CN103130766B - Piperine hydrazone or acylhydrazone or sulfonyl hydrazone derivative substances and application for preparing a botanical insecticide - Google Patents

Abstract

The invention relates to a series of piperine hydrazone/acylhydrazone/sulfonyl hydrazone derivatives and their application in the preparation of botanical pesticides. The series of piperine hydrazone/acylhydrazone/sulfonyl hydrazone derivatives use piperine as raw material Piperine aldehyde is obtained by hydrolysis, esterification, reduction and oxidation, and then reacted with substituted phenylhydrazine, hydrazide, and sulfonylhydrazide respectively, and its general structure is shown below. The applicant's experiments show that the series of piperine hydrazone/acylhydrazone/sulfonyl hydrazone derivatives have good antifeedant and poisonous activity against third-instar armyworms, some of which are higher than the parent piperine, and some of the compounds are insecticidal The activity is higher than that of the commercialized botanical pesticides toosendanin, so it is expected to be used in the preparation of highly efficient, environmentally friendly, and low-toxic botanical pesticides.

Description

Piperine hydrazone/acylhydrazone/sulfonylhydrazone derivatives and their application in the preparation of botanical pesticides

technical field

The invention relates to a series of piperine hydrazone/acylhydrazone/sulfonyl hydrazone compounds with insecticidal activity, in particular to piperine hydrazone/acylhydrazone/sulfonyl hydrazone derivatives and their application for preparing plant-derived insecticides.

Background technique

Piperine is an amide derivative alkaloid in the piperaceae (Piperaceae) plant of the genus Piper. focus of research.

In the existing literature, some studies have been done on the inhibition of enzyme activity, anti-oxidation, anti-tumor, and insecticide of piperine and its derivatives: for example:

Literature [Li-Hua Mu, Bo Wang, Hao-Yang Ren, et al.Synthesis and inhibitory effect of piperine derives on monoamine oxidase. Bioorganic & Medicinal Chemistry Letters.2012, 22, 3343-3348.] reported piperine and its synthetic amide, Ester derivatives have the effect of selectively inhibiting monoamine oxidase (MAO) A and B in vitro and literature [Surrinder Koul, Jawahir L.Koul, Subhash C.Taneja, et al.Structure-Activity Relationship of Piperine and its Synthetic Analogues for their Inhibitory Potentials of Rat Hepatic Microsomal Constitutive and Inducible Cytochrome P450 Activities. Bioorganic & Medicinal Chemistry. 2000, 8, 251-268.] reported that piperine and its amides derivatives can inhibit cytochrome P450 activity in vitro and in vivo. Literature [Badmaev V, Majeed M, Prakash L.Piperine derived from black pepper increases the plasma levels of coenzymeq10following oral supplementation.J.ofNutritional Biochemistry.2000,11(2):109-113.] found that piperine can significantly reduce The activity of glutathione dismutase (SOD), peroxidase (CAT), glutathione peroxidase (GPX) and glutathione group transferase (GSP) can reduce the activity of liver, kidney, heart, intestine, etc. The concentration of glutathione in the body proves that piperine can reduce the cellular peroxidation induced by high-fat food. Literature [S.K.Reshmi, E.Sathya andP.Suganya Devi.Isolation of piperdine from Piper nigrum and its antiproliferative activity.African Journal of Pharmacy and Pharmacology.2010, 4 (8), 562-573.] reported its antiproliferative activity. Literature [Sunila E S, Kuttan G. Immunomodulatory and antitumor activity of Piperlongum Linn and piperine. J. of Ethnopharmacology. 2004, 90 (2-3): 339-346.] The study found that piperine significantly inhibited the establishment of DLA cells in mice. Tumor growth, and prolong the survival rate of EAC tumor mice from 37.3% to 58.8% [Selvendiran K, Prince Vijeya Singh J, Sakthis ekaran D.Invivo effect of piperine on serum and tissue glycoprotein levels in benzo(a) pyrene inducedlung carcinogenesis in Swiss salbino mice. Pulm Pharmacol Ther. 2006, 19 (2): 107-111.] The study found that piperine can inhibit benzene-induced lung cancer. [Zheng Bin, Wang Xin, Ma Tonghui. In vitro experimental study on the antitumor activity of piperine on human liver cancer HepG2 cells. Chinese Experimental Diagnostics, 2012, 16 (2), 218-220.] To explore the effect of piperine on The effect on the proliferation, killing and apoptosis of human HepG2 liver cancer cell line provides a theoretical basis for the treatment of liver cancer. Literature [Inder Pal Singh, Shreyans Kumar Jain, Amandeep Kaur, et al.Synthesis and Antileishmanial activity of Piperoyl-Amino Acid Conjugates.European Journal of Medicinal Chemistry.2010, 45, 3439-3445.] reported that the derivatives of piperine have a The epimastigotes and amastigotes of Mannia had better activity. In the article, the in vivo activity of the two compounds with the best activity was studied using the golden hamster as the model animal for Lehmania donovani. Literature [Tatiana Santana Ribeiro, Leonardo Freire-de-Lima, Jos Osvaldo Previato, et al. Toxic effects of natural piperine and its derivatives on epimastigotes and amastigotes of Trypanosoma cruzi. Bioorganic & Medicinal Chemistry 0 Letters. The effect of the natural product piperine and its amine derivatives on Trypanosoma cruzi is expected to find a new drug that can kill trypanosomiasis and cure the human disease called Chagas caused by trypanosomiasis. The literature [Vanderlu cia F de Paula, Luiz C de A Barbosa, Antonio J Demuner, et al. Synthesis and insecticidal activity of new amide derivatives of piperine. Pest Manag Sci. 2000, 56, 168-174.] studied piperine amide The poisonous effect of derivatives on Ascia monuste orseis Latr, Acanthoscelides obtectus Say, Brevicoryne brassicae L, Protopolybia exigua DeSaus and Cornitermes cumulans Kollar. Literature [Wang Jia. Study on the Cytotoxic Effect of Piperine on Culex pipiens larvae and Spodoptera frugiperda [D]. Suzhou: Soochow University, 2006.] reported the effect of piperine on Culex pipiens larvae and Sf-21 cells Strong toxicity and growth inhibition, can be used as functional substances of new insecticides. In view of this, at present, piperine and its derivatives, in addition to the research on enzyme activity inhibition, anti-oxidation, anti-tumor, etc., are also used in the protozoa Trypanosoma cruzi and Lehmania donovani, the insect Culex palustris larvae and Spodoptera frugiperda. There are certain studies on the poisonous activity of piperine and its derivatives, but the activity of piperine and its derivatives in antifeedant and poisonous killing of armyworms has not been reported, so the piperine hydrazones/acylhydrazones/sulfonyl hydrazone derivatives The synthesis and research on its antifeedant and poisonous activity of armyworm are very novel.

Contents of the invention

The purpose of the present invention is to provide a series of piperine hydrazone/acylhydrazone/sulfonylhydrazone derivatives, and provide the preparation method of these derivatives.

