Synthesis of alkyl bis(dimethylamino)methylenecarbamodithioates from 1,1,3,3-tetramethylguanidine, CS2 and oxiranes

Article abstract of DOI:10.1016/j.cclet.2012.04.016

An efficient synthesis of alkyl bis(dimethylamino) methylenecarbamodithioates via a one-pot reaction between 1,1,3,3- tetramethylguanidine, carbon disulfide and substituted oxiranes, in good yields, is described.

Full text of DOI:10.1016/j.cclet.2012.04.016

Available online at www.sciencedirect.com
Chinese Chemical Letters 23 (2012) 699–702
www.elsevier.com/locate/cclet
Synthesis of alkyl bis(dimethylamino)methylenecarbamodithioates
from 1,1,3,3-tetramethylguanidine, CS2 and oxiranes
Sima Yavari a, Samira Nasiri-Gheidari b, Avat (Arman) Taherpour a, Issa Yavari b,
*
a Department of Chemistry, Arak Branch, Islamic Azad University, Arak, Iran
b Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran
Received 27 February 2012
Available online 10 May 2012
Abstract
An efficient synthesis of alkyl bis(dimethylamino)methylenecarbamodithioates via a one-pot reaction between 1,1,3,3-
tetramethylguanidine, carbon disulfide and substituted oxiranes, in good yields, is described.
# 2012 Issa Yavari. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Carbamodithioate; Oxirane; Tetramethylguanidine; Carbon disulfide; One-pot reaction; Solvent free
Carbon–sulfur bond formation is a fundamental approach to introduce sulfur into organic compounds [1–3]. Sulfur
is present in many molecules that are of biological, pharmaceutical, and material interest [4]. Organic
dithiocarbamates are important in medicinal [5] and agricultural chemistry [6]. These compounds are used in the
rubber industry as vulcanization accelerators [7], in controlled radical polymerization techniques [8], and recently, in
the synthesis of ionic liquids [9].
Because of the strain induced by the presence of a three-membered ring [10], epoxides are significantly more
reactive than other cyclic ethers. Synthetic procedures for opening epoxide ring can be based on nucleophilic or acid-
mediated ring opening [11]. Suitable epoxide opening catalysts include Lewis acids, Lewis bases, Brønsted acids, and
porphyrin complexes.
1. Experimental
Compounds 1, 2, and CS2 were obtained from Merck and were used without further purification. M.p.:
Electrothermal-9100 apparatus. IR spectra (KBr): Shimadzu IR-460 spectrometer; in cmÀ1. 1H and 13C NMR spectra:
Bruker DRX-500 Avance instrument; in CDCl3 at 500.1 and 125.7 MHz, resp.; d in ppm, J in Hz. MS: Finnigan-MAT-
8430 mass spectrometer, at 70 eV; in m/z (rel. %). Elemental analyses (C, H, N): Heraeus CHN-O-Rapid analyzer.
* Corresponding author.
E-mail address: yavarisa@modares.ac.ir (I. Yavari).
1001-8417/$ – see front matter # 2012 Issa Yavari. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
http://dx.doi.org/10.1016/j.cclet.2012.04.016

