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17 Organic Chemistry William H. Brown & Christopher S. Foote 17-1 17 Carboxylic Acids Chapter 17 17-2 17 Structure The functional group of a carboxylic acid is a carboxyl group : O: : C :O COOH CO 2 H H • the general formula of an aliphatic carboxylic acid is RCOOH; that of an aromatic carboxylic acid is ArCOOH 17-3 17 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 -enCOOH COOH COOH C6 H5 Propenoic acid (Acrylic acid) trans-2-Butenoic acid (Crotonic acid) trans-3-Phenylpropenoic acid (Cinnamic acid) 17-4 17 Nomenclature - IUPAC The carboxyl group takes precedence over most other functional groups OH COOH (R)-5-Hydroxyhexanoic acid O COOH 5-Oxohexanoic acid H2N COOH 4-Aminobutanoic acid 17-5 17 Nomenclature - IUPAC • dicarboxylic acids: add the suffix -dioic acid to the name of the parent alkane containing both carboxyl groups O HO O OH O Ethanedioic acid (Oxalic acid) O HO O OH O Butanedioic acid (Succinic acid) HO O HO OH Propanedioic acid (Malonic acid) O O OH Pentanedioic acid (Glutaric acid) HO OH O Hexanedioic acid (Adipic acid) 17-6 17 Nomenclature - IUPAC • if the carboxyl group is attached to a ring, name the ring compound and add the suffix -carboxylic acid 2 3 1 COOH 2-Cyclohexenecarboxylic acid H OOC COOH trans-1,3-Cyclopentanedicarboxylic acid 17-7 17 Nomenclature - IUPAC • benzoic acid is the simplest aromatic carboxylic acid • use numbers to show the location of substituents COOH COOH COOH OH COOH COOH COOH Benzoic 2-Hydroxybenzoic 1,2-Benzene1,4-Benzeneacid acid dicarboxylic acid dicarboxylic acid (Salicylic acid) (Phthalic acid) (Terephthalic acid) 17-8 17 Nomenclature-Common • when common names are used, the letters etc. are often used to locate substituents O 5 1 OH 4 3 2 O H2 N O OH 4-Aminobutanoic acid (-Aminobutyric acid; GABA) OH NH2 2-Aminopropanoic acid (-Aminopropionic acid; alanine) 17-9 17 Physical Properties In the liquid and solid states, carboxylic acids are associated by hydrogen bonding into dimeric structures - + + - 17-10 17 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 their C=O and OH groups 17-11 17 Physical Properties • water solubility decreases as the relative size of the hydrophobic portion of the molecule increases hydrophilic region hydrophobic region 17-12 17 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 containing an OH group is due to resonance stabilization of the carboxylate anion 17-13 17 Acidity • electron-withdrawing substituents near the carboxyl group increase acidity through their inductive effect CH3 COOH ClCH 2 COOH Cl 2 CHCOOH Acetic Chloroacetic Dichloroacetic acid acid acid pKa: 4.76 2.86 1.48 Increasing acid strength Cl 3 CCOOH Trichloroacetic acid 0.70 17-14 17 Reaction with Bases Carboxylic acids, whether soluble or insoluble in water, react with NaOH, KOH, and other strong bases to give water-soluble salts COOH + NaOH - H2 O Benzoic acid (slightly soluble in water) COO Na + + H2 O Sodium benzoate (60 g/100 mL water) They also form water-soluble salts with ammonia and amines COOH + NH3 Benzoic acid (slightly soluble in water) - H2 O COO NH4 + Ammonium benzoate (20 g/100 mL water) 17-15 17 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 CH3 COOH + NaHCO 3 + CH3 COO Na + CO 2 + H2 O 17-16 17 Reaction with Bases QuickTime™ and a Photo - JPEG decompressor are needed to see this picture. 