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Acceleration of Anti‐Markovnikov Hydroamination in the Synthesis of an Active Pharmaceutical Ingredient
Author(s) -
Mitic Aleksandar,
Skovby Tommy,
DamJohansen Kim,
Gernaey Krist V.
Publication year - 2016
Publication title -
chemical engineering and technology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.403
H-Index - 81
eISSN - 1521-4125
pISSN - 0930-7516
DOI - 10.1002/ceat.201500673
Subject(s) - hydroamination , markovnikov's rule , chemistry , toluene , solvent , piperazine , organic chemistry , combinatorial chemistry , catalysis , regioselectivity
Slow chemical reactions are a big challenge in the modern pharmaceutical industry. Their accelerations together with the introduction of continuous manufacturing modes are major drivers for future development. One example reaction is hydroamination, a reaction between unsaturated hydrocarbons and amines. Such a reaction type is the main focus of this work. More precisely, the anti‐Markovnikov hydroamination reaction between cis/trans 9 H ‐thioxanthene‐2‐chloro‐9‐(2‐propenylidene)‐(9CI) and 1‐(2‐hydroxyethyl)piperazine (HEP) is investigated in detail. It has been traditionally performed in toluene with a huge excess of HEP and reaction times of up to 24 h. Acceleration of the reaction from 24 down to 4 h is achieved by switching from batch operation mode in toluene to either solvent‐free batch mode or microwave‐assisted hydroamination with tetrahydrofuran as a solvent.