A method for preparing dichlorprop using sulfur hexafluoride

Abstract

The application discloses a method for preparing diethatone by using sulfur hexafluoride, which takes diethylamine and 2-(1-naphthoxy)propionic acid as raw materials, and performs a reaction under the conditions of a photocatalyst, an alkali, sulfur hexafluoride and light irradiation in an organic solvent to obtain diethatone. The method has the characteristics of mild reaction conditions, cheap and easily available reaction raw materials, cost saving, environmental friendliness and industrial promotion. The method effectively activates the greenhouse gas SF6, fully utilizes the decomposition products of SF6 to realize the amidation reaction of 2-(1-naphthoxy)propionic acid, and obtains diethatone, thereby changing waste into treasure, and the required raw materials are simple and easily available. The reaction condition is simple, green, energy-saving, and has high application value.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical synthesis technology, and specifically to a method for preparing dichlorvos using sulfur hexafluoride. Background Technology

[0002] Amide reactions are among the most commonly used organic synthesis reactions. A study on drug synthesis showed that 65% of drug synthesis processes utilize amidation. Furthermore, amidated products play important roles in the biomedical, pharmaceutical, and food industries, and have wide applications in industrial products. For example, thioamides can modify peptide units and proteins; thioamide modification can significantly improve the stability and activity of peptide drugs. Tyramine-derived hydroxycinnamate in plant-based foods, due to its natural antioxidant properties, can be used as a food preservative. Amide greases, due to their excellent thermal stability, radiation resistance, and mechanical stability, are commonly used in nuclear power and aerospace fields. Currently, the synthetic amide compounds include:

[0003] Method 1: Use 3,4,5-trifluorophenylboronic acid as a catalyst to catalyze the amidation reaction of carboxylic acids and amines.

[0004]

[0005] This method is applicable not only to the reaction of primary and tertiary amines with carboxylic acids, but also to some special substrates with large steric hindrance and olefin groups. However, it requires high temperature (>100℃) and anhydrous conditions and suffers from low atom economy.

[0006] Method 2: Using two zirconium catalysts (ZrCp2Cl2 / ZrCl4), under toluene solvent and reflux conditions at 110°C, the amidation reaction of carboxylic acids and amines can be catalyzed efficiently.

[0007]

[0008] This method has high yields and can synthesize two drug molecules, acetaminophen and moclobemide, in relatively high yields. However, it introduces metal compounds and requires high-temperature conditions.

[0009] Method 3: Secondary amides were synthesized by using an active ester as an acyl source and zinc powder as a catalyst under microwave heating in DMF solvent or heating in THF solvent.

[0010]

[0011] This reaction is characterized by its simplicity, high efficiency, environmental friendliness, and reusable catalyst. However, it has a narrow substrate applicability and generates alcohols, which poses significant challenges to the separation of subsequent products.

[0012] Based on the above analysis, there is still a need to develop a carboxylic acid amidation method that uses readily available raw materials, is easy to operate, has a high reaction yield, good functional group tolerance, is environmentally friendly, and is easy to promote in industrial production.

[0013] SF6 gas is a colorless, odorless, non-toxic, non-flammable, and non-corrosive gas at normal temperature and pressure. It is an inert gas with high stability, not decomposing even at high temperatures of 500-600℃, and does not react with acids, alkalis, or water. It is also an insulating gas with excellent insulating properties, used to extinguish high-voltage electric arcs, hence its widespread use in the power industry. However, SF6 has a powerful greenhouse effect, with a global warming potential 23,900 times that of CO2. Furthermore, because SF6 is a synthetic gas with remarkably stable chemical properties, it is extremely difficult to decompose, and its natural atmospheric lifespan can reach over three thousand years. As it accumulates in the atmosphere, its greenhouse effect continues to intensify. Therefore, SF6 emissions are strictly limited, and the large quantities of SF6 stored in the power sector face immense pressure in terms of disposal.

[0014] N,N-Diethyl-2-(α-naphthoxy)propionamide, known as dichlorvos, is commonly marketed under the trade name "Devrinol". It is used for pre-emergence control of annual grasses and broadleaf weeds in many crops and plantations. Application document with publication number IN1303KOL2013A discloses a non-aqueous method for preparing R-(-)-N,N-diethyl-2-(α-naphthoxy)propionamide, comprising the following steps: i. reacting (L)-2-(-)-halopropionic acid with thionyl chloride and a basic compound to generate (L)-2-(+)-halopropionyl chloride; ii. reacting (L)-2-halopropionyl chloride with N,N-diethylamine in the presence of a non-aqueous base and an organic solvent to form (L)-2-(+)-N,N-diethyl-halopropionamide; iii. reacting a substance containing (L)-2-N,N-diethyl-halopropionamide with α-naphthol in the presence of a non-aqueous base to form R-(-)-N,N-diethyl-2-(α-naphthoxy)propionamide. The reaction steps are complex and the reaction temperature is high, limiting its application. Summary of the Invention

[0015] The technical problem to be solved by this invention is how to synthesize dichlorvos in a simple, safe and green way.

[0016] The present invention solves the above-mentioned technical problems through the following technical means:

[0017] A method for preparing dichlorvos using sulfur hexafluoride involves reacting diethylamine and 2-(1-naphthoxy)propionic acid in an organic solvent under the conditions of a photocatalyst, alkali, sulfur hexafluoride, and light to obtain dichlorvos.

[0018] Preferably, the method for preparing dichlorvos using sulfur hexafluoride includes the following steps: adding 2-(1-naphthoxy)propionic acid and a photocatalyst into a reaction apparatus, adding an organic solvent after evacuation, introducing sulfur hexafluoride gas, then adding diethylamine and a base, and placing the reaction system under a light source to react and obtain dichlorvos.

[0019] Preferably, the photocatalyst is one or more of organic photocatalysts or transition metal photocatalysts, or a mixture thereof.

[0020] Preferably, the organic photocatalyst is 4CZIPN, Mes-Acr + ClO4 — One or a mixture of two of (9-trimethylmethyl-10-methylacridinium perchlorate).

[0021] Preferably, the transition metal photocatalyst is one or a mixture of two of Ir[dF(CF3)ppy]2(dtbbpy)PF6 and Ir(dtbbpy)ppy2PF6.

[0022] Preferably, the photocatalyst is Ir[dF(CF3)ppy]2(dtbbpy)PF6.

[0023] Preferably, the organic solvent is one or a mixture of tetrahydrofuran, acetonitrile, and dichloromethane.

[0024] Preferably, the organic solvent is acetonitrile.

[0025] This invention is carried out in a system with a single organic solvent; other organic solvents may be present in the system if necessary, but from the perspective of reaction yield and simplicity of operation, it is preferable not to add other organic solvents, that is, to use a single organic solvent as the reaction solvent.

[0026] Preferably, the alkali is an organic alkali.

[0027] Preferably, the organic base is a tertiary amine.

[0028] Preferably, the base is N,N-diisopropylethylamine. The product yield is highest when the base is N,N-diisopropylethylamine.

[0029] Preferably, the molar ratio of diethylamine to 2-(1-naphthoxy)propionic acid is 1:1 to 20:1.

[0030] Preferably, the molar ratio of diethylamine to 2-(1-naphthoxy)propionic acid is 10:1.

[0031] Preferably, the molar ratio of 2-(1-naphthoxy)propionic acid to photocatalyst is 100:0.2-1; and the molar ratio of 2-(1-naphthoxy)propionic acid to base is 1:1-1:10.

[0032] Preferably, the molar ratio of 2-(1-naphthoxy)propionic acid to base is 1:5.

[0033] Preferably, the molar ratio of 2-(1-naphthoxy)propionic acid to the photocatalyst is 100:0.5.

[0034] Preferably, the illumination uses blue light with a wavelength of 450-480nm as the light source.

[0035] Preferably, blue light with a wavelength of 465nm is used as the light source.

[0036] Preferably, during the reaction process, the SF6 gas pressure is 1 atm, the reaction temperature is 0–50°C, and the reaction time is 5–48 hours.

[0037] Preferably, the product yield is highest when the gas pressure is 1 atm.

[0038] Preferably, the reaction temperature is room temperature and the reaction time is 20 hours.

[0039] Preferably, the ratio of 2-(1-naphthoxy)propionic acid to organic solvent is 0.5–0.1 mmol: 1 mL.

[0040] Preferably, the ratio of 2-(1-naphthoxy)propionic acid to organic solvent is 0.5 mmol: 3 mL; this yields the highest product.

[0041] Preferably, during the reaction, the decomposition products of SF6 are used as condensing agents.

