Title of Invention	A PROCESS FOR PREPARATION OF 5-CHLORO-2-(2,4-DICHLOROPHENOXY) ANILINE
Abstract	A novel process for the selective reduction of halonitroarenes in general and halonitroaromatic arenes in particular, without the hydrogenolysis of the C-CI (where, X represents F-, CI-, Br- and I) and the C-O-C bonds, in the presence of platinum based catalysts and ammonium formate. The invention makes the use of duel function of ammonium formate, as a hydrogen source for partial reduction (catalytic transfer hydrogenation) and as an additive controlling the hydrogenolysis side reactions during the completion of the reduction by high pressure catalytic hydrogenation using external hydrogen gas source. Uniqueness of the invention lies in the fact that either the catalytic transfer hydrogenation with ammonium formate or high pressure catalytic hydrogenation in the absence of ammonium formate, when used alone result in lower purity of the said amine. This invention -product is used to synthesize intermediates for making antibacterial compounds.

Title of Invention

A PROCESS FOR PREPARATION OF 5-CHLORO-2-(2,4-DICHLOROPHENOXY) ANILINE

Abstract

A novel process for the selective reduction of halonitroarenes in general and halonitroaromatic arenes in particular, without the hydrogenolysis of the C-CI (where, X represents F-, CI-, Br- and I) and the C-O-C bonds, in the presence of platinum based catalysts and ammonium formate. The invention makes the use of duel function of ammonium formate, as a hydrogen source for partial reduction (catalytic transfer hydrogenation) and as an additive controlling the hydrogenolysis side reactions during the completion of the reduction by high pressure catalytic hydrogenation using external hydrogen gas source. Uniqueness of the invention lies in the fact that either the catalytic transfer hydrogenation with ammonium formate or high pressure catalytic hydrogenation in the absence of ammonium formate, when used alone result in lower purity of the said amine. This invention -product is used to synthesize intermediates for making antibacterial compounds.

