CN110606828A - Trifluoromethyl pyridine amide derivative containing chiral thioether structure and application thereof - Google Patents
Trifluoromethyl pyridine amide derivative containing chiral thioether structure and application thereof Download PDFInfo
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- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
Abstract
The invention discloses a trifluoromethyl pyridine amide compound containing chiral thioether and application thereof, wherein the structure of the trifluoromethyl pyridine amide compound is shown as a general formula I. Wherein the scope of substituents is as defined in the claims. The compound shown in the general formula I has good insecticidal activity and plant virus resistance activity, can be used for preventing and treating pests such as diamondback moth, armyworm, corn borer and the like, and can also be used for preventing and treating plant virus diseases such as TMV and the like.
Description
Technical Field
The invention relates to the field of agricultural chemicals, in particular to a trifluoromethyl pyridine amide derivative containing a chiral thioether structure and application thereof in the aspects of disinsection and antivirus.
Background
In the creation of new green pesticides, fluorine-containing pesticides are the hot field of research by people. Fluorine atoms have the unique properties of electronic effect, hydrogen-like simulation effect, barrier effect and fat-soluble permeation effect, and are increasingly widely applied in the fields of medicinal chemistry, natural product chemistry, pesticide chemistry, fine chemicals and the like (Yang Jichun, et al. pesticide, 2011,4, 289-295). According to incomplete statistics, the fluorine-containing compound in new pesticide varieties developed in recent 10 years reaches more than 50 percent, and the fluorine-containing pesticide has become the main direction of development and application in the pesticide industry (Yang Jichun, et al. pesticide, 2011,4,289 and 295). As an important fluorine-containing heterocyclic structure, the trifluoromethyl pyridine is also a common group in current commercial pesticides, and in registered pesticides, nearly 30 varieties of the pesticides containing the trifluoromethyl pyridine structure, such as sulfoxaflor, flonicamid, pyridalyl, flonicasulfuron, and fluopicolide, all contain the trifluoromethyl pyridine structure. In recent years, compounds having a trifluoromethylpyridine structure have been attracting attention from researchers who have successively disclosed in their patents (e.g., WO,2013191113, WO,2014010737, WO,2014021468, WO,2014119699, JP,2015003906, WO,2015072463, WO,2016024587, CN,104650038, WO,2015177063, WO, 2016023954, etc.) that compounds having a trifluoromethylpyridine structure have excellent insecticidal activity.
The chiral phenomenon is widely existed in nature and commonly exists in pesticide products, and 25-40% of pesticides contain chiral structures, so that the pesticides have different chiral stereoisomers. Although different isomers have similar physicochemical properties, the isomers have significant differences in biological activity, toxicity, absorption, transfer, metabolism and the like, and even have opposite characteristics. Currently, most of the commercialized pesticide varieties containing chiral structures exist in the form of enantiomer mixtures, only one enantiomer plays a role, and the non-effective body and the effective body are applied to fields together, so that risks are brought to human health and ecological environment. The invention adopts the active group splicing principle to splice active substructures such as trifluoromethyl pyridine, ether bond and the like, designs and synthesizes the chiral thioether-containing trifluoromethyl pyridine amide derivatives with novel structures, and has important significance for the research thereof.
Disclosure of Invention
The purpose of the invention is: provides a preparation method and application of trifluoromethyl pyridine amide derivative containing chiral thioether structure, which has better inhibition effect on pathogenic virus and insect pest, and the synthesis method is economic and simple.
A trifluoromethyl pyridine amide compound containing chiral thioether is characterized by having a structure shown as the following general formula:
the general formula is shown as I: represents a chiral carbon atom; r represents C1-C3 alkyl, halogen, haloalkyl, cyano, nitro, alkoxy or alkylthio, or is substituted by more than one; r1Is hydrogen atom, halogen atom, alkyl, C1-C4 alkoxy, C1-C4 alkylthio or C1-C4 sulfonyl; r2Is C1-C5 alkyl.
Further, in the general formula I, the represents chiral carbon atom; r represents methyl, halogen, cyano, nitro, or more than one substituent; r1Hydrogen atom, Cl, Br, F, methyl, C1-C2 alkoxy, C1-C2 alkylthio or C1-C2 sulfonyl; r2Is C1-C3 alkyl.
Further, in the general formula I, the symbol represents a chiral carbon atom; r represents methyl or halogen, or more than one substituent. R1Is Cl, ethylthio or ethylsulfonyl; r2Is C1-C2 alkyl.
More closely, in the context of the present invention, some preferred compounds have the following structure:
1701S: (S) -3-chloro-N- (4-chloro-2-methyl-6- ((1- (methylthio) propan-2-yl) carbamoyl) phenyl) -5- (trifluoromethyl) picolinamide
1701R: (R) -3-chloro-N- (4-chloro-2-methyl-6- ((1- (methylthio) propan-2-yl) carbamoyl) phenyl) -5- (trifluoromethyl) picolinamide
1702S: (S) -3-chloro-N- (2-methyl-6- ((1- (methylthio) propan-2-yl) carbamoyl) phenyl) -5- (trifluoromethyl) picolinamide
1702R: (R) -3-chloro-N- (2-methyl-6- ((1- (methylthio) propan-2-yl) carbamoyl) phenyl) -5- (trifluoromethyl) picolinamide
1703S: (S) -3-chloro-N- (2, 4-difluoro-6- ((1- (methylthio) propan-2-yl) carbamoyl) phenyl) -5- (trifluoromethyl) picolinamide
1703R: (R) -3-chloro-N- (2, 4-difluoro-6- ((1- (methylthio) propan-2-yl) carbamoyl) phenyl) -5- (trifluoromethyl) picolinamide
And S1704: (S) -3-chloro-N- (2, 4-dichloro-6- ((1- (methylthio) propan-2-yl) carbamoyl) phenyl) -5- (trifluoromethyl) picolinamide
1704R: (R) -3-chloro-N- (2, 4-dichloro-6- ((1- (methylthio) propan-2-yl) carbamoyl) phenyl) -5- (trifluoromethyl) picolinamide
1705S: (S) -3-chloro-N- (4-chloro-2- ((1- (methylthio) propan-2-yl) carbamoyl) phenyl) -5- (trifluoromethyl) picolinamide
1705R: (R) -3-chloro-N- (4-chloro-2- ((1- (methylthio) propan-2-yl) carbamoyl) phenyl) -5- (trifluoromethyl) picolinamide
1706S: (S) -N- (4-chloro-2-methyl-6- ((1- (methylthio) propan-2-yl) carbamoyl) phenyl) -3- (ethylsulfanyl) -5- (trifluoromethyl) picolinamide
1706R: (R) -N- (4-chloro-2-methyl-6- ((1- (methylthio) propan-2-yl) carbamoyl) phenyl) -3- (ethylsulfanyl) -5- (trifluoromethyl) picolinamide
1707S: (S) -N- (4-chloro-2-methyl-6- ((1- (methylthio) propan-2-yl) carbamoyl) phenyl) -3- (ethylsulfonyl) -5- (trifluoromethyl) picolinamide
1707R: (R) -N- (4-chloro-2-methyl-6- ((1- (methylthio) propan-2-yl) carbamoyl) phenyl) -3- (ethylsulfonyl) -5- (trifluoromethyl) picolinamide
The above compounds were prepared according to the following scheme. Specific operations can be carried out by referring to the method described in CN 107759518.
