A method for preparing meta-sulfonated polysubstituted pyridine compounds

Abstract

This invention discloses a method for preparing meta-sulfonated polysubstituted pyridine compounds, belonging to the field of organic synthesis technology. The method includes the following steps: adding an enamide of formula I and a sulfonating agent of formula II to an organic solvent, while simultaneously adding a catalyst and an oxidizing agent to promote the reaction; after the reaction, separation and purification are performed to obtain the meta-sulfonated polysubstituted pyridine compound of formula III; wherein, R... 1 Selected from alkyl, alkoxy, and aryl groups; R 2 Selected from aryl; R 3 Selected from hydrogen atoms, alkyl groups; R 4 Selected from aryl; R 5 The compounds are selected from alkyl and aryl groups. This invention features a simple reaction process that does not require multiple catalysts. Through a free radical tandem cyclization reaction, meta-sulfonated polysubstituted pyridine compounds can be obtained in one step with high efficiency, achieving a yield as high as 92%. The prepared compounds can be used as novel insecticides for controlling agricultural pests, exhibiting good efficacy and relatively low cost.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, and particularly relates to a method for preparing meta-sulfonated polysubstituted pyridine compounds. Background Technology

[0002] Sulfonated pyridines are an important class of heterocyclic compounds containing sulfonyl groups, found in numerous natural products and bioactive molecules, exhibiting a wide range of biological activities. They can also serve as basic raw materials for various transformations, leading to applications in functional materials. Therefore, the synthesis of sulfonated pyridines has attracted widespread attention from synthetic chemists, resulting in the development of numerous synthetic methods over the past few decades. However, due to the inherent electronic properties of pyridine, most existing synthetic methods can only prepare ortho- or para-sulfonated pyridines, with relatively little research on the synthesis of meta-sulfonated pyridines. Nevertheless, these meta-sulfonated pyridines play a crucial role in medicinal chemistry and agrochemicals. For example, Alvelestat is a novel neutrophil elastase inhibitor, Omidenepag is a drug for treating open-angle glaucoma and ocular hypertension, and Oxazosulfy is a broad-spectrum insecticide with a novel mechanism of action. Therefore, scientists have been continuously developing simple and efficient methods for preparing meta-sulfonated pyridines. Currently, there are two main methods for synthesizing meta-sulfonated pyridine compounds:

[0003] I. Coupling reaction of meta-preactivated pyridine with sulfonating reagent (Adv. Synth. Catal. 2019, 361, 1154-1159; Adv. Synth. Catal. 2019, 361, 956-960; ACS Catal. 2019, 9, 10668-10673; Org. Lett. 2013, 15, 6226-6229.).

[0004]

[0005] II. Dearomatization strategy, in which unsubstituted pyridine is temporarily converted into a dihydropyridine intermediate in the reaction system, then reacted with an electrophile or nucleophile, and finally re-aromatized to generate the target product (Angew. Chem. Int. Ed. 2024, 63, e202409561; Nat. Comm. 2024, 15, 7428-7435.).

[0006]

[0007] While the two methods described above can synthesize some meta-phosphonylated pyridine compounds, they still have certain drawbacks: Method one requires expensive transition metal catalysts and ligands, and it suffers from poor functional group compatibility, making it unsuitable for the preparation of polysubstituted pyridines; Method two has fewer reagents capable of dearomatizing pyridines, and the dihydropyridine intermediate is unstable. Therefore, developing simple and efficient synthetic strategies that use inexpensive and readily available chemical reagents under mild reaction conditions to prepare meta-sulfonylated pyridine compounds shows great promise. Summary of the Invention

[0008] To address the aforementioned technical problems, this invention proposes a method for preparing meta-sulfonated polysubstituted pyridine compounds. To achieve the above objective, this invention provides the following technical solution:

[0009] A method for preparing a meta-sulfonated polysubstituted pyridine compound includes the following steps: adding an enamide of formula I and a sulfonating agent of formula II to an organic solvent, while adding a catalyst and an oxidant to promote the reaction; after the reaction is completed, separation and purification are performed to obtain the meta-sulfonated polysubstituted pyridine compound of formula III.

[0010]

[0011] Among them, R 1 Selected from alkyl, alkoxy, or aryl; R 2 Selected from aryl; R 3 Selected from hydrogen atoms or alkyl groups; R 4 Selected from aryl; R 5 Selected from alkyl or aryl groups.

[0012] This invention uses tertiary amides and sulfonyl hydrazides as basic raw materials to prepare meta-sulfonated pyridine compounds with different substitutions in one step via an intramolecular free radical tandem cyclization-aromatization reaction. The reaction raw materials of this invention are inexpensive and readily available, have high atom economy, broad substrate versatility, and are highly operable.

[0013] Furthermore, the molar ratio of the enamide, sulfonating agent, catalyst, and oxidant is 1:(1-2):(0.1-0.4):(2-4). Optimization experiments have demonstrated that the reaction proceeds smoothly within this molar ratio range, with the only difference being the yield. The highest yield is achieved at a ratio of 1:1.5:0.2:3, therefore, 1:1.5:0.2:3 is preferred.

[0014] Further, the organic solvent is selected from any one of acetonitrile, toluene, N,N-dimethylformamide, tetrahydrofuran, tert-butanol, and dichloromethane. The concentration of the organic solvent is 0.1 mol / L.

[0015] Furthermore, the catalyst is copper bromide.

[0016] Furthermore, the oxidant is dicumyl peroxide.

[0017] Furthermore, the reaction temperature is 40-120℃, and the reaction time is 8-30 hours. Through optimization experiments, this invention has found that the reaction can occur within this temperature range, but the reaction yield varies depending on the reaction time. The highest yield is achieved at 90-100℃ for 10-12 hours. Therefore, the preferred reaction temperature is 90-100℃, and the preferred reaction time is 10-12 hours.

