A method for preparing 3-hydroxyphthalic anhydride

Abstract

The present invention discloses a preparation method of 3-hydroxyphthalic anhydride, which relates to the technical field of organic synthesis. Using 3-nitrophthalic acid as the starting reaction material, the raw materials are inexpensive and easily available. By optimizing the process route, the reduction and cyclization steps are combined into one step, and then two steps of diazotization and hydrolysis are carried out without additional pre-purification treatment of the process products. Compared with the traditional method, the synthesis method of the present invention has fewer reaction steps, a simple process and is easy to operate, and has low requirements for production equipment; the reaction conditions are mild and easy to achieve, which is more conducive to industrial scale-up production and has better industrial application prospects.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthesis, and in particular, to a method for preparing 3-hydroxyphthalic anhydride. Background Art

[0002] 3-Hydroxyphthalic anhydride, also known as 3-hydroxyphthalic anhydride and hydroxyphthalic anhydride, is one of the important organic chemical raw materials. Its main derivatives include dibutyl phthalate, dioctyl phthalate, and diisobutyl phthalate, etc., which can be used as plasticizers for PVC, etc.; it can also be used in the production of unsaturated polyester resins, alkyd resins, dyes and pigments, various paints, food additives, the laxative phenolphthalein in medicine, phosmet and bentazone in pesticides, and saccharin sodium, etc. It can also be used as an epoxy resin curing agent and an analytical reagent, etc., and has a very wide range of applications and is an important fine chemical. In addition, 3-hydroxyphthalic anhydride can also be used in the preparation of active substances for modifying the in vitro activity of ovalbumin against HPV, HIV, herpes simplex virus, etc. This potential active substance drug is expected to become a new drug for hunting microorganisms for preventing diseases. This key pharmaceutical intermediate has broad application prospects.

[0003] 3-Hydroxyphthalic anhydride belongs to a new type of fine chemical. The traditional production method has problems such as complex processes and high equipment costs. Compared with the huge production capacity of downstream related products, the production capacity of 3-hydroxyphthalic anhydride is significantly insufficient.

[0004] Currently reported synthesis routes of 3-hydroxyphthalic anhydride generally have the following problems:

[0005] (1) The reaction process route is long, the reaction system is complex, the operation is cumbersome, and the yield is low;

[0006] (2) The catalyst is expensive, the dosage is large, and the starting materials are difficult to obtain;

[0007] (3) The reaction conditions are harsh, there are certain safety hazards, and the requirements for equipment and processes are relatively high.

[0008] In view of this, the present invention is specifically proposed. Summary of the Invention

[0009] The purpose of the present invention is to provide a method for preparing 3-hydroxyphthalic anhydride, aiming to provide a synthesis method with fewer reaction steps, mild conditions, and easy industrial scale-up production on the premise of ensuring the yield of the target product.

[0010] The present invention is implemented as follows:

[0011] In a first aspect, the present invention provides a method for preparing 3-hydroxyphthalic anhydride, comprising: reducing 3-nitrophthalic acid in the presence of a palladium-carbon catalyst, reacting with a dehydrating agent after the reaction to obtain a reaction solution, concentrating the reaction solution to obtain a solid material, and performing diazotization hydrolysis on the solid material in the presence of sodium nitrite to obtain the target product. The reaction route is as follows:

[0012]

[0013] In an alternative embodiment, the process of preparing the solid material includes: mixing 3-nitrophthalic acid, an inorganic base, an organic solvent and a palladium-carbon catalyst, then dropping a reducing agent to react, controlling the reaction temperature at 30°C - 50°C, the reaction time at 1h - 5h, mixing and reacting with a dehydrating agent after the reaction is completed, taking the supernatant for solid-liquid separation after the reaction is completed to obtain a reaction solution, and concentrating the reaction solution to obtain a solid material;

[0014] Preferably, the organic solvent is selected from toluene.

[0015] In an alternative embodiment, the mass ratio of the amount of the palladium-carbon catalyst to the mass of 3-nitrophthalic acid is 0.1 - 3.5:100, preferably 0.5 - 2:100.

