Synthesis of some oxazolyl - Pyrazolyl; 1,4-dihydropyridinyl-pyrazolyl and 1,2,3,4-tetrahydro pyrimidinyl-pyrazolyl coumarins

Article abstract of DOI:10.1002/jhet.5570450416

(Chemical Equation Presented) Various 3-[1-phenyl-4-(2-substituted-5-oxo- oxazol-4-ylidenemethyl) pyrazol-3-yl] coumarins 4a-f; 3-[1-phenyl-4-(2,6- dimethyl-3,5-disubstituted-1,4-dihydropyridin-4-yl) pyrazol-3-yl] coumarins 5a-f and 3-[1-phenyl-4-(6-methy

Full text of DOI:10.1002/jhet.5570450416

Jul-Aug 2008
1051
Synthesis of Some Oxazolyl - Pyrazolyl; 1,4-Dihydropyridinyl-
pyrazolyl and 1,2,3,4-Tetrahydro pyrimidinyl-pyrazolyl coumarins
Mehul A Patel and Dinker I Brahmbhatt*
Department of Chemistry, Sardar Patel University, Vallabh Vidyanagar - 388 120, Gujarat, India.
e-mail: drdibrahmbhatt@yahoo.co.in
Received June 12, 2007
R1
R1
O
O
N
O
O
O
CHO
R
R
N
N
O
N
N
Ph
Ph
R2
3a-c
4a-f
R1
CH3
R1
CH3
O
O
R2OC
O
O R2OC
NH
NH
R
CH3
R
N
H
O
N
COR2
N
N
N
Ph
Ph
5a-f
6a-f
Various 3-[1-phenyl-4-(2-substituted-5-oxo-oxazol-4-ylidenemethyl) pyrazol-3-yl] coumarins 4a-f;
3-[1-phenyl-4-(2,6-dimethyl-3,5-disubstituted-1,4-dihydropyridin-4-yl) pyrazol-3-yl] coumarins
5a-f and 3-[1-phenyl-4-(6-methyl-5-substituted-2-oxo-1,2,3,4-tetrahydropyrimidin-4-yl) pyrazol-
3-yl] coumarins 6a-f have been synthesized utilizing Erlenmyer-Plochl reaction, Hantzsch
reaction and Biginelli reaction respectively using 3-(1-phenyl-4-formyl-pyrazol-3-yl)
coumarins 3a-c as a starting material.
J. Heterocyclic Chem., 45, 1051 (2008).
INTRODUCTION
Considering the importance of pyrazole, oxazole, 1,4-
dihydropyridine and pyrimidine derivatives, it was
thought worthwhile to synthesize coumarin derivatives
having such nuclei as a substituent group and hence in the
present work various 3-[1-phenyl-4-(2-substituted-5-oxo-
oxazol-4-ylidenemethyl)pyrazol-3-yl] coumarins 4a-f; 3-
[1-phenyl-4-(2,6-dimethyl-3,5-disubstituted-1,4-dihydro-
pyridin-4-yl) pyrazol-3-yl] coumarins 5a-f and 3-[1-
phenyl-4-(6-methyl-5-substituted-2-oxo-1,2,3,4-tetra-
hydropyrimidin-4-yl) pyrazol-3-yl] coumarins 6a-f have
been synthesized utilizing Erlenmyer-Plochl reaction,
Hantzsch reaction and Biginelli reaction respectively
(Scheme 1).
Coumarins (2H-1-Benzopyran-2-ones) are well known
aromatic lactones isolated from a variety of plant sources
[1]. Owing to their diverse bioactivities viz. anticoagulant
[2], antibacterial and antifungal [3] etc. many natural,
semi synthetic and synthetic coumarins have become
important class of molecules in drug research. A large
number of coumarins having heterocyclic moieties like
benzimidazole, triazole, diazole, diazine, thiadiazole etc.
as a substituent group either in the lactone ring or in the
benzene ring of coumarin are used as dyes or whitening
agents [4]. Coumarins having nucleus like pyridine,
indole, triazole, oxazine as a substituent group possess a
variety of biological activities [5].
Pyrazole, oxazole, pyridine and pyrimidine are
prominent heterocyclic moieties and their derivatives
possess varied bioactivities. Certain pyrazole derivatives
[6] are reported to have antioxidant, anti-inflammatory,
antidepressant and antipyretic properties. Some oxazole
derivatives [7] possess bactericidal, antitumor and
antiarrhythmic properties. Certain 1,4-dihydropyridines
[8] are well known for their antihypertensive and anti-
inflammatory properties. Some pyrimidine derivatives [9]
are reported for their antitumor, antiviral and analgesic
properties.
