A method for preparing aryl selenothiophosphonate compounds

Abstract

The application discloses a preparation method of aryl selenothiophosphate compounds and belongs to the field of organic synthesis chemistry. The method uses isonitrile, diaryl diselenide and O, O-dialkyl thiophosphate as substrates, uses iodide as a catalyst, and reacts in a solvent at 0-80 DEG C. After post-treatment, aryl selenothiophosphate compounds are obtained. The method uses common and cheap iodide as a catalyst, does not use any metal and organic catalyst, does not need any additive, has mild reaction conditions, high product yield, simple operation, and is green and environment-friendly. The reagent and catalyst used are rich in industrial sources and easy to obtain, the production cost is low, the product has high purity, and the method has good industrial application prospect.

Description

Technical Field

[0001] This invention belongs to the field of organic synthetic chemistry, and specifically relates to a method for preparing aryl selenide thiophosphate compounds. Background Technology

[0002] Phosphophosphates are an important class of sulfur- and phosphorus-containing organic molecules, whose structural units are widely found in bioactive natural products, drug molecules (such as antiviral drugs), and agrochemicals. Due to their unique PS bonds, these compounds typically exhibit good lipophilicity and metabolic stability, making them a focus of attention in drug design and agrochemical development. Meanwhile, selenium, an essential trace element for the human body, exists primarily as selenocysteine ​​in the active sites of approximately 25 selenoproteins, participating in key physiological processes such as antioxidant defense, thyroid hormone metabolism, and immune regulation. To date, organoselenium compounds have demonstrated indispensable application value in numerous fields, encompassing agricultural production, antioxidant and other bioactive research, organic synthesis, and optoelectronic materials.

[0003] There are many traditional methods for constructing C(sp³)-SP bonds, such as the reductive coupling reaction of sulfonyl chloride and phosphite catalyzed by divalent copper chloride and proline, the oxidative coupling reaction of thiols and phosphites catalyzed by nickel acetate and Lewis acids, the oxidative cross-dehydrogenation coupling reaction of thiols and phosphites catalyzed by iron phthalocyanine, and the three-component reaction of arylboronic acids, sulfur, and P(O)-H compounds catalyzed by copper trifluoromethanesulfonate and bipyridine. However, all of these methods have significant drawbacks: the reaction systems are complex, they rely on expensive transition metal catalysts, and require large amounts of alkali, causing severe corrosion to equipment, resulting in high costs and failing to meet the actual needs of industrial production and market supply.

[0004] Therefore, developing a method for preparing aryl selenide thiophosphate compounds that does not use precious metal catalysts, has mild reaction conditions, is easy to operate, has low cost, and produces high product yields has significant industrial application value and practical significance. Summary of the Invention

[0005] The technical problem to be solved by the present invention is to overcome the defects of the existing methods for preparing aryl selenide thiophosphate compounds, such as dependence on transition metal catalysts, harsh reaction conditions, and high cost.

[0006] To solve the above-mentioned technical problems, the solution of the present invention is: In a first aspect, the present invention provides a method for preparing arylselenized thiophosphate compounds, comprising the following steps: Isocyanates, diaryl diselenide, O,O-dialkyl thiophosphate and iodide catalyst were added to the solvent in sequence and reacted at 0~80℃. After the reaction was complete, the resulting reaction solution was extracted, dried, concentrated, and separated by column chromatography to obtain aryl selenide thiophosphate compounds.

[0007] Preferably, the iodide catalyst is at least one selected from iodosuccinimide, iodine, ammonium iodide, sodium iodide, potassium iodide, tetramethylammonium iodide, and tetrabutylammonium iodide.

[0008] This invention uses common, inexpensive, and readily available iodides as the catalyst for the reaction. It does not use any metal or organic catalysts, does not require any additives, has mild reaction conditions, high product yield, simple operation, and is green and environmentally friendly.

[0009] Preferably, the isonitrile is at least one selected from isocyanobenzene, 1-isocyano-4-methylbenzene, 1-isocyano-3-methylbenzene, 1-isocyano-2-methylbenzene, 1-isocyano-4-methoxybenzene, 1-isocyano-3-methoxybenzene, 1-isocyano-2-methoxybenzene, 1-isocyano-4-trifluoromethylbenzene, 1-isocyano-4-fluorobenzene, 1-isocyano-4-chlorobenzene, 1-isocyano-4-bromobenzene, 1-isocyano-4-iodobenzene, 1-isocyano-4-tert-butylbenzene, 1-isocyano-4-ethylbenzene, 1-isocyano-4-isopropylbenzene, 1-isocyano-4-nitrobenzene, isocyanoethane, isocyanopropane, and tert-butylisocyanate.

