Quinoxaline compound direct diphosphorylation reaction method and application
By using quinoxaline compounds with diaryloxyphosphorus and other compounds in an oxygen-free environment, the problems of limited substrate range and harsh reaction conditions in the prior art are solved, and the efficient bisphosphoration of quinoxaline compounds is achieved, with the advantages of mild conditions, low by-products and high yields.
Patent Information
- Application Number
- CN202510005211.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-01-02
- Publication Date
- 2025-04-11
AI Technical Summary
The existing bisphosphonation reaction methods have limited substrate range and harsh reaction conditions, requiring catalysts, strong oxidants, photocatalysis or electrocatalysis, and no direct bisphosphonation reaction of quinoxaline is reported.
Quinoxaline compounds are used as substrates and diaryloxyphosphoric acid, phosphate or phosphite esters are used as phosphorus sources to directly synthesize bisphosphonated quinoxaline compounds in an oxygen-free environment. Through the combination of magnetons and solvents, a catalyst-free nucleophilic bisphosphonation reaction is achieved.
Bisphosphonation of quinoxaline compounds was achieved under mild conditions, with mild reaction conditions, few by-products, easy to separate and purify, environmentally friendly, easy to operate, wide application range, good yield (up to 98%).
Smart Images
Figure CN119798324A_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of green organic synthesis, and specifically relates to a direct bisphosphonylation reaction method and application of a quinoxaline compound, which is mainly used for synthesizing bisphosphonylated quinoxaline compounds and derivatizing bisphosphine partners. Background Art
[0002] Organophosphine compounds have attracted much attention from chemical researchers due to their wide applications in natural products, organic synthesis, medicine, materials science, and transition metal ligands. In organic synthesis, organophosphorus compounds are not only common intermediates, but also very useful ligand compounds in transition metal complexes. One of the important ligands, the bisphosphine ligand, contains a bisphosphonylated skeleton structure. Therefore, developing efficient bisphosphonylation reactions and achieving precise construction of bisphosphine ligands have gradually become research hotspots.
[0003] In recent years, relevant research has made significant breakthroughs, especially in the bisphosphonylation of alkenes, alkynes and quinoline. Commonly used bisphosphonylation methods include Figure 1 As shown. Among them, Figure 1 a) in the figure is that the Ogawa group used free radical initiators or near-ultraviolet light to induce the generation of phosphine radicals to achieve a highly selective bisphosphonylation reaction of olefins, and tetraphenyldiphosphine oxide was regioselectively added to olefins to obtain 1,2-diphenylphosphine oxide, which was further treated with S8 to obtain a practical bisphosphine ligand. Figure 1 b) to e) in the reaction are to use simple and readily available alkynes as substrates to directly synthesize alkyl diphosphonylation products through double addition reactions, which is one of the most atom-economical methods for obtaining such compounds. Figure 1 f) in the figure shows that Stevens' group used a one-pot cascade approach under strong acid conditions to use trialkyl and silylated dimethyl phosphites as nucleophiles to undergo 1,4- and 1,2-addition reactions with quinoline to achieve selective bisphosphonylation of quinoline. Figure 1 g) is a double addition reaction of diarylphosphine oxide and quinoline achieved by Trofimov et al. under mild conditions without a catalyst to obtain 2,4-diphosphotetrahydroisoquinoline in excellent yield. Figure 1 h) in the figure is that Cai et al. used iodine as an oxidant to achieve a metal-free selective diphosphination reaction of benzoxazole with trialkylphosphites under mild conditions, and a series of phosphites showed high reactivity.
[0004] Although the bisphosphonylation reaction has made some progress in recent years, there is still room for improvement in the scope of substrates and reaction conditions, especially the direct bisphosphonylation reaction of quinoxaline has not been reported in the literature. In view of the above problems, it is of great scientific value to study and develop a method to synthesize bisphosphonylated quinoxaline compounds with simple and readily available raw materials through efficient and environmentally friendly methods. Summary of the invention
[0005] 1. Technical issues to be resolved
[0006] The present invention provides a direct bisphosphonylation reaction method and application of quinoxaline compounds, so as to solve the technical problems that the substrate range of previous bisphosphonylation reaction research is limited and the reaction conditions are relatively harsh, requiring catalysts, strong oxidants, photocatalysis, electrocatalysis and other reaction conditions.
