chapter - 1 using new reagent systems...

Introduction

CHAPTER - 1

AN INTRODUCTION TO HALOGENATION OF ORGANIC COMPOUND S

USING NEW REAGENT SYSTEMS

1. INTRODUCTION

Halogenation is a chemical reaction in which compound usually a compound

compound react with a halogen or chemical reaction where a halogen atom combined

with the organic molecule. More specifically it is defined as chlorination,

bromination, iodination and fluorination. It is an organic reaction investigated and

discussed thoroughly in a wealth of halogenation chemical literature1. The product

formed during halogenation process are employed in various ways, such as polymer

intermediates, refrigerants, insecticides, fumigants, sterilants, additives for gasoline,

and materials used in fire extinguishers.

In chemical defense role various halogenated compounds plays a very important role

to keep predators away from a particular organism. Other areas of application of

halogenated compound is in pharmacological interest due to their wide range

biological activities, these include antifungal, antibacterial, antineoplastic, antiviral,

anti-inflammatory, and additional biological activities also. The structural features

and types of functional grouppresent in an organic substrate as well as the type of

halogen used, all these determine the pathway and stoichiometry of halogenation

reactions for example Alkenes readily react with halogens if reaction carried out

under standard laboratory conditions.

The halogenation reactions of organic substrates requires of halogens like chlorine,

bromine, or iodine. There are various processes for the halogenation of various

halogenation compounds such as free radical halogenation, which is mainly done for

the saturated hydrocarbons as they do not add halogens, ketone halogenation This

reaction is associated with serious environmental hazards with respect to handling,

transportation and storage of fluorine, chlorine, bromine, and iodine4. Halogenation

reactions can be divided according to the type of halogen: fluorination, chlorination,

bromination, and iodination.

Introduction

The direct halogenation system Br2 doesn’t react at low temperature in noticeable

manner with Cl2. But in presence of catalytic system such as Al-Hg, C6H5N or Fe,

reaction process takes place readily, the monohalogenated derivative afforded as a

main product in first instance. Mostly the p-isomers of di-substituted products were

obtained if we increase the proportion of halogen.

1.1 Iodination:

Few such typical procedures are known like bromobenzene. The catalyst use helps to

increase electrophilic activity of the halogens. The iodination can be carried out by

using the oxidizing agent because iodine is less reactive among all halogens. The

nature of electrophile which functions as I+ when using fuming nitric acid as a

catalyst, I+ thought to be [O=N (I) OH] +. CuCl2 is being recently used as a source of

oxidant in the presence of Aluminium Chloride.

In both the methods, iodobenzene was obtained in good yield but the later method is

more suitable for the iodination of alkylbenzenes. Aromatic hydrocarbons which are

condensed easily react with electrophilic reagent. Example Naphthalene is readily

brominated in solution in carbon tetrachloride without using any catalyst.

In side chain halogenation of toluene using chlorine or bromine, took place with the

exposure to sunlight or other bright light. The reaction does not require any catalyst.

The first chlorine atom and the reaction results in the formation of benzyl chloride

first then benzylidene chloride and at last benzotrichloride are formed.

The replacement of hydrogen atom from an aromatic compound by a chloromethyl

(CH2Cl) group is called chloromethylation. Originally the reaction consists of the

interation of formaldehyde and hydrogen chloride in the presence of a catalyst like

aluminium chloride or zinc chloride with an aromatic system (Blanc chlomethylation

reaction).

In case of aromatic compounds, free amino group strongly activate the aromatic ring

for the electrophilic attack and aromatic substitution of amines that ultimately results

in polysubstitution. The aniline and o-toluidine undergoes through iodination usin

iodine in the presence of sodium hydrorbonate or calcium carbonate resulted in

Introduction

substituent entering the para position to the amino group. Further other chloro

compounds are also used for the mono-chlorination of aromatic amines. Examples: -

NCS which largely restricted the chlorination of aniline to monosubstitution.

Halogenation of acetic acid using gaseous chlorine in the presence of red phosphorus

results in formation of mono, -di, and triacetic acid (CO2Cl) CO2H, CH2Cl.COOH and

CCl3.CO2H respectively. However on the other hand Bromination of acetic acid is

highly selective and only α-bromo acetic acid is obtained when reaction is carried out

in the presence of reagent such as red phosphorous of phosphorous trichloride or

tribromide (Halogenation of carboxylic acid).

Halogenation of aqueous solution of phenol with bromine water yields in precipitate

of 2, 4, 6-tribromophenol. However the mono-bromination of phenol with can be

achieved by using the solutions of bromine in non polar solvents like carbon

disulphide and carbon tetrachloride at very low temperature ie. 0-5 οC and the product

obtained is exclusively the para isomer.

There are various methods/procedures for the preparation of aromatic halogen

compounds including direct halogenation which is done either by substitution in the

nucleus or by the substitution in the side chain of aromatic compounds,

chloromethylation, or by replacement of a diazo group by the halogen and through

replacement of hydroxyl group by the halogen.

1.2 Bromination:

The unsaturated organic compounds are readily converted in to saturated compounds

when reacted with halogens (chlorine, bromine, iodine). However iodine reacts very

slowly. The addition of halogens readily proceeds at room temperature or below by

mixing together the two reactants ie. Unsaturated compounds and halogens. The high

temperature and excessive amount of halogens leads to conditions where substitution

might become an important side reaction.

Introduction

C=C + X2 C - C

X X

Alkene X2=Cl2, Br2 Vicinal

dichlorode

Mechanism of addition of halogens: Halogens are attached to the unsaturated

compounds through electrophilic addition that involved two steps.

In the first step, a cation is formed but in most cases this cation is not a carbon but

something now ie. halonium ion. Example, In case of bromine firstly bromine is

transferred from bromine molecule to the unsaturated compound (for example alkene)

in such a way that is attached to both the carbon forming a cyclic Bromonium ion.

This step does not represent electrophilic addition. However in this the Bromine is

transferred as positive bromine and left newly formed bromide ion.

In second step this bromide ion reacts with the bromonium ion and results in the

formation of product ie. dibromide.

Br - Br + C = C Br- and - C - C -

Br+

Bromide ion Bromonium ion

- C - C -

Br+

Br-+ - C - C -

+Br

dibrom ide

Introduction

The insertion of bromine atom into the organic molecule with its simultaneous

oxidation is called oxybromination. The bromonium ion (Br+) along with counter ion

(mainly OH-) is the main active species in oxybromination reactions.

The bromonium ion provided directly in the solution by brominating reagent or

alternately it is generated in-situ from the oxidation of bromide (Br-) using suitable

oxidant in particular reaction conditions. The later strategy is more favorable than

former one and it is widely utilized. The oxybromination reactions are vital for the

synthesis of various important bromoderivatives: bromohydrins, α-bromoketones and

α, α-dibromoketones as well as for other useful organic synthesis.

Bromination of organic compound is one of the popular industrial processes due to

multiple uses like: In water purification, agriculture, healthcare, photography etc.

Organic compounds are brominated by either addition or substitution reactions.

Bromine undergoes addition to the unsaturated hydrocarbons (alkenes and alkynes)

via a cyclic bromonium intermediate. In non-aqueous solvents such as carbon

disulfide, it gives di-bromo products.

