Activated nitriles with ammonium benzyldithiocarbamate, synthesis of thietane derivatives

Article abstract of DOI:10.1080/10426500802080980

4-Aryl-2-iminothietane-3-carbonitriles 3 were obtained in a moderate yield via the reaction of substituted arylidene malononitriles with ammonium benzyldithio-carbamate. The reaction of 3a with hydrazine hydrate, ethyl carbazate, phenylisothiocyanate, and carbon disulphide have been investigated.

Full text of DOI:10.1080/10426500802080980

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Activated Nitriles
with Ammonium
Benzyldithiocarbamate,
Synthesis of Thietane
Derivatives
M. R. Mahmoud a , H. M. F. Madkour a , E. A. El-
Bordany a & E. A. Soliman a
a Chemistry Department, Faculty of Science , Ain
Shams University , Cairo , Egypt
Published online: 19 Dec 2008.
To cite this article: M. R. Mahmoud , H. M. F. Madkour , E. A. El-Bordany & E. A.
Soliman (2008) Activated Nitriles with Ammonium Benzyldithiocarbamate, Synthesis
of Thietane Derivatives, Phosphorus, Sulfur, and Silicon and the Related Elements,
184:1, 156-163, DOI: 10.1080/10426500802080980
To link to this article: http://dx.doi.org/10.1080/10426500802080980
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Phosphorus, Sulfur, and Silicon, 184:156–163, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802080980
Activated Nitriles with Ammonium
Benzyldithiocarbamate, Synthesis of Thietane Derivatives
M. R. Mahmoud, H. M. F. Madkour, E. A. El-Bordany, and
E. A. Soliman
Chemistry Department, Faculty of Science, Ain Shams University,
Cairo, Egypt
4-Aryl-2-iminothietane-3-carbonitriles 3 were obtained in a moderate yield via
the reaction of substituted arylidene malononitriles with ammonium benzyldithio-
carbamate. The reaction of 3a with hydrazine hydrate, ethyl carbazate, phenylisoth-
iocyanate, and carbon disulphide have been investigated.
Keywords Activated nitriles; ammonium benzyldithiocarbamate; pyrimidine; 1,3-
thiazine derivatives; thietane
INTRODUCTION
Thietanes have received somewhat less attention than their synthet-
ically five- or six-membered heterocyclic rings. Thus, while there are
a variety of syntheses of thietanes with particular substitution pat-
terns, there is no simple and completely general method for prepar-
ing thietanes of a wide range of ring substitution patterns. Thietanes
have been considered as odorants for natural gas.1 Other thietane
derivatives with physiological activity are useful as anti-inflammatory
agents,2 sedatives,3 and insecticides.4 Furthermore, thietanes may
be involved as intermediates in the photochemical cross linking of
4-thiouridine and cytidine units in bacterial transfer-RNA5 and
patented as a stabilizer for polyvinyl chloride.6
In conjunction with our program that aims to explore the synthetic
potential of activated nitriles and their derivatives,7−16 we report here
on the reaction of substituted arylidene malononitrile 1 with ammo-
nium benzyldithiocarbamate 2. The reaction of a 1:1 mixture of 1
and 2 in absolute ethanol afforded a colored solid for which the two
Received 8 January 2008; accepted 25 February 2008.
Address correspondence to M. R. Mahmoud, Chemistry Department, Faculty of Sci-
ence, Ain Shams University, Cairo, Egypt. E-mail: mrefaee2000@yahoo.com
156

Activated Nitriles with Ammonium Benzyldithiocarbamate
157
NH
NH2
CN
S
S
S
H
CN
CN
Ar
Ar
CN
+
(3)
H N
S
N
Ph
4
Ar
H
S
S
(1)
(2)
a, Ar = -C6H2(OMe)3 3:4:5
b, Ar = -C6H4-OMe-4
c, Ar= -C6H4-Cl-4
S
N
Ph
S
N
Ph
H
CN
Ar
NH
Ar
CN
CN
(4)
(5)
SCHEME 1
theoretically possible structures 4 and 5 were eliminated based on mi-
croanalytical and spectroscopic data. These data can only be intelligibly
interpreted in terms of structure 3 (Scheme 1).
The structure of 3 is substantiated from microanalytical data and
was confirmed by IR, 1H-NMR, 13C-NMR, and mass spectroscopy
(c.f. Exp.).
Formation of 3 may be rationalized in terms of the route shown
in Scheme 2. However, independent chemical proof for compound 3
seemed necessary. Thus, the reaction of 3a with hydrazine hydrate,
ethyl carbazate, phenylisothiocyanate, and carbon disulfide in ethano-
lic potassium hydroxide solution were also investigated (Scheme 3).
S
S
H
N
S
S
Ph
S
N
Ph
H4N
H
S
N
Ph
Michael
addition
(2)
N
C
N
Ar
Ar
NH
CN
Michael adduct
(not isolated)
CN
-
Ar
CN
(1)
Ph
N
C
S
NH2
NH
CN
S
S
Ar
CN
Ar
(3)
SCHEME 2