1701S to 1705R.
1706S, 1706R.
1707S, 1707R.
Application of chiral thioether-containing trifluoromethyl picolinamide compounds in preparation of antiviral and insect pest resisting medicines.
The chiral thioether trifluoromethyl pyridine amide compound is used in preparing pesticide or pesticide additive for preventing and controlling crop pests and viruses.
The compound is used for preparing pesticides or pesticide additives for preventing and controlling diamondback moth, armyworm and tobacco mosaic virus.
The invention has the beneficial effects that: the invention provides a novel chiral thioether-containing trifluoromethyl pyridine amide compound, and a biological activity test result shows that the compound provided by the invention has a good control effect on pests and also has an excellent control effect on plant virus diseases (TMV). Because fluorine atoms have unique properties such as electronic effect, hydrogen-like simulation effect, fat-soluble permeation effect and the like, the introduction of the trifluoromethyl pyridine group can increase the interaction probability between the compound and a target, thereby improving the activity of the compound. In addition, due to the introduction of a chiral thioether structure, the selectivity of the compound on a target is increased.
Detailed Description
Example 1: 1701S preparation
The first step is as follows:
adding 3-chloro-5-trifluoromethylpyridine acid (1mmol), pyridine (4mmol) and 10ml acetonitrile into a 50ml three-necked flask, stirring under ice salt bath, slowly adding methanesulfonyl chloride (2mmol) with a constant pressure dropping funnel, adding 2-amino-3-methyl-5-chlorobenzoic acid (1.3mmol) once after the dropwise addition is completed, and slowly adding 2-amino-3-methyl-5-chlorobenzoic acid with the constant pressure dropping funnelAdding pyridine (4mmol), adding acetonitrile (5 ml), slowly adding methanesulfonyl chloride (2mmol) with constant pressure dropping funnel after completion of dropwise addition, removing ice bath after completion of dropwise addition, extracting the reaction solution with dichloromethane and water after completion of reaction, mixing the organic layer, and sampling with VPetroleum ether：VEthyl acetatePassing the obtained product through a column at a ratio of 10:1 to obtain trifluoromethyl pyridinoxazone;
the second step is that:
adding trifluoromethyl pyridinoxazone (1mmol) and 10ml acetonitrile, stirring, slowly adding a mixed solution of (S) -1- (methylthio) propan-2-amine (10mmol) and 9ml acetonitrile dropwise through a constant pressure dropping funnel, gradually separating out solids from a clear solution after the dropwise addition is finished, and carrying out suction filtration to obtain the target compound.
1701S physicochemical Properties: light yellow solid, 37.88%, 206-; 1H NMR(400MHz,CDCl3)δ10.07 (s,1H),8.84(d,J＝0.9Hz,1H),8.12(d,J＝1.2Hz,1H),7.55(d,J＝2.3Hz,1H),7.46(d,J＝2.3Hz, 1H),6.52(d,J＝8.1Hz,1H),4.26(dt,J＝14.4,6.4Hz,1H),2.65(tt,J＝13.5,6.7Hz,2H),2.09(s, 3H),1.28(d,J＝6.7Hz,3H). 13C NMR(101MHz,CDCl3)δ165.61,160.85,147.67,143.09(d,J＝3.8 Hz),138.02(d,J＝3.6Hz),136.18,132.96,132.92,132.41,131.14,129.86(d,J＝34.1Hz),126.88, 122.06(d,J＝273.5Hz).45.00,40.41,19.64,16.18. 19FNMR(376MHz,CDCl3)δ -62.57.HRMS(ESI):Calculated for C18H15O2N3Cl3F3S[M+H]+:499.99754,found:499.99658.
example 2: 1701R preparation
The first step is as follows:
adding 3-chloro-5-trifluoromethylpyridine acid (1mmol), pyridine (4mmol) and 10ml acetonitrile into a 50ml three-necked flask, stirring under an ice salt bath, slowly adding methanesulfonyl chloride (2mmol) by using a constant pressure dropping funnel, adding 2-amino-3-methyl-5-chlorobenzoic acid (1.3mmol) once after finishing dropwise addition, slowly adding pyridine (4mmol) by using the constant pressure dropping funnel, adding 5ml acetonitrile, slowly adding methanesulfonyl chloride (2mmol) by using the constant pressure dropping funnel after finishing dropwise addition, removing the ice bath after finishing dropwise addition, and after the reaction is completely finished, removing the ice bathThen, the reaction solution was extracted with dichloromethane and water, and the organic layer was sampled and stirred with VPetroleum ether：VEthyl acetatePassing the obtained product through a column at a ratio of 10:1 to obtain trifluoromethyl pyridinoxazone;
the second step is that:
adding trifluoromethyl pyridinoxazone (1mmol) and 10ml acetonitrile, stirring, slowly adding a mixed solution of (R) -1- (methylthio) propan-2-amine (10mmol) and 9ml acetonitrile dropwise through a constant pressure dropping funnel, gradually separating out solids from a clear solution after the dropwise addition is finished, and carrying out suction filtration to obtain the target compound.
1701R physicochemical properties: pale yellow solid, 64.51%, 229-230 ℃; 1H NMR(400MHz,CDCl3)δ10.25 (s,1H),8.83(d,J＝1.1Hz,1H),8.10(d,J＝1.3Hz,1H),7.36(d,J＝2.0Hz,1H),7.34(d,J＝2.3Hz, 1H),6.32(d,J＝8.1Hz,1H),4.27(dt,J＝14.4,6.3Hz,1H),2.64(d,J＝6.1Hz,2H),2.33(d,J＝2.9 Hz,3H),2.07(s,3H),1.26(d,J＝6.7Hz,3H). 13C NMR(101MHz,CDCl3)δ166.76,160.98,149.08, 143.24(d,J＝3.8Hz),138.36,137.62(d,J＝3.6Hz),133.93,132.73,132.36,132.28,131.50,129.46 (d,J＝34.0Hz),125.03,122.14(d,J＝273.5Hz).44.94,40.53,19.75,19.02,16.30.
