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ORSANIC CHEI.IISTRY I F1l >

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UNLV PUBL
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Due to the customization of this course pack, it is non-refundable.

 Organic Chemistry I
Y

CHEM 241-L
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Pradip K. Bhowmik
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 ORGANIC GHEMISTRY I
Dr. Pradip K. Bhowmik and Dr. Haesook Han

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To those who are willing to learn organic chemistry
 PREFACE

As we know it, learning organic chemistry for the undergraduate students is an

enormously difficult anO a paintultask, since organic chemistry covers a bewildering
number of brganic reactions, millions of organic compounds, and hundreds of reagents.
To the studeits, it seems impossible (not quite right!) to learn this enormously vast
knowledge of organic chemistry that has been developed over a period of 200 years. A
litle effol is being made to facllitate the learning of organic chemistry by students who
neecl a basic understanding of the subject to support study in their chosen fields,
whatever they might be. The approach we have taken in this book is to limit the content
and present only ihat which is essential for the student's understanding the
fundamentals oi organic chemistry. This approach is designed to encourage a thorough
understanding of thL subject as opposed to rote memorization. We hope to seek the
following outctmes for students using Organic Ghemistry I:

r A limited but effective knowledge of organic chemistry and the relationships

between different classes of organic compounds

o An ability to comprehend basic information about organic compounds and their

reactions that include mechanisms, various intermediates and various reagents

. An ability to master the knowledge necessary for the multistep organic synthesis
for a target molecule by using principal organic reactions

An important piece of advice to the student is that there is no shortcut in learning organic
chemistry, Uui to say PRAGTICE! PRACTICE! And PRACTICE! ORGANIC
cHEMtSTRy tS FUil! cOOD LUcK To STUDENTS WHO ARE TRYING TO LEARN
ORGANIC CHEMISTRY! Any comments or suggestions for the improvement of this
book are most welcome. Oui effort is worthwhile if student discovers that this book is
beneficialto them. Last but not the least, thanks are due to Alexi K. Nedeltchev for the
compilation of all the chapters with figures and tables in this book.

Pradip K. Bhowmik and Haesook Han/June 16, 2003

ilt
 CONTENTS

Chapter 1 Structure and Bonding 1

Chapter 2 Polar Bonds and Their Consequences I

Chapter 3 Organic Compounds: Alkanes and Cycloalkanes 13

Chapter 4 Stereochemistry of Alkanes and Cycloalkanes 25

Chaper 5 An Overview of Organic Reactions 33

Chapter 6 Alkenes: Structure and Reactivity 41

Chapter 7 Alkenes: Reactions and Synthesis 57

Chapter 8 Alkynes: An lntroduction to Organic Synthesis 68

Chapter 9 Stereochemistry 83

Chapter 10 Alkyl Halides 91

Chapter 11 Reactions of Alkyl halides: Nucleophilic Substitutions 100

and Eliminations

Chapter 14 Conjugated Dienes and Ultraviolet Spectroscopy 130

Chapter 15 Benzene and Aromaticity 139

Chapter 16 Chemistry of Benzene: Electrophilic Aromatic Substitution 145

IV
 Chapter 1 Structure and Bonding

is the study of carbon compounds. This element alone, among

allof
organic chemistry
diversity of
the elements (109) in the periodic table, is able to form an immensely
acid) with tens
compounds. Methane with one carbon (cHo) and DNA (deo>qrribonucleic
of Oiition of atoms are two examples of organic compounds.
(+) and neutrons
Atoms: An atom consists of a positively charged nucleus [protons
(Z) is the mass of
(neutral)l surrounded by one or more electrons (-). Atomic weight
Atomic
protons and neutrons in tne nucleus, since eleciron has a negligible mass'
the number of protons in the- nucleus or the number of
number (A) is equai'io
"itn"t
electrons around the nucleus. Atomic radiusfor H is = O'37 and that for C = O]7 Al1 A
ml. The electron configuration of an atom describes the
i*gr,r"',) = f otr cm = 10-10various orbitals also called atomic orbitals. The probable
arrangement of electrons in
is called orlcital'
location of any electron relative to the nucleus with a particular energy
and different shapes. For examples, s
Different orbitals have different energy levels
The electronic configuration of
orloitals are spherical and p orbitals are dumbbell-shaped.
proper orbitals, beginning with the
any atom is written by issigning electrons to the
lowest energy.

Table 1. Electron configurations of 10 elements

Element Atomic Number Electron Confi guration

H 1 1s'
He 2 1s2
Li 3 1s2 2s1
Be 4 1s22s2
B 5 1s2 2s2 2p1
c 6 1s2 2s2 2p2
N 7 1s2 2s2 2p3
o I 1s2 2s22p4
F I 1s2 2s22p5
Ne 10 1s2 2s22pG
c(6) ,f LL- N(7) ,r'LJ--j-
2? .lL 2s2 JL
1f JL ls 1s2 -jL ls

o(8) ,p^ ][-LL F(e) ,o'LL1-

z? -lL zJ JL
rJ -jL lr 1s2 ]L lr
o
1s
o
2s
CO
2P*
B
2pv
I
2p,

Compounds: They are made of various atoms. Every atom has a unique property to
combine with other atoms to form compounds. The combining capacity of an atom is
called valency and is determined by valence electron(s). For example, carlcon valence
electron is 4, nitrogen valence electron is 5, and halogen valence electron is 7-

aaaa' aaa
f{o .O. .N. .C. 3F. .B.
aa
"t'

Govalent Compounds are formed when electron pairs are shared between various
atoms. These representations of chemical structures are called Lewis structures.
Simpler, however, is the line-bond structures, in which a two-electron covalent bond
is
inOiiateO as a Iine drawn between two atoms. Valence electrons that are not used for
oonoing are calted nonbonding electrons, or lone-pair electrons. Many organic
compolnds are covalent comfounds. These compounds are usually not soluble in
,rt"r, but soluble in organic solvents (e.g., hexane, chloroform, alcohols). They have
relatively low melting p6ints (in the casesof solids) or low boiling points (in the cases of
liquids). H
....1
fl..fi.rfl flrrirlrofl ]{orfor}l
; ; ;i
'"!33C"H

,-Q-, ,-T-, H

-^/^
-'\,
H
lonic Compounds consist of positive and negative ions (e.9. NaCl) that hold them
through electrostatic interactions. Positive ions are formed from the loss of electron or
electrons from electropositive atoms and negative ions are formed from the gain of
electron or electrons from electronegative (electron greedy) atoms. These compounds
are usually soluble in water, but not soluble in organic solvents. They have relatively
high melting points or high boiling points.
-le -.@ .- ^,
5a (10)
Na(11)+
,i. (r) +te , ,fr'31roy
NaF is an ionic compound. Similarly CaF2, KCI and KBr are ionic compounds.

Coordination Gompounds are formed when electron pair from a given atom share with
another atom (or ion) to form a chemical bond. For example, [Cu(H2O)s]'* is a blue
colored compound. They are typically colored and consist of transition metal ions and
various ligands. Ligands are either negatively charged species or neutral molecules that
contain atoms having lone pair of electrons.

3NH3
OH,
a\
6n, ..1..
''*\
')+
).,./*'
*x/ I \^,,
Cu

/
aa \.. \
HrO -aa
oH"
aa I
3NH3

[Co(]tH3)613+

Hybridization of Orbitals: Lewis structures do not indicate the shapes (geometry) of

covalent compounds. ln order to get an idea of the shapes (three dimensional) of
organic molecules or other molecules as well to understand chemical structures of
miilions of organic compounds, hybridization (mixing of atomic orbitals) is an important
concept in organic chemistry. Simply, hybrid orbitals form stronger bonds than the
unhvb,ndized or individual orbitals. Carbon uses three different types of hybridization
(sp', sp'and sp). By using these hybrid orbitals carbon can form over 18 million organic
compounds.

o'l +
rp3 nyUria orUitats

J
 x.2, ,b('\ u
*\,*^ l{* - oft r-'$er lcrP
[ra c,d
$'-r
-\/
s-
1f t-t
\{*
H t
r-t
rf bt *rC
csA ,orra\
,df-\- 4ry = *P'

Tetrahedral
H

..$,
VU
H- ,H
,=Xlo+"
o tH
,'o

in CHa, CzHe etc'

lf carbon uses sp3 hybrid orbitals, it forms 4o bonds as
orbital
,/*frndizedP

O1 +

3o bonds and 1n bonds as in

lf carbon uses sp2 hybrid orlcitals in bonding, it forms
ethylene.
 {r'ffiybidizrudPorbital

O1 + 4
Itnro" ht:*-tC
1&u "
sp hybrid orbitals

HLc+c oH
b
?r+AaY : eP
bonds and2n bonds'
lf carbon uses sp hybrid orbitals in bonding, it forms 2o
ln covalent bonding of organic compoundicarbon ,r",
on" of inree hybrid orbitals (sp3'
in covalent
;i;;Jgpf Sirn"rrv, niiog"n and o}ygen also use the hvbrid orbitals
bonding.

Ott +
2s

N (rp' hybrid orbitals)

hYbtid orbital
t r/'n*P'

in one of the hybrid orbitals (sp3)'

Notice that lone pair of electrons of nitrogen resides
 Olt +
2s

O (rp'hybrid orbitals)

orbital
,4'"tP'hYbtid
x.f
#,_. -1

Notice that two lone pairs of electrons reside in two of the hybrid orbitals (sp3).

(This carbon is bonded with 3o bonds and ln bond)

f' f
HrC:g-CHz
A
l
I
sP (Since this carbon has 2o bonds and2n bonds)

Molecutar Formula represents the number of various atoms present in a molecule. For
example, molecular formula CaHa is an organic molecule.
ln drawing line-bond structures for organic molecules, carbon has four bonds, nitrogen
has three bonds and one lone pair of electrons, oxygen has two bonds and two lone pair
of electrons, halogen has one bond and three lone pair of electrons, and hydrogen has
one bond.
g|tucture J(spr*u'to . [ru-.o a*r"rfis #rr*' dlr'Y'$u1.3"e t]

1-i
cIll ,, u \-\
yl
\-\ F1

*r I t

li ur *u*{""*1--}
\-\ -ctl -L- D- H
I

\{ lJ
r

rl!l t-i

$rer*ur*rl 6'(' -...----z' .la:

r"*",gtitu*u-xr*x'l 'tr rn'\"111'
*AY,w-"r*'r $flP't{ .\f&"rcq* i;ql 'tt
] ;;,:f-:5*
 HHH
lllc-c-H
CrHs
lll
HHH
HH
ll
H-C-C-N-H
CrHzN
lll
HHH
HH
ll
CzrLQ
ll
H-C-C-O-H

HH
H
CzHaQ
lll
H-C-C-HI
'O,

H/c\
o:
/\,,^
"-,
I
H H

lll
HHH

C-C-Br:
C3H7Br
tll
HHH

HHHH
llll rlll
HHHH

csHeN H-C-
HHH
rll N-H H-C-C-N-C-H
lll
HH
HHH

H-C-C-N-H
tll
H

ll N-C.-H

H
ll-C-H H
ll\, -C-H
,/l "/l
H

ln converting a molecular formula to line-bond structures, one must examine all possible
structures consistent with the rules of valence. One must systematically consider all
possible attachments, including those that have branches, rings, and multiple bonds
(double and triple bonds).
 Chapter 2 Polar Bonds and Their Consequences

Polar Covalent Bonds. Many organic compounds contain polar covalent bond(s) as a
result of unsymmetrical electron sharing caused by differences in the electronegativity
(electron greedy) of atoms. The list of electronegative atoms is as follows.

c (2.5) N (3.0) O (3.5) F (4.0) <-**+ +--> hrn;xclor

si (1.8) P (2.1) S (2.s) Cl (3.0) ,^- r
(- r\
Br (2.8) .Ul
-.
r(2.5)
t+tr :_r!truclt' J.J=o

u,dl,
T- ,/ Net

*'f-" H
.l+
CK
U+
,,--f-k.*
(Polar P=l.87 D) fuolar p=1.85 D) (polar yl.a7 D)
1i 1u*\l^'1
H :--#:r ,tt,
,-,.cE l- e;1w'J-
'"'r""..'jt{i" t1

* 6, i\,,
*{-,
(nonpolar Ir:0 D) OooPof* P=0 D) H

(nonpolar p=0 D)

Formal Charges. Many organic compounds contain formal charges 1+ and - or 2* or 2'
etc.) to specific atoms within molecules. Specifically, atoms (within molecules) having
apparently "abnormal" number of bonds have formal charges. lt can be calculated by
using the following formula:
Formal Charge = # of valence electrons -%(# of bonding electrons) -# of nonbonding
electrons. lrne t_) .i"+ (..)
Here is the list of few molecules that contain formal charges.
 ,H
,-i{; lt E:9'OP
H3c-l-H
H
I
H

:o:

Hac-c-9t
11.."@
Na

Resonance. Many chemical structures for organic compounds cannot be accurately

represented by single line-bonds formulae. These organic compounds have more than
one chemical structure. All of these structures arise because of delocalization of n-
electrons and/or lone pair(s) of electrons.

For example, benzene is a resonance hybrid of the two structures (l and ll), which are -- O z-

structures.
1

called resonance i t.
I

*i
I

L ,\_ I

Na2CO3 (three resonance tructures axe as follows) lO", ()l

I
1

..o I

'l"p ,6? :o: J

<+
I I
I I

*Bgol"sr" QP"q, .y'c--51

- ffw L-t"b'lr",d kd+'
Three major rules for drawing resonance structures for organic compounds are as
follows.

1. Only n-electrons or lone pair(s) of electrons (not o-electrons or nuclei of various

atoms) may be shifted, and they may be shifted to adjacent atoms or bond positions.

2. Resonance structures in which an atom (the period-2 elements) canies more than
eight electrons (octet rule) are not contributors to the real structure.

3. The more important resonance structures show each atom with a complete octet and
as little charge separation as possible.
Why is resonance important in organic chemistry?
It can explain many chemical phenomena in organic chemistry.
ln benzene molecule all carbon-carbon bond lengths are of equal length because of
resonance. ln sodium carbonate all three carbon-oxygen bonds are of equal length
again because of resonance (shown above).
It also can explain why carboxylic acids are organic acids. For example, acetic acid
(CH3COOH) is a carboxylic acid because its conjugate base acetate ion is a resonance

'iD,*
stabilized as shown below:

'it
H3C-CIO; <:-+ H.C-C:9 =

It can explain why phenols are more acidic than alcohols. Phenol is more acidic than
alcohol because its conjugate base phenoxide ion is a resonance stabilized in contrast
to alkoxide ion, which has no resonance structure.
-@

€*$, -*+<+&**d
A few resonance structures of organic compounds (or species) for practice:

,(r:*eo<-+Q
o) H2c-cr- <---> nr"G-8n-*- cH- cH3
"r4)Bn- "r. A
I
V
(D
H2C-69:CH-CH-CH-CH3

ffi\
w €

(d) Hrf}Rfh" eJ1

<:-------> H2C-NE[tl:
9-@
€H2C-N:1r1:

10
Acids and Bases. They are defined on the basis of two concepts.
(1) Bronsted-Lowry definition. Acids are proton donors and bases are proton
acceptors. The name proton is often used as a synonym for H*, because loss of valence
electron from a neutral hydrogen atom leaves only the hydrogen nucleus that contains a
proton only. Acid strengths are measured by using pK. values rather than G values.

pKu: Jog Ku Ku:

Ir,o"]lf I

[*l
A stronger acid (larger K) has a smaller p(, and a weaker acid (smaller l() has a
larger pl(. For example, HzO (pl(" = 15.74), phenol (pG = 9.89), HzCOs (p& = 6.37)
CH3COOH (pG = 4.76) and HCI (pG = -7.0). Therefore, the increasing acid strength for
these compounds is as follows:

H2O, Phenof H2CO3, CH3COOH, HCI

Remember! Acid strengths of various compounds are always relative.

Remember! There is an inverse relationship between the acid strength of an acid and
the base strength of its conjugate base. The species that is left over after donation of
proton is called conjugate base, and the species that is formed after accepting a proton
is called conjugate acid. The stronger the acid, the weaker the conjugate base and vice
versa.

o
@o.. lt
CH3COOH + trti i0tt n.".zb--6pt*" + HzQ
acid base coniugat" buse conjugate acid
-
A strong acid is one that loses an H* easily, meaning that its conjugate base has little
affinity (attraction) for the H* and is therefore a weak base. A weak acid is one that loses
an H* with difficulty, meaning that its conjugate base has a high affinity (attraction) for
the H* and is therefore a strong base. The fact that HCI is a strong acid, for example,
means that conjugate base Cl- does not hold H* tightly and is thus a weak base. Water,
however, is a weak acid; meaning that its conjugate base hydroxide ion does hold the H"
tightly and is a strong base. Therefore, the increasing base strength for the following
compounds is as follows:
NaCl, CH3COON4 NaI{CO3, NOH

ln other words, among these compounds -OH is the strongest base and chloride ion is
the weakest base. -HCOg is a weaker base than -OH but stronger than CHaCOO-. By
using this weak base (-HCO3), one can be able to identify phenol (pK" = 9.89) and acetic
acid (pG = 4.76) as unknowns. The bicarbonate being a weak base, it will react with
acetic acid to produce COz and water, but not with weak acid phenol. The complete acid-
base reaction is as follows:

ll
 cftcooH + Nallcq -+ cn coS@Nu + corf + Hzo
By using this bicarbonate weak base, one would be able to separate acetic acid and
phenol from their mixtures.
(2) Lewis Acids and Bases. Lewis acids (having low-energy empty orbital) are electron
pair acceptors and Lewis bases are electron pair donors. For example, BF3, AlCls and H*
are Lewis acids. NHa and HzO are examples of Lewis bases. Most organic molecules
that contain oxygen and nitrogen having lone pair of electron(s) are Lewis bases.
f
H(aa- 9- H*'Cl'
{/r
-g
Ct + ;6-H
I
-+
FF
i_ I

,_|ft cHg.-+ F-F-B-"*,

i I
F CHs
ll
F CHs

Cl tClt

1""'\
",-|4., 'cn.
-
*tJ^,.-+, e,- l-R4:-.
I \^..
I cl ,1,, cHs

I* t'-
t-
rI,^ t-r.

D * i"t"trt
I -e-#**-=\
f-rr. {.:
ItJ + : **+ l- *
i-)
lr, -(
rl
.\ ) *. r^u
r-t'_)
t
I
tt
F
cil* F .Li
u_, lx
J
-13
,) Zp!--f* r t Lr'*,re
zsM -\t/ --;,-,1,r,''*
*Y
tstg =p'

72
 Chapter 3 Organic Compounds: Alkanes and Cycloalkanes

There are more than 18 million known organic compounds. Each of these compounds
has its own physical properties, such as melting and boiling points, and each has its own
chemical reactivity. The structural features that are responsible for the classification of
organic compounds by reactivity are called functional groups. A functional group is an
atom or group of atoms within a small or large molecule that has a characteristic
chemical behavior (or reactivity). The chemistry of every organic molecule, regardless of
its size and complexity, is determined by the functional group it contains. Table 3.1
contains a list of functional groups for various organic compounds that are very
important in leaming organic chemistry!
ln leaming functional groups, one looks at the connectivity of various atoms (typically 2
or 3 or 4 ---atoms) that make up the various functional groups. For example, when -OH
(hydro><yl) group is connected to an spt-C atom, it is called alcohol. Alcohols are a class
of organic compounds that contain numerous alcohols includin^g cholesterol. When it is
connected to an aromatic ring (that typically consists of six sp2-C atoms to form a cyclic
structure), it is called phenot. Siinitarti, when N atom is connected singly to an sp3-C
atom, it is called an amine. When N atom is singly bonded to an sp2-C atom that is in
tum doubly bonded to o>rygen atom, it is called an amide fCONH2). When carbon is
doubly bonded to an oxygen atom, it is called a carbonyl group. This group is very
important, since it is present in many functional groups, such as aldehyde (-CHO),
ketone CCO-), carboxylic acid (-COOH), acid halide CCOX), acid anhydride [(-
CO)zOl, amide CCONH2) and ester (-COOCH3). The connectivity difference between an
aldehyde and a ketone is that the former contains a carbonyl group that is connected to
an H atom and the latter contains a carbonyl group that is connected to other carbon
atoms (either sp2 or sp31. They are two different classes of organic compounds. The
classes of organic compounds that contain doubly bonded carbon atoms (sp'-C atoms)
and triply bonded carbon atoms (sp-C atoms) are known as alkenes and alkynes,
respectively. Another class of organic compounds, which contains o)rygen atom that is
singly bonded two carbon atoms, is called ether (C-O-C). When carbon atom is
connected to a halogen in many compounds, it is called organic halide.
One can also classify alcohols, organic halides, amines, and amides into three groups
what are called 1' (primary), 2o (secondary), and 3" (tertiary). Examples are shown in
Table 3.2.

