# Synthesis of 3,4-methylendioxybenzylmethylketone from piperonal (glycide ester route)(small scale)



## William Dampier

*Step 1. PMK-glycidate.



*
1. Freshly prepared powdered sodium ethoxide (23 g.) was added during 4 hours to a stirred mixture of piperonal (50 g.) and ethyl a-bromopropionate (61 g.), cooled in ice-salt.
2. Stirring was continued overnight at room temperature and for 6 hours on the water-bath; ice-water was then added, and the mixture acidified with dilute acetic acid.
3. The glycide ester was extracted with ether, and ethereal solution washed with aqueous sodium carbonate and dried with sodium sulphate.
4. After removal of ether, the residue was distilled and collected between 70 *C and 200* at 20 mm.
5. Subsequent redistillation gave B-3,4-methylenedioxyphenyl-a-methylglycide ester (40 g.) b.p. 184-186*/14 mm (yield, 48%).


*Step 2. 3,4-methylendioxyphenylacetone.


*
1. The ether (35 g.) was refluxed for 5 hours with a solution of sodium hydroxide (10 g.) in 90% aqueous alcohol (150 ml).
2. After removal of part of the alcohol by distillation, the residue was diluted with a large volume of water and extracted with ether, and with the addition of a trace of copper powder;
3. The liquid was then distilled slowly under reduced pressure in the presence of copper powder. Redistillation of the product gave 3,4-methylenedioxybenzylmethylketone (11,1 g.) b.p 154-156/11 mm. (yield, 44.5%).


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## Jack

Sci-Hub | Methyl 3-[3′,4′-(methylenedioxy)phenyl]-2-methyl glycidate: An Ecstasy Precursor Seized in Sydney, Australia | 10.1111/j.1556-4029.2007.00480.x


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## William Dampier

This synthesis of glycidat works, but for hydrolysis would better use hydrochloric acid. And bromopropionate can replace to chloropropionate.


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## kawaii

does this synthesis Works for pmk ethyl glycidate cas28578-16-7? It's much more complicated than pmk methyl glycidate


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## William Dampier

kawaii said:


> does this synthesis Works for pmk ethyl glycidate cas28578-16-7? It's much more complicated than pmk methyl glycidate



kawaiiStep 2 there is a route for this CAS. But I would use softer conditions when reactions with alkali (1eq of NaOH and low temp), if there is access to aqueous hydrochloric acid.


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## Montecristo

Alternatives for ether?


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## William Dampier

thatfella said:


> Alternatives for ether?



thatfellaMethyl, ethyl, tert-butyl, isopropyl, etc ethers


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## Montecristo

William Dampier said:


> Methyl, ethyl, tert-butyl, isopropyl, etc ethers



William DampierWould Step 2 be good for converting the new PMK ethyl glycidate? Seems it needs saponification with sodium first, would this tek cover that with the NaOH reflux? 
By 90% aqueous alcohol you mean 90% abv? not 90% aqueous?


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## btcboss2022

William Dampier said:


> *Step 1. PMK-glycidate.
> View attachment 1477*
> 1. Freshly prepared powdered sodium ethoxide (23 g.) was added during 4 hours to a stirred mixture of piperonal (50 g.) and ethyl a-bromopropionate (61 g.), cooled in ice-salt.
> 2. Stirring was continued overnight at room temperature and for 6 hours on the water-bath; ice-water was then added, and the mixture acidified with dilute acetic acid.
> 3. The glycide ester was extracted with ether, and ethereal solution washed with aqueous sodium carbonate and dried with sodium sulphate.
> 4. After removal of ether, the residue was distilled and collected between 70 *C and 200* at 20 mm.
> 5. Subsequent redistillation gave B-3,4-methylenedioxyphenyl-a-methylglycide ester (40 g.) b.p. 184-186*/14 mm (yield, 48%).
> 
> 
> *Step 2. 3,4-methylendioxyphenylacetone.
> View attachment 1478*
> 1. The ester (35 g.) was refluxed for 5 hours with a solution of sodium hydroxide (10 g.) in 90% aqueous alcohol (150 ml).
> 2. After removal of part of the alcohol by distillation, the residue was diluted with a large volume of water and extracted with ether, and with the addition of a trace of copper powder;
> 3. The liquid was then distilled slowly under reduced pressure in the presence of copper powder. Redistillation of the product gave 3,4-methylenedioxybenzylmethylketone (11,1 g.) b.p 154-156/11 mm. (yield, 44.5%).



William DampierCould be copper replaced by any other metal? Iron, Aluminum...?
Thanks.


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## William Dampier

btcboss2022 said:


> Could be copper replaced by any other metal? Iron, Aluminum...?
> Thanks.



btcboss2022No. But you can use another route, with alkali and hydrochloric acid.


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## btcboss2022

William Dampier said:


> No. But you can use another route, with alkali and hydrochloric acid.



William DampierLink please?


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## William Dampier

btcboss2022 said:


> Link please?



btcboss2022It depends on what starting reagents you have. Do you have a piperonal?


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## btcboss2022

William Dampier said:


> It depends on what starting reagents you have. Do you have a piperonal?



William DampierI have PMK oil


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## btcboss2022

btcboss2022 said:


> I have PMK oil



btcboss2022Sorry ;-) Not final product new cas pmk oil to process 28578


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## btcboss2022

btcboss2022 said:


> Sorry ;-) Not final product new cas pmk oil to process 28578



btcboss2022I can obtain the same cas in powder


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## William Dampier

btcboss2022 said:


> I can obtain the same cas in powder



btcboss2022if it is a powder - for rearrangement needs only HCl acid and water (better that NaOH aq. soln only). If the liquid - needs NaOH and HCl desirable


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## William Dampier

btcboss2022 said:


> Could be copper replaced by any other metal? Iron, Aluminum...?
> Thanks.



btcboss2022


William Dampier said:


> No. But you can use another route, with alkali and hydrochloric acid.


In general, you can do without metal, it is here more in the role of a catalyst.


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## chriswaters

@William Dampier





William Dampier said:


> if it is a powder - for rearrangement needs only HCl acid and water (better that NaOH aq. soln only). If the liquid - needs NaOH and HCl desirable



William Dampier
So if reacting the powder "pmk ethyl glycidate" with HCL and water, it will convert to PMK or PMK glycidic acid?


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## Fring

@William Dampier , the second part would be only applicable for the non ethyl pmk that we have now , right?


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## William Dampier

For any glycide ether, everything should be the same. Methyl, ethyl, propyl, tert-butyl, etc - the same


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## Fring

William Dampier said:


> For any glycide ether, everything should be the same. Methyl, ethyl, propyl, tert-butyl, etc - the same



William Dampierthtas what i thought ... and in fact this is real, the problem is due to we were doing the olg GLY conversion and with this new, when we see a tottally differerent result we all thinks there's something wrong, and the key its just vacuum distillation..it losses a small part of water and gives the Ketone... different colour, very dark red or brown


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## William Dampier

The chemical structure of any ester of glycidate consists of the same acid and alcohol. What alcohol was for etherification - such an acid ester. Saponification of ethers with alkali - in all cases, the same.

The typical Darzen reaction uses the ethyl version of the ether.


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## summer_child

Ethyl a-bromopropionate might present a challenge to get or make. One could replace it with ethyl propionate and perform an epoxidation with performic acid.View attachment 5322View attachment 5323


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## William Dampier

summer_child said:


> Ethyl a-bromopropionate might present a challenge to get or make



summer_childWell available in China


summer_child said:


> . One could replace it with ethyl propionate and perform an epoxidation with performic acid.


Yes, you are now talking about another interesting route. Alpha-methylcinnamic acid is also available in China.


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## summer_child

William Dampier said:


> Well available in China



William DampierTrue , but I always like to think of synthesis pathways that can be completed by going to the local hardware store even if they are less efficient.
Edit: I noticed the picture is my other posts don't show up so I added them here


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