Preparation method of sulfonamide functionalized 4H-pyran compound

Abstract

The invention belongs to the technical field of organic synthesis, and provides a preparation method of a sulfamido-functionalized 4H-pyran compound, which comprises the following steps: in an organic solvent, under the catalysis of trifluoromethanesulfonic acid, carrying out cycloaddition reaction on 1, 3-diyne amide and 1, 3-diketone to prepare the 4H-pyran compound. The invention provides a route for preparing the 4H-pyran compound from 1, 3-diyne amide and 1, 3-diketone under the catalysis of Bronsted acid for the first time, and the route does not need a metal catalyst, is simple, practical and high in reaction efficiency, and is an organic synthesis reaction with a relatively large application prospect.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic synthesis, and relates to a preparation method of sulfonamide-functionalized 4H-pyran compounds, specifically to a reaction for preparing sulfonamide-functionalized 4H-pyran compounds from 1,3-diyne amides and 1,3-diketones catalyzed by Bronsted acid. Background Art

[0002] 4H-Pyran compounds are widely present in natural products and bioactive molecules (Bioorganic & Medicinal Chemistry, 2012, 20(23): 6831-9). Previously, the structures of 4H-pyran compounds were mostly constructed through the three-component reaction of aryl aldehydes, nitriles and carbonyl compounds (Journal of the Iranian Chemical Society, 2022, 19(9): 3721-68 and New Journal of Chemistry, 2015, 39(7): 5636-42). However, the 4H-pyran compounds synthesized by this method usually have an amino group attached to the 2-position of the 4H-pyran ring, and it is difficult to convert the amino group into a sulfonamide group through a two-step post-synthetic modification reaction. There are few reports on the reaction for directly synthesizing sulfonamide-functionalized 4H-pyran compounds in one step, and most of them use transition metals such as precious metals like gold and silver for catalysis, which have problems such as high price, harsh reaction conditions, and difficulty in large-scale production (Organic Letters, 2020, 22(11): 4478-82). Sulfonamide compounds can produce competitive antagonism with p-aminobenzoic acid necessary for bacterial growth, thus playing an antibacterial role. Introducing sulfonamide groups to improve the biological activity of compounds is an important means in organic chemistry and medicinal chemistry (Chinese Journal of Organic Chemistry, 2016, 36(3): 490-501). At present, directly synthesizing sulfonamide-functionalized 4H-pyran compounds by appropriate methods is still a challenge in organic synthetic chemistry, and the synthesis method of metal-free catalytic sulfonamide-functionalized 4H-pyran compounds has not been reported. Therefore, developing a new method that is simple, green, efficient, and low-cost to achieve the synthesis of amide-functionalized 4H-pyran compounds is challenging and meaningful.

[0003] To achieve the synthesis of the above-mentioned 4H-pyran compounds, the present invention provides a new method for the cycloaddition of 1,3-diyne amide compounds and 1,3-diketone compounds catalyzed by Brønsted acid to form sulfonamide-functionalized 4H-pyran compounds. This method can directly synthesize sulfonamide-functionalized 4H-pyran compounds in one step without post-modification, avoiding the use of metal catalysts, and has the advantages of mild reaction conditions and excellent yields. Summary of the Invention

[0004] The present invention provides a completely new reaction of 1,3-diyne amide compounds and 1,3-diketone compounds catalyzed by Brønsted acid for the synthesis of sulfonamide-functionalized 4H-pyran compounds.

[0005] The technical solution of the present invention:

[0006] A method for preparing 4H-pyran compounds, the steps are as follows:

[0007] Dissolve 1 molar equivalent of 1,3-diyne amide compound substrate A and 4 molar equivalents of 1,3-diketone compound substrate B in an organic solvent, and then add trifluoromethanesulfonic acid; stir the reaction mixture at room temperature for 6 hours; then, the product is separated and purified by silica gel column chromatography, using a petroleum ether:ethyl acetate system with a volume ratio of 2:1 as the eluent, and finally a yellow solid product of 4H-pyran compounds is obtained with a yield of 63 - 77%.

