Reduction of nitriles to primary amines with LiAlH4

by James

Description: Lithium aluminum hydride [but NOT sodium borohydride (NaBH4)] can reduce nitriles to primary amines.


The purpose of acid at the end is to protonate the nitrogen in order to give the amine.

Note that 2 or more equivalents of LiAlH4 is best for this reaction.


Notes: Note that the last example is a cyanohydrin, which also works in this reaction.


Addition of hydride ion (H–) from LiAlH4 to the carbon of the nitrile in a 1,2-addition (Step 1, arrows A and B) followed by addition of a second equivalent of hydride (Step 2, arrows C and D) gives an amine anion. When acid is added, the nitrogen is protonated twice to give the neutral amine.

Notes: The choice of Cl as the counter-ion for H3O(+) here is completely arbitrary – it’s just a spectator ion, anyway. Note that it could also be reasonable to use an equivalent of AlH3 formed after Step 1 as the reducing agent in Step 2.


{ 4 comments… read them below or add one }




Matthew Granger

For step 2. Instead of N- getting a second negative charge N (2-), would it first protonate itself once? and then repeat from there until it left?



Hey Matt – although N is drawn with a second negative charge in practice it will be bound to aluminum [an excellent Lewis acid], and the Al-N bond will be quite strong so it’s not as “naked” as it appears. There aren’t really any proton sources present to protonate the nitrogen at this stage until workup.


Matthew Granger

Yeah, that makes sense, basically the electron density of N is being donated to Al, resulting in less anionic nature as observed.
Thanks James!


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