Phenylacetone (P2P) synthesis from benzaldehyde with butanone

[Phoneix73]

Solvent evaporated, can normal vacuum be used or what is the method?

 

[Fenster]

Solvent evaporated, can normal vacuum be used or what is the method?

Phoneix73270C is very high to distil without glassware.

 

[Phoneix73]

distilled or evaporated under vacuum, at what temperature is it heated, evaporated or distilled? and how many hours will it be distilled

 

[Fenster]

The reference is 270C as the boiling point. I do wonder if the solvent can be removed and just use it as is in step 2.

 

[Fenster]

I need help!

100g of both Benzaldehyde and MEK were added to a 500ml RBF and chilled to zero. The mixture was put on mag Stir and HCL was bubbled through the solution, quickly at first and then slow and steady once the HCl generator was fine tuned. (HCl over Conc. Sulphuric Acid). The solution turned yellow, then red, followed by very dark red. After 1.5 Hours, gas was removed and let stir at room temperature for 1.5 hours. Added 200ml of distilled water, instantly two layers formed. A dark layer (organic bottom) and a aqueous layer clear yellow. 40ml of DCM was added to the solution.

Here is my problem. The DCM appears to have merged with the organic layer. It's a lovely smelling camphur solution, actually it's a beautiful smell. However I cannot see the DCM layer in the sep funnel. Damn, how the fuck to resolve this?

 

[Fenster]

So I separated and did a DCM extraction on the Aqueous phase. Nothing was left after evaporation of DCM. I'm thinking I'm going to have to distill everything in the organic phase and see whats left over as a solid.

This is a real pain, has anyone done this synth successfully? Can anyone tell me if DCM is the issue. I don't want to make Chloroform or buy it

 

[Fenster]

@William Dampier have you run this synth?

Any help would be much appreciated.

 

[Fenster]

Unfortunately my glass thermometer broke, so I couldn't read off the fractions. Managed to pull a clear layer of what smells like DCM and HCL. I changed over to an oil bath and got over smoke temp of veg oil around 220, switched on vacuum and pulled a pale yellow oil over. It's an effort without short path to bring the column up to such a high temp. I figure I was pulling over around 200.

I don't think the oil is going to crystallise so I think next step will be DCM extract on the distillate.

 

[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.

 

[Fenster]

Aldol Condensation.

The directions for this are in Organic Reactions

200 gms of Benzaldehyde and 300 gms of Methyl Ethyl Ketone are mixed in a 1 litre beaker and cooled below 5°C. HCl gas is bubbled through until 40gms has been added. The mixture goes from a clear solution to a red colour and becomes turbid so that you can't see through it. The mixture is kept over night and becomes a brown colour. It is washed with water and then 10% NaOH solution, the organic layer seperated and distilled. At 240°C a yellow oil comes accross and the temperature gradually rises to 260°C.

The oil can be crystalized by cooling in the freezer overnight. This in itself does not induce crystalization but if you also put a spoon in the freezer and then dip it in and out of the cool mixture you get some seed crystals that induce crystalization. The mass turns from an orange oil to sulfur coloured crystals, mp 38°C, 180 gms (Methyl Phenyl Butenone.

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]

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.

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

 

[Cbison]

I put the whole thing with liquid and crystals to pyrex dish and little bit 96% ethanol and heat it, so all the material goes to liquid form. When the ethanol boils, it removes extra water from the mixture. Then I put it back in freezer in 100 ml measuring flask. Let it stay in the measuring flask in freezer from a day.
All the side products (dark liquid) is then in upper layer, and I pour it down the drain. Then I heat the flask little bit and almost always there will form a water layer at the bottom of the measuring flask. I suck the water out with my pipette, and put it again in the freezer for about a day again. It will form side product oil again in the upper layer. Down the drain again. Now you should have crystals that don't liquify in room temperature. It goes maybe little bit like goo, but it is what it is.

TheNut22So heat is applied to boil off excess solvent then allowed to cool for crystallization to occur. Do you think one can proceed to Baeyer villager reaction without crystallization MPB?

 

[TheNut22]

So heat is applied to boil off excess solvent then allowed to cool for crystallization to occur. Do you think one can proceed to Baeyer villager reaction without crystallization MPB?

CbisonYou can also distill it from your solution mix. Someone said, just distill away all that distills 150 C and under, and throw them away. Methylphenylbutenone distills around 270-300 C at normal pressure. And you can use that yellow coloured oil in Baeyer-Williger, that is same MPB, but in different form. I haven't done that, but also my crystals will become slurry in here. It is summer, and the melting point is around 13-14 C. If my apartment temp is around 22 C, so ...

 

[Fenster]

I put the distillete in the freezer over night, nothing happened, I dipped a frozen spoon into the mix and it instantly crystalized. Quite extraordinary. I'll move onto step 2.

 

[Fenster]

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 %

Why is the first two reactants quoted in MLS, and the H2O2 is quoted in grams. Another point if confusion in this write up.