To achieve the above tasks, the present invention is achieved through the following technical solutions:

Piperine hydrazone/acylhydrazone/sulfonyl hydrazone derivatives are characterized in that their general chemical formula is:

In the formula, R are respectively:

The preparation method of the above-mentioned piperine hydrazone/acylhydrazone/sulfonyl hydrazone derivatives is characterized in that piperine is used as raw material to obtain piperine aldehyde through hydrolysis, esterification, reduction and oxidation, and then respectively combined with substituted phenylhydrazine, acylhydrazone Hydrazine, and sulfonylhydrazide reaction, obtain series of piperine hydrazone/acylhydrazone/sulfonylhydrazone derivatives, specifically prepared according to the following steps:

Dissolve a certain amount of piperine aldehyde and the corresponding substituted phenylhydrazine/hydrazide with absolute ethanol, then add two drops of glacial acetic acid dropwise to the above solution, heat to reflux, TLC tracking detection, after the reaction is completed, suction filter and use Wash with ice absolute ethanol and petroleum ether in turn to obtain the desired pure product.

The substituted phenylhydrazines, hydrazides and sulfonylhydrazines used are respectively:

a. Phenylhydrazines: o-nitrophenylhydrazine, p-nitrophenylhydrazine, 2, 3, 5, 6-tetrafluorophenylhydrazine;

b. Hydrazides: acetyl hydrazide, cyanoacetyl hydrazide, benzoyl hydrazide, p-toluyl hydrazide, m-toluyl hydrazide, o-toluyl hydrazide, p-hydroxybenzoic hydrazide, p-nitrobenzoyl hydrazide Hydrazine, m-nitrobenzohydrazide, p-methoxybenzohydrazide, m-methoxybenzohydrazide, 3,4-dimethoxybenzohydrazide, o-ethoxybenzohydrazide, p-fluorobenzoic hydrazide, m-fluorobenzoic hydrazide, m-chlorobenzoic hydrazide, o-chlorobenzoic hydrazide, 2, 4, 6-trichlorobenzoic hydrazide, niacin, isoniazid, 2- Thiophene hydrazide, 5-chloro-2-thienyl hydrazide, 5-bromo-2-thienyl hydrazide;

c. Sulfonylhydrazides: benzenesulfonylhydrazide, p-toluenesulfonylhydrazide, p-ethylbenzenesulfonylhydrazide, p-methoxybenzenesulfonylhydrazide, p-bromobenzenesulfonylhydrazide, m-nitrobenzenesulfonylhydrazide, p-Chloro-m-nitrobenzenesulfonyl hydrazide.

According to the test of the applicant, the piperine hydrazone/acylhydrazone/sulfonylhydrazone derivatives have high efficiency and low toxicity insecticidal activity, and can be used to prepare plant-derived insecticides.

Description of drawings

Figure 1 and Figure 2 are the hydrogen spectrum and carbon spectrum of compound 6, respectively.

The present invention is described in further detail below through the accompanying drawings and the embodiments given by the inventor.

Detailed ways

The applicant has synthesized a series of new piperine hydrazone/acylhydrazone/sulfonylhydrazine derivatives, whose general chemical formula is:

In the formula, R are respectively:

The preparation method of the above-mentioned piperine hydrazone/acylhydrazone/sulfonylhydrazone derivatives uses piperine as a raw material to obtain piperine aldehyde through hydrolysis, esterification, reduction and oxidation, and then respectively reacts with substituted phenylhydrazine, hydrazide and sulfonylhydrazone Hydrazide reaction to get.

The substituted phenylhydrazines, hydrazides and sulfonylhydrazines used are respectively:

a. Phenylhydrazines: o-nitrophenylhydrazine, p-nitrophenylhydrazine, 2, 3, 5, 6-tetrafluorophenylhydrazine;

b. Hydrazides: acetyl hydrazide, cyanoacetyl hydrazide, benzoyl hydrazide, p-toluyl hydrazide, m-toluyl hydrazide, o-toluyl hydrazide, p-hydroxybenzoic hydrazide, p-nitrobenzoyl hydrazide Hydrazine, m-nitrobenzohydrazide, p-methoxybenzohydrazide, m-methoxybenzohydrazide, 3,4-dimethoxybenzohydrazide, o-ethoxybenzohydrazide, p-fluorobenzoic hydrazide, m-fluorobenzoic hydrazide, m-chlorobenzoic hydrazide, o-chlorobenzoic hydrazide, 2, 4, 6-trichlorobenzoic hydrazide, niacin, isoniazid, 2- Thiophene hydrazide, 5-chloro-2-thienyl hydrazide, 5-bromo-2-thienyl hydrazide;

c. Sulfonylhydrazides: benzenesulfonylhydrazide, p-toluenesulfonylhydrazide, p-ethylbenzenesulfonylhydrazide, p-methoxybenzenesulfonylhydrazide, p-bromobenzenesulfonylhydrazide, m-nitrobenzenesulfonylhydrazide, p-Chloro-m-nitrobenzenesulfonyl hydrazide.

The applicant has conducted research on the insecticidal activity of the above-mentioned piperine hydrazone/acylhydrazone/sulfonyl hydrazone derivatives. The results show that the piperine hydrazone/acylhydrazone/sulfonylhydrazide derivatives have strong antifeedant and poisonous activities against third-instar armyworms, and can be used to prepare high-efficiency and low-toxicity botanical insecticides.

The following are examples given by the inventors.

Example 1:

1. Products: piperine acid, piperine ester, piperine alcohol, piperine aldehyde and compound 1-33 (see the following content for details on the physical and chemical properties of each compound)

2. Preparation method:

The following is the synthetic route of piperine acid:

Dissolve a certain amount of potassium hydroxide in 95% ethanol, then add piperine to the above reaction solution, reflux in an oil bath for a certain period of time, cool and filter at room temperature to obtain a solid, dissolve it in a certain amount of water, and adjust the pH with hydrochloric acid The value is acidic, suction filtered, the filter cake is washed with a small amount of water and dried to obtain the desired pure product.

Physical and chemical properties of piperine acid:

1), yellow solid, melting point 218°C.

2) Mass spectrometry (ESI-MS) characteristics of piperine acid:

Electrospray ionization: m/z: 241.00 ([M+Na] ⁺ , 100).

3) NMR spectrum characteristics of piperine acid:

With deuterated dimethyl sulfoxide as the solvent and TMS as the internal standard, the peaks are assigned as follows: ¹ H NMR (400MHz, DMSO-d ₆ ) δ: 12.22 (s, 1H, -COOH), 7.27-7.33 (m, 1H), 7.23-7.24 (m, 1H), 6.92-7.02 (m, 4H), 6.06 (s, 2H, -OCH ₂ O-), 5.91-5.95 (m, 1H);

Following is the synthetic route of piperine ester:

Dissolve a certain amount of piperine acid in methanol, add a few drops of concentrated sulfuric acid to the above reaction solution, stir and reflux in an oil bath for a certain period of time, remove the solvent by rotary evaporation and add a certain amount of dichloromethane to dissolve, and concentrate The desired pure product was obtained by column separation.

Physicochemical properties of piperine ester:

1) Light yellow solid, melting point 146°C.

