1,3,4-thia- and -selenadiazole and 1,2,4-triazolo[4,3-a]pyrimidine derivatives from hydrazonoyl halides

Article abstract of DOI:10.1002/hc.10156

A study was performed on 1,3,4-thia- and -Selenadiazole and 1,2,4-triazolo[4,3-a]pyrimidine derivatives from hydrazonoyl halides. The reactivity of hydrazonoyl halides toward some alkyl carbodithiates, potassium thiocyanate, potassium selenocyanate and py

Full text of DOI:10.1002/hc.10156

Heteroatom Chemistry
Volume 14, Number 5, 2003
1,3,4-Thia- and -Selenadiazole and
1,2,4-Triazolo[4,3-a]pyrimidine Derivatives
from Hydrazonoyl Halides
Nadia A. Abdel-Riheem, Nora M. Rateb, Ali A. Al-Atoom,
and Abdou O. Abdelhamid
Department of Chemistry, Faculty of Science, Cairo University, Giza 12316, Egypt
Received 14 October 2002; revised 3 January 2003
RESULTS AND DISCUSSION
ABSTRACT: 1,2,4-Triazolo[4,3-a]pyrimidines, thia-
diazolines, selenadiazolines, and unsymmetrical
azines were synthesized via reactions of a 4-isopro-
pylbenzoyl bromide 4-nitrophenylhydrazone with
each of potassium thiocyanate, potassium seleno-
cyanate, ethyl 6-methyl-4-[4-(methylethyl)phenyl]-2-
methylthio-3,4-dihydropyrimidine-5-carboxylate, and
Treatment of 4-isopropylbenzoyl bromide 4-nitro-
phenylhydrazone (1) [11] with methyl carbod-
ithioate 2aA [12] in ethanolic triethylamine at room
temperature gave benzaldehyde 3-(4-nitrophenyl)-5-
(4-isopropylphenyl)-1,3,4-thiadiazol-2(3H)-ylidene-
hydrazone (4a) (Scheme 1).
The structure of 4a was confirmed by elemen-
tal analysis, spectral data, and alternative synthesis.
1H NMR of 4a showed signals at δ = 1.26 (d, 6H,
(CH3)2CH ), 2.95 (sept, 1H, (CH3)2CH ), and 6.97–
8.53 (m, 14H, ArH and CH (vinyl)). Also, treatment
of 1 with each of 2aB [13] and 2aC [13] in ethanolic
triethylamine gave a product identical in all respects
(mp, mixed mp, and spectra) with 4a.
ꢀ
C
alkyl carbodithioate.
2003 Wiley Periodicals, Inc.
Heteroatom Chem 14:421–426, 2003; Published online
in Wiley InterScience (www.interscience.wiley.com). DOI
10.1002/hc.10156
INTRODUCTION
Similarly, compound 1 reacted with other alkyl
carbodithioates 2b–q(A–C) [12,13] to give the 1,3,4-
thiadiazole derivatives 4b–q, respectively. Products
4a–q are assumed to be formed via elimination
of alkanethiol (R1SH) from the corresponding cy-
cloadduct 3, which formed from 1,3-dipolar cycload-
dition (or 1,3-addition) of nitrile imide (generated in
situ from 1 and triethylamine) to C S 2 (Scheme 1).
Moreover, treatment of 1 with each of potassium
thiocyanate and potassium selenocyanate gave
5-[4-(methylethyl)phenyl]-3-(4-nitrophenyl)-1,3,4-
thiadiazol-2(3H)imine (6a) and 5-[4-methylethyl)-
phenyl]-3-(4-nitrophenyl)-1,3,4-selenadiazol-2(3H)-
imine (6b), respectively. The structures of 6a and
6b were elucidated on the basis of elemental anal-
yses, spectral data, an alternative synthesis, and
Hydrazonoyl halides have been widely employed
for the synthesis of heterocyclic compounds [2–4].
