# 1-Phenyl-2-propanone (P2P) synthesis from Diethyl(phenylacetyl)malonate



## G.Patton

*Introduction*​This is one of the simplest ways to obtain 1-Phenyl-2-propanone (P2P). Diethyl(phenylacetyl)malonate can be bought in some web market quite easy or synthesized by yourself using this method. Also, you can learn other P2P synthetic paths in our forum by following links: Synthesis of P2P from benzaldehyde with MEK, Synthesis of P2P by oxidation of alpha-methylstyrene with Oxone, Phenylacetone (P2P) syntheses via Grignard reagents, Industrial phenylacetone (P2P) production from benzene, Synthesis of P2P from P2NP with NaBH4 via K2CO3/H2O2 system.

*Difficulty Rating:* 3/10​




​*Equipment and **glassware:*​
500 mL round bottom flask;
Reflux condenser;
Boiling chips;
Retort stand and clamp for securing apparatus;
1 L Separatory funnel;
Vacuum distillation setup;
Water bath and ice;
Heating plate;
100 mL x3; 250 mL x2 Beakers;
pH indicator paper;
Rotovap machine;
Vacuum source;
Laboratory scale (0.01-100 g is suitable);
Measuring cylinder 10 mL and 100 mL.
*Reagents:*​
Phenylacetylmalonate *(1)* 48.5 mL (55.66 g, 0.20 mole) [Diethyl(phenylacetyl)malonate; cas 20320-59-6];
Glacial acetic acid (AcOH) 60 mL;
Concentrated sulfuric acid (H2SO4) 7.5 mL;
Distilled water ~240 mL;
Sodium hydroxide (NaOH) solution 20 % ~100 mL;
Diethyl ether (Et2O) ~150 mL;
Sodium sulfate (Na2SO4) anhydrous ~100 g;
Drierite ~50 g (optional).
*Procedure*​To a diethyl phenylacetylmalonate *(1)* 48.5 mL (55.66 g, 0.20 mole) was added a solution of 60 mL of glacial acetic acid, 7.5 mL of concentrated sulfuric acid and 40 mL of water, and the mixture refluxed in 500 mL round bottom flask with reflux condenser for four or five hours until the decarboxylation was complete. The reaction mixture was chilled in an ice-bath, made alkaline with 20 % sodium hydroxide solution, and extracted in a separatory funnel with several portions of ether (~3 x 50 mL). The combined ethereal extracts were washed with water (~200 mL), dried with anhydrous sodium sulfate (Na2SO4) followed by Drierite (optional), and the solvent distilled off. The residue containing the ketone *(2)* was distilled in vacuo to give 1-Phenyl-2-Propanone *(2)* in 71 % yield (b.p. 97-98.5 °C/13 mmHg, 214-215 °C/760mmHg).​

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## btcboss2022

I made this process with success! 
We are just trying to fix a small problem with salt precipitate in the alkalination phase.
I'm very grateful to G.Patton for all his help great expert thanks again.








photo-2022-05-04-14-24-05


Image photo-2022-05-04-14-24-05 hosted in ImgBB




ibb.co












photo-2022-05-04-14-24-09


Image photo-2022-05-04-14-24-09 hosted in ImgBB




ibb.co












photo-2022-05-06-12-53-27


Image photo-2022-05-06-12-53-27 hosted in ImgBB




ibb.co


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## btcboss2022

We are practically sure that the precipitate is Sodium acetate salt from the acetic acid, any idea to avoid it or solve it? 
Because in big scale would be a problem.
Thanks.


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## G.Patton

btcboss2022 said:


> We are practically sure that the precipitate is Sodium acetate salt from the acetic acid, any idea to avoid it or solve it?



btcboss2022It could be NaSO4 as well. The best solubility in water has MgSO4. If you have MgOH2, you can try to substitute NaOH.
MgSO4 has 35,1 g/100ml at 20deg
Na2SO4 has 19,2 g/100 ml at 20
K2SO4 has 11.1 g/100 ml at 20


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## btcboss2022

G.Patton said:


> It could be NaSO4 as well. The best solubility in water has MgSO4. If you have MgOH2, you can try to substitute NaOH.
> MgSO4 has 35,1 g/100ml at 20deg
> Na2SO4 has 19,2 g/100 ml at 20
> K2SO4 has 11.1 g/100 ml at 20



G.PattonOk we will try it and update you, anyway there is another problem the oil yield is very low and I think I know why could be:

In reflux step must be an intermediary product that boils around 75-80C so the mixture don't goes up this temp, if you heat more you will lose product by the condenser.
Acetic acid boils at 118C
Water at 100C
20320 at 120C
Sulphuric at 337C 
So only an intermediary product can be boiling and refluxing at this temp, in my opinion this low temp don't allow to make the reaction properly for this reason the low yield.
We are thinking changes to improve that but is hard to believe that with this exactly method you can get 71% yield for the reasons explained before.
Thanks.


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## btcboss2022

btcboss2022 said:


> Ok we will try it and update you, anyway there is another problem the oil yield is very low and I think I know why could be:
> 
> In reflux step must be an intermediary product that boils around 75-80C so the mixture don't goes up this temp, if you heat more you will lose product by the condenser.
> Acetic acid boils at 118C
> Water at 100C
> 20320 at 120C
> Sulphuric at 337C
> So only an intermediary product can be boiling and refluxing at this temp, in my opinion this low temp don't allow to make the reaction properly for this reason the low yield.
> We are thinking changes to improve that but is hard to believe that with this exactly method you can get 71% yield for the reasons explained before.
> Thanks.



btcboss2022Hello,

Any idea to change something to allow more temp in the reaction? We need a mixture that don't create an intermediate product of low boiling temp.
Thanks.


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## G.Patton

btcboss2022 said:


> Hello,
> 
> Any idea to change something to allow more temp in the reaction? We need a mixture that don't create an intermediate product of low boiling temp.
> Thanks.



btcboss2022increase pressure in the system


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## btcboss2022

btcboss2022 said:


> I made this process with success!
> We are just trying to fix a small problem with salt precipitate in the alkalination phase.
> I'm very grateful to G.Patton for all his help great expert thanks again.
> 
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> photo-2022-05-04-14-24-05
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> Image photo-2022-05-04-14-24-05 hosted in ImgBB
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> ibb.co
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> photo-2022-05-04-14-24-09
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> Image photo-2022-05-04-14-24-09 hosted in ImgBB
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> ibb.co
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> photo-2022-05-06-12-53-27
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> Image photo-2022-05-06-12-53-27 hosted in ImgBB
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> ibb.co



btcboss2022Pics were deleted, added again:


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## William Dampier

Yes, it looks like the truth. Share the other successes with this oil in the future.


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## btcboss2022

Ok in all the test I have done sometimes the mixture turns yellowish transparent in one single layer:


https://anopic.us/SwA2AN3mtVGbAmQaFCiZLFmyM7TIBPDKLVrVxSTz.jpg


And sometimes it get yellowish but not transparent and it has 2 different layers.
Is very strange because nothing different or changed in them.
What is sure is that 20320 in the mixture creates an intermediate product that is Ethyl acetate, this product has a low boiling temp and don't allow the mixture to get more than 80C we are thinking to distill it but not easy to choose in what moment exactly do it because it possibly helps in the reaction in some moments.
Another sure thing is that 20320 turns solid when it turns alkali over 8-9ph so because in the basification step , this solid can be solved in acid again if it appears, is totally different to the solid that appears after add alkali.
We will continue making tests and changes to improve it.
Thanks,


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## SpeeD

Can simple vacuum distillation be used instead of vacuum distillation?


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## G.Patton

SpeeD said:


> Can simple vacuum distillation be used instead of vacuum distillation?



SpeeDDo you understand your question?  Do you mean simple distillation instead of vacuum one? You can, 216 deg C is boiling point at normal conditions.


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## SpeeD

Can simple distillation+vacuum replace a rotary evaporator?



G.Patton said:


> Do you understand your question?  Do you mean simple distillation instead of vacuum one? You can, 216 deg C is boiling point at normal conditions.



G.Patton


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## G.Patton

SpeeD said:


> Can simple distillation+vacuum replace a rotary evaporator?



SpeeDYes, it can. Processes are same.


