Reactions of 4-benzoyl-5-phenylamino-2,3-dihydrothiophene-2,3-dione and diaminomaleonitrile in the presence of alcohols as reactant and solvent

Article abstract of DOI:10.1080/17415993.2017.1307983

The one-pot synthesis of a novel class of 5-(2-alkoxy-2-phenyl-1-N-phenylthiocarbamoylethenyl)-6-oxo-1,6-dihydropyrazine-2,3-dicarbonitriles (2a–o) is achieved in moderate to good yields by the sequential reaction between 4-benzoyl-5-phenylamino-2,3-dihyd

Full text of DOI:10.1080/17415993.2017.1307983

Journal of Sulfur Chemistry
ISSN: 1741-5993 (Print) 1741-6000 (Online) Journal homepage: http://www.tandfonline.com/loi/gsrp20
Reactions of 4-benzoyl-5-phenylamino-2,3-
dihydrothiophene-2,3-dione and
diaminomaleonitrile in the presence of alcohols as
reactant and solvent
Maryam Moloudi, Hassan Kabirifard, Raihaneh Kabirifard & Mona
Mahdikhani
To cite this article: Maryam Moloudi, Hassan Kabirifard, Raihaneh Kabirifard & Mona
Mahdikhani (2017): Reactions of 4-benzoyl-5-phenylamino-2,3-dihydrothiophene-2,3-dione
and diaminomaleonitrile in the presence of alcohols as reactant and solvent, Journal of Sulfur
Chemistry, DOI: 10.1080/17415993.2017.1307983
To link to this article: http://dx.doi.org/10.1080/17415993.2017.1307983
Published online: 03 Apr 2017.
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Date: 03 April 2017, At: 10:14

JOURNAL OF SULFUR CHEMISTRY, 2017
http://dx.doi.org/10.1080/17415993.2017.1307983
Reactions of 4-benzoyl-5-phenylamino-2,3-
dihydrothiophene-2,3-dione and diaminomaleonitrile in the
presence of alcohols as reactant and solvent
Maryam Moloudi, Hassan Kabirifard , Raihaneh Kabirifard and Mona Mahdikhani
Department of Chemistry, Islamic Azad University, North Tehran Branch, Tehran, Iran
ABSTRACT
ARTICLE HISTORY
Received 29 January 2017
Accepted 14 March 2017
The one-pot synthesis of a novel class of 5-(2-alkoxy-2-phenyl-1-N-
phenylthiocarbamoylethenyl)-6-oxo-1,6-dihydropyrazine-2,3-
dicarbonitriles (2a–o) is achieved in moderate to good yields
by the sequential reaction between 4-benzoyl-5-phenylamino-2,3-
dihydrothiophene-2,3-dione, diaminomaleonitrile and alcohols.
KEYWORDS
Multi-component reactions;
pyrazine-2,3-dicarbonitrile;
thiophene-2,3-dione;
diaminomaleonitrile; alcohol
1. Introduction
Pyrazines are important flavor components in food [1], and show interesting anticancer
[1–4] and antituberculosis [1,5–8] activities, and apply in microbial metabolism [9] and as
μ-opioid receptor antagonists [10], and also pyrazine-2,3-dicarbonitriles display varying
degrees of herbicidal activity [11]. Diaminomaleonitrile (DAMN), a tetramer of hydrogen
cyanide and a weakly basic diamine with similar reactivity to o-phenylenediamine, is an
important precursor for the synthesis of pyrazine-2,3-dicarbonitriles [12]. The conden-
sation with 1,2-diketones proceeds at room temperature or by warming for a short time
[12,13]. The reaction of 4-acylated-5-substituted furan-2,3-dione in benzene at reflux for
the synthesis of pyrazine-2,3-dicarbonitriles was reported [14]. The aim of this investi-
gation was the synthesis of new structures bearing pyrazine-2,3-dicarbonitrile moieties.
Herein, we report a simple synthetic method for the preparation of some diazine deriva-
tives from 4-benzoyl-5-phenylamino-2,3-dihydrothiophene-2,3-dione (1) and DAMN in
alcohols (Scheme 1).
CONTACT Hassan Kabirifard
h_kabirifard@iau-tnb.ac.ir
Supplemental data for this article can be accessed here. http://dx.doi.org/10.1080/17415993.2017.1307983
© 2017 Informa UK Limited, trading as Taylor & Francis Group

2
M. MOLOUDI ET AL.
Scheme 1. Three-component coupling of 4-benzoyl-5-phenylamino-2,3-dihydrothiophene-2,3-dione
(1), diaminomaleonitrile, and alcohols.
2. Results and discussion
Reaction of the thiophene-2,3-dione (1) with DAMN in alcohols as a reactant and solvent
at room temperature for 1–3 h gave the pyrazine-2,3-dicarbonitrile derivatives (2a–o) (see
Scheme 1). The products were obtained in moderate yields for unsaturated alcohols and
for t-butyl alcohol and in excellent yields for saturated alcohols as shown in Table 1.
