Reactions of hydrazonoyl halides 471: Synthesis of some new 2,3-dihydro-1,3,4-thiadiazoles, triazolo[4,3-a]pyrimidines, and pyrazolo[3,4-d]pyridazines with expected biological activity

Article abstract of DOI:10.1080/10426500500272079

2,3-dihydro-1,3,4-thiadiazoles, triazolino[4,3-a] pyrimidines , andpyrazolo [3,4-d]pyridazines were synthesized in good yields from reactions of hydrazonoyl halides with alkyl carbodithioates, pyrimidine-2-thione, and substituted prop-2-ene-1-one, respect

Full text of DOI:10.1080/10426500500272079

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Phosphorus, Sulfur, and Silicon
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Reactions of Hydrazonoyl
Halides 47: Synthesis of
Some New 2,3-dihydro-1,3,4-
thiadiazoles, Triazolo[4, 3-
a]pyrimidines, and Pyrazolo[3,
4-d]pyridazines with Expected
Biological Activity
Yasser H. Zaki a , Sayed A. Ahmed a , Ahmed M.
Hussein a & Abdou O. Abdelhamid b
a Department of Chemistry, Cairo University (Beni-
Suef Branch), Beni-Suef, Egypt
b Department of Chemistry, Cairo University, Giza,
Egypt
Published online: 15 Aug 2006.
To cite this article: Yasser H. Zaki , Sayed A. Ahmed , Ahmed M. Hussein & Abdou
O. Abdelhamid (2006) Reactions of Hydrazonoyl Halides 47: Synthesis of Some New
2,3-dihydro-1,3,4-thiadiazoles, Triazolo[4, 3-a]pyrimidines, and Pyrazolo[3, 4-
d]pyridazines with Expected Biological Activity, Phosphorus, Sulfur, and Silicon and
the Related Elements, 181:4, 825-837, DOI: 10.1080/10426500500272079
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Phosphorus, Sulfur, and Silicon, 181:825–837, 2006
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500500272079
Reactions of Hydrazonoyl Halides 471: Synthesis
of Some New 2,3-dihydro-1,3,4-thiadiazoles,
Triazolo[4,3-a]pyrimidines, and
Pyrazolo[3,4-d]pyridazines with Expected
Biological Activity
Yasser H. Zaki
Sayed A. Ahmed
Ahmed M. Hussein
Department of Chemistry, Cairo University (Beni-Suef Branch),
Beni-Suef, Egypt
Abdou O. Abdelhamid
Department of Chemistry, Cairo University, Giza, Egypt
2,3-dihydro-1,3,4-thiadiazoles, triazolino[4,3-a]pyrimidines, and pyrazolo[3,4-
d]pyridazines were synthesized in good yields from reactions of hydrazonoyl halides
with alkyl carbodithioates, pyrimidine-2-thione, and substituted prop-2-ene-1-one,
respectively. All structures of the newly synthesized compounds were elucidated by
elemental analysis, spectral data, and an alternative synthesis method. Some of the
new compounds were tested towards bacteria and fungi.
Keywords 2,3-Dihydro-1,3,4-thiadiazolines; cycloaddition; pyrazolo[3,4-d]pyridazines;
triazolino[4,3-a]pyrimidines
INTRODUCTION
1,3,4-thiadiazoles have activities on many biological systems such
as antitumor,2 and hypoglycemic properties,3 antihistamine4 and
anticholinergic.5 Also, triazolopyrimidines have been reported to ex-
hibit in vivo leisshmanicidal activity against the mistigate stage of
Leishmaniadonovani6,7 and cardiovascular activity.8,9 Also, thiadia-
zoles are cardiotonics and coronary vasadilatores, and they have an-
tihypertensive properties.10 As an extension of our study11−18 and as
Received February 24, 2005; accepted April 7, 2005.
Address correspondence to Abdou O. Abdelhamid, Cairo University, Department of
Chemistry, Faculty of Science, Giza 12316, Egypt. E-mail: Abdou abdelhamid@yahoo.
com
825

