DESC:FIELD
The present disclosure relates to a process for chlorination of 7-methylisatin.
BACKGROUND
The background information herein below relates to the present disclosure but is not necessarily prior art.
Isatin derivatives are useful in the synthesis of oxindoles, 4-carboxyquinolines, and other biologically-active substances such as Chlorantraniliprole. Chlorantraniliprole is an insecticide of the ryanoid class. Ryanodine is a naturally occurring insecticide isolated from Ryania speciosa.
7-methylisatin is a heterocyclic compound and is also known as indanedione or indole quinone. The structure of 7-methylisatin is represented as given:

Further, 5-chloro-7-methylisatin shows a wide range of biological and pharmacological activity, including anti-bacterial, anti-fungal and anti-HIV properties. Conventionally, the process of chlorination of 7-methylisatin uses trichloro-isocyanuric acid (TICA) and sulfuryl chloride as a chlorinating agent and acetic acid as a solvent to produce 5-chloro-7-methylisatin. The reactants TICA, sulfuryl chloride and acetic acid are expensive and hence the process is uneconomical.
Therefore, there is felt a need to provide a process for chlorination of 7-methylisatin which mitigates the drawbacks mentioned herein above.

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 chlorination of 7-methylisatin.
Still another object of the present disclosure is to provide a process for chlorination of 7-methylisatin that uses inexpensive reagents and hence is economical.
Yet another object of the present disclosure is to provide a simple, efficient and environmental friendly process for chlorination of 7-methylisatin.
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 chlorination of 7-methylisatin. The process comprises mixing 7-methylisatin in a predetermined amount of hydrochloric acid having a predetermined normality under stirring to obtain a slurry. Chlorine gas is passed through the slurry at a pre-determined temperature and for a pre-determined time period to obtain a product mixture comprising 5-chloro-7-methylisatin. 5-chloro-7-methylisatin is separated from the product mixture to obtain 5-chloro-7-methylisatin with a yield in the range of 80% to 95% and having a purity in the range of 90% to 98%.
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.
Isatin derivatives are also useful in the synthesis of oxindoles, 4-carboxyquinolines, and other biologically-active substances such as Chlorantraniliprole. Chlorantraniliprole is an insecticide of the ryanoid class. Ryanodine is a naturally occurring insecticide isolated from Ryania speciosa.
7-methylisatin is a heterocyclic compound and is also known as indanedione or indole quinone. The structure of 7-methylisatin is represented as given:

5-chloro-7-methylisatin shows a wide range of biological and pharmacological activity, including anti-bacterial, anti-fungal and anti-HIV properties. Conventionally, the process of chlorination of 7-methylisatin uses trichloro-isocyanuric acid (TICA) and sulfuryl chloride as a chlorinating agent and acetic acid as a solvent to produce 5-chloro-7-methylisatin. The reactants TICA, sulfuryl chloride and acetic acid are expensive and hence the process turns out to be uneconomical.
The present disclosure provides a process for chlorination of 7-methylisatin.
The process comprises the following steps:
i. mixing 7-methylisatin in a predetermined amount of hydrochloric acid having a predetermined normality under stirring to obtain a slurry;
ii. passing chlorine gas through the slurry at a pre-determined temperature and for a pre-determined time period to obtain a product mixture comprising 5-chloro-7-methylisatin; and
iii. separating 5-chloro-7-methylisatin from the product mixture to obtain 5-chloro-7-methylisatin with a yield in the range of 80% to 95% and having a purity in the range of 90% to 98%.
A schematic representation of the process of chlorination of 7-methylisatin is represented as below:

In accordance with an embodiment of the present disclosure, the predetermined amount of the hydrochloric acid is in the range of 500 ml/mole to 750 ml/mole. In an exemplary embodiment, the predetermined amount of the hydrochloric acid is 600 ml/mole.
In accordance with an embodiment of the present disclosure, the normality of hydrochloric acid is in the range of 2N to 10N. In an exemplary embodiment, the normality of hydrochloric acid is 2N. In another exemplary embodiment, the normality of hydrochloric acid is 8N.
In accordance with an embodiment of the present disclosure, a molar ratio of 7-methylisatin to the hydrochloric acid is in the range of 1:1.2 to 1:5.
In accordance with the present disclosure, a molar ratio of 7-methylisatin to the chlorine gas is in the range of 1:1.5 to 1:2. In an embodiment of the present disclosure, the molar ratio of 7-methylisatin to the chlorine gas is in the range of 1:1.57 to 1:1.73. In an exemplary embodiment, the molar ratio of 7-methylisatin to the chlorine gas is 1:1.57. In an exemplary embodiment, the molar ratio of 7-methylisatin to the chlorine gas is 1:1.73.
In accordance with the present disclosure, the predetermined temperature is in the range of 20oC to 40oC. In an exemplary embodiment, the predetermined temperature is 30 oC.
In accordance with an embodiment of the present disclosure, the predetermined time period is in the range of 2 hours to 6 hours. In an exemplary embodiment, the predetermined time period is 4 hours.
The process of the present disclosure is simple. The process uses inexpensive reagents and hence the process is economical. During the process of chlorination of 7-methylisatin, neither any effluent nor any residue is generated and hence the process of the present disclosure is environment 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
Process for chlorination of 7-methylisatin to obtain 5-chloro-7-methylisatin in accordance with the present disclosure
Experiment 1:
300 ml of 2N HCl was taken in a reactor and 86.4 gms of 7-methylisatin (0.5 mole) was added to it under stirring to obtain an orange colored slurry. Chlorine gas was passed through the slurry at 25-30 oC and the reaction progress was monitored by using HPLC. The chlorine gas was passed for a time period of 4 hours (total 1.57 mole/mole) to obtain a product mixture. The product mixture was analyzed. The so obtained product mixture comprises 5-chloro-7-methylisatin and un-reacted 7-methylisatin.
The product mixture was filtered to obtain a cake. The cake was washed with water to obtain a wet cake. The wet cake was dried to obtain 5-chloro-7-methylisatin having a purity of 95% and a yield on purity of 86%.
Experiment 2:
300 ml of 6N HCl was taken in a reactor and 86.4 gms of 7-methylisatin (0.5 mole) was added to it under stirring to obtain an orange colored slurry. Chlorine gas was passed through the slurry at 25-30oC. The progress of the reaction was monitored by using HPLC. The chlorine gas was passed for a time period of 4 hrs (total 1.57 mole/mole) to obtain a product mixture. The product mixture was analyzed. The so obtained product mixture comprises 5-chloro-7-methylisatin and unreacted 7-methylisatin.
The product mixture was filtered to obtain a cake. The cake was washed with water to obtain a wet cake. The wet cake was dried to obtain 5-chloro-7-methylisatin having a purity of 95% and a yield on purity of 86%.
Experiment 3:
300 ml of 8N HCl was taken in a reactor and 86.4 gms. of 7-methylisatin (0.5 mole) was added to it under stirring to obtain an orange coloured slurry. Chlorine gas was passed through the slurry at 25-30 oC. The progress of the reaction was monitored by using HPLC. The chlorine gas was passed for a time period of 4 hrs (total 1.57 mole/mole) to obtain a product mixture. The product mixture was analyzed. The so obtained product mixture comprises 5-chloro-7-methylisatin and unreacted 7-methylisatin.
The product mixture was filtered to obtain a cake. The cake was washed with water to obtain a wet cake. The wet cake was dried to obtain 5-chloro-7-methylisatin having a purity of 96.50 % and a yield on purity of 91%.
Experiment 4:
450 ml of water was taken in a reactor and 127 gms. of 7-methylisatin (0.75 mole) was added to it under stirring to obtain an orange coloured slurry. Chlorine gas was passed through the slurry at 25-30 oC. The progress of the reaction was monitored by using HPLC. The chlorine gas was passed for a time period of 4 hrs (total 1.73 mole/mole) to obtain a product mixture. The product mixture was analyzed. The so obtained product mixture comprises 5-chloro-7-methylisatin and unreacted 7-methylisatin.
The product mixture was filtered to obtain a cake. The cake was washed with water to obtain a wet cake. The wet cake was dried to obtain 5-chloro-7-methylisatin having dry weight of 125 gms and a purity of 83.6 %.
TECHNICAL ADVANCEMENTS
The present disclosure described herein above has several technical advantages including, but not limited to, the realization and a process for the chlorination of 7-methylisatin, that;
- is simple and economical;
- provides a comparatively higher purity and high yield of chlorinated product;
- generates no effluent or residue during the process, hence the process is environment friendly; and
- uses inexpensive reagents and hence the process is economical.
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 chlorination of 7-methylisatin, said process comprising the following steps:
i. mixing 7-methylisatin in a predetermined amount of hydrochloric acid having a predetermined normality under stirring to obtain a slurry;
ii. passing chlorine gas through said slurry at a pre-determined temperature and for a pre-determined time period to obtain a product mixture comprising 5-chloro-7-methylisatin; and
iii. separating 5-chloro-7-methylisatin from said product mixture to obtain 5-chloro-7-methylisatin with a yield in the range of 80% to 95% and having a purity in the range of 90% to 98%.
2. The process as claimed in claim 1, wherein said predetermined amount of said hydrochloric acid is in the range of 500 ml/mole to 750 ml/mole.
3. The process as claimed in claim 1, wherein said predetermined normality of said hydrochloric acid is in the range of 2N to 10N.
4. The process as claimed in claim 3, wherein said predetermined normality of said hydrochloric acid is in the range of 2N to 8N.
5. The process as claimed in claim 1, wherein a molar ratio of 7-methylisatin to said hydrochloric acid is in the range of 1:1.2 to 1:5.
6. The process as claimed in claim 1, wherein a molar ratio of 7-methylisatin to said chlorine gas is in the range of 1:1.5 to 1:2.
7. The process as claimed in claim 6, wherein said molar ratio of 7-methylisatin to said chlorine gas is in the range of 1:1.57 to 1:1.73.
8. The process as claimed in claim 1, wherein said predetermined temperature is in the range of 20oC to 40oC.
9. The process as claimed in claim 1, wherein said predetermined time period is in the range of 2 hours to 6 hours.
Dated this 21st day of October, 2021

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

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