Description:FORM 2
THE PATENT ACT 1970
(39 of 1970)
&
THE PATENT RULES, 2003
COMPLETE SPECIFICATION
(See section 10 and rule 13)

“PROCESS FOR PREPARATION OF DICHLOROPYRIDINE”
This patent application is an alternative process to the one filed in IN202111043062 filed on 23 September 2021 by the same applicant

SRF LIMITED, AN INDIAN COMPANY,
SECTOR 45, BLOCK-C, UNICREST BUILDING,
GURGAON – 122003,
HARYANA (INDIA)

The following specification particularly describes the invention and the manner in which it is to be performed.

FIELD OF THE INVENTION
The present invention provides a process for preparation of dichloropyridine, which is useful as an intermediate for pharmaceutical and agrochemical industries.

BACKGROUND OF THE INVENTION
2,3-Dihalopyridine compounds, especially 2,3-dichloropyridine are important intermediates for fine chemical industry. The 2,3-dichloropyridine is an important raw material for the preparation of agrochemicals, pharmaceutical and other fine chemicals.
U.S. Pat. No. 4,515,953 discloses the liquid phase chlorination of pyridine or pyridine hydrochloride. The products obtained by this process include 2,3-dichloropyridine along with other polychlorinated pyridine mixture. Several purification steps are required to extract 2,3-dichloropyridine.
J. Org. Chem., 1962, 27, 3965-8 discloses a process for the preparation of 2,3-difluoropyridine from 3-amino-2-fluoropyridine by diazotization of 3-amino-2-fluoropyridine with ethyl nitrite in fluoroboric acid. 3-amino-2-fluoropyridine in turn is prepared from 2-fluoropyridine-3-carboxamide by the Hofmann reaction. The yield of 2,3-difluoropyridine prepared by this process is very low (20%).
U.S. Pat. No. 6,224,2631 discloses a process for preparation of 2,3-dichloropyridine by halogenation of 2-chloro-3-nitropyridine with phenylphosphorous tetrachloride and benzene phosphorus dichloride.
PCT application No. 2005070888 discloses a four-step process for preparing 2,3-dichloropyridine in which 3-amino-2-chloropyridine is contacted with an alkali metal nitrite in the presence of aqueous hydrochloric acid to form a diazonium salt; subsequently the diazonium salt is decomposed in the presence of copper catalyst wherein at least about 50% of the copper is in the copper (II) to form 2,3-dichloropyridine.
PCT application No. 2009114589 discloses a process for preparing 2,3-dichloropyridine involving a reaction of 3-amino-2-chloropyridine with a nitrite salt in the presence of aqueous hydrochloric acid to form a diazonium salt; and the diazonium salt is subsequently decomposed in the presence of sulfamic acid and a copper catalyst wherein at least about 50% of the copper is the copper (II) oxidation state.
Indian Patent Application 202111043062 filed by the same applicant discloses a process for preparation of dichloropyridine by de-halogenating trichloropyridine.
The dichloropyridine produced by the processes disclosed in the literature is impure and requires several steps for extraction and isolation. In addition, the processes involve consumption of solvents in huge quantities, thereby making them costly and non-viable for industrial production.
The present invention provides a highly selective and industrially viable process for the preparation of dichloropyridine with high purity and yield.

OBJECT OF THE INVENTION
The main object of the present invention is to provide a simple, cost effective and an environment friendly process for the preparation of dichloropyridine.

SUMMARY OF THE INVENTION
The present invention provides a process for preparation of dichloropyridine, comprising a step of diazotization and a continuous stirred reactor.

