Method for constructing C-P bond based on halogenated pyrrolo [1, 2-a] quinoxaline

Abstract

The invention belongs to the technical field of organic synthesis, and particularly relates to a method for constructing a C-P bond based on halogenated pyrrolo [1, 2-a] quinoxaline, which comprises the following steps: mixing halogenated pyrrolo [1, 2-a] quinoxaline and phosphite ester in a solvent under the irradiation of visible light, and stirring and reacting at room temperature to obtain phosphonate of nitrogen-containing fused heterocyclic aromatic hydrocarbon and a derivative thereof. According to the invention, on the basis of halogenated nitrogen-containing fused heterocyclic aromatic hydrocarbon, the phosphating reaction without participation of a photocatalyst and an additive is completed through visible light induction, and a new efficient, simple, convenient and environment-friendly nitrogen-containing fused heterocyclic aromatic hydrocarbon functionalization strategy is established. According to the present invention, the research on the regioselective functionalization reaction can be completed through the difference of the halogenation sites, such that the generation of the by-product is substantially reduced so as to improve the yield of the target product, and the expansibility is increased through the wide halogenation of the nitrogen-containing fused heterocyclic aromatic hydrocarbon substrate. And a novel method is provided for transformation and modification of specific sites of the nitrogen-containing fused heterocyclic aromatic hydrocarbon.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic synthesis, and particularly relates to a method for constructing C-P bonds based on halogenated pyrrolo[1,2-a]quinoxaline. Background Art

[0002] Aryl phosphonates are widely present in various compounds, including pharmaceuticals, agrochemicals, and ligands for metal catalysis. Therefore, it is very necessary to develop an efficient, green, and mild photochemical method to promote the construction of C-P bonds in heteroaromatic hydrocarbons.

[0003] In past research, some teams used a photoredox pathway to generate aryl phosphate compounds from aryl halides using rare metal photocatalysts or organic dyes. However, these methods usually rely on expensive photocatalysts and additives. Therefore, catalyst-free photoinduced phosphonation has received more attention due to its environmental friendliness and mild reaction conditions. However, these methods usually also require the use of dangerous ultraviolet radiation, which limits scalability and widespread adoption.

[0004] In recent years, reports have pointed out that organic bases (t-BuOK, t-BuONa) or K2CO3 are used to form an EDA complex with aryl halides, or a strong base compound NaH is used to dehydrogenate solvents such as DMF or MeCN and then form an EDA complex with aryl compounds, and then aryl radicals are formed to participate in the construction of C-P bonds. Although these methods have improved the environmental friendliness of phosphonation to a certain extent, they have also introduced additives such as basic substances or inorganic substances, and there are still certain limitations.

[0005] The present method uses halogenated pyrrolo[1,2-a]quinoxaline as a substrate, and on the basis of not using a photocatalyst and additives, through a photocatalytic EDA reaction mechanism, a new strategy for regioselectively constructing C-P bonds is obtained. Summary of the Invention

[0006] The purpose of the present invention is to provide a method for constructing C-P bonds based on halogenated pyrrolo[1,2-a]quinoxaline. This method completes a phosphonation reaction without the participation of a photocatalyst and additives through visible light induction, generates high-energy radical intermediates in a mild manner, and establishes a new strategy for the functionalization of nitrogen-containing fused heteroaromatic hydrocarbons that is efficient, simple, and environmentally friendly.

[0007] The purpose of the present invention is achieved by the following technical solutions:

[0008] The present invention provides a method for constructing C-P bonds based on halogenated pyrrolo[1,2-a]quinoxaline, and the method includes the following steps:

[0009] Under visible light irradiation, a halogenated pyrrolo[1,2-a]quinoxaline and a phosphite are mixed in a solvent and stirred at room temperature to obtain a phosphonate ester of a nitrogen-containing fused heterocyclic aromatic hydrocarbon and its derivatives.

[0010] Further, the reaction general formula is:

[0011]

[0012] Among them, R 1 is a substituent at the 7- or 8-position on the benzene ring;

[0013] R 2 is 4-phenyl, 4-NO2 phenyl or 4-OMe group;

[0014] R 3 is Me, i Pr or n Bu.

[0015] Further, the R 1 is selected from H, Me or Cl.

[0016] Further, the wavelength of the visible light is 390 nm, and the solvent is selected from dichloromethane or acetonitrile.

[0017] Further, the molar ratio of the halogenated pyrrolo[1,2-a]quinoxaline to the phosphite is 1:10.

[0018] Further, the reaction time is 3 - 12 hours, and the reaction is carried out in an inert gas atmosphere.

[0019] Further, the method further includes a step of purifying the obtained phosphonate ester of the nitrogen-containing fused heterocyclic aromatic hydrocarbon and its derivatives.