The structures of compounds 2a–o were apparent from their mass spectra, which dis-
played, in each case, the molecular ion peak at the appropriate m/z value. The mass spectra
of the some products exhibited fairly weak molecular ion peaks. The IR, 1H NMR and 13
C
NMR spectroscopic data were in agreement with the proposed structures. The IR spectra of
=
2a–o revealed the characteristic absorption bands of C≡N, amide C O, thioamide C–N,
Table 1. Synthesis of 5-(2-alkoxy-2-phenyl-1-N-phenylthiocarbamoylethenyl)-6-oxo-1,6-
dihydropyrazine-2,3-dicarbonitrile (2a–o).
Entry
R
Product
Yield (%)a
1
2
3
4
5
6
7
8
CH3
CH3CH2
CH3CH2CH2
(CH3)2CH
CH3CH2CH2CH2
CH3CH2(CH3)CH
(CH3)2CHCH2
(CH3)3CH
(CH3)2CHCH2CH2
HOCH2CH2
HOCH2CH2CH2CH2
CH2 CHCH2
PhCH2
2-C4H3OCH2
C6H11
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
2o
89
70
86
72
79
62
70
44
64
68
66
55
37
50
31
9
10
11
12
13
14
15
=
aIsolated yield.

JOURNAL OF SULFUR CHEMISTRY
3
Scheme 2. Proposed mechanism for the one-pot synthesis of pyrazine-2,3-dicarbonitrile (2).
=
NH, C S, and ether C–O–C (asy and sy) groups at 2246–2230, 1749–1719, 1552–1534,
1366–1360, 1184–1169, 1219–1209 and 1139–1078 cm−1, respectively. Their 13C NMR
spectra also showed signals at δ 52.95–74.27, 118.10–122.08, 146.20–147.10, 161.35–162.85
and 185.33–188.50 ppm due to the carbons of the ether C–O, 2C≡N, C5 N, amide C O
=
=
1
=
and thioamide C S. In the H NMR spectra of 2a–o, we had observed two set of multi-
plet signals for aliphatic and aromatic protons and two broad singlet at δ 11.00–12.14 and
13.79–14.10 ppm for the amidic and thioamidic NH protons.
Carbon atoms C–2, C–3 and C–5 in compound 1 are electrophilic sites that can exhibit
different reactivities depending on the structures of the nucleophiles and reaction condi-
tions [15]. The DAMN cyclizes by nucleophilic attack on the α-ketothioesteric fragment
(C–2 and C–3) of 1, then nucleophilic attack of the alcohols to ketonic carbonyl group of
intermediate 3 produce pyrazine-2,3-dicarbonitrile derivatives 2 (see Scheme 2).
3. Conclusion
We have synthesized new pyrazine-2,3-dicarbonitrile derivatives 2a–o using one-pot reac-
tions. The simple experimental and workup conditions of the presented reactions are
combined with high yields of products.
4. Experimental
4.1. General
The chemicals were purchased from Merck and used without further purification. Melting
points were measured with an Electrothermal 9100 apparatus and are uncorrected. Ele-
mental analyses were performed using a Heraeus CHN–O-Rapid analyzer. These results
agree favorably with the calculated values. Infrared spectra were measured from KBr disk
using a Thermo Nicolet 8700 FT-IR spectrometer and frequencies were reported in cm−1
.
1H NMR and 13C NMR spectra were recorded on a Bruker DRX-300 AVANCE at 300, 500

4
M. MOLOUDI ET AL.
and 75, 125 MHz instrument using tetramethylsilane as the internal standard and DMSO-
d6 or CDCl3 as the solvent. Chemical shifts and coupling constants were reported in ppm
and Hz, respectively. Thin-layer chromatography (TLC) was performed on ‘Silufol-UV
254’ plates. Mass spectra were obtained by using an Agilent HP 5973 mass spectrometer
operating at an ionization potential of 70 eV.
4.2. Material
Ethyl 2,4-dioxo-4-phenylbutanoate was prepared from diethyl oxalate (10 mmol) and ace-
tophenone (10 mmol) in the presence of sodium ethoxide (10 mmol) using of ethanol
(30 ml) as the solvent [16]. 4-Benzoyl-5-phenylamino-2,3-dihydrothiophene-2,3-dione (1)
was obtained by careful addition of phenyl isothiocyanate (10 mmol) to benzoylpyruvate
in KOH (10 mmol) and dimethylformamide (20 mL) with stirring at room temperature for
24 h [15].
4.3. General procedure for the synthesis of pyrazine-2,3-dicarbonitriles 2a–o
A mixture of 1 (0.309 g, 1.0 mmol) and 2,3-diaminomaleonitrile (0.108 g, 1.0 mmol) in the
corresponding alcohols (10 mL) was stirred at room temperature for 1–3 h. The progress
of the reaction was monitored by TLC (eluent AcOEt/hexane 4:1). The solvent was evap-
orated, the residue was recrystallized from ethanol for 2a–i and methanol:hexane (9:1)
for 2l–o, and dried. For derivatives 2j,k, the solution was poured into H2O (10 mL), the
precipitate formed, which was filtered and was crystallized from ethanol:H2O (4:1).
4.3.1. 5-(2-Methoxy-2-phenyl-1-N-phenylthiocarbamoylethenyl)-6-oxo-1,6-
dihydropyrazine-2,3-dicarbonitrile (2a)
Orange crystal; yield: 0.37 g (89%); m.p.: 232–234°C. IR (KBr): ν¯ = 3441, 3250 (NH),
=
=
3020 (CH, aromatic), 2977 (CH, aliphatic), 2240 (CN), 1748 (C O, amide), 1605 (C C),
−1
=
1573 (NH), 1540, 1365, 1169 (C–N, NH, C S, thioamide), 1214, 1124 (C–O–C) cm
.
