Selective synthesis of bis[1,2]dithiolo[1,4]thiazines from 4-isopropylamino-5-chloro-1,2-dithiole-3-ones

Article abstract of DOI:10.1016/j.tetlet.2007.06.071

Reaction of 4-isopropylamino-5-chloro-1,2-dithiole-3-ones 3 and S₂Cl₂ in acetonitrile gave selectively 3-oxo-bis[1,2]dithiolo[1,4]thiazine-5-thiones 1 by the addition of triethylamine and bis[1,2]dithiolo[1,4]thiazine-3,5-diones 5 un

Full text of DOI:10.1016/j.tetlet.2007.06.071

Tetrahedron Letters 48 (2007) 5851–5854
Selective synthesis of bis[1,2]dithiolo[1,4]thiazines from
4-isopropylamino-5-chloro-1,2-dithiole-3-ones
Lidia S. Konstantinova, Andrej A. Berezin, Kirill A. Lysov and Oleg A. Rakitin*
N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect, 47, Moscow 119991, Russia
Received 7 May 2007; revised 5 June 2007; accepted 14 June 2007
Available online 20 June 2007
Abstract—Reaction of 4-isopropylamino-5-chloro-1,2-dithiole-3-ones 3 and S2Cl2 in acetonitrile gave selectively 3-oxo-bis[1,2]di-
thiolo[1,4]thiazine-5-thiones 1 by the addition of triethylamine and bis[1,2]dithiolo[1,4]thiazine-3,5-diones 5 under the action of
formic acid. 3,5-Diones 5 were also obtained by intramolecular cyclization of N,N-bis(5-chloro-3-oxo[1,2]dithiol-4-yl)amines 6 with
S2Cl2 in the presence of Et3N.
Ó 2007 Elsevier Ltd. All rights reserved.
Compounds containing 3H-1,2-dithiole-3-thione and 3-
one fragments are of current interest since they have a
broad spectrum of biological activity and may be useful
synthons for many sulfur heterocycles. Oltipraz (4-
methyl-5-(2-pyrazinyl)-1,2-dithiole-3-thione) has been
clinically tested as a preventive agent against various
types of cancer.1 Anethole dithiolethione (Sulfarlem, 5-
found to be the most useful compound from a synthetic
point of view.8 Ketothiones 1 could also be of interest as
biologically active substances containing potentially bio-
logically active 1,2-dithiole-3-thione and 3-one moieties
in one molecule.
Unfortunately, ketothiones 1 are less accessible from
other bisdithiolothiazines; only an N-ethyl derivative
can be prepared from N-ethyldiisopropylamine, S2Cl2
and cyclopenten-1-yl-acetic acid, selectively, and in
moderate yield.5 Other ketothiones 1 were synthesized
from non-commercial N-substituted diisopropylamines,
as a rule, in low yields and in mixtures with other bis-
dithiolothiazines. Monocyclic 5-mercapto-1,2-dithiole-
3-thiones 2, which we have recently obtained,9 show
high promise as synthons for the preparation of bisdi-
thiolothiazine ketothiones 1. Yet, on reaction with a
mixture of S2Cl2 and DABCO under the conditions
employed for preparing tricyclic bis(dithiolo)thiazines
from substituted diisopropylamines,5 5-chlorodithiol-3-
ones 3 were generated in high yields.9 In this Letter we
report a selective synthesis of bisdithiolothiazine keto-
thiones and diones from 5-chloro-1,2-dithiole-3-ones;
the unique feature of these transformations is electro-
philic substitution of chlorine attached to the dithiole
ring by sulfur upon treatment with sulfur monochloride.
(4-methoxyphenyl)-3H-1,2-dithiole-3-thione),
a clini-
cally available pluripotent antioxidant, has been recently
proposed as a neuroprotectant for Parkinson’s disease.