13
Family Functional group
n{rne strugture" Simplo example Name euding

Alkane (Contains only C-H and clrscHs -ane

C-C single bonds) Ethane
\/
Afkene C:C H2C:CH2 'ene
/\ Ethene (Ethylene)
Alkyne -C=C- H-C=C-H 'yne
Ethyne (Acetylene)

Arene HH
\ / \/ None
C:C
_C/\ C- H-C.
/t:c\ .C-H Benzene

\\/C_C \/
C-C
/\ /\
t.. HH
Irsc-cl
Halirle
-c-x:
t" None
Chloromethane
(X = tr', Cl" Br, I)
t.. H3C-O-H
-c-o-H
l" -ol
Methanol
t..t
-c-o-c-
l"l H3C-O-CHs ether
Dimethyl ether
t..1..
-f -T-*'-?-I-',, H3C-NHz -arnine
Methylamine
H
t..
tl
-C-N_
I
Nitrile -C-C=N: HsC-C=N -nitri,le
I Ethanenitrilq (Acetonitrile)
:o: o
| *// *//
Nitro HsC-\
t\
-C-N
' :O:- \
o-
None
Nibomethane

l..t
_C-S-C_ HsC-S-CH3 sulfi.de
t"l Dimethylsulfide
:d; o-
ll*l I

Sulfoxide
-c-s-c-
t"l
HsC-sa-CHg sulforidc
Dimethyl sulfoxide

I4
 tr'unctional grrup
structur"er Simple example Name garling

:o: o-
Sulfone
ttl
_C-S,iC-
I
HsC- $oCn, sulfone
lt_l
,9, o-
I Dimethyl sulfone

Thiol
t.. Ir3c-sH -thiol
-C-S*Ht" Methanethiol
:o:
iI
Carbonyl,
-C-
o
lr
Aldehyde H3C-C-H -al
Ethanal (Acetalilehyde)
o
il
Ke,tone HsC-C*CH3 -ofle
Propanone (Acetone)
o
tl
Carboxylic H3C*C*OH -oic ocid,
acid Ethanoic acid (Acetic acid)
o
tl
Esier HsC-C-O-CHe -odte
Methyl ethanoate (Methyl acetate)
o
ll
Amide HsC-C-NHz -a.nz.idc
f, ftfu anarnifl g (Acetamide)

o
Carboxylic
acid IIsC- C
lt,--Ct -ayl chloridc
Ethanoyl chloride
clloride (Acetyl ehloride)
::O:, :O: oo
carboxylic I
acid
i ll ll I ilil
H3C-C-O-C-CH3
-oic onhydri.dz
Ethaaoic anhydriile
anhydride-C*C-O-C-C-
I I -" I (Acetic anhydride)

tIld
bonds whose connectioDs aren't sp€dned are a;sEmed fu be attached to carbon m hydmgon atome in the rest of tho
mdecde.

15
 3.2 Various Types of alcohols, organic halides, amines and amides

Alcohols:
H
\ -a'+"Cl
\ /r'
relt
\ .,J.
-
I
" I
I
HaCHcCi-

lo
IF\
v-l H

zll l" crl.olrul (1)

f ntc*:h,el
Organic halides:
[a:rj,,yr"., T l,or;clc
H
ga\\'H l J
" I
T"
H3cH2c-i-x -l
H2C-C-X
I
H3c-T-x
I I
H cHs CHs
(1) lr.li'lt (2") f ,.l'..lt.-: (3") l',*l'cle:
Amines:

H"iL*. ",.'-TY'r"
I."-T-'.c[s r]'

tv1
R .-lri n'
(3") 6r"r'L
(1o) o*,,ne
ffi
Amides:
o
,/--_l\ll
Qsc]-c-NHz
r't ll
, H.g-[-T-cH. .. ry,' .H.c-[-N-CH",
--\, ll , " l*r I

!:
(lo) a.' ', r\e (2o),",1,.b ,r.J,,,,,,,8:,,' o'

ALKANES are called saturated hydrocarbons because they contain only carbon and
hydrogen; saturated because they have only C-C and C-H bonds and thus contain the
maximum possible number of hydrogen atoms per carbon atom. The general formula of
alkanes is GnHar*2, where n is an integer. CHa, CzHe and CgHa are known as methane,
ethane and propane, respectively. They are the first three members of alkanes for each
of which there is no possible isomer. As one increases the number of carbon atoms, the
number of compounds increases because of different connectivities of carbon and
hydrogen atoms for alkanes. For example, CaHls have two different structures (n-butane
and isobutane shown below). The chemical structures that have the identical molecular
formula but different structures are called simply isomers or constitutional isomers.
lsomers are compounds that have the same numbers and kinds of atoms but differ in the
way the atoms are arranged. ln the following example, n-butane (where n denotes

16
 atoms
normal or straight-chain) and isobutane are constitutional isomers, because their
are connected differentlY.

TTIT H..'\/' V,
IIII
c-c-c-c-H or

')"-x
(n-butane, CaHro) HsC-CHz-CHz-CHa [CH3CH2CHzCHg or HaC(CHz)zCHs]

(lsobutane, CaHro, 2-methylpropane)

CH. HsC-9H-CHg
l-
,o.
I
I

H3C-CH-CHs cHs

All of these structures of n-butane and isobutane arise because the free rotation of C-C
bond occurs at room temperature very easily.

Molecular Formula # of isomers

CHa (Methane) 1

CzHs (Ethane) 1

CsHa (ProPane) 1

CrHro (Butane) 2
CsHrz (Pentane) 3
CsHra (Hexane) 5
CzHre (HePtane) 9
CaHra (Octane) 18
CgHzo (Nonane) 35
CroHzz (Decane) 75

CrsHsz (Pentadecane) 4,347

throughout
Constitutional isomerism is not limited to alkanes only, but it occurs widely
and
tne organic chemistry. They may have different carbon skeletons (as in n-butane
isobutlne), differentiunctionalgroups (as in ethyl alcoholand dimethylether), or
ditferent locations of a functionil group (as in n-propylamine and isopropylamine)'
ditferent
negarOless of the reason for the iiomerism, constitutional isomers are always
points, boiling points,
coripounds with different physical properties (that is, melting
shows
density, and refractive indices), but with the same molecular formula. Table 3-3
three typ"t of constitutional isomers of various organic compounds.

L7
Table 3.3 Different Types of Constitutional Isomers (or Isomers)

Different carbon skeletons

CHe

I
C+Hro H3C-cH-CH3 CH3CH2CH2CH3

Isobutane n-Butane

Different fu nctional groups

czHog cH3cH20H cH.-9-cHs

Ethyl alcohol Dimethyl ether

Different position of functional Oo"n,

i*,
C3HeN, H3C-cH-CH3
t" CH3CH2CH2NH2

Isopropylamine n-Propylamine

(a) Constitutional isomers of a ketone having molecular formula CsHlgO.

ll llt
t
il
:O, :O I tO CHS

H3C-CH 2-C-CH2CH3 HgC-C-CH2CH2CH3 H.C-6-CH-CH3

(b) Constitutional isomers of an aldehyde having molecular formula C5HI6O.

:O' rO:

ll il
CH3CH2CH2CH2-C-H H3C-CH2-CH-
I
I
CHs

:o,
CHq :O:
H3C-CHCHT-g-6
il
l"ll
H3C-C-C-H
I I
cHa I
CHr

t8
(c) Constitutional isomers of an amine having molecular formula CsHr:N. (Total 17 isomers)

crucH2cH2cH2cH2NH2 HeC-CH-CH2CH2[\IH2
"l H3CH2C-CH-CH2t\iH2
'i
rl
cHs cHg

CHa rNH,
cH3cH2cH2cHNH2
l-
t..l t'
I H3C-9-CH2NH2 CH3CH2CHCH2CH3
I
cHs I
cHg

:NH, :NH"

"l
H3C-CH-CH-CH3
t" H3GH2C-9-CHs
t' (1o amine)
I
cHe cHs

H
ll
H CHs
I
I
H3CH2C-N-CH2CH2CH3 H3CH2C-N-cH-CH3

H H

I I
cH3cH2cH2cH2-N-cH3 H3C-CH-CH2-N-CH3
t-
I
cHs

CH"
t"l
H H
I

--l
I
HsC- c-N-cHa CHeCHzCH-N-CH3 (2o amine)

I I
cHs cHs

s"6_ij i"
,."-l-cH-cH3
H3CH2C-N-CH2CH3
I
"t -cH2cH2cH3
I I
CHs c H3 cHs
(3'amine)

19
ALKYL Groups. lf an H atom is removed from an alkane, the partial structure that
remains is called an alkyl group. As such alkyl groups are non-eistent themselves; they
are simply parts of large compounds. They are generally represented by R (Rest of the
molecule).

Struchre Name Structure Name

CHe- CH.
methyl
t-
I
H3C-CH-CH2- isobutyl
CH3CH2- ethyl

cH3cH2cH2 n-propyl H.C-Cij,-CH- sec-butyl

I (secondary-butyl)
I
H,C cHs

cH- isopropyl

*r/
CH3CH2CH2CH2- n-butyl
"l
HrC-C
T*'
tert-butyl
(te rtiary-butyl)
CHe
ln a given organic compound, one can easily find various types of carbon atoms what
are known as 1o, 2o, 3o , and 40 C (carbon) atom. The 1" C means that it is connected to
one other carbon atom; 2" C means that it connected to two other carbon atoms; 3o C
carbon is connected to three other carbon atoms; and 4o C connected to 4 other carbon
atoms. Similarly, one can also ditferentiate three types of H atoms in a given organic
molecule. They are 1o,2o, and 3o H, (but no 4o H atom). Examples of types of C and H
are shown below:
H H R R

--l\H I
('1) --l\H(2")
I
.-l\H (3) .-i\-
I I

H (r') R (2) R (l) R (4)

Naming (Nomenclature) of alkanes. The general procedure in naming of various
alkanes is as follows according to the IUPAC (lntemational Union of Pure and Applied
Chemistry) rule. This rule simply states that in a chemical name there are three parts:
prefix, parent, and suffix. The parent selects a major part of the molecule and tells how
many carbon atoms are in that part; the sutfix identifies the functional group family the
molecule belong to; and the prefix gives the locations the functional groups and other
substituents on the parent.

(1) Find the longest continuous chain (the parent chain), which may or may not be
shown in straight line, and name this chain.
(2) Number the parent chain, starting at the end closerto the branch (substituent) so that
substituent has a low number. lf there were more than one sustituent in a given
compound, number scheme of the parent chain would be such that the sum of the
number of various substituents has a low number.
(3) ldentify the branch (substituent) and its position.

20
(4) Attach the number and the name of the branch to the name of the parent.

Use hyphen to separate the different prefixes, use commas to separate numbers. lf two
or more different substituents are present, cite them in alphabetical order. lf two or more
identical substituents are present, use one of the multiplier prefixes di-, tri-, tetra-, and so
forth. Don't use these prefixes for alphabetizing purposes, however. lf there are two
substituents attached to the same carbon, give them both the same number. There must
be as many numbers in the name as there are substituents. Here are the following two
examples for the naming of organic compounds according to the IUPAC rule.

I CH. 7 CH"
t"
I
t"
I
zCHc 6CH"
t-
l4
l-
l+
H3C-CHCH-CH2CH3 NOT H3C-CHCH-CH2CH3
"
3l sl
I I
cH2cH2cH3 cH2cH2cHs
567 321
4-ethyl-3 -methylheptane
(3+4:11 (4+5:9)

t2
cH3-cHz QH3 CH2CH3 cH3-cH'
lllNor
cH3-cHcH2cH2cH-cHcH2cH3 cH3-cHcH2cH2cH-
Irs fHzcus
cHCH2CH3
76 5 4 321 34 5 6 78 9
3-ethyl- ,Tdimethylnonane
(3+4+7:14) (7+6+3:16)

Nomenclature is the vocabulary of chemistry, and allows communicating effectively with

chemical information. It involves not only to determine the chemical name for an organic
compound but also to write the chemical structure from a given name of an organic
compound. Without nomenclature effective communication regarding chemical
information is virtually impossible. Here are the two examples for drawing the chemical
structures of two organic compounds.

2t
(a) 2,2-dimethYlPentane

H
I cH3c(cH3)2cH2cl12crl3
H-l-n Condensed structure
HlnHhl
,-l-l-!-l-l-,
IIIII M I

I I
H

Kekule structure Line structure (or Skeletal structure)

(b) 3-ethyl-3-methYlnonane
H

I
H-C-H
I
H-c-H
HIHH
TTTTI
'-i-i-i-i-i I-I-I-I--
IIII
Kekule structure

H-c-H
I
H

cH3(cH2)sc (cH3xc2Hs)cH2cH3

Condensed structure

Line structure (or Skeletal structurQ

22
Cycloalkanes. They are another class of hydrocarbons having a general formula CnHzn.
They differ from straight-chain alkanes in the sense that they form cyclic structures of
spt-C atoms. Cyclopentane, cyclohexane, cyclooctane are several examples of them.

Naming of three Cycloalkanes:

T'""'

Q c(cH3)3

1,4-di -tert-butylcyclohexane
1 -ethyl-2-i sobutylcyclopentane

NOT

2 - e,thyl-7,4di m ethylcycl oheptane (1+2+6:9)

(l+2+4:7)

The chemical structure of fians-1-isopropyl-3-methylcyclooctane is as follows:

H

..otN

or

Cis-trans isomer. lt is another kind of isomer that arises in cycloalkanes because of the
greatly reduced rotation of C-C bond in this class of organic compounds, which is in
iontrast to the free rotation of C-C bond in alkanes. Monosubstituted cycloalkanes have
no isomers, but disubstituted cycloalkanes give rise to cis-isomer and trans-isomer. The

23
cis-isomer has both the substituents on the same side of the ring; the trans-isomer has
the substituents on opposite sides of the ring (shown below). Cis-trans isomers are just
one type of stereoisomers-isomers have the same connection between atoms but ditfer
in their 3-dimensional arrangements. Other stereoisomers will be discussed in
appropriate chapters.

ci s -1,2- di*hylcyclohexane tr ans - 1,2 -di ethyl cycl ohexane

Locate and identify the functional groups in the following molecule:

alcohol

CftCH2CH2
I

aromdic hydrocarbon (arene) afirne

24
 Ghapter 4 Stereochemistry of Alkanes and Cycloalkanes

Stereochemistry is the branch of chemistry concerned with three-dimensional

arrangements of atoms for molecules.

Carbon-carbon single bonds in alkanes are formed by o overlap of carbon sp3 hybrid
orbitals. Free rotation around o' bonds because of their cylindrical symmetry, and
alkanes have a large number of rapidly interconverting arrangements of atoms in space
what are called conformations. A specific conformation is called conformer
(conformational isomer). Unlike constitutional isomers that have different connection of
atoms, different conformers have identical connections of atoms and cannot usually be
isolated because they interconvert too rapidly. The interconversion of different
conformers takes little energy that is available to the molecules even at room
temperature.

Chemists represent conformational isomers in two ways: Sawhorse representations

that view the C-C bond from an oblique angle and indicate spatial orientation by showing
all the C-H bonds; and Newman projections view the C-C bond directly end-on and
represent the two carbons atoms by a circle. Lines going to the center of the circle
represent bonds attached to the front carbon, and lines going to the edge of the circle
represent bond attached to the rear carbon. The advantage of Newman projections is
that they are easy to draw and the relationships among substituents on the different
carbon atoms are easy to see.

)(T
u
S awhorse representation

r/-,.
carbon

Newman projection

Front carbon

Figure 4.1 A sawhorse representation and Newman projection of ethane.

25
 Rin-=
'-) * }tr-,,r,
Cqdo,llkcrr-t :, arlt f* {*.r*t r}lts'r?rt :-tt rt -{it}'-- 1 il
J
6gry1{q1r 6rri*. r : f;.r .r r'1-y ' 1nr.rtt'";1 \ t.}- 3 f rYr:*.trl,
'} .

Onn6l* gh-nttr " $[,*tu lk:u ** e(ryrrt.avr-r {ir{" 4r;5''-,o31in&tutl

- cl; \::rrcl nrr4kt
i{ (s *c,t*rurr,I 9t"frnr* " :frrrrr nute tre ffilrp*rrg tF: t':urr,:lu ffi'l
\x tril'l 7r",r 'l t-,.i l*:;t ' J3

:*: "*fu3tryr,* dl,qrm, 'xltarri ctrat- *c) e't:1:iil*rve tffit:r.$":t.r";ti:c;t"r$

H uul.u n el-trrr> *trlp{',)r:!e\r tt*c} r ettrc. r"-
'F't-' r\ut*ly
Ettenc<taggu€d
oonlbortiort
l**ot C1c\opr'-t^,.lt,
er
[-"t",t
?o toq,*'
4.0 hl/mol

HH \or1. (lt>*Urh*r I

4.0 kJ/mol
,A,
\€ - iiz" 4.0 kl/mol
(ti;q' -+ bd )
ttut e&'tt,* t-;ry*
b;.,x*

Etbrao-'-ocll1lced
conftrrrtto

Figue 4.2 Staggered and edipsed conformation of ethane'

T
I
lll LJltrot

.4,+t A#,4,

Figure 4.3 Aplot of potentiatenergy versus bond rotation in ethane'

26
 +
c!.

H
'!e
CtaEthc

Dihoilral anglc between methyt Sroups

"A

Gaucbe
"4,
Lcaatstable ediPeed

ir#f#;1*3,4,,i:E:i"ST,;ff :'J,E5.j'"[:["J,3"3f;,1##"^i#i;rhree
prr{eciions.
 H- HH HH HH HII. H
\,,' \,i \/ \/ \i
-zCrc,zC-.c7Cr
H- 'c,zC:.c-C- q_-H
/\
H HH
/\ HH
l\.
HH
/'..
HH
l\,H
yr'hich all substituents are
Fioure 4.S The most stable alkane confonnation is the one in
stiggerEd and the C4 bonds are anangred anti.

-(1f stable. Three kinds of strain contibute

All crcloalltanes ane not equally to the owrall.

Li"rgy;f cydoalkane. ilngle strain- tlre resistance sf a bond angle.to

*ri[66n "n irorn the nsnnal il09.5" tetrahedral bond anglg; (2) torslona!
"i "rerosion
;;t--fi;-;;,Briost or';ravir,tg nei,ghboriEp GH bond eclipsed raarertran staggered;
#'frin- the.resu[-of reiulsirc intemciion thatrises wtren tvregrrpu P b
"^Jiil,Seac
;;il til S"re qpae. Cy.do-propaie'and cyclsbutane have both angle Sfrain and
i"ffi,i"iiGin. iv&"p.ntineil! fi.pe of angle'sbainbut has a substantialtorsionalstrain
;;;-i;.,it"hree himbir of eclipslng interaciions. Both cydobutane and cydopentane
;A;; iighd-V away frorn ptanarityto relieve torsiqml stnain. The confonnations of
fi"foprof6ne, cyO6Outane and Gycloper,rtan€ apB shoyrr belovu

)<
E F n) p"ripuoa

H ll Hircrinse.a

Not quite
edivt*dfie
/"

28
 ,H
$
obsver
)ntormation' in wtricfi all bond

f, I#*flH*H**{'Ht'p$t#,ffi}
d ,*.
equator the LH[;[uo iJ=
"#axra
nn" &r"toriar pos,ion' chair
wh*l
anb
"i"*
rr. Uil- *n undergo a ring-flip'
cydoheronr= ,*-#'t],ril'iio""1iposilions'"nJ
interconrerts axal and equatorial
a
a
Movc thie a
cefton ddto
i
a
a
a
Move this
car{ron uP ![aoYl+ry
I

ff
**-*, ll*'-o',
a
a

a
!
a
I
a

posi,ons'
in clrair conformation interconverts axiar and equatorial
Figure 4.6 A ring-flip

29
Conformations of substituted cyclohexanes

Monosub stituted cycl ohexane

(r)

. I i,
llng-rttP _

,jL^)\\
.ix* P?,,,
1,3-draxral rnteractlons
(e)
o",.lg
more stabiE-) l.l L") u]]re Pat(
no 1,3-diaxial
-

Di sub stituted cycl ohexane

1,3 di axial interactions

CHs (a)

Both conformations are equally stable

tr ans-1,2-Dimethyl cycl ohexane

HcH3(e)
HcH3(e)
more stable -\ CH.1a;
no l,3-diaxial interaction

30
c i s -1,2 $imethyl cycl ohexane

9Hs (a)

CH3 (e)
CH3 (e)

Both are equally stable in which each of them has l,3diaxial interactions of one methyl gtoup.

tr an s -1,3 -Di m ethyl cycl ohexane

9Hs (a)

CHa (e)

Both are equally stable, since eaeh of them has l,3diaxial interactions of one CH3 group.

cis-I,3 -Dimethyl cyclohexane

HcH3(e)

more stable
no 1,3-diarial interactions

31
trans -7,4 -Dimethyl cycl ohexane

CH3 (a)

CH3 (a) (e)

more stable
no 1,3-diaxial interactions, since
both the methyl groups occupy
the equatorial positions

ci s- 1,4-Dimethyl cyclohexane

CHa (a)

(e) ftc
(e)

Both are equally stable, since each of them has l,3diaxial interactions of one methyl group.

ln substituted cyclohexanes, the substituents on the ring are more stable in equatorial
positions, because axial substituents cause l,3diaxial interactions. The amount of this
steric strain caused by an axial substituent depends on its bulk (small or large group).

32
 '.I
Chapter 5 An Overview of Organic Reactions

To the undergraduate students, organic chemistry is a collection of millions of organic

compounds, dozens of functional groups, and an endless number of organic reactions.
With study, it becomes clear that there are only a few fundamental concepts that unify all
of the organic reactions covered in a typical organic chemistry teXbook. When these
concepts are understood, leaming organic chemistry becomes much easier and
memorization without understanding can be minimized. Here are the following principal
types of organic reactions:

(1) Addition Reaction. As the name implies, this reaction occurs when two or more
reactants add together to give a single product.

A+B"+C
HH
,/
H
ll
-{ \
H
* HBr

tt
H-C-C-Br
HH

(2) Elimination Reaction. This reaction occurs when one reactant splits apart to give
two products. Thus, elimination reaction is reverse to the addition reaction. ln this
reaction, one gets the product that contains either double-bond carbon atoms (alkene) or
triple-bond carbon atoms (alkyne).

H H
H
I I \_
c c * HBr

I I
-Br H
/c- \
H H

(3) Substitution (or Displacement) Reaction. This reaction takes place when two
reactants exchange parts to give two new products.

AB+CD+A-C*A-O
lisht
CH4 + Cl2 CH3CI + HCI
-:+
* o,N-No2
risht
.
O Cy-"t HNo2

JJ
(4) Rearrangement Reac'tion. lt takes place when one reactant undergoes a
reorganization of bonds and atoms to give an isomeric product.
------...--..-.-_..-.*B

H3CH2C.
" '\ .H @..o HaC.
_/ H'xi \_,/
.H

,/t-"\ ,/"-"\
HHHCHS

:O:
-
@ o..
NH4-,6-C:N,
A(heat) ......
--+
il ,.
H2N-C-NH2
(urea)

(5) Oxidation Reaction. ln this reaction, the product contains either the increased
number of o>ygen atoms (other electronegative atoms) or the decreased number of
hydrogen atoms.

tol
cH3cH2oH cH3cooH tot orH{l
(6) Reduction Reaction. ln this reaction the product contains either the decreased
number of oxygen atoms (other electronegative atoms) or the increased number of
hydrogen atoms.

tnl to+
crucooH cH3cH2oH
"'rf I

(7) Hydrolysis Reaction. As the name implies, it occurs when a reactant reacts with
HzO to give the products.
!o!
il
R-C-cl *HzQ+RcooH*nct
Many organic reactions can be classified into two major groups on the basis of their
mechanisms (detailed description of a reaction): free radical reaction mechanism and
polar reaction mechanism. All chemical reactions involve bond breaking and bond
making. When two molecules come together, react and yields products, one notices that
specific bonds in the reactants are broken and specific bonds in the products are
formed. Fundamentally, there are two ways in which a covalent bond is broken in a
given reaction: homolytic cleavage (fishhook arow) and heterolytic cleavage (full-
headed anow).
n.*.e
^tft+
A4+n@+9e
34
Similarly, there are also two ways in which a covalent bond is formed: homogenic bond
making (in free radical reaction) and heterogenic bond making (in polar reaction) as
shown below:

oGtr.__...-+A-B (Radical)

n
Ao + e,g
(Polar)

-*
Free Radical Reactions. Reactions that involve symmetrical bond breaking and bond
making are called free radical reactions. A free radical (often called radical) is a neutral
species (intermediate) that contains an odd number of electrons and thus has a single,
unpaired electron in ohe of its orbitals. Although free radical reactions are not as
common as polar organic reactions, they are of significant for many commercial
products. Example of a free radical reaction:
hv
cH+ * ct, cH3cl * nct
Mechanism.

Initiation
5.7r'. light
:Cl.-l,l-Cl: -#:Cl.t.Cl:

Propagation
'*.ffif)"i: + .cH3 + n-il,

+ftC-it,

.Aa-
+ lCl' --+:Cl-Cl:
Termination 'Clt
,6,f)1cH3 +,i-r-cHs

,.r."f]1cHs + ruc-cH3 (sideproduct)

Polar Reactions. These reactions are indeed more prevalent than free radical reactions
in organic chemistry textbook. Polar reactions occur because of the attraction of positive
and negative charges on different functional groups in organic molecules. Most organic
compounds are electrically neutral; they have no net positive or negative charges.
However, certain bonds within a molecule, specifically the bonds in functional groups,
are polar. Bond polarity is a consequence of an asymmetrically electron distribution in a
bond and is due to the ditference in electronegativity of bonded atoms (Remember!
electronegative atoms are halogens, oxygen, and nitrogen--). The polarity patterns of
some common functional groups for many organic compounds are shown in Table 5.1.

35
 FunctionalGroups
Table 5.1 Polarity Pattems in some common

Functional
Functional gfoup
group Compound
Compound type stnrcture
type structure

\s+ 6-
.C: 6-
\o+
O
on CarbonYl
Alcohol -'c -
o
\/ i+ //hE-
Alkene C:C CarboxYlic acid -_C
/\ \o-
OH
Symmetrical, nonPolar
O
\o* a- t*// 6-
Alkyl halide -c-x CarboxYlic acid
chloride
-C \a-
CI
\a+ 6-
o6-
Amine -c-NHz un//
Aldehyde -C
\o+ 6- s+/ H
Ether -C-o-c-
/\ o
6+ 6- u*// 6-
Nitrile -C=N
Ester -C
\-.
Grignard JA;-iius* o
o*// 6-
reagent
Ketone
_C
\o- ,!+
C
Alkryllithium -C-Li

of all polar organic reaction is

Because unlike charges attract, the main characteristic
with electron-poor site in another molecule'
that electron-rich site-in one molecule reacts
chemists only know the terms
ln refening to the tp""i"t involved in potar reaction,
is positively charged) and
nucleophiles (nucleus-loving) (nememoer! a nucleus
Nucleophiles are elther neutral
electrophites leteciron-rovln6l in their repertoire.
ione-pair of eiectrons on them or negatively
morecures containing certain atoms n"ririg
charged on certain atoms on them' \

36
 @o-
H3C-O-H and Na :OH are two examples of nucleophiles.

Electrophiles, by contrast, are either electron-deficient around certain atoms or positively

charged on certain atoms in their molecules. BF3, H*, and partially positively charged
carbon atoms of all carbonyl compounds are such examples. ln a polar reaction, a bond
is formed when a nucleophile donates an electron pair to the electrophile. This
movement of electrons is indicated by full-headed arrow showing the direction of
electron flow from the nucleophile to the electrophile. (Never the other way around!) One
such polar reaction is shown below, and this polar reaction is a substitution reaction,
since the product is the substitution of bromide of methyl bromide with the nucleophile.

'fr'f,,\s*n.6 :o:
il
H3C-C-CH2 + H3C!Br: H3C-C-CH2-CH3 + NaBr

tt
AA
nucleophile electrophile
-)
Table 5.2 Some More Nucleophiles and Electrophiles
..o ..o
H3N:
tt tt HO,
H2O: !Br:
I r"*, nucleophiles(electron-rich)
)

@ 6+ 5-
H CH3 Some electrophiles(electron-poor)

t -Br
-[{
t }
Reaction Mechanism. The detailed description of how an organic reaction occurs is
called an organic mechanism. lt must take into account all known facts. For some
reactions, the number of known facts is considerable, and most chemists accept the
specific reaction mechanisms. The mechanisms of many other organic reactions are still
quite speculative. For molecules to undergo a chemical reaction, they first collide. Most
collisions between molecules do not result in a reaction. lnstead, the molecules simply
rebound. To undergo reaction, the colliding molecules must contain enough potential
energy for bond breakage to occur. Also, the orientation of the molecules relative to
each other is often an important factor in determining whether a reaction will occur. A
chemical reaction can be represented pictorially using a reaction energy diagram, which
follows the reaction course from reactant(s) through transition state (TS) to product(s).
The transition state is an activated complex occurring in the highest-energy point of a
reaction. The amount of energy required by reactants to reach this high point is known
as activation energy, AG+. The higher the activation energy, the slower the reaction is.
ln a single step reaction, reactants usually go through single TS to the product(s) as
shown in Figure 5.1. However, many organic reactions occur in more than one step and
involve the formation of a reaction intermediate. A reaction intermediate (Figure 5.2) is
a species that lies at an energy minimum between steps on the reaction curve and is

37
formed briefly (lifetime 10-6-10-e s) during the course of a reaction. Usually, reaction
intermediates can be detected, but not isolated from the reactions because of their short
lifetimes. Because of their short lifetimes they lead to the isolable products from the
reactions.

Reaction progress + Reaction pmgrcss+

(a) (b)

Eeaction progreas + Reaction progress+

(c) (d)

Figure 5.1 Energy diagram of a single-step reaction showing reactant (in the left hand
siJe), product (in the right hand side), TS (in the middle), and AG+.

38
 ,et
X"*o
. "-it
L!-
,,,
r\' Firet transitiou state carbocation intermeiliah ft*t'r"6 I t"l**te)

HzC=dH, +-rG-r-----T-
I

Beaction Progress -----|

Figure 5.2 Energy diagram for a two-step reaction that exhibits two transition states at
high-energy maxima and a reaction intermediate at low-energy minimum between the
two steps.

For a generalized reaction the equilibrium constant, Kuo, is defined as follows:

aA+ bB=- cC + dD

IProducts] tCl"ID]d
-r'q-
r\-^
IReactantsl 1e]"Ig]o
l'
I

Equilibrium constant

The energy change that occurs during a chemical reaction is called Gibbs free energy
change, AG. For a favorable reaction, AG, has a negative value meaning that energy is
released to the sunoundings. Such reactions are said to be exergonic. For an
unfavorable reaction, AG, has a positive value, meaning that energy is absorbed from
the sunoundings. Such reactions are said to be endergonic. The G. and AG" are
mathematically related as follows: (both measure whether a reaction is favored)

AG" = - RT ln Gq or K". = g-AG'lRT

There are two expressions for the free energy change for a reaction:

39
AGo = AHo -TAS" (Standard-State conditions)
AG = AH - TAS (Nonstandard-State conditions)

The free energy change AG is made of two terms, an enthalpy term, AH and a
temperature-dependent entropy term, TAS, where T is the temperature in Kelvins. The
enthalpy change, AH, is called the heat of reaction and is measure of the change in total
bonding energy during a reaction. lf AH has negative value, the bonds in the products
are stronger (more stable) than the bonds in the reactants, heat is released, and the
reaction is said to be exothermic. lf AH has positive value, the bonds in the products are
weaker (less stable) than the bonds in the reactants, heat is absorbed, and the reaction
is said to be endothermic. Also note here that breaking bonds absorbs energy, making
bonds releases energy. The entropy change, AS, is the change in molecular disorder
during a reaction. When is AS negative, disorder decreases; when is AS positive
disorder increases.

40
 Chapter 6 Alkenes: Structure and Reactivity

Calculation of Unsaturated lndex (A). Alkenes are hydrocarbons that contain one or
more carbon-carbon double bond(s) in their chemical structures. They are also called
unsaturated hydrocarbons because they contain fewer hydrogen atoms than alkanes, of
course, with the same number of carbon atoms. Their general molecular formula, like
cyCloalkanes, is CnHzn, but alkaneS have the general formula CnHzn*2. ln general, each
6ng or double bond in a molecule conesponds to a loss of two hydrogen atoms from the
alkine formula CnHzn*2. Knowing this relationship, it is possible to work backwards from
a molecular formula to calculate a molecule's degree of unsaturation (O){he number of
rings/double bonds/triple bonds present in a molecule. The calculated ft for a molecular
formula tells us for all of the possible chemical structures. Using several molecular
formulae and calculating A values show several chemical structures for a given
molecular formula.

Molecular formula (CroHre): A - (2x10 + 2-16)t2 = (22 -16)t2 = 612 =3

The unsaturated index for the molecular formula CroHrs is 3. lt means that in all possible
chemical structures there will be 3 double bonds or 1 double bond and 1 triple bond or 3
rings or 1 ring and 2 double bonds, or 1 ring and 1 triple bond.

Similar calculations can be performed for compounds containing elements other than
just carbon and hydrogen with a little ingenuity. Several of them are shown below:

Molecular formula (CsHaO): lgnore the number of orrygen atom(s)--' CsHe".

() = (2x5 + 2-8)12 = (12-B)12 = 412 =2

H-C=C-CH2CH2CH2OH H3C-C=C-CH2CH2OH H2C=CH-CH=CHCHzOH

jo* iln" \^o--

41
Molecular formula (CrHoBrz): Add the number of halogen atom(s) to the number of
hydrogen atoms--"C+Ha".
A- (2x4+2-8)12 = (10 -B)12=212=1
HrC=CH-CH-CH
-tl HcC-CH=CH-CH,
-f 1 '
l$y: :$y: : B..r: :Br:

A - (2xO + 2-4)12 = (14 4)12= 1Ol2 =5

H- C= C - C = C- CHz- CH: Iri - n H-C=C-C=C-CH=CH-NH2

tNHz
t-
H-C=C-C=C-C=CHz H3C-CH:CH-C=C-C=N:

\=-,
H2N-C=C-C=C-CH=CHz

ffic=ru' AA"=*,
Notice that alt of the possible chemical structures for each of the molecularformulae are
not drawn.
Naming Alkenes. lt follows a series of similar rules to those of alkanes with the suffix-
ene instead of -ane to identify the family or class. ln short, there are 3 steps: name the
parent hydrocarbon that contains the longest carbon chains including the double bond;
number the carbon atoms in the longest chain; and write the full name.

H3C-CH2*,H
,C=Gr
H3CH2CH2C'2 t H
543 2, 3 -dimethyl cyclopentene
2-ethyl-1-pente,ne

Just as R- as an alkyl group in naming the complicated alkanes, here are the following
groups in naming complicated alkenes.

,r"=l= ,r"=""-f- H2C=CH-CHz-)-

t
a

a mettrylene group a vinyl group an allyl group

42
Cis-trans isomerism. Unlike alkanes, the lack of free rotation around the carbon-carbon
double bond, many substituted alkenes shows cis-trans isomerism (for disubstituted
alkenes except those that contain two identical groups are attached to any of the double-
bond carbon atom as shown below) or E- and Z-isomerism (for trisubstituted and
tetrasubstitued alkenes for which this isomerism exists. Remember! Some trisubstituted
and tetrasubstituted alkenes also do not show E-Zform as shown below). Several
examples of this stereoisomerism are shown below.

I (No crs-trans isomer for monosubstituted alkene). lt is a monosubstituted alkene,

since one substituent (methyl) rather than hydrogen is attached to the double-bond
carbon atom.

"\_ t-u ^/*

,/\
I

ll (No cis-trans isomer for disubstituted alkene). lt is a disubstituted alkene, since two
substituents (methyl) rather than hydrogen atoms are attached to the double-bond
carbon atom that are identical.

lll(No EZ isomer). lt is a trisubstituted alkene, since three substituents (methyl) other

than hydrogen atoms are attached to the double-bond carbon atoms. ln its structure,
there is a double-bond carbon that contains identical methyl groups.
HgC. .CHs
\^_^,/
'\*,
H/
III
lV (No EZ isomer). lt is a tetrasubstituted alkene, since four substituents (methyl) other
than hydrogen atoms are attached to the double-bond carbon atoms. ln its structure,
each of the double-bond carbon contains identical methyl groups and, therefore, it does
not show E-Z isomer.

"\ _ /""
,/"-"\
HsC CHa
TV

43
Y ltrans-2-butene). lt is also a disubstituted alkene, since two substituents (methyl)
other than hydrogen atoms are attached to the double-bond carbon atoms. Note that
each of the double-bond carbon atom contains -CHs and -H. Between these groups -
CHs has a higher priority over-H on the basis of first rule of Cahn-lngold-Prelog (ClP)
Systems. Rule 1 states that the group having a higher atomic number has a higher
piiority over the other group having lower atomic number. Both groups are attached to
the individual double-bond carbon atom. ln this alkene, both the high priority groups are
located across the double bond and, therefore, it is a frans-isomer.

'\^_ ,@
@": \
H

Vl (cis-2-butene). lt is also a disubstituted alkene, since two substituents (methyl) other

than hydrogen atoms are attached to the double-bond carbon atoms. Note that each of
the double-bond carbon atom contains -CHs and -H. Between these groups -CHe has a
higher priority over -H on the basis of first rule of Cahn-lngold-Prelog (ClP) Systems as
indicated by the circle. Look at the groups that are attached to the individual double-
bond carbon atom. ln this alkene, both the high priority groups are located on the same
side of the double bond and, therefore, it is a cis-isomer.

rDA
q"-"P
,/\
HVIH
Vll (Z-3-methyl-2-hexene). lt is a trisubstituted alkene, since three substituents (2
methyl and 1 n-propyl groups) other than hydrogen atoms are attached to the double-
bond carbon atoms. ln this alkene structure, the high priority group on each of the
double-bond carbon atoms is circled. The two high priority groups are located on the
same side of the double bond (together) and, therefore, it is a Z-alkene (Zusammen-
alkene).

44
Vlll (E-3-methyl-2-hexene). lt is a trisubstituted alkene, since three substituents (2
methyl and 1 n-propyl groups) other than hydrogen atoms are attached to the double-
bond carbon atoms. ln this alkene structure, the high priority group on each of the
double-bond carbon atoms is circled. The two high priority groups are located across the
double bond (opposite) and, therefore, it is an E-alkene (Entgegen-alkene).

lX lt^?Z4El4, 5d i methyl -2,4-octa d ie ne.

'\ ./'
r\-\t
-

H3C-CHz-CHz
876

There are two additional rules in CIP systems to determine the priority of groups
attached to double-bond carbon atoms in complex alkenes:

Rule 2. lf a decision can not be made by ranking the first atoms in the substituents, look
at the second, third or fourth atoms away from the double-bond carbon atoms until the
first difference is noticed.

45
Rule 3. Multiple-bonded atoms are equivalent to the same number of single-bonded
atoms as illustrated below.
This carbon is bonded to I! O, O
H
I

\./c: o is equivalent to "\*,'o

,\
\t"\
t1- o./"
l
I
This oxygen is bonded to C, C

This carbon is bonded to C, C, C

l"
l-"-
is equivalent to rrrl\ \/-
+ C-n
c

i b\
\
This carbon is bonded to H, C, C, C

AIkene stability. Generally, alkenes follow the stability:

Tetrasubstituted > Trisubstituted> Disubstituted> Monosubstituted

*F<*\ *;-4H
')-<* N,*;,:1' R

R R/ R R R H R
\
H,/ H
t<H
This stability of alkenes can be experimentally determined by measuring the heats of
hydrogenation in presence of a Pt or Pd catalyst. For example both trcns-2-butene and
cis-2-butene undergo hydrogenation reaction (addition of H2 molecule) producing the
identical n'butane. This reaction is exothermic in each case. More energy by 2.8 kJ/mole
is released in the hydrogenation of cis-isomer than the frans-isomer because the cis-
isomer has more energy to begin with as shown in Figure 6.1.

46
 Reaction rror*uu ,-,-...............-uot-*

Figure 6.1 Reaction energy diagrams for hydrogenation of cis- and fians- 2-butene. The
cis isomer is higher in energy than the lrans isomer by about 2.8 kJ/mol and therefore
releases more energy in the reaction.

The observed stability of alkenes can be explained on the basis of two factors. One
factorwhat is known as hyperconjugation---a stabilizing interaction between the
unfilled antibonding double-bond (r) and a filled C-H o bond orbitalon a neighboring
substituent (Figure 6.2). The more substituents that are present, the more interactions

Antibonding C-C rc orbital

(unfilled)

I
.Bonding C-H o orbital
,/ (filled)

"--.

Figure 6.2 Hyperconjugation is a stabilizing interaction between an unfilled a orlcital and

a neighboring filled C-H o bond orlcital.

exist for hyperconjugation, and the more stable the alkene. The second factor is the
bond strength that is responsible for determining the stability of alkenes. A bond
between ai sp'-C and sp3-C is somewhat stronger than a bond between two sp3-C
atoms. Thus, in comparing 1-butene (monosubstituted alkene) and 2-butene
(disubstituted alkene). one can notice that the monosubstituted isomer has one sp'C-
ip3c and one sp'C-sp2C bond, while the disubstituted isomer has two sp'C-sp'C bonds.

47
More highly substituted alkenes always have a higher ratio of sp'C-sp3c bonds to sp3C-
sp3C bonds than less highly substituted alkenes and are therefore more stable.

,f 'f-'f 'f-'l
H3C-CH-CH r:,. *." I "*,f"r-"r,
2-Butene 1-Butene
(more stable) (less stable)

Electrophilic Addition of HX to Alkenes. The detailed mechanism is shown below. lt is

r-
an electrophilic addition reaction, since the first step involves the slow attack of
electron from the alkene to the electrophilic center of HBr. lt is a two-step reaction. ln
this reaction an intermediate what is known as 3" carbocation is formed. The carbocation
is a positively charged carbon atom having an empty p orbital. The second step bromide
ion (nucleophile) donates an electron pair rapidly to the positively charged carbon atom,
forming a C-Br o bond and yielding the addition product alkyl bromide. Without going
into the detailed mechanism for this reaction, one can predict the structure of alkyl halide
on the basis of Markovnikov's Rule. This rule states that, when HX reacts with an
unsymmetrically substituted alkene, the H will add to the double-bond carbon having
more H atom(s) and the X group will add to double-bond carbon having less or no H.

48
 Hec. ?H.
FCH, *Her +
Hr{
H3C-C-CH2
Ar H

Mechanism.

H3c)g6;-\t;G:
Hrc I.l8-g-,
(3o carbocation)

-
I

,-A:8.1: ?n,
H3c-c-cH2
O,,
T
H"C-C-rc. :Br:
;ri u'H
H
"
,--,- product)
(sole
(1o carbocation)

NOT formed
I
I

x I

I
I

H 'dii
lt
H3C-C-C-H
HsC H

(NOT formed)

atom. Hele is another example of electrophilic addition of HX to an cycloalkene:

,.\1
t\,./ |] + HBr =->l \-./ l-r;i,
..

Markovnikov's addition reaction of HX to an alkene is also called an regiospecific

' reaction, since only one of the two possible orientations of addition occurs in this
reaction.
Markovnikov's Rule: Rich gets richer and poor get poorer.

