A simple and eco-compatible one-pot synthesis of new symmetrical dithiocarbamate podands and their dynamic NMR studies

Article abstract of DOI:10.1080/10426507.2012.717133

A simple and eco-compatible synthesis of podands as 4a-_i is performed using amines (3a-_C), CS₂, and dichlordiamides (DCDs) (2a, _C) in the absence of a catalyst in water. Three reacting DCDs (2a-_C) wer

Full text of DOI:10.1080/10426507.2012.717133

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Phosphorus, Sulfur, and Silicon and the
Related Elements
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A Simple and Eco-Compatible One-
Pot Synthesis of New Symmetrical
Dithiocarbamate Podands and Their
Dynamic NMR Studies
Abbas Shockravi a , Mahmood Kamali a & Reza Jafari a
a Faculty of Chemistry , Kharazmi (Tarbiat Moallem) University ,
Tehran , Iran
Accepted author version posted online: 09 Aug 2012.Published
online: 16 Aug 2013.
To cite this article: Abbas Shockravi , Mahmood Kamali & Reza Jafari (2013) A Simple and Eco-
Compatible One-Pot Synthesis of New Symmetrical Dithiocarbamate Podands and Their Dynamic
NMR Studies, Phosphorus, Sulfur, and Silicon and the Related Elements, 188:9, 1271-1280, DOI:
10.1080/10426507.2012.717133
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Phosphorus, Sulfur, and Silicon, 188:1271–1280, 2013
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2012.717133
A SIMPLE AND ECO-COMPATIBLE ONE-POT SYNTHESIS
OF NEW SYMMETRICAL DITHIOCARBAMATE PODANDS
AND THEIR DYNAMIC NMR STUDIES
Abbas Shockravi, Mahmood Kamali, and Reza Jafari
Faculty of Chemistry, Kharazmi (Tarbiat Moallem) University, Tehran, Iran
GRAPHICAL ABSTRACT
Abstract A simple and eco-compatible synthesis of podands as 4a-i is performed using amines
(3a-c), CS2, and dichlordiamides (DCDs) (2a, c) in the absence of a catalyst in water. Three re-
acting DCDs (2a-c) were obtained in the reaction of aromatic diamines (1a, c) with chloroacetyl
chloride. Dynamic NMR spectroscopic data of three series of podands (4a-c, 4d-f, and 4g-i) are
discussed and their free energies of activations are calculated (ꢀG=c s) at coalescence temper-
atures. The ꢀG=c of these podands were attributed to conformational isomerization in the range
of 14.7–17 kcal/mol due to rotation and resonance effects about the thioamide C N bond.
[Supplementary materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfer, and Silicon and the Related Elements for the following free supplemental
files: Additional figures.]
Keywords Podand; didithiocarbamate; reaction in water; aromatic diamines; dynamic NMR;
free energies of activation (ꢀG=)
Received 15 April 2012; accepted 14 July 2012.
We thank the research council of the Kharazmi (Tarbiat Moallem) University for financial support.
Address correspondence to Abbas Shockravi, Faculty of Chemistry, Kharazmi (Tarbiat Moallem) University,
Tehran 15614, Iran. E-mail: abbas shockravi@yahoo.co.uk
1271

