Pyranopyrazoles III synthesis of 1H-pyrano[2,3-c]pyrazol-4-ones [1]

Article abstract of DOI:10.1002/jhet.5570380129

Various derivatives of title ring system were synthesized by Claisen condensation of 4 acetyl-5-hydroxypyrazoles with appropriate esters, followed by acid-catalyzed ring closure.

Full text of DOI:10.1002/jhet.5570380129

Jan-Feb 2001
Pyranopyrazoles III Synthesis of 1H-Pyrano[2,3-c]pyrazol-4-ones [1]
193
Misbahul Ain Khan* [a,b], Gwynn Pennant Ellis [c] and Mario Celso Pagotto [b,d]
[a] Laboratorio de Quimica Medicinal, Faculdade de Farmacia,
Universidade Federal Fluminense, Santa Rosa, Niteroi, RJ, 24230-000, Brasil
[b] Secao de Quimica, Instituto Militar de Engenharia, Praia Vermelha, Rio de Janeiro, RJ, Brasil
[c] Department of Chemistry, University of Wales Institute of Science and Technology, Cardiff, Wales, UK
[d] Liquid Quimica, Estrada Sr. Rene Fonseca, s/n, Cubatao, SP, 11573-904, Brasil
Received July 10, 1999
Various derivatives of title ring system were synthesized by Claisen condensation of 4 acetyl-5-hydroxy-
pyrazoles with appropriate esters, followed by acid-catalyzed ring closure.
J. Heterocyclic Chem., 38, 193 (2001).
Replacement of the benzene ring in coumarin and
when heated with acetic anhydride and sodium acetate [8]
furnished the respective 4-acetyl-5-hydroxypyrazoles
(7-10). The infrared and H-nmr spectra support the
chromone by a pyrazole ring can lead to the heterocyclic
isosteric systems 1H-pyrano[2,3-c]pyrazol-6-one (1) and
1H-pyrano[2,3-c]pyrazol-4-one (2) respectively. While 1
has been mentioned in the literature and various of its
derivatives and their reactions have been described [1], not
much is known about 2 except a few attempts at the syn-
thesis of this system as reported by Heinish et al., and
Gelin et al. [2]. Previously, we communicated the
synthesis of this system (2) [3] and now would like to
report in detail the synthesis of various derivatives of (2).
The starting material, pyrazolones (3-6), were prepared
according to literature methods [4-7] by reaction of the
appropriate hydrazines with β-ketoesters. These pyrazolones
1
tuatomeric ''4-acetyl-5-hydroxypyrazoles'' structures. The
infrared spectra displayed a strong hydrogen-bonded
-1
carbonyl absorption in the region 1640-1620 cm and a
weak and broad hydroxyl absorption between 3270-3100
-1
1
cm . In the H-nmr spectra one proton singlet in a low
magnetic field (δ 10.30-12.85) was observed for 7-9 which
could be ascribed to the hydroxyl proton. For 10, however,
this proton was observed at δ 7.05.