3
1H NMR (DMSO-d6): δ = 3.93 (3H, s, CH3–O), 7.28 (1H, t, JHH = 7.3 Hz, CHpara of
Ph–NH), 7.45 (2H, t, 3JHH = 7.3 Hz, 2CHmeta of Ph–NH), 7.52–7.95 (7H, m, 2Ph), 12.12,
13.82 (2H, 2br.s, 2NH). 13C NMR (DMSO-d6): δ = 52.95 (CH3–O), 114.23 ( C), 118.96,
=
121.46 (2CN), 122.83, 126.41, 126.88, 128.74, 128.86, 129.06 (10C, 2Ph), 130.70 (Cipso
=
of Ph–C C), 139.46 (Cipso of Ph–NH), 146.44 (C5), 148.43 (C3), 149.93 (C2), 151.10
+
=
=
=
(O–C ), 163.24 (C O, amide), 188.28 (C S) ppm. EI-MS: m/z (%) = 413 (M , 5), 411
(23), 380 (3), 319 (7), 220 (27), 193 (6), 165 (14), 135 (27), 93 (100), 77 (93), 44 (70). Anal.
Calcd for C23H15N5O2S (413.45): C, 63.91%; H, 3.66%; N, 16.94%; found: C, 63.85%; H,
3.78%; N, 16.81%.
4.3.2. 5-(2-Ethoxy-2-phenyl-1-N-phenylthiocarbamoylethenyl)-6-oxo-1,6-
dihydropyrazine-2,3-dicarbonitrile (2b)
Orange crystal; yield: 0.30 g (70%); m.p.: 238–240°C. IR (KBr): ν¯ = 3513 (NH), 3040 (CH,
=
=
aromatic), 2977 (CH, aliphatic), 2240 (CN), 1732 (C O, amide), 1601 (C C), 1572 (NH),
1
1539, 1362, 1181 (C–N, NH, C S, thioamide), 1217, 1123 (C–O–C) cm−1. H NMR
=
(DMSO-d6): δ = 1.53 (3H, t, 3JHH = 7.2 Hz, CH3), 4.56 (2H, q, 3JHH = 7.2 Hz, CH2–O),
3
3
7.26 (1H, t, JHH = 7.6 Hz, CHpara of Ph–NH), 7.42 (2H, t, JHH =7.6 Hz, 2CHmeta of

JOURNAL OF SULFUR CHEMISTRY
5
Ph–NH), 7.50–8.04 (7H, m, 2Ph), 11.49, 11.91 (2H, 2br.s, 2NH). 13C NMR (DMSO-d6):
=
δ = 18.43 (CH3), 63.27 (CH2–O), 113.36 ( C), 118.10, 120.80 (2CN), 122.85, 126.39,
=
126.75, 128.63, 128.72, 129.92 (10C, 2Ph), 131.09 (Cipso of Ph–C C), 139.17 (Cipso of
=
=
Ph–NH), 146.50 (C5), 148.91 (C3), 149.26 (C2),+151.10 (O–C ), 162.80 (C O, amide),
=
185.33 (C S) ppm. EI-MS: m/z (%) = 427 (M , 17), 394 (20), 295 (13), 247 (10), 220
(37), 193 (13), 165 (15), 135 (49), 93 (100), 77 (93), 44 (40). Anal. Calcd for C23H17N5O2S
(427.48): C, 64.62%; H, 4.01%; N, 16.38%; found: C, 64.75%; H, 4.15%; N, 16.47%.
4.3.3. 5-(2-n-Propoxy-2-phenyl-1-N-phenylthiocarbamoylethenyl)-6-oxo-1,6-
dihydropyrazine-2,3-dicarbonitrile (2c)
Dark orange crystal; yield: 0.38 g (86%); m.p.: 236–238°C. IR (KBr): ν¯ = 3510 (NH), 2977
=
=
(CH, aliphatic), 2240 (CN), 1732 (C O, amide), 1601 (C C), 1573 (NH), 1540, 1362, 1181
(C–N, NH, C S, thioamide), 1218, 1124 (C–O–C) cm−1. 1H NMR (DMSO-d6): δ = 0.93
=
3
3
(3H, t, JHH = 7.4 Hz, CH3), 1.59 (2H, m, CH2), 4.40 (2H, t, JHH = 7.4 Hz, CH2-O),
3
3
7.28 (1H, t, JHH = 7.8 Hz, CHpara of Ph–NH), 7.45 (2H, t, JHH = 7.8 Hz, 2CHmeta of
Ph–NH), 7.51–7.94 (7H, m, 2Ph), 12.10, 13.79 (2H, 2br.s, 2NH). 13C NMR (DMSO-
=
d6): δ = 10.36 (CH3), 21.59 (CH2), 67.29 (CH2–O), 114.30 ( C), 118.65, 121.45 (2CN),
=
122.83, 126.29, 126.90, 128.65, 128.69, 129.12 (10C, 2Ph), 130.51 (Cipso of Ph–C C),
=
139.48 (Cipso of Ph–NH), 147.10 (C5), 148.53 (C3), 149.89 (C2+), 151.10 (O–C ), 162.80
=
=
(C O, amide), 188.25 (C S) ppm. EI-MS: m/z (%) = 441 (M , 1), 426 (3), 394 (4), 220
(23), 165 (5), 135 (100), 93 (73), 77 (71), 51 (24). Anal. Calcd for C24H19N5O2S (441.50):
C, 65.29%; H, 4.34%; N, 15.86%; found: C, 65.17%; H, 4.19%; N, 15.98%.
