EXTRACTED FROM WIPO

NOVEL PROCESSES FOR THE PREPARATION OF 2,3-DICHLORO-4- HYDROXYANILINE

FIELD OF THE INVENTION

The present invention relates to a novel process for the preparation of 2,3-dichloro-4-hydroxyaniline of formula I.

BACKGROUND

2,3-dichloro-4-hydroxyaniline of formula I is a key intermediate for the synthesis of several pharmaceutical, agrochemical, and other important fine chemical products.

For example, Fenhexamid is a systemic fungicide from the family of sterol biosynthesis inhibitors, and is prepared using 2,3-dichloro-4-hydroxyaniline of formula I

Several synthetic methods have been reported in literature to prepare 2,3-dichloro-4-hydroxyaniline of formula I

US5545754 discloses a process for the preparation of 2,3-dichloro-4-hydroxyaniline of formula I, which consists of reacting 2,3-dichloronitrobenzene of formula IP using 5% platinum/carbon (Pt/C), sulfuric acid, water, and methanol in the presence of hydrogen at a pressure of 10 bar and a temperature of 115°C. It also discloses the process for preparing 2,3-dichloro-4-hydroxyaniline of formula I wherein ethylene glycol is used instead of methanol as a solvent at 105°C and a pressure of 2.6 bar.

DEI 9804556 discloses a process for the preparation of 2,3-dichloro-4-hydroxyaniline of formula I, which consists of reacting 2,3-dichloronitrobenzene of formula III using 1% platinum/carbon (Pt/C), sulfuric acid, water and a mixture of methyl tert -butyl ether and toluene as a solvent in the presence of hydrogen at a pressure of 09 bar and a temperature of 95°C to 105°C. It also discloses a process for the preparation of 2,3-dichloro-4-hydroxyaniline of formula I using different solvents such as 1,2-dimethoxy ethanol, a mixture of xylene and tetrahydrofuran and a mixture of 1,2-dimethoxyethane and toluene.

CN110590570 discloses a process for the preparation of 2,3-dichloro-4-hydroxyaniline of formula I, which consists of reacting 2,3-dichloronitrobenzene of formula III using 1% platinum/carbon (Pt/C), sulfuric acid, water, cetyltrimethylammonium bromide (as a surfactant), 3-aminopyridine (as a co-catalyst) in the presence of hydrogen at a pressure of 10 bar and a temperature of 100°C.

The above patent documents do not provide a process for isolating and achieving more than 97% purity of the 2,3-dichloro-4-hydroxyaniline of formula I. These patent documents are silent on controlling or obviating impurities formed in the process and the purity of the isolated 2,3-dichloro-4-hydroxyaniline of formula I.

Additionally, the process disclosed in CN’570 involves the use of expensive surfactant and cocatalyst.

Therefore, there is a continuing need to develop a process for the preparation of 2,3-dichloro-4-hydroxyaniline of formula I which obviates at least one problem of prior art processes, such as impure 2,3-dichloro-4-hydroxyaniline of formula I, expensive surfactant/ co-catalyst and uncontrolled formation of impurities.

The inventors of the present invention provide a novel process for preparing 2,3-dichloro-4-hydroxyaniline of formula I which controls or obviates the formation of impurities. The process provided for the preparation of 2,3-dichloro-4-hydroxyaniline of formula I also employs economic reagents and is industrially amenable.

OBJECTS OF THE INVENTION

Some of the objects of the present invention are described herein below:

It is an object of the present invention to ameliorate one or more problems of the prior art or to at least provide a useful alternative.

An object of the present invention is to provide a process for the preparation of 2,3-dichloro-4-hydroxyaniline of formula I from 2,3-dichloronitrobenzene of formula III which employs economic reagents suitable for large scale batch production.

Another object of the present invention is to provide a process for the preparation of 2,3-dichloro-4-hydroxyaniline of formula I in which impurities are controlled or obviated.

Yet another object of the present invention is to provide a process for the preparation of 2,3-dichloro-4-hydroxyaniline of formula I at lower pressure and temperature.

Other objects and advantages of the present invention will be more apparent from the following description which is not intended to limit the scope of the present invention.

SUMMARY OF THE INVENTION

The present invention relates to the novel, efficient and industrially advantageous process for the preparation of 2,3-dichloro-4-hydroxyaniline of formula I.

