M.Sc.

Industrial Chemistry
Semester I
Organic Chemistry I
IC-503

Topics- Types of Reaction mechanism

Methods of determining Reaction Mechanism
Types of Reaction mechanism

A reaction mechanism is the actual process by which a reaction takes place. It explains which
bonds are broken, in what order, how many steps are involved, the relative rate of each step
etc.

• The reaction mechanism describes the sequence of elementary reactions that must
occur to go from reactants to products.
• Reaction intermediates are formed in one step and then consumed in a later step of
the reaction mechanism.

Types of mechanism

Depending on how the bonds break, organic mechanisms can be divided into three basic types.

a. Homolytic or free radical mechanism :

If a bond breaks in such a way that each fragment gets one electron , free radicals are formed
and such reactions are said to take place by hemolytic or free radical mechanism.

They are composed of three key phases: initiation, termination, and propagation.

Step Where There Is a Net Increase In The Number Of Free Radicals Is Called,
“Initiation”

Free-radical reactions generally require heat or light to be applied. That’s because either of
these energy sources can lead to homolytic cleavage of relatively weak bonds like Cl-Cl to
give free radicals [i.e. Cl• ]
Every free radical reaction begins with a step where free radicals are created, and for that
reason this initial step is called initiation.

Step Where There Is No Net Gain Or Loss Of Free Radicals Is Called “Propagation”

Chlorine radicals are highly reactive, and can combine with a hydrogen from methane to give
the methyl radical, •CH3

there’s one free radical in the reactants and one in the products. So there is no net increase in
the number of free radicals.
This type of step is referred to as “propagation”.

There Are Two Propagation Steps In Free-Radical Substitution

Take the methyl radical, and it reacts with the Cl2 still present. This gives us CH3Cl and the
chlorine radical. Note that there has been no net change in the number of free radicals, so this
is still a “propagation”.
Again that we are forming a chlorine radical. This chlorine radical can then perform
Propagation Step #1 on a new molecule of our substrate (CH4), continuing the process. It’s
achain reaction – once generated, chlorine radical is catalytic. That’s why we only need a
small amount of chlorine radical for this reaction to proceed.

Step Where There Is A Net Decrease In Free Radicals Is Called, “Termination”

If the concentration of Cl2 is low relative to CH4 (in other words, Cl2 is our limiting reagent)
then the rate of Propagation Step #2 will slow down as its concentration decreases. Without
any Cl2 to react with, our •CH3 radicals can just combine with another free radical (such as •Cl)
to give CH3Cl, for example. There is essentially no barrier to this reaction. Note that here the
number of free radicals decreases from 2 to zero. This is called termination.

It’s also possible for two methyl groups to combine together to give CH 3–CH3 ; this is also
termination!
If we have multiple equivalents (excess) of Cl2 in the presence of CH3Cl.

An atom of Cl• could react with CH3Cl to give •CH2Cl [and HCl], which could then react
with Cl2 to give CH2Cl2

Likewise, if we still have an excess of Cl2, then we will observe conversion of CH2Cl2 to
CHCl3.

Finally, given enough Cl2 we could then imagine the conversion of CHCl3 to give CCl4.

At this point there are no further C-H bonds to react with the chlorine radical, and thus our
reaction would eventually terminate.

The bottom line here is that alkanes, given a large enough (excess) of Cl2, will eventually
have all of their hydrogens replaced with chlorine.

This pathway is in fact how dichloromethane (CH2Cl2 – a common laboratory solvent)

chloroform (CHCl3) and carbon tetrachloride (CCl4) are produced industrially. For many
decades, CCl4 was produced on mega-ton scale for use as a refrigerant and dry cleaning
solvent
b. Heterolytic mechanism :
If a bond breaks in such a way that both bonding electrons remain with one fragment, ions are
formed and such reactions are said to take place by heterolytic mechanism.

(Discussed in detail in carbocation notes)

c.Pericyclic Mechanism

This mechanism involves the cyclic movements of the electrons in the bond breaking and bond
making. There are no intermediates, ions or free radicals. Reactions with this type of
mechanism are called pericyclic mechanism.

Pericyclic reactions are a unique set of reactions that takes place through a cyclic transition state in a
concerted fashion and exhibit high levels of stereospecificity. Additionally, for pericyclic reactions no
intermediates have been isolated and the reactions are free from changes in solvent polarity, free radical
generators and even catalysts. All these reactions are potentially reversible in nature.

