P2P synthesis from BMK Glycidic Acid (sodium salt) - modified version

[G.Patton]

Distillation adapter

Hello, do you mean Claisen adapter?

Pour 100 - 150 ml of Phosphoric acid

What concentration of the acid have you used? Why have you added so much acid? 100 - 150 ml is 3.5 - 5.2 fold excess.

Why don't you added the acid into glycidate aqueous solution and did in vice versa? I guess, It takes a lot of time.

 

[Heisenblack]

Hello, do you mean Claisen adapter?


What concentration of the acid have you used? Why have you added so much acid? 100 - 150 ml is 3.5 - 5.2 fold excess.

Why don't you added the acid into glycidate aqueous solution and did in vice versa? I guess, It takes a lot of time.

G.PattonYes Claisen adapter.

I used 100 ml for 50 gr batch, excess acid is to prevent the formation of layers in the flask and to make the reaction go on immediately, this minimizes the formation of byproducts. The amount of acid can still be optimized to make it economical. When I had less acid, I could see the brown glycidate layer in the flask. I forgot to mention the pH of p2p in the receiving flask was 5.5 - 6.

The process takes about 1 hour to complete.

 

[G.Patton]

it does not change the reaction path, but the rate of the reaction

w2x3f5I ask because hardly imagine large scale of dripping the reaction solution to acid. It would take a lot of time. I guess, you have to use couple drip funnels or something different.

 

[w2x3f5]

I ask because hardly imagine large scale of dripping the reaction solution to acid. It would take a lot of time. I guess, you have to use couple drip funnels or something different.

G.PattonIf the scale is large, then there is no problem to drip with a peristaltic pump (or any other suitable pump), all depending on the heating power and the heat capacity of the acid.

 

[K-Cyanide]

@w2x3f5 fyi the operator of the said synthesis has a lot of experience in organic synthesis. Below the answers to your questions:

• No there were no precipitates during the hydrolysis.
• Amount of acid, the lower value of the described method was taken.
• A ratio of 1:10, where 1 is the expected product and 10 the amount of distillate (water and product) is quite common as a rule of thumb.
• 110 C in the reactor of course
• No, you cannt use boiling stones in a glass reactor. The stirrer is a PTFE 4 blade stirrer which mixes the reaction mass vigorously, so there should be no need for boiling stones. But maybe this method needs a calm boiling with bubbles, like the Leuckart-Wallach reduction.
• Scary to start with 500g. No, first you cannot run very small runs in a glass reactor due to the gap of the stirrer to the glass at the bottom, and secondly there are no reagents used which are a concern.
• Yes. the yield is lousy, but honest. 300ml were expected, at least.

Thank you for your effort.

 

[w2x3f5]

@w2x3f5 fyi the operator of the said synthesis has a lot of experience in organic synthesis. Below the answers to your questions:

• No there were no precipitates during the hydrolysis.
• Amount of acid, the lower value of the described method was taken.
• A ratio of 1:10, where 1 is the expected product and 10 the amount of distillate (water and product) is quite common as a rule of thumb.
• 110 C in the reactor of course
• No, you cannt use boiling stones in a glass reactor. The stirrer is a PTFE 4 blade stirrer which mixes the reaction mass vigorously, so there should be no need for boiling stones. But maybe this method needs a calm boiling with bubbles, like the Leuckart-Wallach reduction.
• Scary to start with 500g. No, first you cannot run very small runs in a glass reactor due to the gap of the stirrer to the glass at the bottom, and secondly there are no reagents used which are a concern.
• Yes. the yield is lousy, but honest. 300ml were expected, at least.

Thank you for your effort.