[0042] The advantages of this invention are:

[0043] In this invention, readily available diethylamine and 2-(1-naphthoxy)propionic acid are used as reaction substrates, commercially available Ir[dF(CF3)ppy]2(dtbbpy)PF6 is used as a photocatalyst, and inexpensive and readily available N,N-diisopropylethylamine is used as a base. Under SF6 gas, dichlorfenapyr is synthesized simply and efficiently. This invention features mild reaction conditions, inexpensive and readily available raw materials, cost-effectiveness, environmental friendliness, and industrial applicability. This method effectively activates and utilizes SF6, a greenhouse gas, fully utilizing SF6 decomposition products to achieve the amidation reaction of carboxylic acids to prepare dichlorfenapyr, turning SF6 waste into a valuable resource. The required raw materials are simple and readily available, the reaction conditions are simple, green, and energy-saving, and it has high application value. Attached Figure Description

[0044] Figure 1 The 1H NMR spectrum of (±)N,N-diethyl-2-(naphth-1-yloxy)propionamide described in Example 1 of this invention;

[0045] Figure 2 The image shows the carbon NMR spectrum of (±)N,N-diethyl-2-(naphth-1-yloxy)propionamide described in Example 1 of this invention. Detailed Implementation

[0046] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0047] Unless otherwise specified, all test materials and reagents used in the following examples are commercially available.

[0048] Unless otherwise specified in the embodiments, the techniques or conditions described in the literature in this field or in accordance with the product manual may be followed.

[0049] All raw materials used in the following specific examples are commercially available, and each reagent is purified using methods known in the art when necessary.

[0050] 1 H NMR and 13 All C NMR measurements were performed using a Bruker Avance 400 spectrometer. The test temperature was room temperature, and the solvent was deuterated chloroform. (Reference selection follows.) 1 ¹H NMR: CHCl₃ was 7.260 ppm; 13 C NMR: CHCl3 was 77,000 ppm.

[0051] Example 1

[0052] Synthesis of (±)N,N-diethyl-2-(naphth-1-yloxy)propionamide (dichloramide)

[0053] 108.1 mg of 2-(1-naphthoxy)propionic acid and 2.8 mg of Ir[dF(CF3)ppy]2(dtbbpy)PF6 were added to a 12 mL headspace vial with a PTFE gasket. After evacuation, an SF6 balloon was inserted, followed by the addition of 3.0 mL of anhydrous acetonitrile and bubbling for 3 minutes. Then, 517.3 μL of diethylamine and 434.6 μL of N,N-diisopropylethylamine were added. The reaction system was placed under a 15 W, 465 nm blue LED light source and irradiated and stirred at room temperature for 20 hours, with stirring under SF6 gas at one atmosphere. After the reaction, the organic solvent was removed under vacuum, and (±)N,N-diethyl-2-(naphth-1-yloxy)propionamide was obtained by silica gel column chromatography (petroleum ether:ethyl acetate volume ratio = 3:1). That is, 89.4 mg of racemic dichlorvos was obtained, with a yield of 66%.

[0054] The NMR spectrum of the product (±)N,N-diethyl-2-(naphthalene-1-yloxy)propionamide is as follows: Figure 1 and 2 As shown, the NMR data are as follows: 1 H NMR (400MHz, CDCl3) δ8.31–8.29(m,1H),7.81–7.78(m,1H),7.51–7.43(m,3H),7.35–7.32(m,2H),6.83–6.82(m ,1H),5.12(q,J=6.8Hz,1H),3.62–3.53(m,1H),3.46–3.35(m,3H),1.73(d,J=6.8Hz,1H),1.13–0.98(m,6H)ppm. 13 C NMR (101MHz, CDCl3) δ170.2,153.1,134.5,127.4,126.4,125.7,125.6,125.3,122.0,120.9,105.7,41.0,40.3,17.9,14.1,12.6ppm.

[0055] As shown in Example 1, this invention uses readily available 2-(1-naphthoxy)propionic acid and diethylamine as reaction substrates, commercially available Ir[dF(CF3)ppy]2(dtbbpy)PF6 as a photocatalyst, and inexpensive and readily available N,N-diisopropylethylamine as a base. Under SF6 gas at one atmosphere, at room temperature, and using 15W 465nm blue light as the light source, dichlorvos was synthesized simply and efficiently. This method is a mild, simple, and easily industrially applicable synthesis method for dichlorvos. Furthermore, this method effectively activates and utilizes SF6, a greenhouse gas, and fully utilizes the decomposition products of SF6 to achieve the amidation reaction of carboxylic acids to prepare dichlorvos, turning SF6 waste into a valuable resource.

[0056] Example 2

[0057] Synthesis of (±)N,N-diethyl-2-(naphth-1-yloxy)propionamide (dichloramide)

[0058] 108.1 mg of 2-(1-naphthoxy)propionic acid and 5.6 mg of Ir[dF(CF3)ppy]2(dtbbpy)PF6 were added to a 12 mL headspace vial with a PTFE gasket. After evacuation, an SF6 balloon was inserted, followed by the addition of 2.0 mL of anhydrous tetrahydrofuran and bubbling for 3 minutes. Then, 51.7 μL of diethylamine and 87.5 μL of N,N-diisopropylethylamine were added. The reaction system was placed under a 15 W, 450 nm blue LED light source and irradiated and stirred at room temperature for 48 hours, with stirring under SF6 gas at one atmosphere. After the reaction was completed, the organic solvent was removed under vacuum, and (±)N,N-diethyl-2-(naphth-1-yloxy)propionamide was obtained by silica gel column chromatography (petroleum ether:ethyl acetate volume ratio = 3:1).

[0059] Example 3

[0060] Synthesis of (±)N,N-diethyl-2-(naphth-1-yloxy)propionamide (dichloramide)

[0061] 108.1 mg of 2-(1-naphthoxy)propionic acid and 1.2 mg of Ir[dF(CF3)ppy]2(dtbbpy)PF6 were added to a 12 mL headspace vial with a PTFE gasket. After evacuation, an SF6 balloon was inserted, followed by the addition of 5.0 mL of anhydrous dichloromethane and bubbling for 3 minutes. Then, 1029 μL of diethylamine and 869.2 μL of N,N-diisopropylethylamine were added. The reaction system was placed under a 15 W, 480 nm blue LED light source and irradiated and stirred at room temperature for 5 hours. The stirring was carried out under SF6 gas at one atmosphere. After the reaction was completed, the organic solvent was removed under vacuum, and (±)N,N-diethyl-2-(naphth-1-yloxy)propionamide was obtained by silica gel column chromatography (petroleum ether:ethyl acetate volume ratio = 3:1).

[0062] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for preparing dichlorvos using sulfur hexafluoride, characterized in that: The process involves reacting diethylamine and 2-(1-naphthoxy)propionic acid in an organic solvent under the conditions of a photocatalyst, alkali, sulfur hexafluoride, and light to obtain the chlorpyrifos. The photocatalyst is one or a mixture of two of Ir[dF(CF3)ppy]2(dtbbpy)PF6 and Ir(dtbbpy)ppy2PF6. The light source is blue light with a wavelength of 450-480 nm.

2. The method for preparing dichlorvos using sulfur hexafluoride according to claim 1, characterized in that: The process includes the following steps: adding 2-(1-naphthoxy)propionic acid and a photocatalyst into a reaction apparatus, evacuating the apparatus, adding an organic solvent, introducing sulfur hexafluoride gas, then adding diethylamine and a base, and placing the reaction system under a light source to react and obtain the dichlorvos.

3. The method for preparing dichlorvos using sulfur hexafluoride according to claim 1, characterized in that: The photocatalyst is Ir[dF(CF3)ppy]2(dtbbpy)PF6.

4. The method for preparing dichlorvos using sulfur hexafluoride according to claim 1, characterized in that: The organic solvent is one or more of tetrahydrofuran, acetonitrile, and dichloromethane, or a mixture thereof.

5. The method for preparing dichlorvos using sulfur hexafluoride according to claim 1, characterized in that: The base is N,N-diisopropylethylamine.

6. The method for preparing dichlorvos using sulfur hexafluoride according to claim 1, characterized in that: The molar ratio of diethylamine to 2-(1-naphthoxy)propionic acid is 1:1 to 20:

1.

7. The method for preparing dichlorvos using sulfur hexafluoride according to claim 1, characterized in that: The molar ratio of 2-(1-naphthoxy)propionic acid to photocatalyst is 100:0.2-1; the molar ratio of 2-(1-naphthoxy)propionic acid to base is 1:1-1:

10.

8. The method for preparing dichlorvos using sulfur hexafluoride according to claim 1, characterized in that: During the reaction, the SF6 gas pressure is 1 atm, the reaction temperature is 0~50℃, and the time is 5~48h.

9. The method for preparing dichlorvos using sulfur hexafluoride according to any one of claims 1-8, characterized in that: The ratio of 2-(1-naphthoxy)propionic acid to organic solvent is 0.5~0.1 mmol: 1 mL.

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