Morpholine-containing amide compound as well as preparation method and application thereof

Abstract

The invention belongs to the field of fruit and vegetable preservation and agricultural sterilization, and provides a morpholine-containing amide compound as well as a preparation method and application thereof. According to the method, N-(2-aminoethyl) morpholine and organic acid with different heterocyclic structures are mainly used as raw materials and are subjected to amidation reaction in a dry organic solvent under the catalytic action of a condensing agent, so that the morpholine-containing amide compound is generated. The preparation process is simple and convenient to operate, safe and environment-friendly, the product yield is as high as 87%, and a remarkable tyrosinase inhibition effect and good bactericidal activity are shown.

Description

Technical Field

[0001] The invention belongs to the field of fruit and vegetable preservation and agricultural sterilization, and particularly relates to an amide compound containing morpholine and a preparation method and application thereof. Background Art

[0002] Tyrosinase, also known as polyphenol oxidase, is widely found in plants and animals such as apples, mushrooms and humans, and also in microorganisms such as molds. Tyrosinase is a key rate-limiting enzyme in the biosynthesis of melanin, which can catalyze the hydroxylation of monophenols to o-diphenols and further catalyze the oxidation of o-diphenols to o-quinones to form melanin, which can cause browning of fruits, vegetables and some aquatic products, thereby reducing the shelf life and market value of food.

[0003] Tyrosinase inhibitors can reduce the production of melanin by reducing the catalytic efficiency of tyrosinase. Nowadays, tyrosinase inhibitors come from a wide range of sources, including natural plant extracts, microbial sources, and chemical synthesis. Currently, commonly used tyrosinase inhibitors include arbutin, vitamin C, ascorbic acid, hydroquinone, polyphenols, aromatic alcohols, etc., but these additives have problems such as low timeliness, poor stability, poor safety, and high cost in long-term use. Therefore, it is of great significance to develop safe, non-toxic, stable, and highly active tyrosinase inhibitors.

[0004] The morpholine ring has nitrogen and oxygen atoms, which are easy to chelate Cu ions in tyrosinase, and are easy to form hydrogen bonds in the body, participate in physiological processes, and have good biocompatibility. Morpholine compounds have diverse biological activities, such as bactericidal, antioxidant, anti-browning, antiviral, etc., and play a vital role in the fields of medicine, food, and agricultural sterilization. Summary of the invention

[0005] In order to solve the above technical problems, the present invention provides an amide compound containing morpholine. The compound has a simple structure, mild synthesis reaction conditions, simple operation and high yield.

[0006] The technical solution of the present invention is:

[0007] The present invention provides an amide compound containing morpholine, the general structural formula of which is:

[0008]

[0009] Wherein, R is any one of the following: pyrazole ring, pyrimidine ring, benzopyran ring and derivatives thereof;

[0010] Preferably, the general structural formula is:

[0011]

[0012] Among them, R 1 , R2 , R 3 , R 4 Any one selected from -H, -OH, -OR, -R, -CX3, -CHX2, -CH2X, -X.

[0013] The present invention also provides a method for preparing an amide compound containing morpholine, comprising the following steps:

[0014] Reagent I and reagent II are dissolved in organic solvent A, and a condensing agent is added, and the mixture is stirred at room temperature for 10 to 18 hours for reaction. After the reaction is completed, the mixture is washed and dried, and then extracted with organic solvent C. After purification by column chromatography, an amide compound containing morpholine is obtained, which is recorded as compound III.

[0015] Wherein, reagent I is a morpholine derivative;

[0016] Reagent II is an organic acid;

[0017] The organic solvent A is selected from any one of dichloromethane, 1,2-dichloroethane, ether, tetrahydrofuran, acetonitrile and toluene;

[0018] The organic solvent C is selected from any one of dichloromethane, ethyl acetate, diethyl ether and cyclohexane.