A first aspect of the present invention provides a process for the preparation of 2,3-dichloro-4-hydroxyaniline of formula I comprising reacting 2,3-dichloronitrobenzene of formula III with hydrogen using aqueous sulfuric acid, one or more organic acid and a precious metal catalyst to obtain a reaction mixture comprising 2,3-dichloroaniline of formula II and 2,3-dichloro-4-hydroxyaniline of formula I.

Scheme - 1

A second aspect of the present invention provides a process for the preparation of 2,3-dichloro-4-hydroxyaniline of formula I comprising the steps of:

a) reacting 2,3-dichloronitrobenzene of formula III with hydrogen using aqueous sulfuric acid, one or more organic acid and a precious metal catalyst to obtain a reaction mixture comprising 2,3-dichloroaniline of formula II and 2,3-dichloro-4- hydroxyaniline of formula I;

b) obtaining a wet cake comprising the mixture of 2,3-dichloroaniline of formula II and 2,3-dichloro-4-hydroxyanibne of formula I in the ratio ranging from 1:0.2 to 1:4;

c) treating the mixture of 2,3-dichloroaniline of formula II and 2,3-dichloro-4- hydroxyaniline of formula I with charcoal or activated charcoal at 50°C to 150°C in the presence of a solvent, wherein the said solvent is a mixture of aromatic hydrocarbon and C1 to C4 alcohol; and

d) processing the mixture to obtain 2,3-dichloro-4-hydroxyaniline of formula I having purity 98% or more.

A third aspect of the present invention provides a process for purification of 2,3-dichloro-4-hydroxyaniline of formula I comprising the steps of:

a) treating the mixture of 2,3-dichloroaniline of formula II and 2,3-dichloro-4- hydroxyaniline of formula I in the ratio ranging from 1:0.2 to 1:4 with charcoal or activated charcoal at 50°C to 150°C in the presence of a solvent, wherein the said solvent is a mixture of aromatic hydrocarbon and C1 to C4 alcohol; and

b) processing the mixture to obtain 2,3-dichloro-4-hydroxyaniline of formula I having purity of 98% or more.

Scheme - IP

DETAILED DESCRIPTION OF THE INVENTION

The present invention discloses a process for the preparation of 2,3-dichloro-4-hydroxyaniline of formula I.

In accordance with the first aspect of the present invention there is provided a process for the preparation of 2,3-dichloro-4-hydroxyaniline of formula I, wherein 2,3-dichloronitrobenzene of formula III is reacted with hydrogen using aqueous sulfuric acid, one or more organic acid and a precious metal catalyst to obtain a reaction mixture comprising 2,3-dichloroaniline of formula II and 2,3-dichloro-4-hydroxyaniline of formula I.

The organic acid suitable for the reaction is selected from the group consisting of acetic acid, trifluoroacetic acid, methanoic acid, propionic acid, or mixtures thereof.

The molar ratio of 2,3-dichloronitrobenzene of formula III and the organic acid for the reaction is in the range of 1 : 0.1 to 1:0.5.

The precious metal catalyst suitable for the reaction is selected from the group consisting of platinum/carbon (Pt/C) or palladium/carbon (Pd/C).

The percentage of precious metal catalyst is 1% to 5% and loading catalyst is 0.08 to 0.3 w/w% with respect to 2,3-dichloronitrobenzene of formula III.

The molar ratio of 2,3-dichloronitrobenzene of formula III and sulfuric acid for the reaction is in the range of 1:2 to 1:3 and concentration of aqueous sulfuric acid for the reaction is in the range of 10% to 20%.

The reaction is carried out at a pressure ranging from 2 Kg/cm2 to 7 Kg/cm2.

The reaction is carried out at a temperature ranging from 20°C to 120°C.

After completion of the reaction, a reaction mixture is obtained which comprises 2,3-dichloroaniline of formula II and 2,3-dichloro-4-hydroxyaniline of formula I in the ratio ranging from 1:0.2 to 1:4.

Surprisingly, the mixture is at least substantially devoid of dehalogenated impurities selected from the group consisting of ortho- chloroaniline and m eta-chloroaniline.

In accordance with the second aspect of the present invention there is provided a process for the preparation of 2,3-dichloro-4-hydroxyaniline of formula I. The process is described herein after:

In step (a) 2,3-dichloronitrobenzene of formula III is reacted with hydrogen using aqueous sulfuric acid, one or more organic acid and a precious metal catalyst to obtain a reaction mixture comprising 2,3 -di chloroaniline of formula II and 2,3-dichloro-4-hydroxyaniline of formula I.

In step (b) a wet cake comprising the mixture of 2,3-dichloroaniline of formula II and 2,3-dichloro-4-hydroxyaniline of formula I in the ratio ranging from 1:0.2 to 1 :4 is obtained.

In step (c) the obtained mixture of 2,3-dichloroaniline of formula II and 2,3-dichloro-4-hydroxyaniline of formula I is treated with charcoal or activated charcoal at 50°C to 150°C in the presence of a solvent, wherein the said solvent is a mixture of aromatic hydrocarbon and C1 to C4 alcohol.

In step (d) the mixture is processed to obtain 2,3-dichloro-4-hydroxyaniline of formula I having purity 98% or more.

The organic acid suitable for the reaction used in the step (a) is selected from the group consisting of acetic acid, trifluoroacetic acid, methanoic acid, propionic acid, or mixtures thereof.

The molar ratio of 2,3-dichloronitrobenzene of formula IP and the organic acid for the reaction used in the step (a) is in the range of 1 :0.1 to 1:0.5.

The precious metal catalyst suitable for the reaction used in the step (a) is selected from the group consisting of platinum/carbon (Pt/C) or palladium/carbon (Pd/C).

The percentage of precious metal catalyst used in the step (a) is 1% to 5% and loading of the catalyst is 0.08 to 0.3 w/w% with respect to 2,3-dichloronitrobenzene of formula IP.

The molar ratio of 2,3-dichloronitrobenzene of formula IP and sulfuric acid for the reaction used in the step (a) is in the range of 1 : 2 to 1 : 3 and concentration of aqueous sulfuric acid for the reaction is in the range of 10% to 20%.

The reaction of the step (a) is carried out at a pressure ranging from 2 Kg/cm2 to 7 Kg/cm2.

The reaction of the step (a) is carried out at a temperature ranging from 20°C to 120°C.

After completion of the reaction of the step (a), a reaction mixture is obtained which comprises

2.3-dichloroaniline of formula II and 2,3-dichloro-4-hydroxyaniline of formula I in the ratio ranging from 1:0.2 to 1:4.

Surprisingly, the mixture is at least substantially devoid of dehalogenated impurities selected from the group consisting of ortho- chloroaniline and meta-chloroaniline.

In step (b), the reaction mixture obtained in step (a) is cooled to 10°C to 80°C and filtered to remove the catalyst to obtain a filtrate.

In the subsequent step, the filtrate is neutralized using a base and filtered to obtain a wet cake comprising 2,3-dichloroaniline of formula II and 2,3-dichloro-4-hydroxyaniline of formula I.

The base used in step (b) is selected from the group consisting of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, sodium hydroxide and potassium hydroxide.

In step (c), the resulting wet cake obtained in the step (b) comprising the mixture of 2,3-dichloroaniline of formula II and 2,3-dichloro-4-hydroxyaniline of formula I is purified to obtain

2.3-dichloro-4-hydroxyaniline of formula I having purity of 98% or more by treating the wet cake with charcoal or activated charcoal at 50°C to 150°C in the presence of a solvent, wherein the said solvent is a mixture of aromatic hydrocarbon and C1 to C4 alcohol.

The aromatic hydrocarbon used in the step (c) is selected from the group consisting of benzene, xylene such as o-xylene, m-xylene and p-xylene, a mixture of xylenes, and toluene.

The alcohol used in the step (c) is selected from the group consisting of C1 to C4 alcohol selected from the group consisting of methanol, ethanol, n-propanol, iso-propanol, n-butanol, sec-butanol, iso-butanol and tert-butanol.

In step (d), the resulting mixture of the wet cake and the solvent is processed to obtain 2,3-dichloro-4-hydroxyaniline of formula I having purity 98% or more.

The processing of the said resulting mixture includes cooling, distillation, drying, crystallization or precipitation, recrystallization and filtration.

2,3-dichloro-4-hydroxyaniline of formula I can be repeatedly purified by the same process to obtain 2,3-dichloro-4-hydroxyaniline of formula I having purity 98% or more.

In accordance with the third aspect of the present invention, 2,3-dichloro-4-hydroxyaniline of formula I is purified to obtain 2,3-dichloro-4-hydroxyaniline of formula I having purity of 98%.

A mixture of 2,3-dichloroaniline of formula II and 2,3-dichloro-4-hydroxyaniline of formula I in the ratio ranging from 1:0.2 to 1:4 is purified to obtain 2,3-dichloro-4-hydroxyaniline of formula I having purity of 98% or more by treating the mixture with charcoal or activated charcoal at 50°C to 150°C in the presence of a solvent, wherein the said solvent is a mixture of aromatic hydrocarbon and C1 to C4 alcohol.

The aromatic hydrocarbon is selected from the group consisting of benzene, xylene such as o-xylene, m-xylene and p-xylene, a mixture of xylenes and toluene.

The alcohol is selected from the group consisting of C1 to C4 alcohol selected from the group consisting of methanol, ethanol, n-propanol, iso-propanol, n-butanol, .vcc-butanol, iso-butanol and /c/7-butanol.

The resulting mixture of the wet cake and the solvent is processed to obtain 2,3-dichloro-4-hydroxyaniline of formula I having purity 98% or more.

The processing of the said resulting mixture includes cooling, distillation, drying, crystallization or precipitation, recrystallization and filtration.

2,3-dichloro-4-hydroxyaniline of formula I can be repeatedly purified by the same purification process to obtain 2,3-dichloro-4-hydroxyaniline of formula I with further enhanced purity.

The process of the present invention for the preparation of 2,3-dichloro-4-hydroxyaniline of formula I having purity 98% or more is a single or multi pot process.

2,3-dichloro-4-hydroxyaniline of formula I can be used as a key starting material or as an intermediate in preparing Active Pharmaceutical Ingredients. If 2,3-dichloro-4-hydroxyaniline of formula I contains impurities they may get carried forward to a final Active Pharmaceutical Ingredient (API) or may react to form other by-products.

Such impurities may be unreacted starting materials, by-products of the reaction, products of side reactions, or degradation products or different isomers. Impurities generated due to any reason in any API are undesirable and, in extreme cases, might even be harmful to a patient being treated with a dosage form containing the API.

The American Food and Drug Administration (FDA) as well as European medicament control offices require, according to the Q7A ICH (International Conference on Harmonization) guidance, that Active Pharmaceutical Ingredient (API) is free of impurities to the maximum possible extent. The reason being achieving maximum safety of using the drug in clinical practice.

It is usually required that the content of an individual impurity in an API should not exceed the limit of 0.1%. All the substances (generally referred to as impurities) contained in an API over the limit of 0.1% should be isolated and characterized in accordance with the ICH recommendations. Q7A ICH guidance for manufacturers also states that process impurities be maintained below set limits by specifying the quality of raw materials, controlling process parameters, such as temperature, pressure, time and stoichiometric ratio, and including purification steps, such as crystallization, distillation, and liquid-liquid extraction, in the manufacturing process.

It is always advantageous to use an intermediate of high purity which is free from the undesired impurities or such impurities should be present in acceptable amounts. The purity of the chemical compounds can be measured by chromatographic techniques such as high pressure liquid chromatography (HPLC) or by gas chromatography (GC).

As most of the prior art references are silent about purity of the 2,3-dichloro-4-hydroxyaniline of formula I and content of impurities and have certain other disadvantages the present invention provides a process for the preparation of 2,3-dichloro-4-hydroxyaniline of formula I wherein the formation of impurities is reduced or obviated.

Various features and embodiments of the present invention are illustrated in the following representative examples, which are intended to be illustrative and non-limiting.

EXAMPLES:

Example 1: Preparation of 2,3-dichloro-4-hydroxyaniline of formula I

2,3-dichloronitrobenzene of formula IP (13 Kg) was slowly added to aqueous sulphuric acid (127 Kg) at room temperature. Methanoic acid and 3% platinum/carbon (15.6 g) were added to the resulting mixture at room temperature. Hydrogen gas was then passed to the resulting mixture at a pressure of 4 Kg/cm2 and temperature was increased to 115°C. The reaction mixture was maintained at 115°C till the consumption of hydrogen stopped. After completion of the reaction, the resulting mixture was cooled to room temperature and filtered. The resulting filtrate was neutralized using sodium carbonate and filtered to obtain a wet cake (11.0 Kg) comprising a mixture of 2,3-dichloroaniline of formula II and 2,3-dichloro-4-hydroxyaniline of formula I in the ratio 1:0.35.

