Process for the preparation of (2-(3,6-dimethoxy-9H-carbazol-9-yl)ethyl)phosphonic acid

Abstract

The application provides a process method for preparing (2-(3,6-dimethoxy-9H-carbazol-9-yl)ethyl) phosphonic acid, and particularly relates to the technical field of organic synthesis. The process method is that, under alkaline conditions, a halogenated phosphonate compound is added into a 3,6-dimethoxy-9H-carbazole solution to perform a reaction, hydrochloric acid aqueous solution is added after the reaction to perform acidolysis degreasing, and finally (2-(3,6-dimethoxy-9H-carbazol-9-yl)ethyl) phosphonic acid is obtained through extraction, reflux adsorption and beating purification. The process method uses 3,6-dimethoxy-9H-carbazole as a starting material, realizes the synthesis of the target product through one-pot reaction, has mild reaction conditions, uses non-toxic raw materials which are easy to obtain, has simple synthesis process, is convenient to operate, and has high separation yield.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and in particular to a process for preparing (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid. Background Technology

[0002] Perovskite solar cells are a novel type of solar cell, composed of multiple thin films with perovskite crystals as the main material. Due to their large carrier diffusion length and suitable bandgap, perovskite solar cells have rapidly become a hot topic in photovoltaic research, possessing two key advantages: low economic cost and high optimal conversion efficiency. In recent years, self-assembled monolayers (SAM materials) have attracted considerable attention as an ideal hole transport layer material.

[0003] (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid is a type of carbazole-derived SAM material containing a phosphate group, which plays an important role in the uniform formation and performance improvement of perovskite films. Currently, the direct preparation method of this monomer mainly uses carbazole and its derivatives with disubstituted haloalkanes as starting materials. After alkylation, extraction, drying, concentration, and recrystallization, it reacts with triethyl phosphite, and finally undergoes deesterification and acid adjustment under alkaline conditions to obtain the target product. However, this synthetic route has the following drawbacks: expensive raw materials, complex and lengthy operation steps, incomplete alkaline hydrolysis of ethyl phosphite, and harsh reaction conditions, resulting in excessively high costs and difficulties in equipment selection, which is not conducive to large-scale mass production.

[0004] In view of this, the present invention is hereby proposed. Summary of the Invention

[0005] One of the objectives of this invention is to provide a process for preparing (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid, so as to alleviate at least one of the above-mentioned technical problems.

[0006] A second objective of this invention is to provide a (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid.

[0007] In order to achieve the above-mentioned objectives of the present invention, the following technical solution is adopted:

[0008] The first aspect of this invention provides a process for preparing (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid. Under alkaline conditions, a halophosphonate compound is added to a 3,6-dimethoxy-9H-carbazole solution for reaction. After the reaction is completed, hydrochloric acid aqueous solution is added for acid degreasing. Finally, extraction, reflux adsorption, and pulping purification are performed to obtain (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid.

[0009] Furthermore, the solvent used in the 3,6-dimethoxy-9H-carbazole solution includes dimethylformamide.

[0010] Preferably, the halophosphonate compound includes at least one of diethyl 2-bromoethylphosphonate, monoethyl bromoethylphosphonate, diethyl chloroethylphosphonate, and monoethyl chloroethylphosphonate.

[0011] Furthermore, the molar ratio of 3,6-dimethoxy-9H-carbazole to halophosphonate compounds is 1:1 to 3, preferably 1:1.5 to 2.8.

[0012] Preferably, a solid alkali is added to create alkaline conditions.

[0013] Preferably, the solid alkali includes at least one of potassium hydroxide, potassium tert-butoxide, and sodium hydroxide, with potassium hydroxide being the most preferred.

[0014] Preferably, the amount of the solid alkali added is 1.5 to 3.5 times the molar amount of 3,6-dimethoxy-9H-carbazole, and more preferably 1.8 to 3 times.

[0015] Furthermore, the reaction temperature is -10 to 60°C, preferably 0 to 30°C.

