Preparation method of meta-phosphorylated polysubstituted pyridine compound

Abstract

The invention discloses a preparation method of meta-phosphorylated polysubstituted pyridine compounds, and belongs to the technical field of organic synthesis. The synthesis process is simple, highly toxic reagents, various catalysts and expensive noble metal catalysts do not need to be used, tert-olefin amide and an organophosphorus reagent are used as basic raw materials, manganese acetate is used as an accelerant (conventional reaction reagents, solvents and accelerants are utilized), and the tert-olefin amide is synthesized through an intramolecular free radical cascade reaction. The meta-phosphorylated polysubstituted pyridine compound can be efficiently obtained in one step, and the yield is as high as 95%; in addition, the reaction raw materials are cheap and easy to obtain, the atom economy is high, the substrate universality is wide, and the operability is high. The meta-phosphorylated polysubstituted pyridine compound disclosed by the invention has relatively good insecticidal activity on beet armyworm larvae, and can be applied to agricultural pest control as an insecticide.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, and in particular to a method for preparing meta-phosphonylated multi-substituted pyridine compounds. Background Art

[0002] Pyridine compounds are a very important class of organic compounds, widely present in natural products, drug molecules and functional materials, among which phosphonylated pyridine is a subclass with unique structure and properties. The introduction of phosphorus atoms makes this class of compounds have a wide range of physiological activities and has important applications in the fields of medicine and pesticides; after reduction, the phosphorus-oxygen double bond is a common nitrogen-phosphorus ligand, which has a wide range of applications in transition metal-catalyzed organic synthesis; in addition, the phosphonyl group can also be used as a directing group or activating functional group to further derivatize and produce more nitrogen heterocyclic compounds.

[0003] People have been seeking simple and efficient methods for preparing phosphonylated pyridine compounds. However, due to the inherent electronic properties of the pyridine ring, most of the existing synthetic methods can only prepare ortho- or para-phosphonylated pyridine compounds, and there is limited research on the synthesis of meta-phosphonylated pyridine compounds. There are also some methods in the prior art that can synthesize meta-phosphonylated pyridine compounds, but there are problems such as the need to use expensive transition metal catalysts and ligands, poor functional group compatibility, poor substrate universality, and unsuitability for the preparation of polysubstituted pyridines. Therefore, the development of simple and efficient synthetic strategies and the use of cheap and readily available chemical reagents to prepare meta-phosphonylated pyridine compounds under mild reaction conditions have good application prospects. Summary of the invention

[0004] The purpose of the present invention is to provide a method for preparing meta-phosphonylated polysubstituted pyridine compounds to solve the problems existing in the above-mentioned prior art.

[0005] To achieve the above object, the present invention provides the following solutions:

[0006] One of the technical solutions of the present invention is: a meta-phosphonylated multi-substituted pyridine compound, the structural formula of which is shown in formula (1):

[0007]

[0008] Among them, R 2 is an aryl group; R 3 is a hydrogen atom, an alkyl group or an aryl group; R 4 is an alkyl group or an aryl group; R 5 is an alkoxy group or an aryl group; R 6 is an alkoxy group or an aryl group.

[0009] Preferably, the R 2When it is aryl, specifically phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 3-bromophenyl, 2-bromophenyl, 4-methylphenyl, 3-methylphenyl, 2-methylphenyl, 4-methoxyphenyl, 2-naphthyl or 1-naphthyl;

[0010] The R 3 When it is an alkyl group, it is specifically a methyl group or an ethyl group; 3 When it is an aryl group, specifically phenyl, 4-chlorophenyl, 4-bromophenyl, 3-bromophenyl, 2-bromophenyl, 4-methylphenyl or 4-methoxyphenyl;

[0011] The R 4 When it is an alkyl group, it is specifically a methyl group or an ethyl group; 4 When it is an aryl group, specifically phenyl, 4-methoxyphenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 4-chlorophenyl, 4-cyanophenyl, 4-trifluoromethylphenyl, 4-phenylphenyl, 2-naphthyl, 1-naphthyl, pyridyl or thienyl;

[0012] The R 5 When it is an alkoxy group, it is specifically methoxy, ethoxy or isopropoxy; the R 5 When it is an aryl group, specifically phenyl, 4-methoxyphenyl, 4-methylphenyl, 4-chlorophenyl, 4-bromophenyl, 2-methylphenyl or 3,5-dimethylphenyl;

[0013] The R 6 When it is an alkoxy group, it is specifically methoxy, ethoxy or isopropoxy; the R 6 When it is an aryl group, specifically, it is phenyl, 4-methoxyphenyl, 4-methylphenyl, 4-chlorophenyl, 4-bromophenyl, 2-methylphenyl or 3,5-dimethylphenyl.

[0014] The second technical solution of the present invention is a method for preparing the above-mentioned meta-phosphonylated multi-substituted pyridine compound, comprising the following steps:

[0015] Adding compound 1 (tertiary olefin amide) and compound 2 (organophosphorus reagent) into an organic solvent, then adding a promoter, and heating for reaction to obtain the meta-phosphonylated multi-substituted pyridine compound;

[0016] The structural formula of the compound 1 is as follows:

[0017]

[0018] The structural formula of the compound 2 is as follows:

[0019]

[0020] Among them, R 1 is alkyl, alkoxy or aryl; R2 is an aryl group; R 3 is a hydrogen atom, an alkyl group or an aryl group; R 4 is an alkyl group or an aryl group; R 5 is an alkoxy group or an aryl group; R 6 is an alkoxy group or an aryl group.

[0021] Preferably, the R 1 When it is an alkyl group, it is specifically methyl, ethyl or isopropyl;

[0022] The R 1 When it is an alkoxy group, it is specifically tert-butoxy or benzyloxy;

[0023] The R 1 When it is an aryl group, specifically, it is phenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 4-methylphenyl, 4-methoxyphenyl, 4-chlorophenyl, 4-fluorophenyl or 4-nitrophenyl.

[0024] The R 2 When it is aryl, specifically phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 3-bromophenyl, 2-bromophenyl, 4-methylphenyl, 3-methylphenyl, 2-methylphenyl, 4-methoxyphenyl, 2-naphthyl or 1-naphthyl;

[0025] The R 3 When it is an alkyl group, it is specifically a methyl group or an ethyl group; 3 When it is an aryl group, specifically phenyl, 4-chlorophenyl, 4-bromophenyl, 3-bromophenyl, 2-bromophenyl, 4-methylphenyl or 4-methoxyphenyl;

[0026] The R 4 When it is an alkyl group, it is specifically a methyl group or an ethyl group; 4 When it is an aryl group, specifically phenyl, 4-methoxyphenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 4-chlorophenyl, 4-cyanophenyl, 4-trifluoromethylphenyl, 4-phenylphenyl, 2-naphthyl, 1-naphthyl, pyridyl or thienyl;

[0027] The R 5 When it is an alkoxy group, it is specifically methoxy, ethoxy or isopropoxy; the R 5 When it is an aryl group, specifically phenyl, 4-methoxyphenyl, 4-methylphenyl, 4-chlorophenyl, 4-bromophenyl, 2-methylphenyl or 3,5-dimethylphenyl;

[0028] The R 6 When it is an alkoxy group, it is specifically methoxy, ethoxy or isopropoxy; the R 6When it is an aryl group, specifically, it is phenyl, 4-methoxyphenyl, 4-methylphenyl, 4-chlorophenyl, 4-bromophenyl, 2-methylphenyl or 3,5-dimethylphenyl.

[0029] Preferably, the molar ratio of compound 1, compound 2 and accelerator is 1:(1-2):(2-4), more preferably 1:2:3.

[0030] The organic solvent includes any one of toluene, dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF) and acetic acid (AcOH), more preferably acetic acid (AcOH).

[0031] The accelerator includes manganese acetate.

[0032] Preferably, the usage ratio of the compound 1 and the organic solvent is 0.2 mmol:2.0 mL; preferably, the heating reaction temperature is 40-140° C., and the time is 5-20 h, more preferably 100-120° C., and the time is 5-6 h.

[0033] The third technical solution of the present invention: an application of the above-mentioned meta-phosphonylated multi-substituted pyridine compound as an agent for preventing agricultural pests.

[0034] Preferably, the agricultural pests include Spodoptera exigua.

[0035] The present invention discloses the following technical effects:

[0036] (1) The meta-phosphonylated polysubstituted pyridine compounds of the present invention have good insecticidal activity against beet armyworm larvae and can be used as insecticides in agricultural pest control.

[0037] (2) The synthesis process of the present invention is simple and does not require the use of highly toxic reagents, multiple catalysts, and expensive precious metal catalysts. It uses tertiary olefin amide and organic phosphorus reagent as basic raw materials and manganese acetate as a promoter (using conventional reaction reagents, solvents, and promoters). Through the intramolecular free radical cascade reaction, meta-phosphonylated polysubstituted pyridine compounds can be obtained in one step with high efficiency, and the yield is as high as 95%. In addition, the reaction raw materials of the present invention are cheap and easy to obtain, the atom economy is high, the substrate is widely universal, and the operability is strong.

[0038] (3) The reaction substrate organophosphorus reagent compound used in the present invention does not need to be prepared and is directly commercially available, thereby avoiding cumbersome reaction steps and improving the atom economy of the reaction.

[0039] (4) The reaction conditions involved in the present invention are relatively suitable, do not require high-pressure reaction, do not require a strict anhydrous and oxygen-free environment, are very simple to operate, have a high product yield, and the active groups can be further derivatized. DETAILED DESCRIPTION

[0040] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as limiting the present invention, but should be understood as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0041] It should be understood that the terms described in the present invention are only for describing special embodiments and are not intended to limit the present invention. In addition, for the numerical range in the present invention, it should be understood that each intermediate value between the upper and lower limits of the scope is also specifically disclosed. Each smaller range between the intermediate value in any stated value or stated range and any other stated value or intermediate value in the described range is also included in the present invention. The upper and lower limits of these smaller ranges can be independently included or excluded in the scope.

[0042] Unless otherwise indicated, all technical and scientific terms used herein have the same meanings as those generally understood by those skilled in the art. Although the present invention describes only preferred methods and materials, any methods and materials similar or equivalent to those described herein may also be used in the implementation or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials associated with the documents. In the event of a conflict with any incorporated document, the content of this specification shall prevail.

[0043] It will be apparent to those skilled in the art that various modifications and variations may be made to the specific embodiments of the present invention description without departing from the scope or spirit of the present invention. Other embodiments derived from the present invention description will be apparent to those skilled in the art. The present invention description and examples are exemplary only.

[0044] The words “include,” “including,” “have,” “contain,” etc. used in this document are open-ended terms, meaning including but not limited to.

[0045] To achieve the above object, the present invention provides the following solutions:

[0046] In a first aspect, the present invention provides a meta-phosphonylated multi-substituted pyridine compound, the structural formula of which is shown in formula (1):

[0047]

[0048] Among them, R 2 is an aryl group; R 3 is a hydrogen atom, an alkyl group or an aryl group; R 4 is an alkyl group or an aryl group; R 5 is an alkoxy group or an aryl group; R 6 is an alkoxy group or an aryl group.

[0049] Preferably, R 2When it is aryl, specifically phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 3-bromophenyl, 2-bromophenyl, 4-methylphenyl, 3-methylphenyl, 2-methylphenyl, 4-methoxyphenyl, 2-naphthyl or 1-naphthyl;

[0050] R 3 When it is an alkyl group, it is specifically methyl or ethyl; R 3 When it is an aryl group, specifically phenyl, 4-chlorophenyl, 4-bromophenyl, 3-bromophenyl, 2-bromophenyl, 4-methylphenyl or 4-methoxyphenyl;

[0051] R 4 When it is an alkyl group, it is specifically methyl or ethyl; R 4 When it is an aryl group, specifically phenyl, 4-methoxyphenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 4-chlorophenyl, 4-cyanophenyl, 4-trifluoromethylphenyl, 4-phenylphenyl, 2-naphthyl, 1-naphthyl, pyridyl or thienyl;

[0052] R 5 When it is an alkoxy group, it is specifically methoxy, ethoxy or isopropoxy; the R 5 When it is an aryl group, specifically phenyl, 4-methoxyphenyl, 4-methylphenyl, 4-chlorophenyl, 4-bromophenyl, 2-methylphenyl or 3,5-dimethylphenyl;

[0053] R 6 When it is an alkoxy group, it is specifically methoxy, ethoxy or isopropoxy; the R 6 When it is an aryl group, specifically, it is phenyl, 4-methoxyphenyl, 4-methylphenyl, 4-chlorophenyl, 4-bromophenyl, 2-methylphenyl or 3,5-dimethylphenyl.

[0054] In a second aspect of the present invention, a method for preparing the above-mentioned meta-phosphonylated multi-substituted pyridine compound is provided, comprising the following steps:

[0055] Compound 1 (tertiary olefin amide) and compound 2 (organophosphorus reagent) are added to an organic solvent, and then a promoter (manganese acetate dihydrate) is added, and heated to react to obtain a meta-phosphonylated multi-substituted pyridine compound;

[0056] The structural formula of compound 1 is as follows:

[0057]

[0058] The structural formula of compound 2 is as follows:

[0059]

[0060] The chemical reaction equation is as follows:

[0061]

[0062] Among them, R 1 is alkyl, alkoxy or aryl; R 2 is an aryl group; R 3 is a hydrogen atom, an alkyl group or an aryl group; R 4 is an alkyl group or an aryl group; R 5 is an alkoxy group or an aryl group; R 6 is an alkoxy group or an aryl group.

[0063] Preferably, R 1 When it is an alkyl group, specifically methyl, ethyl or isopropyl; R 1 When it is an alkoxy group, it is specifically tert-butoxy or benzyloxy; R 1 When it is an aryl group, specifically, it is phenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 4-methylphenyl, 4-methoxyphenyl, 4-chlorophenyl, 4-fluorophenyl or 4-nitrophenyl.

[0064] R 2 When it is aryl, specifically phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 3-bromophenyl, 2-bromophenyl, 4-methylphenyl, 3-methylphenyl, 2-methylphenyl, 4-methoxyphenyl, 2-naphthyl or 1-naphthyl;

[0065] R 3 When it is an alkyl group, it is specifically methyl or ethyl; R 3 When it is an aryl group, specifically phenyl, 4-chlorophenyl, 4-bromophenyl, 3-bromophenyl, 2-bromophenyl, 4-methylphenyl or 4-methoxyphenyl;

[0066] R 4 When it is an alkyl group, it is specifically methyl or ethyl; R 4 When it is an aryl group, specifically phenyl, 4-methoxyphenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 4-chlorophenyl, 4-cyanophenyl, 4-trifluoromethylphenyl, 4-phenylphenyl, 2-naphthyl, 1-naphthyl, pyridyl or thienyl;

[0067] R 5 When it is an alkoxy group, it is specifically methoxy, ethoxy or isopropoxy; the R 5 When it is an aryl group, specifically phenyl, 4-methoxyphenyl, 4-methylphenyl, 4-chlorophenyl, 4-bromophenyl, 2-methylphenyl or 3,5-dimethylphenyl;

[0068] R 6 When it is an alkoxy group, it is specifically methoxy, ethoxy or isopropoxy; the R 6When it is an aryl group, specifically, it is phenyl, 4-methoxyphenyl, 4-methylphenyl, 4-chlorophenyl, 4-bromophenyl, 2-methylphenyl or 3,5-dimethylphenyl.

