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Chemistry Forums for Students => Organic Chemistry Forum => Organic Chemistry Forum for Graduate Students and Professionals => Topic started by: baum0372 on November 01, 2013, 12:59:31 PM

Title: Mitsonobu Reaction - Air/Water Sensitive
Post by: baum0372 on November 01, 2013, 12:59:31 PM

I have looked into the literature but I'm having a hard time figuring out whether this is air or water sensitive.  I think that the water should eliminate to form hydrazine or ethanol relatively quickly but I am not sure?

Also, is the addition of reagents important?  I've heard of someone adding the alcohol last who got good results.  Thanks!

Title: Re: Mitsonobu Reaction - Air/Water Sensitive
Post by: Doc Oc on November 08, 2013, 09:02:32 AM

In my experience, you do want to exclude air and water, but you don't need to be particularly rigorous.  No distilling of solvents or blowing nitrogen or argon into the reaction.  The biggest issue I ran into was using old triphenylphosphine, because it oxidizes over time, so you need to add more than you think to compensate.  Incidentally, getting rid of triphenylphosphine oxide is why I hate Mitsunobu (and other TPPO generating) reactions.

Order of addition is important, because you need to activate the DEAD/DIAD/whatever you use.  PPh₃ and azadicarboxylate first, then your substrate, nucleophile goes in last.