Chemistry Forums for Students > Organic Chemistry Forum for Graduate Students and Professionals
S- vs. O-alkylation using sodium sulfinates
Babcock_Hall:
"A Simple Synthesis of Sulfones" Biswas G and Mal D, J. Chem. Res. (S) 1988 308.
Regarding this paper (which I mentioned in a previous comment), the authors used a sulfinic acid and deprotonated with DBU in acetonitrile. Yields were good.
rolnor:
--- Quote from: Babcock_Hall on March 10, 2022, 12:37:37 PM ---In the 1968 JOC paper by Meek and Fowler, dimethyl sulfate gave 88% sulfinate ester (from O-alkylation) and 12% sulfone (from S-alkylation), methyl tosylate gave 77% sulfinate ester, and iodomethane gave 7% sulfinate ester. All three of these reactions were performed in DMF, but the paper gives data on other solvents.
--- End quote ---
A alkyl sulphate is a hard electrophile so it goes for O-alkylation. A alkyl iodide is softer and will give more S-alkylation I think. O is a harder nucleophile than S.
rolnor:
--- Quote from: Babcock_Hall on March 09, 2022, 10:27:10 AM ---I am rereading Nigel S. Simpkins' 1993 book Sulphones in Organic Synthesis. There are at least two sections that deal with sodium sulfinates as nucleophiles to make sulfones. One section (starting on p. 11) discusses the S vs. O alkylation issue (the other section is on p. 60). This section mentioned that replacing methanol with polyethylene glycol as the solvent was advantageous. It also indicated that the product of O-alkylation, a sulfinate ester, could sometimes rearrange to make the sulfone. Another work-around is to run the reaction under conditions where the sulfinate ester hydrolyzes back to starting material. Eventually the sulfone is produced. The use of an ion-exchange resin to make the counter-ion a quaternary ammonium salt is also discussed. This section also discussed ultrasound as a method to speed up the reaction. In addition to an alkyl halide and TolSO2Na, one paper used DBU and acetonitrile. I am not sure what the DBU is doing, but I will try to obtain this paper and see (possibly the authors started with a sulfinic acid, as opposed to a sodium salt).
"A Simple Synthesis of Sulfones" Biswas G and Mal D, J. Chem. Res. (S) 1988 308.
The discussion that I am having the most trouble understanding concerns hard vs. soft electrophiles. The reaction of TolSO2Na with dimethyl sulfate gave almost entirely the sulfinate ester, but the use of methyl iodide gave predominantly the sulfone. It is surprising to me that the leaving group makes such a big difference, but the authors of the 1968 paper invoke hard and soft acid-base theory to explain it. It makes me think that there may be a difference between ICH2P(O)(OEt)2 and the corresponding tosylate in the reaction I am planning.
Meek JS and Fowler JS, J. Org. Chem. 1968 33 3422. https://pubs.acs.org/doi/pdf/10.1021/jo01273a014
Kielbasinski R...Mikolajczyk M. Tetrahedron 1988 44 6687-6692.
--- End quote ---
You should know that ICH2P(O) etc. is a poor electrophile, much less reactive than ordinary alkyliodides.
rolnor:
--- Quote from: Babcock_Hall on March 01, 2022, 08:42:54 AM ---We have used the two step synthesis you suggested (alkylation, then oxidation of the sulfide with Oxone or mCPBA) before, and we are doing so again this week. Oxone is easy to handle, and the oxidation reaction can be followed by P-31 NMR, as well as using TLC. In one case the sulfide is prohibitively expensive. In another, the thiol might be a bit volatile. In a third instance, I would like to make HOCH2S(O)R. Rongalite, the starting sodium sulfinate can be protected as the TBDMS ether, although the synthesis looks a bit inelegant, for lack of a better word.
--- End quote ---
In the end you gain by using this strategy, you can make the thiol yourself if expensive and if volatile just use a tight cap on the reaction flask.
hollytara:
Take a look at this paper: they did a lot of variations.
DOI: 10.1021/bk-1995-0614.ch009
Navigation
[0] Message Index
[#] Next page
[*] Previous page
Go to full version