Synthesis of some new thiazole, thiophene, and 2,3-dihydro-1,3,4- thiadiazole and pyrimidino[1,2-b]indazole derivatives

Article abstract of DOI:10.1080/104265090921083

Hydrazonoyl halides 4a-g reacted with methyl carbodithioate 3 thioanilide 10 to give 1,3,4-thiadiazoles 5a-g and 13a-g, respectively. Thioanilide 10 reacted with ω-bromoacetophenones 14a-e to give the acyclic product 15a-e, which was converted to the thio

Full text of DOI:10.1080/104265090921083

This article was downloaded by: [Selcuk Universitesi]
On: 19 January 2015, At: 01:52
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
Synthesis of Some New
Thiazole, Thiophene, and 2,3-
Dihydro-1,3,4-thiadiazole and
Pyrimidino[1,2-b]indazole
Derivatives
Nora M. Rateb a
a Cairo University, Chemistry Department , Giza,
Egypt
Published online: 22 Aug 2006.
To cite this article: Nora M. Rateb (2005) Synthesis of Some New Thiazole,
Thiophene, and 2,3-Dihydro-1,3,4-thiadiazole and Pyrimidino[1,2-b]indazole
Derivatives, Phosphorus, Sulfur, and Silicon and the Related Elements, 180:10,
2361-2372, DOI: 10.1080/104265090921083
To link to this article: http://dx.doi.org/10.1080/104265090921083
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, 180:2361–2372, 2005
Copyright © Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/104265090921083
Synthesis of Some New Thiazole, Thiophene,
and 2,3-Dihydro-1,3,4-thiadiazole
and Pyrimidino[1,2-b]indazole Derivatives
Nora M. Rateb
Chemistry Department, Cairo University, Giza, Egypt
Hydrazonoyl halides 4a–g reacted with methyl carbodithioate 3 thioanilide 10 to
give 1,3,4-thiadiazoles 5a–g and 13a–g, respectively. Thioanilide 10 reacted with ω-
bromoacetophenones 14a–e to give the acyclic product 15a–e, which was converted
to the thiophenes 16a–e and to the thiazoles 17a–e, respectively. Structures of the
newly synthesized compounds were elucidated on the basis of elemental analysis,
spectral data, and alternative synthesis route whenever possible.
Keywords Dimidone; hydrazonoyl halides; thiophene; thiazoles; thiadiazoles
INTRODUCTION
Thiazoles1,2 and thiadiazoles have been found to exhibit diverse biologi-
cal activities. They act as anticarcinogenic,3 fungicidal,4,5 herbicidal,6,7
lubricant,8 and antitumor9 agents. In continuation of our previous
work,10−13 on the synthesis of different thiazoles, thiophenes, and 1,3,4-
thiadiazoles with potential biological activities, we report the synthesis
of some new thiazole, thiophene, 1,3,4-thiadiazole, and pyrimidino[1,2-
b]indazole derivatives via the reaction of dimidone with different sulfur-
containing compounds.
RESULTS AND DISCUSSION
The reaction of equimolar amounts of 3-{aza[(methylthiothioxom
ethyl) amino]methylene}-5,5-dimethylcyclohexane-1-one (3) (which
was prepared from the reaction of dimidone and methylhy-
drazinecarbodithioate in isopropyl alcohol) and C-ethoxycarbonyl-
N-phenylhydrazonoyl chloride (4a) in ethanolic triethylamine solution
Received September 7, 2004; accepted October 22, 2004.
Address correspondence to Nora M. Rateb, Cairo University, Chemistry Department,
Faculty of Science, Giza, Egypt. E-mail: noraratb@hotmail.com
2361

