DESC:FIELD
The present disclosure relates to a process for the preparation of 1-methylhexyl(5-chloroquinolin-8-yloxy)acetate.
BACKGROUND
Safeners are molecules used in combination with herbicides to protect a crop from incidental damage caused by herbicides. Safeners improve selectivity of a herbicide between the crops and the weed species being targeted by the herbicide.
1-Methylhexyl(5-chloroquinolin-8-yloxy)acetate is used as a safener, and is commonly known as cloquintocet mexyl. 1-Methylhexyl(5-chloroquinolin-8-yloxy)acetate improves the tolerance of the crop to the effect of the herbicide and selectively controls annual grasses in crops. It degrades rapidly and binds strongly to the soil, hence has a low leaching potential. 1-Methylhexyl(5-chloroquinolin-8-yloxy)acetate also facilitates degradation of the herbicide in the soil.
Conventional processes for the preparation of 1-methylhexyl(5-chloroquinolin-8-yloxy)acetate are associated with drawbacks such as use of mixed reaction solvents, higher reaction temperature, complex reaction procedures, and a low purity product.
There is, therefore, felt a need to provide a simple, economical, and environmentally-friendly process for the preparation of 1-methylhexyl(5-chloroquinolin-8-yloxy)acetate with high purity.
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 1-methylhexyl(5-chloroquinolin-8-yloxy)acetate.
Yet another object of the present disclosure is to provide a simple, economical, and environmentally-friendly process for the preparation of 1-methylhexyl(5-chloroquinolin-8-yloxy)acetate.
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 provides a process for the preparation of 1-methylhexyl(5-chloroquinolin-8-yloxy)acetate.
5-Chloro-8-hydroxyquinoline, at least one base, and at least one activator are mixed with at least one first fluid medium to obtain a first reaction mixture. The first reaction mixture is heated at a temperature in the range of 60°C to 130°C, while removing water formed during the reaction, as an azeotrope with the first fluid medium to obtain a first resultant mixture and a distillate comprising water and the first fluid medium. 2-Heptylchloroacetate is added slowly to the first resultant mixture to obtain a second reaction mixture. The second reaction mixture is heated at a temperature in the range of 60°C to 130°C for a period of time in the range of 10 hours to 15 hours to obtain a product mixture comprising 1-methylhexyl(5-chloroquinolin-8-yloxy)acetate. At least one second fluid medium is added to the product mixture and 1-methylhexyl(5-chloroquinolin-8-yloxy)acetate is separated therefrom by crystallization to obtain crystals of 1-methylhexyl(5-chloroquinolin-8-yloxy)acetate having purity in the range of 98% to 99.9%.
The first fluid medium and the second fluid medium are independently selected from the group consisting of octane, n-heptane, and hexane.
The process of the present disclosure optionally comprises separation of the first fluid medium from the distillate and reusing it as the second fluid medium.
The base is selected from the group consisting of sodium carbonate, sodium bicarbonate, cesium carbonate, and potassium carbonate. The mole ratio of 5-chloro-8-hydroxyquinoline and the base is in the range of 1:0.8 to 1:5.
The activator is selected from the group consisting of potassium iodide and sodium iodide. The mole ratio of 5-chloro-8-hydroxyquinoline and the activator is in the range of 100:1 to 10:1.
The addition of 2-heptylchloroacetate to the first resultant mixture is carried out over a period of time in the range of 1 hour to 5 hours.
The mole ratio of 5-chloro-8-hydroxyquinoline and 2-heptylchloroacetate is in the range of 1:0.8 to 1:5.
DETAILED DESCRIPTION
1-Methylhexyl(5-chloroquinolin-8-yloxy)acetate is used inter alia as a safener in combination with different herbicides. 1-Methylhexyl(5-chloroquinolin-8-yloxy)acetate reduces the harmful effects of herbicides on crops, and also increases selectivity of the herbicides.