2), the mass spectrometry (ESI-MS) characteristics of piperine ester:

Electrospray ionization: m/z: 232.90 ([M+H] ⁺ , 85), 254.90 ([M+Na] ⁺ , 87).

3) The nuclear magnetic resonance spectrum ( ¹ HNMR, 400MHz) characteristics of piperine ester:

With deuterated chloroform as the solvent and TMS as the internal standard, the peaks are assigned as follows: ¹ HNMR (400MHz, CDCl ₃ ) δ: 7.38-7.44 (m, 1H), 6.98-6.99 (m, 1H), 6.90-6.92 ( m, 1H), 6.77-6.83 (m, 2H), 6.66-6.73 (m, 1H), 5.98 (s, 2H, _-OCH2O- ), 5.93-5.96 (m, 1H), 3.76 (s, 3H , -CH ₃ );

Following is the synthetic route of piperine alcohol:

Slowly add the tetrahydrofuran solution of piperine ester in an ice-water bath into the tetrahydrofuran suspension of lithium aluminum tetrahydrogen and aluminum trichloride, and then react at this temperature until the TLC plate detects that the substrate reaction is complete, and then add water to the reaction system to stop reaction. After suction filtration, the filter cake was washed with dichloromethane and methanol, and the filtrate was combined, concentrated and separated by a column to obtain the desired pure product.

The physical and chemical properties of piperine alcohol:

1) Light yellow solid, melting point 99-101°C.

2) Mass spectrometry (ESI-MS) characteristics of piperine alcohol:

Electrospray ionization: m/z: 226.90 ([M+Na] ⁺ , 68).

3) NMR characteristics of piperine alcohol:

With deuterated chloroform as the solvent and TMS as the internal standard, the peaks are assigned as follows: ¹ H NMR (500MHz, CDCl ₃ ) δ: 6.94 (s, 1H), 6.81 (d, 1H, J=8Hz), 6.74 (d , 1H, J=8.0Hz), 6.59-6.64 (m, 1H), 6.45-6.48 (m, 1H), 6.35-6.40 (m, 1H), 5.89-5.95 (m, 3H), 4.23 (d, 2H , J=5.5Hz), 1.48(s, 1H);

The following is the synthetic route of piperine aldehyde:

The piperine alcohol and manganese dioxide were dissolved in tetrahydrofuran, and the oil bath was refluxed until the TLC detection was complete. The solid was removed by suction filtration, and the filtrates were combined, concentrated and separated by a column to obtain the desired pure product.

The physical and chemical properties of piperine aldehyde:

1), yellow solid, melting point 108°C.

2) Mass spectrometry (ESI-MS) characteristics of piperine aldehyde:

Electrospray ionization: m/z: 202.90 ([M+H] ⁺ , 100).

3) NMR spectrum characteristics of piperine aldehyde:

With deuterated chloroform as the solvent and TMS as the internal standard, the peaks are assigned as follows: ¹ H NMR (500MHz, CDCl ₃ ) δ: 9.58 (d, 1H, J=8.0Hz, -CHO), 7.20-7.23 (m, 1H), 7.03 (s, 1H), 6.91-6.97 (m, 2H), 6.80-6.85 (m, 2H), 6.20-6.25 (m, 1H), 6.00 (s, 2H, -OCH2O-).

The following is the synthetic route of compound 1-33:

Dissolve a certain amount of piperine aldehyde and substituted phenylhydrazine/hydrazide/sulfonylhydrazide with absolute ethanol, then add two drops of glacial acetic acid to the above solution, heat to reflux, TLC tracking detection, after the reaction, The desired compound was obtained after suction filtration.

The physical and chemical properties of compound 1 are as follows:

1), red solid;

2), the NMR spectrum characteristics of the compound:

With deuterated dimethyl sulfoxide as the solvent and TMS as the internal standard, the peaks are assigned as follows: ¹ H NMR (500MHz, DMSO-d ₆ ) δ: 11.19 (s, 0.9H, NH), 10.78 (s, 0.1H , NH), 8.10 (d, 2H, J=8.5Hz), 7.78 (d, 1H, J=9.5Hz), 7.17-7.22 (m, 1H), 6.90-7.06 (m, 5H), 6.68-6.79 ( m, 2H), 6.46-6.51 (m, 1H), 6.04 (s, 2H, -OCH ₂ O-); ¹³ CNMR (125MHz, DMSO-d ₆ ) δ: 151.51, 150.61, 148.41, 147.84, 144.97, 142.08 .

The physicochemical properties of compound 2 are as follows:

1), red solid, melting point 166-168°C;

2), the NMR spectrum characteristics of the compound:

With deuterated dimethyl sulfoxide as the solvent and TMS as the internal standard, the peaks are assigned as follows: ¹ H NMR (500MHz, DMSO-d ₆ ) δ: 11.08 (s, 1H, NH), 8.21 (d, 1H, J =9.5Hz), 8.08 (d, 1H, J=8.5Hz), 7.78 (d, 1H, J=8.5Hz), 7.60 (t, 1H, J=7.5Hz), 7.20 (s, 1H), 6.87- 7.04 (m, 4H), 6.73-6.78 (m, 2H), 6.49-6.54 (m, 1H), 6.04 (s, 2H, -OCH ₂ O-); ¹³ C NMR (125MHz, DMSO-d6) δ: 148.41, 148.15, 147.94, 141.43, 139.19, 136.78, 135.56, 131.69, 131.02, 128.88, 127.36, 126.16, 122.72, 118.59, 116.29, 108.98, 105.84, 101.71.

3) High-resolution mass spectrometry characteristics of the compound:

Ionization by electrospray: Calcd for C ₁₈ H ₁₅ N ₃ O ₄ ([M+H] ⁺ ), 338.1135; Found, 338.1140.

The physicochemical properties of compound 3 are as follows:

1), green solid, melting point 161°C;

2), the nuclear magnetic resonance spectrum ( ¹ HNMR, 500MHz) characteristics of the compound:

With deuterated dimethyl sulfoxide as the solvent and TMS as the internal standard, the peaks are assigned as follows: ¹ H NMR (500MHz, DMSO-d ₆ ) δ: 10.27 (s, 1H, NH), 7.89 (d, 1H, J =9.5Hz), 7.14-7.21(m,2H), 6.88-6.99(m,3H), 6.62-6.69(m,2H), 6.38-6.43(m,1H), 6.03(s,2H, _-OCH2 O-); ¹³ C NMR (125MHz, DMSO-d ₆ ) δ: 147.84, 147.19, 145.14, 145.02, 144.82, 137.39, 136.54, 135.33, 133.88, 131.28, 128.56, 127.02, 125.01, 121.8301, 108 , 95.28, 95.09, 94.90.

3) High-resolution mass spectrometry characteristics of the compound:

Ionization by electrospray: Calcd for C ₁₈ H ₁₂ F ₄ N ₂ O ₂ ([M+H] ⁺ ), 365.0907; Found, 365.0908.

