[edlovat]

Hi everyone!

I wanted to ask if someone ever had a similar problem. I am trying to prepare a phosphate from benzoin by adding 1.1 ekv of NaH and after a 30 min at 0° adding 1.1 ekv of diethyl chlorophosphate all in THF. But I have very low yeals - around 20% of monophosphate and 25% of bisphosphate and nothing changes when adding more equivalents of the chlorophosphate. Can it be caused by the insufficient deprotonation?

Thanks for any idea...

[pgk]

Two different phenomena occur simultaneously:
1). Tautomerism to vic-dihydroxystilbene decreases the acidity of α-keto hydroxyl group. Thus, the yield can slightly be increased by longer reaction times. Using another base is not helpful, due to incompatibility with diethyl chlorophosphate.
2). The steric hindrance of the benzene rings dramatically decrease the yield of the reaction. Thus, the yield can slightly be increased by working at higher temperatures (e.g. 5-10oC or possibly, at room temperature) that accelerates the rotation of the C-Φ bonds. Unfortunately, very high temperatures cannot be applied to this kind of reactions.

[clarkstill]

What do you mean by the 'bisphosphate'? Im not sure where the second phosphate is going...do you mean a biphosphate/pyrophosphate?

Also, is the NaH new? It can be horribly contaminated with NaOH if the bottle has been sitting around for a while. Also, it's normally supplied as a 60% dispersion in mineral oil so you need to multiply the equivalence by 5/3 (apologies if you already knew this, just checking!)

I'd try a new pot of NaH and see if it helps.

[rolnor]

Diethylchlorophosphate is fairly reactive, you can not use a milder base like diisopropylethylamine? Maby a catalyst like DMAP?

[edlovat]

What do you mean by the 'bisphosphate'? Im not sure where the second phosphate is going...do you mean a biphosphate/pyrophosphate?

Also, is the NaH new? It can be horribly contaminated with NaOH if the bottle has been sitting around for a while. Also, it's normally supplied as a 60% dispersion in mineral oil so you need to multiply the equivalence by 5/3 (apologies if you already knew this, just checking!)

I'd try a new pot of NaH and see if it helps.

Thanks a lot for your answer! When I say bis I mean bis(diethoxyphosphinyl)stilbene. I actually bought a brand new NaH so I am really out of ideas, why so much benzoin stays unreacted (calculations should be right). I perform everything under argon. I have done multiple experiments even with different equivalents of NaH, but it doesn't make much difference (yield range +- 5%) 

[edlovat]

Diethylchlorophosphate is fairly reactive, you can not use a milder base like diisopropylethylamine? Maby a catalyst like DMAP?

I also tried using pyridin, silver(I) oxide and LiHMDS as bases. Preparation with pyridin was the only one that afforded at least some usable conversion (43% it was if I remember it right). Thanks for your idea I will see if we have it in lab and might try it.
I am just wondering if I am not doing any huge mistake beacuse it is starting to be pretty frustrating 

[wildfyr]

I am just wondering if I am not doing any huge mistake beacuse it is starting to be pretty frustrating 

Welcome to organic chemistry! In all seriousness, water is by far the most likely culprit with an NaH reaction if you don''t feel confident with you dry technique. Make sure everything is bone dry: benzoin, diethyl chlorophosphate, and especially THF (sieves!). Clarkstill's comment about NaH purity is also very critical.

[edlovat]

Welcome to organic chemistry! In all seriousness, water is by far the most likely culprit with an NaH reaction if you don''t feel confident with you dry technique. Make sure everything is bone dry: benzoin, diethyl chlorophosphate, and especially THF (sieves!). Clarkstill's comment about NaH purity is also very critical.

I knew it's not going to be easy, but I am trying hard and giving the lab all my free time. I believe I am doing everything to make sure no water gets into the reaction. THF on sieves, I flame dry all my glassware... well thanks everyone for ideas!!

[rolnor]

I have seen people flame-drying Hamilton-syringes to the point the glass becomes deformed and they start leaking. If you use 10% excess reagent I do not think water is the big problem. Maby you could try the reaction without base? Then you probably need to heat.