Also, it has various applications in human therapy for
its choleretic and sialogogic properties and as a cytopro-
tective agent in lung precancerous lesions prevention in
smokers.2 1,2-Dithiole-3-thiones were considered as
potent bacterial inhibitors of enzyme Fabh from
Escherichia coli and Staphylococcus aureus.3 Apart from
their biological activities, dithiolethiones have been
intensively investigated in 1,3-dipolar cycloaddition
reactions with dipolarophiles.4
With a view to discovering new materials we have
described the new polycyclic dithiole derivatives,
bis[1,2]dithiolo[1,4]thiazines,5 bis[1,2]dithiolopyrroles,6
and [1,2]dithiolo[1,4]thiazine.7 Bisdithiolothiazine keto-
thione (1, R = Et) bearing reactive thione and activating
and chemically inert keto groups in one molecule was
We have found that 5-chloro-1,2-dithiol-3-ones 3 could
be synthesized directly from the corresponding diiso-
propylamines, S2Cl2 and DABCO in moderate to high
yields using a modified method9 at low temperature
(ꢀ15 °C) and further treatment with formic acid
Keywords: Bis[1,2]dithiolo[1,4]thiazine-5-thiones; Sulfur monochlo-
ride; Intramolecular cyclization; 1,2-Dithiole-3-ones.
*
Corresponding author. Tel.: +7 495 1355327; fax: +7 495 1355328;
e-mail: orakitin@ioc.ac.ru
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.06.071

5852
L. S. Konstantinova et al. / Tetrahedron Letters 48 (2007) 5851–5854
R
N
R
N
R
N
R
N
O
S
R
N
S2Cl2/DABCO
HCO2H
S2Cl2/DABCO
HCO2H
O
O
S
O
HCO H
2
S
+ S Cl /DABCO
2
2
S
S
S
S
eCN
M
S
S
S
S
S
5
l
C
HS
Cl
% yield
3
3
2
a R = CH2CH2Phth
b R = CH2CH2Cl
c R = CH2CH2N3
d R = CH2CH2CO2Et
e R = CH2CH2SPh
67
45
45
55
72
47
R = CH2Ph
% yield
54
R = CH2CH2CO2Et
R = CH2CH2CN
R = CH2CH2N3
a R = CH CH Phth
2
2
b R = CH CH Cl
78
58
O
2
2
c R = CH CH N
2
2 3
f
R = CH2CH2CN
d R = CH CH CO Et 65
N
Phth =
2
2
2
g R = CH2CH2SO2Ph 64
h R = CH2CH2OC(O)H 45
e R = CH CH SPh
56
49
41
2
2
f R = CH CH CN
O
i
R = CH2Ph
48
2
2
i R = CH Ph
2
Scheme 1. Synthesis of 4-isopropylamino-5-chloro-1,2-dithiole-3-ones
3.
Scheme 3. Synthesis of bis[1,2]dithiolo[1,4]thiazine-3,5-diones 5.
R
R
(Scheme 1). Thus we decided to use dithioles 3 as start-
ing materials for the synthesis of bisdithiolothiazines.
O
Cl
O
N
N
MeCN
+ S2Cl2 /DABCO
S
+S
S
The reaction of dithiolone 3a with S2Cl2 and DABCO
was investigated in detail; the nature of the solvent used
appeared crucial for a successful reaction. If the reaction
was carried out in inert solvents such as chloroform,
dichloromethane or 1,2-dichloroethane, the starting
dithiolone 3a was isolated in practically quantitative
yield. Attempts to employ other solvents recently used
in reactions with sulfur monochloride (THF10 or
DMF11) failed. Treatment of S2Cl2 and DABCO in ace-
tonitrile—a solvent, which is rarely used in S2Cl2 reac-
tions—gave bisdithiolothiazine ketothione 1a after
treatment with triethylamine as a base (Scheme 2).
_
S
S
S
S
Cl
l
C
3
4
g R = CH2CH2SO2Ph
h R = CH2CH2OC(O)H
l
C
O
O
N
HCO2H, HCl
S
S
S
S
S
5b
Scheme 4. Reaction of chloroketones 3g and 3h with S2Cl2 and
DABCO.
