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Topic: no reaction among diethyl methylphosphonate, LiHMDS, and a sulfamoyl fluoride  (Read 2529 times)

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Online Babcock_Hall

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In the literature from 1998 is a protocol for a reaction involving  diethyl methylphosphonate, 2.2 equivalents of LiHMDS, phenylsulfonylfluoride, to produce phenylsulfonylphosphonate within 90 minutes at room temperature (the authors do not discuss whether or not they took a time point in less than 90 minutes).  The reagents are added successively at -78 °C, and the reaction is then allowed to warm to room temperature.  I performed this reaction, and the crude product had the appropriate chemical shift of roughly 11 ppm (it was a test reaction, and I did not purify the product).  I tried the analogous reaction with dimethylsulfamoyl fluoride on a small scale.  After roughly 32 hours, I quenched an aliquot with HOAc, removed volatiles, and took a P-31 NMR.  I saw a single peak near 31 ppm, which is within a ppm of one published value for diethyl methylphosphonate and about 20 ppm away from a typical sulfonyl phosphonate.  I expected that the sulfamoyl fluoride would be slower, but I have little to judge on how much slower.  The LiHMDS was old but was unopened.

The majority of the test reaction is still unquenched and I could simply let it stir for a week (nothing is likely to happen IMO), or I could try to reflux.  The only other two things I can think of are to use a stronger base and to use the opposite synthetic disconnection.  Thoughts?

Offline rolnor

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Sulfamoyl is very different, not analogous to phenyl. The base seems to work so problem is somewhere else I think.

Online Babcock_Hall

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I tried heating (the oil bath was at 70 °C) for about seven hours and took another time point.  The S/N for the phosphorus spectrum was low.  Neither the P-31 spectrum nor the H-1 spectrum showed evidence of a substantial completion reaction, in a preliminary analysis of the data.  It is possible that a small amount of product was formed.  My tentative conclusion is that the sulfamoyl fluoride is quite a bit less reactive than a sulfonyl fluoride. I was expecting some decrease in reactivity, but not this much.  I have worked out a couple of other disconnections to the target molecule, but I will pursue some other chemistry first and come back to this part of the project later on.

Online Babcock_Hall

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Besides the reduced electronic reactivity of a sulfamoylfluoride versus a sulfonyl fluoride, it occurs to me that there might be a bit of steric occlusion from the two methyl groups on nitrogen.
« Last Edit: May 16, 2023, 02:56:22 PM by Babcock_Hall »

Offline rolnor

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Can you buy the chloride? The fluoride might be very unreactive, as you point out, the nitrogen donates electrons to the sulphonyl, very much so.

Online Babcock_Hall

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I did some additional searching using SciFinder, and the sulfamoyl chloride is commercially available..  Although I did not find as much as I was hoping on the conversion of the sulfamoyl chloride, I did find a protocol that used a different disconnection to the very compound that I wish to make.  This strategy uses n-BuLi to deprotonate the sulfonamide, which then attacks diethyl chlorophosphate.  I am not sure how I missed this reference previously.
« Last Edit: May 22, 2023, 11:12:26 AM by Babcock_Hall »

Offline rolnor

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Great! We do miss things like this, now you have a method, lets not be to hard on ourselves.

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