title: Generation and Trapping of Ketenes in Flow.
abstract: Ketenes were generated by the thermolysis of alkoxyalkynes under flow conditions, and then trapped with amines and alcohols to cleanly give amides and esters. For a 10 min reaction time, temperatures of 180, 160, and 140 °C were required for >95 % conversion of EtO,iPrO, andtBuO alkoxyalkynes, respectively. Variation of the temperature and flow rate with inline monitoring of the output by IR spectroscopy allowed the kinetic parameters for the conversion of 1-ethoxy-1-octyne to be easily estimated (Ea= 105.4 kJ/mol). Trapping of the in-situ-generated ketenes by alcohols to give esters required the addition of a tertiary amine catalyst to prevent competitive [2+2] addition of the ketene to the alkoxyalkyne precursor.
authors.affiliation: Chemistry, University of Southampton Southampton, HANTS, SO17 1BJ, UK.
authors.forename: Cyril
authors.initials: C
authors.lastname: Henry
authors.affiliation: Chemistry, University of Southampton Southampton, HANTS, SO17 1BJ, UK.
authors.forename: David
authors.initials: D
authors.lastname: Bolien
authors.affiliation: Chemistry, University of Southampton Southampton, HANTS, SO17 1BJ, UK.
authors.forename: Bogdan
authors.initials: B
authors.lastname: Ibanescu
authors.affiliation: Chemistry, University of Southampton Southampton, HANTS, SO17 1BJ, UK.
authors.forename: Sally
authors.initials: S
authors.lastname: Bloodworth
authors.affiliation: Chemistry, University of Southampton Southampton, HANTS, SO17 1BJ, UK.
authors.forename: David C
authors.initials: DC
authors.lastname: Harrowven
authors.affiliation: Bioengineering Group, Faculty of Engineering and the Environment, University of Southampton Southampton, HANTS, SO17 1BJ, UK.
authors.forename: Xunli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: GlaxoSmithKline R&D Ltd., Medicines Research Centre Gunnels Wood Road, Stevenage, HERTS, SG1 2NY, UK.
authors.forename: Andy
authors.initials: A
authors.lastname: Craven
authors.affiliation: GlaxoSmithKline R&D Ltd., Medicines Research Centre Gunnels Wood Road, Stevenage, HERTS, SG1 2NY, UK.
authors.forename: Helen F
authors.initials: HF
authors.lastname: Sneddon
authors.affiliation: Chemistry, University of Southampton Southampton, HANTS, SO17 1BJ, UK.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Whitby
keywords: Acylation; Amides; Esters; Flow chemistry; Ketenes; Kinetics