[0018] Furthermore, the R 1 When it is an alkyl group, the alkyl group is selected from methyl, ethyl, and isopropyl; R 1 When it is an alkoxy group, the alkoxy group is either tert-butoxy or benzyloxy; R 1 When it is aryl, the aryl group is selected from phenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 4-methylphenyl, 4-methoxyphenyl, 4-chlorophenyl or 4-fluorophenyl;

[0019] The R 2 When it is aryl, the aryl group is selected from phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 3-bromophenyl, 2-bromophenyl, 4-methylphenyl, 3-methylphenyl, 2-methylphenyl, 4-methoxyphenyl or 2-naphthyl;

[0020] The R 3 When it is an alkyl group, the alkyl group is methyl or ethyl;

[0021] The R 4 When it is aryl, the aryl group is selected from phenyl, 4-methoxyphenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 4-chlorophenyl, 4-cyanophenyl, 4-trifluoromethylphenyl, 4-phenylphenyl, 1-naphthyl or thienyl;

[0022] The R 5 When it is aryl, the aryl group is selected from phenyl, 4-methoxyphenyl, 4-methylphenyl, 4-chlorophenyl, 4-bromophenyl, 4-nitrophenyl, or thiophene; R 5 When selected from alkyl groups, the alkyl group is ethyl, butyl, or cyclopropyl.

[0023] The meta-sulfonated polysubstituted pyridine compounds prepared using the above method can be used to prevent agricultural pests.

[0024] Compared with the prior art, the present invention has the following advantages and technical effects:

[0025] 1. The reaction process of this invention is simple and does not require multiple catalysts. Through a free radical tandem cyclization reaction, meta-sulfonated polysubstituted pyridine compounds can be obtained in one step with high efficiency and yield up to 92%.

[0026] 2. The reaction of the present invention does not require the participation of highly toxic reagents and avoids expensive precious metal catalysts. The target product can be synthesized using conventional reaction reagents, solvents and catalysts.

[0027] 3. The sulfonating reagent used in the method of the present invention does not need to be prepared and can be directly purchased commercially, thus avoiding cumbersome reaction steps and improving the atom economy of the reaction.

[0028] 4. The reaction conditions involved in this invention are relatively suitable, do not require high-pressure reaction, do not require a strict anhydrous and oxygen-free environment, the operation is very simple, the product yield is high, and the active groups can be further derivatized.

[0029] 5. The compounds provided by this invention can be used as new insecticides to control agricultural pests, with good effects and relatively low cost. Detailed Implementation

[0030] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0031] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Every smaller range between any stated value or intermediate value within a stated range, and any other stated value or intermediate value within said range, is also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0032] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0033] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be readily apparent to those skilled in the art. This specification and embodiments are merely exemplary.

[0034] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.

[0035] This invention provides a novel method for preparing meta-sulfonated polysubstituted pyridine compounds, comprising the following steps: adding an enamide of formula I and a sulfonating agent of formula II to an organic solvent, while simultaneously adding a catalyst and an oxidizing agent to promote the reaction; after the reaction is completed, separation and purification are performed to obtain the meta-sulfonated polysubstituted pyridine compound of formula III; the reaction is as follows:

[0036]

[0037] Among them, R 1 Selected from alkyl, alkoxy, or aryl; R 2 Selected from aryl; R 3 Selected from hydrogen atoms or alkyl groups; R 4 Selected from aryl; R 5 Selected from alkyl or aryl groups.

[0038] In some feasible embodiments, the molar ratio of the enamide, sulfonating agent, catalyst, and oxidant is 1:(1-2):(0.1-0.4):(2-4). As a typical but non-limiting example, in the following preferred embodiments of the invention, the molar ratio of the enamide, sulfonating agent, catalyst, and oxidant may be selected as 1:1.5:0.2:3.

[0039] In some feasible embodiments, the organic solvent is selected from any one of acetonitrile, toluene, N,N-dimethylformamide, tetrahydrofuran, tert-butanol, and dichloromethane. As a typical but non-limiting example, in the following preferred embodiments of the invention, the organic solvent may be dichloromethane. The concentration of the organic solvent is 0.1 mol / L.

[0040] In some feasible embodiments, the catalyst is copper bromide.

[0041] In some feasible embodiments, the oxidant is dicumyl peroxide.

[0042] In some feasible embodiments, the reaction temperature is 40-120°C and the reaction time is 8-30 hours. A preferred reaction temperature is 90-100°C and the reaction time is 10-12 hours. As a typical but non-limiting example, in the following preferred embodiments of the invention, the reaction temperature may be 90°C and the reaction time may be 12 hours.

[0043] In some feasible embodiments, the R 1 When it is an alkyl group, the alkyl group is methyl, ethyl, or isopropyl; R 1 When it is an alkoxy group, the alkoxy group is either tert-butoxy or benzyloxy; R 1 When it is aryl, the aryl group is phenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 4-methylphenyl, 4-methoxyphenyl, 4-chlorophenyl, or 4-fluorophenyl.

[0044] In some feasible embodiments, the R 2 When it is aryl, the aryl group is phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 3-bromophenyl, 2-bromophenyl, 4-methylphenyl, 3-methylphenyl, 2-methylphenyl, 4-methoxyphenyl, or 2-naphthyl.

[0045] In some feasible embodiments, the R 3 When it is an alkyl group, the alkyl group is methyl or ethyl.

[0046] In some feasible embodiments, the R 4 When it is aryl, the aryl group is phenyl, 4-methoxyphenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 4-chlorophenyl, 4-cyanophenyl, 4-trifluoromethylphenyl, 4-phenylphenyl, 1-naphthyl or thienyl.

[0047] In some feasible embodiments, the R 5 When it is aryl, the aryl group is phenyl, 4-methoxyphenyl, 4-methylphenyl, 4-chlorophenyl, 4-bromophenyl, 4-nitrophenyl, or thiophene; R 5 When it is an alkyl group, the alkyl group is ethyl, butyl, or cyclopropyl.

[0048] For example, the specific operation steps of the new method provided by the present invention are as follows: In an air atmosphere, the enamide (0.2 mmol, 1.0 equiv) shown in Formula I and the sulfonyl hydrazine reagent (0.3 mmol, 1.5 equiv) shown in Formula II are added to an organic solvent. Under the action of a catalyst (0.04 mmol, 0.2 equiv) and an oxidant (0.6 mmol, 3.0 equiv), the reaction is carried out at a reaction temperature of T degrees Celsius for 12 hours. After the reaction is completed, separation and purification are performed to obtain the meta-sulfonated polysubstituted pyridine compound shown in Formula III.

[0049] Unless otherwise specified, "room temperature" in this invention refers to 20-30℃.

[0050] All raw materials used in this invention were purchased commercially. The sulfonyl hydrazine reagent was purchased from Shanghai Maclean Biochemical Technology Co., Ltd.; the enamide was prepared in-house, and the preparation method is referenced in J.Org.Chem.2022,87,3014-3024; the catalyst and oxidant were purchased from Shanghai Maclean Biochemical Technology Co., Ltd.

