Reactions with hydrazonoyl halides 611: Synthesis of 2,3-dihydro-1,3,4-thiadiazoles

Article abstract of DOI:10.1080/10426500801968185

2-[1,2-Diaza-3-(2,3-dimethyl-5-oxo-1-phenyl(3-pyrazolin-4-yl)) prop-2-enylidene]-3-phenyl-5-substituted 1,3,4-thiadiazolines and 2-{[4-(2,3-dimethyl-5-oxo-1-phenyl(3-pyrazolin-4-yl))(1,3-thiazol-2-yl)] cyanomethylene}-3-phenyl-5-substitu- ted 1,3,4-thiadi

Full text of DOI:10.1080/10426500801968185

This article was downloaded by: [University of Connecticut]
On: 14 July 2013, At: 12:16
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954
Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH,
UK
Phosphorus, Sulfur, and Silicon
and the Related Elements
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/gpss20
Reactions with Hydrazonoyl
Halides 611: Synthesis of 2,3-
Dihydro-1,3,4-Thiadiazoles
Abdou O. Abdelhamid a & Mamdouh A. M. Afifi a
a Department of Chemistry, Faculty of Science, Cairo
University, Giza, Egypt
Published online: 10 Oct 2008.
To cite this article: Abdou O. Abdelhamid & Mamdouh A. M. Afifi (2008) Reactions
with Hydrazonoyl Halides 611: Synthesis of 2,3-Dihydro-1,3,4-Thiadiazoles,
Phosphorus, Sulfur, and Silicon and the Related Elements, 183:11, 2703-2713
To link to this article: http://dx.doi.org/10.1080/10426500801968185
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the
information (the “Content”) contained in the publications on our platform.
However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness,
or suitability for any purpose of the Content. Any opinions and views
expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the
Content should not be relied upon and should be independently verified with
primary sources of information. Taylor and Francis shall not be liable for any
losses, actions, claims, proceedings, demands, costs, expenses, damages,
and other liabilities whatsoever or howsoever caused arising directly or
indirectly in connection with, in relation to or arising out of the use of the
Content.

This article may be used for research, teaching, and private study purposes.
Any substantial or systematic reproduction, redistribution, reselling, loan,
sub-licensing, systematic supply, or distribution in any form to anyone is
expressly forbidden. Terms & Conditions of access and use can be found at
http://www.tandfonline.com/page/terms-and-conditions

Phosphorus, Sulfur, and Silicon, 183:2703–2713, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500801968185
Reactions with Hydrazonoyl Halides 611: Synthesis
of 2,3-Dihydro-1,3,4-Thiadiazoles
Abdou O. Abdelhamid and Mamdouh A. M. Afifi
Department of Chemistry, Faculty of Science, Cairo University,
Giza, Egypt
2-[1,2-Diaza-3-(2,3-dimethyl-5-oxo-1-phenyl(3-pyrazolin-4-yl))prop-2-enylidene]-
3-phenyl-5- substituted 1,3,4-thiadiazolines and 2-{[4-(2,3-dimethyl-5-oxo-1-
phenyl(3-pyrazolin-4-yl))(1,3-thiazol-2-yl)]cyanomethylene}-3-phenyl-5-substitu-
ted 1,3,4-thiadiazolines were synthesized from hydrazonoyl halides and 4-{-2-aza-
2-[(methylthiothioxomethyl)amino]vinyl}-2,3-dimethyl-1-phenyl-3-pyrazoin-5-one
and
2-[4-(2,3-dimethyl-5-oxo-1-phenyl-3-pyrazolin-4-yl)-1,3-thiazol-2-yl]ethane-
nitrile, respectively. All synthesize compounds were elucidated by elemental
analysis, spectra, and alternative synthesis routes, whenever possible.
Keywords 2,3-Dihydro-1,3,4-thiadiazoles; alkyl carbodithiates; antipyrine; hydrazonoyl
halides; thioamides
INTRODUCTION
Hydrazonoyl halides have been widely used for the synthesis of
heterocyclic compounds.1−9 Also, 1,3,4-thiadiazoles are active in many
biological systems such as antitumor,10 hypoglycemic properties,11
antihistamine,12 and anticholinergic.13 We report herein the re-
activity of hydrazonoyl halides towards 4-{-2-aza-2-[(methylth-
iothioxomethyl)amino]vinyl}-2,3-dimethyl-1-phenyl-3-pyrazoin-5-one
and 2-[4-(2,3-dimethyl-5-oxo-1-phenyl-3-pyrazolin-4-yl)-1,3-thiazol-2-
yl]ethanenitrile.
RESULTS AND DISCUSSION
Treatment of the appropriate alkyl hydrazinecarbodithioate14 (2a,b)
with 2,3-dimethyl-5-oxo-1-phenyl-3-pyrazoline-4-carbaldehyde15 (1)
Received 2 December 2007; accepted 4 February 2008.
Address correspondence to Abdou O. Abdelhamid, Department of Chemistry, Faculty
of Science, Cairo University, Giza 12613, Egypt. E-mail: abdelhamid45@gmail.com
2703

