Title of Invention

AN IMPROVED PROCESS FOR PREPARATION OF 3-AND 4-AMINOPHTHALIMIDE

Abstract

The invention discloses a simple, economical, and effluents-free process for the preparation of 3- and 4-aminophthalimide of formula-I, by reduction of the corresponding nitrophthalimides of formula-II under heterogeneous hydrogenation conditions using Pd, Pt, Ni catalysts at different temperature in the presence of polar solvent selected from diemthylformamide, dimethylacetamide, N-methyl-2-pyrrolidone in the presence or absence of alcoholic solvent. The 3- and 4-aminophthalimide of the formula-I prepared by the process of the present invention are useful as dyestuff intermediates. The compounds are suitable for use as fluorescent dyes for artificial fibers and natural vegetable and animal fibers. They are also useful as synthetic intermediates for the preparation of 5-bromophthalide, an intermediate for the preparation of citalopram.

Full Text

INTRODUCTION The present invention relates to an improved process for the preparation of 3- and 4-aminophthalimide. The 3- and 4-aminophthaUmide prepared by the process of the present invention has the formula-I given below: Basically, there are three approaches in the literature to make 3- and 4-aminophthalimide of the formula-I. In the first approach (J. Am. Chem. See, 1908, 30, 1135), dimethyl- or method of this approach (J. Chem. Soc, 1931, p79; Crompt. Rend., 1937, 205, 989; Bull. Soc. Chim., 1939, 6, 478; Chem. Abstr., 52, 6361, 1958; Ann. Pharm. France, 1958, 16, 21; Chem. Abstr., 77, 19330u, 1972; US patent no. 2,436,362) more than four equivalents of stannous chloride dihydrate is used and the reduction is done in large quantity of cone, hydrochloric acid medium. The main disadvantage of this process is, the requirement of a large quantity of stannous chloride dihydrate and cone, hydrochloric acid for the reduction. This is a serious environmental problem as a large quantity of acidic stannic effluents are produced in this process. Also, the cost of stannous chloride is not suitable for an effective economic commercial process. In the second process (US patent No. 3397187) of the second approach, sodiimi hydrosufite is used as a reducing agent. By using this reagent only one compound (4-aminophthalimide) is prepared and the yield reported is 49%. The main drawback in this process is again the requirement of a large quantity of sodium hydrosulfite. Further, the process requires purification of the resulting compound by repeated leaching and crystallization technique. effluents generated from the above-mentioned processes and cost involved in making these compounds. We observed that a promising approach for development of such a process is to (a) avoid the usage of costly and polluting reagents like, stannous chloride (b) minimize the effluents like large quantities of hydrochloric acid or stannous chloride (c) develop a process where reagents used in the process can be recovered and reused (d) develop a process where by-products are of environment friendly, and (e) raw material used in the process should be readily available. The present invention has been developed based on our observation that 3- and 4-nitrophthalimide of the formula-II could be the starting material of choice as they are readily and cheaply available on a commercial scale. Also, reduction of the nitro group (present in 3- or 4-nitophthalimides of the formula-II) can be done employing metals like Pd, Pt, Ni under heterogeneous hydrogenation conditions. The common solvents used in such hydrogenation conditions are alcohols like methanol, ethanol, iso-propanol; esters like ethyl acetate, acids like acetic acid, etc. Surprisingly, both 3- and 4-nitrophthalimides of the formula-II do not have good solubility in these solvents making them difficult to reduce under heterogeneous hydrogenation conditions. During our sustained research to develop a simple process for the reduction of 3- and 4-nitrophthalimide of the formula-II, we observed that a promising approach for such process would be to: i) Select a proper solvent for the hydrogenation of 3- and 4-nitrophthalimide of the formula-II where both starting material and the product have good solubility, ii) Select a proper solvent, which can be recovered and reused, iii) Select a proper hydrogenation catalyst, which is cheap and recyclable. During our preliminary studies we found that 3- and 4-nitrophthalimide of the formula-II have good solubility in dimethylformamide, dimethylacetamide, N-methyl-2-pyrrolidone alone or in combination with alcoholic solvents. Based on this observation we studied the hydrogenation of 3- and 4- nitrophthalimide of the formula-II using these solvents. Accordingly the present invention provides an improved process for the preparation of 3-and 4-aminophthalimide of the formula-I 