The utility of p-N-succinimidobenzoyl isothiocyanate in synthesis of benzoxazole, quinazoline, pyrimidine, 1,2,4-triazoline, 1,3-thiazolidine, and thiourea derivatives

Article abstract of DOI:10.1080/10426500903127557

Reactions of p-N-succinimidobenzoyl isothiocyanate (1) with different nucleophilic reagents afforded adducts. Simultaneous or subsequent cyclization of these adducts gave access to a variety of different heterocycles, including benzoxazole, quinazoline, pyrimidine, 1,2,4-triazoline, 1,3-thiazolidine and others. The structures of the new products were confirmed by their micro-analytical and spectral data. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426500903127557

This article was downloaded by: [University of Colorado - Health Science Library]
On: 11 October 2014, At: 07:57
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Phosphorus, Sulfur, and Silicon and the
Related Elements
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/gpss20
The Utility of p-N-Succinimidobenzoyl
Isothiocyanate in Synthesis of
Benzoxazole, Quinazoline, Pyrimidine,
1,2,4-Triazoline, 1,3-Thiazolidine, and
Thiourea Derivatives
A. F. Fahmy a , N. Ali a , H. Abdelhamid a , S. Shiba a & M. M.
Hemdan a
a Department of Chemistry , Faculty of Science, Ain Shams
University , Abbasia, Cairo, Egypt
Published online: 03 Jul 2010.
To cite this article: A. F. Fahmy , N. Ali , H. Abdelhamid , S. Shiba & M. M. Hemdan (2010) The Utility
of p-N-Succinimidobenzoyl Isothiocyanate in Synthesis of Benzoxazole, Quinazoline, Pyrimidine, 1,2,4-
Triazoline, 1,3-Thiazolidine, and Thiourea Derivatives, Phosphorus, Sulfur, and Silicon and the Related
Elements, 185:7, 1536-1542, DOI: 10.1080/10426500903127557
To link to this article: http://dx.doi.org/10.1080/10426500903127557
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the
“Content”) contained in the publications on our platform. However, Taylor & Francis,
our agents, and our licensors make no representations or warranties whatsoever as to
the accuracy, completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content
should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims,
proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or
howsoever caused arising directly or indirectly in connection with, in relation to or arising
out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden. Terms &

Conditions of access and use can be found at http://www.tandfonline.com/page/terms-
and-conditions

Phosphorus, Sulfur, and Silicon, 185:1536–1542, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500903127557
THE UTILITY OF p-N-SUCCINIMIDOBENZOYL
ISOTHIOCYANATE IN SYNTHESIS OF BENZOXAZOLE,
QUINAZOLINE, PYRIMIDINE, 1,2,4-TRIAZOLINE,
1,3-THIAZOLIDINE, AND THIOUREA DERIVATIVES
A. F. Fahmy, N. Ali, H. Abdelhamid, S. Shiba,
and M. M. Hemdan
Department of Chemistry, Faculty of Science, Ain Shams University, Abbasia,
Cairo, Egypt
Reactions of p-N-succinimidobenzoyl isothiocyanate (1) with different nucleophilic reagents
afforded adducts. Simultaneous or subsequent cyclization of these adducts gave access to
a variety of different heterocycles, including benzoxazole, quinazoline, pyrimidine, 1,2,4-
triazoline, 1,3-thiazolidine and others. The structures of the new products were confirmed
by their micro-analytical and spectral data.
Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental
file.
Keywords Benzoxazole; pyrimidine; quinazoline; p-N-succinimidobenzoyl isothiocyanate;
thiourea derivatives; 1,2,4-triazoline
INTRODUCTION
Isothiocyanates may serve as versatile building blocks to prepare a wide variety
of nitrogen, sulfur, and oxygen heterocycles1–13 besides thiourea derivatives, which are
reported to exhibit antiviral14 and antibacterial15 activities. In the present investigation a
synthetic procedure has been developed to describe a further application of the title com-
pound 1 in heterocyclic synthesis. Of the heterocyclic systems, benzoxazole, quinazoline,
1,2,4-triazoline, 1,3-thiazolidine, and pyrimidine derivatives were synthesized. Further-
more, they were substituted with N-phenyl pyrrolidine dione moiety in an aim to increase
their biological activities.
