Claims:WE CLAIM:
1. A process for preparing cartap hydrochloride, said process comprising the following steps:
a. reacting a compound selected from 1,3-dithiocyanato-2-(dimethylamino)propane and its hydrochloride salt with a predetermined amount of a first alcohol in a fluid medium and optionally by using an inorganic acid at a first predetermined temperature to obtain a first reaction mixture;
b. cooling said first reaction mixture to a second predetermined temperature followed by slowly adding a predetermined amount of thionyl chloride for a first predetermined time period to obtain a second reaction mixture;
c. heating said second reaction mixture to a third predetermined temperature for simultaneously removing water and by-products to obtain a reaction mass;
d. cooling said reaction mass to a fourth predetermined temperature followed by adding a second alcohol and refluxing for a second predetermined time period to obtain a slurry;
e. cooling said slurry to a fifth predetermined temperature followed by filtration to obtain a wet cake and a first filtrate; and
f. washing said wet cake with at least one third alcohol followed by drying to obtain said cartap hydrochloride and a second filtrate.

2. The process as claimed in claim 1, wherein
a. mixing said first filtrate and said second filtrate to obtain a mixture;
b. distilling said mixture for recovering said alcohol and said fluid medium to obtain a resultant mixture; and
c. mixing said resultant mixture with a fourth alcohol and cooled to sixth predetermined temperature followed by filtration to obtain said cartap hydrochloride.

3. The process as claimed in claim 1, wherein said 1,3-dithiocyanato-2-(dimethyl amino)propane hydrochloride salt contains 1,2-dithiocyanato-3-(dimethylamino)propane hydrochloride salt in an amount in the range of 0 to 10%.

4. The process as claimed in claim 1, wherein said 1,3-dithiocyanato-2-(dimethyl amino)propane contains 1,2-dithiocyanato-3-(dimethylamino)propane in an amount in the range of 0 to 10%.

5. The process as claimed in claim 1, wherein said first alcohol, said second alcohol, said third alcohol, and said fourth alcohol are same or different and are selected from the group consisting of methanol, ethanol, propanol, isopropanol, n-butenol, t-butenol, pentenol, and isopentenol.

6. The process as claimed in claim 1, wherein said fluid medium is at least one selected from the group consisting of toluene, dichloroethane, xylene, chlorobenzene, and bromobenzene.

7. The process as claimed in claim 1, wherein said inorganic acid is aqueous HCl.

8. The process as claimed in claim 1, wherein said first predetermined temperature is in the range of 25°C to 40°C and said first predetermined time period is in the range of 1 hour to 5 hours.

9. The process as claimed in claim 1, wherein said second predetermined temperature is in the range of 0°C to 25°C and said second predetermined time period is in the range of 30 minutes to 120 minutes.

10. The process as claimed in claim 1, wherein said third predetermined temperature is in the range of 70°C to 110 °C.

11. The process as claimed in claim 1, wherein said fourth predetermined temperature is in the range of 50°C to 80°C.

12. The process as claimed in claim 1, wherein said fifth predetermined temperature is in the range of 15°C to 25°C.

13. The process as claimed in claim 1, wherein said sixth predetermined temperature is in the range of 20°C to 35°C.

14. The process as claimed in claim 1, wherein a mole ratio of said compound selected from 1,3-dithiocyanato-2-(dimethylamino) propane and its hydrochloride salt to said first alcohol is in the range of 1:4 to 1:10.

15. The process as claimed in claim 1, wherein a mole ratio of said compound selected from 1,3-dithiocyanato-2-(dimethylamino) propane and its hydrochloride salt to said thionyl chloride is in the range of 1:1 to 1:5.

16. The process as claimed in claim 1, wherein said by-products are sulphur dioxide and methyl chloride.

17. The process as claimed in claim 1, wherein said first alcohol, said second alcohol, said third alcohol, said fourth alcohol, and said fluid media are recovered.
, Description:FIELD
The present disclosure relates to a process for the preparation of cartap hydrochloride.
BACKGROUND
The background information hereinbelow relates to the present disclosure but is not necessarily prior art.
Cartap is a thiocarbamate insecticide, having the chemical formula C7H16ClN3O2S2 [CAS No. 15263-53-3]. It is commonly used in the hydrochloride form (Cartap hydrochloride: C7H15N3O2S3HCl). The chemical name of Cartap hydrochloride (I) is S-(3-carbamoylsulfanyl-2-(dimethylamino) propyl) carbamothioate hydrochloride.