1,3,4-Thiadiazole derivatives have become useful in
medicine, agriculture, and in many fields of technol-
ogy [5]. As an extension of our study [6–10] and of
our syntheses of 1,3,4-thiadiazoles, we report here
the reactivity of hydrazonoyl halides toward some
alkyl carbodithioates, potassium thiocyanate, potas-
sium selenocyanate, and pyrimidine thione.
Reactions of Hydrazonoyl Halides, Part 36 [1].
Correspondence to: Abdou O. Abdelhamid; e-mail: abdou@
main-scc.cairo.eun.eg.
c
ꢀ
2003 Wiley Periodicals, Inc.
421

422 Abdel-Riheem et al.
SCHEME 2
SCHEME 1
by thermolysis of 9a and 9b in boiling xylene. IR
spectra of 10a,b revealed a band near ν = 1685 cm−1
(CO).
its nitrosation and acylation reactions. The 1H
NMR spectrum of 6a showed signals at δ = 1.29
(d, 6H, (CH3)2CH ), 2.97 (sept, 1H, (CH3)2CH ),
and 7.25–8.42 (m, 9H, ArH and NH). The IR of 6a
and 6b each revealed a band at ν = 3380 cm−1 (NH)
and no absorption bands in ν = 2000–2200 cm−1
due to free SCN or SeCN. Also, treatment of 1 with
thiourea in boiling ethanol gave a product identical
in all respects (mp, mixed mp, and spectra) with 6a.
These results indicate that hydrazone 5, amidiazone
7, or 2,2-diaminothiadiazoline 8 are not the final
products, and that 5 and 8 readily gave 6a either
by cyclization or by elimination of one molecule of
ammonia (Scheme 2).
Acylation of each 6a and 6b with acetic an-
hydride or with benzoyl chloride in pyridine af-
forded 5-[4-(methylethyl)phenyl]-3-(4-nitrophenyl)-
(1,3,4-thia/selenadiazolin-2-ylidene)amide (11a,b),
and benzamide (12a,b), respectively. Spectral data
and elemental analyses confirmed their structures.
1H NMR spectrum of 11a showed signals at δ = 1.30
(d, 6H, (CH3)2CH ), 2.40 (s, 3H, CH3CON ), 3.00
(sept, 1H, (CH3)2CH ), and 7.25–8.48 (m, 8H, ArH).
Its IR revealed a band at ν = 1640 cm−1 (CH3CON ).
Nitrosation of each 6a and 6b with saturated
sodium nitrite in acetic acid at 0–5◦C gave N-nitroso-
5-[4-(methylethyl)phenyl]-3-(4-nitrophenyl)-1,3,4-
thia/selenadiazol-2(3H)imine (9a,b), respectively.
5-[4-(Methylethyl)phenyl]-3-(4-nitrophenyl)-1,3,
4-thia/selenadiazolin-2-one (10a,b) were prepared
Next, treatment of ethyl 4-methyl-6-[4-(methy-
lethyl)phenyl]-2-thioxo-1,3,6-trihydropyrimidine-5-
carboxylate (13) with the hydrazonoyl halides 14a–g
in chloroform and triethylamine gave the 1,2,4-
triazolo[4,3-a]pyrimidine-5-carboxylates 18a–g, re-
spectively. The structure of 18 was elucidated on the
base of elemental analysis, spectra, and alternative
synthesis. 1H NMR spectrum of 18a showed signals
at δ = 1.18 (d, 6H, (CH3)2CH)), 1.25 (t, 3H, CH2CH3),
2.52 (s, 3H, CH3), 2.83 (sept, 1H, (CH3)2CH )), 3.94
(s,3H,OCH3), 4.12 (q, 2H, CH2CH3), 6.83 (s, 1H, CH),
and 7.07–8.21 (m, 9H, ArH). Its IR spectrum re-
vealed bands at ν = 1735 and 1689 cm−1 (CO). Ethyl
6-methyl-4-[4-(methylethyl)phenyl]-2-methylthio-
3,4-dihydropyrimidine-5-carboxylate (19) reacted
with the appropriate hydrazonoyl halides 14a–g
in boiling ethanolic sodium ethoxide solution gave
products identical in all respects (mp, mixed mp,
and spectra) with the corresponding 18a–g.
