CN114409664A - Spiro-heterocyclic tetrahydropyran compound and preparation method and application thereof - Google Patents
Spiro-heterocyclic tetrahydropyran compound and preparation method and application thereof Download PDFInfo
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Abstract
The invention provides a spiroheterocyclic tetrahydropyran compound and a preparation method and application thereof, and the structure of the spiroheterocyclic tetrahydropyran compound is shown as a formula (I). The compound pesticide has stable chemical properties, higher insecticidal activity, excellent insecticidal activity under lower medicament concentration, particularly higher insecticidal activity on aphids and red spiders, is a novel and efficient biological pesticide, can relieve the drug resistance of plant diseases and insect pests to spirotetramat or abamectin medicaments, has very high pesticide research value, and has wide application prospect in agriculture.
Description
Technical Field
The invention relates to the technical field of agricultural chemicals and preparation, in particular to a spiroheterocyclic tetrahydropyran compound and a preparation method and application thereof.
Background
The spiro compound has a rigid structure and a stable structure, and has important application in a plurality of fields such as medicines, pesticides, polymer adhesives and the like. The two ring planes of the spiro compound are perpendicular to each other, and the heterocyclic spiro compound may have special properties which general organic compounds do not have such as spiro conjugation, spiro super conjugation or anomeric effect. Under certain conditions, due to the existence of a chiral axis, asymmetric molecules or asymmetric molecules can be formed, and the chiral spiro has strong rigidity and is not easy to racemize, which is incomparable with chiral carbon. Therefore, in recent years, spiro compounds have a wide application prospect in the fields of medicine and biology, and many spiro compounds are important intermediates of medicines and pesticides.
The spirotetramat is a spiro-compound which is more applied in the field of pesticides at present, belongs to tetronic acid compounds, belongs to the same class of compounds with spirotetramat and spirotetramat which are insecticidal acaricides of Bayer company, and is one of the insecticides with two-way systemic conductive performance so far, can effectively control various sucking mouthparts pests such as aphids, thrips, psyllids, mealybugs, whiteflies, scale insects and the like, has the advantages of broad spectrum, high efficiency and long lasting period, and is a class of pesticides which are more applied at present and used for controlling plant diseases and insect pests.
However, the effect of spirotetramat on controlling pests is remarkably reduced at a lower application concentration, and the drug resistance of pests is gradually enhanced with the increasing use of spirotetramat in recent years. Therefore, it is of great significance to design and synthesize a novel spiro compound to reduce the drug resistance of pests and diseases and provide more efficient candidate compounds for the pesticide field.
Disclosure of Invention
In order to solve the problems, the invention provides a spiroheterocyclic tetrahydropyran compound and a preparation method and application thereof.
In order to solve the technical problems, the technical scheme provided by the invention is as follows:
a spiroheterocyclic tetrahydropyran compound has a structure shown in a formula (I):
wherein R is methyl, ethyl or isopropyl; x is H, F, Cl or Br.
The novel spiroheterocyclic tetrahydropyran compound designed and synthesized by the invention has stable chemical properties, higher insecticidal activity, excellent insecticidal activity under lower medicament concentration, particularly higher insecticidal activity on aphids and red spiders, is a novel and efficient biological pesticide, can relieve the drug resistance of pests and diseases to spirotetramat or abamectin medicaments, has very high pesticide research value, and has wide application prospect in agriculture.
Preferably, the spiroheterocyclic tetrahydropyran compound has a structural formula:
the invention also provides a preparation method of the spiroheterocyclic tetrahydropyran compound, which comprises the following steps:
step a, in an inert solvent a, furfuryl alcohol and m-chloroperoxybenzoic acid are subjected to ring expansion reaction, and organic alkali are added into a system after the reaction is finished
Continuously carrying out acetylation reaction to obtain 5-carbonyl-5, 6-dihydro-2H-pyran-2-yl acetate; wherein R is1Is chloro or acetoxy;
in the step b, the step (c),in an inert solvent a, reacting 5-carbonyl-5, 6-dihydro-2H-pyran-2-yl acetate with R-OH in SnCl4Carrying out substitution reaction under catalysis to obtain a compound shown as a formula (II); wherein R is methyl, ethyl or isopropyl;
step c, in an inert solvent b, carrying out catalytic hydrogenation on the compound shown in the formula (II) to obtain a compound shown in a formula (III);
step d, carrying out Bucherer-Bergs reaction on the compound shown in the formula (III), alkali metal cyanide and ammonium salt in a polar solvent to obtain a compound shown in the formula (IV); then, carrying out hydrolysis reaction on the compound shown in the formula (IV) in an alkaline aqueous solution to obtain a compound shown in the formula (V);
step e, carrying out methyl esterification reaction on the compound shown in the formula (V) and thionyl chloride in a methanol solvent to obtain a compound shown in the formula (VI);
step f, in an inert solvent c, carrying out acylation reaction on the compound shown in the formula (VI) and the compound shown in the formula (VII) under the action of organic base to obtain the compound shown in the formula (VIII); then adding alkali metal salt into the system to continue the ring closing reaction to obtain a compound shown as a formula (IX);
and g, carrying out esterification reaction on the compound shown as the formula (IX) and ethyl chloroformate under the action of organic base to obtain the compound shown as the formula (I). The specific reaction scheme is as follows:
preferably, in step a, the inert solvent a is dichloromethane or dichloroethane, and the addition amount is 3-10 times of the mass of furfuryl alcohol.
Preferably, in the step a, the molar ratio of the m-chloroperoxybenzoic acid to the furfuryl alcohol is 1:1-1.5: 1.
Preferably, in step a, the
The molar ratio of the furfuryl alcohol to the furfuryl alcohol is 1.05:1-1.2: 1.
Preferably, in step a, the organic base is triethylamine, tetramethylethylenediamine or pyridine, and the molar ratio of the organic base to the furfuryl alcohol is 1.05:1-1.2:1
Preferably, the temperature of the ring expanding reaction and the temperature of the acetylation reaction are both 0-5 ℃, the time of the ring expanding reaction is 6-8 h, and the time of the acetylation reaction is 1.5-2 h.
Preferably, in the step b, the temperature of the substitution reaction is 20-30 ℃, and the reaction time is 3-4 h.
Preferably, in step b, the inert solvent a is dichloromethane or dichloroethane.
Preferably, in step b, the molar ratio of R-OH to furfuryl alcohol is 1:1 to 2: 1.
Preferably, in step b, SnCl4The molar ratio of the furfuryl alcohol to the furfuryl alcohol is 0.3:1-1: 1.
Preferably, in step c, the inert solvent b is ethyl acetate or tetrahydrofuran, and the amount of the inert solvent b added is 3-5 times of the amount of the compound shown in the formula (II).
Preferably, in step c, the hydrogenation catalyst is a 5% palladium-carbon catalyst, and the mass ratio of the palladium-carbon catalyst to the compound represented by the formula (II) is 0.001:1-0.01: 1.
Illustratively, in step c, the catalytic hydrogenation is carried out at ambient temperature and pressure.
Preferably, in step d, the polar solvent is water, methanol, tetrahydrofuran or ethanol, and the mass ratio of the polar solvent to the compound represented by the formula (III) is 2.0:1-5: 1.
Preferably, in step d, the alkali metal cyanide is sodium cyanide, potassium cyanide or ammonium cyanide.
Preferably, in step d, the ammonium salt is ammonium carbonate or ammonium bicarbonate.
Further preferably, in step d, the molar ratio of the compound represented by the formula (III), the alkali metal cyanide compound and the ammonium salt is 1:1:1 to 1:2: 4.
Preferably, in step d, the temperature of the Bucherer-Bergs reaction is 0 ℃ to 60 ℃ and the reaction time is 5h to 12 h.
Preferably, in the step d, the temperature of the hydrolysis reaction is 80-100 ℃, and the time of the hydrolysis reaction is 6-10 h.
In step d, the alkaline aqueous solution is 10 wt% to 20 wt% aqueous sodium hydroxide, potassium hydroxide or calcium hydroxide.
Preferably, in step d, the molar ratio of the compound represented by the formula (IV) to the base is 1:1 to 1: 1.5.
Preferably, in the step e, the temperature of the methyl esterification reaction is-5 ℃ to 0 ℃, and the reaction time is 3h to 5 h.
Preferably, in step e, the thionyl chloride is added to the solution of the compound represented by the formula (V) in a slowly dropping manner.
Preferably, in step e, the molar ratio of the compound represented by the formula (V) to thionyl chloride is 1:1-1: 1.5.
Preferably, in step a, the amount of methanol added is 3 to 10 times the amount of the compound represented by formula (V).
Preferably, in step f, the organic base is triethylamine, tetramethylethylenediamine or pyridine, and the molar ratio of the organic base to the compound shown in the formula (VI) is 1:1-1.15: 1.