4.3.4. 5-(2-Isopropoxy-2-phenyl-1-N-phenylthiocarbamoylethenyl)-6-oxo-1,6-
dihydropyrazine-2,3-dicarbonitrile (2d)
Brownish yellow powder; yield: 0.32 g (72%); m.p.: 206–208°C. IR (KBr): ν¯ = 3440, 3282
=
(NH), 3026 (CH, aromatic), 2978 (CH, aliphatic), 2240 (CN), 1728 (C O, amide), 1602
=
=
(C C), 1573 (NH), 1542, 1360, 1184 (C–N, NH, C S, thioamide), 1218, 1104 (C–O–C)
cm−1. H NMR (DMSO-d6): δ = 1.38 (6H, d, JHH = 6.0 Hz, 2CH3), 5.23 (1H, m,
1
3
3
3
CH–O), 7.29 (1H, t, JHH = 7.4 Hz, CHpara of Ph–NH), 7.46 (2H, t, JHH = 7.4 Hz,
2CHmeta of Ph–NH), 7.53–7.94 (7H, m, 2Ph), 12.14, 13.82 (2H, 2br.s, 2NH). 13C NMR
=
(DMSO-d6): δ = 21.61 (2CH3), 69.70 (CH–O), 114.29 ( C), 118.65, 121.44 (2CN),
=
122.93, 126.40, 126.80, 128.70, 128.78, 129.18 (10C, 2Ph), 130.66 (Cipso of Ph–C C),
=
139.45 (Cipso of Ph–NH), 146.20 (C5), 148.90 (C3), 149.81 (C+2), 150.90 (O–C ), 162.35
=
=
(C O, amide), 188.13 (C S) ppm. EI-MS: m/z (%) = 441 (M , 3), 408 (3), 220 (27), 142
(19), 93 (100), 77 (49), 43 (23). Anal. Calcd for C24H19N5O2S (441.50): C, 65.29%; H,
4.34%; N, 15.86%; found: C, 65.41%; H, 4.22%; N, 15.75%.
4.3.5. 5-(2-n-Butoxy-2-phenyl-1-N-phenylthiocarbamoylethenyl)-6-oxo-1,6-
dihydropyrazine-2,3-dicarbonitrile (2e)
Brownish yellow powder; yield: 0.36 g (79%); m.p.: 208–210°C. IR (KBr): ν¯ = 3436, 3260
=
(NH), 3015 (CH, aromatic), 2925 (CH, aliphatic), 2240 (CN), 1732 (C O, amide), 1603
=
=
(C C), 1575 (NH), 1542, 1366, 1182 (C–N, NH, C S, thioamide), 1219, 1122 (C–O–C)
cm−1. H NMR (DMSO-d6): δ = 0.91 (3H, t, JHH = 7.2 Hz, CH3), 1.41, 1.72 (4H,
2 m, 2CH2), 4.36 (2H, t, 3JHH = 7.2 Hz, CH2-O), 7.29 (1H, t, 3JHH = 7.3 Hz, CHpara of
Ph–NH), 7.45 (2H, t, 3JHH = 7.3 Hz, 2CHmeta of Ph–NH), 7.51–7.94 (7H, m, 2Ph), 12.12,
1
3

6
M. MOLOUDI ET AL.
13.82 (2H, 2br.s, 2NH). 13C NMR (DMSO-d6): δ = 13.59 (CH3), 18.66, 30.17 (2CH2),
=
65.50 (CH2–O), 114.26 ( C), 118.74, 121.47 (2CN), 122.91, 126.38, 126.80, 128.68, 128.78,
=
129.16 (10C, 2Ph), 130.66 (Cipso of Ph–C C), 139.45 (Cipso of Ph–NH), 146.99 (C5),
=
=
=
148.70 (C3), 149.79 (C2), 151.10 (O–C ), 162.86 (C O, amide), 188.13 (C S) ppm. EI-
MS: m/z (%) = 455 (M+, 1), 439 (5), 347 (6), 220 (20), 142 (21), 93 (100), 77 (23), 41 (50).
Anal. Calcd for C25H21N5O2S (455.53): C, 65.92%; H, 4.65%; N, 15.37%; found: C, 65.80%;
H, 4.73%; N, 15.57%.
