Synthesis method and application of 4-chlorobenzothiazolone, a key intermediate of o-aminodisulfide and ethyl benzoate

Abstract

The present invention relates to the field of pesticide synthesis, and specifically, the present invention provides a synthesis method and application of o-aminodisulfide and 4-chlorobenzothiazolone, a key intermediate of ethyl chloramine. The present invention uses 2,6-dichloronitrobenzene, a cheap and easily available industrial product, as an initial substrate to synthesize o-aminodisulfide. The synthesis method of the o-aminodisulfide overcomes the shortcomings of the traditional method, such as many wastes, a complex reaction route, and troublesome post-treatment, and has the advantages of cheap substrate, simple reaction process, mild reaction conditions, etc., and the o-aminodisulfide can be used as an intermediate to efficiently and greenly synthesize 4-chlorobenzothiazolone with hydrogen sulfide and carbon dioxide under mild conditions, and on this basis, 4-chlorobenzothiazolone is reacted with ethyl chloroacetate and potassium carbonate to obtain ethyl chloramine, thereby opening up a new path for synthesizing 4-chlorobenzothiazolone and ethyl chloramine with simpler reaction steps and milder conditions.

Description

Technical Field

[0001] The present invention relates to the field of pesticide synthesis, and in particular, provides a method for synthesizing 4-chlorobenzothiazolone, a key intermediate of o-aminodisulfide and ethyl thiazolin, and application thereof. Background Art

[0002] Ethyl thiocarb is a compound for controlling annual broadleaf weeds. It is mainly used as a professional herbicide in rapeseed fields. It has the characteristics of high efficiency, low toxicity and low residue. It can be quickly degraded in the soil and will not affect subsequent crops. The global annual demand is about 2,000 tons. There are currently no other alternative varieties in the world. The current method for synthesizing ethyl thiocarb is mainly to synthesize 4-chlorobenzothiazolone as the parent core structure and ethyl haloacetate. Among them, 4-chlorobenzothiazolone is an important intermediate, and it is particularly important to explore its synthesis method and intermediates. After reviewing the relevant literature, it is summarized that the traditional synthesis methods of 4-chlorobenzothiazolone mainly include the following:

[0003] Taking o-chloroaniline derivatives as the initial substrate, they can be reacted with carbon disulfide, chlorocarbonylsulfenyl chloride, benzoyl isothiocyanate and other substrates through a series of reactions to obtain 4-chlorobenzothiazolone. However, this type of method has the disadvantages of complex reaction routes and expensive substrates. Taking o-aminobenzenethiol derivatives as the initial substrate, they can react with toxic and harmful carbonylation reagents such as triphosgene, urea, and CO to obtain 4-chlorobenzothiazolone. Taking quinone diimine derivatives as the initial substrate, reacting with thioacetic acid and then ring-closing to obtain 4-chlorobenzothiazolone, but this method has the disadvantages of expensive substrates. Taking a series of 2-substituted benzothiazole derivatives as the initial substrate, they can react with various substrates to obtain 4-chlorobenzothiazolone through diazo method, hydrolysis method, rearrangement and the like. However, this type of method has the disadvantages of harsh reaction conditions and complex reaction routes. In this regard, the present invention constructs a method using 2,6-dichloronitrobenzene, a cheap and readily available industrial product, as an initial substrate, which can react with a sulfur-containing reagent to obtain 4-chloro-o-aminodisulfide, an important intermediate for synthesizing 4-chlorobenzothiazolone. Compared with the traditional method, the method for synthesizing 4-chloro-o-aminodisulfide has the advantages of cheap substrate, simple reaction process, mild reaction conditions, etc. Moreover, the intermediate can be efficiently and greenly synthesized with hydrogen sulfide and carbon dioxide under mild conditions, and on this basis, 4-chlorobenzothiazolone is reacted with ethyl chloroacetate and potassium carbonate to obtain ethyl benzyl alcohol.

[0004] According to previous reports, the traditional method for synthesizing 4-chloro-o-aminodisulfide mainly uses o-chloroaniline derivatives as the initial substrate. The reaction process first forms thiourea, then closes the ring to form 2-aminobenzothiazole, and then opens the ring with potassium hydroxide and reoxidizes it. However, this method has the disadvantages of more waste, complex reaction route, and troublesome post-processing.

