Lactams seven-membered, hydrolysis

Caprolactam (5.68, Fig. 5.21) has a seven-membered lactam ring and is a major industrial compound in the production of Nylon , its polymer. This compound shows only moderate levels of toxicity in mice and rats when administered orally. The hydrolysis product 6-aminohexanoic acid (5.69) was a minor metabolite in rats [176]. Hydroxylation in the y-position to yield 5.70 without preliminary hydrolysis of the lactam linkage has been shown to be the major metabolic pathway. This metabolite hydrolyzes in urine to produce 6-amino-4-hydroxyhexanoic acid (5.71), which is in equilibrium with the corresponding lactone (5.72). 

Hydrolytic cleavage of a seven-membered ring occurs in the metabolism of chlordiazepoxide (5.82, Fig. 5.22,a) and other benzodiazepines (see also Sect. 11.9). The lactam ring opened metabolite 5.83 was detected in humans and dogs and is believed to be generated by hydrolysis of the intermediate lactam [181][182], However, the diazepine ring can be split by other mech-... 

Spectroscopic evidence of the seven-membered rings has been found in the preparation of polyimides from pyromellitic dianhydride and methylenediphenyl-diisocyanate (MDI) [105]. The reaction is conducted in solution of aprotic solvents, with reagents addition at low temperature and a maximum reaction temperature of about 130 °C. On the other hand, polyimides of very high molecular weight have not been reported by this method. The mechanism is different when the reaction is accelerated by the action of catalysts. Catalytic quantities of water or alcohols facilitate imide formation, and intermediate ureas and carbamates seem to be formed, which then react with anhydrides to yield polyimides [106]. Water as catalyst has been used to exemplify the mechanism of reaction of phthalic anhydride and phenyl isocyanates, with the conclusion that the addition of water, until a molecular equivalent, markedly increases the formation of phthalimide [107] (Scheme 13). The first step is actually the hydrolysis of the isocyanates, and it has been claimed that ureas are present in high concentration during the intermediate steps of the reaction [107]. Other conventional catalysts have been widely used to accelerate this reaction. Thus, tertiary amines, alkali metal alcoholates, metal lactames, and even mercury organic salts have been attempted [108]. 

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