[0020] The present invention also provides a phosphonate ester of a nitrogen-containing fused heterocyclic aromatic hydrocarbon and its derivatives prepared by the described method.

[0021] Further, the phosphonate esters of the nitrogen-containing fused heterocyclic aromatic hydrocarbons include 1-(pyrrolo[1,2-a]quinoxalin-1-yl)diethyl phosphonate and 3-(pyrrolo[1,2-a]quinoxalin-3-yl)diethyl phosphonate.

[0022] The present invention also provides the application of the phosphonate ester of the nitrogen-containing fused heterocyclic aromatic hydrocarbon and its derivatives in the fields of drug synthesis, materials science or catalysis.

[0023] The beneficial effects of the present invention are as follows:

[0024] 1. Based on halogenated nitrogen-containing fused heteroaromatic hydrocarbons, through visible light induction, a phosphination reaction without a photocatalyst and additives is completed, generating high-energy radical intermediates in a mild manner, and establishing a new strategy for the functionalization of nitrogen-containing fused heteroaromatic hydrocarbons that is efficient, simple, and environmentally friendly.

[0025] 2. The research on regioselective functionalization reactions can be completed through different halogenation sites, greatly reducing the generation of by-products, thereby increasing the yield of the target product, and increasing the expandability through a wide range of halogenated nitrogen-containing fused heteroaromatic hydrocarbon substrates. It provides a new method for the modification and decoration of specific sites of nitrogen-containing fused heteroaromatic hydrocarbons. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required for use in the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can be obtained based on these drawings.

[0027] Figure 1 It is a diagram showing the distribution results of the molecular orbitals of the EDA complex simulated by DFT calculation in the present invention;

[0028] Figure 2 It is the ultraviolet-visible absorption spectrum diagram of halogenated pyrrolo[1,2-a]quinoxaline and triethyl phosphite in the present invention;

[0029] Figure 3 It is the NMR spectrum diagram of 1-(pyrrolo[1,2-a]quinoxalin-1-yl)diethylphosphonate prepared in the present invention. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0030] The following details the embodiments of the present invention. The embodiments are intended to explain the present invention and should not be construed as limiting the present invention. For those technical or conditions not specified in the embodiments, they shall be carried out according to the techniques or conditions described in the literature in the field or according to the product specifications. The reagents or instruments not specified by the manufacturer can be obtained as conventional products through commercial purchase.

[0031] In the present invention, a method for preparing 1-(pyrrolo[1,2-a]quinoxalin-1-yl)diethylphosphonate or 3-(pyrrolo[1,2-a]quinoxalin-3-yl)diethylphosphonate and its derivatives using 390 nm purple light as the light source and halogenated pyrrolo[1,2-a]quinoxaline and triethyl phosphite as reactants, the steps are as follows:

[0032] React with halopyrrolo[1,2-a]quinoxaline, triethyl phosphite, and a solvent in a side-arm quartz tube. Stir the mixture at 30 °C under argon protection for 3 - 12 hours. After the reaction is complete, add dichloromethane for dilution and transfer the crude reaction product, then remove the solvent under reduced pressure. Purify the crude product by flash chromatography on silica gel to obtain the final product 1-(pyrrolo[1,2-a]quinoxalin-1-yl)diethyl phosphate or 3-(pyrrolo[1,2-a]quinoxalin-3-yl)diethyl phosphate and its derivatives.

[0033] The structure of the triethyl phosphite described above is as follows:

[0034]

[0035] The solvent is DCM or MeCN;

[0036] The reaction general formula for the phosphorylation reaction of halopyrrolo[1,2-a]quinoxaline is as follows:

[0037]

[0038] In the formula, R 1 is a substituent at the 7- or 8-position on the benzene ring, selected from the following groups (one of): H, Me, Cl;

[0039] R 2 is 4-phenyl, 4-NO2 phenyl, 4-OMe group;

[0040] R 3 is Me, i Pr, n Bu;

[0041] Furthermore, the molar ratio of the halopyrrolo[1,2-a]quinoxaline to the triethyl phosphite is 1:10;

[0042] Furthermore, the reaction temperature is room temperature, the solvent dosage is 1 mL, and the time is 3 - 12 h.

[0043] Among them, the distribution result diagram of the molecular orbitals of the EDA complex simulated by DFT calculation is as shown in Figure 1 shown, and the ultraviolet-visible absorption spectra of halopyrrolo[1,2-a]quinoxaline and triethyl phosphite are as shown in Figure 2 shown. In order to have a clearer understanding of the technical features, objectives, and effects of the present invention, the specific embodiments of the present invention are now described.