Unlike ionic reactions, for pericyclic reactions there is no definite sense of direction to the movement
of electrons as the electrons move in a cyclic manner. There is also a difference between a synchronous
reaction and a multi-stage concerted process as in synchronous reaction all bond-making and bond-
breaking events take place simultaneously, but in a multi-stage concerted process some events precede
others without producing an intermediate state. Most of the pericyclic reactions are concerted and may
or may not be synchronous.

Though some of the pericyclic reactions occur spontaneously, but in major of them introduction of
energy either in the form of heat or light is required. Moreover product depends on the source of energy
used.

All pericyclic reactions share common features discussed above. They are classified into following four
categories

1 Electrocyclic reactions
2 Cycloaddition
3 Sigmatropic rearrangements
1. Electrocyclic reactions
Electrocyclic reactions are characterized by the creation of a ring from an open chain conjugated system,
with a σ bond forming across the ends of the conjugated system or opening of a cyclic system under
ring strain to give rise to a diene. Electrocyclic reactions are unimolecular in nature.

Most of the electrocyclic reactions are ring closing and a few are ring opening in conformationally
strained systems such as cyclobutene. Electrocyclic ring closing reactions have been observed for
cationic and anionic polyene species such as allyl cations as well.

If we look at the stereochemistry of electrocyclic reactions, in the following reaction one stereoisomer
gave rise to one specific product only.

The stereospecificity of electrocyclic reaction can be explained based on Frontier molecular orbital
(FMO) theory, especially considering the HOMO of the triene, the mode of bond rotation decides
stereochemistry of product formed.
There are two known modes of bond rotation namely conrotation and disrotation as shown below.

If we consider termini of the HOMO of the triene system, it can be seen that the end groups
must rotate in a disrotatory manner (twist in opposite directions, when observed front-on) to
form the bond. On the other hand, when photoactivated, an electron moves from the HOMO
of triene to the next orbital, the LUMO (now this orbital contains an electron and it is no longer
unoccupied). In this photo excited system ring will close in the opposite direction as compared
to the thermal system and moreover the groups will conrotate i.e., they will twist in the same
way to form the sigma bond.

As electrocyclic reactions are reversible, whether ring opening/closing will take place is
determined by thermodynamics. However, the stereochemistry of product formed is not
influenced by the thermodynamic stability rules.

In another example, thermal ring opening reaction of 3,4-dimethylcyclobutene (which may

exist as cis and trans isomers) gives hexadiene (which may be cis, cis/ cis, trans/ trans, trans
isomers). In the reaction, cis 3,4-dimethylcyclobutene on ring opening gave only cis, trans
product, while trans 3,4-dimethylcyclobutene isomer, leads to formation of trans-trans diene.

These reactions take place via conrotatory motion about the C3-C4 bond in a four-member
cyclic transition state.

2. Cycloaddition Reactions

A cycloaddition is a reaction that simultaneously shapes at least 2 new bonds, and in doing so,
converts two or more open-chain molecules into rings. The evolution state for such reactions
characteristically engages the electrons of the molecules moving in continuous rings, making
it a pericyclic reaction. A concerted amalgamation of two π-electron systems to form a ring of
atoms having two new σ bonds and 2 fewer π bonds is said a cycloaddition reaction. The
number of participating π- electrons in each component is specified in brackets preceding the
name, and the reorganization of electrons might be illustrated via a cycle of curved arrows -
each representing the movement of a pair of electrons. Ring-opening process is cyclo-
reversion.
These reactions involve concerted combination of two π-electron systems to form a ring
system. Cycloaddition reactions are described as [i+j] additions, when a system of “i”
conjugated atoms combines with a structure consisting of “j” conjugated atoms. In
cycloaddition reactions carbon–carbon bond formation takes place without any use of a
nucleophile or electrophile. Among the pericyclic reactions, cycloadditions are most abundant
and useful set of reactions.

The most general cycloaddition reaction is the [4π+2π] cyclization recognized as the Diels-
Alder reaction. In Diels-Alder terminology the two reactants are termed to as the diene and the
dienophile. The subsequent diagram illustrates instances of [4π+2π], a light induced [2π+2π]
and [6π+4π] cycloadditions.