Cartap hydrochloride (I)
Cartap hydrochloride is a nereistoxin analog that effectively eliminates insects through its contact, systemic and stomach action. It is essentially a contact insecticide and is highly effective against both chewing and sucking pests, resulting in paralysis. Cartap hydrochloride is categorized as an effective, relatively low-toxic, and low-residue insecticide. Cartap hydrochloride is preferred because of its broad-spectrum activity.
Conventional processes for the preparation of cartap hydrochloride are associated with disadvantages such as low yield, use of dry HCl gas for carrying out the hydrolysis of dithiocyanato intermediate compound, and the like. The use of dry HCl gas on a large scale is associated with drawbacks such as increased production costs and handling issues. Further, hydrogen chloride (HCl) gas has a suffocating odour and is harmful to the respiratory tract of the person carrying out the reaction.
There is, therefore, felt a need to provide a process for preparing cartap hydrochloride that mitigates the aforestated drawbacks.
OBJECTS
Some of the objects of the present disclosure, which at least one embodiment herein satisfies, are as follows:
It is an object of the present disclosure to ameliorate one or more problems of the prior art or to at least provide a useful alternative.
Another object of the present disclosure is to provide a process for the preparation of cartap hydrochloride.
Another object of the present disclosure is to provide a process for the preparation of cartap hydrochloride with a comparatively better yield and purity.
Yet another object of the present disclosure is to provide a process for the preparation of cartap hydrochloride using reagents which can be handled easily on a large scale.
Still another object of the present disclosure is to provide a process for the preparation of cartap hydrochloride by avoiding the use of dry HCl gas.
Still another object of the present disclosure is to provide a simple and cost-efficient process for the preparation of cartap hydrochloride.
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 cartap hydrochloride. The process comprises reacting a compound selected from 1,3-dithiocyanato-2- (dimethylamino) propane and its hydrochloride salt with a predetermined amount of first alcohol in a fluid medium and optionally by using an inorganic acid at a first predetermined temperature to obtain a first reaction mixture. The first reaction mixture is cooled to a second predetermined temperature followed by slowly adding a predetermined amount of thionyl chloride for a first predetermined time period to obtain a second reaction mixture. The second reaction mixture is heated to a third predetermined temperature for simultaneous removal of water and by-products to obtain a reaction mass. The reaction mass is cooled to a fourth predetermined temperature followed by adding a second alcohol and refluxed for a second predetermined time period to obtain a slurry. The slurry is cooled to a fifth predetermined temperature followed by filtration to obtain a wet cake and a first filtrate. The wet cake is washed with at least one third alcohol followed by drying to obtain the cartap hydrochloride and a second filtrate.
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, 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.
Cartap hydrochloride is a nereistoxin analog that effectively eliminates insects through its contact, systemic and stomach action. It is essentially a contact insecticide and is highly effective against both chewing and sucking pests, resulting in paralysis. Cartap hydrochloride is categorized as an effective, relatively low-toxic, and low-residue insecticide. Cartap hydrochloride is preferred because of its broad-spectrum activity.
Conventional processes for the preparation of cartap hydrochloride are associated with disadvantages such as low yield, use of dry HCl gas for carrying out the hydrolysis of thiocyanato intermediate compound. The use of dry HCl gas on a large scale is associated with drawbacks such as increased production costs and handling issues. Further, hydrogen chloride (HCl) gas has a suffocating odour and is harmful to the respiratory tract of the person carrying out the reaction.
The present disclosure provides an improved process for the preparation of cartap hydrochloride.
The process of the present disclosure is simple, environment friendly, economical, resulting in improved yields and higher purity. The process of the present disclosure discloses a process for the preparation of cartap hydrochloride(I):

