Reaction with hydrazonoyl halides 64: Synthesis of some new triazolino[4,3-a]pyrimidines, 1,3,4-thiadiazoles, and 5-arylazothiazoles

Article abstract of DOI:10.1002/jhet.945

2,3-Dihydro-1,3,4-thiadiazoles, 2,3-dihydro-1,3,4-selenadiazoles, and triazolino[4,3-a]pyrimidines containing benzofuran moiety were prepared from the reaction of 2-(2-phenylhydrazono)-1-(5-bromobenzofuran-2-yl)-2-chloroethanone with each of potassium thi

Full text of DOI:10.1002/jhet.945

1098
Reaction with Hydrazonoyl Halides 64: Synthesis of Some New
Triazolino[4,3-a]pyrimidines, 1,3,4-Thiadiazoles, and
5-Arylazothiazoles
Vol 49
*
Abdou O. Abdelhamid, Abdelgawad A. Fahmi, and Basma S. Baaui
Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt
*
E-mail: Abdelhamid45@gmail.com
Received December 1, 2010
DOI 10.1002/jhet.945
Published online 26 October 2012 in Wiley Online Library (wileyonlinelibrary.com).
2,3-Dihydro-1,3,4-thiadiazoles, 2,3-dihydro-1,3,4-selenadiazoles, and triazolino[4,3-a]pyrimidines con-
taining benzofuran moiety were prepared from the reaction of 2-(2-phenylhydrazono)-1-(5-bromobenzo-
furan-2-yl)-2-chloroethanone with each of potassium thiocyanate, potassium selenocyanate, alkyl
carbodithioate, and pyrmidine-2-thione derivatives. All the newly synthesized compounds were con-
firmed by elemental analysis, spectral data, and alternative route synthesis whenever possible.
J. Heterocyclic Chem., 49, 1098 (2012).
INTRODUCTION
dihydro-3-(5-bromobenzofuran-2-oyl)-7-dimethyl-1,5-
diphenyl-[1,2,4]triazolo[4,3-a]pyrimidine-6-carboxylate
(9a; Scheme 1). The structure of 9a was elucidated on
the basis of both elemental analysis and spectral data
1,3,4-Thiadiazoles have been screened for their antibacte-
rial and antifungal activities [1–4], anti-inflammatory [5],
antituberculosis activity [6], and anticancer [7]. Also, the
benzofuran ring system occurs widely in natural products as
well as in synthetic substances, which have been reported to
exhibit a variety of important pharmacological properties
[8]. Moreover, a series of benzofuran derivatives have been
reported to inhibit the fibril formation in the b-amyloid pep-
tide [9], which is believed to be the underlying cause of Alz-
heimer’s disease [10, 11]. Here, we report the convenient
synthesis of triazolino[4,3-a]pyrimidines, 2,3-dihydro-1,3,4-
thiadiazoles, 2,3-dihydro-1,3,4-selenadiazoles, and 5-aryla-
zothiazole derivatives containing benzofuran moiety.
1
as well as alternative synthesis. H NMR spectrum of
9a showed signals at d = 1.16 (t, 3H, CH3CH2), 2.24
(s, 3H, CH3), 4.21 (q, 2H, CH2CH3), 6.15 (s, 1H, CH),
and 7.12–8.11 (m, 14H, ArH). Its IR spectrum revealed
bands at n = 1735 cmꢀ1 (CO).
Ethyl 6-methyl-4-[4-phenyl-2-methylthio-3,4-dihydropyri-
midine-5-carboxylate (10a) [13] reacted with 4 in boiling
ethanolic sodium ethoxide solution gave products identical
in all aspects (mp, mixed mp, and spectral data) with the cor-
responding 9a. Analogously, treatment of the appropriate 4
with the appropriate 5b–h gave tiazolo[4,3-a]pyrimidines
9b–h, respectively (Scheme 1). The formation of 9b–h can
be explained via 1,3-dipolar cycloaddition or 1,3-addition of
nitrile imides 6 (prepared in situ from hydrazonoyl bromide
4 with triethylamine or sodium ethoxide) to C═S of 5 (or
NH of 10) to give intermediates 7–8 (or 11), with ring open-
ing and ring closure to afford the final products 9 by elimina-
tion of hydrogen sulfide (or methyl mercaptan; Scheme 1).
RESULTS AND DISCUSSION
Treatment of 2-(2-phenylhydrazono)-1-(5-bromoben-
zofuran-2-yl)-2-chloroethanone (4) with ethyl 4-methyl-
6-phenyl-2-thioxo-1,3,6-trihydropyrimidine-5-carboxylate
(5a) [12] in chloroform and triethylamine gave ethyl 1,5-
© 2012 HeteroCorporation

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Reaction with Hydrazonoyl Halides 64: Synthesis of Some New
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Triazolino[4,3-a]pyrimidines, 1,3,4-Thiadiazoles, and 5-Arylazothiazoles
Scheme 1
Similarly, reactions of 2-thioxo-2,3-dihydro-1H-
quinazolin-4-one [14], 2-mercaptobenzimidazole, and
2-thioxo-2,3,5,6,7,8-hexahydro-1H-benzo[4,5]thieno[2,3-d]
pyrimidin-4-one [15] with hydrazonoyl bromide 4 were
carried out in refluxing chloroform by triethylamine gave
[1,2,4]triazolo[3,4-b]quinazolin-5-one 12, 1H-benzo
[4,5]imidazo[2,1-c][1,2,4]triazol-3-yl)-methanone 13,
and 1,2,3a,10-tetraaza-cyclopenta[b]fluoren-4-one 14,
respectively (Scheme 2).
These results indicate that hydrazone 16 is not the
final products and readily gave 17 by cyclization (Scheme
3). Nitrosation of each 17a and 17c with saturated sodium ni-
trite in acetic acid at 0–5ꢁC gave (5-bromobenzofuran-2-yl)
(4,5-dihydro-5-nitrosoimino-4-phenyl-1,3,4-thiadiazol-2-
yl)methanone (18a) and (5-bromobenzofuran-2-yl)(4,5-
dihydro-5-nitrosoimino-4-phenyl-1,3,4-selenadiazol-2-yl)
methanone (18c), respectively. 5-(5-Bromo-benzofuran-
2-carbonyl)-3-phenyl-3H-[1,3,4]thiadiazol-2-one (19a)
Also, treatment 4 with potassium thiocyanate and po-
tassium selenocyanate gave (5-bromobenzofuran-2-yl)(4,5-
dihydro-5-imino-4-phenyl-1,3,4-thiadiazol-2-yl)methanone
(17a) and (5-bromobenzofuran-2-yl)(4,5-dihydro-5-imino-
4-phenyl-1,3,4-selenadiazol-2-yl)methanone (17c), respec-
tively (Scheme 3). The structures of 17a and 17c were
elucidated on the basis of elemental analyses, spectral data,
alternative synthetic route, and its chemical transformation.
and
5-(5-bromo-benzofuran-2-carbonyl)-3-phenyl-3H-
[1,3,4]selenadiazol-2-one (19c) were prepared by thermo-
lysis of 18a and 18c in boiling xylene. IR spectra of 19a
and 19c revealed bands at n = 1685 cmꢀ1 (CO). Acety-
lation of 17a with acetic anhydride and benzoylation
with benzoyl chloride in pyridine afforded N-[5-(5-
bromo-benzofuran-2-carbonyl)-3-phenyl-3H-[1,3,4]thiadiazol-2-
ylidene]-acetamide (20a) and N-[5-(5-bromo-benzofuran-
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A. O. Abdelhamid, A. A. Fahmi, and B. S. Baaui
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Scheme 2
More evidence on the correct structure of 17 came
from reaction of arenediazonium chloride with 15 in
ethanolic sodium acetate solution gave a products identi-
cal in all aspects (mp, mixed mp, and spectra) with 17.
Analogously, diazotization of each anthranilic acid and
methyl anthranilate reacted with the appropriate 15a,b
gave one isolable product, in each case, as: 2-(5-bromo-
benzofuran-2-carbonyl)-3-thia-1,4,9b-triaza-cyclopenta
[a]naphthalen-5-one (22a) and 2-(5-bromo-benzofuran-2-
carbonyl)-3-selena-1,4,9b-triaza-cyclopenta[a]naphthalen-
5-one (22b), respectively, in a good yield (Scheme 3).
In contrast, treatment of 4 with thiourea in boiling eth-
anol gave 5-(2-phenyldiazenyl)-2-(5-bromobenzofuran-2-
yl)thiazol-4-amine (25a; spectral data, elemental analysis,
and alternative synthetic route confirmed the structure).
1H NMR spectrum of 20a showed signals at d = 7.23–
7.69 (m, 8H, ArH0s) and 8.25 (s, br., 2H, NH2). Thus,
treatment of benzenediazonium chloride with 2-(5-
bromo-benzofuran-2-yl)-thiazol-4-ylamine (26), which
prepared from reaction of thiourea with 2 in ethanol,
gave product identical in all aspects (mp, mixed mp, and
spectra) with 25.
