CN107522675A - The preparation and application of the cyanoacrylate compounds of Han oxazole bibenzyl epoxide structures - Google Patents

Abstract

The present invention relates to a kind of preparation of cyanoacrylate compounds of Han oxazoles bibenzyl epoxide structure and application (I) and its preparation method and application.Obtained with 3,3 pairs of methyl mercapto acrylate reactions of 4 (phenoxymethyl) 2 oxazolyl phenyl compound and 2 cyano group.The cyanoacrylate compound of the Han oxazoles bibenzyl epoxide structure has preferable prevention effect to weeds, and the compound can be used for the herbicide for preparing the fields such as agricultural, gardening.Formulas I structure is as follows：

Description

Preparation and Application of Cyanoacrylate Compound Containing Oxazole Bibenzyloxy Structure

technical field

The invention relates to the field of chemical pesticides, in particular to the preparation and application of a cyanoacrylate compound containing an oxazole bibenzyloxy structure.

Background technique

Herbicides are one of the most widely used pesticides. In the global herbicide market, traditional herbicides still occupy a dominant position and have made great contributions to social development. However, in recent years, with the enhancement of people's awareness of food safety and environmental protection, the status of traditional herbicides has been increasingly challenged. In view of its various drawbacks, it is imperative to find new herbicides. However, the increasingly higher herbicide standards require not only that these new herbicides can kill weeds efficiently, but also require them to be low-toxic, green and safe.

Cyanoacrylate compounds are photosystem II (PS II) electron transfer inhibitors, which can interfere with the electron transfer in the photosynthetic system of plants, so that plants cannot perform photosynthesis, thereby achieving the purpose of weeding. Such a special mechanism of action makes cyanoacrylate compounds extremely safe for animals, which meets the current market requirements for new herbicides. With the in-depth research on cyanoacrylate compounds, a large number of bioassay results show that in addition to herbicidal activity, it also has insecticidal, bactericidal, anti-plant virus, anti-tumor activities, and is a class of compounds with diverse biological activities. . In 2006, Zou Xiaomao et al. reported a cyanoacrylate compound A with good biological activity on broad-leaved weeds, and its control effect on broad-leaved weeds was more than 90% at 150g/ha (Chin.J . Org. Chem. 2006, 26, 337). In the same year, Liu Yuxiu and others reported a compound B with good biological activity against dicotyledonous weeds (Chin.J.Org.Chem., 2006, 26, 1232). In 2010, Wang Tingting et al reported compound C with good biological activity on dicotyledonous weeds (Chem. J. Chinese Universities, 2010, 31, 708).

Nitrogen-containing heterocyclic rings are a kind of active groups with special biochemical effects. As an important oxygen-containing nitrogen-containing heterocyclic ring, oxazole can be used as the electron isosteres of imidazole, pyrazole, thiazole, triazole and other groups. It is fully used in the design and development of new drugs and the improvement of the biological activity of compounds.

Therefore, in order to further search for compounds with excellent biological activity from cyanoacrylate compounds, the active group splicing method is used to rationally link the oxazole bibenzyloxy structural unit with the cyanoacrylate skeleton.

The invention discloses a kind of cyanoacrylate compound containing an oxazole bibenzyloxy structure, which has application value in agricultural weeding.

Contents of the invention

The object of the present invention is to provide a class of cyanoacrylate compounds containing oxazole bibenzyloxy structure with excellent control effect against broad-leaved weeds and grass weeds, and efficient, safe and environmentally friendly, so as to meet the needs of crops. Protect the demand for new high-efficiency herbicides.

Another object of the present invention is to provide the preparation method of the above compound.

Another object of the present invention is to provide the use of the above compounds in the preparation of herbicides.

The object of the present invention can be achieved through the following measures:

In order to solve the above technical problems, the first aspect of the present invention provides a cyanoacrylate derivative containing an oxazole bibenzyloxy structure, which has a structure of formula I,

Preferably, the cyanoacrylate compound containing the oxazole bibenzyloxy structure has the following structure:

The second aspect of the present invention provides a method for preparing a cyanoacrylate compound containing an oxazole bibenzyloxy structure, comprising the steps of:

Dissolve compound III in an organic solvent, then add intermediate II, and finally heat and react for a period of time, the reaction solution is cooled to room temperature and then suction filtered, the mother liquor is concentrated under reduced pressure, and the obtained residue is separated and purified by column chromatography to obtain the target compound.

