Synthesis of new 1-phenylthieno[1,2,4]triazolo[4,3-a]pyrimidin-5(4H)-one derivatives

Article abstract of DOI:10.1002/jhet.549

A series of novel 1-phenylthieno[1,2,4]triazolo[4,3-a]pyrimidin-5(4H)-one derivatives 5 and 6 were synthesized by oxidative cyclization of thienopyrimidinonyl hydrazones using iodobenzene diacetate.

Full text of DOI:10.1002/jhet.549

May 2011
Synthesis of New 1-Phenylthieno[1,2,4]triazolo[4,3-a]pyrimidin-
5(4H)-one Derivatives
597
Yang-Heon Song* and Hoon Young Son
Department of Chemistry, Mokwon University, Daejeon 302-729, South Korea
*E-mail: yhsong@mokwon.ac.kr
Received March 16, 2010
DOI 10.1002/jhet.549
Published online 7 March 2011 in Wiley Online Library (wileyonlinelibrary.com).
A series of novel 1-phenylthieno[1,2,4]triazolo[4,3-a]pyrimidin-5(4H)-one derivatives 5 and 6 were
synthesized by oxidative cyclization of thienopyrimidinonyl hydrazones using iodobenzene diacetate.
J. Heterocyclic Chem., 48, 597 (2011).
INTRODUCTION
RESULTS AND DISCUSSION
The heterocyclic compounds containing 1,2,4-triazole
nucleus have attracted considerable interest for many
years due to their diverse biological activities, such as
antifungal, bactericidal, antitumor, and anti-inflamatory
agents [1–4]. Futhermore, it has been noticed that intro-
duction of an additional ring to the triazolopyrimidine
system which is one of the fused 1,2,4-triazole com-
pound tends to exert profound influence in conferring
new biological activities in these molecules. Recently,
thienotriazolopyrimidinone 1 and pyrazolotriazolopyri-
midine 2 derivatives of tricyclic heterocyclic compounds
(five-six-five ring systems) as shown in Figure 1 have
been explored for xanthine oxidase inhibitor, and adeno-
sine A1/A2A or A2A/A3 receptor antagonists, respectively
[5,6]. And, triazoloquinazolinone 3 and its analogs were
known to have antibacterial and H1-antihistaminic activ-
ity [7,8]. Similar analogues based on the substituted
thieno[3,2-e]triazolopyrimidinone moiety were also
reported [9]. We have recently designed and synthesized
a series of thienotriazolopyrimidine compounds 4 of
potential biological interest using iodobenzene diacetate
[10].
Compound 5 and 6 were prepared according to
Scheme 1. The key intermediate 2-thioxo-2,3-dihydro-
thieno[3,2-d]pyrimidin-4(1H)-one (11) and 2-thioxo-2,3-
dihydrothieno[2,3-d]pyrimidin-4(1H)-one (12) were syn-
thesized respectively from the amino esters 7 and 8 with
ammonium thiocyanate and benzoyl chloride in acetone
at reflux, with subsequent heating of the resultant thienyl
benzoylthioureas 9 and 10 with an ethanolic potassium
hydroxide solution and acidification [12]. The spectro-
scopic data and elemental analyses are in agreement
with the assigned structures of new compounds 9, 10,
11, and 12. The methylation of 11 and 12 with methyl
iodide and aqueous sodium hydroxide afforded methyl-
thio derivatives 13 and 14 which upon nucleophilic dis-
placement of the methylthio group with hydrazine gave
the respective hydrazine derivatives 15 and 16. Conden-
sation of 15 and 16 with appropriate aromatic aldehydes
in ethanol containing a few drops of piperidine fur-
nished the corresponding arylhydrazones 17 and 18. The
oxidative cyclization of the latter compounds to final
products 5 and 6 was respectively achieved using iodo-
benzene diacetate in good yields [10]. For instance,
when a solution of 17a or 18a in dichloromethane was
treated with 1.2 equiv of iodobenzene diacetate at room
temperature, the only one product was obtained as solid
within 1 h. The crude product was filtered and purified
by recrystallization to give pure compound 1-phenyl-
thieno [2,3-e][1,2,4]triazolo[4,3-a]pyrimidin-5(4H)-one
(5a) or 1-phenylthieno[3,2-e][1,2,4]triazolo[4,3-a]pyri-
midin-5(4H)-one (6a) in 62–66% yield. The structure of
these compounds was confirmed by elemental analysis,
As a continuation of our works for biologically active
thienopyridine or thienopyrimidine derivatives [11] we
now describe the synthesis of new 1-phenylthieno[2,3-
e][1,2,4]triazolo[4,3-a]pyrimidin-5(4H)-one derivatives
(5) and 1-phenylthieno[3,2-e][1,2,4]triazolo[4,3-a]pyri-
midin-5(4H)-one derivatives (6), which are structurally
related to 1 and 3 as one of tricyclic skeleton in the
hope of obtaining compounds of diverse pharmaceutical
activities.
C
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Y.-H. Song and H. Y. Son
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doublets at 6.63 and 7.94 for thiophene protons (H-8
and H-7), multiplet signals at 7.70–7.57 for aromatic
protons and singlet at 12.75 for NH group, while 6a
showed two doublets at 7.21 and 7.39 for thiophene pro-
tons (H-6 and H-7), multiplet signals at 7.68–7.55 for
aromatic protons and singlet at 8.82 for NH. It is note-
worthy that the b proton (H-8) of thiophene in 5a
appeared at d 6.63 in higher field, whereas the b proton
(H-7) of 15 or 17a was found to appear at d 7.01ꢀ7.10
in more down field. This may be attributed to the
through-space anisotropic effect of the phenyl group on
this proton in 5a.
As shown in Scheme 2, the oxidative cyclization of
the hydrazone derivatives, 17 and 18, toward two nitro-
gen atoms, N(1) or N(3), may provide two kinds of
structural isomers, angular triazole compounds or linear
triazole compounds or a mixture of both. To provide a
decisive evidence for the assigned structure of 5 and 6,
an authentic sample of 5a was prepared by an alterna-
tive synthesis (Scheme 3) and compared with the prod-
uct isolated from the oxidative cyclization of 17a. The
synthetic strategy for authentic 5a was based on oxida-
tive cyclization of the hydrazone 17A protected with
benzyl group at N(3) atom to exclusively afford the
angular compound. In this route, 7 was reacted with
Figure 1. Heterocyclic compounds containing 1,2,4-triazole.
1H NMR and IR spectra. IR spectra of compound 5a
and 6a revealed absorption bands at 3436–3430 cmꢀ1
for NH, 1662–1660 cmꢀ1 for CO. The mass spectral
data of these compounds showed same molecular ion
peak at m/z ¼ 268 with very similar fragmentation pat-
tern, and also showed ion at m/z ¼ 152 which could be
attributed to the loss of NAN¼¼C-phenyl from the mo-
1
lecular ion. The H NMR spectrum of 5a showed two
Scheme 1. Synthesis of 5 and 6. Reagents and conditions: (i) NH4NCS, C6H5COCl, acetone, reflux; (ii) KOH, EtOH, reflux; H2O, HCl, rt; (iii)
MeI, 2N NaOH, rt; (iv) NH2NH2 hydrate, EtOH, reflux; (v) PhCHO, piperidine, EtOH, reflux; (vi) PhI(OAc)2, dichloromethane, rt.
