Method for preparing alkyl phosphorothioate through direct functionalization of C-H bond

Abstract

The invention discloses a method for preparing alkyl phosphorothioate through direct functionalization of a C-H bond, and belongs to the technical field of organic synthesis. The method comprises the following steps: adding a compound 1, a P (O) SH compound 2a, a photocatalyst, a copper catalyst and an oxidizing agent into a solvent, reacting in a protective atmosphere and under the irradiation of visible light, and after the reaction is completed, performing post-treatment to obtain the alkyl thiophosphate. The method for synthesizing the alkyl phosphorothioate through direct sulfur and phosphorus esterification of the C-H bond is a simple and efficient synthesis method. The method does not need to functionalize the raw materials in advance, greatly enriches product diversity, and has the characteristics of few steps, atom economy, simple operation and the like.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, and particularly relates to a method for preparing alkyl thiophosphates by direct functionalization via CH bonds. Background Technology

[0002] Alkyl thiophosphates are a class of organophosphorus compounds with unique biological activities and physicochemical properties, showing great application potential in agriculture, medicine, and other fields. For example, the core skeleton of commercially available crop protectants, low-toxicity herbicides and insecticides, and drugs used in the medical field to treat cancer, glaucoma, and heart failure are all alkyl thiophosphates. Traditional synthetic methods mainly involve the construction of PS bonds, such as the nucleophilic substitution reaction of thiols with phosphoryl halides, the nucleophilic reaction of thiohalides with H-phosphites P(O)H, and the dehydrogenation coupling reaction of (RO)₂P(O)H with thiophenols, thiols, etc. However, these reactions require highly toxic and irritating raw materials, require harsh reaction conditions, and have limited substrate availability.

[0003] To address the problems of the traditional synthetic methods mentioned above, the synthesis of alkyl thiophosphates via CS bond construction using (RO)₂P(O)SH as a raw material has attracted considerable attention. Currently, methods for synthesizing alkyl thiophosphates via CS bond construction include: (1) nucleophilic substitution reactions of (RO)₂P(O)SH with halogenated hydrocarbons, alcohols, etc.; (2) photocatalytic decarboxylation coupling reactions of (RO)₂P(O)SH with activated carboxylic acid esters; and (3) long-range C(sp) bonding reactions of sulfonamides or N-alkoxypyridinium salts. 3 (4) Addition reaction of (RO)2P(O)SH with olefins or bifunctionalization reaction. However, the above methods still have disadvantages such as complex substrate synthesis, need for pre-activation of substrates and limited substrate diversity. Therefore, it is urgent to develop a method for synthesizing alkyl thiophosphates with fewer steps and atom economy. Summary of the Invention

[0004] To address the aforementioned technical problems, this invention proposes a method for preparing alkyl thiophosphates via direct functionalization of CH bonds.

[0005] To achieve the above objectives, the present invention provides the following technical solution:

[0006] This invention provides a method for preparing alkyl thiophosphates via direct functionalization of CH bonds, comprising the following steps: adding compound 1, P(O)SH compound 2a, a photocatalyst, a copper catalyst, and an oxidant to a solvent, reacting under a protective atmosphere and visible light irradiation, and obtaining the alkyl thiophosphates after post-treatment following complete reaction; wherein, the structural formula of compound 1 is as follows: The structural formula of the P(O)SH compound 2a is as follows: The structural formula of the alkyl thiophosphate is as follows: R is selected from H, aryl, or alkyl.

[0007] Furthermore, the reaction equation for the preparation process is as follows: .

[0008] Further, the molar ratio of compound 1, P(O)SH compound 2a, photocatalyst, copper catalyst and oxidant is 1∶(2-4):(0.01-0.05):(0.1-0.2):(2-3), preferably 1∶2∶0.02∶0.1∶2.

[0009] Furthermore, the photocatalyst is selected from 2,4,5,6-tetra(9H-carbazole-9-yl)isophthalonitrile (4CzIPN) and / or Ensoin Y, preferably 2,4,5,6-tetra(9H-carbazole-9-yl)isophthalonitrile (4CzIPN).

[0010] Furthermore, the copper catalyst is selected from at least one of CuSO4, Cu(OAc)2, Cu2O, CuBr2, CuO, CuCl and CuBr, preferably at least one of CuSO4, Cu(OAc)2 and CuBr, and more preferably CuSO4.

[0011] Further, the oxidant is selected from at least one of K2S2O8, tert-butyl hydroperoxide (TBHP) and tert-butyl perbenzoate (TBPB), preferably K2S2O8.

[0012] Furthermore, the solvent is a mixed solution of water and an organic solvent; the organic solvent is selected from acetonitrile (MeCN).

[0013] Furthermore, the ratio of water, organic solvent, and compound 1 is 0.2-0.5 mmol: 1-3 mL: 0.2 mmol.

[0014] Furthermore, the visible light is blue light; the power of the blue light is 6-32W.

[0015] Furthermore, the reaction temperature is room temperature, and the reaction time is 4-24 hours.

[0016] Furthermore, the post-processing includes reduced pressure concentration and purification by silica gel column chromatography; the eluent for purification is petroleum ether and ethyl acetate, wherein the volume ratio of petroleum ether to ethyl acetate is 3:1.

[0017] Furthermore, the structural formula of the alkyl thiophosphate is as follows: , , , , , , , , , , , , , , , , , , , , , or .

