Reagent Friday: Sodium Borohydride (NaBH4)
Last updated: January 29th, 2020 |
Sodium Borohydride (NaBH4) For Reduction Of Aldehydes And Ketones (And Demercuration)
In a blatant plug for the Reagent Guide, each Friday I profile a different reagent that is commonly encountered in Org 1/ Org 2. Version 1.2 just got released, with a host of corrections and a new page index.
Having just talked about the oxidation ladder, it makes sense to start going into reagents for oxidation and reduction reactions.
Sodium borohydride (NaBH4)
What it’s used for: Sodium borohydride is a good reducing agent. Although not as powerful as lithium aluminum hydride (LiAlH4), it is very effective for the reduction of aldehydes and ketones to alcohols. By itself, it will generally not reduce esters, carboxylic acids, or amides (although it will reduce acyl chlorides to alcohols). It is also used in the second step of the oxymercuration reaction to replace mercury (Hg) with H.
Similar to: lithium aluminum hydride (LiAlH4) although less reactive.
Reduction Of Aldehydes And Ketones With NaBH4
For our purposes, sodium borohydride is really useful for one thing: it will reduce aldehydes and ketones. In this sense it traverses one rung on the oxidation ladder. Here are some examples of it in action.
Notice the pattern: we are breaking a C-O bond and replacing it with a C-H bond. This is what helps us classify the reaction as a reduction.
Note that we also form an O-H bond. This is where textbooks and other sources are sometimes not as clear as they should be: in order to make the alcohol, the oxygen needs to pick up a proton (H+) from either water or acid that is added after the reaction is complete (note: this is often referred to as the workup).
Sodium Borohydride For “Demercuration” (The Second Step Of Oxymercuration-Demercuration)
NaBH4 also makes an appearance in the oxymercuration reaction. Specifially, NaBH4 is used in the second step of the reaction, to break the C-Hg bond and turn it into a C-H bond.
Mechanism For The Reduction Of Aldehydes And Ketones With NaBH4
How it works: The mechanism of the reaction of sodium borohydride with aldehydes and ketones proceeds in two steps. In the first step, H(–) detaches from the BH4(–) and adds to the carbonyl carbon (an example of [1,2]-addition). This forms the C-H bond, and breaks the C-O bond, resulting in a new lone pair on the oxygen, which makes the oxygen negatively charged (FYI: we call these negatively charged oxygens alkoxides, as they are deprotonated alcohols). In the second step, a proton from water (or an acid such as NH4Cl) is added to the alkoxide to make the alcohol. This is performed at the end of the reaction, a step referred to as the workup.
I suppose I should also mention that NaBH4 will reduce acyl halides to alcohols, but things are a little lengthy here already.
Note: this mechanism assumes a polar protic solvent. What if you use a slightly different solvent? You have a slightly different mechanism, see note below.
I also won’t go into the detailed arrow pushing for NaBH4 in the oxymercuration reaction. But the key point is that the carbon-mercury bond is broken, and a new carbon hydrogen bond is formed, and it is NaBH4 which performs this reaction. It works out like this:
P.S. You can read about the chemistry of NaBH4 and more than 80 other reagents in undergraduate organic chemistry in the “Organic Chemistry Reagent Guide”, available here as a downloadable PDF.
A note about the mechanism.
The mechanism drawn above works in a polar protic solvent like methanol, which can protonate the alkoxide. What happens if you use a non-protic solvent like DMF? Well, since you don’t have a proton source, you form a salt! It would look something like this:
This article has more detail:
Reduction of ketones by sodium borohydride in the absence of protic solvents. Inter versus intramolecular mechanism.
Kayser, M., Eliev, S., & Eisenstein, O.
Tetrahedron Letters, 1983 24(10), 1015–1018.
(Advanced) References and Further Reading:
- First example
Brown, H.C.; Wheeler, O.H.; Ichikawa, K.
Tetrahedron 1:214 (1957)
Early paper by Nobel Laureate H. C. Brown describing the reactivities of simple aldehydes and ketones to reduction by NaBH4, in which it is shown that aldehydes are more reactive than ketones to nucleophilic reactions.
- Mechanistic studies
Brown, H. C.; Ichikawa, K.
Tetrahedron 1:221 (1957)
This paper and the above are both mechanistic studies on the reduction of carbonyls – this paper investigates the effect of ring size on the reduction of cyclic ketones (e.g. reduction of cyclobutanone vs. cyclopentanone, cyclohexanone, etc.).
- Reference To An Experimental Procedure
Antonio Bermejo Gómez, Nanna Ahlsten, Ana E. Platero-Prats and Belén Martín-Matute
Org. Synth. 2014, 91, 185
The first step in this procedure uses NaBH4 to reduce a cinnamyl ketone to the alcohol.