[0044] Example 1 Synthesis of 1-(pyrrolo[1,2-a]quinoxalin-1-yl)diethyl phosphate

[0045] In this example, the specific synthesis steps of 1-(pyrrolo[1,2-a]quinoxalin-1-yl)diethyl phosphonate are as follows:

[0046] Charge 1-iodopyrrolo[1,2-a]quinoxaline (0.1 mmol, 0.0294 g) into a 10 mL three-necked quartz reaction tube. Under argon protection, add triethyl phosphite (1.0 mmol, 0.1662 g) and a solvent (1 mL). Stir the mixture for 3 h at room temperature under a light source with a wavelength of 390 nm. After the reaction is completed, remove the solvent under reduced pressure. Finally, purify the crude product by flash column chromatography on silica gel (petroleum ether / ethyl acetate = 2:1) to obtain 29.2 mg of the final product 1-(pyrrolo[1,2-a]quinoxalin-1-yl)diethyl phosphonate, with a yield of 96%. The NMR spectrum of the obtained 1-(pyrrolo[1,2-a]quinoxalin-1-yl)diethyl phosphonate is as Figure 3 shown. The reaction formula is as follows:

[0047]

[0048] 1-(pyrrolo[1,2-a]quinoxalin-1-yl)diethyl phosphonate: 1 H NMR (400 MHz, CDCl3) δ 9.02 - 8.79 (m, 2H), 8.02 (dd, J = 8.0, 1.6 Hz, 1H), 7.65 - 7.57 (m, 1H), 7.57 - 7.49 (m, 2H), 6.94 (dd, J = 4.0, 2.8 Hz, 1H), 4.30 - 4.13 (m, 4H), 1.33 (t, J = 7.0 Hz, 6H). 13 C NMR (101

[0049] MHz, CDCl3) δ 145.57, 136.90, 132.20 (d, J = 10.4 Hz), 130.30, 129.13, 128.46, 12

[0050] 7.78 (d, J = 15.8 Hz), 126.17, 117.99, 117.85 (d, J = 222.6 Hz), 107.38 (d, J = 12.7 Hz), 63.32 (d, J = 5.6 Hz), 16.36 (d, J = 6.5 Hz). 31 P NMR (162 MHz, CDCl3) δ 9.68.

[0051] Synthesis of 1-(pyrrolo[1,2-a]quinoxalin-1-yl)diethyl phosphonate in Example 2

[0052] In this example, the specific synthesis steps of 1-(pyrrolo[1,2-a]quinoxalin-1-yl)diethyl phosphonate are as follows:

[0053] Charge 1-bromopyrrolo[1,2-a]quinoxaline (0.1 mmol, 0.0247 g) into a 10 mL three-necked quartz reaction tube. Under argon protection, add triethyl phosphite (1.0 mmol, 0.1662 g) and a solvent (1 mL). Stir the mixture at room temperature under a light source with a wavelength of 390 nm for 5 h. After the reaction is completed, remove the solvent under reduced pressure. Finally, purify the crude product by flash column chromatography on silica gel (petroleum ether / ethyl acetate = 2:1) to obtain 19.1 mg of the final product 1-(pyrrolo[1,2-a]quinoxalin-1-yl)diethyl phosphate, with a yield of 63%. The reaction formula is as follows:

[0054]

[0055] 1-(pyrrolo[1,2-a]quinoxalin-1-yl)diethyl phosphate: 1 H NMR (400 MHz, CDCl3) δ 9.02 - 8.79 (m, 2H), 8.02 (dd, J = 8.0, 1.6 Hz, 1H), 7.65 - 7.57 (m, 1H), 7.57 - 7.49 (m, 2H), 6.94 (dd, J = 4.0, 2.8 Hz, 1H), 4.30 - 4.13 (m, 4H), 1.33 (t, J = 7.0 Hz, 6H). 13 C NMR (101

[0056] MHz, CDCl3) δ 145.57, 136.90, 132.20 (d, J = 10.4 Hz), 130.30, 129.13, 128.46, 12

[0057] 7.78 (d, J = 15.8 Hz), 126.17, 117.99, 117.85 (d, J = 222.6 Hz), 107.38 (d, J = 12.7 Hz), 63.32 (d, J = 5.6 Hz), 16.36 (d, J = 6.5 Hz). 31 P NMR (162 MHz, CDCl3) δ 9.68.

