Sulfonated pentamer derivatives and their preparation methods

Abstract

This invention discloses a sulfonated pentamer derivative and its preparation method. The structure of the sulfonated pentamer derivative is shown in formula (3), wherein R 1 For H or aryl, R 2 R is selected from one of aryl, haloaryl, or alkyl-substituted aryl groups. 3 The derivative is selected from aryl, haloaryl, alkoxy-substituted aryl, or alkyl-substituted aryl. This sulfonated pentamer derivative has a novel structure, and its preparation method is characterized by mild conditions and simple operation. The reaction is carried out at room temperature, requiring neither oxidizing nor reducing agents, nor the addition of metal catalysts. The synthetic steps are simple, with few side reactions and a high yield of the target product, making it highly valuable for widespread application.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and more specifically, to a sulfonated pentamer derivative and its preparation method. Background Technology

[0002] Lactams are among the most important five-membered nitrogen-containing skeletons and are widely found in a large number of products with biological and pharmaceutical activities. The main methods reported for synthesizing lactam compounds are as follows: (I) In 2021, Gu's group reported an experimental scheme for obtaining sulfonated succinimide containing separable E / Z configuration isomers through a silver-catalyzed radical reaction of aza-1,6-yne with sodium arylene sulfate (ArSO2Na). (II) Liu's group reported the preparation of lactams using a TBAI / TBHP aqueous phase catalytic oxidation system via a 5-exo / 6-endo tribicyclic reaction of 1,6-yne with sulfonyl hydrazine. (III) Yamaguchi's group reported a method for synthesizing δ-lactams through a cobalt- and photoredox dual-catalyzed olefin hydrogenation arylation reaction.

[0003] Currently, sulfur dioxide substitute DABCO(SO2)2 can also be used as a source of sulfur dioxide to synthesize sulfonyl compounds by fixing sulfur dioxide. This provides an efficient and direct route for generating sulfonyl compounds by inserting sulfur dioxide into small molecules.

[0004] While there are existing methods for synthesizing lactam derivatives, some of these methods require metal catalysis and the addition of specific ligands; some use stoichiometric amounts of oxidants or reductants as sacrificial reagents; and some use precious metals as catalysts, which are expensive and require high reaction temperatures, making them unsuitable for industrial production.

[0005] Therefore, it is necessary to provide a novel, green synthetic method for synthesizing sulfonated pentamer derivatives. Summary of the Invention

[0006] The purpose of this invention is to overcome the shortcomings of existing methods for synthesizing lactam derivatives, which require the use of metal catalysis and the addition of specific ligands, or the use of stoichiometric oxidants or reductants as sacrificial reagents. Some methods use precious metals as catalysts, which are expensive and have high reaction temperatures, making them unsuitable for industrial production. This invention provides a sulfonated penta-lactam derivative and its preparation method. The sulfonated penta-lactam derivative has a novel structure, and the preparation method has the advantages of mild conditions and simple operation. The reaction is carried out at room temperature, without the need for oxidants and reductants, or the addition of metal catalysts. The synthesis steps are simple, with few side reactions and high yield of the target product, making it highly valuable for promotion.

[0007] To achieve the above objectives, the present invention provides a sulfonated pentamer derivative, characterized in that the structure of the sulfonated pentamer derivative is as shown in formula (3). ; Among them, R 1 It is H or an aromatic group, R 2 R is selected from one of aryl, haloaryl, and alkyl-substituted aryl groups. 3 It is selected from one of aryl, haloaryl, alkoxy-substituted aryl, and alkyl-substituted aryl.

[0008] This invention also provides a method for preparing a sulfonated pentamic lactam derivative, the method comprising: mixing an N-(2-methylallyl)-N-phenylpropylamide derivative of formula (1), an aromatic diazonium tetrafluoroborate of formula (2), DABCO·(SO2)2, and a photocatalyst in the presence of a solvent and subjecting the mixture to a photocatalytic reaction. , ; Among them, R 1 For H or aryl, R 2 R is selected from one of aryl, haloaryl, or alkyl-substituted aryl groups. 3 It is selected from one of aryl, haloaryl, alkoxy-substituted aryl or alkyl-substituted aryl groups.

[0009] The present invention also provides a sulfonated pentamer derivative with the structure shown in formula (3) prepared by the preparation method described above. .

[0010] In the above technical solution, the preparation process of the sulfonated penta-lactam derivatives of the present invention is carried out at room temperature without heating, and does not require the use of oxidants or reducing agents or metal catalysts. The sulfonated penta-lactam derivatives can be obtained by mixing N-(2-methylallyl)-N-phenylpropylamide derivative, DABCO(SO2)2, photocatalyst and inexpensive aromatic diazonium tetrafluoroborate under light irradiation in the presence of a solvent. Compared with the prior art, the preparation method of the present invention has low cost, high synthesis efficiency, wide application range, is suitable for various substrate reactions, and has simple synthesis steps, few side reactions, high yield of target product, and high promotion value.

