I’ve been thinking a lot about cathinone recently. While methcathinone and mephedrone along with a million analogues have been abused to hell and back, cathinone itself is mostly restricted to the actual khat plant and apparently some party pills used in Israel back in the day. Reports on the effects are sparse, but probably it is similar to amphetamine but with about a third of the potency. This sounds like an interesting chemical to me, but most importantly, I want to know how quickly and under what conditions it decays to Cathine as it is said to do. For this reason, I’ve been brainstorming a synthesis. I wanted to run it by you guys before I tried it, to see if you can spot any obvious errors and maybe either warn me or soothe me about a particular step (bubbling ammonia through the reaction mixture). This is just a rough outline, I’ll do all the math before I actually mix anything of course.
Firstly I need to make propiophenone. The typical way involves propionyl chloride which is restricted, and making propionyl chlroide requires some heavy duty stuff like thionyl chloride or phosphorous trichloride which I don’t have. I did find a route using phosphorous and bromine to form phosphorous tribromide in situ and make propionyl bromide, but phosphorous is also difficult to get without scraping a million matchbooks. So, another route is needed.
I found a paper from 1963 called Decarboxylation Studies II. Preparation of Alkyl Phenyl Ketones by Charles Granito and Harry P Schultz which claims to produce propiophenone with 72 percent yield via dry distilling iron benzoate and iron propionate. Chemplayer tried something similar, but they used the calcium salts which probably contributed to the rather poor yields, as the calcium salts seem to require higher temperature. The authors of the paper formed the iron salts in situ, but this generates hydrogen and in combination with the flames probably needed to get this hot in an amateur setting this seems like a bad idea. Therefore, it seems wise to produce the iron salts first, then mix them and do the reaction. Here is my plan:
1 – Obtain propionic acid and benzoic acid. Both are regular old food additives so it shouldn’t be hard. Both can be had on various online stores, though the propionic acid is kind of expensive so I may prepare it from calcium propionate.
2 – React the benzoic acid with ferric chloride in water (can be purchased for etching circuit boards) this should make ferric benzoate and hydrochloric acid, the first of which is insoluble in water. Vacuum filter to get the relevant iron salts and wash with water to remove excess HCL.
3 – Do the same with the propionic acid, the iron salt of which I believe is also insoluble in water though this is less clear.
4 – Put the iron salts in an empty paint tin, 4 parts ferric benzoate to 1 part ferric propionate. I think the temperatures required and the iron oxide left behind might destroy glassware, so I think it is best to do it in a set-up similar to the way Benzene is made from sodium benzoate by NileRed in that one video. Paper says distillation occurred at 280-200 c which seems achievable with a camp stove.
5 –Distill over crude propiophenone. Then follow the work-up procedure in the paper I referenced: dilute with ether (I will probably use toulene), then wash with sodium carbonate solution in a sep funnel, evap off the solvent, dry (I plan to use magnesium sulfate) then distill (I plan to do this under vacuum from my aspirator pump) to separate from any lower-boiling diakyl ketones.
If this doesn’t work, I plan to do all of the tests that Chemplayer does in his video to confirm the presence of propiophenone. If its there but impure, I will maybe try to fractionally distill it. If not, I’ll probably have to fiddle with the tin-can reaction, but it may be bust.
From there, I just need to brominate the ketone and then react with ammonia to produce cathinone. However, I hate bromine, so I have an idea on how to form this in situ. I have heard conflicting things as to whether water harms this reaction, as Chemplayer says it does but others have performed it with HBr and 35% H2O2 which obviously both contains water and forms a good deal of water in situ. I assume Chemplayer is wrong here and water is fine. The somewhat scarce but OTC water sterilizer 1,3-Dibromo-5,5-dimethylhydantoin can therefore maybe be used here.
6 – Put propiophenone in a mixture of water and enough acetic acid to make it to go into solution. I’m not sure exactly sure how much this will be, but I plan to try and keep the acid to a minimum.
7 – Slowly add a tiny bit of 1,3-Dibromo-5,5-dimethylhydantoin and wait. This should react with the water and produce bromine, and thus hypobromous acid in situ. To deal with any nasty bromine fumes, I plan to suspend a glass funnel upside down a few inches above the neck of the flask with a clamp. Using a PET plastic tube, I will attach the stem of the funnel to my aspirator pump. This way, when vapors rise, they are are captured by the vacuum and scrubbed into the water reservoir by the action of the aspirator pump. Later, once the reaction is done, I can neutralize the water in the aspirator pump reservoir with sodium hydroxide and dump it down the drain without worrying too much about the environmental consequences. I plan to slowly add the pool chemical, wait for the evolution of a bromine-red color, then wait for its disappearance and then add a tiny bit more. Alternatively I suppose I could dissolve it in water and drip it in. I will add an amount of the dibromo pool chemical that can brominate all of the propiophenone, then add a little more, then wait for a few hours to make sure it has released all the bromine that it is going to. For now I plan to bubble some air through the solution to make sure no volatile bromine is dissolved in the mixture. If there is any, there could be a reaction of ammonia and bromine vapors in the next step that could form hydrogen bromide and nitrogen which would definitely be a bad idea.
