Organic chemistry: a mechanistic approach

Organic chemistry deals with the structures, synthesis, and functions of compounds whose molecules now include assemblies up to giant biomolecules such as nucleic acids, proteins, and po

Organic

Chemistry

Periodic Table of the Elements

Howard Maskill Visiting Professor, Department of Chemical and

Biological Sciences, University of Huddersfi eld, UK

Profes University of

Howa Visit Tadashi O

1

Great Clarendon Street, Oxford, OX2 6DP,

United Kingdom Oxford University Press is a department of the University of Oxford

It furthers the University’s objective of excellence in research, scholarship, and education by publishing worldwide Oxford is a registered trade mark of Oxford University Press in the UK and in certain other countries

© Tadashi Okuyama and Howard Maskill 2014 The moral rights of the authors have been asserted

Impression: 1 Japanese version published by Maruzen Publishing Co., Ltd., Japan

© Tadashi Okuyama 2008

All rights reserved No part of this publication may be reproduced, stored in

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British Library Cataloguing in Publication Data

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1

Organic chemistry deals with the structures, synthesis, and functions of compounds whose molecules now include assemblies up to giant biomolecules such as nucleic acids, proteins, and polysaccharides Because so many life processes are regulated by interactions between small organic molecules and gigan-tic biomolecules, James Watson, the 1962 Nobel Laureate in Physiology and Medicine, was able to say

‘Life is simply a matter of chemistry’ It follows that organic chemistry applied to biological science is the basis of life science Current organic chemistry is also central to burgeoning new areas of materials sci-ence whose applications extend to industrial products which support our daily lives And, just as organic chemistry continues to develop, the way in which it is taught must adapt and, especially, use all the aids presently available to support the learning process

By developing an appreciation of how organic reactions take place based on orbital interactions and electron fl ow, this book allows known reactions to be understood and new ones to be predicted The book

is organized in a manner which will facilitate the transition from high school chemistry to university level organic chemistry, and provides insights into some currently developing areas In particular, the authors clearly present underlying principles and show how these bring order and logic to the subject

Ryoji Noyori, 2013

Foreword

Organic chemistry is a mature branch of science which continues to expand in the sense that new tions and new compounds continue to be discovered Some compounds newly isolated from natural sources support life; others, synthesized in the laboratory, are unknown in nature but have led to advances

reac-in medicreac-ine and other areas of science and technology A consequence of the huge and reac-increasreac-ing number

of known organic compounds is that any chemist can have book-knowledge of only a tiny fraction and practical experience of an even smaller number However, a molecule of an organic compound may gen-erally be seen as a functional group bonded to a hydrocarbon residue and organic chemistry is essentially the chemistry of a relatively small number of functional groups Consequently, comprehension of organic chemistry as a whole is achievable from knowledge of the characteristic reactions of functional groups and an understanding of how they occur, i.e their mechanisms

The Approach of this Book

There are different approaches to the teaching of organic chemistry at university level In this book, we begin with a review of atomic and molecular structure and then look at factors which determine the shapes of molecules Next, we cover acid–base (proton transfer) reactions since these are distinctive features of many reactions of organic compounds, especially ones of biological importance including reactions catalysed by enzymes We then show that all overall reactions of organic compounds belong to one of a relatively small number of classes of reaction types Moreover, when we introduce the concept of mechanism in organic chemistry, and look at how reactions take place, we see that only a small number

of types of elementary steps are involved

When features common to all organic reactions have been covered, we proceed to look at reactions of individual functional groups Our approach, based upon a survey of teachers of organic chemistry in over

50 colleges and universities in Japan and guided by nine reviewers from different parts of Europe and North America, is to focus on underlying mechanistic principles as the unifying basis of organic chemis-try The outcome is a concise non-mathematical text which introduces molecular orbital considerations early on and uses ‘curly arrows’ (as appropriate) to describe mechanisms throughout The book is not intended to be an encyclopaedic reference text of organic chemistry; it is a learning-and-teaching text and the coverage broadly corresponds to the organic chemistry syllabus of a typical honours degree in chemistry at a British university However, we include connections to biological sciences wherever they are relevant to emphasize that organic chemistry is the basis of life science To supplement the core chem-istry, we have also included ‘panels’ containing material (sometimes topical) which relate the chemistry

to current everyday life and biological phenomena Consequently, depending on the level to which the subject is to be taught, the book could be appropriate for students of health sciences and technology, as well as premedical students

Learning from this Book

To assist students, worked examples and exercises are embedded within each chapter; answers to chapter exercises are provided on the book’s web site, which we describe further below Each chapter also has a summary together with additional problems at the end In addition, we include an early section on organic nomenclature, appendices which contain reference data, and fl ow charts encapsulating reactions and interconversions of functional groups, and a comprehensive index

Preface

• Answers to in-chapter exercises

• 3D-rotatable models of numerous compounds featured in the book

• Multiple-choice questions for each chapter to help you check your understanding of topics you have

learned

For lecturers:

• Figures from the book in electronic format

• Answers to end-of-chapter problems

• Examples of organic synthesis reactions, related to topics covered in the book, for use in teaching

• Additional problems (with answers), to supplement those included in the book

To fi nd out more, go to www.oxfordtextbooks.co.uk/orc/okuyama/

You can also explore organic reaction mechanisms at www.chemtube3d.com This site provides a wide

range of interactive 3D animations of some of the most important organic reactions you are likely to

encounter during your studies

Acknowledgements

This book is based on the Japanese text, Organic Chemistry (Maruzen Publishing Co., Ltd., Tokyo, 2008)

by a group of authors including one of us We are very grateful to the other coauthors of that book,

especially Professors Mao Minoura and Hiroshi Yamataka (Rikkyo University), Akihiko Ishii (Saitama

University), and Takashi Sugimura (University of Hyogo), for their help during our work on this book

We are also grateful to Dr Ryohei Kishi (Osaka University) for his assistance in the preparation of some of

the molecular orbital diagrams, and to the editorial staff at OUP, especially Jonathan Crowe In spite of all

the help we have received, there will be residual errors in a book of this length; we welcome assistance

in rooting out mistakes of any sort and will post corrections on the above mentioned website Finally, we

acknowledge with appreciation that this book could not have been completed without the forbearance

and support of our wives

Some students occasionally fi nd organic chemistry a formidable subject involving the memorization of

an overwhelming number of compounds and their reactions However, as we mention in the preface, organic compounds fall into a small number of classes characterized by the functional groups at which reactions take place; similarly, there is only a limited number of reaction types classifi ed according to their mechanisms Consequently, systematic learning of relatively few mechanisms brings order and logic to organic chemistry, and will allow you to appreciate the subject in all its glorious and fascinating

diversity This text, Organic Chemistry: a mechanistic approach , has been written to guide you along

this path

An organic chemical reaction—the transformation of one compound into another—is described in

terms of the structures of compounds involved, and the reactivity of a compound (how it reacts and

whether the reaction will be fast or slow) is determined by its structure (and the reaction conditions) How a reaction is believed to occur, i.e its reaction mechanism, is nowadays represented by curly arrows describing the movement of electrons, and we use mechanistic schemes throughout this book Usually,

the schemes will show not just how the reaction occurs but why it occurs in the way shown, and why it

is favourable Our pictorial reaction schemes with structures of compounds and curly arrows showing how they react contain a lot of information We have used several devices to assist their interpretation, including colour and annotations

The following two schemes taken from the text illustrate some conventions in this book to describe reaction mechanisms Some boxes contain text to indicate what facilitates a particular step, i.e why it

is favourable, and bonds newly formed in each step; text in other boxes identifi es types of groups, e.g

nucleophile or electrophile Coloured text under reaction arrows identifi es the type of reaction which may be a single step (e.g proton transfer) or an overall transformation (e.g substitution) Text under a chemical species indicates its nature, e.g an intermediate Note that all steps in these two schemes are reversible in principle but, by including one arrow in the fi nal step of the second scheme in parentheses, for example, we identify a step as being essentially unidirectional because of the reaction conditions and/

or the equilibrium constant

O H

H R

O OR'

H H

H O H

leaving group

nucleophile

new bond

driving force (electron pull)

A Note to Students ix

It is important that you can draw clearly in two dimensions organic structures which are generally

three-dimensional To do this, practice with pencil and paper is essential In addition, you have to learn

to use curly arrows to describe the movement of electrons corresponding to a reaction, i.e bond breaking

and bond making steps Remember that organic chemistry can be communicated by drawing structures

of molecules and curly arrow reaction mechanisms—it is as though we have a language with structures

and mechanisms as the vocabulary and grammar; and, as with learning a language, fl uency develops with

practice

Worked examples are embedded in the text to review what has just been covered and illustrate how to

solve exercises and problems within and at the ends of chapters, respectively In later chapters, we also

have ‘supplementary problems’ which are a little more diffi cult and may relate to material in previous

chapters It will be most benefi cial if you attempt exercises and problems without looking at the solutions

fi rst, even though they are available on the website associated with the book If you fi nd that you cannot

do an exercise or problem, go back to the text to review the material upon which the exercise or problem

is based, then try again This iterative process is an important aspect of learning organic chemistry and

will help you to learn how to solve problems generally (rather than just memorize facts) When you arrive

at a reasonable answer, check it against the solution provided However, note that there may be different

ways of approaching some problems (and some may have more than a single correct answer); but when

you are really stuck, always seek advice

One fi nal point: the names of chemists crop up from time to time throughout the book; they are usually

eminent chemists who have made signifi cant contributions to organic chemistry (which is, after all, an

area of human endeavour) and their portraits are shown Sometimes, reactions have been named after

them Although the use of chemists’ names is a long-standing and often helpful short-hand way of

refer-ring to reactions and well-established empirical rules or general principles, knowing and understanding

the chemistry involved is more important than remembering the names

ATP adenosine triphosphate

BHA butylated hydroxyanisole

DMSO dimethyl sulfoxide

DNA deoxyribonucleic acid

DOMO doubly occupied molecular orbital

E.A electron affi nity

EWG electron-withdrawing group

FGI functional group interconversion

Fmoc fl uorenylmethoxycarbonyl

GC gas chromatography

HOMO highest occupied molecular orbital

HPLC high performance liquid

LDA lithium diisopropylamide

LUMO lowest unoccupied molecular orbital

MCPBA m -chloroperoxybenzoic acid

Me methyl

MO molecular orbital

mp melting point

MS mass spectrometry

NAD + nicotinamide adenine dinucleotide

NADH reduced form of NAD

NBS N -bromosuccinimide

n.g.p neighbouring group participation

NMF N- methylformamide

NMR nuclear magnetic resonance

NOE nuclear Overhauser effect

O.P optical purity

S N 2 bimolecular nucleophilic substitution

S N i nucleophilic substitution, internal

SOMO singly occupied molecular orbital

VSEPR valence shell electron pair repulsion

Foreword v

Chapter 1 Atoms, Molecules, and Chemical Bonding—a Review 1

Chapter 2 Molecular Structure and Shapes of Organic Molecules 22

Chapter 3 Organic Compounds: their Functional Groups, Intermolecular

Chapter 4 Conformation and Strain in Molecules 71

Chapter 5 Conjugation, π-Electron Delocalization, and Aromaticity 89

Chapter 7 Organic Reactions and the Concept of Mechanism 138

Chapter 8 Nucleophilic Addition to the Carbonyl Group in Aldehydes and Ketones 165

