UPCT(3140508)

Semester – IV (CHEM)
Chapter Name: Mechanisms and Recent advances of following
unit process

Halogenation is a chemical reaction that involves the addition of one or more halogens to a
compound or material. The pathway and stoichiometry of halogenation depends on the structural
features and functional groups of the organic substrate, as well as on the specific halogen.
Inorganic compounds such as metals also undergo halogenation.

Halogenation by reaction type

Free radical halogenation

Saturated hydrocarbons typically do not add halogens but undergo free radical halogenation,
involving substitution of hydrogen atoms by halogen. The regiochemistry of the halogenation
of alkanes is usually determined by the relative weakness of the available C–H bonds. The
preference for reaction at tertiary and secondary positions results from greater stability of the
corresponding free radicals and the transition state leading to them. Free radical halogenation
is used for the industrial production of chlorinated methanes:[1]
CH4 + Cl2 → CH3Cl + HCl
Rearrangement often accompany such free radical [Link] of halogens to
alkenes and alkynes
Unsaturated compounds, especially alkenes and alkynes, add halogens:
RCH=CHR′ + X2 → RCHX–CHXR′
The addition of halogens to alkenes proceeds via intermediate halonium ions. In
special cases, such intermediates have been isolated.
Other halogenation methods
In the Hunsdiecker reaction, from carboxylic acids are converted to the chain-shortened halide.
The carboxylic acid is first converted to its silver salt, which is then oxidized with halogen:
RCO2Ag + Br2 → RBr + CO2 + AgBr
The Sandmeyer reaction is used to give aryl halides from diazonium salts, which are
obtained from anilines.
In the Hell–Volhard–Zelinsky halogenation, carboxylic acids are alpha-halogenated.
In oxychlorination, the combination of hydrogen chloride and oxygen serves as the
equivalent of chlorine, as illustrated by this route to dichloroethane:
2 HCl + CH2=CH2 + 1⁄2 O2 → ClCH2CH2Cl + H2O

Halogenation by halogen type

The facility of halogenation is influenced by the halogen. Fluorine and chlorine are
more electrophilic and are more aggressive halogenating agents. Bromine is a weaker
halogenating agent than both fluorine and chlorine, while iodine is the least reactive of them all.
The facility of dehydrohalogenation follows the reverse trend: iodine is most easily removed from
organic compounds, and organofluorine compounds are highly stable.

Prepared By: Ms. Limbad Bharti Page

 UPCT(3140508)
Semester – IV (CHEM)
Chapter Name: Mechanisms and Recent advances of following
unit process

Fluorination
Organic compounds, saturated and unsaturated alike, react readily, usually explosively, with
fluorine. Fluorination with elemental fluorine (F2) requires highly specialised conditions and
apparatus. Many commercially important organic compounds are fluorinated electrochemically
using hydrogen fluoride as the source of fluorine. The method is called electrochemical
fluorination. Aside from F2 and its electrochemically generated equivalent, a variety of
fluorinating reagents are known such as xenon difluoride and cobalt(III) fluoride.

Chlorination
Chlorination is generally highly exothermic. Both saturated and unsaturated compounds react
directly with chlorine, the former usually requiring UV light to initiate homolysis of chlorine.
Chlorination is conducted on a large scale industrially; major processes include routes to 1,2-
dichloroethane (a precursor to PVC), as well as various chlorinated ethanes, as solvents.
Bromination
Bromination is more selective than chlorination because the reaction is less exothermic. Most
commonly bromination is conducted by the addition of Br2 to alkenes. An example of bromination
is the organic synthesis of the anesthetic halothane from trichloroethylene

Organobromine compounds are the most common organohalides in nature. Their formation
is catalyzed by the enzyme bromoperoxidase which utilizes bromide in combination with
oxygen as an oxidant. The oceans are estimated to release 1–2 million tons of bromoform
and 56,000 tons of bromomethane annually.[6]
Iodination
Iodine is the least reactive halogen and is reluctant to react with most organic compounds.
The addition of iodine to alkenes is the basis of the analytical method called the iodine
number, a measure of the degree of unsaturation for fats. The iodoform reaction involves
degradation of methyl ketones.

Electrochemical chlorination of toluene

The probable mechanism for the two-phase electrolysis The mechanism of this reaction seems to be
very simple, which is shown in Scheme 2. The substitution of hydrogen by chlorine in the side chain
chlorination is following a radical chain reaction.

Free radical chain reaction comprise of following three different steps: I. Initiation II. Propagation III.
Termination.

Initiation step In this step, the reactive intermediate chlorine atom is generated. The chloride ion
gets oxidized on the anode giving chlorine atom is the generation of a reactive intermediate: ashort
lived, highly reactive species that is never present in large concentrations due to its reactive nature.