1272
A. SHOCKRAVI ET AL.
INTRODUCTION
Dithiocarbamates (DTCs) have received much attention due to their vast scope
and broad biological effects such as fungicidal,1–5 antibacterial,2,6–9 and anticancer ac-
tivities.6,10,11 It is believed that the antibacterial effect of DTCs results from the HS-groups
of physiologically important enzymes transferring the alkyl group of the dithioester to the
HS-function of the enzyme.6 Another application of DTCs is their strong ability to bind
metal ions and complexation with metals as monodentate and bidentate ligands.12
The general synthetic method for the preparation of DTCs involves using thiophos-
gene13,14 and its derivatives,15 which are toxic and expensive substrates. Moreover, their
synthesis using CS2 proceeds under harsh conditions such as using strong bases, high tem-
peratures, and long reaction times.16 General synthetic methods of vinyl and aryl esters of
dithiocarbamic acids are based upon the reactions of hypervalent iodine compounds with
the sodium salt of dithiocarbamic acid.17,18 Recently, some new and efficacious procedures
were published for the synthesis of DTCs.19
Investigations on structure–activity relationship have suggested that the distance
between functional groups was the main feature responsible in their pharmacological use-
fulness.20 Also, molecular flexibility plays an important role in biological activities which
is mainly dictated by hindered rotation about chemical bonds, such as conjugated C–N link-
ages.21–25 The C N bond character is due to delocalization of the nitrogen lone pair over
the N C S π bond, which makes the rotational barrier substantially higher than simple
amines.21–25 The C N rotational barrier in DTCs lies in the vicinity of 10–15 kcal/mol26,27
for carbamates,15 whereas in amides the values range from 15–22 kcal/mol.21,23,25,28,29–35
Because of the importance of DTCs and our previous research in the synthesis and
dynamic NMR (DNMR) studies on different DTCs podands,36 we were encouraged to
exploit the one-pot synthesis of three series of DTCs (4a-c, 4d-f, and 4g-i) in aqueous media
using the reacting diamines (1a-c; see Scheme 1). Also, we wish to report and discuss the
conformational behavior of these DTCs based on their rotational barrier energies about
thioamide C N bond.
RESULTS AND DISCUSSION
In this work, diamines (1a–c) reacted with chloroacetyl chloride at room temperature
and led to the formation of dichlorodiamides (2a–c) in 2 h. The DCDs (2a-c) easily reacted
with CS2 and secondary amines 3a–c at room temperature and produced the podands 4a–i
(Scheme 1 and Table 1). Also, the coalescence temperatures (TC) of nine podands 4a–i were
obtained from their corresponding DNMR spectra in the range of 308–350 K (Table 2).
The coalescence rate (Kc) is calculated according to the Gutowsky–Holm equation,
=
Tc
Kc
Kc = πꢀν . The Eyring equation, ꢀGc = 4.58 Tc(10.32 + log , was used to calculate
√
2
the ꢀG=c values (Table 2). ꢀGc= values (14–17 kcal/mol) for 4a–c, d–f, g–i, revealed that
different six-member rings do not affect on transition states and intermediates significantly.
The ꢀG=c values in Table 2 may reach the conclusion that CH2 groups are subjected
to the adjacent nitrogen atom and the amount of resonance phenomena due to competition
between S and N atoms. These data demonstrate that conversion of resonance forms shown
in Figure 1 takes place hardly at ambient temperature, while increasing the temperature is
influential on interconversion of resonance forms.
The 1H NMR study of compounds 4a–i in chloroform exhibit two distinct signals for
–CH2-protons, adjacent to nitrogen atom at 298 K. The chemical shifts of CH2 protons

ONE-POT SYNTHESIS OF SYMMETRICAL DTC PODANDS
1273
Scheme 1
(C-1 and C-2, Figure 1) for podands 4a, b, d–f, and g, h in CDCl3 at 298 K are listed in Table 2.
The temperature-dependent 1H NMR spectrum of podands 4d is shown in Figure 2. Typical
DNMR behavior of these podands exhibits the exchange broadening of the C-1 and C-2
methylene resonance. Below 334.5 K, two separate signals can be observed for C-1 and C-2,
while above 334.5 K, only one signal is observed representing fast exchange between the
two distinct magnetic environments. The maximum separation between protons attached
to C-1 and C-2 for these podands were observed below 298 K.
Table 2 also lists the experimental rate constants characterizing the internal rota-
tion around the C–N bond in compounds 4a-i in CDCl3 [in the cases of 4a, g, Tc was
above the boiling point of the NMR solvent (boiling point of CDCl3 = 334 K)]. Four
dynamic processes (thioamide rotation, nitrogen inversion, ring reversal, and rotation about
S C bond ( S C S, see Figure 1)) are possible in the derivatives of diethylamine
(4a, d, and g), piperidine (4b–e, h) and morpholine (4c, f, i). The nitrogen inversion barriers in
Figure 1 The four most important resonance structures for DTCs.

