Title of Invention

"AN IMPROVED PROCESS FOR SYNTHESIS OF DISUBSTITUTED PYRIDINE-N-OXIDE AND PRODUCTS THERE OF"

Abstract

An improved process for synthesis of the disubstituted pyridine-N-oxides, which comprises in the steps of, dissolving 3 alkyl-pyridine-N-oxide in a solvent as herein described, adding a nitrating agent as herein described to the said solution, heating the acidic reacting solution to a first stage temperature as herein described followed by raising the reaction temperature to a second stage as herein described, said acidic reacting solution being neutralised with a neutralising agent as herein described to obtain disubstituted pyridine-N-oxides which is filtered, washed and dried, preferably, under vacuum.

Full Text

FIELD OF THE INVENTION The present invention relates to the improved process for synthesis of d isubstituted-pyridine-N-oxides. particularly to the synthesis of 3,4-disubstituted pyndine-N-oxides, more particularly to 3-a 1ky1-4-nitro-substituted pyndine-N-Dxides and to the products thereof. BACKGROUND OF THE INVENTION There is increasing interest in the research leading to synthesis of non-linear optical materials. These non-linear optical materials find their wide applications in the second harmonic generation, frequency mixing, optical parametric oscillation etc. The organic materials have shown better non-linear effects far exceeding those of their inorganic counterparts. The organic crystals have shown still better non-linear effects among -the organic materials. The substituted pyridine-N-ox ide has shown such properties. Therefore, the need was observed to have process ifor synthesising the substituted pyridine-N-oxides, particularly the disubst ituted pyr'idine-N-oxides, more particularly 3-alkyl-4-nitro-»ubstituted pyridine-N-oxides. The known such disubstituted pyridine-N-oxides having nitro-group in para-position, that is in position-4, have been synthesised by nitrating the mono-substituted pyridine-N-oxide compounds. The nitration of such mono-substituted pyridine-N-oxides in known such methods of the prior art has been carried out by using commonly used fuming nitric acid as nitrating agent. The major disadvantage of such known process of the prior art, wherein the nitrating agent is fuming acid is that, the process by itself is cumbersome as known in the prior art. The another drawback of such known process of prior art as stated above, is that, such process results in the reduction of the overall yield of the final product, more particularly in reduction of the percent yield of the final product which inturn results in the increase in the cost of production of the final product. The another drawback of known process of prior art where the nitrating agent is mixture pf potassium nitrate / and concentrated sulphuric acide, is that, the .potassium nitrate results in formation of potassium -ylphsfp, turn is less soluble in water, so remains as an impurity in final product, necessitating its extraction with chloroform. Still another drawback of such known process of orior art as stated above, is that, the neutralisation of acidic solution is carried-out by potassium hydroxide and the final product thus resulted, contains large quantities of impurities. The low purity thus resulted, in-turn results in the poor performance of the final product, that is, of the non-linear optical material. Yet another disadvantage of known such process, comprising of potassium nitrate as part of nitrating agent and potassium hydroxide as neutralising agent, is that, the potassium salts results in formation of potassium sulphate, as described herein above, and formation of potassium sulphate during the synthesis definitely results in decrease in purity and yield of the final product. Further drawback of such known process of the prior art', as stated above, is that, the purity of the final product is inhanced by extrating the final product in x chloroform. This extraction not only results in increase in number of reaction steps, but also results in further reduction of overall yield, more particularly of the percent yield of the final product. ' i In addition to above drawbacks, as described herein above, the extraction step consumes large volumes of solvent, that is, chloroform. Hence, results in further increase in cost of the process. Further the use of chloroform as solvent makes the process health hazardous. NEED OF THE INVENTION Therefore, there is a need for the development of an improved process for the synthesis of the substituted pyridine-N-oxides, particularly for the synthesis of the disubstituted pyridine-N-oxides, more particularly for the synthesis of 3, 4-disubstituted pyridine-N-oxides, even more particularly for the synthesis of 