Electrophilic chemistry of thia-PAHs: stable carbocations (NMR and DFT), S-alkylated onium salts, model electrophilic substitutions (nitration and bromination) and mutagenicity assay.

LAALI, KENNETH K.; CHUN, J.-H.; OKAZAKI, T.; KUMAR, S.; BOROSKY, GABRIELA L.; SWARTZ, C.

JOURNAL OF ORGANIC CHEMISTRY

American Chemical Society

Año: 2007 vol. 72 p. 8383 - 8393

0022-3263

First examples of stable carbocations are reported from several classes of thia-PAHs with four fused rings, namely benzo[b]naphtha[2,1-d]thiophene (1), and its 3-methoxy-derivative (2), phenanthro[4,3-b]thiophene (3) and its 7-methoxy- (4), 10-methoxy- (5) and 9-methoxy- (6)derivatives,  phenanthro[3,4-b]thiophene (7) and its 7-methoxy- (8) and 9-methoxy- (9) derivative, and 3-methoxybenzo[b]naphtha[1,2-d]thiophene (11). In several cases the resulting carbocations were also studied by GIAO-DFT. Charge delocalization modes in the resulting carbocations were probed. A series of S-alkylated onium tetrafluoroborates namely 1Me+, 1Et+, 2Et+, and 7Me+ (from 1, 2 and 7), 10Me+ and 10Et+ (from benzo[b]naphtha[1,2-d]thiophene 10), 12Me+ and 12Et+ (from phenanthro[3,2-b][1]benzothiophene 12), 13Me+ (from 3-methoxyphenanthro[3,2-b]benzothiophene 13), 14Me+ (from phenanthro[4,3-b][1]benzothiophene 14) were synthesized. PAH-sulfonium salts 1Me+, 1Et+, 10Me+, 10Et+, 12Me+, and 14Me+ proved to be efficient akylating agents towards model nitrogen bases (imidazole and azaindole). Facile transalkyation to model nucleophiles (including guanine) is also supported by favorable reaction energies computed by DFT.  Ring opening energies in thia-PAH-epoxides from 1, 3, and 7, and charge delocalization modes in the resulting carbocations were also evaluated. The 4-ring fused thia-PAHs 1, 2, 3, 4, 5, 7, 8, and 11 are effectively nitrated under extremely mild conditions. Nitration regioselectivity corresponds closely to protonation under stable ion conditions. Bromination of 4 and 6 are also reported. Comparative mutagenicity assays (Ames test) were performed on 1 versus 1NO2, 5 versus 5NO2 and 11 versus 11NO2. Compound 11NO2 was found to be a potent direct acting mutagen.