A Claisen condensation of these hydroxypyrazoles with
the appropriate esters in the presence of base (sodium
ethoxide for diethyl oxalate and sodium hydride
H
R1
N
R1
N
H
O
O
N
O
O
N
6
6
2N
1
1
2N
O
HO
N
3
5
3
5
4
4
R2
H3CC
O
R2
1
2
3-6
7-10
3 R1 = C6H5; R2 = CH3
4 R1 = CH3; R2 = C6H5
5 R1 = R2 = C6H5
7 R1 = C6H5; R2 = CH3
8 R1 = CH3; R2 = C6H5
9 R1 = R2 = C6H5
6 R1 = R2 = CH3
10 R1 = R2 = CH3
R1
R3
O
O
N
N
R2
11-28
11 R1 = C6H5; R2 = CH3; R3 = CO2C2H5
12 R1 = CH3; R2 = C6H5; R3 = CO2C2H5
13 R1 = C6H5; R2 = R3 = CH3
14 R1 = R3 = CH3; R2 = C6H5
15 R1 = R3 = C6H5; R2 = CH3
16 R1 = CH3; R2 = R3 = C6H5
17 R1 = R2 = C6H5; R3 = 2-furyl
18 R1 = C6H5; R2 = CH3; R3-2-furyl
19 R1 = CH3; R2 = C6H5; R3 = 2-furyl
20 R1 = R2 = C6H5; R3 = 3-pyridyl
21 R1 = C6H5; R2 = CH3; R3 = 3-pyridyl
22 R1 = CH3; R2 = C6H5; R3 = 3-pyridyl
23 R1 = C6H5; R2 = CH3; R3 = CO2H
24 R1 = CH3; R2 = C6H5; R3 = CO2H
25 R1 = R2 = CH3; R3 = CO2H
26 R1 = C6H5; R2 = CH3; R3 = CONH2
27 R1 = C6H5; R2 = CH3; R3 = CN
28 R1 = C6H5; R2 = CH3; R3 = 5-tetrazolyl

194
M. A. Khan, G. P. Ellis and M. C. Pagotto
Vol. 38
Table 1
Data for 1H-pyrano[2,3-c]pyrazol-4-ones
1
Compound
No.
Yield
(%)
mp °C
(from aqueous
ethanol)
Molecular
Formula
IR
(cm )
H-nmr δ/ppm (J in Hz)
-1
(solvent)
11
12
13
14
74
86
20
10
127-128
184-185
152-153
187-188
C
C
C
C
H
N O
1738 (C=O ester)
1.40 (3H, t, J = 8, O-CH -CH );
2 3
16 14
2
4
4
2
2
1655 (C=O Pyrone)
1135 (C-O-C-Pyrone)
870 (C-H Pyrone)
2.60 (3H, t, CH ); 4.40
3
(2H, q, O-CH -CH , J = 8), 7.00
2
3
(1H, s, H-5); 7.62 (5H, m,Phenyl-H)
(deuteriochloroform)
H
N O
1735 (C=O ester)
1.42 (3H, t, J = 8, O-CH -CH );
16 14
2
2 3
1658 (C=O Pyrone)
1135 (C-O-C Pyrone)
875 (C-H Pyrone)
4.42 (2H, q, J = 8, O-CH -CH );
2 3
3.95 (3H, s, CH ); 7.00 (1H, s, H-5)
3
7.40-8.28 (5H, m, Phenyl-H)
(deuteriochloroform)
H
N O
1660 (C=O Pyrone)
1168 (C-O-C Pyrone)
930 (C-H Pyrone)
2.38 (3H, s, CH -6);
14 12
2
3
2.60(3H, s, CH -3);
3
5.98 (1H, s, H-5);
7.47 (5H, m, ph-H)
(deuteriochloroform)
H
N O
1665 (C=O Pyrone)
1170 (C-O-C Pyrone)
840 (C-H Pyrone)
2.35 (3H, s, CH -3);
14 12
2
3
3.85 (3H, s, N-CH );
3
6.02 (1H, s, H-5);
7.40-8.30 (5H, m, Phenyl H)
(deuteriodimethyl sulfoxide)
15
16
17
50
15
37
210-211
181-182
219-220
C
C
C
H
N O
1665 (C=O Pyrone)
1105 (C-O-C Pyrone)
850 (C-H Pyrone)
2.63 (3H, s, CH );
6.64 (1H, s, H-5);
7.62 (10H, m, Phenyl H)
(deuteriochloroform)
19 14
2
2
2
3
3
H
N O
1640 (C=O Pyrone)
1135 (C-O-C Pyrone)
840 (C-H Pyrone)
4.00 (3H, s, CH );
19 14
2
3
6.65 (1H, s, H-5);
7.60-8.30 (10H, m, Phenyl H)
(deuteriochloroform)
6.50 (1H, m, furan H-4);
6.54 (1H, s, H-5);
6.90 (1H, d, J = 7, furan H-3)
7.60-8.40 (11H, m, Phenyl H and
furan H-5)
H
N O
1648 (C=O Pyrone)
1130 (C-O-C Pyrone)
850 (C-H Pyrone)
22 14
2
(deuteriochloroform)
18
19
27
37
201-202
202-203
C
C
H
N O
1660 (C=O Pyrone)
1095 (C-O-C Pyrone)
850 (C-H Pyrone)
2.65 (3H, s, CH );
6.58 (1H, s, H-4);
6.60 (1H, s, H-5);
7.00 (1H, d, J = 7, H-3 );
7.66 (6H, m, Phenyl H and H-5)
(deuteriochloroform)
17 14
2
3
3
3
H
N O
1655 (C=O Pyrone)
1125 (C-O-C Pyrone)
850 (C-H Pyrone)
3.90 (3H, s, CH );
17 14
2
3
6.42 (1H, s, H-5);
6.73 (1H, m, H-4);
7.94 (1H, d, J = 7, H-3);
7.66 (6H, m). (Phenyl-H and H-5)
(deuteriodimethyl sulfoxide)
7.55-8.12 (11H, m, Phenyl H and H-5)
9.02 (4H, m, pyridine-H).
(deuteriochloroform-trifluoro
acetic acid)
20
21
37
32
255-256
207-208
C
C
H
N O
1648 (C=O Pyrone)
1140 (C-O-C Pyrone)
880 (C-H Pyrone)
23 15
3
2
H
N O
1660 (C=O Pyrone)
1110 (C-O-C Pyrone)
895 (C-H Pyrone)
2.52 (3H, s, CH );
18 13
3
2
3
6.98 (1H, s, H-5);
7.70 (5H, m, C H );
6
5
8.10-9.15(4H, m, pyridine-H)
(deuteriodimethyl sulfoxide)
22
50
224-225
C
H
N O
1630 (C=O Pyrone)
1140 (C-O-C Pyrone)
880 (C-H Pyrone)
3.95 (3H, s, CH );
6.62 (1H, s, H-5);
18 13
3
2
3
7.30 (5H, m, C H );
6
5
8.10-9.10(4H, m, pyridine-H)
(deuteriochloroform)

Jan-Feb 2001
Pyranopyrazoles III Synthesis of 1H-Pyrano[2,3-c] pyrazol-4-ones
195
Table 1 (continued)
1
Compound
No.
Yield
(%)
mp °C
(from)
Molecular
Formula
IR
(cm )
H-nmr δ/ppm (J in Hz)
-1
(solvent)
(aqueous ethanol)
23
24
25
26
74
69
35
79
277-278
C
C
H
N O
3000-2500 (br-OH)
1720 (C=O acid)
2.50 (3H, s, CH );
6.82 (1H, s, H-5);
14 10
2
4
3
1630 (C=O Pyrone)
1128 (C-O-C Pyrone)
860 (C-H Pyrone)
3000-2500 (br-OH)
1740 (C=O acid)
1635 (C=O Pyrone)
1150 (C-O-C Pyrone)
890 (C-H Pyrone)
3150-2500 (br-OH)
1705 (C=O acid)
7.65 (5H, m, C H );
6 5
(deuteriochloroform-deuterio
dimethyl sulfoxide)
> 300
H
N O
4.18 (3H, s, CH );
14 10
2
4
3
7.50-7.87 (6H, m, Phenyl H and H-5)
(deuteriodimethyl sulfoxide-
trifluoro acetic acid
218-220
272-273
C H N O
2.40 (3H, s, CH -3);
3
3.35 (3H, s, N-CH );
7.40 (1H, s, H-5).
(deuteriodimethyl sulfoxide)
9
8
2
4
3
1630 (C=O Pyrone)
1115 (C-O-C Pyrone)
895 (C-H Pyrone)
3400 (NH)
C
H
N O
2.52 (3H, s, CH );
3
14 11
3
3
1695 (C=O amide)
1660 (C=O Pyrone)
1115 (C-O-C Pyrone)
895 (C-H Pyrone)
2230 (C≡N)[a]
1665 (C=O Pyrone)
1145 (C-O-C Pyrone)
850 (C-H Pyrone)
3070 (NH)
7.80 (5H, m, C H );
6.85 (1H, s, H-5)
(deuteriodimethyl sulfoxide)
6
5
27
28
91
87
150-151
267-268
C
H N O
2.61 (3H, s, CH );
14
9
3
2
3
6.78 (1H, s, H-5);
7.60 (5H, m, C H ).
6
5
(deuteriochloroform)
2.58 (3H, s, );
C
H N O
14 10 6 2
1655 (C=O Pyrone)
1125 (C-O-C Pyrone)
895 (C-H Pyrone)
7.05 (1H, s, H-5);
7.62 (5H, m, C H ).
6
5
Deutrio dimethyl sulfoxide -
deuteriochloroform
[a] – in nujol
provides an intermediate ''β-diketone'' which
in an acid solution to the respective
for other esters)
was cyclized
Table 2
Elemental Analyses for 1H-pyrano[2,3-c]pyrazol-4-ones
1H-pyrano[2-3-c]
pyrazol-4-ones (11-22) [9], (Scheme). An
Molecular
Formula
Compound Calculated (%)
Found (%)
H N
intermediate-β-diketone from the reaction of 10 with diethyl
oxalate on cyclization gave a mixture of the expected ester
and the corresponding acid (25). This mixture, as well as the
esters 11 and 12, on acid hydrolysis afforded the
''corresponding'' acids 23-25.
An ammonolysis [10] of ester 11 afforded the amide (26)
in 79% yield. The amide (26) on dehydration with
p-toluenesulfonyl chloride in pyridine [10] afforded the
nitrile (27) which in turn, on reaction with sodium azide in
N,N-dimethylformamide [11] gave 3-methyl-1-phenyl-6-
(tetrazol-5-yl)-1H-pyrano[2,3-c]pyrazol-4-one (28) in
87% yield.
No.
C
H
N
C
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
C
C
C
C
C
C
C
C
C
C
C
C
C
C
H
N O
64.42 4.73
64.42 4.73
9.39
9.39
64.31 4.80 9.45
64.38 4.93 9.28
70.08 4.94 11.66
70.10 5.11 11.38
75.13 4.77 9.33
75.37 4.67 9.05
74.31 3.86 7.64
69.73 4.03 9.41
69.95 4.01 9.35
75.31 4.28 11.27
71.02 4.30 13.68
70.98 4.30 13.53
61.92 3.74 10.27
61.83 3.76 10.34
51.71 3.65 13.37
62.05 4.15 15.90
66.88 3.81 16.48
57.08 3.58 28.81
16 14
2
4
4
2
2
2
2
3
3
3
2
2
2
4
4
H
N O
16 14
2
H
N O
69.99 5.03 11.66
69.99 5.03 11.66
14 12
2
H
N O
14 12
2
H
N O
75.48 4.67
75.48 4.67
74.57 3.98
69.86 4.14
69.86 4.14
9.27
9.27
7.91
9.58
9.58
19 14
2
H
N O
19 14
2
H
N O
2
22 14
H
N O
17 14
2
H
N O
2
17 14
H
N O
75.60 4.14 11.50
71.26 4.32 13.85
71.26 4.32 13.85
62.22 3.73 10.37
62.22 3.73 10.37
51.93 3.87 13.47
62.42 4.12 15.61
66.93 3.61 16.73
57.14 3.43 28.56
23 15
3
H
N O
All the 1H-pyrano[2,3-c]pyrazol-4-ones (11-28)
obtained during the present work are presented in Table
1 and were characterized by elemental analyses,
18 13
3
H
N O
18 13
3
H
N O
14 10
2
H
N O
2
14 10
1
infrared and H-nmr spectra (Tables 1 and 2). The
C H N O
9
8 2 4
infrared spectra of new compounds 11-28 displayed the
C
H N O
14 11 3
3
2
characteristic absorption band for the pyrone ring
C
H N O
14
9
3
2
-1
carbonyl in the region 1665-1630 cm , the C-O-C
C
H N O
14 10 6

196
M. A. Khan, G. P. Ellis and M. C. Pagotto
Method.
