Process method for preparing (2-(3, 6-dimethoxy-9H-carbazole-9-yl) ethyl) phosphonic acid

Abstract

The invention provides a process method for preparing (2-(3, 6-dimethoxy-9H-carbazole-9-yl) ethyl) phosphonic acid, and particularly relates to the technical field of organic synthesis. The process method comprises the following steps: under an alkaline condition, adding a halogenated phosphonate compound into a 3, 6-dimethoxy-9H-carbazole solution for reaction, after the reaction is finished, adding a hydrochloric acid aqueous solution for acidolysis degreasing, and finally extracting, refluxing, adsorbing, pulping and purifying to obtain the (2-(3, 6-dimethoxy-9H-carbazole-9-yl) ethyl) phosphonic acid. According to the process method, 3, 6-dimethoxy-9H-carbazole is adopted as a starting material, synthesis of a target product is achieved through a one-pot reaction, reaction conditions are mild, used raw materials are non-toxic and easy to obtain, the synthesis process is simple, operation is convenient and fast, and the separation yield is high.

Description

Technical Field

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

[0002] Perovskite cells are a new type of solar cell, which consists of a multilayer film with perovskite crystals as the main material. Due to its large carrier diffusion length and suitable bandgap width, perovskite cells have quickly become a hot spot in photovoltaic research, and have two key advantages: low economic cost and high optimal conversion efficiency. In recent years, self-assembled monolayers (SAM materials) have received great attention as an ideal hole transport layer material.

[0003] Among them, (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid is a type of carbazole-derived SAM material containing a phosphoric acid group, which plays an important role in the uniform formation and performance improvement of perovskite films. At present, the direct preparation method of this monomer mainly uses carbazole and its derivatives and disubstituted halogenated alkanes as starting materials, and after alkylation, extraction, drying and dehydration, concentration, recrystallization and other steps, it reacts with triethyl phosphite, and finally deesterifies and adjusts the acid under alkaline conditions to finally obtain the target product. However, this synthesis route has the following disadvantages: expensive raw materials, complicated and lengthy operation steps, incomplete alkaline hydrolysis of ethyl phosphate, harsh reaction conditions, etc., resulting in high costs and difficulty in equipment selection, which is not conducive to large-scale quantitative production.

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

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

[0006] The second object of the present invention is to provide a (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid.

[0007] In order to achieve the above-mentioned purpose of the present invention, the following technical solutions are particularly adopted:

[0008] The first aspect of the present invention provides a process for preparing (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid. Under alkaline conditions, a halogenated phosphonate compound is added to a 3,6-dimethoxy-9H-carbazole solution for reaction. After the reaction, a 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 halogenated phosphonate 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 the halogenated phosphonate compound is 1:1-3, preferably 1:1.5-2.8.

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

[0013] Preferably, the solid base comprises at least one of potassium hydroxide, potassium tert-butoxide and sodium hydroxide, preferably potassium hydroxide.

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

[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, preferably 4 to 8 hours.

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

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

[0019] Preferably, the temperature rising and refluxing time is 1 to 4 hours, preferably 2 to 3 hours.

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

[0021] Preferably, the raw material solution is extracted in batches using an extractant, and then the organic phase is collected.

[0022] Preferably, the amount of the extractant used 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 to perform the reflux adsorption, and then the filtrate is collected by filtration to obtain a pure organic phase.

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

[0027] Furthermore, the pulping and purification process is: adding a pulping solvent to the pure organic phase for pulping, and then cooling and precipitating to obtain (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, preferably 0 to 5°C.

[0031] The 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 method.

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

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

[0034] The (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid provided by the present invention, in view of the advantages of the above-mentioned process method, enables the prepared product to have lower cost, higher purity and yield, reduces the use cost of the product, broadens the use field of the product, and promotes the development of downstream industries. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] In order to more clearly illustrate the specific implementation methods of the present invention or the technical solutions in the prior art, the drawings required for use in the specific implementation methods or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some implementation methods of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0036] Figure 1This is the H-NMR spectrum of (2-(3,6-dimethoxy-9H-carbazol-9-yl)ethyl)phosphonic acid obtained in Example 4. DETAILED DESCRIPTION

[0037] The embodiments of the present invention will be described in detail below in conjunction with the embodiments and examples, but those skilled in the art will understand that the following embodiments and examples are only used to illustrate the present invention and should not be considered to limit the scope of the present invention. Based on the embodiments in the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0038] The first aspect of the present invention provides a process for preparing (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid. Under alkaline conditions, a halogenated phosphonate compound is added to a 3,6-dimethoxy-9H-carbazole solution for reaction. After the reaction, a 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 the present invention adopts 3,6-dimethoxy-9H-carbazole as a starting material, realizes the synthesis of a target product through a one-pot reaction, has mild reaction conditions, uses non-toxic and easily available raw materials, has a simple synthesis process, is convenient to operate, and has a high separation yield. The use of hydrochloric acid aqueous solution for acid deesterification not only avoids the cumbersome post-treatment process of traditional liquid alkali hydrolysis, but also solves the problem of incomplete hydrolysis of diethyl phosphate under alkaline conditions, thereby significantly improving the purity of the synthetic product and being more conducive to scale-up production.