4.3.6. 5-(2-Sec-butoxy-2-phenyl-1-N-phenylthiocarbamoylethenyl)-6-oxo-1,6-
dihydropyrazine-2,3-dicarbonitrile (2f)
Dark Orange powder; yield: 0.28 g (62%); m.p.: 230–232°C. IR (KBr): ν¯ = 3440, 3261
=
(NH), 3017 (CH, aromatic), 2958 (CH, aliphatic), 2240 (CN), 1732 (C O, amide),
=
=
1603 (C C), 1575 (NH), 1542, 1365, 1182 (C–N, NH, C S, thioamide), 1218, 1122
(C–O–C) cm−1. 1H NMR (DMSO-d6): δ = 0.97 (3H, t, 3JHH = 7.5 Hz, CH3), 1.39 (3H, d,
3JHH = 6.2 Hz, CH3), 1.76 (2H, m, CH2), 5.14 (1H, m, CH–O), 7.10 (1H, t, 3JHH = 7.7 Hz,
3
CHpara of Ph–NH), 7.37 (2H, t, JHH = 7.7 Hz, 2CHmeta of Ph–NH), 7.53–7.60 (3H,
3
3
m, Ph), 7.69 (2H, d, JHH = 7.7 Hz, 2CHortho of Ph–NH), 7.92 (2H, d, JHH = 7.8 Hz,
2CHortho of Ph–C C), 11.00, 14.10 (2H, 2br.s, 2NH). 13C NMR (DMSO-d6): δ = 9.69,
=
=
19.36 (2CH3), 28.37 (CH2), 74.27 (CH–O), 114.10 ( C), 119.02, 122.08 (2CN), 123.69,
=
127.77, 128.11, 129.03, 129.13, 130.48 (10C, 2Ph), 130.92 (Cipso of Ph–C C), 138.80 (Cipso
=
=
of Ph–NH), 143.58 (C5), 147.94 (C3), 148.30 (C2), 150.54 (O–C ), 161.85 (C O, amide),
+
=
185.50 (C S) ppm. EI-MS: m/z (%) = 455 (M , 1), 319 (4), 220 (21), 142 (13), 93 (100),
77 (38), 41 (27). Anal. Calcd for C25H21N5O2S (455.53): C, 65.92%; H, 4.65%; N, 15.37%;
found: C, 65.79%; H, 4.76%; N, 15.51%.
4.3.7. 5-(2-Isobutoxy-2-phenyl-1-N-phenylthiocarbamoylethenyl)-6-oxo-1,6-
dihydropyrazine-2,3-dicarbonitrile (2g)
Brownish yellow powder; yield: 0.32 g (70%); m.p.: 200–202°C. IR (KBr): ν¯ = 3260 (NH),
=
=
3014 (CH, aromatic), 2965 (CH, aliphatic), 2245 (CN), 1733 (C O, amide), 1603 (C C),
−1
=
1575 (NH), 1542, 1365, 1182 (C–N, NH, C S, thioamide), 1218, 1122 (C–O–C) cm
.
1H NMR (DMSO-d6): δ = 0.96 (6H, d, JHH = 6.7 Hz, 2CH3), 2.05 (1H, m, CH), 4.15
(2H, d, 3JHH = 6.7 Hz, CH2–O), 7.28 (1H, t, 3JHH = 7.6 Hz, CHpara of Ph–NH), 7.44 (2H,
br.t, 3JHH = 7.6 Hz, 2CHmeta of Ph–NH), 7.51–7.93 (7H, m, 2Ph), 12.10 13.79 (2H, 2br.s,
2NH). 13C NMR (DMSO-d6): δ = 18.80 (2CH3), 27.32 (CH2), 71.35 (CH2-O), 114.18
3
=
( C), 118.68, 121.46 (2CN), 122.92, 126.32, 126.80, 128.64, 128.70, 129.06 (10C, 2Ph),
=
130.59 (Cipso of Ph–C C), 139.41 (Cipso of Ph—NH), 146.90 (C5), 148.72 (C3), 149.81
=
=
=
(C2), 151.10 (O–C ), 162.81 (C O, amide), 188.17 (C S) ppm. EI-MS: m/z (%) = 455
(M+, 2), 394 (5), 295 (5), 220 (19), 134 (34), 93 (100), 77 (92), 41 (60). Anal. Calcd for
C25H21N5O2S (455.53): C, 65.92%; H, 4.65%; N, 15.37%; found: C, 66.08%; H, 4.54%; N,
15.58%.
4.3.8. 5-(2-Tert-butoxy-2-phenyl-1-N-phenylthiocarbamoylethenyl)-6-oxo-1,6-
dihydropyrazine-2,3-dicarbonitrile (2h)
Dark orange crystal; yield: 0.20 g (44%); m.p.: 206–208°C. IR (KBr): ν¯ = 3439, 3258 (NH),
=
=
3017 (CH, aromatic), 2957 (CH, aliphatic), 2240 (CN), 1732 (C O, amide), 1600 (C C),
1575 (NH), 1537, 1365, 1181 (C–N, NH, C S, thioamide), 1217, 1139 (C–O–C) cm−1. 1H
=

JOURNAL OF SULFUR CHEMISTRY
7
NMR (DMSO-d6): δ = 1.31 (9H, s, 3CH3), 7.28 (1H, t, 3JHH = 7.6 Hz, CHpara of Ph–NH),
3
7.45 (2H, t, JHH = 7.6 Hz, 2CHmeta of Ph–NH), 7.55–7.95 (7H, m, 2Ph), 12.12, 13.80
(2H, 2br.s, 2NH). 13C NMR (DMSO-d6): δ = 25.61 (3CH3), 64.70 (C–O), 114.34 ( C),
=
118.55, 121.47 (2CN), 122.83, 126.27, 126.70, 128.29, 128.65, 129.14 (10C, 2Ph), 130.47
=
(Cipso of Ph–C C), 139.50 (Cipso of Ph–NH), 147.10 (C5), 148.45 (C3), 149.91 (C+2), 151.10
=
=
=
(O–C ), 162.81 (C O, amide), 188.27 (C S) ppm. EI-MS: m/z (%) = 455 (M , 4), 394
(44), 295 (20), 220 (39), 165 (28), 93 (100), 77 (96), 51 (26). Anal. Calcd for C25H21N5O2S
(455.53): C, 65.92%; H, 4.65%; N, 15.37%; found: C, 65.73%; H, 4.77%; N, 15.21%.
