дмТе

ф еб=азодл
2- Е2

Е) Р.та±л

Ва В. p:ocew
Е}
ofa arbocation halide
tbe baseto fcxm Те а1Епе-
:
frst order kinetics fe— cf Те —у

леде, Е1 mechanismis tcrmed as unim01ecular as

д ду ос mdecu1eun±goes соп1епсу change.

(1)

AJkyl halide ha1ideion Carbocatim

+ н:в
Basc
 Of articChemist I PU)

above reactions are dehydrohalogenation

of alkyl
yield an alkene halide

C2H,OH
eg. CH. C — Br

CH—Y + C2HséH
CHFC—CH
+ C2HOH%
CH3
10.3.1 Orientation
When there is a possibility of more one alkene then the
product is governed by Saytzeff orientation i.e. the most branched of
is the most

CH3 CHA
c;Hs0H
c—CH3 +

tert - pentyl bromide 2- Methyl -2- butene

(Major product)

From the heat of combustion, it is known that olefin stabilityincrease

substitution, thus El reaction occur under thermodynamic control, the most stableproduct
preferred product.

C2HsOH
2)
2-butene 1-butene
2 bromobutane
(Major product)

10.3.2 Evidence for El Mechanism

order kinetics also .
Elimination reaction that follow first
hydrogen isotopeeffectastheprotonisk*
(1) not accompanied by a primary brokeninthcrate
been
fast step, If the VB-carbon-hydrogenbond had
second, E2 eliminauon.
observed as in the
have been
step, isotope effect could
 (\ictates the гатеof теасиоп ечв
itse\f by геагтапдстос0\of thc alVyl двор.
[0 carbocation than whtch 'я genevated 'thts ечьЫ
also obtained повз thc rcactaI\t3that во мя цяатп •

СНВ сн,

сн,

сн
СНГ
сн,снз
снз—сн:с= СН _ СНГ — С — СНА

(Моге stable carbocaion)

снзсн,
снзснз
сн,снз rearrangement
-ддщ. снз —с—сн
сщ-с-сн снг
снз
снзвт (30 carbocation)
(20 carbocation)

снзснз
снз снз

Reaction
t13FactorsAffecting ЕЯ
influence the rate ofEl reaction аге
that
Diferentfactors
depcndsоп the
so tate 0f
is the in El stabiliset* carbocatm.
+1 effect would
ofthe carbocation formed, groups
-with
elimintion in orderхо
readily undergo
апуstericallystrained molecule would
lectease
the strain.
ofstabilityof carbocation
 Pharmaceutical Organic Chemistry - I (PO) 10-6

Therefore order of reactivity is substrates. But

bridged halides
non cannot
geometry and is highly strained assumea
Nature and concentration of the base : Platq
(2)
El reaction are independent of nature and concentration
of the base
ally in the form
(3) Nature of leaving group : of the
solvent
Least basic groups are good leaving groups, thus order
of leaving
group
Vltv

(4) Nature of solvent :

Rate of reaction of El reaction increases by using polar
solvents
intermediate.But SNI reactionare usually favouredover El dueto the
polarity and low nucleophilicity favour El reactions.
reaction.
Solvents
of
(5) Temperature :
Increase in temperature favours E I reaction and hence increases
the rateofreaction
activation energies of elimination are higher than those of the
substitution
reaction.
10.4 E2 Mechanism
• Evidences
Orientation
• Stereochemistry of E2 —Antielimination Reaction
• Factors affecting rate of E2 reaction

When an alkyl ed it followeda secondorder kiN

and reaction sfiÖWÜÖconcerted mechanism i.e. the reactionis ayv.$gmrgactionmol
bond breaking and >ond Rate depended both on

concentrauon of alkyl halide and the base therefore a

H Base Alkene
Alkyl halide
K. Rate constant
Rate of reaction= K[RXI [:BI
HBr+
+ C2Hsoe—+
I -Propene

2-Bromopropane
 10-7 Elrrr1inatV1Reactons
- I (PU)
Chemistry
øniC

kinetics.
ad order
This is consistentwith a mechanismuhich does
not take place :
indicating the reaction to be a single step
tion as intermediate thus
carboca