19F NMR(376MHz,CDCl3)δ-62.54.HRMS(ESI):Calculated for C19H18O2N3Cl2F3S[M+H]+: 480.05216,found:480.05063.
example 3: 1702S preparation
The first step is as follows:
adding 3-chloro-5-trifluoromethylpyridine acid (1mmol), pyridine (4mmol) and 10ml acetonitrile into a 50ml three-necked bottle, stirring under an ice salt bath, slowly adding methanesulfonyl chloride (2mmol) by using a constant-pressure dropping funnel, adding 2-amino-3-methylbenzoic acid (1.3mmol) at one time after the dropwise addition is finished, slowly adding pyridine (4mmol) by using the constant-pressure dropping funnel, adding 5ml acetonitrile, slowly adding methanesulfonyl chloride (2mmol) by using the constant-pressure dropping funnel after the dropwise addition is finished, removing the ice bath after the dropwise addition is finished, extracting a reaction solution by using dichloromethane and water after the reaction is finished, mixing an organic layer with a sample, and stirring the sample by using VPetroleum ether：VAcetic acidEthyl esterPassing the obtained product through a column at a ratio of 10:1 to obtain trifluoromethyl pyridinoxazone;
the second step is that:
adding trifluoromethyl pyridinoxazone (1mmol) and 10ml acetonitrile, stirring, slowly adding a mixed solution of (S) -1- (methylthio) propan-2-amine (10mmol) and 9ml acetonitrile dropwise through a constant pressure dropping funnel, gradually separating out solids from a clear solution after the dropwise addition is finished, and carrying out suction filtration to obtain the target compound.
1702S physicochemical properties: white solid, 63.72%, 188-; 1H NMR(400MHz,CDCl3)δ10.28(s,1H), 8.77(s,1H),8.02(s,1H),7.39–7.24(m,2H),7.16(t,J＝7.6Hz,1H),4.22(dt,J＝13.1,6.4Hz,1H), 2.59(d,J＝6.0Hz,2H),2.29(s,3H),2.01(s,3H),1.20(d,J＝6.7Hz,3H). 13C NMR 13C NMR(101 MHz,CDCl3)δ168.09,160.92,149.57,143.26(d,J＝3.9Hz),137.50(d,J＝3.6Hz),136.39,133.25, 132.90,132.37,132.23,129.29(d,J＝34.0Hz),126.81,124.95,122.19(d,J＝273.4Hz),44.80,40.62, 19.78,19.10,16.36. 19FNMR(376MHz,CDCl3)δ-62.54.HRMS(ESI):Calculated for C19H19O2N3ClF3S[M+H]+:446.09114,found:446.08990.
example 4: 1702R preparation
The first step is as follows:
adding 3-chloro-5-trifluoromethylpyridine acid (1mmol), pyridine (4mmol) and 10ml acetonitrile into a 50ml three-necked bottle, stirring under an ice salt bath, slowly adding methanesulfonyl chloride (2mmol) by using a constant-pressure dropping funnel, adding 2-amino-3-methylbenzoic acid (1.3mmol) at one time after the dropwise addition is finished, slowly adding pyridine (4mmol) by using the constant-pressure dropping funnel, adding 5ml acetonitrile, slowly adding methanesulfonyl chloride (2mmol) by using the constant-pressure dropping funnel after the dropwise addition is finished, removing the ice bath after the dropwise addition is finished, extracting a reaction solution by using dichloromethane and water after the reaction is finished, mixing an organic layer with a sample, and stirring the sample by using VPetroleum ether：VEthyl acetatePassing the obtained product through a column at a ratio of 10:1 to obtain trifluoromethyl pyridinoxazone;
the second step is that:
adding trifluoromethyl pyridinoxazone (1mmol) and 10ml acetonitrile, stirring, slowly adding a mixed solution of (R) -1- (methylthio) propan-2-amine (10mmol) and 9ml acetonitrile dropwise through a constant pressure dropping funnel, gradually separating out solids from a clear solution after the dropwise addition is finished, and carrying out suction filtration to obtain the target compound.
1702R physicochemical properties: white solid, 67.70%, 188-; 1H NMR(400MHz,CDCl3)δ10.36 (s,1H),8.84(d,J＝1.1Hz,1H),8.10(d,J＝1.3Hz,1H),7.39(d,J＝4.3Hz,1H),7.37(d,J＝4.5Hz, 1H),7.24(t,J＝7.6Hz,1H),6.29(d,J＝8.0Hz,1H),4.30(dt,J＝14.2,6.2Hz,1H),2.66(dd,J＝6.0, 1.0Hz,2H),2.36(s,3H),2.09(s,3H),1.27(d,J＝6.7Hz,3H). 13CNMR(101MHz,CDCl3)δ168.09, 160.92,149.56,143.26(d,J＝3.9Hz),137.50(d,J＝3.5Hz),136.40,133.26,132.90,132.37,132.23, 129.29(d,J＝34.0Hz),126.81,124.95,122.19(d,J＝273.4Hz).44.79,40.62,19.78,19.10,16.36. 19F NMR(376MHz,CDCl3)δ-62.54.HRMS(ESI):Calculated for C19H19O2N3ClF3S[M+H]+: 446.09114,found:446.09027.
example 5: 1703S preparation
The first step is as follows:
adding 3-chloro-5-trifluoromethylpyridine acid (1mmol), pyridine (4mmol) and 10ml acetonitrile into a 50ml three-necked flask, stirring under an ice salt bath, slowly adding methanesulfonyl chloride (2mmol) by using a constant-pressure dropping funnel, adding 2-amino-3, 5-difluorobenzoic acid (1.3mmol) at one time after the completion of dropwise addition, slowly adding pyridine (4mmol) by using the constant-pressure dropping funnel, adding 5ml acetonitrile, slowly adding methanesulfonyl chloride (2mmol) by using the constant-pressure dropping funnel after the completion of dropwise addition, removing the ice bath after the completion of the dropwise addition, extracting a reaction solution by using dichloromethane and water after the completion of the reaction, mixing an organic layer with a sample, and using V to mix the sample by using an organic layerPetroleum ether：VEthyl acetatePassing the obtained product through a column at a ratio of 10:1 to obtain trifluoromethyl pyridinoxazone;
the second step is that:
adding trifluoromethyl pyridinoxazone (1mmol) and 10ml acetonitrile, stirring, slowly adding a mixed solution of (S) -1- (methylthio) propan-2-amine (10mmol) and 9ml acetonitrile dropwise through a constant pressure dropping funnel, gradually separating out solids from a clear solution after the dropwise addition is finished, and carrying out suction filtration to obtain the target compound.