[0051] The technical solution of the present invention will be further illustrated by the following embodiments.

[0052] Example 1

[0053] The reaction formula for preparing the compound represented by the IIIaa structural formula is as follows:

[0054]

[0055] Under air atmosphere, compound Ia (0.2 mmol, 1.0 equiv), benzenesulfonyl hydrazine (0.3 mmol, 1.5 equiv), CuBr2 (0.04 mmol, 0.2 equiv), dicumyl peroxide (0.6 mmol, 3.0 equiv, DCP), and 2.0 mL of 0.1 mol / L dichloromethane (DCM) were added to a 10 mL reaction tube. The reaction tube was then sealed and heated to 90 °C in an oil bath for 12 h. After the reaction was complete, the mixture was cooled to room temperature and purified directly by silica gel column chromatography (petroleum ether:ethyl acetate volume ratio = 4:1) to obtain the compound represented by the structure IIIaa, in 85% yield.

[0056] The characterization data of the obtained compounds are as follows:

[0057] The compound is a white solid with a melting point (mp): 158-160℃.

[0058] 1 H NMR(500MHz,Chloroform-d)δ9.50(s,1H),7.56-7.52(m,2H),7.50-7.42(m,4H) ,7.37-7.33(m,1H),7.32-7.21(m,6H),6.81(dd,J=8.0,1.3Hz,2H),1.90(s,3H);

[0059] 13C NMR(126MHz,Chloroform-d)δ164.0,150.6,146.3,140.7,139.8,134.45,134.4 2,133.0,131.7,129.2,129.1,129.0,128.8,128.5,128.3,128.2,128.0,18.1;

[0060] HRMS(ESI)m / z[M+H] + Calcd.for C 24 H 20 NO2S 386.1209; Found 386.1216.

[0061] Example 2-12

[0062] The reaction formula for preparing the compound represented by the IIIaa structural formula is as follows:

[0063]

[0064] Except for compound Ia, which differs from Example 1, the types and amounts of other reaction reagents, reaction conditions, and operations are the same as in Example 1. The structures of specific compounds of formula Ia are shown in Table 1.

[0065] Table 1

[0066]

[0067]

[0068]

[0069] Example 13

[0070] The reaction formula for preparing the compound represented by the IIIba structural formula is as follows:

[0071]

[0072] The preparation method was the same as in Example 1, and the compound of formula IIIba was obtained with a yield of 87%.

[0073] The characterization data of the obtained compounds are as follows:

[0074] The compound is a white solid with a melting point (mp): 164-166℃.

[0075] 1H NMR(500MHz,Chloroform-d)δ9.48(s,1H),7.49-7.41(m,3H),7.36-7.32(m,1H),7.30-7.21(m,8H),6.79(d,J=7.3Hz,2H),2.41(s,3H),1.90(s,3H);

[0076] 13 C NMR(126MHz,Chloroform-d)δ164.1,150.5,146.3,140.8,139.0,137.0,134.6,134 .2,133.0,131.6,129.20,129.16,129.1,128.7,128.25,128.15,128.0,21.5,18.2;

[0077] HRMS(ESI)m / z[M+H] + Calcd.for C 25 H 22 NO2S 400.1366; Found 400.1375.

[0078] Example 14

[0079] The reaction formula for preparing the compound represented by the IIIca structural formula is as follows:

[0080]

[0081] The preparation method was the same as in Example 1, and the compound of formula IIIca was prepared with a yield of 61%.

[0082] The characterization data of the obtained compounds are as follows:

[0083] The compound is a white solid with a melting point (mp): 168-170℃.

[0084] 1 H NMR(500MHz,Chloroform-d)δ9.48(s,1H),7.55-7.50(m,2H),7.49-7.44(m,1H),7.35(t,J=7.6 Hz,1H),7.31-7.22(m,6H),7.04-6.97(m,2H),6.80(d,J=7.2Hz,2H),3.87(s,3H),1.92(s,3H);

[0085] 13C NMR(126MHz,Chloroform-d)δ163.6,160.3,150.6,146.3,140.8,134.6,133.9,133 .0,132.2,131.4,130.8,129.2,128.7,128.25,128.16,1278.0,113.9,55.5,18.3;

[0086] HRMS(ESI)m / z[M+H] + Calcd.for C 25 H 22 NO3S 416.1315; Found 416.1307.

[0087] Example 15

[0088] The reaction formula for preparing the compound represented by the IIIda structural formula is as follows:

[0089]

[0090] The preparation method was the same as in Example 1, and the compound of formula IIIda was obtained with a yield of 80%.

[0091] The characterization data of the obtained compounds are as follows:

[0092] The compound is a white solid with a melting point (mp): 164-165℃.

[0093] 1 H NMR(500MHz,Chloroform-d)δ9.49(s,1H),7.56-7.52(m,2H),7.51-7.45(m,1H),7.3 8-7.33(m,1H),7.31-7.22(m,6H),7.21-7.14(m,2H),6.82-6.77(m,2H),1.89(s,3H);

[0094] 13 C NMR(126MHz,Chloroform-d)δ163.2(d,J C-F =249.5Hz),162.9,150.8,146.4,140.7,135.8,134.6,134.3,133.1,131.7,131.2(d,J C-F =8.8Hz),129.1,128.8,128.4,128.2,128.0,115.6(d,J C-F =21.4Hz), 18.1;

[0095] HRMS(ESI)m / z[M+H] + Calcd.for C 24 H 19 FNO2S 404.1115;Found 404.1108.

[0096] Example 16

[0097] The reaction formula for preparing the compound represented by the structural formula IIIea is as follows:

[0098]

[0099] The preparation method was the same as in Example 1, and the compound of formula IIIea was prepared with a yield of 75%.

[0100] The characterization data of the obtained compounds are as follows:

[0101] The compound is a white solid with a melting point (mp): 169-170℃.

[0102] 1 H NMR(500MHz,Chloroform-d)δ9.49(s,1H),7.51-7.43(m,5H),7.37-7.33(m,1H),7.31-7.21(m,6H),6.82-6.76(m,2H),1.89(s,3H);

[0103] 13 C NMR(126MHz,Chloroform-d)δ162.8,150.8,146.5,140.6,138.2,135.2,134.7, 134.3,133.1,131.7,130.6,129.1,128.79,128.76,128.4,128.2,128.0,18.1;

[0104] HRMS(ESI)m / z[M+H] + Calcd.for C 24 H 19 ClNO2S 420.0820; Found 420.0826.

