An efficient, four-component reaction for the synthesis of novel carbamodithioates

Article abstract of DOI:10.1080/17415993.2016.1225215

A series of substituted phenylcarbamoyl methyl benzylcarbamodithioates have been synthesized using the multicomponent condition. The reaction proceeded under mild practical condition and afforded the desired products in good yields.

Full text of DOI:10.1080/17415993.2016.1225215

Journal of Sulfur Chemistry
ISSN: 1741-5993 (Print) 1741-6000 (Online) Journal homepage: http://www.tandfonline.com/loi/gsrp20
An efficient, four-component reaction for the
synthesis of novel carbamodithioates
Seyed Esmail Sadat-Ebrahimi, Leila Karim, Setareh Moghimi, Azadeh Yahya-
Meymandi, Mohammad Mahdavi, Mohsen Vosooghi, Alireza Foroumadi &
Abbas Shafiee
To cite this article: Seyed Esmail Sadat-Ebrahimi, Leila Karim, Setareh Moghimi, Azadeh Yahya-
Meymandi, Mohammad Mahdavi, Mohsen Vosooghi, Alireza Foroumadi & Abbas Shafiee
(2016): An efficient, four-component reaction for the synthesis of novel carbamodithioates,
Journal of Sulfur Chemistry, DOI: 10.1080/17415993.2016.1225215
To link to this article: http://dx.doi.org/10.1080/17415993.2016.1225215
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Date: 08 September 2016, At: 07:08

JOURNAL OF SULFUR CHEMISTRY, 2016
http://dx.doi.org/10.1080/17415993.2016.1225215
An efficient, four-component reaction for the synthesis of
novel carbamodithioates
Seyed Esmail Sadat-Ebrahimia, Leila Karima, Setareh Moghimib,
Azadeh Yahya-Meymandia, Mohammad Mahdavic, Mohsen Vosooghib,
Alireza Foroumadib,c and Abbas Shafieeb
aSchool of pharmacy, International Campus, Tehran University of Medical Sciences (TUMS-IC), Tehran, Iran;
bDepartment of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center,
Tehran University of Medical Sciences, Tehran, Iran; cDrug Design and Development Research Center, Tehran
University of Medical Sciences, Tehran, Iran
ABSTRACT
ARTICLE HISTORY
Received 8 May 2016
Accepted 13 August 2016
A series of substituted phenylcarbamoyl methyl benzylcarbamodi-
thioates have been synthesized using the multicomponent condi-
tion. The reaction proceeded under mild practical condition and
afforded the desired products in good yields.
KEYWORDS
Dithiocarbamate;
four-component; one-pot;
CS2; chloroacetyl chloride
1. Introduction
The multi-component reaction (MCR) plays an undeniable role for the interfacing of
chemistry with biology to introduce novel biologically active molecules [1]. The advan-
tageous features of this reaction make this protocol well suited for the one-pot generation
of drug targets. Despite the presence of few drugs based on multicomponent synthesis in
the market [2], there is an ever increasing effort directed toward combinatorial library con-
struction [3,4] with the hopes for finding interesting scaffolds, exhibiting reasonable levels
of bioactivities.
In the literature, dithiocarbamates have been identified as a potent building block in
a number of useful biomolecules [5–16]. The presence of this moiety in phytoalexins
brassinin [17–22], the antimicrobial agent produced by genus Brassica in the case of expo-
sure to chemical and biological stress [23,24], along with its incorporation as a side chain
into various cores [25] like quinazoline [26–29] and pyrrolidine [30] led to the significant
CONTACT Abbas Shafiee
ashafiee@ams.ac.ir
Supplemental data for this article can be accessed here. http://dx.doi.org/10.1080/17415993.2016.1225215
© 2016 Informa UK Limited, trading as Taylor & Francis Group

2
S. E. SADAT-EBRAHIMI ET AL.
cancer chemopreventive and cytotoxic activities. Dithiocarbamates have also found appli-
cations in organic synthesis mainly relying on their role as a mediator in carbamoyl radical
cyclization reactions [31]. Because of the important biological and synthetic applications of
dithiocarbamates, it is a highly desirable endeavor to synthesize such an important building
block in a simple and one-pot manner.
As part of our ongoing research program aimed at the synthesis of novel molecules,
[32–38] in this paper, we present a simple, four-component synthesis of substituted phenyl-
carbamoyl methyl benzylcarbamodithioates by the reaction of aniline derivatives, benzyl
amines, chloroacetyl chloride, and carbon disulfide.