We then extended this reaction to other N-substituted 4-
isopropylamino-5-chloro-1,2-dithiole-3-ones 3. Bisdi-
thioloketothiones 1 were obtained selectively in all
reactions in moderate to high yields (Scheme 2).12 We
believe this to be the first case where a chloro substituent
is replaced by sulfur under the eletrophilic action of sul-
fur monochloride and a base. Presumably the key inter-
mediate in the reaction is 3-chlorodithiolium salt 4,
which gave thiones 1 with sulfur nucleophiles generated
from a base (e.g., triethylamine) and sulfur formed in
the ongoing reaction.5 It was envisaged that an oxygen
nucleophile (the most frequently used being formic acid)
on reaction with 3 could give diketones 5. We checked
this possibility by replacing Et3N with formic acid at
the last step and found that diketones 5 were prepared
selectively in moderate yields (Scheme 3).
Treatment of chloroketones 3g and 3h with S2Cl2 and
DABCO in acetonitrile followed by addition of formic
acid resulted in chloroethyl derivative 5b isolated in
low yields (15–20%). Presumably, the phenylsulfonyl
and formyloxy groups are sensitive to attack of hydro-
chloric acid formed from S2Cl2 and HCO2H to give
chloroethyl bisdithiolothiazine 5b (Scheme 4).
Interesting results were obtained when chloroketones
were treated with a mixture of S2Cl2 and DABCO where
DABCO is in deficiency relative to S2Cl2 (S2Cl2/DAB-
CO ratio = 2:1). In the cases examined bis(dithiol-
yl)amines 6 were isolated in moderate yields (Scheme
5). Apparently the reaction with this ratio of reagents,
R
R
N
O
Cl
O
S
N
eC
M
N
+ S2Cl2 /DABCO
+
S
S
S
S
S
_
Cl
R
N
O
Cl
l
C
R
N
l
C
O
3
7
eC
N
M
S
+ S2Cl2 /DABCO
+
S
S
S
R
N
R
O
N
_
l
O
C
O
l
C
S
S
S
Cl
[O]
S2Cl2
3
4
+
S
S
S
S
S
S
_
S
S
% yield
68
Cl
Cl Cl
Cl Cl
a R = CH2CH2Phth
b R = CH2CH2Cl
c R = CH2CH2N3
d R = CH2CH2CO2Et
e R = CH2CH2SPh
R
O
S
40
65
73
54
49
44
6
8
N
Et3N
% yield
44
41
S
S
a R = CH2CH2Phth
c R = CH2CH2N3
d R = CH2CH2CO2Et 51
i R = CH2Ph 46
S
S
S
f
R = CH2CH2CN
1
g R = CH2CH2SO2Ph
h R = CH2CH2OC(O)H 78
R = CH2Ph 62
i
Scheme 5. Synthesis of N,N-bis(5-chloro-3-oxo[1,2]dithiol-4-yl)amines
6.
Scheme 2. Synthesis of 3-oxo-bis[1,2]dithiolo[1,4]thiazine-5-thiones 1.

L. S. Konstantinova et al. / Tetrahedron Letters 48 (2007) 5851–5854
5853
amines in selectivity and yields.8 The novelty of these
transformations is in replacing chlorines by sulfur in
the reaction with electrophilic sulfur monochloride and
its mixtures with tertiary amines. The key steps may
be explained by the addition of sulfur monochloride into
C–H or C–Cl bonds with further extrusion of SCl2 from
intermediates 9 or 10 (Scheme 7), as explained for poly-
sulfur chain extension in the formation of pentathie-
pins.15 The described experimental procedures may
serve as an efficient basis for new syntheses of sulfur
compounds from readily available chloro derivatives.
R
R
N
O
S
O
O
O
N
CHCl3
S
+ S2Cl2/Et3N
S
S
S
S
S
S
S
Cl Cl
6
5
% yield
95
a R = CH2CH2Phth
d R = CH2CH2CO2Et
e R = CH2CH2SPh
f R = CH2CH2CN
i R = CH2Ph
82
87
80
79
j R = Et
93
Scheme 6. Cyclization of N,N-bis(5-chloro-3-oxox[1,2]dithiol-4-yl)-
amines 6 into bis[1,2]dithiolo[1,4]thiazine-3-5-diones 5.
Acknowledgement
instead of undergoing ring closure to tricycles 1 or 5, led
to the formation of intermediate salt 7, which was fur-
ther chlorinated by excess S2Cl2 to give salt 8, the latter
then being converted to bis(dithiolyl)amines 6 with
oxygen donors. Although bisdithiolylamines 6 were
obtained in moderate yields, they were formed selec-
tively, but not in mixtures with bisdithiolothiazines as
described previously.13
We gratefully acknowledge financial support from the
Russian Foundation for Basic Research (Grant No.
05-03-32032).
Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/
j.tetlet.2007.06.071.
In an attempt to extend the S2Cl2 sulfurating ability in
reactions with 5-chloro-1,2-dithioles, we investigated
the reaction N,N-bis(5-chloro-3-oxo[1,2]dithiol-4-yl)-
amines 6 with sulfur monochloride and a base. DABCO
was found to be inert in this reaction, which was not sur-
prising bearing in mind that bicyclic compounds 6 were
formed in the presence of DABCO (see Scheme 5 and
data in Ref. 13). Treatment of 6 with S2Cl2 and triethyl-
amine in chloroform for 3 d at room temperature
followed by heating under reflux for 3 h gave bisdithiol-
othiazines 5 in high yields (Scheme 6). The best results
were obtained when Et3N was present in threefold
excess with respect to S2Cl2.
References and notes
1. (a) Glintborg, B.; Weimann, A.; Kensler, T. W.; Poulsen,
H. E. Free Radical Biol. Med. 2006, 41, 1010–1014; (b)
Sharma, S.; Gao, P.; Steele, V. E. Carcinogenesis 2006, 27,
1721–1727; (c) Iida, K.; Itoh, K.; Kumagai, Y.; Oyasu, R.;
Hattori, K.; Kawai, K.; Shimazui, T.; Akaza, H.;
Yamamoto, M. Cancer Res. 2004, 64, 6424–6431.
2. (a) Drukarch, B.; Flier, J.; Jongenelen, C. A. M.;
Andringa, G.; Schoffelmeer, A. N. M. J. Neural Trans-
mission 2006, 113, 593–598; (b) Pouzaud, F.; Christen,
M.-O.; Warnet, J.-M.; Rat, P. Pathologie Biologie 2004,
52, 308–313.
3. He, X.; Reeve, A. M.; Desai, U. R.; Kellogg, G. E.;
Reynolds, K. A. Antimicrob. Agents Chemother. 2004, 48,
3093–3102.
4. (a) Pedersen, C. Th. Adv. Heterocycl. Chem. 1982, 31, 63–
113; (b) McKinnon, D. M. In Comprehensive Heterocyclic
Chemistry II; Katritzky, A. R., Rees, C. W., Scriven, E. F.
V., Eds.; Pergamon: Oxford, 1996; Vol. 3, Chapter 3.11;
(c) Pedersen, C. Th. Sulfur Rep. 1995, 16, 173–221.
All new compounds were fully characterized by elemen-
1
tal analysis, H and 13C NMR, IR spectroscopy and
mass spectrometry, and some by HMRS.
The reactions described provide new and efficient routes
to bis(dithiolo)thiazines and bis(dithiolyl)amines, some
of which have marked activity against various cancer
lines.14 The conversion of chlorodithiolones 3 into
unsymmetrical bisdithiazolothiazine ketothiones 1 in
acetonitrile surpasses their synthesis from diisopropyl-
R
N
R
R
N
R
N
R
O
S
O
S
X
O
Cl
S
Cl
S
Cl
S
O
O
N
N
S Cl
nucl.
2
2
S Cl
2
2
+
S
+
S
S
S
+
S
S
_
S
S
- SCl
S
S
S
S
S
2
S
_
S
Cl
Cl
_
Cl
S
S
Cl
Cl
Cl
2, X = S
5, X = O
3
7
9
4
Cl
R
N
R
R
N
O
O
O
O
O
O
S Cl
S Cl
2
2
2
N
2
5
S
S
S
S
S
S
S
S
- SCl
- SCl
- SCl
2
2
2
S
S
S
S
S
S
Cl
10
S
Cl
Cl Cl
Cl
Cl
6
Scheme 7. A plausible mechanism for the formation of bisdithiolothiazines 2 and 5.

