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Sulfamidophosphonate synthesis via n-butyllithium: ratio of starting materials

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Babcock_Hall:
Late last week I reacted (CH3)2NSO2CH3 with n-BuLi and then diethyl chlorophosphate.  We will purify next week, but there seems to be a little starting material and a new, slower-moving product.  I am cautiously optimistic. 

What surprised me was that the protocol used 1 equivalent each of the sulfonamide and chlorophosphate, and 1.1 equivalents of n-butyllithium.  They reported a yield of about 85%.  I have looked at a number of protocols for similar reactions, some of which were to produce sulfonyl phosphonates, and frequently only a half-equivalent of diethyl chlorophosphate is used.  I don't have references handy, but I will add them into this thread later.  When I discussed this some time ago, it was pointed out to me that the desired products (sulfonylphosphonate or sulfamidophosphonate) each have a more acidic hydrogen than the corresponding starting material, a sulfone or sulfonamide.

rolnor:
Yes, the product can protonate the lithio-species half-way through the reaction. So you get low yield. 2eqv. N-Buli+2 eqv. Methylsulphone might fix this. Then you get the product in its de-protonated form. I think the de-protonated product is a poor nucleophile compared to the lithio-methyl sulphone. You could make a large excess of the lithio-methyl sulphone and ad the chlorophosphate to this. The slow-moving by-product is probably the double-phosphonated methyl sulphone. If you do this, use very short reaction time, the lithio-methyl sulphone can attack the phosphonate ester I imagine. The chloro phosphate is very reactive, one minute is enough I think.

Babcock_Hall:
I have done a preliminary examination of the NMR data from two of the pools that I collected.  Both appear to be the desired product, in that the ratio of integrals in H-1 NMR is consistent with monophosphorylation of the anion.  The combined yield is 30%.  I am in the process of reviewing the literature of similar reactions again because we may need to perform this general reaction again soon.

rolnor:
Can the slow-moving product be the hydrolyzed phosphonate, a mono-ester? Maybe you can check them again on TLC, can it be they are the same, but the slow-moming was in the salt-form? Anion? A little bit imaginative.

Babcock_Hall:
The H-1 NMR integrals are inconsistent with that hypothesis.  Based on the corresponding process for sulfones, I would predict that adding the diethyl phosphonate group would increase polarity.  What was initially surprising is that the Rf values in the fractions were different from the Rf values of the crude product.  My hypothesis is that the crude product may have been overloaded on the TLC plate, which caused the discrepancy.  With the benefit of hindsight, we might have been able to save some time with a different solvent system.

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