2. Results and discussion
The reaction of anilines and chloroacetyl chloride produced compounds 3 upon stirring
at room temperature. The addition of carbon disulfide and benzyl amines to this pot
generated compounds 7 in good yields (Scheme 1).
In an effort to find the optimal reaction condition, we chose meta-anisidine 1b,
chloroacetyl chloride 2, carbon disulfide 4 and 4-methyl benzylamine 5b as model sub-
strates and tested the reaction in different solvents (including DMF, acetonitrile, acetone,
THF, ethanol and methanol) at room temperature. The sequence of the addition was also
important to achieve high yields in short reaction times. The results are given in Table 1.
By employing DMF as the medium, the reaction proceeded rapidly and afforded the prod-
uct in high yield (Table 1, entry 1). DMF is effective for this reaction, due to the stabilizing
effect of this solvent and its ability to solubilize intermediate salt 6. Other solvents were less
effective in terms of the isolated yields and reaction times (Table 1, entries 2–6).
Scheme 1. One-pot, four-component synthesis of carbamodithioates.

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3
Table 1. Solvent screening.a
Entry
Solvent
DMF
Acetonitrile
Ethanol
Methanol
Acetone
THF
Time (h)
Yield (%)b
1
2
3
4
5
6
1
3
8
6
12
12
81
54
51
47
38
31
aReactions were run at room temperature.
bIsolated yields.
Table 2. Substrate scope of the reaction (Scheme 1).
Compound
Ar1
Ar2
Time (min)
Yield (%)a
7a
7b
7c
7d
7e
7f
7g
7h
7i
7j
7k
7l
7m
7n
7o
7p
7q
C6H5
C6H5
C6H5
C6H5
4-MeC6H4
4-ClC6H4
C6H5
4-MeC6H4
4-ClC6H4
C6H5
4-MeC6H4
4-ClC6H4
4-MeC6H4
C6H5
4-MeC6H4
4-ClC6H4
C6H5
70
90
120
90
70
75
68
74
81
70
68
69
65
71
70
75
69
71
76
70
67
3-MeOC6H4
3-MeOC6H4
3-MeOC6H4
2-FC6H4
2-FC6H4
2-FC6H4
3-ClC6H4
2,5-Cl2C6H3
2,5-Cl2C6H3
2,5-Cl2C6H3
3,4-Cl2C6H3
3,4-Cl2C6H3
3,4-Cl2C6H3
4-BrC6H4
60
105
140
100
160
120
130
110
170
130
120
150
180
4-MeC6H4
4-ClC6H4
C6H5
aIsolated yields.
For library construction, the optimized condition was used for different commer-
cially available primary amines. The presence of both electron-withdrawing and electron-
donating groups in these compounds at different positions led to the easy generation of the
desired products 7a–7q (Table 2). Electron-donating groups gave rise to the corresponding
products in higher yields.
1
The structure of compounds 7a–7q were confirmed by IR, H-NMR and 13C-NMR
1
spectroscopy. The H-NMR spectrum of compound 7p exhibited two singlet peaks for
the methylene groups at 4.26 and 4.83 ppm along with characteristic signals for aryl and
NH protons (9.99 and 10.62 ppm). The 13C NMR spectrum of this compound exhibited
characteristic signals for CH2S at 40 ppm and CH2N at 49 ppm in the aliphatic region. The
=
=
C O and C S groups appeared at 166 and 196 ppm, respectively, along with 10 aromatic
carbons.

4
S. E. SADAT-EBRAHIMI ET AL.
3. Conclusion
In conclusion, we have developed an efficient one-pot, four-component synthesis of sub-
stituted phenylcarbamoyl methyl benzylcarbamodithioates. Given the large number of
commercially available aniline and benzyl amines derivatives, this method was applicable
for the synthesis of a library of compound 7.
4. Experimental
1
Melting points were taken on a Kofler hot-stage apparatus and are uncorrected. H and
13C NMR spectra were recorded on a Bruker FT-500, using tetramethylsilane (TMS) as
an internal standard. The infrared (IR) spectra were obtained on a Nicolet Magna FT-IR
550 spectrophotometer (KBr disks). Mass spectra were recorded on an Agilent Technology
(HP) mass spectrometer operating at an ionization potential of 70 eV. Elemental analyses
were carried out with a Perkin-Elmer model 240-C apparatus.
