A kind of preparation method of substituted phenoxybenzylamine compound and pyrazole carboxamide compound

Abstract

The invention discloses a preparation method of a substituted phenoxybenzylamine compound, which uses p-halobenzonitrile as a starting material, uses R'OH as a solvent in the presence of R'OM, and undergoes hydrogen reduction to obtain substituted The phenoxybenzylamine compound has the advantages of high yield and high purity; the invention also discloses a preparation method of pyrazole carboxamide, by first salting the substituted phenoxybenzylamine compound and then substituting Pyrazole carboxamides were reacted in unexpectedly high yields. The technical scheme of the invention has the advantages of high product purity, high yield, low solvent loss and low production cost.

Description

technical field

[0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a preparation method of substituted phenoxybenzylamine compounds and pyrazole carboxamide compounds. Background technique

[0002] Tolfenpyrad (ISO common name tolfenpyrad) is a pyrazole amide insecticide and acaricide developed by the former Mitsubishi Chemical Corporation of Japan. It belongs to the electron transport inhibitor of the respiratory chain acting on site I. Fungicides do not transfer in plants. They have the characteristics of high efficiency, wide insecticidal spectrum, wide application range, and quick effects. They are widely used in fruit trees, tea, cotton, etc. and high-end ornamental plants. Aphids, flea beetles and other Lepidoptera, Hemiptera, and Thysanoptera pests have special effects. It is reported that it is also effective against fungal powdery mildew such as downy mildew and powdery mildew. Due to its excellent performance on h...

Examples

Embodiment 1

[0047] The preparation method of phenoxybenzylamine compound, reaction formula is as follows:

[0048]

[0049] Include the following steps:

[0050] Add 43.2kg of sodium methoxide solution (mass concentration: 25%, solvent is methanol) and 25.9kg of p-cresol to the 500L reaction kettle in sequence, stir for 30 minutes, and reflux for 1 hour; after the heat preservation, remove the methanol; Finally, 150kg of DMF was added, stirred for 30min, and 32.9kg of p-chlorobenzonitrile was added; the temperature was raised to 155°C, kept for 2h, and samples were taken for detection, and the reaction was qualified. The above solution was precipitated under negative pressure, the solvent was removed, 110.5kg of water was added, the temperature was lowered to precipitate crystals, suction filtration, rinsing, and drying to obtain about 49.7kg of 4-(4'-methylphenoxy)benzonitrile, Normalization 99%, yield 98.2%, melting point: 71-73°C, see mass spectrum figure 1 .

[0051] Into the 50...

Embodiment 2

[0053]Add 219.3kg potassium tert-butoxide solution (mass concentration: 12%, solvent is tert-butanol) and 25.9kg p-cresol to the 500L reactor successively, stir for 30 minutes, and keep it under reflux for 1 hour; Butanol; after the precipitation is completed, add 150kg of DMF, stir for 30min, add 32.9kg of p-chlorobenzonitrile; raise the temperature to 145°C, keep it warm for 2h, take a sample for detection, and the reaction is qualified. The above solution was precipitated under negative pressure, the solvent was removed, 110.5kg of water was added, the temperature was lowered to precipitate crystals, suction filtration, rinsing, and drying to obtain about 48.9kg of 4-(4'-methylphenoxy)benzonitrile, Normalization 98%, yield 95.6%, melting point: 71-73°C.

Embodiment 3

[0055] Add 150kg of toluene, 13.9kg of potassium hydroxide, and 25.9kg of p-cresol to the 500L reactor in sequence, and keep it under reflux for 12 hours; after the heat preservation is over, remove the toluene; Benzonitrile; heat up to 145°C, keep warm for 2 hours, take a sample for testing, and the reaction is qualified. The above solution was precipitated under negative pressure, the solvent was removed, 110.5kg of water was added, the temperature was lowered to precipitate crystals, suction filtration, rinsing, and drying to obtain about 48.4kg of 4-(4'-methylphenoxy)benzonitrile, Normalization 95%, yield 91.7%, melting point: 71-73°C.

technical field

[0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a preparation method of substituted phenoxybenzylamine compounds and pyrazole carboxamide compounds. Background technique

[0002] Tolfenpyrad (ISO common name tolfenpyrad) is a pyrazole amide insecticide and acaricide developed by the former Mitsubishi Chemical Corporation of Japan. It belongs to the electron transport inhibitor of the respiratory chain acting on site I. Fungicides do not transfer in plants. They have the characteristics of high efficiency, wide insecticidal spectrum, wide application range, and quick effects. They are widely used in fruit trees, tea, cotton, etc. and high-end ornamental plants. Aphids, flea beetles and other Lepidoptera, Hemiptera, and Thysanoptera pests have special effects. It is reported that it is also effective against fungal powdery mildew such as downy mildew and powdery mildew. Due to its excellent performance on h...

Examples

Embodiment 1

[0047] The preparation method of phenoxybenzylamine compound, reaction formula is as follows:

[0048]

[0049] Include the following steps:

[0050] Add 43.2kg of sodium methoxide solution (mass concentration: 25%, solvent is methanol) and 25.9kg of p-cresol to the 500L reaction kettle in sequence, stir for 30 minutes, and reflux for 1 hour; after the heat preservation, remove the methanol; Finally, 150kg of DMF was added, stirred for 30min, and 32.9kg of p-chlorobenzonitrile was added; the temperature was raised to 155°C, kept for 2h, and samples were taken for detection, and the reaction was qualified. The above solution was precipitated under negative pressure, the solvent was removed, 110.5kg of water was added, the temperature was lowered to precipitate crystals, suction filtration, rinsing, and drying to obtain about 49.7kg of 4-(4'-methylphenoxy)benzonitrile, Normalization 99%, yield 98.2%, melting point: 71-73°C, see mass spectrum figure 1 .

[0051] Into the 50...

Embodiment 2

[0053]Add 219.3kg potassium tert-butoxide solution (mass concentration: 12%, solvent is tert-butanol) and 25.9kg p-cresol to the 500L reactor successively, stir for 30 minutes, and keep it under reflux for 1 hour; Butanol; after the precipitation is completed, add 150kg of DMF, stir for 30min, add 32.9kg of p-chlorobenzonitrile; raise the temperature to 145°C, keep it warm for 2h, take a sample for detection, and the reaction is qualified. The above solution was precipitated under negative pressure, the solvent was removed, 110.5kg of water was added, the temperature was lowered to precipitate crystals, suction filtration, rinsing, and drying to obtain about 48.9kg of 4-(4'-methylphenoxy)benzonitrile, Normalization 98%, yield 95.6%, melting point: 71-73°C.

Embodiment 3

[0055] Add 150kg of toluene, 13.9kg of potassium hydroxide, and 25.9kg of p-cresol to the 500L reactor in sequence, and keep it under reflux for 12 hours; after the heat preservation is over, remove the toluene; Benzonitrile; heat up to 145°C, keep warm for 2 hours, take a sample for testing, and the reaction is qualified. The above solution was precipitated under negative pressure, the solvent was removed, 110.5kg of water was added, the temperature was lowered to precipitate crystals, suction filtration, rinsing, and drying to obtain about 48.4kg of 4-(4'-methylphenoxy)benzonitrile, Normalization 95%, yield 91.7%, melting point: 71-73°C.

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