[0105] Example 17

[0106] The reaction formula for preparing the compound represented by the IIIfa structural formula is as follows:

[0107]

[0108] The preparation method was the same as in Example 1, and the compound of formula IIIfa was obtained with a yield of 70%.

[0109] The characterization data of the obtained compounds are as follows:

[0110] The compound is a white solid with a melting point (mp): 189-191℃.

[0111] 1 H NMR(500MHz,Chloroform-d)δ9.49(s,1H),7.62(d,J=8.4Hz,2H),7.48(dq,J=8.6,4.0Hz,1H),7 .45-7.40(m,2H),7.35(t,J=7.5Hz,1H),7.30-7.22(m,6H),6.79(d,J=7.0Hz,2H),1.89(s,3H);

[0112] 13 C NMR(126MHz,Chloroform-d)δ162.8,150.8,146.5,140.6,138.7,134.7,134.2 ,133.1,131.7,131.6,130.9,129.1,128.8,128.4,128.2,128.0,123.5,18.1;

[0113] HRMS(ESI)m / z[M+H] + Calcd.for C 24 H 19 BrNO2S 464.0314,466.0294; Found464.0321,466.0301.

[0114] Example 18

[0115] The reaction formula for preparing the compound represented by the IIIga structural formula is as follows:

[0116]

[0117] The preparation method was the same as in Example 1, and the compound shown in Formula IIIga was prepared with a yield of 72%.

[0118] The characterization data of the obtained compounds are as follows:

[0119] The compound is a white solid with a melting point (mp): 173-175℃.

[0120] 1H NMR (500MHz, Chloroform-d) δ9.49 (s, 1H), 7.67 (d, J = 8.0Hz, 1H), 7.50-7.46 (m, 1H), 7.44 (t, J = 7. 4Hz,1H),7.37-7.31(m,3H),7.31-7.28(m,4H),7.27-7.22(m,2H),6.84-6.78(m,2H),1.72(s,3H);

[0121] 13 C NMR(126MHz,Chloroform-d)δ163.6,150.2,146.4,140.7,135.3,134.1,133.1,133.0, 130.3,130.0,129.3,129.1,128.8,128.4,128.2,128.13,128.06,127.9,122.1,17.0;

[0122] HRMS(ESI)m / z[M+H] + Calcd.for C 24 H 19 BrNO2S 464.0314,466.0294; Found464.0320,466.0300.

[0123] Example 19

[0124] The reaction formula for preparing the compound represented by the IIIha structural formula is as follows:

[0125]

[0126] The preparation method was the same as in Example 1, and the compound of formula IIIha was obtained with a yield of 75%.

[0127] The characterization data of the obtained compounds are as follows:

[0128] The compound is a white solid with a melting point (mp): 172-174℃.

[0129] 1 H NMR(500MHz,Chloroform-d)δ9.49(s,1H),7.69(d,J=1.8Hz,1H),7.58(d,J=7.9Hz,1H),7. 50-7.44(m,2H),7.38-7.33(m,2H),7.29-7.22(m,6H),6.79(d,J=7.5Hz,2H),1.89(s,3H);

[0130] 13C NMR(126MHz,Chloroform-d)δ162.4,150.8,146.4,141.7,140.6,135.0,134.2,133.1 ,132.2,132.1,131.8,130.0,129.1,128.8,128.4,128.2,128.0,127.7,122.6,18.0;

[0131] HRMS(ESI)m / z[M+H] + Calcd.for C 24 H 19 BrNO2S 464.0314,466.0294; Found464.0324,466.0303.

[0132] Example 20

[0133] The reaction formula for preparing the compound represented by the structural formula IIIia is as follows:

[0134]

[0135] The preparation method was the same as in Example 1, and the compound of formula IIIia was obtained with a yield of 90%.

[0136] The characterization data of the obtained compounds are as follows:

[0137] The compound is a white solid with a melting point (mp): 173-174℃.

[0138] 1 H NMR(500MHz,Chloroform-d)δ9.55(s,1H),8.03(s,1H),7.94(d,J=8.4Hz,1H),7.91-7.87(m,2H),7.68-7.63(m,1H),7 .56-7.50(m,2H),7.47(t,J=7.0Hz,1H),7.35(t,J=7.5Hz,1H),7.32-7.22(m,6H),6.83(d,J=7.5Hz,2H),1.95(s,3H);

[0139] 13C NMR(126MHz,Chloroform-d)δ163.9,150.7,146.4,140.8,137.2,137.1,134.5,134.4,133.4,133.1, 131.9,129.2,128.9,128.8,128.6,128.3,128.22,128.19,128.0,127.9,127.0,126.7,126.6,18.2;

[0140] HRMS(ESI)m / z[M+H] + Calcd.for C 28 H 22 NO2S 436.1366;Found 436.1375.

[0141] Example 21

[0142] The reaction formula for preparing the compound represented by the IIIja structural formula is as follows:

[0143]

[0144] The preparation method was the same as in Example 1, and the compound of formula IIIja was obtained with a yield of 92%.

[0145] The characterization data of the obtained compounds are as follows:

[0146] The compound is a white solid with a melting point (mp): 162-164℃.

[0147] 1 H NMR(500MHz,Chloroform-d)δ9.52(s,1H),7.55-7.50(m,3H),7.50-7.42(m,3H),7.32 -7.27(m,5H),7.11(t,J=7.6Hz,2H),6.70(d,J=7.5Hz,1H),1.85(s,3H),1.57(s,3H);

[0148] 13 C NMR(126MHz,Chloroform-d)δ164.0,150.4,146.8,140.4,139.7,136.2,134.3,133.9,13 3.3,131.6,130.1,129.4,129.1,129.0,128.9,128.8,128.51,128.47,125.8,19.4,17.3;

[0149] HRMS(ESI)m / z[M+H] +Calcd.for C 25 H 22 NO2S 400.1366;Found 400.1359.

[0150] Example 22

[0151] The reaction formula for preparing the compound represented by the IIIka structural formula is as follows:

[0152]

[0153] The preparation method was the same as in Example 1, and the compound shown in Formula IIIka was obtained with a yield of 90%.

[0154] The characterization data of the obtained compounds are as follows:

[0155] The compound is a white solid with a melting point (mp): 151-153℃.

