Preparation method of a silicon-containing phenanthridine compound

Abstract

The present invention provides a method for preparing a silicon-containing phenanthridine compound. Using R-1,1'-biphenyl-2-isocyanide and R-silicon formic acid as starting materials, the reaction is carried out in the presence of a photocatalyst to obtain the silicon-containing phenanthridine compound. The reaction of the present invention does not require the participation of metals and does not require harsh reaction conditions such as adding bases. Only by using a photochemical method, the reaction can occur at room temperature, and it has the characteristics of simple reaction, low energy consumption, mild conditions and high efficiency.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of a silicon-containing phenanthridine compound. Background Art

[0002] The construction of complex organosilicon compounds by the formation of C–Si bonds through transition metal catalysis occupies a very important position in organic synthesis. The structural unit of silicon-based heteroaromatic hydrocarbons is commonly found in some bioactive organosilicon small molecule compounds, such as sila-haloperidol, sila-dimetracrine, etc.

[0003]

[0004] The efficient and selective synthesis method of phenanthridine compounds is of great significance in the fields of medicinal chemistry and materials science. Currently, various reported synthesis methods of phenanthridine compounds mainly include photochemical method, microwave promotion method and transition metal catalysis method. These methods usually require acid additives and are carried out under conditions of high temperature and multi-step tandem. There are very few reports on synthesis under mild conditions, so there are still certain limitations. Therefore, it is still very important to explore new methods for the efficient, simple and mild synthesis of phenanthridine and its derivatives. Summary of the Invention

[0005] Object of the Invention: Aiming at the above-mentioned prior art, a preparation method of a silicon-containing phenanthridine compound is provided, which does not require the use of expensive noble metal catalysts, has mild reaction conditions, good substrate universality and relatively high reaction yields.

[0006] Technical Solution: A preparation method of a silicon-containing phenanthridine compound, using R-1,1'-biphenyl-2-isocyanide and R-silanoic acid as starting materials, reacting under the condition of the presence of a photocatalyst to obtain the silicon-containing phenanthridine compound.

[0007] Preferably, the photocatalyst is 2,4,5,6-tetra(3,6-di-tert-butyl-9-carbazolyl)-1,3-benzenedicarbonitrile, and the reaction formula is:

[0008]

[0009] Preferably, the molar ratio of the feed of R-1,1'-biphenyl-2-isocyanide to R-silanoic acid is 1:1 - 2:1.

[0010] Preferably, the molar ratio of the feed of 2,4,5,6-tetra(3,6-di-tert-butyl-9-carbazolyl)-1,3-benzenedicarbonitrile is 1 - 5% of that of R-silanoic acid.

[0011] Preferably, the conditions of the reaction are as follows: the reaction solvent is tetrahydrofuran, the reaction light source is blue light, the reaction gas atmosphere is air, and the reaction time is 16 to 24 hours.

[0012] Beneficial effects: The preparation method of the silicon-containing phenanthridine compound of the present invention uses an isocyanide compound to react with a silicon radical to synthesize a silicon-containing phenanthridine compound, which is an important intermediate in drug synthesis. This reaction does not require the participation of metals and does not require harsh reaction conditions such as adding bases. It only needs to use a photochemical method and can participate in the reaction at room temperature. It has the characteristics of simple reaction, low energy consumption, mild conditions, and high efficiency, truly achieving "green chemistry". Description of the Drawings

[0013] Figure 1 1H NMR spectrum of compound 3 in Example 1; 1 1H NMR spectrum;

[0014] Figure 2 13C NMR spectrum of compound 3 in Example 1; 13 13C NMR spectrum;

[0015] Figure 3 1H NMR spectrum of compound 4 in Example 8; 1 1H NMR spectrum;

[0016] Figure 4 13C NMR spectrum of compound 4 in Example 8; 13 13C NMR spectrum;

[0017] Figure 5 HRMS spectrum of compound 4 in Example 8;