[0016] Preferably, the reaction time is 3 to 10 hours, and more preferably 4 to 8 hours.

[0017] Furthermore, the acid degreasing process is as follows: under liquid chromatography monitoring, the reaction system is heated and refluxed in an aqueous hydrochloric acid solution for hydrolysis.

[0018] Preferably, the concentration of the hydrochloric acid aqueous solution is 3-6 M.

[0019] Preferably, the heating and reflux time is 1 to 4 hours, more preferably 2 to 3 hours.

[0020] Furthermore, the extractant used in the extraction includes chloroform.

[0021] Preferably, the feed liquid is extracted in batches using an extractant, and then the organic phase is collected.

[0022] Preferably, the amount of the extractant is 0.5 to 3 times the weight of the raw material liquid.

[0023] Preferably, the extraction is performed 2 to 4 times.

[0024] Furthermore, the adsorbent used in the reflux adsorption includes activated carbon.

[0025] Preferably, an adsorbent is added to the organic phase for reflux adsorption, and then the filtrate is collected by filtration to obtain a pure organic phase.

[0026] Preferably, the amount of adsorbent added is 0.015 to 0.03 times the weight of the organic phase.

[0027] Furthermore, the pulping and purification process is as follows: a pulping solvent is added to the pure organic phase for pulping, and then cooled to precipitate (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid.

[0028] Furthermore, the pulping solvent includes petroleum ether.

[0029] Preferably, the mass of the pulping solvent is 3 to 5 times the mass of the pure organic phase.

[0030] Preferably, the cooling temperature is -5 to 20°C, and more preferably 0 to 5°C.

[0031] A second aspect of the present invention provides a (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid, which is prepared by the process described above.

[0032] Compared with the prior art, the present invention has at least the following beneficial effects:

[0033] The process provided by this invention uses 3,6-dimethoxy-9H-carbazole as the starting material and achieves the synthesis of the target product through a one-pot reaction. The reaction conditions are mild, the raw materials used are non-toxic and readily available, the synthesis process is simple, convenient to operate, and the separation yield is high. The use of hydrochloric acid aqueous solution for acid deesterification not only avoids the cumbersome post-treatment process of traditional liquid alkaline hydrolysis but also solves the problem of incomplete hydrolysis of diethyl phosphate under alkaline conditions, thereby significantly improving the purity of the synthesized product and making it more suitable for scale-up production.

[0034] The (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid provided by this invention, due to the advantages of the above-mentioned process, results in a lower cost, higher purity and yield of the prepared product, reducing the cost of using the product, broadening the application field of the product, and promoting the development of downstream industries. Attached Figure Description

[0035] To more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the specific embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0036] Figure 1The 1H-NMR spectrum of (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid obtained in Example 4. Detailed Implementation

[0037] The embodiments and examples of the present invention will be described in detail below with reference to the implementation methods and examples. However, those skilled in the art will understand that the following implementation methods and examples are only for illustrating the present invention and should not be regarded as limiting the scope of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0038] The first aspect of this invention provides a process for preparing (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid. Under alkaline conditions, a halophosphonate compound is added to a 3,6-dimethoxy-9H-carbazole solution for reaction. After the reaction is completed, hydrochloric acid aqueous solution is added for acid degreasing. Finally, extraction, reflux adsorption, and pulping purification are performed to obtain (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid.

[0039] The process provided by this invention uses 3,6-dimethoxy-9H-carbazole as the starting material and achieves the synthesis of the target product through a one-pot reaction. The reaction conditions are mild, the raw materials used are non-toxic and readily available, the synthesis process is simple, convenient to operate, and the separation yield is high. The use of hydrochloric acid aqueous solution for acid deesterification not only avoids the cumbersome post-treatment process of traditional liquid alkaline hydrolysis but also solves the problem of incomplete hydrolysis of diethyl phosphate under alkaline conditions, thereby significantly improving the purity of the synthesized product and making it more suitable for scale-up production.

