Preparation method of alkyl thioether phenanthridine

Abstract

The invention discloses a preparation method of alkyl thioether phenanthridine, and belongs to the field of organic synthesis. The invention solves the problems of limited types of alkyl sulfur reagents, high toxicity and instability of precursor reagents, complex synthesis of thioether-containing skeleton molecules, severe and severe reaction conditions and difficulty in removal of metal catalysts in the prior art. The method comprises the following steps: 1, mixing triphenylphosphine sulfur and a trifluoromethanesulfonic acid alkyl reagent, and reacting at room temperature to obtain alkyl sulfur triphenylphosphonium trifluoromethanesulfonate; and 2, mixing the 2-isocyanide-1, 1 '-biphenyl derivative and alkyl sulfur triphenyl phosphonium trifluoromethanesulfonate, and carrying out blue light irradiation reaction to obtain the alkyl sulfide phenanthridine. The preparation method disclosed by the invention is used for preparing the alkyl sulfide phenanthridine.

Description

Technical Field

[0001] The invention belongs to the field of organic synthesis. Background Art

[0002] Sulfide compounds have diverse chemical properties and important biological activities, and have shown great application value in the fields of medicine and chemical biology. For example, thioridazine, a drug used to treat schizophrenia and other diseases, pergolide, a drug used to treat Parkinson's disease and other diseases, and methionine, which is essential for the human body, all contain important alkyl sulfide groups.

[0003] Alkylthio radicals are generally obtained from two common sulfur reagents, methylthiophenol and dimethyl sulfide. Alkylthiols and alkyl disulfide compounds have the disadvantages of being highly toxic and smelly, volatile and unstable, and requiring more safety measures when handling. In addition, thiophenol compounds need to generate sulfur radicals under the conditions of an initiator. Commonly used free radical initiators generally include peroxides, azobisisobutyronitrile or organic boron, etc. The use of these free radical initiators often requires higher temperatures or excessive additives, and has a greater impact on the compatibility of the functional groups of the reaction.

[0004] Most natural products and drug molecule derivatives contain chiral structures. During the methylthio modification process using traditional chemical methods, the harsh and intensive reaction conditions may affect the stereoconfiguration of drugs and natural products, and the involvement of transition metal catalysts may bring about metal residue problems. Summary of the invention

[0005] The present invention aims to solve the problems that the existing alkyl sulfide reagents are limited in types, the precursor reagents are highly toxic and unstable, the synthesis of sulfide-containing skeleton molecules is complicated, the reaction conditions are harsh and severe, and the metal catalyst is difficult to remove, and provides a method for preparing alkyl sulfide phenanthridine.

[0006] A method for preparing an alkyl sulfide phenanthridine is carried out according to the following steps:

[0007] 1. mixing triphenylphosphine sulfide and trifluoromethanesulfonic acid alkyl reagent, and then adding an organic solvent to obtain a mixed solution I, reacting the mixed solution I at room temperature, and then removing the solvent and washing the solid to obtain alkylthiotriphenylphosphonium trifluoromethanesulfonate;

[0008] The molar ratio of triphenylphosphine sulfide to trifluoromethanesulfonic acid alkyl reagent is 1:(1-1.5);

[0009] The general structural formula of the alkylthiotriphenylphosphonium trifluoromethanesulfonate is Wherein R1 is methyl, ethyl, propyl or butyl;

[0010] 2. Under a nitrogen atmosphere, a 2-isocyanate-1,1'-biphenyl derivative and an alkylthiotriphenylphosphonium trifluoromethanesulfonate are mixed, and then an organic solvent is added to obtain a mixed solution II. Under a nitrogen atmosphere, the mixed solution II is irradiated with blue light for reaction, and then the solvent is removed and purified by chromatography to obtain an alkylthioether phenanthridine;

[0011] The molar ratio of the 2-isocyanate-1,1'-biphenyl derivative to the alkylthiotriphenylphosphonium trifluoromethanesulfonate is 1:(1.5-2);

[0012] The general structural formula of the 2-isocyanate-1,1'-biphenyl derivative is wherein Ar1 is phenyl, phenyl substituted with methyl at the 4th position or phenyl substituted with halogen at the 4th position, and Ar2 is phenyl, phenyl substituted with alkyl at the 4th position, phenyl substituted with alkoxy at the 4th position, phenyl substituted with halogen at the 4th position, phenyl substituted with phenyl at the 4th position or phenyl substituted with ester at the 4th position;

[0013] The structural formula of the alkyl sulfide phenanthridine is Wherein R1 is methyl, ethyl, propyl or butyl, Ar1 is phenyl, phenyl substituted with methyl at the 4th position or phenyl substituted with halogen at the 4th position, Ar2 is phenyl, phenyl substituted with alkyl at the 4th position, phenyl substituted with alkoxy at the 4th position, phenyl substituted with halogen at the 4th position, phenyl substituted with phenyl at the 4th position or phenyl substituted with ester at the 4th position.

[0014] The beneficial effects of the present invention are:

[0015] The present invention develops a green, safe and stable alkylthio radical precursor reagent - alkylthiotriphenylphosphonium trifluoromethanesulfonate, uses alkylthiotriphenylphosphonium trifluoromethanesulfonate and 2-isocyanate-1,1'-biphenyl derivatives to form an active EDA complex, generates methylthio radicals under visible light irradiation, and realizes simple and efficient synthesis of alkyl thioether phenanthridine compounds without the participation of photocatalysts and transition metals. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 This is the H NMR spectrum of the alkyl sulfide phenanthridine prepared in Example 1;

[0017] Figure 2 This is the NMR carbon spectrum of the alkyl sulfide phenanthridine prepared in Example 1. DETAILED DESCRIPTION

[0018] Specific implementation method 1: This implementation method is a method for preparing an alkyl sulfide phenanthridine, which is carried out according to the following steps:

[0019] 1. mixing triphenylphosphine sulfide and trifluoromethanesulfonic acid alkyl reagent, and then adding an organic solvent to obtain a mixed solution I, reacting the mixed solution I at room temperature, and then removing the solvent and washing the solid to obtain alkylthiotriphenylphosphonium trifluoromethanesulfonate;

[0020] The molar ratio of triphenylphosphine sulfide to trifluoromethanesulfonic acid alkyl reagent is 1:(1-1.5);

[0021] The general structural formula of the alkylthiotriphenylphosphonium trifluoromethanesulfonate is Wherein R1 is methyl, ethyl, propyl or butyl;

[0022] 2. Under a nitrogen atmosphere, a 2-isocyanate-1,1'-biphenyl derivative and an alkylthiotriphenylphosphonium trifluoromethanesulfonate are mixed, and then an organic solvent is added to obtain a mixed solution II. Under a nitrogen atmosphere, the mixed solution II is irradiated with blue light for reaction, and then the solvent is removed and purified by chromatography to obtain an alkylthioether phenanthridine;

[0023] The molar ratio of the 2-isocyanate-1,1'-biphenyl derivative to the alkylthiotriphenylphosphonium trifluoromethanesulfonate is 1:(1.5-2);

[0024] The general structural formula of the 2-isocyanate-1,1'-biphenyl derivative is wherein Ar1 is phenyl, phenyl substituted with methyl at the 4th position or phenyl substituted with halogen at the 4th position, and Ar2 is phenyl, phenyl substituted with alkyl at the 4th position, phenyl substituted with alkoxy at the 4th position, phenyl substituted with halogen at the 4th position, phenyl substituted with phenyl at the 4th position or phenyl substituted with ester at the 4th position;

[0025] The structural formula of the alkyl sulfide phenanthridine is Wherein R1 is methyl, ethyl, propyl or butyl, Ar1 is phenyl, phenyl substituted with methyl at the 4th position or phenyl substituted with halogen at the 4th position, Ar2 is phenyl, phenyl substituted with alkyl at the 4th position, phenyl substituted with alkoxy at the 4th position, phenyl substituted with halogen at the 4th position, phenyl substituted with phenyl at the 4th position or phenyl substituted with ester at the 4th position.

[0026] The beneficial effects of this specific implementation are:

[0027] This specific implementation method develops a green, safe and stable alkylthio radical precursor reagent - alkylthiotriphenylphosphonium trifluoromethanesulfonate, and uses alkylthiotriphenylphosphonium trifluoromethanesulfonate to form an active EDA complex with a 2-isocyanate-1,1'-biphenyl derivative to generate methylthio radicals under visible light irradiation, thereby realizing a simple and efficient synthesis of alkyl thioether phenanthridine compounds without the participation of photocatalysts and transition metals.

[0028] Specific embodiment 2: This embodiment is different from specific embodiment 1 in that the trifluoromethanesulfonic acid alkyl reagent in step 1 is methyl trifluoromethanesulfonic acid, ethyl trifluoromethanesulfonic acid, propyl trifluoromethanesulfonic acid or butyl trifluoromethanesulfonic acid. The rest is the same as specific embodiment 1.

[0029] Specific embodiment 3: This embodiment differs from specific embodiment 1 or 2 in that the organic solvent in step 1 is dichloromethane, chloroform, N,N'-dimethylformamide or tetrahydrofuran. Others are the same as specific embodiment 1 or 2.

[0030] Specific embodiment 4: This embodiment is different from specific embodiments 1 to 3 in that the concentration of triphenylphosphine sulfide in the mixed solution I described in step 1 is 1 mol / L to 2 mol / L. Other aspects are the same as specific embodiments 1 to 3.

[0031] Specific embodiment 5: This embodiment differs from Specific embodiments 1 to 4 in that: in step 1, the mixed solution is reacted at room temperature for 10 h to 14 h. The rest is the same as Specific embodiments 1 to 4.

[0032] Specific embodiment 6: This embodiment is different from specific embodiments 1 to 5 in that the organic solvent in step 2 is N,N'-dimethylpropylene urea, N,N'-dimethylacetamide or N-methylpyrrolidone. The rest is the same as specific embodiments 1 to 5.

[0033] Specific embodiment 7: This embodiment differs from Specific embodiments 1 to 6 in that the concentration of the 2-isocyanate-1,1'-biphenyl derivative in the mixed solution II described in step 2 is 0.1 mol / L to 0.2 mol / L. The rest is the same as Specific embodiments 1 to 6.