K-Cyanideyou need to figure out what were the differences in the experiments, in addition, you did it in a reactor, and initially the experiment was done in a flask. While it strikes me that you have mechanical mixing, there was no mixing in the initial experience and porous stones were used accordingly (by the way, during hydrolysis of free glycidate in pure phosphoric acid, carbon dioxide bubbles form only on the surface of the stones, I emphasize the synthesis was without water, only that water that was present in phosphoric acid)

 

[btcboss2022]

Introduction

This is the modified preparation of P2P CAS 103-79-7 made using BMK Glycidic Acid ( sodium salt ) CAS 5449-12-7 with Phosphoric Acid 85% CAS 7664-38-2

Equipment and glassware:

• 1000 ml 3-neck Round bottom flask
• Distillation adapter
• Condenser with a receiving flask
• Dropping funnel
• Thermometer to control liquid temperature
• Hot plate or Magnetic stirrer (do not place the flask
• Boiling stones (pieces of broken porous ceramics)

Set-up:

Use a 3-neck Round bottom flask - on one neck you put the thermometer to measure the temperature of the liquid; on the second neck you put the distillation adapter with a condenser connected to the receiving flask, and on the third neck you put the dropping funnel.

Instruction:

For 50 gr batch

1. Pour 100 - 150 ml of Phosphoric acid into the flask, add boiling stones (3 - 4 pea size porous ceramic) and heat to 110 °C
2. Dissolve the BMK sodium salt in boiling water (optimally 12 ml of water per 1 g of BMK sodium salt) and add to the dropping funnel
3. Slowly add the dissolved solution into the acid drop by drop

The reaction will begin immediately, and you will distil pure p2p into the receiving flask. The distillate will be milky water (similar to steam distillation). The reaction is complete once your distillate becomes clear water. The p2p should be extracted using 3 x 30 ml DCM (any other solvent will probably work), drying over molecular sieves/silica gel and evaporating the solvent.

When done correctly, the yield will be 80%+.

Important notes:

• Do not place the flask directly on the hotplate, use tripod stand
• Boiling stones are very important if you do not use a stirrer
• The addition of dissolved glycidic acid should be slow (drop by drop using dropping funnel) for good yield - be patient
• The temperature should be maintained at 110 °C, not higher

I have done this reaction using 20 gr BMK sodium salt - yield 12 ml (88%) and 50 gr - yield 28 ml (83.5%).

The method was done under the instruction and guidance of @w2x3f5 , all credit goes to him.

HeisenblackHello,

I tested this method in small scale 50gr BMK CAS 5449, 100ml of Phosphoric Acid 85% and 600ml of water and here is my result:

The method works properly I don't know the exactly yield yet but only seeing the oil layer I can say that will be a good yield.

The P2P is totally clean like after steam distillation(in fact is what you are doing practically).

Talking about timing could take more or less the same time as the standard hydrolysis( I did it dripping) with the advantage that you get the pure product directly.

An advice to save some time is to begin adding a bigger portion of the bmk solution and wait it gets hot instead to begin only with drops the reason is that condensation wont starts until a significant mass of water is being evaporated, glass get hot....you know, so starting with drops will take more time than adding a bigger part once condensation begins you can start adding the solution again in drops.(totally optional)

I have seen the pics uploaded of that process :

http://bbzzzsvqcrqtki6umym6itiixfhni37ybtt7mkbjyxn2pgllzxf2qgyd.onion/attachments/1uj6edpzrl-jpg.12849/

http://bbzzzsvqcrqtki6umym6itiixfhni37ybtt7mkbjyxn2pgllzxf2qgyd.onion/attachments/bshoqvbxqv-jpg.12850/

I think that something don't match on them(are not critics only curiosity):

- P2P has more density than water so it should be the bottom layer not the top layer, the reasons could be:
1. In the moment of the pics the mixture has a high temp.
2. The mixture is acid(or alkali but in that case with the reagents used is totally impossible), and this case would be strange because at 110C you only should be evaporating water with P2P the mixture wouldn't be acid

- The color of the oil layer is more brown than yellow, is more similar to the color after normal hydrolysis.

I uploaded a pic of a part of my final mixture of that method to see better what I mean

I'm happy with the result so I will try it in big scale asap.
Thanks.

