Study On The Coupling Reaction Of Biphenyl Tosylhydrazones For C-X Bonds Formation

In recent decades,transition metal catalyzed coupling reactions have been one of the most effective methods for constructing C-X(X = C,O,N,etc.)bonds,and are widely used in functional drugs,optoelectronic materials,thermal recording materials,dyes,as well as the synthesis of household chemical products.On the basis of this work,transition metal catalyzed coupling reactions(eg,Suzuki,Ullmann,Glaser,etc.)have been developed and applied widely.However,the development of more efficient,green catalytic system to build C-X bonds is still a hotspot in organic synthesis.In this paper,biphenyl carbonyl compounds were prepared by Pd-catalyzed Suzuki coupling reaction of bromoacetophenone(or p-bromobenzaldehyde)and aryl boronic acids,and the corresponding biphenyl N-tosylhydrazones were prepared were prepared by the reaction of biphenyl carbonyl compounds and p-toluenesulfonhydrazide.The main contents of this thesis include the following three parts:First,the reductive coupling of biphenyl-4-carbonyl compounds derived from tosylhydrazones with phenols or benzyl alcohols under metal-free reaction conditions is described.Various 4-benzyl biphenyl ether compounds,representing an important structural element in organic synthesis,could be obtained in 38-83% yields by using K2CO3 as base,toluene as solvent,at 110 °C for 24 h.The synthesis was performed on a gram-scale to verify the applicability of this synthetic method.The reaction was performed using 1.83 g(5.0 mmol)of biphenyl tosylhydrazone 3a and 1.60 g(17.0 mmol)of phenol.Fortunately,the reaction proceeded smoothly with a product yield of 78%,resulting in the production of 1.07 g of the desired product.Importantly,the catalytic system presented here enables the use of easily accessible starting materials and may be employed on a wide variety of substrates with good functional group tolerance.Secondly,a series of new 4-(1-azidoethyl)-1,1'-biphenyl derivatives were synthesized in 34-74% yields by the metal-free reductive reactions of biphenyl tosylhydrazones and sodium azide,K2CO3 as base,tetrabutyl ammonium bromide as phase transfer Catalyst,toluene as solvent,at 130 °C for 29 h.The resulting biphenyl derivatives were further reacted with aryl acetylenes to afford novel 1,4-substituted 1,2,3-triazoles in 27-94% yields by water-soluble salen-Cu(II)catalyzed azide–alkyne cycloaddition in water at 70 °C for 7 h in the absence of any organic solvent or phase transfer agent.Moreover,the catalytic system exhibited wide substrate scope and high functional-group tolerances.Thirdly,synthesis of di-substituted aryl olefins via a Pd(0)-catalyzed cross-coupling reaction of biphenyl ketones/aldehydes,tosylhydrazide,and aryl bromides(or benzyl halides)was developed.We found the following combination to be the most suitable reaction conditions: 4-acetylbiphenyl(0.5 mmol),p-toluenesulfonyl hydrazide(0.55 mmol),1-bromo-4-methylbenzene(1.0 mmol),Pd(PPh3)4(5 mol%),and LiOtBu(1.0 mmol)at T1 = 100 °C(t1 = 2 h)and T2 = 100 °C(t2 = 12 h)in 1,4-dioxane(3 mL)in a nitrogen atmosphere.Upon optimizing the reaction conditions,we further investigated the substrate scope of this one-pot two-step coupling reaction,and the corresponding 1,1-diaryl substituted olefins products were obtained in 23-96% yields.We then used biphenyl formaldehyde and benzyl bromides as coupling partners in the one-pot two-step transformation.The desired 1,2-diaryl substituted olefins products were obtained in 37-85% yields.This methodology was achieved by one-pot two-step reactions involving the preparation of N-tosylhydrazones by reacting tosylhydrazide with biphenyl ketones/aldehydes,followed by coupling with aryl bromides(or benzyl halides)in the presence of Pd(PPh3)4 and lithium t-butoxide to produce various di-substituted aryl olefins.