RESULTS AND DISCUSSION
The new derivatives were prepared according to the reaction sequences depicted in
Schemes 1 and 2. As shown in Scheme 1, treatment of p-N-succinimidobenzoyl isothio-
cyanate (1) with 2-aminophenol in dry acetone produced thiourea derivative 2. Heating of
Received 15 March 2009; accepted 17 June 2009.
Address correspondence to M. M. Hemdan, Department of Chemistry, Faculty of Science, Ain Shams
University, 11566 Abbasia, Cairo, Egypt. E-mail: mhemdan39@hotmail.com
1536

UTILITY OF p-N-SUCCINIMIDOBENZOYL ISOTHIOCYANATE
1537
RCONCS
1
COOH
OH
CNCH2CONH2
NH
NH
O
2
2
O
S
H
N
H
COOH
HN
N
R
R
R
N
NH
S
O
N
H
S
OH
4
H N
2
O
2
6
fusion
-H2S
Ac2O
O
S
N
O
O
O
NHCOR
N
R
N
R =
O
N
H
3
5
Scheme 1
RCONCS
1
HSCH2COOH
PhNHNH2
Ar-CONHNH2
NH2CH2COOH
H
N
COOH
R
O
NH
S
COOH
R
NH
H
H
N
N
O
S
Ar
S
NH
O
O
12
S
R
10
7a) Ar = C6H5
b) Ar = p-ClC6H4
S
Ac2O
N
NH
PPA
N
S
S
O
O
Ph
R
9
N
NH
N
S
R
R
N
O
Ar
11
8a,b
Scheme 2
compound 2 just above its melting point led to evolution of H2S gas and left a product for-
mulated as benzoxazole derivative 3. Similar treatment of isothiocyanate 1 with anthranilic
acid yielded thiourea derivative 4, which was cyclized to quinazoline derivative 5 upon
heating with acetic anhydride. A further aspect of the reactivity of 1 was exemplified by
its reaction with 2-cyanoacetamide to give pyrimidine derivative 6 in a one-pot reaction.
Formation of compound 6 can be visualized on the basis of addition of an amino group of
cyanoacetamide to the isothiocyanate carbon atom, followed by intramolecular cyclization,
as illustrated in Scheme S1 (available online in the Supplemental Materials).

1538
A. F. FAHMY ET AL.
The structures of compounds 2–6 were proven by their microanalytical and spectral
data. Their IR spectra showed the presence of υ (NH), υ (C O), and υ (C S). Their 1H
NMR spectra displayed signals due to CH2CH2 moiety and aromatic protons signals,
as well as acidic protons signals in the downfield region that were exchangeable with D2O.
Treatment of isothiocyanate 1 with aroyl hydrazine afforded thiourea derivatives 7a,b.
Heating of compounds 7a,b with poly phosphoric acid furnished 1,2,4-triazole derivatives
8a,b. Alternatively, the reaction of 1 with phenyl hydrazine produced 1,2,4-triazole deriva-
tive 9 in a one-pot reaction. Reaction of isothiocyanate 1 with thioglycolic acid yielded an
adduct 10, which upon heating with acetic anhydride easily converted into 1,3-thiazolidine
derivatives 11. Furthermore, reaction of 1 with glycine in the presence of a catalytic amount
of pyridine gave the thiourea derivative 12 in a good yield as shown in Scheme 2.