[0007] (II) Technical solution
[0008] In order to solve the above technical problems, the present invention provides a direct bisphosphonylation reaction method for quinoxaline compounds, which comprises taking a quinoxaline compound as a substrate and a diarylphosphine oxide, a phosphate or a phosphite as a phosphorus source to directly synthesize a bisphosphonylated quinoxaline compound in an oxygen-free environment.
[0009] Furthermore, the direct bisphosphonylation reaction method of quinoxaline compounds specifically comprises the following steps:
[0010] S1. Adding a diarylphosphine oxide, a phosphate or a phosphite to a reaction tube, placing a magnet in the reaction tube, and adding a solvent to the reaction tube to form an oxygen-free environment in the reaction tube; placing the reaction tube on a thermostatic stirrer;
[0011] S2. Injecting quinoxaline into the reaction tube, performing a synthesis reaction at a constant temperature to obtain a reaction solution;
[0012] S3. Purify the reaction solution to obtain pure bisphosphonylated quinoxaline compounds.
[0013] Furthermore, in step S1, the method for forming an anaerobic environment is to insert two needles into the rubber stopper of the reaction tube, introduce an inert gas into the reaction tube through one needle, and exhaust the air in the reaction tube through another needle; or directly inject a solvent into the reaction tube so that the solvent fills the reaction tube.
[0014] Furthermore, in step S3, when the reaction solution is purified, the reaction solution is evenly spread on the surface of a silica gel column and separated by column chromatography to obtain a pure bisphosphonylated quinoxaline compound.
[0015] Furthermore, in step S3, when the reaction solution is purified, the poorly soluble bisphosphonylated quinoxaline compounds are purified by filtration or recrystallization to obtain pure bisphosphonylated quinoxaline compounds.
[0016] Furthermore, the solvent is n-hexane, acetonitrile, dimethyl sulfoxide or an ether solvent.
[0017] In addition, the present invention also proposes an application of the above-mentioned direct bisphosphonylation reaction method of quinoxaline compounds, wherein the synthesized bisphosphonyl quinoxaline compounds are subjected to a derivatization reaction to obtain an aromatization product, a monothioated product or a dithioated product.
[0018] Further, the synthesized bisphosphonylated quinoxaline compound is subjected to a derivatization reaction to obtain an aromatization product, comprising the following steps:
[0019] S1. Add the synthesized bisphosphonylated quinoxaline compound to a reaction tube, place a magnet in the reaction tube, add a solvent to the reaction tube, and place the reaction tube on a constant temperature stirrer;
[0020] S2. adding an oxidant to the reaction tube to carry out an aromatization reaction of the bisphosphonylated quinoxaline compound to obtain an aromatization reaction liquid;
[0021] S3. Purifying the aromatization reaction liquid to obtain a pure aromatization product.
[0022] Furthermore, the synthesized aromatized bisphosphonylated quinoxaline compound is subjected to a derivatization reaction to obtain a monothio product, which specifically includes the following steps:
[0023] S1. Add the synthesized aromatized bisphosphonylated quinoxaline compound to a reaction tube, place a magnet in the reaction tube, add a solvent to the reaction tube, and place the reaction tube on a constant temperature stirrer;
[0024] S2. Add a sulfiding agent to the reaction tube, and carry out a monosulfidation reaction of the bisphosphonylated quinoxaline compound at room temperature to 45° C. to obtain a monosulfidation reaction solution;
[0025] S3. Purify the monosulfide reaction solution to obtain a pure monosulfide product.
[0026] Furthermore, the synthesized aromatized bisphosphonylated quinoxaline compound is subjected to a derivatization reaction to obtain a dithio product, which specifically includes the following steps:
[0027] S1. Add the synthesized aromatized bisphosphonylated quinoxaline compound to a reaction tube, place a magnet in the reaction tube, add a solvent to the reaction tube, and place the reaction tube on a constant temperature stirrer;
[0028] S2. Add a sulfiding agent to the reaction tube, heat to above 45° C., and perform a disulfidation reaction of the bisphosphonylated quinoxaline compound to obtain a disulfidation reaction solution;
[0029] S3. Purify the dithiolation reaction solution to obtain a pure dithiolation product.
[0030] (III) Beneficial effects
[0031] The present invention provides a direct bisphosphonylation reaction method and application of quinoxaline compounds, using quinoxaline compounds as raw materials, diarylphosphine oxides, phosphates or phosphites as phosphorus sources, adding readily available solvents, and directly synthesizing bisphosphonylated quinoxaline compounds in an oxygen-free environment without a catalyst. The present invention can realize the nucleophilic bisphosphonylation reaction of quinoxaline compounds under mild conditions without a catalyst, and can be used to synthesize a series of bisphosphonylated quinoxaline compounds. The reaction method has the advantages of mild reaction conditions, few by-products and easy separation and purification, environmental friendliness, simple operation, wide application range, good yield (up to 98%), etc., and gram-scale reactions and derivatization reactions show the potential application value of the reaction method.
