Construction Of The Micellar Catalytic System Of Polyether-based Surfactants And Its Application For C-S Coupling Reactions In Water

As a safe,stable and low-cost reaction medium,water is considered a green substitute for organic solvents.Micellar catalysis provides an important way to develop aqueous reaction system which can replace organic solvents.Although there have been some important breakthroughs in micellar catalysis,the complicated synthesis and purification process of surfactants and the addition of toxic ligands are still inevitable.Therefore,the design of green,efficient and degradable surfactants with ligand functions has always attracted researcher’s attention.In this paper,different types of surfactants with ligand function were screened and prepared,which can form micellar nanoreactors by self-assemblying in water to analyze the interaction between surfactants and metals,to reveal the influence of molecular structure on the catalytic effect,and to realize the efficient construction of C-S coupling in aqueous phase.The main research contents are as follows:Firstly,by screening a series of commercial non-ionic surfactants,it was found that the amino-terminated polyether surfactant M2070 micelle system could be applied to the Ullmann C-S coupling reaction efficiently.The optimal reaction conditions were as follows:Cu Br（10mol%）as catalyst,M2070 aqueous solution(0.01 mol·L^-1)as solvent,at 100 ^oC for 7 h,the yield up to 90%.A further study on the substrate scope was carried out under the optimal reaction conditions,which proved that M2070 micelle system had good substrate applicability.Solution performance studies showed that the micellar shapes of 0.01 mol·L^-1 M2070 were spherical with an average particle size of 5.08 nm at 100 ^oC,while the average particle size of metal micelles formed by M2070 chelated copper was 6.28 nm.By the characterization of FT-IR,XPS,EDS,it was proved that the free electron pair on amino N atom of M2070 can coordinate with copper ions to form metal micelles with high catalytic activity,thus achieving the reaction system without additional ligands.Then,the solubilization effect of the micellar system on non-polar substrates was proved by DLS experiments.The mechanism can be inferred as follows:surfactant M2070 coordinated the copper which was chelated on the amino group of the palisade area.Iodobenzene dissolving in the hydrophobic core of the micelle was contacted with the hydrophilic nucleophile through the copper salt catalyst of the palisade area,and the aryl sulfone product was released through oxidative addition and reduction.Due to the weak coordination effect between M2070 amino group and copper,the catalytic activity was limited.Therefore,a series of glycosyl surfactants were prepared by modifying M2070 with glycosyl ring as hydrophilic head group,and introduced schiff or amide structures.In addition,nano-copper was prepared in situ by the reductivity of sugar group to realize the synergistic catalysis between micellar nanoreactors and metal nanoparticles in Ullmann C-S coupling reaction.The optimal reaction conditions were selected as follows:Cu（OAc）₂（3 mol%）as catalyst,Glu M aqueous solution(0.005 mol·L^-1)as solvent,at 100 ^oC for 7 h,the yield up to 92%.Substrate expansion proved that the system had wide applicability,and can be extended to the synthesis of the drug Zolimidine in aqueous phase.By the characterization of in-situ IR,TEM,HR-TEM,XRD and XPS,it was proved that the glucose-modified amino-terminated polyether surfactant Glu M can solubilize hydrophobic substrate.Schiff base in its structure had intensive chelating metal ability,which can form stable coordination bond with copper.Morever,the reduction of the sugar group can in situ generate Cu₂O particles with an average particle size of 1.35 nm.The copper nanoparticles were transferred to the surface of the micellar nanoreactor through the“Nano to Nano”effect,and then synergically catalyzed the Ulmann C-S coupling reaction.Finally,the economical and environmentally friendly elemental sulfur（S₈）was used as sulfur source.The copper-catalyzed synthesis of C-3 thioether indole with indole,iodobenzene and sulfur was studied in micellar system.With 0.005 mol·L^-1 Glu M aqueous solution as the solvent,Cu SO₄ as the catalyst,K₂CO₃ as the base,1,10-phenanthroline as the ligand,at 100°C for 12 h,the yield up to 85%.The substrate expansion under the optimized reaction conditions proved that the reaction system had good substrate applicability.Combined with the verification experiment and DFT theoretical calculation,the free radical mechanism of indole,iodobenzene and sulfur coupling reaction in micellar medium was confirmed.The mechanism can be inferred as follows:K₂CO₃ can promote the coupling of iodobenzene and elomeric sulfur to form the intermediate diphenyldithioether,and diphenyldithioether generated Ph S·radical under the action of copper and1,10-phenanthroline.Ph S·interacted with the copper complex formed by 1,10-phenanthroline and Glu M,and then reacted with indole to form the C-3 substituted thioether indole.