4.3.9. 5-(2-Isopentoxy-2-phenyl-1-N-phenylthiocarbamoylethenyl)-6-oxo-1,6-
dihydropyrazine-2,3-dicarbonitrile (2i)
Orange yellow crystal; yield: 0.30 g (64%); m.p.: 226–228°C. IR (KBr): ν¯ = 3278 (NH),
=
=
3027 (CH, aromatic), 2978 (CH, aliphatic), 2240 (CN), 1728 (C O, amide), 1602 (C C),
1572 (NH), 1542, 1360, 1183 (C–N, NH, C S, thioamide), 1218, 1104 (C–O–C) cm−1. 1H
=
NMR (DMSO-d6): δ = 0.91 (6H, d, 3JHH = 6.5 Hz, 2CH3), 1.63 (2H, q, 3JHH = 6.7 Hz,
CH2), 1.74 (1H, m, CH), 4.39 (2H, t, 3JHH = 6.7 Hz, CH2–O), 7.28 (1H, t, 3JHH = 7.4 Hz,
CHpara of Ph–NH), 7.44 (2H, t, 3JHH = 7.4 Hz, 2CHmeta of Ph–NH), 7.56–7.94 (7H, m,
2Ph), 12.11, 13.80 (2H, 2br.s, 2NH). 13C NMR (DMSO-d6): δ = 22.32 (2CH3), 24.58 (CH),
36.80 (CH2), 64.27 (CH2–O), 114.26 (=C), 118.75, 121.47 (2CN), 122.91, 126.38, 126.80,
=
128.67, 128.78, 129.15 (10C, 2Ph), 130.66 (Cipso of Ph–C C), 139.45 (Cipso of Ph–NH),
=
=
=
147.00 (C5), 148.67 (C3), 149.76 (C2), 150.60 (O–C ), 162.82 (C O, amide), 188.13 (C S)
ppm. EI-MS: m/z (%) = 469 (M+, 1), 456 (59), 377 (13), 322 (9), 221 (9), 181 (78), 142 (17),
93 (100), 77 (65), 43 (27). Anal. Calcd for C26H23N5O2S (469.56): C, 66.50%; H, 4.94%; N,
14.91%; found: C, 66.32%; H, 5.17%; N, 14.70%.
4.3.10. 5-(2-(2-Hydroxyethoxy)-2-phenyl-1-N-phenylthiocarbamoylethenyl)-6-oxo-
1,6-dihydropyrazine-2,3-dicarbonitrile (2j)
Orange crystal; yield: 0.30 g (68%); m.p.: 257–259°C. IR (KBr): ν¯ = 3450 (NH), 3250 (OH),
=
=
2965 (CH, aliphatic), 2240 (CN), 1740 (C O, amide), 1607 (C C), 1573 (NH), 1542, 1363,
1184 (C–N, NH, C S, thioamide), 1218, 1078 (C–O–C), 1032 (C–OH) cm−1. 1H NMR
=
3
3
(DMSO-d6): δ = 3.73 (2H, br.t, JHH = 4.9 Hz, CH2OH), 4.38 (2H, t, JHH = 4.9 Hz,
CH2–O), 4.95 (1H, br.t, OH), 7.28 (1H, t, 3JHH = 7.6 Hz, CHpara of Ph–NH), 7.44 (2H,
3
t, JHH = 7.6 Hz, 2CHmeta of Ph–NH), 7.56–7.93 (7H, m, 2Ph), 12.13, 13.81 (2H, 2br.s,
2NH). 13C NMR (DMSO-d6): δ = 62.74 (CH2OH), 67.41 (CH2-O), 114.10 ( C), 118.91,
=
122.04 (2CN), 122.81, 126.16, 127.72, 128.60, 128.92, 129.16 (10C, 2Ph), 130.42 (Cipso
=
of Ph–C C), 139.51 (Cipso of Ph–NH), 146.50 (C5), 148.60 (C3), 149.92 (C2), 150.90
+
=
=
=
(O–C ), 162.67 (C O, amide), 188.50 (C S) ppm. EI-MS: m/z (%) = 443 (M , 1), 322
(6), 220 (15), 165 (9), 93 (93), 77 (51), 44 (100). Anal. Calcd for C23H17N5O3S (443.48): C,
62.29%; H, 3.86%; N, 15.79%; found: C, 62.05%; H, 4.08%; N, 15.48%.