2704
A. O. Abdelhamid and M. A. M. Afifi
in 2-propanol afforded 4-{-2-aza-2-[(methylthiothioxomethyl)amino]
vinyl}-2,3-dimethyl-1-phenyl-3-pyrazoin-5-one (3a) and 4-{-2-aza-2-
[(phenylmethylthio)thioxomethyl]amino}vinyl}-2,3-dimethyl-1-phenyl
1
-3-pyrazoin-5-one (3b). The H NMR spectrum of 3a showed signals
at δ = 2.44 (s, 3H, CH3), 2.55 (s, 3H), 2.62 (s, 3H), 7.56−8.38 (m, 7H)
and 12.52 (s, br., 1H). Compound 3a reacted with the appropriate
hydrazonoyl halides 4a in ethanolic triethylamine at room temperature
to give ethyl 2-[1,2-diaza-3-(2,3-dimethyl-5-oxo-1-phenyl(3-pyrazolin-
4-yl))prop-2-enylidene]-3-phenyl-1,3,4-thiadiazoline-5-carboxylate 8a
(Scheme 1). Structure 8 was confirmed by elemental analysis, spectral
data and an alternate synthetic route. Thus, 1H NMR spectrum of
8a showed signals at δ = 1.42 (t, 3H, CH2 CH3), 2.67 (s, 3H, CH3),
3.25 (s, 3H, CH3) 4.44 (q, 2H, CH2CH3), 7.23−7.47 (m, 8H, ArH’s),
SCHEME 1

Synthesis of 2,3-Dihydro-1,3,4-Thiadiazoles
2705
7.85 (d, 2H, J = 5 Hz, and 8.43 (s, 1H, vinyl CH=N). Its IR revealed
bands at 1708, 1668 (CO’s), and 1506 (C=C). Also, treatment of ethyl
2-hydrazino-3-phenyl-2,3-dihydro-1,3,4-thiadiazole-5-carboxylate16
(9) with 1 in 2-propanol afforded a product identical to 8a. In the
light of the forgoing results, the mechanism outlined in Scheme 1
seems to be the most plausible pathway for the formation of 8 from
the reaction between 3 and 4. The reaction involves initial formation
of thiohydrazonate 6, which undergoes intramolecular cyclization as
soon as it is formed to yield the intermediate 7 or via 1,3-dipolar
cycloaddition of nitrilimine 5, which prepared in situ from 4 with
triethylamine, to C S double bond of 3 to give the intermediate 7.
Intermediate 7 is converted to the final product 8 via elimination of
methyl mercaptan.
Analogously, treatment of the appropriate 4b−l with each of methyl
hydrazinecarbodithioate 3a or benzyl hydrazinecarbodithioate 3b in
ethanolic triethylamine at room temperature, afforded the correspond-
ing 2,3-dihydro-1,3,4-thiadiazoles 8b−l, respectively.
Treatment of 4-(2-chloroacetyl)-2,3-dimethyl-1-phenyl-3-pyrazolin-
5-one (10) with cyanothioacetamide (11) in ethanol afforded
2-[4-(2,3-dimethyl-5-oxo-1-phenyl-3-pyrazolin-4-yl)-1,3-thiazol-2-
yl]ethanenitrile (12). The structure of the product was supported by its
elemental analysis and spectral data. Compound 12 was reacted with
phenyl isothiocyanate in N, N-dimethylformamide containing potas-
sium hydroxide to give 2-[4-(2,3-dimethyl-5-oxo-1-phenyl(3-pyrazolin-
4-yl))(1,3-thiazol-2-yl)]-3-(phenylamino)-3-thioxopropanenitrile
(13)
(Scheme 2). Thus, the reaction of 13 with C-ethoxycarbonyl-N-
phenylhydrazonoyl chloride 4a in ethanolic triethylamine gave the
ethyl 2-[4-(2,3-dimethyl-5-oxo-1-phenyl(3-pyrazolin-4-yl))(1,3-thiazol-
2-yl)]cyanomethylene-3-phenyl-1,3,4-thiadiazoline-5-carboxylate
(16a), as evidenced from its elemental analysis and spectral data, in
good yield (Scheme 2).
Structure 16 was confirmed by elemental analysis, spectral data, and
1
an alternate synthetic route. Thus, H NMR spectrum of 16a showed
signals at δ = 1.46 (t, 3H, CH3CH2), 2.90 (s, 3H, CH3), 3.23 (s, 3H,
CH3), 4.48 (q, 2H, CH2CH3), 7.25-7.58 (m, 10H, ArH’s) and 8.06 (s, 1H,
thiazole H-5). Its IR revealed bands at 2191 (CN), 1705, 1691 (CO’s), and
1595 (C=C). Meanwhile, the product seemed to be one of two isomeric
structures 16 and 17. By M.O. calculation using Hyper-Chem and MBI3
method15 showed for structure 16 the binding energy = −6583 K.Cal /
mol and heat of formation = 166.51 K.Cal/mol, whereas the structure
17 the binding energy = -6516 K.Cal / mol and heat of formation =
233.60 K.Cal /mol. From these results, the isomeric 16 more stable
than isomeric 17.

