I have a phosphonium based zwitterion which has a carboxylic acid and a sulfonate group. The sulfonate exists as potassium salt (or the molecule has potassium as a counter ion). I tried standard acylation conditions (DCM/ drops of DMF/ oxalyl chloride) at room temperature. Oxalyl chloride was in excess, though. It turned out that both carboxylic acid and sulfonic acid were converted into their respective acyl chlorides. If we use 1:1 ratio, it is possible to selectively convert the carboxylic acid group into the corresponding chloride while keeping sulfonic acid intact? Thanks.
Did you try simple peptide coupling reagents, for example, DCC/DMAP, PyBOP, HATU, 2/4-NBsOXY, etc., there are many more. If you use one equiv. of the coupling reagent as well as the amine, you may get selective carboxamide formation.
You should try excess of thionyl chloride in benzene with drops of DMF to obtain the сorresponding chloride
I think that thionyl chloride is far more reactive than oxalyl chloride. It will certainly convert both carboxyl and sulfonic acid into respective chlorides, just as oxalyl chloride is behaving in excess amounts.
Dear M Farooq, could you please provide more details about your molecule?
Are you trying to make a carboxylic ester? If so, it might be easier to go ahead and esterify both acid groups rather than distinguish between them. Then selectively hydrolyze the sulfonate, which should be significantly more reactive than the carboxylate. This would work best if you are making an unhindered ester, preferably methyl.
Thanks for the replies. I would like to couple this zwitterion to a secondary amine via amide bond (of carboxyl) and rather than via sulfonamide bond. When oxalyl chloride was in excess, both sulfonate and carboxyl groups were converted into respective acyl chloride. Ideally, only the conversion of carboxyl to acyl chloride is required.
The molecule has propyl sulfonate and propanoic acid on a phosphorous atom (which exists as phosphonium).
This situation remains me the molecule of saccharine :). I think, if the methylation will be possible, the methyl solfonate will hydrolize very rapidly, yet the carboxylate will be relatively stable. Try methylation with diazomethane.
Dr. Rossen, the ideal situation is about converting the carboxyl group into acyl chloride followed by coupling with an amine. If both carboxylic+sulfonic acid are converted into their respective chlorides, the resulting sulfonamide and amide bonds will be very stable.
Did you try simple peptide coupling reagents, for example, DCC/DMAP, PyBOP, HATU, 2/4-NBsOXY, etc., there are many more. If you use one equiv. of the coupling reagent as well as the amine, you may get selective carboxamide formation.
Have you tried simply dean-starking the 1:1 mix of acid and amine? Might be an easy and simple solution. If not, perhaps a more sophisticated coupling agent like HATU or PyBOP might be the answer. You might also try P3T, but this might be too reactive.
For the interested readers, if we use 1:1 ratio of oxalyl chloride with a zwitterion containing both sulfonic acid and carboxylic acid, it resulted in 70% carboxyl acid chloride. The 30% was sulfonyl chloride. This is good enough for my purposes.
Convert the carboxyl group into methyl esters under neutral conditions using DMF acetals or ortho esters like trimethyl orthoformate. Then go for aminolysis of methyl esters.
I would go for some kind of protection for the sulfonate.....following this reference:http://pubs.acs.org/doi/pdf/10.1021/jo900122c, you can keep your sulfure acylated and back turn it into sulfonate post synthesis by mean of NCS....or in casa your sulfunate doesnt decompose, youi can protect it as TCE (trichloroethyl) derivative, afterword deprotected under basic conditions.
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