[0058] Example 3 Synthesis of 1-(pyrrolo[1,2-a]quinoxalin-1-yl)diethyl phosphate

[0059] In this example, the specific synthesis steps of 1-(pyrrolo[1,2-a]quinoxalin-1-yl)diethyl phosphonate are as follows: Charge 1-chloropyrrolo[1,2-a]quinoxaline (0.1 mmol, 0.0203 g) into a 10 mL three-necked quartz reaction tube. Under argon protection, add triethyl phosphite (1.0 mmol, 0.1662 g) and a solvent (1 mL). Stir the mixture at room temperature under a light source with a wavelength of 390 nm for 12 h. After the reaction is completed, remove the solvent under reduced pressure. Finally, purify the crude product by silica gel flash chromatography (petroleum ether / ethyl acetate = 2:1) to obtain the final product 1-(pyrrolo[1,2-a]quinoxalin-1-yl)diethyl phosphonate, 26.7 mg, with a yield of 88%. The reaction formula is as follows:

[0060]

[0061] 1-(pyrrolo[1,2-a]quinoxalin-1-yl)diethyl phosphonate: 1 H NMR (400 MHz, CDCl3) δ 9.02 - 8.79 (m, 2H), 8.02 (dd, J = 8.0, 1.6 Hz, 1H), 7.65 - 7.57 (m, 1H), 7.57 - 7.49 (m, 2H), 6.94 (dd, J = 4.0, 2.8 Hz, 1H), 4.30 - 4.13 (m, 4H), 1.33 (t, J = 7.0 Hz, 6H). 13 C NMR (101

[0062] MHz, CDCl3) δ 145.57, 136.90, 132.20 (d, J = 10.4 Hz), 130.30, 129.13, 128.46, 12

[0063] 7.78 (d, J = 15.8 Hz), 126.17, 117.99, 117.85 (d, J = 222.6 Hz), 107.38 (d, J = 12.7 Hz), 63.32 (d, J = 5.6 Hz), 16.36 (d, J = 6.5 Hz). 31 P NMR (162 MHz, CDCl3) δ 9.68.

[0064] Synthesis of Example 4 3-(pyrrolo[1,2-a]quinoxalin-3-yl)diethyl phosphonate

[0065] In this example, the specific synthesis steps of 3-(pyrrolo[1,2-a]quinoxalin-3-yl)diethyl phosphonate are as follows: Charge 3-iodopyrrolo[1,2-a]quinoxaline (0.1 mmol, 0.0294 g) into a 10 mL branched quartz reaction tube. Under argon protection, add triethyl phosphite (1.0 mmol, 0.1662 g) and a solvent (1 mL). Stir the mixture at room temperature under a light source with a wavelength of 390 nm for 6 h. After the reaction is completed, remove the solvent under reduced pressure. Finally, purify the crude product by flash silica gel chromatography (petroleum ether / ethyl acetate = 1:1) to obtain 20.6 mg of the final product 3-(pyrrolo[1,2-a]quinoxalin-3-yl)diethyl phosphonate, with a yield of 68%. The reaction formula is as follows:

[0066]

[0067] 3-(pyrrolo[1,2-a]quinoxalin-3-yl)diethyl phosphonate: 1 H NMR (400 MHz, CDCl3) δ 9.32 (s, 1H), 8.05 (d, J = 7.6 Hz, 1H), 7.97 (d, J = 3.2 Hz, 1H), 7.90 (d, J = 8.4 Hz, 1H), 7.59 (t, J = 7.6 Hz, 1H), 7.56 - 7.50 (m, 1H), 7.21 - 7.17 (m, 1H), 4.19 (dt, J = 10.0, 7.4 Hz, 2H), 4.15 - 4.07 (m, 2H), 1.33 (t, J = 7.2 Hz, 6H). 13 C NMR (101 MHz, CDCl3) δ 145.28, 136.03, 130.51, 128.94 (d, J = 25.2 Hz), 128.74, 127.25, 126.29, 118.40 (d, J = 11.3 Hz), 114.81 (d, J = 14.7 Hz), 114.28 (d, J = 1.4 Hz), 106.06 (d, J = 217.5 Hz), 62.14 (d, J = 5.2 Hz), 16.40 (d, J = 6.8 Hz). 31 P NMR (162 MHz, CDCl3) δ 14.27.

[0068] Synthesis of 3-(pyrrolo[1,2-a]quinoxalin-3-yl)diethyl phosphonate in Example 5

[0069] In this example, the specific synthesis steps of 3-(pyrrolo[1,2-a]quinoxalin-3-yl)diethyl phosphonate are as follows: Charge 3-bromopyrrolo[1,2-a]quinoxaline (0.1 mmol, 0.0247 g) into a 10 mL three-necked quartz reaction tube. Under argon protection, add triethyl phosphite (1.0 mmol, 0.1662 g) and a solvent (1 mL). Stir the mixture at room temperature under a light source with a wavelength of 390 nm for 24 h. After the reaction is completed, remove the solvent under reduced pressure. Finally, purify the crude product by flash column chromatography on silica gel (petroleum ether / ethyl acetate = 1:1) to obtain 12.5 mg of the final product 3-(pyrrolo[1,2-a]quinoxalin-3-yl)diethyl phosphonate, with a yield of 41%. The reaction formula is as follows:

[0070]

[0071] 3-(pyrrolo[1,2-a]quinoxalin-3-yl)diethyl phosphonate: 1 H NMR(400MHz,CDCl3)δ9.32(s,1H),8.05(d,J=7.6Hz,1H),7.97(d,J=3.2Hz,1H),7.90(d,J=8.4Hz,1H),7.59(t,J=7.6Hz,1H),7.56-7.50(m,1H),7.21-7.17(m,1H),4.19(dt,J=10.0,7.4Hz,2H),4.15-4.07(m,2H),1.33(t,J=7.2Hz,6H). 13 C NMR(101MHz,CDCl3)δ145.28,136.03,130.51,128.94(d,J=25.2Hz),128.74,127.25,126.29,118.40(d,J=11.3Hz),114.81(d,J=14.7Hz),114.28(d,J=1.4Hz),106.06(d,J=217.5Hz),62.14(d,J=5.2Hz),16.40(d,J=6.8Hz). 31 P NMR(162MHz,CDCl3)δ14.27.

[0072] Synthesis of diethyl (4-phenylpyrrolo[1,2-a]quinoxalin-1-yl)phosphate in Example 6

[0073] The specific synthesis steps of diethyl (4-phenylpyrrolo[1,2-a]quinoxalin-1-yl)phosphate in this example are as follows: Charge 1-iodo-4-phenylpyrrolo[1,2-a]quinoxaline (0.1 mmol, 0.0370 g) into a 10 mL three-necked quartz reaction tube. Under argon protection, add triethyl phosphite (1.0 mmol, 0.1662 g) and a solvent (1 mL). Stir the mixture at room temperature under a light source with a wavelength of 390 nm for 6 h. After the reaction is completed, remove the solvent under reduced pressure. Finally, purify the crude product by silica gel flash chromatography (petroleum ether / ethyl acetate = 3:1) to obtain 34.7 mg of the final product diethyl (4-phenylpyrrolo[1,2-a]quinoxalin-1-yl)phosphate, with a yield of 92%. The reaction formula is as follows:

[0074]

[0075] diethyl (4-phenylpyrrolo[1,2-a]quinoxalin-1-yl)phosphate 1 H NMR(400MHz,CDCl3)δ8.95(dd,J=8.4,1.2Hz,1H),8.10(dd,J=8.0,1.7Hz,1H),8.01-7.89(m,2H),7.65-7.49(m,6H),7.01(dd,J=4.3,3.1Hz,1H),4.32-4.15(m,4H),1.35(t,J=7.2Hz,6H). 13 C NMR(101MHz,CDCl3)δ154.45(d,J=1.8Hz),138.01,137.24,131.51(d,J=10.2Hz),130.26(d,J=35.8Hz),128.79(d,J=4.8Hz),128.20,128.01,127.86(d,J=15.4Hz),126.24,118.13(d,J=222.3Hz),117.79,108.67(d,J=12.4Hz),63.28(d,J=5.6Hz),16.37(d,J=6.5Hz). 31 P NMR(162MHz,CDCl3)δ9.83.

[0076] Synthesis of diethyl [4-(4-nitrophenyl)pyrrolo[1,2-a]quinoxalin-1-yl]phosphate in Example 7

[0077] The specific synthesis steps of diethyl [4-(4-nitrophenyl)pyrrolo[1,2-a]quinoxalin-1-yl]phosphate in this example are as follows: Charge 1-iodo-4-(4-nitrophenyl)pyrrolo[1,2-a]quinoxaline (0.1 mmol, 0.0415 g) into a 10 mL three-necked quartz reaction tube. Under argon protection, add triethyl phosphite (1.0 mmol, 0.1662 g) and a solvent (1 mL). Stir the mixture for 6 h at room temperature under a light source with a wavelength of 390 nm. After the reaction is completed, remove the solvent under reduced pressure. Finally, purify the crude product by flash silica gel chromatography (petroleum ether / ethyl acetate = 2:1) to obtain 39.3 mg of the final product diethyl [4-(4-nitrophenyl)pyrrolo[1,2-a]quinoxalin-1-yl]phosphate, with a yield of 91%. The reaction formula is as follows:

[0078]

[0079] Diethyl [4-(4-nitrophenyl)pyrrolo[1,2-a]quinoxalin-1-yl]phosphate: 1 H NMR (400 MHz, CDCl3) δ 8.99 (dd, J = 8.8, 1.2 Hz, 1H), 8.41 (d, J = 8.8 Hz, 2H), 8.17 - 8.07 (m, 3H), 7.66 (ddd, J = 8.8, 7.2, 1.6 Hz, 1H), 7.62 - 7.54 (m, 2H), 6.97 (dd, J = 4.4, 3.0 Hz, 1H), 4.35 - 4.19 (m, 4H), 1.36 (t, J = 7.2 Hz, 6H). 13 C NMR (101 MHz, CDCl3) δ 151.94 (d, J = 1.8 Hz), 148.82, 143.96, 136.93, 130.81, 130.68, 129.94, 128.96, 128.30, 127.94 (d, J = 15.3 Hz), 126.60, 124.02, 120.22, 117.98, 108.17 (d, J = 12.5 Hz), 63.46 (d, J = 5.8 Hz), 16.41 (d, J = 6.4 Hz). 31 P NMR (162 MHz, CDCl3) δ 9.31.

