Utility of 2-[4-(3-oxobenzo[f]-2H-chromen-2-yl)-1,3-thiazol-2-yl] ethanenitrile in heterocyclic synthesis

Article abstract of DOI:10.1002/jhet.5570450625

(Chemical Equation Presented) Pyrazolo[4,3-d]pyrimidines, pyrazolo[4,3-d]triazolino[4,3-a]pyrimidines, 3-(2-thiazolyl)thiophenes, thiazolo[3,2-a]pyridine and pyrazolo[1,5-a]pyrimidines were synthesized from 2-[4-(3-oxobenzo[f]-2H-chromen-2-yl)-1,3-thiazol-2-yl]ethanenitrile. The newly synthesized compounds were elucidated by elemental analysis, spectral data, chemical transformation and alternative synthesis route whenever possible.

Full text of DOI:10.1002/jhet.5570450625

Nov-Dec 2008
1719
Utility of 2-[4-(3-Oxobenzo[f]-2H-chromen-2-yl)-1,3-thiazol-2-
yl]ethanenitrile in Heterocyclic Synthesis
Abdou O. Abdelhamid and Hassan M. Abdelaziza
Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt
aDepartment of Chemistry, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt
Abdelhamid45@gmail.com
Received March 22, 2007
R
R
N
N
S
S
H
N
Ph
A
S
S
N
O
CN
N
N
R
N
N
HN
N
N
N
Ar
O
O
Ar
R
R''
S
R
N
N
N
Ph
H2N
NC
S
PhHN
N
N
CN
CN
NH2
Ar
Pyrazolo[4,3-d]pyrimidines, pyrazolo[4,3-d]triazolino[4,3-a]pyrimidines, 3-(2-thiazolyl)thiophenes,
thiazolo[3,2-a]pyridine and pyrazolo[1,5-a]pyrimidines were synthesized from 2-[4-(3-oxobenzo[f]-2H-
chromen-2-yl)-1,3-thiazol-2-yl]ethanenitrile. The newly synthesized compounds were elucidated by
elemental analysis, spectral data, chemical transformation and alternative synthesis route whenever
possible.
J. Heterocyclic Chem., 45, 1719 (2008).
INTRODUCTION
heating 2-aminothioxomethyl-3-aza-3-(phenylamino)-
prop-2-enenitriles [9] (5a) with 1 in boiling ethanol.
Compounds 4a,b were reacted with ethyl chloroacetate
in boiling N,N-dimethylformamide solution containing
potassium carbonate and triethylamine to afford the
ethyl 4-amino-3-[4-oxobenzo[f]chromen-2-yl]-1,3-
Coumarin derivatives constitute an important class of
heterocyclic compounds with anticoagulant [1,2],
anticoagulant rodenticide [3], insecticide [4] and
antibacterial [5,6] pharmacolgical properties. On the other
hand, 1,3,4-thiadiazole derivatives have become very
useful compounds in medicine, agriculture and in many
other fields of technology [7]. We report here the
synthesis of some new pyrazolo[4,3-d]pyrimidines,
pyrazolo[4,3-d]triazolino[4,3-a]pyrimidines, 3-(2-thiazol-
yl)thiophenes, thiazolo[3,2-a]pyridine and pyrazolo[1,5-
a]pyrimidines.
thiazol-2-yl-1-arylpyrazole-5-carboxylates
6a,b.
Treatment of 6a,b with ammonium thiocyanate in
acetic acid under reflux afforded 2-[2-oxo-1-aryl-5-
thioxo-4,6-dihydropyrazolo[4,3-d]pyrimidin-3-yl-1,3-
thiazol-4-yl]-benzo[f]chromen-3-one 7a,b. Compound
7 was elucidated on the basis of elemental analysis,
spectral data and chemical transformation. Thus,
treatment of 7a,b with each of ethyl chloroacetate and
iodomethane afforded 1-aryl-3-[4-(3-oxobenzo[f]-2H-
chromen-2yl)-1,3-thiazol-2-yl]-7a-hydro-6H-pyrazolo-
[4,3-d]-1,3-thiazolidino[3,2-a]pyrimidine-4,8-dione 8a,b
RESULTS AND DISCUSSION
3-(2-Bromoacetyl)benzo[f]chromen-2-one [8] (1)
was heated with cyanothioacetamide (2) in ethanol
under reflux to give 2-[4-(3-oxobenzo[f]-2H-chromen-
2-yl)-1,3-thiazol-2-yl]ethanenitrile (3). Compound 3
was reacted with arendiazonium chloride in ethanolic
sodium acetate solution at 0°C to afford 3-azo-2-[4-(3-
oxobenzo[f]-2H-chromen-2-yl)-1,3-thiazol-2-yl]-3-(aryl-
amino)prop-2-ene-nitrile 4a,b (Scheme 1). Compound
4 was elucidated by elemental analysis, spectral data,
and
1-aryl-2-[5-methylthio-7-oxo-6-hyd-ropyrazolo-
[4,5-d]pyrimidin-3-yl]-1,3-thiazol-4-yl)benzo[f]chromen-
3-one 9a,b (Scheme 2)
Treatment of 7a with the appropriate hydrazonyl
chlorides 10a,b in boiling chloroform containing triethyl-
amine gave ethyl 8-oxo-3-[4-(3-oxo-benzo[f]-2H-
chromen-2-yl)(1,3-thiazol-2-yl)]-1,5-diphenyl-7a-hydro-
pyrazolo[4,3-d]triazolino[4,3-a]pyrimidine-7-carboxylate
11a and 2-[2-(7-acetyl-8-oxo-1,5-diphenyl-7a-hydro-
alternative
synthesis
route
and
chemical
transformation. Compound 4a was also obtained by

1720
A. O. Abdelhamid and H. M. Abdelaziz
Vol 45
Scheme 1
COCH2Br
O
R
R
-
+
NH2
ArN2 Cl
1
NC
+
O
N
S
R =
N
S
+
S
zzz2
NC
NNHAr
NC
3
1
S
4
NC
NH2
ClCH2COOC2H5
N
NH
Ar
R
a, Ar = C6H5
b, Ar = 4-CH3C6H4
R
N
5
N
S
S
N
H
N
S
NH4SCN
N
N
H2N
HN
Ar
N
O
H5C2O2C
Ar
7
6
Scheme 2
R
N
S
a, Ar = C6H5
b, Ar = 4-CH3C6H4
N
N
N
S
N
10a, R'' = OC2H5
b, R'' = CH3
Ar
O
O
8
ClCH2COOC2H5
R
R
R
N
S
N
S
N
S
R''COC(Cl):NNHPh
CH3I
H
N
N
O
CH3S
HN
S
10
N
N
Ph
N
N
O
N
N
N
N
HN
N
O
Ar
N
Ar
Ar
O
9
7
R"
11a, R'' = OC2H5, Ar = C6H5
b, R'' = OC2H5, Ar = 4-CH3C6H4
c, R'' = CH3, Ar = C6H5
d, R'' = CH3, Ar = 4-CH3C6H4
double bond to give spiro intermediate 14, which was
afforded 11 directly via intermediate 15 by loss hydrogen
sulfide (Chart 1).
pyrazolo[4,3-d]-1,2,4-triazolino[4,3-a]pyrimidin-3-yl)-
1,3-thiazol-4-yl]benzo-[f]-2H-chromen-3-one (11b),
respectively.