[0016] In an alternative embodiment, the inorganic base is selected from at least one of potassium hydroxide and sodium hydroxide;

[0017] Preferably, the molar ratio of 3-nitrophthalic acid to the inorganic base is 1:2 - 3; more preferably 1:2 - 2.5.

[0018] In an alternative embodiment, the reducing agent is hydrazine hydrate, and the molar ratio of the reducing agent to 3-nitrophthalic acid is 2 - 4:1, preferably 2.5 - 3.5:1.

[0019] In an alternative embodiment, the dehydrating agent is selected from at least one of polyphosphoric acid, concentrated sulfuric acid and phosphorus pentoxide;

[0020] Preferably, the molar ratio of the dehydrating agent to 3-nitrophthalic acid is 20 - 40:1, more preferably 25 - 35:1.

[0021] In an alternative embodiment, after the reduction reaction is completed, it is mixed with a dehydrating agent, heated to reflux for 1h - 3h, and tracked by liquid chromatography until the reaction is complete;

[0022] Preferably, the reflux time is 1.5h - 2.5h.

[0023] In an alternative embodiment, a solid material, water, and an inorganic acid are mixed, and then a sodium nitrite solution is added dropwise for reaction. The reaction temperature is controlled at 0°C - 5°C, and the reaction time is 1 h - 3 h. Then, the temperature is raised to 30°C - 50°C and held for 2 h - 6 h;

[0024] Preferably, during the addition of the sodium nitrite solution for reaction, the reaction temperature is controlled at 0°C - 3°C, the reaction time is 2 h - 3 h, and the holding time is 3 h - 5 h.

[0025] In an alternative embodiment, the molar ratio of sodium nitrite to 3-nitrophthalic acid is 1.5 - 1.8:1;

[0026] Preferably, the inorganic acid is selected from at least one of concentrated sulfuric acid and concentrated hydrochloric acid;

[0027] Preferably, the molar ratio of the inorganic acid to 3-nitrophthalic acid is 8 - 11:1.

[0028] In an alternative embodiment, it further includes: after the holding is completed, extraction is carried out. The obtained organic phase is concentrated and dried to obtain a crude product, and the crude product is recrystallized;

[0029] Preferably, the extraction is carried out multiple times with ethyl acetate, and the organic phases are combined. The amount of ethyl acetate used for each extraction is in a mass ratio of 0.3 - 1:1 to the reaction solution; more preferably, the number of extractions is 3 - 6 times, and further preferably 3 - 4 times;

[0030] Preferably, the drying temperature is 70°C - 90°C, and the drying time is 6 h - 10 h;

[0031] Preferably, recrystallization is carried out using acetone.

[0032] The present invention has the following beneficial effects: Using 3-nitrophthalic acid as the starting reaction material, the raw materials are inexpensive and easily available. By optimizing the process route, the reduction and cyclization steps are combined into one step, and then through two steps of diazotization and hydrolysis reactions, there is no need to perform additional pre-purification treatment on the process products. Compared with the traditional method, the synthesis method of the present invention has fewer reaction steps, a simple process and is easy to operate, and has low requirements for production equipment; the reaction conditions are mild and easy to achieve, which is more conducive to industrial scale-up production and has better industrial application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following will briefly introduce the drawings required for use in the embodiments. It should be understood that the following drawings only show some embodiments of the present invention, and therefore should not be regarded as limiting the scope. For those of ordinary skill in the art, other related drawings can also be obtained based on these drawings without creative efforts.

[0034] Figure 1 1H NMR spectrum of the product prepared in Example 1;

[0035] Figure 2 Liquid chromatography detection chart of the product prepared in Example 1. Detailed implementation manners

[0036] To make the objectives, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. For those conditions not specified in the embodiments, they are carried out according to conventional conditions or conditions recommended by the manufacturer. For reagents or instruments whose manufacturers are not specified, they are all conventional products that can be obtained through commercial purchase.

[0037] An embodiment of the present invention provides a preparation method of 3-hydroxyphthalic anhydride, and its synthesis route is as follows:

[0038]

[0039] It should be noted that using 3-nitrophthalic acid as the starting reaction material, the raw materials are inexpensive and easily available. By optimizing the process route, the reduction and cyclization steps are combined in one step, and then the target product is obtained through diazotization hydrolysis.

