Synthesis and reactions of 2-chloro-2-(hydroximino)-1-(4-methyl-2- phenylthiazol-5-yl)ethanone

Article abstract of DOI:10.1002/jhet.5570430202

3-Nitrosoimidazo[1,2-a]pyridine, 3-nitrosoimidazo[1,2-a]pyrimidine, 3-nitrosoquinoxaline, 2-nitroso-4H-benzo[b]thiazine, 2-nitroso-4H-benzo[b] oxazine, isoxazoles, isoxazolo[3,4-d]pyridazines and pyrrolo[3,4-d]isoxazole-4, 6-dione were synthesized from 2-

Full text of DOI:10.1002/jhet.5570430202

Mar-Apr 2006
249
Synthesis and Reactions of 2-Chloro-2-(hydroximino)-1-(4-methyl-2-
phenylthiazol-5-yl)ethanone
Abdou O. Abdelhamid , Ahmed H. Elghandour , Sayed A. Ahmed and Yasser H. Zaki
a
b
b
b
a
Department of Chemistry, Faculty of Science, Cairo University, Giza 12316, Egypt.
b
Department of Chemistry, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt.
Abdou_abdelhamid@yahoo.com
Received April 4, 2005
3-Nitrosoimidazo[1,2-a]pyridine, 3-nitrosoimidazo[1,2-a]pyrimidine, 3-nitrosoquinoxaline, 2-
nitroso-4H-benzo[b]thiazine, 2-nitroso-4H-benzo[b]oxazine, isoxazoles, isoxazolo[3,4-d]pyridazines and
pyrrolo[3,4-d]isoxazole-4,6-dione were synthesized from 2-chloro-2-(hydroximino)-1-(4-methyl-2-
phenylthiazol-5-yl)ethanone and different reagents. Structures of the newly synthesized compounds were
confirmed by elemental analysis and spectral data.
J. Heterocyclic Chem., 43, 249 (2006).
Introduction.
spectrum of the reaction product is not observed. Structure
4 seems unlikely because 2-aminopyridine was reacted
with 2-bromo-1-(4-methyl-2-phenyl-1,3-thiazol-5-
yl)ethanone to give 2-(4-methyl-2-phenyl-1,3-thiazol-5-
yl)imidazo[1,2-a]pyridine (6) which reacted with nitrous
acid to afford a product identical in all respects (mp, mixed
Hydroximoyl halides have been widely used for the syn-
thesis of heterocyclic compounds [1-5]. Isoxazoles are
widely investigated for therapentic uses, especially as tran-
quilizing agents, CNS regulants and are reported to have
bacteriostatic, bactericida, antitrypanosomal activity in
vitro and fungicidal activities [5,6]. In conjunction with
our previous work [7-14], we report here the synthesis of
several derivatives of imidazo[1,2-a]pyridines, imi-
dazo[1,2-a]pyrimidines, isoxazoles, isoxazolo[3,4-d]pyri-
dazines, and pyrrolo[3,4-d]isoxazole-4,6-dione required
for biological screening.
1
mp., and spectra) with 3a. The H NMR spectrum of 3a
showed signals at δ = 2.49 (s, 3H), 7.52-7.64 (m, 8H) and
-1
9.75 (d, 1H). Its IR spectrum revealed a band at 1542 cm
due to the nitroso group. Based on these data 2-(4-methyl-
2-phenyl-1,3-thiazol-5-yl)-3-nitrosoimidazo[1,2-a]pyri-
dine (3a) was taken to be the reaction product.
Similarly, 2 was reacted with each 2-amino-3-methylpyri-
dine, and 2-aminopyrimidine to afford 6-methyl-2-(4-
methyl-2-phenyl-1,3-thiazol-5-yl)-3-nitrosoimidazo[1,2-
a]pyridine 3b and 2-(4-methyl-2-phenyl-1,3-thiazol-5-yl)-3-
nitrosoimidazo[1,2-c]pyrimidine 7, respectively (Figure 1).