Formation of 11 can be explained via reaction of nitrile
imide 12, which formed in situ from hydrazonoyl
chlorides and triethylamine, with thiol isomer of 7 via 1,3-
addition to afford the thiohydrazonate ester 13, which
undergoes nucleophilic cyclization to yield 11.
Alternatively, 1,3-cyloaddition of nitrilimine to C=S
Treatment of
3
with the appropriate 2-aryl-1-
cyanoacrylonitrile 16a-c in boiling ethanol under reflux
containing catalytic amount of piperidine gave one
isolable product by evidence of which could be
formulated as 4-amino-6-aryl-3-(3-oxobenzo[f]chromen-
2-yl)-6,3a-dihydro-1,3-thiazolino[3,2-a]pyridine-5,7-

Nov-Dec 2008
Utility of 2-[4-(3-Oxobenzo[f]-2H-chromen-2-yl)-1,3-thiazol-2-yl]ethanenitrile
1721
Scheme 3
R
R
R
N
S
H2N
NC
N
S
CH2(CN)2
CN
N
S
+
Ar
3
ArCHO
+
3
NC
CN
Ar
CN
NC
Ar
16
NC
CN
Ar
18
19
17
a, Ar = C6H5
b, Ar = 4-CH3C6H4
c, Ar = 4-ClC6H4
R
R
COOC2H5
CN
Ar
N
S
+
3
O
N
S
+
Ar
19
NCCH2COOC2H5
C2H5OOC
CN
NH2
NC
CN
20
Ar
22
21
Scheme 4
R
R
R
DMF / KOH
PhNCS
CS2
N
S
N
S
N
S
DMF / KOH
CH3I
SK
NHPh
SCH3
CN
CN
3
CN
SH
27
+
H
R
R
N
S
S
S
XCH2Y
N
S
10a-c
CN
NHPh
R
N
CN
10a-c
S
NHPh
Ph
CN
SCH2Y
N
N
24
O
23
R'
S
R
NH2
Y
N
24,25a, Y = COOC2H5
b, Y = COCH3
c, Y = C6H5
26a, R' = OC2H5
b, R' = CH3
c, R' = C6H5
PhNH
S
d, Y = CN
e, Y = H
25(a-d)
dicarbonitrile 18a-c. Structure 18 was elucidated on the
basis of elemental analysis, spectral data and alternative
synthesis. The reaction seemed to proceed through
Michael addition reaction between 3 and 16 to give
intermediate 17, which underwent cyclization via addition
of NH hydrogen to nitrile function to give the final
product 18 (Scheme 3).
prepared via reaction of 3 with benzaldehyde (or reaction
of 1 with arylidenecyanothioacetamide [10]), with malo-
nonitrile in boiling ethanol containing catalytic amount of
piperidine gave a product identical in all respects (mp.
mixed mp. and spectra) with 18a.
Also, 3 was reacted with the appropriate 2-aryl-1-
cyanoacrylates 20a-c in boiling ethanol and piperidine to
afford 21a-c and not 22a-c on the base of spectral data
More evidence for structure 18 came from its
independent synthesis route by treatment of the
appropriate 3-aryl-2-[4-(3-oxobeno[f]-2H-chromen-2-yl)-
(1,3-thiazol-2-yl)]-3-prop-2-enenitrile 19a-c, which was
1
and analytical analyses. Thus, the HNMR spectrum of
21b showed signals at ꢀ = 2.32 (s, 3H, CH3) and 7.26 –
9.21 (m, 13H, ArH's) and no signals for ethoxy group. Its

1722
A. O. Abdelhamid and H. M. Abdelaziz
Vol 45
Compound 24a was converted to ethyl 3-amino-4-[4-
(3-oxobenzo[f]-2H-chromen-2-yl)(1,3-thiazol-2-yl)]-5-
phenylamino)-thiophene-2-carboxylate (25a) by boiling
in ethanol containing a catalytic amount of piperidine. All
the appropriate compounds 24b-d were boiled in ethanol
containing catalytically amount of piperidene to give the
corresponding thiophene derivatives 25b-d, respectively.
Also, treatment of 23 with the appropriate hydrazonyl
halides 10a-c in the presence of triethylamine afforded
2,3-dihydro-1,3,4-thiadiazoles 26a-c, respectively
(Scheme 4). Structure 26 was elucidated by elemental
analysis, spectral data and alternative synthesis. Thus,
methylcarbodithioate 27, which was prepared via reaction
of 3 with carbon disulfide in the presence of potassium
hydroxide followed by iodomethane, reacted with the
appropriate hydrazonoyl halides 10a-c to give products
identical in all respects (mp. mixed mp. and spectra) with
26a-c.
IR spectrum revealed bands at 2210 (CN), 1720, 1693
(CO's) and 1604 (C=C).
Furthermore, 3 was reacted with phenyl isothiocyanate
in N,N-dimethylformamide to afford a product which was
converted by hydrochloric acid to thioamide 23 (Scheme
4). Structure 23 was confirmed by elemental analysis,
spectral data and chemical transformation. Thus,
treatment of 23 with the appropriate ethyl chloroacetate,
chloroacetone, ꢀ-bromoacetophenone, chloroacetonitrile
and iodomethane to afford ethyl {2-cyano-2-[4-(3-oxo-
benzo[f]-2H-chromen-2-yl)(1,3-thiazol-2-yl)](phenylamino)-
vinylthio}-acetate (24a), 2-[4-(3-oxo-benzo[f]-2H-
chromen-2-yl)(1,3-thiazol-2-yl)-3-(2-oxopropylthio)-3-
(phenylamino)prop-2-enenitrile (24b), 2-[4-(3-oxobenzo-
[f]-2H-chromen-2-yl)(1,3-thiazol-2-yl)-3-(2-oxophenyl-
ethylthio)-3-(phenylamino)prop-2-enenitrile (24c),
3-(cyanoethylthio)2-[4-(3-oxobenzo[f]-2H-chromen-2-yl)-
(1,3-thiazol-2-yl)-3-phenylamino)prop-2-enenitrile (24d)
and 3-methylthio-2-[4-(3-oxobenzo[f]-2H-chromen-2-yl)-
(1,3-thiazol-2-yl)-3-(phenylamino)prop-2-enenitrile (24e)
respectively (Scheme 4).