[0008] The preparation yield of 4H-pyran compounds is not less than 63%. The reaction formula is as follows:

[0009]

[0010] The reaction temperature is 25 °C and the reaction time is 6 h;

[0011] The structure of the 1,3-diyne amide compound A is as follows:

[0012]

[0013] The structure of the 1,3-diketone compound B is as follows:

[0014]

[0015] The reaction solvent is dichloromethane.

[0016] The dosage of the trifluoromethanesulfonic acid catalyst is 10 mol% of the dosage of 1,3-diyne amide.

[0017] The molar ratio of 1,3-diyne amide compound A to 1,3-diketone compound B is 1:4.

[0018] Advantages of the present invention:

[0019] (1) The present invention first realizes a reaction route for synthesizing 4H-pyran compounds based on the cycloaddition reaction of 1,3-diyne amides and 1,3-diketones. This synthesis method does not require post-modification and directly prepares sulfonamide-functionalized 4H-pyran compounds in a one-step process.

[0020] (2) The method proposed by the present invention avoids the use of metal catalysts, and the reaction conditions are mild, avoiding problems such as high price, harsh reaction conditions, and difficulty in large-scale production in the previous metal catalyst synthesis methods. It is an organic synthesis reaction with great application prospects. Description of the drawings

[0021] Figure 1 1H NMR nuclear magnetic spectrum of the sulfonamide-functionalized 4H-pyran compound prepared in Example 1 of the present invention 1 1H NMR nuclear magnetic spectrum.

[0022] Figure 2 13C NMR nuclear magnetic spectrum of the sulfonamide-functionalized 4H-pyran compound prepared in Example 1 of the present invention 13 13C NMR nuclear magnetic spectrum.

[0023] Figure 3 1H NMR nuclear magnetic spectrum of the sulfonamide-functionalized 4H-pyran compound prepared in Example 2 of the present invention 1 1H NMR nuclear magnetic spectrum.

[0024] Figure 4 13C NMR nuclear magnetic spectrum of the sulfonamide-functionalized 4H-pyran compound prepared in Example 2 of the present invention 13 13C NMR nuclear magnetic spectrum.

[0025] Figure 5 1H NMR nuclear magnetic spectrum of the sulfonamide-functionalized 4H-pyran compound prepared in Example 3 of the present invention 1 1H NMR nuclear magnetic spectrum.

[0026] Figure 6 13C NMR nuclear magnetic spectrum of the sulfonamide-functionalized 4H-pyran compound prepared in Example 3 of the present invention 13 13C NMR nuclear magnetic spectrum.

[0027] Figure 7 1H NMR nuclear magnetic spectrum of the sulfonamide-functionalized 4H-pyran compound prepared in Example 4 of the present invention 1 1H NMR nuclear magnetic spectrum.

[0028] Figure 8 13C NMR nuclear magnetic spectrum of the sulfonamide-functionalized 4H-pyran compound prepared in Example 4 of the present invention 13 13C NMR nuclear magnetic spectrum.

[0029] Figure 9 1H NMR spectrum of the sulfonamido-functionalized 4H-pyran compound prepared in Example 5 of the present invention 1 1H NMR spectrum

[0030] Figure 10 1H NMR spectrum of the sulfonamido-functionalized 4H-pyran compound prepared in Example 5 of the present invention 13 13C NMR spectrum

[0031] Figure 11 1H NMR spectrum of the sulfonamido-functionalized 4H-pyran compound prepared in Example 6 of the present invention 1 1H NMR spectrum

[0032] Figure 12 1H NMR spectrum of the sulfonamido-functionalized 4H-pyran compound prepared in Example 6 of the present invention 13 13C NMR spectrum

[0033] Figure 13 1H NMR spectrum of the sulfonamido-functionalized 4H-pyran compound prepared in Example 7 of the present invention 1 1H NMR spectrum

[0034] Figure 14 1H NMR spectrum of the sulfonamido-functionalized 4H-pyran compound prepared in Example 7 of the present invention 13 13C NMR spectrum

[0035] Figure 15 1H NMR spectrum of the sulfonamido-functionalized 4H-pyran compound prepared in Example 8 of the present invention 1 1H NMR spectrum

