Phenylacetone (P2P) synthesis from benzaldehyde with butanone

[MadHatter]

Why would you want to replace chloroform? It's easy to synthesize yourself with acetone and bleach. Check youtube.
But if you really need to for some reason, dichloromethane and chloroform are usually interchangeable.

 

[TheNut22]

I tried DCM for the first time, and it failed totally.
I extracted the product with ethyl acetate (more) and xylene (less)-mix.

 

[Cbison]

How do you get the MPB to solidify? In the freezer i see the crystals but outside the freezer it liquifies.

 

[MadHatter]

I guess what I'm really wondering about is the stochiometry of this reaction. In other write-ups of the bayer-williger I can't seem to find this enormous amounts of GAA. Can somebody help me with the rationale? I'm really close to trying this one out, but the amount of GAA is problematic.

 

[billythekid]

this amount of gaa is a lot and my best guess as to why is that preparing Peracetic acid in situ (during the reaction) and without a catalyst is inefficient so the chemist overcompensates to help with this, also GAA is used here as the solvent
by making the peracetic acid days before and testing the available oxygen content you are likely to get better results. This being said, I have seen professionals use this method and only get at best 35 to 65% of finished product. so an inexperienced chemist is likely to get even worse and a newbee is likely to fail or even worse hurt themselves. I recommend reading and studying and start small
make sure you thoroughly clean your finished reaction mix at the end of each step, Do not exceed -5c in the aldol condensation let mek/benzaldehyde stir overnight in the fridge after gassing.
do not exceed 60c in the Bayer villager. and research other oxidizers because I get better results with a different one.

 

[TheNut22]

I have 50 grams of methylphenylbutenone. Is 300 ml:s (exept from 500 ml:s of GAA) of GAA enought to make peracetic acid in situ with 65 g of 50% H2O2? Because if I put that 500 ml:s, I think that is too much, like many says.
So, is that 300 ml:s of GAA enough?

 

[TheNut22]

It seems like it dissolved all, so I think 300 ml:s of GAA is enough. Thoughts?

 

[TheNut22]

...Aaannd, I put 3 ml:s of ~75% sulfuric acid in there, and put the whole shebang together to my closet for at least 12 hours. Maybe around 24 hours, and then start heating it for 6 hours at temperatures: 50 - 55 C. Is this correct?

 

[billythekid]

you dissolved the mpb in the acetic acid already? or did you make the Per acetic first?

 

[billythekid]

y i re read your response and it sounds good add the per acetic acid dropwise and dont let the reaction temperature goi above 55 c addition of the per acetic acid is going to be exothermic

 

[billythekid]

yes thats alot of glacial acetic acid there should also be acetone in there too but with the extra acetic you should be okay but dont expect a huge yeild reflux at 55 for 24 hours

 

[TheNut22]

I got ~ 7 grams of sweet smelling little bit yellow P2P from 35 grams of MPB. My peracetic oxid time was around 24 h.
Now I've done the Leuckart reaction, at 32 h time. I have my n-formyl --... now. I am proceeding hydration with base (KOH pellets with pure water, 5 hours reflux), with that kind of reaction some paper claimed as good as 95% yield!?
I don't know, but this time, the look (got purple solution, but it's OK) and smell is different from my many attempts to proceed the Leuckart reaction, but I think I didn't have P2P then, but now I certainly did! Yes! Just never give up!
Because this was my 22:nd attempt..

 

[lalalander]

Have you ever tried oxidizing MPB with oxone? In thevespiary it was written that by oxidizing with oxone, 85%> yield was obtained.

 

[billythekid]

can you provide the link please
i have used oxone and followed many procedures from that site and never did i see any that claimed such high yeilds

 

[TheNut22]

No I haven't tried that.

 

[OrgUnikum]

You are right. Without H2SO4 as catalyst you need mad amounts of GAA to get peracetic acid as acetic acid is simply not strong enough. That is why performic is often preferred as formic acid IS strong enough to self-catalyze peracid formation.

 

[OrgUnikum]

P2P and strong bases do not go well together, the P2P tends to self-condense and polymerize into the infamous red tar. Using a HUGE amount of base/alcohol by volume is the only way I can think of to avoid this to happen excessively. If the P2P is less concentrated there is less opportunity to self-condense. Also I say avoid local spots of higher concentration by dripping in slowly under very good stirring. Never underestimate the plain mechanical factors like concentration, stirring etc. - it is half the rent.