[0034] Specific embodiment 8: This embodiment differs from specific embodiments 1 to 7 in that in step 2, the mixed solution II is irradiated with blue light for 10 to 14 hours under nitrogen atmosphere, room temperature, wavelength of 450nm and power of 10W to 15W. The rest is the same as specific embodiments 1 to 7.

[0035] Specific embodiment 9: This embodiment differs from specific embodiments 1 to 8 in that: in step 1, ether is used to wash the solid; in step 2, silica column chromatography is used for purification, and the eluent used for chromatography purification is a mixed solvent of n-hexane and ethyl acetate, and the volume ratio of n-hexane to ethyl acetate is (10-50):1. The rest is the same as specific embodiments 1 to 8.

[0036] Specific embodiment 10: This embodiment differs from any one of specific embodiments 1 to 9 in that the chemical reaction formula for preparing alkylthiotriphenylphosphonium trifluoromethanesulfonate in step 1 is:

[0037]

[0038] The chemical reaction formula for preparing alkyl sulfide phenanthridine in step 2 is:

[0039] The rest is the same as Specific Embodiments 1 to 9.

[0040] The following examples are used to verify the beneficial effects of the present invention:

[0041] Embodiment 1:

[0042] A method for preparing an alkyl sulfide phenanthridine is carried out according to the following steps:

[0043] 1. Triphenylphosphine sulfide (1 mmol, 294.4.0 mg, 1 equiv.) and trifluoromethanesulfonic acid alkyl reagent (1.1 mmol, 164.1 mg, 1.1 equiv.) were mixed, and then 1 mL of organic solvent was added to obtain a mixed solution I. The mixed solution I was reacted at room temperature for 12 h, and then the solvent was removed and the solid was washed with ether 3 times to obtain alkylthiotriphenylphosphonium trifluoromethanesulfonate;

[0044] The structural formula of the alkylthiotriphenylphosphonium trifluoromethanesulfonate is

[0045] 2. Under a nitrogen atmosphere, 2-isocyanate-1,1'-biphenyl derivative (1mmol, 179.2mg, 1.0equiv.) and alkylthiotriphenylphosphonium trifluoromethanesulfonate (1.5mmol, 687.7mg, 1.5equiv.) were mixed, and then 10mL of organic solvent was added to obtain a mixed solution II. Under a nitrogen atmosphere, room temperature, a wavelength of 450nm and a power of 15W, the mixed solution II was irradiated with blue light for 12h, and then the solvent was removed and purified by chromatography to obtain alkylthioether phenanthridine;

[0046] The structural formula of the 2-isocyanate-1,1'-biphenyl derivative is

[0047] The structural formula of the alkyl sulfide phenanthridine is

[0048] The trifluoromethanesulfonic acid alkyl reagent described in step 1 is methyl trifluoromethanesulfonate.

[0049] The organic solvent described in step 1 is dichloromethane.

[0050] The organic solvent described in step 2 is N,N'-dimethylpropylene urea.

[0051] In step 2, silica column chromatography is used for purification, and the eluent used for chromatography purification is a mixed solvent of n-hexane and ethyl acetate, and the volume ratio of n-hexane to ethyl acetate is 50:1.

[0052] The chemical reaction formula for preparing alkylthiotriphenylphosphonium trifluoromethanesulfonate in step 1 is:

[0053]

[0054] The chemical reaction formula for preparing alkyl sulfide phenanthridine in step 2 is:

[0055]

[0056] The alkyl sulfide phenanthridine prepared in Example 1 is a white solid with a yield of 86% and a purity of 96%.

[0057] Figure 1 This is the H NMR spectrum of the alkyl sulfide phenanthridine prepared in Example 1; Figure 2 The NMR carbon spectrum of the alkyl sulfide phenanthridine prepared in Example 1; The NMR characterization results of the alkyl sulfide phenanthridine prepared in Example 1: 1 H NMR (500MHz, CDCl3) δ = 8.55 (d, J = 11.1Hz, 1H), 8.46 (d, J = 8.1Hz, 1H), 8.31 (d, J = 8.1Hz, 1H), 8.0 3(d,J=8.2Hz,1H),7.84-7.77(m,1H),7.70-7.61(m,2H),7.58-7.51(m,1H),2.82-2.78(s,3H). 13 CNMR (126MHz, CDCl3) δ = 13.0, 122.3, 122.5, 122.8, 125.5, 125.7, 125.8, 127.5, 128.8, 128.9, 130.8, 132.1, 144.4, 160.1.

[0058] Example 2: This example is different from Example 1 in that the structural formula of the 2-isocyanate-1,1'-biphenyl derivative described in step 2 is In step 2, 2-isocyanate-1,1'-biphenyl derivative (1mmol, 209.3mg, 1.0equiv.) and alkylthiotriphenylphosphonium trifluoromethanesulfonate (1.5mmol, 687.7mg, 1.5equiv.) were mixed; the volume ratio of n-hexane to ethyl acetate in step 2 was 30:1; the structural formula of the alkylthioether phenanthridine in step 2 was The chemical reaction formula for preparing alkyl sulfide phenanthridine in step 2 is:

[0059] The rest is the same as that of the first embodiment.

[0060] The alkyl sulfide phenanthridine prepared in Example 2 is a white solid with a yield of 93% and a purity of 96%.