4.1. General procedure for the synthesis of compounds 7a–7q
To a stirred solution of substituted aniline (1 mmol) and chloroacetyl chloride (1 mmol)
which was stirred in 5 mL DMF for 20 min, were added benzyl amine derivatives
(1.3 mmol) and CS2 (5 mmol). The reaction mixture was allowed to stir for required addi-
tional time (Table 2). Then, 5 mL of water was added and the solution was extracted with
ethyl acetate and dried over sodium sulfate and purified by passing over a silica gel column
chromatography using petroleum ether/ethyl acetate (8:2).
4.1.1. (Phenylcarbamoyl)methyl benzylcarbamodithioate (7a)
Colorless powder; Yield 70%; mp 122–124°C; IR (KBr, cm−1): 3206, 1666, 1600, 1537, 1495,
1442, 1394, 1328, 922, 750, 690; 1H NMR (500 MHz, CDCl3): δ 4.07 (s, 2H, CH2S), 4.92
(d, J = 5.0 Hz, 2H, CH2NH), 7.10 (t, J = 7.5 Hz, 1H, H4Ar1 ), 7.25–7.36 (m, 7H), 7.49 (d,
J = 8.5 Hz, 2H, H2,6Ar1 ), 7.82 (brs, NH), 8.76 (s, NH). EI-MS: 316 (M+, 18), 182 (33), 134
(100), 106 (56), 92 (62), 77 (45). Anal. calcd. for C16H16N2OS2: C 60.73, H 5.10, N 8.85;
found: C 60.64, H 5.19, N 8.78.
4.1.2. (Phenylcarbamoyl)methyl 4-methylbenzylcarbamodithioate (7b)
Colorless powder; Yield 75%; mp 115–117°C; IR (KBr, cm−1): 3148, 1676, 1601, 1546,
1518, 1497, 1442, 1356, 941, 831, 750; 1H NMR (500 MHz, CDCl3): δ 2.17 (s, 3H, CH3),
4.08 (s, 2H, CH2S), 4.87 (d, J = 5.0 Hz, 2H, CH2NH), 7.11 (t, J = 7.5 Hz, 1H, H4Ar1 ),
7.17 (d, J = 8.5 Hz, 2H, H3,5Ar2 ), 7.22 (d, J = 8.5 Hz, 2H, H
2,6Ar2 ), 7.31 (t, J = 7.5 Hz, 2H,
2,6Ar1 ), 7.73 (brs, NH), 8.79 (s, NH). Anal. calcd. for
H3,5Ar1 ), 7.50 (d, J = 7.5 Hz, 2H, H
C17H18N2OS2: C 61.79, H 5.49, N 8.48; found: C 61.86, H 5.60, N 8.55.
4.1.3. (Phenylcarbamoyl)methyl 4-chlorobenzylcarbamodithioate (7c)
Colorless powder; Yield 68%; mp 130–131°C; IR (KBr, cm−1): 3247, 1643, 1600, 1519,
1
1497, 1443, 1326, 918, 832, 754; H NMR (500 MHz, DMSO-d6): δ 4.20 (s, 2H, CH2S),
4.83 (s, 2H, CH2NH), 7.06 (t, J = 7.5 Hz, 1H, H4Ar1 ), 7.29 (d, J = 8.0 Hz, 2H, H2,6Ar2 ),
7.33 (d, J = 8.0 Hz, 2H, H3,5Ar2 ), 7.39 (t, J = 8.0 Hz, 2H, H
3,5Ar1 ), 7.57 (d, J = 8.0 Hz, 2H,

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5
H2,6Ar1 ), 10.22 (s, NH), 10.59 (brs, NH). 13C NMR (125 MHz, DMSO-d6): δ 39.4 (CH2S),
=
48.9 (CH2N), 119.1, 123.4, 127.9, 128.8, 129.1, 131.7, 136.1, 138.8, 165.7 (C O), 196.2
(C S). Anal. calcd. for C16H15ClN2OS2: C 54.77, H 4.31, N 7.98; found: C 54.83, H 4.40,
N 8.06.
