Phenylacetone (P2P) synthesis from benzaldehyde with butanone

[WillD]

Reagents:​

• Benzaldehyde 1000 g;​
• Methyl ethyl ketone (MEK) 1000 ml;​
• Distilled water 14.5 L;​
• Chloroform (CHCl3) 7.6 L;​
• Sodium bicarbonate solution (NaHCO3);​
• Magnesium sulphate (Na2SO4) anhydrous;​
• Glacial acetic acid 10 L;​
• Hydrogen peroxide (H2O2) 1300 g 50 %;​
• Sodium hydroxide (NaOH) 600 g;​

Equipment and glassware:​

• 5 and 10 L Round bottom flasks;​
• Water bath;​
• HCl gas source;​
• 25-30 L Batch reactor with reflux condenser and heating system;​
• Vacuum source;​
• Glass rod and spatula;​
• Rotovap machine (optional);​
• pH indicator paper;​
• Laboratory scale (1-1000 g is suitable);
• Measuring cylinders 1000 mL;
• 1000 mL x3; 2000 mL x3; 5000 mL x3 Beakers;
• Several buckets;

Step 1. 3-Methyl-4-phenyl-3-buten-2-one synthesis (cas 1901-26-4).
1. Benzaldehyde 1000 g and methyl ethyl ketone (MEK) 1000 ml are mixed in 5 L flask, stirred and chilled at 0 °C.
2. HCl gas is bubbled slowly through the mixture for a 1.5 h.
3. The solution is stirred for addition 1.5 h at room temperature.
4. Distilled water 2 L is added. The solution is extracted with chloroform (CHCl3) 800 ml x2, then the extract is washed with sodium bicarbonate solution (NaHCO3) to neutral pH and dried over magnesium sulphate (MgSO4).
5. Solvent is evaporated under vacuum and 3-methyl-4-phenyl-3-buten-2-one (cas 1901-26-4) is distilled under vacuum (b.p. 269.6±9.0 °C at 760 mm Hg). Reaction yield is 1000 g.​

​

Step 2. 2-Acetoxy-1-phenyl-1-propene (cas 24175-87-9) synthesis.

1. 3-Methyl-4-phenyl-3-buten-2-one (cas 1901-26-4) 1 kg from Step 1, glacial acetic acid 10 L and hydrogen peroxide (H2O2) 1300 g 50 % are poured into a 25-30 L batch reactor with reflux condenser, stirred and at 55 °C for 23 h.
2. Next, distilled water 10 L is added.
3. The reaction mixture is extracted with chloroform 5 L and dried over magnesium sulphate (Na2SO4).
4. Solvent is evaporated under vacuum. 2-Acetoxy-1-phenyl-1-propene (cas 24175-87-9) yield is 800 g.​

Step 3. 1-Phenyl-2-propanone (P2P; cas 103-79-7).

1. 2-Acetoxy-1-phenyl-1-propene (cas 24175-87-9) 800 g from Step 2 and sodium hydroxide (NaOH) 600 g in distilled water 2500 ml is stirred at 50 °C for 12 h in 10 L flask with reflux condenser.
2. Reaction solution is extracted with chloroform 1000 ml, dried over magnesium sulphate (Na2SO4) and the solvent is evaporated under vacuum. 1-Phenyl-2-propanone yield is 650 g.​

 

[Jack]

Sci-Hub | The Synthesis and Investigation of Impurities found in Clandestine Laboratories: Baeyer-Villiger Route Part I; Synthesis of P2P from Benzaldehyde and Methyl Ethyl Ketone | 10.1016/j.forsciint.2016.03.034

 

[cyb3r0]

Thank you for the explanation. Please mention the required materials that you knew
benzaldehyde and Methyl Ethyl Ketone ( MEK )
Is this all that is required?
Thank you

 

[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.

 

[lalalander]

Did you use 50/50 water/alcohol or just water and base?

 

[TheNut22]

Alcohol/water with base.

 

[TheNut22]

It's worth looking in different online stores or normal street stores that sell H2O2 for growing plants.

 

[Jack]

It is not a catalyst it is an oxidant please read the link provided, search up baeyer villiger oxidation.

 

[MadHatter]

Ok, good, an oxidant. And I see the reaction in the link. Thank you! In it they use sodium perborate for the BV- oxidation. That might be more accessible. I guess piranha solution could be used also? What other candidates are there?

 

[MadHatter]

After reading up a bit: how about sodium percarbonate? Would that suffice? Because if it would, this synthesis would become much more OTC. And definately worth the time to calculate the molar ratio.

 

[WillD]

Approximately 3kg percarbonate for this reaction+water. Find a concentrated peroxide is best choice.

 

[MadHatter]

That's perfectly doable. Of course it's second best, but hydrogen peroxide in concentrations above 3% is a strictly controlled substance nowadays in most of EU.
One thought though: wont the carbonate ion react really vividly with the acetic acid? And maybe neutralize it?

 

[Rabidreject]

Look at hydroponic ph+ solution - it is 35% I am from the UK. Dunno if that would suffice but those are how I get my hydrogen peroxide and my 35% sulphuric acid also tbf! Very useful for multiple applications in my life!

 

[WillD]

maybe can buy ready peracetic acid, and use it for complete reaction without acetic acid and H2O2

 

[Mo0odi]

How do we use peracetic acid? Is there an explanation?

 

[Hans-Dietrich]

it would be logical to reflect this method in the initial post.

 

[Jamroz]

Is it necessarliy to make it under vacum destilation or normal pressure destilation will be enought ? Could you expand first step in the reaction hcl gas bubbled in mixture

 

[WillD]

Possible
here (click)

 

[n00by Blitz]

Just to confirm. It is: 10 liters of glacial acetic acid. Am I correct?

 

[WillD]

yes, 10L of GAA

 

[situ1988]

What concentration of GAA

 

[waltjr5858]

Just by 99% pure GAA from anywhere and that's what you use

 

[n00by Blitz]

Is it OK to use a plastic drum or PVC pipe for this part?

 

[a_king]

is it possible to replace chloroform?

 

[Waspamine]

yh I know 2 yrs late but yh, so chloroform is really easy to synth, look up some on ytb you'll see

 

[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.

 

[waltjr5858]

Toulene is perfectly fine also

 

[MadHatter]

BTW, why such ENORMOUS quantities of GAA and H2O2? Is it possible to use less? What are their roles in this reaction?

 

[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]

My first try to do performic acid oxidation of MPB, to do it now better.
My MPB doesn't really mix to formic acid, as I put it in formic acid solution, buffered it with sodium carbonate, so
do I need a solvent for my MPB? If I do, can I use ethanol, or is acetone better? OrgUnikum? Someone? MadHatter?
I'll be VERY thankful because I don't want to mess up my reaction now, and I can give some tips for the procedure if it goes, and works well. AND, I don't have DCM... I haven't put it yet in the performic acid.

 

[TheNut22]

Or, can I use glacial acetic acid as the solution for my MPB also with my performic acid?

 

[ByHyde]

I've been working on this synthesis for a long time. I work with sodium perborate and synthesize sodium perborate myself. And break it into pieces, spreading the oxidation over 12 hours.
1 GR MPT= 3.5 ML GAA +2.5 GR PSB+2 ML ACETONE I hope good days are near.