A one-pot synthesis of alkyl acylcarbamodithioates from acid chlorides, thiols, and ammonium thiocyanate

Article abstract of DOI:10.1007/s00706-009-0154-2

An efficient synthesis of alkyl acylcarbamodithioates by reaction of acid chlorides with ammonium thiocyanate in the presence of thiols is described. The unusually large values of ⁵J_FH = 12-15 Hz, observed for alkyl (2-fluorobenzoyl)

Full text of DOI:10.1007/s00706-009-0154-2

Monatsh Chem (2009) 140:1199–1204
DOI 10.1007/s00706-009-0154-2
ORIGINAL PAPER
A one-pot synthesis of alkyl acylcarbamodithioates
from acid chlorides, thiols, and ammonium thiocyanate
Issa Yavari Æ Nasir Iravani Æ S. Zahra Sayyed-Alangi Æ
Rahimeh Hajinasiri
Received: 22 October 2008 / Accepted: 19 January 2009 / Published online: 21 April 2009
Ó Springer-Verlag 2009
Abstract An efficient synthesis of alkyl acylcarbamodi-
thioates by reaction of acid chlorides with ammonium
thiocyanate in the presence of thiols is described. The
As a part of our current studies on the development of
new routes in the synthesis of organosulfur compounds
[11–14], we report an efficient one-pot method for syn-
thesis of alkyl acylcarbamodithioates.
5
unusually large values of JFH = 12–15 Hz, observed for
alkyl (2-fluorobenzoyl)carbamodithioates provide infor-
mation about Ar–C–N–H torsion in these compounds.
Results and discussion
Keywords Carbamodithioate Á Ammonium thiocyanate Á
Acid chloride Á Thiol
The reaction of acid chlorides 1 with ammonium thiocya-
nate in the presence of thiols 2 proceeds smoothly in dry
MeCN at rt to produce compounds 3 in good yields
(Scheme 1). The structures of compounds 3a–3r were
Introduction
1
deduced from their IR, H NMR, and 13C NMR spectro-
Alkyl carbamodithioates are a common class of organic
molecules with a variety of valuable biological effects,
including antibacterial activity [1], antifungal activity [2],
and the ability to chelate heavy metals [3, 4]. These esters
are bifunctional ligands which have received attention
because of their use as agrochemicals [5] and pharmaceu-
ticals [6]. Carbamodithioates have exceptionally strong
affinity towards Hg2? ions [7], and have been used for
controlled/living free-radical polymerization of methyl
acrylate under thermal condition [8]. Synthesis and in-vitro
antitumor activity of quinazolinone derivatives with
dithiocarbamate side chains have been reported [9]. Car-
bamodithioates have been used to prepare upper-rim-
substituted calix [4] arenes as selective extractants [10].
scopic data. The mass spectra of these compounds
contained molecular ion peaks at appropriate m/z values.
1
The H NMR spectrum of 3a in CDCl3 contained signals
for methylene (d = 2.86 and 3.59 ppm), methoxy
(d = 3.73 ppm), and NH (d = 10.59 ppm) protons, with
multiplets for the aromatic (d = 7.22–7.64 ppm) protons.
The 13C NMR spectrum of 3a contained 12 signals in
1
agreement with the proposed structure. The H and 13C
NMR spectra of 3b–3r are similar to those of 3a except for
the alkyl and acyl moieties, which give characteristic sig-
nals with appropriate chemical shifts.
The following mechanism (Scheme 2) may be invoked
for formation of compounds 3. Conceivably, the starting
point of the reaction is the formation of a 1:1 adduct, 4,
between 1 and ammonium thiocyanate, which undergoes
nucleophilic reaction with thiols 2 to produce 3.
I. Yavari Á N. Iravani Á S. Z. Sayyed-Alangi Á R. Hajinasiri
Chemistry Department, Science and Research Campus,
Islamic Azad University, Ponak, Tehran, Iran
Although the presence of the 19F nucleus complicates
1
both the H and 13C NMR spectra of 3a–3c, it helps in
assignment of the signals by direct and long range coupling
I. Yavari (&)
Chemistry Department, Tarbiat Modares University,
1
with H and 13C nuclei (‘‘Experimental’’ section). Of par-
ticular interest is the observation of an unusually high value
for the five-bond fluorine–proton coupling constants,
Tehran, Iran
e-mail: yavarisa@modares.ac.ir
123