2-carbonyl)-3-phenyl-3H-[1,3,4]thiadiazol-2-ylidene]-
benzamide (21a), respectively. 1H NMR spectrum of
20a showed signals at d = 2.10 (s, 3H, CH3CO), 2.40
(s, 3H, CH3CON), 7.40 (d, 2H, J = 8 Hz, ArH0s),
7.50 (d, 2H, J = 8Hz, ArH0s), 8.00 (d, 4H, J = 8Hz,
ArH0s).
Scheme 3
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Triazolino[4,3-a]pyrimidines, 1,3,4-Thiadiazoles, and 5-Arylazothiazoles
Compound 4 reacted with alkyl carbodithioates 27a [16,
17] to give [5-(benzylidene-hydrazono)-4-phenyl-4,5-
dihydro-[1,3,4]thiadiazol-2-yl]-(5-bromo-benzofuran-2-yl)-
methanone (31a; Scheme 4). The structure of 30a was
confirmed by elemental analysis, spectral data, and alterna-
6-trihydropyrimidine-5-carboxylate, potassium thiocyanate,
potassium selenocyanate, alkyl carbodithioate.
EXPERIMENTAL
1
tive synthetic route. H NMR spectrum of 31a showed
All melting points were determined on an Electrothermal melt-
ing point apparatus and are uncorrected. IR spectra were recorded
(KBr discs) on a Shimadzu FT-IR 8201 PC spectrophotometer.
The 1H NMR and 13C NMR spectra were taken on a Varian
Gemini 300 MHz spectrometer in CDl3 or DMSO-d6 using
TMS as internal standard, and chemical shifts are expressed in d
(ppm) values. Mass spectra were taken on a Shimadzu GCMS-
GB PX and Shimadzu GCMS-QP1000 EX mass spectrometer
and operating at 70 eV. Elemental analyses were carried out at
Microanalytical Center of the University of Cairo, Giza, Egypt.
2-Mercaptobenzimidazole was supplied by MERCK (Germany).
2-Bromo-1-(5-bromobenzofuran-2-yl)ethanone (2). Bromine
[16 g (5 mL), 0.1 mmol] was added portion wise to 2-acetyl-5-
bromobenzofuran (23.8 g, 0.1 mmol) in dioxan–ether (50 mL)
while stirring for 15 min. The reaction mixture was then poured
on ice cold water (200 mL). The resultant solid residue was
collected and recrystallized from ethanol to give pale yellow
crystals, yield (75%), mp 132–33ꢁC; IR (KBr): 3098 (CH,
signals at d = 2.10 (s, 3H, CH3), and 7.54–8.53 (m, 11H,
ArH0s), 8.40 (d, 2H, ArH0s), and 8.52 CH (vinyl). Thus,
treatment of 4 with 28a in ethanolic triethylamine gave a
product identical in all aspects (mp, mixed mp, and spectra)
with 30a. Analogously, treatment of 4 with the appropriate
27b–n in ethanolic triethylamine afforded 1,3,4-thiadiazoline
derivatives 31b–n, respectively (Scheme 4).
Finally, (5-bromo-benzofuran-2-yl)-(4-phenyl-5-phe-
nylimino-4,5-dihydro-[1,3,4]thiadiazol-2-yl)-methanone
(32) was obtained from reaction of 4 with methyl
phenyldithiocarbamate.
CONCLUSIONS
Some new triazolino[4,3-a]pyrimidine, 1,3,4-thiadia-
zole, 1,3,4-selenadiazole, and 5-arylazothiazole deriva-
tives containing benzofuran moiety were obtained in a
good yield via reaction of 2-(2-phenylhydrazono)-1-(5-
bromobenzofuran-2-yl)-2-chloroethanone with the ap-
propriate of ethyl 4-methyl-6-substituted 2-thioxo-1,3,
1
aromatic), 1690 (CO), 1594 (C═C); H NMR: d = 4.43 (s, 2H,
CH2); 7.65–7.94 (m, 4H, ArH0s); 13C NMR d = 25.68, 107.85,
113.25, 116.45, 124.21, 127.65, 129.11, 142.77, 153.21, 185.87;
Anal. Calcd. For C10H6Br2O2 requires (317.96): C, 37.77; H,
1.90; Br, 50.26. Found: C, 37.65; H, 2.10; Br, 50.34%.
Scheme 4
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A. O. Abdelhamid, A. A. Fahmi, and B. S. Baaui
Vol 49
1-(5-Bromobenzofuran-2-yl)ethanone-2-oxodimethylsulfonium
CH3), 4.11 (q, 2H, J = 7.5 Hz, CH2CH3), 6.15 (s, 1H, pyrimidine H-
4), 7.14–8.14 (m, 13H, ArH0s); 13C NMR d = 13.25, 17.51, 19.89,
55.12, 58.62, 101.42, 113.21, 115.41, 118.38, 123.95, 123.99,
126.58, 127.62, 129.42, 130.11, 133.12, 137.92, 142.54, 149.24,
151.28, 153.19, 160.78, 164.78, 173.58; Anal. Calcd. For
C31H25BrN4O4 requires (597.46): C, 62.32; H, 4.22; Br, 13.37; N,
9.38. Found: C, 62.23; H, 4.34; Br, 13.42; N, 9.51%.
Ethyl 3-(5-bromo-benzofuran-2-carbonyl)-5-(4-methoxyphenyl)-
7-methyl-1-phenyl-1,5-dihydro-[1,2,4]triazolo[4,3-a]pyrimidine-6-
carboxylate (9c). This compound was obtained as red crystals
(acetic acid), yield (72%), mp 157–60ꢁC; IR (KBr): 3098 (CH,
aromatic), 1715 (CO, ester), 1658 (CO), 1612 (C═N), 1594
(C═C); 1H NMR: d = 1.23 (t, 3H, J = 7.5 Hz, CH2CH3), 2.58 (s,
3H, CH3), 3.69 (s, 3H, OCH3), 4.12 (q, 2H, J = 7.5 Hz,
CH2CH3), (s, 1H, pyrimidine H-4), 7.14–8.14 (m, 13H, ArH0s);
13C NMR d = 13.25, 17.51, 55.12, 55.30, 58.62, 101.42, 113.21,
115.41, 118.38, 123.95, 123.99, 126.58, 127.62, 129.42, 130.11,
133.12, 137.92, 142.54, 149.24, 151.28, 153.19, 160.78, 164.78,
173.58; Anal. Calcd. For C31H25BrN4O5 requires (616.05): C,
60.69; H, 4.11; Br, 13.03; N, 9.13. Found: C, 60.85; H, 4.23; Br,
13.30; N, 9.32%.
bromide (3). A mixture of 2 (30.3 g, 0.1 mol) and dimethylsulfide
(6.8 g, 0.11 mol) in ethanol (75 mL) was boiled under reflux
for 30 min. The reaction mixture was then cooled, and the
solid collected by filtration and recrystallized from ethanol to
give yellow crystals, yield (70%), mp 162–64ꢁC; IR (KBr):
3081 (CH, aromatic), 1665 (CO), 1592 (C═C); 1H NMR:
3.18 (s, 6H, 2CH3), 4.11 (s, 2H, CH2), 7.52–7.85 (m, 4H,
ArH0s); Anal. Calcd. For C12H12Br2O2S requires (380.1): C,
37.92; H, 3.18; Br, 42.04; S, 8.44. Found: C, 38.12; H,
3.31; Br, 41.88; S, 8.56%.
2-(2-Phenylhydrazono)-2-bromo-1-(5-bromobenzofuran-2-
yl)ethanone (4). A mixture of 3 (36.5 g, 0.1 mol) and the
appropriate N-nitrosoacetanilide (16 g, 0.11 mol) was stirred in
ethanol (100 mL) for 3 h at room temperature. The resulting solid
was collected and recrystallized from acetic acid to give yellow
crystals. Yield (75%), mp 198–200ꢁC; IR (KBr): 3075 (CH,
1
aromatic), 1662 (CO), 1596 (C═C); H NMR: d = 6.82 (t, 1H,
J = 8Hz, ArH), 7.22 (t, 2H, J = 8 Hz, ArH0s), 7.25 (d, 2H, J = 8Hz,
ArH0s), 7.82–7.92 (m, 4H, ArH0s), 11.80 (s, br., 1H, NH); 13C NMR
d = 113.21, 114.34, 115.21, 116.01, 122.11, 124.45, 125.78, 127.31,
129.11, 131.32, 146.71, 147.62, 156.25, 174.13; Anal. Calcd. For
C16H10Br2N2O2 requires (422.07): C, 45.53; H, 2.39; Br, 37.86; N,
6.64. Found: C, 45.37; H, 2.42; Br, 37.68; N, 6.55%.
Ethyl 3-(5-bromo-benzofuran-2-carbonyl)-5-(4-chlorophenyl)-
7-methyl-1-phenyl-1,5-dihydro-[1,2,4]triazolo[4,3-a]pyrimidine-
6-carboxylate (9d). This compound was obtained as red crystals
(acetic acid), yield (78%), mp 190–93ꢁC; IR (KBr): 3098 (CH,
aromatic), 1712 (CO, ester), 1660 (CO), 1617 (C═N), 1594
Synthesis of ethyl 3-(5-bromo-benzofuran-2-carbonyl)-7-
methyl-1-phenyl-5-substituted 1,5-dihydro-[1,2,4]triazolo[4,3-
a]pyrimidine-6-carboxylate 9a–h and 12–14. Method A. A
suspension of the appropriate ethyl 4-methyl-6-substituted 2-
thioxo-1,3,6-trihydropyrimidine-5-carboxylate 5a–h (5 mmol) in
chloroform (25 mL) was refluxed with 2-(2-phenylhydrazono)-2-
bromo-1-(5-bromobenzofuran-2-yl)ethanone (4; 1.97 g, 5 mmol)
and triethylamine (0.7 mL, 5 mmol) for 20 h. The excess solvent
was evaporated, and the residue was triturated with methanol (10
mL). The solid formed was collected and crystallized from acetic
acid to give analytically pure product.
