Mechanism of

Organic Reactions

S D Samant
Institute of Chemical Technology, Mumbai

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 To understand organic chemistry it is necessary to know:

What occurs in a reaction?

Why and how chemical reaction takes place?
How a reaction can be described?

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Formation of molecule

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 ATOM Nucleus (p+n)

Electrons Kernel electrons

A

Electronic configuration (shells , orbital)

ATOMIC ORBITALS (AO) (outermost)

Overlap of Aos Hybridization

Overlap
B
Molecular orbitals
(Mos)
Bond formation (ionic , covalent , coordinate )

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 MOLECULE

3D structure stereochemistry Electronic structures

(i) Polarization effect I C
(inductive effect)
(ii) polarizability effect
(electromeric effect )
(iii) Resonance

MOLECULE + MOLECULE

Bond breaking Concentrated reactions

(pericyclic reactions)

Homolytic Heterolytic D

Radicals Cations Anions other species

REACTION MECHANISM
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 Atoms Molecule

Nuclei Framework

Electrons Orbitals

3D Structure Configurations, conformations,

isomerism ..

Prerequisite: Electronic configuration

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 MOLECULE

3D Structure Electronic structure

Reactivity

Reaction

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 Atomic structure
versus
Molecular structure

AO vs MO

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n A.O.s n M.O.s
(s,p,d,f )

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 Approximations

Linear combination of atomic orbitals

Consider only the valence orbitals

Consider only that part of your interest

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 Electronic Structure

Qualitative description of M. O. s of simple acyclic and monoclinic system

(a) Molecular Orbital Energy Diagrams (MOED)
- Explanation of reactivity
(b) Molecular Orbital energies
(c) Orbital overlap
(d) Coefficient of A.O.s in M.Os
(e) Frontier Molecular Orbitals (FMOs)

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How is a CHEMICAL BOND formed?

Ionic bond

Covalent bond

Coordinate bond

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Hybridization

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 FMO
LUMO (acceptor orbital ) Nu

-------------------
HOMO (donor orbital) E

Important orbital

Electrophile LUMO Nucleophile HOMO

Acid (lewis) LUMO Base (lewis ) HOMO

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FMOs in :

Electrophilicity & Basicity

Acidity & Basicity (HSAB)

Simple reactions

Pericyclic reactions

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ORGANIC REACTION MECHANISM
Desired reaction :
Reactant T, Catalyst, solvent Product

product By product Kinetic Stereochemistry

spread

Reaction Mechanism

TESTING

Stereochem kinetic trap. Isotropic Solvent Substrate

intermediate studies effect effect

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 Mechanism
confirmed

1) explanation of other reaction

2) further development
3) predictions

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Important Symbols describing
Reaction Mechnaism

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Irreversible reaction to product
Reaction which does not processd
Forward & Backward reaction
Reaction with more than one step
Reversible reaction
Reversible reaction ; Equilibrium favours products

Reversible reaction ; Equilibrium favours

reactant

Reaction with inversion of cofiguration

Indication of resonance

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Direction of
migration

Migration Migration Half headed

origin terminus arrow
shift of 2e- 1 e- shift

Curly Arrow

Use appropriate symbols

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 Indicating Steps in Mechanisms

Curved arrows indicate breaking and forming of

bonds

Arrowhead with a half head (fish-hook)

indicates homolytic and homogenic steps (called
radical processes)

Arrowhead with a complete head indicates

heterolytic and heterogenic steps (called polar
processes)

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 Using Curved Arrows in Polar Reaction Mechanisms

Curved arrows are a way to keep track of changes in bonding in

polar reaction
The arrows track electron movement
Electrons always move in pairs
Charges change during the reaction
One curved arrow corresponds to one step in a reaction mechanism
The arrow goes from the nucleophilic reaction site to the
electrophilic reaction site

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 Rules for Using Curved Arrows

The nucleophilic site can be neutral or negatively charged

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 The electrophilic site can be neutral or positively charged

Dont exceed the octet rule (or duet)

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 Examination of a molecule
with respect to its electronic
structure

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 Formal charge

Formal charge =
Valence electrons (1/2 bonding e- s + All lone pair e-s)

= Valence e- s (lines + dots )

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Polarization effect Inductive effect

Polarizability effect Electromeric effect

Localized and Delocalized bonds

Resonance and related phenomena

27
 Polarizability

The ability of the surroundings (solvent or other polar molecules) to

make a molecules polar. It is like making something magnetic by
pass a magnet over it.

