Claims:FORM-2
THE PATENTS ACT, 1970
(39 of 1970)
AND
THE PATENTS RULES, 2003

COMPLETE
SPECIFICATION
(See section 10; rule 13)

PROCESS FOR THE PREPARATION OF 3-(3,4-DICHLOROPHENYL)-1,1-DIMETHYLUREA

GHARDA CHEMICALS LIMITED
an Indian company of,
D-1/2 Midc Lote Parshuram, Khed Taluka, Ratnagiri District,
Pin Code - 415722 Maharashtra, India

THE FOLLOWING SPECIFICATION PARTICULARLY DESCRIBES THE INVENTION AND THE MANNER IN WHICH IT IS TO BE PERFORMED.

FIELD
The present disclosure relates to a process for the preparation of 3-(3,4-dichlorophenyl)-1,1-dimethylurea.
BACKGROUND
3-(3,4-dichlorophenyl)-1,1-dimethylurea is a phenylurea derivative and is used as an herbicidal agent.

3-(3,4-dichlorophenyl)-1,1-dimethylurea
Conventionally a process for the preparation of 3-(3,4-dichlorophenyl)-1,1-dimethylurea is known in the art, in which reaction of urea, dichloroaniline, and dimethylamine in ortho dichlorobenzene with the removal of ammonia provides 3-(3,4-dichlorophenyl)-1,1-dimethylurea. These reactants used in the aforestated process are expensive and need to be used in excess. Further, the reaction between urea and dichloroaniline results in large amount of impurities which are difficult to remove from the product mixture. The yield/productivity of 3-(3,4-dichlorophenyl)-1,1-dimethylurea, obtained from the known processes is considerably low.
There is, therefore, felt a need to provide a simple, efficient and economical process for the preparation of 3-(3,4-dichlorophenyl)-1,1-dimethylurea.