[0069] Preferably, the molar ratio of compound 1, compound 2 and accelerator is 1:(1-2):(2-4), more preferably 1:2:3.

[0070] The organic solvent includes any one of toluene, dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF) and acetic acid (AcOH), and more preferably acetic acid (AcOH).

[0071] Preferably, the amount ratio of compound 1 to the organic solvent is 0.2 mmol:2.0 mL; preferably, the heating reaction temperature is 40-140° C., and the time is 5-20 h, more preferably 100-120° C., and 5-6 h.

[0072] The third technical solution of the present invention: an application of the above-mentioned meta-phosphonylated multi-substituted pyridine compound as an agent for preventing agricultural pests.

[0073] Preferably, the agricultural pests include Spodoptera exigua.

[0074] Example 1

[0075] A method for preparing a meta-phosphonylated multi-substituted pyridine compound (compound of formula IIIaa structure):

[0076] In an air atmosphere, 0.2 mmol of the compound of formula Ia, 0.4 mmol of the compound of formula IIa (diphenylphosphine oxide), Mn(OAc)3·2H2O (0.6 mmol, 3.0 equiv) and 2.0 mL of acetic acid were added to a 10 mL reaction tube, and then the reaction tube was sealed and heated to 110°C in an oil bath for about 5 h. After the reaction was completed, it was cooled to room temperature, 20 mL of saturated NaHCO3 aqueous solution was added to quench the reaction, and it was extracted with ethyl acetate (3×30 mL), and the organic phases were combined and then back-extracted with saturated brine, and then dried and concentrated with anhydrous Na2SO4. The residue was separated by silica gel column chromatography (petroleum ether: ethyl acetate = 2:1) to obtain meta-phosphonylated polysubstituted pyridine compounds (compounds of formula IIIaa structure) with a yield of 95%.

[0077] The chemical reaction equation is as follows:

[0078]

[0079] The characterization data of the compound of formula IIIaa are as follows:

[0080] The compound is a white solid with a melting point of mp: 210-212°C;

[0081] 1 H NMR(500MHz,Chloroform-d)δ8.42(d,J=7.4Hz,1H),7.61(dd,J=11.9,7.6Hz,4H),7.55(d,J=9.9Hz,2H),7.48-7 .40(m,5H),7.39-7.33(m,4H),7.13(t,J=7.3Hz,1H),7.07(t,J=7.5Hz,2H),6.94(d,J=7.4Hz,2H),1.98(s,3H);

[0082] 31 PNMR(202MHz,Chloroform-d)δ24.29;

[0083] 13 C NMR(126MHz,Chloroform-d)δ162.5,156.0(d,J C-P =8.8Hz),150.4(d,J C-P =13.9Hz),140.3,136.1(d,J C-P =3.8Hz),132.3(d,J C-P =105.8Hz),131.68(d,J C-P =13.9Hz),131.65,130.9(d,J C-P =7.6Hz),129.6,129.2,128.7,128.4(d,J C-P =11.3Hz),128.3,127.7,127.5,126.9(d,J C-P =100.8Hz),18.1;

[0084] HRMS (ESI) m / z [M+H] + Calcd.for C 30 H 25 NOP 446.1668; Found 446.1652.

[0085] Embodiments 2 to 11

[0086] The same as Example 1, except that the compound of formula Ia is replaced by an equimolar amount of other types of tertiary enamides.

[0087] Table 1 Preparation of compounds of formula IIIaa using different types of tertiary enamides

[0088]

[0089]

[0090] Example 12

[0091] The same as Example 1, except that the compound of formula Ia is replaced by an equimolar amount of the compound of formula Ib, to obtain meta-phosphonylated polysubstituted pyridine compounds (compounds of formula IIIba structure) with a yield of 59%.

[0092] The chemical reaction equation is as follows:

[0093]

[0094] The characterization data of the compound of formula IIIba are as follows:

[0095] The compound is a white solid, melting point mp: 275-276°C;

[0096] 1 H NMR(500MHz,Chloroform-d)δ8.41(d,J=7.3Hz,1H),7.64-7.53(m,6H),7.45(d,J=6.8Hz,2H),7 .39-7.32(m,4H),7.17-7.12(m,3H),7.07(t,J=6.9Hz,2H),6.92(d,J=7.1Hz,2H),1.98(s,3H);

[0097] 31 PNMR(202MHz,Chloroform-d)δ24.15;

[0098] 19 F NMR(471MHz,Chloroform-d)δ-112.78;

[0099] HRMS (ESI) m / z [M+H] + Calcd.for C 30 H 24 FNOP464.1574;Found 464.1564.

[0100] Example 13

[0101] The same as Example 1, except that the compound of formula Ia is replaced by an equimolar amount of the compound of formula Ic, to obtain meta-phosphonylated polysubstituted pyridine compounds (compounds of formula IIIca structure) with a yield of 61%.

[0102] The chemical reaction equation is as follows:

[0103]

[0104] The characterization data of the compound of formula IIIca are as follows:

[0105] The compound is a white solid with a melting point of mp: 297-299°C;

[0106] 1 H NMR(500MHz,Chloroform-d)δ8.41(d,J=7.3Hz,1H),7.60(dd,J=11.9,7.3Hz,4H),7.50(d,J=8.2Hz,2H),7.47-7 .41(m,4H),7.39-7.33(m,4H),7.14(t,J=7.3Hz,1H),7.07(t,J=7.3Hz,2H),6.91(d,J=7.3Hz,2H),1.97(s,3H);

[0107] 31 PNMR(202MHz,Chloroform-d)δ24.13;

[0108] HRMS (ESI) m / z [M+H] + Calcd.for C 30 H 24 ClNOP 480.1279; Found 480.1290.

[0109] Embodiment 14

[0110] The same as Example 1, except that the compound of formula Ia is replaced by an equimolar amount of the compound of formula Id, to obtain an meta-phosphonylated multi-substituted pyridine compound (compound of formula IIIda structure) with a yield of 65%.

[0111] The chemical reaction equation is as follows:

[0112]

[0113] The characterization data of the compound of formula IIIda are as follows:

[0114] The compound is a white solid with a melting point of mp: 298-299°C;

[0115] 1 H NMR(500MHz,Chloroform-d)δ8.41(d,J=7.3Hz,1H),7.64-7.57(m,6H),7.48-7.42(m,4H),7.39 -7.34(m,4H),7.14(t,J=7.2Hz,1H),7.07(t,J=7.0Hz,2H),6.91(d,J=7.1Hz,2H),1.97(s,3H);

[0116] 31 PNMR(202MHz,Chloroform-d)δ24.12;

[0117] HRMS (ESI) m / z [M+H] + Calcd.for C 30 H 24 BrNOP 524.0773,526.0753; Found524.0781,526.0760.

[0118] Embodiment 15

[0119] The same as Example 1, except that the compound of formula Ia is replaced by an equimolar amount of the compound of formula Ie, to obtain an meta-phosphonylated polysubstituted pyridine compound (compound of formula IIIea structure) with a yield of 90%.

