反应详情

A mixture of 4'-methyl-2'-chloroacetophenone and 4'-chloro-2'-methylacetophenone (98 g), [obtained by reaction of 3-chlorotoluene with acetyl chloride using the conditions of C R Noller and R Adams, J.Amer.Chem.Soc., 46, 1892 (1924)], methylamine (33% w/w solution in industrial methylated spirit, 130 ml), copper powder (3 g) and industrial methylated spirit (150 ml) was stirred in a sealed pressure vessel at 100° overnight. After cooling, further methylamine solution (130 ml) was added, the pressure vessel resealed and the mixture stirred at 100° overnight. The cooled mixture was washed out of the pressure vessel with industrial methylated spirit (2×200 ml) and then heated to 60°. Aqueous sodium sulphide nonahydrate (6.1 g in 60 ml water was added, the mixture stirred at 60° for 15 minutes and filtered through diatomaceous earth (sold under the trade name CELITE). The filter bed was washed with industrial methylated spirit (2×100 ml) and the combined filtrate and washings were evaporated to dryness under reduced pressure. The residue was stirred with hydrochloric acid (5M, 400 ml) for 2.75 hours and the resultant aqueous solution basified to pH 8 to 9 with aqueous sodium hydroxide (specific gravity 1.5). The mixture was extracted with dichloromethane (600 ml, then 2×400 ml), the combined extracts were dried over magnesium sulphate and the solvent was removed by distillation. The residue was dissolved in diethyl ether (500 ml) and the solution extracted with hydrochloric acid (5M, 3×150 ml). The diethyl ether solution was discarded. The aqueous extracts were basified to pH 8 with aqueous sodium hydroxide (specific gravity 1.5) and then extracted with diethyl ether (2×250 ml). The combined diethyl ether extracts were dried over magnesium sulphate and the solvent was removed by distillation. The residue was distilled under reduced pressure to give the novel compound 4'-methyl-2'-(methylamino)acetophenone, m.p. 47°.