Chemical formula: C7H16ClN3O2S2
Molar mass: 237.3
the process comprising the following steps:
a. reacting a compound selected from 1,3-dithiocyanato-2-(dimethylamino)propane and its hydrochloride salt with a predetermined amount of first alcohol in a fluid medium and optionally by using an inorganic acid at a first predetermined temperature to obtain a first reaction mixture;
b. cooling the first reaction mixture to a second predetermined temperature followed by slowly adding a predetermined amount of thionyl chloride for a first predetermined time period to obtain a second reaction mixture;
c. heating the second reaction mixture to a third predetermined temperature for simultaneously removing water and by-products to obtain a reaction mass;
d. cooling the reaction mass to a fourth predetermined temperature followed by adding a second alcohol and refluxing for a second predetermined time period to obtain a slurry;
e. cooling the slurry to a fifth predetermined temperature followed by filtration to obtain a wet cake and a first filtrate; and
f. washing the wet cake with at least one third alcohol followed by drying to obtain the cartap hydrochloride and a second filtrate;
The process is described in detail
In a first step, the compound selected from 1,3-dithiocyanato-2-(dimethylamino) propane and its hydrochloride salt is reacted with a predetermined amount of first alcohol in at least one fluid medium and optionally by using an inorganic acid at a first predetermined temperature to obtain a first reaction mixture.
In accordance with an embodiment of the present disclosure, the 1,3-dithiocyanato-2-(dimethylamino) propane contains 1,2-dithiocyanato-3-(dimethylamino)propane in an amount in the range of 0 to 10%. In an exemplary embodiment of the present disclosure, 1,3-dithiocyanato-2-(dimethylamino) propane is employed. In another exemplary embodiment of the present disclosure, 1, 3-dithiocyanato-2-(dimethylamino) propane is a mixture of 1, 3-dithiocyanato-2-(dimethylamino) propane (90% w/w) and 1, 2-dithiocyanato-3-(dimethylamino) propane (10% w/w) is employed.
In accordance with an embodiment of the present disclosure, the 1,3-dithiocyanato-2-(dimethylamino) propane hydrochloride salt contains 1,2-dithiocyanato-3-(dimethylamino)propane hydrochloride salt in an amount in the range of 0 to 10%. In an exemplary embodiment of the present disclosure, 1,3-dithiocyanato-2- (dimethylamino) propane hydrochloride salt is employed. In another exemplary embodiment of the present disclosure, 1, 3-dithiocyanato-2-(dimethylamino) propane hydrochloride salt is a mixture of 1, 3-dithiocyanato-2-(dimethylamino) propane hydrochloride salt (90% w/w) and 1, 2-dithiocyanato-3-(dimethylamino) propane hydrochloride salt (10% w/w) is employed.
In accordance with an embodiment of the present disclosure, the first alcohol is selected from the group consisting of methanol, ethanol, propanol, isopropanol, n-butenol, t-butenol, pentenol, and isopentenol. In an exemplary embodiment of the present disclosure, the first alcohol is methanol.
In accordance with an embodiment of the present disclosure, the fluid medium is selected from the group consisting of toluene, dichloroethane, xylene, chlorobenzene, and bromobenzene. In an exemplary embodiment of the present disclosure, the fluid medium is toluene. In another exemplary embodiment of the present disclosure, the fluid medium is dichloroethane.
In accordance with an embodiment of the present disclosure, the inorganic acid is aqueous HCl. In accordance with an embodiment of the present disclosure, the concentration of inorganic acid is in the range of 25% w/w to 30% w/w HCl. In an exemplary embodiment of the present disclosure, the concentration of inorganic acid is 30% w/w HCl.
In accordance with an embodiment of the present disclosure, the first predetermined temperature is in the range of 25°C to 40°C, preferably in the range of 30°C to 35°C. In an exemplary embodiment of the present disclosure, the first predetermined temperature is 32°C.
In accordance with an embodiment of the present disclosure, the mole ratio of the compound selected from 1,3-dithiocyanato-2-(dimethylamino) propane and its hydrochloride salt to the first alcohol is in the range of 1:4 to 1:10. In an exemplary embodiment of the present disclosure, the mole ratio is 1:4.94. In another exemplary embodiment of the present disclosure, the mole ratio is 1:6.18. In yet another exemplary embodiment of the present disclosure, the mole ratio is 1:8.65.
In a second step, the first reaction mixture is cooled to a second predetermined temperature followed by slowly adding a predetermined amount of thionyl chloride for a first predetermined time period to obtain a second reaction mixture.
In accordance with an embodiment of the present disclosure, the second predetermined temperature is in the range of 0.0°C to 25°C. In an exemplary embodiment of the present disclosure, the second predetermined temperature is below 25.0°C.
In accordance with an embodiment of the present disclosure, the first predetermined time period is in the range of 3 hours to 8 hours. In an exemplary embodiment of the present disclosure, the first predetermined time period is 4 hours.
In accordance with an embodiment of the present disclosure, the mole ratio of the compound selected from 1, 3-dithiocyanato-2-(dimethylamino) propane and its hydrochloride salt to the thionyl chloride is in the range of 1:1 to 1:5. In an exemplary embodiment of the present disclosure, the mole ratio is 1:2. In another exemplary embodiment of the present disclosure, the mole ratio is 1:2.5. In another exemplary embodiment of the present disclosure, the mole ratio is 1:4.
In a third step, the second reaction mixture is heated to a third predetermined temperature for simultaneously removing water and by-products to obtain a reaction mass.
In accordance with an embodiment of the present disclosure, the third predetermined temperature is in the range of 70°C to 110°C. In an exemplary embodiment, the third predetermined temperature is 104°C. In another exemplary embodiment of the present disclosure, the third predetermined temperature is 82°C.
In a fourth step, the reaction mass is cooled to a fourth predetermined temperature followed by the addition of at least one second alcohol and refluxed for a second predetermined time period to obtain a slurry.
In accordance with an embodiment of the present disclosure, the fourth predetermined temperature is in the range of 50°C to 80°C. In an exemplary embodiment of the present disclosure, the fourth predetermined temperature is 65°C.
In accordance with an embodiment of the present disclosure, the second alcohol is selected from the group consisting of methanol, ethanol, propanol, isopropanol, n-butenol, t-butenol, pentenol, and isopentenol. In an exemplary embodiment of the present disclosure, the second alcohol is methanol.
In accordance with an embodiment of the present disclosure, the second predetermined time period is in the range of 30 minutes to 120 minutes. In an exemplary embodiment of the present disclosure, the second predetermined time period is 60 minutes.
In a fifth step, the slurry is cooled to a fifth predetermined temperature followed by filtration to obtain a wet cake and a first filtrate.
In accordance with an embodiment of the present disclosure, the fifth predetermined temperature is in the range of 15°C to 25°C. In an exemplary embodiment of the present disclosure, the fifth predetermined temperature is 20°C.
In a final step, the wet cake is washed with at least one third alcohol followed by drying to obtain the cartap hydrochloride (crop I) and a second filtrate.
In accordance with an embodiment of the present disclosure, the third alcohol is selected from the group consisting of methanol, ethanol, propanol, isopropanol, n-butenol, t-butenol, pentenol, and isopentenol. In an exemplary embodiment of the present disclosure, the third alcohol is methanol.
In accordance with an embodiment of the present disclosure, the first filtrate and the second filtrate are combined to obtain a mixture.
In accordance with an embodiment of the present disclosure, the alcohol, and the fluid medium are recovered from the mixture of the first filtrate and the second filtrate by distillation to obtain a resultant mixture.
In an exemplary embodiment of the present disclosure, the alcohol and the fluid medium recovered are methanol and toluene. In another exemplary embodiment of the present disclosure, the alcohol and the fluid medium recovered are methanol and dichloroethane.
In accordance with an embodiment of the present disclosure, the resultant mixture is mixed with at least one fourth alcohol and cooled to a sixth predetermined temperature followed by filtration to obtain the cartap hydrochloride (crop-II).
In accordance with an embodiment of the present disclosure, the fourth alcohol is selected from the group consisting of methanol, ethanol, propanol, isopropanol, n-butenol, t-butenol, pentenol, and isopentenol. In an exemplary embodiment of the present disclosure, the fourth alcohol is methanol.
In accordance with an embodiment of the present disclosure, the sixth predetermined temperature is in the range of 20°C to 35°C. In an exemplary embodiment of the present disclosure, the sixth predetermined temperature is 30°C.
The process of the present disclosure is simple, avoids the use of dry HCl gas for preparing Cartap hydrochloride. The preparation of dry HCl gas in the laboratory requires a specialized experimental setup. Further, it is very difficult to handle dry hydrochloric acid gas on a large scale. Hydrogen chloride (HCl) gas has a suffocating odour and is harmful to the respiratory tract of the person carrying out the reaction. The process of the present disclosure is safe and environment friendly.
The yield of the cartap hydrochloride obtained by the process of the present disclosure is in the range of 82% to 90%, comparatively higher in respect of the conventional processes. The purity of the cartap hydrochloride obtained by the process of the present disclosure is >99.0 %.
The alcohol, toluene, and dichloroethane employed in the process of the present disclosure are separated, recovered, and recycled from the reaction process. Hence, the process of the present disclosure is economic and environment friendly.
The by-products such as sulphur-dioxide and methyl chloride formed during the process of the present disclosure are also scrubbed & compressed out. Therefore, the process of the present disclosure is environment friendly and suitable for industrial applications.