[0040] Furthermore, the solvent used in the 3,6-dimethoxy-9H-carbazole solution includes dimethylformamide.

[0041] Preferably, the halophosphonate compound includes at least one of diethyl 2-bromoethylphosphonate, monoethyl bromoethylphosphonate, diethyl chloroethylphosphonate, and monoethyl chloroethylphosphonate.

[0042] Furthermore, the molar ratio of 3,6-dimethoxy-9H-carbazole to halophosphonate compounds is 1:1 to 3, preferably 1:1.5 to 2.8.

[0043] Typically, but not limitingly, the molar ratio of 3,6-dimethoxy-9H-carbazole to the halophosphonate compound can be 1:1, 1:1.2, 1:1.4, 1:1.6, 1:1.8, 1:2, 1:2.2, 1:2.4, 1:2.6, 1:2.8 or 3:1, or any value within the range of 1:1 to 3; preferred molar ratios can be 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:1.9, 1:2, 1:2.1, 1:2.2, 1:2.3, 1:2.4, 1:2.5, 1:2.6, 1:2.7 or 1:2.8, or any value within the range of 1:1.5 to 2.8.

[0044] Preferably, a solid alkali is added to create alkaline conditions.

[0045] Preferably, the solid alkali includes at least one of potassium hydroxide, potassium tert-butoxide, and sodium hydroxide, with potassium hydroxide being the most preferred.

[0046] Preferably, the amount of the solid alkali added is 1.5 to 3.5 times the molar amount of 3,6-dimethoxy-9H-carbazole, and more preferably 1.8 to 3 times.

[0047] Typically, but not limitingly, the amount of solid base added can be 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, or 3 times the molar amount of 3,6-dimethoxy-9H-carbazole, or any proportion within the range of 1.5 to 3.5. More preferably, the amount of solid base added can be 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, or 3 times the molar amount of 3,6-dimethoxy-9H-carbazole, or any proportion within the range of 1.8 to 3 times.

[0048] Furthermore, the reaction temperature is -10 to 60°C, preferably 0 to 30°C.

[0049] Typically, but not limitingly, the reaction temperature can be specifically -10℃, -5℃, 0℃, 5℃, 10℃, 15℃, 20℃, 25℃, 30℃, 35℃, 40℃, 45℃, 50℃, or 60℃, or any temperature value within the range of -10℃ to 60℃; the preferred reaction temperature can be specifically 0℃, 5℃, 10℃, 15℃, 20℃, 25℃, or 30℃, or any temperature value within the range of 0℃ to 30℃.

[0050] Preferably, the reaction time is 3 to 10 hours, and more preferably 4 to 8 hours.

[0051] Typically, but not limitingly, the reaction time can be in the range of 3h to 10h, more preferably in the range of 4h to 8h. Typically, but not limitingly, the reaction time can specifically be 3h, 4h, 5h, 6h, 7h, 8h, 9h, or 10h, or any time value within the range of 3h to 10h; and more preferably, the reaction time can specifically be 4h, 5h, 6h, 7h, or 8h, or any time value within the range of 4h to 8h.

[0052] Furthermore, the acid degreasing process is as follows: under liquid chromatography monitoring, the reaction system is heated and refluxed in an aqueous hydrochloric acid solution for hydrolysis.

[0053] Preferably, the concentration of the hydrochloric acid aqueous solution is 3-6 M.

[0054] Typically, but not limitingly, the concentration of the hydrochloric acid aqueous solution can be in the range of 3M to 6M. Typically, but not limitingly, the concentration of the hydrochloric acid aqueous solution can specifically be 3M, 3.5M, 4M, 4.5M, 5M, 5.5M, or 6M, or any concentration value within the range of 3M to 6M.

[0055] Preferably, the heating and reflux time is 1 to 4 hours, more preferably 2 to 3 hours.

[0056] Typically, but not limitingly, the heating and reflux time can be 1h, 2h, 3h or 4h, or any time value within the range of 1h to 4h; more preferably, the heating and reflux time can be 2h or 3h, or any time value within the range of 2h to 3h.

[0057] Furthermore, the extractant used in the extraction includes chloroform.

[0058] Preferably, the feed liquid is extracted in batches using an extractant, and then the organic phase is collected.

[0059] Preferably, the amount of the extractant is 0.5 to 3 times the weight of the raw material liquid.

[0060] Typically, but not limitingly, the amount of extractant used can be 0.5, 1, 1.5, 2, 2.5, or 3 times the weight of the feed liquid, or any proportion within the range of 0.5 to 3 times.

[0061] Preferably, the extraction is performed 2 to 4 times.

[0062] Typically, but not restrictively, the number of extractions can be 2, 3, or 4.

[0063] Furthermore, the adsorbent used in the reflux adsorption includes activated carbon.

[0064] Preferably, an adsorbent is added to the organic phase for reflux adsorption, and then the filtrate is collected by filtration to obtain a pure organic phase.

[0065] Preferably, the amount of adsorbent added is 0.015 to 0.03 times the weight of the organic phase.

[0066] Furthermore, the pulping and purification process is as follows: a pulping solvent is added to the pure organic phase for pulping, and then cooled to precipitate (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid.

[0067] Furthermore, the pulping solvent includes petroleum ether.

[0068] Preferably, the mass of the pulping solvent is 3 to 5 times the mass of the pure organic phase.

[0069] Typically, but not limitingly, the mass of the pulping solvent can be 3, 3.5, 4, 4.5, or 5 times the mass of the pure organic phase, or any mass ratio within the range of 3 to 5 times.

[0070] Preferably, the cooling temperature is -5 to 20°C, and more preferably 0 to 5°C.

[0071] Typically, but not limitingly, the cooling temperature can be specifically -5°C, 0°C, 5°C, 10°C, 15°C, or 20°C, or any temperature value within the range of -5°C to 20°C; more preferably, the cooling temperature can be specifically 0°C, 1°C, 2°C, 3°C, 4°C, or 5°C, or any temperature value within the range of 0°C to 5°C.

[0072] In some embodiments of the present invention, when the halophosphonate compound is selected as diethyl 2-bromoethylphosphonate and the solvent is dimethylformamide, the reaction formula is as follows:

[0073]

[0074] A second aspect of the present invention provides a (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid, which is prepared by the process described above.

[0075] The (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid provided by this invention, due to the advantages of the above-mentioned process, results in a lower cost, higher purity and yield of the prepared product, reducing the cost of using the product, broadening the application field of the product, and promoting the development of downstream industries.

[0076] The present invention is further illustrated below with specific embodiments and comparative examples. However, it should be understood that these embodiments are merely for illustrative purposes and should not be construed as limiting the invention in any way. Unless otherwise specified, the raw materials used in the embodiments and comparative examples of the present invention were carried out under conventional conditions or conditions recommended by the manufacturer. Reagents or instruments used, unless otherwise specified, are all commercially available conventional products.

[0077] Example 1

[0078] This embodiment provides a preparation process for (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid, the process of which is as follows:

[0079] 1. First, add 3,6-dimethoxy-9H-carbazole (0.1 mol, 22.73 g), dimethylformamide (250 g), potassium hydroxide (0.2 mol, 13.2 g), and diethyl 2-bromoethylphosphonate (0.2 mol, 49.01 g) to the reaction flask and start stirring to maintain the temperature. The reaction time is 6 h, the reaction temperature is 30 °C, and TLC is used to monitor the reaction until the starting material spot disappears. After the reaction is completed, slowly add hydrochloric acid aqueous solution (3 M) dropwise over 1 h, and reflux for 2 h. The acidolysis process is monitored by liquid chromatography.

