CN108203450B - Preparation method and application of amino phosphonate containing arylpyrazole compound - Google Patents
Preparation method and application of amino phosphonate containing arylpyrazole compound Download PDFInfo
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- C07F9/65586—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system at least one of the hetero rings does not contain nitrogen as ring hetero atom
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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- A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
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- A01N57/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds
- A01N57/18—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds having phosphorus-to-carbon bonds
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Abstract
本发明公开了含氨基膦酸酯和芳基呋喃结构的芳基吡唑类化合物的制备方法及应用，其为结构通式(I)的化合物。本发明化合物使用量少，杀虫效率高，工艺方法简单，成本低廉，具有广阔的市场前景。 The invention discloses a preparation method and application of an arylpyrazole compound containing an amino phosphonate and an arylfuran structure, which is a compound of general structural formula (I). The compound of the invention is used in a small amount, has high insecticidal efficiency, simple process method and low cost, and has broad market prospect.
Description
Technical Field
The invention belongs to the field of pesticides, and particularly relates to a preparation method of an arylpyrazole compound containing aminophosphonate and arylfuran structures and application of the arylpyrazole compound as a pesticide.
Background
Pesticides make great contribution to modern agricultural production, but some traditional pesticides are frequently blamed for environmental toxicity, safety and drug resistance, and the development of safe, green and efficient new pesticides becomes a research hotspot of current pesticide chemistry. The arylpyrazole compounds represented by fipronil have very important roles in modern agriculture due to the characteristics of broad spectrum, high efficiency, low toxicity, low residue and the like. Fipronil has stomach toxicity as main action on pests, has contact killing and systemic action, and has the action mechanism of hindering chloride metabolism controlled by gamma-aminobutyric acid (GABA), influencing normal synaptic transmission of a central nervous system, enhancing the excitation of the nervous system, causing nerve dysfunction and leading to death of the pests. Fipronil has high insecticidal activity on aphids, leafhoppers, plant hoppers, lepidoptera larvae, flies, coleoptera and other important pests, and has no phytotoxicity on crops. However, the drug resistance detection of the Tangjian et al shows that the drug resistance of the most common rice Pest, namely the white back planthopper in Asian regions, to the fipronil reaches 50.5 times (Tang, J.et, Pest Manag.Sci.2010; 66: 121-125), and in addition, the common agricultural pests, namely the cotton bollworms, the diamond back moths and the like, also have certain drug resistance and drug resistance to the arylpyrazole insecticides, namely the fipronil and the like. The development of novel arylpyrazole insecticides which have high efficiency and low toxicity and can better prevent and control pests is an important subject for the development of new pesticides.
the alpha-aminophosphonate as the analogue of natural aminophosphonic acid can imitate natural amino acid in organism, deeply affect the metabolism of various enzymes and proteins, has structural similarity with phosphorylated amino acid and polypeptide hydrolysate, and is commonly used for sterilization, anti-tumor, weeding, enzyme activity inhibition and plant virus resistance.
The aryl furan ring is a high-conjugation and electron-rich structure, is a common structural unit in medicinal chemistry, is often used as a good pharmacophore to be introduced into a lead compound, effectively enhances the biological activity of the lead compound by improving the electron cloud distribution of the lead compound, and is often used as an antibacterial agent, a plant growth regulator and the like.
Through domestic and foreign literature search, in the prior art, the arylpyrazole compound containing aminophosphonate and arylfuran structures, the structure of which is shown as the general formula (I) in the invention, is not reported.
The invention discloses an arylpyrazole derivative containing aminophosphonate and arylfuran structures, which is prepared based on the excellent insecticidal activity of arylpyrazole compounds and by adopting an activity splicing principle and carrying out structural modification on arylpyrazole by aminophosphonate and arylfuran according to a new pesticide preparation principle.
Disclosure of Invention
The invention aims to provide an arylpyrazole compound containing an aminophosphonate and a phenyl furan structure.
The invention also aims to provide a preparation method of the compound and application of the compound in preparing pesticides.
The object of the invention can be achieved by the following measures:
preparing a compound with a structural general formula (I),
wherein R is1、R2And R3Each independently of the others is hydrogen, halogen, C1-C3Alkyl radical, C1-C3Alkoxy or C1-C3A haloalkyl group.
The compounds of the invention are preferably selected from:
a process for the preparation of a compound of formula (I) according to claim 1, by the reaction:
wherein R is1、R2And R3Each independently of the others is hydrogen, halogen, C1-C3Alkyl radical, C1-C3Alkoxy or C1-C3A haloalkyl group.
The reaction is carried out in a solvent. Wherein the solvent of the first step reaction (A) is a protic solvent: water or alcohols, such as methanol, ethanol, water, preferably water; wherein the solvent of the second reaction (B) is a protic solvent: water or alcohols, such as water or ethanol, preferably water; the solvent for the third step reaction (C) is a protic solvent: water or alcohols, such as water or ethanol, preferably water; the solvent for the fourth step reaction (D) is a non-polar solvent: benzene or a halogenated hydrocarbon, preferably toluene; the solvent for the fifth reaction (E) is reactant diethyl phosphite, preferably diethyl phosphite.
The reaction temperature in the reaction A is-15 ℃ to 50 ℃, and preferably-10 ℃ to 5 ℃; the reaction temperature in the reaction B is 0-50 ℃, and preferably 0-25 ℃; the reaction temperature in the reaction C is 0-50 ℃, and preferably 0-15 ℃; the reaction temperature in the reaction D is 50-110 ℃, and preferably 90-110 ℃; the reaction temperature in the reaction E is 30 to 90 ℃, preferably 50 to 80 ℃.
The compound of the invention can be applied to the preparation of pesticides. The compounds of the general formula (I) according to the invention can be used as pesticides alone or in the form of formulations with auxiliary agents in order to increase their insecticidal efficacy.
The invention also discloses an insecticidal composition, which is characterized by comprising the compound of the general formula (I) in the claim 1 as an active ingredient and an agriculturally acceptable carrier. The composition can be made into pesticide aerosol.
The insecticidal aerosol contains 0.1-70 wt% of solvent and 28-99.88 wt% of propellant besides the compound of the general formula (I) of the invention. The solvent is C10～C18The alkane solvents such as D60, D80 and D110 solvent oil; water; c2～C8And (3) one or more of small molecule alcohol solvents.
The compound of the invention has the advantages of small dosage, good insecticidal effect, simple synthesis process and wide application prospect.
The following representative test procedures were conducted using the compounds obtained in the examples of the present invention to determine the insecticidal activity of the compounds of the present invention.
Culex insecticidal effect (aerosol)
The compounds 1 to 13 obtained in examples were each formulated into an aerosol according to the method of example 41.
The method is characterized in that a standard testing cylinder is adopted, testing is carried out according to the specification of GB 13917.2-2009, culex pipiens to be tested is placed in a brown bottle, 1g of medicament is quantitatively sprayed from an insecticidal aerosol, a baffle is drawn out after 1min to enable the medicament to be contacted with insects, timing is carried out immediately, the number of knocked down insects is recorded, after 20min, the culex pipiens to be tested is transferred to a clean insect cage, and after 24h, the number of dead insects is checked.
At a concentration of 0.1% (based on the active compound content), the mortality rate for each treatment was calculated for 24h according to the survey data, specifying the activity grading criterion: a level: the death rate is less than 100 percent within 90 percent to 24 hours; b stage: the mortality rate is less than 90 percent within 75 percent to 24 hours; c level: the mortality rate is less than 75 percent after 24 hours with the concentration of 50 percent to less than or equal to 24 hours; d stage: the mortality rate is less than 50 percent within 25 percent to 24 hours; e, grade: the mortality rate is less than 25 percent after 24 hours with the time being more than or equal to 0.