2362
N. M. Rateb
afforded product 5a. The structure 5a was assigned as ethyl 2-
[1,2-diaza-2-(5,5-dimethyl-3-oxocyclohexylidene)ethylidene]-3-phenyl-
1,3,4-thiadiazoline-5-carboxylate based on elemental analysis, spectral
data, and independent synthesis. 1H NMR spectrum of 5a showed
signals at δ = 1.03 (s, 6H, 2 CH3), 1.37 (t, 3H, CH2CH3), 2.21 (s, 2H,
CH2), 2.34 (s, 2H, CH2), 4.39 (q, 2H, CH2CH3), 4.22 (s, 2H, CH2), and
7.25–7.80 (m, 5H, ArH’s). Its IR spectrum (cm−1) revealed absorption
bands at 1723 and 1666 (CO’s). Also, compound 5a was obtained
by the reaction of 2-hydrazino-2,3-dihydro-1,3,4-thiadiazole14 6 with
dimidone (Scheme 1).
The formation of 5a can be explained via elimination of methyl mer-
captan from the corresponding cyclo adduct 9a, which is assumed to
be formed from 1,3 dipolar cycloaddition of 4a to C S in 3. Alterna-
tively, formation of 5a can also be explained by the 1,3 addition of 3 to
the nitrilium imide 7a (which is prepared in situ by treatment of hydra-
zonoyl bromide 4a with triethylamine) to give 8a which readily cyclized
to yield 9a, which, in turn, affords 5a by the loss of methyl mercaptan
molecule. Similarly, compound 3 reacted with the appropriate hydra-
zonoyl halides 4b–g to afford 2,3-dihydro-1,3,4-thiadiazole derivatives
5b–g, respectively.
2-(Mercapto- phenylamino-methylene)-5,5- dimethyl- cyclohexane-
1,3 - dione15 (10) with C-ethoxycarbonyl-N-phenylhydrazonoyl chloride
(4a) in N,N-dimethylformamide contains potassium hydroxide to give
one isolable product, according to TLC, which seemed to be either
12 or 13. The structure of the product was elucidated on the basis
of elemental and spectral data. Thus, IR spectrum (cm−1) revealed
bands at 1710, 1616, and 1620 (3 CO’s). Its 1H NMR spectrum showed
signals at δ = 1.10 (s, 6H, 2 CH3), 1.43 (t, 3H, CH3CH2), 2.33 (s, 2H,
CH2), 2.37 (s, 2H, CH2), 4.48 (q, 2H, CH3CH2), and 7.13–7.32 (m, 5H,
ArH’s). More evidence of the structure 13 can be obtained from the
reaction of 10 with C-ethoxycarbonyl-N-p-tolylhydrazonoyl chloride
(4h) under the same condition which gave a product having an 1H
NMR spectrum which showed signals at δ = 1.10 (s, 6H, 2 CH3), 1.43
(t, 3H, CH3CH2), 2.33 (s, 2H, CH2), 2.37 (s, 2H, CH2), 2.43 (s, 3H,
4-CH3C6H4), 4.48 (q, 2H, CH3CH2), and 7.13–7.32 (m, 5H, ArHs).
Based on the spectral data and the elemental analysis, structure 12
was ruled out and the product was assigned as ethyl 2-(4,4-dimethyl-
2,6-dioxocyclohexylidene)-3-phenyl-1,3,4-thiadiazoline-5-carboxylate
(13a). The formation of product 13a can be explained via the reaction
of 10 with hydrazonoyl chloride 4a to form the intermediate 11, which
lost an aniline molecule11 to give the final product 13a (Scheme 2).
By analogy, thioamide 10 reacted with the appropriate hydrazonoyl
halides 4b–g to afford the 2,3-dihydro-1,3,4-thiadiazoles derivatives
13b–g, respectively. For example, the 1H NMR spectrum of 13e showed

