MCAT Organic Chemistry Review

Carboxylic Acid Derivatives

9.1 Amides, Esters, and Anhydrides

Amides, esters, and anhydrides are all carboxylic acid derivatives. Each of these is formed by a condensation reaction with a carboxylic acid—a reaction that combines two molecules into one, while losing a small molecule. In this case, the small molecule is water, which is created from the hydroxyl group of the carboxylic acid and a hydrogen associated with the incoming nucleophile.

KEY CONCEPT

In a condensation reaction, two molecules are combined to form one, with the loss of a small molecule—water, in our case. Carboxylic acid derivatives are formed by this mechanism.

DESCRIPTIONS

For each of the carboxylic acid derivatives described in this section, focus on the relevant nucleophile that forms the derivative and the nomenclature of the functional group. In the next section, we’ll focus more directly on the relative reactivity of these compounds.

Amides

Amides are compounds with the general formula RCONR2. They are named by replacing the –oic acid suffix with –amide. Alkyl substituents on the nitrogen atom are listed as prefixes, and their location is specified with the letter N–. Figure 9.1 shows a few examples.

Figure 9.1. Naming Amides

Amides are generally synthesized by the reaction of other carboxylic acid derivatives with either ammonia or an amine. Note that loss of hydrogen from the nucleophile is required for this reaction to take place. Thus, only primary and secondary amines will undergo this reaction.

KEY CONCEPT

Amides are formed by the condensation reaction of other carboxylic acid derivatives and ammonia or an amine.

Cyclic amides are called lactams. These are named according to the carbon atom bound to the nitrogen: β-lactams contain a bond between the β-carbon and the nitrogen, γ-lactams contain a bond between the γ-carbon and the nitrogen, and so forth. Structures of lactams are shown in Figure 9.2.

Figure 9.2. Examples of Lactams

Amides may or may not participate in hydrogen bonding, depending on the number of alkyl groups they have bound, and therefore their boiling points may be lower or on the same level as the boiling points of carboxylic acids.

Esters

Esters are the dehydration synthesis products of other carboxylic acid derivatives and alcohols. They are named by placing the esterifying group (the substituent bound to the oxygen) as a prefix; the suffix –oate replaces –oic acid. Several examples are shown in Figure 9.3. As mentioned in the last chapter, ethyl acetate, derived from the condensation of acetic acid and ethanol, is called ethyl ethanoate according to IUPAC nomenclature.

Figure 9.3. Naming Esters

KEY CONCEPT

Esters are formed by the condensation reaction of carboxylic acids or anhydrides with alcohols.

Under acidic conditions, mixtures of carboxylic acids and alcohols will condense into esters. This reaction, called a Fischer esterification, is shown in Figure 9.4. Esters can also be obtained from the reaction of anhydrides with alcohols.

Figure 9.4. Fischer Esterification

Cyclic esters are called lactones and are named in the same manner as lactams, with the name of the precursor acid molecule also included. Examples are shown in Figure 9.5.

Figure 9.5. Examples of Lactones

Because they lack hydro-gen bonding, esters usually have lower boiling points than their related carboxylic acids.

Triacylglycerols, the storage form of fats in the body, are esters of long-chain carboxylic acids (fatty acids) and glycerol (1,2,3-propanetriol). Saponification is the process by which fats are hydrolyzed under basic conditions to produce soap; saponification of a triacylglycerol is shown in Figure 9.6. Subsequent acidification of the soap regenerates the fatty acids.

Figure 9.6. Saponification of a Triacylglycerol Treating triacylglycerols with NaOH will produce fatty acid salts (soap) as well as glycerol.

Anhydrides

Anhydrides, also called acid anhydrides, are the condensation dimers of carboxylic acids. These molecules have the general formula RC(O)OC(O)R. Symmetrical anhydrides are named by substituting the word anhydride for the word acid in a carboxylic acid. When anhydrides are asymmetrical, simply name the two chains alphabetically, followed by anhydride, as shown in Figure 9.7. Phthalic and succinic anhydrides are cyclic anhydrides arising from intramolecular conden sation or dehydration of diacids; their structures need not be memorized, but recognize them as cyclic anhydrides.

Figure 9.7. Naming Anhydrides

KEY CONCEPT

Anhydrides are usually formed by the condensation reaction of two carboxylic acids.

Acid anhydrides are synthesized, as mentioned previously, by a condensation reaction between two carboxylic acids, with one molecule of water lost in the condensation, as shown in Figure 9.8.

Figure 9.8. Synthesis of an Anhydride via Carboxylic Acid Condensation Two molecules of carboxylic acid come together and lose a molecule of water in the formation of an anhydride.

Certain cyclic anhydrides can be formed simply by heating carboxylic acids, as shown in Figure 9.9. The reaction is driven forward by the increased stability of the newly formed ring; as such, only anhydrides with five- or six-membered rings are easily made. Just as with all anhydride formations, the hydroxyl group of one –COOH acts as the nucleophile, attacking the carbonyl on the other –COOH.

Figure 9.9. Intramolecular Anhydride Formation Heat and the increased stability of the newly formed ring drive this intramolecular ring formation reaction forward.

Anhydrides often have higher boiling points than their related carboxylic acids, based solely on their much greater weight.

MCAT Concept Check 9.1:

Before you move on, assess your understanding of the material with these questions.

1.    For each of the carboxylic acid derivatives below, list the relevant nucleophile that reacts with a carboxylic acid to generate the derivative, the derivative’s suffix, and the name of the derivative in cyclic form.

Carboxylic Acid Derivative

Formed from –COOH by…

Suffix

Cyclic Naming

Amide

     

Ester

     

Anhydride

     

2.    What is the definition of a condensation reaction?