The physicochemical properties of compound 4 are as follows:

1), pale yellow solid;

2), the NMR spectrum characteristics of the compound:

With deuterated dimethyl sulfoxide as the solvent and TMS as the internal standard, the peaks are assigned as follows: ¹ H NMR (400MHz, DMSO-d ₆ ) δ: 11.18 (s, 0.38H, NH), 11.06 (s, 0.62H , NH), 7.79 (d, 0.38H, J=9.6Hz), 7.68 (d, 0.62H, J=9.6Hz), 7.18-7.21 (m, 1H), 6.89-7.03 (m, 3H), 6.69- 6.80 (m, 2H), 6.33-6.42 (m, 1H), 6.03 (s, 2H, _-OCH2O- ), 2.09 (s, 1.86H, _-CH3 ), 1.90 (s, 1.14H, -CH ₃ ).

The physicochemical properties of compound 5 are as follows:

1), orange solid;

2), the NMR spectrum characteristics of the compound:

With deuterated dimethyl sulfoxide as the solvent and TMS as the internal standard, the peaks are assigned as follows: ¹ H NMR (500MHz, DMSO-d ₆ ) δ: 11.61 (s, 0.75H, NH), 11.53 (s, 0.25H , NH), 7.82 (d, 0.25H, J=9.5Hz), 7.70 (d, 0.75H, J=9.5Hz), 7.20-7.25 (m, 1H), 6.72-7.04 (m, 5H), 6.32- 6.43 (m, 1H), 6.04 (s, 2H, -OCH ₂ O-), 4.07 (s, 1.5H, -CH ₂ CN), 3.76 (s, 0.5H, -CH ₂ CN); ¹³ C NMR ( 125MHz，DMSO-d ₆ ）δ:164.85，159.07，150.09，148.42，148.05，147.25，141.25，140.70，136.36，136.16，131.50，128.24，128.07，127.11，122.94，122.85，116.52，116.27，108.98，105.88，101.74 , 25.26, 24.74.

The physicochemical properties of compound 6 are as follows:

1), pale yellow solid, melting point 214-216°C;

2), the NMR spectrum characteristics of the compound:

With deuterated dimethyl sulfoxide as the solvent and TMS as the internal standard, the peaks are assigned as follows: ¹ H NMR (500MHz, DMSO-d ₆ ) δ: 11.68 (s, 1H, NH), 8.14 (d, 1H, J =9.5Hz), 7.88 (d, 2H, J=7.5Hz), 7.57 (t, 1H, J=7.0Hz), 7.50 (t, 2H, J=7.0Hz), 7.23 (s, 1H), 7.01- 7.07 (m, 1H), 6.96 (d, 1H, J=8.0Hz), 6.90 (d, 1H, J=7.5Hz), 6.75-6.85 (m, 2H), 6.47-6.52 (m, 1H), 6.05 (s, 2H, -OCH ₂ O-); ¹³ C NMR (125MHz, DMSO-d6) δ: 162.75, 149.62, 147.85, 147.44, 139.85, 135.41, 133.32, 131.58, 131.02, 128.34, 127.47, 126.70, 122.26, 108.39, 105.30, 101.14.

3) High-resolution mass spectrometry characteristics of the compound:

Ionization by electrospray: Calcd for C ₁₉ H ₁₆ N ₂ O ₃ ([M+Na] ⁺ ), 343.1053; Found, 343.1054.

The physicochemical properties of compound 7 are as follows:

1), yellow solid, melting point 233-234°C;

2), the NMR spectrum characteristics of the compound:

With deuterated dimethyl sulfoxide as the solvent and TMS as the internal standard, the peaks are assigned as follows: ¹ H NMR (400MHz, DMSO-d ₆ ) δ: 11.60 (s, 1H, NH), 8.13 (d, 1H, J =9.6Hz), 7.79 (d, 2H, J=8.0Hz), 7.31 (d, 2H, J=8.0Hz), 7.23 (s, 1H), 6.96-7.07 (m, 2H), 6.90 (d, 1H , J=8.0Hz), 6.74-6.84 (m, 2H), 6.46-6.52 (m, 1H), 6.04 (s, 2H, -OCH ₂ O-), 2.37 (s, 3H, -CH ₃ ).

The physicochemical properties of compound 8 are as follows:

1), pale yellow solid, melting point 212-213°C;

2), the NMR spectrum characteristics of the compound:

With deuterated dimethyl sulfoxide as the solvent and TMS as the internal standard, the peaks are assigned as follows: ¹ H NMR (500MHz, DMSO-d ₆ ) δ: 11.61 (s, 1H, NH), 8.13 (d, 1H, J =9.5Hz), 7.67-7.70 (m, 2H), 7.39-7.41 (m, 2H), 7.22 (s, 1H), 7.01-7.06 (m, 1H), 6.96 (d, 1H, J=8.0Hz) , 6.90 (d, 1H, J=7.5Hz), 6.75-6.84 (m, 2H), 6.46-6.51 (m, 1H), 6.04 (s, 2H, -OCH ₂ O-), 2.38 (s, 3H, -CH ₃ ); ¹³ C NMR (125MHz, DMSO-d ₆ ) δ: 162.83, 149.50, 147.86, 147.44, 139.75, 137.67, 135.38, 133.32, 132.15, 131.04, 128.37, 128, 22, 127.96, 126.72, 122.23, 108.39, 105.33, 101.14, 20.83.

3) High-resolution mass spectrometry characteristics of the compound:

Ionization by electrospray: Calcd for C ₂₀ H ₁₈ N ₂ O ₃ ([M+H] ⁺ ), 335.1390; Found, 335.1385.

The physicochemical properties of compound 9 are as follows:

1), yellow solid;

2), the NMR spectrum characteristics of the compound:

With deuterated dimethyl sulfoxide as the solvent and TMS as the internal standard, the peaks are assigned as follows: ¹ H NMR (400MHz, DMSO-d ₆ ) δ: 11.58 (s, 0.2H, NH), 11.57 (s, 0.8H , NH), 7.97 (d, 0.8H, J=9.6Hz), 7.77 (d, 0.2H, J=9.6Hz), 7.21-7.41 (m, 5H), 6.87-7.12 (m, 3H), 6.67- 6.85 (m, 2H), 6.44-6.50 (m, 0.8H), 6.14-6.20 (m, 0.2H), 6.04 (s, 1.6H, -OCH2O-), 6.02 (s, _0.4H , -OCH ₂ O-), 2.35 (s, 2.4H, -CH ₃ ), 2.21 (s, 0.6H, -CH ₃ ).

The physicochemical properties of compound 10 are as follows:

1), pale yellow solid;

2), the NMR spectrum characteristics of the compound:

With deuterated dimethyl sulfoxide as the solvent and TMS as the internal standard, the peaks are assigned as follows: ¹ H NMR (500MHz, DMSO-d ₆ ) δ: 11.47 (s, 1H, NH), 10.13 (s, 1H, OH ), 8.10 (d, 1H, J=9.0Hz), 7.76 (d, 2H, J=8.0Hz), 7.22 (s, 1H), 6.73-7.05 (m, 7H), 6.45-6.50 (m, 1H) , 6.04 (s, 2H, -OCH ₂ O-); ¹³ C NMR (125MHz, DMSO-d ₆ ) δ: 162.36, 160.52, 148.68, 147.85, 147.38, 139.25, 135.09, 131.06, 129.52, 128.54, 126.77, 123.75 , 122.19, 114.87, 108.39, 105.27, 101.13.

The physical and chemical properties of compound 11 are as follows:

1), pale yellow solid;

2), the NMR spectrum characteristics of the compound:

With deuterated dimethyl sulfoxide as the solvent and TMS as the internal standard, the peaks are assigned as follows: ¹ H NMR (500MHz, DMSO-d ₆ ) δ: 11.95 (s, 0.9H, NH), 11.86 (s, 0.1H , NH), 8.35 (d, 1.8H, J=8.5Hz), 8.28 (d, 0.2H, J=8.0Hz), 8.11-8.16 (m, 2.8H), 7.90 (d, 0.2H, J=8.0 Hz), 7.23 (s, 1H), 6.77-7.08 (m, 5H), 6.47-6.52 (m, 1H), 6.05 (s, 2H, -OCH ₂ O-); ¹³ C NMR (125MHz, DMSO-d ₆ ) δ: 161.07, 150.73, 149.09, 147.86, 147.52, 140.68, 138.97, 135.86, 130.95, 129.02, 128.00, 126.62, 123.52, 122.38, 108.40, 105.32, 101.17.

3) High-resolution mass spectrometry characteristics of the compound:

Ionization by electrospray: Calcd for C ₁₉ H ₁₅ N ₃ O ₅ ([M+H] ⁺ ), 366.1084; Found, 366.1089.

The physicochemical properties of compound 12 are as follows:

1), pale yellow solid;

2), the NMR spectrum characteristics of the compound:

With deuterated dimethyl sulfoxide as the solvent and TMS as the internal standard, the peaks are assigned as follows: ¹ H NMR (400MHz, DMSO-d ₆ ) δ: 11.98 (s, 1H, NH), 8.72-8.73 (m, 1H ), 8.42-8.44 (m, 1H), 8.33 (d, 1H, J=8.0Hz), 8.16 (d, 1H, J=9.6Hz), 7.81 (t, 1H, J=8.0Hz), 7.23 (d , 1H, J=1.2Hz), 6.97-7.09 (m, 2H), 6.77-6.92 (m, 3H), 6.47-6.54 (m, 1H), 6.05 (s, 2H, -OCH ₂ O-).

The physicochemical properties of compound 13 are as follows:

1), pale yellow solid, melting point 214-216°C;

2), the NMR spectrum characteristics of the compound:

With deuterated dimethyl sulfoxide as the solvent and TMS as the internal standard, the peaks are assigned as follows: ¹ H NMR (500MHz, DMSO-d ₆ ) δ: 11.54 (s, 1H, NH), 8.12 (d, 1H, J =9.0Hz), 7.87 (d, 2H, J=8.0Hz), 7.22 (s, 1H), 7.00-7.05 (m, 3H), 6.96 (d, 1H, J=8.0Hz), 6.89 (d, 1H , J=8.0Hz), 6.73-6.83 (m, 2H), 6.46 (t, 1H, J=9.0Hz), 6.04 (s, 2H, -OCH ₂ O-), 3.83 (s, 3H, -OCH ₃ ）； ¹³ CNMR（125MHz，DMSO-d ₆ ）δ:162.18，161.88，149.05，147.86，147.41，139.44，135.20，131.07，129.39，128.48，126.75，125.37，122.19，113.59，108.39，105.32，101.14，55.32。

3) High-resolution mass spectrometry characteristics of the compound:

Ionization by electrospray: Calcd for C ₂₀ H ₁₈ N ₂ O ₄ ([M+Na] ⁺ ), 373.1158; Found, 373.1162.

The physicochemical properties of compound 14 are as follows:

1), pale yellow solid, melting point 106°C;

2), the NMR spectrum characteristics of the compound:

With deuterated dimethyl sulfoxide as the solvent and TMS as the internal standard, the peaks are assigned as follows: ¹ H NMR (400MHz, DMSO-d ₆ ) δ: 11.63 (s, 1H, NH), 8.13 (d, 1H, J =10.0Hz), 7.41-7.47 (m, 3H), 7.23 (d, 1H, J=0.8Hz), 7.14 (d, 1H, J=8.8Hz), 6.96-7.07 (m, 2H), 6.90 (d , 1H, J=8.0Hz), 6.75-6.85 (m, 2H), 6.46-6.52 (m, 1H), 6.05 (s, 2H, -OCH ₂ O-), 3.82 (s, 3H, -OCH ₃ ) .

The physicochemical properties of compound 15 are as follows:

1), yellow solid, melting point 216-217°C;

2), the NMR spectrum characteristics of the compound:

With deuterated dimethyl sulfoxide as the solvent and TMS as the internal standard, the peaks are assigned as follows: ¹ H NMR (400MHz, DMSO-d ₆ ) δ: 11.53 (s, 1H, NH), 8.13 (d, 1H, J =9.6Hz), 7.53-7.55 (m, 1H), 7.46 (d, 1H, J=1.6Hz), 7.23 (s, 1H), 6.96-7.08 (m, 3H), 6.90 (m, 1H), 6.74 -6.84 (m, 2H), 6.46-6.52 (m, 1H), 6.05 (s, 2H, -OCH ₂ O-), 3.83 (s, 6H, -OCH ₃ ).

The physicochemical properties of compound 16 are as follows:

1), yellow solid;

2), the NMR spectrum characteristics of the compound:

With deuterated dimethyl sulfoxide as the solvent and TMS as the internal standard, the peaks are assigned as follows: ¹ H NMR (400MHz, DMSO-d ₆ ) δ: 11.44 (s, 0.15H, NH), 11.28 (s, 0.75H , NH), 7.95 (d, 0.8H, J=9.6Hz), 7.72 (d, 0.16H, J=9.6Hz), 7.59-7.61 (m, 0.81H), 7.45-7.49 (m, 0.8H), 7.34-7.39 (m, 0.16H), 7.19-7.23 (m, 1H), 7.12 (d, 1H, J=8.0Hz), 6.89-7.07 (m, 4.16H), 6.66-6.85 (m, 2H), 6.45-6.51 (m, 0.8H ₎ , 6.14-6.20 (m _, 0.16H), 6.04 (s, 1.6H, -OCH2O-), 6.02 (s, 0.32H, -OCH2O-), 4.11- 4.16 (m, 1.5H), 4.00-4.05 (m, 0.3H), 1.36 (t, 2.5H, J=6.8Hz), 1.18 (t, 0.5H, J=6.8Hz).

The physicochemical properties of compound 17 are as follows:

1) Light yellow solid, melting point 220-221°C;

2), the NMR spectrum characteristics of the compound:

With deuterated dimethyl sulfoxide as the solvent and TMS as the internal standard, the peaks are assigned as follows: ¹ H NMR (400MHz, DMSO-d ₆ ) δ: 11.70 (s, 1H, NH), 8.12 (d, 1H, J =9.6Hz), 7.95-7.98 (m, 2H), 7.34 (t, 2H, J=8.8Hz), 7.23 (s, 1H), 6.96-7.07 (m, 2H), 6.90-6.92 (m, 1H) , 6.75-6.87 (m, 2H), 6.46-6.52 (m, 1H), 6.05 (s, 2H, _-OCH2O- ).