1
(C═C); H NMR: d = 1.23 (t, 3H, J = 7.5 Hz, CH2CH3), 2.56 (s,
3H, CH3), 4.12 (q, 2H, J = 7.5 Hz, CH2CH3), (s, 1H, pyrimidine
H-4), 7.14–8.14 (m, 14H, ArH0s); 13C NMR d = 13.25, 17.51,
55.30, 58.62, 101.42, 113.21, 115.41, 118.38, 123.95, 123.99,
126.58, 127.62, 129.42, 130.11, 133.12, 137.92, 142.54, 149.24,
151.28, 153.19, 160.78, 164.78, 173.58; Anal. Calcd. For
C30H22BrClN4O4 requires (617.88): C, 58.32; H, 3.59; Br, 12.93;
Cl, 5.74; N, 9.07. Found: C, 58.23; H, 3.65; Br, 13.13; Cl, 5.81; N,
8.88%.
3-(5-Bromo-benzofuran-2-carbonyl)-5-(2,3-dimethoxy-phenyl)-
7-methyl-1-phenyl-1,5-dihydro-[1,2,4]triazolo[4,3-a]pyrimidine-6-
carboxylate (9e). This compound was obtained as yellow crystals
(acetic acid), yield (68%), mp 146–48ꢁC; IR (KBr): 3071 (CH,
aromatic), 2960 (CH, aliphatic), 1700 (CO, ester), 1660 (CO), 1611
(C═N), 1594 (C═C); 1H NMR: d = 1.21 (t, 3H, J =7.5 Hz,
CH2CH3), 2.45 (s, 3H, CH3), 3.75 (s, 3H, OCH3), 3.81 (s, 3H,
OCH3), 4.11 (q, 2H, J = 7.5 Hz, CH2CH3), 5.58 (s, 2H, CH2), (s, 1H,
pyrimidine H-4), 7.14–8.14 (m, 12H, ArH0s); 13C NMR d = 13.14,
17.82, 50.24, 56.30, 58.62, 60.14, 102.22, 110.56, 113.21, 115.41,
118.38, 123.95, 123.99, 126.58, 127.62, 129.42, 130.11, 133.12,
137.92, 142.54, 149.24, 151.28, 153.19, 160.78, 164.78, 174.28;
Anal. Calcd. For C32H27BrN4O6 requires (643.48): C, 59.73; H, 4.23;
Br, 12.42; N, 8.71. Found: C, 59.62; H, 4.38; Br, 12.61; N, 8.52%.
Ethyl 5-benzo[1,3]dioxol-4-yl-3-(5-bromobenzofuran-2-carbonyl)-
7-methyl-1-phenyl-1,5-dihydro-[1,2,4]triazolo[4,3-a]pyrimidine-6-
carboxylate (9f). This compound was obtained as yellow crystals
(acetic acid), yield (77%), mp 142–44ꢁC; IR (KBr): 3098 (CH,
aromatic), 1721 (CO, ester), 1661 (CO), 1615 (C═N), 1594 (C═C);
1H NMR: d = 1.16 (t, 3H, J = 7.5 Hz, CH2CH3), 2.20 (s, 3H, CH3),
4.11 (q, 2H, J = 7.5 Hz, CH2CH3), 5.92 (s, 2H, OCH2O), 6.21 (s, 1H,
pyrimidine H-4), 7.14–8.14 (m, 13H, ArH0s); 13C NMR d = 13.14,
17.82, 50.24, 58.62, 100.87, 108.22, 113.21, 115.41, 118.38, 122.95,
123.99, 126.58, 127.62, 129.42, 130.11, 137.12, 142.54, 147.12,
149.24, 153.28, 154.19, 160.78, 164.78, 174.28; Anal. Calcd. For
C31H23BrN4O6 requires (627.44): C, 59.34; H, 3.69; Br, 12.73; N,
8.93. Found: C, 59.53; H, 3.86; Br, 12.66; N, 9.13%.
Method B.
Equimolar amounts of the appropriate
hydrazonoyl chlorides 4, 10a–h, and sodium ethoxide (0.005
mol each) in ethanol (20 mL) were refluxed for 3 h. The
reaction mixture was cooled, and the resulting solid was
collected and recrystallized from the acetic acid to give products
identical in all aspects (mp, mixed mp, and spectra) with the
corresponding products obtained by method A.
Ethyl 3-(5-bromo-benzofuran-2-carbonyl)-7-methyl-1,5-
diphenyl-1,5-dihydro-[1,2,4]triazolo[4,3-a]pyrimidine-6-
carboxylate (9a). This compound was obtained as red crystals (acetic
acid), yield (82%), mp 185–88ꢁC; IR (KBr): 3098 (CH, aromatic),
1
1718 (CO, ester), 1662 (CO), 1617 (C═N), 1594 (C═C); H NMR:
d =1.23 (t, 3H, J = 7.5 Hz, CH2CH3), 2.57 (s, 3H, CH3), 4.08 (q, 2H,
J = 7.5 Hz, CH2CH3), 6.15 (s, 1H, pyrimidine H-4), 7.14–8.14
(m, 14H, ArH0s); 13C NMR d = 13.25, 17.65, 55.12, 58.62, 101.42,
113.21, 115.41, 118.38, 123.95, 123.99, 126.58, 127.62, 129.42,
130.11, 138.92, 142.54, 149.24, 151.28, 153.19, 159.78, 164.78,
174.58; MS, m/z (%) = 582 (M+, 5.6%), 584 (M+2, 5.6%), 359 (49%),
255 (17%), 222 (23%), 105 (84%), 77 (100%), 65 (32%); Anal. Calcd.
For C30H24N4O4 requires (583.43): C, 71.42; H, 4.79; N, 11.10.
Found: C, 71.28; H, 4.87; N, 11.21%.
Ethyl 3-(5-bromo-benzofuran-2-carbonyl)-7-methyl-1-phenyl-
5-p-tolyl-1,5-dihydro-[1,2,4]triazolo[4,3-a]pyrimidine-6-carboxylate
(9b). This compound was obtained as orange crystals (acetic acid),
yield (80%), mp 162–5ꢁC; IR (KBr): 3098 (CH, aromatic), 1710
1
(CO, ester), 1659 (CO), 1617 (C═N), 1594 (C═C); H NMR: d =
1.23 (t, 3H, J = 7.5 Hz, CH2CH3), 2.21 (s, 3H, CH3), 2.25 (s, 3H,
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Triazolino[4,3-a]pyrimidines, 1,3,4-Thiadiazoles, and 5-Arylazothiazoles
Ethyl 3-(5-bromo-benzofuran-2-carbonyl)-5-(4-isopropylphenyl)-
7-methyl-1-phenyl-1,5-dihydro-[1,2,4]triazolo[4,3-a]pyrimidine-6-
carboxylate (9g). This compound was obtained as yellow crystals
(acetic acid), yield (68%), mp 162–64ꢁC; IR (KBr): 3098
(CH, aromatic), 1700 (CO),1662 (CO), 1615 (C═N), 1594
(C═C); 1H NMR: d = 1.22 (t, 3H, J = 7.5 Hz, CH2CH3), 1.29 (d,
6H, J = 7.5 Hz, ((CH3)2CH), 2.87 (hept., 1H, J = 7.5 Hz, ((CH3)
2CH), 4.02 (q, 2H, J = 7.5 Hz, CH2CH3), 6.08 (s, 1H), 7.16
(d, 1H, ArH), 7.41–7.66 (m, 5H, ArH0s), 7.74 (d, 1H, ArH), 7.91
(d, 2H, J = 8 Hz, ArH), 8.21 (d, 1H, J = 4 ArH), 8.42 (s, 1H,
ArH); 13C NMR d = 13.14, 17.82, 24.24, 33.62, 54.58, 57.68,
101.23, 113.78, 115.21, 118,34, 123.88, 124.12, 126.21, 127.85,
129.57, 129.98, 130.12, 137.15, 142.78, 144.35, 147.84, 149.23,
151.32, 153.41, 160.24, 165.53, 172.85; MS, m/z (%) = 627
(7.2%), 626 (18%), 625 (21.7%), 624 (19.3%), 623 (18.1%), 597
(15%), 595 (15%), 552 (49%), 551 (51%), 550 (48%), 507 (56%),
506 (35%), 505 (76%), 504 (54%), 226 (12%), 225 (91%), 224
(53%), 223 (49%), 169 (43%), 168 (32%), 167 (42%), 166 (33%),
155 (15%), 143 (15%), 128 (30%), 115 (30%), 105 (13%), 77
(100%), 65 (27%); Anal. Calcd. For C33H29BrN4O4 requires
(625.51): C, 63.36; H, 4.67; Br, 12.77; N, 8.96. Found: C, 63.45;
3-(5-Bromo-benzofuran-2-carbonyl)-1-phenyl-5,6,7,8-
tetrahydro-1H-9-thia-1,2,3a,10-tetraaza-cyclopenta[b]fluoren-
4-one (14). This compound was obtained as yellow crystals (DMF),
yield (75%), mp 246–48ꢁC; IR (KBr): 3098 (CH, aromatic), 1662
(CO), 1617 (C═N), 1594 (C═C); 1H NMR: d = 1.61–1.85 (m, 4H),
2.80–2.95 (m, 4H), 7.23 (t, 1H, J = 8 Hz, ArH0s), 7.41 (s, 1H, ArH),
7.42–7.52 (m, 2H, ArH0s), 7.89 (d, 1H, J = 8 Hz, ArH), 8.12 (d, 1H,
J = 8 Hz, ArH), 8.19 (d, 1H, J = 8 Hz, ArH), 8.38 (s, 1H, ArH);
13C NMR d = 21.23, 22.45, 25.43, 27.11, 113.25, 115.78, 123.11,
12345, 123.78, 124.25, 126.45, 127.45, 128.36, 129.15, 131.54,
142.89, 152.25, 154.78, 162.32, 165.18; Anal. Calcd. For
C26H17BrN4O3S requires (545.41): C, 57.26; H, 3.14; Br, 14.65;
N, 10.27; S, 5.88. Found: C, 57.41; H, 2.97; Br, 14.47; N, 10.15,
S, 6.02%.
