Green preparation process of benzocaine

Abstract

The invention discloses a green preparation process of benzocaine. The process comprises the steps that p-nitrobenzoic acid and ethanol are subjected to esterification under the catalysis of concentrated sulfuric acid to obtain ethyl p-nitrobenzoate; ethyl p-nitrobenzoate is subjected to catalytic hydrogenation to obtain the benzocaine, wherein catalytic hydrogenation reaction is performed in water; the catalytic hydrogenation reaction temperature is 90 to 110 DEG C; the catalytic hydrogenation reaction pressure is 0.2 to 1.0MPa; the use quantity of water is 3 to 7 times of the weight of ethylp-nitrobenzoate; the weight ratio of ethyl p-nitrobenzoate to a catalyst is (1:0.001)-(1:0.1); the catalyst is a Pd / C catalyst with the mass fraction being 3 to 10 weight percent. Through the catalytic hydrogenation reaction, the use of organic solvents is avoided, so that the whole benzocaine preparation becomes a green process; the proper use quantity of water is selected, so that high reactionyield and product purity can be obtained.

Description

Technical field

[0001] The invention belongs to the technical field of fine chemicals, and specifically relates to a green preparation process of benzocaine (ethyl para-aminobenzoate). Background technique

[0002] Benzocaine (Benzocaine) is another name for ethyl para-aminobenzoate. It can be used as a local anesthetic for wounds, ulcers and hemorrhoids to relieve itching and pain. It can also be used as a drug intermediate; UV absorbers can be used It is mainly used in sunscreen and tanning cosmetics. It is chemically stable to light and air, safe to the skin, and has the ability to form a film on the skin. At the same time, it can be used as an intermediate for other ultraviolet absorbers.

[0003] Chinese patent document CN105315168A discloses a green preparation process of N-(4-ethoxycarbonylphenyl)-N'-methyl-N'-phenylformamidine intermediate (also known as benzocaine), which Using p-nitrobenzoic acid as a raw material, it is firstly esterified with ethanol under the catalysi...

Examples

Embodiment 1）

[0019] The green preparation process of benzocaine in this embodiment has the following steps:

[0020] ① Add 80g of commercially available absolute ethanol (1.74mol) and 50g of p-nitrobenzoic acid (0.30mol) into the reaction device under stirring, and then slowly add dropwise 10g of dehydrated concentrated sulfuric acid (0.10mol) [ Refer to Chinese Patent Document CN105315168A Example 1], 15 minutes of dripping, after dripping, stir and raise the temperature to 80±2°C, reflux for 6h.

[0021] After the reaction, the ethanol is distilled out under normal pressure. When the temperature reaches 100±2°C, the heating is stopped, and the upper layer material (concentrated sulfuric acid layer) is applied to the next batch.

[0022] Cool the lower layer material to 60±2°C, adjust the pH to 8 with a 5wt% sodium carbonate aqueous solution, re-measure the pH after stirring for 0.5h, and stand still for layering.

[0023] ②Control the temperature of the lower layer material (about 58g) to 60±2℃,...

Embodiment 2～ Embodiment 5）

[0025] Step ① of each embodiment is the same as that of embodiment 1, and the difference lies in step ②. See Table 1 for details.

[0026] Table 1

[0027]

Technical field

[0001] The invention belongs to the technical field of fine chemicals, and specifically relates to a green preparation process of benzocaine (ethyl para-aminobenzoate). Background technique

[0002] Benzocaine (Benzocaine) is another name for ethyl para-aminobenzoate. It can be used as a local anesthetic for wounds, ulcers and hemorrhoids to relieve itching and pain. It can also be used as a drug intermediate; UV absorbers can be used It is mainly used in sunscreen and tanning cosmetics. It is chemically stable to light and air, safe to the skin, and has the ability to form a film on the skin. At the same time, it can be used as an intermediate for other ultraviolet absorbers.

[0003] Chinese patent document CN105315168A discloses a green preparation process of N-(4-ethoxycarbonylphenyl)-N'-methyl-N'-phenylformamidine intermediate (also known as benzocaine), which Using p-nitrobenzoic acid as a raw material, it is firstly esterified with ethanol under the catalysi...

Examples

Embodiment 1）

[0019] The green preparation process of benzocaine in this embodiment has the following steps:

[0020] ① Add 80g of commercially available absolute ethanol (1.74mol) and 50g of p-nitrobenzoic acid (0.30mol) into the reaction device under stirring, and then slowly add dropwise 10g of dehydrated concentrated sulfuric acid (0.10mol) [ Refer to Chinese Patent Document CN105315168A Example 1], 15 minutes of dripping, after dripping, stir and raise the temperature to 80±2°C, reflux for 6h.

[0021] After the reaction, the ethanol is distilled out under normal pressure. When the temperature reaches 100±2°C, the heating is stopped, and the upper layer material (concentrated sulfuric acid layer) is applied to the next batch.

[0022] Cool the lower layer material to 60±2°C, adjust the pH to 8 with a 5wt% sodium carbonate aqueous solution, re-measure the pH after stirring for 0.5h, and stand still for layering.

[0023] ②Control the temperature of the lower layer material (about 58g) to 60±2℃,...

Embodiment 2～ Embodiment 5）

[0025] Step ① of each embodiment is the same as that of embodiment 1, and the difference lies in step ②. See Table 1 for details.

[0026] Table 1

[0027]