=
4.1.4. (3-Methoxyphenylcarbamoyl)methyl benzylcarbamodithioate (7d)
Colorless powder; Yield 74%; mp 80–82°C; IR (KBr, cm−1): 3142, 1677, 1610, 1521, 1495,
1326, 1283, 1206, 1085, 936, 752, 694; 1H NMR (500 MHz, CDCl3): δ 3.79 (s, 3H, OCH3),
4.06 (s, 2H, CH2S), 4.91 (d, J = 5.0 Hz, 2H, CH2NH), 6.6 (d, J = 8.0 Hz, 1H, H4Ar1 ), 6.97
(d, J = 8.0 Hz, 1H, H6Ar1 ), 7.19 (t, J = 8.0 Hz, 1H, H
5Ar1 ), 7.25 (d, J = 3.0 Hz, 1H, H2Ar1 ),
7.32–7.36 (m, 5H), 8.02 (brs, NH), 8.83 (s, NH). Anal. calcd. for C17H18N2O2S2: C 58.93,
H 5.24, N 8.09; found: C 58.99, H 5.17, N 8.16.
4.1.5. (3-Methoxyphenylcarbamoyl)methyl 4-methylbenzylcarbamodithioate (7e)
Colorless powder; Yield 81%; mp 114–116°C; IR (KBr, cm−1): 3266, 1660, 1611, 1548, 1514,
1464, 1322, 1212, 916, 845, 753; 1H NMR (500 MHz, DMSO-d6): δ 2.28 (s, 3H, CH3), 3.73
(s, 3H, OCH3), 4.17 (s, 2H, CH2S), 4.78 (d, J = 5.5 Hz, 2H, CH2NH), 6.64 (dd, J = 8.5,
2.3 Hz, 1H, H4Ar1 ), 7.08 (d, J = 7.5 Hz, 1H, H
6Ar1 ), 7.13 (d, J = 8.5 Hz, 2H, H3,5Ar2 ), 7.19
2Ar1 ), 7.26 (m, 1H, H5Ar1 ), 10.19 (s, NH), 10.52
(d, J = 8.5 Hz, 2H, H2,6Ar2 ), 7.22 (m, 1H, H
(t, J = 5.5 Hz, NH). Anal. calcd. for C18H N2O2S2: C 59.97, H 5.59, N 7.77; found: C
20
60.04, H 5.66, N 7.89.
4.1.6. (3-Methoxyphenylcarbamoyl)methyl 4-chlorobenzylcarbamodithioate (7f)
Colorless powder; Yield 70%; mp 104–106°C; IR (KBr, cm−1): 3220, 1674, 1609, 1523, 1494,
1426, 1326, 1283, 1088, 931, 843; 1H NMR (500 MHz, CDCl3): δ 3.78 (s, 3H, OCH3), 4.03
(s, 2H, CH2S), 4.89 (d, J = 5.0 Hz, 2H, CH2NH), 6.67 (dd, J = 7.5, 2.0 Hz, 1H, H 1 ),
6.95 (d, J = 7.5 Hz, 1H, H6Ar1 ), 7.18–7.22 (m, 2H), 7.26–7.27 (m, 2H), 7.32 (d, J = 8.40AHr z,
2H, H2,6Ar2 ), 8.33 (brs, NH), 8.78 (s, NH). Anal. calcd. for C H ClN2O2S2: C 53.60, H
17 17
4.50, N 7.35; found: C 53.71, H 4.57, N 7.47.
4.1.7. (2-Fluorophenylcarbamoyl)methyl benzylcarbamodithioate (7g)
Colorless powder; Yield 68%; mp 128–130°C; IR (KBr, cm−1): 3200, 1704, 1617, 1536,
1
1496, 1376, 1346, 1299, 1193, 754; H NMR (500 MHz, DMSO-d6): δ 4.26 (s, 2H,
CH2S), 4.85 (s, 2H, CH2NH), 7.15–7.18 (m, 2H), 7.23–7.26 (m, 2H), 7.28–7.35 (m, 4H),
7.88–7.90 (m, 1H), 9.99 (s, NH), 10.59 (brs, NH). 13C NMR (125 MHz, DMSO-d6): δ 40.3
(CH2S), 49.8 (CH2N), 115.4, 123.7, 124.3, 125.3, 125.8, 127.3, 128.2, 128.4, 137.1, 154.4 (d,
=
=
JC−F = 225 Hz), 166.4 (C O), 195.9 (C S). Anal. calcd. for C16H15FN2OS2: C 57.46, H
4.52, N 8.38; found: C 57.38, H 4.65, N 8.29.
