WO2000051966A1

WO2000051966A1 - The method for preparing 4-nitrodiphenylamine from carbanilide

Info

Publication number: WO2000051966A1
Application number: PCT/KR1999/000738
Authority: WO
Inventors: Young J. Joo; Jin-Eok Kim; Kum-Ui Hwang; Jee-Yun Lee
Original assignee: Korea Kumho Petrochemical Co., Ltd.
Priority date: 1999-03-04
Filing date: 1999-12-04
Publication date: 2000-09-08
Also published as: KR20000059541A; AU1513700A; CN1266052A; JP2000256282A; KR100283374B1

Abstract

Disclosed herein is a process for preparing 4-nitrodiphenylamine using a nucleophilic aromatic substitution for hydrogen, comprising reacting carbanilide and nitrobenzene in a polar organic solvent in the presence of a base and a drying agent at a temperature of from 20 °C to 150 °C. This process is advantageous in that relatively cheap alkaline salts are used, and 4-nitrodiphenylamine can be produced at high selectivity and conversion without generating the environmentally hazardous corrosive reaction byproduct.

Description

THE METHOD FOR PREPARING 4-NITRODIPHENYLAMINE FROM CARBANILIDE

Technical Field

The present invention relates to a process for the preparation of 4-nitrodiphenylamine (hereinafter, called "4-NDPA") at a high selectivity and conversion by reacting carbanilide with nitrobenzene in the presence of a base such as, for example, sodium hydroxide, and a polar organic solvent. 4-Nitrodiphenylamine prepared according to this invention is used as the raw material for preparing 4-amino diphenylamine (hereinafter, called "4- ADPA"), which is an intermediate to an antioxidant, by conventional hydrogenation.

Background Art

Processes for preparing currently commercialized 4- ADPA can be largely classified into two processes: First, a Monsanto process is a process in which chlorobenzene is subjected to nitration to obtain p-chloronitrobenzene which is then reacted with formanilide. The resultant product is then hydrogenated by conventional manner to produce the 4-ADPA. This process, however, has a problem in that a corrosive waste water generated, such as by chlorine, during the reaction , and an amount of organic and inorganic waste liquids need to be disposed of at a considerable expense. Second, an Ouchi process is mentioned. In such an Ouchi process, the reaction of diphenylamine with sodium nitrite produces N- nitrosodiphenylamine which is then subjected to Fischer- Hepp Rearrangement. After that, the resultant product is neutralized and then hydrogenated in conventional manner to produce the 4-ADPA. However, a problem with the latter process is that an amount of hazardous waste liquid is caused due to nitrosation.

Besides the above processes, it is known to prepare 4-ADPA by either the head-to-tail coupling of aniline (see, USP No. 4,760,186) or the hydrogenation of p- nitrosodiphenylhydroxylamine. However, these processes have a problem in that they are uneconomical and provide the 4-ADPA at low yield. In recent years, processes using the nucleophilic aromatic substitution for hydrogen have been proposed as alternatives to the prior art processes involving the generation of the problematic hazardous material. Among these processes is one preparing the 4-NDPA and 4- nitrosodiphenylamine by the direct reaction of aniline with nitrobenzene in the presence of a base such as tetramethylammonium hydroxide (hereinafter, called "TMA(OH)"). According to these alternative processes, the amount of the waste material generated was reduced remarkably, and the generation of the environmentally hazardous material was minimized. See, J. Am. Chem. Soc, 1992, 114(23), 9237-8; US Patent No. 5,117,063; US Patent No.5, 253, 737; US Patent No. 5,331,099; US Patent No.5, 453, 541; US Patent No. 5,552,531; and US Patent No 5,633,407. These processes, however, are disadvantageous in that relatively expensive TMA(OH) is used, and it is difficult for the used TMA(OH) to be recovered. In addition, these processes have another problem in that 2- nitrodiphenylamine (hereinafter, called "2-NDPA") and phenazine are produced as byproducts with the reaction of aniline at the ortho position of nitrobenzene, thereby reducing the purity of the product. Additionally, other known processes using a NASH reaction include a process of preparing 4-ADPA by the reaction of aniline with azobenzene in the presence of a base such as TMA(OH). See, J. Org. Chem. , 1994, 59(19), 5627-5632; US Patent No. 5,382,691; US Patent No. 5,618,979; EP Patent No 726,889; WO 95/12569; and JP Patent No. 9,504,546.

