Question

40) .................is used as solvent for
preparation of Grignard reagent from
vinyl and aryl halides at higher
temperature.
​

Answer 1

Neal G. Anderson, in Practical Process Research and Development (Second Edition), 2012

III.D Entry of Water From Process Streams

Grignard reactions are notoriously sensitive to water, and two approaches to controlling H2O are shown in Figure 6.5. For homologation of the aryl Grignard with formaldehyde, Delrin® acetal was employed as shavings [40]; this homopolymer is effectively anhydrous, in contrast to sensitive to water, and two approaches to controlling H2O are shown in Figure 6.5. For homologation of the aryl Grignard with formaldehyde, Delrin® acetal was employed as shavings [40]; this homopolymer is effectively anhydrous, in contrast to formalin (∼50% H2O) or paraformaldehyde (5–9% H2O). (Some difficulties in cracking paraformaldehyde to produce gaseous HCHO have been described [41].) Lilly researchers conducted a detailed study on initiating the formation of a Grignard reagent and subsequent reaction with a morpholine amide [23] (as a substitute for a Weinreb amide). The free base from splitting the L-(−)-DTTA salt was extracted into toluene in the presence of THF, and the extract was dried by azeotropic distillation to 173 ppm H2O. Magnesium metal was activated with small amounts of both iodine and (iBu)2AlH at 60 °C, and formation of the Grignard reagent was initiated at 60 °C; at this temperature the reaction was found to tolerate greater amounts of H2O, up to 300 ppm. Then the extract of the free base was gradually added to the Grignard preparation. These conditions were robust enough to implement in the pilot plant.