Method for synthetizing 3,6-dichloropyridazine

Abstract

The invention relates to a method for synthetizing 3,6-dichloropyridazine. The method comprises the following steps: taking 3,6-dihydroxy pyridazine and phosphorus oxychloride as raw materials, and reacting in a proper solvent at 0-80 DEG C; and purifying to obtain the pure product 3,6-dichloropyridazine. The method disclosed by the invention has the advantages of easiness for reaction material obtaining, reasonability for price, moderation in reaction condition, easiness for operation, easiness for control, simple post-processing, stability in product quality and high purity.

Description

(1) Technical field

[0001] The invention relates to a pyridazine derivative, in particular to a synthesis method of 3,6-dichloropyridazine. (2) Background technology

[0002] 3,6-Dichloropyridazine is an important raw material for the synthesis of many pesticides and medicines. In the Guangzhou Chemical Industry Journal, Volume 40, Issue 9, published in May 2012, Xin Lei et al. published an article: 3-amino-6-chloro The preparation method of 3,6-dichloropyridazine is disclosed in the microwave synthesis research of pyridazine, and the method comprises the following steps:

[0003] (1) Synthesis of maleic hydrazide:

[0004] Add 72.5 mL hydrazine hydrate (80%) (1.3 mol) into a 500 mL three-neck flask,

[0005] Add 120 mL of 30% hydrochloric acid dropwise, add 98 g of maleic anhydride (1 mol), return to 110 °C

[0006] Stream for 3 h. Cooling and crystallization, suction filtration to obtain a yellow-white solid, washing the filter cake with cold ethanol for 3-4

[0007] ...

Examples

Embodiment 1

[0025] Add 3,6-dihydroxypyridazine (4.48g, 40mmol), phosphorus oxychloride (9.20g, 60mmol) and 20ml of chloroform into a 100mL single-necked round bottom flask. The mixture in the reaction flask was stirred and reacted at 50°C for 4 hours. TLC and GC confirmed the completion of the reaction. After the reaction, the solvent was removed by rotary evaporation to obtain the crude product, which was separated by silica gel column chromatography to obtain the pure product 3,6-dichloropyridazine. After drying, the calculated yield was 72.35%, the purity was 99.03% (GC), and the melting point was 68.1°C -68.7°C (literature 68°C-69°C). Nuclear Magnetic Resonance Analysis: 1H NMR (Deuterated Chloroform): 7.514 ppm(s, 1H).

Embodiment 2

[0027] Add 3,6-dihydroxypyridazine (4.48g, 40mmol), phosphorus oxychloride (9.20g, 60mmol), and DMF 20ml into a 100mL single-necked round bottom flask. The mixture in the reaction flask was stirred and reacted at 50°C for 4 hours. TLC and GC confirmed the completion of the reaction. After the reaction, the solvent was removed by rotary evaporation to obtain the crude product, which was separated by silica gel column chromatography to obtain the pure product 3,6-dichloropyridazine. After drying, the calculated yield was 68.41%, the purity was 98.57% (GC), and the melting point was 68.1°C -68.7°C (literature 68°C-69°C).

Embodiment 3

[0029] Add 3,6-dihydroxypyridazine (11.20 g, 100 mmol), phosphorus oxychloride (46.00 g, 300 mmol), and 150 ml of chloroform into a 500 mL single-necked round bottom flask. The mixture in the reaction flask was stirred and reacted at 65°C for 3.5 hours. TLC and GC confirmed the completion of the reaction. After the reaction, the solvent was removed by rotary evaporation to obtain a crude product, which was separated by silica gel column chromatography to obtain the pure product 3,6-dichloropyridazine. After drying, the calculated yield was 86%.

(1) Technical field

[0001] The invention relates to a pyridazine derivative, in particular to a synthesis method of 3,6-dichloropyridazine. (2) Background technology

[0002] 3,6-Dichloropyridazine is an important raw material for the synthesis of many pesticides and medicines. In the Guangzhou Chemical Industry Journal, Volume 40, Issue 9, published in May 2012, Xin Lei et al. published an article: 3-amino-6-chloro The preparation method of 3,6-dichloropyridazine is disclosed in the microwave synthesis research of pyridazine, and the method comprises the following steps:

[0003] (1) Synthesis of maleic hydrazide:

[0004] Add 72.5 mL hydrazine hydrate (80%) (1.3 mol) into a 500 mL three-neck flask,

[0005] Add 120 mL of 30% hydrochloric acid dropwise, add 98 g of maleic anhydride (1 mol), return to 110 °C

[0006] Stream for 3 h. Cooling and crystallization, suction filtration to obtain a yellow-white solid, washing the filter cake with cold ethanol for 3-4

[0007] ...

Examples

Embodiment 1

[0025] Add 3,6-dihydroxypyridazine (4.48g, 40mmol), phosphorus oxychloride (9.20g, 60mmol) and 20ml of chloroform into a 100mL single-necked round bottom flask. The mixture in the reaction flask was stirred and reacted at 50°C for 4 hours. TLC and GC confirmed the completion of the reaction. After the reaction, the solvent was removed by rotary evaporation to obtain the crude product, which was separated by silica gel column chromatography to obtain the pure product 3,6-dichloropyridazine. After drying, the calculated yield was 72.35%, the purity was 99.03% (GC), and the melting point was 68.1°C -68.7°C (literature 68°C-69°C). Nuclear Magnetic Resonance Analysis: 1H NMR (Deuterated Chloroform): 7.514 ppm(s, 1H).

Embodiment 2

[0027] Add 3,6-dihydroxypyridazine (4.48g, 40mmol), phosphorus oxychloride (9.20g, 60mmol), and DMF 20ml into a 100mL single-necked round bottom flask. The mixture in the reaction flask was stirred and reacted at 50°C for 4 hours. TLC and GC confirmed the completion of the reaction. After the reaction, the solvent was removed by rotary evaporation to obtain the crude product, which was separated by silica gel column chromatography to obtain the pure product 3,6-dichloropyridazine. After drying, the calculated yield was 68.41%, the purity was 98.57% (GC), and the melting point was 68.1°C -68.7°C (literature 68°C-69°C).

Embodiment 3

[0029] Add 3,6-dihydroxypyridazine (11.20 g, 100 mmol), phosphorus oxychloride (46.00 g, 300 mmol), and 150 ml of chloroform into a 500 mL single-necked round bottom flask. The mixture in the reaction flask was stirred and reacted at 65°C for 3.5 hours. TLC and GC confirmed the completion of the reaction. After the reaction, the solvent was removed by rotary evaporation to obtain a crude product, which was separated by silica gel column chromatography to obtain the pure product 3,6-dichloropyridazine. After drying, the calculated yield was 86%.