[0061] The NMR characterization results of the alkyl sulfide phenanthridine prepared in Example 2 are as follows: 1H NMR (500MHz, CDCl3) δ = 8.55 (d, J = 11.1Hz, 1H), 8.46 (d, J = 8.1Hz, 1H), 8.03 (d, J = 8.2Hz, 1H), 7 .84-7.77(m,1H),7.70-7.61(m,2H),7.58-7.51(m,1H),3.98-3.81(s,3H),2.82-2.78(s,3H). 13 C NMR (126MHz, CDCl3) δ = 13.0, 55.6, 122.3, 122.5, 122.8, 125.5, 125.7, 125.8, 127.5, 128.8, 128.9, 130.8, 132.1, 144.4, 160.1.

[0062] Example 3: This example is different from Example 1 in that the structural formula of the 2-isocyanate-1,1'-biphenyl derivative described in step 2 is In step 2, 2-isocyano-1,1'-biphenyl derivative (1 mmol, 193.3 mg, 1.0 equiv.) and alkylthiotriphenylphosphonium trifluoromethanesulfonate (1.5 mmol, 687.7 mg, 1.5 equiv.) are mixed; the structural formula of the alkylthioether phenanthridine in step 2 is The chemical reaction formula for preparing alkyl sulfide phenanthridine in step 2 is:

[0063] The rest is the same as that of the first embodiment.

[0064] The alkyl sulfide phenanthridine prepared in Example 3 is a white solid with a yield of 94% and a purity of 96%.

[0065] The NMR characterization results of the alkyl sulfide phenanthridine prepared in Example 3 are as follows: 1 H NMR (500MHz, CDCl3) δ = 8.41 (d, J = 8.3Hz, 2H), 8.07 (s, 1H), 8.01 (d, J = 7.9Hz, 1H), 7.67-7.57 (m, 2H), 7.56-7.48 (m, 1H), 2.80 (s, 3H), 2.57 (s, 3H). 13 C NMR (126MHz, CDCl3) δ = 159.6, 144.0, 137.5, 132.5, 129.8, 128.7, 128.4, 125.8, 125.7, 124.9, 122.9, 122.4, 122.1, 21.8, 13.0.

[0066] Example 4: This example is different from Example 1 in that the structural formula of the 2-isocyanate-1,1'-biphenyl derivative described in step 2 is In step 2, 2-isocyanate-1,1'-biphenyl derivative (1mmol, 258.1mg, 1.0equiv.) and alkylthiotriphenylphosphonium trifluoromethanesulfonate (1.5mmol, 687.7mg, 1.5equiv.) were mixed; the volume ratio of n-hexane to ethyl acetate in step 2 was 20:1; the structural formula of the alkylthioether phenanthridine in step 2 was The chemical reaction formula for preparing alkyl sulfide phenanthridine in step 2 is:

[0067] The rest is the same as that of the first embodiment.

[0068] The alkyl sulfide phenanthridine prepared in Example 4 is a white solid with a yield of 93% and a purity of 97%.

[0069] The NMR characterization results of the alkyl sulfide phenanthridine prepared in Example 4 are as follows: 1 H NMR (500MHz, CDCl3) δ = 8.46-8.37 (m, 3H), 8.02 (d, J = 8.3Hz, 1H), 7.92-7.85 (m, 1H), 7.73-7.64 (m, 1H), 7.60-7.51 (m, 1H), 2.80 (s, 3H). 13 C NMR (126MHz, CDCl3) δ = 158.9, 144.3, 134.03, 129.3, 129.0, 128.1, 126.2, 124.4, 122.2, 122.1, 13.1.

[0070] Example 5: This example is different from Example 1 in that the structural formula of the 2-isocyanate-1,1'-biphenyl derivative described in step 2 is In step 2, 2-isocyanate-1,1'-biphenyl derivative (1mmol, 255.3mg, 1.0equiv.) and alkylthiotriphenylphosphonium trifluoromethanesulfonate (1.5mmol, 687.7mg, 1.5equiv.) were mixed; the volume ratio of n-hexane to ethyl acetate in step 2 was 30:1; the structural formula of the alkylthioether phenanthridine in step 2 was The chemical reaction formula for preparing alkyl sulfide phenanthridine in step 2 is:

[0071] The rest is the same as that of the first embodiment.

[0072] The alkyl sulfide phenanthridine prepared in Example 5 is a white solid with a yield of 82% and a purity of 96%.

[0073] The NMR characterization results of the alkyl sulfide phenanthridine prepared in Example 5 are as follows: 1H NMR (500MHz, CDCl3) δ = 8.52 (d, J = 10.5Hz, 1H), 8.46 (s, 1H), 8.41 (d, J = 8.2Hz, 1H), 8.04-7.96 (m, 2H),7.72(d,J=8.2Hz,2H),7.69-7.60(m,1H),7.56-7.46(m,3H),7.43-7.37(m,1H),2.80(s,3H). 13 C NMR (126MHz, CDCl3) δ=160.1,144.3,140.3,140.2,131.0,129.9,129.1,128.8,128.0,127.6,126.1,125.8,123.4,123.0,122.6,122.3,13.0.

