Synthetic method of ethyl p-aminobenzoate

Abstract

The invention discloses a synthetic method of ethyl p-aminobenzoate, comprising the following steps: using alcohol to dissolve para amino benzoic acid, preparing a para amino benzoic acid solution with the mass fraction of 5-30 %, adding thionyl chloride dropwisely in the para amino benzoic acid solution at the temperature of 0-50 DEG C for esterification reaction for 4-10 hours, after adding dropwisely, heating until reflux; after the reaction ends, cooling the reaction materials, after the solid substance is dissolved out, carrying out filtering, using water to dissolve the solid substance, adding weak base to neutralize the pH to 7-8, after the solid substance is dissolved out, carrying out filtering again, and then washing and drying to obtain the product of ethyl p-aminobenzoate. The method adopts para amino benzoic acid as raw material, uses thionyl chloride as desiccant for esterification reaction to prepare ethyl p-aminobenzoate, the advantages of rapid reaction speed, high yield, and high product purity are achieved, and the method has a good application prospect in industry.

Description

technical field

[0001] The invention relates to an esterification method of an amino-containing organic acid, in particular to a synthesis method for preparing ethyl p-aminobenzoate from p-aminobenzoic acid. Background technique

[0002] Ethyl p-aminobenzoate (Benzocaine, also known as benzocaine) is a colorless, odorless, tasteless crystal, insoluble in water, easily soluble in alcohol, ether, and chloroform. Ethyl p-aminobenzoate can be used as a local anesthetic for the skin and mucous membranes, as well as a protective agent for shading the sun, and it is also an intermediate for cough suppressants.

[0003] There are currently two main production methods for the synthesis of ethyl p-aminobenzoate. One method is to use p-nitrobenzoic acid as a raw material, and use sulfuric acid as a catalyst to carry out esterification with ethanol to obtain ethyl p-nitrobenzoate, and then reduce it with iron powder to obtain ethyl p-aminobenzoate. Another method is to use p-aminobenz...

Examples

Embodiment 1

[0017] In a 2000ml four-necked flask equipped with stirring, a thermometer and a condenser, add 274g of p-aminobenzoic acid, 1500ml of absolute ethanol, 160ml of thionyl chloride into a 250ml constant pressure separatory funnel, start stirring and cool down to 10°C, slowly Add thionyl chloride dropwise, control the temperature of the reaction solution at 8-14°C, connect the condenser tube to the tail gas absorption device, finish adding thionyl chloride in 4 hours, and start to slowly heat up to reflux under the protection of nitrogen, and the reaction solution gradually Silver-white flaky solids appear, reflux temperature is 74-78°C, reflux time is 6.5 hours, cool down and filter, wash the solid once with absolute ethanol, dissolve it with deionized water, adjust the pH to 7-8 with 10% sodium carbonate aqueous solution, filter and wash with water , Vacuum drying to obtain the product: 289g, purity (HPLC): 99.7%, melting point: 90-91°C, yield: 95.8%.

Embodiment 2

[0019] In a 2000ml four-necked flask equipped with stirring, a thermometer and a condenser, add 274g of p-aminobenzoic acid, 1500ml of absolute ethanol, and 140ml of thionyl chloride into a 250ml constant pressure separatory funnel, start stirring and cool down to 10°C, slowly Add thionyl chloride dropwise, control the temperature of the reaction solution at 8-10°C, connect the condensation pipe to the tail gas absorbing device, complete the thionyl chloride dropwise in 5 hours, then slowly heat up to reflux under the protection of nitrogen, and the reaction solution gradually A silver-white flaky solid appears, the reflux temperature is 70-75°C, the reflux time is 5 hours, the temperature is lowered and filtered, the solid is washed once with absolute ethanol, dissolved in deionized water, adjusted to pH 7-8 with 10% sodium bicarbonate aqueous solution, filtered, Washed with water and dried in vacuum to obtain the product: 270g, purity (HPLC): 99.7%, melting point: 90-91°C, yi...

Embodiment 3

[0021] In a 2000ml four-necked flask equipped with stirring, a thermometer and a condenser, add 274g of p-aminobenzoic acid, 1800ml of absolute ethanol, 150ml of thionyl chloride into a 250ml constant pressure separatory funnel, start stirring and cool down to 10°C, slowly Add thionyl chloride dropwise, control the temperature of the reaction solution at 8-14°C, connect the condenser tube to the tail gas absorption device, finish adding thionyl chloride in 4 hours, and start to slowly heat up to reflux under the protection of nitrogen, and the reaction solution gradually Silver-white flaky solid appears, reflux temperature is 72-78°C, reflux time is 6 hours, cool down and filter, wash the solid once with absolute ethanol, dissolve with deionized water, adjust pH to 7-8 with 10% sodium carbonate aqueous solution, filter and wash with water , Vacuum drying to obtain the product: 280g, purity (HPLC): 99.9%, melting point: 90-91°C, yield: 92.7%.

technical field

[0001] The invention relates to an esterification method of an amino-containing organic acid, in particular to a synthesis method for preparing ethyl p-aminobenzoate from p-aminobenzoic acid. Background technique

[0002] Ethyl p-aminobenzoate (Benzocaine, also known as benzocaine) is a colorless, odorless, tasteless crystal, insoluble in water, easily soluble in alcohol, ether, and chloroform. Ethyl p-aminobenzoate can be used as a local anesthetic for the skin and mucous membranes, as well as a protective agent for shading the sun, and it is also an intermediate for cough suppressants.

[0003] There are currently two main production methods for the synthesis of ethyl p-aminobenzoate. One method is to use p-nitrobenzoic acid as a raw material, and use sulfuric acid as a catalyst to carry out esterification with ethanol to obtain ethyl p-nitrobenzoate, and then reduce it with iron powder to obtain ethyl p-aminobenzoate. Another method is to use p-aminobenz...

Examples

Embodiment 1

[0017] In a 2000ml four-necked flask equipped with stirring, a thermometer and a condenser, add 274g of p-aminobenzoic acid, 1500ml of absolute ethanol, 160ml of thionyl chloride into a 250ml constant pressure separatory funnel, start stirring and cool down to 10°C, slowly Add thionyl chloride dropwise, control the temperature of the reaction solution at 8-14°C, connect the condenser tube to the tail gas absorption device, finish adding thionyl chloride in 4 hours, and start to slowly heat up to reflux under the protection of nitrogen, and the reaction solution gradually Silver-white flaky solids appear, reflux temperature is 74-78°C, reflux time is 6.5 hours, cool down and filter, wash the solid once with absolute ethanol, dissolve it with deionized water, adjust the pH to 7-8 with 10% sodium carbonate aqueous solution, filter and wash with water , Vacuum drying to obtain the product: 289g, purity (HPLC): 99.7%, melting point: 90-91°C, yield: 95.8%.

Embodiment 2

[0019] In a 2000ml four-necked flask equipped with stirring, a thermometer and a condenser, add 274g of p-aminobenzoic acid, 1500ml of absolute ethanol, and 140ml of thionyl chloride into a 250ml constant pressure separatory funnel, start stirring and cool down to 10°C, slowly Add thionyl chloride dropwise, control the temperature of the reaction solution at 8-10°C, connect the condensation pipe to the tail gas absorbing device, complete the thionyl chloride dropwise in 5 hours, then slowly heat up to reflux under the protection of nitrogen, and the reaction solution gradually A silver-white flaky solid appears, the reflux temperature is 70-75°C, the reflux time is 5 hours, the temperature is lowered and filtered, the solid is washed once with absolute ethanol, dissolved in deionized water, adjusted to pH 7-8 with 10% sodium bicarbonate aqueous solution, filtered, Washed with water and dried in vacuum to obtain the product: 270g, purity (HPLC): 99.7%, melting point: 90-91°C, yi...

Embodiment 3

[0021] In a 2000ml four-necked flask equipped with stirring, a thermometer and a condenser, add 274g of p-aminobenzoic acid, 1800ml of absolute ethanol, 150ml of thionyl chloride into a 250ml constant pressure separatory funnel, start stirring and cool down to 10°C, slowly Add thionyl chloride dropwise, control the temperature of the reaction solution at 8-14°C, connect the condenser tube to the tail gas absorption device, finish adding thionyl chloride in 4 hours, and start to slowly heat up to reflux under the protection of nitrogen, and the reaction solution gradually Silver-white flaky solid appears, reflux temperature is 72-78°C, reflux time is 6 hours, cool down and filter, wash the solid once with absolute ethanol, dissolve with deionized water, adjust pH to 7-8 with 10% sodium carbonate aqueous solution, filter and wash with water , Vacuum drying to obtain the product: 280g, purity (HPLC): 99.9%, melting point: 90-91°C, yield: 92.7%.