49
Reaction energy diagram for the electrophilic addition of HBr to an alkene is shown in
Figure 6.3. The reason for the formation of 3" carbocation over 1" carbocation is the fact
the 3'carbocation is more stable (therefore more easy to form having lower energy of
activation for its TS as shown in Figure 6.4) than 1" carbocation. The higher

Carbocation intermediata
Secoad transition etate

--T

I
CH"
I
;-f:uc'-
AGr+ CH3CCII3 Br

CH,
l-:
CH3C--CI{2 + HBr
--r
a6l"

_t__
cH"
CHgC-Br
t"
I

ctls

Reaction progress+

Figure 6.3 Reaction energy diagram for the two-step electrophilic addition of HBr to 2-
methylpronene. The first step is slower than the second step.

Primary transition state

1
AGin 'i'eltiery tlarrsition st.:,rl-e

(cHshc+ ct-

(cHsEcHcHzcl
(cHshcct

Beaclion prog?ss+
Figure 6.4 The tertiary cation intermediate forms faster than the primary cation because
it is more stable. The same factors that make the tertiary cation more stable also makes
that TS leading to it more stable.

50
stability of 3o carbocation when compared with 1o carbocation is explained on the basis
of two factors. One factor is the stabilizing interaction (hyperconjugation) of vacant p
orbital and a properly oriented nearby C-H orbital (Figure 6.5). The more alkyl groups

Figure 6.5 lnteraction of neighboring C-H orbitals with the vacant carbocation p orbital
stabilizes the carbocation and lowers its energy.

there are on the carbocation, the more interactions there are for hyperconjugation, and
the more stable the carlcocation. The second factor is known as inductive effect.

l.
RRRH
I, I, j,
./"\ */tl, ,/t\, 1'\H
3o: Three alkyl groups 2o: Three alkyl groups 1o: Three alkyl groups Methyl: No alkyl groups
donating electrons donating electrons donating electrons donating electrons

Electrons from a relatively large and polarizable alkyl group can shift toward a positively
charged carbon center than the electron from a hydrogen. Thus, the more alkyl groups
there attached to the carbocation center, the more electron density shifts towards the
this positive center and the more inductive stabilization of cation occurs. Carbocation
stability follows the order on the basis of hyperconjugation and inductive effect:

Tertiary (3') > Secondary (2") > Primary (1') > Methyl
RaC* > R2HC* > RHzC* > HsC*

Hammond Postulate. lt explains intuitively the reaction rate (how fast or slow) and
intermediate stability by looking at the energy level and structure of the transition state
(TS). The TS represent energy maximum in the energy diagram of a reaction. lt is a
high-energy activated complex that occur transiently during the course of a reaction and
immediately goes to a stable product. Although the TS is not obseryed, because it has
no finite lifetime. This postulate states that one can get an idea of the structure of the TS
by looking at the structure of nearest stable species. ln an endergonic reaction (Figure
6.6a), the energy level (thus structure) of the TS is closer to that of the product than to
that of the reactant, since the TS is energetically closer to the product. Conversely, the
TS for an exergonic reaction (Figure 6.6b) is closer energetically, and thus structurally to
the reactant than to the product.

5l
 r- f\
Transition state Traneii;ion stato

Reactant
\
\
\
Reactant
\
*"t*:
Reaetionprogregs '"'._ Beaction progres.
(a) (b)

Figure 6.6 Reaction energy diagrams for endergonic and exergonic steps. (a) ln an
endergonic step, the energy levels of TS and producf are similar. (b) ln exergonic step,
the energy level of TS and reactant are similar.

52

HAMMOND POSTULATE
1955 paper used transition-state theory
explain structure-reactiyity relationships
uf,lNG TIIB r94OS AND r95OS,
phpical organic chemists were
struggfing to explain why zub-
tle changes in the sm:cmre of
reactants affcct thc rate of
chemical reactioog and tleirproduct dis-
to
inal work by several organic chemists, in-
dudiog the late Ronald P Bell of Oxford
Universityasu,ell as tlre late.Merdith G.
Evans and thelate MidudFolanyi ofMan-
chester l)nivereiql in Eqglend But unlike
earlierworlc, the postulate allowed oryan-
fact, a similar idea had been put forward
byFlorida Srate Univers(y'sJohn E. Lef-
6er a few years eadrcr lScience, 1L7,340
(1953)1.
But the qualitative nature of
llammond'sversion-there isn't asingle
mathematical equationiohis 1955 IACS
paper-gavf it staying power, Ti.uhlar
says.
But Hammondt idea wasn't a "slam
dunk," notes M. Ftederick Hawthome,
professor of chemistry at the University
of California, Los Angeles. AltJrough it
was alreadyentrenched inphysical chem-

tibutions, Competing theories and con-
fusionreiped.
George S. Harnmond, thea ayoung as.'
sociatc profes$or of organic chemistryat
krwa Stae College, thought he ould do
better bythinking about organic reactions
in terms of theirtransition states asvell as
tlreir reactans and products. In 1955, he
suggested that transition-state theory-
rfiich had previouslybcen the domail of
physical chemists-could be used in a qual-
itativc manner to o<plain stnrcture-reec-
tivttyrelationships in avariety of organic
reactions"
Flammond laid out his postulate in a
fuarul oftbeAnerican Cbanical Sarirty pa.-
per tlret ranls among the 125 most cked
inlGl history 177,334 (I95DI "If tu,o
states, as frr example, a transition 6tate
tI
E This idea has beer used, for rx-
I ilTUITIVE Like many others, Hammond-
shown here nearly a decade after his seminal
paper was published-found his postulate to
be a useful pedagogical tool.
and an uostable interrrediate, occur con-
Sec$iveb' during a reactiOn Pr'oess {nd
havrnearlythe sarnE ererg/ cotrtent, ttreir
interconversion will involve only a small
reorganization of the molecular struc-
tures." That is, along tbe reaction coordi-
nate,spedesu,itlsimlrenergiesalso have
similar stnrctures.
Flammonds postulate built upon sem-
1/\r
ic chemists to discuss tlre outmmc
ofcomplexrvactions in terms of
the structurE oftheir transition
states,
llammond managed m identi-
frtlmc rcactions orreaction steps
in which the trartsitior. stat€ carr
be assumed to be reasonably ap
proximated by the structue ;f a-
ther the reactang inermediate, c
prodrrt. He cantionod that doing
so is onlyacteptablewLenthe two LO0K-ALIKE Hammond poslulated that
species'energies are similar. In in highty exothermic reaGtions ll€ft! the
higlrly enothermic reacrions, the lran5ition state lTsl ls structuratty simitar
transition $ate closely resembles to the reaclant {Rl, but that in highty
the nactant; in hffi endorher- 6ndoth€rmiG roactions lrightl the product
mic or*s, thc prodrrt is a beter lPl is a better model of the transition
model for the transition statc. state. He cautloncd agalnEt using the
Thc cncrgy ofa transition postulate in more thermoneutr.t
state relative to *rat ofa reaclions lcenterl.
reactant, intermediate,
or product dctermines
the position ofthe traasition istrX transiuon-state theory was uofa-
state along the reaction coordi- miliar to many organic chcmists $/hen
nate.This h turo deterrrines thc llammond published his paper. It took
selectivity of reactions that give some tirne to tate of{ Ilawthorne says,
two or more possiblc products, but it wasa't long before the llammoad
postulate became embedded in the frb-
ample, to erplei. the effects of ric of organic chemistry
subsdruents on the rate of be r- As Fhrnmond had suggpstd chemists
zilic acid rearrangements. The put it to use in explaining stnrctr.Ee-reac-
qpe ofre'arrargcmcnt prcft rrcd tivity data fo'r a wi& variery ofreactions,
by unsymmetrical beazils can be including electrophilic aromatic substitu-
predicted by using the structure tionreactions and rcactions involvinghiglr-
of thc intermedrate that forms lyreactirre intermediates such as carboni-
upotr ettackofhydroryI ioa as a um ions and carbanions.
model of the transition state. In additioq anumberof chcmists, in-
"It was simple-minded stuff, cluding Edrard R.'fhomton of the Uai-
but it had not been statd at the versity of Pennsylvania and Rudolph,L
time," Hammond dcmurs. But thc pos- Marcus of California lnsdrurc of Tech-
may be the secret to its nolog6 have me& keycontributions to er(-
*;;':*OU"O padLgtbe lh:nrnondposhJatc. -,quAN-
"Flamaond's posrulate became vide- DAYARNELL
Iy used and appreciated, not so much bc-
cause itwas revofutionarybut berxr:sc of CfEN * ekbmthg tln 125* wluru oftu
its clariry and geaeraliry" sap Donald G. Journal of tlreAmerican ChemicalSociety
Tiuhlar, a professor of chemistry at the b7 leotilring sehct€d paper fma aaoag itt
University of Mioncsota, Trin Ciries, In l2S rlott citrd. Thit pp* aur ranhd 15th

Chemical and Engineering News 2003, 81 (20), 42.

53
Any organic reaction, which undergoes a carbocation (an intermediate common to many
organic reactions) chemistry, is often associated with rearrangement reaction. This
anangement always occurs because of the transformation of initially formed less
carbocation to a more stable one (or isomerization of initially formed carbocation to the
more stable one). This transformation occurs because of either hydride shift (:-H) or alkyl
shift as shown in the following three examples.

(l) 9Hs H
?H,
-
HgC-C-C=C1 * ncr H3C-C-CHz-CHg

'i,l'Ho ct

Mechanism with ,H shift

..o
:Cl :

6'n
I
s
ntc, @ ,H
HLCI : H"C-C-C-C--H
- t,,
Ul rl
HH
(2o carbocation)

b
+
H"C H
9n' I
H3C-C-CHz-CHs H"G-C-
:Cl ,
"@ ?-cn.
H
,)
'Cl (3o carbocation)
This reanangement by hydride shift occurs because of the transformation of a 3"
carbocation from a less stable 2" carbocation.

54
(2) ?Hu ?n.
ruc-C-CH=CHz * UCI H3c-?-?H-cHg
cHs ct cH3

Mechanism with methyl shift ( ?cH. )

- ..o
:Cl :

?". ,,^.6-A.tHLCI : n.c, @ T

H"C-C-CH4CH"
-t H3C-CJCH-CHz
CH.
cHs ", (2o carbocation)
I

- +

?Fl'
H3c-c-cH-CHs .+-- ?n.
?H'
H3c-$-fH-CHs
: C-l: CHg / CHs
" e-/
, Cl , (3o carbocation)

This reanangement by methyl shift occurs, since by doing so it forms a more stable
3"carbocation from the initially formed less stable 2o carbocation.

(3)

+
Mechanism with alkyl shift.
erct

-d*
..o

flff.q:- | (3" carbocation)

-er
,.")
'q! ' (3o carbocation)
This rearrangement by alkyl shift occurs through the transformation of 3" carbocation to
a new 3o carbocation resulting in a 6-membered cyclic versus S-membered cyclic
product.

55
 Vladimir Prelog was a Professor Chemistry at the Swiss Federal lnstitute of Technology
(ETH) in Zurich and shared the 1975 Nobel Prize in Chemistry for his lifetime
achievements on the stereochemistry of antibiotics, alkaloids, enzymes, and other
naturally occuning molecules.
George A. Olah is a Professor of Chemistry at the University of Southem California and
received the 1994 Nobel Prize in Chemistry for his work on carbocations.

!*

56
 Chapter 7 Alkenes: Synthesis and Reactions

Synthesis of Alkenes. Alkenes (unsaturated hydrocarbon) are usually prepared by

elimination reactions from alkyl halides (dehydrohalogenation) in presence of strong
bases and from alcohols in presence of strong acids (dehydration). These elimination
reactions are shown below, but their mechanisms are discussed in Chapter 11.

HR
i' 'i --" (aq)
'KoH r-r/ ) R.
--'c=c'.R
R-c-c-R
II RR
)"="1 +xxtnri:
R !X:

| '?-' Hrsoa. heat R- ,R

tt R R
RR
Reactions of Alkenes. Because of the presence of n-electrons in alkenes they are very
reactive in contrast to alkanes (saturated hydrocarbons). They'undergo many
electrophilic addition reactions:
(1) Electrophilic addition of HX to alkenes leads to alkyl halides in accordance with
MarkovnikoVs rule is discussed in Chapter 6.

(2) Addition of )Q (wher€ )Q = Clz or Brz) to alkenesleads l,2dihalides (vicinal

dihalides). The product is anti addition as shown below. No syn addition product
indicates that the reaction intermediate is not the free carbocation one may think of.
lnstead, this reaction goes through a cyclic bromonium (halonium) ion intermediate.

O * ar, /cttrct (sotvent) -----+

@
HBr
tr arrs- 1,2 -dibromocycl ohexane
(no ci s- 1,2-dibromocyclohexane)
Mechanism.

a-)A0 ,n
\ry
Kr'jlrii'- *\hu,,- fl:Q.r:

57
(3) Addition of Xz and HzO (HO-X) to alkenes leads to halohydrin again according to the
MarkovnikoVs rule shown in the mechanism.

d
CH3cH=cH, * Xzl^ro ....-+ CH.-ln-cn, + Hx

Mechanism.

(2:)
a* (lo)
H"C-CH-CH"

I o r1l, ..o
l.
Hz9 I" 'X,

,H
rO: *
.t
HX + cH3-cH-CH2
-l H3C-CH-CH2
rx'
..J'8t''x'
'x'

(4) Addition of HzO in presence of HzSOr to alkenes yields alcohols.

H
@o
HSOa
+o-H

Mechanism.
o
HSO4

\-^. @o\o,H
HHSo4 -----+ rF< -+ \

HzQ
\ I -'{-r'"*,

H2SO4 + +I
,9-H

58
(5) Addition of Hzo in presence of Hzsoe to suitable alkenes
yields reananged alcohols
is associated with rearrangement reaction'
iunexpected product). This addition reaction

>.A. *
Hzo
H
@o
HSOa
r o-H
(instead of )Q, ,

Mechanism.
o o
HSOa
HSOa

(2o carbocation)
Hze

I
H2Soa+)fr }},io'
,b-H
JHSOa

-
(6) Another example of reananged alcoholfrom a suitable alkene
(unexpected product)'

@ol /
n Hsoa
>.-\
-l * nro ' *o-H (instead of Yr-r,
Mechanism.
HS04

n'Hso!#*H <- ' *

7* ..)
urroo
Hze

(3o carbocation)

t
I I
H2SOa +
,9-H @ o-H
uV
")HSO4
-
59
(7) To avoid rearranged alcohol products from some alkenes with H2O/HzSO+,
oxymercuration and demercuration reagent is the method of choice to prepare certain
alcohols.

Hzo
>/\
/
1. Hs(oRc)r,

NaOH
- \_<
2. NaBHa, ,/ OH
(Expected alcohol)

P
Hg(OAc)2 : Hg (O-C-CHe)z

Mechanism.

@ o..
Hg(OAc)2 + :OAc

T^ +
o
,OAc

\
H.
,9' \)-<To1*ft.. :OAc
,/\
HgOAc HgOAc

I
2. uaaH+ , NaoH (aq)
{
r :.O-H
+ Hg * curcooour@(uq)

(8) Addition of HzO in presence of boranes (B2H6)(also known as hydroboration

reaction) to alkenes yields with anti-Markovnikov's rule, and syn addition occurs across
the double bond meaning that -H and -OH appear on the same side in the product.
Herbert C. Brown is a Professor of Chemistry at Purdue University and shared the 1979
Nobel Prize in Chemistry for his work on organoboranes.

60
(8) Addition of HzO in presence of boranes (BzHeXalso known as hydroboration
reaction) to alkenes yields with anti-Markovnikor/s rule, and syn addition occurs across
the double bond meaning that -H and -OH appear on the same side in the product.
Herbert C. Brown is a Professor of Chemistry at Purdue University and shared the 1979
Nobel Prize in Chemistry for his work on organoboranes.

1. B2H6
H3C-CH=CH2 H3C-CH-CH2
2.H2O2, NaOH H .q-H
Mechanism.

B2H6 : 2BH3

H
I d^t
H_B-H H3C-CH-CH2 H3C-C|H-CH2
l ?n.
*-4,
---_-----------d>
Hrc-cH{cn, ,i_ _ _u+-, H B-H CH

11"6'-CH-CH"
H"C-CH,-CH"
,' -t' -H--
H 68.-
H-B-CH2-cH2cH3 <-
A
H bnricH-crt.
d
tu.c-cHfcnz

-- -b1cnrcH2cH3)2
ry-
B(CH2CH2CH3)3
H3C-C*H--CH2
Triallqylborane

61
NaOH +

(cH3cH2cH2)3B

I
(cH3cH2cH2)ru
e oG-" 4 (CH?CH?CH2)28--OCH2CH2CH3
L
+ 9Off
J
",-\

cHzcH2crl3 \I
6..
'O-O-H

I
I
I

I
Y
o
CH3CH2CH2 rB- (gCH2ClI2CHiz + B(ocH2cH2cHr): + 99,
\64_, Trialkoxyborane

l"u
B(oHh + 3 cH3cH2cHr-QH
I

I NaoH (aq)
+

NqBQ * HzO

62
(9) Addition of Hz to alkenes yields alkanes. This addition reaction is known as reduction,
since the product contains more hydrogen atoms than the reactant. This reaction takes
place on the surface of transition metal catalyst (Pt or Pd), and syn addition is observed
meaning that both the hydrogen atoms appear on the same side in the product (vide

d
infn).

H2, PlO2

CH3COOH (solvent)

syn addition

H2

Pd / c, cH3cH2oH

(10) Addition of carbene to alkenes yields cyclopropanes. A carbene, RzC:, is a neutral

species containing a divalent carbon with only six electrons in its valence shell. lt is,
therefore, highly reactive intermediate that is generated in situ with appropriate reagents
in the reaction flask. Because it is electron-deficient and behaves as an electrophile.
*Hg(OAc), and
Thus, carbene reacts with alkenes as other electrophiles such as H*,
BH:) do. The best method of preparing cyclopropane is by a reaction called Simmons-
Smith reaction. This reaction with mechanism is shown below.

Zn(Cu)

O rutr, ether (solvent)

* zntz

Mechanism.

ether
CH2l2 + Zn(Cu) + l-CH2-Zn-l _ tt ,eH2tt
carbenoid:" carbene like "

1p.",,'-

63
 ?,,._s CHC|3, NaOH (aq)

^
Mechanism.

>l ct r"F-l:
HLC-CI Na :C-Cl: * Hro * ttacl
t 'cr
9.1'

*"u{d

(11) Hydroxylation of alkenes. lt involves the addition of an -OH group to each of the
double-bond carbon atoms with OsO+. The reaction occurs with syn stereochemistry and
1,2-dialcohol or diol (also called a glycol). The reagent KMnOa also gives identical
product with somewhat lower yields because of overoxidation.

/o'
\o,
| *rrro.
I Hro
Y

f\S;
u-., -'
Ho-\-
ro'
..rod('O:
'o-
" HO

64
(12) Oxidative cleavage of alkenes by Oe (Ozonolysis).

,9f,Q..
")6, ,6-0'
X
RR

RR CH2C\2, -78oC
\ /
V"-"iX-
+ v")J"iJ-
ll

Zn , CH3COOH I

+
*\ .. ./R
+ Q:C\
'/c:Q'
RR
:O:
oC Rr.
X
RH

RR
l. 03, c12cl2,
2. a2o2@q)
-78 il

RR
I

Y
*\
,o-.:ol
-c
n-\:o-c-R
I
"l
R

65
(13) Oxidative cleavage of alkenes by KMnO+.

R o ..o R
KMnOa, Hg9 ,X, \
)":
2 ,/c:9
R "\ heat R

,\ .r* @..o
KMnO4, HsQ ,X,
,r":"\ * co,
heat
RH

(14) Oxidative cleavage of cis-1,2-diols by HlOa.

t9'

+*/\*r\
:o:
vII

t
vII
\J!---Q ,//6'
f
Q:

t
Pl-O
\
+v ll
Q:
.c il
F O: Q:

66
(15) Anti-MarkovnikoVs addition of HBr in presence of R2O2 @eroxide) to alkenes yields
alkyl halide with different regiochemistry.

H., R-O-O-R, HBr

CH3CH2CH2CH2BT
,c=cH2
H3CH2C

Mechanism.

R-6)G 2 R-e.
free radical

R-6n?G.r: #R-g-H * 'Q."

H3CH2C
";e4fiQ,ii.+ H \.
,C-QHZ
H3CH2C , ip

:,-* GQ.: -.--.4 cH3cH2cH2cH2{.r, } .

recycle

67
 Chapter 8 Alkynes: An lntroduction to Synthesis

lntroduction. Alkynes are unsaturated hydrocarbons that contain triple-bond carbon

atoms having a general formula CnHzn-2. Their carbon atoms are sp-hybridized and the
triple bond consists of one sp-sp bond and two p-p bonds. Thus, the simplest alkyne
acetylene, CzHz, is a linear molecule with a bond angle 180" between H, C, and C
atoms. The length of carbon-carbon triple bond is 1.20 A, which is shorter than C-C
single bond (1.54 A) and carbon-carlcon double bond (1.33 A). They follow the general
rule of hydrocarbon nomenclature with a suffix-yne as discussed for alkanes (-ane) and
alkenes (+ne). Compounds containing both double and triple bonds are called enyne.
Numbering of an enyne starts from the end nearer the first double or triple bond. lf an
option exists, double bonds receive lower number than triple bonds (see examples
below).

'W 53
1-Octen-7-yne

4-Ethyl-8-decen- I -yne

Synthesis of Alkynes. Alkynes are usually prepared either by double elimination

reactions of vicinal dihalides in presence of strong base or by alkylation reaction of
acetylide anion with a primary halide (a substitution reaction). These two important
reactions are shown below, but their mechanisms are discussed in Chapter 1 1.

