Title of Invention

METHOD FOR PREPARING 4-AMINODIPHENYLAMINE

Abstract

The present invention relates to a method for preparing 4-aminodiphenylamine comprising the steps of reacting carbanilide and nitrobenzene in an adequate solvent in the presence of an appropriate organic base or a mixture of an organic base and an inorganic base and subsequently reducing the reaction product, or a 4-aminodiphenylamine intermediate, without separation from the reaction mixture, in the presence of an appropriate catalyst and hydrogen gas. Because the method of the present invention uses carbanilide as starting material, which reacts directly with nitrobenzene with high reactivity and selectivity, generation of by-products such as phenazine and 2-nitrodiphenylamine can be reduced and the 4-aminodiphenylamine intermediate can be prepared with good selectivity and production yield. Also, because a recyclable organic base is used, amount of wasted material can be minimized and 4-aminodiphenylamine, or the final product, can be prepared efficiently, without the separation of 4-aminodiphenylamine intermediate for the subsequent reduction process. In addition, in comparison with conventional preparation methods of 4-aminodiphenylamine, generation of harmful wastes can be significantly reduced and environment-damaging corrosive materials are not generated.

Full Text

Description METHOD FOR PREPARING 4-AMINODIPHENYLAMINE Technical Field [1] The present invention relates to a method for preparing 4-aminodiphenylamine (hereunder referred to as "4- ADPA") from carbanilide and nitrobenzene. More particularly, it relates to a method for preparing 4- ADPA comprising the steps of reacting carbanilide and nitrobenzene in the presence of an appropriate organic base or a mixture of an organic base and an inorganic base to prepare 4-nitrodiphenylamine (hereunder referred to as "4-NDPA") and 4-nitrosodiphenylamine (hereunder referred to as "4-NODPA") with good selectivity and yield and continuously reducing them with an appropriate catalyst and hydrogen without a separation process. Background Art [2] In general, 4- ADPA is widely used to prepare 6PPD(N-(1, 3-dimethylbutyl)-N'- phenyl-/?-phenylenediamine), IPPD (N-isopropyl-N-phenyl-p-phenylenediamine), etc. by reductive alkylation, which are utilized as anti-aging agent of rubber. [3] The known industrial preparation processes of 4- ADPA can be classified into three groups. They are the Monsanto process, the Ouchi process and the NASH (nucleophilic aromatic substitution for hydrogen) process. [4] In the Monsanto process, chlorobenzene is nitrated top-chloronitrobenzene, and then reacted with formanilide to prepare 4-NDPA. Then, 4-NDPA is hydrogenated to prepare 4- ADPA. In this preparation method, treatment of corrosive wastewater containing chlorine and a large amount of organic and inorganic waste liquids are required. [5] In the Ouchi process, diphenylamine is reacted with sodium nitrite (NaNO2) to prepare N-nitrosodiphenylamine, which undergoes Fischer-Hepp rearrangement, neutralized and then hydrogenated to prepare 4- ADPA. This process has the problem of generation of a lot of harmful waste liquid during the nitrosation process. [6] The third process, or the NASH process, has been proposed as an alternative to the processes generating harmful materials. [7] One of the NASH process is the process of directly reacting aniline and nitrobenzene in the presence of base such as tetramethylammonium hydroxide (hereunder referred to as "TMAH") to prepare 4-NDPA and 4-NODPA (J. Am. Chem. Soc, 1992, 114(23), 9237-8; USP No. 5,117,063; USP No. 5,252,737; USP No. 5,331,099; USP No. 5,453,541; USP No. 5,552,531; USP No. 5,633,407). This process is advantageous in reducing the amount of waste and environmentally harmful materials. [8] However, this method is disadvantageous in that excessive byproducts, such as 2- nitrodiphenylamine (hereunder referred to as "2-NDPA"), phenazine and azobenzene, are generated because aniline tends to react at ortho site of nitrobenzene. [9] Other proposed methods of preparing 4- ADPA include head-to-tail addition of aniline (USP No. 4,760,186) and hydrogenation ofp-nitrosodiphenylhydroxylamine. However, these methods are disadvantageous in production efficiency and in economic aspect. As a new preparing method using the NASH reaction process to prepare 4- ADPA, reaction of aniline and azobenzene in the presence of base such as TMAH (J. Org. Chem., 1994, 59(19), 5627-5632; USPNos. 