Title of Invention	"AN IMPROVED PROCESS FOR DENITROCHLORINATION OF CHLOROFLUORO-NITROBENZENES TO 2,4-DICHLOROFLUOROBENZENE".
Abstract	An improved process for denitrochlorination of chlorofluoronitrobenzenes to 2,4-dichlorofluorobenzenes by reacting chlorofluoronitrobenzenes with chlorine into bubble column reactor, distilling at a temperature in the range of 150-240°C, at a flow rate of chlorine in the range of 40-120cc/min, at a flow rate of chlorofluoronitrobenzenes in the range of 5-45 g/h, for a period in the range of 150-400 seconds, optionally adding a quarternary ammonium salt washing the condensate obtained by water and alkali till the pH of the condensate is neutralized, drying the organic layer to obtain the desired pure 2,4-dichlorofluorobenzenes.

Title of Invention

"AN IMPROVED PROCESS FOR DENITROCHLORINATION OF CHLOROFLUORO-NITROBENZENES TO 2,4-DICHLOROFLUOROBENZENE".

Abstract

An improved process for denitrochlorination of chlorofluoronitrobenzenes to 2,4-dichlorofluorobenzenes by reacting chlorofluoronitrobenzenes with chlorine into bubble column reactor, distilling at a temperature in the range of 150-240°C, at a flow rate of chlorine in the range of 40-120cc/min, at a flow rate of chlorofluoronitrobenzenes in the range of 5-45 g/h, for a period in the range of 150-400 seconds, optionally adding a quarternary ammonium salt washing the condensate obtained by water and alkali till the pH of the condensate is neutralized, drying the organic layer to obtain the desired pure 2,4-dichlorofluorobenzenes.