[0010] Preferably, the diaryl diselenide is at least one selected from diphenyl diselenide, di(4-methylphenyl)diselenide, di(3-methylphenyl)diselenide, di(2-methylphenyl)diselenide, di(4-methoxyphenyl)diselenide, di(4-ethylphenyl)diselenide, di(4-tert-butylphenyl)diselenide, di(4-isopropylphenyl)diselenide, di(4-fluorophenyl)diselenide, di(4-chlorophenyl)diselenide, di(4-bromophenyl)diselenide, di(4-iodophenyl)diselenide, di(2-furanyl)diselenide, and di(2-thiophenyl)diselenide.

[0011] Preferably, the O,O-dialkyl thiophosphate is at least one selected from O,O-dimethyl thiophosphate, O,O-diethyl thiophosphate, O,O-dipropyl thiophosphate, O,O-diisopropyl thiophosphate, O,O-di-tert-butyl thiophosphate, O,O-di-sec-butyl thiophosphate, O,O-di-tert-butyl thiophosphate, and O,O-dibenzyl thiophosphate.

[0012] Preferably, the solvent is at least one selected from N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile, toluene, tetrahydrofuran, 1,4-dioxane, 1,2-dichloroethane, dimethyl sulfoxide, methanol, ethanol, dichloromethane, chloroform, and ethyl acetate.

[0013] Preferably, the molar ratio of the iodide catalyst to the isonitrile is 0.1~1.0:1; the molar ratio of the diaryldiselenes to the isonitriles is 0.1~1.2:1; the molar ratio of the O,O-dialkylthiophosphate to the isonitriles is 0.1~1.0:1; and the molar ratio of the isonitriles to the solvent is 1:50~200.

[0014] Preferably, the reaction temperature is 20-80℃ and the reaction time is 12-24h.

[0015] Preferably, the aryl selenide thiophosphate compound is selected from at least one of the following formulas: 3-4ba, 3-4ca, 3-4da, 3-4ea, 3-4fa, 3-4ga, 3-4ha, 3-4ia, 3-4ja, and 3-4ka.

[0016]

[0017] Compared with the prior art, the present invention has the following beneficial effects: The catalyst is inexpensive and readily available, and is environmentally friendly: This invention uses common and inexpensive iodides (especially iodosuccinimide) as catalysts, without using any transition metals or organic catalysts, without adding any additional bases or additives, the reaction conditions are mild, environmentally friendly, and the operation is simple.

[0018] Mild reaction conditions and high product yield: This invention can be carried out efficiently under mild conditions of 0~80℃, with short reaction time and high product yield (the yield in the examples can reach 48%~90%). The product is easy to separate and purify, and the product purity is high.

[0019] The raw materials are widely available and inexpensive: the reagents and catalysts used in this invention are abundant and readily available in the industry, have low production costs, and have good industrial application prospects and promotion value.

[0020] This invention expands the methodology of organic synthesis: It provides a new method for constructing C(sp³)-SP bonds through iodide-catalyzed multicomponent reactions, offering a new synthetic strategy for the intersection of organophosphorus chemistry and organoselenium chemistry. Attached Figure Description

[0021] Figure 1 The ¹H NMR spectrum of compound 3-4ba in the embodiments of the present invention is shown.

[0022] Figure 2 The image shows the ¹³C NMR spectrum of compound 3-4ba in an embodiment of the present invention.

[0023] Figure 3 The image shows the ³¹P NMR spectrum of compound 3-4ba in an embodiment of the present invention.

[0024] Figure 4 The ¹H NMR spectrum of compound 3-4ca in the embodiments of the present invention is shown.

[0025] Figure 5 The image shows the ¹³C NMR spectrum of compound 3-4ca in an embodiment of the present invention.

[0026] Figure 6 The image shows the ³¹P NMR spectrum of compound 3-4ca in the embodiments of the present invention.

[0027] Figure 7 The ¹H NMR spectrum of compound 3-4da in the embodiments of the present invention is shown.

[0028] Figure 8 The image shows the ¹³C NMR spectrum of compound 3-4da in the embodiments of this invention.

[0029] Figure 9 The image shows the ³¹P NMR spectrum of compound 3-4da in the embodiments of the present invention.

[0030] Figure 10 The ¹H NMR spectrum of compound 3-4ea in the embodiments of the present invention is shown.

[0031] Figure 11 The image shows the ¹³C NMR spectrum of compound 3-4ea in the embodiments of the present invention.

[0032] Figure 12 The image shows the ³¹P NMR spectrum of compound 3-4ea in the embodiments of the present invention.

[0033] Figure 13 The ¹H NMR spectrum of compound 3-4fa in the embodiments of the present invention is shown.