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Synthesis of New 1-Phenylthieno[1,2,4]triazolo[4,3-a]pyrimidin-5(4H)-one Derivatives
599
Scheme 2. Two possible ways for the oxidative cyclization of thieno-
pyrimidinonyl hydrazone 17.
Me4Si as internal standard and chemical shifts are given in
ppm (d). IR spectra were recorded using an EXCALIBUR
FTS-3000 FTIR spectrophotometer. Electron ionization mass
spectra were recorded on a HP 59580 B spectrometer. Elemen-
tal analyses were performed on a Carlo Erba 1106 elemental
analyzer.
General procedure for the preparation of
9 and
10. Benzoyl chloride (5.6 mL, 48 mmol) was added dropwise
to a solution of ammonium thiocyanate (5.2 g, 68 mmol) in an
anhydrous acetone (40 mL). The reaction mixture was refluxed
for 30 min, and then a solution of amino ester 7 or 8 (48
mmol) in anhydrous acetone (60 mL) was added. The resulting
solution was kept at reflux for 2 h and filtered while hot. After
cooling and evaporation of the solvent, the solid product was
purified by recrystallization from ethanol.
Methyl 3-(3-benzoylthioureido)thiophene-2-carboxylate (9). The
compound was obtained from 7 in 75% yield, mp 159–160ꢁC;
1H NMR (dimethyl sulfoxide-d6): d 13.7 (s, 1H, NH), 11.7 (s,
1H, NH), 8.53 (d, J ¼ 5.8 Hz, 1H, H-5, thiophene), 7.97 (d,
2H, Ar), 7.92 (d, J ¼ 5.8 Hz, 1H, H-4, thiophene), 7.63 (t, 1H,
Ar), 7.52 (t, 2H, Ar), 3.85 (s, 3H), ms: (m/z) 320 (Mþ). Anal.
benzyl isothiocyanate to give 11A, which was methyl-
ated with dimethyl sulfate to afford 13A. Treatment of
13A with hydrazine hydrate gave 15A, and the reaction
of the latter with benzaldehyde to yield the hydrazone
17A. The oxidative cyclization of 17A with iodobenzene
diacetate, and the subsequent deprotection of benzyl
group in 19A gave 5a. This was identical in all respects
Scheme 3. Alternative synthesis of 5a. Reagents and conditions: (i)
C6H5CH2NCS, EtOH, reflux; (ii) KOH, EtOH, reflux; H2O, HCl, rt;
(iii) (CH3)2SO4, NaOH, EtOH, reflux; (iv) NH2NH2 hydrate, EtOH,
reflux; (v) PhCHO, piperidine, EtOH, reflux; (vi) PhI(OAc)2, dichloro-
methane, rt; (vii) H2/Pd, HCl, DMF, rt.
1
(mp, IR, H NMR, and MS spectra) with 5a obtained
from the oxidative cyclization of 17a. In a similar man-
ner the assigned structure 6a was also confirmed by its
comparison with an authentic sample, which was pre-
pared by the same method as depicted in Scheme 3.
This finding indicates that 5a has angular structure, not
linear structure, and that both 5 and 6 were prepared
unambiguously by regioselective cyclization as outlined
in Scheme 1. This result is consistent with one reported
in a recent report, which was regioselective cyclization
of aldehyde N-[6-benzyl-5(4H)-as-triazinon-3-yl]hydra-
zones [13].
In conclusion, we have reported the synthesis of new
phenylthieno[2,3-e][1,2,4]triazolo[4,3-a]pyrimidin-5(4H)-
one derivatives (5) and phenyl thieno[3,2-e][1,2,4] tria-
zolo[4,3-a]pyrimidin-5(4H)-one derivatives (6) with
potential biological activities by oxidative cyclization of
thienopyrimidinonyl hydrazones.
EXPERIMENTAL
Melting points were determined in capillary tubes on Bu¨chi
apparatus and are uncorrected. Each compound of the reactions
was checked on thin-layer chromatograpohy of Merck Kiesel-
gel 60F254 and purified by column chromatograpohy Merck
1
silica gel (70–230 mesh). The H NMR spectra were recorded
on Bruker DRX-300 FT NMR spectrometer (300 MHz) with
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Y.-H. Song and H. Y. Son
Vol 48
Calcd. for C14H12N2O3S2: C, 52.48; H, 3.78, N, 8.74. Found:
C, 52.60; H, 3.59; N, 8.88.
and hydrazine hydrate (15 mL) in absolute ethanol (20 mL)
was refluxed for 72 h. After cooling, the solid products formed
were filtered, dried, and recrystallized from ethanol.
Ethyl 2-(3-benzoylthioureido)thiophene-3-carboxylate (10). The
compound was obtained from 8 in 70% yield, mp 174–
175ꢁC;1H NMR (dimethyl sulfoxide-d6): d 14.5 (s, 1H, NH),
11.9 (s, 1H, NH), 7.98 (d, 2H, Ar), 7.64 (t, 1H, Ar), 7.53 (t,
2H, Ar), 7.32 (d, J ¼ 5.8 Hz, 1H, H-5, thiophene), 7.12 (d, J
¼ 5.8 Hz, 1H, H-4, thiophene), ms: (m/z) 334 (Mþ). Anal.
Calcd. for C15H14N2O3S2: C, 53.87; H, 4.22, N, 8.38. Found:
C, 53.69; H, 4.04; N, 8.57.
General procedure for the preparation of 11 and 12. To
a hot potassium hydroxide solution (1.2 g, 21.4 mmol) in abso-
lute ethanol (50 mL) was added the thienylthiourea 9 or 10
(12 mmol), and the mixture was refluxed for 2 h. The suspen-
sion was filtered while hot and the solid washed with hot etha-
nol to give the corresponding product of potassium salt. The
product suspended in water (60 mL) was acidified with con-
centrated hydrochloric acid, and the mixture was stirred at
room temperature for 1 h. The solid was collected by filtration
and purified by recrystallization from ethanol.
2-Hydrazinothieno[3,2-d]prrimidin-4(3H)-one (15). The
compound was obtained from 13 in 72% yield, mp 352–
1
353ꢁC; H NMR (dimethyl sulfoxide-d6): d 8.95 (bs, 1H, NH),
7.91 (d, J ¼ 5.8 Hz, 1H, H-6, thiophene), 7.01 (d, J ¼ 5.8 Hz,
1H, H-7, thiophene), 2.48 (bs, 2H, NH2), ms: m/z (%) 182
(Mþ, 96), 168 (48), 152 (100), 125 (85), 97 (22). Anal. Calcd.
for C7H6N2OS2: C, 42.40; H, 3.05, N, 14.13. Found: C, 42.58;
H, 3.13; N, 14.30.
2-Hydrazinothieno[2,3-d]prrimidin-4(3H)-one (16). The
compound was obtained from 14 in 66% yield, mp 236–
1
237ꢁC; H NMR (dimethyl sulfoxide-d6): d 8.45 (bs, 1H, NH),
7.09 (d, J ¼ 5.8 Hz, 1H, H-6, thiophene), 7.01 (d, J ¼ 5.8 Hz,
1H, H-5, thiophene), 2.50 (bs, 2H, NH2), ms: m/z (%) 182
(Mþ, 90), 166 (40), 151 (66), 125 (44). Anal. Calcd. for
C7H6N2OS2: C, 42.40; H, 3.05, N, 14.13. Found: C, 42.22; H,
3.16; N, 14.01.
