Reactions of hydrazonoyl halides 41:1 Synthesis of 1,2,4-triazoles, 2,3-dihydro-1,3,4-thiadiazoles, and triazolo[4,3-a]pyrimidines

Article abstract of DOI:10.1080/104265090917448

Triazoles, thiadiazoles, and triazolo[4,3-a]pyrimidines were synthesized via reaction of hydrazonoyl halides with each of 3-methyl-4- (methylthiothioxomethyl)-2-pyrazolin-5-one, 3-methyl-4-[methylthio(phenylamino) methyl]-2-pyrazolin-5-one, and pyrimidine

Full text of DOI:10.1080/104265090917448

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Reactions of Hydrazonoyl
Halides 41: Synthesis of 1,2,4-
Triazoles, 2,3-Dihydro-1,3,4-
thiadiazoles, and Triazolo[4, 3-
a]pyrimidines
Abdou O. Abdelhamid a , Ahmed H. Elghandour b ,
Ahmed M. Hussein b & Yasser H. Zaki b
a Department of Chemistry , Faculty of Science,
Cairo University (Beni-Suef Branch) , Beni-Suef,
Egypt
b Department of Chemistry , Faculty of Science,
Cairo University , Giza, Egypt
Published online: 19 Aug 2006.
To cite this article: Abdou O. Abdelhamid , Ahmed H. Elghandour , Ahmed M.
Hussein & Yasser H. Zaki (2005) Reactions of Hydrazonoyl Halides 41: Synthesis of
1,2,4-Triazoles, 2,3-Dihydro-1,3,4-thiadiazoles, and Triazolo[4, 3-a]pyrimidines,
Phosphorus, Sulfur, and Silicon and the Related Elements, 180:9, 2097-2109, DOI:
10.1080/104265090917448
To link to this article: http://dx.doi.org/10.1080/104265090917448
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Phosphorus, Sulfur, and Silicon, 180:2097–2109, 2005
Copyright © Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/104265090917448
Reactions of Hydrazonoyl Halides 41:1 Synthesis
of 1,2,4-Triazoles, 2,3-Dihydro-1,3,4-thiadiazoles,
and Triazolo[4,3-a]pyrimidines
Abdou O. Abdelhamid
Department of Chemistry, Faculty of Science, Cairo University,
Giza, Egypt
Ahmed H. Elghandour
Ahmed M. Hussein
Yasser H. Zaki
Department of Chemistry, Faculty of Science, Cairo University
(Beni-Suef Branch), Beni-Suef, Egypt
Triazoles, thiadiazoles, and triazolo[4,3-a]pyrimidines were synthesized via reac-
tion of hydrazonoyl halides with each of 3-methyl-4-(methylthiothioxomethyl)-2-
pyrazolin-5-one, 3-methyl-4-[methylthio(phenylamino)methyl]-2-pyrazolin-5-one,
and pyrimidine-2-thiones. Structures of the newly synthesized compounds were elu-
cidated on the basis of elemental analysis, spectral data, and alternative-methods
synthesis whenever possible.
Keywords 1,2,4-Triazoles; 2,3-dihydro1,3,4-thiadiazolines; hydrazonoyl halides;
triazolino[4,3-a]pyrimidines
INTRODUCTION
1,2,4-Triazoles display biological activity such as inhibition of
cholinesterase, interference with mitosis, and reversible denaturation
of serum proteins.2 1,3,4-thiadiazole and its derivatives have become
very useful compound in medicine, agriculture, and in many fields
of technology.3 As an extension of our study4−9 and as a part of our
program aiming at the synthesis of different 1,2,4-triazoles and 2,3-
dihydro-1,3,4-thiadiazoles for medicine, we report here the reactivity
of hydrazonoyl halides toward some alkyl carbodithioates, thioanilides,
and dihydropyrmidine-2-thiones derivatives.
Received July 24, 2004; accepted October 25, 2004.
Address correspondence to Abdou O. Abdelhamid, Cairo University, Department of
Chemistry, Faculty of Science, Giza 12613, Egypt. E-mail: abdou abdelhamid@yahoo.
com
2097

