DIBAL Reduction of Ester to Alcohol
(E)-Ethyl 3-(2-chlorophenyl)acrylate (1.5 g, 0.007 mol) was dissolved in 15 mL of anhydrous dichloromethane, cooled to -78 oC and treated with a solution of di-iso-butylaluminum hydride (1.0 M solution in hexane, 21.4 mL, 0.021 mol) over a period of 20 minutes (the solution turned yellow in color). After 1.5 hours total at -78 oC, the reaction was quenched with methanol (15 mL) at -78 oC (the solution became colorless and then a white solid precipitated out), warmed to 23 oC (over 9 hrs) and treated with a saturated aqueous solution of NH4Cl (60 mL). The resulting mixture was extracted with dichloromethane (2 × 100 mL) (emulsion formed was filtered over Celite to remove white gummy precipitate). The combined extracts were dried (Na2SO4) and concentrated under vacuum to give (E)-3-(2-chlorophenyl)prop-2-en-1-ol which was purified by column chromatography (silica gel, 0-50% ethyl acetate in hexanes) as a pale brown oil (0.45 g, 37% yield, NMR complies). 0.8 g of starting ester was also recovered. Ref: WO2005/097744
Any suggestion how to improve the yield?
pmgb
September 13, 2008 at 12:23 am
You might try a 10% solution of Rochelle salt instead of the ammonium chloride. It has helped in our case and you usually don’t get the gummy precipitate you described. Also, we have had increased yields when we were using Dibal in toluene and running the reaction in the same solvent. Hope this helps.
shirow
September 13, 2008 at 12:36 am
Thank you very much.
pmgb
September 13, 2008 at 1:56 am
If you’re still recovering ester at the end, you probably need to just add more DIBAL. Either that, or your DIBAL is no good.
Could also be that you need to let the reaction run longer.
Gus Musselmann
September 13, 2008 at 2:10 am
Thanks. DIBAL was taken from a new bottle. What would happen if I warm the reaction to 0 oC before quenching with methanol. Will the double bonds get reduced?
pmgb
September 13, 2008 at 8:38 pm
I can’t think offhand of any time where I ran a DIBAL at any temp other than -78. Doesn’t mean its’ not worth a try, though.
Either way, you should probably at least try to see if you can’t consume all your SM by adding more reagent.
Another thing to try that I’m fond of is Red-Al (a/k/a Vitride)
DIBAL certainly can reduce conjugated double bonds, but it’s not always a problem.
Gus Musselmann
September 13, 2008 at 8:51 pm
Thanks.
pmgb
September 13, 2008 at 11:37 pm
The conjugate C=C bond reduction is a competing reaction, not over-reduction (it goes through enolate). There is no reason why not doing it at -78 to RT. Since your cinnamoc alcohol is not very sensitive to acid I would work up the react mix with 1M sulfuric acid (the suggested tartarate is also a good alternative). Or you can use NaOH.
Also, you may consider Li(tBuO)3AlH, it is commercial from Aldrich and works up the same way as LAH.
milkshake
September 14, 2008 at 10:14 am
Thank you very much. So I can warm it to RT before quenching.
pmgb
September 14, 2008 at 5:34 pm
I have run many dibal reductions at 0C(ice bath to cool), but the ester was not part of a conjugated system, hence there was no concern about 1,4 addition of hydride. In general i didn’t use dcm either.. I always went with toluene or THF.. most of the time THF. I just used it because I hated crushing up these horrible LAH pellets we had. It is humid were I work, and it sometimes catches on fire because of how reactive the exposed lah is once the pellet is crushed. Dibal was a lot easier to work with because it could be done via syringe.
It turns out that LAH works pretty well for unsaturated ketones. The Li ion i think helps direct attack of the hydride to the carbonyl as opposed to the double bond. I can’t remember the reference, but if you look on scifinder I am sure you can find something.. check out nabh4 vs LAH reduction selectivity in a/b unsat. ketones. I imagine the principle holds true for esters as well.
Tom
September 17, 2008 at 4:30 am
Thank you.
pmgb
September 20, 2008 at 6:16 pm
Hi PMGB,
I was wondering whether my aryl methyl ester compound could be reduced into aldehyde in presence of sulfonamide/carboxamide..
Thanks
Marto
Marto
September 21, 2008 at 6:52 pm
I really dont know. Milkshake might help.
pmgb
September 21, 2008 at 8:22 pm
hi..
I think that it will improve your yeld if you use THF or hexane..but maybe you material is not soluble in hexane, than you could use dry THF…
there is a very nice review about dibal:
http://www.akzonobel-polymerchemicals.com/NR/rdonlyres/CB29DA1C-1144-47F4-888A-B20FC61E17F5/11037/Diisobutylaluminumhydride_ma_row_eng_tb.pdf
take a look..
bye bye
marilia
October 1, 2008 at 12:35 am
Thank you very much Marilia.
pmgb
October 1, 2008 at 3:49 am