Cyclization Path Research Articles

ChemInform Abstract: SYNTHESIS OF AZAPOLYCYCLIC COMPOUNDS BY THE AMINIUM RADICAL ROUTE: REARRANGEMENTS OF C‐NITROSO COMPOUNDS AND THEIR STEREOELECTRONIC REQUIREMENTS

AbstractNach Literatur wurde Allylbromid mit Cyclopentadien zum 2‐endo‐Brommethyl‐bicyclohepten umgesetzt (Gesamtausb 70.5%, mit etwa 30% exo‐Isomerem), das mit Methylamin, danach mit Distickstofftetroxid zum Nitrosamin (I) umgesetzt wurde.

Synthesis of azapolycyclic compounds by the aminium radical route: rearrangements of C-nitroso compounds and their stereoelectronic requirements

The aminium radicals generated from the photolysis of N-nitroso-endo-2-methylamino-methylbicyclo[2.2.1]hept-5-en and N-nitroso-endo-2-methylaminomethylbicyclo[2.2.2]oct-5-ene cyclize at the C-6 position, since the relevant reacting centers can achieve excellent orbital overlap with minimum molecular motion in comparison to the alternative cyclization path at the C-5 position. The photolysis of the former compound gave a C-nitroso compound which underwent a series of unusual intramolecular cleavages, deoximations, and redox reactions during the work-up. Stereoelectronic requirements for these intramolecular reactions are discussed. Thermolysis of N-chloro-endo-2-methylaminomethylbicyclo[2.2.2]oct-5-en in methanol also gave the product with azaisotwistane skeleton.

1,4‐Benzodiazepines III . Cyclization paths of hexaminium salts of 2‐chioroacetamido‐5‐ehlorobenzophenone and its N‐methyl derivative

AbstractThis study reports the isolation and characterization of hexaminium salts of 2‐chloroacetamido‐5‐chlorobenzophenone (I) and of 2‐(N‐methyl)chloroacetamido‐5‐chlorobenzophenone (II). The 7‐chloro‐1,3‐dihydro‐5‐phenyl‐2H‐1,4‐benzodiazepin‐2‐one (VI) and 7‐chloro‐1,3‐dihydro‐1‐meth‐yI‐5‐phenyl‐2H‐1,4‐benzodiazepin‐2‐one (VII), respectively are of pharmacodynamic importance. Based on chromatographic separation of some intermediates, and on spectrophotometric monitoring of cyclizations I → VI and II → VII, respectively, two different pathways for these reactions have been proposed. Since the slowest step in the reaction sequence II → VII follows the quasi first order rate law, intramolecular nucleophilic attack of the benzophenone carbonyl group on the hexamine moiety proved to be decisive for the cyclization (scheme II). However, cyclization I → VI seems to incorporate quite different solvolytic pathways in addition to one corresponding to the sequence II → VII. Isolated 4‐imidazolidinone intermediates N,N' ‐methylene‐bis[3‐{2 ‐benzoyl‐4‐chIoro)phenyI]‐4‐imidazolidinone(III), and 3‐(2 ‐benzoyl‐4′‐chlorophenyI)‐4‐imidazolidinone hydrochloride (IV) recyclize into the 1,4‐benzodiazepine VI. The optimal reaction conditions have been found to be between pH 6‐7.