DESC:FIELD
The present disclosure relates to a process for the preparation of 3-chloro-2-hydrazinopyridine.
BACKGROUND
The background information herein below relates to the present disclosure but is not necessarily prior art.
3-chloro-2-hydrazinopyridine is an intermediate for the preparation of N-aryl pyrazole based carboxamides such as Chlorantraniliprole, Cyclaniliprole and Cyantraniliprole, which are useful agrochemicals.
Conventionally, the preparation of 3-chloro-2-hydrazinopyridine is carried out using methanol and ethanol, which are completely water miscible and hence difficult to recover from water.
There is, therefore, felt a need for a process for preparing 3-chloro-2-hydrazinopyridine that mitigates the drawbacks of conventional methods.
OBJECTS
Some of the objects of the present disclosure, which at least one embodiment herein satisfies, are as follows:
An object of the present disclosure is to ameliorate one or more problems of the prior art or to at least provide a useful alternative.
Another object of the present disclosure is to provide a process for the preparation of 3-chloro-2-hydrazinopyridine with greater yield and high purity.
Yet another object of the present disclosure is to provide a process for the preparation of 3-chloro-2-hydrazinopyridine that is simple, efficient and economical.
Still another object of the present disclosure is to provide a process for the preparation of 3-chloro-2-hydrazinopyridine that is environmental friendly.
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-chloro-2-hydrazinopyridine. The process comprises dissolving 2,3-dichloropyridine in a fluid medium under stirring to obtain a solution. At least one inorganic base is added to the solution under stirring to obtain a slurry. Aqueous hydrazine is added to the slurry under stirring over a first predetermined time period to obtain a reaction mass. The reaction mass is heated at a predetermined temperature for a second predetermined time period to obtain a product mixture comprising crude 3-chloro-2-hydrazinopyridine. 3-chloro-2-hydrazinopyridine is separated from the product mixture to obtain pure 3-chloro-2-hydrazinopyridine having a purity greater than 95% and a yield = 85%.
DETAILED DESCRIPTION
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, known processes or well-known apparatus or 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 are 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.
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.
3-chloro-2-hydrazinopyridine is an intermediate used in the preparation of N-aryl pyrazole based carboxamides such as Chlorantraniliprole, Cyclaniliprole and Cyantraniliprole, which are useful agrochemicals. The structural formula for 3-chloro-2-hydrazinopyridine is as given below.

The present disclosure provides a simple process for the preparation of 3-chloro-2-hydrazinopyridine.
The schematic representation of the process for the preparation of 3-chloro-2-hydrazinopyridine, is as given below:

The process for preparing 3-chloro-2-hydrazinopyridine is described in detail herein below.
In the first step, 2,3-dichloropyridine is dissolved in a fluid medium under stirring to obtain a solution.
The fluid medium is selected from 1-methoxy-2-(2-methoxyethoxy)ethane (commonly known as diglyme), monoglyme, methoxyethanol, 2-ethoxyethanol, 2-butoxyethanol and n-butanol. In an exemplary embodiment of the present disclosure, the fluid medium is diglyme
Diglyme (dimethyl ether of diethylene glycol) is an organic solvent having a high boiling point. It is a clear and colorless liquid that is miscible in water, alcohols, diethyl ether, and hydrocarbon solvents. The stability of diglyme at high pH values makes it an excellent solvent for reactions with strong bases or reactions that require high temperatures.
The stability of diglyme has driven the attention of the inventors of the present disclosure to use diglyme as one of the fluid media in the process for the preparation of 3-chloro-2-hydrazinopyridine. The inventors of the present disclosure suprisingly found that when diglyme is used as a solvent, the yield and the purity of 3-chloro-2-hydrazinopyridine significantly increased as compared to the solvents used in the conventional process of preparing 3-chloro-2-hydrazinopyridine.
In accordance with the present disclosure, a molar ratio of 2,3-dichloropyridine to the fluid medium is in the range of 1:2 to 1:4. In an exemplary embodiment of the present disclosure, the molar ratio of 2,3-dichloropyridine to diglyme is 1:3.