[0120] The chemical reaction equation is as follows:

[0121]

[0122] The characterization data of the compound of formula IIIea are as follows:

[0123] The compound is a white solid with a melting point of mp: 260-261°C;

[0124] 1 H NMR(500MHz,Chloroform-d)δ8.41(d,J=7.3Hz,1H),7.71(s,1H),7.63-7.55(m,5H),7.50-7.44(m,3H ),7.40-7.32(m,5H),7.15(t,J=7.3Hz,1H),7.08(t,J=7.3Hz,2H),6.92(d,J=7.3Hz,2H),1.98(s,3H);

[0125] 31 PNMR(202MHz,Chloroform-d)δ24.06;

[0126] HRMS (ESI) m / z [M+H] + Calcd.for C 30 H 24 BrNOP 524.0773,526.0753; Found524.0784,526.0764.

[0127] Example 16

[0128] The same as Example 1, except that the compound of formula Ia is replaced by an equimolar amount of the compound of formula If, to obtain meta-phosphonylated polysubstituted pyridine compounds (compounds of formula IIIfa structure) with a yield of 78%.

[0129] The chemical reaction equation is as follows:

[0130]

[0131] The characterization data of the compound of formula IIIfa are as follows:

[0132] The compound is a white solid with a melting point of mp: 267-268°C;

[0133] 1 H NMR(500MHz,Chloroform-d)δ8.42(d,J=7.3Hz,1H),7.72(s,1H),7.64-7.54(m,5H),7.47(q,J=7.4Hz,3 H),7.41-7.31(m,5H),7.15(t,J=7.3Hz,1H),7.08(t,J=7.2Hz,2H),6.92(d,J=7.3Hz,2H),1.98(s,3H);

[0134] 31 PNMR(202MHz,Chloroform-d)δ24.06;

[0135] HRMS (ESI) m / z [M+H] + Calcd.for C 30 H 24 BrNOP 524.0773,526.0753; Found524.0782,526.0761.

[0136] Embodiment 17

[0137] The same as Example 1, except that the compound of formula Ia is replaced by an equimolar amount of the compound of formula Ig, to obtain meta-phosphonylated polysubstituted pyridine compounds (compounds of formula IIIga structure) with a yield of 92%.

[0138] The chemical reaction equation is as follows:

[0139]

[0140] The characterization data of the compound of formula IIIga structure are as follows:

[0141] The compound is a white solid with a melting point of mp: 269-270°C;

[0142] 1H NMR(500MHz,Chloroform-d)δ8.40(d,J=7.1Hz,1H),7.61(dd,J=12.0,6.9Hz,4H),7.44(t,J=7.6Hz,4H),7.38-7.33(m,4 H),7.26(d,J=7.3Hz,2H),7.13(t,J=7.1Hz,1H),7.06(t,J=7.0Hz,2H),6.93(d,J=7.2Hz,2H),2.40(s,3H),1.99(s,3H);

[0143] 31 PNMR(202MHz,Chloroform-d)δ24.26;

[0144] HRMS (ESI) m / z [M+H] + Calcd.for C 31 H 27 NOP460.1825; Found 460.1814.

[0145] Embodiment 18

[0146] The same as Example 1, except that the compound of formula Ia is replaced by an equimolar amount of the compound of formula Ih, to obtain an meta-phosphonylated polysubstituted pyridine compound (compound of formula IIIha structure) with a yield of 68%.

[0147] The chemical reaction equation is as follows:

[0148]

[0149] The characterization data of the compound of formula IIIha are as follows:

[0150] The compound is a white solid with a melting point of mp: 268-270°C;

[0151] 1 H NMR(500MHz,Chloroform-d)δ8.41(d,J=7.4Hz,1H),7.71-7.55(m,4H),7.44(s,2H),7.36(s,4H),7 .31-7.24(m,3H),7.21(d,J=7.5Hz,1H),7.15-6.97(m,4H),6.82(s,1H),2.12(s,3H),1.76(s,3H);

[0152] 31 PNMR(202MHz,Chloroform-d)δ24.49;

[0153] HRMS (ESI) m / z [M+H] + Calcd.for C 31 H 27 NOP460.1825; Found 460.1815.

[0154] Embodiment 19

[0155] The same as Example 1, except that the compound of formula Ia is replaced by an equimolar amount of the compound of formula Ii, to obtain meta-phosphonylated polysubstituted pyridine compounds (compounds of formula IIIia structure) with a yield of 87%.

[0156] The chemical reaction equation is as follows:

[0157]

[0158] The characterization data of the compound of formula IIIia are as follows:

[0159] The compound is a white solid with a melting point of mp: 217-219°C;

[0160] 1 H NMR(500MHz,Chloroform-d)δ8.39(d,J=7.3Hz,1H),7.60(dd,J=11.9,7.1Hz,4H),7.52(d,J=8.2Hz,2H),7.43(t,J=7.1Hz,2H),7.3 7-7.32(m,4H),7.12(t,J=7.2Hz,1H),7.06(t,J=7.1Hz,2H),6.97(d,J=7.4Hz,2H),6.92(d,J=7.2Hz,2H),3.83(s,3H),2.00(s,3H);

[0161] 31 PNMR(202MHz,Chloroform-d)δ24.21;

[0162] HRMS (ESI) m / z [M+H] + Calcd.for C 31 H 27 NO2P 476.1774; Found 476.1783.

[0163] Embodiment 20

[0164] The same as Example 1, except that the compound of formula Ia is replaced by an equimolar amount of the compound of formula Ij, to obtain an meta-phosphonylated polysubstituted pyridine compound (compound of formula IIIja structure) with a yield of 70%.

[0165] The chemical reaction equation is as follows:

[0166]

[0167] The characterization data of the compound of formula IIIja are as follows:

[0168] The compound is a white solid with a melting point of mp: 270-272°C;

[0169] 1 H NMR(500MHz,Chloroform-d)δ8.47(d,J=7.3Hz,1H),8.05(s,1H),7.94(d,J=7.9Hz,1H),7.91-7.87(m,2H),7.69(d,J=8.4Hz,1H),7.63(dd,J=12.1,7. 2Hz,4H),7.55-7.50(m,2H),7.46(t,J=7.1Hz,2H),7.40-7.35(m,4H),7.15 (t,J=7.2Hz,1H),7.09(t,J=7.1Hz,2H),6.96(d,J=7.1Hz,2H),2.05(s,3H);

[0170] 31 PNMR(202MHz,Chloroform-d)δ24.23;

[0171] HRMS (ESI) m / z [M+H] + Calcd.for C 34 H 27 NOP496.1825; Found 496.18233.

[0172] Embodiment 21

[0173] The same as Example 1, except that the compound of formula Ia is replaced by an equimolar amount of the compound of formula Ik to obtain an meta-phosphonylated polysubstituted pyridine compound (compound of formula IIIka structure) with a yield of 56%.

[0174] The chemical reaction equation is as follows:

[0175]

[0176] The characterization data of the compound of formula IIIka structure are as follows:

[0177] The compound is a white solid with a melting point of mp: 216-217°C;

[0178] 1H NMR(500MHz,Chloroform-d)δ8.56(d,J=7.7Hz,1H),8.05(d,J=7.2Hz,2H),7.73(d,J=2.9Hz,1H),7.63( dd,J=12.0,7.5Hz,4H),7.50-7.45(m,3H),7.42(t,J=7.4Hz,2H),7.37-7.30(m,6H),7.19-7.11(m,3H);

[0179] 31 PNMR(202MHz,Chloroform-d)δ24.88;

[0180] HRMS (ESI) m / z [M+H] + Calcd.for C 29 H 23 NOP 432.1512; Found 432.1502.

[0181] Embodiment 22

[0182] The same as Example 1, except that the compound of formula Ia is replaced by an equimolar amount of the compound of formula Il, to obtain an meta-phosphonylated polysubstituted pyridine compound (compound of formula IIIla structure) with a yield of 67%.

