Title of Invention

"METHOD FOR PREPARING P-AMINOBENZOIC ACID"

Abstract

The invention provides for a method for preparing p-aminobenzoic acid comprising the steps of: a. chlorinating methyl-4-formylbenzoate at a temperature of 40 to 200°C to produce methyl-4-chloroformylbenzoate; b. amidating the methyl-4-chloroformylbenzoate at a temperature of 1 to 50°C to produce methyl-4-chloroformylbenzoate; and c. carrying out Hofmann reaction with the produced methyl-4- carbamoylbenzoate in aqueous solution at a temperature of 0 to 80°C.

Full Text

METHOD FOR PREPARING P-AMINOBENZOIC ACID FIELD OF THE INVENTION The present invention relates to a method for preparing p-aminobenzoic acid (hereinafter, "PABA"), and more particularly, to a method for preparing p-aminobenzoic acid using methyl-4-formyibenzoate as a starting material which is a major by-product produced while synthesizing dimethylterephthalate (hereinafter, "DMT"). BACKGROUNDS OF THE INVENTION P-aminobenzoic acid (PABA) is a yellow crystalline compound which can be dissolved in water, ethanol and ether. PABA is widely used in various chemical industries, and its exemplary application area includes UV absorber of a sunscreen cream, raw material of an aromatic, polymer ingredient, intermediate for producing a direct dye or a vat dye, pharmaceutical intermediate, and raw material of a cofactor of vitamin B for animal feeds, a vitamin Bx, and a local anesthetic such as benzocaine and procaine. The conventional process for producing PABA is shown in the following reaction 1 [Reaction 1] (Formula Removed) As show in the reaction 1, toluene is nitrated to produce o-nitrotoluene and p-nitrotoluene, and the produced o-nitrotoluene and p-nitrotoluene are separated from each other. Then p-nitrotoluene is oxidized to produce p-nitrobenzoic acid. In the last step, the nitro group of p-nitrobenzoic acid is reduced with hydrogenation catalyst such as hydrochloric acid - tin mixture, platinum, and Raney nickel, which produces the target compound, PABA. However, the method of reaction 1 has disadvantages in that ortho- and para- isomers are simultaneously formed by nitration of toluene, and the isomers should be separated with a separation method such as a fractional crystallization. In particular, the ortho-isomer is not a useful compound, and generally is discarded as by-product, which increases the production cost of PABA. In addition, the oxidizing agent such as hydrogen peroxide and manganese dioxide used for oxidizing p-nitrotoluene, and the reducing agent such as Pt-catalyst and Fe-catalyst used for reducing p-nitrobenzoic acid are expensive chemical compounds, which also increases the production cost of PABA. As an alternative method, United States Patent No. 3,931,210 discloses a method of using monomethylester of terephthalic acid as a starting material to produce PAE3A The monomethylester of terephthalic acid can be obtained in a large quantity as a by-product when synthesizing dimethylterephthalate (DMT) which is a major raw material of polyester resin. In the method, monomethylester of terephthalic icid reacts with ammonia to produce mono-amide compound, and the mono-anmi'; compound is converted into PABA by Hofmann reaction. As the monomethylester of terephthalic acid, lithium, calcium or magnesium salt of the monomethylester of terephthalic acid can be used. However, the monomethylester of terephthalic acid can be obtained in a large quantity from the industrial and commercial process of producing dimethylterephthalate. Thus, monomethylester of terephthalic acid is the most preferable starting material in view of the production cost. However, the method has drawbacks in that the amount of monomethylester of terephthalic acid obtained while synthesizing dimethylterephthalate is not enough to sufficiently reduce the production cost of PABA, and the amidation reaction of monomethylester of terephthalic acid requires high pressure and high temperature. SUMMARY OF THE INVENTION It is an object of the present invention to provide a novel and economical method for preparing p-aminobenzoic acid with a by-product of DMT synthesizing process. It is other object of the present invention to provide the method for preparing p-aminobenzoic acid without purifying the by-product of DMT synthesizing process. It is another object of the present invention to provide the method for preparing p-aminobenzoic acid without using a protecting group and without using a separation process. In order to achieve these objects, the present invention