In the next step, at least one inorganic base is added to the solution under stirring to obtain a slurry.
The inorganic base is at least one selected from the group consisting of potassium carbonate, sodium carbonate, sodium bicarbonate, potassium bicarbonate, sodium hydroxide, potassium hydroxide, magnesium carbonate, lithium carbonate, caesium carbonate and calcium carbonate.
In the next step, aqueous hydrazine is added to the slurry under stirring over a first predetermined time period to obtain a reaction mass.
In accordance with the present disclosure, a molar ratio of 2,3-dichloropyridine to the aqueous hydrazine is in the range of 1:1 to 1:6. In an exemplary embodiment of the present disclosure, the molar ratio of 2,3-dichloropyridine to hydrazine is 1:3.
In an embodiment of the present disclosure, a concentration of hydrazine in the aqueous hydrazine is in the range of 50 wt% to 55 wt%. In an exemplary embodiment of the present disclosure, the concentration of hydrazine in the aqueous hydrazine is 50 wt%.
In an embodiment of the present disclosure, the first predetermined time period is in the range of 15 minutes to 60 minutes. In an exemplary embodiment of the present disclosure, the first predetermined time period is 30 minutes. In another exemplary embodiment of the present disclosure, the first predetermined time period is 45 minutes.
In the next step, the reaction mass is heated at a predetermined temperature for a second predetermined time period to obtain a product mixture comprising crude 3-chloro-2-hydrazinopyridine. The reaction is monitored by using HPLC.
In an embodiment of the present disclosure, the predetermined temperature is in the range of 80 °C to 150 °C. In an exemplary embodiment of the present disclosure, the predetermined temperature is 100 °C. In another exemplary embodiment of the present disclosure, the predetermined temperature is 110 °C.
In an embodiment of the present disclosure, the second predetermined time period is in the range of 10 hours to 25 hours. In an exemplary embodiment of the present disclosure, the second predetermined time period is 12 hours. In another exemplary embodiment of the present disclosure, the second predetermined time period is 18 hours. In yet another exemplary embodiment of the present disclosure, the second predetermined time period is 22 hours. In still another exemplary embodiment of the present disclosure, the second predetermined time period is 24 hours.
In the next step, 3-chloro-2-hydrazinopyridine is separated from the product mixture to obtain pure 3-chloro-2-hydrazinopyridine having a purity greater than 95% and a yield = 85%.
In accordance with the embodiments of the present disclosure, the step of separating 3-chloro-2-hydrazinopyridine is carried out by cooling said product mixture to a temperature in the range of 0 °C to 10 °C followed by filtering, washing and drying to obtain pure 3-Chloro-2-hydrazinopyridine having a purity greater than 95% and a yield = 85%.
In an embodiment of the present disclosure, 3-chloro-2-hydrazinopyridine is obtained having a purity in the range of 90 to 99.97% and a yield in the range of 85% to 98%.
The present disclosure provides an alternative process for preparing 3-chloro-2-hydrazinopyridine by using high boiling solvents.
In accordance with the embodiments of the present disclosure, the process for preparing 3-chloro-2-hydrazinopyridine is carried out by using diglyme as fluid medium. Diglyme is stable at high pH values, and therefore is an excellent choice as a fluid medium for reactions that use strong bases. Further, diglyme is an organic fluid medium having a high boiling point and therefore can be used for carrying out reactions that require high temperatures. Additionally, 3-chloro-2-hydrazinopyridine can be crystallized from diglyme at low temperature, thereby providing it in greater yields and with high purity. 3-chloro-2-hydrazinopyridine is used as an intermediate in the synthesis of N-aryl pyrazole based carboxamides such as chlorantraniliprole, Cyclaniliprole and cyantraniliprole. Diglyme is easily available, inexpensive and less toxic. As a result of using inexpensive and easily available diglyme as fluid medium, the process of the present disclosure is cost efficient and economical.
