Synthesis method of diafenthiuron

Abstract

The invention is a divisional application with the application number of 202410786126. X. The invention discloses a synthetic method of diafenthiuron. The method comprises the following steps: in the presence of organic alkali, carrying out condensation reaction on a compound shown in a formula (I) and a compound shown in a formula (II) to obtain diafenthiuron. The diafenthiuron is prepared through condensation of the compound shown in the formula (I) and the compound shown in the formula (II) in the presence of the organic base, and the conversion rate and selectivity are high. Compared with a sodium thiocyanate method, the method provided by the invention has the advantages that the process steps are short, high-temperature thermal decomposition reaction is avoided, the process safety is improved, and the method is suitable for industrial production and has a wide application prospect.

Description

[0001] The present invention is a divisional application of a Chinese application with an application date of June 18, 2024, an application number of 202410786126.X, and an invention name of “A method for synthesizing dibutyl ether urea”. Technical Field

[0002] The invention relates to the field of pesticides, and in particular to a method for synthesizing diafenthiuron. Background Art

[0003] Difenthiuron, chemically named 1-tert-butyl-3-(2,6-diisopropyl-4-phenoxyphenyl)thiourea, is a new type of thiourea insecticide and acaricide. There are several main methods for the synthesis of difenthiuron: thiophosgene method, trimerization method and sodium thiocyanate method, among which the sodium thiocyanate method is the most commonly used method in industrialization. This method uses 4-bromo-2,6-diisopropylaniline as raw material, first reacts with bromine to generate 4-bromo-2,6-diisopropylaniline, then reacts with phenol and alkali to generate 4-phenoxy-2,6-diisopropylaniline, and then condenses with NaSCN to generate substituted thiourea (i.e. 4-phenoxy-2,6-diisopropylphenylthiourea), and finally thermally decomposes (thermal decomposition temperature is generally around 150°C) to obtain isothiocyanate, and finally reacts with tert-butylamine to obtain the target product.

[0004] However, the sodium thiocyanate method for preparing diafenthiuron still has technical defects such as long process route, harsh reaction conditions and high cost. In order to overcome the above technical problems of the method for preparing diafenthiuron in the prior art, a new method for preparing diafenthiuron is needed. Summary of the invention

[0005] Purpose of the Invention

[0006] In order to overcome the above-mentioned shortcomings, the object of the present invention is to provide a method for synthesizing diafenthiuron, wherein the compound represented by formula (I) is condensed with the compound represented by formula (II) in the presence of an organic base or an organic carboxylic acid to prepare diafenthiuron, and the conversion rate and selectivity are high. The method of the present invention is different from the existing sodium thiocyanate route, and avoids the use of dangerous reagents such as sodium thiocyanate. In addition, compared with the sodium thiocyanate method, the method provided by the present invention has short process steps, avoids high-temperature thermal decomposition reaction, improves process safety, is suitable for industrial production, and has broad application prospects. The method of the present invention has the advantages of mild reaction conditions, short process route, high conversion rate and selectivity.

[0007] Solution

[0008] To achieve the purpose of the present invention, the technical solution adopted by the present invention is as follows:

[0009] The present invention provides a method for synthesizing diafenthiuron, which comprises: in the presence of an organic acid or an organic base, subjecting a compound represented by formula (I) to a condensation reaction with a compound represented by formula (II) to obtain diafenthiuron;

[0010]

[0011] In the first aspect, in the presence of an organic acid, the compound represented by formula (I) and the compound represented by formula (II) are subjected to a condensation reaction to obtain diafenthiuron.

[0012] Optionally, when an organic acid is present, the organic acid is a weak organic acid;

[0013] Optionally, the organic acid has a pKa of ≥3.5 in water at 25° C., preferably a pKa of 3.5-5.0 (may be 3.5, 3.8, 4.0, 4.2, 4.5, 4.6, 4.7, 4.8, 5.0 and any value therebetween);

[0014] Optionally, the organic acid is a C1-C10 organic carboxylic acid or an organic sulfonic acid, optionally a C1-C7 organic carboxylic acid or an organic sulfonic acid, optionally a C2-C7 organic carboxylic acid or an organic sulfonic acid;