Physicochemical properties of 1703S: white solid, 69.76%, 171-; 1H NMR(400MHz,CDCl3)δ10.26 (s,1H),8.84(d,J＝0.9Hz,1H),8.12(d,J＝1.4Hz,1H),7.13(ddd,J＝7.9,2.6,1.5Hz,1H),7.05 (ddd,J＝10.8,8.3,2.8Hz,1H),6.44(d,J＝8.0Hz,1H),4.30(dt,J＝14.3,6.4Hz,1H),2.67(d,J＝ 6.1Hz,2H),2.09(s,3H),1.29(d,J＝6.7Hz,3H). 13C NMR(101MHz,CDCl3)δ165.30,δ161.72(d, J＝12.3Hz),160.84,159.02(dd,J＝41.6,12.2Hz),156.33,156.21,147.96,143.15(d,J＝3.9Hz), 137.90(d,J＝3.6Hz),134.36(d,J＝9.6Hz),132.83,129.71(d,J＝34.1Hz),122.09(d,J＝273.5 Hz),119.29(dd,J＝14.2,4.1Hz),110.43(dd,J＝23.6,3.6Hz),107.14,106.77(d,J＝25.6Hz).45.01, 40.50,29.72,19.77,16.27. 19F NMR(376MHz,CDCl3)δ-62.57,-109.91,-109.93, -110.10,-110.12.HRMS(ESI):Calculated for C18H15O2N3ClF5S[M+H]+:468.05664,found: 468.05539.
example 6: 1703R preparation
The first step is as follows:
adding 3-chloro-5-trifluoromethylpyridine acid (1mmol), pyridine (4mmol) and 10ml acetonitrile into a 50ml three-necked flask, stirring under an ice salt bath, slowly adding methanesulfonyl chloride (2mmol) by using a constant-pressure dropping funnel, adding 2-amino-3, 5-difluorobenzoic acid (1.3mmol) at one time after the completion of dropwise addition, slowly adding pyridine (4mmol) by using the constant-pressure dropping funnel, adding 5ml acetonitrile, slowly adding methanesulfonyl chloride (2mmol) by using the constant-pressure dropping funnel after the completion of dropwise addition, removing the ice bath after the completion of the dropwise addition, extracting a reaction solution by using dichloromethane and water after the completion of the reaction, mixing an organic layer with a sample, and using V to mix the sample by using an organic layerPetroleum ether：VEthyl acetatePassing the obtained product through a column at a ratio of 10:1 to obtain trifluoromethyl pyridinoxazone;
the second step is that:
adding trifluoromethyl pyridinoxazone (1mmol) and 10ml acetonitrile, stirring, slowly adding a mixed solution of (R) -1- (methylthio) propan-2-amine (10mmol) and 9ml acetonitrile dropwise through a constant pressure dropping funnel, gradually separating out solids from a clear solution after the dropwise addition is finished, and carrying out suction filtration to obtain the target compound.
Physical and chemical properties of 1703R: white solid, 76.04%, 172-; 1H NMR(400MHz,CDCl3)δ10.26(s, 1H),8.84(d,J＝1.1Hz,1H),8.12(d,J＝1.3Hz,1H),7.13(ddd,J＝7.9,2.7,1.5Hz,1H),7.09–7.01 (m,1H),6.42(d,J＝7.9Hz,1H),4.29(tt,J＝12.8,6.4Hz,1H),2.67(d,J＝6.2Hz,2H),2.09(s,3H), 1.29(d,J＝6.7Hz,3H). 13C NMR(101MHz,CDCl3)δ165.32,161.73(d,J＝12.3Hz),160.84, 159.02(dd,J＝41.3,12.3Hz),158.88,158.76,156.34,156.21,147.96,143.15(d,J＝3.8Hz),137.90 (d,J＝3.6Hz),134.37(d,J＝7.9Hz),132.83,129.71(d,J＝34.1Hz),122.10(d,J＝273.6Hz), 119.30(dd,J＝14.2,4.2Hz),110.42(dd,J＝23.6,3.6Hz),107.15,106.77(d,J＝25.5Hz),45.01, 40.51,29.72,19.77,16.27. 19FNMR(376MHz,CDCl3)δ-62.57,-109.91,-109.94,-110.10, -110.12.HRMS(ESI):Calculated for C18H15O2N3ClF5S[M+H]+:468.05664,found:468.05563.
example 7: preparation of 1704S
The first step is as follows:
adding 3-chloro-5-trifluoromethylpyridine acid (1mmol), pyridine (4mmol) and 10ml acetonitrile into a 50ml three-necked bottle, stirring under an ice salt bath, slowly adding methanesulfonyl chloride (2mmol) by using a constant-pressure dropping funnel, adding 2-amino-3, 5-dichlorobenzoic acid (1.3mmol) at one time after the completion of dropwise addition, slowly adding pyridine (4mmol) by using the constant-pressure dropping funnel, adding 5ml acetonitrile, slowly adding methanesulfonyl chloride (2mmol) by using the constant-pressure dropping funnel after the completion of dropwise addition, removing the ice bath after the completion of reaction, extracting a reaction solution by using dichloromethane and water, mixing an organic layer with a sample, and using V to mix the sample with the organic layerPetroleum ether：VEthyl acetatePassing the obtained product through a column at a ratio of 10:1 to obtain trifluoromethyl pyridinoxazone;
the second step is that:
adding trifluoromethyl pyridinoxazone (1mmol) and 10ml acetonitrile, stirring, slowly adding a mixed solution of (S) -1- (methylthio) propan-2-amine (10mmol) and 9ml acetonitrile dropwise through a constant pressure dropping funnel, gradually separating out solids from a clear solution after the dropwise addition is finished, and carrying out suction filtration to obtain the target compound.
Physicochemical properties of 1704S: white solid, 75.71%, 219-220 ℃; 1H NMR(400MHz,CDCl3)δ10.07(s, 1H),8.84(d,J＝0.9Hz,1H),8.12(d,J＝1.2Hz,1H),7.55(d,J＝2.3Hz,1H),7.46(d,J＝2.3Hz, 1H),6.52(d,J＝8.1Hz,1H),4.26(dt,J＝14.4,6.4Hz,1H),2.65(tt,J＝13.5,6.7Hz,2H),2.09(s, 3H),1.28(d,J＝6.7Hz,3H). 13C NMR(101MHz,CDCl3)δ165.61,160.85,147.67,143.09(d,J＝3.8 Hz),138.02(d,J＝3.6Hz),136.18,132.96,132.92,132.41,131.14,129.86(d,J＝34.1Hz),126.88, 122.06(d,J＝273.5Hz).45.00,40.41,19.64,16.18. 19FNMR(376MHz,CDCl3)δ-62.57.HRMS(ESI):Calculated for C18H15O2N3Cl3F3S[M+H]+:499.99754,found:499.99658.
example 8: 1704R preparation
The first step is as follows:
adding 3-chloro-5-trifluoromethylpyridine acid (1mmol), pyridine (4mmol) and 10ml acetonitrile into a 50ml three-necked bottle, stirring under an ice salt bath, slowly adding methanesulfonyl chloride (2mmol) by using a constant-pressure dropping funnel, adding 2-amino-3, 5-dichlorobenzoic acid (1.3mmol) at one time after the completion of dropwise addition, slowly adding pyridine (4mmol) by using the constant-pressure dropping funnel, adding 5ml acetonitrile, slowly adding methanesulfonyl chloride (2mmol) by using the constant-pressure dropping funnel after the completion of dropwise addition, removing the ice bath after the completion of reaction, extracting a reaction solution by using dichloromethane and water, mixing an organic layer with a sample, and using V to mix the sample with the organic layerPetroleum ether：VEthyl acetatePassing the obtained product through a column at a ratio of 10:1 to obtain trifluoromethyl pyridinoxazone;
the second step is that:
adding trifluoromethyl pyridinoxazone (1mmol) and 10ml acetonitrile, stirring, slowly adding a mixed solution of (R) -1- (methylthio) propan-2-amine (10mmol) and 9ml acetonitrile dropwise through a constant pressure dropping funnel, gradually separating out solids from a clear solution after the dropwise addition is finished, and carrying out suction filtration to obtain the target compound.
