Andrographolide diester derivative as well as preparation method and application thereof

Abstract

The invention discloses andrographolide diester derivatives as well as a preparation method and application thereof. The structural general formula of the series of andrographolide diester derivatives is as shown in formula I in the specification. Researches show that in the andrographolide diester derivative disclosed by the invention, the insecticidal activity of part of compounds on oriental armyworm is equivalent to that of commercial botanical pesticide toosendanin, and even higher than that of toosendanin; part of the compounds have good contact activity on aphis citricola wingless adult aphids and tetranychus cinnabarinus female adult mites, and compared with parent andrographolide, the contact activity of the compounds is remarkably improved. The method can be used for preparing efficient, environment-friendly and low-toxicity botanical pesticides. # imgabs0 #

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and in particular relates to an andrographolide diester derivative, a preparation method and an application thereof. Background Art

[0002] Andrographolide, also known as andrographolide, is a diterpene lactone active ingredient extracted from the Acanthaceae plant Andrographis paniculata (Burm.f.) Nees. Because of its wide range of pharmacological activities, it is also known as a natural antibiotic.

[0003]

[0004] Andrographolide and its derivatives have a variety of medical and agricultural biological activities. In medicine, they have anti-cancer [Journal of Natural Medicines, 2024, 78, 123-145; Chemistry of Natural Compounds, 2020, 56, 264-269], anti-inflammatory [Pharmacological Research, 2023, 194, 106861; Integrative Medicine Research, 2023, 12, 100944], antibacterial [Microbiology Spectrum, 2023, 11, e0297822; Heliyon, 2021, 7, e07002] and antiviral [Molecular Biology Reports, 2023, 50, 4261-4272; Phytomedicine, 2023, 112, 154708] and other activities. In terms of agricultural activity, andrographolide and its derivatives also have good biological activity. For example, insecticidal activity [Molecules, 2021, 26, 5982; Bioorganic Chemistry, 2019, 86, 28-33], acaricidal activity [Journal of Agricultural and Food Chemistry, 2020, 68, 4131-4143] and aphidicidal activity [Advanced Agrochem, 2023, 2, 349-355].

[0005] There are also many reports on the structural modification of andrographolide. For example, Hao et al. used the Fischer-indole rearrangement reaction to synthesize a series of novel indole andrographolide derivatives, some of which have good contact activity against Tetranychus cinnabarinus and Aphid cinnabarinus [Advanced Agrochem, 2023, 2, 349-355]. In addition, Kumar et al. synthesized C-17 ester derivatives of andrographolide by strategies such as epoxidation and ring opening. The antitumor activity of the synthesized compounds against breast cancer (MCF-7), colon cancer (HCT-116), lung cancer (A549) and prostate cancer (PC-3) cells was determined, and it was found that some derivatives were more sensitive to lung cancer (A549) and prostate cancer (PC-3) cell lines [ACS Omega, 2023, 8, 6099-6123]. Summary of the invention

[0006] In view of the defects or shortcomings of the prior art, the object of the present invention is to provide an andrographolide diester derivative, a preparation method and application.

[0007] To this end, the chemical structural formula of the andrographolide diester derivative provided by the present invention is as shown in Formula I:

[0008]

[0009] in:

[0010] R is selected from alkyl, phenyl, substituted phenyl, benzyl, cinnamyl, substituted cinnamyl, pyridyl or substituted pyridyl.

[0011] An optional solution is that R in Formula I is selected from: (1) R = CH3; (2) R = (CH2)2CH3; (3)

[0012] R=(CH2)4CH3; (4)R=(CH2)6CH3; (5)R=(CH2)7CH3; (6)R=(CH2)8CH3; (7)

[0013] R=(CH2)9CH3;(8)R=(CH2) 10CH3; (9) R = phenyl; (10) R = 2-fluorophenyl; (11) R = 3-fluorophenyl; (12) R = 4-fluorophenyl; (13) R = 2-chlorophenyl; (14) R = 3-chlorophenyl; (15) R = 4-chlorophenyl; (16) R = 2-bromophenyl; (17) R = 4-bromophenyl; (18) R = 3-cyanophenyl; (19) R = 4-cyanophenyl; (20) R = 2-nitrophenyl; (21) R = 3-nitrophenyl; (22 )R=4-nitrophenyl; (23)R=2-trifluoromethylphenyl; (24)R=3-trifluoromethylphenyl; (25)R=4-trifluoromethylphenyl; (26)R=2-methylphenyl; (27)R=3-methylphenyl; (28)R=4-methylphenyl; (29)R=3-methoxyphenyl; (30)R=4-methoxyphenyl; (31)R=3,4-(methylenedioxy)phenyl; (32)R=3,4-(ethylenedioxy)phenyl; (3 3) R = 2-methoxy-5-fluorophenyl; (34) R = 3,5-dimethylphenyl; (35) R = benzyl; (36) R = cinnamyl; (37) R = 4-fluorocinnamyl; (38) R = 4-chlorocinnamyl; (39) R = 4-bromocinnamyl; (40) R = 4-nitrocinnamyl; (41) R = 4-trifluoromethylcinnamyl; (42) R = 4-methylcinnamyl; (43) R = 4-methoxycinnamyl; (44) R = 3,4-(ethylene) (45) R = 4-pyridyl; (46) R = 3-pyridyl; (47) R = 2-fluoro-3-pyridyl; (48) R = 2-chloro-3-pyridyl; (49) R = 2-bromo-3-pyridyl; (50) R = 2-methoxy-3-pyridyl; (51) R = 6-fluoro-3-pyridyl; (52) R = 6-chloro-3-pyridyl; (53) R = 6-bromo-3-pyridyl; or (54) R = 6-methoxy-3-pyridyl.

[0014] The present invention also provides a method for preparing the above compound, which comprises the following steps:

[0015] Step 1, reacting andrographolide of formula (a) with aluminum oxide to obtain an intermediate of formula (b);

[0016]

[0017] Step 2, reacting the intermediate represented by formula (b) with tert-butyldimethylsilyl chloride to prepare the intermediate represented by formula (c);

[0018]

[0019] Step 3, the intermediate represented by formula (c) is reduced with lithium aluminum tetrahydride to prepare the intermediate represented by formula (d);

[0020]

[0021] Step 4: The intermediate represented by formula (d) reacts with RCOOH to obtain andrographolide diester derivatives.

[0022] An optional scheme is that the reaction in step 1 is carried out in a first organic solvent at a reaction temperature of 105-125° C. The first organic solvent may be pyridine.

[0023] An optional solution is that the reaction in step 2 is carried out in a second organic solvent, and a first organic base is added at the same time, and the reaction temperature is 55-65° C. The second organic solvent may be N,N-dimethylformamide, and the first organic base may be imidazole.

[0024] An optional solution is that the reaction in step 3 is carried out in a third organic solvent at a reaction temperature of -5 to 5° C. The third organic solvent may be tetrahydrofuran.

[0025] An optional scheme is that the reaction in step 4 is carried out in a fourth organic solvent, and a condensing agent and a second organic base are added at the same time, and the reaction temperature is 20 to 30° C. The fourth organic solvent can be selected from dichloromethane. The condensing agent can be selected from 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride. The second organic base can be selected from 4-dimethylaminopyridine.

[0026] An optional scheme is that RCOOH in the step 4 is selected from acetic acid, butyric acid, hexanoic acid, octanoic acid, nonanoic acid, decanoic acid, undecanoic acid, dodecanoic acid, benzoic acid, 2-fluorobenzoic acid, 3-fluorobenzoic acid, 4-fluorobenzoic acid, 2-chlorobenzoic acid, 3-chlorobenzoic acid, 4-chlorobenzoic acid, 2-bromobenzoic acid, 4-bromobenzoic acid, 3-cyanobenzoic acid, 4-cyanobenzoic acid, 2-nitrobenzoic acid, 3-nitrobenzoic acid, 4-nitrobenzoic acid, 2-trifluoromethylbenzoic acid, 3-trifluoromethylbenzoic acid, 4-trifluoromethylbenzoic acid, 2-methylbenzoic acid, 3-methylbenzoic acid, 4-methylbenzoic acid, 3-methoxybenzoic acid Benzoic acid, 4-methoxybenzoic acid, 3,4-(methylenedioxy)benzoic acid, 3,4-(ethylenedioxy)benzoic acid, 2-methoxy-5-fluorobenzoic acid, 3,5-dimethylbenzoic acid, phenylacetic acid, cinnamic acid, 4-fluorocinnamic acid, 4-chlorocinnamic acid, 4-bromocinnamic acid, 4-nitrocinnamic acid, 4-trifluoromethylcinnamic acid, 4-methylcinnamic acid, 4-methoxycinnamic acid, 3,4-(ethylenedioxy)cinnamic acid, isonicotinic acid, nicotinic acid, 2-fluoronicotinic acid, 2-chloronicotinic acid, 2-bromonicotinic acid, 2-methoxynicotinic acid, 6-fluoronicotinic acid, 6-chloronicotinic acid, 6-bromonicotinic acid or 6-methoxynicotinic acid.

[0027] The andrographolide diester derivatives of the present invention can be used to prepare botanical pesticides, and some of the compounds have good biological activity against common agricultural pests such as oriental armyworm, apple yellow aphid and cinnabarinus spider mite, and their activity is significantly improved compared with the parent andrographolide, and can be used to prepare high-efficiency, environmentally friendly and low-toxic botanical pesticides. In addition, the preparation method of the compound of the present invention has a simple process, high yield and low cost. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 is the H NMR spectrum of compound 6;

[0029] Figure 2 is the H NMR spectrum of compound 12;

[0030] Figure 3 is the H NMR spectrum of compound 27;

[0031] Figure 4 This is the H NMR spectrum of compound 37. DETAILED DESCRIPTION

[0032] Unless otherwise specified, the scientific and technical terms used herein are understood according to the knowledge of ordinary technicians in the relevant fields.

[0033] The following are specific examples of the present invention. It should be noted that the present invention is not limited to the following specific examples, and all equivalent changes made on the basis of the technical solution of this application fall within the protection scope of the present invention. The reaction raw materials and chemical reagents used in the following examples are all commercially available products.

[0034] The synthetic route of the andrographolide diester derivatives of the present invention is schematically shown as follows:

[0035]

[0036] First, andrographolide (a) is dissolved in a suitable solvent (such as pyridine), and then a suitable amount of aluminum oxide is added to the solution, and an intermediate represented by formula (b) is prepared under suitable conditions (such as an oil bath at about 115° C.);

[0037] Secondly, the intermediate represented by formula (b) is reacted with an appropriate amount of TBSCl (tert-butyldimethylsilyl chloride) and an organic base (such as imidazole) in a suitable solvent (such as N,N-dimethylformamide) and conditions (such as an oil bath at about 60° C.) to obtain the intermediate represented by formula (c);

[0038] Subsequently, the intermediate represented by formula (c) reacts with an appropriate amount of lithium aluminum tetrahydride in a suitable solvent (such as tetrahydrofuran) and under suitable conditions (such as about 0° C.) to obtain the intermediate represented by formula (d);

[0039] Finally, the intermediate represented by formula (d) reacts with an appropriate amount of RCOOH in a suitable reaction system (such as a reaction system in the presence of EDCI (1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride), DMAP (4-dimethylaminopyridine) and dry dichloromethane) and reaction conditions (such as a reaction temperature of 20-30° C.) to obtain the compound of the present invention.