[0034] Figure 14 The image shows the ¹³C NMR spectrum of compound 3-4fa in an embodiment of the present invention.

[0035] Figure 15 The image shows the ³¹P NMR spectrum of compound 3-4fa in an embodiment of the present invention.

[0036] Figure 16 The ¹H NMR spectrum of compound 3-4ga in the embodiments of the present invention is shown.

[0037] Figure 17 The image shows the ¹³C NMR spectrum of compound 3-4ga in an embodiment of the present invention.

[0038] Figure 18 The image shows the ³¹P NMR spectrum of compound 3-4ga in the embodiments of this invention.

[0039] Figure 19 The ¹H NMR spectrum of compound 3-4ha in the embodiments of the present invention is shown.

[0040] Figure 20 The image shows the ¹³C NMR spectrum of compound 3-4ha in an embodiment of the present invention.

[0041] Figure 21 The image shows the ³¹P NMR spectrum of compound 3-4ha in an embodiment of the present invention.

[0042] Figure 22 The ¹H NMR spectrum of compound 3-4ia in the embodiments of the present invention is shown.

[0043] Figure 23 The image shows the ¹³C NMR spectrum of compound 3-4ia in an embodiment of the present invention.

[0044] Figure 24 The image shows the ³¹P NMR spectrum of compound 3-4ia in an embodiment of the present invention.

[0045] Figure 25 The ¹H NMR spectrum of compound 3-4ja in the embodiments of the present invention is shown.

[0046] Figure 26 The image shows the ¹³C NMR spectrum of compound 3-4ja in an embodiment of the present invention.

[0047] Figure 27 The image shows the ³¹P NMR spectrum of compound 3-4ja in an embodiment of the present invention.

[0048] Figure 28 The ¹H NMR spectrum of compound 3-4ka in the embodiments of the present invention is shown.

[0049] Figure 29 The image shows the ¹³C NMR spectrum of compound 3-4ka in the embodiments of this invention.

[0050] Figure 30 The image shows the ³¹P NMR spectrum of compound 3-4ka in the embodiments of this invention. Detailed Implementation

[0051] The present invention will now be described in further detail with reference to the accompanying drawings and embodiments, but this does not limit the present invention in any way. Any modifications or improvements made based on the teachings of the present invention shall fall within the protection scope of the present invention.

[0052] The processes, conditions, reagents, and experimental methods used in implementing this invention, except as specifically mentioned below, are all common knowledge and general knowledge in the field, and this invention does not have any particular limitations. Experimental methods in the embodiments that do not specify specific conditions are generally performed under conventional conditions or as recommended by the manufacturer.

[0053] Unless otherwise stated, all technical terms and scientific terms used in this specification have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. However, in the event of any conflict, the specification containing the definitions shall prevail.

[0054] Example 1: Preparation of compound 3-4ba 0.5 mmol isocyanobenzene, 0.5 mmol diphenyldiselenes, 0.5 mmol O,O-diethyl thiophosphate, and 0.25 mmol iodosuccinimide (NIS, iodide catalyst) were sequentially added to 10 mL of ethanol (solvent), and the reaction was carried out at 60 °C for 24 h. After the reaction was complete (monitored by TLC), the reaction solution was cooled to room temperature, 20 mL of water was added, and the mixture was extracted with ethyl acetate (3 × 15 mL). The organic phases were combined, washed once with saturated brine, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 2:1) to give the target product 3-4ba in 68% (29.3 mg).

[0055] Its chemical structure was determined by mass spectrometry and nuclear magnetic resonance as follows:

[0056] Its NMR spectrum is shown in Figure 1-3 The data is attributed to the following: (Z)-(diethyl phosphoric) (Se-phenyl (Z)-phenylcarbonimidoselenoic)thioanhydride (3-4ba):yellow oil, yield: 68% (29.3mg). TLC (EA: PE=1:2): R f =0.19. 1H NMR (500 MHz, CDCl3) δ 7.54 – 7.46 (m, 5H), 7.46 – 7.41 (m, 3H), 7.41 – 7.36 (m, 2H), 4.27 – 4.19 (m, 2H), 4.07 (ddq, J = 9.9, 8.3, 7.0 Hz, 2H),1.21 (td, J = 7.1, 1.2 Hz, 6H). 13 C NMR (126 MHz, CDCl3) δ 204.6, 137.6, 129.9,129.9, 129.7, 129.7, 129.5, 129.5, 65.2 (d, J C-P = 6.3 Hz), 16.1 (d, J C-P = 7.3Hz). 31 P NMR (203 MHz, CDCl3) δ -4.6. HRMS (ESI) [M+H + ] Calcd For C 17 H 21 NO3PSSe + :430.0140, Found: 430.0144. Example 2: Preparation of compound 3-4ca 0.5 mmol of 1-isocyano-4-methylbenzene, 0.25 mmol of diphenyldiselenes, 0.5 mmol of O,O-diethyl thiophosphate, and 0.25 mmol of elemental iodine (I₂, iodide catalyst) were sequentially added to 6 mL of acetonitrile (solvent), and the reaction was carried out at 20 °C for 24 h. After the reaction was complete (monitored by TLC), the reaction solution was cooled to room temperature, 20 mL of water was added, and the mixture was extracted with ethyl acetate (3 × 15 mL). The organic phases were combined, washed once with saturated brine, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 2:1) to give the target product 3-4ba in 90% (39.8 mg).