[0018] Figure 6 1H NMR spectrum of compound 5 in Example 9; 1 1H NMR spectrum;

[0019] Figure 7 13C NMR spectrum of compound 5 in Example 9; 13 13C NMR spectrum;

[0020] Figure 8 HRMS spectrum of compound 5 in Example 9;

[0021] Figure 9 1H NMR spectrum of compound 6 in Example 10; 1 1H NMR spectrum;

[0022] Figure 10 13C NMR spectrum of compound 6 in Example 10; 13 13C NMR spectrum;

[0023] Figure 11 HRMS spectrum of compound 6 in Example 10;

[0024] Figure 12 The HNMR spectrum of compound 7 in Example 11; 1

[0025] Figure 13 The C NMR spectrum of compound 7 in Example 11; 13

[0026] Figure 14 The HRMS spectrum of compound 7 in Example 11;

[0027] Figure 15 The HNMR spectrum of compound 8 in Example 12; 1

[0028] Figure 16 The C NMR spectrum of compound 8 in Example 12; 13

[0029] Figure 17 The HRMS spectrum of compound 8 in Example 12;

[0030] Figure 18 The HNMR spectrum of compound 9 in Example 13; 1

[0031] Figure 19 The C NMR spectrum of compound 9 in Example 13; 13

[0032] Figure 20 The HRMS spectrum of compound 9 in Example 13;

[0033] Figure 21 The HNMR spectrum of compound 10 in Example 14; 1

[0034] Figure 22 The C NMR spectrum of compound 10 in Example 14; 13

[0035] Figure 23 The HRMS spectrum of compound 10 in Example 14;

[0036] Figure 24 The HNMR spectrum of compound 11 in Example 15; 1

[0037] Figure 25 The C NMR spectrum of compound 11 in Example 15; 13

[0038] Figure 26 The HRMS spectrum of compound 11 in Example 15;​​​​​​​​​​

[0039] Figure 27 For the compound 12 in Example 16 1 HNMR spectrum;

[0040] Figure 28 For the compound 12 in Example 16 13 C NMR spectrum;

[0041] Figure 29 For the HRMS spectrum of the compound 12 in Example 16. Detailed implementation mode

[0042] The present invention will be further described below in conjunction with examples. The following examples are only used to more clearly illustrate the performance of the present invention and cannot be limited only to the following examples.

[0043] Example 1

[0044] Select two 10 mL Schlenk tubes with magnetic stirrers and branches, and add 26.8 mg of compound 1 (0.15 mmol), 28.4 mg of compound 2 (0.1 mmol), 1.3 mg of 2,4,5,6-tetra(3,6-di-tert-butyl-9-carbazolyl)-1,3-benzenedicarbonitrile (0.001 mmol, 1 mol%), and 2 mL of anhydrous tetrahydrofuran. React at room temperature for 16 hours under blue light irradiation. After the reaction is completed, the solvent is removed by rotary evaporation on a rotary evaporator, and compound 3 can be obtained by flash silica gel column chromatography (eluent petroleum ether:dichloromethane volume ratio = 15:1) with a yield of 74%. The reaction formula is as follows:

[0045]

[0046] The product structure characterization data are as follows:

[0047] 1 H NMR (400 MHz, CDCl3) δ 8.66 (d, J = 8.1 Hz, 2H), 8.48 (d, J = 8.1 Hz, 1H), 7.84 (d, J = 6.9 Hz, 6H), 7.78 (d, J = 8.1 Hz, 1H), 7.66 (t, J = 8.0 Hz, 1H), 7.42 (d, J = 24.2, 7.1 Hz, 6H), 7.26–7.20 (m, 1H), 1.45 (s, 9H) ppm, as Figure 1 shown.

[0048] 1313C NMR (101 MHz, CDCl3) δ 169.26, 144.12, 136.46, 134.99, 131.10, 130.63, 130.29, 129.72, 129.32, 128.39, 127.83, 127.58, 126.37, 123.61, 122.13, 122.06, 77.48, 76.84, 27.69, 20.04 ppm, as Figure 2 shown.