The formation of 18 can be explained via
1,3-dipolar cycloaddition or 1,3-addition of nitrile
imides 15 (prepared in situ from hydrazonoyl halides
14 with triethylamine or sodium ethoxide) to C S of
13 (or C N of 19) to give intermediate 16 (or 20),
with ring opening and ring closure to afford the final
products 18 by elimination of hydrogen sulfide (or
methyl mercaptan from 20) (Scheme 3).
Treatment of 1 with methyl benzoylhydrazine-
carbodithioate (21a) in ethanolic triethylamine gave

1,3,4-Thia- and -Selenadiazole and 1,2,4-Triazolo[4,3-a]pyrimidine Derivatives 423
SCHEME 5
hydrogen peroxide in acetic acid to give a product
identical in all respects (mp, mixed mp, and spectra)
with compound 25.
EXPERIMENTAL
All melting points were determined on an elec-
trothermal apparatus and are uncorrected. IR spec-
tra were recorded (KBr discs) on a Shimadzu FT-IR
SCHEME 3
1
8201 PC spectrophotometer. H NMR spectra were
recorded in CDCl3 and (CD3)2SO solutions on a Var-
2,3-dihydro-1,3,4-thiadiazole 23 (Scheme 4). Its
structure was elucidated on the basis of elemental
analysis, spectral data, and alternative synthesis. 1H
NMR spectrum showed signals at δ = 1.20 (d, 6H,
(CH3)2CH ), 2.96 (sept, 1H, (CH3)2CH ), 7.20–8.35
(m, 13H, ArH), and 8.42 (s, br, 1H, NH). Treatment
of 1 with each of 21b and 21c gave products identi-
cal in all respects (mp, mixed mp, and spectra) with
23.
ian Gemini 300 MHz spectrometer and chemical
shifts were expressed in δ units using TMS as internal
reference. Elemental analyses were carried out at the
Microanalytical Center of the Cairo University. Hy-
drazonoyl halides [14–21] and alkyl carbodithioates
[12,13] were prepared as previously reported.
Synthesis of Thiadiazolines 4a–q and 23
Finally, treatment of 1 with each of sodium ben-
zenethiolate and sodium benzenesulfinate in ethanol
afforded the hydrazones 24 and 25, respectively
(Scheme 5). Compound 24 was easily oxidized by
Triethylamine (0.75 ml, 0.005 mol) was added drop-
wise with stirring to a mixture of the appro-
priate alkyl carbodithioates 2a–q(A–C) or 21a–c
(0.005 mol) and compound 1 (1.8 g, 0.005 mol) in
ethanol (20 ml). The resulting solid, which formed af-
ter 30 min, was collected and crystallized from acetic
acid and gave the corresponding thiadiazolines 4a–q
and 23, respectively, in a good yield (Tables 1 and 2).
Synthesis of 1,3,4-Thiadiazoline 6a
and 1,3,4-Selenadiazoline 6b
Method A. A mixture of 1 (1.8 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 3 h. The
resulting solid was collected, washed with water, and
crystallized from ethanol to give 6a and 6b, respec-
tively (Tables 1 and 2).
