A preparation method of meta-phosphonylated polysubstituted pyridine compounds

Abstract

The present invention discloses a method for preparing meta-phosphonylated polysubstituted pyridine compounds, belonging to the technical field of organic synthesis. 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. Tertiary olefin amide and organophosphorus reagent are used as basic raw materials, and manganese acetate is used as a promoter (using conventional reaction reagents, solvents, and promoters). Through an intramolecular free radical cascade reaction, meta-phosphonylated polysubstituted pyridine compounds can be obtained in one step with high efficiency and yield of up to 95%. In addition, the reaction raw materials of the present invention are cheap and readily available, have high atom economy, wide substrate universality, and strong operability. 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.

Description

Technical Field

[0001] The present 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] Pyridines are a very important class of organic compounds, found widely in natural products, pharmaceutical molecules, and functional materials. Phosphonylated pyridines are a subclass with unique structures and properties. The introduction of phosphorus atoms endows these compounds with a wide range of physiological activities, making them important in fields such as medicine and pesticides. After reduction, the phosphorus-oxygen double bond forms a common nitrogen-phosphorus ligand, widely used in transition-metal-catalyzed organic syntheses. Furthermore, the phosphonyl group can serve as a directing group or activating functional group, allowing further derivatization to produce a variety of nitrogen heterocyclic compounds.

[0003] People have long been seeking simple and efficient methods for preparing phosphonylated pyridine compounds. However, due to the inherent electronic properties of the pyridine ring, most 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 existing technology 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 inexpensive and readily available chemical reagents under mild reaction conditions to prepare meta-phosphonylated pyridine compounds 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 an aryl group, 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, specifically a methyl group or an ethyl group; the R 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, specifically a methyl group or an ethyl group; the 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;

[0012] The R 5 When it is an alkoxy group, 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, 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 polysubstituted pyridine compound, comprising the following steps:

[0015] Compound 1 (tertiary ene amide) and compound 2 (organophosphorus reagent) are added to an organic solvent, and then a promoter is added, and heated to react 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 an alkyl group, an alkoxy group or an aryl group; 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, 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 an aryl group, 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, specifically a methyl group or an ethyl group; the R 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, specifically a methyl group or an ethyl group; the 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;

[0027] The R 5 When it is an alkoxy group, 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, 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 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 the time is 5-6 h.

[0033] The third technical solution of the present invention: an application of the above-mentioned meta-phosphonylated polysubstituted 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, or expensive precious metal catalysts. Tertiary ene amide and organophosphorus reagent are used as basic raw materials, and manganese acetate is used as a promoter (using conventional reaction reagents, solvents, and promoters). Through the intramolecular free radical cascade reaction, meta-phosphonylated polysubstituted pyridine compounds can be efficiently obtained in one step with a yield of up to 95%. In addition, the reaction raw materials of the present invention are cheap and readily available, the atom economy is high, the substrate is widely applicable, 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, thus avoiding tedious 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 rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

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

[0042] Unless otherwise indicated, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art. Although only preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein may also be used in the practice 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 any conflict with any incorporated document, the contents 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 described herein without departing from the scope or spirit of the invention. Other embodiments will be apparent to those skilled in the art from the description of the invention. The description and examples are intended to be 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 polysubstituted 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 an aryl group, 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, 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, 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, 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, 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, the present invention provides a method for preparing the above-mentioned meta-phosphonylated polysubstituted pyridine compound, comprising the following steps:

[0055] Compound 1 (tertiary ene amide) and compound 2 (organophosphorus reagent) are added to an organic solvent, followed by a promoter (manganese acetate dihydrate), and heated for reaction to obtain a meta-phosphonylated polysubstituted 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 an alkyl group, an alkoxy group or an aryl group; 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, 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 an aryl group, 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, 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, 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, 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, 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), more preferably acetic acid (AcOH).

[0071] Preferably, the 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 the time is 5-6 h.

[0072] The third technical solution of the present invention: an application of the above-mentioned meta-phosphonylated polysubstituted 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 polysubstituted pyridine compound (compound of formula IIIaa):

[0076] To a 10 mL reaction tube under air was added 0.2 mmol of the compound of Formula Ia, 0.4 mmol of the compound of Formula IIa (diphenylphosphine oxide), 0.6 mmol of Mn(OAc)3·2H2O (3.0 equiv), and 2.0 mL of acetic acid. The tube was then sealed and heated to 110°C in an oil bath for approximately 5 h. After completion, the reaction was cooled to room temperature and quenched by the addition of 20 mL of saturated aqueous NaHCO3. The mixture was extracted with ethyl acetate (3 x 30 mL). The combined organic phases were back-extracted with saturated brine, dried over anhydrous Na2SO4, and concentrated. The residue was purified by silica gel column chromatography (petroleum ether:ethyl acetate = 2:1) to afford the meta-phosphonylated polysubstituted pyridine compound (Formula IIIaa) in a 95% yield.

[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] Examples 2 to 11

[0086] 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 was replaced by an equal molar amount of the compound of formula Ib, to obtain meta-phosphonylated polysubstituted pyridine compounds (compounds of formula IIIba) 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 with a melting point of 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 was replaced by an equal molar amount of the compound of formula Ic, to obtain meta-phosphonylated polysubstituted pyridine compounds (compounds of formula IIIca) 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] Example 14

[0110] The same as Example 1, except that the compound of formula Ia was replaced by an equal molar amount of the compound of formula Id, to obtain meta-phosphonylated polysubstituted pyridine compounds (compounds of formula IIIda) 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] Example 15

[0119] The same as Example 1, except that the compound of formula Ia was replaced by an equimolar amount of the compound of formula Ie, to obtain meta-phosphonylated polysubstituted pyridine compounds (compounds of formula IIIea) 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 was replaced by an equimolar amount of the compound of formula If, to obtain meta-phosphonylated polysubstituted pyridine compounds (compounds of formula IIIfa) 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] Example 17

[0137] The same as Example 1, except that the compound of formula Ia was replaced by an equal molar amount of the compound of formula Ig, to obtain meta-phosphonylated polysubstituted pyridine compounds (compounds of formula IIIga) 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] Example 18

[0146] The same as Example 1, except that the compound of formula Ia was replaced by an equimolar amount of the compound of formula Ih, to obtain meta-phosphonylated polysubstituted pyridine compounds (compounds of formula IIIha) 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] Example 19

[0155] The same as Example 1, except that the compound of formula Ia was replaced by an equal molar amount of the compound of formula Ii, to obtain meta-phosphonylated polysubstituted pyridine compounds (compounds of formula IIIia) 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] Example 20

[0164] The same as Example 1, except that the compound of formula Ia was replaced by an equimolar amount of the compound of formula Ij, to obtain meta-phosphonylated polysubstituted pyridine compounds (compounds of formula IIIja) 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] Example 21

[0173] The same as Example 1, except that the compound of formula Ia was replaced by an equimolar amount of the compound of formula Ik, to obtain meta-phosphonylated polysubstituted pyridine compounds (compounds of formula IIIka) 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 NOP432.1512; Found 432.1502.

[0181] Example 22

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

[0183] The chemical reaction equation is as follows:

[0184]

[0185] The characterization data of the compound of formula IIIa 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] Example 23

[0191] The same as Example 1, except that the compound of formula Ia is replaced by an equal mole of the compound of formula Im, to obtain a meta-phosphonylated polysubstituted pyridine compound (compound of formula IIIma) 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] Example 24

[0200] The same as Example 1, except that the compound of formula Ia was replaced by an equimolar amount of the compound of formula In, to obtain a meta-phosphonylated polysubstituted pyridine compound (a compound of formula IIIna) 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] Example 25

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

[0210] The chemical reaction equation is as follows:

[0211]

[0212] The characterization data of the compound of formula IIIoa 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] Example 26

[0218] The same as Example 1, except that the compound of formula Ia was replaced by an equal molar amount of the compound of formula Ip, to obtain meta-phosphonylated polysubstituted pyridine compounds (compounds of formula IIIpa) 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] Example 27

[0227] The same as Example 1, except that the compound of formula Ia was replaced by an equimolar amount of the compound of formula Iq, to ​​obtain a meta-phosphonylated polysubstituted pyridine compound (compound of formula IIIqa) 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] Example 28

[0236] The same as Example 1, except that the compound of formula Ia was replaced by an equal molar 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] Example 29

[0245] The same as Example 1, except that the compound of formula Ia was replaced by an equimolar amount of the compound of formula Is, to obtain a meta-phosphonylated polysubstituted pyridine compound (compound of formula IIIsa) 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] Example 30

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

[0255] The chemical reaction equation is as follows:

[0256]

[0257] The characterization data of the compound of formula IIIta 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] Example 31

[0264] The same as Example 1, except that the compound of formula Ia was replaced by an equimolar amount of the compound of formula Iu, to obtain meta-phosphonylated polysubstituted pyridine compounds (compounds of formula IIIua) 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] Example 32

[0273] The same as Example 1, except that the compound of formula Ia was replaced by an equimolar amount of the compound of formula Iv, to obtain meta-phosphonylated polysubstituted pyridine compounds (compounds of formula IIIva) 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] Example 33

[0282] The same as Example 1, except that the compound of formula Ia was replaced by an equimolar amount of the compound of formula Iw, to obtain a meta-phosphonylated polysubstituted pyridine compound (compound of formula IIIwa) 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] Example 34

[0291] The same as Example 1, except that the compound of formula Ia was replaced by an equimolar amount of the compound of formula Ix, to obtain a meta-phosphonylated polysubstituted pyridine compound (compound of formula IIIxa) 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] Example 35

[0300] The same as Example 1, except that the compound of formula Ia was replaced by an equimolar amount of the compound of formula Iy, to obtain meta-phosphonylated polysubstituted pyridine compounds (compounds of formula IIIya) 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] Example 36

[0309] The same as Example 1, except that the compound of formula IIa (diphenylphosphine oxide) was replaced by an equimolar amount of the compound of formula IIb, to obtain meta-phosphonylated polysubstituted pyridine compounds (compounds 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] Example 37

[0318] The same as Example 1, except that the compound of formula IIa (diphenylphosphine oxide) was replaced by an equimolar amount of the compound of formula IIc, to obtain meta-phosphonylated polysubstituted pyridine compounds (compounds 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 NOP474.1981; Found 474.1974.

[0326] Example 38

[0327] The same as Example 1, except that the compound of formula IIa (diphenylphosphine oxide) was 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] Example 39

[0336] The same as Example 1, except that the compound of formula IIa (diphenylphosphine oxide) was replaced by an equimolar amount of the compound of formula IIe, to obtain an m-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] Example 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 NOP474.1981; Found 474.1992.

[0353] Example 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 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] Example 42

[0363] The same as Example 1, except that the compound of formula IIa (diphenylphosphine oxide) was 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 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] Example 43

[0372] The same as Example 1, except that the compound of formula IIa (diphenylphosphine oxide) was replaced by an equimolar amount of the compound of formula IIi, to obtain meta-phosphonylated polysubstituted pyridine compounds (compounds 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 using the following method:

[0382] (1) Insect source type: beet armyworm 3rd instar larvae;

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

[0384] (3) Test method: gastric poison potency determination, unlimited feeding method;

[0385] (4) Control agents: pyrimidinphos and triazophos;

[0386] (5) The meta-phosphonylated polysubstituted pyridine compounds prepared in the examples and the control agents (pyrimidinphos and 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. Third-instar beet armyworm larvae were starved for 5 hours. Twenty healthy third-instar beet armyworm larvae were selected for each test group. An appropriate amount of feed was evenly distributed between each insect tray. A 20 mg / L test agent solution was then injected into each tray using a micropipette. Each agent was tested in duplicate. The 20 selected insects were evenly distributed between each tray, one per tray. The trays were covered with sterilized toilet paper and sprayed with distilled water to keep them moist. A blank control was also performed. The trays were placed in a 25°C light incubator to keep them moist. Mortality of the beet armyworm larvae was counted at 24, 48, and 72 hours. Immobility or failure to crawl normally was considered mortality. The number of dead insects was recorded, and the mortality 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 shown in Table 2, some newly prepared meta-phosphonylated polysubstituted pyridine compounds exhibited moderate insecticidal activity against Spodoptera exigua larvae at a concentration of 20 mg / L. Compounds with the structures of formulae IIIba, IIIia, IIIna, IIIta, IIIwa, IIIxa, IIIab, IIIad, IIIah, and IIIai demonstrated a 72-hour mortality rate against third-instar S. exigua larvae approaching that of the control agents pirimiphos and triazophos. The results also demonstrated a positive correlation between the mortality of the compounds provided herein against third-instar S. exigua larvae and the duration of application.

[0392] The embodiments described above are merely descriptions of preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Without departing from the spirit of the present invention, various modifications and improvements made to the technical solutions of the present invention by persons skilled in the art should fall within the scope of protection defined by the claims of the present invention.

Claims

1. A meta-phosphonylated polysubstituted pyridine compound, characterized in that: The structural formula is shown in formula (1): Formula (1) Among them, 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; The R 2 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, specifically a methyl group or an ethyl group; the R 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, specifically a methyl group or an ethyl group; the 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 or 1-naphthyl; The R 5 When it is an alkoxy group, 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, 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.

2. A method for preparing the meta-phosphonylated polysubstituted pyridine compound according to claim 1, characterized in that: The following steps are involved: Adding compound 1 and compound 2 to an organic solvent, then adding a promoter, and heating to react 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 an alkyl group, an alkoxy group or an aryl group; 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 are all alkoxy or aryl; The R 2 、R 3 、R 4 、R 5 and R 6 As shown in claim 1; The R 1 When it is an alkyl group, 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 phenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 4-methylphenyl, 4-methoxyphenyl, 4-chlorophenyl, 4-fluorophenyl or 4-nitrophenyl; The accelerator is manganese acetate.

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

4. The preparation method according to claim 2, characterized in that The heating reaction temperature is 40-140°C and the time is 5-20 hours.

5. Use of the meta-phosphonylated polysubstituted pyridine compound according to claim 1 as an agent for preventing agricultural pests.

6. The application according to claim 5, characterized in that The agricultural pest is Spodoptera exigua.

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