[0074] Example 6: This example is different from Example 1 in that the structural formula of the 2-isocyanate-1,1'-biphenyl derivative described in step 2 is In step 2, 2-isocyanate-1,1'-biphenyl derivative (1mmol, 237.3mg, 1.0equiv.) and alkylthiotriphenylphosphonium trifluoromethanesulfonate (1.5mmol, 687.7mg, 1.5equiv.) were mixed; the volume ratio of n-hexane to ethyl acetate in step 2 was 20:1; the structural formula of the alkylthioether phenanthridine in step 2 was The chemical reaction formula for preparing alkyl sulfide phenanthridine in step 2 is:

[0075]

[0076] The rest is the same as that of the first embodiment.

[0077] The alkyl sulfide phenanthridine prepared in Example 6 is a white solid with a yield of 96% and a purity of 96%.

[0078] The NMR characterization results of the alkyl sulfide phenanthridine prepared in Example 6 are as follows: 1 H NMR(500MHz,Chloroform-d)δ9.00(s,1H),8.59(d,J=8.7Hz,1H),8.48(d,J=8.1Hz,1H),8.41(d,J= 8.5,1.6Hz,1H),8.09-7.99(m,1H),7.80-7.68(m,1H),7.62-7.52(m,1H),4.02(s,3H),2.81(s,3H). 13CNMR(151MHz,Chloroform-d)δ166.5,160.7,145.1,135.3,130.7,130.1,129.0,128.9,127.6,126.1,125.3,122.9,122.8,122.1,52.7,13.1.

[0079] Example 7: This example is different from Example 1 in that the structural formula of the 2-isocyanate-1,1'-biphenyl derivative described in step 2 is In step 2, under a nitrogen atmosphere, 2-isocyanate-1,1'-biphenyl derivative (1mmol, 193.3mg, 1.0equiv.) and alkylthiotriphenylphosphonium trifluoromethanesulfonate (2mmol, 916.9mg, 2equiv.) are mixed, and then 5mL of organic solvent is added to obtain a mixed solution II. Under a nitrogen atmosphere, room temperature, a wavelength of 450nm and a power of 15W, the mixed solution II is irradiated with blue light for 14h, and then the solvent is removed and purified by chromatography to obtain an alkyl thioether phenanthridine; the organic solvent described in step 2 is N-methylpyrrolidone; the structural formula of the alkyl thioether phenanthridine described in step 2 is The chemical reaction formula for preparing alkyl sulfide phenanthridine in step 2 is:

[0080] The rest is the same as that of the first embodiment.

[0081] The alkyl sulfide phenanthridine prepared in Example 7 is a white solid with a yield of 93% and a purity of 96%.

[0082] The NMR characterization results of the alkyl sulfide phenanthridine prepared in Example 7 are as follows: 1 H NMR (500MHz, CDCl3) δ = 8.49 (d, J = 8.3Hz, 1H), 8.33 (d, J = 8.3Hz, 1H), 8.28 (d, J = 8.2Hz, 1H), 7.83 (s,1H),7.80-7.73(m,1H),7.67-7.55(m,1H),7.36(d,J=10.1Hz,1H),2.79(s,3H),2.56(s,3H). 13 C NMR (126MHz, CDCl3) δ = 160.0, 144.4, 139.0, 132.2, 130.7, 128.5, 127.4, 127.0, 125.4, 122.3, 122.1, 120.4, 21.6, 13.0.

[0083] Example 8: This example is different from Example 1 in that the structural formula of the 2-isocyanate-1,1'-biphenyl derivative described in step 2 is In step 2, under a nitrogen atmosphere, 2-isocyanate-1,1'-biphenyl derivative (1mmol, 197.2mg, 1.0equiv.) and alkylthiotriphenylphosphonium trifluoromethanesulfonate (2mmol, 916.9mg, 2equiv.) are mixed, and then 5mL of organic solvent is added to obtain a mixed solution II. Under a nitrogen atmosphere, room temperature, a wavelength of 450nm and a power of 15W, the mixed solution II is irradiated with blue light for 14h, and then the solvent is removed and purified by chromatography to obtain an alkyl thioether phenanthridine; the organic solvent described in step 2 is N-methylpyrrolidone; the volume ratio of n-hexane to ethyl acetate described in step 2 is 20:1; the structural formula of the alkyl thioether phenanthridine described in step 2 is The chemical reaction formula for preparing alkyl sulfide phenanthridine in step 2 is:

[0084] The rest is the same as that of the first embodiment.

[0085] The alkyl sulfide phenanthridine prepared in Example 8 is a white solid with a yield of 91% and a purity of 96%.

[0086] The NMR characterization results of the alkyl sulfide phenanthridine prepared in Example 8 are as follows: 1 H NMR (500MHz, CDCl3) δ = 8.43 (d, J = 8.3Hz, 1H), 8.36-8.28 (m, 1H), 8.08-8.05 (m, 1H), 8.01 (d d,J=8.4,6.2Hz,1H),7.85-7.81(m,1H),7.72-7.67(m,1H),7.43-7.36(m,1H),2.79(s,3H). 13 C NMR (126MHz, CDCl3) δ = 160.6 (d, J = 245.0Hz), 159.4, 141.2, 131.5, 130.9, 130.8 (d, J = 9.4Hz), 1 28.1, 125.7, 125.5, 124.0 (d, J = 8.8Hz), 122.6, 117.4 (d, J = 24.1Hz), 107.3 (d, J = 23.2Hz), 13.0. 19 F NMR (471MHz, CDCl3) δ = -108.34--107.42 (m, 1F).