[0019] Preferably, reagent I is N-(2-aminoethyl)morpholine;

[0020] Reagent II is selected from any one of 3-(difluoromethyl)-1H-pyrazole-4-carboxylic acid, 3-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid, 4-pyrimidinecarboxylic acid, 2-cyclopropyl-6-hydroxypyrimidine-4-carboxylic acid, 2-chloropyrimidine-4-carboxylic acid, and 2-oxo-2H-benzopyran-3-carboxylic acid, but is not limited to the above types, and can also be other organic acids;

[0021] The condensing agent is composed of condensing agent I and condensing agent II, wherein the molar ratio of condensing agent I to condensing agent II is 1 to 3:1;

[0022] The condensing agent is selected from any one of the following: condensing agent I is 4-dimethylaminopyridine, condensing agent II is dicyclohexylcarbodiimide;

[0023] Alternatively, the condensing agent I is dicyclohexylcarbodiimide, and the condensing agent II is 4-dimethylaminopyridine;

[0024] Alternatively, the condensing agent I is 1-hydroxybenzotriazole, and the condensing agent II is 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride;

[0025] Alternatively, the condensing agent I is 2-(7-azobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate, and the condensing agent II is N,N-diisopropylethylamine;

[0026] The organic solvent C is selected from any one of dichloromethane, ethyl acetate, acetone and cyclohexane;

[0027] The developing solvent used in the column chromatography is selected from any two of methanol, ethyl acetate and dichloromethane, wherein the volume ratio of methanol:ethyl acetate is: (1-3):(1-6); or the volume ratio of methanol:dichloromethane is 4:1.

[0028] Preferably, the molar ratio of reagent I to reagent II is 1:1.2-2.

[0029] Preferably, the molar ratio of reagent I: reagent II: condensing agent is 1:1:1.5-4; the millimolar volume ratio of reagent II to organic solvent A is 1 mmol:3-10 mL.

[0030] The application of the morpholine-containing amide compounds provided by the present invention in the preparation of fruit and vegetable fresh-keeping products and the application of the amide compounds in the preparation of agricultural fungicide products are also the key protected contents of the present invention.

[0031] Compared with the prior art, the present invention has the following advantages and effects:

[0032] (1) The morpholine-containing amide compounds provided by the present invention have a simple structure;

[0033] (2) The synthesis method of the morpholine-containing amide compound provided by the present invention is simple, has mild reaction conditions, high yield, and is easy to industrialize;

[0034] (3) The morpholine-containing amide compounds provided by the present invention have good tyrosinase inhibitory activity and have good application value in the preservation of fruits and vegetables;

[0035] (4) The amide compounds containing morpholine provided by the present invention also have good bactericidal activity and have potential application value in agricultural sterilization. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] Figure 1 is a flow chart of the preparation method;

[0037] Figure 2 is the molecular structure formula of compound IIIa-IIIf;

[0038] Figure 3 is the hydrogen spectrum of IIIa in Example 1 ( 1 H NMR, 400 MHz, CDCl3);

[0039] Figure 4 is the carbon spectrum of IIIa in Example 1 ( 13 C NMR, 101 MHz, CDCl3);

[0040] Figure 5 is the mass spectrum of IIIa in Example 1;

[0041] Figure 6 is the hydrogen spectrum of IIIb in Example 1 ( 1 H NMR, 400 MHz, CDCl3);

[0042] Figure 7 is the carbon spectrum of IIIb in Example 1 ( 13 C NMR, 101 MHz, CDCl3);

[0043] Figure 8 is the mass spectrum of IIIb in Example 1;

[0044] Fig. 9 is the hydrogen spectrum of IIIc in Example 1 ( 1 H NMR, 400 MHz, CDCl3);

[0045] Fig.10 is the carbon spectrum of IIIc in Example 1 ( 13 C NMR, 101 MHz, CDCl3);

[0046] Fig.11 is the mass spectrum of IIIc in Example 1;

[0047] Fig.12 is the hydrogen spectrum of IIId in Example 1 ( 1 H NMR, 400 MHz, DMSO);

[0048] Fig.13 is the carbon spectrum of IIId in Example 1 ( 13 C NMR, 101 MHz, DMSO);

[0049] Fig.14 is the mass spectrum of IIId in Example 1;

[0050] Fig.15 is the hydrogen spectrum of IIIe in Example 1 ( 1 H NMR, 400 MHz, DMSO);

[0051] Fig.16 is the carbon spectrum of IIIe in Example 1 ( 13 C NMR, 101 MHz, DMSO);

[0052] Fig.17 is the mass spectrum of IIIe in Example 1;

[0053] Fig.18 is the hydrogen spectrum of IIIf in Example 1 ( 1 HNMR, 400 MHz, CDCl3);

[0054] Fig.19 is the carbon spectrum of IIIf in Example 1 ( 13 C NMR, 101 MHz, CDCl3);

[0055] Fig. 20 This is the mass spectrum of IIIf in Example 1. DETAILED DESCRIPTION

[0056] In order to enable those skilled in the art to better understand the present invention, the present invention is further described in conjunction with specific implementation methods.