SCHEME 4

424 Abdel-Riheem et al.
TABLE 1 Characterization Data of the Newly Synthesized Compounds
Analyses: Calcd, Found
m.p. (◦C)
Yield (%)
Mol. Formula (Mol. Wt)
C
H
N
S
4a 200–202 (yellow)
4b 178–180 (yellow)
4c 157–158 (yellow)
4d 162–164 (yellow)
4e 164–165 (yellow)
4f 238–240 (yellow)
4g 205–207 (yellow)
4h 153–155 (yellow)
89
85
80
82
84
75
78
88
89
90
86
78
88
89
69
75
74
73
78
72
70
78
77
76
79
82
77
68
75
77
76
79
72
70
77
85
85
88
77
C24H21N5O S (443.53)
64.99, 65.10 4.77, 4.90 15.79, 15.60 7.23, 7.40
65.63, 65.80 5.07, 4.99 15.31, 15.30 7.00, 7.20
63.41, 63.50 4.49, 4.60 14.79, 14.80 6.77, 6.50
58.78, 58.60 4.26, 4.40 15.58, 15.80 14.26, 14.20
60.10, 60.20 4.42, 4.30 16.16, 16.20 7.39, 7.10
62.12, 62.00 4.54, 4.60 18.91, 19.10 7.21, 7.30
66.51, 66.40 4.94, 5.10 14.92, 15.00 6.82, 6.70
66.78, 66.80 5.60, 5.50 14.42, 14.30 6.60, 6.70
61.59, 61.60 4.34, 4.50 14.37, 14.40 6.57, 6.30
65.63, 65.40 5.07, 4.80 15.31, 15.10 7.00, 7.20
61.73, 61.70 4.73, 4.80 15.65, 15.50 7.16, 7.10
59.60, 59.50 4.57, 4.70 15.12, 15.10 13.83, 14.00
62.87, 62.70 4.84, 4.50 18.33, 18.20 6.99, 7.10
63.72, 63.70 5.35, 5.50 16.15, 16.00 7.39, 7.50
64.41, 64.20 5.63, 5.30 15.65, 15.50 7.16, 6.90
65.06, 65.10 5.90, 6.00 15.17, 15.00 6.94, 6.80
67.86, 67.60 5.08, 4.90 14.13, 14.00 6.47, 6.50
59.99, 60.10 4.74, 4.70 16.46, 16.60 9.41, 9.30
52.72, 52.80 4.16, 4.00 14.47, 14.60
55.28, 55.30 4.09, 4.10 18.96, 19.00 8.68, 8.80
49.05, 48.90 3.63, 3.70 16.82, 16.90
59.81, 59.60 4.42, 4.40 12.31, 12.10 9.39, 9.40
52.58, 52.60 3.89, 3.90 10.82, 10.90
59.67, 60.00 4.74, 4.80 14.65, 14.60 8.38, 8.40
53.15, 53.20 4.23, 4.30 13.05, 13.10
64.85, 65.00 4.54, 4.60 12.60, 12.70 7.21, 7.10
58.66, 58.70 4.00, 3.90 11.40, 11.30
C25 23
H
N5O2S (457.54)
C
25H23N5O2S (473.54)
C22 19
H
N5O3S (449.52)
C22 19
H
N5O2S2(433.48)
C
23H20N6O32S (444.50)
C26H23N5O S (469.55)
C
C
C
C
C
C
27H27N5O2S (485.59)
4i
4j
226–228 (yellow)
166–168 (yellow)
25H21N5O2S (487.52)
25H23N5O4S (457.54)
23H21N5O2S (447.50)
23H21N5O3S (463.55)
24H22N6O22S2(458.53)
4k 221–223 (yellow)
4l 213–215 (yellow)
4m 188–191 (yellow)
4n 220–222 (yellow)
4o 170–172 (yellow)
4p 150–152 (yellow)
4q 250–252 (yellow)
6a 168–170 (yellow)
6b 114–115 (yellow)
9a 145 (pale yellow)
9b 150 (pale yellow)
10a 154–155 (red)
C23 23
C24 25
H
N5O S (433.52)
N5O2S (447.55)
H
C
C
C
C
C
C
C
C
C
C
C
25H27N5O2S (461.57)
28H25N5O2S (495.59)
17H16N4O22S (340.39)
17H16N4O2Se (387.30)
17H15N5O S (369.39)
17H15N5O3Se (416.29)
17H15N3O33S (341.37)
17H15N3O3Se (388.29)
19H18N4O3S (382.43)
19H18N4O3Se (429.34)
24H20N4O3S (444.50)
10b 155–157 (red)
11a 186–188 (pale yellow)
11b 210–212 (pale yellow)
