Experimental and computational studies of the regioselective protection of hydantoins using anhydride

The regioselective protection of alcohols, amines and a cage lactam with acetic anhydride was previously investigated. A six-membered cyclic transition state of acetic anhydride with the reagent was found. The same computational model was applied to three lactam systems, namely 5-methylhydantoin, 5,5-dimethyl-hydantoin and a pentacyclo-undecane cage hydantoin. The density functional hybrid method B3LYP was employed along with the 6-31+G(d) basis set to obtain the optimised geometries and corresponding energies of the different reagents, transition states and products. The computational model described herein correctly predicts the experimentally observed products. The synthesis and the NMR elucidation of three novel mono-Boc protected hydantoins are reported.