It starts out neutral but when the right atom or molecule comes close
it becomes partial positive or partial negative.

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 Polarization - change in electron distribution as a response to change in
electronic nature of the surroundings
Polarizability is the tendency to undergo polarization
Polar reactions occur between regions of high electron density and regions
of low electron density

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 Resonance

A way to indicate delocalization of electron

Localized vs Delocalized Bonds

Unique Structure vs Resonance structures

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 Resonance Structures

Hypothetical BUT Useful

Hypothetical means taken to explain REAL

object

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Drawing of resonance structures

Nuclei do not move Geometry of the molecule does not change

Electrons move

Follow standard rules of valence

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 Each resonance structure
contributes to some extent to
the actual structure of the
molecule

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 Why do Organic
Reactions Happen?

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Energy change = Coulombic interaction + Orbital interaction

Orbital interaction = FMO interaction + Other interactions

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 How do the organic reactions occur: Mechanism

In an organic reaction, we see the transformation that has occurred. The

mechanism describes the steps behind the changes that we can observe

Reactions occur in defined steps that lead from reactant to product

36
 Steps in Mechanisms

A step involves either the formation or breaking of a covalent bond

Steps can occur in individually or in combination with other steps

When several steps occur at the same time they are said to be
concerted

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Understanding unit steps

Acid Base concept

Nucleophile and Electrophile

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 Energy Frofile Diagram

schematic representation of the energy changes that take place as reactants

are converted to products.
plots the energy on the y axis versus the progress of reaction, often labeled
as the reaction coordinate, on the x axis.

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 For the general reaction:

The energy diagram would be shown as:

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 Consider the following two step reaction:

An energy diagram must be drawn for each step.

The two energy diagrams must then be combined to form an energy
diagram for the overall two-step reaction.
Each step has its own energy barrier, with a transition state at the energy
maximum.
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48
 Figure 6.6
Complete energy diagram for
the two-step conversion of

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Ea is the energy barrier that must be exceeded for reactants to be
converted to products.

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 Describing a Reaction: Intermediates

If a reaction occurs in more than one step, it must involve species that
are neither the reactant nor the final product

These are called reaction intermediates or simply intermediates

Each step has its own free energy of activation

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Acids and Bases

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An electrophile
is electron-loving
is an electron-poor species
can form a bond by accepting a pair of electrons
may be either neutral or positively charged
is a Lewis acid

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A nucleophile
is nucleus-loving
is an electron-rich species
can form a bond by donating a pair of electrons
may be either neutral or negatively charged
is a Lewis base

56
Generalized Polar Reactions

An electrophile, an electron-poor species, combines with a

nucleophile, an electron-rich species

The combination is indicated with a curved arrow from

nucleophile to electrophile

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 Ambident Nucleophiles

O N O O N O (NO2)

O N O (NO2)
O N O

H2 C C O H2 C C O (enolate)

o o o
o o

(phenolate ion)

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 Some species can act as an electrophile or a nucleophile
depending on the circumstances

Example Water acts as a nucleophile when it donates a

pair of electrons, and acts as an electrophile
when it donates H+

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 Bond Breaking
in anticipation of better bonds

HOW and What it Results into

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 Types of Steps in Reaction Mechanisms

Bond formation or breakage can be symmetrical or unsymetrical

Symmetrical - homolytic
Unsymmetrical - heterolytic

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 General C-X Bond Breaking processes

C X
C X

Carbenium ion

C X C X C X
Carbanion

C X C X
Radical

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 C X C X X Leaving group

Self dissociation

OR

C X + Z C XZ C XZ
assisted dissociation

Y C C Y C C

Addition

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Intermediates

What are they?

