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Stable Ion and Electrophilic Substitution (Nitration and Bromination) Study of A‐Ring Substituted Phenanthrenes: Novel Carbocations and Substituted Derivatives; NMR, X‐ray Analysis, and Comparative DNA Binding
Author(s) -
Brulé Cédric,
Laali Kenneth K.,
Okazaki Takao,
Musafia Tamara,
Baird William M.
Publication year - 2007
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200600780
Subject(s) - chemistry , nitration , protonation , substituent , electrophilic substitution , carbocation , nitro , electrophilic aromatic substitution , medicinal chemistry , halogenation , ring (chemistry) , stereochemistry , thiophene , organic chemistry , ion , alkyl
Persistent carbocations were generated from five A‐ring mono‐ and di‐substituted phenanthrenes [3‐OMe; 4‐OMe, 1,3‐bis(OMe), 2,4‐bis(OMe), and 1,3‐bis(Me)]. In all cases protonation occurs in the A‐ring, ortho/para relative to methoxy or methyl substituent(s). Complete NMR assignments of the resulting carbocations are reported and their charge delocalization modes are discussed. Mild nitration (with 20–50 % aqueous HNO 3 at –10 °C or at room temp.) and bromination (NBS/MeCN/room temp.) of these substrates resulted in the synthesis of several novel mononitro‐/dinitro‐ as well as monobromo/dibromo derivatives, including those with nitro or bromo substituent in the bay‐region. Correspondence between the site of attack in low‐temperature protonation study and nitro substitution in ambient mild nitrations are examined. Complete NMR assignments for the new derivatives are reported as well as X‐ray structures for 2,4‐dimethoxy‐1‐nitro‐ and 1,3‐dimethyl‐4‐nitrophenanthrenes. A comparative DNA binding study with MCF cells on three of the synthesized mononitro and one dinitro derivative showed that 1,3‐dimethyl‐9‐nitro‐ (nitro at the meso position), 3‐methoxy‐4‐nitro‐ (nitro in bay‐region), and 1,3‐dimethoxy‐4,9‐dinitrophenanthrenes (nitro in both meso and bay‐regions) formed DNA adducts. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)