Method for preparing 9-(phenylsulfonyl)-xanthene derivatives by electrocatalysis

Abstract

The present invention belongs to the technical field of electrocatalytic preparation of xanthene derivatives. The present invention provides a method for electrocatalytically preparing 9-(phenylsulfonyl)-xanthene derivatives, including: adding aryl diazonium tetrafluoroborate derivatives, xanthene, DABSO, tetrabutylammonium hexafluorophosphate, acetonitrile and acetic acid in an electrolytic cell, passing a direct current, and reacting for 2 hours at a certain temperature and under nitrogen protection conditions. The present invention adopts electrocatalytic synthesis of 9-(phenylsulfonyl)-xanthene, which uses electric current as an oxidant, does not require an external oxidant and other metal catalysts, and also provides higher catalytic activity and lower reaction energy barrier for the reaction; and there is no need to pre-functionalize the substrate, with high atom economy and good functional group tolerance, so various substituted 9-(phenylsulfonyl)-xanthene can be obtained with good yield. In the reaction, low-toxicity and economical acetonitrile is used as a solvent, which avoids the use of highly toxic solvents and is green and environmentally friendly.

Description

Technical Field

[0001] The invention belongs to the technical field of electrocatalytic preparation of xanthene derivatives. Background Art

[0002] Benzenesulfonyl-xanthene is a class of derivatives containing an xanthene ring and a benzenesulfonyl group in its chemical structure, which has relatively unique biological activity and application potential. It mainly focuses on anti-tumor, anti-inflammatory, antibacterial and antiviral activities. Antibacterial activity: Some derivatives have significant inhibitory effects on Gram-positive and Gram-negative bacteria, and may achieve their antibacterial effects by destroying the cell membrane structure or interfering with cell wall synthesis. Anti-tumor activity: Some derivatives show inhibitory effects on a variety of cancer cells (such as breast cancer, lung cancer, etc.), and inhibit tumor growth by inducing cell apoptosis, inhibiting proliferation or blocking key signaling pathways. Anti-inflammatory activity: Benzenesulfonyl-substituted xanthene has the ability to inhibit cyclooxygenase (COX) and cytokine release, thereby reducing inflammatory responses. Antiviral activity: Some derivatives have inhibitory effects on a variety of viruses (such as influenza virus, hepatitis virus), and may achieve antiviral effects by inhibiting viral replication or interfering with the binding of viruses to host cells.

[0003] However, conventional methods for synthesizing these 9-(phenylsulfonyl)-xanthene derivatives require the use of highly toxic solvents, expensive metal catalysts, strong acids, strong bases, and strong oxidants, and the reaction times are long. Based on current research, we are committed to exploring new, efficient, simple, and environmentally friendly methods for synthesizing 9-substituted xanthene derivatives. Summary of the Invention

[0004] The present invention utilizes electrocatalytic synthesis of 9-(phenylsulfonyl)-xanthenes. This method uses electric current as the oxidant, eliminating the need for external oxidants or other metal catalysts. This method also provides higher catalytic activity and a lower reaction barrier. Furthermore, the method eliminates the need for substrate pre-functionalization, exhibits high atom economy and good functional group tolerance, and can produce various substituted 9-(phenylsulfonyl)-xanthenes in good yields. The reaction also utilizes low-toxic and economical acetonitrile as the solvent, avoiding the use of highly toxic solvents and achieving environmental friendliness.

[0005] Product solutions:

[0006]

[0007] R 1 is selected from hydrogen, methyl, methoxy, fluorine, chlorine, bromine, etc.; R 2 Selected from hydrogen, methyl, methoxy, fluorine, chlorine, bromine and the like.