Next, treatment of 24e with hydrazine hydrate in
boiling ethanol under reflux afforded 2-{2-[5-amino-3-
(phenylamino)pyrazol-4-yl]-1,3-thiazol-4-yl}benzo[f]-
Scheme 5
R
R
N
N
S
N
N
S
i- CH3COCH2COCH3
ii- CH3COCH2COOC2H5
iii- CH3COCH2CONHC6H5
iv- CH2(CN)2
H
N
CH3
PhNH
N
O
PhNH
N
N
R
R
CH3
CH3
29
30
N
S
N
N
S
PhCHO
SCH3
PhNH
N
CN
Ph
i
ii (or iii)
NHPh
CH2(CN)2
NH
24e
32
R
N
N
S
R
R
NH2NH2.H2O
PhNH
NH2
N
N
S
16a
N
S
NH
R
PhNH
NH2
CN
NH2
CN
PhNH
N
28
N
R
N
N
S
N
R
N
CN
20a
Ph
Ph
N
S
PhNH
NH2
35
COOC2H5
H
N
34
N
O
PhNH
CN
N
N
Ph
38
R
CN
39 Ph
N
N
S
N
N
S
H
Ph
PhNH
N
R
PhNH
N
Ph
R
N
NH
N
N
S
CN
CN
CN
N
S
NH2
Ph
PhNH
N
O
33
31
H
PhNH
N
Ph
N
CN
N
NH
COOC2H5
36
CN
37

Nov-Dec 2008
Utility of 2-[4-(3-Oxobenzo[f]-2H-chromen-2-yl)-1,3-thiazol-2-yl]ethanenitrile
1723
Table 1
Characterization data of the newly synthesized compounds.
Compound
Mp
Yield
%
Molecular
Formula
Analysis
%
Calcd./
Found
C
H
N
S
3
200-205
Dioxan
290-92
DMF
Brown
80
C18H10N2O2S
318.36
67.91
67.85
68.23
68.16
68.79
68.67
66.13
66.07
66.65
66.59
62.18
62.12
62.79
62.68
62.02
61.97
62.60
62.48
62.79
62.68
63.37
63.24
65.58
65.42
65.98
65.87
66.76
66.59
67.16
67.05
71.17
71.35
71.69
71.77
66.34
66.52
73.88
73.79
74.28
74.16
68.10
68.02
71.33
71.28
71.74
71.68
66.47
66.38
66.21
66.17
64.55
64.48
65.99
65.92
69.33
69.28
3.17
3.09
3.34
3.26
3.69
3.62
3.96
3.88
4.24
4.16
2.90
2.78
3.20
3.12
2.69
2.49
2.98
2.86
3.20
3.11
3.48
3.37
3.42
3.36
3.64
3.54
3.27
3.09
3.50
3.37
3.41
3.20
3.73
3.57
2.98
3.86
3.47
3.43
3.84
3.75
2.97
2.88
2.78
2.67
3.11
3.08
2.39
2.27
3.33
3.29
3.92
3.87
3.76
3.64
3.70
3.59
8.80
8.73
10.07
9.99
7.59
7.48
7.35
4a
Green
78
C24H14N4O2S
442.47
13.26
13.19
12.84
12.73
11.02
10.96
10.72
10.58
13.43
13.29
13.08
13.00
12.47
12.38
12.17
12.06
13.08
12.99
12.74
12.65
14.47
14.29
14.17
14.06
15.14
15.03
14.82
14.89
11.91
11.74
11.51
11.63
11.05
11.04
6.89
4b
285-86
DMF
Yellow
80
Brown
68
C25H16N4O2S
436.50
C28H20N4O4S
508.56
7.29
6.30
6a
170-72
Dioxan
258-60
Dioxan
243-45
Dioxan
250-52
DMF
6.27
6.14
6.03
6b
Brown
72
C29H22N4O4S
522.59
7a
Brown
68
Brown
68
C27H15N5O3S2
521.58
C28H17N5O3S2
535.61
12.29
12.26
11.97
11.78
11.42
11.37
11.14
11.07
11.97
11.88
11.67
11.62
4.73
7b
8a
233-35
Dioxan
242-45
Dioxan
198-200
Dioxan-EtOH
223-25
Dioxan-EtOH
185-87
Dioxan
223-25
Dioxan
200-202
DMF
Brown
68
C29H15N5O4S2
561
8b
Brown
65
Brown
72
C30H17N5O4S2
575.63
C28H17N5O3S2
535.61
9a
9b
Brown
65
C29H19N5O3S2
549.63
11a
11b
11c
11d
18a
18b
18c
19a
19b
19c
21a
Brown
69
Brown
75
C37H23N7O5S
677.70
C38H25N7O5S
691.73
7.64
4.64
4.57
4.95
4.88
4.85
Brown
68
C36H21N7O4S
647.68
>300
DMF
Brown
65
Gray
75
C37H23N7O4S
661.70
C28H16N4O2S
472.53
4.76
6.79
218-20
Dioxan
260-62
Dioxan
265-56
Dioxan
220-22
Dioxan-EtOH
255-57
Dioxan
235-37
Dioxan
224-42
Dioxan
245-46
Dioxan
230-32
Dioxan
185-86
EtOH
6.78
6.59
6.57
6.32
Yellow
80
C29H18N4O2S
486.58
Gray
78
Brown
80
C28H15ClN4O2S
506.97
C25H14N2O2S
406.47
6.28
7.89
6.75
6.66
6.57
6.35
7.77
7.63
7.57
7.27
Yellow
82
C26H16N2O2S
420.49
Yellow
85
Brown
75
C25H13ClN2O2S
440.91
C28H13N3O3S
471.33
6.30
8.91
7.16
6.80
8.85
8.65
8.59
8.31
8.27
9.26
9.19
7.79
7.68
8.25
8.19
7.35
6.72
6.60
6.45
6.34
21b
21c
23
Brown
80
Brown
78
Brown
68
Brown
75
Brown
65
Brown
69
C29H15N3O3S
485.53
C28H12ClN3O3S
505.94
C25H15N3O2S2
453.55
C29H21N3O4S2
539.64
C28H19N3O3S2
509.61
C33H21N3O3S2
571.68
6.27
14.14
14.06
11.88
11.75
12.58
12.45
11.22
11.17
24a
24b
24c
230-31
DMF-EtOH
260-62
EtOH
>300-301
Dioxan
7.24

1724
A. O. Abdelhamid and H. M. Abdelaziz
Vol 45
Table 1: Continued
Compound
Mp
Yield
%
Molecular
Formula
Analysis
%
Calcd./
Found
C
H
N
S
24d
24e
25a
25b
25c
25d
26a
26b
26c
27
185-87
DMF
250-52
DMF-EtOH
260-61
DMF
280-81
EtOH
>300
Dioxan
230-32
DMF
235-36
DMF-EtOH
235-37
DMF-EtOH
>300
Dioxan
257-260
DMF
>300
Dioxan
>300
DMF-EtOH
>300
Brown
60
Brown
75
Brown
68
Brown
65
Brown
68
Brown
60
Brown
95
Brown
95
Brown
69
Brown
79