[0040] Example 1: Preparation of andrographolide diester (1-54) derivatives

[0041] Preparation of the intermediate represented by formula (b): Andrographolide (1.0 mmol) and aluminum oxide (0.6 mmol) were dissolved in 5 mL of pyridine, followed by stirring in an oil bath at 115° C. for 12 hours; after the reaction was complete, the filtrate was filtered, washed, and concentrated, and then separated by column chromatography to obtain intermediate b in a yield of 45%.

[0042] Preparation of the intermediate represented by formula (c): The intermediate represented by formula (b) (1.0 mmol), TBSCl (4.0 mmol) and imidazole (5.0 mmol) were dissolved in 5 mDMF, and then placed in a 60°C oil bath and stirred for 5 hours; after the reaction was complete, 10 mL of water was added, and dichloromethane (20 mL×3) was used for extraction. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, concentrated, and separated by column chromatography to obtain intermediate c with a yield of 70%.

[0043] Preparation of the intermediate represented by formula (d): The intermediate represented by formula (c) (1.0 mmol) was dissolved in 5 mL of tetrahydrofuran and stirred in an ice bath to dissolve; then lithium aluminum tetrahydride (1.0 mmol) was added in batches and the reaction was continued under stirring in an ice bath for 15 minutes; after the reaction was complete, 10 mL of ice water was added and extracted with ethyl acetate (20 mL×3); the organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, concentrated and separated by column chromatography to obtain intermediate d with a yield of 45%.

[0044] Preparation method of target compound 1-54: Dissolve the intermediate represented by formula (d) (0.18 mmol), RCOOH (0.45 mmol), EDCI (0.45 mmol) and DMAP (0.04 mmol) in 5 mL of dry dichloromethane and stir at room temperature for 8-22 hours; after the reaction is complete, add ethyl acetate (30 mL) to dilute, then add 0.1 M hydrochloric acid aqueous solution, 5% sodium bicarbonate aqueous solution and saturated brine to wash in sequence, dry and concentrate the organic phase, separate by thin layer chromatography to obtain target compound 1-54 in a yield of 5-43%.

[0045] The compounds 1-54 prepared by the above preparation method have the following general formulae and correspond to compounds having structures (1)-(54), respectively.

[0046]

[0047] (1): R=CH3; (2): R= (CH2)2CH3; (3): R= (CH2)4CH3; (4): R= (CH2)6CH3; (5): R= (CH2)7CH3; (6): R= (CH2)8CH3; (7): R= (CH2)9CH3; (8): R= (CH2) 10 CH3; (9): R = phenyl; (10): R = 2-fluorophenyl; (11): R = 3-fluorophenyl; (12): R = 4-fluorophenyl; (13): R = 2-chlorophenyl; (14): R = 3-chlorophenyl; (15): R = 4-chlorophenyl; (16): R = 2-bromophenyl; (17): R = 4-bromophenyl; (18): R = 3-cyanophenyl; (19): R = 4-cyanophenyl; (20): R = 2-nitrophenyl; (21): R = 3-nitrophenyl; ( 22): R = 4-nitrophenyl; (23): R = 2-trifluoromethylphenyl; (24): R = 3-trifluoromethylphenyl; (25): R = 4-trifluoromethylphenyl; (26): R = 2-methylphenyl; (27): R = 3-methylphenyl; (28): R = 4-methylphenyl; (29): R = 3-methoxyphenyl; (30): R = 4-methoxyphenyl; (31): R = 3,4-(methylenedioxy)phenyl; (32): R = 3,4-(ethylenedioxy)phenyl; (33): R = 2-methoxy-5-fluorophenyl; (34): R = 3,5-dimethylphenyl; (35): R = benzyl; (36): R = cinnamyl; (37): R = 4-fluorocinnamyl; (38): R = 4-chlorocinnamyl; (39): R = 4-bromocinnamyl; (40): R = 4-nitrocinnamyl; (41): R = 4-trifluoromethylcinnamyl; (42): R = 4-methylcinnamyl; (43): R = 4-methoxycinnamyl; (44): R = 3,4-(2-(2-methyl-2-oxo-cinnamyl)) ethyldioxy)cinnamyl; (45): R = 4-pyridyl; (46): R = 3-pyridyl; (47): R = 2-fluoro-3-pyridyl; (48): R = 2-chloro-3-pyridyl; (49): R = 2-bromo-3-pyridyl; (50): R = 2-methoxy-3-pyridyl; (51): R = 6-fluoro-3-pyridyl; (52): R = 6-chloro-3-pyridyl; (53): R = 6-bromo-3-pyridyl; (54): R = 6-methoxy-3-pyridyl.

[0048] The physicochemical properties of compound 1 are as follows:

[0049] 1) Colorless liquid; Yield: 25%

[0050] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0051] IR cm -1 (KBr): 2956, 2856, 1742, 1607, 1468, 1399, 1269, 1099; 1 HNMR (400MHz, CDCl3) δ: 5.61-5.54 (m, 1H), 5.20-5.06 (m, 1H), 4.72-4.71 (m, 1H), 4.48-4 .44(m, 1H), 4.16-3.97(m, 4H), 3.92-3.89(m, 1H), 3.61-3.58(m, 1H), 3.28-3.24(m, 1H), 2.58-2.49(m, 1H), 2.39-2.35(m, 1H), 2.22-2.18(m, 1H), 2.04-2.02(m, 6H), 1.92-1.73( m, 4H), 1.65-1.45 (m, 4H), 1.13-0.99 (m, 5H), 0.90-0.81 (m, 21H), 0.03-(-0.01) (m, 12H).

[0052] The physicochemical properties of compound 2 are as follows:

[0053] 1) Colorless liquid; Yield: 27%

[0054] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0055] IR cm -1 (KBr): 2955, 2859, 1739, 1607, 1466, 1252, 1099; 1 HNMR (400MHz, CDCl3) δ: 5.61-5.54 (m, 1H), 5.22-5.12 (m, 1H), 4.72-4.71 (m, 1H), 4.48-4.44 ( m, 1H), 4.18-3.95 (m, 4H), 3.92-3.90 (m, 1H), 3.61-3.58 (m, 1H), 3.29-3.25 (m, 1H), 2.59-2.5 0 (m, 1H), 2.40-2.35 (m, 1H), 2.29-2.19 (m, 5H), 1.93-1.73 (m, 4H), 1.69-1.60 (m, 5H), 1.52-1 .42(m, 3H), 1.10-0.99(m, 5H), 0.97-0.91(m, 6H), 0.87-0.86(m, 21H), 0.03-(-0.01)(m, 12H).

[0056] The physicochemical properties of compound 3 are as follows:

[0057] 1) Colorless liquid; Yield: 28%

[0058] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0059] IR cm -1 (KBr): 2858, 1738, 1608, 1470, 1400, 1262, 1104; 1 HNMR (400MHz, CDCl3) δ: 5.60-5.54 (m, 1H), 5.21-5.12 (m, 1H), 4.72-4.71 (m, 1H), 4.48-4.44 (m, 1H), 4.16-4 .11(m, 1H), 4.08-4.02(m, 1H), 3.99-3.98(m, 2H), 3.92-3.89(m, 1H), 3.61-3.58(m, 1H), 3.28-3.24(m, 1H), 2.58-2.51(m, 1H), 2.39-2.35(m, 1H), 2.30-2.25(m, 4H), 2.22-2.18(m, 1H), 1.93-1.73(m, 4H), 1.65-1.60( m, 4H), 1.58-1.42 (m, 4H), 1.31-1.27 (m, 8H), 1.10-0.99 (m, 5H), 0.91-0.86 (m, 27H), 0.03-(-0.01) (m, 12H).

[0060] The physicochemical properties of compound 4 are as follows:

[0061] 1) Colorless liquid; Yield: 25%

[0062] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0063] IR cm -1 (KBr): 2939, 2859, 1739, 1639, 1464, 1367, 1252, 1097; 1HNMR (400MHz, CDCl3) δ: 5.60-5.54 (m, 1H), 5.20-5.11 (m, 1H), 4.72-4.71 (m, 1H), 4.47-4.44 (m, 1H), 4.17-4 .10(m, 1H), 4.08-4.01(m, 1H), 3.99-3.97(m, 2H), 3.92-3.89(m, 1H), 3.61-3.58(m, 1H), 3.28-3.24(m, 1H), 2 .58-2.49(m, 1H), 2.39-2.35(m, 1H), 2.30-2.25(m, 4H), 2.22-2.18(m, 1H), 1.93-1.73(m, 4H), 1.64-1.61(m , 4H), 1.57-1.42(m, 4H), 1.31-1.23(m, 16H), 1.10-0.99(m, 5H), 0.87-0.85(m, 27H), 0.03-(-0.01)(m, 12H).

[0064] The physicochemical properties of compound 5 are as follows:

[0065] 1) Colorless liquid; Yield: 29%

[0066] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0067] IR cm -1 (KBr): 2931, 2856, 1739, 1555, 1464, 1363, 1097; 1 HNMR (400MHz, CDCl3) δ: 5.60-5.54 (m, 1H), 5.21-5.11 (m, 1H), 4.73-4.71 (m, 1H), 4.48-4.44 (m, 1H), 4.17-4 .11(m, 1H), 4.08-4.01(m, 1H), 3.99-3.97(m, 2H), 3.92-3.89(m, 1H), 3.61-3.58(m, 1H), 3.28-3.24(m, 1H), 2 .58-2.49(m, 1H), 2.39-2.35(m, 1H), 2.30-2.25(m, 4H), 2.22-2.18(m, 1H), 1.93-1.73(m, 4H), 1.65-1.60(m , 4H), 1.56-1.42(m, 4H), 1.28-1.25(m, 20H), 1.12-0.99(m, 5H), 0.89-0.86(m, 27H), 0.03-(-0.01)(m, 12H).

[0068] The physicochemical properties of compound 6 are as follows:

[0069] 1) Colorless liquid; Yield: 25%

[0070] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0071] IR cm -1 (KBr): 2930, 2857, 1739, 1555, 1251, 1097; 1 HNMR (400MHz, CDCl3) δ: 5.60-5.55 (m, 1H), 5.21-5.12 (m, 1H), 4.72-4.70 (m, 1H), 4.48-4.44 (m, 1H), 4. 17-4.11 (m, 1H), 4.08-4.01 (m, 1H), 3.99-3.97 (m, 2H), 3.93-3.89 (m, 1H), 3.61-3.58 (m, 1H), 3.28-3.24 (m, 1H), 2.58-2.50 (m, 1H), 2.40-2.35 (m, 1H), 2.30-2.18 (m, 5H), 1.90-1.74 (m, 4H), 1.66-1.61 (m, 4H) , 1.55-1.42(m, 4H), 1.29-1.25(m, 24H), 1.10-0.99(m, 5H), 0.89-0.85(m, 27H), 0.03-(-0.01)(m, 12H).

