Mechanism of Organic Reactions

Cleavage of covalent bond:

I) Homolytic cleavage (homolysis): The symmetrical fission or cleavage of a covalent

bond between two atoms or groups in such a way that each atom or group acquires one

electron from the bonding electron pair is called as hemolytic fission or homolysis.

An atom or group of atoms possessing an unpaired electron is called as free radical.

Free radicals are neutral and highly reactive species. Hemolytic fission generally takes

place in vapour phase or in the presence of non polar solvent like CCl4, and is catalyzed

by sunlight.

II) Heterolytic cleavage (Heterolysis): The unsymmetrical fission or cleavage of a

covalent bond between two atoms or groups in such a way that shared bonding electron

pair retains with more electronegative atom, is called as Heterolytic fission or heterolysis.

It is favoured in polar solvent and gives rise to ionic species. Heterolysis may be

presented as follows.

An organic species containing positively charged and triply bonded carbon atom

which is formed by heterolytic cleavage, is called as carbocation or carbonium ion. The

carbon loses both the shared bonding electrons and gets +ve charge with six electrons.

e.g.

An organic species containing negatively charged and triply bonded carbon atoms

which is formed by heterolytic fission, is called as carbanion. In this cleavage, carbon

retains both the shared bonding electrons to get negative charge.

Types of organic reagents:

I) Electrophilic reagents (Electrophiles): Positively charged species like H+, NO2+,

NO+ or electron deficient neutral molecules (Lewis acids like AlCl3, BF3 are called as

Electrophiles. They attack negatively charged electron rich species.

II) Nucleophilic reagents (Nucleophiles): Negatively charged species like OH¯, CN¯,

OR¯, RCOO¯ etc or neutral electron rich molecules (Lewis bases) like R-O-R, R-OH, R-

NH2 etc are called as Nucleophiles. They can offer a pair of electrons for bond formation

with another electron deficient molecule.

Types of organic reactions:

Organic reactions may be broadly classified into following types.

a) Substitution or Displacement reactions: when an atom or group of atoms is

replaced by another atom or group, the reaction is called as substitution or displacement

reaction.

There are two types of substitution reaction.

1. Electrophilic substitution reaction: In Electrophilic substitution reaction, atom or

group attached to carbon atom of an organic compound is substituted by electrophile.

2. Nucleophilic substitution reaction: In nucleophilic substitution reaction, an atom or

group of atoms attached to carbon atom of an organic compound is substituted by

Nucleophile.

b) Addition reactions: When one molecule get added with another molecule containing

double or triple bond to form product where all the masses of reactants and product

became same. The reaction is called as addition reaction.

An addition reaction is initiated by electrophile is called as Electrophilic addition

reaction.

An addition reaction is initiated by nucleophile is called as Nucleophilic addition

reaction.

c) Elimination reactions: when two atoms or groups are removed without any

substitution then the reaction is called as elimination reaction.

In elimination reaction two atoms or groups are removed which are present on

adjacent carbon atoms are called as α-ß elimination, e.g.

In elimination reaction two atoms or groups are removed which are present on

same carbon atoms are called as α-α elimination, e.g.

d) Rearrangement: It involves the migration of atom or group from one position to

another position within the molecule to form structural isomer of the original compound.

e.g. Phenyl acetate in the presence of an. AlCl3, undergoes rearrangement to form a

mixture of o- & p-hydroxy acetophenone.

Reactive Intermediates:

The compounds or charged species or radicals formed during the reaction are called as

reactive intermediates. Reactive intermediates are short-lived, highly reactive species, generated by

bond breaking. Identification of these species helps to decide the pathway of the mechanism of the

reaction. Some important reaction intermediates are as follows

1) Carbocation, 2) carbanion, 3) Free radicals, 4) Carbenes, 5) Nitrenes and 6) Arynes.

1) Carbocation:

+vely charged carbon species is called as carbocation or carbonium ion. The +ve carbon

atom is bonded to three other atoms and has no nonbonding electrons. It is SP2 hybridized with a

trigonal planner structure and bond angles of about 120º. The unhybridized Pz orbital is vacant

and lies perpendicular to the plane of C-H bonds, e.g. CH3+.

In carbocation, carbon atom has only six electrons in its valence shell, to complete its octet it

requires two electrons. So it acts as electron deficient species i.e. electrophile and readily reacts with

negatively charged Nucleophiles.

The order of stability of carbocations is as follows:

Thus tertiary carbocation is most stable. It is stabilized by i) Inductive effect, & ii)

Hyperconjugative effect.

The inductive effect is a donation of electron density through sigma bonds of the molecule.

The +vely charged carbon atom withdraws some electron density from the alkyl group bnded to it.

Hence, greater delocalization of +ve charge over three methyl (alkyl) groups makes tertiary

carbocation more stable than secondary and primary carbocations.

Greater delocalization of +ve charge over nine hyperconjugative structures in tertiary butyl

carbocation makes it more stable than isopropyl carbocation (six hyperconjugative structures), ethyl

carbocation (three hyperconjugative structures), methyl carbocation (no hyperconjugative structure).

Methods of formation of carbocation:

1) from tert-alkyl halide:

tert-Butyl bromide on heating with aq. NaOH solution forms tert-butyl carbocation as an

intermediate.

2) By protonation of alkenes and alcohols;

Alkenes and alcohols in the presence of strong acids undergo protonation to form

carbocation.

Reactions of carbocations:

1) Rearrangement: Neo-pentyl bromide on hydrolysis undergoes SN1 reaction to give 2-

methyl-2-butanol and not the expected 2, 2-dimethyl-1-propanol.

In this reaction, less stable primary carbocation undergoes rearrangement to form

more stable tertiary carbocation to give 2-methyl-2-butanol as substitution product and 2-

methyl-2-butene as elimination by-product.

2) With nucleophiles: Carbocation combines with Nucleophiles, undergo elimination and

rearrangement to give different products.

2. Carbanions:

A carbanions is a species that contains triply bonded negatively charged carbon atom. There

are eight electrons around the carbon atom (three bonding electron pairs and one non-bonding lone

pair in valence shell). Hence, carbanion is electron-rich species and acts as nucleophile and base.

Electronic structure and hybridization of carbanion e.g. methyl carbanion is SP3 hybridized and

tetrahedral. One of the SP3 hybrid orbital= possesses an unshared lone pair of electrons. Bond angle

is about 107º. Like the amines, carbanions are Nucleophilic and basic in nature.

The order of stability of carbanion is the opposite of that of carbocations and free radicals.

Alkyl groups are electron releasing (donating) groups. Due to +I effect, three methyl groups

in tert-butyl carbanion increase electron density on central carbon resulting in less delocalization of –

ve charge (increase in electron density on central carbon atom). In methyl carbanion, there is no

presence of electron donating methyl group on central carbon atom. Hence, methyl carbanion is most

stable that primary, secondary and tertiary carbanions.

Methods of formation of carbanions:

1) By the decomposition of carboxylate anions: Carboxylate anion, formed by ionization of

acid in solution, on decomposition gives carbanions.

2) By the abstraction of proton: aldehydes and ketones possessing α-H atom on heating with

base loses proton to form carbanion.

Reactions of carbanions:

i) Addition reactions: Carbanion generated from Grignard Reagent on addition with CO2 to

form carboxylic acid. e.g. methyl magnesium bromide reacts with carbon dioxide in ether

gives acetic acid.

ii) Aldol reaction: aldehydes having α-H atoms, on treatment with alkali solution undergo self

condensation reaction to form ß-hydroxy aldehydes, called as aldol. In this reaction, one

molecule of aldehyde, in the presence of base, forms carbanion which reacts with another

molecule of aldehyde to form aldol.

3. Free Radicals:

Free radical is a highly reactive species in which an atom or group of atoms possesses an

unpaired (odd) electron. A radical is named by writing the name of the atom or group it contains and

then the word “radical”. e.g. Cl˙ as chloride radical, ˙CH3 as methyl radical etc.

In carbon radicals, e.g. methyl radical, carbon atom is SP2 hybridized Pz orbital lies

perpendicular to the plane of three C-H bonds and possesses an odd electron.

In methyl radical around carbon atom, there are seven electrons. It requires one electron to

get stable octet state. Hence, like carbocation, free radicals are electron deficient and act as

Electrophiles. The order of stability of free radicals is same as that of carbocations because both the

species are stabilized by hyperconjugation.

Tert-butyl radical is stabilized by nine hyperconjugative structures and no hyperconjugative

structure for methyl radical. Hence, tert-butyl radical is more stable than iso-propyl radical (six

hyperconjugative structures), ethyl radical (three hyperconjugative structures) and methyl radical (no

hyperconjugative structure). Greater is the number of hyperconjugative structures indicates more

delocalization of odd electron over entire radical species.

Formation of free radicals:

1) By photolysis: Acetone in the vapour phase in presence of UV light undergoes

decomposition to give methyl radical.

