Method for preparing 9-(benzenesulfonyl)-xanthene derivative through electro-catalysis

Abstract

The invention belongs to the technical field of preparation of xanthene derivatives through electro-catalysis. The invention provides a method for preparing a 9-(benzenesulfonyl)-xanthene derivative through electro-catalysis, which comprises the following steps: adding an aryl diazonium tetrafluoroborate derivative, xanthene, DABSO, tetrabutyl ammonium hexafluorophosphate, acetonitrile and acetic acid into an electrolytic tank, introducing direct-current constant current, and reacting for 2 hours at a certain temperature under the nitrogen protection condition. According to the method, the 9-(benzenesulfonyl)-xanthene is synthesized by adopting electro-catalysis, the method takes current as an oxidizing agent, an additional oxidizing agent and other metal catalysts are not needed, and meanwhile, higher catalytic activity and lower reaction energy barrier are provided for the reaction; the 9-(benzenesulfonyl)-xanthene compound has high atom economy and good functional group tolerance without pre-functionalization of a substrate, so that various substituted 9-(benzenesulfonyl)-xanthene can be obtained with good yield. In the reaction, low-toxicity and economical acetonitrile is used as a solvent, so that the use of a high-toxicity solvent is avoided, and the method is green and environment-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 xanthene rings and benzenesulfonyl groups in their chemical structures, which have relatively unique biological activities and application potentials. They are mainly concentrated in anti-tumor, anti-inflammatory, antibacterial and antiviral aspects. Antibacterial activity: Some derivatives have significant inhibitory effects on Gram-positive and Gram-negative bacteria, which may achieve their antibacterial effects by destroying the cell membrane structure or interfering with cell wall synthesis. Antitumor activity: Some derivatives show inhibitory effects on a variety of cancer cells (such as breast cancer, lung cancer, etc.), inhibiting 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), which may achieve antiviral effects by inhibiting viral replication or interfering with the binding of viruses to host cells.

[0003] However, in the process of synthesizing such 9-(phenylsulfonyl)-xanthene derivatives, conventional synthesis methods require the use of highly toxic solvents and expensive metal catalysts, strong acids, strong bases and strong oxidants, and the reaction time is long. Based on the current research situation, we have been committed to exploring new methods for synthesizing 9-substituted xanthene derivatives that are effective, simple and environmentally friendly. Summary of the invention

[0004] The present invention adopts electrocatalytic synthesis of 9-(phenylsulfonyl)-xanthene, which uses electric current as an oxidant, does not require the addition of an external oxidant and other metal catalysts, and also provides higher catalytic activity and lower reaction energy barriers for the reaction; and does not require pre-functionalization of the substrate, has high atom economy and good functional group tolerance, and thus can obtain various substituted 9-(phenylsulfonyl)-xanthene with good yields. In the reaction, low-toxic and economical acetonitrile is used as a solvent, avoiding the use of highly toxic solvents, and is green and environmentally friendly.

[0005] Product solution:

[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 to use aromatic diazonium tetrafluoroborate, xanthene, DABSO as reaction substrates, and acetonitrile and other cheap and less toxic reagents as solvents, and the current is passed to replace the oxidant and reductant in the conventional reaction. A mild and green electrocatalytic synthesis method is used to synthesize 9-(phenylsulfonyl)-xanthene derivatives. BRIEF DESCRIPTION OF THE DRAWINGS

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

[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 spectra.

[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 spectra.

[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 spectra.

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

[0017] Fig. 9 is the compound of Example 5 1 H NMR spectra.

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

[0019] Fig.11 is the compound of Example 6 1 H NMR spectra.

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

[0021] Fig.13 is the compound of Example 7 1 H NMR spectra.

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

[0023] Fig.15 is the compound of Example 8 1 H NMR spectra.

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

[0025] Fig.17 is the compound of Example 9 1 H NMR spectra.

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

[0027] Example

[0028] The present invention adopts electrocatalytic synthesis of 9-(phenylsulfonyl)-xanthene, which uses electric current as an oxidant, does not require the addition of an external oxidant and other metal catalysts, and also provides higher catalytic activity and lower reaction energy barriers for the reaction; and does not require pre-functionalization of the substrate, has high atom economy and good functional group tolerance, and thus can obtain various substituted 9-(phenylsulfonyl)-xanthene with good yields. In the reaction, low-toxic and economical acetonitrile is used as a solvent, avoiding the use of highly toxic solvents, and is green and environmentally friendly.