1274
A. SHOCKRAVI ET AL.
Table 1 List of synthesized podands
Entry Bis (chloroacetamide)
1.
Thione salt
DTC
Yield (%)
77
MP (◦C)
Viscous liquid
2.
3.
4.
92
91
87
153–155
180–182
186–187
5.
6.
7.
91
91
92
220
217–219
83–84.5

ONE-POT SYNTHESIS OF SYMMETRICAL DTC PODANDS
1275
Table 1 List of synthesized podands (Continued)
Entry
8.
Bis (chloroacetamide)
Thione salt
DTC
Yield (%)
91
MP (◦C)
171–173
9.
85
248–249
the derivatives of diethylamine, piperidines, and morpholine are too small37 to be observed
by DNMR. Ring-reversal barriers in piperidines and morpholines are observed with ꢀGc=
of 42.0–54.4 kJ mol−1. The S C bond rotation is fast in dithiocarbamtes, in which the S
atom is alkylated.27 In this study, the thioamide C N bond rotation was the only process
observed. The two other processes are expected to be too small to be directly observed by
DNMR. The resonance model (Figure 1) rationalized the large barrier for rotation about the
C N bond in thioamides as a significant contribution to the stability of the planar amide
from the resonance structure in which charge is transferred from the amidic N and S to
the thiocarbonyl C S via the π system. This predicts that the C–N bond length would
Figure 2 Dynamic 1H NMR for podands 4d.

1276
A. SHOCKRAVI ET AL.
Table 2 Data acquired from variable temperatures 1H NMR spectroscopy
∂
(ppm)
at 298 K
∂
(ppm)
HC-2
at 298 K
ꢀ (∂HC-1, ∂HC-2
(ppm) at 298 K
)
ꢀG=c
HC-1
Podand
TC (K)
KC (S−1
)
(cal mol−1
)
4a
4b
4c
4d
4e
4f
4g
4h
4i
3.63
3.71
3.98
3.79
3.92
3.98
3.70
3.83
3.91
3.95
4.29
4.38
4.06
4.30
4.35
3.93
4.19
4.24
0.27
0.58
0.4
0.27
0.38
0.37
0.23
0.36
0.33
>333∗
323
313
334
323
308
>333∗
318
180.82
381.52
262.02
176.49
255.37
243.72
150.31
243.79
220.87
>16.15∗
15.16
14.90
16.21
15.42
14.70
>16.27∗
15.20
308
14.76
∗Tc is higher than the boiling point of NMR solvent (CDCl3).
shorten. The C N bond seems to exhibit more double-bond character and bond length
would shorten than that in amides and carbamates. This is due to a greater contribution of
the dipolar canonical structure (c) in the resonance structures (Figure 3), because C(2p)-
S(3p) overlap in a thioamide bond is less effective than C(2p)-O(2p) overlap in an amide
bond. On the other hand, the C S bond will have only small polarization since the elec-
tronegativities of carbon and sulfur are about the same. Thus, the importance of structure
(b) is markedly reduced. A similar behavior has been observed in thioamides relative to
amides.38
According to Table 2, for compounds with piperidine or morpholine residues instead
of the ethylamine moiety, the ꢀG=c values are lower. In the case of piperidine or morpholine
derivatives (Figure 4), the chair conformation (of six-member rings) decreases the planarity
of the amidic nitrogen atom. The presence of oxygen instead of methylene (morpholine
vs. piperidine) decreases the participation of planar amidic form, and thus the resonance is
further weakened. This is probably due to the steric (1,3-diaxial interactions are reduced in
the morpholine ring compared with piperidine) and electronic effects (oxygen atom pulls
none bonding electrons of nitrogen). Figure 4 illustrates these effects.
EXPERIMENTAL
All reactions were carried out in an efficient hood. The starting materials were
purchased from Merck and Fluka chemical companies. Melting points were determined
Figure 3 Dipolar canonical structures in amides and thioamides.