[0156] 1 H NMR(500MHz,Chloroform-d)δ9.50(s,1H),7.55-7.51(m,2H),7.50-7.41(m,4H),7.32-7.27(m,4H),7.1 9(t,J=7.5Hz,1H),7.14(d,J=7.6Hz,1H),6.74(d,J=7.5Hz,1H),6.41(s,1H),2.19(s,3H),1.90(s,3H);

[0157] 13 C NMR(126MHz,Chloroform-d)δ164.0,150.7,146.3,140.8,139.9,137.7,134.5,134.4,13 2.9,131.6,129.4,129.1,129.0,128.9,128.6,128.5,128.14,128.05,126.5,21.5,18.0;

[0158] HRMS(ESI)m / z[M+H] + Calcd.for C 25 H 22 NO2S 400.1366; Found 400.1358.

[0159] Example 23

[0160] The reaction formula for preparing the compound represented by the IIIla structural formula is as follows:

[0161]

[0162] The preparation method was the same as in Example 1, and the compound of formula IIIa was obtained with a yield of 80%.

[0163] The characterization data of the obtained compounds are as follows:

[0164] The compound is a white solid with a melting point (mp): 142-144℃.

[0165] 1 H NMR(500MHz,Chloroform-d)δ9.51(s,1H),7.54(d,J=7.3Hz,2H),7.51-7.42(m,4H),7.35-7.27(m,4H),7 .20(t,J=7.5Hz,1H),7.15(d,J=7.6Hz,1H),6.74(d,J=7.4Hz,1H),6.41(s,1H),2.19(s,3H),1.91(s,3H);

[0166] 13 C NMR(126MHz,Chloroform-d)δ163.7,151.1,146.1,140.7,139.5,137.7,134.7,134. 3,133.0,131.9,129.4,129.2,129.1,128.6,128.5,128.2,128.1,126.4,21.5,18.1;

[0167] HRMS(ESI)m / z[M+H] + Calcd.for C 25 H 22 NO2S 400.1366; Found 400.1360.

[0168] Example 24

[0169] The reaction formula for preparing the compound represented by the IIIma structural formula is as follows:

[0170]

[0171] The preparation method was the same as in Example 1, and the compound of formula IIIma was obtained with a yield of 76%.

[0172] The characterization data of the obtained compounds are as follows:

[0173] The compound is a white solid with a melting point (mp): 170-172℃.

[0174] 1H NMR(500MHz,Chloroform-d)δ9.48(s,1H),7.56-7.50(m,2H),7.50-7.42(m,4H),7. 35-7.27(m,4H),6.81-6.75(m,2H),6.72(d,J=8.3Hz,2H),3.86(s,3H),1.91(s,3H);

[0175] 13 C NMR(126MHz,Chloroform-d)δ164.0,159.6,150.5,146.3,140.8,140.0,134.9,1 33.0,132.2,130.5,129.1,128.9,128.7,128.5,127.9,126.5,113.6,55.4,18.1;

[0176] HRMS(ESI)m / z[M+H] + Calcd.for C 25 H 22 NO3S 416.1315; Found 416.1308.

[0177] Example 25

[0178] The reaction formula for preparing the compound represented by the IIIna structural formula is as follows:

[0179]

[0180] The preparation method was the same as in Example 1, and the compound of formula IIIna was obtained with a yield of 75%.

[0181] The characterization data of the obtained compounds are as follows:

[0182] The compound is a white solid with a melting point (mp): 190-191℃.

[0183] 1 H NMR(500MHz,Chloroform-d)δ9.49(s,1H),7.55-7.43(m,6H),7.38-7.32(m,4H),7.25-7.20(m,2H),6.79-6.72(m,2H),1.91(s,3H);

[0184] 13C NMR(126MHz,Chloroform-d)δ164.2,149.3,146.3,140.6,139.5,134.7,134.6 ,133.3,132.8,131.6,130.6,129.2,129.1,128.9,128.6,128.5,127.9,18.1;

[0185] HRMS(ESI)m / z[M+H] + Calcd.for C 24 H 19 ClNO2S 420.0820; Found 420.0813.

[0186] Example 26

[0187] The reaction formula for preparing the compound represented by the structural formula IIIoa is as follows:

[0188]

[0189] The preparation method was the same as in Example 1, and the compound of formula IIIoa was prepared with a yield of 78%.

[0190] The characterization data of the obtained compounds are as follows:

[0191] The compound is a white solid with a melting point (mp): 229-230℃.

[0192] 1 H NMR (500MHz, Chloroform-d) δ9.47 (s, 1H), 7.58-7.45 (m, 8H), 7.38-7.31 (m, 4H), 6.97 (d, J = 8.1Hz, 2H), 1.89 (s, 3H);

[0193] 13 C NMR(126MHz,Chloroform-d)δ164.6,148.1,146.6,140.6,139.40,139.37,133. 9,133.6,131.9,130.8,130.2,129.3,129.1,128.6,127.8,118.4,112.5,18.1;

[0194] HRMS(ESI)m / z[M+H] + Calcd.for C 25 H 19 N2O2S 411.1162; Found 411.1157.

[0195] Example 27

[0196] The reaction formula for preparing the compound represented by the IIIpa structural formula is as follows:

[0197]

[0198] The preparation method was the same as in Example 1, and the compound of formula IIIpa was obtained with a yield of 70%.

[0199] The characterization data of the obtained compounds are as follows:

[0200] The compound is a white solid with a melting point (mp): 186-187℃.

[0201] 1 H NMR (500MHz, Chloroform-d) δ9.51 (s, 1H), 7.56-7.45 (m, 8H), 7.33-7.27 (m, 4H), 6.96 (d, J = 7.9Hz, 2H), 1.91 (s, 3H);

[0202] 13 C NMR (126MHz, DMSO-d6) δ169.7,146.5,141.0,140.8,138.9,135.3,133.7,130.7,129.9,129.4,128.7(q,J C-F =31.5Hz),128.3,128.2,127.8,127.6,126.5,126.1,124.6(q,J C-F =3.8Hz), 124.2(q,J C-F =273.4Hz), 120.5, 15.7;

[0203] HRMS(ESI)m / z[M+H] + Calcd.for C 25 H 19 F3NO2S 454.1083; Found 454.1090.

[0204] Example 28

[0205] The reaction formula for preparing the compound represented by structural formula IIIqa is as follows:

[0206]

[0207] The preparation method was the same as in Example 1, and the compound shown in Formula IIIqa was obtained with a yield of 78%.

