Synthesis and antimicrobial activities of some heterocyclic systems from 2-furoyl isothiocyanate

Article abstract of DOI:10.1080/10426500902893209

2-Furoyl isothiocyanate (1) is used as a building block in synthesizing different heterocyclic systems of anticipated biological activities. Thus, isothiocyanate 1 was reacted with different nucleophilic reagents to produce five- and six-membered heterocyclic systems such as 1,2,4-triazoline, thiadiazolidine, quinazoline, benzothiazole, benzoxazole, benzimidazole, thiazolidine, and imidazolidine. The structures of all the synthesized compounds were confirmed by microanalytical and spectral data. The antimicrobial activity of some of the synthesized compounds was tested. 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.

Full text of DOI:10.1080/10426500902893209

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Synthesis and Antimicrobial Activities
of Some Heterocyclic Systems from 2-
Furoyl Isothiocyanate
Magdy M. Hemdan a
a Department of Chemistry, Faculty of Science, Ain Shams University,
Abbasia, Cairo, Egypt
Published online: 24 Feb 2010.
To cite this article: Magdy M. Hemdan (2010) Synthesis and Antimicrobial Activities of Some
Heterocyclic Systems from 2-Furoyl Isothiocyanate, Phosphorus, Sulfur, and Silicon and the Related
Elements, 185:3, 620-627, DOI: 10.1080/10426500902893209
To link to this article: http://dx.doi.org/10.1080/10426500902893209
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Phosphorus, Sulfur, and Silicon, 185:620–627, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500902893209
SYNTHESIS AND ANTIMICROBIAL ACTIVITIES OF SOME
HETEROCYCLIC SYSTEMS FROM 2-FUROYL
ISOTHIOCYANATE
Magdy M. Hemdan
Department of Chemistry, Faculty of Science, Ain Shams University, Abbasia,
Cairo, Egypt
2-Furoyl isothiocyanate (1) is used as a building block in synthesizing different heterocyclic
systems of anticipated biological activities. Thus, isothiocyanate 1 was reacted with different
nucleophilic reagents to produce five- and six-membered heterocyclic systems such as 1,2,4-
triazoline, thiadiazolidine, quinazoline, benzothiazole, benzoxazole, benzimidazole, thiazo-
lidine, and imidazolidine. The structures of all the synthesized compounds were confirmed
by microanalytical and spectral data. The antimicrobial activity of some of the synthesized
compounds was tested.
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 Benzothiazole; 2-furoyl isothiocyanate; quinazoline; thiadiazolidine; thiourea
derivatives; 1,2,4-triazoline
INTRODUCTION
1,2,4-Triazoles are known to exhibit anti-inflammatory,1 antiviral,2 analgesic,3 an-
timicrobial,4 anticonvulsant,5 and antidepressant activity.6 A series of 1,2,4-triazoles7 has
been patented and extensively employed in agriculture. In addition, it was reported that
1,3,4-thiadiazoles exhibit various biological activities due to the presence of the = N C S
moiety.8 Quinazolines exhibit a wide variety of pharmacological activities.9,10 The literature
also states that the antiviral11 and antibacterial12 activities of thiourea derivatives are due to
the presence of the NH C(S) NH function in the molecule, and the changes in this
activity depend on the nature of its substituents. In the present investigation, 2-furoyl isoth-
iocyanate is used as a building block to synthesize some new derivatives of 1,2,4-triazole,
thiadiazole, quinazoline, benzothiazole, benzoxazole, benzimidazole, thiazolidine, imida-
zole, and thiourea, and to investigate their antibacterial and antifungal activities.
Received 26 December 2008; accepted 13 March 2009.
Address correspondence to Magdy M. Hemdan, Department of Chemistry, Faculty of Science, Ain Shams
University 11566, Abbasia, Cairo, Egypt. E-mail: mhemdan39@hotmail.com
620

HETEROCYCLIC SYSTEMS FROM 2-FUROYL ISOTHIOCYANATE
621
RESULTS AND DISCUSSION
The reaction of 2-furoyl isothiocyanate (1) with benzoyl hydrazine (2a) in acetonitrile
produced the corresponding thiosemicarbazide derivative 3.13,14 Compound 3 so formed
could be readily converted into 1,2,4-triazoline-5-thione derivative 4 upon treatment with
polyphosphoric acid. The formation of 4 can be visualized on the basis of the removal
of a molecule of water. The structures of compounds 3 and 4 were elucidated from their
microanalytical and spectral data. Their IR spectra showed absorption bands corresponding
to NH in the region 3102–3300 cm−1, C O in the region 1640–1674 cm−1, and C S in the
region 1162–1173 cm−1. The 1H NMR spectra displayed signals due to aromatic protons
at 6.61–8.02 ppm integrating eight protons, and signals of NH protons in the downfield
region at 10.65–12.17 ppm. Their MS revealed molecular ion peaks at m/z 289 and m/z
271, respectively. Moreover, the appearance of 2-furoyl fragment at m/z 95 of compound 4
supported the proposed mechanism of its formation.