ONE-POT SYNTHESIS OF SYMMETRICAL DTC PODANDS
1277
Figure 4 Favored forms for 4a–i
.
with a Branstead Electrothermal model 9200 and are uncorrected. IR spectra were recorded
on a Perkin Elmer RX 1 Fourier transform infrared spectrometer. The 1H NMR and 13C NMR
spectra were recorded in DMSO-d6 and CDCl3 on Bruker Avance 300-MHz spectrometers.
Elemental analyses were carried out by a Perkin Elmer 2400 series II CHN/O analyzer.
Typical Experimental Procedure
Starting Materials. Compounds 2a, b: To a solution of the appropriate diamine
1a-c (Scheme 1) (10 mmol) and triethylamine (22 mmol) in acetone (10 mL), was added
chloroacetyl chloride (22 mmol) in acetone (5 mL) dropwise and stirred for 2 h at room
temperature. After completion of the reaction (TLC), the solvent evaporated to afford a
precipitate, which was recrystallized from ethanol to give pure dichlorodiamide (DCD)
(2a–c).
Compounds 4a–c: To a mixture of CS2, 0.42 mL (7 mmol) and amine (7 mmol) in
water (20 mL) was added 4 (3 mmol). After 14 h, the precipitate was filtrated and washed
with acetone to give podands 4a–i. Figures S 1–S 7 (Supplemental Materials) show the 1H
NMR and 13C NMR spectra of sample podands.
N,Nꢀ-bis(2-chloroacetamide)-1,3-diaminobenzene (2a): Yield 96%, mp 221–
223 ◦C; IR (KBr): 3271, 3220, 3091, 1670, 1612, 1233, 1217 cm−1; 1H NMR (300 MHz,
DMSO-d6); δ 4.23 (s, 4H), 7.23–7.33 (m, 3H), 7.94 (s, 1H), 10.35 (s, br, 2H) ppm; 13C
NMR (75 MHz, DMSO-d6); δ 43.6, 110.2, 114.8, 129.2, 138.9, 164.7 ppm; Anal. Calcd.
for C10H10Cl2N2O2: C, 46.00; H, 3.86; N, 10.73; Found: C, 45.91; H, 3.80; N, 10.82.
◦ N,Nꢀ-bis(2-chloroacetamide)-2,6-diaminopyridine (2b): Yield 80%, mp 150–
153 C; IR (KBr): 3386, 3365, 3111, 1686, 1589, 1458, 1312, 1243, 1154, 784 cm−1
;
1H NMR (300 MHz, DMSO); δ 4.37 (s, 4H), 7.73–7.83 (m, 3H), 10.44 (s, br, 2H) ppm;
13C NMR (75 MHz, DMSO); δ 43.5, 109.5, 140.6, 149.8, 165.5 ppm; Anal. Calcd. for
C9H9Cl2N3O2: C, 41.24; H, 3.46; N, 16.03; Found: C, 40.91; H, 3.37; N, 16.18.
N,Nꢀ-Bis(2-chloroacetamide)-2,2ꢀ-diaminodiphenylsulfide (2c): Quantitative
◦
yield, mp 152–153 C; IR (KBr): 3925, 3263, 3176, 1669, 1590, 1579, 1537, 1436, 768,
659 cm−1; H NMR (300 MHz, CDCl3); δ 4.17 (s, 4H), 7.09–7.15 (t, 2H, J = 7.8 Hz),
1
7.23–7.26 (d, 2H, J = 9 Hz), 7.33–7.38 (t, 2H, J = 7.8 Hz), 8.13–8.16 (d, 2H, J = 9 Hz),

1278
A. SHOCKRAVI ET AL.
8.98 (s, 2H, exchanged with D2O) ppm; 13C NMR (75 MHz, CDCl3); δ 43.1, 122.6, 124.1,
126.1, 129.4, 132.7, 136.4, 164.2 ppm; Anal. Calcd. for C16H14Cl2N2O2S: C, 52.04; H,
3.82; N, 7.59; Found: C, 52.31; H, 3.84; N, 7.53.