12a 172–173 (pale yellow)
12b 165–167 (pale yellow)
C24 20
H
N4O3Se (491.41)
13
178–180 (yellow)
C
C
C
C
C
C
C
C
C
17H22N2O2S (318.42)
64.13, 64.10 6.96, 7.00 8.80, 8.60
67.81, 67.70 6.09, 6.10 12.17, 12.00
68.33, 68.10 6.37, 6.30 11.81, 11.70
71.38, 71.10 5.99, 6.10 13.43, 13.20
70.25, 70.30 6.35, 6.40 12.60, 12.50
73.50, 73.40 6.00, 6.20 11.06, 10.90
10.06, 9.20
18a 119–120 (yellow)
18b 109–110 (yellow)
18c 149–151 (yellow)
18d 128–129 (yellow)
18e 120–122 (orange)
18f 187–188 (orange)
18g 113–115 (brown)
26H28N4O4 (460.54)
27H30N4O4 (474.57)
31H31N5O (521.63)
26H28N4O33 (444.54)
31H30N4O3 (506.61)
29H28N4O3S (512.62)
35H32N4O3 (556.65)
18H24N2O2S (332.45)
67.95, 67.10 5.51, 5.30 10.93, 10.70 6.26, 6.40
75.52, 75.30 5.80, 5.60 10.07, 9.80
19
23
24
25
69–70 (colorless)
190–192 (yellow)
220–222 (yellow)
120 (yellow)
65.03, 65.10 7.28, 7.40 8.43, 8.30
9.64, 9.50
C24 21
C
C
H
N5O S (459.51)
62.73, 62.90 4.61, 4.50 15.24, 15.30 6.97, 7.10
67.50, 67.30 5.41, 5.60 10.73, 10.80 8.19, 8.30
22H21N3O32S (391.48)
22H21N3O4S (423.48)
62.40, 62.20 5.00, 5.10 9.92, 10.00
7.57, 7.80
Method B. A mixture of 1 (1.8 g, 0.005 mol) and
Thermolysis of 9a and 9b
thiourea (0.38 g, 0.005 mol) in ethanol (25 ml) was re-
fluxed for 30 min. The solid product that formed after
cooling was collected and crystallized from ethanol.
It was identical in all respects (mp, mixed mp, and
spectra) with 6a.
A solution of 9a, 9b (0.5 g) in xylene (20 ml) was re-
fluxed for 15 min. Then the solvent was evaporated
under reduced pressure. The residue oil was tritu-
rated with petroleum ether (40–60◦C) and the solid
formed was collected and crystallized from acetic
acid to give 1,3,4-thiadiazolinone 10a and 1,3,4-
selenadiazolinone 10b, respectively (Tables 1 and 2).
Nitrosation of 6a and 6b
A cold saturated solution of sodium nitrite (10 ml)
was added dropwise to a solution of 6a or 6b (1 g)
in acetic acid (20 ml) in an ice bath while stirring.
The reaction mixture was stirred for 30 min. The re-
sulting solid was collected, washed with water, and
crystallized from acetone to give 9a and 9b, respec-
tively (Tables 1 and 2).
Acylation of 6a and 6b
Acetylation. A mixture of 6a or 6b (1 g) in acetic
acid (10 ml) and acetic anhydride (5 ml) was warmed
for 5 min at 70◦C. The reaction mixture was poured
onto ice water (40 ml). The solid was collected and

1,3,4-Thia- and -Selenadiazole and 1,2,4-Triazolo[4,3-a]pyrimidine Derivatives 425
TABLE 2 1H NMR Spectroscopic Data of Some Synthesized Compounds
4b
4c
1.26 (d, 6H, (CH3)2CH), 2.37 (s, 3H, 4-CH3C6H4), 2.97 (sept, 1H, (CH3)2CH), 6.97–8.50 (m, 13H, ArH and CH N).