2098
A. O. Abdelhamid et al.
RESULTS AND DISCUSSION
Treatment of methyl isothiocyanate with each of 3-methyl-2-
pyrazolin-5-one (1a) or 3-methyl-1-phenyl-2-pyrazolin-5-one (1b)
in N,N-dimethylformamide containing potassium hydroxide afforded
3-methyl-4-(methylthiothioxomethyl)-2-pyrazolin-5-one (2a) and 3-
methyl-4-(methylthiothioxomethyl)-1-phenyl-2-pyrazolin-5-one (2b),
respectively. Structure 2 was elucidated by elemental analysis, spectral
1
data, and chemical transformation. H NMR spectrum of 2a showed
signals at δ = 2.25 (s, 3H), 3.22 (s, 3H), 5.26 (s, 1H), 9.88 (s, br., 1H),
11.10 (s, br., 1H), and 1H NMR spectrum of 2b showed signals at
δ = 2.17 (s, 3H), 3.32 (s, 3H|), 5.26 (s, 1H), 7.26–7.42 (m, 3H), 7.77–7.81
(d, 2H) and 10.85 (s, br., 1H). The appropriate 1a or 1b reacted with
phenyl isothiocyanate to give 2c10,11 and 2d,10,11 respectively. Also,
each 3a10,13 and 3b that reacted with aniline in boiling ethanol have
products identical in all respects (mp., mixed mp., and spectra) with
2c and 2d, respectively.
Compound 4a10 was obtained via methylation of 2d or by the re-
action of 4-(dimethylthiomethylene)-3-methyl-1-phenyl-2-pyrazolin-5-
one (5)12 with aniline. By a similar route, compound 5 reacted with the
appropriate p-toluidene and benzylamine to give 4b and 4c, respec-
tively (Scheme 1). Structures 4b and 4c were elucidated by elemental
analysis and spectral and chemical transformation.
SCHEME 1

Reactions of Hydrazonoyl Halides 411
2099
Treatment of the appropriate C-methoxycarbonyl-N-phenylhydra-
zonoyl chloride 6a with 2a in ethanolic triethylamine at room temper-
ature afforded one isolable product 17a. 1H NMR spectrum of the prod-
uct showed signals 1.04 (s, 3H), 3.95 (s, 3H), 7.46–7.80 (m, 5H, ArH’s),
and 11.26 (s, 1H, NH). Compound 6a reacted with each of 2c or 3a in
ethanolic triethylamine to afford a product identical in all respects (mp.,
mixed mp., and spectra) with 17a.
Also, treatment the appropriate of 2a (3a) and 2b (or 2c–d, 3b)
with the appropriate hydrazonoyl halides 6–13(a–c) in ethanolic
triethylamine afforded 2,3-dihydro-1,3,4-thiadiazoles 17–24(a–c) and
25–32(a–c), respectively (Scheme 2). Structures 17–24 and 25–32 were
confirmed on the basis of elemental analysis and spectral data. Thus,
1H NMR spectrum of 25a showed signals at δ = 1.29 (s, 3H), 4.04
(s, 3H), 7.26–7.30 (m, 3H), 7.60 (s, 5H), and 7.88–8.03 (d, 2H).
SCHEME 2

2100
A. O. Abdelhamid et al.
Two possible pathways can account for the formation of 17a (1) 1,3-
addition of the thiol isomer 3a to the hydrazonoyl chloride 6a (or nitril-
ium imide 14a, which is prepared in situ from 6a and triethylamine)
can give the thiohydrazonate ester 15, which undergoes nucleophilic
cyclization to yield 16, which then affords 17a by loss of CH3SH and
(2) alternatively, 1,3-cycloaddition of the nitrilum imide 14a to the C S
of 3a can give 16a, which converted to 17a via elimination of CH3SH
(Scheme 2).
Sterochemically, the isolated products can have either the configu-
ration A or B. According to M. O. Calculation, using the Hyper Chem.
AM1 semiemperical method, the total energy proved that the most sta-
ble isomer formulated as B as shown (Scheme 3):
SCHEME 3
Treatment of 4a with C-ethoxycarbonyl-N-phenylhydrazonoyl chlo-
ride (7a) in boiling ethanolic triethylamine under reflux gave
ethyl 5-(3-methyl-5-oxo-1-phenyl(2-pyrazolin-4-ylidene))-1,4-diphenyl-
1,2,4-triazoline-3-carboxylate (35a) in good yield. Structure 35 was con-
firmed on the basis of elemental analysis and spectral data (Scheme 4).
Thus, 1H NMR spectrum of 35a showed signals at δ = 1.28 (s, 3H), 1.31
(t, 3H), 4.12 (q, 2H) and 7.21–7.89 (m, 15H). 13C NMR spectrum of 35a
is shown in Scheme 4.
Treatment of the appropriate hydrazonoyl halides 7a–10a with each
of 4a–c under the same condition afforded 1,2,4-triazolin-5-ylidene-2-
pyrazolin-5-one derivatives 35–38(a–c), respectively. Mass spectrum of
38a revealed peaks at m/z (%) = 512 (12), 328 (33), 206 (46.9), 200 (42.5),
181 (19.8), 180 (32.3), 119 (31), 108 (11), 104 (56), and 77 (100).
Treatment of the appropriate hydrazonoyl halides 7a–10a with
each of ethyl 4-methyl-5-substituted-2-thioxo-1,3,6-trihydropyridine-
5-carboxylates 39a and 39b in boiling chloroform containing trietyh-
lamine under reflux, which afforded ethyl 6-methyl-1-phenyl-3,4-
disubstituted-4,3a-dihydro-1,2,4-triazolino[4,3-a]pyrimidine-5-carbo-
xylates (43–46)a,b, respectively (Scheme 5).

Reactions of Hydrazonoyl Halides 411
2101
SCHEME 4
Structures of 43–46 were elucidated on the basis of elemental anal-
1
ysis and spectral data. Thus, the H NMR spectrum of 43a showed
signals at δ = 1.20 (t, 3H), 1.35 (t, 3H), 2.53 (s, 3H), 4.09 (q, 2H), 4.41
(q, 2H), 6.83 (s, 1H), 7.12–7.55 (m, 7H), 8.17–8.21 (d, 2H), and its 13C
NMR spectrum shown in Scheme 5.
In the light of the foregoing results, the mechanism outlined in
Scheme 5 seems to be the most plausible pathway for the formation

2102
A. O. Abdelhamid et al.
SCHEME 5
of 43–46(a,b) from the reaction of the appropriate 7a–10a with the
appropriate 39a,b. The reaction involves initial formation of thiohy-
drazonates (40), which undergoes intermolecular cyclization as soon as
it is formed to give the spiro intermediate (41). Ring chain tautomerism
of spiro intermediate (41) leads to the end products 43–46 via the elim-
ination of hydrogen sulfide.
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. Mass spectra were recorded on a GC-MS

Reactions of Hydrazonoyl Halides 411
2103
QP1000 EX Shimadzu. Elemental analyses were carried out at the
Microanalytical Center of the Cairo University, Egypt. Compounds
2c,10,11 3a,b,13,14 4a,12 and (6–13)a–c15−22 were prepared as previously
reported.
3-Methyl-1-substituted 4-[(Substituted Amino)thioxomethyl]-
2-pyrazolin-5-ones 2a–d
Method A
An equimolar amount of the appropriate 1a and 1b, the appropriate
methyl isothiocyanate, and phenyl isothiocyanate and potassium hy-
droxide (5 mmol each) in dry dimethylformamide (15 mL) were stirred
for 6 h at room temperature. The reaction mixture was diluted with
water (50 mL) and then acidified with dilute hydrochloric acid. The re-
sulting solid was collected and crystallized to give 2a–d, respectively,
as yellow crystals (Tables I and II).
Method B
A mixture of the appropriate 3a, 3b and aniline (5 mmol each) in
ethanol (20 mL) was boiled under reflux for 3 h. The resulting solid was
collected and crystallized from ethanol to give identical products with
the corresponding 2a and 2b.
3-Methyl-4-[methylthio(arylamino)methyl-1-phenyl-
2-pyrazolin-5-ones 4a–c
Method A
A mixture of 4-(dimethylthiomethylene)-3-methyl-1-phenyl-2-pyra-
zolin-5-one (5) (2.78 g, 5 mmol) and the appropriate amine (aniline, p-
topluidine, or benzylamine) (5 mmol) in ethanol (20 mL) was refluxed
for 3 h. The resulting solid was collected and crystallized from ethanol
to give 4a–c, respectively (Tables I and II).
Method B
A mixture of equimolar amounts of 2b and potassium hydroxide
(5 mmol each) in N,N-dimethylformamide (15 mL) was stirred for
2 h. Iodomethane (0.71 g (0.32 mL), 5 mmol) was added to the above
reaction mixture with stirring for 2 h and then diluted with wa-
ter (50 mL). The resulting solid was collected and crystallized to af-
ford a product identical in all respects (mp., mixed mp., and spectra)
with 4a.

2104
A. O. Abdelhamid et al.
TABLE I Characterization Data of the Newly Synthesized
Compounds
Calcd./Found %
Comp.
no.
Mp. ◦
solvent
C
Color
yield %
Mol. formula
(Mol. Wt.)
C
H
N
S
2a
2b
215–7
EtOH
203–205
EtOH
223–5
EtOH
152–4
EtOH
99–101
EtOH
252–5
AcOH
231–4
AcOH
284–7
AcOH
249–1
AcOH
237–9
AcOH
247–50
AcOH
281–3
AcOH
257–60
AcOH
289–91
AcOH
259–62
AcOH
270–72
AcOH
280–3
AcOH
280–2
AcOH
172–175
AcOH
>300
Yellow
65
Yellow
70
Yellow
65
Yellow
82
Yellow
85
Yellow
88
Yellow
90
Yellow
90
Yellow
85
Yellow
89
Yellow
87
Yellow
90
Yellow
85
Yellow
85
Yellow
85
Yellow
90
C6H9N3O S
171.22
42.09
42.20
58.28
58.40
56.63
56.80
67.63
67.50
67.63
67.80
53.16
53.00
54.53
54.70
47.94
47.70
54.53
54.70
55.80
55.90
49.39
49.50
55.99
56.10
57.31
57.10
50.23
50.10
62.97
62.80
63.81
63.90
57.50
57.30
60.46
60.30
55.41
55.30
55.42
55.20
56.53
56.30
50.68
50.80
5.30
5.10
5.30
5.50
4.75
4.50
5.68
5.80
5.68
5.80
3.82
3.90
4.27
4.30
3.16
2.90
4.27
4.30
4.68
4.60
3.59
3.70
4.03
4.00
4.49
4.60
3.31
3.30
3.89
3.80
4.28
4.00
3.30
3.10
4.01
3.90
3.43
3.30
3.28
3.10
3.69
3.80
2.75
2.90
24.54
24.30
16.99
17.20
18.01
17.90
12.45
12.50
12.45
12.60
17.71
17.90
16.96
16.80
15.97
15.70
16.96
17.10
16.27
16.40
15.36
15.60
18.65
18.50
17.82
17.90
16.74
16.60
15.46
15.20
14.88
14.90
14.12
14.10
18.56
18.70
17.00
17.20
15.21
15.30
14.65
14.60
13.91
14.10
18.73
18.50
12.97
13.10
13.75
13.90
9.50
9.40
9.50
9.30
10.14
10.30
9.71
9.80
9.14
9.30
9.71
9.60
9.31
9.50
8.79
8.90
10.68
10.80
10.20
10.00
9.58
9.70
8.85
8.60
8.52
8.70
8.08
8.00
8.50
C
12H13N3O S
247.31
2c
C11H11N3O S
233.29
4b
C19H19N3O S
337.44
4c
C19H19N3O S
337.44
17a
17b
17c
18a
18b
18c
19a
19b
19c
20a
20b
20c
21a
21c
22a
22b
22c
C14H12N4O3S
316.33
C
15H14N4O3S
330.36
C14H11Cl N4O3S
350.78
C15H14N4O3S
330.36
C
16H16N4O3S
344.38
C
15H13Cl N4O3S
364.80
C14H12N4O2S
300.33
C15H14N4O2S
314.36
C
14H11Cl N4O2S
334.78
C19H14N4O2S
362.40
C
20H16N4O2S
376.43
Yellow
90
Yellow
85
Yellow
90
Pale red
89
Pale red
85
Pale red
90
C
19H13Cl N4O2S
396.85
C19H15N5O2S
377.42
19H14Cl N5O2S
411.86
17H12N4O2S2
368.43
C18H14N4O2S2
382.46
8.30
7.79
7.90
17.41
17.60
16.77
16.50
15.92
15.70
C
C
AcOH
188–191
AcOH
245–247
AcOH
C
17H11Cl N4O2S2
402.88
(Continued)

Reactions of Hydrazonoyl Halides 411
2105
TABLE I Characterization Data of the Newly Synthesized
Compounds (Continued)
Calcd./Found %
Comp.
no.
Mp. ◦
solvent
C
Color
yield %
Mol. formula
(Mol. Wt.)
C
H
N
S
23a
23b
23c
24a
24b
24c
25a
25b
25c
26a
26b
26c
27a
27b
27c
28a
28b
28c
29a
29b
29c
30a
245–248
AcOH
235–238
AcOH
231–234
AcOH
213–215
AcOH
225–227
AcOH
233–235
AcOH
265–67
AcOH
250–52
AcOH
Pale red
90
Pale red
87
Pale red
80
Pale red
85
Pale red
88
Pale red
90
Yellow
90
Yellow
88
Yellow
85
Yellow
90
Yellow
89
Yellow
87
Yellow
88
Yellow
90
Yellow
85
Yellow
85
C17H12N4O3S
352.36
57.95
58.10
59.01
59.00
52.79
52.90
66.97
66.80
67.59
67.60
61.81
61.90
61.21
61.10
62.05
62.10
56.27
56.40
62.05
62.20
62.84
62.60
57.21
57.10
63.81
63.90
64.60
64.40
58.46
58.60
68.48
68.60
69.01
69.20
63.49
63.60
66.21
66.00
66.79
66.90
61.54
61.70
62.14
62.10
3.43
3.30
3.85
3.70
2.87
2.70
3.91
4.10
4.25
4.40
3.38
3.40
4.11
4.00
4.46
4.60
3.54
3.40
4.46
4.60
4.79
4.90
3.89
4.00
4.28
4.40
4.65
4.50
3.68
3.80
4.14
4.00
4.415
4.40
3.62
3.80
4.22
4.10
4.53
4.40
3.72
3.60
3.63
3.50
15.90
16.10
15.29
15.10
14.48
14.60
13.58
13.70
13.14
13.00
12.54
12.70
14.28
14.30
13.78
13.80
13.12
13.20
13.87
13.80
13.32
13.20
12.71
12.60
14.88
14.70
14.35
14.20
13.46
13.40
12.78
12.90
12.38
12.40
11.85
11.90
15.44
14.30
14.98
15.10
14.35
14.50
12.60
12.50
9.10
8.90
8.75
8.50
8.29
8.40
7.77
7.90
7.52
7.70
7.18
7.00
8.17
8.00
7.98
7.90
7.51
7.70
7.89
7.90
7.63
6.36
7.27
7.30
8.52
8.60
8.21
8.10
7.80
7.90
7.31
7.10
7.09
6.90
6.78
6.90
7.07
6.90
6.89
7.00
6.57
6.60
14.43
14.60
C
18H14N4O3S
366.39
C17H11Cl N4O3S
386.81
C
23H16N4O2S
412.46
C
24H18N4O2S
426.49
C23H15Cl N4O2S
446.91
C20H16N4O3S
392.43
C21H18N4O3S
406.45
254–56
AcOH
C20H15ClN4O3S
426.87
C21H18N4O3S
406.45
266–6811
AcOH
242–44
AcOH
C22H20N4O3S
420.48
250–52
AcOH
C21H17ClN4O3S
440.90
C20H16N4O2S
376.43
280–8211
AcOH
200–203
AcOH
C
21H18N4O2S
390.45
255–57
AcOH
C20H15ClN4O2S
410.87
>30011
AcOH
C25H18N4O2S
438.50
290–91
AcOH
Yellow
87
Yellow
88
Yellow
85
Yellow
90
Yellow
90
Pale red
85
C26H20N4O2S
452.52
C25H17ClN4O2S
472.94
C25H19N5O2S
453.51
280–82
AcOH
>30011
AcOH
260–62
AcOH
290–3
AcOH
>300
C25H21N5O2S
467.54
C25H18Cl N5O2S
487.96
C23H16N4O2S2
AcOH
444.53
(Continued on next page)