General procedure for the preparation of 17a-h and
18a-h. A mixture of the hydrazine 15 or 16 (10 mmol) and
the appropriate aldehyde (10 mmol) in absolute ethanol
(30 mL) containing a few drops of piperidine was refluxed for
3 h. After cooling, the solid products formed were filtered,
dried, and recrystallized from ethanol.
(E)-2-(2-Benzylidenehydrazinyl)thieno[3,2-d]pyrimidin-4(3H)-
one (17a). Yield 78%, mp 297–299ꢁC; 1H NMR (dimethyl
sulfoxide-d6): d 11.57 (bs, 2H, NH), 8.02 (m, 2H, imine proton
and H-6, thiophene), 7.94 (m, 2H, H-20 and H-60, phenyl),
7.40(m, 3H, H-30, H-40 and H-50, phenyl), 7.10 (d, J ¼ 5.8 Hz,
1H, H-7, thiophene), ms: m/z (%) 270 (Mþ, 65), 193 (39), 167
(100), 125 (42). Anal. Calcd. for C13H10N4OS: C, 57.76; H,
3.73, N, 20.73. Found: C, 57.92; H, 3.62; N, 20.59.
2-Thioxo-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-one (11). The
compound was obtained from 9 in 65% yield, mp 341–343ꢁC;
IR(KBr) 3120 and 3075 (NH), 1670 (C¼¼O) cmꢀ1
;
1H NMR
(dimethyl sulfoxide-d6): d 13.2 (s, 1H, NH), 12.5 (s, 1H, NH),
8.16 (d, J ¼ 5.8 Hz, 1H, H-6, thiophene), 7.03 (d, J ¼ 5.8 Hz,
1H, H-7, thiophene), ms: (m/z) 184 (Mþ). Anal. Calcd. for
C6H4N2OS2: C, 39.11; H, 2.19, N, 15.20. Found: C, 39.30; H,
2.03; N, 15.46.
2-Thioxo-2,3-dihydrothieno[2,3-d]pyrimidin-4(1H)-one (12). The
compound was obtained from 9 in 60% yield, mp 305–307ꢁC;
IR(KBr) 3110 and 3080 (NH), 1675 (C¼¼O) cmꢀ1
;
1H NMR
(dimethyl sulfoxide-d6): d 13.4 (s, 1H, NH), 12.4 (s, 1H, NH),
7.26 (d, J ¼ 5.8 Hz, 1H, H-6, thiophene), 7.19 (d, J ¼ 5.8 Hz,
1H, H-5, thiophene), ms: (m/z) 184 (Mþ). Anal. Calcd. for
C6H4N2OS2: C, 39.11; H, 2.19, N, 15.20. Found: C, 39.25; H,
2.30; N, 15.09.
(E)-2-(2-(4-Chlorobenzylidene)hydrazinyl)thieno[3,2-d]pyri-
1
midin-4(3H)-one (17b). Yield 82%, mp 315–317ꢁC; H NMR
(dimethyl sulfoxide-d6): d 11.75 (bs, 2H, NH), 8.02 (m, 4H,
imine proton, H-6, H-20 and H-60), 7.43 (d, 2H, H-30 and H-
50), 7.11 (d, J ¼ 5.8 Hz, 1H, H-7), ms: m/z (%) 304 (Mþ, 32),
193 (34), 167 (100), 126 (30). Anal. Calcd. for C13H9ClN4OS:
C, 51.23; H, 2.98, N, 18.38. Found: C, 51.01; H, 3.09; N,
18.49.
(E)-2-(2-(4-Methoxybenzylidene)hydrazinyl)thieno[3,2-d]pyri-
midin-4(3H)-one (17c). Yield 69%, mp 261–263ꢁC; 1H NMR
(dimethyl sulfoxide-d6): d 11.47 (bs, 2H, NH), 8.02 (d, J ¼
5.8 Hz, 1H, H-6), 7.98 (s, 1H, imine proton), 7.88 (d, 2H, H-20
and H-60), 7.08 (d, J ¼ 5.8 Hz, 1H, H-7), 6.95 (d, 2H, H-30
and H-50), 3.78 (s, 3H, OMe), ms: m/z (%) 300 (Mþ, 41), 167
(100), 126 (28). Anal. Calcd. for C14H12N4O2S: C, 55.99; H,
4.03, N, 18.65. Found: C, 56.13; H, 3.91; N, 18.49.
(E)-2-(2-(4-Bromobenzylidene)hydrazinyl)thieno[3,2-d]pyr-
imidin-4(3H)-one (17d). Yield 65%, mp 323–325ꢁC; 1H
NMR (dimethyl sulfoxide-d6): d 11.67 (bs, 2H, NH), 8.02 (d, J
¼ 5.8 Hz, 1H, H-6), 7.99 (s, 1H, imine proton), 7.92 (d, 2H,
H-20 and H-60), 7.58 (d, 2H, H-30 and H-50), 7.09 (d, J ¼ 5.8
Hz, 1H, H-7), ms: m/z (%) 349 (Mþ, 33), 193 (34), 167 (100),
126 (35). Anal. Calcd. for C13H9BrN4OS: C, 44.71; H, 2.60,
N, 16.04. Found: C, 44.84; H, 2.51; N, 16.22.
General procedure for the preparation of 13 and 14. To
a cooling solution of the thioxo derivative 11 or 12 (5.4
mmol) in 2N sodium hydroxide solution (20 mL) at 5ꢁC was
added methyl iodide (2.50 g, 16.2 mmol), and the mixture was
refluxed for 2 h. The precipitates were collected by filtration,
dissolved in hot water and neutralized with 10% hydrochloric
solution. The solid obtained was filtered, washed with water,
dried, and recrystallized from ethanol.
2-(Methylthio)thieno[3,2-d]pyrimidin-4(3H)-one (13). The
compound was obtained from 1ꢀ11 in 71% yield, mp 286–
287ꢁC; IR(KBr) 1685 (C¼¼O) cm
;
1H NMR (dimethyl sulf-
oxide-d6): d 12.7 (s, 1H, NH), 7.41 (d, J ¼ 5.8 Hz, 1H, H-6,
thiophene), 7.28 (d, J ¼ 5.8 Hz, 1H, H-7, thiophene), 2.52 (s,
3H, Me), ms: (m/z) 198 (Mþ). Anal. Calcd. for C7H6N2OS2:
C, 42.40; H, 3.05, N, 14.13. Found: C, 42.58; H, 3.13; N,
14.30.
2-(Methylthio)thieno[2,3-d]pyrimidin-4(3H)-one (14). The
compound was obtained from 12 in 69% yield, mp 241–242ꢁC;
1
IR(KBr) 1680 (C¼¼O) cmꢀ1; H NMR (dimethyl sulfoxide-d6):
d 12.8 (s, 1H, NH), 8.12 (d, J ¼ 5.8 Hz, 1H, H-6, thiophene),
7.29 (d, J ¼ 5.8 Hz, 1H, H-5, thiophene), 2.53 (s, 3H, Me), ms:
(m/z) 198 (Mþ). Anal. Calcd. for C7H6N2OS2: C, 42.40; H,
3.05, N, 14.13. Found: C, 42.21; H, 3.16; N, 13.96.