Physicochemical properties of 1704R: white solid, 42.34%, 210-; 1H NMR(400MHz,CDCl3)δ10.26(s, 1H),8.84(d,J＝1.1Hz,1H),8.12(d,J＝1.3Hz,1H),7.13(ddd,J＝7.9,2.7,1.5Hz,1H),7.09–7.01 (m,1H),6.42(d,J＝7.9Hz,1H),4.29(tt,J＝12.8,6.4Hz,1H),2.67(d,J＝6.2Hz,2H),2.09(s,3H), 1.29(d,J＝6.7Hz,3H). 13C NMR(101MHz,CDCl3)δ165.58,160.82,147.61,143.07(d,J＝3.8Hz), 138.02(d,J＝3.6Hz),136.17,132.97,132.92,132.41,131.15,129.86(d,J＝34.1Hz),126.87,122.05 (d,J＝273.6Hz).44.99,40.41,29.71,19.64,18.61,16.18,12.10. 19F NMR(376MHz,CDCl3)δ -62.56.HRMS(ESI):Calculated for C18H15O2N3Cl3F3S[M+H]+:499.99754,found:499.99658.
example 9: 1705S preparation
The first step is as follows:
adding 3-chloro-5-trifluoromethylpyridine acid (1mmol), pyridine (4mmol) and 10ml acetonitrile into a 50ml three-necked bottle, stirring under an ice salt bath, slowly adding methanesulfonyl chloride (2mmol) by using a constant-pressure dropping funnel, adding 2-amino-5-chlorobenzoic acid (1.3mmol) at one time after the dropwise addition is finished, slowly adding pyridine (4mmol) by using the constant-pressure dropping funnel, adding 5ml acetonitrile, slowly adding methanesulfonyl chloride (2mmol) by using the constant-pressure dropping funnel after the dropwise addition is finished, removing the ice bath after the dropwise addition is finished, extracting a reaction solution by using dichloromethane and water after the reaction is finished, mixing an organic layer with a sample, and stirring the sample by using VPetroleum ether：VEthyl acetatePassing the obtained product through a column at a ratio of 10:1 to obtain trifluoromethyl pyridinoxazone;
the second step is that:
adding trifluoromethyl pyridinoxazone (1mmol) and 10ml acetonitrile, stirring, slowly adding a mixed solution of (S) -1- (methylthio) propan-2-amine (10mmol) and 9ml acetonitrile dropwise through a constant pressure dropping funnel, gradually separating out solids from a clear solution after the dropwise addition is finished, and carrying out suction filtration to obtain the target compound.
Physicochemical properties of 1705S: pale yellow solid, 19.21%, 197-; 1H NMR(400MHz,CDCl3)δ12.52 (s,1H),8.90(d,J＝1.1Hz,1H),8.79(d,J＝8.8Hz,1H),8.11(d,J＝1.3Hz,1H),7.51(t,J＝3.1Hz, 1H),7.49–7.46(m,1H),6.40(d,J＝7.5Hz,1H),4.49–4.23(m,1H),2.76(dd,J＝5.8,3.0Hz,2H), 2.17(s,3H),1.37(d,J＝6.7Hz,3H). 13CNMR(101MHz,CDCl3)δ166.86,161.03,149.67,143.40(d, J＝3.9Hz),137.68(d,J＝3.6Hz),137.13,132.38,132.31,129.28(d,J＝33.9Hz),128.76,126.74, 122.18(d,J＝273.5Hz).45.03,40.62,29.72,19.93,16.49. 19F NMR(376MHz,CDCl3)δ-62.55. HRMS(ESI):Calculated for C18H16O2N3Cl2F3S[M+H]+:466.03651,found:466.03647.
example 10: 1705R preparation
The first step is as follows:
adding 3-chloro-5-trifluoromethylpyridine acid (1mmol), pyridine (4mmol) and 10ml acetonitrile into a 50ml three-necked bottle, stirring under an ice salt bath, slowly adding methanesulfonyl chloride (2mmol) by using a constant-pressure dropping funnel, adding 2-amino-5-chlorobenzoic acid (1.3mmol) at one time after the dropwise addition is finished, slowly adding pyridine (4mmol) by using the constant-pressure dropping funnel, adding 5ml acetonitrile, slowly adding methanesulfonyl chloride (2mmol) by using the constant-pressure dropping funnel after the dropwise addition is finished, removing the ice bath after the dropwise addition is finished, extracting a reaction solution by using dichloromethane and water after the reaction is finished, mixing an organic layer with a sample, and stirring the sample by using VPetroleum ether：VEthyl acetatePassing the obtained product through a column at a ratio of 10:1 to obtain trifluoromethyl pyridinoxazone;
the second step is that:
adding trifluoromethyl pyridinoxazone (1mmol) and 10ml acetonitrile, stirring, slowly adding a mixed solution of (R) -1- (methylthio) propan-2-amine (10mmol) and 9ml acetonitrile dropwise through a constant pressure dropping funnel, gradually separating out solids from a clear solution after the dropwise addition is finished, and carrying out suction filtration to obtain the target compound.
Physical and chemical properties of 1705R: pale yellow solid, 72.02%, 190-; 1H NMR(400MHz,CDCl3)δ12.52 (s,1H),8.90(d,J＝1.1Hz,1H),8.78(d,J＝8.9Hz,1H),8.11(d,J＝1.3Hz,1H),7.51(d,J＝2.4Hz, 1H),7.48(dd,J＝8.9,2.4Hz,1H),6.41(d,J＝7.7Hz,1H),4.49–4.34(m,1H),2.76(dd,J＝5.8,2.8 Hz,2H),2.17(s,3H),1.37(d,J＝6.7Hz,3H). 13C NMR(101MHz,CDCl3)δ166.86,161.03,149.65, 143.40(d,J＝3.9Hz),137.68(d,J＝3.6Hz),137.12,132.38,132.31,129.28(d,J＝34.0Hz),128.75, 126.76,122.18(d,J＝273.4Hz).45.03,40.61,19.93,16.49. 19FNMR(376MHz,CDCl3)δ-62.55. HRMS(ESI):Calculated for C18H16O2N3Cl2F3S[M+H]+:466.03651,found:466.03653.
example 11: preparation of 1706S
The first step is as follows:
adding 3-chloro-5-trifluoromethylpyridine acid (2mmol) and sodium ethanethiol (2mmol) into 5mL DMF, heating to 50 deg.C, stirring for 5 hr, after the reaction is finished, pouring the reaction solution into 20mL water, adjusting pH to 5, and filtering to obtain 3-ethylthio-5-trifluoromethylpyridine acid.
The second step is that:
adding 3-ethylthio-5-trifluoromethylpyridine acid (1mmol), pyridine (4mmol) and 10ml acetonitrile into a 50ml three-necked bottle, stirring under an ice salt bath, slowly adding methanesulfonyl chloride (2mmol) by using a constant-pressure dropping funnel, adding 2-amino-3-methyl-5-chlorobenzoic acid (1.3mmol) at one time after the dropwise addition is finished, slowly adding pyridine (4mmol) by using the constant-pressure dropping funnel, adding 5ml acetonitrile, slowly adding methanesulfonyl chloride (2mmol) by using the constant-pressure dropping funnel after the dropwise addition is finished, removing the ice bath after the dropwise addition is finished, extracting a reaction solution by using dichloromethane and water after the reaction is finished, mixing an organic layer with a sample, and using V to mix the samplePetroleum ether：VEthyl acetatePassing the obtained product through a column at a ratio of 10:1 to obtain trifluoromethyl pyridinoxazone;
the third step:
adding trifluoromethyl pyridinoxazone (1mmol) and 10ml acetonitrile, stirring, slowly adding a mixed solution of (S) -1- (methylthio) propan-2-amine (10mmol) and 9ml acetonitrile dropwise through a constant pressure dropping funnel, gradually separating out solids from a clear solution after the dropwise addition is finished, and carrying out suction filtration to obtain the target compound.
Physicochemical properties of 1706S: 1H NMR(400MHz,CDCl3)δ10.07(s,1H),8.84(d,J＝0.9Hz,1H),8.12 (d,J＝1.2Hz,1H),7.55(d,J＝2.3Hz,1H),7.46(d,J＝2.3Hz,1H),6.52(d,J＝8.1Hz,1H),4.26(dt, J＝14.4,6.4Hz,1H),3.00((tt,J＝13.5,6.7Hz,2H)2.65(tt,J＝13.5,6.7Hz,2H),2.09(s,3H),1.31(d, J＝6.7Hz,3H)1.28(d,J＝6.7Hz,3H).
example 12: preparation of 1706R
The first step reaction operates ketone example 11.
The second step is that:
adding 3-ethylthio-5-trifluoromethylpyridine acid (1mmol), pyridine (4mmol) and 10ml acetonitrile into a 50ml three-necked bottle, stirring under an ice salt bath, slowly adding methanesulfonyl chloride (2mmol) by using a constant-pressure dropping funnel, adding 2-amino-3-methyl-5-chlorobenzoic acid (1.3mmol) at one time after the dropwise addition is finished, slowly adding pyridine (4mmol) by using the constant-pressure dropping funnel, adding 5ml acetonitrile, slowly adding methanesulfonyl chloride (2mmol) by using the constant-pressure dropping funnel after the dropwise addition is finished, removing the ice bath after the dropwise addition is finished, extracting a reaction solution by using dichloromethane and water after the reaction is finished, mixing an organic layer with a sample, and using V to mix the samplePetroleum ether：VEthyl acetatePassing the obtained product through a column at a ratio of 10:1 to obtain trifluoromethyl pyridinoxazone;
the third step:
adding trifluoromethyl pyridinoxazone (1mmol) and 10ml acetonitrile, stirring, slowly adding a mixed solution of (R) -1- (methylthio) propan-2-amine (10mmol) and 9ml acetonitrile dropwise through a constant pressure dropping funnel, gradually separating out solids from a clear solution after the dropwise addition is finished, and carrying out suction filtration to obtain the target compound.
Physicochemical properties of 1706R: 1H NMR(400MHz,CDCl3)δ10.07(s,1H),8.86(d,J＝0.9Hz,1H),8.17 (d,J＝1.2Hz,1H),7.54(d,J＝2.3Hz,1H),7.49(d,J＝2.3Hz,1H),6.59(d,J＝8.1Hz,1H),4.24(dt, J＝14.4,6.4Hz,1H),3.06((tt,J＝13.5,6.7Hz,2H)2.68(tt,J＝13.5,6.7Hz,2H),2.17(s,3H),1.34(d, J＝6.7Hz,3H)1.29(d,J＝6.7Hz,3H).
example 13: 1707S preparation
The reaction procedure in the first step was the same as in example 11.
The second step is that:
3-ethylsulfanyl-5-trifluoromethylpyridine acid (1.5mmol) was dissolved in 20mL of absolute ethanol, ammonium molybdate (2mmol) was added as a catalyst, and 15mmol of H was added2O2(30％) Heating to 50 ℃ for reaction, removing ethanol in the reaction solution under reduced pressure after the reaction is finished, pouring the residual solution into 20mL of water, adjusting the pH value to 5, and filtering to obtain the 3-ethylsulfonyl-5-trifluoromethyl pyridine acid.
The third step:
adding 3-ethylsulfonyl-5-trifluoromethylpyridine acid (1mmol), pyridine (4mmol) and 10ml acetonitrile into a 50ml three-necked flask, stirring in an ice salt bath, slowly adding methanesulfonyl chloride (2mmol) by using a constant-pressure dropping funnel, adding 2-amino-3-methyl-5-chlorobenzoic acid (1.3mmol) at one time after the dropwise addition is finished, slowly adding pyridine (4mmol) by using the constant-pressure dropping funnel, adding 5ml acetonitrile, slowly adding methanesulfonyl chloride (2mmol) by using the constant-pressure dropping funnel after the dropwise addition is finished, removing the ice bath after the dropwise addition is finished, extracting a reaction solution by using dichloromethane and water after the reaction is finished, mixing an organic layer with a sample, and using V to mix the samplePetroleum ether：VEthyl acetatePassing the obtained product through a column at a ratio of 10:1 to obtain trifluoromethyl pyridinoxazone;
the fourth step:
adding ethylsulfonyl trifluoromethyl pyridinoxazone (1mmol) and 10ml acetonitrile, stirring, slowly adding a mixed solution of (S) -1- (methylthio) propan-2-amine (10mmol) and 9ml acetonitrile dropwise through a constant pressure dropping funnel, gradually separating out solids from the clear solution after the dropwise addition is finished, and filtering to obtain the target compound.
Physicochemical properties of 1707S: off-white solid, 46% yield, 1H NMR(400MHz,CDCl3)δ10.07(s,1H),8.84 (d,J＝0.9Hz,1H),8.12(d,J＝1.2Hz,1H),7.55(d,J＝2.3Hz,1H),7.46(d,J＝2.3Hz,1H),6.52(d, J＝8.1Hz,1H),4.26(dt,J＝14.4,6.4Hz,1H),3.51((tt,J＝13.5,6.7Hz,2H)2.65(tt,J＝13.5,6.7Hz, 2H),2.09(s,3H),1.28(d,J＝6.7Hz,3H).1.19(d,J＝6.7Hz,3H).
example 14: 1707R preparation
The reaction operations in the first to third steps were the same as in example 13.