[0008] This method uses electrocatalysis, using aryldiazonium tetrafluoroborate, xanthene, and DABSO as substrates, and acetonitrile and other inexpensive and less toxic reagents as solvents. The passage of an electric current replaces the oxidizing and reducing agents used in conventional reactions. This mild and green electrocatalytic synthesis method synthesizes 9-(phenylsulfonyl)-xanthene derivatives. BRIEF DESCRIPTION OF THE DRAWINGS

[0009] Figure 1 is the compound of Example 1 1 H NMR spectrum.

[0010] Figure 2 is the compound of Example 1 13 C NMR spectrum.

[0011] Figure 3 is the compound of Example 2 1 H NMR spectrum.

[0012] Figure 4 is the compound of Example 2 13 C NMR spectrum.

[0013] Figure 5 is the compound of Example 3 1 H NMR spectrum.

[0014] Figure 6 is the compound of Example 3 13 C NMR spectrum.

[0015] Figure 7 is the compound of Example 4 1 H NMR spectrum.

[0016] Figure 8 is the compound of Example 4 13 C NMR spectrum.

[0017] Figure 9 is the compound of Example 5 1 H NMR spectrum.

[0018] Figure 10 is the compound of Example 5 13 C NMR spectrum.

[0019] Figure 11 is the compound of Example 6 1 H NMR spectrum.

[0020] Figure 12 is the compound of Example 6 13 C NMR spectrum.

[0021] Figure 13 is the compound of Example 7 1 H NMR spectrum.

[0022] Figure 14 is the compound of Example 7 13 C NMR spectrum.

[0023] Figure 15 is the compound of Example 8 1 H NMR spectrum.

[0024] Figure 16 is the compound of Example 8 13 C NMR spectrum.

[0025] Figure 17 is the compound of Example 9 1 H NMR spectrum.

[0026] Figure 18 is the compound of Example 9 13 C NMR spectrum. DETAILED DESCRIPTION

[0027] Example

[0028] The present invention utilizes electrocatalytic synthesis of 9-(phenylsulfonyl)-xanthenes. This method uses electric current as the oxidant, eliminating the need for external oxidants or other metal catalysts. This method also provides higher catalytic activity and a lower reaction barrier. Furthermore, the method eliminates the need for substrate pre-functionalization, exhibits high atom economy and good functional group tolerance, and can produce various substituted 9-(phenylsulfonyl)-xanthenes in good yields. The reaction also utilizes low-toxic and economical acetonitrile as the solvent, avoiding the use of highly toxic solvents and achieving environmental friendliness.

[0029] The plan is as follows:

[0030]

[0031] Among them, R 1 is hydrogen, methyl, methoxy, fluorine, chlorine or bromine; R 2 is hydrogen, methyl, methoxy, fluorine, chlorine or bromine.

[0032] The raw materials include aryldiazonium tetrafluoroborate derivatives, xanthene, tetrabutylammonium hexafluorophosphate, 1,4-diazabicyclo[2.2.2]octane-1,4-diium-1,4-disulfinic acid (DABSO), acetonitrile and acetic acid.

[0033] The experimental equipment includes a carbon rod electrode (6 mm), a platinum sheet electrode (10*10*0.1 mm), a 25 ml electrolytic cell, a DC regulated power supply, and a magnet.

[0034] An aryldiazonium tetrafluoroborate derivative of Formula 1 (0.3-0.6 mmol), a xanthene of Formula 2 (0.2-0.4 mmol), 1,4-diazabicyclo[2.2.2]octane-1,4-diium-1,4-disulfinic acid (DABSO) (0.2-0.4 mmol), tetrabutylammonium hexafluorophosphate (0.2-0.4 mmol), acetonitrile (4-5 mL), acetic acid (0-1 mL), and a magnet were sequentially added to an electrolytic cell. A constant DC current was passed between the anode and cathode electrodes. The reaction was allowed to proceed at a constant temperature under nitrogen protection for 2 h. The reaction progress was monitored by thin-layer chromatography until the reaction was complete. Finally, the compound was separated and purified by silica gel column chromatography (petroleum ether:ethyl acetate) to obtain a compound of Formula 3. The reaction equation is as follows:

[0035]

[0036] In the equation: R 1 is hydrogen, methyl, methoxy, fluorine, chlorine or bromine; R 2 is hydrogen, methyl, methoxy, fluorine, chlorine or bromine.