[0011] Other features and advantages of the present invention will be described in detail in the following detailed description section. Attached Figure Description

[0012] The accompanying drawings are provided to further illustrate the invention and form part of the specification. They are used together with the following detailed description to explain the invention, but do not constitute a limitation thereof. In the drawings: Figure 1 It is the product prepared in Example 1. 1 H NMR spectrum; Figure 2 It is the product prepared in Example 1. 13 C NMR spectrum; Figure 3 It is the product prepared in Example 2. 1 H NMR spectrum; Figure 4 It is the product prepared in Example 2. 13 C NMR spectrum; Figure 5 It is the product prepared in Example 3. 1 H NMR spectrum; Figure 6 It is the product prepared in Example 3. 13 C NMR spectrum; Figure 7 It is the product prepared in Example 4. 1 H NMR spectrum; Figure 8 It is the product prepared in Example 4. 13 C NMR spectrum; Figure 9 It is the product prepared in Example 5. 1 H NMR spectrum; Figure 10 It is the product prepared in Example 5. 13 C NMR spectrum; Figure 11 It is the product prepared in Example 6. 1 H NMR spectrum; Figure 12 It is the product prepared in Example 6. 13 C NMR spectrum; Figure 13 It is the product prepared in Example 7. 1 H NMR spectrum; Figure 14 It is the product prepared in Example 7. 13 C NMR spectrum.

[0013] Figure 15 It is the product prepared in Example 8. 1 H NMR spectrum; Figure 16 It is the product prepared in Example 8. 13 C NMR spectrum; Figure 17 It is the product prepared in Example 9. 1 H NMR spectrum; Figure 18 It is the product prepared in Example 9. 13 C NMR spectrum; Figure 19 It is the product prepared in Example 10. 1 H NMR spectrum; Figure 20 It is the product prepared in Example 10. 13 C NMR spectrum; Figure 21 This is the general reaction formula of the present invention. Detailed Implementation

[0014] The following provides a detailed description of specific embodiments of the present invention. It should be understood that the specific embodiments described herein are for illustrative and explanatory purposes only and are not intended to limit the scope of the invention.

[0015] The endpoints and any values ​​of the ranges disclosed herein are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of the various ranges, the endpoint values ​​of the various ranges and individual point values, and individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed herein.

[0016] The present invention provides a sulfonated pentamer derivative, characterized in that the structure of the sulfonated pentamer derivative is as shown in formula (3). ; Among them, R 1 For H or aryl, R 2 R is selected from one of aryl, haloaryl, and alkyl-substituted aryl groups. 3 It is selected from one of aryl, haloaryl, alkoxy-substituted aryl, and alkyl-substituted aryl.

[0017] The sulfonated pentamer derivative of the present invention has a novel structure, and the preparation method has the advantages of mild conditions and simple operation. The reaction is carried out at room temperature, without the need for oxidants and reducing agents, or the addition of metal catalysts. The synthesis steps are simple, with few side reactions and high yield of the target product, and it has high promotion value.

[0018] In a preferred embodiment of the present invention, the R 1 It is H or a monocyclic aryl group, preferably hydrogen or phenyl.

[0019] In a preferred embodiment of the present invention, R2 It is selected from one of monocyclic aryl, fluoroaryl, chloroaryl, bromoalkyl and methylaryl, preferably selected from one of phenyl, 4-fluorophenyl, 4-chlorophenyl, 3-chlorophenyl, 2-methylphenyl, 4-bromophenyl and 4-methylphenyl.

[0020] In a preferred embodiment of the present invention, R 3 It is selected from one of monocyclic aryl, fluoroaryl, chloroaryl, bromoaryl, C1-C4 alkoxy-substituted aryl and C1-C4 alkyl-substituted aryl, preferably selected from one of phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-methoxyphenyl, 2-methylphenyl, 3-methylphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-methylphenyl and 4-tert-butylphenyl.

[0021] In a preferred embodiment of the present invention, in order to achieve the above objective, the structure of the sulfonated pentamer derivative is shown in formula aj. .

[0022] This invention also provides a method for preparing a sulfonated pentamic lactam derivative, the method comprising: mixing an N-(2-methylallyl)-N-phenylpropylamide derivative of formula (1), an aromatic diazonium tetrafluoroborate of formula (2), DABCO·(SO2)2, a photocatalyst, and a solvent under an inert gas atmosphere and carrying out a photo-irradiation reaction. , ; Among them, R 1 For H or aryl, R 2 R is selected from one of aryl, haloaryl, or alkyl-substituted aryl groups. 3 It is selected from one of aryl, haloaryl, alkoxy-substituted aryl, or alkyl-substituted aryl.

[0023] This invention provides a simple preparation method for obtaining sulfonated pentamer derivatives. This method is low in cost, highly efficient, widely applicable, suitable for various substrate reactions, and features simple synthesis steps, few side reactions, high yield of the target product, and high promotional value.

[0024] In a preferred embodiment of the present invention, in order to improve the yield of the target product, the R... 1 It is H or a monocyclic aryl group, preferably hydrogen or phenyl.

[0025] In a preferred embodiment of the present invention, R 2It is selected from one of monocyclic aryl, fluoroaryl, chloroaryl, bromoalkyl and methylaryl, preferably from one of phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-methoxyphenyl, 2-methylphenyl, 3-methylphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-methylphenyl and 4-tert-butylphenyl.

[0026] In a preferred embodiment of the present invention, R 3 It is selected from one of monocyclic aryl, fluoroaryl, chloroaryl, bromoaryl, C1-C4 alkoxy-substituted aryl and C1-C4 alkyl-substituted aryl, preferably selected from one of phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-methoxyphenyl, 2-methylphenyl, 3-methylphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-methylphenyl and 4-tert-butylphenyl.

[0027] In a preferred embodiment of the present invention, in order to improve the yield of the target product, reduce side reactions, and facilitate the purification of subsequent products, the molar ratio of the N-(2-methylallyl)-N-phenylpropylamide derivative shown in formula (1), the aryl diazonium tetrafluoroborate shown in formula (2), and DABCO·(SO2)2 is 1:1.5-3:0.5-1.5. For example, specifically, it can be 1:1:0.5, 1:1:1, 1:1:1.5, 1:1:1, 1:2:1, 1:3:1, 1:1:0.5, 1:2:0.5, 1:3:0.5, 1:1:1.5, 1:2:1.5, or 1:3:1.5.

[0028] In a preferred embodiment of the present invention, in order to improve the yield of the target product, the photocatalyst is selected from one or more of N,N'-bis(2,6-diisopropylphenyl)-3,4,9,10-perylenetetracarboxydiimide, tris(2,2-bipyridine)chloride hexahydrate, and fac-Ir.

[0029] In a preferred embodiment of the present invention, in order to improve the yield of the target product, and since the photoreaction process requires the isolation of air, the photoreaction must at least meet the following conditions: the light source is selected from one or more of blue light, white light, and green light, preferably blue light; the time is 12-60h in an inert gas atmosphere, specifically 12h, 18h, 24h, 30h, 36h, 42h, 48h, 54h, or 60h; and the temperature is 15-30℃.

[0030] In a preferred embodiment of the present invention, the inert gas is argon and / or nitrogen.

[0031] In a preferred embodiment of the present invention, in order to improve reaction efficiency and the yield of the target product, the solvent is selected from one or more of 1,2-dimethoxyethane, acetonitrile, ethylene glycol dimethyl ether, tetrahydrofuran, 1,3-dioxopentane, and anhydrous ethanol.

[0032] In a preferred embodiment of the present invention, the preparation method further includes separation and purification, which includes: sequentially extracting, drying and concentrating the mixture obtained after the light irradiation reaction to obtain a crude product, and then purifying the crude product by column chromatography.

[0033] In a preferred embodiment of the present invention, the extractant used for extraction is ethyl acetate.

[0034] In a preferred embodiment of the present invention, the developing solvent used in the column chromatography is a conventional developing solvent formulation in the art, for example, it can be obtained by mixing petroleum ether and ethyl acetate in a volume ratio of 4:1.

[0035] In a preferred embodiment of the present invention, the drying can be a conventional drying method in the art, such as using anhydrous sodium sulfate as a desiccant.

[0036] The present invention also provides a sulfonated pentamer derivative with the structure shown in formula (3) prepared by the preparation method described above. .

[0037] The present invention will be described in detail below through examples, but the scope of protection of the present invention is not limited thereto. In the following examples, the drugs and pharmaceuticals are all conventional commercially available products.

[0038] Example 1 Synthetic method of 4-(((4-methoxyphenyl)sulfonyl)methyl)-4-methyl-3-methylene-1-phenylpyrrolidine-2-one: (1) Take 0.2 mmol of N-(2-methylallyl)-N-phenylpropionamide, 0.4 mmol of 4-methoxyphenyldiazotetrafluoroborate, 0.2 mmol of DABCO(SO2)2, and 2 mmol% of N,N'-bis(2,6-diisopropylphenyl)-3,4,9,10-perylenetetracarboxydiimide and place them in a 10 mL reaction tube. Add 4 mL of 1,2-dimethoxyethane under argon atmosphere and stir the mixture at 25 °C for 48 h under blue light irradiation. (2) The mixture obtained after the light reaction was extracted with ethyl acetate, dried with anhydrous sodium sulfate, concentrated under reduced pressure to obtain crude product, and purified by silica gel column chromatography (the developing solvent was obtained by mixing petroleum ether and ethyl acetate in a volume ratio of 4:1) to obtain an orange oily liquid. .