[0087] Embodiment nine:

[0088] A method for preparing an alkyl sulfide phenanthridine is carried out according to the following steps:

[0089] 1. Triphenylphosphine sulfide (1 mmol, 294.4.0 mg, 1 equiv.) and trifluoromethanesulfonic acid alkyl reagent (1.5 mmol, 267.1 mg, 1.5 equiv.) were mixed, and then 0.5 mL of organic solvent was added to obtain a mixed solution I. The mixed solution I was reacted at room temperature for 12 h, and then the solvent was removed and the solid was washed with ether 3 times to obtain alkylthiotriphenylphosphonium trifluoromethanesulfonate with a purity of 96%;

[0090] The structural formula of the alkylthiotriphenylphosphonium trifluoromethanesulfonate is

[0091] 2. Under a nitrogen atmosphere, 2-isocyanate-1,1'-biphenyl derivative (1mmol, 209.3mg, 1.0equiv.) and alkylthiotriphenylphosphonium trifluoromethanesulfonate (2mmol, 945.1mg, 2equiv.) were mixed, and then 5mL of organic solvent was added to obtain a mixed solution II. Under a nitrogen atmosphere, room temperature, a wavelength of 450nm and a power of 15W, the mixed solution II was irradiated with blue light for 14h, and then the solvent was removed and purified by chromatography to obtain alkylthioether phenanthridine;

[0092] The structural formula of the 2-isocyanate-1,1'-biphenyl derivative is

[0093] The structural formula of the alkyl sulfide phenanthridine is

[0094] The trifluoromethanesulfonic acid alkyl reagent described in step 1 is ethyl trifluoromethanesulfonate.

[0095] The organic solvent described in step 1 is dichloromethane.

[0096] The organic solvent described in step 2 is N,N'-dimethylacetamide.

[0097] In step 2, silica column chromatography is used for purification, and the eluent used for chromatography purification is a mixed solvent of n-hexane and ethyl acetate, and the volume ratio of n-hexane to ethyl acetate is 20:1.

[0098] The chemical reaction formula for preparing alkylthiotriphenylphosphonium trifluoromethanesulfonate in step 1 is:

[0099]

[0100] The chemical reaction formula for preparing alkyl sulfide phenanthridine in step 2 is:

[0101]

[0102] The alkyl sulfide phenanthridine prepared in Example 9 is a white solid with a yield of 92% and a purity of 96%.

[0103] The NMR characterization results of the alkyl sulfide phenanthridine prepared in Example 9 are as follows: 1 H NMR (500MHz, CDCl3) δ = 8.45 (d, J = 9.0Hz, 1H), 8.37 (d, J = 9.5Hz, 1H), 7.98 (d, J = 9.5Hz, 1H), 7.62-7.57 (m, 2H ),7.54-7.48(m,1H),7.42(dd,J=9.0,2.6Hz,1H),3.98(s,3H),3.48(q,J=7.4Hz,2H),1.50(t,J=7.4Hz,3H). 13 CNMR (126MHz, CDCl3) δ = 158.8, 158.4, 143.5, 128.8, 127.8, 127.0, 126.3, 125.7, 124.1, 122.9, 121.7, 121.4, 105.5, 55.7, 24.3, 14.7.

[0104] Embodiment ten:

[0105] A method for preparing an alkyl sulfide phenanthridine is carried out according to the following steps:

[0106] 1. Triphenylphosphine sulfide (1 mmol, 294.4.0 mg, 1 equiv.) and trifluoromethanesulfonic acid alkyl reagent (1.5 mmol, 288.3 mg, 1.1 equiv.) were mixed, and then 0.5 mL of organic solvent was added to obtain a mixed solution I. The mixed solution I was reacted at room temperature for 12 h, and then the solvent was removed and the solid was washed with ether 3 times to obtain alkylthiotriphenylphosphonium trifluoromethanesulfonate with a purity of 96%;

[0107] The structural formula of the alkylthiotriphenylphosphonium trifluoromethanesulfonate is

[0108] 2. Under a nitrogen atmosphere, 2-isocyanate-1,1'-biphenyl derivative (1mmol, 209.3mg, 1.0equiv.) and alkylthiotriphenylphosphonium trifluoromethanesulfonate (2mmol, 973.1mg, 2equiv.) were mixed, and then 5mL of organic solvent was added to obtain a mixed solution II. Under a nitrogen atmosphere, room temperature, a wavelength of 450nm and a power of 15W, the mixed solution II was irradiated with blue light for 14h, and then the solvent was removed and purified by chromatography to obtain alkylthioether phenanthridine;

[0109] The structural formula of the 2-isocyanate-1,1'-biphenyl derivative is

[0110] The structural formula of the alkyl sulfide phenanthridine is

[0111] The trifluoromethanesulfonic acid alkyl reagent described in step 1 is isopropyl trifluoromethanesulfonate.

[0112] The organic solvent described in step 1 is dichloromethane.

[0113] The organic solvent described in step 2 is N,N'-dimethylacetamide.