4.1.8. 4(2-Fluorophenylcarbamoyl)methyl 4-methylbenzylcarbamodithioate (7h)
Colorless powder; Yield 69%; mp 119–121°C; IR (KBr, cm−1): 3185, 1665, 1539, 1525,
1490, 1457, 1330, 908, 824, 760; 1H NMR (500 MHz, CDCl3): δ 2.35 (s, 3H, CH3), 4.15
(s, 2H, CH2S), 4.87 (s, 2H, CH2NH), 7.06–7.11 (m, 3H), 7.16–7.58 (m, 4H), 7.58 (m,
1H), 8.25 (brs, NH), 8.77 (s, NH). 13C NMR (125 MHz, CDCl3): δ 21.1 (CH3), 39.2
(CH2S), 52.0 (CH2N), 114.8, 115.0, 121.9, 124.5, 128.0, 128.3, 129.7, 132.5, 138.2, 156.9

6
S. E. SADAT-EBRAHIMI ET AL.
=
=
(d, JC−F = 250 Hz), 167.1 (C O), 196.0 (C S). Anal. calcd. for C17H17FN2OS2: C 58.60,
H 4.92, N 8.04; found: C 58.53, H 5.01, N 8.11.
4.1.9. (2-Fluorophenylcarbamoyl)methyl 4-chlorobenzylcarbamodithioate (7i)
Colorless powder; Yield 65%; mp 100–103°C; IR (KBr, cm−1): 1676, 1633, 1489, 1456, 1328,
1083, 925, 752; 1H NMR (500 MHz, DMSO-d6): 4.26 (s, 2H, CH2S), 4.85 (d, J = 5.5 Hz,
2H, CH2NH), 7.15–7.17 (m, 2H), 7.23–7.26 (m, 1H), 7.30 (d, J = 7.5 Hz, 2H, H
2 ), 7.39
(d, J = 7.5 Hz, 2H, H3,5Ar2 ), 7.86–7.90 (m, 1H), 9.98 (s, NH), 10.61 (t, J = 5.25,6HArz, NH).
13C NMR (125 MHz, DMSO-d6): 49.0 (CH2S), 66.9 (CH2N), 115.4, 123.7, 124.3, 125.3,
=
=
125.9, 128.1, 128.4, 129.2, 136.1, 159.2 (d, JC−F = 212 Hz), 166.4 (C O), 196.1 (C S).
Anal. calcd. for C16H14ClFN2OS2: C 52.10, H 3.83, N 7.59; found: C 51.99, H 3.92, N 7.48.
4.1.10. (3-Chlorophenylcarbamoyl)methyl 4-methylbenzylcarbamodithioate (7j)
Colorless powder; Yield 71%; mp 115–117°C; IR (KBr, cm−1): 3225, 1657, 1643, 1592, 1532,
1426, 1368, 1319, 916, 822, 781; 1H NMR (500 MHz, DMSO-d6): δ 2.28 (s, 3H, CH3), 4.20
(s, 2H, CH2S), 4.78 (d, J = 4.0 Hz, 2H, CH2NH), 7.12 (d, J = 7.5 Hz, 2H, H3,5Ar2 ), 7.18 (d,
J = 7.5 Hz, 2H, H2,6Ar2 ), 7.32–7.35 (m, 2H), 7.43 (d, J = 7.5 Hz, 1H, H
4Ar1 ), 7.79 (s, 1H,
H2Ar1 ), 10.42 (brs, NH), 10.55 (s, NH). 13C NMR (125 MHz, DMSO-d6): δ 20.6 (CH3),
40.6 (CH2S), 49.6 (CH2N), 118.5, 123.0, 127.7, 128.8, 130.3, 130.5, 133.0, 134.0, 136.3,
=
=
140.3, 166.2 (C O), 195.6 (C S). Anal. calcd. for C17H17ClN2OS2: C 55.95, H 4.70, N
7.68; found: C 56.03, H 4.59, N 7.76.