[0057] Its chemical structure was determined by mass spectrometry and nuclear magnetic resonance as follows:

[0058] Its NMR spectrum is shown in Figure 4-6 The data is attributed to the following: (Z)-(diethyl phosphoric) (Se-phenyl (Z)-p-tolylcarbonimidoselenoic)thioanhydride (3-4ca):yellow oil, yield: 90% (39.8 mg). TLC (EA: PE=1:2): R f =0.20. 1 H NMR (500 MHz, CDCl3) δ 7.46 – 7.40 (m, 3H), 7.40 – 7.33 (m, 4H), 7.29(d, J = 8.0 Hz, 2H), 4.22 (dp, J = 10.0, 7.1 Hz, 2H), 4.13 – 4.03 (m, 2H), 2.44 (s, 3H), 1.22 (td, J = 7.1, 1.2 Hz, 6H). 13 C NMR (126 MHz, CDCl3) δ 204.8(d, J C-P = 5.8 Hz), 140.13 (d, J C-P = 1.6 Hz), 139.13 (d, J C-P = 4.0 Hz), 137.55,131.81, 130.0, 129.7, 129.4, 129.3, 129.3, 65.0 (d, J C-P = 6.4 Hz), 21.5, 16.0 (d, J C-P = 7.2 Hz). 31 P NMR (203 MHz, CDCl3) δ -4.4. HRMS (ESI) [M+H + ] Calcd ForC 18 H 23 NO3PSSe + : 444.0296, Found: 444.0209. Example 3 Preparation of compound 3-4da 0.5 mmol of 1-isocyano-4-methoxybenzene, 0.3 mmol of diphenyldiselenes, 0.5 mmol of O,O-diethyl thiophosphate, and 0.4 mmol of ammonium iodide (NH4I, iodide catalyst) were sequentially added to 6 mL of dichloromethane (solvent), and the reaction was carried out at 20 °C for 12 h. After the reaction was complete (monitored by TLC), the reaction solution was cooled to room temperature, 20 mL of water was added, and the mixture was extracted with ethyl acetate (3 × 15 mL). The organic phases were combined, washed once with saturated brine, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 2:1) to give the target product 3-4 da in 89% (41.0 mg).

[0059] Its chemical structure was determined by mass spectrometry and nuclear magnetic resonance as follows:

[0060] Its NMR spectrum is shown in Figure 7-9 The data is attributed to the following: (Z)-(diethyl phosphoric) (Se-phenyl (Z)-(4-methoxyphenyl)carbonimidoselenoic) thioanhydride (3-4da):yellow oil, yield: 89% (41.0 mg).TLC (EA: PE=1:1): R f = 0.23. 1 H NMR (500 MHz, CDCl3) δ 7.42 (td, J = 6.6, 1.5Hz, 3H), 7.40 – 7.35 (m, 4H), 7.01 – 6.96 (m, 2H), 4.22 (dp, J = 10.0, 7.1Hz, 2H), 4.12 – 4.03 (m, 2H), 3.86 (s, 3H), 1.22 (dd, J = 14.2, 1.2 Hz, 6H). 13 C NMR (126 MHz, CDCl3) δ 205.4 (d, J C-P = 6.3 Hz), 160.5, 137.5, 134.4,134.4, 131.9, 130.8, 130.8, 129.7, 129.4, 114.5, 65.0 (d, J C-P = 6.2 Hz), 55.6,16.1 (d, J C-P = 7.2 Hz).31 P NMR (203 MHz, CDCl3) δ -4.3. HRMS (ESI) [M+H + ] CalcdFor C 18 H 23 NO4PSSe + : 460.0245. Example 4 Preparation of compound 3-4ea 0.5 mmol of 1-isocyano-4-methoxybenzene, 0.5 mmol of diphenyldiselenes, 0.5 mmol of O,O-diethyl thiophosphate, and 0.4 mmol of tetramethylammonium iodide ((CH3)4NI, iodide catalyst) were sequentially added to 10 mL of N,N-dimethylformamide (solvent), and the reaction was carried out at 80 °C for 18 hours. After the reaction was complete (monitored by TLC), the reaction solution was cooled to room temperature, 20 mL of water was added, and the mixture was extracted with ethyl acetate (3 × 15 mL). The organic phases were combined, washed once with saturated brine, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 2:1) to give the target product 3-4ea in 62% (28.3 mg).