17-17 17 Preparation Carbonation of Grignard reagents • treatment of a Grignard reagent with carbon dioxide followed by acidification gives a carboxylic acid O Mg Br + C O Carbon dioxide O C-O - [ Mg Br ] + HCl H2 O O C-OH + Mg 2 + Cyclopentanecarboxylic acid 17-18 17 Methanol to Acetic Acid Acetic acid is synthesized by carbonylation of methanol • the carbonylation is exothermic O CH3 OH + CO CH3 COH H° = -138 kJ(33 kcal)/mol • the Monsanto process uses a soluble rhodium(III) salt and HI to catalyze the reaction 17-19 17 Methanol to Acetic Acid • Steps 1 and 2: preparation of the catalyst: CH3 OH + HI CH3 I + H2 O CH3 I + Rh( CO) I 2 [ CH3 - Rh( CO) I 3 ] An methyl-rhodium carbonyl complex • Steps 3 and 4: the catalytic cycle O CH3 COH [ CH3 - Rh( CO) I 3 ] - (4) CH3 OH catalytic cycle O [ CH3 C- Rh( CO) I 3 ] An acyl-rhodium carbonyl complex CO (3) 17-20 17 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 reduce alkenes and alkynes to alkanes • it is not reduced by NaBH4 17-21 17 Reduction by LiAlH4 Lithium aluminum hydride reduces a carboxyl group to a 1° alcohol • reduction is carried out in diethyl ether, THF, or other nonreactive, aprotic solvent O COH 1 . LiAlH4 , ether 2 . H2 O CH2 OH + LiOH + Al(OH) 3 4-Hydroxymethylcyclopentene 17-22 17 Selective Reduction • carboxyl groups are not affected by catalytic reduction under conditions that reduce aldehydes and ketones O O OH + 5-Oxohexanoic acid H2 Pt 25°C, 2 atm OH O OH 5-Hydroxyhexanoic acid 17-23 17 Selective Reduction • using the less reactive NaBH4, it is possible to reduce the carbonyl group of an aldehyde or ketone without affecting a carboxyl group O C6 H5 O OH OH 5-Oxo-5-phenylpentanoic acid 1 . Na BH 4 2 . H2 O C6 H5 O OH 5-Hydroxy-5-phenyl pentanoic acid 17-24 17 Fischer Esterification Esters can be prepared by treatment of a carboxylic acid with an alcohol in the presence of an acid catalyst, commonly H2SO4 or gaseous HCl O OH Ethanoic acid (Acetic acid) H2 SO 4 + HO Ethanol (Ethyl alcohol) O + H2 O O Ethyl ethanoate (Ethyl acetate) 17-25 17 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 • alternatively, water can be removed by azeotropic distillation and a Dean-Stark trap 17-26 17 Fischer Esterification • a key intermediate in Fischer esterification is the tetrahedral carbonyl addition intermediate formed by addition of ROH to the C=O group O O TCAI H R C OCH3 O H + + H H R C OH + HOCH3 O R C OCH3 + HOH 17-27 17 Diazomethane Diazomethane, CH2N2 • a potentially explosive, toxic yellow gas, is best drawn as a hybrid of two contributing structures H C N N: : : + + H C N N: H H • treatment