[0040] Specifically, the preparation method includes the following steps:

[0041] S1. Reduction and cyclization

[0042] Reduce 3-nitrophthalic acid in the presence of palladium-carbon catalyst. After the reaction is completed, react with a dehydrating agent to obtain a reaction solution, and concentrate the reaction solution to obtain a solid material. Using inexpensive 3-nitrophthalic acid as the starting material, the reduction and cyclization steps are combined in one step, without additional pre-purification treatment of the process products, which is convenient for operation.

[0043] It should be noted that the present invention selects palladium-carbon as the catalyst, which has high reaction activity, small dosage, fast reaction speed, and can be recycled by filtration after the reaction, and the activity has no obvious attenuation.

[0044] In some embodiments, the process of preparing the solid material includes: mixing 3-nitrophthalic acid, inorganic base, organic solvent and palladium-carbon catalyst, then dropping a reducing agent to react. After the dropping is completed, the reaction time is 1 h - 5 h, control the reaction temperature at 30°C - 50°C. After the reaction is completed, mix with a dehydrating agent to react. After the reaction is completed, take the supernatant for solid-liquid separation to obtain a reaction solution, and concentrate the reaction solution to obtain a solid material. The way of solid-liquid separation is not limited, it can be general filtration. The catalyst palladium-carbon is recycled and reused, and the filtrate (i.e., the reaction solution) is concentrated to obtain a solid material.

[0045] The organic solvent can be toluene; the inorganic base is selected from at least one of potassium hydroxide and sodium hydroxide, and can be any one or several of the above.

[0046] In some embodiments, the mass ratio of the amount of palladium-carbon catalyst to 3-nitrophthalic acid is 0.1-3.5:100, preferably 0.5-2:100, such as 0.1:100, 0.5:100, 1.0:100, 2.0:100, 3.0:100, 3.5:100, etc.

[0047] The molar ratio of 3-nitrophthalic acid to the inorganic base is 1:2-3; more preferably 1:2-2.5, such as 1:2.0, 1:2.3, 1:2.5, 1:2.7, 1:3.0, etc.

[0048] The reducing agent can be hydrazine hydrate, and the molar ratio of the reducing agent to 3-nitrophthalic acid is 2-4:1, preferably 2.5-3.5:1, such as 2.0:1, 2.5:1, 3.0:1, 3.5:1, 4.0:1, etc.

[0049] The dehydrating agent is selected from at least one of polyphosphoric acid, concentrated sulfuric acid and phosphorus pentoxide, and can be any one or several of the above. The molar ratio of the dehydrating agent to 3-nitrophthalic acid is 20-40:1, preferably 25-35:1, such as 20:1, 25:1, 30:1, 35:1, 40:1, etc.

[0050] It should be noted that by optimizing the types and amounts of the raw materials in the reduction and cyclization processes, the reduction and cyclization are carried out in one step reaction, and there is no need to perform more additional pre-purification treatment on the process products, making the synthesis process simple and easy to operate, and the reaction conditions are milder.

[0051] In an alternative embodiment, after the reduction reaction is completed, it is mixed with the dehydrating agent, heated to reflux for 1 h-3 h, and tracked by liquid chromatography until the reaction is complete. Preferably, the reflux time is 1.5 h-2.5 h to make the reaction proceed fully.

[0052] Specifically, the reflux temperature is the atmospheric boiling point of the mixed system solvent, and the reflux time can be 1.0 h, 1.5 h, 2.0 h, 2.5 h, 3.0 h, etc.

[0053] S2. Diazotization and hydrolysis

[0054] The solid material is subjected to diazotization and hydrolysis in the presence of sodium nitrite to obtain the target product.

[0055] In the actual operation process, solid materials, water and inorganic acid are mixed, and then a sodium nitrite solution is added dropwise for reaction. The reaction temperature is controlled at 0°C - 5°C, and the reaction time is 1h - 3h. Then, the temperature is raised to 30°C - 50°C for heat preservation for 2h - 6h. Preferably, during the process of adding the sodium nitrite solution for reaction, the reaction temperature is controlled at 0°C - 3°C, the reaction time is 2h - 3h, and the heat preservation time is 3h - 5h.