/^\HH
\4,' I
R_C_C_R'
I 2NaNH2 , tNHg
R-C:C-R' *
+ 2NaX ,NHg
ll
XX
(b) @o
Na NH" o@
u-rr:r^-Lt
tt v-v tt H-C:C: Na i- :NHs

n-cn2-ri.r'
I

I (to halide)
*
H-c=c-cHz-n * NaBr

Reactions of Alkynes. The reactions of alkynes, like alkenes, are also dominated by
electrophilic addition reactions.

68
(1) Addition of HX, where X = Cl or Br, to alkynes yields geminal dihalides.
(Markovnikov's rule applies.)
XH
f,)-r^:ar-u R-C-C_H ____-+
HX
R_C_C_H
tt
lt
t\ V-V tt
ether (solvent) I
ether
H XH
Mechanism.
"q\'
:X:
" I H\
ol 'X, H
,^.a+A.t'fi ( ii
p-6=ag-H --> R-C-C-H -
ll
(vinyl carbocation) If
l\$6i,t
*
:X:
tt
R-C-C-H
H

+-
'X'
R-C_C-H
lt H

tt
'X'H ..o J'!@r
:X:
(geminal dihalide)

(2) Addition of Xz, where X = Cl or Br, to alkynes yieldsl ,1,2,2- tetrahalides.

XX
x2
R-C-C-R'
x2 ll
R-C:C-Rr - R_C_C_R'
CHzClz (solvent)
ll cH.2ctz ll
XXXX
Mechanism.
/'7\

: X!-X: @
:X:\ ,i,
*_.L) *, ---------------- R
/V I

-c:c-Rr\
rXr
J -+-7T?--
A t ./'4'
'Xli"
I

:X: :X:
tl
tt
-c-c-R,#
:f,: :[:

69
(3) HgSO4-Catalyzed addition of HzO to alkynes yields to ketones.

ng2*soo3; ttro
R-C-C-H R-C-CH3
H2SOa
o
Mechanism.

*-"43Hs2*sor2-
Terminal alkyne

-
nft*H
,J HSO;
sg/
rH
H2so4 + *-l- *-.L:Jtrn*aoo'-
Hg*so42-

t
,^ :o:
'I?vl^,,* L,_1,
il
R-C-CH3
{\, Tautomerizes to ketone A methyl ketone
enol
(unstable)

70
(4) Hydroboration reaction of intemal alkynes yields to ketones.

o
82H6, (tetrahydroturan; solvent)
1.
Q il
R-C-C-R
2' NaOH (aq), H2O2

Mechani sm (simPlifi ed).

'a. ,/R

R-C-C-R
BHs
*rt:"ie-c:cfR
!ltn R
p-gZc1- Hzoz
NaoH (aq)

rOt
il
R-CH2-C-R
enol

7l
 (5) Hydroboration reaction of termina! alkynes yields to aldehydes.
1. 82H6, THF fr
R-C-C-H R-CHz-C-H
2. NaOH (aq) , H2O2

Mechanism (simplifi ed).

g- *t"-""
,r" "."_":(]
R

(Anti-Markovnikov
*-:'", H
/l -..,
H
addition)

lx:h,,r,
I',"""'
:o:
II
R-CH2-c-H

72
 (6) Oxidative cleavage of alkynes with acidic KMnOa: internal
alkynes yield carbo>ylic
acids and terminal alkynes yield carbo>qrlic acids and COz.

KMn04
R-C-C_R' R-COOH * HOOC-R'
o..oa
Hs9'X', A
KMn04
R-C-c-H R-COOH * co,

(7) Addition of 2 mole.s H2 (reduction) o! alkenes in presence

of pd/C teads to alkanes,
but addition of controlled 1 mole of H2 (reduction) oi alkynes in presence
of Lindlar
catalyst yields alkenes with cis-atkenes. (The Lindlar ca[alyst is
finely divideJpapadium
metal that is precipitated onto a CaCOe support and then deactivatel
witn noiOOCHs)z
and quinoline, an aromatic amine). This deactivation is essentiat for
controlling the
reduction reaction at the alkene stage (instead of alkane).

2Hz
R-C-C_Rr R-CHr-CH2-R'
Pd/C

H2 , Lindlar catalyst
R_C-C_Rr
(deactivated catalyst)

A cis-alkene

73
I

I
(8) Another complementary method to Lindlar Catalyst for the conversion of an alkyne to
an alkene with frans-stereochemistry uses Na/NHs, CH3CH2OH. lt may also uses Li or K
metal.
Na / NH3 R
R-c-c-R '., )c-c(
EtoH R/ H

Trans-alkene
Mechanism.

*-&c-*
-->
+
o
R_C-C_R <+
. n
R-c-c--
)
\
{ru,
+6
Na-
t/
R.6 H-O-Er
"r: "\
+
..o
Eto'
@
Na

I-
lNa

*\
./R
,ZC:C\
Trans- alkene

(9) Alkyne acidity: formation of acetylide anions that can act as nucleophiles. ln contrast
to both alkanes (pKu = 60) and alkenes (pK" = 44), terminal alkynes has a pK^ = 25
suggesting they are weak acids but much more stronger acids than alkanes and
alkenes. They undergo the following acid-base reaction. The conjugate bases of terminal
alkynes (that is, acetylides anions) are more stable than either alkyl anions or vinylic
anions because their negative charge is in a hybrid orbitalwith 50% s character, allowing
the charge be closer to the nucleus.

oo o@
R-C-C-H + Na NH2 R-C-C' Na * 'NHg
(Conjugate base
of NHr: pKu:35 )
o@
R-C-C-H + KOH €+ R-C-C' K t HzO
(Conjugate base
of uro: pKu: 15.7 )

74
 Problem #1. The pKa of acetone, CH3COCH3, is 19.3. Which of the following base is
strong enough to deprotonate acetone?

(a) KOH (PKa of H2O = 15.7)

! @o
(b) rui ic-c-H (pKuof C2H2:25)
! (Q NaHCO. (pKa of HzCOs = 6.4)

\_ (d) NaOCH, (PKa of CHaOH =15.6)

!* A base that is strong enough to deprotonate acetone must be the conjugate base of an
L acid weaker than acetone. Only (b) sodium acetylide is a base strong enough to
deProtonate acetone. The acid-base reaction is shown,Tf*,
L
L ii @o ll g@
H3C-[-CH3 + Na :C:C-H + H3C-C-CH2Na + H-C-C-H
(acid) (base) (base) (acid)

75
a

Table 8.1 TypicalAcidities of organic functional groups

Name and Example* p& Coniugate Base

Hydrochloric acid, HCI -7 cl-

Sulfuric acid, H2SO4 -3 HSO4-

Sulfonic acid 0-2

,,.G$-", -7 ,,.{>$-"-
Carboxylic acid 3-5
o o
il ll
cH3-c-oH 4.74 cH3-c-o-
Arylammonium ion 4-5

G*,,
+
'NH, 4.6

+
Ammonium ion, NHo 9.3 NHr

Phenol 9-10

G'- 10

9-10
G'-
&diketone

0 o oo
lt
cH3*c -cH?-c-cH3
ll
9
il_
cH3-c-cH-c-cH3
il

Thiot 8-12
cH3cH25H 10.6 cH3cH?s^

B-ketoester 10-1 1

oo oo
cH3
illl 10.7
ll_ lr
cH3-c-cH-c-ocH?cH3
-c -cH2*c-ocH2cH3
Alkylammonium ion 70-72
+
CH3CH2NH3 70.7 cH3cH2NH2

Water, HzO 75.7 HO-

76
llame and Erample* 9Ko Conjugate Base

Alcohot 15-79

cH3cH20H 75.9 cHlcH2o-

Amide 1 5-19
o o
il il*
cH3-c-NH
cH3-c-NH2 15

Aldehyde, ketone 77-20

o
0
il
il-
cH3*C-CH2
cH3-c*cH3 19

Ester 23-25
o
0
il
24.5
_lt
cH2-c-ocH?cH3
cH3-c-0cH2cH3
Alkyne 23-25
H-C-C-H 24 H-C-C-
Ammonia, Nll3 33 fH,
Hydrogen, H2 35 H-

Alkylamine -40

c)**, 42
o*0,
Alkene
*45
H2C:CH2 44 HrC:eH
47-43

o
Aromatic hydrocarbon

G,
Atkane
43

50*50

CHo 50 eHt

77
problem #2. (Organic Synthesis) How would you synthesize each of the following
compounds? More than one step may be required.

(l) 2-, (analkyne)

@9
NaNH2

(2) CH3CH2CH2CHO (an aldehyde)

l. BzHo, THF
CH3CH2C:CH + CHsCH2CH2CHO
2. H2O2, NaOH (aq)

or
H2, Lindlar catalyst
CH3CH2CH2-G:CH CH3CH2CH2CH:CH2

1.og
2. Zn, CftCOOH

o
cH3cH2cH2cHo + ,-[-*

78
(3) cH3cH2cH2cH2cHz-c:cH
@o
Na :NH2 oo
H-C-C-H H-C-C: Na * :NHg

l.cn.cnrcH2cH2cH2-X:
it-
I

cH3-GH2)4-C:CH

Br

KoH (aq)
NBS , hv, CCla
*

2 NaNH2

o
il
(5) cH3cH2-e-cnrcn. (a ketone)
o
HgSOa, H2SOa il
cruc-ccH2cH3 CH3CH2-C-CH2CH3

+
o
ll
cH3-c-cH2cH2cH3

79
(6)

(atrans-alkene)

o9
NaNH2
: NHo

4X,

Na / NH3

(7) cH3CH2cH2coOH (a carboxylic acid)

oc
l. 03, c{2cl2, -79
CftCH2CH2CH-CH2 CH3CH2CH2COOH * HCOOH
2. H2o2@q)
or
@ -.o
KMnO4, Hg9'X,
cH3cH2cH2C:CH cH3cH2cH2cOoH * Coz

(a cls-alkene)

H2, Lindlar catalyst

80
-

(e)H
G"r="r_Q
| , *"*r,
la
t

(lo) (fromacetytene)
A
oo
H-C-C-H H-C-CrNa * :NHe

oo
Na:C:C

Lindlar catalyst

81
 (11) (from acetylene and iodomethane)

NaNHz
H-c-c-, t H-c:c?fr, + ,**,

!-
cH3-l

CH3CH:CH,
Lindlar catalyst

HBr
Hzoz

oo
H-C:C: Na
CftCH2CH2BT CH3CH2CH2C:C-H f NaBr

1. NaNH2

/. CH3CH2CH2BT

cH3cH2cH2c:ccH2cH2cH3

H2

Lindlar catalyst

82
 Chapter 9 Stereochemistry

Stereochemistry- is the branch of chemistry that deals with 3D arangement of atoms in

a molecule either small or large.

Table 9.1 Types of lsomers in Organic Compounds

ISOIytERS

STEREOISOi ETS cor{srrTuTroNAt t3ottERs

ffi3':.:i
P#-":;
::i:'1' '
:,::

CONFONMATIOilAT CONFICURATIONAL

lsomers cannot be interconverted

lsomer can be interconrrerted by
other than by breaking bonds
rotation about a sigma bond.
(whtch rarely occurs).

[,IASTEREOI'OMER5 E NAHTIOAN ERS

lsomers that have a mlrror-image

lsomer that ao not have a mirror-
relatlonshlp to each other. They have
image relationship to each other.
opposite absolute confi gurations.

cis-ttansrsoilEns OTHEN DIASTEREOISOMERS

Occasionally called geometrlc isomers.
lsomers that have more than one
Substituents may be qltached to either
stereocenter but do not have a
side of a fixed molecular frame of refe r.
mirror-image relationship.
ence, tuch as a dng or a double bond.

83
Chiral molecules and objects. A molecule or object that is not superimposable on its
minor image is said to be chiral, meaning "handed".

Figure 9.1 The minor image of a left hand is a right hand (chiral). They are not identical.
The minor im4e of a fork is identical to the fork (achiral).

An object with a plane of symmetry is achiral, and an objec{without a plane of symmetry

is chiral.

E4
The most common cause of chirality in organic molecules is the presence of a
tetrahedral sp3-hybriOized carbon atom bonded to four ditferent groups. Compounds that
contain such chirality centers (also called stereogenic centers or stereocenters)
exist as a pair of nonsuperimposable, minor-image stereoisomers called enantiomers.
Enantiomers are identical in all physical properties except for the direction in which they
rotate plane-polarized light either clockwise or counterclockwise ( when a beam of
ordinary light passes through a device called polarizer, however, only the light waves
oscillating in a single plane pass through--hence the name plane polarized light).
This plane polarized light is used to test the optica! activity of organic molecules. lt
means that those molecules that rotate the direction of plane polarized on passing
through them are said to be optically active. Usually molecules having chiralcenters in
them are optically active.
Here are the examples of achiral and chiral organic molecules.
rO:

'l
,,3a3",-{"
l-, {"
-l
,.3-!\
l-,
"?x""1?"3

Methyl oycl oh exane (achiral) "?:."u1?"

4

2-Methylcyclohexanone (chiral)

Mirror

H H
I I

ffO--*.- i,( rilii ;l'-,,.rr i-Cr---OH

I
1_i.,cl
\CH.,

(+)-l,aelic acid (-)-I-actic acid

Figure 9.2 A pair of enantiomers of lactic acids

The stereochemical configuration of a carbon atom (represented by an asterisk) can be

depicted using Fischer projections, in which horizontal lines (bonds) are understood to
come out of the plane of the paper and vertical bonds are understood to go back into the
plane of the paper. The configuration can be specified as either R (rectus) or S (sinister)
by using CIP sequence rule. This is done by assigning priorities to the four substituents
on the chiral carbon atom and then orienting the molecule so that the lowest-priority
group points directly back away from the viewer. lf a curve arow drawn in the direction
of decreasing priority (1-+2 -+ 3) for the remaining three groups is clockwise, the
chirality center has the R configuration. lf the direction is counterclockwise, the chirality
center has the S configuration.

85
(-l-lactic acid

,-..-\
1H

Stereo View trl confrguration

::H1.

\ -t.,)
\ yt"z
$tereo View S configuration

Figure 9.3 R and S configurations to lactic acids.

86
 Here are a few examples for assigning R and S configuration to the chiral carbon:

(a)

G)

(b)

G)

H_l-COOH
ilt
OH
I
: Hoogl-on
A
\t,
I
cHs \cH.
?

(c) a $n,
H1ir3H. 3l

i
'i"razY'
CN
')
Ll../ 2
(R)

llt
H

"\l/
NHz

,-l-"r.
I ,ll
H.c-l-NH,
I
CN
)

87
{
Diastereomers. Many molecules have more than one chiral center. A compound with n
number of chiral centers can have a maximum of 2n stereoisomers.

Mirror Mirror
alii' !i i
i , /' ,/j-; : i-)i'-:i i' '.'; ;)
Hri...NH, HrN- i-H H16..,lnr' urrv- i-H '(-:

i I
I I I I

u/?\oH ,ro -?-s no-?-"

AU
L. I r:i C]I1,, i rI{.. "-?-os
i:Il-,

f? od ?rf
i

T4 t#. *dr\
T1 ?
ew
fi
w,8n

trarrtiOmer6
?&
.L
2,5,its
#
2R'ss

Enantiosrers
-+?
as'3B
'l

a.

Figure 9.4 The four stereoisomers of 2-amino-3-hydrorybutanoic acid (threonine).

Since the threonine contains two chiral center, it has four stereoisomers that occur in two
pairs of enantiorners. Notice that enan$orners have opposite configurations at all chiral
centers. They are I (2R, 3R) and ll (2S, 35) are a pair of enantiomers; lll (2R, 35) ahd M
(2S, 3R) are another pair of enantiorners
The relatisnship between I and'lll, and I and lV (similarly, ll and lll, ll and lV) is called
diasteresrner. Diastereorners are stereoisomers that are not minor images of each
other. Chiral diastereomers have opposite configurations at some (one or more) ctriral
centers, but have the same configurations at others. Enantiomers, by contrast, have
opposite configurations at all chiral centers.

88
 Mirror Miror
rCtlDI{
rtlo0H
n--c-o'
rL]0OH rCOOH
*o>i-'
l
'oli-"
I
'>6-o*
I I

sol?-n ,/?-on
rf-:(xlH ',j?-ou
+COOll tCOOll "o/?-,
a{lO0H

2R,AB 2s,As 2S,g,R

rCOOH

Rotate ,
'oli-" I
1800

nol?\n
+(l00II
2,s,gR

Identical

Figure 9.5 The four stereoisomers of tartaric acid.

Because of the presence of plane of symmetry in a second pair of enantiomers, they are
identical and aciriral (optically inactive), despite the fact that it has two chiral centers. lt is
achiral, since one nak of the molecule rotates plane polarized light to the left and the
other half rotates to the right, resulting in zero degree rotation of plane polarized light.
Compounds that are achiral, yet contain chiral centers, are called meso compounds.
Thus, tartaric acid exists in three stereoisomeric forms: a pair of enantiomers and a
meso form.

A mixture of 50o/o R-enantiomer and 50% S-enantiomer is called racemic mixture that is
also optically inactive. Racemic mixtures and individual diastereomers differ in their
physical properties, such as solubility, melting and boiling points. ln contrast,
enintiomers have identical physical properties except one enantiomer rotates plane
polarized to the left and the other rotates to the right.

Many organic reaction give chiral products. lf the reactants are optically inactive, the
proOuctJare also optically inactive either meso-racemic. lf one or both of the reactants is
optically active, the product can also be optically active.

lmportance of chiral molecules. The great significance of chiral molecules

(enantiomers) lies in the fact that the majority of compounds found in nature otherwise
known as biomolecules exists as a single enantiomer. For example, all but one of the o-
aminoacids that make up most proteins, whether human or other, exist as a single
enantiomer. All naturat carbohydrates (sugars) exist as a single enantiomer. Most other
natural products including hydrocarbons (e.9, turpentine componenls) and many
alkaloids (nicotine and morphine) also exist as a single enantiomer. Some commercially
produced drugs are sold as single enantiomer, but these are more the exception than

89
a

a great challeng-e to. the organic

the rule. To prepare a single enantiomer remains either (separation technique to
chemist or an arduo*1"ri, by the method known as resorution
isolate the single enantiomer).

!-

90
a-

Chapter 10: Alkyl Hatides

1. lmportance of alkyl halides.

FBr
tl
F--{-c-H
F
I
H

tt
I
H-C_Br
J>:<: FCt I
ct H
I

Trichloroethylene Halothane Di chlorodifluoromethane Bromomethane

(a solvent) (an inhaled anesthetic) (a refrigerant) (tumigant)

2. Naming of alkyl halides.

CHr Br
l"l Br

a
cH3cHcH2cH2CHCH3 Bromocyclohexane
6 5 4 3 2l (Cyclohexyl bromide)
2 -Bromo-5 -methylhexane

3. Classification of organic halides.

,i' ,i,I
I
cH3cH2-X: cH3-cH-cH3 I
H3C-C-CH3
I
10 20 cHs
aO
5 Vinyl halide

d
-t X: \.
""\^-^r'
\.rr-ri,
-vv

ar{
Allyl halide Aromatic halide Benzyl halide

halides. The carbon-halosen in alkyt hatide results from the overtap

1; lt:::lf ^"jflfyJ
oI a carbon sp" hybrid orbitalwith a halogen sp3 hybrid orbital. Thus, alkyl halide carbon
atom has an approximate tetrahedralgeometry, with H-c-x bond angle,
n"rr" iog ".
Since halogens are more electronegative thancarbon, the C-X bond
is, therefore polar,
with the carbon atom bearing a slight positive charge (6-) and the hatogen
a slight

91
negative charge (6-). This polarity results in a substantial dipole moment for all
halomethanes, and implies that the alkyl halides C-X carbon atom should behave as an
electrophile in many polar reactions.
-o
,X:
ectroPhil i c site
\Y\ ! *---El

5. Preparation of alkyl halides.

(1) From alkenes and alkynes.

HBr

H2O2, HBr

Br2lCltr2Cl2
+

BrH
R-C-C-H
2 HBr tt
R-C-C-H
tt
BrH
Br
R-C-C-H
2 Br2lCl-l2Gl2 II
R-C-C-H
Br

tt
Br Br

92
 (2) From alkanes by free radical substitution reaction (fhis mechanism is given in
Chapter 5).

CH" CH"
t"
H3C-CH-61'1t
Cl2, hv t" l-
CHa

Hgc-g-cru + H3C-cH-CH2CI
I
u ct

. 65% 3s%

CH" CH"
?" Br2, hv t" l"
H3C-CH-gg. -l
H"C-C-CH. + H3C-CH-CH2Br
Br
> 99Yo <lYo

(3) Allylic and Benzylic bromination by NBS (N-bromosuccinimide)

o
c,ltrylre -\
I N-Br
.t
Yo
o +yb*.yl'.
hv , CCla (solvent)

cH2cH2cH3 \_

6
cH-cH2cH3
NBS, CCIA

ry

93
Mechanism.
16r zs.l..x-
:o:

h' -+
+*,
:O: :O:
+ 'iir, cyr*rrrt* c, !rr*tx-

,f,tnr'
\cH-cH,cH" cH-cH2cH3

O
Recycle

+ H-ri-r,

-
dn-cnrcn. HC-CH2CH3

r^- 0+
I

\2

94
(4) From alcohols by using HCl, SOC|2, and PBr3. These mechanisms are discussed in
Chapter 11.