[0057] The drugs involved in the present invention were purchased from: Shanghai McLean Biochemical Technology Co., Ltd., Shanghai Anage Chemical Co., Ltd., Beijing Bailingwei Technology Co., Ltd., Shanghai Aladdin Biochemical Technology Co., Ltd., and Tianjin Kaitong Chemical Reagent Co., Ltd.

[0058] Example 1 Preparation and characterization of morpholine-containing amide compounds

[0059] (1) Reagents

[0060] Table 1 Reagent names and abbreviations

[0061]

[0062]

[0063] (2) Yield calculation method:

[0064] Yield = actual yield / theoretical yield × 100%

[0065] Preparation and synthesis of the morpholine-containing amide compounds of the present invention ( Figure 2 Compounds IIIa~IIIf) were obtained and the products were characterized.

[0066] 1.1 Preparation and characterization of compound IIIa

[0067] like Figure 1 As shown in the flow chart, 1.162 g (6.6 mmol) of 3-(difluoromethyl)-1H-pyrazole-4-carboxylic acid was added to a 100 mL round-bottom flask, 0.859 g (6.6 mmol) of N-(2-aminoethyl)morpholine was added, 25 mL of dry dichloromethane, 1.64 g (8.56 mmol) of EDCI, and 0.4 g (3.3 mmol) of DMAP were added in sequence, and stirred at room temperature for 12 h. The reaction solution was washed with water, dried over anhydrous sodium sulfate, extracted with dichloromethane, and purified by column chromatography after solvent removal. The developing solvent for column chromatography was methanol: EA (volume ratio of 3:1). A light orange solid was obtained with a yield of 61%; the melting range was 84°C to 85°C.

[0068] The data of H NMR spectrum, C NMR spectrum and mass spectrum of compound IIIa are as follows Figure 2 to Figure 4 As shown:

[0069] 1 H NMR (400MHz, CDCl3) δ (ppm) 7.89 (s, 1H, NH), 6.85 (t, J = 54.1Hz, 1H, Pyrazole-H), 3.87 (s, 3H, CH3), 3.67 (t, J = 4.7Hz, 4H ,Nam-CH2),3.45(q,J=5.6Hz,2H,CH2),2.82(s,1H,Nam-CH),2.51(t,J=6.0Hz,2H,CH2),2.45(t,J=4.7Hz,4H,Nam-CH2). 13 C NMR(101MHz, CDCl3)δ(ppm)161.20,142.94,134.83,116.75,113.83,111.51,109.19,66.82,56.51,53.14,39.43,35.92.IR(KBr)νcm -1 :3360(NH),1636(C=O),1557(C=N),1271(CN); HRMS(ESI)calcd for[M+H] + :C 12 H 19 N4O2F2:289.1476,found289.1480.

[0070] 1.2 Preparation and characterization of compound IIIb

[0071] Take 6.6mmol of 3-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid in a 100mL round-bottom flask, add 0.859g (6.6mmol) of N-(2-aminoethyl)morpholine, add 25mL of dry dichloromethane, 1.64g (8.56mmol) EDCI, 0.4g (3.3mmol) DMAP in turn, and stir at room temperature for 12h. The reaction solution was washed with water, dried over anhydrous sodium sulfate, extracted with dichloromethane, and purified by column chromatography after solvent removal. The developing solvent for column chromatography was methanol: EA (volume ratio of 3:1). Orange-yellow solid, yield: 61%, melting range 95℃-96℃;

[0072] The data of H NMR spectrum, C NMR spectrum and mass spectrum of compound IIIb are as follows Figure 5 to Figure 7 As shown:

[0073] 1H NMR (400MHz, CDCl3) δ (ppm) 7.96 (s, 1H, NH), 6.87 (s, 1H, Pyrazole-H), 3.96 (s, 3H, CH3), 3.72 (d, J= 4.6Hz, 4H, Nam-CH2), 3.51 (s, 2H, CH2), 2.56 (t, J=5.9Hz, 2H, CH2), 2.49 (t, J=4.6Hz, 4H, Nam-CH2). 13 C NMR(101MHz, CDCl3)δ(ppm)160.32,135.73,122.39,119.72,117.46,66.86(2C),56.30,53.13(2C),39.75,35.94.IR(KBr)νcm -1 :3242(NH),1639(C=O),1573(C=N),1232(CN); HRMS(ESI)calcd for[M+H] + :C 12 H 18 N4O2F3:307.1382, found 307.1387.

