Reactions with hydrazonoyl halides 62: Synthesis and antimicrobial evaluation of some new imidazo [1,2-a]pyrimidine, imidazo [1,2-a]pyridine, imdazo [1,2-b]pyrazole, and quinoxaline derivatives

Article abstract of DOI:10.1002/jhet.307

(Chemical Equation Presented) 3-Arylazo-2-(4-methyl-2-phenylthiazol-5-yl) imidazo[1,2-a]pyrimidine, 2-(4-methyl-2-phenyl-1,3-thiazol-5-yl)-3- phenylazoimidazo[1,2-a]pyridine, 3-arylazo-2-(4-methyl-2-phenylthiazol-5-yl)-6- phenyl-5Himidazo[1,2-b]pyrazole, 6-(4-methyl-2-phenyl-thiazol-5-yl)-5- phenylazo3-phenyl-imidazo[2,1-b]thiazole, 3-(4-methyl-2-phenylthiazol-5-yl)-2- phenylhydrazino-(1H)-quinoxaline, 3-(4-methyl-2-phenylthiazol-5-yl)- 2-phenylazoquinoxaline, 3-(4-methyl-2-phenylthiazol-5-yl)-2- phenylhydrazinobenzo-[1,4] thiazine, 3-(4-methyl-2-phenyl-thiazol-5-yl)-2- phenylhydrazinobenzo[1,4]oxazine, and 3-(4-methyl-2-phenylthiazol-5-yl)-2- phenylazo-1H-pyrido[2,3-b]pyrazine derivatives were synthesized via reaction of 2-(4-methyl-2-phenyl-1,3-thiazol-5-yl)-2-oxo-N-arylethanehydrazonoyl bromide with each of 2-aminopyrimidine, 2-aminopyridine, 3-aminopyrazoles, 2-amino-4-phenylthiazole, o-phenylenediamine, o-aminothiophenol, o-aminophenol, or 2, 3-diaminopyridine, respectively. All structures of the newly synthesized compounds were elucidated by elemental analysis, spectral data, and alternative synthetic route whenever possible. The entire newly synthesized compounds are tested toward different microorganisms.

Full text of DOI:10.1002/jhet.307

March 2010
Reactions with Hydrazonoyl Halides 62: Synthesis and
Antimicrobial Evaluation of Some New Imidazo
[1,2-a]pyrimidine, Imidazo [1,2-a]pyridine, Imdazo
[1,2-b]pyrazole, and Quinoxaline Derivatives
477
Abdou O. Abdelhamid,a* Eman K. A. Abdelall,b and Yasser H. Zakic
aDepartment of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt
bDepartment of Organic Chemistry, Faculty of Pharmacy, Beni-Suef University, Egypt
cDepartment of Chemistry, Faculty of Science, Beni-Suef University, Egypt
*E-mail: abdelhamid45@yahoo.com
Received August 1, 2009
DOI 10.1002/jhet.307
Published online 23 February 2010 in Wiley InterScience (www.interscience.wiley.com).
3-Arylazo-2-(4-methyl-2-phenylthiazol-5-yl)imidazo[1,2-a]pyrimidine, 2-(4-methyl-2-phenyl-1,3-thia-
zol-5-yl)-3-phenylazoimidazo[1,2-a]pyridine, 3-arylazo-2-(4-methyl-2-phenylthiazol-5-yl)-6-phenyl-5H-
imidazo[1,2-b]pyrazole, 6-(4-methyl-2-phenyl-thiazol-5-yl)-5-phenylazo3-phenyl-imidazo[2,1-b]thiazole,
3-(4-methyl-2-phenylthiazol-5-yl)-2-phenylhydrazino-(1H)-quinoxaline, 3-(4-methyl-2-phenylthiazol-5-
yl)- 2-phenylazoquinoxaline, 3-(4-methyl-2-phenylthiazol-5-yl)-2-phenylhydrazinobenzo-[1,4] thiazine,
3-(4-methyl-2-phenyl-thiazol-5-yl)-2-phenylhydrazinobenzo[1,4]oxazine, and 3-(4-methyl-2-phenyl-
thiazol-5-yl)-2-phenylazo-1H-pyrido[2,3-b]pyrazine derivatives were synthesized via reaction of 2-(4-methyl-
2-phenyl-1,3-thiazol-5-yl)-2-oxo-N-arylethanehydrazonoyl bromide with each of 2-aminopyrimidine, 2-ami-
nopyridine, 3-aminopyrazoles, 2-amino-4-phenylthiazole, o-phenylenediamine, o-aminothiophenol, o-amino-
phenol, or 2, 3-diaminopyridine, respectively. All structures of the newly synthesized compounds were
elucidated by elemental analysis, spectral data, and alternative synthetic route whenever possible. The entire
newly synthesized compounds are tested toward different microorganisms.
J. Heterocyclic Chem., 47, 477 (2010).
INTRODUCTION
amino-4-phenylthiazole, o-phenylenediamine, o-amino-
thiophenol, o-aminophenol, and 2,3-diaminopyridine.
Our continuous interest in the chemistry of hydrazo-
noyl halides [1–9] originates from our persistent trials to
obtain pyridines, pyrimidines, pyridazines, and their ana-
logs. The importance of such compounds lies in their
diverse pharmaceutical activities, namely antibacterial
[10,11], antidiabetic [12], anti-HIV [13], antiviral
[14,15], and analgesic activities. We report herein the
reactivity of 2-(4-methyl-2-phenyl-1,3-thiazol-5-yl)-2-
oxo-N-arylethanehydrazonoyl bromides toward 2-amino-
pyrimidine, 2-aminopyridine, 3-aminopyrazoles, 2-
RESULTS AND DISCUSSION
Treatment of 2-aminopyrimidine (2) with the appro-
priate 2-(4-methyl-2-phenylthiazol-5-yl)-2-oxo-N-aryle-
thanehydrazonoyl bromide (1a, b) in ethanol gave 3-
arylazo-2-(4-methyl-2-phenylthiazol-5-yl)imidazo[1,2-a]
pyrimidine (3a, b) in a good yield (Scheme 1). Struc-
ture 3 was elucidated by elemental analysis, spectral
C
V
2010 HeteroCorporation

478
A. O. Abdelhamid, E. K. A. Abdelall, and Y. H. Zaki
Vol 47
Scheme 1
1
data, and alternative synthesis. H-NMR spectrum of 3a
showed signals at d ¼ 2.46 (s, 3H, 4-methylthiazole),
6.86–6.70 (t, 3H, pyrimidine H-5), 7.36–7.37 (d, 2H,
ArH), 7.62–7.67 (m, 3H, ArH), 7.70–7.81 (m, 3H,
ArH), 8.53–8.54 (d, 1H, pyrimidine H-4), 8.65–8.66 (d,
1H, pyrimidine H-6). Its IR (cmꢀ1) spectrum revealed
bands at 3060, 2923 (CH), 1645 (C¼¼N), 1599 (C¼¼C),
1321 (CH3), and no band between 1800 and 1650 cmꢀ1
attributed the absence of carbonyl group. Thus, treat-
ment of 2-(4-methyl-2-phenylthiazol-5-yl)imidazo[1,2-
a]pyrimidine (4), which was synthesized via reaction of
2-aminopyrimidine with 2-bromo-1-(4-methyl-2-phenyl-
1,3-thiazol-5-yl)ethanone, with the appropriate arene-
diazonium chloride in ethanolic sodium acetate gave a
product identical in all aspects (mp., mixed mp., and
spectra) with 3a and 3b, respectively.
Analogously, the appropriate 2-aminopyridine, 3-amino-
5-phenylpyrazole, 3-amino-4-methyl-5-phenylpyrazole, or 2-
Scheme 2
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March 2010 Reactions with Hydrazonoyl Halides 62: Synthesis and Antimicrobial Evaluation of Some New
Imidazo[1,2-a]pyrimidine, Imidazo[1,2-a]pyridine, Imdazo[1,2-b]pyrazole, and Quinoxaline Derivatives
479
Scheme 3
amino-4-phenylthiazole was reacted with 2-(4-methyl-2-phe-
nyl-1,3-thiazol-5-yl)-2-oxo-N-phenylethanehydrazonoyl bro-
mide (1a) in boiling ethanol gave 3-phenylazo-2-(4-methyl-
2-phenylthiazol-5-yl)imidazo[1,2-a]pyridine (5), 3-phenyl-
azo-2-(4-methyl-2-phenyl-thiazol-5-yl)-6-phenyl-5H-imidazo
[1,2-b]pyrazole (6a), 2-(4-methyl-2-phenyl-thiazol-5-yl)-
5-methyl-6-phenyl-3-phenylazo-5H-imidazo[1,2-b]pyrazole
(6b), and 6-(4-methyl-2-phenyl-thiazol-5-yl)-5-phenylazo3-
phenylimidazo[2,1-b]thiazole (7), respectively (Scheme 2).
Structures 5–7 were elucidated by elemental analyses,
spectral data, and alternative synthetic route. Thus, treat-
ment of 2-(4-methyl-2-phenylthiazol-5-yl)-6-phenyl-1H-
imidazo[1,2-b]pyrazole (8), which was synthesized from
2-bromo-1-(4-methyl-2-phenyl-1,3-thiazol-5-yl)ethanone
with 3(5)-amino-5(3)-phenylpyrazole in boiling ethanol,
with benzenediazonium chloride in ethanolic sodium ac-
etate solution gave product identical in all aspects (mp.,
mixed mp., and spectra) with 6a.
uct exhibits in ethanol two bands at knm ¼ 315 (log e ¼
3.3416) and 466 (log e ¼ 4.1734). Such an absorption
pattern is similar to that of typical azo-form [16,17].
M.O. calculation using HyperChem semi-empirical
method AM1, for structure 6A, showed E ¼ ꢀ6034.948
kcal/mol and heat formation ¼ 365.522 kcal/mol, for
structure 6B showed E ¼ ꢀ6096.498 kcal/mol and heat
formation ¼ 303.972 kcal/mol, and for structure 6a,
E ¼ ꢀ6113.009 kcal/mol and heat formation ¼ 287.460
kcal/mol. These results indicted that the structure 6a
was more compatible tautomeric form.
Treatment of 1a with o-phenylenediamine in boiling
ethanol under reflux gave 3-(4-methyl-2-phenylthiazol-
5-yl)-2-phenylhydrazino-(1H)-quinoxaline (9). Structure
9 was confirmed by elemental analysis, spectral data,
and its oxidation with hydrogen peroxide in acetic acid
to afford 3-(4-methyl-2-phenyl-thiazol-5-yl)-2-phenyla-
zoquinoxaline (10) (Scheme 3).
Attention was then turned to the tautomeric structure
of the product 6a as they can exist in the tautomeric hy-
drazone form A or phenylazoenamine form B (Scheme
Analogously, treatment of 1a with the appropriate of
each of 2-aminothiophenol, 2-aminophenol, or 2,3-dia-
minopyridine gave 3-(4-methyl-2-phenyl-thiazol-5-yl)-2-
phenylhydrazinobenzo[1,4]thiazine (11), 3-(4-methyl-2-
phenyl-thiazol-5-yl)-2-phenylhydrazinobenzo[1,4]oxazine
(12), and 1-(1,4-dihydro-3-(4-methyl-2-phenylthiazol-5-yl)-
2-phenylazopyrido[2,3-b]pyrazine (13), respectively. Struc-
tures 11A and 12A were ruled out according to
UV spectra. Thus, UV spectra of 11 and 12 exhibit
1
2). Unfortunately, their spectra (IR and H-NMR) were
not of too much help to decide the actual tautomeric
form of the compound in question. This problem was
solved by examining UV spectrum and M.O. calcula-
tion. The electronic absorption of compound 6a in etha-
nol was also compatible with the azo form B. The prod-
Journal of Heterocyclic Chemistry
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480
A. O. Abdelhamid, E. K. A. Abdelall, and Y. H. Zaki
Vol 47
Table 1
Response of various microorganisms to some synthesized compounds in vitro culture.
Comp no.
S. aureus
B. subitis
E. coli
Ps. aeruginosa
C. albicans
3a
3b
4
5
6a
6b
7
8
9
10
11
12
13
ꢂ1600
ꢂ1600
ꢂ1600
ꢂ800
ꢂ800
ꢂ800
ꢂ400
ꢂ800
ꢂ800
ꢂ800
ꢂ400
ꢂ800
ꢂ400
ꢂ400
ꢂ800
ꢂ400
ꢂ400
>400
ꢃ25
ꢂ800
ꢂ800
ꢂ800
ꢂ800
ꢂ400
ꢂ800
ꢂ800
ꢂ800
ꢂ800
ꢂ400
ꢂ800
ꢂ400
ꢂ800
>800
ꢃ25
ꢂ400
ꢂ800
ꢂ800
ꢂ400
ꢂ800
ꢂ400
ꢂ800
ꢂ800
ꢂ400
ꢂ800
ꢂ800
ꢂ400
ꢂ400
>800
400
ꢂ400
ꢂ400
ꢂ800
ꢂ800
>800
ꢂ400
ꢂ800
ꢂ400
ꢂ800
ꢂ800
ꢂ400
ꢂ800
ꢂ800
>400
ꢂ800
ꢃ25
ꢂ800
ꢂ1600
ꢂ1600
ꢂ1600
ꢂ1600
ꢂ1600
ꢂ1600
ꢂ1600
ꢂ1600
>1600
ꢃ100
DMSO
Ciprofloxacin
Triflucan
ꢂ800
ꢂ800
ꢂ800
ꢂ800
kmax ¼ 357 (log e ¼ 4.022) and 345 (log e ¼ 2.716),
whereas spectrum of 13 exhibits two bands at kmax ¼ 345
(log e ¼ 4.0177) and 466 (log e ¼ 4.6467).
compounds. S. aureus was the most resistant organism.
Some compounds showed antibacterial activity, whereas
others showed antifungal activity.
Antimicrobial screening. Ten selected compounds
were screened for their antimicrobial activity using five
selected standard isolates, which have been chosen as
representative examples of different types of microor-
ganisms as follows: Gram-positive both nonsporulated
bacteria as Staphylococus aureus and sporulated as Ba-
cillus subtilis, Gram-negative as Escherichia coli and
Pseudomonas aeruginosa, and a fungus as Candida
albicans.
Method: Agar dilution technique. The appropriate vol-
ume of membrane filtered stock solution of 0.05 g/5 mL
of each compound was prepared by the twofold dilution
method to obtain the concentrations: 400, 200, 100, 50,
and 25 lg/mL [18]. The volumes were added to the
molten LB agar (about 50ꢁC). After mixing, the media
were allowed to harden and dry by placing in an incuba-
tor at 37ꢁC for 10 min. Plates containing serial dilutions
of each compound were inoculated with a sterile multi-
inoculator onto the surface of the agar medium so that
the final inoculum of each isolate on the agar surface
was in the order of 104–105 CFU/spot. Ciprofloxacin
and triflucan were used as positive controls and the sol-
vent, dimethylsulfoxide (DMSO), as negative control.
Minimum inhibitory concentrations (MICs) were read
after 18 h incubation at 37ꢁC for bacteria and 25ꢁC for
fungus. The MIC is reported as the lowest concentration
of the compound that prevents the growth of visible col-
onies. The obtained MICs of 10 representative examples
are presented in Table 1.
EXPERIMENTAL
All melting points were determined on an electrothermal ap-
paratus and are uncorrected. IR spectra were recorded (KBr
discs) on a Shimadzu FTIR 8201 PC Spectrophotometer. 1H-
NMR and 13C-NMR spectra were recorded in CDCl3 solution
on a Varian Mercury 300 MHz spectrometer, and chemical
shifts are expressed as d using TMS as an internal reference.
The ultraviolet spectrum was recorded using Shimadzu UV–
vis 1601 PC double beam spectrophotometer. Mass spectra
were recorded on a GC-MS QP1000. Elemental analyses were
carried out at the Micro analytical center of Cairo University.
The hydrazidoyl bromides 1(a, b) were prepared as previously
reported [19].
General procedure for the synthesis of (3a, b), (5), (6a,
b), (7), (9), (11), (12), and (13). A mixture of the appropriate
hydrazonoyl bromide 1a, b (5 mmol), the appropriate 2-amino-
pyrimidine, 2-aminopyridine, 3-amino-5-phenylpyrazole, 3-
amino-4-methyl-5-phenylpyrazole, 2-amino-4-phenylthiazole,
o-phenylenediamine, 2-aminothiophenol, 2-aminophenol or
2,3-diaminopyridine (6 mmol), and triethylamine (0.5 g, 0.75
mL, 5 mmol) in ethanol (25 mL) was heated under reflux for
3 h and then cooled. The solid precipitated was collected,
washed with water, and then crystallized from the appropriate
solvent to give 3(a, b), 5, 6(a, b), 7, 8, 11–13, respectively.
3-Phenylazo-2-(4-methyl-2-phenylthiazol-5-yl)imidazo[1,2-a]
pyrimidine (3a). This compound was obtained as violet crys-
tals (DMF-EtOH), mp > 300ꢁC, yield (69%); IR (cmꢀ1):
1
3060, 2923 (CH), 1623 (C¼¼N), 1599 (C¼¼C), 1321 (CH3). H-
NMR (CD3)2SO: d ¼ 2.46 (s, 3H, 4-methylthiazole), 7.07–
7.13 (t, 3H, J ¼ 5.6 Hz, pyrimidine H-5), 7.49–7.51 (d, 2H,
J ¼ 4.0 Hz, ArH), 7.94–7.97 (m, 3H, ArH), 8.27 (m, 3H,
ArH), 8.56–8.58 (d, 1H, J ¼ 4.0 Hz, pyrimidine H-4), 8.95–
As shown in Table 1, there is variability in the sus-
ceptibilities of the different organisms to the different
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March 2010 Reactions with Hydrazonoyl Halides 62: Synthesis and Antimicrobial Evaluation of Some New
Imidazo[1,2-a]pyrimidine, Imidazo[1,2-a]pyridine, Imdazo[1,2-b]pyrazole, and Quinoxaline Derivatives
481
8.98 (d, 1H, J ¼ 4.0 Hz, pyrimidine H-6). 13C-NMR: d ¼
3-(4-Methyl-2-phenylthiazol-5-yl)-2-phenylazo-(1H)-quino-
xaline (9). This compound was obtained as orange crystals
(EtOH), mp 240–42ꢁC, yield (80%); IR (cmꢀ1): 3399 (NH),
3047, 2964 (CH), 1632 (C¼¼N), 1605 (C¼¼C). 1H-NMR: d ¼
2.57 (s, 3H, 4-methylthiazole), 7.08–7.89 (m, 14H, ArH), 8.92
(s, br., 1H, NH), 9.22 (s, br., 1H, NH). Anal. Calcd. for
C24H19N5S (409.51): C, 70.93; H, 4.68; N, 17.10; S, 7.83.
Found: C, 70.50; H, 4.56; N, 17.39; S, 7.70.
14.71 (CH3), 110.64, 156.19, 160.11 (thiazole), 113.45,
120.45, 145.78 (imidazole), 122.04, 125.11, 127.31, 129.21,
130.12, 131.18, 135.20, 154.68 (aromatic carbons), 108.12,
134.45, 152.67 (pyrimidine). Anal. Calcd. for C22H16N6S
(396.46): C, 66.72; H, 4.07; N, 21.20; S, 8.09. Found: C,
66.60; H, 4.00; N, 21.40; S, 8.20.
3-[4-Methylphenylazo)-2-(4-methyl-2-phenylthiazol-5-yl)imidazo
[1,2-a]pyrimidine (3b). This compound was obtained as red
crystals (AcOH), mp 272–74ꢁC, yield (66%); IR (cmꢀ1): 3060,
3-(4-Methyl-2-phenyl-thiazol-5-yl)-2-phenylhydrazinobenzo
[1,4]thiazine (11). This compound was obtained as shiny green
crystals (DMF/EtOH), mp 280–82ꢁC, yield (89%); IR: 3422
1
2968 (CH), 1625 (C¼¼N), 1599 (C¼¼C), 1321 (CH3). H-NMR
1
(CD3)2SO: d ¼ 2.46 (s, 3H, 4-methylthiazole), 2.53 (s, 3H, 4-
CH3C6H4), 6.86–6.70 (t, 3H, pyrimidine H-5), 7.36–7.37 (d,
2H, ArH), 7.62–7.67 (m, 3H, ArH), 7.70–7.81 (m, 2H, ArH),
8.53–8.54 (d, 1H, pyrimidine H-4), 8.65–8.66 (d, 1H, pyrimi-
dine H-6). Anal. Calcd. for C23H18N6S (410.49): C, 67.30; H,
4.42; N, 20.47; S, 7.81. Found: C, 67.55; H, 4.53; N, 20.12; S,
7.68.
(NH), 3058, 2982 (CH), 1655 (C¼¼N), 1602 (C¼¼C). H-NMR:
d ¼ 2.62 (s, 3H, 4-methylthiazole), 7.18–8.29 (m, 14H, ArH),
13.09 (s, br., 1H, NH). MS: 426 (4.98%), 384 (11%), 360 (16%),
354 (59%), 319 (17.8%), 302 (38%), 372 (18%), 270 (100%), 226
(15%), 212 (22%), 196 (12%), 148 (54.9%), 122 (27%), 94
(23%), 63 (20%). Anal. Calcd. for C24H18N4S2 (426.56): C,
67.58; H, 4.25; N, 13.13; S, 15.03. Found: C, 67.90; H, 4.55; N,
13.33; S, 15.21.
2-(4-Methyl-2-phenyl-1,3-thiazol-5-yl)-3-phenylazoimidazo
[1,2-a]pyridine (5). This compound was obtained as violet
crystals (DMF/EtOH), mp 223–26ꢁC, yield (55%); 1H-NMR
(CD3)2SO: d ¼ 2.46 (s, 3H, 4-methylthiazole), 6.85 (t, 1H,
pyridine H-5), 7.15 (d, 1H, pyridine H-3), 7.37 (t, 1H, pyridine
H-4), 7.62–7.84 (m, 10 H, ArH), 8.78 (d, 1H, pyridine H-6).
13C-NMR: d ¼ 14.85 (CH3), 111.21, 155.71, 160.32 (thiazole),
111.62, 121.45, 144.10 (imidazole), 122.10, 125.00, 126.58,
128.84, 130.54, 131.10, 136.24, 154.44 (aromatic carbon),
112.12, 117.89, 123.77, 126.28 (pyridine). Anal. Calcd. for
C23H17N5S (395.48): C, 69.85; H, 4.33; N, 17.71; S, 8.11.
Found: C, 69.70; H, 4.09; N, 17.55; S, 8.00.
3-(4-Methyl-2-phenyl-thiazol-5-yl)-2-phenylhydrazinobenzo
[1,4]oxazine (12). This compound was obtained as yellow crys-
tals (DMF/EtOH), mp 202–204ꢁC, yield (72%); IR (cmꢀ1):
3422 (NH), 2924 (CH), 1634 (C¼¼N), 1602 (C¼¼C). 1H-NMR:
d ¼ 2.59 (s, 3H, 4-methylthiazole), 7.18–8.29 (m, 14H, ArH),
9.32 (s, br., 1H, NH). 13C-NMR: d ¼ 15.57 (CH3), 112.32,
158.85, 162.10 (thiazole), 129.23, 139.53, 144.71, 150.82 (oxa-
zine), 115.24, 118.35, 119.85, 127.45, 128.68, 129.28, 130.30,
130.45, 13.90, 133.72, 143.68 (aromatic carbons). Anal. Calcd.
for C24H18N4OS (410.49): C, 70.22; H, 4.42; N, 13.56; S, 7.81.
Found: C, 70.44; H, 4.56; N, 13.72; S, 7.65.
3-(4-Methyl-2-phenyl-thiazol-5-yl)-2-phenylhydrazino-1H-pyrido
[2,3-b]pyrazine (13). This compound was obtained as red crys-
tals (DMF/EtOH), mp > 300ꢁC, yield (70%); IR (cmꢀ1): 3382
3-Phenylazo-2-(4-methyl-2-phenylthiazol-5-yl)-6-phenyl-5H-
imidazo[1,2-b]pyrazole (6a). This compound was obtained as
red crystals (DMF/EtOH), mp > 300ꢁC, yield (89%); IR
1
(NH), 3060, 2969 (CH), 1632 (C¼¼N), 1595 (C¼¼C). H-NMR:
1
(cmꢀ1): 3424 (NH), 1633 (C¼¼N), 1607 (C¼¼C). H-NMR: d ¼
d ¼ 2.56 (s, 3H, 4-methylthiazole), 7.18–8.35 (m, 13H, ArH),
10.51 (s, br., 2H, NH). MS: 409 (4.9%), 308 (22.8%), 228
(10.5%), 213 (22.4%), 205 (17.8%), 183 (16%), 182 (100%),
179 (14.6%), 153 (16.5%), 140 (77%), 125 (14%), 124 (20%).
Anal. Calcd. for C23H18N6S (410.49): C, 67.30; H, 4.42; N,
20.47; S, 7.81. Found: C, 67.11; H, 4.10; N, 120.12; S, 7.55.
General procedure for the synthesis of 4 and 8. A mix-
ture of 2-bromo-1-(4-methyl-2-phenyl-1,3-thiazol-5-yl)ethanone
[20] (1.48 g, 5 mmol) and 2-aminopyrimidine (0.48 g, 6 mmol)
or 2-amino-4-phenylthiazole (0.56 g, 6 mmol) in ethanol (25
mL) was heated under reflux for 3–4 h. The resulting solid was
neutralized with sodium bicarbonate solution, collected by filtra-
tion, and then was crystallized from ethanol to give 4 and 8,
respectively.
2.46 (s, 3H, 4-methylthiazole), 6.19 (s, 1H, pyrazole H-4),
7.36–7.91 (m, 16 H, ArH and NH proton). Anal. Calcd. for
C27H20N6S (460.55): C, 70.41; H, 4.38; N, 18.25; S, 6.96.
Found: C, 70.40; H, 4.02; N, 18.41; S, 7.02.
2-(4-Methyl-2-phenyl-thiazol-5-yl)-5-methyl-6-phenyl-3-phe-
nylazo-5H-imidazo[1,2-b]pyrazole (6b). This compound was
obtained as red crystals (DMF/EtOH), mp > 300ꢁC, yield
1
(67%); H-NMR: d ¼ 2.46 (s, 3H, 4-methylthiazole), 2.50 (s,
3H, 4-CH3C6H4), 6.15 (s, 1H, pyrazole H-4), 7.36–8.10 (m,
14H, ArH), 8.42 (s, br., 1H, NH). 13C-NMR: d ¼ 14.45 (CH3),
21.21 (CH3), 83.89, 142.67, 159.14 (pyrazole), 108.00, 122.45
(imidazole, 114.23, 160.45, 163.57 (thiazole), 122.12, 122.57,
128.42, 129.23, 130.12, 134.45, 139.57, 153.38 (aromatic car-
bons). Anal. Calcd. for C28H22N6S (474.58): C, 70.86; H,
4.67; N, 17.71; S, 6.76. Found: C, 71.14; H, 4.73; N, 17.66; S,
6.66.
2-(4-Methyl-2-phenylthiazol-5-yl)imidazo[1,2-a]pyrimidine
(4). This compound was obtained as yellow crystals (EtOH),
mp 223–26ꢁC, yield (62%); IR (cmꢀ1): 3060.3, 2928 (CH),
1655 (C¼¼N), 1599 (C¼¼C), 1369 (CH3). 1H-NMR: d ¼ 2.46
(s, 3H, 4-methylthiazole), 6.91 (d, 1H, pyrimidine H-5), 7.62
(t, 2H, ArH), 7.68 (t, 1H, ArH), 7.76 (d, 2H, ArH), 7.91 (s,
1H, imidazole H-4), 8.50 (d, 1H, pyrimidine H-6), 8.57 (d, 1H,
pyrimidine H-4). 13C-NMR: d ¼ 13.85 (CH3), 114.21, 150.71,
160.82 (thiazole), 111.62, 124.45, 149.10 (imidazole), 125.00,
126.58, 131.10, 136.24 (phenyl), 110.12, 135.77, 151.28 (py-
rimidine). MS: 293 (8.8%), 292 (30%), 202 (19.9%), 203
(10%), 188 (22.9), 144 (15.9), 92 (7.1%), 66 (10.6%). Anal.
Calcd. for C16H12N4S (292.36): C, 65.73; H, 4.14; N, 19.16;
S, 10.97. Found: C, 65.90; H, 4.33; N, 19.02; S, 10.70.
6-(4-Methyl-2-phenyl-thiazol-5-yl)-5-phenylazo3-phenylimi-
dazo[2,1-b]thiazole (7). This compound was obtained as red
crystals (AcOH), mp > 300ꢁC, yield (80%); 1H-NMR: d ¼
2.46 (s, 3H, 4-methylthiazole), 7.24 (s, 1H, thiazole H-5),
7.36–7.97 (m, 15H, ArH), 13C-NMR: d ¼ 13.57 (CH3), 14.57
(CH3), 103.25, 111.23, 126.32, 158.74, 159.62, 145.43 (thia-
zole rings), 114.25, 120.85 (imidazole), 122.12, 125.42,
127.61, 128.08, 130.24, 131.75, 135.28, 155.35 (aromatic car-
bons). Anal. Calcd. for C27H19N5S2 (477.60): C, 67.90; H,
4.01; N, 14.66; S, 13.43. Found: C, 67.80; H, 4.96; N, 14.30;
S, 13.07.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

482
A. O. Abdelhamid, E. K. A. Abdelall, and Y. H. Zaki
Vol 47
[2] Rateb, N. M.; Abdelhamid, A. O. Heteroat Chem 2004, 15,
[3] Abdelhamid, A. O.; Sayed, A. R.; Zaki, Y. H. Phosphorus
2-(4-Methyl-2-phenylthiazol-5-yl)-6-phenyl-1H-imidazo[1,2-
107.
b]pyrazole (8). This compound was obtained as orange crystals
(DMF), mp 244–47ꢁC, yield (60%); 1H-NMR (CD3)2SO: d ¼
2.46 (s, 3H, 4-methylthiazole), 6.15 (s, 1H, pyrazole H-4), 7.40 (s,
1H, imidazole H-4), 7.45–7.92 (m, 10H, ArH), 8.42 (s, br., 1H,
NH). Anal. Calcd. for C21H16N4S (356.44): C, 70.67; H, 4.52; N,
15.72; S, 9.00. Found: C, 70.55; H, 4.31; N, 15.50; S, 9.07.
Sulfur Silicon Relat Elem 2007, 182, 1447.
[4] Abdelhamid, A. O.; Ismail, Z. H.; Abdel-Aziem, A. J Chem
Res 2007, 609.
[5] Shawali, A. S.; Edrees, M. M. Arkivoc 2006, 9, 292.
[6] Shawali, A. S.; Mosselhi, M. A. N. J Heterocycl Chem
2003, 40, 725.
Alternative synthesis of 3a, b and 6a. A solution of the
appropriate arenediazonium chloride (10 mmol) was added
dropwise to a stirred solution of the appropriate reactant (4, 8)
(10 mmol) in ethanol (50 mL) containing sodium acetate trihy-
drate (1.3g, 10 mmol) at 0–5ꢁC. The reaction mixture was
stirred for 3 h at 0ꢁC, the resulting solid was collected and
crystallized from ethanol to give 3(a, b) and 6a, respectively.
3-(4-Methyl-2-phenyl-thiazol-5-yl)-2-phenylazoquinoxaline
(10). A mixture of compound 9 (0.5 g) in ethanol (20 mL) and
hydrogen peroxide (3 mL, 30%) was stirred at room temperature
for 24 h. The solvent was evaporated under reduced pressure,
the resulting solid was collected and recrystallized to give 10.
This compound was obtained as red crystals (DMF/EtOH), mp
[7] Abdelhamid, A. O.; El-Ghandour, A. H.; Hussein, A. M.;
Zaki, Y. H. J Sulfur Chem 2004, 25, 329.
[8] Abdelhamid, A. O.; Alkhodshi, M. A. M. J Heterocycl
Chem 2005, 42, 527.
[9] Abdelhamid, A. O.; Al-Atoom, A. A. Synth Commun 2006,
36, 97.
[10] Nussbaumer, P.; Petranyi, G., Stutz, A. J Med Chem 1991,
34, 65.
[11] Broom, N. J. P.; Elder, J. S.; Hannan, P. C. T.; Pons, J. E.;
O’Hanlon, P. J.; Walker, G.; Wilson, J.; Woodall, P. J. J Antibiot
1995, 48, 1336.
[12] Nakanishi, M.; Imamura, H.; Maruyama, Y.; Hoshino, H. J
Pharm Soc Jpn 1970, 90, 272.
1
> 300ꢁC, yield (78%); H-NMR (CD3)2SO: d ¼ 2.46 (s, 3H, 4-
methylthiazole), 7.26–8.13 (m, 14H, ArH). 13C-NMR: d ¼
15.57 (CH3), 109.58, 162.11, 167.00 (thiazole), 138.32, 139.54,
146.61, 145.45 (pyrazine), 124.12, 125.54, 126.28, 129.23,
129.65, 129.89, 132.52, 133.21, 154.94 (phenyl groups). Anal.
Calcd. for C24H117N5S (407.49): C, 70.74; H, 4.21; N, 17.19; S,
7.87. Found: C, 70.90; H, 4.31; N, 17.33; S, 7.60.
[13] Briel, D. Pharmazie 1955, 50, 675.
[14] Yamaguchi, M.; Maruyama, N.; Koga, T.; Kamei, K.;
Akima, M.; Kuroki, M.; Hamana, M.; Ohi, N. Chem Pharm Bull 1995,
43, 236.
[15] Boyd, R. E.; Press, J. P.; Rasmussen, C. R.; Raffa, R. B.;
Codd, E. E.; Connelly, C. D.; Martinez, Q. S.; Li, R. P.; Lewis, M.
A.; Almond, B. J. J Med Chem 2001, 44, 863.
[16] Shawali, A. S.; Harb, N. M. S.; Badahdah, K. O. J Hetero-
cycl Chem 1985, 22, 1397.
Acknowledgment. The authors are very grateful to Professor
M.A. Amin, Dean, Head Department of Microbiology, Faculty of
Pharmacy, Beni-Suef University, for his kind supervision to the
antimicrobial evaluation.
[17] Shawali, A. S.; Mosselhi, M. A. M.; Farghaly, T. A. J
Chem Res 2007, 479.
[18] El-Helby, A. A. J Pharm Sci 2001, 27, 375.
[19] Abdelhamid, A. O.; Abed, N. M.; Al-Fayez, F. M. Phospho-
rus Sulfur Silicon Relat Elem 2000, 156, 35.
[20] Prakash, O.; Tyagi, D. S.; Sangal, D. S. J Indian Chem Soc
1981, 57, 1136.
REFERENCES AND NOTES
[1] Abdelhamid, A. O.; Afif, M. A. Phosphorus Sulfur Silicon
Relat Elem, Part 61 2008, 183, 2703.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet