Hello everyone, in this thread I would like to discuss issues related to the synthesis of your favorite 4MMC. I propose to discuss here the well-known and experimental ways of obtaining 4MMC, to analyze how suitable the recipes that neural networks throw are suitable. But to start the topic, I would like to share my advice on the synthesis of 4-Methylpropiophenone. Specifically, I am interested in how difficult this process is. I am also interested in how strong the smell will be when using chemicals equipment. Those who have dealt with this, I want to hear your opinion. I say in advance: I am interested in the process of 4-Methylpropiophenone synthesis, and not in buying it, and I am not given other options.
Question All about 4mmc synthesis routes
- Thread starter The_Grand_Duel
- Start date
The process is about as difficult as making a "Just add egg" cake. 4-MMC from 2b4m is "just add methylamine". Obviously it gets much more difficult if you decide to synthesize your own 4-methypropiophenone and brominate it.
To minimize the smell you have to use methylamine hydrochloride (MMA.HCl) instead of methylamine 40 % (aq). Having tried both I can tell you the difference is massive and the method that adds NaOH solution into the reaction vessel, followed by adding MMA.HCl, gives away minimum smell, almost hardly any methylamine smell at all. MMA.HCl in its crystal form is odorless and once added into the RM you can seal the reactor and contain the smell which is a huge advantage for anyone who has to be concerned about the smell.
One thing that is criminally under-discussed is so called "acidification in aqueous environment". Instead of using acetone and worrying about the strength of HCl and losses through dilution of 4MMC.HCl in water, no acetone is used during acidification. Instead, HCl (aq) is added straight into the free base, depending on its strength some extra water might be needed, and 4MMC.HCl is allowed to dissolve in the added water (part extra, part contained in HCl) instead of forcing it to precipitate out of the solution. You separate the aqueous layer from the organic layer that contains remaining solvent used for the reaction, and proceed straight into crystallization. Wash the 1st generation crystal with freezer-cold acetone and recrystallize again. This process may take more time but you'll save significant amounts of acetone (which may be important to someone who wants to keep purchases to the minimum) and you'll prevent a sea of problems from possible aldol condensation and other reactions involving acetone that may occur during acidification.
To minimize the smell you have to use methylamine hydrochloride (MMA.HCl) instead of methylamine 40 % (aq). Having tried both I can tell you the difference is massive and the method that adds NaOH solution into the reaction vessel, followed by adding MMA.HCl, gives away minimum smell, almost hardly any methylamine smell at all. MMA.HCl in its crystal form is odorless and once added into the RM you can seal the reactor and contain the smell which is a huge advantage for anyone who has to be concerned about the smell.
One thing that is criminally under-discussed is so called "acidification in aqueous environment". Instead of using acetone and worrying about the strength of HCl and losses through dilution of 4MMC.HCl in water, no acetone is used during acidification. Instead, HCl (aq) is added straight into the free base, depending on its strength some extra water might be needed, and 4MMC.HCl is allowed to dissolve in the added water (part extra, part contained in HCl) instead of forcing it to precipitate out of the solution. You separate the aqueous layer from the organic layer that contains remaining solvent used for the reaction, and proceed straight into crystallization. Wash the 1st generation crystal with freezer-cold acetone and recrystallize again. This process may take more time but you'll save significant amounts of acetone (which may be important to someone who wants to keep purchases to the minimum) and you'll prevent a sea of problems from possible aldol condensation and other reactions involving acetone that may occur during acidification.
- By Ditonator229
That is, the aqueous solution of methylamine has the strongest smell of all reagents at this stage, but I also wonder how in the process of cooking 4mp (acylation of toluene by the Friedel-Crafts reaction) it is possible to avoid an obvious smell? I think propionyl chloride itself is a very good reagent, have you dealt with it?
Okay, thank you for the answers, but I am interested in what other Lewis acids can be used in addition to alcl3, I heard that zncl2 and fecl3 are also used, they are cheaper, they are easier to find, I understand that then the yield will decrease a little, but the main question is whether the reaction will take at the same temperature, how long will the reaction last? And also, if the toluene is removed from the solvent (that is, a little not clean), will it work??