3-alkyl-4-nitro-pyridine-N-oxides, which can overcome the drawbacks of the such known process of the prior art. OBJECTS DF THE INVENTION This is the primary object of the present invention to make a complete disclosure of the process for the synthesis of the substituted pyridine-N-oxides, particularly for synthesis of the disubstituted pyridine-N-oxides, more particularly for the synthesis of 3,4-disubstituted pyridine-N-oxides, even more particularly for the synthesis of 3-alkyl-4-nitro-pyridine-N-oxides and of the products thereof. This is another an object of the present invention to make a complete disclosure of the process for the synthesis i • of the substituted pyridine-N-oxides, particularly for synthesis of 3,4-disubstituted pyridine-N-oxides, particularly for the synthesis of 3-alkyl-4-nitro-pyridine-N-oxides, and products thereof, as stated herein above, wherein the disadvantages and drawbacks of the prior art, as described herein abovp, are reduced t.n fhp m?jor pxtpnt. Further an object of the present invention to make a complete disclosure of the-process for the synthesis of the substituted pyridine-N-oxides, particularly for synthesis of 3,4-disubstituted pyridine-N-oxides, more particularly for the synthesis of 3-alkyl-4-nitro-pyridine-N-oxides, and products thereof, as stated herein above, wherein the step of extraction of the final product with chloroform is totally eliminated, and hence, the drawbacks of this step. as stated herein above are totally eliminated. In addition this is further an object of this invention to avoid the steps of isollation totally and hence reducing the number of steps, thus resulting in reduction of total number of steps of the overall process disclosed in this invention. Still further an object of the present invention to make a complete disclosure of the process for the synthesis of the substituted pyridine-N-oxides, particularly for synthesis of 3,4-disubstituted pyridine-N-oxides, more particularly for the synthesis of 3-alky1-4-nitro-pyridine-N-oxides, and products thereof, as stated herein above, wherein the use of potassium nitrate as nitrating agent and fuming nitric acid as one part of the nitrating agent, and further the use of potassium hydroxide as neutralising agent are totally avoided, hence the formation of potassium sulphate is definitely avoided as one of impurity or say by¬product . This is the main object of present invention to make a complete disclosure of the process for the synthesis of the substituted pyridine-N-oxides, particularly for synthesis of 3,4-disubstituted pyridine-N-oxides, particularly for the synthesis of 3-alkyl-4-nitro-pyridine-N-oxides, and products thereof, as stated herein above, wherein the overall yield, particularly the percent yield of the final product is definitely improved and the purity of the final product 1= relatively higher, which inturn results in the better performance of the final product. This is definitely an advantage of the presently disclosed invention present invention to make a complete disclosure of the process for the synthesis of the substituted pyridine-N-oxides, particularly for synthesis of 3, 4-disubstituted pyridine-N-oxides, particularly for the synthesis of 3-alkyl-4-nitro-pyridine-N-oxides, and products thereof, as states herein above, wherein the overall cost of the process and the cost of the final product is very low, hence the process proposed in the present invention is highly economical, and the process disclosed in present invention is easy to perform, time saving and non-hazardous. STATEMENT OF INVENTION According to this invention there is provided an improved process for synthesis of the disubstituted pyridine-N-oxides, which comprises in the steps of dissolving 1 to 1.5 mole of 3 alkyl-pyridine-N-oxide in a solvent as herein described at a temperature between 65-70°C, adding 1.5 to 2.5 mole of nitrating agent as herein described to the said solution, heating the acidic reacting solution at a temperature of 95°C followed by raising the reaction temperature to 105°C herein described, said acidic reacting solution being neutralised with 15 moles, preferably 13 moles of neutralising agent as herein described to obtain disubstituted pyridine-N-oxides which is filtered, washed and dried, preferably, under vacuum. BRIEF OF THE INVENTION In accordance to the present invention a complete disclosure is made for the process of synthesis of the substituted pyridine-N-oxides, particularly for the synthesis of the disubstituted pyridine-N-oxides, more particularly for the synthesis of 3, 4-disubstituted pyridine-N-oxides, even more particularly for the synthesis of 3-alkyl-4-nitro-pyridine-N-oxides and for the products made thereof, which inturn primarily comprises of one step and