Phenylacetone (P2P) synthesis from benzaldehyde with butanone

[MadHatter]

Thank you so much for the easy and detailed synth description!
How about the hydrogen peroxide, could that be substituted? It's a really controlled chemical nowadays, and a bitch to synthesize yourself. Its mainly there as a catalyst in the reaction between the glacial acetic acid and the 3-methyl-4-phenyl-3-buten-2-one, right? What could be a good substitute?

 

[handle]

Peracids will work (lower yields) Baeyer-Villiger oxidation.read the investigation paper above.

 

[TheNut22]

Alcohol/water with base.

 

[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]

This is a VERY GOOD guestion! The saponification MUST be done, like dropping the base solution VERY SLOWLY in the acetoxy! Now, when I dropped the base solution in two hours with syringe, I got the first P2P!
Other times, I just dropped the whole base liquid into acetoxy and started shaking violently... xD THAT was my failure.

 

[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]

So that was a complete failure. DCM dissolves straight into the yellow distillate.

Now I imagine Chloroform would behave the same way. This is really annoying.

 

[waltjr5858]

Use toulene Next time. Much cheaper and easier than chloroform. But yes these solvents should Mix right in with the yellow layer If you mean the organic layer Because they absolutely mix. Now if you're extracting from A water mix Toss some toulene On top And the oil Absolutely migrate over Then just distill off the toulene And reuse. The only way to extract A solvent From the organic layer Is too distill it off.

 

[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.

 

[waltjr5858]

That's pretty much perfect for personal use

 

[TheNut22]

 

[TheNut22]

28 g bitter almond aroma (1 bottle) + 22 g MEK + 30 g ~18% hydrochloric acid. 100°C degrees.
Time: 4 hours (my picture above is the result)

 

[TheNut22]

I'm getting new glassware next week, so I can start experimenting to next level.

 

[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

 

[waltjr5858]

The chloroform yields are horrible from bleach and would take forever to make a decent amount. Use toulene

 

[mithyl2]

what is the best way to make 50% Hydrogen peroxide?

does it have to be exactly 50%?

 

[skanderbeg]

YT tutorials on that and do your math with the % peroxide you have. Other than that buy from alfa aesar. Yes it's better to use 50% because it has a lot of water as a stabilizer/diluting agent and can (don't know for sure) interfere with the reaction.

 

[waltjr5858]

Yes as you boil it off you need to weigh the liquid on an accurate small scale and check the density until you get to 50%

 

[Ortist]

saponification in aqueous NaOH at 50 degrees ?! Thats really bad idea

 

[waltjr5858]

Yeah if you're going to write that's a bad idea you should probably explain why and the correct way with a reference if possible to help those out that are trying to accomplish it....

 

[lalalander]

Everyone says this method has flaws. Has anyone ever really gotten significant yields with this method?

 

[Ortist]

You can also distill P2P with water, but it is very slow. However you MUST distill methyl-phenyl-nutenone under vacuum because there is significant amount of crap and MPB will not distill with water

 

[waltjr5858]

Ya that should absolutely work but... that amount will probably be slightly different... maybe go by mols if they differ if not just use the amount listed with sodium. The sodium one is very easy to make though...

 

[waltjr5858]

Absolutely agreed LOL but I have found a way around the sodium ethyl sulfate method which works pretty good this way and if you're comfortable with working with diethyl sulfate and don't mind making a box to attach to a reciprocating saw as a shaking device that works pretty good also. But when you make your sodium Ethel sulfate follow all the normal ways to do it except use sodium hydroxide which I can give you a link to a big long procedure about some research they did about making sodium ethyl sulfate and at the end they will tell you to leave your Beaker standing for days to wait for the sludge to settle which to an extent you will have to but if you have a really good vacuum pump and you can pull a deep low vacuum then once you decant off the ethanol on top which will be pretty much clear you can distill very gently because sodium ethyl sulfate will decompose quickly at any temperature much higher than room temperature. Pull a deep ass vacuum and get rid of the ethanol leaving behind sodium ethyl sulfate. It's not the cheapest method because the alcohol should be anhydrous from the get-go 200 proof with no denaturing crap. Cost me about a hundred bucks for a gallon to test it out. But I can pull such a deep vacuum that the ethanol pretty much distilled off before I even applied Heat. Once I could see it get to the point of saturation I pretty much just let it dry from there. Using this method you will only get a half a mol of SES per 1 mol of concentrated sulfuric acid and 1.375 mol of ethanol. These are to be combined the acid and the ethanol below 20 Celsius at all times to prevent any side action from going on and once they're together toss it in the refrigerator for a minimum of 12 hours for the reaction to complete. Don't do any of that crap you see online about heating it to 140 or whatever. I have a link to the whole procedure that lays it out and it was thoroughly done just for sodium Ethyl sulfate. If you could make a large scale centrifuge I mean even a coke bottle hanging from a string and swing the damn thing over your head for a while you could get even a higher yield. But in the paper it will tell you exactly how much of an alcoholic solution of sodium hydroxide to use to neutralize the acid and create the sodium ethyl sulfate. This one just takes some patience and if you can put a hour or two a day into playing with it you could have enough to make plenty of nitroethane for at least personal play. I am absolutely sure of someone could scale the hell out of it but I just only mess around for personal use. I explained a little bit of it but if anyone wants the link ask and I will find it.