2106
A. O. Abdelhamid et al.
TABLE I Characterization Data of the Newly Synthesized
Compounds (Continued)
Calcd./Found %
Comp.
no.
Mp. ◦
solvent
C
Color
yield %
Mol. formula
(Mol. Wt.)
C
H
N
S
30b
30c
31a
31b
31c
32a
32b
32c
35a
35b
35c
36a
36b
36c
37a
37b
37c
38a
38b
38c
39a
39b
>300
AcOH
270–2
AcOH
>300
AcOH
>300
AcOH
>300
AcOH
240–3
AcOH
230–32
AcOH
272–75
AcOH
217–219
EtOH
225–227
EtOH
247–249
EtOH
160–163
EtOH
185–187
EtOH
243–245
EtOH
147–149
EtOH
185–187
EtOH
190–193
EtOH
203–205
EtOH
254–256
EtOH
Pale red
80
Pale red
80
Pale red
85
Pale red
87
Pale red
80
Pale red
85
Pale red
85
Pale red
88
Yellow
70
Yellow
65
Yellow
70
Yellow
68
Yellow
65
Yellow
70
Yellow
65
Yellow
65
C24H18N4O2S2
458.55
62.86
62.60
57.67
57.80
64.47
64.60
65.14
65.00
59.68
59.80
71.29
71.40
71.69
71.50
66.60
66.50
69.66
70.10
70.13
70.00
70.13
70.20
71.71
71.90
72.14
72.20
72.14
72.00
74.83
74.80
75.13
75.30
75.13
75.00
72.64
72.60
72.99
73.10
72.99
72.80
47.33
47.30
57.13
57.00
3.96
4.10
3.16
3.00
3.76
3.50
4.10
3.90
3.27
3.30
4.13
4.12
4.41
4.20
3.66
3.50
4.98
5.00
5.25
5.40
5.25
5.10
4.86
4.60
5.16
5.30
5.16
5.30
4.66
4.50
4.93
5.10
4.93
5.10
4.72
4.50
4.98
4.70
4.98
5.20
4.26
4.10
5.14
4.20
12.22
12.10
11.70
11.90
13.08
12.80
12.66
12.80
12.10
12.20
11.47
11.60
11.15
11.00
10.71
10.80
15.04
14.80
14.60
14.40
14.60
14.50
16.08
15.90
15.58
15.70
15.58
15.70
14.08
13.80
13.69
13.90
13.69
13.60
16.40
16.20
15.96
15.80
15.96
16.10
7.89
13.99
14.10
13.39
13.50
7.48
7.50
7.25
7.40
6.93
7.10
6.56
6.70
6.38
6.50
6.13
6.30
C23H15Cl N4O2S2
478.97
C23H16N4O3S
428.46
C
24H18N4O3S
442.49
C23H15Cl N4O3S
462.90
C29H20N4O2S
488.56
C
30H22N4O2S
502.58
C29H19Cl N4O2S
523.00
C27H23N5O3
465.50
C28H25N5O3
479.53
C28H25N5O3
479.53
C26H21N5O2
435.47
C27H23N5O2
449.50
C27H23N5O2
449.50
8.00
C
C
C
31H23N5O2
497.54
32H25N5O2
511.57
32H25N5O2
511.57
Yellow
70
Yellow
65
Yellow
70
Yellow
70
Yellow
85
White
80
C31H24N6O2
512.56
C32H26N6O2
526.58
C32H26N6O2
526.58
C14H15Br N2O2S
355.25
277–279
EtOH
193–95
EtOH
151–53
EtOH
9.03
9.20
10.89
10.90
7.90
9.52
9.70
C14H15F N2O2S
294.34
(Continued)

Reactions of Hydrazonoyl Halides 411
2107
TABLE I Characterization Data of the Newly Synthesized
Compounds (Continued)
Calcd./Found %
Comp.
no.
Mp. ◦
solvent
C
Color
yield %
Mol. formula
(Mol. Wt.)
C
H
N
S
43a
43b
44a
44b
45a
45b
46a
46b
163–65
EtOH
190–192
EtOH
212–214
EtOH
220–222
EtOH
143–145
EtOH
163–165
EtOH
177–178
EtOH
113–115
EtOH
Yellow
85
Yellow
89
Yellow
88
Yellow
81
Yellow
89
Yellow
90
Yellow
87
Yellow
85
C24H23F N4O4
511.36
56.37
56.10
56.37
56.10
57.39
57.40
65.70
65.60
61.89
61.80
69.70
69.60
60.22
60.10
67.60
67.70
4.53
4.70
4.53
4.70
4.40
4.10
5.03
5.10
4.27
4.00
4.80
4.70
4.33
4.10
4.86
4.60
10.95
11.20
10.95
11.20
11.64
11.80
13.33
13.50
10.31
10.60
11.61
11.50
12.54
12.40
14.08
13.90
C24H23F N4O4
511.36
C23H21Br N4O3
481.34
C23H21F N4O3
420.43
C28H23Br N4O3
543.41
C28H23F N4O3
482.50
C
28H24Br N5O3
558.42
C28H24F N5O3
497.52
2,3-Dihydro-1,3,4-thiadiazoles (17–24)a–c, (25–32)a–c,
5-(3-Methyl-5-oxo-1-phenyl(2-pyrazolin-4-ylidene))-1,4-
disubstituted-1,2,4-triazolines (35–38)a–c
General method. Equimolar ammount of the appropriate hydra-
zonoyl halides (6–13)a–c, the appropriate pyrazoline-5-ones (2, 3)a,b or
4a–c, and triethylamine (5 mmol) in ethanol (20 mL) was stirred at room
temperature (or boiled under reflux) for 2 h. The resulting solid was col-
lected and crystallized to give 2,3-dihydro-1,3,4-thiadiazoles(17–24)a–
c, (25–32)a–c and 5-(3-methyl-5-oxo-1-phenyl(2-pyrazolin-4-ylidene))-
1,4-disubstituted-1,2,4-triazolines (35–38)a–c, respectively (Tables I
and II).
Ethyl 4-Methyl-5-substituted-2-thioxo-1,3,6-trihydropyridine-
5-carboxylates 39a and 39b
A mixture of ethyl acetoacetate (0.1 mol, 13 g), thiourea (0.12 mol, 8.2 g)
and the appropriate aromatic aldehydes (3-bromobenzaldehyde or 4-
florobenzaldehyde) (0.1 mol) in ethanol (30 mL) containing a catalytic
amount of concentrated hydrochloric acid (10 drops) was refluxed for
3 h. The reaction mixture was then allowed to stand at room temper-
ature overnight. The solid precipitate that formed was collected by fil-
tration, washed with ethanol, and crystallized from ethanol to give 39a
and 39b, respectively (Table I).