The reaction of hydrazine hydrate (2b) or phenyl hydrazine (2c) with isothiocyanate 1
in acetonitrile afforded 1,2,4-tiazoline derivatives 6a,b in a one-pot reaction. However, Uher
et al.15 have reported that the formation of 6 proceeded via isolation of thiourea derivatives
5a,b that underwent cyclization in an acid medium. On the other hand, when the reaction
of 1 with phenyl hydrazine (2c) was conducted in a dry acetone, thiadiazolidine derivative
7 was obtained; these results were consistent with our previous results14 and others.16 The
formation of compound 7 can be visualized on the basis of nucleophilic attack of isopropy-
lidene phenylhydrazone (obtained as a side product of the reaction of phenylhydrazine with
acetone) on the carbon atom of isothiocyanate group followed by cyclization (Scheme 1).
1
-H2O
PhNHNH2
CH3COCH3
Ph NHN = C(Me)2
+
Me
Me
Me
SH
Me
S
Me
Me
O
ArCON
S
O
N
N
Ar
N
H
N
N
NH
N
N
Ar
Ph
Ph
Ph
7
Scheme 1 Mechanism of formation of thiadiazoline derivative 7.
The IR spectra of triazolines 6a,b showed absorption bands correlated with NH and C S
groups. The IR spectrum of 7 showed absorption bands for NH and C O groups. The 1H
NMR spectrum of 6a displayed signals in the range 6.77–8.10 ppm corresponding to the
three furan protons and signals at δ 11.99 and 14.00 ppm for two NH protons. The 1H NMR
of 7 exhibited signals due to CH3 protons at δ 1.95 ppm, and those for aromatic protons in
the range 6.49–7.84 ppm and NH proton at 4.3 ppm. Heating of compound 7 with acetic
anhydride afforded its acetyl derivative 8 (Scheme 2).
Isothiocyanate 1 underwent reaction with thiosemicarbazide (2d) in boiling acetoni-
trile to yield 1,2,4-triazoline derivative 9.14,17 The mass spectrum of 9 showed its molecular
ion peak as well as a fragment corresponding to a furoyl cation at m/z 95 as a base peak.
Absorption bands correlated with NH, C O, and C S groups were recorded in its IR
spectrum. Further proof for the assigned structure of 9 was gained from microanalytical
and spectral studies of its mono acetyl derivative 10 (see the Experimental section).

622
M. M. HEMDAN
HN
N
O
O
poly-H3PO4
H
H
PhCONHNH2
Ar
S
N
Ph
N
N
N
N
H
Ph
AcOH
2a
O
S
Ar
N
3
4
R
RNHNH2
-H2O
H
H
R
Ar
N
N
NH
2b, R = H
2c, R = Ph
S
Ar
N
NCS
O
S
H
reflux
5a,b
O
6a,b
O
Ph
Ac
Ph
Ac2O
N
NH
PhNHNH2
1
N
N
CH3
CH3
CH3
CH3
2c / acetone
Ar-C-N
O
S
Ar-C-N
O
S
7
8
Ar =
Ac
S
O
HN
N
Ac2O
N
N
NH2CSNHNH2
O
O
Ar
N
N
Ar
N
H
S
N
2d
H
H
H
9
10
Scheme 2
The reaction of isothiocyanate 1 with anthranilic acid (11) yielded thiourea derivative
12, which cyclized upon heating with acetic anhydride to produce quinazoline derivative
13.14 The IR spectrum of compounds 12 and 13 showed absorption bands correlated with
ν NH, ν C O, and ν C S. The 1H NMR spectrum of 13 displayed signals due to aromatic
protons as well as a downfield signal due to the NH proton. Further support for the assigned
structures of 12 and 13 was gained from their MS data that showed their molecular ion
peaks (see the Experimental section).
A solution of isothiocyanate 1 in acetonitrile was refluxed with o-aminothiophenol
(14a), o-aminophenol (14b), or o-phenylenediamine (14c), which led to products for-
mulated as benzothiazole derivative 16a, benzoxazole derivative 16b, or benzimidazole
derivative 16c, respectively.14 The compounds 16a–c presumably formed via elimination
of H2S molecule from the non isolable thiourea derivatives 15a–c (Scheme 3). The IR
spectra of 16a–c showed absorption bands correlated with ν NH, ν C O. Their 1H NMR
spectra displayed signals in the region 6.61–8.05 ppm due to aromatic protons as well as
downfield signals for the NH protons. Further highlights for the proposed structures were
gained from their MS data that showed the molecular ion peaks (see the Experimental
section).
Refluxing of isothiocyanate 1 with thioglycolic acid (17a), 2-mercaptoethanol (17b),
or ethylglycinate (17c) in acetonitrile furnished adducts 18a–18c, respectively. Compounds
18a–18c could be readily converted into thiazolidine derivatives 19a,b or imidazolidine
derivative 19c upon heating with acetic anhydride and a catalytic amount of ammonium
acetate (Scheme 3). The structures of compounds 18a–c and 19a–c were elucidated from
their microanalytical and spectral data. The 1H NMR spectra of 18a–c displayed signals of
methylene protons and aromatic protons, as well as the signals of OH and NH protons in the
downfield region. 1H NMR spectra of 19a–c showed methylene proton signals as well as
the aromatic proton signals. The MS spectra of 18b,c and 19a–c revealed the corresponding
molecular ion peaks, which were in accord with their expected molecular formulas.
The antimicrobial screening of some of the synthesized compounds was done using
the agar plate diffusion method18 (see the Supplemental Materials available online).

HETEROCYCLIC SYSTEMS FROM 2-FUROYL ISOTHIOCYANATE
623
NH2
H
S
N
H
N
CO2
H
HN
Ar
Ac
2O
11
Ar
N
O
S
HO2C
O
O
12
13
XH
O
O
HX
SH
-H S
2
X
N
NCS
NH2
Ar
N
H
Ar
NH
O
N
14 a) X = SH
b) X =OH
O
16a) X = S,
b) X = O,
c) X = NH
c) X = NH
1
2
15a-c
S
Y
H
cyclisation
Ar
N
Y
x
XCH Y
2
Ar
N
X
17 a) X = CO H, Y = SH
O
S
2
b) X = CH OH, Y = SH
2
c) X = CO Et, Y = NH
2
2
18a-c
O
19a) X =CO, Y = S
b) X = CH , Y = S
2
c) X = CO, Y = NH
Scheme 3
EXPERIMENTAL
Melting points were determined in open capillary tubes on a Gallenkamp melt-
ing point apparatus and were uncorrected. The elemental analyses were done on a
Perkin–Elemer 2400 CHN elemental analyzer. The infrared spectra were recorded on FTIR
Maltson (infinity series) spectrometers as KBr discs. The 1H NMR spectra were measured
on Varian Gemini 200 MHz instrument with chemical shift (δ) expressed in ppm downfield
from TMS as internal standard, in DMSO-d6 or CDCl3. Mass spectra were recorded on a
Shimadzu GC-MSQP 1000 EX instrument operating at 70 eV. TLC carried out the moni-
toring of the progress of all reactions and homogeneity of the synthesized compounds. TLC
was run using TLC aluminum sheets silica gel F254 (Merck). The antimicrobial activity was
determined according to the method of Kavanagh.18 2-Furoylchloride was obtained from
Merck-Schuchardt, (d 20◦/4◦) 1.323–1.325.
Synthesis of 2-Furoyl Isothiocyanate (1)
The solution of 2-furoyl chloride (3 mmol) in dry acetonitrile or dry acetone (30 mL)
and solid ammonium thiocyanate (4 mmol) was stirred for 30 min at room temperature.19
The precipitated ammonium chloride was filtered off to give a clear solution of 2-furoyl
isothiocyanate (1) with 87% yield.