826
Y. H. Zaki et al.
a part of our program aiming at the synthesis of different hetero-
cyclic derivatives, we report here the utility of C-(2,4-dimethyl)thiazol-
5-yl-N-arylhydrazonoyl bromides 1a and 1b in the synthesis of
some 2,3-dihydro-1,3,4-thiadiazoles, triazolino[4,3-a]pyrimidines, and
pyrazolo[3,4-d]pyridazines.
RESULTS AND DISCUSSION
Treatment of C-(2,4-dimethyl)thiazol-5-yl-N-phenylhydrazononoyl bro-
mide (1a) with methyl phenyldithiocarbamate (3)19 in ethanolic tri-
ethylamine at r.t. gave one isolable product, evidenced by tlc, whose
structure seemed to be either 4 or 5 (Scheme 1). Its IR spectrum re-
vealed bands at 3060, 2923 (CH), 1634 (CO conjugated), 1593 (C C)
and no absorption band near 2100–2300 cm−1 due the absence of C S.
1H NMR showed signals at δ = 2.76 (s, 3H), 2.79 (s, 3H) and 7.08–7.92
(m, 10H). On the basis of elemental and spectral data, the product was
formulated as: 2-(azaphenylmethylene)-3-phenyl-(1,3,4-thiadiazolin-5-
yl)-2,4-dimethylthiazol-5-yl ketone (4a).
SCHEME 1
Two possible pathways can account for the formation of 4: (1) 1,3-
the addition of the thiol isomer 3 to the hydrazonoyl bromide 1a (or
carbene 2a, which was prepared in situ from 1a and triethylamine) to
afford 4 via the elimination of methyl mercaptan, and (2) alternatively,
the 1,3-cycloaddition of the carbene 2a to the C S. Similarly, 1b reacted
with 2 to afford 3b in a good yield (Scheme 1).

Reactions of Hydrazonoyl Halides 47
827
Similarly, the appropriate 1a,b reacted with the appropriate methyl
carbodithiates 6–9 in ethanolic triethylamine to give 2,3-dihydro-1,3,4-
thiadiazole derivatives 10–13(a,b), respectively (Scheme 2).
SCHEME 2
The treatment of the appropriate hydrazonoyl bromide 1a and 1b
with 2-mercapto-5-phenyl-1,3,4-oxadiazole (14) and triethylamine in
boiling chloroform under reflux gave N-(aza{5-[(2,4-dimethylthiazol-
5-yl)carbonyl]-3-substituted 1,3,4-thiadiazolin-2-ylidene}-methylben-
zamide 17a and 17b, respectively. Structure 17 was elucidated on the
base of elemental analyses, spectral data, and an alternative synthe-
sis method. Thus, the treatment of each 1a and 1b with the appro-
priate methyl benzoylhydrazinecarbodithioate 18a (or ethyl benzoyl-
hydrazinecarbodithioate (18b)) in ethanolic triethylamine afforded a
product identical in all respects (m.p., mixed m.p., and spectra) with
17a and 17b, respectively.
In the light of the foregoing results, the mechanism outlined in
Scheme 3 seems to be the most plausible pathway for the formation
of 17 from the reaction 1 with 5-phenyl-1,3,4-oxadiazole-2-thione (14).
The reaction involves an initial formation of the thiohydrazonate ester
15, which undergoes intramolecular cyclization as soon as it is formed
to yield the spirothiadiazole intermediate 16 or via the cycloaddition
of carbene 2 to the C S double bond of 14. The formation of 15 and
16 are similar to the reaction of hydrazonoyl chloride with 5-phenyl-
1,3,4-thiadiazloe-2(3H)-thione20 and 1-phenyl-1,4-dihydrotetrazle-5-
thione.21 Alternatively, the formation of 17 can be explained via the
elimination of alkyl mercaptan from the cycloadduct 19.
Next, the treatment of 6-oxo-4-phenyl-2-thioxo-1,3-dihydropyri-
midine-5-carbonitrile (20)22 with 1a in boiling chloroform containing
triethylamine, a single product was isolated. The products were cha-
racterized as 3-[(2,5-dimethyl(1,3-thiazol-4-yl))carbonyl]-4-oxo-1,6-di-
phenyl-3a-hydro-1,2,4-triazolino[4,3-a]pyrimidine-5-carbonitrile (26a)