[0049] Example 2

[0050] According to the method of Example 1, except that 17.9 mg of Compound 1 (0.1 mmol) and 28.4 mg of Compound 2 (0.1 mmol) were added respectively. After silica gel column chromatography, the product was separated and the NMR spectrum was the same as that of Structure 3 in Example 1, with a yield of 50%.

[0051] Example 3

[0052] According to the method of Example 1, except that 35.8 mg of Compound 1 (0.2 mmol) and 28.4 mg of Compound 2 (0.1 mmol) were added respectively. After silica gel column chromatography, the product was separated and the NMR spectrum was the same as that of Structure 3 in Example 1, with a yield of 63%.

[0053] Example 4

[0054] According to the method of Example 1, except that 3.9 mg of 2,4,5,6 - tetra(3,6 - di - tert - butyl - 9 - carbazolyl) - 1,3 - benzonitrile (0.003 mmol, 3 mol%) was added. After silica gel column chromatography, the product was separated and the NMR spectrum was the same as that of Structure 3 in Example 1, with a yield of 55%.

[0055] Example 5

[0056] According to the method of Example 1, except that 6.5 mg of 2,4,5,6 - tetra(3,6 - di - tert - butyl - 9 - carbazolyl) - 1,3 - benzonitrile (0.005 mmol, 5 mol%) was added. After silica gel column chromatography, the product was separated and the NMR spectrum was the same as that of Structure 3 in Example 1, with a yield of 26%.

[0057] Example 6

[0058] According to the method of Example 1, except that the reaction was carried out at room temperature under blue - light irradiation for 20 hours. After silica gel column chromatography, the product was separated and the NMR spectrum was the same as that of Structure 3 in Example 1, with a yield of 74%.

[0059] Example 7

[0060] According to the method of Example 1, except that the reaction was carried out at room temperature for 24 hours under blue light irradiation, and after silica gel column chromatography, the product was separated, and the nuclear magnetic spectrum was the same as that of Structure 3 in Example 1, with a yield of 74%.

[0061] Example 8

[0062] According to the method of Example 1, except that the substrate used was 2-isocyano-4'-methyl-1,1'-biphenyl (29.0 mg, 0.15 mmol) and 28.4 mg of Compound 2 (0.1 mmol). After silica gel column chromatography, the desired 6-(tert-butyldiphenylsilyl)-8-methylpiperidine 4 was separated, with a yield of 53%. The structural formula of Compound 4 is as follows:

[0063]

[0064] The data for the structural characterization of the product are as follows:

[0065] 1 H NMR (400 MHz, CDCl3) δ (ppm) 8.59 (t, J = 7.2 Hz, 1H), 8.51 (t, J = 7.5 Hz, 1H), 8.36 (t, J = 7.3 Hz, 1H), 7.74 (d, J = 21.5 Hz, 6H), 7.48 (d, J = 6.3 Hz, 2H), 7.43–7.31 (m, 6H), 2.08 (s, 3H), 1.34 (s, 9H), as Figure 3 shown.

[0066] 13 C NMR (101 MHz, CDCl3) δ (ppm) 168.5, 143.4, 136.1, 134.9, 131.0, 130.6, 129.9, 128.8, 127.4, 123.3, 121.5, 76.4, 27.5, 21.1, 19.7, as Figure 4 shown.

[0067] HRMS (ESI): [M+H] + calcd for C 30 H 30 NSi + 432.2142, found: 432.2144, as Figure 5 shown.

