?Intramolecular Ortho-Arylation of Halobenzyl Aryl

MARÍA E. BUDÉN, ADRIANA B. PIERINI Y ROBERTO A. ROSSI.

Los Cocos, Córdoba

Conferencia; 9º Conferencia Latinoamericana de Físico-química Orgánica; 2007

INFIQC

     INTRAMOLECULAR ORTHO-ARYLATION OF HALOBENZYL ARYL AMIDE IONS VIA ELECTRON TRANSFER REACTIONS. REGIOCHEMICAL AND MECHANISTIC ANALYSIS.

 

Budén, María E.; Pierini, Adriana B. and Rossi, Roberto A.

 

Instituto de Investigaciones en Fisicoquímica de Córdoba (INFIQC).

Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, 5000, Córdoba, Argentina. E-mail: rossi@mail.fcq.unc.edu.ar 

 

Radicals are highly reactive species which can react by different mechanistic pathways. One of these paths, of relevance in synthetic organic chemistry, is the coupling with an anion to form a radical anion. This is one of the key steps of the S_RN1 mechanism[1] through which a nucleophilic substitution, mediated by electron transfer (ET) can be achieved.

Several nucleophiles have been shown to react by this means such as carbanions and anions from heteroatom which lead to the formation of new C-C or C-heteroatom bonds in good yields. Another example is the reaction of aromatic amide ions with aromatic substrates. In these reactions C-N and C-C bonds formation can be achieved instead.

These reactions have special interest for substrates that bears both, the leaving group and the nucleophilic center, as these compounds can afford a cyclic product by an intramolecular process. Related to this subject we have study the reaction of different secondary aromatic amides with a pedant ortho-halo benzyl halide moiety.

N-(2-iodobenzyl)benzenamine 1 does not react in liquid ammonia with an excess t-BuOK in the dark. Instead, under irradiation, phenanthridine 2 was obtained in 90% yield together with the reduced product  3 in 9% (Scheme 1). These results indicate that a photoinduced ET is needed for the reaction to occur. The reaction was partially inhibited by p-dinitrobenzene a well-known inhibitor of process mediated by radical anions, but it was not inhibited by radical traps, such as di-tertbutyl nitroxide or TEMPO. These facts suggest that the intramolecular coupling step is faster than the intermolecular reaction with the radical traps.

Reactions of a diverse set of ortho-halobenzylarylamides were studied. In order to explain the regiochemistry of these reactions a theoretical analysis was made with DFT methods (B3LYP/6-31+G*). The potential energy surface study revealed that the C-C ring closure reaction is thermodynamically and kinetically favored over C-N coupling.

 

[1] Rossi, R. A.; Pierini, A. B.; Peñéñory, A. B. Chem. Rev. 2003, 103, 71-167.