[0032] Compared with the prior art, the beneficial effects of the present invention specifically include:
[0033] 1. The present invention has set a precedent for the diphosphonylation reaction of quinoxaline and is original. Compared with the diphosphonylation reaction methods of other substances, this method still has significant advantages. In terms of reaction mechanism, this reaction verifies its reaction mechanism of nucleophilic addition. In the past, most reactions used free radical initiation methods, which often required harsh reaction conditions such as catalysts, strong oxidants, photocatalysis, and electrocatalysis. This method overcomes the above shortcomings and is more in line with the reaction trend of green chemistry. It can achieve a maximum yield of 98% without the need for catalysts or oxidants to obtain diphosphonyl quinoxaline compounds.
[0034] 2. The reaction uses only readily available reaction solvents such as ether or isopropyl ether, without adding any other auxiliary substances. In an oxygen-free environment, no by-products generated by other quinoxaline compounds are generated, and it is easy to achieve complete reaction with a higher yield. Only the excess reaction reagent needs to be separated and removed, which is convenient to operate and easy to purify. The raw materials react in a solid-liquid manner, the reaction process is easy to control, and the safety risk is low.
[0035] 3. The reaction is suitable for synthesis on a gram scale or above. At the same time, the derivatization reaction method realizes the aromatization, monothiolation, and dithiolation of quinoxaline-based bisphosphonylation products, and can synthesize the corresponding bisphosphine ligands, which has a wide range of application potentials. BRIEF DESCRIPTION OF THE DRAWINGS
[0036] Figure 1 It is a commonly used bisphosphonylation reaction method;
[0037] Figure 2 The product of Example 1 (tetrahydroquinoxaline-2,3-diyl)bis(diphenylphosphine oxide) 1 H-NMR spectrum;
[0038] Figure 3The product of Example 1 (tetrahydroquinoxaline-2,3-diyl)bis(diphenylphosphine oxide) 31 P-NMR spectrum;
[0039] Figure 4 The aromatization product of Example 1 (quinoxaline-2,3-diyl)bis(diphenylphosphine oxide) 1 H-NMR spectrum;
[0040] Figure 5 The aromatization product of Example 1 (quinoxaline-2,3-diyl)bis(diphenylphosphine oxide) 31 P-NMR spectrum;
[0041] Figure 6 The dithio product (quinoxaline-2,3-diyl)bis(diphenylphosphine sulfide) of Example 1 1 H-NMR spectrum;
[0042] Figure 7 The dithio product (quinoxaline-2,3-diyl)bis(diphenylphosphine sulfide) of Example 1 31 P-NMR spectrum;
[0043] Figure 8 The product of Example 2 (tetrahydroquinoxaline-2,3-diyl)bis(di(4-trifluoromethyl)phenyl)phosphine oxide 1 H-NMR spectrum;
[0044] Fig. 9 The product of Example 2 (tetrahydroquinoxaline-2,3-diyl)bis(di(4-trifluoromethyl)phenyl)phosphine oxide 31 P-NMR spectrum;
[0045] Fig.10 The product of Example 3 (5-methyl-tetrahydroquinoxaline-2,3-diyl)bis(diphenylphosphine oxide) 1 H-NMR spectrum;
[0046] Fig.11 The product of Example 3 (5-methyl-tetrahydroquinoxaline-2,3-diyl)bis(diphenylphosphine oxide) 31 P-NMR spectrum. DETAILED DESCRIPTION
[0047] In order to make the purpose, content and advantages of the present invention more clear, the specific implementation methods of the present invention are further described in detail below in conjunction with the drawings and examples.
[0048] Example 1
[0049] This embodiment provides a method for synthesizing (tetrahydroquinoxaline-2,3-diyl)bis(diphenylphosphine oxide), comprising the following steps:
[0050] S1. Add diphenylphosphine oxide (161.8 mg, 4.0 equiv) into a 10 mL reaction tube, place a magnetic bar into the reaction tube, and add ether solvent (2 mL) into the reaction tube.
