Synthesis Of Hydroxybutynamides And 2-amino-6-styrenyl-pyrimidines

Calcium carbide is used to produce acetylene gas after hydrolysis in industry,then acetylene is used for further synthesis of some multifunctional molecules and drug molecules.However,most reactions involving the use of acetylene gas are complex,requiring high pressure equipment and difficult post-processing operation.As a result,many reactions involving acetylene gas are more or less defective.Recent studies show that the traditional acetylene gas can be replaced by cheap and easy-to-operate solid calcium carbide in organic synthesis directly or indirectly.These methods simplify the complex steps and equipment in the chemical production process,thus greatly reducing the production cost,and reducing the pollution to the environment.Therefore,calcium carbide chemistry has great application prospect in organic synthesis and chemical production.Propargyl tertiary alcohol is an unsaturated alcohol compound,which is an important intermediate in organic synthesis because of its active chemical properties.The propargyl tertiary alcohol can be used as a raw material to synthesize various heterocyclic skeleton compounds with important values in the fields of medicine,agronomy and the like.Although the methods for the synthesis of propargyl tertiary alcohols are relatively mature,most of these methods require transition metal catalysts,harsh reaction conditions,complex reaction systems and difficult post-treatment operations.Therefore,it is of great significance to explore the synthesis of propargyl tertiary alcohols directly using calcium carbide as a solid alkyne source.The compound containing pyrimidine-2-amine heterocycle has important application value in the aspects of clinical treatment,pesticide and the like because of their antitumor,antifungal,antimalarial and other pharmacological activities.The synthetic methods of pyrimidine-2-amines have been reported for a long time,but the reported methods have some shortcomings,such as narrow range of reaction substrates,difficult preparation of substrates,complicated reaction steps and so on.Therefore,it is still necessary to develop simple and green synthetic methods.This thesis mainly includes:1)using calcium carbide as the solid alkyne source,various 2-oxoacetamides as the starting materials to synthesize the multifunctional compound containing propargyl tertiary alcohol structure,2-hydroxybut-3-yneamides,under mild conditions;2)using divinylketones and guanidine hydrochloride as the starting materials to synthesize 2-amino-4-aryl-6-styrenylpyrimidines under alkaline conditions.This thesis consists of the following three parts:Part I:The research progress in the synthesis of terminal alkynes or internal alkynes,the vinylation of X-H（X=N,O,S）,the additional reactions of unsaturated carbonyl compounds and the cyclization reaction using calcium carbide as an alkyne source,and in the synthesis of pyrimidin-2-amine derivatives are reviewed.Part II:The synthesis of 2-hydroxybut-3-ynamides was studied using calcium carbide as solid alkyne source and 2-oxo-N,2-diarylacetamides as atarting materials.All the compounds were confirmed by ¹H NMR,¹³C NMR and ¹⁹F NMR,and HRMS analyses.This protocol has the most outstanding advantages of using a solid alkyne source with low cost and easy operation,wide reaction substrate range,mild reaction conditions,high yield,and no need of transition metal catalysts in the reaction system.Part III:The synthesis of 2-amino-4-aryl-6-styrenyl pyrimidines was studied using diarylvinyl ketones and guanidine hydrochloride under alkaline conditions.All the compounds were confirmed by ¹H NMR,¹³C NMR and ¹⁹F NMR,and HRMS analyses.The synthetic method has the characteristics of readily available raw materials,wide substrate scope,mild reaction conditions,high yield,and simple operation.