0 NH O I which comprises: (i) dissolution of 3- and 4-nitrophthalimide of the formula-II O O-N-f NH O II in a polar solvent selected from diemthylformamide, dimethylacetamide, N- methyl-2-pyrrolidone and in the presence or absence of an alcoholic solvent or its mixture (ii) charging of a hydrogenation catalyst to the resulting solution (iii) reducing the nitro compound under hydrogen pressure at a temperature in the range of 25 to 80°C (iv) filtering the catalyst after the completion of hydrogenation reaction (v) distilling off the solvent used in the hydrogenation step under vaccum (vi) isolating the 3- and 4-aminophthalimide of the formula-I formed by suspending the residue in water and filtration. The alcoholic solvents employed may be selected from methanol, ethanol, isopropyl alcohol, etc. The catalyst used in step (ii) may be selected from Pd/C, Raney nickel, Rh/C, Ru/C, etc. The hydrogen pressure used in step (iii) may be in the range of 10-60psi and the temperature employed may be preferably in the range of 20 tolOO°C. The solvent distillation temperature in step (v) may be in the range of 40-100°C. This simplification of the process has led to the synthesis of 3-and 4-aminophthalimide of the formula-I with no polluting effluents. Also, the catalyst as well as the solvent used in the process could be recycled thereby making the process cheap. The by-product produced in the process is only water thereby making it an eco-friendly process. The invention is described in detail in the examples given below which are provided only by way of illustration and therefore should not be construed to limit the scope of the invention. EXAMPLE 1 Preparation of 3-aminophthalimide from 3-nitrophthalimide: Using dimethylformamide as solvent and Raney nickel as catalyst: 3-Nitrophthalimide (lOOgr) was taken into a hydrogenation vessel and dissolved using 500ml of dimethylformamide. Raney nickel catalyst (20gr, wet) was added to the solution and subjected to hydrogenation conditions initially at 20-30°C under 20-40psi. After the exothermic nature of the reaction was over, hydrogen pressure was increased to 40-60psi and the temperature to 40-50°C. After the hydrogen uptake is over sample was drawn from the reaction mass and checked for the absence of 3-nitrophthalimide by TLC. The reaction mixture was filtered while hot and the catalyst removed by filtration. Solvent was removed from the filtrate under reduced pressure at 60-80°C. Water (500ml) was added to the residue and the mixture stirred for 20-30min. The product was isolated by filtration and dried at 60-70°C to get a yellow crystalline solid of 3-aminophthalimide (80gr, 95%). Melting point: 262-4°C. EXAMPLE 2 Using dimethylformamide/methanol as solvent and Raney nickel as catalyst: 3-Nitrophthalimide (lOOgr) was taken into a beaker and dissolved using 200ml of dimethylformamide and 300ml of methanol. The solution was transferred into a IL hydrogenation kettle and 20gr of Raney nickel was charged into the kettle. Hydrogenation was carried out initially at 20-40psi and 25-30°C until the exothermic nature was over. Hydrogenation was further continued at 40-60psi pressure and 40-50°C. After checking the completion of reaction by TLC catalyst was removed by filtration and the solvents distilled off from the reaction mixture at 50-60°C. The residue thus obtained was suspended in water (500ml) and filtered off to get a bright yellow crystalline compound of 3-aminophthaIiniide (78gr, 92.5%). Melting point; 263-4°C EXAMPLE 3 Using dimethylformamide as solvent and 5% Pd/C as catalyst: 3-Nitrophthalimide (lOOgr) was taken into a hydrogenation kettle and dissolved using 500ml of dimethylformamide. 5% Palladium/carbon (lOgr, 50% wet) was added to the solution and subjected to hydrogenation conditions initially at 20-30°C under 20-40psi. After the exothermic nature of the reaction was over, hydrogen pressure was increased to 40-60psi and the temperature to 40-50°C. After the hydrogen uptake was over the reaction mixture was filtered while hot and the catalyst removed by filtration. Solvent was removed from the filtrate under reduced pressure at 60-80°C. Water (500ml) was added to the residue and the mixture stirred for 30min. The product was isolated by filtration and dried at 60-70°C to get SOgr (95%) of yellow crystalline solid of 3-aminophthalimide. Melting point: 263-4°C. EXAMPLE 4 Preparation of 4-aniinophthalimide from 4-nitrophthalimide: Using diemthylformamide as solvent and Raney nickel as catalyst: 4-Nitrophthalimide (lOOgr) was taken into a hydrogenation vessel and dissolved using 600ml of dimethylformamide. Raney nickel catalyst (20gr, wet) was added to the solution and hydrogenated initially at 20-3 0°C under 20-40psi pressure. After the exothermic nature of the reaction was over, hydrogen pressure was increased