[0080] Synthesis of diethyl [4-(4-nitrophenyl)pyrrolo[1,2-a]quinoxalin-1-yl]phosphate in Example 8

[0081] The specific synthesis steps of diethyl [4-(4-nitrophenyl)pyrrolo[1,2-a]quinoxalin-1-yl]phosphate in this example are as follows: Charge 1-iodo-4-(4-methoxyphenyl)pyrrolo[1,2-a]quinoxaline (0.1 mmol, 0.0385 g) into a 10 mL three-necked quartz reaction tube. Under argon protection, add triethyl phosphite (1.0 mmol, 0.1662 g) and a solvent (1 mL). Stir the mixture for 6 h at room temperature under a light source with a wavelength of 390 nm. After the reaction is completed, remove the solvent under reduced pressure. Finally, purify the crude product by flash silica gel chromatography (petroleum ether / ethyl acetate = 2:1) to obtain 38.2 mg of the final product diethyl [4-(4-methoxyphenyl)pyrrolo[1,2-a]quinoxalin-1-yl]phosphate, with a yield of 93%. The reaction formula is as follows:

[0082]

[0083] Diethyl [4-(4-methoxyphenyl)pyrrolo[1,2-a]quinoxalin-1-yl]phosphate: 1 H NMR (400 MHz, CDCl3) δ 8.93 (dd, J = 8.4, 1.4 Hz, 1H), 8.08 (dd, J = 7.8, 1.6 Hz, 1H), 7.92 (d, J = 8.8 Hz, 2H), 7.61 - 7.55 (m, 2H), 7.52 (ddd, J = 8.4, 7.2, 1.4 Hz, 1H), 7.07 (d, J = 2.0 Hz, 1H), 7.06 (d, J = 2.0 Hz, 1H), 7.03 (dd, J = 4.4, 3.0 Hz, 1H), 4.23 (dtdd, J = 10.0, 8.4, 7.6, 5.2 Hz, 4H), 3.89 (s, 3H), 1.34 (t, J = 7.2 Hz, 6H). 13 C NMR (101 MHz, CDCl3) δ 161.26, 153.96 (d, J = 1.8 Hz), 137.26, 131.55 (d, J = 10.2 Hz), 130.52, 130.35, 130.22, 128.03 (d, J = 10.0 Hz), 127.83, 127.71, 126.21, 118.01 (d, J = 222.6 Hz), 117.76, 114.19, 108.66 (d, J = 12.6 Hz), 63.28 (d, J = 5.6 Hz), 55.56, 16.37 (d, J = 6.5 Hz). 31 P NMR (162 MHz, CDCl3) δ 9.94.

[0084] Synthesis of diethyl (7-methylpyrrolo[1,2-a]quinoxalin-1-yl)phosphate in Example 9

[0085] In this example, the specific synthesis steps of diethyl (7-methylpyrrolo[1,2-a]quinoxalin-1-yl) phosphate are as follows: Place 1-iodo-7-methylpyrrolo[1,2-a]quinoxaline (0.1 mmol, 0.0308 g) into a 10 mL three-necked quartz reaction tube. Under argon protection, add triethyl phosphite (1.0 mmol, 0.1662 g) and a solvent (1 mL). Stir the mixture at room temperature under a light source with a wavelength of 390 nm for 6 h. After the reaction is complete, remove the solvent under reduced pressure. Finally, purify the crude product by flash column chromatography on silica gel (petroleum ether / ethyl acetate = 2:1) to obtain 22 mg of the final product diethyl (7-methylpyrrolo[1,2-a]quinoxalin-1-yl) phosphate, with a yield of 70%. The reaction formula is as follows:

[0086]

