Chapter 20 CARBOXYLIC ACIDS

Structure The functional group of a carboxylic acid is a carboxyl group. The general formula for an aliphatic carboxylic acid is RCOOH; that for an aromatic carboxylic acid is ArCOOH. C O H 2 A l t e r n a i v p s o f c b x y g u

Nomenclature - IUPAC IUPAC names: drop the -e from the parent alkane and add the suffix -oic acid. If the compound contains a carbon-carbon double bond, change the infix -an- to -en-.

Nomenclature - IUPAC The carboxyl group takes precedence over most other functional groups.

Nomenclature - IUPAC Dicarboxylic acids: add the suffix -dioic acid to the name of the parent alkane containing both carboxyl groups.

Nomenclature - IUPAC If the carboxyl group is bonded to a ring, name the ring compound and add the suffix -carboxylic acid. The simplest aromatic carboxylic acid is benzoic acid Use numbers to show the location of substituents.

Nomenclature-Common When common names are used, the Greek letters and so forth are often used to locate substituents.

Physical Properties In the liquid and solid states, carboxylic acids are associated by hydrogen bonding into dimeric structures.

Physical Properties Carboxylic acids have significantly higher boiling points than other types of organic compounds of comparable molecular weight. They are polar compounds and form very strong intermolecular hydrogen bonds. Carboxylic acids are more soluble in water than alcohols, ethers, aldehydes, and ketones of comparable molecular weight. They form hydrogen bonds with water molecules through both their C=O and OH groups.

Physical Properties

Physical Properties Water solubility decreases as the relative size of the hydrophobic portion of the molecule increases.

Acidity Carboxylic acids are weak acids. Values of pKa for most aliphatic and aromatic carboxylic acids fall within the range 4 to 5. The greater acidity of carboxylic acids relative to alcohols (both compounds that contain an OH group) is due to resonance stabilization of the carboxylate anion.

Acidity Electron-withdrawing substituents near the carboxyl group increase acidity by their inductive effect.

Acidity The form of a carboxylic acid present at equilibrium in aqueous solution depends on the pH of the solution.

Reaction with Bases Carboxylic acids, whether soluble or insoluble in water, react with NaOH, KOH, and other strong bases to give water-soluble salts. They also form water-soluble salts with ammonia and amines.

Reaction with Bases Carboxylic acids react with sodium bicarbonate and sodium carbonate to form water-soluble salts and carbonic acid. Carbonic acid, in turn, breaks down to carbon dioxide and water.

Reaction with Bases Reaction with bases The acid-base properties of carboxylic acids allow an easy separation of carboxylic acids from water-insoluble nonacidic compounds.

Preparation Carbonation of Grignard reagents Treating a Grignard reagent with carbon dioxide followed by acidification gives a carboxylic acid.

Reduction The carboxyl group is very resistant to reduction. It is not affected by catalytic hydrogenation under conditions that easily reduce aldehydes and ketones to alcohols, and easily reduce alkenes and alkynes to alkanes. Nor is it reduced by NaBH4. Lithium aluminum hydride reduces a carboxyl group to a 1° alcohol. Reduction is carried out in diethyl ether, THF, or other nonreactive, aprotic solvent.

Selective Reduction Carboxyl groups are not affected by catalytic reduction under conditions that reduce aldehydes and ketones. Nor are carboxyl groups reduced by NaBH4.

Fischer Esterification Esters can be prepared by treating a carboxylic acid with an alcohol in the presence of an acid catalyst, commonly H2SO4, ArSO3H, or gaseous HCl. Preparation of an ester in this way is called Fischer esterification.

Fischer Esterification Fischer esterification is an equilibrium reaction. By careful control of experimental conditions, it is possible to prepare esters in high yield. If the alcohol is inexpensive relative to the carboxylic acid, the alcohol can be used in excess to drive the equilibrium to the right. Alternatively, water can be removed by azeotropic distillation and a Dean-Stark trap (Figure 16.1).

Diazomethane Diazomethane, CH2N2 This potentially explosive, toxic, yellow gas is best represented as a hybrid of two contributing structures. Treating a carboxylic acid with diazomethane gives a methyl ester.

Diazomethane Esterification occurs in two steps. Step 1: Take a proton away. Proton transfer to diazomethane gives the methyldiazonium cation. Step 2: Make a bond between a nucleophile and an electrophile. Nucleophilic displacement of N2 gives the ester. + A c a r b o x y l t e n i R C O H N 2 3 : – M h d z u m O C : – R H 3 + N S 2

Acid Chlorides The functional group of an acid halide is a carbonyl group bonded to a halogen atom. Among the acid halides, acid chlorides are by far the most common and the most widely used because of their lower cost and ready availability.

Acid Chlorides Acid chlorides are most often prepared by treating a carboxylic acid with thionyl chloride.

Acid Chlorides The mechanism for this reaction is divided into two steps. Step 1: Reaction with SOCl2 transforms OH, a poor leaving group, into a chlorosulfite group, a good leaving group.

Acid Halides A tetrahedral carbonyl addition intermediate Step 2: Attack of chloride ion gives a tetrahedral carbonyl addition intermediate, which collapses to give the acid chloride. S O C l R - 2 A tetrahedral carbonyl addition intermediate +

Decarboxylation Decarboxylation: The loss of CO2 from a carboxyl group. Most carboxylic acids, if heated to a very high temperature, undergo thermal decarboxylation. Most carboxylic acids, however, are quite resistant to moderate heat and melt or even boil without decarboxylation.

Decarboxylation Exceptions are carboxylic acids that have a carbonyl group beta to the carboxyl group This type of carboxylic acid undergoes decarboxylation readily on mild heating.

Decarboxylation Thermal decarboxylation of a -ketoacid involves rearrangement of six electrons in a cyclic six-membered transition state. Only one carboxyl group in oxalosuccinic acid, an intermediate in the TCA cycle, has a carbonyl group beta to it.

Decarboxylation Decarboxylation occurs if there is any carbonyl group beta to the carboxyl. Malonic acid and substituted malonic acids, for example, also undergo thermal decarboxylation.

Decarboxylation Thermal decarboxylation of malonic acids also involves rearrangement of six electrons in a cyclic six-membered transition state. Step 1: Redistribution of six electrons in a cyclic six-membered transition state gives carbon dioxide and the enol form of a carboxyl group. Step 2: Keto-enol tautomerism of the enol gives the more stable keto form of the carboxyl group. O H C 2 E n o l f a c r b x y i d A s - m e t ( 1 ) +

Problem 17.24 The reaction of an -diketone with concentrated NaOH or KOH gives the salt of an -hydroxycarboxylic acid. This reaction is given the general name benzylic acid rearrangement. Propose a mechanism for this reaction.

Problem 17.24 Step 1: Make a bond between a nucleophile and an electrophile. Addition of hydroxide ion to one of the carbonyl groups forms a tetrahedral carbonyl addition intermediate.

Problem 17.24 Step 2: Collapse of the intermediate with simultaneous regeneration of the carbonyl group and migration of a phenyl group gives benzylic acid.

Problem 17.24 Step 3: Add a proton away and add a proton away, or more simply, transfer a proton to form the benzylate anion.