Brown
70
Brown
65
Red
68
Brown
72
Black
68
C27H16N4O2S2
492.58
C26H17N3O2S2
467.57
C29H21N3O4S2
539.64
C28H19N3O3S2
509.68
C33H21N3O3S2
571.56
C27H16N4O2S2
492
C29H18N4O4S2
550.62
C28H16N4O3S2
520.50
C33H18N4O3S2
582.66
C20H12N2O2S2
408.52
C25H17N5O2S
451.51
C30H21N5O2S
515.60
C29H19N5O3S
517.57
C35H21N7O2S
603.62
C32H21N5O2S
539.62
C35H20N6O3S
604.65
65.84
65.75
66.79
66.69
64.55
64.47
65.99
65.86
69.33
69.26
65.84
65.79
63.26
63.18
64.60
64.48
68.03
67.98
58.80
58.73
66.50
66.45
69.89
69.85
67.30
67.21
69.64
69.59
71.23
71.16
69.52
69.47
3.27
3.19
3.66
3.59
3.92
3.87
3.76
3.74
3.70
3.61
3.27
3.15
3.30
3.25
3.10
3.25
3.11
3.08
2.96
2.88
3.80
3.74
4.11
4.07
3.70
3.58
3.51
3.43
3.92
3.85
3.33
3.26
11.37
11.32
8.99
8.77
7.79
7.62
8.25
8.18
7.35
13.02
12.96
13.72
13.63
11.88
11.76
12.58
12.39
11.22
11.17
13.02
12.98
11.65
11.58
12.32
12.48
11.01
10.96
23.55
23.41
7.10
7.30
11.37
11.35
10.18
10.06
10.76
10.56
9.62
9.58
6.86
6.75
15.51
15.47
13.58
13.42
13.53
13.49
16.24
16.13
12.98
12.77
13.90
13.86
28
6.98
6.22
6.17
6.20
6.18
5.31
5.19
5.94
29
30
AcOH
>300
DMF
245-46
Dioxan
>300
31
32
5.79
5.30
5.23
36
Brown
68
DMF
Table 2
Spectroscopic data of the newly synthesized compounds
Compound
Spectral data
IR: 3058, 2977 (CH), 2198 (CN), 1712 (CO) and 1596 (C=C)
3
1H NMR: 4.68 (s, 2H, CH2), 7.57-8.33 (m, 6H, ArH's), 8.44 (s, 1H, ArH) and 9.35 (s, 1H, ArH). .
IR: 3159 (NH), 2213 (CN), 1716, 1686 (CO) and 1596 (C=C)
4a
4b
6a
1HNMR: 7.40-8.64 (m, 12H), 9.36 (s, 1H) and 11.35 (s, 1H).
IR: 3132 (NH); 2218 (CN); 1720, 1639 (CO); 1616 (C=C).
1HNMR: 2.29 (s, 3H, CH3); 7.19- 9.36 (m, 11H, ArH's); 9.63 (s, 1H); 11.35 (s, 1H, NH).
IR: 3359, 3288 (NH2), 3136 (CH), 1720 (CO) and 1596 (C=C).
1HNMR: 1.16 (t, 3H, J = 7Hz, CH3CH2), 4.19 (q, 2H, J = 7Hz, CH3CH2), 6.04 (s, br, 2H, NH2), 7.27-8.67 (m,
12H, ArH's) and 9.49 (s, 1H, ArH).
6b
IR: 3483, 3413 (NH2); 3136 (CH aromatic); 2974 (CH aliphatic); 1720, 1639 (CO's); 1616 (C=C).
1HNMR: 1.25 (t, 3H, CH3CH2), 2.47 (s, 3H, CH3), 4.31(q, 2H, CH3CH2), 6.13 (s, br, 2H, NH2); 7.35- 9.60 (m,
12H, ArH's).
7a
7b
1HNMR: 7.40-8.64 (m, 12H, ArH's), 9.54 (s, 1H, ArH), 12.00 (s, 1H), and 13.95 (s, 1H).
IR: 3278 (NH); 1720(CO); 1620 (C=N).
1HNMR: 2.27 (s, 3H, CH3); 7.19- 9.56 (m, 12H, ArH's); 11.91 (s, 1H, NH); 13.95 (s, 1H, NH).
IR: 3136, 2981 (CH), 1725, 1674 (CO's) and 1596 (C=C).
1HNMR: 4.30 (s, 2H, CH2) and 7.38 - 9.48 (m, 12H, ArH's).
8a
8b
9a
9b
IR: 3136 (CH aromatic); 2923 (CH aliphtic); 1720, 1639 (CO's); 1616 (C=C).
1HNMR: 2.39 (s, 3H, CH3); 4.29 (s, 2H, CH2); 7.28- 9.54 (m,12H, ArH's)
IR: 3402 (NH); 3058 (CH aromatic); 1724, 1674 (CO's); 1596C=C).
1HNMR: 2.73 (s, 3H, SCH3); 7.40- 9.55 (m, 13H, ArH`s);12.01 (s, 1H, NH)
IR: 3413 (NH); 1720, 1639 (CO's); 1616 (C=C).
1HNMR: 2.36 (s, 3H, CH3); 2.66 (s, 3H, SCH3); 7.19- 9.36 (m, 12H, ArH's); 11.92 (s, 1H, NH).

Nov-Dec 2008
Utility of 2-[4-(3-Oxobenzo[f]-2H-chromen-2-yl)-1,3-thiazol-2-yl]ethanenitrile
1725
Table 2 (continued)
11a
11b
11c
11d
18a
18b
18c
19a
19b
21a
21c
23
IR: 3132, (CH aromatic); 2927 (CH aliphatic); 1720 (CO), 1624 (C=N); 1596 (C=C).
1HNMR: 1.25 (t, 3H, CH3CH2), 4.31(q, 2H, CH3CH2), 7.30- 9.55 (m, 13H, ArH`s and thiazole H-5).
IR: 3.056 (CH aromatic); 2993, 2974 (CH aliphatic); 1716, 1639 (C=O); 1616 (C=C).
1HNMR: 1.25 (t, 3H, CH3CH2), 2.35 (s, 3H, CH3), 4.31(q, 2H, CH3CH2), 7.19-9.48 (m, 17H, ArH`s)
IR: 3136, (CH aromatic); 2974, (CH aliphatic); 1720, 1639 (CO's).1616 (C=N).
1HNMR: 2.35 (s, 3H, CH3), 7.15- 9.36 (m, 18H, ArH`s).
IR: 1716, 1639 (CO's); 1616 (C=C).
1HNMR: 2.32 (s, 3H, CH3), 2.42 (s, 3H, CH3), 7.15- 9.36 (m, 17H, ArH`s).
IR: 3220, 3157 (NH2), 2194 (CN); 1716, (CO); 1594 (C=C).
1HNMR: 4.29 (s, 2H, NH2); 4.89 (s, 1H), 7.28-9.54 (m, 13H, ArH's)
IR: 3425 (NH), 2218 (CN), 1720, 1639 (CO's) and 1616 (C=N).
1HNMR: 2.39 (s, 3H, CH3), 4.29 (s, 2H, NH2), 4.82 (s, 1H) and 7.37 – 9.47 (m, 12H, ArH's).