Disclosure of the Invention

The present invention employs the NASH reaction. Moreover, the invention employs anilide instead of aniline as a starting material. The invention thus is a process for preparing 4-NDPA by reacting nitrobenzene with anilide. The invention is advantageous in that it employs relatively cheap alkaline base without generating the byproducts with the ortho position reaction problematic when using aniline.

The present invention relates to a process for the preparation of 4-NDPA, in which carbanilide among anilide used as a starting material is reacted with nitrobenzene in the presence of a base to obtain 4-NDPA. This 4-NDPA is mainly used as the raw material for preparing 4-ADPA, which is an intermediate to the antioxidant, by hydrogenation. This invention is advantageous in that it employs, as a starting material, carbanilide which is easily obtained from urea and aniline, and also employs a base such as sodium hydroxide, while selectively producing 4-NDPA of high yield.

The prior art regarding the reaction of aniline with nitrobenzene was problematic in separating 4-NDPA because the presence of 2-NDPA and phenazine byproducts are produced by the reaction at the ortho position of nitrobenzene. However, where carbanilide is used as a starting material in accordance with the invention, the generation of the byproducts by the reaction at the ortho position of nitrobenzene can be highly reduced due to the steric hindrance of an amide structure.

Moreover, in accordance with the invention, the change of the reaction atmosphere, for example, to oxygen, or the control of the base and the reaction temperature eliminates the production of azobenzene and azoxybenzene problematic in the prior art processes, so as to increase the selectivity to 4-NDPA.

This invention is advantageous in that 4-NDPA can be obtained at high yield by using a base such as, for example, alkali metal or alkaline earth metal. Also, in this invention, since there is no generation of the corrosive waste water, such as, waste water containing chlorine, a factor corrosive to the reactor is eliminated. Additionally, as the reaction yield is not substantially influenced by water, no need remains to use a drying agent separately, or to install a distillation device. This results in a decrease in the production cost.

Best Mode for Carrying Out the Invention

This invention relates to a process of synthesizing

4-NDPA, wherein carbanilide as a starting material is dissolved in a polar organic solvent, a base is added to the resultant solution, and the mixture is reacted with nitrobenzene to obtain 4-NDPA. Solvent used in the process of this invention is chosen taking a solubility of carbanilide, its miscibility with a base, etc. into consideration. Examples of this solvent include, but are not limited to, polar organic solvents, such as dimethylsulfoxide (hereinafter, called "DMSO"), dimethylformamide (hereinafter, called "DMF"), N-methyl-2- pyrrolidinone, nitrobenzene, aniline and the like. Among these solvents, the cases of DMSO, DMF, and N-methyl-2- pyrrolidinone show an excellent reactivity. In particular, the case of DMSO provides the highest yield. The volume ratio of the solvent to the nitrobenzene is in the range of about 100:1 to about 1:1, with the preferred ratio being in the range of about 30:1 to about 1:1. Examples of the base used include, but are not limited to, organic or inorganic bases, such as sodium hydroxide (NaOH) , potassium hydroxide (KOH) , calcium hydroxide (Ca (OH) ₂) , potassium t-butoxide (t-BuOK) , tetramehtylammonium hydroxide, sodium hydride (NaH) , calcium hydride (CaH₂) and the like. Besides the above- mentioned bases, a base such as an alkali metal or an alkaline earth metal may be also used. Among these bases, sodium hydroxide, potassium hydroxide and sodium hydride show a high reactivity and yield. The molar ratio of the base to carbanilide is in the range of about 1:10 to about 10:1, with the preferred ratio being in the range of about 2:1 to about 6:1.