Thus, the present disclosure avoids the use of expensive and toxic organic solvents for preparing 3-chloro-2-hydrazinopyridine. Hence, the present disclosure saves on the cost of procuring expensive organic solvents and makes the process efficient, economic and environmental friendly.
The foregoing description of the embodiments has been provided for purposes of illustration and 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 illustrated herein below with the help of the following experiments. The experiments used herein are intended merely to facilitate an understanding of the 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 experiments should not be construed as limiting the scope of embodiments herein. These laboratory scale experiments can be scaled up to industrial/commercial scale and the results obtained can be extrapolated to industrial/commercial scale.
EXPERIMENTAL DETAILS
EXAMPLE 1: Preparation of 3-chloro-2-hydrazinopyridine
2,3-dichloropyridine (740 g) was dissolved in diglyme (2 litres) under stirring to obtain a solution. Potassium carbonate (675 g) was added to the solution under stirring to obtain a slurry. Aqueous Hydrazine (960 g, 50% aq. Soln) was slowly added to the slurry under stirring over 30 minutes to obtain a reaction mass. The reaction mass was heated at 118 °C for 12 hours to obtain a product mixture comprising crude 3-chloro-2-hydrazinopyridine. The reaction was monitored by using HPLC. 3-chloro-2-hydrazinopyridine was separated from the product mixture, washed and dried to obtain pure 3-chloro-2-hydrazinopyridine. (Dry weight = 671 g; HPLC purity = 96%; yield on purity = 90%).
EXAMPLE 2: Preparation of 3-chloro-2-hydrazinopyridine (Using recovered and distilled diglyme)
2,3-Dichloropyridine (888 gms) was added to diglyme (recovered and distilled) (2.4 litres) under stirring to obtain a solution. Potassium carbonate (812 gms) was added to the sloution under stirring to obtain a slurry. Aqueous hydrazine (1130 gms, 51% aq. Soln) was added to the slurry under stirring, over 30 minutes to obtain a reaction mass. The reaction mass was heated at 113 °C for 18 hours to obtain a product mixture comprising crude 3-chloro-2-hydrazinopyridine. The reaction was monitored by using HPLC. 3-chloro-2-hydrazinopyridine was separated from the product mixture, washed and dried to obtain pure 3-chloro-2-hydrazinopyridine in 98% yield and with 98% purity.
EXAMPLE 3: Preparation of 3-chloro-2-hydrazinopyridine
2,3-dichloropyridine (740 g) was dissolved in diglyme (2 litres) under stirring to obtain a solution. Potassium carbonate (666 g) was added to the solution under stirring to obtain a slurry. Aqueous Hydrazine (960 g, 50% aq. Soln) was slowly added to the slurry under stirring over 30 minutes to obtain a reaction mass. The reaction mass was heated at 100 °C for 12 hours to obtain a product mixture comprising crude 3-chloro-2-hydrazinopyridine. The reaction was monitored byusing HPLC. The crude 3-chloro-2-hydrazinopyridine was separated from the product mixture, washed and dried to obtain pure 3-chloro-2-hydrazinopyridine. (Dry weight = 674 g; HPLC purity = 98.82%; yield on purity = 94%).
EXAMPLE 4: Preparation of 3-chloro-2-hydrazinopyridine
2,3-dichloropyridine (740 g) was dissolved in diglyme (2 litres) under stirring to obtain a solution. Sodium carbonate (520 g) was added to the solution under stirring to obtain a slurry. Aqueous Hydrazine (960 g, 50% aq. Solution) was slowly added to the slurry under stirring over 45 minutes to obtain a reaction mass. The reaction mass was heated at 110 °C for 22 hours to obtain a product mixture comprising crude 3-chloro-2-hydrazinopyridine. The reaction was monitored by using HPLC. The crude 3-chloro-2-hydrazinopyridine was separated from the product mixture, washed and dried to obtain pure 3-chloro-2-hydrazinopyridine. (Dry weight = 663 g; HPLC purity = 99.97%; yield on purity = 92%).