2) By thermolysis: Tetra ethyl lead in the vapour phase on thermal decomposition generates

four ethyl radicals.

(C2H5)4Pb 4 ˙C2H5 + Pb

Reactions of free radicals:

1) Addition of HBr: In the presence of benzoyl peroxide, the addition of HBr to unsymmetrical

alkenes occurs via anti-Markownikov rule. The reaction is called as peroxide effect.

2) Halogenation: Alkanes undergo chlorination either thermally or photochemically to give a

mixture of corresponding chloroderivatives. e.g.

4. Carbenes (Methylenes):

Carbenes are short lived neutral species in which one carbon atom possesses two bonds

(divalent) and two electrons either paired or unpaired. In carbine, there are six electrons around the

central carbon atom. Hence, just like Lewis acid, it acts as electron deficient species. The simplest

member of the class is non-isolable species of the formula: :CH2, e.g. :CCl2 as dichlorocarbene,

Ph2C: as diphenyl carbine, CH3COC¨H as acetocarbene etc.

There are two types of carbenes (i) Singlet carbene & (ii) Triplet carbene. The carbon atom

in singlet carbene e.g. in dibromo carbene, is SP2 hybridized, with trigonal planner geometry.

An unshared pair of electrons occupies one of the SP2 hybrid orbitals as paired pair and Pz

orbital which lies perpendicular is vacant.

It is called as singlet carbene. It possesses more energy due to repulsion between electrons

and hence it is comparatively unstable.

In triplet carbene, carbon atom is SP hybridized with linear geometry. Two SP hybrid orbitals

are involved in the formation of two sigma bonds and remaining two electrons are placed, one each,

in the equivalent mutually perpendicular Py and Pz orbitals, as unpaired pair.

These electrons have parallel spins. There is no chance of repulsion. Hence, triplet state

carbene possesses less energy and more stable than singlet carbene.

A singlet carbene may act as Lewis base as it can donate its non-bonded electron pair. It can

also acts as Lewis acid by accepting two electrons in its vacant Pz orbital. A triplet carbene acts as a

diradical.

Generation of Carbenes:

i) From Carbanions: Chloroform on hydrolysis with alkali solution first forms carbanion

which then loses chloride ion to form dichlorocarbene.

ii) By decomposition reaction: Diazomethane and ketene on pyrolysis or irradiation with UV

rays gives carbene.

Reactions of carbene:

i) Cycloaddtion reaction: Carbenes react with alkenes to form cycloalkanes.

ii) Reaction with nucleophile: Carbenes reacts with Nucleophiles like alcohols to give

corresponding ethers. In this reaction, carbene inserts into the OH bond of an alcohol.

5. Nitrenes:

Nitrenes are non-isolable, short lived, highly reactive and electron deficient species like

carbenes having six electrons on a nitrogen atom. Nitrenes are also called as azenes, imines, and

imidogens. The simplest nitrene is H—N, acyl nitrene RCO—N and alkyl nitrenes R—N are also

known.

Generation of Nitrenes:

i) From N-bromoamides: In Beckmann reaction, N-bromo amides on treatment with alkali

solution undergo elimination to form nitrenes.

ii) Photolysis: Hydrazoic acid and alkyl isocyanate on photolysis gives nitrenes.

Reactions of Nitrenes:

i) Addition Reaction: Nitrenes undergo addition reaction to give cyclic product, i.e. aziridine.

ii) Rearrangement: Acyl nitrenes undergo rearrangement to form alkyl isocyanates.

6. Aynes:

1, 2-Dehydrobenzene and its derivatives may be called as arynes or benzynes. The simplest

member is benzyne. It is a non-isolable highly reactive species.

The real structure of benzyne can be considered as a resonance hybrid of the following

resonating structures.

Triple bond in benzyne is not like the triple bond of acetylene. Benzyne has hexagonal

planner geometry with six delocalized π electrons. Third π bond between C1 and C2, called as

benzyne bond, is formed due to sidewise overlapping between two SP2 hybrid orbitals of C1 and C2,

each containing one electron. Electrons of benzyne bond do not interact with π electron cloud

involving Huckel number of π electron (6 π electrons) and they do not affect the aromaticity of the

benzyne molecule. Benzyne bond is unstable and therefore benzynes are extremely reactive

chemical species.

Methods of generation of Benzyne:

i) From bromobenzene: Bromobenzene on treatment with sodamide in liq. NH3 at -33ºC

generates benzyne.

ii) By thermal decomposition: Diazonium salt of antralinic acid on thermal decomposition in

benzene gives benzyne.