Transition State and Intermediates
How are they formed?
How do they look like?
Are they stable?
What are their typical reactions?

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Structures

Carbocation: Trivalent, Planar, Trigonal

Carbanion: Trivalent, Tetrahedral

Carbon radical: Tetrahedral or Trigonal

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General principles of stability:

Increase charge Unstable

Decrease charge Stable

Localise charge Unstable

Disperse, delocalise change Stable

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 RADICAL REACTION
A] Propagation processes :
1) Abstraction . .
R + HC RH + C
2) Addition . .
R + C=C RCC

3) Decompostion .
RC=O R + O= C=O
.O
. .. .
R + Mol R + Mol
. ..
R Mol + R
B] Termination process :
1) Combination : . .
R + R RR
2) Disproportion : . . ..
R Mol + Mol

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C] Rearrangements : Not common

Characteristics

* Susceptible to radicals
* Chain mechanisms
* Conc. Of radicals is low
- Termination processes less frequent
- termination process have negligible E act
* Susceptible to inhibitors
* Ionic mechanism may compete.

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 General Reaction of Free Radicals
Propagation processes Termination processes

Abstraction Addition Disproportionation Combination

reaction reaction reaction reaction
. . . . . .
X + H-C X + C=C R+ R R+ R
. . . ..
X-H + C XCC R + R RR
. . . . . .
Cl + HC Br + C=C CH3-CH2 + CH2-CH3 Cl + Cl
. .
HCl + C BrCC CH3CH3 + CH2 =CH2 ClCl

70
 Radical Reactions

Not as common as polar reactions

Radicals react to complete electron octet of valence
shell
A radical can break a bond in another molecule and
abstract a partner with an electron, giving substitution
in the original molecule
A radical can add to an alkene to give a new radical,
causing an addition reaction

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 Steps in Radical Substitution

Three types of steps

Initiation homolytic formation of two reactive species with
unpaired electrons
Example formation of Cl atoms form Cl2 and light
Propagation reaction with molecule to generate radical
Example - reaction of chlorine atom with methane
to give HCl and CH3.

Termination combination of two radicals to form a stable

product: CH3. + CH3. CH3CH3
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 Photohalogenation of alkanes (H in kJ/mol) )

Steps F Cl Br I

. .
X X X + X +150.6 +242.7 +188.3 +150.6

. .
X + CH4 CH3 + HX -146.4 -12.55 +50.21 +117.2

. .
CH3 + X2 H3C X +X -334.7 -83.68 -96.23 -62.76

Overall -481.1 -96.23 -46.23 +54.44

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Act. E : . .
Cl + CH4 CH3 + HCl 16.11 Kj

. .
CH3 + Cl2 CH3Cl + Cl < 21 kj

Alternative mechanism :
. .
Cl + CH4 H3C-- Cl +H
. .
H + Cl2 HCl + Cl

Both steps endothermic (only at High T )

Act . E : . .
Br + CH4 CH3 + HBr (74.48 kj)

HCH3 HCH2CH3 HCHMe2 HCMe3

CH Bond
E (kcal/mol) 102 96 92 89

(77)
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 Radical addition to (C=C)

R + HX R H + X

+ HX
X bond
Radicals always attack less substituted (terminal) carbon atom of a double

H
+ HX X
X X

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 X in HX F Cl Br I
(Kcal/mol)

-45 -26 -5 +7

+37 +5 -11 -27

Radical mechanism effectively competes with ionic mechanism in the case

of HBr

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 General Reaction of Carbenion Ion
Nucleophilic Elimination Rearrangement Additon to
attack of H+ from (common) C=C
C+ + : Nu position less stable (C+ ) C+ + C=C
H
C Nu C C+ more stable (C+ ) CCC+

C=C Wagner
olefins Meerwein
SN 1 (II)
AE1 (II) E1
(A) (B) (C) (D)

A or B A or B D
(polymn)

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 CARBOCATION

Carbonium ion Carbenium ion

C+, C - pentavalent C+, C - trivalent ,
CH5+ CH3+

Carbonium ion (onium) Carb-enium ion (enium)

