Method for synthesizing 6-methoxy-2-naphthaldehyde

Abstract

The present invention discloses a method for synthesizing 6-methoxy-2-naphthaldehyde. The method comprises allowing bromization and reduction reaction of 2-methoxynaphthalene to produce 6-bromo-2-methoxynaphthalene, and allowing reaction of 6-bromo-2-methoxynaphthalene and N,N-dimethylformamide to obtain the final product. The method has no need for column chromatography to obtain high-purity 6-methoxy-2-naphthaldehyde, and improves yield.

Description

technical field

[0001] The invention relates to the field of chemical industry, in particular to a method for synthesizing 6-methoxy-2-naphthaldehyde. Background technique

[0002] 6-Methoxy-2-naphthaldehyde is a key intermediate of non-steroidal anti-inflammatory drug-nabumetone. Nabumetone, also known as Relifine, is a non-steroidal anti-inflammatory drug that was launched in the early 1980s. It is used to treat rheumatoid arthritis, osteoarthritis, etc., and other similar symptoms that require anti-inflammatory treatment. Its unique pharmacokinetic characteristics and good safety make it one of the most widely used non-steroidal anti-inflammatory drugs in the world.

[0003] In recent years, the methods for synthesizing 6-methoxy-2-naphthaldehyde mainly include:

[0004] 1) 6-methoxy-2-naphthoic acid is obtained by the esterification reaction of 6-methoxy-2-naphthoic acid and dimethyl sulfate, and then reacted with hydrazine hydrate to obtain 6-methoxy-2-naphthalene Fo...

Examples

Embodiment Construction

[0020] A kind of synthetic method of 6-methoxy-2-naphthalene formaldehyde, 2-methoxynaphthalene generates 6-bromo-2-methoxynaphthalene through bromination reaction and reduction reaction, it is characterized in that, described 6 -Bromo-2-methoxynaphthalene reacts with N,N-dimethylformamide to synthesize said 6-methoxy-2-naphthylcarbaldehyde.

[0021] (1) Synthesis of 6-bromo-2-methoxynaphthalene (4)

[0022] Add 20 mL of glacial acetic acid into a 200 mL three-necked flask, and add 5 g (31.6 mmol) of 2-methoxynaphthalene under mechanical stirring. Cool in an ice bath, control the reaction temperature below 30°C, slowly add a mixture of 10 g (63.2 mmol) of bromine (63.2 mmol) and 10 mL of glacial acetic acid to the reaction solution dropwise, and stir at room temperature for 1 h after the addition is complete.

[0023] Add 15mL of water to the above reaction solution, start to slowly heat to reflux, add 5.5g of tin powder (46.2mmol) in batches, then continue to reflux for 2-3h...

technical field

[0001] The invention relates to the field of chemical industry, in particular to a method for synthesizing 6-methoxy-2-naphthaldehyde. Background technique

[0002] 6-Methoxy-2-naphthaldehyde is a key intermediate of non-steroidal anti-inflammatory drug-nabumetone. Nabumetone, also known as Relifine, is a non-steroidal anti-inflammatory drug that was launched in the early 1980s. It is used to treat rheumatoid arthritis, osteoarthritis, etc., and other similar symptoms that require anti-inflammatory treatment. Its unique pharmacokinetic characteristics and good safety make it one of the most widely used non-steroidal anti-inflammatory drugs in the world.

[0003] In recent years, the methods for synthesizing 6-methoxy-2-naphthaldehyde mainly include:

[0004] 1) 6-methoxy-2-naphthoic acid is obtained by the esterification reaction of 6-methoxy-2-naphthoic acid and dimethyl sulfate, and then reacted with hydrazine hydrate to obtain 6-methoxy-2-naphthalene Fo...

Examples

Embodiment Construction

[0020] A kind of synthetic method of 6-methoxy-2-naphthalene formaldehyde, 2-methoxynaphthalene generates 6-bromo-2-methoxynaphthalene through bromination reaction and reduction reaction, it is characterized in that, described 6 -Bromo-2-methoxynaphthalene reacts with N,N-dimethylformamide to synthesize said 6-methoxy-2-naphthylcarbaldehyde.

[0021] (1) Synthesis of 6-bromo-2-methoxynaphthalene (4)

[0022] Add 20 mL of glacial acetic acid into a 200 mL three-necked flask, and add 5 g (31.6 mmol) of 2-methoxynaphthalene under mechanical stirring. Cool in an ice bath, control the reaction temperature below 30°C, slowly add a mixture of 10 g (63.2 mmol) of bromine (63.2 mmol) and 10 mL of glacial acetic acid to the reaction solution dropwise, and stir at room temperature for 1 h after the addition is complete.

[0023] Add 15mL of water to the above reaction solution, start to slowly heat to reflux, add 5.5g of tin powder (46.2mmol) in batches, then continue to reflux for 2-3h...