A kind of synthetic method of 2,3-dimethyl-4-nitropyridine-n-oxide

Abstract

The invention discloses a synthesis method of 2,3-dimethyl-4-nitropyridine-N-oxide, which belongs to the field of chemical industry. The synthesis method is to mix 2,3-lutidine-N-oxide and concentrated sulfuric acid to form a mixed solution, and add the sulfuric acid solution of potassium nitrate dropwise to the in the mixed solution; after the dropwise addition, react at a temperature of 80°C to 120°C. The synthesis method uses potassium nitrate as a nitrating reagent instead of concentrated nitric acid or fuming nitric acid, the reaction time is greatly shortened, no brownish-yellow smoke is produced in the reaction and post-treatment process, the operation environment is friendly, and the environmental pollution caused by a large amount of nitric acid is reduced. At the same time, the reaction yield has also been improved. Today, as environmental issues are getting more and more attention, it can be a good substitute for nitric acid as a nitrating reagent to complete the nitration reaction.

Description

technical field

[0001] The invention belongs to the field of chemical industry, and in particular relates to a synthesis method of 2,3-dimethyl-4-nitropyridine-N-oxide. Background technique

[0002] 2,3-Dimethyl-4-nitropyridine-N-oxide is an important pharmaceutical intermediate, which can be used to synthesize lansoprazole and rabeprazole. Use 2,3-lutidine as the starting material, add hydrogen peroxide and a suitable catalyst to obtain 2,3-lutidine-N-oxide, and then nitrate with concentrated nitric acid / sulfuric acid or fuming nitric acid. Sulfuric acid as a mixed acid Reagent to produce 2,3-dimethyl-4-nitropyridine-N-oxide.

[0003] Concentrated sulfuric acid plays a catalytic and dehydrating role in the nitration reaction. When the concentrated nitric acid of 65%~68% is adopted as the nitrating reagent, due to the high water content in the concentrated nitric acid, the reaction is affected in the presence of water, resulting in a decrease in the yield and a decrease in...

Examples

Embodiment 1

[0020] Dissolve 12.3g of 2,3-lutidine-N-oxide in 92g of concentrated sulfuric acid (mass concentration: 98%), and add potassium nitrate sulfuric acid dropwise at a temperature of -10°C to -5°C solution (14.15 g of potassium nitrate, 100 g of concentrated sulfuric acid with a mass concentration of 98%). After the dropwise addition was completed, the reaction was carried out at a temperature of 80° C. to 85° C. for 2 hours. HPLC monitoring until complete reaction of starting material. Cool down to room temperature, add water, stir, and filter. The filtrate was extracted three times with dichloromethane, and the organic phase was concentrated to obtain 15.6 g of light yellow 2,3-dimethyl-4-nitropyridine-N-oxide, with an HPLC purity of 99% and a yield of 92.9%.

Embodiment 2

[0022] 12.3g of 2,3-lutidine-N-oxide was dissolved in 188g of concentrated sulfuric acid (98% mass concentration), and the sulfuric acid solution of potassium nitrate (nitric acid Potassium 40.44g, mass concentration is 98% concentrated sulfuric acid 600g). After the dropwise addition was completed, the reaction was carried out at a temperature of 110° C. to 120° C. for 0.5 hours. HPLC monitoring until complete reaction of starting material. Cool down to room temperature, add water, stir, and filter. The filtrate was extracted three times with dichloromethane, and the organic phase was concentrated to obtain 15.5 g of light yellow 2,3-dimethyl-4-nitropyridine-N-oxide, with an HPLC purity of 99% and a yield of 92.3%.

Embodiment 3

[0024] Dissolve 12.3g of 2,3-lutidine-N-oxide in 65g of concentrated sulfuric acid (mass concentration is 98%), add dropwise sulfuric acid solution of potassium nitrate (nitric acid Potassium 10.11g, mass concentration is 98% concentrated sulfuric acid 60g). After the dropwise addition is completed, the reaction is carried out at a temperature of 85° C. to 90° C. for 1 hour. HPLC monitoring until complete reaction of starting material. Cool down to room temperature, add water, stir, and filter. The filtrate was extracted three times with dichloromethane, and the organic phase was concentrated to obtain 15.3 g of light yellow 2,3-dimethyl-4-nitropyridine-N-oxide, with a HPLC purity of 99% and a yield of 91.1%.

technical field

[0001] The invention belongs to the field of chemical industry, and in particular relates to a synthesis method of 2,3-dimethyl-4-nitropyridine-N-oxide. Background technique

[0002] 2,3-Dimethyl-4-nitropyridine-N-oxide is an important pharmaceutical intermediate, which can be used to synthesize lansoprazole and rabeprazole. Use 2,3-lutidine as the starting material, add hydrogen peroxide and a suitable catalyst to obtain 2,3-lutidine-N-oxide, and then nitrate with concentrated nitric acid / sulfuric acid or fuming nitric acid. Sulfuric acid as a mixed acid Reagent to produce 2,3-dimethyl-4-nitropyridine-N-oxide.

[0003] Concentrated sulfuric acid plays a catalytic and dehydrating role in the nitration reaction. When the concentrated nitric acid of 65%~68% is adopted as the nitrating reagent, due to the high water content in the concentrated nitric acid, the reaction is affected in the presence of water, resulting in a decrease in the yield and a decrease in...

Examples

Embodiment 1

[0020] Dissolve 12.3g of 2,3-lutidine-N-oxide in 92g of concentrated sulfuric acid (mass concentration: 98%), and add potassium nitrate sulfuric acid dropwise at a temperature of -10°C to -5°C solution (14.15 g of potassium nitrate, 100 g of concentrated sulfuric acid with a mass concentration of 98%). After the dropwise addition was completed, the reaction was carried out at a temperature of 80° C. to 85° C. for 2 hours. HPLC monitoring until complete reaction of starting material. Cool down to room temperature, add water, stir, and filter. The filtrate was extracted three times with dichloromethane, and the organic phase was concentrated to obtain 15.6 g of light yellow 2,3-dimethyl-4-nitropyridine-N-oxide, with an HPLC purity of 99% and a yield of 92.9%.

Embodiment 2

[0022] 12.3g of 2,3-lutidine-N-oxide was dissolved in 188g of concentrated sulfuric acid (98% mass concentration), and the sulfuric acid solution of potassium nitrate (nitric acid Potassium 40.44g, mass concentration is 98% concentrated sulfuric acid 600g). After the dropwise addition was completed, the reaction was carried out at a temperature of 110° C. to 120° C. for 0.5 hours. HPLC monitoring until complete reaction of starting material. Cool down to room temperature, add water, stir, and filter. The filtrate was extracted three times with dichloromethane, and the organic phase was concentrated to obtain 15.5 g of light yellow 2,3-dimethyl-4-nitropyridine-N-oxide, with an HPLC purity of 99% and a yield of 92.3%.

Embodiment 3

[0024] Dissolve 12.3g of 2,3-lutidine-N-oxide in 65g of concentrated sulfuric acid (mass concentration is 98%), add dropwise sulfuric acid solution of potassium nitrate (nitric acid Potassium 10.11g, mass concentration is 98% concentrated sulfuric acid 60g). After the dropwise addition is completed, the reaction is carried out at a temperature of 85° C. to 90° C. for 1 hour. HPLC monitoring until complete reaction of starting material. Cool down to room temperature, add water, stir, and filter. The filtrate was extracted three times with dichloromethane, and the organic phase was concentrated to obtain 15.3 g of light yellow 2,3-dimethyl-4-nitropyridine-N-oxide, with a HPLC purity of 99% and a yield of 91.1%.

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