5,382,691 and 5,618,979, EP No. 726,889, WO No. 95/12569, JP No. 9504546) is also known. But, this method is also disadvantageous in production yield. [10] As another method of using the NASH reaction and using anilide as starting material, a method of reacting acetanilide and nitrobenzene in a DMSO solvent in the presence of NaOH and K.2CO3 to prepare 4-NODPA is known (Tetrahedron Letters, vol. 31, No. 22, pp 3217-3210, 1990). However, the acetanilide is unstable under the reaction condition and by-products are generated by the decomposition of starting. [11] As another method of using the NASH reaction, a method of reacting carbanilide and nitrobenzene in a dimethylsulfoxide (hereunder referred to as "DMSO") solvent in the presence of NaOH, an inorganic base, to prepare 4-NDPA is known. (USP No. 5,684,203, WO No. 0051966). This method requires recycle of the inorganic base and use of the expensive DMSO solvent. Besides, the removal of DMSO solvent is required prior to hydrogenation to avoid possible poisoning of precious metal catalyst. Disclosure of Invention Technical Problem [12] Thus, it is an object of the present invention to solve the problem of difficulty in continuous hydrogenation with regard to use of DMSO and an inorganic base for the reaction of carbanilide and nitrobenzene and provide an economical method for preparing 4- ADPA by continuously hydrogenating 4-NDPA and 4-NODPA, which are intermediates in the preparation of 4- ADPA, in the presence of a reactive organic base or a mixture of organic base and inorganic base. [13] It is another object of the invention to provide a method for preparing 4- ADPA offering reduced reaction time and capable of reducing by product generation by employing highly reactive and selective carbanilide as starting material instead of aniline and reacting it with nitrobenzene. [14] It is still another object of the invention to provide a method for preparing 4- ADPA capable of reducing amount of wastes without affecting continuous hydrogenation using a recyclable organic base, such as TMAH, with good reactivity in a common organic solvent instead of alkali metal or alkaline earth metal bases requiring such expensive organic solvents as DMSO and hexamethylphosphoramide (hereunder referred to as "HMPA"). Best Mode for Carrying Out the Invention [15] The present invention relates to a method for preparing 4- ADPA from carbanilide and nitrobenzene. More particularly, it relates to a method for preparing 4-ADPA comprising the steps of reacting carbanilide and nitrobenzene in the presence of an appropriate organic base or a mixture of an organic base and an inorganic base to prepare 4-NDPA and 4-NODPA with good selectivity and yield and continuously reducing them with an appropriate catalyst and hydrogen without a separation process. [16] More specifically, the present invention is advantageous in that 4-NDPA and 4- NODPA can be selectively obtained in good yield using carbanilide, which can be easily prepared from urea and aniline, as starting material and using a recyclable organic base. Because recycling of the organic base is maximized, generation of wastewater can be significantly reduced. Reaction solution containing 4-NDPA and 4-NODPA may be hydrogenated with an adequate catalyst, for example, Pt/C or Pd/C, without separation. Alternatively, TMAH, or the organic base, may be removed from the aqueous phase of the reaction solution and then organic phase may be hydrogenated to obtain 4- ADPA. After hydrogenation, the solvent and aniline included in the reaction solution are removed by vacuum distillation, and then azobenzene and phenazine byproducts are removed to obtain coarse 4- ADPA residual. Finally, the coarse 4- ADPA is purified under a high temperature, vacuum distillation condition to obtain pure 4- ADPA. [17] The conventional reaction of aniline and nitrobenzene has the problem of separating 4-NDPA and 4-NODPA because of the 2-NDPA and phenazine byproducts generated by ortho attack. When carbanilide is used as starting material, the steric hindrance caused by the amide structure greatly reduces byproduct formation due to the ortho attack. [18] The present invention is advantageous in that amount of waste can be minimized because the organic base is recyclable, corrosion of reactor can be prevented because no corrosive wastewater containing chlorine is generated and reaction time decreases and production yield of 4-NDPA and 4-NODPA increases because highly reactive carbanilide is used. [19] In the preparing method of the present invention, an solvent not affecting the NASH reaction is used. For example, toluene, benzene, N-methyl-2-pyrrolidinone (hereunder referred to as "NMP"), tetrahydrofuran (hereunder referred to as "THF"), dioxane, ethylene glycol dimethyl ether and nitrobenzene may be used alone or in combination. However, these solvents are not limiting