[0074] 1.3 Preparation and characterization of compound IIIc

[0075] Take 3mmol of 4-pyrimidinecarboxylic acid in a 100mL round-bottom flask, add 0.391g (3mmol) of N-(2-aminoethyl)morpholine, add 25mL of dry dichloromethane, 0.958g (5mmol) EDCI, 0.611g (5mmol) DMAP in turn, and stir at room temperature for 16h. The reaction solution is washed with water, dried over anhydrous sodium sulfate, extracted with dichloromethane, and purified by column chromatography after solvent removal. The developing solvent for column chromatography is methanol: EA (volume ratio is 1:1). A yellow solid is obtained with a yield of 55.4%; the melting range is 89℃~90℃.

[0076] The data of H NMR spectrum and C NMR mass spectrum of compound IIIc are as follows:

[0077] 1 H NMR(400MHz,DMSO-d6)δ(ppm)9.33(s,1H,Pyrim-H),9.06(s,1H,Pyrim-H),8.92(d,J=5.9Hz,1H,NH),8.03(dd,J=5.1,1 .4Hz,1H,Pyrim-H),3.57(t,J=4.6Hz,4H,Nam-CH2),3.47(m,2H,CH2),2.51(m,2H,CH2),2.41(t,J=4.6Hz,4H,Nam-CH2);13 C NMR(151MHz,DMSO-d6)δ(ppm)162.83,160.14,158.33,156.82,118.90,66.67(2C),57.40,53.63(2C),36.52.IR(KBr)νcm -1 :3242(NH),1639(C=O),1573(C=N),1232(CN); HRMS(ESI)calcd for[M+H] + :C 11 H 16 N4O2:237.1352, found 237.1355.

[0078] 1.4 Preparation and characterization of compound IIId

[0079] Take 6.6mmol of 2-cyclopropyl-6-hydroxypyrimidine-4-carboxylic acid in a 100mL round-bottom flask, add 0.859g (6.6mmol) of N-(2-aminoethyl)morpholine, add 25mL of dry dichloromethane, 1.64g (8.56mmol) EDCI, 0.4g (3.3mmol) DMAP in sequence, and stir at room temperature for 18h. The reaction solution was washed with water, dried over anhydrous sodium sulfate, extracted with dichloromethane, and purified by column chromatography after solvent removal. The developing solvent for column chromatography was methanol:EA (volume ratio of 3:1). Pale yellow solid, yield 67.3%; melting range 195℃~196℃;

[0080] The data of H NMR spectrum, C NMR spectrum and mass spectrum of compound IIId are as follows:

[0081] 1 H NMR (400MHz, DMSO-d6) δ (ppm) 12.87 (s, 1H, OH) 8.48 (s, 1H, NH), 6.56 (s, 1H, Pyrim-H), 3.64 (d, J = 26.4 Hz,4H,Nam-CH2),3.33(s,2H,CH2),2.50(m,6H,Nam-CH2),1.97(s,1H,Cpr-CH),1.49(m,4H,Cpr-CH2); 13 CNMR(101MHz,DMSO)δ(ppm)165.19,163.34,162.63,154.81,109.72,66.81(2C),56.92,53.48(2C),39.35,36.10,13.92,10.67.IR(KBr)νcm -1 :3366(NH),1658(C=O),

[0082] 1509(C=N),1113(CN); HRMS(ESI)calcd for[M+H] + :C 14 H 21 N4O3:293.1614; found293.1618.

[0083] 1.5 Preparation and characterization of compound IIIe

[0084] Take 3mmol of 2-chloropyrimidine-4-carboxylic acid in a 100mL round-bottom flask, add 0.391g (3mmol) of N-(2-aminoethyl)morpholine, add 25mL of dry dichloromethane, 0.611g (5mmol) EDCI, 0.611g (5mmol) DMAP in turn, and stir at room temperature for 14h. The reaction solution was washed with water, dried over anhydrous sodium sulfate, extracted with dichloromethane, and purified by column chromatography after solvent removal. The developing solvent for column chromatography was methanol: EA (volume ratio of 1:6). Pale yellow solid, yield 51.8%; melting range 86℃~87℃;

[0085] The data of H NMR spectrum, C NMR spectrum and mass spectrum of compound IIIe are as follows:

[0086] 1 H NMR (400MHz, DMSO-d6) δ (ppm) 9.01 (s, 1H, Pyrim-H), 8.92 (s, 1H, NH), 8.02 (d, J = 6.5Hz, 1H, Pyrim-H),3.56(s,4H,Nam-CH2),3.18(s,2H,CH2),2.49(s,4H,Nam-CH2),2.42(s,2H,CH2). 13 C NMR(101MHz,DMSO-d6)δ(ppm)163.42,161.67,160.68,160.34,118.21,66.73,66.61,57.31,57.12,53.59,53.51.HRMS(ESI)calcd for[M+H] + :C 11 H 15 ClN4O2:291.0962; found 291.0965.