4.3.11. 5-(2-(4-Hydroxybutoxy)-2-phenyl-1-N-phenylthiocarbamoylethenyl)-6-oxo-
1,6-dihydropyrazine-2,3-dicarbonitrile (2k)
Yellow orange crystal; yield: 0.31 g (66%); m.p.: 228–230°C. IR (KBr): ν¯ = 3507 (NH),
=
=
3405 (OH), 2975 (CH, aliphatic), 2242 (CN), 1736 (C O, amide), 1604 (C C), 1574
=
(NH), 1547, 1364, 1178 (C–N, NH, C S, thioamide), 1219, 1126 (C–O–C), 1040
(C–OH) cm−1. H NMR (DMSO-d6): δ = 1.53, 1.78 (4H, 2 m, 2CH2), 3.43 (2H, br.t,
1

8
M. MOLOUDI ET AL.
3
3JHH = 6.5 Hz, CH2OH), 4.37 (2H, t, JHH = 6.5 Hz, CH2–O), 4.44 (1H, br.t, OH),
3
3
7.28 (1H, t, JHH = 7.5 Hz, CHpara of Ph–NH), 7.45 (2H, t, JHH = 7.5 Hz, 2CHmeta of
Ph–NH), 7.57–7.93 (7H, m, 2Ph), 12.12, 13.82 (2H, 2br.s, 2NH). 13C NMR (DMSO-
=
d6): δ = 24.99, 28.80 (2CH2), 60.21 (CH2OH), 65.77 (CH2–O), 114.14 ( C), 118.68,
121.46 (2CN), 122.92, 126.34, 126.76, 128.67, 128.74, 129.14 (10C, 2Ph), 130.64 (Cipso
=
of Ph–C C), 139.44 (Cipso of Ph–NH), 146.52 (C5), 148.65 (C3), 149.81 (C2), 150.89
=
=
=
(O–C ), 162.85 (C O, amide), 188.17 (C S) ppm. EI-MS: m/z (%) = 316 (8), 261 (5),
191 (5), 147 (5), 97 (18), 57 (100), 43 (63). Anal. Calcd for C25H21N5O3S (471.53): C,
63.68%; H, 4.49%; N, 14.85%; found: C, 63.41%; H, 4.75%; N, 14.69%.
4.3.12. 5-(2-Allyloxy-2-phenyl-1-N-phenylthiocarbamoylethenyl)-6-oxo-1,6-
dihydropyrazine-2,3-dicarbonitrile (2l)
Yellow orange powder; yield: 0.24 g (55%); m.p.: 145–147°C. IR (KBr): ν¯ = 3475, 3297
=
=
(NH), 3080 (CH, aromatic), 2240 (CN), 1749 (C O, amide), 1643, 1602 (C C),
=
1583 (NH), 1552, 1362, 1176 (C–N, NH, C S, thioamide), 1213, 1091 (C–O–C)
cm−1. H NMR (DMSO-d6): δ = 4.89 (2H, d, JHH = 5.7 Hz, CH2–O), 5.29 (1H, d,
1
3
3
3
=
=
=
Jcis = 10.5 Hz, CH), 5.45 (1H, d, Jtrans = 17.2 Hz, CH), 6.06 (1H, m, CH), 7.28
3
3
(1H, t, JHH = 7.4 Hz, CHpara of Ph–NH), 7.44 (2H, t, JHH = 7.4 Hz, 2CHmeta of
Ph–NH), 7.51–7.94 (7H, m, 2Ph), 12.10, 13.81 (2H, 2br.s, 2NH). 13C NMR (DMSO-d6):
=
=
δ = 66.08 (CH2–O), 114.18 ( C), 118.64 ( CH2), 118.78, 121.46 (2CN), 122.85, 126.34,
=
=
126.83, 128.64, 128.75, 129.09 (10C, 2Ph), 130.63 (Cipso of Ph–C C), 132.19 ( CH),
=
139.42 (Cipso of Ph–NH), 146.86 (C5), 148.44 (C3), 149.83 (C2), 150.50 (O–C ), 162.36
=
=
(C O, amide), 188.12 (C S) ppm. EI-MS: m/z (%) = 438 (3), 406 (10), 322 (5), 220 (14),
142 (22), 109 (10), 93 (90), 77 (98), 41 (100). Anal. Calcd for C24H17N5O2S (439.49): C,
65.59%; H, 3.90%; N, 15.94%; found: C, 65.88%; H, 4.11%; N, 16.19%.
4.3.13. 5-(2-Benzyloxy-2-phenyl-1-N-phenylthiocarbamoylethenyl)-6-oxo-1,6-
dihydropyrazine-2,3-dicarbonitrile (2m)
Dark orange powder; yield: 0.18 g (37%); m.p.: 198–200°C. IR (KBr): ν¯ = 3255 (NH), 3009
=
=
(CH, aromatic), 2246 (CN), 1731 (C O, amide), 1662, 1601 (C C), 1574 (NH), 1541,
1364, 1175 (C–N, NH, C S, thioamide), 1216, 1120 (C–O–C) cm−1. 1H NMR (DMSO-
=
3
d6): δ = 5.44 (2H, s, CH2O), 7.27 (1H, t, JHH = 7.7 Hz, CHpara of Ph–NH), 7.30–7.40
3
(5H, m, Ph–CH2), 7.42 (2H, t, JHH = 7.7 Hz, 2CHmeta of Ph–NH), 7.49–7.93 (7H, m,
2Ph), 12.11, 13.80 (2H, 2br.s, 2NH). 13C NMR (DMSO-d6): δ = 67.04 (CH2-O), 114.37
=
( C), 118.83, 121.54 (2CN), 122.91, 126.19, 126.37, 126.57, 127.98, 128.25, 128.48, 128.60,
=
129.22 (15C, 3Ph), 130.38 (Cipso of Ph–C C), 139.50 (Cipso of Ph–NH), 142.47 (Cipso of
=
=
Ph–CH2), 146.60 (C5), 148.13 (C3), 149.87 (C2)+, 150.10 (O–C ), 162.66 (C O, amide),
=
188.22 (C S) ppm. EI-MS: m/z (%) = 489 (M , 1), 220 (5), 124 (7), 91 (100), 77 (21),
65 (25), 45 (15). Anal. Calcd for C28H19N5O2S (489.55): C, 68.70%; H, 3.91%; N, 14.31%;
found: C, 68.49%; H, 4.20%; N, 14.58%.