examples. Preferably, nitrobenzene is used as reactant and at the same time as solvent since it affects neither the NASH reaction nor the continuous hydrogenation. Also, it is preferable to use toluene or benzene, which can effectively remove water generated during the reaction. [20] When selecting the solvent, it is important to select one not affecting catalyst activation during the continuous hydrogenation and capable of effectively separating the organic base from the aqueous phase. For example, nitrobenzene, toluene, nitrobenzene or ethylene glycol dimethyl ether is preferable. The proportion of the solvent to carbanilide is 1-50 to 1, preferably 3-30 to 1, based on weight. [21 ] For the base, an organic base easy to collect and recycle after reaction may be used alone or in combination with an alkali metal inorganic base. The organic base may be, for example, tetraalkylammonium hydroxides or alkyl- substituted diammonium hydroxides. For the tetraalkylammonium hydroxides, tetramethylammonium hydroxide (TMAH) or one generating TMAH is more preferable. The inorganic base may be sodium hydroxide (NaOH), sodium hydride, potassium hydroxide (KOH), calcium hydroxide, calcium hydride or a mixture thereof. These inorganic bases are used along with the organic base as supplementary. Along with the organic base or the mixture base, crown ether or a tetraalkylammonium salt like tetraalkylammonium chloride may be used as phase transfer catalyst. Preferably, the mixture base comprises 30-90 mol% of organic base and 10-70 mol% of inorganic base. If the content of inorganic base is larger, recycling of the base is difficult and reactivity decreases. [22] The base is used in 1-10, preferably 2-5, molar equivalents of carbanilide. If the content of the base is larger, formation of byproducts, such as azobenzene, azoxybenzene and phenazine, increases. Otherwise, if it is smaller, reactivity may decrease. [23] Nitrobenzene is used in 1-30, preferably 3-10, molar equivalents of carbanilide. As the content of nitrobenzene increases, reaction rate and production yield per given time increase. However, if the content of nitrobenzene is too large, azoxybenzene is generated as byproduct, thereby reducing selectivity of 4-NDPA. [24] Reaction temperature is preferably 0-150 °C, more preferably 50-80 °C. If the reaction temperature is lower, reaction rate decreases. Otherwise, if it exceeds 150 °C, generation of byproducts increases, so that production yield of 4-NDPA and 4-NODPA decreases. [25] Water generated during reaction may be removed by vacuum distillation or using a drying agent in order to improve production yield. Anhydrous potassium carbonate, anhydrous sodium sulfate, anhydrous magnesium sulfate, sodium hydroxide, potassium hydroxide, sodium hydride or a molecular sieve may be used as the drying agent. [26] Preferably, the reaction is performed at normal pressure under nitrogen or oxygen atmosphere, or in vacuum. Under nitrogen atmosphere, such byproducts as azobenzene and azoxybenzene are generated, but generation of azoxybenzene is minimized under oxygen or air atmosphere. However, it is not necessary to define the reaction atmosphere severely, because azobenzene and azoxybenzene can be easily converted into aniline by hydrogenation for recycling. [27] Analysis of reactants and products was performed with nuclear a magnetic resonance (NMR) spectrometer and a gas chromatography-mass spectrometer detector (GC-MSD). Quantitative analysis was performed by high performance liquid chromatography (hereunder referred to as "HPLC") and gas chromatography (hereunder referred to as "GC"). [28] HPLC analysis condition for measuring carbanilide conversion ratio and yield of 4-NDPA and 4-NODPA was as follows. HPLC column: Waters 5C18-AR-II (4.6 x!50 mm); Solvent condition: [29] (Table Removed) [30] GC analysis condition for quantitative analysis of 4- ADPA prepared from the NASH reaction of carbanilide and nitrobenzene and subsequent hydrogenation was as follows. [31 ] Capillary column: ULTRA 2 (Crosslinked 5% Ph Me Silicon) [32] 50 m xO.2 mm xO.33 urn [33] Carrier gas: Nitrogen [34] Head pressure: 18 psig [35] Oven: 100 °C (2 min) to 280 °C, p= 10 °C/min [36] Detector (temperature): FID (280 °C) [37] Split ratio: 50:1 [38] Carrier gas flow-rate: 38 mL [39] For the quantitative analysis of each product, pyrene was used as an internal standard substance. Also, the factors of gas chromatography on each product were applied to its area rate before analysis so as to calculate the molar ratio (mole %) of each product on the basis of initially added carbanilide. [40] Hereunder are given examples of preparing 4-NDPA and 4-NODPA intermediates and 