Synthesis of some new pyridyl beta-lactam and thiazolidine derivatives

ABSTRACT

In search for new Beta-Lactam derivatives of modified antibiotic activity we have investigated the incorporation of pyridyl nucleus onto the Beta-Lactam moiety. Several pyridyl derivatives are known to exhibit interesting pharmacological properties as anti-inflammatory agents potentiators of adrenaline, ganglionic blockers, antiphlogistics, and postemergence agents on broad leaved plants. Thus 2-aminopyridine I was treated with aromatic aldehydes in absolute ethanol in presence of piperidine as a basic catalyst to afford Schiff bases II. Treatment of II with an acid chloride and tertiary amino would yield the desired Beta-lactam. The low yield of II in this case may be due to tautomerisation of 2-aminopyridine I/a to the mine form I/b. The presence of an electron withdrawing group would decrease such tautomerisation, and would facilitate condensation with aromatic aldehydes. Therefore nitration of 2-aminopyridine was carried out to afford a mixture of 3-and 5-nitro derivatives III and IV respectively. Interaction of IV and aromatic aldehydes afforded V[a] [R=H] in 37 percent yield. Higher yield was obtained when IV was allowed to react with 4-nitrobenzaldehyde. Treatment of V with chloroacetyl chloride and triethylamine afforded the corresponding Beta-lactam VI[6. The IR spectra of compounds VI showed a well definite absorption band at 1760-1720 cm[-1] [the C=O stretching of monocyclic Beta-latam]. The cycloaddition reactions of thioglycolic acid with the azomethine group in V was also investigated using a water separator system for about five days giving of the cyclic 4-thiazolidinone compounds VII but in low yields. The IR spectra of VII showed a definite absorption band at 1680 -1645 cm[-1] [C=O group]