Synthesis Of1,3,4-Trisubstituted Pyrazoles From A-(1,3-Thiazoi-2-yl) Enamine Ketones Via [4+1] Cyclization

Transition metal-catalyzed coupling reactions, such as carbon-carbon coupling,carbon-nitrogen coupling and nitrogen-nitrogen coupling, have been a hot topic oforganic synthetic chemistry. Palladium, nickel, copper, iron, rubidium, etc. have beenwidely used in this type of reactions. Reports of new synthetic methods ofnitrogen-containing heterocyclic compounds published frequently, most of which haverelationship with coupling reactions.As a catalyst, Copper has the advantages of easypreparation, low cost, low toxicity and high stability. Reactions catalyzed by copperusually have mild conditions, simple processes and high selectivities.Pyrazole is an important nitrogen-containing heterocyclic compound with a cutestructure. But with different substituents at different positions, pyrazole derivatives canhave a variety of pharmacological activities. For example, substituted pyrazoles can beused as oxygenase-2inhibitors, protein kinase inhibitors and HIV-1reverse transcriptaseinhibitors. Furthermore, some substituted pyrazole compounds can act as ligands ofcoupling reactions, others may have liquid crystal properties. How to synthesize specificsubstituted pyrazoles with high selectivities, is the key direction of pyrazole synthesis.Methods with transition metal-catalyzed cross-coupling reactions, have attracted theattention of researchers.On the other hand, with a variety of functional groups, numerous reaction sites andeasy availabilities,-oxo ketene dithioacetals are important intermediates for modernorganic synthesis chemistry, widely used in medicinal chemistry and materials chemistry.Especially in the last three decades, with test methods diversified and synthetic strategyiesenriched, synthesis methods, structural developments and applications of-oxo ketenedithioacetals in organic synthesis have made tremendous progress.Depending on completed work, three organic reaction intermediates are synthesizedfrom-oxo ketene dithioacetals. This paper focuses on transition metal-catalyzedcarbon-nitrogen coupling and nitrogen-nitrogen coupling reactions between the threekinds of intermediates and amines, and [4+1] cyclocondensations are expected to theformation of substituted pyrazoles. As follows: 1. Depending on completed work,2-(1,3-dithian-2-yl)-3-oxo-N-phenylbutanamide、3-acetyl-4-(phenylamino)but-3-en-2-one and three kinds of-(1,3-thiazol-2-yl) enamineketones are synthesized from five kinds of-oxo ketene dithioacetals,which are used insubsequent experiments as reaction intermediates.2. Explore possibilities of formation of pyrazoles between the three intermediatesand primary amines under different catalysts. Optimize suitable reaction conditions.3. Fiveteen kinds of1,3,4-trisubstituted pyrazoles are achieved via [4+1]cyclo-condensations form copper catalyzes carbon-nitrogen coupling and nitrogen-nitrogen coupling reactions between-(1,3-thiazol-2-yl) enamine ketones and primaryamines.