 

[w2x3f5]

Hello,

I tested this method in small scale 50gr BMK CAS 5449, 100ml of Phosphoric Acid 85% and 600ml of water and here is my result:

The method works properly I don't know the exactly yield yet but only seeing the oil layer I can say that will be a good yield.

The P2P is totally clean like after steam distillation(in fact is what you are doing practically).

Talking about timing could take more or less the same time as the standard hydrolysis( I did it dripping) with the advantage that you get the pure product directly.

An advice to save some time is to begin adding a bigger portion of the bmk solution and wait it gets hot instead to begin only with drops the reason is that condensation wont starts until a significant mass of water is being evaporated, glass get hot....you know, so starting with drops will take more time than adding a bigger part once condensation begins you can start adding the solution again in drops.(totally optional)

I have seen the pics uploaded of that process :

http://bbzzzsvqcrqtki6umym6itiixfhni37ybtt7mkbjyxn2pgllzxf2qgyd.onion/attachments/1uj6edpzrl-jpg.12849/

http://bbzzzsvqcrqtki6umym6itiixfhni37ybtt7mkbjyxn2pgllzxf2qgyd.onion/attachments/bshoqvbxqv-jpg.12850/

I think that something don't match on them(are not critics only curiosity):

- P2P has more density than water so it should be the bottom layer not the top layer, the reasons could be:
1. In the moment of the pics the mixture has a high temp.
2. The mixture is acid(or alkali but in that case with the reagents used is totally impossible), and this case would be strange because at 110C you only should be evaporating water with P2P the mixture wouldn't be acid

- The color of the oil layer is more brown than yellow, is more similar to the color after normal hydrolysis.

I uploaded a pic of a part of my final mixture of that method to see better what I mean
View attachment 14075

I'm happy with the result so I will try it in big scale asap.
Thanks.

btcboss2022wait your yield
possibly different purity of glycidate

 

[btcboss2022]

wait your yield
possibly different purity of glycidate

w2x3f530ml of P2P without extracting and drying yet.

 

[btcboss2022]

30ml of P2P without extracting and drying yet.

btcboss2022My final result after extracting and drying are 31ml of pure P2P

 

[w2x3f5]

My final result after extracting and drying are 31ml of pure P2P

btcboss2022You used about 0.25 moles of glycidate and got about 0.23 moles of p2n, a yield of 92.5-93 percent of theory. My congratulations and thanks for testing my version of hydrolysis and confirming a good yield of the substance.

 

[crocodile]

Would it be possible to just add the bmk powder and water at the beginning of the synthesis and just increasing the heat slowly slowly until it starts boiling instead of adding it drop by drop?
Also, if that would work will a large stainless steel distiller would work for this method?

 

[crocodile]

Would it be possible to just add the bmk powder and water at the beginning of the synthesis and just increasing the heat slowly slowly until it starts boiling instead of adding it drop by drop?
Also, if that would work will a large stainless steel distiller would work for this method?

crocodileOr maybe use a 100L glass reaction vessel with a periliastic pump that way 400 kilo batches can be processed quite easily.

 

[w2x3f5]

Would it be possible to just add the bmk powder and water at the beginning of the synthesis and just increasing the heat slowly slowly until it starts boiling instead of adding it drop by drop?
Also, if that would work will a large stainless steel distiller would work for this method?

crocodileWhen I wrote this synthesis, my main idea was to quickly distill off the formed phenylacetone from the reaction mass, to reduce the formation of impurities and increase the yield of the substance

 

[btcboss2022]

FYI
I received a sample of BMK powder CAS 5413-05-8 and I decided to test it with that method too just about curiosity without thinking and any chemical factor(normally I will hydrolize it with HCL).
The first "problem" is that when you solve the powder in boiling water the powder is automatically converted in oil with similar color and density as P2P.
So if you add the mixture with an addition funnel or similar the fist thing to be added will be this oil not water due this oil is in the top layer.
When I finished all the process, goes like the other one, I obtained an oil that I thought it was logically P2P but don't smells like P2P so I'm practically sure that is all the unreacted 5413 oil+possibly some P2P(but if it is there is in very low %)
In short this method at least with that conditions don't works for CAS 5413-05-8, I will extract it all and hydrolyze it with HCL and update you with the difference.
I will hydrolize it with HCL because 5413 has the same appearance and above all the same identical smell to the old 16648(MAPA).
If finally it don't properly too I will use the alkali reflux and later the acid reflux but I guess it will works perfectly with the HCL hydrolysis.