N,Nꢀ-bis(1-oxoethyl
diethylamine-2-carbamodithioate)-1,3-diaminobenzene
(4a): Yield 77%, viscose liquid; IR (KBr): 3278, 3215, 3082, 2975, 1670, 1609, 1546,
1270, 1202 cm−1; 1H NMR (300 MHz, CDCl3); δ 1.19–1.25 (m, 12H), 3.67 (q, J = 7, 4H),
3.95 (q, J = 6.7, 4H), 4.16 (s, 4H), 7.12–7.36 (m, 3H), 7.76 (s, 1H), 9.2 (s, 2H) ppm; 13C
NMR (75 MHz, CDCl3); δ 11.4, 12.4, 40.5, 47.3, 50.6, 111.2, 115.7, 129.2, 138.3, 167.2,
193.9 ppm; Anal. Calcd. for C20H30N4O2S4: C, 49.35; H, 6.21; N, 11.51; Found: C, 49.52;
H, 6.33; N, 10.4.
N,Nꢀ-bis(1-oxoethyl piperidine-2-carbamodithioate)-1,3-diaminobenzene (4b):
Yield 92%, mp 153–155 ◦C; IR (KBr): 3287, 3232, 3064, 2943, 1700, 1608, 1244,
1
1232 cm−1; H NMR (300 MHz, CDCl3); δ 1.71 (s, br, 12H), 3.89 (s, br, 4H), 4.22
(s, 4H), 4.29 (s, 4H), 7.18–7.32 (m, 3H), 7.64 (s, 1H), 9.09 (s, br, 2H) ppm; 13C NMR
(75 MHz, CDCl3); δ 23.9, 25.4, 25.9, 40.8, 51.8, 54.1, 111.0, 115.6, 129.2, 138.3, 167.1,
193.9 ppm; Anal. Calcd. for C22H30N4O2S4: C, 51.73; H, 5.92; N, 10.97; found: C, 52.01;
H, 5.84; N, 10.88.
N,Nꢀ-bis(1-oxoethyl morpholine-2-carbamodithioate)-1,3-diaminobenzene (4c):
◦
Yield 91%, mp 180–181.5 C; IR (KBr): 3282, 3231, 2958, 2899, 1658, 1605, 1268,
1225 cm−1; 1H NMR (300 MHz, CDCl3); δ 3.81 (s, br, 8H), 3.98 (s, br, 4H), 4.24 (s, 4H),
4.38 (s, 4H), 7.26–7.33 (m, 3H), 7.68(q, J = 1.8, 1H), 8.89 (s, 2H) ppm; 13C NMR (75 MHz,
CDCl3); δ 40.1, 50.8, 52.5, 65.8, 66.4, 111.1, 115.8, 129.4, 138.2, 166.7, 196.1 ppm; Anal.
Calcd. for C20H26N4O4S4: C, 46.67; H, 5.09; N, 10.89; Found: C, 46.91; H, 5.23; N, 11.02.
N,Nꢀ-bis(1-oxoethyl
diethylamine-2-carbamodithioate)-2,6-diaminopyridine
◦
(4d): Yield 87%, mp 186–187 C; IR (KBr): 3241, 3036, 2977, 1700, 1665, 1583, 1271,
1
1202 cm−1; H NMR (300 MHz, CDCl3); δ 1.29–1.36 (m, 12H), 3.79 (q, J = 7.1, 4H),
4.06 (q, J = 7.1, 4H), 4.25 (s, 4H), 7.65 (t, J = 8, 1H), 7.84 (d, J = 7.9, 2H), 9.02 (s,
2H) ppm; 13C NMR (75 MHz, CDCl3); δ 11.5, 12.5, 40.7, 47.3, 50.6, 109.7, 140.4, 149.4,
167.1, 193.7 ppm; Anal. Calcd. for C19H29N5O2S4: C, 46.79; H, 5.99; N, 14.36; Found:
C, 46.68; H, 5.89; N, 14.02.