For example, reaction of bromine with ethylene will produce 1, 2-dibromoethane as

product. When bromine is used in presence of water, a small amount of the

corresponding bromohydrin will form along with desired dibromo compounds.

Bromine also gives electrophilic nuclear bromination of phenols and anilines.

Due to this property, bromine water was employed as a qualitative reagent to detect

the presence of alkenes, phenols and anilines in a particular system. Like the other

halogens, bromine also participates in free radical reactions. Classical bromination of

aromatics, for example, utilizes only 50% of the halogen, with the other half forming

hydrogen bromide.

---- (1)

Introduction

Though bromine has many applications in chemistry as a reagent, it has some

disadvantages also whenever disposed to environment. Some bromine-related

compounds have been evaluated to have an ozone depletion potential or bio

accumulate in living organisms. As a result, many industrial bromine compounds are

no longer manufactured and are being banned.

Theoretically, it is possible to reoxidise the Hydrogen Bromide, e.g. with H2O2, and

achieve high bromine utilization, between 90 and 95%.

----- (2)

Thus, activated aromatic, like as phenols, anisols, and anilines, may be oxybrominated

without catalyst, while inactive (benzene, toluene) but not deactivated ones, have been

oxybrominated in the presence of quaternary ammonium salts.

Practically, however HBr recycling is rarely performed in industrial processes, as the

additional step and the corrosiveness of HBr necessitate reactor costs that exceed

those of purchasing more Br2.

Free radical halogenating reaction and its reactivity:

Many reactions in earlier chapters have ionic reagents and ionic intermediates.

The reactions in this chapter involve electrically neutral free radicals. These

reactions include free radical halogenations of alkanes and free radical additions to alkenes.

R3C - H +X 2 R3C - X + H - X

Alkane Halogenation

Alkene Addition

R2C - CR 2 + X - Y R2CX - CYR 2

Introduction

Some aspects of these reactions cause them to be more complex than ionic reactions.

In order to address these details adequately without overwhelming this general presentation,

we include some topics in "Asides" (in small font) in this chapter text, while some are in

Appendices at the end of the chapter.

Free Radicals

Important free radicals that we see in this chapter include halogen atoms (X.),

alkoxy radicals (RO.), and carbon free radicals (R3C.).

Halogen Atoms. The atoms in column 7A of a periodic table are the halogen atoms.

Of these, chlorine (Cl) and bromine (Br) atom are particularly important in the free

radical reactions that we describe here. To clearly contrast them with halide ions (X.),organic chemists often write halogen atoms as X. where the (.) is an unshared e

-.

As with all atoms, each halogen atom has the same number of electrons

as it has protons and that is why it is electrically neutral. In contrast, halide

ions (X:-) are negatively charged because each has one more electron

than it has protons (table 1.1)

X. Protons electrons X:- Protons electrons

F. 9 9 F:- 9 10

Cl. 17 17 Cl:- 17 18

Br. 35 35 Br:- 35 36

I. 53 53 I:- 53 54

Introduction

We represent halide ions as X:- that shows the reactive unshared electron pair.

We obtain the symbol X. for the neutral halogen atom by simply remaining one

electron with a-1 charge (an e

-) form X:

-. We can also visualize the meaning

of X. by picturing its formation from its parent molecular halogen X2.

X2 or X - X or X : X X. .X

The covalent bond between the two halogen atoms (X - X) is an electron pair)

(X : X). When thet bond breaks homolytically (undergoes homolysis), each

halogen atom retains one of the two electrons in that bond

Alternatively, we can visualize the formation of the molecular halogen X2

from indivisual halogen atoms.

X. .X X : X or X - X or X2

Halogen atoms are highly reactive. They do not exist alone, but in molecules

such as X2, H-X or CH3

-X, where they are bonded to other atoms. We will

see at the end of this section why organic chemists also refer to halogen atoms such as free radicals.

Alkoxy radicals. Another free radical in this mechanism is the alkoxy (or alkoxyl)

radical (RO.). We saw alkoxide ions (RO:-) in earlier researches where they

were nucleophiles and also strong bases. Alkoxy radicals (RO.) are also highlyreactive, but they are electrically neutral. You can see that they are electrically neutral by imagining their formation from alkoxide ions by removal of one e

-.

Introduction

Oxidation of bromides to bromine according to this invention typically takes place in

a commercial setting in a packed column with addition of the reagents and steam in a

continuous system using hydrogen peroxide as an oxidant for bromine production;

however, variations are possible as will be familiar to those skilled in the art.

This invention provides that bromine can be derived from about 0.01 wt % to about

60 wt % HBr, about 3 wt % to about 70 wt % H2O2, about 0.03 wt % to about 0.5 wt

% catalyst according to this invention and about 5 wt % to about 20 wt % HCl, all

based on the sum of the weights of the HBr, the H2O2, the catalyst, and the HCl prior

to each being used in the bromine derivation.

Typically, the bromide source, the oxidant, and the catalyst, and when included, the

hydrogen chloride or mineral acid, are in aqueous solution. This invention also

provides that the molar ratio of bromide source to catalyst according to this invention

can be from about 150:1 to about 1200:1, or about 200:1 to about 1000:1, or about

400:1 to about 900:1, or about 600:1 to about 850:1, or about 858:1 to about 831:1.

The major issue is transportation and storage of large quantities of molecular bromine

and HBr is extremely hazardous. These risk factors can be reduced by bromide

recycling. Several recent publications cite toxicity of Br2 and HBr as the incentive to

investigate various comples oxybromination reagents.

Neurocardiogenic syncope is a well-defined cardiovascular condition, its cause,

however is still poorly understood. Although seveveral pathophysiologic

interpretations regarding its cause have been proposed, various mechanisms may

contribute to the cause in different subjects or even simultaneously in one subject.

But in real life two situations have to be distinguished:

(a) When molecular bromine is available on site, it is the cheapest and most

environmental friendly brominating reagent.used in conjugation with H2O2, the

stoichiometry would then be

Introduction

H2O2 + 2Ar + Br2 2ArBr+ 2H2O

(b) When a bromine containing reagent has to ship to the site, only four reagents are

cheap enough to matter for large-scale manufacturing: Br2, HBr, KBr and NaBr.

1.3 Chlorination:

Chlorination of arenes is a prominent organic reaction with wide laboratory use and

industrial applications. The introduction of chlorine onto aromatic ring is an important

synthetic transformation because chlorinated compounds are recognized as versatile

starting materials and additives in the production of high quality insecticides,

fungicides, herbicides, dyes, pharmaceutical etc. therefore, there are several known

methods available in the literature that have been developed for the chlorination of

aromatic compounds.

A common method to introduce chlorine atom into organic substrates, whether they

are free radical processes or polar additions to olefinic groups or electrophillic

substitution on aromatic ones, involves the use of molecular chlorine which has high

vapor pressure or are gasses at room temperature and 1 atm pressure.

The dihalogens are corrosive, poisonous, and can be dangerous to handle, methods

that require their transport and manipulation are difficult. Generally, the chlorination

of arenes can be accomplished by using chlorinating agents such as t-butyl

hypochlorite in presence of zeolites, metal chloride-H2O2 in acid aqueous medium, m-

chloroperbenzoic acid/HCl/DMF. Sulfuryl chloride, acetyl chloride in presence of

ceric ammonium nitrate, SnCl4/Pb(OAC)4, HCl-H2O2 under microwave conditions,

N-chlorosuccinimide, etc.

Analyzing these literature data, one can see that the most promising example of

chlorination include a one pot synthesis where elemental chlorine is generated in-situ

by the use of haloacids in the presence of an oxidizing agent. Oxidative chlorination

Introduction

has emerged as an environmentally-benign process via the in-situ formation of

molecular chlorine from the oxidation of chloride with suitable oxidants.

Therefore, mono and biphasic oxidative process based on generating the chlorine

from concentrated HCl in presence of oxidant has been developed. Chlorination of

aromatic rings by HCl using H2O2, t-BHP and sodium perborate as oxidizing agents

have already been attempted. However, these methods involved the use of organic

solvents which have serious environmental impacts and also having disadvantages of

long duration, high temperature and use of catalyst.

Also, recently Podgorsek et al. have used HCl/H2O2 to transform aryliodides into

aryliodine (III) dichlorides in the presence of trifluoroethanol which act not only as

reaction medium but also as activator of hydrogen peroxide for oxidation of HCl into

molecular chlorine.

But, trifluoroethanol which is used in this system is toxic and harmful solvent and is

recommended to avoid the long term contact with skin. One of the key principles of

green chemistry is the elimination of solvent in chemical processes or the replacement

of hazardous solvent with environmentally-benign solvents.

Water is the most promising solvent because it is readily available, non-flammable,

non-toxic and could offer the easy separation of reagents or catalysts from many

organic products. Earlier the chlorination of substituted acetanilide (aromatic

compounds) in acid-aqueous medium was carried out by jerzy et al. by using metal

chloride-hydrogen peroxide system.

The drawbacks of this method are use of large amount of acid (HNO3) and

chlorinating agent (NaCl) with poor yield and selectivity. Our present method

overcomes all above limitations. Also, NaClO3 is low cost, easy to handle than H2O2,

t-BHP and has better solubility in water than sodium perborate, thus, making it a

useful reagent for carrying out reaction in water.

By considering these advantages of NaClO3 it has been successfully employed as a

convenient oxidant for oxidative chlorination in water. Also a perusal of the literature

Introduction

revealed that earlier Moon et al. have used NaClO3/HCl in aqueous acetic acid to

chlorinate activated arenes and α-position of ketones.

The earlier system has limitations of use of acetic acid as solvent, poor selectivity,

low yield and long reaction time (20 h). However, our present method is free from use

of organic solvent, have low reaction time (upto 3 h) and good yield (75-96%) of

chlorinated product (Figure I).

R2

R1NaCLO3 - HCl

H2O, r.t.

R1

R2

Cl(n)

R1 = OH, NH2, NHCOMe, NHCOPh, CHO, COOH, CN

R2 = H, OH, Cl, Br, NO2

Figure 1.1. Oxidative chlorination of aromatic substrates in water

Chlorination is an important reaction of organic chemistry because of wide variety of

uses of chloro-substituted organic compounds in fine chemicals and pharmaceutical

intermediates. Therefore, large number of methods are available in the prior art for

chlorination of organic compounds.

However, most of these methods involved the use of organic solvents which have

serious environmental impacts and also having disadvantages of long duration, high

temperature and use of catalyst, so there is need for the development of a method

which is efficient, free from organic solvent, cost effective and easy to handle.

Also, one of the key principles of green chemistry is the elimination of solvent in

chemical processes or the replacement of hazardous solvent with environmentally-

benign solvents.

Introduction

Water is the most promising solvent because it is readily available, non-flammable,

non-toxic and could offer the easy separation of reagents or catalysts from many

organic products. Therefore, in our present study, a method has been developed for

the chlorination of aromatic compounds using NaClO3/HCl in aqueous medium.

The present system uses the water as reaction media and also provides the chlorinated

aromatic products in good to high yields (75-96%) under the mild conditions. Also,

this system is cost effective, efficient and easy to handle.

2. General procedure for the chlorination of aromatic compounds

2.1 Monochlorination:

An aqueous solution of NaClO3 (0.005 mol) in water (8-10 Ml) was added to a fine

powder of aromatic substrate (0.01 mol) taken in a 10-0 ml round-bottom flask

equipped with a magnetic stirring bar at room temperature. After that HCl (2 ml) was

added dropwise for 15 minutes. The reaction completion was monitored with thin

layer chromatography (TLC). After completion of the reaction, 5 ml of water was

added to separate the product; product was filtered, and dried in oven. The structures

of products were confirmed by 1H NMR, mass spectra and were compared with

authentic samples.

Introduction

Alkyl Halide

R - X (X = F, Cl, Br, I)

Halogen bonded to sp3 carbon

Methyl Primary Secondary Tertiary

CH3X RCH2X CH - XR

R

R

RC

X

R

Common Names: Generally two words

CH2X

Benzyl Halide, i.e, X = Cl, - benzyl chloride

C=C

H

H

H

CH2X

Allyl Halide, i.e, X = Br, - allyl bromide

CR

R

R

X

Alkyl Halide, i.e., X = CH3, X = I - t-butyl iodide

IUPAC Nomenclature

1. Find longest chain, if double or triple bonds present the Present

chain must contain it.

2. Number the chain so as to give lowest series of substituent numbers.Treat the halogens just as if they were allyl branches standard rules apply.

Br

4-bromo-2,3-dimethylhexane

Br

Br

3-bromo-2-(1-bromoethyl)-4,5-dimethyl-1-hexane

Introduction

C X

H a lo g e n B o n d le n g t h ( A .)B o n d S tr e n g th

(k c a l .m o l)D ip o le M o m e n t ( D )

FC l

B r

I 2 .1 4

1 .9 31 .7 8

1 .3 9 1 0 9

8 4

7 0

5 6

1 .8 2

1 .9 4

1 .7 9

1 .6 4

Electrophilic site : Electron Defficient

A lk y l H a l id e S t ru c tu re

F re e ra d ic a l H a lo g e n a t io n o f A lk a n e s

H 3 C - CH 3 + X 2

h e a t o r

l ig h tH 3 C - CH 2 - HX

X

X = Cl, Br, I

M a r k o v n ik o v A d d it io n o f H X to A lk e n e s

+ HX

H R

HH

XR

X = Cl, Br, I

V ic in a l D ih a lo g e n a t io n o f A lk e n e s

+ X 2

H R

HX

XR

X = Cl, Br

Trans stereochemistry

A n t i -M a rk o v n ik o v A d d it io n o f H B r to A lk e n e s

+ HBr

H

B rH

HR

R

Peroxides

Introduction

Free radical chlorination or propane leads to two isomeric products.

H - C - C - C -H

H H. H

H H. H

Cl2

∆H - C - C - C -H

H H. H

H. ClH

+ H - C - C - C -H

H H H

Cl HH

1-Chloropropane (30%) 2-Chloropropane (70%)

H, 6 - 1. Hydrogen

H, 2 - 2. Hydrogen

Abstraction of

1. Hydrogen

Abstraction of

2. Hydrogen

Statistical factors: There is six 1. hydrogens and two 2

. hydrogens, if the amount

of product formed depended only on the likelyhood of a particular type of hydrogenbeing abstracted by a chlorine radical the product ratio should be 3 primary and

1 secondary.

