Methyl amine w/ a sulfonyl chloride

  • #1
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Main Question or Discussion Point

Does anyone have any secret tricks to get this rxn to go? Usually a secondary amine with a sulfonyl chloride gives the sulfonamide really easily, but I am now trying it w/ methyl amine, which is obviously primary, and it does not want to go at all. I tried dissolving the sulfonyl chloride in ethyl acetate and adding the amine which LC/MS said didn't work. I also tried dissolving the sulfonyl chloride in ethyl acetate, adding 15 eq. of methyl amine, and some DMAP, still without success according to LC/MS. Anyone have any bright ideas on how to get this one to go?
 

Answers and Replies

  • #2
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Science Advisor
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Maybe add a little base? That's really weird. That reaction should go like a shot. Are you using neat MeNH2 or the aqueous solution? What about heating it up for a while?
 
  • #3
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I am using methyl amine in THF 2.0 M solution. When I add the amine to the solution a white precipitate forms, but its not my product. It is some mystery compound w/ a mass I don't recognize in the LC/MS. Can that extra proton on the amine moiety fall off and react w/ something else in the reaction? The UV trace on the LC/MS didn't show a peak for my desired compound at all. Would heating still help it then? I wish I could be more descriptive w/ the material I am working with, but its confidential.
 
  • #4
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Heh, I understand the confidentiality thing. Is it a heterocycle by any chance?

I would start by trying to add 2 equiv of triethylamine. The solid might be methylamine-HCl, but you should get at least some of your desired produce.

Does the LCMS hit for MeNH2 reacting with 2 equivalents of sulfonyl chloride? If that is the case then try an inverse addition (add a solution of the sulfonyl chloride dropwise to the MeNH2 solution).

Any other reactive functionalities in the sulfonyl chloride part?

You might also just try a test reaction with MeNH2 and tosyl chloride just to make sure that it isn't a problem with your technique or something. There ought to be a procedure for that exact reaction out there somewhere.
 
Last edited:
  • #5
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Hmm for some reason I got the reaction to go using the hydrochloride salt of methyl amine w/ some DIEA. Thanks for the suggestions though.
 
  • #6
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Hey, whatever works!
 

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