DESC:FIELD
The present disclosure relates to a process for the preparation of xanthone compounds.
BACKGROUND
The background information herein below relates to the present disclosure but is not necessarily prior art.
Xanthone compounds such as 1-Cyano-6-(methylsulfonyl)-9H-Xanthen-9-one, 1-Cyano-6-(methylsulfonyl)-7-nitro-9H-Xanthen-9-one and the like are obtained during the preparation of the triketone class of herbicides such as Mesotrione i.e., (2-[4-(methanesulfonyl)-2-nitrobenzoyl]cyclohexane-1,3-dione). Mesotrione is a well-known herbicide used in agrochemical industries. Mesotrione inhibits 4-Hydroxyphenylpyruvate dioxygenase (HPPD).
During the registration of pesticides, all the ingredients in the pesticide are required to be provided to the registration authorities. The ingredients may contain impurities (that are produced along with the pesticides) for which impurity conditions including impurity names, contents, structures, necessary qualitative spectrograms and the like are required to be provided during the registration. Therefore, extensive studies on the impurity components, such as the structure and properties are necessary to be carried out. Because the content of xanthone compounds in the production process of mesotrione is low, the extraction of the xanthone compounds is not feasible, and therefore the xanthone compounds are required to be synthesized.
Therefore, there is felt a need to provide a process for the preparation of xanthone compounds.
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 xanthone compounds.
Yet another object of the present disclosure is to provide a process for the preparation of comparatively high purity xanthone compounds.
Another object of the present disclosure is to provide a simple, efficient and environmental friendly process for the preparation of xanthone compounds.
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 xanthone compounds of Formula (I),

(Formula I)
wherein R is H, or NO2.
The process comprising chlorinating 4-(Methylsulfonyl)toluene by using at least one chlorinating agent and at least one mineral acid at a first predetermined temperature for a first predetermined time period to obtain 2-chloro-4-methylsulfonyl toluene. The so obtained 2-chloro-4-methylsulfonyl toluene is oxidized by using at least one oxidizing agent in a first fluid medium in the presence of at least one first catalyst at a second predetermined temperature for a second predetermined time period followed by heating at a third predetermined temperature to obtain 2-chloro-4-methylsulfonyl benzoic acid. Optionally 2-chloro-4-methylsulfonyl benzoic acid is nitrated by using at least one nitrating agent at a fourth predetermined temperature for a third predetermined time period to obtain 4-methylsulfonyl-2-chloro-5 nitro-benzoic acid. 2-chloro-4-methylsulfonyl benzoic acid or 4-methylsulfonyl-2-chloro-5 nitro- benzoic acid is condensed with m-cyano phenol by using at least one inorganic base in a second fluid medium in the presence of at least one second catalyst at a fifth predetermined temperature for a fourth predetermined time period to obtain ether of 2-chloro-4-methylsulfonyl benzoic acid or ether of 4-methylsulfonyl-2-chloro-5 nitro- benzoic acid. The ether of 2-chloro-4-methylsulfonyl benzoic acid or the ether of 4-methylsulfonyl-2-chloro-5 nitro-benzoic acid is cyclized by using at least one cyclizing agent at a sixth predetermined temperature for a fifth predetermined time period to obtain xanthone compounds of Formula (I).
DETAILED DESCRIPTION
The present disclosure relates to a process for the preparation of xanthone compounds.
Embodiments, of the present disclosure, will now be described herein. 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.
Xanthone compounds such as 1-Cyano-6-(methylsulfonyl)-9H-Xanthen-9-one, 1-Cyano-6-(methylsulfonyl)-7-nitro-9H-Xanthen-9-one and the like are obtained during the preparation of the triketone class of herbicides such as Mesotrione i.e., (2-[4-(methanesulfonyl)-2-nitrobenzoyl]cyclohexane-1,3-dione). Mesotrione is a well-known herbicide used in agrochemical industries. Mesotrione inhibits 4-Hydroxyphenylpyruvate dioxygenase (HPPD).
During the registration of pesticides, all the ingredients in the pesticide are required to be provided to the registration authorities. The ingredients may contain impurities (that are produced along with the pesticides) for which impurity conditions including impurity names, contents, structures, necessary qualitative spectrograms and the like are required to be provided during the registration. Therefore, extensive studies on the impurity components, such as the structure and properties are necessary to be carried out. Because the content of xanthone compounds in the production process of mesotrione is low, the extraction of the xanthone compounds is not feasible, and therefore the xanthone compounds are required to be synthesized.
