[kriggy]

Hey guys I run into a bit of a dead end at the moment.
Im trying to perform Grignard type reaction to convert a methylester into tertiary alcohol.  I used excess of PhMgCl which yielded the product (about 70% via HPLC) but it cannot be separated by column because of lots of different impurities that co-elute with it. Similar problem is with iPrMgCl.LiCl complex which was more reactive but I still get tons of different compounds. My starting material has pyridine part as well which I thought could react with the grignard (Chichibabin like reaction) but after looking up into my textbook it seems that those reactions require harsher conditions.

My conditions were: dissolve in dry THF, cool in ice bath and then add grignard and stir untill done at room temp, 30mins for isopropyl and 48hrs for phenyl.

Im thinking about using organolithium reagents but I think  they are more reactive than grignards which may cause more side reactions? Or making organozinc reagent in situ (wouldnt the pyridine ring interfere with alkyl halide?). I cannot heat the reaction because the starting material is chiral and would racemize (I could do that and separate the enantiomers later but I dont want to devise a new resolution process unless I have to.)

Im gonna try some R-Li nucleophile tommorow but Im just looking for thoughts or ideas from more experiences chemists.

Thank you

[wildfyr]

not to be a dick but why not just dissolve this material in dry tertbutanol and catalytic sulfuric acid?

[OrganicDan96]

lower temperature? -78°C?

[kriggy]

not to be a dick but why not just dissolve this material in dry tertbutanol and catalytic sulfuric acid?

eee

I think my description was not clear enough..
Im trying to do this
R-COOMe -> RR´R´COH kinda like converting methyl benzoate into triphenylmethanol

not
R-COOMe -> RCOOtBu

lower temperature? -78°C?

damn, didnt occur to me. Seems quite obvious

thanks

[rolnor]

If you get 70%, is this not more a separationproblem? You can add some triethylamine to the mobile-phase when you run TLC if the pyridine gives tailing, if you run flash-chromatography you can then try to crystalize.

[wildfyr]

Oops, of course. My reply was ignorant. I misread.

[rolnor]

Also when you have a basic pyridine in the molecule you can purify in the workup by extracting it to water phase with acid and back to organic phase with a little ammonia.

[kriggy]

If you get 70%, is this not more a separationproblem? You can add some triethylamine to the mobile-phase when you run TLC if the pyridine gives tailing, if you run flash-chromatography you can then try to crystalize.

I think so. The HPLC and TLC looked like a huge mess, it was maybe not even 70%. Anyway, after column I got two impurities and something that was supposed to have be my product. HPLC of it looked quite terrible but for some reason NMR is rather good, showing tons of small impurity peaks but that is nothing that cant be solved by crystalization.

Oops, of course. My reply was ignorant. I misread.

np mate

Also when you have a basic pyridine in the molecule you can purify in the workup by extracting it to water phase with acid and back to organic phase with a little ammonia.

Guess I could try this as well but Im thinking that most of the impurities are containing the pyridine ring as well. But worth trying when I repeat the reaction again.


btw, the reaction with turbo-Grignard (iPrMgCl.LiCl) was hillariously fast (about 30min at -78°C with no excess of the Grignard) compared to huge excess of PhMgCl at RT. There might be some steric reasons but since I dont have the LiCl complex with PhMgCl available at the moment... Can it be just made by adding some LiCl into the reaction or does it require some more specific conditions?