A fluorine-containing thidiazuron derivative and a preparation method thereof

Abstract

The application discloses a kind of fluorine-containing thidiazuron derivatives and preparation method thereof, the structure of this kind of compound is as follows: wherein, R is the benzene ring any position containing 0-5 fluorine atom.Preparation method includes the following steps: with 5-amino-1,2,3-thiadiazole as raw material, with di-tert-butyl dicarbonate reaction to obtain amino-protected intermediate;With fluorination reagent to the reaction intermediate obtained in step one is fluorinated, obtain 4-fluorinated intermediate;Remove amino protection, obtain 5-amino-4-fluoro-1,2,3-thiadiazole;5-amino-4-fluoro-1,2,3-thiadiazole and different fluorinated phenyl isocyanate reaction, filtration to obtain different fluorine-containing thidiazuron derivatives.The application designs and synthesizes a kind of new chemical structure, these structures are similar to thidiazuron structure, all have good cotton defoliation effect;And synthesis route is simple, the reagent used is easy to obtain, has good application and development prospect.

Description

Technical Field

[0001] This invention relates to the field of plant growth regulator technology, and in particular to a fluorinated thiabendazole derivative and its preparation method. Background Technology

[0002] Thiabenzochrome is a novel and highly effective plant growth regulator with strong cell division activity. It promotes photosynthesis, improves fruit quality, and increases fruit storage life. In cotton cultivation, it is used as a defoliant to induce early and natural leaf drop due to the separation of the petiole from the stem, which is beneficial for mechanical harvesting and helps improve cotton grade. However, thiabenzochrome has no significant defoliant effect when the daily minimum temperature is below 12℃, meaning its application cannot be delayed. If a product that can also defoliate at low temperatures can be found, the application time can be postponed, allowing more cotton bolls to open and increasing cotton yield.

[0003] The purpose of this invention is to design and synthesize new fluorinated thiabendazole derivatives, study their properties, and contribute to the development of new cotton defoliants to increase cotton yield and quality. Summary of the Invention

[0004] This invention provides a fluorinated thiabendazole derivative and its preparation method. The fluorinated thiabendazole derivative of this invention is the first reported compound structure, providing a new approach for the development of cotton defoliants.

[0005] To achieve the above-mentioned objectives, the technical solution of the present invention is as follows:

[0006] Based on the principle of electron isosterism, this invention fluorinated existing commercial thiazolinone to design and synthesize a series of fluorinated thiazolinone derivatives. The structures of these compounds are as follows:

[0007] ;

[0008] Where R represents the presence of 0 to 5 fluorine atoms at any position on the benzene ring.

[0009] A method for preparing a fluorinated thiazuron derivative, the synthetic route of which is shown in the figure below:

[0010]

[0011] The preparation method of fluorinated thiabendazole derivatives includes the following steps:

[0012] Step 1: Using 5-amino-1,2,3-thiadiazole as a raw material, react with ditert-butyl dicarbonate to obtain an amino-protected intermediate;

[0013] Step 2: Fluorinate the reaction intermediate obtained in Step 1 with a fluorinating agent to obtain a 4-fluoro intermediate;

[0014] Step 3: Remove amino protection to obtain 5-amino-4-fluoro-1,2,3-thiadiazole;

[0015] Step four: 5-amino-4-fluoro-1,2,3-thiadiazole is reacted with phenyl isocyanates of different fluorinations, and the mixture is filtered to obtain different fluorinated thiabendazole derivatives.

[0016] In step one, the molar ratio of 5-amino-1,2,3-thiadiazole to ditert-butyl dicarbonate is 1:1 to 1.5.

[0017] In step two, the fluorinating reagents used include Selectfluor, Accufluor, NFSI, and AgF2 reagents, and the molar ratio of the amino-protected intermediate to the fluorinating reagent is 1:1.5~3.

[0018] In step two, the solvent used is tetrahydrofuran, acetonitrile, DMF, acetone, or dichloromethane.

[0019] In step two, the reaction temperature is between 25 ℃ and 80 ℃, and the reaction time is between 2 and 8 h.

[0020] In step three, the deamination reagents used include trimethylchlorosilane, hydrochloric acid, sulfuric acid, nitric acid, hydrobromic acid, and trifluoroacetic acid.

[0021] In step four, the phenyl isocyanates with different fluorinations include phenyl isocyanate, 2-fluorophenyl isocyanate, 3-fluorophenyl isocyanate, 4-fluorophenyl isocyanate, 2,3-difluorophenyl isocyanate, 2,4-difluorophenyl isocyanate, 3,4-difluorophenyl isocyanate, 2,5-difluorophenyl isocyanate, 2,6-difluorophenyl isocyanate, 2,3,4-trifluorophenyl isocyanate, 2,3,5-trifluorophenyl isocyanate, and 3,4,5-trifluorophenyl isocyanate.

[0022] In step four, the molar ratio of 5-amino-4-fluoro-1,2,3-thiadiazole to phenyl isocyanates with different fluorination is 1:1.01~1.2.

[0023] In step four, the reaction solvent is dichloromethane, tetrahydrofuran, acetonitrile, or DMF.

[0024] In step four, the reaction temperature is 25℃~50℃ and the reaction time is 1~24h.

[0025] Compared with the prior art, the present invention has the following beneficial technical effects:

[0026] This invention designs and synthesizes a new class of chemical structures similar to thiamethoxam, both exhibiting good defoliation effects in cotton. Furthermore, the synthetic route is simple, the reagents used are readily available, and it shows great promise for application and development. Detailed Implementation

[0027] The following embodiments are provided to better understand the present invention and are not limited to the preferred embodiments described herein. They do not constitute a limitation on the content and scope of protection of the present invention. Any product that is the same as or similar to the present invention, derived under the guidance of the present invention or by combining the features of the present invention with other prior art, falls within the scope of protection of the present invention. Example 1

[0028] Step 1: Synthesis of 1-(4-fluoro-1,2,3-thiadiazol-5-yl)-3-phenylurea (R=H)

[0029] 15 g (150 mmol) of 5-amino-1,2,3-thiadiazole was weighed and added to a 250 mL round-bottom flask. Then, 150 mL of dichloromethane, 42.5 mL (180 mmol) of di-tert-butyl dicarbonate, 42.5 mL (300 mmol) of triethylamine, and 1.8 g (15 mmol) of 4-dimethylaminopyridine were added. The reaction mixture was stirred at 30 °C for 2 h, then concentrated. The residue was purified by silica gel chromatography to give 18.5 g (92 mmol) of white solid N-(thiadiazole-5-yl)carbamate tert-butyl, with a yield of 62%. 1 H NMR (DMSO, 400MHz) δ: 11.73 (s, 1H), 8.42 (s, 1H), 1.50 (s, 9H). 13 C NMRδ: 153.71, 153.19, 133.96, 82.33, 27.72.

[0030] Step 2: Synthesis of N-(4-fluoro-thiadiazol-5-yl)carbamate tert-butyl ester

[0031] 10 g (50 mmol) of N-(thiadiazol-5-yl)carbamate tert-butyl ester was weighed and added to 100 mL of anhydrous acetonitrile and 35 g (100 mmol) of Selectfluor fluorination reagent. The mixture was purged with nitrogen three times and heated to 60 °C for 4 h. After the reaction was completed, the reaction solution was concentrated, dissolved in 150 mL of ethyl acetate, and extracted with 150 mL of water. The aqueous phase was extracted twice with 150 mL of ethyl acetate. The organic phases were combined and dried over anhydrous sodium sulfate. The organic phase was filtered and evaporated to dryness. The solution was purified by silica gel chromatography to obtain 3.5 g (16 mmol) of white solid N-(4-fluoro-thiadiazol-5-yl)carbamate tert-butyl ester, with a yield of 31.8%. 1H NMR (CDCl3, 400MHz) δ: 7.58 (s, 1H), 1.55 (s, 9H). 13 C NMRδ: 158.65, 156.17, 151.99, 132.62, 132.41, 84.55, 27.99.

[0032] Step 3: Synthesis of 4-fluoro-1,2,3-thiadiazole

[0033] Weigh 3 g (13.7 mmol) of N-(4-fluoro-thiadiazol-5-yl)carbamate tert-butyl ester, add 30 ml of trifluoroethanol and 2 ml (15.7 mmol) of trimethylchlorosilane, stir at 25 °C for 1 h, monitor the disappearance of the starting material by TLC, evaporate the solvent to dryness, and purify by silica gel chromatography to obtain 1.4 g (11.76 mmol) of 4-fluoro-1,2,3-thiadiazole, with a yield of 85.9%. 1 H NMR (DMSO, 400MHz) δ: 7.16 (s, 2H). 13 C NMRδ: 156.73, 154.33, 146.45, 146.21.

[0034] Step 4: Synthesis of 1-(4-fluoro-1,2,3-thiadiazol-5-yl)-3-phenylurea

[0035] Weigh 2 g (16.8 mmol) of 4-fluoro-1,2,3-thiadiazole, dissolve it in 20 ml of THF, and seal the container after purging with nitrogen. Weigh 2.1 g (17.65 mmol) of phenyl isocyanate, add THF... Dilute 20 ml and slowly add to the reaction flask using a syringe. Purge with nitrogen three times, and stir under closed pressure at 25°C for 1 h. Filter the precipitated solid, wash with THF and dry to obtain 2 g (8.4 mmol) of 1-(4-fluoro-1,2,3-thiadiazol-5-yl)-3-phenylurea, yield 50%. 1 H NMR (DMSO, 400MHz) δ: 10.82 (s, 1H), 9.18 (s, 1H), 7.49 (d, 2H), 7.35 (d, 2H), 7.08 (t, 1H), 13 C NMRδ: 158.57, 156.12, 151.47, 146.45, 146.21.

[0036] The results of different reaction conditions in step one are shown in Table 1.

[0037]

[0038] The results of different reaction conditions in step two are shown in Table 2.

[0039]

[0040] The results of different reaction conditions in step three are shown in Table 3.

[0041]

[0042] The results of different reaction conditions in step four are shown in Table 4.

[0043]

[0044] Each embodiment (2-11) is basically the same as the operation of embodiment 1, and the differences are shown in Table 5 below.

[0045]

[0046] Application examples

[0047] The defoliation effects of the fluorinated thiabendazole products obtained in Examples 1-11 were compared with those of commercially available thiabendazole.

[0048] The defoliation experiment was conducted in 2024 at the Henan Modern Agricultural Development Base, where the local temperature was around 10℃. Twelve plots were randomly divided, each 3 meters long and 2 meters wide. Examples 1-11 were set up, including Example 1, Example 2, Example 3, Example 4, Example 5, Example 6, Example 7, Example 8, Example 9, Example 10, Example 11, and a commercially available thiamethoxam. Examples 1-11 were calculated based on 20 g / mu of fluorinated thiamethoxam derivative. The solution was sprayed evenly on the cotton leaves, and the results are recorded in Table 6 below.

[0049]

[0050] The commercially available sample is a 50% thiamethoxam suspension. The dosage is 35-40 grams per mu (approximately 0.067 hectares). For each mu, dilute the product with 30-40 kg of water and spray the entire field with the foliage.

[0051] As can be seen from the above data, the fluorinated thiamethoxam derivative prepared by this invention has a good defoliation effect.

[0052] Finally, it should be noted that the above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A fluorothiazolium derivative, characterized in that, The structure of this type of compound is as follows: ； Where R represents the presence of 0 to 5 fluorine atoms at any position on the benzene ring.

2. A method for preparing the fluorinated thiabendazole derivative according to claim 1, characterized in that... Includes the following steps: Step 1: Using 5-amino-1,2,3-thiadiazole as a raw material, react with ditert-butyl dicarbonate to obtain an amino-protected intermediate; Step 2: Fluorinate the reaction intermediate obtained in Step 1 with a fluorinating agent to obtain a 4-fluoro intermediate; Step 3: Remove amino protection to obtain 5-amino-4-fluoro-1,2,3-thiadiazole; Step four: 5-amino-4-fluoro-1,2,3-thiadiazole is reacted with phenyl isocyanates of different fluorinations, and the mixture is filtered to obtain different fluorinated thiabendazole derivatives.

3. The method for preparing a fluorothiazolium derivative according to claim 2, characterized in that: In step one, the molar ratio of 5-amino-1,2,3-thiadiazole to ditert-butyl dicarbonate is 1:1 to 1.

5.

4. The method for preparing a fluorothiazolium derivative according to claim 2, characterized in that: In step two, the fluorinating reagent used is selected from Selectfluor, Accufluor, NFSI, and AgF2 reagents, and the molar ratio of the amino-protected intermediate to the fluorinating reagent is 1:1.5~3.

5. The method for preparing a fluorothiazolium derivative according to claim 2, characterized in that: In step two, the solvent used is tetrahydrofuran, acetonitrile, DMF, acetone or dichloromethane.

6. The method for preparing a fluorothiazolium derivative according to claim 2, characterized in that: In step two, the reaction temperature is between 25℃ and 80℃, and the reaction time is between 2 and 8 hours.

7. The method for preparing a fluorothiazolium derivative according to claim 2, characterized in that: In step three, the deamination reagent used is selected from trimethylchlorosilane, hydrochloric acid, sulfuric acid, nitric acid, hydrobromic acid, and trifluoroacetic acid.

8. The method for preparing a fluorothiazolium derivative according to claim 2, characterized in that: In step four, the phenyl isocyanates with different fluorination are selected from phenyl isocyanates, 2-fluorophenyl isocyanates, 3-fluorophenyl isocyanates, 4-fluorophenyl isocyanates, 2,3-difluorophenyl isocyanates, 2,4-difluorophenyl isocyanates, 3,4-difluorophenyl isocyanates, 2,5-difluorophenyl isocyanates, 2,6-difluorophenyl isocyanates, 2,3,4-trifluorophenyl isocyanates, 2,3,5-trifluorophenyl isocyanates, and 3,4,5-trifluorophenyl isocyanates.

9. The method for preparing a fluorothiazolium derivative according to claim 2, characterized in that: In step four, the molar ratio of 5-amino-4-fluoro-1,2,3-thiadiazole to phenyl isocyanates with different fluorination is 1:1.01~1.

2.

10. The method for preparing a fluorothiazolium derivative according to claim 2, characterized in that: In step four, the reaction solvent is dichloromethane, tetrahydrofuran, acetonitrile, or DMF.

11. The method for preparing a fluorothiazolium derivative according to claim 2, characterized in that: In step four, the reaction temperature is 25℃~50℃ and the reaction time is 1~24h.

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