[0087] diethyl (7-methylpyrrolo[1,2-a]quinoxalin-1-yl) phosphate 1 H NMR (400 MHz, CDCl3) δ 8.87 (s, 1H), 8.79 (d, J = 8.8 Hz, 1H), 7.81 (s, 1H), 7.52 (dd, J = 4.4, 3.6 Hz, 1H), 7.42 (dd, J = 8.8, 2.0 Hz, 1H), 6.91 (dd, J = 4.4, 3.0 Hz, 1H), 4.20 (dtdd, J = 11.6, 10.0, 8.4, 7.2 Hz, 4H), 2.51 (s, 3H), 1.32 (t, J = 7.2 Hz, 6H). 13 C NMR (101 MHz, CDCl3) δ 145.48, 136.90, 136.14, 132.13 (d, J = 10.1 Hz), 130.01, 129.65, 127.52 (d, J = 15.9 Hz), 127.03, 117.70, 117.40 (d, J = 222.7 Hz), 107.15 (d, J = 12.7 Hz), 63.25 (d, J = 5.6 Hz), 21.03, 16.36 (d, J = 6.6 Hz). 31 P NMR (162 MHz, CDCl3) δ 9.79.

[0088] Synthesis of dimethyl pyrrolo[1,2-a]quinoxalin-1-yl phosphate in Example 10

[0089] The specific synthesis steps of dimethyl pyrrolo[1,2-a]quinoxalin-1-yl phosphate in this example are as follows: Charge 1-iodopyrrolo[1,2-a]quinoxaline (0.1 mmol, 0.0294 g) into a 10 mL three-necked quartz reaction tube. Under argon protection, add trimethyl phosphite (1.0 mmol, 0.1241 g) and a solvent (1 mL). Stir the mixture for 6 h at room temperature under a light source with a wavelength of 390 nm. After the reaction is completed, remove the solvent under reduced pressure. Finally, purify the crude product by silica gel flash chromatography (petroleum ether / ethyl acetate = 3:1) to obtain 22.2 mg of the final product dimethyl pyrrolo[1,2-a]quinoxalin-1-yl phosphate, with a yield of 81%. The reaction formula is as follows:

[0090]

[0091] Dimethyl pyrrolo[1,2-a]quinoxalin-1-yl phosphate: 1 H NMR (400 MHz, CDCl3) δ 8.90 (d, J = 2.2 Hz, 1H), 8.83 (dd, J = 8.6, 1.2 Hz, 1H), 8.02 (dd, J = 8.0, 1.6 Hz, 1H), 7.62 (ddd, J = 8.8, 7.2, 1.6 Hz, 1H), 7.57 - 7.49 (m, 2H), 6.94 (dd, J = 4.4, 3.0 Hz, 1H), 3.84 (d, J = 11.6 Hz, 6H). 13 C NMR (101 MHz, CDCl3) δ 145.55 (d, J = 1.6 Hz), 136.95, 132.36 (d, J = 10.3 Hz), 130.44, 129.08, 128.76, 127.96 (d, J = 15.7 Hz), 126.25, 117.58, 116.27 (d, J = 224.5 Hz), 107.39 (d, J = 12.7 Hz), 53.61 (d, J = 5.8 Hz). 31 P NMR (162 MHz, CDCl3) δ 12.83.

[0092] Synthesis of diisopropyl (pyrrolo[1,2-a]quinoxalin-1-yl)phosphine oxide in Example 11

[0093] The specific synthesis steps of diisopropyl (pyrrolo[1,2-a]quinoxalin-1-yl)phosphine oxide in this example are as follows: Charge 1-iodopyrrolo[1,2-a]quinoxaline (0.1 mmol, 0.0294 g) into a 10 mL three-necked quartz reaction tube. Under argon protection, add triisopropyl phosphite (1.0 mmol, 0.2082 g) and a solvent (1 mL). Stir the mixture under a light source with a wavelength of 390 nm at room temperature for 6 h. After the reaction is completed, remove the solvent under reduced pressure. Finally, purify the crude product by flash silica gel chromatography (petroleum ether / ethyl acetate = 3:1) to obtain 23.4 mg of the final product diisopropyl (pyrrolo[1,2-a]quinoxalin-1-yl)phosphine oxide, with a yield of 72%. The reaction formula is as follows:

[0094]

[0095] Diisopropyl (pyrrolo[1,2-a]quinoxalin-1-yl)phosphine oxide: 1 H NMR(400MHz,CDCl3)δ8.96(dd,J=8.4,1.2Hz,1H),8.89(d,J=2.2Hz,1H),8.01(dd,J=8.0,1.6Hz,1H),7.63-7.56(m,2H),7.51(ddd,J=8.4,7.2,1.4Hz,1H),6.93(dd,J=4.2,3.0Hz,1H),4.80(dp,J=8.0,6.4Hz,2H),1.37(d,J=6.0Hz,6H),1.24(d,J=6.4Hz,6H). 13 C NMR(101

[0096] MHz,CDCl3)δ145.64,136.88,132.05(d,J=10.1Hz),130.18,129.15,128.12,12

[0097] 7.90(d,J=15.9Hz),126.11,119.48(d,J=222.0Hz),118.52,107.36(d,J=12.7Hz),72.40(d,J=5.7Hz),24.17(d,J=4.1Hz),23.84(d,J=5.0Hz). 31 P NMR(162MHz,CDCl3)δ7.06.

