Carboxylic acids are commonly identified by theirtrivial names. They often have the suffix-ic acid.IUPAC-recommended names also exist; in this system, carboxylic acids have an-oic acid suffix.[2] For example,butyric acid (CH3CH2CH2CO2H) is butanoic acid by IUPAC guidelines. For nomenclature of complex molecules containing a carboxylic acid, the carboxyl can be considered position one of theparent chain even if there are othersubstituents, such as3-chloropropanoic acid. Alternately, it can be named as a "carboxy" or "carboxylic acid" substituent on another parent structure, such as2-carboxyfuran.
The carboxylate anion (R−COO− orR−CO−2) of a carboxylic acid is usually named with the suffix-ate, in keeping with the general pattern of-ic acid and-ate for aconjugate acid and its conjugate base, respectively. For example, the conjugate base ofacetic acid isacetate.
Carbonic acid, which occurs inbicarbonate buffer systems in nature, is not generally classed as one of the carboxylic acids, despite that it has amoiety that looks like a COOH group.
medium to long-chain saturated and unsaturated monocarboxylic acids, with even number of carbons; examples:docosahexaenoic acid andeicosapentaenoic acid (nutritional supplements)
containing at least one aromatic ring; examples:benzoic acid – the sodium salt of benzoic acid is used as a food preservative;salicylic acid – a beta-hydroxy type found in many skin-care products;phenyl alkanoic acids – the class of compounds where a phenyl group is attached to a carboxylic acid
Carboxylic acids arepolar. Because they are both hydrogen-bond acceptors (thecarbonyl−C(=O)−) and hydrogen-bond donors (thehydroxyl−OH), they also participate inhydrogen 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.[3] 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.
Carboxylic acids tend to have higher boiling points than water, because of their greater surface areas and their tendency to form stabilized dimers throughhydrogen bonds. For boiling to occur, either the dimer bonds must be broken or the entire dimer arrangement must be vaporized, increasing theenthalpy of vaporization requirements significantly.
Carboxylic acids are typicallyweak acids, meaning that they only partiallydissociate into[H3O]+cations andR−CO−2anions in neutralaqueous solution. For example, at room temperature, in a 1-molar solution ofacetic acid, only 0.001% of the acid are dissociated (i.e. 10−5 moles out of 1 mol). Electron-withdrawing substituents, such as-CF3 group, give stronger acids (the pKa of acetic acid is 4.76 whereas trifluoroacetic acid, with atrifluoromethyl substituent, has a pKa of 0.23). Electron-donating substituents give weaker acids (the pKa of formic acid is 3.75 whereas acetic acid, with amethyl substituent, has a pKa of 4.76)
Hydrogen oxalate (HO−C(=O)−CO−2) (second dissociation of oxalic acid)
4.14
Deprotonation of carboxylic acids gives carboxylate anions; these areresonance 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.
Carboxylic acids are readily identified as such byinfrared spectroscopy. They exhibit a sharp band associated with vibration of the C=O carbonyl bond (νC=O) between 1680 and 1725 cm−1. A characteristicνO–H band appears as a broad peak in the 2500 to 3000 cm−1 region.[3][6] By1HNMR spectrometry, thehydroxyl hydrogen appears in the 10–13 ppm region, although it is often either broadened or not observed owing to exchange with traces of water.
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 ofaminocarboxylic acids are the main components ofproteins.
In general, industrial routes to carboxylic acids differ from those used on a smaller scale because they require specialized equipment.
Carbonylation of alcohols as illustrated by theCativa process for the production of acetic acid. Formic acid is prepared by a different carbonylation pathway, also starting from methanol.
Oxidation ofaldehydes with air using cobalt and manganese catalysts. The required aldehydes are readily obtained from alkenes byhydroformylation.
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 fromtoluene,terephthalic acid frompara-xylene, andphthalic acid fromortho-xylene are illustrative large-scale conversions.Acrylic acid is generated frompropene.[7]
Carbonylation coupled to the addition of water. This method is effective and versatile for alkenes that generate secondary and tertiarycarbocations, e.g.isobutylene topivalic acid. In theKoch reaction, the addition of water and carbon monoxide toalkenes oralkynes is catalyzed by strong acids. Hydrocarboxylations involve the simultaneous addition of water andCO. Such reactions are sometimes called "Reppe chemistry."
Hydrolysis oftriglycerides obtained from plant or animal oils. These methods of synthesizing some long-chain carboxylic acids are related tosoap making.
Widely practiced reactions convert carboxylic acids intoesters,amides,carboxylate salts,acid chlorides, andalcohols. Their conversion toesters is widely used, e.g. in the production ofpolyesters. Likewise, carboxylic acids are converted intoamides, 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 ofamino acids intopeptides is a significant biochemical process that requiresATP.
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 ammoniumcarboxylate 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.[9] In the presence of a strong acid catalyst, carboxylic acids cancondense 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 formesters via theFischer 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.[9]
TheVilsmaier 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.[10]
The hydroxyl group on carboxylic acids may be replaced with a chlorine atom usingthionyl chloride to giveacyl chlorides. In nature, carboxylic acids are converted tothioesters.Thionyl chloride can be used to convert carboxylic acids to their corresponding acyl chlorides. First, carboxylic acid1 attacks thionyl chloride, and chloride ion leaves. The resultingoxonium ion2 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 intermediate3, a chlorosulfite. The tetrahedral intermediate collapses with the loss ofsulfur dioxide and chloride ion, giving protonated acyl chloride4. Chloride ion can remove the proton on the carbonyl group, giving the acyl chloride5 with a loss ofHCl.
Phosphorus(III) chloride (PCl3) andphosphorus(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, orphosphorus acid, in addition to the desired acid chloride. PCl5 reacts with carboxylic acids in a 1:1 ratio, and producesphosphorus(V) oxychloride (POCl3) and hydrogen chloride (HCl) as byproducts.
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 ageminal 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 ofacetone hydrate from acetone is only 0.002. The carboxylic group is the most acidic in organic compounds.[11]
TheDakin–West reaction converts an amino acid to the corresponding amino ketone.
In theBarbier–Wieland degradation, a carboxylic acid on an aliphatic chain having a simplemethylene bridge at the alpha position can have the chain shortened by one carbon. The inverse procedure is theArndt–Eistert synthesis, where an acid is converted into acyl halide, which is then reacted withdiazomethane to give one additional methylene in the aliphatic chain.
Organolithium reagents (>2 equiv) react with carboxylic acids to give a dilithium 1,1-diolate, a stabletetrahedral intermediate which decomposes to give a ketone upon acidic workup.
TheKolbe electrolysis is an electrolytic, decarboxylative dimerization reaction. It gets rid of the carboxyl groups of two acid molecules, and joins the remaining fragments together.
^Milligan, D. E.; Jacox, M. E. (1971). "Infrared Spectrum and Structure of Intermediates in Reaction of OH with CO".Journal of Chemical Physics.54 (3):927–942.Bibcode:1971JChPh..54..927M.doi:10.1063/1.1675022.
^The value is pKa = −0.2 ± 0.1.Jeevarajan, A. S.; Carmichael, I.; Fessenden, R. W. (1990). "ESR Measurement of the pKa of Carboxyl Radical and Ab Initio Calculation of the Carbon-13 Hyperfine Constant".Journal of Physical Chemistry.94 (4):1372–1376.doi:10.1021/j100367a033.