The molecular structure for 1-methylhexyl(5-chloroquinolin-8-yloxy)acetate is represented as follow:

Conventional processes for the preparation of 1-methylhexyl(5-chloroquinolin-8-yloxy)acetate (I) are associated with drawbacks such as use of complex reaction procedures, and a low purity product. The present disclosure envisages a simple process that provides I in high yield.
The present disclosure provides a simple, economical and eco-friendly process for the preparation of 1-methylhexyl(5-chloroquinolin-8-yloxy)acetate from 5-chloro-8-hydroxyquinoline.
The scheme for the preparation of 1-methylhexyl(5-chloroquinolin-8-yloxy)acetate (I), in accordance with the process of the present disclosure, is shown in scheme I:
Scheme I: Preparation of 1-methylhexyl(5-chloroquinolin-8-yloxy)acetate

The process of the preparation of 1-methylhexyl(5-chloroquinolin-8-yloxy)acetate, in accordance with the process of the present disclosure involves the following steps:
In the process of the present disclosure, 5-chloro-8-hydroxyquinoline (II), at least one base, and at least one activator are mixed with the first fluid medium to obtain a first reaction mixture. The first reaction mixture is heated at a temperature in the range of 60°C to 130°C, while removing water formed during the reaction, as an azeotrope with the first fluid medium to obtain a first resultant mixture and a distillate comprising water and the first fluid medium.
Further, 2-heptyl chloroacetate (III) is slowly added to the first resultant mixture to obtain a second reaction mixture. The second reaction mixture is heated at a temperature in the range of 60°C to 130°C for a period of time in the range of 10 hours to 15 hours to obtain a product mixture comprising 1-methylhexyl(5-chloroquinolin-8-yloxy)acetate. At least one second fluid medium is added to the product mixture and 1-methylhexyl(5-chloroquinolin-8-yloxy)acetate is separated therefrom by crystallization to obtain crystals of 1-methylhexyl(5-chloroquinolin-8-yloxy)acetate having purity in the range of 98% to 99.9%.
In accordance with the embodiments of the present disclosure, the step of separating 1-methylhexyl(5-chloroquinolin-8-yloxy)acetate from the product mixture by crystallization involves the following steps:
The second fluid medium is added to the product mixture and heated at 60°C to 130°C for 1 hour to 5 hours. The hot product mixture is then filtered and the residue obtained is washed with the second fluid medium having a temperature in the range of 50°C to 100°C. The combined hot filtrate is allowed to cool to obtain the crystals of 1-methylhexyl(5-chloroquinolin-8-yloxy)acetate and a liquid portion. The crystals of 1-methylhexyl(5-chloroquinolin-8-yloxy)acetate are separated by filtration and washed with the second fluid medium having a temperature in the range of 10°C to 30°C to obtain 1-methylhexyl(5-chloroquinolin-8-yloxy)acetate having purity in the range of 98% to 99.9%.
In accordance with the embodiments of the present disclosure, the first fluid medium is separated from the distillate. Optionally, the separated first fluid medium is used as the second fluid medium.
In accordance with the embodiments of the present disclosure, the second fluid medium used in the step of crystallization can be recovered and re-used.
In accordance with the embodiments of the present disclosure, the first fluid medium and the second fluid medium are independently selected from the group consisting of hexane, heptane, and octane. In an exemplary embodiment of the present disclosure, the first fluid medium and the second fluid medium are n-heptane.
In accordance with the embodiments of the present disclosure, the addition of 2-heptylchloroacetate to the first resultant mixture is carried out over a period of time in the range of 1 hour to 5 hours.
In accordance with the embodiments of the present disclosure, the mole ratio of 5-chloro-8-hydroxyquinoline and 2-heptylchloroacetate is in the range of 1:0.8 to 1:5. In an exemplary embodiment of the present disclosure, the mole ratio of 5-chloro-8-hydroxyquinoline and 2-heptylchloroacetate is 1:1.
In accordance with the embodiments of the present disclosure, the base is selected from the group consisting of sodium carbonate, sodium bicarbonate, cesium carbonate, and potassium carbonate. In an exemplary embodiment of the present disclosure, the base is sodium carbonate.
