DESC:FIELD
The present disclosure relates to a process for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile.
BACKGROUND
The background information herein below relates to the present disclosure but is not necessarily prior art.
4-Chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile is used as a key intermediate for the synthesis of Cyazofamid. The structure of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile is:

Cyazofamid is an important fungicide. The chemical name of Cyazofamid is 4-chloro-2-cyano-N,N-dimethyl-5-(4-methylphenyl)-1H-imidazole-1-sulfonamide. The structure of Cyazofamid is:

Conventionally, the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile is carried out in DMF in the presence of sodium bisulfite followed by chlorination by using N-chlorosuccinimide (NCS). N-Chlorosuccinimide (NCS) is expensive and also succinimide by-products formed during the reaction requires tedious work up to remove such by-products.
Moreover, the conventional methods for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile are associated with drawbacks such as harsh reaction conditions, long reaction time, low yields and use of toxic, expensive, or less readily available reagents, are not feasible and have handling limitations during synthesis. Thus, the conventional methods do not provide an efficient solution for the synthesis of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile.
Therefore, there is felt a need to provide a process for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile that mitigates the aforestated drawbacks or at least provides a useful alternative.
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 background or to at least provide a useful alternative.
Another object of the present disclosure is to provide a process for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile.
Yet another object of the present disclosure is to provide a process for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile with a comparatively better purity and better yield.
Still another object of the present disclosure is to provide a simple, efficient and cost-effective process for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile.
Yet another object of the present disclosure is to provide an environment friendly and commercially scalable process for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile.
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 the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile. The process for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile comprises reacting a compound of Formula II with a chlorinating agent in a fluid medium followed by reacting with a reducing agent, optionally, in presence of an organic base.
In a first embodiment of the present disclosure, the process for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile comprises the following steps:
a. reacting a compound of Formula II with a chlorinating agent in a fluid medium under stirring at a first predetermined temperature for a first predetermined time period to obtain a mixture of compounds of Formula III and Formula I;

b. reducing the mixture of compounds of Formula III and Formula I in fluid medium by using a reducing agent under stirring at a second predetermined temperature for a second predetermined time period to obtain 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile (Formula I).

In a second embodiment of the present disclosure, the process for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile comprises reacting a compound of Formula II with a chlorinating agent in a fluid medium under stirring at a first predetermined temperature for a first predetermined time period to obtain a reaction mixture followed by adjusting pH of the reaction mixture by using a base and then adding a reducing agent and stirring at a second predetermined temperature for a second predetermined time period to obtain 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile (Formula I).

