Organic Chemistry : A Mechanistic Approach

681 Pages·2013·12.06 MB·English

by  Tadashi Okuyama

Organic
Chemistry
Periodic Table of the Elements
1 18
1 2
H He
hydrogen helium
[1.008] 2 Key: 13 14 15 16 17 4.003
3 4 atomic number 5 6 7 8 9 10
Li Be Symbol B C N O F Ne
lithium beryllium name boron carbon nitrogen oxygen fluorine neon
[6.941] 9.012 standard atomic weight [10.81] [12.01] [14.01] [16.00] 19.00 20.18
11 12 13 14 15 16 17 18
Na Mg Al Si P S Cl Ar
sodium magnesium aluminium silicon phosphorus sulfur chlorine argon
3 4 5 6 7 8 9 10 11 12
22.99 24.31 26.98 [28.09] 30.97 [32.07] [35.45] 39.95
19 20 21 2222 23 2244 25 26 27 28 29 30 31 32 33 34 35 36
K Ca Sc TTii V CCrr Mn Fe Co Ni Cu Zn Ga Ge As Se Br Kr
potassium calcium scandium ttiittaanniiuumm vanadium cchhrroommiiuumm manganese iron cobalt nickel copper zinc gallium germanium arsenic selenium bromine krypton
39.10 40.08 44.96 4477..8877 50.94 5522..0000 54.94 55.85 58.93 58.69 63.55 65.38(2) 69.72 72.63 74.92 78.96(3) 79.90 83.80
37 3388 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54
Rb SSrr Y Zr Nb Mo Tc Ru Rh Pd Ag Cd In Sn Sb Te I Xe
rubidium ssttrroonnttiiuumm yttrium zirconium niobium molybdenum technetium ruthenium rhodium palladium silver cadmium indium tin antimony tellurium iodine xenon
85.47 8877..6622 88.91 91.22 92.91 95.96(2) [99] 101.1 102.9 106.4 107.9 112.4 114.8 118.7 121.8 127.6 126.9 131.3
5555 56 57-71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86
CCss Ba Hf Ta W Re Os Ir Pt Au Hg Tl Pb Bi Po At Rn
lanthanoids
ccaaeessiiuumm barium hafnium tantalum tungsten rhenium osmium iridium platinum gold mercury thallium lead bismuth polonium astatine radon
113322..99 137.3 178.5 180.9 183.8 186.2 190.2 192.2 195.1 197.0 200.6 [204.4] 207.2 209.0 [210] [210] [222]
87 88 89-103 104 105 106 107 108 109 110 111 112 114 116
Fr Ra Rf Db Sg Bh Hs Mt Ds Rg Cn Fl Lv
actinoids
francium radium rutherfordium dubnium seaborgium bohrium hassium meitnerium darmstadtium roentgenium copernicium flerovium livermorium
[223] [226] [267] [268] [271] [272] [277] [276] [281] [280] [285]
57 58 59 60 61 62 63 64 65 66 67 68 69 70 71
La Ce Pr Nd Pm Sm Eu Gd Tb Dy Ho Er Tm Yb Lu
lanthanum cerium praseodymium neodymium promethium samarium europium gadolinium terbium dysprosium holmium erbium thulium ytterbium lutetium
138.9 140.1 140.9 144.2 [145] 150.4 152.0 157.3 158.9 162.5 164.9 167.3 168.9 173.1 175.0
89 90 91 92 93 94 95 96 97 98 99 100 101 102 103
Ac Th Pa U Np Pu Am Cm Bk Cf Es Fm Md No Lr
actinium thorium protactinium uranium neptunium plutonium americium curium berkelium californium einsteinium fermium mendelevium nobelium lawrencium
[227] 232.0 231.0 238.0 [237] [239] [243] [247] [247] [252] [252] [257] [258] [259] [262]
Notes
The uncertainty of an atomic weight value is ±1 in the last digit unless a different value is given in parentheses. No values are given
for elements which have no natural stable isotopes; for such elements, a mass number of a typical radioisotope is given in parentheses.
Organic
Chemistry
a mechanistic approach

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Japanese version published by Maruzen Publishing Co., Ltd., Japan
© Tadashi Okuyama 2008.
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Foreword
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
Preface
Organic chemistry is a mature branch of science which continues to expand in the sense that new reac-
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
in medicine and other areas of science and technology. A consequence of the huge and increasing 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 in-
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 . . . vii
Online Support
Organic Chemistry: a mechanistic approach is accompanied by a website that features study and teach-
ing aids.
For students:
• 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 w ww.oxfordtextbooks.co.uk/orc/okuyama/ .
You can also explore organic reaction mechanisms at w ww.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, O rganic 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.
A Note to Students
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 r eactivity 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 h ow 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.
drivingforce
(electronpull)
+ H pull + H H newbond H
O H O O O +
HO O H OH2
H H
R OR' proton R OR' R OR'
transfer
HO OH
+ H O+
3
proton
R OR'
transfer
tetrahedralintermediate
drivingforce
nucleophile (electronpush)
push O
newbond
HO– O HO O–
R OH RCO –
2
R OR' R OR'
+ –OR' + R'OH
addition elimination proton
leavinggroup transfer
substitution(hydrolysis)
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.