The coumarinyl pyrazole aldehyde 3 was used as a
key aldehyde for the syntheses of compounds 4, 5 and
6. 3-Acetyl coumarins 1a-c were converted into their
corresponding phenyl hydrazones 2a-c. The phenyl
hydrazones 2a-c upon Vilsmeier-Haack reaction gave
the key aldehydes 3a-c. The aldehydes 3a-c on reaction
with N-acetylglycine or N-benzoylglycine in the
presence of sodium acetate and acetic anhydride gave 3-
[1-phenyl-4-(2-substituted-5-oxo-oxazol-4-ylidenemethyl)-
pyrazol-3-yl]coumarins 4a-f. The reaction of aldehydes
3a-c with acetyl acetone or ethyl acetoacetate under
Hantzsch reaction condition gave 3-[1-phenyl-4-(2,6-
dimethyl-3,5-disubstituted-1,4-dihydropyridin-4-yl)-

1052
M. A Patel and D. I Brahmbhatt
Vol 45
(0.01 mole), phenyl hydrazine (0.01 mole) and acetic acid (1.0
mL) in 50 mL of methanol was refluxed on water bath for 30
minutes. It was then allowed to come to room temperature. A
solid product separated out was collected by filtration, washed
with cold methanol, dried and recrystallized from ethanol.
Compound 2a. Yield 80%, mp 188 °C (lit [11] 188 °C).
Compound 2b. Yield 85%, mp 169 °C (lit [12] 170 °C).
Compound 2c. Yield 81%, mp 163 °C; ir: cm-1 3330, 3035,
pyrazol-3-yl] coumarins 5a-f. The Biginelli reaction of
aldehydes 3a-c using urea and acetyl acetone or ethyl
acetoacetate gave 3-[1-phenyl-4-(6-methyl-5-substi-
tuted-2-oxo-1,2,3,4-tetrahydro pyrimidin-4-yl)pyrazol-
3-yl] coumarins 6a-f.
The structures of the compounds 4, 5 and 6 were
established on the bases of analytical and spectral data.
The physical data of 4, 5 and 6 are shown in Table 1.
1
1723, 1603, 1245; H nmr: ꢀ 2.31 (3H, s, CH3), 3.99 (3H, s,
OCH3), 7.06-7.39 (8H, m, Ar-H), 7.60 (1H, s, NH, D2O
exchangeable), 8.05 (1H, s, C4-H of coumarin); 13C nmr: ꢀ
13.89(CH3), 56.26(OCH3), 113.29(CH), 113.34(CH),
119.82(CH), 120.21(C), 120.74(CH), 124.41(CH), 127.66(C),
129.33(CH), 139.05(C), 139.79(CH), 143.33(C), 144.53(C),
146.92(C), 160.02(CO). Anal. Calcd. for C18H16N2O3: C, 70.12;
H, 5.23; N, 9.09. Found: C, 70.10; H, 5.25; N, 9.10.
Synthesis of 3-(1-phenyl-4-formyl-pyrazol-3-yl) coumarins
3a-c. General Procedure. To a well stirred and cooled (0°C)
solution of coumarin phenyl hydrazones 2a-c (0.06 mole) in
anhydrous DMF (0.6 mole), POCl3 (0.18 mole) was added
dropwise during one hour. After complete addition of POCl3, the
reaction mixture was further stirred at 0 °C for one hour. After
the reaction mixture was heated at 65-70 °C for 2 hours it was
poured into crushed ice and left overnight in a refrigerator
EXPERIMENTAL
All the melting points reported are uncorrected. All ir spectra
(KBr disc) were recorded on Shimadzu FT-IR 8400-S
spectrometer. H nmr and 13C nmr spectra were recorded on a
Brucker Avance 400 spectrometer operating at 400 MHz for 1H
nmr and 100 MHz for 13C nmr. The chemical shift (ꢀ) is reported
in ppm using chloroform-d as a solvent and calibrated standard
solvent signal. Elemental analyses were carried out with a
Hareaus CHNO analyzer. 3-Acetyl coumarins 1a-c were
prepared according literature procedures [10].
1
Synthesis of coumarin phenyl hydrazones 2a-c. General
Procedure. A mixture of appropriate 3-acetyl coumarin 1a-c
Scheme 1
R1
R1
R1
O
O
O
O
O
N
O
O
N
Ph-NH-NH2
DMF
POCl3
AcOH, MeOH
CH3
CH3
CHO
R
R
R
NH
Ph
N
Ph
1a-c
2a-c
3a-c
a : R = R1 = H
b : R = Br, R1 = H
c : R = H, R1 = OCH3
R1
O
O
O
O
N
R2-CO-NH-CH2-COOH
AcONa, Ac2O
O
R
R
R
R2 = CH3 or Ph
N
O
N
Ph
R2
4a-f
R1
R1
CH3
O
O
N
O
R2OC
CH3-CO-CH2-CO-R2
AcONH4, AcOH
NH
R2 = CH3 or OEt
CHO
R
CH3
N
COR2
N
N
Ph
Ph
3a-c
5a-f
R1
CH3
NH
O
R2OC
CH3-CO-CH2-CO-R2
Urea, MeOH
R2 = CH3 or OEt
N
H
O
N
N
Ph
6a-f

Jul-Aug 2008
Synthesis of Some Oxazolyl - Pyrazolyl; 1,4-Dihydropyridinyl-pyrazolyl
and 1,2,3,4-Tetrahydro pyrimidinyl-pyrazolyl coumarins
1053
Table 1
Yield and melting point of 4a-f, 5a-f and 6a-f.