In accordance with the embodiments of the present disclosure, the mole ratio of 5-chloro-8-hydroxyquinoline and the base is in the range of 1:0.8 to 1:5. In an exemplary embodiment of the present disclosure, the mole ratio of 5-chloro-8-hydroxyquinoline and the base is 1:1.2.
In accordance with the embodiments of the present disclosure, the activator is selected from the group consisting of potassium iodide and sodium iodide. In an exemplary embodiment of the present disclosure, the activator is potassium iodide.
In accordance with the embodiments of the present disclosure, the mole ratio of 5-chloro-8-hydroxyquinoline and the activator is in the range of 100:1 to 10:1. In an exemplary embodiment of the present disclosure, the mole ratio of 5-chloro-8-hydroxyquinoline and the activator is 100:3.
The present disclosure provides a process for the preparation of 1-methylhexyl(5-chloroquinolin-8-yloxy)acetate with a yield in the range of 70% to 80%.
The process of the present disclosure is simple. Further, the process of the present disclosure uses readily available materials. Furthermore, the fluid medium used in the process is re-used. Therefore, the process of the present disclosure is simple, economical and environmentally-friendly.
The present disclosure is further described in light of the following experiments which are set forth for illustration purpose only and not to be construed for limiting the scope of the disclosure.
EXPERIMENTS
Experiment-I: Preparation of 1-methylhexyl(5-chloroquinolin-8-yloxy)acetate (I)
5-Chloro-8-hydroxyquinoline (650 kg), sodium carbonate (462 kg), and potassium iodide (20 kg) were mixed with n-heptane (2800 lit) under continuous stirring to obtain a first reaction mixture and the so obtained first reaction mixture was heated at 94°C. Water formed during the reaction was removed as an azeotrope with n-heptane to obtain a first resultant mixture (2850 kg). During azeotropic distillation, a mixture of n-heptane (600 lit) and water (25 lit) was distilled out.
2-Heptylchloroacetate (731 kg) was slowly added to the first resultant mixture over 1 hour to obtain a second reaction mixture. The second reaction mixture was heated at 103°C for 12 hours to obtain a product mixture comprising 1-methylhexyl(5-chloroquinolin-8-yloxy)acetate. The progress of the reaction was monitored by thin layer chromatography (TLC).
After completion of the reaction, n-heptane (600 lit, recovered from the distillate) was added to the product mixture followed by heating at 84°C for 1 hour. The hot product mixture was filtered and the residue obtained was washed with n-heptane having temperature of 80°C. The combined hot filtrate was allowed to cool to obtain the crystals of 1-methylhexyl(5-chloroquinolin-8-yloxy)acetate (I). The crystals of 1-methylhexyl(5-chloroquinolin-8-yloxy)acetate were separated by filtration and washed with n-heptane having temperature of 20°C to obtain 1-methylhexyl(5-chloroquinolin-8-yloxy)acetate (I) (910 kg) having a purity of 99.2%.
Two experiments were carried out using the same experimental procedure as described in Experiment I.
Experiment II was carried out using reaction conditions same as in Experiment I except the use of mixed bases i.e. mixture of Na2CO3 and K2CO3 in the ratio of 1:1 instead of use of single base Na2CO3.
Experiment III was carried out using reaction conditions same as in Experiment I except the following:
• The mole ratio of 5-chloro-8-hydroxyquinoline and 2-heptylchloroacetate was 1:1.1 instead of 1:1;
• After addition of 2-heptylchloroacetate, the reaction mixture was heated for 9 hours instead of 12 hours.
The details including the results of the experiments I to III are summarized in table I.

Table 1:
Expt. Solvent Base Activator 2-heptyl chloro-acetate Yield Purity
I n-heptane 2800 lit Na2CO3 462 kg KI 20 kg 731 kg 910 kg 99.2%
II n-heptane 2800 lit Na2CO3 231 kg KI 20 kg 731 kg 890 kg 99.2%
K2CO3 301 kg
III n-heptane 2800 lit Na2CO3 462 kg KI 20 kg 804 kg 820 kg 99%

Thus, it was observed from Experiments I and II that, the change in base from sodium carbonate to a 1:1 mixture of Na2CO3 and K2CO3 led to substantially same yield.