[0037] Example 1:

[0038] The preparation method of this embodiment comprises the following steps:

[0039] 1a (0.3 mmol), 2a (0.2 mmol), DABSO (0.2 mmol), tetrabutylammonium hexafluorophosphate (0.2 mmol), acetonitrile (4 mL), acetic acid (1 mL), and a magnet were added to a reaction flask in sequence. A carbon rod was used as the anode and a platinum sheet was used as the cathode. A constant current of 10 mA was applied between the anode and cathode electrodes. The reaction was carried out at 40°C under a nitrogen atmosphere for 2 h. The reaction progress was monitored by thin-layer chromatography until completion. Finally, compound 3aa was isolated and purified by silica gel column chromatography to obtain compound 3aa in an 81% yield. The reaction equation is as follows:

[0040]

[0041] The compound spectrum data are as follows:

[0042] 1 H NMR (400MHz, CDCl3, ppm): δ7.58-7.55(m,2H),7.36-7.31(m,2H),7.18-7. 14(m,2H),6.90-6.86(m,4H),6.68-6.65(m,2H),5.39(s,1H),3.80(s,3H).

[0043] 13C NMR (100MHz, CDCl3, ppm): δ164.1,152.5,131.8,131.6,130.6,126.3,123.5,116.4,114.1,113.6,67.1,55.7.

[0044] Example 2:

[0045] The preparation method of this embodiment comprises the following steps:

[0046] 1b (0.3 mmol), 2a (0.2 mmol), DABSO (0.2 mmol), tetrabutylammonium hexafluorophosphate (0.2 mmol), acetonitrile (4 mL), acetic acid (1 mL), and a magnet were added to a reaction flask in sequence. A carbon rod was used as the anode and a platinum sheet was used as the cathode. A constant current of 10 mA was applied between the anode and cathode electrodes. The reaction was carried out at 40°C under a nitrogen atmosphere for 2 h. The reaction progress was monitored by thin-layer chromatography until completion. Finally, compound 3ba was isolated and purified by silica gel column chromatography in a 75% yield. The reaction equation is as follows:

[0047]

[0048] The compound spectrum data are as follows:

[0049] 1 H NMR (400MHz, CDCl3, ppm): δ7.56 (dd, J=7.6Hz, J=1.6Hz, 2H), 7.53-7.49 (m, 1H), 7.36-7.31 (m, 2H), 7.23-7.1 9(m,2H),7.18-7.14(m,2H),6.99(dd,J=8.4Hz,J=1.2Hz,2H),6.87(dd,J=8.4Hz,J=1.2Hz,2H),5.42(s,1H).

[0050] 13 C NMR (100MHz, CDCl3, ppm): δ152.5,134.8,134.0,131.5,130.7,129.7,128.3,123.5,116.4,113.8,67.3.

[0051] Example 3:

[0052] The preparation method of this embodiment comprises the following steps:

[0053] To a reaction flask, 1c (0.3 mmol), 2a (0.2 mmol), DABSO (0.2 mmol), tetrabutylammonium hexafluorophosphate (0.2 mmol), acetonitrile (4 mL), acetic acid (1 mL), and a magnet were added sequentially. A carbon rod was used as the anode and a platinum sheet was used as the cathode. A constant current of 10 mA was applied between the anode and cathode electrodes. The reaction was carried out at 40°C under a nitrogen atmosphere for 2 h. The reaction progress was monitored by thin-layer chromatography until completion. Finally, compound 3ca was isolated and purified by silica gel column chromatography to obtain compound 3ca in a 72% yield. The reaction equation is as follows:

[0054]

[0055] The compound spectrum data are as follows:

[0056] 1 H NMR (400MHz, CDCl3, ppm): δ7.56(d,J=7.6Hz,2H),7.34(t,J=7.8Hz,2H),7.16(t, J=7.4Hz,2H),7.01(d,J=7.6Hz,2H),6.90-6.85(q,4H),5.40(s,1H),2.36(s,3H).