[0087] 1.6 Preparation and characterization of compound IIIf

[0088] Take 6mmol of 2-oxo-2H-benzopyran-3-carboxylic acid in a 100mL round-bottom flask, add 0.781g (6mmol) of N-(2-aminoethyl)morpholine, add 25mL of dry dichloromethane, 1.917g (10mmol) EDCI, 0.773g (6mmol) DMAP in sequence, and stir at room temperature for 18h. The reaction solution was washed with water, dried over anhydrous sodium sulfate, extracted with ethyl acetate, and purified by column chromatography after solvent removal. The developing solvent for column chromatography was methanol: EA (volume ratio of 1:1). Pale yellow solid, yield 87.3%; melting range 147℃~148℃;

[0089] The data of H NMR spectrum, C NMR spectrum and mass spectrum of compound IIIf are as follows:

[0090] 1 H NMR (400MHz, CDCl3) δ (ppm) 9.01 (s, 1H, Ccr-1H), 8.90 (s, 1H, NH), 7.74-7.65 (m, 2H, Ph-2H), 7.39 (dd, J=12.2, 7.9Hz, 2H, P h-2H),3.77-3.74(m,4H,Nam-CH2),3.59(q,J=6.0Hz,2H,CH2),2.61(t,J=6.3Hz,2H,CH2),2.53(t,J=4.6Hz,4H,Nam-CH2). 13 C NMR(101MHz,CDCl3)δ(ppm)161.46,161.28,154.46,148.13,134.00,129.80,12 5.26,118.67,118.64,116.63,67.07(2C),56.81(2C),53.43,36.66.IR(KBr)νcm -1 :3323(NH),1689(C=O),1540(C=N),1240(CN); HRMS(ESI)calcd for[M+H] + :C 16 H 18 N2O4:291.0962; found303.1350.

[0091] Example 2

[0092] 2.1 Tyrosinase inhibitory activity assay

[0093] Dissolve the compounds IIIa-IIIf in Example 1 in DMSO and dilute with PBS to prepare solutions of different concentrations (see Table 1 for the concentrations of the solutions). Add 20 μL of solution, 30 μL of tyrosinase (200 U / mL) and 100 μL of phosphate buffer (50 mmol / L, pH = 6.8) to each well of a 96-well plate. After incubation at 25°C for 20 min, add 50 μL of L-DOPA (2 mmol / L) as a substrate. Mix the solution thoroughly and then incubate at 25°C for 10 min. Finally, measure the absorbance at 475 nm using an enzyme reader. Use DMSO as a blank control and kojic acid as a positive control. Repeat the experiment three times. The inhibition rate calculation formula is:

[0094] Inhibition rate (%) = (1-ΔAsample / ΔAcontrol) × 100%,

[0095] Among them, ΔAsample is the absorbance of the sample containing the target compound;

[0096] ΔAcontrol is the absorbance of DMSO control.

[0097] The activity test results are shown in Table 1:

[0098] Table 2 Tyrosinase inhibitory activity of target compounds IIIa-IIIf

[0099]

[0100] The results showed that this series of compounds showed good tyrosinase inhibitory activity and concentration inhibitory effect, and can be used for fruit and vegetable preservation and production of related products.

[0101] 2.2 Bactericidal activity

[0102] Experimental method: Each test compound IIIa-IIIf in Example 1 was dissolved in DMSO to form a 1% Tween 80-DMSO stock solution for use. The mycelium growth method was used to evaluate the indoor fungicidal activity of the test compounds IIIa-IIIf against the test target at a dose of 50 mg / L and 100 mg / L, with DMSO as a control.

[0103] The antibacterial rate calculation formula is as follows:

[0104]

[0105] The activity test results are shown in Table 2:

[0106] Table 3 Bactericidal activity of compounds IIIa-IIIf

[0107]

[0108] Experiments show that the six compounds IIIa-IIIf all exhibit certain fungicidal activity. For example, at 50 mg / L, the inhibition rates of compounds IIIa, IIIe and IIIf against four pathogens, namely, Sclerotinia sclerotiorum, Botrytis cinerea, Penicillium citrinum and Sclerotinia sclerotiorum, all reached more than 50%; at 100 mg / L, the inhibition rates of IIIa, IIIe and IIIf against Sclerotinia sclerotiorum were higher than 70%, and the inhibition rates against Botrytis cinerea were around 60%, while the inhibition rates against Penicillium citrinum were all over 50%, and the inhibition rates against Sclerotinia sclerotiorum were around 60%. They can be used to prepare fungicides and other products.