[0208] The characterization data of the obtained compounds are as follows:

[0209] The compound is a white solid with a melting point (mp): 176-178℃.

[0210] 1 H NMR(500MHz,DMSO-d6)δ9.35(s,1H),7.72(d,J=7.3Hz,2H),7.65-7.59(m,3H),7.55-7.47(m,7H),7 .41(t,J=7.4Hz,1H),7.37(t,J=7.8Hz,2H),7.34-7.30(m,2H),6.90(d,J=8.1Hz,2H),1.90(s,3H);

[0211] 13 C NMR (126MHz, DMSO-d6) δ163.3,149.5,145.4,140.0,139.9,139.6,139.4,134.0,133.5,13 3.0,131.5,129.5,129.1,129.04,128.99,128.8,128.2,127.8,127.3,126.8,126.1,17.8;

[0212] HRMS(ESI)m / z[M+H] + Calcd.for C 30 H 24 NO2S 462.1522;Found 462.1528.

[0213] Example 29

[0214] The reaction formula for preparing the compound represented by the IIIra structural formula is as follows:

[0215]

[0216] The preparation method was the same as in Example 1, and the compound of formula IIIra was prepared with a yield of 86%.

[0217] The characterization data of the obtained compounds are as follows:

[0218] The compound is a white solid with a melting point (mp): 194-196℃.

[0219] 1H NMR(500MHz,Chloroform-d)δ9.63(s,1H),7.90(d,J=8.2Hz,1H),7.77(d,J=8.2Hz,1H),7.60-7.52(m,3H),7.5 1-7.42(m,3H),7.35-7.27(m,2H),7.10-7.00(m,4H),6.87(t,J=7.6Hz,2H),6.65(d,J=8.3Hz,1H),1.79(s,3H);

[0220] 13 C NMR(126MHz,Chloroform-d)δ163.8,149.0,146.7,139.7,139.5,135.5,133.1,132.7,132.6,131.5 ,130.5,129.4,129.2,129.1,128.6,128.5,128.4,128.2,127.8,126.7,125.9,125.2,124.1,17.4;

[0221] HRMS(ESI)m / z[M+H] + Calcd.for C 28 H 22 NO2S 436.1366;Found 436.1372.

[0222] Example 30

[0223] The reaction formula for preparing the compound represented by the IIIsa structural formula is as follows:

[0224]

[0225] The preparation method was the same as in Example 1, and the compound of formula IIIsa was obtained with a yield of 80%.

[0226] The characterization data of the obtained compounds are as follows:

[0227] The compound is a white solid with a melting point (mp): 180-181℃.

[0228] 1H NMR(500MHz,Chloroform-d)δ9.51(s,1H),7.53(dd,J=8.1,1.7Hz,2H),7.51-7.44(m,4H),7.44-7.41(m,2H),7.38( dd,J=5.1,1.2Hz,1H),7.34(t,J=7.8Hz,2H),7.03(dd,J=5.1,3.5Hz,1H),6.80(dd,J=3.5,1.2Hz,1H),2.03(s,3H);

[0229] 13 C NMR (126MHz, Chloroform-d) δ164.1,146.5,143.8,140.5,139.6,136.0,133.8,133.6,133.2,130.3,129.1,128.9,128.5,128.4,127.9,126.9,18.2;

[0230] HRMS(ESI)m / z[M+H] + Calcd.for C 22 H 18 NO2S2392.0773;Found 392.0780.

[0231] Example 31

[0232] The reaction formula for preparing the compound represented by the IIIta structural formula is as follows:

[0233]

[0234] The preparation method was the same as in Example 1, and the compound of formula IIIta was prepared in 50% yield.

[0235] The characterization data of the obtained compounds are as follows:

[0236] The compound is a white solid with a melting point (mp): 135-137℃.

[0237] 1 H NMR(500MHz,Chloroform-d)δ9.57(s,1H),8.06(td,J=5.8,5.1,3.2Hz,2H),7.57(s,1H),7.53- 7.36(m,5H),7.45-7.37(m,2H),7.29(q,J=7.7Hz,4H),7.23(t,J=7.8Hz,2H),7.08-7.03(m,2H);

[0238] 13C NMR (126MHz, Chloroform-d) δ161.2,151.1,149.7,140.6,137.4,136.2,134.2,133.1,130.7,129.4,129.1,128.8,128.7,128.0,127.9,127.7,123.2;

[0239] HRMS(ESI)m / z[M+H] + Calcd.for C 23 H 18 NO2S 372.1053; Found 372.1045.

[0240] Example 32

[0241] The reaction formula for preparing the compound represented by the IIIua structural formula is as follows:

[0242]

[0243] The preparation method was the same as in Example 1, and the compound shown in Formula IIIua was prepared with a yield of 74%.

[0244] The characterization data of the obtained compounds are as follows:

[0245] The compound is a white solid with a melting point (mp): 161-163℃.

[0246] 1 H NMR(500MHz,Chloroform-d)δ9.48(s,1H),7.50-7.42(m,6H),7.36-7.31(m,1H),7.30-7.26( m,4H),7.21(t,J=7.6Hz,2H),6.86-6.80(m,2H),2.33(q,J=7.4Hz,2H),0.63(t,J=7.4Hz,3H);

[0247] 13 C NMR(126MHz,Chloroform-d)δ164.7,149.9,146.3,140.7,140.2,137.8,134.9,13 3.6,133.0,129.7,128.8,128.7,128.49,128.47,128.2,127.9,127.7,22.7,14.7;

[0248] HRMS(ESI)m / z[M+H] + Calcd.for C 25 H 22NO2S 400.1366;Found 400.1373.

[0249] Example 33

[0250] The reaction formula for preparing the compound represented by the IIIab structural formula is as follows:

[0251]

[0252] The preparation method was the same as in Example 1, and the compound of formula IIIab was obtained with a yield of 78%.

[0253] The characterization data of the obtained compounds are as follows:

[0254] The compound is a white solid with a melting point (mp): 183-185℃.

