Synthesis and antimicrobial activity of some new 5-Arylazothiazole, pyrazolo[1,5-a] pyrimidine, [1,2,4]triazolo[4,3-a]pyrimidine, and pyrimido[1,2-a]benzimidazole derivatives containing the thiazole moiety

Article abstract of DOI:10.1080/10426500902922933

1-(2-(4,5-Dihydro-3-(4-methyl-2-phenylthiazol-5-yl)-5-phenylpyrazol-1-yl) -4-substituted thiazol-5-yl)-2-phenyldiazene were synthesized from hydrazonoyl halides and 3-(4-methyl-2-phenyl-1,3-thiazol-5-yl)-5-phenyl-4,5-dihydro-1H- pyrazole-1-carbothioamide in ethanolic triethylamine. Also, pyrazolo[5,1-a] pyrimidines, 2,3,6-trisubstituted pyridines, and pyrazolo[3,4-d]pyridazines were obtained from sodium salt of 3-hydroxy-1-(4-methyl-2-phenylthiazol-5-yl)prop-2- en-1-one and different heterocyclic amines. All structures of the newly synthesized compounds were elucidated by elemental analysis, spectral data, and alternative synthetic route whenever possible. The newly synthesized compounds were tested towards different microorganisms. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.

Full text of DOI:10.1080/10426500902922933

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Phosphorus, Sulfur, and Silicon and the
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Synthesis and Antimicrobial Activity
of Some New 5-Arylazothiazole,
Pyrazolo[1,5-a] Pyrimidine,
[1,2,4]Triazolo[4,3-a]Pyrimidine,
and Pyrimido[1,2-a]Benzimidazole
Derivatives Containing the Thiazole
Moiety
Abdou O. Abdelhamid a , Eman K. A. Abdelall b , Nadia A. Abdel-
Riheem a & Sayed A. Ahmed c
a Department of Chemistry, Faculty of Science, Cairo University,
Giza, Egypt
b Department of Pharmaceutical Organic Chemistry, Faculty of
Pharmacy, Beni-Suef University, Beni, Suef, Egypt
c Department of Chemistry, Faculty of Science, Beni-Suef University,
Beni, Suef, Egypt
Version of record first published: 23 Mar 2010.
To cite this article: Abdou O. Abdelhamid, Eman K. A. Abdelall, Nadia A. Abdel-Riheem & Sayed A.
Ahmed (2010): Synthesis and Antimicrobial Activity of Some New 5-Arylazothiazole, Pyrazolo[1,5-
a] Pyrimidine, [1,2,4]Triazolo[4,3-a]Pyrimidine, and Pyrimido[1,2-a]Benzimidazole Derivatives
Containing the Thiazole Moiety, Phosphorus, Sulfur, and Silicon and the Related Elements, 185:4,
709-718
To link to this article: http://dx.doi.org/10.1080/10426500902922933
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Phosphorus, Sulfur, and Silicon, 185:709–718, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500902922933
SYNTHESIS AND ANTIMICROBIAL ACTIVITY OF SOME
NEW 5-ARYLAZOTHIAZOLE, PYRAZOLO[1,5-a]
PYRIMIDINE, [1,2,4]TRIAZOLO[4,3-a]PYRIMIDINE,
AND PYRIMIDO[1,2-a]BENZIMIDAZOLE DERIVATIVES
CONTAINING THE THIAZOLE MOIETY
Abdou O. Abdelhamid,1 Eman K. A. Abdelall,2
Nadia A. Abdel-Riheem,1 and Sayed A. Ahmed3
1Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt
2Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy,
Beni-Suef University, Beni Suef, Egypt
3Department of Chemistry, Faculty of Science, Beni-Suef University,
Beni Suef, Egypt
1-(2-(4,5-Dihydro-3-(4-methyl-2-phenylthiazol-5-yl)-5-phenylpyrazol-1-yl)-4-substituted
thiazol-5-yl)-2-phenyldiazene were synthesized from hydrazonoyl halides and 3-(4-
methyl-2-phenyl-1,3-thiazol-5-yl)-5-phenyl-4,5-dihydro-1H-pyrazole-1-carbothioamide in
ethanolic triethylamine. Also, pyrazolo[5,1-a]pyrimidines, 2,3,6-trisubstituted pyridines,
and pyrazolo[3,4-d]pyridazines were obtained from sodium salt of 3-hydroxy-1-(4-methyl-
2-phenylthiazol-5-yl)prop-2-en-1-one and different heterocyclic amines. All structures of
the newly synthesized compounds were elucidated by elemental analysis, spectral data, and
alternative synthetic route whenever possible. The newly synthesized compounds were tested
towards different microorganisms.
Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental
file.
Keywords
Hydrazonoyl halides; 5-phenylazothiazoles; pyrazolines; pyrazolo[1,5-
a]pyrimidines; 2,3,6-trisubstituted pyridines
INTRODUCTION
Differently substituted pyrazolines and their derivatives are important biological
agents, and a significant amount of research activity has been directed towards this
class. In particular, they are used as antitumor,1 antibacterial, antifungal, antiviral, an-
tiparasitic, antitubercular, and insecticidal agents.2–8 Some of these compounds also have
anti-inflammatory, antidiabetic, anaesthetic, and analgesic properties.9,10 In addition, pyra-
zolopyrimidine systems are reported as inhibitors for the synthesis of DNA and RNA in
Received 28 January 2009; accepted 24 March 2009.