to 40-60psi and the temperature to 40-50°C. After the hydrogenation is over the reaction mixture was filtered while hot and the catalyst removed by filtration. Dimethylformamide was removed from the filtrate under reduced pressure at 60-80°C. Water (500ml) was added to the residue and the mixture stirred for 20-30min. The product was isolated by filtration and dried at 60-70°C to get a yellow crystalline solid of 4-aminophthaIiniide (82gr, 97%). Melting point: 293-5°C. EXAMPLE 5 Using dimethylformamide/methanol as solvent and Raney nickel as catalyst: 4-Nitrophthalimide (lOOgr) was taken into a beaker and dissolved using 300ml of dimethylformamide and 400ml of methanol. The solution was transferred into a IL hydrogenation kettle and 20gr of wet Raney nickel catalyst was charged into the kettle. Hydrogenation was carried out initially at 20-40psi and 25-30°C until the exothermic nature was over. Hydrogenation was further continued at 40-60psi pressure and 40-50°C. After checking the completion of reaction by TLC, catalyst was removed by filtration and the solvents distilled off from the reaction mixture at 50-60°C. The residue thus obtained was suspended in water (500ml) and filtered off to get a bright yellow crystalline compound of 4-aniinophthalimide (78gr, 92.5%). Melting point: 294-5°C. EXAMPLE 6 Using dimethylformamide as solvent and 5% Pd/C as catalyst: 4-Nitrophthalimide (lOOgr) was taken into a hydrogenation kettle and dissolved using 700ml of dimethylformamide. 5% Palladium/carbon (lOgr, 50% wet) was added to the solution and hydrogenated initially at 20-30°C under 20-40psi. After the exothermic nature of the reaction was over, hydrogen pressure was increased to 40-60psi and the temperature to 40-50°C. After the hydrogenation was over the reaction mixture was filtered while hot and the catalyst removed by filtration. Dimethylformamide was removed from the filtrate under reduced pressure at 60-80°C. Water (500ml) was added to the residue and the mixture stirred for SOmin. The product was isolated by filtration and dried at 60-70°C to get 80gr (95%) of yellow crystalline solid of 4-aminophthalimide. Mehing point: 294-5°C. The main advantages of the present invention are: (i) The process is convenient for preparing the compounds of the formula-I for any scale of production, (ii) Both the solvent and the catalyst used in the reaction can be recycled to any number of times thereby making the process economical, (iii) Effluents produced in the process are negligible. By-product in the process is only water thereby making the process eco-friendly. (iv) Process is economically commercially viable, (v) The process does not involve any costly or polluting reagents. We Claim: 1. An improved process for the preparation of 3- and 4-aminophthalimide of formula-I, in a polar solvent selected from diemthylformamide, dimethylacetamide, N- methyl-2-pyrrolidone and in the presence or absence of an alcoholic solvent or its mixture (ii) charging of a hydrogenation catalyst to the resulting solution (iii) reducing the nitro compound under hydrogen pressure at a temperature in the range of 20tol00°C (iv) filtering off the catalyst after the completion of hydrogenation reaction (v) distilling off the solvent used in the hydrogenation step under vaccum and (vi) isolating the 3 -and 4-aminophthalimide of the formula-I formed by suspending the residue in water and filtration. 2. An improved process as claimed in claim 1 wherein the alcoholic solvent used is selected from methanol, ethanol, iso-propanol, etc, preferably methanol. 3. An improved process as claimed in claims 1 & 2 wherein the catalyst used in the hydrogenation step is 5% to 10% Pd/C, Pt/C, Rh/C, Ru/C, Raney nickel, etc, preferably Raney nickel or 5% Pd/C. 4. An improved process as claimed in claims 1 to 3 wherein the temperature of the reaction is in the range of 20-100°C, preferably in the range of 20-60°C. 5. An improved process as claimed in claims 1 to 4 wherein the hydrogenation pressure used is in the range of 10-80psi, preferably in the range of 20-60psi. 6. An improved process as claimed in claims 1 to 5 wherein the solvent distillation is effected at a temperature in the range of 60-150°C, preferably in therangeof60-100'C. 7. An improved process for the preparation of 3-and 4-aminophthalimide of formula-I substantially as herein described with reference to the Example 1-6.

Documents:

0829-mas-2002 abstract-duplicate.pdf

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0829-mas-2002 abstract.pdf

0829-mas-2002 claims-duplicate.pdf

0829-mas-2002 claims.pdf

0829-mas-2002 correspondence-others.pdf

0829-mas-2002 correspondence-po.pdf

0829-mas-2002 description(complete)-duplicate.pdf

0829-mas-2002 description(complete).pdf

0829-mas-2002 form-1.pdf

0829-mas-2002 form-19.pdf

0829-mas-2002 form-3.pdf