Preparation method of 2-pyridine carboxaldehyde

Abstract

The invention provides a preparation method of 2-pyridine carboxaldehyde, which comprises the following steps of: (1) carrying out the temperature rise reflux reaction of 2-methylpyridine in the presence of halohydrocarbon used as a solvent, benzoyl amide used as a catalyst and trichloro isocyanate used as a chlorinating agent to obtain 2-chloromethyl pyridine; (2) carrying out hydrolysis on 2-chloromethyl pyridine under the alkalinity condition and rising the temperature to obtain 2-pyridinemethanol; (3) cooling 2-pyridinemethanol to -10-0 DEG C in presence of halohydrocarbon used as a solvent and 2,2,6,6-tetramethylpiperidine nitric oxide and potassium bromide used as catalysts, dipping 10 percent by weight of sodium hypochlorite solution used as a oxidizing agent, and keeping the temperature at 10-25 DEG C after the dipping to obtain 2-pyridine carboxaldehyde. The preparation method provided by the invention has the advantages of high yield, low cost, mild reaction condition and easy industrialization production.

Description

technical field

[0001] The invention belongs to the field of organic chemistry, in particular to a new preparation method of 2-pyridinecarbaldehyde. Background technique

[0002] As an important pharmaceutical intermediate and fine chemical raw material, 2-pyridinecarbaldehyde has a wide range of applications and a broad market prospect. In medicine, 2-pyridinecarbaldehyde, as an important pharmaceutical intermediate, can be used to synthesize the laxative bisacodyl, and it is also a raw material for the synthesis of organophosphate antidote pralidoxime, and it has recently been reported that 2-pyridinecarbaldehyde can also be used as a synthetic Raw material for anti-HIV protease inhibitors; in agriculture, 2-pyridinecarbaldehyde is an essential intermediate for the synthesis of some acaricides; in the photosensitive industry, 2-pyridinecarbaldehyde can be used to synthesize nitrogen-containing heterocyclic color photographic materials. Therefore, it has always been the di...

Examples

Embodiment 1

[0031] Embodiment 1: the preparation of 2-chloromethylpyridine (3)

[0032] In a 250 mL three-necked flask, 2-picoline (2) (33 g, 0.35 mol), chloroform (125 mL), and benzamide (1.5 g, 12.3 mmol) were sequentially added. Raise the temperature to reflux, add the chlorinating agent trichloroisocyanate (90g, 0.38mol) within 1h, continue to heat up to 40°C and reflux for 2h, track and analyze by thin-layer chromatography, when the reaction is completely converted into 2-chloromethylpyridine ,cool down. The reaction solution was filtered, the filter residue was washed with chloroform (2×100 mL), and the washings were combined. The organic phase was washed with saturated sodium carbonate solution, the layers were separated, the aqueous layer was extracted with chloroform (2×50 mL), the organic phases were combined, and the solvent was evaporated under reduced pressure to obtain 42.4 g of 2-chloromethylpyridine (3), with a yield of 95% . 1 HNMR (400MHz, CDCl 3 ): δ5.8 (s, 2H), 7.3...

Embodiment 2

[0033] Embodiment 2: the preparation of 2-chloromethylpyridine (3)

[0034] In a 250 mL three-necked flask, 2-picoline (2) (33 g, 0.35 mol), dichloromethane (125 mL), and benzamide (1.5 g, 12.3 mmol) were sequentially added. Raise the temperature to reflux, add the chlorinating agent trichloroisocyanate (90g, 0.38mol) within 1h, continue to heat up to 90°C and reflux for 2.5h, follow up and analyze by thin layer chromatography, until the reaction is completely converted into 2-chloromethylpyridine , cool down. The reaction solution was filtered, the filter residue was washed with chloroform (2×100 mL), and the washings were combined. The organic phase was washed with saturated sodium carbonate solution, the layers were separated, the aqueous layer was extracted with dichloromethane (2×50 mL), the organic phases were combined, and the solvent was evaporated under reduced pressure to obtain 42.3 g of 2-chloromethylpyridine (3). The yield was 94%. 1 HNMR (400MHz, CDCl 3 ): δ5...

Embodiment 3

[0035] Embodiment 3: the preparation of 2-chloromethylpyridine (3)

[0036] In a 250 mL three-necked flask, 2-picoline (2) (33 g, 0.35 mol), 1,2-dichloroethane (125 mL), and benzamide (1.5 g, 12.3 mmol) were sequentially added. Raise the temperature to reflux, add the chlorinating agent trichloroisocyanate (90g, 0.38mol) within 1h, continue to heat up to 60°C and reflux for 3h, follow up and analyze by thin layer chromatography, when the reaction is completely converted into 2-chloromethylpyridine ,cool down. The reaction solution was filtered, the filter residue was washed with chloroform (2×100 mL), and the washings were combined. The organic phase was washed with saturated sodium carbonate solution, the layers were separated, the aqueous layer was extracted with chloroform (2×50 mL), the organic phases were combined, and the solvent was evaporated under reduced pressure to obtain 40.1 g of 2-chloromethylpyridine (3), with a yield of 90% . 1 HNMR (400MHz, CDCl 3 ): δ5.8 ...

technical field

[0001] The invention belongs to the field of organic chemistry, in particular to a new preparation method of 2-pyridinecarbaldehyde. Background technique

[0002] As an important pharmaceutical intermediate and fine chemical raw material, 2-pyridinecarbaldehyde has a wide range of applications and a broad market prospect. In medicine, 2-pyridinecarbaldehyde, as an important pharmaceutical intermediate, can be used to synthesize the laxative bisacodyl, and it is also a raw material for the synthesis of organophosphate antidote pralidoxime, and it has recently been reported that 2-pyridinecarbaldehyde can also be used as a synthetic Raw material for anti-HIV protease inhibitors; in agriculture, 2-pyridinecarbaldehyde is an essential intermediate for the synthesis of some acaricides; in the photosensitive industry, 2-pyridinecarbaldehyde can be used to synthesize nitrogen-containing heterocyclic color photographic materials. Therefore, it has always been the di...

Examples

Embodiment 1

[0031] Embodiment 1: the preparation of 2-chloromethylpyridine (3)

[0032] In a 250 mL three-necked flask, 2-picoline (2) (33 g, 0.35 mol), chloroform (125 mL), and benzamide (1.5 g, 12.3 mmol) were sequentially added. Raise the temperature to reflux, add the chlorinating agent trichloroisocyanate (90g, 0.38mol) within 1h, continue to heat up to 40°C and reflux for 2h, track and analyze by thin-layer chromatography, when the reaction is completely converted into 2-chloromethylpyridine ,cool down. The reaction solution was filtered, the filter residue was washed with chloroform (2×100 mL), and the washings were combined. The organic phase was washed with saturated sodium carbonate solution, the layers were separated, the aqueous layer was extracted with chloroform (2×50 mL), the organic phases were combined, and the solvent was evaporated under reduced pressure to obtain 42.4 g of 2-chloromethylpyridine (3), with a yield of 95% . 1 HNMR (400MHz, CDCl 3 ): δ5.8 (s, 2H), 7.3...

Embodiment 2

[0033] Embodiment 2: the preparation of 2-chloromethylpyridine (3)

[0034] In a 250 mL three-necked flask, 2-picoline (2) (33 g, 0.35 mol), dichloromethane (125 mL), and benzamide (1.5 g, 12.3 mmol) were sequentially added. Raise the temperature to reflux, add the chlorinating agent trichloroisocyanate (90g, 0.38mol) within 1h, continue to heat up to 90°C and reflux for 2.5h, follow up and analyze by thin layer chromatography, until the reaction is completely converted into 2-chloromethylpyridine , cool down. The reaction solution was filtered, the filter residue was washed with chloroform (2×100 mL), and the washings were combined. The organic phase was washed with saturated sodium carbonate solution, the layers were separated, the aqueous layer was extracted with dichloromethane (2×50 mL), the organic phases were combined, and the solvent was evaporated under reduced pressure to obtain 42.3 g of 2-chloromethylpyridine (3). The yield was 94%. 1 HNMR (400MHz, CDCl 3 ): δ5...

Embodiment 3

[0035] Embodiment 3: the preparation of 2-chloromethylpyridine (3)

[0036] In a 250 mL three-necked flask, 2-picoline (2) (33 g, 0.35 mol), 1,2-dichloroethane (125 mL), and benzamide (1.5 g, 12.3 mmol) were sequentially added. Raise the temperature to reflux, add the chlorinating agent trichloroisocyanate (90g, 0.38mol) within 1h, continue to heat up to 60°C and reflux for 3h, follow up and analyze by thin layer chromatography, when the reaction is completely converted into 2-chloromethylpyridine ,cool down. The reaction solution was filtered, the filter residue was washed with chloroform (2×100 mL), and the washings were combined. The organic phase was washed with saturated sodium carbonate solution, the layers were separated, the aqueous layer was extracted with chloroform (2×50 mL), the organic phases were combined, and the solvent was evaporated under reduced pressure to obtain 40.1 g of 2-chloromethylpyridine (3), with a yield of 90% . 1 HNMR (400MHz, CDCl 3 ): δ5.8 ...

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