Address correspondence to Abdou O. Abdelhamid, Department of Chemistry, Faculty of Science, Cairo
University, Giza 12613, Egypt. E-mail: aabdou abdelhamid@yahoo.com
709

710
A. O. ABDELHAMID ET AL.
the cells of some types of cancer11 and viruses.12 We report in this article the synthe-
sis and antimicrobial studies of some new 5-arylazothiazole, pyrazolo[1,5-a]pyrimidine,
[1,2,4]triazolo[4,3-a]pyrimidine, and pyrimido[1,2-a]benzimidazole derivatives.
RESULTS AND DISCUSSION
Treatment of 1-(4-methyl-2-phenyl-1,3-thiazol-5-yl)-3-phenylprop-2-en-1-one13 (2)
with thiosemicarbazide in ethanol under reflux gave 3-(4-methyl-2-phenyl-1,3-thiazol-5-
yl)-5-phenyl-4,5-dihydro-1H-pyrazole-1-carbothioamide (3). Structure 3 was elucidated
1
by elemental analysis, spectral data, and chemical transformation. The H NMR spec-
trum of 3 showed signals at δ = 2.66 (s, 3H, CH3), 3.14–3.16 (d, 1H, J = 6 Hz,
pyrazoline) 3.32–3.35 (d, 1H, J = 6 Hz, pyrazoline), 6.00–6.02, 6.05–6.07 (q, 1H, J =
6 Hz, pyrazoline), 6.15 (s, br., 2H, NH2), 6.95–7.95 (m, 10H, ArH’s). The mass spec-
trum showed peaks m/e at 380 (M+2, 2.24%), 379 (M+1, 21.3%), 378 (M, 100%). Thus,
compound 3 reacted with C-benzoyl-N-phenylhydrazonoyl bromide in ethanolic triethy-
lamine to afford 1-(2-(4,5-dihydro-3-(4-methyl-2-phenylthiazol-5-yl)-5-phenylpyrazol-1-
yl)-4-phenylthiazol-5-yl)-2-phenyldiazene (4a) (Scheme 1). Structure 4a was confirmed
1
by elemental analysis, spectral data, and an alternate synthetic route. The H NMR spec-
trum of 4a showed signals at δ = 2.76 (2, 3H, CH3), 3.32 (dd, 1H, J = 6 Hz, pyrazo-
line), 3.90 (dd, 1H, J = 12 Hz, pyrazoline), 5.76 (dd, 1H, J = 6 Hz, pyrazoline), and
7.26–8.15 (m, 20H, ArH’s). The 13C NMR spectrum showed peaks at δ = 18.13 (CH3),
45.91 (CH2), 63.74 (CH), 119.78, 119.78, 122.35, 123.54, 126.33, 127.61, 128.11, 128.95,
129.02, 129.24, 130.30, 130.65, 132.89, 134.11, 140.74, 142.87, 148.34, 152.61, 154.89,
O
S
O
H3C
CH3
H3C
+
OHC
N
S
N
1
2
NH2NHC(S)NH2
CH3
S
NNHC(S)NH2
CH3
S
H3C
R
NH2
H
N
N=NPh
N
S
N
CH3
S
N
N
N
N
N
S
N
N
N
S
R
H3C
CH3
iii a-c
3
N
S
5a-c
6
i - PhCHO
iii
PhCHO
8a-c
N=NPh
ii- PhN2Cl
S
NNH
CH3
S
R
CH3
S
ii- PhN2Cl
N
H3C
N
N
R
N
N
a, R = C6H5
b, R = CH3
c, R = 4-methyl-2-phenylthiazol-5-yl
N
S
4a-c
7a-c
iiia = C6H5COC(Br):NNHC6H5
iiib = CH3COC(Cl):NNHC6H5
i - PhCHO
iiic = C-4-methyl-2-phenylthiazol-5-oyl-N-phenylhydrazonoyl bromide
5a-c
Scheme 1

NEW DERIVATIVES CONTAINING THE THIAZOLE MOIETY
711
163.69, 167.34. The mass spectrum of 4a showed m/e = 582 (M+). Compound 3 reacted
with ω-bromoacetophenone in ethanol to give 4,5-dihydro-3-(4-methyl-2-phenylthiazol-
5-yl)-5-phenyl-1-(4-phenylthiazol-2-yl)-1H-pyrazole (5a). The latter was coupled with
benzenediazonium chloride in alcoholic sodium acetate to afford a product identical in
all respects (mp, mixed mp, and spectra) to 4a. An unequivocal support for structure 4a
came from the reaction of each of the compounds 7a, which was prepared via 614 with
ω-bromoacetophenone, with benzaldehyde in ethanolic sodium hydroxide followed by
benzenediazonium chloride in alcoholic sodium acetate or by reaction with compound 8a,
which was prepared via reaction of 6 with C-benzoyl-N-phenyl hydrazonoyl bromide, with
benzaldehyde in ethanolic sodium hydroxide, and gave a product identical in all respects
(mp, mixed mp, and spectra) with 4a.