Compound 2 was reacted with o-phenylenediamine in
ethanol to give a single product (according to tlc). On the
basis of their spectral and elemental analyses, the products
were assigned as: 1,4-dihydro-2-(4-methyl-2-phenylthia-
zol-5-yl)-3-nitrosoquinoxaline (8a). IR spectra revealed no
Results and Discussion.
Nitrosation of 1-(4-methyl-2-phenylthiazol-5-yl)-2-oxo-
dimethylsulfonium bromide (1) [15] in dioxan-water solu-
tion in the presence of hydrochloric acid gave 2-chloro-2-
(hydroximino)-1-(4-methyl-2-phenylthiazol-5-yl)ethanone
(2). Structure 2 was confirmed on the basis of elemental
analysis, spectral data and chemical transformations. Thus,
1
the H NMR spectrum showed signals at δ = 2.47 (s, 3H),
7.19-7.48 (m, 5H) and 13.12 (s, 1H). Its IR spectrum
revealed bands at 3400 (OH) and 1645 (CO conjugated).
Treatment of 2 with 2-aminopyridine in ethanol afforded
-1
absorption band between 1650-1800 cm due the absence
of CO group but showed an absorption band at 1547 for the
nitroso group. Compound 8a was readily oxidized to 2-(4-
methyl-2-phenyl-1,3-thiazol-5-yl)-3-nitrosoquinoxaline
(10) via hydrogen peroxide in acetic solution. Based on the
foregoing results the isomeric structure 9 was ruled out.
a product that has the molecular formula C H N OS of
17 12
4
which structures 3-5 seemed possible (Figure 1). Structure
5 was eliminated because an absorption band in the region
-1
1650-1800 cm corresponding to a CO group in the IR

250
A. O. Abdelhamid, A. H. Elghandour, S. A. Ahmed and Y. H. Zaki
Vol. 43
Similarly, treatment of 2 with each of 2-aminothiophe-
according to tlc, whose structure 15a or isomer 16a
(Figure 2). Formation of 15 can be explained via reaction
of nitrile oxide, which formed in situ from hydroximoyl
chloride 12a and triethylamine, with 11 in the presence of
triethylamine to afford cycloadduct intermediate 13a or
14a, and spontaneously dimethylamine elimination to give
isoxazole 15a or isoxazole 16a. Structure of 15 was eluci-
dated by elemental analysis, spectral data and chemical
nol and 2-aminophenol gave 3-(4-methyl-2-phenylthiazol-
5-yl)-2-nitroso-4H-benzo[b]thiazine (8b), 3-(4-methyl-2-
phenylthiazol-5-yl)-2-nitroso-4H-benzo[b]oxazine (8c),
respectively (Tables 2 and 3).
Treatment of 3-(dimethylamino)-1-(4-methyl-2-
phenyl(1,3-thiazol-5-yl))prop-2-ene-1-one (11) [16] with
hydroximoyl chloride 12a in toluene containing triethy-
lamine at room temperature afforded one isolable product,
1
transformations. H NMR spectra of 15a showed signals at

Mar-Apr 2006
2-Chloro-2-(hydroximino)-1-(4-methyl-2-phenylthiazol-5-yl)ethanone
251
Finally, treatment of 2 with the appropriate N-aryl-
malemides 21a-c [18] in boiling toluene gave 3-[(4-methyl-
2-phenyl-1,3-thiazol-5-yl)carbonyl]-5-substituted-3aH-
pyrrolo[3,4-d]isoxazole-4,6(5H,6aH)-dione 22a-c, respec-
tively (Figure 3). Structure 22 was confirmed by elemental
analysis and spectral data. The IR spectra of 22a-c raveled
δ = 2.73 (s, 3H), 7.26-7.64 (m, 8H), 7.97-7.98 (d, 1H),
8.08-8.12 (d, 1H) and 9.00 (s, 1H). Its IR spectrum
revealed bands at 3047, 2920 (CH), 1674 (CO) and 1594
(C=C). Thus, compound 15a reacted with hydrazine
hydrate in boiling ethanol to give 4-(4-methyl-2-phenyl-
1,3-thiazol-5-yl)-7-phenylisoxazolo[3,4-d]pyridazine
(17a) (Figure 2).