The physicochemical properties of compound 18 are as follows:

1), pale yellow solid, melting point 216-218°C;

2), the NMR spectrum characteristics of the compound:

With deuterated dimethyl sulfoxide as the solvent and TMS as the internal standard, the peaks are assigned as follows: ¹ H NMR (400MHz, DMSO-d ₆ ) δ: 11.73 (s, 1H, NH), 8.13 (d, 1H, J =9.6Hz), 7.68-7.75 (m, 2H), 7.55-7.60 (m, 1H), 7.42-7.47 (m, 1H), 7.23 (d, 1H, J=0.8Hz), 6.97-7.08 (m, 2H), 6.72-6.92 (m, 3H), 6.46-6.52 (m, 1H), 6.05 (s, 2H, _-OCH2O- ).

The physicochemical properties of compound 19 are as follows:

1), light yellow solid, melting point 226-228 ℃;

2), the NMR spectrum characteristics of the compound:

With deuterated dimethyl sulfoxide as the solvent and TMS as the internal standard, the peaks are assigned as follows: ¹ H NMR (500MHz, DMSO-d ₆ ) δ: 11.74 (s, 1H, NH), 8.13 (d, 1H, J =9.5Hz), 7.93 (s, 1H), 7.84 (d, 1H, J=7.5Hz), 7.65 (d, 1H, J=7.5Hz), 7.54 (t, 1H, J=7.5Hz), 7.22 ( s, 1H), 7.01-7.06 (m, 1H), 6.97 (d, 1H, J=8.0Hz), 6.90 (d, 1H, J=7.5Hz), 6.76-6.87 (m, 2H), 6.47-6.52 (m, 1H), 6.05 (s, 2H, -OCH ₂ O-); ¹³ C NMR (125MHz, DMSO-d ₆ ) δ: 161.30, 150.20, 147.87, 147.49, 140.26, 135.65, 135.32, 133.16, 131.41, 131.00, 130.38, 128.15, 127.18, 126.66, 126.32, 122.30, 108.40, 105.35, 101.16.

3) High-resolution mass spectrometry characteristics of the compound:

Ionization by electrospray: Calcd for C ₁₉ H ₁₅ ClN ₂ O ₃ ([M+H] ⁺ ), 353.0687; Found, 353.0689.

The physicochemical properties of compound 20 are as follows:

1), pale yellow solid;

2), the NMR spectrum characteristics of the compound:

With deuterated dimethyl sulfoxide as the solvent and TMS as the internal standard, the peaks are assigned as follows: ¹ H NMR (500MHz, DMSO-d ₆ ) δ: 11.80 (s, 0.35H, NH), 11.74 (s, 0.65H , NH), 7.94 (d, 0.65H, J=9.5Hz), 7.76 (d, 0.35H, J=10.0Hz), 7.39-7.57 (m, 4H), 7.23 (s, 0.65H), 7.12 (s , 0.35H), 6.68-7.07 (m, 5H), 6.44-6.49 (m, 0.65H), 6.14-6.19 (m, 0.35H), 6.02 (d, 2H, J=11.5Hz, -OCH ₂ O- ）； ¹³ C NMR（125MHz，DMSO-d ₆ ）δ:168.22，162.10，149.75，147.85，147.79，147.48，147.37，146.62，140.37，139.54，135.86，135.67，135.16，135.06，131.25，130.95，130.31，130.26 ,129.61,129.55,129.20,128.89,128.47,127.96,127.87,127.15,126.80,126.63,126.58,122.35,122.06,108.39,105.30,105.20,101.15.

The physical and chemical properties of compound 21 are as follows:

1), pale yellow solid, melting point 186°C;

2), the NMR spectrum characteristics of the compound:

With deuterated dimethyl sulfoxide as the solvent and TMS as the internal standard, the peaks are assigned as follows: ¹ H NMR (400MHz, DMSO-d ₆ ) δ: 9.45 (s, 1H, NH), 7.76 (d, 1H, J =9.6Hz), 7.61 (s, 2H), 7.16 (d, 1H, J=1.6Hz), 6.87-6.97 (m, 3H), 6.55-6.65 (m, 2H), 6.35-6.41 (m, 1H) , 6.03 (s, 2H, _-OCH2O- ).

The physical and chemical properties of compound 22 are as follows:

1), pale yellow solid, melting point 240°C;

2), the NMR spectrum characteristics of the compound:

With deuterated dimethyl sulfoxide as the solvent and TMS as the internal standard, the peaks are assigned as follows: ¹ H NMR (500MHz, DMSO-d ₆ ) δ: 11.89 (s, 1H, NH), 8.77-8.78 (m, 2H ), 8.14 (d, 1H, J=9.5Hz), 7.79-7.80 (m, 2H), 7.24 (s, 1H), 6.77-7.08 (m, 5H), 6.47-6.52 (m, 1H), 6.05 ( s, 2H, -OCH ₂ O-); ¹³ C NMR (125MHz, DMSO-d ₆ ) δ: 161.77, 151.39, 150.77, 149.98, 148.45, 148.11, 141.30, 140.93, 136.46, 131.52, 128.55, 127.19, 123.45 122.96, 121.97, 108.98, 105.91, 101.75.

3) High-resolution mass spectrometry characteristics of the compound:

Ionization by electrospray: Calcd for C ₁₈ H ₁₅ N ₃ O ₃ ([M+H] ⁺ ), 322.1199; Found, 322.1193.

The physical and chemical properties of compound 23 are as follows:

1), pale yellow solid, melting point 226°C;

2), the NMR spectrum characteristics of the compound:

With deuterated dimethyl sulfoxide as the solvent and TMS as the internal standard, the peaks are assigned as follows: ¹ H NMR (500MHz, DMSO-d ₆ ) δ: 11.84 (s, 1H, NH), 9.04 (s, 1H), 8.75-8.76 (m, 1H), 8.22 (d, 1H, J=7.5Hz), 8.12 (d, 1H, J=9.5Hz), 7.55 (t, 1H, J=7.0Hz), 7.24 (s, 1H ), 6.76-7.08 (m, 5H), 6.47-6.52 (m, 1H), 6.05 (s, 2H, -OCH ₂ O-); ¹³ C NMR (125MHz, DMSO-d ₆ ) δ: 161.29, 152.12, 150.23, 148.44, 147.86, 147.49, 140.39, 135.70, 135.30, 130.97, 129.06, 128.07, 126.64, 123.47, 122.34, 108.40, 105.32, 101.16.

3) High-resolution mass spectrometry characteristics of the compound:

Ionization by electrospray: Calcd for C ₁₈ H ₁₅ N ₃ O ₃ ([M+H] ⁺ ), 322.1186; Found, 322.1188.

