1.12: Carboxylic acids (2023)

Oxidation of primary alcohols

There are two types of reactions that carboxylic acids can generate. We will first look at those that depend on the oxidation of lower oxidation state groups (less oxygen, more hydrogen). So we will see that on the way to the formation of a carboxylic acid there are reactions that form a carbon-carbon bond.

As you can imagine, carboxylic acids can be produced by oxidizing less oxidized groups. The most important of these is the group of primary alcohols. A typical reaction is:

We recognize the oxidizing agent potassium dichromate as the same reagent used to oxidize aldehydes to carboxylic acids. Chromium is in the sixth oxidation state in dichromates and therefore is reduced to the third oxidation state. The details of chromate reduction are complex and will not be covered here. The oxidation of aldehydes also produces carboxylic acids, but because aldehydes are less easy to prepare than carboxylic acids, this process is not widely used.

Oxidation of side chains in aromatic rings

Another oxidative process does not initially appear to involve a functional group. Alkyl groups (usually methyl groups) attached directly to an aromatic ring are also oxidized to carboxylic acids. Since the methyl group contains only C-H sigma bonds, this does not seem to be a likely site for the reaction. However, it is influenced by the neighboring aromatic ring, which is why the reaction takes place. This is somewhat similar to the particular reactivity of the alpha C-H bonds of a ketone or aldehyde. Here is an example:

Remember this reactionrequiresthe presence of an aromatic ring close to the alkyl group to be oxidized. Every carbon beyond the first is lost in this process, which is one of the few reactions that breaks a carbon-carbon bond.

form a carbon-carbon bond

There are two sequences of reactions that form carbon-carbon bonds on the way to carboxylic acids. The first is another use of the Grignard reagent. Remember that Grignard reagents react with carbonyl compounds to form alcohols. Although we don't normally think of it that way, carbon dioxide is a carbonyl compound (O=C=O). When a Grignard reagent is used to supply a nucleophilic carbon atom to the carbonyl carbon of carbon dioxide, we obtain a carboxylic acid (after quenching with aqueous acid).

The attack of the Grignard reagent on carbon dioxide is directly analogous to the same step in the reactions of other carbonyl compounds:

Here is the complete sequence in the more compact format we used for the Grignard complements above:

Notice that the product has one more carbon than the bromoalkane we started with, and that carbon is in a carboxylic acid group.

There is also another way to make a new carbon bond and end up with a carboxylic acid. If we have a primary alkyl halide (primary means that the carbon attached to the halogen is only attached to one other carbon atom, its other two bonds to hydrogen), we can react with sodium cyanide. The cyanide ion will replace the halogen and this will form a new carbon-carbon bond. The product is called nitrile. Its carbon-nitrogen triple bond can be hydrolyzed with aqueous acid to produce a carboxylic acid. The order is as follows (usually the nitrile is isolated and then hydrolyzed in a separate reaction):

We will not now go into the details of the mechanisms of any of these reactions. You can usefully speculate about nitrile hydrolysis. You can start by thinking of the C-N triple bond as a carbonyl group. Finally, it contains a pi bond between the carbon and an electronegative atom, similar to the pi bond in a carbonyl group.

acid and base forces

The remaining problem with carboxylic acids is understanding why they are acidic. We can taste its acidity by tasting vinegar, which is a diluted solution of acetic acid in water. The Lowry-Bronsted acid model is suitable for this. Let's refresh our memory of this model and the interpretation of the pK term_A.

According to the Lowry-Bronsted model, when we think of acids, we think of a molecule that can donate a proton (H⁺). A base is a molecule that can accept a proton (using the electron pair that is the defining characteristic of a Lewis base). Stronger acids readily donate protons to stronger bases. The products of this transaction are weaker acids and bases. Here's the pattern.

In particular, note that a strong acid is strong because it voluntarily donates a proton. This means that its conjugate base (the base that remains after the proton leaves) is weak. Because if the base was strong, it would take the proton back and the acid couldn't donate it. When we call an acid strong by saying it has a small pKa_A, we also say that its conjugate base is weak. HCl is a strong acid (pK_A-7). When we say this, we also say that Cl^-it is a weak foundation. The conjugate base of an acid whose pKa_Ais small or negative is a weak base. This means we can use a pK_ATable like Table 2.1 on page 43 of Brown to track acidity (strong acids have small or negative pKa_A's) and basicity (weak bases come from strong acids with small or negative pKa_A'S).

Carboxylic acid acidity - carboxylation basicity

It also means we can rephrase the question, "Why carboxylic acids?" say "Why are the conjugate bases of carboxylic acids such weak bases?" To put this in context, note that carboxylic acids have pK_Aof about 5, while water and alcohols have pKa_Aof about 16. What makes the conjugate base (we call it carboxylation) of a carboxylic acid so weak compared to a hydroxide (OH^-) alcoholic egg (RO^-) Pure?

As usual, we will try to find our explanations in the structure. There is an obvious difference between a carboxy ion and an alkoxide ion. The carboxy ion has two electronegative oxygen atoms versus just one for the alkoxide ion. These electronegative atoms would hold the electron pairs tighter, meaning the electron pairs would be less available to bond with a proton. Fewer available electron pairs mean a weaker base.

This explains some of the weakness of carboxylate ions as bases, but there is also a more subtle feature. Note that we can move electrons between pi bonding situations and unshared pairs without changing the structure of the carboxylation. We see this as a resonance and see that it lowers the energy of a carboxylation compared to that of an alkoxide ion, where such a resonance is not possible. Lower energy means more stable, more malleable and less reactive, which results in a weaker base. Consequently, the conjugated carboxylic acid is stronger than one whose conjugate base has no possibility of resonance.

The somewhat paradoxical result of this is that carboxylic acids are stronger acids than alcohols because carboxylate ions, their conjugate bases, are weaker bases than alkoxides. This is largely due to resonance stabilization of carboxy ions, which cannot occur in alkoxides.

This understanding of the structure of carboxyl ions also helps us understand why, when a Grignard reagent reacts with carbon dioxide, only one of the two carbonyl groups reacts. The product of this reaction is a carboxylation. It is resonance stabilized, so the "real" structure is halfway between the two resonance structures. This means that each C-O bond is halfway between a single bond and a double bond, that is, one and a half bonds. Such a bond would be much less reactive than the double bond of a carbonyl group, so it is not surprising that the Grignard reagent would react with carbon dioxide rather than the carboxylate ion.