[0057] 13 C NMR (100MHz, CDCl3, ppm): δ152.5, 145.0, 132.0, 131.5, 130.6, 129.7, 129.0, 123.5, 116.4, 114.0, 67.1, 21.8.

[0058] Example 4: The preparation method of this embodiment includes the following steps:

[0059] 1d (0.3 mmol), 2a (0.2 mmol), DABSO (0.2 mmol), tetrabutylammonium hexafluorophosphate (0.2 mmol), acetonitrile (4 mL), acetic acid (1 mL), and a magnet were added to a reaction flask in sequence. A carbon rod was used as the anode and a platinum sheet was used as the cathode. A constant current of 10 mA was applied between the anode and cathode electrodes. The reaction was carried out at 40°C under a nitrogen atmosphere for 2 h. The reaction progress was monitored by thin-layer chromatography until completion. Finally, compound 3da was isolated and purified by silica gel column chromatography to obtain compound 3da in a 73% yield. The reaction equation is as follows:

[0060]

[0061] The compound spectrum data are as follows:

[0062] 1H NMR (400MHz, CDCl3, ppm): δ7.60 (dd, J=8.0Hz, J=1.6Hz, 2H), 7.38-7.33 (m, 2H) ,7.18(t,J=7.6Hz,2H),6.96-6.93(m,2H),6.88(t,J=8.4Hz,4H),5.43(s,1H).

[0063] 13 C NMR (100MHz, CDCl3, ppm): δ166.3 (d, J=255.1Hz, 1C), 152.4, 132.5 (d, J=9.8Hz, 1C) ,131.6,130.7(d,J=3.1Hz,1C),123.7,116.5,115.7(d,J=22.4Hz,1C),113.8,67.3.

[0064] Example 5:

[0065] The preparation method of this embodiment comprises the following steps:

[0066] 1e (0.3 mmol), 2a (0.2 mmol), DABSO (0.2 mmol), tetrabutylammonium hexafluorophosphate (0.2 mmol), acetonitrile (4 mL), acetic acid (1 mL), and a magnet were added to a reaction flask. A carbon rod was used as the anode and a platinum sheet was used as the cathode. A constant current of 10 mA was applied between the anode and cathode electrodes. The reaction was carried out at 40°C under a nitrogen atmosphere for 2 h. The reaction progress was monitored by thin-layer chromatography until the reaction was complete. Finally, compound 3ea was isolated and purified by silica gel column chromatography to obtain compound 3ea in a 61% yield. The reaction equation is as follows:

[0067]

[0068] The compound spectrum data are as follows:

[0069] 1 H NMR (400MHz, CDCl3, ppm): δ7.58 (dd, J=7.6Hz, J=1.6Hz, 2H), 7.39-7.35 (m, 2H), 7.24-7.17 ( m, 4H), 6.91 (dd, J = 8.4Hz, J = 1.2Hz, 2H), 6.80-6.77 (m, 1H), 6.68-6.65 (m, 1H), 5.45 (s, 1H).

[0070] 13C NMR (100MHz, CDCl3, ppm): δ161.9 (d, J = 250.3Hz, 1C), 152.5, 136.8 (d, J = 26.4Hz, 1C), 131.5, 130.9, 130.0 (d, J = 2 9.6Hz, 1C), 125.6 (d, J = 3.4Hz, 1C), 123.7, 121.3 (d, J = 21.0Hz, 1C), 117.0 (d, J = 24.4Hz, 1C), 116.5, 113.5, 67.5.