[0183] The chemical reaction equation is as follows:

[0184]

[0185] The characterization data of the compound of formula IIIla structure are as follows:

[0186] The compound is a white solid with a melting point of mp: 233-235°C;

[0187] 1 H NMR(500MHz,Chloroform-d)δ8.38(d,J=7.4Hz,1H),7.67-7.57(m,4H),7.51-7.41(m,7H),7.40-7.33(m,4H),7 .13(t,J=7.1Hz,1H),7.04(t,J=7.0Hz,2H),6.96(d,J=7.3Hz,2H),2.44(q,J=7.2Hz,2H),0.66(t,J=7.1Hz,3H);

[0188] 31 PNMR(202MHz,Chloroform-d)δ24.41;

[0189] HRMS (ESI) m / z [M+H] + Calcd.for C 31 H 27 NOP460.1825; Found 460.1836.

[0190] Embodiment 23

[0191] The same as Example 1, except that the compound of formula Ia is replaced by an equimolar amount of the compound of formula Im, to obtain meta-phosphonylated polysubstituted pyridine compounds (compounds of formula IIIma structure) with a yield of 50%.

[0192] The chemical reaction equation is as follows:

[0193]

[0194] The characterization data of the compound of formula IIIma structure are as follows:

[0195] The compound is a white solid with a melting point of mp: 233-234°C;

[0196] 1 H NMR(500MHz,Chloroform-d)δ8.58(d,J=7.5Hz,1H),7.65(dd,J=12.0,7.4Hz,4H),7.43(t,J=7.3Hz,2H),7.38-7 .32(m,4H),7.28(d,J=10.0Hz,2H),7.21-7.13(m,3H),6.98-6.90(m,3H),6.88-6.83(m,1H),6.81-6.74(m,6H);

[0197] 31 PNMR(202MHz,Chloroform-d)δ24.68;

[0198] HRMS (ESI) m / z [M+H] + Calcd.for C 35 H 27 NOP 508.1825; Found 508.1817.

[0199] Embodiment 24

[0200] The same as Example 1, except that the compound of formula Ia is replaced by an equimolar amount of the compound of formula In, to obtain an meta-phosphonylated multi-substituted pyridine compound (compound of formula IIIna structure) with a yield of 82%.

[0201] The chemical reaction equation is as follows:

[0202]

[0203] The characterization data of the compound of formula IIIna structure are as follows:

[0204] The compound is a white solid with a melting point of mp: 210-211°C;

[0205] 1 H NMR(500MHz,Chloroform-d)δ8.40(d,J=7.4Hz,1H),7.62(dd,J=11.9,7.5Hz,4H),7.54(d,J=8.2Hz,2H),7. 47-7.40(m,5H),7.39-7.33(m,4H),6.86(d,J=8.1Hz,2H),6.59(d,J=8.1Hz,2H),3.75(s,3H),2.00(s,3H);

[0206] 31 PNMR(202MHz,Chloroform-d)δ24.17;

[0207] HRMS (ESI) m / z [M+H] + Calcd.for C 31 H 27 NO2P 476.1774; Found 476.1782.

[0208] Embodiment 25

[0209] The same as Example 1, except that the compound of formula Ia is replaced by an equimolar amount of the compound of formula Io, to obtain an meta-phosphonylated multi-substituted pyridine compound (compound of formula IIIoa structure) with a yield of 89%.

[0210] The chemical reaction equation is as follows:

[0211]

[0212] The characterization data of the compound of formula IIIoa structure are as follows:

[0213] The compound is a white solid with a melting point of mp: 137-139°C;

[0214] 1H NMR(500MHz,Chloroform-d)δ8.52(d,J=7.3Hz,1H),7.65-7.57(m,4H),7.56-7.52(m,2H),7.50-7.41(m,5H),7.40-7.34(m,4H),7. 08(td,J=7.5,1.4Hz,1H),6.96(d,J=7.5Hz,1H),6.86(td,J=7.6,1.2Hz,1H),6.68(dd,J=7.6,1.3Hz,1H),1.91(s,3H),1.87(s,3H);

[0215] 31 PNMR(202MHz,Chloroform-d)δ23.54;

[0216] HRMS (ESI) m / z [M+H] + Calcd.for C 31 H 27 NOP460.1825; Found 460.1816.

[0217] Embodiment 26

[0218] The same as Example 1, except that the compound of formula Ia is replaced by an equimolar amount of the compound of formula Ip, to obtain meta-phosphonylated polysubstituted pyridine compounds (compounds of formula IIIpa structure) with a yield of 80%.

[0219] The chemical reaction equation is as follows:

[0220]

[0221] The characterization data of the compound of formula IIIpa are as follows:

[0222] The compound is a white solid with a melting point of mp: 253-254°C;

[0223] 1 H NMR(500MHz,Chloroform-d)δ8.43(d,J=7.4Hz,1H),7.68-7.62(m,2H),7.61-7.56(m,2H),7.56-7.52(m,2H),7.48-7.41(m,5H) ,7.40-7.32(m,4H),7.02(t,J=7.5Hz,1H),6.93(d,J=7.5Hz,1H),6.85(d,J=7.5Hz,1H),6.59(s,1H),2.09(s,3H),1.99(s,3H);

[0224] 31PNMR(202MHz,Chloroform-d)δ24.18;

[0225] HRMS (ESI) m / z [M+H] + Calcd.for C 31 H 27 NOP460.1825; Found 460.1815.

[0226] Embodiment 27

[0227] The same as Example 1, except that the compound of formula Ia is replaced by an equimolar amount of the compound of formula Iq, to ​​obtain an meta-phosphonylated polysubstituted pyridine compound (compound of formula IIIqa structure) with a yield of 68%.

[0228] The chemical reaction equation is as follows:

[0229]

[0230] The characterization data of the compound of formula IIIqa are as follows:

[0231] The compound is a white solid with a melting point of mp: 228-230°C;

[0232] 1 H NMR(500MHz,Chloroform-d)δ8.42(d,J=7.4Hz,1H),7.64-7.58(m,4H),7.56-7.52(m,2H),7.48-7.41(m, 5H),7.36(td,J=7.6,3.0Hz,4H),6.86(d,J=7.7Hz,2H),6.81(d,J=7.8Hz,2H),2.26(s,3H),2.00(s,3H);

[0233] 31 PNMR(202MHz,Chloroform-d)δ24.28;

[0234] HRMS (ESI) m / z [M+H] + Calcd.for C 31 H 27 NOP460.1825; Found 460.1816.

[0235] Embodiment 28

[0236] The same as Example 1, except that the compound of formula Ia is replaced by an equimolar amount of the compound of formula Ir, to obtain meta-phosphonylated polysubstituted pyridine compounds (compounds of formula IIIra structure) with a yield of 58%.

[0237] The chemical reaction equation is as follows:

[0238]

[0239] The characterization data of the compound of formula IIIra structure are as follows:

[0240] The compound is a white solid with a melting point of mp: 276-278°C;

[0241] 1 H NMR(500MHz,Chloroform-d)δ8.40(d,J=7.3Hz,1H),7.61(dd,J=11.9,7.4Hz,4H),7.52(d,J=7.5Hz, 2H),7.50-7.40(m,5H),7.40-7.35(m,4H),7.03(d,J=7.7Hz,2H),6.87(d,J=7.9Hz,2H),1.97(s,3H);

[0242] 31 P NMR(202MHz,Chloroform-d)δ24.05;

[0243] HRMS (ESI) m / z [M+H] + Calcd.for C 30 H 24 ClNOP 480.1279; Found 480.1290.