5854
L. S. Konstantinova et al. / Tetrahedron Letters 48 (2007) 5851–5854
5. Rees, C. W.; White, A. J. P.; Williams, D. J.; Rakitin, O.
crystals, mp 159–160 °C. Anal. Calcd for C14H9NOS7: C,
38.95; H, 2.10; N, 3.24. Found: C, 38.76; H, 2.05; N, 3.43.
1H NMR (250 MHz, Py-d5) d: 3.43 (2H, t, J 6.7, CH2),
4.58 (2H, t, J 6.6, CH2), 7.21 (3H, m, Ph), 7.45 (2H, m,
Ph). 13C NMR (75.5 MHz, Py-d5) d: 33.1 and 45.9 (2CH2),
126.5 (CH, Ph), 129.3 (2CH, Ph), 129.6 (2CH, Ph), 135.9,
136.8, 147.7, 158.3 and 163.1 (5 sp2 tertiary C), 183.3
(C@O), 202.6 (C@S). MS (EI, 70 eV), m/z (%): 431 (M+,
15), 399 (31), 263 (57).
A.; Marcos, C. F.; Polo, C.; Torroba, T. J. Org. Chem.
1998, 63, 2189–2196.
6. Marcos, C. F.; Polo, C.; Rakitin, O. A.; Rees, C. W.;
Torroba, T. Chem. Commun. 1997, 879–880.
7. Rees, C. W.; White, A. J. P.; Williams, D. J.; Rakitin, O.
A.; Konstantinova, L. S.; Marcos, C. F.; Torroba, T. J.
Org. Chem. 1999, 64, 5010–5016.
8. (a) Barriga, S.; Fuertes, P.; Marcos, C. F.; Miguel, D.;
Rakitin, O. A.; Rees, C. W.; Torroba, T. J. Org. Chem.
2001, 66, 5766–5771; (b) Amelichev, S. A.; Barriga, S.;
Konstantinova, L. S.; Markova, T. B.; Rakitin, O. A.;
Rees, C. W.; Torroba, T. J. Chem. Soc., Perkin Trans. 1
2001, 2409–2413; (c) Barriga, S.; Fuertes, P.; Marcos, C.
F.; Rakitin, O. A.; Rees, C. W.; Torroba, T. J. Org. Chem.
2002, 67, 6439–6448; (d) Garcia, N.; Fuertes, P.; Barriga,
S.; Neo, A. G.; Miguel, D.; Torroba, T. Heterocycles 2003,
60, 1083–1094.
3-(3-Oxo-5-thioxo-3H,4H,5H-bis[1,2]dithiolo[3,4-b:40,30-
e][1,4]thiazin-4-yl)propanenitrile 1f, yield 49%. Red crys-
tals, mp 196–197 °C. Anal. Calcd for C9H4N2OS6: C,
31.01; H, 1.16; N, 8.04. Found: C, 31.09; H, 1.19; N, 8.28.
1H NMR (250 MHz, Py-d5) d: 3.03 (2H, t, J 6.2, CH2),
4.62 (2H, t, J 5.9, CH2). 13C NMR (75.5 MHz, Py-d5) d:
17.4 and 43.2 (2CH2), 118.9 (CN), 122.1, 146.6, 151.5 and
159.2 (4 sp2 tertiary C), 183.4 (C@O), 202.6 (C@S). MS
(EI, 70 eV), m/z (%): 348 (M+, 79), 316 (11).
9. (a) Konstantinova, L. S.; Rakitin, O. A.; Rees, C. W.
Mendeleev Commun. 2001, 165–166; (b) Konstantinova, L.
S.; Berezin, A. A.; Lysov, K. A.; Rakitin, O. A. Russ.
Chem. Bull., Int. Ed. 2006, 55, 143–147.
10. Rakitin, O. A.; Rees, C. W.; Williams, D. J.; Torroba, T.
J. Org. Chem. 1996, 61, 9178–9185.
4-[2-(Phenylsulfonyl)ethyl]-5-thioxo-3H,4H,5H-bis[1,2]-
dithiolo[3,4-b:40,30-e][1,4]thiazin-3-one 1g, yield 44%.
Red crystals, mp 113–115 °C. Anal. Calcd for C14H9-
NO3S7: C, 36.26; H, 1.96; N, 3.02. Found: C, 36.02; H,
2.06; N, 3.24. 1H NMR (250 MHz, Py-d5) d: 3.92 (1H, t, J
5.4, CH2), 4.44 (1H, t, J 5.4, CH2), 4.56 (2H, br s, CH2),
7.48 (3H, m, Ph), 7.83 (2H, m, Ph). 13C NMR (75.5 MHz,
Py-d5) d: 46.9 and 63.4 (2CH2), 125.4 (2CH, Ph), 129.5
(2CH, Ph), 132.6 (CH, Ph), 128.4, 137.0, 145.2, 148.0 and
158.6 (5 sp2 tertiary C), 183.6 (C@O), 202.7 (C@S). MS
(EI, 70 eV), m/z (%): 431 (M+ꢀS, 3), 322 (MꢀSO2Ph, 4),
306 (15).
11. Plater, M. J.; Rees, C. W.; Roe, D. G.; Torroba, T. J.
Chem. Soc., Perkin Trans. 1 1993, 769–774.
12. General procedure for the preparation of 1 and 5 from 3.
Disulfur dichloride (2 mmol) was added dropwise at ꢀ25
to ꢀ35 °C to a stirred solution of DABCO (2 mmol) in
acetonitrile (20 ml) under argon. The corresponding N-
substituted 4-isopropylamino-5-chloro-1,2-dithiole-3-one
3 (0.2 mmol) in acetonitrile (2 ml) was added and the
mixture was stirred at rt for 2 h. Then Et3N (2 mmol) for
the synthesis of 1 or HCO2H (40 mmol) for the synthesis
of 5 was added, the mixture was refluxed for 3 h, filtered
and the solvents were evaporated. The residue was
separated by column chromatography (Silica gel Merck
60, light petroleum and then light petroleum–CH2Cl2
mixtures). Bisdithioloketothiones 1b (yield 40%), 1d (yield
73%), 1i (yield 62%) and bisdithioloketothiones 5a (yield
54%), 5b (yield 78%), 5d (yield 65%), 5e (yield 56%) and 5i
(yield 41%) are identical with the known compounds.
2-[2-(3-Oxo-5-thioxo-3H,4H,5H-bis[1,2]dithiolo[3,4-b:40,
30-e][1,4]thiazin-4-yl)ethyl]-1H-isoindole-1,3(2H)-dione
1a, yield 68%. Red crystals, mp 216–217 °C. Anal. Calcd
for C16H8N2O3S6: C, 41.01; H, 1.72; N, 5.98. Found: C,
41.24; H, 1.50; N, 5.90. C16H8N2O3S6 requires M,
467.8859. Found M+, 467.8859. 1H NMR (250 MHz,
Py-d5) d: 3.96 (2H, t, J 6.6, CH2), 4.77 (2H, br s, CH2),
7.42 (2H, m, Ar), 7.65 (2H, m, Ar). 13C NMR (75.5 MHz,
Py-d5) d: 38.1 and 43.8 (2CH2), 132.5, 136.6, 147.2, 149.4
and 157.8 (6 sp2 tertiary C), 123.1 and 134.3 (4CH, Ar),
168.3 (2C@O, Ar), 183.3 (C@O), 202.4 (C@S). MS (EI,
70 eV), m/z (%): 468 (M+, 5), 436 (10), 308 (21).
2-(3-Oxo-5-thioxo-3H,4H,5H-bis[1,2]dithiolo[3,4-b:40,30-
e][1,4]thiazin-4-yl)ethyl formate 1h, yield 78%. Red
crystals, mp 188–189 °C. Anal. Calcd for C9H5NO3S6:
C, 29.41; H, 1.37; N, 3.81. Found: C, 29.62; H, 1.52; N,
3.87. 1H NMR (250 MHz, Py-d5) d: 4.54 (2H, t, J 4.6,
CH2), 4.60 (2H, br s, CH2), 8.38 (s, 1H, C(O)H). 13C
NMR(75.5 MHz, Py-d5) d: 45.8 and 63.0 (2CH2), 137.1,
148.0, 150.3 and 158.4 (4 sp2 tertiary C), 161.4 (C(O)H),
183.4 (C@O), 202.7 (C@S). MS (EI, 70 eV), m/z (%): 367
(M+, 16), 308 (10), 295 (13).