[0036] Figure 16 1H NMR spectrum of the sulfonamido-functionalized 4H-pyran compound prepared in Example 8 of the present invention 13 13C NMR spectrum

[0037] Figure 17 1H NMR spectrum of the sulfonamido-functionalized 4H-pyran compound prepared in Example 9 of the present invention 1 1H NMR spectrum

[0038] Figure 18 1H NMR spectrum of the sulfonamido-functionalized 4H-pyran compound prepared in Example 9 of the present invention 13 13C NMR spectrum

[0039] Figure 19 1H NMR spectrum of the sulfonamido-functionalized 4H-pyran compound prepared in Example 10 of the present invention 1 1H NMR spectrum

[0040] Figure 20 13C NMR spectrum of the sulfonamido-functionalized 4H-pyran compound prepared in Example 10 of the present invention 13 CNMR nuclear magnetic resonance spectrum Detailed implementation mode

[0041] The following further illustrates the specific implementation mode of the present invention in combination with technical solutions

[0042] Example 1: Reaction of N-benzyl-4-methyl-N-(phenyldibut-1,3-diyne-1-yl)benzenesulfonamide A1 with 1,3-cyclohexanedione B1 to prepare 4H-pyran compound N-benzyl-N-(4-benzylidene-5-oxo-5,6,7,8-tetrahydro-4H-chromen-2-yl)-4-methylbenzenesulfonamide

[0043] Substrate N-benzyl-4-methyl-N-(phenyldibut-1,3-diyne-1-yl)benzenesulfonamide A1 (38.5 mg, 0.1 mmol), 1,3-cyclohexanedione B1 (44.8 mg, 0.4 mmol) and dichloromethane (1.0 mL, 0.1 M) were successively added to a 5 mL reaction flask equipped with a polytetrafluoroethylene stir bar, and then trifluoromethanesulfonic acid (1.5 mg, 0.01 mmol) was added to the flask. The reaction mixture was stirred at room temperature (25 °C) for 6 hours. Subsequently, the product was separated and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 2:1) to obtain the yellow solid product N-benzyl-N-(4-benzylidene-5-oxo-5,6,7,8-tetrahydro-4H-chromen-2-yl)-4-methylbenzenesulfonamide (36.7 mg, yield 74%).

[0044]

[0045] 1 H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 8.0 Hz, 2H), 7.34 (d, J = 6.5 Hz, 3H), 7.29 (d, J = 8.0 Hz, 3H), 7.25 (s, 1H), 7.15 (d, J = 7.3 Hz, 1H), 7.09 (t, J = 7.4 Hz, 2H), 6.96 (d, J = 7.5 Hz, 2H), 5.95 (s, 1H), 5.69 (s, 1H), 4.37 (s, 2H), 2.45 (s, 3H), 2.35 (dt, J = 12.3, 6.4 Hz, 4H), 1.97 (p, J = 6.5 Hz, 2H); 1313C NMR (101 MHz, CDCl3) δ 199.45, 174.77, 144.23, 140.16, 136.42, 134.12, 131.69, 129.50, 129.07, 128.44, 128.20, 128.17, 118.22, 108.79, 52.49, 36.73, 27.55, 21.63, 21.22. HRMS (ESI-TOF) m / z calcd for C 30 H 27 NO4S (M - H) - 496.1583, found 496.1580.

[0046] Example 2: Reaction for preparing 4H-pyran compound N-benzyl-N-(4-benzylidene-5-oxo-4,5,6,7-tetrahydrocyclopenta[b]pyran-2-yl)-4-methylbenzenesulfonamide from N-benzyl-4-methyl-N-(phenyldibut-1,3-diyne-1-yl)benzenesulfonamide A1 and 1,3-cyclopentanedione B2.

[0047] Substrate N-benzyl-4-methyl-N-(phenyldibut-1,3-diyne-1-yl)benzenesulfonamide A1 (38.5 mg, 0.1 mmol), 1,3-cyclohexanedione B1 (39.2 mg, 0.4 mmol) and dichloromethane (1.0 mL, 0.1 M) were successively added into a 5 mL reaction flask equipped with a PTFE stir bar, and then trifluoromethanesulfonic acid (1.5 mg, 0.01 mmol) was added into the flask. The reaction mixture was stirred at room temperature (25 °C) for 6 hours. Then, the product was separated and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 2:1) to obtain the yellow solid product N-benzyl-N-(4-benzylidene-5-oxo-4,5,6,7-tetrahydrocyclopenta[b]pyran-2-yl)-4-methylbenzenesulfonamide (35.7 mg, yield 73%).