[0068] Example 9

[0069] According to the method of Example 1, except that the substrate used was 2-isocyano-4'-methoxy-1,1'-biphenyl (31.4 mg, 0.15 mmol), 28.4 mg of Compound 2 (0.1 mmol), and after silica gel column chromatography, the desired 6-(tert-butyldiphenylsilyl)-8-methoxyphenanthrene 5 was obtained with a yield of 52%. The structural formula of Compound 5 is as follows:

[0070]

[0071] The structural characterization data of the product are as follows:

[0072] 1 H NMR (400 MHz, CDCl3) δ (ppm) 8.52 (t, J = 9.8 Hz, 2H), 8.36–8.32 (m, 1H), 7.78–7.65 (m, 7H), 7.39–7.29 (m, 6H), 7.10 (d, J = 2.6 Hz, 1H), 3.09 (s, 3H), 1.35 (s, 9H), as Figure 6 shown.

[0073] 13 C NMR (101 MHz, CDCl3) δ (ppm) 167.9, 157.3, 143.2, 136.2, 134.9, 131.5, 130.8, 129.0, 127.6, 125.1, 123.3, 121.3, 121.0, 76.5, 54.6, 27.56, 19.7, as Figure 7 shown.

[0074] HRMS (ESI): [M+H] + calcd for C 30 H 30 NOSi + 448.2091, found: 448.2088, as Figure 8 shown.

[0075] Example 10

[0076] According to the method of Example 1, except that the substrate used was 2-isocyano-1,1':4'-terphenyl (38.3 mg, 0.15 mmol), 28.4 mg of Compound 2 (0.1 mmol), and after silica gel column chromatography, the desired 6-(tert-butyldiphenylsilyl)-8-phenylphenanthrene 6 was obtained with a yield of 63%. The structural formula of Compound 6 is as follows:

[0077]

[0078] The structural characterization data of the product are as follows:

[0079] 1 1H NMR (400 MHz, CDCl3) δ (ppm) 8.58 (dd, J = 14.8, 8.3 Hz, 2H), 8.31 (d, J = 9.1 Hz, 1H), 7.96 (s, 1H), 7.85 (d, J = 8.6 Hz, 1H), 7.71 (d, J = 6.7 Hz, 6H), 7.35 (t, J = 7.3 Hz, 2H), 7.30–7.26 (m, 4H), 7.19–7.16 (m, 3H), 6.88–6.83 (m, 2H), 1.29 (s, 9H), as Figure 9 shown.

[0080] 13 13C NMR (101 MHz, CDCl3) δ (ppm) 169.3, 143.9, 139.7, 138.4, 136.2, 135.1, 130.8, 129.0, 128.4, 127.7, 127.7, 126.9, 123.1, 122.4, 121.8, 109.8, 109.8, 76.5, 27.7, 19.8, as Figure 10 shown.

[0081] HRMS (ESI): [M+H] + calcd for C 35 H 32 NSi + 494.2299, found: 494.2292, as Figure 11 shown.

[0082] Example 11

[0083] According to the method of Example 1, except that the substrate used was 4'-chloro-2-isocyano-1,1'-biphenyl (32.0 mg, 0.15 mmol), 28.4 mg of compound 2 (0.1 mmol), and after silica gel column chromatography, the desired 6-(tert-butyldiphenylsilyl)-8-chloroamidino 7 was obtained with a yield of 33%. The structural formula of compound 7 is as follows:

[0084]

[0085] The data for the structural characterization of the product are as follows:

[0086] 1 1H NMR (400 MHz, CDCl3) δ (ppm) 8.55 (t, J = 8.6 Hz, 2H), 8.37 (d, J = 7.9 Hz, 1H), 7.82–7.55 (m, 8H), 7.43–7.25 (m, 6H), 1.33 (s, 9H), asFigure 12 as shown

[0087] 13 C NMR(101MHz,CDCl3)δ(ppm)168.8,144.3,136.8,134.9,132.5,131.5,130.6,129.9,129.0,128.3,124.2,122.3,77.8,77.5,28.1,20.4, as Figure 13 shown

[0088] HRMS(ESI):[M+H] + calcd for C 29 H 27 ClNSi + 452.1596, found: 452.1570, as Figure 14 shown