[0005] Therefore, the present invention develops a new method for synthesizing 4-chloro-o-aminodisulfide, and synthesizes 4-chlorobenzothiazolone and ethyl benzyl ester on the basis of the method, which has the characteristics of being cheap, green and efficient. Summary of the invention

[0006] The invention aims to provide a synthesis method and application of 4-chlorobenzothiazolone, a key intermediate of o-aminodisulfide and ethyl chlorambucil. The synthesis method of o-aminodisulfide overcomes the shortcomings of a traditional method, such as more wastes, a complex reaction route and troublesome post-treatment, and has the advantages of cheap substrate, simple reaction process, mild reaction conditions and the like. The o-aminodisulfide can be used as an intermediate to react with hydrogen sulfide and carbon dioxide to efficiently and greenly synthesize 4-chlorobenzothiazolone under mild conditions. On this basis, 4-chlorobenzothiazolone is reacted with ethyl chloroacetate and potassium carbonate to obtain ethyl chlorambucil, thereby opening up a new synthesis path of 4-chlorobenzothiazolone and ethyl chlorambucil with simpler reaction steps and milder conditions.

[0007] The first aspect of the present invention is to provide a method for synthesizing o-aminodisulfide, comprising the following steps:

[0008] (1) reacting 2,6-dichloronitrobenzene with a sulfur-containing reagent in an organic solvent to obtain a mixed solution containing 3-chloro-2-nitrobenzene mercaptan;

[0009] (2) reacting the mixed solution containing 3-chloro-2-nitrobenzene mercaptan with hydrogen sulfide for a second reaction, and then contacting the reaction solution obtained in the second reaction with an atmosphere containing oxygen to obtain an o-amino disulfide represented by formula A;

[0010] Alternatively, after step (1), step (2') is performed: the mixed solution containing 3-chloro-2-nitrobenzene mercaptan is purified to obtain 3-chloro-2-nitrobenzene mercaptan, and then 3-chloro-2-nitrobenzene mercaptan is reacted with hydrogen sulfide in an organic solvent (2) in the presence of an organic base (1), and then the reaction solution obtained by the reaction is contacted with an atmosphere containing oxygen to obtain an o-amino disulfide represented by formula A;

[0011] .

[0012] According to some preferred embodiments of the present invention, the sulfur-containing reagent is selected from at least one of alkali metal sulfide salts and alkali metal hydrogensulfide salts, preferably at least one of sodium sulfide, potassium sulfide, sodium hydrogensulfide, and potassium hydrogensulfide.

[0013] According to some preferred embodiments of the present invention, the organic solvent is selected from at least one of DMF (N,N-dimethylformamide), NMP (N-methylpyrrolidone), DMSO (dimethyl sulfoxide), acetonitrile, methanol and ethanol.

[0014] According to some preferred embodiments of the present invention, in step (1), the molar ratio of 2,6-dichloronitrobenzene to the sulfur-containing reagent 1 is 1:(1-5), preferably 1:(3-5).

[0015] According to some preferred embodiments of the present invention, the amount of the organic solvent 1 is 1-5 mL, preferably 1-3 mL, relative to 1 mmol of 2,6-dichloronitrobenzene.

[0016] According to some preferred embodiments of the present invention, the conditions for reaction 1 in step (1) include: a temperature of 25-90 o C, preferably 25-50 o C, and / or, the reaction time is 4-24h, preferably 6-8h; and / or, the pH is 5-7. For pH adjustment, for example, 4 mol / L hydrochloric acid can be used to adjust the initial pH of 10-13 to pH 5-7.

[0017] According to some preferred embodiments of the present invention, reaction 1 is carried out in the absence of a catalyst.

[0018] According to some preferred embodiments of the present invention, when performing step (2), the molar ratio of 2,6-dichloronitrobenzene in step (1) to hydrogen sulfide in step (2) is 1:(1-10), preferably 1:(3-5).

[0019] According to some preferred embodiments of the present invention, the conditions for reaction 2 in step (2) include: a temperature of 50-120 o C, preferably 80-110 o C, and / or, the reaction time is 6-48h, preferably 12-24h.

[0020] According to some preferred embodiments of the present invention, in the reaction of step (2'), the organic base one is at least one of DBU (1,8-diazabicycloundec-7-ene), DBN (1,5-diazabicyclo[4.3.0]-5-nonene), TMG (tetramethylguanidine), Et3N, MTBD (7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene), and TBD (1,5,7-triazabicyclo[4.4.0]dec-5-ene).

