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12 Introduction to Organic Chemistry 2 ed William H. Brown 12-1 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 12 Carboxylic Acids Chapter 12 12-2 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 12 Structure • The functional group of a carboxylic acid is a carboxyl group •• •• O C COOH •• O •• CO2 H H • The general formula of an aliphatic carboxylic acid is RCO2H; that of an aromatic carboxylic acid is ArCO2H 12-3 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 12 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- C6 H5 CH2 = CHCO2 H Propenoic acid (Acrylic acid) H C C H CO2 H trans -3-Phenylpropenoic acid (Cinnamic acid) 12-4 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 12 Nomenclature - IUPAC • the carboxyl group takes precedence over most other functional groups OH CH3 CHCH 2 CH2 CH2 CO 2 H 5-Hydroxyhexanoic acid O H2 NCH2 CH 2 CH2 CO 2 H CH3 CCH2 CH 2 CH2 CO 2 H 4-Aminobutanoic acid 5-Oxohexanoic acid 12-5 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 12 Nomenclature - IUPAC • Dicarboxylic acids: add the suffix -dioic acid to the name of the parent alkane containing both carboxyl groups O O HOC-COH Ethanedioic acid (Oxalic acid) O O HOCCH2 COH Propanedioic acid (Malonic acid) O O HOCCH2 CH2 COH Butanedioic acid (Succinic acid) 12-6 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 12 Nomenclature - IUPAC • If the carboxyl group is attached to a ring, name the ring compound and add the suffix -carboxylic acid 2 3 1 CO2 H 2-Cyclohexenecarboxylic acid HO2 C CO2 H trans-1,3-Cyclopentanedicarboxylic acid 12-7 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 12 Nomenclature - IUPAC • The simplest aromatic carboxylic acid is benzoic acid • derivatives are named using numbers to show the location of substituents relative to the carboxyl group CO 2 H CO 2 H 1 OH 2 Benzoic acid 2-Hydroxybenzoic acid (Salicylic acid) 3 H2 N 4 2 1 CO 2 H 4-Aminobenzoic acid 12-8 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 12 Nomenclature - IUPAC • Aromatic dicarboxylic acids are named by adding the words “dicarboxylic acid” to “benzene” CO 2 H HO 2 C CO 2 H CO 2 H 1,4-Benzenedicarboxylic acid 1,2-Benzenedicarboxylic acid (Terephthalic acid) (Phthalic acid) 12-9 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 12 Nomenclature-Common • When common names are used, the letters a, b, g, d, etc. are often used to locate substituents d g b a O C-C- C-C-C- OH 5 4 3 2 1 N H2 HOCH2 CH 2 CH2 CO 2 H 4-Hydroxybutanoic acid (g-Hydroxybutyric acid) CH3 CHCO 2 H 2-Aminopropanoic acid (a-Aminopropionic acid; Alanine) 12-10 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 12 Physical Properties • In the liquid and solid states, carboxylic acids are associated by hydrogen bonding into dimeric structures 12-11 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 12 Physical Properties • Carboxylic acids are polar compounds and form very strong intermolecular hydrogen bonds through both their C=O and OH groups • they have significantly higher boiling points than other types of organic compounds of comparable molecular weight • they are more soluble in water than alcohols, ethers, aldehydes, and ketones of comparable molecular weight 12-12 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 12 Physical Properties • Water solubility decreases as the relative size of the hydrophobic portion of the molecule increases 12-13 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 12 Acidity • Carboxylic acids are weak acids • values of pKa for most aliphatic and aromatic carboxylic acids fall within the range 4 - 5 CH3 CO 2 H + H2 O Ka = CH3 CO 2 - + H3 O + [CH 3 CO 2 - ] [H 3 O + ] [CH 3 CO 2 H] = 1.74 x 10-5 pK a = 4.76 12-14 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 12 Acidity • The greater acidity of carboxylic acids relative to alcohols is due to two factors: • the significant resonance stabilization of a carboxylate anion compared with an alkoxide anion O CH3 O C CH3 O - - CH3 CH2 O - C O these equivalent contributing structures delocalize the negative charge and stabilize the carboxylic anion the negative charge is localized on oxygen 12-15 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 12 Acidity • the electron-withdrawing inductive effect of the adjacent carbonyl group on the O-H bond dO CH3 C d+ O-H because electron density is withdrawn from the O-H bond, the carboxyl hydrogen is lost more easily to a base 12-16 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 12 Acidity • electron-withdrawing substituents near the carboxyl group increase acidity through their inductive effect H Br I Cl F CH2 CO2 H CH2 CO2 H CH2 CO2 H CH2 CO2 H CH2 CO2 H 3.18 4.76 2.90 2.86 2.59 Increasing acid strength 12-17 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 12 Acidity • multiple substitution of electron-withdrawing groups further increases acidity CH3 CO2 H ClCH 2 CO2 H Cl 2 CHCO2 H Cl 3 CCO2 H Acetic Chloroacetic Dichloroacetic Trichloroacetic acid acid acid acid pKa : 4.76 2.86 1.48 0.70 Increasing acid strength 12-18 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 12 Acidity • The inductive effect of an electron-withdrawing substituent falls off rapidly with its distance from the carboxyl group Cl Cl Cl CH2 CH2 CH2 CO2 H CH3 CHCH2 CO2 H CH3 CH2 CHCO2 H 4-Chlorobutanoic 3-Chlorobutanoic 2-Chlorobutanoic acid acid acid pKa : 3.98 2.83 4.52 Increasing acid strength 12-19 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 12 Reaction with Bases • Carboxylic acids, whether soluble or insoluble in water, react with NaOH, KOH, and other strong bases to give water-soluble salts CO2 H + NaOH Benzoic acid (slightly soluble in water) H2 O - CO2 Na + + H2 O Sodium benzoate (60 g/100 mL water) 12-20 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 12 Reaction with Bases • they also form water-soluble salts with ammonia and amines CO2 H + NH3 Benzoic acid (slightly soluble in water) - H2 O CO2 NH 4 + Ammonium benzoate (20 g/100 mL water) 12-21 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 12 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 H2 O CH3 CO2 H + Na HCO3 - CH3 CO2 Na + + CO2 + H2 O 12-22 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 12 Reduction • The carboxyl group is one of the organic functional groups most resistant to reduction • it is not affected by catalytic hydrogenation under conditions that easily reduce aldehydes and ketones to alcohols, and reduce alkenes and alkynes to alkanes • it is not reduced by NaBH4, a reagent that readily reduces the carbonyl groups of aldehydes and ketones 12-23 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 12 Reduction by LiAlH4 • Lithium aluminum hydride reduces a carboxyl group to a 1° alcohol • reduction is most commonly carried out in diethyl ether or THF O COH 1 . LiAlH 4 , ether 2. H 2O 3-Cyclopentenecarboxylic acid CH2 OH + LiOH + Al(OH) 3 4-Hydroxymethylcyclopentene 12-24 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 12 Selective Reduction • The carboxyl group is not affected by catalytic hydrogenation under conditions that easily reduce aldehydes and ketones to alcohols. O O CH3 CCH2 CH2 CH2 COH 5-Oxohexanoic acid Pt 25° C, 2 atm OH O CH3 CHCH2 CH2 CH2 COH 5-Hydroxyhexanoic acid 12-25 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 12 Selective Reduction • it is also possible to selectively reduce the carbonyl group of an aldehyde or ketone using the less reactive NaBH4 O O CCH2 CH2 CH2 COH 5-Oxo-5-phenylpentanoic acid 1 . NaBH 4 2.H 2O OH O CHCH2 CH2 CH2 COH 5-Hydroxy-5-phenylpentanoic acid 12-26 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 12 Fischer Esterification • Esters can be prepared by treatment of a carboxylic acid with an alcohol in the presence of an acid catalyst, most commonly H2SO4 or gaseous HCl O H2 SO 4 CH3 COH + CH3 CH2 OH Ethanoic acid Ethanol (Acetic acid) (Ethyl alcohol) O CH3 COCH2 CH3 + H2 O Ethyl ethanoate (Ethyl acetate) 12-27 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 12 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, it can be used in excess to drive the equilibrium to the right • if water can be removed from the reaction mixture, the equilibrium is also driven to the right 12-28 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 12 Fischer Esterification • A key intermediate in Fischer esterification is the tetrahedral carbonyl addition intermediate formed by addition of ROH to the C=O group tetrahedral carbonyl addition intermediate •• •• H O •• C ••OCH3 H •• •• R •• C ••OH + HOCH 3 •• R •• R •• H+ •• •• •• H O + O O •• •• C OCH 3 + HOH •• •• 12-29 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 12 Decarboxylation • Decarboxylation: 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 12-30 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 12 Decarboxylation • Exceptions are carboxylic acids that have a carbonyl group beta to the carboxyl group • this type of carboxylic acid undergoes decarboxylation on mild heating O O b a warm CH3 - C- CH2 - C- OH 3-Oxobutanoic acid (Acetoacetic acid) O CH3 - C- CH3 + CO2 Acetone 12-31 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 12 Decarboxylation • thermal decarboxylation of a b-ketoacid involves rearrangement of six electrons in a cyclic sixmembered transition state O H3 C C H C O O C C O H H (A cyclic six-membered transition state) H3 C H C H O C H O enol of a ketone O CH3 - C- CH3 + CO2 12-32 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 12 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 O O O 140-150°C CH3 COH + CO2 HOCCH2 COH Propanedioic acid (Malonic acid) 12-33 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 12 Decarboxylation • thermal decarboxylation of malonic acids also involves rearrangement of six electrons in a cyclic sixmembered transition state H H O O O O C C C C HO HO C O C O H H H H enol of a A cyclic six-membered carboxylic acid transition state O CH3 -C-OH + CO2 12-34 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 12 Carboxylic Acids End Chapter 12 12-35 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.