Title of Invention

AN IMPROVED POCESS FOR THE PREPARATION OF 2-HYDROXY QUINOXALINE"

Abstract

An improved process for the preparation of 2 - hy - droxy quinoxaline of the formula 5 which comprises adding water miscible polar solvent to l,2,3,4-tetrahydro-s-ketoquinoxaline-4N-acetic acid, of the formula 4 reacting the misture with an oxidizing agent, stirring the reacting mixture, for a period in the range of 4-10 hours filtering and extracting the re-sultant product using a polar solvent which is not miscible with water by conventional methods, washing the solvent layer with water, drying, distilling the solvent under reduced pressure and crystallizing by known methods to obtain 2-hydroxy quinoxaline.

Full Text

The invention relates to an improved process for the production of 2-hydroxy quinoxaline. The present invention particularly relates to an improved process for the preparation of 2-hydroxyquinoxaline from 1,2,3,4-tetrahydroquinoxaline -N-acetic acid (a waste or effluent in the production of 2-keto-1,2,3,4 -tetrahydro-quinoxaline). The 2-hydroxyquinoxaline prepared by the process of the present invention is an important starting material in the production of qui-nalphos which is an important compound of the organo-phosphorus group of pesticide. Hitherto 2-hydroxyquinoxaline is prepared by the methods described below. Glyoxalic acid method [European Patent 444619 (1990) : CA 115 232291 s] According to the method disclosed in the above-said patent orthophenylene diamine is reacted with glyoxalic acid in methanol to give 2-hydroxyquinoxaline in one step and in 90% yield. The main drawback of this method is that it uses glyoxalic acid which is not industrially economical. It is a corrosive chemical and tends to polymerize, posing problem in storing. Ethyl glyoxalate method [J. Org. Chem. (1951) ,,16, 438;] In the method described in the above-mentioned journal ethyl ester of glyoxalic acid is used to prepare 2-hydroxyquinoxaline from orthophenylene diamine. The drawback of this method is that it involves the step of the esterification of glyoxalic acid, affecting the economics of the process. Butyl glyoxalate method [J. Chem. Soc.(1956),26; In the process described in the above-mentioned journal orthophenylene diamine is condensed with butyl glyoxalate in ethanol under refluxed condition to produce 2-hydroxyquinoxaline in 94% yield. The drawback of this method is that it requires another tedious step of reaction for production of n-butylglyoxalate which requires chemicals like sodium toluene-p-sulphonate, N-sulphuric acid, benzene, tartaric acid and butanol. Butyl tartrate method [US Patent 4450271 (1984); CA 101, 72761 a] According to the method dibutyl tartrate is first oxidized with sodium periodate at elevated temperature to generate butyl glyoxalate which is then condensed with orthophenylene diamine to give 2-hydroxyquino xaline. The drawback of the method is that the yield is poor (67%) . The oxidation of dibutyl tartrates with alkali per iodex for generating dibutyl glyoxalate involves a separate step of the process. The addition of another chemical, sodium periodate makes the process uneconomical. Several oxidation methods have also been reported tor oxidation ot 2-hydroxyqumoxalme in the literature. Hydrogen peroxide method In this method 2-ketotetrahydroquinoxaline is oxidized with hydrogen peroxide in methanol at 50° in presence of Ferrous sulphate for about 12 hours to get 2-hydroxyquinoxaline in 96% yield. (Hungarian Patent 152705 (1966) ; CA 65, 2275 f] . The method uses hydrogen peroxide which is very much hazardous. The second drawback is its reaction time that is very long. In the aerial oxidation method air is used to oxidise 2-ketotetrahydroquinoxaline into 2- hydroxyqui-noxaline. The oxidation reaction is carried out in methanolic potassium hydroxide at 45°C for 14 hours. [Indian Patent 149433 (1984), CA 97, 144877 p]. The drawback of the mehod is its reaction time which is very long. According to Potassium nitrosodium sulphonate oxidation method 2-ketotetrahydroquinoxaline is oxi-deized to 2- hydroxyquinoxaline in methanol using a buffer to maintain pH (yield 87%). [Chem Ber (1965) 98 (9), 2939- 53/CA-63, 