The structures of compounds 7–12 were elucidated by their microanalytical and
spectral data. Their IR spectra showed the presence of υ (NH) except compound 11, υ
1
(C O), υ (C S), as well as a broad OH band for compound 12. In addition, their H
NMR spectra shed further light on the assigned structures as they displayed signals due to
CH2CH2 and aromatic as well as acidic protons in downfield region. Further proof for
the assigned structures of the synthesized compounds was gained from their MS, which
revealed their molecular ion peaks.
CONCLUSION
Aroyl isothiocyanate is a bifunctional reagent that is capable of participating in a
wide range of addition–cyclization reactions. The strong electron-attracting power of the
aroyl group enhances the reactivity of the adjacent isothiocyanato function and promotes
nucleophilic addition at this center. Simultaneous or subsequent cyclization of adducts
gives access to a variety of five- or six-membered heterocyclic structures.
EXPERIMENTAL
Melting points were determined in open capillary tubes on a Gallenkemp melting
point apparatus and are uncorrected. The infrared spectra were recorded on Perkin-Elmer
2000 FTIR and Maston 1000-FTIR spectrometers. The 1H NMR spectra were measured on
a Jeol (EX-400) spectrometer with chemical shift (δ) expressed in ppm downfield from TMS
as internal standard in DMSO-d6. All acidic protons disappeared by deuterium exchange
(addition of D2O). Mass spectra were determined with a JEOL-JMS, DX 303. Elemental
analysis was determined by CHN Carder-MT-3 Yanaco and Perkin-Elemer 2400 CHN
elemental analyzers. TLC was carried out the monitoring of the progress of all reactions
and homogeneity of the synthesized compounds. TLC was determined using TLC aluminum
sheets silica gel F254 (Merck).
p-N-Succinimidobenzoyl Isothiocyanate (1)
To p-N-succinimido-benzoyl chloride16 (3 mmol) in dry acetone (30 mL), solid
ammonium thiocyanate17 (3 mmol) was added. The reaction mixture was stirred for half
an hour at room temperature. The precipitated ammonium chloride was filtered off to give
a clear yellow solution of p-N-succinimidobenzoyl isothiocyanate (1) in acetone.

UTILITY OF p-N-SUCCINIMIDOBENZOYL ISOTHIOCYANATE
1539
Reactions of Isothiocyanate 1 with the Different Nucleophiles
To a solution of isothiocyanate 1 (3 mmole), each of o-aminophenol, anthranilic acid,
2-cyanoacetamide, benzoyl hydrazine, phenyl hydrazine, thioglycollic acid, or glycine in a
dry acetone (50 mL) was added. A few drops of pyridine were added in the case of glycine.
The mixture was refluxed for 2–3 h (as confirmed by TLC) and cooled to room temperature.
The precipitated solid was filtered off, washed with ethanol, and recrystallized from the
suitable solvent to give the corresponding compounds.
1-(2-Hydroxyphenyl)-3-(p-N-succinimidobenzoyl)thiourea
(2). Yellow
crystals (DMF), 80% yield; mp 220–221◦C; IR (KBr) ν: 3480–2865 (br. OH), 3377, 3277,
1760, 1711, 1657, 1265 cm−1; 1H NMR (DMSO-d6) δ: 2.82 (s, 4, CH2CH2 ), 6.85 (t, 1,
J = 7.8 Hz,), 6.95 (d, 1, J = 8.3 Hz,), 7.09 (t, 1, J = 7.8 Hz,), 7.45 (d, 2, J = 8.30 Hz),
8.07 (d, 2, J = 8.79 Hz), 8.55 (d, 1, J = 7.32 Hz,), 10.25 (s, 1, NH exchangeable), 11.59
(s, 1, NH exchangeable), 12.90 (s, 1, OH exchangeable); MS (70 eV) m/z (%): 369 (M+.,
1), 352 (1), 335 (10), 218 (8), 202 (100), 174 (10), 146 (10), 132 (20), 118 (2); Anal.
Calcd. for C18H15N3O4S (369.39): C, 58.53; H, 4.09; N, 11.38; Found: C, 58.23; H, 3.85;
N, 11.12.
