List of Mechanisms Wolff-Kishner Reduction (Section 16.11E) Acid-Catalyzed a-Halogenation of a Ketone (section 16.12c) Base-Promoted a Ketone( Chapter 17 Carboxylic Acids Formation of a Methyl Ester Using Decarboxylation of a B-Ketocarboxylic Acid (section 17.9A) Decarboxylation of a B-Dicarboxylic Acid (ctin) Chapter 18 Functional Derivatives of Carboxylic Acids Hydrolysis of an Acid Acid-Catalyzed Ester Hydrolysis (section 18.4c) Hydrolysis of an Ester in Aqueous Base (Saponification)(section 184c) Hydrolysis of an Amide in Aqueous Acid) Hydrolysis of an Amide in Aqueous Base (Section 18.4D) Hydrolysis of a Cyano Group to an Amide in Aqueous Base Reaction of an Acid Chloride and Ammonia(Section 18.6A) Reaction of an Ester with a Grignard Reagent ( Reduction of an Ester by Lithium Aluminum Hydride (.10A) Reduction of an Amide by Lithium Aluminum Hydride (section 18.10B) Chapter 19 Enolate Anions and Enamines Base-Catalyzed Aldol Reaction (Section 19.2A) Acid-Catalyzed Aldol Reaction (A Acid-Catalyzed Dehydration of an Aldol Product (Section 19.2A) Claisen Condensation (Section 19.3A) Alkylation of an Enamine (Section 19.5A) Michael Reaction-Conjugate Addition of Enolate Anions (Section 198A) Chapter 20 Dienes,Conjugated Systems,and Pericyclic Reactions 1.2-and 1.4-Addition to a Coniugated Diene (section 20.2A) The Claisen Rearrangement (n20.A The Cope Rearrangement(Section 20.68) Chapter 21 Benzene and the Concept of Aromaticity Kolbe Carboxylation of Phenol (Section 21.4E) Chapter 22 Reactions of Benzene and Its Derivatives Electrophilic Aromatic Substitution-Chlorination Section 22.1A) Formation of the Nitronium lon (etion Friedel-Crafts Alkylation (Section22.1c) Friedel-Crafts Acvlation-Generation of an Acylium lon (section 22.1c) Nucleophilic Aromatic Substitution via a Benzyne Intermediate Nucleophilic Aromatic Substitution by Addition-Elimination(ectin23) Unessisotelartnhn3 xxi 平可于
Unless otherwise noted all art on this page © Cengage Learning 2013 List of Mechanisms xxi Wolff-Kishner Reduction (Section 16.11E) Acid-Catalyzed a-Halogenation of a Ketone (Section 16.12C) Base-Promoted a-Halogenation of a Ketone (Section 16.12C) Chapter 17 Carboxylic Acids Formation of a Methyl Ester Using Diazomethane (Section 17.7B) Decarboxylation of a b-Ketocarboxylic Acid (Section 17.9A) Decarboxylation of a b-Dicarboxylic Acid (Section 17.9B) Chapter 18 Functional Derivatives of Carboxylic Acids Hydrolysis of an Acid Chloride (Section 18.4A) Acid-Catalyzed Ester Hydrolysis (Section 18.4C) Hydrolysis of an Ester in Aqueous Base (Saponification) (Section 18.4C) Hydrolysis of an Amide in Aqueous Acid (Section 18.4D) Hydrolysis of an Amide in Aqueous Base (Section 18.4D) Hydrolysis of a Cyano Group to an Amide in Aqueous Base (Section 18.4E) Reaction of an Acid Chloride and Ammonia (Section 18.6A) Reaction of an Ester with a Grignard Reagent (Section 18.9A) Reduction of an Ester by Lithium Aluminum Hydride (Section 18.10A) Reduction of an Amide by Lithium Aluminum Hydride (Section 18.10B) Chapter 19 Enolate Anions and Enamines Base-Catalyzed Aldol Reaction (Section 19.2A) Acid-Catalyzed Aldol Reaction (Section 19.2A) Acid-Catalyzed Dehydration of an Aldol Product (Section 19.2A) Claisen Condensation (Section 19.3A) Alkylation of an Enamine (Section 19.5A) Michael Reaction—Conjugate Addition of Enolate Anions (Section 19.8A) Chapter 20 Dienes, Conjugated Systems, and Pericyclic Reactions 1,2- and 1,4-Addition to a Conjugated Diene (Section 20.2A) The Claisen Rearrangement (Section 20.6A) The Cope Rearrangement (Section 20.6B) Chapter 21 Benzene and the Concept of Aromaticity Kolbe Carboxylation of Phenol (Section 21.4E) Chapter 22 Reactions of Benzene and Its Derivatives Electrophilic Aromatic Substitution—Chlorination (Section 22.1A) Formation of the Nitronium Ion (Section 22.1B) Friedel-Crafts Alkylation (Section 22.1C) Friedel-Crafts Acylation—Generation of an Acylium Ion (Section 22.1C) Nucleophilic Aromatic Substitution via a Benzyne Intermediate (Section 22.3A) Nucleophilic Aromatic Substitution by Addition-Elimination (Section 22.3B) Copyright 2013 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it