But

The actual product ratio is 1 primary (30% of all product formed) to 2. secondary

(70% of all product formed). clearly some other factor is affecting the rate of

hydrogen abstraction from propane.

Consider the Enthalpies of Reaction (∆Η∆Η∆Η∆Η ....) for H abstraction

Primary Abstraction

H3C - CH 2 - CH 3 - Cl. H3C - CH 2 - CH 2 + HCl

∆Η.... = + 101 Κ cal/mol

Secondary Abstraction

H3C - CH 2 - CH 3 - Cl.

H3C - .CH - CH 3 + HCl

∆Η.... = + 98 Κ cal/mol

More 2. product forms because the 2. Radical is more stable

Ene

rgy The secondary radical is 3 kcal/mol more stable than the

primary radical (due to hyperconjugation) and is more likely to be abstracted by the chlorine radical.

This result in more of the 2-chloropropane product being formed.

H3C - CH 2 - CH 3

H3C - CH 2 - CH 2.

H3C - .CH - CH 3

3kcal/mol

Reactivity of 1. vs 2

. Hydrogens

Introduction

2.2 Dichlorination

Process for the synthesis of dichlorinated product was same as that given in

monochlorination, except 0.01 mol of NaClO3 and 4 ml of HCl was used wrt 0.01 mol

of substrate.

Examples:

In below results, the chlorination was first tried on 4-chloroacetanilide by using

NaClO3 (0.01 mol), NaCl (0.03 mol) and H2SO4 (1 mL) in water (Table 1.1, Entry 1).

The chlorinating reagent is thus generated in-situ in the reaction mixture by oxidizing

NaCl using NaClO3 as an oxidizing agent in acidic medium.

Introduction

Table 1.1 Screening of existing optimum reaction conditions for oxychlorination using different reagent systems in aqueous media.

Entry Reagent System Reaction Conditions Starting Material Product Yielda (%)

1. NaCl/NaClO3/ H2SO4

b 2 h at r.t. NHCOCH3Cl

NHCOCH3Cl

Cl

87

2. HCl/NaClO3c 2 h at r.t. NHCOCH3Cl

NHCOCH3Cl

Cl

95

3. HCl/NaIO4d 4 h at r.t. NHCOCH3Cl

NHCOCH3Cl

Cl

16

4. HCl/H2O2e 4 h at r.t. NHCOCH3Cl

NHCOCH3Cl

Cl

22

5. HCl/ NaBO3.3H2O

t 4 h at r.t. NHCOCH3Cl

-------

---

a Isolated yields b Conditions: Substrate, 0.01 mol;NaCl, 0.03 mol; NaClO3, 0.005 mol; H2SO4, 1 Ml;H2O, 8Ml c Conditions: Substrate, 0.01 mol;NaClO3, 0.005 mol; HCl, 2 Ml;H2O, 8Ml d Conditions: Substrate, 0.01 mol;NalO4, 0.005 mol; HCl, 2 Ml;H2O, 8Ml e Conditions: Substrate, 0.01 mol;HCl.2Ml;H2O2, 3Ml; H2O.8Ml f Conditions: Substrate, 0.01 mol;NaBO3.3H2O,0.01 mol; HCl, 2 Ml; H2O, 8 ML

Introduction

Later on, HCl was tried instead of NaCl and H2SO4, which acts as a chlorine source as

well makes the reaction mixture acidic ( Table 1.1, Entry 2). Results of table 1 show

that the chlorinated product obtained in better yield when HCl was used in place of

NaCl and H2SO4. Chlorination was also tried in water bu using various oxidants such

as sodium periodate. H2O2 (30%) and sodium perborate (Table 1.1).

The results suggest that very little amount of product is formed in case of NaIO4

(13%) and H2O2 (21%) and no product was formed with sodium perborate. Therefore,

it is found experimentally that sodium chlorate and HCl gave the best results in

aqueous medium.

2.3 Effect of surfactant:

Ionic and non ionic surfactants were used to study the effect of surfactant on the yield

and reaction time. It was observed that surfactant improves the distersion of aromatic

substrates in water and also improves the texture of product but there was no effect on

yield and reaction time.

Introduction

Allylic PositionCarbons bonded to double bonds are called allylic carbons. The hydrogens bonded to allylic carbons are allylic hydrogens.

Allylic Hydrogens

C

C

H H

H H

Allylic carbons C

HH

Allylic carbon

Allylic Hydrohens

The Allylic position has a special reactivity

C

Allylic Bromination with NBS

NBS

CCl4 + ∆HH

C

H Br

N-Br

Very weak N-Br bond

NBS - N - Bromosuccinimide

Allylic Bromination is a free radical chain reaction

Initiation

N-Br∆

N .

O

O

+ Br -Cleavage of weak N - Br bond gives the

NBS radical which is the chain carrier.

C

HH

Propagation

+ N .

O

O

+ N-H

O

O

Allylic hydrogen abstraction leadsto formation of resonance stabilizedallylic radical.

H+ Br-N

O

O

+O

O

.NH Br

PRODUCT

Allylic redical abstraction brom ine atom from NBS forms product and chain carrying NBS radical

Allylic Bromination

Introduction

2.4 Effect of concentration of HCl

The amount of HCl from 2 ml to 1.5 ml, the yield of 2, 4-dichloroacetanilide get

decreased upto 70%. Also, depression in melting point reveals that underchlorinated

product was formed due to decrease in the amount of HCl. On further decreasing the

amount of HCl from 1.5 ml to 1 ml, no product was obtained.

It was observed that the yield and menting point of 2.4-dichloroacetanilide became

stagnant on increasing the amount of HCl from 2 ml to 2.4 ml. hence, the ideal

amount of HCl is 2 ml.

2.5 Effect of concentration of NaCIO3

Decreasing in sodium chlorate (NaCIO3) concentration from 0.005 mol to 0.0033 mol

resulted in decrease of the yield of 2, 4-dichloroacetanilide.

Melting point of product was also not within the desired range due to

underchlorination of 4-chloroacetanilide in the presence of 0.0033 mol of NaCIO3.

While increasing the concentration of NaCIO3 from 0.005 to 0.015 mol, there was no

effect on these both parameters.

Therefore, it was concluded experimentally that 2 Ml of HCl and 0.005 mol of

NaCIO3 afforded the best yield of chlorinated product. The dichlorination can also be

performed by increasing the amount of HCl along with the amount of NaCIO3.

To show the general application of the method, it was applied to a variety of aromatic

compounds to give corresponding chlorinated products in good yields. The results of

this investigation are tabulated in table 2.

It is evident from the results that all aromatic substrates were chlorinated within 1.5-

3.0 h in good yields. 2,4-dichloroacetanilide (Table 1.2, Entry 1) was obtained in best

yield (95%) from 4-chloroacetanilide within 2 h at room temperature and having an

HPLC purity of 96.8% (Table 1.3, Entry 1). 4-Nitroacetanilide showed no reactivity

up to 4 h at room temperature (25˚C) while at slightly higher temperature (45˚C), 2-

chloro-4-nitroacetanilide was obtained in good yield (75%) within 3 h of reaction

(Table 1.2, Entry 3,4).

