What new things are there to say about sodium borohydride?  Very little, really.  I have to say that I was generally unaware that NaBH4 had utility in the reduction of esters.  The Gray Beast or Lucifer’s Hydride- LiAlH4- has always been the reagent of choice for carboxylates.  But while enroute to other applications of NaBH4, I stumbled upon a few recent references.  This is why I like to browse.

A 2006 article by de Souza in ARKIVOC, reports that aliphatic and aromatic esters are cleanly and rapidly reduced by NaBH4 in methanol/THF.  OK, that’s nice (yawn). Other references to ester reduction can be found dating back at least to Persterfield in 1965 and references therein to 1961.  It’s obviously not new, but I do think that it is relatively obscure.

Reduction of benzylic ketones and alcohols as well as assorted amides in acidc media to form the corresponding -CH2- or N-alkylation product was reviewed by Gribble at Dartmouth in 1998. 

Well, here is the reason for my excitement.  I did some pricing and found that the $/hydride cost of NaBH4 is approximately 25 % that of LiAlH4 at the bulk scale.  That’s a big deal.  What is a bigger deal is that NaBH4 is arguably safer to use than LAH and you can run reactions in water, MeOH, and various combinations of other solvents.  Kill the excess hydride with aq NH4Cl and you’re off to the races.  Though I dearly love and respect LAH, handling bulk material as the solid or as an Et2O or THF soln brings unfortunate hazards to the plant. And, LAH quench can lead to large volumes of pasty aluminate solids that present serious filtration issues. 

I’m sure that a lot of hot shots out there knew this, but it was new to me.  The great breadth of reactivity of NaBH4 as well as its stability to protic solvents provides many useful possibilities for the process chemist. The ability to run a reaction in methanol as opposed to anhydrous ether or THF can provide cost, safety, and competitive advantages for a manufacturer.

1/25/09. Update. US patent 2,765,346 teaches a process wherein Na or K BH4 in THF is treated with LiCl to form a composition that reportedly reduces a variety of esters to the corresponding alcohols. Examples of selective ester reduction are ethyl benzoate, butyl stearate, and ethyl p-nitrobenzoate. While I have not personally tested this process, it seems plausible enought to try.

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