Chapter 9 Nucleophilic Substitution Reactions of Carboxylic Acid Derivatives 188

Chapter 10 Reactions of Carbonyl Compounds with Hydride Donors and

Chapter 11 Stereochemistry and Molecular Chirality 225

Chapter 12 Nucleophilic Substitution Reactions of Haloalkanes

Chapter 13 Elimination Reactions of Haloalkanes and Related Compounds 273

Chapter 14 Reactions of Alcohols, Ethers, Thiols, Sulfi des, and Amines 289

Chapter 15 Addition Reactions of Alkenes and Alkynes 314

Chapter 16 Electrophilic Aromatic Substitution 341

Chapter 17 Enolate Ions, their Equivalents, and Reactions 373

Chapter 18 Reactions of Nucleophiles with Alkenes and Aromatic Compounds 402

Chapter 19 Polycyclic and Heterocyclic Aromatic Compounds 423

Chapter 20 Reactions involving Radicals 444

Overview of Contents

xii Overview of Contents

Chapter 21 Pericyclic Reactions: Cycloadditions, Electrocyclic Reactions,

Chapter 22 Rearrangement Reactions involving Polar Molecules and Ions 490

Chapter 24 Chemistry of Biomolecules 528

Chapter 25 Structural Determination of Organic Compounds 561

Foreword v

Chapter 1 Atoms, Molecules, and Chemical Bonding—a Review 1

Chapter 2 Molecular Structure and Shapes of Organic Molecules 22

Contents in Detail

xiv Contents in Detail

Chapter 3 Organic Compounds: their Functional Groups,

3.9 Intermolecular Interactions and Physical Properties of Organic Compounds 61

Chapter 4 Conformation and Strain in Molecules 71

Contents in Detail xv

Chapter 5 Conjugation, π-Electron Delocalization, and Aromaticity 89

5.7.1 Interactions of organic molecules with electromagnetic radiation 104

6.2.3 Acidity of aqueous solutions and ratios of conjugate acid–base pairs 117

xvi Contents in Detail

Chapter 7 Organic Reactions and the Concept of Mechanism 138

7.2.3 Concerted bond formation and cleavage in an elementary reaction 143

7.4.2 From reaction of a single molecule to reaction on a molar scale 150

Panel 7.1 Reaction profi les for unimolecular bond-cleavage elementary reactions 151

7.5 Characterization of Organic Reactions and Investigation of their Mechanisms 156

7.5.4 Effect of substrate structure and reaction conditions on rate constants 160

Chapter 8 Nucleophilic Addition to the Carbonyl Group in Aldehydes and Ketones 165

Panel 8.1 Common carbonyl compounds: methanal, ethanal, and propanone 168

8.3.2 The mechanism of hydration of carbonyl compounds and catalysis 173

Contents in Detail xvii

Chapter 9 Nucleophilic Substitution Reactions of Carboxylic Acid Derivatives 188

9.4.3 Comparison of reactions of nucleophiles with carboxylic acid derivatives

xviii Contents in Detail

11.3 The Fischer Convention for representing the Confi guration of Chirality Centres 232

Chapter 12 Nucleophilic Substitution Reactions of Haloalkanes

Panel 12.3 The S N 1 mechanism in biological substitution reactions 265

12.5 Intramolecular Nucleophilic Displacement: Neighbouring Group Participation 266

Contents in Detail xix

Chapter 13 Elimination Reactions of Haloalkanes and Related Compounds 273

13.3 The E1cB Elimination Mechanism and Graded Transition Structures

Chapter 14 Reactions of Alcohols, Ethers, Thiols, Sulfi des, and Amines 289

Panel 14.6 Fluorodeoxyglucose in cancer diagnosis: rapid synthesis by an S N 2

xx Contents in Detail

Chapter 15 Addition Reactions of Alkenes and Alkynes 314

Chapter 16 Electrophilic Aromatic Substitution 341

16.2 Electrophilic Aromatic Substitution by an Addition–Elimination Mechanism 342

16.4.1 Activating and deactivating substituents in electrophilic aromatic substitution 349

16.4.2 Effects of substituents on the stability of the benzenium ion 350

Contents in Detail xxi

16.7.5 Control of reactivity and regioselectivity in syntheses of

17.8.2 Synthesis of ketones and carboxylic acid via enolates

Chapter 18 Reactions of Nucleophiles with Alkenes and Aromatic Compounds 402

xxii Contents in Detail

18.1.2 Kinetic and thermodynamic control of carbonyl and conjugate additions 406

18.1.3 Addition of organometallic reagents and metal hydrides to

Panel 18.1 Cyanoacrylate esters in instant glues, for the detection of fi ngerprints,

18.4 Conjugate Addition of Enolate Ions to α, β-Unsaturated Carbonyl Compounds 410

18.6 Nucleophilic Aromatic Substitution by the Addition–Elimination Mechanism 412

18.7 Nucleophilic Aromatic Substitution by the Elimination–Addition Mechanism 414

Chapter 19 Polycyclic and Heterocyclic Aromatic Compounds 423

Panel 19.2 Carcinogenicity of polycyclic aromatic compounds: epoxide intermediates

19.3 Acid–Base Properties of Heteroaromatic Compounds containing Nitrogen Atoms 430

Contents in Detail xxiii

20.9 Formation of Radical Ions by Single Electron Transfer and their Reactions 461

20.9.2 One-electron reduction of carbonyl compounds and radical coupling 463

Chapter 21 Pericyclic Reactions: Cycloadditions, Electrocyclic Reactions,

Chapter 22 Rearrangement Reactions involving Polar Molecules and Ions 490

22.2 Concerted 1,2-Shifts bypassing the Formation of Unstable Carbenium Ions 493

xxiv Contents in Detail

Panel 23.1 Recent C–C bond-forming reactions using catalytic organometallic complexes 507

23.2.2 Exploiting functional group interconversions: synthesis of a

23.2.4 Multiple functionalities which lead to standard disconnections 513

Chapter 25 Structural Determination of Organic Compounds 561

25.6.3 High-resolution mass spectrometry: determination of molecular formulas 598

Symbols and Recommended Values of Some Physical Constants / Unit Conversions 617

Fundamental Classes of Reactions and Guidelines for Writing Curly Arrows 618

Common madder ( Rubia

tinctorum ).

(This fi le is licensed under

the Creative Commons

Attribution-Share Alike 3.0

Unported license.)