Isotope have different mass and also do not

hydrogen isotope effect.
they differ in the rate of reaction. So the difference in
iCalchemical pcoperties,
due to a difference in the isotope present in the reactant is called an
ofreaction
rate
Isotopeeffect due to the breaking of a bond to the isotopic atom are called
effect
. effect'/
elimination reaction is carned out by replacing hydrogen v.ith its isotope
an
Breaking a carbon-deuterium bond is slower than
the reaction slows down.
bondz)
a similarcarbon-hydrogen

C=C +H—Z+X
Base x
(Alkene)
(Alkvlhalkie
withfiydrogen)

C=C +D—Z+X
x Base x
(Alkylhahde with
(Alkeoe)
or deuterium)

Peofreaction with hydrogen

in the alkyl halide
Rateofreaction
with deutenurn in the alkyl halide
Reaction
for
ordinaryhydrogen is 5-8 times that
for the deuterium
can be measured
in two ways :
tmermolecular
compete competition, a mixture of labelled and
for a limited unlabelled
amount of reagent and the relative
Q) • measuredthus arnmmtof the
In indicating the rate of the reaction.
competition, a single
the reactant is used in which some equivalent
and others not labelled.
reaction. Ofproduct ts studied
thus showing the reaction site ant
the rate the
'f
 Pharmaceutical Organic Chemistry - I (PO) 10-8

Let us consider dehydrohalogenauon of 2-phenylethyl

and of labelled 2-phenylethyl bromide which contains
bromide
deuterium
at both

+ C2HsONa
C6HsCH— CH:
+

2-phenyl ethyl bromide

+ C2HsONa C6HsCD= CH
C2H,0H

labeled 2-phenyl ethyl bromide

75 = 7 i.e. rate of reaction with 2-phenylethyl bromide

7 timesthat
labelled 2-phenyl ethyl bromide
These observation show us that ß-carbon hydrogen bond is
brokenin therate

(4) Absence Of hydrogen exchange : Let us consider another

mechanism fu
dehydrohalogenation via the formation of carbanion.
Step 1 : The reaction involve abstraction of the proton by a base leavingbehindß
of electrons thus forming a carbanion.
Step 2 : Loss of halide to give the product alkene.
Step 3 : This is an acid base reaction, since the acidic protonis attached to
substrate is called a carbon acid and the carbanionis the comugate
carbon acid.
x x
(1) —c—c— + i
Base

Alkyl halide Carbanion

(Conjugate base)

(2)
Alkene
 10-9
Chemistry-I (PU) Elimination Reactions
aniC
org
mechanism (elimination, unimolecular. conjugatebase).
called El(cb)
•mis When a good carbanion stabilizing group is present on the
reaction.
El(cb) becomes favourable process for elimination.
I' Sæecular proton is lost,
by an El(cb) process.
uct occurs
f Jldolprod
OH
+ —9- CHECH
cH3

2-ButenaI
to stop at ß-hydroxy aldehyde stage because the carbonyl
is often difficult
also provides a driving force for the elimination product.
diecarbanionand
carbanions were formed in E2 mechanism the following experiment was
Tostudyif
2-phenylethyl bromide was reacted with a base sodium ethoxide in
lie substratewas
as a solvent. Consider that if carbanion were formed
labelledethanol which acted
regain hydrogen from the solvent before actually losing the halide ion to
ikene.Sincethe ethanol (solvent) used deuterium, the carbanion would be gaining a
and a proton

Radionwascarried out but interrupted in between and the unconsumped 2-phenylethyl

recovered. It showed no presence of deuterium.
This
showedthat E2 mechanism does not involve hydrogen exchange and thus showing
hrbanionare not formed

C6H,00 C6Hs00
C6Hs—CH—CH2
I C2HsOH I C2H50D
Carbanion
Labelled halide

C6H5CH=CH2 + Bro
Alkene
effect: The reaction shows
a large elemental effect. This effect was studied to
gatg»atyhich the halide In the
reactionthe reactivity
Of alkyl halides is as follows R-I > R-Br > R-CI > R.F.
• -react 40 to 60 times as fist
as the chlorides, alkyl iodides ga«
as bond
rate
 PharmaceuticalOrganic Chemistry - I (PO) 10-10