Full Text	The present invention relates to an improved process for denitrochlorination of chlorofluoronitrobenzenes to 2,4-dichlorofluorobenzene. 2,4-Dichlorofluorobenzene (2,4-DCFB) is an important organic intermediate for the synthesis of quinolone class of antibacterial compounds. Different methods of preparation of 2,4-dichlorofluorobenzene are known in the art. Pallash (Acta Chim. Acad. Sci. Hung 10:227-232, 1956) have reported by diazotisation of 2,4-dichloroaniline and introduced the fluorine using Balz - Schiemann reaction. Also 3-chloro -4- aniline was transformed into 2,4-dichlorofluorobenzene using sandmeyer reaction for introducing chlorine function. The cost of the raw materials used in the above two processes was high and diazotisation methods are difficult for operation on commercial scale. Subsequently a new method involving denitrochlorination of a suitably substituted fluorine containing nitrobenzene was applied. Thus 2,4-dinitrofluorobenzene (zhur obshche Khim. 31: 1222-1226, JP. 01226836,1989) used for denitrochlorination at higher temperature to give 2,4-dichlorofluorobenzene. This method was unsafe because of handling dinitrocompound industrially at higher temperature. Ohashi (JP 0126538, 1989), Kumai (JP. 0259529, 1990) and seimi chemicals limited (SH 0-64, 26538,1989) used 2—fluoro-5-chloronitrobenzene to give 2,4-dichlorofluorobenzene in a batch process. Chinese Patent CN. 10709004 A (1993) claims a process starting from o-dichlorobenzene involving three steps of nitration , halogen exchange reaction and denitrochlorination. This process is further improved by using a less expensive mixture of o- and p- dichlorobenzenes as starting materials. The yield in the denitrochlorination reaction is around 60%. Japanese Patent HEI-2-59529 (1990) discloses the denitrochlorination of 3-chloro-4-fluoronitrobenzene using nitryle chloride (NOjCI) in a nickel tube at 400°C gives 2,4-dichlorofluorobenzene. For a commercial process, high temperatures are not desirable. The earlier methods have not referred to the formation of highly hazardous poly halogenated benzenes under the conditions employed. Thus all methods cited above have got disadvantages over the developed process which involves reactive distillation. The present invention describes an improved process for the preparation of 2,4-dichlorofluorobenzene from an isomeric mixture of chlorofluoronitrobenzenes. The main objective of the present invention is to provide an improved process for denitrochlorination of an isomeric mixture of chlorofluoronitrobenzenes to 2,4-dichlorofluorobenzene. The other objective of the present invention is to provide a novel and continuous process involving reactive distillation which is viable for commercialization. Yet another objective is to suppress the nuclear chlorination leading to the formation of polyhalogenated benzenes. Accordingly, the present invention provides an improved process for denitrochlorination of chlorofluoronitrobenzenes to 2,4-dichlorofluorobenzenes which comprises reacting chlorofluoronitrobenzenes with chlorine into bubble column reactor, distilling at a temperature in the range of 150-240°C, at a flow rate of chlorine in the range of 40-120cc/min, at a flow rate of chlorofluoronitrobenzenes in the range of 5-45 g/h, for a period in the range of 150-400 seconds, optionally adding a quaternary ammonium salt washing the condensate obtained by water and alkali till the pH of the condensate is neutralized, drying the organic layer to obtain the desired pure 2,4- dichlorofluorobenzenes. In an embodiment of the present invention the chlorofluoronitrobenzenes used is a isomeric mixture of 3-chloro-4-fluoronitrobenzene and 2-fluoro-5-chloronitrobenzene In yet another embodiment the process used is continuous by cofeeding chlorofluoronitrobenzenes and chlorine. In yet another embodiment the reaction temperature is preferably in the range of 165 -225°C In yet another embodiment the flow rate of chlorine used is preferably in the range of 50 -l00cc/min In yet another embodiment the flow rate of CFNBs used is preferably in the range 20-30g/h. In yet another embodiment the contact time of chlorine to chlorofluoronitrobenzenes used is preferably in the range of 250-300 sec. In still another embodiment the quarternary ammonium salt used is trimethylaminehydrochloride. The present invention relates to an improved process for denitrochlorination of chlorofluoronitrobenzenes to 2,4-dichlorofluorobenzene. A stream of chlorine and isomeric mixture of chlorofluoronitrobenzenes are cofed in to a packed glass tubular bubble reactor via a preheater at pre determined rates .The reactor column is also filled with isomeric mixture of chlorofluoronitrobenzenes. The reaction temperatures are maintained in the range 140-240° C and preferably in the range 160-220° C and more preferably