[0015] Optionally, the organic acid is an organic carboxylic acid with a chemical formula of R1COOH; optionally, R1 is one or more of a hydrogen group, a C1-C9 alkyl group, a C1-C9 hydroxyl-substituted alkyl group, a C1-C9 amino-substituted alkyl group, a phenyl group, and a substituted phenyl group; optionally, R1 is one or more of a hydrogen group, a C1-C5 alkyl group, a C1-C5 hydroxyl-substituted alkyl group, a phenyl group, and a hydroxyl-substituted phenyl group; optionally, R1 is one or more of a hydrogen group, a C1-C3 alkyl group, a C1-C3 hydroxyl-substituted alkyl group, a phenyl group, and a hydroxyl-substituted phenyl group; optionally, R1 is one or more of a hydrogen group, a C1-C2 alkyl group, a C1-C2 hydroxyl-substituted alkyl group, a phenyl group, and a hydroxyl-substituted phenyl group;

[0016] Optionally, the organic acid is selected from one or more of formic acid, acetic acid, propionic acid, lactic acid, benzoic acid, trifluoroacetic acid, isobutyric acid, citric acid and p-toluenesulfonic acid;

[0017] Optionally, the organic acid is selected from one or more of formic acid, acetic acid, propionic acid, lactic acid and benzoic acid.

[0018] Further, when an organic acid is present, the molar ratio of the compound represented by formula (I) to the organic acid is 1:(1-10) (optionally 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10 and any value therebetween), optionally 1:(2-10), optionally 1:(3-10), optionally 1:(2-8), optionally 1:

[0019] (2-5), optionally 1:(3-5).

[0020] Optionally, when an organic acid is present, the condensation temperature is 30-100°C (may be 30°C, 40°C, 50°C, 60°C, 70°C, 80°C, 90°C, 100°C and any value therebetween), optionally 40-90°C (may be 40°C, 50°C, 60°C, 70°C, 80°C, 90°C and any value therebetween), optionally 40-80°C, optionally 40-75°C, optionally 40-70°C, optionally 50-80°C, optionally 50-70°C (may be 50°C, 55°C, 60°C, 65°C, 70°C and any value therebetween).

[0021] Optionally, when an organic acid is present, the reaction time of the condensation is 5-20 h, optionally 5-18 h, optionally 8-18 h, optionally 8-15 h.

[0022] Optionally, when an organic acid is present, the molar ratio of the compound represented by formula (I) to the compound represented by formula (II) is 1:(1-10), optionally 1:(2-10), optionally 1:(3-10), optionally 1:(2-8), optionally 1:(2-5), optionally 1:(3-6), optionally 1:(4-6).

[0023] Alternatively, when an organic acid is present, the condensation reaction is carried out in the absence of a solvent.

[0024] In a second aspect, in the presence of an organic base, the compound represented by formula (I) and the compound represented by formula (II) are subjected to a condensation reaction to obtain diafenthiuron.

[0025] Furthermore, when an organic base exists, the organic base is a strong organic base.

[0026] Optionally, the organic base has a pKa of 8-25 in DMSO at 25° C. (can be 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 and any value therebetween).

[0027] Optionally, the organic base is selected from at least one of N-alkylimidazole, aliphatic amine strong base, bicyclic amidine strong base, pyridine and substituted pyridine.

[0028] Optionally, the alkyl group in the N-alkylimidazole is selected from a C1-C6 alkyl group, and is optionally at least one of a methyl group, an ethyl group, and a propyl group.

[0029] Optionally, the fatty amine strong base is a C2-C14 fatty amine, optionally a C6-C14 fatty amine, optionally one or more of triethylenediamine, triethylamine, and N,N-diisopropylethylamine.

[0030] Optionally, the bicyclic amidine strong base is a C2-C10 bicyclic amidine strong base, and optionally is 1,8-diazabicyclo[5.4.0]undec-7-ene.

[0031] Optionally, the substituent of the substituted pyridine is a C1-C5 alkyl group or a hydroxyl group.

[0032] Optionally, the organic base is selected from at least one of N-methylimidazole, N-ethylimidazole, N-propylimidazole, 1,8-diazabicyclo[5.4.0]undec-7-ene, triethylenediamine, triethylamine, N,N-diisopropylethylamine, 2-hydroxypyridine, 2,6-lutidine and pyridine; wherein,

[0033] Optionally, the organic base is selected from at least one of N-methylimidazole, N-ethylimidazole, N-propylimidazole, 1,8-diazabicyclo[5.4.0]undec-7-ene and triethylenediamine.

