A kind of synthetic method of spirotetramat

Abstract

The present invention provides a method for synthesizing spirotetramat, and relates to the technical field of pesticide chemical industry. The present invention mixes SN-1 intermediate, ethyl chloroformate, inorganic acid binding agent, amine catalyst and organic solvent, performs condensation reaction, and obtains spirotetramat; The inorganic acid binding agent includes at least one of carbonate, bicarbonate and hydroxide. The present invention uses at least one of carbonate, bicarbonate and hydroxide as inorganic acid binding agent, which has no irritating smell, low cost and can be dissolved in water, and does not produce organic alkali wastewater in the synthesis process of spirotetramat, greatly reducing the cost of organic wastewater treatment, and does not produce nitrogen-containing waste gas in the subsequent purification process, and the synthesis method is environmentally friendly. Moreover, the synthesis method provided by the present invention has high product yield, high purity, light product appearance color, high product quality, short synthesis route, short production cycle, high production efficiency, simple operation, low production cost, and is suitable for industrial production.

Description

Technical Field

[0001] The invention relates to the technical field of pesticide chemical industry, and in particular to a method for synthesizing spirotetramat. Background Art

[0002] Spirotetramat is a new second-generation tetraketanic acid insecticide developed by Bayer. Its chemical name is cis-3-(2,5-dimethylphenyl)-8-methoxy-2-oxo-1-azaspiro[4.5]-dec-3-en-4-ylethyl acetate. It is the only modern insecticide with bidirectional systemic conduction in xylem and phloem so far. It has the characteristics of long-lasting effect, high efficiency and broad spectrum. Spirotetramat is a lipid synthesis inhibitor. Its mechanism of action is to affect the development of mites and whiteflies, inhibit the biosynthesis of their lipid bodies, cause poisoning and death of larvae, and reduce the reproductive capacity of adults. It has no cross-resistance with existing pesticides.

[0003] At present, the traditional synthesis route of spirotetramat mainly uses the raw material cis-3-(2,5-dimethylphenyl)-8-methoxy-2-oxo-1-azaspiro[4,5]-dec-3-en-4-ol (SN-1 intermediate for short), ethyl chloroformate and organic base inorganic acid-binding agent (triethylamine or pyridine) for condensation reaction to prepare it. However, the product yield of the above synthesis method is low, and the above organic base inorganic acid-binding agent has a pungent odor and will dissolve in water, which greatly increases the cost of wastewater treatment. Summary of the invention

[0004] In view of this, the object of the present invention is to provide a method for synthesizing spirotetramat. The synthesis method provided by the present invention has high yield, does not generate organic wastewater, and has little pollution.

[0005] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0006] The present invention provides a method for synthesizing spirotetramat, comprising the following steps:

[0007] The SN-1 intermediate, ethyl chloroformate, an inorganic acid-binding agent, an amine catalyst and an organic solvent are mixed to carry out a condensation reaction to obtain spirotetramat; the inorganic acid-binding agent comprises at least one of a carbonate, a bicarbonate and a hydroxide;

[0008]

[0009] Preferably, the molar ratio of the SN-1 intermediate to ethyl chloroformate is 1:(1-1.5).

[0010] Preferably, the molar ratio of the SN-1 intermediate to the inorganic acid-binding agent is 1:(1-2).

[0011] Preferably, the amine catalyst comprises at least one of tetramethylammonium halide, tetra-n-butylammonium halide, tetraalkylammonium halide, phenyltrialkylammonium halide, benzyltrialkylammonium halide, hexadecylmethylammonium halide, dodecylmethylammonium halide, tetramethylammonium perchlorate, tetramethylammonium p-toluenesulfonate, tetra-n-butylammonium perchlorate and tetra-n-butylammonium hydrogen sulfate.

[0012] Preferably, the tetramethylammonium halide comprises at least one of tetramethylammonium chloride, tetramethylammonium bromide and tetramethylammonium iodide;

[0013] The tetra-n-butylammonium halide comprises at least one of tetra-n-butylammonium chloride, tetra-n-butylammonium bromide and tetra-n-butylammonium iodide;

[0014] The tetraalkylammonium halide includes at least one of tetrapropylammonium bromide, tetra-n-propylammonium iodide, tetra-n-pentylammonium bromide, tetra-n-hexylammonium bromide, tetra-n-heptylammonium bromide, tetra-n-octylammonium bromide and methyltri-n-octylammonium chloride;

[0015] The phenyltrialkylammonium halide includes at least one of phenyltrimethylammonium chloride, phenyltrimethylammonium bromide, phenyltrimethylammonium iodide and phenyltriethylammonium chloride;

[0016] The benzyltrialkylammonium halide includes at least one of benzyltrimethylammonium chloride, benzyltrimethylammonium bromide, benzyltriethylammonium chloride, benzyltriethylammonium bromide and benzyltri-n-butylammonium;

[0017] The hexadecyl methyl ammonium halide includes at least one of hexadecyl dimethyl ammonium chloride, hexadecyl trimethyl ammonium chloride and hexadecyl trimethyl ammonium bromide;

[0018] The dodecyl methyl ammonium halide includes dodecyl trimethyl ammonium chloride and / or dodecyl trimethyl ammonium bromide.

