO4S2)], 265 (2), cmϪ1. H NMR: δ ϭ 1.40 (s, 18 H, 6 CH3), 6.9 (br. s, 2 H, 2 NH)
254 (0.3), 229 (2), 221 (0.2), 162 (45) [C5H6O4S], 155 (38) ppm. 13C NMR: δ ϭ 28.0 (6 CH3), 52.8 (Ct), 80.8 (C-2), 161.9 (2
[C7H7O2S], 139 (10) [C7H7OS], 103 (18), 91 (100) [C7H7], 65 (26),
59 (46) [C2H3O2], 45 (15), 39 (8), 29 (2). C12H13ClO6S2 (352.20): C11H20Cl2N2O2 (283.20): calcd. C 46.65, H 7.12, N 9.89; found C
calcd. C 40.85, H 3.71, S 18.18; found C 41.09, H 3.62, S 18.31. 46.08, H 7.26, N 9.86.
CϭO) ppm. MS (CI): m/z (%) ϭ 283 (100) [M ϩ
Hϩ].
N,N,NЈ,NЈ-Tetra-tert-butyl-1,2,4-trithiolane-3,3,5,5-tetracarbox- Chlorination of 9: Sulfuryl chloride (2.00 mL, 20 mmol) was added
amide (9e): Colorless crystals, m.p. 76.5Ϫ77.5 °C. IR: ν˜ ϭ 3304 dropwise to a stirred solution of 9 (10 mmol) in 30 mL tetrachloro-
(NH), 2967 (aliph. CH), 1688 (CϭO), 1652, 1527, 1458, 1393, 1366, methane at room temperature. The mixture was stirred until TLC
1
1273, 1221, 825, 623, 476 cmϪ1. H NMR: δ ϭ 1.35 (s, 36 H, 12
showed that the reaction was complete (3 h). After evaporation in
CH3), 7.55 (br. s, 4 H, 4 NH) ppm. 13C NMR: δ ϭ 28.4 (12 CH3), vacuo the residue was column chromatographed. The following
52.6 (4 Ct), C-3, C-5 signals not observed, 164.2 (4 CO) ppm. MS products (in the order of elution) were obtained: from 9a: 2a
(CI): m/z (%) ϭ 521 (22) [M ϩ Hϩ], 229 (100). C22H40N4O4S3
(520.78): calcd. C 50.74, H 7.74, N 10.76, S 18.47; found C 50.94,
H 7.70, N 10.58, S 18.14. A single crystal structure determination
was performed (vide supra).
(1.10 g, 47%) and dimethyl 2,2-bis(chlorothio)propanedioate
(15a)[22] (1.30 g, 49%); from 9e: 2e (0.80 g, 26%) and 14e (1.60 g,
57%).
Reaction of 2 with Sulfur: Compound 2 (10 mmol) and elemental
sulfur (0.32 g, 10 mmol) were fused together at 190 °C under a
reflux condenser until TLC showed that the reaction was complete
(6 h), then evaporated to dryness and the residue column chroma-
tographed. The following products (in the order of elution) were
obtained: from 2a: 9a (0.35 g, 20%), 11a (0.30 g, 15%) and 12a
(1.10 g, 52%); from 2b: 11b[13] (1.70 g, 76%); from 2e: 9e (0.70 g,
27%), 11e (1.10 g, 39%) and 14e (0.70 g, 25%).
b) With Potassium Iodide, Triphenylphosphane,[18] Sodium Azide, Ti-
n(II) Chloride,[19] or Magnesium: The sulfenyl chlorides 2 were
cleanly and in good yields reduced to the disulfides 11 by potas-
sium iodide in acetonitrile, by triphenylphosphane in toluene, by
sodium azide in DMF, by tin(II) chloride in dichloromethane/37%
HCl, and by magnesium turnings in ether.