[0255] 1 H NMR(500MHz,Chloroform-d)δ9.47(s,1H),7.55-7.50(m,2H),7.49-7.42(m,3H),7.39-7.33(m,1H),7.26(t, J=7.61Hz,2H),7.17(d,J=8.1Hz,2H),7.07(d,J=8.0Hz,2H),6.83(d,J=7.1Hz,2H),2.37(s,3H),1.89(s,3H);

[0256] 13 C NMR(126MHz,Chloroform-d)δ163.9,150.5,146.3,144.0,139.9,137.9,134.7,13 4.6,131.6,129.4,129.2,129.1,128.9,128.5,128.3,128.10,128.07,21.7,18.1;

[0257] HRMS(ESI)m / z[M+H] + Calcd.for C 25 H 22 NO2S 400.1366; Found 400.1375.

[0258] Example 34

[0259] The reaction formula for preparing the compound represented by the IIIac structural formula is as follows:

[0260]

[0261] The preparation method was the same as in Example 1, and the compound of formula IIIac was prepared with a yield of 80%.

[0262] The characterization data of the obtained compounds are as follows:

[0263] The compound is a white solid with a melting point (mp): 180-181℃.

[0264] 1 H NMR(400MHz,Chloroform-d)δ9.46(s,1H),7.55-7.50(m,2H),7.50-7.42(m,3H),7.39-7.34(m,1H),7 .32-7.27(m,2H),7.23-7.17(m,2H),6.90-6.82(m,2H),6.78-6.69(m,2H),3.83(s,3H),1.89(s,3H);

[0265] 13 C NMR(101MHz,Chloroform-d)δ163.8,163.4,150.3,146.3,140.0,135.0,134.8,1 32.5,131.5,130.3,129.3,129.1,128.9,128.5,128.3,128.2,114.0,55.8,18.1;

[0266] HRMS(ESI)m / z[M+H] + Calcd.for C 25 H 22 NO3S 416.1315; Found 416.1322.

[0267] Example 35

[0268] The reaction formula for preparing the compound represented by the IIIad structural formula is as follows:

[0269]

[0270] The preparation method was the same as in Example 1, and the compound of formula IIIad was obtained with a yield of 68%.

[0271] The characterization data of the obtained compounds are as follows:

[0272] The compound is a white solid with a melting point (mp): 187-189℃.

[0273] 1H NMR(400MHz,Chloroform-d)δ9.52(s,1H),8.13-8.05(m,2H),7.56-7.52(m,2H),7.51-7.45(m,4 H),7.44(d,J=2.0Hz,1H),7.43-7.37(m,1H),7.30-7.23(m,2H),6.86-6.78(m,2H),1.92(s,3H);

[0274] 13 C NMR(101MHz,Chloroform-d)δ165.0,150.4,150.2,146.5,146.4,139.6,134.2 ,133.4,131.9,129.4,129.3,129.2,129.1,128.8,128.6,128.4,123.8,18.1;

[0275] HRMS(ESI)m / z[M+H] + Calcd.for C 24 H 19 N2O4S 431.1060; Found 431.1068.

[0276] Example 36

[0277] The reaction formula for preparing the compound represented by the IIIae structural formula is as follows:

[0278]

[0279] The preparation method was the same as in Example 1, and the compound of formula IIIae was obtained with a yield of 72%.

[0280] The characterization data of the obtained compounds are as follows:

[0281] The compound is a white solid with a melting point (mp): 196-198℃.

[0282] 1 H NMR(500MHz,Chloroform-d)δ9.48(s,1H),7.55-7.51(m,2H),7.50-7.42(m,3H),7.41-7.36(m,1H),7 .29(t,J=7.6Hz,2H),7.24(d,J=8.7Hz,2H),7.19(d,J=8.7Hz,2H),6.84(d,J=7.1Hz,2H),1.91(s,3H);

[0283] 13C NMR (126MHz, Chloroform-d) δ164.3,150.4,146.3,139.81,139.76,139.2,134.4,134.2,131.8,129.5,129.3,129.1,129.0,128.5,128.3,18.1;

[0284] HRMS(ESI)m / z[M+H] + Calcd.for C 24 H 19 ClNO2S 420.0820; Found 420.0811.

[0285] Example 37

[0286] The reaction formula for preparing the compound represented by the IIIaf structural formula is as follows:

[0287]

[0288] The preparation method was the same as in Example 1, and the compound of formula IIIaf was obtained with a yield of 75%.

[0289] The characterization data of the obtained compounds are as follows:

[0290] The compound is a white solid with a melting point (mp): 179-181℃.

[0291] 1 H NMR(400MHz,Chloroform-d)δ9.48(s,1H),7.55-7.51(m,2H),7.51-7.44(m,3H),7.43-7. 36(m,3H),7.29(dd,J=8.3,7.0Hz,2H),7.16-7.08(m,2H),6.87-6.80(m,2H),1.90(s,3H);

[0292] 13 C NMR(101MHz,Chloroform-d)δ164.4,150.4,146.4,139.9,139.8,134.4,134 .1,132.0,131.7,129.5,129.3,129.10,129.07,128.5,128.4,128.3,18.1;

[0293] HRMS(ESI)m / z[M+H] + Calcd.for C 24 H 19BrNO2S 464.0314,466.0294; Found464.0307,466.0287.

[0294] Example 38

[0295] The reaction formula for preparing the compound represented by the IIIag structural formula is as follows:

[0296]

[0297] The preparation method was the same as in Example 1, and the compound shown in formula IIIag was prepared with a yield of 70%.

[0298] The characterization data of the obtained compounds are as follows:

[0299] The compound is a white solid with a melting point (mp): 164-166℃.

[0300] 1 H NMR(500MHz,Chloroform-d)δ9.42(s,1H),7.57-7.51(m,3H),7.50-7.42(m,3H),7.41-7.36(m,1H),7.3 6-7.30(m,2H),6.99-6.93(m,2H),6.90(dd,J=3.8,1.4Hz,1H),6.85(dd,J=5.0,3.8Hz,1H),1.93(s,3H);

[0301] 13 C NMR(126MHz,Chloroform-d)δ164.1,150.4,146.0,141.9,139.8,135.1,134 .6,134.2,131.7,129.1,129.00,128.98,128.5,128.4,128.2,127.3,18.1;

[0302] HRMS(ESI)m / z[M+H] + Calcd.for C 22 H 18 NO2S2392.0773;Found 392.0765.

[0303] Example 39

[0304] The reaction formula for preparing the compound represented by the IIIah structural formula is as follows:

[0305]

[0306] The preparation method was the same as in Example 1, and the compound of formula IIIah was prepared with a yield of 65%.

