METHOD FOR THE PREPARATION OF 4-CHLORO-5-(4-METHYLPHENYL)-1H-IMIDAZOLE-2-CARBONITRILE

Abstract

The present invention relates to a process for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile. The process of the present invention is carried out under mild reaction conditions. Furthermore, the process of the present invention is simple, cost-effective, and environmentally friendly, and provides 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile with comparatively higher purity and better yield.

Description

TECHNICAL AREA

[0001] The present invention relates to a process for the production of 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile. STATE OF THE ART

[0002] The following background information relates to the present invention, but does not necessarily represent prior art.

[0003] 4-Chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile serves as a key intermediate in the synthesis of cyazofamide. The structure of 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile is as follows:

[0004] Cyazofamide is an important fungicide. Its chemical name is 4-chloro-2-cyano-N,N-dimethyl-5-(4-methylphenyl)-1H-imidazol-1-sulfonamide. The structure of cyazofamide is as follows:

[0005] The synthesis of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile is usually carried out in DMF in the presence of sodium bisulfite, followed by chlorination with N-chlorosuccinimide (NCS). N-chlorosuccinimide (NCS) is expensive, and the removal of the succinimide byproducts formed during the reaction is also labor-intensive.

[0006] Furthermore, conventional methods for the synthesis of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile are associated with disadvantages such as harsh reaction conditions, long reaction times, low yields, and the use of toxic, expensive, or difficult-to-obtain reagents, rendering them impractical and subject to handling restrictions during synthesis. Therefore, conventional methods do not offer an efficient solution for the synthesis of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile.

[0007] Therefore, there is a need to provide a method for the production of 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile that reduces the aforementioned disadvantages or at least offers a useful alternative. TASK OF INVENTION

[0008] Some of the problems of the present invention, which are fulfilled by at least one embodiment described herein, are as follows: One object of the present invention is to solve one or more problems of the prior art or at least to provide a useful alternative. Another object of the present invention is to provide a process for the production of 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile. Another object of the present invention is to provide a process for the production of 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile with comparatively better purity and better yield. Another object of the present invention is to provide a simple, efficient and cost-effective process for the production of 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile. Another object of the present invention is to provide an environmentally friendly and commercially scalable process for the production of 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile.

[0009] Further tasks and advantages of the present invention will become more apparent from the following description, which is not intended to limit the scope of protection of the present invention. BRIEF DESCRIPTION OF THE INVENTION

[0010] The present invention relates to a process for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile. The process for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile comprises the reaction of a compound of formula II with a chlorinating agent in a liquid medium, and subsequently the reaction with a reducing agent, optionally in the presence of an organic base.

[0011] In a first embodiment of the present invention, the process for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile comprises the following steps: a. Reacting a compound of formula II with a chlorinating agent in a liquid medium while stirring at a first predetermined temperature for a first predetermined period of time, in order to obtain a mixture of compounds of formula III and formula I; b. Reducing the mixtures of compounds of formula III and formula I in a liquid medium using a reducing agent under stirring at a second predetermined temperature for a second predetermined period to obtain 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile (formula I).

[0012] In a second embodiment of the present invention, the process for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile comprises reacting a compound of formula II with a chlorinating agent in a liquid medium with stirring at a first predetermined temperature for a first predetermined period to obtain a reaction mixture, followed by adjusting the pH of the reaction mixture using a base and subsequently adding a reducing agent and stirring at a second predetermined temperature for a second predetermined period to obtain 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile (formula I).

[0013] In one embodiment of the present invention, the chlorinating agent is thionyl chloride.

[0014] In one embodiment of the present invention, the molar ratio of the compound of formula II to the chlorinating agent is in the range of 1:1.5 to 1:5.

[0015] In one embodiment of the present invention, the liquid medium is selected from the group consisting of dimethylformamide (DMF), dimethylacetamide, sulfolane, dimethyl sulfoxide, N-methylpyrrolidine, acetonitrile, benzonitrile and combinations thereof.

[0016] In one embodiment of the present invention, the first predetermined temperature is in the range of 0 °C to 60 °C.

[0017] In one embodiment of the present invention, the first predetermined period is in the range of 2 hours to 10 hours.

[0018] In a second embodiment of the present invention, the base is selected from an organic base and an inorganic base.

[0019] The organic base is selected from the group consisting of triethylamine, diisopropylamine, pyridine, piperidine and morpholine.