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

[0041] Preferably, the halogenated phosphonate 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 the halogenated phosphonate compound is 1:1-3, preferably 1:1.5-2.8.

[0043] Typically but not limiting, the molar ratio of 3,6-dimethoxy-9H-carbazole to the halogenated phosphonate 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 in the range of 1:1 to 3; the preferred molar ratio 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 in the range of 1:1.5 to 2.8.

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

[0045] Preferably, the solid base comprises at least one of potassium hydroxide, potassium tert-butoxide and sodium hydroxide, preferably potassium hydroxide.

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

[0047] Typically but not limiting, the amount of solid base added can be 1.5 times, 1.6 times, 1.7 times, 1.8 times, 1.9 times, 2 times, 2.1 times, 2.2 times, 2.3 times, 2.4 times, 2.5 times, 2.6 times, 2.7 times, 2.8 times, 2.9 times, 3 times of the molar amount of 3,6-dimethoxy-9H-carbazole, or any ratio within the range of 1.5 to 3.5; more preferably, the amount of solid base added can be 1.8 times, 1.9 times, 2 times, 2.1 times, 2.2 times, 2.3 times, 2.4 times, 2.5 times, 2.6 times, 2.7 times, 2.8 times, 2.9 times or 3 times of the molar amount of 3,6-dimethoxy-9H-carbazole, or any ratio 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 limiting, the reaction temperature can be specifically -10°C, -5°C, 0°C, 5°C, 10°C, 15°C, 20°C, 25°C, 30°C, 35°C, 40°C, 45°C, 50°C or 60°C, or any temperature value in the range of -10°C to 60°C; the preferred reaction temperature can be specifically 0°C, 5°C, 10°C, 15°C, 20°C, 25°C or 30°C, or any temperature value in the range of 0°C to 30°C.

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

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

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

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

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

[0055] Preferably, the temperature rising and refluxing time is 1 to 4 hours, preferably 2 to 3 hours.

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

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

[0058] Preferably, the raw material solution is extracted in batches using an extractant, and then the organic phase is collected.

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

[0060] Typically but not limiting, the amount of the extractant used can be 0.5 times, 1 times, 1.5 times, 2 times, 2.5 times or 3 times the weight of the raw material solution, or any ratio within the range of 0.5 times to 3 times.

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

[0062] Typically, but not limiting, the number of extractions may be 2, 3 or 4 times.

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

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

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

[0066] Furthermore, the pulping and purification process is: adding a pulping solvent to the pure organic phase for pulping, and then cooling and precipitating to obtain (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 limiting, the mass of the slurry solvent can be 3 times, 3.5 times, 4 times, 4.5 times 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, preferably 0 to 5°C.

[0071] Typically but not restrictively, the cooling temperature may be -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; and a more preferred cooling temperature may be 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 halogenated phosphonate compound is diethyl 2-bromoethylphosphonate and the solvent is dimethylformamide, the reaction formula is as follows:

[0073]

[0074] The 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 method.

[0075] The (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid provided by the present invention, in view of the advantages of the above-mentioned process method, enables the prepared product to have lower cost, higher purity and yield, reduces the use cost of the product, broadens the use field of the product, and promotes the development of downstream industries.

[0076] The present invention is further described below by specific examples and comparative examples, but it should be understood that these examples are only used for more detailed description and should not be understood as limiting the present invention in any form. The raw materials used in the examples and comparative examples of the present invention, if no specific conditions are specified, are carried out according to conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used without specifying the manufacturer are all conventional products that can be purchased commercially.

[0077] Example 1

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

[0079] 1. First, add 3,6-dimethoxy-9H-carbazole (0.1mol, 22.73g), dimethylformamide (250g), potassium hydroxide (0.2mol, 13.2g), and diethyl 2-bromoethylphosphonate (0.2mol, 49.01g) into the reaction bottle and stir to keep warm. The reaction time is 6h, the reaction temperature is 30℃, and TLC tracking is performed until the raw material point disappears. After the reaction is completed, slowly add hydrochloric acid aqueous solution (3M) within 1h, heat and reflux for 2h, and monitor the acid hydrolysis process by liquid chromatography.

