Ranking the Reactivity of Superelectrophilic Heteroaromatics on the Electrophilicity Scale

Abstract

The kinetics of the reactions of a series of reference carbon nucleophiles, consisting of N-methylpyrrole A, indole B, N-methylindole C, and enamines D-G, with 10 electron-deficient aromatic and heteroaromatic substrates (1-10), resulting in the formation of stable anionic sigma-adducts, have been investigated in acetonitrile at 20 degrees C. It is shown that the second-order rate constants k(1) pertaining to the carbon-carbon coupling step of these processes fit nicely the three-parameter equation log k (20 degrees C) = s(N + E), allowing the determination of the electrophilicity parameters E of 1-10 and therefore the ranking of these neutral electron-deficient compounds on the comprehensive electrophilicity scale defined for cationic electrophiles by Mayr et al. (Mayr, H.; Kempf, B,; Ofial, A. R. Acc. Chem. Res. 2003, 36, 66). The E values of 1-10 are found to cover a range from -13 to -5, going from 1,3,5-trinitrobenzene 1, the least reactive molecule, to 4,6-dinitrotetrazolo[1,5-a]pyridine 8, 4-nitro-6-trifluoromethanesulfonylbenzofuroxan 3, and 4,6-dinitrobenzofuroxan 2, the three most reactive heterocycles. Of major interest is that the E value of 2 is essentially the same as that for 4-nitrobenzenediazonium cation (E = -5.1), approaching that of the tropylium cation family (E approximately -3 to -6) as well as a number of metal-coordinated carbenium ions. Such a ranking holds promise for expanding the range of coupling reactions which can be envisioned with such strongly electron-deficient neutral heteroaromatics as nitrobenzofuroxans and related compounds. Arguments are also given which exclude the possibility for the reactions studied to proceed via an electron-transfer mechanism.

Synthesis and Characterization of Novel Quinone Methides: Reference Electrophiles for the Construction of Nucleophilicity Scales

“…The electrophilic reactivities of the parent quinone methides o-QM and p-QM are comparable to those of stabilized carbocations (tropylium ion, E = -3.7), [10b] i.e., they are more electrophilic than Terrier's superelectrophiles which have so far been considered the strongest neutral nucleophiles. [25] In contrast, the substituted para-quinone methides 2 and 3 are much less reactive (-18.0 Ͻ E Ͻ -11.5) comparable to other Michael acceptors [22,26] or electron-deficient arenes.…”

“…[12g, 25,27] The influence of different 2,6-substituents R on the electrophilicity of aryl-substituted quinone methides can be illustrated by comparing the 4-(dimethylamino)phenyl-substituted compounds 2b, 3e, 3f, and 3b (Scheme 9).…”

Farewell to the HSAB Treatment of Ambident Reactivity

“…[49] Nitrogen is also the preferred site of attack of trinitrobenzene at aniline. [50] From E = À13.2 [51] for trinitrobenzene (10) and N % 4, s N = 0.8-1.0 for the para position of aniline, one can estimate rate constants in the range of 4 10 À8 to 7 10 À10 m À1 s À1 for the attack of trinitrobenzene at the aromatic ring of aniline. From these rate constants one can derive that the attack of trinitrobenzene at the para position of aniline (electrophilic aromatic substitution) would have half-reaction times of 1 to 50 years in 1m solutions of the reactants at 20 8C.…”

Abschied vom HSAB‐Modell ambidenter Reaktivität

“…[49] Das Stickstoffatom ist auch die bevorzugte Position des Angriffs von Trinitrobenzol auf Anilin. [50] Aus E = À13.2 [51] für Trinitrobenzol (10) Trinitrobenzol auf die p-Position von Anilin (elektrophile aromatische Substitution) bei 20 8C eine Halbreaktionszeit zwischen 1 und 50 Jahren in 1m Lösungen der Reaktanten haben sollte. Entsprechend wurde eine Umlagerung des sAddukts 12 in das Biphenyl-Derivat 11 nicht beobachtet (Schema 15).…”