STUDYING and WORKING

The Hydrolysis of Lactams Lactams are cyclic amides that have several features in common with their ester counterparts (lactones). As with lactones, the ring opening of lactams should be regarded as hydration rather than hydrolysis, since lactams, unlike amides and esters, yield only one product or metabolite. There are other similarities between lactams and lactones. Both lactam and lactone bonds become chemically more stable with increasing ring size, and five and six membered rings can, in both cases, be formed spontaneously from the appropriate precursor. The difference between these ring systems lies in their reactivity: lactams are generally less reactive than lactones, in the same sense that amides are more stable than esters. The differences in the mechanisms of hydrolytic cleavage of the amide and lactam bond will be discussed in this chapter. The greatest part of this text is devoted to the smallest lactam ring of significance in medicinal chemistry, namely the b -...