Synthesis of Thiazole Derivatives
2363
SCHEME 1

2364
N. M. Rateb
SCHEME 2

Synthesis of Thiazole Derivatives
2365
signals at δ = 1.06 (s, 6H, 2 CH3), 2.49 (s, 2H, CH2), 2.65 (s, 2H, CH2),
and 7.15–7.50 (m, 10H, ArHs). Its 13C NMR spectrum showed signals
at δ = 28.7, 31.1, 51.4, 105.7, 122.9, 128.9, 129.1, 130.8, 134.4, 134.8,
143.2, 183.3, and 191.9.
Treatment of
1
with phenyl isothiocyanate in N,N-
dimethylformamide containing potassium hydroxide was followed
by the appropriate ω-bromoacetophenones 14a–e to afford the acyclic
products 15a–e,0 respectively. Structure 15 was established on the
basis of elemental analysis, spectral data, and chemical transforma-
tion. For example, 1H NMR spectrum of compound 15d showed signals
at δ = 1.09 (s, 6H, 2 CH3), 2.43 (s, 2H, CH2), 2.80 (s, 2H, CH2), 4.23
(s, 2H, SCH2), 7.11–7.88 (m, 9H, ArH’s), and 11.24 (s, 1H, NH). Its
IR spectrum (cm−1) revealed absorption bands at 1650, 1620, 1618
(CO’s), and 3425 (NH). Thus, compound 15a–e can be converted to the
thiophenes 16a–e by boiling in ethanol containing catalytic amount
of piperidine. In contrast, the appropriate 15a–e, when treated with
conc. sulfuric acid at room temperature, was converted to the thiazoles
17a–e respectively. The structure of these products was established
on the basis of elemental analysis and spectral data (Scheme 3). For
example, 13C NMR spectrum of 16c showed signals at δ = 28.5, 34.3,
41.2, 52.0, 116.2, 118.3, 119.6, 125.0, 128.9, 129.9, 130.0, 138.1, 139.0,
139.3, 149.5, 162.4, 187.2, and 196.4. Its mass spectrum showed m/z
peaks at 409, 410, 412, 394, 270, 214, 142, 139, and 77.
Compound 10 reacted with iodomethane in N,N-dimethylformamide
containing
potassium
hydroxide
to
give
5,5-dimethyl–2-
(18),
[methylthio(phenylamino)methylene]-cyclohexane-1,3-dione
which reacted with hydrazine hydrate in ethanol under reflux to give
6,6-dimethyl-3-phenylamino-2,5,6,7-tetrahydro-1H-indazol-4-one (20)
(Scheme 4). Structure 20 was elucidated on the basis of elemental
1
analysis and spectral data. Thus, H NMR showed signals at δ = 1.03
(s, 6H, 2 CH3), 2.43 (s, 2H, CH2), 2.60 (s, 2H, CH2), 6.96–7.96 (m, 5H,
ArHs), 9.13 (s, 1H, NH) and 12.40 (s, 1H, NH). Its mass spectrum
showed m/z peaks 255, 212, 199, 170, 142, 115, 77, and 51 and the
product obtained is free from sulfur. It was also prepared from the
reaction of 10 with hydrazine hydrate in ethanol under reflux to give
an identical product in all respects. (m.p., mixed m.p., and spectra). The
reaction of 20 with ethylacetoacetate and with its trifluoro analogue in
acetic acid afforded 21a and 21b, respectively.
EXPERIMENTAL
All melting points were determined on an electrothermal apparatus and
are uncorrected. IR spectra were recorded (on KBr discs) on a Shimadzu

2366
N. M. Rateb
SCHEME 3
FT-IR 8201 PC spectrophotometer. 1H NMR spectra were recorded in
CDCL3 and (CD3)2SO solutions on a Varian Gemini 300 MHz spectrom-
eter and chemical shifts were expressed in δ using TMS as internal ref-
erence. 13C NMR spectra were recorded in CDCL3 solutions on a Varian
Gemini 75 MHz spectrometer and chemical shifts were expressed in δ
using TMS as internal reference. MS spectra were recorded on a GC-MS
HP 5889A. Elemental analysis was carried out at the Microanalytical
Center, Cairo University. Thiadiazole14 6, thioanilide15 10, hydrazonoyl
halides16−23 4a–g, and hydrazine carbodithioate24 2 were prepared as
reported.
Synthesis of 3-{aza[(methylthiothioxomethyl)
amino]methylene}-5,5-dimethylcyclohexane-1-one (3)
A
mixture of dimidone 1 (0.05 mole) and methyl hydrazine
carbodithioate24 2 (0.05 mole) was stirred in isopropyl alcohol for 1 h.
The formed solid was collected by filtration and crystallized from acetic
acid to give 3 (Tables I–III).