DETAILED DESCRIPTION OF THE INVENTION
The present invention provides a process for preparation of dichloropyridine, comprising the steps of:
a) contacting a solution of 2-aminochloropyridine in hydrochloric acid with a diazotizing agent in a continuous stirred reactor 1;
b) quenching the diazotized mass of step a) with copper (I) salt in presence of a nitrous acid scavenger in another continuous stirred reactor 2;
c) isolating dichloropyridine.
In an embodiment of the present invention, the dichloropyridine is selected from a group consisting of 2,3-dichloropyridine; 2,4-dichloropyridine, 2,5-dichloropyridine and 2,6-dichloropyridine.
In another embodiment of the present invention, 2-aminochloropyridine is selected from a group consisting of 2-amino-3-chloropyridine; 2-amino-4-chloropyridine, 2-amino-5-chloropyridine and 2-amino-6-chloropyridine.
In another embodiment of the present invention, a solution of 2-aminochloropyridine in hydrochloric acid is added to a continuous stirred reactor at a flow rate of 4.0 to 5.0g per minute.
In another embodiment of the present invention, the aqueous solution of diazotizing agent is added to a continuous stirred reactor at a flow rate of 0.9g per minute to 1.5g per minute.
In another embodiment of the present invention, the residence time of each reactor is about 20 minutes to 5 hours.
In another embodiment of the present invention, the temperature of the continuous stirred reactor 1 is in the range -5 to 10°C.
In another embodiment of the present invention, the temperature of continuous reactor 2 is in the range of 40 to 80°C.
In another embodiment of the present invention, the step a) and step b) are carried out in absence of any organic solvent. The absence of an organic solvent in these steps reduces the chance of formation of impurities.
In another embodiment of the present invention, the diazotization agent is selected from a group consisting of sodium nitrite, potassium nitrite, t-butyl nitrite, and nitrosyl sulfuric acid or the like.
In another embodiment of the present invention the step of quenching is carried out using copper (I) chloride in presence of sulfamic acid, wherein copper (I) chloride is present at least 50-90%.
In another embodiment of the present invention, the dichloropyridine is isolated using an organic solvent 1 and an organic solvent 2 selected from group consisting of chloroform, dichloromethane, carbon tetrachloride, hexane, and toluene or the mixture thereof.
In another embodiment of the present invention, the nitrous acid scavenger is selected from a group consisting of sulfamic acid, urea, and p-nitroaniline or the like.
In another embodiment of the present invention, the step of isolation removes multi-chlorinated impurities selected from a group consisting of 2,3,4-trichloropyridine; 2,3,6-trichloropyridine, 2,3,5-trichloropyridine, and 2,4,6-trichloropyridine or the like.
In another embodiment of the present invention, the step of quenching is carried out at a temperature of 40°C to 80°C. The low temperature range prevents the degradation of product and improves yield significantly.
The absence of an organic solvent in the step of diazotization and quenching and the use of continuous stirred reactor provides following advantages over the known methods:
1. The present invention reduces the number of operations at the industrial scale thereby making it cost effective.
2. The present invention reduces the formation of impurities in the final dichloropyridine.
3. The process of present invention provides efficient recycling and recovery of extracting solvents.
4. The process of present invention is scalable and economically viable because it is a very well-known fact that high selectivity will lead to conversion of more reactant into the product which will reduce the cost of the process at industrial scale.
In an embodiment, the present invention provides a process for preparation of dichloropyridine, having yield greater than 80 to 95%.
In an embodiment, the present invention provides a process for preparation of dichloropyridine, having purity greater than 97%, preferably greater than 98%, more preferably greater than 99%, having multi-chlorinated impurities in an amount of 0.01 to 0.5%.
In another embodiment of the present invention, the solvent used or generated in the reaction is recovered and recycled for subsequent reactions.
The aminochloropyridines used in the present invention may be prepared by any method known in the literature or may be obtained commercially.
The product may be isolated by any method known in the art, for example, chemical separation, extraction, acid-base neutralization, distillation, recrystallization, evaporation, column chromatography and filtration or a mixture thereof.
The completion of the reaction may be monitored by any one of chromatographic techniques such as thin layer chromatography (TLC), high pressure liquid chromatography (HPLC), ultra-pressure liquid chromatography (UPLC), Gas chromatography (GC), liquid chromatography (LC) and alike.
Unless stated to the contrary, any of the words “comprising”, “comprises” and includes mean “including without limitation” and shall not be construed to limit any general statement that it follows to the specific or similar items or matters immediately following it.
Embodiments of the invention are not mutually exclusive but may be implemented in various combinations. The described embodiments of the invention and the disclosed examples are given for the purpose of illustration rather than limitation of the invention as set forth in the appended claims.
The following example is given by way of illustration and therefore should not be construed to limit the scope of the present invention.