Bolinus brandaris

(This fi le is licensed under

the Creative Commons

In contrast, inorganic compounds are normally very stable, generally crystalline, and not usually combustible The difference between organic and inorganic compounds was originally ascribed to an unexplainable, almost mystical, ‘vital force’ which was consid-ered to be inherent in the compounds obtained from living sources, and this concept of

‘vitalism’ survived almost until the middle of the nineteenth century

Pigments

In ancient times, clothing was made from fi bres obtained from plants or animals and was dyed with pigments extracted from plants, e.g blue indigo and red alizarin Tyrian purple is the colour and the name of the prestigious dye used for liturgical vestments and the robes of royalty; it was produced from sea snails in eastern Mediterranean countries

in extremely low yield (hence its costliness)

Prologue

The History and Scope of Organic Chemistry

indigo (blue, from plants

in the genus Indigofera)

H

O N

O

H

O N O

Br

the main ingradient of Tyrianpurple

(from Bolinus brandaris, a type of sea snail)

O

O

OH OH

alizarin (red,from the roots of madder)

Medicines and toxins

Some medicines originally discovered in natural products long ago are still used today Cinchona bark was used as a folk medicine by natives of South America to relieve pain and reduce fevers, and was brought to Europe by Jesuits in the sixteenth century The

Prologue xxvii

main ingredient was later found to be quinine and is used to treat malaria (and as a

bitter-tasting ingredient of some cocktails, e.g gin and tonic)

Aspirin is an example of a compound developed from the use of plants for medical

care In ancient Greece, the bark of willow trees was used to relieve pain, and the active

ingredient was later found to be salicin, which is a glucose derivative of salicyl alcohol

Testing modifi cations of this compound led chemists working for Bayer AG in Germany

to acetylsalicylic acid in 1897 This fi rst synthetic drug was marketed in 1899 as aspirin

and is still commonly used as a pain-relieving, fever-reducing, and anti-infl ammatory

agent; it is also used in the treatment and prevention of heart attack, stroke, and blood

clot formation owing to its anti-platelet forming properties

N

H H

HOH 2 C

O O HO

O

CH 3 C O OH

Poisonous substances from plants are also known: coniine is found in the extract from

hemlock ( Conium maculatum ), which was used to poison Socrates in 399 BC

In suitably reduced amounts, some poisonous substances act as medical drugs

Digoxin, for example, may be extracted from foxgloves ( Digitalis ) and used for the

treat-ment of various heart conditions

O O

O O

OH

OH H

H OH

Antibiotics are a relatively new type of drug produced by microorganisms In 1928,

the Scottish biologist Alexander Fleming working in London discovered a substance

produced by a mould which killed staphylococcus bacteria He named the substance

penicillin and it is used for the treatment of bacterial infections; the term is now used

generically for structurally related compounds Streptomycin is another type of

antibi-otic which was the fi rst effective drug for tuberculosis (TB) This was originally isolated

in 1943 in the USA in the laboratory of S Waksman who coined the term antibiotics

(substances produced by microorganisms which kill other microorganisms, principally

bacteria) Further antibiotics have subsequently been discovered and are widely used as

antibacterial drugs

Chinchona tree.

(Courtesy of Forest and Kim Starr This fi le is licensed under the Creative Commons Attribution-Share Alike 3.0 Unported license.)

Foxglove.

(Photograph by Varda-Elentari.)

xxviii Prologue

Friedrich Wöhler

(1800–1882)

Wöhler studied chemistry

under the Swedish

chemist, Jakob Berzelius

in Stockholm, and taught

chemistry in Berlin and

later in Göttingen He also

principally for his work

on the electrolysis of salts

of carboxylic acids (Kolbe

electrolysis, Chapter 20)

and the synthesis of

salicylic acid (Kolbe–

RCNH

CO 2 H O

H

O H

CH 3 N H

The Development of Organic Chemistry

as a Science The end of ‘vitalism’

As mentioned above, chemists at the beginning of the nineteenth century believed that organic compounds found in nature could not be prepared in the laboratory—they could only be formed by living organisms However, in 1828, Friedrich Wöhler discovered that urea, an organic compound found in urine, is formed when an aqueous solution of an inorganic salt, ammonium cyanate, was evaporated to dryness

t a a c m u i n m

Subsequently in 1844, Hermann Kolbe showed that ethanoic (acetic) acid could be pared from carbon disulfi de, which was known to be obtainable from iron pyrites (FeS 2 ) and graphite (a form of carbon)

CS 2 CH 3 CO 2 H FeS 2 + C

ethanoic acid (acetic acid) carbon disulfide

These fi ndings by Wöhler and Kolbe established that the concept of ‘vitalism’ in chem-istry was no longer credible—organic compounds could be prepared in the laboratory—but its demise was not instantaneous and it lingered on in other areas of science However, the development of modern organic chemistry had begun

Concept of ‘radical’ and the school of organic chemistry in Giessen

It was recognized by 1830 that there were different compounds with the same

composi-tion; we know these as isomers and Wöhler’s ammonium cyanate and urea are examples

This implied that the atoms of a pair of organic isomers were connected together ently A collaboration in the 1830s between Wöhler and another important chemist of the time, Justus von Liebig, led to the concept of ‘radicals’—groups of atoms joined together

differ-Prologue xxix

which occurred in different organic compounds These ‘radicals’ were forerunners of

what we now call groups (e.g the ethyl group) in organic chemistry; it was thought that

complex organic molecules were composed of radicals in the way that simple molecules

are composed of atoms

At the time, Liebig had been a Professor at the University of Giessen since 1824 He

had improved analytical and experimental methods of organic chemistry in the 1820s

and 1830s and built up a teaching and research school His innovative methods of

chemistry teaching and research in Giessen laid the foundation for the further

develop-ment of organic chemistry, and provided a model for academic chemistry elsewhere

His school attracted many students who later became renowned in the fi eld of organic

chemistry: they include Hofmann, Kekulé, and Williamson, who are mentioned

else-where in this book

Early modern history of organic chemistry

The concept of valence developed following the mid-decades of the nineteenth

cen-tury, and August Kekulé and Archibald Couper independently proposed the

tetrava-lency of carbon atoms in 1858 Kekulé also pointed out the possibility of cyclic

structures of carbon compounds and proposed a six-membered ring structure for

ben-zene in 1865 (Panel 5.1, p 100) At that stage, only two-dimensional molecular

struc-tures were considered

In 1874, Jacobus van’t Hoff and Joseph Le Bel independently proposed tetrahedral

bonding of carbon atoms (Chapter 2) to account for the optical activity of some carbon

compounds and the enantiomers of tartaric acid which had been discovered by Louis

Pasteur (Panel 11.4, p 242) in 1848 The tetrahedral model of carbon bonding was

sup-ported by the carbohydrate studies of Emil Fischer (Panel 11.3, p 238), and led towards

an appreciation of three-dimensional (stereochemical) structures of organic compounds

By the late nineteenth century, a comprehensive approach to organic chemistry based

on structures of compounds had been established, and new organic reactions were

increasingly being discovered; some of those reactions are still known by the names of

their discoverers and examples will be discussed in this book During this time and in

the early years of the twentieth century, the accumulating knowledge of structures and

reactions of organic compounds were being systematically organized to establish what

we might call ‘classical’ organic chemistry

Modern concepts and theories of chemical bonding

and organic reactions

Following developments in physics on atomic structure at the beginning of the twentieth

century, Gilbert Lewis (Chapter 1) and Irving Langmuir in the United States proposed

the octet rule and the concept of covalent bonding in 1919 Quantum mechanics was

established in the 1920s and provided the basis of modern theories of chemical bonding

In the 1930s, Linus Pauling introduced concepts such as electronegativity,

hybridi-zation, and resonance which proved very useful in organic chemistry (Panel 2.1,

p.  28) as will be discussed in Chapters 1 and 2 About this time, notions of how

organic reactions occurred (mechanisms of organic reactions) were being developed

based on contemporary electronic theories of chemical bonding R Robinson and

C.K Ingold, for example, described organic reactions in terms of the breaking and

forming of chemical bonds involving the movement of electrons (Chapters 7 and 12)

Although their representation of reactions was qualitative, it has developed into a

simple and useful pencil-and-paper method of describing organic chemical

reac-tions, and organic reactivity

Justus von Liebig (1803–1873)

Reproduced from Duyckinick, Evert A

Portrait Gallery of Eminent

Men and Women in Europe and America New

York: Johnson, Wilson & Company, 1873

xxx Prologue

Quantum mechanics was applied to chemical bonding theory following its tion in mathematical physics, but the application to organic compounds came later because of the huge computations which were required In 1931, Erich Hückel intro-duced some simplifying approximations to molecular orbital theory which enabled the computation of energies of π electron systems of organic molecules (Chapter 5) These

introduc-descriptions of ground and excited states of organic molecules were subsequently extended into the area of organic reactions when, in 1952, Kenichi Fukui proposed

frontier orbital theory to describe organic reactivity (Chapter 7) Owing to ments in high-speed computers and ever-improving computational methodologies, we can now reliably analyse a wide range of chemical phenomena based, ultimately, on quantum mechanics

Chemical industry

Organic chemistry has always been applied by industry to improve the quality of life The fi rst major chemical industries developed for the production of synthetic dyestuffs

in the UK and Germany These followed the serendipitous discovery in 1856 of a dye in

a reaction of impure aniline by the British chemist, W.H Perkin; it gave a delicate shade

of purple and Perkin marketed it as aniline purple or mauve (later, it was also called mauveine )

A component of mauve (a synthetic purple dye)

Synthetic complexity as a measure of progress

in organic chemistry

The increasing complexity of compounds synthesized can be seen in the work of one

of the most celebrated synthetic chemists of the twentieth century, the American, R.B Woodward His syntheses of natural products including quinine (1944, see above), cho-lesterol (1952), chlorophyll (1960), and (jointly with the Swiss, A Eschenmoser) vitamin

B 12 (1972) inspired many by their originality

aniline purple when he was

only 18 His business was

so successful that he was

able to retire as a wealthy

man at the age of 36

After that, he devoted the

rest of his life to organic

chemistry investigations

in his private laboratory

The Perkin reaction for the

Carothers worked for Du

Pont and also contributed

to the development of

neoprene, a synthetic

rubber

Prologue xxxi

N N

NH 2 O

NH 2 O

NH 2 O

N N Co CN H

O NH 2

H 2 N O

H 2 N O

HN O

O P O

O

N N HO

– O O HO

N Mg

O

O O

OCH 3 O

chlorophyll a

The increasing stereochemical complexity (as well as the size of molecules) has been a

feature of compounds synthesized in the twenty-fi rst century Perhaps one of the most

diffi cult so far is ciguatoxin (M Hirama, 2001) with a molecular formula C 60 H 86 O 19 and

33 chirality centres, which is found in fi sh in tropical waters and causes a type of fatal

food poisoning called ciguatera

O O

O

O O

O O

O O

O

O O O

OH

CH 3

CH 3

H H OH

CH 3 H

H H

H

H H

Organic Chemistry: Now and in the Future

Organic chemistry can trace its scientifi c origins back to the enlightenment in Europe, so

is a relatively mature science, and continuous progress has led to developments which

now support our daily lives in countless ways Synthetic fi bres and dyes for clothing,

agricultural chemicals and fertilizers, plastics, paint, and adhesives, for example, are all

industrial products based on conventional organic chemistry Following the

exploita-tion of the properties of liquid crystals for displays, for example, at the interface with

physics, we are currently witnessing major developments in the formulation of further

new organic materials (e.g semiconductors, photovoltaic compounds, compounds

which show electroluminescence, and single molecules which function as electronic

components) Ongoing progress in the prevention and cure of diseases benefi ts from the

Robert Burns Woodward (1917–1979)

Woodward was a professor

at Harvard University and was awarded the 1965 Nobel Prize in Chemistry for his outstanding achievements in organic synthesis In addition

to his achievements in synthesis, his collaboration with the theoretician,

R Hoffmann, led to the widespread appreciation of the importance of orbital symmetry considerations

in concerted reactions (Chapter 21)

xxxii Prologue

contributions of organic chemistry to life sciences (e.g the investigation of the molecular basis of diseases and the ongoing discovery of new pharmaceutical compounds) Although the organic chemical industry unquestionably produces compounds and materials now deemed essential for civilized life, progress has occasionally been accom-panied by adverse side-effects By-products of unregulated industrial chemistry and irresponsible disposal of chemical wastes pollute our environment, and unanticipated medicinal hazards occasionally compromise well-intentioned use of pharmaceutical compounds Some of these harmful aspects of industrial and medicinal applications of organic chemistry are because of our incomplete understanding of details of the chemis-try involved, and addressing such matters is an ongoing task for chemists

A more environmentally benign chemical industry, increased use of renewable energy, and more effi cient use of carbon resources (including better recycling of materials) are major issues in the twenty-fi rst century in which organic chemists will surely be engaged Impossible to predict, however, are the applications of compounds yet to be discovered

in the curiosity-led investigations of organic chemists

1.1 The Electronic Structure of Atoms

At the beginning of any study of chemistry, we learn that compounds are built up from

atoms, that a single atom consists of a nucleus and surrounding electrons, and that the

nucleus consists of protons and neutrons

An element is uniquely identifi ed by its atomic number ( Z ), which is the number of

protons in the nucleus (the magnitude of its positive charge) and equal to the number of

electrons around the nucleus of a (neutral) atom of the element If it is needed, Z is given

as a lower prefi x to the chemical symbol of an element; see Figure 1.1 As indicated

1

Organic chemistry deals with the compounds of carbon and is a major part of the wider subject There are hugely more compounds of carbon than of all other elements combined Why is this so? The answer must lie in the special properties of the element, and the characteristics of the carbon atom Carbon

is in the middle of the second period of the periodic table of elements; its atoms form strong bonds both to other carbon atoms and to atoms of other elements As a result, more than ten million carbon compounds are known, and more remain to be discovered Properties of chemical bonds between atoms within molecules, of individual molecules themselves, and of organic compounds and materials which

we encounter as bulk material, are all ultimately dependent on the electronic structures of the atoms involved We begin our study of organic chemistry by reviewing the nature of atoms and, in particular, their electronic structures This will lead on naturally to a basic description of chemical bonds in simple molecules which, in subsequent chapters, we shall be able to develop to a level suffi cient to account for the wide-ranging reactivities of organic compounds

• Lewis representations of atoms

• Ionic and covalent bonds

• Electronegativity and bond polarity

• Lewis structures of simple molecules and ions

• Introduction to resonance

2 1 Atoms, Molecules, and Chemical Bonding—a Review

above, the nucleus of an atom of a specifi ed element has neutrons in addition to protons,

and the sum of the number of protons and neutrons in the nucleus is the mass number

( A ); this is indicated as an upper prefi x to the chemical symbol of the element if it is

needed

The forms of an element with different numbers of neutrons in the nucleus are called

isotopes, and they are chemically equivalent; they have the same value for Z but different

values for A Isotopes exist in proportions (natural abundances) which vary only slightly

according to the distribution of the element in nature

Masses of atoms are exceedingly small and commonly expressed in atomic mass units (1 amu ≈ 1.66 × 10 −27 kg) More conveniently, however, an atomic mass is usually

expressed as its relative atomic mass ( A r ), the standard being the mass of one atom of a specifi c isotope of a specifi c element; the modern standard is the 12 C isotope of carbon whose mass is defi ned as 12.0000 amu Normally, however, we are not dealing with iso-topically pure elements, but with the mixtures which occur in nature Consequently, the relative atomic mass of an element (as opposed to that of just one of its isotopes) is the

weighted mean of the values of A r of the naturally occurring isotopes For 13 C, the less

common stable isotope of carbon whose natural abundance is about 1.11%, A r = 13.0034, and the value for the element carbon is 12.011

How many protons and neutrons do nuclei of the following atoms have?

(a) B115 (b) Na11 (c) N147 (d) F199

Exercise 1.1

How many protons and neutrons does the nucleus of an atom of each of the following isotopes

of carbon have: 126C , 136C , and 146C ? ( 146C is a radioactive isotope, a radioisotope, of carbon used for carbon dating: see Panel 1.1.)

Exercise 1.2

The relative atomic mass of

an element is sometimes

called its atomic weight

Some elements, including

fl uorine ( 19 F) and sodium

( 23 Na), occur naturally as

single stable isotopes

1.1.2 Electrons and atomic orbitals

According to quantum theory, the energy of an electron outside the nucleus of an atom

cannot be continuously variable—it is quantized —and only certain energy levels, which

are called atomic orbitals (AOs), are available to the electron In addition to being an

energy level, an AO has spatial character which is identifi ed by letters of the Roman alphabet, s, p, d, and f (an s orbital, for example, is spherical) In other words, an AO restricts the space available to an electron in an atom in addition to limiting its energy

An electron is characterized by spin as well as by its energy and spatial properties

This is a property which originates in quantum theory and can have only one of two possible values It does not matter whether we call these values plus and minus, left and

right, or up and down (we cannot attach a simple physical signifi cance to spin ) Any AO

can accommodate a single electron of either spin, or two electrons if they are of opposite

spin (when they are said to be spin-paired )

Atomic orbitals available to the electrons around the nucleus of an atom are grouped into shells of increasing energy according to their principal quantum number ,

n (1, 2, 3, …); n also determines the types and number of orbitals within the shell The shell of lowest energy with n = 1 has only a single s orbital, labelled 1s, so it can contain

only two electrons The next shell ( n = 2) also contains an s orbital (labelled 2s) and, in addition, three p orbitals (2p x , 2p y , and 2p z ); these three are degenerate —they are of the

Atomic orbitals involved in

1.1 The Electronic Structure of Atoms 3

The radioisotope 14 C is produced in the upper layers of the atmosphere by the nuclear reaction of thermal neutrons

(produced by cosmic rays) with nitrogen 14 N

14N + n (neutron)1 → 14C + H1

It then reacts rapidly with oxygen to form radioactive carbon dioxide which becomes distributed throughout the

atmosphere mixed with 12 C carbon dioxide

The 14 C radioisotope undergoes decay by emission of an electron to give the stable 14 N isotope of nitrogen with a

half-life of about 5730 years (one half of the 14 C decays every 5730 years)

14C→ 14N + e−

The balance between its formation and decay leads to a stationary state natural abundance of 14 C in atmospheric

carbon dioxide of about one part in one trillion (∼1 : 10 12 ) Atmospheric carbon dioxide is absorbed in plants by

pho-tosynthesis (this process is called the fi xation of CO 2 ) and the carbon is transferred to animals which consume plants as

food Consequently, as long as CO 2 from the atmosphere is being incorporated, the 14 C/ 12 C ratio within a living system

will remain constant Once the fi xation stops, however, and the radioactive decay of 14 C continues, the 14 C/ 12 C ratio in

the fi xed carbon decreases with time As we know the half-life of 14 C, analysis of the radioactivity of organic

materi-als of bioorganic origin enables us to estimate the time since the carbon dioxide was fi xed This technique is called

radiocarbon dating , or simply carbon dating, and was developed in 1949 by Willard Libby (University of Chicago) who

was awarded the Nobel Prize in Chemistry in 1960 for the work Times of up to about 60 000 years can be estimated

and the method is widely applied in archaeology Libby and his team fi rst demonstrated the accuracy of the method

by showing that the age of wood from an ancient Egyptian royal barge estimated by radiocarbon dating agreed with

the age of the barge known from historical records

Panel 1.1 Radiocarbon dating

same energy The four AOs of this second shell ( n = 2) can accommodate a total of up to

eight electrons The third shell ( n = 3) contains one 3s and three 3p orbitals (3p x , 3p y ,

and 3p z ) plus a set of fi ve degenerate 3d orbitals—a total of 9 AOs which (together) can

hold up to 18 electrons

The relative energies of some of the atomic orbitals mentioned above for an

unspeci-fi ed atom are shown in Figure 1.2 The s orbitals of increasing energy with principal

quantum numbers 1–5 are shown in the column on the left; in the centre column, the

p orbitals are seen to increase in energy starting from n = 2; the fi ve degenerate d orbitals

only start with n = 3 (and no higher ones are shown) None of the seven-fold degenerate

f orbitals are shown as they are higher in energy and do not start until n = 4; they are of

minimal importance in organic chemistry

1s 2s 3s 4s

2p 3p

3d 4p

4 1 Atoms, Molecules, and Chemical Bonding—a Review

As mentioned above, the atomic orbital occupied by an electron indicates the space available to it as well as its energy An s orbital is spherical, while each p orbital is elongated and circularly symmetrical about one of the three mutually perpendicular Cartesian axes (so they are labelled p x , p y , and p z ), as illustrated in Figure 1.3 (see also Sub-section 2.2.1)

1.1.3 Electronic confi guration of an atom

The number of electrons around the nucleus of an isolated neutral atom is determined

by its atomic number ( Z , equal to the number of protons in its nucleus) In principle,

these electrons can be distributed amongst the atomic orbitals in many ways, and any

one distribution is referred to as an electronic confi guration (or electronic structure ) The

different confi gurations correspond to different total electronic energies, and the most

important is the one of lowest energy; this is called the ground-state electronic confi

gu-ration We can imagine a nucleus of an atom and a number of electrons equal to its atomic

number being fed into the available orbitals; this is done according to the following three

rules (sometimes known collectively as the Aufbau Principle from the German word

meaning ‘building up’):

(1) Electrons are added to orbitals in the order of their increasing energy (see Figure  1.2 )

(2) Any orbital can hold one electron of either spin or two electrons of opposite spin

(3) When the next available orbitals are degenerate , electrons with the same spin

(i.e unpaired) are added to them one at a time until they are all singly occupied

( Hund's rule ); a second electron of opposite (or paired) spin may then be added to

each of them in turn

To give a specifi c example, the result of following these rules for carbon ( Z = 6, so there are

6 electrons to be fed in) leads to the ground-state electronic confi guration 1s 2 2s 2 2p x 1 2p 1 y shown in Figure 1.4

That an orbital cannot

contain two electrons of

the same spin is called the

Pauli exclusion principle

1s 2s

3s

2p 3p

z

(a)

x

y z

x y z

x y z

(b)

s

Figure 1.3 The shapes of s

and p atomic orbitals

1.1 The Electronic Structure of Atoms 5

Table 1.1 shows the ground-state electronic confi gurations of elements of the fi rst three

periods of the periodic table Orbital occupancy is shown by a suffi x (1 or 2) to the

orbital designation The fi rst column corresponds to the fi rst period with the addition

of electrons to the 1s orbital to give hydrogen fi rst then the noble gas element, helium

This completes the fi rst shell (1s 2 ) which then becomes the inner shell, abbreviated by

[He], for elements of the second period listed in the second column of Table 1.1 where

electrons are added to the second shell ( n = 2) Amongst these, for example, the electronic

confi guration of 6 C is given as [He]2s 2 2p 1 x 2p y 1 (see Figure 1.4 ); this shows that the ground

state of a C atom contains the fi lled inner shell of He ([He]), 2 electrons in the 2s orbital,

and 1 electron in each of 2p x and 2p y orbitals

The second shell is complete (two electrons in each of the four orbitals available) with

the electronic confi guration of neon The third column of Table 1.1 corresponds to

ele-ments of the third period where electrons are being added to the third shell ( n = 3), the

inner fi rst and second shells being complete; this period ends with the third noble gas

element, argon

Any two of the three 2p orbitals could contain an electron since they are degenerate; but if the electrons were spin paired

in just one of the three, i.e contrary to Hund's rule, the confi guration would not be the one of lowest energy The ground-state electronic confi guration of 6 C can be represented by [He]2s 2 2p 2 ,

it being understood that the two 2p electrons occupy different orbitals

Give the ground-state electronic confi guration of each of the following elements

(a) 35Br (b) 38Sr (c) 50 Sn

Exercise 1.3

We have already seen that an element is uniquely identifi ed by its atomic number ( Z )

which, in the neutral atom, is equal to the total number of electrons around the nucleus

However, it is the electrons in the outermost shell (the valence shell ) which characterize

the nature of the element, and these are called the valence electrons of the atom The

electrons of the full inner shells are called core electrons ; they have only a minor infl

u-ence on the chemical properties of the element and are not involved in the formation of

chemical bonds For example, lithium has one valence electron (2s 1 ), fl uorine has seven

(2s 2 2p 5 ), and carbon has four (2s 2 2p 2 ) in the n = 2 valence shell Atoms of these three

ele-ments have 1s 2 inner core electrons and, as for all elements, their chemical properties are

determined principally by their valence electrons

Following completion of the third period, the next two electrons enter the 4s orbital (potassium [Ne]3s 2 3p 6 4s 1 and calcium [Ne]3s 2 3p 6 4s 2 )

in the normal way As we saw in Figure 1.2 , however, the next lowest orbitals are the fi ve degenerate 3d orbitals, not the three 4p orbitals Filling these orbitals corresponds to the fi rst transition metals (d-block elements), Sc, Ti, V, etc

How many valence electrons does an atom of each of the following elements have?

(a) O (b) Cl (c) B (d) N (e) Mg

Exercise 1.4

Table 1.1

Ground-state electronic confi gurations of elements a

a The symbol of each element is given with its atomic number The fi lled inner shells of the second and third

period elements are indicated by the bracketed symbol of the last noble gas before the element, [He] or [Ne];

these are called the core electrons (see above)

6 1 Atoms, Molecules, and Chemical Bonding—a Review

Gilbert N Lewis

(1875–1946)

(Kindly supplied by Edward

Lewis.)

Lewis proposed what we

now call Lewis structures

to represent the number

of valence electrons of

atoms and ions, as well as

bonds in simple molecules

(see Section 1.3), and the

Lewis acid–base concept

or sharing electron(s) This concept is sometimes known as the octet rule Atoms on the

left side of the periodic table (metals) tend to lose one or more electrons to give positively charged ions (cations), e.g eqn 1.1 for lithium The outermost shell of an ion formed in this way was part of the core of the neutral atom, and the cation has the same electronic confi guration as an atom of the noble gas which precedes the metal in the periodic table

1.1.4 Lewis representation of atoms

In 1902, the American G.N Lewis proposed a method of representing atoms which gave prominence to their valence electrons and facilitated comparisons between different elements The Lewis representation of an atom is the normal chemical symbol of the element with valence electrons shown by dots, i.e the chemical symbol corresponds to the nucleus and the core electrons (those in the fi lled inner shells) Table 1.2 shows part

of the periodic table with Lewis representations of atoms

By comparing the Lewis representations with the ground-state electronic confi tions in Table 1.1 , we see that the four dots around the C for carbon correspond to two electrons in the 2s orbital and one electron in each of two 2p orbitals For the oxygen atom, two electrons in the 2s orbital and four electrons in 2p orbitals are represented

gura-by six dots around the O The maximum number of dots for the valence electrons of the

main group elements shown here (periods 1–3) is eight—an octet

Table 1.2 Lewis representations of atoms

Group no.

No of valence electrons

1 1

2 2

13 3

14 4

15 5

16 6

18 8

17 7 Period

1 Period 2 Period 3

1.2 Chemical Bonding 7

On the other hand, those elements on the right side of the periodic table (non-metals)

tend to achieve complete valence shell octets by gaining one or more electrons to give

negatively charged ions (anions), e.g eqn 1.2 for fl uorine The complete electronic

con-fi guration of the anion so formed is the same as that of an atom of the noble gas element

which follows the non-metal in the periodic table

Atoms can also achieve the noble gas electronic confi guration by sharing valence

elec-trons with other atoms, as will be discussed in the next section

Show the ground-state electronic confi gurations of Li + and F −

Solution

Loss of the one valence electron from Li gives Li + which has the same electronic confi guration as

He, while gain of one electron by F gives F − with the same electronic confi guration as Ne

Li + : 1s 2 F − : 1s 2 2s 2 2p 6 (or 1s 2 2s 2 2p x 2 2p y 2 2p z 2 )

Example 1.1

Show the ground-state electronic confi gurations of Na + and Cl − Exercise 1.6

a Ionization energy and electron affi nity

The energy needed to remove an electron from an atom is called its ionization energy

(or ionization potential), I.E This process always requires energy so ionization

ener-gies are always positive The smaller the positive charge experienced by the valence

electrons (the charge of the nucleus shielded to some extent by the core electrons), the

easier it is for one to be removed and, therefore, the smaller the ionization energy An

atom of an element of low ionization energy can readily become a cation and is said to

be electropositive

On the other hand, the energy released when an atom gains an electron is called the

electron affi nity , E.A An element of high electron affi nity is said to be strongly

electro-negative ; an atom of such an element can readily become an anion with the evolution of

appreciable energy

Table 1.3 lists values for the ionization energies (red) and electron affi nities (blue) of

atoms in electron volts (eV) in the form of the periodic table

It follows from the defi nition of electron

affi nity that a positive E.A converts into a negative

enthalpy of reaction if the same process is represented

as a conventional thermochemical equation,

i.e E.A = –Δ EA H (although

enthalpies of reaction are normally given in kJ mol −1 )

~0

B 8.30

0.24

C 11.26

1.27

N 14.53

~0

O 13.62

1.47

F 17.42

3.34

Ne 21.56

~0

Al 5.99

0.46

Si 8.15

1.24

P 10.49

0.77

S 10.36

2.08

Cl 12.97

3.61

Ar 15.76

~0

Values are given in eV (1 eV = 96.485 kJ mol −1 )