The present disclosure provides a simple, environment friendly and economical process for the preparation of xanthone compounds of Formula (I).
The process for preparing xanthone compounds of Formula (I) comprising the following steps:

(Formula I)
wherein R is H, or NO2.
(i) chlorinating 4-(Methylsulfonyl)toluene by using at least one chlorinating agent and at least one mineral acid at a first predetermined temperature for a first predetermined time period to obtain 2-chloro-4-methylsulfonyl toluene;
(ii) oxidizing 2-chloro-4-methylsulfonyl toluene by using at least one oxidizing agent in a first fluid medium in the presence of at least one first catalyst at a second predetermined temperature for a second predetermined time period followed by heating the reactor at a third predetermined temperature to obtain 2-chloro-4-methylsulfonyl benzoic acid;
(iii) optionally nitrating 2-Chloro-4-methylsulfonyl benzoic acid by using at least one nitrating agent at a fourth predetermined temperature for a third predetermined time period to obtain 4-methylsulfonyl-2-chloro-5 nitro- benzoic acid;
(iv) condensing 2-chloro-4-methylsulfonyl benzoic acid obtained in step (ii) or 4-methylsulfonyl-2-chloro-5 nitro- benzoic acid obtained in step (iii) with m-cyano phenol by using at least one inorganic base in a second fluid medium in the presence of at least one second catalyst at a fifth predetermined temperature for a fourth predetermined time period to obtain ether of 2-chloro-4-methylsulfonyl benzoic acid or ether of 4-methylsulfonyl-2-chloro-5 nitro- benzoic acid; and
(v) cyclizing ether of 2-chloro-4-methylsulfonyl benzoic acid or ether of 4-methylsulfonyl-2-chloro-5 nitro- benzoic acid by using at least one cyclizing agent at a sixth predetermined temperature for a fifth predetermined time period to obtain xanthone compounds of Formula (I).
The process of the present disclosure is described in detail as:
In a first step, 4-(Methylsulfonyl) toluene (II) is chlorinated by using at least one chlorinating agent and at least one mineral acid at a first predetermined temperature for a first predetermined time period to obtain 2-chloro-4-methylsulfonyl toluene (III).
In accordance with the present disclosure, the chlorinating agent is at least one selected from the group consisting of chlorine gas, N-Chloro succinimide, and Sulfuryl chloride (SO2Cl2). In an exemplary embodiment of the present disclosure, the chlorinating agent is chlorine gas.
In accordance with the present disclosure, the mineral acid is at least one selected from the group consisting of sulphuric acid, hydrochloric acid, and nitric acid. In an exemplary embodiment of the present disclosure, the mineral acid is sulphuric acid (H2SO4).
In accordance with the present disclosure, the first predetermined temperature is in the range of 75°C to 95°C. In an exemplary embodiment of the present disclosure, the first predetermined temperature is 85°C.
In accordance with the present disclosure, the first predetermined time period is in the range of 8 hours to 12 hours. In an exemplary embodiment of the present disclosure, the first predetermined time period is 10 hours.
The schematic representation of the chlorination of 4-(Methylsulfonyl) toluene (II) to obtain 2-chloro-4-methanesulfonyl toluene (III) in accordance with step (i) is given below as Scheme 1A, as an exemplary embodiment:

Scheme 1A
In a second step, 2-chloro-4-methylsulfonyl toluene (III) is oxidized by using at least one oxidizing agent in a first fluid medium in the presence of at least one first catalyst at a second predetermined temperature for a second predetermined time period followed by heating at a third predetermined temperature to obtain 2-chloro-4-methylsulfonyl benzoic acid (IV);
In accordance with the present disclosure, the oxidizing agent is at least one selected from oxygen and air. In an exemplary embodiment of the present
disclosure, the oxidizing agent is oxygen.
The first fluid medium is at least one selected from the group consisting of acetic acid, formic acid and oxalic acid. In an exemplary embodiment of the present
disclosure, the first fluid medium is acetic acid.
In accordance with the present disclosure, the first catalyst is at least one selected from the group consisting of cobalt acetate (Co(OAC)2.4H2O), manganese acetate (Mn(OAc)2), sodium bromide (NaBr). In an exemplary embodiment of the present disclosure, the first catalyst is a combination of cobalt acetate (Co(OAC)2.4H2O), manganese acetate (Mn(OAc)2), and sodium bromide (NaBr).