List of Mechanisms Chapter 23 Amines Formation of the Nitrosyl Cation (Section23.) Reaction of a2 Amine with the Nitrosyl Cation to Give an N-Nitrosamine (ection Reaction of a 1 Amine with Nitrous Acid (Section 23.8D) The Tiffeneau-Demjanov Reaction (ection.D) The Hofmann Elimination (Section 23.9 The Cope Elimination (Section2310) Chapter 24 Catalytic Carbon-Carbon Bond Formation The Heck Reaction (Section24.3B) The Catalytic Cycle for Allylic Alkylation (.4A) The Catalytic Cycle of Cross-Coupling (Seetion 24.5A) Chapter 26 Lipids Oxidation of a Fatty Acid-CH2-CH2-to-CH-CH-by FAD (Section 26.2c) Chapter 27 Amino Acids and Proteins Cleavage of a Peptide Bond at Methionine by Cyanogen Bromide (section 27.4B Edman Degradation -Cleavage of an N-Terminal Amino Acid Chapter 29 Organic Polymer Chemistry Radical Polymerization of a Substituted Ethylene(A Ziegler-Natta catalysis of Ethvlene Polymerization (section 29.68) Homogeneous Catalysis for Ziegler-Natta Coordination Polymerization (ti Initiation of Anionic Polymerization of Alkenes (section29.D) Initiation of Anionic Polymerization of Butadiene (Section 29.6D Initiation of Cationic Polymerization of an Alkene by HF.BF) Initiation of Cationic Polymerization of an Alkene by a Lewis Acid (Section 29.6D) xxii
Unless otherwise noted all art on this page © Cengage Learning 2013 List of Mechanisms xxii Chapter 23 Amines Formation of the Nitrosyl Cation (Section 23.8) Reaction of a 2° Amine with the Nitrosyl Cation to Give an N-Nitrosamine (Section 23.8C) Reaction of a 1° Amine with Nitrous Acid (Section 23.8D) The Tiffeneau-Demjanov Reaction (Section 23.8D) The Hofmann Elimination (Section 23.9) The Cope Elimination (Section 23.10) Chapter 24 Catalytic Carbon-Carbon Bond Formation The Heck Reaction (Section 24.3B) The Catalytic Cycle for Allylic Alkylation (Section 24.4A) The Catalytic Cycle of Cross-Coupling (Section 24.5A) Chapter 26 Lipids Oxidation of a Fatty Acid !CH2!CH2! to !CH"CH! by FAD (Section 26.2C) Chapter 27 Amino Acids and Proteins Cleavage of a Peptide Bond at Methionine by Cyanogen Bromide (Section 27.4B) Edman Degradation—Cleavage of an N-Terminal Amino Acid (Section 27.4B) Chapter 29 Organic Polymer Chemistry Radical Polymerization of a Substituted Ethylene (Section 29.6A) Ziegler-Natta Catalysis of Ethylene Polymerization (Section 29.6B) Homogeneous Catalysis for Ziegler-Natta Coordination Polymerization (Section 29.6B) Initiation of Anionic Polymerization of Alkenes (Section 29.6D) Initiation of Anionic Polymerization of Butadiene (Section 29.6D) Initiation of Cationic Polymerization of an Alkene by HF?BF3 (Section 29.6D) Initiation of Cationic Polymerization of an Alkene by a Lewis Acid (Section 29.6D) Copyright 2013 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it
Preface INTRODUCTION This se the objectives:the first is to learn organic chemistry,and the second is to establish the intellectual foundation for other molecular science courses.Most often,these other Th anic red tes he rd gi students a fundamental u standing of organic molecules and reactions as well as their mechanisms and uses in organic synthesis.The text then builds on the fundamentals by emphasizing bridging concepts that will prepare students to subsequent science courses.Several studying ng f ns text Organic Chemistry Reaction Roadmaps. A FRESH LOOK AT MECHANISMS o aing organic chemistry ments in a special primer section preceding Chapter6.In addition,a new special primer section just before Chapter 18 describes how to apply this unique approach ocomy the me mecnansms tor mhe reacnons or carboync acd denvacs ns orica reak pot students arning to develop and stan wgonloctonsthemeohanismclememisaeepl6incdndetal,ncodg ibed as combinations of these individ ual mec anism el ments which are written in stepwise shion.This new approach not only simplifies the prediction of reaction mechanisms simpler,analogous to a multiple-choice situa- tion in which the correct mechanism element is chosen from a menu of choices.Also Common Mistakes in Arrow Pushing,"gives students more hints on foe the mechanism roach.the unitin philes reacting with electrophiles is highlighted.Especially helpful is the use of electrostatic potential surface models of reacting molecules.These maps emphasize, n an ea d,lc fashion,how themaortyv Unless otherwise noted all art on this page Cengage Leaming 2013 xxiii