Full Text	FORM 2 THE PATENTS ACT 1970 (39 of 1970) & The Patent Rules, 2003 Provisional Specification (See section 10 and rule 13) A process for preparation of 5-chloro-2-(2,4-dichlorophenoxy)aniline Dorf Ketal Chemicals (I) Pvt. Ltd Dorf Ketal Tower, D'monte Street, Orlem, Malad (W), Mumbai, 400064 Maharashtra State, India An Indian company registered under the Companies Act, 1956 The following specification describes the invention: A process for preparation of 5-chloro-2-(2,4-dichlorophenoxy)aniline Field of invention The Invention relates to a process for the preparation of halogenated aromatic primary amines such as triclosan amine which is 5-chloro-2-(2,4-dichlorophenoxy)aniline, by catalytic hydrogenation of the corresponding halogenated aromatic nitro compounds in the presence of noble metal catalyst such platinum supported on carbon Discussion of prior art It is known that halogenated aromatic primary amines are obtained by catalytic hydrogenation of their corresponding halogenated aromatic nitro compounds. The hydrogenation additionally leads to dehalogenation thus to giving mixtures of dehalogenated and halogenated aromatic primary amines which are difficult to separate. The inventor of the present invention has performed several laboratory experiments to verify the conventional method used in reduction nitroether to form corresponding amine. The experimental details and results of one such experiment are presented in example 1 given below: EXAMPLE 1 Preparation of Triclosan amine The details given in Table 1, Table 2, and the procedural steps given below explain the method used for preparing Triclosan amine. Batch no: RM/IV/81 TABLE 1 Chemical name 5-chloro-2-(2,4-dichlorophenoxy)nitrobenzene 5-chloro-2-(2,4-dichlorophenoxy)aniline (Nitro ether) Purity = 99.36% (Amine) Mol wt 318.5 288.5 TABLE 2 Chemical name Weight (grams) 5-chloro-2-(2,4-dichlorophenoxy)nitrobenzene 131.3 g (solid content 80%) Iron powder 112.5 g (five lots of 22.5 g each) Acetic acid 6.1 g Water 125 g 5-chloro-2-(2,4-dichlorophenoxy)aniline(product) 79.2 g Procedure: Following steps were used in the experiment: (1) 131.3 gms of nitroether and 125 gms of water are taken in 4 necked round bottom flask equipped with stirrer, condenser, thermometer, and inlet for nitrogen gas. (2) To the above add first lot of iron powder and acetic acid in that order, as mentioned in table 2. (3) Heat the reaction mixture to 90 °C. (4) Add remaining lots of iron powder at interval of 30 minutes each. Frothing is observed during addition of iron powder. (5) . Maintain temperature at 90 C to 95 C and monitor the reaction (till absence of Nitro ether) by TLC/GC. ( Thin layer chromatography and gas chromatography) (6) Upon completion of reaction, add Toluene (150 g). (7) Reflux reaction mixture for 1 hour. (8) Cool to 55 to 60°C. (9) Filter reaction mass. (10) Wash Iron powder in the filter paper with hot additional Toluene (150 g). (11) Collect reaction mixture and washings of Iron powder. (12) Separate aqueous layer from toluene layer. (13) Toluene layer is washed with water (125 g). (14) Remove toluene by distillation. The purity of this amine is 99.39% (15) The above prepared amine that is 5-chloro-2-(2,4-dichlorophenoxy)aniline is used to make final product that is triclosan. (Instead of toluene, other solvents like chloroethylene also can be used.) Mole ratio = 5-chloro-2-(2, 4-dichlorophenoxy) nitrobenzene: Iron =1: 6.1 GC Purity = 99.39% (purity of amine) Yield=83.4% (yield of amine) The disadvantage of the above process are: 1 The iron powder has to be used in almost in the 1: 1 weight ratio of the amine. This lowers the output. 2 The recovered iron is not suitable for the next reaction and hence cannot be recycled. Hence disposal of this iron powder contaminated with the amine poses an environmental problem. 3 Amine is retained in the iron powder even after washings, hence there are losses. Hence there is a perceived necessity of finding alternative method to make 5-chloro-2-(2,4-dichlorophenoxy)aniline to overcome the above mentioned disadvantages and which will be economical and environmental friendly. Description of Invention Accordingly the steps used in the present invention are described below with reference to most preferred embodiment the invention. General procedure of the invention for the hydrogenation of nitroetherto Amine: 1. Nitroether, that is, 5-chloro-2-(2,4-dichlorophenoxy)nitrobenzene, methanol and the catalyst are charged to the autoclave which is then closed. 2. The autoclave is flushed with nitrogen three times to displace air followed by hydrogen three times. 3. The autoclave is then pressurized with hydrogen. 4. Agitation and heating is then started. 5. The reaction mass is maintained at the desired temperatures throughout the reaction by providing cooling if required. 6. After the reaction is complete, that is, there is no hydrogen uptake, the reaction mass is cooled. 7. The autoclave is vented and flushed with nitrogen three times. 8. The reaction mass is then filtered to separate the catalyst. The separated catalyst can be reused for subsequent reactions. 9. Methanol is distilled out along with water formed during the reaction. 10. Traces of water in the amine thus obtained are removed under reduced pressure at 120°C. The final amine is anlaysed by gas chromatography for purity. 11. The above prepared amine that is 5-chloro-2-(2,4-dichlorophenoxy)aniline is used to make final product that is triclosan The above mentioned procedural steps are used in conducting laboratory experiments, the details and results of which are given in example 2 EXAMPLE 2 The details of the ingredients used in the experiments and the results achieved therefrom are given below in Table 3 TABLE 3 Ingredients Expt No 1 Expt No2 Exptno3 Nitrocompound,5-chloro-2-(2,4dichlorophenoxy)nitrobenzene lOOgms lOOgms lOOgms Methanol lOOgms lOOgms lOOgms Catalyst Raney Nickel 5.0gms 5.0gms Pt/c 1.44gms Temperature 40 to 60 degc 105 degc 40-60 degc Pressure 25kgs lOkgs 25kgs Reaction Time 3.5hrs lOhrs 2.15 hrs GC analysis In% In% In% Product 5-chloro-2-(2,4-dichlorophenoxy)aniline 92.4475 93.3114 99.3514 Dehalogenated Produer 7.3783 5.1654 0.5750 Details of the catalysts used for the hydrogenation in these experiments are given below: Raney Ni: Monarch Catalysts Pvt. Ltd., KALCAT-8030 Lot # 092 3%Pt/C(PMQ: Lot # 30936, Active material: 46% The present invention does not limit itself to the use of the catalyst mentioned here, Many other similar catalyst such platinum on carbon, platinum on charcoal, platinum oxide, and such other noble metal catalyst can be used for the purpose of this invention. This will also include different parameters such as quantity of the catalyst for the reaction and forms like sulfided, non sulfided, sulfited and other methods of passivation used, Similarly various amounts of platinum on carbon ,and particle size, dispersion, and other properties of catalyst are also included in the scope of the present invention. Similarly with respect to the reaction conditions used in the present invention different range of temperature from 30 °C to 150 °C, and pressure from 2 kgs to 60 kgs , catalyst percentage on nitro compound used from 0.05% to 5%, are included in the scope of the present invention. EXAMPLE 4 The details and results of preparation of nitroether are presented below Procedure for the preparation of nitroether [5-chloro-2-(2,4-dichlorophenoxy)nitrobenzene]: To molten DCP (2,4,dichlorophenol) in a reactor, KOH flakes are added in lots taking care that the temperature does not increase above 110°C. First lot of water is then added and the resulting solution is maintained at 110°C for 30min. DCNB (2,5 dichloronitrobenzene) is then added in single installment and the reaction mass temperature is increased to 150°C, during which, water is distilled out. The reaction is continued for a period of 3-4 hours, during which, the DCNB content in the reaction mass reaches below 0.1%. After the reaction is complete, the reaction mass is cooled to 130°C and second lot of water is added which is followed by 10% NaOH solution and the third lot of water. The heterogeneous mass thus obtained is then cooled to room temperature and filtered to separate nitroether from aqueous salt solution. The solid is then washed with water till the washings are free from sodium, potassium or chloride ions. Sr No Chemical Name Mol Wt Moles Quantity Kg Wt% 1 2,4-dichlorophenol 163 0.21 35 17.08 2 Potassium hydroxide 56 0.25 13.93 6.80 3 Water (I lot) 18 0.095 1.715 0.837 4 2,5-dichloronitrobenzene 192 0.21 41.09 20.05 5 Water (11 lot) 18 1.59 28.56 13.94 6 10% NaOH solution - - 27.5 13.41 7 Water (III lot) 18 3.17 57.10 27.87 The yield of nitroether thus obtained is 95% based on the DCNB charged and the purity is 98-99.5%.

