Preparation method of chloro polyhydroxy aza-aromatic ring compound

Abstract

The invention discloses a preparation method of a chloro polyhydroxy aza-aromatic ring compound. With the olyhydroxy aza-aromatic ring compound as a raw material, with BTC and SOC12 as a dual-chlorination reagent, at the room temperature to the reaction backflow temperature, with 4-dimethylaminopyridine (DMAP) as a catalyst, a chlorination reaction is conducted for generating the chloro polyhydroxy aza-aromatic ring compound. The BTC / SOC12 / DMAP chlorination system has an efficient and high-selectivity chlorine-substitution function on the polyhydroxy aza-aromatic ring compound; the system canreplace POC13, and generation of phosphorus-containing wastewater is avoided. The BTC is used as the chlorination reagent, and reaction by-products are HC1 and CO2. By considering the aspects such asindustrial wastewater treatment and environment protection, the advantages of the method are obvious; after a reaction is completed, the evaporation amount of SOC12 is hardly reduced, repeated application can be achieved, and the technology cost is reduced.

Description

technical field

[0001] The invention belongs to the field of organic chemistry, in particular to a preparation method of chlorinated polyhydroxy nitrogen heteroaromatic ring compounds. Background technique

[0002] Chlorinated polyhydroxy azaaromatic compounds are useful as active ingredients in pharmaceuticals and other functional chemicals. As active intermediates, new carbon-carbon bonds and carbon-heterobonds can be formed through various reactions. Traditional methods for the synthesis of chlorinated polyhydroxyazaromatic compounds include the use of POCl 3 or PCl 5 Direct substitution of the hydroxyl groups of their corresponding compounds, these experimental conditions have changed little over the past 100 years, usually involving tertiary amines (or amides) as catalysts and the use of excess POCl 3 as a solvent. Due to the ever-increasing environmental requirements, the phosphorus oxychloride in the post-reaction treatment and the phosphorus-containing wastewater...

Examples

Embodiment 1

[0020] Add 1000 mg 2,4-dihydroxypyrimidine (8.9 mmol), 50 mg DMAP and 4 mL SOCl to a 50 mL reaction vial 2 , forming a cloudy solution. Slowly add 5.28g (17.8mmol) SOCl of BTC dropwise 2 (4 mL) solution. Heating in an oil bath, controlling the reaction temperature between 65°C and 70°C, and cooling the reflux reaction with refrigerated liquid. After reacting to the complete reaction of the raw materials, the reaction solution was cooled, evaporated to remove the solvent, added to 10 mL of ice water, neutralized with sodium carbonate solution to pH=8-9, extracted with dichloromethane, and the organic layer was separated. After washing with water and brine, and drying with anhydrous sodium sulfate, the solvent was evaporated (or chromatographic column) to obtain 2,4-dichloropyrimidine with a yield of 95%.

[0021] Examples 2-9 The same method as in Example 1 was used to prepare polychlorinated nitrogen heteroaromatic compounds, and the yields are listed in Table 1.

[0022] ...

technical field

[0001] The invention belongs to the field of organic chemistry, in particular to a preparation method of chlorinated polyhydroxy nitrogen heteroaromatic ring compounds. Background technique

[0002] Chlorinated polyhydroxy azaaromatic compounds are useful as active ingredients in pharmaceuticals and other functional chemicals. As active intermediates, new carbon-carbon bonds and carbon-heterobonds can be formed through various reactions. Traditional methods for the synthesis of chlorinated polyhydroxyazaromatic compounds include the use of POCl 3 or PCl 5 Direct substitution of the hydroxyl groups of their corresponding compounds, these experimental conditions have changed little over the past 100 years, usually involving tertiary amines (or amides) as catalysts and the use of excess POCl 3 as a solvent. Due to the ever-increasing environmental requirements, the phosphorus oxychloride in the post-reaction treatment and the phosphorus-containing wastewater...

Examples

Embodiment 1

[0020] Add 1000 mg 2,4-dihydroxypyrimidine (8.9 mmol), 50 mg DMAP and 4 mL SOCl to a 50 mL reaction vial 2 , forming a cloudy solution. Slowly add 5.28g (17.8mmol) SOCl of BTC dropwise 2 (4 mL) solution. Heating in an oil bath, controlling the reaction temperature between 65°C and 70°C, and cooling the reflux reaction with refrigerated liquid. After reacting to the complete reaction of the raw materials, the reaction solution was cooled, evaporated to remove the solvent, added to 10 mL of ice water, neutralized with sodium carbonate solution to pH=8-9, extracted with dichloromethane, and the organic layer was separated. After washing with water and brine, and drying with anhydrous sodium sulfate, the solvent was evaporated (or chromatographic column) to obtain 2,4-dichloropyrimidine with a yield of 95%.

[0021] Examples 2-9 The same method as in Example 1 was used to prepare polychlorinated nitrogen heteroaromatic compounds, and the yields are listed in Table 1.

[0022] ...

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