3
$\begingroup$

Firstly, note that this is not a duplicate of Acid in Imine Formation. Clayden, Warren, & Greeves (2012) states explicitly on p. 231 that imine formation requires acid catalysis, and that the reaction takes place optimally under slightly acidic conditions, close to neutrality. This makes sense as we need to form the $\ce {-OH2^+}$ allowing water to leave. However, if we look at this list of literature, we would observe that most of the imine formation reactions do not necessarily require acidic conditions and some even take place under solely basic conditions. How do we explain this?

Reference

Clayden, J., Greeves, N., & Warren, S. (2012). Organic Chemistry (2nd ed.). New York : Oxford University Press Inc.

|improve this question
$\endgroup$
  • $\begingroup$ Most of the imine formation reactions do not start from an aldehyde and an amine. Furthermore, I believe that ‘if we look at this list of literature’ almost immediately constitutes a too broad question because each case is slightly different but I’m willing to leave it open. $\endgroup$ – Jan Dec 6 '18 at 17:07
  • $\begingroup$ @Jan The point I am trying to make from the reference to the list of literature is that acid catalysis is not a necessary condition for the reaction. I do not wish to discuss each particular case of the reaction mentioned in the list. $\endgroup$ – Tan Yong Boon Dec 6 '18 at 17:09
  • 1
    $\begingroup$ But in most of those cases involving carbonyls and amines, I can boil it down to ‘X supplies the acidic proton’ or ‘harsh conditions cause higher proton mobility’. $\endgroup$ – Jan Dec 6 '18 at 17:10
1
$\begingroup$

Formation of imines is usually a nucleophilic subsitution of oxigen with nitrogen. For this to happen, the oxigen usually must be bound beforehand as carbon-oxigen bond is quite strong. The most straightforward way is to use acidic catalysis.

Most reactions that you referenced use acidic catalysis, though sometimes it isn't immediately apparent because they use solid catalyst such as molecular sieves a.k.a. H-form zeolites. A few use Lewis acids, such as $\ce{Ti(OEt)4}$. They still count as acids.

The cases when no acid is used are not pure nucleophilic substitution. The reference you provided features various oxidative and other catalytic reactions, proceeding through different mechanism, that do not need acid, and a few reactions where reagent itself bears acidic function, like tosyl isocyanate, that is a strong electrophile and can bind with oxygen on its own.

TL;DR: the cases when acid apparently isn't used usually include it in non-obvious way. Other cases proceed through wild varying different mechanisms, usually involving oxidation.

|improve this answer
$\endgroup$
  • $\begingroup$ Good observation regarding the use of solid catalysts. But clearly, there are some reactions that use only basic catalysis on the list. For example, the 1st (J.-M. Huang, J.-F. Zhang, Y. Dong, W. Gong, J. Org. Chem., 2011, 76, 3511-3514) and second (L. Paquin, J. Hamelin, F. Texier-Boullet, Synthesis, 2006, 1652-1656) ones. How do you explain that? $\endgroup$ – Tan Yong Boon Dec 9 '18 at 11:52
  • $\begingroup$ @TanYongBoon In this caset the reaction is performed in heterogeneous system (benzaldehyde has very low solutbility in water) and includes extraction with organic solvent. Unlike the authors, I would rationalize this as reaction proceeding in organic phase, where alkylammonium salt acts as a weak acid, while unsubstituted ammonia remains in water phase. This is in agreement with their finding that the yield of the reaction increases in the row Cl<Br<I; since solutbility of ammonium salts in organic solvents increases in the same row. $\endgroup$ – permeakra Dec 9 '18 at 15:34

Your Answer

By clicking “Post Your Answer”, you agree to our terms of service, privacy policy and cookie policy

Not the answer you're looking for? Browse other questions tagged or ask your own question.