1.26 (d, 6H, (CH3)2CH), 2.98 (sept, 1H, (CH3)2CH), 3.84 (s, 3H, 4-CH3OC6H4), 6.97–8.53 (m, 13H, ArH and CH N).
1.28 (d, 6H, (CH3)2CH), 2.98 (sept, 1H, (CH3)2CH), 7.07–8.61 (m, 12H, ArH and CH N).
1.28 (d, 6H, (CH3)2CH), 2.98 (sept, 1H, (CH3)2CH), 6.53–8.52 (m, 12H, ArH’s and CH N).
1.28 (d, 6H, (CH3)2CH), 2.98 (sept 1H, (CH3)2CH), 7.25–8.68 (m, 13H, ArH and CH N).
1.15 (d, 6H, (CH3)2CH), 2.40 (s, 3H, CH3), 2.85 (sept, 1H, (CH3)2CH), 7.12–8.41 (m, 13H, ArH).
1.18 (d, 6H, (CH3)2CH), 2.40 (s, 3H, CH3), 2.86 (sept, 1H, (CH3)2CH), 6.95–8.41 (m, 11H, ArH).
1.16 (d, 6H, (CH3)2CH), 2.32 (s, 3H, CH3), 2.90 (sept, 1H, (CH3)2CH), 6.39–8.42 (m, 11H, ArH’s).
1.28 (d, 6H, (CH3)2CH), 2.50 (s, 3H, CH3), 2.97 (sept, 1H, (CH3)2CH), 7.26–8.51 (m, 12H, ArH).
1.28 (d, 6H, (CH3)2CH), 2.96 (sept, 1H, (CH3)2CH), 7.25–8.34 (m, 9H, ArH and NH).
1.28 (d, 6H, (CH3)2CH), 2.95 (sept, 1H, (CH3)2CH), 7.25–8.21 (m, 8H, ArH).
1.27 (d, 6H, (CH3)2CH), 2.92 (sept, 1H, (CH3)2CH), 7.25–8.25 (m, 8H, ArH).
1.28 (d, 6H, (CH3)2CH), 2.92 (sept,1H, (CH3)2CH), 7.20–8.15 (m, 8H, ArH).
1.28 (d, 6H, (CH3)2CH), 2.90 (sept, 1H, (CH3)2CH), 7.20–8.24 (m, 8H, ArH).
1.28 (d, 6H, (CH3)2CH), 2.40 (s, 3H, CH3CON ), 2.98 (sept, 1H, (CH3)2CH), 7.25–8.48 (m, 8H, ArH).
1.29 (d, 6H, (CH3)2CH), 2.92 (sept, 1H, (CH3)2CH), 7.35–8.52 (m, 13H, ArH).
4d
4e
4f
4j
4k
4l
4m
6b
9a
9b
10a
10b
11b
12a
12b
13
1.20 (d, 6H, (CH3)2CH), 2.90 (sept, 1H, (CH3)2CH), 7.16–8.40 (m, 13H, ArH).
1.15 (t, 3H, CH2CH3), 1.26 (d, 6H, (CH3)2CH), 2.53 (s, 3H, CH3), 2.82 (sept, 1H, (CH3)2CH), 4.08 (q, 2H, CH2CH3),
6.76 (s, 1H, CH), 7.21–8.35 (m, 4H, ArH), 9.61 (s, 1H, NH), 10.53 (s, 1H, NH).
18b
18c
18d
18e
18f
1.19 (t, 3H, CH3CH2), 1.25 (d, 6H, (CH3)2CH), 1.34 (t, 3H, CH3CH2), 2.51 (s, 3H, CH3), 2.82 (sept, 1H, (CH3)2CH),
4.11 (q, 2H, CH2CH3), 4.42 (q, 2H, CH2CH3), 6.83 (s, 1H, CH), 7.06–8.21 (m, 9H, ArH).
