It’s one of those day… (a tosylation story)

EDIT (01-05-2013): It was a -Cl. The CNMR clearly showed 10 Dppm for the CH2 group for the starting material and the final purified product. Now it’s not reacting with the NHMe2… but this is another story… Thanks to all for joining the puzzle.

If chemistry is just like cooking (cit), doing a tosylation is like preparing a salad. Not very complicated and probably I did more than 300 in my life. But today was one of those day, and even a trivial reaction can be transformed in pure hell.

Let’s start with the beginning. I simply wanted to do this reaction, and as I told you before it’s pretty straightforward, so I didn’t check literature. I just dissolved everything in DCM, add 1.2eq of TEA and stir overnight.


The next day I did a TCL. One main spot that I purified by column chromatography:
Left: pyrene starting material. Center: crude. Right: purified product. Hex/EtOAc 1:2

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Then I dried it and went for the NMR. Here the funny part starts. I cannot see the tosyl group, not at all. So I run an NMR of the Pyrene starting material as well….
They are almost overlapping. Red trace: starting material. Blue trace: purified product. Integration on both 9 for the aromatics and 2 for the CH2 group. 0.05ppm difference in the CH2 group and In one you can clearly see the OH in the other one just water. (in CDCl3)


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Weird, let’s check the mass then… DART-MS. For both the main peak is 215, that fits with the dehydrated carbocation..
(Bottom: starting material, Top: purified product)

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Ok, maybe the DART is too aggressive, let’s check with the UPLC-MS. Here the things are getting even more weird. The two samples (starting material and product) have the same retention time…. (and naturally the same 215 mass peak)
(Bottom: starting material, Top: purified product)

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At this point I did another TCL from the sample run on the UPLC. (Left: pyrene starting material. Center: mixed starting material + product. Right: purified product). Hex/EtOAc 1:2

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Then the GC-MS, weird retention time (either the machine is not working properly or it doesn’t fly so well). Still peak at 215 and one weird at 280.

After a long brainstorming with a colleague (Massimo saw so many weird reaction in his life that he was my man for this TLC) we decided for the less weird hypothesis. “Probably” I’ve got the R-Cl instead of R-OTs. Then in the UPLC (water, ACN, FA) it get back to the alcohol, while on the TLC (org solvent) remain -Cl (cit: Treatment of Alcohols with Tosyl Chloride Does Not always Lead to the Formation of Tosylates).

So I react a little bit of the solid with dimethylamine for 2 hours…. nothing… same spot…

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Well, any idea? (I have to record a CNMR the day after tomorrow)


    • Vit

      I thought about it, but in the mass I should have seen a clear peak of the alcohol (or at least something). Other things I wonder about and then discarder were the tosyl-CH3 below the CH2, polymerization and/or the Friedel–Crafts.

  1. Brandon Findlay

    I’d guess Massimo is right, with a caveat. Acid catalyzes formation of a carbocation, which moves around the aromatic rings. This pops off the Cl via formation of a terminal alkene, which is then hydrated back to the SM.

    Try stirring in acidic water for an hour or so, then repeat the TLC (extr. into EtOAc if you need to).

    • Vit

      This seems to be the more reasonable idea. For this reason I put what I thought it was -Cl reacting with NHMe2 (that is the next step anyway). But they didn’t react. True this reaction is not catalyzed. Good point of trying to stirr it with acid water, I will give a try

  2. Santi

    Things to try:
    – reaction with NaI in acetone (to make the iodide, if it’s the chloride)
    -Add TBAI to the reaction with the amine, to catalyze it
    -A reaction with silver nitrate
    -make a grignard. quench it with D2O and GCMS

    Definitively that’s a Ar-CH2-X, so no SN2-prima-like reaction.

    And do no forget, that’s the paper for Tosylations (at least usual ones…):George W. Kabalka,* Manju Varma, and Rajender S. Varma, J. Org. Chem. 1986,51, 2386-2388 (Thanks to Peter F., I must say)

    • Vit

      thanks Santi,
      I was going to add silver (but then I didn’t find it, we are going to change the gross system finally)
      I’ll add TBAI to the reaction with NHMe2 that is already going if in two days nothing happened (you know, tomorrow it’s the last queen’s day)
      No way I’m going to do a grignard for this :-)

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