In an embodiment of the present disclosure, the chlorinating agent is thionyl chloride.
In an embodiment of the present disclosure, the molar ratio of the compound of Formula II to the chlorinating agent is in the range of 1:1.5 to 1:5.
In an embodiment of the present disclosure, the fluid medium is selected from the group consisting of dimethylformamide (DMF), dimethyl acetamide, sulfolane, dimethyl sulfoxide, N-methylpyrrolidine, acetonitrile, benzonitrile and combination thereof.
In an embodiment of the present disclosure, the first predetermined temperature is in the range of 0 °C to 60 °C.
In an embodiment of the present disclosure, the first predetermined time period is in the range of 2 hours to 10 hours.
In a second embodiment of the present disclosure, the base is selected from an organic base and an inorganic base.
The organic base is selected from the group consisting of triethylamine, diisopropylammonia, pyridine, piperidine and morpholine.
The inorganic base is selected from the group consisting of ammonia, potassium carbonate, sodium carbonate, potassium hydroxide and sodium hydroxide.
In an embodiment of the present disclosure, the reducing agent is selected from the group consisting of metal salts of sulfur-containing derivatives, sodium metabisulfite, sodium bisulfite, sodium sulfite, potassium bisulfite, potassium metabisulfite, potassium sulfite, potassium dithionite, sodium dithionite and a combination thereof.
In an embodiment of the present disclosure, the molar ratio of the compound of Formula II to the reducing agent is in the range of 1:0.1 to 1:1.
In an embodiment of the present disclosure, the molar ratio of the compound of Formula II to the base is in the range of 1:1 to 1:3.
In an embodiment of the present disclosure, the second predetermined temperature is in the range of 40 °C to 150 °C.
In an embodiment of the present disclosure, the second predetermined time period is in the range of 1 hour to 15 hours.
In an embodiment of the present disclosure, the yield of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile is in the range of 60% to 80% and a purity is in the range of 90% to 96%.
DETAILED DESCRIPTION
The present disclosure relates to a process for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile.
Embodiments, of the present disclosure, will now be described herein. Embodiments are provided so as to thoroughly and fully convey the scope of the present disclosure to the person skilled in the art. Numerous details are set forth, relating to specific components, and methods, to provide a complete understanding of embodiments of the present disclosure. It will be apparent to the person skilled in the art that the details provided in the embodiments should not be construed to limit the scope of the present disclosure. In some embodiments, well-known processes, well-known apparatus structures, and well-known techniques are not described in detail.
The terminology used, in the present disclosure, is only for the purpose of explaining a particular embodiment and such terminology shall not be considered to limit the scope of the present disclosure. As used in the present disclosure, the forms "a,” "an," and "the" may be intended to include the plural forms as well, unless the context clearly suggests otherwise. The terms "comprises," "comprising," “including,” and “having,” are open ended transitional phrases and therefore specify the presence of stated features, integers, steps, operations, elements, modules, units and/or components, but do not forbid the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof. The particular order of steps disclosed in the method and process of the present disclosure is not to be construed as necessarily requiring their performance as described or illustrated. It is also to be understood that additional or alternative steps may be employed.
As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed elements.
The terms first, second, third, etc., should not be construed to limit the scope of the present disclosure as the aforementioned terms may be only used to distinguish one element, component, region, layer or section from another component, region, layer or section. Terms such as first, second, third etc., when used herein do not imply a specific sequence or order unless clearly suggested by the present disclosure.
Conventionally, the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile is carried out in DMF in the presence of sodium bisulfite followed by chlorination by using N-chlorosuccinimide (NCS). N-Chlorosuccinimide (NCS) is expensive and also succinimide by-products formed during the reaction requires tedious work up to remove such by-products.
Moreover, the conventional methods for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile are associated with drawbacks such as harsh reaction conditions, long reaction time, low yields and use of toxic, expensive, or less readily available reagents, are not feasible and have handling limitations during synthesis. Thus, the conventional methods do not provide an efficient solution for the synthesis of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile.
The present disclosure provides an improved process for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile. The structure of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile is represented as Formula I:

The process of the present disclosure is simple, efficient, environment friendly, economical, and results in improved yield and higher purity of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile.
In accordance with the present disclosure, the process for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile (Formula I) comprises reacting the compound of Formula II with a chlorinating agent in a fluid medium followed by reacting with a reducing agent, optionally, in presence of an organic base.
In a first embodiment, the present disclosure provides a two-step process for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile (Formula I).
In a second embodiment, the present disclosure provides a single step process for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile (Formula I).
In accordance with the first embodiment of the present disclosure, the process for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile (Formula I), comprising the following steps:
a) reacting a compound of Formula II with a chlorinating agent in a fluid medium under stirring at a first predetermined temperature for a first predetermined time period to obtain a mixture of compounds of Formula III and Formula I; and

b) reducing the mixture of the compounds of Formula III and Formula I in the fluid medium by using a reducing agent under stirring at a second predetermined temperature for a second predetermined time period to obtain 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile (Formula I).