In accordance with the present disclosure, the second predetermined temperature is in the range of 130 °C to 170 °C. In an exemplary embodiment of the present disclosure, the second predetermined temperature is 150 °C.
In accordance with 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 accordance with the present disclosure, the third predetermined temperature is in the range of 150 °C to 170 °C. In an exemplary embodiment of the present disclosure, the third predetermined temperature is 160 °C.
In accordance with an embodiment of the present disclosure, the oxygen is passed to a reactor having a pressure in the range of 1 kg/cm2 to 10 kg/cm2, and the reactor is heated to a temperature in the range of 130 °C to 170 °C for 30 minutes to 120 minutes. Further, the oxygen was continuously passed into the reaction mixture in the reactor to attain a pressure in the range of 10 kg/cm2 to 30 kg/cm2 and the reactor is heated to a temperature in the range of 150 oC to 170°C till no more consumption of oxygen is required.
In an exemplary embodiment of the present disclosure, the oxygen is passed to a reactor having a pressure of 5 kg/cm2, and the reactor is heated to a temperature of 150 °C for 60 minutes. Further, the oxygen was continuously passed into the reaction mixture in the reactor to attain a pressure of 20 kg/cm2 and the reactor is heated to a temperature of 160°C till no more consumption of oxygen is required.
The schematic representation of the oxidation of 2-Chloro-4-methylsulfonyl toluene (III) to obtain 2-Chloro-4-methylsulfonyl benzoic acid (IV) in accordance with step (ii) is given below as Scheme 1B:

Scheme 1B
The so obtained 2-Chloro-4-methylsulfonyl benzoic acid (IV) is optionally nitrated by using at least one nitrating agent at a fourth predetermined temperature for a third predetermined time period to obtain 4-methylsulfonyl-2-chloro-5 nitro- benzoic acid (V).
In accordance with the present disclosure, the nitrating agent is selected from HNO3, H2SO4 and oleum. In an exemplary embodiment, the nitrating agent is a mixture of HNO3 and H2SO4. In another exemplary embodiment, the nitrating agent is the mix acid.
In accordance with the present disclosure, the mix acid is prepared by mixing 100 g of 24% oleum and 71 g of 98% HNO3 at <20 °C for 1 hour under stirring wherein the concentration of nitric acid is 40%.
In accordance with the present disclosure, the fourth predetermined temperature is in the range of 5°C to 40°C. In an exemplary embodiment of the present disclosure, the fourth predetermined temperature is in the range of 10 °C to 30 °C.
In accordance with the present disclosure, the third predetermined time period is in the range of 10 hour to 15 hours. In an exemplary embodiment of the present disclosure, the third predetermined time period is 11 hours.
The schematic representation of the nitration of 2-Chloro-4-methylsulfonyl benzoic acid (IV) to obtain 2-Chloro-5-nitro-4-methylsulfonyl benzoic acid (V) in accordance with the present disclosure is given below as Scheme 1C.

Scheme 1C
Further, the so obtained 2-chloro-4-methylsulfonyl benzoic acid (IV) OR the so obtained 4-methylsulfonyl-2-chloro-5 nitro-benzoic acid (V) is condensed with m-cyano phenol (VI) by using at least one inorganic base in a second fluid medium in the presence of at least one second catalyst at a fifth predetermined temperature for a fourth predetermined time period to obtain ether of 2-chloro-4-methylsulfonyl benzoic acid (VII) OR ether of 4-methylsulfonyl-2-chloro-5 nitro- benzoic acid (VIII).
In accordance with the present disclosure, the inorganic base is at least one selected from the group consisting of sodium carbonate, potassium carbonate, and sodium bicarbonate. In an exemplary embodiment of the present disclosure, the inorganic base is potassium carbonate (K2CO3).
In accordance with the present disclosure, the second fluid medium is at least one selected from the group consisting of DMF (dimethylformamide), methanol, ethanol, toluene, and benzene. In an exemplary embodiment of the present disclosure, the second fluid medium is DMF (dimethylformamide).
In accordance with the present disclosure, the second catalyst is at least one selected from the group consisting of pyridine, copper powder, copper iodide (CuI), copper bromide (CuBr) and copper oxide (CuO). In an exemplary embodiment of the present disclosure, the second catalyst is a combination of pyridine, copper powder, and copper iodide.