Preferably, in step f, the inert solvent c is toluene, dichloromethane or dichloroethane, and the mass ratio of the inert solvent c to the compound represented by the formula (VI) is 4-10: 1.
Preferably, in step f, the alkali metal hydride salt is sodium hydride or potassium hydride, and the molar ratio of the alkali metal hydride salt to the compound shown in the formula (VI) is 2:1-2.3: 1.
Preferably, in the step f, the temperature of the acylation reaction is-5 ℃ to 0 ℃, and the reaction time is 1h to 1.5 h.
Preferably, in the step f, the temperature of the ring closing reaction is-5 ℃ to 0 ℃, and the reaction time is 3h to 5 h.
Illustratively, in step f, when X is halogen, the process for preparing the compound of formula (VII) comprises the steps of:
s101, reacting 2, 5-dimethylphenyl acetic acid with N-chlorosuccinimide in a first inert solvent for 4-6 hours at the temperature of 60-80 ℃ under the action of an initiator to obtain chloro-2, 5-dimethylphenyl acetic acid;
reacting 2, 5-dimethylphenyl acetic acid with N-bromosuccinimide in a first inert solvent for 4-6h at 60-80 ℃ under the action of an initiator to obtain bromo-2, 5-dimethylphenyl acetic acid;
s102, reacting chloro-2, 5-dimethylphenyl acetic acid or bromo-2, 5-dimethylphenyl acetic acid with sodium fluoride at 120-150 ℃ for 5-8 h in a second inert solvent to obtain fluoro-2, 5-dimethylphenyl acetic acid;
s103, reacting halogenated 2, 5-dimethylphenylacetic acid with thionyl chloride in a third inert solvent at 0-30 ℃ for 0.5-2h under the action of a catalyst to obtain a compound shown as a formula (VII);
wherein the halogenated 2, 5-dimethylphenyl acetic acid is chloro-2, 5-dimethylphenyl acetic acid or bromo-2, 5-dimethylphenyl acetic acid prepared in the step 1 or fluoro-2, 5-dimethylphenyl acetic acid prepared in the step 2.
Further, in step S101, the first inert solvent is 1, 2-dichloroethane or dimethylformamide, and the mass ratio of the first inert solvent to the 2, 5-dimethylphenylacetic acid is 4:1-10: 1.
Further, in step S101, the molar ratio of the N-chlorosuccinimide or N-bromosuccinimide to the 2, 5-dimethylphenylacetic acid is 1:1-2: 1.
Further, in step S101, the initiator is azobisisobutyronitrile, and the molar ratio of the azobisisobutyronitrile to the 2, 5-dimethylphenylacetic acid is 0.05:1-0.1: 1.
Further, in step S102, the second inert solvent is N, N-dimethylformamide or N, N-dimethylacetamide, and the mass ratio of the second inert solvent to the halogenated 2.5-dimethylphenylacetic acid is 3:1 to 6: 1.
Further, in step S102, the molar ratio of the sodium fluoride to the chloro-2, 5-dimethylphenyl acetic acid or the bromo-2, 5-dimethylphenyl acetic acid is 1:1-3: 1.
Further, in step S103, the third inert solvent is dichloromethane or 1, 2-dichloroethane, and the mass ratio of the third inert solvent to the halogenated 2, 5-dimethylphenylacetic acid is 3:1 to 10: 1.
Further, in step S103, the catalyst is N, N-dimethylformamide or N, N-dimethylacetamide, and the mass ratio of the N, N-dimethylformamide to the halogenated 2, 5-dimethylphenylacetic acid is 0.001:1 to 0.01: 1.
Further, in step S103, the molar ratio of the thionyl chloride to the halogenated 2, 5-dimethylphenylacetic acid is 1:1 to 1.5: 1.
Preferably, in step g, the organic base is triethylamine, tetramethylethylenediamine or pyridine, and the molar ratio of the organic base to the compound represented by the formula (IX) is 1.05:1-1.2: 1.
Preferably, in step g, the molar ratio of said compound of formula (IX) to ethyl chloroformate is in the range of 1:1 to 1: 1.1.
Preferably, in the step g, the temperature of the esterification reaction is-5 ℃ to 0 ℃, and the reaction time is 0.5h to 1 h.
