CN102286005B - Method for synthesizing fluthiacet-ethyl - Google Patents

Abstract

The invention provides a method for synthesizing fluthiacet-ethyl (also known as oxazine methyl oxalate), which is to perform condensation reaction on 2-chloro-4-fluoro-5-aminobenzenethioacetate and tetrahydro- [1, 3, 4] thiadiazolo [3, 4-alpha ] pyridazine-1, 3-diketone under the catalysis of acid to obtain fluthiacet-ethyl.

Description

A kind of method for synthesizing fluthiazol

technical field

The invention belongs to the synthesis of organic compounds in the field of chemistry. It specifically relates to a preparation method of fluthiacet-methyl.

technical background

The structure of the herbicide fluthiazate (also known as fenoxetate methyl) is as follows:

This herbicide has the characteristics of ultra-high efficiency, broad-spectrum, and safety. Its activity is equivalent to or higher than that of sulfonylurea herbicides widely used at present. Soybean and corn are extremely safe, and there is no adverse effect on stubble crops under excessive dosage (120g a.i./ha). Fluthiacet-ethyl is particularly effective against some difficult-to-control broad-leaved weeds, has low toxicity to mammals, and is safe for the environment. It has been put into production at present.

Fluthiacet-ethyl is an imide herbicide developed by Japan Combination Chemicals and Syngenta in recent years. It has the characteristics of ultra-high efficiency, broad spectrum, and safety. It is a new pesticide variety that meets the requirements of green agriculture.

The people such as Yamaguchi first reported in 1988 the synthetic base herbicidal activity of " thiadiazolopyridazine bicyclic " series compound including fluthiacet, and applied for a patent (Yamaguchi M, Watase Y, Kambe T, Katou S. EP273417, 1988; Yamaguchi M, Watase Y, Kambe T, Katou S. JP63264489, 1988; Yamaguchi M, Watase Y, Kambe T, Katou S. US4906279, 1988). Its synthetic route is as follows. This route has relatively short steps, but uses highly toxic substances such as thiophosgene and phosgene as raw materials, and hexahydropyridazine is relatively difficult to synthesize, and even the purchase price is very expensive.

In order to avoid using thiophosgene and phosgene, it has been reported to replace thiophosgene with carbon disulfide, replace phosgene with triphosgene, and replace hexahydropyridazine with hexahydropyridazine hydrochloride at the same time, but hexahydropyridazine hydrochloride is still very Difficult to synthesize (clean production process of ultra-efficient herbicide fluthiazol, Acta Chemical Society, 2004, 55(12), 2072-2075). Since then, many patents and papers have reported similar synthetic methods of similar compounds (Pissiotas G, Moser H, Brunner H G.EP611768.1994; Ota C, Natsume B.EP698604.1996; Yamaguchi M, Suzuki C, Miyazawa T, Matsunari K, Nakamura Y. EP312064.1989; Liu Changlin, Wang Zhaodong. Super Effective Herbicide Fluthiacet-methyl. Fine and Specialty Chemicals (Fine and Specialty Chemicals), 2002 (2): 19-20. Among them, EP312064 synthesizes fluorine with a new route Thiacetate, its synthetic route is as follows:

This route is still a tandem synthesis route. Although hexahydropyridazine is not used, the steps are relatively long, and highly toxic raw materials such as thiophosgene and phosgene are still used in steps I and III respectively.

For this reason, the present inventor has researched and developed a new method for synthesizing [1,3,4]thiadiazolo[3,4-α]pyridazine-1,3-dione (Zhu Hongjun, Xi Binbin, Lang Yucheng, etc. A method for synthesizing tetrahydro-[1,3,4]thiadiazolo[3,4-α]pyridazine-1,3-dione, CN201110091918.8, 2011-4-13), the intermediate The body can directly condense with 2-chloro-4-fluoro-5-aminophenylthioacetic acid methyl ester to obtain fluthiacet-methyl, so that the original serial synthesis route can be changed into a parallel synthesis route, which can increase the yield by 50%. above. Simultaneously because the raw material 1 that this method adopts, 3,4] thiadiazolo [3,4-alpha] pyridazine-1, the advantages such as 3-dione synthesis has easy and simple operation, safety, the present invention has obvious economic benefit and social benefits.

Contents of the invention

Purpose of the present invention: provide a kind of method of synthesizing fluthiatil

The present invention uses 2-chloro-4-fluoro-5-aminophenylthioacetic acid methyl ester and tetrahydro-[1,3,4]thiadiazolo[3,4-α]pyridazine-1,3-di Ketones are reacted with bases to obtain fluthiacet-ethyl.

Its synthetic route is as follows:

Specifically, methyl 2-chloro-4-fluoro-5-aminophenylthioacetate and tetrahydro-[1,3,4]thiadiazolo[3,4-α]pyridazine-1,3-di Ketone is the raw material, its molar ratio is 1:1.1-1.1:1, and one of methanol, ethanol, n-propanol, isopropanol, n-butanol, sec-butanol and tert-butanol is used as the solvent, selected from One of formic acid, acetic acid, propionic acid, HCl and H ₂ SO ₄ is used as a catalyst, and the reflux reaction is used to obtain fluthiacet-methyl.

