Stable-Ion NMR and GIAO-DFT Study of the Carbocations from Benzofluorenes and Dibenzofluorenes; Synthesis of Nitro Derivatives; Mutagenicity Assay and X-ray Analysis

Abstract

First examples of stable carbocations are reported from 7H-benzo[c]fluorene (2), 11H-benzo[b]fluorene (3), 11H-benzo[a]fluorene (4), 2-methoxy- (5), 7-methoxy- (6), and 9-methoxy-11H-benzo[a]fluorene (7), 7H-dibenzo[c,g]fluorene (8), 13H-dibenzo[a,g]fluorene (9), 2-methoxy-13H-dibenzo[a,g]fluorene (10) and 5,6-dihydro-13H-dibenzo[a,g]fluorene (11). Charge-delocalization modes in the resulting carbocations were derived based on experimental and/or computed (GIAO-DFT) Δδ¹³C values and through the NPA-derived changes in charges (Δq). Whereas protonation regioselectivity in the parent systems (2, 3, 4, 8, and 9) corresponds to the energetically most favored carbocations computed by DFT, selectivity in the OMe-substituted derivatives (5, 6, 7, 10, and 11) is strongly controlled by the methoxy group. Benzofluorenes 3, 5, 6, and 7 and dibenzofluorenes 8, and 10 were nitrated under very mild conditions. Nitration selectivity in the parent systems 3 and 8 parallels those in stable-ion protonation, whereas regioselectivity in the MeO derivatives (6, 7, and 10) corresponds more closely to relative arenium ion energies in the parent unsubstituted systems. Comparative mutagenicity assays (Ames tests) were performed on 3NO₂, 5NO₂, 7NO₂, 8NO₂, and 10NO₂ relative to their precursors. Compounds 10NO₂, 7NO₂, and 8NO₂ were found to be potent direct-acting mutagens (with 10NO₂, 8NO₂ also capable of acting as potent indirect mutagens). The X-ray structures of 5NO₂ and 8NO₂ were determined. The angle between the plane of the nitro group and the aromatic ring bearing the NO₂ group is 89.4° in 5NO₂ and 32.4° in 8NO₂. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)