UNIVERSITY OF NAIROBI COLLEGE OF BIOLOGICAL AND PHYSICAL SCIENCES SCHOOL OF PHYSICAL SCIENCES IN COLLABORATION WITH

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1 UNIVERSITY OF NAIROBI COLLEGE OF BIOLOGICAL AND PHYSICAL SCIENCES SCHOOL OF PHYSICAL SCIENCES IN COLLABORATION WITH THE CENTRE FOR OPEN AND DISTANCE LEARNING SCH 302: ORGANIC CHEMISTRY 3 SELF STUDY MODULE FOR BACHELOR OF SCIENCE AND EDUCATION (SCIENCE) DISTANCE LEARNING PROGRAMME Written By Dr. Albert Jairo Ndakala Department of Chemistry University of Nairobi i

2 Reviewed By Dr. John Mmari Onyari Department of Chemistry University of Nairobi ii

3 SCH 302: Organic Chemistry 3 Published by the University of Nairobi Council, P.O. Box 30197, Nairobi, Kenya Printed by the College of Education and External Studies, University of Nairobi, P.O. Box 30197, Nairobi, 2010 University of Nairobi Council, 2010, all rights reserved. No part of this Module may be reproduled in any form or by any means without permission in writing from the Publisher iii

4 TABLE OF CONTENTS PAGE Unit Introduction Unit Objectives Tips for the Student xviii xix xx LECTURE ONE: ALDEHYDES AND KETONES 1.1 Introduction Objectives Definition of Aldehydes and Ketones Occurrence of Aldehydes and Ketones in Nature Nomenclature of Aldehydes and ketones Common Nomenclature Aldehydes Ketones Substitutive (Systematic) Nomenclature Aldehydes Ketones Naming of Carbonyl Groups as Substituents Summary Self Assessment Test References 12 LECTURE TWO: SYNTHESIS OF ALDEHYDES AND KETONES 2.1 Introduction Objectives 14 iv

5 2.3 Synthesis of Aldehydes and Ketones Oxidation of Alcohols Oxidative Cleavage of Glycols Ozonolysis of Alkenes Hydration of Terminal Alkynes Reaction of Nitriles with Grignard Reagents Friedel-Crafts Acylation of Aromatic Compounds Reaction of Acid Chlorides with Organocuprates Properties of Aldehydes and Ketones Summary Self Assessment Test References 27 LECTURE THREE: REACTIONS OF ALDEHYDES AND KETONES 3.1 Introduction Objectives Reactions of Aldehydes and Ketones Oxidations of Aldehydes and Ketones Common Oxidizing Agents Tollens Silver Mirror Test (Silver-Ammonia Complex) Reduction of Aldehydes and Ketones Reduction using LiAlH 4 and NaBH Catalytic Hydrogenation Reductive Deoxygenation of Aldehydes and Ketones Reactions of Aldehydes and Ketones with Water: Hydration 36 v

6 3.3.5 Reactions of Aldehydes and Ketones with Alcohols: 37 Hemiacetal and Acetal Formation Acyclic Hemiacetals Cyclic Hemiacetals Applications of Acetal Chemistry in Organic Synthesis Addition of HCN to Aldehydes and Ketones: Cyanohydrin 41 Formation 3.4 Summary Self Assessment Test References 44 LECTURE FOUR: REACTIONS OF ALDEHYDES AND KETONES 4.1 Introduction Objectives Nucleophilic Addition-Elimination Reactions with Nitrogen Nucleophiles Reaction with Primary Amines and Monosubstituted Derivatives of Ammonia Reaction with Other Primary Amine Derivatives Reactions with Secondary Amines Addition of Grignard, Organolithium and Sodium Acetylide Reagents to Aldehydes and Ketones Grignard Reagents Organolithium and Sodium Acetylide Reagents The Wittig Reaction: Addition-Elimination Reaction Summary vi

7 4.5 Self Assessment Test References 54 LECTURE FIVE: REACTIONS OF ALDEHYDES AND KETONES 5.1 Introduction Objectives Enols and Enolates (Keto-Enol Tautomerism) The Chemistry of Enols and Enolates of Aldehydes and Ketones Halogenation of Aldehydes and Ketones The Environmental and Health Implications of the Chemistry of Enolization during Water Treatment with Chlorine Alkylation of Enolates The Aldol Addition and Condensation Reaction Self-Aldol Additions and Condensation of Aldehydes and Ketones Cross-Aldol Aldol Addition and Condensations of Aldehydes and Ketones Claisen-Schmidt Condensation Intramolecular Aldol Condensations Synthetic Applications of Aldol Additions and Condensations Other Condensations Cannizzaro Reaction Summary Self Assessment Test vii