Prepared By: Ms. Limbad Bharti Page

 UPCT(3140508)
Semester – IV (CHEM)
Chapter Name: Mechanisms and Recent advances of following
unit process

The reactive chlorine atom collides with a toluene molecule and abstracts a hydrogen atom.
One of the C H

bond electrons stays on the carbon atom. The first propagation step is the generation of the
reactive intermediate. The radical reacts and generate another radical. The reactive intermediate
thus produced (benzyl radical) reacts in the second propagation step. In the course of generation of
the product benzyl chloride, another chlorine radical is produced and thus the propagation
continues.

If a radical undergoes a reaction, which does not generate another radical, then the chain reaction
slows and stops. The termination steps involve the combination of two free radicals either of two
chlorine atoms or chlorine atom with benzyl radical.

Photochlorination
Photochlorination is a chemical reaction which is initiated by light, in which either hydrogen is replaced by
chlorine in a hydrocarbon compound or chlorine is reacted via an addition reaction to an aromatic or olefinic
hydrocarbon. Photochlorination is carried out in addition to thermal and catalytic chlorination on an industrial
scale, usually in the liquid phase, sometimes in the presence of inert solvents. The process is exothermic and
proceeds as a chain reaction initiated by the homolytic cleavage of molecular chlorine into chlorine radicals by
ultraviolet radiation.

The chlorinated hydrocarbons produced via photochlorination are often only industrial intermediates and
react with a large number of basic chemicals to secondary products such as alcohols, mercaptans, amines and

Prepared By: Ms. Limbad Bharti Page

 UPCT(3140508)
Semester – IV (CHEM)
Chapter Name: Mechanisms and Recent advances of following
unit process

carboxylic acids. The chemical industry uses low molecular weight chlorinated compounds, such as
tetrachloromethane, as solvents. Higher molecular-weight chloroalkanes serve as insecticides, as flame
retardants or as plasticizers in plastics and coatings. Chlorinated hydrocarbons are also used as intermediates
in the chemical industry for the production of silicones or detergents.

Nitration is a general class of a chemical process for the introduction of a nitro group into an
organic chemical compound. More loosely the term also is applied incorrectly to the different
process of forming nitrate esters between alcohols and nitric acid, as occurs in the synthesis of
nitroglycerin.

Nitration of Benzene
The source of the nitronium ion is through the protonation of nitric acid by sulfuric acid, which causes
the loss of a water molecule and formation of a nitronium ion.

Sulfuric Acid Activation of Nitric Acid

The first step in the nitration of benzene is to activate HNO 3with sulfuric acid to produce a stronger
electrophile, the nitronium ion.

Prepared By: Ms. Limbad Bharti Page

 UPCT(3140508)
Semester – IV (CHEM)
Chapter Name: Mechanisms and Recent advances of following
unit process

Because the nitronium ion is a good electrophile, it is attacked by benzene to

produce Nitrobenzene.

Mechanism

Sulfonation
:

Sulfonation is a reversible reaction that produces benzenesulfonic acid by adding sulfur trioxide and
fuming sulfuric acid. The reaction is reversed by adding hot aqueous acid to benzenesulfonic acid to
produce benzene.

Sulfonation of Benzene

Sulfonation is a reversible reaction that produces benzenesulfonic acid by adding sulfur trioxide and
fuming sulfuric acid. The reaction is reversed by adding hot aqueous acid to benzenesulfonic acid to
produce benzene.

Prepared By: Ms. Limbad Bharti Page

 UPCT(3140508)
Semester – IV (CHEM)
Chapter Name: Mechanisms and Recent advances of following
unit process

Mechanism

To produce benzenesulfonic acid from benzene, fuming sulfuric acid and sulfur trioxide are added.
Fuming sulfuric acid, also refered to as oleum, is a concentrated solution of dissolved sulfur trioxide
in sulfuric acid. The sulfur in sulfur trioxide is electrophilic because the oxygens pull electrons away
from it because oxygen is very electronegative. The benzene attacks the sulfur (and subsequent
proton transfers occur) to produce benzenesulfonic acid.

Reverse Sulfonation

Sulfonation of benzene is a reversible reaction. Sulfur trioxide readily reacts with water to produce
sulfuric acid and heat. Therefore, by adding heat to benzenesulfonic acid in diluted aqueous sulfuric
acid the reaction is reversed.

Further Applications of Nitration and Sulfonation

Nitration is used to add nitrogen to a benzene ring, which can be used further in substitution
reactions. The nitro group acts as a ring deactivator. Having nitrogen present in a ring is very useful

Prepared By: Ms. Limbad Bharti Page

 UPCT(3140508)
Semester – IV (CHEM)
Chapter Name: Mechanisms and Recent advances of following
unit process

because it can be used as a directing group as well as a masked amino group. The products of
aromatic nitrations are very important intermediates in industrial chemistry.

Because sulfonation is a reversible reaction, it can also be used in further substitution reactions in
the form of a directing blocking group because it can be easily removed. The sulfonic group blocks
the carbon from being attacked by other substituents and after the reaction is completed it can be
removed by reverse sulfonation. Benzenesulfonic acids are also used in the synthesis of detergents,
dyes, and sulfa drugs. Bezenesulfonyl Chloride is a precursor to sulfonamides, which are used in
chemotherapy.