Synthesis of Thiazole Derivatives
2367
SCHEME 4
Synthesis of 2,3-Dihydro-1,3,4-thiadiazole Derivatives 5a–g
A mixture of 3 (0.005 mole), the appropriate hydrazonoyl halides16−23
4a–g (0.005 mole), and triethylamine (0.005 mole) in ethanol
(20 mL) was stirred for 30 min. The resulting solid was collected
and crystallized from the proper solvent to give 5a–g (Tables I–
III).
Synthesis of 2,3-Dihydro-1,3,4-thiadiazole Derivatives 13a–h
A mixture of 1 (0.01 mole), phenyl isothiocyanate (0.01 mole), and
potassium hydroxide (0.01 mole) in N.N-dimethylformamide (20 mL)
was stirred for 3 h at room temperature. The appropriate hydrazonoyl

2368
N. M. Rateb
TABLE I Characterization Data of the Newly Synthesized
Compounds
% Analyses, calcd./found
Compound
no.
Mp.,◦C
solvent
Colour
yield %
Mol. formula
(Mol. Wt.)
C
H
N
S
3
210–13
ACOH
115–17
EtOH
180–83
EtOH
155–56
EtOH
140–43
EtOH
80–83
EtOH
185–86
EtOH
120–22
EtOH
138–40
EtOH
245–47
DMF
138–40
EtOH
199–200
EtOH
209–11
ACOH
147–50
ACOH
217–20
ACOH
138–40
EtOH
Yellow
89
Yellow
65
Yellow
67
Yellow
59
Orange
55
Red
59
Red
55
Brown
75
Yellow
75
Yellow
79
Yellow
73
Orange
80
Orange
75
Orange
79
Yellow
78
White
85
White
87
White
83
Yellow
85
Orange
78
Yellow
80
Yellow
75
C10H16N2OS2
(244.38)
49.15
49.00
59.05
59.20
63.72
63.50
67.67
67.80
60.65
60.40
66.01
66.30
69.21
69.00
59.41
59.60
61.27
61.40
65.85
65.60
70.19
70.30
63.14
63.30
68.30
68.10
71.35
71.50
61.44
61.20
70.20
70.40
70.73
70.90
64.55
64.20
58.48
58.40
63.00
63.20
73.57
73.30
74.01
73.90
6.60
6.50
5.74
5.90
5.35
5.10
5.68
5.80
5.66
5.40
5.30
5.50
5.16
4.90
4.75
4.80
5.41
5.30
5.05
4.90
5.35
5.10
5.30
5.00
4.98
5.00
4.88
5.00
4.42
4.20
5.89
6.00
6.18
6.30
5.18
4.90
4.49
4.50
5.06
5.20
5.64
5.40
5.95
6.00
11.46
11.30
14.50
14.70
16.15
15.90
14.35
14.50
15.72
15.50
13.39
13.50
11.96
11.70
13.20
13.40
7.52
7.30
10.02
9.90
7.44
7.20
8.18
8.00
6.93
6.70
6.16
6.00
6.82
6.60
3.56
3.70
3.44
3.60
3.27
3.10
2.96
2.90
6.39
6.50
3.73
3.50
26.24
26.10
8.30
8.50
7.40
7.20
8.21
8.00
9.00
8.90
7.66
7.80
6.84
6.60
15.11
15.30
8.61
8.60
7.64
7.40
8.52
8.30
9.36
9.20
7.93
7.80
7.05
6.90
15.62
15.40
8.15
8.30
7.87
7.90
7.49
7.50
6.79
6.70
7.31
7.50
8.54
8.30
8.23
8.20
5a
C
19H22N4O3S
(386.48)
5b
C23H23N5O2S
(433.54)
5c
C
22H22N4OS
(390.51)
5d
C
18H20N4O2S
(356.45)
5e
C23H22N4O2S
(418.52)
5f
C
27H24N4O2S
(468.58)
5g
C21H20N4O2S2
(424.55)
13a
13b
13c
13d
13e
13f
13g
15a
15b
15c
15d
15e
16a
16b
C
C
C
C
19H20N2O4S
(372.45)
23H21N3O3S
(419.51)
22H20N2O2S
(376.48)
18H18N2O3S
(342.42)
C23H20N2O3S
(404.49)
C
27H22N2O3S
(454.55)
C
21H18N2O3S2
(410.52)
C23H23NO3S
(393.51)
145–46
EtOH
C24H25NO3S
(407.54)
C23H22ClNO3S
(427.95)
160–62
ACOH
159–60
ACOH
190–92
ACOH
150–51
EtOH
C23H22BrNO3S
(472.40)
C
23H22N2O5S
(438.51)
C
23H21NO2S
(375.49)
180–82
EtOH
C24H23NO2S
3.60
3.50
(389.52)

