Generation and Trapping of Ketenes in Flow

• Published in: European journal of organic chemistry Vol. 2015; no. 7; pp. 1491 - 1499
• Main Authors: Henry, Cyril, Bolien, David, Ibanescu, Bogdan, Bloodworth, Sally, Harrowven, David C., Zhang, Xunli, Craven, Andy, Sneddon, Helen F., Whitby, Richard J.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.03.2015; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Subjects: Acylation; Amides; Chemistry; Chemistry, Organic; Esters; Flow chemistry; Ketenes; Kinetics; Physical Sciences; Science & Technology; ACIDS; Flow chemistry; ACETYLENIC ETHERS; EFFICIENT SYNTHESIS; Amides; Esters; ALKYNYL ETHERS; Ketenes; DISCOVERY; AMINES; CHEMISTRY; Kinetics; BOND; Acylation
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201403603

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, and tBuO 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. Ketenes are generated under flow conditions by thermal sigmatropic rearrangement of alkoxyalkynes. Subsequent trapping with amines or alcohols gives amide or ester products, respectively. Inline monitoring by IR spectroscopy and offline analysis by 1H NMR spectroscopy allow the rapid study of kinetics and optimisation of the reaction.