Comp.
R
R1
R2
Yield (%)
mp (°C)
Comp.
R
R1
R2
Yield (%)
mp (°C)
4a
4b
4c
4d
4e
4f
H
H
H
H
CH3
Ph
55
58
56
62
62
61
53
58
54
281-83
240-42
278-79
253-55
212-14
224-26
281-82
244-46
214-15
5d
5e
5f
Br
H
H
OCH3
OCH3
H
OEt
CH3
OEt
CH3
OEt
CH3
OEt
CH3
OEt
60
53
62
51
60
58
59
52
54
179-81
170-72
210-12
180-82
172-74
198-99
242-44
205-07
156-58
Br
Br
H
H
CH3
Ph
H
H
6a
6b
6c
6d
6e
6f
H
OCH3
OCH3
H
CH3
Ph
H
H
H
Br
Br
H
H
5a
5b
5c
H
CH3
OEt
CH3
H
H
H
OCH3
OCH3
Br
H
H
during which a solid product separated out, was collected by
filtration, washed with Na2CO3 (5%, 3 x 30 mL) and water. It
was then dried and recrystallized from ethanol.
as yellowish white solids, which were recrystallized from
chloroform-hexane.
1
Compound 4a. ir: cm-1 1725, 1720, 1600, 1430; H nmr: ꢀ
Compound 3a. Yield 78%, mp 215-16 °C; ir: cm-1 1723, 1689,
1603, 1407; 1H nmr: ꢀ 7.34-7.78 (9H, m, Ar-H), 8.24 (1H, s, C4-H
of coumarin), 8.54 (1H, s, C5’-H of pyrazole), 10.07 (1H, s, CHO);
13C nmr: ꢀ 116.80(CH), 119.02(C), 119.89(CH), 120.22(C), 124.03
(C), 124.84(CH), 128.22(CH), 128.56(CH), 129.78(CH), 130.94
(CH), 132.51(CH), 138.92(C), 143.15(CH), 147.80(C), 154.19(C),
160.16(CO), 185.23(CHO). Anal. Calcd. for C19H12N2O3: C, 72.15;
H, 3.82; N, 8.86. Found: C, 72.16; H, 3.85; N, 8.84.
Compound 3b. Yield 68%, mp 223-25 °C; ir: cm-1 1730,
1680, 1600, 1410; 1H nmr: ꢀ 7.27-7.84 (8H, m, Ar-H), 8.15 (1H,
s, C4-H of coumarin), 8.55 (1H, s, C5’-H of pyrazole), 10.06 (1H,
s, CHO); 13C nmr: ꢀ 115.16(C), 117.40(C), 118.31(CH),
118.53(CH), 119.87(CH), 120.52(C), 121.46(C), 124.05(C),
128.34(CH), 129.83(CH), 130.69(CH), 131.25(C), 135.18
(CH), 138.82(C), 141.58(CH), 152.97(CO), 184.94(CHO).
Anal.Calcd. for C19H11N2O3Br: C, 57.74; H, 2.81; N, 7.09.
Found: C, 57.76; H, 2.80; N, 7.12.
Compound 3c. Yield 66%, mp 240-41 °C; ir: cm-1 1726,
1683, 1608, 1395; 1H nmr: ꢀ 4.02 (3H, s, OCH3), 7.16-7.67 (8H,
m, Ar-H), 8.22 (1H, s, C4-H of coumarin), 8.54 (1H, s, C5’-H of
pyrazole), 10.06 (1H, s, CHO); 13C nmr: ꢀ 56.33(OCH3), 114.25
(CH), 119.64(C), 119.91(CH), 120.42(C), 124.06(C), 124.74
(CH), 128.22(CH), 129.79(CH), 130.81(CH), 138.93(CH),
141.60(CH), 143.34(C), 143.85(C), 147.18(C), 147.85(C),
159.68(CO), 185.39(CHO). Anal.Calcd. for C20H14N2O4: C,
69.36; H, 4.07; N, 8.09. Found: C, 69.38; H, 4.09; N, 8.08.