4.3.14. 5-(2-Fufuryloxy-2-phenyl-1-N-phenylthiocarbamoylethenyl)-6-oxo-1,6-
dihydropyrazine-2,3-dicarbonitrile (2n)
Dark orange powder; yield: 0.24 g (50%); m.p.: 164–166°C. IR (KBr): ν¯ = 3438, 3295 (NH),
=
=
3031 (CH, aromatic), 2240 (CN), 1719 (C O, amide), 1640, 1602 (C C), 1573 (NH), 1534,

JOURNAL OF SULFUR CHEMISTRY
9
1360, 1174 (C–N, NH, C S, thioamide), 1209, 1121 (C–O–C) cm−1. 1H NMR (DMSO-
d6): δ = 5.41 (2H, s, CH2O), 6.50 (1H, br.s, CHfurfuryl), 6.65 (1H, d, JHH = 2.9 Hz,
=
3
=
=CHfurfuryl), 7.28 (1H, t, 3JHH =7.4 Hz, CHpara of Ph–NH), 7.44 (2H, t, 3JHH = 7.4 Hz,
=
2CHmeta of Ph–NH), 7.51–7.60 (3H, m, Ph), 7.72 (1H, s, CHfurfuryl), 7.87–7.94 (4H, m,
2Ph), 12.10, 13.81 (2H, 2br.s, 2NH). 13C NMR (DMSO-d6): δ = 59.06 (CH2–O), 106.80
=
ꢀ
ꢀ
(C4 ), 110.45 (C3 ), 114.14 ( C), 118.76, 121.45 (2CN), 122.94, 126.35, 126.83, 128.57,
=
128.75, 129.12 (10C, 2Ph), 130.64 (Cipso of Ph–C C), 139.38 (Cipso of Ph–NH), 144.00
(C5 ), 146.99 (C5), 148.84 (C3), 149.80 (C2), 149.89 (O–C ), 152.10 (C2 ), 162.30 (C O,
=
=
ꢀ
ꢀ
=
amide), 188.08 (C S) ppm. EI-MS: m/z (%) = 354 (8), 322 (20), 220 (39), 165 (13), 93
(42), 77 (83), 44 (100). Anal. Calcd for C26H17N5O3S (479.51): C, 65.12%; H, 3.57%; N,
14.61%; found: C, 64.88%; H, 3.34%; N, 14.79%.
4.3.15. 5-(2-Cyclohexyloxy-2-phenyl-1-N-phenylthiocarbamoylethenyl)-6-oxo-1,6-
dihydropyrazine-2,3-dicarbonitrile (2o)
Dark orange powder; yield: 0.15 g (31%); m.p.: 214–216°C. IR (KBr): n¯ = 3250 (NH),
=
=
3013 (CH, aromatic), 2930 (CH, aliphatic), 2245 (CN), 1728 (C O, amide), 1601 (C C),
−1
=
1573 (NH), 1543, 1364, 1182 (C–N, NH, C S, thioamide), 1219, 1121 (C–O–C) cm
.
1H NMR (DMSO-d6): δ = 1.35–1.96 (10H, m, 5CH2), 4.99 (1H, br.m, CH–O), 7.28 (1H,
3
3
t, JHH = 7.5 Hz, CHpara of Ph–NH), 7.44 (2H, t, JHH = 7.5 Hz, 2CHmeta of Ph–NH),
7.52–7.92 (7H, m, 2Ph), 12.13, 13.79 (2H, 2br.s, 2NH). 13C NMR (DMSO-d6): δ = 23.23
=
(2CH2), 24.81 (CH2), 31.05 (2CH2), 74.14 (CH–O), 114.38 ( C), 118.30, 121.49 (2CN),
=
122.90, 126.23, 127.39, 128.58, 128.64, 129.23 (10C, 2Ph), 130.40 (Cipso of Ph–C C),
=
139.49 (Cipso of Ph–NH), 146.90 (C5), 148.71 (C3), 149.79 (C2), 150.10 (O–C ), 162.23
+
=
=
(C O, amide), 188.10 (C S) ppm. EI-MS: m/z (%) = 481 (M , 2), 380 (5), 322 (7), 220
(15), 142 (14), 93 (100), 77 (70), 41 (63). Anal. Calcd for C27H23N5O2S (481.57): C, 67.34%;
H, 4.81%; N, 14.54%; found: C, 67.18%; H, 5.03%; N, 14.69%.
Disclosure statement
No potential conflict of interest was reported by the authors.
ORCID
Hassan Kabirifard http://orcid.org/0000-0003-2680-8051
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