1-(2-Carboxyphenyl)-3-(p-N-succinimidobenzoyl)thiourea
(4). Yellow
crystals (acetic acid), 82% yield; mp 196◦C dec.; IR (KBr) ν: br. 3430–3100, 3260, 1750,
1720, 1710, 1660, 1280 cm−1;1H NMR: (DMSO-d6) δ: 2.81 (s, 4, CH2CH2 ), 4.94
(br. s, 1, NH exchangeable), 7.29–8.56 (m, 8, ArH), 11.17 (br. s, 1, NH exchangeable),
11.40 (br. s, 1, OH exchangeable); MS (70 eV) m/z (%): 353 (M+.-CO2, 1), 319 (1),
202 (50), 218 (25), 174 (5), 162 (50), 137 (30), 132 (10), 119 (100), 92 (70); Anal.
Calcd. for C19H15N3O5S (397.40): C, 57.42; H, 3.80; N, 10.57; Found: C, 57.62; H, 4.00;
N, 10.82.
4-Amino-3-(p-N-succinimidobenzoyl)pyrimidin-6-one-2-thione (6). Col-
orless crystals (ethanol), 78% yield; mp 230–232◦C; IR (KBr) ν: 3368, 3358, 3315, 1776,
1711, 1650, 1287;1H NMR: (DMSO-d6) δ: 2.82 (s, 4, CH2CH2 ), 7.42 (d, 2, J = 8.00 Hz),
7.50 (s, 1, C5 H,), 7.85 (d, 2 J = 8.2 Hz), 8.92 (br. s, 2, NH exchangeable), 11.29 (br, s,
1, NH exchangeable); MS (70 eV) m/z (%): 344 (M+., 3), 311 (17), 285 (24), 202 (66),
174 (100), 146 (58); Anal. Calcd. for C15H12N4O4S (344.34): C, 52.32 H, 3.51; N, 16.27
Found; C, 52.40; H, 3.33; N, 15.99.
1-Benzoyl-4-(p-N-succinimidobenzoyl)thiosemicarbazide (7a). Colorless
crystals (DMF), 86% yield; mp 220–222◦C; IR (KBr) ν: 3350, 3180, 1750, 1719, 1670,
1
1278 cm−1, H NMR: (DMSO-d6) δ: 2.80 (s, 4, CH2CH2 ), 7.42 (d, 2, J = 8.7 Hz,
ArH), 7.56–8.09 (m, 7, Ar H), 9.11 (br.s, 1, NH exchangeable), 10.87 (br, s, 1, NH ex-
changeable), 11.11 (br.s, 1, NH exchangeable); MS (70 eV) m/z (%): 396 (M+., 1), 378
(M+.-H2O, 2), 362 (2), 218 (1), 202 (100), 178 (1), 174 (10), 105 (70), 77 (50); Anal.
Calcd. for C19H16N4O4S (396.42): C, 57.57; H, 4.07; N, 14.13; Found: C, 57.33; H, 4.09;
N, 13.97.
1-(p-Chlorobenzoyl)-4-(p-N-succinimidobenzoyl)thiosemicarbazide
(7b). Colorless crystals (acetic acid), 80% yield; mp 310–312◦C; IR (KBr) ν: 3320, 3200,
1755, 1705, 1665, 1280 cm−1; 1H NMR: (DMSO-d6) δ: 2.80 (s, 4, CH2CH2 ), 7.47 (d,
1, J = 8.8 Hz), 7.50 (d, 1, J = 8.8Hz), 7.62 (d, 2, J = 8.28 Hz), 7.93 (d, 1, J = 8.28 Hz),
8.02 (d, 1, J = 8.28), 8.08 (d, 1, J = 8.28 Hz), 8.23 (d, 1, J = 8.32 Hz), 11.24 (br. s, 1, NH
exchangeable), 11.87 (br. s, 1, NH exchangeable), 12.32 (br. s, 1, NH exchangeable); MS
(70 eV) m/z (%): 432 (M+.+2, 4), 430 (M+., 13), 414 (11), 412 (23), 398 (1), 396 (8), 202
(100), 174 (10), 146 (10); Anal. Calcd. for C19H15ClN4O4S (430.86): C, 52.96; H, 3.51;
N, 13.00; Found: C, 52.74 H, 3.35; N, 12.81.