2706
A. O. Abdelhamid and M. A. M. Afifi
SCHEME 2
The formation of product 16 can be explained via elimination of ani-
line from the cycloadduct of nitrile imide 5 (which was generated in situ
by treatment of hydrazonoyl chloride 4 with base) to CS double bond
of thioanilide 13 or by stepwise path involving substitution to give a
cyclic hydrazone 14, which easy converted into cyclic intermediate 15.
The latter gave16 via the elimination of aniline (Scheme 3).
An unequivocal support for structure 16a, came from the reac-
tion of the appropriate C-ethoxycarbonyl-N-phenylhydrazonoyl chlo-
ride 4a with 2-[4—(2,3-dimethyl-5-oxo-1-phenyl(3-pyrazolin-4-yl))(1,3-
thiazol-2-yl)]-3-methylthio-3-sulfanylprop-2-enenitrile (18), which was
prepared from 12 with carbon disulfide in N, N-dimethylformamide
containing potassium hydroxide followed by addition of iodomethane,
in presence of triethylamine gave product identical in all aspects (m.p.,

Synthesis of 2,3-Dihydro-1,3,4-Thiadiazoles
2707
SCHEME 3
mixed m.p. and spectra) with 16a via elimination of methyl mercaptan
(Scheme 3).
EXPERIMENTAL
All melting points were determined on an electrothermal melting point
Gallen-Kamp apparatus and are uncorrected. IR (cm−1) spectra were
recorded on KBr disk on a FTIR-8201 PC Shimadzu spectrophotome-
1
ter. HNMR spectra were recorded in CDCl3 or (CD3)2SO on Gemini
200 MHz and Varian 300 MHz spectrometers, using TMS as internal
reference. and chemical shifts are express as δ ppm unit. Elemental
analysis was performed at the Microanalytical Center in Cairo Univer-
sity. Hydrazonoyl halides 4a−l were prepared as previously reported
in literature.17−21
Synthesis of 4-{-2-Aza-2-[(methylthiothioxomethyl)amino]
vinyl}-2,3-dimethyl-1-phenyl-3-pyrazoin-5-one (3a) and 4-{-2-
Aza-2-[(phenylmethylthio)thioxomethyl]amino}vinyl}-2,3-
dimethyl-1-phenyl-3-pyrazoin-5-one (3b)— General
Procedure
A mixture of the appropriate alkyl hydrazinecarbodithioate14 (2a,b)
with 2,3-dimethyl-5-oxo-1-phenyl-3-pyrazoline-4-carbaldehyde (1) (10
mmoles) in 1-propanol (20 mL) was stirred at room temperature for 2
h. The solid, so formed, was collected and recrystallized from ethanol
to give 3a and 3b, respectively (Tables I and II).

2708
A. O. Abdelhamid and M. A. M. Afifi
TABLE I Characterization Data of the Newly Synthesized
Compounds
% Analyses, calcd./found
Compd.
no.
M.p.,◦C
solvent
Yielda
Color
%
Mol. formula
m.wt.
C
H
N
S
3a
3b
8a
8b
8c
240–242
DMF
228–232
AcOH
244–246
EtOH
288–290
EtOH
332–335
AcOH
272–274
AcOH
218–220
EtOH
240–242
AcOH
235–237
AcOH
215–217
EtOH
248–252
EtOH
288–290
DMF
280–282
AcOH
262–264
AcOH
180–182
EtOH
247–249
DMF
80
Yellow
85
Yellow
68
Yellow
69
Orange
64
Yellow
68
Yellow
65
Yellow
66
Yellow
67
Yellow
69
Yellow
65
Orange
63
Yellow
69
Yellow
62
Yellow
78
Buff
70
Buff
60
C14H16N4OS2
320.44
52.48 5.03
52.53 4.92
60.58 5.08
60.37 4.89
59.73 4.79
59.62 4.58
61.10 4.66
61.20 4.85
63.64 4.55
63.54 4.65
65.57 4.48
65.75 4.68
68.37 4.44
68.45 4.24
59.98 4.03
59.85 3.92
61.97 4.16
61.88 4.15
60.49 5.08
60.57 5.11
61.87 4.97
61.74 4.79
64.23 4.81
64.33 4.92
66.12 4.76
66.00 4.67
66.93 4.75
66.88 4.65
61.92 4.55
61.82 4.62
62.00 4.30
62.12 4.21
59.76 4.09
59.67 3.89
60.92 3.93
60.85 3.75
63.14 3.93
63.00 3.85
64.79 3.86
64.97 3.68
67.29 3.87
67.35 3.78
59.98 3.47
59.89 3.64
17.48 20.01
17.56 19.95
14.13 16.17
14.28 16.00
C
20H20N4OS2
396.54
C23H22N6O3S
462.58
18.17
18.27
19.43
19.34
19.24
19.15
16.99
17.22
15.43
15.33
6.93
7.11
7.41
7.28
6.29
6.34
6.48
6.45
5.89
5.98
C
22H20N6O2S
432.51
C
27H23N7O2S
509.59
8d
8e
C27H22N6O2S
494.58
C
31H24N6O2S
544.64
8f
C25H20N6O2S2
500.61
16.79 12.81
16.97 12.68
8g
8h
8i
C
C
C
C
25H20N6O3S
484.54
24H24N6O3S
476.56
23H22N6O2S
446.53
28H25N7O2S
523.62
17.34
17.43
17.63
17.68
18.82
18.78
18.72
18.67
16.52
16.45
18.01
17.89
6.62
6.58
6.73
6.58
7.18
7.00
6.12
6.34
6.30
6.15
6.87
6.78
8j
8k
8l
C28H24N6O2S
508.61
C
26H22N6OS
466.57
12
C
16H14N4OS
310.38
18.05 10.33
17.89 10.24
15.72 14.39
15.60 14.21
15.49 11.82
15.35 11.72
16.39 12.51
16.54 12.65
16.63 10.87
16.57 10.78
14.62 11.06
14.57 11.00
13.45 10.26
13.54 10.32
14.47 16.56
14.52 16.40
13
C
23H19N5OS2
445.57
16a
16b
16c
16d
16e
16f
318–321
AcOH
326–329
AcOH
351–354
AcOH
301–303
AcOH
319–321
AcOH
324–326
AcOH
C
27H22N6O3S2
542.64
Yellow
61
Orange
59
Orange
58
Orange
56
C26H20N6O2S2
512.62
C
C
C
C
31H23N7O2S2
589.70
31H22N6O2S2
574.69
35H24N6O2S2
624.75
29H20N6O2S3
580.71
Orange
53
Orange
(Continued on next page)

Synthesis of 2,3-Dihydro-1,3,4-Thiadiazoles
2709
TABLE I Characterization Data of the Newly Synthesized
Compounds (Continued)
% Analyses, calcd./found
Compd.
no.
M.p.,◦C
solvent
Yielda
Color
%
Mol. formula
m.wt.
C
H
N
S
16g
16h
18
332–334
AcOH
288–289
AcOH
345–347
DMF
55
Orange
60
Orange
62
C29H20N6O3S2
564.65
61.69 3.57
61.54 3.75
61.58 4.21
61.85 4.32
53.98 4.03
53.78 4.10
14.88 11.36
14.77 11.21
15.96 12.18
15.72 12.00
13.99 24.02
14.12 23.82
C
27H22N6O2S2
526.64
C18H16N4OS3
400.55
Orange
Synthesis of 2-[1,2-Diaza-3-(2,3-dimethyl-5-oxo-1-phenyl(3-
pyrazolin-4-yl))prop-2-enylidene]-3-phenyl-5-substituted
1,3,4-thiadiazoline 8a-l
Method A
Triethylamine (1.5 ml, 10 mmol) was added to a stirred solution of
the appropriate of alkyl carbodithioates 3a or 3b (10 mmol) and the
appropriate hydrazonyl halides 4a−l (10 mmol) in ethanol (20 ml)
at room temperature. The reaction mixture was stirred for 2 h, the
resulting solid was collected and recrystallized from ethanol to give
2-[1,2-diaza-3-(2,3-dimethyl-5-oxo-1-phenyl(3-pyrazolin-4-yl))prop-2-
enylidene]-3-phenyl–5-substituted 1,3,4-thiadiazolines 8a−l (Tables I
and II).
Method B
Triethylamine (1.5 ml, 10 mmol) was added to a stirred so-
lution of ethyl 2-hydrazino-3-phenyl-2,3-dihydro-1,3,4-thiadiazole-5-
carboxylate (2.63 g, 10 mmol) and the 4-formylantipyrine (1) (2.16 g, 10
mmol) in ethanol (20 ml) at room temperature. The reaction mixture
was stirred for 2 h; the resulting solid was collected and recrystallized
from ethanol to give the products identical in all aspects (m.p., mixed
m.p., and spectra) with obtained from Method A.
Synthesis of 2-[4-(2,3-Dimethyl-5-oxo-1-phenyl-3-pyrazolin-4-
yl)-1,3-thiazol-2-yl]ethanenitrile (12)
A mixture of 10 (2.64 g, 10 mmol) and cyanothioacetamide 11 (1g, 10
mmol) was heated under reflux in ethanol (20 mL methanol) for 2 h. The
reaction mixture was cooled and stirred at room temperature over 1 h
and a few drops of ammonium hydroxide were added. The precipitate