[0080] 2. After acid hydrolysis, the system was extracted three times with chloroform, each time using twice the mass of the system. The organic phases were combined after extraction, and 400-mesh activated carbon powder was added to the organic phase for reflux adsorption. After reflux adsorption, the adsorbent was removed by hot filtration. Finally, three times the mass of liquid petroleum ether was added to the filtrate for slurrying, and the mixture was slowly cooled to 4°C for 2 hours. The slowly precipitated solid was (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid. After filtration, the filter cake was dried under vacuum at 80°C for 6 hours, and the purity was determined by NMR. The final product was 27.9 g (98.5% purity), with a yield of 82%.

[0081] Example 2

[0082] This embodiment provides a preparation process for (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid, the process of which is as follows:

[0083] 1. First, add 3,6-dimethoxy-9H-carbazole (0.2 mol, 45.45 g), dimethylformamide (500 g), potassium hydroxide (0.4 mol, 26.4 g), and diethyl 2-bromoethylphosphonate (0.5 mol, 122.5 g) to the reaction flask and start stirring to maintain the temperature. The reaction time is 4 h, the reaction temperature is 30 °C, and TLC is used to monitor the reaction until the starting material spot disappears. After the reaction is completed, slowly add hydrochloric acid aqueous solution (3 M) dropwise over 1 h, and reflux for 3 h. The acidolysis process is monitored by liquid chromatography.

[0084] 2. After acid hydrolysis, the system was extracted twice with chloroform, each time using 1.5 times the system mass. The organic phases were combined after extraction, and 400-mesh activated carbon powder was added to the organic phase for reflux adsorption. After reflux adsorption, the adsorbent was removed by hot filtration. Finally, 4 times the mass of liquid petroleum ether was added to the filtrate for slurrying, and the mixture was slowly cooled to 4°C for 3 hours. The slowly precipitated solid was (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid. After filtration, the filter cake was dried under vacuum at 80°C for 8 hours, and the purity was determined by NMR. The final product was pure (58g, purity 98.2%), with a yield of 85%.

[0085] Example 3

[0086] This embodiment provides a preparation process for (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid, the process of which is as follows:

[0087] 1. First, add 3,6-dimethoxy-9H-carbazole (0.05 mol, 11.36 g), dimethylformamide (125 g), potassium hydroxide (0.15 mol, 9.9 g), and diethyl 2-bromoethylphosphonate (0.1 mol, 24.5 g) to the reaction flask and start stirring to maintain the temperature. The reaction time is 7.5 h, the reaction temperature is 0 °C, and TLC is used to monitor the reaction until the starting material spot disappears. After the reaction is completed, slowly add hydrochloric acid aqueous solution (5 M) dropwise over 1 h, and reflux for 2 h. The acidolysis process is monitored by liquid chromatography.

[0088] 2. After acid hydrolysis, the system was extracted three times with chloroform, each time using three times the mass of the system. The organic phases were combined after extraction, and 400-mesh activated carbon powder was added to the organic phase for reflux adsorption. After reflux adsorption, the adsorbent was removed by hot filtration. Finally, four times the mass of liquid petroleum ether was added to the filtrate for slurrying, and the mixture was slowly cooled to 2°C for 2 hours. The slowly precipitated solid was (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid. After filtration, the filter cake was dried under vacuum at 80°C for 8 hours, and the purity was determined by NMR. The final product was 14.9 g (98.9% purity), with a yield of 88%.

[0089] Example 4

[0090] This embodiment provides a preparation process for (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid, the process of which is as follows:

[0091] 1. First, add 0.5 mol (113.63 g) of 3,6-dimethoxy-9H-carbazole, 1250 g of dimethylformamide, 0.9 mol (59.4 g) of potassium hydroxide, and 1.25 mol (306.3 g) of diethyl 2-bromoethylphosphonate to a reaction flask and start stirring to maintain the temperature. The reaction time is 7 h, the reaction temperature is 15 °C, and TLC is used to monitor the reaction until the starting material spot disappears. After the reaction is completed, slowly add hydrochloric acid aqueous solution (4 M) dropwise over 1 h, and reflux for 3 h. The acidolysis process is monitored by liquid chromatography.