[0039] use 1 The prepared product was characterized by 1H NMR, and the results are as follows: Figure 1 As shown, the chemical shifts are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.84-7.81 (m, 2H), 7.74-7.72 (m, 2H), 7.42-7.38 (m, 2H), 7.21-7.17 (m, 1H), 7.02-7.00 (m, 2H), 6.13 (s, 1H), 5.32 (s,1H), 4.46 (d, J = 10.8 Hz, 1H), 3.87 (s, 3H), 3.78 (d, J = 10.8 Hz, 1H), 3.35 (d, J = 14.4 Hz, 1H), 3.30 (d, J = 14.4 Hz, 1H), 1.64 (s, 3H). use 13 The prepared product was characterized by C NMR, and the results are as follows: Figure 2 As shown, the chemical shifts are as follows: 13 C NMR (101 MHz, CDCl3) δ 165.1, 1641, 148.7, 139.1, 132.5, 130.0,129.1, 125.3, 120.0, 117.1, 114.8, 64.7, 56.7, 55.9, 38.4, 26.5. As can be seen from the above results, 4-(((4-methoxyphenyl)sulfonyl)methyl)-4-methyl-3-methylene-1-phenylpyrrolidone-2-one can be successfully prepared by the method of the present invention, and the calculated yield is 83%.

[0040] Example 2 Synthetic method of (E)-3-benzyl-4-(((4-methoxyphenyl)sulfonyl)methyl)-4-methyl-1-phenylpyrrolidine-2-one: (1) Take 0.2 mmol N-(2-methylallyl)-N,3-diphenylpropionamide, 0.4 mmol 4-methoxyphenyldiazotetrafluoroborate, 0.2 mmol DABCO(SO2)2, and 2 mmol% N,N'-bis(2,6-diisopropylphenyl)-3,4,9,10-perylenetetracarboxydiimide and place them in a 10 mL reaction tube. Add 4 mL of 1,2-dimethoxyethane under nitrogen purging and stir the reaction at 25 °C for 48 h under blue light irradiation. (2) The mixture obtained after the light reaction was extracted with ethyl acetate, dried with anhydrous sodium sulfate, concentrated under reduced pressure to obtain crude product, and purified by silica gel column chromatography (the developing solvent was obtained by mixing petroleum ether and ethyl acetate in a volume ratio of 4:1) to obtain an orange oily liquid. .

[0041] use 1 The prepared product was characterized by 1H NMR, and the results are as follows: Figure 3 As shown, the chemical shifts are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.76-7.74 (m, 2H), 7.68 – 7.64 (m, 3H), 7.44– 7.35 (m, 5H), 7.30 – 7.28 (m, 2H), 7.22-7.19 (m, 1H), 6.96 – 6.93 (m, 2H),4.39 (d, J = 10.4 Hz, 1H), 3.86 (s, 3H), 3.81 (d, J = 10.4 Hz, 1H), 3.55 (d, J =14.8 Hz, 1H), 3.20 (d, J = 14.4 Hz, 1H), 1.67 (s, 3H). use 13 The prepared product was characterized by C NMR, and the results are as follows: Figure 4 As shown, the chemical shifts are as follows: 13 C NMR (101 MHz, CDCl3) δ 166.2, 163.9, 139.4, 139.2, 134.8, 134.7,132.5, 129.8, 129.1, 129.1, 128.7, 125.2, 120.1, 114.6, 62.3, 58.2, 55.9,39.2, 26.2. As can be seen from the above results, the method described in this invention can successfully prepare (E)-3-benzylidene-4-(((4-methoxyphenyl)sulfonyl)methyl)-4-methyl-1-phenylpyrrolidine-2-one, and the calculated yield is 85%.

[0042] Example 3 Synthetic method of 1-(4-fluorophenyl)-4-(((4-methoxyphenyl)sulfonyl)methyl)-4-methyl-3-methylenepyrrolidine-2-one: (1) Take 0.2 mmol N-(4-fluorophenyl)-N-(2-methylallyl)propamide, 0.4 mmol 4-methoxyphenyldiazotetrafluoroborate, 0.2 mmol DABCO(SO2)2, and 2 mmol% N,N'-bis(2,6-diisopropylphenyl)-3,4,9,10-perylenetetracarboxydiimide and place them in a 10 mL reaction tube. Add 4 mL of tetrahydrofuran under argon gas and stir the reaction at 25 °C for 48 h under blue light irradiation. (2) The mixture obtained after the light reaction was extracted with ethyl acetate, dried with anhydrous sodium sulfate, concentrated under reduced pressure to obtain crude product, and purified by silica gel column chromatography (the developing solvent was obtained by mixing petroleum ether and ethyl acetate in a volume ratio of 4:1) to obtain an orange oily liquid. .

[0043] use 1 The prepared product was characterized by 1H NMR, and the results are as follows: Figure 5 As shown, the chemical shifts are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.83 – 7.81 (m, 2H), 7.72 – 7.69 (m, 2H), 7.11 – 7.07 (m, 2H), 7.02 – 7.00 (m, 2H), 6.13 (s, 1H), 5.33 (s, 1H), 4.46(d, J = 10.4 Hz, 1H), 3.88 (s, 3H), 3.76 (d, J = 10.4 Hz, 1H), 3.34 (d, J = 14.0Hz, 1H), 3.29 (d, J = 14.4 Hz, 1H), 1.64 (s, 3H). use 13 The prepared product was characterized by C NMR, and the results are as follows: Figure 6 As shown, the chemical shifts are as follows: 13 C NMR (101 MHz, CDCl3) δ 165.0, 164.1, 160.0(d, J = 243.9Hz), 148.5,135.2 (d, J CF = 2.8 Hz), 132.5, 130.0, 121.8 (d, J CF = 8.0 Hz), 117.2, 115.8(d, JC-F = 22.3Hz), 114.8, 64.7, 56.9, 55.9, 38.4, 26.5. As can be seen from the above results, 1-(4-fluorophenyl)-4-(((4-methoxyphenyl)sulfonyl)methyl)-4-methyl-3-methylenepyrrolidine-2-one can be successfully prepared by the method of the present invention, and the calculated yield is 78%.

[0044] Example 4 Synthetic method of 1-(4-chlorophenyl)-4-(((4-methoxyphenyl)sulfonyl)methyl)-4-methyl-3-methylenepyrrolidine-2-one: (1) Take 0.2 mmol of N-(4-chlorophenyl)-N-(2-methylallyl)propamide, 0.4 mmol of 4-methoxyphenyldiazotetrafluoroborate, 0.2 mmol of DABCO(SO2)2, and 2 mmol% N,N'-bis(2,6-diisopropylphenyl)-3,4,9,10-perylenetetracarboxydiimide and place them in a 10 mL reaction tube. Add 4 mL of 1,3-dioxolane under argon gas and stir the reaction at 25 °C for 48 h under blue light irradiation. (2) The mixture obtained after the light reaction was extracted with ethyl acetate, dried with anhydrous sodium sulfate, concentrated under reduced pressure to obtain crude product, and purified by silica gel column chromatography (the developing solvent was obtained by mixing petroleum ether and ethyl acetate in a volume ratio of 4:1) to obtain an orange oily liquid. .

[0045] use 1 The prepared product was characterized by 1H NMR, and the results are as follows: Figure 7 As shown. The chemical shifts are as follows: 1H NMR (400 MHz, CDCl3) δ 7.83-7.80 (m, 2H), 7.71 – 7.69 (m, 2H), 7.36– 7.34 (m, 2H), 7.02-7.00 (m, 2H), 6.13 (s, 1H), 5.34 (s, 1H), 4.44 (d, J =10.4 Hz, 1H), 3.87 (s, 3H), 3.75 (d, J = 10.8 Hz, 1H), 3.34 (d, J = 14.4 Hz, 1H), 3.28 (d, J = 14.4 Hz, 1H), 1.63 (s, 3H). use 13 The prepared product was characterized by C NMR, and the results are as follows: Figure 8 As shown. The chemical shifts are as follows: 13 C NMR (101 MHz, CDCl3) δ 165.1, 164.1, 148.3, 137.7, 132.4, 130.4,130.0, 129.1, 121.1, 117.5, 114.8, 64.6, 56.5, 55.9, 38.3, 26.6. As can be seen from the above results, 1-(4-chlorophenyl)-4-(((4-methoxyphenyl)sulfonyl)methyl)-4-methyl-3-methylenepyrrolidine-2-one can be successfully prepared by the method of the present invention, and the calculated yield is 77%.

[0046] Example 5 Synthetic method of 1-(4-bromophenyl)-4-(((4-methoxyphenyl)sulfonyl)methyl)-4-methyl-3-methylenepyrrolidine-2-one: (1) Take 0.2 mmol N-(4-bromophenyl)-N-(2-methylallyl)propamide, 0.4 mmol 4-methoxyphenyldiazotetrafluoroborate, 0.2 mmol DABCO(SO2)2, and 2 mmol% N,N'-bis(2,6-diisopropylphenyl)-3,4,9,10-perylenetetracarboxydiimide and place them in a 10 mL reaction tube. Add 4 mL of 1,2-dimethoxyethane under argon gas and stir the mixture at 30 °C for 48 h under blue light irradiation. (2) The mixture obtained after the light reaction was extracted with ethyl acetate, dried with anhydrous sodium sulfate, concentrated under reduced pressure to obtain crude product, and purified by silica gel column chromatography (the developing solvent was obtained by mixing petroleum ether and ethyl acetate in a volume ratio of 4:1) to obtain an orange oily liquid. .

