Week 7: New addition and dehydration reactions

This week the focus was on trying addition reactions in order to move the current product closer to one of our goal molecules. The first two reactions were run next to each other. One was a grignard addition using isopropyl magnesium chloride and then other was an organolithium reaction using n-butylithium. The grignard, which had been run once before on a smaller scale, was run using ether as the solvent instead of dichloromethane. This reaction did not actually occur on the larger scale and we think it is because the solvent could not get the starting material completely in solution. However, all the starting material was recollected so nothing was lost from this trial.

The other reaction with n-butylithium worked well for a first trial, producing a 48% pure yield. The reaction was run on a relatively small scale so we wanted to scale up. In order to do this, we needed to run the second aldol condensation again. This time we added more equivalents of the benzaldehyde in the hopes of making up for the amount that has degraded. This reaction produced a 71% yield which was much higher than the previous run. Using this material, we ran the reaction with n-butylithium again and collected a 64% yield. Each time a reaction is run, something new is learned to improve the yield the next time and this was apparent in both the condensation and addition reaction.

week 7

The subsequent reactions were done with two different conditions with the hopes of dehydrating the addition product. This sequence is displayed in the figure above where the first reaction is the addition with the n-butylithium and the second is the dehydration. First, an acid catalyzed dehydration was run using methanesulfonic acid. This is a strong acid that we were hoping would be able to carry out the removal of the hydroxyl group. This reaction did not work as we were hoping it would because the butyl group looks still intact on the NMR spectrum. Next we tried a base catalyzed elimination using methanesulfonyl chloride. This base would make the hydroxyl into a better leaving group and then eliminate it off. However, this reaction did not work as planned. Multiple product were produced so the NMR spectrum was difficult to interpret but we do not believe the desired product was produced. The route that we have been using seems to have hit a dead end after the n-butylithium addition so next week I am planning to move a few steps back and try some new procedures. I have two more weeks of research this summer to move forward and then I will continue again moving product forward in the fall.

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