Synthesis of Novel 3-chloro-3-(4-oxo-4H-pyrido[1,2-a]pyrimidin-3yl)acrylaldehydes and their Subsequent Knoevenagel Condensation with Various Active Methylene Compounds

Author(s): P. Venkateshwarlu, P.K. Dubey*

Journal Name: Letters in Organic Chemistry

Volume 14 , Issue 5 , 2017


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Abstract:

Background: Simple and efficient method has been developed for the Knoevenagel condensation of novel 3-chloro-3-(4-oxo-4H-pyrido[1,2-a]pyrimidin-3yl)acrylaldehyde (5) with active methylene compounds such as malononitrile (6), 3-methyl-1-phenyl-pyrazole-5(4H)-one (7), 3-methyl-1Hpyrazole- 5(4H)-one (8), Meldrum’s acid (9), Barbituric acid (10) and 4-hydroxycoumarin (11) by stirring in ethanol at room temperature for 2 h in the presence of L-proline as a catalyst yielding the products 12a, b to 17a, b respectively.

Methods: In this article, we reported a new synthesis of 3-chloro-3-(4-oxo-4H-pyrido[1,2-a]pyrimidin- 3yl)acrylaldehyde (5) which was prepared from the 2-aminopyridine 1 condensed with ethyl ethoxymethyleneacetoacetate (2) in ethanol under refluxing conditions for 4 h giving a product which has been characterized as ethyl 3-oxo-2-((pyridin-2-ylamino)methylene)butanoate 3 on the basis of its spectral data. On thermal cyclization, in diphenyl ether for 30 min at 255oC, 3a gave a product 4. Vilsmeier-Haack formylation of 4 at RT for 4 h gave a product 5. Condensation of 5 with malononitrile, 3-methyl-1-phenyl-pyrazole-5(4H)-one, 3-methyl-1H-pyrazole-5(4H)-one, Meldrum’s acid, Barbituric acid and 4-hydroxycoumarin (11) by stirring in ethanol at room temperature for 2 h in the presence of L-proline as a catalyst yielding the products 12a, b to 17a, b respectively.

Result: A novel preparation of 3-chloro-3-(4-oxo-4H-pyrido[1,2-a]pyrimidin-3yl)acrylaldehyde (5) method is reported in this article, along with the condensation of 5 with various active methylene compounds by stirring in ethanol at room temperature for 2 h in the presence of L-proline as a catalyst yielding the products 12a, b to 17a, b respectively. The structures of the synthesized compounds were confirmed by 1H-NMR, 13C-NMR, GC-MS and IR spectral data. All of the intermediates were structurally characterized IR (KBr): 1747 and 1697 cm-1 (strong, sharp of absorptions due to the -CHO and -N-CO-). 1H-NMR (DMSO-d6/TMS): δ 7.4-7.8 (t, 3H, Ar-H), 8.7 (s, 1H, α-H to the enamine nitrogen), 9.2 (q, pyridine ring proton), 10.2 (s, 1H, -CHO). LC-MS (HR-MS): m/z 235.0271, [(C12H14N2O3) +H]+.

Conclusion: In conclusion, L-proline has been employed as an efficient catalyst for the preparation of a simple, efficient method for the synthesis of condensed compounds and a novel synthetic route to 3- chloro-3-(4-oxo-4H-pyrido[1, 2-a]pyrimidin-3yl)acrylaldehyde(5), whose condensation with active methylene compounds (6-11) reactions at RT, led to products 12-17.

Keywords: Active methylene compounds, Knoevenagel condensation, L-proline, Pyridopyrimidines, Vilsemeier-Haack formylation.

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Article Details

VOLUME: 14
ISSUE: 5
Year: 2017
Published on: 13 June, 2017
Page: [324 - 329]
Pages: 6
DOI: 10.2174/1570178614666170310122550
Price: $65

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