Vol. 38
Scheme
R1
N
R1
N
A mixture of 0.4 moles of the pyrazolone, 100 g of
anhydrous sodium acetate and 120 ml of acetic anhydride was
stirrer and heated under reflux for an hour. The cooled
reaction mixture was poured onto 700 g of crushed ice and
extracted with chloroform (3x200 ml). The chloroform extract
was washed with cold 5% sodium hydroxite (3x500 ml). The
aqeous extracts were combined and acidified with 5% hydro-
cloric acid, the 4-acetyl-5-hydroxypyrazole (7-10) was
filtered and purified.
O
HO
O
NaOC2H5 or NaH
N
N
(CH3CO)2O
and R3CO2C2H5, ∆
CH3CO2Na, ∆
R2
R2
3-6
CH3
7-10
R1
R1
HO
R3
R3
N
N
N
O
O
4-Acetyl-5-hydroxyl-3-methyl-1-phenylpyrazole (7).
N
H+, ∆
-H2O
-1
Compound 7 had mp 60-61° (lit [8] mp 62-63°); ir (cm ):
O
R2
R2
1
3100 (br.OH), 1630 (C=O); H-nmr (carbon tetrachloride): δ
O
2.30 (6H, s, CH ), 7.00-7.85 (5H, m, C H ), 12.85 (1H, br. OH).
3
6 5
11-22
intermediate
4-Acetyl-5-hydroxy-l-methyl-3-phenylpyrazole (8).
Compound 8 has mp 89-90° recrystallized from aqueous
-1
ethanol); yield 35%, ir (cm ): 3150-3100 (br. OH), 1615 (C=O);
-1
stretching mode in the region 1170-1100 cm and the
typical deformation of an isolated C-H in the 890-820
1
H-nmr (deuteriochloroform): δ 2.10 (3H, s, COCH ), 3.70
(3H, s, N-CH ), 7.35 (5H, s, C H ), 10.30 (br. OH).
3
-1
3
6 5
cm region, that have previously been observed for
Anal. Calcd. For C
H N O : C,66.65; H, 5.59; N, 12.96.
12 12 2 2
various derivatives of chromones [12,13]. For
compound 27 the characteristic nitrile absorption was
not observed when acquired as a potassium bromide
disk, however, was observed as a weak absorption at
2230 cm when acquired in nujol mull. This
phenomenon was also observed earlier [14] and was
ascribed to the absence of a contribution of the dipolar
form (-C =N ) of the cyano group when attached to an
electron deficient carbon at position 6 of the molecule.
The H-nmr spectra were consistent with the structure
Found: C, 66.95; H. 5.60: N, 12.77.
4-Acetyl-5-hydroxy-1,3-diphenylpyrazole (9).
Compound 9 has mp 141-142° (aqueous. ethanol); yield 23%,
ir (cm ): 3100 (br.OH), 1620 (C=O); H-nmr (carbon tetra-
chloride-deuteriochloroform); δ 2.15 (3H, s, COCH ), 7.00-8.00
-1
-1
1
3
(10H, m, C H ), 11.95 (br.OH).
6
5
+
-
Anal. Calcd. For. C H N O : C 73.37, H, 5.07; N, 10.07.
17 14 2 4
Found: C, 73.44. H, 5.21; N, 9.95.
1
4-Acetyl-5-hydroxy-1,3-dimethylpyrazole (10).
of these new compounds. All new compounds with the
exception of 20 and 24 displayed a singlet for the
proton at position-5 between δ 6.00 and 7.50 and the
remaining signals correspond to the other protons
contained in the various substituents. The H-5 for 20
and 24 is located within the envelop of the signals for
the benzene and pyridine substituents respectively, and
this shift is ascribed to the solvent effect of
trifluoroacetic acid.
Compound 10 has mp 125-126° (Sublimation); yield 45%, ir
-1
1
(cm ): 3270 (br. OH), 1640 (C=O); H-nmr (deuterio-
chloroform): δ 2.32 (6H,s, COCH and pyrazole CH ), 3.54
3
3
(3H, s, N-CH ), 7.05 (br.OH).
3
Anal. Calcd. For C H N O : C, 54.53, H, 6.54; N, 18.17.
7
10 2 2
Found: C, 54.82; H, 6.35; N, 18.40.
1H-Pyrano [2,3-c]pyrazol-4-ones (11-22).
Method A.
A mixture of 1.38 g of sodium in 40 ml of ethanol was heated
under reflux untill sodium was dissolved. Then 0.03 mole of a
4-acetyl-5-hydroxypyrazole was added with stirring and
heating under reflux for 0.5 hour followed by addition of
30 mmoles of diethyl oxalate. The mixture was heated under
reflux for another 2 hours, cooled and 3ml of concentrated
sulfuric acid was cautiously added. After heating at 60-70° on a
water bath for 0.5 hour, the reaction mixture was cooled and
200g of crushed ice was added to precipitate the β-diketone
intermediate, which was filtered, dried and submitted to
cyclization in 50 ml of dry ethanol containing 0.5 ml of
concentrated sulfuric acid. After 1 hour of heating under reflux,
the reaction mixture was poured onto crushed ice, the
precipitate filtered and dried to give the desired esters 11 and 12
(Table 1 and 2). In the reaction of 10, a mixture consisting of
the ester and the hydrolyzed acid (25) was obtained, which was
further hydrolyzed to give the acid (see below).
EXPERIMENTAL
1
The H-nmr spectra were obtained on a Hitachi Perkin-
Elmer model R-20B spectrometer operating at 60 MHz
(tetramethylsilane as internal standard). The infrared
absorption spectra were acquired on a Perkin-Elmer model
727 spectrophotometer as potassium bromide disks. Melting
points were determined with a Fisher-Johns apparatus and are
uncorrected. Elemental analyses were determined on a Perkin-
Elmer model 240.
4-Acetyl-5-Hydroxypyrazoles.
The following 4-acetyl-5-hydroxypyrazoles were prepared
according to the method of Graham [8] from the reaction of the
appropriate pyrazol-5-ones [15] with a mixture of acetic
anhydride and anhydrous sodium acetate.

Jan-Feb 2001
Method B.
Pyranopyrazoles III Synthesis of 1H-Pyrano[2,3-c] pyrazol-4-ones
197
3-Methyl-1-phenyl-6-(tetrazol-5-yl)-1 H-pyrano[2,3-c]pyrazol-
4-one (28).
A mixture of 5 mmoles of of acetylhydroxypyrazole and
20 mmoles of sodium hydride in 30 ml of dioxane was heated on
a water bath for 0.4 hour followed by addition of 7 mmoles of an
appropriate ester (ethyl acetate, ethyl benzoate, ethyl 2-furoate or
ethyl nicotinate). The resulting mixture was heated under reflux
for a further 4 hour period and on cooling the sodium salt of the
β-diketone was precipitated by addition of ether. After 0.4 hour
the precipitate was filtered off and triturated with 5%
hydrochloric acid. The free β-diketone was extracted with
chloroform (3x100ml), the solvent was removed and the residue
was taken up in a mixture of 20 ml of sulfuric acid-acetic acid
(1:10). After heating on a water bath for 2 hour the reaction
mixture was poured onto crushed ice (200 g) and the precipitated
product (13-19) was filtered off and recrystallized from a suitable
solvent (Tables 1 and 2).In the case of reactions with ethyl
nicotinate, the expected products (20-22) (Tables 1and 2) did not
immediately precipitate on addition to ice and were isolated by
extraction with chloroform (3x50ml), the solvent was removed
and the residues were recrystallized from aqueous ethanol.
A mixture of 0.6 g (2 mmole) of 27, 0.15 g of sodium azide and
0.14 g of ammonium chloride in 8 ml of N,N-dimethylformamide
was heated at 120-130 °C (equipped with calcium chloride tube)
for 10 hours and left overnight. The reaction mixture was poured
onto 30 g of crushed ice, acidified with 5% hydrochloric acid and
the yellowish precipitate was filtered off. The product was
recrystallized from a mixture of benzene and ethyl acetate to give
0.61 g of 28 (Tables 1 and 2).
Acknowledgements.
Continuous support from Conselho Nacional de
Desenvolvimento Cientifico e Tecnologico (CNPq) is gratefully
acknowledged. Mario Celso Pagotto also thanks Coordenacao de
Aperfeicoamento Pessoal de Nivel Superior (CAPES) for the
fellowship.
REFERENCES AND NOTES
4-Oxo-1H-Pyrano[2,3-c]pyrazole-6-carboxylic Acids (23-25).
[1] M. A. Khan and A. G. Cosenza, J Heterocyclic Chem., 19,
1077 (1982) and references therein.
General Method.
[2a] G. Heinisch, C. Hollub and W. Holzer, J. Heterocyclic. Chem.,
28, 1047 (1991); [b] S. Gelin, B. Chantegrel and A. I. Nadi, J Org. Chem.,
48, 4078 (1983).
[3] M. A. Khan, M. C. Pagotto and G. P. Ellis, Heterocycles, 6,
983 (1977).
[4] A. O. Fitton and R. K. Smalley, Practical Heterocyclic
Chemistry, Academic Press, London, 1968 p 24.
[5] S. Veibel, K. Eggersen and S. C. Linholt, Acta Chem. Scand.,
8, 768 (1954).
A mixture of 1 g of the ester (11, 12 or the reaction mixture of
10 with diethyl oxalate) and a mixture 20 ml of concentrated
hydrochloric acid and glacial acetic acid (1:1) was heated on a
water bath for 1 hour. The resulting mixture was poured onto
100 g of crushed ice and the precipitate was filtered, dried and
recrystallized to yield the acids 23-25 (Tables 1 and 2).
3-Methyl-4-oxo-1-phenyl-1H-pyrano[2,3,-c]Pyrazole-6-carbox-
amide (26).
[6] A. Michaelis, Ann., 352, 152 (1907).
[7] N. V. Khromov-Borisov, Zh. Obshch. Khim., 25, 136 (1955).
[8] B. Graham, US Pat. 2694703 (1954); Chem. Abstr., 49, 3706
(1955).
[9] G. P. Ellis and G. Barker, Progr. Med. Chem., 9, 65 (1972).
[10] G. P. Ellis and D. Shaw, J. Med Chem., 15, 865 (1972).
[11] W. G. Finnegan, R. A. Henry and R. Lofquist, J. Am. Chem.
Soc., 80, 3908 (1958).
Ammonia was bubbled for 0.5 hour through a solution of 0.7 g
(2.3 mmoles) of the ester 11 in 100 ml of dry ethanol at 0-5 °C.
The precipitate was filtered, dried and recrystallized from ethanol
to give 0.5 g of 26 (Tables 1 and 2).
3-Methyl-4-oxo-l-phenyl-1H-pyrano [2,3,-c] pyrazole-6-carbo-
nitrile (27).
[12] N. B. Colthup, L. H. Daly and S. E. Wiberley, Introduction to
Infrared and Raman Spectroscopy, Academic Press, New York, (1964).
[13] J. H. Looker and W. W. Hanneman, J. Org. Chem., 27, 381
(1962).
[14] G. P. Ellis and D. Shaw, J. Chem. Soc., Perkin Trans. I, 779
(1972).
A mixture of 0.5 g (2 mmole) of 26, 0.6 g of p-toluenesulfonyl
chloride, 1 ml of pyridine and 10 ml of N, N-dimethylformamide
was heated on an oil bath at 80-90 °C for 8 hours, allowed to
stand overnight and then poured onto 20 g of crushed ice. The
precipitate was filtered, dried and recrystallized from aqueous
ethanol to give 0.42 g of 27 (Tables 1 and 2).
[15] L. Knorr, Ber., 16, 2597 (1883).