1200
I. Yavari et al.
Scheme 1
O
R
O
S
dry CH3CN
rt
R'
S
R'-SH
NH4SCN
+
+
R
Cl
R
N
H
R'
R
R'
1a 2-F-C6H4
1b CMe3
1c Ph
2a CH2CH2CO2Me
2b CH2-C4H3O
3a 2-F-C6H4
3b 2-F-C6H4
3c 2-F-C6H4
3d CMe3
3e CMe3
3f CMe3
3g Ph
CH2CH2CO2Me
CH2-C4H3O
2c CH2CH2CH2-SH
CH2CH2CH2-SH
CH2CH2CO2Me
CH2-C4H3O
1d 4-NO2-C6H4
1e 4-MeO-C6H4
1f CH3-CH2
CH2CH2CH2-SH
CH2CH2CO2Me
CH2-C4H3O
3h Ph
3i Ph
CH2CH2CH2-SH
3j 4-NO2-C6H4 CH2CH2CO2Me
3k 4-NO2-C6H4 CH2-C4H3O
3l 4-NO2-C6H4 CH2CH2CH2-SH
3m 4-MeO-C6H4 CH2CH2CO2Me
3n 4-MeO-C6H4 CH2-C4H3O
3o 4-MeO-C6H4 CH2CH2CH2-SH
3p CH3-CH2
3q CH3-CH2
3r CH3-CH2
CH2CH2CO2Me
CH2-C4H3O
CH2CH2CH2-SH
Scheme 2
O
O
S
+ 2
3
NH4Cl
C
N
NH4SCN
+
R
Cl
R
4
1
5JFH = 12.2–15.1 Hz, which provides information about
Ar–C–N–H torsion (Scheme 4). It has been suggested [15]
that F–H spin coupling can operate not only through the
bonds in a molecule but also through space, if the inter-
acting fluorine and proton nuclei are in close proximity. In
compounds 3a–3c, the fluorine and the NH proton can
come into fairly close proximity in some conformations
(Scheme 3), and would be expected to have a large
through-space contribution to the coupling. The large
observed coupling may thus be explained.
Scheme 3
S
R'
H
F
N
S
O
proposed structure. The 1H and 13C NMR spectra of 5b–5f
are similar to those for 5a, except for the alkyl and acyl
moieties, which give characteristic signals with appropriate
chemical shifts.
When the reaction was carried out using one equivalent
of 1,3-dimercaptopropane (2c) and two equivalents of acid
chloride 1 in the presence of two equivalents of ammonium
thiocyanate, trimethyl bisacylcarbamodithioates 5a–5f
were obtained in good yields (Scheme 4). Compounds 5a–
5f were identified on the basis of their IR, 1H, and l3C NMR
spectral data. The 1H NMR spectrum of 5a in CDCl3
contained signals for methylene (d = 2.31 and 3.47 ppm)
and NH (d = 10.58 ppm) protons, with multiplets for the
aromatic (d = 7.19–8.18 ppm) protons. The 13C NMR
spectrum of 5a contained ten signals, in agreement with the
In conclusion, we have described a convenient route to
the synthesis of alkyl acylcarbamodithioates by reaction of
acid chlorides with ammonium thiocyanate in the pres-
ence of thiols. Trimethyl bisacylcarbamodithioates were
obtained from 1,3-dimercaptopropane and two equivalents
of 1 in the presence of ammonium thiocyanate. Unusual
5
large values of JFH = 12–15 Hz are observed for alkyl
(2-fluorobenzoyl)carbamodithioates; these provide infor-
mation about Ar–C–N–H torsion in these compounds.
123

A one-pot synthesis of alkyl acylcarbamodithioates
1201
Scheme 4
O
S
S
O
O
CH3CN
rt
+
+
SH SH
NH4SCN
R
N
S
S
N
R
R
Cl
H
H
R
R
2c
1a: 2-F-C6H4
2-F-C6H4
CMe3
Ph
5a:
5b:
5c:
5d:
CMe3
Ph
1b:
1c:
1d: 4-NO2-C6H4
4-MeO-C6H4
1f: CH3-CH2
4-NO2-C6H4
1e:
5e: 4-MeO-C6H4
5f: CH3-CH2
(CH2), 32.4 (CH2), 52.4 (MeO), 117.3 (d, 2JCF = 24.0 Hz,
These alkyl acylcarbamodithioates can be regarded as
potentially useful synthetic intermediates. The simplicity
of the present procedure makes it an interesting alternative
to other approaches.
2
CH), 119.5 (d, JCF = 20.5 Hz, C), 125.8 (d, JCF
4
=
3
3.2 Hz, CH), 132.4 (d, JCF = 9.9 Hz, CH), 136.1
3
1
(d, JCF = 9.7 Hz, CH), 160.9 (d, JCF = 249.0 z, C–F),
163.3 (d, 3JCF = 4.1 Hz, C=O), 172.4 (C=O), 203.4 (C=S)
ppm.
Experimental
(Furan-2-yl)methyl (2-fluorobenzoyl)
carbamodithioate (3b, C13H10FNO2S2)
Compounds 1 and 2 were obtained from Fluka and were
used without further purification; M.p.: Electrothermal
9100 apparatus; IR spectra: Shimadzu IR-460 spectrome-
Yellow oil; Rf: 0.74; yield: 0.46 g (78%); IR (KBr):
vꢀ = 3400 (NH), 1694 (C=O), 1152 (C=S) cm-1; EI-MS:
m/z (%) = 295 (21, M?), 228 (16), 214 (22), 192 (32),
1722 (25), 123 (100), 81 (11), 67 (38); 1H NMR: d = 4.61
1
ter; H and 13C NMR spectra: Bruker DRX-300 Avance
instrument; in CDCl3 at 300 MHz and 75 MHz; EI-MS
(70 eV): Finningan-MAT-8430 mass spectrometer. Ele-
mental analyses (C, H, and N) were performed with a
Heraeus CHN-O-Rapid analyzer. The mass spectral and
elemental analysis data were in agreement with the pro-
posed structures.