[0018] Compared with the prior art, the present invention has the following advantages and technical effects:

[0019] The method for synthesizing alkyl thiophosphates via direct thiophosphorylation through CH bonds provided by this invention is a simple and efficient synthetic method. This method eliminates the need for pre-functionalization of the starting materials, greatly enriches product diversity, and features fewer steps, atom economy, and simple operation. Attached Figure Description

[0020] The accompanying drawings, which form part of this invention, are used to provide a further understanding of the invention. The illustrative embodiments of the invention and their descriptions are used to explain the invention and do not constitute an undue limitation of the invention. In the drawings:

[0021] Figure 1 For compound 3 in CDCl3 1 1H NMR (400MHz) spectrum;

[0022] Figure 2 For compound 3 in CDCl3 13 C NMR (400MHz) spectrum;

[0023] Figure 3 For compound 3 in CDCl3 31 P NMR (400MHz) spectrum;

[0024] Figure 4 For compound 4 in CDCl3 1 1H NMR (400MHz) spectrum;

[0025] Figure 5 For compound 4 in CDCl3 13 C NMR (400MHz) spectrum;

[0026] Figure 6For compound 4 in CDCl3 31 P NMR (400MHz) spectrum. Detailed Implementation

[0027] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0028] To make the above-mentioned objects, features and advantages of the present invention more apparent and understandable, the present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments.

[0029] In this embodiment of the invention, room temperature refers to "25±2℃".

[0030] Unless otherwise specified, all raw materials used in the embodiments of this invention were purchased through commercial channels.

[0031] Example 1

[0032] A method for preparing alkyl thiophosphates via direct functionalization of CH bonds comprises the following steps: a copper catalyst (0.02 mmol, 10 mol%), a photocatalyst (0.004 mmol, 2 mol%), and an oxidant (0.4 mmol, 2.0 equivalent) are placed in a dry reaction tube, which is subjected to three vacuum cycles followed by argon circulation. Then, under argon protection, compound 1a (0.2 mmol, 1.0 equivalent), P(O)SH compound 2a (0.4 mmol, 2.0 equivalent), H2O (0.2 mmol, 1.0 equivalent), and an organic solvent (3 mL) are added. The reaction is then stirred at room temperature for 24 hours under 15 W blue LED illumination. After the reaction, the mixture is concentrated under reduced pressure, and the residue is purified by silica gel column chromatography (eluent: petroleum ether and ethyl acetate, volume ratio 3:1) to obtain compound 3.

[0033] The reaction equation for the preparation process is as follows: ;

[0034] The specific types of photocatalysts, copper catalysts, oxidants, and organic solvents are shown in Table 1.

[0035] Table 1

[0036]

[0037] Note: aReaction conditions: 1a (0.2 mmol), 2a (0.4 mmol, 2.0 equiv), photocatalyst (2 mol%), copper catalyst (0.02 mmol, 10 mol%), oxidant (0.4 mmol, 2.0 equiv), H₂O (1.0 equiv), organic solvent (3 mL), 15W blue LED, Ar, room temperature, 24 h. Yield was determined by using triphenyl phosphate as an internal standard. 31 P nuclear magnetic resonance measurement. b The values ​​in parentheses represent the yields of the separated products. c Under light-protected conditions. 4CzIPN: 2,4,5,6-Tetra(9H-carbazole-9-yl)isophthalonitrile; Ir[(ppy)2dtbpy]PF6: (4,4'-di-tert-butyl-2,2'-bipyridine)bis[(2-pyridyl)phenyl]iridium(III)hexafluorophosphate; Ru(bpy)3Cl2: tris(2,2'-bipyridine)ruthenium dichloride; NFSI: N-fluorobis(benzenesulfonamide); DTBP: di-tert-butyl peroxide; DCM: dichloromethane; EtOH: ethanol; 1,4-dioxane: 1,4-dioxane; Toluene: toluene; DMF: N,N-dimethylformamide; DMSO: dimethyl sulfoxide. Trace: trace amount.

[0038] As shown in Table 1, the optimal reaction conditions for the preparation of alkyl thiophosphates via direct functionalization of CH bonds are: 4CzIPN as the photocatalyst, CuSO4 as the copper catalyst, K2S2O8 as the oxidant, and MeCN as the organic solvent.

[0039] Compound 3 prepared in Example 1 is O,O,O',O'-tetraethyl S,S'-(2-oxo-1-phenylindoline-3,3-diyl)bis(phosphorothioate), a yellow liquid with the following structural formula: The yield of compound 3 obtained under optimal reaction conditions 4 was 58.1 mg, or 83%.

[0040] Compound 3 in CDCl3 1 The H NMR (400MHz) spectrum is shown below. Figure 1 Compound 3 in CDCl3 13 The C NMR (400MHz) spectrum is shown below. Figure 2 Compound 3 in CDCl3 31 The P NMR (400MHz) spectrum is shown below. Figure 3 .

[0041] NMR data of compound 3: 1 H NMR (400 MHz, CDCl3) δ 7.59 – 7.55 (m, 4H),7.49 – 7.40 (m, 4H), 7.35 (t, J = 7.3 Hz, 1H), 4.59 – 4.51 (m, 1H), 4.18 –3.88 (m, 4H), 1.79 (d, J = 7.1 Hz, 3H), 1.27 – 1.23 (m, 6H). 13 C NMR (101 MHz, CDCl3) δ 142.7 (d, J = 5.1 Hz), 140.8, 140.7, 129.0, 127.6, 127.55, 127.5,127.2, 63.6 (d, J = 1.8 Hz), 63.5 (d, J = 1.6 Hz), 45.7 (d, J = 3.6 Hz), 24.7(d, J = 7.6 Hz), 16.1 (d, J = 1.5 Hz), 16.0 (d, J = 1.4 Hz). 31 P NMR (162 MHz, CDCl3) δ 25.90. HRMS: [M+Na] + m / z calcd for C 18 H 23 NaO3PS + : 373.0998, found:373.0995.

