Improved and efficient process for the synthesis of 2-[2-(1-chlorocyclopropyl)-3-(2-chlorophenyl)-2- hydroxypropyl]-2,4-dihydro-3h-1,2,4-triazole-3-thione (prothioconazole) and its intermediates

A suitable compound technique, applied in the synthesis of 2-[2-(1-chlorocyclopropyl)-3-(2-chlorophenyl)-2-hydroxypropyl]-2,4-dihydro -The improved and effective field of 3H-1,2,4-triazole-3-thione (prothioconazole) and its intermediates can solve the problems that the amplification cannot be effectively saved, it is not easy to scale, etc., and it is easy to repeat , high yield effect

Pending Publication Date: 2020-08-11
GSP CROP SCI PVT
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The method is neither easy to scale up nor cost effective on an industrial scale

Method used

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  • Improved and efficient process for the synthesis of 2-[2-(1-chlorocyclopropyl)-3-(2-chlorophenyl)-2- hydroxypropyl]-2,4-dihydro-3h-1,2,4-triazole-3-thione (prothioconazole) and its intermediates
  • Improved and efficient process for the synthesis of 2-[2-(1-chlorocyclopropyl)-3-(2-chlorophenyl)-2- hydroxypropyl]-2,4-dihydro-3h-1,2,4-triazole-3-thione (prothioconazole) and its intermediates
  • Improved and efficient process for the synthesis of 2-[2-(1-chlorocyclopropyl)-3-(2-chlorophenyl)-2- hydroxypropyl]-2,4-dihydro-3h-1,2,4-triazole-3-thione (prothioconazole) and its intermediates

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0073] Step 1: Preparation of compound shown in formula (III):

[0074] To a mixture of compound represented by formula (IV) (125g, 0.44mol) in methanol (1250ml, 10T / v) was added hydrazine hydrate (224g, 125ml, 4.47mol) at 20-30°C. The reaction mixture was stirred at 75-80°C for 4-5 hours. The progress of the reaction was monitored by HPLC. After the reaction was complete, the reaction mixture was cooled to 20-30°C. The reaction mixture was slowly poured into water (1250ml, 10T / v) at 20-30°C. The resulting suspension was stirred at 20-30°C for 1-2 hours. The product was filtered, washed with methanol (125 ml, 1 T / v), and vacuum dried at 20-30° C. for 20-35 minutes. The solid was dissolved in ethyl acetate (1250ml, 10T / v). Sodium sulfate (125 g, 1 T / w) was added to ethyl acetate. The inorganics were filtered off and washed with ethyl acetate (125ml, 1T / v). Hydrogen chloride gas was bubbled at 20-30°C for 1-1.5 hours. The resulting precipitate was stirred at 20-30°C fo...

Embodiment 2

[0080] Embodiment 2: use oxidant hydrogen peroxide to prepare the compound shown in formula (I):

[0081] Add acetic acid or formic acid to a solution of the compound represented by formula (II) (0.5 g, 0.00145 mol) in dichloromethane (5 ml, 10 T / v) at 20-30°C. The reaction mass was cooled to 0-5°C and hydrogen peroxide (0.146 g, 0.0043 mol) was added at 0-5°C. The reaction mass was stirred at 0-5°C for 2-4 hours and continued at 20-30°C for 12-15 hours. The progress of the reaction was monitored by HPLC analysis. After the reaction was complete, the reaction mass was washed with 10% aqueous sodium bicarbonate solution (10ml, 20T / v), then washed with water (10ml, 20T / v) and brine (10ml, 20T / v). The organic phase was dried over sodium sulfate, filtered and concentrated under reduced pressure. 0.35 g of the compound represented by formula (I) was obtained, which contained 65% of the compound represented by formula (I) according to HPLC analysis.

Embodiment 3

[0082] Embodiment 3: use oxidant sodium nitrite to prepare the compound shown in formula (I):

[0083] To a methanol solution of the compound represented by formula (II) (0.83 g, 0.0023 mol) was added concentrated hydrochloric acid (0.71 g, 0.0069 mol) at 0-5°C. A solution of sodium nitrite (0.158 g, 0.0023 mol) in water (2 ml, 2.4 T / v) was added dropwise at 0-5°C. The reaction was continued at 0-5°C for 1-2 hours. The progress of the reaction was monitored by HPLC analysis. After the reaction is completed, the methanol in the reaction material is distilled off under reduced pressure at 30-40°C. The residue was dissolved in ethyl acetate (15ml, 18T / v) and washed with 10% sodium bicarbonate solution (15ml, 18T / v), water (15ml, 18T / v) and brine solution (15ml, 18T / v) washing. The organic phase was dried over sodium sulfate, filtered and concentrated under reduced pressure. 0.75 g of the compound represented by formula (I) was obtained, which contained 78% of the compound ...

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Abstract

The present invention relates to an improved and efficient process for the synthesis of 2-[2-(1-chlorocyclopropyl)-3-(2-chlorophenyl)-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4- triazole-3-thione, compoundof formula (I) (Prothioconazole). The present invention more particularly relates to an improved process for manufacturing of 2-(1-chloro-cycloprop-1-yl)-3-(2-chloro phenyl)-2-hydroxy propyl-1-hydrazine (compound of formula III) and 2-[2-(1-chlorocyclopropyl)-3-(2-chlorophenyl)-2-hydroxypropyl]-1,2,4-triazolidine-3-thione (compound of formula II) which are mainly used for synthesis of Prothioconazole which is knows as an active compound with microbicidal fungicidal properties.

Description

technical field [0001] The present invention relates to a method for synthesizing 2-[2-(1-chlorocyclopropyl)-3-(2-chlorophenyl)-2-hydroxypropyl]-2,4-dihydro-3H-1, Improved and efficient process for 2,4-triazole-3-thiones (prothioconazole). The present invention more particularly relates to a method for the preparation of intermediates, namely 2-(1-chloro-cycloprop-1-yl)-3-(2-chlorophenyl)-2-hydroxypropyl-1-hydrazine and 2 - an improved method of [2-(1-chlorocyclopropyl)-3-(2-chlorophenyl)-2-hydroxypropyl]-1,2,4-triazolidine-3-thione, the Intermediate used in the synthesis of prothioconazole, an active ingredient with fungicidal properties. Background technique [0002] Prothioconazole, 2-[(2RS)-2-(1-chlorocyclopropyl)-3-(2-chlorophenyl)-2-hydroxypropyl]-2H-1,2,4-triazole -3(4H)-thione, whose structure is shown below, is used as a fungicide to treat infected crops. The molecule itself was first described in US Patent No. 5,789,430. Its structure is reproduced as follows:...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D231/12C07D249/12
CPCC07D249/12B01J31/0215
Inventor S·R·卡达姆N·贾尼R·辛德K·V·沙B·V·沙A·S·古杰拉尔G·拜瑞高德G·西瓦亚J·D·帕瓦尔H·N·帕蒂
Owner GSP CROP SCI PVT
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