Phenylacetone (P2P) synthesis from benzaldehyde with butanone

[Fenster]

Aldol Condensation.

The directions for this are in Organic Reactions



This write up seems to be more inline with what I am seeing. Has anyone actually tried to extract with solvent from the organic layer. Using chloroform won't work, as it's miscible with the organic layer. Unless I'm missing something the write up needs to be tested and modified.

Anyone tried this synth before.

 

[TheNut22]

OK. Just heat the benz-hyde and MEK with hydrochloric acid about 3-5 hours. Temp: 90-110 C.
Just thank me.

 

[Dj.Tizo]

Hi
Do I bubble hcl gas, or can I add to RM

 

[Sneaky.Base]

This method looks awesome, otc cheap chemicals.
Why expensive dcm while chloroform exists. If you want a long time coock you ll understand making chloroform is the job you have to do.
The write up method shared here is perfect, it shows it written by a professional . I ll wonder if there are any video a bout this method. Tnx for sharing this nice write up willi

 

[Mo0odi]

I support your words

 

[Dj.Tizo]

same here

 

[handle]

Great let's try this one.
Step 1, underway.
45g Benzaldehyde + 200ml M.E.K bubble the HCL gas from 25ml H2SO4 over 25ml Hydrochloric acid. Turned bright red in about 30mins, now stirring.

 

[handle]

Stage 1 completed.

 

[handle]

FAILED ATTEMPT, probably failed at stage 2! As I used 49% acetic acid and not glacial.

No precipitation.

 

[handle]

This is the only way a cowboy could test if he had made phenylacetone. No meth = not phenylacetone.

 

[OrgUnikum]

The product of the BV oxidation, the vinyl-acetate is miscible with Xylene, the P2P formed by hydrolysis is also miscible with Xylene, so anything what drops out is just crap. Filtration is a must if any of your intermediates or the final product in solvent is not clear but cloudy or turbid.

 

[TheNut22]

Thanks again. You have helped me alot with this whole synthesis, and the same time this has been a huge learning process.

 

[TheNut22]

No, the hydrolysis I made, I made it wayyyy more diluted KOH-solution.

 

[TheNut22]

Now I have perfecty clear yeallow P2P oily liquid.

 

[TheNut22]

I just tried to follow Uncle Festers provedure for cleaning my P2P, with 20% KOH many times and last time with dilured hydroc acid, but I've found out that it doesn't always go that path...

 

[OrgUnikum]

Uncle Fester is in prison now. Sadly not for all the crap he wrote in his books but for actually cooking and thats a shame.

Well Mr TheNut22, sorry to say, you followed UFs writings and got fucked. I mean it is not unknown that his writings are bullshit, well it is good stuff and bad stuff intimately interwoven in a way that it is all worthless as sorting this out is more work then just fiorgetting about it and going for better sources of information. Like the HIVE archives on EROWID. The wasps place. and more. No, not reddit, reddit is UF with a clowns-mask.

 

[TheNut22]

Yes, I think I've read almost the whole Rhodium about P2P and Leuckart. No, i don't read Reddit.
I was annoyed the Fester wrote hes books probably too wired from meth, and that's why they were quite difficult to read. But I give him the credit that when i read those, I was also interested to make my own amphetamines.

 

[TheNut22]

Thank you OrgUnikum, for making it clear to me that UF talks a lot of crap in its books, because I trusted them completely, especially when I was at the very beginning, and they were the only books I could find on the subject, before I found this good forum on this very same and many more related subjects.

One important thing that has puzzled me throughout this search for information is whether or not the ammonium formate will give the N-formyl derivative if I don't heat my formate with P2P enough to convert my "in-situ" ammonium formate to formamide? From what I've found on Wikipedia (I know...), but from many publications about Leuckart, e.g. from the Sceincemadness Wiki, I got the impression that if I don't heat the formate to make formamide "in-situ", I can make a primary amine directly with the Leuckart reaction, without the need for either acid or base hydrolysis. Is this true?

 

[OrgUnikum]

Ah the Leuckart is a riddle yes. What I can tell you is that ammonium formate is the reagent which reacts with the P2P, not formamide. Thats why the reaction with formamide alone does not work well but it does when formic acid is added. Comes out it is not the acid but the water in the acid (usually 15%) does the trick. This water hydrolyzes formamide to ammonium formate. When people use formamide alone they have for some reasons some water in the reaction - nobody here is working really anhydrous.
There is the so named "Ingersoll reagent" which is formate heated up to 170 °C and this is a mixturee of mostly formamide and a ammonium formate and this needs no formic acid or water added.
The low temperature Leuckart without the ester as intermediate, well I myself thought this sounds much more appealing. Does not work though. Not for what we are making. Why? I do not know, but it does not work.
What I know is: You need water (with formamide, not with Ingersoll, with formate you have to remove some water) - AND 160 °C and this is only possible with a VERY good condenser or a pressure vessel. You need to use a lot of formate/formamide. The hydrolysis of the ester is much faster with base then with acid and much lower concentration of base and lower temperatures are needed then commonly used.
The whole thing depends a lot on the quality of the reagents and I have no universal recipe, no golden bullet.