[0089] Example 12

[0090] According to the method of Example 1, except that the substrate used was 4'-(tert-butyl)-2-isocyano-1,1'-biphenyl (35.3 mg, 0.15 mmol), 28.4 mg of Compound 2 (0.1 mmol), and after silica gel column chromatography, the desired 8-(tert-butyl)-6-(tert-butyldiphenylsilyl)phenanthrene 8 was obtained with a yield of 43%. The structural formula of Compound 8 is as follows:

[0091]

[0092] The structure characterization data of the product are as follows:

[0093] 1 H NMR(400MHz,CDCl3)δ(ppm)8.56(d,J = 19.2Hz,2H),8.35(s,1H),7.77(d,J = 7.1Hz,8H),7.33(d,J = 21.1Hz,6H),1.37(s,9H),0.90(s,9H), as Figure 15 shown

[0094] 13 C NMR(101MHz,CDCl3)δ(ppm)169.3,148.7,143.7,134.9,130.7,128.9,127.4,127.1,123.3,121.4,76.5,34.4,30.6,27.5,19.7, as Figure 16 shown

[0095] HRMS(ESI):[M+H] +Calculated for C 33 H 36 NSi + 474.2612, found: 474.2611, as Figure 17 shown.

[0096] Example 13

[0097] According to the method of Example 1, except that the substrate used was 2'-isocyano-[1,1'-biphenyl]-4-carbonitrile (30.6 mg, 0.15 mmol), 28.4 mg of Compound 2 (0.1 mmol). After silica gel column chromatography, the desired 6-(tert-butyldiphenylsilyl)phenanthridine-8-carbonitrile 9 was obtained with a yield of 43%. The structural formula of Compound 9 is as follows:

[0098]

[0099] The structure characterization data of the product are as follows:

[0100] 1 1H NMR (400 MHz, CDCl3) δ (ppm) 8.68 (d, J = 8.6 Hz, 1H), 8.60 (d, J = 8.2 Hz, 1H), 8.41 (d, J = 9.1 Hz, 1H), 8.02 (s, 1H), 7.90 (s, 1H), 7.83–7.75 (m, 2H), 7.74–7.65 (m, 4H), 7.47–7.25 (m, 6H), 1.33 (s, 9H), as Figure 18 shown

[0101] 13 13C NMR (101 MHz, CDCl3) δ (ppm) 168.9, 144.4, 136.0, 135.2, 133.7, 131.0, 129.5, 127.8, 123.1, 122.1, 118.1, 109.3, 31.7, 29.4, 22.4, 19.6, as Figure 19 shown

[0102] HRMS (ESI): [M + H] + Calculated for C 30 H 27 N2Si + 443.1938, found: 443.1937, as Figure 20 shown.

[0103] Example 14

[0104] According to the method of Example 1, except that the substrate used was 2-isocyano-5-methyl-1,1'-biphenyl (29.0 mg, 0.15 mmol), 28.4 mg of compound 2 (0.1 mmol), and after silica gel column chromatography, the desired 6-(tert-butyldiphenylsilyl)-2-methylpiperidine 10 was obtained with a yield of 61%. The structural formula of compound 10 is as follows:

[0105]

[0106] The structure characterization data of the product are as follows:

[0107] 1 H NMR (400 MHz, CDCl3) δ (ppm) 8.62 (d, J = 8.2 Hz, 1H), 8.42 (s, 1H), 8.28 (d, J = 8.3 Hz, 1H), 7.77–7.71 (m, 5H), 7.62 (t, J = 7.8 Hz, 2H), 7.36 (dd, J = 19.1, 7.4 Hz, 6H), 7.16 (t, J = 7.6 Hz, 1H), 2.69 (s, 3H), 1.35 (s, 9H), as Figure 21 shown.

[0108] 13 C NMR (101 MHz, CDCl3) δ (ppm) 167.5, 142.3, 137.2, 136.2, 134.8, 130.6, 130.5, 130.3, 130.1, 129.8, 129.2, 128.9, 127.5, 125.9, 123.1, 121.8, 121.3, 76.8, 76.5, 27.4, 22.0, 19.7, as Figure 22 shown.