[0056] Specifically, during the process of adding the sodium nitrite solution for reaction, the reaction temperature can be 0°C, 1°C, 2°C, 3°C, 4°C, 5°C, etc., and the reaction time can be 1h, 2h, 3h, etc.; then the temperature is raised for reaction, and the reaction temperature can be 30°C, 35°C, 40°C, 45°C, 50°C, etc., and the heat preservation time can be 2h, 3h, 4h, 5h, 6h, etc.

[0057] In some embodiments, the molar ratio of sodium nitrite to 3-nitrophthalic acid is 1.5 - 1.8:1, such as 1.5:1, 1.6:1, 1.7:1, 1.8:1, etc. The inorganic acid is selected from at least one of concentrated sulfuric acid and concentrated hydrochloric acid, and can be any one or several of the above. The molar ratio of the inorganic acid to 3-nitrophthalic acid is 8 - 11:1, such as 8:1, 9:1, 10:1, 11:1, etc.

[0058] S3. Separation and purification

[0059] After the heat preservation in step S2 is completed, extraction is carried out. The obtained organic phase is concentrated and dried to obtain a white crude product, and the crude product is recrystallized to obtain a white pure product.

[0060] In some embodiments, extraction is carried out by using ethyl acetate for multiple extractions, and the organic phases are combined to fully extract the target product through multiple extractions.

[0061] The number of extractions is not limited, and can be 3 times, 4 times, 5 times, 6 times, etc. The mass ratio of the amount of ethyl acetate used for each extraction to the mass of the reaction solution is 0.3 - 1:1, such as 0.3:1, 0.5:1, 0.7:1, 1.0:1, etc.

[0062] In some embodiments, the drying temperature is 70°C - 90°C, and the drying time is 6h - 10h to remove impurities on the surface of the solid. The drying temperature can be 70°C, 80°C, 90°C, etc., and the drying time can be 6h, 8h, 10h, etc.

[0063] In some embodiments, recrystallization is carried out using acetone to further improve the purity of the product.

[0064] The features and properties of the present invention are further described in detail below in conjunction with embodiments.

[0065] It should be noted that the instrument for high performance liquid chromatography (HPLC) test in the following examples is Shimadzu LC-2030 high performance liquid chromatograph, ultraviolet-visible light detector, Durashell C18 (L) chromatographic column (250×4.6 mm i.d.; particle size, 5 μm), column temperature: 25 °C, detector wavelength: 254 nm, mobile phase ratio: 0.1% trifluoroacetic acid aqueous solution - acetonitrile (30:70), mobile phase flow rate: 1 mL / min.

[0066] Example 1

[0067] This example provides a preparation method of 3-hydroxyphthalic anhydride, which includes the following steps:

[0068] (1) First, add 3-nitrophthalic acid (106 g, 0.5 mol), potassium hydroxide (83 g, 1.25 mol), solvent toluene (2.5 L), and catalyst palladium on carbon (1.06 g, purchased from Xi'an Kaili New Materials Co., Ltd., palladium on carbon, grade: KL0105001) into the reaction flask and start stirring. After stirring for 30 min, hydrazine hydrate (79 g, 1.25 mol) is slowly added dropwise at room temperature. During the dropping process, the reaction system will slowly heat up. After the dropping is completed, the reaction is carried out for 3 h at a reaction temperature of 35 °C. After the reaction is completed, polyphosphoric acid (12.5 mol) is added and the temperature is raised for reflux for 2 h. The whole process is sampled and tracked by liquid chromatography. After the reflux is completed, the raw materials have been completely converted. After the reaction is completed, the supernatant is taken and filtered, and the catalyst palladium on carbon is recovered for repeated use. The filtrate is concentrated to obtain 102 g of solid.

