Understanding Chemistry and Unique NMR Characters of Novel Amide and Ester Leflunomide Analogues

Abstract

A series of diverse substituted 5-methyl-isoxazole-4-carboxylic acid amides, imide and esters in which the benzene ring is mono or disubstituted was prepared. Spectroscopic and conformational examination was investigated and a new insight involving steric interference and interesting downfield deviation due to additional diamagnetic anisotropic effect of the amidic carbonyl group and the methine protons in 2,6-diisopropyl-aryl derivative (2) as conformationaly restricted analogues Leflunomide was discussed. Individual substituent electronic effects through π resonance of p-substituents and most stable conformation of compound (2) are discussed.

Keywords

• leflunomide derivatives
• 2,6-diisopropylphenyl anilide chemical shift abnormalities
• 5-methyl-4-isoxazole derivatives