158
M. R. Mahmoud et al.
O
Ar
H
H
N2H4.H2O
EtOH
H
N
Ar
NHCO2Et
Ar
N
Ar
N
(7)
N2H4.H2O
(6)
H
NH2NHCO2Et
EtOH/
EtOH/
NH2
CN
S
H
Ar
(3)
Ph-N=C=S
S
CS2/KOH
Pyridine
EtOH
S
Ph
HN
S
HN
S
NH
Ar
S
CN
H
Ar
(8)
(9)
SCHEME 3
Treatment of 3a with hydrazine hydrate in boiling ethanol af-
forded the sulfur free compound which was identified to be the azine
derivative 6. The structure of 6 was confirmed by comparison (m.p.,
mixed m.p., IR, and TLC) with an authentic sample obtained from
the reaction of 3,4,5-trimethoxybenzaldehyde with hydrazine hydrate
in ethanol with 2:1 molar ratio. In a typical procedure, an equimo-
lar amount (1:1) of compound 3a and ethyl carbazate were refluxed
in ethanol for 3 h, and removal of the solvent followed by tritu-
ration with methanol left a solid product, identified to be the dia-
zoester 7. Conversion of 3 to 6 and 7 could be visualized as shown
in Scheme 4. When compound 3a was refluxed with phenylisothio-
cyanate in boiling pyridine, an insoluble product was isolated and
identified to be 3-phenyl-2,4-dithioxo-6-(3,4,5-trimethoxyphenyl)-1,2,3,

Activated Nitriles with Ammonium Benzyldithiocarbamate
159
NHR
NH2NHR
NH
HN
S
S
-H2S
H2N-NHR
NH
HS
NH
R= H, CO2Et
Ar
CN
Ar
CN
Ar
(3a)
NHR
N
H
N
H
CN
H
-
NHR
(7), R= CO2Et
CN
(3a)
N
Ar
Ar
N
(R= H)
Ar
N
(6)
Ar
CN
H
SCHEME 4
4-tetrahydropyrimidine-5-carbonitrile 8. The assigned structure 8 is
deduced from analytical data and confirmed from the spectroscopic
analysis (c.f. Exp.). Refluxing 3a with carbon disulfide in ethanolic KOH
solution affords the thermodynamically stable product 2,4-dithioxo-
6-imino-5-(3,4,5-trimehoxybenzyl-idine)3H-1,3-thiazine 9. The struc-
ture features of 9 were elucidated from the spectroscopic analysis
(Scheme 3). Conversion of 3 to 9 could be explained as shown in
Scheme 5.
S
C
NH2
NH
CN
S
S
S
Ar
CN
H
Ar
H
N
(3)
H
N
S
S
S
N
S
S
S
cyclization
SH
H
S
S
Ar
C
N
Ar
Ar
NH
NH
(9)
SCHEME 5

