NITRIL

Reduction of nitriles to primary amines with LiAlH4

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

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

SN2 of Cyanide with Alkyl Halides to give Nitriles

Description: Alkyl halides (or tosylates) will react with cyanide ion to give alkyl cyanides (nitriles)
Notes: X here is a halide (Cl, Br, I) or sulfonate (OTs, OMs, OTf). Any alkali metal can be used (Li, Na, K…) as the counter-ion for the CN. For our purposes the exact identity is unimportant.

Notes: Note that since this is an SN2 reaction and proceeds via backside attack, there will be inversion of configuration at the carbon (note the last two examples).
Mechanism: In the SN2 reaction the nucleophile CN(-) attacks the carbon with the good leaving group (C-1 in this case), displacing chloride ion int this example (Step 1, arrows A and B). The reaction is concerted, meaning both steps occur at the same time.




Notes: As with all SN2 reactions, the reaction is facilitated by a polar aprotic solvent such as DMSO, acetone, or acetonitrile.