 

[TheNut22]

I noticed that when I first started making formamide in previous reactions, I did it exactly according to the "Inngersoll reagent", i.e. in temperatures of about 170 degrees C and then for 2 hours in temperatures of 150-160 degrees C and finally only in temperatures of 140 degrees C, and I thought I made pure formamide, but I usually left it at room temperature with the cap on the bottle to see if formate crystals still develop. Sometimes they came and sometimes they didn't. So, if I understood correctly, I made "Inngersoll reagent" at the time. Not pure formamide. And if that reagent wont work, no wonder I failed so many Leuckarts, with undistilled, but as pure as in the videos for making M-amph from P2P. Also right now my P2P looks just like in those videos. My steam distillation is now in halt, because my cheapest Vevor heating mantle broke. Cheapest, so now I will invest little bit more, so the stirrer don't break at the first week, jeesh!! Thank you very much for your answer!

 

[TheNut22]

First of all, now when I read third time your post, I got it. The "ingersoll reagent" works, but I always put formic acid in there, of course, because I had no clue about "Ingersoll-reagent". And my 85% formic is of course 15% water, so there it went wrong.

I have to ask you OrgUnikum: I have 10,58 g of P2P and 17,70 grams of ammonium formate in rbf.
I want to use catalyst when it's possible now, but my only catalyst now is properly made, and dried ZnCl2, wich according to 2 papers that I found about the catalysts in Leuckart, and Leuckart-like reactions, the ZnCl2 works as a catalyst. According to those findings they tell it's not the best nor the worst catalyst, but it still works and that's OK to me. Also, if I snap little piece of nickel plated metal (steel under the nickel plating, and no ZnCl2 in as a catalyst) in the reaction flask, will it help, or just mess up the whole thing? And last question: If I make Raney-Nickel, do I put it with the P2P and formamide/formate, or do I put it when I want to get rid of that N-formyl group (and I thought that is not an ester!)

What do you think?

 

[OrgUnikum]

Nickel catalyzed Leuckarts, I do not think it actually worked for anybody. Other catalysts the same. I don't know. As said, I do not have a golden bullet.

Raney Nickel + Ammonia in water + alcohol + hydrogen + 10 to 100 bar pressure and P2P of course. 80% to 95% yield. If you can melt Aluminium - go for it! Be aware that the addition of Nickel to molten Aluminium is very exothermic

 

[TheNut22]

I have to tell you OrgUnikum that of course I didn't think you had all the answers. But that's why it is good to read books, patents, publications from literature etc etc.. Just to you to say the Leuckart reaction doesn't work with lower temperatures, and I've read books, and books (Moore, Fester, Snow, "Dr Buzz"), and I have to just follow your instructions, when you have claimed so many, flase info, and this is JUST MY opinion. You don't know me. You don't know my age, and education.

I'm curious when you said: "Does not work though. Not for what we are making. Why? I do not know, but it does not work."

I don't understand this: What you meant by 160 C? Reaction temperature with formate? And if so, if it is like that, to make formamide "in-situ", that I can fully accept and relate. You also wrote something about to need a very good column when to be heating to 160 C, and some pressure. Why? What did you mean? I have 3 different ones and I use a straight column for dewatering and 100-120C for a few hours until I'm happy with reaction mixture, when P2P is fully mixed with melted formate or waterless formamide. You also claimed, the water is doing the trick when using formic acid with formamide. I don't know what is that claim, but I wouuld put just water without that "useless" formic acid in the reaction mixture. Formic acid can be used many hydrogenations. It is also quite common to use with nickel in reductions, and Leuckart, like we all should know, is reductive amination process. Formic acid as reducing agent and ammonia as an amine source, to make it simple but also right. In Leuckart is good to use formamide with just catalytic amount of ammonium formate as a catalyst (0.1-0.5 molar equvalent). This is common knowledge.

I'm really still a beginner, and learning every time especially from good conversations, books, etc. But I don't learn when you say like you just know, but cannot explain even to give a hint. That is something that I take as someone is just playing with me. Leuckart hates water. Catalysts are usable tools.