[0071] Example 6:

[0072] The preparation method of this embodiment comprises the following steps:

[0073] To a reaction flask, 1f (0.3 mmol), 2a (0.2 mmol), DABSO (0.2 mmol), tetrabutylammonium hexafluorophosphate (0.2 mmol), acetonitrile (4 mL), acetic acid (1 mL), and a magnet were added sequentially. A carbon rod was used as the anode and a platinum sheet was used as the cathode. A constant current of 10 mA was applied between the anode and cathode electrodes. The reaction was carried out at 40°C under a nitrogen atmosphere for 2 h. The reaction progress was monitored by thin-layer chromatography until completion. Finally, compound 3fa was isolated and purified by silica gel column chromatography to obtain compound 3fa in a 71% yield. The reaction equation is as follows:

[0074]

[0075] The compound spectrum data are as follows:

[0076] 1 H NMR (400MHz, CDCl3, ppm): δ7.57 (dd, J=8.4Hz, J=1.6Hz, 4H), 7.38-7.34 (m, 2H), 7. 19-7.15(m,2H),6.92(dd,J=8.0Hz,J=1.6Hz,2H),6.66-6.63(m,2H),5.42(s,1H).

[0077] 13 C NMR (100MHz, CDCl3, ppm): δ152.5,137.6,134.7,131.5,130.9,130.9,123.7,116.6,113.6,102.4,67.3.

[0078] Example 7:

[0079] The preparation method of this embodiment comprises the following steps:

[0080] To a reaction flask, 1 g (0.3 mmol), 2a (0.2 mmol), DABSO (0.2 mmol), tetrabutylammonium hexafluorophosphate (0.2 mmol), acetonitrile (4 mL), acetic acid (1 mL), and a magnet were added sequentially. A carbon rod was used as the anode and a platinum sheet was used as the cathode. A constant current of 10 mA was applied between the anode and cathode electrodes. The reaction was carried out at 40°C under a nitrogen atmosphere for 2 h. The reaction progress was monitored by thin-layer chromatography until completion. Finally, compound 3ga was isolated and purified by silica gel column chromatography to obtain compound 3ga in a 65% yield. The reaction equation is as follows:

[0081]

[0082] The compound spectrum data are as follows:

[0083] 1 H NMR (400MHz, CDCl3, ppm): δ7.59 (dd, J=7.6Hz, J=1.6Hz, 2H), 7.57-7.54 (m, 2H), 7.49-7.41 (m, 5H), 7. 37-7.33(m,2H),7.20-7.16(m,2H),7.05-7.02(m,2H),6.89(dd,J=8.0Hz,J=1.2Hz,2H),5.46(s,1H).

[0084] 13 C NMR (100MHz, CDCl3, ppm): δ152.6,146.8,139.3,133.5,131.6,130.7,130.2,129.2,128.8,127.5,126.9,123.6,116.5,113.9,67.4.

[0085] Example 8:

[0086] The preparation method of this embodiment comprises the following steps:

[0087] 1a (0.3 mmol), 2b (0.2 mmol), DABSO (0.2 mmol), tetrabutylammonium hexafluorophosphate (0.2 mmol), acetonitrile (4 mL), acetic acid (1 mL), and a magnet were added to a reaction flask in sequence. A carbon rod was used as the anode and a platinum sheet was used as the cathode. A constant current of 10 mA was applied between the anode and cathode electrodes. The reaction was carried out at 40°C under a nitrogen atmosphere for 2 h. The reaction progress was monitored by thin-layer chromatography until the reaction was complete. Finally, compound 3ab was separated and purified by silica gel column chromatography to obtain compound 3ab in a 78% yield. The reaction equation is as follows:

[0088]

[0089] The compound spectrum data are as follows:

[0090] 1 H NMR (400MHz, CDCl3, ppm): δ7.52 (dd, J=7.6Hz, J=1.6Hz, 1H), 7.33-7.28 (m, 2H), 7.14-7.10 (m, 2H), 6.90-6.8 8(m,2H),6.87-6.85(m,1H),6.77(d,J=8.4Hz,1H),6.67-6.64(m,2H),5.31(s,1H),3.77(s,3H),2.35(s,3H).

