Carboxylic acid

Physical properties

Solubility

Carboxylic acids are polar. Because they are both hydrogen-bond acceptors (the carbonyl −C(=O)−) and hydrogen-bond donors (the hydroxyl −OH), they also participate in hydrogen bonding. Together, the hydroxyl and carbonyl group form the functional group carboxyl. Carboxylic acids usually exist as dimers in nonpolar media due to their tendency to "self-associate". Smaller carboxylic acids (1 to 5 carbons) are soluble in water, whereas bigger carboxylic acids have limited solubility due to the increasing hydrophobic nature of the alkyl chain. These longer chain acids tend to be soluble in less-polar solvents such as ethers and alcohols. Aqueous sodium hydroxide and carboxylic acids, even hydrophobic ones, react to yield water-soluble sodium salts. For example, enanthic acid has a low solubility in water (0.2 g/L), but its sodium salt is very soluble in water.

Boiling points

Carboxylic acids tend to have higher boiling points than water, because of their greater surface areas and their tendency to form stabilized dimers through hydrogen bonds. For boiling to occur, either the dimer bonds must be broken or the entire dimer arrangement must be vaporized, increasing the enthalpy of vaporization requirements significantly.

Acidity

Carboxylic acids are Brønsted–Lowry acids because they are proton (H⁺) donors. They are the most common type of organic acid.

Carboxylic acids are typically weak acids, meaning that they only partially dissociate into [H₃O]⁺ cations and R−CO−2 anions in neutral aqueous solution. For example, at room temperature, in a 1-molar solution of acetic acid, only 0.001% of the acid are dissociated (i.e. 10⁻⁵ moles out of 1 mol). Electron-withdrawing substituents such as trifluoromethyl (−CF₃) give stronger acids (the pK_a of acetic acid is 4.76 whereas trifluoroacetic acid, with a trifluoromethyl substituent, has a pK_a of 0.23). Electron-donating substituents give weaker acids (the pK_a of formic acid is 3.75 whereas acetic acid, with a methyl substituent, has a pK_a of 4.76)

Deprotonation of carboxylic acids gives carboxylate anions; these are resonance stabilized, because the negative charge is delocalized over the two oxygen atoms, increasing the stability of the anion. Each of the carbon–oxygen bonds in the carboxylate anion has a partial double-bond character. The carbonyl carbon's partial positive charge is also weakened by the −¹/₂ negative charges on the 2 oxygen atoms.

Odour

Carboxylic acids often have strong sour odours. Esters of carboxylic acids tend to have fruity, pleasant odours, and many are used in perfume.

Characterization

Carboxylic acids are readily identified as such by infrared spectroscopy. They exhibit a sharp band associated with vibration of the C=O carbonyl bond (ν_C=O) between 1680 and 1725 cm⁻¹. A characteristic ν_O–H band appears as a broad peak in the 2500 to 3000 cm⁻¹ region. By ¹H NMR spectrometry, the hydroxyl hydrogen appears in the 10–13 ppm region, although it is often either broadened or not observed owing to exchange with traces of water.

Occurrence and applications

Many carboxylic acids are produced industrially on a large scale. They are also frequently found in nature. Esters of fatty acids are the main components of lipids and polyamides of aminocarboxylic acids are the main components of proteins.

Carboxylic acids are used in the production of polymers, pharmaceuticals, solvents, and food additives. Industrially important carboxylic acids include acetic acid (component of vinegar, precursor to solvents and coatings), acrylic and methacrylic acids (precursors to polymers, adhesives), adipic acid (polymers), citric acid (a flavor and preservative in food and beverages), ethylenediaminetetraacetic acid (chelating agent), fatty acids (coatings), maleic acid (polymers), propionic acid (food preservative), terephthalic acid (polymers). Important carboxylate salts are soaps.

Synthesis

Biological routes

Ribulose-1,5-bisphosphate carboxylase/oxygenase (aka RuBisCo), the most abundant protein, catalyzes the carbonation to give carboxylic acids. This conversion is the carbon-fixation step in photosynthesis. Routes to other biologically prevalent carboxylic acids - citric, oxalic, amino acids, etc. - entail hydrolysis of thioesters and phosphate esters.

Industrial routes

In contrast to methods used on a laboratory scale, industrial routes to carboxylic acids often require specialized equipment for high pressures and high temperatures.

• Carbonylation of alcohols as illustrated by the Cativa process for the production of acetic acid. Formic acid is prepared by a different carbonylation pathway, also starting from methanol.
• Oxidation of aldehydes with air using cobalt and manganese catalysts. The required aldehydes can be obtained from alkenes by hydroformylation.
• Oxidation of hydrocarbons using air. For simple alkanes, this method is inexpensive but not selective enough to be useful. Allylic and benzylic compounds undergo more selective oxidations. Alkyl groups on a benzene ring are oxidized to the carboxylic acid, regardless of its chain length. Benzoic acid from toluene, terephthalic acid from para-xylene, and phthalic acid from ortho-xylene are illustrative large-scale conversions. Acrylic acid is generated from propene.
• Hydrocarboxylation of alkenes. This method is effective for alkenes that generate secondary and tertiary carbocations, e.g. isobutylene to pivalic acid. In the Koch reaction, the addition of water and carbon monoxide to alkenes or alkynes is catalyzed by strong acids. Hydrocarboxylations involve the simultaneous addition of water and CO. Such reactions are sometimes called "Reppe chemistry."

HC≡CH + CO + H₂O → CH₂=CH−CO₂H

• Hydrolysis of esters. Triglycerides, obtained from plant or animal oils, are precursors to long-chain carboxylic acids are related to soap making.
• Fermentation of ethanol. This method is used in the production of vinegar.
• Carbonation, such as the Kolbe–Schmitt reaction as a route to salicylic acid, precursor to aspirin.

Laboratory methods

Preparative methods for small scale reactions for research or for production of fine chemicals often employ expensive consumable reagents.

• Oxidation of primary alcohols or aldehydes with strong oxidants such as potassium dichromate, Jones reagent, potassium permanganate, or sodium chlorite. The method is more suitable for laboratory conditions than the industrial use of air, which is "greener" because it yields less inorganic side products such as chromium or manganese oxides.
• Oxidative cleavage of olefins by ozonolysis, potassium permanganate, or potassium dichromate.
• Hydrolysis of nitriles, esters, or amides, usually with acid- or base-catalysis.
• Carbonation of a Grignard reagent and organolithium reagents:

RLi + CO₂ → RCO−2Li⁺

RCO−2Li⁺ + HCl → RCO₂H + LiCl

• Halogenation followed by hydrolysis of methyl ketones in the haloform reaction
• Base-catalyzed cleavage of non-enolizable ketones, especially aryl ketones:

R−C(=O)−Ar + H₂O → R−CO₂H + ArH

Less-common reactions

Many reactions produce carboxylic acids but are used only in specific cases or are mainly of academic interest.

• Disproportionation of an aldehyde in the Cannizzaro reaction
• Rearrangement of diketones in the benzilic acid rearrangement
• Involving the generation of benzoic acids are the von Richter reaction from nitrobenzenes and the Kolbe–Schmitt reaction from phenols.

Reactions

Acid-base reactions

Carboxylic acids react with bases to form carboxylate salts, in which the hydrogen of the hydroxyl (–OH) group is replaced with a metal cation. For example, acetic acid found in vinegar reacts with sodium bicarbonate (baking soda) to form sodium acetate, carbon dioxide, and water:

CH₃COOH + NaHCO₃ → CH₃COO⁻Na⁺ + CO₂ + H₂O

Conversion to esters, amides, anhydrides

Widely practiced reactions convert carboxylic acids into esters, amides, carboxylate salts, acid chlorides, acid anhydrides, and alcohols. Their conversion to esters is widely used, e.g. in the production of polyesters. Likewise, carboxylic acids are converted into amides, but this conversion typically does not occur by direct reaction of the carboxylic acid and the amine. Instead esters are typical precursors to amides. The conversion of amino acids into peptides is a significant biochemical process that requires ATP.

Converting a carboxylic acid to an amide is possible, but not straightforward. Instead of acting as a nucleophile, an amine will react as a base in the presence of a carboxylic acid to give the ammonium carboxylate salt. Heating the salt to above 100 °C will drive off water and lead to the formation of the amide. This method of synthesizing amides is industrially important, and has laboratory applications as well.

In the presence of a strong acid catalyst, carboxylic acids can condense to form acid anhydrides. The condensation produces water, however, which can hydrolyze the anhydride back to the starting carboxylic acids. Thus, the formation of the anhydride via condensation is an equilibrium process.

Under acid-catalyzed conditions, carboxylic acids will react with alcohols to form esters via the Fischer esterification reaction, which is also an equilibrium process. Alternatively, diazomethane can be used to convert an acid to an ester. While esterification reactions with diazomethane often give quantitative yields, diazomethane is only useful for forming methyl esters.

Reduction

Like esters, most carboxylic acids can be reduced to alcohols by hydrogenation, or using hydride transferring agents such as lithium aluminium hydride. Strong alkyl transferring agents, such as organolithium compounds but not Grignard reagents, will reduce carboxylic acids to ketones along with transfer of the alkyl group.

The Vilsmaier reagent (N,N-Dimethyl(chloromethylene)ammonium chloride; [ClHC=N⁺(CH₃)₂]Cl⁻) is a highly chemoselective agent for carboxylic acid reduction. It selectively activates the carboxylic acid to give the carboxymethyleneammonium salt, which can be reduced by a mild reductant like lithium tris(t-butoxy)aluminum hydride to afford an aldehyde in a one pot procedure. This procedure is known to tolerate reactive carbonyl functionalities such as ketone as well as moderately reactive ester, olefin, nitrile, and halide moieties.

Conversion to acyl halides

The hydroxyl group on carboxylic acids may be replaced with a chlorine atom using thionyl chloride to give acyl chlorides. In nature, carboxylic acids are converted to thioesters. Thionyl chloride can be used to convert carboxylic acids to their corresponding acyl chlorides. First, carboxylic acid 1 attacks thionyl chloride, and chloride ion leaves. The resulting oxonium ion 2 is activated towards nucleophilic attack and has a good leaving group, setting it apart from a normal carboxylic acid. In the next step, 2 is attacked by chloride ion to give tetrahedral intermediate 3, a chlorosulfite. The tetrahedral intermediate collapses with the loss of sulfur dioxide and chloride ion, giving protonated acyl chloride 4. Chloride ion can remove the proton on the carbonyl group, giving the acyl chloride 5 with a loss of HCl.

Phosphorus(III) chloride (PCl₃) and phosphorus(V) chloride (PCl₅) will also convert carboxylic acids to acid chlorides, by a similar mechanism. One equivalent of PCl₃ can react with three equivalents of acid, producing one equivalent of H₃PO₃, or phosphorus acid, in addition to the desired acid chloride. PCl₅ reacts with carboxylic acids in a 1:1 ratio, and produces phosphorus(V) oxychloride (POCl₃) and hydrogen chloride (HCl) as byproducts.

Reactions with carbanion equivalents

Carboxylic acids react with Grignard reagents and organolithiums to form ketones. The first equivalent of nucleophile acts as a base and deprotonates the acid. A second equivalent will attack the carbonyl group to create a geminal alkoxide dianion, which is protonated upon workup to give the hydrate of a ketone. Because most ketone hydrates are unstable relative to their corresponding ketones, the equilibrium between the two is shifted heavily in favor of the ketone. For example, the equilibrium constant for the formation of acetone hydrate from acetone is only 0.002. The carboxylic group is the most acidic in organic compounds.

Specialized reactions

• As with all carbonyl compounds, the protons on the α-carbon are labile due to keto–enol tautomerization. Thus, the α-carbon is easily halogenated in the Hell–Volhard–Zelinsky halogenation.
• The Schmidt reaction converts carboxylic acids to amines.
• Carboxylic acids are decarboxylated in the Hunsdiecker reaction.
• The Dakin–West reaction converts an amino acid to the corresponding amino ketone.
• In the Barbier–Wieland degradation, a carboxylic acid on an aliphatic chain having a simple methylene bridge at the alpha position can have the chain shortened by one carbon. The inverse procedure is the Arndt–Eistert synthesis, where an acid is converted into acyl halide, which is then reacted with diazomethane to give one additional methylene in the aliphatic chain.
• Many acids undergo oxidative decarboxylation. Enzymes that catalyze these reactions are known as carboxylases (EC 6.4.1) and decarboxylases (EC 4.1.1).
• Carboxylic acids are reduced to aldehydes via the ester and DIBAL, via the acid chloride in the Rosenmund reduction and via the thioester in the Fukuyama reduction.
• In ketonic decarboxylation carboxylic acids are converted to ketones.
• Organolithium reagents (>2 equiv) react with carboxylic acids to give a dilithium 1,1-diolate, a stable tetrahedral intermediate which decomposes to give a ketone upon acidic workup.
• The Kolbe electrolysis is an electrolytic, decarboxylative dimerization reaction. It gets rid of the carboxyl groups of two acid molecules, and joins the remaining fragments together.

Carboxyl radical

The carboxyl radical, •COOH, only exists briefly. The acid dissociation constant of •COOH has been measured using electron paramagnetic resonance spectroscopy. The carboxyl group tends to dimerise to form oxalic acid.