1.15 (t, 3H, CH3CH2), 1.22 (d, 6H, (CH3)2CH), 2.54 (s, 3H, CH3), 2.83 (sept, 1H, (CH3)2CH), 4.07 (q, 2H, CH2CH3),
7.03–8.20 (m, 15H, ArH and CH), 8.37 (s, br, 1H, NH).
1.13 (t, 3H, CH3CH2), 1.21 (d, 6H, (CH3)2CH), 2.51 (s, 3H, CH3), 2.53 (s, 3H, CH3), 2.81 (sept, 1H, (CH3)2CH), 4.08
(q, 2H, CH2CH3), 6.85 (s, 1H, CH), 7.05–8.23 (m, 9H, ArH).
1.12 (t, 3H, CH3CH2), 1.23 (d, 6H, (CH3)2CH), 2.56 (s, 3H, CH3), 2.75 (sept, 1H, (CH3)2CH), 4.13 (q, 2H, CH2CH3),
6.96 (s, 1H, CH), 7.01–8.24 (m, 14H, ArH).
1.12 (d, 6H, (CH3)2CH), 1.24 (t, 3H, CH3CH2), 2.55 (s, 3H, CH3), 2.80 (sept, 1H, (CH3)2CH), 4.08 (q, 2H, CH2CH3),
7.00–8.29 (m, 13H, ArH and CH).
crystallized to give the N-acetyl derivatives 11a and
11b, respectively (Tables 1 and 2).
Synthesis of Ethyl 6-Methyl-4-[4-(methylethyl)-
phenyl]-2-methylthio-3,4-dihydropyrimidine-5-
carboxylate (19)
Iodomethane (0.006 mol) was added portionwise
with stirring to a warm ethanolic sodium ethox-
ide solution [prepared by dissolving sodium metal
(0.005 mol) in ethanol 15 ml] and compound 13
(0.005 mol). The reaction mixture was left overnight
at room temperature; the solid precipitate was col-
lected and crystallized from ethanol to give 19
(Table 1).
Benzoylation. 6a or 6b (0.5 g) and benzoyl chlo-
ride (3 ml) in pyridine (15 ml) were refluxed for 10
min, poured onto ice water (50 ml) and acidified with
hydrochloric acid. The resulting product was col-
lected and washed several times with boiling water.
The solid was crystallized from acetic acid or N,N-
dimethylformamide to give the N-benzoyl deriva-
tives 12a and 12b, respectively (Tables 1 and 2).
Synthesis of 1,2,4-Triazolo[4,3-a]pyrimidines
18a–g
Synthesis of Ethyl 4-Methyl-6-[4-(methylethyl)-
phenyl]-2-thioxo-1,3,6-trihydropyrimidine-5-
carboxylate (13)
Method A. A mixture of the appropriate hydra-
zonoyl halides 14a–g (0.005 mol) and compound 13
(1.9 g, 0.005 mol) in chloroform containing triethy-
lamine (0.75 ml, 0.005 mol) was refluxed for 10 h.
Chloroform was evaporated under reduced pressure
and the residue solid was crystallized from ethanol
to give 18a–g, respectively (Tables 1 and 2).
A mixture of ethyl acetoacetate (0.1 mol, 13 g),
thiourea (0.012 mol, 8.2 g), and 4-(methylethyl)-
benzaldehyde (14.9 g, 0.1 mol) in ethanol (30 ml)
containing a catalytic amount of concentrated hy-
drochloric acid (10 drops) was refluxed for 3 h. The
reaction mixture was then allowed to stand at room
temperature overnight. The solid precipitate formed
was collected by filtration, washed with ethanol, and
crystallized from ethanol to give 13 (Tables 1 and 2).
Method B. Equimolar amounts of the hydra-
zonoyl halides 14a–g, 19, and sodium ethoxide

426 Abdel-Riheem et al.
[3] Huisgen, R.; Sustmann, R.; Wallbillich, G. Chem Ber
1976, 100, 1786.