On the other hand, 1-(4-methyl-2-phenyl-1,3-thiazol-5-yl)ethanone (1) reacted with
ethyl formate in dried ether containing sodium methoxide to afford a sodium salt of 3-
hydroxy-1-(4-methyl-2-phenylthiazol-5-yl)prop-2-en-1-one (9). Structure 9 was confirmed
by its reactions. Thus, treatment of 3-amino-4-phenyl-1H-pyrazole in acetic acid con-
taining piperidine acetate afforded a product, namely 5-(4-methyl-2-phenylthiazol-5-yl)-
3-phenylpyrazolo[1,5-a]pyrimidine (11a) (Scheme 2). Structure 11a was elucidated by
elemental analysis, spectral data and an alternate synthetic route. The 1H NMR spectrum of
11a showed signals at δ = 2.53 (s, 3H, CH3) and 7.44–7.82 (m, 13H, ArH’s, pyrazole H-5,
pyrimidine H4 & H5). Thus, treatment of 3-(dimethylamino)-1-(4-methyl-2-phenylthiazol-
5-yl)prop-2-en-1-one (10)15 with 3-amino-4-phenylpyrazole in acetic acid and ammonium
N
N
NH2
N
N
HN
N
H3C
O
O
N
ONa
H3C
H3C
N
CH3
N
S
ix
N
S
S
i
+
HCOOC2H5
12
9
1
x
N
(CH3)NCH(OCH3)2
N
N
ii-v
H3C
N
N
S
O
X
N
N(CH3)2
H3C
N
H3C
N
Y
S
N
S
13
ii-viii
10
i - CH3ONa
11
ii- 3-amino-4-phenylpyrazole
iii- 3-amino-5-phenylpyrazole
iv = 3-amino-4-phenylamino-5-phenylcarbamoylpyrazole
v = 3-amino-4-phenylamino-5-(4-chlorophenyl)carbamoylpyrazole
vi = 3-amino-4-phenylamino-5-(4-bromophenyl)carbamoylpyrazole
vii- 3-amino-4-cyanopyrazole
viii- 3-amino-4-methyl-5-phenylpyrazole
ix-3-amino-1,2,4-triazole
x- 2-aminobenzimidazole
a, X = phenyl, Y = H
b, X = H, Y = phenyl
c, X = phenylamino, Y = phenylcarbamoyl
d, X = phenylamino, Y = (4-chlorophenyl)carbamoyl
e, X = phenylamino, Y = (4-bromophenyl)carbamoyl
f, X = cyano, Y = H
g, X = 4-methyl, Y = phenyl
Scheme 2

712
A. O. ABDELHAMID ET AL.
acetate by heating under reflux gave a product identical in all respects (mp, mixed mp,
spectra) with 11a.
Analogously, either compound 9 or 10 reacted with the appropriate 3-aminopyrazoles,
3-amino-1,2,4-triazole, or 2-aminobenzimidazole gave pyrazolo[1,5-a]pyrimidines 11b–g,
5-(4-methyl-2-phenylthiazol-5-yl)-[1,2,4]triazolo[4,3-a]pyrimidine (12), and 4-(4-methyl-
2-phenyl-4,5-dihydro-1,3-thiazol-5-yl)pyrimido[1,2-a]benzimidazole (13), respectively.
Treatment of 3-(dimethylamino)-1-(4-methyl-2-phenylthiazol-5-yl)prop-2-en-1-one
(10) with 2,4-pentanedione or ethyl 3-oxobutanoate in boiling acetic acid and ammonium
acetate under reflux gave 3-acetyl-2-methyl-6-(4-methyl-2-pheny)lthiazol-2-ylpyridine
(14) and ethyl 2-methyl-6-(4-methyl-2-phenyl)thiazol-2-ylpyridine-3-carboxylate (15),
respectively (Scheme 3).
O
O
O
H3C
O
N(CH3)2
ArN2Cl
X
H3C
NNH-Ar
N
S
N
N
N
S
S
16
10
14-15
N2H4.H2O
NH
14, X = CH3
15, X =OC2H3
N
H3C
a,Ar = C6H5
b, Ar = 4-CH3C6H4
N=N-Ph
N
S
17a
Scheme 3
Finally, treatment of the appropriate of 9 or 10 with the arenediazonium chloride in
ethanol containing sodium acetate as a buffer solution yielded 2-(2-phenylhydrazono)-3-
(4-methyl-2-phenylthiazol-5-yl)-3-oxopropanal (16a) and 2-(2-(4-tolyl)hydrazono)-3-(4-
methyl-2-phenylthiazol-5-yl)-3-oxopropanal (16b), respectively. Structure 16 was con-
1
firmed by elemental analysis, spectral data, and chemical transformation. The H NMR
spectrum of 16a showed signals at δ = 2.46 (s, 3H, CH3), 6.67–8.05 (m, 10H, ArH’s), 9.98
(s, 1H, -CHO), and 14.39 (s, br., 1H, NH). Thus, 16a was reacted with hydrazine hydrate
in boiling ethanol under reflux and gave 1-(3-(4-methyl-2-phenylthiazol-5-yl)-4H-pyrazol-
4-ylidene)-2-phenylhydrazine (17a) (Scheme 3).