OBJECTS
Some of the objects of the present disclosure, which at least one embodiment herein satisfies, are as follows.
It is an object of the present disclosure to ameliorate one or more problems of the prior art or to at least provide a useful alternative.
An object of the present disclosure is to provide a simple and efficient process for preparing 3-(3,4-dichlorophenyl)-1,1-dimethylurea.
Another object of the present disclosure is to provide an economical process for preparing 3-(3,4-dichlorophenyl)-1,1-dimethylurea with comparatively high yield and high purity.
Other objects and advantages of the present disclosure will be more apparent from the following description, which is not intended to limit the scope of the present disclosure.
SUMMARY
The present disclosure relates to a process for preparing 3-(3,4-dichlorophenyl)-1,1-dimethylurea. The process comprises mixing 3,4-dichloroaniline, at least one first fluid media, and optionally at least one base to obtain a first mixture. The first mixture is reacted with methyl haloformate under stirring, at a temperature in the range of 15 °C to 60 °C to obtain a second mixture comprising methyl N-(3,4-dichlorophenyl)carbamate. The second mixture is allowed to settle to obtain a biphasic mixture comprising an organic layer and an aqueous layer. The aqueous layer is separated from the biphasic mixture to obtain the organic layer, followed by azeotropic dehydration of the organic layer to obtain an anhydrous organic layer comprising methyl N-(3,4-dichlorophenyl)carbamate. The methyl N-(3,4-dichlorophenyl)carbamate present in anhydrous organic layer is reacted with dimethyl amine at a temperature in the range of 120 °C to 140 °C with continuous removal of methanol to obtain a product mixture comprising 3-(3,4-dichlorophenyl)-1,1-dimethylurea. The product mixture is cooled at a temperature in the range of 10 °C to 25 °C to obtain a slurry. The so formed slurry is filtered to obtain a solid mass, followed by washing with at least one second fluid media, and drying the solid mass to obtain 3-(3,4-dichlorophenyl)-1,1-dimethylurea having purity greater than 98 %.
DETAILED DESCRIPTION
Different processes for the preparation of 3-(3,4-dichlorophenyl)-1,1-dimethylurea are known in the art. The reactants used to prepare 3-(3,4-dichlorophenyl)-1,1-dimethylurea are expensive and also the yield of the resultant 3-(3,4-dichlorophenyl)-1,1-dimethylurea, that is obtained from these known processes, is considerably low. Hence, the overall process, for the preparation of 3-(3,4-dichlorophenyl)-1,1-dimethylurea, is uneconomical.
The present disclosure envisages a process for the preparation of 3-(3,4-dichlorophenyl)-1,1-dimethylurea to mitigate the drawbacks mentioned herein above.
In accordance with the present disclosure, a process for the preparation of 3-(3,4-dichlorophenyl)-1,1-dimethylurea is provided. The process for the preparation of 3-(3,4-dichlorophenyl)-1,1-dimethylurea comprises the following steps.
In a first step, 3,4-dichloroaniline, at least one first fluid media, and optionally at least one base are mixed to obtain a first mixture.
In accordance with the embodiments of present disclosure, the base can be at least one selected from the group consisting of sodium bicarbonate, sodium hydroxide, sodium carbonate, potassium bicarbonate, potassium carbonate, potassium hydroxide, triethylamine, and trimethylamine. The base may be used to neutralize or remove any trapped acidity in the reaction mixture.
The molar ratio of 3,4-dichloroaniline to the base can be in the range of 1:1 to 1:1.5.
In accordance with one embodiment of the present disclosure, the molar ratio of 3,4-dichloroaniline to the base is 1:1.1.
The first fluid media is at least one selected from the group consisting of mono chlorobenzene, toluene, xylene, bromobenzene, ortho dichlorobenzene, and water.
In a second step, the first mixture is reacted with methyl haloformate under stirring, at a temperature in the range of 15 °C to 60 °C to obtain a second mixture comprising methyl N-(3,4-dichlorophenyl)carbamate.
The methyl haloformate can be at least one selected from the group consisting of methyl chloroformate, methyl bromoformate, methyl iodoformate, and methyl fluoroformate.
The molar ratio of 3,4-dichloroaniline to methyl haloformate can be in the range of 1:1.5 to 1:0.5.
In accordance with one embodiment of the present disclosure, the molar ratio of 3,4-dichloroaniline to methyl chloroformate is 1:1.2.
In a third step, the so formed second mixture is allowed to settle to obtain a biphasic mixture comprising an organic layer and an aqueous layer, followed by separating aqueous layer from the biphasic mixture to obtain the organic layer.
In accordance with one embodiment of the present disclosure, the methyl N-(3,4-dichlorophenyl)carbamate can be prepared by separating an aqueous layer from the biphasic mixture to obtain the organic layer, followed by washing with at least one base to remove any trapped acidity.
In the fourth step, the organic layer obtained in third step is azeotropically dehydrated to remove the moisture trapped in the organic layer and to obtain an anhydrous organic layer comprising methyl N-(3,4-dichlorophenyl)carbamate.
In accordance with one embodiment of the present disclosure, methyl N-(3,4-dichlorophenyl)carbamate can be separated from the organic layer.
In the fifth step, the methyl N-(3,4-dichlorophenyl)carbamate present in the anhydrous organic layer is reacted with dimethyl amine, at a temperature in the range of 120 °C to 140 °C with continuous removal of methanol to obtain a product mixture comprising 3-(3,4-dichlorophenyl)-1,1-dimethylurea.
The molar ratio of methyl N-(3,4-dichlorophenyl)carbamate to dimethylamine is in the range of 1:1.1 to 1:1.5.
In the sixth step, the product mixture is cooled at a temperature in the range of 10 °C to 25 °C to obtain a slurry.
In the seventh step, the slurry is filtered to obtain a solid mass, followed by washing with at least one second fluid media, and drying the solid mass to obtain 3-(3,4-dichlorophenyl)-1,1-dimethylurea having purity greater than 98 %.
The second fluid media is at least one selected from the group consisting of mono chlorobenzene, toluene, xylene, bromobenzene, and ortho dichlorobenzene.
The process of the present disclosure can be a one-pot reaction to prepare 3-(3,4-dichlorophenyl)-1,1-dimethylurea with high yield and high purity. The process is simple and efficient as the by-product such as methanol obtained by the process can be reused. Therefore, the process of the present disclosure to prepare 3-(3,4-dichlorophenyl)-1,1-dimethylurea is economical.
The present disclosure is further described in light of the following experiments which are set forth for illustration purpose only and not to be construed for limiting the scope of the disclosure. The following experiments can be scaled up to industrial/commercial scale and the results obtained can be extrapolated to industrial scale.
EXPERIMENT
Example 1: Process for preparation of 3-(3,4-dichlorophenyl)-1,1-dimethylurea in accordance with the process of the present disclosure.
Experiment 1:
300 ml of mono chlorobenzene and 250 ml of water were charged in a reactor with a central vertical stirrer, condenser and collection system to obtain a mixture. To this mixture, 162 g of 3,4-dichloroaniline were added to obtain a first mixture. The first mixture was stirred and reacted with 113.4 g of methyl chloroformate while controlling the temperature at 30 °C to obtain a second mixture containing methyl N-(3,4-dichlorophenyl)carbamate. Further, the second mixture was heated to 75 °C to obtain a biphasic mixture containing an organic layer and an aqueous layer. The aqueous layer was separated from the biphasic mixture to obtain the organic layer. The so formed organic layer was washed with 100 ml of 5 % sodium bicarbonate to remove any trap acidity, followed by azeotropic dehydration to remove trapped moisture to obtain methyl N-(3,4-dichlorophenyl)carbamate in organic phase. To this methyl N-(3,4-dichlorophenyl)carbamate, 56.25 g of dimethyl amine was passed at 130 °C with continuous removal of methanol to obtain a product mixture containing 3-(3,4-dichlorophenyl)-1,1-dimethylurea. The so formed product mixture was cooled to 20 °C to obtain a slurry. The slurry was filtered to obtain a product. The product was washed with 50 ml of mono chlorobenzene, followed by drying to obtain 3-(3,4-dichlorophenyl)-1,1-dimethylurea (yield = 92 %, HPLC purity= 99 %).

