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Nitrogen bridgehead compounds. Part 50 . Vilsmeier‐haack acylation of 6,7,8,9‐tetrahydro‐4 H ‐pyrido[1,2‐ a ]pyrimidin‐4‐ones, Part 5
Author(s) -
Horváth Ágnes,
Hermecz István,
Podányi Benjamin,
Mészáros Zoltán
Publication year - 1985
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570220302
Subject(s) - iminium , chemistry , formamide , triethyl orthoformate , acylation , substituent , medicinal chemistry , chloride , aniline , benzoyl chloride , stereochemistry , nuclear magnetic resonance spectroscopy , organic chemistry , catalysis
6‐Methyl‐6,7,8,9‐tetrahydro‐4 H ‐pyrido[1,2‐ a ]pyrimidin‐4‐ones 1‐5 were subjected to Vilsmeier‐Haack acylation with complexes of phosphoryl chloride and different amides. Acylation at position 9 of the pyridopyrim‐idines was successful with the iminium salt formed in situ from N ‐formylpiperidine, N ‐methylformanilide or N,N ‐diethylbenzamide, but unsuccessful with the iminium salt formed from N,N ‐diethylacetamide or N,N ‐di‐ethylisobutyramide, respectively. The iminium salt formed from formanilide, N ‐methylpyrrolidinone or formamide reacted only with those tetrahydropyridopyrimidinones which contain a strongly electronegative substituent ( e.g. CN or CO 2 Et) in position 3. With the latter derivatives, the 9‐phenylaminomethylene group could be introduced using N,N ‐diphenylformamide or in a “one‐pot” procedure with aniline and triethyl orthoformate. Ethanolysis of 9‐ N ‐methyl‐ N ‐phenylaminomethylene derivatives 15 and 19 afforded 9‐ethoxy‐methylene compounds 26 and 27 in the presence of hydrogen chloride. The structures of the 9‐substituted 6‐methyltetrahydropyridopyrimidin‐4‐ones 14‐25 were elucidated by means of uv, 1 H and 13 C nmr spectroscopy. 9‐Piperidinomethylene 14 , 9‐( N ‐methyl‐ N ‐phenylaminomethylene 15‐19 and 9‐( N ‐methyl‐2‐pyrrolidinylidene) 21 derivatives exist as E geometric isomers. 9‐Phenylaminomethylene‐6‐methyl‐4‐oxo‐6,7,8,9‐tetra‐hydro‐4 H ‐pyrido[1,2‐ a ]pyrimidine‐3‐carbonitrile 20 displays a solvent‐dependent E‐Z isomerism. The bis‐compound 25 contains both E and Z geometric exo C CH double bonds. 9‐Benzoyl derivatives 23 and 24 exist predominantly as the 1,6,7,8‐tetrahydropyridopyrimidin‐4‐one tautomer.