Full Text

FORM 2
THE PATENTS ACT 1970
(39 of 1970)
&
The Patent Rules, 2003
Provisional Specification
(See section 10 and rule 13)

A process for preparation of 5-chloro-2-(2,4-dichlorophenoxy)aniline

Dorf Ketal Chemicals (I) Pvt. Ltd
Dorf Ketal Tower, D'monte Street, Orlem, Malad (W), Mumbai, 400064 Maharashtra
State, India
An Indian company registered under the Companies Act, 1956
The following specification describes the invention:

A process for preparation of 5-chloro-2-(2,4-dichlorophenoxy)aniline
Field of invention
The Invention relates to a process for the preparation of halogenated aromatic primary amines such as triclosan amine which is 5-chloro-2-(2,4-dichlorophenoxy)aniline, by catalytic hydrogenation of the corresponding halogenated aromatic nitro compounds in the presence of noble metal catalyst such platinum supported on carbon
Discussion of prior art
It is known that halogenated aromatic primary amines are obtained by catalytic hydrogenation of their corresponding halogenated aromatic nitro compounds. The hydrogenation additionally leads to dehalogenation thus to giving mixtures of dehalogenated and halogenated aromatic primary amines which are difficult to separate.
The inventor of the present invention has performed several laboratory experiments to verify the conventional method used in reduction nitroether to form corresponding amine. The experimental details and results of one such experiment are presented in example 1 given below:
EXAMPLE 1
Preparation of Triclosan amine

The details given in Table 1, Table 2, and the procedural steps given below explain the method used for preparing Triclosan amine.