EXAMPLE 5: Preparation of 3-chloro-2-hydrazinopyridine
2,3-dichloropyridine (74 g) was dissolved in 2-butoxyethanol (200 ml) under stirring to obtain a solution. Potassium carbonate (69 g) was added to the solution under stirring to obtain a slurry. Aqueous Hydrazine (96 g, 50% aq. Solution) was slowly added to the slurry under stirring over 45 minutes to obtain a reaction mass. The reaction mass was heated at 118 °C for 24 hours to obtain a product mixture comprising crude 3-Chloro-2-hydrazinopyridine. The reaction was monitored by using HPLC. The crude 3-chloro-2-hydrazinopyridine was separated from the product mixture, washed and dried to obtain pure 3-chloro-2-hydrazinopyridine (Dry weight = 64 g; HPLC purity = 95%; yield on purity = 85%).
COMPARATIVE EXAMPLE: Preparation of 3-chloro-2-hydrazinopyridine (using ethanol as a fluid medium)
2,3-dichloropyridine (15 g) was dissolved in commercial ethanol (100 ml) under stirring to obtain a solution. Aqueous Hydrazine (38 g, 51% aq. Solution) was added to the solution under stirring to obtain a reaction mass. The reaction mass was heated at 78 °C for 12 hours to obtain a product mixture comprising crude 3-chloro-2-hydrazinopyridine. The reaction was monitored by using HPLC. The crude 3-chloro-2-hydrazinopyridine was separated from the product mixture, washed and dried to obtain pure 3-chloro-2-hydrazinopyridine (Dry weight = 5.6 g; HPLC purity = 90%; yield on purity = 35%).
The present disclosure thus provides a simple, efficient and environment friendly process for the preparation of 3-chloro-2-hydrazinopyridine with a greater yield and better purity.
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-chloro-2-hydrazinopyridine, wherein:
• the process provides 3-chloro-2-hydrazinopyridine with high purity and in greater yields;
• the process is simple, efficient and environment friendly; and
• fluid medium can be separated, distilled and reused.
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 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.
,CLAIMS:WE CLAIM:
1. A process for preparing 3-chloro-2-hydrazinopyridine, said process comprising the following steps:
(a) dissolving 2,3-dichloropyridine in a fluid medium under stirring to obtain a solution;
(b) adding at least one inorganic base to said solution under stirring to obtain a slurry;
(c) adding aqueous hydrazine to said slurry under stirring for a first predetermined time period to obtain a reaction mass;
(d) heating said reaction mass at a predetermined temperature for a second predetermined time period to obtain a product mixture comprising crude 3-chloro-2-hydrazinopyridine; and
(e) separating 3-chloro-2-hydrazinopyridine from said product mixture to obtain 3-chloro-2-hydrazinopyridine having a purity greater than 95% and a yield = 85%.
2. The process as claimed in claim 1, wherein said fluid medium is selected from diglyme (1-methoxy-2-(2-methoxyethoxy)ethane), monoglyme, 2-methoxyethanol, 2-ethoxyethanol, 2-butoxyethanol and n-butanol.
3. The process as claimed in claim 1, wherein a molar ratio of the 2,3-dichloropyridine to said fluid medium is in the range of 1:2 to 1:4.
4. The process as claimed in claim 1, wherein said inorganic base is at least one selected from the group consisting of potassium carbonate, sodium carbonate, sodium bicarbonate, potassium bicarbonate, sodium hydroxide, potassium hydroxide, magnesium carbonate, lithium carbonate, caesium carbonate and calcium carbonate.
5. The process as claimed in claim 1, wherein a concentration of hydrazine in said aqueous hydrazine is in the range of 50 wt% to 55 wt%.
6. The process as claimed in claim 1, wherein a molar ratio of the 2,3-dichloropyridine to said hydrazine is in the range of 1:1 to 1:6.
7. The process as claimed in claim 1, wherein said first predetermined time period is in the range of 15 minutes to 60 minutes.
8. The process as claimed in claim 1, wherein said predetermined temperature is in the range of 80 °C to 150 °C.
9. The process as claimed in claim 1, wherein said second predetermined time period is in the range of 10 hours to 25 hours.