[0114] In step 2, silica column chromatography is used for purification, and the eluent used for chromatography purification is a mixed solvent of n-hexane and ethyl acetate, and the volume ratio of n-hexane to ethyl acetate is 30:1.

[0115] The chemical reaction formula for preparing alkylthiotriphenylphosphonium trifluoromethanesulfonate in step 1 is:

[0116]

[0117] The chemical reaction formula for preparing alkyl sulfide phenanthridine in step 2 is:

[0118]

[0119] The alkyl sulfide phenanthridine prepared in Example 10 is a white solid with a yield of 88% and a purity of 97%.

[0120] The NMR characterization results of the alkyl sulfide phenanthridine prepared in Example 10 are as follows: 1 H NMR (500MHz, CDCl3) δ = 8.46 (d, J = 9.0Hz, 1H), 8.38 (d, J = 9.6Hz, 1H), 7.99 (d, J = 9.4Hz, 1H), 7.65-7.58 (m, 2H), 7.55 -7.49(m,1H),7.43(dd,J=9.0,2.6Hz,1H),3.99(s,3H),3.07(t,J=7.3Hz,1H),1.31(d,6H),1.13(t,J=7.4Hz,3H). 13 C NMR (126MHz, CDCl3) δ = 160.4, 158.3, 143.1, 134.5, 129.9, 128.9, 127.9, 126.1, 124.3, 122.7, 122.4, 118.6, 107.7, 58.2, 31.4, 22.3.

[0121] Embodiment eleven:

[0122] A method for preparing an alkyl sulfide phenanthridine is carried out according to the following steps:

[0123] 1. Triphenylphosphine sulfide (1 mmol, 294.4.0 mg, 1 equiv.) and trifluoromethanesulfonic acid alkyl reagent (1.5 mmol, 309.3 mg, 1.5 equiv.) were mixed, and then 0.5 mL of organic solvent was added to obtain a mixed solution I. The mixed solution I was reacted at room temperature for 14 h, and then the solvent was removed and the solid was washed with ether 3 times to obtain alkylthiotriphenylphosphonium trifluoromethanesulfonate with a purity of 96%;

[0124] The structural formula of the alkylthiotriphenylphosphonium trifluoromethanesulfonate is

[0125] 2. Under a nitrogen atmosphere, 2-isocyanate-1,1'-biphenyl derivative (1mmol, 209.3mg, 1.0equiv.) and alkylthiotriphenylphosphonium trifluoromethanesulfonate (2mmol, 1001.1mg, 2equiv.) were mixed, and then 5mL of organic solvent was added to obtain a mixed solution II. Under a nitrogen atmosphere, room temperature, a wavelength of 450nm and a power of 15W, the mixed solution II was irradiated with blue light for 14h, and then the solvent was removed and purified by chromatography to obtain alkylthioether phenanthridine;

[0126] The structural formula of the 2-isocyanate-1,1'-biphenyl derivative is

[0127] The structural formula of the alkyl sulfide phenanthridine is

[0128] The trifluorosulfonic acid alkyl reagent described in step 1 is n-butyl trifluoromethanesulfonate.

[0129] The organic solvent described in step 1 is dichloromethane.

[0130] The organic solvent described in step 2 is N,N'-dimethylacetamide.

[0131] In step 2, silica column chromatography is used for purification, and the eluent used for chromatography purification is a mixed solvent of n-hexane and ethyl acetate, and the volume ratio of n-hexane to ethyl acetate is 30:1.

[0132] The chemical reaction formula for preparing alkylthiotriphenylphosphonium trifluoromethanesulfonate in step 1 is:

[0133]

[0134] The chemical reaction formula for preparing alkyl sulfide phenanthridine in step 2 is:

[0135]

[0136] The alkyl sulfide phenanthridine prepared in Example 11 is a white solid with a yield of 84% and a purity of 97%.

[0137] The NMR characterization results of the alkyl sulfide phenanthridine prepared in Example 11 are as follows: 1 H NMR(500MHz, CDCl3)δ=8.45(d,J=9.1Hz,1H),8.37(d,J=8.1Hz,1H),7.99(d,J=8.2Hz,1H),7.64-7.57(m,2H),7.54-7.49(m,1 H),7.43-7.39(m,1H),3.98(d,J=1.4Hz,3H),3.49(td,J=7.4,1.3Hz,2H),1.87-1.79(m,2H),1.61-1.53(m,2H),1.00(t,3H). 13 C NMR (126MHz, CDCl3) δ = 158.8, 158.6, 143.4, 128.7, 127.8, 127.0, 126.3, 125 .7,124.1,122.9,121.7,121.4,105.4,55.7,55.4,31.6,29.6,22.4,13.9..

[0138] Example 12: This example differs from Example 1 in that: in step 1, the reaction is carried out at room temperature for 10 hours; in step 2, the mixed solution II is irradiated with blue light for 10 hours under nitrogen atmosphere, room temperature, wavelength of 450nm and power of 15W. The rest is the same as Example 1.

[0139] The alkyl sulfide phenanthridine prepared in Example 12 is a white solid with a yield of 81 and a purity of 96%.