[0109] Example 3-Example 6

[0110] Compound IIIa was prepared according to the reagents in the following table. Other reagents and amounts used in the preparation process and other experimental steps were the same as the preparation steps of compound IIIa in Example 1.

[0111] Table 4 Reagents involved in the reactions in Examples 3-6

[0112]

[0113] In summary, the present invention provides an amide compound containing morpholine and a preparation method thereof. The method mainly uses N-(2-aminoethyl)morpholine and an organic acid with different heterocyclic structures as raw materials, and an amidation reaction occurs in a dry organic solvent through the catalytic action of a condensation agent, thereby generating an amide compound containing morpholine. The preparation process is simple to operate, safe and environmentally friendly, the product yield is as high as 87%, and it exhibits significant tyrosinase inhibition and good bactericidal activity.

[0114] The above are only preferred embodiments of the present invention, and are not intended to limit the patent scope of the present invention. All equivalent changes and modifications made within the scope of the present invention should still fall within the scope of the present invention.

Claims

1. A morpholine-containing amide compound, characterized in that: The general structural formula of the compound is: Wherein, R is any one of the following: pyrazole ring, pyrimidine ring, benzopyran ring and derivatives thereof.

2. A method for preparing a morpholine-containing amide compound as described in claim 1, comprising the following steps: Reagent I and reagent II are dissolved in organic solvent A, and a condensing agent is added, and the mixture is stirred at room temperature for 10 to 18 hours for reaction. After the reaction is completed, the mixture is washed and dried, and then extracted with organic solvent C. After purification by column chromatography, an amide compound containing morpholine is obtained, which is recorded as compound III. in, Reagent Ⅰ is a morpholine derivative; Reagent II is an organic acid; The organic solvent A is selected from any one of dichloromethane, 1,2-dichloroethane, ether, tetrahydrofuran, acetonitrile and toluene; The organic solvent C is selected from any one of dichloromethane, ethyl acetate, diethyl ether and cyclohexane.

3. A method for preparing a morpholine-containing amide compound as described in claim 2, characterized in that: Reagent I is N-(2-aminoethyl)morpholine; Reagent II is selected from any one of 3-(difluoromethyl)-1H-pyrazole-4-carboxylic acid, 3-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid, 4-pyrimidinecarboxylic acid, 2-cyclopropyl-6-hydroxypyrimidine-4-carboxylic acid, 2-chloropyrimidine-4-carboxylic acid, and 2-oxo-2H-benzopyran-3-carboxylic acid; The condensing agent is composed of condensing agent I and condensing agent II, wherein the molar ratio of condensing agent I to condensing agent II is 1 to 3:1; The condensing agent is selected from any one of the following: condensing agent I is 4-dimethylaminopyridine, condensing agent II is dicyclohexylcarbodiimide; Alternatively, the condensing agent I is dicyclohexylcarbodiimide, and the condensing agent II is 4-dimethylaminopyridine; Alternatively, the condensing agent I is 1-hydroxybenzotriazole, and the condensing agent II is 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride; Alternatively, the condensing agent I is 2-(7-azobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate, and the condensing agent II is N,N-diisopropylethylamine; The developing solvent used in the column chromatography is selected from any two of methanol, ethyl acetate and dichloromethane, wherein the volume ratio of methanol:ethyl acetate is: (1-3):(1-6); or the volume ratio of methanol:dichloromethane is 4:

1.

4. A method for preparing a morpholine-containing amide compound as claimed in claim 2, characterized in that: The molar ratio of reagent I to reagent II is 1:1.2-2.

5. A method for preparing a morpholine-containing amide compound as claimed in claim 2, characterized in that: The molar ratio of reagent I: reagent II: condensing agent is 1:1:1.5-4; the millimolar volume ratio of reagent II to organic solvent A is 1mmol:3-10mL.

6. Use of the morpholine-containing amide compound according to claim 1 in the preparation of fruit and vegetable fresh-keeping products.

7. Use of the morpholine-containing amide compound according to claim 1 in the preparation of agricultural fungicide products.

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