[0069] (2) Add the solid obtained in step (1) and deionized water (3 L) into the reaction flask, slowly add concentrated sulfuric acid (392 g, 4 mol) dropwise, and then slowly add an aqueous solution of sodium nitrite (55.2 g, 0.8 mol) for reaction. The reaction temperature is controlled at 2 °C and the reaction time is 2 h during the whole process. After the reaction is completed, the temperature is raised to 40 °C and kept warm for 4 h. The whole process is monitored by HPLC until the conversion is complete.

[0070] (3) After the insulation in step (2) is completed, the system is extracted with ethyl acetate three times, with each amount being 0.5 times the weight of the system. Then, the organic phases are combined, concentrated, and vacuum dried at 80 °C for 8 h to obtain 68.4 g of off-white crude 3-hydroxyphthalic anhydride with a purity of 98.3% and a yield of 82%. The crude product is recrystallized with acetone to obtain a white pure product (purity 99.5%).

[0071] The hydrogen spectrum of the product prepared in this example is as Figure 1As shown, 1H NMR (400 MHz, DMSO-d6) δ 11.73 (s, 1H), 7.85–7.67 (m, 1H), 7.42 (d, J = 7.2 Hz, 1H), 7.31 (d, J = 8.3 Hz, 1H).

[0072] The chromatogram of the product prepared in this example is as Figure 2 shown.

[0073] Example 2

[0074] This example provides a preparation method of 3-hydroxyphthalic anhydride, which includes the following steps:

[0075] (1) First, add 3-nitrophthalic acid (212 g, 1 mol), potassium hydroxide (165 g, 2.5 mol), solvent toluene (5 L), and catalyst palladium-carbon (3.18 g) into a reaction flask and start stirring. After stirring for 30 min, hydrazine hydrate (188 g, 3 mol) is slowly added dropwise at room temperature. During the addition process, the reaction system will slowly warm up. After the addition is complete, react for 3 h at a reaction temperature of 40 °C. After the reaction is completed, add polyphosphoric acid (30 mol) and continue to reflux for 1.5 h. Samples are taken by liquid chromatography throughout the process. After the reflux is completed, the raw materials have been completely converted. After the reaction is completed, take the supernatant and filter. The catalyst palladium-carbon is recovered for repeated use. The filtrate is concentrated to obtain 193 g of solid.

[0076] (2) Add the solid obtained in step (1) and deionized water (6 L) into a reaction flask, slowly add concentrated sulfuric acid (882 g, 9 mol) dropwise, and then slowly add an aqueous solution of sodium nitrite (110.4 g, 1.6 mol) to react. The reaction temperature is controlled at 2 °C and the reaction time is 3 h throughout the process. After the reaction is completed, raise the temperature to 30 °C and keep it warm for 4 h. The conversion is monitored by HPLC throughout the process until it is complete.

[0077] (3) After the heat preservation is completed, the system is extracted with ethyl acetate three times, with each amount being 0.6 times the weight of the system. Then, the organic phases are combined, concentrated, and vacuum dried at 80 °C for 8 h to obtain off-white crude 3-hydroxyphthalic anhydride (143.5 g, purity 97.2%), with a yield of 85%. The crude product is recrystallized from acetone to obtain a white pure product (purity 99.1%).

[0078] Example 3

[0079] This example provides a preparation method of 3-hydroxyphthalic anhydride, which includes the following steps:

[0080] (1) First, add 3-nitrophthalic acid (212 g, 1 mol), potassium hydroxide (185 g, 2.8 mol), solvent toluene (5 L), and catalyst palladium on carbon (6.36 g) into the reaction flask and start stirring. After stirring for 30 min, hydrazine hydrate (188 g, 3 mol) is slowly added dropwise at room temperature. During the addition process, the reaction system will gradually warm up. After the addition is complete, the reaction is carried out for 4 h at a reaction temperature of 40 °C. After the reaction is completed, polyphosphoric acid (30 mol) is added and the temperature is raised for reflux for 2.5 h. The whole process is monitored by taking samples with liquid chromatography. After the reflux is completed, the raw materials have been completely converted. After the reaction is completed, the supernatant is taken and filtered, and the catalyst palladium on carbon is recovered for repeated use. The filtrate is concentrated to obtain 182 g of solid.

