A method for synthesizing key intermediates of astemizole and derivatives thereof

Abstract

The invention discloses a method for synthesizing an astemizole key intermediate and a derivative thereof. A fluorescence labeling non-metal organic boron-nitrogen lewis acid and base bifunctional compound is adopted as a catalyst, so that pollution caused by heavy metals is effectively avoided; the catalyst can be reclaimed and repeatedly used, and residue amount of the catalyst in a product can be quickly detected; and raw materials are wide in resource, selectivity and yield of a target product are approximate to 100 percent, the catalyst can be repeatedly used for a plurality of times, reaction condition is simple, reaction is easy to operate, cost is low, and a preparation process is green and environmentally friendly.

Description

【Technical field】 [0001] The invention belongs to the field of catalytic organic synthesis, in particular to a method for synthesizing key intermediates of astemizole and derivatives thereof. 【Background technique】 [0002] Astemizole, as a potent and long-acting H1 receptor antagonist, is often used in our daily life. The most important key intermediate of astemizole is benzimidazole derivatives, the structural formula is as follows: [0003] [0004] However, there are still difficult challenges in the process of synthesizing benzimidazole derivatives. The traditional synthetic method is obtained by the ring-closing reaction of o-phenylenediamine and carboxylic acid under strong acid as a catalyst. This method uses strong acid, such as concentrated HCl, concentrated H 2 SO 4 etc., thus some substrates sensitive to strong alkali are not applicable, and also cause certain environmental pollution to the environment. The improved method is to react o-phenylenediamine wi...

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Problems solved by technology

where the catalyst / oxidant is I 2 、H 2 o 2 、H 2 SO 4 / SiO 2 etc. The disadvantage of this method is that the catalyst cannot be recycled and reused, and the time is relatively long, which neither meets the requirements of energy saving nor atomic economy.

The recently reported synthesis of a series of benzimidazole derivatives using organic bismuth Lewis acid catalysis is simple to operate and has a high yield. However, metal bismuth is introduced in the reaction, and there are unavoidable metal residues in the product, and there is no effective detection. method

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