[0019] Preferably, the mass of the amine catalyst is 0.1 to 5% of the mass of the SN-1 intermediate.

[0020] Preferably, the organic solvent includes at least one of a halogenated alkane solvent, a benzene solvent and an ester solvent.

[0021] Preferably, the temperature of the condensation reaction is 0-100°C.

[0022] Preferably, after the condensation reaction, the obtained condensation reaction liquid is further purified, and the purification includes: solid-liquid separation of the obtained condensation reaction liquid, mixing the obtained liquid component with water, adjusting the pH value to 3-4, layering, and sequentially washing the obtained organic phase with water, removing the solvent and recrystallizing.

[0023] Preferably, the recrystallization solvent includes one or more of petroleum ether, n-hexane, n-heptane, toluene, xylene and trimethylbenzene.

[0024] The present invention provides a method for synthesizing spirotetramat, comprising the following steps: mixing an SN-1 intermediate, ethyl chloroformate, an inorganic acid-binding agent, an amine catalyst and an organic solvent, and performing a condensation reaction to obtain spirotetramat; the inorganic acid-binding agent comprises at least one of carbonate, bicarbonate and hydroxide. The traditional method for synthesizing spirotetramat mainly uses an organic base (such as triethylamine, pyridine) as an acid-binding agent to react and synthesize spirotetramat, which has high production cost and generates a large amount of nitrogen-containing waste gas during the recovery of triethylamine. The present invention uses at least one of carbonate, bicarbonate and hydroxide as an inorganic acid-binding agent, which has no irritating odor, low cost and can be dissolved in water, and does not produce organic alkali wastewater in the synthesis process of spirotetramat, greatly reducing the cost of organic wastewater treatment. Moreover, the synthesis method provided by the present invention has high product yield, high purity, light product appearance color, high product quality, short synthesis route, short production cycle, high production efficiency, simple operation, low production cost, and is suitable for industrial production.

[0025] Furthermore, the present invention purifies the condensation reaction liquid, and no nitrogen-containing waste gas is generated during the purification process, so the synthesis method is environmentally friendly. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 The mass spectrum of spirotetramat prepared in Example 2 is shown in FIG. DETAILED DESCRIPTION

[0027] The present invention provides a method for synthesizing spirotetramat, comprising the following steps:

[0028] The SN-1 intermediate, ethyl chloroformate, an inorganic acid-binding agent, an amine catalyst and an organic solvent are mixed to carry out a condensation reaction to obtain spirotetramat; the inorganic acid-binding agent comprises at least one of a carbonate, a bicarbonate and a hydroxide;

[0029]

[0030] In the present invention, unless otherwise specified, all raw material components are commercially available products well known to those skilled in the art.

[0031] In the present invention, the molar ratio of the SN-1 intermediate (cis-3-(2,5-dimethylphenyl)-8-methoxy-2-oxo-1-azaspiro[4,5]-dec-3-en-4-ol) to ethyl chloroformate is preferably 1:(1-1.5), more preferably 1:(1-1.2).

[0032] In the present invention, the inorganic acid-binding agent includes at least one of carbonate, bicarbonate and hydroxide; the carbonate preferably includes sodium carbonate and / or potassium carbonate; the bicarbonate preferably includes sodium bicarbonate and / or potassium bicarbonate; the hydroxide preferably includes at least one of sodium hydroxide, potassium hydroxide and lithium hydroxide. In the present invention, the molar ratio of the SN-1 intermediate to the inorganic acid-binding agent is preferably 1:(1-2), more preferably 1:(0.6-1.2).

[0033] In the present invention, the amine catalyst includes at least one of tetramethylammonium halide, tetra-n-butylammonium halide, tetraalkylammonium halide, phenyltrialkylammonium halide, benzyltrialkylammonium halide, hexadecylmethylammonium halide, dodecylmethylammonium halide, tetramethylammonium perchlorate, tetramethylammonium p-toluenesulfonate, tetra-n-butylammonium perchlorate and tetra-n-butylammonium hydrogen sulfate; the tetramethylammonium halide preferably includes at least one of tetramethylammonium chloride, tetramethylammonium bromide and tetramethylammonium iodide; the tetra-n-butylammonium halide preferably includes at least one of tetra-n-butylammonium chloride, tetra-n-butylammonium bromide and tetra-n-butylammonium iodide; the tetraalkylammonium halide preferably includes tetrapropylammonium bromide, tetra-n-propylammonium iodide, tetra-n-pentylammonium bromide, tetra-n-hexylammonium bromide, tetra-n-heptylammonium bromide ammonium chloride, tetra-n-octylammonium bromide and methyl tri-n-octylammonium chloride; the phenyltrialkylammonium halide preferably includes at least one of phenyltrimethylammonium chloride, phenyltrimethylammonium bromide, phenyltrimethylammonium iodide and phenyltriethylammonium chloride; the benzyltrialkylammonium halide preferably includes at least one of benzyltrimethylammonium chloride, benzyltrimethylammonium bromide, benzyltriethylammonium chloride, benzyltriethylammonium bromide and benzyltri-n-butylammonium; the hexadecylmethylammonium halide preferably includes at least one of hexadecyldimethylammonium chloride, hexadecyltrimethylammonium chloride and hexadecyltrimethylammonium bromide; the dodecylmethylammonium halide preferably includes dodecyltrimethylammonium chloride and / or dodecyltrimethylammonium bromide. In the present invention, the mass of the amine catalyst is preferably 0.1 to 5% of the mass of the SN-1 intermediate, and more preferably 0.5 to 2%.

[0034] In the present invention, the organic solvent preferably includes at least one of a halogenated alkane solvent, a benzene solvent and an ester solvent; the halogenated alkane solvent preferably includes at least one of dichloromethane, dichloroethane and chloroform; the benzene solvent preferably includes at least one of toluene, xylene and trimethylbenzene; the ester solvent preferably includes one or more of ethyl acetate, isopropyl acetate and butyl acetate, more preferably ethyl acetate, isopropyl acetate or butyl acetate. In the present invention, the mass ratio of the SN-1 intermediate to the organic solvent is preferably 1:(0.5-10), more preferably 1:(2-5).

[0035] The present invention has no special limitation on the mixing, and the raw materials can be mixed evenly, such as stirring and mixing. In the present invention, the mixing is preferably: premixing the SN-1 intermediate, the inorganic acid binding agent, the amine catalyst and the organic solvent under reflux conditions, and adding ethyl chloroformate dropwise to the resulting mixed solution. In the present invention, the premixing time is preferably 0.5 to 2 hours, more preferably 1 to 1.5 hours. The present invention has no special limitation on the speed of the dropping, and it can be added dropwise at a uniform speed.

[0036] In the present invention, the temperature of the condensation reaction is preferably 0 to 100° C., more preferably 10 to 60° C. The present invention has no particular limitation on the time of the condensation reaction, subject to the residual amount of the SN-1 intermediate being less than 1%. In the present invention, the reaction formula of the condensation reaction is shown in formula (1):

[0037]

[0038] After the condensation reaction, the present invention preferably further comprises purifying the obtained condensation reaction liquid, and the purification preferably comprises: performing solid-liquid separation on the obtained condensation reaction liquid, mixing the obtained liquid component with water, adjusting the pH value to 3-4, layering, washing the obtained organic phases in sequence, removing the solvent and recrystallizing to obtain spirotetramat. The present invention does not specifically limit the solid-liquid separation method, and can adopt the solid-liquid separation method well known to those skilled in the art, such as filtration. In the present invention, the mass ratio of the liquid component (based on the mass of the SN-1 intermediate) to the added water is preferably 1: (0.5-2), and more preferably 1: (1-1.5). In the present invention, the acid used to adjust the pH value preferably includes hydrochloric acid. In the present invention, the number of water washings is preferably 2-3 times; the mass ratio of the SN-1 intermediate to the water used for a single water washing is preferably 1: (0.5-2), and more preferably 1: (1-1.5). The present invention does not specifically limit the solvent removal method, and can completely remove the solvent in the organic phase, such as vacuum distillation. In the present invention, the recrystallization solvent for recrystallization preferably includes one or more of petroleum ether, n-hexane, n-heptane, toluene, xylene and trimethylbenzene, and more preferably includes petroleum ether, n-hexane, n-heptane, toluene, xylene or trimethylbenzene. The mass ratio of the SN-1 intermediate to the recrystallization solvent is preferably 1: (1 to 5), and more preferably 1: (2 to 3).

