Clethodim sulfoxide and its synthesis method and application

Abstract

Clethodim sulfoxide, its synthesis method, and applications relate to the field of chemical synthesis technology. The aforementioned method for synthesizing clethodim sulfoxide uses clethodim and sodium periodate as reaction materials and produces clethodim sulfoxide through an oxidation reaction. This method for synthesizing clethodim sulfoxide is simple, low-cost, high-purity (reaching over 97%), and high-yield (reaching over 93%). Furthermore, clethodim sulfoxide is a metabolite of clethodim. The synthesized standard of clethodim sulfoxide can facilitate the detection of herbicide and metabolite residues in agricultural products and herbal medicines, enhancing quality control and improving their safety.

Description

Technical Field

[0001] The present invention relates to the technical field of chemical synthesis, and in particular to clethodim sulfoxide, a synthesis method thereof and an application thereof. Background Art

[0002] Clethodim is a cyclohexenone herbicide with low toxicity. Its half-life in soil is 3-26 days, its long-lasting effect is short, and it has no effect on subsequent crops. It is suitable for weed control in fields of over 40 crops, including soybeans, flax, tobacco, and watermelon. It can control over 30 grass weeds, including barnyard grass, and is widely used on fruit trees, vegetables, and non-arable land. Clethodim sulfoxide, a metabolite of clethodim, is widely used in agriculture. It is not only used as a herbicide and weed killer, but its standard can also serve as a pesticide residue reference material for pesticide determination. However, the current lack of a synthetic method for clethodim sulfoxide has limited its development. Summary of the Invention

[0003] The technical problem to be solved by the present invention is to provide a method for synthesizing clethodim sulfoxide.

[0004] In order to achieve the above object, the present invention adopts the following technical solutions:

[0005] The invention discloses a method for synthesizing clethodim sulfoxide, which uses clethodim and sodium periodate as reaction raw materials and generates clethodim sulfoxide through an oxidation reaction.

[0006] Among them, the structural formula of clethodim is: The double bond has two configurations: E and Z.

[0007] Among them, the structural formula of sodium periodate is:

[0008] Wherein, clethodim sulfoxide is synthesized according to the following synthetic route:

[0009]

[0010] Preferably, the synthesis method of the above-mentioned clethodim sulfoxide comprises the following steps:

[0011] 1. Stirring an appropriate amount of clethodim and a solvent in an ice-water bath, then adding an appropriate amount of an aqueous solution of sodium periodate and continuing to stir to produce a primary product;

[0012] 2. Separate and purify the initial product generated in step 1 to obtain clethodim sulfoxide.

[0013] The molar ratio of clethodim to sodium periodate may be 1:(2-5), and preferably the molar ratio of clethodim to sodium periodate is 1:3.

[0014] Preferably, in step 1, the solvent may be water, methanol, ethanol, isopropanol or a mixed solvent thereof, that is, the solvent may be one or more of water, methanol, ethanol and isopropanol.

[0015] Preferably, in step 1, the reaction temperature is 0°C.

[0016] Preferably, in step 1, the reaction time is not particularly limited, and is generally 4 to 6 hours (preferably 4 to 5 hours).

[0017] The specific steps of step one are as follows:

[0018] Put clethodim in a three-necked flask, add solvent, and stir in an ice-water bath until completely dissolved. Add an aqueous solution of sodium periodate dropwise to the stirred solution. After the addition is complete, continue stirring in an ice-water bath for five hours.

[0019] Preferably, in step 2, separation and purification comprises the following steps:

[0020] (1) extracting the initial product generated in step 1 and combining the organic layers, then washing, absorbing water, filtering, and spin-drying to obtain a crude product;

[0021] (2) Using silica gel as the stationary phase and dichloromethane and methanol as the mobile phase, the crude product is passed through the column to obtain clethodim sulfoxide.

[0022] The ratio of dichloromethane to methanol in the mobile phase can be 50:1.

[0023] The specific steps of step 2 are as follows:

[0024] The initial product of step 1 was poured into a separatory funnel, and water and ethyl acetate were added for extraction. The aqueous layer was then extracted three times with ethyl acetate. The organic layers were combined and washed twice with an equal amount of saturated brine. The plate was spotted and the product was found in the organic layer. The obtained organic layer was absorbed with dry anhydrous sodium sulfate, filtered, and dried under reduced pressure on a rotary evaporator to obtain a crude product. The crude product was passed through a column using silica gel as the stationary phase and dichloromethane and methanol in a ratio of 50:1 as the mobile phase. After passing through the column, clethodim sulfoxide was obtained.

[0025] Another object of the present invention is to provide clethodim sulfoxide, which is prepared using the above-described method for synthesizing clethodim sulfoxide.

[0026] In addition, the above-mentioned clethodim sulfoxide can also be used in detecting the residual amount of herbicides and their metabolites in agricultural products and herbs.

[0027] In addition, the above-mentioned clethodim sulfoxide can also be used in herbicides.

[0028] In addition, the above-mentioned clethodim sulfoxide can also be used as a pesticide residue standard substance.

[0029] The invention uses clethodim and sodium periodate as raw materials to carry out an oxidation reaction to generate clethodim sulfoxide. The process is simple, the cost is low, and the advantages include high purity (which can reach more than 97%) and high yield (which can reach more than 93%). In addition, clethodim sulfoxide is one of the metabolites of clethodim. The synthesized standard product of clethodim sulfoxide can facilitate the detection of the residual amount of herbicides and their metabolites in agricultural products and herbal medicines, thereby strengthening the quality control of agricultural products and herbal medicines and improving their safety. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 This is the hydrogen nuclear magnetic resonance spectrum of clethodim sulfoxide;

[0031] Figure 2 This is the C-NMR spectrum of clethodim sulfoxide;

[0032] Figure 3 This is the high-resolution mass spectrum of clethodim sulfoxide. DETAILED DESCRIPTION

[0033] To facilitate understanding by those skilled in the art, the present invention is further described below with reference to the examples, which are not intended to limit the present invention. It should be noted in advance that the following examples were performed in the laboratory, and those skilled in the art should understand that the amounts of the components given in the examples merely represent the ratios between the components, and are not intended to be specific limitations.

[0034] Clethodim sulfoxide is one of the metabolites of clethodim. The standard product of synthesizing clethodim sulfoxide is convenient for detecting the residual amount of herbicides and their metabolites in agricultural products and herbs, strengthening the quality control of agricultural products and herbs, and improving their safety. However, there is currently no synthesis method of clethodim sulfoxide. Therefore, the present invention provides a synthetic route for the efficient and rapid synthesis of clethodim sulfoxide by oxidizing clethodim with sodium periodate. Specific details are as follows.

[0035] Example 1:

[0036] Synthesis of Clethodim sulfoxide:

[0037]

[0038] Add a stirring bar to a flame-dried 250ml three-necked flask. Accurately weigh 1.0105g of clethodim and 50ml of methanol into the flask. Insert a rubber stopper and place the flask in an ice-water bath. Stir until the temperature reaches 0°C. Accurately weigh 1.7833g of sodium periodate into a beaker. Add 10ml of water and stir until dissolved. Slowly add the sodium periodate aqueous solution dropwise to the flask. After the addition is complete, continue stirring in the ice-water bath for 5 hours. After 5 hours, a mixture of a light yellow transparent solution and a milky white, tofu-like solid will be obtained.

[0039] Pour the mixture into a separatory funnel and extract with 40 ml of water and 40 ml of ethyl acetate. Extract the aqueous layer three times with 40 ml of ethyl acetate. Combine the organic layers. Wash the organic layer twice with an equal amount of saturated brine. Add dry anhydrous sodium sulfate to absorb the water and filter. Pour the organic layer solution into a single-necked flask and remove the ethyl acetate solvent on a rotary evaporator to obtain a crude product.

[0040] The crude product was passed through a column using silica gel as the stationary phase and dichloromethane:methanol = 50:1 as the mobile phase to obtain clethodim sulfoxide. The product was a brown, viscous liquid with a total weight of 0.9513 g, a calculated yield of 94%, and a purity of 97%.

[0041] The H NMR spectrum data of the obtained product are as follows:

[0042] 1 H NMR(500MHz,Chloroform-d)δ14.25(brs,1H),6.32(d,J=13.4Hz,1H),6.08(dt,J=13.4,6.7H z,1H),4.51(d,J=6.8Hz,2H),2.88-2.84(m,2H),2.77–2.53(m,5H),2.40–2.16(m,3H),2.01–

[0043] 1.71(m,2H),1.34(dt,J=15.6,7.5Hz,3H),1.23(dd,J=20.3,6.8Hz,3H),1.11(t,J=7.4Hz,3H).

[0044] The carbon NMR spectrum data of the obtained product are as follows:

[0045] 13C NMR(126MHz,Chloroform-d)δ165.38,127.57,122.49,122.47,106.92,71.1 7,49.39,41.24,41.11,35.26,28.37,20.07,12.25,10.12,9.76,6.65,6.01.

[0046] The mass spectrum data of the obtained product are as follows:

[0047] MS:Cald.for C 17 H 27 ClNO4S(M+H):376.1349,test 376.2017

[0048] Among them, Figure 1-3 They are respectively the hydrogen nuclear magnetic resonance spectrum, carbon nuclear magnetic resonance spectrum and high-resolution mass spectrum of the obtained product.

[0049] The product obtained in this embodiment is clethodim sulfoxide.

[0050] Example 2:

[0051] Synthesis of Clethodim sulfoxide:

[0052]

[0053] Add a stirring bar to a flame-dried 100ml three-necked flask. Accurately weigh 0.0997g of clethodim and 5ml of methanol into the flask. Insert a rubber stopper and place the flask in an ice-water bath. Stir until the temperature reaches 0°C. Accurately weigh 0.1783g of sodium periodate into a beaker. Add 1ml of water and stir until dissolved. Slowly add the sodium periodate aqueous solution dropwise to the flask. After the addition is complete, continue stirring in the ice-water bath for 5 hours. After 5 hours, a milky yellow, opaque solution will be obtained.

[0054] Pour the solution into a separatory funnel and extract with 10 ml of water and 10 ml of ethyl acetate. Extract the aqueous layer three times with 10 ml of ethyl acetate. Combine the organic layers. Wash the organic layer twice with an equal amount of saturated brine. Add dry anhydrous sodium sulfate to absorb the water and filter. Pour the organic layer solution into a single-necked flask and remove the ethyl acetate solvent on a rotary evaporator to obtain the crude product.

[0055] The crude product was passed through a column using silica gel as the stationary phase and dichloromethane:methanol = 50:1 as the mobile phase to obtain clethodim sulfoxide. The product was a brown, viscous liquid with a total weight of 0.9493 g, a calculated yield of 95%, and a purity of 97%.

[0056] Example 3:

[0057] Synthesis of Clethodim sulfoxide:

[0058]

[0059] Add a stirring bar to a flame-dried 250ml three-necked flask. Accurately weigh 3.006g of clethodim and 40ml of methanol into the flask, plug it with a rubber stopper, and place the flask in an ice-water bath. Stir until the temperature reaches 0°C. Accurately weigh 5.3424g of sodium periodate into a beaker, add 30ml of water, and heat and stir in a 40°C waterbath until the sodium periodate is completely dissolved. Slowly add the sodium periodate aqueous solution dropwise to the flask. After the addition is complete, continue stirring in the ice-water bath for 5 hours. After 5 hours, a mixture of a transparent light yellow solution and a milky white, tofu-like solid will be obtained.

[0060] The reaction mixture was filtered to obtain a clear yellow solution. This solution was poured into a separatory funnel and extracted with 100 ml of water and 50 ml of ethyl acetate. The aqueous layer was then extracted three times with 50 ml of ethyl acetate. The organic layers were combined. The organic layer was washed twice with an equal amount of saturated brine, then dried anhydrous sodium sulfate was added to absorb the water and filtered. The organic layer solution was poured into a single-necked flask and the ethyl acetate solvent was removed on a rotary evaporator to obtain a crude product.

[0061] The crude product was passed through a column using silica gel as the stationary phase and dichloromethane:methanol = 50:1 as the mobile phase to obtain clethodim sulfoxide. The product was a brown, viscous liquid with a total weight of 2.7957 g, a calculated yield of 93%, and a purity of 98%.

[0062] In summary, the method for synthesizing clethodim sulfoxide of the present invention is simple to operate, has mild reaction conditions, requires a short time, and has a high yield. Moreover, it can be clearly seen from all the above examples that the use of a suitable organic solvent (such as methanol) can enable clethodim and sodium periodate to be synthesized with high yield (more than 93%) and high purity (more than 97%) under stirring in an ice-water bath to obtain clethodim sulfoxide. The present invention provides a synthetic route for the efficient and rapid synthesis of clethodim sulfoxide.

[0063] The above embodiments are preferred implementation schemes of the present invention. In addition, the present invention can also be implemented in other ways. Any obvious replacement without departing from the concept of the present technical solution is within the scope of protection of the present invention.

[0064] Finally, it should be emphasized that in order to make it easier for those skilled in the art to understand the improvements of the present invention over the prior art, some descriptions of the present invention have been simplified, and for the sake of clarity, some other elements have been omitted in this application document. Those skilled in the art should realize that these omitted elements may also constitute the content of the present invention.

Claims

1. A method for synthesizing clethodim sulfoxide, characterized in that: Clethodim and sodium periodate are used as reaction materials to generate clethodim sulfoxide through oxidation reaction; The synthetic method synthesizes clethodim sulfoxide according to the following synthetic route: ； The structural formula of the clethodim is: , where the double bond contains two configurations: E and Z; The structural formula of the sodium periodate is: ; The synthesis method comprises the following steps:

1. Stir an appropriate amount of clethodim and methanol in an ice-water bath, then add an appropriate amount of sodium periodate aqueous solution and continue stirring to generate a primary product; 2. separating and purifying the initial product generated in step 1 to obtain clethodim sulfoxide; In step 1, the molar ratio of clethodim to sodium periodate is 1:3; In step 1, the reaction temperature is 0°C and the reaction time is 5 hours.

2. The method for synthesizing clethodim sulfoxide according to claim 1, wherein In step 2, separation and purification include the following steps: (1) extracting the initial product generated in step 1 and combining the organic layers, then washing, absorbing water, filtering, and spin-drying to obtain a crude product; (2) Using silica gel as the stationary phase and dichloromethane and methanol as the mobile phase, the crude product was passed through the column to obtain clethodim sulfoxide.

Images