[0020] The inorganic base is selected from the group consisting of ammonia, potassium carbonate, sodium carbonate, potassium hydroxide and sodium hydroxide.

[0021] In one embodiment of the present invention, 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 combinations thereof.

[0022] In one embodiment of the present invention, the molar ratio of the compound of formula II to the reducing agent is in the range of 1:0.1 to 1:1.

[0023] In one embodiment of the present invention, the molar ratio of the compound of formula II to the base is in the range of 1:1 to 1:3.

[0024] In one embodiment of the present invention, the second predetermined temperature is in the range of 40 °C to 150 °C.

[0025] In one embodiment of the present invention, the second predetermined period is in the range of 1 hour to 15 hours.

[0026] In one embodiment of the present invention, the yield of 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile is in the range of 60% to 80%.

[0027] 4-Chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile is prepared according to the process of the present invention.

[0028] In one embodiment of the present invention, the 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile has a purity of more than 90%.

[0029] In one embodiment of the present invention, the purity of 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile is in the range of 90% to 96%. DETAILED DESCRIPTION

[0030] The present invention relates to a process for the production of 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile.

[0031] Embodiments of the present invention are described below. These embodiments are provided to fully and completely convey the scope of protection of the present invention to those skilled in the art. Numerous details of specific components and methods are given to enable a complete understanding of the embodiments of the present invention. It will be clear to those skilled in the art that the details provided in the embodiments are not to be understood as limiting the scope of protection of the present invention. In certain embodiments, known methods, known apparatus structures, and known techniques are not described in detail.

[0032] The terminology used in the present invention serves solely to explain a particular embodiment and is not to be understood as limiting the scope of protection of the present invention. As used in the present invention, the forms "a", "an", and "the" may also include the plural forms unless otherwise indicated by the context. The terms "comprises", "comprising", "including", and "having" are open transitional formulations and therefore denote the presence of the aforementioned features, integers, steps, processes, elements, modules, units, and / or components, but do not preclude the presence or addition of one or more further features, integers, steps, processes, elements, components, and / or groups thereof.The specific sequence of steps disclosed in the method and process of the present invention is not to be understood as requiring them to be carried out in the manner described or illustrated. It is also to be understood that additional or alternative steps may be used.

[0033] As used herein, the term “and / or” includes any and all combinations of one or more of the related listed elements.

[0034] The terms first, second, third, etc., are not to be understood as limiting the scope of protection of the present invention, since these terms merely serve to distinguish one element, component, region, layer, or section from another. Terms such as first, second, third, etc., as used herein, do not imply any particular order or sequence unless clearly suggested by the present invention.

[0035] The synthesis of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile is usually carried out in DMF in the presence of sodium bisulfite, followed by chlorination with N-chlorosuccinimide (NCS). N-chlorosuccinimide (NCS) is expensive, and the removal of the succinimide byproducts formed during the reaction is also labor-intensive.

[0036] Furthermore, conventional methods for the synthesis of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile are associated with disadvantages such as harsh reaction conditions, long reaction times, low yields, and the use of toxic, expensive, or difficult-to-obtain reagents, rendering them impractical and subject to handling restrictions during synthesis. Therefore, conventional methods do not offer an efficient solution for the synthesis of 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile.

[0037] The present invention provides an improved process for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile. The structure of 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile is shown as Formula I:

[0038] The process of the present invention is simple, efficient, environmentally friendly, economical and leads to an improved yield and higher purity of 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile .

[0039] According to the present invention, the process for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile (formula I) comprises reacting the compound of formula II with a chlorinating agent in a liquid medium, followed by a reaction with a reducing agent, optionally in the presence of an organic base.

[0040] In a first embodiment, the present invention provides a two-step process for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile (formula I).

[0041] In a second embodiment, the present invention provides a one-step process for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile (Formula I).

[0042] According to the first embodiment of the present invention, the process for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile (formula I) comprises the following steps: a) Reacting a compound of formula II with a chlorinating agent in a liquid medium while stirring at a first predetermined temperature for a first predetermined period of time, in order to obtain a mixture of the compounds of formula III and formula I; and b) Reducing the mixtures of the compounds of formula III and formula I in the liquid medium using a reducing agent under stirring at a second predetermined temperature for a second predetermined period to obtain 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile (formula I).

[0043] According to the first embodiment of the present invention, the chlorinating agent is thionyl chloride.