8 5.7 References 75 LECTURE SIX: CARBOXYLIC ACIDS 6.1 Introduction Objectives Definition and Occurrence of Carboxylic Acids Nomenclature of Monocarboxylic Acids Common Nomenclature of Carboxylic Acids Systematic Nomenclature of Carboxylic Acids Nomenclature of Dicarboxylic Acids Properties of Carboxylic Acids Physical Properties Acidity of Carboxylic Acids Acidity of Aliphatic Carboxylic Acids Acidity of Aromatic Carboxylic Acids Summary Self Assessment Test References 91 LECTURE SEVEN: SYNTHESIS OF CARBOXYLIC ACIDS 7.1 Introduction Objectives Synthesis of Carboxylic Acids Oxidation of Primary Alcohols Oxidation of Aldehydes Ozonolysis of Alkenes and Alkynes 95 viii

9 7.3.4 Malonic Ester Synthesis of Carboxylic Acids Hydrolysis of Nitriles Carboxylation of Grignard Reagents Summary Self Assessment Test References 100 LECTURE EIGHT: REACTIONS OF CARBOXYLIC ACIDS 8.1 Introduction Objectives Reactions of Carboxylic Acids Bicarbonate Test for Carboxylic Acids Salt Formation Reaction at the Carboxylate Oxygen Esterification by Alkylation on the Carboxylate Oxygen Reaction at the Carbonyl Carbon Acid-Catalysed Esterification of Carboxylic Acids Esterification by Activation of the Carboxyl Group Reaction of Carboxylic Acids with Amines Salt Formation Amide Formation Reduction of Carboxylic Acids to Alcohols Reaction of Carboxylic Acids with Thionyl Chloride and Phosphorus Halides Decarboxylation of Carboxylic Acids (Loss of the Carboxyl Group as CO 2 ) ix

10 Keto Acids Malonic Acid Derivatives Summary Self Assessment Test References 115 LECTURE NINE: ACID CHLORIDES AND ACID ANHYDRIDES 9.1 Introduction Objectives Common Carboxylic Acid Derivatives Definition of Acid Chlorides Nomenclature of Acid Chlorides Physical Properties of Acid Chlorides Preparation of Acid Chlorides Reactions of Acid Chlorides Hydrolysis of Acid Chlorides Reaction with Alcohols or Phenols Reaction with Ammonia or Amines Partial Reduction of Acid Chlorides to Aldehydes Reaction of Acid Chlorides with Lithium Dialkylcuprates Reaction of Acid Chlorides with Arenes Summary Definition of Acid Anhydrides Nomenclature of Acid Anhydrides Physical Properties of Acid Anhydrides 125 x

11 9.6.3 Preparation of Acid Anhydrides Reactions of Acid Anhydrides Hydrolysis of Acid Anhydrides Reactions with Alcohols or Phenols Reaction with Ammonia or Amines Summary Self Assessment Test References 131 LECTURE TEN: ESTERS 10.1 Introduction Objectives Definition of Esters Nomenclature of Esters of Carboxylic Acids Physical Properties of Esters Preparation of Esters Acid-Catalysed Esterification of a Carboxylic Acid Reactions of Acid Chlorides with Alcohols Reaction of Acid Anhydrides with an Alcohol Reactions of Esters Hydrolysis of Esters Reaction with Ammonia and Amines The Hydroxamate Test Transesterification Reduction of Esters to Alcohols 140 xi

12 Reaction of Esters with Grignard Reagents Claisen Condensation Intramolecular Claisen Condensation Crossed Claisen Condensation Synthetic Applications of Esters Malonic Ester Synthesis Acetoacetic Ester Synthesis Summary Self Assessment Test References 150 LECTURE ELEVEN: AMIDES AND NITRILES 11.1 Introduction Objectives Definition of Amides Classification of Amides Nomenclature of Amides Physical Properties of Amides Preparation of Amides Reaction of Carboxylic Acids and Amines Reaction of Acid Chlorides with Amines Reaction of Acid Anhydrides with Amines Reaction of Esters with Amines Reactions of Amides Hydrolysis of Amides 157 xii

13 Reduction of Amides to Amines Hofmann Degradation Summary Definition of Nitriles Nomenclature of Nitriles Physical Properties of Nitriles Preparation of Nitriles Nucleophilic Substitution by Cyanide Ion on Alkyl 165 Halides Dehydration of Primary Amides Reactions of Nitriles Hydrolysis of Nitriles Reduction of Nitriles to Amines Reaction of Nitriles and Grignard Reagents Nomenclature of Acid Derivatives as Substituents Summary Self Assessment Test References 172 LECTURE TWELVE: PHENOLS 12.1 Introduction Objectives Definition of Phenols Nomenclature of Phenols Common Nomenclature Substitutive Nomenclature 175 xiii