Synthesis of 3-[1-phenyl-4-(2-substituted-5-oxo-oxazol-4-
ylidene methyl) pyrazol-3-yl] coumarins 4a-f. General
Procedure. A mixture of appropriate 3-(1-phenyl-4-formyl-
pyrazol-3-yl) coumarins 3a-c (0.125 mole), N-acetylglycine
or N-benzoylglycine (0.125 mole), acetic anhydride (0.75
mole) and fused sodium acetate (0.125 mole) was warmed in
a water-bath till it became homogeneous solution (about 15-
20 minutes) and then it was heated for two hours in a boiling
water bath. After two hours heating, ethanol (30 mL) was
added in the reaction mixture and left overnight. The crude
solid obtained was extracted with chloroform (3 x 30 mL).
The chloroform extract was washed with water (3 x 20 mL)
and dried over anhydrous sodium sulfate. After removal of
chloroform under reduced pressure, the remaining residue was
purified by column chromatography using silica gel and ethyl
acetate - pet ether (60-80) (2:8) as an eluent. It afforded 4a-f
2.27 (3H, s, CH3), 7.07 (1H, s, methylylidene proton), 7.22-7.70
(9H, m, Ar-H), 8.03 (1H, s, C4-H of coumarin), 8.93 (1H, s, C5’-
H of pyrazole); 13C nmr: ꢀ 15.55(CH3), 116.54(CH), 117.17(C),
118.89(C), 119.61(CH), 120.20(C), 122.36(CH), 124.82(CH),
127.72(CH), 128.53(CH), 129.56(CH), 130.74(C), 131.63
(CH), 132.47(CH), 139.01(C), 143.89(CH), 148.75(C), 154.03
(C), 159.94(C), 164.89(CO of coumarin), 166.90(CO of
oxazolone). Anal.Calcd. for C23H15N3O4: C, 69.52; H, 3.80; N,
10.57. Found: C, 69.51; H, 3.81; N, 10.60.
1
Compound 4b. ir: cm-1 1725, 1723, 1610, 1405; H nmr: ꢀ
7.19-8.17 (15H, m, Ar-H and methylylidene proton merged),
8.53 (1H, s, C4-H of coumarin), 8.91 (1H, s, C5’-H of pyrazole);
13C nmr: ꢀ 110.87(C), 114.25(CH), 119.61(C), 119.88(CH),
119.95(C), 120.41(C), 124.68(CH), 124.73(CH), 127.67(CH),
127.85(CH), 128.19(CH), 128.91(CH), 129.67(CH),
129.69(CH), 129.77(CH), 130.82(CH), 138.88(C), 143.34
(CH), 143.82(C), 143.87(C), 143.92(C), 148.28(C), 157.85(CO
of coumarin), 164.73(CO of oxazolone). Anal. Calcd. for
C28H17N3O4: C, 73.20; H, 3.73; N, 9.15. Found: C, 73.22; H,
3.75; N, 9.17.
1
Compound 4c. ir: cm-1 1730, 1720, 1605, 1408; H nmr: ꢀ
2.31 (3H, s, CH3), 6.97 (1H, s, methylylidene proton), 7.17-7.74
(8H, m, Ar-H), 8.40 (1H, s, C4-H of coumarin), 8.89 (1H, s, C5’-
H
of pyrazole); 13C nmr:
ꢀ 14.32(CH3), 114.61(CH),
119.41(CH), 119.88(CH), 119.95(C), 120.68(C), 124.37(CH),
124.67(CH), 127.15(CH), 127.89(C), 128.25(CH), 128.91(C),
129.69(CH), 129.77(C), 129.82(C), 130.88(CH), 138.34(C),
143.67(C), 143.82(C), 161.87(CO of coumarin), 167.32(CO of
oxazolone). Anal. Calcd. for C23H14N3O4Br: C, 58.00; H, 2.96;
N, 8.82. Found: C, 57.98; H, 3.00; N, 8.80.
1
Compound 4d. ir: cm-1 1728, 1720, 1598, 1412; H nmr: ꢀ
7.17-8.05 (14H, m, Ar-H and methylylidene proton merged),
8.51 (1H, s, C4-H of coumarin), 9.05 (1H, s, C5’-H of pyrazole);
13C nmr: ꢀ 114.14(C), 116.50(CH), 117.16(C), 118.82(C),
119.62(C), 120.24(CH), 122.37(CH), 124.89(CH), 127.71
(CH), 128.53(CH), 129.56(CH), 130.74(CH), 131.69(CH),
132.43(C), 139.04(C), 143.89(CH), 148.75(C), 154.03(C),
159.97(C), 164.81(CO of coumarin), 165.90(CO of
oxazolone). Anal. Calcd. for C28H16N3O4Br: C, 62.47; H, 3.00;
N, 7.81. Found: C, 62.50; H, 2.98; N, 7.84.
1
Compound 4e. ir: cm-1 1723, 1720, 1607, 1400; H nmr: ꢀ
2.51 (3H, s, CH3), 3.93 (3H, s, OCH3), 7.34-8.11 (9H, m, Ar-H

1054
M. A Patel and D. I Brahmbhatt
Vol 45
and methylylidene proton merged), 8.40 (1H, s, C4-H of
coumarin), 9.30 (1H, s, C5’-H of pyrazole); 13C nmr: ꢀ
15.55(CH3), 56.20(OCH3), 116.89(CH), 117.61(C), 118.20(C),
119.36(CH), 120.82(C), 122.72(CH), 124.53(CH), 127.56(C),
128.54(CH), 129.74(CH), 130.63(CH), 131.47(C), 132.01
(CH), 139.89(C), 143.75(CH), 148.03(C), 154.94(C), 159.90
(C), 164.89(CO of coumarin), 167.17 (CO of oxazolone). Anal.
Calcd. for C24H17N3O5: C, 67.44; H, 4.01; N, 9.83. Found: C,
67.45; H, 3.99; N, 9.85.
126.64(CH), 128.02(C), 128.41(CH), 129.26(CH), 131.61(C),
139.92(C), 142.68(CH), 144.21(C), 145.52(C), 153.96(C),
160.23(CO of coumarin), 167.45 (COOEt). Anal. Calcd. for
C31H29N3O6: C, 69.00; H, 5.42; N, 7.79. Found: C, 69.03; H,
5.43; N, 7.80.
1
Compound 5c. ir: cm-1 3300, 1725, 1680, 1605, 1435; H
nmr: ꢀ 2.14 (6H, s, 2 x Ar-CH3), 2.38 (6H, s, 2 x -COCH3), 5.18
(1H, s, methine proton), 5.38 (1H, s, NH proton, D2O
exchangeable), 7.27-7.83 (8H, m, Ar-H), 7.92 (1H, s, C4-H of
coumarin), 8.04 (1H, s, C5’-H of pyrazole); 13C nmr: ꢀ
1
Compound 4f. ir: cm-1 1729, 1723, 1613, 1405; H nmr: ꢀ
4.01 (3H, s, OCH3), 7.17-8.21 (14H, m, Ar-H and methylylidene
proton merged), 8.53 (1H, s, C4-H of coumarin), 9.16 (1H, s,
C5’-H of pyrazole); 13C nmr: ꢀ 56.32(OCH3), 109.87(C), 114.25
(CH), 119.61(C), 119.88(CH), 119.95(C), 120.41(C),
124.68(C), 124.73(CH), 127.67(CH), 127.85(CH), 128.19
(CH), 128.91(CH), 129.67(C), 129.69(CH), 129.77(CH),
130.82(CH), 138.88(C), 143.34(CH), 143.82(C), 143.87(C),
143.92(C), 160.82(CO of coumarin), 167.92(CO of
oxazolone). Anal. Calcd. for C29H19N3O5: C, 71.16; H, 3.91; N,
8.58. Found: C, 71.20; H, 3.95; N, 8.57.
18.93(CH3),
30.09(-COCH3),
30.99(C4”),
113.95(CH),
118.63(C), 120.18(CH), 121.93(CH), 125.40(CH), 126.04(CH),
128.60(CH), 130.88(C), 131.98(C), 132.36(CH), 138.60(C),
141.71(C), 142.70(CH), 143.71(C), 145.57(C), 147.80(C),
162.47(CO of coumarin), 195.95(COCH3). (Here there was
deficiency of one 13C signal, which may be due to identical
chemical shift of two carbon atoms.) Anal. Calcd. for
C29H24N3O4Br: C, 62.37; H, 4.33; N, 7.52. Found: C, 62.38; H,
4.31; N, 7.51.
Compound 5d. ir: cm-1 3310, 1765, 1720, 1605, 1443; H
1
In case of the compounds 4d and 4f, the numbers of
carbon signals in 13C NMR spectra were less than expected
which may be due to identical chemical shift of certain carbons.
Synthesis of 3-[1-phenyl-4-(2,6-dimethyl-3,5-disubstituted-
1,4-dihydropyridin-4-yl) pyrazol-3-yl] coumarins 5a-f.
General Procedure. A mixture of appropriate 3-(1-phenyl-4-
formyl-pyrazol-3-yl) coumarin 3a-c (0.01 mole), acetyl acetone
or ethyl acetoacetate (0.02 mole) and ammonium acetate (2.0 g)
in 50 mL of acetic acid was stirred for 10 minutes at room
temperature and then refluxed in an oil bath at 130 °C for 12
hours. It was allowed to come to room temperature and was left
overnight. The reaction mixture was poured into ice-cold water.
Then it was extracted with ethyl acetate (3 x 30 mL). The ethyl
acetate extract was then washed with water (3 x 20 mL) and
dried over anhydrous sodium sulfate. Removal of ethyl acetate
under reduced pressure resulted in a crude solid which was
further purified by column chromatography using silica gel and
ethyl acetate - pet ether (60-80) (2:8) as an eluent to afford
compounds 5a-f as yellowish white solids, which were
recrystallized from chloroform-hexane.
nmr: ꢀ 1.16 (6H, t, 2 x -COO CH2CH3), 2.16 (6H, s, 2 x Ar-
CH3), 3.63 (4H, q, 2 x -COOCH2CH3), 5.29 (1H, s, methine
proton), 5.72 (1H, s, NH proton, D2O exchangeable), 7.32-7.78
(8H, m, Ar-H), 7.98 (1H, s, C4-H of coumarin), 8.04 (1H, s, C5’-
H of pyrazole); 13C nmr: ꢀ 14.53(CH3), 18.95(-COOCH2CH3),
30.29 (C4”), 59.07(-COOCH2CH3), 106.37(CH), 118.48(C),
119.90(CH), 120.38(C), 121.96(CH), 123.99(C), 126.33(C),
126.64(CH), 127.02(CH), 128.26(C), 128.41(CH),
130.61(CH), 140.29(C), 141.68(C), 142.21(CH), 144.52(C),
152.96(C), 160.96(CO of coumarin), 168.23(COOEt). Anal.
Calcd. for C31H28N3O6Br: C, 60.20; H, 4.56; N, 6.79. Found: C,
60.23; H, 4.58; N, 6.80.
1
Compound 5e. ir: cm-1 3301, 1729, 1675, 1615, 1448; H
nmr: ꢀ 2.15 (6H, s, 2 x Ar-CH3), 2.29 (6H, s, 2 x -COCH3), 3.99
(3H, s, OCH3), 5.41 (1H, s, methine proton), 5.96 (1H, s, NH
proton, D2O exchangeable), 7.10-7.65 (8H, m, Ar-H), 7.74 (1H,
s, C4-H of coumarin), 7.77 (1H, s, C5’-H of pyrazole); 13C nmr: ꢀ
20.08(CH3), 30.14(-COCH3), 30.87(C4”), 56.21(OCH3),
112.85(CH), 113.66(C), 119.14(CH), 119.69(CH), 119.87(C),
123.23(CH), 124.45(CH), 126.53(C), 126.95(CH), 127.29(C),
129.32(CH), 139.73(C), 142.91(C), 142.97(CH), 143.58(C),
145.47(C), 147.01(C), 160.11(CO of coumarin), 198.06
(COCH3). Anal. Calcd. for C30H27N3O5: C, 70.71; H, 5.34; N,
8.25. Found: C, 70.69; H, 5.36; N, 8.26.
1
Compound 5a. ir: cm-1 3305, 1723, 1680, 1605, 1440; H
nmr: ꢀ 2.17 (6H, s, 2 x Ar-CH3), 2.31 (6H, s, 2 x -COCH3), 5.43
(1H, s, methine proton), 5.64 (1H, s, NH proton, D2O
exchangeable), 7.31-7.67 (9H, m, Ar-H), 7.73 (1H, s, C4-H of
coumarin), 7.80 (1H, s, C5’-H of pyrazole); 13C nmr: ꢀ 19.43(2 x
CH3), 29.30(2 x -COCH3), 30.62(C4”), 112.05(C), 116.63(CH),
118.51(C), 119.43 (CH), 122.90(CH), 125.04(CH), 126.60
(CH), 128.88(CH), 129.95(CH), 132.36(CH), 136.00(C),
139.71(C), 141.70(C), 142.71(CH), 143.50(C), 145.08(C),
160.07(CO of coumarin), 196.65(COCH3). (Here there was
deficiency of one 13C signal, which may be due to identical
chemical shift of two carbon atoms.) Anal. Calcd. for
C29H25N3O4: C, 72.64; H, 5.25; N, 8.76. Found: C, 72.66; H,
5.27; N, 8.79.
1
Compound 5f. ir: cm-1 3301, 1768, 1723, 1612, 1441; H
nmr: ꢀ 1.23 (6H, t, 2 x –COO CH2CH3), 2.15 (6H, s, 2 x Ar-
CH3), 3.99 (3H, s, OCH3), 4.07 (4H, q, 2 x -COOCH2 CH3), 5.33
(1H, s, methine proton), 5.75 (1H, s, NH proton, D2O
exchangeable), 7.16-7.66 (8H, m, Ar-H), 7.79 (1H, s, C4-H of
coumarin), 7.89 (1H, s, C5’-H of pyrazole); 13C nmr: ꢀ
15.07(CH3), 19.85(-COOCH2CH3), 30.57(C4”), 56.62(OCH3),
60.92(-COOCH2CH3), 108.87(CH), 116.84(CH), 119.83 (CH),
120.06(C), 122.69(CH), 124.64(C), 126.33(C), 126.46 (CH),
128.19(C), 128.21(C), 129.92(CH), 131.61(CH), 140.02 (C),
142.89(CH), 144.21(C), 145.52(C), 155.06(C), 160.63(CO of
coumarin), 166.95(COOEt). Anal. Calcd. for C32H31N3O7: C,
67.48; H, 5.49; N, 7.38. Found: C, 67.50; H, 5.50; N, 7.40.
