Study On C-S Bond Formation Reaction Involving Pyrazole Heterocycles

Pyrazoles,as five-membered heterocyclic compounds with special biological activity,play an important role in various fields such as pesticides and pharmaceuticals.In recent years,the synthetic methods concerning the involvement of pyrazoles in the construction of organic aromatic heterocyclic derivatives have achieved rapid development.Among them,the construction of asymmetric aryl sulfides by direct C-H functionalization of pyrazole heterocyclic compounds is one of the hot research topics.It has received wide attention because of its advantages,such as good atomic economy,easy availability of substrates,mild reaction conditions,and metal-free catalyst.Accordingly,it is of great interest to develop efficient and green methods for the synthesis of pyrazole-containing heterocyclic derivatives.Based on this,this thesis is devoted to the study of reactions for the selective construction of C-S bond by direct C-H functionalization using pyrazole heterocyclic compounds as substrates without transition metal catalysis and to provide a more facile and environmentally friendly synthetic system.The specific work is as follows:First,a green synthetic system for the C4-thioetherification reaction of 4-iodo-1H-pyrazol-5-amine with aryl sulfonyl hydrazides in water is presented.The C-S bond was selectively constructed at the C4position of the aminopyrazole by direct C-H activation under metal-free catalytic conditions using aminopyrazole and aryl sulfonyl hydrazide as substrates.The system was developed in the absence of any external catalyst,and a series of 4-iodo-1H-pyrazol-5-amine reacted smoothly with aryl sulfonyl hydrazides,prompted by a series of 4-iodo-1H-pyrazol-5-amine with mono iodine generated by heat as the catalyst.The reaction has a wide range of substrate suitability,and aryl sulfonyl hydrazides containing a variety of different substituent groups（electron-donating,electron-absorbing,thick rings,heterocycles）can be reacted with aminopyrazoles to obtain the target products in good or excellent yields,which are simple to operate under mild conditions and environmentally friendly.Secondly,the C3-thiocyanation of pyrazolo[1,5-a]pyrimidin-7-amine with KSCN was developed.Twenty-seven C3-thiocyanation products were synthesized with moderate to excellent yields.The reaction mechanism showed that the oxidation of K₂S₂O₈led to the formation of thiocyanate radical intermediates by potassium thiocyanate and further radical substitution reactions with pyrazolo[1,5-a]pyrimidin-7-amine molecules.In addition,it was found that the reaction could also proceed smoothly when a protecting group was present on the amino group at the C7 position to obtain the target product in excellent yields.This scheme is characterized by mild reaction conditions,cheap and easy availability of thiocyanation reagents,and a wide range of substrates for gram-scale synthesis.This direct C3-thiocyanation strategy provides an alternative approach for the synthesis of novel pyrazolo[1,5-a]pyrimidine-7-amine derivatives.It simultaneously promotes the development of pyrazolo[1,5-a]pyrimidin-7-amines in heterocyclic and medicinal chemistry.