Jump to main content
Jump to site search

Issue 64, 2018, Issue in Progress
Previous Article Next Article

Computational investigation of the control of the thermodynamics and microkinetics of the reductive amination reaction by solvent coordination and a co-catalyst

Author affiliations

Abstract

Amines are among the most important and frequently used chemical compounds due to their biological activity and a wide range of applications in industry. Reductive amination reactions are an efficient and facile route to synthesize long chain amines from sustainable sources by using a different available aldehydes and ketones, and a large variety of amines including primary, secondary and tertiary forms. The pathway of the reaction process is critically dependent on reaction parameters such as the pH of the reaction medium, choice of solvent (explicitly coordinating solvent) and process conditions. These parameters are affecting the reaction performance and the selectivity but are still not fully rationalized. Here, we investigate the microkinetics and thermodynamics of the individual steps of the reductive amination reaction by exploring the systems' parameters. Explicit water coordination to the aldehyde leads to a stepwise rather than concerted nucleophilic addition with a lower activation barrier by 6–10 kcal mol−1. At low pH, the pathway is changed by a direct protonation of the amine substrate. This protonation does not strongly affect the kinetics of the reaction, but the thermodynamic equilibria. The presence of an acid as a co-catalyst leads to the formation of an iminium intermediate and this drives the reaction forward. Thus, the presence of an acid as a co-catalyst clearly renders this pathway the thermodynamically preferred one. Consequently, altering the reaction parameters does not only influence the reaction kinetics, but also the thermodynamic profile of the pathways in all cases. Further understanding of the reaction dynamics is essential to develop a microkinetic model of the reaction to then control and engineer the process in order to rationally design routes to tailor-made products.

Graphical abstract: Computational investigation of the control of the thermodynamics and microkinetics of the reductive amination reaction by solvent coordination and a co-catalyst

Back to tab navigation

Supplementary files

Article information


Submitted
30 Sep 2018
Accepted
23 Oct 2018
First published
30 Oct 2018

This article is Open Access

RSC Adv., 2018,8, 36662-36674
Article type
Paper

Computational investigation of the control of the thermodynamics and microkinetics of the reductive amination reaction by solvent coordination and a co-catalyst

E. Boz, N. Ş. Tüzün and M. Stein, RSC Adv., 2018, 8, 36662
DOI: 10.1039/C8RA08135B

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material.

Reproduced material should be attributed as follows:

  • For reproduction of material from NJC:
    [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
  • For reproduction of material from PCCP:
    [Original citation] - Published by the PCCP Owner Societies.
  • For reproduction of material from PPS:
    [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
  • For reproduction of material from all other RSC journals:
    [Original citation] - Published by The Royal Society of Chemistry.

Information about reproducing material from RSC articles with different licences is available on our Permission Requests page.


Social activity

Search articles by author

Spotlight

Advertisements