Reactions of Benzyne:

i) With ammonia: Benzyne reacts with ammonia to form aniline.

ii) Dimerization: Benzyne undergoes dimerization to form bephenylene.

Methods of Determination of Reaction Mechanism:

In a chemical reaction, a reactant molecule is converted into product molecule. The change is

associated with redistribution of electrons and involves some definite steps. An organic reaction

mechanism is a detailed study of the transformation which gives information regarding the number

of steps involved and sequence of breaking and making of bonds. Some chemical reactions proceed

very rapidly. Hence it is not possible to follow the reaction path directly. In such case, one has to

follow indirect evidence. Following are commonly used methods for determining the mechanism of

a reaction.

a) Product analysis,

b) Presence of intermediates,

c) Isotope effects,

d) Stereochemical evidence,

e) Kinetic evidence,

The proposed mechanism determined by the above methods should be

i) energetically reasonable,

ii) consistent with the experimental observation,

iii) In agreement with similar other analogous reaction.

1) Product Analysis:

The most fundamental information about the reaction mechanism is provided by establishing the

structure of the product, by-products and determining their relative quantities.

e.g. Two isomeric allyl chloride, 1-chloro-3-methyl-2-butene (I) and 3-chloro-3-methyl-1-

butene (II) on hydrolysis with alkali solution yields a mixture of 85% of tertiary alcohol (IV) and

15% of a primary alcohol (III) as products. The formation of these products (III & IV) can be

explained only on the basis of formation of intermediate corresponding carbocations A and B. these

carbocations, even though they are formed from different reactant molecules, are resonating

structures of each other. B carbocation, being tertiary, is more stable than A primary carbocation and

forms more % of tertiary alcohol (IV) as product.

Therefore, I and II reactants, as they form common intermediates, give 85% of tertiary

alcohol (IV) & 15% of primary alcohol (III).

Example-2: p-Chloro toluene on treatment with sodamide and liq. Ammonia at -33ºC

gives a mixture of p-toluidine as expected product and m-toluidine as unexpected product.

The formation of m-toluidine indicates that this reaction does not follow normal direct

substitution reaction. The reaction must take place through the formation of intermediate

which should give a mixture m- & p-toluidine as products. It is possible only due to the

formation of corresponding benzyne. Hence, the overall proposed reaction mechanism must

be as follows.

Formation of methyl benzyne is confirmed by isotopic labeling and spectroscopic methods.

Thus, establishment of the structure of products, by-products and determining their relative

quantities help us to arrive at the correct mechanism of the reaction.

2) Determination of the presence of Intermediates:

Many organic reactions take place through the formation f intermediates which canbe

isolated, detected by spectroscopy or trapped by chemical reaction with an added compound. We can

propose the correct mechanism by establishing the structure of intermediate.

Example-1:

In Hofmann rearrangement, an amide on treatment with Br2/KOH solution gives a primary

amine. Before completion of the reaction, intermediates formed in this reaction like N-bromo amide

(RCONHBr) its anion (RCO N Br) and an isocyanate (RNCO) have been isolated. Thus any

proposed mechanism for the Hofmann rearrangement must account for the formation of all these

intermediates. Proposed mechanism is as follows:

Example-2:

In Reimer-Tiemann reaction, phenol on treatment with chloroform & NaOH solution gives o-

hydroxy benzaldenyde. Proposed mechanism involves the formation of dichlorocarbene which is

confirmed by carrying out the same reaction in the presence of cis-2-butene to form corresponding

cyclopropane derivative. It can be isolated as by-product. It is called as trapping of carbene. On the

basis of confirmation of dichlorocarbene, the following mechanism can be proposed for Reimer-

Tiemann reaction.

3) Isotope effects:

When one of the bonded atoms is substituted by its heavier isotope, the rate of bond breaking

becomes slower. The greater mass of the isotope makes the bond stronger and hence the bond breaks

more slowly e.g. C—D bond breaks at a slower rate than a C—H bond. So by comparing the rate of

the original bond breaking with that of the heavier isotope substituted bone, one can determine

whether a particular bond breaks in the rate determining step or not. The effect of heavier isotope

substitution on rate of the bond breaking is said to be primary kinetic isotope effect. e.g. in the

oxidation of secondary alcohol.