[0021] According to some preferred embodiments of the present invention, in the reaction of step (2'), the molar ratio of 3-chloro-2-nitrobenzenethiol to the organic base one is 1:(1-5), preferably 1:(3-4).

[0022] According to some preferred embodiments of the present invention, in step (2'), the molar ratio of 3-chloro-2-nitrobenzenethiol to hydrogen sulfide is 1:(1-10), preferably 1:(3-5).

[0023] According to some preferred embodiments of the present invention, relative to 1 mmol of 3-chloro-2-nitrobenzenethiol, the amount of the second organic solvent is 1-5 ml, preferably 1-3 ml.

[0024] According to some preferred embodiments of the present invention, the second organic solvent is selected from at least one of DMF, NMP, DMSO, acetonitrile, methanol and ethanol.

[0025] According to some preferred embodiments of the present invention, the reaction conditions of step (2') include: a temperature of 60-120 o C, preferably 80-110 o C, and / or, the reaction time is 6-48h, preferably 12-24h.

[0026] According to some preferred embodiments of the present invention, the reaction solutions obtained in step (2) and step (2') contain o-aminothiophenol. When o-aminothiophenol comes into contact with oxygen, it will be oxidized to o-aminodisulfide as shown in formula A.

[0027] The atmosphere containing oxygen in step (2) and step (2') is oxygen or a mixed gas containing oxygen; preferably air. According to some preferred embodiments of the present invention, the atmosphere containing oxygen in step (2) and step (2') is air.

[0028] According to some preferred embodiments of the present invention, the method further comprises a step of post-treating the obtained product after the reaction 2 in step (2) or after the reaction in step (2'); wherein, in the case of carrying out step (2'), the method further comprises a step of post-treating the product obtained in step (1);

[0029] Preferably, the post-treatments each include one or a combination of the following steps: extraction, concentration, and recrystallization. Specifically, the post-treatments described in the examples include but are not limited to the post-treatment (purification) methods described in the examples.

[0030] The second aspect of the present invention provides a method for synthesizing 4-chlorobenzothiazolone, comprising: firstly synthesizing an o-aminodisulfide as shown in formula A using the method described in the first aspect;

[0031] Then, in the presence of an organic base and H2S, the o-amino disulfide is reacted with CO2 to obtain 4-chlorobenzothiazolone.

[0032] The invention provides a method for synthesizing 4-chloro-o-aminodisulfide by using 2,6-dichloronitrobenzene as a substrate and a sulfur-containing reagent, and then synthesizing 4-chlorobenzothiazolone with H2S and CO2, providing a green and efficient route for synthesizing 4-chlorobenzothiazolone, and on this basis, synthesizing ethyl chlorpyrifos, and the invention has strong industrial application value.

[0033] The third aspect of the present invention provides a method for synthesizing ethyl fenthion, comprising: firstly synthesizing an o-aminodisulfide as shown in formula A by the method described in the first aspect;

[0034] Then, in the presence of an organic base and H2S, o-amino disulfide is reacted with CO2 to obtain 4-chlorobenzothiazolone;

[0035] Then, 4-chlorobenzothiazolone is reacted with ethyl chloroacetate to obtain a product containing ethyl benzoate.

[0036] Benzophenone ethyl is a highly efficient, low-toxic, low-residue herbicide, which is mainly synthesized by reacting 4-chlorobenzothiazolone as a parent core structure with ethyl haloacetate. In order to synthesize 4-chlorobenzothiazolone, a key intermediate, the present invention provides a method for synthesizing 4-chlorobenzothiazolone using CO2 as a carbonylation reagent. 2,6-dichloronitrobenzene is first reacted with several sulfur-containing reagents to synthesize an o-aminodisulfide compound, and then reacted with an appropriate amount of H2S and CO2 under mild conditions to synthesize 4-chlorobenzothiazolone. Compared with the traditional method, the present invention selects cheap and easily available 2,6-dichloronitrobenzene as the initial substrate, the reaction steps are simple and the conditions are mild, and the resource utilization of two industrial waste gases, H2S and CO2, is realized at the same time. This technology can not only use efficient and green synthesis of bezophenone ethyl, but also can reasonably utilize two industrial waste gases, hydrogen sulfide and carbon dioxide, for resource utilization, and has significant industrial application value.