[0048]

[0049] 11H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 8.0 Hz, 2H), 7.34 (d, J = 6.5 Hz, 3H), 7.29 (d, J = 8.0 Hz, 3H), 7.25 (s, 1H), 7.15 (d, J = 7.3 Hz, 1H), 7.09 (t, J = 7.4 Hz, 2H), 6.96 (d, J = 7.5 Hz, 2H), 5.95 (s, 1H), 5.69 (s, 1H), 4.37 (s, 2H), 2.45 (s, 3H), 2.35 (dt, J = 12.3, 6.4 Hz, 4H), 1.97 (p, J = 6.5 Hz, 2H); 13 13C NMR (126 MHz, CDCl3) δ 205.43, 187.16, 144.46, 142.01, 136.16, 133.84, 131.23, 129.72, 129.59, 129.30, 129.11, 128.73, 128.59, 128.53, 128.48, 128.29, 128.26, 128.15, 128.00, 127.81, 127.75, 118.96, 109.26, 52.39, 34.19, 27.82, 21.67.

[0050] Example 3: Reaction of N-benzyl-4-methyl-N-(phenyldibut-1,3-dien-1-yl)benzenesulfonamide A1 with 5,5-dimethyl-1,3-cyclohexanedione B4 to prepare 4H-pyran compound N-benzyl-N-(4-benzylidene-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-chromen-2-yl)-4-methylbenzenesulfonamide.

[0051] Substrate N-benzyl-4-methyl-N-(phenyldibut-1,3-dien-1-yl)benzenesulfonamide A1 (38.5 mg, 0.1 mmol), 5,5-dimethyl-1,3-cyclohexanedione B4 (56.0 mg, 0.4 mmol) and dichloromethane (1.0 mL, 0.1 M) were successively added to a 5 mL reaction flask equipped with a PTFE stir bar, and then trifluoromethanesulfonic acid (1.5 mg, 0.01 mmol) was added to the flask. The reaction mixture was stirred at room temperature (25 °C) for 6 hours. Then, the product was separated and purified by silica gel column chromatography (petroleum ether:ethyl acetate = 2:1) to obtain the yellow solid product N-benzyl-N-(4-benzylidene-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-chromen-2-yl)-4-methylbenzenesulfonamide (35.1 mg, yield 67%).

[0052]

[0053] 11H NMR (500 MHz, CDCl3) δ 7.75 (d, J = 7.9 Hz, 2H), 7.37 (d, J = 7.7 Hz, 2H), 7.30 (t, J = 7.3 Hz, 5H), 7.18 (d, J = 7.6 Hz, 1H), 7.12 (t, J = 7.6 Hz, 2H), 6.96 (d, J = 7.4 Hz, 2H), 5.95 (s, 1H), 5.71 (s, 1H), 4.39 (s, 2H), 2.48 (s, 3H), 2.28 (s, 2H), 2.23 (s, 2H), 1.10 (s, 6H); 13 13C NMR (126 MHz, CDCl3) δ 199.37, 173.05, 144.21, 140.45, 136.44, 134.13, 131.74, 129.76, 129.55, 129.02, 128.84, 128.66, 128.53, 128.49, 128.42, 128.40, 128.21, 128.16, 128.14, 127.92, 117.62, 107.95, 52.45, 50.75, 41.23, 32.72, 29.73, 28.26, 21.64.

[0054] Example 4: Reaction of N-benzyl-N-[4-(4-methoxyphenyl)buta-1,3-diyne-1-yl]-4-methylbenzenesulfonamide A2 with 1,3-cyclohexanedione B1 to prepare 4H-pyran compound N-benzyl-N-(4-(4-methoxybenzylidene)-5-oxo-5,6,7,8-tetrahydro-4H-chromen-2-yl)-4-methylbenzenesulfonamide.