The fourth step:
adding ethylsulfonyl-trifluoromethyl pyridinoxazone ketone (1mmol) and 10ml acetonitrile, stirring, slowly dropwise adding a mixed solution of (R) -1- (methylthio) propan-2-amine (10mmol) and 9ml acetonitrile by using a constant-pressure dropping funnel, completing dropwise adding, gradually separating out solids from a clear solution, and performing suction filtration to obtain the target compound.
1707S，(C21H23ClF3N3O4S2) 1H NMR(400MHz,CDCl3)δ10.06(s,1H),8.894(d,J＝0.9Hz, 1H),8.17(d,J＝1.2Hz,1H),7.57(d,J＝2.3Hz,1H),7.46(d,J＝2.3Hz,1H),6.54(d,J＝8.1Hz, 1H),4.28(dt,J＝14.4,6.4Hz,1H),3.54((tt,J＝13.5,6.7Hz,2H)2.66(tt,J＝13.5,6.7Hz,2H),2.08(s, 3H),1.32(d,J＝6.7Hz,3H).1.16(d,J＝6.7Hz,3H).
Example 15: test for antiviral Activity of target Compound (anti-tobacco mosaic Virus)
The anti-plant virus activity of the compound is determined by a half-leaf withered spot method. 2mg of the target compound was weighed into a 14mL centrifuge tube, 40. mu.L DMSO was added to dissolve the target compound sufficiently, and 4mL of secondary water containing 1% Tween20 was added to prepare a 500. mu.g/mL compound solution. Another 25. mu.L of 80% ningnanmycin preparation was added with 4mL of secondary water containing 1% Tween20 to prepare 500. mu.g/mL ningnanmycin solution.
Therapeutic activity of an agent against TMV virus. Selecting heart leaf tobacco with consistent growth vigor, dipping virus liquid by using a row pen, and performing friction inoculation on leaf surfaces (whole leaves) along the branch vein direction of the leaf surfaces on the leaf blades scattered with carborundum, wherein the inoculation dynamics of the left and right leaf blades are kept consistent as much as possible, and the lower parts of the leaf blades are supported by a culture dish. And (3) after the virus is on the leaves for about half an hour, washing carborundum on the leaves with running water, after the leaves are dried, coating a medicament on the left half leaves, then putting the left half leaves into a greenhouse for culturing, and observing and recording the number of the generated withered spots after 2-3 days. The inhibition rate was calculated in triplicate per dose according to the above method.
Protective activity of an agent against TMV virus. Selecting the heart-leaf tobacco with consistent growth vigor, applying the medicament on the left half leaf by using a writing brush, and inoculating the virus after 24 hours. Dipping the virus liquid with a row of pens, and frictionally inoculating the leaf surfaces (whole leaves) on the leaves scattered with carborundum along the branch vein direction, wherein the inoculating force of the left and right leaves is kept consistent as much as possible, and the lower parts of the leaves are supported by a culture dish. After the virus acts on the leaf for half an hour, the carborundum on the leaf is washed by running water, then the leaf is placed in a greenhouse for culturing, and the number of the generated withered spots is observed and recorded after 2-3 days. The inhibition rate was calculated in triplicate per dose according to the above method.
Inactivating activity of the agent against TMV virus. Selecting heart leaf tobacco with consistent growth vigor, scattering carborundum on the whole leaf, supporting a culture dish below the leaf, inoculating virus on the right leaf, inoculating a medicament which acts with the virus for half an hour on the left leaf, flushing the carborundum on the leaf with running water after half an hour of inoculation, placing the leaf in a greenhouse for culture, and observing and recording the number of dead spots after 2-3 days. The inhibition rate was calculated as three replicates per dose according to the above method
Wherein: y represents the inhibition rate of the compound on tobacco mosaic virus, CK represents the number of dead spots of a control group (right hemiphyllae virus), and A represents the number of dead spots of an applied medicament (left hemiphyllae). The embodiment of the present invention is provided to illustrate the technical solution of the present invention, but the implementation content is not limited thereto, and the experimental results are shown in table 1.
TABLE 1 inhibitory Activity of chiral thioether trifluoromethylpyridine amide derivatives on plant Virus TMV
TABLE 2 EC of part of the target Compounds against plant Virus TMV50Value of
The experimental result shows that the compound 1701R and 1703S have better therapeutic activity on TMV than ningnanmycin and higher anti-tobacco mosaic virus activity at 500 mu g/mL.
Example 16 insecticidal Activity test of the object Compound (Plutella xylostella)
By adopting a leaf soaking method, 4mg of medicine is accurately weighed, 80 mu LDMSO is added to fully dissolve the medicine, 8mL and 4mL of secondary water containing 1% Tween20 are added to respectively prepare compound solutions of 500 mu g/mL and 250 mu g/mL. The cabbage with uniform size is placed in the prepared medicament to be soaked for 15S, the cabbage is taken out to be placed in culture dishes with moist filter paper, after the medicament is dried, 10 diamondback moths with second age are captured in each culture dish, the culture dishes are covered and placed in an incubator to be cultured, three parallel tests are carried out on each medicament, Tween water without the medicament is used as a blank control group, and survival data of the diamondback moths are observed and recorded after 72 h.
Calculating mortality
In the formula: p1-mortality; k-number of dead insects; N-Total number of insects treated
In the formula: p2-correcting mortality; pt-treatment mortality; p0Blank control mortality. Mortality rate if control<5%, no correction is needed; control mortality was between 5% and 20% and should be corrected for according to equation (2); control mortality>20%, the experiment needs to be redone.
TABLE 3 insecticidal Activity of target Compounds against Plutella xylostella
The experimental results in table 3 show that the compounds have good insecticidal activity against plutella xylostella.
Pharmacological example 17: insecticidal activity against armyworm
3mL of the solution is transferred and added into 27g of the feed which is just prepared by adopting a feed mixing method to obtain the required concentration which is ten times diluted. Uniformly mixing the medicines, uniformly pouring the medicines into a clean 24-hole plate, cooling, inoculating 24 armyworms, observing for 3-4 days, and checking the result.
The activity results of some compounds are shown in Table 4
Calculated mortality and corrected mortality:
in the formula: p1-mortality; k-number of dead insects; n-total number of insects treated.
In the formula: p2-corrected mortality; pt-treatment mortality; p0-blank control mortality. If the control mortality rate is less than 5%, no correction is needed; the control mortality rate is between 5 and 20%, and should be corrected according to formula (2); control mortality was > 20%, and the test was redone.
TABLE 4 insecticidal Activity of the target Compounds against armyworms
The experimental results in table 4 show that the compounds have good insecticidal activity against armyworm.