[0042] Example 2

[0043] A method for preparing alkyl thiophosphates via direct functionalization of CH bonds comprises the following steps: CuSO4·5H2O (0.02 mmol, 10 mol%), 4CzIPN (0.004 mmol, 2 mol%), and K2S2O8 (0.4 mmol, 2.0 equivalents) are placed in a dry reaction tube, which is subjected to three vacuum cycles followed by argon circulation. Then, under argon protection, compound 1 (0.2 mmol, 1.0 equivalents), P(O)SH compound 2a (0.4 mmol, 2.0 equivalents), H2O (0.2 mmol, 1.0 equivalents), and acetonitrile (3 mL) are added. The reaction is stirred at room temperature for 24 hours under 15W blue LED illumination. After the reaction, the mixture is concentrated under reduced pressure, and the residue is purified by silica gel column chromatography (eluent: petroleum ether and ethyl acetate, volume ratio 3:1) to obtain compound 4-25.

[0044] The reaction equation for the preparation process is as follows:

[0045] Where R = H, aryl or alkyl;

[0046] The structural formula of compound 1 used to prepare compound 4-25 is shown in Table 2.

[0047] Table 2

[0048]

[0049] The data for compound 4-25 are as follows:

[0050] Compound 4: O,O,O',O'-Tetraethyl S,S'-(2-oxo-1-phenylindoline-3,3-diyl)bis(phosphorothioate) (O,O,O',O'-Tetraethyl S,S'-(2-oxo-1-phenylindoline-3,3-diyl)bis(phosphorothioate)), yield: 28.0 mg, 51%, yellow liquid; structural formula: .

[0051] Compound 4 in CDCl3 1 The H NMR (400MHz) spectrum is shown below. Figure 4 Compound 4 in CDCl3 13 The C NMR (400MHz) spectrum is shown below. Figure 5 Compound 4 in CDCl3 31 The P NMR (400MHz) spectrum is shown below. Figure 6 .

[0052] NMR data of compound 4: 1 H NMR (400 MHz, CDCl3) δ 7.40 – 7.36 (m, 2H),7.35 – 7.30 (m, 2H), 7.28 – 7.23 (m, 1H), 4.53 – 4.44 (m, 1H), 4.16 – 3.84(m, 4H), 1.75 (dd, J = 7.2, 1.1 Hz, 3H), 1.24 (dt, J = 7.1, 0.9 Hz, 6H). 13 CNMR (101 MHz, CDCl3) δ 143.7 (d, J = 5.0 Hz), 128.8, 127.8, 127.2, 63.6 (d, J= 1.5 Hz), 63.6 (d, J = 1.5 Hz), 46.0 (d, J = 3.5 Hz), 24.8 (d, J = 7.6 Hz), 16.1 (d, J = 2.0 Hz), 16.0 (d, J = 2.1 Hz). 31 P NMR (162 MHz, CDCl3) δ 25.99.HRMS: [M+Na] + m / z calcd for C 12 H 19 NaO3PS + : 297.0685, found: 297.0686.

[0053] Compound 5: O,O,O',O'-Tetraethyl S,S'-(2-oxo-1-phenylindoline-3,3-diyl)bis(phosphorothioate) (O,O,O',O'-Tetraethyl S,S'-(2-oxo-1-phenylindoline-3,3-diyl)bis(phosphorothioate)), yield: 24.4 mg, 40%, yellow liquid; structural formula: .

[0054] NMR data of compound 5: 1 H NMR (400 MHz, CDCl3) δ 7.32 – 7.27 (m, 2H),6.87 – 6.81 (m, 2H), 4.51 – 4.43 (m, 1H), 4.16 – 3.89 (m, 4H), 3.79 (s, 3H),1.73 (d, J = 7.1 Hz, 3H), 1.29 – 1.22 (m, 6H). 13 C NMR (101 MHz, CDCl3) δ 159.1, 135.7 (d, J = 5.6 Hz), 128.3, 114.1, 63.6 (d, J = 1.3 Hz), 63.5 (d, J= 1.3 Hz), 55.5, 45.7 (d, J = 3.7 Hz), 24.9 (d, J = 7.2 Hz), 16.1 (d, J = 7.4Hz). 31P NMR (162 MHz, CDCl3) δ 26.17. HRMS: [M+Na] + m / z calcd for C 13 H 21 NaO4PS + :327.0790, found: 327.0784.

[0055] Compound 6: O,O,O',O'-Tetraethyl S,S'-(2-oxo-1-phenylindoline-3,3-diyl)bis(phosphorothioate) (O,O,O',O'-Tetraethyl S,S'-(2-oxo-1-phenylindoline-3,3-diyl)bis(phosphorothioate)), yield: 41.5 mg, 71%, yellow liquid; structural formula: .

[0056] NMR data of compound 6: 1 H NMR (400 MHz, CDCl3) δ 7.39 – 7.33 (m, 2H), 7.05 – 6.97 (m, 2H), 4.54 – 4.46 (m, 1H), 4.17 – 4.06 (m, 1H), 4.04 – 3.89(m, 3H), 1.73 (dd, J = 7.2, 1.2 Hz, 3H), 1.29 – 1.21 (m, 6H). 13 C NMR (101MHz, CDCl3) δ 162.2 (d, J = 246.2 Hz), 139.6 (dd, J = 4.9, 3.3 Hz), 128.9 (d,J = 8.2 Hz), 115.6 (d, J = 21.5 Hz), 63.7 (d, J = 2.3 Hz), 63.6 (d, J = 2.6Hz), 45.2 (d, J = 3.6 Hz), 24.9 (d, J = 7.9 Hz), 16.13 (d, J = 1.9 Hz), 16.05(d, J = 2.0 Hz). 31 P NMR (162 MHz, CDCl3) δ 25.66. 19 F NMR (376 MHz, CDCl3) δ -114.66. HRMS: [M+Na] + m / z calcd for C 12H 18 FNaO3PS + : 315.0591, found: 315.0593.

