A fluorine-containing amide thiazolidine ester compound and its use

Abstract

The present invention discloses a fluorine-containing amide thiazolidine ester compound, the structure of which is shown in general formula I: In the formula, R 1 is: 4-C(CH 3 ) 3 , 2-CF 3 ; R 2 is: -CH 2 CF 3 , -CH 2 CHF 2 , -CH 2 CF 2 CHF 2 . The compound of general formula I has excellent biological activities against harmful mites and Lepidoptera pests such as Plutella xylostella in agriculture and forestry, and can be used for controlling harmful mites and pests in agriculture.

Description

[0001] TECHNICAL FIELD The present invention belongs to the field of agricultural insecticides and acaricides, and relates to a fluoroamide thiazolidine ester compound and its use.

[0002] BACKGROUND ART Chemical pesticides are the main means for controlling diseases, insects and mites in agriculture. Thiazole compounds have important applications in pesticides such as insecticides, acaricides and fungicides. Fluorine-containing pesticides relatively have the characteristics of less dosage, low toxicity and high efficacy in performance. The present invention synthesizes a fluoroamide thiazolidine ester compound. In the prior art, the general formula I compound as described in the present invention and its use as an agricultural and forestry insecticide and acaricide have not been disclosed.

[0003] SUMMARY OF THE INVENTION The purpose of the present invention is to provide an insecticide and acaricide with novel structure, high efficiency and safety, which can be used for effectively controlling common insect pests and mite pests in agriculture.

[0004] The technical solution of the present invention is as follows:

[0005] The present invention provides a fluoroamide thiazolidine ester compound, the structure of which is shown in general formula I:

[0006] In the formula, R 1 is: 4-C(CH 3 ) 3 , 2-CF 3 ; R 2 is: -CH 2 CF 3 , -CH 2 CHF 2 ,

[0007] -CH 2 CF 2 CHF 2 .

[0008] The general formula I compound of the present invention can be prepared by the following method, and the definitions of each group in the reaction formula are the same as above.

[0009]

[0010] The specific preparation methods of the general formula I compound and its intermediates can be seen in the synthesis examples of the present invention.

[0011] Table 1 lists the structures and physical properties of the general formula I compound.

[0012] Table 1 Structures and Physical Properties of Compound I

[0013] Compound <![CDATA[R 1 > <![CDATA[R 2 > Appearance <![CDATA[Ⅰ a > <![CDATA[4-C(CH 3 ) 3 > <![CDATA[-CH 2 CF 3 > White solid, m.p. 73.3 - 74.2 °C <![CDATA[Ⅰ b > <![CDATA[4-C(CH 3 ) 3 > <![CDATA[-CH 2 CHF 2 > White solid, m.p. 56.3 - 57.2 °C. <![CDATA[Ⅰ c > <![CDATA[4-C(CH 3 ) 3 > <![CDATA[-CH 2 CF 2 CHF 2 > Pale yellow viscous liquid Ⅰd <![CDATA[2-CF 3 > <![CDATA[-CH 2 CF 2 CHF 2 > Colorless oily liquid <![CDATA[Ⅰ e > <![CDATA[2-CF 3 > <![CDATA[-CH 2 CHF 2 > Colorless oily liquid

[0014] Advantages and Positive Effects of the Present Invention:

[0015] The compound of the present invention is a novel fluorinated amide thiazolidine ester compound with a completely new structure. It contains fluorine atoms and thiazolidine groups in its structure. The fluorinated group increases liposolubility and permeability, significantly improves its systemic conduction effect, and thus enhances its efficacy; the thiazole structure increases the action sites, which is beneficial to increasing efficacy and broad-spectrum property and is less affected by pest resistance. The synthetic raw materials of the compound of the present invention are easily available, the synthetic process is simple, without high temperature, high pressure and special equipment, the generation of "three wastes" in production is less, the yield is relatively high, and the production cost is low. The compound of the present invention is an azacyclic amide ester compound, with the characteristics of low toxicity to humans, livestock and beneficial organisms, easy degradation and good environmental compatibility, and has the prospect of industrialization and the potential of commercialization as a new variety of innovative insecticides and acaricides.

[0016] When the compound of formula I of the present invention and its salts are used in controlling harmful insects and mites, they can be used alone or in combination with other active substances to improve the comprehensive performance of the product.