14 12.5 Physical Properties of Phenols Acidity of Phenols Effects of Substituents on the Acidity of Phenols Acidities of Isomeric Phenols Summary Self Assessment Test References 188 LECTURE THIRTEEN: PREPARATION AND REACTIONS OF PHENOLS 13.1 Introduction Objectives Preparation of Phenols Industrial Synthesis of Phenol Preparation of Other Substituted Phenols Nucleophilic Aromatic Substitution Hydrolysis of Diazonium Salts Reactions of Phenols Reactions with Strong Bases Esterification Etherification of Phenols (Williamson Ether Synthesis of Aryl Ethers) Identification of Phenols Halogenation Nitration Nitrosation xiv

15 Sulphonation Friedel-Crafts Alkylation Carboxylation of Phenols (Kolbe-Schmitt Reaction) Oxidation of Phenols to Quinones Applications of Phenols in Life Summary Self Assessment Test References 205 LECTURE FOURTEEN: AMINES 14.1 Introduction Objectives Definition of Amines Classification of Amines Nomenclature of Amines Common Nomenclature IUPAC Nomenclature of Amines Priority of Citation of Principal Groups Nomenclature of Heterocyclic Amines Physical Properties of Amines Basicity of Amines Variation of Basicity among Alkylamines Basicity of Arylamines Summary Self Assessment Test References 221 xv

16 LECTURE FIFTEEN: SYNTHESIS OF AMINES 15.1 Introduction Objectives Synthesis of Amines Direct Alkylation of Ammonia and Amines Gabriel Synthesis of Primary Amines Reduction of Azides to Primary Amines Reduction of Nitriles to Primary Amines Reduction of Amides to Amines Reduction of Nitro Compounds to Primary Amines Reductive Amination Preparation of Amines by Hoffmann Rearrangement Summary Self Assessment Test References 231 LECTURE SIXTEEN: REACTIONS AND APPLICATIONS OF AMINES 16.1 Introduction Objectives Reactions and Applications of Amines Reactions of Amines with Strong Acids: Salt Formation Reactions of Amines with Carboxylic Acids Applications of Chiral Amines as Resolving Agents Coupling of Amines with Carboxylic Acids Application in the Synthesis of an Insect Repellent 236 xvi

17 Reactions of Amines with Acid Chlorides Application in the Synthesis of an Insect Repellent Reaction of Amines with Sulphonyl Chlorides: Synthesis 237 of Sulphonamides Application in the Synthesis of Sulphanilamide Reaction of Amines with Acid Anhydrides Applications in the Synthesis of an Antipyretic Drug Reactions of Amines with Nitrous Acid: Diazotization Conversion of Arylamines to Nitriles, Phenols and Aryl 240 Halides Applications in the Synthesis of Indicator Dyes Summary Self Assessment Test References 244 Sample Past Papers 245 xvii

18 UNIT INTRODUCTION SCH 302 (Organic Chemistry 3) is the third organic chemistry unit covered in the programmes leading towards the award of the Degrees of Bachelor of Science and Bachelor of Education (Science) of the University of Nairobi. It is offered after students have covered SCH 102 (Organic Chemistry 1: Introduction to Organic Chemistry) and SCH 202 (Organic Chemistry 2: Alkenes, Alkynes, Aromatic Compounds, Spectroscopy). In this unit, you will cover the chemistry of aldehydes, ketones, carboxylic acids and their derivatives, phenols and then conclude with amines. In the first part of the unit, we will explore various facets of the chemistry of aldehydes, ketones, carboxylic acids and their derivatives. During this coverage, you will gain an appreciation of the synthetic applications of their chemistry under the topics dealing with Aldol Addition and Condensation, Claisen Condensation, Malonic ester and Acetoacetic ester synthesis. We will then take a brief look at the chemistry of phenols and their applications in life and then conclude the unit by delving into the chemistry of amines and their derivatives. Their industrial application and use in addressing the health challenges of the world will also be highlighted. Your grasp of the knowledge of the subject matter of this unit will be examined through laboratory practicals (5%), tutorials (5%), continuous assessment tests (20%) and a final exam (70%). xviii

19 By the end of this unit, you shoud be able to: UNIT OBJECTIVES (i) State the defining features and occurrence of aldehydes, ketones, carboxylic acids and their derivatives, phenols and amines. (ii) Provide structural formulas for some common natural aldehydes, ketones, carboxylic acids and their derivatives, phenols and amines. (iii) Name various aldehydes, ketones, carboxylic acids and their derivatives, phenols and amines. (iv) Highlight the common methods by which aldehydes, ketones, carboxylic acids and their derivatives, phenols and amines are synthesized. (v) List the common reactions of aldehydes, ketones, carboxylic acids and their derivatives, phenols and amines. (vi) Propose reasonable and stepwise reaction mechanisms for the reactions involving aldehydes, ketones, carboxylic acids and their derivatives, phenols and amines. (vii) List the common carbanion reactions and their synthetic applications. xix