2710
A. O. Abdelhamid and M. A. M. Afifi
TABLE II Spectral Data of Some Newly Synthesized Compounds
Compound No.
Spectral data
3b
1H NMR: 2.67 (s, 3H, CH3), 3.25 (s, 3H, CH3), 4.14 (s, 2H, SCH2),
7.23–7.85 (m, 10 H, ArH’s), 8.43 (s, 1H, vinyl CH N), and 11.62 (s,
1H, NH).
8b
8c
1H NMR: 2.21 (s, 3H, CH3), 2.67 (s, 3H, CH3), 3.25 (s, 3H, CH3),
7.23–7.47 (m, 8H, ArH’s), 7.85 (d, 2H, J = 5 Hz), and 8.43 (s, 1H,
vinyl CH N).
IR: 1668 (CO’s) and 1506 (C C).
1H NMR: 2.67 (s, 3H, CH3), 3.25 (s, 3H, CH3), 7.23–7.47 (m, 13H,
ArH’s), 7.85 (d, 2H, J = 5 Hz), 8.43 (s, 1H, vinyl CH N), and 8.68 (s,
br., 1H, NH).
IR: 1668 (CO’s) and 1506 (C C).
8d
8e
8f
1H NMR: 2.67 (s, 3H, CH3), 3.25 (s, 3H, CH3), 7.23–7.47 (m, 13H,
ArH’s), 7.85 (d, 2H, J = 5 Hz), and 8.43 (s, 1H, vinyl CH N).
IR: 1668 (CO’s) and 1506 (C C).
1H NMR: 2.67 (s, 3H, CH3), 3.25 (s, 3H, CH3), 7.23–7.87 (m, 17H,
ArH’s), and 8.43 (s, 1H, vinyl CH N). IR:
1668 (CO’s) and 1506 (C C).
1H NMR: 2.67 (s, 3H, CH3), 3.25 (s, 3H, CH3), 7.23–7.67 (m, 13H,
ArH’s), and 8.43 (s, 1H, vinyl CH N). IR:
1668 (CO’s) and 1506 (C C).
8g
8h
1H NMR: 2.67 (s, 3H, CH3), 3.25 (s, 3H, CH3), 6.68–7.57 (m, 13H,
ArH’s), and 8.43 (s, 1H, vinyl CH N). IR:
1668 (CO’s) and 1506 (C C).
1H NMR: 1.42 (t, 3H, CH2 CH3), 2.42 (s, 3H, CH3), 2.67 (s, 3H, CH3),
3.25 (s, 3H, CH3), 4.44 (q, 2H, CH2CH3), 7.23–7.58 (m, 9H, ArH’s),
and 8.43 (s, 1H, vinyl CH N).
IR: 1708, 1668 (CO’s) and 1506 (C C).
8i
8j
1H NMR: 2.21 (s, 3H, CH3), 2.41 (s, 3H, CH3), 2.67 (s, 3H, CH3), 3.25
(s, 3H, CH3), 7.23–7.67 (m, 9H, ArH’s), and 8.43 (s, 1H, vinyl CH N).
IR: 1668 (CO’s) and 1506 (C C).
1H NMR: 2.40 (s 3H, CH3), 2.67 (s, 3H, CH3), 3.25 (s, 3H, CH3),
7.23–7.87 (m, 14H, ArH’s), 8.43 (s, 1H, vinyl CH N), and 8.68 (s, br.,
1H, NH).
IR: 1668 (CO’s) and 1506 (C C).
8k
8l
1H NMR: 2.41 (s, 3H, CH3), 2.67 (s, 3H, CH3), 3.25 (s, 3H, CH3),
7.23–7.67 (m, 14H, ArH’s), and 8.43 (s, 1H, vinyl CH N). IR: 1668
(CO’s) and 1506 (C C).
1H NMR: 2.67 (s, 3H, CH3), 3.25 (s, 3H, CH3), 7.23–7.47 (m, 15H,
ArH’s), and 8.43 (s, 1H, vinyl CH N).
IR: 1668 (CO’s) and 1506 (C C).
12
13
1H NMR: 2.76 (s, 3H, CH3), 3.20 (s, 3H, CH3), 4.14 (s, 2H, CH2),
7.26–7.52 (m, 5H, ArH’s), and 8.16 (s, 1H, thiazole H-5).
IR: 3095 (CH), 2191 (CN), 1643 (CO0, 1614 (C N).
1H NMR: 2.76 (s, 3H, CH3), 3.20 (s, 3H, CH3), 7.26–7.52 (m, 10H,
ArH’s), 8.16 (s, 1H, thiazole H-5), 9.12 (s, br., 1H, NH), and 12.13 (s,
1H, SH).
(Continued on next page)