[0072] The physicochemical properties of compound 7 are as follows:

[0073] 1) Colorless liquid; Yield: 32%

[0074] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0075] IR cm -1 (KBr): 2929, 2856, 1739, 1555, 1465, 1363, 1251, 1097; 1HNMR (400MHz, CDCl3) δ: 5.60-5.54 (m, 1H), 5.20-5.11 (m, 1H), 4.72-4.71 (m, 1H), 4.48-4.44 (m, 1H), 4. 17-4.10 (m, 1H), 4.08-4.01 (m, 1H), 3.99-3.97 (m, 2H), 3.92-3.89 (m, 1H), 3.61-3.58 (m, 1H), 3.28-3.24 (m, 1H), 2.58-2.49 (m, 1H), 2.39-2.35 (m, 1H), 2.30-2.18 (m, 5H), 1.93-1.73 (m, 4H), 1.65-1.58 (m, 4H) , 1.56-1.42(m, 4H), 1.29-1.25(m, 28H), 1.10-0.99(m, 5H), 0.88-0.85(m, 27H), 0.03-(-0.01)(m, 12H).

[0076] The physicochemical properties of compound 8 are as follows:

[0077] 1) Colorless liquid; Yield: 24%

[0078] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0079] IR cm -1 (KBr): 2944, 2858, 1726, 1638, 1459, 1370, 1103; 1 HNMR (400MHz, CDCl3) δ: 5.60-5.54(m, 1H), 5.21-5.12(m, 1H), 4.72-4.71(m, 1H), 4.48-4.44( m, 1H), 4.17-4.02 (m, 2H), 3.99-3.89 (m, 3H), 3.61-3.58 (m, 1H), 3.28-3.24 (m, 1H), 2.58-2.49 (m, 1H), 2.40-2.35 (m, 1H), 2.30-2.19 (m, 5H), 2.01-1.71 (m, 5H), 1.59-1.56 (m, 4H), 1.50-1. 43(m, 3H), 1.29-1.25(m, 32H), 1.10-0.99(m, 5H), 0.89-0.86(m, 27H), 0.03-(-0.01)(m, 12H).

[0080] The physicochemical properties of compound 9 are as follows:

[0081] 1) White solid, melting point: 88-89°C; yield: 21%

[0082] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0083] IR cm -1 (KBr): 3095, 3077, 1732, 1558, 1366, 1127; 1 HNMR (400MHz, CDCl3) δ: 8.05-8.02 (m, 4H, Ar-H), 7.58-7.53 (m, 2H, Ar-H), 7.45-7.40 (m, 4H, Ar-H), 5.71-5.64 ( m, 1H), 5.42-5.25 (m, 1H), 4.71 (s, 0.53H), 4.64 (s, 0.47H), 4.50-4.43 (m, 2H), 4.32-4.23 (m, 3H), 3.90-3.83 (m , 1H), 3.59-3.54(m, 1H), 3.26-3.16(m, 1H), 2.87-2.78(m, 1H), 2.37-2.33(m, 1H), 2.26-2.21(m, 1H), 2.14-2.0 2(m, 1H), 1.92-1.71(m, 4H), 1.56-1.37(m, 3H), 1.06-0.96(m, 5H), 0.88-0.80(m, 21H), 0.03-(-0.02)(m, 12H).

[0084] The physicochemical properties of compound 10 are as follows:

[0085] 1) White solid, melting point: 72-73°C; yield: 28%

[0086] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0087] IR cm -1 (KBr): 3093, 1733, 1556, 1258; 1HNMR (400MHz, CDCl3) δ: 7.95-7.90 (m, 2H, Ar-H), 7.54-7.48 (m, 2H, Ar-H), 7.22-7.09 (m, 4H, Ar-H), 5.71-5.64 (m, 1H), 5.37-5.24 (m, 1H), 4.68 (s, 0.4H), 4.63 (s, 0.6H), 4.52-4.42 (m, 2H), 4.40-4.23 (m, 3H), 3.90-3.83 (m, 1H), 3.59-3.54(m, 1H), 3.26-3.17(m, 1H), 2.87-2.79(m, 1H), 2.37-2.32(m, 1H), 2.25-2.20(m, 1H), 2.14-1.9 9(m, 1H), 1.92-1.71(m, 4H), 1.49-1.33(m, 3H), 1.10-0.96(m, 5H), 0.88-0.80(m, 21H), 0.02-(-0.03)(m, 12H).

[0088] The physicochemical properties of compound 11 are as follows:

[0089] 1) Colorless liquid; Yield: 31%

[0090] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0091] IR cm -1 (KBr): 2859, 1732, 1607, 1400, 1265; 1 HNMR (400MHz, CDCl3) δ: 7.83-7.80 (m, 2H, Ar-H), 7.72-7.68 (m, 2H, Ar-H), 7.43-7.39 (m, 2H, Ar-H), 7.28-7.27 (m, 1H, Ar-H) , 7.24-7.22 (m, 1H, Ar-H), 5.71-5.63 (m, 1H), 5.37-5.23 (m, 1H), 4.70 (s, 0.54H), 4.65 (s, 0.46H), 4.50-4.41 (m, 2H), 4.39-4 .24(m, 3H), 3.90-3.84(m, 1H), 3.59-3.54(m, 1H), 3.26-3.17(m, 1H), 2.85-2.74(m, 1H), 2.38-2.33(m, 1H), 2.26-2.21(m, 1 H), 2.12-1.98(m, 1H), 1.91-1.72(m, 4H), 1.51-1.31(m, 3H), 1.09-0.96(m, 5H), 0.89-0.81(m, 21H), 0.03-(-0.02)(m, 12H).

[0092] The physicochemical properties of compound 12 are as follows:

[0093] 1) Colorless liquid; Yield: 29%

[0094] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0095] IR cm -1 (KBr): 3089, 1726, 1556, 1370, 1273, 852; 1 HNMR (400MHz, CDCl3) δ: 8.06-8.01 (m, 4H, Ar-H), 7.12-7.06 (m, 4H, Ar-H), 5.70-5.63 (m, 1H), 5.36-5.24 (m, 1H), 4.70 (s, 0.42H), 4.63 (m, 0.58H), 4.48-4.41 (m, 2H), 4.37-4.21 (m, 3H), 3.90-3.84 (m, 1H), 3.60- 3.54(m, 1H), 3.26-3.17(m, 1H), 2.85-2.74(m, 1H), 2.37-2.33(m, 1H), 2.26-2.20(m, 1H), 2.11-2.00(m, 1H), 1.92-1.70(m, 4H), 1.61-1.31(m, 3H), 1.10-0.96(m, 5H), 0.88-0.81(m, 21H), 0.03-(0.02)(m, 12H).

[0096] The physicochemical properties of compound 13 are as follows:

[0097] 1) Colorless liquid; Yield: 18%

[0098] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0099] IR cm -1 (KBr): 3096, 1735, 1556, 1368, 1140; 1HNMR (400MHz, CDCl3) δ: 7.84-7.79 (m, 2H, Ar-H), 7.46-7.38 (m, 4H, Ar-H), 7.33-7.26 (m, 2H, Ar-H), 5.71-5.64 (m, 1H ), 5.36-5.23(m, 1H), 4.71(s, 0.42H), 4.63(s, 0.58H), 4.51-4.41(m, 2H), 4.39-4.26(m, 3H), 3.91-3.84(m, 1H), 3.6 0-3.54(m, 1H), 3.27-3.18(m, 1H), 2.87-2.77(m, 1H), 2.37-2.33(m, 1H), 2.25-2.20(m, 1H), 2.16-2.04(m, 1H), 1.91 -1.70(m, 4H), 1.52-1.42(m, 2H), 1.38-1.29(m, 1H), 1.08-0.96(m, 5H), 0.87-0.80(m, 21H), 0.03-(-0.02)(m, 12H).

[0100] The physicochemical properties of compound 14 are as follows:

[0101] 1) White solid, melting point: 60-61°C; yield: 23%

[0102] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0103] IR cm -1 (KBr): 3077, 1732, 1560, 1256, 1129, 887, 779, 746; 1HNMR (400MHz, CDCl3) δ: 8.00-7.97 (m, 2H, Ar-H), 7.92-7.89 (m, 2H, Ar-H), 7.55-7.51 (m, 2H, Ar-H), 7.40-7.34 (m, 2H, Ar-H), 5.71-5.64 (m, 1H) 5.36-5.23 (m, 1H), 4.71 (s, 0.58H), 4.66 (s, 0.42H), 4.48-4.23 (m, 5H), 3.90-3.84 (m, 1H), 3 .60-3.54(m, 1H), 3.27-3.17(m, 1H), 2.85-2.76(m, 1H), 2.38-2.33(m, 1H), 2.26-2.21(m, 1H), 2.12-2.00(m, 1H), 1.8 9-1.72(m, 4H), 1.57-1.43(m, 2H), 1.37-1.33(m, 1H), 1.07-0.96(m, 5H), 0.88-0.82(m, 21H), 0.03-(-0.02)(m, 12H).

[0104] The physicochemical properties of compound 15 are as follows:

[0105] 1) White solid, melting point: 73-74°C; yield: 43%

[0106] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0107] IR cm -1 (KBr): 3097, 3067, 2856, 1741, 1556, 1259, 1127, 886; 1 HNMR (400MHz, CDCl3) δ: 7.96-7.93 (m, 4H, Ar-H), 7.41-7.37 (m, 4H, Ar-H), 5.69-5.63 (m, 1H), 5. 36-5.23(m, 1H), 4.70-4.64(m, 1H), 4.45-4.22(m, 5H), 3.90-3.84(m, 1H), 3.60-3.55(m, 1H), 3.2 6-3.17(m, 1H), 2.83-2.76(m, 1H), 2.37-2.23(m, 1H), 2.25-2.21(m, 1H), 2.11-1.99(m, 1H), 1.91 -1.73(m, 4H), 1.63-1.41(m, 3H), 1.04-0.97(m, 5H), 0.87-0.81(m, 21H), 0.03-(-0.01)(m, 12H).

[0108] The physicochemical properties of compound 16 are as follows:

[0109] 1) Yellow liquid; Yield: 19%

[0110] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0111] IR cm -1 (KBr): 3096, 1731, 1557, 1371, 1274; 1 HNMR (500MHz, CDCl3) δ: 7.81-7.76 (m, 2H, Ar-H), 7.66-7.63 (m, 2H, Ar-H), 7.37-7.29 (m, 4H, Ar-H), 5.71-5.65 ( m, 1H), 5.35-5.24 (m, 1H), 4.71 (s, 0.38H), 4.63 (s, 0.62H), 4.50-4.41 (m, 2H), 4.39-4.27 (m, 3H), 3.91-3.84 (m , 1H), 3.60-3.55(m, 1H), 3.27-3.18(m, 1H), 2.88-2.80(m, 1H), 2.37-2.33(m, 1H), 2.25-2.20(m, 1H), 2.16-2.0 5(m, 1H), 1.92-1.71(m, 4H), 1.56-1.32(m, 3H), 1.04-0.96(m, 5H), 0.87-0.84(m, 21H), 0.03-(-0.02)(m, 12H).