The purity of crop-I of cartap hydrochloride in accordance with the present disclosure is above 99%. The yield of crop-I of cartap hydrochloride in accordance with the present disclosure is in the range of 75% to 90%.
The purity of crop-II of cartap hydrochloride as per the process of the present disclosure is above 87% to 90%. The yield of crop-II of cartap hydrochloride as per the process of the present disclosure is in the range of 5 wt% to10 wt% which will be recycled in the process.
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 purposes 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:
The reactor was equipped with an overhead stirrer, Dean and Stark system, thermometer, and glass condenser. 300 ml of toluene, 200 ml of methanol, and 100 ml of 30 % w/w HCl were charged into a reactor and heated to 32°C, followed by adding 237.5 gm of (98.0 % purity) 1, 3-dithiocyanato-2- (dimethylamino) propane hydrochloride salt to obtain a first reaction mixture. The first reaction mixture was cooled to 15°C, maintaining the temperature below 25°C, 238.0 gm of thionyl chloride was slowly added over a period of 4 hours to obtain a second reaction mixture. The so obtained second reaction mixture was equilibrated for 1 hour, and the temperature was raised up to 104°C (azeotropic reflux) with simultaneous removal of water and by-products to obtain a reaction mass. The azeotropic distillation was continued till there was no more water separation at Dean and stark apparatus. The addition of thionyl chloride and the rise in the temperature leads to the evolution of gases i.e., SO2 and methyl chloride. The SO2 generated was scrubbed with water, and the methyl chloride was passed through the brine cooled condenser and collected as a liquid. The reaction mass was cooled to 65°C followed by the addition of 1000 ml of methanol and refluxed for 1.0 hour to obtain a slurry. The slurry was cooled to 20°C followed by filtration to obtain a wet cake and a first filtrate. The so obtained wet cake was washed with 200 ml of methanol and dried to obtain the cartap hydrochloride and a second filtrate. The purity of Cartap hydrochloride was >99.0 % and the yield was 238.0 gram (87.0 m %) (Crop I).
The first filtrate and the second filtrate were mixed to obtain a filtrate mixture. The methanol and toluene were recovered from the mixture of the first filtrate and the second filtrate by distillation till the precipitation of bottom mass to obtain a resultant mixture. The so obtained resultant mixture was mixed with 100 ml of methanol and cooled to 30°C followed by filtration to obtain cartap hydrochloride (crop II). The cartap hydrochloride (crop II) can be recycled in the next batch.
The purity of Cartap hydrochloride (crop-II) was 90.0 % and the yield was 13.7 gram (5.0 m %).
Example 2:
The reactor was equipped with an overhead stirrer, Dean and Stark system, thermometer, and glass condenser. 350 ml of toluene, 200 ml of methanol, and 100 ml of 30 % w/w HCl were charged into a reactor and heated to 32°C, followed by adding 237.5 gm of (98.0 % purity) 1, 3-dithiocyanato-2-(dimethylamino) propane hydrochloride salt and 13.7 grams of crop-II cartap hydrochloride (obtained in example 1) to obtain a first reaction mixture. The first reaction mixture was cooled to 15°C, maintaining the temperature below 25°C added 238.0 gm of thionyl chloride slowly over a period of 4 hours to obtain a second reaction mixture. The so obtained second reaction mixture was equilibrated for 1 hour, and the temperature was raised up to 104 °C (azeotropic reflux) with simultaneous removal of water and by-products to obtain a reaction mass. The azeotropic distillation was continued till there was no more water separation at Dean and stark apparatus. The addition of thionyl chloride and the rise in the temperature leads to the evolution of gases i.e., SO2 and methyl chloride. The SO2 generated was scrubbed with water, and the methyl chloride was passed through the brine cooled condenser and collected as a liquid. The reaction mass was cooled to 65 °C followed by the addition of 1000 ml of methanol and refluxed for 1 hour to obtain a slurry. The slurry was cooled to 20°C followed by filtration to obtain a wet cake and a first filtrate. The so obtained wet cake was washed with 200 ml of methanol and dried to obtain the cartap hydrochloride and a second filtrate. The purity of Cartap hydrochloride was >99.0 % and the yield was 246.0 gram (90.0 m%) gram (Crop I).
The first filtrate and the second filtrate were mixed to obtain a filtrate mixture. The methanol and toluene were recovered from the mixture of first filtrate and second filtrate by distillation till the precipitation of bottom mass to obtain a resultant mixture. The so obtained resultant mixture was mixed with 100 ml of methanol and cooled to 30 °C followed by filtration to obtain cartap hydrochloride (crop II). The cartap hydrochloride (crop II) can be recycled in the next batch.
The purity of Cartap hydrochloride (crop-II) was 88.0 % and the yield was 16.5 gram (6.0 m %).
Example 3:
The reactor was equipped with an overhead stirrer, Dean and Stark system, thermometer, and glass condenser. 300 ml of toluene, 200 ml of methanol, and 100 ml of 30 % w/w HCl were charged into a reactor and heated to 32°C, followed by the addition of 237.5 gram of 90:10 ratios of 1,3-dithiocyanato-2-(dimethylamino) propane hydrochloride salt:1,2-dithiocyanato-3-(dimethylamino)propane hydrochloride salt to obtain a first reaction mixture. The first reaction mixture was cooled to 15°C, maintaining the temperature below 25°C and 238.0 gm of thionyl chloride was slowly added over a period of 4 hours to obtain a second reaction mixture. The so obtained second reaction mixture was equilibrated for 1 hour, and the temperature was raised up to 104 °C (azeotropic reflux) with simultaneous removal of water and by-products to obtain a reaction mass. The azeotropic distillation was continued till there was no more water separation at Dean and stark apparatus. The addition of thionyl chloride and the rise in the temperature leads to the evolution of gases i.e., SO2 and methyl chloride. The SO2 generated was scrubbed with water, and the methyl chloride was passed through the brine cooled condenser and collected as a liquid. The reaction mass was cooled to 65°C followed by the addition of 1000 ml of methanol and refluxed for 1 hour to obtain a slurry. The so obtained slurry was cooled to 20°C followed by filtration to obtain a wet cake and a first filtrate. The so obtained wet cake was washed with 200 ml of methanol and dried to obtain the cartap hydrochloride and a second filtrate. The purity of cartap hydrochloride was >99.0 % and the yield was 205.0 gram (75.0 m%) (Crop I).
The first filtrate and the second filtrate were mixed to obtain a filtrate mixture. The methanol and toluene were recovered from the mixture of first filtrate and second filtrate by distillation till the precipitation of bottom mass to obtain a resultant mixture. The so obtained resultant mixture was mixed with 100 ml of methanol and cooled to 30°C followed by filtration to obtain cartap hydrochloride (crop II). The cartap hydrochloride (crop II) can be recycled in the next batch.
The purity of cartap hydrochloride (crop-II) was 91.0 % and the yield was 11.0 gram (4.0 m %) which was recycled in the next batch.
Example 4:
The reactor was equipped with an overhead stirrer, Dean and Stark system, thermometer, and glass condenser. 750 ml of dichloroethane, 250 ml of methanol, and 100 ml of 30 % w/w HCl were charged into a reactor and heated to 32°C, followed by the addition of 237.5 gram of (98.0 % purity) 1,3-dithiocyanato-2-(dimethylamino) propane hydrochloride salt to obtain a first reaction mixture. The first reaction mixture was cooled to 15°C, maintaining the temperature below 25°C and 238.0 gm of thionyl chloride was slowly added over a period of 4 hours to obtain a second reaction mixture. The so obtained second reaction mixture was equilibrated for 1 hour, and the temperature was raised up to 82 °C (azeotropic reflux) with simultaneous removal of water and by-products to obtain a reaction mass. The azeotropic distillation was continued till there was no more water separation at Dean and stark apparatus. The addition of thionyl chloride and the rise in the temperature leads to the evolution of gases i.e., SO2 and methyl chloride. The SO2 generated was scrubbed with water, and the methyl chloride was passed through brine cooled condenser and collected as a liquid. The reaction mass was cooled to 65°C followed by the addition of 1000 ml of methanol and refluxed for 1 hour to obtain a slurry. The so obtained slurry was cooled to 20°C followed by filtration to obtain a wet cake and first filtrate. The so obtained wet cake was washed with 200 ml of methanol and dried to obtain the cartap hydrochloride and a second filtrate. The purity of Cartap hydrochloride was >99.0 % and the yield was 235.0 gram (86.0 m%) (Crop I).
The first filtrate and the second filtrate were mixed to obtain a filtrate mixture. The methanol and dichloroethane were recovered from the filtrate mixture of the first filtrate and the second filtrate by using distillation till the precipitation of bottom mass to obtain a resultant mixture. The so obtained resultant mixture was mixed with 100 ml of methanol and cooled to 30 °C followed by filtration to obtain cartap hydrochloride (crop II). The cartap hydrochloride (crop II) can be recycled in the next batch.
The purity of cartap hydrochloride (crop-II) was 90.0 % and the yield was 16.4 gram (6.0 m %).
Example 5:
The reactor was equipped with an overhead stirrer, Dean and Stark system, thermometer, and glass condenser. 750 ml of dichloroethane and 350 ml of methanol were charged into the reactor and heated to 32°C, followed by the addition of 237.5 gram of (98.0 % purity) 1, 3-dithiocyanato-2-(dimethylamino) propane hydrochloride salt to obtain a first reaction mixture. The first reaction mixture was cooled to 15°C, maintaining a temperature below 25°C and 476.0 gm of thionyl chloride was slowly added over a period of 4 hours to obtain a second reaction mixture. The so obtained second reaction mixture was equilibrated for 1 hour, and the temperature was raised up to 82°C (azeotropic reflux) with simultaneous removal of water and by-products to obtain a reaction mass. The azeotropic distillation was continued till there was no more water separation at Dean and stark apparatus. The addition of thionyl chloride and the rise in the temperature leads to the evolution of gases i.e. SO2 and methyl chloride. The SO2 generated was scrubbed with water, and the methyl chloride was passed through the brine cooled condenser and collected as a liquid. The reaction mass was cooled to 65°C followed by the addition of 1000 ml of methanol and refluxed for 1 hour to obtain a slurry. The slurry was cooled to 20°C followed by filtration to obtain a wet cake and first filtrate. The so obtained wet cake was washed with 200 ml of methanol and dried to obtain the cartap hydrochloride and second filtrate. The purity of Cartap hydrochloride was >99.0 % and the yield was 224.0 gram (82.0 m%) (Crop I).
