Benzopyrans. Part 42 [1]. Reactions of 4-oxo-4H-1-benzopyran-3-carbaldehyde with some active methylene compounds in the presence of ammonia

Article abstract of DOI:10.1002/jhet.5570380632

The title aldehyde 1 in the presence of ammonia gives the pyridine derivatives 9-11 respectively with acetylacetone, diethyl malonate and ethyl cyanoacetate, and ethyl (or methyl)-1-benzopyrano[4,3-b]pyridine-3-carboxylate 22 (or 23) with ethyl (or methyl

Full text of DOI:10.1002/jhet.5570380632

Nov-Dec 2001
Benzopyrans. Part 42 [1]. Reactions of 4-Oxo-4H-1-benzopyran-
3-carbaldehyde with Some Active Methylene
1459
Compounds in the Presence of Ammonia
Chandra Kanta Ghosh*[a], Anirban Ray[a] and Amarendra Patra[b]
[a] Organic Chemistry Laboratory, Department of Biochemistry, Calcutta University, Calcutta-700019, India
[b] Department of Pure Chemistry, Calcutta University, Calcutta-700009, India
Received January 24, 2001
The title aldehyde 1 in the presence of ammonia gives the pyridine derivatives 9-11 respectively with
acetylacetone, diethyl malonate and ethyl cyanoacetate, and ethyl (or methyl)-1-benzopyrano[4,3-b]pyri-
dine-3-carboxylate 22 (or 23) with ethyl (or methyl) acetoacetate. Acetylacetone pretreated with ammonia
condenses with 1 giving the fused pyridine 24. Ammonia converts the ester 6 to the pyridine 13 or 14.
Chromic acid oxidation of 22 and 23 affords the coumarinopyridines 25 and 26, respectively.
J. Heterocyclic Chem., 38, 1459 (2001).
The title aldehyde 1 condenses readily in the presence of
path a is formed. These two conflicting reports [3,4]
prompted us to record herein our findings on the condensa-
tion of the title aldehyde 1 with acetylacetone, diethyl mal-
onate, ethyl cyanoacetate and ethyl as well as methyl ace-
toacetate in the presence of liquor ammonia.
The aldehyde 1a when refluxed with excess acetylace-
tone in a mixture of ethanol and liquor ammonia afforded
the pyridine 9a. Thus in the presence of either ammonia or
ammonium acetate as the source of ammonia, the reaction
between 1 and acetylacetone follows the same course as
depicted in Scheme 1 – path a. Under similar conditions 1
gave 10 with diethyl malonate and 11 (Tables 1 and 2) in
complete exclusion of 12 with ethyl cyanoacetate via the
intermediates 4 and 5, respectively. It is relevant to men-
tion here that 3-cyanopyridone 11 and the corresponding
amide also result from the pyridine mediated condensation
of 1 with cyanoacetamide [5]. In contrast, ethyl acetoac-
a base with active methylene compounds [2]. When a mix-
ture of 1, acetylacetone (2, X = Y = Ac) and ammonium
acetate is refluxed in ethanol, the initial condensate 3
undergoes nucleophilic attack by ammonia at its pyran
2-position with concomitant opening of the pyran ring, the
resultant intermediate 8 (X = Y = Ac) cyclising to the pyri-
dine 9 (Scheme 1 – path a) [3]. When refluxed with methyl
acetoacetate and liquor ammonia in methanol, the alde-
hyde function of 1 is involved in the Hantzsch pyridine
synthesis so as to form the 1,4-dihydropyridine 16 evi-
1
dently via the Michael adduct 15 (R = Me) of the initial
condensate 7 and methyl acetoacetate (Scheme 1 – path b)
[4]; neither the pyridine 13 (CO Me in place of CO Et)
2
2
nor 14 anticipated to arise by the mechanism as depicted in
etate (2, X = Ac, Y = CO Et) with 1 under reflux in ethanol
2
containing liquor ammonia gave neither the pyridine 13
(or 14) (Scheme 1 – path a) nor the dihydropyridine 17
(path b); the benzopyranopyridine 22 (Tables 3 and 4),
identical with that derived from 1 and ethyl β-aminocroto-
nate (18), was the sole product. Formation of 5-hydroxy-
5H-1-benzopyrano[4,3-b]pyridines analogous to 22-24 by
treating 1 with various acyclic [6,7] as well as carbocyclic
[7] enamines is well known.
Under the present experimental conditions ammonia can
only generate from diethyl malonate and ethyl cyanoac-
etate the corresponding carbanions which condense with
the aldehyde 1 and the resultant condensates 4 and 5 on
further reaction with ammonia give the pyridines 10 and
11, respectively (Scheme 1 – path a). Under similar condi-
tions ammonia can generate the corresponding carbanions
from acetylacetone and ethyl as well as methyl acetoac-
etate or add to their ketone functionality to form respec-
tively the enamines 20, 18 and 19 (Scheme 2). The methyl-
ene group of acetylacetone being highly active, the gener-
ation of the corresponding carbanion by ammonia predom-
inates over the formation of the enamine 20; hence treat-
ment of 1 with acetylacetone in the presence of ammonia

1460
C. K. Ghosh, A. Ray and A. Patra
Vol. 38
Table 1
3-Ethoxycarbonyl-, 3-Cyano- and 3-Acetyl-5-(2-hydroxybenzoyl)pyridin-2-one (10, 11 and 14)
and Ethyl 2-Methyl-5-(2-hydroxybenzoyl)pyridine-3-carboxylate 13
1
Comp. No
Yield
Mp
Found
H nmr data : δ ppm [a]
(Mol. formula) (%)
(°C)
(Calculated)
C
H
N
NH
OH
6- or 4- or 4´-H 6´-H 5´- and/or OCH Me 2-Me CH Me
2
2
(br s) (br s) 4-H 6-H
(d) [b] (d) [b]
3´-H
(q)
(5´-Me)
(s)
(t)
___
10a
(C
66
154
140
178
>240
>240
>240
91
62.4
4.2
4.7
4.9)
4.9
4.6)
4.5
12.58 10.22 8.36 7.90 7.36 7.29
6.91
6.82
6.93
4.19
4.18
1.17
1.21
H
NO )
(62.7 4.6
64.1 4.8
(63.8 5.0
56.2 3.5
15 13
5
(2.18)
___
10b
(C
72
85
67
76
74
60
72
12.53 9.98
8.34 7.91 7.16 7.06
H
NO )
16 15
5
10c
(C
11.59 10.43 8.32 7.93 7.37 7.28
4.19
1.21
H
NClO )
(56.0 3.8
___
4.4)
___
15 12
5
___
___
___
___
6.88
11a [c,d]
(C H N O )
[e]
[e]
10.31 8.36 8.02 7.36
13
8 2 3
___
___
___
___
(2.18)
11b
(C
65.8
4.4
11.3
11.0)
10.4 [e]
10.2)
5.0
4.7)
4.6
4.4)
5.8
10.57 8.37 8.06 7.40 7.29
10.04 8.32 8.01 7.17 7.10
11.56 8.83 8.46 7.29 7.25
6.94
6.82
6.94
7.03
6.97
H
N O )
(66.1 4.0
56.5 2.9
(56.8 2.6
68.0 5.4
(68.2 5.7
59.8 4.0
(60.1 4.4
65.2 4.4
(65.4 4.3
14 10
2 3
___
11c [c]
(C H N ClO )
13
7
2
3
___
2.89
(2.21)
2.89
13b
(C
4.37
1.37
H
NO )
17 17
4
___
7.46
13c
(C
98
11.64 8.86 8.48
4.40
1.39
H
NClO )
16 14
4
___
___
___
14a [f]
(C
12.72 10.22 8.32 8.01 7.41 7.33
H
NO )
63
180
5.5)
14 11
4
[a] Spectra of 10, 11 and 14 were recorded in DMSO-d solution and those of 13 in CDCl solution; aromatic protons show normal splitting pattern. [b] J
4,6
6
3
varies from 2.1 to 2.7 Hz. [c] Ir (potassium bromide) for 11a : 3130 (NH), 3050 (OH), 2200 (CN), 1675 (amide CO); 11c : 3170 (NH), 3070 (OH), 2230
-1
(CN), 1675 (amide CO), 1630 (ketone CO) cm . [d] Lit. [5] mp 266-268 °C (dec.). [e] Not detected. [f] Acetyl protons appear as a singlet at δ 2.56 ppm.
follows the reaction course as depicted in Scheme 1 – path a
to give the pyridine 9. In contrast, with ammonia ethyl ace-
toacetate having a comparatively less active methylene
group forms the enamine 18 in preference to the correspond-
ing carbanion. The resultant enamine 18 undergoes Michael
addition to the α,β-unsaturated carbonyl functionality of 1
with concomitant opening of the pyran ring [6] and subse-
1
quent recyclisation to give the intermediate 21 (R = OEt),
the latter ultimately cyclising to 22 (Scheme 2). If ammonia
had generated the carbanion from ethyl acetoacetate, 1
would have been converted via 6 into the pyridine 13 or 14
(Scheme 1 – path a), the latter being indeed obtained by
treating the preformed condensate 6 [8,9] with ammonia.
Haas et al. [7] reported the formation of 13a (m.p. 66-67°)
by refluxing 6a with liquor ammonia in ethanol. The same
procedure gave in our hand 13b and 13c respectively from
6b and 6c but 14a from 6a (Tables 1 and 2).
On subjecting methyl acetoacetate to condensation with
1 in refluxing methanol - liquor ammonia we obtained
only 23 (Tables 3 and 4) in contrast to the previously
reported [4] exclusive formation of 16. The fused pyridine
23 arises through condensation of 1 with the enamine 19,
derived in situ from methyl acetoacetate and ammonia
(Scheme 2). Thus methyl acetoacetate behaves similarly as
ethyl acetoacetate towards the aldehyde 1 in the presence
of ammonia. In the absence of experimental details [4], it
is difficult to pinpoint the reaction conditions under which
1 with methyl acetoacetate and ammonia gives 16 instead
of 23. The formation of the tricyclic system (22 and 23) is
independent on the quantity of liquor ammonia used. The
presence of hemiacetal functionality in 22 and 23 was con-
firmed by chromic acid oxidation of these compounds in
acetic acid to the coumarinopyridines 25 and 26 (Tables 3
and 4), respectively.

Nov-Dec 2001
Benzopyrans. Part 42[1]. Reactions of 4-Oxo-4H-1-benzopyran-3-carbaldehyde
1461
Table 2
13
C Nmr Data of the Pyridines 10, 11, 13 and 14 [a]
Carbon No./
10a
10b
10c
11a
11b
11c
13b
13c
14a
Type
2
3
4
5
6
1´
2´
3´
159.1
119.8
146.3
116.0
143.6
125.2
155.6
116.8
133.1
119.6
130.1
159.1
119.8
146.1
116.0
143.6
124.0
153.6
116.7
133.7
128.3
130.0
159.1
119.9
146.5
115.9
143.2
123.2
154.2
118.6
132.3
126.9
129.1
159.0
103.8
148.0
115.7
146.6
124.3
155.9
116.8
133.4
119.6
130.3
159.8
103.3
148.1
115.6
146.6
123.9
153.7
116.7
134.0
128.3
130.2
159.9
103.5
147.9
115.6
147.0
123.2
154.3
118.7
132.6
126.3
129.2
161.2
128.2
138.7
118.6
151.1
125.6
162.9
118.4
137.9
131.2
132.3
198.0
24.7
161.7
124.0
138.7
119.6
151.1
125.8
163.6
120.4
136.8
130.5
131.6
197.3
24.9
160.9
124.8
146.1
116.4
142.4
125.8
155.5
116.5
132.9
119.4
129.8
4´
5´
6´
Salicyloyl CO
2-Me
191.1
___
191.2
___
189.4
___
190.3
___
190.3
___
188.7
___
191.2
___
3-COR/CN
164.2
60.9
14.4
___
164.1
60.8
14.3
20.0
164.1
60.9
14.3
___
[b]
116.6
116.6
165.5
61.6
14.1
165.4
61.7
14.1
___
196.2
___
___
___
___
OCH Me
2
___
___
___
___
___
OCH Me/COMe
30.5
___
2
5´-Me
19.9
20.3
[a] Spectra are recorded in the same solution as stated in the footnote [a] of Table 1. [b] Not detected
Table 3
1-Benzopyrano[4,3-b]pyridines 22-26
1
Comp. No.
(Mol. formula)
Yield
(%)
M.p
(ºC)
(M.p[6])
Found
(Calculated)
H
H nmr data : δ ppm [a]
4-H
(s)
10-H
OH
(d) [b]
8-H 9- and/or 5-H
OCH Me
2-Me
CH Me
2
2
C
N
7-H
(d) [b]
(q)
(CO Me or
(t)
2
COMe) (s)
22a [c]
52
48
57
43
46
47
22
25
18
53
47
61
42
65
190
210
220
67.1
(67.4
68.2
(68.2
60.4
(60.1
66.7
(66.4
67.1
(67.4
60.2
(58.9
70.9
(70.6
71.7
(71.4
62.0
(62.2
67.4
(67.8
68.4
(68.7
60.1
(60.5
67.3
(66.9
59.7
(59.3
5.0
5.3 4.9)
5.3 4.8
5.7 4.6)
4.1 4.6
4.4 4.4)
4.5 5.4
4.8 5.2)
5.0 5.2
5.2 4.9)
4.2 4.2
4.0 4.6)
4.8 5.7
5.1 5.5)
5.2 5.0
5.6 5.2)
4.5 5.1
4.2 4.8)
4.3 5.1
4.6 5.0)
5.0 4.3
5.1 4.7)
3.4 4.2
3.8 4.4)
3.7 5.4
4.1 5.2)
3.5 4.9
3.3 4.6)
5.2
8.19
8.13
8.23
8.20
8.12
8.13
8.22
7.95
8.22
9.02
9.03
9.08
9.10
8.97
8.21
8.01
8.18
8.25
7.99
8.09
8.20
8.10
8.12
8.55
8.34
8.59
8.63
8.42
7.67
7.58
7.79
7.69
7.61
7.78
7.40
4.75
7.41
7.23
7.49
7.47
7.20
7.41
7.08
6.93
7.14
7.13
6.93
7.06
6.49
6.45
6.58
6.53
6.42
6.48
6.48
6.47
4.28
4.29
2.76
1.29
1.30
(C
H NO )
16 15 4
22b [d]
(C
2.77
H
NO )
4
17 17
22c
(C
4.34
2.80
1.35
H
NClO )
4
16 14
___
___
23a
(C
210
(237)
182
2.81
(3.87)
2.75
(3.81)
2.74
(3.82)
2.68
(2.57)
2.83
(2.61)
2.67
(2.56)
2.99
H
NO )
4
15 13
___
___
___
___
___
___
___
___
___
___
23b [d]
(C
H
NO )
16 15
4
23c
(C
214
(202)
170
H
NClO )
15 12
4
24a
(C
7.14-7.03
H
NO )
15 13
3
24b [d]
(C
175
7.22
7.41
7.59
7.38
7.56
7.63
7.49
6.98
7.08
7.36
7.23
7.34
7.41
7.24
H
NO )
16 15
3
24c [c]
(C
222
(202)
168
7.76
6.48
H
NClO )
15 12
3
___
___
25a [c]
(C
4.43
4.43
1.44
1.43
H
NO )
4
16 13
___
___
___
___
___
___
___
___
25b [d]
(C
192
168
210
197
3.00
3.04
H
NO )
4
17 15
25c
(C
4.45
1.45
H
NClO )
4
16 12
___
___
26a
(C
3.04
(3.97)
3.02
H
NO )
4
15 11
___
___
26c
(C
H
NClO )
(3.96)
15 10
4
[a] Spectra of 24b, 25 and 26 were recorded in CDCl and those of others in DMSO-d ; aromatic protons show normal splitting. [b] J ~ 6.0 Hz. [c] Ir
3
6
-1
-1
-1
(potassium bromide) for 22a : 3130 (OH), 1710 (ester CO) cm ; 24c : 3130 (OH), 1675 (CO) cm ; 25a : 1735 (lactone CO), 1715 (ester CO) cm ; 25b:
1740 (lactone CO), 1720 (ester CO) cm . [d] 9-Me protons of 22b, 23b, 24b and 25b appear as singlets at δ 2.31, 2.29, 2.39 and 2.46 ppm, respectively.
-1

1462
C. K. Ghosh, A. Ray and A. Patra
Vol. 38
Table 4
13
C Nmr Data of the 1-Benzopyrano[4,3-b]pyridines 22-24 in DMSO-d and of 25 and 26 in CDCl
6
3
Carbon
22a
22b
22c
23a
23b
23c
24a
24c
25a
25b
26c
No./Type
2
3
4
4a
5
6a
7
8
159.5
124.5
136.5
124.0
91.8
153.8
118.1
132.4
122.7
124.7
120.7
148.0
24.3
159.5
[nd]
136.4
123.9
91.7
151.7
117.9
133.1
131.0
124.6
120.4
148.2
24.9
159.7
124.8
136.7
124.5
92.0
152.4
120.2
131.8
126.1
123.7
122.1
146.6
24.9
159.0
124.1
135.9
123.5
91.7
153.5
117.5
131.8
121.5
124.3
120.3
147.8
24.2
159.5
123.6
136.5
124.6
91.8
151.8
117.9
133.0
130.9
124.6
120.3
148.3
24.8
159.7
124.5
136.7
124.4
92.1
152.5
120.1
131.8
126.1
123.7
122.1
146.7
24.7
157.8
131.4
135.7
124.1
91.7
153.6
117.9
132.0
121.9
124.4
120.7
147.1
24.7
158.0
132.0
135.8
124.3
92.1
152.3
120.0
131.5
126.0
123.5
122.2
145.7
24.6
160.4
125.9
140.7
114.9
166.8
153.4
117.2
132.9
124.9
125.4
118.8
152.7
25.7
160.7
125.6
140.8
114.8
166.7
152.8
117.0
134.0
134.7
125.0
118.2
151.4
25.8
159.6
126.1
140.8
141.9
167.0
151.7
118.7
132.9
130.7
124.7
119.8
151.6
25.7
9
10
10a
10b
2-Me
3-COR
OCH Me
OCH Me
OMe/Me
9-Me
165.8
61.3
14.3
___
165.8
61.3
14.3
___
165.6
61.3
14.2
___
165.9
___
166.2
___
166.0
___
199.9
___
199.8
___
165.0
61.7
14.2
___
165.1
61.7
14.2
___
165.2
___
2
___
___
___
___
___
___
2
51.8
___
52.4
20.5
52.5
___
29.4
___
29.4
___
52.7
___
___
___
___
20.6
20.9
[nd] not detected.
pyridine 9a was crystallised from chloroform-light petroleum,
and 10 and 11 from ethanol.
The mechanism as proposed for the formation of 22 and
23 (Scheme 2) envisages the pyranopyridine 24 to arise from
the treatment of 1 with the preformed enamine 20. This con-
tention was proved to be correct when 24 (Tables 3 and 4)
was indeed formed by treating 1 with a solution of 20
obtained by prior refluxing an ethanolic solution of acetyl-
3-Acetyl-5-(2-hydroxybenzoyl)-2-methylpyridine (9a).
This compound was obtained from 1a and acetylacetone in
64% yield as light yellow crystals, mp and mixed [3] mp 135°;
13
C nmr : δ 199.2, 198.2, 163.2, 161.4, 131.0, 125.0, 123.3 (s),
1
acetone with liquor ammonia for 2 hours. In their H nmr
150.7, 137.0, 136.9, 132.6, 119.2, 118.9 (d), 29.2, 24.6 (q).
spectra in perdeuteriodimethyl sulfoxide, 5-hydroxy protons
of 22-24 appear as doublets at a very low field region (δ
7.40-7.79) due to some kind of their association with the
highly polar solvent whereas that of 24b in deuteriochloro-
form appears as a broadened singlet at δ 3.84 ppm (Table 3).
Treatment of the Acrylic Ester 6 with Ammonia.
A solution of the ester 6 (0.5 mmoles) in ethanol (20 ml) and
liquor ammonia (10 ml) was heated under reflux for 3 hours. The
reaction mixture was then concentrated, diluted with water and
extracted with chloroform. The organic extract was dried over
anhydrous sodium sulphate, concentrated and cooled. The precipi-
tated solid was isolated by filtration and crystallised from chloro-
form-light petroleum to give the product as shining yellow crystals.
This procedure gave 3-acetyl-5-(2-hydroxybenzoyl)pyridin-2-one
(14a) from 6a but ethyl 2-methyl-5-(2-hydroxy-5-methylbenzoyl)-
and 2-methyl-5-(5-chloro-2-hydroxybenzoyl)-pyridine-3-carboxy-
late 13b and 13c from 6b and 6c, respectively. The characterisation
data of the above products are given Tables 1 and 2.
EXPERIMENTAL
Yields and uncorrected melting points of the crystallised prod-
ucts are reported and no attempts were made to optimise the
yield. Nmr and ir spectra were recorded on Bruker AM 300L and
Perkin-Elmer 782 spectrometers, respectively. Light petroleum
refers to the fraction, bp 40-60°.
General Procedure for the Treatment of the Aldehyde 1 with
Acetylacetone, Diethyl Malonate and Ethyl Cyanoacetate.
Ethyl 5-hydroxy-2-methyl-5H[1]benzopyrano[4,3-b]pyridine-3-
carboxylate (22).
The aldehyde 1 (3 mmoles) and the appropriate active methyl-
ene compound 2 (6 mmoles) were dissolved in a mixture of
ethanol (25 ml) and liquor ammonia (10 ml) and the reaction
mixture gently refluxed for 2 hours. An aliquot (10 ml) of liquor
ammonia was added. More alcohol was added, if necessary, to
make the reaction mixture homogeneous. After heating the reac-
tion mixture under reflux for further 2 hours, most of the solvent
was distilled out and the residue cooled. The deposited solid was
collected by filtration and dried. By this procedure 1a gave 9a
with acetylacetone, the pyridines 10 and 11 (Tables 1 and 2)
respectively with diethyl malonate and ethyl cyanoacetate. The
The aldehyde 1a (348 mg, 2 mmoles) and ethyl acetoacetate
(520 mg, 4 mmoles) were refluxed together in ethanol (25 ml)
containing liquor ammonia (10 ml) for 4 hours. The reaction mix-
ture was concentrated, diluted with water, cooled and the
deposited solid isolated by filtration and crystallised from
dimethylformamide - water to give the title pyranopyridine 22a.
The mother liquor after isolation of 22a from the reaction mix-
ture was extracted with chloroform. This extract after usual
work-up did not produce any solid compound. 9-Methyl and
9-chloro substituted analogues of 22a were similarly prepared
from 6b and 6c, respectively (Tables 3 and 4).

Nov-Dec 2001
Benzopyrans. Part 42[1]. Reactions of 4-Oxo-4H-1-benzopyran-3-carbaldehyde
1463
The Pyranopyridine 22a from 1a and Ethyl β-aminocrotonate
(18).
reaction mixture was kept at room temperature for 6-8 hours
and then diluted with water. The deposited solid was collected
by filtration, washed with water, dried and crystallised from
chloroform. By this procedure the pyridines 22 and 23 were
oxidised respectively to ethyl and methyl 2-methyl-5-oxo-
5H[1]benzopyrano[4,3-b]pyridine-3-carboxylate 25 and 26
(Tables 3 and 4).
A solution of 1a (348 mg, 2 mmoles) and 18 (323 mg, 2.5
mmoles) in ethanol (25 ml) was heated under reflux for 3 hours.
Usual work-up of the reaction mixture gave 22a (342 mg, 60%)
identical (mp, mixed mp and superimposable ir) with that previ-
ously obtained by treating 1a with ethyl acetoacetate and ammonia.
Acknowledgement.
Methyl 5-Hydroxy-2-methyl-5H-[1]benzopyrano[4,3-b]pyri-
dine-3-carboxylate (23).
Financial assistance from CSIR, New Delhi [Scheme No.
01(1622)/EMR-II] is duly acknowledged.
The substrate 1 dissolved in methanol was treated with methyl
acetoacetate similarly as previously described for the treatment of
1 with ethyl acetoacetate in the presence of ammonia to afford the
ester 23, the characterisation data of the product crystallised from
dimethylformamide-water being presented in Tables 3 and 4.
REFERENCES AND NOTES
[1] Part 41 : C. K. Ghosh, S. Bhattacharyya and A. Patra, J.
Chem. Soc., Perkin Trans. 1, 3005 (1999).
3-Acetyl-5-hydroxy-2-methyl-5H-[1]benzopyrano[4,3-b]pyri-
dine (24).
[2] For reviews see C. K. Ghosh, J. Heterocyclic Chem., 20,
1437 (1983); G. Sabitha, Aldrichimica Acta, 29, 15 (1996).
[3] C. K. Ghosh and S. Khan, Synthesis, 903 (1981).
[4] M. Satyanarayana Reddy, G. L. David Krupadanam and
G. Srimannarayana, Indian J. Chem., 29B, 978 (1990).
[5] A. Nohara, T. Ishiguro and Y. Sanno, Tetrahedron Lett.,
1183 (1974).
[6] D. Heber, Synthesis, 691 (1978); Pharm. Z., 123, 1650
(1978).
[7] G. Haas, J. L. Stanton, A. von Sprecher and P. Wenk, J.
Heterocyclic Chem., 18, 607 (1981).
[8] W. D. Jones and W. L. Albrecht, J. Org. Chem., 41, 706
(1976).
[9] C. K. Ghosh, C. Bandyopadhyay, S. Biswas and A. K.
Chakravarty, Indian J. Chem., 29B, 814 (1990); C. K. Ghosh, S.
Sahana and C. Bandyopadhyay, Indian J. Chem., 32B, 624 (1993).
A solution of acetylacetone (~ 1.0 g, 10 mmoles) and liquor
ammonia (15 ml) in ethanol (25 ml) was refluxed for 2 hours.
Then 1a (522 mg, 3 mmoles) dissolved in ethanol (25 ml) was
added to the above solution. The reaction mixture was heated
under reflux for 3 hours, concentrated by distilling out most of
the alcohol, diluted with water and cooled. The deposited solid
was isolated by filtration and crystallised from dimethylfor-
mamide - water to afford the title pyridine 24a, its two other ana-
logues 24b and 24c (Tables 3 and 4) being similarly prepared
from 1b and 1c, respectively.
General Procedure for Oxidation of the Pyridines 22 and 23.
Chromium trioxide (~ 30 mg) was added to 22 or 23 (70-100
mg) dissolved in minimum amount of glacial acetic acid. The