Synthesis of 11H-pyrido[2,1-b]quinazolin-11-one and derivatives using ultrasound irradiation

Article abstract of DOI:10.1081/SCC-120018939

An improved synthesis of 11H-pyrido[2,1-b]quinazolin-11-one and derivatives, by the condensation of 2-chlorobenzoic acid and 2-aminopyridine derivatives in N,N-dimethylformamide (DMF) is reported using ultrasound irradiation. The derivatives were prepared

Full text of DOI:10.1081/SCC-120018939

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Synthesis of 11H-Pyrido[2,1-b]quinazolin-11-one and
Derivatives Using Ultrasound Irradiation
Maite L. Docampo Palacios a & Rolando F. Pellón Comdom a
a Centro de Química Farmacéutica , La Habana, Cuba
Published online: 17 Aug 2006.
To cite this article: Maite L. Docampo Palacios & Rolando F. Pellón Comdom (2003) Synthesis of 11H-Pyrido[2,1-
b]quinazolin-11-one and Derivatives Using Ultrasound Irradiation, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 33:10, 1777-1781
To link to this article: http://dx.doi.org/10.1081/SCC-120018939
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 10, pp. 1777–1781, 2003
Synthesis of 11H-Pyrido[2,1-b]quinazolin-11-one
and Derivatives Using Ultrasound Irradiation
*
Maite L. Docampo Palacios and Rolando F. Pellon Comdom
Centro de Quımica Farmaceutica, La Habana, Cuba
ABSTRACT
An improved synthesis of 11H-pyrido[2,1-b]quinazolin-11-one
and derivatives, by the condensation of 2-chlorobenzoic acid and
2-aminopyridine derivatives in N,N-dimethylformamide (DMF) is
reported using ultrasound irradiation. The derivatives were prepared
in good yield and in a short reaction time.
In a previous communication[1] we reported the use of N,N-dimethyl-
formamide as solvent in the Ullmam-Goldberg condensation of 2-chloro-
benzoic acid (I) with 2-aminopyridine (II) for the synthesis of
11H-pyrido[2,1-b]quinazolin-11-one (IV). This reaction proceeds through
*Correspondence: Rolando F. Pellon Comdom, Centro de Quımica
Farmaceutica, Apartado 16042, La Habana, Cuba; Fax: (537) 336471; E-mail:
pellonrf@cqf.co.cu.
1777
DOI: 10.1081/SCC-120018939
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

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1778
Docampo Palacios and Pellon Comdom
the corresponding 2-(2-pyridilamine) benzoic (III) acid which cyclizes in
the reaction medium.
The conditions studied for the condensation used one equivalent of
potassium carbonate, 2 equivalents of amine, 3% Cu (in weight) per mol
of 2-chlorobenzoic acid and dimethylformamide as solvent.
Recently, an interesting series of substituted l1H-pyrido[2,1-b]quina-
zolin-11-ones has been studied as antiallergic,[2] cell protectants[3] and
hypolipemic agents.[4]
In the present communication, we describe the use of ultrasound
irradiation in the synthesis of 11H-pyrido[2,1-b]quinazohn-11-one
derivatives, in order to shorten reaction times.
RESULTS AND DISCUSSION
First, we studied the effect of ultrasonic irradiation on the reaction rate
for the synthesis of 11-pyrido[2,1-b]quinazolin-11-one, obtained by con-
densation of 2-chlorobenzoic acid with 2-aminopyridine in DMF (Table 1).
The best yield was obtained at 20min reaction time, when we used more
than 20min the yield remained constant, which was confirmed by standard
deviation values. All experiments were repeated five times. The yields
reported represent an average of the obtained values for each reaction.
Table 1. Ultrasonic irradiation in synthesis of 11H-pyrido[2,1-b]quinazolin-11-
one: yield dependance on time.
Ultrasonic irradiation
time (min)
Yield of 11H-pyrido[2,1-b]-
quinazolin-11-one (%)
Standard
deviation (S)
30
25
20
15
72
71
71
56
1.5
1.0
1.5
1.5

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Synthesis of 11H-Pyrido[2,1-b]quinazolin-11-one
1779
Table 2. Results using ultrasound irradiation (20 min) vs. reflux (6 h) in DMF
as solvent.
% Yield using
ultrasound
(20 min)
% Yield in 6 h at
refluxing in DMF
as solvent
No.
Substituent
m/e
1
2
3
4
5
6
7
8
9
R1¼R2¼R3¼R4¼R5¼H
R4¼CH3
75
82
69
79
65
67
78
89
63
64
77
48
72
49
52
72
84
25
196
210
210
226
330
241
241
286
241
R5¼CH3
R1¼OCH3
R2¼Cl
R3¼NO2
R1¼NO2
R1¼R3¼NO2
R2¼NO2
In Table 2 we compare the results using ultrasound irradiation
(20 min) vs. reflux (6 h). In all cases the yield obtained using ultrasound
is superior. It is interesting to mention that in the case of Entry 3, the
2-[(6-methyl-3-pyridinyl)amino]benzoic acid was obtained with reflux.
This acid was cycled using sulfuric acid at 100ꢀC to the corresponding
9-methyl-11H-pyrido[2,1-b]quinazolin-11-one. Employing ultrasound
irradiation only 9-methyl-pyrido quinazolone derivative was obtained.
EXPERIMENTALPART
General Procedure
Synthesis of 11H-pyrido[2,1-b]quinazolin-11-one derivatives
using DMF as solvent.
A mixture of 2-chlorobenzoic acid derivative (6.26 g; 0.04 mol), anhy-
drous potassium carbonate (2.76 g; 0.02 mol), 2-aminopyridine derivative
(7.52 g; 0.08 mol), copper powder (0.2 g) in DMF (25 mL) was irradiated
for 20 min with a sonic horn at 20 kHz. The reaction mixture was slowly

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1780
Docampo Palacios and Pellon Comdom
added to water (100 mL), then left to stand overnight. The precipitate
11H-pyrido[2,1-b]quinazolin-11-one was purified by dissolving in the
corresponding solvent (see Table 3) and charcoal treatment. The Rf
values were obtained using a mixture of toluene:acetic acid (2:1).
Table 3. 11H-Pyrido[2,1-b]quinazolin-11-one derivatives synthesized and
analytical results.
Yield
(%)
M.p. (ꢀC)
(uncorrected)
M.p. (ꢀC)
Reported
No.
Substituent
Rf
1
2
3
4
5
6
7
8
9
R1¼R2¼R3¼R4¼R5¼H
R4¼CH3
75
82
69
79
65
67
78
89
63
211–212a
151–152b
90–92a
158–160b
190–191b
199c
257–258c
287–289c
207–209b
210[5,6]
152–153[5,7]
92–93[5]
157[5,6]
0.60
0.63
0.61
0.71
0.67
0.69
0.70
0.73
0.72
R5¼CH3
R1¼OCH3
R2¼Cl
190–192[5,6]
198[5]
R3¼NO2
R1¼NO2
258[5]
288–289[5]
208[5]
R1¼R3¼NO2
R2¼NO2
Calculated and experimental microanalysis
Calculated (%) Experimental (%)
No.
Formula
C
H
C
H
1
2
3
4
5
6
7
8
9
C12H8N2O
C13H10N2O
C13H10N2O
C13H10N2O2
C12H7ClN2O
C12H7N3O3
C12H7N3O3
C12H6N4O5
C12H7N3O3
73.47
74.28
74.28
69.03
62.47
59.75
59.75
50.35
59.75
4.08
4.76
4.76
4.42
3.04
2.90
2.90
2.10
2.90
73.40
74.53
74.36
68.90
62.61
59.55
59.88
50.49
59.63
4.23
5.11
4.88
4.25
3.19
2.84
2.67
1.91
2.63
c
aCrystallized from ethanol/water; bcrystallized from ethanol; crystallized from
dioxanel/water.

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Synthesis of 11H-Pyrido[2,1-b]quinazolin-11-one
1781
The yield, Rf value, melting point (uncorrected) and the elemental
analysis for each 11H-pyrido[2,1-b]quinazohn-11-one derivatives obtained
are reported in Table 3.
CONCLUSIONS
The use of ultrasound irradiation improved the synthesis of 11H-
pyrido[2,1b]quinazolin-11-one derivatives using DMF as solvent. A
number of pyridoquinazolone derivatives were prepared in good yield
in a very short reaction time.
REFERENCES
1. Pellon, R.; Carrasco, R.; Rodes, L. Synthesis of 11H-pyrido(2,1-b)-
quinazolin-11-one and derivatives. Synth. Comm. 1996, 26 (20),
3869–3876.
2. Abdel Aziz, M.A.; Daboun, H.A.; Abdel Gawad, S.M. a-Cyanothio-
acetamide and its derivatives in heterocyclic synthesis: preparation
of several new 4 oxoquinazoline derivatives. J. Prakt. Chem. 1990,
332 (5), 610–618.
3. Ensinger, H.; Birke, F.; Streller, I.; Schromm, K. Oxoquinazoline
derivatives as cell protectants. Ger. Offen. 3, 902, 639 (Cl.A61K31/
645), 02 Aug 1990, Appl 30 Jan 1989.
4. Matzkies, F.; Stechert, R.; Rauber, G.; Matzkies, F. Pilot study
on the effect of doqualast on dietary-induced hyperuncemia in
volunteers. Jr. Arzneim-Forsch. 1989, 39 (9), 1171–1172.
5. Fagundo, J.R.; Pellon, R.; Rosado, A.; Rodes, L. Mass espectrome-
try of the heterocycle 11H-pyrido(2,1-b)quinazolin-11-one and deri-
vatives. Revista CENIC Ciencias Quımicas 1983, 14 (l), 183–196; CA
101:170513r.
6. Rodrıguez, M.; Fernandez-Bertran, J.; Pellon, R., Rodes, L. NMR
spectra of 11H-pyrido(2,1-b)-quinazolin-11-one. Revista CEMC
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7. Biere, H.; Kaap, J.F. Pyrido[2,1-b]quinazolinone derivatives. Ger.
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Received in the USA August 16, 2002

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