Reaction of 2-Furoyl Isothiocyanate (1) with 2a–d, 11, 14a–c, 17a–c
A solution of isothiocyanate 1 (3 mmol) in dry acetonitrile (30 mL) or dry acetone
(30 mL) was refluxed for 2–3 h (TLC) with an equimolar amount of benzoyl hydrazine
(2a), hydrazine hydrate (2b), phenyl hydrazine (2c), thiosemicarbazide (2d), anthranilic

624
M. M. HEMDAN
acid (11), o-aminothiophenol (14a), o-aminophenol (14b), o-phenylenediamine (14c), thio-
glycolic acid (17a), 2-mercaptothanol (17b), or ethylglycinate (17c). The precipitated solid
was filtered off and recrystallized from the suitable solvent.
1-Benzoyl-4-(2-furoyl)-thiosemicarbazide (3). 86% yield; colorless crystals;
mp 140–142◦C (ethanol); IR (KBr) ν: 3300, 3206, and 3120, 1668, 1640, 1162 cm−1; 1H
NMR (DMSO-d6) δ: 6.76 (d, J = 3.4 Hz, 1H), 7.54–7.63 (m, 3H), 7.87 (d, J = 3.6 Hz,
1H), 7.79 (d, J = 6.6 Hz, 2H), 8.02 (s, 1H), 11.10 (br.s, 1H), 11.54 (br.s, 1H), 12.17 (br.s,
1H); MS (70 eV) m/z (%): 289 (M+., 30), 290 (M+.+1, 13), 291 (M+.+2, 4), 272 (22), 256
(26), 105 (100), 95 (70), 77 (29); Anal. Calcd. for C13H11N3O3S (289.31); C, 53.97; H,
3.83; N, 14.52. Found: C, 53.88; H, 3.76; N, 14.43%.
3-(2-Furoyl)-1,2,4-triazoline-5-thione (6a). 84% yield; colorless crystals; mp
>300◦C (acetic acid); IR (KBr) ν: 3283, 3118, 1670, 1170 cm−1; 1H NMR (DMSO-d6) δ
6.77 (d, J = 1.8 Hz, 1H), 7.90 (d, J = 3.6 Hz, 1H), 8.10 (s, 1H), 11.99 (br.s, 1H), 14.00
(br.s, 1H); Anal. Calcd for C6H5N3OS (167.19); C, 43.10; H, 3.01; N, 25.13. Found; C,
42.93; H, 2.86; N, 24.79%.
2-Phenyl-3-(2-furayl)-1,2,4-triazoline-5-thione (6b). 84% yield; colorless
crystals; mp 232–233◦C (toluene); IR (KBr) ν: 3106, 1635, 1171 cm−1 1H NMR
;
(DMSO-d6) δ: 6.65 (d, J = 1.8 Hz, 1H), 7.54 (d, J = 2.6 Hz, 3H,), 7.82 (d, J = 3.6 Hz,
1H), 7.91 (dd, J = 2.0, J = 3.3 Hz, 2H), 8.04 (s, 1H), 9.87 (br.s, 1H); MS m/z (%) 243
(M+., 55), 245 (M+.+2, 4), 244 (M+.+1, 11), 242 (100), 91 (72), 90 (77). Anal. Calcd for
C12H9N3OS (243.28); C, 59.24; H, 3.73; N, 17.27. Found; C, 59.19; H, 3.64; N, 17.19%.
2-(2-Furoylimino)-3-phenyl-5,5-dimethyl-1,3,4-thiadiazolidine (7). 78%
yield; mp 176–177◦C ethyl alcohol; IR (KBr) ν: 3186, 2974, 1614, 1560 cm−1; 1H NMR
(CDCl3) δ 1.95 (s, 6H), 4.3 (br.s, 1H), 6.49 (dd, J = 1.8, 2.7 Hz, 1H), 7.20 (d, J = 3.6 Hz,
1H), 7.24–7.32 (m, 1H), 7.47 (t, J = 7.4, 8.3, Hz, 2H), 7.59 (s, 1H), 7.84 (d, J = 7.8 2H);
Anal. Calcd for C15H15N3O2S (301.36) C, 59.78; H, 5.02; N, 13.94. Found: C, 59.31; H,
4.83; N, 13.44; S, 10.32%.
3-(2-Furoylamido)-3H-4H-1,2,4-triazolin-5-thione (9). 89% yield; colorless
crystals; mp 298–300◦C (acetic acid); IR (KBr) ν: 3392, 3270, 3130 (NH), 1695, 1613,
1282 cm−1; 1H NMR (DMSO-d6) δ 2.9 (br. s, 1H), 6.45–6.85 (m, 1H), 7.77–7.83 (m, 1H),
8.10 (s, 1H), 9.7 (br.s, 1H); 12.7, (br.s, 1H); MS (70 eV) m/z (%): 210 (M+., 5), 182 (11),
116 (8), 95 (100); Anal. Calcd for C7H6N4O2S (210.21); C, 40.00; H, 2.88; N, 26.65.