of a carboxylic acid with diazomethane gives a methyl ester O RCOH + ether CH2 N 2 Diazomethane O RCOCH3 + N 2 A methyl ester 17-28 17 Diazomethane Esterification occurs in two steps Step 1: proton transfer to diazomethane O + + : R C O H CH2 N N O + – + R C O: CH3 -N N A carboxylate Methylanion diazonium cation Step 2: nucleophilic displacement of N2 O + - + R- C-O: CH3 -N N SN 2 O R- C-O- CH 3 + :N N 17-29 17 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 O - C- X O CH3 CCl Functional group of an acid halide Acetyl chloride O C-Cl Benzoyl chloride 17-30 17 Acid Chlorides • acid chlorides are most often prepared by treatment of a carboxylic acid with thionyl chloride O OH + SOCl 2 Butanoic Thionyl acid chloride O Cl + SO 2 + HCl Butanoyl chloride 17-31 17 Acid Chlorides The mechanism for this reaction is divided into two steps. Step 1: OH-, a poor leaving group, is transformed into a chlorosulfite group, a good leaving group O O R- C-O- H + Cl-S- Cl O O R C O S Cl + H- Cl A chlorosulfite group 17-32 17 Acid Halides Step 2: attack of chloride ion gives a tetrahedral carbonyl addition intermediate, which collapses to give the acid chloride O O R C O S Cl + :Cl :O - - O R C O S Cl O R- C-Cl + SO 2 + :Cl - Cl A tetrahedral carbonyl addition intermediate 17-33 17 Decarboxylation Decarboxylation: loss of CO2 from a carboxyl group • most carboxylic acids, if heated to a very high temperature, undergo thermal decarboxylation O RCOH decarboxylation heat RH + CO 2 • most carboxylic acids, however, are quite resistant to moderate heat and melt or even boil without decarboxylation 17-34 17 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 warm OH 3-Oxobutanoic acid (Acetoacetic acid) O + CO 2 Acetone 17-35 17 Decarboxylation • thermal decarboxylation of a -ketoacid involves rearrangement of six electrons in a cyclic sixmembered transition state enol of a ketone O H O (1) O O H O C (2) O O + CO 2 (A cyclic six-membered transition state) 17-36 17 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 140-150°C HOCCH2 COH Propanedioic acid (Malonic acid) O CH3 COH + CO 2 17-37 17 Decarboxylation • thermal decarboxylation of malonic acids also involves rearrangement of six electrons in a cyclic sixmembered transition state O HO H O O (1) O A cyclic six-membered transition state HO H O C O (2) O + HO CO 2 Enol of a carboxylic acid 17-38 17 Prob 17.17 Each compound shows strong absorption between 1720 and 1700 cm-1, and strong broad absorption over the region 2500-3500 cm-1. Propose a structural formula for each compound. (a) C5 H1 0 O 2 1 13 H-NMR C-NMR 0.94 (t, 3H) 180.71 1.39 (m, 2H) 33.89 1.62 (m, 2H) 26.76 2.35 (t, 2H) 22.21 13.69 12.0 (s 1H) (b) C6 H1 2 O 2 1 H-NMR 13 C-NMR 1.08 (s, 9H) 179.29 2.23 (s, 2H) 47.82 12.1 (s, 1H) 30.62 29.57 17-39 17 Prob 17.17 (cont’d) (d) C5 H8 O4 (c) C5 H8 O4 1 13 H-NMR C-NMR 0.93 (t, 3H) 170.94 1.80 (m, 2H) 53.28 3.10 (t, 1H) 21.90 12.7 (s, 2H) 1 13 C-NMR H-NMR 1.29 (s, 6H) 174.01 12.8 (s, 2H) 48.77 22.56 11.81 (e) C4 H6 O2 1 H-NMR 13 C-NMR 1.91 (d, 3H) 172.26 5.86 (d, 1H) 147.53 7.10 (m, 1H) 122.24 12.4 (s, 1H) 18.11 (f) C3 H4 Cl 2 O2 1 H-NMR 13 C-NMR 2.34 (s, 3H) 171.82 11.3 (s, 1H) 79.36 34.02 17-40 17 Prob 17.17 (cont’d) (g) C5 H8 Cl 2 O2 1 13 H-NMR C-NMR 1.42 (s, 6H) 180.15 6.10 (s, 1H) 77.78 12.4 (s, 1H) 51.88 20.71 (h) C5 H9 Br O 2 1 H-NMR 13 C-NMR 0.97 (t, 3H) 176.36 1.50 (m, 2H) 45.08 2.05 (m, 2H) 36.49 20.48 4.25 (t, 1H) 13.24 12.1 (s 1H) (i) C4 H8 O3 1 13 H-NMR C-NMR 2.62 (t, 2H) 177.33 3.38 (s, 3H) 67.55 3.68 (s, 2H) 58.72 11.5 (s, 1H) 34.75 17-41 17 Prob 17.18 Complete these reactions. (a) CH2 OH CHO 1 . Ag ( N H3 ) 2 (b) HO OH O (c) + 2 . H2 O, HCl 1 . Cl 2 , KOH in water/dioxane 2 . HCl, H2 O Br (d) K2 Cr 2 O 7 , H2 SO4 H2 O, acetone 1 . Mg, e t he r 2 . CO 2 3 . HCl, H2 O OCH3 17-42 17 Prob 17.19 Show how to bring about each conversion. O O (a) OH COOH Cl (b) OH O CH2 OH COOH (c) (d) C6 H5 OH C6 H5 COOH 17-43 17 Prob 17.21 Draw a structural formula for each starting compound. O (a) C6 H1 4 O (b) C6 H1 2 O (c) C6 H1 4 O 2 oxidation OH O oxidation oxidation OH O HO OH O 17-44 17 Prob 17.22 Show reagents to bring about each conversion. (a) OH CH3 (b) CH 3 COH CH3 CH3 (c) CH3 COH CH3 CH3 (d) CH3 COH COOH CH3 CH3 CCOOH CH3 CH3 CH3 CHCOOH CH 3 CH3 CHCH 2 COOH CH3 (e) CH3 CH= CHCH 3 CH3 CH= CHCH 2 COOH 17-45 17 Prob 17.23 Show how to synthesize butanedioic acid starting with acetylene and formaldehyde. HO Acetylene OH 2-Butyne-1,4-diol O HO OH 1,4-Butanediol HO OH O Butanedioic acid (Succinic acid) 17-46 17 Prob 17.24 Propose a mechanism for the rearrangement of benzil to sodium benzilate. OO H2 O Ph-C-C-Ph NaOH Benzil (an -diketone) HO O + - + Ph-C-C-O Na Ph Sodium benzilate HCl H2 O HO O Ph-C-C-OH Ph Benzilic acid 17-47 17 Prob 17.33 Show how to convert trans-3-phenyl-2-propenoic (cinnamic acid) to each compound. (a) C6 H5 OH O (b) C6 H5 (c) C6 H5 OH OH 17-48 17 Prob 17.34 Show how to convert 3-oxobutanoic acid to these compounds. OH O (a) (b) OH OH OH (c) O OH 17-49 17 Prob 17.35 Complete each example of Fischer esterification. (a) O H+ + OH HO COOH (b) + CH3 OH H+ COOH O (c) HO OH + H+ OH O 17-50 17 Prob 17.37 Name the carboxylic acid and alcohol from which each ester is derived. O (a) (b) O O O O O (c) O O O (d) O O O 17-51 17 Prob 17.39 Propose a mechanism for this reaction. O CH3 RCOH + CH2 =CCH3 + H O CH3 RCOCCH3 CH3 2-Methylpropene (Isobutylene) A tert-butyl ester 17-52 17 Prob 17.40 Draw a structural formula for the product of thermal decarboxylation of each compound. O (a) C6 H5 CCH 2 COOH (c) COOH (b) C6 H5 CH2 CHCOOH O CCH3 COOH 17-53 17 Prob 17.41 Propose a mechanism for each decarboxylation. Compare your mechanisms with the mechanism for decarboxylation of a -ketoacid. CH3 (a) Br- CH2 -C COO- Na + heat CH3 CH2 = C( CH3 ) 2 + CO 2 + N a+ Br- (b) CH- CH -COO - N a+ heat Br Br CH= CHBr + CO 2 + N a+ Br17-54 17 Prob 17.43 Show how to convert cyclohexane to cyclohexanecarboxylic acid. COOH 17-55 17 Carboxylic Acids End Chapter 17 17-56