Chemistry Forums for Students > Organic Chemistry Forum for Graduate Students and Professionals
S- vs. O-alkylation using sodium sulfinates
Babcock_Hall:
Increasing the temperature to about 107 °C did not bring about completion of the reaction with diethyl iodomethylphosphonate. I am thinking of picking up some diisopropyl bromomethylphosphonate, which is the exact compound used in the patent.
Babcock_Hall:
--- Quote from: rolnor on March 25, 2023, 06:30:54 AM ---Sorry I did not see the post with thiopyridine. You should be aware that pyridine can be oxidized to the N-oxide with some oxidizers. Thiophenolate is a good nucleophile so it should work fine if you want to go that way. But thiophenol stinks, you can use bleach to remove the smell.
--- End quote ---
We made the sulfonyl phosphonate starting with 2-thiopyridine twice, in a two-step synthesis. Both times we had to run a column after the oxidation, something that we do not have to do when we oxidized the corresponding S-methyl sulfide to its sulfone. We are not sure about the identities of the side-products yet, but we may know more next week.
I decided to buy diisopropyl bromomethylphosphonate, and when it comes in, I will try a small test reaction along the lines of the protocol in the patent before committing more expensive starting materials.
rolnor:
The bromo would be much less reactive then the iodo, but thiolates will probably displace bromo quick anyway.
Babcock_Hall:
In this case the nucleophile is a sodium alkylsulfinate, and there will be tetrabutylammonium iodide as the catalyst. No yield was given in this patent. "A mixture of diisopropyl (bromomethyl)phosphonate (0.5 g, 1.93 mmol), sodium cyclopropanesulfinate (0.37 g, 2.895 mmol) and TBAI (0.071 g, 0.19 mmol) in DMF (4 mL) was heated overnight in a IOO0C oil bath. The mixture was cooled to it and diluted with EtOAc and water. The layers were separated, and the organic layer was washed with saturated NaHC03, brine, dried (Na2S04) and filtered. The solvent was removed and the crude was purified by silica gel to obtain the title compound."
rolnor:
Yes, the sulfinate is much weaker nucleophile than sulfide so it could be useful with TBAI. Cesium iodide would be easier to remove after the reaction.
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