HCI (gas)
HzQ
oC
ether, 0

soct2 * soz + Hcr

e (gridine)

PBrs

6. Reactions of alkyl halides including other organic halides.

(1) Formation of organo-magnesium halides (Grignard Reagents).

Mg, ether t f
R-x: R-Mg-X
heat

Where, X: Cl, Br, I and R: 1o, 2o,3o,vinyl, aryl, or benzyl group

Grignard reagent undergoes acid+ase reaction as shown below:

tJHzo
R-uts-* *R-H*Mgx(oH)

95
 (2) Diorgano-copper Reagents (Gilman Reagents).
+
2Li 6 6
* r-ix

Where, R: 1o, 2o,3o, vinyl, aryl or benzyl group

:
dd Cul (ether)
2 R-Li

-
+
\_--
r .-Jl-* i,P
Gilman reagents undergo organometallic coupling reactions with various organic halides
as shown below:
(a) nrcut-i ar- p,-jl, ether
! - R-R' * Rcu * t_ix

n-C6H13r /H
(b) + (CH3CH2CH2CH2)2CuLi

H)c:cl\i' I
I

v
n-C6H13. ,H
)":"( +Lir *cn.cnrcH2cH2cu
H CH2CH2CH2CHS

tt*
(c) (cH3cH2cH2cH2)2cuLi
ef
I

6 cH2cH2cH2cH3

* tiar + cH3cHzcH2cH2cu

96
Problem #1. How would you prepare n-octane from n-butyl bromide by using Gitmann
reagent?

CH3CH2CH2CH2-Br :
2Li r*
cH3cH2cH2CH2-Li * Lier

6 o
f cut(ether)
vvr \err rvr ''r
cH3cH2cHrcur-ii > cH.cHrcH2cH2-cu-cH2cH2cHrcH, r-io
[ ]
* r-ir

Ir@
I
cnrcnrcn2cH2-cu-cH2cH2cH2cH3
J
ti * cH3cHzcH rc+r-11,
I

I
I

*
cH3-(cHz)o-CHs f CH.CHrCH2CH2Cu f liAr

Problem #2. How would you prepare the following compound?

from

Mg, ether

B..r

SOBr2

e
Dzo

-il-n
U +
D
MgB(oD)

97
-

Problem #3. How would you prepare the 3-methylcyclohexene from cyclohexene?

from

NBS, CCI4 2Li

+
* Liar
hv b
Li

I
",,
| ",1t".
Y
o

H3C-Br' or",D o

or

NBS, CCIA (CH3)2CuLi

* cHrcu * Liar
hv
cHs

Problem #4. Complete the following two reactions. Also name what type of reactions
they are.

+
bo @o
CH3CH2MgBT * n-c-C-R CH3CH3 * ArMg:C-C-R
(Acid-base reaction)

+
arb @o..
CH3CH2MgBT * ,NHs CHaCHs + BrMg!NH2
(Acid-base reaction)

Victor Grignard was Professor of Chemistry at Nancy and at Lyon and shared the 1912
Nobel Prize in Chemistry for organomagnesium compounds and their reactions.

98
! KarlZeigler was a Director of the Kaiser Wilhelm Institute for Coal Research at
Mtilheim-an-der-Ruhr, Germany and shared the 1963 Nobel Prize in Chemistry for his
work on polymerization
_

\_*

99
..

Chapter 11 Reactions of Atkyl Halides: Nucleophilic Substitutions and

Eliminations

The carbon-halogen bond in alkyl halides is polar and that the carbon atom is electron-
poor. Thus, alkyl halides are electrophiles at the carbon centers by definition; much of
their chemistry involves polar reactions with nucleophiles and bases.
_
.*
..1.--
--7\
a
Electrophilic carbon atom

! Alkyl halides undergo two important reactions with nucleophiles/bases. Either they
s undergo substitution reaction of the X grouo by the nucleophile (Nu:-), or they undergo
elimination of HX to yield an alkene'

Nu\ Y

Erimination + * Nu-H + xP
.p"6 )":(
These two reactions are the most widely occuning and versatile reactions in organic
chemistry.

Nucleophilic Substitution reactions of alkyl halides are of two types: S*'(S stands for
"substitution," N stands for "nucleophilic," and 2 stands for "bimoleculaf') and Sr.r' (S
. stands for "substitution," N stands for "nucleophilic," and 1 stands for "unimolecula/')
reactions.

Facts about Sr,r2: This reaction occurs with inversion of stereochemistry at the carbon
center (Walden inversion of-configuration). That is, when one starts with R configuration
at the chiral center, after Sr.r2 reaction occuning at this center the produc't is S
configuration.

It shows second-order kinetics meaning the rate (fast or slow) of this reaction depends
on the concentration of alkyl halide and the concentration of nucleophile. Doubling the

Rate=kx[RX]x[Nu:-]

100
concentration of alkyl halide doubles the rate of this reaction. Similarly, doubling
the concentration of nucleophile also doubles the rate of this reaction.

Mechanism for SH2 reaction. The nucleophile -OH uses its lone-pair of electrons to
attack the alkyl halide carbon 180" away from the departing halogen. This leads to a TS
with a partially formed C-OH bond and a partially broken C-Br bond. The
stereochemistry at carbon is inverted as the C-OH bond forms fully and the bromide ion
departs with the electron pair from the initially C-Br bond in the reactant.

,ot\jih, HO
t ------'1C,,"*r
I
t
------ Br
cH2cH3 cH2cH3

(S)-2-Bromobutane Transition state

,cH'
ro-i(* + B."o
cH2cH3

(R)-2-Butanol

Figure 1 1. 1 shows how the rate of a chemical reaction depends on AGt, the energy
difference between reactant (ground state) and transition state: (a) a higher reactant
energy level corresponds to a faster reaction, and (b) a higher transition state energy
level corresponds to a slower reaction.

The rate of SN2 reaction depends on 5 factors: nature of alkyt halides/tosylates,

nucleophiles, leaving groups, solvents, and temperature.

101
The relative reactivities of Sx2 reaction for different substrates are indicated below:

oo
R-Br * Ct- R-Ct * Ar

CH. CH"
H3C-f-Br
-->
HOC-C-CH'_Br
?u,
H"C-C-Br H"C-C-Br
H
I
H
I
H-C-Br
I

cHs cHe HH H

Tertiary Neopentyl Secondary Primary Methyl

Relative
reactivity <1 1 500 40,000 2,000,000

Less More
reactive reactive

Simply, Su2 reactions can occur only at relatively unhindered sites, and are usually
usefulwith methyl halides, primary halides and secondary halides including allylic and
benzylic halides. ln the relative reactivity scale, note that the reactivity of 3"
substrates (halides or tosylates) is less than 1 indicating that they never undergo
Sx2 reaction because the nucleophile cannot approach the sterically hindered,
carbon atom (the one to which leaving group is attached) to form the TS, thus no
reaction (Steric effect).

Electronic effect also plays a role in Sru2 reaction, as high reactivity of allylic and
benzylic halides show when compared with m-ethyl halides. At the TS for lhe Sx2 reaction
the cirbon being substituted (to begin with sp3) is transformed into an sp'hybridized
carbon, and uses its p orbital to bond with the entering nucleophile and leaving group. ln
the allylic and benzylic halides, this p orbital can be conjugated with the rest of the n
electronic system, explaining the greater stability of these transition states and thus the
higher reaction rates (shown below):

Vinylic and aryl halides are not reactive to Sx2 reactions because the incoming
nucleophile would have to approach in the plane of carbon-carbon double to carry out a
back-side displacement.

102
a

R.- f., S-C )+

*r7,1* )( No reastion Noreasrion
Arylhariib
Nrr:-
Vinylic haltdo
Nature of nucleophiles. The nature of the attacking nucleophiles is an important
variable that has a major effect on the Sx2 reaction. Any species, either neutral or
negatively charged, can act as a nucleophile as long as it has a lone pair of electrons
(that is, Lewis base). lf the nucleophile is negatively charged, the product is neutral; if
the nucleophile is neutral, the product is positively charged. The relative order of
reactivity of various nucleophiles are shown below:

Or..-,..O
Nui * R-i, Nu-R + ,XI
--=----+
: Nu' * n-i: =# N8-n + 'iP ;
HaC-Br * *rP H3C-Nu + er"
OOoOOOo
: Hzo cH3co2
Nu NHs cl oH CH3o I cN HS
_ Relative 1 500 700 1,000 16,000 25,000 100,000 125,000 125,000
reactivity

reactlve
t Nrrcleonhilic reactivitv
'- -) ':1"
reactive

103
Table 11.1 Several Sr,r2 reactions of bromomethane with nucleophiles: Nu:- + CHsBr ->
NuCH, + Br-

Nucleophile Product

Formula Name Formula Name

..o
cH3s: Methanethiolate CH3SCH3 Dimethyl sulfide
..o
H9' Hydrosulfide HSCH3 Methanethiol
o
N=C! Cyanide N=CCHg Acetonitrile
1r1=11=1,,1P Azide N3CH3 Azidomethane
..o
Iodide ICH3 Iodomethane

cH3oY Methoxide CH3OCH3 Dimethyl ether

..o
HO: Hydroxide HOCH3 Methanol
.."
,c.j, Chloride CICH3 Chloromethane
@o
H3N: Ammonia H3NCH3BT Methylammoniumbromide

cH3co2P Acetate CH3CO2CH3 Methyl acetate

@o
(CH3)3N I Trimethylamine (CH3)3NCH3Br Tetramethylammonium bromide
o
ll: Hydride CHa Methane

Some salient features for nucleophiles:

(a) Nucleophilicity roughly parallels basicity. Since "nucleophilicity" measures the affinity
of a Lewis base for a carbon atom in Sx2 reaction, and "basicity" measures the affinity of
a base for a proton in acid-base reaction, thus there is a correlation between the two
kinds of behavior.
(b) Nucleophilicity usually increases going down a column in the periodic table. lt also
changes with the nature of solvent.
For example, l- > Br- > Cl- > F- in polar protic solvents, but reverses in polar aprotic
solvent as follows: F- > Cl- > Br- > l-.

(c) Negatively charged nucleophiles are usually more reactive than neutral ones.
Table 11.2 Correlation of basicity and nucleophilicity

o OO
Nucleophile cH30 HO cH3co2 HzO

Rate of Sp2 reaction with CH3Br 25 16 0.5 0.001

pll of conjugate acid 15.5 15.7 4.7 -1.7

104
The Leaving Groups. They are an important variable for the Sn2 reaction. The order of
reactivity of various leaving groups is shown below:

oooooooo
. OH, NHr,
9L F Cl Br I TosO

Relative
reactivity <<l | 200 10,000 30,000 60,000

r ^.. Mole
. I
reactlve
Leavine group reactivir-) reactlve

Remember! R-F, R-OH, R-OR', and R-NHz are not good substrates for SHz reaction,
since, like halides and tosylates, fluoride, hydroxide, alkoxide and amide ions are not
good leaving groups at all.

Alcohols contain -OH group that is not a leaving group at all, but their conversion to alkyl
tosylates, by the following reaction sometimes called tosylation reaction, which contain
tosylate group. This group is much better leaving group even better than iodides.

105
 :o:

o
:o! ll
R-O-H S
il
o
O (n-Qr' ) +

oft'r't
H

,OP

cH3+ --p, jS"r.

k1 .. a.
rOr rO: )
-ll n /F"r' .<-
n-9-frn R-o
V,E,
il
-
+
n:$-/-
"+

Qn,, H
a
I
H

Nature of Solvents: There are two types of solvents: (polar protic solvents those
contain -OH and -NH- groups and polar aprotic solvents those lack in -OH and -NH-
g5ncLms. Protic solvent means that solvent that has polar hydrogen in its structure and
aprotic means that solvent that has no polar hydrogen in its structure.
a
a
a
a
a
o
Table 11.3 Dielectric constants (polarization) of some common organic solvents

Name Dielectric Constants Name Dielectric Constants

Aprotic solvents Protic solvents

Hexane 1.9 Acetic acid 6.2

Benzene 2.3 Ethanol 24.3
Diethyl ether 4.3 Methanol 33.6
Chloroform 4.8 Formic acid 58.0
Hexamethyl phosphorami de 30 Water 80.4
(HMPA)
Acetonitrile 37.5
Dimethyl formamide (DI\G) 38
Dimethyl Sulfoxide (DMSO) 48

Protic solvents, such as alcohols, slow down reactions by clustering around the
nucleophile, a process called solvation. Solvent molecules form hydrogen bonds with the
nucleophile, orienting themselves into a "'cage" around it and thereby lowering its
reactivity.

OR
I
H
l
I

l^
Ro-H----xi----H-OR Asolvatedanion
I
I (reduced nucleophilicity due to enhanced
t
H ground-state stability)
I
OR

ln contrast to protic solvents, aprotic solvents increase the rates of Sn2 reactions by
increasing the ground-state energy of the nucleophile. These solvents dissolve many
salts (nucleophiles) because of their high polarity, but they tend to solvate metal cations
rather than nucleophilic anions. As a result, the bare unsolvated anions (opposed to
solvated anions in protic solvents) have a greater nucleophilicity, and reactions take
place at conespondingly faster rates. The relative rate of Sn2 reaction in various solvents
is shown below:

107
--

+ Nu:
H3C-Br H3C-Nu + er"

:
ooooooo
Nu HzO cH3co2 NHa Cl oH cH3O I CN HS
Relative I 500 700 1,000 16,000 25,000 100,000 125,000 125,000
reactivity
Llor :vlore
.. I Nucleonhilicreactivit=v .)\ rYr\
reacttve reactive

Unhindered

Reactinnp?osxess .* Rea*tir;n progre$F

(a) {b)

!'olxr apxrlic

lleaction p1'ogress

{c) (d)

Figure 1 1.2 Reaction energy diagrams showing the effects of (a) substrate, (b)
nucleophile, (c) leaving group, and (d) solvent oD Sp2 reaction. Note here trraisubstrate
and leaving group affect primarily in the TS, nucleophile and solvent affect primarily in
the ground state of the reactant.

Facts about Sxr reaction. This reaction occurs with racemization (that is, when one
starts with R configuration at the chiral center, after Sp1 reaction occurring at this center
the products are 50% R and S0% S).

9H, H26,
' HrC- CH"
cr-ii:?:T..
bttrcHrcn2cHcH3 ?r, Ethanol
- n,? n,cH,c-foH *oH-c--cH2cH3
?H.
H3cHcH2c:H rdurc cH2cH2cH2CHCH3
(R) -6 - Chlo ro -2,6 - dimethylo ct ane 40%s 60%R
(inversion) (retention)

108
 '(
JF{'ra-"-r-*

.*{ e{,.*::f€. }*
r,,',,,,,,,.'',,'
I

50&bwnluof Plrry,rchiral qa:bqtto 50*Eaall@ol

coDigundo inr.6.dirt mtr8[nti@

Figure 1'1.3 Stereochemistry of Srr reaction.

It shows first-order kinetics, meaning that the rate of this reaction depends only on the
concentration of atkyl halide. The concentration or strength of the nucleophile has no
effect on the reaction rate.
Rate=kx[RX]
Itllechanism for Srt reac{ion. Spontaneous dissociation of the alkyl bromide occurs in a
slow, rate-limiting (or rate-deternining) step to generate a carbocation intermediate and
bromide ion. The carbocation intermediate reacts with water as a nucleophile in a fast
step to yield protonated alcohol product. Loss of a proton from the protonated alcohol
intermediate then gives the neutral alcohol produc{.

CH" CH"

-I IA lr",i9 ?" ,r*

Hzg
HzC-CLX: +H3C
?\-HgC- ?-"a
cHs cHs \ Cr. H

Hzg

CHo

-l
t"- *rx
H2C-C_OH
GHg

109
,

RNU +:x-
Reactioa progres6---+

Figure 11.4 A reaction energy diagram for an SNr reaction showing TS, intermediate,
and product.

Factors affecting the rate of Srl reaction:

The Substrate. According to Hammond postulate, any factor that stabilizes a high-
energy intermediate should also stabilize the TS leading to an intermediate. Since the
rate-limiting step in Sr1 reaction is the spontaneous disiociation of the substrate to yield
a carbocation intermediate, one would expect the reaction to be favored whenever a
stabilized carbocation intermediate is formed. ln other words, the more stable the
carbocation intermediate, the faster the Sr.rI reaction. The stability order of carbocation is
shown below:

@ @ PH.( Fn.
cHs ( cH3cH2 < cH3gH cHrco
cHs

This stability order of carbocations is exactly the same as the order of Sr,r' reactivity for
alkyl halides and tosylates.

The Leaving Group. An identical reactivity order, like the Sn2reaction, is found for the
Sx1 reaction because the teaving group is directly involved in the rate-limiting step. Thus,
one can find Snl reactivity to be:

ooo o
Hzo a/ TosO
L;ss }iore
reactlve reactive

The Nucleophile. The nature of the attacking nucleophile plays a major role in Sn2
reaction. ln contrast, the Sr' reaction, by its different nature, occurs through a rate-
limiting step in which the added nucleophile has no kinetic role. The nucleophile does

110
not enter into the reaction until after rate-limiting dissociation has occuned and thus
cannot affect the reaction rate.

The Solvent. The Hammond postulate states that any factor stabilizing the intermediate
carbocation should increase the rate of Sr.r1 reaction. Solvation of the carbocation-the
interaction of the positively charged ion with polar protic solvents-has just such an effect.
Protic solvent molecules orient around the carbocation so that the electron-rich ends of
the solvent dipoles face the positive charge (Figure 1 1.5) thereby stabilizing the
carbocatioo. Sr.rl reactions takes place much more faster in polar protic solvents than in
nonpolar solvents.

H ';oi" H
I I
:o..\H
,'9t
H-(i, *'iL :o
H

I I
H H
joiH
H

Figure 1 1.5 Solvation of a carbocation intermediate by protic solvent, water.

CH"
t-1"
CH"
H3C-C-CI * nOn H3C-C-OR * nCt
cHs cHs

Ethanol 40 YoWater / 6OYo Ethanol 80 % Water I 20 Yo Ethanol Water

Relative -
I 100 14,000 100,000
reactrvrty
kss
reactive ' .Uff "

Figure 11.6 The effect of solvent on the Srr reaction.

111
Comparison of SNr and Su2 reactions:

Features S*' Sr'

Rate Second-order First-order

Stereochemistry lnversion Racemization

Mechanism Single-step involves the TS only Two-step involving carbocation

Reanangement No Yes

'substrates Benzyl> allyl > methyl > 1o > 2" halides Benzyl > allyl > 3" > 2" halides

Nucleophiles strength Modest to Strong lrrelevant (at least very weak)

Nucleophile concentration Affects rate No effect on rate

Leaving groups TsO- > l- > Bt- > Cl- TsO->l->gr->Cf

Solvent Polar aprotic (DMSO, acetone) Polar protic (alcohols, formic acid)

*3" halides never undergo SN2 reaction and 1" halides never undergo Snl reaction.

1o,2o and 3o alkyl halides are easily distinguished experimentally-in simple qualitative
tests that depend on their different tendencies toward Sr,r1 and S*'. An unknown alkyl
halides is reacted separately with two solutions: (a) Nal in CHsCOCHg(iodide is a strong
nucleophile that displaces bromide and chloride ion from the conesponding halides in an
Sru2 reaction in a polar aprotic solvent); and (b) AgNO3 in ethanol (Ag* will react with a
halide ion formed by dissociation of an alkyl halide into a carbocation and a halide ion in
a Sr,rl in polar protiisolvent). lf the unknown halide reacts quickly with Nal, lt is probably
a primary halide (NaBr or NaCl precipitates, indicating Sp2 reaction) and will not react
with AgNOs solution. lf the halide reacts quickly with AgNO3, it is probably a tertiary
halide (AgX precipitates, indicating Sru1 reaction) and will not react with the Nal solution.
lf the reaction is sluggish at room temperature with both the reagents, (that is, occurs on
heating), the alkyl halide is probably a secondary halide.

nger*# AgNQ
E{t
n
L

il;tr*.
-/\
Nar
acetone
I

t12
a

Elimination Reactions of Alkyl Halides. Since all nucleophiles are bases and all bases
are nucleophiles, substitution reactions (Sp2 and Sp{) compete with elimination reactions
as shown below:

,LJ,,
substitution
.-rr,,. +oH
0
,x.*
HOH
Br
o

Elimination

+""
H,
o
* uzo *sr

ln the elimination reaction of HX from an asymmetrical alkyl halide, the more substituted
alkene is the major product (Zaitsev's Rule).

Elimination reactions are also of two types: E2 (elimination, bimolecular) and El

(elimination, unimolecular)

Facts about E2 reaction. lts rate depends on both the concentration of alkyl halide and
the concentration of base.

Rate=kx[RX]x[base]
E2 reactions always occur with anti periplanar geometry, meaning that all four reacting
atoms the hydrogen (also known as B-hydrogen), the two carbon atoms, and the leaving
group lie in the same plane. The anti means that the H and the X are on the opposite
sides of the molecule. This geometry is energetically favored because it allows the
substituents on the two carbon atoms to adopt a staggered conformation, where as syn
geometry the substituents on carbon atoms be eclipsed. Anti periplanar geometry for this
reaction has specific stereochemical consequences (E-alkene vs Z-alkene) that provide
for strong evidence for the proposed mechanism.