provides a method for preparing p-aminobenzoic acid, which comonses the steps of: chlorinating methyl-4-formylbenzoate to produce methyl-4-chlo"oformylbenzoate; amidating the methyl-4-chloroformylbenzoate to produce methyl-4-carbamoylbenzoate; and carrying out Hofmann reaction with the produced methyl-4-carbamoylbenzoate in aqueous solution. In the method, the chlorinating step is preferably carried out by melting methyl-4-formylbenzoate to a liquid phase, and adding 1 to 3 molar equivalent of chlorine gas(CI2). The amidating step is preferably carried out by adding methyl-4-chloroformylbenzoate dissolved in organic solvent into aqueous ammonia, or by supplying ammonia gas into methyl-4-chloroformylbenzoate dissolved in organic solvent. The Hofmann reaction is preferably carried out by adding halogenated base into methyl-4-carbamoylbenzoate dissolved in aqueous alkaline solution. DETAILED DESCRIPTION OF THE INVENTION A more complete appreciation of the invention, and many of advantages thereof, will be readily apparent, as the same becomes better understood by reference to the following detailed description. The starting material, methyl-4-formylbenzoate (MFB) for preparing p-aminobenzoic acid according to the present invention is a major by-product of DMT synthesizing process. DMT is a raw material which is used for producing polyester resin, and conventionally synthesized according to the following Reaction 2, wherein Me represents methyl group. [Reaction 2] (Formula Removed) 5 The composition of the by-products produced in the above-identified DMT synthesizing process changes according to the conditions of the synthesizing process. When the reaction rate of the synthesizing process increases, the produced by-products include 80wt% of methyl-4-formylbenzoate (MFB), 9wt% of DMT, 4wt% of methyl-p-toluate(MPT), thus methyl-4-formylbenzoate is the major by-product. World-widely, it is known that Eastman Kodak Co., E.I. du Pont de Nemours and company, and SK chemicals Co., Ltd adapt such DMT synthesizing process, and the produced by-products are generally discarded or incinerated. The present invention uses methyl-4-formylbenzoate as a starting material to prepare p-aminobenzoic acid as shown in the following Reaction 3. [Reaction 3] (Formula Removed) As shown in Reaction 3, in the first step, methyl-4-formylbenzoate is chlorinated to produce methyl-4-chloroformylbenzoate. The chlorination step is preferably carried out by melting the methyl-4-formylbenzoate to a liquid phase in an atmospheric pressure, and adding 1 to 3 molar equivalent of chlorine gas(CI2). The melting temperature of the reactant, methyl-4-formylbenzoate, is preferably 40 to 200°C, more preferably 40 to 100°C, and most preferably 50-70°C. When the melting temperature is less than 40°C, the reactant, methyl-4-formylbenzoate, cannot be sufficiently melted, and reaction rate becomes slow, which prevents the efficient reaction. When the melting temperature is more than 200°C, energy consumption increases, side-reactions may occur, and the reaction yield decreases remarkably. If less than 1 molar equivalent of chlorine gas(CI2) is used, the reaction cannot be completely carried out, and even if more than 3 molar equivalent of chlorine gas(CI2) is used, the reaction yield cannot further increases. The product of the chlorination process is in the liquid phase in the reaction temperature, and the reaction time is generally about 10 hours, and the reaction yield is about 90%. As the second step, methyl-4-chloroformylbenzoate produced by the chlorination process is amidated to produce methyl-4-carbamoylbenzoate. The amidation reaction is preferably carried out by reacting methyl-4-chloroformylbenzoate with aqueous ammonia(NH4OH) or ammonia gas(NH3) in water and/or organic solvent. In detail, the amidation reaction is preferably carried out by dropwisely adding methyl-4-chloroformylbenzoate in a melted phase into aqueous ammonia, by dropwisely adding methyl-4-chloroformylbenzoate dissolved in organic solvent into aqueous ammonia, or by supplying ammonia gas into methyl-4-chloroformylbenzoate dissolved in organic solvent. The organic solvent for the amidation process includes various organic solvent which can dissolve methyl-4-chloroformylbenzoate, and the preferable example of the organic solvent includes hydrophobic organic solvents such as toluene, ethylacetate, and mixture thereof The amount of the organic solvent is preferably 0 to 10 times with respect to methyl-4-chloroformylbenzoate in weight, more preferably 