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S. Yavari et al. / Chinese Chemical Letters 23 (2012) 699–702
1.1. General procedure
A mixture of 1 (0.23 g, 2 mmol) and CS2 (0.304 g, 4 mmol) was stirred for 10 min. Then, the epoxide 3 (2 mmol)
was added and the reaction mixture was stirred at room temperature. After completion of the reaction (1–2 h,
monitored by TLC), the residue was purified by column chromatography (SiO2; hexane/AcOEt 9:1) to afford pure 4.
1.1.1. 2-Hydroxypropyl bis(dimethylamino)methylenecarbamodithioate (4a)
Pale yellow oil; yield: 0.22 g (87%). Anal. Calcd. for C9H19N3OS2 (249.4): C, 43.34; H, 7.68; N, 16.85; S, 25.71%.
Found: C, 43.03; H, 7.60; N, 17.05; S, 25.53%. IR (KBr, cmÀ1): 3371, 2916, 1597, 1397, 1282, 1170, 1022; 1H NMR
(500 MHz, CDCl3): d 1.01 (d, 3H, 3J = 6.4 Hz), 2.83 (s, 12H, 2Â NMe2), 3.27–3.32 (m, 2H, SCH2), 3.80–3.81 (m, 1H,
CHOH), 3.92 (br s, 1H, OH); 13C NMR (125 MHz, CDCl3): d 22.5 (Me), 40.5 (2Â NMe2), 43.9 (SCH2), 67.6 (CHOH),
168.3 (C N), 199.7 (C S). MS (EI, 70 eV): m/z (%) 251 (M++2, 1), 250 (M++1, 1), 249 (M+, 10), 232 (20), 205 (22),
190 (42), 158 (100), 114 (50), 91 (64), 59 (23).
1.1.2. 2,3-Dihydroxypropyl bis(dimethylamino)methylenecarbamodithioate (4b)
Pale yellow oil; yield: 0.25 g (95%). Anal. Calcd. for C9H19N3O2S2 (265.4): C, 40.73; H, 7.22; N, 15.83; S, 24.16%.
Found: C, 40.56; H, 7.10; N, 15.68; S, 24.33%. IR (KBr, cmÀ1): 3369, 2911, 1592, 1393, 1283, 1174, 1027; 1H NMR
(500 MHz, CDCl3): d 2.98 (s, 12H, 2Â NMe2), 3.18–3.20 (m, 2H, SCH2), 3.56 (dd, 2H, DnAB = 11.2 Hz,
3
3
3JAB = 11.0 Hz, JAX = 5.7 Hz, JBX = 4.5 Hz, CH2), 3.80–3.81 (m, 1H, CHOH), 4.47 (br s, 1H, OH); 13C NMR
(125 MHz, CDCl3): d 38.7 (2Â NMe2), 39.6 (SCH2), 64.6 (OCH2), 71.5 (CHOH), 168.6 (C N), 199.8 (C S). MS (EI,
70 eV): m/z (%) 267 (M++2, 1), 266 (M++1, 1), 265 (M+, 10), 221 (11), 204 (10), 158 (100), 114 (83), 61 (35).
1.1.3. 2-Hydroxybutyl bis(dimethylamino)methylenecarbamodithioate (4c)
Pale yellow oil; yield: 0.27 g (93%). Anal. Calcd. for C10H21N3OS2 (263.42): C, 45.59; H, 8.04; N, 15.95; S,
24.34%. Found: C, 45.75; H, 8.12; N, 15.86; S, 24.53%. IR (KBr, cmÀ1): 3368, 2917, 1596, 1396, 1284, 1170, 1020;
1H NMR (500 MHz, CDCl3): d 0.84 (t, 3H, 3J = 7.4 Hz, Me), 1.43–1.46 (m, 2H, CH2), 2.90 (s, 12H, 2NMe2), 2.93–
2.95 (m, 1H, CH), 2.96–2.99 (m, 1H, CH), 3.04–3.08 (m, 1H, CH), 3.81 (br s, 1H, OH); 13C NMR (125 MHz, CDCl3):