Found: C, 39.83; H, 2.75; N, 26.59%.
2-(3-Furan-2-carbonylthioureido)benzoic acid (12). 82% yield; colorless
crystals; mp 173◦C with decomposition, (ethanol); IR (KBr) ν: 3290, br.3170–2400,
1
1690, 1650, 1150 cm−1; H NMR (DMSO-d6) δ 6.73 (s, 1H), 7.55–7.84 (m, 4H), 7.92
(d, J = 3.6 Hz, 1H), 8.09 (s, 1H), 11.99 (br.s, 1H), 12.79 (br.s, 1H), 13.52 (br.s, 1H);
MS (70 eV) m/z (%): 290 (M+., 10), 291 (, M+.+1, 2), 262 (4), 245 (6), 95 (100); Anal.
Calcd for C13H10N2O4S (290.29); C, 53.79; H, 3.47; N, 9.65. Found: C, 53.47; H, 3.25;
N, 9.51%.
N-(Benzo[d]thiazol-2-yl)furan-2-carboxamide (16a). 65% yield; colorless
crystals, mp 188–190◦C (petroleum ether bp 60–80◦C); IR (KBr) ν: 3314, 1656, 1600
cm−1; 1H NMR (CDCl3) δ: 6.63 (s, 1H), 7.37–7.56 (m, 4H), 7.68 (d, J = 8.1 Hz, 1H), 7.87
(d, J = 7.8 Hz, 1H), 11.77 (br.s, 1H); MS (70 eV) m/z (%): 244 (M+., 23), 245 (M+.+1, 6),
246 (M+.+2, 2), 216 (47), 95 (100); Anal. Calcd for C12H8N2O2S (244.27); C, 59.00; H,
3.30; N, 11.47. Found: C, 58.96; H, 3.15; N, 11.39%.
N-(Benzo[d]oxazol-2-yl)furan-2-carboxamide (16b). 62% yield; colorless
crystals, mp 135–137◦C (petroleum ether b.p 60–80◦C); IR (KBr) ν: 3350, 1677, 1620

HETEROCYCLIC SYSTEMS FROM 2-FUROYL ISOTHIOCYANATE
625
1
cm−1; H NMR (DMSO-d6) δ 6.61 (s, 2H), 7.11 (d, J = 3.2 Hz, 2H), 7.37 (br.s, 1H),
7.77–7.81 (m, 3H); MS (70 eV) m/z (%): 228 (M+., 61), 229 (M+.+1, 10), 227 (M+.-1, 4),
118 (7), 110 (9), 109 (15), 95 (100); Anal. Calcd. C12H8N2O3 (228.20) C, 63.16; H, 3.53;
N, 12.28. Found: C, 62.68; H, 3.22; N, 11.95%.
N-(1H-Benzo[d]imidazol-2-yl)furan-2-carboxamide (16c). 68% yield; col-
1
orless crystals, mp 144–146◦C (ethanol); IR (KBr) ν: 3300, 3195, 1671, 1622 cm−1; H
NMR (DMSO-d6) δ: 6.61 (d, J = 6.4 Hz, 1H), 6.71–6.79 (m, 2H), 6.97–7.05 (m, 1H), 7.28
(d, J = 6.8 Hz, 1H), 7.83 (d, J = 3.0 Hz, 1H), 8.05 (d, J = 1.0 Hz, 1H), 11.14 (br.s, 1H),
11.70, (br.s, 1H); MS (70 eV) m/z (%): 227 (M+., 51), 228 (M+.+1, 8), 117 (11), 95 (100);
Anal. Calcd for C12H9N3O2 (227.22); C, 63.43; H, 3.99; N, 18.49. Found: C, 63.18; H,
3.78; N, 18.33%.
Carboxymethyl N-(2-Furoyl)dithiocarbamate (18a). 79% yield; yellow crys-
tals, mp 171◦C with decomposition, (ethanol); IR (KBr) ν: 3350, (br.) 3200–2400, 1710,
1670, 1090 cm−1; 1H NMR (CDCl3) δ: 4.10 (s, 2H), 5.28 (br.s 1H), 6.75–6.77 (m, 1H), 7.84
(d, J = 3.6 Hz, 1H), 8.01 (s, 1H), 12.68 (br.s 1H); Anal. Calcd for C8H7NO4S2 (245.28);
C, 39.17; H, 2.88; N, 5.71. Found: C, 38.89; H, 2.71; N, 5.55%.
