CN103554026B - One group of 3-trifluoromethyl-4-formyl pyrazole compound - Google Patents

Abstract

The invention provides a group of 3-trifluoromethyl-4-formyl pyrazole compounds, the general formula of which is Wherein, X is NH, O or S, and the R group is selected from phenyl derivatives, naphthyl derivatives or heterocyclic derivatives; the present invention discloses the structures of these compounds and their control effects on agricultural diseases, and also discloses Use of these compounds as fungicides.

Description

A group of 3-trifluoromethyl-4-formylpyrazole compounds

technical field

The invention belongs to the field of pesticides, and the technical scheme relates to a group of 3-trifluoromethyl-4-formyl pyrazole compounds, in particular to a group of 3-trifluoromethyl-4-formyl pyrazole derivatives and their preparation methods and Fungicide application with it as active ingredient.

Background technique

Pyrazole compounds have high biological activity, and the application of these compounds as pesticides is attracting more and more attention. For example, Tebufenpyrad developed by Mitsubishi Chemical Co., Ltd. and Fenzafen developed by Nippon Agricultural Chemicals Co., Ltd. are both high-efficiency and broad-spectrum rapid acaricides, while the systemic fungicide furamet developed by Sumitomo Corporation of Japan and Mitsui Penthiopyrad developed by a chemical company has been used as an excellent agricultural fungicide. We have conducted in-depth research and analysis on the structure of pyrazole compounds. According to the principle of bioelectric isosterism, trifluoromethyl was introduced into the pyrazole ring, and 1-methyl-3-trifluoromethyl-4-pyrazole carboxylic acid chloride As the parent, a series of 3-trifluoromethyl-4-formylpyrazole compounds were synthesized by reacting with different nucleophilic reagents, and their bactericidal activity was determined.

Contents of the invention

The object of the present invention is to provide a group of 3-trifluoromethyl-4-formyl pyrazole compounds, the structural formula is as shown in formula I:

Wherein, X is NH, O or S, and the R group is selected from phenyl derivatives, naphthyl derivatives or heterocyclic derivatives.

Specifically, the compound shown in formula I is any one in Table 1.

Table 1 3-trifluoromethyl-4-formylpyrazole compound provided by the present invention

Another object of the present invention is to provide the preparation method of said compound, as follows:

Reaction equation:

It comprises the following steps: adding the inert solvent solution of 1-methyl- ₃ -trifluoromethyl-4-pyrazolecarbonyl chloride dropwise into the inert solvent solution of RXH and K2CO3 at low temperature ( ₀ ±5°C), After the dropwise addition, the mixture was raised to room temperature (25±5° C.) for reaction. After the reaction was completed, the reaction solvent was removed by suction filtration, and the compound was obtained after purification by recrystallization.

Specifically, the RXH is selected from any one corresponding to the compound number in Table 2.

Table 2 RXH required for the preparation of 3-trifluoromethyl-4-formylpyrazole compounds of the present invention

Specifically, the molar mass ratio of 1-methyl-3-trifluoromethyl-4-pyrazolecarbonyl chloride, RXH and K ₂ CO ₃ is 1:1:1.

Specifically, the inert solvent is acetonitrile, chloroform or toluene.

Another object of the present invention is to provide said 3-trifluoromethyl-4-formylpyrazole compound for use as an agricultural fungicide.

The beneficial effects of the present invention are: the 3-trifluoromethyl-4-formylpyrazole compound of the present invention can be used to prevent and treat agricultural diseases, and some compounds have the activity of inhibiting the growth of pathogenic bacteria, and can achieve good results.

The use of the 3-trifluoromethyl-4-formylpyrazole compound provided by the invention for preventing and controlling agricultural diseases is one of the important features of the invention.

The "three wastes" generated in the preparation process of the new compound of the invention are less, easy to handle, and more environmentally friendly when used as fungicides and pesticides.

detailed description

The present invention specifically illustrates the preparation and biological activity of 3-trifluoromethyl-4-formylpyrazole compounds through specific preparation and biological activity measurement examples. The examples are only used to specifically illustrate the present invention and not limit the present invention. invention.

The experimental methods used in the following examples are conventional methods unless otherwise specified.

The materials and reagents used in the following examples can be obtained from commercial sources unless otherwise specified.

Preparation of Example 1 Compound Q120209

Add 0.01 mol of anhydrous K ₂ CO ₃ powder, 0.01 mol of 3-methylaniline, and 30 ml of acetonitrile into a 100 ml three-necked flask equipped with a thermometer and a stirrer, and slowly add 0.01 mol of A solution prepared by dissolving 1-methyl-3-trifluoromethyl-4-pyrazolecarbonyl chloride in 20 ml of acetonitrile was added dropwise, and the reaction was continued with stirring at room temperature for 10 hours. The reaction mixture was filtered under reduced pressure, and the resulting filtrate was precipitated under reduced pressure to obtain the crude compound Q120209. The crude compound Q120209 was recrystallized with ethanol-toluene (volume ratio 1:1), and the white flaky crystal compound Q120209 was obtained. The yield was 64.2 %.

The preparation of other 17 kinds of compounds in embodiment 2～18 table 1

The specific operation is shown in Table 3.

Table 3 Embodiment 2～18 concrete operation

Example 19 Determination of Physicochemical Parameters and Chemical Structure Identification of Compounds Prepared in Examples 1-18

The melting points, ¹ H-NMR and IR of the compounds prepared in Examples 1-18 were measured, and their chemical structural formulas and physical and chemical parameters are shown in Table 4, Table 5 and Table 6.

Table 4 Physicochemical properties and yields of 3-trifluoromethyl-4-formylpyrazole compounds prepared in Examples 1-18

3-trifluoromethyl-4-formylpyrazole compound ¹ H-NMR data prepared by Table 5 Example 1-18

3-trifluoromethyl-4 formylpyrazole compound infrared spectrum data prepared by table 6 embodiment 1-18

Numbering Infrared spectrum (characteristic absorption peak) data (IR)/cm ^-1 Q120209 IR(KBr) v: 3489, 3411, 3174, 1652, 1611, 1557, 1486, 1324, 1217, 1138 Q120210 IR (KBr) v: 3224, 1644, 1557, 1482, 1395, 1308, 1270, 1179 Q120510 IR(KBr) v: 3299, 3162, 3100, 1669, 1582, 1523, 1494, 1461, 1387, 13048 --> Q120305 IR(KBr) v: 3485, 3382, 3278, 1656, 1598, 1494, 1329, 1250, 1175, 1146 Q120825 IR(KBr) v: 3245, 1652, 1565, 1507, 1441, 1316, 1217, 1183

Q120915 IR(KBr) v: 3506, 3120, 3058, 1656, 1590, 1540, 1474, 1416, 1321, 1146 Q120627 IR(KBr) v: 3290, 3195, 3133, 1656, 1606, 1548, 1519, 1407, 1324, 1175 Q120827 IR(KBr) v: 3494, 3373, 3261, 1664, 1602, 1561, 1329, 1300, 1188 Q130304 IR (KBr) v: 2963, 1652, 1565, 1432, 1337, 1175, 1134, 1059, 839, 777, 711 Q130305 IR (KBr) v: 3241, 1652, 1557, 1519, 1432, 1329, 1300, 1208, 1146, 1051, 827, 752 Q130306 IR (KBr) v: 3290, 1660, 1561, 1523, 1436, 1300, 1134, 1059, 856, 823, 711, 648 Q130307 IR (KBr) v: 2958, 1785, 1640, 1565, 1424, 1333, 1291, 1146, 1047, 847, 781, 706 Q130310 IR(KBr) v: 3456, 3054, 2963, 1694, 1627, 1557, 1424, 1341, 1308, 1171, 1129 Q130311 IR(KBr) v: 3456, 3070, 2963, 1694, 1627, 1557, 1424, 1341, 1308, 1183, 885, 711 Q130314 IR (KBr) v: 3452, 1677, 1627, 1557, 1420, 1275, 1138, 1088, 1017, 868, 764 Q130317 IR (KBr) v: 3452, 1635, 1561, 1438, 1338, 1134, 872, 781, 732, 623 Q130319 IR(KBr) v: 3170, 3116, 3054, 1689, 1557, 1436, 1316, 1175, 1134, 1059, 1005, 872 Q130320 IR (KBr) v: 1627, 1553, 1436, 1329, 1142, 839, 781, 711, 619, 516

As can be seen from Table 5 and Table 6, the ¹ H-NMR of the 3-trifluoromethyl-4-formylpyrazole compound prepared in Examples 1-18 shows that the chemical shift corresponding to its structure and the number of H are consistent with its structure, The corresponding skeleton absorption peak appears in IR.

Example 20 Determination of antibacterial activity of 3-trifluoromethyl-4-formylpyrazole compounds prepared in Examples 1-18 to seven common representative disease pathogens

(1) Preparation of PDA medium: Peel and cut 200g of potatoes into pieces, add 1000mL of distilled water, and boil for 10-20min. Filter with gauze, add distilled water to 1000mL. Add 20g of glucose and 17g of agar, heat to melt, subpackage, autoclave for 2h, and set aside.

(2) Cultivation of pathogenic fungi: Use an inoculation needle to pick a small amount of mycelia of pathogenic fungi on the PDA medium, place them in a constant temperature incubator at 25°C and cultivate them for 2-4 days, and wait for the mycelia to grow well.

(3) Determination method: the mycelia growth rate method (the size of the colony diameter within a certain period of time) was used to measure the antibacterial activity of the compound. Accurately weigh 5 mg of the target compound in a centrifuge tube, dissolve it with an appropriate amount of acetone, then add the calculated amount of aqueous solution containing 1% Tween 20 emulsifier, and dilute it into a 1000 mg/L liquid medicine. Take 1mL of the drug solution and add it into 9mL of culture medium and shake well to prepare a 100mg/L drug-containing medium, and pour it evenly into a petri dish. At the same time, a petri dish containing the same amount of acetone and Tween 20 emulsifier culture medium without the target compound of the test was added as a blank control. Use a sterilized hole puncher (diameter 4mm) to grow well, without pollution, and get the bacteria cake at the edge of the colony with uniform growth, insert the center of the medicated medium under aseptic conditions (each culture dish is inoculated with a bacteria cake), Cover the dish with the lid facing down, and repeat 3 times for each treatment. Place the culture medium in a constant temperature incubator at 25°C for cultivation. After the diameter of the colony in the control dish expands to 4-5cm, use the cross method to measure the expansion diameter of the bacterial cakes of each treatment, calculate the average value, and calculate the relative antibacterial effect by comparing with the blank control Rate.

(4) Calculation of antibacterial rate:

Colony growth diameter (mm) = colony measurement diameter (mm) - bacterial cake diameter (mm)

Relative inhibition rate (%) = [control colony growth diameter (mm) - colony growth diameter on drug-containing medium (mm)] / control colony growth diameter (mm) × 100

According to the method described above, the bacteriostasis effect of the 3-trifluoromethyl-4-formylpyrazole compound prepared in Example 1-18 on seven common representative disease pathogens is determined, and the results are shown in Table 7 (the data in the table are Inhibitory percentage of each compound on the growth of pathogenic bacteria at 100 mg/L).

Among them, azoxystrobin was the control pesticide.

The bactericidal activity of the 3-trifluoromethyl-4-formylpyrazole compound prepared by Table 7 Examples 1-18

From the data in Table 7, it can be seen that the compounds prepared in Examples 1-18 have different degrees of antibacterial activity against most of the seven selected pathogenic bacteria at a concentration of 100 mg/L, and the antibacterial rates of Q120627 pear black spot bacteria were respectively The antibacterial rate of Q130307 to apple rot pathogen reached 91.70%, and the antibacterial rate of Q130314 to tomato early blight reached 94.70%. The antibacterial rate was higher than or close to that of the control pesticide azoxystrobin.

Claims (8)

1. one group of 3-trifluoromethyl-4-formyl pyrazole compound, structural formula is such as formula shown in I:

Wherein, X is NH, O or S, and R group is selected from phenyl derivatives, naphthyl derivatives or heterocyclic radical derivative, described compound be selected from following table any one:

2. the preparation method of compound described in claim 1, comprises the following steps: at 0 ± 5 DEG C, the acetonitrile of 1-methyl-3-trifluoromethyl-4-pyrazol formyl chloride or chloroform or toluene solution are added dropwise to RXH and K ₂cO ₃acetonitrile or chloroform or toluene solution in, after dropwising, rise to 25 ± 5 DEG C of reactions, after completion of the reaction suction filtration, remove reaction solvent, after recrystallization purifying, namely obtain described compound, described RXH is selected from any one corresponding with compound number in following table:

3. preparation method according to claim 2, is characterized in that: described 1-methyl-3-trifluoromethyl-4-pyrazol formyl chloride, RXH and K ₂cO ₃molar mass ratio be 1: 1: 1.

4. the application of 3-trifluoromethyl-4-formyl pyrazole compound according to claim 1 in control farm crop agricultural disease.

5. 3-trifluoromethyl-4-formyl pyrazole compound according to claim 1 is in the application suppressing growth of pathogenic bacteria or kill in pathogenic bacteria; The microbial disease of wherein said cause of disease does not comprise the disease of human body or animal body.

6. 3-trifluoromethyl-4-formyl pyrazole compound according to claim 1 is preparing the application suppressing growth of pathogenic bacteria or kill in pathogenic bacteria medicine; The microbial disease of wherein said cause of disease does not comprise the disease of human body or animal body.

7. an agricultural composition, its comprise 0.1 ~ 99.9 % by weight the compound described in claim 1 and Pesticide Science on acceptable carrier and/or vehicle.

8. the purposes of agricultural composition according to claim 7, is characterized in that: as the application in disinfectant use in agriculture.