[linh_ngt]

Dear all members, I have an reaction that make me feel confused and hope that s/o can help me
I have cpd methyl acetoacetate and wanna protect its ketone group. I used ethylene glycol, pTsA and toluene for this reaction. Here is the procedure: I put starting materials, ethylene glycol in toluene, add pTsA (p-toluenesulfonic acid). The reaction medium was equipped with a Dean-Stark apparatus and then refluxed until no more water was collected (abt 8hrs). Then, I use the vacuum machine for separate the products based on their boiling points ( toluene first, starting material or products after that). At last, i check on TLC and make 1H-NMR but I did not obtain my desire products?
Is there anyone that can help me for this prob?
THank you all so muchhhhhhhhh!

[discodermolide]

Dear all members, I have an reaction that make me feel confused and hope that s/o can help me
I have cpd methyl acetoacetate and wanna protect its ketone group. I used ethylene glycol, pTsA and toluene for this reaction. Here is the procedure: I put starting materials, ethylene glycol in toluene, add pTsA (p-toluenesulfonic acid). The reaction medium was equipped with a Dean-Stark apparatus and then refluxed until no more water was collected (abt 8hrs). Then, I use the vacuum machine for separate the products based on their boiling points ( toluene first, starting material or products after that). At last, i check on TLC and make 1H-NMR but I did not obtain my desire products?
Is there anyone that can help me for this prob?
THank you all so muchhhhhhhhh!

How much water did you collect? Did it correspond to the theoretical value you expected?
If you did not get the product what did you get?
The ketone in your starting material is easily enolised, perhaps that's all you did? Hence no reaction

[Dan]

Transesterification with ethylene glycol is also possible as a side reaction, and has been previously reported for this substrate:

T. Boisse et al. Tetrahedron, 2007, 63, 10511–10520

In this paper they reverse this unwanted side reaction by taking the crude acetal and treating it with MeONa/MeOH to regenerate the methyl ester.

This may or may not be the issue with your reaction, we need to know what was in your crude reaction mixture to diagnose the problem. What molar excess of the diol are you using?

The best conditions in the lit appear to be pTSA/ethylene glycol/trimethyl orthoformate at room temp (98% yield):

M. Sutter Tetrahedron Letters, 1989, 30, 5417-5420

I'd try that instead. An hour in the library can save a day in the lab...

[linh_ngt]

Dear all members, I have an reaction that make me feel confused and hope that s/o can help me
I have cpd methyl acetoacetate and wanna protect its ketone group. I used ethylene glycol, pTsA and toluene for this reaction. Here is the procedure: I put starting materials, ethylene glycol in toluene, add pTsA (p-toluenesulfonic acid). The reaction medium was equipped with a Dean-Stark apparatus and then refluxed until no more water was collected (abt 8hrs). Then, I use the vacuum machine for separate the products based on their boiling points ( toluene first, starting material or products after that). At last, i check on TLC and make 1H-NMR but I did not obtain my desire products?
Is there anyone that can help me for this prob?
THank you all so muchhhhhhhhh!

How much water did you collect? Did it correspond to the theoretical value you expected?
If you did not get the product what did you get?
The ketone in your starting material is easily enolised, perhaps that's all you did? Hence no reaction

Yep, the amount of water is over than the theoretical value ( i think that's prob of the solvent (may be it has not dried absolutely yet) but it will not affect too much). Actually, the starting material has the origin from Aldrich, agree with u that it was enolised (cause i see the uv spot when checking TLC under the UV light)) but this will be the equilibrium,  then of course i still have my stable starting material, right??? And also, on the 1H-NMR, i still see some peaks of my desire product, but not totally sure ( I think it has contamminat of starting material. I also try to separate by TLC but i cant find out the available solvent mixture. There's only 1 spot on the TL (
I find on internet, read some papers; recognize that they can do this reaction easily, so what i did st wrong?

[linh_ngt]

Transesterification with ethylene glycol is also possible as a side reaction, and has been previously reported for this substrate:

T. Boisse et al. Tetrahedron, 2007, 63, 10511–10520

In this paper they reverse this unwanted side reaction by taking the crude acetal and treating it with MeONa/MeOH to regenerate the methyl ester.

This may or may not be the issue with your reaction, we need to know what was in your crude reaction mixture to diagnose the problem. What molar excess of the diol are you using?

The best conditions in the lit appear to be pTSA/ethylene glycol/trimethyl orthoformate at room temp (98% yield):

M. Sutter Tetrahedron Letters, 1989, 30, 5417-5420

I'd try that instead. An hour in the library can save a day in the lab...

Thank u for your references! aCTUALLY, i think procedure of the 1st ref's quite complicated and takes a long time for treatment. I wanna try the reaction like the 2nd way but no chemicals of trimethyl orthoformate. Maybe it's not popular in my lab

[Dan]

on the 1H-NMR, i still see some peaks of my desire product, but not totally sure ( I think it has contamminat of starting material. I also try to separate by TLC but i cant find out the available solvent mixture. There's only 1 spot on the TL (

That sounds like it might be the transesterified product, which probably looks a bit like a mixture of the desired product and ethylene glycol in NMR, but is one spot by TLC... If you post the NMR we can have a look.

Trimethyl orthoformate is very cheap, just buy some. Check to see if you have any other orthoesters as they will probably work as well, e.g. trimethyl orthoacetate.

[linh_ngt]

on the 1H-NMR, i still see some peaks of my desire product, but not totally sure ( I think it has contamminat of starting material. I also try to separate by TLC but i cant find out the available solvent mixture. There's only 1 spot on the TL (

That sounds like it might be the transesterified product, which probably looks a bit like a mixture of the desired product and ethylene glycol in NMR, but is one spot by TLC... If you post the NMR we can have a look.

Trimethyl orthoformate is very cheap, just buy some. Check to see if you have any other orthoesters as they will probably work as well, e.g. trimethyl orthoacetate.

That seems to be reasonable. May be u r right. The 1H-NMR looks like a mixture of the desire product and ethylene glycol
So in this case, i think i'll try to back-transesterfication by treating with MeOH/MeONa. Is that ok?

[Dan]

I don't know. Methoxide will work if transesterification with ethylene glycol is the problem - I've already told you we need to know what is in the crude reaction mixture to diagnose the problem, and as it stands you have provided very little information.

Unless you can provide some data, NMR, MS etc. we can only conjecture as to what could plausibly have gone wrong. Your vague description of the 1H NMR spectrum is not enough evidence to suggest the next experiment.

If you post data I'm happy to look at it and offer my opinion.

[linh_ngt]

I don't know. Methoxide will work if transesterification with ethylene glycol is the problem - I've already told you we need to know what is in the crude reaction mixture to diagnose the problem, and as it stands you have provided very little information.

Unless you can provide some data, NMR, MS etc. we can only conjecture as to what could plausibly have gone wrong. Your vague description of the 1H NMR spectrum is not enough evidence to suggest the next experiment.

If you post data I'm happy to look at it and offer my opinion.

Here I show u 2 pics of 1H-NMR spectra. I did this reaction 2 times. I think in the 1st pic, i see the signals of ethylene glycol and as u said, it's also the peaks of the side product (tranesterfication), right.
On the 2nd pic (when i did again), i also see some peaks of my desire product, like methoxy (CH3-O), methylen (s, CH2-O) but for the 4H of ethylene glycol ( it should be the signal of multiplet, right) i cant observe.
Thank u if u can give me some comments abt these spectra

[james_a]

Rule #1 if you are trying to synthesize a known compound is to track down its NMR spectrum and references to its synthesis. Then will you have a much firmer idea of what you are supposed to be looking for.

Why did you choose to start with the methyl ester? I don't have Scifinder, but can't find many references to the compound you wish to synthesize. On the other hand the ethyl ester is widely available.
http://www.lookchem.com/cas-641/6413-10-1.html

The lack of references to the methyl ester is puzzling - for instance on ChemSpider a search for  Methyl 2-methyl-1,3-dioxolane-2-acetate yields no results. One could surmise that the lack of references is due to the difficulty of synthesis through the method you are pursuing.

If you really want to make this compound I would start with the ethyl ester and make the dioxolane using a known literature procedure, and then transesterify using LiOCH3.

[buRnINGbeND]

maybe try PPTS?  it might be a little less harsh of an acid for you.

[linh_ngt]

I have good news for my reaction.
I just change the solvent from toluene into chloroform and i obtained my desire product, yeah yeah \m/
I really dont understand too much abt the effect of solvent to the reactions. Is there anyone having any references abt this?
Thank your for your all contributions. I'm really happy when finding out this website

[Dan]

That's interesting, thanks for updating. Can you post your conditions?

[linh_ngt]

Ah, ethylene glycol, pTsA and chloroform as solvent
I use CHCl3 because i have the reaction system that is quite different from the Dean-stark apparatus.
I just try and think it'll not be effective but it really runs well

[Dan]

Ah, ethylene glycol, pTsA and chloroform as solvent
I use CHCl3 because i have the reaction system that is quite different from the Dean-stark apparatus.
I just try and think it'll not be effective but it really runs well

Can you give molar equivalents of the reagents please? Did you use a drying agent of any kind?