In accordance with the present disclosure, the fifth predetermined temperature is in the range of 10 °C to 50 °C. In an exemplary embodiment of the present disclosure, the fifth predetermined temperature is 30 °C.
In accordance with the present disclosure, the fourth predetermined time period is in the range of 5 hours to 15 hours. In an exemplary embodiment of the present disclosure, the fourth predetermined time period is 10 hours.
The schematic representation of the condensation of 2-Chloro-4-methylsulfonyl benzoic acid (IV) with m-cyano phenol (VI) to obtain ether of 2-chloro-4-methylsulfonyl benzoic acid (VII) in accordance with the present disclosure is given below as Scheme 1D;

Scheme 1D
The schematic representation of the condensation of 2-chloro-5-nitro-4-methylsulfonyl benzoic acid (V) with m-cyano phenol (VI) to obtain ether of 4-methylsulfonyl-2-chloro-5 nitro- benzoic acid (VIII) in accordance with the present disclosure is given below as Scheme 1E:

Scheme 1E
In a final step, the ether of 2-chloro-4-methylsulfonyl benzoic acid (VII) OR the ether of 4-methylsulfonyl-2-chloro-5 nitro- benzoic acid (VIII) is cyclized by using at least one cyclizing agent at a sixth predetermined temperature for a fifth predetermined time period to obtain xanthone compounds of Formula (I).
In accordance with the present disclosure, the cyclizing agent is POCl3.
In accordance with the present disclosure, the sixth predetermined temperature is in the range of 80 °C to 120 °C. In an exemplary embodiment of the present disclosure, the sixth predetermined temperature is 100 °C.
In accordance with the present disclosure, the fifth predetermined time period is in the range of 4 hours to 8 hours. In an exemplary embodiment of the present disclosure, the fifth predetermined time period is 6 hours.
The schematic representation of the cyclization of ether of 2-chloro-4-methylsulfonyl benzoic acid (VII) to obtain the xanthone compound, 1-cyano-6-(methylsulfonyl) -9H-xanthen-9-one in accordance with the present disclosure is given below as Scheme 1F;

Scheme 1F
The schematic representation of the cyclization of ether of 4-methylsulfonyl-2-chloro-5 nitro-benzoic acid (VIII) to obtain the xanthone compound, 1-cyano-6-(methylsulfonyl)-7-nitro-9H-xanthen-9-one in accordance with the present disclosure is given below as Scheme 1G.

Scheme 1G
The process of the present disclosure employs inorganic bases during condensation step which are cheaper than organic bases and therefore, the process of the present disclosure is cost-efficient and economical. The inorganic bases used in the process of the present disclosure are easily separated.
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 purpose only and not to be construed for limiting the scope of the disclosure. The following experiments are scalable to industrial/commercial process.
EXPERIMENTAL DETAILS
Example 1: Preparation of 1-Cyano-6-(methylsulfonyl)-9H-xanthen-9-one (Formula I) in accordance with the process of the present disclosure
Step (i): Preparation of 2-Chloro-4-methylsulfonyl toluene (III)
350 g of 96% H2SO4 was added into a reactor followed by the addition of 170 g of 4-(Methylsulfonyl) toluene to obtain a mixture. The mixture was heated to a temperature of 85°C to obtain a clear solution. 142 g of Cl2 gas was passed slowly into the so obtained clear solution for 10 hours maintaining the temperature of 85°C to obtain a reaction mixture. The reaction mixture was further stirred for 2 hours to obtain a product mixture comprising 2-Chloro-4-methylsulfonyl toluene (III).
The reaction was monitored by HPLC. The reaction was stopped when HPLC showed absence of 4-methanesulfonyl toluene.
The product mixture was drowned in water, stirred and was filtered followed by washing with water to obtain a cake. The cake was reslurried in water, stirred and adjusted to pH 7 by using NaHCO3 and was again filtered to obtain a residue. The residue was washed with water; and the solids so obtained was dried in an oven to obtain 2-chloro-4-methylsulfonyl toluene (III) having a dry weight 203 g.
The purity of 2-Chloro-4-methylsulfonyl toluene was 95% and the yield was 94%.