PHARMACOLOGY: ANTIMICROBIAL SCREENING
Sixteen compounds were screened by the Agar dilution technique16 for their antimi-
crobial activity (see Supplemental Materials, Table S1, available online).

NEW DERIVATIVES CONTAINING THE THIAZOLE MOIETY
713
EXPERIMENTAL
All melting points were determined on an electrothermal apparatus and are uncor-
rected. IR spectra were recorded (KBr discs) on a Shimadzu FT-IR 8201 PC spectropho-
tometer. 1H NMR and 13C NMR spectra were recorded in CDCl3 and (CD3)2SO solutions
on a Varian Gemini 300 MHz spectrometer, and chemical shifts are expressed as δ using
TMS as an internal reference. Mass spectra were recorded on a GC-MS QP1000. Ele-
mental analyses were carried out at the Microanalytical Center of Cairo University. The
hydrazonoyl halides were prepared as previously described.17–19
3-(4-Methyl-2-phenyl-1,3-thiazol-5-yl)-5-phenyl-4,5-dihydro-1H-
pyrazole-1-carbothioamide 3
To a mixture of 1-(4-methyl-2-phenyl-1,3-thiazol-5-yl)-3-phenylprop-2-en-1-one (2)
(1.55 g, 5 mmol) and thiosemicarbazide (0.46 g, 5 mmol) in ethanol (20 mL), a catalytic
amount of triethylamine was added, then heated under reflux for 6 h. The resulting solid
was collected and recrystallized from ethanol to give 3 (Tables I and II).
4,5-Dihydro-3-(4-methyl-2-phenylthiazol-5-yl)-1-(4-substituted
thiazol-2-yl)-5-phenyl-1H-pyrazole 5a–c
A mixture of compound 3 (1.8 g, 5 mmol) and the appropriate of ω-
bromoacetophenone, chloroacetone, or 5-bromoacetyl-4-methyl-2-phenylthiazole
(5 mmol) in ethanol (20 mL) was heated under reflux for 2 h. The resulting solid was
neutralized with sodium bicarbonate (10%), collected, and recrystallized from ethanol to
give compounds 5a–c (Tables I and II).
1-(2-(4,5-Dihydro-3-(4-methyl-2-phenylthiazol-5-yl)-5-phenylpyrazol-1-
yl)-4-substituted thiazol-5-yl)-2-phenyldiazene 4a–c
Method A. A mixture of the appropriate hydrazonoyl halides (5 mmol), 3 (1.8 g,
5 mmol), and triethylamine (0.5 g, 0.75 mL, 5 mmol) in ethanol (20 mL) was boiled under
reflux for 2 h. The resulting solid was collected and recrystallized from DMF-EtOH mixture
to give 4a–c (Tables I and II).
Method B. An equimolar amount of the appropriate 8a–c (5mmol) and benzalde-
hyde (0.53g, 5 mmol) in ethanol (20 mL) was cooled at 5◦C, then sodium hydroxide solution
(10 mL, 4N) was added portionwise while stirring. The resulting solid was collected and
recrystallized from DMF/ethanol to give identical product in all aspects (mp, mixed mp,
and spectra) with corresponding 4a–c (Tables I and II).
Method C. A solution of benzenediazonium chloride (10 mmol) was added drop-
wise to a stirred solution of the appropriate 5a–c in ethanol (50 mL) containing sodium
acetate trihydrate (1.3g, 10 mmol) at 0–5◦C. The reaction mixture was stirred for 3 h at
0–5◦C. The resulting solid was collected and crystallized from DMF/ethanol to give 4a–c
identical in all aspects (mp, mixed mp, and spectra) with those above.
Synthesis of N-[1-(4-Methyl-2-substituted thiazol-5-yl)-ethylidene]-N’-
(4-phenyl-thiazol-2-yl)-hydrazine 7a–c
A mixture of 6 (1.45 g, 5 mmol) and the appropriate of ω-bromoacetophenone,
chlroacetone, or 5-bromoacetyl-4-methyl-2-phenylthiazole (5 mmol) in ethanol (20 mL)

714
A. O. ABDELHAMID ET AL.
Table I Characterization data of the newly synthesized compounds
% Analyses, Calcd./ Found
Mol. Formula/
Mol. Wt.
Color/
Yield%
Mp, ◦C/
Solvent
Compd.
No.
S
N
H
C
16.94
16.78
11.00
10.82
12.32
12.22
14.15
14.01
15.39
15.17
13.40
13.21
16.70
16.58
16.42
16.23
19.52
19.30
19.72
19.63
12.96
12.91
14.82
14.69
16.25
16.19
8.70
8.57
8.70
8.50
6.38
6.54
5.97
6.12
5.51
5.25
10.10
9.90
8.38
8.42
10.93
11.12
9.35
14.80
14.61
14.42
14.72
16.14
16.01
14.42
14.30
13.45
13.21
11.70
11.50
12.16
12.21
14.35
14.20
17.06
17.09
14.36
14.21
16.99
16.67
19.43
19.43
16.57
16.52
15.21
15.10
15.21
15.00
16.72
16.85
15.65
15.56
14.45
14.65
22.07
21.85
14.65
14.56
23.87
23.95
16.36
16.46
9.08
4.79
4.82
4.40
4.35
4.65
4.60
4.30
4.14
4.84
4.62
4.63
4.55
4.38
4.50
4.65
4.60
4.91
5.72
4.34
4.49
4.48
4.56
4.66
4.50
4.26
4.22
4.38
4.22
4.38
4.28
4.41
4.32
3.94
4.12
3.64
3.75
3.49
3.56
4.74
4.85
3.78
3.87
4.12
3.90
5.23
5.32
5.36
5.52
4.33
4.35
4.71
4.65
4.38
4.52
63.47
63.33
70.08
69.85
66.90
66.81
67.13
67.30
66.32
66.45
70.26
70.10
66.75
66.58
64.59
64.42
58.51
58.20
61.57
61.33
65.56
65.55
61.09
61.00
62.92
62.78
71.72
71.60
71.72
71.55
69.31
69.51
64.86
64.74
59.90
60.12
64.34
64.34
72.23
72.13
61.42
61.66
70.15
70.00
70.10
70.20
67.43
67.34
65.31
65.23
66.10
66.20
66.07
66.12
C20H18N4S2
378.5
C34H26N6S2
582.74
C29H24N6S2
520.67
C38H29N7S3
679.87
Yellow
80
Violet
86
Violet
82
Violet
80
Brown
66
Orange
69
Orange
62
Brown
80
Green
90
Brown
69
Red
80
Red
82
Red
69
Yellow
75
Orange
89
Yellow
66
Yellow
66
Orange
70
Pale yellow
85
Yellow
78
Colorless
82
Yellow
78
Colorless
77
Colorless
67
Orange
78
Orange
75
Pale yellow
68
210–213
EtOH
3
254–256
DMF/EtOH
248–250
DMF/EtOH
262–263
DMF/EtOH
192–195
EtOH
202–204
EtOH
195–197
EtOH
145–147
EtOH
151–153
EtOH
161–163
EtOH
164–166
EtOH
4a
4b
4c
C
23H20N5
416.56
5a
C28H22N4S2
478.63
C32H25N5S3
575.76
C21H18N4S2
390.52
C16H16N4S2
494.63
C25H21N5S3
487.66
C27H22N6S2
494.63
C22H20N6S2
432.56
C31H25N7S3
591.77
C22H16N4S
368.4
C22H16N4S
368.4
C29H22N6OS
502.58
C29H21 ClN6OS
537.05
C29H21 BrN6OS
581.50
C17H11N5S
317.35
C23H18N4S
382.49
C15H11N5S
293.35
5b
5c
7a
7b
7c
8a
119–121
EtOH
143–145
EtOH
149–150
EtOH
238–240
DMF
8b
8c
11a
11b
11c
11d
11e
11f
11g
12
260–261
EtOH
245–247
DMF/EtOH
263–265
DMF/EtOH
252–255
AcOH
154–157
Benzene
190–192
AcOH
160–163
AcOH
138–140
EtOH
80–81
EtOH
C20H14N4S
342.43
C18H16N2OS
308.41
C19H18N2O2S
338.43
C19H15 N3O2S
349.41
C20H17 N3O2S
363.44
C19H15N5S
345.43
13
9.53
10.40
10.25
9.47
9.57
9.18
9.00
4.71
4.60
9.28
14
9.12
8.28
8.42
12.03
11.85
11.56
11.45
20.27
20.05
15
222–224
EtOH
232–235
EtOH
254–257
EtOH
16a
16b
17a
9.34

NEW DERIVATIVES CONTAINING THE THIAZOLE MOIETY
715
Table II Spectral data of some newly synthesized compounds
Compound
No.
Spectral data
IR: 3380, 2160 (NH2), 3056, 2980 (CH, aromatic and aliphatic), 1623 (C N), 1370 (CH3),
1430 (CH2).
3
1H NMR: δ = 2.66 (s, 3H, CH3), 3.14–3.16 (d, 1H, J = 6 Hz, pyrazoline) 3.32–3.35 (d, 1H,
J = 6 Hz, pyrazoline), 6.00–6.02, 6.05–6.07 (q, 1H, J = 6 Hz, pyrazoline), 6.15 (s, br., 2H,
NH2), 6.95–7.95 (m, 10H, ArH’s). Ms: m/e = 380 (M+2, 2.24%), 379 (M+1, 21.3%), 378
(M, 100%).
IR: 3051, 2994 (CH, aromatic and aliphatic), 1623 (C N), 1370 (CH3), 1433 (CH2).
1H NMR: δ = 2.76 (2, 3H, CH3), 3.32 (dd, 1H, J = 6 Hz, pyrazoline), 3.90 (dd, 1H, J = 12
Hz, pyrazoline), 5.76 (dd, 1H, J = 6 Hz, pyrazoline) and 7.26–8.15 (m, 20 H, ArH’s).
13C NMR: δ = 18.13 (CH3), 45.91 (CH2), 63.74 (CH), 119.78, 119.78, 122.35, 123.54,
126.33, 127.61, 128.11, 128.95, 129.02, 129.24, 130.30, 130.65, 132.89, 134.11, 140.74,
142.87, 148.34, 152.61, 154.89, 163.69, 167.34.
4a
Ms: m/e = 582 (M).
IR: 3050, 2990 (CH, aromatic and aliphatic), 1623 (C N), 1365 (CH3), 1435 (CH2).
1H NMR: δ = 2.42 (s, 3H, CH3CO), 2.76 (2, 3H, CH3), 3.32 (dd, 1H, J = 6 Hz, pyrazoline),
3.90 (dd, 1H, J = 12 Hz, pyrazoline), 5.76 (dd, 1H, J = 6 Hz, pyrazoline) and 7.26–8.15
(m, 15 H, ArH’s).
4b
1H NMR: δ = 2.76 (s, 6H, 2-CH3), 3.32 (dd, 1H, J = 6 Hz, pyrazoline), 3.90 (dd, 1H, J = 12
Hz, pyrazoline), 5.76 (dd, 1H, J = 6 Hz, pyrazoline) and 7.26—8.15 (m, 20 H, ArH’s).
IR: 3056, 2992 (CH, aromatic and aliphatic), 1623 (C N), 1345 (CH3), 1437 (CH2).
1H NMR: δ = 2.42 (s, 3H, CH3CO), 2.76 (2, 3H, CH3), 3.32 (dd, 1H, J = 6 Hz, pyrazoline),
3.90 (dd, 1H, J = 12 Hz, pyrazoline), 5.76 (dd, 1H, J = 6 Hz, pyrazoline) and 7.26–8.15
(m, 17 H, ArH’s).
4c
5a
IR: 3058, 2985 (CH, aromatic and aliphatic), 1623 (C N), 1370 (CH3), 1440 (CH2).
1H NMR: δ = 2.76 (2, 3H, CH3), 3.32 (dd, 1H, J = 6 Hz, pyrazoline), 3.90 (dd, 1H, J = 12
Hz, pyrazoline), 5.76 (dd, 1H, J = 6 Hz, pyrazoline) and 7.26–8.15 (m, 16 H, ArH’s).
IR: 3056, 2980 (CH, aromatic and aliphatic), 1623 (C N), 1370 (CH3), 1440 (CH2).
1H NMR: δ = 2.76 (s, 6H, 2-CH3), 3.32 (dd, 1H, J = 6 Hz, pyrazoline), 3.90 (dd, 1H, J = 12
Hz, pyrazoline), 5.76 (dd, 1H, J = 6 Hz, pyrazoline) and 7.26–8.15 (m, 16 H, ArH’s).
IR: 3350 (NH), 3056, 2988 (CH, aromatic and aliphatic), 1623 (C N), 1350 (CH3).
1H NMR: δ = 2.29 (s, 3H, CH3), 2.59 (s, 3H, CH3), 7.16 (s, 1H, thiazole H-5), 7.27–7.89 (m,
10 H, ArH’s) and 8.99 (s, br., 1H, NH).
IR: 3350 (NH), 3056, 2993 (CH, aromatic and aliphatic), 1623 (C N), 1356 (CH3).
1H NMR: δ = 2.19 (s, 3H, CH3), 2.29 (s, 3H, CH3), 2.59 (s, 3H, CH3), 7.16 (s, 1H, thiazole
H-5), 7.67–7.89 (m, 5 H, ArH’s) and 8.62 (s, br., 1H, NH).
IR: 3350 (NH), 3050, 2987 (CH, aromatic and aliphatic), 1623 (C N), 1360 (CH3).
1H NMR: δ = 2.29 (s, 3H, CH3), 2.46 (s, 3H, CH3), 2.59 (s, 3H, CH3), 6.96 (s, 1H, thiazole
H-5), 7.66–7.88 (m, 10 H, ArH’s) and 8.99 (s, br., 1H, NH).
5b
5c
7a
7b
7c
IR: 3350 (NH), 3056, 2988 (CH, aromatic and aliphatic), 1623 (C N), 1340 (CH3).
1H NMR: δ = 2.29 (s, 3H, CH3), 2.59 (s, 3H, CH3), 7.37–8.00 (m, 15 H, ArH’s) and 9.74 (s,
br., 1H, NH).
IR: 3350 (NH), 3062, 2980 (CH, aromatic and aliphatic), 1623 (C N), 1350 (CH3).
1H NMR: δ = 2.29 (s, 3H, CH3), 2.54 (s, 3H, CH3), 2.59 (s, 3H, CH3), 7.50–8.07 (m, 10 H,
ArH’s) and 8.89 (s, br., 1H, NH).
IR: 3350 (NH) 3050, 2985 (CH, aromatic and aliphatic), 1623 (C N), 1347 (CH3).
1H NMR: δ = 2.29 (s, 3H, CH3), 2.46 (s, 3H, CH3), 2.59 (s, 3H, CH3), 7.50–7.08 (m, 15 H,
ArH’s) and 9.47 (s, br., 1H, NH).
8a
8b
8c
IR: 3310 (NH) 3066, 2992 (CH, aromatic and aliphatic), 1623 (C N), 1340 (CH3).
1H NMR: δ = 2.46 (s, 3H, CH3), 6.53 (s, 1H, pyrazole H-4), 7.13 (d, 1H, J = 4Hz, pyrimidine
H-5), 7.46–7.82 (m, 10H, ArH’s) and 8.74 (d, 1H, 8Hz, pyrimidine H-6).
11a
(Continued on next page)

716
A. O. ABDELHAMID ET AL.
Table II Spectral data of some newly synthesized compounds (Continued)
Compound
No.
Spectral data
IR: 3320 (NH), 3050, 2990 (CH, aromatic and aliphatic), 1623 (C N), 1340 (CH3).
1H NMR: δ = 2.46 (s, 3H, CH3), 6.90 (d, 2H, J = 8H, ArH’s), 7.14 (d, 1H, J = 4Hz, pyrimidine
H-5), 7.56–7.78 (m, 8H, ArH’s), 8.74 (d, 1H, 8Hz, pyrimidine H-6 and 9.05 (s, 1H, pyrazole H-3).
IR: 3299 (NH), 3065, 2994 (CH, aromatic and aliphatic), 1662 (CO), 1623 (C N), 1340 (CH3).
1H NMR: δ = 2.46 (s, 3H, CH3), 6.98 (d, 2H, J = 8H, pyrimidine H-5), 7.07–8.00 (m, 15H, ArH’s),
8.49 (d, 1H, 8Hz, pyrimidine H-6) and 11.34 (s, br., 1H, 2NH).
IR: 3299 (NH), 3056, 2980 (CH, aromatic and aliphatic), 1662 (CO), 1623 (C N), 1340 (CH3).
1H NMR: δ = 2.46 (s, 3H, CH3), 6.98 (d, 2H, J = 8H, pyrimidine H-5), 7.07–8.00 (m, 14H, ArH’s),
8.49 (d, 1H, 8Hz, pyrimidine H-6) and 11.34 (s, br., 1H, 2NH).
11b
11c
11d
11e
11f
IR: 3299 (NH), 3056, 2990 (CH, aromatic and aliphatic), 1665 (CO), 1620 (C N), 1340 (CH3).
1H NMR: δ = 2.46 (s, 3H, CH3), 6.98 (d, 2H, J = 8H, pyrimidine H-5), 7.07–8.00 (m, 14H, ArH’s),
8.49 (d, 1H, 8Hz, pyrimidine H-6) and 11.34 (s, br., 1H, 2NH).
IR: 3056, 2996 (CH, aromatic and aliphatic), 2160 (CN), 1623 (C N), 1340 (CH3).
1H NMR: δ = 2.46 (s, 3H, CH3), 7.35 (d, 2H, J = 8H, pyrimidine H-5), 7.62–7.79 (m, 5H. ArH’s),
9.23 (s, 1H, pyrazole H-5), and 9.50 (d, 1H, 8Hz, pyrimidine H-6).
1H NMR: δ = 2.46 (s, 3H, CH3), 2.47 (s, 3H, CH3), 7.11 (d, 2H, J = 8H, pyrimidine H-5),
11g
12
7.23–7.85 (m, 10H, ArH’s) and 8.60 (d, 1H, 8Hz, pyrimidine H-6).
1H NMR: δ = 2.46 (s, 3H, CH3), 6.99 (d, 2H, J = 4H, pyrimidine H-5), 7.62–7.79 (m, 5H, ArH’s),
9.01 (d, 4H, 8Hz, pyrimidine H-6) and 9.57 (s, 1H, triazole H-5).
1H NMR: δ = 2.46 (s, 3H, CH3), 7.26 (d, 2H, J = 8H, pyrimidine H-5), 7.32–7.94 (m, 9H, ArH’s)
13
and 8.88 (d, 4H, 8Hz, pyrimidine H-6)
IR: 3056, 2980 (CH, aromatic and aliphatic), 1675 (CO), 1623 (C N), 1340 (CH3).
1H NMR: δ = 2.49 (s, 3H, CH3), 2.62 (s, 3H, CH3), 2.66 (s, 3H, CH3), 7.62–7.76 (m, 5H, ArH’s),
7.86 (d, 1H, 4Hz, pyridine H-5) and 7.06 (d, 1H, 4Hz, pyridine H-6).
IR: 3056, 2980 (CH, aromatic and aliphatic), 1713 (CO), 1623 (C N), 1340 (CH3).
1H NMR: δ = 1.34 (t, J = 7Hz, CH2CH3), 2.73 (s, 3H, CH3), 2.75 (s, 3H, CH3), 4.31 (q, J = 7H,
CH2CH3), 7.62–7.92 (m, 5H, ArH’s), 8.98(d, 1H, 4Hz, pyridine H-5) and 8.29 (d, 1H, 4Hz,
pyridine H-6).
14
15
IR: 32280 (NH), 3056, 2980 (CH, aromatic and aliphatic), 2870, 2780 (CH), 1690 (CO), 1340
(CH3).
