I am trying to increase the yield for the reaction below. I did the column and I saw that the major side-product is the symmetric dimer formed by 4-bromobenzyl bromide. I imagine that NaH is hydrolyzed and the ions hydroxide (NaOH) eliminate the bromide by SN2, then this molecule does a second SN2 on 4-bromobenzyl bromide.
I ordered a new NaH, however, our glove box is not available at the moment. So, I am trying to find a solution to increase the yield of this reaction and achieve a final synthesis in gram scale.
Aiming to hinder the hydrolysis of NaH, I am purging N2 into the old flask every single time that I need to open the NaH flask, but I am not sure that this technique avoids the salt hydrolysis.
Thank you!
Dear Gabriel Perli the quality of the used sodium hydride can certainly be crucial. Purging the flask containing the NaH certainly makes sense. Don't you have a Schlenk line which you could use instead of working in the dry-box? According to the original procedure, the entire reaction must be carried out under argon using anhydrous THF. Did you make sure that your THF was really dry? By the way, with 45% the yield reported by the authors isn't really very high.
My suggestion would be to use commercially available NaN(SiMe3)2 to deprotonate the starting alcohol. This reagent is not very air-sensitive. You yould also try elemental sodium to do the deprotonation. Then you see the end of the reaction when all the Na has dissolved.
Dear Gabriel Perli the quality of the used sodium hydride can certainly be crucial. Purging the flask containing the NaH certainly makes sense. Don't you have a Schlenk line which you could use instead of working in the dry-box? According to the original procedure, the entire reaction must be carried out under argon using anhydrous THF. Did you make sure that your THF was really dry? By the way, with 45% the yield reported by the authors isn't really very high.
My suggestion would be to use commercially available NaN(SiMe3)2 to deprotonate the starting alcohol. This reagent is not very air-sensitive. You yould also try elemental sodium to do the deprotonation. Then you see the end of the reaction when all the Na has dissolved.
Dear Prof. Frank T. Edelmann , thank you so much for your time replying to this question.
I am already using a Schenk line. Indeed, I did the reaction under argon atmosphere and I do believe that my THF is well dried. The problem could be the NaH.
I appreciated your answer, I will take a look into this base. Your answer made me remember LDA, I have worked with this base once.
Thank you once again Professor!
Dear Gabriel Perli I agree with you in that under these conditions it is quite likely that the NaH caused the problems. Perhaps you can buy a fresh sample of sodium hydride. I'm pretty sure, however, that your starting alcohol can be deprotonated by other strong bases. Personally I would try small pieces of freshly cut sodium.
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