1-(5-Bromobenzofuran-2-yl)-2-thiocyanatoethanone (15a)
and 1-(5-bromobenzofuran-2-yl)-2-selenocyanatoethanone (15b).
A mixture of 2-bromo-1-(5-bromobenzofuran-2-yl)ethanone (4; 3.15
g, 0.001 mol) and potassium thio/selenacyanate (0.01 mol) in ethanol
(25 mL) was stirred for 4 h. The resulting solid was collected and
recrystallized from ethanol N,N-dimethylformamide gave 15a and
15b, respectively, as a buff crystals.
H, 4.78; Br, 12.91; N, 9.26%.
1-(5-Bromobenzofuran-2-yl)-2-thiocyanatoethanone (15a).
Yield (82%), mp 124–26ꢁC; IR (KBr): 3095 (CH, aromatic), 2990,
Ethyl 3-(5-bromo-benzofuran-2-carbonyl)-5-(1,3-diphenyl-1H-
1
pyrazol-4-yl)-7-methyl-1-phenyl-1,5-dihydro-[1,2,4]triazolo[4,3-a]
pyrimidine-6-carboxylate (9h). This compound was obtained as
yellow crystals (acetic acid), yield (72%), mp 146–48ꢁC; IR
(KBr): 3098 (CH, aromatic), 1700 (CO),1662 (CO), 1615 (C═N),
2947 (CH aliphatic), 2152 (CN), 1665 (CO); H NMR: d = 4.19
(s, 2H), 7.14–7.54 (m, 4H, ArH0s); 13C NMR d = 34.52 (CH2),
110.25, 111.42, 113.84, 115.75, 122.35, 127.45, 131.12, 149.14,
153.75, 182.89; Anal. Calcd. For C11H6BrNO2S requires
(296.14): C, 44.61; H, 2.04; Br, 26.98; N, 4.73; S, 10.81. Found:
C, 44.54; H, 2.12; Br, 26.87; N, 4.64; S, 10.98%.
1
1594 (C═C); H NMR: d = 1.22 (t, 3H, J = 7.5 Hz, CH2CH3),
4.02 (q, 2H, J = 7.5 Hz, CH2CH3), 6.16 (s, 1H), 7.12–7.95 (m, 22
H, ArH0s), 8.12 (s, 1H, pyrazole H-5); 13C NMR d = 13.14,
17.82, 45.58, 59.68, 99.23, 113.78, 115.21, 116.23, 117.46,
118,34, 122.88, 126.21, 127.85, 129.57, 128.48, 129.98, 131.12,
134.15, 135.24, 141.48, 142.78, 144.35, 147.84, 149.23, 153.32,
156.41, 165.53, 175.85; MS, m/z (%) = 627 (707%), 625 (18%),
555 (28%), 552 (15%), 485 (15%), 224 (23%), 223 (30%), 222
(23%), 169 (25%), 167 (30.8%), 166 (30%), 143 (12%), 136
(15%), 93 (38%), 77 (100%), 65 (25%); Anal. Calcd. For
C39H29BrN6O4:requires (724.14): C, 64.56; H, 4.03; Br, 11.01; N,
11.58. Found: C, 64.85; H, 4.16; Br, 11.32; N, 11.72%.
Bromobenzofuran-2-yl)-2-selenocyanatoethanone (15b).
Yield (75%), mp >300ꢁC; IR (KBr): 3098 (CH, aromatic), 2947
(CH aliphatic), 2161 (CN), 1662 (CO); 1H NMR: d = 4.23
(s, 2H), 7.15–7.54 (m, 4H, ArH0s); 13C NMR d = 33.52 (CH2),
102.25, 111.42, 115.84, 118.75, 122.35, 129.45, 148.14, 153.75,
185.89; Anal. Calcd. For C11H6BrNO2Se requires (343.03): C,
38.51; H, 1.76; Br, 23.29; N, 4.08. Found: C, 38.32; H, 1.67; Br,
23.43; N, 4.21%.
1,3,4-Thiadiazoline 17a,b and 1,3,4-selenadiazoline 17c.
Method A. A mixture of 4 (2.11 g, 0.005 mol) and the
appropriate amount of potassium thiocyanate (or potassium
selenocyanate; 0.006 mol) in ethanol (25 mL) was stirred at room
temperature for 4 h. The resulting solid was collected, washed
with water, and crystallized from ethanol to give yellow crystals
17a and 17c, respectively.
Method B. Benzenediazonium chloride (5 mmol), which
prepared from aniline (0.45 mL, 5 mmol), hydrochloric acid (6 N,
6 mL), and sodium nitrite (0.35g, 5 mmol), was added dropwise
with stirring to a cold solution of a mixture of the appropriate
1-(5-bromobenzofuran-2-yl)-2-thiocyanatoethanone (15a) and
1-(5-bromobenzofuran-2-yl)-2-selenocyanatoethanone (15b;
5 mmol) and sodium acetate trihydrate (1.3 g, 10 mmol) in ethanol
(50 mL). The resulting solid was collected and recrystallized from
ethanol to give a product identical in all respects (mp, mixed mp,
and spectral data) with that obtained from method A.
(5-Bromobenzofuran-2-yl)(4,5-dihydro-5-imino-4-phenyl-1,3,4-
thiadiazol-2-yl)methanone (17a). Yield (75%), mp 172–74ꢁC; IR
(KBr): 3291 (NH), 3070 (CH, aromatic), 1640 (CO), 1594 (C═C);
1H NMR: d = 7.57–8.06 (m, ArH0s and NH); 13C NMR d = 113.45,
115.32, 119.78, 124.25, 127.23, 127.74, 129.78, 130.45, 141.78,
143.45, 150.25, 152.78, 154.65, 174.12; Anal. Calcd. For
C17H10BrN3O2S requires (400.25): C, 51.01; H, 2.52; Br, 19.96; N,
10.50; S, 8.01. Found: C, 51.24; H, 2.37; Br, 20.11; N, 10.42; S, 7.76%.
3-(5-Bromo-benzofuran-2-carbonyl)-1-phenyl-1H-[1,2,4]
triazolo[3,4-b]quinazolin-5-one (12). This compound was
obtained as yellow crystals (acetic acid), yield (57%), mp 220–22ꢁC;
IR (KBr): 3069 (CH, aromatic), 2917 (CH, aliphatic), 1662 (CO),
1
1607 (C═N), 1594 (C═C); H NMR: d = 7.50 (t, 1H, J = 6H,
ArH), 7.63–7.70 (m, 8H, ArH0s), 7.89 (d, 1H, J = 8 Hz, ArH), 8.12
(d, 1H, J = 8 Hz, ArH), 8.19 (d, 1H, J = 8 Hz, ArH), 8.38 (d, 1H, J
= 8 Hz, ArH); MS, m/z (%) = 481.6 (52%), 314.8 (85%), 299.4
(66%), 271 (60%), 269 (60%), 228 (57%), 226 (56%), 222 (90%),
210 (71%), 172 (56%), 170 (57%), 62%), 155 (53%), 120 (100%),
111 (82%), 108 (575), 98 (72%); Anal. Calcd. For C24H13BrN4O3
requires (485.29): C, 59.40; H, 2.70; Br, 16.47; N, 11.55. Found: C,
59.12; H, 2.53; Br, 16.68; N, 11.71%.