Introduction

Earlier Jerzy et al. has synthesized 2-chloro-4-nitroacetanilide from 4-nitroacetanilide

in poor yield (32%) along with fornation of 2,6-dichloro-4-nitroacetanilide (68%) at

50˚C.3-chloro-4-hydroxybenzaldehyde which is used as an intermediate in organic

syntheses was obtained in 86% yield (Table 1.1, Entry 13) with an HPLC purity of

98.38%. 5-chlorosalicylic acid (Table 1.1, Entry 14) which is used as intermediate of

pesticide, medicine and dyes was obtained in 82% within 1.5 h at room temperature

from salicylic acid.

This compound was also synthesized by H.A.Muathen using SnCl4/Pb(OAc)4 in ethyl

acetate in 77% yield.

Table 1.2 Existing approaches of oxidative chlorination of aromatic compounds in

aqueous medium.

R1 R1

R2 R2

Cl(n)

NaClO 3 - HCl

H2O, r.t.

Entry Starting Material

Reaction Conditions

Product Yielda (%)

Mp °C (lit.)

1.

NHCONH3Cl

2 h, r.t.

NHCONH3Cl

Cl

95b 145(143-

146)

2. NHCONH3Br

2 h, r.t. NHCONH 3

Cl

Br

93b 152(151-

152)

3. OH CHO

4 h, r.t. OH CHO

Cl

82b 130(128-

132)

4. COOH

OH

2 h, r.t. COOH

OH

Cl

Cl

83c 222(221-

224)

Continued to next page…………

Introduction

5.

NH2O2N

2 h, r.t. NH2O2N

Cl

90b 107(107-

110)

6. OH

NO2

2 h, r.t. OH

NO2

Cl

84b 83(85-

87)

7. NHCOPh

3 h, r.t. -------- Complex

Mixture ---

8.. NHCOPh

1.5h, r.t. NHCOPhCl

93b

190(192-

193)

9. CHO

OH

1.5h, r.t. CHO

OH

Cl

85b 100(99-

103)

10. COOHOH

1.5h, r.t. COOHOH

Cl

82b 166(168-

170)

11. NHCOCH3O2N

4 h, r.t. ---- --- ---

12. O2N NHCOCH3

3 h, 45 °C O2N NHCOCH3

Cl

75b 138(138-

139)

13. COOHOH

4 h, r.t. COOHOH

Cl

Cl

86c 264(264-

266)

14. CNOH

1.5h, r.t. CNOH

Cl

82b 149(150)

a Isolated yields b Monochlorination: Substrate, 0.01 mol; NaClO3, 0.005 mol; HCl, 2mL; H2O, 8-10 ml. c Dichlorination: Substrate, 0.01 mol; NaCLO3, 0.01 mol; HCl, 4mL; H2O, 8-10ml.

Table 1.2 (Continued )

Introduction

In case of benzanilide, a mixture of substrate and product (underchlorinated product)

was formed at room temperature within 3 h (Table 1.1, Entry 7) but at slightly higher

temperature (40˚C), para-substituted product was obtained within 1.5 h (Table 1.1

Entry 8) with an HPLC purity of 95.23% which is an industrially-important

compound.

However, substituted anilines and phenols can be chlorinated at 25ο C in a very good

product yield

Table 1.3 Selectivity of products in the chlorination of various existing aromatic

substrates

Entry Substrate Product Yielda

(%)

Product Purity b (%) Main

Product Others

1. NHCONH3Cl

NHCONH3Cl

Cl

97 96.90 3.10

2. COOHOH

COOHOH

Cl

83 98.30 1.70

3. CNOH

CNOH

Cl

85 98.50 1.50

4. NHCOPh

NHCOPhCl

93 97 3.00

5. NHCOCH3Br

NHCOCH3Br

Cl

95 96.35 3.65

6. CHOOH

CHOOH

Cl

82 98.20 1.80

a Isolated yield b Purity determined by HPLC

Introduction

Encouraged by the results/findings of activated arenes, same system, i.e.,NaCIO3/HCl

using H2O as reaction media was also tried for the chlorination of deactivated arenes

such as benzoic acid and nitrobenzene. However, the present system failed to

chlorinate the deactivated aromatic compounds at 60˚C and 80˚C even after 20 h.

Therefore, this system can be utilized in commercial operations to chlorinate activated

arenes in good yield and under mild conditions.

It is evident from literature that in case of oxychlorination it is possible to oxidize the

chloride under acidic conditions to obtain HOCl and/or Cl2; these oxidized species

then reacts in-situ with substrates such as arenes to yield chlorinated product.

Therefore, under certain conditions either Cl2 or HOCl can be main chlorinating

agents or both can act concurrently to yield chlorinated product. However, it has been

reported recently that at very low pH (Ph < 3) Cl2 serves as an active chlorinating

agent while at higher pH (3-6.5) HOCl is the active chlorinating species.

Cl2 + H2O HOCl + H+ + Cl

-at pH 3 - 6.5

at pH <3

The PH of our reaction medium is very low (PH < 1) so the active chlorinating species

may be Cl2 rather than HOCl. Also, from rate data and relative reactivities studies it

has been identified that Cl2 is much more reactive chlorinating agent than HOCl and

addition of large amount of acid or lowering the Ph of the reaction will suppress the

hydrolysis of Cl2 to HOCl (eq.1).

Therefore, it can be concluded that NaClO3 will oxidize the chloride to form chlorine

and due to higher reactivity of Cl2 it will serve as an active chlorinating species which

furnishes the Cl+ ion to accomplish a rapid chlorination of substrates (Scheme 2).

Theoretically, one equivalent of chlorate generates three equivalents of chlorinating

agent; however, this was not accorded precisely by experimental results.

………..Eq. (1)

Introduction

NaClO3 + 6HCl 3Cl2 + NaCl + 3H2O

R1

+ Cl+ -------- Cl-

R1

Cl

R2R2

Fig. 1.2 Plausible Mechanism of Oxidative Chlorination

Previous studies of organic transformation shows, organic ammonium bromides are

becoming a small yet important group of reagents. Because of their ease of formation,

mildness, immense versatility, these reagents have become quite popular and a

number of reports are available discussing the importance of these reagents in various

types of transformations.

The effects of pH, electrolyte, and surface preparation on the surface excess and

adsorption kinetics are reported. At all other concentrations and even at the Critical

Surface Aggregation Concentration when electrolyte is present, the adsorption is

complete within minutes.

Halogenated organic compounds form an important class of intermediates as

they can be converted efficiently into other functionality by simple chemical

transformations.

The manufacture of a range of bulk and fine chemicals including flame

retardants, disinfectants and antibacterial and antiviral drugs, involve

bromination. Bromoaromatics are widely used as intermediates in the

manufacture of pharmaceuticals, agrochemicals and other speciality

chemical products.

Selective bromination of aromatic compounds is investigated in view of the

importance of the brominated compounds in organic synthesis. Consequently,

Introduction

a variety of methods for the bromination of aromatics have been reported in

the literature.

Brominated aromatic compounds are widely used as building blocks for

pharmaceuticals, and other specialty chemicals. Most of the aromatic compounds are

poorly soluble in water, and this has been a major limitation in the preparation of

industrially-important brominated compounds under aqueous conditions.