[0061] Its chemical structure was determined by mass spectrometry and nuclear magnetic resonance as follows:

[0062] Its NMR spectrum is shown in Figure 10-12 The data is attributed to the following: (Z)-(diethyl phosphoric) (Se-phenyl (Z)-(3,4-dimethylphenyl)carbonimidoselenoic) thioanhydride (3-4ea):yellow oil, yield: 62% (28.3 mg).TLC (EA: PE=1:2): R f = 0.24. 1 H NMR (500 MHz, CDCl3) δ 7.47 – 7.40 (m, 3H), 7.40– 7.35 (m, 2H), 7.26 – 7.18 (m, 3H), 4.23 (dp, J = 10.0, 7.1 Hz, 2H), 4.08(ddq, J = 10.0, 8.5, 7.1 Hz, 2H), 2.34 (s, 6H), 1.23 (td, J = 7.1, 1.1 Hz, 6H).13 C NMR (126 MHz, CDCl3) δ 204.9 (d, J C-P = 5.6 Hz), 139.3 (d, J C-P = 4.0 Hz),138.8, 138.0, 137.6, 132.0, 130.4, 130.4 (d, J C-P = 2.0 Hz), 129.7, 129.4,126.8 (d, J C-P = 2.0 Hz), 65.0 (d, J C-P = 6.1 Hz), 20.0, 19.8, 16.1 (d, J C-P = 7.2Hz). 31 P NMR (203 MHz, CDCl3) δ -4.4. HRMS (ESI) [M+H + ] Calcd For C 19 H 25 NO3PSSe + :458.0453, Found: 458.0457. Example 5: Preparation of compound 3-4fa 0.5 mmol 1-isocyano-4-bromobenzene, 0.3 mmol diphenyldiselenes, 0.4 mmol O,O-diethyl thiophosphate, and 0.3 mmol tetrabutylammonium iodide (( n -Bu)4NI (iodide catalyst) was added sequentially to 8 mL of N,N-dimethylacetamide (solvent), and the reaction was carried out at 60 °C for 18 hours. After the reaction was complete (monitored by TLC), the reaction solution was cooled to room temperature, 20 mL of water was added, and the mixture was extracted with ethyl acetate (3 × 15 mL). The organic phases were combined, washed once with saturated brine, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 2:1) to give the target product 3-4fa in 51% (25.9 mg).

[0063] Its chemical structure was determined by mass spectrometry and nuclear magnetic resonance as follows:

[0064] Its NMR spectrum is shown in Figure 13-15 The data is attributed to the following: (Z)-(diethyl phosphoric) (Se-phenyl (Z)-(4-bromophenyl)carbonimidoselenoic) thioanhydride (3-4fa):yellow oil, yield: 51% (25.9 mg).TLC (EA: PE=1:2): R f = 0.19. 1 H NMR (500 MHz, CDCl3) δ 7.66 – 7.59 (m, 2H), 7.46– 7.37 (m, 5H), 7.36 – 7.30 (m, 2H), 4.24 (qd, J = 7.2, 2.8 Hz, 2H), 4.15 –4.07 (m, 2H), 1.25 (td, J = 7.0, 1.2 Hz, 6H). 13 C NMR (126 MHz, CDCl3) δ 204.1(d, J C-P = 5.1 Hz), 140.8 (d, J C-P = 4.1 Hz), 137.6, 132.7, 131.6, 131.3, 131.3,129.0, 130.58, 124.1 (d, J C-P = 1.8 Hz), 65.3 (d, J C-P = 6.3 Hz), 16.1 (d, J C-P =7.0 Hz). 31 P NMR (203 MHz, CDCl3) δ -4.7. HRMS (ESI) [M+H + ] Calcd ForC 17 H 20 BrNO3PSSe + Found: 507.9245, Found: 507.9248. Example 6 Preparation of compound 3-4ga 0.5 mmol of 1-isocyano-4-fluorobenzene, 0.5 mmol of diphenyldiselenes, 0.4 mmol of O,O-diethyl thiophosphate, and 0.2 mmol of sodium iodide (NaI, iodide catalyst) were sequentially added to 10 mL of dimethyl sulfoxide (solvent), and the reaction was carried out at 60 °C for 18 hours. After the reaction was complete (monitored by TLC), the reaction solution was cooled to room temperature, 20 mL of water was added, and the mixture was extracted with ethyl acetate (3 × 15 mL). The organic phases were combined, washed once with saturated brine, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 2:1) to give the target product 3-4ga in 68% (30.7 mg).

