Synthesis and crystal structure of (Z)-ethyl 5-(phenylamino)-3- (phenylimino)-3H-1,2-dithiole-4-carboxylate

Article abstract of DOI:10.1080/00397911.2010.518280

The compound (Z)-ethyl 5-(phenylamino)-3-(phenylimino)-3H-1,2-dithiole-4- carboxylate 3 has been synthesized by the reaction of ethylacetoacetate 1 and phenylisothiocyanate 2. Its structure has been established by 1H NMR, 13C NMR, infrared, mass spectra, and X-ray crystallography.

Full text of DOI:10.1080/00397911.2010.518280

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Synthesis and Crystal Structure
of (Z)-Ethyl 5-(phenylamino)-3-
(phenylimino)-3H-1,2-dithiole-4-
carboxylate
a
a
b
Mehtab Parveen , Sayed H. Mehdi , Mohammad N. Siddiqui
&
b
Mohammed B. Fettouhi
a
Department of Chemistry , Aligarh Muslim University , Aligarh ,
UP , India
b
Department of Chemistry , King Fahd University of Petroleum and
Minerals , Dahran , Saudi Arabai
Accepted author version posted online: 30 Jun 2011.Published
online: 08 Jun 2011.
To cite this article: Mehtab Parveen , Sayed H. Mehdi , Mohammad N. Siddiqui & Mohammed B.
Fettouhi (2011) Synthesis and Crystal Structure of (Z)-Ethyl 5-(phenylamino)-3-(phenylimino)-3H-1,2-
dithiole-4-carboxylate, Synthetic Communications: An International Journal for Rapid Communication
of Synthetic Organic Chemistry, 41:23, 3469-3476, DOI: 10.1080/00397911.2010.518280
To link to this article: http://dx.doi.org/10.1080/00397911.2010.518280
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1
Synthetic Communications , 41: 3469–3476, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.518280
SYNTHESIS AND CRYSTAL STRUCTURE OF (Z)-ETHYL
5
1
-(PHENYLAMINO)-3-(PHENYLIMINO)-3H-
,2-DITHIOLE-4-CARBOXYLATE
1
1
Mehtab Parveen, Sayed H. Mehdi, Mohammad N. Siddiqui,
2
2
and Mohammed B. Fettouhi
1
Department of Chemistry, Aligarh Muslim University, Aligarh, UP, India
Department of Chemistry, King Fahd University of Petroleum and Minerals,
Dahran, Saudi Arabai
2
GRAPHICAL ABSTRACT
Abstract The compound (Z)-ethyl 5-(phenylamino)-3-(phenylimino)-3H-1,2-dithiole-4-
carboxylate 3 has been synthesized by the reaction of ethylacetoacetate 1 and phenylisothio-
1
13
cyanate 2. Its structure has been established by H NMR, C NMR, infrared, mass spec-
tra, and x-ray crystallography.
Keywords Crystal structure; synthesis; (Z)-ethyl 5-(phenylamino)-3-(phenylimino)-3H-1,
2
-dithiole-4-carboxylate
INTRODUCTION
Dithioles are used as additives to motor oils to inhibit metal corrosion.
[
1,2]
[
3]
Some dithioles exhibit pronounced physiological activity and are important
[
reagents in the synthesis of various organo-sulfur compounds. Methods for the
4]
[
preparation of substituted dithioles have been developed. In the 1990s, it was
4]
Received May 6, 2010.
Address correspondence to Mehtab Parveen, Department of Chemistry, Aligarh Muslim
University, Aligarh 202002, UP, India. E-mail: mehtab.organic2009@gmail.com
3
469