The first filtrate and the second filtrate were mixed to obtain a filtrate mixture. The methanol and dichloroethane were recovered from the mixture of the first filtrate and the second filtrate by distillation till the precipitation of bottom mass to obtain a resultant mixture. The so obtained resultant mixture was mixed with 100 ml of methanol and cooled to 30 °C followed by filtration to obtain cartap hydrochloride (crop II). The cartap hydrochloride (crop II) can be recycled in the next batch.
The purity of cartap hydrochloride (crop-II) was 90.0 % and the yield was 11.0 grams (7.0 m %).
Example 6:
The reactor was equipped with an overhead stirrer, Dean and Stark system, thermometer, and glass condenser. 750 ml of dichloroethane, 250 ml of methanol, and 50ml water were charged into the reactor and heated to 32°C, followed by the addition of 237.5 gram of (98.0 % purity) 1,3-dithiocyanato-2-(dimethylamino) propane hydrochloride salt to obtain a first reaction mixture. The first reaction mixture was cooled to 15°C, maintaining a temperature below 25°C and 476.0 gm of thionyl chloride was slowly added over a period of 4 hours to obtain a second reaction mixture. The so obtained second reaction mixture was equilibrated for 1 hour, and the temperature was raised to 82°C (azeotropic reflux) with simultaneous removal of water and by-products to obtain a reaction mass. The azeotropic distillation was continued till there was no more water separation at Dean and stark apparatus. The addition of thionyl chloride and the rise in the temperature leads to the evolution of gases i.e. SO2 and methyl chloride. The SO2 generated was scrubbed with water, and the methyl chloride was passed through the brine cooled condenser and collected as a liquid. The reaction mass was cooled to 65 °C followed by the addition of 1000 ml of methanol and refluxed for 1 hour to obtain a slurry. The slurry was cooled to 20°C followed by filtration to obtain a wet cake and first filtrate. The so obtained wet cake was washed with 200 ml of methanol and dried to obtain the cartap hydrochloride and second filtrate. The purity of Cartap hydrochloride was >99.0 % and the yield was 230.0 gram (84.0 m%).
The first filtrate and the second filtrate were mixed to obtain a filtrate mixture. The methanol and dichloroethane were recovered from the mixture of the first filtrate and the second filtrate by distillation till the precipitation of bottom mass to obtain a resultant mixture. The so obtained resultant mixture was mixed with 100 ml of methanol and cooled to 30°C followed by filtration to obtain cartap hydrochloride (crop II). The cartap hydrochloride (crop II) can be which was recycled in the next batch.
The purity of cartap hydrochloride (crop-II) was 89% and the yield was 19.0 gram (7.0 m%).
Example 7:
The reactor was equipped with an overhead stirrer, Dean and Stark system, thermometer, and glass condenser. 300 ml of toluene, 200 ml of methanol, and 100 ml of 30 % w/w HCl were charged into a reactor and heated to 32°C, followed by adding 201 gm of (98.0 % purity) 1, 3-dithiocyanato-2- (dimethylamino) propane to obtain a first reaction mixture. The first reaction mixture was cooled to 15°C, maintaining the temperature below 25°C, 297.5 gm of thionyl chloride was slowly added over a period of 4 hours to obtain a second reaction mixture. The so obtained second reaction mixture was equilibrated for 1 hour, and the temperature was raised up to 104°C (azeotropic reflux) with simultaneous removal of water and by-products to obtain a reaction mass. The azeotropic distillation was continued till there was no more water separation at Dean and stark apparatus. The addition of thionyl chloride and the rise in the temperature leads to the evolution of gases i.e., SO2 and methyl chloride. The SO2 generated was scrubbed with water, and the methyl chloride was passed through the brine cooled condenser and collected as a liquid. The reaction mass was cooled to 65°C followed by the addition of 1000 ml of methanol and refluxed for 1.0 hour to obtain a slurry. The slurry was cooled to 20°C followed by filtration to obtain a wet cake and a first filtrate. The so obtained wet cake was washed with 200 ml of methanol and dried to obtain the cartap hydrochloride and a second filtrate. The purity of Cartap hydrochloride was >99.0 % and the yield was 241.0 gram (88.0 m %) (Crop I).
The first filtrate and the second filtrate were mixed to obtain a filtrate mixture. The methanol and toluene were recovered from the mixture of the first filtrate and the second filtrate by distillation till the precipitation of bottom mass to obtain a resultant mixture. The so obtained resultant mixture was mixed with 100 ml of methanol and cooled to 30°C followed by filtration to obtain cartap hydrochloride (crop II). The cartap hydrochloride (crop II) can be recycled in the next batch.
The purity of Cartap hydrochloride (crop-II) was 91.0 % and the yield was 8 gram (2.9 m %).

