Synthesis of derivatives of 7,8-dihydrothiazolo[2,3-i]purine by halocyclization of 6-allylthiopurine

Article abstract of DOI:10.1007/s10593-005-0077-8

7-Halomethyl-7,8-dihydrothiazolo[2,3-i]purines were synthesized by the reaction of bromine and iodine with 6-allylthiopurine.

Full text of DOI:10.1007/s10593-005-0077-8

Chemistry of Heterocyclic Compounds, Vol. 40, No. 11, 2004
A CONVENIENT ONE-POT SYNTHESIS
OF BENZOPYRIMIDO[1,8]NAPHTHYRIDINES
BY KNOEVENAGEL CONDENSATION
R. Nandha Kumar, T. Suresh, and P. S. Mohan
A
series of 1-oxo-2,4-diphenyl-3-thioxobenzo[g]pyrimido[6,5-b]-1,8-naphthyridines has been
synthesized by Knoevenagel condensation from 3-formyl-2-oxoquinolines and N,N-diphenyl-2-
thiobarbituric acid on refluxing with liquid ammonia in absolute ethanol.
Keywords:
benzopyrimidonaphthyridines,
N,N-diphenyl-2-thiobarbituric
acid,
3-formyl-2-
oxoquinoline, Knoevenagel condensation.
2
-Aminonicotinaldehyde was used as a potential starting material for the synthesis of 1,8-naphthyridines
via Friedlander condensation [1-3]. In the present work an alternative route for the synthesis of
,8-naphthyridines from 3-formyl-2-oxoquinoline in a one-pot method by Knoevenagel condensation [4-7] is
1
discussed. Quinoline derivatives [8-11], quinoline amines [12-15], and 1,8-naphthyridines [16-20] are
pharmacologically important. So, these moieties attract considerable attention as active biocidal agents and
prompted us to synthesize a series of 1,8-naphthyridines.
O
R3
R2
R3
CHO
Cl
CHO
O
4
N HCl
N
+
O
R2
N
N
H
N
S
R1
R1
2
1
a–f
O
N
R3
N
Liq. NH , dry EtOH
3
reflux, 5 h
R2
N
N
S
R1
3
a–f
1
2
3
1
2
3
1
3
2
1
, 3 a R = R = R = H; b R = Me, R = R = H; c R = R = H, R = Me;
1
2
3
1
2
3
1
2
3
d R = R = H, R = Me; e R = OMe, R = R = H; f R = R = H, R = OMe
_
_________________________________________________________________________________________
Departament of Chemistry, Bharathiar University, Coimbatore-641046, TamilNadu, India; e-mail:
ps_mohan_in@yahoo.com. Published in Khimiya Geterotsiklicheskikh Soedinenii, No. 11, 1723-1725,
November, 2004. Original article submitted September 2, 2002.
1
490
0009-3122/04/4011-1490©2004 Springer Science+Business Media, Inc.

3
-Formyl-2-oxoquinoline 1 [21, 22], N,N-diphenyl-2-thiobarbituric acid (2) [23, 24], and liquid
ammonia were refluxed in absolute ethanol for 5 h to give the product (74% yield), whose IR spectrum showed
-
1
-1
-1
strong absorption bands at 1325 cm due to the C=S group, 1680 cm for the C=O group, and 1620 cm and
1
-
1
1
595 cm for the C=N groups. Its H NMR and mass spectra as well as data of elemental analysis corroborated
with the structure of 1-oxo-2,4-diphenyl-3-thioxobenzo[g]pyrimido[6,5-b]-1,8-naphthyridine (3a). Other
compounds 3 were obtained similarly (Table 1).
In conclusion, the reaction proceeds smoothly through the Knoevenagel condensation between the
formyl moiety and the active methylene group of N,N-diphenyl-2-thiobarbituric acid to give after elimination of
a water molecule the desired substituted 1-oxo-3-thioxobenzo[g]pyrimido[6,5-b]-1,8-naphthyridines.
EXPERIMENTAL
Thin layer chromatography was used to access the reaction course and the purity of products. Melting
points were determined on a Boetius Microheating Table and Mettler-FP5 Melting apparatus and are
uncorrected. IR spectra were recorded in a Shimadzu-8201FT instrument in KBr discs and only significant
1
absorption levels (reciprocal centimeter) are listed. H NMR spectra were recorded in an AMX-400 MHz
spectrometer in CDCl solution; chemical shifts are expressed in ppm (δ) relative to TMS. Mass spectra were
3
recorded on a Jeol-D-300 mass spectrometer. CHN analyses were carried out on Carlo Erba 106 and Perkin–
Elmer Model 240 analyzers.
TABLE 1. Characteristics of Synthesized Compounds 3a-f
Empirical
formula
Found, %
Calculated, %
H
1
Com-
pound
——————
mp, IR spectrum, H NMR spectrum, Yield,
-1
ν, cm
δ, ppm
%
°C
(Mol. Wt.)
C
N
3
3
a
C
(
26
H
16
N
4
OS 72.02 3.64
2.21 3.73
432.46)
12.87
12.96
280 1680, 1620, 8.1 (1H, s, C11-H);
1595, 1325 8.4 (1H, s, C12-H);
74
7
6
.8-7.9 (14H, m,
Ar–H)
b
C
27
H
18
N
4
OS 72.71 4.13
2.63 4.06
12.48
12.55
183 1690, 1635, 2.3 (3H, s, CH
3
);
82
68
79
73
80
7
(446.49)
1585, 1330 8.0 (1H, s, C11-H);
8
7
.5 (1H, s, C12-H);
.1-7.8 (13H, m,
Ar–H)
3
3
3
3
c
d
e
f
C
27
H
18
N
4
OS 72.52 4.01
2.63 4.06
12.46
12.55
240
3
1685, 623, 2.5 (3H, s, CH );
7
(446.49)
1580, 1320 8.1 (1H, s, C11-H);
8
7
.7 (1H, s, C12-H);
.0-8.0 (13H, m,
Ar–H)
215 1670, 1610, 2.4 (3H, s, CH
1590, 1323 8.2 (1H, s, C11-H);
C
(
27
H
18
N
4
OS 72.60 3.98
2.63 4.06
446.49)
12.59
12.55
3
);
7
8
7
.6 (1H, s, C12-H);
.0-7.9 (13H, m,
Ar–H)
C
27
H
18
N
4
2
O S
70.02 3.80
0.12 3.92
12.17
12.12
3
174 1668, 1605, 3.9 (3H, s, OCH );
7
(462.49)
1587, 1328 8.3 (1H, s, C11-H);
8
7
.5 (1H, s, C12-H);
.1-8.1 (13H, m,
Ar–H)
C
27
H
18
N
4
2
O S
70.16 3.86
0.12 3.92
12.08
12.12
3
195 1660, 1615, 3.9 (3H, s, OCH );
7
1
593, 1322 8.2 (1H, s, C11-H);
(462.49)
8
.6 (1H, s, C12-H);
6
.9-8.0 (13H, m,
Ar–H)
1
491

Synthesis of Benzopyrimido[1,8]naphthyridines. 3-Formyl-2-oxoquinoline 1a-f (1 mmol) and
N,N-diphenyl-2-thiobarbituric acid (2) (1 mmol) were dissolved in anhydrous ethanol with 2 ml of liquid
ammonia and refluxed on a water-bath for about 5 h. After the completion of the reaction, inferred through TLC
studies, the volume was reduced to half. The separated product was collected and recrystallized with
chloroform–methanol. A series of compounds 3a-f was synthesized and their characteristic data are presented in
Table 1.
The authors thank CSIR, New Delhi for the award of Senior Research Fellowship (R.N.K.) and
Bharathiar University for the award of University Research Fellowship (T.S.). SIF, Indian Institute of Science,
Bangalore and Central Drug and Research Institute, Lucknow supported the spectral details.
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