Step (ii): Preparation of 2-chloro-4-methylsulfonyl benzoic acid (IV)
215 g of 2-Chloro-4-methylsulfonyl toluene (III) and 300 g of acetic acid were charged into a pressure reactor to obtain a mixture. To the mixture, 15 g of Co(OAC)2.4H2O, 10 g of Mn(OAc)2 and 5 g of NaBr were added as a catalyst and stirred to obtain a reaction mixture. To the reaction mixture, oxygen with a pressure of 5 kg/cm2 was passed and the reactor was heated to a temperature of 150°C and maintained at 150 oC for 60 minutes. Further, the oxygen was continuously passed into the reaction mixture in the reactor to attain a pressure of 20 kg/cm2 and further the reaction mixture was heated to a temperature of 160°C till no more consumption of oxygen was required, to obtain a reaction product comprising 2-chloro-4-methylsulfonyl benzoic acid (IV).
The reaction was stopped when the reaction product showed 2-Chloro-4-methylsulfonyl toluene = 1%.
After analysis of the reaction product, acetic acid was distilled out from the reaction product. After distilling out, the acetic acid from the reaction product, water was added and cooled to a temperature of 10°C under stirring, and filtered to obtain solids. The so obtained solids were washed with water to obtain a wet cake. The wet cake was purified by using alkali/water and reslurried with 500 ml water wherein a pH of the reslurried wet cake was adjusted to 12 by adding NaOH under stirring and again filtered to remove the insoluble portion and a filtrate. The insoluble portion was washed with water to obtain a washing in water. The filtrate and washing were combined and were acidified to adjust to pH 1 by using HCl under stirring to obtain slurry. The slurry was filtered to obtain solids. The solids were washed with water and after washing with water, the washed solids were dried in an oven to obtain 2-chloro-4-methylsulfonyl benzoic acid (IV) having a dry weight of solids 218 g.
The purity of 2-chloro-4-methylsulfonyl benzoic acid was 97% and the yield was 90%.
Step (iii): Preparation of ether of 2-chloro-4-methylsulfonyl benzoic acid (VII)
400 ml of DMF was charged into a reactor followed by adding 58 g of anhydrous potassium carbonate into the reactor to obtain a mixture. 26 g of m-cyano phenol was added to the mixture and stirred for 1 hour to obtain a resulting mixture. Further, 4 g of pyridine, 2 g Copper powder and 2 g of CuI as catalyst were added to the resulting mixture, followed by adding 48 g of 2-Chloro-4-methyl sulfonyl benzoic acid (having 97% purity obtained in step (ii)) and stirred at a temperature of 30°C for 10 hours. to obtain a product mixture comprising ether of 2-chloro-4-methylsulfonyl benzoic acid.
The product mixture comprising the ether of 2-chloro-4-methylsulfonyl benzoic acid was drowned in water, and was filtered to obtain a filtrate. The pH of the filtrate was adjusted to 1 by adding 95 ml of conc. HCl to obtain a precipitated mixture. The precipitated mixture was filtered to obtain a residue. The residue was washed with water and dried in an oven to obtain a dried ether of 2-chloro-4-methylsulfonyl benzoic acid having a dry weight of solids of 32 g.
The purity of ether of 2-chloro-4-methylsulfonyl benzoic acid (VII) is 98% and the yield was 67%.
Step (iv): Preparation of 1-cyano-6-(methylsulfonyl)-9H-xanthen-9-one (Formula I, when R is H)
100 ml of POCl3 was charged into a reactor and 20 g of the ether of 2-chloro-4-methylsulfonyl benzoic acid (VII) was added into the reactor to obtain a mixture. The mixture was heated to a temperature of 100°C under stirring for 6 hours to obtain a product mixture comprising 1-cyano-6-(methylsulfonyl) -9H-xanthen-9-one.
The product mixture was slowly drowned into 1000 ml water under stirring and heated to a temperature of 50°C for 1 hour under stirring to obtain slurry. The slurry was cooled to a temperature of 30°C, filtered and washed with water to obtain solids. The so obtained solids were reslurried with water and neutralized with sodium bicarbonate (NaHCO3) under stirring and again filtered, washed with water, followed by drying to obtain dried 1-cyano-6-(methyl sulfonyl) -9H-xanthen-9-one.