Illustratively, in step f, when X is H, the process for preparing the compound of formula (VII) comprises the steps of:
reacting 2, 5-dimethylphenyl acetic acid with thionyl chloride in a third inert solvent for 0.5 to 2 hours at the temperature of between 0 and 30 ℃ under the action of a catalyst to obtain the compound shown in the formula (VII).
The invention also provides application of the spiroheterocyclic tetrahydropyran compound in preventing and treating plant diseases and insect pests.
Preferably, the spiroheterocyclic tetrahydropyran compound of formula (I) has a high control effect on aphids and red spiders.
The spiroheterocyclic tetrahydropyrane compound shown in the formula (I) can be applied to prevention and control of agricultural plant diseases and insect pests, and has high prevention and control effects on aphids and red spiders.
The invention also provides a pharmaceutical composition for preventing and treating aphids or red spiders, which comprises the spiroheterocyclic tetrahydropyran compound shown in the formula (I).
When the compound is used as a medicinal active ingredient for preventing and treating crop diseases and insect pests, various using methods or technologies can be provided. For example, the spiroheterocyclic tetrahydropyran compound shown in the formula (I) and conventional additives in the pesticide field are prepared into various dosage forms, such as emulsifiable concentrate, granules or powder, and the like, and the spiroheterocyclic tetrahydropyran compound is applied to roots or leaves of plants to control plant diseases and insect pests by adopting a conventional pesticide application method, such as dipping or spraying, and the like, wherein the concentration of the pesticide is 0.75mg/L-0.04mg/L, and the pesticide has higher control effect on aphids or red spiders.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
Example 1
This example provides a process for the preparation of a compound of formula (iii):
adding 500g of dichloromethane and 68.7g of furfuryl alcohol (0.7mol) into a 1L four-mouth bottle, controlling the temperature to be 0-5 ℃, adding 173g (1.0mol) of m-chloroperoxybenzoic acid, keeping the temperature and stirring for reaction for 6H, filtering to remove insoluble substances, controlling the temperature of the obtained clarified mother liquor to be 0-5 ℃, adding 80.8g (0.8mol) of triethylamine, stirring for 10min, slowly dropping 60.4g (0.77mol) of acetyl chloride, keeping the temperature and reacting for 2H after dropping, then adding 50mL of saturated sodium bicarbonate solution into the reaction liquid, stirring for 30min, separating, extracting a water layer by 30mL multiplied by 2 times by using dichloromethane, combining organic phases, and drying by anhydrous magnesium sulfate to obtain a dichloromethane solution of 5-carbonyl-5, 6-dihydro-2H-pyran-2-yl acetate;
84g (1.4mol) of isopropanol was added to a dichloromethane solution of the dried 5-carbonyl-5, 6-dihydro-2H-pyran-2-yl-acetic acid ester, and 91g (0.35mol) of SnCl was slowly dropped at room temperature4After stirring and reacting for 4 hours, 50mL of saturated sodium bicarbonate solution was added to the reaction solution, stirred for 30min, separated, and the aqueous phase was extracted with 30mL of ethyl acetate 2 timesCombining organic phases, drying the organic phases with anhydrous magnesium sulfate and concentrating the organic phases to dryness;
dissolving the obtained product with 250g of ethyl acetate, drying the product with anhydrous magnesium sulfate, adding the dried product into a 500mL reaction bottle, adding 0.5g of 5% Pd/C catalyst, adding a hydrogen balloon into the reaction bottle, providing hydrogen by the hydrogen balloon, stirring the mixture at room temperature for reaction for 1.5h, filtering the reaction product to remove the catalyst, concentrating the mother liquor, purifying the mother liquor by column chromatography (eluent is ethyl acetate and n-hexane with the volume ratio of 10: 1), and distilling the eluent under reduced pressure to obtain colorless oily matter, namely 75.2g of the compound shown in the formula (II) (namely the compound IIa), wherein the yield is 68% and the purity is 99.5%.
And (3) concentrating and drying a small amount of the colorless oily reaction product, and then carrying out structure confirmation:
1HNMR(DMSO)δppm：4.58(dd,J1＝8.2,J2＝3.5,2H),4.20(t,J＝2.2,lH),3.19(m,1H),2.50(m,2H),2.0(m,lH),1.75(m,lH),1.13(s,3H),1.10(s,3H)。
LC-MS[M+H]+：159.10。
the compound shown in the formula (II) can be prepared by adopting other reaction conditions, reaction solvents and the like which are limited in the specification of the invention, and the technical effect basically equivalent to the technical effect can be achieved.
