Organic chemistry structure, mechanism and synthesis by robert j ouellette and j david rawn

ChAPter 2 PArt i: funCtionAl grouPs And their ProPerties 2.1 introduCtion to funCtionAl grouPs: hydroCArbons And hAloAlKAnes 41 ChAPter 3 introduCtion to orgAniC reACtion meChAnisms... C

O rganic c hemistry :

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O rganic c hemistry :

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Acknowledgments xxxiii

ChAPter 1 struCture And bonding in orgAniC ComPounds

1.8 vAlenCe shell eleCtron PAir rePulsion theory 15

1.17 effeCt of hybridizAtion on bond length And bond strength 27

ChAPter 2 PArt i: funCtionAl grouPs And their ProPerties

2.1 introduCtion to funCtionAl grouPs: hydroCArbons And hAloAlKAnes 41

ChAPter 3 introduCtion to orgAniC reACtion meChAnisms

brønsted-lowry Acids and bases 75

3.5 stAndArd free energy ChAnges in ChemiCAl reACtions 86

3.9 struCtures And stAbilities of CArbon rAdiCAls, CArboCAtions,

ChAPter 4 AlKAnes And CyCloAlKAnes: struCtures And reACtions

densities of Alkanes 144

4.13 ChlorinAtion of An AlKAne—A rAdiCAl reACtion 148

ChAPter 5 AlKenes struCtures And ProPerties

ChAPter 6 AlKenes: Addition reACtions

6.3 the meChAnistiC bAsis of mArKovniKov’s rule 199

8.6 moleCules with two (or more) stereogeniC Centers 254

ChAPter 9 hAloAlKAnes And AlCohols introduCtion to

nuCleoPhiliC substitution And eliminAtion reACtions

9.13 AlternAte methods for the synthesis of AlKyl hAlides 310

8.10 reACtions thAt ProduCe stereogeniC Centers 270

ChAPter 10 nuCleoPhiliC substitution And eliminAtion

reACtions

10.2 biologiCAl sn2 reACtions of sulfur-ContAining nuCleoPhiles 336

10.3 stereoChemistry of nuCleoPhiliC substitution reACtions 337

10.6 effeCts of struCture on ComPeting substitution And eliminAtion

9.17 regioseleCtivity in dehydrAtion reACtions 316

ChAPter 12 Arenes And AromAtiCity

ChAPter 11 ConJugAted AlKenes And AllyliC systems

11.3 moleCulAr orbitAls of ethene And 1,3-butAdiene 361

11.4 struCturAl effeCts of ConJugAtion in 1,3-butAdiene 366

11.6 hÜCKel moleCulAr orbitAls of Allyl systems 375

11.7 eleCtroPhiliC Addition to ConJugAted dienes 379

11.10 ultrAvioltet-visible sPeCtrosCoPy of AlKenes And ConJugAted

systems

386

ChAPter 14 methods for struCture determinAtion

nuCleAr mAgnetiC resonAnCe And mAss sPeCtrometry

ChAPter 13 eleCtroPhiliC AromAtiC substitution

13.2 meChAnism of eleCtroPhiliC AromAtiC substitution 420

13.3 Common eleCtroPhiliC AromAtiC substitution reACtions 422

13.4 substituent effeCts on the reACtivity of benzene rings 429

13.5 interPretAtion of the effeCt of substituents on reACtion rAtes 432

13.8 synthesis of substituted AromAtiC ComPounds 440

12.4 moleCulAr orbitAls of AromAtiC And AntiAromAtiC ComPounds 405

ChAPter 15 AlCohols: reACtions And synthesis

14.4 deteCting sets of noneQuivAlent hydrogen Atoms 458

14.8 effeCt of struCture on CouPling ConstAnts 471

mechanism of the reaction of Alcohols with thionyl Chloride 498

15.10 AlCohol synthesis using grignArd reAgents 518

ChAPter 16 ethers And ePoxides

ChAPter 17 orgAnometAlliC Chemistry of trAnsition metAl

elements And introduCtion to retrosynthesis

17.1 brief overview of trAnsition metAl ComPlexes 567

17.3 overview of PAllAdium CAtAlyzed Cross-CouPling reACtions 573

16.5 synthesis of ethers: AlKoxymerCurAtion-demerCurAtion of AlKenes 542

16.12 sPeCtrosCoPy of ethers, thiols And sulfides 557

17.5 the heCK reACtion 576

17.7 the wilKinson CAtAlyst: homogeneous CAtAlytiC hydrogenAtion 580

17.8 AsymmetriC hydrogenAtion with ChirAl ruthenium CAtAlysts 582