[0044] According to the first embodiment of the present invention, 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 a preferred embodiment of the present invention, the molar ratio of the compound of formula II to the chlorinating agent is 1:2.5.

[0045] According to the first embodiment of the present invention, the liquid medium is selected from the group consisting of dimethylformamide (DMF), dimethylacetamide, sulfolane, dimethyl sulfoxide, N-methylpyrrolidine, acetonitrile, benzonitrile, and combinations thereof. In a preferred embodiment of the present invention, the liquid medium is selected from the group consisting of dimethylformamide (DMF).

[0046] According to the first embodiment of the present invention, the first predetermined temperature is in the range of 0 °C to 60 °C. In a preferred embodiment of the present invention, the first predetermined temperature is 30 °C.

[0047] According to the first embodiment of the present invention, the first predetermined period is in the range of 2 to 10 hours. In a preferred embodiment of the present invention, the first predetermined period is 4 hours.

[0048] According to the first embodiment of the present invention, 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 combinations thereof. In an exemplary embodiment of the present invention, the reducing agent is sodium metabisulfite.

[0049] According to the first embodiment of the present invention, the second predetermined temperature is in the range of 40 °C to 150 °C. In a preferred embodiment of the present invention, the second predetermined temperature is in the range of 80 °C to 100 °C. In a further preferred embodiment of the present invention, the second predetermined temperature is 90 °C.

[0050] According to the first embodiment of the present invention, the second predetermined period is in the range of 1 hour to 15 hours. In a preferred embodiment of the present invention, the second predetermined period is in the range of 4 hours to 8 hours. In a preferred embodiment of the present invention, the second predetermined period is 6 hours.

[0051] 4-Chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile is prepared according to the process of the present invention.

[0052] According to one embodiment of the present invention, the 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile has a purity of more than 90%.

[0053] According to one embodiment of the present invention, the purity of 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile is in the range of 90% to 96%. In a preferred embodiment of the present invention, the purity of 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile is 94%.

[0054] According to the first embodiment of the present invention, the yield of 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile is in the range of 60% to 80%. In a preferred embodiment of the present invention, the yield of 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile is 64.29%.

[0055] According to the second embodiment of the present invention, the process for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile (formula I) comprises reacting a compound of formula II with a chlorinating agent in a liquid medium with stirring at a first predetermined temperature for a first predetermined period to obtain a reaction mixture, followed by adjusting the pH of the reaction mixture by means of a base and subsequent addition of a reducing agent and stirring at a second predetermined temperature for a second predetermined period to obtain 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile (formula I).

[0056] According to the second embodiment of the present invention, the chlorinating agent is thionyl chloride.

[0057] According to one embodiment of the present invention, several reactions take place during the conversion of the compound of formula II to the compound of formula I, namely deprotection, dehydration, reduction, and chlorination using the chlorinating agent. In particular, the use of thionyl chloride in the process results in these several reactions, such as deprotection, dehydration, reduction, and chlorination, taking place in a single step, thereby making the process efficient and cost-effective.

[0058] The method of the present invention avoids the use of multiple reagents to carry out multiple reactions.

[0059] According to the second embodiment of the present invention, 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 a preferred embodiment of the present invention, the molar ratio of the compound of formula II to the chlorinating agent is 1:2.5.

[0060] According to the second embodiment of the present invention, the liquid medium is selected from the group consisting of dimethylformamide (DMF), dimethylacetamide, sulfolane, dimethyl sulfoxide, N-methylpyrrolidine, acetonitrile, benzonitrile, and combinations thereof. In a preferred embodiment of the present invention, the liquid medium is selected from the group consisting of dimethylformamide (DMF).

[0061] According to the second embodiment of the present invention, the first predetermined temperature is in the range of 0 °C to 60 °C. In a preferred embodiment of the present invention, the first predetermined temperature is 30 °C.

[0062] According to the second embodiment of the present invention, the first predetermined period is in the range of 2 to 10 hours. In a preferred embodiment of the present invention, the first predetermined period is 4 hours.

[0063] According to the second embodiment of the present invention, the base is selected from an organic base and an inorganic base.

[0064] The organic base is selected from the group consisting of triethylamine, diisopropylamine, pyridine, piperidine, and morpholine. In a preferred embodiment of the present invention, the organic base is triethylamine.

[0065] The inorganic base is selected from the group consisting of ammonia, potassium carbonate, sodium carbonate, potassium hydroxide and sodium hydroxide.

[0066] According to the second embodiment of the present invention, 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 combinations thereof. In an exemplary embodiment of the present invention, the reducing agent is sodium metabisulfite.

[0067] According to the second embodiment of the present invention, 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 a preferred embodiment of the present invention, the molar ratio of the compound of formula II to the reducing agent is 1:0.33.

[0068] According to the second embodiment of the present invention, the molar ratio of the compound of formula II to the base is in the range of 1:1 to 1:3. In a preferred embodiment of the present invention, the molar ratio of the compound of formula II to the base is in the range of 1:1.33.

[0069] According to the second embodiment of the present invention, the second predetermined temperature is in the range of 40 °C to 150 °C. In a preferred embodiment of the present invention, the second predetermined temperature is 50 °C.

[0070] According to the second embodiment of the present invention, the second predetermined period is in the range of 1 hour to 15 hours. In a preferred embodiment of the present invention, the second predetermined period is 2 hours.

[0071] According to the second embodiment of the present invention, the yield of 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile is in the range of 60% to 80%. In a preferred embodiment of the present invention, the yield of 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile is 77.15%.

[0072] 4-Chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile is prepared according to the process of the present invention.

[0073] According to one embodiment of the present invention, the 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile has a purity of more than 90%.

[0074] According to one embodiment of the present invention, the purity of 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile is in the range of 90% to 96%. In an exemplary embodiment of the present invention, the purity of 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile is 93%.

[0075] The present invention provides a simple, environmentally friendly and cost-effective process for the production of 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile with comparatively better yield and higher purity.

[0076] The foregoing description of the embodiments serves for illustration and is not intended to limit the scope of protection of the present invention. 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 deviation from the present invention, and all such modifications are deemed to be within the scope of protection of the present invention.

[0077] The present invention is described in more detail below with reference to the experiments listed below, which are presented solely for illustrative purposes and not to limit the scope of protection of the invention. The following experiments can be scaled up to an industrial / commercial scale, and the results obtained can be transferred to such an industrial scale. DETAILED DESCRIPTION OF EXPERIMENT EXAMPLE 1: A two-step process for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile (formula I) according to the present invention. Step (a) - Synthesis of a mixture of compounds of formula III and formula I:

[0078] A 2-liter, 4-necked round-bottom flask (RBF) was equipped with a condenser, a thermometer sleeve, a dropping funnel, and a stirrer. The RBF was charged with 200 g of 1-hydroxy-4-(4-methylphenyl)-3-oxide-1H-imidazol-2-carboxaldehyde oxime (formula II) and 600 ml of dimethylformamide (DMF) under stirring at 30 °C to obtain a first mixture. To this mixture, 250 g of thionyl chloride were added under stirring at 30 °C, and after the addition of thionyl chloride, the mixture was stirred at 30 °C for 4 hours to obtain a first product mixture.

[0079] To the initial product mixture, 50 ml of water were added, and the resulting mixture was slowly added to 2 liters of water and stirred for 2 hours to obtain solids. The resulting solid was filtered, washed with 200 ml of water, and dried to yield 180 g of a 50:50 mixture of compounds of formula III and formula I (mixing purity 83%). Step (b) - Synthesis of the compound of formula I:

[0080] A 2-liter, 4-necked rapid boiling boiler (RBB) was equipped with a condenser, a thermometer sleeve, a dropping funnel, and a stirrer. The RBF was charged with 170 g of the mixture of compounds from formula III and formula I, along with 500 ml of DMF, while stirring at 30 °C to obtain a second mixture. This second mixture was heated to 90 °C while stirring. Subsequently, 80 g of sodium metabisulfite were added while stirring at 90 °C, and stirring was continued at 90 °C for 6 hours to obtain a second product mixture.

[0081] To the second product mixture, 50 ml of water were added to obtain a homogeneous mass. The resulting homogeneous mass was slowly added to 2 liters of water and stirred for 2 hours to obtain solids. The resulting solid was filtered, washed with 200 ml of water, purified from aqueous acetone, and dried to obtain 120 g of the compound of formula I (purity 94%, yield 64.29%). EXAMPLE 2: A one-step process for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile (Formula I) according to the present invention

[0082] A 250 mL, 4-necked rapid pretreatment vessel (RBF) was equipped with a condenser, a thermometer sleeve, a dropping funnel, and a stirrer. The RBF was charged with 25 g of 1-hydroxy-4-(4-methylphenyl)-3-oxide-1H-imidazole-2-carbaldehyde oxime (formula II) and 75 mL of dimethylmethylcellulose (DMF) while stirring at 30 °C to obtain a mixture. Thionyl chloride was added to this mixture while stirring at 30 °C, and after the addition of thionyl chloride, 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 triethylamine. Subsequently, 7 g of sodium metabisulfite were added while stirring at 30 °C, and the resulting mass was heated to 50 °C while stirring and held for 2 hours to obtain a product mixture.

