2. Chapter 13 Carboxylic acids 13.1 Nomenclature 13.2 Acidity of carboxylic acids Factors affecting the acidity of carboxylic acids Dicarboxylic acids 13.3 Preparation of carboxylic acids 13.3.1 Preparation of carboxylic acids by carbonation of Grignard reagents 13.3.2 Preparation of carboxylic acids by the preparation and hydrolysis of nitriles

3. 13.4 Reactions of Carboxylic acids 13.4.1 Esterification 13.4.2 α-Halogenation of carboxylic acids: Hell-Volhard-Zelinsky reaction 13.4.3 Decarboxylation of malonic acid and related compounds 13.5 Spectroscopic analysis of carboxylic acids

4. Carboxylic acid: Carboxyl group （羧基） Acyl group （酰基） All of carboxylic acid derivatives contain the acyl group. 13.1 Nomenclature 1. e oic acid 4-Hexenoic acid （ 4- 己烯酸） 2-Hydroxy-2- phenylethanoic acid Mandelic acid （扁桃酸） 4-Methylhexanoic acid （ 4 - 甲基己酸） 2. For the compounds with polyfunctional group carboxylic acids outrank all the common group. Ch. P281 P308

5. 3-Bromocyclohexane- carboxylic acid (3- 溴环己烷甲酸 ) 3-Bromocyclohexane- carboxylic acid (3- 溴环己烷甲酸 ) HY > RCOOH > H 2 CO 3 >C 6 H 5 OH > H 2 O > RCH 2 OH > pk a : 4 ~ 5 6.38 10 15.74 16 ~ 19 ~ 25 ~ 34 ~50 13.2 Acidity of carboxylic acids sp 2 hybridization, p - πconjugation 3-Ethyl-6-methyl octanedioic acid (3- 甲基 -6- 乙基 辛二酸 ) 3-Ethyl-6-methyl octanedioic acid (3- 甲基 -6- 乙基 辛二酸 ) 1-Cyclopentene- carboxylic acid (1- 环戊烯甲酸 ) 1-Cyclopentene- carboxylic acid (1- 环戊烯甲酸 ) 1 2 34 5

6. Stronger base Weaker base Weaker acid Stronger acid Sodium bicarbonate RCOOH: Water insoluble; RCOO - M + (Carboxylic salt): Water soluble Carboxylic acids can be separated from alcohols and phenol.

7. Factors affecting the acidity of carboxylic acids: Inductive effects of the substituents pK a 0.7 1.48 2.85 4.75 With more electron-withdrawing groups, acidity of the carboxylic acid is stronger. Inductive effects fall off rapidly as number ofσbond increases. P313,10.3

8. pK a : 2.85 4.05 4.50 2-Chlorobutanoic 3-Chlorobutanoic 4-Chlorobutanoic acid acid acid Carbon becomes more electron- withdrawing as its s character increases: sp 3 < sp 2 < sp pK a : 4.8 4.3 4.2

9. Dicarboxylic acids: Oxalic acid （草酸或乙二酸） Malonic acid （丙二酸） Heptanedionic acid （庚二酸） pK a1 : 1.2 2.8 4.3 Carboxylate group with Electron-donating (+I) Carboxylic group with electron-withdrawing (-I) Field effect （场效应） : electronic effects is transferred by space Ch.P375

10. 13.3 Preparation of carboxylic acids 13.3.1 Preparation of carboxylic acids by carboxylation （羧化作用） of Grignard reagent Grignard reagents react with carbon dioxide to yield Mg salt of carboxylic acids ， acidification （酸化） produces RCOOH 2,2-Dimethyl propanoic acid (80%) Benzoic acid (85%) Carbonation = carboxylation P316, 10.4 P316, 10.4 1) 2)Extension of C skeleton by 1 carbon atom. 3) Limitation: OH, NH, SH or C=O

11. 13.3.2 Preparation of carboxylic acids by the preparation and hydrolysis of nitriles （腈） S N 2 reaction of alkyl halide with sodium cyanide produce nitrile (alkyl cyanide) ( 烷基氰 ), Hydrolysis of nitrile yields RCOOH. 3-Hydroxy- propanenitrile 3-Hydroxy- propanoic acid Ch.P368, (2)

12. 1,5-Pentanedioic acid (83-85%) 1,3-Dibromopropane 1,5-Pentanedinitrile (77-86%) Preparation of α- hydroxy carboxylic acids 2-Pentanone cyanohydrin 2-Hydroxy- pentanoic acid (60%) Preparation of dicarboxylic acids

13. 13.4 Reactions of Carboxylic acids Acidity Nucleophilic acyl substitution Nucleophilic acyl substitution Reaction sites of carboxylic acids Reduction to CH 2 Decarboxylation 脱羧反应 Decarboxylation 脱羧反应 α-H reaction

14. 13.4.1 Esterification （酯化反应） Carboxylic acid Alcohol Ester Water Which C—O bond was broken? Mechanism of acid-catalyzed esterification: Step 1 Protonation on the carbonyl group of the carboxylic acid P322

15. Step 2 Nucleophilic attack of a molecule of alcohol to the protonated carbonyl group Tetrahedral intermediate Step 3 The proton transfers and dehydration Step 4 Deprotonation to form the ester

16. The fundamental mechanistic patterns （基本机理模式） of nucleophilic reaction of a carboxylic acid and its derivatives 1.Activation of the carbonyl group － protonation of carbonyl group 2. Nucleophilic addition to the protonated carbonyl to form a tetrahedral intermediate 3. Elimination from the tetrahedral intermediate to restore the carbonyl group P318, 10.5

17. 13.4.2α-Halogenation of carboxylic acids: Hell-Volhard-Zelinsky reaction Aliphatic carboxylic acids react with Br 2 or Cl 2 in the presence of P or PX 3 to give α- halo acids α- Halo acid Ch.P379,(5)

18. α- Halo acids are important synthetic intermediates: 2-Hydroxybutanoic acid (69%) A standard method for the preparation of α- amino acid: 2-Amino-3-methylbutanoic acid (48%)

19. 13. 4. 3 Decarboxylation （脱羧反应） of Malonic acid and related compounds Malonic acidAcetic acid Carbon dioxide Mechanism Thermal decarboxylation Thermal decarboxylation Transition state Malonic acid decarboxylates readily:

20. When α- H was replaced, decarboxylation also occurs readily. 2-(2-Cyclopentenyl) malonic acid (2-Cyclopentenyl) acetic acid (96~99%) Decarboxylation of β- keto acids leads to ketones

21. 13.5 Spectroscopic analysis of carboxylic acids IR: O － H Stretching 3500~2500 cm -1 C = O Stretching 1700 cm -1 NMR: COOH: 10-12 ppm

23. Ar － H CH 2 COOH