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. 2019 May 24;24(10):1996.
doi: 10.3390/molecules24101996.

Flow Hydrodediazoniation of Aromatic Heterocycles

Liesa Röder  1 , Alexander J Nicholls  2 , Ian R Baxendale  3
Affiliations

Flow Hydrodediazoniation of Aromatic Heterocycles

Liesa Röder et al. Molecules. .

Abstract

Continuous flow processing was applied for the rapid replacement of an aromatic amino group with a hydride. The approach was applied to a range of aromatic heterocycles, confirming the wide scope and substituent-tolerance of the processes. Flow equipment was utilized and the process optimised to overcome the problematically-unstable intermediates that have restricted yields in previous studies relying on batch procedures. Various common organic solvents were investigated as potential hydride sources. The approach has allowed key structures, such as amino-pyrazoles and aminopyridines, to be deaminated in good yield using a purely organic-soluble system.

Keywords: continuous processing; deamination; flow chemistry; heterocylic; hydrodediazoniation; isopentyl nitrite.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
(a) The Vapourtech EasyMedChem system used to perform the experiments. (b) A diagram to show the general procedure of heterocyclic amine hydrodediazoniation.
Scheme 1
Scheme 1
The results from experiments using deuterated solvents, to show that the new hydrogen always comes from the alkyl tetrahydrofuran (THF) hydrogens and not acidic protons from the solvent.
Figure 2
Figure 2
The postulated mechanism for the formation of the aryl radical and termination to the target hydrogenated product.
Figure 3
Figure 3
A potential explanation as to why some substrates react more effectively under the presented procedure than others.
See this image and copyright information in PMC

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