[0098] Synthesis of dibutyl (pyrrolo[1,2-a]quinoxalin-1-yl) phosphate in Example 12

[0099] The specific synthesis steps of dibutyl (pyrrolo[1,2-a]quinoxalin-1-yl) phosphate in this example are as follows: Charge 1-iodopyrrolo[1,2-a]quinoxaline (0.1 mmol, 0.0294 g) into a 10 mL three-necked quartz reaction tube. Under argon protection, add tributyl phosphite (1.0 mmol, 0.2503 g) and a solvent (1 mL). Stir the mixture at room temperature under a light source with a wavelength of 390 nm for 6 h. After the reaction is completed, remove the solvent under reduced pressure. Finally, purify the crude product by flash silica gel chromatography (petroleum ether / ethyl acetate = 3:1) to obtain 28.4 mg of the final product dibutyl (pyrrolo[1,2-a]quinoxalin-1-yl) phosphate, with a yield of 81%. The reaction formula is as follows:

[0100]

[0101] Dibutyl (pyrrolo[1,2-a]quinoxalin-1-yl) phosphate: 1 H NMR(400MHz,CDCl3)δ8.94-8.87(m,2H),8.02(dd,J=8.0,1.6Hz,1H),7.59(ddd,J=8.8,7.2,1.6Hz,1H),7.56-7.49(m,2H),6.94(dd,J=4.2,3.0Hz,1H),4.13(dddd,J=16.8,14.0,8.4,4.8Hz,4H),1.69-1.59(m,4H),1.36(h,J=7.2Hz,4H),0.85(t,J=7.6Hz,6H). 13 C NMR(101MHz,CDCl3)δ145.58,136.89,132.15(d,J=10.2Hz),130.28,129.10,128.42,127.77(d,J=15.8Hz),126.17,117.99,117.83(d,J=222.6Hz),107.35(d,J=12.8Hz),66.94(d,J=5.9Hz),32.40(d,J=6.6Hz),18.83,13.58. 31 P NMR(162MHz,CDCl3)δ9.90.

[0102] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit them. Although the present invention has been described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand that the technical solutions of the present invention can be modified or equivalently replaced without departing from the spirit and scope of the technical solutions of the present invention, and they should all be covered by the scope of the claims of the present invention.

Claims

1. A method for constructing a C-P bond based on halogenated pyrrolo[1,2-a]quinoxaline, characterized in that, The method comprises the following steps: Under visible light irradiation, a halogenated pyrrolo[1,2-a]quinoxaline and a phosphite are mixed in a solvent and stirred at room temperature for reaction to obtain a phosphonate ester of a nitrogen-containing fused heterocyclic aromatic hydrocarbon and its derivatives.

2. The method according to claim 1, wherein The general reaction formula is as follows: Among them, R 1 is a substituent at the 7- or 8-position on the benzene ring; R 2 is 4-phenyl, 4-NO2 phenyl or 4-OMe group; R 3 is Me, i Pr or n Bu.

3. The method according to claim 2, characterized in that, The R 1 is selected from H, Me or Cl.

4. The method according to claim 1, characterized in that The wavelength of the visible light is 390 nm, and the solvent is selected from dichloromethane or acetonitrile.

5. The method according to claim 1, characterized in that The molar ratio of the halogenated pyrrolo[1,2-a]quinoxaline to the phosphite is 1:

10.

6. The method according to claim 1, characterized in that, The reaction time is 3 - 12 hours, and the reaction is carried out in an inert gas atmosphere.

7. The method according to claim 1, characterized in that The method further comprises the step of purifying the obtained phosphonate ester of a nitrogen-containing fused heterocyclic aromatic hydrocarbon and its derivatives.

8. A phosphonate ester of a nitrogen-containing fused heterocyclic aromatic hydrocarbon and its derivatives prepared by using the method according to any one of claims 1 - 7.

9. The phosphonate ester and its derivatives of the nitrogen-containing fused heterocyclic aromatic hydrocarbon according to claim 8, characterized in that, The phosphonate esters of the nitrogen-containing fused heterocyclic aromatic hydrocarbons include 1-(pyrrolo[1,2-a]quinoxalin-1-yl)diethyl phosphonate and 3-(pyrrolo[1,2-a]quinoxalin-3-yl)diethyl phosphonate.

10. Use of the phosphonate esters of the nitrogen-containing fused heterocyclic aromatic hydrocarbons and their derivatives according to any one of claims 8 - 9 in the fields of drug synthesis, materials science or catalysis.

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