Study on Synthesis of Benzothiazole Compounds Enabled by DMSO-Promoted C-H Sulfidation/cyclization

Author:Zhu Xiao Ming

Supervisor:liang yun

Database:Doctor

Degree Year:2019

Download:26

Pages:226

Size:5281K

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Benzothiazole derivatives are important heterocyclic compounds,which are widely used in various fields such as pharmaceutical chemistry,organic chemistry,biological chemistry,and industrial and agricultural chemistry.So it is of great significance to study their synthesis methods for synthetic chemists.The traditional methods for the synthesis of benzothiazole derivatives have the following shortcomings:(1)toxic and smelly organic sulfur reagents provide sulfur sources for construction of C/S bond;(2)the C-S bond is constructed by using C-X bond(X=halogen or pseudo-halogen),which increases the discharge of waste;(3)the reaction conditions are harsh and complex.Therefore,it has become a concern of researchers for the development of a method with atomic economy,mild reaction conditions and reduction of substrate derivatization reaction steps to synthesize benzothiazole compounds.In the paper,under transition-metal-free conditions,using inorganic sulfur as sulfur source and DMSO as oxidant,the development of new methods for a green and efficient method for the synthesis of benzothiazole compounds based on C-H sulfidation/cyclization reaction were studied.The detailed researches were described as follows:1.Under catalyst-free and additive-free conditions,various2-substituted naphtho[2,1-d]thiazole and 2-phenylbenzothiazole derivatives were synthesized in moderate to excellent yields by the reaction of N-substituted aromatic amines with sulfur under DMSO oxidant.This reaction realizes the sulfidation/cyclization of intramolecular C(sp3)-H and C(sp2)-H promoted by DMSO,with the C-S bond constructed twice.It has good functional group compatibility and substrate applicability.2.Under catalyst-free and additive-free conditions,the 2-substituted naphtho[2,1-d]thiazole and 2-phenylbenzothiazole derivatives were synthesized in moderate to excellent yields by the reaction of three-component(aromatic amine,benzylamine derivative and sulfur).The reaction mechanism shows that the reaction has experienced the cleavage and binding of two C-N bonds,as well as the construction of two C-S bonds,through the intermolecular C(sp3)-H and C(sp2)-H sulfidation/cyclization reaction promoted by DMSO.It is one of the advantages of the reaction that various functional groups can be tolerated well under this reaction condition.3.In the oxidation system of I2/DMSO,the 2-substituted naphtho[2,1-d]selenazolesand2-phenylbenzoselenazolederivativeswere synthesized efficiently by the reaction of N-substituted aromatic amines and selenium in chlorobenzene solvent.This reaction realizes the selenization/cyclization of intramolecular C(sp3)-H and C(sp2)-H promoted by DMSO,with the C-Se bond constructed twice.The reaction has the advantages of mild reaction conditions,simple raw materials and better functional group compatibility.4.Under catalyst-free and additive-free conditions,a green synthesis method of thiobenzothiazolidones was developed by the reaction of three components of K2S,DMSO and o-iodoaniline derivatives.The experimental results show that:(1)the sulfur source of the products comes from K2S;(2)DMSO not only acts as oxidant,but also provides carbon source for the product.It is worth mentioning that the same strategy could be used for the synthesis of thioureas from primary diamines.Therefore,the synthesis method can be used as a general method for the construction of thiocarbonyl groups.5.Benzothiazoles were synthesized by the reaction of three components of K2S,DMSO and o-iodoaniline derivatives under involving ammonium acetate.The method has the advantages of fewer reaction steps,mild reaction conditions and functional group tolerance.Meanwhile,benzimidazoles can also be synthesized by using similar strategies.