[0051] S2. Remove the air in the bottle by ultrasonic treatment until no bubbles float up, tighten the rubber stopper, place the reaction bottle on a constant temperature stirrer (rad = 600 rpm), insert two needles into the rubber stopper of the reaction tube, pass nitrogen through one needle, and exhaust the air in the reaction tube through the other needle. Replace it three times to exhaust the air in the reaction tube.
[0052] S3. Inject quinoxaline (26.0 mg, 1.0 equiv) into the reaction tube using a syringe, and react at a constant temperature of 35° C. for about 24 hours to obtain a reaction solution.
[0053] S4. The reaction solution was evenly spread on the surface of a silica gel column, and separated and purified by column chromatography using petroleum ether / ethyl acetate (1:1) as the eluent, and then further purified by the same operation using dichloromethane / methanol (20:1) as the eluent to obtain a pure bisphosphonylated quinoxaline compound.
[0054] The yield of (tetrahydroquinoxaline-2,3-diyl)bis(diphenylphosphine oxide) obtained by the above method was 91% and the purity was 99%.
[0055] The characterization data of the obtained product are: 1 H NMR(600MHz,CD3OD)δ7.90(dt,J=10.6,4.2Hz,2H),7.67–7.59(m,3H),7.55(t,J=7.4Hz,2H),7.32(t,J=7.2H z,1H),7.19(t,J=7.5Hz,2H),6.20(dd,J=5.9,3.3Hz,1H),6.02(dd,J=5.8,3.4Hz,1H),5.07(d,J=2.5Hz,1H); 31 P NMR (243MHz, CDCl3): δ (ppm) 31.28.
[0056] The derivatization reaction using (tetrahydroquinoxaline-2,3-diyl)bis(diphenylphosphine oxide) as a substrate to obtain an aromatization product comprises the following steps:
[0057] S1. Add the synthesized (tetrahydroquinoxaline-2,3-diyl)bis(diphenylphosphine oxide) (1070 mg, 2 mmol, 1.0 equiv) into a 10 mL reaction tube, place a magnetic bar in the reaction tube, add tetrahydrofuran solvent (100 mL) into the reaction tube, and place the reaction tube on a constant temperature stirrer (rad = 700 rpm).
[0058] S2. Add oxidant DDQ (908 mg, 4 mmol, 2.0 equiv) into the reaction tube and react for about 4 hours at room temperature to obtain an aromatization reaction solution.
[0059] S3. The reaction solution was evenly spread on the surface of a silica gel column, and petroleum ether / ethyl acetate (1:1) was used as an eluent to separate and purify by column chromatography to obtain a pure aromatization product.
[0060] The aromatization product 2,3-bis(diphenylphosphine)quinoxaline obtained by the above method has a yield of 79% and a purity of 99%.
[0061] The characterization data of the obtained product are: 1 H NMR (600MHz, CD3OD) δ7.95–7.84(m,4H),7.64–7.53(m,8H),7.47(td,J=7.5,1.4Hz,5H),7.35(td,J=7.8,2.7Hz,8H); 31 PNMR (243MHz, CD3OD)δ29.00.
[0062] The steps of the derivatization reaction using (quinoxaline-2,3-diyl)bis(diphenylphosphine oxide) as a substrate to obtain the dithiothionate are as follows:
[0063] S1. Add the synthesized (quinoxaline-2,3-diyl)bis(diphenylphosphine oxide) (53.2 mg, 0.1 mmol, 1.0 equiv) into a 10 mL reaction tube, place a magnetic bar in the reaction tube, add xylene solvent (5 mL) into the reaction tube, and place the reaction tube on a constant temperature stirrer (rad = 600 rpm).
[0064] S2. Add Lawesson's reagent (80.8 mg, 0.2 mmol, 2 equiv) into the reaction tube, heat to 60° C., and react at constant temperature for about 12 hours to obtain a dithiolation reaction solution.
[0065] S3. The dithiothion reaction solution was evenly spread on the surface of a silica gel column, and petroleum ether / ethyl acetate (10:1) was used as an eluent to separate and purify the product by column chromatography to obtain a pure dithiothion product.
[0066] The dithio product (quinoxaline-2,3-diyl)bis(diphenylphosphine sulfide) obtained by the above method has a yield of 88% and a purity of 99%.
[0067] The characterization data of the obtained product are: 1 HNMR (600MHz, CDCl3) δ7.77 (q, J=6.9Hz, 12H), 7.48 (td, J=7.3, 1.5Hz, 4H), 7.43–7.37 (m, 8H); 31 PNMR (243MHz, CDCl3): δ (ppm) 46.39.
[0068] Example 2
[0069] This embodiment provides a method for synthesizing (tetrahydroquinoxaline-2,3-diyl)bis(di(4-trifluoromethyl)phenyl)phosphine oxide, comprising the following steps:
[0070] S1. Add bis(4-(trifluoromethyl)phenyl)phosphine oxide (270 mg, 4.0 equiv) into a 10 mL reaction tube, place a magnetic bar into the reaction tube, and add ether solvent (4 mL) into the reaction tube.
[0071] S2. Remove the air in the bottle by ultrasonic treatment until no bubbles float up, tighten the rubber stopper, place the reaction bottle on a constant temperature stirrer (rad = 600 rpm), insert two needles into the rubber stopper of the reaction tube, pass nitrogen through one needle, and exhaust the air in the reaction tube through the other needle. Replace it three times to exhaust the air in the reaction tube.
[0072] S3. Inject quinoxaline (26.0 mg, 1.0 equiv) into the reaction tube using a syringe, and react at a constant temperature of 35° C. for about 24 hours to obtain a reaction solution.
[0073] S4. The reaction solution was evenly spread on the surface of a silica gel column, and separated and purified by column chromatography using petroleum ether / ethyl acetate (1:1) as the eluent. Then, the same operation was used to further purify using dichloromethane / methanol (20:1) as the eluent to obtain a pure bisphosphonylated product.
[0074] The yield of (tetrahydroquinoxaline-2,3-diyl)bis(bis(4-trifluoromethyl)phenyl)phosphine oxide obtained by the above method was 76% and the purity was 99%.
[0075] The characterization data of the obtained product are: 1H NMR (600MHz, CD3OD) δ8.22(dd,J=9.7,8.4Hz,4H),7.92(d,J=7.7Hz,4H),7.78(dd,J=10.3,8.2 Hz,4H),7.40(d,J=7.8Hz,4H),6.21–6.11(m,2H),5.96–5.86(m,2H),5.28(s,2H),4.59(s,2H); 31 P NMR (243MHz, CD3OD)δ27.69.
[0076] Example 3
[0077] This embodiment provides a method for synthesizing (5-methyl-tetrahydroquinoxaline-2,3-diyl)bis(diphenylphosphine oxide), comprising the following steps:
[0078] S1. Add diphenylphosphine oxide (161.8 mg, 4.0 equiv) to a 10 mL reaction tube, place a magnetic bar in the reaction tube, and add ether solvent (2 mL) to the reaction tube;
[0079] S2. Remove the air in the bottle by ultrasonic treatment until no bubbles float up, tighten the rubber stopper, place the reaction bottle on a constant temperature stirrer (rad = 600 rpm), insert two needles into the rubber stopper of the reaction tube, pass nitrogen through one needle, and exhaust the air in the reaction tube through the other needle, replace it three times, and exhaust the air in the reaction tube;
[0080] S3. 5-methylquinoxaline (28.8 mg, 1.0 equiv) was injected into the reaction tube by syringe, and the reaction was carried out at a constant temperature of 35° C. for about 24 hours to obtain a reaction solution;
[0081] S4. The reaction solution was evenly spread on the surface of a silica gel column, and separated and purified by column chromatography using petroleum ether / ethyl acetate (1:1) as the eluent. Then, the same operation was used to further purify using dichloromethane / methanol (20:1) as the eluent to obtain a pure bisphosphonylated product.
[0082] The yield of (5-methyl-tetrahydroquinoxaline-2,3-diyl)bis(diphenylphosphine oxide) obtained by the above method was 88% and the purity was 99%.
[0083] The characterization data of the obtained product are: 1H NMR (600MHz, CD3OD) δ7.99 (dd, J=13.9, 4.9Hz, 2H), 7.92 (dd, J=9.2, 8.4Hz, 2 H),7.66–7.59(m,4H),7.56(dt,J=14.4,5.4Hz,6H),7.28(dtd,J=8.4,7.6,1. 0Hz,2H),7.20–7.09(m,4H),6.15(t,J=7.6Hz,1H),6.06(d,J=7.2Hz,1H),5.9 5(d,J=7.7Hz,1H),5.13(t,J=4.5Hz,1H),5.09(d,J=2.4Hz,1H),1.64(s,3H); 31 PNMR(243MHz,CD3OD)δ31.19,31.14.
[0084] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the technical principles of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.
Claims
1. A method for direct bisphosphonylation of quinoxaline compounds, characterized in that: The direct bisphosphonylation reaction method of quinoxaline compounds comprises the following steps: using quinoxaline compounds as substrates and diarylphosphine oxides, phosphates or phosphites as phosphorus sources to directly synthesize bisphosphonylated quinoxaline compounds in an oxygen-free environment.