Synthesis of 3-[1-phenyl-4-(6-methyl-5-substituted-2-oxo-
1,2,3,4-tetrahydropyrimidin-4-yl) pyrazol-3-yl] coumarins
6a-f. General Procedure. A mixture of appropriate 3-(1-
phenyl-4-formyl-pyrazol-3-yl) coumarin 3a-c (0.01 mole),
acetyl acetone or ethyl acetoacetate (0.01 mole), urea (0.01
1
Compound 5b. ir: cm-1 3310, 1760, 1728, 1600, 1445; H
nmr: ꢀ 1.22 (6H, t, 2 x -COOCH2CH3), 2.15 (6H, s, 2 x Ar-CH3),
4.08 (4H, q, 2 x -COOCH2CH3), 5.23 (1H, s, methine proton),
5.66 (1H, s, NH proton, D2O exchangeable), 7.26-7.67 (9H, m,
Ar-H), 7.81 (1H, s, C4-H of coumarin), 7.89 (1H, s, C5’-H of
pyrazole); 13C nmr: ꢀ 14.37(CH3), 19.55(-COOCH2CH3), 30.07
(C4”), 59.92(-COOCH2CH3), 102.77(C), 116.48(CH), 119.09
(C), 119.38(CH), 122.96(CH), 124.46(CH), 126.33(CH),

Jul-Aug 2008
Synthesis of Some Oxazolyl - Pyrazolyl; 1,4-Dihydropyridinyl-pyrazolyl
and 1,2,3,4-Tetrahydro pyrimidinyl-pyrazolyl coumarins
1055
mole) and concentrated hydrochloric acid (0.5 mL) in 50 mL
methanol was stirred for 10 minutes at room temperature and
then refluxed on a water bath for 8 hours. On cooling, a crude
solid product separated out which was collected by filtration,
washed with water and purified by column chromatography
using silica gel and ethyl acetate-pet ether (60-80) (2:8) as an
eluent. It afforded 6a-f as white solids, which were
recrystallized from chloroform-hexane.
19.99(CH3),
29.93(-COCH3),
30.03(C4”),
56.30(OCH3),
113.28(CH), 118.84(CH), 118.98(CH), 120.42(C), 124.07(CH),
124.77(CH), 128.27(CH), 129.79(C), 130.87(C), 134.79(C),
136.81(C), 138.93(CH), 142.93(CH), 143.34(C), 143.85(C),
147.18(C), 147.85(C), 159.68(CO at C2”), 160.05(CO of
coumarin), 198.18(COCH3). Anal. Calcd. for C26H22N4O5: C,
66.37; H, 4.71; N, 11.91. Found: C, 66.36; H, 4.70; N, 11.94.
Compound 6f. ir: cm-1 3307, 1726, 1682, 1608, 1443; H
1
1
Compound 6a. ir: cm-1 3308, 1725, 1683, 1610, 1443; H
nmr: ꢀ 1.22(3H, t, -COOCH2 CH3), 2.19(3H, s, Ar-CH3), 3.89
(3H, s, OCH3), 3.97(2H, q, -COOCH2CH3), 5.40(1H, s, methine
proton), 7.09-7.65 (10H, m, eight Ar-H and two NH protons
merged), 7.76 (1H, s, C4-H of coumarin), 7.90(1H, s, C5’-H of
pyrazole); 13C nmr: ꢀ 19.87(CH3), 30.18(-COO CH2CH3),
30.57(C4”), 56.21(OCH3), 60.01(-COOCH2CH3), 112.88(CH),
113.68(C), 119.14 (CH), 119.69(CH), 119.87(C), 123.28(CH),
124.45(CH), 126.53(C), 127.15(C), 127.29(C), 129.32(CH),
139.72(CH), 142.92(CH), 142.97(C), 143.58(C), 145.47(C),
147.01(C), 157.81(CO at C2”), 160.11(CO of coumarin),
168.18(COOEt). Anal. Calcd. for C27H24N4O6: C, 64.79; H,
4.83; N, 11.19. Found: C, 64.80; H, 4.82; N, 11.20.
nmr: ꢀ 2.14 (3H, s, Ar-CH3), 2.29 (3H, s, -COCH3), 5.39(1H, s,
methine proton), 7.09-7.64 (11H, m, nine Ar-H and two NH
protons merged), 7.84 (1H, s, C4-H of coumarin), 8.00 (1H, s,
C5’-H of pyrazole); 13C nmr: ꢀ 19.98(CH3), 30.19(-COCH3),
30.67(C4”), 113.83(CH), 114.66 (C), 118.94(CH), 119.97(CH),
123.35(C), 124.45(CH), 126.53(CH), 126.97(CH), 127.29(C),
129.37(CH), 139.73(CH), 142.91(CH), 142.99(C), 143.78(C),
145.49(C), 147.10(C), 158.17 (CO at C2”), 160.11(CO of
coumarin), 197.96 (-COCH3). (Here there was deficiency of one
13C signal, which may be due to identical chemical shift of two
carbon atoms.) Anal. Calcd. for C25H20N4O4: C, 68.17; H, 4.58;
N, 12.72. Found: C, 68.20; H, 4.60; N, 12.70.