[0080] 2. After the acid hydrolysis, the system was extracted with chloroform for 3 times, and the amount of chloroform used each time was 2 times the mass of the system. After extraction, the organic phases were combined, and 400 mesh activated carbon powder was added to the organic phase for reflux adsorption. After the reflux adsorption was completed, the adsorbent was removed by hot filtration. Finally, 3 times the mass of liquid petroleum ether was added to the filtrate for pulping, and slowly cooled to 4°C for 2 hours. The solid was slowly precipitated, which was (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid. After filtration, the filter cake was vacuum dried at 80°C for 6 hours and then the purity was detected by nuclear magnetic resonance. Finally, the pure product (27.9g, purity 98.5%) was obtained with a yield of 82%.

[0081] Example 2

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

[0083] 1. First, add 3,6-dimethoxy-9H-carbazole (0.2mol, 45.45g), dimethylformamide (500g), potassium hydroxide (0.4mol, 26.4g), and diethyl 2-bromoethylphosphonate (0.5mol, 122.5g) into the reaction bottle and stir to keep warm. The reaction time is 4h, the reaction temperature is 30℃, and TLC tracking is performed until the raw material point disappears. After the reaction is completed, slowly add hydrochloric acid aqueous solution (3M) within 1h, heat and reflux for 3h, and monitor the acid hydrolysis process by liquid chromatography.

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

[0085] Example 3

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

[0087] 1. First, add 3,6-dimethoxy-9H-carbazole (0.05mol, 11.36g), dimethylformamide (125g), potassium hydroxide (0.15mol, 9.9g), and diethyl 2-bromoethylphosphonate (0.1mol, 24.5g) into the reaction bottle and stir to keep warm. The reaction time is 7.5h, the reaction temperature is 0℃, and TLC tracking is performed until the raw material point disappears. After the reaction is completed, slowly add hydrochloric acid aqueous solution (5M) within 1h, heat and reflux for 2h, and monitor the acid hydrolysis process by liquid chromatography.

[0088] 2. After the acid hydrolysis, the system was extracted with chloroform for 3 times, and the amount of chloroform used each time was 3 times the mass of the system. After extraction, the organic phases were combined, and 400 mesh activated carbon powder was added to the organic phase for reflux adsorption. After the reflux adsorption was completed, the adsorbent was removed by hot filtration. Finally, 4 times the mass of liquid petroleum ether was added to the filtrate for pulping, and slowly cooled to 2°C for 2 hours. The solid was slowly precipitated, which was (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid. After filtration, the filter cake was vacuum dried at 80°C for 8 hours and then the purity was detected by nuclear magnetic resonance. Finally, the pure product (14.9g, purity 98.9%) was obtained with a yield of 88%.

[0089] Example 4

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

[0091] 1. First, add 3,6-dimethoxy-9H-carbazole (0.5 mol, 113.63 g), dimethylformamide (1250 g), potassium hydroxide (0.9 mol, 59.4 g), and diethyl 2-bromoethylphosphonate (1.25 mol, 306.3 g) into the reaction bottle and stir to keep warm. The reaction time is 7 h, the reaction temperature is 15 ° C, and TLC tracking is performed until the raw material point disappears. After the reaction is completed, slowly add hydrochloric acid aqueous solution (4 M) within 1 h, heat and reflux for 3 h, and monitor the acidolysis process by liquid chromatography.

[0092] 2. After the acid hydrolysis, the system was extracted with chloroform for 4 times, and the amount of chloroform used each time was 3 times the mass of the system. After extraction, the organic phases were combined, and 400 mesh activated carbon powder was added to the organic phase for reflux adsorption. After the reflux adsorption was completed, the adsorbent was removed by hot filtration. Finally, 4 times the mass of liquid petroleum ether was added to the filtrate for pulping, and slowly cooled to 0°C for 3 hours. The solid was slowly precipitated, which was (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid. After filtration, the filter cake was vacuum dried at 80°C for 4 hours and then the purity was detected by nuclear magnetic resonance. Finally, the pure product (136.9g, purity 99.2%) was obtained, and the yield was 81%.

[0093] Example 5

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

[0095] 1. First, add 3,6-dimethoxy-9H-carbazole (0.25mol, 56.8g), dimethylformamide (625g), potassium hydroxide (0.55mol, 36.2g), and diethyl 2-bromoethylphosphonate (1.25mol, 306.3g) into the reaction bottle and stir to keep warm. The reaction time is 8h, the reaction temperature is 10℃, and TLC tracking is performed until the raw material point disappears. After the reaction is completed, slowly add hydrochloric acid aqueous solution (6M) within 1h, heat and reflux for 2h, and monitor the acid hydrolysis process by liquid chromatography.

