FORM 2
THE PATENTS ACT, 1970
(39 OF 1970)
&
THE PATENTS RULES, 2003
COMPLETE SPECIFICATION
(See Section 10 and Rule 13)
A PROCESS FOR PREPARATION OF B1SPYRIBAC SODIUM
GHARDA CHEMICALS LTD
an Indian company
of B-27/29, MIDC Dombivli (East)
Thane - 421203, Maharashtra, India
Inventors:
1. MATHUR SUCHET S.
2. JAIN NANDKUMAR J.
3. MORE MAHENDRA M.
4. AHERSATYAWANB.
5. PADWAL SACHIN S.
THE FOLLOWING SPECIFICATION PARTICULARLY DESCRIBES THE INVENTION AND THE MANNERIN WHICH IT IS TO BE PERFORMED

FIELD OF DISCLOSURE
The present disclosure relates to a process for the preparation of Bispyribac-metal salts. The present disclosure particularly relates to a process for the preparation of Bispyribac-sodium.
BACKGROUND
Bispyribac-sodium
IUPAC Name: sodium 2, 6-bis (4, 6-dimethoxypyrimidin-2-yloxy) benzoate
Structure:

Chemical formula: C19H17NaO8
Molecular Weight: 452.4
Physical State: white powder
Melting point: 223-224°C
Solubility in water: 73.3g/l at 25°C
Mode of action: selective, systemic action post-emergence herbicide, absorbed by
foliage and roots.
Bispyribac sodium is a systemic herbicide used to control grasses, sedges and broad-leaved weeds, especially Echinochloa spp., in direct seeded rice. It is also used to stunt growth of weeds in non-crop situations.
Bispyribac sodium is degraded by microbes and has a half-life (the time it takes for half of the active ingredient to degrade) of 42-115 days. The primary degradation product of bispyribac sodium is sodium 2-(4, 6 dimethoxypyrimidin-2-yl) oxy-6-(4-hydroxy-6-methoxypyrimidin-2-yl) benzoate. Bispyribac sodium does not bind to

soil, is moderately persistent and somewhat mobile through the soil. Testing indicates that the aquatic formulation of bispyribac sodium is non-toxic to fish and invertebrates. Bispyribac sodium is also non-toxic to both birds and mammals.
Bispyribac-sodium is produced by reaction of 2,6-dihydroxybenzoic acid with a substituted derivative of 4,6-dimethoxypyrimidine.The prior art process utilize strong acids such as sulphuric acid and hydrochloric acid and also the time required for the reaction is very high. Furthermore, the known processes are low yielding.
Therefore, there is felt a need for a simple and economic process for the preparation of Bispyribac sodium.
OBJECTS
Main object of the present disclosure is to provide a simple and an economical process for the preparation of Bispyribac-metal salt.
Another object of the present disclosure is to provide a process for the preparation of Bispyribac- metal salt which obviates the use of strong acids.
Summary:
In accordance with the present disclosure there is provided a process for the preparation of Bispyribac sodium; said process comprises condensing 2,6-dihydroxy benzoic acid with 2-(alkyl sulfonyl)-4,6-dialkoxy pyrimidine in the presence of at least one base and at least one solvent.
In one embodiment the condensation is carried out at a temperature ranging between 20 and 80°C.
Typically, the base is selected from the group consisting of sodium hydride, potassium hydride, lithium and calcium hydride. In one embodiment the base is sodium hydride.