The physical and chemical properties of compound 24 are as follows:

1), orange solid, melting point 204-206°C;

2), the NMR spectrum characteristics of the compound:

With deuterated dimethyl sulfoxide as the solvent and TMS as the internal standard, the peaks are assigned as follows: ¹ H NMR (500MHz, DMSO-d ₆ ) δ: 11.70 (s, 1H, NH), 7.87-8.12 (m, 3H ), 7.23 (s, 2H), 7.01-7.06 (m, 1H), 6.97 (d, 1H, J=8.0Hz), 6.90 (d, 1H, J=8.0Hz), 6.75-6.86 (m, 2H) , 6.46-6.50 (m, 1H), 6.05 (s, 2H, -OCH ₂ O-); ¹³ C NMR (125MHz, DMSO-d ₆ ) δ: 157.36, 149.38, 147.85, 147.45, 145.52, 139.95, 139.58, 138.23, 135.47, 134.64, 134.35, 131.69, 131.00, 128.73, 128.21, 128.00, 127.69, 126.67, 122.27, 108.40, 105.30, 101.14.

3) High-resolution mass spectrometry characteristics of the compound:

Ionization by electrospray: Calcd for C ₁₇ H ₁₄ N ₂ O ₃ S ([M+H] ⁺ ), 327.0791; Found, 327.0793.

The physicochemical properties of compound 25 are as follows:

1), pale yellow solid;

2), the NMR spectrum characteristics of the compound:

With deuterated dimethyl sulfoxide as the solvent and TMS as the internal standard, the peaks are assigned as follows: ¹ H NMR (400MHz, DMSO-d ₆ ) δ: 11.84 (s, 0.64H, NH), 11.74 (s, 0.37H , NH), 7.76-8.11 (m, 2H), 7.20-7.24 (m, 2H), 6.74-7.10 (m, 5H), 6.44-6.56 (m, 1H), 6.04 (s, 2H, _-OCH2O -).

3) High-resolution mass spectrometry characteristics of the compound:

Ionization by electrospray: Calcd for C ₁₇ H ₁₃ ClN ₂ O ₃ S ([M+Na] ⁺ ), 383.0234; Found, 383.0230.

The physical and chemical properties of compound 26 are as follows:

1), pale yellow solid;

2), the NMR spectrum characteristics of the compound:

With deuterated dimethyl sulfoxide as the solvent and TMS as the internal standard, the peaks are assigned as follows: ¹ H NMR (400MHz, DMSO-d ₆ ) δ: 11.83 (s, 0.64H, NH), 11.73 (s, 0.34H , NH), 7.70-8.10 (m, 2H), 7.20-7.40 (m, 2H), 6.74-7.11 (m, 5H), 6.44-6.57 (m, 1H), 6.04 (s, 2H, _-OCH2O -); HRMS (ESI).

3) High-resolution mass spectrometry characteristics of the compound:

Ionization by electrospray: Calcd for C ₁₇ H ₁₃ BrN ₂ O ₃ S ([M+Na] ⁺ ), 426.9715; Found, 426.9719.

The physical and chemical properties of compound 27 are as follows:

1) Light yellow solid, melting point 157-159°C;

2), the NMR spectrum characteristics of the compound:

With deuterated dimethyl sulfoxide as the solvent and TMS as the internal standard, the peaks are assigned as follows: ¹ H NMR (500MHz, DMSO-d ₆ ) δ: 11.35 (s, 1H, NH), 7.81 (d, 2H, J =7.5Hz), 7.60-7.68 (m, 4H), 7.16 (s, 1H), 6.88-6.94 (m, 3H), 6.67-6.73 (m, 2H), 6.23-6.28 (m, 1H), 6.03 ( s, 2H, -OCH ₂ O-); ¹³ C NMR (125MHz, DMSO-d ₆ ) δ: 149.20, 147.82, 147.45, 139.80, 138.98, 135.50, 132.88, 130.91, 129.12, 127.39, 126.98, 126.41, 122.18 108.38, 105.29, 101.13.

3) High-resolution mass spectrometry characteristics of the compound:

Ionization by electrospray: Calcd for C ₁₈ H ₁₆ N ₂ O ₄ S ([M+H] ⁺ ), 357.0904; Found, 357.0906,

The physicochemical properties of compound 28 are as follows:

1), pale yellow solid, melting point 172°C;

2), the NMR spectrum characteristics of the compound:

With deuterated dimethyl sulfoxide as the solvent and TMS as the internal standard, the peaks are assigned as follows: ¹ H NMR (500MHz, DMSO-d ₆ ) δ: 11.25 (s, 1H, NH), 7.69 (d, 2H, J =8.0Hz), 7.59 (d, 1H, J=9.5Hz), 7.39 (d, 2H, J=7.5Hz), 7.15 (s, 1H), 6.88-6.94 (m, 3H), 6.67-6.72 (m , 2H), 6.22-6.27 (m, 1H), 6.03 (s, 2H, -OCH ₂ O-), 2.07 (s, 3H, -CH ₃ ); ¹³ C MR (125MHz, DMSO-d ₆ ) δ: 149.00, 147.82, 147.44, 143.27, 139.66, 136.11, 135.43, 130.92, 129.54, 127.46, 127.04, 126.43, 122.16, 108.38, 105.30, 101.13, 20.90.

The physical and chemical properties of compound 29 are as follows:

1), yellow solid, melting point 157-158°C;

2), the NMR spectrum characteristics of the compound:

With deuterated dimethyl sulfoxide as the solvent and TMS as the internal standard, the peaks are assigned as follows: ¹ H NMR (400MHz, DMSO-d ₆ ) δ: 11.29 (s, 1H, NH), 7.72 (d, 2H, J =8.0Hz), 7.60 (d, 1H, J=9.6Hz), 7.43 (d, 2H, J=8.4Hz), 7.16 (d, 1H, J=1.6Hz), 6.88-6.95 (m, 3H), 6.67-6.74 (m, 2H), 6.22-6.29 (m, 1H), 6.03 (s, 2H, -OCH ₂ O-), 2.65 (q, 2H, J=7.6Hz), 1.17 (t, 3H, J =7.6Hz).

The physicochemical properties of compound 30 are as follows:

1), yellow solid, melting point 140-142°C;

2), the NMR spectrum characteristics of the compound:

With deuterated dimethyl sulfoxide as the solvent and TMS as the internal standard, the peaks are assigned as follows: ¹ H NMR (400MHz, DMSO-d ₆ ) δ: 11.19 (s, 1H, NH), 7.72-7.76 (m, 2H ), 7.59 (d, 1H, J=9.6Hz), 7.17 (d, 1H, J=1.2Hz), 7.11-7.14 (m, 2H), 6.88-6.95 (m, 3H), 6.67-6.74 (m, 2H), 6.22-6.28 (m, 1H), 6.03 (s, 2H, _-OCH2O- ), 3.83 (s, 3H).

