Acid Anhydrides

FIELDS OF STUDY: Organic Chemistry

ABSTRACT

The characteristic properties and reactions of acid anhydrides are discussed. Acid anhydrides are useful compounds in organic synthesis reactions, helping to form complex molecular structures from simple starting materials.

The Nature of Acid Anhydrides

The term "anhydride" indicates the absence of either water or its components, oxygen and hydrogen, from a molecular structure. Acid anhydrides are compounds in which a bond has been formed between two acid functional groups by the virtual elimination of −H from one acid group and −OH from the other. Most common acid anhydrides are formed from carboxylic acids, but they can also be formed from any organic acid and many inorganic acids. Mixed acid anhydrides are also possible and are, in fact, essential components of certain biochemical cycles. Acid anhydrides can also be thought of as esters formed from an acyl group. Generally, acid anhydrides are represented as

The generic placeholders R− and Ar− indicate an alkyl group substituent and an aryl group substituent, respectively.

Acid anhydrides of linear molecules are generally used to add single substituents to a molecular structure. Acid anhydride compounds with a cyclic structure are also commonly used in synthetic procedures to elaborate a molecular structure. In principle, an anhydride can be formed from any carboxylic acid. However, in practice, very few acid anhydrides are available, and other carboxylic-acid derivatives are more readily obtained for particular purposes. Thus, linear carboxylic acids are seldom prepared or utilized. Dicarboxylic acids, in which the formation of the anhydride produces a five- or six-membered ring structure, are more readily converted to their anhydride form and are generally more useful in synthetic methods.

The most common acid anhydride is acetic anhydride. Because of its relative ease of handling and because it does not release hydrogen chloride (HCl) gas as a product of the reaction, it is the preferred reagent for forming acetate esters. In pure form, acetic acid tends to absorb atmospheric moisture. It is a common laboratory practice to add a small amount of acetic anhydride to pure acetic acid to counteract this effect, as any moisture consumed by the hydrolysis of acetic anhydride simply produces more acetic acid, which would not be a contaminant in the reagent.

Formation of Acid Anhydrides

Simple acid anhydrides are never formed by dehydration reactions. Acetic anhydride is produced commercially by the reaction of acetic acid with ethenone in the gas phase, according to the equation

The anhydrides of larger linear carboxylic acids are more difficult to prepare, but in some cases, they can be formed by heating the acid in the presence of a strong dehydrating agent, such as phosphorus pentoxide (P₂O₅), and separating the anhydride from the reaction mixture as it forms. Cyclic anhydrides such as maleic anhydride and succinic anhydride form readily when their parent acids are heated. The process is assisted by the removal of water from the reaction as it is formed, which prevents the reverse reaction from occurring. Ring size is vitally important for this process: five- and six-membered rings are well suited to the geometric constraints of the electron orbitals in carbon and oxygen atoms, while seven-membered rings are more difficult to form because of the strain that the bond angles of such a ring impose on the molecule. Adipic acid, or 1,6-hexanedioic acid, does not form the corresponding cyclic anhydride; instead, it eliminates a molecule of both carbon dioxide and water to produce the less strained compound cyclopentanone.

Reactions of Acid Anhydrides

Acid anhydrides are reactive compounds widely used for the formation of esters. By far the most common commercial use of acetic anhydride is in the formation of acetate esters of carbohydrate compounds such as sugars, starches, and celluloses. The carbonyl (C=O) groups of an acid anhydride readily interact with nucleophiles, which are chemical species that are attracted to positively charged species. This happens partly because the electronegative oxygen atoms of the carbonyl groups tend to draw electron density away from the carbon atoms, causing the carbon to behave as though it were positively charged, and partly because the way the bonds are arranged around the carbon atoms makes it easier for nucleophiles to approach and interact. After the nucleophile is added and the leaving group is eliminated, the carbonyl groups re-form in the new molecule. This same basic mechanism permits acid anhydrides to be converted into different acid derivatives. Reaction with water reconverts the anhydride into its acid form, which allows other types of reactions to occur after an anhydride group has been added to a substrate molecule. For example, maleic anhydride is commonly used in a Diels-Alder reaction, which is a type of reaction that results in the addition of a six-membered ring structure to the substrate molecule. Hydrolysis of the resulting molecule produces two carboxylic acid functional groups (−COOH) that can be modified by other reactions to produce a desired product.

Acid anhydrides also react well with ammonia to produce the corresponding amide of one carboxylic acid group and the ammonium salt of the other. The reaction of acetic anhydride with ammonia, for example, would produce acetamide and ammonium acetate, as seen below:

A reaction with a substituted amine such as ethylamine would produce the corresponding substituted amide compound.

Anhydrides are also able to act as acylating agents in the Friedel-Crafts acylation of benzene and benzene-like aromatic compounds. One half of the anhydride function bonds chemically to the aromatic ring as an acyl substituent, while the other half is reconverted into the acid. The reaction is typically catalyzed by a Lewis acid, such as aluminum trichloride (AlCl₃) or ferric chloride (FeCl₃). Phthalic anhydride, for example, can be used to acylate benzene, producing the corresponding benzoic acid derivative, according to the equation

Diels-Alder, Friedel-Crafts, and similar reactions are useful in organic synthetic chemistry because they allow the chemist to easily and quickly build a complex molecular structure from very simple starting materials. The reactions typically produce hydrogen chloride as well, but this is an inconsequential by-product and is seldom, if ever, shown in structural formula equations.

Nomenclature of Acid Anhydrides

Acid anhydrides are named according to the parent acid from which they are formed, simply by adding "anhydride" to the name of the parent acid. Accordingly, the anhydride of butyric acid would be named butyric anhydride, while maleic acid and succinic acid readily form maleic anhydride and succinic anhydride. Mixed anhydrides, though uncommon, are also known. For a mixed anhydride, the names of the two parent acids are used, with the "higher" acid being named in second place. For example, the mixed anhydride of acetic acid and phosphoric acid would be named acetic phosphoric anhydride. Such mixed anhydrides sometimes appear in enzyme-mediated biochemical processes.

PRINCIPAL TERMS

• acyl group: a functional group with the formula −RCO, where R is connected by a single bond to the carbon atom of the carbonyl (C=O) group.
• carboxylic acid: an organic compound containing a carboxyl functional group and having the general formula RC(=O)OH.
• functional group: a specific group of atoms with a characteristic structure and corresponding chemical behavior within a molecule.
• organic acid: an acid derived from an organic compound.
• R (generic placeholder): a symbol used primarily in organic chemistry to represent a hydrocarbon side chain or other unspecified group of atoms in a molecule; can be used specifically for an alkyl group, with Ar used to represent an aryl group.

Bibliography

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