3470
M. PARVEEN ET AL.
[
5,6]
discovered that dithiole derivatives may be used as anticancer drugs.
They also
inhibit the replication of HIV viruses. 1,2-Dithiole derivatives have a gene-
[7]
[
8,9]
repairing function and are capable of repairing damaged DNA.
They prevent
the formation of tumors because of their unique electronic structure and thus induce
cancer resistance in the human body. There has been great interest in the antican-
[
cer activity of dithiole derivatives and related compounds.
[10]
11]
Keeping in mind the medicinal importance of dithiole derivatives, we planned
to synthesize the dithiole moiety by reaction with ethylacetoacetate 1 and phenyli-
sothiocyanate 2 in the presence of phase-transfer catalyst cetyltrimethyl ammonium
bromide (CTAB) and Na CO . The reaction was carried out in different molar ratios
2
3
of ethylacetoacetate and phenyl isothiocyanate. In the molar ratio 1:1, the reaction
[
12]
gave a known compound, carbamothioate, along with some unresolved products.
1
13
Its structure was established by infrared (IR), H NMR, C NMR, and mass spectro-
graphic (MS) spectra and confirmed by x-ray crystallography. When the reaction
was repeated under similar conditions in molar ratios 1:2 and 1:3, some unresolved
products were obtained. Finally, the reaction was carried out in the molar ratio 1:4
and furnished a novel crystalline compound named (Z)-ethyl 5-(phenylamino)-3-
(
phenylimino)-3H-1,2-dithiole-4-carboxylate 3, which was characterized on the basis
1
of modern spectroscopic techniques: IR, H NMR, and MS. Its molecular structure
was further confirmed by single-crystal x-ray analysis.
RESULTS AND DISCUSSION
A mixture of ethylacetoacetate 1 and phenylisothiocyanate 2 in molar ratio 1:4
was taken in benzene. A catalytic quantity of phase-transfer catalyst CTAB and
sodium carbonate as a base were also added along with 1–2 drops of water. The
reaction mixture was then heated on water bath for 18 h. After the usual workup
followed by crystallization with chloroform–alcohol, it afforded compound 3, mp
ꢀ
1
55 C.
The elemental analysis of the compound 3 corresponded to the molecular for-
mula C H N O S . Its IR spectrum exhibits strong absorption bands at 3476, indi-
1
8
16
2
2 2
cating the presence of a N-H group. Other bands observed were 1682 (C=O),
ꢁ
1
388 cm (C-N), etc. The H NMR spectrum of the compound displayed a singlet
1
1
at d 9.6, which was assigned to N-H protons. A triplet and quartet at d 1.48 and 4.44
were attributed to methyl and methylene groups respectively. Two multiplets cen-
tered at d 7.6 and 7.8 were ascribed to two benzene rings in the compound. The struc-
1
3
[13a–c]
ture was further suggested by its C NMR spectrum,
68 assigned to carbonyl carbon of ester. C-3, C-4, and C-5 carbons of the dithiole
ring were observed at d 153.1, 99, and 144.1, respectively. Imine and amine phenyl
which showed a peak at d
1

SYNTHESIS OF DITHIOLE DERIVATIVE
3471
Scheme 1. Scheme of mass fragmentation of compound 3.
carbons appeared at d 117.0–149. Peaks at d 62.1 and 14.2 were assigned to methyl-
ene and methyl carbons respectively. The structure was further supported by its mass
þ
spectrum, which gave molecular ion peak [M ] at m=z 356; other notable peaks were
observed at m=z 279, 265, 187, 92, 91, 77, 65, 51, etc. The mass fragmentation pattern
of compound 3 is given in Scheme 1.
The formation of compound 3 under the condition is proposed in Scheme 2.
Crystal Structure Determination of Compound 3
The structure of compound 3 was also conformed by x-ray analysis. The dis-
ulfide five-membered ring is essentially planar. The S–S bond distance is 2.0642
˚ ˚ ˚
[
(11) A, and the two C–S bond distances are 1.755 (3) A and 1.816 (3) A. These values
are in the range known for cyclic disulfides.
14,15]
The compound adopts the Z con-
figurations around the imine (C=N) bond, and the conformation of the amino group
is stabilized by an intramolecular hydrogen bonding interaction characterized by a
˚
N –H —O distance of 1.912 A. The torsion angles between the heterocycle and
2
1
2