[0057] Compound 7: O,O,O',O'-Tetraethyl S,S'-(2-oxo-1-phenylindoline-3,3-diyl)bis(phosphorothioate) (O,O,O',O'-Tetraethyl S,S'-(2-oxo-1-phenylindoline-3,3-diyl)bis(phosphorothioate)), yield: 49.0 mg, 74%, yellow liquid; structural formula: .

[0058] NMR data of compound 7: 1 H NMR (400 MHz, CDCl3) δ 7.36 – 7.26 (m, 4H), 4.51 – 4.43 (m, 1H), 4.17 – 4.08 (m, 1H), 4.05 – 3.88 (m, 3H), 1.72 (dd, J =7.3, 1.3 Hz, 3H), 1.28 – 1.22 (m, 6H). 13 C NMR (101 MHz, CDCl3) δ 143.0 (d, J = 5.5 Hz), 133.4, 128.9, 127.5, 63.6 (d, J = 5.9 Hz), 45.6 (d, J = 3.5 Hz), 24.7 (d, J = 7.1 Hz), 16.1 (d, J = 7.6 Hz). 31 P NMR (162 MHz, CDCl3) δ 25.51.HRMS: [M+Na] + m / z calcd for C 12 H 18 NaClO3PS + : 331.0295, found: 331.0292.

[0059] Compound 8: O,O,O',O'-Tetraethyl S,S'-(2-oxo-1-phenylindoline-3,3-diyl)bis(phosphorothioate) (O,O,O',O'-Tetraethyl S,S'-(2-oxo-1-phenylindoline-3,3-diyl)bis(phosphorothioate)), yield: 53.5 mg, 76%, yellow liquid; structural formula: .

[0060] NMR data of compound 8: 1 H NMR (400 MHz, CDCl3) δ 7.48 – 7.42 (m, 2H),7.29 – 7.24 (m, 2H), 4.50 – 4.42 (m, 1H), 4.16 – 4.07 (m, 1H), 4.04 – 3.90(m, 3H), 1.72 (dd, J = 7.2, 1.3 Hz, 3H), 1.28 – 1.23 (m, 6H). 13 C NMR (101MHz, CDCl3) δ 142.9 (d, J = 4.8 Hz), 131.9, 128.96, 121.5, 63.8 (d, J = 1.6Hz), 63.7 (d, J = 1.6 Hz), 45.3 (d, J = 3.5 Hz), 24.6 (d, J = 7.9 Hz), 16.1 (d, J = 1.4 Hz), 16.06 (d, J = 1.3 Hz). 31 P NMR (162 MHz, CDCl3) δ 25.47.HRMS: [M+H] + m / z calcd for C 12 H 19 BrO3PS + : 352.9970, found: 352.9966.

[0061] Compound 9: O,O,O',O'-Tetraethyl S,S'-(2-oxo-1-phenylindoline-3,3-diyl)bis(phosphorothioate) (O,O,O',O'-Tetraethyl S,S'-(2-oxo-1-phenylindoline-3,3-diyl)bis(phosphorothioate)), yield: 53.8 mg, 81%, yellow liquid; structural formula: .

[0062] NMR data of compound 9: 1H NMR (400 MHz, CDCl3) δ 8.01 – 7.95 (m, 2H), 7.47 – 7.41 (m, 2H), 4.54 – 4.45 (m, 1H), 4.13 – 4.03 (m, 1H), 4.01 – 3.84(m, 6H), 1.73 (d, J = 7.2 Hz, 3H), 1.24 – 1.18 (m, 6H). 13 C NMR (101 MHz, CDCl3) δ 166.9, 148.9 (d, J = 4.5 Hz), 130.1, 129.5, 127.3, 63.7 (d, J = 1.8Hz), 63.7 (d, J = 2.1 Hz), 52.3, 45.4 (d, J = 3.5 Hz), 24.5 (d, J = 8.2 Hz),16.1 (d, J = 7.5 Hz). 31 P NMR (162 MHz, CDCl3) δ 25.34. HRMS: [M+Na] + m / z calcdfor C 14 H 21 NaO5PS + : 355.0740, found: 355.0743.

[0063] Compound 10: (O,O,O',O'-Tetraethyl S,S'-(2-oxo-1-phenylindoline-3,3-diyl)bis(phosphorothioate), yield: 49.2 mg, 74%, yellow liquid; structural formula: .

[0064] NMR data of compound 10: 1 H NMR (400 MHz, CDCl3) δ 7.41 – 7.36 (m, 2H), 7.05 – 7.00 (m, 2H), 4.53 – 4.44 (m, 1H), 4.14 – 4.04 (m, 1H), 4.02 – 3.83(m, 3H), 2.28 (s, 3H), 1.73 (dd, J = 7.2, 1.2 Hz, 3H), 1.28 – 1.21 (m, 6H).13 C NMR (101 MHz, CDCl3) δ 169.6, 150.1, 141.3 (d, J = 5.0 Hz), 128.3, 121.9,63.7 (d, J = 5.9 Hz), 45.4 (d, J = 3.6 Hz), 24.8 (d, J = 7.8 Hz), 21.3, 16.1(d, J = 7.4 Hz). 31 P NMR (162 MHz, CDCl3) δ 25.71. HRMS: [M+Na] + m / z calcd forC 14 H 21 NaO5PS + : 355.0740, found: 355.0745.

[0065] Compound 11: O,O,O',O'-Tetraethyl S,S'-(2-oxo-1-phenylindoline-3,3-diyl)bis(phosphorothioate) (O,O,O',O'-Tetraethyl S,S'-(2-oxo-1-phenylindoline-3,3-diyl)bis(phosphorothioate)), yield: 46.2 mg, 73%, yellow liquid; structural formula: .