(5-Bromo-benzofuran-2-yl)-(1-phenyl-1H-benzo[4,5]imidazo
[2,1-c][1,2,4]triazol-3-yl)-methanone (13). This compound was
obtained as yellow crystals (acetic acid), yield (82%), mp
218–21ꢁC; IR (KBr): 3098 (CH, aromatic), 1662 (CO), 1617
(C═N), 1594 (C═C); 1H NMR: d = 7.50 (d, 1H, J = 10 Hz, ArH),
7.63–7.70 (m, 8H, ArH0s), 7.89 (d, 1H, J = 10 Hz, ArH), 8.12
(d, 1H, J = 10 Hz, ArH), 8.19 (d, 1H, J = 10 Hz, ArH), 8.38
(d, 1H, J = 10 Hz, ArH); Anal. Calcd. For C23H13BrN4O2 requires
(457.28): C, 60.41; H, 2.87; Br, 17.47; N, 12.25. Found: C, 60.24;
H, 2.62; Br, 17.31; N, 12.00%.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1104
A. O. Abdelhamid, A. A. Fahmi, and B. S. Baaui
Vol 49
(5-Bromobenzofuran-2-yl)(4,5-dihydro-5-imino-4-p-tolyl-1,3,4-
50.89; H, 2.26; Br, 19.91; N, 6.98; S, 7.99. Found: C, 51.08; H,
2.42; Br, 19.72; N, 6.79; S, 8.22%.
thiadiazol-2-yl)methanone (17b). Yield (72%), mp 186–88ꢁC; IR
(KBr): 3308 (NH), 3098 (CH, aromatic), 1640 (CO), 1594 (C═C);
1H NMR: d = 2.17 (s, 3H, CH3), 7.57–7.92 (m, 8H, ArH0s and
NH protons); 13C NMR d = 19.58, 113.75, 115.92, 119.78,
120.58, 124.25, 127.23, 133.45, 141.58, 144.75, 150.38, 153.28,
154.83, 173.79; Anal. Calcd. For C18H12BrN3O2S requires
(414.28): C, 52.19; H, 2.92; Br, 19.29; N, 10.14; S, 7.74 Found:
C, 51.85; H, 3.21; Br, 19.32; N, 10.25; S, 7.91%.
5-(5-Bromo-benzofuran-2-carbonyl)-3-p-tolyl-3H-[1,3,4]
thiadiazol-2-one (19b). Yield (70%), mp 182–84ꢁC; IR (KBr):
3090 (CH, aromatic), 1693 (CO), 1640 (CO), 1594 (C═C), 1365
(NO); 1H NMR: d = 2.34 (s, 3H, CH3), 7.26–8.03 (m, 8H,
ArH0s); 13C NMR d = 20.85, 113.25, 115.45, 119.45, 119.89,
124.62, 127.25, 130.89, 134.25, 143.58, 150.24, 153.11, 154.75,
171.98; Anal. Calcd. For C18H11BrN2O3S requires (415.26): C,
52.06; H, 2.67; Br, 19.24; N, 6.75; S, 7.72. Found: C, 52.14; H,
2.86; Br, 19.42; N, 6.56; S, 7.60%.
(5-Bromobenzofuran-2-yl)(4,5-dihydro-5-imino-4-phenyl-1,3,4-
selenadiazol-2-yl)methanone (17c). Yield (78%), mp 164–66ꢁC; IR
(KBr): 3209 (NH), 3092 (CH, aromatic), 1640 (CO), 1598 (C═C);
1H NMR: d = 7.68–8.32 (m, ArH0s and NH proton); Anal. Calcd.
For C17H10BrN3O2Se requires (447.14): C, 45.66; H, 2.25; Br,
17.87; N, 9.40.Found: C, 45.86; H, 2.32; Br, 17.68; N, 9.12%.
5-Nitrosoimino-4-substituted 1,3,4-thiad/selenadiazol-2-yl)
methanone 18a–c. A cold saturated solution of sodium nitrite
(10 mL) was added dropwise to a solution of the appropriate
17a–c (1 g) in acetic acid (20 mL) in an ice bath while stirring.
The reaction mixture was stirred for 30 min. The resulting solid
was collected, washed with water, and crystallized from acetone
to give a rosy products 18a–c, respectively.
(5-Bromobenzofuran-2-yl)(4,5-dihydro-5-nitrosoimino-4-phenyl-
1,3,4-thiadiazol-2-yl)methanone (18a). Yield (78%), mp 158–60ꢁC;
IR (KBr): 3098 (CH, aromatic), 1643 (CO), 1594 (C═C), 1360
(NO); 1H NMR: d = 7.57–7.92 (m, ArH0s); 13C NMR d = 112.85,
115.25, 119.89, 124.35, 125.78, 127.25, 127.84, 130.58, 132.48,
142.49, 151.78, 152.45, 154.65, 154.89, 173.45; Anal. Calcd. For
C17H9BrN4O3S requires (429.25): C, 47.57; H, 2.11; Br, 18.61;
N, 13.05; S, 7.47. Found: C, 47.75; H, 2.24; Br, 18.75; N, 13.21;
S, 7.64%.
(5-Bromobenzofuran-2-yl)(4,5-dihydro-5-nitrosoimino-4-p-tolyl-
1,3,4-thiadiazol-2-yl)methanone (18b). Yield (84%), mp 160–62ꢁC;
IR (KBr): 3098 (CH, aromatic), 1662 (CO), 1594 (C═C), 1350 (NO);
1H NMR: d = 2.32 (s, 3H, CH3), 7.57–7.92 (m, 8H, ArH0s); 13C
NMR d = 21.18, 112.85, 115.25, 119.89, 124.35, 127.84, 130.58,
133.48, 134.42, 143.49, 151.78, 152.45, 154.65, 154.89, 173.45;
Anal. Calcd. For C18H11BrN4O3S requires (443.27): C, 48.77; H,
2.50; Br, 18.03; N, 12.64; S, 7.23. Found: C, 48.65; H, 2.32; Br,
18.15; N, 12.46; S, 7.12%.
5-(5-Bromo-benzofuran-2-carbonyl)-3-phenyl-3H-[1,3,4]
selenadiazol-2-one (19c). Yield (68%), mp 176–78ꢁC; IR
(KBr): 3075 (CH, aromatic), 1693 (CO), 1635 (CO), 1594
1
(C═C); H NMR: d = 7.57–7.92 (m, ArH0s); Anal. Calcd. For
C17H9BrN2O3Se requires (448.13): C, 45.56; H, 2.02; Br, 17.83;
N, 6.25. Found: C, 45.75; H, 2.21; Br, 17.71; N, 6.40%.
N-[5-(5-Bromo-benzofuran-2-carbonyl)-3-substituted 3H-
[1,3,4]thia/selenadiazol-2-ylidene]-acetamide
20a–20c. A
mixture of the appropriate 17a–c (1 g) in acetic acid (10 mL) and
acetic anhydride (5 mL) was warmed for 5 min at 70ꢁC. The
reaction mixture was poured onto ice water (40 mL). The solid
was collected and recrystallized from ethanol to give the N-acetyl
derivatives 20a–c, respectively, as a pale yellow crystals.
N-[5-(5-Bromo-benzofuran-2-carbonyl)-3-phenyl-3H-[1,3,4]
thiadiazol-2-ylidene]-acetamide (20a). Yield (88%), mp 240–
42ꢁC; IR (KBr): 3108 (CH, aromatic), 2923 (CH aliphatic), 1643
(CH3CON═), 1594 (C═C), 1362 (CH3); 1H NMR: d = 2.27 (s, 3H,
CH3), 7.26–8.05 (m, 9H, ArH0s); Anal. Calcd. For C19H12BrN3O3S
requires (442.29): C, 51.60; H, 2.73; Br, 18.07; N, 9.50; S, 7.25.
Found: C, 51.58; H, 2.55; Br, 18.17; N, 9.72; S, 7.14%.
N-[5-(5-Bromo-benzofuran-2-carbonyl)-3-p-tolyl-3H-[1,3,4]
thiadiazol-2-ylidene]-acetamide (20b). Yield (80%), mp 218–
20; IR (KBr): 3108 (CH, aromatic), 2923 (CH aliphatic), 1643
1
(CH3CON═), 1594 (C═C), 1362 (CH3); H NMR: d = 2.22 (s,
3H, CH3), 2.34 (s, 3H, CH3), 7.57–7.92 (m, 8H, ArH0s); Anal.
Calcd. For C20H14BrN3O3S requires (456.31): C, 52.64; H, 3.09;
Br, 17.51; N, 9.21; S, 7.03. Found: C, 52.38; H, 3.12; Br, 17.73;
N, 9.05; S, 7.18%.
N-[5-(5-Bromo-benzofuran-2-carbonyl)-3-phenyl-3H-[1,3,4]
selenadiazol-2-ylidene]-acetamide (20c). Yield (75%), mp 251–
53ꢁC; IR (KBr): 3098 (CH, aromatic), 1640 (CO), 1594 (C═C); 1H
NMR: d = 2.23 (s, 3H, CH3), 7.57–7.92 (m, 9H, ArH0s); Anal.