3472
M. PARVEEN ET AL.
Scheme 2. Probable mechanism for formation of the title compound.
ꢀ
ꢀ
the two phenyl rings are 61.5(5) and ꢁ113.0(4) for the amine and imine phenyls
˚
ꢀ
respectively. Selected bond lengths (A) and bond angles ( ) for compound 3 are given
in Tables 1 and 2 and Figure 1.
On the basis of these results, the compound 3 was characterized as (Z)-ethyl-
5-(phenylamino)-3-(phenylimino)-3H-1,2-dithiole-4-carboxylate 3, which is reported
here for the first time.
CONCLUSION
The present report describes the first successful attempt to synthesize novel
Z)-ethyl 5-(phenylamino)-3-(phenylimino)-3H-1,2-dithiole-carboxylate (II) using a
simple synthetic methodology.
(

SYNTHESIS OF DITHIOLE DERIVATIVE
3473
Table 1. Crystallographic data of compound 3
Compound
3
Empirical formula
Formula weight
Crystal color and shape
Crystal size (mm)
Space group
18 16 2 2 2
C H N O S
356.45
Yellow, parallele piped
Triclinic
P-1
297
Temperature (K)
Radiation
˚
Mo Ka (k ¼ 0.71073 A)
ꢁ3
q
calc (g cm
˚
)
1.348
5.7396 (8)
12.2162 (16)
14.1234 (1)
112.120 (2)
97.848 (2)
100.699 (2)
878.0 (2)
2
a (A)
˚
b (A)
˚
c (A)
a ( )
ꢀ
ꢀ
b ( )
ꢀ
c ( )
˚
3
V (A )
Z
ꢁ
1
m (mm )
Transmission coefficient
0.316
0.879–0.975
7749
Measured reflections
Independent reflections (Rint
)
4034 (0.0229)
2765
Observed reflections [I > 2r(I)]
R
R
1
, w R
, w R
2
2r(I)
(all data)
0.0560, 0.1352
0.0849, 0.1463
222
1
2
Number of variables
ꢁ3
˚
dqmin, dqmax (e A
Goodness of fit on F
)
ꢁ0.210, 0.395
1.108
3
EXPERIMENTAL
Instruments and Materials
All melting points were observed on a Kofler hot block and are uncorrected. IR
specta were obtained neat on a Perkin-Elmer 1800 Fourier transform (FT)–IR spec-
ꢁ
1
trophotometer. IR values are given in centimeters . NMR spectra were recorded in
CDCl on a Bruker AV 500 (500 MHz) with (CH ) Si as internal standard, and its
3
3 4
values are given in parts per million (ppm, d). Mass spectra were measured on Jeol
D-300 (E mode) and Jeol S ꢂ 102=DA-6000 (FAB mode) mass spectrophotometers.
1
All reagents and solvents were commercially obtained and of analytical grade. In
x-ray crystallography, a crystal was mounted on a glass fiber. Diffraction data were
recorded on a Bruker-Axs Smart Apex system equipped with a graphite monochro-
˚
matized Mo Ka radiation (k ¼ 0.71073 A). The data were collected using SMART.
The data integration was performed using SAINT. An empirical absorption correc-
tion was carried out using SADABS. The structure was solved with the direct meth-
2
ods and refined by full matrix least square methods based on F , using the structure
determination and graphics package SHELXTL based on SHELX 97. The amine
hydrogen atom was located on a difference Fourier map and refined isotropically.
All other hydrogen atoms were included at calculated positions using a riding model.
Crystallographic data are given in Table 1. Selected bond lengths and angles are