(E)-2-(2-(4-Methylbenzylidene)hydrazinyl)thieno[3,2-d]pyri-
1
midin-4(3H)-one (17e). Yield 58%, mp 263–265ꢁC; H NMR
General procedure for the preparation of 15 and 16. A
mixture of methylthiothienopyrimidinone 13 or 14 (3 mmol)
(dimethyl sulfoxide-d6): d 11.67 (bs, 2H, NH), 8.00 (m, 2H,
imine proton and H-6), 7.80 (d, 2H, H-20 and H-60), 7.19 (d,
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2H, H-30 and H-50), 7.08 (d, J ¼ 5.8 Hz, 1H, H-7), 2.32 (s,
3H, Me), ms: m/z (%) 284 (Mþ, 62), 193 (25), 167 (100), 126
(30). Anal. Calcd. for C14H12N4OS: C, 59.14; H, 4.25, N,
19.70. Found: C, 59.30; H, 4.19; N, 19.88.
(E)-2-(2-(3-Chlorobenzylidene)hydrazinyl)thieno[3,2-d]pyri-
midin-4(3H)-one (17f). Yield 64%, mp 296–298ꢁC; 1H NMR
(dimethyl sulfoxide-d6): d 11.77 (bs, 2H, NH), 8.26 (s, 1H,
imine proton), 8.03 (d, J ¼ 5.8 Hz, 1H, H-6), 8.00 (s, 1H, H-
20), 7.73 (d, 1H, H-60), 7.40 (m, 2H, H-40 and H-50), 7.09 (d, J
¼ 5.8 Hz, 1H, H-7), ms: m/z (%) 304 (Mþ, 55), 193 (20), 167
(100), 126 (26). Anal. Calcd. for C13H9ClN4OS: C, 51.23; H,
2.98, N, 18.38. Found: C, 51.11; H, 3.07; N, 18.50.
(E)-2-(2-(4-Methylbenzylidene)hydrazinyl)thieno[2,3-d]pyri-
1
midin-4(3H)-one (18e). Yield 50%, mp 283–285ꢁC; H NMR
(dimethyl sulfoxide-d6): d 11.52 (bs, 2H, NH), 8.00 (s, 1H,
imine proton), 7.83 (d, 2H, H-20 and H-60), 7.19 (m, 3H, H-30,
H-50 and H-6), 7.08 (d, J ¼ 5.8 Hz, 1H, H-5), 2.32 (s, 3H,
Me), ms: m/z (%) 284 (Mþ, 80), 193 (45), 167 (100), 126
(51). Anal. Calcd. for C14H12N4OS: C, 59.14; H, 4.25, N,
19.70. Found: C, 58.98; H, 4.16; N, 19.84.
(E)-2-(2-(3-Chlorobenzylidene)hydrazinyl)thieno[2,3-d]pyri-
midin-4(3H)-one (18f). Yield 60%, mp 285–287ꢁC; 1H NMR
(dimethyl sulfoxide-d6): d 11.75 (bs, 2H, NH), 8.27 (s, 1H,
imine proton), 8.01 (s, 1H, H-20), 7.73 (d, 1H, H-60), 7.40 (m,
2H, H-40 and H-50), 7.20 (d, J ¼ 5.8 Hz, 1H, H-6), 7.10 (d, J
¼ 5.8 Hz, 1H, H-5), ms: m/z (%) 304 (Mþ, 40), 193 (22), 167
(100), 126 (20). Anal. Calcd. for C13H9ClN4OS: C, 51.23; H,
2.98, N, 18.38. Found: C, 51.40; H, 3.11; N, 18.56.
(E)-2-(2-(3-Bromobenzylidene)hydrazinyl)thieno[3,2-d]pyri-
1
midin-4(3H)-one (17g). Yield 68%, mp 286–288ꢁC; H NMR
(dimethyl sulfoxide-d6): d 11.72 (bs, 2H, NH), 8.36 (s, 1H,
imine proton), 8.03 (d, J ¼ 5.8 Hz, 1H, H-6), 7.99 (s, 1H, H-20),
7.79 (d, 1H, H-60), 7.53 (d, 1H, H-40), 7.34 (t, 1H, H-50), 7.09
(d, J ¼ 5.8 Hz, 1H, H-7), ms: m/z (%) 349 (Mþ, 42), 193 (40),
167 (100), 126 (39). Anal. Calcd. for C13H9BrN4OS: C, 44.71;
H, 2.60, N, 16.04. Found: C, 44.60; H, 2.72; N, 16.17.
(E)-2-(2-(3-Bromobenzylidene)hydrazinyl)thieno[2,3 -d]pyr-
1
imidin-4(3H)-one (18g). Yield 60%, mp 285–287ꢁC; H NMR
(dimethyl sulfoxide-d6): d 11.80 (bs, 2H, NH), 8.37 (s, 1H,
imine proton), 7.98 (s, 1H, H-20), 7.78 (d, 1H, H-60), 7.53 (d,
1H, H-40), 7.34 (t, 1H, H-50), 7.20 (d, J ¼ 5.8 Hz, 1H, H-6),
7.10 (d, J ¼ 5.8 Hz, 1H, H-5), ms: m/z (%) 349 (Mþ, 55),
193 (44), 167 (100), 126 (48). Anal. Calcd. for C13H9BrN4OS:
C, 44.71; H, 2.60, N, 16.04. Found: C, 44.84; H, 2.76; N,
16.11.
(E)-2-(2-(3-Methylbenzylidene)hydrazinyl)thieno[3,2-d]pyri-
1
midin-4(3H)-one (17h). Yield 55%, mp 235–237ꢁC; H NMR
(dimethyl sulfoxide-d6): d 11.55 (bs, 2H, NH), 8.02 (d, J ¼
5.8 Hz, 1H, H-6), 8.00 (s, 1H, imine proton), 7.77 (s, 1H, H-
20), 7.67 (d, 1H, H-60), 7.53 (t, 1H, H-50), 7.17 (d, 1H, H-40),
7.09 (d, J ¼ 5.8 Hz, 1H, H-7), 2.34 (s, 3H, Me), ms: m/z (%)
284 (Mþ, 50), 193 (28), 167 (100), 126 (32). Anal. Calcd. for
C14H12N4OS: C, 59.14; H, 4.25, N, 19.70. Found: C, 58.98; H,
4.15; N, 19.86.
(E)-2-(2-Benzylidenehydrazinyl)thieno[2,3-d]pyrimidin-4(3H)-
one (18a). Yield 68%, mp 281–283ꢁC; 1H NMR (dimethyl
sulfoxide-d6): d 11.58 (bs, 2H, NH), 8.03 (s, 1H, imine pro-
ton), 7.96 (m, 2H, phenyl), 7.38 (m, 3H, phenyl), 7.19 (d, J ¼
5.8 Hz, 1H, H-6, thiophene), 7.09 (d, J ¼ 5.8 Hz, 1H, H-5,
thiophene), ms: m/z (%) 270 (Mþ, 100), 193 (41), 167 (95),
125 (76). Anal. Calcd. for C13H10N4OS: C, 57.76; H, 3.73, N,
20.73. Found: C, 57.88; H, 3.82; N, 20.60.
(E)-2-(2-(3-Methylbenzylidene)hydrazinyl)thieno[2,3 -d]pyr-
1
imidin-4(3H)-one (18h). Yield 50%, mp 274–276ꢁC; H NMR
(dimethyl sulfoxide-d6): d 11.53 (bs, 2H, NH), 8.00 (s, 1H,
imine proton), 7.78 (s, 1H, H-20), 7.68 (d, 1H, H-60), 7.27 (t,
1H, H-50), 7.22–7.16 (m, 2H, H-40 and H-6), 7.09 (d, J ¼ 5.8
Hz, 1H, H-5), 2.34 (s, 3H, Me), ms: m/z (%) 284 (Mþ, 95),
193 (65), 167 (100), 126 (58). Anal. Calcd. for C14H12N4OS:
C, 59.14; H, 4.25, N, 19.70. Found: C, 59.34; H, 4.36; N,
19.89.
General procedure for the preparation of 5 and 6. To a
solution of 17a-h or 18a-h (0.01 mole) in dry dichloromethane
(20 mL), iodobenzene diacetate (0.012 mole) was slowly
added. The reaction mixture was stirred for 1 h at room tem-
perature. After evaporation the precipitate was filtered and
recrystallized from a mixture of chloroform and ethanol.
1-Phenylthieno[2,3-e][1,2,4]triazolo[4,3-a]pyrimidin-5(4H)-
one (5a). Yield 62%, mp 265–267ꢁC; IR (KBr) 3436, 1660
(E)-2-(2-(4-Chlorobenzylidene)hydrazinyl)thieno[2,3-d]pyri-
1
midin-4(3H)-one (18b). Yield 73%, mp 310–312ꢁC; H NMR
(dimethyl sulfoxide-d6): d 11.68 (bs, 2H, NH), 8.00 (m, 3H,
imine proton, H-20 and H-60), 7.45 (d, 2H, H-30 and H-50),
7.19 (d, J ¼ 5.8 Hz, 1H, H-6), 7.09 (d, J ¼ 5.8 Hz, 1H, H-5),
ms: m/z (%) 304 (Mþ, 53), 193 (38), 167 (83), 125 (100).
Anal. Calcd. for C13H9ClN4OS: C, 51.23; H, 2.98, N, 18.38.
Found: C, 51.40; H, 3.12; N, 18.53.
1
cmꢀ1; H NMR (dimethyl sulfoxide-d6): d 12.75 (bs, 1H, NH),
7.94 (d, J ¼ 5.8 Hz, 1H, thiophene, H-7), 7.70–7.63 (m, 2H,
phenyl, H-20 and H-60), 7.61–7.57 (m, 3H, H-30, H-40 and H-
50), 6.63 (d, J ¼ 5.8 Hz, 1H, H-8), ms: m/z (%) 268 (Mþ,
100), 152 (40), 110 (31), 96 (20), 84 (37), 77 (30), 66 (31),
57(45). Anal. Calcd. for C13H8N4OS: C, 55.20; H, 3.01, N,
20.88. Found: C, 55.39; H, 3.19; N, 20.73.
(E)-2-(2-(4-Methoxybenzylidene)hydrazinyl)thieno[2,3-d]pyri-
midin-4(3H)-one (18c). Yield 60%, mp 263–265ꢁC; 1H NMR
(dimethyl sulfoxide-d6): d 11.48 (bs, 2H, NH), 7.98 (s, 1H,
imine proton), 7.88 (d, 2H, H-20 and H-60), 7.17 (d, J ¼ 5.8
Hz, 1H, H-6), 7.07 (d, J ¼ 5.8 Hz, 1H, H-5), 6.95 (d,þ2H, H-
30 and H-50), 3.78 (s, 3H, OMe), ms: m/z (%) 300 (M , 100),
167 (93), 125 (75), 77 (20). Anal. Calcd. for C14H12N4O2S: C,
55.99; H, 4.03, N, 18.65. Found: C, 56.19; H, 3.94; N, 18.73.
(E)-2-(2-(4-Bromobenzylidene)hydrazinyl)thieno[2,3-d]pyri-
1-(4-Chlorophenyl)thieno[2,3-e][1,2,4]triazolo[4,3-a] pyra-
midin-5(4H)-one (5b). Yield 70%, mp 289–291ꢁC; IR (KBr)
3430, 1662 cmꢀ1 1H NMR (dimethyl sulfoxide-d6): d 12.02
;
(bs, 1H, NH), 7.93 (d, J ¼ 5.8 Hz, 1H, thiophene, H-7), 7.71
(d, 2H, phenyl, H-20 and H-60), 7.67 (d, 2H, H-30 and H-50),
6.72 (d, J ¼ 5.8 Hz, 1H, H-8), ms: m/z (%) 302 (Mþ, 66),
152 (78), 125 (33), 84 (79), 66 (99), 57(20). Anal. Calcd. for
C13H7ClN4OS: C, 51.58; H, 2.33, N, 18.51. Found: C, 51.40;
H, 2.41; N, 18.70.
1
midin-4(3H)-one (18d). Yield 60%, mp 296–298ꢁC; H NMR
(dimethyl sulfoxide-d6): d 11.87 (bs, 2H, NH), 8.00 (s, 1H,
imine proton), 7.93 (d, 2H, H-20 and H-60), 7.58 (d, 2H, H-30
and H-50), 7.19 (d, J ¼ 5.8 Hz, 1H, H-6), 7.09 (d, J ¼ 5.8 Hz,
1H, H-5), ms: m/z (%) 349 (Mþ, 46), 193 (35), 167 (100), 125
(64). Anal. Calcd. for C13H9BrN4OS: C, 44.71; H, 2.60, N,
16.04. Found: C, 44.60; H, 2.69; N, 16.17.
1-(4-Methoxyphenyl)thieno[2,3-e][1,2,4]triazolo[4,3-a] pyr-
amidin-5(4H)-one (5c). Yield 66%, mp 299–301ꢁC; IR (KBr)
3430, 1663 cmꢀ1 1H NMR (dimethyl sulfoxide-d6): d 11.32
;
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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Y.-H. Song and H. Y. Son
Vol 48
(bs, 1H, NH), 7.73 (d, J ¼ 5.8 Hz, 1H, thiophene, H-7), 7.61
(d, 2H, phenyl, H-20 and H-60), 7.08 (d, 2H, H-30 and H-50),
6.87 (d, J ¼ 5.8 Hz, 1H, H-8), 3.93 (s, 3H, OMe), ms: m/z
(%) 298 (Mþ, 66), 161 (24), 151 (21), 130 (28), 110 (20), 97
(30), 84 (70), 73 (41), 58 (55). Anal. Calcd. for C14H10N4O2S:
C, 56.37; H, 2.41, N, 18.78. Found: C, 56.22; H, 2.51; N,
18.93.
