Interesting writeup for 4-MMC HCL from 2-bromo-4-methylpropiophenone

[rampage]

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.

 

[rampage]

my queries are:
starting with 2-bromo-4-methylpropiophenone skips step 1. so only needs methamination? is this correct?
combing equal molar naoh and methylamine hydrochloride solutions, so methylamine hydrochloride solution is used instead of aqueous methylamine 40%? is this correct?
toluene is used, could a different solvent be used?

how do i work out how much 2-bromo-4-methylpropiophenone to start with?
then from that starting weight how much naoh solution? and %? and how much methylamine hcl solution? and what would the weight of methylamine hcl to water be?
how much solvent needed in reaction mixture?
how much ice cold water?
% of dilute hcl solution?

hopefully this inspires some interest and replies

also can the final product 4-methylmethcathinone hcl be used as the starting material to produce ephedrine?

 

[HectorFromTroy]

my queries are:
starting with 2-bromo-4-methylpropiophenone skips step 1. so only needs methamination? is this correct?
combing equal molar naoh and methylamine hydrochloride solutions, so methylamine hydrochloride solution is used instead of aqueous methylamine 40%? is this correct?
toluene is used, could a different solvent be used?

how do i work out how much 2-bromo-4-methylpropiophenone to start with?
then from that starting weight how much naoh solution? and %? and how much methylamine hcl solution? and what would the weight of methylamine hcl to water be?
how much solvent needed in reaction mixture?
how much ice cold water?
% of dilute hcl solution?

hopefully this inspires some interest and replies

also can the final product 4-methylmethcathinone hcl be used as the starting material to produce ephedrine?

rampage1.Yes starting with 2-bromo-4-methylpropriophenone only leaves you with the methylamination step.
2.yes
3.DCM can be used
4.I dissolve the 2-Bromo-4-Methylpropiophenone in minimum ammount of DCM then add twice the mass of the Bromoketone in methylamine 40%aq
5. You shouldn't need to use an ice bath
6.Procentage of acid shouldn't be that important you just have to make sure you don't over acidify or under acidify

 

[rampage]

1.Yes starting with 2-bromo-4-methylpropriophenone only leaves you with the methylamination step.
2.yes
3.DCM can be used
4.I dissolve the 2-Bromo-4-Methylpropiophenone in minimum ammount of DCM then add twice the mass of the Bromoketone in methylamine 40%aq
5. You shouldn't need to use an ice bath
6.Procentage of acid shouldn't be that important you just have to make sure you don't over acidify or under acidify

HectorFromTroythankyou for your input,
so ratio of bromoketone to methylamine 40% aq 1:2
and acidify to a ph of =?

 

[HectorFromTroy]

thankyou for your input,
so ratio of bromoketone to methylamine 40% aq 1:2
and acidify to a ph of =?

rampageyes I accidify until a 5-6 but be careful not to go lower then this, as for the Bromoketone to methylamine ratio it is what i found works best and balances good yields and relatively fast reaction times.