3474
M. PARVEEN ET AL.
Table 2. Bond lengths and bond angles of compound 3
Bond
Value
S1–C5
S1–S2
1.816 (3)
2.0642 (11)
1.755 (3)
1.324 (3)
1.463 (4)
1.220 (4)
1.258 (3)
1.421 (4)
1.341 (4)
1.432 (4)
0.84 (3)
1.468 (4)
1.379 (4)
1.457 (4)
96.64 (10)
94.90 (10)
S2–C6
O1–C3
O1–C2
O2–C3
N1–C5
N1–C7
N2–C6
N2–C13
N2–H1
C3–C4
C4–C6
C4–C5
C5–S1–S2
C6–S2–S1
C3–O1–C2
C5–N1–C7
C6–N2–C13
C6–N2–H1
C13–N2–H1
O2–C3–O1
O2–C3–C4
O1–C3–C4
C6–C4–C5
C6–C4–C3
C5–C4–C3
N1–C5–C4
N1–C5–S1
C4–C5–S1
N2–C6–C4
N2–C6–S2
C4–C6–S2
117.1
119.8
126.3
109
(2)
(2)
(3)
(2)
(2)
(3)
(3)
(3)
(3)
(3)
(3)
(3)
(2)
(2)
(3)
(2)
(2)
124
121.2
123.2
115.5
118.0
118.4
123.6
128.2
120.0
111.8
126.0
115.8
118.1
given in Table 2. Complete bond lengths and bond angles, anisotropic thermal
parameters, and calculated hydrogen coordinates are deposited as supplementary
materials.
Preparation of (Z)-Ethyl 5-(Phenylamino)-3-(phenylimino)-3H-
1,2-dithiole-4-carboxylate 3
A solution of ethylacetoacetate (1.26 ml, 10 mmol) in dry benzene (50 ml) was
refluxed with phenylisothiocyanate (4.76 ml, 10 mmol). A catalytic quantity of
phase-transfer catalyst CTAB (0.073 g, 0.0002 mol) and Na CO (2.12 g, 0.02 mol)
2
3
as a base, along with a catalytic amount of water, were also added. The reaction mix-
ture was heated on water bath for 18 h. After the usual workup in ether and evap-
oration of the solvent, it gave a semisolid, which was purified by column
chromatography (silica gel mesh size 230–400) using benzene–ethylacetate (9:1) as

SYNTHESIS OF DITHIOLE DERIVATIVE
3475
Figure 1. ORTEP diagram showing the conformation for (Z)-ethyl-5-(phenylamino)-3-(phenylimino)-3H-
,2-dithiole-carboxylate.
1
eluting solvent. The fraction obtained was crystallized with CHCl –EtOH to yield a
3
ꢀ
yellow crystalline compound 3. Yield: 150 mg; mp: 155 C. C H N O S (C, 60.65;
1
8
16
þ.
2
2 2
H, 4.52; N, 7.86; O, 8.98; S, 17.99%), MS m=z (rel. int.), 356 [M ] (2.2), 279 (3.1),
1
65 (2.6), 187 (5.6), 92 (7.6), 91 (24.8), 77 (70.5), 65 (30.5), 51 (67.9); H NMR
2
(
500 MHz, CDCl ) d (ppm): 1.48 (3H, t, CH ), 4.44 (2H, q, CH ), 7.60–7.80 (10H,
3
3
3
2
1
m, aromatic protons), 9.60 (1H, s, NH); C NMR (500 MHz, CDCl ) d 168.0
3
(
C=O of ester), 153.1 (C-3 of dithiole ring), 149.0–117 (carbons of amine and imine
phenyl), 62.1 (OCH ), 14.2 (CH ).
3
2
Supplementary Data
The supplementary x-ray data are available from the CCDC, 12 Union Road,
Cambridge CB21EZ, UK, on request, quoting the deposition no. 622413.
ACKNOWLEDGMENTS
We are thankful to Prof. M. Mushfiq for useful discussion and to the chairman
of the Department of Chemistry for providing the necessary facilities.
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