The dried 1-Cyano-6-(Methylsulfonyl)-9H-Xanthen-9-one was added into 75 ml of methylene di-chloride (MDC) under stirring, followed by filtration to remove insolubles (if any), to obtain a filtrate and further washed the insolubles with MDC to obtain washings. The filtrate and washings were concentrated to obtain 5g of 1-cyano-6-(methyl sulfonyl)-9H-xanthen-9-one.
The purity of 1-Cyano-6-(Methyl sulfonyl)-9H-Xanthen-9-one was 97% and the yield was 26.5%.
Example 2: Preparation of 1-cyano-6-(methylsulfonyl)7-nitro-9H-xanthen-9-one (Formula I) in accordance with the process of the present disclosure
1-cyano-6-(methyl sulfonyl)-7-nitro-9H-xanthen-9-one was prepared similar to Example 1, except nitration step of 4-methanesulfonyl-2-chloro benzoic acid to obtain 4-methanesulfonyl-2-chloro-5-nitro benzoic acid, was carried prior to the condensation step and cyclization step.
Preparation of mix acid used for nitration in accordance with the present disclosure:
100 g of 24% oleum and 71 g of 98% HNO3 were mixed at 15 °C for 1 hour under stirring to obtain mix acid having a nitric acid concentration of 40%.
Nitration of 4-Methanesulfonyl-2-chloro benzoic acid to obtain 4-methanesulfonyl-2-chloro-5-nitro benzoic acid
100 g of 98% of H2SO4 was added into a reactor. 242 g of 4-Methanesulfonyl-2-chloro benzoic acid (solids having 95% purity obtained in step (ii) of Example 1) was added into the reactor to obtain a mixture. The mixture was stirred for 30 minutes at 25 oC and then cooled to 10°C followed by the addition of 170 g of mix acid, slowly, over a time period of 4 hours and maintain the temperature of 8-10°C to obtain a reaction mixture. The reaction mixture was further stirred at 10°C for 1 hour. The temperature of the reaction mixture was further raised to 30°C and stirred for 6hoursto obtain a product mixture comprising 4-methylsulfonyl-2-chloro-5-nitro-benzoic acid.
The product mixture comprising 4-methylsulfonyl-2-chloro-5 nitro- benzoic acid was drowned in ice water under stirring, filtered to obtain solids and washed the solids with water to obtain a cake. The so obtained cake was dried in an oven at 80°C to obtain dried 4-methylsulfonyl-2-chloro-5 nitro- benzoic acid having a dry weight of solids of 278 g.
The purity of 4-methanesulfonyl-2-chloro-5-nitro benzoic acid was 98% and the yield was 99%.
The so-obtained 4-methanesulfonyl-2-chloro-5-nitro benzoic acid having 98% purity undergo condensation steps in a similar way as that of example 1 to obtain ether of 4-methylsulfonyl-2-chloro-5 nitro benzoic acid having HPLC purity of 98% and yield of 65%, followed by cyclization step of the ether of 4-methylsulfonyl-2-chloro-5 nitro benzoic acid in a similar way as that of example 1 to obtain 1-cyano-6-(methyl sulfonyl)7-nitro-9H-xanthen-9-one, in accordance with the present disclosure.
The purity of 1-cyano-6-(methyl sulfonyl)7-nitro-9H-xanthen-9-one was 97% and the yield was 30%.
TECHNICAL ADVANCEMENTS
The present disclosure described herein above has several technical advantages including, but not limited to, the realization of a process for the preparation of xanthone compounds that
• is simple, efficient, and commercially scalable;
• employs inorganic bases which are cheaper than organic bases, so economical;
• employs inorganic bases which can be easily separated, so environmental friendly; and
• results in higher purity of the final product (xanthone compounds).
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 is 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.
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 are added and that many changes are 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:WE CLAIM:
1. A process for the preparation of xanthone compounds of Formula (I), said process comprising the following steps:

(Formula I)
wherein R is H, or NO2.