Calcd. For C19H12BrN3O3Se requires (489.18): C, 46.65; H, 2.47;
Br, 16.33; N, 8.59; Se, 16.14. Found: C, 46.86; H, 2.65; Br, 16.12;
N, 8.87%.
N-[5-(5-Bromo-benzofuran-2-carbonyl)-3-substituted 3H-
[1,3,4]thia/selenadiazol-2-ylidene] benzamide 21a–c. Benzoyl
chloride (1 mL) was added to a solution of the appropriate 17a–c
(0.5 g) in pyridine (15 mL), and the mixture was refluxed for 10
min, then poured onto ice water (50 mL) then acidified with
hydrochloric acid. The resulting product was collected and washed
several times with boiling water. The solid was recrystallized from
ethanol to give yellow crystals.
(5-Bromobenzofuran-2-yl)(4,5-dihydro-5-nitrosoimino-4-phenyl-
1,3,4-selenadiazol-2-yl)methanone (18c). Yield (68%), mp 176–
78ꢁC; IR (KBr): 3093 (CH, aromatic), 1642 (CO), 1594 (C═C),
1
1355 (NO); H NMR: d = 7.57–7.92 (m, ArH0s); Anal. Calcd. For
C17H9BrN4O3Se requires (476.14): C, 42.88; H, 1.91; Br, 16.78; N,
11.77. Found: C, 42.92; H, 2.22; Br, 16.87; N, 11.65%.
5-(5-Bromo-benzofuran-2-carbonyl)-3-substituted 3H-[1,3,4]
thiadiazol-2-one 19a and 19b and 5-(5-bromo-benzofuran-2-
carbonyl)-3-phenyl-3H-[1,3,4]selenadiazol-2-one 19c.
A
solution of the appropriate 18a–c (0.5 g) in xylene (20 mL) was
refluxed for 15 min. The solvent was evaporated under reduced
pressure. The residual oil was triturated with petroleum ether
(40–60ꢁC), and the solid formed was collected and recrystallized
from ethanol to give a yellow crystals of 1,3,4-thiadiazolinone
19a,b and 1,3,4-selenadiazolinone 19c, respectively.
N-[5-(5-Bromo-benzofuran-2-carbonyl)-3-phenyl-3H-[1,3,4]
thiadiazol-2-ylidene]-benzamide (21a). Yield (78%), mp 228–
30ꢁC; IR (KBr): 3098 (CH, aromatic), 1639 (CO), 1594 (C═C);
5-(5-Bromo-benzofuran-2-carbonyl)-3-phenyl-3H-[1,3,4]
thiadiazol-2-one (19a). Yield (75%), mp 184–86ꢁC; IR (KBr):
1
3098 (CH, aromatic), 1693 (CO), 1640 (CO), 1594 (C═C); H
1H NMR:
d =
7.57–7.92 (m, ArH0s); Anal. Calcd. For
NMR: d = 7.57–7.92 (m, ArH0s); MS, m/z (%) = 402 (M+2,
21%), 400 (M+, 21%), 340 (20%), 338 (20%), 223, 100%), 221
(100%), 167 (42%), 169 (42%), 144 (17%), 117 (10%), 88 (23%),
77 (17%); Anal. Calcd. For C17H9BrN2O3S requires (401.23): C,
C24H14BrN3O3S requires (504.36): C, 57.15; H, 2.80; Br, 15.84;
N, 8.33; S, 6.36. Found: C, 57.24; H, 2.95; Br, 15.72; N, 8.12; S,
6.47%.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

September 2012
Reaction with Hydrazonoyl Halides 64: Synthesis of Some New
1105
Triazolino[4,3-a]pyrimidines, 1,3,4-Thiadiazoles, and 5-Arylazothiazoles
N-[5-(5-Bromo-benzofuran-2-carbonyl)-3-phenyl-3H-[1,3,4]
thiadiazol-2-ylidene]-4-methyl-benzamide (21b). Yield (75%),
mp 268–88ꢁC; IR (KBr): 3090 (CH, aromatic), 1645 (CO),
5-(2-p-Tolyldiazenyl)-4-(5-bromobenzofuran-2-yl)thiazol-
2-amine (25b). Yield (68%), mp 240–42ꢁC; IR (KBr): 3210,
2180 (NH2), 3098 (CH, aromatic), 1620 (C═N), 1596
(C═C); 1H NMR: d = 2.42 (s, 3H, CH3C6H4), 4.25 (s, br.,
2H, NH2) 7.57–7.92 (m, 8H, ArH0s); 13C NMR d = 21.23,
99.78, 104.25, 110.28, 114.24, 116.32, 122.48, 125.23,
127.24, 129.57, 131.28, 136.78, 145.21, 153.45, 156.32,
168.54; Anal. Calcd. For C18H13BrN4OS requires (413.29):
C, 52.31; H, 3.17; Br, 19.33; N, 13.56; S, 7.76. Found: C,
52.45; H, 3.28; Br, 19.55; N, 13.68; S, 7.57.
1
1594 (C═C); H NMR: d = 2.42 (s, 3H, CH3), 7.57–7.92 (m,
9H, ArH0s); 13C NMR d = 19.88, 113.23, 115.45, 119.25,
119.78, 124.56, 127.46, 128.45, 129.23, 131.78, 132.87,
134.25, 136.49, 144.25, 146.31, 151.23, 152.48, 154.34,
173.25, 174.28; Anal. Calcd. For C25H16BrN3O3S requires
(518.38): C, 57.92; H, 3.11; Br, 15.41; N, 8.11; S, 6.19. Found:
C, 58.12; H, 3.25; Br, 15.27; N, 8.23; S, 6.00%.
N-[5-(5-Bromo-benzofuran-2-carbonyl)-3-phenyl-3H-[1,3,4]
selenadiazol-2-ylidene]-benzamide (21c). Yield (70%), mp
223–26ꢁC; IR (KBr): 3098 (CH, aromatic), 1639 (CO), 1594
4-(5-Bromobenzofuran-2-yl)thiazol-2-amine (26). A mixture
of 2 (3.03 g, 0.01 mol) and thiourea (0.46 g, 0.006 mol) in ethanol
(25 mL) was heated under reflux for 2 h. The reaction mixture was
poured onto ice cold water (100 mL) and few drops of ammonium
hydroxide. The resulting solid was collected, washed with water,
and crystallized from ethanol to give yellow crystals (ethanol),
yield (77%), mp 218–20ꢁC; IR (KBr): 3098 (CH, aromatic), 1625
1
(C═C); H NMR: d = 7.57–7.92 (m, ArH0s); Anal. Calcd. For
C24H14BrN3O3Se requires (550.94): C, 52.29; H, 2.56; Br, 14.50;
N, 7.62; Se, 14.32. Found: C, 52.41; H, 2.32; Br, 14.74; N, 7.83%.
2-(5-Bromo-benzofuran-2-carbonyl)-3-thia-1,4,9b-triaza-
cyclopenta[a]naphthalen-5-one (22a) and 2-(5-bromo-benzofuran-
2-carbonyl)-3-selena-1,4,9b-triaza-cyclopenta[a]naphthalen-5-one
(22b). Diazotization of anthranilic acid or methyl anthranilate was
added dropwise with stirring to a cold solution of a mixture of the
appropriate 1-(5-bromobenzofuran-2-yl)-2-thiocyanatoethanone (15a)
and 1-(5-bromobenzofuran-2-yl)-2-selenocyanatoethanone (15b; 1.81
g, 5 mmol) and sodium acetate trihydrate (1.3 g, 10 mmol) in
ethanol (50 mL). The resulting solid was collected and recrystallized
from N,N-dimethylformamide to give yellow crystals 22a and 22b,
respectively.
1
(C═N), 1594 (C═C); H NMR: d = 4.25 (s, br., 2H, NH2) 7.57–
7.92 (m, 4H, ArH0s); MS, m/z (%) = 296 (100%), 294 (100%), 254
(24%), 252 (22%), 225 (17%), 223 (15%), 182 (14%), 180 (14%),
145 (74%), 107 (18%), 93 (10%); Anal. Calcd. For C11H7BrN2OS
requires (295.16): C, 44.76; H, 2.39; Br, 27.07; N, 9.49; S, 10.86.
Found: C, 44.67; H, 2.45; Br, 27.15; N, 9.58; S, 10.67%.
Thiadiazolines 31a–n and (5-bromo-1-benzofuran-2-yl)[4-
phenyl-5-(phenylimino)-4,5-dihydro-1,3,4-thiadiazol-2-yl]
methanone (32). Triethylamine (0.75 mL, 0.005 mol) was added
dropwise with stirring to a mixture of the appropriate alkyl
carbodithioates 27a–n, 28a,b, or methyl phenylcarbamodithioate
(0.005 mol) and compound 4 (1.8 g, 0.005 mol) in ethanol (20
mL). The resulting solid, which formed after 30 min, was
collected and recrystallized from the proper solvent and gave the
corresponding thiadiazolines 31a–n and 32, respectively, in a
good yield.
2-(5-Bromo-benzofuran-2-carbonyl)-3-thia-1,4,9b-triaza-
cyclopenta[a]naphthalen-5-one (22a). Yield (75%), mp 326–28ꢁC;
IR (KBr): 3066 (CH, aromatic), 1643 (CO), 1596 (C═C); 1H NMR: d
= 7.71–8.67 (m, ArH0s); MS, m/z (%) = 427 (M+2), 52%, 427 (M+),
55%),225 (87%), 223 (74%)169 (43%), 167 (55%); Anal. Calcd. For
C18H8BrN3O3S requires (426.24): C, 50.72; H, 1.89; Br, 18.75; N,
9.86; S, 7.52. Found: C, 50.52; H, 2.10; Br, 18.47; N, 9.68; S, 7.45%.
2-(5-Bromo-benzofuran-2-carbonyl)-3-selena-1,4,9b-triaza-
cyclopenta[a]naphthalen-5-one (22b). Yield (70%), mp >300ꢁC;
IR (KBr): 3098 (CH, aromatic), 1780 (CO), 1658 (CO), 1594
[5-(Benzylidenehydrazono)-4-phenyl-4,5-dihydro-[1,3,4]
thiadiazol-2-yl]-(5-bromo-benzofuran-2-yl)-methanone (31a). This
compound was obtained as red crystals (dioxan), yield (70%),
mp 245–48ꢁC; IR (KBr): 3098 (CH, aromatic), 1650 (CO),
1625 (C═N), 1594 (C═C); 1H NMR: d = 7.24 (t, 1H, J = 8 Hz,
ArH), 7.58 (t, 1H, J = 8 Hz, ArH), 7.72–7.92 (m, H, ArH0s),
8.32 (s, 1H, CH vinyl); MS, m/z (%) = 504 (100.0%), 502
(97.3%), 279 (38%), 222 (100%), 162 (23%), 118 (17%), 77
(27%); Anal. Calcd. For C24H15BrN4O2S requires (503.37): C,
57.27; H, 3.00; Br, 15.87; N, 11.13; S, 6.37. Found: C, 57.32;
H, 2.86; Br, 15.78; N, 11.25; S, 6.43%.
(5-Bromo-benzofuran-2-yl)-[4-phenyl-5-(thien-2-
ylmethylenehydrazono)-4,5-dihydro-[1,3,4]thiadiazol-2-yl]-
methanone (31b). This compound was obtained as yellow
crystals (dioxan), yield (73%), mp 229–32ꢁC; IR (KBr): 3075
(CH, aromatic), 1648 (CO), 1620 (C═N), 1594 (C═C); 1H NMR:
d = 7.05 (t, 1H, J = 8 Hz, thiophene H-3), 7.24 (t, 1H, J = 8 Hz,
ArH), 7.33 (d, 2H, thiophene H-2 and H-4), 7.57–7.92 (m,
9H, ArH0s and CH═, vineyl); Anal. Calcd. For
C22H13BrN4O2S2 requires (509.4): C, 51.87; H, 2.57; Br,
15.69; N, 11.00; S, 12.59 Found: C, 51.78; H, 2.75; Br,
15.86; N, 11.12; S, 12.68%.
1
(C═C); H NMR: d = 7.57–7.92 (m, ArH0s); Anal. Calcd. For
C18H8BrN3O3Se requires (473.14): C, 45.69; H, 1.70; Br, 16.89;
N, 8.88. Found: C, 45.84; H, 1.95; Br, 16.67; N, 9.00%.
5-(2-Phenyldiazenyl)-4-(5-bromobenzofuran-2-yl)thiazol-2-
Method A. A mixture of 4 (2.11 g, 0.005 mol) and
amine (25)
thiourea (0.46 g, 0.006 mol) in ethanol (25 mL) was stirred at
room temperature for 4 h. The resulting solid was collected,
washed with water, and crystallized from ethanol to give 25a.
Method B. Arenediazonium chloride (5 mmol), which prepared
from aromatic amines (5 mmol), hydrochloric acid (6 N, 6 mL), and
sodium nitrite (0.35g, 5 mmol), was added dropwise with stirring to
a cold solution of a mixture of 4-(5-bromobenzofuran-2-yl)thiazol-
2-amine (26; 1.81 g, 5 mmol) and sodium acetate trihydrate
(1.3 g, 10 mmol) in ethanol (50 mL). The resulting solid was
collected and recrystallized from ethanol to give red crystals
25a and 25b.
5-(2-Phenyldiazenyl)-4-(5-bromobenzofuran-2-yl)thiazol-2-
amine (25a). Yield (75%), mp 228–30ꢁC; IR (KBr): 3210, 2180
(NH2), 3098 (CH, aromatic), 1625 (C═N), 1594 (C═C); 1H
NMR: d = 4.12 (s, br., 2H, NH2) 7.57–7.92 (m, 9H, ArH0s);
MS, m/z (%) = 400 (100.0%), 398 (98.0%), 399 (18.2%), 401
(17.8%), 229 (26%), 105 (57%), 77 (100%), 65 (28%); Anal.
Calcd. For C17H11BrN4OS requires (399.26): C, 51.14; H,
2.78; Br, 20.01; N, 14.03; S, 8.03. Found: C, 51.25; H, 2.87;
Br, 20.22; N, 14.13; S, 8.25%.
(5-Bromo-benzofuran-2-yl)-[5-(furan-2-ylmethylenehydrazono)-
4-phenyl-4,5-dihydro-[1,3,4]thiadiazol-2-yl]-methanone (31c).
This compound was obtained as yellow crystals (dioxan), yield
(61%), mp 235–38ꢁC; IR (KBr): 3140 (CH, vinyl), 3057 (CH,
1
aromatic), 1650 (CO), 1618 (C═N), 1596 (C═C); H NMR: d =
6.35 (t, 1H, J = 8 Hz, furan H-3), 7.25 (t, 1H, J = 8 Hz, ArH),
7.70–7.92 (m, 10H, ArH0s); Anal. Calcd. For C22H13BrN4O3S
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1106
A. O. Abdelhamid, A. A. Fahmi, and B. S. Baaui
Vol 49
requires (493.33): C, 53.56; H, 2.66; Br, 16.20; N, 11.36; S, 6.50.
Found: C, 53.45; H, 2.71; Br, 16.10; N, 11.41; S, 6.57%.
(5-Bromobenzofuran-2-yl)-[4-phenyl-5-(pyridin-4-
ylmethylenehydrazono)-4,5-dihydro-[1,3,4]thiadiazol-2-yl]-
ArH0s); 13C NMR: d = 15.23, 110.89, 111.45, 115.28, 118.76,
124.25, 128.78, 127.16, 127.86, 130.15, 131.41, 143.25, 144.75,
145.94, 150.57, 152.72, 153.23, 154.75, 158.21, 174.54; Anal.
Calcd. For C23H15BrN4O3S requires (507.36): C, 54.45; H, 2.98;
Br, 15.75; N, 11.04; S, 6.32. Found: C, 54.54; H, 2.98; Br, 15.57;
N, 11.25; S, 6.32%.
(5-Bromo-benzofuran-2-yl)-{4-phenyl-5-[(1-pyridin-2-yl-
ethylidene)-hydrazono]-4,5-dihydro-[1,3,4]thiadiazol-2-yl}-
methanone (31j). This compound was obtained as red crystals
(dioxan), yield (98%), mp 216–18ꢁC; IR (KBr): 3098 (CH,
aromatic), 1639 (CO), 1612 (C═N), 1596 (C═C); 1H NMR:
d = 2.50 (s, 3H, CH3), 7.57–7.92 (m, 11H, ArH0s), 8.58 (d, 1H,
J = 8 Hz, ArH0s), 8.73 (d, 1H, J = 8 Hz, ArH0s); Anal. Calcd. For
C24H16BrN5O2S requires (518.39): C, 55.61; H, 3.11; Br, 15.41;
N, 13.51; S, 6.19. Found: C, 55.52; H, 3.31; Br, 15.23; N, 13.68;
S, 6.32%.
2-{[5-(5-Bromo-benzofuran-2-carbonyl)-3-phenyl-3H-[1,3,4]
thiadiazol-2-ylidene]-hydrazono}-indan-1,3-dione (31k). This
compound was obtained as brown crystals (ethanol), yield (69%),
mp 152–55ꢁC; IR (KBr): 3098 (CH, aromatic), 1728 (CO), 1685
(CO), 1635 (CO), 1618 (C═N), 1589 (C═C); 1H NMR: d = 7.22–
7.25 (t, 1H, J = 9 Hz, ArH), 7.65–8.03 (m, 10H, ArH0s), 8.50 (t,
1H, ArH); Anal. Calcd. For C26H13BrN4O4S requires (557.37): C,
56.03; H, 2.35; Br, 14.34; N, 10.05; S, 5.75. Found: C, 56.15; H,
2.43; Br, 14.52; N, 10.18; S, 5.84%.
5-[(5-Bromo-1-benzofuran-2-yl)carbonyl]-3-phenyl-1,3,4-
thiadiazol-2(3H)-one cyclopentylidenehydrazone (31l). This
compound was obtained as orange crystals (AcOH), yield
(75%), mp 206–208ꢁC; IR (KBr): 3098 (CH, aromatic),
1643 (CO), 1574 (C═C); 1H NMR: d = 1.83 (pent, 4H,
methanone (31d).