Mechanism lor E2 reaction. Base (B: ) attacks a neighboring hydrogen and begins to
remove the H at the same time as the alkene double bond starts to form and the X group
starts to leave. Neutral alkene is produced when the C-H bond is fully broken and the X
group has departed with the C-X electron pair.
t,)
d
jl- *
B-. -H
'-erlR R
R/r,.
'""6:6'\'."$ * @
-Y? \^---.)* o
v g-H * rX
nV
-.u
----+ R( \*
-
'...
R ^u
Transition state

113
 ,:,rrli*'
' ;) :':

Anti peripfanar reactant Anti traasition Btate Alkeue produat

Figure 11.7 The TS for the E2 reaction. Overlap of the developing p orbitals in the TS
requires anti periplanar geometry of the alkyl halide.

One can think of E2 reaction with anti periplanar geometry as being similar to Sp2
reaction with 180' geometry as shown below. ln an Sn2 reaction, an electron pair frcm
the incoming nucleophile pushes out the leaving group on the opposite side of the
molecule (back-side attack). ln an E2 reaction, an electron pair from a neighboring C-H
bond pushes out the leaving group on the opposite side of the molecule (anti periplanar).

N"@,@+4 c.s

SN2 r€action ED reaction

{back-side attaek) (anti periplanar)

714
 Trans diaxial
HCI
n Ca---e/ \
:"3- H.cG--i
,,1$ffi'""* \-ilyr""'lr *,-#ffi \-{ -cH(CILL

Neomentfurl chloride &Menthene

H cH(cHs)2
_ Hrcl\-1 \ -/ H.ca-
Hsc CI
l=i'cH(cHs)2 X \==^UcH(cHs)2
tarL-diequqtorial . B'tleutlieue

Menthyl chloride

Jf*,*-oi, lln'w-o,n

F
Trans diavinl qH(cIIs)z cH(cHs)2
t,
',-

l# Fast r
l-+-l
, ' t-I;* -ocuscrtu,-
ethanol
cHa Ldf CH,

Figure 11.8 Dehydrochlorination of menthyl and neomenthyl ctrlorides showing the

importance of anti periplanar geometry.

Another piece of evidence for the E2 reaction is the deuterium isotope effect as shown
below:

Faster reaction H
I Base
G-CH2Br
H
G"H:cH2
I -Bromo-2-phenylethane

Slower reaction
,n? Base
\ fc-cuzBr G"D-cHz
-D
-Br omu2,Zdi deuteri o-2-phenyl ethane

This result tells that the GH (C-D) bond is broken in the rate-limiting step, which is
consistent with the mechanisrn of the E2 reaction as a one-step process. lf it were
otherwise, one could not measure a rate difference between these two reactions.

Facts about El reac'tion. lts rate depends only on the concentration of FlX, but not on
the concentration of the base. lt does not shovy deuterium isotope effect. Another
supporting evidence is the stereochemisfi of the product. Under E1 condition, the
producl is the more substituted alkene (ZaitseVs rule) as shown in Figure 11.9.

Rate=kx[RX]

ll5
Mechanism for E1 reaction. There is a close analog to Sru1 reaction called E1 reaction.
Its mechanism is given below: Spontaneous dissociation of the tertiary alkyl halide yields
an intermediate carbocation in a slow, rate-limiting step. Loss of a neighboring H* in a
fast step yields the neutral alkene. The electron pair from the C-H bond goes to form the
alkene n bond.

CH" 9Hs " ."

tA. H,o H.C
"\ @ ..o
-t
H"C-C!Ci:
65
oC - ls. ,C:CHz f
HgC
H3O,X
'
cHs cH2rH

Hsc

cH(cH3)2
CHa Menthyl chloride H

E2 condition E1 condition
@o @o
1M NaOCFI2CH3 0.01M NaOCH2CH3
oC
Ethanol, 100 80 % aqueous ethanol, 160 "C

n.cL nsc\,.t_
<LcH(cHdi^-{
l. -cH(cH3)2
cHs H

2-Menthene (100 %) 2-Menthene(32%) 3-Menthene(68%)

Figure 1 1.9 Elimination reactions of menthyl chloride. E2 conditions (strong base in pure
ethanol) lead to 2-menthene, whereas El conditions (very dilute base in aqueous
ethanol) lead to a mixture of 2-menthene and 3-menthene.
Remember! Sx2 competes with E2 and Sxi competes with EI reactions.

116
t-

Comparison of Sn2 and E2 reactions:

Reaction Favored Conditions

S*' 1. Low reaction temperatures

2. Modest to strong nucleophiles
3. Small size nucleophiles
4. Relative reactivity of alkyl halides
methyl halide > 1" > 2

E2 1. Higher reaction temperatures

2. Strong base (e.9., sodium ethoxide)
3. Bulky bases (e.9. potassium tert-butoxide). They also favor the
Hofmann Rule (the less substituted alkene) overthe ZaitseVs rule.
4. Relative reactivity of alkyl halides (3o > 2" > '1" )

1t7
 @
ca
e *1 ; "r#;:: il' ;;;t:;fr' at

(1) cH3cH2-X' LH, cfiz-.Q*c+t>c'#3

Mechanism (S*2).

c++ge(+z* - cilzc|g
ffi
m)
/DKT'I
IV
NaNH2 oo
(2) R-c-c-H R-C:C r
Na

I R'-911r- x!
I
V

R-C-C-CH,-*' * uax

Mechanism (Sr').

}\ o@
p-g-g-I R-C-C( Na * 'NHe

ls.,,q,
i
R-C-C-CH2-R' 1L

118
 oo..
Na:OCHg
(3) ,6;/\,/\..2o-H
A*Nasr
ft*,
Mechanism (St{2)

O,f,"b"",.,. ,ri*9'Nu +cH3oH

trru*otrcular Sp2
I
, leads to cyclic product
{

A*ruaar

nffis /
.z:-.,,iH
Mechanism (SN2)

^Psry

119
a

AgNO3, CH3CH2-OH
* ngcl * Hrvo.

Mechanism (S*1)
\:- H

No3
@o
'-Ag NQ, CH3CH2OH ,)e-""'""
* nscl

I
,i)-cHzcHs *orl' f) ,-ob_ cH2cH3

+
t-,tN03

r20
 H3PO4, HzQ

Mechanism (S*')

l-*,0
f,,&
Y

121
 @o..
Na: OC(CH3)3
(7) cH.cHrcHrcHr-it' ....................-.-..-.--.-.. cH3cH2cH-cn* Nax
(CH3)3COH, A
Mechanism (E2).

, @o..
Na : 0916gr;,
cn.*rrl2*r, cH3cH2cH-cH + NaX * (CH3)3COH

,f)

, Br: @
I CH3(CH2)3CEQ: 11s
(8) cH3cHcH3 cH3(cHr3c:c-H * H2C:CH-CH3

Mechanism (E2).

'ti cH3(CH2hC-c-H * nrc:cH-cH3 * ttagr

?5cHcH3
H
\
,6
Na:C-C(CH2hCH3

t22
(e) :o-H
I n2soa, A
cH3cH2c-cH3

o
Mechanism (E1).

'gff.u o-.
HSO4 \

"'-5:9
H HSO4

I
H2SO4 + CH3CH1C-CH3

o
Mechanism @1).

,l=1, 't)
CFffi-",,{
C"
'X' I

| -**
+

O-"r:"*-Q
123
Problem #l (Organic Synthesis) How would you synthesize each of the following compounds?
More t}ran one step may be required.

(r)
Gtre'Y\*(cHg)z (Fromtoluene)

CH.
t-
CH2Br
(o)",.,
o NBS, }Y
0 G"*,e
I *r., ,,
lccro
+

l^.,.,

l. NaH

z.cr*N(cHa)2

Gr_o
'9\*1"r.1,
Benadryl (an over-the counter antihistamine)

124
 (From an alcohol)

L
cH3cooH
€

(3)
o (From an alkene)

o
@o..
NBS, /rv, CCl4 Na:OEt

\-J EtoH, a

125
 o9
,n Na NH2 ,n o@
VF-\ F,*" +.NHg

z4'4.^t,
ofi
H3C-C-CH3

rr{
NBS, lnr, CCl4 KOH(aq), A,
m
erzr cazdzl
+
, B'r
/

ry 1. fon (aq) , A
2. NaNHr, A

126
(6)
(From benzythalide)
G"="e
2 Li , CuCl

(o"*1,'*'
G^0,

NBS, ftv, CCl4

..<-
KOH, a
nzQ

NBS, ftv, CCla

1. KOH, EIOH, A
2. NaNH2, A

127
 O .4...,46,4=4- (From an alcohol)

I
soBrz -/\.-z--5'H
,n ,
l ^-^.-
+

,rrFg=a_,

mffiOn-i-' I

l
'o"'

r*'
I
Y

Hsln. NaoH (aq)- -S:S^--^-.

: I

t28
 (e)

..o @
C12, hv (CH3)3CO: K
\-
+ (cHd3coH, a
+
Zn(cu)
"*',,
i* f

(r0)
44\)-
Br

Brz2 hv
+ A zLi, CuCl
(ct",,-,
(, (,

z-.-t,
I

w
I

A: ,rii, I
KOH , EIOH, A NBS, }v, cc,4
W

L 129

\
 Chapter 14 Conjugated Dienes and Ultraviolet Spec'troscopy
lntroduction.
Double or triple bonds that altemate with single bonds are called conjugated. For
example, 1,3-butadiene is a conjugated diene, whereas 1,4-pentadiene is a non-
conjugated diene.

22
sp -sp rp';rp' sp3 2
I

,,"ii'""1:::"",
I
t
H2C:CH-CH:CH2
1,3-butadiene 1,4-pentadiene
(more stable) (less stable)

Conjugated dienes are somewhat more stable than non-conjugated dienes, that is, they
release less energy on hydrogenation (experimentally) because they contain less energy
to begin with. Their stability can also be explained on the basis of somewhat stronger
bond of sp2C-sp2C versus sp2C-sp3C.

Higher-energr antibondi4g MO

fll g .,\
,€,

Two isolnled l,ower'-energy bonding MO

p orbitals

Figure 14.1 Two p orbitals combine to form two z molecular orbitals. When two
electrons occupy these orbitals, both electrons occupy the low-energy, bonding orlcital,
leading to a net lowering of energy and formation of a stabte bond. The asterisk on 92'
indicates an antibonding orbital.

130
 t- .1t4" TffiISffi Antibonding MO (three nodes)

@iifi@ir

I ,. lh* Antibonding MO (two nodes)

++++ ( -
Four isolatod
p orbitale ".-.1p ,f- {,2 BondingMo(onenode)

\
\
#ffi
\,-p *, BondingMo(nonodes)

ffi
Figure 14.2 Four z molecular orbitals in 1,3-butdiene. Notice that the number of nodes
(a region of zero electron density) between carlcon nuclei increases as the energy level
of the orbital increases.

Reac'tions of conjugated dienes:

(1) They undergo electrophilic addition reactions as shown below:

t3t
 HBr, 0 oC
H2C-911-CH-CH2 'tt
H2C-911-CH-CH2
I
HBr
l rrr, 40oc Kinetic control
I

*
H2C-C1-1:CH-CH2
HBr
Thermodynamic control

Mechanism.

H'?crTr-":-"" (at 0 oc)

\ftG,1 I

@+ -tt
Hzg-QH-CH-CH2
",?-r-cH-cH2
H\ H tB-rt

tBr: (1,2-addition)

HzcfcH-cH-cH2 (at+O'C)

\l,*cl,-l I

@ n
v
eni,
-l o;'
H2C-CH-:--CH*CH2 <-> H2C-CH-CH-CH2
-l
ti ;EI' H I

-l
HrC-CH-CH_CH"
I'
H .qI,

(1,4-addition)

132
 l{rnetic control
Thermodlmamic control

fi
Beaetion progress ----------t

Figure 14.3 A reaction energy diagram for two competing reactions in which the less
stable product (B) forms faster than the more stabte product (C). These two products are
known as kinetic and thermodynamic control.

BTCH2CII:CHCHg
(1,4 artdust)

Reaction pnogyess+>
Figure 14.4 Reaction energy diagram forthe electrophilic addition of HBrto 1,&
butadiene. The 1,2 adduct is the kinetic product because it forms faster having lower
energy of activation (AGl, but the 1,4 adduct is the thermodynamic product because it is
more stable since it contains lower energy.

133
t.

An analogy for Kinetic Control:

lmagine a very disoriented steer stumbling randomly around a pasture with a shallow
watering hole and a deep wellwith a high fence around it. Where is the person likely to
end up? Certainly the deep well is the state of lowest potential energy. However,
because of the fence around the well, it is simply less likely that the animalwill fall into
the well; the person is much more likely to wander into the watering hole. Now, if you
imagine a large herd of similarly disoriented steers staggering around the same (very
large) pasture, you should get a reasonably good image of kinetic control. Most of the
animals wander into watering hole, even though this is not the state of lowest potential
energy.
(2) Conjugated dienes undergo Diels-Alder reaction: lt is a reaction between a
conjugated diene and an alkene or an alkyne (dienophile = "diene love/') to produce
substituted cyclohexene or nonconjugated cyclohexadiene, respectively, as shown
below:

:o;

OA heat

GS)

nooMe
\rl COOMe
(..il1*"""

t34
Table 14.1 List of some dienophiles that are used for D-A reactions.

or- 06-

f
*t-"-"] H--"9P*-, il
,_#F.-OCHzCH3
il ll

Ir-x-*] ,-c-* Ir-C-H

Etlrylene: PmPeuoI Ethyl proprsns.l.
unreactivt (Acrolsin) (EthVI acryfah)

o o
il osrroB'
H-.;- il
-c- C H- 4iC:N
I \
'-i2*-c-H
illl lt
0
I
H/c*'- C
il
n-"+c-"-, H-c-lt
llt
c
ll
o. o H
I

Maleic anhydride Benroqulnone Propencmitrlle Meetl

(Acr;doniirile) pnopfmmte
Featurcs: of DiA rcactions:
(1) One cfiaracteristic feature of Diels-Alder reaction is that it is a single step reaction Ma
a cyclic TS that does not invslve anyrintermediate.

(2) The,sgco,nd feature is that it is stereospecific reaction, meaning that the

ster:eoChernistly of the starting dienophile is r,etained during the reaction in the product.
Thus, it,,produces a single stereoisomer. Two such examples are shown below:

H-r7-cw H-"-corctt, H

l+ll Irl
-,,\L.COzCHi
Vf-cH"
H-"oc*, ,-"-"*, H
1,.&Butadiene Uethyl (2-2-b'uteaoete Cie product

H-azffi' H--c'-co2crl3 H
-,{-COzCHs
f+ ll- III
\4,n
,-"o"*, ,rc-t-* HsC

l,&Butafieuc Methyl (E)-2 -butenoate Trens protuct

135
(3) The third stereochemical feature is that, when the D-A adduct is a bicyclic compound,
the adduct has endo stereochemistry rather than exo stereochemistry as shown below
with an example:

}J

Exo product
LNOT fonnedl
0 Endoproduct
Maleic anhydride

The endo product results in this reaction because there is a better orbital overlap
between diene and dienophile when these two partners lie directly on top of each other
so that the electron-withdrawing subsUtutent on the dienophile is undemeath the diene.
(4) The diene must adopt what is called s-cis conformation ("cis-tike" about a single
bond) to undergo the D-A reactions. Only in the s-cis conformation are carbons 1 and 4
of the diene close enough to react with an alkene through a cyclic transition state. The s-
b oorforrnation of the diene cannot react with an alkene to give D-A product.
Figure 14.5 shows two such dienes that cannot participate in D-A reactions.

m
H H
H\ -rC
I
H\ I

c'-' C--<-c.- CH,

H*C-.-*r't-*
I I

\a-zc-.-cr'c-H c.-
H.,
lt
HH I
H
I
H
Abieyclic diene SeYere sterie strain (2Z,tlZl-Hex,'die,.e
kigid c-trans dieue) in s-cis fonn (s-trans, more stable)

Figure 14.5 shows two dienes that cannot participate in D-A reactions because of s-
trans conformation.

136
Ultraviolet (UV) Spec'troscopy (200 nm400 nm). lt is a method for the struciure
determination of conjug?ted rnolecules. When a conjugated rnolecule is inadiated with
UV light, energy absorption occurs and a z-electron is promoted from the highest
occupied molecular orloital (HOMO) to the lowest unoccupied molecular orbital (LUMO).
For 1',3-butadiene, radiation of l,n'o= 217 nm is required. As a general rule, the greater
the extent of conjugation, the less the energy needs for the transiUon frorn HOMO to
LUMO (that is, the longer the wavelength of radiation required).

/- {t"

. ,ls* LUMO T*

++++ ./,
'i -
lw
GfV irradiation)

*z HOMO
Fourp atomic --{-
orbitals
'..+t_ *t
+1-
Ground-state Excited-state
electronic eleetrotric
configuration configtrration

Figure 14.6 UV excitation of 1,3-butadiene results in the promotion of a r--electron from

HOMO to LUMO.

1.0

f,m = 21? nm

,o
g
.l
.o
L
'o
B

20a 220 z,LO 2ft0 2N 300 320 340 360 380

Wavelength (nm)..*
Figure 14.7 The UV spectrum of 1,3-butadiene has a l.',* = 217 n

137
 o.7

0^6

(u
I
cd
p
!
@

B-Carotene

Figure 14.8 UV spectrum of p+arotene that contains 11 conjugated double bonds. lt

absorbs visible light (400 nm-800 nm) having ? X,n* = 455 nm.

White light from the sun or from a lamp consists of all wavelengths in the visible region.
When it strikes p-+arotene, the wavelengths from 400-500 nm are absorbed, while all
other wavelengths are transmitted and can reach our eyes. We, therefore, see the white
light with the blue removed, and we perceive a yellow-orange color for p-carotene
(complementary color). What is true for carotene is also true for all other colored organic
compounds. All have an extended system of zr electron conjugation that gives rise to an
absorption in the visible region of the electromagnetic spectrum.

Otto Paul Hermann Diels was a Professo-r of Chemistry and shared the 1950 Nobel
Prize in Chemistry with one of his research students, KurtAlder, who was a Professor of
Chemistry at the University of Cologne for the so-called Diels-Alder reactions.

138
 Chapter 15 Benzene and Aromaticity

lntroduction. Benzene and its structurally related compounds are called aromatic
compounds; their chemical properties are totally different from most other organic
compounds, which are collectively called aliphatic compounds (alkanes, alkenes,
alkynes, alcohols, alkyl halides, acetone, and acetic acid). Table 15.1 shows the
contrasting reactions of benzene and alkene indicating the difference in reactivity
between them.

Table 15.1 Contrasting reactions of benzene and cyclohexene

X:

HX

,. Blz Br
> (Addition reaction)
H
H2, Pt, EIOH
KMn04 l atm, at}5oc
o-o
H3O:X:

Hooc,*CooH

Br2, FeBr3 H2, Pt , EIOH

150 atm, at25oC

Br

d*Hsr
(Substitution reaction)

t39
 Table 15.2 Common Names of Some Aromatic Compounds

Formula Name Formula Name

Toluene Benzaltlehyde
(bp 111"C) (bp 178"C)

L
cooH
Phenol Benzoic acid
(mp 43'C) (mp 122oC)

NH,
Aniiiae Benzonitrile
(bp 184"C) (bp 191'C)

o
ll
CHg
Acetophenone orf}o-Xyleus
(['='* (mp 2l'C) Gp 1aa"C)
CHr

?o, :CHZ
CHCHs
Cumene
(bp 152'C) e, Styrene
(bp 145"C)

140
Table 15.3 Some Common NSAID (nonsteroidal anti-inflammatory drugs) that also
contain aromatic rings in their chemical structures.

?n. ,F, 9H, ?n.

ry"*' ooccru
cH3-cHCHrn_trcHcooH

(Aspirin) Ibuprofen
,.""qg"HcooH
(Advil, MoEin, Nuprin) (Naprosyn, Aleve)

1,&Cycloheradiene

Cydoherene
o
cyclohexene
O
Figure 15.1 A comparison of the heats of hydrogenation of cyclohexene, 1,$
cyclohexadiene, and benzene. Benzene is 150 kl/mol (36 KcaUmol) more stable than
might be erpeeted',for "cyclohexatriene'.

A collection of pr,opedies that are associated with benzene and benzene.like compounds
is ca[ed aromaticity. Aro-matic cornpounds (benzene is a parent compound for all
arornatic cornpsunds)'have the foflowing characteristics:

(1) Aror,natic @mpounds are cyclic, planar, and conjugated.

(2) Arornatic comp-ounds have resonance stabilization energy of varying amounts

dependtng, on fie stnrctures:of. arornatic compounds and, therefore, stable. For example,
benzene has resonance stabilization energy of 150 kJ/mol(36 KcaUmol).

(3) They react witr electrophiles to give substitution products, in whictr cyclic conjugation
retained, rather than addition products, in which conjugation is destnoyed.

t4t
(4) They have a HUckel number of electrons 4n+2, which are delocalized over the entire
ring.

Cyclic, planar, conjugated molecules with other number of zr electrons are antiaromatic.

Aromatic lons. According to the Htrckel criteria for aromaticity, a molecule must be
cyclic, conjugated (that is, nearly planar and have a p orbital on each carbon, and have
4n + 2 n electrons. This 4n + 2 rule is broadly applicable to many kinds of molecules,
not just neutral aromatic hydrocarbons. Here are a few examples of ionic aromatic
compounds:
..o ..o f rvr
o 'x'
o-o
Mo

A-A
'T'

I II
..o Kr" rtK
'ta rXr 2K@

o -@
III
o-@ w

A ov VI
oVII vIII

All of the ionic organic compounds, (l-lV), are aromatic compounds, since they fulfill the
requirements for aromaticity. On the other hand, their corresponding neutral organic
compounds (V-Vlll) are not aromatic. The reasons are as follows: V and VII follow 4n + 2
n electrons, but are not planar because of the presence of sp3-C in their structures. Vl
neither follows 4n + 2 z electrons nor is planar because of the presence of sp3-C in its
structure. Vlll neither follows 4n + 2 n electrons nor is planar because it is a tub-shaped
molecule.