160
M. R. Mahmoud et al.
EXPERIMENTAL
All melting points are uncorrected. The infrared spectra are recorded
on FTIR Maltson (infinity series) spectrometers as KBr discs. The 1H-
NMR spectra were measured on Varian Gemini 200 MHz instrument
with chemical shift (δ) expressed in ppm downfield from TMS. Mass
spectra were recorded on Shimaduzu GC-MS, QP 1000 EX instrument
operating at 70 eV. TLC was run using TLC aluminum sheets silica gel
F254 (Merck).
General Method for Synthesis of 4-Aryl-2-imino-thietane-
3-carbonitriles (3a–c)
A mixture of ammonium benzyldithiocarbamate (2 g, 10 mmol) and
arylidene malononitrile (10 mmol) was refluxed in 30 mL ethanol for
1 h until there was no more substrate (TLC). The solid deposited on hot
was filtered off, dried, and recrystallized from suitable solvent to give
compounds 3a–c.
2-Imino-4-(3,4,5-trimethoxyphenyl) thietane-3-carbonitrile (3a)
Recrystallized from benzene as orange crystals, m.p. 198–200◦C,
yield 50%. IR (KBr): 3393, 3262, 3153 cm−1 (NH2), 2978, 2942, 2836
cm−1 (C-H), 2208 cm−1 (C≡N), 1636 cm−1 (C N). 1H-NMR (DMSO-d6,
δ ppm) 10.12 (s, 1H), 9.6 (s, 1H), 8.1 (s, 1H), 7.4 (s, 2H), 3.9 (s, 6H), 3.8
(s, 3H).13C-NMR (DMSO-d6) 159.7 (C2), 60.2 (C3), 115.1 (C≡N), 42.2
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
(C4), 134.8 (C1 ), 108.3 (C2 , C6 ), 153 (C3 , C5 ), 136.2 (C4 ), 56.3, 58.4,
55.3 (3OMe). EI-MS m/z (%): 278 (100) [M+.], 246 (78.2), 219 (16.2),
204 (20.7), 188 (10.7). Anal. Calcd. for C13H14N2O3S (278): C, 56.11; H,
5.03; N, 10.07; S, 11.52. Found: C, 55.92; H, 4.83; N, 9.66; S, 11.08.
2-Imino-4-(4-methoxyphenyl) thietane-3-carbonitrile (3b)
Recrystallized from dioxane as yellow crystals, m.p. 210–219◦C, yield
39%. IR (KBr): 3410, 3274, 3166 cm−1 (NH2), 2918, 2900 cm−1 (C-H),
2216 cm−1 (C≡N), 1632 cm−1 (C N). 1H-NMR (DMSO-d6, δ ppm) 9.6 (s,
1H), 9.1 (s, 1H), 7.8 (s, 4H), 6.8 (s, 1H), 3.76 (s, 3H). 13C-NꢀMR (DMSO-
ꢀ
ꢀ
d6)ꢀ161.7 (C2), 59.7 ꢀ(C3), 40.1 (C4), 133.3 (C1 ), 128.3 (C2 , C6 ), 115.6
ꢀ
(C3 , C5 ), 159.7 (C4 ), 55.2 (OMe), 114.7 (C≡N). EI-MS m/z (%): 218
(78.7) [M+.], 203 (100) [M – CH3]. Anal. Calcd. for C11H10N2OS (218):
C, 60.55; H, 4.59; N, 12.84; S, 14.68. Found: C, 60.08; H, 4.33; N, 12.64;
S, 14.57.
4-(4-Chlorophenyl)-2-imino-thietane-3-carbonitrile (3c)
Recrystallized from benzene as yellow crystals, m.p. 230–232◦C,
yield 53%. IR (KBr): 3402, 3281, 3160 cm−1 (NH2), 2922, 2900,

Activated Nitriles with Ammonium Benzyldithiocarbamate
161
2870 cm−1 (C-H), 2208 cm−1 (C≡N), 1642 cm−1 (C N). 1H-NMR
(DMSO-d6, δ ppm) 9.8 (s, 1H), 8.9 (s, 1H), 7.3 (m, 4H), 6.3 (s, 1H).
EI-MS m/z (%): 223 (100), 224 (5.7) [M + 1], 225 (32) [M + 2]. Anal.
Calcd. for C10H7ClN2S (222.5): C, 53.93; H, 3.15; N, 12.58; S, 14.38; Cl,
15.95. Found: C, 54.31; H, 3.36; N, 11.99; S, 14.72; Cl, 16.21.
Action of hydrazine hydrate on 3a: Formation of the azine 6
A mixture of 3a (1.3 g, 3 mmol) and hydrazine hydrate (1 g, 30 mmol)
was refluxed in 20 mL ethanol for 1 h (TLC). Evaporation of excess
ethanol left a dark brown solid which recrystallized from ethanol to
give the azine 6 as dark brown crystals, m.p. 188–190◦C, yield 33%.
IR (KBr): 2910 cm−1 (C-H), 1627 cm−1 (C N). 1H-NMR (DMSO-d6,
δ ppm) 8.1 (s, 2H, N CH), 6.8 (s, 4Harom.), 3.9 (s, 12H, 4OMe), 3.8 (s,
6H, 2OMe). EI-MS m/z (%): 388 (100) [M+], 194 (31.4), 167 (12.7). Anal.
Calcd. for C20H24N2O6 (388): C, 61.85; H, 6.18; N, 7.22. Found: C, 62.09;
H, 5.86; N, 7.43.
Authentic sample 6
To a solution of 3,4,5-trimethoxybenzaldehyde (0.39 g, 2 mmol) in
ethanol (10 mL), hydrazine hydrate (0.5 mL) was added dropwise with
stirring at room temperature for 0.5 h. The solid deposited was collected
by filtration, dried, and recrystallized from ethanol.
Reaction of 3a with ethyl carbazate: Formation of ethyl-2-
(3,4,5-trimethoxybenzyl-idine) hydrazine carboxylate 7
A mixture of 3a (2.78 g, 10 mmol) and ethyl carbazate (1.04 g,
10 mmol) was refluxed in 50 mL ethanol for 4 h (TLC). The reaction
mixture was concentrated, left to cool and the solid deposited was fil-
tered off and recrystallized from ethanol to give the diazoester 7 as pale
yellow crystals, m.p. 140–142◦C, yield 45%. IR (KBr): 3268 cm−1 (NH),
1
1719 cm−1 (C O). H-NMR (CDCl3, δ ppm) 8.7 (s, 1H), 8.2 (s, 1H), 7.2
(s, 2Harom.), 4.1 (q, 2H, J = 8.2 Hz), 1.59 (t, 3H, J = 6.1 Hz).13C-NMR
(CDCl3) 14.1 (Me), 59.2 (CH2), 156.2 (CO), 144.8 (CH N), 130.1, 108.6,
154.6, 139.6 (Carom.), 55.1, 59.3, 56.1 (3OMe). EI-MS m/z (%): 282 (76.5)
[M+.], 193 (100, M-EtOH, HN C O), 192 (87.68), 181 (40.6), 91 (30.3),
65 (23.7). Anal. Calcd. for C13H18N2O5 (282): C, 55.32; H, 6.38; N, 9.93.
Found: C, 55.14; H, 6.36; N, 10.16.
Formation of 3-phenyl-2,4-dithioxo-6-(3,4,5-trimethoxy-
phenyl)-1,2,3,4-tetrahydro-pyrimidine-5-carbonitrile 8
To a solution of 3a (2.78 g, 10 mmol) in 20 mL pyridine, phenylisoth-
iocyanate (2 mL, 15 mmol) was added, and the reaction mixture was