Typically, the solvent is selected from the group consisting of tetrahydrofuran, dimethylsulfoxide, dimethylformamide, dimethyl acetamide, N-methyl pyrrolidone, sulfolane, monoglyme and diglyme. In one embodiment the solvent is dimethylsulfoxide.
Typically, 2-(alkyl sulfonyl)-4, 6-dialkoxy pyrimidine is 2-(methyl sulfonyl)-4,6-dimethoxy pyrimidine.
Brief description of accompanying drawing:
Figure 1 illustrates a reaction scheme for the preparation of Bispyribac- metal salt in accordance with the present disclosure.
Description:
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 description herein after, of the specific embodiments will 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.
In accordance with the present disclosure there is provided a process for the preparation of Bispyribac-sodium. The process involves condensing 2.6-dihydroxy benzoic acid with 2-(alkyl sulfonyl)-4,6-dialkoxy pyrimidine in the presence of at least one base selected from the group consisting of sodium hydride, potassium hydride, lithium and calcium hydride and at least one solvent selected from the group consisting of tetrahydrofuran, dimethylsulfoxide, dimethylformamide, dimethyl acetamide, N-methyl pyrrolidone, sulfolane, monoglyme and diglyme to obtain Bispyribac- sodium. The condensation is carried out at a temperature ranging between 20 and 80°C. In one embodiment, the base employed in the condensation reaction is sodium hydride. The solvent employed in condensation reaction is dimethylsulfoxide. In accordance with the present disclosure 2-(alkyl sulfonyl)-4, 6-dialkoxy pyrimidine employed is 2-(methyl sulfonyl)-4, 6-dimethoxy pyrimidine.
The disclosure is further illustrated by way of the following non limiting examples.
Preparation of Bispyribac sodium
Exampie-1:
A clear solution of 154 gm of 2,6-dihydroxy benzoic acid in 500 ml Dimethyl sulfoxide is added over 2-3 hr into a mixture of commercial available (60% emulsion in oil) 130 gm of Sodium hydride in 2 lit. of Dimethyl sulfoxide at 30-32°C . Mass is further stirred for 2 hr at 30-32°C and 480 gm of 4,6-Dimethoxy-2-(Methyl Sulfonyl)-pyrimidine is added into it over 2 hr. Reaction is maintained at 30-32°C till completion to get Bispyribac sodium. The reaction was monitored by HPLC. Mass is filtered, washed with DMSO. Wet solids were reslurried into 1000 ml of methanol & then in 1000 ml of 75% aq. Methanol. Wet solids were dried in oven to get 435 gm of Bispyribac sodium. This Bispyribac sodium is reslurried into 1200 ml of Toluene at reflux temperature, cooled, filtered & dried to give 385 gm of Bispyribac sodium ( purity 98.7% HPLC).

Example-2:
A clear solution of 154 gm of 2,6-dihydroxy benzoic acid in 500 ml. Dimethyl sulfoxide is added over 2-3 hr into a mixture of commercial available (60% emulsion in oil) 130 gm of Sodium hydride in 1500 ml of Dimethyl sulfoxide at 30-32°C . Mass is further stirred for 2 hr at 30-2°C and a slurry of 480 gm of 4,6-Dimethoxy-2-(Methyl Sulfonyl)-pyrimidine into 750 ml of DMSO is added into it over 2-3 hr. Reaction is maintained at 30-32°C till completion to get Bispyribac sodium. The reaction was monitored by HPLC. Mass is filtered, washed with DMSO. Wet solids were reslurried into 1000 ml of methanol & then in 1000 ml of 75% aq. Methanol. Solids were dried in oven to get 430 gm of Bispyribac sodium. This Bispyribac sodium powder is reslurried into 1200 ml of Toluene at reflux temperature, cooled, filtered & dried to get 380 gm of Bispyribac sodium (purity 98.3% HPLC).
Example-3:
A clear solution of 154 gm of 2, 6-dihydroxy benzoic acid in 500 ml of Dimethyl sulfoxide is added into a mixture of 130 gm of commercial available (60% emulsion in oil) Sodium hydride in 1500 ml of Dimethyl sulfoxide at 30-32°C . Mass is further stirred for 2 hr at 30°C and a slurry of 480 gm of 4,6-Dimethoxy-2-(Methyl Sulfonyl)-pyrimidine into 750 ml of DMSO is added into it. Reaction is maintained at 30-32 C till completion to get Bispyribac sodium. Mass is filtered, washed with DMSO. Wet solids were reslurried into 1000 ml of methanol & then in 1000 ml of 75% aq. Methanol. Solids were dried in oven to get 440 gm of Bispyribac sodium. This Bispyribac sodium powder is reslurried into 1200 ml of Toluene at reflux temperature, cooled, filtered & dried to get 380 gm of Bispyribac sodium, (purity 98.5% HPLC).
Example-4:
A clear solution of 154 gm of 2,6-dihydroxy benzoic acid in 500 ml of Dimethyl sulfoxide is added into a mixture of 130 gm of commercial available (60% emulsion in oil) Sodium hydride in 2 lit of Dimethyl sulfoxide at 30-32DC . Mass is further stirred for 2 hr at 30°C and slurry of 480 gm of 4,6-Dimethoxy-2-(Methyl Sulfonyl)-pyrimidine into 750 ml of DMSO is added into it. Reaction is maintained at 30-32°C