Heterocyclic Aromatic Compounds. Heterocyclic compounds can be aromatic too. A

heterocyclic compound is a cyclic compound that contain an atom or atoms other than
carbon atom in its ring. The heteroatom is often N, O, but P, S and other elements are
also found. Here are the following several examples of heterocyclic aromatic
compounds. ln many drugs, there are heterocyclic aromatic structures that make up their
chemical structures.

t42
O ra -N-
/-\
-o'
I
H

Pyridine Pyrrole Furan

Antibondin;

Sixp atomic orbitals

t. 0s {s
<ry
es
€@
tr ll
TT Bondiug
l,tlt

Six benzene moleeular orbitals

Figure 15.2 The six zr molecular orbitals of benzene.

Clclototdayl ctim
ah raiahoa

143
a

sp2+ybddired

* "S )
"mg)" @-r*

qp'*bit l
Sir z electrcm

IaE pair i!
p qbital

H\B )
'8m W"

Sh r clcirons

Figure 15.3 An orbitalview of some aromatic compounds (cyclopentadienyl anion,

cycloheptatrienyl cation, pyridine, pynole and thiophene).

Experimentally, the signals of aromatic hydrogen nuclei (also called protons) appear at
6.5-8.0 ppm and those of vinylic (alkene) hydrogen nuclei appear at 4.$6-5 ppm in the
nuclear magnetic resonance (NMR) spectra:

1,44
 Chapter 16 Chemistry of Benzene: Electrophilic Aromatic Substitution
(Ars')

lntroduc'tion: The most common reaction of aromatic compounds is electrophilic

aromatic substitution. ln this reaction, an electrophile (E.) reacts with an aromatic ring
and substitutes for one of the hydrogen atoms:

O+fA"-ry=*r^
Many different substituents can be introduced onto the aromatic ring by this reaction.
These are halogenation, nitration, sulfonation, Friedel-Crafts (F-C) alkylation, and F-C
acylation. The general mechanism for all of these substitution reactions can be
represented as follows:
Mechanism.
trE

O\-f^"# Qfl,'f *O'+HA

(=
t
N=
olsy'
-
I
:U,
Intermediate

6=

145
L- (1) Halogenation (with XzlFe)G) reaction produces halobenzene:

L
:Br:
L
Brz,FeBrs-0*Her*FeBr3
. O
: Mechanism.

+ HFeBra

( Her * rear. )

146
a
o
a
a
f (2) Nitration (with conc. HNOs and conc. HzSO+) produces nitrobenzene:
j Noz
t ConC HNO3

t conc H2SOa

l? Mechanism.
t-
\- ,fh @o \a/o'
'[j.**
H-O-N.
- \-o +
\-
O!
HHSO4

-
'i--s
H-
:o:
,_g__,

( E@)
:o: :O:

t3^fl;*eF,\ + ^ -ll ..o

(9N-o:

(/ * n,soo
\,/ ,8, VJ@ ' 'i
HSo4
lll
Noz

l. Zn, conc HCI

2. NaOH (aq)

o ..o
l. SnCl2 , H3Q I Cl :

2. NaOH (aq)

(yo"'

t47
a

(3) Sulfonation (with SOg, conc. HzSOn) produces sulfonic acid:

so3H
SO3, H2SOa
+ H2SO4
( Fuming H2SO4 )

Mechanism.

HHSO4 ----'-'--"'->

I
so3H
+ H2SOa

y'\tsostt l. Naol-l, 3oo oc Z ,\(8-*

(/ (/

148
a

(4) Friedel-Crafts alkylation reaction (with R-Cl, AlCl3) produces alkylbenzene:

* n-x * Hcl * Rtct.

o,
where, RX: lo ,2o,3 allylic and benzylic halide

Mechanism.

bo
eF'\t
I
?''''

* Hct * nlct.

CH"

Alcl3

O + H3c-?H-cH3 O"'-"*' *ncr *nrcr,

149
Li mitations of Friedel-Grafts alkylation reaction :

(a) Aromatic halides and vinyl halides are not used in this reaction, since aryl and vinyl
cations are too high in energy to form under F-C conditions.

(b) An aromatic ring containing either by an amino- group or by a strongly electron-

withdrawing group does not undergo F-C alkylation reaction.

Table 16.1 List of aromatic substrates (or compounds) that do not undergo F-C
alkylation reaction.

d + tt -.-x )\11.:11
, $10 yea"cttan where v =
-frn,
*No.r, *CN,
.* sol,H, *cr{o, * c0cH{,,
_COOH, _COOCHs
(*NHu,-NH&-N&)

(c) F-C alkylation reaction often undergoes polyalkylation reaction as shown below:

O * (cn.).cct
Atct3

d"**6*
c(cH3)3
major minor

(d) ln F-C alkylation reaction, there is always a chance of skeletal rearrangement of the
alkyl group, particularly when 1o and 2' alkyl halides are used as shown below:
Remember! Carbocation intermediate chemistry is always associated with
rearrangement reaction, whenever possible.

150
a

(d) ln F-C alkylation reaction, there is always a chance of skeletal rearrangement of the
alkyl group, particularly when 1" and 2" alkyl halides are used as shown below:
Remember! Carbocation intermediate chemistry is always associated with
rearrangement reaction, whenever possible.

O * cn.*qcH2-cr
Alc13
* Hcr * nct.

CH3CH2CH2 - - -AlCl3 o
+ Atc14
66 @

"lJ'
CH3CH9Hz ---Cl---AlCl3 + -l
H"C-CH-CHc
H H

e$:\
o CH"
Atct4
-@
"l
H"C-CH-CHr
H o
AlCla

CH.
-cHs
O * nq * Rcr.

ln addition to AllG, there are several other Lewis acids that are used as F-C catalysts
for this reaction. Their order of effectiveness has been shown to be:

AlCl3 > FeCls> BFs > TiCl3 > ZnClz> SnCla

151
(5) Friedel-Crafts acylation reaction (with either RCOCI, AlCls orArCOCl, AlCl3)
produces atkylaryl ketone and diaryl ketone, respectively. ln this reaction, the
electrophile is a stable acylium ion that does not undergo reanangement, which is in
contrast to carbocation intermediate.
:o:
ll
Alct3
*-B-",+
O e)-"-. * nrct. * Hcr

Mechanism.

Acylium ion
-o

+eF;\
({) t?,
:O: :o: o
lt
R-C-CI- - -AtCt3 +R-Co tl
+ Atct4

\
to n'"ta
I
+

* nrcr. * ncr

:o
il
, o
t-
\//
il +
"r."nr-8-c'
Atct3
e)'"-cH2cH3
I
HztPd znlngy, conc HCt
I
c2H5oH +
CH2CH2CH3

Ctr",,CH2CH3
This reagent HzlPd, ethanol only works
for alkyl aryl ketones.

152
a

Activating and Deactivating Groups. The substituent (group) already present onto an
aromatic ring affects the reactivity of this aromatic compound towards further
electrophilic substitution reaction. The electron-donating groups (either through
resonance or by their combined inductive and hyperconjugation effects) activate the ring
towards this reaction (ArsE), that is, reaction rate is faster than benzene itself). The
electron-withdrawing groups make the ring less reactive than benzene towards this
reaction what are called ring-deactivating groups. The hydroxyl group in phenol is a ring-
activating group, while nitro group in nitrobenzene is a ring-deactivation group. The
substituent already present in an aromatic compound can also direct the incoming group
either to the ortho- and para-positions or to the meta-position. These substituents
(groups) can be classified into 3 groups: ortho- and para-directive activators, ortho-
and para-directive deactivators, and meta_-directing deactivators. Table 16.1 shows
the classification of substituent effects in ArsE. All activating groups arc o- and p-
directing, and all deactivating groups other than halogens are meta-directing. The
halogens are unique in being deactivating but o- and pdirecting. The explanations on
the basis of stability of carbocation intermediates are shown in Figure 16.1-16.5.

Table 16.2 shows the classification of substituent effects in ArsE

P9
-NHz -QcH, -CHs(alkyl) -i' -qJ' -C-u -C-oH -So3H -No,

, -0, -ntHcocn.:Q-, ++
-Cl: -l: -c-ocH3
\o -t-cn.
o -c=N-NRs
)
Ortho- and para-directing Ortho-and
Y-
activators para-directing Meta-directing deactivators
deactivators

153
 r f.,;;_l CH"
?fr, | "n
ftho
""1#.-"'l-.d"* ef*o'
I
t-IMost stable I
ir,l flL f'"
ft..,*
O
Meh' 3% (-L" NOr
q+" -
NO,
d,,
* Nor

QHt CH,

A
I

st% ;,f\
Y-
H NO2
-
m-
Figure 16.1 Carbocation lntermediate (also known as Wheland intermediate) in the
H NO2

nitration of toluene. The o- and p- intermediates are more stable than the m-intermediate
because the positive charge is on a 3o carbon rather than a 2" carbon.

<*?", FP," -.-l :OE

'iin
*,,bi,-"'-kl -.UNo2-G*o, lHls

:OH ,iiu :OII ,<iH

,'(
I

z.5. .,( ,,\

IJ
\7
ldcta
atlssk
l o%
(-.1-"
Nor
Q+" Noe
ll_/"
* No,
Phonol \
\
\ ,iin
\\ I
C?H
\--P"r" u* ;f\ ra\
-
ffi-fi"
attact

nYnt,
"Voro,

154
Figure 16.2 Carbocation intermediales in the nitra$on of phenol. The o- and.p-
int-brmediates are more stable than the m-intermediate because resonance donation of
electrons from orygen.
,ci, :Cl;

I
rR ftho
-bxo,*6!u
/
I ,ct,
:Cl:

,\
U
I
Urt A--
(,-k$o
,ii,
-A
:Cl:

-(
, - \-l.,To, -
,
atlacl
'" *^i",
Chlor-
bcnrcno \
\
\ -J?i',
\
\-r'g **A ._
attr&
\c
II NOe rr Noz H NO,

Figure 16.3 Carbocation lntermediate in the nitration of chlorobenzene. The o- and p-

intermediates are rnor€ stable than the mintermediate because resonance donation of
electrons from'halogen lone"-pak of eledrcns.

r
cHo cHo
cHo
IH IE ls
h{-a
Ortho

U"
kaststaH6
-*Q) - (.,J.

'-o*5*-u I cHo cHo CHO

e-
I ,,\
o \
Borddehvilo
--=ffi--
M.ta
72%
ts+
d.- \^#
\ cHo CHO

A
I

\-=- /\
Y-
9%

HgI Hcl

155
Figure 16.4 Carbocation intermediate in the chlorination of benzaldehyde. The m-
intermediate is more stable than the o- or p-intermediate, since the latter intermediate
there is a development of positive charge on the neighboring carbon atoms. This causes
a repulsive interaction causing a too high energy intermediate for o- and p-intermediates.

A summary of the activating or deactivating and directing effects of substituents in ArsE

reaction is shown in Table 16.3

Substituent Reactivity Orientation lnductive effect Resonance effect

Activating Or&o, para Weak; None

-cHs
electron donating-

Activating Ortho, para Weak;

-on, Strong;
elechon-withdrawing electrondonating
-ftH,
Deactivating Ortho, para Shong; Weak;
-E', -c-l ',
electron-withdrawing electrondonating
:
-Q.r:, -.1
o
Deactivating Meta Stong; None
-N(CH3)3
electron-withdrawing

-NOz, -CN, Deactivating Meta Stong Strong;

electron-withdrawing electron-withdrawing
-cHo, -cqcH3,
-cocH3, -cooH
Combined directive etfect of two or more than two substituents. When there are two
groups onto an aromatic ring, and one is o- and p-directing and the other is m-directing,
the one that is strongly activating and o- and p-directing will determine the orientation of
the incoming electrophile. For example, 2-fluorometho>rybenzene is nitrated at o- and p-
positions to the methory group.

#' conc. HNO3

conc. H2SO4

Noz
+ "'-(y'

Prefened positions most likely to undergo electrophilic substitution in three isomers of

nitrotoluene are indicated by anows.

156
*&* -'f..,
+ Noz
t
I (ortho-) tr (meta) III (para-)

(l) CH3directs E* to o- and p- positions with respect to itself, both the positions are also
m- with respect to -NOz.

(ll) The o- and p-directing group controls the orientation.

also m- with respect to

(llD E. is directed to o-positions with respect to
-CHs, which is -
NOz.

When both groups are o- and pdirecting and they are in opposition, the more strongly
activating one controls the orientation as shown below with an example.

@o

#
EA

CHs

Nucteophilic Aromatic Substitution (ArsNu) Reaction. Aromatic halides that have

electron-withdrawing substituents (-NOz, -CO- or-CN) usually undergo this type of
reaction. Such an example with mechanism is shown below:

NOz OzN
1. NaOH
* ttacl
2. H3O:X:
Noz

Mechanism. (Basicalty, it involves two steps: the first step is the nucleophilic addition of
hydroxide ion to the electron-poor aromatic ring, producing a resonance stabilized
-
carbanion intermediate (also known as Meisenheimer complex) and the second step is
the elimination of chloride ion from the Meisenheimer complex giving the substitution
product. (ln short, ArsNu is the nucleophilic addition-elimination reaction).

1s7
 Noz

Noz

IlHgg'c.J'
. ..o
+

'o-n

Arsuu occurs only if the aromatic ring has an electron-withdrawing substituent in a

por1ion o- and p- to tn" halogen. The more such substituents there are, the faster the
reaction goes.

158
Ortho
Nor
-:()ll
------.-.--.
130"c

fi
CI OH CI OH
Para
X
ft+,++ Y N[]z N02
+_..+
v
-:().i/\ l0:*
N*

Metafu
N {-}:r

CI OH

No stabilization
ofcharge bY
nitro grouP
NOT fom*d
Only the o- and p- intermediate
Figure 16.5 ArsN, reactions on nitrochlorobenzenes.
so only the o- and p-isomers
carbanions (but not the m) are resonance stabilized,
undergo this reaction.
erectron-withdrawing substituents
Ar"n, by benzyne mechanism. Aryr harides without
At high temperature_and pressure,
do not reactwith nucleophiles undir most conditions. oC and 2500 psi
NaOH (aq) at.340
even chlorobenzene can be forced to reacl with
pi"rrrr". The reaaion along with its mechanism is shown below:

159
a

:o-H

o
I

1. trtaott (aq), 340oC, 2500psi

@ ..o
+ Nact
2. H3O:Xr

't5- ,.1
ry"
r'rirep
O)*Hzi*ruac
Na ,9H

@@..
Na :OH

I @
,6-H
..oNa

d
9' @ ..o

ry a HzQ
H3O:X:
+ NaX

160
 14C1-)
Two evidences for the benzyne mechanism: Bromobenzene with radioactive at the
C1 position on reacting with NaNH2 that produces two products of equal amount (50%
each), shown below, suggesting a symmetrical intermediate in which C1 and C2 are
equivalent. This requirement can be met with the benzyne intermediate.

Cr'" itr
Srollrobauzena
[ o]
Benzyno
N':'
er*"'. G**,
tsyumctrlasl) AniUne

The second evidence comes from the trapping experiment. When furan is added to this
reaction, D-A adduct (shown below) is isolated indicating the strong evidence for
benzyne mechanism (dienophile). An orbita! view of this very reactive intermediate is
shown in Figure 16.6

a\
lo
v
ryt'
KNH2

oo
ill

tu
:o:
D-A reaction

t
t
t
a
i
I
t
a

Stateo Yles,
Sldeview

Figure 16.6 An orbital view of benzyne-a highly distorted alkyne. An alkyne triple bond
,rir sp hybridized carbon atoms, but the benzyne triple bond uses sp2 hybridized
carbon atoms. A typical alkyne bond has two mutually perpendicular bonds formed by p-
p orbital overlap, but the benzyne trip-le bond has one bond formed by p-p orbital overlap
and the other bond formed by sp2-sp2 hybridized orbital overlap, which lies in the plane
of the ring and is very week because of poor overlap.

161
Oxidation of alkylbenzenes produces benzoic acid'

CH.
" KMnO4

@ ..O
,a
A
H39'X'

KMnOa

@-OA
* co, + Hri
Hg9'X' ,A

KMnOa
No reaction
@ ..e
,A
A
He9'X'

to occur'
The presence of benzylic hydrogen is essential for this oxidation

fr
of this reaction is
Benzylic bromination of alkylbenzenes by NBS (Mechanism
discussed in ChaPter 10)
:Br:
NBS, ftY
cc14

Reduction of aromatic Gompounds: (with HzlPt or Na/NHa, EIOH)

(a)

\4",.ffi
Pt' EtoH
AlcHt H2
'
u"r,
| ,r, *n,", =,o*
u,*, zs"c
|,

CX*.

162
a

(b)

O
Naar.H3, EtoH >
o
,ci-cH.
t"
'6-cH.
\-- lA
\)
Nan{H3, EtoH >
b
cooH cooH

d
I

;f1 NaaIH3, EtoH >

\2
€ *O
Mechanism.

-r}R, oe\,
Na\

CH3CH2-QaH
^)

@
*

o'\
Na
..o o
* cn.cHr9,t',ta
I

A/
ctt.cttr-9rn

o *
..o
cn.cHro:
@
Na

163
,

Mechanism.

,y"T ,ti_cHs

o\
lNa I

( cn'cn'si*3

^)
CH3CH2-OrH

I
V ^Ol*

6: ..o
CH3CH2O: Na
@

164
 Mechanism.

cooH

A
x'*"
.Al
L CH3CH ,-oJH

I
cooH
Na. li it ..o

+
@
|! !J *cn3cn2p.,rui
H

"f-r.C,fr-O1#
I

l -
Y
cooH

d * cn3cn20?*3

165
Problem #1. (Organic Synthesis) How would you synthesize each of the following compounds?
More than one step may be required.

(1) H2N

'?-"" '?"t'
HNo. o"
O
clz'Fecla
- conc.

a
tC.l'
conc. H2SOa

:Cl ;

+
,OCtt3
l
AzCl
tt
\4 J H2, Ni

(ortho-isomer needs to be separated)

This is a 3-step synthesis.

t66
 6
SO3, ConC. H2SOa conc. HNO3
conc, H2SOa

S03H
(sole produ ct)
conc. H2SO4

AI
I

o'*ff*o'

Clz, feCf. I

q :Cl :

*,-,
I
: OCH"

-,U
v
NHz

,Cl :

This a 5-step synthesis.

167
a

a) : Br:

+ cooH
(From benzene)

: Br:
Br2 , FeBr3

d cH3cl, Alcl3

(ortho-isomer needs to be separated)

OR
9Hg

o cH3cl, Alcl3
0 Br2, FeBr3

cHs
(ortho-isomer needs to be separated)

CI2, FeCl3

conc. HNO3
conc. H2SO4

(This compound nds to be separated from the desired compound.)

168
7

9Hs gHg
cHscr,Arcrs-d#d*o,*
9He

#Noz

FeBr3 I

lrro, FeBr3

+
Noz
'*qu" 9H.

Noz

#
cooH
(From benzene)

?,,
cH3ct, Alcl3 ,4, conc. HNo3

\) *rrjr"so,
#Noz
@ ..o
l^rnoo , H3o:X:
- lrs'c
t
cooH

#
Zn, conc. HCI

: NHz
+ Noz

169
(6) CH=CHCHs

(From benzene)

:o:
:o:
il
ll
CH3cH2-C-el, AlCl3

ry"-cH2cH3
| ,r, ,0, =,o*
I

ry""cH2cH3
I -"",.
",r,
I

'u'QcH2cH2cH3
INes, l,
I c"'o
I
cHcH2cH3

@o..
K:OC(CHj3
(CHd3COH (solvent)

This is a 5-step synthesis. ,*DcH=cHCHg

170
 (7) HO-CH-cH3 cH2cH zoH

d d (From benzene)

cH2cH3 [l-"r.
\- cHgcHzcr,Arcrg_d#d
o
.9@
(CH3)3CO:K

(ctt.).con, A

cH2cH2oH

0 2. NaOH (aq), H2O2

l. Hg(OAc)2 , HzO

J. NaBH4

'OH
I

6"-

171
*'m (Naphthalene)

:o:
Zn (Hg), conc HCI

o\cooH encooH
I .o"o
I

o?*, I

Intamolecular F-C acylation reaction I o,",.

+

m
Zn

tw,cct4
(Hs)' conc HCI

w :o:

l-r.,

: Br:
NaOEt, EIOH, A
m
l*r", hv, ccta

d
,rii'
NaOEt, EIOH, A

172
 (From benzene)

)ur:, Arcr3
conc. HNO3
conc. H2SOa
0c
&-,.,
30
(Yield 16%)

Better synthesis:

F
SO3, COnC. H2SOa conc. HNO3

#
so3H
conc. H2SO4

so3H

H2S04

Hzo
A

Y
ry*o'
(higher yield)

173
 (10) 'l'lHz

ry-"' 1r.o* aniline)

:O:
il
:NH- c-cH3
'NHz

d
cftcocl, Q
o
l ro., conc. H2soa

I
:Q 2

t1
:NH-C -cHs

+ SO3H

I HNo3
"onr.
| H2soa
"or".
+
!- :O:
il
,NH-C-CHs

q-"
SOgH

| ,. ,rroo, Hzo, A
I z. n"on t"q)
t
:NHa
t-

ry*o'
o-Nitroaniline

174
a: