Andrographolide diester derivative, preparation method and application

Abstract

The present invention discloses andrographolide diester derivatives, preparation methods, and applications. The general structural formula of this series of andrographolide diester derivatives is shown in Formula I. Studies have shown that some of the andrographolide diester derivatives disclosed herein have insecticidal activity against the oriental armyworm comparable to, or even higher than, the commercial botanical pesticide toosendanin. Some of the compounds also exhibit good contact activity against wingless adult apple aphids and adult female Tetranychus cinnabarinus mites, with significantly enhanced contact activity compared to the parent andrographolide. These compounds can be used to prepare highly effective, environmentally friendly, and low-toxic botanical pesticides.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and particularly 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 possess a variety of pharmaceutical and agricultural biological activities. In medicine, they exhibit anticancer [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] activities. Andrographolide and its derivatives also exhibit promising agricultural activities. 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 showed 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 through strategies such as epoxidation followed by 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 derivatives provided by the present invention is 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 the 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 the 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 solution 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] Alternatively, the reaction in step 2 is carried out in a second organic solvent while adding a first organic base at a reaction temperature of 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 can be tetrahydrofuran.

[0025] Alternatively, the reaction in step 4 is carried out in a fourth organic solvent, with the addition of a condensing agent and a second organic base, at a reaction temperature of 20-30°C. The fourth organic solvent may be dichloromethane. The condensing agent may be 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride. The second organic base may be 4-dimethylaminopyridine.

[0026] An optional solution 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 described herein can be used to prepare botanical pesticides. Some of these compounds exhibit significant biological activity against common agricultural pests such as the Oriental armyworm, the apple aphid, and the spider mite Tetranychus cinnabarinus, significantly enhancing their activity compared to the parent andrographolide. These compounds can be used to prepare highly effective, environmentally friendly, and low-toxic botanical pesticides. Furthermore, the preparation methods of the compounds described herein are simple, 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. All equivalent modifications made based on the technical solutions of this application fall within the scope of protection 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 shown as follows:

[0035]

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

[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) is reacted 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 a 115°C oil bath 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 mM DMF and stirred in a 60°C oil bath for 5 hours. After the reaction was complete, 10 mL of water was added and the mixture was extracted with dichloromethane (20 mL x 3). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, concentrated, and separated by column chromatography to obtain intermediate c in a 70% yield.

[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; lithium aluminum tetrahydride (1.0 mmol) was then added in batches and the reaction was continued with 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 in a yield of 45%.

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

[0045] 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-1,2-dimethyl-1 ... 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: early third-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); 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 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 placed on the bottom of a 9 cm diameter glass culture dish and water was added to keep it moist. Twelve early 3rd instar 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 leaf butterflies were immersed in the pre-prepared test solution and control solution for 3 seconds, and then naturally dried and fed to test insects; they were raised under the conditions of room temperature around 25℃, humidity 65%-80%, and light duration 12h / 12h; after the test insects finished eating the oat leaves, the leaf butterflies with the drug solution were added, and after raising for 48 hours, they were fed with fresh leaves without drug solution until they emerged; the food intake, number of survivors, and symptoms of the test insects were regularly recorded; 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 indicate that compound 22 exhibits potent stomach toxicity against Oriental armyworm larvae at a concentration of 1 mg / mL, with a final adjusted mortality rate of 59.5%, higher than the positive control, toosendanin (48.9%), and significantly higher activity than its parent, andrographolide (34.0%). It has the potential to be used in the preparation of 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-drip method:

[0275] The test compound was prepared in acetone at a concentration of 1 mg / mL (methomildazole at a concentration of 0.1 mg / mL). Acetone was used as a blank control. Selected aphids (uniformly sized, healthy, wingless adults) were dripped with 0.04 μL of the test solution onto their abdomens. The aphids were then transferred to 9 cm diameter Petri dishes lined with filter paper for moisture retention, with 30 aphids per dish. Each dish served as a replicate, and each treatment was repeated three times. The aphids were fed fresh leaves, with the petioles wrapped with wet absorbent cotton and then covered with gauze (or toilet paper). The aphids were housed under a photoperiod of 14h:10h L:D, a temperature of (25±1)°C, and a relative humidity of (50±7). The mortality of the aphids was observed and recorded after 24 and 48 hours. Aphid death was determined by complete immobility when a brush was applied to the legs and antennae. The 24- and 48-hour mortality (%) and adjusted mortality (%) of the aphids were calculated using the following formulas.

[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, and 46) was higher than 50%, which was significantly higher than that of the parent compound andrographolide. Therefore, they are expected to be used to prepare highly efficient, environmentally friendly, and low-toxic botanical aphidicide.

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

[0279] i. Test insects: adult female cinnabarinus spider mites (Tetranychus cinnabarinus Biosduval), a sensitive strain subcultured and reared 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 in an appropriate amount of acetone (2% of the target volume), and then adjust the concentration to 0.5 mg / mL using 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 lively female adult cinnabarinus mites of the same age, carefully and neatly stick their backs on the double-sided tape, stick about 35 mites on each slide, arrange them in 2 rows, put the slide with the test mites on an iron tray padded with a moist sponge, and place the iron tray 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 Soaking in medicine: Dip the end of the 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), and then put it back on the iron plate. Place it in a light incubator under the same breeding conditions. One slide is one treatment, and each treatment is repeated 3 times. 0.1‰ Tween 80 solution is used as the blank control.

[0286] ⑤ Results: 24 hours after treatment, slides were removed and examined under a stereomicroscope. Mites were gently touched with the tip of a brush. Mites whose chelicerae did not move were considered dead, and the number of dead individuals was recorded. Observation was continued for 72 hours. The mortality rate (%) and adjusted mortality rate (%) were calculated using the following formulas.

[0287]

[0288] Conclusion: The results shown in Table 3 indicate 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 compound andrographolide. Therefore, they are expected to be used to prepare highly efficient, environmentally friendly, and low-toxic botanical acaricides.

[0289] Obviously, the above embodiments of the present invention are merely examples for the purpose of clearly illustrating the present invention, and are not intended to limit the embodiments of the present invention. Those skilled in the art will appreciate that other variations or modifications can be made based on the above description. It is not necessary and impossible to enumerate all embodiments here. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention shall be included within the scope of protection 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 the following structures (1) to (15), (17) to (41), (43), (45) to (54): (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; (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; (43) R = 4-methoxycinnamyl; (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.

2. The method for preparing the andrographolide diester derivatives according to claim 1, characterized in that: The steps include: Step 1: reacting the andrographolide of formula (a) with aluminum oxide to prepare the intermediate of formula (b); ； ； Step 2: The intermediate represented by formula (b) reacts 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: reacting the intermediate represented by formula (d) with RCOOH to obtain andrographolide diester derivatives; 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, 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-methoxycinnamic 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.

3. The method for preparing the andrographolide diester derivatives according to claim 2, characterized in that: The reaction in step 1 is carried out in the first organic solvent at a reaction temperature of 105-125°C.

4. The method for preparing the andrographolide diester derivatives according to claim 2, wherein: 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.

5. The method for preparing the andrographolide diester derivatives according to claim 2, 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.

6. The method for preparing the andrographolide diester derivatives according to claim 2, characterized in that: Step 4: The reaction is carried out in the fourth organic solvent, while adding a condensing agent and a second organic base at a reaction temperature of 20-30°C.

7. The use of the andrographolide diester derivatives of claim 1 wherein R is represented by formula (6), (7), (9) to (15), (20) to (23), (25), (26), (28), (30), (32), (35), (37), (41), (45), (47) and (48) for the preparation of oriental armyworm insecticides.

8. The use of the andrographolide diester derivatives of claim 1 wherein R is represented by formula (9) to (11), (13), (15), (19), (20), (22), (31), (34), (38) to (40), (45), (46), (48), (49), (52) and (53) for the preparation of an insecticide for apple yellow aphids.

9. Use of the andrographolide diester derivatives of claim 1 wherein R is represented by formulas (1) to (15), (17) to (19), (21) to (36), (38) to (41), (43) and (45) to (54) for preparing insecticides against Tetranychus cinnabarinus.

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