The steric course of some electrophilic additions to the tetrahydropyridazine ring moiety of benzo[g]pyridazino[1,2-b]-phthalazine-6, 13-dione derivatives. II.

Abstract

The stereochemical features involved in electrophilic additions to the ring A moiety in diazatetracyclic analogues of anthracyclinones have been investigated. The 1-methyl and 1,3-dimethyl derivatives 2a and 2b were selected as the substrates and made to react with bromine azide, iodine azide, and NBS–EtOH in order to evaluate the influence of the C-1 substituent on the product distributions. Electrophilic attack at the C-2/C-3 double bond occurs mainly in the less hindered anti fashion. The nucleophilic step governs the stereochemistry of the reaction products. Conformational factors are predominant over the steric and electronic effects originated by the ring A substituents, since axial antiparallel attack of the nucleophile on the intermediate epihalonium ion is clearly preferred to the equatorial approach. Keywords: diazatetracycles, Diels–Alder reaction, electrophilic addition, anthracyclinone analogues, pyridazine ring.