Org Prep Daily

November 7, 2006

Look, ma – no methyl !

Filed under: mechanisms, procedures — milkshake @ 2:04 pm

A solution of 2-trifluoromethyl-4,5-dichloronitrobenzene 5.096g (19.6mmol) in neat N,N,N’-trimethylethylenediamine 10mL (77 mmol) was heated to 60C for 3 hours. The resulting deep-red solidified mass was suspended in water 40mL and sonicated for 15 minutes (untill a free-floating slurry formed). The precipitated product was collected by filtration, compressed on the Buchner funnel, washed thoroughly with water and dried on highvac. Y=5.221g (96.5%) of a deep-red crystalline solid.

1H(CDCl3, 400MHz): 7.146(s, 1H), 6.661(s, 1H), 3.493(m, 2H), 3.380(m, 2H), 3.020(s, 3H), 2.964(s, 3H); 19F(CDCl3, 376.5MHz): -59.33(s, 3F)


  1. That’s curious. Why trimethylethylenediamine and where/how did the extra methyl go/get abstracted? Is TMEDA.HCl the other product?

    Comment by Uncle Al — November 7, 2006 @ 2:47 pm

  2. Regular monochloro substitution is what one gets with a diamine that cannot form the second ring, N-Me piperazine for example (you get a mix of monosubst regioisomers in about 95:5 ratio).
    As you can see, I wanted to make something else, the regular monosubstituted product and was puzzled by the product spectra (and the fact the compound was pretty water-insoluble even after acidification). LC/MS solved the mystery.
    Phenyltrimethylammonium is a decent methylating agent in basic media and here the benzene ring has two electron withdrawing substituents. My guess is that the Me group transferred onto the starting amine (4 equivs used in the preparation) but I don’t know that for sure.

    Comment by milkshake — November 7, 2006 @ 3:10 pm

  3. What is the purpose of sonication?

    Comment by RCFuson — November 7, 2006 @ 8:35 pm

  4. Would trimethylethylenediamine formamide play nice? That’s close to becoming the second methyl group. Quaternize, demethylate, play the other end’s reduction against the nitro group.

    Comment by Uncle Al — November 7, 2006 @ 10:44 pm

  5. Sonication is often used to breakup solid masses. One has to be careful though because sonication can be a rather “energetic” process, resulting in undesired chemical reactions.

    Comment by milo — November 7, 2006 @ 11:27 pm

  6. Milo is right, I just needed to break the dumplings. It was not the high-power sonication with a sono-probe, just a regular sonobath used for cleaning glassware.

    Regarding Uncle Al’s suggestion on how to make the desired product: The protection on the second amino should work but one would have to be careful in choosing a good protection group that would not participate; for example tertiary amides are quite nucleophilic on oxygen. Anyway, the sub-project for which this was done is long dead and gone – and that’s why I can post the procedure here. My colleagues have noticed this blog already so I would get myself into a serious explanation problem if I posted too much on our current work.

    Comment by milkshake — November 8, 2006 @ 11:45 am

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