8 – Once the bromination is done, I should be left with a solution of Dimethyhydantoin in acetic acid and water plus my product, alpha-bromopropiophenone. To convert it to methcathinone, I would add methylamine, but it is my understanding that to convert it to cathinone, I ought to add ammonia. To do this, I will just bubble ammonia gas through the solution by boiling an ammonium hydroxide solution in a separate flask to generate the ammonia, then affixing a stopper leading to another PET hose and a glass pipette. I will submerge the tip of the pipette in the reaction mixture so the ammonia bubbles through it. Excess ammonia fumes will be sucked up by the upside-down funnel I placed above the flask in the last step. If I haven’t misunderstood anything, the ammonia will neutralize the hypobromous acid and the acetic acid to ammonium acetate and ammonium bromide (or bromate?). Both of these are very soluble in water, as is the dimethyhydantoin, and so do not fall out of the aqueous reaction mixture as the ammonia is bubbled in. The ammonia will also react with the alpha-bromopropiophenone to form cathinone. However, because the ratio of acetic acid to water in the flask is rapidly falling as the acetic acid is neutralized by the ammonia, the freebase cathinone, which was held in solution by the acetic acid but is not soluble in water, will cease to be dissolved and form a layer at the bottom of the flask. Maybe. I’m not entirely sure about this bit. The amount of acetic acid and water may need to be adjusted so that the intermediate doesn’t become insoluble before it can react with the ammonia. I plan to just keep bubbling ammonia until the ph is basic enough and every bit of the tear-gas like effects of the brominated intermediate are gone.
9 – Then, I plan to pour the whole thing in a sep funnel. If the cathinone freebase has formed a layer of its own, I can just collect it, wash it a bunch with water, dissolve in a minimal amount of toulene, acidify with Hcl and then evap to get the cathinone hydrochloride. If not, I guess I extract the whole reaction mixture a couple times with some amount of toluene, wash that with water, acidify with Hcl and evap to get the cathinone hydrochloride. The second option requires more toluene and more time.
So, how does this sound? I am somewhat worried about neutralizing the flask with ammonia gas, I am unsure exactly how bromine and its related acids in aqueous solutions will behave here. I could first nuetralize it will sodium hydroxide or something, but I think if I do that all the acetic acid is nuetralized too and the brominatedpropiophenone ceases to be soluble before reaction with ammonia. Or, possibly I could add aqueous ammonia instead of ammonia gas. This might work too, though if the cathinone doesn't precipitate out, then the amount of reaction mixture would be a lot more in volume and require more extractions.
Any ideas? Any suggestions? Thanks.
Firstly I need to make propiophenone. The typical way involves propionyl chloride which is restricted, and making propionyl chlroide requires some heavy duty stuff like thionyl chloride or phosphorous trichloride which I don’t have. I did find a route using phosphorous and bromine to form phosphorous tribromide in situ and make propionyl bromide, but phosphorous is also difficult to get without scraping a million matchbooks. So, another route is needed.
I found a paper from 1963 called Decarboxylation Studies II. Preparation of Alkyl Phenyl Ketones by Charles Granito and Harry P Schultz which claims to produce propiophenone with 72 percent yield via dry distilling iron benzoate and iron propionate. Chemplayer tried something similar, but they used the calcium salts which probably contributed to the rather poor yields, as the calcium salts seem to require higher temperature. The authors of the paper formed the iron salts in situ, but this generates hydrogen and in combination with the flames probably needed to get this hot in an amateur setting this seems like a bad idea. Therefore, it seems wise to produce the iron salts first, then mix them and do the reaction. Here is my plan:
1 – Obtain propionic acid and benzoic acid. Both are regular old food additives so it shouldn’t be hard. Both can be had on various online stores, though the propionic acid is kind of expensive so I may prepare it from calcium propionate.
2 – React the benzoic acid with ferric chloride in water (can be purchased for etching circuit boards) this should make ferric benzoate and hydrochloric acid, the first of which is insoluble in water. Vacuum filter to get the relevant iron salts and wash with water to remove excess HCL.
3 – Do the same with the propionic acid, the iron salt of which I believe is also insoluble in water though this is less clear.
4 – Put the iron salts in an empty paint tin, 4 parts ferric benzoate to 1 part ferric propionate. I think the temperatures required and the iron oxide left behind might destroy glassware, so I think it is best to do it in a set-up similar to the way Benzene is made from sodium benzoate by NileRed in that one video. Paper says distillation occurred at 280-200 c which seems achievable with a camp stove.
5 –Distill over crude propiophenone. Then follow the work-up procedure in the paper I referenced: dilute with ether (I will probably use toulene), then wash with sodium carbonate solution in a sep funnel, evap off the solvent, dry (I plan to use magnesium sulfate) then distill (I plan to do this under vacuum from my aspirator pump) to separate from any lower-boiling diakyl ketones.
If this doesn’t work, I plan to do all of the tests that Chemplayer does in his video to confirm the presence of propiophenone. If its there but impure, I will maybe try to fractionally distill it. If not, I’ll probably have to fiddle with the tin-can reaction, but it may be bust.
From there, I just need to brominate the ketone and then react with ammonia to produce cathinone. However, I hate bromine, so I have an idea on how to form this in situ. I have heard conflicting things as to whether water harms this reaction, as Chemplayer says it does but others have performed it with HBr and 35% H2O2 which obviously both contains water and forms a good deal of water in situ. I assume Chemplayer is wrong here and water is fine. The somewhat scarce but OTC water sterilizer 1,3-Dibromo-5,5-dimethylhydantoin can therefore maybe be used here.
6 – Put propiophenone in a mixture of water and enough acetic acid to make it to go into solution. I’m not sure exactly sure how much this will be, but I plan to try and keep the acid to a minimum.
7 – Slowly add a tiny bit of 1,3-Dibromo-5,5-dimethylhydantoin and wait. This should react with the water and produce bromine, and thus hypobromous acid in situ. To deal with any nasty bromine fumes, I plan to suspend a glass funnel upside down a few inches above the neck of the flask with a clamp. Using a PET plastic tube, I will attach the stem of the funnel to my aspirator pump. This way, when vapors rise, they are are captured by the vacuum and scrubbed into the water reservoir by the action of the aspirator pump. Later, once the reaction is done, I can neutralize the water in the aspirator pump reservoir with sodium hydroxide and dump it down the drain without worrying too much about the environmental consequences. I plan to slowly add the pool chemical, wait for the evolution of a bromine-red color, then wait for its disappearance and then add a tiny bit more. Alternatively I suppose I could dissolve it in water and drip it in. I will add an amount of the dibromo pool chemical that can brominate all of the propiophenone, then add a little more, then wait for a few hours to make sure it has released all the bromine that it is going to. For now I plan to bubble some air through the solution to make sure no volatile bromine is dissolved in the mixture. If there is any, there could be a reaction of ammonia and bromine vapors in the next step that could form hydrogen bromide and nitrogen which would definitely be a bad idea.
8 – Once the bromination is done, I should be left with a solution of Dimethyhydantoin in acetic acid and water plus my product, alpha-bromopropiophenone. To convert it to methcathinone, I would add methylamine, but it is my understanding that to convert it to cathinone, I ought to add ammonia. To do this, I will just bubble ammonia gas through the solution by boiling an ammonium hydroxide solution in a separate flask to generate the ammonia, then affixing a stopper leading to another PET hose and a glass pipette. I will submerge the tip of the pipette in the reaction mixture so the ammonia bubbles through it. Excess ammonia fumes will be sucked up by the upside-down funnel I placed above the flask in the last step. If I haven’t misunderstood anything, the ammonia will neutralize the hypobromous acid and the acetic acid to ammonium acetate and ammonium bromide (or bromate?). Both of these are very soluble in water, as is the dimethyhydantoin, and so do not fall out of the aqueous reaction mixture as the ammonia is bubbled in. The ammonia will also react with the alpha-bromopropiophenone to form cathinone. However, because the ratio of acetic acid to water in the flask is rapidly falling as the acetic acid is neutralized by the ammonia, the freebase cathinone, which was held in solution by the acetic acid but is not soluble in water, will cease to be dissolved and form a layer at the bottom of the flask. Maybe. I’m not entirely sure about this bit. The amount of acetic acid and water may need to be adjusted so that the intermediate doesn’t become insoluble before it can react with the ammonia. I plan to just keep bubbling ammonia until the ph is basic enough and every bit of the tear-gas like effects of the brominated intermediate are gone.
9 – Then, I plan to pour the whole thing in a sep funnel. If the cathinone freebase has formed a layer of its own, I can just collect it, wash it a bunch with water, dissolve in a minimal amount of toulene, acidify with Hcl and then evap to get the cathinone hydrochloride. If not, I guess I extract the whole reaction mixture a couple times with some amount of toluene, wash that with water, acidify with Hcl and evap to get the cathinone hydrochloride. The second option requires more toluene and more time.
So, how does this sound? I am somewhat worried about neutralizing the flask with ammonia gas, I am unsure exactly how bromine and its related acids in aqueous solutions will behave here. I could first nuetralize it will sodium hydroxide or something, but I think if I do that all the acetic acid is nuetralized too and the brominatedpropiophenone ceases to be soluble before reaction with ammonia. Or, possibly I could add aqueous ammonia instead of ammonia gas. This might work too, though if the cathinone doesn't precipitate out, then the amount of reaction mixture would be a lot more in volume and require more extractions.
Any ideas? Any suggestions? Thanks.