1540
A. F. FAHMY ET AL.
2-Phenyl-3-(p-N-succinimidophenyl)-2,5-dihydro-1H-1,2,4-triazole-5-thi
one (9). Yellow crystals (DMF), 70% yield; mp 202–203◦C; IR (KBr) ν: 3184, 1780,
1703, 1603, 1295 cm−1;1H NMR (DMSO-d6) δ: 2.81 (s, 4, CH2CH2 ), 7.43–7.49 (m,
3, ArH), 7.56 (t, 2, J = 7.83 Hz), 8.03 (d, 2, J = 7.32 Hz), 8.10 (d, 2, J = 8.28), 14.38 (br.
s, 1, NH exchangeable); MS (70 eV) m/z (%): 350 (M+., 90), 318 (10), 291 (10), 202 (10),
176 (5), 174 (1), 91 (100); Anal. Calcd. for C18H14N4O2S (350.39): C, 61.70; H, 4.03; N,
15.99; Found: C, 61.72; H, 4.15; N, 15.95.
Carboxymethyl N-(p-N-Succinimidobenzoyl)dithiocarbamate (10). Yel-
low crystals (ethanol), 76% yield; mp 213–215◦C; IR (KBr) ν: br. 3700–2700, 1750, 1711,
1
1685, 1270 cm−1; HNMR (DMSO-d6) δ: 2.80 (s, 4, CH2CH2 ), 3.3 (s, 2, S CH2),
7.60 (d, 2, J = 8.32 Hz), 8.10 (d, 2, J = 8.80 Hz), 9.58 (br.s, 1, NH exchangeable), 11.34
(br. s, 1, OH exchangeable); MS (70 eV) m/z (%): 352 (M+., 3), 307 (2), 302 (5), 218 (20),
202 (100), 174 (19), 90 (15); Anal. Calcd. for C14H12N2O5S2 (352.39): C, 47.72; H, 3.43;
N, 7.95; Found: C, 47.66; H, 3.50; N, 8.02.
1-Carboxymethyl-3-(p-N-succinimidobenzoyl)thiourea
(12). Colorless
crystals (ethanol), 88% yield; mp 208–210◦C; IR (KBr) ν: br. 3416–2700, 1765, 1730,
1720, 1660, 1260 cm−1; 1H NMR (DMSO-d6) δ: 2.80 (s, 4, CH2CH2 ), 4.35 (d, 2, J =
5Hz, CH2) 7.43 (d, 2, J = 8.00 Hz), 8.03 (d, 2, J = 8.79 Hz), 9.83 (br. s, 1, NH or SH
exchangeable), 11.10 (br. s, 1, NH exchangeable), 11.59 (br. s, 1, OH exchangeable); MS
(70 eV) m/z (%): 335 (M+., 1), 317 (1), 290 (1), 277 (4), 244 (2), 218 (20), 202 (100), 174
(15), 146 (15), 133 (30);.Anal. Calcd. for C14H13N3O5S (335.34): C, 50.14; H, 3.91; N,
12.53; Found: C, 50.43; H, 4.12; N, 12.23.
General Procedure for the Synthesis of Compounds 5 and 11
Compounds 4 and 10 (2 mmol) were heated with acetic anhydride (20 mL) at 90◦C
for 1 h. Solid product obtained after cooling was filtered and recrystallized from acetic acid
to give yellow crystals of compound 5 or 11, respectively.
