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Synlett 2004(2): 0283-0286  
DOI: 10.1055/s-2003-43367
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Novel Microwave-assisted One-pot Synthesis of Pyrano[2,3-d]pyrimidines and Pyrido[2,3-d]pyrimidines via a Three Component Reaction in Solvent-Free Condition

Ipsita Devi, Pulak J. Bhuyan*
Medicinal Chemistry Division, Regional Research Laboratory, Jorhat.785006, Assam, India
Fax: +91(376)2370011; e-Mail: pulak_jyoti@yahoo.com;
Further Information

Publication History

Received 15 September 2003
Publication Date:
18 December 2003 (online)

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Abstract

Three-component cyclocondensation of barbituric acids 1, triethylorthoformate 2 and alkyl nitriles 3 in presence of acetic anhydride proceeds under microwave-assisted conditions to give pyrano[2,3-d]pyrimidines 4 in excellent yields. 6-Aminouracils 5 or 6-hydroxy-aminouracils 7 react with 2 and 3 under identical conditions to yield pyrido[2,3-d]pyrimidines 6 or pyrido[2,3-d]pyrimidine oxides 8 in high yields.

Key words

solvent-free reaction - multicomponent reaction - ­microwave-assisted reaction - pyrano[2,3-d]pyrimidines - pyrido[2,3-d]pyrimidines

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In a typical experimental procedure equimolar amounts of 1a (0.312 g, 2 mmol), triethylorthoformate 2 (0.296 g, 2 mmol), malononitrile 3a (0.132 g, 2 mmol) and acetic anhydride (0.648 g, 6 mmol) were added to the reaction vessel of the microwave reactor (Synthewave 402 Monomode Reactor from Prolabo) and allowed to react under microwave irradiation at 360 W and 75 °C for 5 min. The mixture was cooled to r.t. and the solid compound obtained was recrystallised from EtOH (0.392 g, 85%). The compound was confirmed as 4a from the spectroscopic data and elemental analysis. Mp 215 °C. 1H NMR (300 MHz, CDCl3): δ = 3.00 (s, 3 H), 3.15 (s, 3 H), 8.10 (s, 1 H), 8.85 (s, 1 H). 13C NMR (300 MHz, CDCl3): δ = 28.3 (3-Me), 36.6 (1-Me), 106.4 (C-4a), 118.8 (CN), 142.6 (C-7), 145.02 (C-6), 147.75 (C-5), 151.2 (C-2), 154.12 (C-8a), 158.0 (C-4). IR: 2217, 1695, 1650 cm-1. MS: 232 [M+]. Anal. Calcd for C10H8N4O3: C, 51.72; H, 3.44; N, 24.13. Found: C, 51.75; H, 3.40; N, 24.15. Similarly compounds 4b-d, were synthesised (Table [1] ) and characterised.

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In a simple experimental procedure equimolar amounts of 5a (0.340 g, 2 mmol), triethylorthoformate 2 (0.296 g, 2 mmol), malononitrile 3a (0.132 g, 2 mmol) and acetic anhydride (0.648 g, 6 mmol) were allowed to react under microwave irradiation at 360 W and 75 °C for 2 min in a monomode microwave reactor. The mixture was cooled to r.t. and the solid compound obtained was recrystallised from EtOH (0.438g, 95%). The compound was confirmed as 6a from the spectroscopic data and elemental analysis. Mp 350-352 °C (lit. 352-353 °C). 1H NMR (300 MHz, CDCl3): δ = 3.00 (s, 3 H), 3.15 (s, 3 H), 7.75 (br s, 2 H), 8.40 (s, 1 H). IR: 3250, 2213, 1690, 1655 cm-1 . MS: 231 [M+]. Anal. Calcd for C10H9N5O2: C, 51.94; H, 3.89; N, 30.30. Found: C, 52.00; H, 3.95; N, 30.25. Similarly compounds 6b-d were synthesised (Table [1] ) and characterised.

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In a typical experimental procedure equimolar amounts of 7a (0.342 g, 2 mmol), triethylorthoformate 2 (0.296 g, 2 mmol), malononitrile 3a (0.132 g, 2 mmol) and acetic anhydride (0.648 g, 6 mmol) were allowed to react under microwave irradiation at 360 W and 75 °C for 8 min in a monomode microwave reactor. The mixture was cooled to r.t. and the solid compound obtained was recrystallised from EtOH (0.321 g, 65%). The compound was confirmed as 8a from the spectroscopic data and elemental analysis. Mp 218 °C (lit. 218 °C). 1H NMR (300 MHz, CDCl3): δ = 3.00 (s, 3 H), 3.15 (s, 3 H), 7.85 (br s, 2 H), 8.15 (s, 1 H). 1 3C NMR (300 MHz, CDCl3): δ = 28.5 (3-Me), 36.8 (1-Me), 107.25 (C-4a), 118.75 (CN), 143.5 (C-7), 145.5 (C-6), 146.55 (C-5), 151.25 (C-2), 154.25 (C-8a), 158.0 (C-4). IR: 3255, 2216, 1715, 1642, 1625 cm-1. MS: 247 [M+]. Anal. Calcd for C10H9N5O3: C, 48.58, H, 3.64, N, 28.34. Found: C, 48.50, H, 3.70, N, 28.40. Similarly compounds 8b-d were synthesised (Table [1] ) and characterised.