Green Cyanation Of Halogenated Aromatics Catalyzed By Supported Pd Complexes

Aryl nitriles are a very important class of organic compounds as integral parts of dyes,herbicides,agrochemicals,pharmaceuticals,and natural products.Aryl nitriles have a wide range of applications in organic synthesis as versatile intermediates for the preparation of aldehydes,oximes,amides,carboxylic acids,amines and tetrazole.Therefore,the preparation of aryl nitriles plays an extremely important role in organic synthesis.At present,aryl nitriles are mostly prepared by the cyanation reaction of aryl halides.Traditional cyanation reagents?CuCN,NaCN,KCN,etc.?used for the cyanation reaction of aryl halides have disadvantages such as high toxicity and high risk.The green,non-toxic and cheap cyanide reagent potassium ferrocyanide?K₄[Fe?CN?₆]·3H₂O?has the characteristics of being easily soluble in water and insoluble in less polar organic solvents.As a cyanogen source,it is often necessary to use a high-boiling,highly polar organic solvent,which is difficult to post-treatment.Cyanation catalyzed by Pd complexes has the characteristics of high catalytic activity and mild reaction conditions,but there is the problem that Pd metal is expensive and difficult to separate and recycle.However,there is a problem that Pd metal is expensive and difficult to separate and recycle.Therefore,the development of an efficient,environmentally friendly cyanide reaction system using green non-toxic cyanogen sources and low-boiling organic solvents and capable of achieving the recycling of precious metal catalysts is of significance for theoretical study and practical use.Based on this,this paper developed a green cyanation reaction system using potassium ferrocyanide as cyanogen source,water-toluene two-phase solvent and polyethylene glycol?PEG?-supported Pd as catalyst.The main contents are as follows:A series of PEG-supported phosphine ligands were designed and synthesized.And the PEG-supported phosphine ligands was reacted with Pd?OAc?₂ in situ to form a catalyst,and was subsequently used in a toluene-water two-phase cyanation reaction system in which K₄[Fe?CN?₆]·3H₂O was a cyanogen source.Bromobenzene is selected as a template substrate for cyanation reactions.The effects of factors such as Pd source,ligand,and base on the reaction were investigated.The optimum reaction conditions are as follows:1 mol%Pd?OAc?₂,L/Pd=4/1,30 mol%K₄[Fe?CN?₆]·3H₂O,20 mol%DBU,4 m L water and toluene?v/v=1/1?,0.5 mL Acetonitrile and 100?L iPrOH were added.The reaction temperature was 110°C and the reaction time was 3 h.Under the optimum reaction conditions,the conversion of bromobenzene was up to100%,and the yield of benzonitrile reached was up to 82%.The PEG-supported Pd-catalyst can be reused two times.In the third run,the catalytic activity significantly decreased.The cyanation reaction of a variety of aryl bromide substrates was investigated under the optimum reaction conditions.The yield was 18%-97%,demonstrating that that the catalyst system has good substrate applicability.The results show that the catalytic reaction system has a good catalytic effect on substrates bearing electron-withdrawing groups on the benzene ring with the yield was 57%-97%.If the The substrates bearing electron-donating groups on the benzene ring such as amino groups,hydroxyl groups,etc.,the reaction activity is poor or even no reaction occurs.The mechanism studies show that the reaction was a heterogeneous catalytic reaction,and the cyanation reaction occurred in the organic phase.The PEG carrier played a key role in the catalytic system.The PEG carrier of the Pd catalyst has a phase transfer function and can transfer CN^-from the aqueous phase to the organic phase,thereby realizing a simple,mild and efficient cyanation reaction.The two-phase catalytic cyanide reaction system of aryl halides developed in this paper has the characteristics of high catalytic activity,low catalyst dosage and mild reaction conditions.At the same time,this catalyst system has the advantages of catalyst recycling and reuse.This research provides theoretical research and experimental basis for the practical application of green cyanation reaction.