18022f] The drawback of the method is that it involves use of costly chemicals such as potassium nitrosodisul phonate, copper oxide/chromic acid catalyst and the buffer solution. According to Chlorinated lime-oxidation method 2-ketotetrahydroquinoxaline is oxidized by chlorinated lime to give 2-hydroxy quinoxaline. The yield is 68% only. (Polish patent) - 76895 (1975); CA 85, 21454 w. The main objective of the present invention is to provide a simple process for the production of 2- hydroxoquinoxaline by the oxidation of 1,2,3,4- tetrahy-droquinoxaline -4-N-acetic acid which is a byproduct and is present always as an effluent in the process of the production of 2-ketotetrahydroquinoxaline prepared by the cyclo condensation of orthophenylene diamine and monochloro acetic acid at elevated temperatures. (Perkin, W.H. Jr. and Ritey, G.C.J. Chem. Soc. 1923, 123, 2599,. In this cyclo condensation reaction the conversion of o-phenylene diamine to 2- ketotetrahydro-quinoxaline is around 70% and the rest is distributed between unreacted starting material i.e. orthophenyle-nediamine and the byproduct 1,2,3,4- tetrahydro 2-ketoquinoxaJine -4 N- acetic acid, of the formula 4-Here, 2-ketotetrahydroquinoxaline of the formula 3, is converted to 2-hydroxyquinoxaline of the formula 5 and orthophenylene diamine of the formula 1 is recycled. The filtrate containing the acid of the formula 4. is either an effluent or removed as precipitate on acidification. The formation of acid of the formula 4 in this route is unavoidable. About 10-15% orthophenylen-diamine is converted into this N-acetic acid of the formula 4, which is quite high. The present invention provides a suitable method to generate 2-' hydroxyqui-noxaline of the formula 5 from the byproduct, N-acetic acid of the formula 4. The reactions are illustrated in Fig. 1 accompanying this specification. Accordingly, the present invention provides ah improved process for the preparation of 2-hydroxy qui-noxaline of the formula 5 shown in the drawing accompanying this specification which comprises adding water miscible polar solvent to 1, 2 , 3 , 4 - tetrahydro-2 -ketoquinoxaline-4N-acetic acid, of the formula 4 reacting the resulting mixture with an oxidising agent, stirring the reaction mixture, for a period in the range of 4-10 hours filtering and extracting the resultant product using a polar solvent which is not miscible with water by conventional methods, washing the solvent layer with water, drying, distilling the solvent under reduced pressure and crystallizing by known methods to obtain 2-hydroxy quinoxaline. The following examples are given by way of illus-tratation and should not be construed to limit the scope of the present invention. Example 1: To a solution of 5.15 gm (0.025 mole) of 1,2,3,4-tetrahydro-2-ketoquinoxaline -4-N-acetic acid (4) in methanol (120 ml) is added gradually 7.5 g(0,035 mole) sodium periodate solution in 40 ml water. The mixture is stirred at room temperature for 4 hours. Soon after the addition yellowish precipitate starts appearing and the mixture becomes quite thick. After the completion of the reaction, the solid is removed by filtration and the filtrate is extracted thoroughly with ethyl acetate. The organic layer is washed with water, dried over sodium sulphate and distilled under reduced pressure to give 3.5g residue which on crytallization from methanol gave 3.Og pale yellow coloured 2-hydroxy-quinoxaline m.p 269° C (Yield 82%). Example-2 To a solution of 4.12 gm (0.020 mole) of 1,2,3,4-tetrahydro 2-ketoquinoxaline-4N-acetic acid (4) in iso-propanol (100 ml) is added gradually aqueous sodium periodate solution (6.0 gm; 0.035 mole in 30 ml water). The mixture is stirred at room temperature for 5 hours. Soon after the addition, light brown precipitate starts appearing and the mixture becomes quite thick. After completion of the reaction, the solid is removed by filteration and the filtrate is extracted with water immicible organic sovents. The organic layer is washed with water, dried over sodium sulphate and distilled under reduced pressure to give 2-hydroxy-quinoxaline, yield 80.5% (m.p-269°C.) Example-3 To a solution of 5.15 gm (0.025 mole) of 