Acidity Basicity of Carboxylic Acids Acidity of Carboxylic Acids Salt Formation Carboxylic acids are relatively strong acids Carboxylic acids have much lower pKa values than do alcohols The lowered pKa values are due to the electron withdrawing effect of the positively polarized carbonyl carbon and the resonance stabilization of the carboxylate group Two of the three resonance forms of the carboxylate ion are equivalent leading to a symmetrical ion with equal carbon oxygen bond lengths 1 26 midway between a carbon oxygen double bond 1 20 and a carbon oxygen single bond 1 34 Electron withdrawing substituents increase the acidity of carboxylic acids The inductive effect of electron withdrawing groups close to the carboxy group causes an increase in acidity Three electron withdrawing groups on the carbon sometimes results in acidity near that of some inorganic acids The dioic acids have two pKa values In ethanedioic and propanedioic acids the first pKa is lowered by the electron withdrawing effect of the second In higher dioic acids both pKa values are close to monocarboxylic acids Carboxylate salts of carboxylic acids can be prepared by treatment of the acid with a base such as NaOH Na2CO3 or NaHCO3 These salts are much more water soluble than the corresponding acids Carboxylate salts are named by specifying the metal and then replacing ic acid with ate Acidity Basicity of Carboxylic Acids Basicity of Carboxylic Acids Carboxylic acids may be protonated on the carbonyl oxygen The carbonyl oxygen of a carboxylic acid may be protonated by strong acids to give alkyloxonium ions The carbonyl oxygen is more basic than the OH group of alcohols due to resonance stabilization of the alkyloxonium ion Note the protonation reaction is not particularly strong Preparation of Carboxylic Acids Industrial Synthesis of Carboxylic Acids Formic acid and acetic acid are manufactured on a large scale industrially Formic Acid Synthesis Acetic Acid Synthesis Via Oxidation of Ethene Wacker Process O Via Carbonylation of Methanol Monsanto Process Other important industrial carboxylic acids include the two dicarboxylic acids Hexanedioic acid 1 4 benzenedicarboxylic acid Nylon Plastics Preparation of Carboxylic Acids Oxidation of primary alcohols and of aldehydes furnishes carboxylic acids Primary alcohols oxidize first to aldehydes which then may further oxidize to carboxylic acids Oxidation of Primary Alcohols Oxidation of Aldehydes Oxidants include CrO2 KMnO4 and HNO3 Nitric acid is often chosen as the oxidant because it is one of the cheapest strong oxidants Preparation of Carboxylic Acids Carbonation of Organometallic Reagents Organometallic reagents react with carbon dioxide to give carboxylic acids Carbonation or reaction of an organometallic reagent with CO2 dry ice produces a carboxylate salt which yields a carboxylic acid upon protonation in aqueous acid A two step synthesis allows the conversion of an alkyl halide into the corresponding carboxylic acid having one more carbon Preparation of Carboxylic Acids Hydrolysis of Nitriles Nitriles hydrolyze to carboxylic acids A second method for preparing a carboxylic acid with an additional carbon is through the synthesis and hydrolysis of a nitrile RC N Nitrile hydrolysis is preferable to Grignard carbonation when the substrate contains other functional groups capable of reacting with the Grignard reagent hydroxy carbonyl nitro Reactions of Carboxylic Acids Nucleophilic Attack at the Carbonyl Group The carbonyl carbon is attacked by nucleophiles Carboxylic acids and their derivatives of the form RCOL L leaving group can be attacked by nucleophiles Unlike the reactions with aldehydes and ketones the attacking nucleophile displaces the leaving group resulting in an addition elimination reaction An addition elimination reaction proceeds through a tetrahedral intermediate Addition elimination is catalyzed by acid or base Substitution at the carboxy carbon the addition elimination mechanism Base catalyzed addition elimination Base catalysis proceeds by deprotonating the nucleophile MECHANISM Acid catalyzed addition elimination Acid catalysis proceeds by initial protonation of the carbonyl group and subsequent protonation of the leaving group MECHANISM Substitution in carboxylic acids is inhibited by a poor leaving group and the acidic proton Two problems can be encountered when trying to convert a carboxylic acid into one of its derivatives by the addition elimination process 1 Hydroxide ion is a poor leaving group 2 Carboxylic proton is acidic and most nucleophiles are bases An alternate acid base reaction may occur With less basic nucleophiles especially under acidic conditions substitution through the addition elimination mechanism may occur In the esterification of a carboxylic acid an alcohol and a carboxylic acid react in the presence of acid to form an ester and water The acid serves to protonate both the carbonyl oxygen activating the carbonyl towards nucleophilic addition and the carboxy OH converting it into a better leaving group Derivatives of Carboxylic Acids Acyl Halides Acyl Chlorides Acyl Bromides Alkanoyl acyl halides are formed by using inorganic derivatives of carboxylic acids Alkanoyl acyl halides can be prepared from carboxylic acids by using reagents such as SOCl2 or PBr3 The reaction with either reagent begins with the conversion of the poor leaving group OH into a good leaving group MECHANISM Acyl Chloride Formation Acids combine with alkanoyl halides to produce anhydrides An alkanoyl halide is activated to attack by weaker nucleophiles by the electronegative power of its halogen atom Derivatives of Carboxylic Acids Carboxylic Anhydrides Cyclic Anhydrides Treatment of alkanoyl halides with carboxylic acids leads to carboxylic anhydrides 5 or 6 membered cyclic anhydrides can be prepared by simple heating of the corresponding dicarboxylic acids Because the halogen in an alkanoyl halide and the RCO2 group in an anhydride are good leaving groups alkanoyl halides and anhydrides are often useful intermediates during the preparation of other compounds Derivatives of Carboxylic Acids Esters Cyclic Esters Lactones Carboxylic acids react with alcohols to form esters Esters can be formed in an equilibrium process by combining a carboxylic acid and an alcohol in the presence of catalytic amounts of a mineral acid H is usually close to 0 for an esterification reaction Since S is also close to zero G will be close to zero and the equilibrium