10.4.2 Orientation
Most of the E2 reactions follow Satyzeff's rule i.e. most branched
major product except
alkene and is formed as the for alkyl fluorides
alkcnc is the major product, it follows Hoffmann rule when a hydrogen theleast
and a
/ iodine are eliminated bonding electrons prevents the build up of negative
dtafiSAosing a proton giving¯fhetransitionstatekilkélie character and
But is a poor leaving group and when a base begins to
removea
alkyl fluoride, negative charge develops on the carbon that is losing
the proton
transition state a carbanion character.The carbanionsare stabilizedby
thelesser
alkyl groups that are bonded to a negatively charged carbon.
CHOO
CH3—CH— CH2CH2CH3 CH — CH2Cl-12CH3 + CH.CH
CH30H
(Major)

OCH3ö 6- OCH3 Carbamonlike

(Less stable) trans•
State (morestable)
Carbanionlike transitionstate H (Hoffmann
o
(Saytzeff Orientation)
CH. CH— CH — CH2CH3 CH2—CH

With larger bulky groups such as quaternary ammonium ion, the orientation IS
per Hoffmann rule because the bulky group causes a crowding in the transitionstate
less substituted carbon more accessible to the base for abstractionof proton.Alsothe
state has carbanion like character due to electron withdrawal by the positivelycharged
Thus the proton is lost from the carbon that can best accomodatethe positivecharge So
Hoffmann orientationthe least branchedalkene is the preferredproduct.
C2HsONa
eg. CH3CH2—CH2— +
C.H,OH
I - Pentene 2 - Pentene
2 - Pcntyl tnmcthyl (Major)
arnmomum Ion

eg. 1) CH3CH2—CH2CH—
3-bromo hexane 3 - hexene

alc.KOH
 Elminatiorl Reacoons
-l (PO) 10-11
Chemistry
aniC

of alkene
formation = CHR> RCH = CH2
of > = CH2
C CHR
r6ftß Antielimination Reaction
of E2 —
iStrY
e on the opposite side of the molecule the reaction is called
groups ar
rnunated
substituents must be in the same plane because sp orbital of
theeliminated
leaving groups become overlapping p orbital in the alkene. The
H and the
and in the same plane. Antielimination is
ifthe two bonds are parallel
occurs rapidly
<natlon and
- elrm
mination
attain anti-periplaner conformation of the departing groups.
moleculescannot
side of the molecule they are termed as syn-periplanar
are on the same
A iscalledsyn-elimination.
norbornyltosylate cannot achieve antiperiplanar structure due to its
between the ß-hydrogenand tosyl group is 1200.
thusthe dihedral angle
ng,ditv
to undergo sym-elimination. For anti-eliminatim the
theleavinggroups prefer
* shouldbe 1800
OTs
H
R07K*
D
D

Deuterated
norbomyl Syn product Anti product
tosylate (Major)
(Without Deuterium)
Factors
AffectingRate of E2 Reaction
Nature
of substrate :

increaseswith the presence of electm

theI-effectof - wighdra,ing group on the
these groups increase the acidity of
character
_Alsopresence of more the ß-H stabi Ing the
nurpber of alkyl or aryl groups increases the
on the carbon atom wherea
new double bond would be
Ofleaving
group :
the size of the
n therateofreaction. ability_pf increases and
 Orga ntc
PharrnaceuttcaI
El, E2 and El(cb) Reaction
10.6 Comparisonof
El(cb)
Onc step process Two step proccss
Tuo step process Second order
Second order kinetics kincqtcs
kinetics
First order 10
> 20 > 10
Reactivity order 30
increase rate Polar solvents decrease rate Non-hydroxyhc polar
Polar solvents increase the rate of
of reaction
of r:eaction
Transition state Carbanion formed
Carboéation is formed
Strong base required Strong base required
Solvent acts as a basc
the As temperature increases As temperature
As temperature increases increases the
i
the rate of reaction also rate of reaction also
rate of reaction also increase
increases

Non-stereospeclfic and Stereospecific and Non stereospecific and

nonstereoselective stereoselective nonstereoselcctive

Usually follows satyzeffs Follows Hoffmann's for Generally follows Hoffrnann•s

cationic or bulky groups. rule
rule
Follows Saytzeffs for
neutral and not very bulky

10.7 Comparison of Elimination and Nucleophilic SubstitutionReaction

Both elimination and nucleophilic substitution reactions require a substratemtha
leaving group and a base.
Sr. no. SN2 reaction E2 reaction
One step reaction One step reaction
2 Rate depends on concentration of Rate depends on concentration
substrate and nucleophile and substrate.
3 Reagent attacks the carbon to bring Reagent attacks the hydrogenfor
about substitution elimination
4 Reactivity 10 > 20 > 3 0 substrate 30 > 20 substrate
5 Inversion of configuration Usually trans elimination
6 Reagent acts as a nucleophile. Reagent acts as base
 EliminationReactions
(PU) 10-15
Chemistry-I
org E2 reaction
reaction
which may Requires a good base
nucleophile
a good
gcqUl base Favoured by high temperature and less
more polar
ture and polar solvent

solvent

Reactions
intermediate in the first step
tion as the
El
SNI
Follows first orderkinetic
first order kinetic
Follows Two step reaction
reaction
Twostep 3 0 > 2 0 > 10 carbocation
3 0 carbocation
Ructivity
the reagent on the Involvesattack on the hydrogen
attack
Involves of

Nonstereospecific
Solvent acts as a reagent
andweak base at low
Solvent
required
concentration
Lawtemperaturefavours the reaction High temperature favours the reaction

Summary

uyl Inlidesundergodehydrohalogenation in presence of a base to give an alkene. This

aehmination
typeof reaction.Elimination can be El and E2 type. El eliminationshowsfirst
kinetics,
whereasE2 eliminationfollows second order kinetics. "Ihe alkene is formed
Illtwo
steps(El) or in a single step (E2). The orientation is govemed by Satyzefs rule.
ceQuestion

El mechanism
is a
OrderOf step reaction.
reactivity Of alkyl halide
E2 in El is
reaction
4. follows
ce in rate of order kinetics.
reaction due difference in the isotope is called
5.
El reactio
n prefers
OfEl elimination.
reactionincreases
by using type of solvents.
intermediate is
fomed is El(cb) reactions.
 molecules where as
inductive effect diminishes over a short distance in
phenoxide ion delocalisation
of charges is responsible for its stabilisation. It is symbol
the letter M The mesomeric
effect is negative (-M) when the substituent is an
withdrawing group and the effect is positive (+M) when based on resonance
substituent is an electron releasing group and

• Examples of -M substituents: Nitro group, Acetyl group.

• Examples of +M substituents: Alcohols, Amines.
4.1.7 Steric Effect
[ University Exam.

\ The relative availability of pi electrons is affected by steric factors which can

overlapping of orbitals and thus affect the delocalization. For example N, N-dimcthylån
can easily undergo diazo coupling reaction but its 2, 6-dimethyl derivative prevents
reaction because these two methyl groups are ortho to the amino group. They prevent
overlap of p orbitals of nitrogen with the ring carbon and hence the transfer of
prevented which are necessary for the coupling reaction.

CHs CHs CH3 CH3 CH3 CH3 CH CH3

\../CHF

2,6-dimethyl
N,VimethyI aniline -N,N-dimethyl aniline

Steric effect is also seen by steric hindrance of bulky groups near the reaction site. TDB

affects the course of reaction or sometimes completely prevents the reactions to take plae
Esterification reactions are examples of reaction which are susceptible to steric hindrance.

4.2 Acids and Bases

The term acids and bases can be defined in many ways.
4.2.1 Arrhenius theory
This theory was derived by Svante Arrhenius. It described the acids as the substane
which produce hydrogen ions in solution whereas bases are substances which
hydroxide ions in solution.
Limitations: Ammonia reacts with hydrochloric acid to form ammonium chloride(0 1
but it does not produce hydroxide ions as per Arrhenius theory.
 Organic Chemistry-I (PW) 4-2 Factors

small differences in the numerical values Of the electronegativity. the most

method of calculation is that originally proposedby a
relative scale running from07 to 4 0,
table
Trends in electronegativity in a periodic
increases on passing from left to right
electronegativity
In general. along
group.
and decreases on descendinga
is undoubtedly the most electronegative of the elements
Hence. fluonnc
Tljere are some exceptions to this general rule Gall,
electronegative,
is the least than aluminium and silicon
electronegativities respectivclv
Germanium hasw•higher
the d- block contraction.
period immediately after the first row of the transition
Elcmcntsof the fourth
because the 3d-clcctrons are not effective at
unusuallysmallatomic radii
and smaller atomic size correlates with higher electron
increasednuclear charge,
is as follows
nus,thc electronegauvity trend

4.1.2 Resonance
[ University Exam.

When vwitinga Lewis structure, we restrict a molecule's electrons to certain

defined locations,either linking two atoms by a covalent bond or as unshared electrons@
single atom. Sometimes more than onc Lewis structure can be written for a molecule
reality,electronsdistributethemselves in the way that leads to their most stable
This sometimesmeans that a pair ofelectrons is delocalized, or shared by several nuclei
Resonancestructuresare then employed to approximate the true electronic
Take the example Of benzene shown below, in a Lewis diagram, two carbons
can
connected by one or two covalent bonds, but in the observed benzene molecule the
carbon bond lengths are (139 pm), longer than typical C=C double bonds (133 pm) yet
than typical C-C single bonds (154 pm).

c
Il
 equivalent. a fact no Lewis structure can explain.
Importantly,they are all
two Lewis structures canonical, contributing or resonating structures
More callsthe consideredto be their average, called a resonance
ocrcforc moleculeis hybrid. Hence
resentedin more than n structurge»'ere th structuresdiffer
andthe a moleculecan be
they are called resonance structures.
mentof electrons
arran
onl in in stabilitv egoance hybrid over the most stable of the (non-existent)
Thegain res is called the canonical Structure that is lower in
es a relativelv greater contribut10!! to the resonance hybrid. fact, resonance
energyandconsequentl' stability. increases with the number of canonical structures po"lble,
when these (non-existent) structures are equal in energyÅ
especially
resonance
Rules of
Resonance structuresof the same molecule are connected with a double-headed arrow.
to rememberthat the double-headed resonance arrow does not indicate a
It is important
the two Lewis structures interconvert.
processin which
2. All of the resonance structures must be proper Lewis structures, all the resonating
musthave same number of electrons if also unpaired, same net charge
structures
may vary.
althoughthe formal charges ezz-9
3. Wehaveto moveonly the position electrons in the different resonating structure, the
ofall nucleimustremain the same.
positions

Thisis a pair of resonance

These
arenotresonancestructures because the
hydrogens moved They are isomers.
4. Resonance sfructures of an individual molecule can
nonequivalent.
In the group of structures below, A either be equivalent or
equivalent
to the and B are equivalentbut C is not
other two structures.
:o: :ö: :ö:

H .00

c
 (PU) 4-6 Factors Affecting
Pharmaceutical Organic Chemistry-I Electron

:o: :ö:

ö—H
Resonance hybrid of acetic acid

:o:
CFL—C CHs—C

Resonance hybrid of acetate ion

2. Resonance is useful in understanding the bond length. When resonance takesplaq

compoundwith single and double bond then it changes the bond length such
decreases the single bond length and increases the double bond length. In a
manner "hen a resonance involves a double bond and @triple bond, the bond1
double bond decreases and for a triple bond it increases
3. Resonanceis used to explaili,dipqlc moment: •Pipole moment chan es with
betwrqn the two poles (directly proportional). Thus if resonance takes
larger area a higher dipole moment is developed and if resonance occurs overa
distance then it results in a loyvdipole moment.
4. Resonanceaffects acidity and basicity:[If the Ione pair of electrons on a
Unvolved in resonancethen they are less available for donation and hence the co
will show low basici!YJ
of acids if the apion is stabiliscd by resonance then the acid must have
given up proton and acts as a strong acido
e.g. is a weak base due to delocalisation Of Ione pair of electrons
nitrogen and hence less available to be donated.

CHs—C CHs — C = NH,

2

Acetamide resonating structures

Phenolate ion is resonance stabilised and therefore does not donate electron rea
b
hence acting as a weak base or we can say that the acid (Phenol) is strong.
 :ö:

H20

Phenolate ion
Phenol
Resonating structures of phenol

:OH
:öH
e:

Less stable structures due to charge separation

Resonating structures ofphenolate ion

More stable structure

4.1.3 Hyperconjugation [ University Exam. : 2009, 2010 ]

Hyperconjugation occurs when an H—Cbond is attached to an

such
as doublebondor a benzene@gg; the sigma (G) electrons of the H—Cbond interact or enter
with the unsaturated system. •rhe concept of hyperconjugation was developed
intoconjugation
byBakerandNathanand is also known as Baker and Nathan effect
Compoundshould have at least one sp2-hvbrid carbon of either alkene alkyl carbocation
or alkylfree
to sp2 hybrid.carbon should have at least one
hydrogeyIf boththese conditions are
fulfilled then hyperconjugation will take place in the
molecule

Ethylradicalis a hybrid of
not structure I but also other 3 structures in which a double
bondjoinsthetwo
carbons and an odd electron is held by a hydrogen atom.