[0037] In the second aspect or the third aspect of the present invention, the method of preparing 4-chlorobenzothiazolone or further preparing ethyl chlorpyrifos using the o-amino disulfide shown in formula A as a substrate is a prior art, for example, reference may be made to patent CN 116003344 A previously disclosed by the inventor of the present invention, which will not be described in detail herein.

[0038] As an example, in one embodiment of the present invention, the reaction mechanism of the present invention is:

[0039] Under the condition of no catalyst, 2,6-dichloronitrobenzene Ⅰ and sodium sulfide nonahydrate Ⅱ first react to generate 3-chloro-2-nitrobenzene mercaptan Ⅲ; 3-chloro-2-nitrobenzene mercaptan Ⅲ then reacts with H2S to generate o-aminothiophenol IV; o-aminothiophenol IV is easily oxidized to intermediate disulfide V in the air; intermediate disulfide V then reacts with CO2 and H2S to synthesize intermediate 4-chlorobenzothiazolone VI shown; finally, 4-chlorobenzothiazolone VI reacts with ethyl chloroacetate and potassium carbonate to synthesize ethyl benzyl ester VII;

[0040] ;

[0041] ;

[0042] ;

[0043] ;

[0044] .

[0045] Among them, o-aminothiophenol IV will be rapidly oxidized to o-aminodisulfide V (i.e., the product described in Formula A above) in the air. Therefore, in step (2) or step (2') of the method for synthesizing o-aminodisulfide of the present invention, o-aminodisulfide represented by Formula A can be obtained in one step.

[0046] Compared with the prior art, the present invention has the following beneficial effects:

[0047] The invention uses 2,6-dichloronitrobenzene, a cheap and easily available industrial product, as an initial substrate to synthesize o-aminodisulfide. The synthesis method of o-aminodisulfide overcomes the shortcomings of a traditional method, such as more wastes, a complex reaction route, and troublesome post-treatment, and has the advantages of cheap substrate, simple reaction process, mild reaction conditions, and the like. The o-aminodisulfide can be used as an intermediate to react with hydrogen sulfide and carbon dioxide to efficiently and greenly synthesize 4-chlorobenzothiazolone under mild conditions. On this basis, 4-chlorobenzothiazolone is reacted with ethyl chloroacetate and potassium carbonate to obtain ethyl chlorambucil, thereby opening up a new route for synthesizing 4-chlorobenzothiazolone and ethyl chlorambucil with simpler reaction steps and milder conditions.

[0048] Compared with the traditional method, the present invention selects cheap and easily available 2,6-dichloronitrobenzene as the initial substrate, the reaction steps are simple and the conditions are mild. It can not only efficiently and greenly synthesize ethyl thiocarb, but also reasonably utilize the two industrial waste gases of hydrogen sulfide and carbon dioxide as resources, and has significant industrial application value. DETAILED DESCRIPTION

[0049] The present invention is described in detail below in conjunction with specific embodiments. It is necessary to point out that the following embodiments are only used to further illustrate the present invention and cannot be understood as limiting the scope of protection of the present invention. Some non-essential improvements and adjustments made to the present invention by those skilled in the art based on the contents of the present invention still fall within the scope of protection of the present invention.

[0050] The present invention will be further described below in conjunction with specific examples. It should be understood that these examples are only used to illustrate the present invention and are not intended to limit the scope of the present invention. The experimental methods in the following examples without specifying specific conditions are usually based on conventional conditions or the conditions recommended by the manufacturer. Unless otherwise stated, percentages and parts are calculated by weight.

[0051] In the following examples, unless otherwise specified, the raw materials and equipment used are conventional commercial products; the equipment used are conventional equipment in the art.

[0052] In the following examples, the calculation formula for the yield is:

[0053]

[0054]

[0055]

[0056] The purity of the intermediates and products obtained by purification in the following examples is greater than 99%, wherein the purity is detected by liquid chromatography.

[0057] In the following examples, room temperature refers to an indoor temperature of 25°C.

[0058] Example 1

[0059] 2,6-dichloronitrobenzene and a sulfur-containing reagent are used as raw materials to first synthesize 3-chloro-2-nitrobenzenethiol III, and then 3-chloro-2-nitrobenzenethiol is used as a raw material to synthesize o-aminodisulfide.

[0060] The reaction mechanism is as follows:

[0061]

[0062] Step 1: Place a magnetic bar in a round-bottom flask, accurately weigh 1.0 mmol 2,6-dichloronitrobenzene (0.192 g), 5 mmol sulfur-containing reagent (NaSH), and 2.0 mL DMSO, add them to the round-bottom flask, cover it with a glass cover, and place it in a sand bath. Stir (800 rpm) at room temperature for 8 h, then add 4 mol / L hydrochloric acid to adjust the pH to 5-6, then transfer it to a 250 mL separatory funnel, and use ethyl acetate / saturated brine for positive extraction and back extraction three times. Combine the organic phases and add anhydrous magnesium sulfate to dry for 30 min, filter under reduced pressure to remove the residue, and transfer the filtrate to 100 mL round-bottom flask, use a rotary evaporator to concentrate the reaction solution under reduced pressure distillation, add an appropriate amount of 200-300 mesh silica gel to mix the sample, and perform column chromatography separation and purification. Use petroleum ether and ethyl acetate (50:1-10:1) as gradient elution and monitor the separation by TLC. The mixed solution containing the product is distilled under reduced pressure to obtain the target product 3-chloro-2-nitrobenzenethiol III.

[0063] Step 2: Then put a magnetic bar into a 15 mL stainless steel autoclave, accurately weigh 1.0 mmol 3-chloro-2-nitrobenzenethiol (0.189 g), 2.0 mL DMSO, and 3.0 mmol triethylamine in turn, fill with 5 mmol H2S, tighten the autoclave and put it into a sand bath, stir (800 rpm) at 90°C for 12 h, stop the reaction and take out the autoclave, let it stand for a while to let the autoclave temperature drop to room temperature, at which time the main product in the reaction solution is o-aminothiophenol. Then, exhaust the gas in the autoclave in a fume hood and open the lid of the autoclave, the reaction solution is exposed to oxygen in the air, and the o-aminothiophenol in the reaction solution will be oxidized to o-aminodisulfide. The reaction solution was transferred to a 250 mL separatory funnel using a plastic dropper, and extracted three times with ethyl acetate / saturated brine. The organic phases were combined and dried for 30 min with anhydrous magnesium sulfate. The residue was removed by filtration under reduced pressure. The filtrate was transferred to a 100 mL round-bottom flask. The reaction solution was concentrated by vacuum distillation using a rotary evaporator. An appropriate amount of 200-300 mesh silica gel was added to mix the sample. Column chromatography was performed for separation and purification. The mixture was eluted with a gradient of petroleum ether and ethyl acetate (30:1-10:1) and the separation was monitored by TLC. The mixed solution containing the product was subjected to vacuum distillation to obtain the target product, o-aminodisulfide V, with a yield of 80%.

[0064] Example 2-31

[0065] The o-aminodisulfide V was synthesized by referring to the method of Example 1, except that the conditions of Examples 2-31 are listed in Table 1, and the other conditions not listed are the same as those of Example 1.

[0066] Table 1

[0067]

[0068] Embodiment 32

[0069] O-aminodisulfide V was synthesized by a one-pot two-step method using 2,6-dichloronitrobenzene and a sulfur-containing reagent as raw materials.

[0070] Reaction mechanism:

[0071]

[0072] Step 1: First, place a magnetic bar in a 15 mL stainless steel high-pressure reactor, accurately weigh 1.0 mmol 2,6-dichloronitrobenzene (0.192 g), 5 mmol sulfur-containing reagent (NaSH), and 2.0 mL DMSO and add them to the reactor in sequence, tighten the reactor and place it in a sand bath, stir (800 rpm) at room temperature for 8 h to obtain a reaction mixture;