This compound was obtained as yellow
crystals (dioxan), yield (63%), mp 228–30ꢁC; IR (KBr): 3098
(CH vinyl), 3055 (CH, aromatic), 1648 (CO), 1615 (C═N), 1590
(C═C); 1H NMR: d = 7.21 (t, 1H, J = 8 Hz, ArH), 7.60–7.93 (m,
10, ArH0s), 8.25 (s, 1H, vinyl), 8.24 (d, 2H, J = 8 Hz, ArH0s);
Anal. Calcd. For C23H14BrN5O2S requires (504.36): C, 54.77; H,
2.80; Br, 15.84; N, 13.89; S, 6.36. Found: C, 54.65; H, 2.68; Br,
15.92; N, 13.98; S, 6.46%.
(5-Bromo-benzofuran-2-yl)-{5-[(4-isopropyl-benzylidene)
hydrazono]-4-phenyl-4,5-dihydro-[1,3,4]thiadiazol-2-yl}-methanone
(31e). This compound was obtained as yellow crystals (AcOH),
yield (70%), mp 207–10ꢁC; IR (KBr): 3085 (CH, aromatic), 1639
(CO), 1608 (C═N), 1594 (C═C); 1H NMR: d = 1.26 (d, 6H, J = 7
Hz, (CH3)2CH), 2.95 (hept, 1H, J = 7 Hz, (CH3)2CH), 7.26–8.15
(m, 13H, ArH0s), 8.42 (s, 1H, vinyl CH═N); 13C NMR d = 24.35,
33.58, 113.25, 115.04, 119.48, 124.45, 126.25, 127.28, 128.45,
130.28, 130.58, 131.87, 147.28, 150.35, 151.65, 153.48, 154.75,
158.92, 173.45; Anal. Calcd. For C27H21BrN4O2S requires
(545.45): C, 59.45; H, 3.88; Br, 14.65; N, 10.27; S, 5.88. Found:
C, 59.54; H, 3.72; Br, 14.56; N, 10.35; S, 5.80%.
[5-(Benzo[1,3]dioxol-4-ylmethylenehydrazono)-4-phenyl-4,5-
dihydro-1,3,4]-thiadiazol-2-yl]-(5-bromo-benzofuran-2-yl)-
methanone (31f).
This compound was obtained as orange
crystals (ethanol), yield (82%), mp 211–14ꢁC; IR (KBr): 3072
(CH, aromatic), 1640 (CO), 1620 (C═N), 1596 (C═C); 1H NMR:
d = 6.01 (s, 2H, OCH2O), 7.13–7.26 (m, 4H, ArH0s and CH═N),
7.63–7.93 (m, 9H, ArH0s); 13C NMR: d = 101.12, 113.45, 115.28,
117.85, 118.45, 119.39, 121.28, 122.40, 124.12, 124.75, 127.56,
130.12, 130.75, 142.10, 147.82, 150.54, 152.16, 152.78, 153.87,
154.62, 162.88, 174.24; Anal. Calcd. For C25H15BrN4O4S requires
(547.38): C, 54.86; H, 2.76; Br, 14.60; N, 10.24; S, 5.86. Found:
C, 54.68; H, 2.67; Br, 14.72; N, 10.42; S, 5.60%.
J
= 7 Hz, CH2CH2CH2), 2.59 (t, 4H, J = 7 Hz,
CH2CH2CH2), 7.26–8.12 (m, 9H, ArH0s); Anal. Calcd. For
C22H17BrN4O2S requires (481.36): C, 54.89; H, 3.56; Br,
16.60; N, 11.64; S, 6.66. Found: C, 54.95; H, 3.65; Br,
16.48; N, 11.45; S, 6.78%.
5-[(5-Bromo-1-benzofuran-2-yl)carbonyl]-3-phenyl-1,3,4-
thiadiazol-2(3H)-one cyclohexylidenehydrazone (31m). This
compound was obtained as orange crystals (AcOH), yield
(97%), mp 194–97ꢁC; IR (KBr): 3098 (CH, aromatic), 1635
(5-Bromo-benzofuran-2-yl)-{4-phenyl-5-[(1-phenyl-ethylidene-
hydrazono]-4,5-dihydro-[1,3,4]thiadiazol-2-yl}-methanone (31g).
This compound was obtained as yellow crystals (dioxan), yield
(75%), mp 234–37ꢁC; IR (KBr): 3098 (CH, aromatic), 1650
(CO), 1625 (C═N), 1594 (C═C); 1H NMR: d = 2.35 (s, 3H,
CH3), 7.22–7.93 (m, 14H, ArH0s); 13C NMR d = 14.42, 113.25,
115.45, 119.67, 124.25, 126.23, 126.37, 127.12, 127.78, 128.16,
129.45, 130.58, 140.21, 144.58, 146.25, 150.23, 152.56, 154.38,
173.89; Anal. Calcd. For C25H17BrN4O2S requires (517.4): C,
58.03; H, 3.31; Br, 15.44; N, 10.83; S, 6.20. Found: C, 58.03; H,
3.31; Br, 15.44; N, 10.83; S, 6.20%.
(5-Bromo-benzofuran-2-yl)-{4-phenyl-5-[(1-thien-2-yl-
ethylidene)hydrazono]-4,5-dihydro-[1,3,4]thiadiazol-2-yl}-
methanone (31h). This compound was obtained as yellow
crystals (dioxan), yield (69%), mp 232–35ꢁC; IR (KBr): 3098
(CH, aromatic), 1650 (CO), 1625 (C═N), 1594 (C═C); 1H NMR:
d = 2.39 (s, 3H, CH3), 7.16–8.17 (m, 12H, ArH0s); Anal. Calcd.
For C23H15BrN4O2S2 requires (523.42): C, 52.78; H, 2.89; Br,
15.27; N, 10.70; S, 12.25. Found: C, 52.87; H, 2.98; Br, 15.35; N,
10.54; S, 12.15%.
1
(CO), 1569 (C═C); H NMR: d = 1.68 (m, 4H), 2.46 (m, 4H),
2.66 (m, 2H), 7.26–8.12 (m, 9H, ArH0s; Anal. Calcd. For
C23H19BrN4O2S requires (495.39): C, 55.76; H, 3.87; Br, 16.13;
N, 11.31; S, 6.47. Found: C, 55.67; H, 3.87; Br, 16.34; N,
11.44; S, 6.56%.
5-[(5-Bromo-1-benzofuran-2-yl)carbonyl]-3-phenyl-1,3,4-
thiadiazol-2(3H)-one cycloheptylidenehydrazone (31n). This
compound was obtained as orange (AcOH), yield (96%), mp
205–207ꢁC; IR (KBr): 3098 (CH, aromatic), 1643 (CO), 1574
(C═C); 1H NMR: d = 1.83 (m, 2H), 2.06 (m, 4H), 2.58 (m,
6H), 7.57–7.92 (m, 9H, ArH0s); Anal. Calcd. For
C24H21BrN4O2S requires (509.42): C, 56.59; H, 4.16; Br,
15.69; N, 11.00; S, 6.29. Found: C, 56.65; H, 4.25; Br, 15.78;
N, 11.22; S, 6.45%.
(5-Bromo-1-benzofuran-2-yl)[4-phenyl-5-(phenylimino)-4,5-
dihydro-1,3,4-thiadiazol-2-yl]methanone (32). This compound was
obtained as red crystals (AcOH), yield (84%), mp 203–206ꢁC; IR
(KBr): 3098 (CH, aromatic), 1635 (CO), 1569 (C═C); 1H NMR: d
= 6.98 (m, 1H, ArH), 7.20–7.36 (m, 5H, ArH0s), 6.65–6.73
(m, 6H, ArH0s), 7.88–7.93 (4H, ArH0s); Anal. Calcd. For
C23H14BrN3O2S requires (476.35): C, 57.99; H, 2.96; Br, 16.77;
N, 8.82; S, 6.73. Found: C, 58.09; H, 2.85; Br, 16.66; N, 8.92;
S, 6.65%.
(5-[(5-Bromo-1-benzofuran-2-yl)carbonyl]-3-phenyl-1,3,4-
thiadiazol-2(3H)-one [1-(2-furyl)ethylidene]hydrazone
(31i).
This compound was obtained as red crystals (dioxan),
yield (76%), mp 220–23ꢁC; IR (KBr): 3097 (CH, aromatic), 1639
(CO), 1612 (C═N), 1594 (C═C); 1H NMR: d = 2.35 (s, 3H,
CH3), 6.35 (t, 1H, J = 5Hz, furan H-3), 7.27–7.93 (m, 11H,
Journal of Heterocyclic Chemistry
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September 2012
Reaction with Hydrazonoyl Halides 64: Synthesis of Some New
1107
Triazolino[4,3-a]pyrimidines, 1,3,4-Thiadiazoles, and 5-Arylazothiazoles
[9] Howlett, D. R.; Perry, A. E.; Godfrey, F.; Swatton, J. E.;
Jennings, K. H.; Spitzfaden, C.; Wadsworth, H.; Wood, S. J.; Markwell,
R. E. Biochem J 1999, 340, 283.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet