Premed · Premed · Organic Chemistry 2
Lecture 8: Carboxylic Acids: Synthesis and Reactions
Organic Chemistry II
Learning Objectives
By the end of this lecture, students will be able to:
- Describe the structure, bonding, and physical properties of carboxylic acids
- Explain the acidity of carboxylic acids and factors that affect pKa
- Name carboxylic acids using IUPAC and common nomenclature
- Describe key synthetic methods for preparing carboxylic acids
- Write mechanisms for reactions of carboxylic acids including reduction, decarboxylation, and conversion to acid derivatives
- Identify carboxylic acids by spectroscopic methods
Lecture Content
I. Structure, Bonding, and Physical Properties
The carboxyl group (-COOH) combines a carbonyl and a hydroxyl group on the same carbon. The carbonyl carbon is sp2 hybridized, and resonance interaction between the C=O and C-OH portions gives partial double-bond character to the C-OH bond.
Carboxylic acids exhibit remarkably high boiling points, even higher than those of alcohols of comparable molecular weight. This is because two carboxylic acid molecules form a cyclic dimer stabilized by two strong O-H...O=C hydrogen bonds. Acetic acid, for example, boils at 118 degrees C, compared to 78 degrees C for ethanol, despite similar molecular weights. The lower members of the series (C1 through C4) are miscible with water, and carboxylic acids in general have distinctive sharp, sour odors -- acetic acid smells of vinegar, and butanoic acid of rancid butter.
In IUPAC nomenclature, carboxylic acids are named by replacing the -e ending of the parent alkane with -oic acid, and the carboxyl carbon is always designated C1. Common examples include methanoic acid (formic acid), ethanoic acid (acetic acid), propanoic acid, and benzoic acid. Dicarboxylic acids have their own set of well-known common names: oxalic (C2), malonic (C3), succinic (C4), glutaric (C5), and adipic (C6). The Greek letter system designates the carbon adjacent to the carboxyl as alpha, the next as beta, and so on.
II. Acidity of Carboxylic Acids
Carboxylic acids are remarkably acidic for organic compounds, with typical pKa values of 4 to 5. Formic acid has a pKa of 3.75, acetic acid 4.76, and benzoic acid 4.20. This acidity, roughly 10^11 times greater than that of a typical alcohol (pKa around 16), is explained by the resonance stabilization of the carboxylate anion (RCOO-). The negative charge is delocalized equally over both oxygen atoms through two equivalent resonance structures, and both C-O bonds become identical with a bond order of 1.5. Alkoxide anions (RO-) lack this resonance stabilization.
Several structural factors modulate acidity. Electron-withdrawing groups on or near the alpha carbon stabilize the carboxylate anion through inductive effects, increasing acidity. Chloroacetic acid (pKa 2.86) is substantially more acidic than acetic acid (pKa 4.76), and trichloroacetic acid (pKa 0.65) is more acidic still. The inductive effect diminishes with distance from the carboxyl group. Resonance effects also matter: p-nitrobenzoic acid (pKa 3.44) is more acidic than benzoic acid (pKa 4.20), which in turn is more acidic than p-methoxybenzoic acid (pKa 4.47). Hybridization plays a minor role, with vinylic and aryl carboxylic acids being slightly more acidic due to the higher effective electronegativity of sp2 carbons.
Carboxylate salts are named as metal alkanoates (sodium acetate, potassium benzoate) and are fully water-soluble due to their ionic character. Soaps are the sodium or potassium salts of long-chain fatty acids.
<image>Panel A: Resonance structures of the carboxylate anion showing equal distribution of negative charge over two oxygen atoms, with bond lengths marked as equal (1.27 A each). Comparison with an alkoxide anion (localized charge on one oxygen) explains the ~10^11 difference in Ka. Panel B: Bar chart of pKa values for a series of substituted acetic acids: trichloroacetic (0.65), dichloroacetic (1.26), chloroacetic (2.86), fluoroacetic (2.59), acetic (4.76), illustrating the inductive effect of electronegative substituents on acidity.</image>
III. Synthesis of Carboxylic Acids
Oxidation of primary alcohols and aldehydes is a major route to carboxylic acids. Jones reagent (CrO3/H2SO4) and potassium permanganate (KMnO4) oxidize primary alcohols all the way to carboxylic acids and also oxidize aldehydes. Silver oxide (Tollens' reagent) provides a milder, selective method for oxidizing aldehydes to carboxylic acids.
Oxidation of alkylbenzenes with KMnO4 or Na2Cr2O7/H2SO4 converts any benzylic C-H bond to a carboxyl group, giving a benzoic acid derivative regardless of the length of the original alkyl chain. This reaction requires at least one benzylic hydrogen, so tert-butylbenzene does not undergo oxidation.
Carboxylation of Grignard reagents provides an elegant method for extending a carbon chain by one carbon. Treatment of RMgX with carbon dioxide followed by acidic workup gives the carboxylic acid RCOOH. Hydrolysis of nitriles (R-CN) under acidic or basic conditions also yields carboxylic acids, and since nitriles are readily made from alkyl halides by SN2 reaction with NaCN, the overall sequence RX to RCN to RCOOH adds one carbon. Hydrolysis of esters, amides, anhydrides, and acid chlorides all provide carboxylic acids as well. Saponification (base hydrolysis of esters) gives the carboxylate salt. Oxidative cleavage of alkenes through ozonolysis with oxidative workup or through KMnO4 cleavage also generates carboxylic acids.
IV. Reactions of Carboxylic Acids
Carboxylic acids serve as precursors to all the major acid derivatives. Treatment with thionyl chloride (SOCl2) or oxalyl chloride ((COCl)2) converts them to acid chlorides, the most reactive of all carboxylic acid derivatives. Fischer esterification, an acid-catalyzed, reversible reaction with an alcohol, produces esters. The equilibrium can be driven toward the ester by using excess alcohol or by removing water. Amides can be formed by heating the ammonium carboxylate salt of the acid with an amine, although the more practical approach is to first convert the acid to an acid chloride and then react with the amine. Anhydrides are formed by dehydrating two equivalents of the carboxylic acid with a reagent such as P2O5.
Lithium aluminum hydride reduces carboxylic acids to primary alcohols, while sodium borohydride does not have sufficient reducing power for this transformation. Borane-THF complex also reduces carboxylic acids selectively. Decarboxylation, the loss of CO2, occurs readily in beta-keto acids upon heating, proceeding through a six-membered cyclic transition state in which a gamma-hydrogen is transferred to the enol. The initial product is an enol that tautomerizes to the ketone. Malonic acid derivatives also decarboxylate readily, a fact exploited in the malonic ester synthesis. Biological decarboxylations, such as those catalyzed by pyruvate decarboxylase, are enzyme-mediated versions of the same fundamental process.
The Hell-Volhard-Zelinsky reaction introduces a bromine at the alpha position of a carboxylic acid using Br2 and PBr3. The mechanism proceeds through an acyl bromide intermediate that undergoes enolization.
<image>Reaction map centered on a carboxylic acid (RCOOH) with arrows radiating outward to various products. Clockwise from top: acid chloride (SOCl2), ester (ROH/H+), amide (via acid chloride then amine), anhydride (heat or P2O5), primary alcohol (LiAlH4), and decarboxylation product (heat, if beta-keto acid). Each arrow is labeled with the specific reagents. This serves as a comprehensive summary of carboxylic acid reactivity.</image>
V. Spectroscopic Identification
Carboxylic acids have unmistakable IR spectra. The O-H stretch appears as an extremely broad absorption spanning approximately 2500 to 3300 cm-1, often overlapping with the C-H stretching region. The C=O stretch appears as a strong absorption near 1710 to 1725 cm-1. The combination of the characteristically broad O-H absorption and the strong carbonyl peak is virtually diagnostic for the carboxylic acid functional group.
In proton NMR, the carboxylic acid proton resonates very far downfield at delta 10 to 12 ppm and is typically broad and exchangeable with D2O. Alpha hydrogens appear at delta 2.0 to 2.5 ppm. In carbon-13 NMR, the carboxyl carbon appears at delta 170 to 185 ppm. Mass spectrometry commonly shows loss of 17 (OH) or 45 (OC=O) from the molecular ion, and the McLafferty rearrangement is observed when a gamma-hydrogen is present.
<image>Annotated IR spectrum of a carboxylic acid (e.g., propanoic acid) with the characteristic very broad O-H stretch centered around 3000 cm-1 (spanning 2500-3300 cm-1) highlighted and labeled, and the strong sharp C=O stretch at ~1715 cm-1 highlighted and labeled. A comparison with an alcohol IR spectrum is shown as an inset to contrast the O-H stretching patterns.</image>