in the range 170-210° C. The passage of chlorine through reactor is in the range 40-120 cc/min and more preferably between 60-100 cc/min. During the course of the reaction the vapor crude dichlorofluorobenzene and nitrylchloride along with unreacted chlorine from the reactor are passed through a water-cooled condenser. Dichlorofluorobenzene and partly nitrylchloride are collected in a receiver. The unreacted chlorine and uncondensed vent gases are scrubbed with 15-25% aqueous sodium hydroxide. The reaction is a continuous process, which is more desirable on a commercial scale. The usage of catalytic amount of quaternary ammonium salts like trimethyl ammonium chloride etc., in the reaction may increase the yield of desired product. The reactive distillation technique is always favorable in minimizing the side products formation. The down stream process includes isolation and purification of the 2,4-dichlorofiuorobenzene in the conventional manner. The present invention is described with reference to the following examples, which are explained by way of illustration and should not therefore be construed to limit the scope of the invention. Example-1: 1" Dia glass tubular bubble reactor of 60 cm length packed with glass beads (6x4) is charged with isomeric mixture of chlorofluoronitrobenzenes approximately to half of its height. The column is heated with block furnaces and the skin temperature is monitored and maintained at about 200° C using PID controllers. The chlorine is fed from the bottom of the reactor via a preheater when the liquid temperature inside the reactor attains 140° C or more. Once the liquid temperature reached 175° C or more the product start distilling and the chlorofluoronitrobenzenes are also fed into the reactor at 16 g/h. to maintain the liquid level in the reactor for 24 h. The temperature of the vapor at the column exit is continuously monitored by a thermocouple kept in a thermowell. The condensate obtained is washed successively with water,alkali and water till washings are neutral to pH.The organic layer is dried over anhydrous sodium sulfate and distilled under reduced pressure ,collect the pure 2,4-dichlorofluorobenzene 258g (98%) at 50-60° at 70 mm/Hg, yield 70%.During the reaction the condensed vapors are scrubbed in alkali. Example-2: The denitrochlorination reaction of chlorofluoronitrobenzene is carried out the exactly the same way as that in example -1, except that the trimethylaminehydrochloride (1g) is charged in the reactor and the feed of chlorofluoronitrobenzene is also increased to 25 g/h. The result showed the formation of 2,4-dichlorofluorobenzene is 445 g (98%) and yield is 77%. Advantages: The main advantage of this improved process is a continuous process of denitrochlorination of chlorofluoronitrobenzenes by cofeeding chlorine and chlorofluoronitrobenzenes into tubular bubble column reactor and isolating the product by reactive distillation. Other advantages of the process are the feed of chlorine made as the limiting factor, which minimizes the waste disposal problem. Another advantage of the process is that the formation of the poly-halogenated products is minimum. We claim: 1. An improved process for denitrochlorination of chlorofluoronitrobenzenes to 2,4-dichlorofluorobenzenes which comprises reacting chlorofluoronitrobenzenes with chlorine into bubble column reactor, distilling at a temperature in the range of 150-240°C, at a flow rate of chlorine in the range of 40-120cc/min, at a flow rate of chlorofluoronitrobenzenes in the range of 5-45 g/h, for a period in the range of 150-400 seconds, optionally adding a quarternary ammonium salt washing the condensate obtained by water and alkali till the pH of the condensate is neutralized, drying the organic layer to obtain the desired pure 2,4- dichlorofluorobenzenes. 2. An improved process as claimed in claim 1 wherein the chlorofluoronitrobenzenes used is a isomeric mixture of 3-chloro-4- fluoronitrobenzene and 2-fluoro-5-chloronitrobenzene. 3. An improved process as claimed in claims 1-2 wherein the reaction temperature is preferably in the range of 165-225°C. 4. An improved process as claimed in claims 1-3 wherein the flow rate of chlorine used is preferably in the range of 50-100 cc/min. 5. An improved process as claimed in claims 1-4 wherein the flow rate of chlorofluoronitrobenzene used is preferably in the range of 20-30g/h. 6. An improved process as claimed in claims 1-5 wherein the contact time of chlorine to chlorofluoronitrobenzenes used is preferably in the range of 250-300 sec. 7. An improved process as claimed in claims 1-6 wherein the quarternary ammonium salt used is trimethylaminehydrochloride. 8. An improved process for denitrochlorination of chlorofluoronitrobenzenes to 2,4-dichlorofluorobenzenes substantially as herein described with reference to the examples.