The ratio of moles of the nitrobenzene to the carbanilide is in the range of about 0.5:1 to about 20:1, with the higher the amount of nitrobenzene used, the faster the reaction rate and the higher the reaction yield in the same period of time. However, if the amount of nitrobenzene is in excess of the necessary amount, azoxybenzene as a byproduct is produced to lower the selectivity to 4-NDPA. The reaction temperature is in the range of a temperature between about 20°C and about 150°C, preferably between about 50 °C and about 80°C. If the reaction temperature is lower than about 20°C, the reaction rate becomes slow. If the reaction temperature is higher than about 150°C, the production of the byproduct increases. To remove water produced in the reaction solution upon beginning of or during the reaction, a vacuum distillation is performed, or a drying agent is used. Material useful as the drying agent, for example, includes anhydrous potassium carbonate, anhydrous sodium sulfate, anhydrous magnesium sulfate, sodium hydroxide, potassium hydroxide, sodium hydride, molecular sieves, and the like. However, as the process of this invention is not substantially influenced by the amount of water during the reaction, there is no significant differential in the yield between the use of the drying agent and the carrying out of the distillation. The reaction can be carried out under a nitrogen or oxygen atmosphere or in the air. In a nitrogen atmosphere, there is produced the byproduct, such as azobenzene, azoxybenzene and the like, whereas in an oxygen atmosphere, the production of the byproduct is inhibited so as to increase the selectivity to 4-NDPA.

Examples

The following examples are for illustration purposes only and in no way limit the scope of this invention. In the following examples, the reactants and products were analyzed by the Nuclear Magnetic Resonance (NMR) spectrum and the Gas Chromatography-Mass Spectroscopy Detector to identify them. Also, the reactants and products were analyzed by gas chromatography to determine their quantitative analysis values in accordance with the following conditions: Capillary column: ULTRA 2 (Crosslinked 5% Ph Me

Silicon) 50mm X 0.2mm X 0.33μm. Carrier gas: nitrogen Head pressure: 18 psig Oven: 100°C(2min.) to 280°C, β=10°C/min.

Detector and temperature: FID(280°C) . Split ratio: 50:1 Make up gas flow rate: 38mm.

For the quantitative analysis of each product, pyrene was used as an internal standard. By applying the gas chromatography factor of the internal standard to the area ratio, the molar ratio of a product to carbanilide as a reactant was calculated.

Example 1 Into a 100ml three-neck flask equipped with a condenser and a stirrer were charged 1.77g (8.34mmole) of carbanilide, 10ml (78. Ommole) of nitrobenzene, 0.8g (33.3mmole) of sodium hydride and 20ml of DMSO, and the resultant mixture was then stirred at a temperature of 60°C under an atmosphere of oxygen for 4 hours. Upon the beginning of the reaction, lOOmg of pyrene was added as an internal standard. After extracting the resultant reaction solution with ethyl acetate, an analysis of the resultant product by gas chromatography revealed 4-NDPA was produced in 99mole% yield (8.29mmole, 1.78g).

Example 2

This example illustrates the effect of the varying kinds of bases on the yields of 4-NDPA.

Into a 100ml three-neck flask equipped with a condenser and a stirrer were charged 1.5g (7.07mmol) of carbanilide, 5ml (48.7mmole) of nitrobenzene, 28.3mmole of sodium hydroxide as a base and 30ml of DMSO, and the resultant mixture was then left to react at a temperature of 80°C under an atmosphere of oxygen for 3 hours. Upon the beginning of the reaction, lOOmg of pyrene was added as an internal standard. After extracting the resultant reaction solution with ethyl acetate, an analysis of the resultant product by gas chromatography was performed to determine 4-NDPA. The above experiment was repeated several times with varying kinds of bases as listed in Table 1 below. The analysis results are shown in Table 1.

Table 1 Kind of Base Yield of 4-NDPA (mole% )

Sodium hydroxide 91 Sodium hydride 88

Potassium hydroxide 79

Potassium t-butoxide 40

Calcium hydroxide < 1

Calcium hydride 0

Example 3

This example illustrates the effect of the varying amounts of a base on the yield of the product.

In a 100ml three-neck flask equipped with a condenser and a stirrer, 1.5g (7. Ommole) of carbanilide and 5ml (48.7mmole) of nitrobenzene were dissolved in 30ml of

DMSO. Following this, sodium hydroxide, as a base, of the amount shown in Table 1 below was added to the solution, and the resultant mixture was then stirred at a temperature of 80°C under an atmosphere of oxygen for 3 hours. Upon the beginning of the reaction, lOOmg of pyrene was added as an internal standard. After extracting the resultant reaction solution with ethyl acetate, an analysis of the obtained product by gas chromatography was performed to determine 4-NDPA. The above experiment was repeated three times, each time with varying amounts of a base as listed in Table 2 below. The analysis results are shown in Table 2.