 

[Fenster]

3. The reaction mixture is extracted with chloroform 5 L and dried over magnesium sulphate (Na2SO4).

Can someone please explain, how extraction with Chloroform works when the product is not in the Aqueous phase. Your Chloroform will merge with the organic layer, and you will have 1 phase.

What this should read-

Rx is washed with distilled water X3 then washed 3x with Sodium Bicarbonate. The organic layer is put into simple short path distillation an collected between 220 and 260. The distillete will be a yellow coloured oil. The oil is put into the freezer with a cold stainless spoon and frozen overnight. To initiate crystalization the spoon is dipped into the solution until crystalization begins.

 

[Fenster]

2.2.5. 2-Acetoxy-1-phenyl-1-propene 4 (Baeyer–Villiger reaction
using SARD-Oxy plus)
SARD-oxy plus (3 g, 2–6 mmol of sodium percarbonate) was
added portion-wise over 6 h to a mixture of 3-methyl-4-phenyl-3-
buten-2-one 3 (0.5 g, 3 mmol), glacial acetic acid (7 mL, 0.122 mol),
at 55 8C. The solution was heated under reflux at 55 8C for a total of
24 h. Upon cooling to room temperature, brine was added followed
by extraction with chloroform, which was then washed with brine.
The organic solution was dried (Na2SO4) and the solvent removed
under vacuum. Yield 43% based on 1
H NMR.2

This may prove useful to some for step 2.

Using a common OTC laundry oxidation powder resulted in the baeyer villager reaction success with a yield of 43%.

 

[Fenster]

1-Phenyl-1-penten-3-one 8
NaOH solution (10 mL, 2 M) was added to a mixture of
benzaldehyde (4 g, 39 mmol) and MEK (2.8 g, 39 mmol) and the
resulting solution stirred at room temperature overnight. The
solution was extracted with chloroform, dried (Na2SO4) and the
solvent removed under vacuum. The residue was purified by
distillation (90 8C, 0.1 mmHg) with the resulting oil solidifying
after one day (m.p. 40–41 8C). Yield 50%.

Variation to step 1.

If you are having trouble generating stable dry HCL it seems you can just use NaOH and stir overnight. Yields are lower but your not dealing with the hassle of generating HCL gas.

 

[Phoneix73]

Variation to step 1.

If you are having trouble generating stable dry HCL it seems you can just use NaOH and stir overnight. Yields are lower but your not dealing with the hassle of generating HCL gas.

Fensterso how many degrees do we distill in the last step

 

[Fenster]

C

so how many degrees do we distill in the last step

Phoneix73Can you be specific?

The thermometer was broken, but to distill:
1-methyl-4-fenyl-3-Buten-2-one It was very hot. Without short path distillation and only a 40cm fractional column. It is such a pain to get that to come over even with a vacuum. an oil bath with vegetable oil at smoke temp cleared a clear liquid that was very HCl saturated, and also the DCM that failed to separate. I turned on vacuum and pulled a thin yellow oil above 200. The distillation flask becomes very thick before you can pull it all over. You can read about xtal formation in my earlier posts.

After the oxidation there was no more need for Distillation but you need to make a separation plan early. Even on a <50g scale there is a lot of liquid to extract from. The DCM in this step works really well as you can decant most of the liquid off and then use a sep funnel to get the DCM layer. Unfortunately my vacuum pump broke so I had to try evap the solvent without vacuum. It's possible but I don't recommend. The volatiles coming off with the DCM are not nice at all. I ended up pouring the last if the DCM into a Pyrex tray and let evap over night. So that adds a whole day into an already 3 day process.

 

[Phoneix73]

C

Can you be specific?

The thermometer was broken, but to distill:
1-methyl-4-fenyl-3-Buten-2-one It was very hot. Without short path distillation and only a 40cm fractional column. It is such a pain to get that to come over even with a vacuum. an oil bath with vegetable oil at smoke temp cleared a clear liquid that was very HCl saturated, and also the DCM that failed to separate. I turned on vacuum and pulled a thin yellow oil above 200. The distillation flask becomes very thick before you can pull it all over. You can read about xtal formation in my earlier posts.

After the oxidation there was no more need for Distillation but you need to make a separation plan early. Even on a <50g scale there is a lot of liquid to extract from. The DCM in this step works really well as you can decant most of the liquid off and then use a sep funnel to get the DCM layer. Unfortunately my vacuum pump broke so I had to try evap the solvent without vacuum. It's possible but I don't recommend. The volatiles coming off with the DCM are not nice at all. I ended up pouring the last if the DCM into a Pyrex tray and let evap over night. So that adds a whole day into an already 3 day process.

Fenster

use this kind of stud thermometer

 

[Phoneix73]

i also had a thermometer, so it was divided in half, it was very funny

 

[TheNut22]

i also had a thermometer, so it was divided in half, it was very funny

Phoneix73I was on phone, and I looked at my new equipment. I just took it and *snap!*. Oh, it was my new thermometer. It WAS.

 

[Fenster]

Are you using Distillation glassware or just jars?