[0066] NMR data of compound 11: 1 H NMR (400 MHz, CDCl3) δ 7.38 – 7.30 (m, 4H),7.28 – 7.22 (m, 1H), 4.33 (dt, J = 10.9, 8.2 Hz, 1H), 4.09 – 4.02 (m, 1H),3.98 – 3.88 (m, 2H), 3.81 – 3.74 (m, 1H), 1.90 – 1.86 (m, 2H), 1.58 – 1.48(m, 1H), 1.24 – 1.17 (m, 6H), 0.92 (t, J = 7.0 Hz, 6H). 13 C NMR (101 MHz, CDCl3) δ 142.9 (d, J = 2.7 Hz), 128.7, 127.7, 127.6, 63.4 (d, J = 5.2 Hz), 49.2 (d, J = 3.6 Hz), 47.2 (d, J = 8.7 Hz), 26.1, 22.9, 21.9, 16.1 (d,J = 4.8Hz), 15.98 (d,J = 4.7Hz). 31 P NMR (162 MHz, CDCl3) δ 26.21. HRMS: [M+Na] + m / z calcd for C 15 H 25 NaO3PS + : 339.1154, found: 339.1158.

[0067] Compound 12: O,O,O',O'-Tetraethyl S,S'-(2-oxo-1-phenylindoline-3,3-diyl)bis(phosphorothioate) (O,O,O',O'-Tetraethyl S,S'-(2-oxo-1-phenylindoline-3,3-diyl)bis(phosphorothioate)), yield: 45.4 mg, 75%, yellow liquid; structural formula: .

[0068] NMR data of compound 12: 1 H NMR (400 MHz, CDCl3) δ 7.37 – 7.28 (m, 4H),7.27 – 7.21 (m, 1H), 4.28 – 4.22 (m, 1H), 4.11 – 3.99 (m, 1H), 3.98 – 3.85(m, 2H), 3.84 – 3.75 (m, 1H), 2.06 – 1.90 (m, 2H), 1.43 – 1.33 (m, 1H), 1.30 – 1.24 (m, 1H), 1.23 – 1.15 (m, 6H), 0.90 (t, J = 7.3 Hz, 3H). 13 C NMR (101MHz, CDCl3) δ 142.8 (d, J = 3.0 Hz), 128.6, 127.7, 127.6, 63.4 (d, J = 2.6Hz), 63.4 (d, J = 2.9 Hz), 50.8 (d, J = 3.6 Hz), 40.4 (d, J = 8.7 Hz), 21.0,16.1 (d, J = 4.3 Hz), 16.0 (d, J = 4.1 Hz), 13.7. 31 P NMR (162 MHz, CDCl3) δ30.70. HRMS: [M+Na] + m / z calcd for C 14 H 23 NaO3PS + : 325.0998, found: 325.0999.

[0069] Compound 13: O,O,O',O'-Tetraethyl S,S'-(2-oxo-1-phenylindoline-3,3-diyl)bis(phosphorothioate) (O,O,O',O'-Tetraethyl S,S'-(2-oxo-1-phenylindoline-3,3-diyl)bis(phosphorothioate)), yield: 46.7 mg, 81%, yellow liquid; structural formula: .

[0070] NMR data of compound 13: 1 H NMR (400 MHz, CDCl3) δ 7.36 – 7.28 (m, 4H),7.28 – 7.23 (m, 1H), 4.18 – 4.11 (m, 1H), 4.08 – 4.02 (m, 1H), 3.99 – 3.86(m, 2H), 3.85 – 3.75 (m, 1H), 2.16 – 1.92 (m, 2H), 1.22 – 1.17 (m, 6H), 0.92(t, J = 7.3 Hz, 3H). 13 C NMR (101 MHz, CDCl3) δ 142.6 (d, J = 3.3 Hz), 128.6,127.8, 127.6, 63.5 (d, J = 3.4 Hz), 63.4 (d, J = 3.6 Hz), 52.8 (d, J = 3.6Hz), 31.6 (d, J = 8.7 Hz), 16.1 (d, J = 7.4 Hz), 16.0 (d, J = 7.4 Hz), 12.5. 31 P NMR (162 MHz, CDCl3) δ 26.27. HRMS: [M+H] + m / z calcd for C 13 H 22 O3PS + :289.1022, found: 289.1030.

[0071] Compound 14: O,O,O',O'-Tetraethyl S,S'-(2-oxo-1-phenylindoline-3,3-diyl)bis(phosphorothioate) (O,O,O',O'-Tetraethyl S,S'-(2-oxo-1-phenylindoline-3,3-diyl)bis(phosphorothioate)), yield: 50.6 mg, 80%, yellow liquid; structural formula: .

[0072] NMR data of compound 14: 1 H NMR (400 MHz, CDCl3) δ 7.30 – 7.21 (m, 4H),7.21 – 7.14 (m, 1H), 4.19 – 4.12 (m, 1H), 4.03 – 3.94 (m, 1H), 3.92 – 3.66(m, 3H), 2.04 – 1.81 (m, 2H), 1.32 – 1.16 (m, 4H), 1.17 – 1.05 (m, 6H), 0.78 (t, J = 7.0 Hz, 3H). 13 C NMR (101 MHz, CDCl3) δ 142.9 (d, J = 3.2 Hz), 128.7,127.7, 127.6, 63.44 (d, J = 2.5 Hz), 63.39 (d, J = 2.8 Hz), 51.1 (d, J = 3.5Hz), 38.1 (d, J = 8.7 Hz), 29.9, 22.4, 16.1 (d, J = 3.8 Hz), 16.0 (d, J = 3.8Hz), 14.0. 31 P NMR (162 MHz, CDCl3) δ 26.28. HRMS: [M+Na] + m / z calcd forC 15 H 25 NaO3PS + : 339.1154, found: 339.1159.

[0073] Compound 15: O,O,O',O'-Tetraethyl S,S'-(2-oxo-1-phenylindoline-3,3-diyl)bis(phosphorothioate) (O,O,O',O'-Tetraethyl S,S'-(2-oxo-1-phenylindoline-3,3-diyl)bis(phosphorothioate)), yield: 61.9 mg, 81%, yellow liquid; structural formula: .