828
Y. H. Zaki et al.
SCHEME 3
(Scheme 4) on the basis of elemental analysis, spectral data, and an
alternative synthesis route. Thus, 1a reacted with 2822 in ethanolic tri-
ethylamine and to give a product identical in all respects (m.p., mixed
m.p., and spectra) with 26a.
The reaction pathway accounting for the formation of 26 from 1 and
20 is outlined in Scheme 4. It is proposed that the reaction involves
an initial 1,3-addition to give intermediates 21–23 or cycloaddition to
afford intermediate 24, which undergo a Smiles rearrangement to the
thiohydrazide 25. The latter then cyclizes with the concurrent elimina-
tion of hydrogen sulfide to give the final product, which has a structure
of either 26 or isomer 27.
The actual structure of the products was found to resemble 26
by their IR spectra and M.O. calculation. For example, the carbonyl
stretching frequencies of 26 (1701–1705 cm−1) were found to be near
the structure 29 (1680–1705 cm−1) and not 30 (1640–1660 cm−1
)
(Scheme 5).23,24 According to the M.O. calculation, using the Hyper
Chem. AM1 semiemperical method, the total energy of structure 26
(E = −5602.0029 K Cal) is higher than isomer 27 (E = −5561.7051
K Cal). These data proved structure that 26 is the most stable isomer
(Scheme 4).

Reactions of Hydrazonoyl Halides 47
829
SCHEME 4
SCHEME 5
Finally, the treatment of the 5-acetyl-4-methyl-2-phenylthiazole 31
with dimethylformamide-dimethylacetal in boiling dry xylene under
reflux gave 3-(dimethylamino)-1-(4-methyl-2-phenyl(1,3-thiazol-5-
yl))prop-2-ene-1-one (32) in good yield. Structure 32 was confirmed

830
Y. H. Zaki et al.
on the basis of elemental analysis, spectral data, and chemical trans-
1
formation. Thus, the H NMR spectrum of 32 showed signals at 2.79
(s, 3H), 2.92 (s, 3H), 3.11 (s, 3H), 5.43–5.64 (d, 1H), 6.95–7.18 (d,
1H) and 7.41–8.01 (m, 5H). Thus, the treatment of C-ethoxycarbonyl-
N-phenylhydrazonoyl chloride 33a with 32 in refluxing toluene
containing triethylamine yielded one isolable product, evidenced by
TLC, which formulated either ethyl 3-[(4-methyl-2-phenyl(1,3-thiazol-
5-yl))carbonyl]-1-phenylpyrazole-4-carboxylate (37a) or ethyl 3-[(4-
methyl-2-phenyl(1,3-thiazol-5-yl))carbonyl]-1-phenylpyrazole-5-carbo-
xylate (38a) (Scheme 6).
SCHEME 6
Some of the newly synthesized compounds were tested toward
Bacillus Ccereus (-ve bacteria) and Fusarium Oxysporum (fungal-plant
pathogens) in CHCl3 using the filter paper and hole plate method 26.

Reactions of Hydrazonoyl Halides 47
831
The formation of 37 can be explained via the reaction of nitrilum
imide 34, which formed in situ from hydrazonoyl halides and tri-
ethylamine, with 32 to afford the cyclo adduct intermediate 35 or 36
and then eliminate diethylamine to give pyazole as final product 37
or pyrazole 38. Similarly, the appropriate hydrazonoyl halides 33b–
e reacted with the appropriate 32 to afford corresponding pyrazoles
37b–e.
Pyrazolo[3,4-d]pyridazines 39a–d were obtained in a good yield from
boiling the appropriate pyrazoles 37a–e with hydrazine hydrate in
boiling ethanol (Scheme 6). Structure 39 was elucidated on the ba-
sis of elemental analysis, spectral data, and the alternative synthesis
1
route. The H NMR spectrum of 39b showed signals at δ = 2.86 (s,
3H), 3.01 (s, 3H), 7.13–8.00 (m, 10 H), and 8.66 (s, 1H, pyrazole C-5).
Compound 37d reacted with hydrazine hydrate in boiling ethanol to
give an identical product in all respects (m.p., mixed m.p., and spectra)
with 39a.
Antimicrobial Activity
The tested microorganisms were gram −ve bacteria (Bacillus cereus).
In addition, some fungal-plant pathogens (Fusarium Oxysporum) were
tested. The sensitivity of the selected microorganisms to some synthe-
sized compounds was determined in vitro culture in CHCl3.The tests
were carried out using the filter paper and hole plate method.25
Studies on the biological activity of compounds 39b show that these
compounds have negative biological activity against the tested bacteria,
whereas 13a, 13b, and 15a have moderate to weak biological activity
against the tested bacteria. Compounds 14b, 15b, and 35d have strong
activity against the tested bacteria (Table I). Finally, compound 37d has
strong antifungl activity, whereas compound 39c has weak antifungal
activity.
EXPERIMENTAL
All melting points were determined on an electrothermal apparatus and
are uncorrected. IR spectra were recorded (KBr discs) on a Shimadzu
1
FT-IR 8201 PC spectrophotometer. H NMR spectra were recorded in
CDCl3 and (CD3)2SO solutions on a Varian Gemini 300 MHz spec-
trometer, and chemical shifts are expressed in δ units using TMS as
an internal reference. Elemental analyses and antimicrobial were car-
ried out at the Microanalytical Center of the Cairo University, Giza,
Egypt.

832
Y. H. Zaki et al.
TABLE I Response of Various Microorganisms
to Some Synthesized Compounds In Vitro
(Culture)
Antibacterial activity
(% inhibition)
Antifungal activity
(% inhibition)
Compound no.
13a
13b
14b
15a
15b
37d
39b
39c
24.5
22.2
100.0
20.0
90.0
68.0
0.0
0.0
0.0
0.0
0.0
0.0
60.0
8.8
30.0
34.0
Synthesis of (2,4-Dimethyl-1,3-thiazol-5-yl)[(5E)-4-phenyl-5-
(phenylimino)-4,5-dihydro-1,3,4-thiadiazol-2-yl]methanone
(4a) and (2,4-Dimethyl-1,3-thiazol-5-yl)[(5E)-4-(4-
methylphenyl)-5-(phenylimino)-4,5-dihydro-1,3,4-thiadiazol-
2-yl]methanone (4b)
An equimolar amount of the appropriate hydrazonoyl bromides26 1a or
1b, methyl phenyldithiocarbamate 3, and triethylamine (5 mmol each)
in ethanol (10 mL) were stirred for 2 h at r.t. The resulting solids were
collected by filtration and crystallized from ethanol to give red crystals
4a and 4b, respectively (Tables II and III).
Synthesis of 2,3-Dihydro-1,3,4-thiadiazoline Derivatives
10–13(a,b)
An equimolar amount of the appropriate hydrazonoyl bromides 1a or
1b, the appropriate of methyl carbodithiates 6–913,15,27,28 and triethy-
lamine (5 mmol each) in ethanol (10 mL) were stirred for 2 h at r.t. The
resulting solids were collected by filtration and crystallized from dioxan
to give (10–13)a,b respectively (Tables II and III).
Synthesis of N-(Aza{5-[(2,4-dimethylthiazol-5-yl))carbonyl]-
3-substituted 1,3,4-thiadiazolin-2-ylidene}methylbenzamide
17a and 17b
Method A
An equimolar amount of the appropriate hydrazonoyl bromides
1a or 1b, the appropriate alkyl benzoylhydrazinecarbodithiate, and
triethylamine (5 mmol each) in ethanol (10 mL) were stirred for 2 h

Reactions of Hydrazonoyl Halides 47
833
TABLE II Characterization Data of the Newly Synthesized
Compounds
% Analyses calcd./found
Compound
no.
M.P., ◦
solvent
C
Color
yield %
Mol. formula
mol. wt
C
H
N
S
4a
195–197
EtOH
175–177
EtOH
Red
78
Red
75
Brown
83
Yellow
80
Brown
74
Yellow
79
Red
88
Red
85
Brown
79
Red
77
Red
78
Red
75
Brown
78
Brown
74
Yellow
84
Yellow
80
Yellow
78
Yellow
83
Pale red
74
Red
75
Yellow
81
Yellow
85
Yellow
80
Yellow
77
C20H16N4OS2
392.49
C21H18N4OS2
406.52
C23H15N5OS3
473.59
C24H17N5OS3
487.62
C24H18N6OS2
470.57
C25H20N6OS2
484.59
C18H15N5O2S2
397.47
C19H17N5O2S2
411.50
61.20
61.13
62.04
61.95
58.33
58.29
59.11
59.07
61.26
61.30
61.96
62.00
54.39
54.40
55.46
55.42
60.87
60.92
61.58
61.61
57.91
57.96
58.78
58.74
63.71
63.66
64.36
64.40
66.15
66.00
66.17
66.20
68.20
68.23
72.14
72.18
69.81
69.80
68.11
68.15
65.44
65.47
68.91
68.88
72.79
72.81
68.61
68.45
4.11
4.01
4.46
4.52
3.19
3.15
3.51
3.54
3.86
3.84
4.16
4.19
3.80
3.77
4.16
4.18
4.04
3.99
4.34
4.30
3.93
4.00
4.26
4.29
3.56
3.52
3.89
3.94
5.92
5.88
4.59
4.57
4.42
4.46
4.26
4.22
4.34
4.36
4.06
3.99
3.92
3.90
4.47
4.45
4.30
4.27
4.09
3.89
14.27
14.33
13.78
13.90
14.79
14.76
14.36
14.32
17.86
17.92
17.34
17.30
17.62
17.66
17.02
16.98
14.79
14.76
14.36
14.33
16.08
16.02
15.58
15.53
18.57
18.60
18.01
17.08
10.28
10.32
10.06
10.10
10.84
10.81
9.35
16.34
16.29
15.77
15.72
20.31
20.36
19.73
19.77
13.63
13.58
13.23
13.22
16.13
16.17
15.58
15.61
13.54
13.58
13.15
13.21
14.72
14.79
14.26
14.33
7.09
7.05
6.87
6.85
11.77
11.71
7.68
7.65
8.28
8.30
7.13
7.15
6.90
4b
10a
10b
11a
11b
12a
12b
13a
13b
17a
17b
26a
26b
32
>300
Dioxan
293–295
Dioxan
>300
Dioxan
273–276
Dioxan
>300
Dioxan
>300
Dioxan
265–267
Dioxan
295–297
Dioxan
280–283
Dioxan
252–254
Dioxan
195–197
EtOH
180–183
EtOH
122–124
EtOH
159–161
EtOH
140–142
EtOH
178–180
EtOH
245–247
EtOH
150–152
EtOH
276–278
EtOH
213–215
EtOH
222–224
EtOH
212-215
EtOH
C24H19N5O2S2
473.57
C25H21N5O2S2
487.59
C
21H17N5O2S2
435.52
C22H19N5O2S2
449.55
C24H16N6O2S
452.48
C25H18N6O2S
466.51
C15H16N2OS
272.36
C23H19N3O3S
417.48
C22H17N3O2S
387.45
C27H19N3O2S
449.52
C27H20N4O2S
464.53
C31H22N4O2S2
546.66
C21H15N5OS
385.44
C22H17N5S
383.47
C27H19N5S
445.53
37a
37b
37c
37d
37e
39a
39b
39c
39d
9.36
12.06
12.01
10.25
10.21
18.17
18.18
18.26
18.30
15.72
15.76
15.49
15.70
6.88
11.73
11.78
8.32
8.30
8.36
8.38
7.20
7.17
11.82
11.58
C31H22N6S2
542.67

