Acid Amides, Lactams, and Imides

With succinamide, the major products were pyrrolidine and A-substituted pyrrolidine, which might be formed through the reaction paths shown in eq. 10.36.76 Under similar conditions, the hydrogenation of glutaramide gave piperidine in high yield (eq. 

Over nickel catalysts, phthalimide (eq. 10.48),80 and IV-substituted succinimides and glutarimides are hydrogenated to give the lactams at 200-220°C.77 Hydrogenations were rather slow at these temperatures, but use of dioxane for Raney Ni at temperatures above 220°C should be avoided.81 The reaction with /V-pcntylsuccinimide (eq. 10.49) was incomplete even after two applications of catalyst. The low yield of the pyrrolidone probably resulted from the difficulty of separating the pyrrolidone from the imide. 

In cases of /V-p-phenethylimides, the first reaction was saturation of the benzene ring, which occurred rapidly at 200°C. When the hydrogenation was interrupted after 20 min, /V-(2-cyclohexylethyl)succinimidc could be isolated in a yield of 93%, and it was hydrogenated to give the corresponding pyrrolidone in 79% yield (eq. 10.50). 

Similarly, hydrogenation of (V-phenethyl-P-methylglutarimide gave the corresponding (V-cyclohexylethylpiperidone in 74% yield. In one patent, 3,4,5,6-tetrahydro-phthalimide was successfully hydrogenated to give octahydroisoindole in 65% yield over Raney Ni in cyclohexane at 250°C and 14.7 MPa H2.82 

McAlees and McCrindle found that phthalimides with electron-withdrawing substituents such as an acyl or alkoxycarbonyl on the imide nitrogen were hydrogenated to the corresponding 3-hydroxyisoindolin-l-ones over 10% Pd-C in ethyl acetate or ethanol (eq. 10.51).83 

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