[0074] NMR data of compound 15: 1 H NMR (400 MHz, CDCl3) δ 7.38 – 7.32 (m, 4H),7.30 – 7.25 (m, 1H), 4.31 – 4.25 (m, 1H), 4.15 – 4.04 (m, 1H), 4.01 – 3.80(m, 3H), 3.39 (t, J = 6.6 Hz, 2H), 2.27 – 2.08 (m, 2H), 2.03 – 1.90 (m, 1H), 1.87 – 1.77 (m, 1H), 1.25 – 1.20 (m, 6H). 13 C NMR (101 MHz, CDCl3) δ 142.1 (d,J = 3.5 Hz), 128.9, 127.9, 127.6, 63.7 (d, J = 4.0 Hz), 63.6 (d, J = 4.2 Hz), 50.2 (d, J = 3.5 Hz), 36.8 (d, J = 8.4 Hz), 33.0, 30.8, 16.1 (d, J = 7.6 Hz). 31 P NMR (162 MHz, CDCl3) δ 25.70. HRMS: [M+Na] + m / z calcd for C 14 H 22 BrNaO3PS + :403.0103, found: 403.0087.

[0075] Compound 16: O,O,O',O'-Tetraethyl S,S'-(2-oxo-1-phenylindoline-3,3-diyl)bis(phosphorothioate) (O,O,O',O'-Tetraethyl S,S'-(2-oxo-1-phenylindoline-3,3-diyl)bis(phosphorothioate)), yield: 64.2 mg, 66%, yellow liquid; structural formula: .

[0076] NMR data of compound 16: 1 H NMR (400 MHz, CDCl3) δ 7.78 – 7.70 (m, 2H),7.35 – 7.23 (m, 7H), 4.24 – 4.16 (m, 1H), 4.10 – 4.02 (m, 1H), 3.96 (t, J =6.4 Hz, 2H), 3.92 – 3.77 (m, 3H), 2.45 (s, 3H), 2.06 – 1.86 (m, 2H), 1.67 –1.60 (m, 2H), 1.45 – 1.33 (m, 1H), 1.29 – 1.24 (m, 1H), 1.20 – 1.16 (m, 6H). 13 C NMR (101 MHz, CDCl3) δ 144.9, 142.3 (d, J = 3.6 Hz), 133.2, 130.0, 128.8,128.0, 127.8, 127.6, 70.2, 63.6 (d, J = 4.1 Hz), 63.5 (d, J = 4.5 Hz), 50.7(d, J = 3.6 Hz), 37.6 (d, J = 8.4 Hz), 28.5, 23.8, 21.8, 16.0 (d, J = 7.6Hz). 31 P NMR (162 MHz, CDCl3) δ 25.82. HRMS: [M+H] + m / z calcd for C 22 H 32 O6PS2 + :487.1372, found: 487.1369.

[0077] Compound 17: O,O,O',O'-Tetraethyl S,S'-(2-oxo-1-phenylindoline-3,3-diyl)bis(phosphorothioate) (O,O,O',O'-Tetraethyl S,S'-(2-oxo-1-phenylindoline-3,3-diyl)bis(phosphorothioate)), yield: 47.6 mg, 66%, yellow liquid; structural formula: .

[0078] NMR data of compound 17: 1 H NMR (400 MHz, CDCl3) δ 7.36 – 7.29 (m, 4H),7.29 – 7.21 (m, 1H), 4.30 – 4.21 (m, 1H), 4.12 – 4.02 (m, 1H), 3.98 – 3.76(m, 3H), 3.64 (s, 3H), 2.31 (t, J = 7.4 Hz, 2H), 2.12 – 1.95 (m, 2H), 1.78 –1.65 (m, 1H), 1.64 – 1.51 (m, 1H), 1.27 – 1.15 (m, 6H). 13 C NMR (101 MHz, CDCl3) δ 173.7, 142.3 (d, J = 3.4 Hz), 128.8, 127.8, 127.6, 63.6 (d, J = 2.9Hz), 63.5 (d, J = 3.2 Hz), 51.7, 50.7 (d, J = 3.5 Hz), 37.6 (d, J = 8.5 Hz), 33.5, 23.1, 16.04 (d, J = 2.2 Hz), 15.97 (d, J = 2.1 Hz). 31 P NMR (162 MHz, CDCl3) δ 25.86. HRMS: [M+H] + m / z calcd for C 16 H 26 O5PS + : 361.1233, found:361.1232.

[0079] Compound 18: S-Benzhydryl O,O-diethylphosphorothioate, yield: 35.0 mg, 52%, yellow liquid; structural formula: .

[0080] NMR data of compound 18: 1 H NMR (400 MHz, CDCl3) δ 7.39 – 7.32 (m, 4H), 7.27 – 7.22 (m, 4H), 7.20 – 7.14 (m, 2H), 5.55 (d, J = 11.6 Hz, 1H), 4.00 –3.88 (m, 2H), 3.84 – 3.70 (m, 2H), 1.13 – 1.05 (m, 6H). 13 C NMR (101 MHz, CDCl3) δ 141.6 (d, J = 5.6 Hz), 128.8, 128.4, 127.7, 63.7 (d, J = 5.6 Hz), 54.4 (d, J = 3.2 Hz), 16.0 (d, J = 7.6 Hz). 31 P NMR (162 MHz, CDCl3) δ 25.33.HRMS: [M+Na] + m / z calcd for C 17 H 21 NaO3PS +: 359.0841, found: 359.0842.

