A homework question asks:

The following reaction was carried out using ethanol or water as solvents, but gave poor yields in both cases. Suggest why this might be the case and how these problems could be overcome.

Deprotection hydrogenolysis

I've gathered that this is the deprotection step of a dipeptide synthesis reaction (Phe-Ser). The palladium catalyst and hydrogen gas remove the Cbz group from the n-terminal and the benzyl ester from the c-terminal, with a carbamic acid intermediate that spontaneously decarboxylates to the product.

I don't really understand why ethanol or water would give poor yields as a solvent, since I've seen multiple references where they use exactly those as solvents for this reaction (or methanol, or THF). The only hint I could find was a suggestion that using acetic acid may be necessary when deprotecting a Cbz group from an amine, since protonating the nitrogen facilitates the reaction. A couple of references said that an aliphatic amine could poison the catalyst and require the addition of dilute acid to protonate the amine...I'm lost on why or how the poisoning occurs.

A nudge in the right direction would be greatly appreciated.

  • 2
    $\begingroup$ This is a vague question (not your fault obviously). A poor yield might mean that you recover starting material, or that you get a different main product which could be a result of the desired product not being stable (for example if it cyclises). The poor yield might be a result of poor solubility, of poisoning the catalyst as you mentioned or maybe the yield will be improved if you heat the reaction and/or do it under pressure. I guess the answer is something that was mentioned in lecture but in general when you do research you should not be trying to answer vague questions. $\endgroup$ – K_P Nov 9 '14 at 19:43

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