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## Costa

G.Patton said:


> *Introduction*​This is one of the simplest ways to obtain 1-Phenyl-2-propanone (P2P). Diethyl(phenylacetyl)malonate can be bought in some web market quite easy or synthesized by yourself using this method. Also, you can learn other P2P synthetic paths in our forum by following links: Synthesis of P2P from benzaldehyde with MEK, Synthesis of P2P by oxidation of alpha-methylstyrene with Oxone, Phenylacetone (P2P) syntheses via Grignard reagents, Industrial phenylacetone (P2P) production from benzene, Synthesis of P2P from P2NP with NaBH4 via K2CO3/H2O2 system.
> 
> *Difficulty Rating:* 3/10​View attachment 4670View attachment 4672​*Equipment and **glassware:View attachment 4673*​
> 500 mL round bottom flask;
> Reflux condenser;
> Boiling chips;
> Retort stand and clamp for securing apparatus;
> 1 L Separatory funnel;
> Vacuum distillation setup;
> Water bath and ice;
> Heating plate;
> 100 mL x3; 250 mL x2 Beakers;
> pH indicator paper;
> Rotovap machine;
> Vacuum source;
> Laboratory scale (0.01-100 g is suitable);
> Measuring cylinder 10 mL and 100 mL.
> *Reagents:*​
> Phenylacetylmalonate *(1)* 48.5 mL (55.66 g, 0.20 mole) [Diethyl(phenylacetyl)malonate; cas 20320-59-6];
> Glacial acetic acid (AcOH) 60 mL;
> Concentrated sulfuric acid (H2SO4) 7.5 mL;
> Distilled water ~240 mL;
> Sodium hydroxide (NaOH) solution 20 % ~100 mL;
> Diethyl ether (Et2O) ~150 mL;
> Sodium sulfate (Na2SO4) anhydrous ~100 g;
> Drierite ~50 g (optional).
> *Procedure*​To a diethyl phenylacetylmalonate *(1)* 48.5 mL (55.66 g, 0.20 mole) was added a solution of 60 mL of glacial acetic acid, 7.5 mL of concentrated sulfuric acid and 40 mL of water, and the mixture refluxed in 500 mL round bottom flask with reflux condenser for four or five hours until the decarboxylation was complete. The reaction mixture was chilled in an ice-bath, made alkaline with 20 % sodium hydroxide solution, and extracted in a separatory funnel with several portions of ether (~3 x 50 mL). The combined ethereal extracts were washed with water (~200 mL), dried with anhydrous sodium sulfate (Na2SO4) followed by Drierite (optional), and the solvent distilled off. The residue containing the ketone *(2)* was distilled in vacuo to give 1-Phenyl-2-Propanone *(2)* in 71 % yield (b.p. 97-98.5 °C/13 mmHg, 214-215 °C/760mmHg).​View attachment 4671​



G.PattonHi,

COuld anybody answer some doubts? 

1.- the alkalinization with NaOH 20%, which is the ph target?
2.- For the extraccion, could I use dichloromethane instead of diethyl ether? 
3.- Which layer do I have to extract with several portions of ether (~3 x 50 mL)?
4.- What is "The combined ethereal extracts" refers to?


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## G.Patton

Costa said:


> 1.- the alkalinization with NaOH 20%, which is the ph target?



CostaHello, alkaline is pH 12


Costa said:


> 2.- For the extraccion, could I use dichloromethane instead of diethyl ether?


I think yes


Costa said:


> 3.- Which layer do I have to extract with several portions of ether (~3 x 50 mL)?


Layer with P2P (oily)


Costa said:


> 4.- What is "The combined ethereal extracts" refers to?


(~3 x 50 mL)? - Each portion of sequential extraction 50 + 50 + 50 mL are combined. Read about Extraction in Lab FAQ section.


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## Costa

Thanks! just one more... concerning question 3 (extraction with ether), how is it made? I mean, I have to take off the oily layer (with P2P) and add the ether to the other layer in order to extract from there the interesting compound (P2P), is that correct?


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## G.Patton

Costa said:


> Thanks! just one more... concerning question 3 (extraction with ether), how is it made? I mean, I have to take off the oily layer (with P2P) and add the ether to the other layer in order to extract from there the interesting compound (P2P), is that correct?



Costa*>>>Read about Extraction in Lab FAQ section.*
Just add solvent to the reaction mass as described in manual and carry out the extraction.