[0109] HRMS (ESI): [M+H] + calcd for C 30 H 30 NSi + 432.2142, found: 432.2142, as Figure 23 shown.

[0110] Example 15

[0111] According to the method of Example 1, except that the substrate used was 5-chloro-2-isocyano-1,1'-biphenyl (32.0 mg, 0.15 mmol), 28.4 mg of compound 2 (0.1 mmol), and after silica gel column chromatography, the desired 6-(tert-butyldiphenylsilyl)-2-chlorophenanthrene 11 was obtained with a yield of 67%. The structural formula of compound 11 is as follows:

[0112]

[0113] The product structure characterization data are as follows:

[0114] 1 H NMR(400MHz,CDCl3)δ(ppm)8.56–8.44(m,2H),8.26(d,J = 8.7Hz,1H),7.68(d,J = 4.4Hz,7H),7.39–7.11(m,7H),1.28(s,9H), as Figure 24 shown.

[0115] 13 C NMR(101MHz,CDCl3)δ(ppm)169.4,142.1,136.1,134.4,132.2,129.1,127.6,126.7,121.9,121.4,76.5,27.3,19.7, as Figure 25 shown.

[0116] .HRMS(ESI):[M + H] + calcd for C 29 H 27 ClNSi + 452.1596,found:452.1594, as Figure 26 shown.

[0117] Example 16

[0118] According to the method of Example 1, except that the substrate used was 6 - isocyano - [1,1'-biphenyl] - 3 - carbonitrile (30.6 mg, 0.15 mmol), 28.4 mg of compound 2 (0.1 mmol), after silica gel column chromatography, the desired 6 - (tert - butyldiphenylsilyl) phenanthridine - 2 - carbonitrile 12 was separated with a yield of 27%. The structural formula of compound 12 is as follows:

[0119]

[0120] The product structure characterization data are as follows:

[0121] 1 H NMR(400MHz,CDCl3)δ(ppm)8.97(s,1H),8.57(d,J = 8.2Hz,1H),8.43(d,J = 8.4Hz,1H),7.97(d,J = 8.4Hz,1H),7.75(dd,J = 35.4,7.9Hz,6H),7.42–7.23(m,8H),1.31(s,9H), as Figure 27 shown.

[0122] 13 13C NMR (101 MHz, CDCl3) δ (ppm) 174.4, 145.3, 136.5, 134.5, 132.3, 131.2, 131.0, 130.7, 130.2, 130.1, 129.7, 128.3, 128.1, 127.9, 124.0, 122.2, 119.6, 110.9, 77.6, 30.0, 27.8, 20.2, as Figure 28 shown.

[0123] HRMS (ESI): [M+Na] + calcd for C 30 H 26 N2SiNa + 465.1757, found: 465.1764, as Figure 29 shown.

[0124] The above are only the preferred embodiments of the present invention. It should be pointed out that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and refinements can be made, and these improvements and refinements should also be regarded as the protection scope of the present invention.

Claims

1. A preparation method of a silicon-containing phenanthridine compound, characterized in that, It includes the following steps: Using compound 1 and compound 2 as starting materials, reacting in the presence of a photocatalyst to obtain compound 3. The reaction formula is as follows: ； Wherein, the photocatalyst is 2,4,5,6-tetra(3,6-di-tert-butyl-9-carbazolyl)-1,3-benzenedicarbonitrile, the reaction solvent is tetrahydrofuran, the reaction light source is blue light, the reaction gas atmosphere is air, and the reaction time is 16 - 24 hours; the molar ratio of the fed 2,4,5,6-tetra(3,6-di-tert-butyl-9-carbazolyl)-1,3-benzenedicarbonitrile is 1 - 3% of compound 2.

2. The preparation method of the silicon-containing phenanthridine compound according to claim 1, characterized in that: The molar ratio of the fed compound 1 and compound 2 is 1:1 - 2:1.

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