[0017] The composition of the present invention can be applied in the form of a formulation. The compound of general formula I is dissolved or dispersed in a carrier or solvent as an active component, and an appropriate surfactant is added to formulate emulsifiable concentrates, suspension concentrates, microemulsions or wettable powders, etc.

[0018] It should be clear that within the scope defined by the claims of the present invention, various transformations and modifications can be made. Detailed implementation manners

[0019] The following synthetic examples and bioassay results can be used to further illustrate the present invention, but do not mean to limit the present invention.

[0020] Synthetic examples:

[0021] Example 1. Preparation of compound I a :

[0022] (1) Synthesis of thiazolidine-4-carboxylic acid

[0023]

[0024] In a 250 mL three-necked flask, first add 100 mL of aqueous formaldehyde solution (36%) (1.2 mol), and then add 12.1 g (0.1 mol) of L-cysteine. Stir and react at room temperature for 6 h. Stop stirring and perform suction filtration to obtain 12.4 g of white solid thiazolidine-4-carboxylic acid, with a yield of 93.2%. Collect the filtrate for continued reuse.

[0025] (2) Synthesis of p-tert-butylbenzoyl chloride

[0026]

[0027] In a 250 mL single-necked flask, first add 17.8 g (0.1 mol) of p-tert-butylbenzoic acid, then add 80 mL of toluene as the reaction solvent, and then add 13.6 g (0.115 mol) of thionyl chloride. Add a reflux condenser, stir, and heat the reaction to reflux. Under reflux conditions, react for 4 h. Monitor the reaction progress by TLC. After the reaction is complete, distill off the excess solvent and thionyl chloride under reduced pressure to obtain 19.5 g of p-tert-butylbenzoyl chloride, which is a pale yellow liquid with a yield of 96%.

[0028] (3) Synthesis of 3-(4-(tert-butyl)benzoyl)thiazolidine-4-carboxylic acid

[0029]

[0030] In a 250 mL three-necked flask, first add 13.3 g (0.1 mol) of thiazolidine-4-carboxylic acid, then add 60 mL of toluene as the reaction solvent, and then add 11 g (0.11 mol) of triethylamine as an acid-binding agent. Finally, slowly add 19.6 g (0.1 mol) of p-tert-butylbenzoyl chloride dropwise at room temperature. After the addition is complete, slowly raise the temperature to 60 °C and continue the reaction for 6 h. Monitor the reaction process by TLC. After the reaction is completed, cool down, wash the reaction solution three times (3 × 20 mL) with 60 mL of saturated sodium chloride aqueous solution, take the organic phase, dry it with anhydrous sodium sulfate, and distill off the solvent under reduced pressure to obtain 20 g of the intermediate 3-(4-(tert-butyl)benzoyl)thiazolidine-4-carboxylic acid, which is a transparent viscous liquid with a yield of 68.3%.

[0031] (4) Synthesis of compound Ⅰa

[0032]

[0033] In a 100 mL three-necked flask, first add 5.86 g (0.02 mol) of intermediate V2a1, then add 30 mL of toluene as the solvent, then add 6 g (0.06 mol) of 2,2,2-trifluoroethanol, and additionally add 0.2 g of p-toluenesulfonic acid as a catalyst. Stir and slowly raise the temperature to reflux. Under reflux conditions, react for 4 h. Monitor the reaction by TLC. After the reaction is completed, cool down to room temperature, add 30 mL of water to the reaction system, extract with ethyl acetate (3 × 30 mL), take the organic phase, wash it with saturated brine, and then dry it with anhydrous sodium sulfate. Distill off the ethyl acetate under reduced pressure to obtain the crude product, which is separated by column chromatography (V(ethyl acetate):V(petroleum ether) = 1:15) to obtain the target compound Ⅰ a , which is a white solid with a yield of 56%.

[0034] Other target compounds Ⅰ b ~Ⅰe are prepared similarly to Ⅰ a .

[0035] NMR data of the target compound:

[0036] Ⅰa: 1 H NMR (400 MHz, DMSO-d 6 ) δ (ppm): 7.49 (m, 4H, Ar-H), 5.19–5.12 (m, 1H, Thiazole-CH), 4.85 (q, J = 9.0 Hz, 2H, CH 2 ), 4.69 (s, 1H, Thiazole-CH 2 ), 4.60 (s, 1H, Thiazole-CH 2 ), 3.52 (dd, J = 11.6, 7.2 Hz, 1H, Thiazole-CH 2 ), 3.21 (dd, J = 11.9, 4.5 Hz, 1H, Thiazole-CH 2 ), 1.30 (s, 9H). 13 C NMR (126 MHz, DMSO-d 6 ) δ (ppm) 167.39, 166.83 (d, J = 27.9 Hz), 152.32, 131.21, 125.91, 124.12, 123.22, 59.24, 50.01, 33.44, 31.26, 29.71.

[0037] Ⅰb: 1 H NMR (500 MHz, Chloroform-d) δ 7.55–7.37 (m, 4H, Ar-H), 5.94 (t, J = 54.6 Hz, 1H, CHF 2 ), 5.53–5.15 (m, 1H, Thiazole-CH), 4.60 (s, 2H, Thiazole-CH 2 ), 4.34 (d, J = 13.1 Hz, 2H, CH 2 ), 3.36 (d, J = 29.5 Hz, 1H, Thiazole-CH 2 ), 3.22 (d, J = 7.0 Hz, 1H, Thiazole-CH 2 ), 1.28 (s, 9H, CH 3 ). 13 C NMR (126 MHz, DMSO-d 6 ) δ (ppm) 167.61, 152.58, 130.59, 128.22, 125.58, 123.82, 110.90, 61.50, 59.61, 49.72, 33.20, 29.45, 28.03.

[0038] Ⅰc: 1 H NMR(500MHz, DMSO-d 6 ) δ(ppm): 7.51(m, 4H, Ar-H), 6.60(t, J = 51.9Hz, 1H, CHF 2 ), 5.15(m, 1H, Thiazole-CH), 4.71(m, 4H, Thiazole-CH 2 , CH 2 ), 3.52(m, 1H, CH 2 ,), 3.23(dd, J = 11.9, 4.7Hz, 1H, CH 2 ,), 1.31(s, 9H, CH 3 ). 13 C NMR(126MHz, DMSO-d 6 ) δ(ppm) 168.59, 168.12, 153.38, 132.16, 129.07, 126.97, 125.14, 109.02, 61.05, 60.00, 51.64, 51.07, 34.47, 32.31, 30.73.

[0039] Ⅰd: 1 H NMR(500MHz, Chloroform-d) δ(ppm): 7.78(d, J = 7.9Hz, 1H, Ar-H), 7.68(d, J = 7.5Hz, 1H, Ar-H), 7.61(t, J = 7.7Hz, 2H, Ar-H), 6.08–5.87(m, 1H, CHF 2 ), 5.38(dd, J = 7.2, 4.5Hz, 1H, Thiazole-CH), 4.68(s, 2H, CH 2 ), 4.38(d, J = 8.8Hz, 1H, Thiazole-CH 2 ), 4.26(d, J = 8.9Hz, 1H, Thiazole-CH 2 ), 3.44(d, J = 7.2Hz, 1H, Thiazole-CH 2 ), 3.35(d, J = 4.5Hz, 1H, Thiazole-CH 2 ). 1313C NMR (126 MHz, Chloroform-d) δ (ppm): 167.84, 166.35, 133.53, 131.97, 129.55, 127.22, 126.81, 126.32, 123.99, 121.81, 108.75, 60.15, 59.85, 49.91, 32.66。

[0040] Ⅰe: 1 1H NMR (500 MHz, Chloroform-d) δ (ppm): 7.76 (d, J = 7.7 Hz, 1H, Ar-H), 7.67 (t, J = 7.4 Hz, 1H, Ar-H), 7.59 (t, J = 7.2 Hz, 1H, Ar-H), 7.48 (d, J = 13.1 Hz, 1H, Ar-H), 6.14–5.90 (m, 1H, CHF 2 ), 5.37 (dd, J = 7.2, 4.3 Hz, 1H, Thiazole-CH), 4.46–4.32 (m, 3H, Thiazole-CH 2 , CH 2 ), 4.25 (d, J = 8.8 Hz, 1H, Thiazole-CH 2 ), 3.44 (dd, J = 11.9, 7.2 Hz, 1H, Thiazole-CH 2 ), 3.33 (dd, J = 11.9, 4.4 Hz, 1H, Thiazole-CH 2 )。 13 13C NMR (126 MHz, Chloroform-d) δ (ppm): 168.28, 166.26, 133.60, 131.96, 129.51, 126.87, 126.32, 124.00, 121.82, 111.90, 62.84, 60.15, 49.83, 32.71。

[0041] Biological activity assay:

[0042] Example 2, Insecticidal activity test of Compound of Formula Ⅰ

[0043] Bioactivity test method against Plutella xylostella: Refer to Part 14: Leaf-dipping method in NY / T 1154.14-2008 "Guidelines for Pesticide Bioassay in the Laboratory - Insecticides" for bioactivity test. The specific method is as follows: Prepare a series of diluted solutions of the agent according to the experimental design, using 0.1% Tween-80 water as the control; Select fresh cabbage leaves, cut them into 3-cm square pieces, immerse them in the corresponding agent for 10 s and then take them out to dry naturally. Place a 9-cm diameter filter paper flat on the bottom of a 9-cm diameter petri dish, put 3rd instar larvae of Plutella xylostella of the same size, after 2 h of starvation treatment, put in the poisoned leaves; Each treatment has 3 replicates, place them under the conditions of (26±1)°C, light 16 h:8 h (L:D), after 24 h, 48 h, and 72 h of treatment, those that cannot move when touched with a writing brush are considered dead, record the number of dead insects, and calculate the mortality and corrected mortality of each treatment.

[0044] Mortality (%) = Number of dead insects / Total number of treated insects × 100

[0045] Corrected mortality (%) = (Treatment mortality - Control mortality) / (100 - Control mortality) × 100

[0046] Table 2 Test results of the bioactivity of Compound Ⅰ against Plutella xylostella

[0047]

[0048]

[0049] It can be seen from the experimental data in Table 2 that Compound Ⅰ has excellent killing activity against Plutella xylostella. Among them, Ⅰa, Ⅰd, and Ⅰe have excellent activities. When the mass concentration is 10 mg / L, the insecticidal activity is above 90%. When the mass concentration drops to 1 mg / L, it still remains above 70%.

[0050] Example 3. Acaricidal activity test of Compound Ⅰ

[0051] Bioactivity test method against Tetranychus urticae: Refer to Part 9: Spraying method in NY / T 1154.9-2008 "Guidelines for Pesticide Bioassay in the Laboratory - Insecticides" for bioactivity test. The specific method is as follows: Prepare a series of diluted solutions of the agent according to the experimental design, using 0.1% Tween-80 water as the control; Take potted pepper seedlings with consistent growth vigor, inoculate 30 adult mites of Tetranychus urticae on each pepper seedling, apply vaseline to the stem to prevent adult mites from escaping; Place them in an insect rearing room for 24 h, check the original number of insects, and then place them in the insect rearing room for cultivation. Each concentration has 3 replicates. Place them under the conditions of (26±1)°C, relative humidity 70% - 80%, and light 16 h:8 h (L:D) for normal feeding. Record the total number of insects before treatment, and record the remaining number of adult mites of Tetranychus urticae at 24 h, 48 h, and 72 h after treatment, and calculate the mortality and corrected mortality.

[0052] Table 3 Test results of the acaricidal activity of the compounds of formula Ⅰ against Tetranychus urticae

[0053]

[0054] It can be seen from the test data in Table 3 that the compound I of the present invention has excellent acaricidal activity. Among them, Ⅰa and Ⅰd have excellent activities, and when the mass concentration is 100 mg / L, the acaricidal activity against Tetranychus urticae reaches 90%.

Claims

1. A fluoroamide thiazolidine ester compound has a structure shown in general formula I: wherein R 1 is: 4-C(CH 3 ) 3 , 2-CF 3 ; R 2 is: -CH 2 CF 3 , -CH 2 CHF 2 , -CH 2 CF 2 CHF 2 。 2. Use of a fluoroamide thiazolidine ester compound according to claim 1, characterized in that the compound of general formula I is used alone or in combination with another bioactive compound to control pests and mites in agriculture and forestry.

3. An insecticidal and acaricidal composition contains the compound of general formula I according to claim 1 as an active ingredient and an agriculturally and forestry-acceptable carrier.

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