IR: 3220, 3157 (NH2), 3036 (CH aromatic), 1720, 1639 (CO's), 1616 (C=C).
1HNMR: 4.29 (s, 2H, NH2), 4.89 (s, 1H), 7.28 - 9.54 (m, 12H, ArH's)
IR: 3136 (CH aromatic); 2198 (CN); 1716, (CO); 1593 C=C).
1HNMR: 7.35- 9.49 (m, ArH's)
IR: 3058 (CH aromatic); 2171 (CN); 1720 (CO); 1585 (C=C).
1HNMR: 2.37 (s, 3H, CH3); 7.34-9.41 (m, 13H, ArH's)
IR: 2194 (CN); 1716, 1684 (CO's); 1594 (C=C).
1HNMR: 7.28-9.54 (m, ArH's).
IR (KBr): 3136 (CH aromatic); 2923 (CH aliphtic); 1720, 1682 (CO's); 1616 (C=N).
1HNMR: 7.28 - 9.54 (m, ArH's).
IR: 3232 (NH), 2195 (CN), 1725 (C=O) and 1611 (C=C).
1HNMR: 7.21-9.54 (m, 13H, ArH's), 11.85 (s, 1H, NH) and 12.10 (s, 1H, SH).
1HNMR: 1.15 (t, 3H, CH3CH2), 3.60 (s, 2H, CH2), 4.08 (q, 2H, CH3CH2), 7.32 – 9.15 (m, 13H, ArH's) and
11.86 (s, br, 1H, NH).
IR: 3136 (CH aromatic); 2923 (CH aliphtic); 1720, 1716 (CO's); 1616 (C=N).
1HNMR = 2.28 (s, 3H, CH3), 5.69 (s, 2H, CH2), 7.51-9.29 (m, 12H, ArH`s) and 11.98 (s, 1H, NH).
IR: 3417 (NH aromatic); 2175 (CN); 1716; 1665 (CO's); 1616 (C=N).
1HNMR = 4.12 (s, 2H, CH2), 7.32- 9.12 (m, 18H, ArH's) and 11.87 (s, 1H, NH).
IR: 3425 (NH); 2923 (CH aliphatic); 2187 (CN); 1716 (CO); 1593 (C=C).
1HNMR: 4.70 (s, 2H, CH2); 7.46- 9.29 (m, 13H, ArH's); 12.03 (s, 1H, NH).
IR: 3402 (NH); 2912 (CH aliphatic); 2202 (CN); 1716, (CO).
24a
24b
24c
24d
24e
25a
1HNMR: 2.28 (s, 3H, SCH3); 7.51-9.30 (m, 13H, ArH`s); 11.98 (s, 1H, NH).
IR: 3420, 3321 (NH, NH2), 1716, 16243 (CO's), 1581 (C=C).
1HNMR:1.15 (t, 3H, CH3CH2), 4.08 (q, 2H, CH3CH2), 6.12 (s, br, 2H, NH2), 7.32 – 9.16 (m, 13H, ArH's) and
11.84 (s, br, 1H, NH).
25b
25c
25d
26a
26b
26c
27
IR: 3425, 3420 (NH2); 1716 (CO); 1593 (C=C).
1HNMR: 2.40 (s, 3H, CH3); 6.05 (s, br, 2H, NH2), 7.27- 9.49 (m, 13H, ArH's), 11.98 (s, 1H, NH).
IR: 3406, 3317 (NH2); 1716, 1727 (CO's); 1600 (C=C).
1HNMR: 6.05 (s, br, 2H, NH2), 7.27- 9.49 (m, 18H, ArH`s), 12.53 (s, 1H, NH).
IR: 2198 (CN); 1724, 1674 (CO's).
1HNMR: 6.11 (s, br, 2H, NH2), 7.32- 9.16 (m, 13H, ArH`s),11.83 (s, 1H, NH).
IR: 2198 (CN), 1743, 1716 (CO's), 1594 (C=C).
1HNMR: 1.15 (t, 3H, CH2CH3), 4.08 (q, 2H, CH2CH3), 7.14–9.63 (m, 13H, ArH's).
IR: 2923 (CH aliphtic); 2198 (CN); 1743, 1765 (CO's); 1593 (C=C).
1HNMR: 3.60 (s, 3H, CH3); 7.32- 9.16 (m, 13H, ArH`s).
IR: 2923 (CH aliphtic); 2198 (CN); 1743, 1700 (CO's); 1593(C=C).
1HNMR: 7.32- 9.16 (m, ArH`s).
IR: 2923 (CH aliphtic); 2198 (CN); 1743 (CO); 1593 (C=C).
1HNMR: 3.60 (s, 3H, CH3); 7.32- 9.16 (m, 8H, ArH`s); 11.87 (s, 1H, SH).
IR: 3506, 3317, 3285 (NH, NH2) 1716 (CO); 1594 (C=C).
28
1HNMR: 6.12 (s, br, 2H, NH2); 7.19- 9.3 (m, 13H, ArH`s); 11.87 (s, 1H, NH), 13.82 (s, 1H, NH).
IR: 3290 (NH), 1716, 1624 (CO's) and 1596 (C=C).
29
1HNMR: 2.35 (s, 3H, CH3), 2.39 (s, 3H, CH3), 7.57 – 9.35 (m, 14H, ArH's) and 11.98 (s, br, 1H, NH).
IR: 1716, 1664 (CO's); 1594 (C=C).
30
1HNMR: 2.39 (s, 3H, CH3), 3.98 (s, 2H, CH2), 7.27- 9.49 (m, 13H, ArH`s), 11.98 (s, 1H, NH)
IR: 2214 (CN), 1716, 1624 (CO's) and 1594 (C=C).
31
1HNMR: 6.12 (s, 2H, NH2), 7.32 - 9.16 (m, 18H, ArH's), 11.87 (s, br, 1H, NH).
IR: 1716, (CO); 1624 (C=N); 1593 (C=C).
32
1HNMR: 7.32- 9.16 (m, 19H, ArH`s), 11.86 (s, 1H, NH), 13.95 (s, 1H, NH).
IR: 2198 (CN); 1716 (CO); 1624 (C=N); 1593 (C=C).
36
1HNMR: 5.64 (s, 1H, pyrimidi9ne H-5), 7.27- 9.49 (m, 18H, ArH`s), 11.86 (s, 1H, NH).

1726
A. O. Abdelhamid and H. M. Abdelaziz
Vol 45
2H-chromen-3-one (28). Structure 28 was confirmed on
the basis of elemental analysis, spectral data and chemical
transformation. Thus, compound 28 was reacted with 2,4-
pentanedione in boiling acetic acid under reflux to afford
2-{2-[5,7-dimethyl-2-(phenylamino)-7a-hydropyrazolo-
[1,5-a]pyrimidin-3-yl]-1,3-thiazol-4-yl}benzo[f]-chromen-
3-one (29).