Experiment 2:
The process for the preparation of 3-(3,4-dichlorophenyl)-1,1-dimethylurea was similar to Experiment 1, except the organic solvent used in Experiment 2 was ortho dichlorobenzene (100 ml) instead of mono chlorobenzene. The yield of 3-(3,4-dichlorophenyl)-1,1-dimethylurea was 94 % and HPLC purity was 99.3 %.
Experiment 3:
The process for the preparation of 3-(3,4-dichlorophenyl)-1,1-dimethylurea was similar to Experiment 1, except the methyl haloformate used in Experiment 3 was methyl bromoformate (166.73 g) instead of methyl chloroformate. The results of Experiment 3 are found to be similar to Experiment 1.
The Experiment 1, Experiment 2, and Experiment 3 clearly indicate that the use of 3,4-dichloroaniline, methyl haloformate, and dimethylamine using afore-stated reaction process results in 3-(3,4-dichlorophenyl)-1,1-dimethylurea with high yields (> 90%) and high purity (= 99 %). The process also produces methanol as a by-product which can be reused. Also, it is a one-pot reaction and employs readily available reactants, hence the process for the preparation of 3-(3,4-dichlorophenyl)-1,1-dimethylurea is simple, efficient and economical.
Example 2: Process for the preparation of 3-(3,4-dichlorophenyl)-1,1-dimethylurea using two-step reaction.
Step I: Preparation and separation of methyl N-(3,4-dichlorophenyl)carbamate as an intermediate.
Experiment 4:
300 ml of mono chlorobenzene and 250 ml of water were charged into a reactor having central vertical stirrer, condenser and collection system to obtain a mixture. To this mixture, 162 g of 3,4-dichloroaniline and 100.8 g of sodium bicarbonate were added to obtain a first mixture. The first mixture was stirred and reacted with 113.4 g of methyl chloroformate while controlling the temperature at 30 °C to obtain a second mixture containing methyl N-(3,4-dichlorophenyl)carbamate. Further, the second mixture was heated to 75 °C to obtain a biphasic mixture containing an organic layer and an aqueous layer. The aqueous layer was separated from the biphasic mixture to obtain the organic layer, containing methyl N-(3,4-dichlorophenyl)carbamate. The so formed organic layer was cooled to 15 °C to obtain a slurry. The slurry was filtered to obtain a product. The product was washed with 50 ml of mono chlorobenzene, followed by drying to obtain methyl N-(3,4-dichlorophenyl)carbamate (yield = 90 %, HPLC purity= 100 %).
Experiment 5:
300 ml of mono chlorobenzene and 250 ml of water were charged into a reactor having central vertical stirrer, condenser and collection system to obtain a mixture. To this mixture, 162 g of 3,4-dichloroaniline and 100.8 g of sodium bicarbonate were added to obtain a first mixture. The first mixture was stirred and reacted with 113.4 g of methyl chloroformate while controlling the temperature at 30 °C to obtain a second mixture containing methyl N-(3,4-dichlorophenyl)carbamate. Further, the second mixture was heated to 75 °C to obtain a biphasic mixture containing an organic layer and an aqueous layer. The aqueous layer was separated from the biphasic mixture to obtain the organic layer, containing methyl N-(3,4-dichlorophenyl)carbamate. Further, mono chlorobenzene was evaporated to obtain methyl N-(3,4-dichlorophenyl)carbamate (yield = 99.5 %, HPLC purity= 99.8 %).
Experiment 6:
The process for the preparation of methyl N-(3,4-dichlorophenyl)carbamate was similar to Experiment 5, except the organic solvent and base used in Experiment 6 was ortho dichlorobenzene (300 ml) instead of mono chlorobenzene and 4 N sodium hydroxide solution (300 ml) instead of sodium bicarbonate respectively. The yield of methyl N-(3,4-dichlorophenyl)carbamate was 99 % and HPLC purity was 100 %.
Experiment 7:
500 ml of mono chlorobenzene and 162 g of 3,4-dichloroaniline were charged into a reactor having central vertical stirrer, condenser and collection system to obtain a mixture. The mixture was stirred and reacted with 113.4 g of methyl chloroformate while controlling the temperature at 30 °C to obtain a first mixture containing methyl N-(3,4-dichlorophenyl)carbamate. The first mixture was heated to 130 °C and maintained for 4 hours to obtain a clear solution and no more HCl evolution. Further, this first mixture was heated to 75 °C, followed by washing with 100 ml of 5 % sodium bicarbonate solution which removes any trapped acidity to obtain a biphasic mixture containing an organic layer and an aqueous layer. The aqueous layer was separated from the biphasic mixture to obtain the organic layer, containing methyl N-(3,4-dichlorophenyl)carbamate. Further, mono chlorobenzene was evaporated to obtain methyl N-(3,4-dichlorophenyl)carbamate (yield = 99 %, HPLC purity= 100 %).
Experiment 8:
300 ml of mono chlorobenzene and 250 ml of water were charged into a reactor having central vertical stirrer, condenser and collection system to obtain a mixture. To this mixture, 162 g of 3,4-dichloroaniline was added to obtain a first mixture. The first mixture was stirred and reacted with 166.73 g of methyl bromoformate while controlling the temperature at 40 °C to obtain a second mixture containing methyl N-(3,4-dichlorophenyl)carbamate. Further, the second mixture was heated to 75 °C to obtain a biphasic mixture containing an organic layer and an aqueous layer. The aqueous layer was separated from the biphasic mixture to obtain the organic layer, containing methyl N-(3,4-dichlorophenyl)carbamate, followed by washing with 100 ml of 5 % sodium bicarbonate solution to remove trapped acidity. Further, mono chlorobenzene was evaporated to obtain methyl N-(3,4-dichlorophenyl)carbamate (yield = 99.5 %, HPLC purity= 100 %).