[0029] The solution 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] Add the aromatic diazo tetrafluoroborate derivative (0.3-0.6mmol) of the general formula 1, the xanthene (0.2-0.4mmol) of the general formula 2, 1,4-diazabicyclo[2.2.2]octane-1,4-diamine-1,4-disulfinic acid (DABSO) (0.2-0.4mmol), tetrabutylammonium hexafluorophosphate (0.2-0.4mmol), acetonitrile (4-5mL), acetic acid (0-1mL), and magnet in the electrolytic cell in sequence, pass a direct current between the electrode anode and the electrode cathode, react for 2h at a certain temperature and under nitrogen protection, and monitor the reaction progress by thin layer chromatography until the reaction is complete. Finally, separate and purify by silica gel column chromatography (petroleum ether: ethyl acetate) to obtain a compound with the general formula 3, and 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 magnet were added to the reaction bottle in sequence. A carbon rod was used as the anode and a platinum sheet was used as the cathode, respectively. A constant current of 10 mA was applied between the anode and cathode electrodes. The reaction was carried out in a nitrogen environment at 40°C for 2 h. The reaction progress was monitored by thin layer chromatography until the reaction was complete. Finally, compound 3aa was obtained by separation and purification by silica gel column chromatography with a yield of 81%. The reaction equation is as follows:

[0040]

[0041] The compound spectrum data are as follows:

[0042] 1 H NMR (400 MHz, CDCl 3 , 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] 13 C NMR (100 MHz, 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 (0.3mmol), 2a (0.2mmol), DABSO (0.2mmol), tetrabutylammonium hexafluorophosphate (0.2mmol), acetonitrile (4mL), acetic acid (1mL), and magnet were added to the reaction bottle in sequence. A carbon rod was used as the anode and a platinum sheet was used as the cathode, respectively. A constant current of 10mA was applied between the anode and cathode electrodes. The reaction was carried out in a nitrogen environment at 40°C for 2h. The reaction progress was monitored by thin layer chromatography until the reaction was complete. Finally, compound 3ba was obtained by separation and purification by silica gel column chromatography with a yield of 75%. The reaction equation is as follows:

[0047]

[0048] The compound spectrum data are as follows:

[0049] 1 H NMR (400 MHz, CDCl 3 ,ppm): δ7.56(dd,J=7.6Hz,J=1.6Hz,2H),7.53-7.49(m,1H),7.36-7.31(m,2H),7.23-7.19(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 (100 MHz, CDCl 3 , 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] 1c (0.3mmol), 2a (0.2mmol), DABSO (0.2mmol), tetrabutylammonium hexafluorophosphate (0.2mmol), acetonitrile (4mL), acetic acid (1mL), and magnet were added to the reaction bottle in sequence. A carbon rod was used as the anode and a platinum sheet was used as the cathode, respectively. A constant current of 10mA was applied between the anode and cathode electrodes. The reaction was carried out in a nitrogen environment at 40°C for 2h. The reaction progress was monitored by thin layer chromatography until the reaction was complete. Finally, compound 3ca was obtained by separation and purification by silica gel column chromatography with a yield of 72%. The reaction equation is as follows:

[0054]

[0055] The compound spectrum data are as follows:

[0056] 1 H NMR (400 MHz, CDCl 3 , 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 (100 MHz, CDCl 3 , 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 comprises the following steps:

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

[0060]

[0061] The compound spectrum data are as follows:

[0062] 1H NMR (400 MHz, CDCl 3 , 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 (100 MHz, CDCl 3 ,ppm): δ166.3(d,J=255.1Hz,1C),152.4,132.5(d,J=9.8Hz,1C),131.6,1 30.7(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 magnet were added to the reaction bottle in sequence. A carbon rod was used as the anode and a platinum sheet was used as the cathode, respectively. A constant current of 10 mA was applied between the anode and cathode electrodes. The reaction was carried out in a nitrogen environment at 40°C for 2 h. The reaction progress was monitored by thin layer chromatography until the reaction was complete. Finally, compound 3ea was obtained by separation and purification by silica gel column chromatography with a yield of 61%. The reaction equation is as follows:

[0067]

[0068] The compound spectrum data are as follows:

[0069] 1 H NMR (400 MHz, CDCl 3 ,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] 13 C NMR (100 MHz, CDCl 3,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=29.6Hz,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] 1f (0.3mmol), 2a (0.2mmol), DABSO (0.2mmol), tetrabutylammonium hexafluorophosphate (0.2mmol), acetonitrile (4mL), acetic acid (1mL), and magnet were added to the reaction bottle in sequence. A carbon rod was used as the anode and a platinum sheet was used as the cathode. A constant current of 10mA was applied between the anode and cathode electrodes. The reaction was carried out in a nitrogen environment at 40°C for 2h. The reaction progress was monitored by thin layer chromatography until the reaction was complete. Finally, the compound 3fa was separated and purified by silica gel column chromatography with a yield of 71%. The reaction equation is as follows:

[0074]

[0075] The compound spectrum data are as follows:

[0076] 1 H NMR (400 MHz, CDCl 3 , 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 (100 MHz, CDCl 3 , 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] 1g (0.3mmol), 2a (0.2mmol), DABSO (0.2mmol), tetrabutylammonium hexafluorophosphate (0.2mmol), acetonitrile (4mL), acetic acid (1mL), and magnet were added to the reaction bottle in sequence. A carbon rod was used as the anode and a platinum sheet was used as the cathode, respectively. A constant current of 10mA was applied between the anode and cathode electrodes. The reaction was carried out in a nitrogen environment at 40°C for 2h. The reaction progress was monitored by thin layer chromatography until the reaction was complete. Finally, compound 3ga was obtained by separation and purification by silica gel column chromatography with a yield of 65%. The reaction equation is as follows:

[0081]

[0082] The compound spectrum data are as follows:

[0083] 1 H NMR (400 MHz, CDCl 3 ,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 (100 MHz, CDCl 3 , 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 magnet were added to the reaction bottle 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 in a nitrogen environment at 40°C for 2 h. The reaction progress was monitored by thin layer chromatography until the reaction was complete. Finally, compound 3ab was obtained by separation and purification by silica gel column chromatography with a yield of 78%. The reaction equation is as follows:

[0088]

[0089] The compound spectrum data are as follows:

[0090] 1 H NMR (400 MHz, CDCl 3 ,ppm): δ7.52(dd,J=7.6Hz,J=1.6Hz,1H),7.33-7.28(m,2H),7.14-7.10(m,2H),6.90-6.88(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 (100 MHz, CDCl 3 ,ppm): δ164.0,152.6,150.4,132.8,131.8,131.5,131.4,131.2,130. 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 magnet were added to the reaction bottle in sequence. A carbon rod was used as the anode and a platinum sheet was used as the cathode, respectively. A constant current of 10 mA was applied between the anode and cathode electrodes. The reaction was carried out in a nitrogen environment at 40°C for 2 h. The reaction progress was monitored by thin layer chromatography until the reaction was complete. Finally, compound 3ac was obtained by separation and purification by silica gel column chromatography with a yield of 76%. The reaction equation is as follows:

[0095]

[0096] The compound spectrum data are as follows:

[0097] 1 H NMR (400 MHz, CDCl 3,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,1H),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 (100 MHz, CDCl 3 , 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 involved in 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 more types of target products.

Claims

1. A method for preparing 9-(phenylsulfonyl)-xanthene derivatives by electrocatalysis, characterized in that: include: Add aromatic diazonium tetrafluoroborate derivatives, xanthene, DABSO, tetrabutylammonium hexafluorophosphate, acetonitrile and acetic acid into the electrolytic cell, pass a DC constant current, and react for 2 hours at a certain temperature and under nitrogen protection.

2. The method for electrocatalytically preparing 9-(phenylsulfonyl)-xanthene derivatives according to claim 1, characterized in that: The aryldiazo tetrafluoroborate derivative has the following structural formula: Among them, R 1 is hydrogen, methyl, methoxy, phenyl, fluorine or iodine.

3. The method for electrocatalytically preparing 9-(phenylsulfonyl)-xanthene derivatives according to claim 1, characterized in that: The xanthene has the following structural formula: Among them, R 2 is hydrogen, methyl or chlorine.

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

2.

5. 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.

6. The method for electrocatalytically preparing 9-(phenylsulfonyl)-xanthene derivatives according to claim 1, characterized in that: The DC constant current is 10 mA.

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

8. 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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