(i) chlorinating 4-(Methylsulfonyl)toluene by using at least one chlorinating agent and at least one mineral acid at a first predetermined temperature for a first predetermined time period to obtain 2-chloro-4-methylsulfonyl toluene;
(ii) oxidizing 2-chloro-4-methylsulfonyl toluene by using at least one oxidizing agent in a first fluid medium in the presence of at least one first catalyst at a second predetermined temperature for a second predetermined time period followed by heating at a third predetermined temperature to obtain 2-chloro-4-methylsulfonyl benzoic acid;
(iii) optionally nitrating 2-chloro-4-methylsulfonyl benzoic acid by using at least one nitrating agent at a fourth predetermined temperature for a third predetermined time period to obtain 4-methylsulfonyl-2-chloro-5 nitro- benzoic acid;
(iv) condensing 2-chloro-4-methylsulfonyl benzoic acid obtained in step (ii) or 4-methylsulfonyl-2-chloro-5 nitro- benzoic acid obtained in step (iii) with m-cyano phenol by using at least one inorganic base in a second fluid medium in the presence of at least one second catalyst at a fifth predetermined temperature for a fourth predetermined time period to obtain ether of 2-chloro-4-methylsulfonyl benzoic acid or ether of 4-methylsulfonyl-2-chloro-5 nitro- benzoic acid; and
(v) cyclizing said ether of 2-chloro-4-methylsulfonyl benzoic acid or said ether of 4-methylsulfonyl-2-chloro-5 nitro- benzoic acid by using at least one cyclizing agent at a sixth predetermined temperature for a fifth predetermined time period to obtain xanthone compounds of Formula (I).
2. The process as claimed in claim 1, wherein said chlorinating agent is at least one selected from the group consisting of chlorine gas, N-Chloro succinimide, and Sulfuryl chloride (SO2Cl2).
3. The process as claimed in claim 1, wherein said chlorinating agent is chlorine gas.
4. The process as claimed in claim 1, wherein said mineral acid is at least one selected from the group consisting of sulphuric acid, hydrochloric acid, and nitric acid.
5. The process as claimed in claim 1, wherein said mineral acid is sulphuric acid.
6. The process as claimed in claim 1, wherein said oxidizing agent is at least one selected from oxygen and air.
7. The process as claimed in claim 6, wherein oxygen is passed to a reactor with a pressure in the range of 1 kg/cm2 to 10kg/cm2 and heated to said second predetermined temperature followed by continuously passing oxygen in said reactor to attain a pressure in the range of 10 kg/cm2 to 30kg/cm2 and heating to said third predetermined temperature to obtain 2-chloro-4-methylsulfonyl benzoic acid.
8. The process as claimed in claim 1, wherein said first fluid medium is at least one selected from the group consisting of acetic acid, formic acid and oxalic acid.
9. The process as claimed in claim 1, wherein said first catalyst is at least one selected from the group consisting of cobalt acetate (Co(OAC)2.4H2O), manganese acetate (Mn(OAc)2) and sodium bromide (NaBr).
10. The process as claimed in claim 1, wherein said first catalyst is a mixture of cobalt acetate (Co(OAC)2.4H2O), manganese acetate (Mn(OAc)2) and sodium bromide (NaBr).
11. The process as claimed in claim 1, wherein said nitrating agent is selected from the group consisting of HNO3, H2SO4 and oleum.
12. The process as claimed in claim 1, wherein said inorganic base is at least one selected from the group consisting of sodium carbonate, potassium carbonate, and sodium bicarbonate.
13. The process as claimed in claim 1, wherein said second fluid medium is at least one selected from the group consisting of DMF (dimethylformamide), methanol, ethanol, toluene, and benzene.
14. The process as claimed in claim 1, wherein said second catalyst is at least one selected from the group consisting of pyridine, copper powder, copper iodide (CuI), copper bromide (CuBr) and copper oxide (CuO).
15. The process as claimed in claim 1, wherein said second catalyst is a combination of pyridine, copper powder, and copper iodide (CuI).
16. The process as claimed in claim 1, wherein said cyclizing agent is POCl3.
17. The process as claimed in claim 1, wherein
• said first predetermined temperature is in the range of 75 °C to 95 °C;
• said first predetermined time period is in the range of 8 hours to 12 hours;
• said second predetermined temperature and said third predetermined temperature are independently in the range of 130 °C to 170 °C;
• said second predetermined time period is in the range of 30 minutes to 120 minutes;
• said fourth predetermined temperature is in the range of 5 °C to 40 °C;
• said third predetermined time period is in the range of 10 hours to 15 hours;
• said fifth predetermined temperature is in the range of 10 °C to 50 °C;
• said fourth predetermined time period is in the range of 5 hours to 15 hours;
• said sixth predetermined temperature is in the range of 80 °C to 120 °C; and
• said fifth predetermined time period is in the range of 4 hours to 8 hours.

Dated this 08th day of September, 2023

_______________________________
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