Classical nuclear bromination of aromatic compounds involves the use of: (a)

Bromine; (b) A catalyst like FeCl3, FeBr3, iodine, thallium acetate etc; (c) Absence of

light, often yielding undesired Co-products. The direct bromination of an aromatic

system presents an environmental problem in large-scale operations. Besides, the

bromination is wasteful as one half ends up as hydrogen bromide and this renders the

process more expensive. Oxybromination using HBr is highly toxic and corrosive and

is as harmful as molecular bromine to the environment.

Cerichelli et al. studied the bromination of anilines in aqueous suspension of 1-

hexadecylpyridinium tribromide (CPyBr3). The drawbacks include an additional step

for the formation of tribromide reagent prior to bromination, complex workup

procedure in which brominated product was extracted using diethyl ether and that

molecular bromine is required for the preparation of tribromide.

Currie et al. have performed the bromination of phenols and anilines in a

dodecyltrimethylammonium bromide (DTAB) based microemulsion. The process

uses excess amount of hazardous HNO3 and volatile halogenated organic solvent

(CH2Cl2). Firouzabadi et al. have disclosed a double catalytic system for the

bromination of phenol derivatives using Br2/Cetyltrimethylammonium bromide

(CTAB)/Tungstophosphoric acid cesium salt (Cs2.5H0.5PW12O40) reagent system.

The drawbacks are the use of excess amount of reagent (Br2: substrate, 1.1:1 for

mono- and 2.2:1 for dibromination) and expensive tungstophoric acid cesium salt.

Also, filtration abd evaporation of the excess amount of halogenated volatile organic

solvent is cumbersome during large scale operations.

Introduction

The reported methods on bromination of aromatic compounds in water are rare and

limited to only few examples such as NaBr-H2O2/scCO2 biphasic system and H2O2-

HBr/”on water” system, albeit low conversions, high temperature (40 ˚C) and a very

long reaction time (from 8 h to 28 h) ) are some of the concomitant shortcomings.

There are also some other reagents that have been developed as a substitute for Br2,

including, but not limited to, N-bromosuccinimide/I-butyl-3-methylimidazolium

bromide, ZrBr4/diazene, [K. 18-crown-6] Br3, 1-butyl-3-methylpyridinium tribromide

[BMPy] Br3, 3-methylimidazolium tribromide [Hmim] Br3, 1-butyl-3-

methylimidazolium tribromide [Bmim] Br3 pentylpyridinium tribromide, ethylene

bis(N-methylimidazolium) ditribromide.

However, no such reagent is commercialized to date, because of their expensive

nature, poor recovery and recycling of spent reagent, disposal of large amounts of

HBr waste and that the reagents are also not so stable and weaken during long periods

of storage, hence thay are meant only for laboratory-scale preparations with limited

applications. Preparation of all these reagents involve liquid bromine at some stage,

thereby, increases the cost of the end-product.

All the above reported methods suffer from using not easily available compounds and

others use highly-corrosive or expensive reagents and toxic organic solvents.

Examples are: Br2/Ag2SO4, Br2/SbF3/HF, Br2/SO2Cl2/Zeolite, Br2/Zeolite, Br2/H2O2,

Br2/H2O2/Layered Double Hydroxide-WO4, Br2/tetrabutylammonium

peroxydisulphate etc.

Therefore, the bromination reaction has been still attracting attention to develop the

more practical method suitable for industrial-scale synthesis. These observations

enhance the versatility of bromine as an inexpensive, readily available starting

material. A wide range of solvents have been employed in these reaction including,

carbon tetrachloride, hexane, methanol, acetonitrile, and acetic acid.

Introduction

Figure. 1.3 Ammonium bromide catalyzed oxibromination of aromatic compounds in

water using molecular Br2

NH4Br + Br2 NH4Br3 + Br•

X

Y NH4Br, Br2

10 - 20 min, 25

0C

Yield 91-99%

X

Y

Br (n)

X = OH, NH2, NHCOMe, NHCOPh, CHO, COOH

Y = H, OH, NO2, SO2, NH2

The processes of halogenation also vary according to the functional groups. These

include free radical halogenation, ketone halogenation, electrophilic halogenation and

addition halogenation reaction.

There are various processes for the halogenation of various organic compounds such

as free radical halogenation which is mainly done for the saturated hydrocarbons as

they do not add halogens, ketone halogenation, halogen addition reaction which is

used for alkenes and alkynes and electrophilic halogenation which is mainly used for

aromatic compounds.

In all these reaction, the determining factors are the type of functional groups of the

organic compounds. The other most important element of halogenation reactions is

type of halogens used. Saturated hydrocarbons typically do not add halogens but

undergo free radical halogenation, involving substitution of hydrogen atoms by

halogen. Fluorine and chlorine are most aggressive and electronegative halogenating

agents thereby react readily while bromine is a weakest one hence is least reactive

halogenating agent.

Introduction

On contrast the dehydrohalogenation of these halogenating agents follow a reverse

trend has been reported in case of iodine is most easily removed element from

organic, Organochlorine and organofluorine compounds are highly stable.

Bromination and iodination are more likely to substitute at the beta carbon2-4.

There are several facts which are applied for every halogen these are as follows.

3. Halogens Facts:

a. Halogens include chlorine, fluorine, bromine, iodine.

b. These are seven electrons in there outer orbits of all these halogens which

means that they are monovalent.

c. The boiling and melting point are lower than the other non-halogens and Non-

metals.

d. All halogens are poor conductors of electricity and heat.

e. All the halogen except elemental fluorine can expand their shell to include

valence electrons. They can hold around fourteen valence electrons in their

outer shell.

3.1 Properties of halogens:

While moving down in the group of halogens in the periodic table, (1.4). The

halogens shows a series of trends for instance, decrease in the electronegativity and

reactivity, increases the melting and boiling points.

Introduction

Table 1.4: Periodic properties of halogens

Halogen Standard At.Wt. (g/mol)

Melting Point (K)

Electronegativity (Pauling Scale)

Boiling

Point (K)

Chlorine 35.453 171.60 3.16 239.11

Bromine 79.904 265.8 2.96 332

Iodine 126.904 386.85 2.66 457.40

Fluorine 18.998 53.53 3.98 85.03

3.2 Reactivity

Generally, halogens are highly reactive agents, very unsafe to biological organisms

and environment if used in sufficient quantities. This high reactivity is mainly due to

atoms characteristics of being highly electronegative because of high effective nuclear

charge.

Among all halogens, fluorine is one of the most reactive elements which can ever

attack the inert molecules like glass as well as react and forms compounds with the

heavier noble gases. It is a very toxic and highly corrosive gas. The reactivity of

fluorine is so high that if it is used or stored in laboratory glassware even it can also

react with glass in the presence of even small amounts of water and form silicon tetra

fluoride (SiF4).

During process fluorine must be controlled with substances such as Teflon (an

organofluorine compound), clean and dry glassware, and metal such as Cu which

form a protecting coating of fluoride on their surface. Chlorine and bromine react

with most of the elements less vigoursly than does fluorine.

The chlorine and bromine both are used as disinfectants they kill bacteria and other

micro-organism through the process of sterilization, hence both are used for drinking

Introduction

water, for swimming pools, fresh wounds, spas, washing of dishes, and surfaces. The

process of bleaching of the fabric also utilizes the reactivity of chlorine.

Sodium hypochlorite, effective bleach for fabric is produced from the chlorine, there

easiest other chlorine-derived bleaches which are used for production of some paper

and paper products industries. Chlorine, in reaction with sodium from common salt

which is the inseparable part of the food and used widely at industrial scale.

In contrast to chlorine, iodine is less reactive and requires activation. It does not

combine with other elements easily such as sulphur and selenium. It can be concluded

that some halogens are highly reactive and can be potentially dangerous in many

reactions hence these must be handle with extra care during reaction processes,

however the halogens with less reactivity may produce desired products so do not

require much attention while handling.

3.3 Oxidizing power

Halogens act as oxidizing agents. The strength of an oxidizing agent depends on

several energy factors. Among the halogens, fluorine is the strongest oxidizing agent

and it will replace Cl- ions both in solution and in dry conditions. Similarly, chlorine

will replace the bromide in solution.

In general, any halogens of low atomic number will oxidize halogens of higher

atomic number. Halogenation reactions using chlorine, bromine, and iodine elements

are considered to be very importance. Halogenation specifically fluorination using

elemental fluorine is generally not suitable for direct halogenation reactions.

4. Type of Halogenation:

There are two types of reactions which are possible with these halogenating elements.

These include substitution halogenation and addition halogenation.

Introduction

4.1 Substitution Halogenation:

Substitution halogenation is the reaction in which an atom, often a hydrogen atom or

group of atoms which are usually functional groups, are substituted by the halogen

atom i.e; achlorination reaction of great importance involves the substitution of a

hydrogen atom from the methane by chlorine atom.

4.1.1 Aromatic Substitution:

The reaction between aromatic compound such as benzene and bromine in the

presence of aluminum chloride that results in formation of bromobenzene is an

example of aromatic substitution. It is an electrophilic substitution reaction. The

mechanism of which is formally a two-step process: (1) Lewis-base-Lewis acid

reaction between benzene and Br+, followed by (2) an E1 reaction that results in loss

of proton to regenerate the aromatic benzene ring.

4.2 Addition Halogenation:

This reaction generally takes place with unsaturated hydrocarbons. In this the

halogenating elements are attached with the hydrocarbons. Chlorine, bromine, and

iodine readily react with most olefins. The reaction between ethylene and Chlorine

that form 1, 2-dichloroethane is of great commercial importance as the formed

compound is used for the manufacturing of vinyl chloride. To measure quantitatively

the numbers of CH (or ethylenic-type) and bond in organic compounds, these

addition reactions with bromine or iodine are frequently used.

Numbers of bromine or values of iodine are the important measures of the degree of

unsaturation of the hydrocarbons. Substitution halogenations for aromatic

compounds are made through ionic reactions, while the chlorination reactions using

elemental chlorine is similar to the reaction used for addition chlorination of olefins.

4.2.1 Oxyhalogenation

There is a very important role of halogenated organic compounds organic chemistry

as well as in commercial processes. They are important as starting substrates as well as

Introduction

versatile intermediate in the organic synthesis. Halogenation in laboratory

syntheses involves hazards, toxic and corrosive molecular halogens and further these

reactions required chlorinated solvents.

Therefore direct use of halonium species in the reactions is no more recommendable

and alternative strategy is required for their use. Naturally electrophilic halogenation

takes place through oxidative halogenation with the exception of fluorination as it is

difficult to oxidize fluorine.

Naturally found halo peroxidases marine source are algae’s which synthesize halo

peroxidases which is a very effective oxidant enzyme for halides. By using other

reactant H2O2.The efficiency and rate of conversion for phenol with different reagents

were studied and reported.

The better approach could be an in-situ generation of halonium class via the oxidation

of halides using appropriate oxidants under moderate reaction conditions to overcome

the current drawbacks.

An increasing environmental concerns and advanced studies on oxidative

halogenations, it is desirable for synthetic chemists to study and understand in-depth

the oxidative halogenations. Hence efforts are being made for development of

sustainable oxyhalogenation. During present thesis work using greener reagents.

Introduction

The halogens and other halogenating reagents are employed for the purpose of

oxyhalogenation.Though halogenation covers diverse areas; the present work is

pertaining to the bromination and chlorination of industrially-important aromatic

compounds.

5. Bromination as commercial process

Bromination of aromat ic compounds specially of aromatics has catched a

considerable amount of attention during recent years because of its significant

commercial importance as compound produced through it acts as potent antitumor,

antibacterial, antifungal antineoplastic, antiviral and antioxidizing agents and and also

act as industrial intermediates for the manufacturing of of pure chemicals,

pharmaceuticals, and agrochemicals.

Unfortunately, there are many hazards accompanying with the traditional bromination

processes and these cannot be ignored.

There are growing concerns about the environmental problems caused by the use of

these detrimental chemicals and solvents in traditional bromination and on the

anticipated legislation against their use.

Consequently, there is a great need for the methodology that would be ecologically-

safe and clean on one hand and very efficient, site selective, operationally simple and

easy, and cost-effective. Selective bromination of aromatics which is of great

commercial importance has been a focus point.

5.1 Brominated Organic Compounds

In brominated organic compounds, bromine which can attached to carbon,

nitrogen and oxygen (very rarely) by covalent bond, is a very important group of

organic halogen compounds. There is nearly approx. fifteen hundred compounds

naturally occurring bromine containing organic compounds produced by marine and

industrial plants, bacteria, fungi, insects, marine animals, etc.

However, far more important are synthetic organic compounds. Organic bromine

compounds are the predominant industrial bromine compounds that account for

Introduction

approximately 80 percent of bromine production in terms of bromine consumption.

Mainly, there are two categories of industrially produced organic bromine

compounds.

a) Organic bromine compounds are the largest segment in terms of consumed

volume. In these brominated compounds, the bromine atom is retained in the

final molecular structure, and its presence contributes to the properties of

the desired final products.

These include gasoline additives, biocides, halons, flame retardants, pharmaceuticals,

bromobutyl rubber, dyes, and agrochemicals etc. Among these some products like

ethylene dibromide, halons, and methyl bromide are consumed less than others as

they are subjected to environmental restrictions,16 but rest of the products specially

flame retardants and biocides are much in demand and the overall market of the

segment is still forecast to be grown wider.

b) Traditionally and commercially these brominated organic compounds played

a very important role as an intermediate in the production of agrochemicals,

pharmaceuticals and dyes, however new process development resulted in the

new applications of these brominated compounds like in UV sunscreens, high

performance polymers, and many more and it has been forecast that this

segment will be wider in their uses. The global consumption of Br2 as

intermediate is dwarfed by the analogous consumption of Cl2.

The scope of present research work is narrow to organic brominated compounds

having large industrial scope.

5.2 Industrial-Importance of Some Brominated Compounds

The aromatic bromine compounds find industrial applications in many ways:

• P- Bromoaniline is used in the preparation of azo dyes.

• P- Bromophenol is used as disinfectant.

• 2, 4, 6- Tribromophenol used as an intermediate for the formation of flame

Introduction

retardants, in manufacture of selective fungicide, germicide, and fire

extinguishing fluids.

• P- Bromoacetanilide is used as analgesic, antipyretic.

• 2-Bromo-4-nitroacetanilide is used as drug intermediate, in preparation of

Nimenslide.

• 3-Bromo-4-fluoronitrobenzene is a potential intermediate for ciprofloxacin

and other antibiotic drugs.

• 2, 4, 6-Tribromo-3-nitroaniline is a precursor for the nthesis of

substituted thiazoles which are used as fungicides.

• Bromobenzene is used as a motor oil additive and bromonaphthalene is

used in spectroscopy and refractometry.

• 4, 4‘-isopropylidine- bis-(2, 6-dibromophenol) which is commonly known as

Tetrabromobisphenol -A (TBBPA) is a specialty chemical that has a wide

range of applications in the industries. It is used as a reactive flame retardant

in epoxy, vinyl esters, polystyrenes, phenolic resins, and polycarbonate resins.

TBBPA may be used as parent compound for the production of other flame

retardants. The importance of TBBPA can be understood by the fact that it is

one of the most widely used and largest selling brominated flame-retardant

globally. It is used broadly to deliver flame retardancy for styrenic

thermoplastics and for some thermoset resins. TBBPA is fully ecologically sfe

and fulfills all legislations for recycling and recovery.

• 2, 6-Dibromo-4-nitroaniline [Br2C6H2(NO2)NH2] is a potent antifungal and

also useful in the synthesis of diazonium salts t h a t are helping in the

production of aligomeric disperse dyes.

• 3, 5-Dibromosalicylaldehyde serves as an inhibitor of stearoyl-CoA

desaturase, in pharmaceutical industry, obesity is being trated by using this

specify chemical.

Introduction

• 5-Bromovanillin is used in pharmaceutical flavor, agrochemical, and organic

synthesis industries.

• 2-Fluoroaniline is useful inter-alia in the preparation of pharmaceuticals

and agrochemicals.

• Quaternary ammonium tribromides used as a vital reagents for preparation of

bromoorganics which have antiviral, antineoplastic, anti-inflammatory and

antifungal properties and are also capable to use as flame retardant.

6. Chlorination (FACTS method)

The chlorination of organic aromatic compounds considered to be a very important

synthetic method as these produced chloro-substituted organic materials which are the

main contributing intermediates for the production of a range of various fine

chemicals, agrochemicals and pharmaceuticals.

Therefore, many methods have been developed for chlorination those are available in

literature. Many traditional methods which are used to insert chlorine atom into

organic substrates, whether i t i s d on e th ro u gh free-redical processes or

through polar addition to olefinic groups or through electrophilic substitution on

aromatic ones.

All these involves the use of potentially hazards, difficult to store and handle

elemental chlorine that is gases at room temperature and 1 atm of pressure or it may

have high vopour pressure.

The range of FACTS method has its oun determination limitations from 0.1-10 mg/L

molecular chlorine. The analytical part adapted the total chlorine determination of

available oxidants and total chlorine.

Introduction

In addition, combination systems based on mixture of diverse oxidants, i.e., perchloric

acid, manganese (III) acetate, H2O2 , LDA, oxane and dimethyl suphoxide, with

chlorine sources have been developed to generate chlorine.

Most of reactions of chlorination fall into four general categories, viz.

I. Reaction of electron-rich aromatic rings with molecular chlorine.

II. Reaction of aromatic compounds with systems which furnish a positively

charged chlorine species.

III. Direct chlorination of an aromatic molecule with chlorine, apparently derived

from metal halide or, but without the addition of any free chlorine; e.g.

Introduction

HOCl + H2O Cl2 + H2O

ArCl + Cl2 ArCl + HCl

IV. Reaction of less-activated rings with molecular chlorine in presence of a

catalyst.

Although, all the methods mentioned above in the prior art are known to be useful

for the chlorination of aromatic substrates, they have following drawbacks:

• Some of methods described in prior art involve high temperature reactions,

which are difficult to handle, and often leads to variety of side products.

• Transportation and handling of large quantity of molecular chlorine may lead

to further complications.

• Activated aromatics have been found to undergo polychlorinations rather

than monochlorination resulting in the mixture of isomers, which are difficult

to separate.

• The heterogeneous catalytic route involving the use of acidic zeolite as

catalyst also suffer from disadvantages like side chain chlorination, use of

inhibitors, etc.

• Many of reagents mentioned above in the prior art lead to radical

chlorination resulting in substitution in the side chain of arenes rather than

on ring, under the reaction conditions of higher temperature or irradiation

with UV Light

Analyzing these literature data, one can see the most promising examples of

chlorination of arenes include synthesis where chlorine is generated in situ in

presence of suitable oxidant.

Introduction

6.1 Industrial-Importance of Some Chlorinated Compounds

The chlorinated organic compounds find industrial applications in many ways:

• 3, 5-Dichloro-4-hydroxybenzonitrile is used as pesticide.

• 2-Chloro-4-methylphenol is a valuable intermediate for the preparation of

crop protection agents and pharmaceuticals.

• The chlorinated benzoates can be used as chemical intermediates to make

pharmaceuticals, agricultural chemicals and other products.

• Chlorobenzenes are useful as starting materials for Medicines and agricultural

chemicals.

• 2-Chlorobenzothiazole can be used as intermediate product for t h e

preparation of specific herbicides.

• The major use of p-chlorotoluene is in the manufacture of p-

chlorobenzotrifluoride, a key intermediate in dinitroaniline and diphenyl ether

herbicides.

• 4-Bromo-2-chloroacetanilide compound finds application as intermediate in

research and development.

• 2-Bromo-6-chloro-4-nitroaniline is used as a dye and intermediate for dyes.

• 5-Chloroisatin is used as intermediate for pharmaceuticals and agrochemicals.

• 5-Chlorosalicylic acid is used as intermediate of pharmaceutical, agro-

chemicals and dyes.

Introduction

7. Iodination

In traditional methods iodination normally approached by using Iodine. In special

cases when there is strong electron donating groups in the aromatic species, the

reaction with iodine occurs readily, however control over reactivity and selectivity of

the halogenating agents become difficult. In care of highly activated aromatic

systems such as phenols, the position and degree of iodination are difficult to control.

Thus, there is a challenge for the chemists those working on green process or towards

gree approach is very important to identify the correct combination of reactivity and

selectivity. Iodination can be complicated by the hydrogen iodine co-product while,

being the strongest of the halogen acids, can cause photolytic cleavage of

heteroaromatic rings.

This may be avoided by adding mercuric oxide, which removes the acid as it is

formed. I2/HIO3/HOAc, ICl and I2 in 50 percent aq. HOAc have been used in various

studies.

8. Motivation/Objective:

The major objectives of the present work are as follow:

I. Synthesis and characterization homogeneous catalyst for bromination

derivative of aromatics and analogues.

II. Oxidative chlorination of aromatic compounds in aqueous media using N-

Chlorosuccinimide.

III. Demonstration of yield dependency over the factors including catalyst

Concentration, solvent effect, electronic effect, purity of reactant etc.

IV. Synthesis of cetylpyridinium tribromide (CetPyTB) reagent by noble

synthetic route and bromination of organic compound using CetPyTB.

V. Bromination of organic compounds using AlBr3-Br2 as reagent in aq.media.

VI. Process development and technology transfer for important brominated

compounds. The motivation and research strategy is illustrated in scheme 1.

Introduction

Scheme 1: Schematic representation of work plan.

chapter - 1 using new reagent systems...

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