Synthesis of 2,3-Dihydro-1,3,4-Thiadiazoles
2711
TABLE II Spectral Data of Some Newly Synthesized Compounds
(Continued)
Compound
No.
Spectral data
16a
1H NMR: 1.46 (t, 3H, CH3CH2), 2.90 (s, 3H, CH3), 3.23 (s, 3H, CH3), 4.48
(q, 2H, CH2CH3), 7.25–7.58 (m, 10H, ArH’s), and 8.06 (s, 1H, thiazole
H-5).
IR: 2191 (CN), 1705, 1691 (CO), and 1595 (C C)
16b
16c
16d
16e
16f
16g
16h
18
1H NMR: 2.67 (s, 3H, CH3), 2.94 (s, 3H, CH3), 3.27 (s, 3H, CH3), 7.29–7.68
(m, 10H, ArH’s), and 8.09 (s, 1H, thiazole H-5).
IR : 2191 (CN), 1690, 1680 (CO), and 1589 (C C)
1H NMR: 2.94 (s, 3H, CH3), 3.22 (s, 3H, CH3), 7.19—7.65 (m, 15H, ArH’s),
8.04 (s, 1H, thiazole H-5), and 8.48 (s, 1H, NH).
IR: 3354 (NH), 2190 (CN), 1667, (CO), 1643, 1616 (C N), and 1600 (C C).
1H NMR: 2.98 (s, 3H, CH3), 3.27 (s, 3H, CH3), 7.25–7.64 (m, 13H, ArH’s),
8.09 (s, 1H, thiazole H-5), and 8.31 (d, J = 8Hz, 2H, ArH’s).
IR: 2189 (CN), 1670, (CO), 1633, 1622 (C N), and 1593 (C C).
1H NMR: 2.88 (s, 3H, CH3), 3.28 (s, 3H, CH3), 7.25–7.98 (m, 16H, ArH’s),
8.01 (s, 1H, thiazole H-5), and 9.00 (s, 1H, ArH’s).
IR: 2189 (CN), 11743, 1651 (CO), 1620, 1622 (C N), and 1593 (C C).
1H NMR: 2.96 (s, 3H, CH3), 3.26 (s, 3H, CH3), 7.17–7.81 (m, 12H, ArH’s),
8.09 (s, 1H, thiazole H-5), and 8.39 (s, 1H, ArH).
IR: 2191 (CN), 1705, 1658, (CO), 1604 (C N).
1H NMR: 2.94 (s, 3H, CH3), 3.25 (s, 3H, CH3), 6.59 (m, 1H), 7.25–7.84 (m,
12H, ArH’s), and 8.09 (s, 1H, thiazole H-5).
IR: 2191 (CN), 1743, 1651 (CO).
1H NMR: 2.49 (s, 3H, CH3), 2.62 (s, 3H, CH3), 2.90 (s, 3H, CH3), 3.23 (s,
3H, CH3), 7.25–7.48 (m, 9H, ArH’s), and 8.05 (s, 1H, thiazole H-5).
IR: 2185 (CN), 1691, 1660 (CO).
1H NMR: 2.49 (s, 3H, CH3), 2.25 (s, 3H, CH3), 2.62 (s, 3H, CH3), 7.25–7.45
(m, 5H, ArH’s), and 8.05 (s, 1H, thiazole H-5), 12.42 (s, 1H, SH).
was filtered, washed with water, and recrystallized from methanol to
give 12 (Tables I and II).
Synthesis of 2-[4-(2,3-Dimethyl-5-oxo-1-phenyl(3-pyrazolin-4-
yl))(1,3-thiazol-2-yl)]-3-(phenylamino)-3-thioxopropanenitrile
(13)
An equimolar amounts of 2-[4-(2,3-dimethyl-5-oxo-1-phenyl-3-
pyrazolin-4-yl)-1,3-thiazol-2-yl]ethanenitrile (12) and phenyl isothio-
cyanate, potassium hydroxide (10 mmol) in N, N-dimethylformamide
(25 mL) was stirred at room temperature for 6 h. Hydrochloric acid
(2 mL, 3 M) was added; then the resulting solid was collected and
recrystallized from ethanol to give (13) (Tables I and II).

2712
A. O. Abdelhamid and M. A. M. Afifi
Synthesis of 2-{[4-(2,3-Dimethyl-5-oxo-1-phenyl(3-pyrazolin-4-
yl))(1,3-thiazol-2-yl)]cyanomethylene}-3-phenyl-5-substituted
1,3,4-thiadiazoline 16a-h
Method A
A mixture of 2-[4-(2,3-dimethyl-5-oxo-1-phenyl-3-pyrazolin-4-yl)-1,3-
thiazol-2-yl]ethanenitrile (12) (3.10 g, 10 mmol), potassium hydroxide
(0.56 g, 10 mmol) and phenyl isothiocyanate (1.35 g, 10 mmol) in dry
N, N-dimethylformamide (10 ml) was stirred for 6 h; then the appropri-
ate hydrazonoyl halides 4a-e (10 mmol) were added and stirring was
continued for 2 h. The reaction mixture was left overnight and diluted
with water (10 mL). The solid was collected by filtration, washed with
water, dried, and crystallized from acetic acid to give 16a−h.
Method B
A mixture of 12 (3.10 g, 10 mmol), carbon disulfide (0.7 g, 10 mmol)
and potassium hydroxide (0.56 g, 10 mmol) in N, N-dimethylformamide
(15 mL) was stirred at room temperature for 1 h. Iodomethane (1.4 g,
0.62 mL, 10 mmol) was added to the mixture. The reaction mixture was
stirred for 2 h. The appropriate of hydrazonyl halides 4a−e (10 mmol)
and triethylamine (1.5 mL, 10 mmol) were added to the above mixture,
and then the reaction mixture was stirred for 2 h. The resulting solid
was collected and crystallized to give products that were identical in
all respects that (m.p., mixed m.p. and spectra) with 16a−e that were
obtained from Method A.
Synthesis of 2-[4—(2,3-Dimethyl-5-oxo-1-phenyl(3-pyrazolin-
4-yl))(1,3-thiazol-2-yl)]-3-methylthio-3-sulfanylprop-2-
enenitrile (18).
An equimolar amounts of 2-[4-(2,3-dimethyl-5-oxo-1-phenyl-3-
pyrazolin-4-yl)-1,3-thiazol-2-yl]ethanenitrile (12) (3.10 g, 10 mmol),
carbon disulfide (0.7 g, 10 mmol) and potassium hydroxide (0.65 g,
10 mmol) in N, N-dimethylformamide (25 mL) was stirred at room
temperature for 6 h. Iodomethane (0.6 mL (10 mmol) was added then
the resulting solid was collected and recrystallized from ethanol to give
(18) (Tables I and II).
REFERENCES
[1] Part 60: A. O. Abdelhamid, Z. M. Ismail, and A. Abdel-Aziem, J. Chem. Res., 10, 609
(2007).
[2] A. Padwa, Angew. Chem. Int. Ed. Engl., 15, 123 (1976).