3
(s, CH2), 6.42 (d, JHH = 1.8 Hz, CH furan), 6.47 (t,
3JHH = 3.2 Hz, CH furan), 7.39–7.41 (m, CH arom), 7.43–
3
7.54 (m, CH arom), 7.55 (d, JHH = 1.3 Hz, CH furan),
7.67–7.72 (m, CH arom), 7.87–7.93 (m, CH arom), 11.48
(d, 5JHF = 14.8 Hz, NH) ppm; 13C NMR: d = 34.1 (CH2),
109.7 (CH furan), 111.1 (CH furan), 135.4 (CH furan),
2
2
117.2 (d, JCF = 24.2 Hz, CH), 119.4 (d, JCF = 19.8 Hz,
General procedure for the preparation of alkyl
acylcarbamodithioates 3
4
C), 125.9 (d, JCF = 3.4 Hz, CH), 132.6 (d, JCF
3
3
= 9.4 Hz, CH), 136.3 (d, JCF = 9.7 Hz, CH), 161.0 (d,
3
1JCF = 249.4 Hz, C–F), 163.5 (d, JCF = 3.3 Hz, C=O),
162.2 (C=O), 202.9 (C=S) ppm.
To a stirred solution of 0.15 g NH4SCN (2 mmol) in
10 cm3 MeCN were added 2 mmol acid chloride 1. The
mixture was stirred at rt for 30 min. Then, 2 mmol thiol 2
was added and the reaction mixture was stirred for 2 h at rt.
The solvent was removed under reduced pressure and
the residue was purified by column chromatography (SiO2,
n-hexane–EtOAc 3:1) to afford the pure title compounds.
3-Mercaptopropyl (2-fluorobenzoyl)carbamodithioate
(3c, C11H12FNOS3)
Yellow oil; Rf: 0.74; yield: 0.49 g (84%); IR (KBr):
vꢀ = 3391 (NH), 1688 (C=O), 1153 (C=S) cm-1; EI-MS:
m/z (%) = 289 (21, M?), 256 (12), 243 (32), 242 (31), 182
(28), 166 (34), 123 (100), 47 (60), 46 (38), 33 (22); 1H NMR:
d = 1.45 (t, 3JHH = 7.2 Hz, SH), 2.11 (qui, 3JHH = 7.1 Hz,
2-(Methoxycarbonyl)ethyl (2-fluorobenzoyl)
carbamodithioate (3a, C12H12FNO3S2)
Yellow oil; Rf: 0.61; yield: 0.50 g (83%); IR (KBr):
3
3
CH2), 2.70 (q, JHH = 7.4 Hz, CH2), 3.43 (t, JHH
7.2 Hz, CH2S), 7.19–7.27 (m, CH arom), 7.33–7.38 (m,
=
vꢀ = 3384 (NH), 1733, 1693 (C=O), 1151 (C=S) cm-1
;
EI-MS: m/z (%) = 301 (5, M?), 270 (6), 242 (22), 215
(52), 182 (25), 139 (25), 123 (100), 119 (34), 95 (60), 87
(11), 75 (38), 69 (8), 59 (22); 1H NMR: d = 2.86 (t,
3JHH = 7.2 Hz, CH2), 3.59 (t, 3JHH = 7.2 Hz, CH2S), 3.73
(s, MeO), 7.22–7.27 (m, CH arom), 7.33–7.38 (m, CH
arom), 7.59–7.64 (m, CH arom), 8.11–8.16 (m, CH arom),
CH arom), 7.59–7.66 (m, CH arom), 8.11–8.17 (m, CH
5
arom), 10.59 (d, JHF = 14.31 Hz, NH) ppm; 13C NMR:
d = 23.9 (CH2), 31.7 (CH2), 35.5 (CH2), 117.2 (d,
2
2JCF = 24.1 Hz, CH), 119.4 (d, JCF = 9.9 Hz, C), 125.9
4
(d, JCF = 3.1 Hz, CH), 132.6 (d, JCF = 9.4 Hz, CH),
3
3
1
136.3 (d, JCF = 9.7 Hz, CH), 161.0 (d, JCF = 248.1 Hz,
C–F), 163.5 (d, 3JCF = 3.4 Hz, C=O), 203.7 (C=S) ppm.
5
10.59 (d, JFH = 15 Hz, NH) ppm; 13C NMR: d = 31.9
123

1202
I. Yavari et al.
3
2-(Methoxycarbonyl)ethyl pivaloylcarbamodithioate
(3d, C10H17NO3S2)
d = 4.61 (s, CH2), 6.34 (d, JHH = 1.7 Hz, CH furan),
6.38 (t, 3JHH = 3.4 Hz, CH furan), 7.39 (d, 3JHH = 1.5 Hz,
CH furan), 7.51–7.56 (m, 2 CH arom), 7.62–7.67 (m, CH
arom), 7.89 (m, 2 CH arom), 10.08 (s, NH) ppm; 13C
NMR: d = 35.1 (CH2), 109.8 (CH furan), 111.9 (CH
furan), 128.1 (2 CH arom), 129.6 (CH arom), 133.9 (CH
furan), 143.5 (2 CH arom), 1639 (C=O), 203.1 (C=S) ppm.
Yellow oil; Rf: 0.76; yield: 0.45 g (85%); IR (KBr): vꢀ = 3405
(NH), 1707, 1686 (C=O), 1123 (C=S) cm-1; EI-MS: m/z
(%) = 263 (9, M?), 232 (6), 204 (26), 178 (42), 144 (35), 119
(25), 85 (100), 59 (23); 1H NMR: d = 1.31 (s, CMe3), 2.82 (t,
3
3JHH = 7.2 Hz, CH2), 3.52 (t, JHH = 7.2 Hz, CH2S), 3.72
(s, MeO), 9.54 (s, NH) ppm; 13C NMR: d = 27.4 (CMe3),
31.9 (CH2), 32.4 (CH2), 40.5 (CMe3), 52.36 (MeO), 172.3
(C=O), 175.6 (C=O), 204.2 (C=S) ppm.
3-Mercaptopropyl benzoylcarbamodithioate
(3i, C11H13NOS3)
Yellow oil; Rf: 0.75; yield: 0.45 g (83%); IR (KBr):
vꢀ = 3396 (NH), 1689 (C=O), 1146 (C=S) cm-1; EI-MS:
m/z (%) = 271 (8, M?), 238 (17), 225 (29), 224 (46), 166
2-(Furan-2-yl)methyl pivaloylcarbamodithioate
(3e, C11H15NO2S2)
1
Yellow oil; Rf: 0.85; yield: 0.42 g (83%); IR (KBr):
vꢀ = 3401 (NH), 1706, 1686, 1148 (C=S) cm-1; EI-MS: m/
z (%) = 257 (12, M?), 190 (6), 176 (26), 172 (39), 154
(30), 103 (29), 85 (100), 81 (40), 67 (15); 1H NMR:
d = 1.31 (s, CMe3), 4.57 (s, CH2), 6.32 (d, 3JHH = 1.6 Hz,
(25), 164 (35), 105 (100), 47 (38), 46 (19), 33 (38); H
3
NMR: d = 1.45 (t, JHH = 7.6 Hz, SH), 2.13 (qui,
3
3JHH = 7.3 Hz, CH2), 2.69 (q, JHH = 7.5 Hz, CH2),
3.46 (t, 3JHH = 7.3 Hz, CH2S), 7.51–7.56 (m, 2 CH arom),
7.67–7.69 (m, CH arom), 7.89–7.91 (m, 2 CH arom), 10.07
(s, NH) ppm; 13C NMR: d = 23.9 (CH2), 29.2 (CH2), 36.4
(CH2), 127.6 (2 CH arom), 129.3 (CH arom), 133.8 (2 CH
arom), 163.8 (C=O), 204.1 (C=S) ppm.
3
CH furan), 6.39 (t, JHH = 2.8, CH furan), 7.37 (d,
3JHH = 1.4 Hz, CH furan), 9.54 (s, NH) ppm; 13C NMR:
d = 27.7 (CMe3), 39.8 (CH2), 40.1 (CMe3), 109.7 (CH
furan), 111.2 (CH furan), 142.9 (CH furan), 175.7 (C=O),
203.5 (C=S) ppm.
2-(Methoxycarbonyl)ethyl (4-nitrobenzoyl)
carbamodithioate (3j, C12H12N2O5S2)
3-Mercaptopropyl pivaloylcarbamodithioate
(3f, C9H17NO2S3)
Yellow oil; Rf: 0.61; yield: 0.58 g (88%); IR (KBr):
vꢀ = 3364 (NH), 1713, 1690 (C=O), 1154 (C=S) cm-1; EI-
MS: m/z (%) = 328 (10, M?), 297 (23), 269 (41), 209 (32),
178 (20), 150 (100), 119 (18), 59 (31); 1H NMR: d = 2.88
Yellow oil; Rf: 0.85; yield: 0.46 g (86%); IR (KBr):
vꢀ = 3403 (NH), 1707 (C=O), 1140 (C=S) cm-1; EI-MS:
m/z (%) = 267 (9, M?), 234 (8), 221 (28), 220 (58), 160
3
(t, 3JHH = 7.1 Hz, CH2), 3.61 (t, JHH = 7.1 Hz, CH2S),
3
3.76 (s, MeO), 8.09 (d, JHH = 8.9 Hz, 2 CH arom), 8.41
1
(42), 107 (31), 85 (100), 47 (21), 46 (12), 33 (17); H
3
3
NMR: d = 1.31 (s, CMe3), 1.43 (t, JHH = 7.4 Hz, SH),
2.07 (qui, JHH = 7.1 Hz, CH2), 2.67 (q, JHH = 7.4 Hz,
(d, JHH = 8.9 Hz, 2 CH arom), 9.97 (s, NH) ppm; 13C
3
3
NMR: d = 31.9 (CH2S), 32.1 (CH2), 51.6 (MeO), 128.2 (2
CH arom), 129.5 (2 CH arom), 150.6 (C-NO2), 163.9
(C=O), 172.4 (C=O), 203.4 (C=S) ppm.
3
CH2), 3.38 (t, JHH = 7.2 Hz, CH2S), 9.54 (s, NH) ppm;
13C NMR: d = 24.2 (CH2), 27.4 (CMe3), 31.7 (CH2), 39.9
(CH2), 40.0 (CMe3), 175.6 (C=O), 204.5 (C=S) ppm.
(Furan-2-yl)methyl (4-nitrobenzoyl)carbamodithioate
(3k, C13H10N2O4S2)
2-(Methoxycarbonyl)ethyl benzoylcarbamodithioate
(3g, C12H13NO3S2)
Yellow oil; Rf: 0.77; yield: 0.55 g (86%); IR (KBr):
vꢀ = 3386 (NH), 1696 (C=O), 1147 (C=S) cm-1; EI-MS:
m/z (%) = 322 (9, M?), 255 (6), 241 (22), 219 (42), 172
(25), 150 (100), 103 (38), 81 (27), 67 (22); 1H NMR:
Yellow oil; Rf: 0.57; yield: 0.47 g (82%); IR (KBr):
vꢀ = 3386 (NH), 1734, 1695 (C=O), 1146 (C=S) cm-1; EI-
MS: m/z (%) = 283 (14, M?), 252 (18), 224 (28), 178 (43),
164 (35), 119 (23), 105 (100), 59 (19); 1H NMR: d = 2.86
3
d = 4.61 (s, CH2), 6.66 (d, JHH = 1.6 Hz, CH furan),
3
3
(t, JHH = 7.1 Hz, CH2), 3.58 (t, JHH = 7.1 Hz, CH2S),
3.71 (s, MeO), 7.51–7.55 (m, 2 CH arom), 7.61–7.64 (m,
CH arom), 7.86–7.91 (m, 2 CH arom), 10.08 (br s, NH)
ppm; 13C NMR: d = 31.9 (CH2), 32.4 (CH2), 52.4 (MeO),
128.1 (CH arom), 129.6 (CH arom), 133.9 (CH arom),
163.8 (C=O), 172.3 (C=O), 203.8 (C=S) ppm.
6.41 (t, 3JHH = 3.3 Hz, CH furan), 7.80 (d, 3JHH = 1.7 Hz,
3
CH furan), 8.07 (d, JHH = 8.5 Hz, 2 CH arom), 8.38 (d,
3JHH = 8.5 Hz, 2 CH arom), 10.00 (s, NH) ppm; 13C
NMR: d = 35.2 (CH2), 110.1 (CH furan), 111.2 (CH
furan), 124.7 (2 CH arom), 129.4 (2 CH arom), 143.2 (CH
furan), 151.2 (C-NO2), 162.1 (C=O), 202.5 (C=S) ppm.
(Furan-2-yl)methyl benzoylcarbamodithioate
(3h, C13H11NO2S2)
3-Mercaptopropyl (4-nitrobenzoyl)carbamodithioate
(3l, C11H12N2O3S3)
Yellow oil; Rf: 0.74; yield: 0.45 g (82%); IR (KBr):
vꢀ = 3380 (NH), 1694 (C=O), 1148 (C=S) cm-1; EI-MS:
m/z (%) = 277 (9, M?), 210 (13), 196 (28), 174 (47), 172
(30), 105 (100), 103 (62), 81 (19), 67 (31); 1H NMR:
Yellow oil; Rf: 0.77; yield: 0.49 g (78%); IR (KBr):
vꢀ = 3434 (NH), 1684 (C=O), 1148 (C=S) cm-1; EI-MS:
m/z (%) = 316 (8, M?), 283 (20), 270 (25), 269 (52), 209
(29), 166 (25), 150 (100), 107 (60), 47 (11), 46 (38), 33 (8);
123

A one-pot synthesis of alkyl acylcarbamodithioates
1203
3
1H NMR: d = 1.46 (t, JHH = 7.3 Hz, SH), 2.13 (qui,
MS: m/z (%) = 235 (10, M?), 204 (6), 178 (22), 176 (52),
3JHH = 7.2 Hz, CH2), 2.73 (q, JHH = 7.3 Hz, CH2), 3.46
3
1
116 (25), 119 (25), 59 (41), 57 (100), 37 (60); H NMR:
3
3
3
3
(t, JHH = 7.3 Hz, CH2S), 8.11 (d, JHH = 8.6 Hz, 2 CH
arom), 8.41 (d, 3JHH = 8.8 Hz, 2 CH arom), 10.02 (s, NH)
ppm; 13C NMR: d = 24.2 (CH2), 31.6 (CH2S), 35.9 (CH2),
124.7 (2 CH arom), 129.3 (2 CH arom), 151.2 (C-NO2),
161.9 (C=O), 203.6 (C=S) ppm.
d = 1.24 (t, JHH = 9.5 Hz, Me), 2.44 (q, JHH = 9.3 Hz,
CH2), 2.83 (t, 3JHH = 7.3 Hz, CH2), 3.52 (t,
3JHH = 7.3 Hz, CH2S), 3.73 (s, MeO), 9.47 (s, NH) ppm;
13C NMR: d = 8.9 (Me), 30.5 (CH2), 31.8 (CH2S), 32.5
(CH2), 52.4 (MeO), 170.8 (C=O), 172.3 (C=O), 203.5
(C=S) ppm.
2-(Methoxycarbonyl)ethyl (4-methoxybenzoyl)
carbamodithioate (3m, C13H15NO4S2)
(Furan-2-yl)methyl propionylcarbamodithioate
(3q, C9H11NO2S2)
Yellow oil; Rf: 0.67; yield: 0.48 g (76%); IR (KBr):
vꢀ = 3427 (NH), 1729, 1684 (C=O), 1120 (C=S) cm-1; EI-
MS: m/z (%) = 313 (10, M?), 282 (6), 254 (22), 194 (52),
178 (25), 135 (100), 119 (31), 59 (22); 1H NMR: d = 2.87
Yellow oil; Rf: 0.79; yield: 0.34 g (74%); IR (KBr):
vꢀ = 3419 (NH), 1697 (C=O), 1217 (C=S) cm-1; EI-MS:
m/z (%) = 229 (9, M?), 172 (16), 162 (32), 148 (59), 126
(42), 103 (25), 81 (53), 67 (60), 57 (100); 1H NMR:
3
3
(t, JHH = 7.2 Hz, CH2), 3.59 (t, JHH = 7.2 Hz, CH2S),
3
3.47 (s, MeO), 3.71 (s, MeO), 7.32 (d, JHH = 8.4 Hz, 2
3
3
d = 1.25 (t, JHH = 7.5 Hz, Me), 2.43 (q, JHH = 7.5 Hz,
3
3
CH arom), 7.79 (d, JHH = 8.2 Hz, 2 CH arom), 10.06 (s,
CH2), 4.54 (s, CH2), 6.34 (d, JHH = 1.7 Hz, CH furan),
NH) ppm; 13C NMR: d = 31.3 (CH2), 31.9 (CH2S), 51.5
(MeO), 54.3 (MeO), 128.1 (2 CH arom), 130.2 (2 CH
arom), 145.1 (C), 161.4 (C=O), 169.8 (C=O), 203.3 (C=S)
ppm.
6.36 (t, 3JHH = 3.6 Hz, CH furan), 7.38 (d, 3JHH = 1.8 Hz,
CH furan), 9.54 (s, NH) ppm; 13C NMR: d = 9.1 (Me),
30.4 (CH2), 34.8 (CH2), 109.7 (CH furan), 111.2 (CH
furan), 143.0 (CH furan), 171.2 (C=O), 203.8 (C=S) ppm.
(Furan-2-yl)methyl (4-methoxybenzoyl)
carbamodithioate (3n, C14H13NO3S2)
3-Mercaptopropyl propionylcarbamodithioate
(3r, C7H13NOS3)
Yellow oil; Rf: 0.71; yield: 0.48 g (78%); IR (KBr):
vꢀ = 3391 (NH), 1693 (C=O), 1145 (C=S) cm-1; EI-MS:
m/z (%) = 307 (7, M?), 240 (34), 226 (26), 204 (50), 172
(29), 135 (100), 103 (43), 81 (19), 67 (38); 1H NMR:
d = 3.77 (s, MeO), 4.61 (s, CH2), 6.34 (d, 3JHH = 1.4 Hz,
Yellow oil; Rf: 0.77; yield: 0.35 g (76%); IR (KBr):
vꢀ = 3430 (NH), 1710 (C=O), 1152 (C=S) cm-1; EI-MS:
m/z (%) = 223 (12, M?), 190 (13), 177 (28), 176 (52), 166
(33), 116 (25), 107 (51), 57 (100), 47 (19), 46 (38), 33 (21);
3
1H NMR: d = 1.23 (t, JHH = 8.7 Hz, Me), 1.45 (t,
3
3
3JHH = 7.2 Hz, SH), 2.08 (qui, JHH = 7.5 Hz, CH2),
CH furan), 6.39 (t, JHH = 3.3 Hz, CH furan), 7.33 (d,
3JHH = 8.08 Hz, 2 CH arom), 7.39 (d, 3JHH = 1.8 Hz, CH
furan), 7.79 (d, 3JHH = 8.5 Hz, 2 CH arom), 10.07 (s, NH)
ppm; 13C NMR: d = 34.9 (CH2), 53.9 (MeO), 109.8 (CH
furan), 111.4 (CH furan), 128.2 (2 CH arom), 130.3 (2 CH
arom), 142.9 (CH furan), 144.7 (C), 163.8 (C=O), 203.2
(C=S) ppm.
3
2.44 (q, JHH = 7.5 Hz, CH2), 2.68 (q, JHH = 8.3 Hz,
3
3
CH2), 3.38 (t, JHH = 7.0 Hz, CH2S), 9.46 (s, NH) ppm;
13C NMR: d = 8.9 (Me), 24.2 (CH2), 30.5 (CH2), 31.8
(CH2), 35.6 (CH2), 170.7 (C=O), 203.8 (C=S) ppm.
General procedure for the preparation of trimethylene
bisacylcarbamodithioates 5
3-Mercaptopropyl (4-methoxybenzoyl)
carbamodithioate (3o, C12H15NO2S3)
To a stirred solution of 0.30 g NH4SCN (4 mmol) in
20 cm3 MeCN was added 4 mmol acid chloride 1. The
mixture was stirred at rt for 30 min. Then, 2 mmol
1,3-propanedithiol (2c) was added and the reaction mixture
was stirred for 2 h at rt. The solvent was removed under
reduced pressure and the residue was purified by column
chromatography (SiO2, n-hexane–EtOAc 2:1) to afford the
pure title compounds.
