20.5 Preparing Carboxylic Acids

Synthesis of Carboxylic Acids

There are several reliable ways to prepare carboxylic acids, each starting from a different functional group. Knowing which route to use depends on your starting material and whether you need to add a carbon atom to the chain. This section covers three major methods: nitrile hydrolysis from alkyl halides, oxidation of alcohols and aldehydes, and the Grignard reaction with $CO_2$.

Carboxylic Acids from Alkyl Halides (via Nitriles)

This is a two-step process that converts an alkyl halide into a carboxylic acid with one additional carbon atom. That extra carbon comes from the cyanide ion, which makes this route especially useful when you need to extend a carbon chain by one.

Step 1: Form the nitrile. Treat the alkyl halide with sodium cyanide ($NaCN$) or potassium cyanide ($KCN$). The cyanide ion ($CN^-$) acts as a nucleophile in an $S_N2$ reaction, displacing the halide.

$R\text{-}X + CN^- \rightarrow R\text{-}C\equiv N + X^-$

This works best with primary (and some secondary) alkyl halides. Tertiary substrates will undergo elimination instead.

Step 2: Hydrolyze the nitrile. Heat the nitrile with water under either acidic or basic conditions to break the $C\equiv N$ triple bond and produce the carboxylic acid.

• Acidic hydrolysis (e.g., aqueous $HCl$ or $H_2SO_4$, heat):

$R\text{-}C\equiv N + 2H_2O \xrightarrow{H^+} R\text{-}COOH + NH_4^+$

• Basic hydrolysis (e.g., aqueous $NaOH$, heat, then acidify):

$R\text{-}C\equiv N + H_2O \xrightarrow{OH^-} R\text{-}COO^- + NH_3$

$R\text{-}COO^- + H^+ \rightarrow R\text{-}COOH$

Under basic conditions you initially get the carboxylate salt, so an acid workup is needed to protonate it to the free carboxylic acid.

Oxidation of Alcohols and Aldehydes

Primary alcohols can be oxidized all the way to carboxylic acids using strong oxidizing agents such as $KMnO_4$, $H_2CrO_4$ (Jones reagent), or $Na_2Cr_2O_7$ with $H_2SO_4$. The oxidation passes through the aldehyde stage but doesn't stop there under these vigorous conditions:

$R\text{-}CH_2OH \xrightarrow{[O]} R\text{-}CHO \xrightarrow{[O]} R\text{-}COOH$

If you only wanted the aldehyde, you'd need a milder, selective oxidant like PCC. But for carboxylic acid preparation, the strong oxidants are exactly what you want.

Aldehydes themselves are easily oxidized to carboxylic acids because the $C\text{-}H$ bond on the carbonyl carbon is relatively weak. Even mild oxidizing agents can do the job:

• Tollens' reagent ($Ag(NH_3)_2^+$) oxidizes the aldehyde while depositing a silver mirror.
• Jones reagent ($CrO_3$ in aqueous $H_2SO_4$) also works well.

$R\text{-}CHO \xrightarrow{[O]} R\text{-}COOH$

Note that secondary alcohols oxidize to ketones, not carboxylic acids. And tertiary alcohols resist oxidation altogether under normal conditions. This selectivity matters when choosing your synthetic route.

Carboxylic Acids from Grignard Reagents

Like the nitrile route, the Grignard approach adds one carbon to the chain. The extra carbon comes from $CO_2$ this time.

Step 1: React the Grignard reagent with $CO_2$. The highly nucleophilic carbon of the Grignard reagent ($R\text{-}MgX$) attacks the electrophilic carbon of carbon dioxide in a nucleophilic addition:

$R\text{-}MgX + CO_2 \rightarrow R\text{-}COOMgX$

The product at this stage is a magnesium carboxylate salt.

Step 2: Acid workup. Treat the salt with dilute aqueous acid (e.g., $HCl$) to protonate the carboxylate and give the free carboxylic acid:

$R\text{-}COOMgX \xrightarrow{H_3O^+} R\text{-}COOH$

This method is versatile because you can choose your Grignard reagent to target a specific carboxylic acid. For example, reacting phenylmagnesium bromide ($C_6H_5MgBr$) with $CO_2$ followed by acid workup gives benzoic acid ($C_6H_5COOH$).

Remember the standard Grignard caution: the reaction must be run under anhydrous conditions (no water, no protic solvents) because Grignard reagents react violently with water and are destroyed by it.

Choosing the Right Method

When deciding which preparation to use, consider:

• Need to extend the carbon chain by one? Use the nitrile route (from alkyl halides) or the Grignard + $CO_2$ route.
• Already have a primary alcohol or aldehyde with the right number of carbons? Oxidation is the most straightforward path.
• Starting from an aryl halide? The Grignard route works well here, since aryl halides can form Grignard reagents but don't undergo $S_N2$ with cyanide.