2. The direct bisphosphonylation reaction method of quinoxaline compounds according to claim 1, characterized in that: The direct bisphosphonylation reaction method of quinoxaline compounds specifically comprises the following steps: S1. Adding a diarylphosphine oxide, a phosphate or a phosphite to a reaction tube, placing a magnet in the reaction tube, and adding a solvent to the reaction tube to form an oxygen-free environment in the reaction tube, and placing the reaction tube on a constant temperature stirrer; S2. Injecting quinoxaline into the reaction tube, performing a synthesis reaction at a constant temperature to obtain a reaction solution; S3. Purify the reaction solution to obtain pure bisphosphonylated quinoxaline compounds.
3. The direct bisphosphonylation reaction method of quinoxaline compounds according to claim 2, characterized in that: In step S1, the method for forming an oxygen-free environment is to insert two needles into the rubber stopper of the reaction tube, introduce an inert gas into the reaction tube through one needle, and exhaust the air in the reaction tube through the other needle; or directly inject a solvent into the reaction tube so that the solvent fills the reaction tube.
4. The direct bisphosphonylation reaction method of quinoxaline compounds according to claim 2, characterized in that: In step S3, when purifying the reaction solution, the reaction solution is evenly spread on the surface of a silica gel column and separated by column chromatography to obtain a pure bisphosphonylated quinoxaline compound.
5. The direct bisphosphonylation reaction method of quinoxaline compounds according to claim 4, characterized in that: In step S3, when the reaction solution is purified, the poorly soluble bisphosphonylated quinoxaline compounds are purified by filtration or recrystallization to obtain pure bisphosphonylated quinoxaline compounds.
6. The direct bisphosphonylation reaction method of quinoxaline compounds according to claim 2, characterized in that: The solvent is n-hexane, acetonitrile, dimethyl sulfoxide or an ether solvent.
7. An application of the method for direct bisphosphonylation of quinoxaline compounds as claimed in any one of claims 1 to 6, characterized in that: The synthesized bisphosphonylated quinoxaline compounds are subjected to a derivatization reaction to obtain an aromatized product, a monothioated product or a dithioated product.
8. The use of the direct bisphosphonylation reaction method of quinoxaline compounds as claimed in claim 7, characterized in that: The synthesized bisphosphonylated quinoxaline compound is subjected to a derivatization reaction to obtain an aromatization product, comprising the following steps: S1. Add the synthesized bisphosphonylated quinoxaline compound to a reaction tube, place a magnet in the reaction tube, add a solvent to the reaction tube, and place the reaction tube on a constant temperature stirrer; S2. adding an oxidant to the reaction tube to carry out an aromatization reaction of the bisphosphonylated quinoxaline compound to obtain an aromatization reaction liquid; S3. Purifying the aromatization reaction liquid to obtain a pure aromatization product.
9. The use of the direct bisphosphonylation reaction method of quinoxaline compounds as claimed in claim 7, characterized in that: The synthesized aromatized bisphosphonylated quinoxaline compound is subjected to a derivatization reaction to obtain a monothio product, which specifically comprises the following steps: S1. Add the synthesized aromatized bisphosphonylated quinoxaline compound to a reaction tube, place a magnet in the reaction tube, add a solvent to the reaction tube, and place the reaction tube on a constant temperature stirrer; S2. Add a sulfiding agent to the reaction tube, and carry out a monosulfidation reaction of the bisphosphonylated quinoxaline compound at room temperature to 45° C. to obtain a monosulfidation reaction solution; S3. Purify the monosulfide reaction solution to obtain a pure monosulfide product.
10. The use of the direct bisphosphonylation reaction method of quinoxaline compounds as claimed in claim 7, characterized in that: The synthesized aromatized bisphosphonylated quinoxaline compound is subjected to a derivatization reaction to obtain a dithio product, which specifically comprises the following steps: S1. Add the synthesized bisphosphonylated quinoxaline compound to a reaction tube, place a magnet in the reaction tube, add a solvent to the reaction tube, and place the reaction tube on a constant temperature stirrer; S2. Add a sulfiding agent to the reaction tube, heat to above 45° C., and perform a disulfidation reaction of the bisphosphonylated quinoxaline compound to obtain a disulfidation reaction solution; S3. Purify the dithiolation reaction solution to obtain a pure dithiolation product.