Synthesis method of Fenpropidin

Abstract

The invention discloses a synthesis method of Fenpropidin. The synthesis method comprises the steps of: chloridizing tertiary butyl-beta-methyl phenylpropanol by utilizing a hydrogenation product of 4-tert-butyl phenyl isobutyraldehyde through sulfoxide chloride in the presence of a catalyst DMF (Dimethyl Formamide), and reacting with piperidine to obtain a target product, namely Fenpropidin. The synthesis method is simple in process and high in reaction yield and product content, is free of environmental pollution and has the advantages of simplicity in operation, simple device, less three wastes, low cost and the like.

Description

technical field

[0001] The invention relates to a synthetic method of fenpropidin. Background technique

[0002] Fenpropidin: 1-(3-(4-tert-butylphenyl)-2-methylpropyl)piperidine is a systemic fungicide and a sterol decomposition inhibitor. It is particularly effective against powdery mildew, especially powdery mildew, rye sporophyte and puccinia, and the spraying rate of cereal crops is 750g / ha. For example, 500-700g (a.i.) / ha can prevent and control barley powdery mildew and rust, and has therapeutic effect, and the duration of effect is about 28 days.

[0003] Fenpropidin is a yellow liquid with a relative density of 0.91; a refractive index of 1.5062; a boiling point of 100°C (0.53Pa). Solubility (25°C): water 350mg / kg (pH 7), acetone, chloroform, dioxane, ethanol, ethyl acetate, heptane, xylene>250g / L. It is stable for more than 3 years in a closed container at room temperature, and its aqueous solution is stable to ultraviolet light. Rat acute oral LD501800mg / kg....

Examples

Embodiment 1

[0018] Add 103g of p-tert-butyl-β-methylphenylpropanol to a 500ml round-bottomed flask, then add 0.5g of DMF, heat up to 40°C, add 62.5g of thionyl chloride dropwise, after the dropwise addition, keep warm at 90°C for 1 Hour. HCl, SO produced during the reaction process 2 The gas is absorbed in stages with water and 30% NaOH aqueous solution. After the heat preservation is finished, neutralize with liquid caustic soda to PH=8, and let stand to separate into layers. The upper layer is the reacted intermediate p-tert-butyl-β-methylphenylchloropropane. 113g of the intermediate was obtained by weighing, the analytical content (GC normalization method) was 98.2%, and the yield was 99.4%.

[0019] Put the p-tert-butyl-β-methylphenylchloropropane, the product of the first halogenation synthesis, into a 500ml four-neck flask, add 127.5g of piperidine, raise the temperature to 110°C, and keep it under reflux for 8 hours. After the sampling is qualified, use then Neutralize to PH = ...

Embodiment 2

[0021] Add 206g of p-tert-butyl-β-methylphenylpropanol to a 1000ml round bottom flask, then add 1g of DMF, raise the temperature to 40°C, add 125g of thionyl chloride dropwise, and keep the temperature at 90°C for 1 hour after the dropwise addition. HCl, SO produced during the reaction process 2 The gas is absorbed in stages with water and 30% NaOH aqueous solution. After the heat preservation is finished, neutralize with liquid caustic soda to PH=8, and let stand to separate into layers. The upper layer is the reacted intermediate p-tert-butyl-β-methylphenylchloropropane. Weighed 225g of the intermediate, the analytical content (GC normalization method) was 98%, and the yield was 99.2%.

[0022] Put p-tert-butyl-β-methylphenylchloropropane, the product of the first halogenation synthesis, into a 1000ml four-neck flask, add 255g of piperidine, heat up to 110°C, and keep at reflux for 8 hours. After the sampling is qualified, use 30% NaOH aqueous solution was neutralized to ...

Embodiment 3

[0024] Add 309g of p-tert-butyl-β-methylphenylpropanol to a 1000ml round bottom flask, then add 1.5g of DMF, raise the temperature to 40°C, add 187.5g of thionyl chloride dropwise, after the dropwise addition, keep warm at 90°C for 1 Hour. HCl, SO produced during the reaction process 2 The gas is absorbed in stages with water and 30% NaOH aqueous solution. After the heat preservation is finished, neutralize with liquid caustic soda to PH=8, and let stand to separate into layers. The upper layer is the reacted intermediate p-tert-butyl-β-methylphenylchloropropane. Weighed 336.5g of the intermediate, the analytical content (GC normalization method) was 98.2%, and the yield was 98.7%.

[0025] Put the p-tert-butyl-β-methylphenylchloropropane, the product of the first halogenation synthesis, into a 2000ml four-necked flask, add 382.5g of piperidine, raise the temperature to 110°C, and keep it under reflux for 8 hours. After the sampling is qualified, use then Neutralize to PH ...

technical field

[0001] The invention relates to a synthetic method of fenpropidin. Background technique

[0002] Fenpropidin: 1-(3-(4-tert-butylphenyl)-2-methylpropyl)piperidine is a systemic fungicide and a sterol decomposition inhibitor. It is particularly effective against powdery mildew, especially powdery mildew, rye sporophyte and puccinia, and the spraying rate of cereal crops is 750g / ha. For example, 500-700g (a.i.) / ha can prevent and control barley powdery mildew and rust, and has therapeutic effect, and the duration of effect is about 28 days.

[0003] Fenpropidin is a yellow liquid with a relative density of 0.91; a refractive index of 1.5062; a boiling point of 100°C (0.53Pa). Solubility (25°C): water 350mg / kg (pH 7), acetone, chloroform, dioxane, ethanol, ethyl acetate, heptane, xylene>250g / L. It is stable for more than 3 years in a closed container at room temperature, and its aqueous solution is stable to ultraviolet light. Rat acute oral LD501800mg / kg....

Examples

Embodiment 1

[0018] Add 103g of p-tert-butyl-β-methylphenylpropanol to a 500ml round-bottomed flask, then add 0.5g of DMF, heat up to 40°C, add 62.5g of thionyl chloride dropwise, after the dropwise addition, keep warm at 90°C for 1 Hour. HCl, SO produced during the reaction process 2 The gas is absorbed in stages with water and 30% NaOH aqueous solution. After the heat preservation is finished, neutralize with liquid caustic soda to PH=8, and let stand to separate into layers. The upper layer is the reacted intermediate p-tert-butyl-β-methylphenylchloropropane. 113g of the intermediate was obtained by weighing, the analytical content (GC normalization method) was 98.2%, and the yield was 99.4%.

[0019] Put the p-tert-butyl-β-methylphenylchloropropane, the product of the first halogenation synthesis, into a 500ml four-neck flask, add 127.5g of piperidine, raise the temperature to 110°C, and keep it under reflux for 8 hours. After the sampling is qualified, use then Neutralize to PH = ...

Embodiment 2

[0021] Add 206g of p-tert-butyl-β-methylphenylpropanol to a 1000ml round bottom flask, then add 1g of DMF, raise the temperature to 40°C, add 125g of thionyl chloride dropwise, and keep the temperature at 90°C for 1 hour after the dropwise addition. HCl, SO produced during the reaction process 2 The gas is absorbed in stages with water and 30% NaOH aqueous solution. After the heat preservation is finished, neutralize with liquid caustic soda to PH=8, and let stand to separate into layers. The upper layer is the reacted intermediate p-tert-butyl-β-methylphenylchloropropane. Weighed 225g of the intermediate, the analytical content (GC normalization method) was 98%, and the yield was 99.2%.

[0022] Put p-tert-butyl-β-methylphenylchloropropane, the product of the first halogenation synthesis, into a 1000ml four-neck flask, add 255g of piperidine, heat up to 110°C, and keep at reflux for 8 hours. After the sampling is qualified, use 30% NaOH aqueous solution was neutralized to ...

Embodiment 3

[0024] Add 309g of p-tert-butyl-β-methylphenylpropanol to a 1000ml round bottom flask, then add 1.5g of DMF, raise the temperature to 40°C, add 187.5g of thionyl chloride dropwise, after the dropwise addition, keep warm at 90°C for 1 Hour. HCl, SO produced during the reaction process 2 The gas is absorbed in stages with water and 30% NaOH aqueous solution. After the heat preservation is finished, neutralize with liquid caustic soda to PH=8, and let stand to separate into layers. The upper layer is the reacted intermediate p-tert-butyl-β-methylphenylchloropropane. Weighed 336.5g of the intermediate, the analytical content (GC normalization method) was 98.2%, and the yield was 98.7%.

[0025] Put the p-tert-butyl-β-methylphenylchloropropane, the product of the first halogenation synthesis, into a 2000ml four-necked flask, add 382.5g of piperidine, raise the temperature to 110°C, and keep it under reflux for 8 hours. After the sampling is qualified, use then Neutralize to PH ...

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