inturn is carried out in following stages:- (a) the mono-substituted pyridine-N-oxide is dissolved in the acidic solvent, (b) the nitrating agent is added to the acidic solution of mono- substituted pyridine-N-oxide of stage 'a'. (c) the reaction mixture's temperature is raised to 105 degree celsius in two stages. (d) the reacted mass is neutralised after cooling to temperature lower than room temperature, (e) the final product is filtered, washed and dried under vacuum. The present invention makes the complete disclosure of the process for syntheses of the disubstituted pyridine-N-oxides, particularly for the synthesis of 3,4-disubstituted pyridine-N-oxides, more particularly for the synthesis of 3-alkyl-4-nitro-pyridine-N-oxides and for the products made thereof which definitely provides the following advantages over the known much processes of the prior art: a) The nitrating agent is sodium nitrate or ammonium nitrate, preferably ammonium nitrate, b) sulphuric acid serves two purposes, one as solvent for mono-substituted pyridine-N-oxide and second as one of the component of the nitrating agent, c) neutralisation agent is aqueous ammonia, d) the final product is directly obtained after filteration, washing and is dried under vacuum. The presently disclosed process for the synthesis of 3,4-disubstituted pyridine-N-oxides, particularly for the synthesis of 3-alkyl-4-nitro-pyridine-N-oxides, as described herein above, definitely eliminates the step of solvent extraction and improve the overall yield, particularly the percent yield of the final product and avoids formation of potassium sulphate altogether and hence results in increase in the purity of the final product, and these result in reduction in overall cost of the process of synthesis and the final1 product as it is clear from the foregoing description of this invention. DESCRIPTION QF. THE INVENTION The presently disclosed invention makes the complete disclosure of the process for synthesis of the d isubstituted pyrridine-N-oxides, particularly for the synthesis of 3,4-disubstituted pyridine-N-oxides, more particularly for the synthesis of 3-alky1-4-nitro-pyridine-N-oxides and for the products made thereof, wherein said process comprises of one step and is carried out in single vessel in following stages: a) 3-alkyl pyridine-N-oxide, herein after referred as 'A', is slowly added to concentrated sulphuric acid, herein after referred on 'S' already taken in three neck round bottom flask, herein after referred as 'r.b.f', carrying a magnetic bead and fitted with thermometer in one neck and condenser with water circulation in another neck, and placed on an oil bath, which in-turn is placed on a hot plate-cum-magnetic stirrer. The reaction mixture is slowly stirred and temperature is essentially maintained below 70 degree celcius. b) To the reacting solution of stage'a', the nitrating agent, herein after referred as 'B', is added slowly from the third opening of the r.b.f., while maintaining the reacting solution's temperature below 7O degree celcius. c) After complete addition of 'B' in stage-b the temperature of the reacting solution is raised to 95 degree celcius and the reaction is allowed to continue for 5-15 hrs, preferably for 6-11 hrs. d) 'After the reaction ,has been allowed to continue for 5- 15 hrs, preferably for 6-11 hrs in stage-'C' the temperature of the reacting solution is raised to 1O5 degree celcius, and reaction is allowed to continue further for additional 1-2 hrs. e) The acidic solution after stage-d, is allowed to cool to room temperature and is further cooled to bring the; temperature less than 15 C by adding to it crushed ice or preferably pouring slowly, the acidic solution already cooled to room temperature, to the beaker containing' 'crushed ice' f) The cold reaction mass of stage 'e' is neutralised with the help of cold aqueous ammonia solution. g) The final product, that is, 3-alkyl-4-nitro-pyridine-N- oxide from reaction mixture at stage-f, is filtered and washed with cold distilled water and dried preferably under vacuum. As it is clear from the above description making a complete disclosure of the process of the present invention the whole synthetic process is completed in single reaction vessel and in one step only and further it eliminates all disadvantages and drawbacks of such known processes of the prior art. The 3-alky1-pyridine-N-oxide is taken in 1 mole to 1.5, -2.5 moles ratio of nitrating agent. The alkyl group of pyridine-N-oxide is electron donating group preferably having 1 to 3 carbon atoms, like, -CH3, -CH2-CH3, -CH2-CH2-CH3, -CH(CH3>2. However, the alkyl group may have 4 or more carbon atoms. The nitrating agent is sodium nitrate or ammonium nitrate, preferably ammonium nitrate. The solvent, that is sulphuric acid is taken in excess. For 1 male of A, S is taken from 9.0 moles to 15 moles, preferably 10.0 moles to 13 moles. The neutralising agent is aqueous ammonia and taken in excess upto 15 moles, preferably upto 13 moles. The presently disclosed invention is illustrated, herein below, with the help of the examples just to demonstrate the working of the present invention. These examples are not intended to limit the scope of the present invent ion. Example-.l 1 mole of 3-methy1-pyridine-N-oxide is dissolved slowly in 1000 g of concentrated sulphuric acid in two litre, three neck r.b.f. maintaining the temperature between 65-70 degree celcius. 