Deprotection with water ? Really.

Occasionally,  I have reservations about posting some of the articles I present.  Sometimes,  they may not be too practical,  I don’t endorse it as an article that you should try to scale-up.  But I get excited about these findings and want to share, especially when there is a green, environmental angle.  I am trying to suggest some articles that are worth looking at.  Having written a bit of a disclaimer,  I thought this was a neat paper using water at elevated temperatures.  Although this was done on small scale, could it be used for industrial scale ?  I was thinking that using water at high temperature would have require enormous heating and cooling requirements. You would have to test the chemical stability of your substrate when using WET (water at elevated temperatures).   It, still, is an interesting read (at least to me).  What seems really neat is the ability to tune the deprotection with two different protecting groups.  The article I am talking about is “Water at elevated temperatures (WET): reactant, catalyst, and solvent in the selective hydrolysis of protecting groups”, Charles L. Liotta et al, Green Chemistry, 2014, 16, 2147.  I never thought of using water at elevated temperatures but there are reasons why you would.  The dielectric constant of water decreases from 78 to 20 and the inherent properties allow it to solubilize organic molecules more readily as well as enhancing acid-catalyzed and base-catalyzed reactions.   The author of this paper was using titanium for the closed vessel construction because 316 Stainless steel was found to catalyze unwanted side-reactions.

The cases that are talked about in this paper are protecting groups for amines, mainly N-Boc (t-butyl carbamates) and N-Ac (acetamide) and OAc or acetate protecting groups for alcohols.  The N-Boc are the most easily removed at 150 °C, the acetamides and the acetates could be removed at 275 and 250 °C.

 

Selective deprotection of acetate in the presence of acetamide.

Selective deprotection of acetate in the presence of acetamide.

 

The yields are quantitative in most cases.  What do you think ?  It would help if you might answer the quick poll following this post.  I always appreciate the feedback.  Thanks.

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Stay tuned.

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4 thoughts on “Deprotection with water ? Really.

  1. Afraid the link didn’t work for me, so I remain unsure how fast the WET reactons go ? If rapid, then might be natural to think of flow chemistry rather than conventional reactors. That would simplify provision of Ti reactors in place of SS. Also by use of counter-current heat-exchangers thermal efficiency could be improved. Remaining problem of non-batch chemistry is then the potentially poor solubility of substrates/products when not at “WET” reaction temperatures – could lead to blockages, or else need for high dilution working.
    Worth posting, you never know…….

    Like

    • Hi Nick,

      I was thinking the same thing. With the multiple postings in more than one group,
      it is possible that you didn’t see my suggestion that perhaps a continuous flow reactor
      with microwave technology might work. It is definitely not something that I would have
      any experience with. I will fix that link. Thanks.

      Like

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