Direct Reductive Cyclocondensation of the Nitro Group with the Amido Group: Key Role of the Iminophosphorane Intermediate in the Synthesis of 1,4-Dibenzodiazepine Derivatives

Abstract

A class of dialkylamino-substituted dibenzodiazepines and their hetero analogues was synthesized by the intramolecular aza-Wittig condensation of the amido group with iminophosphoranes. The one-pot, two-step procedure includes reductive synthesis of the intermediate iminophosphoranes from the corresponding nitroamides and tributylphosphine.

Synthesis of Benzodiazepines Through Ring Opening/Ring Closure of Benzimidazole Salts

“…In addition, the aforementioned resulting products also suffered from poor site selectivity at the two NH units with pyrido‐benzodiazepine for further N‐functionalization (Scheme , pathway 1). To overcome above disadvantage in pathway 1 caused by ortho ‐phenyldiamine, various coupling partners, such as ortho ‐nitroaniline, 2‐chloropyridin‐3‐amine, 2‐aminobenzoic acid, methyl 2‐aminobenzoate, 2‐bromobenzamide, as well as three‐component systems, have been used to displace the ortho ‐phenyldiamine for the synthesis of pyrido‐benzodiazepine compounds, with a focus on achieving high selectivity (Scheme , pathway 2).…”

Recent Advances in the Synthesis of Heterocycles by the Aza-Wittig Reaction

“…Wróbel and co-workers in 2019 used a one-pot, twostep process based on the intramolecular aza-Wittig reaction to produce new 1,4-dibenzodiazepines 64 (Scheme 14). 24 In this protocol, tributylphosphine (21) This route 24 was used to synthesize clozapine (66), a prominent drug typically used to treat schizophrenia, containing the dibenzodiazepine scaffold (Figure 4). Its key merits are that it is a shorter, uncatalyzed, and metal-free strategy, compared to previous approaches.…”

Discovery of EDA-Complex Photocatalyzed Reactions Using Multidimensional Image Processing: Iminophosphorane Synthesis as a Case Study

“…36 Other methods can also be employed including the use of halogenating 37 or oxidizing agents, 38,39 alkylation of aminophosphoranes, 40 and condensation of N-aryl 2-nitrosoanilines 41 or 2nitroadiarylamines (Figure 4b, Equation f-j). 42,43 The transformation of nitroarenes into iminophosphoranes via thermal conditions has been extensively studied by Wróbel's group. 43 A mixture of nitroarenes with an excess of triphenylphosphine (5-10 equivalents) at high temperatures (150-220 °C) produced the corresponding iminophosphorane in 27-97% yields after up to 12 h of stirring.…”

“…42,43 The transformation of nitroarenes into iminophosphoranes via thermal conditions has been extensively studied by Wróbel's group. 43 A mixture of nitroarenes with an excess of triphenylphosphine (5-10 equivalents) at high temperatures (150-220 °C) produced the corresponding iminophosphorane in 27-97% yields after up to 12 h of stirring. Therefore, the discovery that we present in this study is remarkable as it can be performed in mild and photocatalyzed conditions, increasing the options for iminophosphorane synthesis.…”