Similarly, 11 was reacted with the appropriate hydroxi-
moyl chlorides 12b-e to afford 4-[(4-methyl-2-phenylthia-
zol-5-carbonyl)-isoxazol-3-yl]-substituted methanone
derivatives 15b-e, which converted to 4-(4-methyl-2-
phenyl-1,3-thiazol-5-yl)-7-substituted isoxazolo[3,4-d]-
pyridazine derivatives 17b-e, respectively.
-1
bands near at 1720 and 1635 cm due to CO and -CO-NAr-
1
CO- groups [18]. H NMR spectrum of 22a showed signals
at δ = 2.86 (s, 3H), 5.13-5.14 (d, 1H), 5.71-5.75 (d, 1H), 6.92-
7.27 (m, 6H), 7.43-7.48 (d, 2H) and 8.01-8.05 (d, 2H).
Treatment of acrylonitrile with 2 in boiling toluene
afforded one isolable product, according to tlc, which struc-
1
tures 18 and 19 seemed possible (Figure 3). H NMR spec-
trum of the product showed signals at δ = 2.79 (s, 3H), 2.93-
2.97 (d, 2H, J = 10 Hz, isoxazoline C-4), 3.75 (t, 1H, J = 10
Hz, isoxazoline C-5), 7.40-7.89 (m, 3H) and 7.89-8.12 (m,
2H). Its IR spectrum revealed bands at 1660 (CO) but no
-1
absorption at 2200 cm for CN group, which supports the 5-
cyano structure (19) [17]. Furthermore, the product was read-
ily hydrolysed by sulfuric acid to give the corresponding
amide 20 (IR spectral bands at 3330, 3180 (NH ) and 1690
2
(CO)). Also, treatment of 2 with acryloamide in boiling
toluene afforded product identical with 20. Hence structure
18 was eliminated and the product was assigned to have the
structure formulated as 3-[(4-methyl-2-phenyl-1,3-thiazol-5-
yl)carbonyl]-4,5-dihydroisoxazole-5-carbonitrile (19).
Antimicrobial Activity.
The tested microorganism was gram +ve bacteria, gram
-ve bacteria and some Fungal-plant. Sensitivity of the
Table 1
Response of various microorganisms to some synthesized compounds in vitro (culture).
Microorganism/ Staphylococcus
Streptococcus
faecalis (G )
Bacillus
subtilis
(G )
Echerichia
coli (G )
Aspergills
flvus
(Fungus)
0.0 / 0.0
Candida
albicans
(Fungus)
20 / 37
+
+
-
Compound no
albus (G )
+
Ampicillin /
Tetracycline
34R / 27
37 / 31
33 / 30
39 / 34
2
3a
3b
8a
8b
8c
15b
15c
15d
15e
17d
17e
19
8
5
10
3
10
8
12
3
15
12
16
10
19
13
13
12
13
12
14
0.0
2
10
0.0
14
2
15
13
22
20
19
17
29
22
25
8
11
0.0
13
8
9
9
17
13
15
2
21
21
30
26
28
11
9
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
16
10
20
8
25
11
10
0.0
14
13
17
8
17
16
23
22
23
10
8
10
10
11
10
10
10
14
16
13
16
23
8
20
22a
22b
22c
25
10
St. Reference standerd; Ampicillin and tetracycline were used as standard antibacterial agent and antifungal agents. Values
show zone of inhibition in mm. Diameter of the inhibition zones were: high (11-15 mm), moderate (6-10 mm), slight (1-5
mm), negative (0)

252
A. O. Abdelhamid, A. H. Elghandour, S. A. Ahmed and Y. H. Zaki
Vol. 43
Table 2
Characterization Data of the Newly Synthesized Compounds
Compd
No.
M.P., °C
Solvent
Color
Yield %
Mol. Formula
mol.wt
% Analyses calcd./found
H
C
N
S
192-93
EtOH
Yellow
78
C12 H9 Cl N2 O2 S
280.73
51.34
51.33
63.73
63.71
64.65
64.62
70.08
70.10
59.80
59.77
64.65
64.62
61.51
61.49
64.46
64.44
65.04
65.07
67.37
67.35
62.63
62.65
59.98
60.00
70.74
70.71
63.68
63.71
68.09
68.13
63.32
63.33
60.62
60.59
71.41
71.44
64.22
64.25
60.59
60.61
57.13
57.14
63.30
63.28
64.03
63.99
61.74
61.77
3.23
3.26
3.78
3.80
4.22
4.19
4.50
4.52
3.45
3.44
4.22
4.20
3.73
3.77
3.91
3.90
3.64
3.66
3.77
3.80
3.32
3.29
3.18
3.15
3.80
3.82
3.63
3.66
3.81
3.85
3.36
3.39
3.21
3.22
3.84
3.85
3.66
3.63
3.73
3.74
4.16
4.19
3.62
3.65
3.97
3.97
3.83
3.81
9.98
10.00
17.49
17.52
16.75
16.77
14.42
14.39
21.79
21.83
16.75
16.74
11.96
12.00
12.53
12.55
16.86
16.85
7.48
11.42
11.38
10.01
9.99
2
233-35
Dioxan
228-29
Dioxan
98-101
Dioxan
240-42
Dioxan
226-28
Dioxan
263-65
Dioxan
198-200
Dioxan
> 300
Yellow
89
C17 H12 N4 O S
320.37
3a
Yellow
87
C18 H14 N4 O S
334.39
9.59
9.57
3b
Yellow
80
C17 H13 N3 S
291.37
11.01
10.98
9.98
6
Yellow
90
C16 H11 N5 O S
321.35
7
10.00
9.59
Yellow
85
C18 H14 N4 O S
334.39
8a
9.62
Yellow
81
C18 H13 N3 O S2
351.44
18.25
18.22
9.56
8b
Yellow
88
C18 H13 N3 O2 S
335.38
8c
9.56
Yellow
64
C18 H12 N4 O S
332.38
9.65
9.64
10
Dioxan
155-58
EtOH
Pale Brown
75
C21 H14 N2 O3 S
374.41
8.56
8.55
15a
15b
15c
15d
15e
17a
17b
17c
17d
17e
19
7.44
159-61
EtOH
Pale Brown
78
C19 H12 N2 O4 S
364.37
7.69
8.80
7.71
7.36
8.83
168-70
EtOH
Yellow
83
C19 H12 N2 O3 S2
380.44
16.86
16.90
7.55
7.35
6.60
173-75
EtOH
Yellow
80
C25 H16 N2 O3 S
424.47
6.59
8.91
7.53
167-69
EtOH
Yellow
81
C25 H17 N3 O3 S2
471.55
13.60
13.55
8.66
8.88
206-208
Dioxan
215-17
Dioxan
222-15
Dioxan
232-35
Dioxan
221-23
Dioxan
109-112
EtOH
Yellow
77
C21 H14 N4 O S
370.42
15.12
15.15
15.55
15.51
14.88
14.91
13.32
13.35
14.98
15.00
14.13
14.11
13.33
13.30
10.07
10.10
9.74
8.69
Yellow
79
C19 H12 N4 O2 S
360.39
8.90
8.88
Yellow
80
C19 H12 N4 O S2
376.45
17.04
17.00
7.63
Yellow
73
C25 H16 N4 O S
420.48
7.66
Yellow
76
C25 H17 N5 O S2
467.56
13.72
13.74
10.78
10.80
10.17
10.19
7.68
Pale Yellow
71
C15 H11 N3 O2 S
297.33
200-202
EtOH
Pale Yellow
66
C15 H13 N3 O3 S
315.34
20
199-201
EtOH
Yellow
85
C22 H15 N3 O4 S
417.43
22a
22b
22c
7.65
202-204
EtOH
Yellow
84
C23 H17 N3 O4 S
431.46
7.43
9.72
9.39
7.40
7.17
195-97
EtOH
Yellow
82
C23 H17 N3 O5 S
447.46
9.42
7.14
EXPERIMENTAL
selected microorganisms to some synthesized compounds
were determined in vitro culture that were dissolved in
chloroform, the tests were carried out using the filter paper
and hole plate method [19]. Studies on the biological activ-
ity of compounds in comparison with Ampicillin and tetra-
cycline are shown in Table 1. In general all tested com-
pounds were capable of inhibiting the growth of gram pos-
itive and gram negative.
All melting points were determined on an electrothermal appa-
ratus and are uncorrected. IR spectra were recorded (KBr discs)
on a Shimadzu FT-IR 8201 PC spectrophotometer. H NMR
1
spectra were recorded in CDCl and (CD ) SO solutions on a
3
3 2
Varian Gemini 300 MHz spectrometer and chemical shifts are
expressed in δ units using TMS as an internal reference. Mass
spectra were recorded on a GC-MS QP1000 EX Shimadzu.

Mar-Apr 2006
2-Chloro-2-(hydroximino)-1-(4-methyl-2-phenylthiazol-5-yl)ethanone
253
Table 3
Spectra of Synthesized Compounds
Comp. No.
Spectral data
2
IR: 3420 (OH), 3074, 2954 (CH)
1H NMR: 2.49 (s, 3H), 7.52-7.64 (m, 8H) and 9.75 (d, 1H).
IR: 3062, 2950 (CH), 1624 (C=N) and 1542 (NO).
3a
1H NMR: 2.71 (s, 3H), 3.12 (s, 3H), 7.11-7.64 (m, 7H) and 9.72-9.75 (d, 1H).
3b
7
IR: 3050, 2920 (CH), 1614 (C=N) and 1539 (NO).
1H NMR: 2.18 (s, 3H), 7.25-7.54 (m, 4H), 8.18-8.20 (m, 2H), 8.97 (d, 1H), and 9.98 (d, 1H).
IR: 3112, 3066 (CH), 1647 (C=N), 1604 (C=C) and 1533 (NO).
1H NMR: 2.74 (s, 3H), 6.85-7.30 (m, 6H), 7.78-7.85 (m, 3H), 9.05 (s, br., 1H), and 10.08 (s, br., 1H).
IR: 3398 (NH), 3047, 2920 (CH), 1635 (C=N), 1604 (C=C) and 1477 (NO).
1H NMR: 2.51 (s, 3H), 7.37-7.55 (m, 8H), 7.95-7.99 (m, 1H) and 13.01 (s, br., 1H).
IR: 33421 (NH), 3047, 2920 (CH), 1643 (C=N), 1604 (C=C) and 1562 (NO).
MS: 351 (8.6%, M+), 336 (17.9%), 335 (32.9%), 333 (100%), 308 (66.8%), 301 (23.2), 2.05 (67.3%), 160 (23.9%), 104
(11.6%), 71 (28.8%), 70 (17.3%).
1H NMR: 2.98 (s, 3H), 7.34-7.52 (m, 5H), 7.71-7.74 (m, 1H), 7.96-8.01 (dd, 1H), 8.11-8.16 (m, 2H) and 13.01 (s, br., 1H).
IR: 3413 (NH), 3047, 2920 (CH), 1635 (C=N), 1616 (C=C) and 1535 (NO).
MS: 320 (46.3%, M-CH3), 292 (25.8%), 202 (80%), 174 (33.7%), 104 (17.9%), 71 (100%).
1H NMR: 2.74 (s, 3H), 6.85-7.30 (m, 6H) and 7.78-7.85 (m, 3H)
8a
8b
8c
10
IR: 3047, 2920 (CH), 1635 (C=N), 1604 (C=C) and 1477 (NO).
1H NMR: 2.73 (s, 3H), 7.26-7.64 (m, 8H), 7.97-7.98 (d, 1H), 8.08-8.12 (d, 1H) and 9.00 (s, 1H)
IR: 3047, 2920 (CH), 1674 (CO) and 1594 (C=C).
1H NMR: 2.64 (s, 3H), 6.86-6.87 (d, 1H), 7.58-7.70 (m, 4H), 8.02-8.05 (m, 2H), 9.25 (s, 1H) and 9.96 (s, 1H)
IR: 3047, 2920 (CH), 1663, 1636 (CO’s) and 1594 (C=C).
1H NMR: 2.63 (s, 3H), 7.34-7.38 (t, 1H), 7.55-7.58 (m, 3H), 8.01-8.05 (m, 3H), 8.30-8.32 (d, 1H) and 9.96 (s, 1H)
15a
15b
15c
15d
15e
17a
19
IR: 3047, 2920 (CH), 1636 (CO) and 1561 (C=C).
1H NMR: 2.68 (s, 3H), 7.55-7.93 (m, 5H), 7.96-8.19 (m, 6H), 8.63 (s, 1H), and 10.12 (s, 1H)
IR: 3047, 2920 (CH), 1666, 1635 (CO) and 1590 (C=C).
1H NMR: 2.73 (s, 3H), 2.78 (s, 3H), 7.26-9.05 (m, 10H) and 8.94 (s, 1H)
IR: 3047, 2920 (CH), 1635 (CO) and 1585 (C=C).
1H NMR: 2.73 (s, 3H), 7.26-7.64 (m, 8H), 7.97-7.98 (d, 1H), 8.08-8.12 (d, 1H) and 9.00 (s, 1H)
IR: 3047, 2920 (CH) and 1594 (C=C).
1H NMR: 2.79 (s, 3H), 2.93-2.97 (dd, 2H), 3.75 (t, 1H), 7.40-7.89 (m, 3H) and 7.89-8.12 (m, 2H).
IR: 2916, 2846 (CH), 1660 (CO).
1H NMR: 2.84 (s, 3H), 2.64-3.70 (dd, 2H), 5.16-5.26 (s, br., 1H), 5.92 (s, br., 1H), 6.52 (s, br., 1H), 7.43-7.48 (m, 3H) and
8.03-8.05 (m, 2H).
IR: 3330, 3180 (NH2), 2916, 2846 (CH), 1690 (CO).
20
1H NMR: 2.86 (s, 3H), 5.13-5.14 (d, 1H), 5.71-5.75 (d, 1H), 6.92-7.27 (m, 6H), 7.43-7.48 (d, 2H) and 8.01-8.05 (d, 2H).
22a
22b
IR: 2916, 2846 (CH), 1712, 1635 (CO’s), 1635 (C=N)
1H NMR: 2.37 (s, 3H), 2.87 (s, 3H), 5.10-5.15 (d, 1H), 5.71-5.76 (d, 1H), 7.17-7.28 (m, 5H), 7.45-7.48 (d, 2H) and 8.01-
8.05 (d, 2H).
IR: 2916, 2850 (CH), 1716, 1635 (CO’s), 1635 (C=N)
1H NMR: 2.86 (s, 3H), 3.80 (s, 3H), 5.13-5.14 (d, 1H), 5.71-5.75 (d, 1H), 6.92-7.27 (m, 5H), 7.43-7.48 (d, 2H) and 8.01-
8.05 (d, 2H).
22c
IR: 2916, 2846 (CH), 1712, 1635 (CO’s), 1635 (C=N)
Elemental analyses were carried out at the Microanalytical
Center of the Cairo University. Hydroximoyl chlorides 11a-d
were prepared using previously described methods [7,9-12].
and 2-(4-Methyl-2-phenyl-1,3-thiazol-5-yl)-3-nitrosoimi-
dazo[1,2-c]pyrimidine (7).
General Procedure.
2-Chloro-2-(hydroximino)-1-(4-methyl-2-phenyl)thiazol-5-
yl)ethanone (2).
A mixture of 2 and the appropriate of 2-aminopyridine or 2-
amino-3-methylpyridine or 2-amino-pyrimidine (5 mmol for
each) in ethanol (20 ml) was stirred for 2 hours. The resulting
solid was collected, washed with water and recrystallized from
dioxan to give 3a,b and 7, respectively (Tables 2 and 3).
Hydrochloric acid (12 M, 100 ml) was added while stirring to a
mixture of 1 (11.2 g, 40 mmol), sodium nitrite (3.5 g, 50 mmol)
in dioxn (50 ml) and water (50 ml) at 25 °C. Stirring was contin-
ued for 3 hours to produce a pale yellow solid, which was sepa-
rated by filtration and recrystallized from ethanol to give 2
(Tables 2 and 3).
Synthesis of 2-(4-Methyl-2-phenyl-1,3-thiazol-5-yl)imidazo-
[1,2-a]pyridine (6).
Equimolar amounts of 2-bromo-1-(4-methyl-2-phenyl-1,3-
thiazol-5-yl)ethanone and 2-aminopyridine (5 mmol for each)
in ethanol (20 ml) were heated under reflux for 2 hours. The
Synthesis of 2-(4-Methyl-2-phenyl-1,3-thiazol-5-yl)-3-
nitrosoimidazo[1,2-a]pyridine (3a), 6-Methyl-2-(4-methyl-2-
phenyl-1,3-thiazol-5-yl)-3-nitrosoimidazo[1,2-a]pyridine (3b)

254
A. O. Abdelhamid, A. H. Elghandour, S. A. Ahmed and Y. H. Zaki
Vol. 43
resulting solid was collected, washed with water and recrystal-
lized from dioxan to give 6 (Tables 2 and 3).
each) in toluene (30 ml) was heated under reflux for 18 hours.
The solvent was evaporated under vacuum and the residual oil
was triturated with petroleum ether (40-60 °C). A solid was col-
lected and recrystallized from ethanol to give 19, 20 and 22a-c,
respectively (Tables 2 and 3).
Synthesis of 1,4-Dihydro-2-(4-methyl-2-phenylthiazol-5-yl)-3-
nitrosoquinoxaline (8a), 3-(4-Methyl-2-phenylthiazol-5-yl)-2-
nitroso-4H-benzo[b]thiazine (8b), 3-(4-Methyl-2-phenylthiazol-
5-yl)-2-nitroso-4H-benzo[b]oxazine (8c).
Alternative Method for Synthesis of 3-[(4-Methyl-2-phenyl-
1,3-thiazol-5-yl)carbonyl]-4,5-dihydroisoxazole-5-carbox-
amide (20).
General Procedure.
Equimolar amounts of 2 and the appropriate of o-phenylenedi-
amine, o-aminothiophenol or 2-aminophenol (5 mmol for each)
in ethanol (20 ml) were stirred for 2 hours (or boiled under reflux
in case of 2-aminophenol). The resulting solid was collected,
washed with water and recrystallized from dioxan to give 8a, 8b
and 8c, respectively (Tables 2 and 3).
Compound 19 (0.5 g) and sulphuric acid (5 ml) was stirred at
room temperature for 1 hour, and then poured onto crushed ice
(20 g). The resulting solid was collected and recrystallized from
ethanol to give 20 (Tables 2 and 3).
REFERENCES
Synthesis of 2-(4-Methyl-2-phenyl-1,3-thiazol-5-yl)-3-nitroso-
quinoxaline (10).
[1] P. N. Preston, " The Chemistry of Heterocyclic
Compounds" Wiley & Sons, New York, 1980, Vol. 40/11, 53 1.
[2] N. Aral, M. Iwakoshi, K. Tanabe and K. Narasaka, Bull.
Soc. Japan., 72, 2277, (1999).
[3] Y. Chen and C. Nan Li, Journal of Chin. Chem. Soc., 40,
203, (1993).
A solution of 8a (0.5 g) in acetic acid (15 ml) and hydrogen
peroxide (30%, 5 ml) was stirred at room temperature for 24
hours. The reaction was poured onto water (50 ml), the resulting
solid was collected and recrystallized from dioxan to give 10
(Tables 2 and 3).
[4] T. Sasaki, T. Yoshioka and Y. Suzuki, Bull. Soc. Japan.,
44, 185, (1971).
Synthesis of 4-[(4-Methyl-2-phenylthiazol-5-carbonyl)-isoxazol-
3-yl]-substituted Methanone (15a-e).
[5] H. Dahn, B. Favre and J-P. Leresche, Helv. Chim. Acta,
56, 34, (1973).