c) Electrochemical Reduction: Compound 2a (1.00 g, 4.29 mmol)
was reduced in an H cell at a platinum net electrode in 30 mL of
an argon deaerated 0.1  solution of tetrabutylammonium tetra-
Reaction of 5ab with Morpholine: Compound 5ab (6.70 g, 20 mmol)
was dissolved in 50 mL diethyl ether, cooled in an ice bath, and
fluoroborate in N,N-dimethylformamide.[20] A graphite electrode treated, with stirring, with morpholine (10.4 mL, 120 mmol), dis-
was used as anode. The potential was fixed at 0 V vs. Ag/AgI,
0.1  I in DMF, and the temperature of the cell kept at ambient
temperature (22 °C) by means of a water bath. After the consump-
tion of 837 C (calculated 831 C, n ϭ 2) the current stopped and
the catholyte solution was poured into 1000 mL water and ex-
tracted with 250 mL ether. The ether phase was washed twice with
solved in 25 mL diethyl ether. The rate of the addition was adjusted
so as to prevent any appreciable rise in the temperature of the reac-
tion mixture. The reaction mixture was extracted three times with
water, the organic phase dried over anhydrous calcium chloride,
filtered, and the solvents evaporated in vacuo. The remaining crude
product was column chromatographed. The following products (in
2044
Eur. J. Org. Chem. 2002, 2039Ϫ2045

2-Chloro-2-(chlorothio)propanedioic Diesters and Diamides
FULL PAPER
[7]
For more recent work see: M. I. Hegab, F. M. E. Abdel-Meg-
eid, F. A. Gad, S. A. Shiba, I. Søtofte, J. Møller, A. Senning,
Acta Chem. Scand. 1998, 53, 133Ϫ141; F. A. G. El-Essawy, S.
M. Yassin, I. A. El-Sakka, A. F. Khattab, I. Søtofte, J. Ø.
Madsen, A. Senning, J. Org. Chem. 1998, 64, 9840Ϫ9845; A.
Ishii, T. Nakaniwa, K. Umezawa, J. Nakayama, Tetrahedron
1999, 55, 10341Ϫ10350; K. Shimada, K. Kodaki, S. Aoyagi, Y.
Takikawa, C. Kabuto, Chem. Lett. 1999, 695Ϫ698; A. Ishii, J.
Nakayama, Rev. Heteroatom Chem. 1999, 19, 1Ϫ33; for an
early study describing the amazingly straightforward dechloro-
thiation of 1-chloroethanesulfenyl chloride with sodium sulfide
nonahydrate in DMF not previously quoted by contemporary
workers in the fields of thiosulfine (3) and dithiirane (4) chem-
istry see: P. Dubs, M. Joho, Helv. Chim. Acta 1978, 61,
1404Ϫ1406.
the order of elution) were obtained: tetramethyl 1,2,4-trithiolane-
3,3,5,5-tetracarboxylate (9a) (0.50 g, 28%), tetramethyl 1,2,4,5-
tetrathiane-3,3,6,6-tetracarboxylate (10a) (0.50 g, 26%), tetra-
methyl 1,4-dichloro-2,3-dithiabutane-1,1,4,4-tetracarboxylate (11a)
(0.65 g, 33%).
X-ray Crystal Structure Determination of 11a: Data were collected
at 296 K on a SMART diffractometer using Mo-Kα radiation. The
crystal-to-detector distance was 4.5 cm. The structures were solved
by direct methods (SHELXTL) and refined with a full-matrix least-
squares technique. All hydrogen atoms were at calculated positions
using a riding model with CϪH ϭ 0.96Ϫ0.97 and fixed thermal
parameters [U(H) ϭ 1.2 times U for attached CM; see Table 2 for
the crystallographic data].
CCDC-183065 (11a) contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge at
www.ccdc.cam.ac.uk/conts/retrieving.html [or from the Cambridge
Crystallographic Data Centre, 12, Union Road, Cambridge
CB2 1EZ, UK; Fax: (internat.) ϩ44-1223/336-033; E-mail:
deposit@ccdc.cam.ac.uk].
[8]
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R. Schubart, Houben-Weyl E11, 88Ϫ89 (1985).
[10]
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L. Fisera, R. Huisgen, I. Kalwinsch, E. Langhals, X. Li, G.
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Acknowledgments
A grant from the Egyptian Ministry of Higher Education and from
Menoufia University under the Channel System to M. A. Hawata
is gratefully acknowledged. This work was also supported by the
Danish Research Councils (SNF). Professor Torben Lund, Ros-
kilde University, kindly supervised the electrochemical experiments.
The technical support of Mrs. Jytte Grove-Rasmussen and of Mrs.
Ulla Maxmiling, Department of Chemistry, Technical University
[14]
[15]
[16]
[17]
´
of Denmark is gratefully acknowledged. Professor G. Mloston,
Łodz, Poland was a highly appreciated discussion partner.
[1]
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[O02002]
Eur. J. Org. Chem. 2002, 2039Ϫ2045
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