Pharmacological example 18: insecticidal activity against corn borer
3mL of the solution is transferred and added into 27g of the feed which is just prepared by adopting a feed mixing method to obtain the required concentration which is ten times diluted. Uniformly mixing the medicaments, uniformly pouring the mixture into a clean 24-hole plate, cooling the mixture, inoculating the cooled mixture into 24-head corn borers, and observing the observation result after 3 to 4 days.
The activity results of some compounds are shown in Table 5
Calculated mortality and corrected mortality:
in the formula: p1-mortality; k-number of dead insects; n-total number of insects treated.
In the formula: p2-corrected mortality; pt-treatment mortality; p0-blank control mortality. If the control mortality rate is less than 5%, no correction is needed; the control mortality rate is between 5 and 20%, and should be corrected according to formula (2); control mortality was > 20%, and the test was redone.
TABLE 5 insecticidal Activity of target Compounds against corn borer
The experimental results of table 5 show that the compounds have good insecticidal activity against corn borer.
Claims (5)
1. A trifluoromethyl pyridine amide compound containing chiral thioether is characterized in that: the general structural formula is shown as I:
the general formula is shown as I: c marked represents a chiral carbon atom; r represents C1-C3 alkyl, halogen, haloalkyl, cyano, nitro, alkoxy or alkylthio, or is substituted by more than one; r1Is hydrogen atom, halogen atom, alkyl, C1-C4 alkoxy, C1-C4 alkylthio or C1-C4 sulfonyl; r2Is C1-C5 alkyl.
2. The compound of claim 1, wherein C is a chiral carbon atom; r represents methyl, halogen, cyano or nitro, or more than one substituent; r1Hydrogen atom, Cl, Br, F, methyl, C1-C2 alkoxy, C1-C2 alkylthio or C1-C2 sulfonyl; r2Is C1-C3 alkyl.
3. The compound of claim 2, wherein C is a chiral carbon atom; r is methyl orHalogen, or one or more substitutions; r1Is Cl, ethylthio or ethylsulfonyl; r2Is C1-C2 alkyl.
4. Use of a compound according to any one of claims 1 to 3 for the preparation of a pesticide or pesticide additive for controlling diamondback moth, armyworm, corn borer or TMV.
5. Use of a compound according to any one of claims 1 to 3 for the preparation of a pesticide or pesticide additive for controlling crop pests or viral diseases.
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| WO2022013417A1 (en) | 2020-07-17 | 2022-01-20 | Syngenta Crop Protection Ag | Pesticidally active heterocyclic derivatives with sulfur containing substituents |
| WO2022017975A1 (en) | 2020-07-18 | 2022-01-27 | Syngenta Crop Protection Ag | Pesticidally active heterocyclic derivatives with sulfur containing substituents |
| WO2022049146A1 (en) | 2020-09-02 | 2022-03-10 | Syngenta Crop Protection Ag | Pesticidally active heterocyclic derivatives with sulfur containing substituents |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001070671A2 (en) * | 2000-03-22 | 2001-09-27 | E.I. Du Pont De Nemours And Company | Insecticidal anthranilamides |
| CN101006049A (en) * | 2004-08-23 | 2007-07-25 | 日本农药株式会社 | Optically active phthalamide derivative, insecticide for agriculture and horticulture and use thereof |
| CN103172613A (en) * | 2013-01-05 | 2013-06-26 | 南开大学 | O-formylamino benzamide derivative containing N-cyano sulfone(sulfur) imine and preparation method and use thereof |
| JPWO2014021468A1 (en) * | 2012-07-31 | 2016-07-21 | 住友化学株式会社 | Amide compounds |
| CN106458909A (en) * | 2014-05-19 | 2017-02-22 | 先正达参股股份有限公司 | Insecticidally active amide derivatives with sulfur-substituted phenyl or pyridine groups |
| CN107098869A (en) * | 2017-05-03 | 2017-08-29 | 贵州大学 | Bisamide class compound containing 1,3,4 oxadiazolyls and preparation method and application |
| CN107759518A (en) * | 2017-07-27 | 2018-03-06 | 贵州大学 | A kind of phthaloyl amide derivatives and its application containing trifluoromethyl pyridine |
| CN109265381A (en) * | 2018-08-28 | 2019-01-25 | 中国农业大学 | A kind of phthaloyl amide derivatives of cyano-containing and its preparation and application |
-
2019
- 2019-07-23 CN CN201910667448.1A patent/CN110606828A/en active Pending
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001070671A2 (en) * | 2000-03-22 | 2001-09-27 | E.I. Du Pont De Nemours And Company | Insecticidal anthranilamides |
| CN101006049A (en) * | 2004-08-23 | 2007-07-25 | 日本农药株式会社 | Optically active phthalamide derivative, insecticide for agriculture and horticulture and use thereof |
| JPWO2014021468A1 (en) * | 2012-07-31 | 2016-07-21 | 住友化学株式会社 | Amide compounds |
| CN103172613A (en) * | 2013-01-05 | 2013-06-26 | 南开大学 | O-formylamino benzamide derivative containing N-cyano sulfone(sulfur) imine and preparation method and use thereof |
| CN106458909A (en) * | 2014-05-19 | 2017-02-22 | 先正达参股股份有限公司 | Insecticidally active amide derivatives with sulfur-substituted phenyl or pyridine groups |
| CN107098869A (en) * | 2017-05-03 | 2017-08-29 | 贵州大学 | Bisamide class compound containing 1,3,4 oxadiazolyls and preparation method and application |
| CN107759518A (en) * | 2017-07-27 | 2018-03-06 | 贵州大学 | A kind of phthaloyl amide derivatives and its application containing trifluoromethyl pyridine |
| CN109265381A (en) * | 2018-08-28 | 2019-01-25 | 中国农业大学 | A kind of phthaloyl amide derivatives of cyano-containing and its preparation and application |
Non-Patent Citations (4)
| Title |
|---|
| HUA, XUEWEN，等: "Novel Anthranilic Diamide Insecticides: Design, Synthesis, and Insecticidal Evaluation", 《AUSTRALIAN JOURNAL OF CHEMISTRY》 * |
| ZHOU, SHA，等: "The exploration of chiral N-cyano sulfiliminyl dicarboxamides on insecticidal activities", 《CHINESE CHEMICAL LETTERS》 * |
| 王翔，等: "酰胺类化合物的合成及农药生物活性研究进展", 《精细化工中间体》 * |
| 邹骆波，等: "邻苯双酰胺类杀虫活性化合物的研究进展", 《现代农药》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2022013417A1 (en) | 2020-07-17 | 2022-01-20 | Syngenta Crop Protection Ag | Pesticidally active heterocyclic derivatives with sulfur containing substituents |
| WO2022017975A1 (en) | 2020-07-18 | 2022-01-27 | Syngenta Crop Protection Ag | Pesticidally active heterocyclic derivatives with sulfur containing substituents |
| WO2022049146A1 (en) | 2020-09-02 | 2022-03-10 | Syngenta Crop Protection Ag | Pesticidally active heterocyclic derivatives with sulfur containing substituents |
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