4-(2-Azidoethyl)-3H,4H,5H-bis[1,2]dithiolo[3,4-b:40,30-e]-
[1,4]thiazine-3,5-dione 5c, yield 58%. Yellow crystals, mp
166–168 °C. Anal. Calcd for C8H4N4O2S5: C, 27.57; H,
1.16; N, 16.08. Found: C, 27.39; H, 1.08; N, 15.97. 1H
NMR (250 MHz, Py-d5) d: 3.64 (2H, t, J 5.3, CH2), 4.20
(2H, t, J 5.3, CH2). 13C NMR (75.5 MHz, Py-d5) d: 43.7
and 49.7 (2CH2), 134.7 and 147.0 (4 sp2 tertiary C), 181.6
(2C@O). MS (EI, 70 eV), m/z (%): 348 (M+, 11), 292 (19).
3-(3,5-Dioxo-3H,4H,5H-bis[1,2]dithiolo[3,4-b:40,30-e][1,4]-
thiazin-4-yl)propanenitrile 5f, yield 49%. Yellow crystals,
mp 184–186 °C. Anal. Calcd for C9H4N2O2S5: C, 32.51;
H, 1.21; N, 8.43. Found: C, 32.62; H, 1.29; N, 8.62. 1H
NMR (250 MHz, Py-d5) d: 2.99 (2H, t, J 6.4, CH2), 4.32
(2H, t, J 6.4, CH2). 13C NMR (75.5 MHz, Py-d5) d: 17.6
and 43.0 (2CH2), 118.7 (CN), 135.3 and 154.2 (4 sp2
tertiary C), 183.2 (2C@O). MS (EI, 70 eV), m/z (%): 332
(M+, 48), 292 (100).
4-(2-Azidoethyl)-5-thioxo-3H,4H,5H-bis[1,2]dithiolo[3,4-
b:40,30-e][1,4]thiazin-3-one 1c, yield 65%. Red crystals,
mp 187–189 °C. Anal. Calcd for C8H4N4OS6: C, 26.36; H,
1.11; N, 15.37. Found: C, 26.09; H, 1.19; N, 15.17.
C8H4N4OS6 requires M, 363.8709. Found M+, 363.8709.
1H NMR (250 MHz, Py-d5) d: 3.29 (2H, t, J 5.3, CH2),
4.09 (2H, t, J 5.3, CH2). 13C NMR (75.5 MHz, Py-d5) d:
45.7 and 51.3 (2CH2), 136.8, 147.8, 150.3 and 158.3 (4 sp2
tertiary C), 183.4 (C@O), 202.6 (C@S). MS (EI, 70 eV),
m/z (%): 364 (M+, 19), 308 (30), 262 (59).
13. Barriga, S.; Konstantinova, L. S.; Marcos, C. F.; Rakitin,
O. A.; Rees, C. W.; Torroba, T.; White, A. J. P.; Williams,
D. J. J. Chem. Soc., Perkin Trans. 1 1999, 2237–2241.
14. (a) Barriga, S.; Fuertes, P.; Marcos, C. F.; Torroba, T.
´
J. Org. Chem. 2004, 69, 3672–3682; (b) Garcıa-Valverde,
M.; Pascual, R.; Torroba, T. Org. Lett. 2003, 5, 929–932.
15. Amelichev, S. A.; Konstantinova, L. S.; Lyssenko, K. A.;
Rakitin, O. A.; Rees, C. W. Org. Biomol. Chem. 2005, 3,
3496–3501.
4-[2-(Phenylthio)ethyl]-5-thioxo-3H,4H,5H-bis[1,2]di-
thiolo[3,4-b:40,30-e][1,4]thiazin-3-one 1e, yield 54%. Red