 

[w2x3f5]

FYI
I received a sample of BMK powder CAS 5413-05-8 and I decided to test it with that method too just about curiosity without thinking and any chemical factor(normally I will hydrolize it with HCL).
The first "problem" is that when you solve the powder in boiling water the powder is automatically converted in oil with similar color and density as P2P.
So if you add the mixture with an addition funnel or similar the fist thing to be added will be this oil not water due this oil is in the top layer.
When I finished all the process, goes like the other one, I obtained an oil that I thought it was logically P2P but don't smells like P2P so I'm practically sure that is all the unreacted 5413 oil+possibly some P2P(but if it is there is in very low %)
In short this method at least with that conditions don't works for CAS 5413-05-8, I will extract it all and hydrolyze it with HCL and update you with the difference.
I will hydrolize it with HCL because 5413 has the same appearance and above all the same identical smell to the old 16648(MAPA).
If finally it don't properly too I will use the alkali reflux and later the acid reflux but I guess it will works perfectly with the HCL hydrolysis.

btcboss2022acetoacetates are hydrolyzed in the cold in sulfuric acid, if I'm not mistaken, I can find a method if you need

 

[btcboss2022]

acetoacetates are hydrolyzed in the cold in sulfuric acid, if I'm not mistaken, I can find a method if you need

w2x3f5Dont worry I have all the information needed just trying your method with other bmk cas thanks anyway

 

[crocodile]

FYI
I received a sample of BMK powder CAS 5413-05-8 and I decided to test it with that method too just about curiosity without thinking and any chemical factor(normally I will hydrolize it with HCL).
The first "problem" is that when you solve the powder in boiling water the powder is automatically converted in oil with similar color and density as P2P.
So if you add the mixture with an addition funnel or similar the fist thing to be added will be this oil not water due this oil is in the top layer.
When I finished all the process, goes like the other one, I obtained an oil that I thought it was logically P2P but don't smells like P2P so I'm practically sure that is all the unreacted 5413 oil+possibly some P2P(but if it is there is in very low %)
In short this method at least with that conditions don't works for CAS 5413-05-8, I will extract it all and hydrolyze it with HCL and update you with the difference.
I will hydrolize it with HCL because 5413 has the same appearance and above all the same identical smell to the old 16648(MAPA).
If finally it don't properly too I will use the alkali reflux and later the acid reflux but I guess it will works perfectly with the HCL hydrolysis.

btcboss2022So just to be clear, you are saying this method works for 5449 but not for 5413 or that it doesn't work for either?

 

[btcboss2022]

So just to be clear, you are saying this method works for 5449 but not for 5413 or that it doesn't work for either?

crocodileFor 5449 works for 5413 dont works.

 

[crocodile]

For 5449 works for 5413 dont works.

btcboss2022Ah, very interesting and annoying.

 

[btcboss2022]

I will try a faster method, I will do the process in the rotavap in vacuum and I will update you.
The idea is distill faster with less heating, the water mixer could be added in portions anyway throw the vacuum pipe ;-)
I will setup it at 57-58C with 20 kPa of vacuum.
But should be faster for big scale for sure.

 

[w2x3f5]

I will try a faster method, I will do the process in the rotavap in vacuum and I will update you.
The idea is distill faster with less heating, the water mixer could be added in portions anyway throw the vacuum pipe ;-)
I will setup it at 57-58C with 20 kPa of vacuum.
But should be faster for big scale for sure.

btcboss2022I have a feeling that the solubility of the ketone in water vapor will drop
As an option, supply steam from a generator and additionally heat it (superheated steam), this version will definitely work much better