16a
16b
17a
1H NMR: δ = 2.46 (s, 3H, CH3), 7.28–8.05 (m, 10H, ArH’s), 9.75 (s, 1H, CHO) and 15.09 (s, 1H,
br., NH).
IR: 32280 (NH), 3056, 2980 (CH, aromatic and aliphatic), 2870, 2780 (CH), 1690 (CO), 1340
(CH3).
1H NMR: δ = 2.33 (s, 3H, CH3), 2.46 (s, 3H, CH3), 7.44–8.05 (m, 9H, ArH’s), 9.75 (s, 1H, CHO)
and 15.09 (s, 1H, br., NH).
IR: 32280 (NH), 3056, 2980 (CH, aromatic and aliphatic), 1340 (CH3).
1H NMR: δ = 2.60 (s, 3H, CH3), 6.85–8.12 (m, 11H, ArH’s and pyrazole H-5), and 11.40 (s, 1H,
br., NH).
was heated under reflux for 2 h. The resulting solid was collected and recrystallized from
the proper solvent to give compounds 7a–c (Tables I and II).
Sodium Salt of 3-Hydroxy-1-(4-methyl-2-phenylthiazol-5-yl)prop-2-en-
1-one 9
A mixture of 1-(4-methyl-2-phenyl-thiazol-5-yl)ethanone (2.17 g, 10 mmol) and ethyl
formate (0.74 g, 10 mmol) in dry ether (20 mL) was added portionwise while stirring to

NEW DERIVATIVES CONTAINING THE THIAZOLE MOIETY
717
solution sodium methoxide (0.54 g, 10 mmol) in dry ether (10 mL) at 0–5◦C. The resulting
solid was collected, dried, and was used without purification.
N-[1-(4-Methyl-2-substituted thiazol-5-yl)-ethylidene]-N’-(4-phenyl-5-
phenylazo-thiazol-2-yl)-hydrazine 8a–c
A mixture of 6 (1.45 g, 5 mmol), the appropriate hydrazonoyl halides iiia–c, and
triethylamine (0.75 mL, 5 mmol) in ethanol (20 mL) was heated under reflux for 2 h.
The resulting solid was collected and recrystallized from the proper solvent to give 8a–c
(Tables I and II).
Pyrazolo[5,1-a]pyrimidines 11a–g, [1,2,4]Triazolo[4,3-a]pyrimidine 12,
Pyrimido[1,2-a]benzimidazole 13, and Pyridines 14, 15
Method A. A mixture of the sodium salt 9 (1.2g, 5 mmol) and the appropri-
ate amount of 3-amino-4-phenylpyrazole, 3-amino-5-phenylpyrazole, 3-amino-4-phenylcar
bamoyl-5-phenylaminopyrazole, 3-amino-4-(4-chlorophenyl)carbamoyl-5-phenylaminopy
razole, 3-amino-4-(4-bromophenyl)carbamoyl-5-phenylaminopyrazole, 3-amino-4-cyano
pyrazole, 3-amino-4-methyl-5-phenylpyrazole, 3-amino-1,2,4-triazole, 2-aminobenzimida
zole, acetylacetone, or ethyl acetoacetate (5 mmol) in a solution of piperidine acetate
[piperidine (2.5 mL)], water (5 mL), and acetic acid (2.5 mL) was heated under reflux for
about 10 min. Then acetic acid (1.5 mL) was added while boiling, and the resulting solid
was collected and recrystallized from the appropriate solvents (Tables I and II).
Method B. An equimolar amount of 10 (1.02 g, 5 mmol), the appropriate amount
of 3-amino-4-phenylpyrazole, 3-amino-5-phenylpyrazole, 3-amino-4-phenylcarbamoyl-5-
phenylaminopyrazole, 3-amino-4-(4-chlorophenyl)carbamoyl-5-phenylaminopyrazole, 3-
amino-4-(4-bromophenyl)carbamoyl-5-phenylaminopyrazole, 3-amino-4-cyanopyrazole,
3-amino-4-methyl-5-phenylpyrazole, 3-amino-1,2,4-triazole, 2-aminobenzimidazole,
acetylacetone, or ethyl acetoacetate (5 mmol) and ammonium acetate (5 mmole) in acetic
acid (10 mL) was heated under reflux for 4 h. The resulting solid was collected and
recrystallized from the proper solvent to give products (Tables I and II).
2-(2-Arylhydrazono)-3-(4-methyl-2-phenylthiazol-5-yl)-3-oxopropanal
16a,b
Arenediazonium chloride (5 mmol) was added to the appropriate cold solution of 9
or 10 (5 mmol) and sodium acetate (0.65 g, 5 mmol) in ethanol (50 mL) while stirring. The
crude solid was collected and recrystallized from ethanol to give 16 (Tables I and II).
(1-(3-(4-Methyl-2-phenylthiazol-5-yl)-4H-pyrazol-4-ylidene)-2-
phenylhydrazine 17a
An equimolar amount of 16a and hydrazine hydrate (5 mmole) in ethanol (20 mL)
was boiled under refluxed for 15 min. The resulting solid was collected and recrystallized
from the proper solvent to give the pyrazole 17a (Tables I and II).

718
A. O. ABDELHAMID ET AL.
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