[0307] The characterization data of the obtained compounds are as follows:

[0308] The compound is a white solid with a melting point (mp): 151-153℃.

[0309] 1 H NMR(400MHz,Chloroform-d)δ9.24(s,1H),7.57-7.53(m,2H),7.53-7.42(m,6H) ),7.33-7.28(m,2H),2.69(q,J=7.4Hz,2H),2.02(s,3H),1.16(t,J=7.4Hz,3H);

[0310] 13 C NMR (101MHz, Chloroform-d) δ164.2,150.3,147.4,139.8,135.0,131.7,131.5,129.1,129.0,128.7,128.5,49.9,18.3,7.3;

[0311] HRMS(ESI)m / z[M+H] + Calcd.for C 20 H 20 NO2S 338.1209; Found 338.1217.

[0312] Application Example 1

[0313] Testing of the insecticidal bioactivity of the compounds of formula III prepared in Examples 1 and 13-39 against diamondback moth larvae.

[0314] (1) Determination method: Weigh 4 mg of the newly prepared compound and dissolve it in 4 mL of a mixed solvent of methanol and acetone (volume ratio 1:1) to prepare a 1000 mg / L solution. Take 1 mL of the solution and dilute it 50 times to prepare a 20 mg / L solution for later use. Dilute the remaining 3 mL of the solution 20 times to prepare a 50 mg / L solution for later use. Set up a control group (Oxazosulfyl, purchased from Shanghai Yifei Biotechnology Co., Ltd.) in the same way, and use distilled water with added methanol and acetone as a blank control experimental group. In addition, prepare round cabbage leaves with a diameter of 4 cm. Use an airbrush sprayer to evenly spray the two solutions of different mass concentrations onto different cabbage leaves. Then place the cabbage leaves in a petri dish lined with filter paper and let them air dry naturally. Then add 10 third instar larvae of diamondback moth to each cabbage leaf and raise them in an incubator for 48 h. Record the number of live and dead diamondback moths at 24 h and 48 h respectively.

[0315] (2) Activity representation: The insecticidal activity of the compound is characterized by the corrected mortality rate. The higher the mortality rate, the higher the insecticidal activity of the compound.

[0316] Mortality rate / % = Number of dead insects / Number of tested insects × 100

[0317] Corrected mortality rate / % = (treatment mortality rate - control mortality rate) / (1 - control mortality rate) × 100

[0318] (3) The experimental results are shown in Table 2.

[0319] Table 2. Insecticidal activity test results of the target compounds

[0320]

[0321]

[0322] Analysis of the data in Table 2 shows that some of the newly prepared compounds represented by Formula III exhibited certain insecticidal activity against diamondback moth larvae at concentrations of 20 mg / L and 50 mg / L. Among them, compounds represented by Formulas IIIda, IIIoa, IIIpa, IIIsa, IIIad, and IIIah showed higher mortality rates against third-instar diamondback moth larvae, with IIIpa and IIIah exhibiting the best insecticidal activity, similar to that of Oxazosulfyl. The results also indicate that the mortality rate of the compounds provided in this invention against third-instar diamondback moth larvae is positively correlated with the duration of application.

[0323] The above are merely preferred embodiments of this application, but the scope of protection of this application is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the scope of the technology disclosed in this application should be included within the scope of protection of this application. Therefore, the scope of protection of this application should be determined by the scope of the claims.

Claims

1. A method for preparing meta-sulfonated polysubstituted pyridine compounds, characterized in that, Includes the following steps: The enamide shown in Formula I and the sulfonating agent shown in Formula II were added to an organic solvent, and a catalyst and an oxidant were added to promote the reaction. After the reaction was completed, the mixture was separated and purified to obtain the meta-sulfonated polysubstituted pyridine compound shown in Formula III. Among them, R 1 Selected from alkyl, alkoxy, or aryl; R 2 Selected from aryl; R 3 Selected from hydrogen atoms or alkyl groups; R 4 Selected from aryl; R 5 Selected from alkyl or aryl groups; The catalyst is copper bromide; The R 1 When it is an alkyl group, the alkyl group is selected from methyl, ethyl, or isopropyl; R 1 When it is an alkoxy group, the alkoxy group is selected from tert-butoxy or benzyloxy; R 1 When it is aryl, the aryl group is selected from phenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 4-methylphenyl, 4-methoxyphenyl, 4-chlorophenyl or 4-fluorophenyl; The R 2 When it is aryl, the aryl group is selected from phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 3-bromophenyl, 2-bromophenyl, 4-methylphenyl, 3-methylphenyl, 2-methylphenyl, 4-methoxyphenyl or 2-naphthyl; The R 3 When it is an alkyl group, the alkyl group is methyl or ethyl; The R 4 When it is aryl, the aryl group is selected from phenyl, 4-methoxyphenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 4-chlorophenyl, 4-cyanophenyl, 4-trifluoromethylphenyl, 4-phenylphenyl, 1-naphthyl or thienyl; The R 5 When it is aryl, the aryl group is selected from phenyl, 4-methoxyphenyl, 4-methylphenyl, 4-chlorophenyl, 4-bromophenyl, 4-nitrophenyl, or thiophene; R 5 When it is an alkyl group, the alkyl group is ethyl, butyl, or cyclopropyl.

2. The method for preparing meta-sulfonated polysubstituted pyridine compounds according to claim 1, characterized in that, The molar ratio of the amide, sulfonating agent, catalyst and oxidant is 1:(1-2):(0.1-0.4):(2-4).

3. The method for preparing meta-sulfonated polysubstituted pyridine compounds according to claim 2, characterized in that, The molar ratio of the amide, sulfonating agent, catalyst, and oxidant is 1:1.5:0.2:

3.

4. The method for preparing meta-sulfonated polysubstituted pyridine compounds according to claim 1, characterized in that, The organic solvent is selected from any one of acetonitrile, toluene, N,N-dimethylformamide, tetrahydrofuran, tert-butanol, and dichloromethane.

5. The method for preparing meta-sulfonated polysubstituted pyridine compounds according to claim 1, characterized in that, The oxidant is dicumyl peroxide.

6. The method for preparing meta-sulfonated polysubstituted pyridine compounds according to claim 1, characterized in that, The reaction temperature is 40-120℃, and the reaction time is 8-30 hours.

7. The method for preparing meta-sulfonated polysubstituted pyridine compounds according to claim 6, characterized in that, The reaction temperature is 90-100℃, and the reaction time is 10-12 hours.

Images