Unless otherwise noted all art on this page © Cengage Learning 2013 xxiii InTroduCTIon This seventh edition of Organic Chemistry significantly extends the transformation started in the sixth edition. Students taking an organic chemistry course have two objectives: the first is to learn organic chemistry, and the second is to establish the intellectual foundation for other molecular science courses. Most often, these other courses involve biochemistry or specialized topics such as materials science. This textbook addresses these two objectives head-on by first presenting mechanistic and synthetic organic chemistry geared toward giving students a fundamental understanding of organic molecules and reactions as well as their mechanisms and uses in organic synthesis. The text then builds on the fundamentals by emphasizing bridging concepts that will prepare students for subsequent science courses. Several studying and learning features of this text include comprehensive end-of-chapter summaries, a unique paradigm for learning mechanisms, and an enhanced learning tool called Organic Chemistry Reaction Roadmaps. A FrESH Look AT MECHAnISMS This edition refines a revolutionary paradigm for learning organic chemistry mechanisms. Students are introduced to a small set of individual mechanism elements in a special primer section preceding Chapter 6. In addition, a new special primer section just before Chapter 18 describes how to apply this unique approach to construct the mechanisms for the reactions of carboxylic acid derivatives, historically the make-or-break point for students learning to develop and understand complex reaction mechanisms in the organic chemistry course. In both of these new special sections, the mechanism elements are explained in detail, including when they are appropriate to use. Reaction mechanisms throughout the rest of the book are described as combinations of these individual mechanism elements, which are written in stepwise fashion. This new approach not only simplifies the learning of mechanisms for students but also makes it easier to recognize similarities and differences between related reactions. Most important, it makes the prediction of reaction mechanisms simpler, analogous to a multiple-choice situation in which the correct mechanism element is chosen from a menu of choices. Also, Appendix 10, “Common Mistakes in Arrow Pushing,” gives students more hints on writing mechanisms. To reinforce the mechanism element approach, the uniting concept of nucleophiles reacting with electrophiles is highlighted. Especially helpful is the use of electrostatic potential surface models of reacting molecules. These maps emphasize, in an easily interpreted, color-coded fashion, how the majority of reactions involve areas of higher electron density on one reactant (a nucleophile) interacting with areas of lower electron density on the other reactant (an electrophile). Preface Copyright 2013 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it
Preface A FRESH LOOK AT SYNTHESIS:ORGANIC CHEMISTRY ROADMAPS,AN INNOVATIVE AND POWERFUL WAY TO VISUALIZE ORGANIC REACTIONS sentation of the different organic reactions taught in the context of the impor analogous to s are us to repre ing for organic chemistry students even though synthesis is at the core of organi chemistry as a discipline.The power of the organic chemistry reaction roadmap is that it h lps stu e reactions to reaction rdmuheend-ofhapr Chapter 6 and presented in complete form in a new Appendix 11,which students can tear out and use next to a problem. A FRESH LOOK AT ORBITALS An organic chemist's theoretical framework for understanding electron density within molecules is based on atomic and molecular orbitals.Paradoxically,organic ovide only passing covera ing thei he e ea interplay between the two complementary approaches to orbital descriptions valence bond theory and molecular orbital theory.Chapter 1 provides a compre. hensive description of how organic chemists use electronic theory to understand and are given easy-to- situations.such as molecules described by multinle res tures.The inclusion of calculated orbital diagrams alongside the familiar orbital cartoons gives students a sizes and shapes that are students v into molecular structure and reactivity A FRESH LOOK AT MCAT PREPARATION A significan or PCAT O doingso t content on the MCAT is in the form of passages followed by a series of multiple-choice to develop increas reading comprehension an an Passage and Questions).The passages cover interesting applications of organic chemistry principles as well as biological and chemical topics.Thus,far from tion,these passages add considerable enrichment to the materia ng prese xxiv