The test result shows that: 4 of the 11 compounds with A-grade activity are respectively compound 10, compound 11, compound 12 and compound 13; 3B stages are respectively compound 1, compound 3 and compound 4; the C-level activity is 4, and the C-level activity is compound 2, compound 5, compound 6 and compound 7; the activity of the D grade is 1, and the D grade is a compound 8; grade E, 1 active substance, is compound 9.
Detailed Description
Example 1
This example illustrates the preparation of 5- (4-chlorophenyl) furan-2-carbaldehyde
A250 mL round-bottom three-necked flask was charged with 0.01mol of 4-chloroaniline and a small amount of ethanol, and 3.0mL (0.035mol) of concentrated hydrochloric acid was added dropwise with stirring under ice-bath conditions. 0.018mol of sodium nitrite is dissolved in 10mL of water, slowly dropped into the flask, and reacted for 0.5h after the dropping is finished to obtain yellow diazonium salt solution.
Dissolving 0.01moL of furfural in 10mL of acetone, stirring for 30 minutes, dropping the prepared diazonium salt solution into a flask, keeping the temperature of the system at 10 ℃ in an ice-water bath, and reacting for 3 hours. After the reaction, washing with water (2X 30mL) and saturated sodium chloride solution (1X 40mL), filtering to obtain a crude product, recrystallizing with ethanol to obtain 1.22g of a product, wherein the yield is 53.6%, and the melting point of the product is as follows: 117-119 ℃.
Example 2
This example illustrates the preparation of 5-amino-1- (2-fluorophenyl) -3-cyano-1H-pyrazole
A250 mL round-bottom three-necked flask was charged with 0.01mol of 2-fluoroaniline and a small amount of ethanol, and 3.0mL (0.035mol) of concentrated hydrochloric acid was added dropwise with stirring under ice-bath conditions. 0.018mol of sodium nitrite is dissolved in 10mL of water, slowly dropped into the flask, and reacted for 0.5h after the dropping is finished to obtain yellow diazonium salt solution.
Adding 0.01mol of 2, 3-dicyanopropionic acid ethyl ester into a three-neck flask, and dripping the prepared diazonium salt solution into the flask to finish the reaction for 2 hours. Adding ammonia water, adjusting the pH value to 9-10, and reacting for 2h at room temperature. After the reaction, the mixture was extracted with 40mL of dichloromethane, the organic layer was washed with water (2X 30mL), the organic layer was washed with a saturated sodium chloride solution (1X 40mL), dried over anhydrous magnesium sulfate, and a portion of the solvent was evaporated under reduced pressure to crystallize out, whereby 1.26g of the product was obtained, the yield was 62.3%, and the melting point of the product was: 196 to 198 ℃.
Example 3
This example illustrates the preparation of 5- (((4-chlorophenyl) furan-2-methylene) amino) -1- (2-fluorophenyl) -1H-pyrazole-3-carbonitrile
In a 100mL four-necked flask, 0.01mol of 5-amino-1- (2-fluorophenyl) -3-cyano-1H-pyrazole, 40mL of toluene and 5 drops of piperidine were added, and dissolved by stirring, and then a condenser tube and a Dean-Stark trap were attached to reflux the mixture, and a toluene solution in which 5.5mmol of 5- (4-chlorophenyl) furan-2-carbaldehyde was dissolved was added dropwise to react for 2 hours. After the reaction is finished, most of toluene is removed by reduced pressure rotary evaporation, and the crude product is obtained by cooling crystallization and filtration. The crude product was recrystallized from 5mL of toluene to give the final product in 82.5% yield. Melting point of the product: 192-194 ℃.
Example 4
This example illustrates the preparation of diethyl (5- (4-chlorophenyl) furan-2-methylidene) ((3-cyano-1- (2-fluorophenyl) -1H-pyrazol-5-yl) amino) phosphonate
A50 mL four-necked flask was charged with 0.002mol of 5- (((4-chlorophenyl) furan-2-methylene) amino) -1- (2-fluorophenyl) -1H-pyrazole-3-carbonitrile and 5mL of diethyl phosphite, and the reaction was stirred at 80 ℃. After the reaction, the excessive diethyl phosphite is removed by reduced pressure rotary evaporation to obtain a crude product. The crude product was recrystallized from 3mL of methanol to give a white solid, 0.63g of final product, 59.3% yield. Melting point of the product: 120-121 ℃;1H NMR(CDCl3，δ)：δ7.56-7.45(m，4H，phenyl-H)，7.37-7.28(m，4H，phenyl-H)，6.62(d，J＝3.3Hz，1H，furan-H)，6.50(t，J＝3.0Hz，1H，furan-H)，5.93(s，1H，pyrazole-H)，4.70(d，J＝8.7Hz，1H，-NH-)，4.63(d，J＝8.5Hz，1H，P-CH)，4.13(m，2H，-CH2-)，4.05(m，1H，-CH2-)，3.90(m，1H，-CH2-)，1.29(t，J＝7.0Hz，3H，-CH3)，1.17(t，J＝7.0Hz，3H，-CH3).
example 5
This example illustrates the preparation of 5-amino-1- (3-fluorophenyl) -3-cyano-1H-pyrazole
A250 mL round-bottom three-necked flask was charged with 0.01mol of 3-fluoroaniline and a small amount of ethanol, and then 3.0mL (0.035mol) of concentrated hydrochloric acid was added dropwise with stirring under ice-bath conditions. 0.018mol of sodium nitrite is dissolved in 10mL of water, slowly dropped into the flask, and reacted for 0.5h after the dropping is finished to obtain yellow diazonium salt solution.
Adding 0.01mol of 2, 3-dicyanopropionic acid ethyl ester into a three-neck flask, and dripping the prepared diazonium salt solution into the flask to finish the reaction for 2 hours. Adding ammonia water, adjusting the pH value to 9-10, and reacting for 2h at room temperature. After the reaction, the mixture was extracted with 40mL of dichloromethane, the organic layer was washed with water (2X 30mL), the organic layer was washed with a saturated sodium chloride solution (1X 40mL), dried over anhydrous magnesium sulfate, and a portion of the solvent was evaporated under reduced pressure to crystallize out, whereby 1.18g of the product was obtained, the yield was 58.3%, and the melting point of the product was: 188-190 ℃.
Example 6
This example illustrates the preparation of 5- (((4-chlorophenyl) furan-2-methylene) amino) -1- (3-fluorophenyl) -1H-pyrazole-3-carbonitrile
In a 100mL four-necked flask, 0.01mol of 5-amino-1- (3-fluorophenyl) -3-cyano-1H-pyrazole, 40mL of toluene and 5 drops of piperidine were added, and dissolved by stirring, and then a condenser tube and a Dean-Stark trap were attached to reflux the mixture, and a toluene solution in which 5.5mmol of 5- (4-chlorophenyl) furan-2-carbaldehyde was dissolved was added dropwise to react for 2 hours. After the reaction is finished, most of toluene is removed by reduced pressure rotary evaporation, and the crude product is obtained by cooling crystallization and filtration. The crude product was recrystallized from 5mL of toluene to give the final product in 90% yield. Melting point of the product: 200-202 ℃.
Example 7
This example illustrates the preparation of diethyl (5- (4-chlorophenyl) furan-2-methylidene) ((3-cyano-1- (3-fluorophenyl) -1H-pyrazol-5-yl) amino) phosphonate
A50 mL four-necked flask was charged with 0.002mol of 5- (((4-chlorophenyl) furan-2-methylene) amino) -1- (3-fluorophenyl) -1H-pyrazole-3-carbonitrile and 5mL of diethyl phosphite, and the reaction was stirred at 80 ℃. After the reaction, the excessive diethyl phosphite is removed by reduced pressure rotary evaporation to obtain a crude product. The crude product was recrystallized from 3mL of methanol to give a white solid, 0.72g of final product, 68.3% yield. Melting point of the product: 116-117 ℃;1H NMR(CDCl3，δ)：δ7.52(dd，J＝18.9，8.2Hz，3H，phenyl-H)，7.35(dd，J＝15.2，6.9Hz，4H，phenyl-H)，7.19(dd，J＝8.2，6.8Hz，1H，phenyl-H)，6.63(d，J＝3.2Hz，1H，furan-H)，6.50(t，J＝3.0Hz，1H，furan-H)，5.95(s，1H，pyrazole-H)，4.81(m，1H，-NH-)，4.66(dd，J＝22.4，8.6Hz，1H，P-CH)，4.19(m，2H，-CH2-)，4.07(dt，J＝21.6，7.1Hz，1H，-CH2-)，3.93(m，1H，-CH2-)，1.34(t，J＝7.1Hz，3H，-CH3)，1.19(t，J＝7.0Hz，3H，-CH3).
example 8
This example illustrates the preparation of 5-amino-1- (4-fluorophenyl) -3-cyano-1H-pyrazole
A250 mL round-bottom three-necked flask was charged with 0.01mol of 4-fluoroaniline and a small amount of ethanol, and 3.0mL (0.035mol) of concentrated hydrochloric acid was added dropwise with stirring under ice-bath conditions. 0.018mol of sodium nitrite is dissolved in 10mL of water, slowly dropped into the flask, and reacted for 0.5h after the dropping is finished to obtain yellow diazonium salt solution.
Adding 0.01mol of 2, 3-dicyanopropionic acid ethyl ester into a three-neck flask, and dripping the prepared diazonium salt solution into the flask to finish the reaction for 2 hours. Adding ammonia water, adjusting the pH value to 9-10, and reacting for 2h at room temperature. After the reaction, the mixture was extracted with 40mL of dichloromethane, the organic layer was washed with water (2X 30mL), the organic layer was washed with a saturated sodium chloride solution (1X 40mL), dried over anhydrous magnesium sulfate, and a portion of the solvent was evaporated under reduced pressure to crystallize out, whereby 1.39g of the product was obtained, the yield was 68.9%, and the melting point of the product was: 155 to 157 ℃.
Example 9
This example illustrates the preparation of 5- (((4-chlorophenyl) furan-2-methylene) amino) -1- (4-fluorophenyl) -1H-pyrazole-3-carbonitrile in a 100mL four-necked flask, 0.01mol of 5-amino-1- (4-fluorophenyl) -3-cyano-1H-pyrazole, 40mL of toluene and 5 drops of piperidine were added, stirred to dissolve it, placed in a condenser and Dean-Stark trap under reflux, and 5.5mmol of 5- (4-chlorophenyl) furan-2-carbaldehyde in toluene was added dropwise thereto, and reacted for 2H. After the reaction is finished, most of toluene is removed by reduced pressure rotary evaporation, and the crude product is obtained by cooling crystallization and filtration. The crude product was recrystallized from 5mL of toluene to give the final product in 88% yield. Melting point of the product: 209-211 ℃.
Example 10
This example illustrates the preparation of diethyl (5- (4-chlorophenyl) furan-2-methylidene) ((3-cyano-1- (4-fluorophenyl) -1H-pyrazol-5-yl) amino) phosphonate
A50 mL four-necked flask was charged with 0.002mol of 5- (((4-chlorophenyl) furan-2-methylene) amino) -1- (4-fluorophenyl) -1H-pyrazole-3-carbonitrile and 5mL of diethyl phosphite, and the reaction was stirred at 80 ℃. After the reaction, the excessive diethyl phosphite is removed by reduced pressure rotary evaporation to obtain a crude product. The crude product was recrystallized from 3mL of methanol to give a white solid, 0.66g of final product, 62.5% yield. Melting point of the product: 130-131 ℃;1H NMR(CDCl3，δ)：δ7.51(ddd，J＝9.0，7.9，5.8Hz，4H，phenyl-H)，7.36(d，J＝8.6Hz，2H，phenyl-H)，7.22(t，J＝8.5Hz，2H，phenyl-H)，6.62(d，J＝3.4Hz，1H，furan-H)，6.49(t，J＝3.2Hz，1H，furan-H)，5.95(s，1H，pyrazole-H)，4.68(s，1H，-NH-)，4.62(s，1H，P-CH)，4.17(m，2H，-CH2-)，4.06(m，1H，-CH2-)，3.91(ddd，J＝11.4，10.1，7.1Hz，1H，-CH2-)，1.33(t，J＝7.1Hz，3H，-CH3)，1.18(t，J＝7.1Hz，3H，-CH3).
example 11
This example illustrates the preparation of 5-amino-1- (4-chlorophenyl) -3-cyano-1H-pyrazole
A250 mL round-bottom three-necked flask was charged with 0.01mol of 4-chloroaniline and a small amount of ethanol, and 3.0mL (0.035mol) of concentrated hydrochloric acid was added dropwise with stirring under ice-bath conditions. 0.018mol of sodium nitrite is dissolved in 10mL of water, slowly dropped into the flask, and reacted for 0.5h after the dropping is finished to obtain yellow diazonium salt solution.
Adding 0.01mol of 2, 3-dicyanopropionic acid ethyl ester into a three-neck flask, and dripping the prepared diazonium salt solution into the flask to finish the reaction for 2 hours. Adding ammonia water, adjusting the pH value to 9-10, and reacting for 2h at room temperature. After the reaction, the mixture was extracted with 40mL of dichloromethane, the organic layer was washed with water (2X 30mL), the organic layer was washed with a saturated sodium chloride solution (1X 40mL), dried over anhydrous magnesium sulfate, and a portion of the solvent was evaporated under reduced pressure to crystallize out, whereby 1.83g of a product was obtained, the yield was 83.6%, and the melting point of the product was: 180-181 ℃.
Example 12
This example illustrates the preparation of 5- (((4-chlorophenyl) furan-2-methylene) amino) -1- (4-chlorophenyl) -1H-pyrazole-3-carbonitrile in a 100mL four-necked flask, 0.01mol of 5-amino-1- (4-chlorophenyl) -3-cyano-1H-pyrazole, 40mL of toluene and 5 drops of piperidine were added, stirred to dissolve it, placed in a condenser and Dean-Stark trap under reflux, and a toluene solution containing 5.5mmol of 5- (4-chlorophenyl) furan-2-carbaldehyde was added dropwise thereto, and reacted for 2H. After the reaction is finished, most of toluene is removed by reduced pressure rotary evaporation, and the crude product is obtained by cooling crystallization and filtration. The crude product was recrystallized from 5mL of toluene to give the final product in 92% yield. Melting point of the product: 197-199 ℃.
Example 13
This example illustrates the preparation of diethyl (5- (4-chlorophenyl) furan-2-methylidene) ((3-cyano-1- (4-chlorophenyl) -1H-pyrazol-5-yl) amino) phosphonate
A50 mL four-necked flask was charged with 0.002mol of 5- (((4-chlorophenyl) furan-2-methylene) amino) -1- (4-chlorophenyl) -1H-pyrazole-3-carbonitrile and 5mL of diethyl phosphite, and the reaction was stirred at 80 ℃. After the reaction, the excessive diethyl phosphite is removed by reduced pressure rotary evaporation to obtain a crude product. The crude product was recrystallized from 3mL of methanol to give a white solid, 0.67g of final product, 61.4% yield. Melting point of the product: 152-153 ℃;1H NMR(CDCl3，δ)：δ7.47(m，8H，phenyl-H)，6.56(dd，J＝52.8，3.3Hz，2H，furan-H)，5.95(s，1H，pyrazole-H)，4.68(dd，J＝27.3，19.3Hz，1H，-NH-)，4.17(d，J＝7.7Hz，1H，P-CH)，1.64(s，4H，-CH2-)，1.34(t，J＝7.1Hz，3H，-CH3)，1.18(t，J＝7.1Hz，3H，-CH3).
example 14
This example illustrates the preparation of 5-amino-1- (4-bromophenyl) -3-cyano-1H-pyrazole
A250 mL round-bottom three-neck flask was charged with 0.01mol of 4-bromoaniline and a small amount of ethanol, and 3.0mL (0.035mol) of concentrated hydrochloric acid was added dropwise with stirring under ice bath. 0.018mol of sodium nitrite is dissolved in 10mL of water, slowly dropped into the flask, and reacted for 0.5h after the dropping is finished to obtain yellow diazonium salt solution.
Adding 0.01mol of 2, 3-dicyanopropionic acid ethyl ester into a three-neck flask, and dripping the prepared diazonium salt solution into the flask to finish the reaction for 2 hours. Adding ammonia water, adjusting the pH value to 9-10, and reacting for 2h at room temperature. After the reaction, the mixture was extracted with 40mL of dichloromethane, the organic layer was washed with water (2X 30mL), the organic layer was washed with a saturated sodium chloride solution (1X 40mL), dried over anhydrous magnesium sulfate, and a portion of the solvent was evaporated under reduced pressure to crystallize out, whereby 2.11g of the product was obtained, the yield was 80.3%, and the melting point of the product was: 188-190 ℃.
Example 15
This example illustrates the preparation of 5- (((4-chlorophenyl) furan-2-methylene) amino) -1- (4-bromophenyl) -1H-pyrazole-3-carbonitrile into a 100mL four-necked flask, 0.01mol of 5-amino-1- (4-bromophenyl) -3-cyano-1H-pyrazole, 40mL of toluene, and 5 drops of piperidine were added, dissolved by stirring, placed in a condenser and Dean-Stark trap under reflux, and a toluene solution containing 5.5mmol of 5- (4-chlorophenyl) furan-2-carbaldehyde was added dropwise, and reacted for 2 hours. After the reaction is finished, most of toluene is removed by reduced pressure rotary evaporation, and the crude product is obtained by cooling crystallization and filtration. The crude product was recrystallized from 5mL of toluene to give the final product in 89% yield. Melting point of the product: 180-182 ℃.
Example 16
This example illustrates the preparation of diethyl (5- (4-chlorophenyl) furan-2-methylidene) ((3-cyano-1- (4-bromophenyl) -1H-pyrazol-5-yl) amino) phosphonate
A50 mL four-necked flask was charged with 0.002mol of 5- (((4-chlorophenyl) furan-2-methylene) amino) -1- (4-bromophenyl) -1H-pyrazole-3-carbonitrile and 5mL of diethyl phosphite, and the reaction was stirred at 80 ℃. After the reaction, the excessive diethyl phosphite is removed by reduced pressure rotary evaporation to obtain a crude product. The crude product was recrystallized from 3mL of methanol to give a white solid, 0.79g of final product, 67.1% yield. Melting point of the product: 120-121 ℃;1H NMR(CDCl3，δ)：δ7.80(d，J＝8.6Hz，2H，phenyl-H)，7.74(d，J＝8.4Hz，2H，phenyl-H)，7.54(d，J＝8.5Hz，2H，phenyl-H)，7.36(d，J＝8.5Hz，2H，phenyl-H)，6.62(d，J＝3.4Hz，1H，furan-H)，6.50(t，J＝3.2Hz，1H，furan-H)，5.98(s，1H，pyrazole-H)，4.68(s，1H，-NH-)，4.63(s，1H，P-CH)，4.18(m，2H，-CH2-)，4.07(m，1H，-CH2-)，3.91(dd，J＝16.5，9.2Hz，1H，-CH2-)，1.34(t，J＝7.1Hz，3H，-CH3)，1.18(t，J＝7.1Hz，3H，-CH3).
example 17
This example illustrates the preparation of 5-amino-1- (3-bromophenyl) -3-cyano-1H-pyrazole
A250 mL round-bottom three-neck flask was charged with 0.01mol of 3-bromoaniline and a small amount of ethanol, and 3.0mL (0.035mol) of concentrated hydrochloric acid was added dropwise with stirring under ice bath. 0.018mol of sodium nitrite is dissolved in 10mL of water, slowly dropped into the flask, and reacted for 0.5h after the dropping is finished to obtain yellow diazonium salt solution.
Adding 0.01mol of 2, 3-dicyanopropionic acid ethyl ester into a three-neck flask, and dripping the prepared diazonium salt solution into the flask to finish the reaction for 2 hours. Adding ammonia water, adjusting the pH value to 9-10, and reacting for 2h at room temperature. After the reaction, the mixture was extracted with 40mL of dichloromethane, the organic layer was washed with water (2X 30mL), the organic layer was washed with a saturated sodium chloride solution (1X 40mL), dried over anhydrous magnesium sulfate, and a portion of the solvent was evaporated under reduced pressure to crystallize out, whereby 1.84g of the product was obtained, the yield was 70.1%, and the melting point of the product was: 182 to 184 ℃.
Example 18
This example illustrates the preparation of 5- (((4-chlorophenyl) furan-2-methylene) amino) -1- (3-bromophenyl) -1H-pyrazole-3-carbonitrile
In a 100mL four-necked flask, 0.01mol of 5-amino-1- (3-bromophenyl) -3-cyano-1H-pyrazole, 40mL of toluene and 5 drops of piperidine were added, and the mixture was dissolved by stirring, and then, a condenser tube and a Dean-Stark trap were placed to reflux the mixture in water, and a toluene solution in which 5.5mmol of 5- (4-chlorophenyl) furan-2-carbaldehyde was dissolved was added dropwise to the mixture, followed by reaction for 2 hours. After the reaction is finished, most of toluene is removed by reduced pressure rotary evaporation, and the crude product is obtained by cooling crystallization and filtration. The crude product was recrystallized from 5mL of toluene to give the final product in 82% yield. Melting point of the product: 177-179 ℃.
Example 19
This example illustrates the preparation of diethyl (5- (4-chlorophenyl) furan-2-methylidene) ((3-cyano-1- (3-bromophenyl) -1H-pyrazol-5-yl) amino) phosphonate
A50 mL four-necked flask was charged with 0.002mol of 5- (((4-chlorophenyl) furan-2-methylene) amino) -1- (3-bromophenyl) -1H-pyrazole-3-carbonitrile and 5mL of diethyl phosphite, and the reaction was stirred at 80 ℃. After the reaction, the excessive diethyl phosphite is removed by reduced pressure rotary evaporation to obtain a crude product. The crude product was recrystallized from 3mL of methanol to give a white solid, 0.68g of final product, 57.8% yield. Product produced by birthMelting point of the product: 150-151 ℃;1H NMR(CDCl3，δ)：δ7.66(d，J＝8.1Hz，2H，phenyl-H)，7.54(d，J＝8.5Hz，2H，phenyl-H)，7.43(d，J＝8.5Hz，2H，phenyl-H)，7.37(d，J＝8.0Hz，2H，phenyl-H)，6.62(d，J＝2.7Hz，1H，furan-H)，6.49(t，1H，furan-H)，5.95(s，1H，pyrazole-H)，4.75(dd，J＝8.9，5.3Hz，1H，-NH-)，4.64(dd，J＝22.8，8.6Hz，1H，P-CH)，4.18(m，2H，-CH2-)，4.06(dd，J＝13.1，5.2Hz，1H，-CH2-)，3.90(dd，J＝16.9，8.5Hz，1H，-CH2-)，1.34(t，J＝7.1Hz，3H，-CH3)，1.18(t，J＝7.1Hz，3H，-CH3).
example 20
This example illustrates the preparation of 5-amino-1-phenyl-3-cyano-1H-pyrazole
0.01mol of aniline and a small amount of ethanol were added to a 250mL round-bottom three-necked flask, and 3.0mL (0.035mol) of concentrated hydrochloric acid was added dropwise with stirring under ice-bath conditions. 0.018mol of sodium nitrite is dissolved in 10mL of water, slowly dropped into the flask, and reacted for 0.5h after the dropping is finished to obtain yellow diazonium salt solution.
Adding 0.01mol of 2, 3-dicyanopropionic acid ethyl ester into a three-neck flask, and dripping the prepared diazonium salt solution into the flask to finish the reaction for 2 hours. Adding ammonia water, adjusting the pH value to 9-10, and reacting for 2h at room temperature. After the reaction, the mixture was extracted with 40mL of dichloromethane, the organic layer was washed with water (2X 30mL), the saturated sodium chloride solution was washed (1X 40mL), dried over anhydrous magnesium sulfate, and a portion of the solvent was evaporated under reduced pressure to crystallize out, whereby 1.12g of the product was obtained, the yield was 60.9%, and the melting point of the product was: 122 to 124 ℃.
Example 21
This example illustrates the preparation of 5- (((4-chlorophenyl) furan-2-methylene) amino) -1-phenyl-1H-pyrazole-3-carbonitrile
In a 100mL four-necked flask, 0.01mol of 5-amino-1-phenyl-3-cyano-1H-pyrazole, 40mL of toluene and 5 drops of piperidine were added, stirred to dissolve, equipped with a condenser tube and a Dean-Stark trap and refluxed with water, and a toluene solution containing 5.5mmol of 5- (4-chlorophenyl) furan-2-carbaldehyde was added dropwise and reacted for 2 hours. After the reaction is finished, most of toluene is removed by reduced pressure rotary evaporation, and the crude product is obtained by cooling crystallization and filtration. The crude product was recrystallized from 5mL of toluene to give the final product in 87% yield. Melting point of the product: 138-140 ℃.
Example 22
This example illustrates the preparation of diethyl (5- (4-chlorophenyl) furan-2-methylidene) ((3-cyano-1-phenyl-1H-pyrazol-5-yl) amino) phosphonate
A50 mL four-necked flask was charged with 0.002mol of 5- (((4-chlorophenyl) furan-2-methylene) amino) -1-phenyl-1H-pyrazole-3-carbonitrile and 5mL of diethyl phosphite, and the reaction was stirred at 80 ℃. After the reaction, the excessive diethyl phosphite is removed by reduced pressure rotary evaporation to obtain a crude product. The crude product was recrystallized from 3mL of methanol to give a white solid, 0.68g of final product, 66.7% yield. Melting point of the product: 137-138 ℃;1H NMR(CDCl3，δ)：δ7.51(m，7H，phenyl-H)，7.35(d，J＝8.5Hz，2H，phenyl-H)，6.62(d，J＝3.1Hz，1H，furan-H)，6.48(t，J＝2.9Hz，1H，furan-H)，5.95(s，1H，pyrazole-H)，4.79(m，1H，-NH-)，4.67(dd，J＝22.4，8.7Hz，1H，P-CH)，4.17(m，2H，-CH2-)，4.07(dt，J＝10.0，7.3Hz，1H，-CH2-)，3.92(m，1H，-CH2-)，1.32(t，J＝7.0Hz，3H，-CH3)，1.18(t，J＝7.0Hz，3H，-CH3).
example 23
This example illustrates the preparation of 5-amino-1- (4-methylphenyl) -3-cyano-1H-pyrazole
To a 250mL round-bottom three-necked flask, 0.01mol of 4-methylaniline and a small amount of ethanol were added, and 3.0mL (0.035mol) of concentrated hydrochloric acid was added dropwise with stirring under ice-bath conditions. 0.018mol of sodium nitrite is dissolved in 10mL of water, slowly dropped into the flask, and reacted for 0.5h after the dropping is finished to obtain yellow diazonium salt solution.
Adding 0.01mol of 2, 3-dicyanopropionic acid ethyl ester into a three-neck flask, and dripping the prepared diazonium salt solution into the flask to finish the reaction for 2 hours. Adding ammonia water, adjusting the pH value to 9-10, and reacting for 2h at room temperature. After the reaction, the mixture was extracted with 40mL of dichloromethane, the organic layer was washed with water (2X 30mL), the organic layer was washed with a saturated sodium chloride solution (1X 40mL), dried over anhydrous magnesium sulfate, and a portion of the solvent was evaporated under reduced pressure to crystallize out, whereby 1.55g of the product was obtained, the yield was 78.2%, and the melting point of the product was: 120 to 121 ℃.
Example 24
This example illustrates the preparation of 5- (((4-chlorophenyl) furan-2-methylene) amino) -1- (4-methylphenyl) -1H-pyrazole-3-carbonitrile
In a 100mL four-necked flask, 0.01mol of 5-amino-1- (4-methylphenyl) -3-cyano-1H-pyrazole, 40mL of toluene and 5 drops of piperidine were added, and the mixture was dissolved by stirring, then a condenser tube and a Dean-Stark trap were placed to reflux the mixture under water distribution, and a toluene solution containing 5.5mmol of 5- (4-chlorophenyl) furan-2-carbaldehyde was added dropwise and reacted for 2 hours. After the reaction is finished, most of toluene is removed by reduced pressure rotary evaporation, and the crude product is obtained by cooling crystallization and filtration. The crude product was recrystallized from 5mL of toluene to give the final product in 80% yield. Melting point of the product: 150-152 ℃.
Example 25
This example illustrates the preparation of diethyl (5- (4-chlorophenyl) furan-2-methylidene) ((3-cyano-1- (4-methylphenyl) -1H-pyrazol-5-yl) amino) phosphonate
A50 mL four-necked flask was charged with 0.002mol of 5- (((4-chlorophenyl) furan-2-methylene) amino) -1- (4-methylphenyl) -1H-pyrazole-3-carbonitrile and 5mL of diethyl phosphite, and the reaction was stirred at 80 ℃. After the reaction, the excessive diethyl phosphite is removed by reduced pressure rotary evaporation to obtain a crude product. The crude product was recrystallized from 3mL of methanol to give a white solid, 0.67g of final product, 63.8% yield. Melting point of the product: 140-141 ℃;1H NMR(CDCl3，δ)：δ7.53(d，J＝8.6Hz，2H，phenyl-H)，7.34(m，6H，phenyl-H)，6.61(d，J＝3.3Hz，1H，furan-H)，6.47(t，J＝3.2Hz，1H，furan-H)，5.93(s，1H，pyrazole-H)，4.69(s，1H，-NH-)，4.63(s，1H，P-CH)，4.17(m，2H，-CH2-)，4.05(m，1H，-CH2-)，3.91(m，1H，-CH2-)，2.43(s，3H，-CH3)，1.32(t，J＝7.1Hz，3H，-CH3)，1.18(t，J＝7.0Hz，3H，-CH3).
example 26
This example illustrates the preparation of 5-amino-1- (4-methoxyphenyl) -3-cyano-1H-pyrazole
A250 mL round-bottom three-necked flask was charged with 0.01mol of 4-methoxyaniline and a small amount of ethanol, and 3.0mL (0.035mol) of concentrated hydrochloric acid was added dropwise with stirring under ice-bath conditions. 0.018mol of sodium nitrite is dissolved in 10mL of water, slowly dropped into the flask, and reacted for 0.5h after the dropping is finished to obtain yellow diazonium salt solution.
Adding 0.01mol of 2, 3-dicyanopropionic acid ethyl ester into a three-neck flask, and dripping the prepared diazonium salt solution into the flask to finish the reaction for 2 hours. Adding ammonia water, adjusting the pH value to 9-10, and reacting for 2h at room temperature. After the reaction, the mixture was extracted with 40mL of dichloromethane, the organic layer was washed with water (2X 30mL), the organic layer was washed with a saturated sodium chloride solution (1X 40mL), dried over anhydrous magnesium sulfate, and a portion of the solvent was evaporated under reduced pressure to crystallize, whereby 0.92g of the product was obtained, the yield was 42.7%, and the melting point of the product was: 110 to 112 ℃.
Example 27
This example illustrates the preparation of 5- (((4-chlorophenyl) furan-2-methylene) amino) -1- (4-methoxyphenyl) -1H-pyrazole-3-carbonitrile
In a 100mL four-necked flask, 0.01mol of 5-amino-1- (4-methoxyphenyl) -3-cyano-1H-pyrazole, 40mL of toluene and 5 drops of piperidine were added, and the mixture was dissolved by stirring, and then, a condenser tube and a Dean-Stark trap were placed to reflux the mixture under water distribution, and a toluene solution in which 5.5mmol of 5- (4-chlorophenyl) furan-2-carbaldehyde was dissolved was added dropwise to the mixture, followed by reaction for 2 hours. After the reaction is finished, most of toluene is removed by reduced pressure rotary evaporation, and the crude product is obtained by cooling crystallization and filtration. The crude product was recrystallized from 5mL of toluene to give the final product in 78% yield. Melting point of the product: 163 to 165 ℃.
Example 28
This example illustrates the preparation of diethyl (5- (4-chlorophenyl) furan-2-methylidene) ((3-cyano-1- (4-methoxyphenyl) -1H-pyrazol-5-yl) amino) phosphonate
A50 mL four-necked flask was charged with 0.002mol of 5- (((4-chlorophenyl) furan-2-methylene) amino) -1- (4-methoxyphenyl) -1H-pyrazole-3-carbonitrile and 5mL of diethyl phosphite, and the reaction was stirred at 80 ℃. After the reaction, the excessive diethyl phosphite is removed by reduced pressure rotary evaporation to obtain a crude product. The crude product was recrystallized from 3mL of methanol to give a white solid, 0.63g of final product, 57.9% yield. Melting point of the product: 120-121 ℃;1H NMR(CDCl3，δ)：δ7.53(d，J＝8.3Hz，2H，phenyl-H)，7.37(dd，J＝13.2，8.6Hz，4H，phenyl-H)，7.01(d，J＝8.7Hz，2H，phenyl-H)，6.61(d，J＝3.1Hz，1H，furan-H)，6.47(d，J＝2.9Hz，1H，furan-H)，5.92(s，1H，pyrazole-H)，4.67(s，1H，-NH-)，4.62(d，J＝7.7Hz，1H，P-CH)，4.16(dt，J＝14.8，7.2Hz，2H，-CH2-)，4.05(dt，J＝21.7，7.3Hz，1H，-CH2-)，3.93(dd，J＝15.7，7.6Hz，1H，-CH2-)，3.86(s，3H，-OCH3)，1.32(t，J＝7.0Hz，3H，-CH3)，1.18(t，J＝7.0Hz，3H，-CH3).
example 29
This example illustrates the preparation of 5-amino-1- (4-trifluoromethylphenyl) -3-cyano-1H-pyrazole
To a 250mL round-bottom three-necked flask, 0.01mol of 4-trifluoromethylaniline and a small amount of ethanol were added, and 3.0mL (0.035mol) of concentrated hydrochloric acid was added dropwise with stirring under ice-bath conditions. 0.018mol of sodium nitrite is dissolved in 10mL of water, slowly dropped into the flask, and reacted for 0.5h after the dropping is finished to obtain yellow diazonium salt solution.
Adding 0.01mol of 2, 3-dicyanopropionic acid ethyl ester into a three-neck flask, and dripping the prepared diazonium salt solution into the flask to finish the reaction for 2 hours. Adding ammonia water, adjusting the pH value to 9-10, and reacting for 2h at room temperature. After the reaction, the mixture was extracted with 40mL of dichloromethane, the organic layer was washed with water (2X 30mL), the organic layer was washed with a saturated sodium chloride solution (1X 40mL), dried over anhydrous magnesium sulfate, and a portion of the solvent was evaporated under reduced pressure to crystallize out, whereby 1.49g of the product was obtained, the yield was 58.9%, and the melting point of the product was: 168-170 ℃.
Example 30
This example illustrates the preparation of 5- (((4-chlorophenyl) furan-2-methylene) amino) -1- (4-trifluoromethylphenyl) -1H-pyrazole-3-carbonitrile
In a 100mL four-necked flask, 0.01mol of 5-amino-1- (4-trifluoromethylphenyl) -3-cyano-1H-pyrazole, 40mL of toluene and 5 drops of piperidine were added, and the mixture was dissolved by stirring, and then, a condenser tube and a Dean-Stark trap were placed to reflux the mixture in water, and a toluene solution in which 5.5mmol of 5- (4-chlorophenyl) furan-2-carbaldehyde was dissolved was added dropwise to the mixture, followed by reaction for 2 hours. After the reaction is finished, most of toluene is removed by reduced pressure rotary evaporation, and the crude product is obtained by cooling crystallization and filtration. The crude product was recrystallized from 5mL of toluene to give the final product in 82% yield. Melting point of the product: 187-189 ℃.
Example 31
This example illustrates the preparation of diethyl (5- (4-chlorophenyl) furan-2-methylidene) ((3-cyano-1- (4-trifluoromethylphenyl) -1H-pyrazol-5-yl) amino) phosphonate
A50 mL four-necked flask was charged with 0.002mol of 5- (((4-chlorophenyl) furan-2-methylene) amino) -1- (4-trifluoromethylphenyl) -1H-pyrazole-3-carbonitrile and 5mL of diethyl phosphite, and the reaction was stirred at 80 ℃. After the reaction, the excessive diethyl phosphite is removed by reduced pressure rotary evaporation to obtain a crude product. The crude product was recrystallized from 3mL of methanol to give a white solid, 0.64g of final product, 55.6% yield. Melting point of the product: 167-169 ℃;1H NMR(CDCl3，δ)：δ7.77(dd，J＝25.7，8.1Hz，4H，phenyl-H)，7.54(d，J＝8.2Hz，2H，phenyl-H)，7.36(d，J＝8.0Hz，2H，phenyl-H)，6.63(s，1H，furan-H)，6.50(s，1H，furan-H)，5.98(s，1H，pyrazole-H)，4.84(s，1H，-NH-)，4.66(dd，J＝22.4，7.4Hz，1H，P-CH)，4.18(dd，J＝14.4，7.2Hz，2H，-CH2-)，4.07(dd，J＝16.8，7.2Hz，1H，-CH2-)，3.91(dd，J＝15.8，8.4Hz，1H，-CH2-)，1.34(t，J＝6.9Hz，3H，-CH3)，1.18(t，J＝6.8Hz，3H，-CH3).
example 32
This example illustrates the preparation of 5-amino-1- (2, 4-difluorophenyl) -3-cyano-1H-pyrazole
A250 mL round-bottom three-necked flask was charged with 0.01mol of 2, 4-difluoroaniline and a small amount of ethanol, and 3.0mL (0.035mol) of concentrated hydrochloric acid was added dropwise with stirring under ice-bath conditions. 0.018mol of sodium nitrite is dissolved in 10mL of water, slowly dropped into the flask, and reacted for 0.5h after the dropping is finished to obtain yellow diazonium salt solution.
Adding 0.01mol of 2, 3-dicyanopropionic acid ethyl ester into a three-neck flask, and dripping the prepared diazonium salt solution into the flask to finish the reaction for 2 hours. Adding ammonia water, adjusting the pH value to 9-10, and reacting for 2h at room temperature. After the reaction, the mixture was extracted with 40mL of dichloromethane, the organic layer was washed with water (2X 30mL), the organic layer was washed with a saturated sodium chloride solution (1X 40mL), dried over anhydrous magnesium sulfate, and a portion of the solvent was evaporated under reduced pressure to crystallize out, whereby 1.02g of the product was obtained, the yield was 46.5%, and the melting point of the product was: 155 to 157 ℃.
Example 33
This example illustrates the preparation of 5- (((4-chlorophenyl) furan-2-methylene) amino) -1- (2, 4-difluorophenyl) -1H-pyrazole-3-carbonitrile
In a 100mL four-necked flask, 0.01mol of 5-amino-1- (2, 4-difluorophenyl) -3-cyano-1H-pyrazole, 40mL of toluene and 5 drops of piperidine were added, and the mixture was dissolved by stirring, and then a condenser tube and a Dean-Stark trap were placed under reflux, and a toluene solution in which 5.5mmol of 5- (4-chlorophenyl) furan-2-carbaldehyde was dissolved was added dropwise to react for 2 hours. After the reaction is finished, most of toluene is removed by reduced pressure rotary evaporation, and the crude product is obtained by cooling crystallization and filtration. The crude product was recrystallized from 5mL of toluene to give the final product in 84% yield. Melting point of the product: 195-197 deg.c.
Example 34
This example illustrates the preparation of diethyl (5- (4-chlorophenyl) furan-2-methylidene) ((3-cyano-1- (2, 4-, difluorophenyl) -1H-pyrazol-5-yl) amino) phosphonate
A50 mL four-necked flask was charged with 0.002mol of 5- (((4-chlorophenyl) furan-2-methylene) amino) -1- (2, 4-difluorophenyl) -1H-pyrazole-3-carbonitrile and 5mL of diethyl phosphite, and the reaction was stirred at 80 ℃. After the reaction, the excessive diethyl phosphite is removed by reduced pressure rotary evaporation to obtain a crude product. The crude product was recrystallized from 3mL of methanol to give a white solid, 0.55g of final product, 50.3% yield. Melting point of the product: 120-121 ℃;1H NMR(CDCl3，δ)：δ7.55(d，J＝8.4Hz，2H，phenyl-H)，7.46(dd，J＝14.0，8.2Hz，1H，phenyl-H)，7.36(d，J＝8.4Hz，2H，phenyl-H)，7.06(t，J＝8.1Hz，2H，phenyl-H)，6.62(d，J＝2.9Hz，1H，furan-H)，6.49(s，1H，furan-H)，5.92(s，1H，pyrazole-H)，4.65(dd，J＝22.5，8.5Hz，1H，-NH-)，4.56(m，1H，P-CH)，4.14(m，2H，-CH2-)，4.04(dt，J＝21.4，7.1Hz，1H，-CH2-)，3.90(dt，J＝16.9Hz，8.3Hz，1H，-CH2-)，1.30(t，J＝7.0Hz，3H，-CH3)，1.17(t，J＝7.0Hz，3H，-CH3).
example 35
This example illustrates the preparation of 5-amino-1- (2, 3, 4-trifluorophenyl) -3-cyano-1H-pyrazole
A250 mL round-bottom three-neck flask was charged with 0.01mol of 2, 3, 4-trifluoroaniline and a small amount of ethanol, and then 3.0mL (0.035mol) of concentrated hydrochloric acid was added dropwise with stirring under ice-bath conditions. 0.018mol of sodium nitrite is dissolved in 10mL of water, slowly dropped into the flask, and reacted for 0.5h after the dropping is finished to obtain yellow diazonium salt solution.
Adding 0.01mol of 2, 3-dicyanopropionic acid ethyl ester into a three-neck flask, and dripping the prepared diazonium salt solution into the flask to finish the reaction for 2 hours. Adding ammonia water, adjusting the pH value to 9-10, and reacting for 2h at room temperature. After the reaction, the mixture was extracted with 40mL of dichloromethane, the organic layer was washed with water (2X 30mL), the organic layer was washed with a saturated sodium chloride solution (1X 40mL), dried over anhydrous magnesium sulfate, and a portion of the solvent was evaporated under reduced pressure to crystallize out, whereby 0.88g of the product was obtained, the yield was 36.8%, and the melting point of the product was: 129-131 ℃.
Example 36
This example illustrates the preparation of 5- (((4-chlorophenyl) furan-2-methylene) amino) -1- (2, 3, 4-trifluorophenyl) -1H-pyrazole-3-carbonitrile
In a 100mL four-necked flask, 0.01mol of 5-amino-1- (2, 3, 4-trifluorophenyl) -3-cyano-1H-pyrazole, 40mL of toluene and 5 drops of piperidine were added, and the mixture was dissolved by stirring, and then a condenser tube and a Dean-Stark trap were placed to reflux water, and a toluene solution containing 5.5mmol of 5- (4-chlorophenyl) furan-2-carbaldehyde was added dropwise to the mixture to conduct a reaction for 2 hours. After the reaction is finished, most of toluene is removed by reduced pressure rotary evaporation, and the crude product is obtained by cooling crystallization and filtration. The crude product was recrystallized from 5mL of toluene to give the final product in 80% yield. Melting point of the product: 182 to 184 ℃.
Example 37
This example illustrates the preparation of diethyl (5- (4-chlorophenyl) furan-2-methylidene) ((3-cyano-1- (2, 3, 4-trifluorophenyl) -1H-pyrazol-5-yl) amino) phosphonate
A50 mL four-necked flask was charged with 0.002mol of 5- (((4-chlorophenyl) furan-2-methylene) amino) -1- (2, 3, 4-trifluorophenyl) -1H-pyrazole-3-carbonitrile and 5mL of diethyl phosphite, and the reaction was stirred at 80 ℃. After the reaction, the excessive diethyl phosphite is removed by reduced pressure rotary evaporation to obtain a crude product. The crude product was recrystallized from 3mL of methanol to give a white solid, most preferably0.69g of final product, yield 60.9%. Melting point of the product: 134-135 ℃;1H NMR(CDCl3，δ)：δ7.55(d，J＝8.4Hz，2H，phenyl-H)，7.36(d，J＝8.5Hz，2H，phenyl-H)，7.24(m，1H，phenyl-H)，7.16(m，J＝16.5，4.4Hz，1H，phenyl-H)，6.63(d，J＝33Hz，1H，furan-H)，6.50(t，J＝3.1Hz，1H，furan-H)，5.94(s，1H，pyrazole-H)，4.68(s，1H，-NH-)，4.62(s，1H，P-CH)，4.15(m，2H，-CH2-)，4.05(m，1H，-CH2-)，3.90(m，1H，-CH2-)，1.32(t，J＝7.1Hz，3H，-CH3)，1.17(t，J＝7.0Hz，3H，-CH3).
example 38
This example illustrates the preparation of 5-amino-1- (2, 6-dichloro-4-trifluoromethylphenyl) -3-cyano-1H-pyrazole
0.01mol of 2, 6-dichloro-4-trifluoromethylaniline and a small amount of ethanol were added to a 250mL round-bottom three-necked flask, and 3.0mL (0.035mol) of concentrated hydrochloric acid was added dropwise with stirring under ice-bath conditions. 0.018mol of sodium nitrite is dissolved in 10mL of water, slowly dropped into the flask, and reacted for 0.5h after the dropping is finished to obtain yellow diazonium salt solution.
Adding 0.0lmol ethyl 2, 3-dicyanopropionate into a three-neck flask, and dripping the prepared diazonium salt solution into the flask to finish the reaction for 2 hours. Adding ammonia water, adjusting the pH value to 9-10, and reacting for 2h at room temperature. After the reaction, the mixture was extracted with 40mL of dichloromethane, the organic layer was washed with water (2X 30mL), the organic layer was washed with a saturated sodium chloride solution (1X 40mL), dried over anhydrous magnesium sulfate, and a portion of the solvent was evaporated under reduced pressure to crystallize out, whereby 0.72g of the product was obtained, the yield was 22.3%, and the melting point of the product was: 118 to 120 ℃.
Example 39
This example illustrates the preparation of 5- (((4-chlorophenyl) furan-2-methylene) amino) -1- (2, 6-dichloro-4-trifluoromethylphenyl) -1H-pyrazole-3-carbonitrile
In a 100mL four-necked flask, 0.01mol of 5-amino-1- (2, 6-dichloro-4-trifluoromethylphenyl) -3-cyano-1H-pyrazole, 40mL of toluene and 5 drops of piperidine were added, and the mixture was dissolved by stirring, and then a condenser tube and a Dean-Stark trap were attached to reflux water, and a toluene solution in which 5.5mmol of 5- (4-chlorophenyl) furan-2-carbaldehyde was dissolved was added dropwise to the mixture, followed by reaction for 2 hours. After the reaction is finished, most of toluene is removed by reduced pressure rotary evaporation, and the crude product is obtained by cooling crystallization and filtration. The crude product was recrystallized from 5mL of toluene to give the final product in 72% yield. Melting point of the product: 143-145 ℃.
Example 40
This example illustrates the preparation of diethyl (5- (4-chlorophenyl) furan-2-methylidene) ((3-cyano-1- (2, 6-dichloro-4-trifluoromethylphenyl) -1H-pyrazol-5-yl) amino) phosphonate
A50 mL four-necked flask was charged with 0.002mol of 5- (((4-chlorophenyl) furan-2-methylene) amino) -1- (2, 6-dichloro-4-trifluoromethylphenyl) -1H-pyrazole-3-carbonitrile and 5mL of diethyl phosphite, and the reaction was stirred at 80 ℃. After the reaction, the excessive diethyl phosphite is removed by reduced pressure rotary evaporation to obtain a crude product. The crude product was recrystallized from 3mL of methanol to give a white solid, 0.74g of final product, 57.1% yield. Melting point of the product: 126-127 ℃;1H NMR(CDCl3，δ)：δ7.55(d，J＝8.6Hz，2H，phenyl-H)，7.37(d，J＝8.6Hz，2H，phenyl-H)，7.23(m，1H，phenyl-H)，7.15(m，1H，phenyl-H)，6.63(d，J＝3.4Hz，1H，furan-H)，6.50(t，J＝3.2Hz，1H，furan-H)，5.93(s，1H，pyrazole-H)，4.68(s，1H，-NH-)，4.62(s，1H，P-CH)，4.17(ddd，J＝15.7，7.1，1.6Hz，2H，-CH2-)，4.05(ddd，J＝14.4，7.2，2.9Hz，1H，-CH2-)，3.89(m，1H，-CH2-)，1.32(t，J＝7.1Hz，3H，-CH3)，1.17(t，J＝7.1Hz，3H，-CH3).
example 410.1% insecticidal Aerosol
An insecticidal preparation was prepared by mixing together 0.1 part by weight of each compound according to claim 1 of the present invention, and 39.9 parts by weight of D80 mineral spirits at 40 ℃. The resulting formulation was charged into an aerosol can, and 60.0 parts by weight of propane and butane were injected through a valve under pressure to obtain an insecticidal aerosol.
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Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004060305A2 (en) * | 2002-12-31 | 2004-07-22 | Deciphera Pharmaceuticals, Llc | Anti-cancer medicaments |
| CN103130796A (en) * | 2013-01-25 | 2013-06-05 | 青岛科技大学 | 3-tertiary butyl pyrazole amides compounds and application thereof |
| CN103159744A (en) * | 2013-04-08 | 2013-06-19 | 南京工业大学 | Halogen benzene cyano pyrazole compound with insecticidal effect, preparation method and application |
| CN103420975A (en) * | 2013-01-25 | 2013-12-04 | 青岛科技大学 | Fluorine-contained o-amino thiobenzamide type compound and application thereof |
| CN104829538A (en) * | 2015-05-22 | 2015-08-12 | 南京工业大学 | Pyrazole compound containing chrysanthemic acid structure, preparation method and application |
| CN104829537A (en) * | 2015-05-22 | 2015-08-12 | 南京工业大学 | Pyrazole compound containing ureide structure, preparation method and application |
| CN105601632A (en) * | 2016-03-16 | 2016-05-25 | 南京工业大学 | Halogeno-benzene cyano pyrazole compound containing purine structure, preparation method and application thereof |
| CN105712975A (en) * | 2016-01-26 | 2016-06-29 | 西安近代化学研究所 | Pyrazole amide compound containing 1,2,3-triazole ring and application of pyrazole amide compound containing 1,2,3-triazole ring |
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Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004060305A2 (en) * | 2002-12-31 | 2004-07-22 | Deciphera Pharmaceuticals, Llc | Anti-cancer medicaments |
| CN103130796A (en) * | 2013-01-25 | 2013-06-05 | 青岛科技大学 | 3-tertiary butyl pyrazole amides compounds and application thereof |
| CN103420975A (en) * | 2013-01-25 | 2013-12-04 | 青岛科技大学 | Fluorine-contained o-amino thiobenzamide type compound and application thereof |
| CN103159744A (en) * | 2013-04-08 | 2013-06-19 | 南京工业大学 | Halogen benzene cyano pyrazole compound with insecticidal effect, preparation method and application |
| CN104829538A (en) * | 2015-05-22 | 2015-08-12 | 南京工业大学 | Pyrazole compound containing chrysanthemic acid structure, preparation method and application |
| CN104829537A (en) * | 2015-05-22 | 2015-08-12 | 南京工业大学 | Pyrazole compound containing ureide structure, preparation method and application |
| CN105712975A (en) * | 2016-01-26 | 2016-06-29 | 西安近代化学研究所 | Pyrazole amide compound containing 1,2,3-triazole ring and application of pyrazole amide compound containing 1,2,3-triazole ring |
| CN105601632A (en) * | 2016-03-16 | 2016-05-25 | 南京工业大学 | Halogeno-benzene cyano pyrazole compound containing purine structure, preparation method and application thereof |
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