Carboxylic Acids and Derivatives: Synthesis, Reactions, and Analysis - Prof. Sushama A. Da, Study notes of Organic Chemistry

Download Carboxylic Acids and Derivatives: Synthesis, Reactions, and Analysis - Prof. Sushama A. Da and more Study notes Organic Chemistry in PDF only on Docsity! CHEM2380 DANDEKAR CHAPTER 18 9ed 1 CHAPTER 18 CARBOXYLIC ACIDS & DERIVATIVES - INTRODUCTION, NOMENCLATURE, PHYSICAL PROPERTIES - SYNTHESIS, REACTIONS: - CARBOXYLIC ACIDS - ACYL HALIDES - ACID ANHYDRIDES - ESTERS - AMIDES - NITRILES - DERIVATIVES OF H2CO3 - DECARBOXYLATION OF RCO2H - CHEMICAL ANALYSES CHEM2380 DANDEKAR CHAPTER 18 9ed 2 INTRODUCTION: - CARBOXYLIC ACIDS: RCO2H - DERIVATIVES: - SEE TABLE 18.1 p. 779 - COMMON FEATURES ? NOMENCLATURE, PHYSICAL PROPERTIES: - CARBOXYLIC ACIDS: R C OH O ALKANOIC ACID - DO PROBLEM: 18.1 p. 781 - SALTS: e.g. RCO2– Na+ (K+) - SODIUM ALKANOATE - SEE TABLE 18.2 p. 780 - SOLUBILITY - LOW MW v. HIGH MW - cf. SOLUBILITY OF Na+/K+ SALTS (SOAPS) CHEM2380 DANDEKAR CHAPTER 18 9ed 5 - N – SUBSTITUTED AMIDES R C N O R' H N – ALKYL ALKANAMIDE N,N – R C N O R' R" DIALKYL ALKANAMIDE DMF ( ? ) - NITRILES: e.g. R – C ≡ N ALKANENITRILE - IF –CN IS A SUBSTITUENT: “ CYANO ” DO PROBLEMS: 18.5 p. 786 18.19, 20 p. 821 CHEM2380 DANDEKAR CHAPTER 18 9ed 6 SPECTROSCOPIC ANALYSES - STUDY ON YOUR OWN ! ( MOSTLY REVIEW ! ) - DO PROBLEM : 18.36 p. 823 18.40 p. 825 SYNTHESIS OF: RCO2H - 1] FROM >C=C< : HOW ? - 2] FROM RCHO , RCH2OH : HOW ? - 3] FROM Ar-R: HOW ? - 4] FROM RCOCH3 : HOW ? - 5] FROM R-C≡N : HOW ? - 6] FROM RMgX : HOW ? - SEE p. 789-790 & p. 820 DO PROBLEMS: 18.6 – 18.8 p. 791 CHEM2380 DANDEKAR CHAPTER 18 9ed 7 REACTIONS AT ACYL CARBON: - AT THE ACYL CARBON: - Nu: – ADDITION, FOLLOWED BY ELIMINATION - SEE MECHANISM p. 792 cf. Nu: – ADDITION TO >C=O OF ALDEHYDES AND KETONES p. 791 NOTE: - ELIMINATION FACILITATED BY GROUP “ L ” : ( GOOD LEAVING GROUP ) THEN: OVERALL REACTION: SUBSTITUTION OF “ L ” WITH “ Nu ” WHY DOES SIMILAR ELIMINATION NOT OCCUR WITH ALDEHYDES & KETONES ? ( NO GOOD “ L ” ! ) - SEE p. 792 CHEM2380 DANDEKAR CHAPTER 18 9ed 10 - HYDROLYSIS? - R-CO-O-CO-R ? SYNTHESIS OF: RCO2R’ - FROM (RCO2H + R’-OH ) - SEE p. 797 - INTERMOLECULAR DEHYDRATION - MECHANISM: SEE p. 798 - SUPPORTING EVIDENCE ? - H3O+ CATALYSIS - 18O LABELING STUDIES - REVERSIBLE! - FROM : ( RCOX + R’-OH ) - SEE p. 798 & p. 795 - ROLE OF PYRIDINE ? - FROM (RCO-O-COR + R’-OH ) - SEE p. 799 & p. 796 - CYCLIC ANHYDRIDES? p. 799 - TRANSESTERIFICATION - SEE PROBLEM : 18.11 p. 799 CHEM2380 DANDEKAR CHAPTER 18 9ed 11 - CONSTRAINTS ? - EXAMINE BOILING POINTS - LACTONES - CYCLIC ESTERS - FROM : γ / δ – HYDROXY ACIDS - SEE p. 801 - INTRAMOLECULAR ESTERIFICATION - e.g. VITAMIN C: p. 802 - FROM: β – HYDROXY ACIDS - SEE p. 802 - INTRAMOLECULAR DEHYDRATION β – LACTONE ? OR α, β – UNSATURATED ACID ? - MACROCYCLIC LACTONE: - e.g. ERYTHROMYCIN A: p. 802 REACTIONS OF ESTERS - WITH RMgX: p. 531 - WITH DIBAL-H: p. 693 CHEM2380 DANDEKAR CHAPTER 18 9ed 12 - WITH LAH: p. 518 - HYDROLYSIS? - R-CO2R’ ? - ACID CATALYZED: - MECHANISM: REVERSE SYNTHESIS, p. 798 - BASE-PROMOTED: “ SAPONIFICATION ” - MECHANISM: p. 800 - SUPPORTING EVIDENCE ? - 18O LABELING STUDIES - RETENTION OF CONFIGURATION AT ALKYL CARBON [cf. ANALOGOUS REACTION WITH SULFONIC ESTERS] p. 801 - DO PROBLEMS: 18.12 , 18.13 p. 801 SYNTHESIS OF AMIDES: RCONH2 (-NHR, -NR2) - FROM : ( RCOX + H-N< ) - SEE p. 803 CHEM2380 DANDEKAR CHAPTER 18 9ed 15 - REAGENTS ? REACTIONS OF NITRILES - HYDROLYSIS: p. 807 - R-C≡N ? - WITH RMgX: p. 694 - WITH DIBAL-H: p. 693 - WITH LAH: p. 711 LACTAMS: - CYCLIC AMIDES ( cf. LACTONES ) - SEE p. 809 - e.g. PENICILLINS - β-LACTAM - ESSENTIAL FOR ANTIBACTERIAL ACTIVITY CHEM2380 DANDEKAR CHAPTER 18 9ed 16 DERIVATIVES OF CARBONIC ACID: H2CO3 : (OH)2 C = O - USE ACYL HALIDE TO MAKE THE VARIOUS DERIVATIVES - CARBONYL DICHLORIDE: O = CCl2 “ PHOSGENE ” : TOXIC ! - SN REACTIONS AT BOTH Cl GROUPS - - USE APPROPRIATE STOICHIOMETRY TO MAKE NON-SYMMETRICAL DERIVATIVES Cl-CO-Cl RO-CO-Cl RO-CO-N< - ALKYL CHLOROFORMATES & CARBAMATES - SEE p. 810 - ALKYL CHLOROFORMATES H OH O Cl OH O Cl OR O CHLOROFORMIC ? ? ACID CHEM2380 DANDEKAR CHAPTER 18 9ed 17 - CARBAMATE = (ESTER + AMIDE) ON SAME CARBON OR N< O ESTER AMIDE - USEFUL PROTECTING GROUPS IN PEPTIDE SYNTHESIS p. 811 - CAN BE REMOVED UNDER MILD CONDITIONS - H2, Pd OR cold HBr/ CH3CO2H - RELEASES FREE AMINE (+ ? +?) ALTERNATIVE SYNTHESIS OF CARBAMATES R N C OR O H R N C O H OR + - SEE p. 811