[0092] 2. After acid hydrolysis, the system was extracted four times with chloroform, each time using three times the mass of the system. The organic phases were combined after extraction, and 400-mesh activated carbon powder was added to the organic phase for reflux adsorption. After reflux adsorption, the adsorbent was removed by hot filtration. Finally, four times the mass of liquid petroleum ether was added to the filtrate for slurrying, and the mixture was slowly cooled to 0°C for 3 hours. The slowly precipitated solid was (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid. After filtration, the filter cake was dried under vacuum at 80°C for 4 hours, and the purity was determined by NMR. The final product was pure (136.9 g, purity 99.2%), with a yield of 81%.

[0093] Example 5

[0094] This embodiment provides a preparation process for (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid, the process of which is as follows:

[0095] 1. First, add 3,6-dimethoxy-9H-carbazole (0.25 mol, 56.8 g), dimethylformamide (625 g), potassium hydroxide (0.55 mol, 36.2 g), and diethyl 2-bromoethylphosphonate (1.25 mol, 306.3 g) to the reaction flask and start stirring to maintain the temperature. The reaction time is 8 h, the reaction temperature is 10 °C, and TLC is used to monitor the reaction until the starting material spot disappears. After the reaction is completed, slowly add hydrochloric acid aqueous solution (6 M) dropwise over 1 h, and reflux for 2 h. The acidolysis process is monitored by liquid chromatography.

[0096] 2. After acid hydrolysis, the system was extracted four times with chloroform, each time using four times the mass of the system. The organic phases were combined after extraction, and 400-mesh activated carbon powder was added to the organic phase for reflux adsorption. After reflux adsorption, the adsorbent was removed by hot filtration. Finally, five times the mass of liquid petroleum ether was added to the filtrate for slurrying, and the mixture was slowly cooled to 0°C for 4 hours. The slowly precipitated solid was (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid. After filtration, the filter cake was dried under vacuum at 80°C for 8 hours, and the purity was determined by NMR. The final product was 72.2 g (98.7% purity), with a yield of 85%.

[0097] Example 6

[0098] (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid was prepared using a method essentially the same as that in Example 1, except that the reaction temperature was 80°C; the other parameters, including the type and amount of raw materials and the preparation method, were the same as in Example 1.

[0099] After the reaction was completed, the product (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid (20.2 g, purity 56.3%) was obtained, with a yield of 34%.

[0100] Comparative Example 1

[0101] (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid was prepared using a method essentially the same as in Example 1, except that sodium hydroxide alkaline hydrolysis was used instead of acid hydrolysis; the remaining parameters, including the type and amount of raw materials and the preparation method, were the same as in Example 1.

[0102] The alkaline hydrolysis process is lengthy, complex, and time-consuming, which affects the yield. After the reaction, HPLC monitoring showed that only a small portion was converted into the target product. NMR verification showed that most of it was incompletely hydrolyzed monoethyl phosphate. The final product was (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid (7.4g, purity 68%), with a yield of 15%.

[0103] Comparative Example 2

[0104] The method used was basically the same as in Example 3 (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid, except that potassium carbonate was used instead of potassium hydroxide; the other parameters, including the type and amount of raw materials and the preparation method, were the same as in Example 3.

[0105] After the first step of the reaction was completed, no progress of the target reaction was detected.

[0106] Characterization example

[0107] The (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid obtained in Example 4 was subjected to H-NMR spectra, and the resulting spectra are shown below. Figure 1 As shown.

[0108] from Figure 1 It can be seen that, 1 H NMR (400MHz, DMSO-d6) δ7.72(d,J=2.2Hz,2H),7.39(d,J=8.8Hz,2H),7.07(dd,J=8.8,2.3Hz,2H),4.44(dd,2H),3.85(s,6H),1.96(m,2H).

[0109] The NMR spectrum was clear and free of impurities, and consistent with the standard spectrum, indicating the successful synthesis of (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid.