834
Y. H. Zaki et al.
TABLE III Spectra of Some Newly Synthesized Compounds
Compound
no.
Spectral data
4a
IR: 3060, 2923 (CH), 1634 (CO conjugated) and 1593 (C C).
1H NMR: 2.76 (s, 3H), 2.79 (s, 3H) and 7.08–7.92 (m, 10H).
IR: 3030, 2917 (CH), 1621 (CO conjugated) and 1583 (C C).
1H NMR: 2.17 (s, 3H), 2.47 (s, 3H), 2.79 (s, 3H) and 7.08–7.92 (m, 9H).
IR: 3006, 2912 (CH), 2192 (CN) and 1651(CO conjugated).
1H NMR: 2.69 (s, 3H), 2.84 (s, 3H) and 7.25–7.99 (m, 9H).
IR: 3057, 2921 (CH), 2193 (CN) and 1655 (CO conjugated).
1H NMR: 2.39 (s, 3H), 2.47 (s, 3H), 2.71 (s, 3H) and 7.32–7.96 (m, 8H).
IR: 3037, 2924 (CH), 2193 (CN) and 1647 (CO conjugated).
1H NMR: 2.49 (s, 3H), 2.82 (s, 3H), 3.78 (s, 3H) and 7.26–7.74 (m, 9H).
IR: 3001, 2909 (CH), 2183 (CN) and 1622 (CO conjugated).
1H NMR: 2.35 (s, 3H), 2.47 (s, 3H), 2.75 (s, 3H), 3.72 (s, 3H) and
7.26–7.41 (m, 8H).
4b
10a
10b
11a
11b
12a
12b
IR: 3320 (NH), 3020, 2949 (CH), 1705, 1659 (CO’s) and 1594 (C C).
1H NMR: 1.11 (s, 3H), 2.53 (s, 3H), 2.75 (s, 3H), 7.42–7.74 (m, 5H) and
11.4 (s, 1H).
IR: 3317 (NH), 3021, 2940 (CH), 1710, 1658 (CO’s) and 1590 (C C).
1H NMR: 1.09 (s, 3H), 2.35 (s, 3H), 2.50 (s, 3H), 2.74 (s, 3H), 7.46–7.69
(m, 4H) and 11.6 (s, 1H).
13a
13b
IR: 3061, 2920 (CH), 1705, 1653 (CO’s) and 1604 (C C).
1H NMR: 1.24 (s, 3H), 2.46 (s, 3H), 2.72 (s, 3H) and 7.11–8.01 (m, 10H).
IR: 3064, 2924 (CH), 1705, 1657 (CO) and 1609 (C C).
1H NMR: 1.23 (s, 3H), 2.35 (s, 3H), 2.46 (s, 3H), 2.80 (s, 3H) and
7.11–8.00 (m, 9H).
17a
17b
IR: 3314 (NH), 3010, 2929 (CH), 1659 (CO) and 1593 (C C).
1H NMR: 2.43 (s, 3H), 2.75 (s, 3H), 7.22–7.94 (m, 10H) and 11.6 (s, 1H).
IR: 3304 (NH), 2979, 2923 (CH), 1655 (CO) and 1597 (C C).
1H NMR: 2.32 (s, 3H), 2.46 (s, 3H), 2.74 (s, 3H), 7.29–7.91 (m, 9H) and
11.4 (s, 1H).
26a
26b
32
IR: 3080, 2920 (CH), 2217, (CN), 1705 (CO), 1654 (CO conjugated) and
1594 (C C).
1H NMR: 2.47 (s, 3H), 2.74 (s, 3H) and 7.24–8.05 (m, 10H).
IR: 3070, 2925 (CH), 2220, (CN), 1701 (CO), 1657 (CO conjugated) and
1589 (C C).
1H NMR: 2.35 (s, 3H), 2.49 (s, 3H), 2.78 (s, 3H) and 7.24–8.05 (m, 9H).
IR: 2904 (CH) and 1655 (CO conjugated).
1H NMR: 2.79 (s, 3H), 2.92 (s, 3H), 3.11 (s, 3H), 5.43–5.64 (d, 1H),
6.95–7.18 (d, 1H) and 7.41–8.01 (m, 5H).
37a
37b
IR: 3059, 2980 (CH), 1708 (CO), 1649 (CO conjugated) and 1598 (C C).
1H NMR: 1.18 (t, 3H, OCH2CH3), 2.75 (s, 3H), 4.25 (q, 2H, OCH2CH3),
7.38–7.95 (m, 10H, ArH’s) and 8.26 (s, 1H, pyrazole C-5).
IR: 3035, 2981 (CH), 1645 (CO conjugated) and 1597 (C C).
1H NMR: 2.47 (s, 3H), 2.55 (s, 3H), 7.25–7.95 (m, 10H, ArH’s) and 8.20 (s,
1H, pyrazole C-5).
(Continued on next page)