[0047] use 1 The prepared product was characterized by 1H NMR, and the results are as follows: Figure 9 As shown, the chemical shifts are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.83 – 7.81 (m, 2H), 7.66 – 7.64 (m, 2H), 7.52 – 7.50 (m, 2H), 7.00 – 7.00 (m, 2H), 6.14 (s, 1H), 5.34 (s, 1H), 4.44(d, J = 10.8 Hz, 1H), 3.88 (s, 3H), 3.75 (d, J = 10.8 Hz, 1H), 3.34 (d, J = 14.0Hz, 1H), 3.28 (d, J = 14.4 Hz, 1H), 1.64 (s, 3H). use 13 The prepared product was characterized by C NMR, and the results are as follows: Figure 10 As shown, the chemical shifts are as follows: 13 C NMR (101 MHz, CDCl3) δ 165.1, 164.2, 148.4, 138.2, 132.4, 132.1,130.0, 121.4, 118.2, 117.6, 114.8, 64.6, 56.5, 55.9, 38.3, 26.6. As can be seen from the above results, 1-(4-bromophenyl)-4-(((4-methoxyphenyl)sulfonyl)methyl)-4-methyl-3-methylenepyrrolidine-2-one can be successfully prepared by the method of the present invention, and the calculated yield is 83%.

[0048] Example 6 Synthetic method of 4-(((4-methoxyphenyl)sulfonyl)methyl)-4-methyl-3-methylene-1-(p-tolyl)pyrrolidine-2-one: (1) Take 0.2 mmol N-(2-methylallyl)-N-(p-tolyl)propionamide, 0.4 mmol 4-methoxyphenyldiazotetrafluoroborate, 0.2 mmol DABCO(SO2)2, and 2 mmol% N,N'-bis(2,6-diisopropylphenyl)-3,4,9,10-perylenetetracarboxydiimide and place them in a 10 mL reaction tube. Add 4 mL of 1,2-dimethoxyethane under argon atmosphere and stir the reaction at 25 °C for 60 h under blue light irradiation. (2) The mixture obtained after the light reaction was extracted with ethyl acetate, dried with anhydrous sodium sulfate, concentrated under reduced pressure to obtain crude product, and purified by silica gel column chromatography (the developing solvent was obtained by mixing petroleum ether and ethyl acetate in a volume ratio of 4:1) to obtain an orange oily liquid. .

[0049] use 1 The prepared product was characterized by 1H NMR, and the results are as follows: Figure 11 As shown, the chemical shifts are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.83 – 7.81 (m, 2H), 7.62-7.59 (m, 2H), 7.21-7.19 (m, 2H), 7.01 – 7.00 (m, 2H), 6.10 (s, 1H), 5.30 (s, 1H), 4.43 (d, J = 10.4 Hz, 1H), 3.87 (s, 3H), 3.75 (d, J = 10.8 Hz, 1H), 3.34 (d, J = 14.0 Hz, 1H), 3.29 (d, J = 14.4 Hz, 1H), 2.34 (s, 3H), 1.63 (s, 3H). use 13 The prepared product was characterized by C NMR, and the results are as follows: Figure 12 As shown, the chemical shifts are as follows: 13 C NMR (101 MHz, CDCl3) δ 164.9, 164.1, 148.8, 136.6, 135.0, 132.5,130.0, 129.6, 120.0, 116.8, 114.8, 64.7, 56.8, 55.9, 38.4, 26.4, 21.0. As can be seen from the above results, 4-(((4-methoxyphenyl)sulfonyl)methyl)-4-methyl-3-methylene-1-(p-tolyl)pyrrolidine-2-one can be successfully prepared by the method of the present invention, and the calculated yield is 85%.

[0050] Example 7 Synthetic method of 4-methyl-3-methylene-1-phenyl-4-(phenylsulfonyl)methyl)pyrrolidine-2-one: (1) Take 0.2 mmol N-(2-methylallyl)-N-phenylpropionamide, 0.4 mmol diazonium tetrafluoroborate, 0.2 mmol DABCO(SO2)2, and 2 mmol%fac-Ir and place them in a 10 mL reaction tube. Add 4 mL of 1,2-dimethoxyethane under argon gas and stir the reaction at 25 °C for 48 h under blue light irradiation. (2) The mixture obtained after the light reaction was extracted with ethyl acetate, dried with anhydrous sodium sulfate, concentrated under reduced pressure to obtain crude product, and purified by silica gel column chromatography (the developing solvent was obtained by mixing petroleum ether and ethyl acetate in a volume ratio of 4:1) to obtain an orange oily liquid. .