Example 8:
The reactor was equipped with an overhead stirrer, Dean and Stark system, thermometer, and glass condenser. 300 ml of toluene, 200 ml of methanol, and 100 ml of 30 % w/w HCl were charged into a reactor and heated to 32°C, followed by adding 201 gm of gram of 90:10 ratios of 1,3-Dithiocyanato-2-(dimethylamino) propane:1,2-Dithiocyanato-3-(dimethylamino)propane to obtain a first reaction mixture. The first reaction mixture was cooled to 15°C, maintaining the temperature below 25°C added 297.5 gm of thionyl chloride slowly over a period of 4 hours to obtain a second reaction mixture. The so obtained second reaction mixture was equilibrated for 1 hour, and the temperature was raised up to 104 °C (azeotropic reflux) with simultaneous removal of water and by-products to obtain a reaction mass. The azeotropic distillation was continued till there was no more water separation at Dean and stark apparatus. The addition of thionyl chloride and the rise in the temperature leads to the evolution of gases i.e., SO2 and methyl chloride. The SO2 generated was scrubbed with water, and the methyl chloride was passed through the brine cooled condenser and collected as a liquid. The reaction mass was cooled to 65 °C followed by the addition of 1000 ml of methanol and refluxed for 1 hour to obtain a slurry. The slurry was cooled to 20°C followed by filtration to obtain a wet cake and a first filtrate. The so obtained wet cake was washed with 200 ml of methanol and dried to obtain the cartap hydrochloride and a second filtrate. The purity of Cartap hydrochloride was >99.0 % and the yield was 205.0 gram (75.0 m%) gram (Crop I).
The first filtrate and the second filtrate were mixed to obtain a filtrate mixture. The methanol and toluene were recovered from the mixture of first filtrate and second filtrate by distillation till the precipitation of bottom mass to obtain a resultant mixture. The so obtained resultant mixture was mixed with 100 ml of methanol and cooled to 30 °C followed by filtration to obtain cartap hydrochloride (crop II). The cartap hydrochloride (crop II) can be recycled in the next batch.
The purity of Cartap hydrochloride (crop-II) was 91.0 % and the yield was 8 gram (2.9 m %).
It is evident from the above examples that the process of the present disclosure doesn’t use dry HCl, thus avoiding expensive infrastructure requirements for performing the reaction. Further, the optimized process conditions ensure the obtained product with high purity (>99%) irrespective of the raw material quality (90:10 reactant isomer ratio).
TECHNICAL ADVANCEMENTS
The present disclosure described hereinabove has several technical advantages including, but not limited to, the realization of a process for the preparation of cartap hydrochloride, that:
? is simple, efficient, and economical;
? provides cartap hydrochloride in high yield along with high purity;
? is environment friendly as solvents/ by-products are recycled;
? employs reagents which can be handled easily; and
? avoids the use of dry HCl gas, thus avoiding additional infrastructure requirements.
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.
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.
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.