What is the optimum range of pH for the formation of Schiff Bases by the addition of hydroxylamine to an aldehyde or a ketone?

According to Peter Sykes' A Guidebook to Mechanisms in Organic Chemistry,

"The initial addition step or the dehydration step can be made rate limiting at will, depending on the pH of the solution. At neutral and alkaline pHs it is generally dehydration, that is the slow and rate limiting step while at acidic pHs it is the initial addition which is slow and rate limiting. This clearly has significance in preparatory terms, and formation of such derivatives of carbonyl compounds tends to exhibit pH optima."

My doubts are :

  1. How does the pH change the rate limiting step? That is, why is dehydration the rate limiting step at neutral and alkaline pHs and why is addition the rate limiting step at acidic pHs?

  2. What is the significance in preparative terms that Sykes is taking about?

  3. How will this significance determine the pH and what is that pH (or the range of pHs)?


1 Answer 1

  1. Dehydration requires protonation of the hydroxy intermediate, this clearly is slower at neutral or alkaline pH. Hydroxylamine is basic so at acidic pH it protonates making it non-nucleophilic hence lower pH slows the rate.

  2. Time taken for the reaction to go to completion. If the rate is slowed then other competing reactions (e.g. self-condensation) can and do reduce your yield.

  3. The pH will vary for each substrate and needs to be experimentally determined. This is where a literature search saves you a lot of grief.

  • $\begingroup$ Can you tell me how to find the relevant literature? I am new to this and can't seem to find any papers or any book on the web that carries the information I need. I specifically require the pH when the substrate is acetaldehyde. $\endgroup$ Nov 5, 2018 at 17:42
  • $\begingroup$ This depends on the resources available to you. Do you have access to online databases such as Scifinder or Reaxys? If not a Google search on "acetaldehyde oxime synthesis" turns up multiple references to papers, patents and procedures such as this prepchem.com/synthesis-of-acetaldoxime which looks perfectly viable and contains further references $\endgroup$
    – Waylander
    Nov 5, 2018 at 18:01
  • $\begingroup$ Thanks for the link. While it doesn't mention the pH, it does have further references. How do I access the referenced papers? I could not find the paper by searching its name on Google. $\endgroup$ Nov 5, 2018 at 18:30
  • $\begingroup$ You need some form of subscription through your college library/employer to access American Chemical Soc/Royal Society of Chemistry papers. $\endgroup$
    – Waylander
    Nov 5, 2018 at 18:48

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