[voidSetup]

I'm going to run a reaction using a terminal alkyne to alkylate a primary halide, and I'm wondering if anyone has tips on the conditions.  I'm going to dissolve the alkyne in THF, and slowly add n-BuLi as my base.  I've heard of using HMPA or DMPU as a cosolvent, so should I add that in with the alkyne, or maybe dissolve my primary halide in it?  Will the yield be decent without it?  Any other ideas would be appreciated.

[hypervalent_iodine]

I would use DMPU over HMPA. It's less toxic and can sometimes give better yields and regioselectivity.You add it as a cosolvent with your alkyne/THF solution. I don't remember the ratio - something like 1:2 DMPU:THF from memory. You could dissolve your halide in a small amount of it as well for when you add it in (I recommend adding by cannula).

You might not even need to worry about it though. If you keep the temperature low enough, regioselectivity shouldn't be an issue, especially if you're using highly reactive halides. In my experience, deprotonation is best done at -78oC. The addition of your halide tends to be where most of the problems occur in these reactions. You may not be able to add it at -78oC (the reaction might freeze, for instance), in which case I would add dropwise via cannula addition at -50oC or -30oC and monitor it closely with TLC. Sometimes it's also a good idea to have the halide solution chilled as well.

Most importantly though - make sure everything is as dry as dry can be. As well, you'd be surprised how much fresh distilled reagents can make a difference to your yields, so perhaps look into that.

[voidSetup]

Thanks for the feedback.  So do I add the DMPU after the deprotonation or before I add the n-BuLi?  I can look into distilling the alkyne, but the halide is an oil from a previous step (i'm guessing BP around 170-200C), so I'm not sure about that.  It shouldn't be very hygroscopic though.  We have a KF titrator in the lab so I can test my materials for water.

I'll try doing the deprotonation at -78C then, and I was thinking about adding the halide with a gastight syrine, possibly with a syringe pump so I can try different rates of addition.  Do you think the cannula is a better idea?  Also, if the reaction mixture does freeze, can I just warm it up and continue on or is it going to ruin it?

[hypervalent_iodine]

Probably add it after the deprotonation. I would still try and distill both of you reagents. If you have a Kugelrohr, you could distil the halide with that.

Yes, a syringe pump works just as well provided your halide isn't particularly nasty an can be easy cleaned. The ones I work with are all potent lachrymatory agents that are incredibly hard to clean off. I try to avoid putting it near anything that isn't disposable or can't be subjected to high temperature (for cleaning).

If the reaction freezes, you'll need to pull it out of the acetone/dry ice bath and let it warm until it melts, but try not to let it warm to rt. I would have a -30oC or -20oC bath handy, or perhaps just an ice bath that you can use to swap it into should the -78oC fail.

[voidSetup]

Ok sounds good.  I don't think we have a Kugelrohr.  I work in an analytical lab, but I'm just doing some synthesis in my free time.  The organic chemists probably have one but I'm not sure.  I'll probably order my solvents in sealed bottles over sieves, and just transfer them via syringe or cannula so they should be dry.

I don't think my halide should be too nasty or difficult to clean.  It's just 10-bromo-decanol with the alcohol protected as THP.  I'll probably give it a go next week.  Thanks!

[hypervalent_iodine]

No problems.

Oh, though it's probably a fairly obvious thing to do, I thought I'd mention that if the deprotonation is too slow at -78oC, try warming it a bit to -50oC. An internal thermometer would certainly not go astray in this kind of reaction.

[voidSetup]

How can I tell when the deprotonation is complete?  Oh yea, and should the alkyne or the base be the limiting reagent?

[voidSetup]

So I just received my alkyne and was looking at the MSDS.  The melting point is -19C, so will the solution freeze if I try the deprotonation at -50C or should I be ok?

[discodermolide]

So I just received my alkyne and was looking at the MSDS.  The melting point is -19C, so will the solution freeze if I try the deprotonation at -50C or should I be ok?

No it won't freeze in THF solution.
It may be better to use sodium amide as the base,

[orgopete]

It may be better to use sodium amide as the base,

If you have a time machine and it is set for 1952.

Methyl or butyllithium should be fine depending on functional groups. You could use LDA, but I cannot think of any reason I would prefer sodamide. (I'm talking lab scale.)

[discodermolide]

It may be better to use sodium amide as the base,

If you have a time machine and it is set for 1952.

Methyl or butyllithium should be fine depending on functional groups. You could use LDA, but I cannot think of any reason I would prefer sodamide. (I'm talking lab scale.)

According to my books and practical experience sodamide is the base of choice for the deprotonation of terminal acetylenes. You have to be careful with the choice of base and the temperature otherwise the acetylene will start to polymerize on you.

[voidSetup]

There are no other functional groups on the alkyne that the base could react with. How can it polymerize?

Thanks for the advice, I'll give it a go this week.

[discodermolide]

There are no other functional groups on the alkyne that the base could react with. How can it polymerize?

Thanks for the advice, I'll give it a go this week.

I did not mean the base but the acetylene anion.
Forgive me but I am not a mind reader and do not know what other functionality your molecule has, you did not see fit to communicate this.
Sodium amide is very much in use in the 21st century, and I would really advise that you use that base.