[0244] Embodiment 29

[0245] The same as Example 1, except that the compound of formula Ia is replaced by an equimolar amount of the compound of formula Is, to obtain an meta-phosphonylated multi-substituted pyridine compound (compound of formula IIIsa structure) with a yield of 53%.

[0246] The chemical reaction equation is as follows:

[0247]

[0248] The characterization data of the compound of formula IIIsa structure are as follows:

[0249] The compound is a white solid with a melting point of mp: 213-215°C;

[0250] 1H NMR(500MHz,Chloroform-d)δ8.38(d,J=7.3Hz,1H),7.61(dd,J=12.0,7.2Hz,4H ),7.52(q,J=7.3Hz,4H),7.47-7.37(m,9H),7.08(d,J=7.5Hz,2H),1.97(s,3H);

[0251] 31 PNMR(202MHz,Chloroform-d)δ24.09;

[0252] HRMS (ESI) m / z [M+H] + Calcd.for C 31 H 24 N2OP 471.1621; Found 471.1629.

[0253] Embodiment 30

[0254] The same as Example 1, except that the compound of formula Ia is replaced by an equimolar amount of the compound of formula It, to obtain an meta-phosphonylated multi-substituted pyridine compound (compound of formula IIIta structure) with a yield of 57%.

[0255] The chemical reaction equation is as follows:

[0256]

[0257] The characterization data of the compound of formula IIIta structure are as follows:

[0258] The compound is a white solid with a melting point of mp: 265-267°C;

[0259] 1 H NMR(500MHz,Chloroform-d)δ8.43(d,J=7.4Hz,1H),7.61(dd,J=11.9,7.5Hz,4H),7.54(d,J=7.4Hz, 2H),7.50-7.42(m,5H),7.40-7.35(m,4H),7.32(d,J=7.6Hz,2H),7.08(d,J=7.8Hz,2H),1.98(s,3H);

[0260] 31 P NMR(202MHz,Chloroform-d)δ23.83;

[0261] 19 F NMR(471MHz,Chloroform-d)δ-62.86;

[0262] HRMS (ESI) m / z [M+H] + Calcd.for C 31 H 24 F3NOP 514.1542; Found 514.1531.

[0263] Embodiment 31

[0264] The same as Example 1, except that the compound of formula Ia is replaced by an equimolar amount of the compound of formula Iu, to obtain an meta-phosphonylated multi-substituted pyridine compound (compound of formula IIIua structure) with a yield of 65%.

[0265] The chemical reaction equation is as follows:

[0266]

[0267] The characterization data of the compound of formula IIIua are as follows:

[0268] The compound is a white solid with a melting point of mp: 166-168°C;

[0269] 1 H NMR(500MHz,Chloroform-d)δ8.47(d,J=7.4Hz,1H),7.65(d,J=7.5Hz,2H),7.63(d,J=7.6Hz,2H),7.57(d,J=6.8Hz,2H ),7.54-7.51(m,2H),7.49-7.42(m,7H),7.39-7.32(m,5H),7.27(d,J=7.8Hz,2H),7.02(d,J=7.9Hz,2H),2.05(s,3H);

[0270] 31 PNMR(202MHz,Chloroform-d)δ23.94;

[0271] HRMS (ESI) m / z [M+H] + Calcd.for C 36 H 29 NOP 522.1981; Found 522.1990.

[0272] Embodiment 32

[0273] The same as Example 1, except that the compound of formula Ia is replaced by an equimolar amount of the compound of formula Iv, to obtain an meta-phosphonylated multi-substituted pyridine compound (compound of formula IIIva structure) with a yield of 79%.

[0274] The chemical reaction equation is as follows:

[0275]

[0276] The characterization data of the compound of formula IIIva are as follows:

[0277] The compound is a white solid with a melting point of mp: 207-209°C;

[0278] 1 H NMR(500MHz,Chloroform-d)δ8.65(d,J=7.3Hz,1H),7.72(dd,J=11.7,7.3Hz,2H),7.64-7.57(m,4H),7.50-7.44(m,3H),7.44-7 .38(m,3H),7.37-7.31(m,3H),7.30-7.22(m,3H),7.12(d,J=8.0Hz,1H),6.94(t,J=7.2Hz,1H),6.87-6.81(m,2H),1.88(s,3H);

[0279] 31 PNMR(202MHz,Chloroform-d)δ23.88;

[0280] HRMS (ESI) m / z [M+H] + Calcd.for C 34 H 27 NOP496.1825; Found 496.1833.

[0281] Embodiment 33

[0282] The same as Example 1, except that the compound of formula Ia is replaced by an equimolar amount of the compound of formula Iw, to obtain an meta-phosphonylated polysubstituted pyridine compound (compound of formula IIIwa structure) with a yield of 90%.

[0283] The chemical reaction equation is as follows:

[0284]

[0285] The characterization data of the compound of formula IIIwa structure are as follows:

[0286] The compound is a white solid with a melting point of mp: 275-277°C;

[0287] 1H NMR(500MHz,Chloroform-d)δ8.39(d,J=7.4Hz,1H),8.37-8.33(m,2H),7.62(ddd,J=12. 0,8.1,1.4Hz,4H),7.55-7.48(m,4H),7.49-7.38(m,7H),6.91-6.86(m,2H),1.97(s,3H);

[0288] 31 PNMR(202MHz,Chloroform-d)δ24.21;

[0289] HRMS (ESI) m / z [M+H] + Calcd.for C 29 H 24 N2OP 447.1621; Found 447.1629.

[0290] Embodiment 34

[0291] The same as Example 1, except that the compound of formula Ia is replaced by an equimolar amount of the compound of formula Ix, to obtain an meta-phosphonylated multi-substituted pyridine compound (compound of formula IIIxa structure) with a yield of 50%.

[0292] The chemical reaction equation is as follows:

[0293]

[0294] The characterization data of the compound of formula IIIxa are as follows:

[0295] The compound is a white solid with a melting point of mp: 227-229°C;

[0296] 1 H NMR(500MHz,Chloroform-d)δ8.43(d,J=7.4Hz,1H),7.68-7.62(m,4H),7.54(d,J=7.3Hz,2H),7.50-7.43( m,5H),7.42-7.37(m,4H),7.17(d,J=4.8Hz,1H),6.91(d,J=3.3Hz,1H),6.82(t,J=3.9Hz,1H),2.13(s,3H);

[0297] 31 PNMR(202MHz,Chloroform-d)δ24.69;

[0298] HRMS (ESI) m / z [M+H] + Calcd.for C28 H 23 NOPS 452.1232; Found 452.1223.

[0299] Embodiment 35

[0300] The same as Example 1, except that the compound of formula Ia is replaced by an equimolar amount of the compound of formula Iy, to obtain an meta-phosphonylated multi-substituted pyridine compound (compound of formula IIIya structure) with a yield of 69%.

[0301] The chemical reaction equation is as follows:

[0302]

[0303] The characterization data of the compound of formula IIIya are as follows:

[0304] The compound is a white solid with a melting point of mp: 130-132°C;

[0305] 1 H NMR (400MHz, Chloroform-d) δ8.02(d,J=7.5Hz,1H),7.71(dd,J=12.0,7.6Hz,4H),7.58(t,J=7.9Hz,2H),7.54-7.40(m,9H),2.51(s,3H),2.28(s,3H);

[0306] 31 PNMR(162MHz,Chloroform-d)δ29.88;

[0307] HRMS (ESI) m / z [M+H] + Calcd.for C 25 H 23 NOP 384.1512; Found 384.1523.

[0308] Embodiment 36

[0309] The same as Example 1, except that the compound of formula IIa (diphenylphosphine oxide) is replaced by an equimolar amount of the compound of formula IIb to obtain an meta-phosphonylated polysubstituted pyridine compound (compound of formula IIIab structure) with a yield of 88%.

[0310] The chemical reaction equation is as follows:

[0311]

[0312] The characterization data of the compound of formula IIIab are as follows:

[0313] The compound is a white solid with a melting point of mp: 173-175°C;

[0314] 1 H NMR(500MHz,Chloroform-d)δ8.43(d,J=7.4Hz,1H),7.56-7.50(m,3H),7.50-7.42(m,5H),7.40(dd,J=8.5 ,5.9Hz,1H),7.18-7.07(m,3H),6.94-6.90(m,2H),6.86(dd,J=8.7,2.3Hz,4H),3.82(s,6H),1.96(s,3H);

[0315] 31 P NMR(202MHz,Chloroform-d)δ24.55;

[0316] HRMS (ESI) m / z [M+H] + Calcd.for C 32 H 29 NO3P 506.1880; Found 506.1892.

[0317] Embodiment 37

[0318] The same as Example 1, except that the compound of formula IIa (diphenylphosphine oxide) is replaced by an equimolar amount of the compound of formula IIc to obtain an meta-phosphonylated polysubstituted pyridine compound (compound of formula IIIac structure) with a yield of 78%.

[0319] The chemical reaction equation is as follows:

[0320]

[0321] The characterization data of the compound of formula IIIac are as follows:

[0322] The compound is a white solid with a melting point of mp: 208-210°C;

[0323] 1 H NMR(500MHz,Chloroform-d)δ8.41(d,J=7.4Hz,1H),7.56-7.52(m,2H),7.50-7.42(m,6H),7.42- 7.38(m,1H),7.19-7.10(m,5H),7.10-7.04(m,2H),6.95-6.89(m,2H),2.36(s,6H),1.97(s,3H);

[0324] 31PNMR(202MHz,Chloroform-d)δ24.79;

[0325] HRMS (ESI) m / z [M+H] + Calcd.for C 32 H 29 NOP 474.1981; Found 474.1974.

[0326] Embodiment 38

[0327] The same as Example 1, except that the compound of formula IIa (diphenylphosphine oxide) is replaced by an equimolar amount of the compound of formula IId to obtain an meta-phosphonylated polysubstituted pyridine compound (compound of formula IIIad structure) with a yield of 80%.

[0328] The chemical reaction equation is as follows:

[0329]

[0330] The characterization data of the compound of formula IIIad are as follows:

[0331] The compound is a white solid with a melting point of mp: 233-234°C;

[0332] 1 H NMR(500MHz,Chloroform-d)δ8.43(d,J=7.6Hz,1H),7.57-7.52(m,3H),7.52-7.49(m,3H),7.48-7.45(m,2H),7.45- 7.41(m,1H),7.35(dd,J=8.5,2.4Hz,4H),7.21-7.16(m,1H),7.12(t,J=7.5Hz,2H),6.96-6.91(m,2H),1.99(s,3H);

[0333] 31 PNMR(202MHz,Chloroform-d)δ23.01;

[0334] HRMS (ESI) m / z [M+H] + Calcd.for C 30 H 23 Cl2NOP 514.0889,516.0859; Found514.0880,516.0851.

[0335] Embodiment 39

[0336] The same as Example 1, except that the compound of formula IIa (diphenylphosphine oxide) is replaced by an equimolar amount of the compound of formula IIe to obtain an meta-phosphonylated polysubstituted pyridine compound (compound of formula IIIae structure) with a yield of 82%.

[0337] The chemical reaction equation is as follows:

[0338]

[0339] The characterization data of the compound of formula IIIae are as follows:

[0340] The compound is a white solid with a melting point of mp: 236-238°C;

[0341] 1 H NMR(500MHz,Chloroform-d)δ8.43(d,J=7.5Hz,1H),7.57-7.53(m,2H),7.51(dd,J=8.4,2.5Hz ,4H),7.49-7.40(m,7H),7.23-7.16(m,1H),7.15-7.09(m,2H),6.95-6.90(m,2H),1.99(s,3H);

[0342] 31 PNMR(202MHz,Chloroform-d)δ23.27;

[0343] HRMS (ESI) m / z [M+H] + Calcd.for C 30 H 23 Br2NOP 601.9879,603.9858; Found601.9869,603.9849.

[0344] Embodiment 40

[0345] The same as Example 1, except that the compound of formula IIa (diphenylphosphine oxide) is replaced by an equimolar amount of the compound of formula IIf to obtain an meta-phosphonylated polysubstituted pyridine compound (compound of formula IIIaf structure) with a yield of 80%.

[0346] The chemical reaction equation is as follows:

[0347]

[0348] The characterization data of the compound of formula IIIaf are as follows:

[0349] The compound is a white solid with a melting point of mp: 153-155°C;

[0350] 1H NMR(500MHz,Chloroform-d)δ8.56(d,J=7.3Hz,1H),7.61-7.56(m,2H),7.48-7.44(m,2H),7.43-7.39(m,1H),7.36(tt,J=7.5 ,1.6Hz,2H),7.23(dd,J=7.7,4.2Hz,2H),7.16-7.11(m,1H),7.09-6.99(m,6H),6.89-6.85(m,2H),2.46(s,6H),1.98(s,3H);

[0351] 31 PNMR(202MHz,Chloroform-d)δ31.57;

[0352] HRMS (ESI) m / z [M+H] + Calcd.for C 32 H 29 NOP 474.1981; Found 474.1992.

[0353] Embodiment 41

[0354] The same as Example 1, except that the compound of formula IIa (diphenylphosphine oxide) is replaced by an equimolar amount of the compound of formula IIg to obtain an meta-phosphonylated polysubstituted pyridine compound (compound of formula IIIag structure) with a yield of 90%.

[0355] The chemical reaction equation is as follows:

[0356]

[0357] The characterization data of the compound of formula IIIag structure are as follows:

[0358] The compound is a white solid with a melting point of mp: 233-234°C;

[0359] 1 H NMR(500MHz,Chloroform-d)δ8.45(d,J=7.3Hz,1H),7.58-7.53(m,2H),7.48-7.39(m,3H),7.20(d, J=12.2Hz,4H),7.16-7.11(m,1H),7.09-7.04(m,4H),6.94-6.88(m,2H),2.27(s,12H),1.98(s,3H);

[0360] 31 PNMR(202MHz,Chloroform-d)δ24.60;

[0361] HRMS (ESI) m / z [M+H] + Calcd.for C 34 H 33 NOP 502.2294; Found 502.2283.

[0362] Embodiment 42

[0363] The same as Example 1, except that the compound of formula IIa (diphenylphosphine oxide) is replaced by an equimolar amount of the compound of formula IIh to obtain an meta-phosphonylated polysubstituted pyridine compound (compound of formula IIIah structure) with a yield of 60%.

[0364] The chemical reaction equation is as follows:

[0365]

[0366] The characterization data of the compound of formula IIIah structure are as follows:

[0367] The compound is a white solid with a melting point of mp: 140-142°C;

[0368] 1 H NMR(500MHz,Chloroform-d)δ9.17(d,J=6.1Hz,1H),7.53(d,J=7.1Hz,2H),7.47-7.43(m,2H),7.40(t,J=7.1Hz,2H),7.34-7.21(m,6H),7 .12(d,J=7.7Hz,1H),7.09-7.03(m,1H),6.63(d,J=7.6Hz,1H),4.08-3.98(m,1H),3.96-3.87(m,1H),1.91(s,3H),1.27(t,J=7.0Hz,3H);

[0369] 31 PNMR(202MHz,Chloroform-d)δ29.05;

[0370] HRMS (ESI) m / z [M+H] + Calcd.for C 26 H 25 NO2P 414.1617; Found 414.1625.

