Construction Of Aqueous Reaction System Based On Sugar-base Compounds And Its Application In Copper-catalyzed Ullmann Reactions

The construction of C-X bonds is widely used in biology,medicine and material chemistry.Copper catalyzed Ullmann reaction is one of the common methods to construct C-X bonds.The early Ullmann reaction required high temperature,strong base,a large amount of copper and organic solvents,which limited its wide application.Using water as reaction medium instead of traditional organic solvents has always been a hot topic in fine chemistry research.But,the solubility of most organic substrates and catalysts in water is poor,which affects the mass transfer and diffusion in the reaction process,and limits water to become a common green reaction medium.To solve this problem,this paper proposes two solutions:one is to prepare nano catalyst to provide high catalytic activity;The other is to prepare surfactants using glycosyl compounds to solubilize organic substrates and promote organic reactions.Firstly,three kinds of ionic surfactants（LA12,LA14 and LA16）and two kinds of non-ionic surfactants（ALA12 and ALA14）were synthesized by using sugar-based compounds（lactonic acid or lactose）as hydrophilic materials and alkyl amines as hydrophobic materials.These sugar-based surfactants were used to prepare nano copper catalysts,which successfully catalyzed Ullmann C-S coupling reactions in water.The optimum conditions for this coupling reactions could be concluded:Cu/ALA14-A as the catalyst,100℃as the reaction temperature.The highest yield of C-S coupling model reaction was 86%.The copper nanoparticles were about 5.02 nm,which were spherical and had good dispersion.The substrate expansion experiments show that the catalytic system has a wide range of applicability.The reaction system can make the Ullmann C-S reaction proceed efficiently in pure water without additional ligands.The optimum conditions for this coupling reactions could be concluded:Cu/ALA14-A as the catalyst,100℃as the reaction temperature.After 12 hours,the highest yield of model C-S was 86%.TEM and HR-TEM showed that the copper nanoparticles were spherical particles with a diameter of about 5.02nm and had good dispersion.The substrate expansion experiments showed that the catalytic system had a wide range of applicability.The reaction system could catalyze Ullmann coupling reactions effectively in water without additional ligands.The Cu/ALA14-A catalyst system didn’t need organic solvents as the reaction medium for coupling reaction,but organic solvents were used in the preparation of the catalyst.Therefore,using sugar-based compounds（gum arabic and chitosan）as protective agents,a series of nano-copper catalysts were synthesized in aqueous solution by chemical reduction method and catalyzed the Ullmann C-N coupling reaction.The optimum conditions for this coupling reactions could be concluded:Cu-GA@CS₂₅ as the catalyst,110℃as the reaction temperature,and Na₂CO₃ as the base,the yield up to 92%after the reaction carried out in H₂O/DMSO for 12 hours.The preparation conditions of Cu-GA@CS₂₅ were as follows:under the joint action of gum arabic and chitosan,the copper source Cu SO₄·5H₂O was reduced by hydrazine hydrate solution at 25℃.A series of characterizations（such as TEM,XRD,HR-TEM）were used to characterize Cu-GA@CS₂₅.The results showed that the obtained Cu NPs were spherical particles of about 5.15 nm and Cu（0）nanoparticles with good crystallinity and high purity.The results showed that the obtained nanoparticles were zero valent copper particles with spherical shape of about 5.15 nm.Moreover,they had good crystallinity and high purity.The preparation of Cu-GA@CS₂₅ required the addition of toxic and explosive hydrazine hydrate as reducing agent.The specific strategy was as follows:N-dodecyl glucosamine(D₁₂Ga)was synthesized from glucose as hydrophilic raw material and dodecylamine as hydrophobic raw material,then these Gemini surfactants(C_nD₁₂)were constructed by using dicarboxylic acid linked D₁₂Ga.The C₁₁D₁₂ aqueous solution had special phase behavior,so a series of characterization and study had been carried out on it.It was verified that the transition of aggregates from the spherical micelles to vesicles was induced by increasing the temperature.Moreover,further increasing temperature caused the decrease of vesicle size.Compared with common commercial surfactants,sugar based surfactants had obvious advantages in Ullmann C-S reaction.The yield of 95%could be obtained by using C₁₁D₁₂aqueous solution as reaction medium and Cu Br as catalyst at 100℃for 12h.The experimental results showed that the reaction system had good substrate applicability and recyclability.Based on the verification experiment and theoretical calculation,the possible catalytic mechanism were:Cu Br was chelated by hydrophilic glycosyl,aryl halides was solubilized by the bilayer of vesicles,arylsulfinates was enriched around the cationic vesicles by electrostatic attraction,and the reaction took place on the surface of the bilayer of vesicles.