Unless otherwise noted all art on this page © Cengage Learning 2013 Preface xxiv A FrESH Look AT SynTHESIS: orgAnIC CHEMISTry roAdMAPS, An InnoVATIVE And PoWErFuL WAy To VISuALIzE orgAnIC rEACTIonS In this seventh edition, we refine an innovation to organic chemistry learning that we refer to as the Organic Chemistry Reaction Roadmap. It is a graphical representation of the different organic reactions taught in the context of the important functional groups. The functional groups of an organic chemistry roadmap are analogous to cities on a real roadmap, and the reactions are like the roads between those cities. Arrows are used to represent known routes between functional groups, and the reagents required to bring about each reaction are written next to the corresponding arrow. Multistep synthesis questions are often very challenging for organic chemistry students even though synthesis is at the core of organic chemistry as a discipline. The power of the organic chemistry reaction roadmap is that it helps students visualize the reactions to interconvert key functional groups in multistep synthesis problems. The construction and use of organic chemistry reaction roadmaps are introduced in the end-of-chapter problems beginning in Chapter 6 and presented in complete form in a new Appendix 11, which students can tear out and use next to a problem. A FrESH Look AT orBITALS An organic chemist’s theoretical framework for understanding electron density within molecules is based on atomic and molecular orbitals. Paradoxically, organic chemistry texts generally provide only passing coverage of orbitals, never revealing their true shapes or full significance. The seventh edition paints a detailed picture of the orbital nature of electron density in Chapter 1 by focusing on the interplay between the two complementary approaches to orbital descriptions: valence bond theory and molecular orbital theory. Chapter 1 provides a comprehensive description of how organic chemists use electronic theory to understand structure, bonding, and reactivity. Significantly, students are given easy-to-use guidelines that detail when and how to use electronic theory, even in complex situations, such as molecules described by multiple resonance contributing structures. The inclusion of calculated orbital diagrams alongside the familiar orbital cartoons gives students a greater appreciation for orbital sizes and shapes that are reinforced throughout the book. The intent is to provide students with a strong theoretical foundation that will give them unprecedented insight and intuition into molecular structure and reactivity. A FrESH Look AT MCAT PrEPArATIon A significant number of students taking organic chemistry are doing so to prepare for standardized tests such as the MCAT, DAT, or PCAT. Often, organic chemistry content on the MCAT is in the form of passages followed by a series of multiple-choice questions. Learning to answer questions based on passages requires students to develop increased reading comprehension and analytical skills. The seventh edition of Organic Chemistry is the first text to aid students in developing these skills by introducing an extensive series of passages followed by several thoughtprovoking multiple-choice questions in almost every chapter (MCAT Practice: Passage and Questions). The passages cover interesting applications of organic chemistry principles as well as biological and chemical topics. Thus, far from being just test preparation, these passages add considerable enrichment to the material being presented. ROADMAP R E A C T I O N Copyright 2013 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it
ORGANIC CHEMISTRY APPLIED TO THE SYNTHESIS Preface OF COMPLEX MOLECULES hCghheawnewccngmgnhca5pmsegaofwhdhsodcnon strate to students how synthetic organic chemistry is used in pharmaceutical research and in the productio of us to the syn til es such a p svnthesis problems challeng students to develop their own multistep plan for converting a relatively simple starting material into a more complex target e.Multistep syr thesis is supported by an expanded description of retrosyn whe to use certan omple structu ORGANIC CHEMISTRY APPLIED TO BIOLOGY erePp0Ptet example,the organic chemistry of amino acids is highlighted beginning in Section 3.8, ongwith the importance of alkene geo ed ogen b ing is ino added throug hout the book,not just at the end,because not all instructors make i through the biological chemistry chapters at the end of the text.Relevance to practical application is a o emphasized in an expand ed array of essays titled Chen tion 18 science conc ots such as spider silk(Chemical Connections:Section 276).These sections provide a bridge between the theory of organic chemistry and well-known, emistry essays can be found on the inside ba MASTERING SKILLS his end 1o boxes gh ht“sui organic ch nts the Hbrid 8 Dram and reco nize Enantiomers and Diastereomers,How To Retro Amine into the Proper Starting Materials for a Reductive Amination,and How To Recognize Aromatic Compounds:Criteria and Caveats HELPING STUDENTS PREPARE MORE EFFICIENTLY A key feature of the seventh edition is the end-of-chapter summaries,which are min study guides designed to help students prepare for class exams and later for standard- nless otherwise noted all art on this page Cengage Leaming 2013 XXV
Unless otherwise noted all art on this page © Cengage Learning 2013 Preface xxv Organic chemistry applied tO the synthesis Of cOmplex mOlecules Organic chemistry enables the synthesis of thousands of useful molecules. Synthetic applications of the reactions covered in this text are emphasized throughout, partly through the many new challenging synthesis problems, the goal of which is to demonstrate to students how synthetic organic chemistry is used in pharmaceutical research and in the production of useful pharmaceuticals. The text provides applications of the reactions to the synthesis of important molecules, such as Valium, fluoxetine (Prozac), meperidine (Demerol), albuterol (Proventil), tamoxifen, and sildefanil (Viagra). Multistep synthesis problems challenge students to develop their own multistep synthetic plan for converting a relatively simple starting material into a more complex target molecule. Multistep synthesis is supported by an expanded description of retrosynthetic analysis in multiple chapters, including tips on recognizing when to use certain reactions, such as those involving enolates in the construction of complex structures. Organic chemistry applied tO BiOlOgy The application of organic chemistry principles to important biological molecules is integrated where appropriate to establish a bridge with biochemistry courses. In particular, Connections to Biological Chemistry gives special attention to those aspects of organic chemistry that are essential to understanding the chemistry of living systems. For example, the organic chemistry of amino acids is highlighted beginning in Section 3.8, along with the importance of alkene geometry to both membrane fluidity and nutrition. How hydrogen bonding is involved with drug-receptor interactions (Section 10.2) is discussed. Importantly, these Connections to Biological Chemistry features have been added throughout the book, not just at the end, because not all instructors make it through the biological chemistry chapters at the end of the text. Relevance to practical application is also emphasized in an expanded array of essays titled Chemical Connections. Topics include medicines such as penicillins and cephalosporins (MCAT Practice: Section 18.8), food supplements such as antioxidants (Section 8.7), and materials science concepts such as spider silk (Chemical Connections: Section 27.6). These sections provide a bridge between the theory of organic chemistry and well-known, current, practical applications. A list of the Chemical Connections as well as Connections to Biological Chemistry essays can be found on the inside back cover of this text. mastering skills Mastering organic chemistry requires the development of certain intellectual skills. To this end, 15 How To boxes highlight “survival skills” for organic chemistry students. Five new How To boxes to this edition are How To Quickly Figure Out Formal Charge, How To Quickly Recognize the Hybridization and Geometry of Atoms, How To Quickly Draw and Recognize Enantiomers and Diastereomers, How To Retrosynthetically Dissect an Amine into the Proper Starting Materials for a Reductive Amination, and How To Recognize Aromatic Compounds: Criteria and Caveats. helping students prepare mOre efficiently A key feature of the seventh edition is the end-of-chapter summaries, which are mini study guides designed to help students prepare for class exams and later for standardized tests such as the MCAT. When preparing for exams, students will benefit from the bulleted lists of important concepts with highlighted keywords. These mini study guides Copyright 2013 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it