Chemical Forums
Chemistry Forums for Students => Organic Chemistry Forum => Organic Chemistry Forum for Graduate Students and Professionals => Topic started by: Babcock_Hall on May 11, 2023, 09:59:09 PM
-
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?
-
Sulfamoyl is very different, not analogous to phenyl. The base seems to work so problem is somewhere else I think.
-
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.
-
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.
-
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.
-
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.
-
Great! We do miss things like this, now you have a method, lets not be to hard on ourselves.