[0055] Substrate N-benzyl-N-[4-(4-methoxyphenyl)buta-1,3-diyne-1-yl]-4-methylbenzenesulfonamide A1 (41.5 mg, 0.1 mmol), 1,3-cyclohexanedione B1 (44.8 mg, 0.4 mmol) and dichloromethane (1.0 mL, 0.1 M) were successively added to a 5 mL reaction flask equipped with a PTFE stir bar, and then trifluoromethanesulfonic acid (1.5 mg, 0.01 mmol) was added to the flask. The reaction mixture was stirred at room temperature (25 °C) for 6 hours. Then, the product was separated and purified by silica gel column chromatography (petroleum ether:ethyl acetate = 2:1) to obtain the yellow solid product N-benzyl-N-(4-(4-methoxybenzylidene)-5-oxo-5,6,7,8-tetrahydro-4H-chromen-2-yl)-4-methylbenzenesulfonamide (40.0 mg, yield 76%).

[0056]

[0057] 11H NMR (400 MHz, CDCl3) δ 7.84 (d, J = 8.0 Hz, 2H), 7.39–7.30 (m, 2H), 7.24 (dd, J = 13.2, 5.7 Hz, 5H), 7.18 (d, J = 8.7 Hz, 2H), 6.84 (d, J = 8.8 Hz, 2H), 5.51 (s, 1H), 5.31 (s, 1H), 4.70 (s, 2H), 3.83 (s, 3H), 2.41 (t, J = 6.2 Hz, 2H), 2.30 (m, 5H), 1.95 (p, J = 6.3 Hz, 2H); 13 13C NMR (126 MHz, CDCl3) δ 199.36, 174.19, 159.94, 149.08, 144.37, 136.33, 134.77, 132.83, 129.75, 128.83, 128.44, 128.28, 128.02, 114.74, 113.95, 109.35, 98.42, 80.62, 55.40, 52.30, 36.65, 27.62, 21.54, 21.07.

[0058] Example 5: Reaction of N-benzyl-N-[4-(4-methoxyphenyl)buta-1,3-diyne-1-yl]-4-methylbenzenesulfonamide A2 with 1,3-cyclopentanedione B2 to prepare 4H-pyran compound N-benzyl-N-(4-(4-methoxybenzylidene)-5-oxo-4,5,6,7-tetrahydrocyclopenta[b]pyran-2-yl)-4-methylbenzenesulfonamide.

[0059] Substrate N-benzyl-N-[4-(4-methoxyphenyl)buta-1,3-diyne-1-yl]-4-methylbenzenesulfonamide A2 (41.5 mg, 0.1 mmol), 1,3-cyclopentanedione B2 (39.2 mg, 0.4 mmol) and dichloromethane (1.0 mL, 0.1 M) were successively added into a 5 mL reaction flask equipped with a PTFE stir bar, and then trifluoromethanesulfonic acid (1.5 mg, 0.01 mmol) was added to the flask. The reaction mixture was stirred at room temperature (25 °C) for 6 hours. Then, the product was separated and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 2:1) to obtain the yellow solid product N-benzyl-N-(4-(4-methoxybenzylidene)-5-oxo-4,5,6,7-tetrahydrocyclopenta[b]pyran-2-yl)-4-methylbenzenesulfonamide (35.3 mg, yield 69%).

[0060]

[0061] 11H NMR (400 MHz, CDCl3) δ 7.85 (d, J = 7.8 Hz, 2H), 7.37–7.25 (m, 7H), 7.25 (s, 2H), 7.16 (d, J = 8.7 Hz, 2H), 6.84 (d, J = 8.5 Hz, 2H), 5.48 (s, 1H), 5.34 (s, 1H), 4.79 (s, 2H), 3.88 (s, 3H), 2.63 (t, J = 5.1 Hz, 2H), 2.44 (d, J = 6.0 Hz, 2H), 2.30 (s, 3H); 13 13C NMR (101 MHz, CDCl3) δ 205.23, 186.45, 160.13, 144.51, 134.55, 132.87, 129.80, 128.91, 128.51, 128.40, 127.98, 114.50, 113.99, 109.38, 99.15, 55.39, 52.25, 34.27, 27.98, 21.51.

[0062] Example 6: Reaction of N-benzyl-N-[4-(4-methoxyphenyl)buta-1,3-diyn-1-yl]-4-methylbenzenesulfonamide A2 with 5-methyl-1,3-cyclohexanedione B3 to prepare 4H-pyran compound N-benzyl-N-(4-(4-methoxybenzylidene)-7-methyl-5-oxo-5,6,7,8-tetrahydro-4H-chromen-2-yl)-4-methylbenzenesulfonamide.

[0063] Substrate N-benzyl-N-[4-(4-methoxyphenyl)buta-1,3-diyn-1-yl]-4-methylbenzenesulfonamide A2 (41.5 mg, 0.1 mmol), 5-methyl-1,3-cyclohexanedione B3 (50.4 mg, 0.4 mmol) and dichloromethane (1.0 mL, 0.1 M) were successively added to a 5 mL reaction flask equipped with a PTFE stir bar, and then trifluoromethanesulfonic acid (1.5 mg, 0.01 mmol) was added to the flask. The reaction mixture was stirred at room temperature (25 °C) for 6 hours. Then, the product was separated and purified by silica gel column chromatography (petroleum ether:ethyl acetate = 2:1) to obtain the yellow solid product N-benzyl-N-(4-(4-methoxybenzylidene)-7-methyl-5-oxo-5,6,7,8-tetrahydro-4H-chromen-2-yl)-4-methylbenzenesulfonamide (34.1 mg, yield 63%).

[0064]

[0065] 11H NMR (400 MHz, CDCl3) δ 7.85 (d, J = 8.1 Hz, 2H), 7.31 (s, 3H), 7.26–7.15 (m, 6H), 6.84 (d, J = 8.7 Hz, 2H), 5.49 (s, 1H), 5.30 (s, 1H), 4.70 (s, 2H), 3.84 (s, 3H), 2.43–2.35 (m, 2H), 2.30 (s, 3H), 2.17 (s, 1H), 1.99 (dd, J = 16.2, 11.0 Hz, 2H), 1.06 (d, J = 5.8 Hz, 3H); 13 13C NMR (101 MHz, CDCl3) δ 199.30, 173.52, 159.95, 144.32, 132.82, 129.73, 128.84, 128.43, 128.27, 128.03, 114.79, 113.96, 109.08, 98.19, 80.66, 55.38, 52.29, 44.99, 35.63, 28.83, 21.51, 20.78.

[0066] Example 7: Reaction of N,4-dimethyl-N-(phenylbuta-1,3-diyn-1-yl)benzenesulfonamide A3 with 1,3-cyclohexanedione B1 to prepare 4H-pyran compound N-(4-benzylidene-5-oxo-5,6,7,8-tetrahydro-4H-chromen-2-yl)-N,4-dimethylbenzenesulfonamide.

[0067] Substrate N,4-dimethyl-N-(phenylbuta-1,3-diyn-1-yl)benzenesulfonamide A3 (30.9 mg, 0.1 mmol), 1,3-cyclohexanedione B1 (44.8 mg, 0.4 mmol) and dichloromethane (1.0 mL, 0.1 M) were successively added to a 5 mL reaction flask equipped with a PTFE stir bar, and then trifluoromethanesulfonic acid (1.5 mg, 0.01 mmol) was added to the flask. The reaction mixture was stirred at room temperature (25 °C) for 6 hours. Then, the product was separated and purified by silica gel column chromatography (petroleum ether:ethyl acetate = 2:1) to obtain the white solid product N-(4-benzylidene-5-oxo-5,6,7,8-tetrahydro-4H-chromen-2-yl)-N,4-dimethylbenzenesulfonamide (30.3 mg, yield 72%).