0.5 to 8 times with respect to methyl-4-chloroformylbenzoate in weight. In the amidation step, methyl-4-carbamoylbenzoate is produced in a solid phase, thus can be easily separated from aqueous solution and from various by- products. The impure by-products, such as methyl-p-toluate and dimethlyterephthalic acid in the reactor dissolve in organic solvent and separated from solid methyl-4-carbamoylbenzoate. The amidation step can be carried out at atmospheric pressure, and the reaction temperature is preferably 1 to 50°C, more preferably 3 to 30°C. If the nitrogen source is ammonia gas, the amidation reaction is preferably carried out at relatively high temperature, for example at 25°C to increase the gas activity. If the reaction temperature is less than 1°C, the reaction rate decreases, and if the reaction temperature is more than 50°C, side reactions may occur. The amount of the organic solvent depends on the amount of impurities. If the organic solvent of more than 10 times with respect to methyl- 4-chloroformylbenzoate is used, the reaction efficiency decreases, and the production cost increases. In the amidation step, when the nitrogen source is aqueous ammonia (NH4OH), the amount of the aqueous ammonia is 5 to 20 molar equivalent, preferably 7 to 15 molar equivalent. When the nitrogen source is ammonia gas (NH3), the amount of the ammonia gas is 1.5 to 5 molar equivalent, preferably 2 to 3 molar equivalent. If the amounts of the aqueous ammonia (NH4OH) and ammonia gas (NH3) are less than 5 and 1.5 molar equivalent, respectively, the reaction rate decreases. If the amounts of the aqueous ammonia (NH4OH) and ammonia gas (NH3) are more than 20 and 5 molar equivalent, respectively, additional favorable effect would not occur. The product of ine amidation step is white crystalline compound, the reaction time is about 1 hour, and the reaction yield is about 98% As the final step, Hofmann reaction is carried out with methyl-4-carbamoylbenzoate to produce p-aminobenzoic acid. For example, the Hofmann reaction is carried out by reacting methyl-4-carbamoylbenzoate with 1 to 1.5 molar equivalent of halogenated base, such as NaOCl and NaOBr, and 3 to 15 molar equivalent of NaOH in aqueous solution, or the Hofmann reaction is carried out by adding the halogenated base into methyl-4-carbamoylbenzoate dissolved in aqueous alkaline solution. The temperature of the Hofmann reaction is 0 to 80°C, preferably 3 to 60°C, the reaction pressure is atmospheric pressure, and the reaction time is about 2 hours. If the amounts of the reactants are less than above-identified limits, the reaction yield decreases, and even if the amounts of the reactants are more than above-identified limits, additional increase of the reaction yield may not occur. If the temperature of the Hofmann reaction is less than 0°C, the reaction rate decrease, and if the temperature of the Hofmann reaction is more than 80°C, side-reactions may occur. When the Hofmann reaction is complete, p-aminobenzoic acid can be extracted with aqueous acid, preferably with 5 to 10% HCI aqueous solution, then pH of the reactant is neutralized to about 4 with a base, preferably with NaOH to precipitate solid p-aminobenzoic acid. Then the reactant is filtered to obtain pure p-aminobenzoic acid The yield of the Hofmann reaction is about 90%. Hereinafter, the preferable examples are provided for better understanding of the present invention. However, the present invention should not be restricted to the following Examples. [Example 1] 75% methyl-4-formylbenzoate (methyl-4-formylbenzoate 16.4g) was melted at 60°C. and 1.5 molar equivalent of chlorine gas (Cl2) was added thereto while bubbling for 10 hours to obtain methyl-4-chloroformylbenzoate with the yield of 90%. 19.8g of methyl-4-chloroformylbenzoate dissolved in 80g of toluene at 60°C was dropwisely added into 10% aqueous ammonia for 2 hours, which includes 10 molar equivalent of ammonia with respect to methyl-4-chloroformylbenzoate. In this reaction, the reaction temperature was maintained at 5 to 20°C. Then, cooling of the reactant was stopped to increase the temperature of the reactant to room temperature. The reactant was filtered to obtain white crystalline methyl-4-carbamoylbenzoate with the yield of 98% and the purity of 95%. 