17.9 the grubbs reACtion: A metAthesis reACtion for AlKene synthesis 584

17.10 introduCtion to retrosynthesis: thinKing bACKwArds 586

ChAPter 18 Aldehydes And Ketones

18.3 PhysiCAl ProPerties of Aldehydes And Ketones 600

18.4 oxidAtion-reduCtion reACtions of CArbonyl ComPounds 603

friedel-Crafts Acylation

18.6 synthesis of CArbonyl ComPounds: A Preview 610

19.1 relAtive stAbilities of Aldehydes And Ketones 629

19.4 meChAnisms of ACid- And bAse-CAtAlyzed CArbonyl Addition reACtions 633

19.8 Addition of nitrogen ComPounds to Aldehydes And Ketones 643

ChAPter 20 CArboxyliC ACids

20.2 nomenClAture of CArboxyliC ACids 661

20.9 reACtions of CArboxyliC ACids And their derivAtives: A Preview 680

20.10 Conversion of CArboxyliC ACids into ACyl hAlides 681

20.11 Conversion of CArboxyliC ACids into esters 682

ChAPter 21 CArboxyliC ACid derivAtives

21.1 nomenClAture of CArboxyliC ACid derivAtives 699

21.4 meChAnism of nuCleoPhiliC ACyl substitution 706

ChAPter 22 CondensAtion reACtions of CArbonyl

ComPounds

22.1 the a-CArbon Atom of Aldehydes And Ketones 747

22.4 a-hAlogenAtion reACtions of Aldehydes And Ketones 754

22.8 intrAmoleCulAr Aldol CondensAtion reACtions 763

22.9 ConJugAtion in a-b-unsAturAted Aldehydes And Ketones 765

22.11 the miChAel reACtion And robinson AnnulAtion 770

21.10 infrAred sPeCtrosCoPy of ACyl derivAtives 725

22.15 Aldol-tyPe CondensAtions of ACid derivAtions 781

22.17 miChAel CondensAtions of ACid derivAtives 787

ChAPter 23 Amines And Amides

23.7 synthesis of Amines by substitution reACtions 813

reduction of nitro Compounds 817

ChAPter 24 Aryl hAlides, Phenols, And Anilines

ChAPter 25 PeriCyCliC reACtions

25.3 moleCulAr orbitAls in PeriCyCliC reACtions 877

24.8 substitution reACtions of AryldiAzonium sAlts 861

ChAPter 26 CArbohydrAtes

less Common monosaccharides 912

26.5 CyCliC monosACChArides: hemiACetAls And hemiKetAls 916

ChAPter 27 Amino ACids, PePtides, And Proteins

27.3 isoioniC Point And titrAtion of a-Amino ACids 957

27.10 determinAtion of the Amino ACid ComPosition of Proteins 970determination of the Amino Acid Composition of Proteins by Chemical methods 97027.11 determinAtion of the Amino ACid seQuenCe of Proteins 972

Primary structures and evolutionary relationships 975

ChAPter 28 synthetiC Polymers

hydrogen bonding and Polymer Properties 995

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Writing an organic chemistry book is a large undertaking, and many people are required to bring it

into the world We would like to thank the people who reviewed this manuscript However, since

their identities were not disclosed to us, there is no way for us to cite them individually We know

that reviews of this type take time and effort, and we are grateful for their advice

We would like to thank Dr Thomas Lectka, Professor of Chemistry at Johns Hopkins

University, who provided expert advice on a host of topics His critical comments were invaluable

We would also like to thank Ms Gillian McCallion, who laid out the basic design of this text She

also designed the cover and provided templates for many images within the text There are many

molecular models in this text They were made in Spartan Student, and we would like to thank

Sean Ohlinger—Vice President, General Manager, Wavefunction, Inc.—and his staff for their

technical support

We would like to thank the capable people at Elsevier: Ms Beth Campbell, the

Chemistry Acquisitions Editor, gave us continuous support and encouragement; Ms Jill Cetel,

Editorial Project Manager, oversaw all aspects of a complex production process We would also

like to thank Ms Sharmila Vadivelan, who managed the graphics group that carried out the

composition of the text

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The subject matter of organic chemistry revolves around a single element, carbon It occupies

an inauspicious place in the periodic table, half way across the second period Why is carbon so

important? The answer is that carbon is the most chemically versatile atom Carbon forms chemical

bonds to most of the elements in the periodic table; even more importantly, it forms bonds to

itself As a result, immensely complex structures that can contain tens of thousands of atoms have

been synthesized in the laboratory and made by living cells The purpose of this book is to provide

a structure for learning organic chemistry How are we going to approach as vast and at first glance

impenetrable subject? The subtitle of this text tells us: we will link molecular structure to the

step-by-step processes, called mechanisms, by which reactions occur Then, we will use these reactions to

make new compounds; that is, we will explore organic synthesis

To learn is in some deep sense to see, and this clarity emerges in part because organic

compounds can be divided into classes based on their “functional groups.” A functional group

is a constellation of atoms— for example, a carbon bonded to a halogen, such as a -CH₂Cl

group, that is the site of characteristic chemical reactions Then, we will find that the reactions of

functional groups can be divided into classes of common reaction mechanisms The close interplay

between the “class of compound” and “class of mechanism” provides an overall unity to organic

chemistry The unifying principles that underlie reaction mechanisms provide “keys” that open

many doors By analogy, we can say that functional groups are the anatomy of organic chemistry,

and that reaction mechanisms and their associated energy changes constitute its “physiology.”

To the unity of structure in the form of functional groups, and function in the form of

reaction mechanisms, we have added many biochemical applications These are integrated into the

structure of the text from beginning to end, in every chapter, in every problem set They are not

mere artifacts, as if we were putting a hat on a horse; they illustrate basic structural and mechanistic

principles, and provide a background against which organic chemistry can be seen as one of the

foundation stones of modern biological chemistry

We can say, without too much exaggeration, that you won’t have to memorize in this

course On the other hand, you will have a lot to remember! These slightly contradictory assertions

summarize an essential part of learning any subject, especially one as complex as organic chemistry

It might seem tempting to seek refuge from intellectual difficulty by memorizing a seemingly

infinite number of facts However, even if it were possible to memorize the known facts of organic

chemistry (it isn’t), that feat would avail nothing unless the facts were understood in terms of

underlying general principles Understanding mechanisms of organic reactions is the key to

understanding organic chemistry

How are you going to learn organic chemistry? The answer is surprisingly simple: work

the problems! There are problems at the end of most sections, including a sample problem with

a worked answer Do that one first and then do the adjacent problems In that way, you will have

reviewed each section of each chapter as you proceed There are many more problems at the end

of each chapter They are organized by section and graded in difficulty Do some of these problems

for each section until you are satisfied that you understand the material Finally, don’t study organic

chemistry as a Burmese python eats its monthly lunch, by trying to digest an immense amount at

one sitting (followed by some weeks of indigestion) Instead, study systematically every day That

way you will not fall behind There is too much material, it goes too fast, and it is too complicated

to learn on the night before an exam If you study systematically, you can be confident that you will

succeed in organic chemistry

Success in any endeavor is contagious: once one has learned how to master one thing, that

template provides the foundation for continued success in new ventures

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S tructure and B onding

Organic chemistry began to emerge as a science about 200 years ago By the late eighteenth century, substances had been divided into inorganic and organic compounds In those days, early in the history of organic chemistry, inorganic compounds were isolated from mineral sources, and organic compounds were obtained only from plants or animals Organic compounds were more difficult to study in the laboratory and decomposed more easily than inorganic compounds The differences between inorganic and organic compounds were attributed to a “vital force” that was required for the synthesis of organic compounds It was believed that organic compounds could not be synthesized

in the laboratory without the vital force However, by the middle of the nineteenth century, chemists had learned how to work with organic compounds in the laboratory and how to synthesize them

The organic compounds we will discuss throughout this text contain carbon and a few other elements, such as hydrogen, oxygen, and nitrogen We will also examine compounds containing sul-fur, phosphorus, and halogens Many, more exotic, organic compounds are also known, and organic compounds have been made that contain virtually every element in the periodic table

The molecule shown below is terfenedine, an antihistamine whose formula is C32H41NO2 The structure of terfenedine is an example of the amazing variety of structures of organic compounds They are everywhere in nature, including interstellar space No known living organism can exist with-out organic compounds, and synthetic organic compounds are an integral part of the objects we use every day Their importance cannot easily be exaggerated

The physical and chemical properties of a molecule depend on the bonds that hold it together And these bonds depend on the electron configurations of its atoms Therefore, we will review some of the electronic features of atoms and the periodic properties of the elements before describing bonding and its relation to structure in organic compounds

The elements in the periodic table are arranged by atomic number The elements are

ar-rayed in horizontal rows called periods and vertical columns called groups In this text, we will

1.2 atomic properties

figure 1.2 atomic radii in picometers,

pm (10-12 m)

atomic orbitals

The electrons in an atom occupy atomic orbitals, which are designated by the letters s, p, d, and f

Each orbital can contain a maximum of two electrons An atomic orbital is a mathematical equation

that describes the energy of an electron The square of the equation for the atomic orbital defines the

probability of finding an electron within a given region of space

Orbitals are grouped in shells of increasing energy, designated by the integers 1, 2, 3, 4, , n

These integers are called principal quantum numbers Each shell contains a unique number and

type of orbitals The first shell contains a single 1s orbital The second shell contains one 2s orbital

and three 2p orbitals Each orbital can contain no more than two electrons, and two electrons in any

orbital must have opposite spin We need to consider only the orbitals of the first three shells for the elements commonly found in organic compounds

All s orbitals are spherically symmetrical (Figure 1.1a) The 2s orbital is larger than the 1s orbital A 2s orbital is farther from the nucleus, and it has a higher energy than a 1s orbital The three

p orbitals in a shell are not spherically symmetrical Electron density in each p orbital is concentrated

in two regions or lobes—one on each side of the nucleus The two lobes together are the orbital The shapes of the p orbitals are shown in Figure 1.1b The p orbitals are often designated as px, py, and

pz They are mutually perpendicular to one another, and they are aligned along the x, y, and z axes

Although the orientations of the px, py, and pz orbitals differ, the electrons in each p orbital have equal energies

Orbitals of the same type within a shell constitute a group called a subshell For example,

an s subshell has one orbital and can contain only two electrons In contrast, a p subshell, which begins in period two, contains three p orbitals and can contain a total of six electrons

Electrons are distributed in subshells to give an electron configuration that has the lowest energy The order of increasing energy of subshells is 1s < 2s < 2p < 3s < 3p for elements of atomic number less than 18 For any subshell, the lowest energy state is the arrangement that maximizes

the number of electrons having the same spin This generalization is Hund’s Rule This means that

electrons first occupy orbitals one at a time within subshells before pairing in a common orbital

Table 1.1 shows the atomic numbers and electron configurations for the first two periods in the periodic table

table 1.1 electron configurations of first and second period elements

Element Atomic Number 1s 2s 2p x 2p y 2p z Electron Configuration

(a) An orbital is a boundary surface

enclosing a volume where electrons can

be located with 90% probability An s

orbital has a spherical boundary surface

(b) Boundary surfaces of the three

mutually perpendicular 2p orbitals

Each orbital can hold a maximum of

two electrons The + and – signs on the

orbitals refer to the phase of the orbital,

not to the charge of the orbital.

valence shell electronsElectrons in filled, lower energy shells of atoms have no role in determining the structure of molecules, and they do not participate in chemical reactions because they are held too tightly to the nucleus Only the higher energy electrons, which are located in the outermost shell, called the

valence shell , participate in chemical bonding These are the valence electrons For example,

the single electron of the hydrogen atom is a valence electron The number of valence electrons for the common atoms contained in organic molecules is given by their group number in the periodic table Thus, carbon, nitrogen, and oxygen atoms have four, five, and six valence electrons, respectively With this information we can understand how these elements combine to form organic compounds

1.2

atomic properties

The elements in the periodic table are arranged by atomic number The elements are arranged

in horizontal rows called periods and vertical columns called groups The physical and

chemical properties of an element can be estimated from its position in the periodic table Two

properties that help us explain the properties of organic compounds are the atomic radius and electronegativity

atomic radiusThe overall shape of an atom is spherical, and its volume depends both on the number of electrons and on the energies of the orbitals the electrons occupy The sizes of some atoms, expressed as the atomic radius, in picometers (pm,10-12 m), are given in Figure 1.2 in a greatly abbreviated peri-odic table that shows the atoms we will most commonly encounter in our discussion of organic compounds Atomic radii increase from top to bottom in a group of the periodic table because the electrons in each new shell are located at greater distances from the nucleus Thus, the atomic radius

of sulfur is greater than that of oxygen, and the radii of the halogens increase in the order F < Cl <

Br < I

The atomic radius decreases from left to right across a period Although electrons are cated in the same energy level within the s and p orbitals of the elements, the nuclear charge increases from left to right within a period These electrons are not shielded very well from the nuclear charge, and the atomic radius decreases The radii of the common elements in organic compounds decrease

to give an inert gas configuration Thus, we find that electronegativity increases from left to right across the periodic table Electronegativity values increase in period 2 in the order C < N < O < F