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## Zetetic

G.Patton said:


> *Introduction*​This is one of the simplest ways to obtain 1-Phenyl-2-propanone (P2P). Diethyl(phenylacetyl)malonate can be bought in some web market quite easy or synthesized by yourself using this method. Also, you can learn other P2P synthetic paths in our forum by following links: Synthesis of P2P from benzaldehyde with MEK, Synthesis of P2P by oxidation of alpha-methylstyrene with Oxone, Phenylacetone (P2P) syntheses via Grignard reagents, Industrial phenylacetone (P2P) production from benzene, Synthesis of P2P from P2NP with NaBH4 via K2CO3/H2O2 system.
> 
> *Difficulty Rating:* 3/10​View attachment 4670View attachment 4672​*Equipment and **glassware:View attachment 4673*​
> 500 mL round bottom flask;
> Reflux condenser;
> Boiling chips;
> Retort stand and clamp for securing apparatus;
> 1 L Separatory funnel;
> Vacuum distillation setup;
> Water bath and ice;
> Heating plate;
> 100 mL x3; 250 mL x2 Beakers;
> pH indicator paper;
> Rotovap machine;
> Vacuum source;
> Laboratory scale (0.01-100 g is suitable);
> Measuring cylinder 10 mL and 100 mL.
> *Reagents:*​
> Phenylacetylmalonate *(1)* 48.5 mL (55.66 g, 0.20 mole) [Diethyl(phenylacetyl)malonate; cas 20320-59-6];
> Glacial acetic acid (AcOH) 60 mL;
> Concentrated sulfuric acid (H2SO4) 7.5 mL;
> Distilled water ~240 mL;
> Sodium hydroxide (NaOH) solution 20 % ~100 mL;
> Diethyl ether (Et2O) ~150 mL;
> Sodium sulfate (Na2SO4) anhydrous ~100 g;
> Drierite ~50 g (optional).
> *Procedure*​To a diethyl phenylacetylmalonate *(1)* 48.5 mL (55.66 g, 0.20 mole) was added a solution of 60 mL of glacial acetic acid, 7.5 mL of concentrated sulfuric acid and 40 mL of water, and the mixture refluxed in 500 mL round bottom flask with reflux condenser for four or five hours until the decarboxylation was complete. The reaction mixture was chilled in an ice-bath, made alkaline with 20 % sodium hydroxide solution, and extracted in a separatory funnel with several portions of ether (~3 x 50 mL). The combined ethereal extracts were washed with water (~200 mL), dried with anhydrous sodium sulfate (Na2SO4) followed by Drierite (optional), and the solvent distilled off. The residue containing the ketone *(2)* was distilled in vacuo to give 1-Phenyl-2-Propanone *(2)* in 71 % yield (b.p. 97-98.5 °C/13 mmHg, 214-215 °C/760mmHg).​View attachment 4671​



G.PattonWhat are the replacement options?

Glacial acetic acid (AcOH) 60 mL;
Concentrated sulfuric acid (H2SO4) 7.5 mL;
Diethyl ether (Et2O) ~150 mL;
In stock:
acetic acid 70%

hydrochloric acid aqueous solution:
Compound
water, inhibited hydrochloric acid 5% or more, but less than 15%, non-ionic surfactants < 5%.

Isopropyl alcohol
Petroleum ether
Dichloroethane
Benzene
Toluene
Methylamine 38%

Any help please!?


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## Zetetic

Zetetic said:


> What are the replacement options?
> 
> Glacial acetic acid (AcOH) 60 mL;
> Concentrated sulfuric acid (H2SO4) 7.5 mL;
> Diethyl ether (Et2O) ~150 mL;
> In stock:
> acetic acid 70%
> 
> hydrochloric acid aqueous solution:
> Compound
> water, inhibited hydrochloric acid 5% or more, but less than 15%, non-ionic surfactants < 5%.
> 
> Isopropyl alcohol
> Petroleum ether
> Dichloroethane
> Benzene
> Toluene
> Methylamine 38%
> 
> Any help please!?



ZeteticHa-ha-h...
I seem to have a more serious problem.
Diethyl 2-phenylmalonate is sold, not Diethyl(phenylacetyl)malonate.
:-(


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## G.Patton

Zetetic said:


> Diethyl ether (Et2O) ~150 mL;



ZeteticHi, it can be replaced by Petroleum ether


Zetetic said:


> Glacial acetic acid (AcOH) 60 mL;


you can use acetic acid 70% but you have to recount volume of water


Zetetic said:


> Concentrated sulfuric acid (H2SO4) 7.5 mL;


you can't replace it


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## cokemuffin

Are there changes in the procedure if you use ethyl 3-oxo-4-phenylbutanoate (CAS 718-08-1)?


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## G.Patton

cokemuffin said:


> Are there changes in the procedure if you use ethyl 3-oxo-4-phenylbutanoate (CAS 718-08-1)?



cokemuffinFor 3-oxo-4-phenylbutyrate reaction is different.


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