[0371] Embodiment 43

[0372] The same as Example 1, except that the compound of formula IIa (diphenylphosphine oxide) is replaced by an equimolar amount of the compound of formula IIi to obtain an meta-phosphonylated polysubstituted pyridine compound (compound of formula IIIai structure) with a yield of 86%.

[0373] The chemical reaction equation is as follows:

[0374]

[0375] The characterization data of the compound of formula IIIai are as follows:

[0376] The compound is a colorless oily liquid;

[0377] 1 H NMR(500MHz,Chloroform-d)δ9.04(d,J=6.8Hz,1H),7.54-7.50(m,2H),7.47-7.37(m,6H),7 .28-7.22(m,2H),3.98-3.88(m,2H),3.88-3.78(m,2H),1.99(s,3H),1.17(t,J=7.0Hz,6H);

[0378] 31 PNMR(202MHz,Chloroform-d)δ15.73;

[0379] HRMS (ESI) m / z [M+H] + Calcd.for C 22 H 25 NO3P 382.1567; Found 382.1576.

[0380] Effect Example 1

[0381] The insecticidal biological activity of the meta-phosphonylated multi-substituted pyridine compounds prepared in the examples was tested, and the testing method was as follows:

[0382] (1) Insect source type: 3rd instar larvae of Spodoptera exigua;

[0383] (2) Experimental instruments: balance, incubator, insect culture plate, culture dish;

[0384] (3) Test method: Toxicity test of stomach poison, unlimited feeding method;

[0385] (4) Control drugs: pyrimidinephos and triazophos;

[0386] (5) The meta-phosphonylated polysubstituted pyridine compounds prepared in the examples and the control agents (pyrimidinphos, triazophos) were prepared into a standard 2000 mg / L solution (solvent: acetone), and diluted 100 times (concentration: 20 mg / L) to obtain the test agent solution. The 3rd-instar beet armyworm larvae were starved for 5 hours, and 20 healthy 3rd-instar beet armyworm larvae were selected for each group; an appropriate amount of feed was evenly distributed in the intervals of each insect plate, and 10.00 μL of the test agent solution with a concentration of 20 mg / L was injected into each interval with a micropipette, and two groups of each agent were tested in parallel; the 20 selected test insects were evenly distributed in the intervals of each insect plate, one in each interval, and the insect plates were covered with disinfected toilet paper and sprayed with an appropriate amount of distilled water for moisture; at the same time, a blank control test was performed, and the insect plates were placed in a light incubator at 25°C for moisture, and the death of beet armyworm larvae was counted at 24h, 48h, and 72h. The death standard was the immobility of the insect body or the inability to lay and crawl normally. The number of dead insects was recorded, and the death ratio was calculated.

[0387] (6) The experimental results are shown in Table 2.

[0388] Table 2 Insecticidal activity (concentration: 20 mg / L, lethality / %)

[0389]

[0390]

[0391] As can be seen from Table 2, some of the newly prepared meta-phosphonylated polysubstituted pyridine compounds have certain insecticidal activity against beet armyworm larvae at a concentration of 20 mg / L, and the compounds of formula IIIba, IIIia, IIIna, IIIta, IIIwa, IIIxa, IIIab, IIIad, IIIah, and IIIai have a lethality against the 3rd instar beet armyworm larvae at 72 hours that is close to that of the control agents pyrimidinphos and triazophos. The results also show that the lethality of the compounds provided by the present invention against the 3rd instar beet armyworm larvae is positively correlated with the duration of medication.

[0392] The embodiments described above are only descriptions of the preferred modes of the present invention, and are not intended to limit the scope of the present invention. Without departing from the design spirit of the present invention, various modifications and improvements made to the technical solutions of the present invention by ordinary technicians in this field should all fall within the protection scope determined by the claims of the present invention.

Claims

1. A meta-phosphonylated polysubstituted pyridine compound, It is characterized in that The structural formula is shown in formula (1): Among them, R 2 is an aryl group; R 3 is a hydrogen atom, an alkyl group or an aryl group; R 4 is an alkyl group or an aryl group; R 5 is an alkoxy group or an aryl group; R 6 is an alkoxy group or an aryl group.

2. The meta-phosphonylated polysubstituted pyridine compound according to claim 1, It is characterized in that The R 2 When it is aryl, specifically phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 3-bromophenyl, 2-bromophenyl, 4-methylphenyl, 3-methylphenyl, 2-methylphenyl, 4-methoxyphenyl, 2-naphthyl or 1-naphthyl; The R 3 When it is an alkyl group, it is specifically a methyl group or an ethyl group; 3 When it is an aryl group, specifically phenyl, 4-chlorophenyl, 4-bromophenyl, 3-bromophenyl, 2-bromophenyl, 4-methylphenyl or 4-methoxyphenyl; The R 4 When it is an alkyl group, it is specifically a methyl group or an ethyl group; 4 When it is an aryl group, specifically phenyl, 4-methoxyphenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 4-chlorophenyl, 4-cyanophenyl, 4-trifluoromethylphenyl, 4-phenylphenyl, 2-naphthyl, 1-naphthyl, pyridyl or thienyl; The R 5 When it is an alkoxy group, it is specifically methoxy, ethoxy or isopropoxy; the R 5 When it is an aryl group, specifically phenyl, 4-methoxyphenyl, 4-methylphenyl, 4-chlorophenyl, 4-bromophenyl, 2-methylphenyl or 3,5-dimethylphenyl; The R 6 When it is an alkoxy group, it is specifically methoxy, ethoxy or isopropoxy; the R 6 When it is an aryl group, specifically, it is phenyl, 4-methoxyphenyl, 4-methylphenyl, 4-chlorophenyl, 4-bromophenyl, 2-methylphenyl or 3,5-dimethylphenyl.

3. A method for preparing the meta-phosphonylated multi-substituted pyridine compound according to any one of claims 1 to 2, It is characterized in that The following steps are involved: Adding compound 1 and compound 2 into an organic solvent, then adding a promoter, and heating for reaction to obtain the meta-phosphonylated multi-substituted pyridine compound; The structural formula of the compound 1 is as follows: The structural formula of the compound 2 is as follows: Among them, R 1 is alkyl, alkoxy or aryl; R 2 is an aryl group; R 3 is a hydrogen atom, an alkyl group or an aryl group; R 4 is an alkyl group or an aryl group; R 5 and R 6 All are alkoxy or aryl.

4. The preparation method according to claim 3, It is characterized in that The R 1 When it is an alkyl group, it is specifically methyl, ethyl or isopropyl; The R 1 When it is an alkoxy group, it is specifically tert-butoxy or benzyloxy; The R 1 When it is an aryl group, specifically, it is phenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 4-methylphenyl, 4-methoxyphenyl, 4-chlorophenyl, 4-fluorophenyl or 4-nitrophenyl.

5. The preparation method according to claim 3, It is characterized in that The molar ratio of the compound 1, the compound 2 and the accelerator is 1:(1-2):(2-4); The organic solvent includes any one of toluene, dimethyl sulfoxide, N,N-dimethylformamide and acetic acid; The accelerator includes manganese acetate.

6. The preparation method according to claim 3, It is characterized in that The heating reaction is carried out at a temperature of 40 to 140° C. and for a time of 5 to 20 hours.

7. Use of the meta-phosphonylated multi-substituted pyridine compound according to any one of claims 1 to 2 as an agent for preventing agricultural pests.

8. The use according to claim 7, It is characterized in that The agricultural pests include Spodoptera exigua.

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