Synthesis of 2-substituted-4H-pyrido[2,3-h]benzoxazin-4-ones and 2-substituted pyrido[2,3-h]-quinazolin-4(3H)ones

Article abstract of DOI:10.1081/SCC-120005995

The reaction of 2-substituted-4H-pyrido[2,3-h]benzoxazin-4-ones (1) with hydrazine hydrate resulted in 2-substituted-3-aminopyrido[2,3-h]quinazolin-4(3H)ones (2) and not in the corresponding 3. The Schiff bases (4) of 2 on pyrolysis led to 2-substituted pyrido[2,3-h]quinazolin-4(3H)ones (5).

Full text of DOI:10.1081/SCC-120005995

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SYNTHESIS OF 2-SUBSTITUTED-4H-PYRIDO[2,3-
h]BENZOXAZIN-4-ONES AND 2-SUBSTITUTED
PYRIDO[2,3-h]-QUINAZOLIN-4(3H)ONES
T. Aruna Kumari a & P. Jayaprasad Rao b
a Department of Chemistry , Osmania University , Hyderabad, A.P., 500007, India
b Department of Chemistry , Osmania University , Hyderabad, A.P., 500007, India
Published online: 16 Aug 2006.
To cite this article: T. Aruna Kumari & P. Jayaprasad Rao (2002) SYNTHESIS OF 2-SUBSTITUTED-4H-PYRIDO[2,3-
h]BENZOXAZIN-4-ONES AND 2-SUBSTITUTED PYRIDO[2,3-h]-QUINAZOLIN-4(3H)ONES, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 32:15, 2261-2267, DOI: 10.1081/
SCC-120005995
To link to this article: http://dx.doi.org/10.1081/SCC-120005995
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SYNTHETIC COMMUNICATIONS
Vol. 32, No. 15, pp. 2261–2267, 2002
SYNTHESIS OF 2-SUBSTITUTED-4H-
PYRIDO[2,3-h]BENZOXAZIN-4-ONES AND
2-SUBSTITUTED PYRIDO[2,3-h]-
QUINAZOLIN-4(3H)ONES
*
T. Aruna Kumari and P. Jayaprasad Rao
Department of Chemistry, Osmania University,
Hyderabad-500007, A.P. India
ABSTRACT
The reaction of 2-substituted-4H-pyrido[2,3-h]benzoxazin-4-
ones (1) with hydrazine hydrate resulted in 2-substituted-3-
aminopyrido[2,3-h]quinazolin-4(3H)ones (2) and not in the
corresponding 3. The Schiff bases (4) of 2 on pyrolysis led to
2-substituted pyrido[2,3-h]quinazolin-4(3H)ones (5).
The potentiality of 5-aminoquinoline-6-carboxylic acid[1] has not been
explored fully. It has been used by us earlier in the synthesis of 2,3-disub-
stituted pyrido[2,3-h]benzoxazin-4-ones.[2] The results of 2-substituted-
4H-benzoxazin-4-one and hydrazine hydrate[3–7] have been debated earlier.
This prompted us to take up the investigation of 2-substituted-4H-
pyrido[2,3-h]benzoxazin-4-one and hydrazine hydrate reaction and the
results with spectral, analytical and chemical evidence are presented
hereunder (Tables 1 and 2).
*Corresponding author.
2261
DOI: 10.1081/SCC-120005995
Copyright & 2002 by Marcel Dekker, Inc.
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2262
ARUNA KUMARI AND JAYAPRASAD RAO
Table 1. Characterisation Data of 2, 4, and 5
M.P.
(ꢀC)
Yield
(%)
Compound
Ar
Ar1
2a
2b
2c
2d
2e
2f
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4q
4r
5a
5b
5c
5d
5e
5f
C6H5
–
–
–
–
–
–
252–253
258
248–250
276–278
206
242
242
216–219
214
252
228
254
244
226–227
236
262
228–230
254
196
52
61
57
58
60
63
62
61
55
52
56
59
64
62
59
61
62
56
64
61
66
60
59
65
61
63
58
55
65
66
4-CH3–C6H4
4-OCH3–C6H4
4-Cl–C6H4
C2H5
CH3
C6H5
C6H5
C6H5
C6H5
4-CH3–C6H4
4-OCH3–C6H4
C6H5
4-CH3–C6H4
4-OCH3–C6H4
C6H5
4-CH3–C6H4
4-OCH3–C6H4
C6H5
4-CH3–C6H4
4-OCH3–C6H4
C6H5
4-CH3–C6H4
4-OCH3–C6H4
C6H5
4-CH3–C6H4
4-OCH3–C6H4
–
4-CH3–C6H4
4-CH3–C6H4
4-CH3–C6H4
4-OCH3–C6H4
4-OCH3–C6H4
4-OCH3–C6H4
4-Cl–C6H4
4-Cl–C6H4
4-Cl–C6H4
C2H5
C2H5
C2H5
CH3
CH3
CH3
C6H5
4-CH3–C6H4
4-OCH3–C6H4
4-Cl–C6H4
C2H5
184–185
210
207
205
248–251
> 300
> 300
> 300
> 300
268
–
–
–
–
CH3
–
> 300
The reaction of 2-p-tolyl-4H-pyrido[2,3-h]benzoxazin-4-one (1, Ar ¼
4-CH3–C6H4) with an excess of hydrazine hydrate under refluxing condition
for 2 h gave a crystalline compound with m.p. 258ꢀC. The mass spectrum of
1
the compound revealed the molecular ion at m/z 302. The H-NMR spec-
trum (DMSO–d6) exhibited signals at ꢀ 2.4 (s, 3H, CH3), 5.9 (s, 2H, NH2,
D2O exchangeable), 7.3 (d, 2H, Ar–H, H7, H8), 7.7 (m, 1H, Ar–H, H4), 7.9
(m, 3H, Ar–H, H2, H6, H9), 8.1 (d, 1H, Ar–H, H5), 9.1 (d, 1H, Ar–H, H1),
9.3 (d, 1H, Ar–H, H3). Based on the elemental analysis and spectral data the

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2-SUBSTITUTED-4H-PYRIDO[2,3-h]BENZOXAZIN-4-ONES
2263
Table 2. Analytical Data of 2, 4, and 5
Found % (Calc.)
Comp.
Mol. Formula
C
H
N
2a
2b
2c
2d
2e
2f
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4q
4r
5a
5b
5c
5d
5e
5f
C17H12N4O
C18H14N4O
C18H14N4O2
C17H11N4ClO
C13H12N4O
C12H10N4O
C24H16N4O
C25H18N4O
C25H18N4O2
C25H18N4O
C26H20N4O
C26H20N4O2
C25H18N4O2
C26H20N4O2
C26H20N4O3
C24H15N4ClO
C25H17N4ClO
C25H17N4ClO2
C20H16N4O
C21H18N4O
C21H18N4O2
C19H14N4O
C20H16N4O
C20H16N4O2
C17H11N3O
C18H13N3O
C18H13N3O2
C17H10N3ClO
C13H11N3O
C12H9N3O
70.84 (70.83)
71.50 (71.52)
67.91 (67.92)
63.23 (63.26)
65.02 (65.00)
63.68 (63.72)
76.62 (76.60)
76.93 (76.92)
73.85 (73.89)
76.91 (76.92)
77.20 (77.22)
74.27 (74.29)
73.88 (73.89)
74.30 (74.29)
71.54 (71.56)
70.19 (70.16)
70.65 (70.67)
68.11 (68.10)
73.20 (73.17)
73.65 (73.68)
70.36 (70.39)
72.62 (72.61)
73.18 (73.17)
69.76 (69.77)
74.71 (74.73)
75.27 (75.26)
71.30 (71.29)
66.32 (66.34)
69.32 (69.33)
68.27 (68.25)
4.16 (4.17)
4.61 (4.64)
4.42 (4.40)
3.39 (3.41)
4.99 (5.00)
4.44 (4.42)
4.25 (4.26)
4.60 (4.62)
4.41 (4.43)
4.61 (4.62)
4.94 (4.95)
4.75 (4.76)
4.40 (4.43)
4.72 (4.76)
4.58 (4.59)
3.66 (3.65)
4.01 (4.00)
3.85 (3.86)
4.89 (4.88)
5.24 (5.26)
5.01 (5.03)
4.41 (4.46)
4.85 (4.88)
4.63 (4.65)
4.01 (4.03)
4.52 (4.53)
4.26 (4.29)
3.23 (3.25)
4.85 (4.89)
4.22 (4.27)
19.42 (19.44)
18.57 (18.54)
17.60 (17.61)
17.33 (17.36)
23.34 (23.30)
24.75 (24.78)
14.90 (14.89)
14.35 (14.36)
13.81 (13.79)
14.35 (14.36)
13.87 (13.86)
13.33 (13.33)
13.80 (13.79)
13.32 (13.33)
12.85 (12.84)
13.61 (13.64)
13.20 (13.19)
12.73 (12.71)
17.08 (17.07)
16.38 (16.37)
15.65 (15.64)
17.84 (17.83)
17.08 (17.07)
16.26 (16.28)
15.35 (15.38)
14.61 (14.63)
13.88 (13.86)
13.65 (13.66)
18.61 (18.67)
19.88 (19.91)
compound was assigned the structure 2-p-tolyl-3-aminopyrido[2,3-h]quina-
zolin-4(3H)one (2b). An alternate pyridobenzotriazepin-5-one structure
(3, Ar ¼ 4-CH3–C6H4) for this compound is ruled out based on the presence
of a doublet around 3250 cmÀ1 corresponding to NH2 in its IR spectrum
1
(KBr) and also a two proton D2O exchangeable singlet at ꢀ 5.9 in its H-
NMR spectrum.
The reaction has been extended to other 2-aryl-4H-pyrido[2,3-h]ben-
zoxazin-4-ones (1) and in each case the product was identified as the

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2264
ARUNA KUMARI AND JAYAPRASAD RAO
Scheme 1.
corresponding 2-aryl-3-aminopyrido[2,3-h]quinazolin-4(3H)-one (2) based
on spectral and analytical data (Scheme 1).
The formation of 2 from 1 probably involves nucleophilic attack by
hydrazino nitrogen on carbonyl carbon of the latter, resulting in an open
chain intermediate.[6,8] Subsequent loss of elements of water from the
tautomeric form of the intermediate involving NH and not NH2 yields
compound 2. Compounds 2 were also obtained from 1 and hydrazine
hydrate under variety of conditions like hot acetic acid, refluxing methanol,
xylene and pyridine.
Further proof for the structure assigned to compound 2 came from the
fact that it formed a Schiff base (4) with aromatic aldehyde. Compound 4
1
was characterised by the presence of an azomethine signal in its H-NMR
spectrum (DMSO–d6, Table 3) and characteristic (Mþꢁ –H) peak in its
mass spectrum. To ascertain the generality, all the 2 were treated indepen-
dently with benzaldehyde, 4-methylbenzaldehyde and 4-methoxybenzalde-
hyde. In each case the corresponding 4 were characterised by spectral and
analytical data.
The N–N bond is considered to be labile and susceptible to cleavage.
To verify this, 2-p-tolyl-3-benzylidene aminopyrido[2,3-h]quinazolin-4(3H)-
one (4d) was subjected to neat pyrolysis above its melting point.
The reaction mixture on processing afforded the benzonitrile and a com-
pound with molecular ion at m/z 287. The IR spectrum (KBr) showed the
presence of NH (broad at 3200 cmÀ1), amide C¼O (at 1658 cmÀ1) and C¼N

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2-SUBSTITUTED-4H-PYRIDO[2,3-h]BENZOXAZIN-4-ONES
2265
Table 3. 1H-NMR Data of Selected 2, 4, and 5 (DMSO–d6)
Compound
2a
Data (ꢀ)
5.7 (s, 2H, NH2, D2O exchangeable), 7.3–7.5 (m, 5H, c-phenyl),
7.7 (m, 1H, Ar–H, H4), 7.9 (m, 2H, Ar–H, H2, H5), 9.1 (d, 1H,
Ar–H, H1), 9.4 (d, 1H, Ar–H, H3).
2c
2e
3.7 (s, 3H, OCH3), 5.9 (s, 2H, NH2, D2O exchangeable), 7.2 (d,
2H, Ar–H, H7, H8), 7.7 (m, 1H, Ar–H, H4), 7.9 (m, 3H, Ar–H, H2,
H6, H9), 8.0 (d, 1H, Ar–H, H5), 9.2 (d, 1H, Ar–H, H1), 9.3 (d, 1H,
Ar–H, H3).
1.1 (t, 3H, CH3 of ethyl), 1.3 (q, 2H, CH2 of ethyl), 5.8 (s, 2H,
NH2, D2O exchangeable), 7.3 (d, 2H, Ar–H, H7, H8), 7.7 (m, 1H,
Ar–H, H4), 7.9 (m, 3H, Ar–H, H2, H6, H9), 8.1 (d, 1H, Ar–H, H5),
9.1 (d, 1H, Ar–H, H1), 9.3 (d, 1H, Ar–H, H3).
4b
4c
4n
2.4 (s, 3H, CH3), 7.7 (m, 1H, Ar–H, H4), 7.2–7.6 (m, 9H, Ar–H,
phenyl & p-tolyl), 8.1 (d, 1H, Ar–H, H2), 8.4 (d, 1H, Ar–H, H5),
9.1 (s, 2H, Ar–H, H1 and azomethine), 9.3 (d, 1H, Ar–H, H3).
3.9 (s, 3H, OCH3), 7.8 (m, 1H, Ar–H, H4) 7.2–7.5 (m, 9H, Ar–H,
phenyl & anisyl), 8.2 (d, 1H, Ar–H, H2) 8.4 (d, 1H, Ar–H, H5), 9.2
(s, 2H, Ar–H, H1 and azomethine), 9.3 (d, 1H, Ar–H, H3).
1.1 (t, 3H, CH3 of ethyl), 1.3 (q, 2H, CH2 of ethyl), 2.5 (s, 3H,
CH3), 7.8 (m, 1H, Ar–H, H4), 7.4 (m, 4H, Ar–H, p-tolyl), 8.1 (d,
1H, Ar–H, H2), 8.4 (d, 1H, Ar–H, H5), 9.1 (s, 2H, Ar–H, H1 and
azomethine), 9.2 (d, 1H, Ar–H, H3).
5a
5c
7.3 (s, 1H, NH2, D2O exchangeable), 7.5 (m, Ar–H of phenyl), 8.2
(m, 1H, Ar–H, H2), 8.4 (d, 1H, Ar–H, H4), 8.7 (d, 1H, Ar–H, H5),
9.3 (m, 2H, Ar–H, H1, H3).
3.8 (s, 3H, OCH3), 7.1 (s, 1H, NH, D2O exchangeable), 7.2 (d, 2H,
Ar–H, H7, H8), 7.7 (m, 1H, Ar–H, H4), 7.8 (m, 3H, Ar–H, H2, H6,
H9), 8.2 (d, 1H, Ar–H, H5), 9.1 (d, 1H, Ar–H, H1), 9.3 (d, 1H,
Ar–H, H3).
1
(at 1599 cmÀ1). The H-NMR spectrum (DMSO–d6) exhibited signals at
ꢀ 2.4 (s, 3H, CH3), 7.2 (s, 1H, NH, D2O exchangeable), 7.5 (d, 2H, Ar–H,
H7, H8), 8.2 (m, 3H, Ar–H, H2, H6, H9), 8.4 (d, 1H, Ar–H, H4), 8.7 (d, 1H,
Ar–H, H5) and 9.4 (m, 2H, Ar–H, H1, H3). Based on the spectral
and analytical data the compound has been characterised as 2-p-tolyl-
pyrido[2,3-h]quinazolin-4(3H)-one (5b). Similarly all the 4 on pyrolysis
afforded the corresponding arylnitrile and 5.
Formation of 5 and arylnitrile from 4 probably involves a six-
membered cyclic transition state involving H-transfer and the N–N bond
cleavage. Compounds 5 were also obtained from 2 in the presence of

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ARUNA KUMARI AND JAYAPRASAD RAO
KMnO4 and dry acetone under refluxing conditions. In this reaction, the
compound 2 undergoes oxidative coupling to give dipyridoquinazolinyl
hydrazine[9] followed by the loss of nitrogen through a six-membered
cyclic transition state to yield 5. Reaction of 1 with an excess of ammonia
under refluxing conditions also afforded 5.
EXPERIMENTAL SECTION
2-Substituted-3-aminopyrido[2,3-h]quinazolin-4(3H)ones (2): A mixture
of 2-substituted-4H-pyrido[2,3-h]benzoxazin-4-one (1, 10 mmol) and hydra-
zine hydrate (99%, 5 mL) was heated under reflux for 2 h, cooled and diluted
with water. The compound (2) that separated was filtered, washed with a
few drops of alcohol and dried.
2-Substituted-3-arylidene aminopyrido[2,3-h]quinazolin-4(3H)-ones (4):
A mixture of 2 (1 mmol) and aromatic aldehyde (1 mmol) in ethanol
(5 mL) was warmed on steam bath for 15 min and cooled to give crystalline 4.
2-Substituted pyrido[2,3-h]quinazolin-4(3H)-ones (5): 1 mmol of 4 was
heated 20ꢀC above its melting point for 1 h. Later it was dissolved in chloro-
form and subjected to chromatography. Elution with benzene–ethylacetate
(1 : 1) mixture yielded pure 5.
Oxidation of 2-substituted-3-aminopyrido[2,3-h]quinazolin-4(3H)ones
(2) to give 5.
Compounds 2 were oxidised by KMnO4 following a similar oxidation
reaction reported in literature.[9]
ACKNOWLEDGMENTS
One of the authors (TAK) is thankful to UGC (New Delhi) for the
award of a Senior Research Fellowship.
REFERENCES
1. Bogert, M.T.; Fisher, H.L. J. Am. Chem. Soc. 1912, 34, 1570.
2. Aruna Kumari, T.; Satyanarayana Reddy, M.; Jayaprasad Rao, P.
Synth. Commun., in press, 2001.
3. Reddy, C.K.; Reddy, P.S.N.; Ratnam, C.V. Ind. J. Chem. 1985, 24, 902.
4. Peet, N.P. Synthesis 1984, 1065.
5. Reddy, C.K.; Reddy, P.S.N.; Ratnam, C.V. Synthesis 1983, 10, 842.

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2-SUBSTITUTED-4H-PYRIDO[2,3-h]BENZOXAZIN-4-ONES
2267
6. Scheiner, P.; Frank, L.; Giusti, I.; Arwin, S. J. Heterocycl. Chem. 1984,
21, 1817.
7. Leiby, R.W. J. Heterocycl. Chem. 1984, 21, 1825.
8. Mahesh Reddy, G.; Reddy, P.S.N. Ind. J. Chem. 1997, 36, 166.
9. Radha, K.V.; Venkateswara Rao, B.; Kaushik, B.; Singh, S.P. Ind. J.
Chem. 1987, 26, 376.
Received in the UK June 8, 2001

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