[0081] Compound 19: O,O,O',O'-Tetraethyl S,S'-(2-oxo-1-phenylindoline-3,3-diyl)bis(phosphorothioate) (O,O,O',O'-Tetraethyl S,S'-(2-oxo-1-phenylindoline-3,3-diyl)bis(phosphorothioate)), yield: 37.2 mg, 50%, yellow liquid; structural formula: .

[0082] NMR data of compound 19: 1 H NMR (400 MHz, CDCl3) δ 7.41 – 7.32 (m, 4H), 7.05 – 6.96 (m, 4H), 5.63 (d, J = 11.2 Hz, 1H), 4.08 – 3.98 (m, 2H), 3.93 –3.84 (m, 2H), 1.18 (dt, J = 7.1, 0.9 Hz, 6H). 13 C NMR (101 MHz, CDCl3) δ 163.2(d, J = 247.2 Hz), 137.3 (dd, J = 5.6, 3.3 Hz), 130.0 (d, J = 8.1 Hz), 115.8(d, J =21.6 Hz), 63.8 (d, J = 6.0 Hz), 52.9 (d, J = 3.2 Hz), 16.05 (d, J =7.5 Hz). 31 P NMR (162 MHz, CDCl3) δ 24.69. 19 F NMR (376 MHz, CDCl3) δ -114.45.HRMS: [M+Na] + m / z calcd for C 17 H 19 F2NaO3PS + :395.0653, found: 395.0652.

[0083] Compound 20: O,O,O',O'-Tetraethyl S,S'-(2-oxo-1-phenylindoline-3,3-diyl)bis(phosphorothioate) (O,O,O',O'-Tetraethyl S,S'-(2-oxo-1-phenylindoline-3,3-diyl)bis(phosphorothioate)), yield: 31.5 mg, 55%, yellow liquid; structural formula: .

[0084] NMR data of compound 20: 1 H NMR (400 MHz, CDCl3) δ 7.50 – 7.40 (m, 1H),7.28 – 7.19 (m, 3H), 4.86 – 4.81 (m, 1H), 4.29 – 4.12 (m, 4H), 3.13 – 3.06(m, 1H), 2.93 – 2.86 (m, 1H), 2.73 – 2.63 (m, 1H), 2.35 – 2.27 (m, 1H), 1.41– 1.36 (m, 6H). 13 C NMR (101 MHz, CDCl3) δ 143.6, 142.6 (d, J =8.8 Hz), 128.3,127.0, 125.2, 124.9, 63.9 (d, J = 5.6 Hz), 63.8 (d, J = 5.8 Hz), 50.1 (d, J =3.4 Hz), 36.3 (d, J = 3.3 Hz), 31.1, 16.3 (d, J = 7.4 Hz). 31 P NMR (162 MHz, CDCl3) δ 26.84. HRMS: [M+Na] + m / z calcd for C 13 H 19 NaO3PS + : 309. 0685, found: 309.0686.

[0085] Compound 21: O,O-Diethyl S-(9H-fluoren-9-yl) phosphorothioate, yield: 43.5 mg, 65%, yellow liquid; structural formula: .

[0086] NMR data of compound 21:1 H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 7.8 Hz,2H), 7.71 (d, J = 7.4 Hz, 2H), 7.45 – 7.31 (m, 4H), 5.47 (d, J = 15.5 Hz,1H), 4.39 – 4.13 (m, 4H), 1.40 (t, J = 7.1 Hz, 6H). 13 C NMR (101 MHz, CDCl3) δ144.4 (d, J = 5.0 Hz), 140.5, 128.8, 127.9, 126.1, 120.2, 64.3 (d, J = 6.6Hz), 48.5 (d, J = 3.8 Hz), 16.3 (d, J = 7.3 Hz). 31 P NMR (162 MHz, CDCl3) δ26.60. HRMS: [M+H] + m / z calcd for C 17 H 20 O3PS + : 335.0865, found: 335.0862.

[0087] Compound 22: O,O,O',O'-Tetraethyl S,S'-(2-oxo-1-phenylindoline-3,3-diyl)bis(phosphorothioate) (O,O,O',O'-Tetraethyl S,S'-(2-oxo-1-phenylindoline-3,3-diyl)bis(phosphorothioate)), yield: 28.5 mg, 45%, yellow liquid; structural formula: .

[0088] NMR data of compound 22: 1 H NMR (400 MHz, CDCl3) δ 7.34 (d, J = 8.4 Hz,2H), 7.29 (d, J = 8.2 Hz, 2H), 4.17 – 4.06 (m, 2H), 4.05 – 3.97 (m, 4H), 1.30(s, 9H), 1.27 (t, J = 7.2 Hz, 6H). 13 C NMR (101 MHz, CDCl3) δ 150.9, 134.6 (d,J = 5.6 Hz), 128.8, 125.8, 63.6 (d, J = 5.9 Hz), 34.8 (d, J = 3.9 Hz), 34.7,31.5, 16.1 (d, J = 7.5 Hz). 31 P NMR (162 MHz, CDCl3) δ 26.84. HRMS: [M+Na] + m / zcalcd for C 15 H 25 NaO3PS + : 339.1154, found: 339.1157.

[0089] Compound 23: O,O,O',O'-Tetraethyl S,S'-(2-oxo-1-phenylindoline-3,3-diyl)bis(phosphorothioate) (O,O,O',O'-Tetraethyl S,S'-(2-oxo-1-phenylindoline-3,3-diyl)bis(phosphorothioate)), yield: 34.3 mg, 51%, yellow liquid; structural formula: .