4- ADPA. The following examples are only for the understanding of the present invention and not to be construed as limit the scope thereof. [41] EXAMPLES [42] Experimental Example 1 [43] 12.7 g (60 mmole) of carbanilide and 36.9 g (300 mmole) of nitrobenzene were put in a 200 mL, 3-necked round bottom flask equipped with a cooler and a stirrer. After heating the flask to 80 °C, 23.9 g (132 mmole) of TMA(OH)'52HO was added.Reaction was performed for 3 hours while keeping the degree of vacuum at about 90-50 mmHg and distilling water. [44] 500 mg of pyrene was added as internal standard at the early step of the reaction (This procedure was applied to all experimental examples and examples). [45] [46] [47] [48] [49] [50] [51] [52] Ethyl acetate was added to the reaction solution. The solution was neutralized with water and acetic acid. The ethyl acetate layer was separated and analyzed by HPLC. Conversion ratio of carbanilide was 99 %. Production yield was 90 mole% 4-NDPA and 8 mole% 4-NODPA, based on carbanilide. Byproducts were 8 mole% phenazine, 9 mole% azobenzene and 27 mole% azoxybenzene, based on carbanilide. Experimental Example 2 Production yield of 4-NDPA and 4-NODPA was compared for various nitrobenzene contents. 12.7 g (60 mmole) of carbanilide and 4-10 molar equivalents of nitrobenzene were put in a 200 mL, 3-necked round bottom flask equipped with a cooler and a stirrer. After heating the flask to 80 °C, 21.7 g (120 mmole) of TMA(OH)'5H2O was added. Reaction was performed for 3 hours while keeping the degree of vacuum at about 90-50 mmHg and distilling water. Ethyl acetate was added to the reaction solution. The solution was neutralized with water and acetic acid. The ethyl acetate layer was separated and analyzed by HPLC. The result is given in Table 1. (Table Removed) [53] [54] [55]Experimental Example 3 Production yield of 4-NDPA and 4-NODPA was compared for various base contents. 12.7 g (60 mmole) of carbanilide and 36.9 g (300 mmole) of nitrobenzene were put in a 200 mL, 3-necked round bottom flask equipped with a cooler and a stirrer. After heating the flask to 80 °C, 21.7 g (120 mmole) of TMA(OH)'5H2O was added. [56] [57] [58] [59] [60] [61] [62] [63]Reaction was performed for 3 hours while keeping the degree of vacuum at about 90-50 mmHg and distilling water. Ethyl acetate was added to the reaction solution. The solution was neutralized with water and acetic acid. The ethyl acetate layer was separated and analyzed by HPLC. Conversion ratio of carbanilide was 92 %. Production yield was 84 mole% 4-NDPA and 8 mole% 4-NODPA, based on carbanilide. Byproducts were 4 mole% phenazine, 7 mole% azobenzene and 25 mole% azoxybenzene, based on carbanilide. Experimental Example 4 Production yield of 4-NDPA and 4-NODPA was compared for various reaction temperatures. 6.4 g (30mmole) of carbanilide and 36.9 g (300 mmole) of nitrobenzene were put in a 200 mL, 3-necked round bottom flask equipped with a cooler and a stirrer. Varying temperature, 10.9 g (60 mmole) of TMA(OH)'5H2O was added. Reaction was performed for 3 hours while keeping the degree of vacuum at about 90-50 mmHg and distilling water. Ethyl acetate was added to the reaction solution. The solution was neutralized with water and acetic acid. The ethyl acetate layer was separated and analyzed by HPLC. The result is given in Table 2. Table 2 [64] [65] [66] (Table Removed) Production yield of 4-NDPA and 4-NODPA was compared for various mixture bases including TMA(OH)'5H2O and inorganic bases. 6.4 g (30mmole) of carbanilide and 36.9 g (300 mmole) of nitrobenzene were put in a 200 mL, 3-necked round bottom flask equipped with a cooler and a stirrer. After heating the flask to 80 °C, 10.9 g (60 mmole) of TMA(OH)'5H2O was added. [67] [68] [69] Reaction was performed for 3 hours while keeping the degree of vacuum at about 90-50 mmHg and distilling water. Ethyl acetate was added to the reaction solution. The solution was neutralized with water and acetic acid. The ethyl acetate layer was separated and analyzed by HPLC. The result is given in Table 3. Table 3 (Table Removed) [70] [71] [72] [73] [74] Experimental Example 6 Production yield of 4-NDPA and 4-NODPA was compared for various solvents. 12.7 g (60 mmole) of carbanilide and 36.9 g (300 mmole) of nitrobenzene were put in a 200 mL, 3-necked round bottom flask equipped with a cooler and a stirrer. 64 mL of reaction solvent was added to the flask. After heating the flask to 80 °C, 21.7 g (120 mmole) of TMA(OH)'5H2O was added. Reaction was performed for 3 hours while varying reaction conditions. Ethyl acetate was added to the reaction solution. The solution was neutralized with water and acetic acid. The ethyl acetate layer was separated and analyzed by HPLC. The result is given in Table 4. [75] Table 4 (Table Removed) [76] [77] [78]Example 1 4- ADPA was prepared from the reaction solution including 4-NDPA and 4-NODPA by hydrogenation without a separation process. 