[0068]

[0069] 11H NMR (500 MHz, CDCl3) δ 7.67 (d, J = 8.1 Hz, 2H), 7.38 (d, J = 7.2 Hz, 2H), 7.27 (t, J = 7.4 Hz, 2H), 7.23 (d, J = 8.2 Hz, 3H), 5.98 (s, 1H), 5.59 (s, 1H), 2.91 (s, 3H), 2.37 (s, 3H), 2.29–2.22 (m, 4H), 1.87 (q, J = 6.5 Hz, 2H); 13 13C NMR (101 MHz, CDCl3) δ 199.44, 175.84, 144.20, 141.69, 135.91, 131.56, 129.54, 128.74, 128.62, 128.44, 128.42, 128.32, 127.92, 117.17, 107.21, 36.62, 36.54, 27.60, 21.59, 21.08.

[0070] Example 8: Reaction for preparing 4H-pyran compound N-(4-benzylidene-5-oxo-5,6,7,8-tetrahydro-4H-chromen-2-yl)-4-methyl-N-phenylbenzenesulfonamide from N,4-dimethyl-N-(phenylbuta-1,3-diyne-1-yl)benzenesulfonamide A4 and 1,3-cyclohexanedione B1.

[0071] Substrate N,4-dimethyl-N-(phenylbuta-1,3-diyne-1-yl)benzenesulfonamide A4 (37.1 mg, 0.1 mmol), 1,3-cyclohexanedione B1 (44.8 mg, 0.4 mmol) and dichloromethane (1.0 mL, 0.1 M) were successively added into a 5 mL reaction flask equipped with a PTFE stir bar, and then trifluoromethanesulfonic acid (1.5 mg, 0.01 mmol) was added into the flask. The reaction mixture was stirred at room temperature (25 °C) for 6 hours. Then, the product was separated and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 2:1) to obtain the white solid product N-(4-benzylidene-5-oxo-5,6,7,8-tetrahydro-4H-chromen-2-yl)-4-methyl-N-phenylbenzenesulfonamide (37.1 mg, yield 77%).

[0072]

[0073] 11H NMR (400 MHz, CDCl3) δ 7.58 (d, J = 7.6 Hz, 2H), 7.44 (d, J = 8.1 Hz, 2H), 7.34 (t, J = 7.5 Hz, 2H), 7.28 (d, J = 7.1 Hz, 1H), 7.23–7.14 (m, 7H), 6.05 (s, 1H), 5.91 (s, 1H), 2.55 (t, J = 6.1 Hz, 2H), 2.40 (s, 5H), 2.07 (q, J = 6.4 Hz, 2H). 13 13C NMR (101 MHz, CDCl3) δ 168.02, 163.25, 143.88, 137.73, 137.65, 134.63, 131.91, 130.81, 129.39, 128.53, 127.59, 127.38, 127.26, 121.31, 86.11, 48.99, 42.06, 21.61.

[0074] Example 9: Reaction for preparing 4H-pyran compound N-(4-benzylidene-5-oxo-5,6,7,8-tetrahydro-4H-chromen-2-yl)-4-methyl-N-phenylbenzenesulfonamide from N-phenyl-N-(phenybuta-1,3-diyn-1-yl)benzenesulfonamide A5 and 1,3-cyclopentanedione B2.

[0075] Substrate N-phenyl-N-(phenybuta-1,3-diyn-1-yl)benzenesulfonamide A5 (35.7 mg, 0.1 mmol), 1,3-cyclopentanedione B2 (39.2 mg, 0.4 mmol) and dichloromethane (1.0 mL, 0.1 M) were successively added into a 5 mL reaction flask equipped with a PTFE stir bar, and then trifluoromethanesulfonic acid (1.5 mg, 0.01 mmol) was added into the flask. The reaction mixture was stirred at room temperature (25 °C) for 6 hours. Then, the product was separated and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 2:1) to obtain white solid product N-(4-benzylidene-5-oxo-5,6,7,8-tetrahydro-4H-chromen-2-yl)-4-methyl-N-phenylbenzenesulfonamide (31.3 mg, yield 69%).

[0076]

[0077] 1 1H NMR (400 MHz, CDCl3) δ 7.71 (d, J = 7.7 Hz, 2H), 7.53 (t, J = 7.3 Hz, 1H), 7.39 (d, J = 7.7 Hz, 2H), 7.37–7.30 (m, 10H), 5.70 (s, 1H), 5.62 (s, 1H), 2.78–2.71 (m, 2H), 2.57–2.50 (m, 2H);13 13C NMR (101 MHz, CDCl3) δ 204.97, 186.51, 152.09, 139.16, 138.19, 133.37, 131.56, 129.34, 129.02, 128.92, 128.89, 128.76, 128.39, 128.10, 122.55, 110.40, 99.31, 81.75, 34.54, 27.71.

[0078] Example 10: Reaction for preparing 4H-pyran compound N-benzyl-N-(4-(2-hydroxyethylidene)-5-oxo-5,6,7,8-tetrahydro-4H-chromen-2-yl)-4-methylbenzenesulfonamide from N-benzyl-N-(5-hydroxypent-1,3-diyn-1-yl)-4-methylbenzenesulfonamide A6 and 1,3-cyclohexanedione B1.

[0079] Substrate N-benzyl-N-(5-hydroxypent-1,3-diyn-1-yl)-4-methylbenzenesulfonamide A6 (33.9 mg, 0.1 mmol), 1,3-cyclohexanedione B1 (44.8 mg, 0.4 mmol) and dichloromethane (1.0 mL, 0.1 M) were successively added into a 5 mL reaction flask equipped with a PTFE stir bar, and then trifluoromethanesulfonic acid (1.5 mg, 0.01 mmol) was added to the flask. The reaction mixture was stirred at room temperature (25 °C) for 6 hours. Subsequently, the product was separated and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 2:1) to obtain the yellow solid product N-benzyl-N-(4-(2-hydroxyethylidene)-5-oxo-5,6,7,8-tetrahydro-4H-chromen-2-yl)-4-methylbenzenesulfonamide (33.3 mg, yield 74%).

[0080]

[0081] 1 1H NMR (400 MHz, CDCl3) δ 7.53 (d, J = 8.4 Hz, 2H), 7.31–7.29 (m, 3H), 7.28 (d, J = 3.6 Hz, 1H), 7.26 (s, 2H), 7.24 (s, 1H), 6.47 (s, 1H), 6.18 (dd, J = 17.1, 10.7 Hz, 1H), 5.67–5.48 (m, 2H), 5.01 (s, 2H), 2.54 (t, J = 6.2 Hz, 2H), 2.43 (s, 3H), 2.30–2.23 (m, 2H), 1.95 (p, J = 6.4 Hz, 2H); 1313C NMR (101 MHz, CDCl3) δ 199.22, 176.54, 162.58, 157.73, 145.23, 136.40, 136.34, 130.50, 129.88, 129.78, 129.59, 128.74, 128.65, 128.60, 128.00, 127.90, 127.85, 127.78, 127.72, 127.55, 127.21, 123.10, 109.94, 77.24, 48.85, 36.48, 27.79, 21.66, 20.87.

Claims

1. A method for preparing a 4H-pyran compound, characterized in that, The steps are as follows: Dissolve 1 molar equivalent of 1,3 - diynamide compound substrate A and 4 molar equivalents of 1,3 - diketone compound substrate B in an organic solvent, and then add trifluoromethanesulfonic acid; stir the reaction mixture at room temperature for 6 hours; After that, the product is separated and purified by silica gel column chromatography, using a petroleum ether:ethyl acetate system with a volume ratio of 2:1 as the eluent to obtain a white or yellow solid product, a 4H - pyran compound; the reaction general formula is as follows:

2. The method for preparing a 4H - pyran compound according to claim 1, wherein, The structure of the 1,3 - diynamide compound A is as follows:

3. The method for preparing a 4H - pyran compound according to claim 1, wherein, The structure of the 1,3 - diketone compound B is as follows:

4. The method for preparing a 4H - pyran compound according to claim 1, wherein, The reaction solvent is dichloromethane.

5. The method for preparing a 4H - pyran compound according to claim 1, wherein, The dosage of the trifluoromethanesulfonic acid catalyst is 10 mol% of the dosage of 1,3 - diynamide.

6. The method for preparing a 4H - pyran compound according to claim 1, wherein, The molar ratio of the 1,3 - diynamide compound A to the 1,3 - diketone compound B is 1:4.

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