Furan type oxidized linalool ether derivative as well as preparation method and application thereof

Abstract

The invention discloses a furan type oxidized linalool ether derivative as well as a preparation method and application thereof, and the preparation method comprises the following steps: adding furan type oxidized linalool, halogenated hydrocarbon and NaH into a solvent, and reacting at 90-144 DEG C for 1-16 hours to obtain the furan type oxidized linalool ether derivative. The invention finds that the furan type linalool oxide and the prepared furan type linalool oxide ether derivative have a good inhibition effect on the growth of annual ryegrass, and have the potential of being developed into a green plant source herbicide. According to the preparation method, the reaction conditions are mild, the reaction can be carried out under normal pressure, the technological process is simple and easy to operate, raw materials are easy to obtain, and industrial production is facilitated.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthesis, and particularly relates to a furanoid linalool oxide ether derivative, a preparation method thereof and an application thereof. Background Art

[0002] Furanoid linalool oxide is an important organic compound, and its source is mainly obtained by oxidizing linalool, which is one of the rare natural products. Because of its special aroma, it is widely used in the fragrance field. However, in recent years, researchers have found that furanoid linalool oxide has good biological activity and high safety. At present, the research mainly focuses on its antibacterial activity, but there is no literature report on the herbicidal activity of furanoid linalool oxide and its derivatives.

[0003] Ethers mainly refer to a class of organic compounds containing an ether bond (-O-). Ether compounds have various biological activities such as herbicidal and antibacterial activities. For example, Huang et al. found that the benzyl ether derivatives of (3R,4R)-4,7,7-trimethyl-6-oxabicyclo[3.2.1]octane-3,4-diol have excellent herbicidal activity, which is similar to or better than that of glyphosate (Industrial Crops and Products, 2019, 129(5)). Because ether compounds have the above various biological activities, the preparation of ether compounds has always been one of the research directions of people.

[0004] In this study, a series of furanoid linalool oxide ether derivatives were designed and synthesized with the expectation of obtaining a new type of green plant-derived herbicide with strong herbicidal activity and little environmental impact. The study used furanoid linalool oxide as a raw material to synthesize a series of furanoid linalool oxide ether derivatives that have not been reported in the literature through a one-step synthesis. Summary of the Invention

[0005] The purpose of the present invention is to provide a furanoid linalool oxide ether derivative, a preparation method thereof and an application thereof. This method has the advantages of easy operation, relatively mild reaction conditions, low cost, little pollution, etc., and is easy to realize industrialization.

[0006] The present invention provides a furanoid linalool oxide ether derivative, and its structural formula is:

[0007]

[0008] Wherein, Any one of.

[0009] The present invention also provides a preparation method of a furanoid linalool oxide ether derivative, which comprises the following steps:

[0010] Furanoid linalool oxide, a halogenated hydrocarbon, and NaH are added to a solvent, and after reacting at 90 °C to 144 °C for 1 h to 16 h, a furanoid linalool oxide ether derivative is obtained.

[0011] Preferably, the halogenated hydrocarbon is RCl, and any one of the is used.

[0012] Preferably, the solvent is at least one of toluene, xylene, or mesitylene.

[0013] Preferably, the molar ratio of the furanoid linalool oxide to the halogenated hydrocarbon is 1:0.8 - 1.2.

[0014] Meanwhile, the present invention also provides an application of a furanoid linalool oxide ether derivative as an active ingredient of a herbicide.

[0015] Preferably, the application of the furanoid linalool oxide ether derivative as an active ingredient of a herbicide includes the following steps: adding annual ryegrass seeds to a solution of the furanoid linalool oxide ether derivative and culturing at 25 °C for 5 d.

[0016] Preferably, the concentration of the solution of the furanoid linalool oxide ether derivative is 0.1563 - 5 mmol / L.

[0017] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0018] 1. The furanoid linalool oxide and its ether derivatives of the present invention are natural plant-derived products, which are natural monoterpene oxygen heterocyclic derivatives, and have the characteristics of low toxicity, high safety, and environmental friendliness.

[0019] 2. The reaction conditions of the present invention are relatively mild, and the temperature is generally controlled at 90 °C to 144 °C, and the reaction can be carried out under normal pressure.

[0020] 3. The process of the present invention is simple and easy to operate, the raw materials are easy to obtain, the environmental pollution is small, and it is easy to realize industrialization. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] In order to more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the following will briefly introduce the drawings required for the description of the specific embodiments or the prior art. Obviously, the following drawings are some embodiments of the present invention. For those of ordinary skill in the art, other information can also be obtained based on these drawings without creative efforts.

[0022] Figure 1 It is the infrared spectrum (FT-IR) diagram of the reaction product of furanoid linalool oxide and benzyl chloride of the present invention;

[0023] Figure 2 High resolution mass spectrometry (HRMS) of the reaction product of furanoid linalool oxide and benzyl chloride of the present invention;

[0024] Figure 3 Of the reaction product of furanoid linalool oxide and benzyl chloride of the present invention 1 H nuclear magnetic resonance ( 1 HNMR). Detailed implementation mode

[0025] The following examples are provided to better further understand the present invention, which is not limited to the described optimal implementation mode, and does not limit the content and protection scope of the present invention. Any product that is the same as or similar to the present invention obtained by anyone under the inspiration of the present invention or by combining the features of the present invention with other prior art features falls within the protection scope of the present invention.

[0026] For those not specifying specific experimental steps or conditions in the examples, the operations or conditions of the conventional experimental steps described in the literature in this field can be followed. For the reagents or instruments not specifying the manufacturer, they are all conventional reagent products that can be obtained through commercial purchase.

[0027] The synthesis reaction formula of furanoid linalool oxide ether derivatives is as follows:

[0028]

[0029] Among them,

[0030]

[0031] Example 1

[0032] Add 20 mmol of furanoid linalool oxide (A), 24 mmol of benzyl chloride, 30 mL of mesitylene, and 1.6 g of sodium hydride (purity 60%) to a 100 mL three-necked flask, stir, and heat under reflux (144 °C) for 8 h. After the reaction is completed, the reaction solution is washed successively with distilled water, the solvent is removed by rotary evaporation, and after silica gel column chromatography and vacuum drying, 1.56 g of product (colorless oily liquid) compound B1 is obtained, with a yield of 30.0%.

[0033] The HR-MS, FT-IR and 1 H-NMR characterization data of compound B1 are as follows:

[0034] HRMS(ESI)for C 17 H 25 O2, calcd. 261.1849, found 261.1845 [M+H] +, Δ = 1.53 ppm. FT-IR (cm -1 ): 3063 (m, ν C＝C-H ); 2972, 2927, 2861 (s, ν C-H ); 1601, 1496 (m, ν C＝C ); 1454, 1362 (m, δ C-H ); 1094, 1068 (s, ν C-O-C ). 1 1H-NMR (DMSO-d6, 600 MHz) δ H 7.29 - 7.33 (5H, m, Ph-H), 5.87 - 5.99 (1H, m, 8-H), 5.15 - 5.18 (1H, m, 7-H), 4.93 - 4.98 (1H, m, 7-H), 4.47 - 4.51 (2H, m, Ph-C H 2-), 3.89 - 3.96 (1H, m, 5-H), 3.38 (s, H 2O), 2.50 - 2.51 (m, DMSO-H), 1.63 - 1.82 (4H, m, 3-H, 4-H), 1.24 (3H, d, J = 13.1 Hz, 6-H), 1.21 (3H, s, 10-H), 1.18 (3H, d, J = 6.0 Hz, 9-H).

[0035] Example 2

[0036] Add 20 mmol of furfuryl linalool oxide, 24 mmol of o-methylbenzyl chloride, 30 mL of mesitylene, and 1.6 g of sodium hydride (purity 60%) to a 100 mL three-necked flask, stir, and reflux for 8 h. After the reaction is completed, the reaction solution is washed successively with distilled water, the solvent is removed by rotary evaporation, and then subjected to silica gel column chromatography and vacuum drying to obtain 1.62 g of product (light yellow oily liquid) Compound B2, with a yield of 29.6%.

[0037] The HR-MS, FT-IR and 1 1H-NMR characterization data of Compound B2 are as follows:

[0038] HRMS (ESI) for C 18 H 26 O2Na, calcd. 297.18231, found 297.18250 [M+Na] + , Δ = 0.64 ppm. FT-IR (cm -1 ): 3071 (m, ν C＝C-H ); 2974, 2874 (s, ν C-H ); 1608 (m, ν C＝C); 1462, 1374 (m, δ C-H ); 1068 (s, ν C-O-C ). 1 1H-NMR (DMSO-d6, 600 MHz) δ H 7.13 - 7.38 (4H, m, Ph-H), 5.87 - 6.02 (1H, m, 8-H), 5.21 - 5.24 (1H, m, 7-H), 4.95 - 4.99 (1H, m, 7-H), 4.47 - 4.53 (2H, m, Ph-C H 2-), 3.93 - 4.00 (1H, m, 5-H), 3.43 (s, H 2O), 2.30 (3H, s, Ph-C H 3), 1.64 - 1.84 (4H, m, 3-H, 4-H), 1.29 (3H, d, J = 7.4 Hz, 6-H), 1.27 (3H, s, 10-H), 1.24 (3H, d, J = 3.8 Hz, 9-H).

[0039] Example 3

[0040] Add 20 mmol of furfuryl linalool, 24 mmol of p-chlorobenzyl chloride, 30 mL of mesitylene and 1.6 g of sodium hydride (purity 60%) to a 100 mL three-necked flask, stir, and reflux at heating for 8 h. After the reaction is completed, the reaction solution is washed successively with distilled water, the solvent is removed by rotary evaporation, and then subjected to silica gel column chromatography and vacuum drying to obtain 2.43 g of the product (yellow oily liquid) Compound B3, with a yield of 41.3%.

[0041] The HR-MS, FT-IR and 1 1H-NMR characterization data of Compound B3 are as follows:

[0042] HRMS (ESI) for C 17 H 23 ClO2Na, calcd. 317.12766, found 317.12788 [M+Na] + , Δ = 0.69 ppm. FT-IR (cm -1 ): 3083 (m, ν C＝C-H ); 2975, 2872 (s, ν C-H ); 1599 (m, ν C＝C ); 1486, 1373 (m, δ C-H ); 1084 (s, ν C-O-C ). 1 1H-NMR (DMSO-d6, 600 MHz) δ H7.31 - 7.40 (4H, m, Ph - H), 5.83 - 5.88 (1H, m, 8 - H), 5.13 - 5.14 (1H, m, 7 - H), 4.95 - 4.96 (1H, m, 7 - H), 4.47 - 4.51 (2H, m, Ph - C H 2 - ), 3.86 - 3.88 (1H, m, 5 - H), 3.37 (s, H 2O), 2.50 - 2.52 (m, DMSO - H), 1.60 - 1.80 (4H, m, 3 - H, 4 - H), 1.23 (3H, s, 6 - H), 1.19 (3H, s, 10 - H), 1.16 (3H, d, s, 9 - H).

[0043] Example 4

[0044] Add 20 mmol of furfuryl linalool, 24 mmol of p - fluorobenzyl chloride, 30 mL of mesitylene and 1.6 g of sodium hydride (purity 60%) to a 100 mL three - necked flask, stir, and reflux at heating for 8 h. After the reaction is completed, the reaction solution is washed successively with distilled water, the solvent is removed by rotary evaporation, and then purified by silica gel column chromatography and vacuum dried to obtain 1.72 g of product (yellow oily liquid) compound B4, with a yield of 30.9%.

[0045] The HR - MS, FT - IR and 1 1H - NMR characterization data are as follows:

[0046] HRMS(ESI) for C 17 H 23 FO2Na, 301.15720, found 301.15743 [M + Na] + , Δ = 0.73 ppm. FT - IR (cm -1 ): 3084 (m, ν C＝C-H ); 2975, 2873 (s, ν C-H ); 1607, 1513 (m, ν C＝C ); 1462, 1374 (m, δ C-H ); 1070 (s, ν C-O-C ). 1 1H - NMR (DMSO - d6, 600 MHz) δ H 7.09 - 7.34 (4H, m, Ph - H), 5.84 - 5.88 (1H, m, 8 - H), 5.14 - 5.17 (1H, m, 7 - H), 4.95 - 4.97 (1H, m, 7 - H), 4.46 - 4.50 (2H, m, Ph - C H 2 - ), 3.87 - 3.89 (1H, m, 5 - H), 3.39 (s,H 2O), 2.50 - 2.51 (m, DMSO - H), 1.59 - 1.84 (4H, m, 3 - H, 4 - H), 1.24 (3H, s, 6 - H), 1.20 (3H, s, 10 - H), 1.17 (3H, s, 9 - H).

[0047] Example 5

[0048] Add 20 mmol of furfuryl linalool, 25 mmol of 2,6 - dichlorobenzyl chloride, 30 mL of mesitylene, and 1.6 g of sodium hydride (purity 60%) to a 100 mL three - necked flask, stir, and reflux for 8 h. After the reaction is completed, the reaction solution is washed successively with distilled water, the solvent is removed by rotary evaporation, and then purified by silica gel column chromatography and vacuum dried to obtain 4.64 g of the product (yellow oily liquid) compound B5, with a yield of 70.5%.

[0049] The HR - MS, FT - IR, and 1 1H - NMR characterization data of compound B5 are as follows:

[0050] HRMS(ESI) for C 17 H 22 Cl2O2Na, calcd. 351.08865, found 351.08891 [M + Na] + , Δ = 0.74 ppm. FT - IR(cm -1 ): 3084 (m, ν C＝C-H ); 2972, 2928 (s, ν C-H ); 1583, 1564 (m, ν C＝C ); 1386, 1365 (m, δ C-H ); 1093, 1065 (s, ν C-O-C ). 1 1H - NMR(DMSO - d6, 600 MHz) δ H 7.24 - 7.29 (3H, m, Ph - H), 5.79 - 5.90 (1H, m, 8 - H), 5.14 - 5.17 (1H, m, 7 - H), 4.86 - 4.87 (1H, m, 7 - H), 4.63 - 4.64 (2H, m, Ph - C H 2 - ), 3.84 - 3.92 (1H, m, 5 - H), 3.40 (s, H 2O), 2.51 - 2.53 (m, DMSO - H), 1.57 - 1.84 (4H, m, 3 - H, 4 - H), 1.24 (3H, d, J = 3.0 Hz, 6 - H), 1.22 (3H, s, 10 - H), 1.19 (3H, d, J = 6.2 Hz, 9 - H).

[0051] Example 6

[0052] Add 20 mmol of furfuryl linalool oxide, 24 mmol of benzyl chloride, 30 mL of xylene, and 1.6 g of sodium hydride (purity 60%) to a 100 mL three-necked flask, stir, and reflux at heating for 8 h. After the reaction is completed, the reaction solution is washed successively with distilled water, the solvent is removed by rotary evaporation, and then subjected to silica gel column chromatography and vacuum drying to obtain 1.16 g of product (colorless oily liquid), and the yield is 22.3%.

[0053] Example 7

[0054] Add 20 mmol of furfuryl linalool oxide, 24 mmol of benzyl chloride, 30 mL of toluene, and 1.6 g of sodium hydride (purity 60%) to a 100 mL three-necked flask, stir, and reflux at heating for 8 h. After the reaction is completed, the reaction solution is washed successively with distilled water, the solvent is removed by rotary evaporation, and then subjected to silica gel column chromatography and vacuum drying to obtain 0.52 g of product (colorless oily liquid), and the yield is 10.0%.

[0055] Example 8

[0056] Add 20 mmol of furfuryl linalool oxide, 24 mmol of benzyl chloride, 30 mL of mesitylene, and 1.6 g of sodium hydride (purity 60%) to a 100 mL three-necked flask, stir, and react at 90 °C for 8 h. After the reaction is completed, the reaction solution is washed successively with distilled water, the solvent is removed by rotary evaporation, and then subjected to silica gel column chromatography and vacuum drying to obtain 0.32 g of product (colorless oily liquid), and the yield is 6.2%.

[0057] Example 9

[0058] Add 20 mmol of furfuryl linalool oxide, 24 mmol of benzyl chloride, 30 mL of mesitylene, and 1.6 g of sodium hydride (purity 60%) to a 100 mL three-necked flask, stir, and reflux at heating (144 °C) for 16 h. After the reaction is completed, the reaction solution is washed successively with distilled water, the solvent is removed by rotary evaporation, and then subjected to silica gel column chromatography and vacuum drying to obtain 1.52 g of product (colorless oily liquid), and the yield is 29.2%.

[0059] Application Example

[0060] Test on the herbicidal activity of furfuryl linalool oxide and ether derivatives: The petri dish seed germination method is adopted, and the tested grass seeds are annual ryegrass seeds (Barenbrug Group).

[0061] Add 1 mmol of the sample to be tested into a 10 mL beaker, dissolve it with 0.25 mL of N,N-dimethylformamide, add a drop of Tween 80, dilute it with an appropriate amount of distilled water, and transfer it to a 100 mL volumetric flask. Then dilute it to the calibration line with distilled water to obtain a solution with a concentration of 10 mmol / L, which is used as the stock solution. Using the two-fold dilution method, sequentially dilute the stock solution to 5 mmol / L, 2.5 mmol / L, 1.25 mmol / L, 0.625 mmol / L, 0.3125 mmol / L, and 0.1563 mmol / L. Add five drops of Tween 80 solution and 1.25 mL of N,N-dimethylformamide into a 500 mL volumetric flask, and dilute it to the calibration line with distilled water as the blank control solution.

[0062] Soak the annual ryegrass seeds in sterile deionized water at 25 °C for 15 h. Place a filter paper at the bottom of a petri dish (φ9 cm), attach the concentration label, and add 10 mL of the sample solution to be tested with the corresponding concentration. Add 10 mL of the blank control solution to the blank control group. Repeat each concentration 3 times. Add 10 annual ryegrass seeds to each of the above petri dishes in sequence, place them in an artificial climate chamber, and culture at 25 °C for 5 d. The experimental data is processed and analyzed using DPS software.

[0063]

[0064] In the formula:

[0065] y—the inhibition rate of root length or stem length; x2—the root length or stem length of the control; x1—the root length or stem length after treatment Experimental results:

[0066] Table 1 Pre-emergence herbicidal activity of furanoid linalool oxides and their ether derivatives against annual ryegrass

[0067]

[0068]

[0069] a Concentration (mmol·L -1 ) b Inhibition rate (%)

[0070] C: Glyphosate

[0071] Table 2 Analysis of the toxicity regression equation and IC of furanoid linalool oxides and their ether derivatives against annual ryegrass 50

[0072]

[0073] Furanoid linalool oxides (A) and their ether derivatives (B1 - B5) have strong herbicidal activity against annual ryegrass. The IC 50 values of compounds A, B1, B2, B3, B4, and B5 for the root length of annual ryegrass are 0.18 mmol / L, 0.57 mmol / L, <0.16 mmol / L, >5.0 mmol / L, 0.18 mmol / L, and 0.17 mmol / L, respectively; the IC 50 values of compounds A, B1, B2, B3, B4, and B5 for the shoot length of annual ryegrass are 0.31 mmol / L, 0.41 mmol / L, <0.16 mmol / L, 4.20 mmol / L, 0.30 mmol / L, and 0.29 mmol / L, respectively. Among them, compounds A, B2, B4, and B5 have better inhibitory ability for the shoot length of annual ryegrass than the traditional herbicide glyphosate, and their IC 50 values for the shoot length of annual ryegrass are all less than 0.41 mmol / L. Among them, the IC 50 value of compound B2 for the shoot length of annual ryegrass is less than 0.16 mmol / L, much less than the IC 50 (0.41 mmol / L) of glyphosate for the shoot length of annual ryegrass. This indicates that furanoid linalool oxides and ether derivatives have broad application prospects in pesticides represented by herbicidal activity.

[0074] Obviously, the above - mentioned embodiments are only examples for clear illustration and not limitations on the implementation manners. For those of ordinary skill in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to enumerate all implementation manners here. And the obvious changes or modifications derived therefrom are still within the protection scope of this invention.

Claims

1. A furan-type linalool oxide ether derivative, characterized in that, The structural formula is: Among them, any one of 2. The preparation method of the furanoid linalool ether derivatives according to claim 1, characterized in that, It includes the following steps: Add furfuryl linalool oxide, halogenated hydrocarbon and NaH into a solvent, and react at 90 °C to 144 °C for 1 h to 16 h to obtain furfuryl linalool oxide ether derivatives.

3. The preparation method of the furanoid linalool oxide ether derivatives according to claim 2, characterized in that, The halogenated hydrocarbon is RCl, and the is any one of them.

4. The preparation method of the furanoid linalool oxide ether derivatives according to claim 2, characterized in that, The solvent is at least one of toluene, xylene or mesitylene.

5. The preparation method of the furanoid linalool oxide ether derivatives according to claim 3, characterized in that, The molar ratio of the furfuryl linalool oxide to the halogenated hydrocarbon is 1:0.8 - 1.

2.

6. The application of the furfuryl linalool oxide ether derivatives prepared by the method for preparing the furfuryl linalool oxide ether derivatives according to claim 1 or any one of claims 2 to 5 as an active ingredient of a herbicide.

7. Use of the furanoid linalool ether derivative according to claim 6 as an active ingredient of herbicide, characterized in that, It includes the following steps: Add seeds of annual ryegrass into the solution of furfuryl linalool oxide ether derivatives and culture at 25 °C for 5 d.

8. Use of the furanoid linalool ether derivative according to claim 7 as an active ingredient of a herbicide, characterized in that, The concentration of the solution of furfuryl linalool oxide ether derivatives is 0.1563 - 5 mmol / L.

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