2108
A. O. Abdelhamid et al.
TABLE II 1H NMR Spectra of Some Selected Synthesized Compounds
Comp. no.
1H NMR (δ)
4c
2.16 (s, 3H), 2.21 (s, 3H), 4.54 (s, 2H), 7.23–7.39 (m, 8H), 7.95–7.99 (d, 2H),
12.92 (s, br., 1H)
17c
18a
18b
1.14 (s, 3H), 3.97 (s, 3H), 7.73–7.87 (m, 4H), 11.29 (s, br., 1H)
1.04 (s, 3H), 1.34 (t, 3H), 4.41 (q, 2H), 7.64–7.80 (m, 5H), 11.26 (s, br., 1H)
0.82 (s, 3H), 1.08 (t, 3H), 2.25 (s, 3H), 4.15 (q, 2H), 7.18–7.23 (d, 2H),
7.36–7.40 (d, 2H), 10.97 (s, br., 1H)
19a
21b
1.21 (s, 3H), 2.54 (s, 3H), 7.08–7.81 (m, 5H), 11.56 (s, br., 1H)
2.35 (s, 3H), 2.55 (s, 3H), 7.11–7.65 (m, 9H), 11.94 (s, br., 1H), 14.75
(s, br., 1H)
22a
25b
1.07 (s, 3H), 7.35–7.37 (m, 1H), 7.68–7.90 (m, 5H), 8.24–8.38 (d, 2H),
11.28 (s, br., 1H)
1.38 (s, 3H), 2.50 (s, 3H), 4.03 (s, 3H), 7.11–7.42 (m, 3H), 7.56 (s, 4H),
7.92–8.02 (d, 2H)
25c
26a
1.39 (s, 3H), 4.01 (s, 3H), 7.15–7.42 (m, 3H), 7.56 (s, 4H), 7.97–8.20 (d, 2H)
1.28 (s, 3H), 1.42 (t, 3H), 4.45 (q, 2H), 7.09–7.42 (m, 4H), 7.59 (s, 4H),
7.99–8.03 (d, 2H)
26c
27a
29b
1.28 (s, 3H), 1.33 (t, 3H), 4.44 (q, 2H), 7.12–7.99 (m, 9H)
1.37 (s, 3H), 2.56 (s, 3H), 7.07–8.02 (m, 10H)
1.31 (s, 3H), 2.50 (s, 3H), 7.12–7.61 (m, 12H), 7.98–8.03 (d, 2H),
8.44 (sb, br., 1H)
30a
1.30 (s, 3H), 6.63 (m, 1H), 7.25–7.44 (m, 5H), 7.66–7.70 (m, 5H), 7.81–7.86
(d, 2H)
36a
36c
38b
43b
2.18 (s, 3H), 2.33 (s, 3H), 7.14–8.03 (m, 15H)
2.13 (s, 6H), 4.62 (s, 2H), 7.22–8.43 (m, 15H)
1.84 (s, 3H), 2.51 (s, 3H), 6.24–8.70 (m, 19H), 11.25 (s, br., 1H)
1.22 (t, 3H), 1.37 (t, 3H), 2.52 (s, 3H), 4.04 (q, 2H), 4.39 (q, 2H),
6.85–6.97 (m, 3H), 7.31–7.47 (m, 5H), 8.17–8.21 (d, 2H)
1.23 (t, 3H), 2.52 (s, 3H), 2.54 (s, 3H), 4.04 (q, 2H), 6.84 (s, 1H),
7.26–7.55 (m, 7H), 8.20 (d, 2H)
1.21 (t, 3H), 2.52 (s, 6H), 4.07 (q, 2H), 6.85–6.96 (m, 3H), 7.34–7.54
(m, 5H), 8.24–8.25 (d, 2H)
1.21 (t, 3H), 2.57 (s, 3H), 4.08 (q, 2H), 6.85–7.01 (m, 3H), 7.34–7.51
(m, 8H), 8.06–8.11 (d, 2H), 8.21–8.26 (d, 2H)
1.24 (t, 3H), 2.57 (s, 3H), 4.07 (q, 2H), 6.99 (s, 1H), 7.06–7.55 (m, 10H),
8.09–8.14 (d, 2H), 8.21–8.25 (d, 2H)
1.23 (t, 3H), 2.55 (s, 3H), 4.07 (q, 2H), 7.01 (s, 1H), 7.11–7.34 (m, 2H),
7.38–7.69 (m, 10H), 8.16–8.53 (d, 2H), 8.45 (s, br., 1H)
1.22 (t, 3H), 2.53 (s, 3H), 4.07 (q, 2H), 6.91–7.34 (m, 3H),
7.42–7.60 (m, 10H), 8.16–8.20 (d, 2H), 8.47 (s, br., 1H)
44a
44b
45a
45b
46a
46b
Ethyl 6-Methyl-1-phenyl-3,4-disubstituted-4,3a-dihydro-1,2,4-
triazolino[4,3-a]pyrimidine-5-carboxylates (43–46)a,b
An equimolar amount of each of the appropriate hydrazonoyl halides
(7–10)a and the appropriate pyrimidine-2-thione derivatives 39a,b
and triethylamie (5 mmol) in chloroform (20 mL) was boiled under

Reactions of Hydrazonoyl Halides 411
2109
reflux for 10 h. Chloroform was evaporated under reduced pressure
and the residue solid was crystallized from ethanol to give triazlino[4,3-
a]pyrimidines (43–46)a,b (Tables I and II).
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