Preferably, the organic solvent is selected from dimethyl sulfoxide, ethanol, 1,4-dioxane, acetonitrile, and carbon tetrachloride. The heating reaction temperature is 40° C. to 90° C., and the reaction time is 6 hours to 23 hours.

Preferably, the preparation method of the cyanoacrylate compound of oxazole bibenzyloxy structure comprises the steps:

Among them, the intermediate II can be synthesized by referring to the method of the literature (Chin.Chem.Lett.2014, 25, 1014); the synthesis of the intermediate 2-cyano-3,3-dimethylthioacrylic acid substituted ester III can be synthesized by referring to the literature report Conventional method (J.Agric.Food Chem.2003,51,5030).

When the compound of the present invention is used as a herbicide in fields such as agriculture and gardening, it can be used alone or in the form of a herbicidal composition, such as using the compound of formula I as an active ingredient and adding a common pesticide adjuvant in the field to be processed into water Emulsions, suspensions, water-dispersible granules, emulsifiable concentrates, etc.

Commonly used pesticide adjuvants include: liquid carriers, such as water; organic solvents such as toluene, xylene, cyclohexanol, methyl alcohol, butanol, ethylene glycol, acetone, dimethylformamide, acetic acid, dimethyl sulfoxide, animal and Vegetable oils and fatty acids; commonly used surfactants such as emulsifiers and dispersants, including anionic surfactants, cationic surfactants, nonionic surfactants and amphoteric surfactants; other additives, such as wetting agents, thickeners, etc. .

When the compound of the present invention is used as an active ingredient in a herbicide, the content in the herbicide can be selected within the range of 0.1% to 99.5%, and the appropriate active ingredient content can be determined according to the formulation form and application method. Usually, contain 5% to 50% (weight percentage, the same below) described active component in aqueous emulsion, preferably its content is 10% to 40%; Contain 5% to 50% active component in suspension concentrate, preferably Its content is 5% to 40%.

For the use of the herbicide of the present invention, common application methods can be selected, such as foliage spraying, water surface application, soil treatment and seed treatment and the like. For example, when spraying stems and leaves, the applicable concentration range of the compound represented by general formula I as the active ingredient is 75-1500g a.i./ha water emulsion, suspension concentrate, water dispersible granule, emulsifiable concentrate, preferably its concentration is 150-1500g a.i./ha.

The compound of the present invention has excellent inhibitory activity on broad-leaved weeds and grass weeds, so the compound of the present invention can be used for preparing herbicides and further protecting plants such as agriculture and gardening. The broad-leaved weeds are such as mustard greens, quinoa, etc., and the grass weeds are such as arroa, clovergrass, etc. Of course, the weeds that can be controlled by the compounds of the present invention are not limited to the above-mentioned examples.

The cyanoacrylate compound of the oxazole bibenzyloxy structure disclosed by the invention has an excellent control effect on certain broad-leaved weeds and grass weeds, and thus can be used to prepare herbicides used in fields such as agriculture and gardening.

detailed description

In order to facilitate a further understanding of the present invention, the examples provided below illustrate it in more detail. These examples are for illustration only and are not intended to limit the scope or practice principles of the present invention.

Example 1:

4mmol of compound IIIa and 6mmol of intermediate IIa were added to the reaction flask, and an appropriate amount of dimethyl sulfoxide was added, heated to 90°C, stirred for 18 hours, the solvent was evaporated under reduced pressure, and the residue was subjected to column chromatography [V (petroleum ether ): V (ethyl acetate) = 2:1] to obtain the target compound Ia; ¹ H NMR (400MHz, CDCl ₃ ): δ10.27 (s, 1H, NH), 8.03-8.07 (m, 2H, Ar- H),7.73(s,1H,Oxazole-H),7.13–7.20(m,4H,Ar-H),7.01(d,J＝8.4Hz,2H,Ar-H),5.06(s,2H,CH ₂ ), 4.71(d, J=5.6Hz, 2H, CH ₂ ), 4.29(t, J=4.8Hz, 2H, CH ₂ ), 3.65(t, J=4.8Hz, 2H, CH ₂ ), 3.40( s,3H,OCH ₃ ),2.67(s,3H,SCH ₃ ).

Example 2:

3mmol compound IIIa and 5mmol intermediate IIb were added to the reaction flask, and an appropriate amount of absolute ethanol was added, heated to reflux, stirred for 14 hours, the solvent was evaporated under reduced pressure, and the residue was subjected to column chromatography [V (petroleum ether): V ( ethyl acetate)=2:1] to obtain the target compound Ib; ¹ H NMR (400MHz, CDCl ₃ ): δ10.29 (s, 1H, NH), 7.99 (d, J=8.4Hz, 2H, Ar-H ),7.79(s,1H,Oxazole-H),7.45(d,J=8.4Hz,2H,Ar-H),7.28(d,J=2.0Hz,1H,Ar-H),7.07-7.13(m ,2H,Ar-H),5.15(s,2H,CH ₂ ),4.70(d,J=6.0Hz,2H,CH ₂ ),4.31(t,J=4.8Hz,2H,CH ₂ ),3.65( t,J＝4.8Hz,2H,CH ₂ ), 3.41(s,3H,OCH ₃ ), 2.68(s,3H,SCH ₃ ).

Example 3:

6mmol of compound IIIa and 5mmol of intermediate IIc were added to a reaction flask, and an appropriate amount of 1,4-dioxane was added, heated to 70°C, stirred for 23 hours, the solvent was evaporated under reduced pressure, and the residue was subjected to column chromatography [ V (petroleum ether): V (ethyl acetate) = 2:1] separation to obtain the target compound Ic; ¹ H NMR (400MHz, CDCl ₃ ): δ10.30 (s, 1H, NH), 8.03-8.07 (m, 2H, Ar-H), 7.78(s, 1H, Oxazole-H), 7.29(d, J=2.0Hz, 1H, Ar-H), 7.07-7.19(m, 4H, Ar-H), 5.15(s ,2H,CH ₂ ), 4.70(d,J=6.0Hz,2H,CH ₂ ),4.31(t,J=4.8Hz,2H,CH ₂ ),3.65(t,J=4.8Hz,2H,CH ₂ ),3.41(s,3H,OCH ₃ ),2.68(s,3H,SCH ₃ ).

Example 4:

3mmol of compound IIIb and 6mmol of intermediate IIb were added to the reaction flask, and an appropriate amount of anhydrous acetonitrile was added, heated to 60°C, stirred for 6 hours, the solvent was evaporated under reduced pressure, and the residue was subjected to column chromatography [V (petroleum ether): V (ethyl acetate) = 2:1] separation to obtain the target compound Id; ¹ H NMR (400MHz, CDCl ₃ ): δ10.30 (s, 1H, NH), 7.99 (d, J = 8.4Hz, 2H, Ar -H),7.79(s,1H,Oxazole-H),7.45(d,J=8.8Hz,2H,Ar-H),7.28(d,J=1.6Hz,1H,Ar-H),7.07-7.13 (m,2H,Ar-H),5.16(s,2H,CH ₂ ),4.69(d,J=5.6Hz,2H,CH ₂ ),4.29(t,J=5.6Hz,2H,CH ₂ ), 3.69(t, J=4.8Hz, 2H, CH ₂ ), 3.57(q, J=6.8Hz, 2H, CH ₂ ), 2.67(s, 3H, SCH ₃ ), 1.21(t, J=6.8Hz, 3H , CH ₃ ).

Example 5:

5mmol of compound IIIb and 9mmol of intermediate IIc were added to the reaction flask, and an appropriate amount of carbon tetrachloride was added, heated to 40°C, stirred for 20 hours, the solvent was evaporated under reduced pressure, and the residue was subjected to column chromatography [V (petroleum ether) : V (ethyl acetate) = 2: 1] separation to obtain the target compound Ie; ¹ H NMR (400MHz, CDCl ₃ ): δ10.29 (s, 1H, NH), 8.17 (d, J = 8.4Hz, 2H, Ar-H), 7.80(s, 1H, Oxazole-H), 7.73(d, J=8.4Hz, 2H, Ar-H), 7.02(d, J=8.0Hz, 1H, Ar-H), 6.79( d,J=7.2Hz,2H,Ar-H),5.15(s,2H,CH ₂ ),4.71(d,J=6.0Hz,2H,CH ₂ ),4.29(t,J=4.8Hz,2H, CH ₂ ),3.88(s,3H,OCH ₃ ),3.69(t,J=4.8Hz,2H,CH ₂ ),3.58(q,J=6.8Hz,2H,CH ₂ ),2.68(s,3H, SCH ₃ ), 1.20(t, J=6.8Hz, 3H, CH ₃ ).

Embodiment 6:

The samples were screened for activity against two broad-leaved weeds, mustard greens and quinoa, and two gramineous weeds, Amiratia and Clovergrass.

Compound configuration: Weigh a certain quality of the original drug with an analytical balance (0.0001g), dissolve it in DMF containing 1% Tween-80 emulsifier to prepare a 1.0% mother solution, and then dilute it with distilled water for later use.

Test method: pot planting method (general sieve), pre-emergence soil treatment and post-emergence stem and leaf treatment. The tested targets were mustard greens, quinoa, arpeggios and clovergrass. Take a flowerpot with an inner diameter of 7.5cm, fill it with compound soil (vegetable garden soil: seedling substrate, 1:2, v/v) to 3/4, directly sow the above four weed targets (bud rate ≥ 85%), and cover with soil 0.2cm , when the weeds grow to about 3 leaf stage, spray the stems and leaves after the emergence, while the soil treatment before the emergence is to sow and cover the soil one day before spraying and add water to keep the soil moist. According to the amount of sample provided, each compound was sprayed in the automatic spray tower (model: 3WPSH-700E) according to the dose of 1500g a.i./ha, and then the weed foliar medicine was dried and then cultured at room temperature, and the activity on weeds was investigated after 35 days (%).

Table 1. Preliminary herbicidal activity data for Ia-Ie

From the results of herbicidal activity (Table 1), it can be seen that the compounds Ia-Ie not only have good inhibitory activity on broad-leaved grasses, but also show good herbicidal activity on gramineous weeds. Under the dose of 1500g a.i./ha, compounds Ia-Ie have 100% inhibitory activity to mustard and quinoa; also under the dose of 1500g a.i./ha, compounds Ia-Ie also have moderate level of inhibitory activity to gramineous weeds, The inhibitory activities of compounds Ia-Ie on A. miltiorrhiza were 70%, 70%, 70%, 50% and 50%, respectively; the inhibitory activities of compounds Ia and Ic on A. cloverleaf were both 70%.

The above data show that the compound containing the oxazole bibenzyloxy structure and the cyanoacrylate unit is organically linked together, and the compound obtained shows better herbicidal activity, and wherein compounds Ia and Ic can be used as herbicide leads for further structural derivation and Structure-activity relationship research. This also provides an important structure selection model and theoretical basis for the molecular design, synthesis and biological activity research of new cyanoacrylate compounds in the future.

The basic principles, main features and advantages of the present invention have been shown and described above. Those skilled in the industry should understand that the present invention is not limited by the above-mentioned examples. What are described in the above-mentioned examples and descriptions are only to illustrate the principles of the present invention. The present invention also has various changes without departing from the spirit and scope of the present invention. These changes and improvements all fall within the scope of the claimed invention. The protection scope of the present invention is defined by the appended claims and their equivalents.

Claims (7)

1. a kind of preparation and application of the cyanoacrylate compound containing oxazole bibenzyloxy structure, it is characterized in that, it has the structure of formula I: 2. the cyanoacrylate compound containing oxazole bibenzyloxy structure according to claim 1, is characterized in that having following structure: 3. prepare the cyanoacrylate compound containing oxazole bibenzyloxy structure as claimed in claim 1, it is characterized in that, comprise the steps: Dissolve compound III in an organic solvent, then add intermediate II, and finally heat and react for a period of time, the reaction solution is cooled to room temperature and then suction filtered, the mother liquor is concentrated under reduced pressure, and the obtained residue is separated and purified by column chromatography to obtain the target compound. 4. preparation method according to claim 3 is characterized in that, described organic solvent is selected from dimethyl sulfoxide, ethanol, 1,4-dioxane, acetonitrile, carbon tetrachloride. The heating reaction temperature is 40° C. to 90° C., and the reaction time is 6 hours to 23 hours. 5. preparation method according to claim 3, is characterized in that, it comprises the steps: 6. the purposes of the cyanoacrylate compound containing oxazole bibenzyloxyl structure as claimed in claim 1 aspect preparation herbicide, take the compound of formula I as active ingredient, add pesticide auxiliary agent and process into water emulsion, Suspending agent, water dispersible granule, emulsifiable concentrate, etc. 7. The use according to claim 6, characterized in that: when the compound of formula I is used as an active ingredient in a herbicide, the content in the herbicide is in the range of 0.1% to 99.5%.