 

[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.

 

[Cbison]

My crystal liquifies at room temperature, how do I solve this problem

 

[Fenster]

D
DCM has a dipole moment. It is polar albeit slightly.

Are you sure your a chemist? I don't mean to be rude but DCM is not an NPS in the traditional sense.

Can I ask, have you or your team performed this method in totality?

 

[TheNut22]

I use little bit of ethyl acetate (dipole almost same as DCM) and xylene, and it works like a charm.

 

[Mo0odi]

Is there an alternative to peroxide hydrogen ?

 

[Ortist]

Original twodogs procedure uses perboric acid made in-situ from acetic acid & sodium perborate. Perboric route is a bit messy and requires filtering

 

[TheNut22]

I used one time performic acid, and it worked, but not as well as peracetic acid.

 

[billythekid]

per boric and GAA makes peracetic

 

[TheNut22]

10 g benzaldehyde + 24 g MEK + 28 g hydroc.acid (~20%) = 28 g of crystals, dried in pyrex dish = 13 g of crystals.
Just keep it simple. When you are done heating, extract the brown organic layer. Wash with 40 ml of water. Extract again. Put 20 ml:s of 10% KOH-solution in. Get rid of the water. Check pH. If too acidic, or too basic, put it to 7. Get rid of the water again. Put it in freezer, because you can then, when frozen, pour the oily shit away, and get almost white crystals. Put the crystals in pyrex dish, or something and dryi it. It can liquify, but no problem. Just heat, freeze, heat, freeze, you dry those crystals, but they cannot be crispy dry. Don't know why. Maybe they are just like that.

 

[TheNut22]

But there is one odd thing. When I don't measure pH-level at all, and just put those white crystals in my measuring flask in freezer, I get double amount of pure white crystals. Today, I made almost same amount of reagents, and same way, BUT I titrated the pH-level to 7, I got just half of the crystals. I think there is something to this. Now in the evening I just put those lame 20 ml:s of crystals in freezer, and they are orange! half of it looks like might get just oil, but I just checked there is some kind of reaction between the orange solution and upper layer white crystals that have appeared in about 10 minutes. I have come to conclusion that when you do the aldol with acid and you get basic crystals and don't titrate the pH-level at all, you get double or triple amount of Methylphenylbutenone, and when it is overnight in freezer, you dump the oil in the upper layer, and thats it. So, from now on, I don't recommend the pH-level titration.

P.S I'm sorry, I made some Methcathinone today and I'm so tired, so I'm sorry for the unclear text.
Going to sleep now.

 

[Cbison]

When you say u wouldn’t titrate any more does it mean no more hydroxide wash after the MEK + Benzaldehyde reaction. Will it result in more quantities of MPB?

 

[TheNut22]

When I extracted my P2P with ethyl acetate, I put little bit of drying agent in, and put it in my fridge.
I looked the liquid, and when it was about 3 hours i the fridge, the bottom layer was full of clear oil.
Is that my P2P? Can I really extract with this way?!

 

[TheNut22]

I was just water in the bottom. But my P2P was in the ethyl acetate.

 

[TheNut22]

When I did the Leuckart reaction in 32 hours, I got about 11 grams of n-formyl --- .
I hydrogenated it over 2 hours in KOH solution at reflux temperature. I got about 7 grams of A oil.

 

[OrgUnikum]

P2P is very well soluble in EtOAc - Ethyl Acetate. It is also soluble in Benzene, Toluene, Xylene, Ether, DCM but it is only sparingly soluble in Naphta aka Shellsol aka Wundbenzin/Reinigungsbenzin. A mixture of Ethyl Acetate and Naphta 50/50 works great.

 

[TheNut22]

I read some "data" some time ago that it is just sparingly soluble in ethyl acetate. OK. Thanks.
But now I'm good. Thank you OrgUnikum for your reply also for my P2P hydrogenation. Now it went very well, with putting more solution to the base, in acetoxyphenylpropene hydrogenation. I got yellow, very "honey-like" smelling solution in xylene. This is the first time the solution is not red, because I followed your instructions to put more solution. Thanks!