 

[waltjr5858]

I didn't realize how long that paragraph Was LOL but it was all voice to text if there's any errors blame it on Google

 

[TheNut22]

OK, and I didn't distill anything. Not MPB, acetoxy, or my P2P, but my downside was that I didn't do the saponification of acetoxy, right. No when I did it right, I got 13 g of dark orange P2P, that I washed a'la Uncle Fester. I got so clean P2P that I see through it. Annnd, it worked in my Leuckart with formamide plus ammonium formate catalyst, and ZnCl2-catalyst (it can be used). I have the better, AlCl3-catalyst for Leuckart, but I was thinking that have I made it wrong. So, with right purification (I purified my acetoxy also, and got clean very sweet smelling yellow oil. And, I read that PDF when they didn't distill P2P and tested the impurities, in P2P, there was impurities, but in VERY low amount.

I do not have even distilling apparatus anymore, because those cheap apparatus i bought, breaks very easily. For example, my magnetic stirrer broke, in my heating mantle, the first week, if I remember correctly. So, I have to buy one whole setup again. Now I have just erlenmeyer, broken glass stick, reflux column, and heating mantle. I also broke my 100 ml measuring flask. DAMN!

Can someone give me advise what kind of apparatus I have to buy to make the vacuum for distilling. I have vacuum holes in those glassses. And they are $24/40. What it means, I don't really know, I think that means the vacuum amount, or what?!

 

[Xiao hua]

even hcl has bubbled 1.5h.Why not add Hcl liquid? Why. Can someone explain me. Thanks

 

[Ortist]

You can use aqueous HCl. Just use 1 liter of benzaldehyde to 2 liters of MEK and calculated amount of 35..37% hydrochloric acid. You need 20g of PURE HCl per each 100g of benzaldehyde. So 1L of benzaldehyde will require 200g of PURE HCl. Now calculate how much aqueous acid do you need.

With gaseous HCl you'll get a bit better yeld and a bit less sideproducts. But in my opinion it doesn't worth it especially on big scale. Also with aqueous HCL you have to use more MEK otherwise your HCl will separate on the bottom too early.

"Gas for 1.5 hour" is WRONG. You have to gas until you get 20g of gas into each 100g of benzaldehyde. How long it can take nobody knows.

 

[waltjr5858]

correct...

 

[mckennai]

Can we correct something??? You saying magnesium sulphate anhydrous and giving Na2SO4 and one of the steps u saying mgso4 for it again.. Can you be clear for exact item and with exact values?? For usage and for buying.. We need to know amount that we need to get and use.. U didnt give any value for how much amount of that mgso4 or na2so4 we need... Thanks

 

[waltjr5858]

For the magnesium sulfate since it's just used for drying you can put in any amount you want really. There's not really a specified amount to put in but depending on the scale of what you're doing.... like if I was going to try something that was let's say 200 mils of oil or whatever you got I would probably toss 15 or a 20 G or so of magnesium sulfate in there and maybe steer it around for a little bit and an hour or so later come back and vacuum filter it right out of there. If the procedure you're doing has to be strictly anhydrous you could do the same thing over again maybe even three times if you want to make sure you get any and all water out of there. For this once is plenty

 

[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.

 

[TheNut22]

Now, when I have researched this aldol, I take back my words. This is important: Do not dump the oil, because the product is in the dark oil. Just keep the dark oil, when washing it 2-3 times with water. Then make 2,5% KOH-solution. Stirr it well, and the crystals will precipitate. Check the pH, and most of the time it is over 12. Drop some hydrochloric acid in, to make pH: 7. Almost always when the pH is seven, water layer forms in the bottom. If it doesnt, put little bit water, mix, and put it in the freezer for couple of hours. When it's frozen, I take it to room temperature, and when it's in room temp, I put the erlenmeyer to my stove, and heated softly, temp off from stove. Leave it for awhile, and wait until the water layer in the bottom of the flask is fully separated (it rises little bit) so I can get ALL of the water away with pipette. When this was done, I put it in freezer, took it out, and weighed it. Also it is good to dry those crystals with stove and larger cooking glass flask (what it is called..?). Just make plenty of those crystals, put it all in this wide glass thing (i'm tired), put little bit of alcohol on top and heat it gently. It will liquify. Just continue heating. When you want to, put it in freezer. Continue this thing couple of times, when the crystals don't melt in room temperature anymore. Done! I must sleep. tell me if I wrote something stupid, and you don't get it, you know... ---> zzZZzz

 

[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.

 

[TheNut22]

Now that I have over 100 grams of water and acid/base -purified, but wet MPB (collected from few reactions),
I'm going to dry the crystal solution into crystals, that don't melt in room temperature. I can post a picture of that, and I can post a picture of the acetoxyphenylpropene as well, with the yields.

 

[TheNut22]

I don't know why this picture went sideways, but you can see those bubbles in there, and
the cool colour what I get always in the peracetic oxidation process. The oxidation time was 24,5 hours.

 

[Labchef]

TheNuts22, did you react the MPB oil with peracetic acid without distilling it or obtaining the crystalline MPB salt.

 

[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.