Examples 2 to 3
The synthesis of compounds IIIb and IIIc proceeds as described above, with specific process parameters routinely adjusted as in example 1.
Example 4
Preparation of a Compound of formula (IV):
120g (1.52mol) of ammonium bicarbonate and 20g (0.4mol) of sodium cyanide are weighed and added into a mixed solution of 30g of water and 100g of tetrahydrofuran, the mixture is stirred and suspended, 60.6g (0.38mol) of the compound II a prepared in example 3 is added at room temperature, after the mixture is uniformly mixed, the temperature is raised to 55 ℃, the reaction is kept for 6 hours, the filtration is carried out, a filter cake is washed by 20g of tetrahydrofuran, mother liquor is combined, the mother liquor is concentrated to be dry, and the drying is carried out, thus 85.7g of white solid (compound IVa) is obtained, the yield is 98 percent, and the purity is 96.2 percent.
The synthesis of the compounds IVb and IVc is carried out according to the above-mentioned methods, and the specific process parameters can be obtained by routine adjustment according to the above-mentioned examples.
Example 5
Preparation of a compound represented by the formula (VII):
preparation of 3-chloro-2, 5-dimethylbenzyl acetate and 4-chloro-2, 5-dimethylbenzyl acetate:
weighing 16.4g of 2, 5-dimethylphenylacetic acid, placing the mixture into a 250mL reaction bottle, adding 80g of 1, 2-dichloroethane, 15g N-chlorosuccinimide, 0.9g of azobisisobutyronitrile and 30g of dimethylformamide, reacting for 5h at 80 ℃, filtering, concentrating mother liquor, performing column chromatography (eluent is a mixed solution of dichloromethane, methanol and glacial acetic acid with the volume ratio of 20:1: 0.001), and evaporating and concentrating to obtain 9.6g of 3-chloro-2.5-dimethylphenylacetic acid and 7.0g of 4-chloro-2.5-dimethylphenylacetic acid.
Preparation of 3-bromo-2, 5-dimethylphenylacetic acid and 4-bromo-2, 5-dimethylphenylacetic acid:
weighing 16.4g of 2, 5-dimethylphenylacetic acid, placing the mixture into a 250mL reaction bottle, adding 80g of 1, 2-dichloroethane, 20.2g N-bromosuccinimide, 0.9g of azobisisobutyronitrile and 30g of dimethylformamide, reacting for 5h at 80 ℃, filtering, concentrating mother liquor, performing column chromatography (eluent is a mixed solution of dichloromethane, methanol and glacial acetic acid with the volume ratio of 20:1: 0.001), and evaporating and concentrating to obtain 12.2g of 3-bromo-2.5-dimethylphenylacetic acid and 9.7g of 4-bromo-2.5-dimethylphenylacetic acid.
Preparation of 3-fluoro-2, 5-dimethylphenylacetic acid:
putting 9.6g of 3-chloro-2, 5-dimethylphenylacetic acid into a 100mL reaction bottle, adding 40g of dimethylformamide and 4.0g of sodium fluoride, uniformly mixing, reacting at 150 ℃ for 5h, pouring the reaction liquid into 200mL of ice water, extracting with 50mL of acetic acid by multiplying by 3 times, combining organic phases, and drying by anhydrous magnesium sulfate to obtain 7.1g of 3-fluoro-2.5-dimethylphenylacetic acid.
Preparation of 3-chloro-2, 5-dimethylbenzeneacetyl chloride:
weighing 9.6g of 3-chloro-2, 5-dimethylphenylacetic acid, placing the weighed 3-chloro-2, 5-dimethylphenylacetic acid in a 100mL reaction bottle, adding 40g of dichloromethane and 0.1g of dimethylformamide, slowly dripping 7.0g of thionyl chloride at the temperature of 30 ℃, stirring for 2h under heat preservation, and concentrating under reduced pressure to obtain yellow oily matter, namely 10.6g of 3-chloro-2, 5-dimethylphenylacetyl chloride, wherein the yield is 95 percent, and the purity is 95 percent.
Other compounds represented by the formula (VII) can be prepared by adopting other halogenated-2, 5-dimethylphenyl acetic acid according to the method, and the specific process conditions can be adjusted by the conventional method according to the 3-chloro-2, 5-dimethylphenyl acetyl chloride.