1-(4-Chlorophenyl)thieno[3,2-e][1,2,4]triazolo[4,3-a] pyra-
midin-5(4H)-one (6b). Yield 72%, mp 396–398ꢁC; IR (KBr)
3420, 1664 cmꢀ1 1H NMR (dimethyl sulfoxide-d6): d 9.12
;
(bs, 1H, NH), 7.75 (d, 2H, phenyl, H-20 and H-60), 7.65 (d,
2H, H-30 and H-50), 7.37 (d, J ¼ 5.8 Hz, 1H, thiophene, H-7),
7.25 (d, J ¼ 5.8 Hz, 1H, H-6), ms: m/z (%) 302 (Mþ, 10),
152 (8), 125 (7), 84 (100), 66 (99). Anal. Calcd. for
C13H7ClN4OS: C, 51.58; H, 2.33, N, 18.51. Found: C, 51.69;
H, 2.40; N, 18.67.
1-(4-Bromophenyl)thieno[2,3-e][1,2,4]triazolo[4,3-a] pyra-
midin-5(4H)-one (5d). Yield 69%, mp 323–325ꢁC; IR (KBr)
3433, 1660 cmꢀ1 1H NMR (dimethyl sulfoxide-d6): d 10.90
;
1-(4-Methoxyphenyl)thieno[3,2-e][1,2,4]triazolo[4,3-a] pyr-
amidin-5(4H)-one (6c). Yield 60%, mp 388–390ꢁC; IR (KBr)
(bs, 1H, NH), 7.78–7.74 (m, 3H, thiophene, H-7 and phenyl,
H-20 and H-60), 7.60 (d, 2H, H-30 and H-50), 6.75 (d, J ¼ 5.8
Hz, 1H, H-8), ms: m/z (%) 347 (Mþ, 15), 200 (21), 183 (30),
152 (19), 129 (16), 97 (22), 84 (91), 73 (40), 66 (100), 57
(62). Anal. Calcd. for C13H7BrN4OS: C, 44.97; H, 2.03, N,
16.14. Found: C, 44.89; H, 2.12; N, 16.30.
3436, 1660 cmꢀ1 1H NMR (dimethyl sulfoxide-d6): d 11.60
;
(bs, 1H, NH), 7.61 (d, 2H, phenyl, H-20 and H-60), 7.36 (d, J
¼ 5.8 Hz, 1H, thiophene, H-7), 7.26 (d, J ¼ 5.8 Hz, 1H, H-6),
7.16 (d, 2H, H-30 and H-50), 3.85 (s, 3H, OMe), ms: m/z (%)
298 (Mþ, 10), 149 (22), 84 (81), 66 (99). Anal. Calcd. for
C14H10N4O2S: C, 56.37; H, 2.41, N, 18.78. Found: C, 56.45;
H, 2.50; N, 18.89.
1-p-Tolylthieno[2,3-e][1,2,4]triazolo[4,3-a]pyramidin-5(4H)-
one (5e). Yield 58%, mp 265–267ꢁC; IR (KBr) 3435, 1662
1
cmꢀ1; H NMR (dimethyl sulfoxide-d6): d 11.20 (bs, 1H, NH),
1-(4-Bromophenyl)thieno[3,2-e][1,2,4]triazolo[4,3-a] pyra-
midin-5(4H)-one (6d). Yield 59%, mp 386–388ꢁC; IR (KBr)
8.08 (d, J ¼ 5.8 Hz, 1H, thiophene, H-7), 7.58 (d, 2H, phenyl,
H-20 and H-60), 7.42 (d, 2H, H-30 and H-50), 6.63 (d, J ¼ 5.8
Hz, 1H, H-8), 2.43 (s, 1H, Me), ms: m/z (%) 282 (Mþ, 14),
152 (11), 129 (10), 97 (10), 84 (82), 73 (10), 66 (100), 57
(15). Anal. Calcd. for C14H10N4OS: C, 59.56; H, 3.57, N,
19.85. Found: C, 59.69; H, 3.70; N, 19.98.
3430, 1662 cmꢀ1 1H NMR (dimethyl sulfoxide-d6): d 8.10
;
(bs, 1H, NH), 7.81 (d, 2H, phenyl, H-20 and H-60), 7.66 (d,
2H, H-30 and H-50), 7.37 (d, J ¼ 5.8 Hz, 1H, thiophene, H-7),
7.27 (d, J ¼ 5.8 Hz, 1H, H-6), ms: m/z (%) 347 (Mþ, 8), 152
(9), 100 (10), 84 (65), 66 (100). Anal. Calcd. for
C13H7BrN4OS: C, 44.97; H, 2.03, N, 16.14. Found: C, 45.15;
H, 2.10; N, 16.26.
1-(3-Chlorophenyl)thieno[2,3-e][1,2,4]triazolo[4,3-a] pyra-
midin-5(4H)-one (5f). Yield 65%, mp 396–399ꢁC; IR (KBr)
3430, 1663 cmꢀ1 1H NMR (dimethyl sulfoxide-d6): d 10.72
;
1-p-Tolylthieno[3,2-e][1,2,4]triazolo[4,3-a]pyramidin-5(4H)-
one (6e). Yield 61%, mp > 400ꢁC; IR (KBr) 3430, 1662
(bs, 1H, NH), 7.88 (d, J ¼ 5.8 Hz, 1H, thiophene, H-7), 7.74
(s, 1H, phenyl, H-20), 7.67–7.59 (m, 3H, phenyl, H-40, H-50
and H-60), 6.76 (d, J ¼ 5.8 Hz, 1H, H-8), ms: m/z (%) 302
(Mþ, 33), 152 (19), 129 (12), 97 (20), 84 (82), 66 (95), 57
(48). Anal. Calcd. for C13H7ClN4OS: C, 51.58; H, 2.33, N,
18.51. Found: C, 51.69; H, 2.24; N, 18.68.
1
cmꢀ1; H NMR (dimethyl sulfoxide-d6): d 8.84 (bs, 1H, NH),
7.54 (d, 2H, phenyl, H-20 and H-60), 7.42 (d, 2H, H-30 and H-
50), 7.35 (d, J ¼ 5.8 Hz, 1H, thiophene, H-7), 7.21 (d, J ¼ 5.8
Hz, 1H, H-6), 2.41 (s, 1H, Me), ms: m/z (%) 282 (Mþ, 11),
152 (8), 129 (10), 100 (25), 84 (62), 66 (100). Anal. Calcd. for
C14H10N4OS: C, 59.56; H, 3.57, N, 19.85. Found: C, 59.66; H,
3.44; N, 20.02.
1-(3-Bromophenyl)thieno[2,3-e][1,2,4]triazolo[4,3-a] pyra-
midin-5(4H)-one (5g). Yield 71%, mp > 400ꢁC; IR (KBr)
3435, 1660 cmꢀ1 1H NMR (dimethyl sulfoxide-d6): d 12.32
;
1-(3-Chlorophenyl)thieno[3,2-e][1,2,4]triazolo[4,3-a] pyra-
midin-5(4H)-one (6f). Yield 70%, mp > 400ꢁC; IR (KBr)
(bs, 1H, NH), 7.88–7.83 (m, 2H, thiophene, H-7 and phenyl,
H-20), 7.78 (d, 1H, H-60), 7.68 (d, 1H, H-40), 7.53 (t, 1H, H-
50), 6.77 (d, J ¼ 5.8 Hz, 1H, H-8), ms: m/z (%) 347 (Mþ, 20),
200 (19), 183 (30), 152 (20), 97 (30), 84 (95), 73 (39), 66
(100), 57 (69). Anal. Calcd. for C13H7BrN4OS: C, 44.97; H,
2.03, N, 16.14. Found: C, 45.10; H, 2.10; N, 16.03.
