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. 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).
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.
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.
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.
The Hofmann and Curtius Rearrangements
Reducing Sugars
Cyclic Dienes and Dienophiles in the Diels-Alder Reaction
Reductive Amination
The Diels-Alder Reaction
3 Trends That Affect Boiling Points
What Makes A Good Nucleophile?
Five Key Factors That Influence Acidity
Polar Protic? Polar Aprotic? Nonpolar? All About Solvents
Table of Functional Group Priorities for Nomenclature
{ 11 comments… read them below or add one }
What does the reaction between sodium borohydride and copper II oxide look like?
Hi James: in the ACS study guide (for the ACS organic exam) they state that NaBH4 “reduces ketones to secondary alcohols but does not react with alkenes.” My textbook (McMurry) says that “unsaturated ketones often undergo overreduction with NaBH4 to give a mixture of both unsaturated alcohol and saturated alcohol.”
I will go with the ACS guide’s interpretation of reality for the exam, I guess, but which source is correct?
Thank you!
In Org 2 you learn about “conjugate addition” (like the Michael reaction) where nucleophiles add to alkenes adjacent to a carbonyl. NaBH4 can do “conjugate addition” as well. However conjugate addition only occurs when there is a good electron withdrawing group adjacent to the alkene. It doesn’t work for, let’s say, butene.
Thank you, James!
Can NaBH4 reduce benzoic acid to benzaldehyde?
No, it can only reduce aldehydes and ketones. To reduce benzoic acid to benzaldehyde, you’d need to either: 1) treat with LiAlH4 to get the alcohol, then treat with PCC, Swern, or DMP to get the aldehyde. Or 2) use SOCl2 to make the acid halide, then reduce to the aldehyde with LiAlH(OtBu)3
Can NaBH4 reduce Beta-keto sulfones to B-hydroxy sulfones.
plz suggest mi
Yep, I would expect that it could. Although the ketone will be spending a considerable amount of time in the enol form.
What should be the molar ratio while using NaBH4 on commercial production of a molecule to be converted to alcohol?
e.g acetophenone to corresponding alcohol
Slight excess, e.g. 1.1 equivalents.
My professor said NaBH4 does not reduce esters but can reduce lactones which are cyclic esters. What is the reason for that?