[0081] (2) Add the solid obtained in step (1) and deionized water (6 L) into the reaction flask, slowly add concentrated sulfuric acid (882 g, 9 mol) dropwise, and then slowly add an aqueous solution of sodium nitrite (124.2 g, 1.8 mol) for reaction. The reaction temperature is controlled at 0 °C and the reaction time is 3 h during the whole process. After the reaction is completed, the temperature is raised to 50 °C and kept warm for 4 h. The whole process is monitored by HPLC until the conversion is complete.

[0082] (3) After the heat preservation is completed, the system is extracted with ethyl acetate 4 times, with each extraction amount being 1 time the weight of the system. Then, the organic phases are combined, concentrated, and vacuum dried at 80 °C for 8 h to obtain 134.5 g of off-white crude 3-hydroxyphthalic anhydride (purity 98.8%), with a yield of 81%. The crude product is recrystallized with acetone to obtain a white pure product (purity 99.75%).

[0083] Example 4

[0084] This example provides a preparation method of 3-hydroxyphthalic anhydride, which includes the following steps:

[0085] (1) First, add 3-nitrophthalic acid (1060 g, 5 mol), potassium hydroxide (989 g, 15 mol), solvent toluene (25 L), and catalyst palladium on carbon (31.8 g) into the reaction flask and start stirring. After stirring for 30 min, hydrazine hydrate (1095 g, 17.5 mol) is slowly added dropwise at room temperature. During the addition process, the reaction system will gradually warm up. After the addition is complete, the reaction is carried out for 4 h at a reaction temperature of 35 °C. After the reaction is completed, polyphosphoric acid (150 mol) is added and the temperature is raised for reflux for 2.5 h. The whole process is monitored by taking samples with liquid chromatography. After the reflux is completed, the raw materials have been completely converted. After the reaction is completed, the supernatant is taken and filtered, and the catalyst palladium on carbon is recovered for repeated use. The filtrate is concentrated to obtain 1031 g of solid.

[0086] (2) Add the solid obtained in step (1) and deionized water (30 L) to a reaction flask, slowly add concentrated sulfuric acid (3920 g, 40 mol) dropwise, and then slowly add an aqueous solution of sodium nitrite (124.2 g, 7.5 mol) for reaction. Control the reaction temperature at 0 °C during the whole process and the reaction time at 2 h. After the reaction is completed, raise the temperature to 40 °C and keep it warm for 3 h. Monitor the whole process by HPLC until the conversion is complete.

[0087] (3) After the heat preservation is completed, extract the system with ethyl acetate 4 times, with each amount being 0.5 times the weight of the system. Then combine the organic phases, concentrate them, and dry them under vacuum at 80 °C for 8 h to obtain a pale white crude product of 3-hydroxyphthalic anhydride (716.4 g, purity 98.5%), with a yield of 86%. The crude product is recrystallized from acetone to obtain a white pure product (purity 99.2%).

[0088] Comparative Example 1

[0089] This comparative example provides a method for preparing 3-hydroxyphthalic anhydride, which is only different from Example 1 in that: Raney nickel is used to catalyze the first-step reaction.

[0090] The results show that: after the first-step reaction is completed, the reaction raw materials cannot react completely, and the finally obtained product is yellowish in color (37.6 g, purity 48%), with a yield of 22%.

[0091] Comparative Example 2

[0092] This comparative example provides a method for preparing 3-hydroxyphthalic anhydride, which is only different from Example 1 in that: the temperature of the second-step reaction is 30 °C.

[0093] The results show that: during the second-step reaction, there are many impurity peaks of by-products in the liquid-phase monitoring, and the finally obtained product is yellowish green in color (44.8 g, purity 66%), with a yield of 36%.

[0094] Comparative Example 3

[0095] This comparative example provides a method for preparing 3-hydroxyphthalic anhydride, which is only different from Example 1 in that: the molar ratio of concentrated sulfuric acid to 3-nitrophthalic acid added dropwise in the second-step reaction is 3:1.