d 9.9 (Me), 29.5 (CH2), 40.6 (2Â NMe2), 42.3 (SCH2), 73.2 (CHOH), 168.5 (C N), 200.9 (C S). MS (EI, 70 eV): m/z
(%) 265 (M++2, 1), 264 (M++1, 1), 263 (M+, 10), 219 (13), 204 (11), 234 (15), 191 (34), 158 (100), 59 (13).
1.1.4. 2-Hydroxy-3-phenoxypropyl bis(dimethylamino)methylenecarbamodithioate (4d)
Pale yellow oil; yield: 0.30 g (87%). Anal. Calcd. for C15H23N3O2S2 (341.49): C, 52.76; H, 6.79; N, 12.30; S,
18.78%. Found: C, 52.47; H, 6.67; N, 12.17; S, 18.62%. IR (KBr, cmÀ1): 3374, 2918, 1599, 1392, 1281, 1170, 1020;
1H NMR (500 MHz, CDCl3): d 3.04 (s, 12H, 2Â NMe2), 3.34 (dd, 2H, 2J = 5.0 Hz, 3J = 5.8 Hz, CH2), 4.01 (dd, 2H,
2J = 5.7 Hz, 3J = 4.9 Hz, OCH2), 4.28 (m, 1H, OCH), 4.61 (br s, 1H, OH), 5.23–5.32 (m, 1H, CHOH), 6.89–6.91 (m,
3
3H, 3CH), 7.26 (t, 2H, J = 7.8 Hz, 2Â CH); 13C NMR (125 MHz, CDCl3): d 41.4 (2NMe2), 42.3 (SCH2), 71.2
(OCH2), 71.4 (CHOH), 115.4 (2 CH), 121.7 (CH), 130.2 (CH), 159.4 (C), 169.3 (C N), 202.4 (C S). MS (EI, 70 eV):
m/z (%) 343 (M++2, 1), 342 (M++1, 1), 341 (M+, 10), 297 (11), 227 (10), 184 (44), 158 (100), 115 (55), 71 (80).
1.1.5. 2-Hydroxycyclohexyl bis(dimethylamino)methylenecarbamodithioate (4e)
Pale yellow oil; yield: 0.26 g (92%). Anal. Calcd. for C12H23N3OS2 (289.46): C, 49.79; H, 8.01; N, 14.52; S,
22.16%. Found: C, 49.43; H, 8.13; N, 14.66; S, 22.01%. IR (KBr, cmÀ1): 3360, 2913, 1599, 1394, 1281, 1178, 1021;
1H NMR (500 MHz, CDCl3): d 1.53–1.58 (m, 4H, 2Â CH2), 1.89–1.95 (m, 4H, 2CH2), 2.86 (s, 12H, 2NMe2), 3.28–
3.31 (m, 2H, 2Â CH), 4.56 (1H, br s, OH); 13C NMR (125 MHz, CDCl3): d 23.9 (CH2), 25.9 (CH2), 31.0 (CH2), 35.5
(CH2), 40.6 (2NMe2), 55.1 (CH), 75.1 (CHOH), 168.3 (C N), 201.1 (C S). MS (EI, 70 eV): m/z (%) 291 (M++2, 1),
290 (M++1, 1), 289 (M+, 10), 272 (10), 245 (10), 195 (30), 175 (32), 158 (100), 131 (43).
1.1.6. 3-(Allyloxy)-2-hydroxypropyl bis(dimethylamino)methylenecarbamodithioate (4f)
Pale yellow oil; yield: 0.27 g (93%). Anal. Calcd. for C12H23N3O2S2 (305.46): C, 47.18; H, 7.59; N, 13.76; S,
20.99%. Found: C, 47.45; H, 7.42; N, 13.53; S, 21.17%. IR (KBr, cmÀ1): 3368, 2917, 1596, 1396, 1284, 1170, 1020;
1H NMR (500 MHz, CDCl3): d 2.87 (s, 12H, 2Â NMe2), 2.94 (dd, 1H, 2J = 12.1 Hz, 3J = 6.1 Hz, CH2), 3.18 (dd, 1H,
2J = 12.1 Hz, 3J = 7.1 Hz, CH2), 3.40 (dd, 1H, 2J = 9.1 Hz, 3J = 7.1 Hz, CH2), 3.65 (dd, 1H, 3J = 9.1 Hz, 3J = 4.8 Hz,