[0091] 13 C NMR (100MHz, CDCl3, ppm): δ164.0,152.6,150.4,132.8,131.8,131.5,131.4,13 1.2,130.4,126.3,123.1,116.3,116.00,114.0,113.7,113.5,67.1,55.6,20.8.

[0092] Example 9:

[0093] The preparation method of this embodiment comprises the following steps:

[0094] 1a (0.3 mmol), 2c (0.2 mmol), DABSO (0.2 mmol), tetrabutylammonium hexafluorophosphate (0.2 mmol), acetonitrile (4 mL), acetic acid (1 mL), and a magnet were added to a reaction flask in sequence. A carbon rod was used as the anode and a platinum sheet was used as the cathode. A constant current of 10 mA was applied between the anode and cathode electrodes. The reaction was carried out at 40°C under a nitrogen atmosphere for 2 h. The reaction progress was monitored by thin-layer chromatography until completion. Finally, compound 3ac was isolated and purified by silica gel column chromatography to obtain compound 3ac in a 76% yield. The reaction equation is as follows:

[0095]

[0096] The compound spectrum data are as follows:

[0097] 1H NMR (400MHz, CDCl3, ppm): δ7.54 (dd, J=7.6Hz, J=1.6Hz, 1H), 7.50 (d, J=2.8Hz, 1H), 7.37-7.33 (m, 1H), 7.29 (dd, J=8.8Hz, J=2.8Hz, 1 H),7.19-7.15(m,1H),6.96-6.92(m,2H),6.90(d,J=2.8Hz,1H),6.85(d,J=8.8Hz,1H),6.72-6.68(m,2H),5.31(s,1H),3.82(s,3H);

[0098] 13 C NMR (100MHz, CDCl3, ppm): δ164.3,152.2,151.1,131.9,131.5,130.9,130.8 ,130.6,128.3,126.0,123.8,117.8,116.4,115.7,113.7,113.5,66.7,55.8.

[0099] The synthesis method of the present invention has the advantages of mild reaction conditions and low cost. In addition, the sulfonyl group in the reaction is derived from phenyl diazonium tetrafluoroborate and DABSO, which has high flexibility and can obtain a wider variety of target products.

Claims

1. A method for preparing 9-(phenylsulfonyl)-xanthene derivatives by electrocatalysis, characterized in that: include: Add aryldiazonium tetrafluoroborate derivatives, xanthene, DABSO, tetrabutylammonium hexafluorophosphate, acetonitrile and acetic acid into the electrolytic cell, pass a DC constant current, and react at a certain temperature under nitrogen protection for 2 hours; The equation for the reaction is: ; The R 1 is hydrogen, methyl, methoxy, phenyl, fluorine or iodine; The R 2 is hydrogen, methyl or chlorine; The DC constant current is 10 mA.

2. The method for electrocatalytically preparing 9-(phenylsulfonyl)-xanthene derivatives according to claim 1, characterized in that: The amount ratio of the aromatic diazonium tetrafluoroborate derivative, xanthene, DABSO and tetrabutylammonium hexafluorophosphate is 3:2:2:

2.

3. The method for electrocatalytically preparing 9-(phenylsulfonyl)-xanthene derivatives according to claim 1, characterized in that: The volume ratio of the acetonitrile to the acetic acid is 4:

1.

4. The method for electrocatalytically preparing 9-(phenylsulfonyl)-xanthene derivatives according to claim 1, characterized in that: The temperature was 40°C.

5. The method for electrocatalytically preparing 9-(phenylsulfonyl)-xanthene derivatives according to claim 1, characterized in that: The anode of the electrolytic cell is a carbon rod and the cathode is a platinum sheet.

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