[0083] 20 ml of water were added to the product mixture, and the resulting mixture was slowly added to 250 ml of water and stirred for 2 hours to obtain solids. The resulting solid was filtered, washed with 20 ml of water, purified from aqueous acetone, and dried to obtain 18 g of the compound of formula I (purity 93%, yield 77.15%). COMPARISON EXAMPLES: Comparison example 1 (Conventional process for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile):

[0084] In a first step, 1-hydroxy-4-(4-methylphenyl)-3-oxide-1H-imidazol-2-carbaldehyde oxime (0.95 mol) and 750 mL of N,N-dimethylacetamide were mixed in a 5-liter flask and heated to 100 °C. Sodium metabisulfite (235 g, 1.2 mol) was added portionwise to obtain a mixture. The mixture was held at 100 °C for 8 hours to obtain a reaction mixture. The mixture was cooled to room temperature, and 2000 mL of water were added to precipitate the product. The solid was filtered off and washed with water and toluene, and the washed solids were dried. 139 g of crude (4-methylphenyl)-1H-imidazol-2-carbonitrile with a purity of 94.6% were obtained.

[0085] In a second step, 110 g of the product from the first step were mixed in a 500 mL flask with 55 mL of N,N-dimethylacetamide and 55 mL of acetonitrile. 86 g of N-chlorosuccinimide (NCS) were added, keeping the temperature below 25 °C. After complete addition, the mixture was stirred at 20 °C for 1 hour. 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, washed with water, suspended in toluene, filtered, and dried in a vacuum drying oven to yield 104 g of 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile.

[0086] The schematic representation for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile according to comparative example 2 is illustrated below as Scheme III:

[0087] From Example 1 and the comparative examples 1, it can be seen that the process for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile according to the present invention is a one-pot process with minimal reagent requirements (only catalytic amounts) and the final product 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile is obtained with comparatively better yield and purity.

[0088] Furthermore, the reaction conditions in the process of the present invention are milder compared to the process of the comparative example. In addition, the chlorination in the comparative example is carried out using N-chlorosuccinimide (NCS). NCS is expensive and also leads to the formation of succinimide byproducts during the reaction. The removal of such byproducts is problematic because it requires extensive work-up.

[0089] Furthermore, in the process of the present invention, several reactions such as deprotection, dehydration, reduction and chlorination take place in one step using only one reagent, namely thionyl chloride, which makes the process efficient, economical and environmentally friendly. TECHNICAL PROGRESS

[0090] The present invention, as described above, has several technical advantages, including, among others, the implementation of a process for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile, which; • Non-hazardous, inexpensive and readily available starting materials / reagents are used; • requires a comparatively shorter reaction time; • produces comparatively fewer impurities; • is commercially scalable; • is simple, efficient, cost-effective and environmentally friendly; and • 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile with comparatively higher purity and better yield.

[0091] The embodiments described herein, as well as their various features and advantageous details, are explained with reference to the non-limiting examples in the following description. Descriptions of known components and processing techniques are omitted to avoid unnecessarily obscuring the embodiments presented herein. The examples used here serve only to facilitate understanding of the embodiments and their applicability, and to enable those skilled in the art to implement them. Accordingly, the examples must not be interpreted as limiting the scope of protection of the embodiments described herein.

[0092] The foregoing description of the specific embodiments discloses the general nature of the embodiments described herein so completely that others, applying their current technical knowledge, can easily modify and / or adapt such specific embodiments for various applications without departing from the generally applicable concept. Therefore, such adaptations and modifications are to be understood as equivalent to the disclosed embodiments. It is to be understood that the language or terminology used herein serves for descriptive purposes and not to limit the scope of protection of the invention. While the embodiments described herein have been explained with reference to preferred embodiments, the person skilled in the art will recognize that the embodiments can be carried out with modifications in the sense and scope of those described herein.

[0093] The use of the terms "at least" or "at least one" indicates the use of one or more elements, components, or quantities as required in the embodiment of the invention to achieve one or more of the intended objectives or results. Although certain embodiments of the invention have been described, these embodiments serve only as examples and are not intended to limit the scope of protection of the invention. Variations or modifications to the formulation of this invention within the scope of protection of the invention may occur to a person skilled in the art after reviewing the present disclosure. Such variations or modifications are entirely within the meaning of this invention.

[0094] Any discussion of documents, actions, materials, devices, objects, or the like included in this description serves solely to provide context for the disclosure. It is not to be construed as an admission that any or all of these aspects form part of the prior art or constituted common general knowledge in the field relevant to the invention at the priority date of this application.

[0095] The specified numerical values ​​for various physical parameters, dimensions and quantities are only approximate values, and it is assumed that values ​​exceeding the specified numerical values ​​for the physical parameters, dimensions and quantities fall within the scope of protection of the invention, unless otherwise stated in the description.

[0096] Although considerable emphasis has been placed here on the specific features of the preferred embodiment, it should be noted that many additional features can be added and many modifications can be made to the preferred embodiment without departing from the principles of the invention. These and other modifications to the preferred embodiment of the invention will be apparent to the person skilled in the art from the present disclosure, and it should be expressly understood that the foregoing descriptions are to be interpreted merely as illustrative examples of the invention and not as limitations.

Claims

[1] Process for the preparation of 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile (formula I), wherein the said process comprises the reaction of a compound of formula II with a chlorinating agent in a liquid medium and subsequent reaction with a reducing agent, optionally in the presence of a base. [2] The method of claim 1, comprising the following steps: a) Reacting a compound of formula II with a chlorinating agent in a liquid medium while stirring at a first predetermined temperature for a first predetermined period of time, in order to obtain a mixture of the compounds of formula III and formula I; and b) Reducing the aforementioned mixtures of the compounds of formula III and formula I in a liquid medium using a reducing agent while stirring at a second predetermined temperature for a second predetermined period to obtain 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile (formula I). [3] The method according to claim 1 comprises reacting a compound of formula II with a chlorinating agent in a liquid medium with stirring at a first predetermined temperature for a first predetermined period to obtain a reaction mixture, followed by adjusting the pH of the reaction mixture using a base and subsequently adding a reducing agent and stirring at a second predetermined temperature for a second predetermined period to obtain 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile (formula I). [4] Method according to any one of claims 1 to 3, wherein the chlorinating agent is thionyl chloride. [5] Method according to any one of claims 1 to 3, wherein the molar ratio of the compound of formula II to the chlorinating agent is in the range of 1:1.5 to 1:

5. [6] Method according to any one of claims 1 to 3, wherein said liquid medium is selected from the group consisting of dimethylformamide (DMF), dimethylacetamide, sulfolane, dimethyl sulfoxide, N-methylpyrrolidine, acetonitrile, benzonitrile and combinations thereof. [7] Method according to claims 2 and 3, wherein the first predetermined temperature is in the range of 0 °C to 60 °C. [8] Method according to claims 2 and 3, wherein the first specified period is in the range of 2 hours to 10 hours. [9] Method according to claim 3, wherein said base is selected from an organic base and an inorganic base. [10] Method according to claim 9, wherein • the organic base is selected from the group consisting of triethylamine, diisopropylamine, pyridine, piperidine and morpholine; and • the inorganic base is selected from the group consisting of ammonia, potassium carbonate, sodium carbonate, potassium hydroxide and sodium hydroxide. [11] Method according to claims 1 to 3, wherein 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. [12] Method according to claim 3, wherein the molar ratio of the compound of formula II to the reducing agent is in the range of 1:0.1 to 1:

1. [13] Method according to claim 3, wherein the molar ratio of the compound of formula II to the base is in the range of 1:1 to 1:

3. [14] Method according to claim 2, wherein the second predetermined temperature is in the range of 40 °C to 150 °C. [15] Method according to claim 2, wherein the said second predetermined period is in the range of 1 hour to 15 hours. [16] Method according to claim 1, wherein the yield of 4-chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile is in the range of 60% to 80%. [17] 4-Chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile, prepared according to the process of any one of claims 1 to 16. [18] 4-Chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile according to claim 17 having a purity of more than 90%. [19] 4-Chloro-5-(4-methylphenyl)-1H-imidazol-2-carbonitrile according to claim 18, wherein the purity is in the range of 90% to 96%.