4′-Methylpropiophenone bromination to 2-bromo-4'-methylpropiophenone. Large scale.

[G.Patton]

Hello, sorry for a late reply. Temperature have to be less than 65 *C. I fixed this mistake, I apologize.

 

[Zetetic]

Greetings, dear G. Patton! Please pay attention to my question in this thread. You, in my opinion, are one of the most attentive and prompt experts among all forum participants.
p. s. I ask other forum members not to take offense at my words ;-)

 

[Zetetic]

Hello dear! If I use propiophenone and not 4-methylpropiophenone, do I need to change anything in this method? I hope to get bc-1 this way. And in the next step, from bq-1, through the method with ethyl acetate, acetone and hydrochloric acid, obtain an ephedron salt. Am I on the right track?

 

[G.Patton]

You have to recount reagent amounts according molecular weight of propiophenone.
Moles, grams, litres and chemical calculations

 

[DavidNichols]

Reaction temperature of 65 °C is simply wrong, since 2-bromo-4'-methylpropiophenone forms of crystals and lock 4′-methylpropiophenone inside. 2b-4m melting temperature is about 77 °C and it is very far from HBr boiling point. Consequently, 75-85 °C is a sweet range for your reaction temperature that should complete your halogenation roughly in 2 hours. The questions to answer:

1. will position of a bromine be right or you end with iso-mephedrone after amination?
2. will fraction of stereoisomers will be still 50:50 in this method?

 

[w2x3f5]

at elevated temperatures, side reactions are more likely, it is much better to carry out bromination in a solvent.
The question also arises about the decomposition of hydrogen peroxide at elevated temperatures, it is better to choose a replacement for this oxidizing agent.
so bromination without solvent and below the halogen ketone crystallization temperature is a very bad idea, there are complaints on the forum about the supplier of dirty halogen ketone in which there is a large admixture of the original ketone.

 

[DavidNichols]

I agree with you on using solvent for more even halogen distribution. H2O2 decomposition is unlike happen unless you reflux it up to 120-130 °C. The main issue is you having all the condition for di- and tri-halogenation. Stereo parity is also questioned, but its a pure speculation.

 

[w2x3f5]

Let's start with the fact that hydrogen peroxide self-decomposes over time during storage, naturally, the higher the temperature, the faster the decomposition, as well as local overheating when adding peroxide, where the temperature is much higher than the temperature of the reaction mass itself. Do not trust me, you can attach an empty bag to a reflux condenser and see how much oxygen is released from the decomposition of peroxide.
All conditions for polyhalogenation creates an excess of acid and the need to use peroxide in excess. I gave up peroxide a long time ago, it is the worst oxidizing agent for this reaction.

 

[ADATA]

The 2B4M produced in this way has a lot of impurities. I'm not sure what it is, the follow doesn't work

 

[Lev]

Good afternoon, tell me if it is possible to replace 4-methyloprofenone with another reagent
2-(1-bromoethyl)-2-(4-methylphenyl)-1,3-dioxolan ?

 

[w2x3f5]

hydrolysis of dioxalane up to 2b4m and further amination
maybe can do first amination after do hydrolysis, its need check in small amount

 

[Lev]

Bromdioxolane 98%

 

[w2x3f5]

new replacement 2b4m, obtained by conducting a halogenation reaction in a solution of ethylene glycol, standard protecting group for ketone

 

[Throw-off]

I was sent 2-bromo-4-Methylpropiophenone instead of 4-Methylpropiophenone, would sodium hydroxide reflux eliminate the 2-bromo?

 

[w2x3f5]

you can immediately obtain the substance you need from alpha-bromo-4-methylpropiophenone, write the CAS number of the substance you received

 

[Throw-off]

Appreciate your rapid response, I've utilised your write up of Microwave irradiation hydrolysis of BMK to P2P in the past actually, love your work friend.

Cas I received was 1451-82-70, desired end molecule I want is dl-ephadrine.

 

[Throw-off]

Thanks for your help, that motivation got me over the edge to work it out.

 

[w2x3f5]

Did you specify the number correctly? I find only number 1451-82-7
The substances of the CAS 1451-82-7 2-Bromo-4'-methylpropiophenone, from it you will receive MMC, it is enough to conduct an ammination reaction. Ephedrine you will not receive from this.

 

[Throw-off]

Won't you receive it in a two step process?

2b4m -> ephadrone -> ephedrine

 

[w2x3f5]

You need an ordinary propiophenone and then brominate and get alpha-bromopropiophenone, or you use the finished alpha-brophyophenone immediately.
How do you want to remove 4-methyl from MMC, I don't understand)))