Sequential Sonogashira And Glaser Coupling Reaction Based Synthesis Of Diarylbutadiynes

Of many transition-metal catalyzed coupling reactions Sonogashira coupling and Glaser coupling attract great attention because they can be used for the synthesis of alkynes and diynes. The Sonogashira coupling catalyzed with Pd/Cu and the Glaser coupling with Cu complex are both easy to operate and the reactions condition are mild, both of them are the key methods for the synthesis of alkynes.The main research contents of this paper are the sequential coupling reactions with silicon-protected alkynes and aryl bromide as reactants to establish the symmetrical 1,4-disubstituted-1,3-butadiynes efficiently. Specific summarized as the following two parts:We connected normal Sonogashira coupling with Glaser coupling reaction, with Cul and PdCl2(PPh3)2 as catalysts, from aryl bromide to synthesize 1,3-butadiynes. Followed by the Sonogashira coupling reaction, we remove the metal catalysts by filtration, then NaOH and CH3CN were added into the crude product directly at 60? for several hours to give diarylbutadiynes.1. The Glaser coupling reaction was optimized by screening different reaction conditions, including, the amount of NaOH, solvent and temperature. The optimal condition is: at 60?,2 eq. NaOH was added into the crude product of Sonogashira coupling reaction, with CH3CN as solvent. Using the optimized conditions, the substrate scope was investigated with the series of benzene, heterocyclic aromatic and polycyclic aromatic hydrocarbon. The electron-donating functional group (-CH3,-OH,-OCH3) and electron-withdrawing group (-F,-CHO,-COOH,-NO2) were chosen as substituent to expand the substrate types. The advantages of this method are easy, mild and broad substrates tolerance. The result demonstrate that the substrates with electron-donating group provide high yields in less time. While for the substrates with a nitrogen atom, it is difficult to get the target molecule.2. The control experiments were carried out to test the influence of the amount of catalysts. By removing the solvent after the Sonogashira reactionwhile keeping the catalysts intact for continued use in the next Glaser reaction, we found that the yields were found to be improved by 14-21%. This indicates that the increased catalyst loading has an effect on the Glaser coupling reaction, but the amount of Pd and Cu catalysts needed are substantially higher compared with the amount used for filtration. Although there are still Pd/Cu residual in the second step, the amount of Pd/Cu are 1/55 and 1/40 compared with the solution before filtration. This shows that trace metal catalysts can also catalyse the reaction efficiently.