Example 6
84.4g (0.37mol) of the compound IVa prepared in example 4 is taken and added into a reaction bottle, 222g of 10 wt% sodium hydroxide aqueous solution is added, the temperature is increased to 80 ℃ for reaction for 10h, the temperature is reduced to 0 ℃, the pH value is adjusted to 6.5-7.2 by using 5 wt% diluted hydrochloric acid, the mixture is stirred for 30min under the condition of heat preservation, and the mixture is concentrated to obtain an earthy yellow solid, namely 70.0g of the compound shown in the formula (Va), the yield is 93%, and the purity is 98.2%.
The synthesis of compound vb and compound vc is carried out according to the methods described above, and the specific process parameters can be routinely adjusted as described in the examples above.
Example 7
Preparation of a compound of formula VI:
63.8g (0.31mol) of the compound Va prepared in example 6 is added into a 500mL four-mouth bottle, 200g of methanol is added, the temperature is reduced to minus 5 ℃ to 0 ℃, 44.8g (0.38mol) of thionyl chloride is slowly dripped, the temperature is controlled not to exceed 0 ℃, the temperature is kept for reaction for 3 hours after the dripping is finished, and 73.5g of yellow solid, namely the compound VIa, is obtained after the reaction is finished and is dried.
Adding 63.4g (0.25mol) of compound VIa into a four-mouth bottle, adding 300g of toluene, slowly adding 46.6g (0.256mol) of 2, 5-dimethyl phenylacetyl chloride dropwise, cooling to-5-0 ℃, slowly adding 28g (0.277mol) of triethylamine dropwise, keeping the temperature for reaction for 1h after the dropwise addition is finished, then slowly adding 20g (0.5mol) of sodium hydride solid with the content of 60 wt%, keeping the temperature for reaction for about 3h after the addition is finished, slowly adding dilute hydrochloric acid dropwise to adjust the pH to 3-4 after the detection of the reaction of raw materials is finished, stirring for 10min at room temperature, separating liquid, drying the organic phase by anhydrous magnesium sulfate, adding 35g (0.30mol) of tetramethyl ethylenediamine into the dried organic phase, cooling to-5-0 ℃, slowly adding 27.1g (0.25mol) of ethyl chloroformate dropwise, controlling the reaction temperature to be not higher than 0 ℃, reacting for 30min after the dropwise addition is finished, adding 50mL of water into a system after the reaction is finished, stirring for 30min, separating, and spin-drying the organic phase to obtain 88.5g of light yellow solid, namely the compound (marked as compound Ia) shown in the formula I, wherein the yield is 86%, and the content is 98%.
Product structure identification data:
1H NMR(CDCl3)δppm：8.01(s,1H),7.04(m,3H),4.96(t,J＝3.26,1H),4.20(q,J＝2.26,2H),4.08(m,4H),3.20(m,1H),2.48(s,3H),2.40(s,3H),1.90(m,4H),1.29(t,J＝3.36,3H),1.24(m,6H)。
13C NMR(CDCl3)δppm：165.5,153.8,147.5,134.6,132.4,129.0,128.3,126.8,107.7,98.5,67.4,63.7,62.5,54.1,26.2,22.8,23.3,21.3,14.5,13.3。
LC-MS[M+H]+: 403.46, respectively; the calculated values are: 403.46.
examples 8 to 12
The synthesis of compounds Ib to if was carried out in accordance with the method described above, the specific process parameters being adjusted as usual in example 7.
Test of drug efficacy
Toxicity of the compound shown in the formula (I) prepared in the embodiments 7-12 of the invention, avermectin and spirotetramat to broad bean aphids and cotton red spiders is measured indoors, and insecticidal activity is evaluated in a comparative way.
Test conditions
1.1 test target
Broad bean sprouts (Aphis fabae) are indoor sensitive strains fed with broad bean seedlings for many years, and the experimental insects are 3-day-old Aphis.
The spider mite (tetranychusurtica) is a sensitive strain which is bred for many years indoors by broad bean seedlings, and the test insects are healthy adult mites.
1.2 culture conditions
The culture conditions for the test target and the post-test target were 25. + -. 5 ℃ temperature, 65. + -. 5% relative humidity, and 12/12h (L/D) light cycle.
Test method
2.1 test Agents
The compound Ia, the compound Ib, the compound Ic, the compound Id, the compound Ie, the compound If, the abamectin and the spirotetramat compound are all provided by Hebei Wenyuan biochemical engineering Co., Ltd.
