The Effects of Microwave Irradiation on Glaser-Hay Coupling Reactions

I will be producing a small molecule library of small molecules, specifically bisacetylenes, with varying functionalities that will be tested on miRNAs with the hypothesis that they will have some effect of the regulation of miRNA’s.  The misregulation of miRNAs has been attributed to the cause of various cancers and diseases; therefore, being able to fix this misregulation has become a major scientific inquiry in the world of cancer research.

I will be using a glaser-hay coupling reaction to produce the bisacetylenes.  This reaction brings two terminal alkynes together to form cyclic or symmetrical bisacetylenes using a copper-TMEDA complex as a catalyst.  Varying the functionalities of the terminal alkynes, I will be able to make an array of bisacetylenes to be tested on miRNAs.

I will also be running these reactions under microwave irradiation instead of allowing them to take place over a couple of hours, as most glaser-hay coupling reactions are.  This will theoretically increase the yield and decrease the time it takes to to produce the desired bisacetylene.  There is a promising amount of literature that proves the desired function of microwave irradiation; however, I will run a separate reaction in a heat bath at the same temperature and time as the microwave to  prove that microwave irradiation is producing yields of higher quantities than a reaction without it.

Furthermore, in order to isolate a desired product of interest, I will use a solid-phase support to carry out the reaction.  I will first immobilize one terminal alkyne onto a resin and then carry out a regular glaser-hay coupling reaction under microwave irradiation.  The resin can then be washed away, along with unwanted products.

I am in the process of finding ideal reaction conditions (i.e. MW time, MW power, and solution) that will produce the highest yields of bisacetylenes.  I will do this using the reaction with phenyl acetylene to produce diphenylacetylene, without the use of resin since diphenylacetylene will be the only product in this case.  I will hold all variables equal, while testing varying amounts or degrees of the previously stated variables in order to determine reaction conditions that produce the highest yield.

-Ryan Tyler