In accordance with the first embodiment of the present disclosure, the chlorinating agent is thionyl chloride.
In accordance with the first embodiment of the present disclosure, the molar ratio of the compound of formula II to the chlorinating agent is in the range of 1:1.5 to 1:5. In an exemplary embodiment of the present disclosure, the molar ratio of the compound of formula II to the chlorinating agent is 1:2.5.
In accordance with the first embodiment of the present disclosure, the fluid medium is selected from the group consisting of dimethylformamide (DMF), dimethyl acetamide, sulfolane, dimethyl sulfoxide, N-methylpyrrolidine, acetonitrile, benzonitrile and combination thereof. In an exemplary embodiment of the present disclosure, the fluid medium is selected from the group consisting of dimethylformamide (DMF).
In accordance with the first embodiment of the present disclosure, the first predetermined temperature is in the range of 0 °C to 60 °C. In an exemplary embodiment of the present disclosure, the first predetermined temperature is 30 °C.
In accordance with the first embodiment of the present disclosure, the first predetermined time period is in the range of 2 hours to 10 hours. In an exemplary embodiment of the present disclosure, the first predetermined time period is 4 hours.
In accordance with the first embodiment of the present disclosure, the reducing agent is selected from the group consisting of metal salts of sulfur-containing derivatives, sodium metabisulfite, sodium bisulfite, sodium sulfite, potassium bisulfite, potassium metabisulfite, potassium sulfite, potassium dithionite, sodium dithionite and a combination thereof. In an exemplary embodiment of the present disclosure, the reducing agent is sodium metabisulfite.
In accordance with the first embodiment of the present disclosure, the second predetermined temperature is in the range of 40 °C to 150 °C. In a preferred embodiment of the present disclosure, the second predetermined temperature is 80 °C to 100 °C. In an exemplary embodiment of the present disclosure, the second predetermined temperature is 90 °C.
In accordance with the first embodiment of the present disclosure, the second predetermined time period is in the range of 1 hour to 15 hours. In a preferred embodiment of the present disclosure, the second predetermined time period is 4 hours to 8 hours. In an exemplary embodiment of the present disclosure, the second predetermined time period is 6 hours.
In accordance with the first embodiment of the present disclosure, the yield of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile is in the range of 60% to 80% and a purity is in the range of 90% to 96%. In an exemplary embodiment of the present disclosure the yield of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile is 64.29% and the purity is 94%.
In accordance with the second embodiment of the present disclosure, the process for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile (Formula I) comprises reacting a compound of Formula II with a chlorinating agent in a fluid medium under stirring at a first predetermined temperature for a first predetermined time period to obtain a reaction mixture followed by adjusting pH of the reaction mixture by using a base and then adding a reducing agent and stirring at a second predetermined temperature for a second predetermined time period to obtain 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile (Formula I).

In accordance with the second embodiment of the present disclosure, the chlorinating agent is thionyl chloride.
In accordance with an embodiment of the present disclosure, multiple reactions take place during the conversion of the compound of Formula II to the compound of Formula I viz. de-protection, dehydration, reduction and chlorination by using the chlorinating agent. Particularly, the use of thionyl chloride in the process leads to these multiple reactions such as de-protection, dehydration, reduction and chlorination to take place in a single step thereby making the process efficient and economic.
The process of the present disclosure avoids using multiple reagents for carrying out multiple reactions.
In accordance with the second embodiment of the present disclosure, the molar ratio of the compound of formula II to the chlorinating agent is in the range of 1:1.5 to 1:5. In an exemplary embodiment of the present disclosure, the molar ratio of the compound of formula II to the chlorinating agent is 1:2.5.
In accordance with the second embodiment of the present disclosure, the fluid medium is selected from the group consisting of dimethylformamide (DMF), dimethyl acetamide, sulfolane, dimethyl sulfoxide, N-methylpyrrolidine, acetonitrile, benzonitrile and combination thereof. In an exemplary embodiment of the present disclosure, the fluid medium is selected from the group consisting of dimethylformamide (DMF).
In accordance with the second embodiment of the present disclosure, the first predetermined temperature is in the range of 0 °C to 60 °C. In an exemplary embodiment of the present disclosure, the first predetermined temperature is 30 °C.
In accordance with the second embodiment of the present disclosure, the first predetermined time period is in the range of 2 hours to 10 hours. In an exemplary embodiment of the present disclosure, the first predetermined time period is 4 hours.
In accordance with the second embodiment of the present disclosure, the base is selected from an organic base and an inorganic base.
The organic base is selected from the group consisting of triethylamine, diisopropylammonia, pyridine, piperidine and morpholine. In an exemplary embodiment of the present disclosure, an organic base is triethylamine.
The inorganic base is selected from the group consisting of ammonia, potassium carbonate, sodium carbonate, potassium hydroxide and sodium hydroxide.
In accordance with the second embodiment of the present disclosure, the reducing agent is selected from the group consisting of metal salts of sulfur-containing derivatives, sodium metabisulfite, sodium bisulfite, sodium sulfite, potassium bisulfite, potassium metabisulfite, potassium sulfite, potassium dithionite, sodium dithionite and a combination thereof. In an exemplary embodiment of the present disclosure, the reducing agent is sodium metabisulfite.
In accordance with the second embodiment of the present disclosure, the molar ratio of the compound of formula II to the reducing agent is in the range of 1:0.1 to 1:1. In an exemplary embodiment of the present disclosure, the molar ratio of the compound of formula II to the reducing agent is 1:0.33.
In accordance with the second embodiment of the present disclosure, the molar ratio of the compound of formula II to the base is in the range of 1:1 to 1:3. In an exemplary embodiment of the present disclosure, the molar ratio of the compound of formula II to the base is in the range of 1:1.33.
In accordance with the second embodiment of the present disclosure, the second predetermined temperature is in the range of 40 °C to 150 °C. In an exemplary embodiment of the present disclosure, the second predetermined temperature is 50°C.
In accordance with the second embodiment of the present disclosure, the second predetermined time period is in the range of 1 hour to 15 hours. In an exemplary embodiment of the present disclosure, the second predetermined time period is 2 hours.
In accordance with the second embodiment of the present disclosure, the yield of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile is in the range of 60% to 80% and a purity is in the range of 90% to 96%. In an exemplary embodiment of the present disclosure the yield of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile is 77.15 % and the purity is 93%. In another exemplary embodiment of the present disclosure the yield of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile is 64.29 % and the purity is 94%.
The present disclosure provides a simple, environment friendly and economic process for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile with a comparatively better yield and better purity.
The foregoing description of the embodiments has been provided for purposes of illustration and is not intended to limit the scope of the present disclosure. Individual components of a particular embodiment are generally not limited to that particular embodiment, but, are interchangeable. Such variations are not to be regarded as a departure from the present disclosure, and all such modifications are considered to be within the scope of the present disclosure.
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 the industrial scale.
EXPERIMENTAL DETAILS
EXAMPLE 1: A two-step process for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile (Formula I) in accordance with the present disclosure
Step (a) - Synthesis of a mixture of compounds of Formula-III and Formula-I:
2 litre 4-necked round bottom flask (RBF) was equipped with a condenser, thermometer pocket, a dropping funnel, and an agitator. RBF was charged with 200 g of l-hydroxy-4-(4-methylphenyl)-3-oxide-1H-imidazole-2-carboxaldehyde oxime (Formula-II) and 600 ml dimethylformamide (DMF) under stirring at 30 °C to obtain a first mixture. To this mixture, 250 g of thionyl chloride was added under stirring at 30 °C and after completion of thionyl chloride addition, the mixture was stirred at 30 °C for 4 hours to obtain a first product mixture.
To the first product mixture, 50 ml water was added and the resultant product mixture was added slowly into 2 litre water and stirred for 2 hours to obtain solids. The obtained solid was filtered and washed with 200 ml water and dried to obtain 180 g of a mixture of compounds of Formula III and Formula I in 50:50 ratio (mixture purity 83%).
Step (b) - Synthesis of the compound of Formula-I:
2 litre 4-necked RBF was equipped with a condenser, thermometer pocket, a dropping funnel, and an agitator. RBF was charged with 170 g of the mixture of the compounds of Formula III and Formula I and 500 ml of DMF under stirring at 30 °C to obtain a second mixture. The second mixture was heated at 90 °C under stirring followed by adding 80 g of sodium metabisulfite under stirring at 90 °C and the stirring was continued at 90 °C for 6 hours to obtain a second product mixture.
To the second product mixture, 50 ml water was added to make a homogeneous mass. The resulting homogeneous mass was dropped slowly into 2 litre water and stirred for 2 hours to obtain solids. The obtained solid was filtered and washed with 200 ml water and purified from aqueous acetone and dried to get 120 g of compound of Formula-I (purity 94% and yield 64.29%).
EXAMPLE 2: A single step process for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile (Formula I) in accordance with the present disclosure
250 mL 4-necked RBF was equipped with a condenser, thermometer pocket, a dropping funnel, and an agitator. RBF was charged with 25 g of l-hydroxy-4-(4-methylphenyl)-3-oxide-1H-imidazole-2-carboxaldehyde oxime (Formula-II) and 75 ml of DMF under stirring at 30 °C to obtain a mixture. To this mixture, thionyl chloride was added under stirring at 30 °C and after completion of thionyl chloride addition, the mixture was stirred at 30 °C for 4 hours to obtain a reaction mixture. The pH of the reaction mixture was adjusted to neutral by adding 20 ml of triethyl amine and then 7 g of sodium metabisulfite was added at 30 °C under stirring and the resulting mass was heated to 50 °C for 2 hours under stirring to obtain a product mixture.
To the product mixture, 20 ml water was added and the resulting product mixture was added slowly into 250 ml water and stirred for 2 hours to obtain solids. The obtained solid was filtered and washed with 20 ml water and purified from aqueous acetone and dried to get 18 g of compound of Formula-I (purity 93% and yield 77.15%).
COMPARATIVE EXAMPLES:
Comaparative Example 1 (Conventional process for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile):
In a first step, l-hydroxy-4-(4-methylphenyl)-3-oxide-1H-imidazole-2-carboxaldehyde oxime (0.95 mole) and 750 ml ?,?-dimethylacetamide were mixed in 5 litre flask and heated to 100°C. Sodium metabisulfite (235g, 1.2 moles) was charged in portions to obtain a mixture. The mixture was maintained at 100°C for 8 hours to obtain reaction mixture. The mixture was cooled to a room temperature and 2000ml of water was added to precipitate the product. The solid was filtered off and washed with water and toluene, and washed solids were dried. 139 g of crude(4-methylphenyl)- lH-imidazole-2-carbonitrile was obtained, purity 94.6%.
In a second step, 110 g of the product from first step was mixed in 500 ml flask with 55 ml N,N- dimethylacetamide and 55 ml acetonitrile. 86 g of N-chlorosuccinimide (NCS) was added, maintaining the temperature below 25°C. After the addition was complete the mixture was stirred for 1 hour at 20°C. The reaction mass was neutralized with 10% sodium hydroxide, and stirred for 1 hour to obtain a crude product mixture. The crude product was filtered off, washed with water, re-slurried in toluene, filtered, and dried in a vacuum oven to obtain 104 g of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile.
The schematic representation for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile in accordance with the comparative example 2 is illustrated below as scheme III:

From the example 1 and the comparative examples 1, it is observed that process for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile in accordance with the present disclosure is a single pot process with minimum reagents (catalytic amount only) and the final product 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile obtained is with comparatively better yield and better purity.
Further, the reaction conditions in the process of the present disclosure are milder as compared to the process of the comparative example. In addition, in the comparative example, the chlorination is carried out by using N-chlorosuccinimide (NCS). NCS is expensive and also leads to the formation of succinimide by-products during the reaction. The removal of such by-products is problematic as it requires tedious work up.
Furthermore, in the process of the present disclosure, multiple reactions such as de-protection, dehydration, reduction and chlorination take place in a single step by using only one reagent i.e. thionyl chloride making the process efficient, economic and environment friendly.
TECHNICAL ADVANCEMENT
The present disclosure described hereinabove has several technical advantages including, but not limited to, the realization of a process for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile that;
• employs non-hazardous, inexpensive and readily available raw material/reagents;
• requires comparatively shorter reaction time;
• generates comparatively less impurities;
• is commercially scalable;
• is simple, efficient, cost effective and environment friendly; and
• provides 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile with a comparatively better purity and better yield.
The embodiments herein and the various features and advantageous details thereof are explained with reference to the non-limiting embodiments in the following description. Descriptions of well-known components and processing techniques are omitted so as to not unnecessarily obscure the embodiments herein. The examples used herein are intended merely to facilitate an understanding of ways in which the embodiments herein may be practiced and to further enable those of skill in the art to practice the embodiments herein. Accordingly, the examples should not be construed as limiting the scope of the embodiments herein.
The foregoing description of the specific embodiments so fully reveal the general nature of the embodiments herein that others can, by applying current knowledge, readily modify and/or adapt for various applications such specific embodiments without departing from the generic concept, and, therefore, such adaptations and modifications should and are intended to be comprehended within the meaning and range of equivalents of the disclosed embodiments. It is to be understood that the phraseology or terminology employed herein is for the purpose of description and not of limitation. Therefore, while the embodiments herein have been described in terms of preferred embodiments, those skilled in the art will recognize that the embodiments herein can be practiced with modification within the spirit and scope of the embodiments as described herein.
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 invention to achieve one or more of the desired objects or results. While certain embodiments of the inventions have been described, these embodiments have been presented by way of example only, and are not intended to limit the scope of the inventions. Variations or modifications to the formulation of this invention, within the scope of the invention, may occur to those skilled in the art upon reviewing the disclosure herein. Such variations or modifications are well within the spirit of this invention.
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 given for various physical parameters, dimensions, and quantities are only approximate values and it is envisaged that the values higher than the numerical value assigned to the physical parameters, dimensions, and quantities fall within the scope of the invention unless there is a statement in the specification to the contrary.
While considerable emphasis has been placed herein on the specific features of the preferred embodiment, it will be appreciated that many additional features can be added and that many changes can be made in the preferred embodiment without departing from the principles of the disclosure. These and other changes in the preferred embodiment 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. ,CLAIMS:WE CLAIM:
1. A process for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile (Formula I), said process comprises reacting a compound of Formula II with a chlorinating agent in a fluid medium followed by reacting with a reducing agent, optionally, in presence of an organic base.
2. The process as claimed in claim 1 comprising the following steps:
a) reacting a compound of Formula II with a chlorinating agent in a fluid medium under stirring at a first predetermined temperature for a first predetermined time period to obtain a mixture of compounds of Formula III and Formula I; and

b) reducing said mixture of the compounds of Formula III and Formula I in the fluid medium by using a reducing agent under stirring at a second predetermined temperature for a second predetermined time period to obtain 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile (Formula I).

3. The process as claimed in claim 1 comprises reacting a compound of Formula II with a chlorinating agent in a fluid medium under stirring at a first predetermined temperature for a first predetermined time period to obtain a reaction mixture followed by adjusting pH of the reaction mixture by using a base and then adding a reducing agent and stirring at a second predetermined temperature for a second predetermined time period to obtain 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile (Formula I).

4. The process as claimed in claim 2 and 3, wherein said chlorinating agent is thionyl chloride.
5. The process as claimed in claim 2 and 3, wherein said a molar ratio of said compound of formula II to said chlorinating agent is in the range of 1:1.5 to 1:5.
6. The process as claimed in claim 2 and 3, wherein said fluid medium is selected from the group consisting of dimethylformamide (DMF), dimethyl acetamide, sulfolane, dimethyl sulfoxide, N-methylpyrrolidine, acetonitrile, benzonitrile and combination thereof.
7. The process as claimed in claim 2 and 3, wherein said first predetermined temperature is in the range of 0 °C to 60 °C.
8. The process as claimed in claim 2 and 3, wherein said first predetermined time period is in the range of 2 hours to 10 hours.
9. The process as claimed in claim 3, wherein said base is selected from an organic base and an inorganic base.
10. The process as claimed in claim 9, wherein
• said organic base is selected from the group consisting of triethylamine, diisopropylammonia, pyridine, piperidine and morpholine; and
• said inorganic base is selected from the group consisting of ammonia, potassium carbonate, sodium carbonate, potassium hydroxide and sodium hydroxide.
11. The process as claimed in claim 2, wherein said reducing agent is selected from the group consisting of metal salts of sulfur-containing derivatives, sodium metabisulfite, sodium bisulfite, sodium sulfite, potassium bisulfite, potassium metabisulfite, potassium sulfite, potassium dithionite, sodium dithionite and a combination thereof.
12. The process as claimed in claim 3, wherein said a molar ratio of said compound of formula II to said reducing agent is in the range of 1:0.1 to 1:1.
13. The process as claimed in claim 3, wherein said a molar ratio of said compound of formula II to said base is in the range of 1:1 to 1:3.
14. The process as claimed in claim 2, wherein said second predetermined temperature is in the range of 40 °C to 150 °C.
15. The process as claimed in claim 2, wherein said second predetermined time period is in the range of 1 hour to 15 hours.
16. The process as claimed in claim 1, wherein a yield of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile is in the range of 60% to 80% and a purity is in the range of 90% to 96%.
Dated this 07th day of March, 2024

_______________________________
MOHAN RAJKUMAR DEWAN, IN/PA – 25
of R.K.DEWAN & CO.
Authorized Agent of Applicant

TO,
THE CONTROLLER OF PATENTS
THE PATENT OFFICE, AT CHENNAI