12.7 g (60 mmole) of carbanilide and 36.9 g (300 mmole) of nitrobenzene were put in a 200 mL, 3-necked round bottom flask equipped with a cooler and a stirrer. After heating the flask to 80 °C, 23.9 g (132 mmole) of TMA(OH)'5H2O was added. Reaction was performed for 3 hours while keeping the degree of vacuum at about 90-50 mmHg and distilling water. 100 mL and toluene and 20 mL of water were added to the reaction solution. The water phase was separated and the organic phase containing the product was added to a high-pressure reactor. 0.3 g of 5% Pd/C (dry) was added to the reactor and air inside the reactor was substituted by hydrogen. Reaction was performed for 1 hour while keeping the reaction temperature at 80 °C and the hydrogen pressure at 15 kg/cm2. Conversion ratio of 4-NDPA and 4-NODPA was 100 % and production yield of 4- ADPA was 90 %. A method for preparing 4-aminodiphenylamine comprising the steps of reacting carbanilide and nitrobenzene in an adequate organic solvent system in the presence of an organic base or a mixed base of organic base and inorganic base and hydrogenating the resulted products without separation process. Industrial Applicability [79] As described above, the method of the present invention enables preparation of a 4-aminodiphenylamine intermediate with good selectivity and yield while reducing generation of such byproducts as phenazine and 2-nitrodiphenylamine by directly reacting highly reactive and selective carbanilide with nitrobenzene. It also minimizes generation of wastes because it uses a recyclable organic base. The 4-aminodiphenylamine intermediate may be continuously reduced to prepare 4-aminodiphenylamine, or the target product, in good yield without a separation process. The method of the present invention significantly reduces the amount of harmful wastes, differently from the conventional preparation methods, and generates no environment-damaging corrosive materials. We claim: [1] A method of preparing 4-aminodiphenylamine comprising the steps of reaction carbanilide and nitrobenzene in an adequate organic solvent system in the presence of an organic base or a mixed base of organic base and inorganic base and hydrogenating the resulted products without separation process, wherein the mole ratio of the carbanilide, the nitrobenzene and the base is 1:1-30:1-10. [2] The method as claimed in claim 1, wherein the organic base is tetraalkylammonium hydroxide or alkyl-substituted diammonium hydroxide. [3] The method as claimed in claim 2, wherein the tetraalkylammonium hydroxide is tetram- ethylammonium hydroxide. [4] The method as claimed in claim 1, wherein the inorganic base is at least one selected from the group consisting of sodium hydroxide, sodium hydride, potassium hydroxide, calcium hydroxide and calcium hydride. [5] The method as claimed in claim 1, wherein the mixed base comprises 30-90 mol% of organic base and 10-70 mol% of inorganic base. [6] The method as claimed in claim any one of claims 2 to 4, wherein the said method employs a phase transfer catalyst selected from the group consisting of crown ether and a tetraalkylammonium salt. [7] The method as claimed in claim 1, wherein the solvent is at least one selected from the group consisting of toluene, benzene, N-ethyl-2-pyrrolidinone, nitrobenzene, tetrahydrofuran, dioxane and ethylene glycol dimethyl ether. [8] The method as claimed in claim 1, wherein water generated during the reaction is removed under reduced pressure or using such a drying agent as anhydrous potassium carbonate, anhydrous sodium sulfate, anhydrous magnesium sulfate, sodium hydroxide, potassium hydroxide, sodium hydride and a molecular sieve. [9] The method as claimed in claim 1, wherein nitrobenzene is used in 1-30 molar equivalents per 1 mole of carbanilide. [10] The method as claimed in claim 1, wherein the weight ratio of solvent to carbanilide is 1-50. [11] The method as claimed in claim 1, wherein the reaction of carbanilide and nitrobenzene is performed at 0-150 °C. [12] The method as claimed in claim 1, wherein the reaction of carbanilide and nitrobenzene is performed under nitrogen or oxygen atmosphere or in vacuum. [13] The method as claimed in claim 1, wherein the hydrogenation is performed by using hydrogen in the presence of an adequate catalyst.

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9218-delnp-2007-abstract.pdf

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