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I am attempting to deprotonate the methyl group on 2-methylbenzo[d]thiazol-6-ol (hydroxyl group is protected with a silyl group) in order to attach a phosphate group in the form of diethyl chlorophosphate. I have tried n-BuLi, LDA, NaH in DMF and THF at -78, 0, and 25 degrees Celsius and at reflux but none of these trials has resulted in any reaction apart from NaH in DMF at reflux, which resulted in the silyl protecting group falling off and unconvincing NMR evidence of the phosphate attaching. I need to attach the phosphate to allow a Horner-Wadsworth-Emmons reaction in the next step. Are there any other options I can explore?

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    $\begingroup$ Have you tried running the deprotonation and quenching with D2O? Your problem maybe with the chlorophosphate electrophile rather than with the deprotonation conditions. $\endgroup$
    – Waylander
    Feb 28, 2023 at 6:56
  • $\begingroup$ It has been done with the parent substrate: pubs.acs.org/doi/abs/10.1021/ja00069a016 $\endgroup$
    – user55119
    Feb 28, 2023 at 13:47
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    $\begingroup$ Alternatively, you may consider an Arbuzov approach. Brominate (NBS) the methyl group and react the bromide with $\ce{(EtO)3P}$ as done here. It has all been done on the parent substrate. $\endgroup$
    – user55119
    Feb 28, 2023 at 14:12
  • $\begingroup$ BTW: Welcome to ChemSE! $\endgroup$
    – user55119
    Feb 28, 2023 at 15:41

1 Answer 1

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The deprotonation of 1a has been conducted with LDA/THF and subsequently converted to the phosphonate.[1] Alternatively, bromide 3a has been prepared[2] and converted[3] to phosphonate 2a via an Arbuzov reaction. It also appears that your desired compound 2b has been prepared by the Arbuzov route from 3b. [4]

  1. G. Cai, N. Bozhkova, J. Odingo, N. Berova, K. Nakanishi, J. Am. Chem. Soc., 1993, 115, 7192. (The preparation of compound 11 (2a here) in the Experimental Section of this paper omits the addition of $\ce{(EtO)2POCl}$ (?)).

  2. T. Kotani, et al., https://www.jstage.jst.go.jp/article/cpb1958/45/2/45_2_297/_article

  3. L. Jiang, et al., RSC Adv., 2016, 6, 17318.

  4. Higuchi, Makoto, et al., Chem. Absts. Link not available.

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