1,2,3,4-tetrahydro-2-ketoquinoxaline -4-N-acetic acid (4) in ethanol (120 ml) is added gradually 7.5 g(0,035 mole) sodium periodate solution in 40 ml water. The mixture is stirred at room temperature for 4 hours. Soon after the addition yellowish precipitate starts appearing and the mixture becomes quite thick. After the completion of the reaction, the solid is removed by filtration and the filtrate is extracted thoroughly with ethyl acetate. The organic layer is washed with water, dried over sodium sulphate and distilled under reduced pressure to give 3.5g residue which on crytallization from methanol gave 3.Og pale yellow coloured 2-hydroxy-quinoxaline m.p 269° C (yield : 2.9 gms 80%). Example-4 To a solution of 5.15 gm (0.025 mole) of 1,2,3,4-tetrahydro-2-ketoquinoxaline -4-N-acetic acid (4) in n-butanol (130 ml) is added gradually 7.5 g(0,035 mole) sodium periodate solution in 40 ml water. The mixture is stirred at room temperature for 4 hours. Soon after the addition yellowish precipitate starts appearing and the mixture becomes quite thick. After the completion of the reaction, the solid is removed by filtration and the filtrate is extracted thoroughly with ethyl acetate. The organic layer is washed with water, dried over sodium sulphate and distilled under reduced pressure to give 3.5g residue which on crytallization from methanol gave 3.Og pale yellow coloured 2-hydroxy-quinoxaline m.p 269° C (Yield 2.85 gms 79%). The main advantqages of the present invention are: 1. The method is simple as it is done in aqueous alcoholic medium and at room temperature. 2. It provides a method to convert an effluent or by product into more useful product i.e, 2-hydroxy quinoxaline. 3 - It also provides a method to remove carboxymethyl group from the molecule in good yield. 4. This is a one-pot reaction. 5. The time of the reaction is not very long. 6. The oxidizing agent used in this process is also inexpensive and commercially available. We claim : 1. An improved process for the preparation of 2-hy droxy quinoxaline of the formula 5 shown in the drawing accompanying this specification which comprises adding water miscible polar solvent to 1,2,3,4-tetrahydro-2- ketoquinoxaline-4N-acetic acid, of the formula 4 react ing the resulting mixture with an oxidising agent, stirring the reaction mixture, for a period in the range of ■ 4-10 hours filtering and extracting the re sultant product using a polar solvent which is not miscible with water by conventional methods, washing the solvent layer with water, drying, distilling the solvent under reduced pressure and crystallizing by known methods to obtain 2-hydroxy quinoxaline. 2. An improved process as claimed in claim 1 wherein, the oxidising agent used is sodium, potasium or any salt of periodic acid. 3. An improved process as claimed in claim 1 & 2, wherein, the polar water miscible solvent used is selected from methanol, ethanol, propanol, iso-propanol and n-butanol. 4. An improved process as claimed in claims 1 to 3 wherein the polar and water immiscible solvent is used to extract the product is selected from ethylacetate, chloroform. 5. An improved process as claimed in claim 1 to 4 wherein the drying step is effected using a drying agent selected from sodium, magnesium, calcium or barium sulphate. 6. An improved process as claimed in claim 1 to 5 where in the distillation of organic solvent is effected at a temperature 20-50°C under reduced pressure. 7. An improved process as claimed in claim 1 to 6 wherein the crystallization is effected using polar solvents selected from methanol, ethanol acetonitrile and acetone. 8. An improved process for the preparation of 2- hydroxy quinoxaline of the formula 5 shown in the drawing accompanying the specification substantially as herein described with reference to the examples.

Documents:

1097-del-1995-abstract.pdf

1097-del-1995-claims.pdf

1097-del-1995-complete specification (granted).pdf

1097-del-1995-correspondence-others.pdf

1097-del-1995-correspondence-po.pdf

1097-del-1995-description (complete).pdf

1097-del-1995-drawings.pdf

1097-del-1995-form-1.pdf

1097-del-1995-form-2.pdf

1097-del-1995-form-4.pdf

1097-del-1995-form-5.pdf

1097-del-1995-form-6.pdf