153 g of sodium nitrate is added while the temperature is kept between 65-70 degree celcius. The reaction mixture is heated to 95 C and maintained at this temperature for 15 hours, again heated to 105 C and maintained at this temperature for 2 hours. The reaction mixture is cooled to temperature Examp1e-2 109 g of 3-methyl-pyridine-N-oxide is dissolved slowly in 1000 g of concentrated sulphuric acid in two litre, three neck r.b.f. mitintaining1 the temperature between 65-70 degree celcius. 144 q of ammonium nitrate is added while the temperature is kept between 65-7O degree, celcius. The reaction mixture is heated to 95 C and maintained at this temperature far 15 hours, again heated to 105°C and maintained at this temperature for 2 hours. The reaction mixture is cooled to temperature Example 3_ 1 mole of 3-methy1-pyridine-N-oxide is dissolved slowly in 10.5 moles of concentrated sulphuric acid in two litre, three neck r.b.f. maintaining the temperature between 65-70 degree celcius. 1.9 moles of sodium nitrate is added while the temperature is kept between 65-70 degree celcius. The reaction mixture is heated to 95 C and maintained at this temperature for 7 hours, again heated to 105 C and maintained at this temperature for 1 hours. The reaction mixture is cooled to temperature WE CLAIM: 1. An improved process for synthesis of the disubstituted pyridine-N-oxides, which comprises in the steps of : a) dissolving 1 to 1.5 mole of 3 alkyl-pyridine-N-oxide in a solvent as herein described at a temperature between 65-70°C, b) adding 1.5 to 2.5 mole of nitrating agent as herein described to the said solution, c) heating the acidic reacting solution at a temperature of 95°C followed by raising the reaction temperature to 105°C herein described, b) said acidic reacting solution being neutralised with 15 moles, preferably 13 moles of neutralising agent as herein described to obtain disubstituted pyridine-N-oxides which is filtered, washed and dried, preferably, under vacuum. 2. A process for the synthesis of disubstituted pyridine-N-oxides as claimed in claim 1 wherein, the said solvent is concentrated sulphuric acid and is taken in excess from 9.0 moles to 15 moles, preferably from 10.0 moles to 13.0 moles for each mole of 3-alkyl- pyridine-N-oxide. 3. A process as claimed in claim 1 wherein the said nitrating agent is sodium nitrate or ammonium nitrate, preferably ammonium nitrate and is taken in 1.5 moles to 2.5 moles for each mole of 3-alkyl- pyridine-N-oxide. 4. A process as claimed in claims 1 to 6 wherein the said reaction is allowed to continue for 5-15 hours, preferably for 6-11 hours at 95 degree celcius temperature and for 1-2 hours at 105 degree celcius temperature. 5. A process as claimed in preceeding claims wherein the said neutralising agent is aqueous ammonia solution as herein described and is taken in excess upto 15 moles, preferably upto 13 moles. 6. A process as claimed in preceeding claims wherein said neutralising agent is added essentially after cooling the said acidic reaction solution to temperature less than 15 degree celcius preferably pouring the said acidic reaction solution over the crushed ice. 7. A process as claimed in preceeding claims wherein the said alkyl group is electron donating group, preferably having 1-3 carbon atoms, like-CH3 , -CH2 , -CH3 , CH2 , -CH2 , -CH3 , -CH(CH3 )a. 8. A process as claimed in claim 1 wherein said steps of filtration is carried out after reducing the temperature of the said neutralised reaction mixture to 10-15 degree celcius. 9. An improved process for the synthesis of disubstituted pyridine-N- oxides substantially as herein described, the foregoing description and examples. Q

Documents:

196-del-1997-abstract.pdf

196-del-1997-claims.pdf

196-DEL-1997-Correspondence-Others-(19-08-2010).pdf

196-del-1997-correspondence-others.pdf

196-del-1997-correspondence-po.pdf

196-del-1997-description (complete).pdf

196-del-1997-form-1.pdf

196-DEL-1997-Form-15-(19-08-2010).pdf

196-del-1997-form-19.pdf

196-del-1997-form-2.pdf

196-del-1997-form-3.pdf

196-del-1997-gpa.pdf