The Experiments 4 to 8 clearly indicate that the use of methyl chloroformate and/or methyl bromoformate and 3,4-dichloroaniline using the afore-stated reaction process results in methyl N-(3,4-dichlorophenyl)carbamate, which is separated as an intermediate, with high yield and high purity.
Step II: Process for the preparation of 3-(3,4-dichlorophenyl)-1,1-dimethylurea from methyl N-(3,4-dichlorophenyl)carbamate obtained from Experiments 4 to 8.
Experiment 9:
300 ml of mono chlorobenzene and 220 g of methyl N-(3,4-dichlorophenyl)carbamate were charged in a reactor with central vertical stirrer, condenser and collection system to obtain a mixture. The so formed mixture was stirred and heated to 130 °C. To this mixture, 56.25 g of dimethylamine was passed with continuous removal of methanol to obtain a product mixture containing 3-(3,4-dichlorophenyl)-1,1-dimethylurea. The so formed product mixture was cooled to 20 °C to obtain a slurry. The slurry was filtered to obtain a product. The product was washed with 50 ml of mono chlorobenzene, followed by drying to obtain 3-(3,4-dichlorophenyl)-1,1-dimethylurea (yield = 91 %, HPLC purity= 99.2 %).
Experiment 10:
300 ml of mono chlorobenzene and 220 g of methyl N-(3,4-dichlorophenyl)carbamate were charged in a reactor with central vertical stirrer, condenser and collection system to obtain a mixture. The so formed mixture was stirred and heated to 130 °C. To this mixture, 56.25 g of dimethylamine was passed with continuous removal of methanol by controlling pressure at 0.8 kg/cm2 to obtain a product mixture containing 3-(3,4-dichlorophenyl)-1,1-dimethylurea. The so formed product mixture was cooled to 20 °C to obtain a slurry. The slurry was filtered to obtain a product. The product was washed with 50 ml of mono chlorobenzene, followed by drying to obtain 3-(3,4-dichlorophenyl)-1,1-dimethylurea (yield = 80 %, HPLC purity= 99.5 %).
The Experiment 9 and Experiment 10 clearly indicate that the use of methyl N-(3,4-dichlorophenyl)carbamate and diethylamine using afore-stated reaction process results in 3-(3,4-dichlorophenyl)-1,1-dimethylurea with high yields (> 80 %) and high purity (> 99 %). The process to prepare 3-(3,4-dichlorophenyl)-1,1-dimethylurea also produces methanol as a by-product which can be reused. However, the yield of 3-(3,4-dichlorophenyl)-1,1-dimethylurea obtained by using Experiment 10 is comparably low as reaction is carried out at controlled pressure, compared to the yield of 3-(3,4-dichlorophenyl)-1,1-dimethylurea obtained by using Experiment 9. Overall, the process to prepare 3-(3,4-dichlorophenyl)-1,1-dimethylurea is simple, efficient and economical.
TECHNICAL ADVANCES AND ECONOMICAL SIGNIFICANCE
The present disclosure, described herein above has several technical advantages including, but not limited to, the realization of a process for the preparation of 3-(3,4-dichlorophenyl)-1,1-dimethylurea, wherein the process:
- is simple and efficient;
- is economical; and
- provides comparatively high yield and high purity of 3-(3,4-dichlorophenyl)-1,1-dimethylurea.
Throughout this specification the word “comprise”, or variations such as “comprises” or “comprising”, will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.
The use of the expression “at least” or “at least one” suggests the use of one or more elements or ingredients or quantities, as the use may be in the embodiment of the disclosure to achieve one or more of the desired objects or results.
Any discussion of documents, acts, materials, devices, articles or the like that has been included in this specification is solely for the purpose of providing a context for the disclosure. It is not to be taken as an admission that any or all of these matters form a part of the prior art base or were common general knowledge in the field relevant to the disclosure as it existed anywhere before the priority date of this application.
The numerical values mentioned for the various physical parameters, dimensions or quantities are only approximations and it is envisaged that the values higher/lower than the numerical values assigned to the parameters, dimensions or quantities fall within the scope of the disclosure, unless there is a statement in the specification specific to the contrary.
While considerable emphasis has been placed herein on the components and component parts of the preferred embodiments, it will be appreciated that many embodiments can be made and that many changes can be made in the preferred embodiments without departing from the principles of the disclosure. These and other changes in the preferred embodiment as well as other embodiments of the disclosure will be apparent to those skilled in the art from the disclosure herein, whereby it is to be distinctly understood that the foregoing descriptive matter is to be interpreted merely as illustrative of the disclosure and not as a limitation.

WE CLAIM
1. A process for preparing 3-(3,4-dichlorophenyl)-1,1-dimethylurea, said process comprising:

i. mixing 3,4-dichloroaniline, at least one first fluid media, and optionally at least one base to obtain a first mixture;

ii. reacting said first mixture with methyl haloformate under stirring, at a temperature in the range of 15°C to 60°C to obtain a second mixture comprising methyl N-(3,4-dichlorophenyl)carbamate;

iii. allowing said second mixture to settle to obtain a biphasic mixture comprising an organic layer and an aqueous layer, followed by separating said aqueous layer from said biphasic mixture to obtain said organic layer;

iv. azeotropically dehydrating said organic layer to obtain an anhydrous organic layer comprising said methyl N-(3,4-dichlorophenyl)carbamate;

v. reacting said methyl N-(3,4-dichlorophenyl)carbamate obtained in step (iv) with dimethyl amine, at a temperature in the range of 120 °C to 140 °C with continuous removal of methanol to obtain a product mixture comprising 3-(3,4-dichlorophenyl)-1,1-dimethylurea;

vi. cooling said product mixture at a temperature in the range of 10 °C to 25 °C to obtain a slurry; and

vii. filtering said slurry to obtain a solid mass, followed by washing with at least one second fluid media, and drying said solid mass to obtain 3-(3,4-dichlorophenyl)-1,1-dimethylurea having purity greater than 98%.

2. The process as claimed in claim 1, wherein step (iii) optionally comprises washing of said organic layer with said at least one base.

3. The process as claimed in claim 1, wherein said base is at least one selected from the group consisting of sodium bicarbonate, sodium hydroxide, potassium bicarbonate, potassium carbonate, potassium hydroxide, sodium carbonate, triethylamine, and trimethylamine.

4. The process as claimed in claim 1, wherein said first fluid media are at least one selected from the group consisting of mono chlorobenzene, ortho dichlorobenzene, toluene, xylene, bromobenzene, and water.

5. The process as claimed in claim 1, wherein said second fluid media are at least one selected from the group consisting of mono chlorobenzene, ortho dichlorobenzene, toluene, xylene, and bromobenzene.

6. The process as claimed in claim 1, wherein said methyl haloformate is at least one selected from the group consisting of methyl chloroformate, methyl bromoformate, methyl iodoformate, and methyl fluoroformate.

7. The process as claimed in claim 1, wherein the molar ratio of said 3,4-dichloroaniline to said base is in the range of 1:1.1 to 1:1.5.

8. The process as claimed in claim 1, wherein the molar ratio of said 3,4-dichloroaniline to said methyl haloformate is in the range of 1:1.5 to 1:0.5.

9. The process as claimed in claim 1, wherein the molar ratio of said methyl N-(3,4-dichlorophenyl)carbamate to said dimethylamine is in the range of 1:1.1 to 1:1.5.
, Description:FIELD
The present disclosure relates to a process for the preparation of 3-(3,4-dichlorophenyl)-1,1-dimethylurea.
BACKGROUND
3-(3,4-dichlorophenyl)-1,1-dimethylurea is a phenylurea derivative and is used as an herbicidal agent.

3-(3,4-dichlorophenyl)-1,1-dimethylurea
Conventionally a process for the preparation of 3-(3,4-dichlorophenyl)-1,1-dimethylurea is known in the art, in which reaction of urea, dichloroaniline, and dimethylamine in ortho dichlorobenzene with the removal of ammonia provides 3-(3,4-dichlorophenyl)-1,1-dimethylurea. These reactants used in the aforestated process are expensive and need to be used in excess. Further, the reaction between urea and dichloroaniline results in large amount of impurities which are difficult to remove from the product mixture. The yield/productivity of 3-(3,4-dichlorophenyl)-1,1-dimethylurea, obtained from the known processes is considerably low.
There is, therefore, felt a need to provide a simple, efficient and economical process for the preparation of 3-(3,4-dichlorophenyl)-1,1-dimethylurea.

OBJECTS
Some of the objects of the present disclosure, which at least one embodiment herein satisfies, are as follows.
It is an object of the present disclosure to ameliorate one or more problems of the prior art or to at least provide a useful alternative.
An object of the present disclosure is to provide a simple and efficient process for preparing 3-(3,4-dichlorophenyl)-1,1-dimethylurea.
Another object of the present disclosure is to provide an economical process for preparing 3-(3,4-dichlorophenyl)-1,1-dimethylurea with comparatively high yield and high purity.
Other objects and advantages of the present disclosure will be more apparent from the following description, which is not intended to limit the scope of the present disclosure.
SUMMARY
The present disclosure relates to a process for preparing 3-(3,4-dichlorophenyl)-1,1-dimethylurea. The process comprises mixing 3,4-dichloroaniline, at least one first fluid media, and optionally at least one base to obtain a first mixture. The first mixture is reacted with methyl haloformate under stirring, at a temperature in the range of 15 °C to 60 °C to obtain a second mixture comprising methyl N-(3,4-dichlorophenyl)carbamate. The second mixture is allowed to settle to obtain a biphasic mixture comprising an organic layer and an aqueous layer. The aqueous layer is separated from the biphasic mixture to obtain the organic layer, followed by azeotropic dehydration of the organic layer to obtain an anhydrous organic layer comprising methyl N-(3,4-dichlorophenyl)carbamate. The methyl N-(3,4-dichlorophenyl)carbamate present in anhydrous organic layer is reacted with dimethyl amine at a temperature in the range of 120 °C to 140 °C with continuous removal of methanol to obtain a product mixture comprising 3-(3,4-dichlorophenyl)-1,1-dimethylurea. The product mixture is cooled at a temperature in the range of 10 °C to 25 °C to obtain a slurry. The so formed slurry is filtered to obtain a solid mass, followed by washing with at least one second fluid media, and drying the solid mass to obtain 3-(3,4-dichlorophenyl)-1,1-dimethylurea having purity greater than 98 %.
DETAILED DESCRIPTION
Different processes for the preparation of 3-(3,4-dichlorophenyl)-1,1-dimethylurea are known in the art. The reactants used to prepare 3-(3,4-dichlorophenyl)-1,1-dimethylurea are expensive and also the yield of the resultant 3-(3,4-dichlorophenyl)-1,1-dimethylurea, that is obtained from these known processes, is considerably low. Hence, the overall process, for the preparation of 3-(3,4-dichlorophenyl)-1,1-dimethylurea, is uneconomical.
The present disclosure envisages a process for the preparation of 3-(3,4-dichlorophenyl)-1,1-dimethylurea to mitigate the drawbacks mentioned herein above.
In accordance with the present disclosure, a process for the preparation of 3-(3,4-dichlorophenyl)-1,1-dimethylurea is provided. The process for the preparation of 3-(3,4-dichlorophenyl)-1,1-dimethylurea comprises the following steps.
In a first step, 3,4-dichloroaniline, at least one first fluid media, and optionally at least one base are mixed to obtain a first mixture.
In accordance with the embodiments of present disclosure, the base can be at least one selected from the group consisting of sodium bicarbonate, sodium hydroxide, sodium carbonate, potassium bicarbonate, potassium carbonate, potassium hydroxide, triethylamine, and trimethylamine. The base may be used to neutralize or remove any trapped acidity in the reaction mixture.
The molar ratio of 3,4-dichloroaniline to the base can be in the range of 1:1 to 1:1.5.
In accordance with one embodiment of the present disclosure, the molar ratio of 3,4-dichloroaniline to the base is 1:1.1.
The first fluid media is at least one selected from the group consisting of mono chlorobenzene, toluene, xylene, bromobenzene, ortho dichlorobenzene, and water.
In a second step, the first mixture is reacted with methyl haloformate under stirring, at a temperature in the range of 15 °C to 60 °C to obtain a second mixture comprising methyl N-(3,4-dichlorophenyl)carbamate.
The methyl haloformate can be at least one selected from the group consisting of methyl chloroformate, methyl bromoformate, methyl iodoformate, and methyl fluoroformate.
The molar ratio of 3,4-dichloroaniline to methyl haloformate can be in the range of 1:1.5 to 1:0.5.
In accordance with one embodiment of the present disclosure, the molar ratio of 3,4-dichloroaniline to methyl chloroformate is 1:1.2.
In a third step, the so formed second mixture is allowed to settle to obtain a biphasic mixture comprising an organic layer and an aqueous layer, followed by separating aqueous layer from the biphasic mixture to obtain the organic layer.
In accordance with one embodiment of the present disclosure, the methyl N-(3,4-dichlorophenyl)carbamate can be prepared by separating an aqueous layer from the biphasic mixture to obtain the organic layer, followed by washing with at least one base to remove any trapped acidity.
In the fourth step, the organic layer obtained in third step is azeotropically dehydrated to remove the moisture trapped in the organic layer and to obtain an anhydrous organic layer comprising methyl N-(3,4-dichlorophenyl)carbamate.
In accordance with one embodiment of the present disclosure, methyl N-(3,4-dichlorophenyl)carbamate can be separated from the organic layer.
In the fifth step, the methyl N-(3,4-dichlorophenyl)carbamate present in the anhydrous organic layer is reacted with dimethyl amine, at a temperature in the range of 120 °C to 140 °C with continuous removal of methanol to obtain a product mixture comprising 3-(3,4-dichlorophenyl)-1,1-dimethylurea.
The molar ratio of methyl N-(3,4-dichlorophenyl)carbamate to dimethylamine is in the range of 1:1.1 to 1:1.5.
In the sixth step, the product mixture is cooled at a temperature in the range of 10 °C to 25 °C to obtain a slurry.
In the seventh step, the slurry is filtered to obtain a solid mass, followed by washing with at least one second fluid media, and drying the solid mass to obtain 3-(3,4-dichlorophenyl)-1,1-dimethylurea having purity greater than 98 %.
The second fluid media is at least one selected from the group consisting of mono chlorobenzene, toluene, xylene, bromobenzene, and ortho dichlorobenzene.
The process of the present disclosure can be a one-pot reaction to prepare 3-(3,4-dichlorophenyl)-1,1-dimethylurea with high yield and high purity. The process is simple and efficient as the by-product such as methanol obtained by the process can be reused. Therefore, the process of the present disclosure to prepare 3-(3,4-dichlorophenyl)-1,1-dimethylurea is economical.
The present disclosure is further described in light of the following experiments which are set forth for illustration purpose only and not to be construed for limiting the scope of the disclosure. The following experiments can be scaled up to industrial/commercial scale and the results obtained can be extrapolated to industrial scale.
EXPERIMENT
Example 1: Process for preparation of 3-(3,4-dichlorophenyl)-1,1-dimethylurea in accordance with the process of the present disclosure.
Experiment 1:
300 ml of mono chlorobenzene and 250 ml of water were charged in a reactor with a central vertical stirrer, condenser and collection system to obtain a mixture. To this mixture, 162 g of 3,4-dichloroaniline were added to obtain a first mixture. The first mixture was stirred and reacted with 113.4 g of methyl chloroformate while controlling the temperature at 30 °C to obtain a second mixture containing methyl N-(3,4-dichlorophenyl)carbamate. Further, the second mixture was heated to 75 °C to obtain a biphasic mixture containing an organic layer and an aqueous layer. The aqueous layer was separated from the biphasic mixture to obtain the organic layer. The so formed organic layer was washed with 100 ml of 5 % sodium bicarbonate to remove any trap acidity, followed by azeotropic dehydration to remove trapped moisture to obtain methyl N-(3,4-dichlorophenyl)carbamate in organic phase. To this methyl N-(3,4-dichlorophenyl)carbamate, 56.25 g of dimethyl amine was passed at 130 °C with continuous removal of methanol to obtain a product mixture containing 3-(3,4-dichlorophenyl)-1,1-dimethylurea. The so formed product mixture was cooled to 20 °C to obtain a slurry. The slurry was filtered to obtain a product. The product was washed with 50 ml of mono chlorobenzene, followed by drying to obtain 3-(3,4-dichlorophenyl)-1,1-dimethylurea (yield = 92 %, HPLC purity= 99 %).

Experiment 2:
The process for the preparation of 3-(3,4-dichlorophenyl)-1,1-dimethylurea was similar to Experiment 1, except the organic solvent used in Experiment 2 was ortho dichlorobenzene (100 ml) instead of mono chlorobenzene. The yield of 3-(3,4-dichlorophenyl)-1,1-dimethylurea was 94 % and HPLC purity was 99.3 %.
Experiment 3:
The process for the preparation of 3-(3,4-dichlorophenyl)-1,1-dimethylurea was similar to Experiment 1, except the methyl haloformate used in Experiment 3 was methyl bromoformate (166.73 g) instead of methyl chloroformate. The results of Experiment 3 are found to be similar to Experiment 1.
The Experiment 1, Experiment 2, and Experiment 3 clearly indicate that the use of 3,4-dichloroaniline, methyl haloformate, and dimethylamine using afore-stated reaction process results in 3-(3,4-dichlorophenyl)-1,1-dimethylurea with high yields (> 90%) and high purity (= 99 %). The process also produces methanol as a by-product which can be reused. Also, it is a one-pot reaction and employs readily available reactants, hence the process for the preparation of 3-(3,4-dichlorophenyl)-1,1-dimethylurea is simple, efficient and economical.
Example 2: Process for the preparation of 3-(3,4-dichlorophenyl)-1,1-dimethylurea using two-step reaction.
Step I: Preparation and separation of methyl N-(3,4-dichlorophenyl)carbamate as an intermediate.
Experiment 4:
300 ml of mono chlorobenzene and 250 ml of water were charged into a reactor having central vertical stirrer, condenser and collection system to obtain a mixture. To this mixture, 162 g of 3,4-dichloroaniline and 100.8 g of sodium bicarbonate were added to obtain a first mixture. The first mixture was stirred and reacted with 113.4 g of methyl chloroformate while controlling the temperature at 30 °C to obtain a second mixture containing methyl N-(3,4-dichlorophenyl)carbamate. Further, the second mixture was heated to 75 °C to obtain a biphasic mixture containing an organic layer and an aqueous layer. The aqueous layer was separated from the biphasic mixture to obtain the organic layer, containing methyl N-(3,4-dichlorophenyl)carbamate. The so formed organic layer was cooled to 15 °C to obtain a slurry. The slurry was filtered to obtain a product. The product was washed with 50 ml of mono chlorobenzene, followed by drying to obtain methyl N-(3,4-dichlorophenyl)carbamate (yield = 90 %, HPLC purity= 100 %).
Experiment 5:
300 ml of mono chlorobenzene and 250 ml of water were charged into a reactor having central vertical stirrer, condenser and collection system to obtain a mixture. To this mixture, 162 g of 3,4-dichloroaniline and 100.8 g of sodium bicarbonate were added to obtain a first mixture. The first mixture was stirred and reacted with 113.4 g of methyl chloroformate while controlling the temperature at 30 °C to obtain a second mixture containing methyl N-(3,4-dichlorophenyl)carbamate. Further, the second mixture was heated to 75 °C to obtain a biphasic mixture containing an organic layer and an aqueous layer. The aqueous layer was separated from the biphasic mixture to obtain the organic layer, containing methyl N-(3,4-dichlorophenyl)carbamate. Further, mono chlorobenzene was evaporated to obtain methyl N-(3,4-dichlorophenyl)carbamate (yield = 99.5 %, HPLC purity= 99.8 %).
Experiment 6:
The process for the preparation of methyl N-(3,4-dichlorophenyl)carbamate was similar to Experiment 5, except the organic solvent and base used in Experiment 6 was ortho dichlorobenzene (300 ml) instead of mono chlorobenzene and 4 N sodium hydroxide solution (300 ml) instead of sodium bicarbonate respectively. The yield of methyl N-(3,4-dichlorophenyl)carbamate was 99 % and HPLC purity was 100 %.
Experiment 7:
500 ml of mono chlorobenzene and 162 g of 3,4-dichloroaniline were charged into a reactor having central vertical stirrer, condenser and collection system to obtain a mixture. The mixture was stirred and reacted with 113.4 g of methyl chloroformate while controlling the temperature at 30 °C to obtain a first mixture containing methyl N-(3,4-dichlorophenyl)carbamate. The first mixture was heated to 130 °C and maintained for 4 hours to obtain a clear solution and no more HCl evolution. Further, this first mixture was heated to 75 °C, followed by washing with 100 ml of 5 % sodium bicarbonate solution which removes any trapped acidity to obtain a biphasic mixture containing an organic layer and an aqueous layer. The aqueous layer was separated from the biphasic mixture to obtain the organic layer, containing methyl N-(3,4-dichlorophenyl)carbamate. Further, mono chlorobenzene was evaporated to obtain methyl N-(3,4-dichlorophenyl)carbamate (yield = 99 %, HPLC purity= 100 %).
Experiment 8:
300 ml of mono chlorobenzene and 250 ml of water were charged into a reactor having central vertical stirrer, condenser and collection system to obtain a mixture. To this mixture, 162 g of 3,4-dichloroaniline was added to obtain a first mixture. The first mixture was stirred and reacted with 166.73 g of methyl bromoformate while controlling the temperature at 40 °C to obtain a second mixture containing methyl N-(3,4-dichlorophenyl)carbamate. Further, the second mixture was heated to 75 °C to obtain a biphasic mixture containing an organic layer and an aqueous layer. The aqueous layer was separated from the biphasic mixture to obtain the organic layer, containing methyl N-(3,4-dichlorophenyl)carbamate, followed by washing with 100 ml of 5 % sodium bicarbonate solution to remove trapped acidity. Further, mono chlorobenzene was evaporated to obtain methyl N-(3,4-dichlorophenyl)carbamate (yield = 99.5 %, HPLC purity= 100 %).
The Experiments 4 to 8 clearly indicate that the use of methyl chloroformate and/or methyl bromoformate and 3,4-dichloroaniline using the afore-stated reaction process results in methyl N-(3,4-dichlorophenyl)carbamate, which is separated as an intermediate, with high yield and high purity.
Step II: Process for the preparation of 3-(3,4-dichlorophenyl)-1,1-dimethylurea from methyl N-(3,4-dichlorophenyl)carbamate obtained from Experiments 4 to 8.
Experiment 9:
300 ml of mono chlorobenzene and 220 g of methyl N-(3,4-dichlorophenyl)carbamate were charged in a reactor with central vertical stirrer, condenser and collection system to obtain a mixture. The so formed mixture was stirred and heated to 130 °C. To this mixture, 56.25 g of dimethylamine was passed with continuous removal of methanol to obtain a product mixture containing 3-(3,4-dichlorophenyl)-1,1-dimethylurea. The so formed product mixture was cooled to 20 °C to obtain a slurry. The slurry was filtered to obtain a product. The product was washed with 50 ml of mono chlorobenzene, followed by drying to obtain 3-(3,4-dichlorophenyl)-1,1-dimethylurea (yield = 91 %, HPLC purity= 99.2 %).
Experiment 10:
300 ml of mono chlorobenzene and 220 g of methyl N-(3,4-dichlorophenyl)carbamate were charged in a reactor with central vertical stirrer, condenser and collection system to obtain a mixture. The so formed mixture was stirred and heated to 130 °C. To this mixture, 56.25 g of dimethylamine was passed with continuous removal of methanol by controlling pressure at 0.8 kg/cm2 to obtain a product mixture containing 3-(3,4-dichlorophenyl)-1,1-dimethylurea. The so formed product mixture was cooled to 20 °C to obtain a slurry. The slurry was filtered to obtain a product. The product was washed with 50 ml of mono chlorobenzene, followed by drying to obtain 3-(3,4-dichlorophenyl)-1,1-dimethylurea (yield = 80 %, HPLC purity= 99.5 %).
The Experiment 9 and Experiment 10 clearly indicate that the use of methyl N-(3,4-dichlorophenyl)carbamate and diethylamine using afore-stated reaction process results in 3-(3,4-dichlorophenyl)-1,1-dimethylurea with high yields (> 80 %) and high purity (> 99 %). The process to prepare 3-(3,4-dichlorophenyl)-1,1-dimethylurea also produces methanol as a by-product which can be reused. However, the yield of 3-(3,4-dichlorophenyl)-1,1-dimethylurea obtained by using Experiment 10 is comparably low as reaction is carried out at controlled pressure, compared to the yield of 3-(3,4-dichlorophenyl)-1,1-dimethylurea obtained by using Experiment 9. Overall, the process to prepare 3-(3,4-dichlorophenyl)-1,1-dimethylurea is simple, efficient and economical.
TECHNICAL ADVANCES AND ECONOMICAL SIGNIFICANCE
The present disclosure, described herein above has several technical advantages including, but not limited to, the realization of a process for the preparation of 3-(3,4-dichlorophenyl)-1,1-dimethylurea, wherein the process:
- is simple and efficient;
- is economical; and
- provides comparatively high yield and high purity of 3-(3,4-dichlorophenyl)-1,1-dimethylurea.
Throughout this specification the word “comprise”, or variations such as “comprises” or “comprising”, will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.
The use of the expression “at least” or “at least one” suggests the use of one or more elements or ingredients or quantities, as the use may be in the embodiment of the disclosure to achieve one or more of the desired objects or results.
Any discussion of documents, acts, materials, devices, articles or the like that has been included in this specification is solely for the purpose of providing a context for the disclosure. It is not to be taken as an admission that any or all of these matters form a part of the prior art base or were common general knowledge in the field relevant to the disclosure as it existed anywhere before the priority date of this application.
The numerical values mentioned for the various physical parameters, dimensions or quantities are only approximations and it is envisaged that the values higher/lower than the numerical values assigned to the parameters, dimensions or quantities fall within the scope of the disclosure, unless there is a statement in the specification specific to the contrary.
While considerable emphasis has been placed herein on the components and component parts of the preferred embodiments, it will be appreciated that many embodiments can be made and that many changes can be made in the preferred embodiments without departing from the principles of the disclosure. These and other changes in the preferred embodiment as well as other embodiments of the disclosure will be apparent to those skilled in the art from the disclosure herein, whereby it is to be distinctly understood that the foregoing descriptive matter is to be interpreted merely as illustrative of the disclosure and not as a limitation.