[4] Abdelhamid, A. O.; Attaby, F. A. J Heterocycl Chem
1991, 28, 41.
[5] Kornis, D. I. In Comprehensive Heterocyclic Chem-
istry; Katritzky, A. R.; Rees, C. W.; Scriven, E. F. V.
(Eds.); Pergamon: Oxford, 1996; Vol. 4.
[6] Abdelhamid, A. O.; Sallam, M. M. M.; Amer, S. A. Het-
eroat Chem 2001, 12, 468.
(0.005 mol each) in ethanol (20 ml) were refluxed for
3 h. The reaction mixture was cooled and the result-
ing solid was collected and crystallized from ethanol
to give products identical in all respects (mp, mixed
mp, and spectra) with corresponding products ob-
tained by method A.
Synthesis of Hydrazones 24 and 25
[7] Abdelhamid, A. O.; Zohdi, H. F.; Ali, N. A. Molecules
2001, 5, 961.
A mixture of equimolar amounts of hydrazonoyl bro-
mide 1 and the appropriate sodium benzenethio-
late or sodium benzene sulfinate (0.005 mol each)
in ethanol (20 ml) was stirred for 4 h and left at
room temperature overnight. The resulting solid was
collected, washed with water, and crystallized from
ethanol to give hydrazones 24 and 25, respectively
(Table 1).
Alternative synthesis of 25 hydrogen peroxide
(5 ml, 30%) was added with stirring to a solution
of hydrazone 24 (0.5 g) in acetic acid (20 ml). The
reaction mixture was left at room temperature for
48 h and poured onto ice-cold water (50 ml). The
resulting solid was collected and crystallized from
ethanol to give a product identical in all respects (mp,
mixed mp, and spectra) with 25.
[8] Abdelhamid, A. O.; Rateb, N. M.; Dawood, K. M. Phos-
phorus Sulfur 2000, 167, 251.
[9] Zohdi, H. F.; Rateb, M. M.; Sallam, M. M. M.;
Abdelhamid, A. O. J Chem Res (S) 1998, 742; J Chem
Res (M) 3329.
[10] Abdelhamid, A. O.; Abdelgawad, S. M.; El-Sharnoby,
S. F. Phosphorus Sulfur Silicon Relat Elem 2002, 177,
2699.
[11] Scott, F. L.; Aylward, J. B. Tetrahedron Lett 1965, 841.
[12] Korosi, J. Ger Offen 1,934,899,29 Jan. 1970; Chem
Abstr 1970, 72, 100334s.
[13] Klayman, D. L.; Bartosevich, J. F.; Griffin, T. S.;
Mason, C. J.; Scovill, J. P. J Med Chem 1979, 22, 855.
[14] Fravel, G. Bull Soc Chim Fr 1904, 31, 150.
[15] Eweiss, N. F.; Osman, A. Tetrahedron Lett 1979, 1169.
[16] Wolkoff, P. Can J Chem 1975, 53, 1333.
[17] Shawali, A. S.; Osman, A. Tetrahedron 1971, 27,
2571.
[18] Shawali, A. S.; Abdelhamid, A. O. Bull Chem Soc Jpn
1976, 49, 321.
[19] Abdelhamid, A. O.; El-Shiatey, F. H. H. Phosphorus
Sulfur Silicon Relat Elem 1988, 39, 45.
[20] Abdelhamid, A. O.; Attaby, F. A.; Khalifa, F. A.;
Ghabrial, S. S. Arch Pharm Res 1992, 15, 14.
[21] Hassaneen, H. M.; Shawali, A. S.; Elwan, N. M.;
Abounada, N. M. Sulfur Lett 1992, 14, 41.
REFERENCES
[1] Part 35: Rateb, N. M.; Abdel-Riheem, N. A.; Al-Atoom,
A. A.; Abdelhamid, A. O. Phosphorus, Sulfur Silicon
Relat Elem (in press).
[2] Padwa, A. Angew Chem, Int Ed Engl 1976, 15, 123.