Carbon Nucleophilicities of Indoles in S_NAr Substitutions of Superelectrophilic 7-Chloro-4,6-dinitrobenzofuroxan and -benzofurazan

Abstract

Superelectrophilic 7-chloro-4,6-dinitrobenzofuroxan (DNBF-Cl) and 7-chloro-4,6-dinitrobenzofurazan (DNBZ-Cl) are shown to undergo facile carbon-carbon couplings with a series of weak carbon nucleophiles consisting of a number of differently substituted indoles, 1,2,5-trimethylpyrrole and azulene, in acetonitrile. Despite the fact that steric effects preclude a coplanarity of the donor and acceptor moieties, the resulting substitution products are subject to an intense intramolecular charge transfer. A kinetic study of the various substitutions has been carried out. The absence of a significant dependence of the rates of coupling on the hydrogen or deuterium labeling at the reactive center of the nucleophiles indicates that the reactions take place through an SEAr-SNAr mechanism with the initial nucleophilic addition step being rate-limiting. A vicarious-type substitution is shown to be unreasonable. Referring to Mayr nucleophilicity parameters (N), which have become recently available for a large set of indoles, the electrophilicity of DNBF-Cl and DNBZ-Cl, could be ranked on the general electrophilicity scale E developed by this author (Acc. Chem. Res. 2003, 36, 66). With essentially similar E values of -6.1, these two compounds have an electrophilicity which approaches that of cationic stuctures such as 4-nitrobenzenediazonium cation or tropylium cations. Most important in the context of SNAr substitutions, DNBF-Cl and DNBZ-Cl are 7 orders of magnitude more electrophilic than picryl chloride, the conventional reference electrophile in this field. It is this so far unique behavior which allows the facile coupling of DNBF-Cl and DNBZ-Cl with such weak carbon nucleophiles as indoles. Based on a nice Brönsted-type correlation for 5-X-substituted indoles, the unknown pKaCH values measuring the Brönsted C-basicity of several N-benzylindoles could be readily estimated. The influence of some steric effects in 2-methylindole systems is pointed out.

Nucleophilic Substitution Reactions of 2‐Methoxy‐3‐X‐5‐nitrothiophenes: Effect of Substituents and Structure–Reactivity Correlations

“…Figure also reveals that the thiophenes 1a–d used in this study display an electrophilicity that compares well with that of 4‐(2,2‐bis‐(phenylsulphonyl)vinyl)‐ N , N ‐dimethylaniline 9 ( E = −16.53) , the substituted pyridinium salt 10 ( E = −17.90) , the 3‐methoxybenzaldehyde 11 ( E = −19.32) , and the diethyl 4‐methyl‐benzylidenemalonate 12 ( E = −21.11) , respectively, but lower than that of 1,3,5‐trinitrobenzene 8 ( E = −13.19) , the conventional aromatic electrophile in S N Ar processes and the 3,5‐difluoro‐substituted benzhydrylium ion 5 ( E = 8.02), the most electrophilic species known to date . Within the E scale developed by Mayr and co‐workers, the electrophilicity of the most reactive thiophene, i.e., 1a ( E = −17.18) appears to be higher than that of some benzylidenemalonate such as the substituted diethyl benzylidenemalonate 4 ( E = −23.80), but have an E value lower by 11 units than that of 7‐chloro‐4,6‐dinitrobenzofuroxan 6 and 7‐chloro‐4,6‐dinitrobenzofurazan 7 ( E = −6.11) .…”

“…The E values are listed and compared in Fig. with those obtained in previous studies by Terrier and co‐workers for 7‐chloro‐4,6‐dinitrobenzofuroxan 6 , 7‐chloro‐4,6‐dinitrobenzofurazan 7 , and 1,3,5‐trinitrobenzene 8 , together with substrates 4 , 5 , and 9–12 previously investigated by Mayr and co‐workers .…”

“…Within the E scale developed by Mayr and co-workers, the electrophilicity of the most reactive thiophene, i.e., 1a (E = −17.18) appears to be higher than that of some benzylidenemalonate such as the substituted diethyl benzylidenemalonate 4 (E = −23.80), but have an E value lower by 11 units than that of 7-chloro-4,6-dinitrobenzofuroxan 6 and 7-chloro-4,6dinitrobenzofurazan 7 (E = −6.11) [20].…”

“…encompasses a range of 38 orders of magnitude (−8.80 ≤ N ≤ 28.95 ):Recently, Terrier and co‐workers have investigated S N Ar reactions of 7‐chloro‐4,6‐dinitrobenzofuroxan 6 and 7‐chloro‐4,6‐dinitrobenzofurazan 7 with a series of weak carbon nucleophiles (substituted indoles, azulene, and 1,2,5‐trimethylpyrrole) and have demonstrated for the first time that it is possible to describe the second‐order rate constants through the relationship proposed by Mayr and co‐workers (Eq. ) .…”

Nucleophilic aromatic substitution in chlorinated aromatic systems with a glutathione thiolate model

“…Although several pathways and competing side‐reactions are possible, a substantial number of these reactions proceed through an addition‐elimination mechanism. Experimental evidence generally points to a two‐step process, which is dependent upon nucleophile, leaving group, and the presence of electron‐withdrawing substituents . In contrast, ab initio and semiempirical theoretical treatments reveal both two‐step and single‐step mechanisms …”