[0051] use 1 The prepared product was characterized by 1H NMR, and the results are as follows: Figure 13 As shown, the chemical shifts are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.93-7.91 (m, 2H), 7.75-7.73 (m, 2H), 7.69-7.66 (m, 1H), 7.60-7.56 (3, 2H), 7.43-7.39 (m, 2H), 7.22-7.19 (m, 1H), 6.14(s, 1H), 5.34 (s, 1H), 4.48 (d, J = 10.8 Hz, 1H), 3.82 (d, J = 10.8 Hz, 1H), 3.38(d, J = 14.4 Hz, 1H), 3.32 (d, J = 14.4 Hz, 1H), 1.67 (s, 3H). use 13 The prepared product was characterized by C NMR, and the results are as follows: Figure 14 As shown, the chemical shifts are as follows: 13C NMR (101 MHz, CDCl3) δ 165.0, 148.6, 140.9, 139.1, 134.2, 129.7,129.1, 127.8, 125.3, 120.0, 117.2, 64.4, 56.7, 38.4, 26.5. As can be seen from the above results, the method described in this invention can successfully prepare 4-methyl-3-methylene-1-phenyl-4-(phenylsulfonyl)methyl)pyrrolidine-2-one, and the calculated yield is 72%.

[0052] Example 8 Synthetic method of 4-(((4-fluorophenyl)sulfonyl)methyl)-4-methyl-3-methylene-1-phenylpyrrolidone-2-one: (1) Take 0.2 mmol N-(2-methylallyl)-N-phenylpropionamide, 0.4 mmol 4-fluoroborate diazonium tetrafluoroborate, 0.2 mmol DABCO(SO2)2, and 2 mmol% N,N'-bis(2,6-diisopropylphenyl)-3,4,9,10-perylenetetracarboxydiimide and place them in a 10 mL reaction tube. Add 4 mL of anhydrous ethanol under argon gas and stir the reaction at 25 °C for 48 h under blue light irradiation. (2) The mixture obtained after the light reaction was extracted with ethyl acetate, dried with anhydrous sodium sulfate, concentrated under reduced pressure to obtain crude product, and purified by silica gel column chromatography (the developing solvent was obtained by mixing petroleum ether and ethyl acetate in a volume ratio of 4:1) to obtain an orange oily liquid. .

[0053] use 1 The prepared product was characterized by 1H NMR, and the results are as follows: Figure 15 As shown, the chemical shifts are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.95-7.92 (m, 2H), 7.75-7.73 (m, 2H), 7.43-7.39 (m, 2H), 7.27-7.19 (m 3H), 6.15 (s, 1H), 5.34 (s, 1H), 4.48 (d, J = 10.8Hz, 1H), 3.82 (d, J = 10.8 Hz, 1H), 3.36 (d, J = 14.0 Hz, 1H), 3.31 (d, J= 14.0Hz, 1H), 1.67 (s, 3H). use 13 The prepared product was characterized by C NMR, and the results are as follows: Figure 16 As shown, the chemical shifts are as follows: 13 C NMR (101 MHz, CDCl3) δ 166.1 (d, J C-F = 256 Hz), 165.0, 148.5,139.0, 137.0 (d, J C-F = 3.0 Hz), 130.8 (d, J C-F =10.0 Hz), 129.2, 125.4, 120.0,117.3, 117.0(d, J C-F = 22.0 Hz), , 64.6, 56.7, 38.4, 26.4 As can be seen from the above results, 4-(((4-fluorophenyl)sulfonyl)methyl)-4-methyl-3-methylene-1-phenylpyrrolidone-2-one can be successfully prepared by the method of the present invention, and the calculated yield is 70%.

[0054] Example 9 Synthetic method of 4-(((4-(tert-butyl)phenyl)sulfonyl)methyl)-4-methyl-3-methylene-1-phenylpyrrolidone-2-one: (1) Take 0.2 mmol N-(2-methylallyl)-N-phenylpropionamide, 0.4 mmol 4-tert-butylboronic acid diazonium fluoroborate, 0.2 mmol DABCO(SO2)2, and 4 mmol% N,N'-bis(2,6-diisopropylphenyl)-3,4,9,10-perylenetetracarboxydiimide and place them in a 10 mL reaction tube. Add 4 mL of 1,2-dimethoxyethane under argon gas and stir the mixture at 25 °C for 48 h under blue light irradiation. (2) The mixture obtained after the light reaction was extracted with ethyl acetate, dried with anhydrous sodium sulfate, concentrated under reduced pressure to obtain crude product, and purified by silica gel column chromatography (the developing solvent was obtained by mixing petroleum ether and ethyl acetate in a volume ratio of 4:1) to obtain an orange oily liquid. .

