CN105218375A - A kind of synthetic method of 2-methyl-4-nitrobenzoic acid - Google Patents

Abstract

The invention discloses a synthesis method of 2-methyl-4-nitrobenzoic acid, belonging to the technical field of chemical synthesis. The present invention uses toluene as a raw material, adding concentrated nitric acid and concentrated sulfuric acid into the mixed reaction solution, washing with sodium hydroxide solution, reacting with tin dichloride, iron powder and glacial acetic acid, and then adding hydrochloric acid dropwise to obtain 2 -Amino-5-nitrotoluene, mixed with acetic acid and concentrated sulfuric acid, after the oxidation of the oxidant sodium perborate, cooling in ice water, washing with deionized water, and then under the oxidation of the oxidant potassium permanganate, Mixed reaction with hydrochloric acid, then stand, filter and dry in the system. The beneficial effects of the invention are: the synthesis process of the method is simple, the cost is low, and the by-products are few; the yield of the obtained product is as high as 95%, and the purity is as high as 99%.

Description

A kind of synthetic method of 2-methyl-4-nitrobenzoic acid

technical field

The invention relates to a synthesis method of 2-methyl-4-nitrobenzoic acid, which belongs to the technical field of chemical synthesis.

Background technique

Benzoic acid, also known as benzoic acid, is the simplest aromatic acid in which the carboxyl group is directly connected to the carbon atom of the benzene ring. It is a compound formed by replacing a hydrogen on the benzene ring with a carboxyl group (-COOH). It is a colorless, odorless flaky crystal. Its vapor is highly irritating and can easily cause coughing after inhalation. Slightly soluble in water, easily soluble in organic solvents such as ethanol, ether, chloroform, benzene, toluene, carbon disulfide, carbon tetrachloride and turpentine. It exists widely in nature in the form of free acid, ester or its derivatives. For example, it exists in the form of free acid and benzyl ester in benzoin gum; it exists in free form in the leaves and bark of some plants; in incense Essential oil exists in the form of methyl ester or benzyl ester; in horse urine, it exists in the form of its derivative hippuric acid. Benzoic acid is a weak acid, stronger than fatty acids. Their chemical properties are similar, and they can form salts, esters, acid halides, amides, acid anhydrides, etc., and are not easily oxidized. The electrophilic substitution reaction can occur on the benzene ring of benzoic acid, and the meta-substituted product is mainly obtained. Benzoic acid is generally used as a medicine or preservative, and has the effect of inhibiting the growth of fungi, bacteria, and mold. It is usually applied on the skin when it is used as medicine to treat skin diseases such as ringworm. Used in synthetic fiber, resin, paint, rubber, tobacco industry. Initially, benzoic acid was obtained by dry distillation of benzoin gum or hydrolysis of alkaline water, and also by hydrolysis of hippuric acid. Industrially, benzoic acid is obtained by air oxidation of toluene in the presence of cobalt, manganese and other catalysts; or by hydrolysis and decarboxylation of phthalic anhydride. Benzoic acid and its sodium salt can be used as a bacteriostatic agent for latex, toothpaste, jam or other foods, as well as a mordant for dyeing and printing.

2-Methyl-4-nitrobenzoic acid synthesized from benzoic acid is an important pharmaceutical intermediate, which can be used to synthesize a series of new antitumor drugs. At present, the synthetic methods of 2-methyl-4-nitrobenzoic acid mainly contain the following kinds, 2-methyl-4-nitrobenzonitrile hydrolysis method, 4-nitro-o-xylene oxidation method and 2-methyl Base-4-aminobenzoic acid oxidation method, 2-methyl-4-nitrobenzonitrile hydrolysis method mainly uses hydrochloric acid, hydrogen peroxide-sodium hydroxide system, sulfuric acid, hydrochloric acid two-step method to hydrolyze 2-methyl-4 -nitrobenzonitrile to obtain product 2-methyl-4-nitrobenzoic acid. And 2-methyl-4-nitrobenzonitrile needs to use 2-methyl-4-nitroaniline as raw material, and it is obtained through diazotization and cyanation, while 2-methyl-4-nitro Raw materials for aniline are not readily available. Therefore, the preparation process using raw material 2-methyl-4-nitrobenzonitrile is more complicated, resulting in longer route and complicated process. The 4-nitro-o-xylene oxidation method uses sodium hypochlorite solution to oxidize 4-nitro-o-xylene. While obtaining 2-methyl-4-nitrobenzoic acid (35.8%), the reaction process also generates Equal amounts of 2-methyl-5-nitrobenzoic acid and a small amount of 4-nitrophthalic acid (9.6%). The preparation process of the method is complicated, and the obtained product has low purity, low yield and many by-products. The 2-methyl-4-aminobenzoic acid oxidation method is an N-oxygenase obtained from Streptomyces, which can selectively oxidize the para-amino group of the acidic group on the benzene ring to obtain 2-methyl-4- Nitrobenzoic acid. However, the 2-methyl-4-aminobenzoic acid material is expensive and difficult to obtain, which greatly limits the method of this method. Therefore, on this basis, a synthetic method of 2-methyl-4-nitrobenzoic acid with simple process, few by-products and high yield has been developed, which has important economic and social benefits.

Contents of the invention

The technical problem to be solved by the present invention: Synthesize 2-methanol for 2-methyl-4-nitrobenzonitrile hydrolysis method, 4-nitro-o-xylene oxidation method and 2-methyl-4-aminobenzoic acid oxidation method Base-4-nitrobenzoic acid raw materials are expensive and difficult to obtain, the preparation process is more complicated, and there are many by-products, resulting in long route, complicated process, high production cost and low yield. A kind of 2-methyl-4 -The synthetic method of nitrobenzoic acid, the present invention takes toluene as raw material, after one-step nitration, reacts with tin dichloride, iron powder, hydrochloric acid, then mixes reaction with acetic acid and concentrated sulfuric acid, in oxidant sodium perborate, permanganate Potassium, hydrochloric acid two-step oxidation, standing suction filtration and drying in the system. The method has the advantages of simple synthesis process, low cost, few by-products and high purity of the obtained product.

For achieving the above object, the synthetic route of 2-methyl-4-nitrobenzoic acid of the present invention is:

The synthetic process of 2-methyl-4-nitrobenzoic acid involved in the present invention comprises the following steps:

(1) Take 5-10mL of nitric acid with a mass fraction of 69% and 3-5mL of sulfuric acid with a mass fraction of 98%, put them into a reaction vessel, control the temperature at 60-65°C, and the speed at 100-200r/min, stir and mix, After the mixed acid is cooled to 20°C, slowly add 30-40mL of toluene dropwise at the rate of each drop/5s, stir for 20-30min, put it in a hot water bath for 40-45min, then filter while it is hot, and pour the filtrate into cold water Cool to room temperature, wash with 20-40mL sodium bicarbonate solution until alkaline, and then rinse with water to obtain 2,5-dinitrotoluene;

(2) Add 20-40g tin dichloride and 3-5g iron powder to the above-mentioned 2,5-dinitrotoluene, and add 20-30mL glacial acetic acid at the same time, set the speed at 500-700r/min, stir for 20 ~30min, after the stirring is completed, control the temperature at 80~85°C, add 10~20mL of hydrochloric acid with a mass fraction of 35% dropwise, increase the speed to 900~1200r/min, and stir for 30~50min to obtain 2-amino- 5-nitrotoluene;

(3) Take 20-30mL of the 2-amino-5-nitrotoluene obtained above into a 70mL three-necked flask, add 15-20mL of acetic acid into it, control the temperature at 50-60°C, stir for 30-50min, and pour to Add 10-15 mL of sulfuric acid with a mass fraction of 98% dropwise, keep the temperature constant, and stir magnetically for 1-2 hours to obtain 2-methyl-4-nitroacetanilide;

(4) Add 10-15mL of hydrogen peroxide and 5-7g of sodium perborate to the 2-methyl-4-nitroacetanilide obtained above, and react at a temperature of 200-300°C and a pressure of 1-3MPa for 1- 2h, then add 15-20mL acetic acid to it, lower the temperature to 60-70°C, stir for 30-50min, after the stirring is completed, place in ice water for 3-5min, wash with deionized water to get 2-methyl-4 - nitrophenylacetamide;

(5) Put the 2-methyl-4-nitrophenylacetamide obtained above into an 80-100mL reaction bottle, add 3-5g of potassium permanganate and 15-20mL of sodium hypochlorite to it respectively, at a temperature of 70- 80°C, at a speed of 800-900r/min, stir for 30-40min, slowly add 10-20mL of hydrochloric acid with a mass fraction of 30% dropwise during the stirring process, after the dropwise addition is completed, react for 1-2h, and stand for suction filtration , and dried to give 2-methyl-4-nitrobenzoic acid.

Compared with other methods, the present invention has beneficial technical effects as follows:

(1) The yield of the product obtained in the present invention is as high as 95% or more, and the purity is as high as 99% or more;

(2) The synthesis process of this method is simple, the cost is low, and there are few by-products.

detailed description

First, take 5-10 mL of nitric acid with a mass fraction of 69% and 3-5 mL of sulfuric acid with a mass fraction of 98%, put them into a reaction vessel, control the temperature at 60-65°C, and rotate at a speed of 100-200r/min, stir and mix until the acid is mixed. Cool to 20°C, slowly add 30-40mL of toluene dropwise at the rate of each drop/5s, stir for 20-30min, put it in a hot water bath for 40-45min, then filter while it is hot, pour the filtrate into cold water and cool to At room temperature, wash with 20-40mL sodium bicarbonate solution until alkaline, then rinse with water to obtain 2,5-dinitrotoluene; then add 20-40g tin dichloride to the above-mentioned 2,5-dinitrotoluene and 3~5g of iron powder, and at the same time add 20~30mL of glacial acetic acid, set the speed at 500~700r/min, stir for 20~30min, after the stirring is completed, control the temperature at 80~85℃, add dropwise 10~ 20mL of hydrochloric acid with a mass fraction of 35%, increase the rotational speed to 900-1200r/min, stir for 30-50min to obtain 2-amino-5-nitrotoluene; then take 20-30mL of the 2-amino-5-nitrotoluene obtained above Put toluene in a 70mL three-neck flask, add 15-20mL acetic acid to it, control the temperature at 50-60°C, stir for 30-50min, add 10-15mL sulfuric acid with a mass fraction of 98% dropwise while stirring, and keep the temperature constant. Stir magnetically for 1-2 hours to obtain 2-methyl-4-nitroacetanilide; add 10-15mL hydrogen peroxide and 5-7g sodium perborate to the 2-methyl-4-nitroacetanilide obtained above. 200-300°C and a pressure of 1-3MPa to react for 1-2h, then add 15-20mL acetic acid to it, cool down to 60-70°C, stir for 30-50min, after the stirring is completed, place in ice water for 3- 5min, after washing with deionized water, 2-methyl-4-nitrophenylacetamide was obtained; finally, the 2-methyl-4-nitrophenylacetamide obtained above was put into 80-100mL reaction flask, respectively Add 3-5g of potassium permanganate and 15-20mL of sodium hypochlorite to it, stir for 30-40min at a temperature of 70-80°C and a speed of 800-900r/min, and slowly add 10-20mL of mass fraction dropwise during the stirring process It is 30% hydrochloric acid. After the dropwise addition is completed, react for 1-2 hours, stand for suction filtration, and dry to obtain 2-methyl-4-nitrobenzoic acid.

Example 1

First, take 5mL of nitric acid with a mass fraction of 69% and 3mL of sulfuric acid with a mass fraction of 98%, put them into a reaction vessel, control the temperature at 60°C, and rotate at a speed of 100r/min, stir and mix, wait until the mixed acid is cooled to 20°C, Slowly add 30mL of toluene dropwise at the speed of /5s, stir for 20min, place in a hot water bath for 40min, then filter while hot, pour the filtrate into cold water to cool to room temperature, wash with 20mL of sodium bicarbonate solution until alkaline, and then Rinse with clean water to obtain 2,5-dinitrotoluene; then add 20g of tin dichloride and 3g of iron powder to the above-mentioned 2,5-dinitrotoluene, and add 20mL of glacial acetic acid at the same time, and set the speed at 500r/ min, stirring for 20 min, after the stirring is completed, control the temperature to 80°C, add dropwise 10 mL of hydrochloric acid with a mass fraction of 35%, increase the rotation speed to 900 r/min, and stir for 30 min to obtain 2-amino-5-nitrotoluene; Then take 20mL of the 2-amino-5-nitrotoluene obtained above in a 70mL three-necked flask, add 15mL of acetic acid to it, control the temperature at 50°C, stir for 30min, and add 10mL of sulfuric acid with a mass fraction of 98% dropwise while stirring. , keep the temperature constant, and magnetically stir for 1h to get 2-methyl-4-nitroacetanilide; add 10mL hydrogen peroxide and 5g sodium perborate to the above-mentioned 2-methyl-4-nitroacetanilide respectively. 200°C and a pressure of 1MPa for 1h, then add 15mL of acetic acid, cool down to 60°C, and stir for 30min. -4-nitrophenylacetamide; finally put the 2-methyl-4-nitrophenylacetamide obtained above into the 80mL reaction flask, add 3g potassium permanganate and 15mL sodium hypochlorite therein respectively, at a temperature of 70 ℃, at a rotation speed of 800r/min, stir for 30min, slowly add 10mL of hydrochloric acid with a mass fraction of 30% dropwise during the stirring process, after the dropwise addition is completed, react for 1h, stand and filter, and dry to obtain - Nitrobenzoic acid. The method has the advantages of simple synthesis process, low cost and few by-products; the yield of the obtained product is as high as 95.8%, and the purity is as high as 99.15%.

Example 2

First, take 8mL of nitric acid with a mass fraction of 69% and 4mL of sulfuric acid with a mass fraction of 98%, put them into a reaction vessel, control the temperature at 62°C, and rotate at a speed of 150r/min, stir and mix, wait until the mixed acid is cooled to 20°C, press each drop Slowly add 35mL of toluene dropwise at the speed of /5s, stir for 25min, place in a hot water bath to react for 42min, then filter while hot, pour the filtrate into cold water to cool to room temperature, wash with 30mL sodium bicarbonate solution until alkaline, and then Rinse with water to obtain 2,5-dinitrotoluene; then add 30g of tin dichloride and 4g of iron powder to the above-mentioned 2,5-dinitrotoluene, and add 25mL of glacial acetic acid at the same time, and set the speed at 600r/ min, stirred for 25 min, after the stirring was completed, controlled the temperature to 83°C, added dropwise 15 mL of hydrochloric acid with a mass fraction of 35%, increased the rotation speed to 1100 r/min, and stirred for 40 min to obtain 2-amino-5-nitrotoluene; Then take 25mL of the 2-amino-5-nitrotoluene obtained above in a 70mL three-necked flask, add 18mL of acetic acid to it, control the temperature at 55°C, stir for 40min, and add 13mL of sulfuric acid with a mass fraction of 98% dropwise while stirring. , keep the temperature constant, and stir magnetically for 1.5h to obtain 2-methyl-4-nitroacetanilide; add 12mL hydrogen peroxide and 6g sodium perborate to the 2-methyl-4-nitroacetanilide obtained above, respectively, The temperature was 250°C and the pressure was 2MPa for 1.5h, then 17mL of acetic acid was added thereto, the temperature was lowered to 65°C, and stirred for 40min. After the stirring was completed, it was placed in ice water for 4min and washed with deionized water to obtain 2- Methyl-4-nitrophenylacetamide; finally the 2-methyl-4-nitrophenylacetamide of the above-mentioned gained is put into 90mL reaction bottle, adds 4g potassium permanganate and 17mL sodium hypochlorite respectively thereto, at temperature at 75°C with a rotation speed of 850r/min, stir for 35min, and slowly add 15mL of hydrochloric acid with a mass fraction of 30% dropwise during the stirring process. Base-4-nitrobenzoic acid. The method has the advantages of simple synthesis process, low cost and few by-products; the yield of the obtained product is as high as 96.3%, and the purity is as high as 99.28%.

Example 3

First, take 10mL of nitric acid with a mass fraction of 69% and 5mL of sulfuric acid with a mass fraction of 98%, put them into a reaction vessel, control the temperature at 65°C, and rotate at a speed of 200r/min, stir and mix, wait until the mixed acid is cooled to 20°C, press Slowly add 40mL of toluene dropwise at the speed of /5s, stir for 30min, place in a hot water bath for 45min to react, then filter while hot, pour the filtrate into cold water to cool to room temperature, wash with 40mL sodium bicarbonate solution until alkaline, and then Rinse with water to obtain 2,5-dinitrotoluene; then add 40g of tin dichloride and 5g of iron powder to the above-mentioned 2,5-dinitrotoluene, and add 30mL of glacial acetic acid at the same time, and set the speed at 700r/ min, stir for 30 min, after the stirring is completed, control the temperature to 85°C, add 20 mL of hydrochloric acid with a mass fraction of 35% dropwise therein, increase the rotation speed to 1200 r/min, and stir for 50 min to obtain 2-amino-5-nitrotoluene; Then take 30mL of the 2-amino-5-nitrotoluene obtained above in a 70mL three-necked flask, add 20mL of acetic acid to it, control the temperature at 60°C, stir for 50min, and add 15mL of sulfuric acid with a mass fraction of 98% dropwise while stirring. , keep the temperature constant, stir magnetically for 2h to get 2-methyl-4-nitroacetanilide; add 15mL hydrogen peroxide and 7g sodium perborate to the above-mentioned 2-methyl-4-nitroacetanilide respectively. 2 hours at 300°C and 3MPa pressure, then add 20mL of acetic acid, cool down to 70°C, stir for 50min, put in ice water for 5min after stirring, and wash with deionized water to get 2-methyl -4-nitrophenylacetamide; finally the 2-methyl-4-nitrophenylacetamide obtained above is put into a 100mL reaction flask, and 5g potassium permanganate and 20mL sodium hypochlorite are added thereto respectively, at a temperature of 80 ℃, at a rotation speed of 900r/min, stir for 40min, and slowly add 20mL of hydrochloric acid with a mass fraction of 30% dropwise during the stirring process. - Nitrobenzoic acid. The method has the advantages of simple synthesis process, low cost and few by-products; the yield of the obtained product is as high as 97.5%, and the purity is as high as 99.36%.

Claims (1)

1. a synthetic method of 2-methyl-4-nitrobenzoic acid is characterized in that concrete synthetic steps are: (1) Take 5-10mL of nitric acid with a mass fraction of 69% and 3-5mL of sulfuric acid with a mass fraction of 98%, put them into a reaction vessel, control the temperature at 60-65°C, and the speed at 100-200r/min, stir and mix, After the mixed acid is cooled to 20°C, slowly add 30-40mL of toluene dropwise at the rate of each drop/5s, stir for 20-30min, put it in a hot water bath for 40-45min, then filter while it is hot, and pour the filtrate into cold water Cool to room temperature, wash with 20-40mL sodium bicarbonate solution until alkaline, and then rinse with water to obtain 2,5-dinitrotoluene; (2) Add 20-40g tin dichloride and 3-5g iron powder to the above-mentioned 2,5-dinitrotoluene, and add 20-30mL glacial acetic acid at the same time, set the speed at 500-700r/min, stir for 20 ~30min, after the stirring is completed, control the temperature at 80~85°C, add 10~20mL of hydrochloric acid with a mass fraction of 35% dropwise, increase the speed to 900~1200r/min, and stir for 30~50min to obtain 2-amino- 5-nitrotoluene; (3) Take 20-30mL of the 2-amino-5-nitrotoluene obtained above into a 70mL three-necked flask, add 15-20mL of acetic acid into it, control the temperature at 50-60°C, stir for 30-50min, and pour to Add 10-15 mL of sulfuric acid with a mass fraction of 98% dropwise, keep the temperature constant, and stir magnetically for 1-2 hours to obtain 2-methyl-4-nitroacetanilide; (4) Add 10-15mL of hydrogen peroxide and 5-7g of sodium perborate to the 2-methyl-4-nitroacetanilide obtained above, and react at a temperature of 200-300°C and a pressure of 1-3MPa for 1- 2h, then add 15-20mL acetic acid to it, lower the temperature to 60-70°C, stir for 30-50min, after the stirring is completed, place in ice water for 3-5min, wash with deionized water to get 2-methyl-4 - nitrophenylacetamide; (5) Put the 2-methyl-4-nitrophenylacetamide obtained above into an 80-100mL reaction bottle, add 3-5g of potassium permanganate and 15-20mL of sodium hypochlorite to it respectively, at a temperature of 70- 80°C, at a speed of 800-900r/min, stir for 30-40min, slowly add 10-20mL of hydrochloric acid with a mass fraction of 30% dropwise during the stirring process, after the dropwise addition is completed, react for 1-2h, and stand for suction filtration , and dried to give 2-methyl-4-nitrobenzoic acid.