Cycloaddition reactions include the formation of a cyclic product due to addition of 2 different
π bond enclosing components, which are connected via newly formed two σ bonds at their ends
at the expense of two π bonds. It is generally reversible and the backward reaction is as well
termed to as retro-cycloaddition or a cycloreversion. The classic instance of cycloaddition is
Diels-Alder reaction between a Diene and a Dienophile to provide a cyclic adduct.
Cycloaddition, and the reverse procedure retrocycloaddion, can be examined in the reaction
between 1, 3-butadiene and ethene to provide cyclohexene.

The 1, 3-butadiene is a conjugated π-system through 4 π-electrons and the ethene is a

conjugated π-system by 2 π-electrons. The reaction between 1, 3-butadiene and ethene to
provide cyclohexene is explained as a [4+2] cycloaddition reaction. This kind of cycloaddition
is as well said a Diels-Alder reaction. In a Diels-Alder reaction the 4 π-electron system is
termed to as "the diene" and the 2 π-electron system as the 'dieneophile'. Such terms are utilized
in related [4+2] reaction systems even when the functional groups aren't actually dienes or
alkenes.

The formation of the Diels-Alder adduct is an exothermic reaction. It follows that elevated
temperatures favour retrocycloaddition and low temperatures favour adducts formation.
Though, many cycloaddition reactions need moderate heating to conquer the activation energy.
So a cycloaddition may require heating to make the reaction "go", but if it is heated too much
the equilibrium will favour retrocycloaddition. The compound cyclopentadiene slowly
undergoes cycloaddition with itself: one molecule of cyclopentadiene acts as a 4 π-electron
diene and the other as a 2 π-electron dieneophile. The product is a Diels-Alder 'adduct',
frequently said dicyclopentadiene. This dimeric substance can be cracked back to
cyclopentadiene via heating at 150°C for an hour and then distilling off the diene monomer.

Diels-Alder cycloaddition reactions proceed more professionally if the diene is electron rich
and the dienophile is electron poor. Cyclopentadiene is electron wealthy. The method to build
the dieneophile electron pitiable is to add electron withdrawing groups, these as carbonyl
functions. Maleic anhydride is an electron poor dieneophile which reacts by cyclopentadiene
to provide an endo Diels-Alder adduct. Upon heating at 190°C, the endo conformation adduct
accepts the more stable exo-adduct conformation.

1-Methoxy-1,3-butadiene reacts through acrylonitrile to provide 3-methoxy-4-

cyanocyclohexene rather than the 3-methoxy-5-cyanocyclohexene isomer. This "ortho"
regioselectivity of this reaction can be rationalised using FMO theory.

3. Sigmatropic Rearrangements

Molecular rearrangements in which a σ-bonded atom or group, flanked by one or more π-

electron systems, shifts to a new location with a corresponding reorganization of the π-bonds
are called sigmatropic reactions. The total number of σ-bonds and π-bonds remain unchanged.
These rearrangements are described by two numbers set in brackets, which refer to the relative
distance (in atoms) each end of the σ-bond has moved, as illustrated by the first equation in the
diagram below. The most common atom to undergo sigmatropic shifts is hydrogen or one of
its isotopes. The second equation in the diagram shows a facile [1,5] hydrogen shift which
converts a relatively unstable allene system into a conjugated triene. Note that this
rearrangement, which involves the relocation of three pairs of bonding electrons, may be
described by three curved arrows.

The [3,3] sigmatropic rearrangement of 1,5-dienes or allyl vinyl ethers, known respectively as
the Cope and Claisen rearrangements, are among the most commonly used sigmatropic
reactions. Three examples of the Cope rearrangement are shown in the following diagram.
Reactions 1 and 2 (top row) demonstrate the stereospecificity of this reaction. The light blue
σ-bond joins two allyl groups, oriented so their ends are near each other. Since each allyl
segment is the locus of a [1,3] shift, the overall reaction is classified as a [3,3] rearrangement.
The three pink colored curved arrows describe the redistribution of three bonding electron pairs
in the course of this reversible rearrangement.
The diene reactant in the reaction 3 is drawn in an extended conformation. This molecule must
assume a coiled conformation (as above) before the [3,3] rearrangement can take place. The
product of this rearrangement is an enol which immediately tautomerizes to its keto form. Such
variants are termed the oxy-Cope rearrangement, and are useful because the reverse
rearrangement is blocked by rapid ketonization. If the hydroxyl substituent is converted to an
alkoxide salt, the activation energy of the rearrangement is lowered significantly.