Carbanion

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 Self Dissociation:
K1
R-Cl R+Cl - ionization

Tight ion pair

Solvent, K2 + :: -
+ - R
R Cl : : Cl
Solvent separated ion pair
K3
+:: -
R : : Cl R+ + Cl - dissociation
ions

* Stereochemical outcome:
Nu Nu
Nu-R R+ 80
R-Nu
 PROTONATION PROCESSES
1. Protonation of alchols :

H
k1 R O protonium ion
R OH + H
H
k2 R OH2
R OH 2

k3
R OH2 R + H2O dissociation

2. Protonation of ethers :

+
k1
R O R +H R O R
H
+ +
k2 R HO R
R O R
H
+ +
R HO R R + HO R
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 3. Protonation of a carbonyl group :

R R
C O + H C OH

R R

R R
C OH C OH
R R

4. Protonation of mercaptans & sulphides :

R SH + H R S R

R S R + H R S R

H
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 5. Protonation of an olefin :

R C C R1 + H R C C R1
H H

H H H

H H2 H2 H
R C C R1 R C C R1 + R C C R1

H H

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 An Example of a Polar Reaction: Addition of HBr to Ethylene

HBr adds to the part of C-C double bond

The bond is electron-rich, allowing it to function as a nucleophile
H-Br is electron deficient at the H since Br is much more
electronegative, making HBr an electrophile

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 First Step in Addition

In the addition of HBr the

(conceptual) transition-state
structure for the first step
The bond between carbons
begins to break
The CH bond begins to
form
The HBr bond begins to
break

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* With Acid halide:
O +O: AlCl3 -
.. AlCl3 ..
R Cl : + R Cl:
.. ..

+O: AlCl3 - +O: AlCl3 -

R Cl: R Cl:

* With Acid anhydride:

+
O O O :O-AlCl3 -
+ AlCl3
R O R R O R
..
+ O O : -AlCl3
O :O-AlCl3- +
R O R
R O R

..
O O : -AlCl3
+ 86
R O R
+
 Complexation of alkyl halide with a Lewis acid
+
.. -
.. K1
R-Cl : + AlCl3 R-Cl-AlCl3
.. ..
Complex

+ -
.. K2
R-Cl-AlCl3 R+(AlCl4)-
.. tight ion pair

K3 , solvent
R+(AlCl4)- R+ (AlCl4)-

Solvent separted ion pair

K4
- R+ + (AlCl4)-
R+ (AlCl4)
ions (dissociation)

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 General Raction of Carbanion

Protonation Attack at e Elimination Rearrangement

C: - + H deficient carbon of nucleofuge (rare)
from position
CH

sp3 carbon sp2 carbon

C- alkylation

At C=C At C=O
polymerisation Tetrahedral mechanism
(Anionic) (Aldol type reaction)

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 T etrahedral Mechanism:
O O
+
-
Cl ?
+ -OH
R Cl R OH

(SN 2 type)

(a) O O-
+ -
R X Nu R Nu
X SP 3

tetrahedral
-
O O
SP2
R Nu R Nu
X
Planar
Substitution
Nu= -OH, H 2O, NH3 , R-NH2

OR X= Cl, OH, OCOR, NH2

O- OH
+ H+
R Nu R Nu
X X

X= H, akyl , NH 2
Addition
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 ELECTRON BOOK KEEPING
Homogenic bond f ormations

(1) CH3 + CH3 CH3-CH3

(2) CH3-CH2 + Cl CH3-CH2-Cl

Heterogenic bond f ormations

(3) CH3 + OH CH3-OH

(4) (C2H5)3N + H (C2H5)3NH

(5) (CH3)3N + O (CH3)3N-O 90

 Heterogenic bond f ormations

H
(1) CH3-O-CH3 + H CH3-O-CH3

(2) CH3-O-N=O + O CH3-O-N=O

O

(3) CH3-CH2-Cl + AlCl3 CH3-CH2-Cl-AlCl3

(4) C=O + H H-C=O

(5) X-CH2-H + OH X-CH2 + H-O-H

91