EXAMPLES
Example 1: Preparation of 2,3-dichloropyridine
A solution of 2-amino-3-chloropyridine (10%, 0.41 mol) in aqueous hydrochloric acid (25%; 0.40 mol) and an aqueous solution of sodium nitrite (40%, 0.57 mol) were simultaneously added to a continuous stirred reactor 1 at a flow rate of 4.41 g/min and 0.9 g/min respectively. The reaction mixture from continuous stirred reactor 1 was continuously added to continuous stirred reactor 2 containing a solution of sulfamic acid (3.88g, 0.04 mol), cuprous chloride (11.8g, 0.12 mol) and hydrochloric acid (35%; 130g 1.24 mol) at a temperature of 55°C for an hour. After completion of the reaction, the reaction mass was subjected to steam distillation, filtration, followed by crystallization to get the titled compound. (Yield: 92.0%).
Example 2: Preparation of 2,5-dichloropyridine
A solution of 2-amino-5-chloropyridine (10%, 0.41 mol) in aqueous hydrochloric acid (25%; 0.40 mol) and an aqueous solution of sodium nitrite (40%, 0.57 mol) were simultaneously added to a continuous stirred reactor 1 at a flow rate of 4.41 g/min and 0.9 g/min respectively. The reaction mixture from continuous stirred reactor 1 was continuously added to continuous stirred reactor 2 containing a solution of sulfamic acid (3.88g, 0.04 mol), cuprous chloride (11.8g, 0.12 mol) and hydrochloric acid (35%; 130g 1.24 mol) at a temperature of 55°C for an hour. After completion of the reaction, the reaction mass was subjected to steam distillation, filtration, followed by crystallization to get the titled compound. (Yield: 90.0%).
Example 3: Preparation of 2,3-dichloropyridine
A solution of 2-amino-3-chloropyridine (11.0%, 0.39 mol) in aqueous hydrochloric acid (30%; 0.40 mol) and an aqueous solution of sodium nitrite (40%, 0.54 mol) were added to a continuous stirred reactor 1 at a flow rate of 4.41 g/min and 0.9 g/min respectively. The reaction mixture from continuous stirred reactor 1 was continuously added to continuous stirred reactor 2 containing a solution of p-nitroaniline (5.52g, 0.04 mol), cuprous chloride (11.8g, 0.12 mol) and hydrochloric acid (35%; 130g 1.24 mol) at a temperature of 55°C for an hour. After completion of the reaction, the reaction mass was subjected to steam distillation, filtration, followed by crystallization to get the title compound (Yield: 91.0%).
Example 4: Preparation of 2,5-dichloropyridine
A solution of 2-amino-5-chloropyridine (11.5%, 0.40 mol) in aqueous hydrochloric acid (30%; 0.40 mol) and an aqueous solution of sodium nitrite (40%, 0.52 mol) were added to a continuous stirred reactor 1 at a flow rate of 4.41 g/min and 0.9 g/min respectively. The reaction mixture from continuous stirred reactor 1 was continuously added to continuous stirred reactor 2 containing a solution of urea (2.40g, 0.04 mol), cuprous chloride (11.8g, 0.12 mol) and hydrochloric acid (35%; 105.0g 1.006 mol) at a temperature of 55°C for an hour. After completion of the reaction, the reaction mass was subjected to steam distillation, filtration and followed by crystallization to get the titled compound. (Yield: 89.0%).
, Claims:WE CLAIM:

1. A process for preparation of dichloropyridine, comprising the steps of:
a) contacting a solution of 2-aminochloropyridine in hydrochloric acid with a diazotizing agent in a continuous stirred reactor 1;
b) quenching the diazotized mass of step a) with copper (I) salt in presence of a nitrous acid scavenger in another continuous stirred reactor 2;
c) isolating dichloropyridine.
2. The process as claimed in claim 1, wherein the dichloropyridine is selected from a group consisting of 2,3-dichloropyridine, 2,4-dichloropyridine, 2,5-dichloropyridine and 2,6-dichloropyridine.
3. The process as claimed in claim 1, wherein 2-aminochloropyridine is selected from a group consisting of 2-amino-3-chloropyridine, 2-amino-4-chloropyridine, 2-amino-5-chloropyridine and 2-amino-6-chloropyridine.
4. The process as claimed in claim 1, wherein the step a) and step b) are carried out in absence of any organic solvent.
5. The process as claimed in claim 1, wherein the diazotization agent is selected from a group consisting of sodium nitrite, potassium nitrite, t-butyl nitrite and nitrosyl sulfuric acid.
6. The process as claimed in claim 1, wherein the step of quenching is carried out using copper (I) salt, wherein copper (I) salt is copper (I) chloride, wherein copper (I) chloride is present in an amount of at least 50-90%.
7. The process as claimed in claim 1, wherein the solution of aminochloropyridine in hydrochloric acid is added to a continuous stirred reactor at a flow rate of 4.0 to 5.0g per minute.
8. The process as claimed in claim 1, wherein the aqueous solution of diazotizing agent is added to a continuous stirred reactor at a flow rate of 0.9g per minute to 1.5g per minute.
9. The process as claimed in claim 1, wherein the nitrous acid scavenger is selected from a group consisting of sulfamic acid, urea and p-nitroaniline.
10. The process as claimed in claim 1, wherein dichloropyridine contains 0.01 to 0.5%.of multi-chlorinated impurities selected from a group consisting of 2,3,4-trichloropyridine; 2,3,6-trichloropyridine, 2,3,5-trichloropyridine and 2,4,6-trichloropyridine.
Dated this 15th day of December 2022