Purity: 2,3-dichloroaniline 69.94%, 2,3-dichloro-4-hydroxyaniline 24.95%

To a stirred solution of toluene and methanol, the wet cake followed by charcoal was added. The resulting mixture was heated to a clear solution and stirred for 30 minutes at the same temperature. The mixture was then processed to obtain pure 2,3-dichloro-4-hydroxyaniline of formula I.

Purity: 2,3-dichloro-4-hydroxyaniline 99.10%.

Example 2: Preparation of 2,3-dichloro-4-hydroxyaniline of formula I

2,3-dichloronitrobenzene of formula IP (13 Kg) was slowly added to aqueous sulphuric acid (127 Kg) at room temperature. Methanoic acid and 3% platinum/carbon (15.6 g) were added to the resulting mixture at room temperature. Hydrogen gas was then passed to the resulting mixture at a pressure of 4 Kg/cm2 and temperature was increased to 80°C. The reaction mixture was maintained at 80°C till the consumption of hydrogen stopped. After completion of the reaction, the resulting mixture was filtered at 80°C. The resulting filtrate was neutralized using sodium carbonate and filtered to obtain a wet cake (11.0 Kg) comprising a mixture of 2,3-dichloroaniline of formula II and 2,3-dichloro-4-hydroxyaniline of formula I in the ratio 1:1.2.

Purity: 2,3-dichloroaniline 43.58%, 2,3-dichloro-4-hydroxyaniline 52.49%.

To a stirred solution of toluene and methanol, the wet cake followed by charcoal was added. The resulting mixture was heated to a clear solution and stirred for 30 minutes at the same temperature. The mixture was then processed to obtain pure 2,3-dichloro-4-hydroxyaniline of formula I.

Purity: 2,3-dichloro-4-hydroxyaniline 99.30%.

Example 3: Preparation of 2,3-dichloro-4-hydroxyaniline of formula I

2,3-dichloronitrobenzene of formula IP (13 Kg) was slowly added to aqueous sulphuric acid (127 Kg) at room temperature. Methanoic acid and 3% platinum/carbon (15.6 g) were added to the resulting mixture at room temperature. Hydrogen gas was then passed to the resulting mixture at a pressure of 4 Kg/cm2 and temperature was increased to 80°C. The reaction mixture was maintained at 80°C till the consumption of hydrogen stopped. After completion of the reaction, the resulting mixture was cooled to room temperature and filtered. The resulting filtrate was neutralized using sodium carbonate and filtered to obtain a wet cake (11.0 Kg) comprising a mixture of 2,3-dichloroaniline of formula II and 2,3-dichloro-4-hydroxyaniline of formula I in the ratio 1:0.35.

Purity: 2,3-dichloroaniline 69.10%, 2,3-dichloro-4-hydroxyaniline 24.81%.

To a stirred solution of toluene and ethanol, the wet cake followed by charcoal was added. The resulting mixture was heated to a clear solution and stirred for 30 minutes at the same temperature. The mixture was then processed to obtain pure 2,3-dichloro-4-hydroxyaniline of formula I.

Purity: 2,3-dichloro-4-hydroxyaniline 99.00%.

Example 4: Preparation of 2,3-dichloro-4-hydroxyaniline

2,3-dichloronitrobenzene (131 g) was slowly added to aqueous sulphuric acid (1279.82 g) at room temperature. Methanoic acid (5.3 g) and 3% platinum/carbon (0.35 g) were added to the resulting mixture at room temperature. Hydrogen gas was then passed to the resulting mixture at a pressure of 4 Kg/cm2 and temperature was increased to 80°C. The reaction mixture was maintained at 70°C to 80°C till the consumption of hydrogen stopped. After completion of the reaction, the resulting mixture filtered at 80°C. The resulting filtrate was neutralized at 80°C using sodium carbonate and filtered to obtain a wet cake (11 g) comprising a mixture of 2,3-dichloroaniline and 2,3-dichloro-4-hydroxyaniline in the ratio 1:1.2.

CLAIMS

1. A process for the preparation of 2,3-dichloro-4-hydroxyaniline of formula I;

said process comprising;

reacting 2,3-dichloronitrobenzene of formula III,

with hydrogen using aqueous sulfuric acid, one or more organic acids and a precious metal catalyst to obtain a reaction mixture comprising 2,3-dichloroaniline of formula II and 2,3- dichloro-4-hydroxyaniline of formula I.

2. A process for preparation of 2,3-dichloro-4-hydroxyaniline of formula I;

said process comprising the steps of:

a) reacting 2,3-dichloronitrobenzene of formula III,

with hydrogen using aqueous sulfuric acid, one or more organic acid and a precious metal catalyst to obtain a first reaction mixture comprising 2,3-dichloroaniline of formula II and 2,3-dichloro-4-hydroxyaniline of formula I;

b) obtaining a wet cake comprising the mixture of 2,3-dichloroaniline of formula II and 2,3-dichloro-4-hydroxyaniline of formula I in the ratio ranging from 1:0.2 to 1 :4 from the first reaction mixture I obtained in step (a);

c) treating the mixture of 2,3-dichloroaniline of formula II and 2,3-dichloro-4- hydroxyaniline of formula I obtained in step (b) with charcoal or activated charcoal at 50°C to 150°C in the presence of a solvent, wherein the said solvent is a mixture of aromatic hydrocarbon and C1 to C4 alcohol to obtain a second reaction mixture; and

d) processing the second reaction mixture obtained in step (c) to obtain 2,3-dichloro- 4-hydroxyaniline of formula I.

3. A process for purification of 2,3-dichloro-4-hydroxyaniline of formula I comprising the steps of:

a) treating the mixture of 2,3-dichloroaniline of formula II and 2,3-dichloro-4- hydroxyaniline of formula I with charcoal or activated charcoal at 50°C to 150°C in the presence of a solvent, wherein the said solvent is a mixture of aromatic hydrocarbon and C1 to C4 alcohol to obtain reaction mixture; and

b) processing the reaction mixture as obtained in step (a) to obtain 2,3-dichloro-4- hydroxyaniline of formula I.

4. The process as claimed in the claim 1 and 2, wherein the organic acid used is selected from the group consisting of acetic acid, trifluoroacetic acid, methanoic acid, propionic acid or mixtures thereof.

5. The process as claimed in the claim 1 and 2, wherein the molar ratio of 2,3- dichloronitrobenzene of formula III and the organic acid ranges from 1:0.1 to 1:0.5.

6. The process as claimed in the claim 1 and 2, wherein the precious metal catalyst used is selected from the group consisting of platinum/carbon (Pt/C) or palladium/carbon (Pd/C).

7. The process as claimed in the claim 1 and 2, wherein the percentage of the precious metal catalyst is 1 to 5 % and loading of the metal catalyst is 0.08 to 0.3 w/w% with respect to

2,3-dichloronitrobenzene of formula III.

8. The process as claimed in the claim 1 and 2, wherein the molar ratio of 2,3- dichloronitrobenzene of formula IP and aqueous sulphuric acid used ranges from 1:2 to 1:3.

9. The process as claimed in the claim 1 and 2, wherein the concentration of aqueous sulfuric acid ranges from 10% to 20%.

10. The process as claimed in the claim 1 and 2, wherein the reaction is carried out at temperatures ranging from 20°C to 120°C.

11. The process as claimed in the claim 1 and 2, wherein the reaction is carried out at pressure ranging from 2 Kg/cm2 to 7 Kg/cm2.

12. The process as claimed in the claim 2, wherein the step (b) is carried out by cooling the reaction mixture obtained from step (a) to 10°C to 80°C, filtering, neutralizing the obtained filtrate with a suitable base and filtering to obtain the wet cake.

13. The process as claimed in the claim 12, wherein the suitable base selected from the group consisting of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, sodium hydroxide and potassium hydroxide.

14. The process as claimed in the claim 2 and 3, wherein aromatic hydrocarbon is selected from the group consisting of benzene, o-xylene, m-xylene and p-xylene, toluene or mixtures thereof.

15. The process as claimed in the claim 2 and 3, wherein C1 to C4 alcohol is selected from the group consisting of methanol, ethanol, n-propanol, iso-propanol, n-butanol, sec-butanol, iso-butanol and tert-butanol.

16. The process as claimed in the claim 2, wherein the process step (d) is carried by at least one or more method selected from cooling, distillation, drying, crystallization, precipitation, recrystallization and filtration.