Synthesis of Thiazole Derivatives
2369
TABLE I Characterization Data of the Newly Synthesized
Compounds (Continued)
% Analyses, calcd./found
Compound
no.
Mp.,◦C
solvent
Colour
yield %
Mol. formula
(Mol. Wt.)
C
H
N
S
16c
16d15
16e
17a
17b
17c
17d
17e
18
159–60
EtOH
165–67
EtOH
188–90
EtOH
250–53
EtOH
>340
EtOH
296–300
EtOH
282–85
EtOH
269–70
EtOH
135–37
EtOH
235–36
EtOH
278–80
ACOH
268–70
ACOH
Yellow
79
Yellow
75
Yellow
84
White
75
White
73
Yellow
69
Yellow
75
Yellow
79
White
55
Yellow
79
Yellow
65
Yellow
63
C23H20ClNO2S
(409.94)
C23H20BrNO2S
(454.39)
C23H20N2O4S
(420.49)
67.39
67.20
60.80
60.60
65.70
65.50
73.57
73.40
74.01
73.90
67.39
67.30
60.80
60.70
65.70
65.60
66.41
66.20
70.56
70.40
71.01
71.00
60.80
60.60
4.92
4.70
4.44
4.20
4.79
4.60
5.64
5.50
5.95
6.00
4.92
4.90
4.44
4.30
4.79
4.70
6.62
6.40
6.71
6.50
5.96
6.00
4.30
4.10
3.42
3.20
3.08
2.90
6.66
6.40
3.73
3.60
3.66
3.50
3.42
3.30
3.08
3.10
6.66
6.50
4.84
4.60
16.46
16.20
13.07
13.00
11.19
11.00
7.81
7.60
7.06
7.00
7.63
7.40
8.54
8.30
8.23
8.20
7.82
7.60
7.06
7.00
7.63
7.50
11.08
10.90
C
23H21NO2S
(375.49)
C24H23NO2S
(389.52)
C
23H20ClNO2S
(409.94)
C
23H20BrNO2S
(454.39)
C23H20N2O4S
(420.49)
C
16H19NO2S
(289.40)
20
C15H17N3O
(255.32)
21a
21b
C
19H19N3O2
(321.38)
C19H16F3N3O2
(375.35)
halides 4a–h (0.01 mole) were added and stirring was continued for 2
h. The reaction mixture was diluted with water and the solid that was
precipitated was collected and crystallized from the proper solvent to
give 13a–g (Tables I–III).
Synthesis of 5,5-Dimethyl-2-[(2-oxo-2-arylethylthio)(phenyl-
amino)-methylene] cyclohexane-1,3-dione 15a–e
A mixture of 1 (0.01 mole), phenyl isothiocyanate (0.01 mole),
and potassium hydroxide (0.01 mole) in N,N-dimethylformamide (20
mL) was stirred for 3 h at room temperature. The appropriate ω´-
bromoacetophenones 14a–e (0.01 mole) was added and stirring was
continued for 2 h. The formed solid was collected and crystallized from
the proper solvent to give 15a–e (Tables I–III).