[0073] Step 2: After 5 mmol H2S is charged into the reaction mixture obtained in the first step, the mixture is stirred (800 rpm) at 90°C for 12 h, the reaction is stopped and the reactor is taken out, and the reactor body is left to stand for a period of time to allow the temperature to drop to room temperature. At this time, the main product in the reaction solution is o-aminothiophenol. Subsequently, the gas in the reactor is discharged in the fume hood and the reactor cover is opened. The reaction solution is exposed to oxygen in the air, and the o-aminothiophenol in the reaction solution is oxidized to o-aminodisulfide. The reaction solution was transferred to a 250 ml separatory funnel using a plastic dropper, and the gas in the autoclave was discharged in a fume hood. The lid of the reactor was opened, and the reaction solution was transferred to a 250 ml separatory funnel. The reaction solution was extracted and back-extracted three times with ethyl acetate / saturated brine. The organic phases were combined and dried for 30 min with anhydrous magnesium sulfate. The residue was removed by filtration under reduced pressure. The filtrate was transferred to a 100 ml round-bottom flask. The reaction solution was concentrated by vacuum distillation using a rotary evaporator. An appropriate amount of 200-300 mesh silica gel was added to mix the sample. The product was separated and purified by column chromatography. The product was eluted with a gradient of petroleum ether and ethyl acetate (30:1-10:1) and the separation was monitored by TLC. The mixed solution containing the product was subjected to vacuum distillation to obtain the target product, o-aminodisulfide V, with a yield of 73%.

[0074] Examples 33-59

[0075] The o-aminodisulfide V was synthesized by referring to the method of Example 32, except that the conditions of Examples 33-59 are listed in Table 2, and the other conditions not listed are the same as those of Example 32.

[0076] Table 2

[0077]

[0078] Embodiment 60

[0079] Synthesis of 4-chlorobenzothiazolone:

[0080]

[0081] A magnetic bar was placed in a 15 mL stainless steel high-pressure reactor, and 1.0 mmol of o-aminodisulfide V (0.316 g), 3.0 mmol of triethylamine, and 2.0 mL of NMP were accurately weighed and added to the reactor in sequence. An appropriate amount of H2S (see Table 3) was charged into the reactor, and the reactor was tightened and placed in a sand bath pot. After stirring (800 rpm) at 90°C for preheating for 30 min, an appropriate amount of CO2 (see Table 3) was charged, and the reactor was tightened again and placed in a sand bath pot. After stirring (800 rpm) at 90°C for reaction for 24 h, the reaction was stopped and the reactor was taken out and allowed to stand for a period of time to allow the reactor temperature to drop to room temperature. The gas in the reactor was discharged in a fume hood, the reactor cover was opened, the reaction solution was transferred to a 250 mL separatory funnel, and ethyl acetate / saturated brine was used for positive and reverse extraction three times. The organic phases were combined and added to anhydrous magnesium sulfate for drying for 30 min. The residue was removed by filtration under reduced pressure, and the filtrate was transferred to a 100 mL round-bottom flask. The reaction solution was concentrated by vacuum distillation using a rotary evaporator, and an appropriate amount of 200-300 mesh silica gel was added to mix the sample. Column chromatography was performed for separation and purification, and petroleum ether and ethyl acetate (30:1-10:1) were used for gradient elution and the separation was monitored by TLC. The mixed solution containing the product was subjected to vacuum distillation to obtain the target product 4-chlorobenzothiazolone VI. The yield is shown in Table 3.

[0082] Examples 61-66

[0083] 4-Chlorobenzothiazolone VI was prepared according to the method of Example 60. The different experimental conditions are listed in Table 3, and the other conditions not listed are the same as those in Example 60.

[0084] Table 3

[0085]

[0086] Embodiment 67

[0087] Synthesis of ethyl benzyl ester:

[0088]

[0089] Place a magnetic bar in a 15 mL stainless steel high-pressure reactor, accurately weigh 1.0 mmol 4-chlorobenzothiazolone, ethyl chloroacetate, and K2CO3 in sequence and add them to the reactor, control the molar ratio of 4-chlorobenzothiazolone:ethyl chloroacetate:K2CO3 to be 1:1.1:0.25, tighten the reactor and place it in a sand bath, stir (800 rpm) at 60°C for 4 h, stop the reaction, take out the reactor, and let it stand for a while to allow the reactor temperature to drop to room temperature. The gas in the reactor was discharged in a fume hood, the lid of the reactor was opened, the reaction solution was transferred to a 250 mL separatory funnel, and positive and reverse extractions were performed three times with ethyl acetate / saturated brine. The organic phases were combined and added to anhydrous magnesium sulfate for drying for 30 min. The residue was removed by suction filtration, and the filtrate was transferred to a 100 mL round-bottom flask. The reaction solution was concentrated by vacuum distillation using a rotary evaporator, and an appropriate amount of 200-300 mesh silica gel was added to mix the sample. Column chromatography was performed for separation and purification, and petroleum ether and ethyl acetate (30:1-10:1) were used for gradient elution. The separation was monitored by TLC. The mixed solution containing the product was subjected to vacuum distillation to obtain the target product, ethyl benzyl ester, with a yield of 88%.

[0090] Embodiment 68

[0091] Ethyl thiocarb was prepared according to the method of Example 68, except that the molar ratio of 4-chlorobenzothiazolone:ethyl chloroacetate:K2CO3 was 1:1.2:0.25. The yield of the target product, ethyl thiocarb, was 93%.

[0092] It is explained here that the method in the embodiment of the present invention has been used to obtain the intermediate and the target product in the reaction formula through analytical detection, specifically:

[0093] 3-Chloro-2-nitro-benzenethiol (III): Wet-packing column and dry-loading column chromatography (200-300 mesh silica gel) separation: Use petroleum ether: ethyl acetate (V / V) = 30:1 as the developing solvent to purify the crude residue to obtain a yellow solid product. 1 H NMR (500 MHz, DMSO, TMS) δ 7.85-7.87 (d, 1H), 7.81-7.85 (d, 1H), 7.69-7.76 (t, 1H), 3.37 (s, 1H); 13 C NMR (126 MHz, DMSO- d 6)δ(ppm) 133.66, 132.96, 132.54, 130.12, 125.07, 124.71, found 189.62.

[0094] 2-Amino-3-chlorobenzenethiol (V): Wet-packing column and dry-loading column chromatography (200-300 mesh silica gel) separation: Use petroleum ether: ethyl acetate (V / V) = 15:1 as the developing solvent to purify the crude residue to obtain a yellow-green solid product. 1 H NMR (500 MHz, DMSO-d6) δ 7.28 (d, J = 7.9Hz, 1 H), 6.90 (d, J = 7.6 Hz, 1 H), 6.44 (t, J = 8.1 Hz, 1 H), 5.57 (s, 2H); 13 C NMR (DMSO-d6, 126 MHz) δ(ppm) 146.04, 134.89, 131.89, 118.47, 118.30,116.87, found 159.63.

[0095] 4-Chlorobenzothiazolone (3-chloro-2-nitrobenzenethiol, VI): Wet-packed column and dry-loaded column chromatography (200-300 mesh silica gel) for separation: Use petroleum ether:ethyl acetate (V / V) = 30:1 as the developing solvent to purify the crude residue to obtain a white solid product. 1 H NMR (500 MHz, CDCl3, TMS) δ(ppm) 9.31 (brs, 1 H), 7.31 (d, 1 H, J = 7.9 Hz), 7.28 (dd, 1 H, J1= 8.2 Hz, J2=1.0 Hz), 7.11 (t, J =8.0 Hz, 1 H); 13 C NMR (Chloroform-d, 125 MHz): δ (ppm) 170.64, 132.86, 126.31,124.90, 123.79,120.91, 116.57, found 185.63.

[0096] Benazolin-ethyl ester (VII): Wet-packing column Dry-loading column chromatography (200-300 mesh silica gel) separation: Use petroleum ether: ethyl acetate (V / V) = 30:1 as the developing solvent to purify the crude residue to obtain a light yellow crystalline product. 1H NMR (500 MHz, CDCl3, TMS): δ (ppm) 7.33(d, J = 7.8 Hz, 1H), 7.25 (d, J = 8.1 Hz, 1 H), 7.07 (t, J = 8.0 Hz, 1 H), 5.14 (s, 2 H), 4.25(q, J = 7.1 Hz, 2 H), 1.28 (t, J = 7.1 Hz, 3 H); 13 C NMR (126 MHz, CDCl3) δ(ppm) 170.13, 167.85, 132.76, 129.02, 124.52, 123.77, 121.43, 116.94, 61.91,45.91, 14.11. LCMS (ESI): m / z calcd for C 11 H 10 ClNO3S [M+Na] + :294.0, found271.0. mp :78-80 ℃.

[0097] It should be noted that the embodiments described above are only used to explain the present invention and do not constitute any limitation to the present invention. The present invention has been described with reference to typical embodiments, but it should be understood that the words used therein are descriptive and explanatory words, rather than restrictive words. The present invention may be modified as specified within the scope of the claims of the present invention, and the present invention may be revised without departing from the scope and spirit of the present invention. Although the present invention described therein relates to specific methods, materials and embodiments, it does not mean that the present invention is limited to the specific examples disclosed therein, on the contrary, the present invention can be extended to all other methods and applications with the same functions.