2.2 preparation of the medicament
Test agents are prepared into agents with different concentrations by taking N, N-dimethylformamide as a solvent, Tween-80 as an emulsifier and water as a diluent. Wherein, the content of N, N-dimethylformamide in the medicament is 0.2 wt%, and the content of Tween-80 is 0.2 wt%.
The concentrations of the agents used as test targets for aphids were 0.75mg/L, 0.1875mg/L, 0.046875 mg/L.
The concentrations of the test agents for the test targets of Aranea gossypii were 0.75mg/L, 0.1875mg/L, and 0.046875 mg/L.
2.3 test procedure
Refer to "evaluation of pesticide biological Activity SOP".
The broad bean aphids adopt an immersion method. Cutting off broad bean seedlings with 3-day-old broad bean aphids, putting the broad bean seedlings into the prepared medicament, soaking the broad bean seedlings for 15 seconds, taking out the broad bean seedlings, sucking redundant liquid medicine around plants and insect bodies by using filter paper, inserting the plants and the insect bodies on water-sucking sponges, covering a horse-shaped lampshade, and repeating the treatment for 3 times. After the treatment, the cells are placed in a recovery room for culture, the cells are observed regularly, the death condition is checked and recorded after 48 hours, and the death rate is calculated.
The Aranea is sprayed with the liquid. Pulling out two-leaf and one-heart-stage silkworm seedlings with adult red spiders from roots, placing the two-leaf and one-heart-stage silkworm seedlings into a beaker filled with clear water, sealing the opening of the beaker by using a parafilm sealing film, clamping a plastic gasket, and carrying out spraying treatment by using an electric throat sprayer, wherein the spraying amount is 2 mL/plant, and the treatment is repeated for 4 times. After the plants are dried, a horse lamp cover is covered, the plants are placed in a recovery room for culture, the death condition is checked and recorded after 72 hours, and the death rate is calculated.
3. Investigation method and biological activity evaluation method
3.1 investigation method
And (5) checking the death condition of the test insects after 72h, and recording, wherein the judgment standard of the death of the test insects is as follows: no response was noted as death by gentle contact of the test insects with a writing brush.
3.2 evaluation method of biological Activity
The initial screening with a mortality rate above 50% at the lowest concentration can be considered for further screening.
4. Analysis of results
The results of the aphid-killing activity assay for the test agents at different concentrations are shown in table 1.
TABLE 1 mortality of aphids at different concentrations of test agent
As can be seen from the above table, compound Ib, compound Ie and compound If have high insecticidal activity against aphids, wherein compound Ie has the highest insecticidal activity, and the lethality of the target pests at the three test doses of the initial screening is 94.54%, 85.59% and 65.89%, and the lethality of the target pests at the three test doses of the initial screening is 86.75%, 47.73% and 40.26% respectively with compound Ib. And under the condition of low medicament concentration (0.1875mg/L and 0.046875mg/L), the insecticidal activity to aphid is obviously superior to that of abamectin and spirotetramat.
The results of the determination of the insecticidal activity of the test agents on spider mites are shown in Table 1.
TABLE 2 mortality of Aranea gossypii at different concentrations of test agent
| Experimental number | Compound numbering | 0.75(mg/L) | 0.1875(mg/L) | 0.046875(mg/L) |
| 1 | Ia | 95.10 | 32.80 | 10.80 |
| 2 | Ib | 97.73 | 41.99 | 24.67 |
| 3 | Ic | 100.00 | 28.55 | 5.20 |
| 4 | Id | 95.76 | 39.63 | 11.14 |
| 5 | Ie | 97.14 | 77.58 | 57.69 |
| 6 | If | 92.76 | 34.38 | 12.83 |
| 7 | Spirotetramat | 78.47 | 61.39 | 24.90 |
| 8 | Abamectin and its preparation method | 100.00 | 100.00 | 98.48 |
As can be seen from the above table, only compound Ib, compound Ie and abamectin in the test sample have high insecticidal activity against the cotton red spider, wherein the lethality of the target pest under the three test doses of the compound Ie in the primary screening is 97.14%, 57.58% and 37.69%, respectively. And still has higher insecticidal activity under low medicament concentration (0.1875mg/L and 0.046875 mg/L).
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents or improvements made within the spirit and principle of the present invention should be included in the scope of the present invention.
Claims (10)
1. A spiroheterocyclic tetrahydropyran compound, characterized in that it has the structure shown in formula (I):
wherein R is methyl, ethyl or isopropyl; x is H, F, Cl or Br.