General Method.
[6] G. Bal, P. V. Veken, D. Antonov, A. M. Lambeir, P.
Grellier, S. L. Croft, K. Augustyns and A. Haemers, Bioorganic &
Med. Chem. Letters, 13, 2875, (2003).
[7] C. Parkanyi, A. O. Abdelhamid, J. C. S. Chang and A. S.
Shawall, J. Heterocycl. Chem. 21, 1029 (1984).
[8] S. S. Gabrial and A. O. Abdelhamid, Arch Pharm.
(Weinheim), 320, 1281 (1987).
Triethylamine (0.5 g (0.75 ml), 5 mmol) was added dropwise
to an equimolar amount of each 11 and the appropriate hydroxi-
moyl chlorides 12a-e (5 mmol) in dry toluene (20 ml) while stir-
ring at 0-5 °C. The reaction mixture was stirred for 6 hours. The
reaction mixture was filtered, the filtrate was evaporated and the
resulting oil was triturated with petroleum ether (40-60 °C). The
solid, so formed, was collected and recrystallized to give 15a-e,
respectively (Tables 2 and 3).
[9] A. O. Abdelhamid, F. A. Khalifa and S. S. Gabrial,
Phosphorus and Sulfur, 40, 41 (1988).
[10] A. O. Abdelhamid, A. M. Negem, T. M. S. Abdeen, Arch
Pharm. (Weinheim), 321, 913 (1988).
Synthesis of 4-(4-Methyl-2-phenyl-1,3-thiazol-5-yl)-7-substi-
tutedisoxazolo[3,4-d]pyridazine (17a-e).
[11] A. O. Abdelhamid, S. E. Abdou and S. A. Mahgoub,
General Method.
Arch. Res., 15, 317 (1992).
[12] A. 0. Abdelhamid and A. A. Al-Hamidi, J. Chin. Chem.
Soc., 42, 83 (1995).
[13] H. F. Zohdi, T. A. Osman and A. O. Abdelhamid, J.
Chin. Chem. Soc., 44, 617 (1997).
[14] A. M. Farag, K. M. Dawood and A. O. Abdelhamid,
Tetrahedron, 53, 17461 (1997).
Equimolar amounts of each of the appropriate isoxazoles 15a-
e (5 mmol) and hydrazine hydrate (1 ml, 99%) in ethanol (20 ml)
was boiled under reflux for 2 hours. The resulting solid was col-
lected and recrystallized from dioxane to give isoxazolo [3,4-d]-
pyridazines 17a-e, respectively (Tables 2 and 3).
Synthesis of 3-[(4-Methyl-2-phenyl-1,3-thiazol-5-yl)car-
bonyl]-4,5-dihydroisoxazole-5-carbonitrile (19), 3-[(4-Methyl-2-
phenyl-1,3-thiazol-5-yl)carbonyl]-4,5-dihydroisoxazole-5-car-
boxamide (20) and 3-[(4-Methyl-2-phenyl-1,3-thiazol-5-yl)car-
bonyl]-5-substituted3aH-pyrrolo[3,4-d]isoxazole-4,6(5H,6aH)-
dione (22a-c).
[15] A. O. Abdelhamid, N. M. Abed and F. M. Al-Fayez,
Phosphorus, Sulfur and Silicon., 150, 35-52 (2000).
[16] Y. H. Zaki, S. A. Ahmed, A. M. Hussein and A. O.
Abdelhamid. Phosphorus, Sulfur and Silicon, in press (2005).
[17] L.J. Bellamy, "The Infrared Spectra of Complex
rd.
Molecules" 3 Ed., John Wiley, N.Y., London, 1975, p 150.
[18] N.E. Searle, U.S. Pat. 2 444 536 (1948); Chem. Abstr,
42, 7340 (1948).
General Method.
An equimolar amount of the appropriate 2, acrylonitrile or
acryloamide or the appropriate N-arylmalemides 22a-c (5 mmol
[19] W. E. Solomons, N. J. Doorenbos, J. Pharm. Sci, 63, 19
(1974).