[0098] All publications, patent applications, patents and other references mentioned in this specification are incorporated herein by reference. Unless otherwise defined, all technical and scientific terms used in this specification have the meanings conventionally understood by those skilled in the art. In the event of a conflict, the definition in this specification shall prevail.

[0099] When this specification uses the prefix "well-known to those skilled in the art", "prior art" or similar terms to introduce materials, substances, methods, steps, devices or components, etc., the objects introduced by the prefix cover those commonly used in the art when this application is filed, but also include those that are not commonly used at present but will become recognized in the art as being suitable for similar purposes.

[0100] The endpoints and any values ​​of the scope disclosed in the present application document are not limited to the precise scope or value, and these scopes or values ​​should be understood to include values ​​close to these scopes or values. For numerical ranges, between the endpoint values ​​of each scope, between the endpoint values ​​of each scope and a separate point value, and between separate point values, one or more new numerical ranges can be combined with each other, and these numerical ranges should be considered as specifically disclosed in this article. Hereinafter, in principle, each technical solution can be combined with each other to obtain a new technical solution, which should also be considered as specifically disclosed in this article.

[0101] In the context of the present specification, any matters or items not mentioned are directly applicable to those known in the art without any changes except those explicitly stated.

[0102] Moreover, any embodiment described in this document may be freely combined with one or more other embodiments described in this document, and the technical solutions or technical ideas formed thereby are deemed to be part of the original disclosure or original record of the present invention, and should not be regarded as new content that has not been disclosed or anticipated in this document, unless a person skilled in the art considers that the combination is obviously unreasonable.

Claims

1. A method for synthesizing o-aminodisulfide, comprising the following steps: (1) reacting 2,6-dichloronitrobenzene with a sulfur-containing reagent in an organic solvent to obtain a mixed solution containing 3-chloro-2-nitrobenzenethiol; the molar ratio of 2,6-dichloronitrobenzene to the sulfur-containing reagent in step (1) is 1:(3-5); (2) reacting the mixed solution containing 3-chloro-2-nitrobenzene mercaptan with hydrogen sulfide for a second reaction, and then contacting the reaction solution obtained in the second reaction with an atmosphere containing oxygen to obtain an o-amino disulfide represented by formula A; ； The sulfur-containing reagent is selected from at least one of sodium sulfide, potassium sulfide, sodium hydrosulfide and potassium hydrosulfide; The organic solvent is selected from at least one of DMF, NMP, DMSO, acetonitrile, methanol and ethanol; The amount of organic solvent 1 is 1-3 mL relative to 1 mmol of 2,6-dichloronitrobenzene; The conditions for reaction 1 in step (1) include: a temperature of 25-50 o C, reaction time is 6-8h; In the case of carrying out step (2), the molar ratio of 2,6-dichloronitrobenzene in step (1) to hydrogen sulfide in step (2) is 1:(3-5); The conditions for reaction 2 in step (2) include: a temperature of 80-100 o C, reaction time is 12-24h.

2. The method according to claim 1, characterized in that: Reaction 1 in step (1) is carried out in the absence of a catalyst.

3. The method according to any one of claims 1 to 2, characterized in that: The reaction solution obtained in step (2) contains o-aminothiophenol; and / or, The oxygen-containing atmosphere in step (2) is air; and / or, The method for synthesizing o-amino disulfide further comprises the step of post-treating the obtained product after carrying out the reaction 2 in step (2); The post-treatments each include one or a combination of the following steps: extraction, concentration, and recrystallization.

4. A method for synthesizing 4-chlorobenzothiazolone, comprising: First, synthesize the o-amino disulfide represented by formula A using the method described in any one of claims 1 to 3; Then, in the presence of an organic base and H2S, the o-amino disulfide is reacted with CO2 to obtain 4-chlorobenzothiazolone.

5. A method for synthesizing ethyl chlorpyrifos, comprising: First, synthesize the o-amino disulfide represented by formula A using the method described in any one of claims 1 to 3; Then, in the presence of an organic base and H2S, o-amino disulfide is reacted with CO2 to obtain 4-chlorobenzothiazolone; Then, 4-chlorobenzothiazolone is reacted with ethyl chloroacetate to obtain a product containing ethyl benzoate.

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