Scheme 1 The preparation of 4-MMC HCl from 2-bromo-4-methylpropiophenone
4-MMC HCl was synthesized in two stages (Scheme 1). The first α-bromination step involved reacting 4-methylpropiophenone with excess bromine (to form 2-bromo-4-methylpropiophenone) in the presence of glacial acetic acid at 25 °C for 1 hour. The reaction solution was poured into ice-cold water and the 2-bromo-4-methylpropiophenone was extracted with dichloromethane and concentrated under vacuum to form yellow, fluffy crystals.
The final methamination step involved combining equal molar NaOH and methylamine hydrochloride solutions. This solution was then added dropwise over 1 hour to a stirred solution of 2-bromo-4-methylpropiophenone in toluene, and the mixture was allowed to stir for 32 hours at 25 °C and poured into ice-cold water.
The toluene layer was separated and acidified with dilute HCl solution, then the acidic extracts were washed with toluene before evaporating the aqueous layer to dryness to afford the crude 4-MMC HCl product as mottled light brown/brown colored, flaky crystals. Finally, the fine, white powder was collected following recrystallisation from isopropanol
The final product 4-MMC HCl was analyzed by using various chromatographic, spectroscopic, mass spectrometry platforms and X-ray crystal structure analysis. These analyses are helpful to set up rapid qualitative analysis of 4-MMC HCl.
4-MMC HCl was synthesized in two stages (Scheme 1). The first α-bromination step involved reacting 4-methylpropiophenone with excess bromine (to form 2-bromo-4-methylpropiophenone) in the presence of glacial acetic acid at 25 °C for 1 hour. The reaction solution was poured into ice-cold water and the 2-bromo-4-methylpropiophenone was extracted with dichloromethane and concentrated under vacuum to form yellow, fluffy crystals.
The final methamination step involved combining equal molar NaOH and methylamine hydrochloride solutions. This solution was then added dropwise over 1 hour to a stirred solution of 2-bromo-4-methylpropiophenone in toluene, and the mixture was allowed to stir for 32 hours at 25 °C and poured into ice-cold water.
The toluene layer was separated and acidified with dilute HCl solution, then the acidic extracts were washed with toluene before evaporating the aqueous layer to dryness to afford the crude 4-MMC HCl product as mottled light brown/brown colored, flaky crystals. Finally, the fine, white powder was collected following recrystallisation from isopropanol
The final product 4-MMC HCl was analyzed by using various chromatographic, spectroscopic, mass spectrometry platforms and X-ray crystal structure analysis. These analyses are helpful to set up rapid qualitative analysis of 4-MMC HCl.
