Use of Vitamin B₁₂ as a Nontoxic and Natural Catalyst for the Synthesis of Benzoxazoles via Catechols and Primary Amines in Water under Aerobic Oxidation

Abstract

We report an efficient and environmentally friendly approach for the synthesis of benzoxazoles in water using vitamin B 12 (2 mol %) as a nontoxic and natural catalyst under ambient air as the oxidant. To achieve this goal, benzoxazoles were prepared in relatively high yields by the reaction of catechols with amines under air at 50 °C in the presence of vitamin B 12 . This work is the first report on the incorporation of a natural cobalt complex as a redox catalyst for the oxidation of catechols. Also, we applied gabapentin and tranexamic acid, with an amine functional group, known as to have anticonvulsant and analgesic activity and to prevent heavy bleeding, for the synthesis of benzoxazoles with good results. The significant features of this procedure for the preparation of benzoxazoles include the use of water as a green and attractive solvent in an organic reaction, the use of ambient air as a benign sole oxidant due to its abundance, low cost, mild conditions, environmentally friendly, the use of a biodegradable catalyst, no moisture sensitivity, simple workup procedure, and simple recovery and recyclability of the catalyst without a significant decrease in activity, which all together make this approach in line with the 12 principles of green chemistry. These aforementioned features make the current approach attractive for academic research as well as industrial applications.

Iodine-catalyzed synthesis of benzoxazoles using catechols, ammonium acetate, and alkenes/alkynes/ketones via C–C and C–O bond cleavage

“…It seems that catechol (I) is converted into mono-quinone (II) in the presence of the I 2 -DMSO catalyst system. 32,35 The condensation reaction of II with ammonium acetate generates o-iminocyclohexadiene alcohol (III). 35 The generation of intermediate (IV) is possible by another condensation reaction of the imine group and carbonyl group of acetophenone.…”

“…In continuation of our program on the synthesis of benzoxazole derivatives, 31,32,34,36 we would like to introduce a metal-free one-pot multi-component method for the efficient synthesis of 2-aryl benzoxazoles.…”

“…For all of the reported methods for the synthesis of benzoxazoles using catechols, a transition metal-catalyzed process was applied. Coupling reaction of catechols with amines using copper 29,30 /iron 31 /Co, 32 with amino acids using silver 33 /iron, 31 with aldehydes and ammonium acetate using iron 34 /NaIO 4 35 and with benzyl alcohol using iron 36 are the available methods for the metal-catalyzed synthesis of benzoxazoles using catechols (Scheme 1A).…”

Iodine and DMSO as Surrogate of Hazardous Metal and Non‐Metal Reagents in Organic Synthesis

“…Several synthetic methods have been reported for their synthesis, [466–473] but those using catechol have received much attention. Various methods involving metals like iron and copper, and reagents like vitamin B 12 have been reported for benzoxazole synthesis using catechol and amines (Scheme 50 (a–d)) [474–477] . Benzoxazole has also been synthesized using benzyl alcohol and catechol with iron nitrate (Scheme 50 (g)) [478] .…”

“…Various methods involving metals like iron and copper, and reagents like vitamin B 12 have been reported for benzoxazole synthesis using catechol and amines (Scheme 50 (a-d)). [474][475][476][477] Benzoxazole has also been synthesized using benzyl alcohol and catechol with iron nitrate (Scheme 50 (g)). [478] For the synthesis using benzaldehyde and catechol, either Fe(III)-salen complex or NaIO 4 with NH 4 OAc as a nitrogen source is required (Scheme 50 (e) and (f)).…”