[0065] Its chemical structure was determined by mass spectrometry and nuclear magnetic resonance as follows:

[0066] Its NMR spectrum is shown in Figure 16-18 The data is attributed to the following: (Z)-(diethyl phosphoric) (Se-phenyl (Z)-(4-fluorophenyl)carbonimidoselenoic) thioanhydride (3-4ga): yellow oil, yield: 68% (30.7 mg).TLC (EA: PE=1:2): R f = 0.19. 1 H NMR (500 MHz, CDCl3) δ 7.49 – 7.41 (m, 5H), 7.41 – 7.37 (m, 2H), 7.21 – 7.15 (m, 2H), 4.27 – 4.20 (m, 2H), 4.14 – 4.05 (m,2H), 1.24 (td, J = 7.0, 1.2 Hz, 6H). 13 C NMR (126 MHz, CDCl3) δ 204.6 (d, J C-P =5.4 Hz), 164.1, 162.1, 137.7 (t, J C-F = 3.7 Hz), 137.5, 131.7 – 131.6 (m),131.5 (d, J C-F = 2.0 Hz), 129.9, 129.5, 116.5, 116.4, 65.2 (d, J C-P = 6.1 Hz), 16.1 (d, JC-P = 7.2 Hz). 31 P NMR (203 MHz, CDCl3) δ -4.5. HRMS (ESI) [M+H + ] CalcdFor C 17 H 20 FNO3PSSe + Found: 448.0045, Found: 448.0049. Example 7 Preparation of compound 3-4ha 0.5 mmol of 1-isocyano-4-fluorobenzene, 0.3 mmol of diphenyldiselenes, 0.5 mmol of O,O-diethyl thiophosphate, and 0.4 mmol of potassium iodide (KI, iodide catalyst) were sequentially added to 10 mL of tetrahydrofuran (solvent), and the reaction was carried out at 40 °C for 24 hours. After the reaction was complete (monitored by TLC), the reaction solution was cooled to room temperature, 20 mL of water was added, and the mixture was extracted with ethyl acetate (3 × 15 mL). The organic phases were combined, washed once with saturated brine, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 3:1) to give the target product 3-4 ha in 57% (26.6 mg).

[0067] Its chemical structure was determined by mass spectrometry and nuclear magnetic resonance as follows:

[0068] Its NMR spectrum is shown in Figure 19-21 The data is attributed to the following: (Z)-(diethyl phosphoric) (Se-phenyl (Z)-(4-chlorophenyl)carbonimidoselenoic) thioanhydride (3-4ha): yellow oil, yield: 57% (26.6 mg).TLC (EA: PE=1:2): R f = 0.23. 1 H NMR (500 MHz, CDCl3) δ 7.48 – 7.45 (m, 2H), 7.42(t, J = 7.4 Hz, 4H), 7.39 (t, J = 7.4 Hz, 3H), 4.28 – 4.20 (m, 2H), 4.14 –4.06 (m, 2H), 1.25 (td, J = 7.1, 1.1 Hz, 6H). 13C NMR (126 MHz, CDCl3) δ 204.2(d, J C-P = 5.3 Hz), 140.3 (d, J C-P = 4.1 Hz), 137.6, 135.9 (d, J C-P = 1.7 Hz),131.6, 131.0, 130.9, 129.9, 129.7, 129.6, 65.2 (d, J C-P = 6.1 Hz), 16.1 (d, J C-P = 7.1 Hz). 31 P NMR (203 MHz, CDCl3) δ -4.6. HRMS (ESI) [M+H + ] Calcd ForC 17 H 20 ClNO3PSSe + Found: 463.9750, Found: 463.9755. Example 8 Preparation of compound 3-4ia 0.5 mmol of 1-isocyano-4-iodobenzene, 0.3 mmol of diphenyldiselenes, 0.5 mmol of O,O-diethylthiophosphate, and 0.4 mmol of iodosuccinimide (NIS, iodide catalyst) were sequentially added to 4 mL of dioxane (solvent), and the reaction was carried out at 80 °C for 24 hours. After the reaction was complete (monitored by TLC), the reaction solution was cooled to room temperature, 20 mL of water was added, and the mixture was extracted with ethyl acetate (3 × 15 mL). The organic phases were combined, washed once with saturated brine, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 2:1) to give the target product 3-4ia in 48% (26.8 mg). The chemical structure was identified by mass spectrometry and NMR as follows:

[0069] Its NMR spectrum is shown in Figure 22-24 The data is attributed to the following: (Z)-(diethyl phosphoric) (Se-phenyl (Z)-(4-iodophenyl)carbonimidoselenoic) thioanhydride (3-4ia): yellow oil, yield: 48% (26.8 mg).TLC (EA: PE=1:2): R f = 0.19.1 H NMR (500 MHz, CDCl3) δ 7.85 – 7.81 (m, 2H), 7.46– 7.38 (m, 5H), 7.22 – 7.18 (m, 2H), 4.24 (dq, J = 10.0, 7.2 Hz, 2H), 4.10(dtd, J = 10.0, 7.1, 2.1 Hz, 2H), 1.25 (td, J = 7.0, 1.1 Hz, 6H). 13 C NMR (126MHz, CDCl3) δ 204.0 (d, J C-P = 5.4 Hz), 141.6 (d, J C-P = 3.9 Hz), 138.8, 137.6,131.6, 131.5, 131.4, 130.0, 129.6, 95.8 (d, J C-P = 1.9 Hz), 65.3 (d, J C-P = 6.2Hz), 16.1 (d, J C-P = 7.1 Hz). 31 P NMR (203 MHz, CDCl3) δ -4.7. HRMS (ESI) [M+H + ]Calcd For C 17 H 20 INO3PSSe + Found: 555.9106, Found: 555.9109. Example 9 Preparation of compound 3-4ja 0.5 mmol of 1-isocyano-4-trifluoromethylbenzene, 0.4 mmol of diphenyldiselenes, 0.4 mmol of O,O-diethylthiophosphate, and 0.5 mmol of iodosuccinimide (NIS, iodide catalyst) were sequentially added to 8 mL of 1,2-dichloroethane (solvent), and the reaction was carried out at 20 °C for 6 hours. After the reaction was complete (monitored by TLC), the reaction solution was cooled to room temperature, 20 mL of water was added, and the mixture was extracted with ethyl acetate (3 × 15 mL). The organic phases were combined, washed once with saturated brine, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 2:1) to give the target product 3-4ja in 60% (29.8 mg). The chemical structure was identified by mass spectrometry and NMR as follows:

[0070] Its NMR spectrum is shown in Figure 25-27 The data is attributed to the following: (Z)-(diethyl phosphoric) (Se-phenyl (Z)-(4-(trifluoromethyl)phenyl)carbonimidoselenoic) thioanhydride (3-4ja):yellow oil, yield: 60% (29.8 mg).TLC (EA: PE=1:2): R f = 0.19. 1 H NMR (500 MHz, CDCl3) δ 7.76 (d, J = 8.3 Hz, 2H), 7.59 (d, J = 8.2 Hz, 2H), 7.50 – 7.35 (m, 5H), 4.26 (dq, J = 10.0, 7.2 Hz, 2H), 4.17 – 4.10 (m, 2H), 1.26 (t, J = 7.1 Hz, 6H). 13 C NMR (126 MHz, CDCl3) δ203.7 (d, J C-P = 5.0 Hz), 145.9, 137.6, 131.5, 130.3, 130.3, 130.1, 129.6,126.6 (d, J C-F = 4.0 Hz), 124.8, 122.7, 65.4 (d, J C-P = 6.2 Hz), 16.1 (d, J C-P =7.1 Hz). 31 P NMR (203 MHz, CDCl3) δ -4.8. HRMS (ESI) [M+H + ] Calcd ForC 18 H 20 F3NO3PSSe + Found: 498.0013, Found: 498.0017. Example 10 Preparation of compound 3-4ka 0.5 mmol of 1-isocyano-4-acetylbenzene, 0.3 mmol of diphenyldiselenoether, 0.5 mmol of O,O-diethyl thiophosphate, and 0.3 mmol of elemental iodine (I₂, iodide catalyst) were sequentially added to 10 mL of chloroform (solvent), and the reaction was carried out at 40 °C for 12 h. After the reaction was complete (monitored by TLC), the reaction solution was cooled to room temperature, 20 mL of water was added, and the mixture was extracted with ethyl acetate (3 × 15 mL). The organic phases were combined, washed once with saturated brine, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 4:1) to give the target product 3-4 kDa, with a yield of 60% (28.2 mg). The chemical structure was identified by mass spectrometry and NMR as follows:

[0071] Its NMR spectrum is shown in Figures 28-30 The data is attributed to the following: (Z)-(diethyl phosphoric) (Se-phenyl (Z)-(4-acetylphenyl)carbonimidoselenoic) thioanhydride (3-4ka): yellow oil, yield: 60% (28.2 mg).TLC (EA: PE=1:1): R f = 0.24. 1 H NMR (500 MHz, CDCl3) δ 8.10 – 8.06 (m, 2H), 7.56(d, J = 7.4 Hz, 2H), 7.46 – 7.37 (m, 5H), 4.29 – 4.22 (m, 2H), 4.17 – 4.09(m, 2H), 2.66 (s, 3H), 1.25 (td, J = 7.0, 1.1 Hz, 6H). 13 C NMR (126 MHz, CDCl3)δ 203.7 (d, J C-P = 4.9 Hz), 197.0, 145.9 (d, J C-P = 3.9 Hz), 137.6, 131.5, 130.1,130.0, 129.9, 129.6, 129.5, 65.3 (d, J C-P = 6.3 Hz), 26.9, 16.1 (d, J C-P = 7.1Hz). 31P NMR (203 MHz, CDCl3) δ -4.8. HRMS (ESI) [M+H + ] Calcd For C 19 H 23 NO4PSSe + :472.0245, Found: 472.0245. Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for preparing an arylselenide thiophosphate compound, characterized in that, Includes the following steps: The isonitrile, diaryl diselenide, O,O-dialkyl thiophosphate and iodide catalyst are added sequentially to the solvent and reacted at 0~80℃ to obtain the product.

2. The preparation method according to claim 1, characterized in that, The iodide is any one of iodosuccinimide, iodine, ammonium iodide, sodium iodide, potassium iodide, tetramethylammonium iodide, and tetrabutylammonium iodide.

3. The preparation method according to claim 1, characterized in that, The isonitriles are any one of isocyanobenzene, 1-isocyano-4-methylbenzene, 1-isocyano-3-methylbenzene, 1-isocyano-2-methylbenzene, 1-isocyano-4-methoxybenzene, 1-isocyano-3-methoxybenzene, 1-isocyano-2-methoxybenzene, 1-isocyano-4-trifluoromethylbenzene, 1-isocyano-4-fluorobenzene, 1-isocyano-4-chlorobenzene, 1-isocyano-4-bromobenzene, 1-isocyano-4-iodobenzene, 1-isocyano-4-tert-butylbenzene, 1-isocyano-4-ethylbenzene, 1-isocyano-4-isopropylbenzene, 1-isocyano-4-nitrobenzene, isocyanoethane, isocyanopropane, and tert-butylisocyanates.

4. The preparation method according to claim 1, characterized in that, The diaryl diselenide is any one of diphenyl diselenide, di(4-methylphenyl)diselenide, di(3-methylphenyl)diselenide, di(2-methylphenyl)diselenide, di(4-methoxyphenyl)diselenide, di(4-ethylphenyl)diselenide, di(4-tert-butylphenyl)diselenide, di(4-isopropylphenyl)diselenide, di(4-fluorophenyl)diselenide, di(4-chlorophenyl)diselenide, di(4-bromophenyl)diselenide, di(4-iodophenyl)diselenide, di(2-furanyl)diselenide, and di(2-thiophenyl)diselenide.

5. The preparation method according to claim 1, characterized in that, The O,O-dialkyl thiophosphate is any one of O,O-dimethyl thiophosphate, O,O-diethyl thiophosphate, O,O-dipropyl thiophosphate, O,O-diisopropyl thiophosphate, O,O-di-tert-butyl thiophosphate, O,O-di-sec-butyl thiophosphate, O,O-di-tert-butyl thiophosphate, and O,O-dibenzyl thiophosphate.

6. The preparation method according to claim 1, characterized in that, The solvent is any one of N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile, toluene, tetrahydrofuran, 1,4-dioxane, 1,2-dichloroethane, dimethyl sulfoxide, methanol, ethanol, dichloromethane, chloroform, and ethyl acetate.

7. The preparation method according to claim 1, characterized in that, The molar ratio of the iodide catalyst to the isonitrile is 0.1~1.0:1; the molar ratio of the diaryl diselenyl ether to the isonitrile is 0.1~1.2:1; the molar ratio of the O,O-dialkyl thiophosphate to the isonitrile is 0.1~1.0:1; and the molar ratio of the isonitrile to the solvent is 1:50~200.

8. The preparation method according to claim 1, characterized in that, It also includes steps of extraction, drying, concentration, and column chromatography separation of the obtained reaction solution.

9. The preparation method according to claim 1, characterized in that, The reaction time is 12-24 hours.

10. The preparation method according to claim 1, characterized in that, The aryl selenide thiophosphate compound is selected from at least one of the following formulas: 3-4ba, 3-4ca, 3-4da, 3-4ea, 3-4fa, 3-4ga, 3-4ha, 3-4ia, 3-4ja, 3-4ka. 。

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