Carboxylic acids are defined by the carboxyl group -COOH, in which a carbonyl and a hydroxyl share the same carbon. They are named with the suffix -oic acid (ethanoic acid) and the conjugate base salts or esters take the -oate suffix (acetate, ethyl acetate). Acidity arises from the resonance stabilization of the carboxylate anion, which delocalizes the negative charge over both oxygens. In IR spectroscopy they show a characteristically very broad O–H stretch from 2500–3300 cm\(^{-1}\) that overlaps C–H stretches, plus a strong C=O stretch near 1710 cm\(^{-1}\). Because each -COOH contains both a hydrogen-bond donor and acceptor, two acid molecules form a cyclic hydrogen-bonded dimer, giving carboxylic acids unusually high boiling points. In \(^1\)H NMR the O–H protons appear far downfield at 10–13 ppm and are often broad due to hydrogen bonding. Fischer esterification, an acid-catalyzed reaction with an alcohol that releases water, converts a carboxylic acid into an ester; Le Chatelier's principle—using excess alcohol or removing water—drives the equilibrium toward ester. Treatment with \(SOCl_2\) or \(PCl_5\) converts a carboxylic acid into an acid chloride, while reduction with \(LiAlH_4\) reduces it all the way to a primary alcohol. Decarboxylation—loss of \(CO_2\)—is especially favorable when a beta-keto or beta-carboxyl group is present.
Esters are structured R-CO-O-R′ and named as alkyl alkanoates (for example, ethyl acetate). Their IR spectra show two strong C–O stretches near 1200 and 1250 cm\(^{-1}\) plus a C=O stretch near 1735–1750 cm\(^{-1}\)—higher than that of ketones due to the electron-withdrawing alkoxy oxygen. Saponification is the base-catalyzed hydrolysis of an ester to a carboxylate salt plus an alcohol; this is the chemistry behind converting triglycerides—triesters of glycerol and long-chain fatty acids—into soap. Reaction of an ester with two equivalents of a Grignard reagent produces a tertiary alcohol via a ketone intermediate, while reduction with \(LiAlH_4\) gives a primary alcohol (from the acyl portion) plus the alcohol corresponding to the -OR group. Transesterification is the exchange of the -OR group with a different alcohol under acid or base catalysis. Aspirin (acetylsalicylic acid) is a familiar example of a molecule containing both a carboxylic acid and a phenolic ester installed by acetylation.
Amides contain a carbonyl bonded to nitrogen (R-CO-NR′₂) and use the suffix -amide (ethanamide, acetamide). Resonance delocalization of the nitrogen lone pair into the carbonyl gives the C–N bond partial double-bond character, making it shorter and stronger with restricted rotation, and dramatically reduces the basicity and nucleophilicity of the nitrogen compared with amines. IR spectra show the amide I band (C=O stretch) at 1630–1700 cm\(^{-1}\)—lower than esters and ketones because of resonance donation from N—and N–H stretches near 3300 cm\(^{-1}\) when an N–H is present. Hydrolysis of an amide yields a carboxylic acid and an amine (or carboxylate and ammonium salt under base), while reduction with \(LiAlH_4\) gives an amine by full reduction of the C=O. The Hofmann rearrangement uses \(Br_2/NaOH\) to degrade a primary amide to a primary amine with one fewer carbon. Cyclic amides are called lactams, with the four-membered beta-lactam ring of penicillin being a strained, hydrolytically reactive example of biological importance.
Anhydrides join two acyl groups through an oxygen (R-CO-O-CO-R′) and are named as '-oic anhydrides' (ethanoic anhydride, also called acetic anhydride). Their IR spectra show two C=O stretches near 1750 and 1820 cm\(^{-1}\), split by symmetric/asymmetric coupling, and they are more reactive than esters because the carboxylate leaving group is better than an alkoxide. Reaction of acetic anhydride with an amine yields an amide plus acetic acid as a byproduct—the route by which amines are acetylated in syntheses such as acetaminophen or aspirin. Acyl (acid) chlorides carry a carbonyl bonded to a halogen (R-CO-X), most commonly chloride, and are named as '-oyl chlorides' (ethanoyl chloride, also called acetyl chloride). They are the most reactive common carboxylic acid derivative because chloride is an excellent leaving group and strongly activates the carbonyl carbon. The general reactivity order toward nucleophilic acyl substitution is acyl halide > anhydride > ester > amide, reflecting leaving-group ability. Nucleophilic acyl substitution proceeds by a two-step addition–elimination mechanism: the nucleophile adds to the carbonyl carbon to form a tetrahedral intermediate, then the leaving group departs to regenerate the C=O. This pathway is open to carboxylic acid derivatives because they bear a leaving group on the carbonyl carbon; simple aldehydes and ketones lack such a group and therefore undergo only nucleophilic addition.