Full Text

The present invention relates to an improved process for denitrochlorination of chlorofluoronitrobenzenes to 2,4-dichlorofluorobenzene.
2,4-Dichlorofluorobenzene (2,4-DCFB) is an important organic intermediate for
the synthesis of quinolone class of antibacterial compounds. Different methods of
preparation of 2,4-dichlorofluorobenzene are known in the art. Pallash (Acta Chim. Acad.
Sci. Hung 10:227-232, 1956) have reported by diazotisation of 2,4-dichloroaniline and introduced the fluorine using Balz - Schiemann reaction. Also 3-chloro -4- aniline was transformed into 2,4-dichlorofluorobenzene using sandmeyer reaction for introducing chlorine function. The cost of the raw materials used in the above two processes was high and diazotisation methods are difficult for operation on commercial scale. Subsequently a new method involving denitrochlorination of a suitably substituted fluorine containing nitrobenzene was applied. Thus 2,4-dinitrofluorobenzene (zhur obshche Khim. 31: 1222-1226, JP. 01226836,1989) used for denitrochlorination at higher temperature to give 2,4-dichlorofluorobenzene. This method was unsafe because of handling dinitrocompound industrially at higher temperature. Ohashi (JP 0126538, 1989), Kumai (JP. 0259529, 1990) and seimi chemicals limited (SH 0-64, 26538,1989) used 2—fluoro-5-chloronitrobenzene to give 2,4-dichlorofluorobenzene in a batch process. Chinese Patent CN. 10709004 A (1993) claims a process starting from o-dichlorobenzene involving three steps of nitration , halogen exchange reaction and denitrochlorination. This process is further improved by using a less expensive mixture of o- and p- dichlorobenzenes as starting materials. The yield in the denitrochlorination reaction is around 60%. Japanese
Patent HEI-2-59529 (1990) discloses the denitrochlorination of 3-chloro-4-fluoronitrobenzene using nitryle chloride (NOjCI) in a nickel tube at 400°C gives 2,4-dichlorofluorobenzene. For a commercial process, high temperatures are not desirable. The earlier methods have not referred to the formation of highly hazardous poly halogenated benzenes under the conditions employed. Thus all methods cited above have got disadvantages over the developed process which involves reactive distillation.
The present invention describes an improved process for the preparation of 2,4-dichlorofluorobenzene from an isomeric mixture of chlorofluoronitrobenzenes. The main objective of the present invention is to provide an improved process for denitrochlorination of an isomeric mixture of chlorofluoronitrobenzenes to 2,4-dichlorofluorobenzene. The other objective of the present invention is to provide a novel and continuous process involving reactive distillation which is viable for commercialization. Yet another objective is to suppress the nuclear chlorination leading to the formation of polyhalogenated benzenes.
Accordingly, the present invention provides an improved process for denitrochlorination of chlorofluoronitrobenzenes to 2,4-dichlorofluorobenzenes which comprises reacting chlorofluoronitrobenzenes with chlorine into bubble column reactor, distilling at a temperature in the range of 150-240°C, at a flow rate of chlorine in the range of 40-120cc/min, at a flow rate of chlorofluoronitrobenzenes in the range of 5-45 g/h, for a period in the range of 150-400 seconds, optionally adding a quaternary ammonium salt washing the condensate obtained by water and alkali till the pH of the condensate is neutralized, drying the organic layer to obtain the desired pure 2,4- dichlorofluorobenzenes.
In an embodiment of the present invention the chlorofluoronitrobenzenes used is a isomeric mixture of 3-chloro-4-fluoronitrobenzene and 2-fluoro-5-chloronitrobenzene
In yet another embodiment the process used is continuous by cofeeding chlorofluoronitrobenzenes and chlorine.
In yet another embodiment the reaction temperature is preferably in the range of 165 -225°C
In yet another embodiment the flow rate of chlorine used is preferably in the range of 50 -l00cc/min
In yet another embodiment the flow rate of CFNBs used is preferably in the range 20-30g/h.
In yet another embodiment the contact time of chlorine to chlorofluoronitrobenzenes used is preferably in the range of 250-300 sec.
In still another embodiment the quarternary ammonium salt used is trimethylaminehydrochloride.
The present invention relates to an improved process for denitrochlorination of chlorofluoronitrobenzenes to 2,4-dichlorofluorobenzene. A stream of chlorine and isomeric mixture of chlorofluoronitrobenzenes are cofed in to a packed glass tubular bubble reactor via a preheater at pre determined rates .The reactor column is also filled with isomeric mixture of chlorofluoronitrobenzenes. The reaction temperatures are maintained in the range 140-240° C and preferably in the range 160-220° C and more preferably in the range 170-210° C. The passage of chlorine through reactor is in the range 40-120 cc/min and more preferably between 60-100 cc/min. During the course of the reaction the vapor crude dichlorofluorobenzene and nitrylchloride along with unreacted chlorine from the reactor are passed through a water-cooled condenser. Dichlorofluorobenzene and partly nitrylchloride are collected in a receiver. The unreacted
chlorine and uncondensed vent gases are scrubbed with 15-25% aqueous sodium hydroxide. The reaction is a continuous process, which is more desirable on a commercial scale. The usage of catalytic amount of quaternary ammonium salts like trimethyl ammonium chloride etc., in the reaction may increase the yield of desired product. The reactive distillation technique is always favorable in minimizing the side products formation. The down stream process includes isolation and purification of the 2,4-dichlorofiuorobenzene in the conventional manner.
The present invention is described with reference to the following examples, which are explained by way of illustration and should not therefore be construed to limit the scope of the invention.
Example-1:
1" Dia glass tubular bubble reactor of 60 cm length packed with glass beads (6x4) is charged with isomeric mixture of chlorofluoronitrobenzenes approximately to half of its height. The column is heated with block furnaces and the skin temperature is monitored and maintained at about 200° C using PID controllers. The chlorine is fed from the bottom of the reactor via a preheater when the liquid temperature inside the reactor attains 140° C or more. Once the liquid temperature reached 175° C or more the product start distilling and the chlorofluoronitrobenzenes are also fed into the reactor at 16 g/h. to maintain the liquid level in the reactor for 24 h. The temperature of the vapor at the column exit is continuously monitored by a thermocouple kept in a thermowell. The condensate obtained is washed successively with water,alkali and water till washings are neutral to pH.The organic layer is dried over anhydrous sodium sulfate and distilled under reduced pressure ,collect the pure 2,4-dichlorofluorobenzene 258g (98%) at 50-60° at 70 mm/Hg, yield 70%.During the reaction the condensed vapors are scrubbed in alkali.
Example-2:
The denitrochlorination reaction of chlorofluoronitrobenzene is carried out the exactly the same way as that in example -1, except that the trimethylaminehydrochloride (1g) is charged in the reactor and the feed of chlorofluoronitrobenzene is also increased to 25 g/h. The result showed the formation of 2,4-dichlorofluorobenzene is 445 g (98%) and yield is 77%.
Advantages:
The main advantage of this improved process is a continuous process of denitrochlorination of chlorofluoronitrobenzenes by cofeeding chlorine and chlorofluoronitrobenzenes into tubular bubble column reactor and isolating the product by reactive distillation. Other advantages of the process are the feed of chlorine made as the limiting factor, which minimizes the waste disposal problem. Another advantage of the process is that the formation of the poly-halogenated products is minimum.

We claim:
1. An improved process for denitrochlorination of chlorofluoronitrobenzenes
to 2,4-dichlorofluorobenzenes which comprises reacting chlorofluoronitrobenzenes with chlorine into bubble column reactor, distilling at a temperature in the range of 150-240°C, at a flow rate of chlorine in the range of 40-120cc/min, at a flow rate of chlorofluoronitrobenzenes in the range of 5-45 g/h, for a period in the range of 150-400 seconds, optionally adding a quarternary ammonium salt washing the condensate obtained by water and alkali till the pH of the condensate is neutralized, drying the organic layer to obtain the desired pure 2,4- dichlorofluorobenzenes.
2. An improved process as claimed in claim 1 wherein the chlorofluoronitrobenzenes used is a isomeric mixture of 3-chloro-4- fluoronitrobenzene and 2-fluoro-5-chloronitrobenzene.
3. An improved process as claimed in claims 1-2 wherein the reaction temperature is preferably in the range of 165-225°C.
4. An improved process as claimed in claims 1-3 wherein the flow rate of chlorine used is preferably in the range of 50-100 cc/min.
5. An improved process as claimed in claims 1-4 wherein the flow rate of chlorofluoronitrobenzene used is preferably in the range of 20-30g/h.
6. An improved process as claimed in claims 1-5 wherein the contact time of
chlorine to chlorofluoronitrobenzenes used is preferably in the range of
250-300 sec.
7. An improved process as claimed in claims 1-6 wherein the quarternary
ammonium salt used is trimethylaminehydrochloride.
8. An improved process for denitrochlorination of chlorofluoronitrobenzenes
to 2,4-dichlorofluorobenzenes substantially as herein described with
reference to the examples.

Documents:

103-del-2001-abstract.pdf

103-del-2001-claims.pdf

103-del-2001-correspondence-others.pdf

103-del-2001-correspondence-po.pdf

103-del-2001-description (complete).pdf

103-del-2001-form-1.pdf

103-del-2001-form-19.pdf

103-del-2001-form-2.pdf

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Patent Number

209453

Indian Patent Application Number

103/DEL/2001

PG Journal Number

38/2007

Publication Date

21-Sep-2007

Grant Date

30-Aug-2007

Date of Filing

31-Jan-2001

Name of Patentee

COUNCIL OF SCIENTIFIC AND INDUSTRIAL RESEARCH

Applicant Address

RAFI MARG, NEW DELHI - 110 001, INDIA.

Inventors:

#	Inventor's Name	Inventor's Address
1	PAMULAPARTHY SHANTHAN RAO	INSTITUTE OF CHEMICAL TECHNOLOGY, HYDERABAD - 500 007, ANDHRA PRADESH, INDIA.
2	JAMPANI MADHUSUDANA RAO	INSTITUTE OF CHEMICAL TECHNOLOGY, HYDERABAD - 500 007, ANDHRA PRADESH, INDIA.
3	BANDA NARSAIAH	INSTITUTE OF CHEMICAL TECHNOLOGY, HYDERABAD - 500 007, ANDHRA PRADESH, INDIA.
4	YADLA RAMBABU	INSTITUTE OF CHEMICAL TECHNOLOGY, HYDERABAD - 500 007, ANDHRA PRADESH, INDIA.
5	SRIPATHI NARAYAN REDDY	INSTITUTE OF CHEMICAL TECHNOLOGY, HYDERABAD - 500 007, ANDHRA PRADESH, INDIA.
6	MADABHUSHI SRIDHAR	INSTITUTE OF CHEMICAL TECHNOLOGY, HYDERABAD - 500 007, ANDHRA PRADESH, INDIA.
7	MALVAY ESHWAR RAO	INSTITUTE OF CHEMICAL TECHNOLOGY, HYDERABAD - 500 007, ANDHRA PRADESH, INDIA.

PCT International Classification Number

C07C 17/22

PCT International Application Number

N/A

PCT International Filing date

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1			NA