Synthesis of 2,3-Dihydro-1,3,4-Thiadiazoles
2713
[3] R. Huisgen, R. Sustmann, and G. Wallbillich, Chem. Ber., 100, 1786 (1976).
[4] A. O. Abdelhamid and F. A. Attaby, J. Heterocyclic Chem., 28, 41 (1991).
[5] A. O. Abdelhamid, M. M. M. Sallam, and S. A. Amer, Heteroatom Chem, 12, 468
(2001).
[6] A. O. Abdelhamid, H. F. Zohdi, and N. A. Ali, Molecules, 5, 961 (2001).
[7] A. O. Abdelhamid, N. M. Rateb, and K. M. Dawood, Phosphorus, Sulfur, Silicon, and
Relat. Elem., 167, 251 (2000).
[8] H. F. Zohdi, N. M. Rateb, M. M. M. Sallam, and A. O. Abdelhamid, J. Chem. Res.
(S), 742; J. Chem. Res. (M), 3329 (1998).
[9] A. O. Abdelhamid, S. M. Abdelgawad, and S. F. El-Shrarnoby, Phosphorus, Sulfur,
Silicon, and Relat. Elem., 177, 2699 (2002).
[10] D. I. Kornis, In Comprehensive Heterocyclic Chemistry, A. R. Katritzky, C. W. Rees,
and E. F. V. Scriven, Eds. (Oxford: Pergamon, 1996), Vol. 4.
[11] W. E. Kirkpatrick, T. Okabe, J. W. Hillyard, R. K. Robins, A. I. Dren, and
T. Kovenison, J. Med. Chem., 20, 386 (1977).
[12] A. J. Ryan, P. G. Welling, and S. E. Wright, Food Cosmet Toxicol., 7, 287 (1970).
[13] A. Ebnother, E. Jucker, and A. Lindeman, Helv. Chim. Acta, 42, 1201 (1959).
[14] C. S. Pak, I. K. Youn, and Y. S. Lee, Synthesis, 969 (1982).
[15] C. F. Boehringer and G. M. B. H. Soehne. German Patent 900,577, (1953); Chem.
Abstr., 52, 12927c (1953).
[16] H. F. Zohdi, N. M. Rateb, M. M. M. Sallam, and A. O. Abdelhamid, J. Chem. Res. S
(742), M(3329), 1998.
[17] G. Fravel, Bull. Soc. Chim. Fr., 31, 150 (1904).
[18] N. E. Eweiss and A. Osman, Tetrahedron Lett., 1169 (1979).
[19] A. S. Shawali, A. O. Abdelhamid, Bull. Chem. Soc. Jpn., 49, 321 (1976).
[20] A. S. Shawali and A. Osman, Tetrahedron. 27, 2517 (1971).
[21] A. O. Abdelhamid and F. H. H. El-Shiaty, Phosphorus, Sulfur, Silicon, and Related
Elem., 39, 35 (1988).