The stereochemical consequences of N-N chiral axes in 3-acylaminoquinazolinones

• Main Author: Barker, Emma
• Published: University of Leicester 1995
• Subjects: 540
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.674362

The N,N-diacylation of 3-aminoquinazolinones results in the formation of imides. X-ray crystal structures of some of these compounds confirm the presence of N-N chiral axes. Both enantiopure diastereoisomers of one imide have been separated and each behaves as a chiral acylating agent. The faster eluted diastereoisomer reacts with methylbenzylamine with partial kinetic resolution to give a 3.6 : 1 ratio of diastereoisomers of the amide. The ability of 3-diacetylaminoquinazolinones to selectively acetylate one amine in the presence of another amine is also illustrated. Attempted aziridination of cyclic B-ketoesters, diketones and enol silyl ethers with 3-acetoxyamino-2-isopropyl-quinazolinone proceed in good yield with C-N bond cleavage of the intermediate aziridiue. The products from treatment of these (quinazolinon-3-yl)amino cyclic ketone derivatives with LTA are dependent on the solvent used. In methanol, ring-cleavage occurs for 5- and 6-membered rings to give imine-esters. In dichloromethane, 5-membered ring ketones undergo a ring-expansion reaction whereas when 6-membered ring analogues are used, no expansion occurs and the only product isolated is the benzoxazinone. A mechanism which accounts for this dependence on solvent is presented; radicals do not appear to be involved. The reaction of 3-aminoquinazolinones with ketones results in disparate ratios of C=N isomers of imines. The barriers to N-N bond rotation in some of these compounds have been calculated. The potential use of these imines for the preparation of enantiopure amines is examined. Addition of triethylamine (or other tertiary amines) to a solution of 3- acetoxyaminoquinazolinone, results in the formation of triethylammonium imdde. Solutions of this compound react with alkenes at -30° C to give aziridiaes; the reactivity of the aziridinating intermediate is consistent with its formulation as an azaimide (N-nitrene). Aziridination by the addition of 3-acetoxyaminoquinazolinones to alkenes in the presence of HMDS results in increased yields of aziridine products compared to those obtained in the absence of HMDS. The role of HMDS in these reactions is not clearly understood, although it seems likely that it is behaving in a similar way to trifluoroacetic acid which also brings about an enhancement of yields in these aziridinations.