2-Hydroxyethyl N-(2-Furoyl)dithiocarbamate (18b). 77% yield; yellow crys-
tals; mp 130–132◦C (petroleum ether bp 60–80◦C); IR (KBr) ν: 3492, 3134, 1673, 1205
cm−1; 1H NMR (DMSO-d6) δ: 3.34–3.39 (m, 2H), 3.69–3.74 (m, 2H), 5.04 (br. s, 1H), 6.75
(s, 1H), 7.81 (s, 1H), 8.07 (s, 1H), 12.45 (br.s, 1H); MS (70 eV) m/z (%): 231 (M+., 1), 214
(5), 213 (17) 187 (8), 154 (100), 95 (14); Anal. Calcd for C8H9NO3S2 (231.29); C, 41.54;
H, 3.92; N, 6.05. Found: C, 41.36; H, 3.78; N, 5.87%.
Ethyl-2-(3-furan-2-carbonylthioureido)acetate (18c). 91% yield; colorless
1
crystals, mp 100–102 (ethanol); IR (KBr) ν: 3292, 3206, 1750, 1676, 1286 cm−1; H
NMR (CDCl3) δ: 1.34 (t, J = 7.1 Hz, 3H), 4.30 (q, J = 7.2 Hz, 2H), 4.7 (d, J = 4.8 Hz,
2H), 6.62–6.65 (m, 1H), 7.38 (d, J = 3.6 Hz, 1H,), 7.61 (s, 1H), 9.24 (br.s, 1H), 11.43
(br.s, 1H); MS (70 eV) m/z (%): 256 (M+., 17), 257 (M+.+1, 4), 228 (15), 227 (2), 210 (5),
95 (100); Anal. Calcd for C10H12N2O4S (256.28); C, 46.87; H, 4.72; N, 10.93. Found: C,
46.75; H, 4.68; N, 10.70%.
Formation of Compounds 8, 10, 13, 19a,b
The solution of corresponding compounds 7, 9, 12, and 18a,b (0.01 mol) in acetic
anhydride was refluxed for 1–2 h (TLC) on a water bath, then left to cool at room temper-
ature. The precipitated solid obtained after addition of ice cold water was filtered off and
recrystallized from a suitable solvent.
2-(2-Furoylimino)-3-phenyl-4-acetyl-5,5-dimethyl-1,3,4-thiadiazolidine
(8). 79% yield; mp 122–123◦C (ethyl alcohol); IR (KBr) ν: 1694, 1666, 1630, cm−1; 1H
NMR (CDCl3) δ: 1.89 (s, 3H) 1.96 (s, 6H), 6.56 (dd, J = 1.8, 1.9 Hz, 1 H), 7.23 (d, J =
3.7 Hz, 1H,), 7.28–7.35 (m, 1H), 7.51 (t, J = 7.7 Hz, 2H), 7.61 (s, 1H), 7.91 (d, J = 7.3
Hz, 2H,); Anal. Calcd for C17H17N3O3S (343.30) C, 59.46; H, 4.99; N, 12.24. Found: C,
59.39; H, 4.95; N, 12.18%.
1-Acetyl-3-(2-fourylamido)-3H-4H-1,2,4-triazolin-5-thione
(10). 89%
yield; colorless crystals; mp 347–350◦C (DMF); IR (KBr) ν: 3225, 3132, 1709, 1690,
1
1650, 1582 cm−1; H NMR (DMSO-d6) δ 2.2 (s, 3H), 6.71–6.75 (m, 1H), 7.61–7.67 (m,
1H), 8.01 (s, 1H), 12.2 (br.s, 1H), 12.7, (br.s, 1H); MS (70 eV) m/z (%): 252 (M+., 11),

626
M. M. HEMDAN
210 (28), 224 (25), 158 (4), 95 (100); Anal. Calcd for C9H8N4O3S (252.25); C, 42.85; H,
3.20; N, 22.21. Found: C, 42.77; H, 3.16; N, 22.19%.
3-(Furan-2-carbonyl)-2-thioxo-2,3-dihydroquinazolin-4(1H)-one
(13).
77% yield; colorless crystals, mp 189–190◦C (ethanol); IR (KBr) ν: 3220, 1690, 1635,
1190 cm−1; 1H NMR (DMSO-d6) δ 6.75–6.79 (m, 1H), 7.54 (t, J = 7.0 Hz, 1H), 7.69–7.77
(m, 2H), 7.90 (t, J = 6.8 Hz, 1H), 8.04 (d, J = 5.0 Hz, 1H), 8.10 (d, J = 5.4 Hz, 1H),
12.34 (br.s, 1H); MS (70 eV) m/z (%): 272 (M+., 24), 274 (M+.+2, 3), 273 (M+.+1, 10),
244 (100), 162 (18), 95 (80); Anal. Calcd for C13H8N2O3S (272.28) C, 57.35; H, 2.96; N,
10.29. Found: C, 57.10; H, 2.78; N, 10.05%.
3-(Furan-2-carbonyl)-2-thioxo thiazolidin-4-one (19a). 60% yield; yellow
crystals; mp 115–117◦C (petroleum ether bp 60–80◦C); IR (KBr) ν: 1780, 1720, 1205
1
cm−1; H NMR (CDCl3) δ: 4.22 (s, 2H), 6.65 (s, 1H), 7.82–7.84 (m, 1H), 8.08 (s, 1H);
MS (70 eV) m/z (%): 227 (M+., 14), 228 (M+.+1, 2), 199 (40), 95 (100); Anal. Calcd for
C8H5NO3S2 (227.26) C, 42.28; H, 2.22; N, 6.16. Found: C, 41.95; H, 2.05; N, 5.93%.
3-(Furan-2-carbonyl)-2-thioxo thiazolidine (19b). 50% yield; yellow crystals;
mp 76–78◦C (petroleum ether bp 60–80◦C); IR (KBr) ν: 2928, 1638, 1286 cm−1; 1H NMR
(DMSO-d6) δ: 3.78–4.39 (m, 4H), 6.73 (s, 1H), 7.83 (s, 1H), 8.05 (s, 1H); MS (70 eV)
m/z (%):213(M+., 39), 215 (M+.+2, 4), 214 (M+.+1, 9), 185 (5), 95 (100); Anal. Calcd for
C8H7NO2S2 (213.28) C, 45.05; H, 3.31; N, 6.57. Found: C, 44.83; H, 3.19; N, 6.44%.
3-Phenyl-4-(2-furoyl)-1H-1,2,4-triazoline-5-thione (4)
A solution of compound 3 (0.01 mol) 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 acetic acid; 75% yield; colorless crystals; mp
1
261–263◦C; IR (KBr) ν: 3134, 3102, 1674, 1537, 1173 cm−1; H NMR (CDCl3) δ: 6.61
(d, J = 1.8 Hz, 1H,), 7.51 (d, J = 2.4 Hz, 3H,), 7.62 (d, J = 3.6 Hz, 1H), 7.69 (s, 1H), 7.96
(dd, J = 2.1, J = 3.3 Hz, 2H), 10.65 (br.s, 1H); MS (70 eV) m/z (%): 271 (M+., 7), 272
(M+.+1, 1), 242 (26),175 (3), 95 (89), 94 (100), 77 (15); Anal. Calcd. for C13H9N3O2S
(271.29) C, 57.55; H, 3.34; N, 15.49. Found: C, 57.48; H, 3.26; N, 15.44%.
3-(Furan-2-carbonyl)-2-thioxoimidazolidin-4-one (19c)
A solution of 18c (0.01 mol) in glacial acetic acid (30 mL) and ammonium acetate
(0.5 g) was refluxed for 2h, then left to cool at room temperature. The precipitated solid
obtained after addition of ice cold water was filtered off and recrystallized from petroleum
ether, bp 60–80◦C; 76% yield; colorless crystals, mp 82–84◦C IR (KBr) ν: 3182, 1666,
1272 cm−1; 1H NMR (CDCl3) δ: 4.3 (s, 2H), 6.63 (s, 1H), 7.32 (d, J = 3.4 Hz, 1H,), 8.01
(s, 1H), 10.43 (br.s, 1H); MS (70 eV) m/z (%): 210 (M+., 11), 211(M+. +1, 2), 182 (15), 95
(100); Anal. Calcd for C8H6N2O3S (210.01) C, 45.71; H, 2.88; N, 13.33. Found: C, 45.35;
H, 2.64; N, 13.09%.
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