Reactions of Hydrazonoyl Halides 47
835
TABLE III Spectra of Some Newly Synthesized Compounds
(Continued)
Compound
no.
Spectral data
37c
IR: 3059, 2923 (CH), 1643 (CO conjugated) and 1597 (C C).
1H NMR: 2.49 (s, 3H), 7.25–8.19 (m, 15H, ArH’s) and 8.36 (s, 1H, pyrazole
C-5).
37d
37e
39a
39b
IR: 3432 (NH), 3061, 2983 (CH), 1673 (CO) and 1592 (C C).
1H NMR: 2.46 (s, 3H), 7.13–7.87 (m, 15H, ArH’s), 8.36 (s, 1H, pyrazole C-5)
and 10.79 (s, 1H).
IR: 3052, 2970 (CH), 1661 (CO) and 1581 (C C).
1H NMR: 2.43 (s, 3H), 2.45 (s, 3H), 7.22–7.96 (m, 15H, ArH’s) and 8.27 (s,
1H, pyrazole C-5).
IR: 3448 (NH), 3080, 2997 (CH), 1679 (CO) and 1587 (C C).
1H NMR: 2.69 (s, 3H), 7.26–8.02 (m, 10H, ArH’s), 8.50 (s, 1H, pyrazole C-5)
and 10.19 (s, 1H).
IR: 3045, 2991 (CH) and 1587 (C C).
1H NMR: 2.86 (s, 3H), 3.01 (s, 3H), 7.13–8.00 (m, 10 H, ArH’s), 8.66 (s, 1H,
pyrazole C-5.
39c
39d
IR: 3052, 2956 (CH) and 1591 (C C).
1H NMR: 2.94 (s, 3H), 7.25–8.78 (m, 15 H, ArH’s), 8.85 (s, 1H, pyrazole C-5.
IR: 3052, 2956 (CH) and 1591 (C C).
1H NMR: 2.35 (s, 3H), 2.47 (s, 3H), 7.32–7.48 (m, 15H), 7.78 (s, 1H, pyrazole
C-5.
at r.t. The resulting solids were collected and crystallized from dioxan
to give red crystal 17a and 17b, respectively (Tables II and III).
Method B
A mixture of the appropriate hydrazonoyl bromides 1a or 1b (5 mmol)
and 2-mercapto-5-phenyl-1,3,4-oxadiazole 14 (0.84 g, 5 mmol) in chlo-
roform (20 mL) containing triethylamine (0.5 g (0.75 mL), 5 mmol) were
refluxed for 10 h; chloroform was evaporated under reduced pressure
and the residue solids were collected and crystallized to give products
identical in all respects (m.p., mixed m.p., and spectra) with correspond-
ing products obtained by Method A.
Synthesis of 3-[(2,5-Dimethyl(1,3-thiazol-4-yl))carbonyl]-4-
oxo-1,6-diphenyl-3a-hydro-1,2,4-triazolino[4,3-a]pyrimidine-
5-carbonitrile (26a) and (26b)
Method A
A mixture of the appropriate hydrazonoyl bromides 1a or 1b (5 mmol)
and 6-oxo-4-phenyl-2-thioxo-1,3-dihydropyrimidine-5-carbonitrile (22)

836
Y. H. Zaki et al.
(1.145 g, 5 mmol) in chloroform (20 mL) containing triethylamine (0.5 g
(0.75 mL), 5 mmol) was refluxed for 10 h; chloroform was evaporated
under reduced pressure and the residue solid was collected and crys-
tallized to give 26a and 26b (Tables II and III).
Method B
An equimolar amount of the appropriate hydrazonoyl bromides 1a or
1b, 2-(methylthio)-6-oxo-4-phenyl-,6-dihydropyrimidine-5-carbonitrile
(28), and sodium ethoxide (5 mmol each) in ethanol (20 mL) was re-
fluxed for 3 h. The reaction mixture was cooled and the resulting
solid was collected and crystalized to give products identical in all re-
spected (m.p., mixed m.p., and spectra) with the appropriate 26a or
26b.
Synthesis of 3-(Dimethylamino)-1-(4-methyl-2-phenyl(1,3-
thiazol-5-yl))prop-2-ene-1-one (32)
A mixture of 5-acetyl-4-methyl-2-phenylthiazole (31) (2.17 g, 10 mmol)
and dimethylformamide-dimethylacetal (1.47 g, 10 mmol) were refluxed
in dry xylene (10 mL) for 4 h. The hot solution was evaporated to its
half volume and then cooled. The resulting solid was collected and crys-
tallized to give 32 (Tables I and II).
Synthesis of 1-Phenyl-4-(4-methyl-2-phenyl)thiazol-5-yl-
3-substituted Pyrazoles 37a–e
An equimolar amount of each of the appropriate 32 and appropriate
hydrazonoyl halides 33a–e (0.005 mole) were refluxed in dry toluene
containing triethylamine for 3 h. The hot solution was filtered off and
the filtrate was evaporated and triturated with petroleum ether (40–
60◦C). The resulting solid was collected and crystallized from ethanol
to give 37a–e, respectively (Tables I and II).
Synthesis of Pyrazolo[3,4-d]pyridazines 39a–d
An appropriate of 1-phenyl-4-phenylcarbonyl-3-substituted pyrazoles
37a–e (0.5 g) and hydrazine hydrate (1 mL) in ethanol (15 mL) were
refluxed for 1 h. The resulting solid was collected and crystallized
to give the corresponding pyrazolo[3,4-d]pyridazines 39a–d (Tables I
and II).

Reactions of Hydrazonoyl Halides 47
837
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