3-(p-N-Succinimidobenzoyl)quinazoline-4-one-2-thione (5). 86% yield;
mp 265–266◦C; IR (KBr) ν: 3370, 1760, 1718, 1650, 1285; 1H NMR: (DMSO-d6) δ: 2.80
(s, 4, CH2CH2 ), 7.46 (d, 1, J = 8.75 Hz), 7.55 (t, 1, J = 7.33 Hz), 7.70 (d, 1, J = 7.8
Hz), 7.90 (t, 1, J = 7.32 Hz), 8.08 (d, 2, J = 7.33 Hz), 8.15 (d, 2, J = 8.50 Hz), 12.41 (br.
s, 1, NH exchangeable); MS (70 eV) m/z (%): 379 (M+., 10), 351 (5), 202 (100), 177 (2),
174 (10), 146 (16), (132 (20); Anal. Calcd. for C19H13N3O4S (379.39): C, 60.15; H, 3.45;
N, 11.08; Found: C, 59.82; H, 3.66; N, 10.82.
3-(p-N-Succinimidobenzoyl)-1,3-thiazolidine-4-one-2-thione (11). 73%
1
yield; mp 213–215◦C (ethanol); IR (KBr) ν: 1730, 1719, 1680, 1279 cm−1; H NMR
(DMSO-d6) δ: 2.81 (s, 4, CH2CH2 ), 4.60 (s, 2, SCH2) 7.55 (d, 2, J = 8.32 Hz), 8.21
(d, 2, J = 8.76 Hz); MS (70 eV) m/z (%): 334 (M+., 10), 202 (100), 174 (10), 146 (5), 132
(15), 120 (20), 104 (2); Anal. Calcd. for C14H10N2O4S2 (334.37): C, 50.29; H, 3.01; N,
8.38; Found: C, 50.40; H, 2.99; N, 8.65.
General Procedure for the Synthesis of Compounds 8a and 8b
A solution of compounds 7a or 7b (2 mmol) in glacial acetic acid (30 mL) was
added to polyphosphoric acid (20 mL). The reaction mixture was heated at 150–180◦C for
1 h, then left to cool at room temperature. The precipitated solid obtained after addition of
ice-cold water was filtered off and recrystallized from a suitable solvent.

UTILITY OF p-N-SUCCINIMIDOBENZOYL ISOTHIOCYANATE
1541
3-Phenyl-4-(p-N-succinimidobenzoyl)-4,5-dihydro-1H-1,2,4-triazole-5-thi
one (8a). Colorless crystals (acetic acid), 72% yield; mp 330–333◦C; IR (KBr) ν: 3230,
1
1750, 1720, 1665, 1603, 1280 cm−1; H NMR (DMSO-d6) δ: 2.80 (s, 4, CH2CH2 ),
7.49 (d, 2, J = 8.32 Hz), 7.54–8.13 (m, 5, ArH), 8.23 (d, 2, J = 8.23 Hz), 13.25 (br. s, 1,
NH exchangeable); MS (70 eV) m/z (%): 378 (M+., 20), 350 (15), 202 (100), 174 (10),
146 (10), 132 (20); Anal. Calcd. for C19H14N4O3S (378.40): C, 60.31; H, 3.73; N, 14.81;
Found: C, 59.96; H, 3.90; N, 14.71.
3-(p-Chlorophenyl)-4y-(p-N-succinimidobenzoyl)-4,5-dihydro-1H-1,2,4-
triazole-5-thione (8b). Colorless crystals (DMF), 83% yield; mp 363–365◦C; IR (KBr)
ν: 3261, 1755, 1718, 1660, 1270 cm−1; 1H NMR (DMSO-d6) δ: 2.81 (s, 4, CH2CH2 ),
7.49 (d, 2, J = 8.76, Hz), 7.61(d, 2, J = 8.70 Hz), 8.01 (d, 2, J = 8.32 Hz), 8.23 (d,
2, J = 8.80), 13.29 (br. s, 1, NH exchangeable); MS (70 eV) m/z (%): 414 (M+.+2, 3),
412 (M+., 10), 386 (1), 384 (2), 202 (100), 174 (10), 146 (10), 132 (20); Anal. Calcd.
for C19H13ClN4O3S (412.85): C, 55.28; H, 3.17; N, 13.57; Found: C, 55.21; H, 2.95;
N, 13.37.
