Peter Roschger

Synthesis and reactions of biginelli compounds −5. Facile preparation and resolution of a stable 5-dihydropyrimidinecarboxylic acid. ☆

Abstract The synthesis of enantiomerically pure 5-dihydropyrimidinecarboxylic acids 7a,b is described. Condensation of benzyl acetoacetate with methylurea and 2-naphthaldehyde gave Biginelli compound 3b, which after methylation and removal of the benzyl group led to racemic acid 5b. Fractional crystallization of diastereomeric α-methylbenzylammonium salts 6a,b followed by acidification provided the desired optically pure carboxylic acids 7a,b. Conversion of 7a,b to carboxylic acid azides 8a,b followed by Curtius rearrangement and reaction with 10-undecenol led to chiral urethanes 10a,b. The absolute stereochemistry of acids 7a,b was established by X-ray analysis of diastereomeric α-methylbenzylammonium-carboxylate 6c.

Malonates in Cyclocondensation Reactions

The use of malonates such as diethyl malonates 9, (chlorocarbonyl)ketenes 15 and bis(2,4,6-trichlorophenyl) malonates 18 as reagents for cyclocondensation with 1,3-dinucleophiles to give six-membered heterocycles is described. Further attempts to use malonates such as bis(trimethylsilyl) malonates 19 and bis(carbamimidoyl) malonates 29 as new cyclocondensation agents are described .

A simple and effective method for the reduction of acyl substituted heterocyclic 1,3-dicarbonyl compounds to alkyl derivatives by zinc - acetic acid - hydrochloric acid

3-Acyl-4-hydroxy-2(1H)-quinolones (1a–k) were reduced in good yields (66–97%) to 3-alkyl-4-hydroxy-2(1H)-quinolinones (2a–k) using zinc powder (particle size <45 μm) in acetic acid/hydrochloric acid. This method could be transformed to 3-acetyl-4-hydroxy-coumarin (1l), 3-acetyl-4-hydroxy-2-pyranone (3a) and 3-acetyl-4-hydroxy-2(1H)-pyridinone (3b), which yielded the 3-ethyl derivatives 2l, 4a and 4b, respectively.