 

[OrgUnikum]

160 °C is the wanted temperature in the reaction. Water can come from adding water to anhydrous formamide, using a mixture of formamide and ammonium formate (Ingersoll reagent) or by adding 85% formic acid (contains 16 % by weight water).
At 160°C the reaction will expel more water then you want removed if you do not either use a powerful condenser (Intensiv condenser with cooling mantle and coil insides) running with very cold water or you run the reaction under some pressure what raises the boiling points and you keep the water in this way.

You do not have to follow my instructions as there are none regarding the Leuckart only suggestions and warning of things which are known not to work.

I would attach some articles I find interesting but one cannot attach .pdf files anymore what makes qualified conversations here neigh to impossible.

 

[TheNut22]

Yes, I have 85% formic acid, and from ammonium formate, there comes the water, wich have to be removed. The waters that come from the formic acid and ammonium formate must be removed. That's why I use hand-warm water for 2-3 hours in the condenser. When I notice that the melted formate and P2P and other reagents or catalysts are in molten harmony with each other, I replace the condenser with ice-cold water and raise the temperature little by little, and finally to about 155-160 C when using ammonium formate. With formamide, I raise the heat faster, but steadily, and to about 165-170 C. AlCl3 has been the most reliable catalyst, at least according to the literature, and I have often succeeded in making the product up to the n-formyl derivative. I believe that everything has gone wrong when I have not been able to gasify the product, but I have tried to make it either sulfate with H2SO4 + 95% ethanol, or with hydrochloric acid + acetone. Is gassing really that important? Thanks again for the practical answer OrgUnikum!

 

[OrgUnikum]

Nobody gasses Amphetamine. The HCl salt of it is virtually unusable as it is highly hygroscopic, sucking water from the air, creating a puddle and running off.

Whats important is filtration and washing plus (steam)distillation of the base. I posted the whole post-reaction procedure already twice here I think, might be well one of my first posts on the board.

The only drug I know which lends itself to gassing is d-Meth. Already racemic meth is not good for it as it forms ultrafine crystals then which are even with vacuum not to filter, you would need a filterpress or such. Big hassle. Better titrate and evap.

 

[TheNut22]

Can you tell me if the mixer piece was the wrong size, or why it bounced around when I tried to mix? I put a new stirrer piece in the new 500ml rbf. I was preparing diphenidine from deoxybenzoin and piperidine. I'll try again because it's a really simple synthesis. At least on paper..hehh. It was my first magnetic stirrer and I messed up the settings. Now it blew the fuse, so now it's in the trash. By the way, can you advise which solvent and catalyst should be used, or should actually be used in such a reaction? As I remember, I used alcl3, and I couldn't find the whole synthesis anywhere, but I followed some patents (different compounds made from deoxybenzoin and ...). The patent concerned different analogues of diphenidine (pyrrolidine etc.)

And, thank you for your advice to Leuckart reaction! I will try it when my new heating mantle in at my door.. hehh

 

[TheNut22]

OrgUnikum: I didn't get it now. Should I use very cold water, that I use, or should I put "not-so cold" water in the condenser?
And: Should I use: That condenser that have spiral in it, or fractional column (made so it haves some shards inside), or
straight and wider condenser, or do I use my fourth condenser where it's wide, narrow, wide, narrow? Sorry I don't have the proper names of those condensers on my desk at the moment. Like everybody will notice, I'm not very experienced cooker, but I know alot of theory, and I've made couple of successfull compounds. However, my methcatinone is my bravura'. Made it many years.

 

[Chemist Jun]

The goal of the condenser is to condense steam from the gaseous state to the liquid state. This is its mission
Very cold water improves the efficiency of the condenser
The screw condenser works well, has a longer space, and also features a screw choke

 

[TheNut22]

Wow, I didn't know that! Yes, that is the purpose on condensers. I was asking about those pressures with different condensers, because I haven't read anywhere about different pressures, but now I'm thinking yes, I think there is little bit more pressure at 160 C, with spiral condenser than of that straight, wide one.

 

[Chemist Jun]

don't know the truth behind that
But let me tell you that it is safe at low temperatures. They prefer it because of its low boiling point and it does not catch fire.
Perhaps chloroform is also close to it
The best is diethyl ether, but deal with it with expertise and avoid it because it causes ignition if its vapor comes into contact with an open flame.
There are safe alternatives to toluene, gasoline, hexane..

 

[Chemist Jun]

You are good at chemistry, don't let Dcm or chloroform get the better of you
Be strong and try with the solvents available in your country
Or multiply ethanol with sulfuric acid and make a wonderful solvent. If you bring these two reagents, sulfuric acid and ethanol, raise your flag now and make diethyl ether.