till completion to get Bispyribac sodium. Mass is filtered, washed with DMSO. Wet solids were reslurried into 1000 ml of methanol & then in 1000 ml of 75% aq. Methanol. Solids were dried in oven to get 435 gm of Bispyribac sodium. This Bispyribac sodium powder is reslurried into 1200 ml of Toluene at reflux temperature, cooled, filtered & dried to get 385 gm of Bispyribac sodium (purity 98.6% HPLC).
Example-5:
A clear solution of 154 gm of 2, 6-dihydroxy benzoic acid in 500 ml of Dimethyl sulfoxide is added into a mixture of 130 gm of commercial available (60% emulsion in oil) Sodium hydride in 1500 ml of Dimethyl sulfoxide at 30-32°C. Mass is further stirred for 2 hr at 30°C and a clear solution of 480 gm of 4,6-Dimethoxy-2-(Methyl Sulfonyl)-pyrimidine into 1500 ml of DMSO is added into it. Reaction is maintained at 30-32°C till completion to get Bispyribac sodium. Mass is filtered, washed with DMSO. Wet solids were reslurried into 1000 ml of methanol & then in 1000 ml of 75% aq. Methanol. Solids were dried in oven to get 400 gm of Bispyribac sodium. This Bispyribac sodium powder is reslurried into 1200 ml of Toluene at reflux temperature, cooled, filtered & dried to get 350 gm of Bispyribac sodium (purity 98.6% HPLC).
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.
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 invention. It is not to be taken as an admission that any or all of these matters form

part of the prior art base or were common general knowledge in the field relevant to the invention as it existed anywhere before the priority date of this application.
"Whenever a range of values is specified, a value up to 10 % below and above the lowest and highest numerical value respectively, of the specified range, is included in the scope of the disclosure".
While considerable emphasis has been placed herein on 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 embodiments 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 forgoing descriptive matter to be implemented merely as illustrative of the disclosure and not as limitation.
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. 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 invention. It is not to be taken as an admission that any or all of these matters form part of the prior art base or were common general knowledge in the field relevant to the invention 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.

WE CLAIM:
1. A process for the preparation of Bispyribac sodium; said process comprises condensing 2,6-dihydroxy benzoic acid with 2-(alkyl sulfonyI)-4,6-dialkoxy pyrimidine in the presence of at least one base and at least one solvent.
2. The process as claimed in claim 1, wherein the base is selected from the group consisting of sodium hydride, potassium hydride, lithium and calcium hydride
3. The process as claimed in claim 1, wherein the condensation is carried out at a temperature ranging between 20 and 80°C.
4. The process as claimed in claim 1, wherein the solvent is selected from the group consisting of tetrahydrofuran, dimethylsulfoxide, dimethylformamide, dimethyl acetamide, N-methyl pyrrolidone, sulfolane, monoglyme and diglyme.
5. The process as claimed in claim 1. wherein 2-(alkyl sulfonyl)-4,6-dialkoxy pyrimidine is 2-(methyl sulfonyl)-4,6-dimethoxy pyrimidine.
6. The process as claimed in claim 1, wherein the base is sodium hydride.
7. The process as claimed in claim 1, wherein the solvent is dimethylsulfoxide.