Table 2 Amount of base* Yield of 4-NDPA (mol%)

1 37

2 77

4 96

*The amount of the base was expressed in terms of the equivalent ratio of sodium hydroxide to carbanilide.

Example 4

This example illustrates the effect of the drying agent on the yield of the product.

In a 100ml three-neck flask containing 2.0g of potassium carbonate as a drying agent and equipped with a condenser and a stirrer, 1.5g (7.07mmol) of carbanilide, 5ml (48.7mmol) of nitrobenzene and l.lg of sodium hydroxide were dissolved in 30ml of DMSO. Following this, the resultant mixture was then left to react at a temperature of 80°C under an atmosphere of oxygen for 3 hours. Upon the beginning of the reaction, lOOmg of pyrene was added as an internal standard. After extracting the resultant reaction solution with ethyl acetate, an analysis of the obtained product was performed by gas chromatography to determine 4-NDPA. Also, the above described experiment was repeated twice, each time with 2.0g of Molecular sieve 4A as the drying agent or without the drying agent. The analysis results are shown in Table 3 below.

Table 3 Drying agent 4-NDPA (mole% )

None 91

Potassium carbonate 96

Molecular sieve 4A 93

Example 5 This example illustrates the effect of the varying reaction temperatures on the yield of 4-NDPA.

In a 100ml three-neck flask containing 2.0g of calcium carbonate as a drying agent and equipped with a condenser and a stirrer, 1.5g (7.07mmol) of carbanilide, 5ml (48.7mmol) of nitrobenzene and l.lg of sodium hydroxide were dissolved in 30ml of DMSO. Following this, the resultant mixture was stirred to react at a temperature of 80°C under an atmosphere of oxygen for 3 hours. Upon the beginning of the reaction, lOOmg of pyrene was added as the internal standard. After extracting the resultant reaction solution with ethyl acetate, an analysis of the reaction product was performed by gas chromatography to determine 4-NDPA. The above experiment was repeated with varying reaction temperatures as listed in Table 4 below. The analysis results are shown in Table 4.

Table 4

Reaction temperature 4-NDPA (mole%)

80°C 96

50°C 62

Room temperature 5

Example 6

This example illustrates the effect of the varying kinds of the reaction solvents on the yield of 4-NDPA.

In a 100ml three-neck flask equipped with a condenser and a stirrer, 1.5g (7.07mmol) of carbanilide, 5ml (48.7mmol) of nitrobenzene and l.lg of sodium hydroxide were dissolved in 30ml of DMSO. Following this, the resultant mixture was left to react at a temperature of 80°C under an atmosphere of oxygen for 3 hours. Upon the beginning of the reaction, lOOmg of pyrene was added as the internal reference. After extracting the resultant reaction solution with ethyl acetate, the product was analyzed by gas chromatography to determine 4-NDPA. The above experiment was repeated several times with varying kinds of solvents as listed in Table 5 below. The analysis results are shown in Table 5.

Table 5 Kind of reaction solvent 4-NDPA (mole% )

DMSO 91 N-methyl-2-pyrrolidinone 42

DMF 30

Nitrobenzene < 1

Example 7 This example shows the effect of the varying reaction atmosphere on the amounts and kinds of byproduct produced.

Into a 100ml three-neck flask equipped with a condenser and a stirrer were charged 1.77g ( 8.34mmol) of carbanilide, 4ml (39. Ommol) of nitrobenzene, 0.8g of sodium hydroxide and 20ml of DMSO, and the resultant mixture was then left to react at a temperature of 60 °C under an atmosphere of oxygen for 2 hours. Upon the beginning of the reaction, lOOmg of pyrene was added as the internal standard. After extracting the resultant reaction solution with ethyl acetate, the product was analyzed by gas chromatography to determine 4-NDPA and the byproduct. The above experiment was repeat using a nitrogen atmosphere instead of the oxygen atmosphere. The analysis results are shown in Table 6 below.

Table 6

Atmosphere 4-NDPA Azoxybenzene Azobenzene (mole%) (mole%) (mole%)

Oxygen 90 < 1 not detected

Nitrogen 71 28 1

Example 8 This example illustrates the effect of the varying amounts of nitrobenzene on the yield of 4-NDPA.