Reaction 4. is the classic rearrangement of an allyl phenyl ether to an ortho-allyl phenol. The
methyl substituent on the allyl moiety serves to demonstrate the bonding shift at that site. The
initial cyclohexadienone product immediately tautomerizes to a phenol, regaining the stability
of the aromatic ring.
Reaction 5 is an aliphatic analog in which a vinyl group replaces the aromatic ring. In both
cases three pairs of bonding electrons undergo a reorganization.

The allylic sulfoxide in reaction 6 rearranges reversibly to a less stable sulfenate ester. The
weak S-O bond may be reductively cleaved by trimethyl phosphite to an allylic alcohol and a
thiol (not shown).
Reaction 7 shows a similar rearrangement of a sulfur ylide to a cyclic sulfide. The [2,3]-Wittig
rearrangement is yet another example.
Methods of determining Reaction Mechanism
There are a number of commonly used methods for determining reaction mechanism. In most
cases, one method is not sufficient. Reaction intermediates are the important class of chemical
species, which are quite helpful in understanding the mechanism of a chemical reaction.

1. Isolation of intermediate :
Isolation of intermediates gives the valuable information to identify the exact mechanism. It is
sometimes possible to isolate an intermediate from a reaction mixture by stopping the reaction
after a short time or by the use of very mild conditions. For example, Hoffmann’s bromamide
reaction:

During this reaction following intermediates were formed and isolated:

In order to explain the formation of these intermediates, following mechanism was proposed:

2. Detection of intermediate :
In many cases, intermediate cannot be isolated but can be detected. It can be detected by IR,
NMR or other spectroscopic technique. The detection of Raman spectra of NO2+ (nitronium
ion) indicates it is an intermediate in nitration of benzene. Hence, nitration of benzene is
electrophilic substitution reaction and the following mechanism for the nitration of benzene
was proposed:
3. Stereochemical evidence :
If the products of a reaction are capable of existing in more than one stereoisomeric forms, the
form which is obtained may give information about the mechanism. For example, in
SN2 reaction the product product obtained is always inverted. This is only possible if the attack
of nucleophile and removal of leaving group takes place simultaneously. In such cases,
nucleophile attacks from backside of leaving group to give inverted product.
4. Identification of products :
Identification of the products of a reaction also helps to define the reaction mechanism.

For example, elimination reaction of 2-bromobutane.

From the identification of but-2-ene as major product and bu-1-ene as minor product, following
mechanism can be proposed:

5. Isotope labeling ( Tracer technique) :

When one isotope of the bonded atom is replaced by its heavier isotope, the rate of bond
breaking becomes slower. So by comparing the rate of original bond breaking with that of the
heavier isotope substituted bond, we can determine whether a particular bond breaks in the rate
determining step or not. The effect of heavier isotope on the rate of the bond breaking is called
isotope effect.

Much important information can be obtained by using molecules that have isotopically labeled
and tracing the path of the reaction in that way.

For example, ester undergoes hydrolysis to form a mixture of carboxylic acid and alcohol.
The products may have been formed by acyl-oxygen bond fission (a) or by alkyl-oxygen bond
fission (b). If the hydrolysis of ester is carried out using H 2O18 (i.e. oxygen having mass 18),
the following products would be expected:

In this reaction, the appearance of O18 in carboxylic acid has been confirmed by mass
spectroscopy. So the fission must have occurred at acyl-oxygen bond in the hydrolysis of ester.

6. Trapping of intermediate :
In some cases, the suspected intermediate is known to be one that reacts in a given way with a
certain compound. The intermediate can then be trapped by running the reaction in the presence
of that compound.

For example, benzyne reacts with dienes in Diels- Alder reaction. In any reaction where a
benzyne is suspected intermediate, the addition of a diene and the detection of Diels-Alder
addition product indicates that the benzyne was present.

The action of p-chlorotoluene with sodamide in presence of liquid ammonia yields a mixture
of para and meta toluidene. using the method of trapping intermediate, predict the suitable
mechanism for the following reaction:

The

mechanism of this reaction is believed to proceed as follows by trapping benzyne intermediate.

Step – I : The first step involves the loss of H+ and Cl- from p-chlorotoluene to form a benzyne
intermediate.

Step – II : The second step involves the attack of the benzyne intermediate by NH2– followed
by protonation.