[0096] 2. After the acid hydrolysis, the system was extracted with chloroform for 4 times, and the amount of chloroform used each time was 4 times the mass of the system. After extraction, the organic phases were combined, and 400 mesh activated carbon powder was added to the organic phase for reflux adsorption. After the reflux adsorption was completed, the adsorbent was removed by hot filtration. Finally, 5 times the mass of liquid petroleum ether was added to the filtrate for pulping, and slowly cooled to 0°C for 4 hours. The solid was slowly precipitated, which was (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid. After filtration, the filter cake was vacuum dried at 80°C for 8 hours and then the purity was detected by nuclear magnetic resonance. Finally, the pure product (72.2g, purity 98.7%) was obtained with a yield of 85%.

[0097] Example 6

[0098] (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid was prepared by a method substantially the same as in Example 1, except that the reaction temperature was 80° C.; the remaining parameters, including the type of raw materials, the amount used, 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 by a method substantially the same as in Example 1, except that sodium hydroxide alkaline solution was used for hydrolysis instead of acid hydrolysis; the remaining parameters, including the type of raw materials, the amount used, and the preparation method, were the same as in Example 1.

[0102] The entire operation process of the alkaline hydrolysis process has lengthy process steps, complicated operations, long time consumption, and affects the yield. After the reaction is completed, HPLC monitoring found that only a small part of it was converted into the target product. Nuclear magnetic resonance verification confirmed that most of it was incompletely hydrolyzed monoethyl phosphate products. The final product (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid (7.4 g, purity 68%), the yield was 15%.

[0103] Comparative Example 2

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

[0105] After the first step of the reaction was completed, no 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 spectrum. The spectrum obtained was as follows: Figure 1 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, which was consistent with the standard spectrum. (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid was successfully synthesized.

[0110] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or replace some or all of the technical features therein with equivalents. However, these modifications or replacements 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 halogenated phosphonate compound is added to a 3,6-dimethoxy-9H-carbazole solution to react, and after the reaction, a hydrochloric acid aqueous solution is added to carry out acid degreasing, and finally extraction, reflux adsorption, and beating purification are performed to obtain (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid.

2. The process according to claim 1, characterized in that: In the 3,6-dimethoxy-9H-carbazole solution, the solvent used includes dimethylformamide; Preferably, the halogenated phosphonate compound includes at least one of diethyl 2-bromoethylphosphonate, monoethyl bromoethylphosphonate, diethyl chloroethylphosphonate, and monoethyl chloroethylphosphonate.

3. The process according to claim 1, characterized in that: The molar ratio of 3,6-dimethoxy-9H-carbazole to the halogenated phosphonate compound is 1:1 to 3, preferably 1:1.5 to 2.8; Preferably, a solid base is added to create alkaline conditions; Preferably, the solid base comprises at least one of potassium hydroxide, potassium tert-butoxide and sodium hydroxide, preferably potassium hydroxide; Preferably, the amount of the solid base added is 1.5 to 3.5 times, preferably 1.8 to 3 times, the molar amount of 3,6-dimethoxy-9H-carbazole.

4. The process according to claim 1, characterized in that: The reaction temperature is -10 to 60°C, preferably 0 to 30°C; Preferably, the reaction time is 3 to 10 hours, preferably 4 to 8 hours.

5. The process according to claim 1, characterized in that: The process of acid degreasing is: Under the monitoring of liquid chromatography, the reaction system was heated and refluxed in a hydrochloric acid aqueous solution for hydrolysis; Preferably, the concentration of the hydrochloric acid aqueous solution is 3 to 6 M; Preferably, the temperature rising and refluxing time is 1 to 4 hours, preferably 2 to 3 hours.

6. The process according to any one of claims 1 to 5, characterized in that: The extraction agent used in the extraction includes chloroform; Preferably, the raw material solution is extracted in batches using an extractant, and then the organic phase is collected; Preferably, the amount of the extractant is 0.5 to 3 times the weight of the raw material liquid; Preferably, the extraction is performed 2 to 4 times.

7. The process according to claim 6, characterized in that: The adsorbent used in the reflux adsorption includes activated carbon; Preferably, an adsorbent is added to the organic phase to perform the reflux adsorption, and then the filtrate is collected by filtration to obtain a pure organic phase; Preferably, the amount of the adsorbent added is 0.015 to 0.03 times the weight of the organic phase.

8. The process according to claim 7, characterized in that: The process of pulping and purification is as follows: A slurrying solvent is added to the pure organic phase for slurrying, and then cooled and precipitated to obtain (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid.

9. The process according to claim 8, characterized in that: The pulping solvent includes petroleum ether; Preferably, the mass of the pulping solvent is 3 to 5 times the mass of the pure organic phase; Preferably, the cooling temperature is -5 to 20°C, preferably 0 to 5°C.

10. A (2-(3,6-dimethoxy-9H-carbazole-9-yl)ethyl)phosphonic acid, characterized in that The product is prepared by the process described in any one of claims 1 to 9.

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