In a 100ml three-neck flask equipped with a condenser and a stirrer, 1.77g (8.34mmol) of carbanilide, nitrobenzene, and 0.8g (33.3mmol) of sodium hydride were dissolved in 20 ml of DMSO, and the resultant mixture was then left to react at a temperature of 60 °C under an atmosphere of oxygen for 2 hours. Upon the beginning of the reaction, lOOmg of pyrene was added as the internal standard. After extracting the resultant reaction solution with ethyl acetate, an analysis of the product by gas chromatography was performed to determine 4-NDPA. The above experiment was repeated several times with varying amounts of nitrobenzene as listed in Table 7 below. The analysis results are shown in Table 7.

Table 7

Nitrobenzene/carbanilide 4-NDPA (mole% ) (mole/mole)

1.2 47

2.3 79

4.7 90

9.4 99

Comparative example

This comparative example illustrates a decrease in the yield of 4-NDPA when employing the aniline used instead of carbanilide as a starting material.

In a 100ml three-neck flask containing 2g of potassium carbonate as a drying agent and equipped with a condenser and a stirrer, 1.3g (14. Ommol) of aniline, 5ml (48.7mmol) of nitrobenzene, and 1. lg (27.5mmol) of sodium hydroxide were dissolved in 30 ml of DMSO, and the resultant mixture was then left to react at a temperature of 60 °C under an atmosphere of oxygen for 3 hours. Upon the beginning of the reaction, lOOmg of pyrene was added as the internal standard. After extracting the resultant reaction solution with ethyl acetate, an analysis of the product by gas chromatography revealed 4-NDPA and azobenzene were produced in 2.7% (0.038mmole, 81mg) yield and 8.6% (1.20mmole, 219mg) yield, respectively.

Industrial Applicability

The process according to this invention is advantageous in that relatively cheap alkaline salts is used, and 4-nitrodiphenylamine can be produced at high selectivity and conversion without generating the environmentally hazardous corrosive reaction byproduct.

Although the preferred embodiments of the invention have been disclosed for illustrative purposes, those skilled in the art will appreciate that various modifications, additions and substitutions are possible, without departing from the scope and spirit of the invention as disclosed in the accompanying claims.

Claims

1. A process for preparing 4-nitrodiphenylamine by a nucleophilic aromatic substitution for hydrogen, comprising reacting carbanilide and nitrobenzene in a polar organic solvent in the presence of a base.

2. The process of claim 1, wherein the base is selected from the group consisting of sodium hydroxide, potassium hydroxide, calcium hydroxide, potassium t- butoxide, tetramethylammonium hydroxide, sodium hydride, and calcium hydride.

3. The process of claim 1, wherein the polar organic solvent is selected from the group consisting of dimethylsulfoxide, dimethylformamide, N-methyl-2- pyrrolidinone, nitrobenzene, aniline.

4. The process of claim 1, wherein the reaction temperature is in the range of a temperature of from about 20°C to about 150°C.

5. The process of claim 1, wherein the reaction atmosphere is in oxygen, nitrogen, or air.

6. A process for preparing 4-nitrodiphenylamine by a nucleophilic aromatic substitution for hydrogen, comprising reacting carbanilide and nitrobenzene in a polar organic solvent in the presence of a base and a drying agent.

7. The process of claim 6, wherein the base is selected from the group consisting of sodium hydroxide, potassium hydroxide, calcium hydroxide, potassium t- butoxide, tetramethylammonium hydroxide, sodium hydride, and calcium hydride.

8. The process of claim 6, wherein the drying agent is selected from the group consisting of anhydrous potassium carbonate, anhydrous sodium sulfate, anhydrous magnesium sulfate, sodium hydroxide, potassium hydroxide, sodium hydride, and molecular sieves.

9. The process of claim 6, wherein the polar organic solvent is selected from the group consisting of dimethylsulfoxide, dimethylformamide, N-methyl-2- pyrrolidinone, nitrobenzene, aniline.

10. The process of claim 6, wherein the reaction temperature is in the range of a temperature of from about

20°C to about 150°C.

11. The process of claim 6, wherein the reaction atmosphere is in oxygen, nitrogen, or air.