[0112] The physicochemical properties of compound 17 are as follows:

[0113] 1) Yellow liquid; Yield: 24%

[0114] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0115] IR cm -1 (KBr): 3081, 2959, 1725, 1581, 1270, 843; 1HNMR (400MHz, CDCl3) δ: 7.89-7.85 (m, 4H, Ar-H), 7.58-7.54 (m, 4H, Ar-H), 5.69-5.62 (m, 1H), 5.35-5.23 (m, 1H), 4.70 (s, 0.48H), 4.63 (s, 0.52H), 4.48-4.39 (m, 2H), 4.37-4.22 (m, 3H), 3.90-3.84 (m, 1H), 3.59- 3.55(m, 1H), 3.26-3.17(m, 1H), 2.83-2.74(m, 1H), 2.37-2.33(m, 1H), 2.25-2.20(m, 1H), 2.10-1.99(m, 1 H), 1.90-1.69(m, 4H), 1.53-1.31(m, 3H), 1.13-0.96(m, 5H), 0.88-0.81(m, 21H), 0.03-(-0.02)(m, 12H).

[0116] The physicochemical properties of compound 18 are as follows:

[0117] 1) Yellow liquid; Yield: 5%

[0118] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0119] IR cm -1 (KBr): 3087, 2234, 1731, 1557, 1372; 1 HNMR (600MHz, CDCl3) δ: 8.32-8.25 (m, 4H, Ar-H), 7.86-7.82 (m, 2H, Ar-H), 7.61-7.55 (m, 2H, Ar-H), 5.7 1-5.65(m, 1H), 5.35-5.24(m, 1H), 4.70-4.65(m, 1H), 4.52-4.25(m, 5H), 3.90-3.83(m, 1H), 3.59-3.54 (m, 1H), 3.27-3.17 (m, 1H), 2.86-2.73 (m, 1H), 2.37-2.34 (m, 1H), 2.27-2.21 (m, 1H), 2.12-2.05 (m, 1H) , 1.87-1.77(m, 4H), 1.51-1.32(m, 3H), 1.12-0.96(m, 5H), 0.91-0.82(m, 21H), 0.09-(-0.02)(m, 12H).

[0120] The physicochemical properties of compound 19 are as follows:

[0121] 1) Colorless liquid; Yield: 18%

[0122] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0123] IR cm -1 (KBr): 3095, 2961, 2267, 1726, 1558, 1369, 1273; 1 HNMR (400MHz, CDCl3) δ: 8.13-8.09 (m, 4H, Ar-H), 7.76-7.71 (m, 4H, Ar-H), 5.69-5.63 (m, 1H), 5.34- 5.23(m, 1H), 4.69(s, 0.53H), 4.60(s, 0.47H), 4.51-4.26(m, 5H), 3.91-3.82(m, 1H), 3.59-3.54(m, 1 H), 3.26-3.16(m, 1H), 2.84-2.80(m, 1H), 2.37-2.32(m, 1H), 2.26-2.20(m, 1H), 2.11-2.01(m, 1H), 1 .91-1.68(m, 4H), 1.46-1.30(m, 3H), 1.10-0.96(m, 5H), 0.87-0.80(m, 21H), 0.03-(-0.02)(m, 12H).

[0124] The physicochemical properties of compound 20 are as follows:

[0125] 1) Yellow solid, melting point: 101-102°C; yield: 32%

[0126] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0127] IR cm -1 (KBr): 3097, 2846, 1735, 1553, 1363, 1126; 1HNMR (400MHz, CDCl3) δ: 7.95-7.86 (m, 2H, Ar-H), 7.80-7.72 (m, 2H, Ar-H), 7.69-7.59 (m, 4H, Ar-H), 5.70-5.63 ( m, 1H), 5.26-5.15 (m, 1H), 4.69 (s, 0.48H), 4.59 (s, 0.52H), 4.47-4.22 (m, 5H), 3.92-3.84 (m, 1H), 3.60-3.55 (m , 1H), 3.28-3.20(m, 1H), 2.72-2.63(m, 1H), 2.36-2.32(m, 1H), 2.23-2.18(m, 1H), 2.03-1.94(m, 1H), 1.93-1.8 3(m, 1H), 1.78-1.63(m, 3H), 1.57-1.28(m, 3H), 1.14-0.97(m, 5H), 0.87-0.80(m, 21H), 0.03-(-0.02)(m, 12H).

[0128] The physicochemical properties of compound 21 are as follows:

[0129] 1) White solid, melting point: 109-110°C; yield: 28%

[0130] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0131] IR cm -1 (KBr): 3095, 1735, 1543, 1363, 1259, 1127; 1 HNMR (400MHz, CDCl3) δ: 8.85-8.82 (m, 2H, Ar-H), 8.44-8.34 (m, 4H, Ar-H), 7.69-7.62 (m, 2H, Ar-H), 5. 73-5.67(m, 1H), 5.37-5.25(m, 1H), 4.69(s, 0.48H), 4.59(s, 0.52H), 4.55-4.29(m, 5H), 3.90-3.81(m , 1H), 3.59-3.52(m, 1H), 3.27-3.17(m, 1H), 2.88-2.80(m, 1H), 2.35-2.21(m, 2H), 2.13-2.09(m, 1H), 1.89-1.68(m, 4H), 1.52-1.29(m, 3H), 1.13-0.95(m, 5H), 0.91-0.81(m, 21H), 0.03-(-0.05)(m, 12H).

[0132] The physicochemical properties of compound 22 are as follows:

[0133] 1) White solid, melting point: 141-142°C; yield: 37%

[0134] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0135] IR cm -1 (KBr): 3094, 3061, 1735, 1555, 1365, 1128; 1 HNMR (400MHz, CDCl3) δ: 8.29-8.16 (m, 8H, Ar-H), 5.72-5.65 (m, 1H), 5.37-5.25 (m, 1H), 4.70(s, 1H), 4.62(s, 1H), 4.55-4.30(m, 5H), 3.89-3.82(m, 1H), 3.59-3.54(m, 1H), 3.2 6-3.17(m, 1H), 2.87-2.79(m, 1H), 2.37-2.22(m, 2H), 2.12-2.05(m, 1H), 1.86-1.73(m, 4H), 1.61-1.38(m, 3H), 1.01-0.96(m, 5H), 0.87-0.81(m, 21H), 0.03-(-0.04)(m, 12H).

[0136] The physicochemical properties of compound 23 are as follows:

[0137] 1) Colorless liquid; Yield: 16%

[0138] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0139] IR cm -1 (KBr): 2945, 2860, 1736, 1634, 1365, 1258, 1091; 1HNMR (400MHz, CDCl3) δ: 7.79-7.72 (m, 4H, Ar-H), 7.63-7.57 (m, 4H, Ar-H), 5.69-5.61 (m, 1H), 5.31- 5.19(m, 1H), 4.70(s, 0.53H), 4.60(s, 0.47H), 4.49-4.23(m, 5H), 3.91-3.83(m, 1H), 3.60-3.54(m, 1 H), 3.28-3.18(m, 1H), 2.79-2.75(m, 1H), 2.37-2.33(m, 1H), 2.24-2.18(m, 1H), 2.11-2.00(m, 1H), 1 .93-1.70(m, 5H), 1.53-1.41(m, 2H), 1.00-0.96(m, 5H), 0.88-0.78(m, 21H), 0.03-(-0.02)(m, 12H).

[0140] The physicochemical properties of compound 24 are as follows:

[0141] 1) Colorless liquid; Yield: 16%

[0142] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0143] IR cm -1 (KBr): 3086, 2950, ​​2859, 1729, 1632, 1381, 1253, 1091; 1 HNMR (400MHz, CDCl3) δ: 8.29-8.19 (m, 4H, Ar-H), 7.82-7.80 (m, 2H, Ar-H), 7.60-7.51 (m, 2H, Ar-H), 5.72- 5.65 (m, 1H), 5.37-5.24 (m, 1H), 4.70 (s, 0.5H), 4.62 (s, 0.5H), 4.53-4.26 (m, 5H), 3.90-3.83 (m, 1H), 3.59 -3.53(m, 1H), 3.26-3.16(m, 1H), 2.88-2.79(m, 1H), 2.36-2.33(m, 1H), 2.27-2.20(m, 1H), 2.14-1.98(m, 1H), 1.91-1.72(m, 4H), 1.54-1.37(m, 3H), 1.04-0.94(m, 5H), 0.87-0.80(m, 21H), 0.02-(-0.04)(m, 12H).

[0144] The physicochemical properties of compound 25 are as follows:

[0145] 1) Colorless liquid; Yield: 18%

[0146] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0147] IR cm -1 (KBr): 3067, 2948, 2858, 1729, 1633, 1253, 1090; 1 HNMR (400MHz, CDCl3) δ: 8.14-8.10 (m, 4H, Ar-H), 7.71-7.66 (m, 4H, Ar-H), 5.71-5.65 (m, 1H), 5.37- 5.25(m, 1H), 4.71(s, 0.53H), 4.62(s, 0.47H), 4.54-4.27(m, 5H), 3.90-3.83(m, 1H), 3.59-3.54(m, 1 H), 3.26-3.17(m, 1H), 2.87-2.77(m, 1H), 2.37-2.34(m, 1H), 2.26-2.21(m, 1H), 2.14-2.00(m, 1H), 1 .91-1.69(m, 4H), 1.55-1.31(m, 3H), 1.04-0.94(m, 5H), 0.87-0.80(m, 21H), 0.03-(-0.02)(m, 12H).

[0148] The physicochemical properties of compound 26 are as follows:

[0149] 1) Colorless liquid; Yield: 26%

[0150] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0151] IR cm -1 (KBr): 3093, 1726, 1557, 1369, 1256, 1134; 1HNMR (400MHz, CDCl3) δ: 7.92-7.89 (m, 2H, Ar-H), 7.41-7.36 (m, 2H, Ar-H), 7.26-7.19 (m, 4H, Ar-H), 5.70-5.63 (m, 1H ), 5.38-5.25(m, 1H), 4.71(s, 0.45H), 4.64(s, 0.55H), 4.47-4.39(m, 2H), 4.35-4.21(m, 3H), 3.91-3.84(m, 1H), 3.6 0-3.55(m, 1H), 3.27-3.18(m, 1H), 2.84-2.75(m, 1H), 2.60-2.58(m, 6H), 2.38-2.34(m, 1H), 2.26-2.21(m, 1H), 2.14 -2.03(m, 1H), 1.94-1.72(m, 4H), 1.50-1.33(m, 3H), 1.11-0.97(m, 5H), 0.87-0.80(m, 21H), 0.03-(-0.01)(m, 12H).

[0152] The physicochemical properties of compound 27 are as follows:

[0153] 1) Colorless liquid; Yield: 21%

[0154] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0155] IR cm -1 (KBr): 3067, 2958, 2857, 1721, 1556, 1368; 1 HNMR (400MHz, CDCl3) δ: 7.85-7.81 (m, 4H, Ar-H), 7.37-7.28 (m, 4H, Ar-H), 5.71-5.65 (m, 1H), 5.38-5.25 (m, 1H), 4.72 (s, 0.48H), 4.65 (s, 0.52H), 4.49-4.41 (m, 2H), 4.38-4.22 (m, 3H), 3.90-3.84 (m, 1H), 3.60- 3.54(m, 1H), 3.26-3.17(m, 1H), 2.87-2.76(m, 1H), 2.40-2.34(m, 7H), 2.26-2.21(m, 1H), 2.13-2.02(m, 1 H), 1.93-1.71(m, 4H), 1.54-1.35(m, 3H), 1.06-0.96(m, 5H), 0.87-0.82(m, 21H), 0.03-(-0.02)(m, 12H).

[0156] The physicochemical properties of compound 28 are as follows:

[0157] 1) Colorless liquid; Yield: 7%

[0158] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0159] IR cm -1 (KBr): 3065, 2956, 2858, 1724, 1558, 1369, 876; 1 HNMR (400MHz, CDCl3) δ: 7.93-7.90 (m, 4H, Ar-H), 7.26-7.20 (m, 4H, Ar-H), 5.70-5.63 (m, 1H), 5.38-5.24 (m, 1H), 4.70 (s, 0.42H), 4.65 (s, 0.58H), 4.48-4.40 (m, 2H), 4.37-4.21 (m, 3H), 3.90-3.84 (m, 1H), 3.60- 3.54(m, 1H), 3.26-3.17(m, 1H), 2.84-2.75(m, 1H), 2.41-2.33(m, 7H), 2.25-2.20(m, 1H), 2.12-2.00(m, 1 H), 1.93-1.69(m, 4H), 1.58-1.42(m, 3H), 1.06-0.96(m, 5H), 0.88-0.81(m, 21H), 0.03-(-0.02)(m, 12H).

[0160] The physicochemical properties of compound 29 are as follows:

[0161] 1) Colorless liquid; Yield: 28%

[0162] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0163] IR cm -1 (KBr): 3086, 2955, 2853, 1722, 1553, 1364; 1HNMR (400MHz, CDCl3) δ: 7.64-7.60 (m, 2H, Ar-H), 7.56-7.53 (m, 2H, Ar-H), 7.36-7.30 (m, 2H, Ar-H), 7.11-7.07 (m, 2H , Ar-H), 5.70-5.64(m, 1H), 5.38-5.25(m, 1H), 4.71(s, 0.5H), 4.64(s, 0.5H), 4.47-4.42(m, 2H), 4.38-4.21(m, 3H), 3 .90-3.83(m, 7H), 3.60-3.54(m, 1H), 3.26-3.17(m, 1H), 2.88-2.74(m, 1H), 2.37-2.33(m, 1H), 2.26-2.20(m, 1H), 2.1 3-2.02(m, 1H), 1.88-1.74(m, 4H), 1.50-1.35(m, 3H), 1.10-0.96(m, 5H), 0.88-0.81(m, 21H), 0.03-(-0.02)(m, 12H).

[0164] The physicochemical properties of compound 30 are as follows:

[0165] 1) Colorless liquid; Yield: 18%

[0166] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0167] IR cm -1 (KBr): 3094, 2961, 1720, 1558, 1475, 1369, 1256, 888; 1 HNMR (400MHz, CDCl3) δ: 8.00-7.95 (m, 4H, Ar-H), 6.92-6.88 (m, 4H, Ar-H), 5.69-5.62 (m, 1H), 5.37-5.25 (m, 1H), 4.71 (s, 0.45H), 4.65 (s, 0.55H), 4.47-4.38 (m, 2H), 4.35-4.19 (m, 3H), 3.90-3.81 (m, 7H), 3.59- 3.55(m, 1H), 3.26-3.18(m, 1H), 2.81-2.75(m, 1H), 2.38-2.33(m, 1H), 2.25-2.20(m, 1H), 2.11-2.00(m, 1 H), 1.92-1.69(m, 4H), 1.53-1.37(m, 3H), 1.13-0.96(m, 5H), 0.87-0.81(m, 21H), 0.03-(-0.02)(m, 12H).

[0168] The physicochemical properties of compound 31 are as follows:

[0169] 1) Colorless liquid; Yield: 15%

[0170] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0171] IR cm -1 (KBr): 3093, 1729, 1722, 1557, 1371, 1156; 1 HNMR (400MHz, CDCl3) δ: 7.65-7.61 (m, 2H, Ar-H), 7.46-7.44 (m, 2H, Ar-H), 6.84-6.80 (m, 2H, Ar-H), 6.03-6.02 (m, 4H ), 5.69-5.62(m, 1H), 5.36-5.23(m, 1H), 4.70(s, 0.42H), 4.66(s, 0.58H), 4.46-4.36(m, 2H), 4.33-4.19(m, 3H), 3.9 1-3.85 (m, 1H), 3.60-3.55 (m, 1H), 3.27-3.19 (m, 1H), 2.82-2.74 (m, 1H), 2.38-2.33 (m, 1H), 2.25-2.20 (m, 1H), 2.09 -1.97(m, 1H), 1.93-1.67(m, 4H), 1.53-1.38(m, 3H), 1.13-0.97(m, 5H), 0.87-0.82(m, 21H), 0.03-(-0.02)(m, 12H).

[0172] The physicochemical properties of compound 32 are as follows:

[0173] 1) Colorless liquid; Yield: 17%

[0174] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0175] IR cm -1 (KBr): 3077, 2939, 2859, 1739, 1639, 1464, 1367, 1097; 1HNMR (600MHz, CDCl3) δ: 7.56-7.52 (m, 4H, Ar-H), 6.88-6.85 (m, 2H, Ar-H), 5.67-5.62 (m, 1H), 5.35-5. 23(m, 1H), 4.70-4.66(m, 1H), 4.46-4.17(m, 13H), 3.90-3.86(m, 1H), 3.59-3.56(m, 1H), 3.25-3.19(m , 1H), 2.80-2.74(m, 1H), 2.36-2.33(m, 1H), 2.24-2.20(m, 1H), 2.07-1.98(m, 1H), 1.91-1.84(m, 1H), 1.81-1.68(m, 3H), 1.63-1.41(m, 3H), 1.07-0.96(m, 5H), 0.91-0.81(m, 21H), 0.03-(-0.02)(m, 12H).

[0176] The physicochemical properties of compound 33 are as follows:

[0177] 1) Colorless liquid; Yield: 17%

[0178] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0179] IR cm -1 (KBr): 3081, 2952, 2864, 1726, 1628, 1496, 1257, 1089; 1 HNMR (500MHz, CDCl3) δ: 7.51-7.47 (m, 2H, Ar-H), 7.17-7.14 (m, 2H, Ar-H), 6.91-6.88 (m, 2H), 5.69-5.64 (m, 1 H), 5.35-5.24(m, 1H), 4.70(s, 0.51H), 4.65(s, 0.49H), 4.51-4.39(m, 2H), 4.35-4.23(m, 3H), 3.90-3.85(m, 7 H), 3.60-3.55(m, 1H), 3.27-3.19(m, 1H), 2.85-2.76(m, 1H), 2.37-2.33(m, 1H), 2.25-2.20(m, 1H), 2.10-2.01 (m, 1H), 1.91-1.69 (m, 4H), 1.57-1.36 (m, 3H), 1.03-0.94 (m, 5H), 0.87-0.81 (m, 21H), 0.03-(-0.02) (m, 12H).

[0180] The physicochemical properties of compound 34 are as follows:

[0181] 1) Colorless liquid; Yield: 21%

[0182] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0183] IR cm -1 (KBr): 3040, 2943, 2857, 1720, 1383, 1248, 1092; 1 HNMR (500MHz, CDCl3) δ: 7,65-7.63 (m, 4H, Ar-H), 7.18-7.17 (m, 2H, Ar-H), 5.71-5.66 (m, 1H), 5.38-5.26 (m, 1 H), 4.72 (s, 0.5H), 4.67 (s, 0.5H), 4.50-4.48 (m, 1H), 4.46-4.39 (m, 1H), 4.37-4.20 (m, 3H), 3.90-3.84 (m, 1H) , 3.60-3.55(m, 1H), 3.26-3.17(m, 1H), 2.85-2.76(m, 1H), 2.37-2.34(m, 13H), 2.26-2.21(m, 1H), 2.11-1.99 (m, 1H), 1.92-1.72 (m, 4H), 1.54-1.39 (m, 3H), 1.04-0.96 (m, 5H), 0.87-0.82 (m, 21H), 0.03-(-0.03) (m, 12H).

[0184] The physicochemical properties of compound 35 are as follows:

[0185] 1) Colorless liquid; Yield: 14%

[0186] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0187] IR cm -1 (KBr): 3065, 2956, 2856, 1724, 1558, 1369, 1272; 1HNMR (400MHz, CDCl3) δ: 7.33-7.26 (m, 10H, Ar-H), 5.51-5.44 (m, 1H), 5.14-5.06 (m, 1H), 4.73 -4.69(m, 1H), 4.46(s, 0.64H), 4.37(s, 0.36H), 4.17-4.11(m, 1H), 4.07-3.90(m, 4H), 3.62-3 .59(m, 5H), 3.29-3.24(m, 1H), 2.48-2.36(m, 2H), 2.19-2.15(m, 1H), 1.94-1.85(m, 1H), 1.80 -1.60(m, 4H), 1.57-1.43(m, 3H), 1.06-1.00(m, 5H), 0.88-0.82(m, 21H), 0.05-0.00(m, 12H).

[0188] The physicochemical properties of compound 36 are as follows:

[0189] 1) Colorless liquid; Yield: 28%

[0190] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0191] IR cm -1 (KBr): 3096, 1735, 1556, 1373, 1173; 1 HNMR (400MHz, CDCl3) δ: 7.70-7.65 (m, 2H), 7.54-7.49 (m, 4H, Ar-H), 7.39-7.36 (m, 6H, Ar-H), 6.47-6.39 (m, 2H), 5. 69-5.62 (m, 1H), 5.31-5.20 (m, 1H), 4.74-4.71 (m, 1H), 4.52-4.50 (m, 1H), 4.36-4.28 (m, 1H), 4.27-4.11 (m, 3H), 3.9 1-3.85(m, 1H), 3.60-3.54(m, 1H), 3.28-3.21(m, 1H), 2.75-2.67(m, 1H), 2.39-2.34(m, 1H), 2.26-2.22(m, 1H), 2.01 -1.86(m, 2H), 1.79-1.65(m, 3H), 1.54-1.41(m, 3H), 1.12-0.97(m, 5H), 0.91-0.82(m, 21H), 0.09-(-0.09)(m, 12H).

[0192] The physicochemical properties of compound 37 are as follows:

[0193] 1) Colorless liquid; Yield: 22%

[0194] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0195] IR cm -1 (KBr): 3122, 1737, 1608, 1400, 1164; 1 HNMR (400MHz, CDCl3) δ: 7.66-7.60 (m, 2H), 7.52-7.47 (m, 4H, Ar-H), 7.09-7.04 (m, 4H, Ar-H), 6.38-6.31 (m, 2H ), 5.68-5.62(m, 1H), 5.31-5.19(m, 1H), 4.74-4.70(m, 1H), 4.51-4.49(m, 1H), 4.35-4.28(m, 1H), 4.26-4.10(m , 3H), 3.91-3.85(m, 1H), 3.60-3.55(m, 1H), 3.28-3.21(m, 1H), 2.71-2.65(m, 1H), 2.39-2.34(m, 1H), 2.26-2.2 2(m, 1H), 2.00-1.86(m, 2H), 1.79-1.45(m, 6H), 1.16-0.97(m, 5H), 0.86-0.83(m, 21H), 0.02-(-0.09)(m, 12H).

[0196] The physicochemical properties of compound 38 are as follows:

[0197] 1) White solid, melting point: 97-98°C; yield: 27%

[0198] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0199] IR cm -1 (KBr): 3123, 2859, 1732, 1607, 1575, 1400, 1265, 1165; 1HNMR (500MHz, CDCl3) δ: 7.63-7.58 (m, 2H), 7.44-7.41 (m, 4H, Ar-H), 7.35-7.33 (m, 4H, Ar-H), 6.42-6.36 (m, 2H), 5 .67-5.62(m, 1H), 5.30-5.20(m, 1H), 4.74(s, 0.4H), 4.70(s, 0.6H), 4.51-4.49(m, 1H), 4.35-4.29(m, 1H), 4.26-4 .11(m,3H),3.91-3.85(m,1H),3.60-3.55(m,1H),3.28-3.21(m,1H),2.72-2.69(m,1H),2.39-2.35(m,1H),2.26- 2.22(m, 1H), 1.99-1.85(m, 2H), 1.79-1.45(m, 6H), 1.15-0.97(m, 5H), 0.87-0.83(m, 21H), 0.02-(-0.09)(m, 12H).

[0200] The physicochemical properties of compound 39 are as follows:

[0201] 1) Colorless liquid; Yield: 21%

[0202] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0203] IR cm -1 (KBr): 3124, 2849, 1732, 1641, 1470, 1400, 1265; 1 HNMR (400MHz, CDCl3) δ: 7.62-7.56 (m, 2H), 7.52-7.49 (m, 4H, Ar-H), 7.38-7.34 (m, 4H, Ar-H), 6.44-6.37 (m, 2H), 5. 67-5.61 (m, 1H), 5.30-5.18 (m, 1H), 4.73-4.69 (m, 1H), 4.50-4.48 (m, 1H), 4.35-4.28 (m, 1H), 4.25-4.09 (m, 3H), 3.9 1-3.85 (m, 1H), 3.60-3.54 (m, 1H), 3.27-3.20 (m, 1H), 2.74-2.66 (m, 1H), 2.39-2.35 (m, 1H), 2.26-2.21 (m, 1H), 1.98 -1.85(m, 2H), 1.79-1.66(m, 3H), 1.58-1.45(m, 3H), 1.16-0.97(m, 5H), 0.86-0.80(m, 21H), 0.02-(-0.09)(m, 12H).

[0204] The physicochemical properties of compound 40 are as follows:

[0205] 1) Yellow liquid; Yield: 17%

[0206] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0207] IR cm -1 (KBr): 3117, 1725, 1557, 1401, 1354, 879; 1 HNMR (400MHz, CDCl3) δ: 8.26-8.23 (m, 4H), 7.73-7.63 (m, 6H), 6.58-6.51 (m, 2H), 5.69-5.62 (m, 1H), 5.30-5 .20(m, 1H), 4.74-4.69(m, 1H), 4.49-4.48(m, 1H), 4.38-4.32(m, 1H), 4.31-4.09(m, 3H), 3.91-3.84(m, 1H), 3.60-3.54(m, 1H), 3.28-3.21(m, 1H), 2.77-2.67(m, 1H), 2.39-2.35(m, 1H), 2.27-2.19(m, 1H), 2.01-1.86( m, 2H), 1.79-1.69 (m, 3H), 1.56-1.46 (m, 3H), 1.06-0.97 (m, 5H), 0.86-0.82 (m, 21H), 0.02-(-0.10) (m, 12H).

[0208] The physicochemical properties of compound 41 are as follows:

[0209] 1) Yellow liquid; Yield: 22%

[0210] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0211] IR cm -1 (KBr): 3096, 3063, 2967, 1736, 1545, 1274, 1101; 1 HNMR (400 MHz, CDCl 3)δ: 7.71-7.58 (m, 10H), 6.53-6.46 (m, 2H), 5.69-5.63 (m, 1H), 5.31-5.20 (m, 1H), 4.74-4.69 (m, 1H) , 4.51-4.49(m, 1H), 4.38-4.30(m, 1H), 4.28-4.12(m, 3H), 3.91-3.84(m, 1H), 3.60-3.54(m, 1H), 3 .28-3.20(m,1H),2.77-2.64(m,1H),2.39-2.35(m,1H),2.27-2.22(m,1H),2.03-1.86(m,2H),1.7 9-1.61(m, 4H), 1.56-1.44(m, 2H), 1.08-0.97(m, 5H), 0.87-0.82(m, 21H), 0.02-(-0.12)(m, 12H).

[0212] The physicochemical properties of compound 42 are as follows:

[0213] 1) Colorless liquid; Yield: 22%

[0214] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0215] IR cm -1 (KBr): 3124, 2850, 1714, 1591, 1399, 1354, 1165; 1 HNMR (400MHz, CDCl3) δ: 7.68-7.62 (m, 2H), 7.43-7.39 (m, 4H, Ar-H), 7.19-7.16 (m, 4H, Ar-H), 6.42-6.34 (m, 2H), 5. 68-5.62 (m, 1H), 5.31-5.20 (m, 1H), 4.74-4.70 (m, 1H), 4.53-4.51 (m, 1H), 4.35-4.29 (m, 1H), 4.26-4.19 (m, 3H), 3.9 2-3.86(m, 1H), 3.61-3.55(m, 1H), 3.28-3.21(m, 1H), 2.75-2.67(m, 1H), 2.39-2.34(m, 7H), 2.26-2.22(m, 1H), 2.00 -1.86(m, 2H), 1.80-1.65(m, 3H), 1.60-1.45(m, 3H), 1.13-0.97(m, 5H), 0.87-0.83(m, 21H), 0.03-(-0.09)(m, 12H).

[0216] The physicochemical properties of compound 43 are as follows:

[0217] 1) Colorless liquid; Yield: 19%

[0218] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0219] IR cm -1 (KBr): 3117, 1725, 1528, 1472, 1401, 1255, 879; 1 HNMR (400MHz, CDCl3) δ: 7.65-7.61(m, 2H), 7.48-7.44(m, 4H), 6.90-6.87(m, 4H), 6.32-6.26(m, 2H), 5.67-5.63( m, 1H), 5.30-5.21 (m, 1H), 4.74-4.71 (m, 1H), 4.53-4.50 (m, 1H), 4.33-4.28 (m, 1H), 4.24-4.07 (m, 3H), 3.91-3.8 6(m, 1H), 3.83-3.81(m, 6H), 3.60-3.56(m, 1H), 3.27-3.22(m, 1H), 2.74-2.67(m, 1H), 2.39-2.35(m, 1H), 2.26-2 .22(m, 1H), 2.02-1.86(m, 2H), 1.79-1.46(m, 6H), 1.15-0.97(m, 5H), 0.87-0.84(m, 21H), 0.03-(-0.08)(m, 12H).

[0220] The physicochemical properties of compound 44 are as follows:

[0221] 1) Yellow liquid; Yield: 26%

[0222] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0223] IR cm -1 (KBr): 3116, 1736, 1557, 1402, 1164, 1HNMR (400MHz, CDCl3) δ: 7.58-7.52 (m, 2H), 7.05-6.99 (m, 4H, Ar-H), 6.86-6.82 (m, 2H, Ar-H), 6.30-6.22 (m, 2H) , 5.67-5.60(m, 1H), 5.30-5.18(m, 1H), 4.73-4.70(m, 1H), 4.51-4.49(m, 1H), 4.33-4.07(m, 12H), 3.92-3.86(m , 1H), 3.60-3.55(m, 1H), 3.27-3.21(m, 1H), 2.70-2.62(m, 1H), 2.39-2.34(m, 1H), 2.25-2.21(m, 1H), 2.01-1.8 8(m, 2H), 1.77-1.65(m, 3H), 1.57-1.47(m, 3H), 1.06-0.97(m, 5H), 0.86-0.83(m, 21H), 0.02-(-0.08)(m, 12H).

[0224] The physicochemical properties of compound 45 are as follows:

[0225] 1) Colorless liquid; Yield: 14%

[0226] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0227] IR cm -1 (KBr): 3123, 2853, 1716, 1604, 1400, 1258; 1 HNMR (600MHz, CDCl3) δ: 8.78-8.76 (m, 4H, Ar-H), 7.83-7.80 (m, 4H, Ar-H), 5.69-5.65 (m, 1H), 5.33-5.24 (m, 1H), 4.69 (s, 0.44H), 4.62 (s, 0.56H), 4.52-4.28 (m, 5H), 3.88-3.83 (m, 1H), 3.58-3.54 (m, 1H), 3.25- 3.18(m, 1H), 2.84-2.77(m, 1H), 2.36-2.33(m, 1H), 2.25-2.20(m, 1H), 2.11-2.03(m, 1H), 1.89-1.71(m, 4 H), 1.59-1.52(m, 1H), 1.44-1.40(m, 2H), 1.03-0.96(m, 5H), 0.86-0.80(m, 21H), 0.02-(-0.03)(m, 12H).

[0228] The physicochemical properties of compound 46 are as follows:

[0229] 1) White solid, melting point: 83-84°C; yield: 20%

[0230] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0231] IR cm -1 (KBr): 3128, 2954, 2849, 1733, 1559, 1124; 1 HNMR (400MHz, CDCl3) δ: 9.23-9.20 (m, 2H, Ar-H), 8.79-8.76 (m, 2H, Ar-H), 8.32-8.27 (m, 2H, Ar-H), 7.43-7.37 (m, 2H, Ar-H), 5.71-5.65(m, 1H), 5.36-5.24(m, 1H), 4.69(s, 0.46H), 4.62(s, 0.54H), 4.54-4.46(m, 1H), 4.43-4.26(m, 4H), 3.89-3.83(m, 1H), 3.59-3.54(m, 1H), 3.26-3.17(m, 1H), 2.84-2.77(m, 1H), 2.36-2.32(m, 1H), 2.26-2.20(m, 1H), 2. 14-2.03(m, 1H), 1.97-1.75(m, 5H), 1.60-1.40(m, 2H), 1.17-0.96(m, 5H), 0.87-0.81(m, 21H), 0.03-(-0.03)(m, 12H).

[0232] The physicochemical properties of compound 47 are as follows:

[0233] 1) White solid, melting point: 80-81°C; yield: 25%

[0234] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0235] IR cm -1 (KBr): 3122, 12851, 1736, 1608, 1400; 1HNMR (400MHz, CDCl3) δ: 8.40-8.34 (m, 4H, Ar-H), 7.32-7.26 (m, 2H, Ar-H), 5.72-5.66 (m, 1H), 5.36-5.24 (m, 1H), 4.67 (s, 0.42H), 4.61 (s, 0.58H), 4.54-4.46 (m, 1H), 4.42-4.25 (m, 4H), 3.90-3.84 (m, 1H), 3.59- 3.54(m, 1H), 3.26-3.18(m, 1H), 2.88-2.78(m, 1H), 2.36-2.31(m, 1H), 2.25-2.19(m, 1H), 2.14-2.03(m, 1 H), 1.91-1.71(m, 4H), 1.60-1.38(m, 3H), 1.10-0.96(m, 5H), 0.87-0.81(m, 21H), 0.02-(-0.03)(m, 12H).

[0236] The physicochemical properties of compound 48 are as follows:

[0237] 1) Yellow liquid; Yield: 21%

[0238] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0239] IR cm -1 (KBr): 3117, 2859, 1736, 1572, 1471, 1258; 1 HNMR (600MHz, CDCl3) δ: 8.52-8.49 (m, 2H, Ar-H), 8.17-8.13 (m, 2H, Ar-H), 7.34-7.29 (m, 2H, Ar-H), 5.70-5.66 ( m, 1H), 5.33-5.23 (m, 1H), 4.70 (s, 0.44H), 4.62 (s, 0.56H), 4.52-4.43 (m, 1H), 4.40-4.28 (m, 4H), 3.89-3.84 (m , 1H), 3.59-3.54(m, 1H), 3.26-3.18(m, 1H), 2.86-2.79(m, 1H), 2.36-2.33(m, 1H), 2.25-2.20(m, 1H), 2.14-2.0 6(m, 1H), 1.90-1.54(m, 6H), 1.46-1.42(m, 1H), 1.04-0.96(m, 5H), 0.87-0.81(m, 21H), 0.02-(-0.03)(m, 12H).

[0240] The physicochemical properties of compound 49 are as follows:

[0241] 1) Colorless liquid; Yield: 16%

[0242] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0243] IR cm -1 (KBr): 3120, 1735, 1559, 1401; 1 HNMR (400MHz, CDCl3) δ: 8.49-8.46 (m, 2H, Ar-H), 8.09-8.04 (m, 2H, Ar-H), 7.37-7.31 (m, 2H, Ar-H), 5. 72-5.66(m, 1H), 5.34-5.23(m, 1H), 4.71(s, 0.55H), 4.62(s, 0.45H), 4.53-4.28(m, 5H), 3.90-3.84(m , 1H), 3.60-3.54(m, 1H), 3.27-3.18(m, 1H), 2.87-2.80(m, 1H), 2.37-2.33(m, 1H), 2.26-2.19(m, 1H), 2.14-1.75(m, 5H), 1.57-1.40(m, 3H), 1.04-0.96(m, 5H), 0.86-0.81(m, 21H), 0.03-(-0.02)(m, 12H).

[0244] The physicochemical properties of compound 50 are as follows:

[0245] 1) Colorless liquid; Yield: 21%

[0246] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0247] IR cm -1 (KBr): 3093, 2906, 1737, 1556, 1128; 1HNMR (600MHz, CDCl3) δ: 8.30-8.28 (m, 2H, Ar-H), 8.14-8.11 (m, 2H, Ar-H), 6.93-6.89 (m, 2H, Ar-H), 5.68-5.64 (m, 1H), 5.34-5.24(m, 1H), 4.69-4.68(m, 0.4H), 4.62-4.61(m, 0.6H), 4.47-4.40(m, 2H), 4.33-4.21(m, 3H), 4.03-4.01(m, 6H) , 3.89-3.84(m, 1H), 3.58-3.54(m, 1H), 3.25-3.17(m, 1H), 2.85-2.77(m, 1H), 2.36-2.33(m, 1H), 2.23-2.19(m, 1H), 2. 09-2.02(m, 1H), 1.90-1.69(m, 5H), 1.58-1.41(m, 2H), 1.03-0.96(m, 5H), 0.90-0.80(m, 21H), 0.02-(-0.03)(m, 12H).

[0248] The physicochemical properties of compound 51 are as follows:

[0249] 1) Colorless liquid; Yield: 25%

[0250] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0251] IR cm -1 (KBr): 3121, 2859, 1734, 1400, 1267; 1 HNMR (400MHz, CDCl3) δ: 8.87-8.85 (m, 2H, Ar-H), 8.41-8.34 (m, 2H, Ar-H), 7.02-6.97 (m, 2H, Ar-H), 5.69-5.63 ( m, 1H), 5.34-5.23 (m, 1H), 4.68 (s, 0.46H), 4.62 (s, 0.54H), 4.51-4.43 (m, 1H), 4.41-4.25 (m, 4H), 3.89-3.83 (m , 1H), 3.59-3.54(m, 1H), 3.26-3.17(m, 1H), 2.85-2.74(m, 1H), 2.36-2.32(m, 1H), 2.25-2.20(m, 1H), 2.11-1.9 9(m, 1H), 1.89-1.71(m, 4H), 1.64-1.41(m, 3H), 1.04-0.96(m, 5H), 0.86-0.81(m, 21H), 0.02-(-0.03)(m, 12H).

[0252] The physicochemical properties of compound 52 are as follows:

[0253] 1) Colorless liquid; Yield: 20%

[0254] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0255] IR cm -1 (KBr): 3123, 2855, 1733, 1606, 1470, 1400; 1 HNMR (400MHz, CDCl3) δ: 8.98-8.95 (m, 2H, Ar-H), 8.24-8.18 (m, 2H, Ar-H), 7.43-7.38 (m, 2H, Ar-H), 5.69-5.63 ( m, 1H), 5.33-5.22 (m, 1H), 4.68 (s, 0.45H), 4.62 (s, 0.55H), 4.51-4.43 (m, 1H), 4.41-4.25 (m, 4H), 3.89-3.83 (m , 1H), 3.59-3.54(m, 1H), 3.26-3.17(m, 1H), 2.84-2.73(m, 1H), 2.36-2.32(m, 1H), 2.25-2.20(m, 1H), 2.10-2.0 0(m, 1H), 1.90-1.72(m, 4H), 1.66-1.43(m, 3H), 1.11-0.96(m, 5H), 0.87-0.80(m, 21H), 0.02-(-0.03)(m, 12H).

[0256] The physicochemical properties of compound 53 are as follows:

[0257] 1) White solid, melting point: 94-95°C; yield: 17%

[0258] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0259] IR cm -1 (KBr): 2944, 2858, 1726, 1638, 1450, 1370, 1103; 1HNMR (400MHz, CDCl3) δ: 8.95-8.92 (m, 2H, Ar-H), 8.13-8.06 (m, 2H, Ar-H), 7.60-7.55 (m, 2H, Ar-H), 5.69-5.63 (m, 1H), 5.32-5.22 (m, 1H), 4.68 (s, 0.5H), 4.62 (s, 0.5H), 4.51-4.43 (m, 1H), 4.41-4.25 (m, 4H), 3.90-3.84 (m, 1H), 3.59-3.55(m, 1H), 3.26-3.18(m, 1H), 2.84-2.73(m, 1H), 2.37-2.32(m, 1H), 2.25-2.20(m, 1H), 2.10-2.0 0 (m, 1H), 1.87-1.66 (m, 4H), 1.53-1.41 (m, 3H), 1.11-0.95 (m, 5H), 0.91-0.81 (m, 21H), 0.03-(-0.02) (m, 12H).

[0260] The physicochemical properties of compound 54 are as follows:

[0261] 1) Colorless liquid; Yield: 24%

[0262] 2) Infrared spectrum and H NMR spectrum data of the compound:

[0263] IR cm -1 (KBr): 3123, 2961, 2898, 1729, 1608, 1456, 1398, 1269, 1111; 1 HNMR (400MHz, CDCl3) δ: 8.83-8.81 (m, 2H, Ar-H), 8.14-8.09 (m, 2H, Ar-H), 6.77-6.73 (m, 2H, Ar-H), 5.68-5.62 (m, 1 H), 5.35-5.23 (m, 1H), 4.69 (s, 0.4H), 4.64 (s, 0.6H), 4.48-4.38 (m, 2H), 4.36-4.15 (m, 3H), 3.99-3.98 (m, 6H), 3.90 -3.84(m, 1H), 3.59-3.54(m, 1H), 3.26-3.18(m, 1H), 2.82-2.73(m, 1H), 2.37-2.32(m, 1H), 2.24-2.20(m, 1H), 2.10 -1.99(m, 1H), 1.90-1.69(m, 4H), 1.57-1.41(m, 3H), 1.06-0.96(m, 5H), 0.91-0.81(m, 21H), 0.02-(-0.03)(m, 12H).

[0264] Example 2: Bioassay of the test compound against the oriental armyworm:

[0265] i. Test insects: 3rd instar larvae of the Oriental armyworm (Mythimna separata Walker), subcultured by the Plant Protection Laboratory of Northwest Agriculture and Forestry University.

[0266] ii. Samples and reagents: Toosendanin (purity>78%, provided by the Pollution-free Research Center of Northwest Agriculture and Forestry University) (positive control agent); parent andrographolide (compound a, 98%, purchased from Baoji Fangsheng Biotechnology Co., Ltd.), intermediate (bd) prepared in Example 1 and target compound 1-54. Acetone (solvent, purchased from Chengdu Kelong Chemical Reagent Factory, analytical grade).

[0267] iii. Bioassay method: Leaflet butterfly addition method:

[0268] Acetone was used as a blank control and Toosendanin as a drug control to determine the activity of the test compound at a concentration of 1 mg / mL. A layer of filter paper was laid on the bottom of a 9-cm diameter glass culture dish and water was added to keep it moist. Twelve 3rd-instar early larvae were picked from each dish, and three replicates were set for each treatment sample. Freshly picked oat leaves were removed from the main veins and cut into 1×1 cm 2 The small leaf butterflies were immersed in the pre-prepared test solution and control solution for 3s, and then fed to test insects after natural drying; they were raised under the conditions of room temperature around 25℃, humidity 65%-80%, and light intensity 12h / 12h; after the test insects finished eating the oat leaves, the leaf butterflies with the drug solution were added, and after raising for 48h, they were fed with fresh leaves without the drug solution until they emerged; the food intake, number of survivors, symptoms, etc. of the test insects were recorded regularly; the corrected mortality rate (%) of the test insects at different stages was calculated according to the following formula

[0269]

[0270] Conclusion: The results shown in Table 1 show that at a concentration of 1 mg / mL, compound 22 has good stomach poison activity against the larvae of the oriental armyworm, with a final corrected mortality rate of 59.5%, which is higher than the positive control agent toosendanin (48.9%), and the activity is significantly improved compared with the parent andrographolide (34.0%). It is expected to be used to prepare highly effective botanical insecticides.

[0271] Example 3: Bioassay of the test compound against apple yellow aphid:

[0272] i. Test insects: wingless adult apple aphids (Aphis citricola Van der Goot), collected from the Horticulture Farm of Northwest Agriculture and Forestry University.

[0273] ii. Samples and reagents: methomyl (95.6%, purchased from Shaanxi Shangge Road Biotechnology Co., Ltd.) (positive control agent), parent andrographolide (a), intermediate (bd) prepared in Example 1 and target compound 1-54, acetone.

[0274] iii. Bioassay method: Micro-drop method:

[0275] The test compound was prepared into a solution with a concentration of 1 mg / mL using acetone (the concentration of methomyl was 0.1 mg / mL), and acetone was used as a blank control. 0.04 μL of the test solution was dripped on the abdomen of the selected aphids (uniform size, healthy wingless adult aphids), and then the test insects were transferred to a culture dish with a diameter of 9 cm and a filter paper pad on the bottom for moisture retention. There were 30 insects in each dish, and each culture dish was a replicate. Each treatment was repeated 3 times. Fresh leaves were fed, and the petioles were wrapped with wet absorbent cotton and then covered with gauze (or toilet paper). The insects were raised under the conditions of a light cycle of L:D = 14h:10h, a temperature of (25±1)℃, and a relative humidity of (50±7)%. The death of the test insects was observed and recorded after 24h and 48h, and the death of the aphids was judged as death when the feet and antennae were completely motionless when the brush touched them. The mortality rate (%) and the corrected mortality rate (%) of the test insects at 24h and 48h were calculated according to the following formula.

[0276]

[0277] Conclusion: The results shown in Table 2 indicate that at a dose of 0.04 μg / head, the 48-hour aphidicide activity of some compounds (10, 15, 45, 46) was higher than 50%, which was significantly higher than that of the parent andrographolide. Therefore, they are expected to be used in the preparation of highly efficient, environmentally friendly, and low-toxic botanical aphidicide.

[0278] Example 4: Bioassay of the test compound against Tetranychus cinnabarinus:

[0279] i. Test insects: Female adult cinnabarinus spider mites (Tetranychus cinnabarinus Biosduval), which are a sensitive strain that has been raised in the Plant Protection Laboratory of Northwest Agriculture and Forestry University.

[0280] ii. Samples and reagents: spirodiclofen (98.32%, purchased from Shaanxi Meibang Pesticide Co., Ltd.) (positive control agent), parent andrographolide (a), intermediate (bd) prepared in Example 1 and target compound 1-54, acetone, distilled water and Tween 80.

[0281] iii. Bioassay method: Slide immersion method:

[0282] ① Preparation of 0.1‰ Tween 80 stock solution: weigh 25 mg of Tween 80 and dissolve it in 5 mL of acetone solution, then dilute to 250 mL with distilled water for later use.

[0283] ② Preparation of test solution: Weigh 2-3 mg of the test compound, dissolve it with an appropriate amount of acetone (2% of the target volume), and then prepare it to 0.5 mg / mL with the prepared 0.1‰ Tween 80 solution.

[0284] ③ Preparation of test mites: stick a 1cm wide double-sided tape on one end of the slide, use a No. 0 brush to select healthy and active female adult cinnabarinus mites of the same age, carefully and neatly stick their backs on the double-sided tape, stick about 35 mites to each slide, arrange them in 2 rows, put the slide with the test mites on an iron plate padded with a moist sponge, and put the iron plate in a light incubator under the conditions of 26±1℃, relative humidity 60%~80%, and light L:D=14h:10h. After 4 hours, check with a stereo microscope, remove dead and inactive individuals, and record the number of live mites on each slide.

[0285] ④ Soak in medicine: Dip the end of the glass slide with the mite stuck on it in the test solution for 5 seconds after shaking, then take it out, carefully absorb the excess solution with a small filter paper strip (be careful not to touch the mite body), then put it back on the iron plate, and place it in a light incubator under the same breeding conditions. One glass slide is one treatment, and each treatment is repeated 3 times, with 0.1‰ Tween 80 solution as the blank control.

[0286] ⑤ Result statistics: After 24 hours of immersion treatment, take out the slide and check the results under a stereo microscope. During the inspection, touch the mite body with the tip of a brush. Those whose chelicerae do not move are considered dead, and the number of dead individuals is recorded. Observe and record for 72 hours. Calculate the mortality rate (%) and corrected mortality rate (%) of the test insects according to the following formula.

[0287]

[0288] Conclusion: The results shown in Table 3 show that at a concentration of 0.5 mg / mL, the 72-hour acaricidal activity of compounds 4, 5, and 6 was higher than 60%, which was significantly higher than that of the parent andrographolide. Therefore, they are expected to be used in the preparation of highly efficient, environmentally friendly, and low-toxic botanical acaricides.

[0289] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the embodiments of the present invention. For those skilled in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all the embodiments here. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection scope of the claims of the present invention.

[0290]

[0291]

[0292]

[0293]

Claims

1. An andrographolide diester derivative, characterized in that: The general structural formula of the derivative is shown in Formula I: in: R is selected from alkyl, phenyl, substituted phenyl, benzyl, cinnamyl, substituted cinnamyl, pyridyl or substituted pyridyl.

2. The andrographolide diester derivative according to claim 1, characterized in that: R in the formula I is selected from: (1) R = CH3; (2) R = (CH2)2CH3; (3) R = (CH2)4CH3; (4) R = (CH2)6CH3; (5) R = (CH2)7CH3; (6) R = (CH2) 8CH3; (7) R = (CH2)9CH3; (8)R=(CH2) 10 CH3; (9) R = phenyl; (10) R = 2-fluorophenyl; (11) R = 3-fluorophenyl; (12) R = 4-fluorophenyl; (13) R = 2-chlorophenyl; (14) R = 3-chlorophenyl; (15) R = 4-chlorophenyl; (16) R = 2-bromophenyl; (17) R = 4-bromophenyl; (18) R = 3-cyanophenyl; (19) R = 4-cyanophenyl; (20) R = 2-nitrophenyl; (21) R = 3-nitrophenyl; (22) R = 4-nitrophenyl; (23) R = 2-trifluoromethylphenyl; (24) R = 3-trifluoromethylphenyl; (25) R = 4-trifluoromethylphenyl; (26) R = 2-methylphenyl; (27) R = 3-methylphenyl; (28) R = 4-methylphenyl; (29) R = 3-methoxyphenyl; (30) R = 4-methoxyphenyl; (31) R = 3,4-(methylenedioxy)phenyl; (32) R = 3,4-(ethylenedioxy)phenyl; (33) R = 2-methoxy-5-fluorophenyl; (34) R = 3,5-dimethylphenyl; (35) R = benzyl; (36) R = cinnamyl; (37) R = 4-fluorocinnamyl; (38) R = 4-chlorocinnamyl; (39) R = 4-bromocinnamyl; (40) R = 4-nitrocinnamyl; (41) R = 4-trifluoromethylcinnamyl; (42) R = 4-methylcinnamyl; (43) R = 4-methoxycinnamyl; (44) R = 3,4-(ethylenedioxy)cinnamyl; (45) R = 4-pyridyl; (46) R = 3-pyridyl; (47) R = 2-fluoro-3-pyridyl; (48) R = 2-chloro-3-pyridyl; (49) R = 2-bromo-3-pyridyl; (50) R = 2-methoxy-3-pyridyl; (51) R = 6-fluoro-3-pyridyl; (52) R = 6-chloro-3-pyridyl; (53) R = 6-bromo-3-pyridyl; or (54) R = 6-methoxy-3-pyridyl.

3. The method for preparing the andrographolide diester derivatives according to claim 1 or 2, characterized in that: The steps include: Step 1, reacting andrographolide of formula (a) with aluminum oxide to obtain an intermediate of formula (b); Step 2, reacting the intermediate represented by formula (b) with tert-butyldimethylsilyl chloride to prepare the intermediate represented by formula (c); Step 3, the intermediate represented by formula (c) is reduced with lithium aluminum tetrahydride to prepare the intermediate represented by formula (d); Step 4: The intermediate represented by formula (d) reacts with RCOOH to obtain andrographolide diester derivatives.

4. The method for preparing the andrographolide diester derivatives according to claim 3, characterized in that: The reaction in step 1 is carried out in the first organic solvent at a reaction temperature of 105-125°C.

5. The method for preparing the andrographolide diester derivatives according to claim 3, characterized in that: The reaction in step 2 is carried out in the second organic solvent, and the first organic base is added at the same time, and the reaction temperature is 55-65°C.

6. The method for preparing the andrographolide diester derivatives according to claim 3, characterized in that: The reaction in step three is carried out in a third organic solvent at a reaction temperature of -5 to 5°C.

7. The method for preparing the andrographolide diester derivatives according to claim 3, characterized in that: Step 4: The reaction is carried out in the fourth organic solvent, and a condensing agent and a second organic base are added simultaneously. The reaction temperature is 20-30°C.

8. The method for preparing the andrographolide diester derivatives according to claim 3, characterized in that: The RCOOH in the step 4 is selected from acetic acid, butyric acid, hexanoic acid, octanoic acid, nonanoic acid, decanoic acid, undecanoic acid, dodecanoic acid, benzoic acid, 2-fluorobenzoic acid, 3-fluorobenzoic acid, 4-fluorobenzoic acid, 2-chlorobenzoic acid, 3-chlorobenzoic acid, 4-chlorobenzoic acid, 2-bromobenzoic acid, 4-bromobenzoic acid, 3-cyanobenzoic acid, 4-cyanobenzoic acid, 2-nitrobenzoic acid, 3-nitrobenzoic acid, 4-nitrobenzoic acid, 2-trifluoromethylbenzoic acid, 3-trifluoromethylbenzoic acid, 4-trifluoromethylbenzoic acid, 2-methylbenzoic acid, 3-methylbenzoic acid, 4-methylbenzoic acid, 3-methoxybenzoic acid , 4-methoxybenzoic acid, 3,4-(methylenedioxy)benzoic acid, 3,4-(ethylenedioxy)benzoic acid, 2-methoxy-5-fluorobenzoic acid, 3,5-dimethylbenzoic acid, phenylacetic acid, cinnamic acid, 4-fluorocinnamic acid, 4-chlorocinnamic acid, 4-bromocinnamic acid, 4-nitrocinnamic acid, 4-trifluoromethylcinnamic acid, 4-methylcinnamic acid, 4-methoxycinnamic acid, 3,4-(ethylenedioxy)cinnamic acid, isonicotinic acid, nicotinic acid, 2-fluoronicotinic acid, 2-chloronicotinic acid, 2-bromonicotinic acid, 2-methoxynicotinic acid, 6-fluoronicotinic acid, 6-chloronicotinic acid, 6-bromonicotinic acid or 6-methoxynicotinic acid.

9. Use of the andrographolide diester derivatives according to claim 1 or 2 for preparing insecticides.

10. The use according to claim 9, characterized in that: The insecticide is oriental armyworm insecticide, apple yellow aphid insecticide and / or cinnabarinus spider mite insecticide.

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