2. A spiroheterocyclic tetrahydropyran compound according to claim 1 having the formula:
3. a process for the preparation of a spiroheterocyclic tetrahydropyran compound according to claim 1 or 2, characterized by comprising the steps of:
step a, in an inert solvent a, furfuryl alcohol and m-chloroperoxybenzoic acid are subjected to ring expansion reaction, and organic alkali are added into a system after the reaction is finished
Continuously carrying out acetylation reaction to obtain 5-carbonyl-5, 6-dihydro-2H-pyran-2-yl acetate; wherein R is1Is chloro or acetoxy;
step b, in an inert solvent a, 5-carbonyl-5, 6-dihydro-2H-pyran-2-yl acetate and R-OH are reacted in SnCl4Carrying out substitution reaction under catalysis to obtain a compound shown as a formula (II); wherein R is methyl, ethyl or isopropyl;
step c, in an inert solvent b, carrying out catalytic hydrogenation on the compound shown in the formula (II) to obtain a compound shown in a formula (III);
step d, carrying out Bucherer-Bergs reaction on the compound shown in the formula (III), alkali metal cyanide and ammonium salt in a polar solvent to obtain a compound shown in the formula (IV); then, carrying out hydrolysis reaction on the compound shown in the formula (IV) in an alkaline aqueous solution to obtain a compound shown in the formula (V);
step e, carrying out methyl esterification reaction on the compound shown in the formula (V) and thionyl chloride in a methanol solvent to obtain a compound shown in the formula (VI);
step f, in an inert solvent c, carrying out acylation reaction on the compound shown in the formula (VI) and the compound shown in the formula (VII) under the action of organic base to obtain the compound shown in the formula (VIII); then adding alkali metal salt into the system to continue the ring closing reaction to obtain a compound shown as a formula (IX);
and g, carrying out esterification reaction on the compound shown as the formula (IX) and ethyl chloroformate under the action of organic base to obtain the compound shown as the formula (I).
4. A process for preparing a spiroheterocyclic tetrahydropyran compound according to claim 3, wherein in step a and step b, the inert solvent a is dichloromethane or dichloroethane; and/or
In the step a, the step f and the step g, the organic base is triethylamine, tetramethylethylenediamine or pyridine; and/or
In the step a, the temperature of ring expanding reaction and acetylation reaction is 0-5 ℃, the time of ring expanding reaction is 6-8 h, and the time of acetylation reaction is 1.5-2 h.
5. A process for the preparation of a spiroheterocyclic tetrahydropyran compound according to claim 3, wherein in step b, the temperature of said substitution reaction is 20 ℃ to 30 ℃ and the reaction time is 3h to 4 h; and/or
In the step c, the inert solvent b is ethyl acetate or tetrahydrofuran.
6. A process for the preparation of a spiroheterocyclic tetrahydropyran compound according to claim 3, wherein in step d, said polar solvent is water, methanol or ethanol; and/or
In step d, the alkali metal cyanide is sodium cyanide, potassium cyanide or ammonium cyanide; and/or
In the step d, the ammonium salt is ammonium carbonate or ammonium bicarbonate; and/or
In the step d, the temperature of the Bucherer-Bergs reaction is 0-60 ℃, and the reaction time is 5-12 h; and/or
In the step d, the temperature of the hydrolysis reaction is 80-100 ℃, and the time of the hydrolysis reaction is 6-10 h.
7. A process for the preparation of a spiroheterocyclic tetrahydropyran compound according to claim 3, wherein in step e, the methyl esterification reaction is carried out at a temperature of-5 ℃ to 0 ℃ for a reaction time of 3h to 5 h; and/or
In the step f, the inert solvent c is toluene, dichloromethane or dichloroethane; and/or
In the step f, the temperature of the acylation reaction is-5 ℃ to 0 ℃, and the reaction time is 1h to 1.5 h; and/or
In the step f, the temperature of the ring closing reaction is-5 ℃ to 0 ℃, and the reaction time is 3h to 5 h; and/or
In the step g, the temperature of the esterification reaction is-5 ℃ to 0 ℃, and the reaction time is 0.5h to 1 h.
8. Use of spiroheterocyclic tetrahydropyran compounds according to claim 1 or 2 for controlling plant pests.
9. Use according to claim 8, wherein the spiroheterocyclic tetrahydropyran compound is used for controlling aphids and red spiders.
10. A pharmaceutical composition for controlling aphids or red spiders, comprising the spiroheterocyclic tetrahydropyran compound according to claim 1 or 2.
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