Chapter 14 Carboxylic Acid Derivatives:Nucleophilic Acyl Substitution14.1 Carboxylic Acid Derivatives andNomenclature 14.2 Structure of carboxylic acid derivatives 14.3 Preparation of carboxylic acid derivatives 14.4 Nucleophilic substitution at the acylcarbon 14.4.1 Hydrolysis 14.4.2 Reactions with alcohols 14.4.3 Reactions with amines14. 5 Reduction 14.5.1 Reduction by LiAlH4 (LAH) andits derivatives 14.5.2 Reduction by Na 14.5.3 Reaction with Grignard reagents 14.6 Reactions of amides 14.6.1 Dehydration of amides 14.6.2 The Hofmann Rearrangement 14.7 Spectroscopic analysis of carboxylicacid derivativesPropanoyl chloride 丙酰氯Acyl halides 酰卤Acetic anhydride 乙酸酐Carboxylic acid anhydrides 酸 酐Propanoic acidEsters 酯Acetic acidEthyl acetate 乙酸乙酯Acetic acidPropanoyl chlorideAcetic anhydrideEthyl acetateP309, 10.1Benzoic acidEthyl benzoate （苯甲酸乙酯）14.1 Carboxylic Acid Derivatives and Nomenclatures Acetamide 乙 酰胺N-Methylbenzamide N- 甲基苯甲 酰胺N,N-Dimethylform- amide (DMF) N, N- 二甲基甲 酰胺Amides 酰胺Acetic acidAcetamideNitrile 腈Benzonitrile 苄腈Phenyl cyanide 苯基氰Benzoic acidBenzonitrile4-Methylpentanenitrile 4-甲基戊腈ROLA common feature of carboxylic acid derivatives: Hydrolysis to carboxylic acids14.2 Structure of carboxylic acid derivativesp - Conjugation+C Effect:14.3 Preparation of Carboxylic AcidDerivatives14.3.1 Preparation of Acyl HalidesSOCl2(Thionyl chloride) PBr3(Phosphorous tribromide) 14.3.2 Preparation of Acid Anhydride14.3.3 Preparation of Esters14.3.4 Preparation of Amides14.4 Nucleophilic substitution at the acyl carbon 14.4.1 HydrolysisP318,10.5Ch.P390Mechanism:Saponification(皂 化 反应)Step 1 Nucleophilic addition of hydroxide ionto carbonyl group.Base-promoted hydrolysis of ester Hydrolysis of Acyl halides is catalyzed by a base.Hydrolysis of Acid anhydridesEstersAmidesCatalyzed by a acid or a base.P331Step 2 Elimination of leaving group to restorecarbonyl group:Step 3 Proton transfer to yield alcohol and carboxylate ion:14.4.2 Reactions with alcohols Acyl halides Acid anhydrides Esters NitrilesAlcohols orphenolsEstersHydrolysis of Nitriles:P320Reactivity of carboxylic acid derivatives:Benzoyl chlorideEthyl benzoate (80%)EstersAlcoholsEsters(Exchange of esters)Salicylic acid (水杨酸)Asprin (阿司匹林)Methyl acrylate （丙烯酸甲酯）Butyl alcohol （丁醇）Butyl acrylate (丙烯酸丁酯) (94%)Alcoholysis of Nitriles:Ch.P391BenzoylchloridePiperidine（哌啶）N-Benzoyl-Piperidine（N-苯甲酰哌啶）（87-91%）Ethyl Floroacetate （氟乙酸乙酯）Floroacetamide （氟乙酸酰胺） (90%)14.4.3 Reactions with amines Acyl halides Carboxylic acid anhydrides EstersAmmonia or aminesAmides14. 5 Reduction 14.5.1 Reduction by LiAlH4 (LAH) andits derivatives1) LiAlH(OR)3Acyl halides Amides2) H2OAldehydesAmides NitrilesAminesLiAlH4Acryl halides Carboxylic acid Acid anhydrides EstersPrimary alcoholsLiAlH414.4.2 Reduction by Na Bouveault - Blanc reductionEsters NaEthanol Butanol Pentanolreflux Primary alcoholsEthyl oleate 油酸乙酯Oleic alcohol 油醇The unique method for the preparation of unsaturated primary alcohols in industryCh. P39314.5.3 Reaction with Grignard reagents1 mol RMgXLow temperatureRMgXKetonesTertiary alcoholsCarboxylic acid derivativesRMgXReactions of nitriles with Grignard reagents Addition1. RMgX Imine 亚胺Nitriles2. H2OHydrolysisKetonesRLi reacts in the same way and are oftenused instead of RMgX 14.6 Reactions of amides 14.6.1 The dehydration of amidesAmidesDehydrating agents: P4O10 (P2O5), （脱水剂） (CH3CO)2O Heating To form nitrils2-Methylpropanamide 2-甲基丙酰胺2-Methylpropanenitrile 2-甲基丙腈 （69-86%）Br2 / OH Carbonyl group had been plucked out 14.6.2 The Hofmann Rearrangement（Hofmann 降解反应） N-unsubstituted amidesto form primary amines having one lesscarbon atom than amideMechanism: Step 1 Formation of an N-bromo amideintermediate:Deprotonation of amideAmide nitrogen anionas a nucleophileCh.P396, (丙)Step 2 Rearrangement of the N-bromo amideto an isocyanate（异氰酸酯）Deprotonation of N-bromo amide, the group R migrates from C atom to N atom to form an isocyanate. Step 3 Hydrolysis of isocyanate by base- catalyzedCarbamic acid (异氰酸)dissociates to an amine and CO2The features of Hofmann rearrangement: 1. N-unsubstituted amides as substrates 2. Rearrangement proceeds with retentionof configuration at migrating group(S)-2-Methyl- 3-Phenylpropanamide(S)-1-Phenyl-2-propanamine14. 7 Spectroscopic analysis of carboxylicacid derivatives Table 1. The stretching frequency of C=OIR:The stretching frequency of: 22102260 cm-1CompoundsStretching frequency of C=O (cm-1)RCOCl (RCO)2OR CO2R RCONH218151785 18501800 and 17801740 1735 16801630Esters Carboxylic acid anhydridesStretching frequency of CO: 1310 1050 cm-1Amides: Stretching frequency of N H bond:3500 3200 cm-1 - H : 2 3 ppm1H NMR:13C NMR: 120 ppm Amide: N - H : 5 8 ppmProblems to chapter 14 P 34610.31 (a),(d),(e)10.32(c)(g)10.33(b),(d),(g)10.3710.3910.4110.42 (a),(c)10.4510.46(a), (c)10.4710.5510.56(b)10.57 10.58 10.59 10.60 10.61 10.62