Metal-Free Synthesis of Benzimidazoles via Oxidative Cyclization of d-Glucose with o-Phenylenediamines in Water

Abstract

D-Glucose has been identified as an efficient C1 synthon in the synthesis of benzimidazoles from o-phenylenediamines via an oxidative cyclization strategy. Isotopic studies with 13 C 6 -D-glucose and D 2 O unambiguously confirmed the source of methine. The notable features of this method include the following: broad functional group tolerance, a biorenewable methine source, excellent reaction yields, a short reaction time, water as an environmentally benign solvent, and the synthesis of vitamin B 12 component on the gram scale.

Copper‐Catalyzed Oxidative C−C Cleavage of Carbohydrates: An Efficient Access to Quinazolinone Scaffolds

“…Based on the limited studies, a plausible reaction mechanism was postulated as presented in Scheme 7A & B. The cyclic hemiacetal 2 a will exist in equilibrium with its open-chain aldehyde form 2a' [9,10] The initial step involves the condensation of compound 1 a with aldehyde 2a' to give the imine intermediate In the alternative pathway, the initial step involves the formation of glucose fragmented products like formic acid F, and glycolic acid G through CuBr/DMSO catalyzed oxidative CÀ C cleavage. [16d] Next, these platform chemicals react with compound 1 to form imines H and I.…”

“…Initial reaction was carried out with 2‐amino‐ N ‐phenylbenzamide ( 1 a ) and D ‐glucose ( 2 a ) under our previously reported conditions [10] . Unfortunately, the desired product 3 a was formed in less yield along with unreacted 1 a , and some unidentified products [11] .…”

“…Initial reaction was carried out with 2-amino-N-phenylbenzamide (1 a) and D-glucose (2 a) under our previously reported conditions. [10] Unfortunately, the desired product 3 a was formed in less yield along with unreacted 1 a, and some unidentified products. [11] Further optimization studies were performed as presented in Table 1 to obtain the desired product in high yields.…”

“…[9] Later, we developed the synthesis of benzimidazoles from o-phenylenediamine derivatives with carbohydrates as methine source in water conditions using TBHP as an oxidant (Scheme 2b). [10] Despite these progresses, there are no literature precedence to utilize maximum number of carbons in D-glucose as C 1 synthon towards the construction of heterocycles under transition-metal catalysis. In this context and our research focus on renewable resources for heterocyclic synthesis, herein we report an atomeconomical and environmentally benign approach for the synthesis of quinazolinones and benzoimidazoquinazoline using 0.25-0.50 equiv., of D-glucose with cat.…”

Recent Progress in Synthesis of Polysubstituted Imidazoles by Cyclization Reaction

“…Plausible mechanism for the synthesis of imidazole from o-nitroanilines and alcohols 2020 年, Senadi 课题组[55] 报道了一种在温和、无金 属的以水为溶剂的反应条件下, 用 D-葡萄糖作为次甲 基源, 邻苯二胺通过氧化环化策略, 在短时间内以良好 到优异的产率合成苯并咪唑化合物 86 的方法(Scheme 37邻苯二胺和 D-葡萄糖合成咪唑 Scheme 37 Synthesis of imidazole from o-phenylenediamines and D-glucose 同年, 林媚和柯方课题组[56] 报道了一种用廉价易 得、易处理的曙红 Y 为光催化剂, 以邻苯二胺和苯腈为 原料, 在水相中通过自由基环化反应合成苯并咪唑化合 物 87 的方法(Scheme 38). 该体系对脂肪族和含杂环的 腈类化合物都同样适用.…”