Fluthidiazuron-containing derivative and preparation method thereof

Abstract

The invention discloses a fluorine-containing thidiazuron derivative and a preparation method thereof, the structure of the compound is as follows: # imgabs0 #, and R is 0-5 fluorine atoms at any position of a benzene ring. The preparation method comprises the following steps: taking 5-amino-1, 2, 3-thiadiazole as a raw material, and reacting with di-tert-butyl dicarbonate to obtain an amino-protected intermediate; 2, fluorinating the reaction intermediate obtained in the step 1 by using a fluorinating reagent to obtain a 4-fluoro intermediate; the preparation method comprises the following steps: adding 5-amino-4-fluoro-1, 2, 3-thiadiazole, and removing amino protection to obtain 5-amino-4-fluoro-1, 2, 3-thiadiazole; the preparation method comprises the following steps: reacting 5-amino-4-fluoro-1, 2, 3-thiadiazole with phenyl isocyanate with different fluoro groups, and filtering to obtain different fluorine-containing thidiazuron derivatives. A new chemical structure is designed and synthesized, and the structure is similar to a thidiazuron structure and has a good cotton defoliation effect; and the synthesis route is simple, the used reagent is easy to obtain, and the method has good application and development prospects.

Description

Technical Field

[0001] The invention relates to the technical field of plant growth regulators, and in particular to a fluorine-containing thiadiazole derivative and a preparation method thereof. Background Art

[0002] Thidiazuron is a new type of highly efficient plant growth regulator with extremely strong cell division activity. It can promote plant photosynthesis, improve fruit quality, and increase fruit storage resistance. When used as a defoliant in cotton planting, it can promote the natural formation of separation tissue between petioles and stems and cause leaf fall early, which is conducive to mechanical cotton harvesting and helps to improve cotton grades. However, when using thiazuron, there is no obvious defoliation effect when the daily minimum temperature is below 12°C, which means that thiazuron should not be used too late. If a product that can defoliate at low temperatures can be found, the application time of the defoliant can be postponed, so that more cotton bolls can be opened and cotton yields can be increased.

[0003] The invention aims to design and synthesize new fluorine-containing thiadiazole derivatives, study their properties, and contribute to the development of new cotton defoliants to increase cotton yield and quality. Summary of the invention

[0004] The invention provides a fluorine-containing thiadipyridinium derivative and a preparation method thereof. The fluorine-containing thiadipyridinium derivative of the invention is the first to report the compound structure, and provides a new idea for the development of a cotton defoliant.

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

[0006] According to the principle of electron isostericity, the present invention fluorinated the existing commercial thiadipyrone, and designed and synthesized a series of fluorine-containing thiadipyrone derivatives, the structures of which are as follows:

[0007]

[0008] Wherein, R is a benzene ring containing 0 to 5 fluorine atoms at any position.

[0009] A method for preparing a fluorine-containing thiadipyridinium derivative, the synthesis route of the fluorine-containing thiadipyridinium derivative is as follows:

[0010]

[0011] The preparation method of the fluorine-containing thiadiazole derivative comprises the following steps:

[0012] Step 1, using 5-amino-1,2,3-thiadiazole as a raw material, reacting with di-tert-butyl dicarbonate to obtain an amino-protected intermediate;

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

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

[0015] Step 4, 5-amino-4-fluoro-1,2,3-thiadiazole is reacted with different fluorinated phenyl isocyanates, and filtered to obtain different fluorine-containing thiadiazole derivatives.

[0016] Wherein, in step 1, the molar ratio of 5-amino-1,2,3-thiadiazole to di-tert-butyl dicarbonate is 1:1 to 1.5.

[0017] Wherein, in step 2, the fluorination reagents used include Selectfluor, Accufluor, NFSI, and AgF2 reagents, and the molar ratio of the amino-protected intermediate to the fluorination reagent is 1:1.5-3.

[0018] Wherein, in step 2, the solvent used is tetrahydrofuran, acetonitrile, DMF, acetone or dichloromethane.

[0019] Wherein, in step 2, the reaction temperature is between 25°C and 80°C, and the reaction time is between 2 and 8 hours.

[0020] Wherein, in step 3, the amino protection removal reagent used includes trimethylchlorosilane, hydrochloric acid, sulfuric acid, nitric acid, hydrobromic acid, and trifluoroacetic acid.

[0021] Wherein, in step 4, the different fluorinated phenyl isocyanates 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] Wherein, in step 4, the molar ratio of 5-amino-4-fluoro-1,2,3-thiadiazole to different fluorinated phenyl isocyanate isocyanates is 1:1.01-1.2.

[0023] Wherein, in step 4, the reaction solvent is dichloromethane, tetrahydrofuran, acetonitrile or DMF.

[0024] Wherein, in step 4, the reaction temperature is 25°C to 50°C, and the reaction time is 1 to 24 hours.

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

[0026] The invention designs and synthesizes a new type of chemical structure, which is similar to the structure of thidiazuron and has good cotton defoliation effect. In addition, the synthesis route is simple, the reagents used are easily available, and the invention has good application and development prospects. DETAILED DESCRIPTION

[0027] The following embodiments are provided for a better understanding of the present invention, but are not limited to the best mode of implementation, and do not limit the content and protection scope of the present invention. Any product identical or similar to the present invention obtained under the inspiration of the present invention or by combining the features of the present invention with other prior arts shall fall within the protection scope of the present invention.

[0028] Example 1

[0029] Step 1: Synthesis of 1-(4-fluoro-1,2,3-thiadiazol-5-yl)-3-phenylurea (R=H)

[0030] Weigh 15 g (150 mmol) of 5-amino-1,2,3-thiadiazole into a 250 ml round-bottom flask, add 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. The reaction mixture is stirred at 30°C for 2 h, then concentrated, and the residue is purified by silica gel chromatography to obtain 18.5 g (92 mmol) of tert-butyl N-(thiadiazole-5-yl)carbamate as a white solid, 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.

[0031] Step 2: Synthesis of tert-butyl N-(4-fluoro-thiadiazole-5-yl)carbamate

[0032] Weigh 10g (50mmol) of tert-butyl N-(thiadiazole-5-yl)carbamate, add 100ml of anhydrous acetonitrile, 35g (100mmol) of fluorination reagent Selectfluor, replace with nitrogen 3 times, heat to 60°C for 4h, after the reaction, concentrate the reaction solution, add 150ml of ethyl acetate to dissolve, add 150ml of water to extract, extract the aqueous phase with 150ml of ethyl acetate twice, combine the organic phases, add anhydrous sodium sulfate to dry. Filter and evaporate the organic phase, purify by silica gel chromatography to obtain 3.5g (16mmol) of tert-butyl N-(4-fluoro-thiadiazole-5-yl)carbamate as a white solid, with a yield of 31.8%. 1HNMR (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.

[0033] Step 3: Synthesis of 4-fluoro-1,2,3-thiadiazole

[0034] Weigh 3 g (13.7 mmol) of tert-butyl N-(4-fluoro-thiadiazole-5-yl)carbamate, add 30 ml of trifluoroethanol and 2 ml (15.7 mmol) of trimethylsilyl chloride, stir at 25 °C for 1 h, monitor the disappearance of the reaction raw materials by TLC, evaporate the solvent, and purify by silica gel chromatography to obtain 1.4 g (11.76 mmol) of 4-fluoro-1,2,3-thiadiazole in 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.

[0035] Step 4: Synthesis of 1-(4-fluoro-1,2,3-thiadiazol-5-yl)-3-phenylurea

[0036] Weigh 2g (16.8mmol) of 4-fluoro-1,2,3-thiadiazole, add 20ml of THF to dissolve, replace with nitrogen and seal. Weigh 2.1g (17.65mmol) of phenyl isocyanate, dilute with 20ml of THF, slowly add to the reaction bottle with a syringe, replace with nitrogen 3 times, stir at 25℃ for 1h, filter the precipitated solid, wash with THF and dry to obtain 2g (8.4mmol) of 1-(4-fluoro-1,2,3-thiadiazole-5-yl)-3-phenylurea, with a yield of 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.

[0037] The results of different reaction conditions in step 1 are shown in Table 1.

[0038] Table 1 Different reaction conditions and reaction results of step 1

[0039] Reaction conditions 1 Reaction Condition 2 Reaction conditions 3 Reaction Conditions 4 Reaction Conditions 5 5-Amino-1,2,3-thiadiazole dosage (mmol) 150 150 150 150 150 Di-tert-butyl dicarbonate dosage (mmol) 180 150 225 195 165 Dichloromethane dosage (ml) 150 150 150 150 150 Triethylamine dosage (mmol) 300 300 300 300 300 4-Dimethylaminopyridine dosage 15 15 15 15 15 Temperature(℃) 30 30 30 30 30 Time (h) 2 2 2 2 2 Yield (%) 62 58 66 63 60

[0040] The results of different reaction conditions in step 2 are shown in Table 2.

[0041] Table 2 Different reaction conditions and reaction results of step 2

[0042]

[0043] The results of different reaction conditions in step 3 are shown in Table 3.

[0044] Table 3 Different reaction conditions and reaction results of step 3

[0045]

[0046]

[0047] The results of different reaction conditions in step 4 are shown in Table 4.

[0048] Table 4 Different reaction conditions and reaction results of step 4

[0049]

[0050] The operations of each embodiment (2-11) are basically the same as those of embodiment 1, and the differences are shown in Table 5 below.

[0051] Table 5 Different reaction conditions and reaction results of Examples 2-11

[0052]

[0053]

[0054] Application Examples

[0055] The defoliation effect of the fluorinated thidiazuron product obtained in Examples 1-11 was compared with that of the currently commercially available thidiazuron.

[0056] The defoliation test was conducted in Henan Modern Agricultural Development Base in 2024. The local temperature was about 10°C. 12 plots were randomly divided, each plot was 3 meters long and 2 meters wide, and Example 1, Example 2, Example 3, Example 4, Example 5, Example 6, Example 7, Example 8, Example 9, Example 10, Example 11 and commercially available thidiazuron were set. Examples 1-11 were calculated based on 20g / mu of fluorinated thidiazuron derivatives. Spray evenly on the cotton leaves, and record the results as shown in Table 6:

[0057] Table 6 Fluorinated Thidiazuron Product Application Test Results

[0058]

[0059]

[0060] Among them, the commercially available sample is a 50% thidiazuron suspension, and the dosage is: 35-40 grams per mu. Per mu, 30-40 kilograms of this product is diluted with water and sprayed on the stems and leaves of the entire field.

[0061] It can be seen from the above data that the fluorinated thidiazuron derivatives prepared in the present invention have good defoliation effects.

[0062] Finally, it should be noted that the above is only 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 aforementioned embodiments, those skilled in the art can still modify the technical solutions described in the aforementioned embodiments or replace some of the technical features therein with equivalents. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A fluorine-containing thiadiazole derivative, characterized in that: The structure of this type of compound is as follows: Wherein, R is a benzene ring containing 0 to 5 fluorine atoms at any position.

2. A method for preparing the fluorine-containing thiadiazole derivative according to claim 1, characterized in that The following steps are involved: Step 1, using 5-amino-1,2,3-thiadiazole as a raw material, reacting with di-tert-butyl dicarbonate to obtain an amino-protected intermediate; Step 2, fluorinating the reaction intermediate obtained in step 1 with a fluorinating agent to obtain a 4-fluoro intermediate; Step 3, removing the amino protection to obtain 5-amino-4-fluoro-1,2,3-thiadiazole; Step 4, 5-amino-4-fluoro-1,2,3-thiadiazole is reacted with different fluorinated phenyl isocyanates, and filtered to obtain different fluorine-containing thiadiazole derivatives.

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

5.

4. The method for preparing a fluorine-containing thiadiazole derivative according to claim 2, characterized in that: In the step 2, the fluorination reagents used include Selectfluor, Accufluor, NFSI, and AgF2 reagents, and the molar ratio of the amino-protected intermediate to the fluorination reagent is 1:1.5-3.

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

6. The method for preparing a fluorine-containing thiadiazole derivative according to claim 2, characterized in that: In step 2, the reaction temperature is between 25°C and 80°C, and the reaction time is between 2 and 8 hours.

7. The method for preparing a fluorine-containing thiadiazole derivative according to claim 2, characterized in that: In step 3, the amino-removing protecting agent used includes trimethylsilyl chloride, hydrochloric acid, sulfuric acid, nitric acid, hydrobromic acid, and trifluoroacetic acid.

8. The method for preparing a fluorine-containing thiadiazole derivative according to claim 2, characterized in that: In step 4, the different fluorinated phenyl isocyanates 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.

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

2.

10. The method for preparing a fluorine-containing thiadiazole derivative according to claim 2, characterized in that: In step 4, the reaction solvent is dichloromethane, tetrahydrofuran, acetonitrile or DMF.

11. The method for preparing a fluorine-containing thiadiazole derivative according to claim 2, characterized in that: In step 4, the reaction temperature is 25°C to 50°C, and the reaction time is 1 to 24 hours.

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