[pharmacydoctor]

The reactio is   HOOC?R?COOH   ?  MeLi   ?  CH3OC?R?COCH3
    I have done it many times, but can not obtain the product. From TLC, the double carboxylic acid  has not reaction. I use anhydrous THF as solvent, sirt 2h under N2 and ice bath.  Use NH4Cl quench the reaction.
    I don't konw why I cann't obtain the product? Please give me some advises, thank!

   Other question: Why the double carboxylic acid rf=0.5 run TLC in PE(petro ether)?

[movies]

The MeLi will just deprotonate your carboxylic acids making a carboxylate anion which is practically impossible to add into with another MeLi.

[pharmacydoctor]

But from other references , using 2eq MeLi can transit carboxylic acid to ketone! I don't know why I can't?

[Mitch]

Can you cite the literature you're working from?

[pharmacydoctor]

I cite the paper is J.O.C   1986,51, 5348-5353
compound 18

[russellm72]

Hi,

I have done this reaction before from benzoic acid to acetophenone using 2 eq

[russellm72]

Sorry I said 2 eq MeLi and TMSCl.

See Rubottom and Kim, J. Org. Chem., 1983, 48, 1550-1552.

R.

[pharmacydoctor]

Dear: russellm72

Could you tell your reation's process more detail or your paper?
I know the paper :Rubottom and Kim, J. Org. Chem., 1983, 48, 1550-1552
I think my reaction have different with above paper. I want transit double carboxylic acid  to double ketone! The double carboxylic acid is very easy to make H-bond!

[russellm72]

Ok.

I did 4-ClPhCO2H to 4-ClPhC(O)CH3 using the paper i mentioned.

The chlorobenzoic acid (0.48 mmol) was dissolved in THF (4ml) and cooled to 0oC. Added MeLi (1.6M in Et2O, 4 eq) and stirred at 0oC for 90 mins. Quenched with TMSCl (1.2 ml, 9.5 mmol) and allowed to warm to rt. After 30 mins added 1N HCl (4ml) and stirred 30 mins. Extracted into ether, dried MgSO4, filtered, concentrated and purified by HPLC. Yield 64%.

Note. We just use Aldich sure seal bottles of THF as all this drying over sodium is a safety concern on a site. It's Ok at University.

R.

[pharmacydoctor]

Thank you very much!
THF have been distilled with benzophenone and N2. Stirred 3h rt, the product  still not appear.
Could I use NH4Cl replace Me3SiCl to quench the reaction?
In some references, describe over 2eq MeLi would lead to side reaction. In your experiment, use 4eq
MeLi can obtain product and have no by product?

[russellm72]

No I think it's important you use TMSCl, check the reference I gave you.

I must of used 4eq as the paper suggested this. I did the reaction with a [U-14C] ring and by TLC the reaction had gone 80% but after columing and not bothering with side fractions I isolated 64% yield which was Ok.

Clearly it is substrate dependant but I think you should try with TMSCl. Your THF sounds fine to me. Like I said while I was at Uni we used to go to all the trouble of distilling and keeping under N2 but now I just use Aldrich stuff (sureseal) under a N2 baloon.

Are you sure your MeLi is any use?

R.

[pharmacydoctor]

 What is the mechanism of use TMSCL to quench the reaction? I doubt my substrate cann't do this reaction. I have repeated it many times. Little product could be detected. From the describe of you,I think this reaction is not absolute anhydrous and anoxygenous.