162
M. R. Mahmoud et al.
refluxed for 6 h (TLC) then left to cool and acidified with cold dilute
hydrochloric acid. The crud solid obtained was collected by suction,
washed with water, dried, and recrystallized from ethanol to give com-
pound 8 as brown powder, m.p. 230–232◦C, yield 70%. IR (KBr): νNH
centered at 3446 cm−1, νC=S at 1133 cm−1, 1634 cm−1 for νC=N. 1H-NMR
(DMSO-d6, δ ppm) 11.8 (s, 1H), 7.2-6.8 (m, 7Harom.), 3.93 (s, 6H, 2OMe),
3.84 (s, 3H, OMe). EI-MS m/z (%): 387 (43.6) [M-CN], 79 (81) for the
molecular ion peak C4H3N+. , 52 (100). Anal. Calcd. for C20H19N3O3S2
(413): C, 58.11; H, 4.60; N, 210.17; S, 15.49. Found: C, 58.71; H, 4.62; N,
9.93; S, 15.08.
2,4-Dithioxo-6-imino-5-(3,4,5-trimethoxybenzylidine)3H-1,3-
thiazine 9
A mixture of 3a (2.78 g, 10 mmol) and carbon disulfide (5 mL) in
potassium hydroxide (10%) (20 mL) was refluxed in a water bath for
6 h (TLC). The excess solvent was collected by distillation, and the reac-
tion mixture was left to cool, then acidified with cold dilute hydrochloric
acid. The deposited solid was collected by suction, washed with cold wa-
ter, dried, and recrystallized from benzene to give the thiazine deriva-
tive 9 as brown crystals, m.p. 142–144◦C, yield 38%. IR (KBr): 3394,
3207 cm−1 (NH), 2933, 2847 cm−1 (C-H), 1630 cm−1 (C N), 1339 cm−1
(C S). 1H-NMR (CDCl3, δ ppm) 8.6 (s, 1H), 8.1 (s, 1H), 6.9 (s, 1H), 6.7 (s,
2Harom.), 3.93 (s, 6H, 2OMe), 3.81 (s, 3H, OMe).13C-NMR (CDCl3) 204
(C2, C S), 198.2 (C4, C S), 122.3 (C5), 162.6 (C6, C NH), 141.3 (C5, =
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
CH), 129.1 (C1 ), 107.7 (C2 , C6 ), 157.1 (C3 , C5 ), 139.2 (C4 ), 54.9, 58.9,
55.1 (3OMe). EI-MS m/z (%): 354 (11.7) [M+.], 278 (39.8, M-CS2), 93
(100). Anal. Calcd. for C14H14N2O3S3 (354): C, 47.46; H, 3.95; N, 7.91;
S, 27.12. Found: C, 47.08; H, 4.32; N, 8.26; S, 26.83.
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