[0090] NMR data of compound 23: 1 H NMR (400 MHz, CDCl3) δ 7.60 – 7.53 (m, 4H), 7.47 – 7.40 (m, 4H), 7.38 – 7.30 (m, 1H), 4.21 – 3.99 (m, 6H), 1.29 (dt, J =7.1, 0.9 Hz, 6H). 13 C NMR (101 MHz, CDCl3) δ 140.8, 140.7, 136.7 (d, J = 5.3Hz), 129.5, 129.0, 127.6, 127.5, 127.2, 63.7 (d, J = 5.9 Hz), 34.9 (d, J =3.9 Hz), 16.1 (d, J = 7.4 Hz). 31 P NMR (162 MHz, CDCl3) δ 26.71. HRMS: [M+Na] + m / z calcd for C 17 H 21 NaO3PS +: 359.0841, found: 359.0845.

[0091] Compound 24: O,O,O',O'-Tetraethyl S,S'-(2-oxo-1-phenylindoline-3,3-diyl)bis(phosphorothioate) (O,O,O',O'-Tetraethyl S,S'-(2-oxo-1-phenylindoline-3,3-diyl)bis(phosphorothioate)), yield: 33.1 mg, 57%, yellow liquid; structural formula: .

[0092] NMR data of compound 24: 1 H NMR (400 MHz, CDCl3) δ 7.32 – 7.25 (m, 2H), 6.91 – 6.80 (m, 2H), 4.22 – 3.96 (m, 6H), 3.80 (s, 3H), 1.32 – 1.68 (m, 6H). 13 C NMR (101 MHz, CDCl3) δ 159.1, 130.1, 129.5 (d, J = 5.7 Hz), 114.0, 63.5 (d, J = 5.7 Hz), 55.3, 34.6 (d, J = 3.8 Hz), 16.0 (d, J = 7.5 Hz). 31 P NMR (162 MHz, CDCl3) δ 26.94. HRMS: [M+Na] + m / z calcd for C 12 H 19 NaO4PS + : 313.0634, found: 313.0633.

[0093] Compound 25: O,O,O',O'-Tetraethyl S,S'-(2-oxo-1-phenylindoline-3,3-diyl)bis(phosphorothioate) (O,O,O',O'-Tetraethyl S,S'-(2-oxo-1-phenylindoline-3,3-diyl)bis(phosphorothioate)), yield: 35.3 mg, 54%, yellow liquid; structural formula: .

[0094] NMR data of compound 25: 1H NMR (400 MHz, CDCl3) δ 7.93 (d, J = 2.5 Hz,1 H), 7.73 (d, J = 1.7 Hz, 1H), 7.69 – 7.63 (m, 2H), 7.51 – 7.42 (m, 2H), 6.48 – 6.47 (m, 1H), 4.20 – 3.99 (m, 6H), 1.30 (t, J = 7.1, 6H). 13 C NMR (101MHz, CDCl3) δ 141.4, 139.7, 136.0 (d, J = 5.0 Hz), 130.2, 126.9, 119.4,107.96, 63.8 (d, J = 5.9 Hz), 34.6 (d, J = 3.8 Hz), 16.2 (d, J = 7.3 Hz). 31 PNMR (162 MHz, CDCl3) δ 26.50. HRMS: [M+Na] + m / z calcd for C 14 H 19 N2NaO3PS + :349.0746, found: 349.0755.

[0095] The above are merely preferred embodiments of the present invention, but the scope of protection of the present invention is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the scope of the technology disclosed in the present invention should be included within the scope of protection of the present invention.

Claims

1. A process for the preparation of alkyl thiophosphates by direct functionalization of C-H bonds, characterized in that, The method comprises the following steps: adding compound 1, P(O)SH compound 2a, a photocatalyst, a copper catalyst and an oxidant into a solvent, carrying out a reaction under a protective atmosphere and visible light irradiation, and obtaining the alkyl thiophosphate through post-treatment after the reaction is completed; wherein, the structural formula of the compound 1 is ; the structural formula of the P(O)SH compound 2a is ; the structural formula of the alkyl thiophosphate is ; wherein, R is selected from H, aryl or alkyl.

2. The process for the preparation of alkyl thiophosphates by direct functionalization of C-H bonds according to claim 1, characterized in that, The molar ratio of the compound 1, P(O)SH compound 2a, the photocatalyst, the copper catalyst and the oxidant is 1: (2-4): (0.01-0.05): (0.1-0.2): (2-3).

3. The method of preparing alkyl thiophosphates by direct functionalization of C-H bonds according to claim 1, characterized in that, The photocatalyst is selected from 2,4,5,6-tetra (9H-carbazole-9-yl) phthalonitrile and / or eosin Y.

4. The method of preparing alkyl thiophosphates by direct functionalization of C-H bonds according to claim 1, characterized in that, The copper catalyst is selected from at least one of CuSO4, Cu(OAc)2, Cu2O, CuBr2, CuO, CuCl and CuBr.

5. The method of preparing alkyl thiophosphates by direct functionalization of C-H bonds according to claim 1, characterized in that, The oxidant is selected from at least one of K2S2O8, tert-butyl hydroperoxide and tert-butyl peroxobenzoate.

6. The method of preparing alkyl thiophosphates by direct functionalization of C-H bonds according to claim 1, characterized in that, The solvent is a mixed solution of water and an organic solvent; the organic solvent is selected from acetonitrile.

7. The method of preparing alkyl thiophosphates by direct functionalization of C-H bonds according to claim 6, characterized in that, The amount ratio of the water, the organic solvent and the compound 1 is 0.2-0.5 mmol: 1-3 mL: 0.2 mmol.

8. The method of preparing alkyl thiophosphates by direct functionalization of C-H bonds according to claim 1, characterized in that, The visible light is blue light; the power of the blue light is 6-32 W.

9. The method of preparing alkyl thiophosphates by direct functionalization of C-H bonds according to claim 1, characterized in that, The temperature of the reaction is room temperature, and the time of the reaction is 4-24 hours.

10. The method of preparing alkyl thiophosphates by direct functionalization of C-H bonds according to claim 1, characterized in that, The alkyl thiophosphates have the formula: , , , , , , , , , , , , , , , , , , , , , or .

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