The physicochemical properties of compound 31 are as follows:

1), yellow solid, melting point 152-154°C;

2), the NMR spectrum characteristics of the compound:

With deuterated dimethyl sulfoxide as the solvent and TMS as the internal standard, the peaks are assigned as follows: ¹ H NMR (400MHz, DMSO-d ₆ ) δ: 11.44 (s, 1H, NH), 7.83-7.86 (m, 2H ), 7.73-7.76 (m, 2H), 7.62 (d, 1H, J=9.6Hz), 7.17 (d, 1H, J=1.6Hz), 6.89-6.95 (m, 3H), 6.69-6.77 (m, 2H), 6.23-6.29 (m, 1H), 6.04 (s, 2H, _-OCH2O- ).

The physicochemical properties of compound 32 are as follows:

1), yellow solid, melting point 174-176°C;

2), the NMR spectrum characteristics of the compound:

With deuterated dimethyl sulfoxide as the solvent and TMS as the internal standard, the peaks are assigned as follows: ¹ H NMR (400MHz, DMSO-d ₆ ) δ: 11.64 (s, 1H, NH), 8.50-8.54 (m, 2H ), 8.23-8.26 (m, 1H), 7.92 (t, 1H, J=8.0Hz), 7.65 (d, 1H, J=10.0Hz), 7.17 (d, 1H, J=1.2Hz), 6.88-6.96 (m, 3H), 6.69-6.79 (m, 2H), 6.23-6.29 (m, 1H), 6.03 (s, 2H, _-OCH2O- ).

The physicochemical properties of compound 33 are as follows:

1), red solid, melting point 186-188°C;

2), the NMR spectrum characteristics of the compound:

With deuterated dimethyl sulfoxide as the solvent and TMS as the internal standard, the peaks are assigned as follows: ¹ H NMR (400MHz, DMSO-d ₆ ) δ: 11.37 (s, 0.66H, NH), 11.35 (s, 0.33H , NH), 8.46 (s, 0.66H), 8.42 (s, 0.33H), 8.34 (d, 0.66H, J=9.6Hz), 7.89-7.934 (m, 1H), 7.62 (d, 0.33H, J =9.6Hz), 7.22(s, 0.66H), 7.16(s, 0.33H), 6.68-7.07(m, 6H), 6.48-6.56(m, 0.66H), 6.24-6.30(m, 0.33H), 6.05 (s, 1.34H, _-OCH2O- ), 6.03 (s, 0.66H, _-OCH2O- ).

Embodiment 2: bioassay experiment

1. Insects to be tested: armyworm larvae in the early 3rd instar, provided by the insect breeding room of the Pollution-free Pesticide Research Center of Northwest A&F University.

2. Samples and reagents:

The samples are: toosendanin, piperine acid, piperine ester, piperine alcohol, piperine aldehyde and compound 1-33 prepared in the examples. The solvent was acetone, analytically pure, from Chengdu Kelong Chemical Reagent Factory.

3. Bioassay method:

Using the method of adding small leaf butterfly: spread a layer of filter paper on the bottom of a petri dish with a diameter of 9 cm, and add water to moisturize it. Pick 10 3rd instar prophase armyworm larvae with the same size and robustness from each dish. Weigh 5 mg of toosendanin, piperine acid, piperine ester, piperine alcohol, piperine aldehyde and compound 1-33 prepared in the examples and add 5 ml of acetone to prepare a drug solution with a concentration of 1 mg/ml. Cut the oat leaves into 1×1 cm leaflets, soak them in the liquid to be tested for 3 seconds, dry them and feed them to the test insects. Acetone solution was used as the blank control group. For each treatment of 10 heads, repeat 3 times. Breed at room temperature (around 25°C), humidity 65% to 80%, and light time 12 hours/12 hours. After 48 hours, normal leaf butterflies were fed until eclosion. Regularly record the food intake, live population, and symptoms of the insects, and calculate the 24-hour and 48-hour food refusal rates and final mortality of the insects according to the following formula. The measurement results are shown in Table 1.

Food rejection rate (%) = (average food intake of the control group - average food intake of the treatment group) / (average food intake of the control group) × 100

Final mortality rate (%) = (death number of test insects) / (total number of test insects) × 100

Adjusted mortality rate (%) = (treatment mortality rate - control mortality rate) / (1 - control mortality rate) × 100

Table 1: Antifeeding and killing effects of piperine hydrazone/acylhydrazone/sulfonyl hydrazone derivatives 1-33 on 3rd instar armyworm

in conclusion:

The results showed that the compounds (2, 9, 17, 20, 31, 15, 16, 17, 20) had higher poisonous activity than the commercialized toosendanin at 34 days, so they are expected to be used in the preparation of high-efficiency, environmentally friendly , low toxicity botanical pesticides.

Claims (3)

1. piperine hydrazone/acylhydrazone/sulphonyl hydrazone analog derivative, is characterized in that, its chemical general formula is:

In formula, R is respectively:

2. the preparation method of piperine hydrazone/acylhydrazone/sulphonyl hydrazone analog derivative claimed in claim 1, it is characterized in that, by hydrolysis, esterification, reduction and oxidation obtain piperine aldehyde, then react with substituted phenylhydrazines/hydrazides/sulfonyl hydrazide respectively, obtain serial piperine hydrazone/acylhydrazone/sulphonyl hydrazone analog derivative, specifically follow these steps to preparation:

By a certain amount of piperine aldehyde and corresponding substituted phenylhydrazines/hydrazides/sulfonyl hydrazide anhydrous alcohol solution, in backward above-mentioned solution, drip two Glacial acetic acid, be heated to reflux, TLC follows the tracks of detection, after reaction finishes, after concentrating, separate to obtain required sterling by preparation silica gel thin sheet;

Described substituted phenylhydrazines/hydrazides/sulfonyl hydrazide is respectively:

A, phenylhydrazine class: ortho-nitrophenyl hydrazine, paranitrophenylhydrazine, 2,3,5,6-tetrafluoro phenylhydrazine;

B, hydrazides class: acethydrazide, cyano acethydrazide, benzoyl hydrazine, to toluyl hydrazine, between toluyl hydrazine, adjacent toluyl hydrazine, para hydroxybenzene formyl hydrazine, p-nitrobenzoylhydrazide, m-nitro formyl hydrazine, to methoxybenzoyl hydrazine, meta-methoxy benzoyl hydrazine, 3, 4-dimethoxy benzoyl hydrazine, O-ethoxyl formyl hydrazine, to fluorobenzoyl hydrazine, between fluorobenzoyl hydrazine, m-chloro benzoyl hydrazine, adjacent chlorobenzoyl hydrazine, 2, 4, 6-trichlorobenzene formyl hydrazine, cigarette hydrazine, vazadrine, 2-thenoyl hydrazine, the chloro-2-thenoyl of 5-hydrazine, the bromo-2-thenoyl of 5-hydrazine,

C, sulfonyl hydrazines: benzol sulfohydrazide, p-toluene sulfonyl hydrazide, to ethylbenzene sulfonyl hydrazide, to anisole sulfonyl hydrazide, brosyl hydrazine, m-nitro sulfonyl hydrazide, to chlorine m-nitro sulfonyl hydrazide.

3. piperine hydrazone/acylhydrazone/sulphonyl hydrazone analog derivative claimed in claim 1 is for the preparation of the application of plant insecticide.

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