[polysci]

What is the typical color of a Mitsunobu reaction using DIAD/Ph3P?  Mine is turning dark orange/red after 24 hours and isn't working and I didn't know if the color was an indication of what was going wrong.

Thanks,

[OC pro]

DIAD comes usually from Aldrich as an orange solution. I always observe that my Mitsunobu´s are orangish to brownish. The colour is no indication whether your reaction works fine or not. Have you done proper TLC control yet?

[polysci]

Yes, I have TLC'd and run a column to separate and identify the individual components.  The two molecules being coupled are a primary alcohol and maleimide (I've read the paper concerning mitsunobu's and maleimide) and maleimide is being consumed whereas all of the primary alcohol is not.  I just wanted to make sure the color change wasn't indicative of poor reaction set up such as the the presence of water reacting with the preformed betaine.  The dark colored component of the reaction also does not travel through silica using 100% EtOAc.  I'm using "anhydrous" methylene chloride but how sensitive is this reaction to water?

Thanks again,

[OC pro]

Not extremely sensitive towards water. Anhydrous dichloromethane is o.k.
Was your DIAD fresh? It decomposes slowly upon storage. I always start with 1.2 equiv. of DIAD and when I feel on TLC the reaction slows down completely I give an extra shot of 0.2equiv.. Yields are always moderate ca. 60-80% in good cases.

[Hand15]

Well mine usually turned from orange to bright yellow~

Maybe you should try changing the order of addition of you reagents. I usually add my alcohol, Nu-H, and PPh3 first and then add DIAD slowly into the solution. If it's not working, try add PPh3 and DIAD first to afford the reactive intermediate, then add the alcohol, and lastly add the Nu-H.