Batch no: RM/IV/81
TABLE 1

Chemical name 5-chloro-2-(2,4-dichlorophenoxy)nitrobenzene 5-chloro-2-(2,4-dichlorophenoxy)aniline
(Nitro ether) Purity = 99.36% (Amine)
Mol wt 318.5 288.5
TABLE 2

Chemical name Weight (grams)
5-chloro-2-(2,4-dichlorophenoxy)nitrobenzene 131.3 g (solid content 80%)
Iron powder 112.5 g (five lots of 22.5 g each)
Acetic acid 6.1 g
Water 125 g
5-chloro-2-(2,4-dichlorophenoxy)aniline(product) 79.2 g
Procedure:
Following steps were used in the experiment:
(1) 131.3 gms of nitroether and 125 gms of water are taken in 4 necked round bottom flask equipped with stirrer, condenser, thermometer, and inlet for nitrogen gas.
(2) To the above add first lot of iron powder and acetic acid in that order, as mentioned in table 2.
(3) Heat the reaction mixture to 90 °C.
(4) Add remaining lots of iron powder at interval of 30 minutes each. Frothing is observed during addition of iron powder.

(5) . Maintain temperature at 90 C to 95 C and monitor the reaction (till
absence of Nitro ether) by TLC/GC. ( Thin layer chromatography and gas
chromatography)
(6) Upon completion of reaction, add Toluene (150 g).
(7) Reflux reaction mixture for 1 hour.
(8) Cool to 55 to 60°C.
(9) Filter reaction mass.
(10) Wash Iron powder in the filter paper with hot additional Toluene (150 g).

(11) Collect reaction mixture and washings of Iron powder.
(12) Separate aqueous layer from toluene layer.
(13) Toluene layer is washed with water (125 g).
(14) Remove toluene by distillation. The purity of this amine is 99.39%
(15) The above prepared amine that is 5-chloro-2-(2,4-dichlorophenoxy)aniline is used to make final product that is triclosan. (Instead of toluene, other solvents like chloroethylene also can be used.)
Mole ratio = 5-chloro-2-(2, 4-dichlorophenoxy) nitrobenzene: Iron =1: 6.1 GC Purity = 99.39% (purity of amine) Yield=83.4% (yield of amine)
The disadvantage of the above process are:
1 The iron powder has to be used in almost in the 1: 1 weight ratio of the amine. This lowers the output.
2 The recovered iron is not suitable for the next reaction and hence cannot be recycled. Hence disposal of this iron powder contaminated with the amine poses an environmental problem.
3 Amine is retained in the iron powder even after washings, hence there are losses.

Hence there is a perceived necessity of finding alternative method to make 5-chloro-2-(2,4-dichlorophenoxy)aniline to overcome the above mentioned disadvantages and which will be economical and environmental friendly.
Description of Invention
Accordingly the steps used in the present invention are described below with reference to most preferred embodiment the invention.
General procedure of the invention for the hydrogenation of nitroetherto Amine:
1. Nitroether, that is, 5-chloro-2-(2,4-dichlorophenoxy)nitrobenzene, methanol
and the catalyst are charged to the autoclave which is then closed.
2. The autoclave is flushed with nitrogen three times to displace air followed by
hydrogen three times.
3. The autoclave is then pressurized with hydrogen.
4. Agitation and heating is then started.
5. The reaction mass is maintained at the desired temperatures throughout the reaction by providing cooling if required.
6. After the reaction is complete, that is, there is no hydrogen uptake, the reaction mass is cooled.
7. The autoclave is vented and flushed with nitrogen three times.
8. The reaction mass is then filtered to separate the catalyst. The separated catalyst can be reused for subsequent reactions.
9. Methanol is distilled out along with water formed during the reaction.

