A Practical Method For Stabilizing Lithiated Halogenated Aromatic Compounds
An exothermic decomposition was observed during a metalation/acylation of 3,4-difluoroanisole (5), resulting in a significant thermal hazard. The lithiated anion 6 was found to decompose exothermically at temperatures above −47 °C showing an adiabatic temperature rise at a peak rate of 120 °C/min. A...
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Veröffentlicht in: | Organic process research & development 2008-11, Vol.12 (6), p.1293-1298 |
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Hauptverfasser: | , , , , , , , |
Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | An exothermic decomposition was observed during a metalation/acylation of 3,4-difluoroanisole (5), resulting in a significant thermal hazard. The lithiated anion 6 was found to decompose exothermically at temperatures above −47 °C showing an adiabatic temperature rise at a peak rate of 120 °C/min. A literature search revealed similar observations for metalation/acylation in analogous aromatic difluoro compounds. This sequence of reactions was evaluated thermochemically. Control experiments at −55 °C over 2 h indicated anion 6 was stable at temperatures below −55 °C under dilute reaction concentrations. This runaway hazard could be addressed using MgCl2 to stabilize the reactive species and thereby decrease its decomposition rate. Thermochemical experiments suggested MgCl2 forms a weak interaction with lithiated species 6, rather than via complete lithium−magnesium exchange. The process was successfully piloted on a multikilo scale by use of MgCl2 as an additive. |
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ISSN: | 1083-6160 1520-586X |
DOI: | 10.1021/op8001596 |