[0039] The technical solutions in the present invention will be described clearly and completely below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0040] Example 1

[0041] Add 250 mL of dichloromethane, 60 g of SN-1 intermediate, 9.2 g of sodium hydroxide and 0.6 g of tetrabutylammonium bromide to the reaction bottle, stir under reflux for 1 h, then add 24.8 g of ethyl chloroformate dropwise at 10 ° C. After the addition is completed, keep warm and react until the residual mass of the SN-1 intermediate accounts for less than 1% of the total mass of the SN-1 intermediate. Filter, add 60 g of water to the obtained liquid component, adjust the pH value to 3.5 with hydrochloric acid, stir evenly and let stand for stratification, wash the obtained organic phase with water twice (60 g of water for a single wash), remove the solvent, and then add 120 g of petroleum ether for recrystallization to obtain spirotetramat (white powder, 62.9 g, yield 84.6%, purity 97.2%).

[0042] Example 2

[0043] To the reaction flask, 250 mL of dichloromethane, 60 g of SN-1 intermediate, 7.9 g of sodium hydroxide, 1.7 g of sodium bicarbonate and 0.6 g of phenyltrimethylammonium chloride were added, and the mixture was stirred under reflux for 1 h. The temperature was raised to 60 ° C. and 24.8 g of ethyl chloroformate was added dropwise. After the addition was completed, the reaction was kept warm until the residual mass of the SN-1 intermediate accounted for less than 1% of the total mass of the SN-1 intermediate. Filter, add 60 g of water to the obtained liquid component, adjust the pH value to 3.5 with hydrochloric acid, stir evenly and allow to stand for stratification, wash the obtained organic phase with water twice (60 g of water for a single wash), remove the solvent, and then add 120 g of petroleum ether for recrystallization to obtain spirotetramat (white powder, 64.7 g, yield 87%, purity 98.1%).

[0044] Comparative Example 1

[0045] Spirotetramat was prepared according to the method of Example 1, the only difference from Example 1 being that 9.2 g of sodium hydroxide was replaced with 24 g of triethylamine to obtain spirotetramat (white powder, 61.5 g, yield of 82.7%, purity of 96.5%).

[0046] Figure 1 is the mass spectrum of spirotetramat, the molecular weight of spirotetramat is 373.44, Figure 1 It can be seen that the molecular weight detected by mass spectrometry is 374.19 (M+1 molecular ion peak), indicating that the product is spirotetramat.

[0047] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A method for synthesizing spirotetramat, characterized in that: The following steps are involved: The SN-1 intermediate, ethyl chloroformate, an inorganic acid-binding agent, an amine catalyst and an organic solvent are mixed to carry out a condensation reaction to obtain spirotetramat; The inorganic acid-binding agent is at least one of carbonate, bicarbonate and hydroxide; the carbonate is sodium carbonate and / or potassium carbonate; the bicarbonate is sodium bicarbonate and / or potassium bicarbonate; the hydroxide is at least one of sodium hydroxide, potassium hydroxide and lithium hydroxide; The organic solvent is dichloromethane; the mass ratio of the SN-1 intermediate to the organic solvent is 1:(0.5-5); The amine catalyst is at least one of tetramethylammonium halide, tetra-n-butylammonium halide and phenyltrialkylammonium halide; the phenyltrialkylammonium halide is at least one of phenyltrimethylammonium chloride, phenyltrimethylammonium bromide and phenyltrimethylammonium iodide; After the condensation reaction, the obtained condensation reaction liquid is purified, and the purification includes: solid-liquid separation of the obtained condensation reaction liquid, mixing the obtained liquid component with water, adjusting the pH value to 3-4, layering, and washing the obtained organic phase with water, removing the solvent and recrystallizing in sequence; The molar ratio of the SN-1 intermediate to ethyl chloroformate is 1:(1-1.5); The molar ratio of the SN-1 intermediate to the inorganic acid binding agent is 1:(1-2); The mass of the amine catalyst is 0.5 to 5% of the mass of the SN-1 intermediate; The temperature of the condensation reaction is 10 to 60°C; The recrystallization solvent includes one or more of petroleum ether, n-hexane, n-heptane, toluene, xylene and trimethylbenzene.

2. The synthesis method according to claim 1, characterized in that The tetramethylammonium halide is at least one of tetramethylammonium chloride, tetramethylammonium bromide and tetramethylammonium iodide; The tetra-n-butylammonium halide is at least one of tetra-n-butylammonium chloride, tetra-n-butylammonium bromide and tetra-n-butylammonium iodide.

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