10. Traces of water in the amine thus obtained are removed under reduced pressure at 120°C. The final amine is anlaysed by gas chromatography for purity.
11. The above prepared amine that is 5-chloro-2-(2,4-dichlorophenoxy)aniline is used to make final product that is triclosan
The above mentioned procedural steps are used in conducting laboratory experiments, the details and results of which are given in example 2

EXAMPLE 2
The details of the ingredients used in the experiments and the results achieved therefrom are given below in Table 3
TABLE 3

Ingredients Expt No 1 Expt No2 Exptno3
Nitrocompound,5-chloro-2-(2,4dichlorophenoxy)nitrobenzene lOOgms lOOgms lOOgms
Methanol lOOgms lOOgms lOOgms
Catalyst
Raney Nickel 5.0gms 5.0gms
Pt/c 1.44gms
Temperature 40 to 60 degc 105 degc 40-60 degc
Pressure 25kgs lOkgs 25kgs
Reaction Time 3.5hrs lOhrs 2.15 hrs
GC analysis In% In% In%
Product 5-chloro-2-(2,4-dichlorophenoxy)aniline 92.4475 93.3114 99.3514
Dehalogenated Produer 7.3783 5.1654 0.5750
Details of the catalysts used for the hydrogenation in these experiments are given below:
Raney Ni:
Monarch Catalysts Pvt. Ltd.,
KALCAT-8030
Lot # 092
3%Pt/C(PMQ:
Lot # 30936, Active material: 46%

The present invention does not limit itself to the use of the catalyst mentioned here, Many other similar catalyst such platinum on carbon, platinum on charcoal, platinum oxide, and such other noble metal catalyst can be used for the purpose of this invention. This will also include different parameters such as quantity of the catalyst for the reaction and forms like sulfided, non sulfided, sulfited and other methods of passivation used, Similarly various amounts of platinum on carbon ,and particle size, dispersion, and other properties of catalyst are also included in the scope of the present invention.
Similarly with respect to the reaction conditions used in the present invention different range of temperature from 30 °C to 150 °C, and pressure from 2 kgs to 60 kgs , catalyst percentage on nitro compound used from 0.05% to 5%, are included in the scope of the present invention.
EXAMPLE 4
The details and results of preparation of nitroether are presented below
Procedure for the preparation of nitroether [5-chloro-2-(2,4-dichlorophenoxy)nitrobenzene]:
To molten DCP (2,4,dichlorophenol) in a reactor, KOH flakes are added in lots taking care that the temperature does not increase above 110°C. First lot of water is then added and the resulting solution is maintained at 110°C for 30min. DCNB (2,5 dichloronitrobenzene) is then added in single installment and the reaction mass temperature is increased to 150°C, during which, water is distilled out. The reaction is continued for a period of 3-4 hours, during which, the DCNB content in the reaction mass reaches below 0.1%. After the reaction is complete, the reaction mass is cooled to 130°C and second lot of water is added which is followed by 10% NaOH solution and the third lot of water. The heterogeneous

mass thus obtained is then cooled to room temperature and filtered to separate nitroether from aqueous salt solution. The solid is then washed with water till the washings are free from sodium, potassium or chloride ions.

Sr No Chemical Name Mol Wt Moles Quantity Kg Wt%
1 2,4-dichlorophenol 163 0.21 35 17.08
2 Potassium hydroxide 56 0.25 13.93 6.80
3 Water (I lot) 18 0.095 1.715 0.837
4 2,5-dichloronitrobenzene 192 0.21 41.09 20.05
5 Water (11 lot) 18 1.59 28.56 13.94
6 10% NaOH solution - - 27.5 13.41
7 Water (III lot) 18 3.17 57.10 27.87
The yield of nitroether thus obtained is 95% based on the DCNB charged and the
purity is 98-99.5%.

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Patent Number

253022

Indian Patent Application Number

2029/MUM/2007

PG Journal Number

25/2012

Publication Date

22-Jun-2012

Grant Date

15-Jun-2012

Date of Filing

12-Oct-2007

Name of Patentee

DORF KETAL CHEMICALS (I) PVT. LTD

Applicant Address

DORF KETAL TOWER, D'MONTE STREET, ORLEM, MALAD (W) MUMBAI

Inventors:

#	Inventor's Name	Inventor's Address
1	SUBRAMANIYAM MAHESH	DORF KETAL TOWER, D'MONTE STREET, ORLEM, MALAD (W) MUMBAI 400064

PCT International Classification Number

C07C211/52

PCT International Application Number

N/A

PCT International Filing date

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1			NA