Study On New Methodologies For The Synthesis Of Five-membered Aromatic Heterocycles

Aromatic heterocyclic compounds,frequently found in natural products,is a class of organic compounds with important application value,which are widely used in many fields such as medicine,agriculture,materials,and daily chemicals,etc.Therefore,the construction of aromatic heterocycles is an important research area in organic synthesis,which has attracted great interest from researchers.Among them,benzothiazole,pyrrole,furan and thiophene derivatives are the most common and important aromatic heterocyclic compounds.So far,although there are many methods for constructing such heterocyclic compounds in the literature,some problems are still existed,such as harsh reaction conditions,serious pollution,and tedious work-up procedures.Therefore,in this paper,we mainly focus on the synthesis of these four heterocyclic compounds,developing an efficient,low pollution,and universal synthesis method to solve this problem.At the beginning of the paper,the important roles of benzothiazoles,pyrroles,furans,and thiophenes and development status of their synthetic methods were summarized firstly through literature review.On this basis,we proposed the idea of generating benzothiazole compounds via a three-component reaction,and synthesizing common five-membered heterocyclic rings in a“one-pot and two-step method”.The specific achievements of this paper are as follows:1.We have achieved a three-component aerobic oxidation reaction promoted by acetic acid.Using this strategy,we have synthesized a series of complex 2-thioarylbenzothiazoles with high selectivity.In this reaction,easily available 2-aminothiophenols,?,?-unsaturated aldehydes,and various aryl thiophenols were used as substrates for the construction of benzothiazole heterocycles with oxygen as a green oxidant and acetic acid as a promoter.Mild conditions,simple operation,no transition-metal involvement,wide range of substrates,and good functional group compatibility make this method very practical for the synthesis of various complex natural products and biomedical active molecules.At the same time,the reaction has a complete regioselectivity,providing a powerful method for the synthesis of complex molecules.2.By linking the reaction of the oxidative coupling of the carbonyl?-Csp~3-H of aryl acetones catalyzed by the inexpensive transition-metal Cu to 1,4-diketone compounds and the classic Paal-Knorr reaction,we studied the synthesis of pyrroles,furans and thiophenes by"one-pot and two-step method".After a series of conditions screening,the C(sp~3)-C(sp~3)coupling of aryl acetones was developed in cyclohexane to synthesize 1,4-diketone compounds using inexpensive copper pivalate as a catalyst,2,2'-bipyridine as a ligand,and di-tert-butyl peroxide as an oxidant.We initially expanded the substrate of this reaction with good yields.Further,the Paal-Knorr reaction will be performed in situ under the addition of additives for the synthesis of five-membered aromatic heterocyclic compounds.