N,Nꢀ-bis(1-oxoethyl piperidine-2-carbamodithioate)-2,6-diaminopyridine (4e):
Yield 91%, mp 220 ◦C; IR (KBr): 3286, 2939, 2855, 1706, 1584, 1507, 1242, 1230 cm−1
;
1H NMR (300 MHz, CDCl3); δ 1.73 (s, br, 12H), 3.92 (s, br, 4H), 4.27 (s, 4H), 4.30 (s, br,
4H), 7.65 (t, J = 8.0, 1H), 7.85 (d, J = 8.1, 2H), 8.96 (s, 2H) ppm; 13C NMR (75 MHz,
CDCl3); δ 24.1, 25.4, 26.1, 40.7, 51.9, 54.1, 109.8, 140.4, 149.4, 167.1, 193.5 ppm; Anal.
Calcd. for C21H29N5O2S4: C, 49.29; H, 5.71; N, 13.69; Found: C, 49.02; H, 5.68; N, 13.74.
N,Nꢀ-bis(1-oxoethyl morpholine-2-carbamodithioate)-2,6-diaminopyridine (4f):
◦
Yield 91%, mp 217–218.5 C; IR (potassium bromide): 3246, 3106, 2963, 1700, 1585,
1449, 1235, 1115 cm−1; 1H NMR (300 MHz, CDCl3); δ 3.79 (s, 8H), 3.98 (s, br, 4H), 4.27
(s, 4H), 4.35 (s, br, 4H), 7.67 (t, J = 8.0, 1H), 7.86 (d, J = 7.9, 2H), 8.86 (s, 2H), 8.86
(s, 2H); 13C NMR (75 MHz, CDCl3); δ 40.5, 50.7, 52.3, 66.3, 66.2, 109.9, 140.6, 149.2,
166.5, 195.6 ppm; Anal. Calcd. for C19H25N5O4S4: C, 44.25; H, 4.89; N, 13.58; Found: C,
44.37; H, 4.94; N, 13.45.
N,Nꢀ-Bis(1-oxoethyl diethylamine-2-carbamodithioate)-2,2ꢀ-diaminodiphenyl-
sulfide (4g): Yield 92%, mp 83–84.5 ◦C; IR (KBr): 3295, 2976, 1688, 1578, 1516, 1492,
1
1202, 1271 cm−1; H NMR (300 MHz, CDCl3); δ 1.18–1.36 (m, 12H), 3.70 (q, J = 7.1,
4H), 3.93 (q, J = 7.0, 4H), 4.27 (s, 4H), 6.99 (t, J = 7.3, 2H), 7.08 (d, J = 7.1, 2H), 7.26
(t, J = 7.1, 2H), 8.16 (d, J = 8.0, 2H), 9.18 (s, 2H); 13C NMR (75 MHz, CDCl3); δ 11.4,

ONE-POT SYNTHESIS OF SYMMETRICAL DTC PODANDS
1279
12.5, 40.6, 47.1, 50.5, 122.3, 124.1, 125.3, 128.7, 132.3, 137.6, 167.0, 192.9 ppm; Anal.
Calcd. for C26H34N4O2S5: C, 52.49; H, 5.78; N, 9.42; Found: C, 52.58; H, 5.78; N, 9.36.
N,Nꢀ-Bis(1-oxoethyl piperid◦ine-2-carbamodithioate)-2,2ꢀ-diaminodiphenylsul-
fide (4h): Yield 91%, mp 171–173 C; IR (KBr): 3292, 2942, 2917, 1675, 1578, 1521,
1
1430, 1243, 1224 cm−1; H NMR (300 MHz, CDCl3); δ 1.65 (s, 12H), 3.82 (s, b, 4H),
4.19 (s, br, 4H), 4.30 (s, 4H), 6.98 (t, J = 7.4, 2H), 7.08 (d, J = 6.6, 2H), 7.28(t, J = 7.6,
2H), 8.16 (d, J = 8.1, 2H), 9.14 (s, 2H) ppm; 13C NMR (75 MHz, CDCl3); δ 24.0, 24.2,
25.4, 40.7, 51.7, 54.1, 122.5, 125.4, 128.8, 132.3, 137.6, 167.0, 192.9 ppm; Anal. Calcd.
for C28H34N4O2S5: C, 54.34; H, 5.54; N, 9.05; Found: C, 54.48; H, 5.63; N, 9.11.
N,Nꢀ-Bis(1-oxoethyl morpholine-2-carbamodithioate)-2,2ꢀ-diaminodiphenyl-
sulfide (4i): Yield 85%, mp 248–249 ◦C; IR (KBr): 3265, 1663, 1578, 1433, 1268,
1113 cm−1; 1H NMR (300 MHz, CDCl3); δ 3.70 (m, 8H), 3.91 (s, br, 4H), 4.24 (s, b, 4H),
4.30 (s, 4H), 7.01–7.10 (m, 4H), 7.30 (t, J = 8.2, 2H), 8.15 (d, J = 8.0, 2H), 9.02 (s, 2H);
13C NMR (75 MHz, CDCl3); δ 40.4, 51.2, 53.4, 66.1, 66.1, 120.5, 122.8, 125.6, 128.9,
132.25, 166.6, 196.8 ppm; Anal. Calcd. for C29H30N4O4S5: C, 50.14; H, 4.85; N, 9.00;
Found: C, 50.02; H, 4.78; N, 9.8.
REFERENCES
1. Cesur, O. N.; Guner, H.; Uzun, M.; Kiraz, M.; Kaya, D. Farmaco 1995, 50, 361-364.
2. Gunay, N. S.; Capan, G.; Ulusoy, N.; Ergenc, N.; Otuk, G.; Kaya, D. Farmaco 1999, 54, 826-831.
3. Farghaly, A. O.; Moharram, A. M. Boll. Chim. Farmaceutico 1999, 138, 280-289.
4. Xu, L. Z.; Jiao, V.; Zhang, S. S.; Kuang, S. P. Bull. Korean Chem. Soc. 2002, 23, 1699-1701.
5. Ozkirimli, S.; Apak, T. I.; Kiraz, M.; Yegenoglu, Y. Arch. Pharm. Res. 2005, 28, 1213-1218.
6. Schonenberger, V. H.; Lippert, P. Pharmazie 1972, 27, 139-145.
7. Capan, G.; Ergenc, N.; Buyuktimkin, S.; Yulug, N. Sci. Pharm. 1993, 61, 243-250.
8. Chourasia, M. R.; Tyagi, D. Indian J. Phy. Nat. Sci. 1999, 15, 15-21.
9. Imamura, V.; Ohtake, N.; Jona, H.; Shimizu, A.; Moriya, M.; Sato, H.; Sugimoto, Y.; Ikeura,
C., Iyonaga, H.; Nakano, M.; Nagano, R.; Abe, S.; Yamada, K.; Hashizume, T.; Morishima, H.
Bioorg. Med. Chem. 2001, 9, 1571-1578.
10. Scozzafava, A.; Mastrolorenzo, V.; Supuran, C. T. Bioorg. Med. Chem. Lett. 2000, 10, 1887-1891.
11. Cao, S. L.; Feng, Y. P.; Jiang, Y. Y.; Liu, S. Y.; Ding, G. Y.; Li, R. T. Bioorg. Med. Chem. Lett.
2005, 15, 1915-1917.
12. Hogrth, G.; Rainford-Brent, E. J. C.; Richards, I. Inorg. Chim. Acta. 2009, 362, 1361-1364.
13. Burke, J. T. R.; Bajwa, B. S.; Jacobsen, A. E.; Rice, K. C.; Streaty, R. A. J. Med. Chem. 1984,
27, 1570-1574.
14. Tilles, H. J. Am. Chem. Soc. 1959, 81, 714.
15. Walter, W.; Bode, K. D. Angew. Chem., Int. Ed. Engl. 1967, 6, 281-293.
16. (a) Dunn, A. D.; Rudorf, W. D. Carbon Disulphide in Organic Chemistry, Ellis Howard: Chich-
ester, UK, 1989, 226 pp; (b) Garin, J.; Melandz, E.; Merchain, F. L.; Tejero, T.; Urid, S.;
Ayestaron, J. Synthesis 1991, 147-151. (c) Degani, I.; Fochi, R. Synthesis 1978, 365-368.
17. Yan, V.; Chen, V. Synth. Commun. 1999, 29, 2875-2880.
18. Chen, Z. C.; Jin, Y. Y.; Stang, V. J. Org. Chem. 1987, 52, 4117-4118.
19. (a) Azizi, N.; Aryanasab, F.; Torkian, L.; Ziyaei-Halimehjani, A.; Saidi, M. R. J. Org. Chem.
2006, 71, 3634-3635; (b) Ziyaei-Halimehjani, A.; Marjani, K.; Ashouri, A. Green Chem. 2010,
12, 1306-1310.
20. Beers, W. H.; Reich, E. Nature 1970, 228, 917-922.
21. Stewart, W. E.; Siddal, T. H. Chem. Rev. 1970, 70, 517-551.
22. Wiberg, K. B.; Rablen, P. R.; Rush, D. J.; Keith, T. A. J. Am. Chem. Soc. 1995, 117, 4261-4270.
23. Vassilev, N. G.; Dimitrov, V. S. J. Mol. Struct. 1999, 484, 39-47.

1280
A. SHOCKRAVI ET AL.
24. Cox, C.; Lectka, T. Acc. Chem. Res. 2000, 33, 849-858.
25. Kang, Y. K.; Park, H. S. J. Mol. Struct. (Theochem.) 2004, 676, 171-176.
26. Holloway, C. E.; Gitlitz, M. H. Can. J. Chem. 1967, 45, 2659-2663.
27. Gayathri Dew, K. R.; Manogaran, S.; Sathyanarayana, D. N. Phosphorus Sulfur Silicon 1981,
11, 47-54.
28. Modarresi-Alam, A. R.; Najafi, P.; Rostamizadeh, M.; Keykha, H.; Bijanzadeh, H. R.; Kleinpeter,
E. J. Org. Chem. 2007, 72, 2208-2211.
29. Yamagami, C. Y.; Takao, N.; Takeuchi, V. Aust. J. Chem. 1986, 39, 457.
30. Cox, C.; Lectka, T. J. Org. Chem. 1998, 63, 2426-2427.
31. Rablen, P. R. J. Org. Chem. 2000, 65, 7930-7937.
32. Basso, E. A.; Pontes, R. M. J. Mol. Struct. (Theochem) 2002, 594, 199-206.
33. Deetz, M. J.; Forbes, C. C.; Jonas, M., Malerich, J. P.; Smith, B. D.; Wiest, O. J. Org. Chem.
2002, 67, 3949-3952.
34. Smith, B. D.; Goodenough-Lashua, D. M.; D’Souza, C. J. E., Norton, K. J.; Schmidt, L. M.;
Tung, J. C. Tetrahedron Lett. 2004, 45, 2747-2750.
35. Wiberg, K. B.; Rablen, P. R.; Rush, D. J.; Keith, T. A. J. Am. Chem. Soc. 1995, 117, 4261-4270.
36. (a) Shockravi, A.; Kamali, M.; Halimehjani, A.; Jafari, R. J. Heterocycl. Chem. (in press);
(b) Shockravi, A.; Kamali, M.; Sorkhei, F.; Jafari, R. Heteroatom. Chem. 2011, 22, 659-668.
37. Modarresi-Alam, A. R.; Amirazizi, H.; Bagheri, H.; Bijanzadeh, H. R.; Kleinpeter, E. J. Org.
Chem. 2009, 74, 4740-4746.
38. Wiberg, K. B.; Rush, D. J. J. Am. Chem. Soc. 2001, 123, 2038-2046.