On comparison of yields of experiments I and III, it was evident that excess use of 2-heptylchloroacetate led to low yield of I. The low yields can be attributed to solubility of I in 2-heptylchloroacetate due to which I goes in filtrate with excess 2-heptylchloroacetate.

TECHNICAL ADVANCEMENTS
The present disclosure described herein above has several technical advantages including, but not limited to, the realization of a process for preparation of 1-methylhexyl(5-chloroquinolin-8-yloxy)acetate, that is:
- simple;
- economical; and
- eco-friendly.
Throughout this specification the word “comprise”, or variations such as “comprises” or “comprising”, will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.
The use of the expression “at least” or “at least one” suggests the use of one or more elements or ingredients or quantities, as the use may be in the embodiment of the 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.
While considerable emphasis has been placed herein on the specific features of the preferred embodiment, it will be appreciated that many additional features can be added and that many changes can be made in the preferred embodiment without departing from the principles of the disclosure. These and other changes in the preferred embodiment of the disclosure will be apparent to those skilled in the art from the disclosure herein, whereby it is to be distinctly understood that the foregoing descriptive matter is to be interpreted merely as illustrative of the disclosure and not as a limitation.
,CLAIMS:1. A process of preparing 1-methylhexyl(5-chloroquinolin-8-yloxy)acetate from 5-chloro-8-hydroxyquinoline, said process comprising the following steps:
a. mixing 5-chloro-8-hydroxyquinoline, at least one base, and at least one activator with at least one first fluid medium to obtain a first reaction mixture and heating said first reaction mixture at a temperature in the range of 60°C to 130°C, while removing formed water from said first reaction mixture as an azeotrope with said first fluid medium to obtain a first resultant mixture and a distillate comprising water and said first fluid medium;
b. adding 2-heptylchloroacetate slowly to said first resultant mixture to obtain a second reaction mixture, followed by heating said second reaction mixture at a temperature in the range of 60°C to 130°C for a period of time in the range of 10 hours to 15 hours to obtain a product mixture comprising 1-methylhexyl(5-chloroquinolin-8-yloxy)acetate; and
c. adding at least one second fluid medium to said product mixture and separating 1-methylhexyl(5-chloroquinolin-8-yloxy)acetate therefrom by crystallization to obtain crystals of 1-methylhexyl(5-chloroquinolin-8-yloxy)acetate having purity in the range of 98% to 99.9%.
2. The process as claimed in claim 1, further comprises a step of separation of said first fluid medium from said distillate obtained in step (a), and using separated first fluid medium as the second fluid medium in step (c).
3. The process as claimed in claim 1, wherein said at least one first fluid medium and said at least one second fluid medium are independently selected from the group consisting of octane, n-heptane, and hexane.
4. The process as claimed in claim 1, wherein said at least one base is selected from the group consisting of sodium carbonate, sodium bicarbonate, cesium carbonate, and potassium carbonate.
5. The process as claimed in claim 1, wherein the mole ratio of 5-chloro-8-hydroxyquinoline and said base is in the range of 1:0.8 to 1:5.
6. The process as claimed in claim 1, wherein said at least one activator is selected from the group consisting of potassium iodide and sodium iodide.
7. The process as claimed in claim 1, wherein the mole ratio of 5-chloro-8-hydroxyquinoline and said activator is in the range of 100:1 to 10:1.
8. The process as claimed in claim 1, wherein the mole ratio of 5-chloro-8-hydroxyquinoline and 2-heptyl chloroacetate is in the range of 1:0.8 to 1:5.
9. The process as claimed in claim 1, wherein the addition of 2-heptylchloroacetate to said first resultant mixture is carried out over a period of time in the range of 1 hour to 5 hours.