3433, 1663 cmꢀ1 1H NMR (dimethyl sulfoxide-d6): d 10.34
;
(bs, 1H, NH), 7.80 (s, 1H, phenyl, H-20), 7.69–7.65 (m, 2H,
phenyl, H-40 and H-60), 7.61 (t, 1H, H-50), 7.35 (d, J ¼ 5.8
Hz, 1H, thiophene, H-7), 7.23 (d, J ¼ 5.8 Hz, 1H, H-6), ms:
m/z (%) 302 (Mþ, 5), 152 (19), 126 (12), 97 (10), 84 (55), 66
(100), 55 (20). Anal. Calcd. for C13H7ClN4OS: C, 51.58; H,
2.33, N, 18.51. Found: C, 51.73; H, 2.41; N, 18.36.
1-m-Tolylthieno[2,3-e][1,2,4]triazolo[4,3-a]pyramidin-5(4H)-
one (5h). Yield 61%, mp > 400ꢁC; IR (KBr) 3430, 1666
1
cmꢀ1; H NMR (dimethyl sulfoxide-d6): d 13.10 (bs, 1H, NH),
1-(3-Bromophenyl)thieno[3,2-e][1,2,4]triazolo[4,3-a] pyra-
midin-5(4H)-one (6g). Yield 71%, mp > 400ꢁC; IR (KBr)
7.84 (d, J ¼ 5.8 Hz, 1H, thiophene, H-7), 7.47–7.40 (m, 4H,
phenyl, H-20, H-40 H-50 and H-60), 6.71 (d, J ¼ 5.8 Hz, 1H, H-
8), 2.39 (s, 1H, Me), ms: m/z (%) 282 (Mþ, 22), 152 (5), 149
(19), 84 (35), 66 (99), 52 (10). Anal. Calcd. for C14H10N4OS:
C, 59.56; H, 3.57, N, 19.85. Found: C, 59.67; H, 3.62; N,
19.69.
3430, 1660 cmꢀ1 1H NMR (dimethyl sulfoxide-d6): d 8.30
;
(bs, 1H, NH), 7.94 (s, 1H, phenyl, H-20), 7.81 (d, 1H, H-60),
7.73 (d, 1H, H-40), 7.54 (t, 1H, H-50), 7.36 (d, J ¼ 5.8 Hz, 1H,
thiophene, H-7), 7.26 (d, J ¼ 5.8 Hz, 1H, H-6) ms: m/z (%)
347 (Mþ, 7), 152 (11), 97 (10), 84 (55), 66 (100), 60 (22), 54
(23). Anal. Calcd. for C13H7BrN4OS: C, 44.97; H, 2.03, N,
16.14. Found: C, 45.17; H, 2.15; N, 16.32.
1-Phenylthieno[3,2-e][1,2,4]triazolo[4,3-a]pyrimidin-5(4H)-
one (6a). Yield 66%, mp > 400ꢁC; IR (KBr) 3430, 1662
1
cmꢀ1; H NMR (dimethyl sulfoxide-d6): d 8.82 (bs, 1H, NH),
1-m-Tolylthieno[3,2-e][1,2,4]triazolo[4,3-a]pyramidin-5(4H)-
one (6h). Yield 61%, mp > 400ꢁC; IR (KBr) 3430, 1662
7.68–7.66 (m, 2H, phenyl, H-20 and H-60), 7.58–7.55 (m, 3H,
H-30, H-40 and H-50), 7.39 (d, J ¼ 5.8 Hz, 1H, thiophene, H-
7), 7.21 (d, J ¼ 5.8 Hz, 1H, H-6), ms: m/z (%) 268 (Mþ,
100), 152 (21), 110 (10), 84 (48), 66 (100), 57(10). Anal.
Calcd. for C13H8N4OS: C, 55.20; H, 3.01, N, 20.88. Found: C,
55.09; H, 3.12; N, 20.92.
1
cmꢀ1; H NMR (dimethyl sulfoxide-d6): d 8.38 (bs, 1H, NH),
7.48–7.39 (m, 4H, phenyl, H-20, H-40 H-50 and H-60), 7.34 (d,
J ¼ 5.8 Hz, 1H, thiophene, H-7), 7.18 (d, J ¼ 5.8 Hz, 1H, H-
6), 2.41 (s, 1H, Me), ms: m/z (%) 282 (Mþ, 5), 152 (10), 84
(68), 66 (100), 60 (21), 54 (25). Anal. Calcd. for C14H10N4OS:
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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Synthesis of New 1-Phenylthieno[1,2,4]triazolo[4,3-a]pyrimidin-5(4H)-one Derivatives
603
C, 59.56; H, 3.57, N, 19.85. Found: C, 59.74; H, 3.49; N,
20.01.
Preparation of 5a by alternative synthesis (Scheme
3). The preparation of 5a from 7 was achieved through a serial
of reactions as shown Scheme 3.
1-Phenylthieno[2,3-e][1,2,4]triazolo[4,3-a]pyrimidin-5(4H)-
one (5a). Yield 82%, mp 265–267ꢁC; IR (KBr) 3430, 1662
1
cmꢀ1; H NMR (dimethyl sulfoxide-d6): d 11.66 (bs, 1H, NH),
7.94 (d, J ¼ 5.8 Hz, 1H, thiophene, H-7), 7.71–7.62 (m, 2H,
phenyl, H-20 and H-60), 7.60–7.57 (m, 3H, H-30, H-40 and H-
50), 6.63 (d, J ¼ 5.8 Hz, 1H, H-8), ms: m/z (%) 268 (Mþ,
100), 152 (52), 110 (40), 96 (10), 84 (41), 77 (30), 66 (26),
57(54). Anal. Calcd. for C13H8N4OS: C, 55.20; H, 3.01, N,
20.88. Found: C, 55.09; H, 3.12; N, 20.79.
Methyl-3(3-benzylthioureido)thiophene-2-carboxylate (9A). Yield
1
59%, mp 132–133ꢁC; H NMR (dimethyl sulfoxide-d6): d 10.08
(s, 1H, NH), d 9.59 (s, 1H, NH), 8.36 (d, J ¼ 5.8 Hz, 1H, thio-
phene, H-5), 7.80 (d, J ¼ 5.8 Hz, 1H, H-4), 7.37–7.27 (m, 5H,
phenyl), 4.75 (d, 2H, benzyl), 3.82 (s, 3H, Me), ms: m/z 306
(Mþ), Anal. Calcd. for C14H14N2O2S2: C, 54.88; H, 4.61, N, 9.14.
Found: C, 54.69; H, 4.44; N, 9.32.
3-Benzyl-2-thioxo-2,3-dihydrothieno[2,3-d]pyrimidin-4(1H)-
one (11A). Yield 50%, mp 240–242ꢁC; 1H NMR (dimethyl
sulfoxide-d6): d 13.56 (s, 1H, NH), 8.20 (d, J ¼ 5.8 Hz, 1H,
thiophene, H-6), 7.05 (d, J ¼ 5.8 Hz, 1H, H-7), 7.30–7.22 (m,
5H, phenyl), 5.63 (s, 2H, benzyl), ms: m/z 274 (Mþ), Anal.
