Method for synthesizing poly-substituted 2-aryl benzothiazoles by utilizing thiourea as sulphur source

Abstract

The invention discloses a method for synthesizing poly-substituted 2-aryl benzothiazoles by utilizing thiourea as a sulphur source. According to the method, thiourea reacts with benzyl chloride to generate an S-benzylisothiourea salt in situ. After that, through the aromatic nucleophilic substitution reaction of the obtained S-benzylisothiourea salt with 2-fluoronitrobenzene and then the one-step reduction (one-pot reaction) process, o-amino phenyl benzyl thioether as an intermediate product can be obtained. Finally, through the iron-catalyzed cross-dehydrogenative-coupling reaction of the o-amino phenyl benzyl thioether, a target product can be obtained. Compared with the traditional synthetic method, the method has the significant advantages of (1) short reaction step, wherein the target product can be synthesized through only three steps of simple reactions by utilizing simple chemical raw materials; (2) mild reaction condition, high atom economy, and relatively safe and cheap reaction reagents; (3) high reaction yield, good substrate tolerance and free of any dangerous or high-toxicity reagent. Therefore, the method might be applied to the large-scale production.

Description

technical field [0001] The invention belongs to the field of organic synthesis, and in particular relates to a synthesis method of multi-substituted 2-arylbenzothiazoles. Background technique [0002] Multi-substituted 2-arylbenzothiazoles have a wide range of applications in the fields of synthesis, medicine, and materials chemistry. Many molecules containing 2-arylbenzothiazole structures have very important biological activities, such as antitumor drugs, fatty acids Amidohydrolase inhibitors and selective hormone receptor modulators, etc. There are three main methods for the synthesis of common multi-substituted 2-arylbenzothiazoles: (1) preparation by condensation of 2-aminothiophenol (or bis(2-aminophenyl) disulfide) and benzaldehyde (J.Med . Chem. 2005, 49, 179; Tetrahedron Lett. 2014, 55, 6543.). (2) Use benzothiazole as raw material to directly synthesize the target product through transition metal-catalyzed C-H activation reaction (Tetrahedron Lett. 2015, 56, 693;...

AI Technical Summary

Problems solved by technology

The raw materials (2-aminothiophenol and bis(2-aminophenyl) disulfide) in the first method are relatively expensive, and some dangerous and highly toxic reagents (such as bromine and thiocyanate, etc.) need to be used Synthesized by multi-step reaction, and the reaction selectivity is poor and the yield is general

The reaction conditions of the latter two methods are relatively harsh. Generally, some toxic noble metal catalysts need to be added. At the same time, many raw materials such as substituted benzothiazoles and o-halophenylaryl thioamides need to be prepared in advance. The cost is relatively high, and the range of reaction substrates limited

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