1N aqueous sodium hydroxide solution including 5 molar equivalent of sodium hydroxide with respect to methyl-4-carbamoylbenzoate is cooled to 0°C, and 17.9g of methyl-4-carbamoylbenzoate was added thereto. While maintaining the temperature of the reactant at 0 to 10°C, 10% aqueous NaOC! solution including 1.05 molar equivalent of NaOCI was added into the reactant for 30 minutes, and the reaction was continued for 2 hours. Then, the temperature of the reactant was increased to 50°C, and maintained for 1 hour. By adding aqueous NaOH, the pH of the reactant was adjusted to 4, and sono target compound was precipitated. By filtering the reactant, the target compound, p- aminobenzoic acid was obtained with the yield of 95%. [Example 2] Instead of 60°C methyl-4-chloroformylbenzoate, methyl-4-chloroformylbenzoate dissolved in ethylacetate was used. The volume of ethylacetate was 4 times of methyl-4-chloroformylbenzoate. Except that, p-aminobenzoic acid was obtained according to the same method shown in Example 1. The yield of the amidation reaction was 95%, and purity of the obtained amide compound was 96%. [Example 3] 2 molar equivalent of anhydrous ammonia gas was added into methyl-4-chloroformylbenzoate dissolved in toluene for 2 hours while bubbling. The volume of toluene was 4 times of methyl-4-chloroformylbenzoate. Then, toluene was distilled off, and the reactant was washed with pure water, and filtered to obtain white crystalline methyl-4-carbamoylbenzoate with the yield of 96%. Except that, p-aminobenzoic acid was obtained according to the same method shown in Example 1. As described, the method for preparing p-aminobenzoic acid according to the present invention is a novel process. In the process, methyl-4-formylbenzoate, which can be obtained as by-product in DMT synthesizing process, is used as a starting material without purification to produce p-aminobenzoic acid. The impurities in the methyl-4-formylbenzoate are removed during the steps for preparing p-aminobenzoic acid. The novel process of the present invention utilizes the asymmetry of methyl-4-formylbenzoate compound, and a protecting group is not required for the process. Therefore, the steps for preparing p-aminobenzoic acid of the present invention are simple, and the production cost can be reduced. In the present invention, other purification process can be applied between the steps of the method for preparing p- aminobenzoic acid, or can be applied after producing the target compound, p- aminobenzoic acid. While the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art will appreciate that various modifications and substitutions can be made thereto without departing from the spirit and scope of the present invention as set forth in the appended claims. We claim:- 1. A method for preparing p-aminobenzoic acid comprising the steps of: a. chlorinating methyl-4-formylbenzoate at a temperature of 40 to 200°C to produce methyl-4-chloroformylbenzoate; b. amidating the methyl-4-chloroformylbenzoate at a temperature of 1 to 50°C to produce methyl-4-chloroformylbenzoate; and c. carrying out Hofmann reaction with the produced methyl-4- carbamoylbenzoate in aqueous solution at a temperature of 0 to 80°C. 2. The method as claimed in claim 1, wherein the chlorinating step is carried out by melting methyl-4-chloroformylbenzoate to a liquid phase, and adding 1 to 3 molar equivalent of chlorine gas (CI2). 3. The method as claimed in claim 1, wherein the amidating step is carried out by adding methyl-4-chloroformylbenzoate dissolved in organic solvent into aqueous ammonia solution. 4. The method as claimed in claim 1, wherein the amidating step is carried out by supplying ammonia gas into methyl-4-chloroformylbenzoate dissolved in organic solvent. 5. The method as claimed in claim 1, wherein the Hofmann reaction is carried out by adding halogenated base into methyl-4-carbamoylbenzoate dissolved in aqueous alkaline solution. 6. The method as claimed in claim 3 or 4, wherein the organic solvent is selected from the group consisting of toluene, ethylacetate and mixture thereof. 7. A method for preparing p-aminobenzoic acid substantially as herein described with reference to the foregoing examples.

Documents:

2189-delnp-2004-abstract.pdf

2189-delnp-2004-assignment.pdf

2189-delnp-2004-claims.pdf

2189-delnp-2004-complete specification (as files).pdf

2189-delnp-2004-complete specification (granted).pdf

2189-delnp-2004-correspondence-others.pdf

2189-delnp-2004-correspondence-po.pdf

2189-delnp-2004-description (complete).pdf

2189-delnp-2004-form-1.pdf

2189-delnp-2004-form-19.pdf

2189-delnp-2004-form-2.pdf

2189-delnp-2004-form-3.pdf

2189-delnp-2004-form-5.pdf

2189-delnp-2004-gpa.pdf

2189-delnp-2004-pct-304.pdf

2189-delnp-2004-pct-409.pdf

2189-delnp-2004-petition-138.pdf