Microwave assisted synthesis of imidazo[1,2-a][1,8]Naphthyridin-1(2H)-ones

Article abstract of DOI:10.1081/SCC-120002694

Synthesis of 2-carboxyalkylamino-3-(p-chlorophenyl)-1,8-naphthyridines and their conversion into novel imidazo [1,2-a][1,8]naphthyridin-1(2H)-ones under microwave irradiation are described.

Full text of DOI:10.1081/SCC-120002694

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MICROWAVE ASSISTED SYNTHESIS OF IMIDAZO[1,2-a]-
[1,8]NAPHTHYRIDIN-1(2H)-ONES
K. Mogilaiah a , D. Srinivasa Chowdary a & P. Raghotham Reddy a
a Department of Chemistry , Kakatiya University , Warangal, 506 009, India
Published online: 16 Aug 2006.
To cite this article: K. Mogilaiah , D. Srinivasa Chowdary & P. Raghotham Reddy (2002) MICROWAVE ASSISTED SYNTHESIS
OF IMIDAZO[1,2-a]- [1,8]NAPHTHYRIDIN-1(2H)-ONES, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 32:6, 857-862, DOI: 10.1081/SCC-120002694
To link to this article: http://dx.doi.org/10.1081/SCC-120002694
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SYNTHETIC COMMUNICATIONS, 32(6), 857–862 (2002)
MICROWAVE ASSISTED SYNTHESIS
OF IMIDAZO[1,2-a]-
[1,8]NAPHTHYRIDIN-1(2H)-ONES
*
K. Mogilaiah, D. Srinivasa Chowdary,
and P. Raghotham Reddy
Department of Chemistry, Kakatiya University,
Warangal-506 009, India
ABSTRACT
Synthesis of 2-carboxyalkylamino-3-( p-chlorophenyl)-1,8-
naphthyridines and their conversion into novel imidazo
[1,2-a][1,8]naphthyridin-1(2H)-ones under microwave irradia-
tion are described.
In recent years the use of microwave irradiation in organic reactions is
rapidly increasing because of the short reaction time, operational simplicity
and formation of cleaner reaction products. It has been commonly
employed as thermal energy source in various organic reactions.1 The use
of domestic microwave oven in this regard is now a well-established
procedure in MORE2 chemistry. 1,8-Naphthyridines3 and imidazoles4
reported in the literature were found to possess varied biodynamic proper-
ties. In view of this and in continuation of our interest in developing simple
and efficient routes for the synthesis of fused 1,8-naphthyridines,5 we report
herein the microwave assisted synthesis of a novel and hitherto unknown
*Corresponding author.
857
Copyright & 2002 by Marcel Dekker, Inc.
www.dekker.com

858
MOGILAIAH, CHOWDARY, AND REDDY
bridgehead nitrogen heterocyclic system viz., imidazo [1,2-a] [1,8]naph-
thyridin-1(2H)-ones.
The reaction of 2-amino-3-( p-chlorophenyl)-1,8-naphthyridine 15f
with HNO2 afforded 1,2-dihydro-3-( p-chlorophenyl)-1,8-naphthyridin-2-
one 2. Treatment of 2 with POCl3 in microwave oven furnished 2-chloro-
3-( p-chlorophenyl)-1,8-naphthyridine 3.
Scheme 1.
Interaction of 3 with a-aminoacids in glacial acetic acid under micro-
wave irradiation yielded the corresponding 2-carboxyalkylamino-3-( p-
chlorophenyl)-1,8-naphthyridines 4. Compounds 4 on treatment with
POCl3 under microwave irradiation resulted in the formation of imidazo-
[1,2-a][1,8]naphthyridin-1(2H)-ones 5 (Scheme 1).
The microwave procedure for transformation of 4 to 5 owes its
importance due to the fact that the reaction is completed within 5 min
with improved yield as compared to conventional heating which
requires 6–7 h.

IMIDAZO[1,2-a][1,8]NAPHTHYRIDIN-1(2H)-ONES
859
Incidentally, this is the first observation of microwave irradiated
synthesis of fused 1,8-naphthyridines.
In conclusions, the present method provides a highly efficient and
practical synthesis of fused 1,8-naphthyridines with following advantages:
significant shortening of the reaction time, simple reaction conditions and
high yields of the products.
EXPERIMENTAL
IR spectra were recorded in KBr on a Perkin-Elmer spectrum BX
series FT-IR spectrometer. The 1H NMR spectra were recorded on a
Varian Gemini 200 MHz instrument and the chemical shifts were reported
with Me4Si as an internal standard. Mass spectra (MS) were measured on a
Jeol JMSD-300 spectrometer. Microwave reactions were carried out in BPL
make domestic microwave oven model No 800 G operating at 2450 MHz.
1,2-Dihydro-3-( p-chlorophenyl)-1,8-naphthyridin-2-one 2
To a cold solution of 1 (2.55 g, 0.01 mol) in 2N HCl (25 ml) was added
NaNO2 solution (0.01 mol in 25 ml water) and the reaction mixture stirred at
room temperature for 0.5 h. It was then treated with chilled water. The solid
that precipitated was filtered, washed with water and recrystallized from
methanol to give 2 (2.20 g, 86%) as a pale yellow compound, m.p. 284ꢀC.
IR (KBr) 3448, 1672, 1607 cmꢁ1. 1H NMR (DMSO-d6) d 7.27–7.83 (m, 5H,
C6-H, 4 Ar-H); 8.18 (m, 2H; C4-H, C5-H); 8.56 (m, 1H, C7-H); 12.42 (s, 1H,
NH). EIMS m/z Mþ 256 (100%). Anal. Calcd for C14H9N2OC1: C, 65.50;
H, 3.51; N, 10.92. Found: C, 65.72; H, 3.60; N, 10.82.
2-Chloro-3-( p-chlorophenyl)-1,8-naphthyridine 3
A mixture of 2 (2.56 g, 0.01 mol) and POCl3 (20 ml) was irradiated in
microwave oven for 3 min, the completion of the reaction was monitored by
tlc. The reaction mixture was then added to crushed ice and NaHCO3. The
precipitated product was filtered, washer with water and recrystallized from
ethanol to afford 3 (2.41 g, 88%) as a white compound, m.p. 262ꢀC. IR
1
(KBr) 1603 cmꢁ1. H NMR (DMSO-d6) d 7.67–7.81 (m, 5H, C6-H, 4Ar-
H); 8.22 (m, 1H, C4-H); 8.62 (m, 1H, C5-H); 9.20 (m, 1H, C7-H). EIMS
m/z Mþ 274 (100%). Anal. Calcd. for C14H8N2Cl2: C, 61.09; H, 2.91; N,
10.18. Found: C, 61.28; H, 2.83; N, 10.26.

860
MOGILAIAH, CHOWDARY, AND REDDY
2-Carboxymethylamino-3-( p-chlorophenyl)-1,8-naphthyridine 4a
A mixture of 3 (2.74 g, 0.01 mol) and glycine (0.75 g, 0.01 mol) in gla-
cial acetic acid (20 ml) was subjected to microwave irradiation for 4 min, the
completion of the reaction was monitored by tlc and poured on crushed ice.
The crude product was separated by filtration and recrystallized from
methanol to furnish 4a (2.82 g, 90%) as a white crystalline compound,
m.p. 280ꢀC. IR (KBr) 3420, 3150, 2960, 2887, 1672, 1608 cmꢁ1. H NMR
1
(DMSO-d6) d 3.82 (s, 2H, CH2); 7.27–7.85 (m, 6H, C6-H, 4Ar-H, NH); 8.18
Table 1. Analytical Data of the Compounds 4 and 5
Analysis Calc./Found
Product
No.
M.P. Yield
(ꢀC) (%)
R
Mol.Form
C%
H%
N%
4a
4b
4c
4d
4e
4f
H
280
275
273
279
90 C16H12N3O2Cl 61.24
3.83
3.90
4.27
4.32
5.06
5.12
5.41
5.50
5.41
5.51
4.46
4.53
4.29
4.37
3.38
3.45
3.88
3.95
4.74
4.80
5.12
5.20
5.12
5.19
4.15
4.20
3.98
3.89
13.40
13.51
12.82
12.95
11.81
11.95
11.37
11.48
11.37
11.47
10.41
10.54
10.01
10.15
14.21
14.29
13.57
13.66
12.44
12.52
11.95
11.86
11.95
11.84
10.89
10.78
10.46
10.57
61.40
94 C17H14N3O2Cl 62.29
62.43
92 C19H18N3O2Cl 64.13
64.30
90 C20H20N3O2Cl 64.95
64.78
91 C20H20N3O2Cl 64.95
64.77
86 C23H18N3O2Cl 68.40
68.61
88 C23H18N3O3Cl 65.79
65.95
CH3
(CH3)2CH
(CH3)2CHCH2
CH3CH2CHCH3 276
PhCH2
273
280
232
195
240
4g
5a
5b
5c
5d
5e
5f
p-HOC6H4CH2
H
86
90
87
C16H10N3OCl 64.97
64.81
C17H12N3OCl 65.91
65.73
C19H16N3OCl 67.55
67.71
CH3
(CH3)2CH
(CH3)2CHCH2
>300 86
C20H18N3OCl 68.28
68.40
CH3CH2CHCH3 230
84
83
C20H18N3OCl 68.28
69.39
C23H16N3OCl 71.59
71.77
PhCH2
215
270
5g
p-HOC6H4CH2
85 C23H16N3O2Cl 68.74
68.90

IMIDAZO[1,2-a][1,8]NAPHTHYRIDIN-1(2H)-ONES
861
(m, 2H, C4-H, C5-H); 8.57 (m, 1H, C7-H); 12.40 (s, 1H, COOH). EIMS m/z
Mþ 313 (23.1%). Anal. Calcd for C16H12N3O2Cl: C, 61.24; H, 3.83; N,
13.40. Found: C, 61.40; H, 3.90; N, 13.51. Compound 4b–g were similarly
prepared (Table 1).
4-( p-Chlorophenyl)-imidazo[1,2-a][1,8]naphthyridin-1(2H)-one 5a
A mixture of 4a (3.13 g, 0.01 mol) and POCl3 (10 ml) was irradiated in
microwave oven till the cyclization was over (about 5 min; by tlc) and
poured on crushed ice. The product which separated on neutralisation
with NaHCO3 was filtered, washed with water and recrystallized from
methanol to give 5a (2.54 g, 86%) as a white compound, m.p. 232ꢀC. IR
(KBr) 1656, 1600 cmꢁ1. 1H NMR (DMSO-d6) d 4.22 (s, 2H, CH2); 7.42–7.84
(m, 5H, C7-H, 4Ar-H); 8.59 (m, 1H, C5-H); 8.73 (m, 1H, C6-H); 9.14 (m, 1H,
C8-H). EIMS m/z Mþ 295 (9.9%). Anal. Calcd for C16N10N3OCl: C, 64.97;
H, 3.38; N, 14.21. Found: C, 64.81; H, 3.45; N, 14.29. Compounds 5b–g
were prepared similarly (Table 1).
ACKNOWLEDGMENT
We wish to thank University Grants Commission, New Delhi, India
for the award of a Research Fellowship to DSC under Faculty Improvement
Programme.
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862
MOGILAIAH, CHOWDARY, AND REDDY
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Accepted for publication (OC-7547).
Received in Japan January 9, 2001