2370
N. M. Rateb
TABLE II 1H NMR Spectrum of Some Newly Synthesized Compounds
Compound
no.
1H NMR (δ ppm)
3
1.03 (s, 6H, 2 CH3), 2.07 (s, 2H, CH2), 2.21 (s, 2H, CH2), 2.31 (s, 3H,
SCH3), 4.28 (s, 2H, CH2), and 11.56 (s, 1H, NH).
5e
1.06 (s, 6H, 2 CH3), 2.44 (s, 2H, CH2), 2.68 (s, 2H, CH2), 4.22 (s, 2H,
CH2) and 7.39–8.23 (m, 10H, ArHs).
13b
13d
15a
15b
1.03 (s, 6H, 2 CH3), 2.30 (s, 2H, CH2), 2.50 (s, 2H, CH2), 7.20–7.80 (m,
10H, ArHs) and 10.81 (s, 1H, NH).
1.01 (s, 6H, 2 CH3), 2.33 (s, 3H, CH3CO), 2.50 (s, 2H, CH2), 2.66 (s, 2H,
CH2) and 7.15–7.50 (m, 5H, ArHs).
1.21 (s, 6H, 2 CH3), 2.35 (s, 2H, CH2), 2.96 (s, 2H, CH2), 4.23 (s, 2H,
SCH2), 7.07–8.05 (m, 10H, ArHs), and 11.28 (s, 1H, NH).
1.25 (s, 6H, 2 CH3), 2.33 (s, 2H, CH2), 2.52 (s, 2H, CH2), 2.32 (s, 3H,
4-CH3C6H4), 4.26 (s, 2H, SCH2), 7.07–7.91 (m, 9H, ArHs) and 11.26
(s, 1H, NH).
15c
15d
16b
21a
21b
1.04 (s, 6H, 2 CH3), 2.08 (s, 2H, CH2), 2.20 (s, 2H, CH2), 4.75 (s, 2H,
SCH2), 7.06–8.03 (m, 9H, ArHs), and 11.23 (s, 1H, NH).
1.09 (s, 6H, 2 CH3), 2.43 (s, 2H, CH2), 2.80 (s, 2H, CH2), 4.30 (s, 2H,
SCH2), 7.11–7.88 (m, 9H, ArHs), and 11.24 (s, 1H, NH).
1.00 (s, 6H, 2 CH3), 2.32 (s, 2H, CH2), 2.31 (s, 3H, 4-CH3C6H4), 2.70 (s,
2H,CH2), 7.01–7.69 (m, 9H, ArHs), and 11.32 (s, 1H, NH).
1.06 (s, 6H, 2 CH3), 2.29 (s, 2H, CH2), 2.68 (s, 2H, CH2), 2.92 (s, 3H,
CH3), and 7.07–8.05 (m, 6H, ArH’s and CH).
1.06 (s, 6H, 2 CH3), 2.29 (s, 2H, CH2), 2.68 (s, 2H, CH2), and 7.07–8.05
(m, 6H, ArH’s and CH).
Synthesis of 6,6-Dimethyl-3-(phenylamino)-1-(arylcarbonyl)-
5,6,7-trihydrobenzo[2,1-c]thiophen-4-one 16a–e
Compounds 15a–e (0.005 mole) were refluxed in ethanol (20 mL) that
contained a catalytic amount of piperidine for 1 h. The resulting solid
was collected and cyrstallized from the proper solvent to give 16a–e
(Tables I–III).
Synthesis of 2-(4-(Substituted)-3-Phenyl-(1,3-thiazolin-2-ylide-
ne))-5,5-dimethyl-cyclohexane-1,3-dione 17a–e
A mixture of 15a–e (0.005 mole) with conc. sulfuric acid (10 mL) was
stirred for 1 h at room temperature and then poured on to ice. The
formed solid was collected and crystallized from the proper solvent to
give 17a–e (Tables I–III).
Synthesis of 5,5-Dimethyl-2-[methylthio(phenylamino)
methylene]-cyclohexane-1,3-dione (18)
A mixture of 1 (0.01 mole), phenyl isothiocyanate (0.01 mole), and potas-
sium hydroxide (0.01 mole) in N,N-dimethylformamide (20 mL) was

Synthesis of Thiazole Derivatives
2371
TABLE III Mass Spectra of Some Newly Synthesized
Compounds
Compound
no.
M+ m/z
244, 196, 171, 146, 110, 83, 55.
3
5b
5d
5e
5f
433, 404, 377, 323, 296, 244, 188, 110, 91, 77.
356, 357, 341, 328, 313, 300, 255, 205, 187, 135, 110, 77.
418, 403, 375, 313, 255, 198, 161, 105, 77.
468, 385, 331, 312, 242, 155, 127, 77.
424, 381, 288, 276, 196, 171, 111, 83.
454, 407, 225, 155, 127, 77.
410, 326, 313, 245, 217, 143, 111, 77.
407, 374, 313, 274, 226, 165, 119, 91.
375, 376, 360, 214, 149, 105, 77.
5g
13f
13g
15b
16a
16e
17b
17c
17d
17e
420, 405, 150, 104, 77.
389, 375, 362, 329, 273, 238, 214, 152, 105, 84.
409, 410, 411, 412, 353, 312, 285, 247, 214, 168, 136, 77, 55.
453, 455, 358, 356, 275, 247, 180, 103, 77, 55.
420, 364, 323, 321, 147, 89, 55.
stirred for 3 h at room temperature. Iodomethane (0.01 mole) was added
and stirring was continued for 2 h. The formed solid was collected and
crystallized from ethanol to give 18 (Tables I and II).
Synthesis of 6,6-Dimethyl-3-(phenylamino)-2,5,6,7-tetrahydro-
1H-indazol-4-one (20)
A mixture of 18 (or 10) and hydrazine hydrate (0.01 mole) was refluxed
in ethanol (20 mL) for 2 h. The formed solid was collected and crystal-
lized from ethanol to give 20 (Tables I and II).
Synthesis of 2-Substituted-7,7-dimethyl-1,6,7,8,4a-
pentahydropyrimidino[1,2-b] 1H-indazole-4, 9-dione 21a,b
A mixture of 20 and ethylacetoacetate and trifluoromethyl ethylace-
toacetate was refluxed in acetic acid for 3 h. The formed solid was col-
lected and crystallized from acetic acid to give 21a and 21b, respectively
REFERENCES
[1] P. A. Lowe, in Heterocyclic Chemistry, vol. 1, p. 119, H. Suschitzky and O. Meth-cohn
(Ed.), London: Chemical Society. (1980).

2372
N. M. Rateb
[2] J. V. Metzger, Comprehensive Heterocyclic Chemistry, vol. 6, Thiazoles and their
benzoderivatives, p. 328, A. R. Katritzky and C. W. Rees (Ed.), Perganon Press,
New York (1984).
[3] Kowa Co. Ltd., Jpn Kokai 80 28 946 (1980); Chem. Abstr., 93, 114536 (1980).
[4] Inst. Phys. Chem. Res., Jpn. Kokai 77 25028 (1977); Chem. Abstr., 87, 147054 (1977).
[5] S. P. Singh and S. Segal, Indian J. Chem., 27B, 941 (1988).
[6] Hokko Chem. Ind. Co. Ltd., Br. Pat. 1 266 542 (1972); Chem. Abstr., 77, 5474 (1972).
[7] P. Goursot and E. F. Jr. Westrum, J. Chem. Eng. Data, 14, 1 (1969).
[8] Lubrizol Crop., U. S. Pat. 4246 126 (1981); Chem. Abstr., 94, 142505 (1981).
[9] F. Kuzer, Org. Compd. Sulfur, Selenium, Tellurium, 4, 431 (1977).
[10] A. O. Abdelhamid, N. M. Rateb, and K. M. Dawood, Phosphorus , Sulfur, and Silicon,
167, 251 (2000).
[11] A. O. Abdelhamid, H. F. Zohdi, and N. M. Rateb, J. Chem. Res. (S), 184, (M)920
(1999).
[12] N. M. Rateb, N. A. Abdel-Riheem, A. A. Al-Atoom, and A. O. Abdelhamid, Phospho-
rus, Sulfur, and Silicon, 178, 1101 (2003).
[13] N. A. Abdel-Riheem, N. M. Rateb, A. A. Al-Atoom, and A. O. Abdelhamid, Heteroatom
Chemistry, 14, 421 (2003).
[14] H. F. Zohdi, N. M. Rateb, M. M. M. Sallam, and A. O. Abdelhamid, J. Chem. Res.
(S), 742, (M)3329 (1998).
[15] S. Garges, H. Kristen, K. Pescke, and I. Forkas, J. Parkt. Chem., 325, 143 (1983).
[16] A. S. Shawali and A. O. Abdelhamid, Bull. Che. Soc. Jpn., 49, 321 (1976).
[17] G. Fravel, Bull. Soc. Chim. Fr., 31, 150 (1904).
[18] N. F. Eweiss and A. Osman, Tetrahedron Lett., 1169 (1979).
[19] P. Wolkoff, Can. Chem., 53, 1333 (1975).
[20] A. Shawali and A. Osman, Tetrahedron, 27, 2517 (1971).
[21] A. O. Abdelhamid and F. H. H. El-Shaity, Phorphorus, Sulfur, and Silicon, 39, 45
(1988).
[22] A. O. Abdelhamid, F. A. Khalifa, F. A. Attaby, and S. S. Ghabrial, Arch. Pharm. Res.,
15, 14 (1992).
[23] H. M. Hassaneen, A. S. Shawali, N. M. Elwan, and N. M. Abounada, Sulfur Lett.,
14, 41 (1972).
[24] D. L. Klayman, J. F. Bartosevich, T. S. Gruffin, C. J. Manson, and J. P. Scovill, J.
Med. Chem., 22, 825 (1979).