Dibal-h Chemistry

[Pierpont Oldham]

Likemost organoaluminum compounds, the compound's structure is most probably more than that suggested by its empirical formula. A variety of techniques, not including X-ray crystallography, suggest that the compound exists as a dimer and a trimer, consisting of tetrahedral aluminium centers sharing bridging hydride ligands.[2] Hydrides are small and, for aluminium derivatives, are highly basic, thus they bridge in preference to the alkyl groups.

DIBAL is useful in organic synthesis for a variety of reductions, including converting carboxylic acids, their derivatives, and nitriles to aldehydes. DIBAL efficiently reduces α-β unsaturated esters to the corresponding allylic alcohol.[1] By contrast, LiAlH4 reduces esters and acyl chlorides to primary alcohols, and nitriles to primary amines [using Fieser work-up procedure]. DIBAL reacts slowly with electron-poor compounds, and more quickly with electron-rich compounds. Thus, it is an electrophilic reducing agent whereas LiAlH4 can be thought of as a nucleophilic reducing agent.

Although DIBAL reliably reduces nitriles to aldehydes, the reduction of esters to aldehydes is infamous for often producing large quantities of alcohols. Nevertheless, it is possible to avoid these unwanted byproducts through careful control of the reaction conditions using continuous flow chemistry.[4]

Sometimes it only take a coffee to allow the Rochelle's salt to do it's thing - other times it can take overnight. I stick with the semi-aqueous workup most times - and I've done some pretty huge LAH reduction. The real bastard was a reduction of butyne-1,4-diol to the alkene. I'd normally go through an entire 1L bottle of LAH solution.

I just wanted to let you know that your posts are greatly appreciated. They may be necessarily infrequent, but I have learned several quite useful things from Curly Arrow and look forward eagerly to each one.

Your dry column vacuum chromatography technique alone has saved me many hours of tedium!

Couple of comments about your set-up, as shown in the pic.

You need a lab jack and a cork ring.

Dunno if the comment is helpful or irritating: trying to be the former; apologies if I'm being the latter.

@Daniel

German? - No.

Why lab jack? To be able to quickly apply either coolant and hence hold exotherm, or empty bowl to stop the the liquors spilling onto the f/c. Standard practice wherever I've worked.

Gyges, I was also taught to do chemistry like that. I do tend to have a crystallisation dish under my flask to collect my compound in case of breakage. However, with the possible exception of removing a heating source I generally haven't found lab jacks particularly useful under my stirrer. I don't think there is anything fast about a lab jack. The models I have encountered tend to be rather slow and involve a fair bit of twisting. I find readjusting the clamp to be a much faster process. Anyway, enough of this. I am a firm believer in "whatever works for you" as long as it doesn't pose any danger to your surroundings. D!

krest17, yes this is one of the alternative methods that I referred to that works really well too. I also can't remember the exact conditions but I know that this work-up procedure can be found in the following paper: Skouroumounis, G.; Winter, B. Helv. Chim. Acta 1996,

79, 1095.

I'll look it up when I'm back at work on Monday, if someone doesn't beat me to it. Have a nice weekend chemists. D!

hm... that's new to me with Rochelle's salt. i did some low valent titanium reduction (TiCl4 with Zn dust) which give during work up also a mess of black/grey stuff. i broke this suspension with a mixture of citric acid/ammonium acetate which worked very well too.

currently i have some problems with braking up a hydrolised ZnI2 suspension... tried it with citric acid too but it didn't work... maybe you have some ideas?

I've done a few LAH reductions and always use the Fieiser workup.

And for DiBAl, quench with EtOAc, then add saturated tartaric acid solution, works better than Rochelle's.

Can also use citric acid to solubilise aluminium salts.

I did DIBALH reaction on few analogues and I had problems with it too:

-troubleshooting.html

On the other hand, I reduced ester and amide on the same compound with classic rx with DIBALH, but only all amide was reduced to amine and very little ester reduced to alcohol.

Why is that?

At the end of the day, I collected the esters and did transesterification with methoxide to get desired alcohol as the side product.

Never owned a lab jack, but could see how it'd help. I tend to do a lot of heating using tin foil tipi's as opposed to oil baths. That way, if things get over excited, I can flick the plate off and whip the foil away and it'll cool in a controllable manner (particularly if I'm not roasting the plate to full in the first place). Also, no spills, no fires, no slippery glass, doesn't smell like an old chippy that's failed all of it's last health inspections etc.

I use a ball and socket if I need to support heavy flasks or stretches of glass, so the run can be 'bent' to be clamped (without fiddling for ages for a semi-decent results) or rest in the right place (minus a jack). Even with the clamp tight, there is still enough flexibility to save the glass in some accidental knocks, as it can move a little.

I would certainly have a cork ring under that though. But then, I bet that rail behind the glass is bolted to the hood and not going anywhere fast.

My most annoying glassware problems as of late was watching all the keck clips disintegrate and then ping off my glass when porting reactive gases around (despite them being QuickFit and lined with Krytox).

PTFE.

Quenching with EtOAc can be risky. If your alcohol is unhindered enough, you can transesterify the EtOAc to get some acyl protected alcohol. I quenched with EtOAc for the reduction of undecanoic acid and ended up with 44% acyl protected alcohol.

Hello everyone. I am currently working on a reduction using LiAlH4 and AlCl3. Does anyone have experience which workup works best for this combo? So far I've tried: 1. quenching with HCl, then extraction.

2. Fieser workup.

I feel like both aren't perfect. Thanks a lot in advance!

Hello,

I will be doing my first LiAlH4 reduction pretty soon, fingers crossed this week. I have been trying to do some reading to prep and have in my head the procedures so I don't fumble in the midst of it all. Do you happen to know of any good videos or readings I can look up? I will be using a manifold. Any help would be Appreciated!! THANK YOU! :)

Hello,

I will be doing my first Lithumiun Al. Hydride Reduction this week, Fingers Crossed!! I have been trying to do some prep work to figure out what exactly I will be doing procedure wise so I don't fumble in the midst of it all. I came across this blog with my online adventure of LiAlH4 Reduction. If you happen to know of any good youtube videos or papers I could read it would be much appreciated!! I am planning on using a manifold as my setup. THANK YOU!! ps: I am not sure if this comment will be posted twice, I did not see if the first time I posted it so I tried again....

Hello all,

I used LiAlH4 to reduce an epoxide. Has any one done this ? and did it work? If it worked, can you please give me some details , like the amount that you used, the time it had taken to form the products... etc

Thanks

Thank you for this post, Curly, I found some nice advice reading it !

I am struggling with one specific LAH reduction.

N-Boc tyramine is reduced by LAH in 1,4-dioxane. Work in a real pain.

N-methyl tyramine combine high solubility in water, basic center (NHMe) and a phenol... I've tried almost every work-up I could find and none give me the desired product, pure enough. (I can't run a chromatography on it, it's way to polar... )

Any advice from you or any reader please ?

So, I will argue that quenching the hydride with EtOAc is a rather bad idea when reducing molecules containing an amine functional group. It is better to use H2O or if you dont want H2, then another non-protic solvent that will not react with the amine.

In my case I wanted to methylate a primary amine. So I did the formylation and then the reduction with LiAlH4. I then quench the reaction with EtOAc which was reduced to ethanal and before going to ethanol reacted with my amine to give the imine which was then reduced to a nice byproduct. So I got a methyl, ethyl amine...quite the byproduct I say.

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