S. Yavari et al. / Chinese Chemical Letters 23 (2012) 699–702
701
CH2), 4.04–4.06 (m, 2H, CH2), 4.60 (br s, 1H, OH), 4.66–4.80 (m, 1H, CHOH), 5.12–5.20 (m, 1H, CH), 5.80–5.85 (m,
1H, CH), 6.06–6.08 (m, 1H, CH). 13C NMR (125 MHz, CDCl3): d 40.8 (2NMe2), 41.8 (SCH2), 64.8 (CHOH), 69.2
(CH2O), 73.3 (CHOH), 116.2 (CH2), 135.3 (CH), 167.6 (C N), 196.4 (C S). MS (EI, 70 eV): m/z (%) 307 (M++2, 1),
306 (M++1, 1), 305 (M+, 11), 272 (10), 245 (10), 195 (30), 175 (32), 158 (100), 131 (43).
1.1.7. 2-Hydroxy-3-isopropoxypropyl bis(dimethylamino)methylenecarbamodithioate (4g)
Pale yellow oil; yield: 0.27 g (88%). Anal. Calcd. for C12H25N3O2S2 (307.48): C, 46.87; H, 8.20; N, 13.67; S,
20.86%. Found: C, 46.55; H, 8.29; N, 13.78; S, 20.63%. IR (KBr, cmÀ1): 3364, 2914, 1593, 1391, 1283, 1170, 1022;
1H NMR (500 MHz, CDCl3): d 1.03 (d, 3H, 3JAB = 6.8 Hz, Me), 1.10 (d, 3H, 3JAB = 6.8 Hz, Me), 2.94 (s, 12H, 2Â
NMe2), 3.13 [2H, (AB)X System, DnAB = 5.0 Hz, 3JAB = 15.0 Hz, 3JAX = 4.1 Hz, 3JBX = 3.0 Hz, SCH2), 3.38 (dd, 2H,
3
3
3
3
DnAB = 8.5 Hz, JAB = 9.5 Hz, JAX = 6.1 Hz, JBX = 5.7 Hz, OCH2), 3.51 (q, 1H, JAB = 6.8 Hz, CH), 3.92 (q, 1H,
3JAB = 4.5 and 15.0 Hz, CH), 4.78–4.82 (m, 1H, CHOH), 4.92 (br s, 1H, OH); 13C NMR (125 MHz, CDCl3): d 22.0
(Me), 22.6 (Me), 39.3 (SCH2), 40.6 (2NMe2), 70.8 (OCH2), 70.9 (CH), 72.1 (CH), 168.5 (C N), 201.1 (C S). MS (EI,
70 eV): m/z (%) 309 (M++2, 1), 308 (M++1, 1), 307 (M+, 10), 263 (40), 204 (20), 190 (10), 158 (100), 149 (45), 103
(10), 59 (42).
1.1.8. 2-Hydroxy-2-phenylethyl bis(dimethylamino)methylenecarbamodithioate (4h)
Pale yellow oil; yield: 0.29 g (96%). Anal. Calcd. for C14H21N3OS2 (311.47): C, 53.99; H, 6.80; N, 13.49; S,
20.59%. Found: C, 53.63; H, 6.87; N, 13.21; S, 20.40%. IR (KBr, cmÀ1): 3377, 2910, 1593, 1392, 1281, 1178, 1028;
1H NMR (500 MHz, CDCl3): d 2.88 (s, 12H, 2Â NMe2), 3.11 (dd, 1H, 2J = 7.5 Hz, 3J = 13.2 Hz, SCH2), 3.28 (dd,1H,
2J = 4.7 Hz, 3J = 13.2 Hz, SCH2), 4.69–4.73 (m, 1H, CHOH), 5.52 (d, 1H, 3J = 4.7 Hz, OH), 7.21 (t, 1H, 3J = 6.9 Hz,
CH), 7.28–7.34 (m, 4H, 4Â CH); 13C NMR (125 MHz, CDCl3): d 40.3 (2NMe2), 44.3 (SCH2), 72.3 (CHOH), 126.5
(2CH), 127.4 (CH), 128.4 (2CH), 145.3 (C), 168.4 (C N), 196.9 (C S). MS (EI, 70 eV): m/z (%) 313 (M++2, 1), 312
(M++1, 1), 311 (M+, 10), 267 (16), 204 (12), 197 (78), 158 (100), 107 (45), 77 (35).
2. Results and discussion
As part of our study on the development of new routes to organosulfur compounds [12–15], we now report the
results of our studies involving the reaction of the intermediates derived from 1,1,3,3-tetramethylguanidine (1) and
CS2 with substituted oxiranes 3, which constitutes a synthesis of open-chain products, namely, alkyl
bis(dimethylamino)methylenecarbamodithioates 4 in good yields (Scheme 1).
The reaction proceeded smoothly at room temperature and was complete within 1–2 h. The 1H NMR spectra of the
crude products clearly indicated the formation of carbamodithioates 4. Structures of compounds 4a–h were assigned
by IR, 1H NMR, 13C NMR, and mass spectral data. For example, the 1H NMR spectrum of 4a exhibited two singlets
for the N-methyl (2.83 ppm), and hydroxy (3.92 ppm) protons together with characteristic multipletes for the CH3–
1
CH–CH2 moiety. The H-decoupled 13C NMR spectrum of 4a exhibits six signals in agreement with the proposed
structure. The mass spectrum of 4a displayed the molecular ion peak at m/z = 249. The 1H- and 13C NMR spectra of
NH
N
S
R
O
solvent free
r.t.
R'
OH
CS2
N
N
N
N
S
R
R'
1
4
2
3
3,4
R
R'
Yeild % of 4
___________________________________
a
b
c
d
e
f
H
H
H
H
Me
87
95
93
87
92
88
96
90
CH2OH
Et
CH2OPh
(CH2)4
H
H
H
CH2OCH2CH=CH2
CH2OCHMe2
Ph
g
h
Scheme 1.

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S. Yavari et al. / Chinese Chemical Letters 23 (2012) 699–702
S
S
N
SH
N
S
H
O
3
+
1
+
2
+
4
N
N
N
N
R
5
7
6
Scheme 2.
compounds 4b–h are similar to those of 4a except for the alkyl and aryl groups, which show, in each case,
characteristic peaks in appropriate regions of the spectra.
Mechanistically, the reaction may proceed via the initial formation of (bis(dimethylamino)methylene)-
carbamodithioic acid 5, generated from tetramethylguanidine and CS2, followed by trapping with substituted
oxiranes (3) to give the intermediates 6 and 7 (Scheme 2). Nucleophilic attack of the carbamodithioate ion (6) on the
protonated epoxide 7 leads to product 4.
In conclusion, we have described a facile synthesis of alkyl bis(dimethylamino)methylenecarbamodithioates by
one pot reaction of tetramethylguanidine, CS2, and substituted oxiranes. The present method may be considered as a
practical route for the synthesis of carbamodithioates containing a tetramethylguanidine moiety.
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