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

The cis and trans isomers of 2-(3-phenylthioureido)cyclopentanecarbonitrile 1, and the respective carboxamides, 3, and acids, 4, have been prepared. A cid 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 v ia 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 ac id 6 carrying no phenyl group. The H-1 NMR data for imino and phenylimino d erivatives 2 and 5 showed strong bias for conformation A with 1-N pseudoaxi al in the cyclopentane ring. Spectra of the E and Z isomers of the iminopyr imidine 2 under slow exchange could be recorded in DMSO-d(6). The phenylimi no tautomer of 5 is observed in CD3OD and in CDCl3 with the E and 2 isomers in a 1:1 ratio. In DMSO-d(6) the phenylamino tautomer 5a is also detected. The first process in aqueous KOH, the conversion of nitrile cis-l into the imino intermediate 2, reaches an equilibrium which shifts towards the nitr ile at higher alkalinities because or. ionization of the phenylthioureido g roup (K-e = [2]/[1] = 2.43 and pK(AH) = 12.74). The cyclization of 1 to 2 i s first order in [OH-] while the slower breakdown of 2 is pH independent. T he latter is 10(4) times faster than the hydrolysis of acetonitrile evidenc ing substantial anchimeric assistance. The change in the reaction route tow ards the rearranged phenyliminopyrimidine 5 upon addition of acetonitrile c an be caused by the lower dielectric constant favouring the elimination ste p leading to the intermediate isothiocyanate, and by increased activity of OH- accelerating the (presumably) second order elimination step as opposed to the pH-independent hydrolysis of the imino derivative 2.