888 J. Chin. Chem. Soc., Vol. 50, No. 4, 2003
Abdel-Razik
prominent nitrile absorption at 2215 cm-1, therefore ruling
out cyclization with the nitrile.
(0.01 mole) 2 in methylene chloride (50 mL) containing three
drops of triethylamine at 0 °C was added Chlorocarbonyl
isocyanate 1 (0.01 mole). The reaction mixture was stirred
for 1 h at room temperature. The solution was left to stand
overnight at room temperature. The solid was collected by
filtration and crystallized from ethanol.
3: 2.21 g (89%); m.p. > 300; IR (KBr) nmax/cm-1: 1720
(CO), 2215 (CN), 3350 (NH); 1H NMR (200 MHz, DMSO-
d6) d/ppm: 8.3 (br, s, H, NH) D2O exchangeable, 1.2 (t, 3H, J
= 8, CH3), 4.3 (q, 2H, J = 6, CH2); MS m/z: 249 (M+, 77%).
Anal. Calcd. for C10H7N3O5 (Mr = 249.1813): C, 48.20;
H, 2.83; N, 16.86%, found: C, 48.14; H, 2.77; N, 16.78%.
The behaviour of compound 3 towards N-nucleophiles
4a-f was studied. Thus, compound 3 reacted with hydroxyl-
amine hydrochloride 4a in boiling pyridine affording 2-
substituted pyrido[4,3-d]pyrimidine derivative 5 through
hetero ring opening followed by ring closure (intermediate
B).
Similarly, compound 3 reacted with formamide 4b re-
sulted in the ring transformation to afford pyrido[4,3-d]pyr-
imidine derivative 6. Compound 3 reacted with semicar-
bazide 4c in boiling pyridine affording 2-substituted pyrido-
[4,3-d]pyrimidine 7 which on reaction with diethylmalonate
4g resulted in the formation of 2,4,6-trioxopyrimidinyl-
[1¢:2]pyrido[4,3-d]pyrimidine derevative 11. While on reac-
tion of 3 with hydrazine hydrate afforded 2-amino pyrido-
[4,3-d]pyrimidine 8 which reacted with benzaldehyde 4h in
ethanol to afford compound 12 which in its turn cyclized with
thioglycolic acid 4i resulted in the formation of 2-thiazolo-
[3¢:2]pyrido[4,3-d]pyrimidine derivative 13.
Preparation of 2-substituted-2,3,5,8-tetraoxo-7-cyano-
pyrido[4,3-d]pyrimidine 5-8, pyrimidino[i]1,5a-diaza-9-
oxafluorene 9 and pyrimido[i]5a-aza-9-thiafluorene 10;
general procedures
A mixture of 3 (0.01 mole) and N-nucleophile 4a-f
(0.01 mole) was refluxed in (pyridine for 5-7, ethanol for 8,
freshly fused sodium acetate 0.49 g in glacial acetic acid 40
mL for 9, 10) for 3 h. the reaction mixture was cooled and the
solid product was collected by filtration and crystallized from
ethanol.
5: 1.959 g (83%); m.p. 320; IR (KBr) nmax/cm-1: 1725
(CO), 2215 (CN), 3350 (NH); 1H NMR (200 MHz, DMSO-
d6) d/ppm: 8.3 (br, s, H, NH) D2O exchangeable, 6.7 (s, 1H,
OH), 9.2 (s, 1H, 8a-H); MS m/z: 236 (M+, 44%).
Anal. Calc. for C8H4N4O5 (Mr =236.1426): C, 40.69; H,
1.70; N, 23.72%, found: C, 40.61; H, 1.63; N, 23.65%.
6: 1.69 g (77%); m.p > 300; IR (KBr) nmax/cm-1: 1725
(CO), 2215 (CN), 3350 (NH); 1H NMR (200 MHz, DMSO-
d6) d/ppm: 8.3 (br, s, H, NH), 9.2 (s, 1H, 8a-H); MS m/z: 220
(M+, 38%).
Compound 3 reacted with 2-hydroxy 3-amino pyridine
4e in the presence of sodium acetate and glacial acetic acid to
afford pyrimido[i]1,5a-diaza-9-oxafluorene derivative 9
through ring opening and ring closure followed by elimina-
tion of water (intermediate C).
Similarly, compound 3 reacted with 0-aminothiophe-
nole 4f to afford pyrimido[i]5a-aza-9-thiafluorene derivative
10. The prepared compounds are in agreement with their
spectral data (Scheme II, cf experimental).
On the other hand compound 3 was subjected to react
with active methylene reagents 4j to yield pyrimidine deriva-
tives 14-16 in their enolic form without further cyclization
under the reaction conditions which cyclized when refluxed
in ethanol/benzene containing sodium ethoxide 4k to afford
1,5,7-triaza-10 oxaphenanthrene derivatives 17-19. The IR
spectrum of the cyclization products 17, 18 proved the ab-
sence of nitrile absorption, therefore, ruling in cyclization
Anal. Calc. for C8H4N4O4 (Mr = 220.1436): C, 43.64; H,
1.83; N, 25.45%, found: C, 43.56; H, 1.85; N, 25.38%.
7: 2.19 g (79%); m.p. 315; IR (KBr) nmax/cm-1: 1728
1
(CO), 2215 (CN), 3350 (NH), 3245 (NH2); H NMR (200
1
with nitrile. The H NMR spectra of cyclization products
MHz, DMSO-d6) d/ppm: 8.3 (br, s, H, NH), 9.2 (s, 1H, 8a-H),
6.3 (s, 2H, NH2); MS m/z: 278 (M+, 47%).
17-19 revealed an enol hydrogen at 13.63 ppm as a broad sig-
nal (Scheme III, cf experimental). The purity of the prepared
compounds were measured using thin layer chromatography
TLC.
Anal. Calc. for C9H6N6O5 (Mr = 278.1834): C, 38.85; H,
2.17; N, 30.21%, found: C, 38.78; H, 2.09; N, 30.14%.
8: 1.78 g (76%); m.p. > 300; IR (KBr) nmax/cm-1: 1725
1
(CO), 2215 (CN), 3240 (NH2), 3350 (NH); H NMR (200
MHz, DMSO-d6) d/ppm: 8.3 (br, s, H, NH), 5.4 (s, 2H, NH2),
9.2 (s, 1H, 8a-H); MS m/z: 235 (M+, 22%).
EXPERIMENTAL
Anal. Calc. for C8H5N5O4 (Mr = 235.1585): C, 40.86; H,
2.14; N, 29.78%, found: C, 40.81; H, 2.07; N, 29.69%.
9: 2.15 g (73%); m.p. 276; IR (KBr) nmax/cm-1: 1720
(CO), 2215 (CN), 3350 (NH), 1H NMR (200 MHz, DMSO-
Preparation of 1-ethoxy-4-cyano-3,6,8-trioxopyrano-
[4,3-d]pyrimidine 3
To a stirred solution of the dimer of ethylcyanoacetate