Calcd. for C13H10N2OS2: C, 56.91; H, 3.67, N, 10.21. Found:
C, 56.75; H, 3.77; N, 10.09.
REFERENCES AND NOTES
[1] El-Hawash, S. A.; Habib, N. S.; Fanaki, N. H. Pharmazie
1999, 54, 808.
[2] Dickinson, R. P., Bell, A. W.; Hitchcock, C. A.; Narayama-
Swami, S.; Ray, S. J.; Richardson, K.; Troke, P. F. Bioorg Med Chem
Lett 1996, 6, 2031.
[3] Palaska, E.; Sahin, G.; Kelicen, P.; Durlu, N. T.; Altinok,
G. Farmaco 2002, 57, 101.
3-Benzyl-2-(methylthio)thieno[3,2-d]pyrimidin-4(3H)-one
1
(13A). Yield 73%, mp 171–173ꢁC; H NMR (dimethyl sulfox-
[4] El-Sherberry, M. A.; El-Ashmawy, M. B.; El-Subbagh, H. I.;
El-Emam, A. A.; Badria, F. A. Eur J Med Chem 1995, 30, 445.
[5] Nagamatsu, T.; Ahmed, S.; Hossion, A. M. L.; Ohno, S.
Heterocycles 2007, 73, 777.
ide-d6): d 8.18 (d, J ¼ 5.8 Hz, 1H, thiophene, H-6), 7.34 (d, J
¼ 5.8 Hz, 1H, H-7), 7.31–7.19 (m, 5H, phenyl), 5.32 (s, 2H,
benzyl), 2.56 (s, 3H, Me), ms: m/z 288 (Mþ), Anal. Calcd. for
C14H12N2OS2: C, 58.31; H, 4.19, N, 9.71. Found: C, 58.47; H,
4.32; N, 9.50.
[6] (a) Shawali, A. S.; Hassaneen, H. M.; Shurrab, N. Kh. Tet-
rahedron 2008, 64, 10339; (b) Baraldi, P. G.; El-Kasher, H.; Farghaly,
A.-R.; Venelle, P.; Fruttarolo, F. Tetrahedron 2004, 60, 5093.
[7] Pandey, S. K.; Singh, A.; Singh, A.; Nizamuddin Eur J
Med Chem 2009, 44, 1188.
3-Benzyl-2-hydrazinylthieno[3,2-d]pyrimidin-4(3H)-one
1
(15A). Yield 59%, mp 194–196ꢁC; H NMR (dimethyl sulfox-
ide-d6): d 10.19 (s, 1H, NH), 8.02 (d, J ¼ 5.8 Hz, 1H, thio-
phene, H-6), 7.10 (d, J ¼ 5.8 Hz, 1H, H-7), 7.30–7.15 (m, 5H,
phenyl), 5.25 (s, 2H, benzyl), 4.29 (bs, 2H,NH2), ms: m/z 272
(Mþ), Anal. Calcd. for C13H12N4OS: C, 57.34; H, 4.44, N,
20.57. Found: C, 57.13; H, 4.30; N, 20.40.
[8] (a) Alagarsamy, V.; Solomon, V. R.; Parthiban, P.; Muruge-
san, S.; Saravanan, G.; Anjana, G. V. J Heterocycl Chem 2008, 45,
709; (b) Alagarsamy, V.; Solomon, V. R.; Murugan, M. Bioorg Med
Chem 2007, 15, 4009.
[9] (a) Hamed, A. A.; Zeid, I. F.; El-Ganzory, H. H.; Abdel-
Aal, M. T. Manatsh Chem 2008, 139, 809; (b) El-Gazzar, A. B. A.;
Hassan, N. A. Molecules, 2000, 5, 835.
3-Benzyl-(E)-2-(2-benzylidenehydrazinyl)thieno[3,2-d]pyri-
1
midin-4(3H)-one (17A). Yield 77%, mp 185–187ꢁC; H NMR
(dimethyl sulfoxide-d6): d 9.52 (s, 1H, NH), 8.45 (s, 1H, imine
proton), 7.77 (d, 2H, N¼¼CAPh, H-20 and H-60), 7.65 (d, J ¼
5.8 Hz, 1H, thiophene, H-6), 7.60 (d, 2H, CH2-Ph, H-200, and
H-600), 7.40 (m, 3H, N¼¼CAPh, H-30, H-40 and H-50), 7.33–
7.22 (m, 3H, CH2-Ph, H-300, H-400, and H-500), 6.87 (d, J ¼ 5.8
Hz, 1H, H-7), 5.36 (s, 2H, benzyl), ms: m/z 360 (Mþ), Anal.
Calcd. for C20H16N4OS: C, 66.65; H, 4.47, N, 15.54. Found:
C, 66.54; H, 4.29; N, 15.40.
4-Benzyl-1-phenylthieno[2,3-e][1,2,4]triazolo[4,3-a]pyrimi-
din-5(4H)-one (19A). Yield 79%, mp 224–226ꢁC; 1H NMR
(dimethyl sulfoxide-d6): d 8.09 (d, J ¼ 5.8 Hz, 1H, thiophene,
H-7), 7.77–7.75 (m, 2H, N¼¼CAPh, H-20 and H-60), 7.67–7.45
(m, 8H, N¼¼CAPh, H-30, H-40, H-50 and CH2-Ph, H-200, H-300,
H-400, H-500, H-600), 6.74 (d, J ¼ 5.8 Hz, 1H, H-8), 5.59 (s, 2H,
benzyl), ms: m/z 358 (Mþ), Anal. Calcd. for C20H14N4OS: C,
67.02; H, 3.94, N, 15.63. Found: C, 66.88; H, 3.81; N, 15.82.
[10] Jo, B. S.; Son, H. Y.; Song, Y.-H. Heterocycles 2008, 75,
3091.
[11] (a) Song, Y.-H.; Son, H. Y. J Heterocycl Chem, to appear;
(b) Lee, H. M.; Song, Y.-H. Bull Korean Chem Soc 2010, 31, 185;
(c) Jo, B. S.; Song, Y.-H. Syn Commun 2009, 39, 4407; (d) Song,
Y.-H.; Jo, B. S. J Heterocycl Chem 2009, 46, 1132; (e) Song, Y.-H.;
Jo, B. S.; Lee, H. M. Heterocycl Commun 2009, 15, 203; (f) Song,
Y.-H.; Jo, B. S. Bull Korean Chem Soc 2009, 30, 969; (g) Lee, H. M.;
Song, Y.-H. J Kor Chem Soc 2009, 53, 387; (h) Kim, K. H.; Song,
Y.-H. Heterocycl Commun 2008, 14, 405; (i) Song, Y.-H.; Seo, J. J
Heterocycl Chem 2007, 44, 1439; (j) Song, Y.-H. Heterocycl Commun
2007, 13, 33.
[12] Modica, M.; Santagati, M.; Russo, F.; Parotti, L.; Gioia, L.
D.; Selvaggini, C.; Salmona, M.; Mennini, T. J Med Chem 1997, 40,
574.
[13] Shawali, A. S.; Gomha, S. M. Tetrahedron 2002, 58, 8559.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet