Synthesis method of 3,5-dimethyl-4-nitropyridine-N-oxide

Abstract

The invention discloses a synthesis method of 3,5-dimethyl-4-nitropyridine-N-oxide, and belongs to the field of chemical industry. The method comprises the following steps: mixing 3,5-dimethyl pyridine-N-oxide with concentrated sulfuric acid so as to form a mixed liquid, dropwise adding a sulfuric acid solution of potassium nitrate to the mixed liquid at 0-60 DEG C, and reacting at 60-120 DEG C for 0.5-12hr so as to obtain 3,5-dimethyl-4-nitropyridine-N-oxide. The synthesis method of the 3,5-dimethyl-4-nitropyridine-N-oxide, by replacing concentrated nitric acid or fuming nitric acid with the potassium nitrate as a nitrating reagent, can be used for greatly shortening reaction time and avoiding the generation of brown smoke during reacting and post-processing, an operating environment is friendly, and the problem of environmental pollution caused by the massive use of nitric acid is relieved; and meanwhile, reaction yield is improved as well; since environmental issue is increasingly emphasized nowadays, the 3,5-dimethyl-4-nitropyridine-N-oxide can be used for better replacing nitric acid as a nitrating reagent to complete a nitrating reaction.

Description

technical field

[0001] The invention belongs to the field of chemical industry, and in particular relates to a synthesis method of 3,5-dimethyl-4-nitropyridine-N-oxide. Background technique

[0002] 3,5-Dimethyl-4-nitropyridine-N-oxide is an important pharmaceutical intermediate, which can be used to synthesize omeprazole and esomeprazole. Use 3,5-lutidine as the starting material, add hydrogen peroxide and a suitable catalyst to obtain 3,5-lutidine-N-oxide, then add concentrated nitric acid / sulfuric acid or fuming nitric acid / sulfuric acid as a mixed acid The nitrating reagent can be used to produce 3,5-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 ...

Examples

Embodiment 1

[0022] Dissolve 12.3g of 3,5-lutidine-N-oxide in 90g of concentrated sulfuric acid, add dropwise a sulfuric acid solution of potassium nitrate (potassium nitrate 14.15g, concentrated sulfuric acid 100g ). After the dropwise addition was completed, the reaction was carried out at a temperature of 60° C. to 65° C. for 2 hours. HPLC monitoring until complete reaction of starting material. Cool down to room temperature, add water and stir, adjust pH to 8-8.5 with ammonia water, filter and dry to obtain 14.4 g of light yellow 3,5-dimethyl-4-nitropyridine-N-oxide, HPLC purity 99%, yield The rate is 85.7%.

Embodiment 2

[0024] Dissolve 12.3g of 3,5-lutidine-N-oxide in 188g of concentrated sulfuric acid, add dropwise a sulfuric acid solution of potassium nitrate (40.44g of potassium nitrate, 600g of concentrated sulfuric acid) at a temperature of 20°C to 30°C ). 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 and stir, adjust the pH to 8-8.5 with ammonia water, filter, and dry to obtain 14.5 g of light yellow 3,5-dimethyl-4-nitropyridine-N-oxide, HPLC purity 99%. The yield is 86.3%.

Embodiment 3

[0026] Dissolve 12.3g of 3,5-lutidine-N-oxide in 65g of concentrated sulfuric acid, and dropwise add sulfuric acid solution of potassium nitrate (potassium nitrate 10.11g, concentrated sulfuric acid 60g) at a temperature of 10°C to 15°C ). 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 and stir, adjust pH to 8-8.5 with ammonia water, filter and dry to obtain 14.3 g of light yellow 3,5-dimethyl-4-nitropyridine-N-oxide, HPLC purity 99%, yield rate of 85%.

technical field

[0001] The invention belongs to the field of chemical industry, and in particular relates to a synthesis method of 3,5-dimethyl-4-nitropyridine-N-oxide. Background technique

[0002] 3,5-Dimethyl-4-nitropyridine-N-oxide is an important pharmaceutical intermediate, which can be used to synthesize omeprazole and esomeprazole. Use 3,5-lutidine as the starting material, add hydrogen peroxide and a suitable catalyst to obtain 3,5-lutidine-N-oxide, then add concentrated nitric acid / sulfuric acid or fuming nitric acid / sulfuric acid as a mixed acid The nitrating reagent can be used to produce 3,5-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 ...

Examples

Embodiment 1

[0022] Dissolve 12.3g of 3,5-lutidine-N-oxide in 90g of concentrated sulfuric acid, add dropwise a sulfuric acid solution of potassium nitrate (potassium nitrate 14.15g, concentrated sulfuric acid 100g ). After the dropwise addition was completed, the reaction was carried out at a temperature of 60° C. to 65° C. for 2 hours. HPLC monitoring until complete reaction of starting material. Cool down to room temperature, add water and stir, adjust pH to 8-8.5 with ammonia water, filter and dry to obtain 14.4 g of light yellow 3,5-dimethyl-4-nitropyridine-N-oxide, HPLC purity 99%, yield The rate is 85.7%.

Embodiment 2

[0024] Dissolve 12.3g of 3,5-lutidine-N-oxide in 188g of concentrated sulfuric acid, add dropwise a sulfuric acid solution of potassium nitrate (40.44g of potassium nitrate, 600g of concentrated sulfuric acid) at a temperature of 20°C to 30°C ). 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 and stir, adjust the pH to 8-8.5 with ammonia water, filter, and dry to obtain 14.5 g of light yellow 3,5-dimethyl-4-nitropyridine-N-oxide, HPLC purity 99%. The yield is 86.3%.

Embodiment 3

[0026] Dissolve 12.3g of 3,5-lutidine-N-oxide in 65g of concentrated sulfuric acid, and dropwise add sulfuric acid solution of potassium nitrate (potassium nitrate 10.11g, concentrated sulfuric acid 60g) at a temperature of 10°C to 15°C ). 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 and stir, adjust pH to 8-8.5 with ammonia water, filter and dry to obtain 14.3 g of light yellow 3,5-dimethyl-4-nitropyridine-N-oxide, HPLC purity 99%, yield rate of 85%.

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