OXIDATION
Oxidation is any chemical reaction that involves the moving of electrons. Specifically, it means the
substance that gives away electrons is oxidized.

When iron reacts with oxygen it forms a chemical called rust because it has been oxidized.

Process:

In the Amoco process, which is widely adopted worldwide, produces terephthalic acid by
oxidation of p-xylene using oxygen in air:

The process uses a cobalt–manganese–bromide catalyst. The bromide source can be sodium
bromide, hydrogen bromide or tetrabromoethane. Bromine functions as a regenerative source of
free radicals. Acetic acid is the solvent and oxygen from compressed air is the oxidant. The
combination of bromine and acetic acid is found to be highly corrosive, requiring specialized
reactors, such as those lined with titanium. A mixture of p-xylene, acetic acid, the catalyst system,
and compressed air is fed to a reactor.

Mechanism
The oxidation of p-xylene proceed by a free radical process. Bromine radicals decompose cobalt
and manganese hydroperoxides. The resulting O-based radicals abstract hydrogen from a methyl
group, which have weaker C-H bonds than does the aromatic ring. Many intermediates have been
isolated. p-xylene is converted to p-toluic acid, which is less reactive than the p-xylene owing to
the influence of the electron-withdrawing carboxylic acid group. Incomplete oxidation produces 4-
carboxybenzaldehyde (4-CBA), which is often a problematic impurity.

Prepared By: Ms. Limbad Bharti Page

 UPCT(3140508)
Semester – IV (CHEM)
Chapter Name: Mechanisms and Recent advances of following
unit process

Alternative reaction media

The use of carbon dioxide overcomes many of the problems with the original industrial process.
Because CO2 is a better flame inhibitor than N2, a CO2 environment allows for the use of pure
oxygen directly, instead of air, with reduced flammability hazards. The solubility of molecular oxygen
in solution is also enhanced in the CO2 environment. Because more oxygen is available to the
system, supercritical carbon dioxide (Tc = 31 °C) has more complete oxidation with fewer
byproducts, lower carbon monoxide production, less decarboxylation and higher purity than the
commercial process.

In supercritical water medium, the oxidation can be effectively catalyzed by MnBr2 with pure O2 in a
medium-high temperature. Use of supercritical water instead of acetic acid as a solvent diminishes
environmental impact and offers a cost advantage. However, the scope of such reaction systems is
limited by the even harsher conditions than the industrial process (300−400 °C, >200 bar).

Hydrogenation
It is a reduction reaction which results in an addition of hydrogen (usually as H2). If an organic
compound is hydrogenated, it becomes more "saturated" with hydrogen atoms. The process
typically requires the use of a catalyst, since hydrogenation only occurs spontaneously at high
temperatures.

Prepared By: Ms. Limbad Bharti Page

 UPCT(3140508)
Semester – IV (CHEM)
Chapter Name: Mechanisms and Recent advances of following
unit process

Reductive amination:

Reductive amination (also known as reductive alkylation) is a form of amination that involves the
conversion of a carbonyl group to an amine via an intermediate imine. The carbonyl group is most
commonly a ketone or an aldehyde. It is considered the most important way to make amines, and a
majority of amines made in the pharmaceutical industry are made this way.

ay you have a primary amine such as benzylamine and would like to make N-methylbenzylamine.
How do you do it?

Direct treatment of benzylamine with an alkylating agent (e.g. methyl iodide, CH3I ) will result in
significant formation of the undesired tertiary amine (i.e. di-alkylation).

Yes, you could try and separate out the secondary amine that’s formed from the tertiary amine, but
we’re not going to settle for 10-30% yields here. Separating mixtures is fine on paper, but (trust me
on this) it can be a real a pain in practice. Is there another way to do it?

2. Reductive Amination To The Rescue

Enter reductive amination!

While alkylation can happen multiple times on an amine, imines only form once on a given amine.
Once the imine is formed, the C=N bond can be reduced, giving us a new alkyl group attached to
nitrogen.

This is a much more controlled manner of forming nitrogen-carbon bonds.

Prepared By: Ms. Limbad Bharti Page

 UPCT(3140508)
Semester – IV (CHEM)
Chapter Name: Mechanisms and Recent advances of following
unit process

Prepared By: Ms. Limbad Bharti Page

 UPCT(3140508)
Semester – IV (CHEM)
Chapter Name: Mechanisms and Recent advances of following
unit process

Prepared By: Ms. Limbad Bharti Page

 UPCT(3140508)
Semester – IV (CHEM)
Chapter Name: Mechanisms and Recent advances of following
unit process

Prepared By: Ms. Limbad Bharti Page

 UPCT(3140508)
Semester – IV (CHEM)
Chapter Name: Mechanisms and Recent advances of following
unit process

Prepared By: Ms. Limbad Bharti Page

 UPCT(3140508)
Semester – IV (CHEM)
Chapter Name: Mechanisms and Recent advances of following
unit process

Prepared By: Ms. Limbad Bharti Page