4.1.11. (2,5-Dichlorophenylcarbamoyl)methyl benzylcarbamodithioate (7k)
Colorless powder; Yield 70%; mp 107–109°C; IR (KBr, cm−1): 3210, 1680, 1582, 1519, 1452,
1404, 1368, 1093, 1058, 917, 754; 1H NMR (500 MHz, CDCl3): δ 4.23 (s, 2H, CH2S), 4.92
(d, J = 4.5 Hz, 2H, CH2NH), 7.32–7.37 (m, 7H), 7.51 (s, 1H, H6Ar1 ), 8.87 (s, NH), 8.93
(brs, NH). 13C NMR (125 MHz, CDCl3): δ 39.4 (CH2S), 52.2 (CH2N), 121.7, 124.8, 125.4,
=
=
128.3, 128.4, 129.0, 129.8, 129.8, 134.5, 135.5, 167.0 (C O), 195.6 (C S). Anal. calcd. for
C16H14Cl2N2OS2: C 49.87, H 3.66, N 7.27; found: C 49.98, H 3.73, N 7.16.
4.1.12. (2,5-Dichlorophenylcarbamoyl)methyl 4-methylbenzylcarbamodithioate (7l)
Colorless powder; Yield 75%; mp 131–133°C; IR (KBr, cm−1): 3215, 1673, 1579, 1523, 1448,
1409, 1369, 1089, 1043, 927, 854, 742; 1H NMR (500 MHz, DMSO-d6): δ 2.27 (s, 3H, CH3),
4.27 (s, 2H, CH2S), 4.79 (d, J = 5.5 Hz, 2H, CH2NH), 7.13 (d, J = 8.0 Hz, 2H, H3,5Ar2 ),
7.18 (d, J = 8.0 Hz, 2H, H2,6Ar2 ), 7.26 (dd, J = 9.0, 2.0 Hz, 1H, H
4Ar1 ), 7.54 (d, J = 9.0 Hz,
1H, H3Ar1 ), 7.95 (d, J = 2.0 Hz, 1H, H 1 ), 9.77 (s, NH), 10.61 (t, J = 5.5 Hz, NH). 13
C
6Ar
NMR (125 MHz, DMSO-d6): δ 20.6 (CH3), 38.7 (CH2S), 49.7 (CH2N), 125.4, 125.6, 127.7,
=
=
128.8, 130.7, 130.8, 131.6, 133.9, 135.8, 136.4, 166.9 (C O), 195.3 (C S). Anal. calcd. for
C17H16Cl2N2OS2: C 51.13, H 4.04, N 7.01; found: C 51.18, H 4.09, N 6.92.
4.1.13. (2,5-Dichlorophenylcarbamoyl)methyl 4-chlorobenzylcarbamodithioate (7m)
Colorless powder; Yield 69%; mp 129–131°C; IR (KBr, cm−1):1680, 1583, 1519, 1490, 1453,
1366, 1093, 1072, 920, 842; 1H NMR (500 MHz, DMSO-d6): δ 4.28 (s, 2H, CH2S), 4.82 (s,
2H, CH2NH), 7.25 (d, J = 9.0 Hz, 1H, H4Ar1 ), 7.30 (d, J = 7.5 Hz, 2H, H2,6Ar2 ), 7.39 (d,
J = 7.5 Hz, 2H, H3,5Ar2 ), 7.55 (d, J = 9.0 Hz, 1H, H
3Ar1 ), 7.90 (s, 1H, H6Ar1 ), 9.96 (s, NH),
10.67 (brs, NH). 13C NMR (125 MHz, DMSO-d6): δ 40.1 (CH2S), 49.1 (CH2N), 123.7,

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7
=
=
124.8, 125.5, 126.4, 128.1, 129.6, 130.8, 131.6, 135.4, 145.9, 166.8 (C O), 195.9 (C S).
Anal. calcd. for C16H13Cl3N2OS2: C 45.78, H 3.12, N 6.67; found: C 45.84, H 3.04, N 6.72.
4.1.14. (3,4-Dichlorophenylcarbamoyl)methyl benzylcarbamodithioate (7n)
Colorless powder; Yield 71%; mp 102–104°C; IR (KBr, cm−1):3201, 1680, 1588, 1530, 1474,
1
1453, 1391, 1335, 811, 702; H NMR (500 MHz, DMSO-d6): δ 4.23 (s, 2H, CH2S), 4.84
(d, J = 5.5 Hz, 2H, CH2NH), 7.31–7.36 (m, 5H), 7.49 (dd, J = 9.0, 3.0 Hz, 1H, H 1 ),
7.56 (d, J = 9.0 Hz, 1H, H5Ar1 ), 7.98 (s, 1H, H 1 ), 10.57 (s, NH), 10.61 (t, J = 5.65AHr z,
2Ar
NH). 13C NMR (125 MHz, DMSO-d6): δ 40.1 (CH2S), 49.8 (CH2N), 119.2, 120.3, 124.8,
=
=
127.8, 128.2, 128.4, 130.6 (2C), 137.1, 138.9, 166.3 (C O), 195.8 (C S). Anal. calcd. for
C16H14Cl2N2OS2: C 49.87, H 3.66, N 7.27; found: C 49.94, H 3.58, N 7.33.
4.1.15. (3,4-Dichlorophenylcarbamoyl)methyl 4-methylbenzylcarbamodithioate (7o)
Colorless powder; Yield 76%; mp 120–122°C; IR (KBr, cm−1): 3197, 1670, 1595, 1536, 1476,
1
1392, 1378, 919, 894; H NMR (500 MHz, CDCl3): δ 2.32 (s, 3H), 4.07 (s, 2H, CH2S),
4.87 (s, 2H, CH2NH), 7.17 (d, J = 8.0 Hz, 2H, H3,5Ar2 ), 7.23 (d, J = 8.0 Hz, 1H, H6Ar1 ),
7.30–7.33 (m, 3H, H2,6Ar2 , H
1 ), 9.06 (brs, NH). 13
C
5Ar1 ), 7.64 (s, NH), 7.71 (s, 1H, H2Ar
NMR (125 MHz, CDCl3): δ 21.1 (CH3), 38.9 (CH2S), 50.9 (CH2N), 119.1, 121.5, 128.0,
=
=
128.3, 129.7, 129.9, 130.4, 132.2, 137.3, 138.4, 167.2 (C O), 196.7 (C S). Anal. calcd. for
C17H16Cl2N2OS2: C 51.13, H 4.04, N 7.01; found: C 51.19, H 4.00, N 6.95.
4.1.16. (3,4-Dichlorophenylcarbamoyl)methyl 4-chlorobenzylcarbamodithioate (7p)
Colorless powder; Yield 70%; mp 103–105°C; IR (KBr, cm−1): 3209, 1675, 1532, 1489,
1455, 1374, 1327, 1257, 1082, 830, 751, 623; 1H NMR (500 MHz, DMSO-d6): δ 4.26 (s, 2H,
CH2S), 4.83 (s, 2H, CH2NH), 7.15 (dd, J = 6.0, 3.0 Hz, 1H, H6Ar1 ), 7.30–7.33 (m, 3H), 7.40
(d, J = 8.5 Hz, 2H, H3,5Ar2 ), 7.49 (s, 1H, H 1 ), 9.99 (s, NH), 10.62 (brs, NH). 13C NMR
2Ar
(125 MHz, DMSO-d6): δ 40.4 (CH2S), 49.0 (CH2N), 115.4, 123.8, 124.2, 125.3, 128.1, 128.4,
=
=
129.3, 129.6, 131.7, 136.1, 166.4 (C O), 196.1 (C S). Anal. calcd. for C16H13Cl3N2OS2:
C 45.78, H 3.12, N 6.67; found: C 45.69, H 3.21, N 6.72.
4.1.17. (4-Bromophenylcarbamoyl)methyl benzylcarbamodithioate (7q)
Colorless powder; Yield 67%; mp 126–128°C; IR (KBr, cm−1): 3182, 1662, 1535, 1488, 1394,
1354, 1322, 922, 825, 699 ; 1H NMR (500 MHz, DMSO-d6): δ 4.21 (s, 2H, CH2S), 4.84 (d,
J = 5.5 Hz, 2H, CH2NH), 7.27–7.36 (m, 5H), 7.49 (d, J = 8.5 Hz, 2H, H2,6Ar2 ), 7.55 (d,
J = 8.5 Hz, 2H, H3,5Ar2 ), 10.38 (s, NH), 10.60 (t, J = 5.5 Hz, NH). 13C NMR (125 MHz,
DMSO-d6): δ 40.1 (CH2S), 49.8 (CH2N), 114.9, 121.0, 127.3, 127.8, 128.4, 131.4, 131.6,
=
=
137.1, 166.0 (C O), 195.9 (C S). Anal. calcd. for C16H15BrN2OS2: C 48.61, H 3.82, N
7.09; found: C 48.56, H 3.75, N 7.00.
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
This work was supported and funded by Research Council of International Campus, Tehran
University of Medical Sciences (TUMS-IC) and Iran National Science Foundation (INSF).

8
S. E. SADAT-EBRAHIMI ET AL.
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