Application Of Abietic Surfactant In Synthesis Of Ynamides In Water

Due to its unique reactivity,ynamides have become versatile intermediates and precursors in organic synthesis.In recent years,there are many methods to synthesize ynamides,but in harsh reaction conditions.Water is the best solvent because it is abundant,low-price,non-toxic,non-flammable and renewable.Accordingly,it is of great significance to develop an environmentally friendly and sustainable method for synthesizing ynaimdes in water.In the first part,abietic acid was used as raw material to obtain abietic alcohol by reduction.Subsequent esterification provided abietic succinate.Finally,surfactant APGS-550-M was synthesized by the reaction of abietic succinate and polyethylene glycol monomethyl ether 550.Its structure was determined by ¹H NMR and ¹³C NMR.In 2 wt%APGS-550-M/H₂O,benzyl-4-methylbenzenesulfonamide and 1-bromoacetylene-4-tert-butyl-benzene were used as model substrates.The reaction reacted smoothly at 50?for 26 hours to form the ynamide in88%HPLC yield,using 10 mol%CuSO₄·5H₂O as catalyst?10 mol%?,20 mol%1,10-phenanthroline as ligand and 2 equivalents of K₂CO₃ as base.The optimal reaction conditions were determined by screening solvents,copper catalysts and ligands.Under the optimal reaction conditions,different nitrogen-containing nucleophilic reagents and alkynyl bromides were examined and the structures of ynamides were determined by ¹H NMR?¹³C NMR and HMRS-ESI.The necessity of copper catalyst,ligand and base in the reaction conditions was studied by control experiments.Using?bromoacetylene?benzene and benzyl-4-methylbenzene-sulfonamide as substrates,the gram-scale experiment was carried out and the yield was 92%.In the second part,natural products estrone and sitosterol were modified in 2 wt%APGS-550-M/H₂O.Firstly,estrone ethynyl bromide and sitosterol ethynyl bromide were synthesized.Next,the desired products were obtained by reacting these two raw materials with benzyl-4-methylbenzenesulfonamide respectively.The structures of these products were determined by ¹H NMR?¹³C NMR and HRMS-ESI.In the third part,the“in-flask”recycling experiments were carried out to show that the aqueous APGS-550-M solution can be reused for up to three recycles.Finally,the E factor was calculated,and the value was quite low,demonstrating the greenness of the reaction.