Preparation of optically pure 3'-methylspiro[imidazolidine-4,4'(1'H)-quinazoline]-2,2',5(3'H)-trione by combination of optical resolution and racemization

Abstract

Optically pure 3'-methylspiro[imidazolidine-4,4'(l'/i)-qumazoline]-2,2',5(3/H)-trione was prepared by optical resolution using brucine as a resolving agent. The resulting optically pure spirohydantoin was racemized by refluxing in 1,2-dichlorobenzene for 17 h, or more effectively upon heating in 10% HC1 at 90 °C for 2 h. In the acid-catalyzed racemization, the introduction of difluoromethyl group at the 3-nitrogen of hydantoin ring increased the racemization rate, while the introduction of methyl group at the 3-nitrogen reduced it. These results suggest that the acid-catalyzed racemization proceeds via the N-acyliminium ion generated by the cleavage of the N3-C4 bond of the spirohydantoin ring.Several spirohydantoin derivatives which exhibit potent aldose reductase (AR) inhibitory activity are of potential value in the therapy of diabetic complications.1 We have previously reported the synthesis of a variety of spiro[imidazolidine-4,4/(TH)-quinazoline]-2,2',5(3,H)-triones by the reactions of isatin derivatives with either urea or isothiourea, followed by acid treatment.2,3 Of these, 3'methylspiro[imidazolidine-4,4'(l'fi)-quinazoline]-2,2/,5-

Cocrystal Formation between Chiral Compounds: How Cocrystals Differ from Salts

“…However, most of them do not correspond with the cocrystal definition stated above. After elimination of solvates, stochiometrically not well-defined structures, and/or structures with proton transfer between molecular partners, only 52 systems − ,− from the initial hit list were found relevant to this study.…”

“…Doing so, 8 out of the 52 systems were placed in the last caterogy, ,− as information in the literature is insufficient to classify this system into one of the two first categories. Astonishingly, 38 out of the remaining 44 systems − ,− belong to the first category of “enantiospecific systems”. A mere six systems ,− show formation of “diastereomeric systems”.…”

Synthesis, DFT calculations and cytotoxic investigation of platinum complexes with 3-thiolanespiro-5′-hydantoin and 4-thio-1H-tetrahydropyranespiro-5′-hydantoin

“…Many of the hydantoins containing natural and synthetic products exhibit diverse biological activities, such as antitumor [5], antiarrhythmic [6], anticonvulsant [7], herbicidal [8], and others [9][10][11]. Although hydantoin compounds are studied extensively, there are not many studies about their anticancer properties.…”

Reactions of some nitrogen heterocycles with chlorodifluoromethane under conditions of phase-transfer catalysis

“…In the case of indoles, the process was performed with sodium t-butoxide [8] or sodium hydride in DMF [9]; the former base was also applied for the reaction of carbostyril, giving mixture of N-and O-derivatives [8]. Similarly, quinoxalin-2-ones afforded mixtures of N-and O-difluoromethylated compounds in moderate yield when solid potassium carbonate or casium fluoride in DMF were applied [10], while the reaction of spiro[imidazolidine(quinazoline)]trione with sodium hydride in DMF led to formation only of the Nderivative [11].…”