3,3'-Diindolylmethanes (DIMs) are an important class of indole alkaloids that exhibit antiinflammatory and anti-cancer effects. Herein, we report on a new, mild and efficient copper(II)-promoted decarboxylative coupling reaction of 2-(1H-indol-3-yl)acetic acid derivatives (1 a-h) with a variety of (substituted) indoles (2 a-t) yielding (un)symmetrically substituted DIMs (3 a-z, 3 aa-ai). Reaction of 2-(1Hindol-3-yl)acetic acid (1 a) with 7-azaindole led to the 3,3'-connected DIM analog 5 d, while 4-, 5-, and 6azaindoles and benzimidazole reacted at the N1-nitrogen atom. Reaction of 1 a with 1H-indazoles led to a mixture of 1-and 2-substituted indazole derivatives. The new method allows large-scale synthesis of biologically active DIMs. Scheme 2. Decarboxylative coupling reaction of 1 a with azaindoles 4 a-d. Scheme 3. Decarboxylative coupling of 1 a with 1H-benzimidazole (6 a). Scheme 4. Decarboxylative coupling reaction of 1 a and 1 d with 1H-indazole derivatives (8 a-b).
This article indicated a novel methodology of evaluation of steric effect of (hydroquinone (HQ), tert-Butyl hydroquinone (TBHQ) and 2, 5-ditert-butyl hydroquinone (DTBHQ)) by using a Briggs-Rauscher chemical oscillating system. The macro cyclic [NiL](ClO 4) 2 complex catalyst with 5,7,7,12,14,14-hexamethyl-1,4,8,1,1-tetraazacyclotetradeca-4,1,1-diene as ligand is used. The calculated experimental data confirmed the diverse perturbation effects of all three additives towards the active Briggs-Rauscher oscillator in their concentration ranges from 5.0 × 10-7 M to 1.25 × 10-5 M. Hydroquinone generate inhibition time (t in) higher than t-BHQ, whereas, no influence of 2,5-DBHQ were observed in Briggs-Rauscher system. Our claim for such differences in perturbation is due to the strong steric hindrance effect of these additives. The presence of bulky group (tertiary butyl) reduces the reactivity of the antioxidants by covering the active sides (OH-group) from the attack of HOO • radical. Thus, Hydroquinone produced larger t in because of absence of bulky group, the shorter t in of t-BHQ due to the presence of one bulky group whereas, no t in of 2, 5-DBHQ because of two bulky groups attached. The perturbation reaction mechanism was discussed on the basis of FCA (Furrow-Cervellati-Amadori) model. The explanation mechanism is that both HQ and t-BHQ is oxidized by HOO • into their respective Quinone.
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