[0055] use 1 The prepared product was characterized by 1H NMR, and the results are as follows: Figure 17 As shown, the chemical shifts are as follows: 1H NMR (400 MHz, CDCl3) δ 7.84-7.82 (m, 2H), 7.73-7.71 (m, 2H), 7.58-7.56 (m, 2H), 7.42-7.38 (m, 2H), 7.21-7.17 (m, 1H), 6.13 (s, 1H), 5.34 (s,1H), 4.42 (d, J = 10.8 Hz, 1H), 3.78 (d, J = 10.4 Hz, 1H), 3.37 (d, J = 14.4 Hz, 1H), 3.31 (d, J = 14.0 Hz, 1H), 1.67 (s, 3H), 1.34 (s, 9H). use 13 The prepared product was characterized by C NMR, and the results are as follows: Figure 18 As shown, the chemical shifts are as follows: 13 C NMR (101 MHz, CDCl3) δ 165.0, 158.3, 148.8, 139.1, 137.9, 129.1,127.7, 126.7, 125.3, 120.0, 117.1, 64.4, 56.7, 38.7, 35.4, 31.2, 26.4. As can be seen from the above results, 4-(((4-(tert-butyl)phenyl)sulfonyl)methyl)-4-methyl-3-methylene-1-phenylpyrrolidone-2-one can be successfully prepared by the method of the present invention, and the calculated yield is 89%.

[0056] Example 10 Synthetic method of 4-methyl-3-methylene-1-phenyl-4-(toluenesulfonylmethyl)pyrrolidine-2-one: (1) Take 0.2 mmol N-(2-methylallyl)-N-phenylpropionamide, 0.4 mmol 4-methylboronic acid diazonium fluoroborate, 0.2 mmol DABCO(SO2)2, and 2 mmol% tris(2,2-bipyridine)chloride hexahydrate and place them in a 10 mL reaction tube. Add 4 mL of 1,2-dimethoxyethane under argon gas and stir the reaction at 25 °C for 48 h under blue light irradiation. (2) The mixture obtained after the light reaction was extracted with ethyl acetate, dried with anhydrous sodium sulfate, concentrated under reduced pressure to obtain crude product, and purified by silica gel column chromatography (the developing solvent was obtained by mixing petroleum ether and ethyl acetate in a volume ratio of 4:1) to obtain an orange oily liquid. .

[0057] use 1 The prepared product was characterized by 1H NMR, and the results are as follows: Figure 19 As shown, the chemical shifts are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.80-7.78 (m, 2H), 7.75 – 7.73 (m, 2H), 7.43– 7.35 (m, 4H), 7.22-7.18 (m, 1H), 6.14 (s, 1H), 5.33 (s, 1H), 4.46 (d, J =10.4 Hz, 1H), 3.80 (d, J = 10.4 Hz, 1H), 3.36 (d, J = 14.4 Hz, 1H), 3.30 (d, J =14.4 Hz, 1H), 2.45 (s, 3H), 1.66 (s, 3H). use 13 The prepared product was characterized by C NMR, and the results are as follows: Figure 20 As shown, the chemical shifts are as follows: 13 C NMR (101 MHz, CDCl3) δ 165.1, 148.8, 145.3, 139.1, 138.1, 130.3,129.1, 127.8, 125.3, 120.0, 117.1, 64.5, 56.7, 38.4, 26.4, 21.8. As can be seen from the above results, 4-methyl-3-methylene-1-phenyl-4-(toluenesulfonylmethyl)pyrrolidone-2-one can be successfully prepared by the method of the present invention, and the calculated yield is 83%.

[0058] The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the scope of the technical concept of the present invention, various simple modifications can be made to the technical solution of the present invention, and these simple modifications all fall within the protection scope of the present invention.

[0059] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any suitable manner without contradiction. In order to avoid unnecessary repetition, the present invention will not describe the various possible combinations separately.

[0060] Furthermore, various different embodiments of the present invention can be combined in any way, as long as they do not violate the spirit of the present invention, they should also be regarded as the content disclosed by the present invention.

Claims

1. A method for preparing a sulfonated pentamyl lactam derivative, characterized in that, The preparation method includes: mixing N-(2-methylallyl)-N-phenylpropylamide derivative, aromatic diazonium tetrafluoroborate, DABCO·(SO2)2, photocatalyst, and solvent under inert gas protection and carrying out a photo-irradiation reaction. The N-(2-methylallyl)-N-phenylpropylamide derivative is , , , , or The aromatic diazonium tetrafluoroborate is , , , or ; The photocatalyst is selected from one or more of N,N'-bis(2,6-diisopropylphenyl)-3,4,9,10-perylenetetracarboxydiimide, tris(2,2-bipyridine)chloride hexahydrate, or fac-Ir; the solvent is selected from one or more of 1,2-dimethoxyethane, acetonitrile, ethylene glycol dimethyl ether, tetrahydrofuran, 1,3-dioxopentane, and anhydrous ethanol; the photoreaction must meet at least the following conditions: the light source is blue light; the atmosphere is inert gas; the time is 12-60 h; and the temperature is 15-30 °C. The structure of the sulfonated pentamer derivative is shown in formula aj. 。 2. The preparation method according to claim 1, characterized in that, The molar ratio of the N-(2-methylallyl)-N-phenylpropylamide derivative, the aromatic diazonium tetrafluoroborate, and the DABCO·(SO2)2 is 1:1-3:0.5-1.

5.

3. The preparation method according to claim 1, characterized in that, The inert gas is argon and / or nitrogen.

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