[0110] 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 or all of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A process for preparing (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid, characterized in that, Under alkaline conditions, a halophosphonate compound was added to a 3,6-dimethoxy-9H-carbazole solution for reaction. After the reaction was completed, hydrochloric acid aqueous solution was added for acid degreasing. Finally, extraction, reflux adsorption, and pulping purification were performed to obtain (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid. The halophosphonate compounds include at least one of diethyl 2-bromoethylphosphonate, monoethyl bromoethylphosphonate, diethyl chloroethylphosphonate, and monoethyl chloroethylphosphonate. An alkaline condition is created by adding a solid base, said solid base including at least one of potassium hydroxide, potassium tert-butoxide, and sodium hydroxide.

2. The process method according to claim 1, characterized in that, The solvent used in the 3,6-dimethoxy-9H-carbazole solution includes dimethylformamide.

3. The process method according to claim 1, characterized in that, The molar ratio of 3,6-dimethoxy-9H-carbazole to halophosphonate compounds is 1:1~3.

4. The process method according to claim 1, characterized in that, The molar ratio of 3,6-dimethoxy-9H-carbazole to halophosphonate compounds is 1:1.5~2.

8.

5. The process method according to claim 1, characterized in that, The solid alkali is potassium hydroxide.

6. The process method according to claim 1, characterized in that, The amount of the solid base added is 1.5 to 3.5 times the molar amount of 3,6-dimethoxy-9H-carbazole.

7. The process method according to claim 1, characterized in that, The amount of the solid base added is 1.8 to 3 times the molar amount of 3,6-dimethoxy-9H-carbazole.

8. The process method according to claim 1, characterized in that, The reaction temperature is -10~60℃.

9. The process method according to claim 1, characterized in that, The reaction temperature is 0~30℃.

10. The process method according to claim 1, characterized in that, The reaction time is 3 to 10 hours.

11. The process method according to claim 1, characterized in that, The reaction time is 4-8 hours.

12. The process method according to claim 1, characterized in that, The acid-cleansing and fat-removing process is as follows: Under liquid chromatography monitoring, the reaction system was hydrolyzed by reflux in hydrochloric acid aqueous solution.

13. The process method according to claim 12, characterized in that, The concentration of the hydrochloric acid aqueous solution is 3~6M.

14. The process method according to claim 12, characterized in that, The heating and reflux time is 1 to 4 hours.

15. The process method according to claim 12, characterized in that, The heating and reflux time is 2-3 hours.

16. The process method according to any one of claims 1 to 15, characterized in that, The extraction process uses chloroform as an extractant.

17. The process method according to any one of claims 1 to 15, characterized in that, The feed liquid was extracted in batches using an extractant, and then the organic phase was collected.

18. The process method according to claim 17, characterized in that, The amount of the extractant used is 0.5 to 3 times the weight of the raw material liquid.

19. The process method according to any one of claims 1 to 15, characterized in that, The extraction is performed 2 to 4 times.

20. The process method according to claim 16, characterized in that, The adsorbent used in the reflux adsorption includes activated carbon.

21. The process method according to claim 16, characterized in that, An adsorbent is added to the organic phase for reflux adsorption, and then the filtrate is collected by filtration to obtain a pure organic phase.

22. The process method according to claim 21, characterized in that, The amount of adsorbent added is 0.015 to 0.03 times the weight of the organic phase.

23. The process method according to claim 20, characterized in that, The pulping and purification process is as follows: A slurrying solvent was added to the pure organic phase for slurrying, and then cooled to precipitate (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid.

24. The process method according to claim 23, characterized in that, The pulping solvent includes petroleum ether.

25. The process method according to claim 23, characterized in that, The mass of the pulping solvent is 3 to 5 times the mass of the pure organic phase.

26. The process method according to claim 23, characterized in that, The cooling temperature is -5~20℃.

27. The process method according to claim 23, characterized in that, The cooling temperature is 0~5℃.

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