Yellow oil; Rf: 0.71; yield: 0.45 g (75%); IR (KBr): vꢀ = 3382
(NH), 1690(C=O), 1149(C=S) cm-1; EI-MS: m/z (%) = 301
(11, M?), 268 (18), 255 (27), 254 (44), 194 (35), 135 (100),
1
107 (19), 47 (38), 46 (27), 33 (12); H NMR: d = 1.48 (t,
3
3JHH = 7.3 Hz, SH), 2.12 (qui, JHH = 7.1 Hz, CH2), 2.72
3
3
(q, JHH = 7.3 Hz, CH2), 3. 45 (t, JHH = 7.25 Hz, CH2S),
3.61 (s, MeO), 7.33 (d, 3JHH = 8.5 Hz, 2 CH arom), 7.80 (d,
3JHH = 8.5 Hz, 2 CH arom), 10.07 (s, NH) ppm; 13C NMR:
d = 24.3 (CH2), 31.8 (CH2S), 35.8 (CH2), 54.1 (MeO), 128.4
(2 CH arom), 130.5 (2 CH arom), 145.3 (C), 163.7 (C=O),
204.2 (C=S) ppm.
Trimethylene bis(2-fluorobenzoyl)carbamodithioate
(5a, C19H16F2N2O2S4)
Yellow powder; Rf: 0.52; yield: 0.38 g (81%); mp 175–
177 °C; IR (KBr): vꢀ = 3393 (NH), 1690, 1659 (C=O),
1152 (C=S) cm-1; EI-MS: m/z (%) = 470 (M?, 4), 347
(89), 289 (56), 166 (77), 123 (100), 108 (66), 58 (91), 43
2-(Methoxycarbonyl)ethyl propionylcarbamodithioate
(3p, C8H13NO3S2)
Yellow oil; Rf: 0.56; yield: 0.36 g (76%); IR (KBr):
vꢀ = 3430 (NH), 1723, 1693 (C=O), 1152 (C=S) cm-1; EI-
1
3
(64); H NMR: d = 2.31 (qui, JHH = 7.5 Hz, CH2), 3.47
123

1204
I. Yavari et al.
3
(t, JHH = 7.4 Hz, 2 CH2S), 7.19–7.26 (m, 2 CH arom),
1151 (C=S) cm-1; EI-MS: m/z (%) = 494 (M?, 5), 359
1
(39), 301 (50), 166 (57), 135 (100), 108 (61), 58 (46); H
7.33–7.38 (m, 2 CH arom), 7.59–7.66 (m, 2 CH arom),
8.12–8.18 (m, 2 CH arom), 10.58 (d, 5JHF = 15 Hz, 2 NH)
ppm; 13C NMR: d = 25.5 (CH2), 36.4 (2 CH2S), 116.2
(d, 2JCF = 24.3 Hz, CH), 118.4 (d, 2JCF = 9.6 Hz, C), 125.0
3
NMR: d = 2.31 (qui, JHH = 7.5 Hz, CH2), 3.59 (t,
3JHH = 7.5 Hz, 2 CH2S), 3.73 (s, 2 MeO), 7.32 (d,
3
3JHH = 8.5 Hz, 4 CH arom), 7.79 (d, JHH = 8.5 Hz, 4
4
3
(d, JCF = 3.0 Hz, CH), 133.6 (d, JCF = 9.1 Hz, CH),
CH arom), 10.06 (s, 2 NH) ppm; 13C NMR: d = 23.9
(CH2), 31.9 (2 CH2S), 54.3 (2 MeO); 128.1 (4 CH arom),
131.4 (4 CH arom), 146.3 (2 C), 164.7 (2 C=O), 204.5
(2 C=S) ppm.
3
136.8 (d, JCF = 9.5 Hz, CH), 159.0 (d, JCF = 248.4 Hz,
3
C–F), 166.5 (d, JCF = 3.1 Hz, C=O), 203.4 (2 C=S) ppm.
1
Trimethylene bispivaloylcarbamodithioate
(5b, C15H26N2O2S4)
Trimethylene bispropionylcarbamodithioate
(5f, C11H18 N2O2S4)
Yellow powder; Rf: 0.83; yield: 0.63 g (80%); mp 143–
146 °C; IR (KBr): vꢀ = 3395 (NH), 1700, 1691 (C=O),
1153 (C=S) cm-1; EI-MS: m/z (%) = 394 (M?, 6), 309
Yellow powder; Rf: 0.78; yield: 0.55 g (81%); mp 160–
162 °C; IR (KBr): vꢀ = 3438 (NH), 1699, 1716, (C=O), 1154
(C=S) cm-1; EI-MS: m/z (%) = 338 (M?, 4), 281 (59), 223
1
(89), 251 (56), 166 (77), 108 (40), 85 (100), 58 (64); H
3
1
NMR: d = 1.31 (s, 2 CMe3), 2.14 (qui, JHH = 7.4 Hz,
CH2), 3.42 (t, JHH = 7.5 Hz, 2 CH2S), 9.54 (s, 2 NH)
(52), 166 (71), 106 (30), 57 (100); H NMR: d = 1.24 (t,
3
3JHH = 8.7 Hz, 2 Me), 2.43 (q, 3JHH = 8.5 Hz, 2 CH2), 2.68
ppm; 13C NMR: d = 24.2 (CH2), 27.4 (2 CMe3), 31.7 (2
CH2S), 40.2 (2 CMe3), 175.6 (2 C=O), 204.6 (2 C=S) ppm.