[0034] Further, when an organic base is present, the molar ratio of the compound represented by formula (I) to the organic base is 1:(0.1-10) (optionally 1:0.1, 1:0.2, 1:0.5, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10 and any value therebetween), optionally 1:(0.2-5), optionally 1:(0.2-3), optionally 1:(1-5), optionally 1:(1-3), optionally 1:(1.5-3).

[0035] Further, when an organic base is present, the condensation temperature is 30-100°C (can be 30°C, 40°C, 50°C, 60°C, 70°C, 80°C, 90°C, 100°C and any value therebetween), optionally 40-90°C, optionally 40-80°C, optionally 40-75°C, optionally 40-60°C, optionally 45-60°C (can be 40°C, 45°C, 50°C, 55°C, 60°C and any value therebetween), optionally 45-55°C, optionally 45-50°C.

[0036] Furthermore, when an organic base is present, the reaction time of the condensation is 1-20 h, optionally 5-18 h, optionally 8-18 h, optionally 8-15 h.

[0037] Further, when an organic base is present, the molar ratio of the compound represented by formula (I) to the compound represented by formula (II) is 1:(1-10), optionally 1:(2-10), optionally 1:(3-10), optionally 1:(2-8), optionally 1:

[0038] (2-5), optionally 1:(3-6), optionally 1:(4-6).

[0039] Furthermore, when an organic base is present, the condensation reaction is carried out in the absence of a solvent.

[0040] In the present invention, whether the condensation reaction is carried out in the presence of an organic carboxylic acid or an organic base, a small amount of by-product 4-phenoxy-2,6-diisopropylphenyl isothiocyanate will be produced.

[0041] Furthermore, after the condensation reaction, the target product is precipitated, washed with an organic solvent and / or water, and dried to obtain diafenthiuron.

[0042] In the present invention, the target product can be purified by referring to the conventional methods in the art. Preferably, it can be carried out in the following manner: the material containing the compound represented by formula (I) is slurried with an organic solvent and vacuum dried at 50-70°C to constant weight. The organic solvent for slurry washing can be selected from C1-C10 saturated monohydric alcohols and / or water, such as methanol, ethanol, propanol, isopropanol. The present invention has no particular limitation on the amount of organic solvent for slurry washing, as long as it can meet the requirements of the present invention.

[0043] Optionally, the method for precipitating the target product is: recovering the compound represented by formula (II) by vacuum distillation (which can be recovered and reused), and precipitating the target product solid. Optionally, the temperature of the vacuum distillation can be 50-70°C.

[0044] Beneficial Effects

[0045] The present invention prepares diafenthiuron by condensing the compound represented by formula (I) with the compound represented by formula (II) in the presence of an organic base or an organic carboxylic acid, and the conversion rate and selectivity are high. The method of the present invention is different from the existing sodium thiocyanate route, and avoids the use of dangerous reagents such as sodium thiocyanate. In addition, compared with the sodium thiocyanate method, the method provided by the present invention has short process steps, avoids high-temperature thermal decomposition reaction, improves process safety, is suitable for industrial production, and has broad application prospects. The method of the present invention has the advantages of mild reaction conditions, short process route, high conversion rate and selectivity. DETAILED DESCRIPTION

[0046] In order to make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution in the embodiments of the present invention will be described clearly and completely below. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. 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.

[0047] In addition, in order to better illustrate the present invention, numerous specific details are provided in the specific embodiments below. It should be understood by those skilled in the art that the present invention can be implemented without certain specific details. In some embodiments, raw materials, schemes, methods, means, etc. well known to those skilled in the art are not described in detail, so as to highlight the main purpose of the present invention.

[0048] Unless explicitly stated otherwise, throughout the specification and claims, the term “comprise” or variations such as “include” or “comprising”, etc., will be understood to include the stated elements or components but not to exclude other elements or components.

[0049] The endpoints and any values ​​of the ranges disclosed in this article are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of each range, the endpoint values ​​of each range and the individual point values, and the individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed in this article.

[0050] The present invention will be described in detail below through examples.

[0051] In the present invention, there is no particular limitation on the preparation method of the compound represented by formula (I) or formula (II), and the compound can be prepared by referring to conventional methods in the art. For example, the compound represented by formula (I) or the compound represented by formula (II) can be prepared by referring to a published method, or can be commercially available.

[0052]

[0053] In the following examples, unless otherwise specified, all raw materials used were commercially available.

[0054] The contents (purity) of reactants and products were measured by GC.

[0055] The conversion and selectivity of the reaction were calculated by the following formula:

[0056] Conversion rate = (molar amount of raw material input - molar amount of raw material remaining in the product) / molar amount of raw material input × 100%. The conversion rates in the following examples refer to the conversion rates of the compounds of formula (I).

[0057] The selectivity of the target product = the actual molar amount of the target product / the theoretical molar amount of the target product × 100%. The theoretical molar amount of the target product refers to the theoretical value of the target product calculated based on the raw material conversion rate. For example, if the molar amount of the input raw material is 1 mol and the molar amount of the raw material remaining after the reaction is 0.2 mol, then the theoretical molar amount of the target product = ((1-0.2) / 1) × 1 = 0.8 mol, and the actual molar amount of the target product is 0.72 mol, then the selectivity of the target product = (0.72 / 0.8) × 100% = 90%.

[0058] The following examples are used to illustrate the synthesis of diafenthiuron using the method of the present invention:

[0059] In a first aspect, the present invention provides a method for synthesizing diafenthiuron, comprising: in the presence of an organic carboxylic acid, bringing a compound represented by formula (I) (4-phenoxy-2,6-diisopropylaniline) into first contact with a compound represented by formula (II) (tert-butyl isothiocyanate) to produce a condensation reaction to prepare diafenthiuron. Some embodiments are shown in Examples A1 to A10.

[0060]

[0061] Example A1

[0062] (1) 4-phenoxy-2,6-diisopropylaniline (13.5 g, 0.05 mol) and tert-butyl isothiocyanate (23.0 g, 0.2 mol) were added to a 150 mL single-necked round-bottom flask, and acetic acid (12 g, 0.2 mol) was added. The temperature was raised to 70° C. and stirred for condensation reaction for 13 h. HPLC analysis showed that the conversion rate of 4-phenoxy-2,6-diisopropylaniline was 99.5% and the selectivity was 97.3% (butylether urea was the product and 4-phenoxy-2,6-diisopropylphenyl isothiocyanate was the by-product).

[0063] (2) Tert-butyl isothiocyanate was recovered by vacuum distillation at 60°C, and the residual solid was washed with 60 mL of isopropanol and 60 mL of water, filtered, and vacuum dried at 60°C to constant weight to obtain 17.3 g of off-white solid with a yield of 90%.

[0064] The present invention also studies the influence of factors such as the type, amount, reaction temperature or reaction time of organic carboxylic acid, as shown in Examples A2-A10 and Comparative Example 1 in the following table. The operating steps of Examples A2-A10 and Comparative Example 1 are the same as those of Example A1, except that the materials used (type and amount of organic carboxylic acid) and reaction conditions (reaction temperature or reaction time) are different. The specific differences are shown in Table 1.

[0065] Table 1 Materials, reaction conditions and result data of Examples A1-A10 and Comparative Example 1

[0066]

[0067]

[0068] The results in Table 1 show that the target product can be obtained with high conversion rate by using organic carboxylic acids such as acetic acid, propionic acid, benzoic acid, lactic acid, etc. The condensation can be effectively carried out at 50-80°C (preferably 50-75°C or 50-70°C).

[0069] In a second aspect, the present invention further provides a method for synthesizing diafenthiuron, the method comprising: in the presence of an organic base, bringing the compound represented by formula (I) (4-phenoxy-2,6-diisopropylaniline) into first contact with the compound represented by formula (II) (tert-butyl isothiocyanate) to produce a condensation reaction to prepare diafenthiuron. Some embodiments are shown in Examples B1 to B10.

[0070]

[0071] Example B1

[0072] (1) 4-phenoxy-2,6-diisopropylaniline (13.5 g, 0.05 mol) and tert-butyl isothiocyanate (23.0 g, 0.20 mol) were added to a 150 mL single-necked round-bottom flask, and N-methylimidazole (8.21 g, 0.1 mol) was added. The temperature was raised to 50° C. and stirred for condensation reaction for 15 h. HPLC analysis showed that the conversion rate of 4-phenoxy-2,6-diisopropylaniline was 98% and the selectivity was 99% (butyl ether urea was the target product and 4-phenoxy-2,6-diisopropylphenyl isothiocyanate was the by-product).

[0073] (2) Tert-butyl isothiocyanate was recovered by vacuum distillation at 60°C, and the residual solid was washed with 60 mL of isopropanol and 60 mL of water, filtered, and vacuum dried at 60°C to constant weight to obtain 17.1 g of off-white solid with a yield of 89%.

[0074] The present invention also studies the influence of factors such as the type, amount, reaction temperature or reaction time of the organic base, as shown in Examples B2-B10 and Comparative Examples 2 to 4 in the following table. The operating steps of Examples B2-B10 and Comparative Examples 2 to 4 are the same as those of Example B1, except that the materials used (type and amount of organic base) and reaction conditions (reaction temperature or reaction time) are different. The specific differences are shown in Table 2.

[0075] Table 2 Materials, reaction conditions and result data of Examples B2-B10 and Comparative Examples 2-4

[0076]

[0077]

[0078] The results in Table 2 show that the target product can be obtained with high conversion rate by using organic bases such as N-methylimidazole, N-ethylimidazole, N-propylimidazole, DABCO, and DBU, and the condensation can be effectively carried out at 45-60°C.

[0079] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for synthesizing diafenthiuron, characterized in that: The method comprises: in the presence of an organic base, subjecting the compound represented by formula (I) to a condensation reaction with the compound represented by formula (II) to obtain diafenthiuron; 2. The synthesis method according to claim 1, characterized in that The organic base is a strong organic base; Optionally, the organic base has a pKa of 8-25 in DMSO at 25°C.

3. The synthesis method according to claim 1, characterized in that The organic base is selected from at least one of N-alkyl imidazole, aliphatic amine strong base, bicyclic amidine strong base, pyridine and substituted pyridine; Optionally, the alkyl group in the N-alkylimidazole is selected from a C1-C6 alkyl group, and is optionally at least one of a methyl group, an ethyl group, and a propyl group; Optionally, the fatty amine strong base is a C2-C14 fatty amine, optionally a C6-C14 fatty amine, optionally one or more of triethylenediamine, triethylamine, and N,N-diisopropylethylamine; Optionally, the bicyclic amidine strong base is a C2-C10 bicyclic amidine strong base, optionally 1,8-diazabicyclic [5.4.0] Undec-7-ene; Optionally, the substituent of the substituted pyridine is a C1-C5 alkyl group or a hydroxyl group.

4. The synthesis method according to claim 1, characterized in that The organic base is selected from at least one of N-methylimidazole, N-ethylimidazole, N-propylimidazole, 1,8-diazabicyclo[5.4.0]undec-7-ene, triethylenediamine, triethylamine, N,N-diisopropylethylamine, 2-hydroxypyridine, 2,6-lutidine and pyridine; wherein, Optionally, the organic base is selected from at least one of N-methylimidazole, N-ethylimidazole, N-propylimidazole, 1,8-diazabicyclo[5.4.0]undec-7-ene and triethylenediamine.

5. The synthesis method according to any one of claims 1 to 4, characterized in that: The molar ratio of the compound represented by formula (I) to the organic base is 1:(0.1-10), optionally 1:(0.2-5), optionally 1:(0.2-3), optionally 1:(1-5), optionally 1:(1-3), optionally 1:(1.5-3).

6. The synthesis method according to any one of claims 1 to 5, characterized in that: The condensation temperature is 30-100°C, optionally 40-90°C, optionally 40-80°C, optionally 40-75°C, optionally 40-60°C, optionally 45-60°C, optionally 45-55°C, optionally 45-50°C.

7. The synthesis method according to any one of claims 1 to 6, characterized in that: The reaction time of the condensation is 1-20h, optionally 5-20h, optionally 5-18h, optionally 8-18h, optionally 8-15h; Optionally, when an organic base is present, the reaction time of the condensation is 1-20 h, optionally 5-18 h, optionally 8-18 h, optionally 8-15 h.

8. The synthesis method according to any one of claims 1 to 7, characterized in that: The molar ratio of the compound represented by formula (I) to the compound represented by formula (II) is 1:(1-10), optionally 1:(2-10), optionally 1: (3-10), optionally 1:(2-8), optionally 1:(2-5), optionally 1:(3-6), optionally 1:(4-6).

9. The synthesis method according to any one of claims 1 to 8, characterized in that: The condensation reaction is carried out in the absence of a solvent; And / or, optionally, the by-product includes 4-phenoxy-2,6-diisopropylphenyl isothiocyanate.

10. The synthesis method according to any one of claims 1 to 9, characterized in that: After the condensation reaction, the target product is precipitated, washed with an organic solvent and / or water slurry, and dried to obtain diafenthiuron; Optionally, the method for precipitating the target product is: recovering the compound represented by formula (II) by vacuum distillation to precipitate the target product as a solid. Optionally, the temperature of the vacuum distillation can be 50-70°C.

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