Assisted hydrolysis of cis-2-(3-phenylthioureido)cyclopentane-carbonitrile in alkaline solution.Solvent dependent switch from hydrolysis to rearrangement of the iminothiooxopyrimidine intermediate

摘要

The cis and trans isomers of 2-(3-phenylthioureido)cyclopentanecarbonitrile, 1, and the respective carboxamides, 3, and acids, 4, have been prepared. Acid cyclization of both nitriles, faster with the cis isomer, gave the more stable cis-2-thiooxo-cyclopenta[d]pyrimidin-4-one, 7. In base cis-1 formed the cis 4-imino-2-thiooxopyrimidine 2 which in aqueous alkali broke down via 3 to the acid 4; while in the presence of 66% acetonitrile 2 rearranged to the 4-phenyliminopyrimidine 5 to give as final product the thioureido acid 6 calTying no phenyl group. The tH NMR data for imino and phenylimino derivatives 2 and 5 showed strong bias for conformation A with 1-N pseudoaxial in the cvclopentane ring. Spectra of the E and Z isomers of the iminopyrimidine 2 under slow exchange could be recorded in DMSO-d_6. The phenylimino tautomer of 5 is observed in CD_3OD and in CDCl_3 with the E and Z isomers in a 1:1 ratio. In DMSO-d_6 the phenylamino tautomer Sn is also detected. The first process in aqueous KOH, the conversion of nitrile cis-1 into the imino intermediate 2, reaches an equilibrium which shifts towards the nitrile at higher alkalinities because of ionization of the phenyithioureido group (K_e = [2]/[1I = 2.43 and pKAH = 12.74). The cyclization of 1 to 2 is first order in [OH-I while the slower breakdown of 2 is pH independent. The latter is iO~ times faster than the hydrolysis of acetonitrile evidencing substantial anchimeric assistance. The change in the reaction route towards the rearranged phenxliminopvrimidine 5 upon addition of acetonitrile can be caused by the lower dielectric constant favouring the elimination step leading to the intermediate isothiocyanate, and by increased activity of OH~- accelerating the (presumablv second order elimination step as opposed to the pH-independent hydrolysis of the imino derivative 2.