Alcohols

Alcohols to Nitriles

In this article, we will discuss two strategies for converting alcohols to nitriles: 1) Nitriles via substitution, 2) Nitriles via dehydration.

 

Alcohols to Nitriles via Substitution Reactions

To convert an alcohol to a nitrile via substitution, we’ll need to convert the OH into a good leaving group such as a halide, mesylate, or a tosylate, and perform an SN2 substitution using cyanide salt such as NaCN or KCN.

 

 

To convert the alcohol to an alkyl halide, we can react it with HCl, HBr, or HI. The reaction of primary alcohols goes by SN2 mechanism, and secondary alcohols go by both SN2 and SN1 mechanism, whereas tertiary alcohols react by SN1 mechanism. Once we have the alkyl halide, we can react it with KCN and substitute the halogen with CN thus forming the desired nitrile:

 

 

This approach lengthens the carbon chain because the CN group is incorporated into the molecule.

Notice that from the tertiary alkyl halide, the reaction goes by the SN1 mechanism even though the cyanide ion is good nucleophile. This is because tertiary alkyl halides are too sterically hindered to undergo an SN2 substitution, and we use a polar protic solvent to facilitate the ionization of the carbon-halogen bond.

 

Alcohols to Nitriles via Dehydration of Amides

The second approach for converting alcohols to nitriles is the dehydration of amides to nitriles using SOCl2, POCl3, or P2O5:

 

 

So, take a moment to come up with a strategy for converting the alcohol to a primary amide.

 

 

Amides are derivatives of carboxylic acids, so we can oxidize the alcohol to a carboxylic acid and convert the latter to an amide using ammonia with a coupling reagent such as EDC or DCC. Alternatively, we can also convert the carboxylic acid to an acid chloride and react with ammonia.

Let’s put together the summary of this conversation going from an alcohol to a nitrile:

 

 

You can find the details of the reaction between carboxylic acids and amines here.

 

 

Organic Chemistry Reaction Maps

Never struggle again to figure out how to convert an alkyl halide to an alcohol, an alkene to an alkyne, a nitrile to a ketone, a ketone to an aldehyde, and more! The comprehensive powerfull Reaction Maps of organic functional group transformations are here!

 

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