Synthesis Of Pyrazoles And Fused Pyridines Through The Reaction Of Propargyl Alcohols

Domino reactions have become a hot topic in the field of organic chemistry research in recent years.It is one of the effective methods to access many different complex organic compounds.Therefore,domino reaction has been widely used in the synthesis of organic compounds,especially in the construction of some natural products In this dissertation,three kinds of aza-heterocycles were synthesized through domino reaction of propargyl alcohols.During these processes,the combination of the catalytic performance of Br?nsted acid with microwave heating makes reaction substrates maximally convert into the desired molecules while avoiding the isolation of intermediates,thereby improving the atom efficiency and lowering emissions of waste.Therefore,these reaction feature the high efficiency and environmental friendliness in the modern chemistry.The contents of this dissertation are summarized as follows:In the first part,the application of propargyl alcohols as effective synthons in the construction of aza-heterocyclic skeletons is described.On the basis of describtion of previous propargyl alcohols-invovled domino reaction,the selection basis and novelty are put forward in this dissertation.In the second part,a new microwave-assisted synthesis of pyrazoles was developed though domino reaction of propargyl alcohols.By using structurally diverse propargyl alcohols and aryl hydrazine as the starting materials,the reaction was carried out in HOAc under microwave heating,enabling dehydroxylated [3+2] cyclization to regioselectively synthesize a series of functionalized pyrazole derivatives with good to excellent yields.During the reaction process,it was found that when electron-donating groups resided in the aromatic ring of aryl hydrazines favors the reaction process to give a higher yield of the desried products whereas electron-withdrawing counterparts decreased the reaction efficiency.In addition,substituents with electron-donating groups on the benzene ring of the propargyl alcohols are benifical to the conversion and provided the higher yields of the desired products as compared with electron-withdrawing group.Based on the literature reports,a possible reaction mechanismwas proposed.In the third part,a new dehydroxylated [3+3] cyclization reaction between propargyl alcohols and enaminones was describes.The reaction of the preformed cyclic enaminones bearing 1,3-binucleophilic sites with propargyl alcohols having 1,3-electrophilic centers was conducted under microwave irradiation,regioselectively affording polysubstituted hydroquinolines with good to excellent yields.The reaction proceeded sommthly in HOAc by using p-toluenesulfonic acid(p-TsOH)as a Br?nsted acid promotor.To further extend the scope of this reaction,tetronic acid-derived enamine ester as a replacement of enamineones was subjected with propargyl alcohols under microwave heating.The reaction could proceed smoothly,providing the corresponding hydrofuro[3,4-b]pyridines with good yield.The reaction has the advantages of easy availability of starting materials,broad substrate scope,mild reaction conditions and short reaction time,which provides a new rapid and effective method for the synthesis of these fused pyridinesIn the fourth part,a new [3+3] cyclization of propargyl alcohols with 5-aminopyrazoles was reproted.A series of pyrazolo[3,4-b]pyridine derivatives were efficiently synthesized by the two-component domimo reaction of propargyl alcohols with cheap and readily available 5-aminopyrazoles as 1,3-binucleophiles.During this reaction process,the hydroxyl group of the propargyl alcohols was activated by Br?nsted acid,making the propargyl alcohols convert into allene cation through dehydroxylation,followed by nucleophilic addition with 5-aminopyrazoles and subsequent cyclization to the target products.The above described three types of reactions feature a short reaction time,simple operation and high yields without purification of intermediates.The functional pyrazoles,furo[3,4-b]pyridines and pyrazolo[3,4-b]pyridine derivatives were respectively synthesized by using propargyl alcohols as the key reaction substrate.The structures of the resultant compounds were confirmed by NMR,IR and HRMS,some of which was further confirmed by X-single crystal analysis.