Detailed ways

The present invention will be described in detail below through specific examples.

Embodiment 1: the synthesis of fluthiatil

Add 50mL of anhydrous methanol, 0.1mL of glacial acetic acid and tetrahydro-[1,3,4]thiadiazolo[3,4-α]pyridazine-1,3-dione (0.86g, 5mmol) was heated to reflux, and methyl 2-chloro-4-fluoro-5-aminophenylthioacetate (1.25g, 5mmol) was added in batches, the addition was completed in 30min, and the reflux was continued for 4h. The solvent was removed by rotary evaporation to obtain a white solid, which was recrystallized from ethanol to obtain 1.43 g of fluthiatil, with a yield of 71.1% and a melting point of 105-106°C.

Embodiment 2: the synthesis of fluthiatil

Add 50mL of anhydrous methanol, 0.1mL of glacial acetic acid and methyl 2-chloro-4-fluoro-5-aminophenylthioacetate (1.25g, 5mmol) into a 100mL four-neck flask and heat to reflux, then add tetrahydro-[ 1,3,4]Thiadiazolo[3,4-α]pyridazine-1,3-dione (0.86g, 5mmol) was added after 30min, and the reflux continued for 4h. The solvent was removed by rotary evaporation to obtain a white solid, which was recrystallized from ethanol to obtain 0.65 g of fluthiatil, with a yield of 32.3% and a melting point of 105-106°C.

Embodiment 3: the synthesis of fluthiatil

In a 100mL four-neck flask, add tetrahydro-[1,3,4]thiadiazolo[3,4-α]pyridazine-1,3-dione (0.86g, 5mmol), 2-chloro-4-fluoro - Methyl 5-aminophenylthioacetate (1.25g, 5mmol), 50mL of anhydrous methanol and 0.1mL of glacial acetic acid, stirred until the solid dissolved, then heated to reflux for 4h. The solvent was removed by rotary evaporation to obtain a white solid, which was recrystallized from ethanol to obtain 0.80 g of fluthiatil, with a yield of 39.7% and a melting point of 105-106°C.

Embodiment 4: the synthesis of fluthiatil

Add 50mL of anhydrous methanol, 0.1mL of glacial acetic acid and tetrahydro-[1,3,4]thiadiazolo[3,4-α]pyridazine-1,3-dione (0.86g, 5mmol) was heated to reflux, and methyl 2-chloro-4-fluoro-5-aminophenylthioacetate (1.37g, 5.5mmol) was added in batches, the addition was completed in 30min, and the reflux was continued for 4h. The solvent was removed by rotary evaporation to obtain a white solid, which was recrystallized from ethanol to obtain 1.39 g of fluthiatil, with a yield of 68.9% and a melting point of 105-106°C.

Embodiment 5: the synthesis of fluthiatil

Add 50mL of anhydrous methanol, 0.1mL of glacial acetic acid and tetrahydro-[1,3,4]thiadiazolo[3,4-α]pyridazine-1,3-dione (0.95g, 5.5mmol) was heated to reflux, and methyl 2-chloro-4-fluoro-5-aminophenylthioacetate (1.25g, 5mmol) was added in batches, the addition was completed in 30min, and the reflux was continued for 4h. The solvent was removed by rotary evaporation to obtain a white solid, which was recrystallized from ethanol to obtain 1.45 g of fluthiatil, with a yield of 71.8% and a melting point of 105-106°C.

Embodiment 6: the synthesis of fluthiatil

Add 50mL absolute ethanol, 0.1mL glacial acetic acid and tetrahydro-[1,3,4]thiadiazolo[3,4-α]pyridazine-1,3-dione (0.86g, 5mmol) was heated to reflux, and methyl 2-chloro-4-fluoro-5-aminophenylthioacetate (1.25g, 5mmol) was added in batches, the addition was completed in 30min, and the reflux was continued for 3.5h. The solvent was removed by rotary evaporation to obtain a white solid, which was recrystallized from ethanol to obtain 1.31 g of diacetate with a yield of 65.0% and a melting point of 105-106°C.

Embodiment 7: the synthesis of fluthiatil

Add 50mL of anhydrous isopropanol, 0.1mL of glacial acetic acid and tetrahydro-[1,3,4]thiadiazolo[3,4-α]pyridazine-1,3-dione (0.86 g, 5mmol) was heated to reflux, and methyl 2-chloro-4-fluoro-5-aminophenylthioacetate (1.25g, 5mmol) was added in batches, and the addition was completed in 30min, and the reflux was continued for 3.5h. The solvent was removed by rotary evaporation to obtain a white solid, which was recrystallized from ethanol to obtain 1.30 g of diacetate with a yield of 64.5% and a melting point of 105-106°C.

Embodiment 8: the synthesis of fluthiatil

Add 50mL of anhydrous n-propanol, 0.1mL of glacial acetic acid and tetrahydro-[1,3,4]thiadiazolo[3,4-α]pyridazine-1,3-dione (0.86 g, 5mmol) was heated to reflux, and methyl 2-chloro-4-fluoro-5-aminophenylthioacetate (1.25g, 5mmol) was added in portions, and the addition was completed in 30min, and the reflux was continued for 2h. The solvent was removed by rotary evaporation to obtain a white solid, which was recrystallized from ethanol to obtain diacetate 1.14 with a yield of 56.6% and a melting point of 105-106°C.

Embodiment 9: the synthesis of fluthiazate

Add 50mL of anhydrous tert-butanol, 0.1mL of glacial acetic acid and tetrahydro-[1,3,4]thiadiazolo[3,4-α]pyridazine-1,3-dione (0.86 g, 5mmol) was heated to reflux, and methyl 2-chloro-4-fluoro-5-aminophenylthioacetate (1.25g, 5mmol) was added in batches, and the addition was completed in 30min, and the reflux was continued for 3.5h. The solvent was removed by rotary evaporation to obtain a white solid, which was recrystallized from ethanol to obtain 1.35 g of diacetate with a yield of 67.0% and a melting point of 105-106°C.

Embodiment 10: the synthesis of fluthiatil

Add 50mL of anhydrous sec-butanol, 0.1mL of glacial acetic acid and tetrahydro-[1,3,4]thiadiazolo[3,4-α]pyridazine-1,3-dione (0.86 g, 5mmol) was heated to reflux, and methyl 2-chloro-4-fluoro-5-aminophenylthioacetate (1.25g, 5mmol) was added in portions, and the addition was completed after 30min, and the reflux was continued for 1.8h. The solvent was removed by rotary evaporation to obtain a white solid, which was recrystallized from ethanol to obtain 0.91 g of diacetate with a yield of 45.2% and a melting point of 105-106°C.

Embodiment 11: the synthesis of fluthiazate

Add 50mL of anhydrous n-butanol, 0.1mL of glacial acetic acid and tetrahydro-[1,3,4]thiadiazolo[3,4-α]pyridazine-1,3-dione (0.86 g, 5 mmol) was heated to reflux, and methyl 2-chloro-4-fluoro-5-aminophenylthioacetate (1.25 g, 5 mmol) was added in batches, and the addition was completed in 30 minutes, and the reflux was continued for 50 minutes. The solvent was removed by rotary evaporation to obtain a white solid, which was recrystallized from ethanol to obtain 0.63 g of diacetate with a yield of 31.3% and a melting point of 105-106°C.

Embodiment 12: the synthesis of fluthiazate

Add 50mL of anhydrous methanol, 0.1mL formic acid and tetrahydro-[1,3,4]thiadiazolo[3,4-α]pyridazine-1,3-dione (0.86g, 5mmol ) was heated to reflux, and methyl 2-chloro-4-fluoro-5-aminophenylthioacetate (1.25 g, 5 mmol) was added in batches, and the addition was completed in 30 minutes, and the reflux was continued for 4 hours. The solvent was removed by rotary evaporation to obtain a white solid, which was recrystallized from ethanol to obtain 1.42 g of fluthiatil, with a yield of 70.5% and a melting point of 105-106°C.

Embodiment 13: the synthesis of fluthiazate

Add 50mL of anhydrous methanol, 0.1mL propionic acid and tetrahydro-[1,3,4]thiadiazolo[3,4-α]pyridazin-1,3-one (0.86g, 5mmol ) was heated to reflux, and methyl 2-chloro-4-fluoro-5-aminophenylthioacetate (1.25 g, 5 mmol) was added in batches, and the addition was completed in 30 minutes, and the reflux was continued for 4 hours. The solvent was removed by rotary evaporation to obtain a white solid, which was recrystallized from ethanol to obtain 1.44 g of fluthiatil, with a yield of 71.5% and a melting point of 105-106°C.

Embodiment 14: Synthesis of fluthiazate

Add 50mL of anhydrous methanol, 0.1mL of concentrated sulfuric acid and tetrahydro-[1,3,4]thiadiazolo[3,4-α]pyridazine-1,3-dione (0.86g, 5mmol) was heated to reflux, and methyl 2-chloro-4-fluoro-5-aminophenylthioacetate (1.25g, 5mmol) was added in batches, the addition was completed in 30min, and the reflux was continued for 4h. The solvent was removed by rotary evaporation to obtain a white solid, which was recrystallized from ethanol to obtain 1.28 g of fluthiatil, with a yield of 63.5% and a melting point of 105-106°C.

Claims (1)

1. A method for synthesizing fluthiazol, characterized in that: 2-chloro-4-fluoro-5-aminophenylthioacetic acid methyl ester and tetrahydro-[1,3,4]thiadiazolo [3,4-α]pyridazine-1,3-dione as raw material, its molar ratio is 1:1.1-1.1:1, to be selected from methanol, ethanol, n-propanol, isopropanol, n-butanol, One of sec-butanol and tert-butanol is used as _a solvent, one selected from formic acid, acetic acid, propionic acid, HCl and _H2SO4 is used as a catalyst, and the reflux reaction is used to obtain fluthiatil.