EXPERIMENTAL
All melting points were determined on an Electrothermal
apparatus and are uncorrected. The IR spectra are expressed in
cm-1 and recorded in KBr pellets on a Pa-9721 IR spectrometer.
1H NMR spectra were obtained on a Varian EM-390 (90) MHz
spectrometer in DMSO-d6 as solvent and TMS as internal
reference. Chemical shifts (ꢀ) are expressed in ppm. Mass
spectra were recorded on Kratos (75eV) MS equipment.
Elemental analysis was carried out at the Microanalytical Data
Unit at the National Research Center, Giza, Egypt. Hydrazonoyl
halides were prepared as previously methods [11-13].
2-[4-(3-Oxo-3H-benzo[f]chromen-2-yl)thiazol-2-yl)-1,3-
thiazol-2-yl]ethanenitrile (3). A mixture of 1 (3.17 g, 0.01mol)
and cyanothioacetamide (1 g, 0.01 mol) in ethanol (20 mL) was
refluxed for 3 hrs. The resulting solid was collected and washed
with boiling water containing sodium acetate then recrystallized
from dioxan-ethanol mixture to give 3 (tables 1and 2).
2-(2-Arylhydrazono)-2-(4-oxo-3H-benzo[f]chromen-2-yl)thi-
azol-2-yl)ethanenitrile 4a,b. Method (A). A mixture of 1 (3.17
g, 0.01mol) and the appropriate of arylazocyanothio-acetamide
(1.0 g, 0.01 mol) in ethanol (20 mL) was heated under reflux for
2 hrs. The resulting solid was collected, washed with boiling
water containing sodium acetate recrystallized from N,N-
dimethylformamide to give 4a and 4b, respectively (Tables 1
and 2).
Method (B). A solution of the appropriate aryldiazonium
chlorides (0.01 mol) was added to a solution of 3 (3.18 g, 0.01
mol) and sodium acetate (1.3 g, 0.01 mol) in ethanol (30 mL) at
0-5°C while stirring. The reaction mixture was stirred for 6 hrs
at 0°C; the resulting solid was collected and recrystallized from
N,N-dimethylformamide to give 4a and 4b, respectively (Tables
1 and 2)
Analogously, 2-{2-[5-amino-3-(phenylamino)pyrazol-
4-yl]-1,3-thiazol-4-yl}-benzo[f]-2H-chromen-3-one (28)
was reacted with ethyl 2-oxobutanoate in boiling acetic
acid to give one isolable product was formulated as: 2-{2-
[7-methyl-5-oxo-2-(phenylamino)-4,7a-hydropyrazolo-
[1,5-a]pyrimidin-3-yl]-1,3-thiazol-4-yl}benzo[f]chromen-
3-one (30). Structure 30 was elucidated by elemental
analysis, spectral data and alternative synthesis route.
Thus, treatment of 28 with acetoacenalide in boiling
acetic acid gave product identical in all respects (mp.
mixed mp. and spectra) with 30. Treatment of 28 with ꢀ-
cyanocinnamonitrile 16a in boiling ethanol containing
catalytic amounts of piperidine under reflux gave isolable
product evidence by mechanism which could be
formulated 7-amino-3-[4-(3-oxobenzo[f]-2H-chromen-2-
yl)(1,3-thiazol-2-yl)]-2-phenyl-amino-5-phenyl-7a-hydro-
pyrazolo[1,5-a]pyrimidine-6-carbonitrile (31) (Scheme 5).
The reaction seemed to proceed through Michael addition
reaction between 28 and 16a to give intermediate 33 or
34, which underwent cyclization via addition of the NH
hydrogen to the nitrile functional group followed by
autoxidation to give the final product 31 (Scheme 5).
More evidence for structure 31 came from its independent
synthesis, treatment of 2-{2-[5-(1-aza-2-phenylvinyl)-3-
phenylaminopyrazol-4-yl]-1,3-thiazo-4-yl}benzo[f]-2H-
chromen-3-one (32), which was prepared via reaction of
28 with benzaldehyde and malononitrile in boiling ethanol
containing catalytic amount of piperidine gave product
identical in all respects (mp. mixed mp. and spectra) with
31 (Scheme 5).
Ethyl 4-amino-1-aryl-3-[4-(3-oxo-3H-benzo[f]chromen-2-
yl)-1,3-thiazol-2-yl]-1H-pyrazole-5-carboxylate
6a,b.
A
mixture of the appropriate 4a, b (0.01 mol) and ethyl
chloroacetate (0.01 mol) in DMF (20 mL) containing anhydrous
potassium carbonate (0.01 mol) was refluxed in an oil bath at
130°C for 3 hrs. The mixture was cooled and triethylamine (1
mL) was added then the reaction mixture was refluxed for 1 h at
90°C. The reaction mixture was then poured over 100 mL of an
ice-water mixture. The resulting solid was collected and
recrystallized from dioxan to give 6a and 6b, respectively
(Tables 1 and 2).
Finally, ethyl ꢀ-cyanocinnamate was reacted with 20a
and 28 in boiling ethanol containing catalytic amount of
piperidine under reflux gave isolable product which could
be formulated 7-oxo-3-[4-(3-oxobenzo[f]-2H-chromen-2-
yl)(1,3-thiazol-2-yl)]-2-phenyl-amino-5-phenyl-6,7a-dihydro-
pyrazolo[1,5-a]pyrimidine-6-carbonitrile (36) (Scheme 5).
Also, treatment of 32, with ethyl cyanoacetate in
boiling ethanol containing catalytic amount of
piperidine under reflux to give product identical in all
respects (mp. mixed mp. and spectra) with 36 (Scheme
5). The reaction seemed to proceed through Michael
addition of the hydrogen from exocyclic amine to 28 to
give adduct intermediate 37 which underwent
cyclization to 38 via elimination of ethanol followed by
outoxidation to give the final product 36 via
elimination of ethanol.
1-Aryl-3-[4-(3-oxo-3H-benzo[f]chromen-2-yl)-1,3-thiazol-
2-yl]-5-thioxo-1,4,5,6-tetrahydro-7H-pyrazolo[4,3-d]pyrimid-
in-7-one 7a,b. A mixture of the appropriate 6a, b (0.01 mol) and
ammonium thiocyanate (0.76 g, 10 mmol) in acetic acid (20 mL)
containing hydrochloric acid (1 mL, 12 M) was heated under
reflux for 3 hrs. The reaction mixture was poured over ice (100
g). The resulting solid was collected and recrystallized from the
proper solvent to give 7a and 7b, respectively (Tables 1 and 2).
1-Aryl-3-[4-(3-oxobenzo[f]-2H-chromen-2-yl)(1,3-thiazol-
2-yl)]-7a-hydro-6H-pyrazolo[4,3-d]-1,3-thiazolino[3,2-a]-
pyrimidin-7,8-dione 8a,b and 1-aryl-2-[5-methylthio-7-oxo-6-
hydropyrazolo[4,5-d]pyrimidin-3-yl]-1,3-thiazol-4-yl)benzo-
[f]chromen-3-one 9a,b. A mixture of the appropriate 7a, b
(0.01 mol), potassium hydroxide (0.56 g, 0.01 mol) in N,N-
dimethylformamide (25 mL) was stirred for 4 hrs. The
appropriate ethyl chloroacetate (1.22 g, 0.01 mol) or
iodomethane (1.42 g, 0.01 mol) was added dropwise while
stirring to the above mixture and stirring was continued for 30

Nov-Dec 2008
Utility of 2-[4-(3-Oxobenzo[f]-2H-chromen-2-yl)-1,3-thiazol-2-yl]ethanenitrile
1727
min. The resulting solid was collected, washed with water and
recrystallized from dioxan to give 8a, 8b and 9a, 9b,
respectively (tables 1 and 2).
mL) was stirred for 4 hrs. The appropriate of ethyl chloroacetate,
chloroacetone, phenacyl bromide, chloroacetonitrile and
iodomethane (0.01 mol) was added dropwise while stirring to
the above mixture and stirring was continued for 30 min. The
resulting solid was collected, and recrystallized from proper
solvent to give 24a-e, respectively (Tables 1 and 2).
Ethyl 2-aryl-3-oxo-3[4-(3-oxobenzo[f]-2H-chormen-2-yl)-
(1,3-thiazol-2-yl)-1-phenyl-7a-hydropyrazolo[4,5-d]1,2,4-tria-
zolino[4,3-a]pyrimidine-7-carboxylate 11a,b. and 2-[2-(7-
Acetyl-2-aryl-3-oxo-5-phenyl-7a-hydropyrazolo[4,5-d]triazol-
ino[4,3-a]-pyrimidin-3-yl)-1,3-thiazol-4-yl]benzo[f]-2H-
chromen-3-one 11c, d. Equimolar amounts of each 7a and 7b,
the appropriate of hydrazonyl halides 10a,b and triethylamine
(0.01mol of each) in chloroform (20 mL) was refluxed for 10
hrs. The reaction mixture was evaporated under vacuum. The
resulting solid was collected and recrystallized from N,N-
dimethylformamide to give 11a-d respectively (Tables 1 and 2).
5-Amino-7-aryl-3-(3-oxobenzo[f]-2H-chromen-2-yl)-6,3a-
dihydro-1,3-thiazolino[3,2-a]pyridine-5,7-dicarbonitrile 18a-c
and 4-oxo-3-(3-oxobenzo[f]-2H-chromen-2-yl)-6-aryl-3a-
hydro-1,3-thiazolino[3,2-a]pyridine-5,7-dicarbonitrile 21a-c.
Method A. A mixture of 3 (3.18 g, 0.01 mol) and the
appropriate of 2-aryl-1-cyanoacrylonitrile derivatives 16a-c or 2-
arylacrylate derivatives 20a-c (0.01 mol) in ethanol (20 mL)
containing a catalytic amount of piperidine was refluxed for 4
hrs. The resulting solid was collected and recrystallized from
dioxan to give 18a-c and 21a-c, respectively (Tables 1 and 2).
Method B. A mixture of the appropriate of 19a-c (0.01 mol)
and malononitrile (or ethyl cyanoacetate) (0.01 mol) in ethanol
(20 mL) containing a catalytic amount of piperidine was
refluxed for 4 hrs. The resulting solid was collected and
recrystallized from dioxan to give 18a-c and 21a-c, respectively.
3-Aryl-2-[4-(3-oxobenzo[f]-2H-chromen-2-yl)(1,3-thiazol-
2-yl)]prop-2-enenitrile 19a-c. Method (A). A mixture of 1
(0.01 mol, 3.17 g) and the appropriate of ꢀ-arylidenecyanothio-
amide derivatives (0.01 mol) in ethanol (20 mL) was refluxed
for 2 hrs. The resulting solid was washed with boiling water
containing sodium acetate and recrystallized from dioxan to give
19a-c, respectively (Tables 1 and 2).
3-Amino-4-[4-(3-oxobenzo[f]-2H-chromen-2-yl)(1,3-thiazol-
2-yl)]-5-phenylamino)-2-substituted thiophenes 25a-d.
A
solution of the appropriate 24a-d (1 g) in ethanol (20 mL)
containing a catalytic amount of piperidine (3 drops) was heated
for 1 hour. The resulting solid was collected and recrystallized
from proper solvent to give 25a-d, respectively (Tables 1 and 2).
2-(3-Oxobenzo[f]-2H-chromen-2-yl)-3-(phenylamino)-3-
sulfanylprop-2-enenitrile (23). A mixture of 3 (3.18 g, 0.01
mol), potasium hydroxide (0.56 g, 0.01 mol) and phenyl
isothiocyanate (1.35 g, 0.01 mol) in N,N-dimethylformamide (25
mL) was stirred for 4 hrs. Iodomethane (1.42 g, 0.01 mol) was
added dropwise while stirring to the above mixture and stirring
was continued for 30 min. The resulting solid was acidified with
hydrochloric acid (3 M). The resulting solid was collected and
recrystallized from ethanol 23 (Tables 1 and 2).
2-(5-Acetyl-3-phenyl(1,3,4-thiadiazol-2-ylidene)-2-(4-(3-oxo-
benzo[f]-2H-chromen-2-yl)(1,3-thiazo-2-yl)ethanenitrile (26a),
ethyl 2-{cyano[(4-(3-oxobenzo[f]-2H-chromen-2-yl)(1,3-thiazo-
2-yl)methylene)-3-phenyl-1,3,4-thiadiazole-2-carboxylate (26b)
and 2-(5-benzoyl-3-phenyl(1,3,4-thiadiazol-2-ylidene)-2-(4-(3-
oxo-benzo[f]-2H-chromen-2-yl)(1,3-thiazo-2-yl ethanenitrile
(26c). Method (A). Triethylamine (0.75 ml, 0.005 mol) was
added to a mixture of 27 (0.005 mol) and the appropriate
hydrazonoyl halides10a-c (0.005 mol) in ethanol (15 mL) at
room temperature. The reaction mixture was stirred for 2 hrs.
The resulting solid was collected and recrystallized from proper
solvent to give 26a-c, respectively (tables 1 and 2).
Method (B). A mixture of 3 (3.18 g, 0.01 mol), potassium
hydroxide (0.56 g, 0.01 mol) and phenyl isothiocyanate (1.35 g,
0.01 mol) in N,N-dimethylformamide (15 mL) was stirred for 4
hrs. The appropriate of hydrazonoyl halides 10a-c (10 mmol)
was added portion-wise while stirring to the above mixture and
stirring was continued for 30 min. The resulting solid was
collected and recrystallized from proper solvent to give 26a-c,
respectively.
Method (B). A mixture of 20 (3.18 g, 0.01 mol) and the
appropriate of aromatic aldehyde (0.01 mol) in ethanol (20 mL)
containing a catalytic amount of piperidine was refluxed for 4
hrs. The resulting solid was collected and recrystallized from
dioxan to give 19a-c, respectively.
3-Methylthio-2-[4-oxobenzo[f]-2H-chromen-2-yl)(1,3-thia-
zol-2-yl)]-3-thioxopropanenitrile 27. A mixture of 3 (3.18 g,
0.01 mol), potassium hydroxide (0.56 g, 0.01 mol) and carbon
disulfide (0.76 g, 0.01 mol) in N,N-dimethylformamide (15 mL)
was stirred for 4 hrs. Iodomethane (1.52 g, 0.01 mol) was added
drop wise while stirring to the above mixture and stirring was
continued for 30 min. The resulting solid was collected, and
crystallized from N,N-dimethylformamide to give 27 (Tables 1
and 2).
Ethyl {2-cyano-2-[4-(3-oxobenzo[f]-2H-chromen-2-yl)(1,3-
thiazol-2-yl)](phenylamino)vinylthio}-acetate (24a), 2-[4-(3-
oxo-benzo[f]-2H-chromen-2-yl)(1,3-thiazol-2-yl)-3-(2-oxopro-
pylthio)-3-(phenylamino)prop-2-enenitrile (24b), 2-[4-(3-oxo-
benzo[f]-2H-chromen-2-yl)(1,3-thiazol-2-yl)-3-(2-oxophenyl-
ethylthio)-3-(phenylamino)prop-2-enenitrile (24c), 3-(cyano-
ethylthio)2-[4-(3-oxobenzo[f]-2H-chromen-2-yl)(1,3-thiazol-
2-yl)-3-phenylamino)prop-2-enenitrile (24d) and 3-methyl-
thio-2-[4-(3-oxobenzo[f]-2H-chromen-2-yl)(1,3-thiazol-2-yl)-
3-(phenylamino)-prop-2-enenitrile (24e). A mixture of 3 (3.18
g, 0.01 mol), potassium hydroxide (0.56 g, 0.01 mol) and phenyl
isothiocyanate (1.35 g, 0.01 mol) in N,N-dimethylformamide (25
2-{2-[5-Amino-3-(phenylamino)pyrazol-4-yl]-1,3-thiazol-4-
yl}benzo[f]-2H-chromen-3-one (28). A mixture of 24e (4.67 g,
0.01 mol) and hydrazine hydrate (1 mL, 99%) in ethanol (20
mL) was refluxed for 18 hrs, the solid product formed was
collected and recrystallized from N,N-dimethylformamide to
give 28 (tables 1 and 2).
3-{2-[5,7-Dimethyl-2-(phenylamino)-7a-hydropyrazolo-
[1,5-a]pyrimidin-3-yl]-1,3-thiazol-4-yl}benzo[f]-2H-chromen-
3-one (29) and 3-{2-[7-methyl-5-oxo-2-phenylamino]-4,7a-
dihydropyrazolo[1,5-a]pyrimidin-3-yl]-1,3-thiazol-4-yl}benzo-
[f]-2H-chromen-3-one (30). A mixture of 28 (4.51 g, 0.01 mol)
and the appropriate 2,4-pentanedione or ethyl 3-oxobutanoate
(or acetoacetanilide) (0.01 mol) in acetic acid (20 mL) was
boiled under refluxed for 3 hrs. The resulting solid was collected
and recrystallized from N,N-dimethylformamide to give 29 and
31, respectively (Tables 1 and 2).
7-Amino-3-[4-(3-oxo-benzo[f]-2H-chromen-2-yl)(1,3-thia-
zol-2-yl)-5-phenyl-2-(phenylamino)-7a-hydropyrazolo[1,5-a]-
pyrimidine-6-carbonitrile (31) and 7-oxo-3-[4-(3-oxobenzo[f]-
2H-chromen-2-yl)(-1,3-thiazol-2-yl)-5-phenyl-2-(phenylamino-
6,7a-dihydropyrazolo[1,5-a]pyrimidine-6-carbonitrile (36).

1728
A. O. Abdelhamid and H. M. Abdelaziz
Vol 45
[2] Tassies, D.; Freire, C. J. Monteagudo; Ordinas, A.; Reverter,
J.C. Haematolgica, 1992, 87, 1185
[3] Stone, W.B.; Okoniewski, J.C.; Stedelin, J.R. J. Wildlife Dis.
1999, 35, 187.
[4] Weick, J.; Thorn, R.S. J. Econ. Entomol, 2002, 95, 227.
[5] Mitscher, L.A. “Principles of Medicinal Chemistry” W. O.
Foye, T. L.Lemke and D. A. Williams, pp. 819-864, 5th ed. Williams and
Wikins, Baltimore, 2002.
[6] Lafitte,D.; V. Lamour, V.; Tsvetkov, P. O.; Makarov, A.A.;
Klich, M.; Deprez, P.; Moras, D.; Briand, C.; Gilli, R. Biochemistry
2002, 41, 7217.
[7] Kornis, D.I. Comperhensive Heterocyclic Chemistry, edited
by A. R. Katritzky, C. W. Ress and E. F. V. Scriven (Pergamon, Oxford,
1996), Vol. 4.
[8] Moustapha, C.; Abdel-Riheem, N.A.; Abdelhamid, A.O.
Synthetic Communication 2005, 35, 249.
Method (A). Equimolar amounts of 28 and the appropriate of 2-
phenyl-1-cyanoacrylonitrile derivatives 16a or ethyl 2-phenyl
acrylate (0.01 mol) in ethanol (20 mL) containing a catalytic
amount of piperidine was refluxed for 4 hrs. The resulting solid
was collected and recrystallized from DMF to give 31 and 36,
respectively (Tables 1 and 2).
Method (B). Equimolar amounts of 32 and malononitrile (or
ethyl cyanoacetate) (0.01 mol) in ethanol (20 mL) containing a
catalytic amount of piperidine was refluxed for 4 hrs. The
resulting solid was collected and recrystallized from N,N-
dimethylformamide to give 31 and 36, respectively.
3-{2-[5-(1-Aza-2-phenylvinyl)-3-(phenylamino)pyrazol-4-
yl)-1,3-thiazol-4-yl]-2H-benzo[f]chromen-3-one (32). Equimolar
amounts of 28 and benzaldehyde (0.01 mol) in ethanol (20 mL)
containing a catalytic amount of piperidene was refluxed for 3
hrs. The solid product formed was collected and recrystallized
from dioxan to give 32 (tables 1 and 2).
[9] Brunskill, J.S.A; De, A.; Ewing, O.F., J. Chem. Soc, Perkin
Trans I, 1978, 629.
[10] Broggiui, G.; Garanti, L.; Molteui, G.; Zecch, G.,
Tetrahedron 1988, 54, 2843.
REFERENCES
[11] Fravel, G.; Bull. Soc. Chim. Fr. 1904, 31, 150.
[12] Eweiss, N.E.; Osman, A. Tetrahedron Lett. 1979, 1169.
[13] Shawali, A.S.; Abdelhamid, A.O. Bull. Chem. Soc. Jpn.,
1976, 49, 321.
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