Acknowledgement. The authors are thankful to the Head,
Department of Chemistry, Sardar Patel University for providing
research facilities. The authors are also thankful to Vaibhav
Laboratories, Shahibaug, Ahmedabad for IR spectral analysis.
1
Compound 6b: ir: cm-1 3310, 1725, 1685, 1610, 1445; H
nmr: ꢀ 1.21(3H, t, -COOCH2 CH3), 2.16 (3H, s, Ar-CH3), 3.99
(2H, q, -COOCH2CH3), 5.40 (1H, s, methine proton), 7.08-7.55
(11H, m, nine Ar-H and two NH protons merged), 7.69 (1H, s,
C4-H of coumarin), 7.86 (1H, s, C5’-H of pyrazole); 13C nmr: ꢀ
14.57(CH3), 19.53(-COOCH2CH3), 30.37(C4”), 58.92(-
COOCH2CH3), 108.67(C), 116.46(CH), 119.09(CH), 119.38
(CH), 122.96(C), 124.46(CH), 126.33(CH), 126.64(CH),
128.02(C), 128.49(C), 129.26(CH), 131.61(C), 139.99(CH),
142.69(C), 144.21(CH), 145.52(C), 153.96(C), 158.86(CO at
C2”), 160.20(CO of coumarin), 167.02(COOEt). Anal. Calcd.
for C26H22N4O5: C, 66.37; H, 4.71; N, 11.91. Found: C, 66.39; H,
4.70; N, 11.92.
Compound 6c. ir: cm-1 3315, 1720, 1690, 1615, 1435; 1H nmr: ꢀ
2.15 (3H, s, Ar-CH3), 2.17 (3H, s, -COCH3), 5.31 (1H, s, methine
proton), 7.12-7.78 (10H, m, eight Ar-H and two NH protons
merged), 7.80 (1H, s, C4-H of coumarin), 7.89 (1H, s, C5’-H of
pyrazole); 13C nmr: ꢀ 20.84(CH3), 29.04(-COCH3), 30.94(C4”),
114.37(CH), 119.67(C), 119.77(CH), 119.90(CH), 120.40(C),
124.51(C), 124.75(CH), 127.43(C), 127.93(CH), 128.22(C),
129.59(CH), 129.79(CH), 130.86(C), 138.91(C), 142.75(CH),
143.37(C), 147.17(C), 158.36(CO at C2”), 168.63 (CO of coumarin),
195.43(COCH3). Anal. Calcd. for C25H19N4O4Br: C, 57.82; H, 3.69;
N, 10.79. Found: C, 57.85; H, 3.70; N, 10.78.
REFERENCES
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Compound 6d. ir: cm-1 3315, 1720, 1675, 1608, 1435; 1H nmr:
ꢀ 1.17(3H, t, -COOCH2 CH3), 2.15 (3H, s, Ar-CH3), 3.67 (2H, q, -
COOCH2CH3), 5.30 (1H, s, methine proton), 7.12-7.80 (10H, m,
eight Ar-H and two NH protons merged), 7.89 (1H, s, C4-H of
coumarin), 8.06 (1H, s, C5’-H of pyrazole); 13C nmr: ꢀ 14.08(CH3),
19.98(-COOCH2CH3),
29.02(C4”),
60.06(-COOCH2CH3),
109.80(C), 116.80(CH), 119.02(C), 119.89 (CH), 120.22(C),
124.23(C), 124.82(CH), 128.26(CH), 128.52 (CH), 129.78(CH),
130.98(C), 132.58(C), 138.82(CH), 143.18 (CH), 143.68(C),
147.80(C), 150.08(C), 156.69(CO at C2”) 160.06(CO of
coumarin), 164.10(COOEt). Anal. Calcd. for C26H21N4O5Br: C,
56.84; H, 3.85; N, 10.20. Found: C, 56.86; H, 3.87; N, 10.22.
1
Compound 6e. ir: cm-1 3312, 1728, 1683, 1615, 1438; H
nmr: ꢀ 2.13 (3H, s, Ar-CH3), 2.39 (3H, s, -COCH3), 4.09 (3H, s,
OCH3), 5.45 (1H, s, methine proton), 7.06-7.64 (10H, m, eight
Ar-H and two NH protons merged), 7.75 (1H, s, C4-H of
coumarin), 7.78 (1H, s, C5’-H of pyrazole); 13C nmr: ꢀ
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