[0140] The NMR characterization results of the alkyl sulfide phenanthridine prepared in Example 12 are as follows: 1 H NMR (500MHz, CDCl3) δ = 8.55 (d, J = 11.1Hz, 1H), 8.46 (d, J = 8.1Hz, 1H), 8.31 (d, J = 8.1Hz, 1H), 8.0 3(d,J=8.2Hz,1H),7.84-7.77(m,1H),7.70-7.61(m,2H),7.58-7.51(m,1H),2.82-2.78(s,3H). 13 C

[0141] NMR (126MHz, CDCl3) δ = 13.0, 122.3, 122.5, 122.8, 125.5, 125.7, 125.8, 127.5, 128.

[0142] 8,128.9,130.8,132.1,144.4,160.1.

Claims

1. A method for preparing an alkyl sulfide phenanthridine, characterized in that It is carried out in the following steps:

1. mixing triphenylphosphine sulfide and trifluoromethanesulfonic acid alkyl reagent, and then adding an organic solvent to obtain a mixed solution I, reacting the mixed solution I at room temperature, and then removing the solvent and washing the solid to obtain alkylthiotriphenylphosphonium trifluoromethanesulfonate; The molar ratio of triphenylphosphine sulfide to trifluoromethanesulfonic acid alkyl reagent is 1:(1-1.5); The general structural formula of the alkylthiotriphenylphosphonium trifluoromethanesulfonate is Wherein R1 is methyl, ethyl, propyl or butyl; 2. Under a nitrogen atmosphere, a 2-isocyanate-1,1'-biphenyl derivative and an alkylthiotriphenylphosphonium trifluoromethanesulfonate are mixed, and then an organic solvent is added to obtain a mixed solution II. Under a nitrogen atmosphere, the mixed solution II is irradiated with blue light for reaction, and then the solvent is removed and purified by chromatography to obtain an alkylthioether phenanthridine; The molar ratio of the 2-isocyanate-1,1'-biphenyl derivative to the alkylthiotriphenylphosphonium trifluoromethanesulfonate is 1:(1.5-2); The general structural formula of the 2-isocyanate-1,1'-biphenyl derivative is wherein Ar1 is phenyl, phenyl substituted with methyl at the 4th position or phenyl substituted with halogen at the 4th position, and Ar2 is phenyl, phenyl substituted with alkyl at the 4th position, phenyl substituted with alkoxy at the 4th position, phenyl substituted with halogen at the 4th position, phenyl substituted with phenyl at the 4th position or phenyl substituted with ester at the 4th position; The structural formula of the alkyl sulfide phenanthridine is Wherein R1 is methyl, ethyl, propyl or butyl, Ar1 is phenyl, phenyl substituted with methyl at the 4th position or phenyl substituted with halogen at the 4th position, Ar2 is phenyl, phenyl substituted with alkyl at the 4th position, phenyl substituted with alkoxy at the 4th position, phenyl substituted with halogen at the 4th position, phenyl substituted with phenyl at the 4th position or phenyl substituted with ester at the 4th position.

2. The method for preparing an alkyl sulfide phenanthridine according to claim 1, wherein The trifluoromethanesulfonic acid alkyl reagent described in step 1 is methyltrifluoromethanesulfonic acid, ethyltrifluoromethanesulfonic acid, propyltrifluoromethanesulfonic acid or butyltrifluoromethanesulfonic acid.

3. The method for preparing an alkyl sulfide phenanthridine according to claim 1, wherein The organic solvent in step 1 is dichloromethane, chloroform, N,N'-dimethylformamide or tetrahydrofuran.

4. The method for preparing an alkyl sulfide phenanthridine according to claim 1, wherein The concentration of triphenylphosphine sulfide in the mixed solution I described in step 1 is 1 mol / L to 2 mol / L.

5. The method for preparing an alkyl sulfide phenanthridine according to claim 1, wherein In step 1, the mixed solution is reacted at room temperature for 10 h to 14 h.

6. The method for preparing an alkyl sulfide phenanthridine according to claim 1, wherein The organic solvent in step 2 is N,N'-dimethylpropylene urea, N,N'-dimethylacetamide or N-methylpyrrolidone.

7. The method for preparing an alkyl sulfide phenanthridine according to claim 1, characterized in that The concentration of the 2-isocyanate-1,1'-biphenyl derivative in the mixed solution II described in step 2 is 0.1 mol / L to 0.2 mol / L.

8. The method for preparing an alkyl sulfide phenanthridine according to claim 1, characterized in that In step 2, the mixed solution II is irradiated with blue light for 10 h to 14 h under the conditions of nitrogen atmosphere, room temperature, wavelength of 450 nm and power of 10 W to 15 W.

9. The method for preparing an alkyl sulfide phenanthridine according to claim 1, wherein In step 1, the solid is washed with ether; in step 2, silica column chromatography is used for purification, and the eluent used for chromatography purification is a mixed solvent of n-hexane and ethyl acetate, and the volume ratio of n-hexane to ethyl acetate is (10-50):

1.

10. The method for preparing an alkyl sulfide phenanthridine according to claim 1, characterized in that The chemical reaction formula for preparing alkylthiotriphenylphosphonium trifluoromethanesulfonate in step 1 is: The chemical reaction formula for preparing alkyl sulfide phenanthridine in step 2 is:

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