It is found that Ph2CHOH is oxidized 6-7 times as rapidly as Ph2CDOH, the reaction is said to

exhibit a primary kinetic isotope effect and breaking of the C—H bond must clearly be involved in

the rate limiting step of the reaction. On the other hand, benzene C6H6 and hexadeutero benzene,

C6D6 are found to undergo nitration at essentially the same rate i.e. there is no primary kinetic

isotope effect. it shows that C—H bond breaking is not involved in the rate determining step but it is

C—NO2 bond formation is involved in the rate determining step.

Which bond of a molecule breaks can also be determined without kinetic study, i.e. in ester

molecule, there are two C—O σ bonds, (one is acyl—oxygen and there is alkyl—oxygen). Ester is

hydrolyzed using water solvent enriched with H18OH.

If ester undergoes hydrolysis with acyl—oxygen cleavage, 18O atom will be found in the

acid.

If ester undergoes hydrolysis with alkyl—oxygen cleavage, the alcohol will contain 18O

atom.

Acid and alcohol are isolated and they are subjected to mass spectroscopic study to detect the

presence of 18O. If we get 18O atom in isolated acid, it indicates that ester undergoes hydrolysis with

alkyl—oxygen cleavage.

4. Stereochemical evidence:

The mechanism of organic reaction can also be explined by following its stereochemistry.

e.g. Nucleophilic substitution reactions whether it is SN1 or SN2, can be investigated by performing

experiments with optically active compounds and then checking optical activity of the products. If a

Nucleophilic substitution reaction with optically active reactant takes place with the formation of

recemic mixture (optically inactive) product, it indicates that the reaction follow SN1 pathway. It

must involve the formation of planner carbocation which is equally attacked by the nucleophile on

either side producing a mixture of equal number of optical isomers.

If nucleophilic substitution reaction with an optically active reagent takes place with the formation of

product having opposite configuration, it indicates that the reaction follows SN2 pathway. The

mechanism must involve the attack of nucleophile (OH¯) on carbon atom of reactant from a side

opposite to leaving group which results in the formation of product with opposite configuration

(inversion of configuration).

5. Kinetic evidence:

Kinetics is the study of reaction rates. The rate of reaction is how fast the products appear

and the reactants disappear. We can determine the rate by measuring the increase in the

concentrations of the products with time. Reaction rates depend on the concentration of the reactants.

The greater the concentrations, the more often the reactants collide and the greater the chance of

reaction.

The order of reaction is the number of atoms or molecules whose concentration determine the

reaction velocity. According to this, the reaction is first, second and third order depending on

whether concentration of one reactant, two reactants or three reactants determine the reaction

velocity. According to the law of mass action, velocity of chemical reaction is proportional to the

product of active masses of interacting reactants at that moment.

The expression (equation) that relates the rate of reaction and the concentration of reactants is

called the kinetic expression for the reactants. The order of reaction can be determined

experimentally. Then we can use this information to propose consistent mechanism. e.g. Hydrolysis

of methyl bromide with aq. NaOH.

The reaction is carried out at a specific temperatute hecause reaction rates are known to be

temperature dependant. The rate of the reaction can be determined experikmentally by measuring the

rate at which methyl bromide or (OH¯) ions disappear from the solution or the rate at which

methanol or bromide ions appear in the solution; several experiments are to be performed keeping

the same temperature but varying the initial concentration of the reactants.

Experiments showed that the rate of reaction depends on the concentration of both methyl

bromide and hydroxide ions; we can express these results as

Rate α (CH3Br) (OH¯)

Rate = K (CH3Br) (OH¯)

Where K is called rate constant.

Hence, hydrolysis of primary alkyl halide with alkali solution, reaction is said to be second

order. Moreover, it is bimolecular because two reactants are involved in rate determinging step. It is

designated as SN2.

In another reaction, tert-butyl bromide in water/acetone mixture is heated with aq. NaOH

solution to obtain tert-butyl alcohol and NaBr.

After performing several experiments keeping the temperature the same but changing the

initial concentration of the reactants, it was found that the rate of formation of tert-butyl alcohol is

dependant on the concentration of hydroxide ions. Doubling the tert-butyl bromide concentration,

doubles the rate of reaction but changing the hydroxide ion concentration has no appreciable effect.

thus the rate equation for this substitution reaction is first order with respect to tert-butyl bromide

and first order overall.

Rate α [(CH3)3Br]

Rate = K [(CH3)3Br]

Where K is rate constant.

We can therefore conclude that hydroxide ions do not participate in the transition state of the

step that controls the rate of reaction. i.e. only one reactant, tert-butyl bromide, is involved in the rate

determining step. Hence hydrolysis of tert-alkyl halide with alkali solution is unimolecular and first

order and is designated as SN1.