A GUIDEBOOK TO MECHANISM IN ORGANIC CHEMISTRY

Bonding in Carbon Compounds BONDING IN CARBON COMPOUNDS Bond formation between two atoms is then envisaged as the progres­ sive overlapping of the atomic orbitals of the two participati

In this new edition several additional topics, for example the

nitrosation of amines, diazo-coupling, ester formation and

hydrolysis, anti decarboxylation, are included and many

sections of the previous edition have been rewritten in whole

or in part to clarify the argument v, Some press opinions of the first edition: <•

' a pleasure to read and at use for it is

\£t£$&1l& language, the prifttiug is good, with a

•j tietiV type of emphasis where necessary,'and

t > Excellent In short, Dr Sykes has written

^ which can be strongly recommended to

:ent alike.' Cambridge Review

'First year ci*>- iistry undergraduates should be dancing in the

sue?-' for joy v the news of this publication ."The book

is >•„•.».• ;.fvlly produced and should bring home to many people

that orjiiiic Chemistry is not an over-complicated form of

cooker ' Peter Sykes has done a really valuable job.'

'Dr Sykes has achieved the remarkable feat of perfu

presentation of a subject not usually in a form easily as

to the student The reproduction of fonftulae is sple

the general presentation admirable to a icgrec No

is felt, therefore, in unreservedly r e c o m p i l i n g this

final B.Sc or Dip.Tech students.' ^-"•hnical Journal

LONGNMS

\A Guidebook to Mechanism

I in Organic Chemistry

L O N G M A N S

48 Grosvenor Street, L o n d o n , W i

Associated companies, branches and representatives

throughout the world

1 Structure, Reactivity arid Mechanism 1

2 T h e Strengths rtfcXtids and Bases 3 8

^^ldcQpfaYic S u b s t i t u t i o n , - ^ d ^ a t u r a t e d Carbon A t o m 58

4 , C a r b o n i u m Ions, Electro^-JDeficient Nitrogen and Oxygen

A t o m s and their Reactions ? 80

5 Electrophilic and Nucleophilic Substitution in Aromatic #

Systems • ^H 1 0 1

6 ^-Addition, t o C a r b o n - C a r b o n Double Bonds 137

C^ASdition' t o Carbon-Oxygen Double Bonds 158

8'''Elimination Reactions 189

9 Carbanions and their R e a c t i o n s : 210

10 ^RacJ-icals and their Reactions 231

Select g?6liography 261

D

Index 263

T H E g r e a t - d ^ e l o p m e n t of*the theory of organic chemistry o r more

particularly-of o u r understanding of the mechanism of the reactions

o^earbori compounds, which h?" ccurred during the past thirty

^years or soVhas wrought a vast change in outlook over the whole of

the science A t one time organic <$iemistry appeared t o the student as

a vast body of facts,, often apparently unconnected, which simply had

to be learnt, but the iaVte recent developments in theory have changed

alltjjfe so that organic chemistrjys^now a much more ordered body

ofknowledgei in which a logical pattern can be clearly seen Naturally

enough during the long period^of development from the initial ideas

of Lapworth a n d Robinson organic chemical theory has undergone continuous modification a n d it is only in comparatively recent times that it h a s become of such evident generality (although doubtless still far from finality) that its value a n d importance t o the under­

graduate student has b e c \ m e fully realised A s a result the teaching

o f ^ a n i c chemistry has been, t o some extent, in a state of flux a n d a variety o f experiments have been m a d e a n d a substantial number of

B r o k s p r o d u c e d setting out different approaches to it While it is the

writer's opinion that it is unsatisfactory to teach first the main

factual part of the subject a n d subsequently t o introduce the theory

of reaction mechanism, he is equally convinced that at the present time it is quite impracticable t o concentrate almost entirely on theory

and virtually to ignore the factual "part of the subject Organic

chemjpal theory h a s n o t yet reached a level a t which it permits

prediction with any certainty of the precise behaviour of m a n y members of the m o r e complex carbon compounds which are of everyday occurrence in the practice of the science Sound theory is vital t o the well-being of organic chemistry; b u t organic chemistry remains essentially a n experimental science

In Cambridge we are seeking the middle way, endeavouring t o

build u p both aspects of the subject in concert so that there is a

Foreword

minimum of separation between fact and theory T o achieve this the student is introduced at an early stage t o the theoretical principles involved and t o the essential reaction mechanisms illusfated by a modest number of representative examples With this approach is coupled a more factual treatment covering the chemistry of the major groups of carbon compounds D r Sykes [who has been intimately associated with this approach} has now written this aptly-named ' G u i d e b o o k ' to reaction mechanism which sets out in

an admirably lucid way what the student requiresras a complement

t o his factual reading I warmly commefld it as a bopjp,which will enable students to rationalise m a n y of fllrfacts o f organic chemistry,

t o appreciate the logic of the subject and in so doing t o minimiseshe memory work involved in mastering it *

^ A R T O D D

26th April, 1961 ; „•

>» •'

f

\

P R E F A C E T O S E C O N D E D I T I O N

I N p r e p a r i n g this second edition I have been most anxious that it

should not-increase, markedly in size (or price!) for I feel sure that

wjjat utility the b o o k has-been found t o possess stems in n o small

p a r t from its being short in"length ( a n d cheap in price!) I have, there­

fore, added only those topics wjjich are generally felt t o be vital

omissions, e.g nitrpsation of amines, diazo-coupling, ester formation

a n d hydrolysis, decarboxylation, etc., b u t I have also sought t o

eliminate errors a n d t o clarify t h j ^ r g u m e n t throughout, which has

i n v o l v e d rewriting m a n y of the sections in whole o r in part

M a n y readers have been kind enough t o write t o me a n d I have

where possible adopted their s u g g e s t i o n s ; in this connection I owe a

particular debt to Professor D r W Liittke of Gottingen and D r P

Hocks o f Berlin, the translators of the G e r m a n edition M r G M

Clarke a n d D r D H M a r r i a n of this University have kindly read t h e

proofs of this second edi^pn a n d they t o o have made valuable

sugges-t i q ^ f o r which I a m mossugges-t grasugges-teful

Cambridge, , PETER SYKES

Affil 1964

, P R E F A C E

T H E last twenty-five years have seen a n enormous increase in our

knowledge of {he reactions of organic c o m p o u n d s and, in particular,

o f t h e actual detailed p a t h w a y o r mechanism b y which these reactions

take place This understanding has largely come a b o u t from the

application of electronic theories—so successful in other fields—to

organic chemistry, a n d has resulted n o t only in a n extremely valuable

systematisation a n d explanation of the vast, disparate mass of

existing facts, b u t has also m a d e it possible t o specify, in advance, the

conditions necessary for the successful carrying o u t of m a n y new a n d

useful procedures

Preface *

T h e new approach avoids the learning of vast masses of apparently

unconnected facts—which h a s been the characteristic of organic

chemistry in the past—and helps a n d encourages the J h e m i s t t o

think for himself: far from requiring a chemist t o k n e w more, it

enables h i m to m a k e infinitely better use of what he already does

know It marks the greater effectiveness of really understanding the

underlying principles rather than merely knowing by rote A t the

same time it is well t o emphasise that the complexity of organic

compounds in general is such that the rigorous application of

quantum-mechanical principles to them k impossible Assumptions

and approximations have t o be made*before useful generalisations

can be worked o u t a n d it is at this point t h a t there is particular ne^d

for strictly chemical skill a n d insight: the-day of organic chemistry •

from the armchair is far from being with us yet!

This new a n d effective way of thinking a b o u t organic chemistry

has been the subject of several large monographs b u t a smaller,

compact b o o k is still required thaUntroduces the essentials, t h ^ e r y

vocabulary of t h e subject, t o t h e scholarship candidate, to^Hfe

beginning undergraduate a n d technical college student, a n d t o the

chemist whose professional education 1ias been along strictly classical

lines T h a t is t h e a i m of this book, which h a s grown o u t of t h e

author's lecture courses at Cambridge a n d his many years spent in

supervising undergraduates

T h e minimum of space h a s p u r p o s e l ^ b e e n spent o n valency

theory as such for not only is that adequately treated elsewhere^fcut

the student's real need is t o gain as much experience as possible in

seeing how theoretical ideas work o u t in practice: in explainingfthe

course taken by actual reactions Thus the first chapter is intended t o

give a succinct statement of the basic principles employed a n d the

rest of the b o o k shows how they work o u t in explaining the variation

of reactivity with structure, the occurrence of three main classes of

reagent—electrophiles, nucleophiles a n d radicals—and their be­

haviour in t h e fundamental reactions of organic chemisjxy—

substitution, addition, elimination a n d rearrangement In all cases,

the examples chosen as illustrations have been kept as simple as

possible so t h a t the essential features of the process a r e n o t confused

by extraneous and inessential detail

Detailed references to the original literature are not included as

the author's experience leads h i m t o believe that in a b o o k of such a

size a n d scope the limited space available can be better employed A

select bibliography is, however, included in which the student's

attention is drawn t o larger sources of information t o which h e can

now progiess a n d reference is made t o t h e particular virtues of a

number o f t h e sources quoted

I a m most grateful t o my mentor of many years, Professor Sir

Alexander T o d d , for his Foreword a n d t o my colleagues D r J Biggs

(now of the University of Hull), D r V M Clark, D r A R Katritzky,

Dr D H Marrian and t o my wife, w h o have read the manuscript in

whole o r in part a n d m a d e very many useful suggestions I should

also like t o express my gratitude t o the Rockefeller F o u n d a t i o n for

a grant whicn enabled m e , J p 1959, t o visit the United States a n d

stay a t Harvard University! Northwestern University, the University

• of Illinois, Oberlin College and the Georgia Institute of Technology

t o study t h e teaching of mechanistic organic chemistry t o under­

graduates a n d graduate students M a n y interesting discussions,

particularly with Pressors F G Bordwell, Nelson J Leonard a n d

J a c k H i n e , influenced a number of the ideas developed in this book

M ^ m d e b t e d h e s s t o the original literature and t o other publications,

in particular Ingold's Structure and Mechanism in Organic Chemistry,

Gould's Mechanism and Struclttrf in Organic Chemistry, Alexander's

Ionic Organic Reactions and Hine's Physical Organic Chemistry will

be apparent t o many who read here Finally I should like t o express

my deep appreciation t o Longmans, a n d t o t h e printers for ttie'ir

unfailing patience a n d f^j t h e extreme trouble t o which they have

gojpMo produce that rare phenomenon, structural formulae that

are both clear and aesthetically satisfying

Cambridge, PETER SYKES

April 1961

t.-o xiii

1 S T R U C T U R E , R E A C T I V I T Y A N D M E C H A N I S M \

T H E chief advantage of a mechanistic approach t o the vast array of disparate information t h a t makes up organic chemistry is the way in which a relttively small m u a b e r of guiding principles can be used, not only t o explain and interrelate existing facts b u t t o forecast the outcome of changing the conditions under which already k n o w n reactions are carried out and t o foretell t h e products that m a y be expected from new ones It is the business of this chapter t o outline some of these guidingprinciples and t o show how they work As it is

t h e c o m p o u n d s of carbon with which we shall be dealing, something lflnst first be said about the way in which carbon atoms can form bonds with other atoms, especially with other carbon atoms

ATOMIC ORBITALS

The carbon a t o m has, outside its nucleus, six electrons which, offthe Bohr theory of a t o m i d ^ t r u c t u r e , were believed t o be arranged in ojjrits a t increasing distance from the nucleus These orbits repre­sented gradually increasing levels of energy, t h a t of lowest energy, the

Is, accommodating two electrons, the next,, the 2s, also accommodat­

ing t w o electrons, and the remaining two electrons of a carbon atom

going into t h e 2p level, which is actually capable of accommodating a

total of six electrons

T h e Heisenberg indeterminacy principle and the wave-mechanical view o f the electron have m a d e us d o away with anything so precisely defined as actual orbits, and instead we can now only quote the rela­tive probabilities of finding an electron at various distances from the nucleus; T h e classical orbits have, therefore, been replaced by three-

dimensional orbitals, which can be said t o represent the shape and size

of the space a r o u n d the nucleus in which there is the greatest p r o ­bability of finding a particular electron: they are, indeed, a sort of three-dimensional electronic contour O n e limitation t h a t theory im­poses on such orbitals is t h a t each may accommodate not more t h a n

two electrons, these electrons being distinguished from each other by

having opposed (' p a i r e d ' ) spins

It can be shown from wave-mechanical calculations ttaat the Is

orbital (corresponding t o the classical K shell) is spherically symme­

trical a b o u t t h e nucleus a n d t h a t t h e 2s orbital is similarly spherically

symmetrical but at a greater distance from the nucleus; there is a

region between the two latter orbitals where the probability of finding

an electron approaches zero (a spherical nodal surface):

spherical nodal surface

3p q f v ^

/ M shell g g l ;

2s If }L shell

U K shell 1*

As yet, this m a r k s n o radical departure from t h e classical picture

of orbits, but with the 2p level (the continuation* of the L shell) a dif­

ference becomes apparent Theory mow requires the existence of tfttg^

2/7 orbitals, all of the same energy a n d shape, arranged mutually at

right-angles along notional x, y and z ajies and, therefore, designated

as 2p x , 2p y a n d 2p„ respectively Further, these three 2p orbitals are

found t o be n o t spherically symmetrical, like the Is and 2s, but

* dumb-bell' shaped with a plane, in which there is zero probability

of finding an electron (nodal plane), passing through the nucleus

(at right-angles t o t h e x, y a n d z axes, respectively) and so separating

the two halves of each dumb-bell: ^

plane '

2p x 2p y 2 Pi 2p x , 2p y and Ip,

combined

W e can thus designate t h e distribution of t h e six electrons of the

carbon atom, in orbitals, as I s2! ?2 2p\2p y ; orbitals of equal energy

(e.g., 2p„ 2p y , 2p,) accommodating a single electron, in turn, before

any takes u p a second one—the 2p z orbital thus remains unoccupied

Bonding in Carbon Compounds

BONDING IN CARBON COMPOUNDS

Bond formation between two atoms is then envisaged as the progres­

sive overlapping of the atomic orbitals of the two participating

The 2s orbital takes u p its full complement of two electrons before the 2p orbitals begin t o be occupied, however, as it is a t a slightly lower e n e ^ y level This, however, represents the ground state of the carbon a t o m in which only two unpaired electrons (in the 2p x and

2p y orbitals) are available for the formation of bonds with other

a t o m s , i.e a t first sight carbon might appear t o be only divalent

It is however energetically worthwhile for the carbon a t o m to assume

an excited state by uncoupling the 2s 2 electrons and promoting one of

them t o the vacant 2p z orbital for, by doing so, it now has four unpaired electrons and is thus able t o form four, rather t h a n only two, bonds

with other atoms or groups ;14he large a m o u n t of energy produced by forming these two extra bonds considerably outweighs t h a t required

• ( « 9 7 kcal/mole) for the initial 2 «2 uncoupling and 2 5 - > 2 J P promotion

C a r b o n in order t o exhibit its normal and characteristic quadrivalency

thus assumes the electron distribution, Is 2 2s l 2p\ 2p\ 2p\

0

^ H Y B R I D A T I O N

C a r b o n does not, however, exert its quadrivalency by the direct use of

these four orbitals t o form t h r i e bonds of one type with the three 2p orbitals and one of a different nature with the 2s orbital Calculation

shows t h a t by blending these four orbitals so as t o form four new, identical and symmetrically disposed orbitals inclined t o each other

a t 1 0 9 ° 2 8 ' (the normal tetrahedral angle), it is possible t o form four stronger, more stable b o n i s The observed behaviour of a carbon a t o m

dm thus again be justified o n energetic grounds These four new

orbitals are designated as sp 3 hybrids and the process by which they are

obtained as hybridisation:

a t o m s , the greater the possible overlapping, the stronger the bond so

formed When t h e a t o m s have come sufficiently close together, it can

be shown t h a t their two atomic orbitals are replaced byfv/o mole­

cular orbitals, one having less energy and the other more than the

sum of the energies of the two separate atomic orbitals These two

new molecular orbitals spread over b o t h a t o m s and either m a y con­

tain the two electrons The molecular orbital of reduced energy is

called the bonding orbital and constitutes a stable b o n d between the

two a t o m s ; the molecular orbital of increased energy is called the

anti-bonding orbital and need n o t here be further consjdered in the

formation of stable bonds between atdfcs

In the stable bond so formed the two bonding electrons tend t o be

concentrated along the line joining the nuclei of the two participating

atoms, i.e the molecular orbital is^said t o be localised Such localised

electrons are often referred to as a electrons and the covalent bond

so formed as a a b o n d T h u s on combining with hydrogen, the four

hybrid sp 3 atomic orbitals of cajbon overlap with t h e I s atomic

orbitals of four hydrogen atoms t o form four identical, s t r o n | ,

hybrid sp 3 or a b o n d s , making angles of 109° 2 8 ' with each other (the

regular tetrahedral angle), in meth^jfe'.^A similar, exactly regular,

tetrahedral structure will result with, for example, C C 14 but with, say,

C H2C 12, though the arrangement will remain tetrahedral, it will

depart very slightly from exact symmetry; the two large chlorine

atoms will take up more r o o m than hydrodSn so t h a t the H — C — H

and CI—C—CI b o n d angles will differ slightly from 109° 2 8 ' a«d

from each other

(i) Carbon-carbon single bonds

The combination of two carbon a t o m s , for example in ethane, results

from the overlap of two sp 3 atomic orbitals, one from^each carbon

a t o m , t o form a strong a b o n d between them T h e c a r b o n - c a r b o n

b o n d length in saturated compounds is found t o be pretty constant—

1 • 54 A W e have not, however, defined a unique structure for e t h a n e ;

the a b o n d joining the two carbon atoms is symmetrical a b o u t a line

joining the two nuclei, and, theoretically, an infinite variety of differ­

ent structures is still possible, denned by the position o f the hydrogens

on one carbon a t o m relative t o the position of those on the other The

two extremes of the possible species are known asjthe eclipsed and

staggered forms; they a n d t h e infinite variety of structures lying

between them are k n o w n as conformations of the ethane molecule

Bonding in Carbon Compounds

Conformations are denned as different arrangements of the same

g r o u p of atoms that can be converted into one another without the breaking any bonds

H

% Eclipsed Staggered

T h e staggered conformation is likely t o be the more stable of the two for the hydrogen atoms are as far apart as they can get and any interaction is thus at a minimum, whereas in the eclipsed con­formation they are suffering the m a x i m u m of crowding T h e long cherished principle of free rotation a b o u t a c a r b o n - c a r b o n single ttBfici is n o t contravened, howeve'r, as it has been shown t h a t the eclipsed and staggered conformations differ by only « 3 kcal/mole in energy content a n d this is'srffell enough t o allow their ready inter-conversion t h r o u g h the agency of ordinary thermal motions at r o o m

temperature T h a t such crowding can lead t o a real restriction of

rotation a b o u t a c a r b o n - c a r b o n single b o n d h a s been confirmeTP by the isolation of two forrik of C H B r a - C H B r j , t h o u g h admittedly only

a ^ l o w temperatures wnere collisions between molecules d o not provide enough energy t o effect the interconversion

(ii) Carbon-carbon double bonds

I n ethylene each carbon atom is bonded to only three other a t o m s , two

hydrogens and one carbon Strong a bonds are formed with these

three a t o m s by the use of three hybrid orbitals derived by hybridising

t h e Is and, this time, two only of the carbon atom's 2p atomic orbitals—

an a t o m will normally only mobilise as many hybrid orbitals as it has

a t o m s o r groups t o form strong a bonds with T h e resultant sp 2 hybrid orbitals all lie in the same plane and are inclined at 120° t o each other

(plane trigonal orbitals) In forming the molecule of ethylene, two of the

sp 2 orbitals of each carbon a t o m are seen as overlapping with the Is orbitals of two hydrogen atoms t o form two strong a C — H bonds,

while the third s p2 orbital of each carbon atom is used t o form a strong

a C—C b o n d between them

This then leaves, o n each carbon a t o m , one unhybridised 2p

atomic orbital a t right angles t o the plane containing the carbon and

hydrogen atoms These two 2p atomic orbitals are p a r a l £ l t o each

other a n d c a n themselves overlap t o form a molecular orbital, spread­ing over b o t h carbon atoms and situated above a n d below the plane containing t h e two carbon and four hydrogen a t o m s (dotted lines

indicate b o n d s t o atoms lying behind the plane of the paper a n d •*

t o those lying in front of it):

h 4 ~ 1 v h

T h e electrons occupying this new m o l e c u l a r o r b i t a l ' a r e known as

n electrons and the orbital itself a s o r b i t a l The new ir b o n d thfltis

t h u s formed has the effect of drawing the carbon a t o m s closer

t5-gether thus the C = C distance in ethylene is 1 • 33 A compared with a

C — C distance of 1*54 A in ethanglfThe lateral overlap of t h e p

orbitals that occurs in forming a 7r.bond is less effective t h a n the linear

overlap t h a t occurs in forming a a b o n d and the former is thus weaker

thaiTthe latter This is reflected in the fact t h a t the energy of a c a r b o n carbon double b o n d , though m o r e t h a n ^fat of a single b o n d is, indeed, less t h a n twice as m u c h T h u s the C—C b o n d energy in ethaqp

is 83 kcal/mole, while that of C = C in ethylene is only 143 kcal/mole

-T h e overlap of the t w o 2p atomic orbitals, and hence the strength of

t h e n b o n d , will clearly b e a t a m a x i m u m when t h e two carbon a n d

four hydrogen a t o m s are exactly coplanar, for it is only in this

position t h a t the p atomic orbitals are exactly parallel t o each other

a n d thus capable of the maximum overlapping A n y disturbance of

this coplanar state by twisting about the a b o n d joining the two

c a r b o n a t o m s would lead t o reduction in w overlapping a n d hence a

decrease in t h e strength of the ir b o n d : it will thus be resisted A

theoretical justification is t h u s provided for t h e long observed resistance t o rotation a b o u t a c a r b o n - c a r b o n double b o n d T h e

distribution of the IT electrons in two layers^ above a n d below the

plane of the molecule, and extending beyond the c a r b o n - c a r b o n bond axis means that a region of negative charge is effectively waiting there to welcome any electron-seeking reagents (e.g oxidising agents),

* Bonding in Carbon Compounds

T h e acetylene molecule is thus effectively sheathed in a cylinder of negative charge T h e C = C bond energy is 194 kcal/mole, so t h a t the increment due t o the third b o n d is less than t h a t occurring o n going from a single t o a double b o n d The C = C b o n d distance is 1 -20 A

so t h a t the carbon atoms have been drawn still further together, but here again the decrement on going C = C - > - C = C is smaller than t h a t

on going C — C - » - C = C

(iv) Conjugated dienes, etc

A n explanation in similar terms can be adduced for the differences in behaviour between dienes (and also in compounds containing more

than two double bonds) in which the double bonds are conjugated (I)

and those in which they are isolated (II):

so t h a t it comes as n o surprise t o realise t h a t the characteristic reac­tions of a c a r b o n - c a r b o n double b o n d are predominantly with such reagents ( y p 137) Here the classical picture of a double b o n d has been superseded by a view in which the two bonds joining the carbon atoms, far from being identical, are believed t o be different in nature, strength and position

(iii) Carbon-carbon triple bonds

I n acetylene each carbon a t o m is bonded to only two other atoms, one hydrogen a ^ one carbon Strong a bonds are formed with these two

a t o m s by t h e use of two hybrid orbitals derived by hybridising the 2s and, this time, one only of the carbon atom's 2p orbitals T h e resultant

sp 1 hybrid orbitals are co-linear T h u s , in forming the molecule of

acetylene, these hybrid orbitals ore used t o form strong a b o n d s

between each carbon a t o m a n d one hydrogen a t o m and between the two carbon atoms themselves, resulting in a linear molecule having

fttff«unhvbridised 2p atomic orbitals, a t right angles t o each other, on

each of the two carbon atoms T h e atomic orbitals on one carbon a t o m are parallel t o those on the othgr and can thus overlap with each other

resulting in the formation of tw» it bonds in planes at right angles t o

each other:

in which the electrons are said t o be delocalised as they are n o w spread

over, and are held in c o m m o n by, the whole of the conjugated

system There will, of course, need t o be two such delocalised orbitals

as n o orbital can contain m o r e t h a n two electrons and four electrons are here involved The result is a region of negative charge above and below the plane containing all the atoms in the molecule

The better description that this view affords of the properties of conjugated dienes including the possibility of adding, for example, bromine t o the ends of the system (1:4-addition) rather than merely

t o one of a pair of double bonds (l':2-addition) is discussed below ( p 150)

Bonding in Carbon Compounds

It should, perhaps, be mentioned t h a t such delocalisation can only

occur when all the atoms in t h e diene are essentially in the same plane

F o r in other positions, (e.g XIV, p 13), possible owing t o rotation

a b o u t the central C—C b o n d , the n atomic orbitals o n c a r b o n a t o m s

2 a n d 3 would' n o t be parallel and could thus n o t overlap a t all

effectively The effect of the delocalisation that actually takes place is

thus t o impose considerable restriction on rotation about the central

C—C b o n d , observed as a preferred orientation of the c o m p o u n d

(v) Benzene and aromaticiry

A somewhat similar state oNTffairs occurs with benzene T h e k n o w n

planar structure of the molecule implies sp 2 hybridisation, with p

• atomic orbitals, a t right angles t o t h e plane of the nucleus, on each of

the six carbon atoms (VI): •

(VIII) (VI) ( V ©

Overlapping could, of co%rse, take place 1:2, 3:4, 5:6, or 1:6, 5:4,

3 d ? leading t o formulations corresponding t o t h e Kekule structures

& * (e.g VII) but,, in fact, delocalisation takes place as with butadiene,

though to a very much greater extent, leading to a cyclic tr orbital

embracing all six carbon atoms of the ring Other orbitals in addition

t o the above are required to accommodate the total of six electrons

(cf p 1), b u t the net result is annular rings of negative charge above

and below the plane of the nucleus (VIII)

Support for this view is provided by the fact t h a t all the c a r b o n

-carbon b o n d lengths in benzene are the same, i.e all the bonds are of

exactly the same character, all being somewhere in between double

a n d single b o n d s as is revealed by their length, 1 • 39 A T h e degree of

'multiplicity' of a b o n d is usually expressed as the bond order, which

is one for a single, two for a double and three for a triple b o n d The

relation between b o n d order a n d b o n d length is exemplified by a

curve of the type

conferred by the cyclic delocalisation of the IT electrons over the six

carbon atoms coupled with the fact tfeat the angle between the plane

trigonal a bonds is at its optimum vafUe of 120° The stability conferred

by such cyclic delocalisation also explains why the characteristic

r e g i o n s of aromatic systems are substitutions rather than- the addition reactions that might, from the classical Kekule structures,

be expected and which are indeed realised with non-cyclic conjugated trienes F o r addition would lead t o a product in which delocalisatifea, though still possible, could now involve only four carbon atoms and

would have lost its characteristic cyclic character ( I X ; cf butadiene),

whereas substitution results in the retention of delocalisation essen­tially similar to that in benzene with all that it implies ( X ) :

10

Bonding in Carbon Compounds

In other words, substitution can take place with overall retention of

aromaticity, addition cannot (cf p 102)

A rough estimate of t h e stabilisation conferred on benzene by

delocalisation of its n electrons can be obtained by comparing its

heat of hydrogenation with t h a t of cyclohexene:

I^J| +H S -* +28-8 kcal/mole

+ 3 Ha -j0 +49-8 kcal/mole

T h e heat of hydrogenation of three isolated double bonds (i.e bonds between which there is n o interaction) in such a cyclic system would t h u s b e 2 8 - 8 x 3 = 86-4 kcal/mole But when benzene is hydrogenated only 49*8 kcal/mole are actually evolved T h u s the

i n f r a c t i o n of the IT electrons in beazene m a y be said t o result in the

molecule being stabler by 36-6 kcal/mole t h a n if n o such interaction

took place (the stabilisation ^arising from similar interaction in conjugated dienes is only « 6 Real/mole, hence the preference of

benzene for substitution rather than addition reactions, cf p 102)

This a m o u n t by which benzene is stabilised is referred t o ae«*he

delocalisation energy or, m o r e commonly, the resonance energy The

latter, t h o u g h m o r e widelpused, is a highly unsatisfactory term a s the

v ^ d resonance immediately conjures u p visions of rapid oscillations between one structure and another, for example the Kekuld struc­tures for benzene, thus entirely misrepresenting the actual state of affairs

(vi) Conditions necessary for delocalisation

T h o u g h the delocalisation viewpoint cannot result in this particular confusion of thought, it may lead t o some loss of facility in the actual writing of formulae T h u s while benzene may b e written a s (XI) a s readily as one of the Kekuld structures, the repeated writing of butadiene as (V) becomes tiresome This has led t o the convention

of representing molecules t h a t cannot adequately be written as a single classical structure (e.g (IV)) by a combination of two or more classical structures linked by double-headed a r r o w s ; the way in TVhich one is derived from another by movement of electron pairs

*

often being indicated by curved arrows (e.g (IV) ->-(XII) or (XIII)),

the tail of the curved arrow indicating where an electron pair moves

from and the head where it moves to:

as canonical structures a n d the real, unique structure of the com­

p o u n d , somewhere ' i n between' all of them, being referred to as a

resonance hybrid The term mesoWierism is also used for the pheno­

menon, though less widely, t o avoid the semantic difficulty mentioned above, emphasising t h a t the compound <fbes not have several possible structures which-are rapidly interconverted (i.e it is^jp/

a sort of extra rapid and reversing tautomerism!), but one structure

only, ' i n between' the classical structures t h a t can more readily be written (meso implying ' i n betweea')

A certain number of limitations must be borne in mind, however, whjg considering delocalisation and its representation through two

or m o r e classical structures as above Broadly speaking, the m o r e canonical structures that can be written foj a c o m p o u n d , the greater the delocalisation of electrons and the more stable the compound <qjU

be These structures must not vary t o o widely from each other in energy content, however, or those of higher energy will contribute so little t o the hybrid as t o m a k e their contribution virtually irrelevant Structures involving separation of charge (e.g XII and XIII) may be written but, other things being equal, these are usually of higher energy content than those in which such separation has not taken place (e.g IV), a n d hence contribute correspondingly less t o the hybrid T h e structures written must all contain the same number of paired electrons and the constituent atoms must a l l occupy essentially the same positions relative to each other in each canonical structure

If delocalisation is to be significant, all atoms attached t o unsatur­ated centres must lie in the same plane or nearly so This requirement has already been referred t o for butadiene (p 9 ) , for if the molecule takes u p a position such as (XIV)

12

The Breaking and Forming of Bonds

T h e delocalisation t h a t is so effective in promoting the stability of

aromatic compounds results when there are no partially occupied

orbitals of the same energy The complete filling of such orbitals can

be shown t o occur with 2 + 4 n IT electrons, and (m electrons ( « = 1) is

the arrangement that occurs by far the most commonly in aromatic

compounds lOw electrons (n—2) are present in naphthalene

(delocalisation energy, 6 r kcal/mole) and 147r electrons (n = 3) in

adfnracene a n d phenanthrene (delocalisation energies, 84 and 91 kcal/mole, respectively) and though these substances are not m o n o ­cyclic like benzene, the introduction of the trans-annular bonds t h a t makes them bi- and tri-cyclic, respectively, seems to cause relatively

little perturbation so far as delocalisation of the n electrons over the

cyclic group of ten or fourteen carbon atoms is concerned

A covalent b o n d between two a t o m s can essentially be broken in the -following ways:

THE B R E A K I N G AND FORMING OF BONDS

R : X - » - R :e+ X ® R® + : Xe

Structure, Reactivity and Mechanism »

When a positive charge is carried on carbon the entity is

known as a carbonium ion a n d when a negative charge, a carbanion

T h o u g h such ions may be formed only transiently and be present only in minute concentration, they are nevertheless often of

p a r a m o u n t importance in controlling the reactions in which they participate

In the first case each a t o m separates with one electron leading t o the formation of highly reactive entities called free radicals, owing their

reactivity t o their unpaired electron; this is referred to as homolytic

fission of the b o n d Alternatively, one a t o m may hold on to both

electrons, leaving none for the other, the result in the above case being a negative and a positive ion, respectively Where R and X are not identical, the fission can, of course, take place in either of two ways, as shown above, depending on whether R or X retains the

electron pair Either of these processes is referred t o as heterolytic

fission F o r m a t i o n of a covalent b o n d can, of course, take place by

the reversal of any of these processes^ • Such free radicals or ion pairs are formed transiently as reactive intermediates in a very wide variety of organic reactions as will be shown below Reactions involving radicals tend to occur in the gas phase and in solution in non-polaf solvents and to be catalysed by light and by the addition of other radicals (p 231) Reactions involving ionic intermediates take place m o r e readily in solution in polar solvents

M a n y of these ionic intermediate? can be considered as carrying their charge o n a carbon a t o m , though the ion is often stabilised by de-localisation of the charge, t o a greater or lesser extent, over other carbon atoms o r a t o m s of different elements:

14

Factors affecting Electron-availability in Bonds

FACTORS AFFECTING E L E C T R O N - A V A I L A B I L I T Y IN BONDS AND AT

I N D I V I D U A L ATOMS

In the light of what has been said above, any factors that influence

the relative availability of electrons (the electron density) in particular

bonds o r at particular atoms in a compound will greatly affect its reactivity towards a particular reagent; for a position of high electron availability will be attacked with difficulty if at all by, for example,

® O H , whereas a position of low electron availability is likely t o be attacked with ease, and vice versa with a positively charged reagent

A n u m b e r of such factors have been recognised

• W

(i) Inductive effect

In a covalent single bond between unlike atoms the electron pair

forming the a bond is never shared absolutely equally between the

two a t o m s ; it tends t o be attracted a little m o r e towards the more electronegative a t o m Qj[the t w o T h u s in an alkyl halide

a t o m bonded t o chlorine is itself attached t o further carbon atoms,

tiro effect can be transmitted further:

c—c—c-*-c^-a

The effect of the chlorine a t o m ' s partial appropriation of the elec­

trons of the carbon-chlorine bond is t o leave C t slightly deficient; this it seeks t o rectify by, in turn, appropriating slightly

electron-m o r e t h a n its share of t h e electrons of the a b o n d joining it t o C2,

and so on down the chain The effect of C 1 on C2 is less than the

effect of CI o n C u however, a n d t h e transmission quickly dies away

in a saturated chain, usually being t o o small to be noticeable beyond

Ca

Most atoms and groups attached t o carbon exert such inductive

effects in the same direction as chlorine, i.e they are electron-with­

drawing, owing t o their being more electronegative than carbon, the

major exception being alkyl groups which are electron-donating.*

Though the effect is quantitatively rather small, it is responsible for

the increase in basicity that results when one of the hydrogen atoms

of a m m o n i a is replaced by an alkyl group (p 49), and, in part at any

rate, for the readier substitution of the aromatic nucleus in toluene

than in benzene Several suggestions have been made to account for the

electron-donating abilities of C H3, C H2R , C H R2 and C R3, none of

which is wholly convincing a n d the matter can be said t o be unsettled

All inductive effects are permanent polarisations in the ground

state of the molecule and are therefore manifested in its physical

properties, for example, its dipole m o m e n t •

(ii) Mesomeric or conjugative effect

This is essentially a further statement of the electron redistribution

that can take place in unsaturated and especially in conjugated

systems via their w orbitals A n example is the carbonyl group (p 158)

whose properties are not entirely satisfactorily represented by the

classical formulation (XVII), s o r by the extreme polar structure

(XVIII), that may be derived from it by an electron shift as shown:

* > c — o > c — o

• » (XVII) (XVIII) (XIX)

The actual structure is somewhere in between, i.e a resonance h y b r i d '

of which the above are the canonical forms, perhaps best represented

by (XIX) in which the «• electrons are drawn preferentially towards

oxygen rather than carbon If the carbonyl group is conjugated with

a ^>C=C<^ b o n d , the above polarisation can be transmitted further

* The metal atoms in, for example, lithium alkyls and Grignard reagents,

both of which compounds are largely covalent, are also electron-donating, leading

to negatively polarised carbon atoms in each case: R Li and R —«- Mg- Hal

(cf. p 170)

( •

i 6 n

Factors affecting Electron-availability in Bonds

Delocalisation takes place (XX), so that an electron-deficient a t o m results at C8, as well as at C , as in a simple carbonyl c o m p o u n d The difference between this transmission via a conjugated system and the inductive effect in a saturated system is t h a t here the effect suffers much less diminution by its transmission; C3 is almost as positive

as C x was in (XIX)

T h e stabilisation t h a t can result by delocalisation of a positive or

negative charge in an ion via its n orbitals can be a potent feature in

making the formation of the ion possible in the first place (c/ p 40)

It is, for instance, the stabilisation of the phenoxide ion (XXI) by delocalisation* of its charge \jja the delocalised w orbitals of the nucleus t h a t is largely responsible for the acidity of phenol, i.e the

ease with which it will lose a p r o t o n in the first place (cf p 41):

H

(XXI)

A n apparently similar delocalisation can take place in ciated phenol itself involving an unshared electron pair on the oxygen a t o m I

undime-but this involves separation of charge and will t h u s be correspond­ingly less effective than the stabilisation of the phenoxide ion which does not

Similar stabilisation of the anion with respect t o the neutral mole­cule is n o t shared by benzyl alcohol, which is thus n o more acidic than aliphatic alcohols, for the intervening saturated carbon a t o m pre­

vents interaction with the n orbitals of the nucleus:

and contributes t o its stability but it requires separation of charge and

so will be less effective than that in the carboxylate anion which does not It will be observed that the stabilisation effected in the carboxy­late ion will be particularly marked as the two canonical structures that can be written are of equal energy

The most c o m m o n examples of mesomeric effects are encountered

in substituted aromatic systems: the IT electrons of suitable tuents interact with the delocalised n orbitals of the nucleus and thus

substi-profoundly influence its reactivity, i.e its aromaticity The delocalised

IT orbitals of the benzene nucleus are particularly effective in trans­

mitting the electrical influence of a substituent from one part of the molecule t o a n o t h e r :

18

Factors affecting Electron-availability in Bonds

Thus the nitro group in nitrobenzene lowers the density of nega­tive charge over the nucleus, as compared with benzene itself: it is an

electron-witMrawing group, \f contrast t o the negatively charged

oxygen a t o m in the phenoxide ion (XXI), which is an

electron-donating group Because of the presence of an electron-withdrawing

group, nitrobenzene will be less readily attacked than benzene itself

by positive ions or electron-deficieUt reagents (oxidising agents such

as K M n 04, for example) which, as will be seen below (p 101), are exactly the type of reagents involved in normal aromatic substitution reactions •

Mesomeric, like inductive, effects are permanent polarisations in the ground state of the molecule and are therefore manifested in the physical properties of the compounds in which they occur The essential difference between inductive and mesomeric effects is that

t h e former occur essentially in saturated groups or compound»j*he latter in unsaturated and, especially, conjugated compounds T h e

former involve the electrons in a bonds, the latter those in n b o n d s

^ p d orbitals Inductive effects are transmitted over only quite short distances in saturated chains before dying away, whereas mesomeric effects m a y be transmitted from one end t o the other of quite large

molecules provided t h a t conjugation (i.e delocalised n orbitals) is

present through which they can proceed Either effect influences the behaviour of compounds in b o t h essentially static and dynamic situations: in b o t h the position of equilibria and rates of reaction, in the strength of acids and bases as m u c h as in the reactivity of alkyl halides or the relative ease of substitution of different aromatic species

(iii) Time-variable effects

Some workers have sought t o distinguish between effects such as the two considered above which are permanent polarisations manifested

in the ground state of the molecule a n d changed distributions of

electrons t h a t may result either on the close approach of a reagent or,

more especially, in the transition state, lying between reactants and

products, t h a t may result from its initial attack These time-variable

factors corresponding t o the permanent effects discussed above have

been named the inductomeric and electromeric effects, respectively

Any such effects can be looked upon as polarisabilities rather than as

polarisations, for the distribution of electrons reverts t o that of the

ground state of t h e molecule attacked if either of the reactants is

removed without reaction being allowed t o take place or, if a transi­

tion state is actually formed, it decomposes t o yield the starting

materials again \ * Such time-variable effects, being only temporary, will not, of course,

be reflected in the physical properties of the compounds concerned

It has proved impossible t o distinguish experimentally between

permanent and time-variable effects in a number of cases, but it cannot

be t o o greatly emphasised t h a t despite the difficulties in distinguishing

what proportions of a given effect are due t o permanent and to

time-variable factors, the actual close a p p r o a c h of a reagent m a y have^e

profound effect in enhancing reactivity in a reactant molecule and

as would be expected When, however, the alkyl groups are attached

t o an unsaturated system, e.g a double bond or a benzene nucleus,

this order is found t o be disturbed and in the case of some conjugated

systems actually reversed It thus appears that alkyl groups are

capable, in these circumstances, of giving rise t o electron release by

a mechanism different from the inductive effect and of which methyl

is the most successful exponent This has been explained as proceed­

ing,by an extension of the conjugative or mesomeric effect, delocali­

sation taking place in the following way:

20

Factors affecting Electron-availability in Bonds

H—C-r-H H—C H®

(XXV)

This effect has been called hypercmjugation and has been used suc­

cessfully t o explain a number of otherwise unconnected phenomena

It should be emphasised t h a t it is not suggested t h a t a proton actually becomes free in (XXIV) or (XXV)^for if it moved from its original position one of the conditions necessary for delocalisation to occur would be controverted (p 12)., *

T h e reason for the reversal oi electron-donating ability in going

M e - > E t - > i s o P r - > t - B u is t h a t hyperconjugatioH depends for its operation on hydrogen attached t o carbon atoms a- t o the unijgu-rated system This is clearly at a maximum with M e (XXIV) and non­existent with t-Bu (XXV^I),"provided it is assumed that n o similar

efjf2Ct of comparable magnitude occurs in C—C b o n d s ,

H H®

H- C ^ C H = ^ C H8 ~ H - C = C H - C H8

(XXIV)

compared with isomeric compounds in which it is, i.e (XXIX) in

which there are nine a-hydrogen atoms compared with (XXX) in

which there are only five:

I I

CH 3 —C=CH—CH 3 Me— CH 2 —C=CH 2

(XXIX) (XXX) This leads t o their preferential formation in reactions which could

lead t o either c o m p o u n d on introduction of the double b o n d and

even to the fairly ready isomerisation of the less into the more stable

compound ' '

Although hyperconjugation has proved useful on a number of

occasions, its validity is not universally accepted and a good deal of

further w o r k needs t o be d o n e on, its theoretical justification

S T E R I C EFFECTS

We have t o date been discussing/actors that may influence the rela­

tive availability of electrons in bonds or a t particular atoms in*a

c o m p o u n d , a n d hence influeaQ t h a t c o m p o u n d ' s reactivity T h e

working o r influence of these factors* may, however, be modified or

even nullified by the operation of steric factors; thus effective

delocali-sajjjjp via n orbitals can only take place if the p or n orbitals on the

atoms involved in the delocalisation can become parallel or fairly

nearly so If this is prevented, s i g n i f i ^ n ^ overlapping cannot take

place and delocalisation fails t o occur A good example of thisjjs'r

provided by dimethylaniline (XXXI) and its 2,6-dialkyl derivatives^

e.g (XXXII) The N M e2 group in (XXXI), being electron-donating

(due to the unshared electron pair on nitrogen interacting with the

delocalised «• orbitals of the nucleus), activates the nucleus towards

attack by the diazonium cation P h N8® , i.e towards azb-coupling,

leading t o preferential substitution at o- and, more particularly,

/^-positions (cf p H 9 ) :

(XXXI)

22

^ Steric Effects

T h e 2,6-dimethyl derivative (XXXII) does n o t couple under these conditions, however, despite the fact that the methyl groups that have been introduced are t o o far away for their n o t very considerable bulk t o interfere directly with attack at the />-position T h e failure t o couple at this position is, in fact, d u e t o t h e t w o methyl groups in the o-positions t o t h e N M e2 interfering sterically with t h e t w o methyl groups attached t o nitrogen and so preventing these lying in t h e same

plane as t h e benzene nucleus This means t h a t the p orbitals of nitro­

gen a n d t h e ring carbon atom t o which it is attached are prevented from becoming parallel t o each other a n d their overlapping is thus inhibited.: Electronic interaction with t h e nucleus is thus largely pre­vented and transfer of charge t o the /^-position, with consequent acti­vation t o attack by P h N2 e as in (XXXI), does n o t now take place:

QCXXW)

T h e most c o m m o n steric effect, however, is tfce classical 'steric

h i n d r a n c e ' in,which it is apparently the sheer bulk of groups t h j j is influencing t h e reactivity of a^site in a compound directly a n d n o t by p r o m o t i n g o r inhibiting ^ectrbn-availability This h a s been investi-

:-Wted closely in connection with the stability of the complexes formed

%y trimethylboron with a wide variety of amines Thus t h e complex

(XXXIII) formed with triethylamine dissociates extremely readily whereas t h e complex (XXXIV) with quinuclidine, which can b e looked u p o n as h a v i n g ^ i r e e ethyl groups o n nitrogen that are 'held

b a c k ' from interfering sterically with attack on the nitrogen a t o m ,

/ \ e 0 /

CH , N : B—Me

\ C H2- C H2^ \ CH2"~CHf2 Me

(XXXIV)

T h a t this difference is n o t due to differing electron availability a t the nitrogen a t o m in the two cases is confirmed by the fact t h a t the two

amines differ very little in their strengths as bases (cf p 56): t h e uptake

of a p r o t o n constituting very much less of a steric obstacle than the

u p t a k e of the relatively bulky B M e3

M o r e familiar examples of steric inhibition, however, are probably the difficulties met with in esterifying tertiary acids (XXXV) and 2,6-disubstituted benzoic acids (XXXVIa)

R3C C O , H

(XXXV)

and then in the hydrolysis of the-esters, or other derivatives such as amides, once m a d e T h a t this effect is indeed steric is suggested by its being much greater in magnitude t h a n can be accounted for by any influence the alkyl substituents might be expected t o have on electron availability and also by its non-occurrence in the aromatic species if

t h ^ ^ u b s t i t u e n t s are in the m- or /^-positions Further, if the carboxyl

group is moved away from the nucleus by the introduction of a C H2

group, the new acid (XXXVI6) may now bqjesterified as readily as the unsubstituted species: the functional group is now beyond the steric range of the methyl substituents

It should be emphasised t h a t s u c h steric inhibition is only an extreme case and any factors which disturb or inhibit a particular orientation of the reactants with respect t o each other, short of pre­venting their close approach, can also profoundly affect the rate of reactions: a state of affairs that is often encountered in reactions in biological systems

electron-24

Classification of Reagents

etc

(XXXVII) will tend t o be most readily attacked by positively charged ions such

as P b N2 e, ^ h e diazonium cation, or by other species which, though

not actually ions t h e m s e l v « , possess an a t o m or centre which is

electron-deficient, for example the sulphur a t o m in sulphur trioxide:

Oe

A

*Azo-coupling (p 112) or sulphonation (p 108) takes place on a

carbon a t o m of the nucleus rather than on oxygen because of the

charge-transfer from oxygen to«carbon t h a t can take place as shown

above and because of the greater stability of the carbon rather than the

as ®OH, eC N , etc., or by other species which, though not actually

ions themselves, possess an a t o m or centre which is electron-rich, for

example the nitrogen a t o m in ammonia or amines, H3N : or R3N :

It must be emphasised that only a slightly unsymmetrical distribution

of electrons is required for a reaction's course t o be d o m i n a t e d : the

presence of a full-blown charge on a reactant certainly helps matters

along but is far.from being essential Indeed the requisite unsymmetri­

cal charge distribution may be induced by the mutual polarisation of

readily react An electron-rich c o m p o u n d , such as phenoxide ion,

(XXXVII)

Structure, Reactivity and Mechanism ^

reagent and substrate on their close approach as when bromine adds

t o ethylene (p 137)

In reactions of the first type the reagent is looking for a position

in the substrate t o be attacked where electrons are especially readily

available; such reagents are thus referred t o as electrophilic reagents or

electrophiles In reactions of the second type the reagent is looking for

a position where the atomic nucleus is short of its normal complement

of orbital electrons and is anxious t o m a k e it u p ; the reagents employed

are thus referred to as nucleophilic reagents or nucleophiles

This differentiation can be looked u p o n as a special case of the acid/base idea The classical definition oV acids and bases^s t h a t the

former are proton-donors and the latter proton-acceptors This was

made more general by Lewis w h o defined acids as compounds pre­

pared t o accept electron pairs and bases as substances that could p r o ­

vide such pairs This would include a number of compounds not pre­

viously thought of as acids and bases, e.g boronJtrifluoride (XXXIX)

F Me F Me _

\ / \ e • / F—B + :N—Me ^ F—B:N—Me

• / \ * / \

F Me " F Me (XjftCIX) (XL) j which acts as an acid by accepting the electron pair on nitrogen in

trimethylamine t o form the complex (XL), and is therefore referred

to as a Lewis acid Electrophiles and nucleophiles in organic reactions^

can be looked u p o n essentially as acceptors and donors, respectively,

of electron pairs from and t o other atoms, most frequently carbon

Electrophiles a n d nucleophiles also, of course, bear a relationship to*

oxidising and reducing agents for the former can be looked u p o n as

electron-acceptors and the latter as electron-donors A n u m b e r of the

more c o m m o n electrophiles and nucleophiles are listed below

of the former on the latter is a nucleophilic attack, while that of the

"fatter on the former would be looked u p o n as an electrophilic a t t a c k ; but from the standpoint of whichever reactant a reaction itself is viewed, its essential nature is not for a m o m e n t in doubt

It should n o t be forgotten, however, t h a t reaetions involving free radicals as the reactive entities are also known These a r e m u a b less susceptible t o variations in electron density in t h e substrate than are reactions involving p o l a j intermediates, but they are greatly affected

by the addition of small traces of substances t h a t either liberate or

remove radicals' They are considered in detail below (p 240)

+ ®NO, + H®

In nucleophilic substitution reactions, it is often an a t o m other than

hydrogen that is displaced (pp 58, 132):

H , T l O

i N 02 T N Os

1 + H 0

though hydride ion is not actually liberated as such as will be seen

subsequently (p 131) Radical-induced displacement reactions are also""

known, for example the halogenation of alkanes (cf p 248)

Addition reactions, t o o , can be electrophilic, nucleophilic or

radical-induced depending on whether the process is initiated by ah

electrophile, a nucleophile or a radical Addition t o simple c a r b o n

-carbon double bonds is normally either an electrophilic or radical

reaction; an example is the addition of H B r

HBr

Br

H which can be initiated by the attack of either He (p 141) or Br • (p 244)

on the double bond By contrast, the addition reactions exhibited by

28

displaced, classical aromatic substitution (p 101) being a good

example:

CN Elimination reactions are, of course, essentially the reversal of addition reactions; the mosU^ommon is the loss of a t o m s or groups from adjacent carbon atoms t o yield defines:

Rearrangements m a y also proceed via electrophilic, nucleophilic

or radical intermediates and can involve either the mere migration of

a functional group (p 86) as in the allylic system

or the actual rearrangement of the carbon skeleton of a compound as

in the pinacol (XLII) ->pinacolone (XLI1I) change (p 90):

the carbonyl group in simple aldehydes and ketones are usually nucleophilic in character (p 158) A n example is the base-catalysed formation of cyanhydrins in liquid H C N :