Copper-Free Sonogashira Coupling To Access Ynamides In Aqueous Solution

Metal organic chemistry is a discipline that intersects organic chemistry and inorganic chemistry.After years of development,it has become an important part of modern synthetic chemistry.The Sonogashira coupling reaction is a sp-sp2 carbon cross-coupling reaction between a terminal alkyne and an aryl(alkenyl)group halide catalyzed by a Pd/Cu catalytic system to construct a new carbon-carbon bond reaction.The reaction was further studied by Sonogashira et al.on the basis of previous work,and has been in development for forty-four years.At present,the Sonogashira coupling reaction is relatively mature and is one of the most widely used human name reactions.From the end of the 20 th century,people realized that industrial production is increasingly polluting the environment.Therefore,the concept of green chemistry was put forward.The use of chemical reactions to reduce or even eliminate the burden on the environment is an important direction for chemical research in the 21 st century.It has been thirty-five years since the concept of green chemistry was put forward.Although we have initially realized green chemistry,there is still a long way to go to develop green chemistry.In this paper,we mainly study the synthesis of internal acetyleneamine in the copper phase-free sonoshiashira coupling reaction in the aqueous phase.In the acetylide compound,the nitrogen atom imparts an electron to the carbon-carbon triple bond,and the electron-withdrawing group(EWG)attached to the nitrogen atom stabilizes the alkynamine compound.Therefore,in general,the alkynamide compound is stable to air..Alkynamides are generally prepared by three methods:hydrogen halide elimination,Witulski rearrangement,and Ullmann coupling.In this paper,we first realized the use of the cationic surfactant cetyltrimethylammonium bromide as an intermediate carrier(500 g for 200 g),and the acetylenic amide in copper-free catalyzed Sonogashira couple in deionized water.In combination with alkyneamine,34 examples were successfully achieved with a yield of 16-96% yield.In the reaction system,it is not necessary to add a nano catalyst,the reaction raw material is simple and easy,the price is reasonable,and the operation steps are relatively simple,and a synthesis method for realizing large-scale preparation of the internal acetylene amide is expected.This method can modify natural complex products.For example,we have obtained an internal propargylamine of dehydrofungamide in excellent yield.Dehydroabietylamine is extracted from rosin.And recycling of cetyltrimethylammonium bromide is achieved.It can be recycled six times with a yield of 70%,and can be recycled eight times with a yield of 50%.In industrial production,a relatively stable high yield can also be achieved by adding a portion of cetyltrimethylammonium bromide during the cycle.Hydrolysis of the alkynamide can be reduced under acidic conditions.The olefination of the terminal alkynamide can be achieved without using palladium as a catalyst and using copper as a catalyst.