(qui, JHH = 7.6 Hz, CH2), 3.38 (t, JHH = 7.5 Hz, 2
CH2S), 9.49 (s, 2 NH) ppm; 13C NMR: d = 8.9 (2 Me),
24.2 (CH2), 31.7 (2 CH2S), 35.5 (2 CH2), 170.8 (2 C=O),
203.8 (2 C=S) ppm.
3
3
Trimethylene bisbenzoylcarbamodithioate
(5c, C19H18 N2O2S4)
Yellow powder; Rf: 0.69; yield: 0.75 g (86%); mp 162–
164 °C; IR (KBr): vꢀ = 3406 (NH), 1700, 1686 (C=O), 1145
(C=S) cm-1; EI-MS: m/z (%) = 434 (M?, 3), 329 (59), 271
(38), 166 (61), 105 (100), 58 (41); 1H NMR: d = 2.32 (qui,
References
1. Aboul-Fadl T, El-Shorbagi A (1996) Eur J Med Chem 31:165
2. Len C, Boullognemerlot A, Posted D (1996) J Agric Food Chem
44:2856
3. Hidaka S, Fonakoshi T, Shimada H, Tsuruoka M, Kojima S
(1995) J Appl Toxicol 15:267
3
3JHH = 7.5 Hz, CH2), 3.48 (t, JHH = 7.5 Hz, 2 CH2S),
7.52–7.57 (m, 4 CH arom), 7.62–7.67 (m, 2 CH arom), 7.89–
7.92 (m, 4 CH arom), 10.07 (s, 2 NH) ppm; 13C NMR:
d = 25.7 (CH2), 36.4 (2 CH2S), 128.1, 129.6, 132.0, 133.9 (2
C6H5), 163.8 (2 C=O), 203.9 (2 C=S) ppm.
4. Tandon SK, Singh S, Jain VK, Prasad S (1996) Fundam Appl
Toxicol 31:141
5. Rafin C, Veignie E, Sanchelle M, Postal D, Len C, Villa P, Ronco
G (2000) J Agric Food Chem 48:5283
6. Cao SL, Feng YP, Jiang YY, Liu SY, Dind GY, Li RT (2005)
Bioorg Med Chem Lett 15:1915
7. Meng XM, Liu L, Hu HY, Zhu MZ, Wang MX, Shi J, Guo QX
(2006) Tetrahedron Lett 47:7961
8. Hua D, Sun W, Bai R, Lu W, Pan C (2005) Eur Polymer J
41:1674
9. Cao SL, Feng YP, Jiang YY, Liu SY, Ding GY, Li RT (2005)
Bioorg Med Chem Lett 15:1915
10. Yordanov AT, Falana OM, Koch HF, Roundhill DM (1997) Inorg
Chem 36:6468
Trimethylene bis(4-nitrobenzoyl)carbamodithioate
(5d, C19H16 N4O6S4)
Yellow powder; Rf: 0.60; yield: 0.93 g (89%); mp 187–
189 °C; IR (KBr): vꢀ = 3386 (NH), 1710, 1694 (C=O),
1149 (C=S) cm-1; EI-MS: m/z (%) = 524 (M?, 4), 374
(89), 316 (56), 166 (77), 150 (100), 108 (42), 58 (51), 43
1
3
(34); H NMR: d = 2.45 (qui, JHH = 7.5 Hz, CH2), 3.51
(t, 3JHH = 7.5 Hz, 2 CH2S), 8.08 (d, 3JHH = 8.9 Hz, 4 CH
3
arom), 8.41 (d, JHH = 8.9, 4 CH arom), 9.98 (s, 2 NH)
ppm; 13C NMR: d = 24.1 (CH2), 31.4 (2 CH2S), 128.6 (4
CH arom), 130.2 (4 CH arom), 151.7 (2 C-NO2), 171.3 (2
C=O), 202.9 (2 C=S) ppm.
11. Yavari I, Hosseini N, Moradi L (2008) Monatsh Chem 139:133
12. Yavari I, Hajinasiri R, Sayyed-Alangi SZ, Iravani N (2008)
Monatsh Chem 139:1029
13. Yavari I, Sayyed-Alangi SZ, Sabbaghan M, Hajinasiri R, Iravani
N (2008) Monatsh Chem 139:1025
14. Yavari I, Bagheri M, Porshamsian Kh, Ali-Askari S (2007)
J Sulfur Chem 28:269
15. Petrakis L, Sederholm CH (1961) J Chem Phys 35:1243
Trimethylene bis(4-methoxybenzoyl)carbamodithioate
(5e, C21H22 N2O4S4)
Yellow powder; Rf: 0.62; yield: 0.83 g (84%); mp 178–
180 °C; IR (KBr): vꢀ = 3430 (NH), 1700, 1731 (C=O),
123