2-(p-N-Succinimidobenzamido)-1,3-benzoxazole (3)
Compound 2 (2 mmol) was heated at 220–230◦C. H2S gas was evolved during the
fusion process. After 1 h, H2S evolution was ceased, the reaction mixture was left to cool,
and the solid mass was triturated with ethanol. The solid that separated was collected and
crystallized from ethanol to give pale yellow crystals. 81% yield; IR (KBr) ν: 3232, 1770,
1720, 1650, cm−1;1H NMR (DMSO-d6) δ: 2.81 (s, 4, CH2CH2 ), 6.85 (t, 1, J = 7.90
Hz), 6.70 (d, 1, J = 8.30 Hz), 7.13 (t, 1, J = 7.60 Hz), 7.47 (d, 2, J = 8.10 Hz), 8.07 (d, 2,
J = 8.79), 8.55 (d, 1, J = 7.32 Hz), 11.33 (br. s, 1, NH exchangeable); MS (70 eV) m/z (%):
335 (M+., 13), 218 (8), 202 (100), 174 (10), 146 (16), 132 (34), 118 (9), 109 (20); Anal.
Calcd. for C18H13N3O4 (335.31): C, 64.47; H, 3.91; N, 12.53; Found: C, 64.72; H, 4.02;
N, 12.77.
REFERENCES
1. L. Drobnica, P. Kristian, and J. Augustin, In The Chemistry of Cyanates and Their Thio Deriva-
tives, S. Patai, ed. (John Wiley & Sons, New York, 1977), vol. 2, p. 1003.
2. S. Sharma, Sulfur Rep., 8, 327 (1989).
3. A. K. Mukerjee and R. Ashare, Chem. Rev., 91, 1 (1991).
4. N. A. Nedolya, B. A. Trofimov, and A. Senning, Sulfur Rep., 17, 183 (1996).
5. B. A. Trofimov, J. Heterocycl. Chem., 36, 1469 (1999).
6. G. Sommen, Synlett, 7, 1323 (2004).
7. M. M. Hemdan, A. F. Fahmy, N. F. Ali, E. Hegazi, and A. Abd-Elhaleem, Chinese J. Chem., 25,
388 (2007).
8. M. M. Hemdan and M. M. Elshahawi, J. Chem. Res., 2, 75 (2009).
9. M. Makhloufi-Chebli, M. Hamdi, A. M. S. Silva, O. Duval, and J. Helesbeux, J. Heterocyclic
Chem., 46, 18 (2009).
10. A. Benjelloun, G. Morel, and E. Marchand, Heteroatom Chem., 11(1), 16 (2000).
11. A. F. Sayed Ahmed, N. Aouf, and M. G. Assy, J. Chem. Res. (S), 508 (1998).
12. M. Avalos, R. Babiano, P. Cintas, M. Chavero, F. J. Higes, J. L. Jime´nez, J. C. Palacios, and G.
Silvero, J. Org. Chem., 65(26), 8882 (2000).
13. A. Z. Chowdhury and Y. Shibata, Chem. Pharm. Bull., 49(4), 391 (2001).
14. A. S. Galabov, B. S. Galabov, and N. A. Neykova, J. Med. Chem., 23, 1048 (1980).

1542
A. F. FAHMY ET AL.
15. S. Rollas, S. Buyuktimkin, and A. Cevikbas, Arch. Pharm. (Weinheim), 324, 189 (1991).
16. H. A. Abdel-Hamide, A. F. M. Fahmy, S. A. Shiba, and M. M. Hemdan, Egypt. J. Chem., 36(12),
149 (1993).
17. R. Bunnenberg and C. J. Jochims, Chem. Ber., 114, 1746 (1981).