[0096] The results show that: during the second-step reaction, there are many impurity peaks of by-products in the liquid-phase monitoring, and the finally obtained product is orange-yellow in color (76.2 g, purity 42%), with a yield of 39%.

[0097] Comparative Example 4

[0098] This comparative example provides a method for preparing 3-hydroxyphthalic anhydride, which is only different from Example 1 in that: after the reduction reaction is completed, a dehydrating agent is added for reaction, and the reaction temperature is 60 °C.

[0099] The results show that: the intermediate product obtained in the first step is less, and the color of the final product is orange-yellow (24.2 g, purity 62%), and the yield is 18.3%.

[0100] The above are only the preferred embodiments of the present invention and are not intended to limit the present invention. For those skilled in the art, the present invention can have various changes and modifications. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims

1. A method for preparing 3-hydroxyphthalic anhydride, characterized in that, Including: Reduce 3-nitrophthalic acid in the presence of palladium-carbon catalyst. After the reaction is completed, react with a dehydrating agent to obtain a reaction solution. Concentrate the reaction solution to obtain a solid material. Carry out diazotization hydrolysis of the solid material in the presence of sodium nitrite to obtain the target product. The reaction route is as follows: The process for preparing the solid material includes: mixing 3-nitrophthalic acid, an inorganic base, an organic solvent and the palladium-carbon catalyst, then dropwise adding a reducing agent to react, controlling the reaction temperature at 30°C - 50°C, the reaction time at 1h - 5h. After the reaction is completed, mix with the dehydrating agent to react. After the reaction is completed, take the supernatant for solid-liquid separation to obtain a reaction solution. Concentrate the reaction solution to obtain the solid material; Mix the solid material, water and an inorganic acid, then dropwise add a sodium nitrite solution to react, control the reaction temperature at 0°C - 5°C, the reaction time at 1h - 3h, and then heat up to 30°C - 50°C for heat preservation for 2h - 6h; The molar ratio of sodium nitrite to 3-nitrophthalic acid is 1.5 - 1.8:1, and the molar ratio of the inorganic acid to 3-nitrophthalic acid is 8 - 11:

1.

2. The preparation method according to claim 1, characterized in that, The organic solvent is selected from toluene.

3. The preparation method according to claim 1, characterized in that, The mass ratio of the dosage of the palladium-carbon catalyst to the mass of 3-nitrophthalic acid is 0.1 - 3.5:

100.

4. The preparation method according to claim 3, wherein The mass ratio of the dosage of the palladium-carbon catalyst to the mass of 3-nitrophthalic acid is 0.5 - 2:

100.

5. The preparation method according to claim 1, characterized in that, The inorganic base is selected from at least one of potassium hydroxide and sodium hydroxide.

6. The preparation method according to claim 5, characterized in that, The molar ratio of 3-nitrophthalic acid to the inorganic base is 1:2 - 3.

7. The preparation method according to claim 6, characterized in that, The molar ratio of 3-nitrophthalic acid to the inorganic base is 1:2 - 2.

5.

8. The preparation method according to claim 1, wherein The reducing agent is hydrazine hydrate, and the molar ratio of the reducing agent to 3-nitrophthalic acid is 2 - 4:

1.

9. The preparation method according to claim 8, characterized in that, The molar ratio of the reducing agent to 3-nitrophthalic acid is 2.5 - 3.5:

1.

10. The preparation method according to claim 1, characterized in that, The dehydrating agent is selected from at least one of polyphosphoric acid, concentrated sulfuric acid and phosphorus pentoxide.

11. The preparation method according to claim 10, wherein The molar ratio of the dehydrating agent to 3-nitrophthalic acid is 20 - 40:

1.

12. The preparation method according to claim 11, characterized in that, The molar ratio of the dehydrating agent to 3-nitrophthalic acid is 25 - 35:

1.

13. The preparation method according to claim 10, characterized in that, After the reduction reaction is completed, mix with the dehydrating agent, heat up to reflux for 1h - 3h, and track by liquid chromatography until the reaction is complete.

14. The preparation method according to claim 13, wherein The reflux time is 1.5h - 2.5h.

15. The preparation method according to claim 1, characterized in that, During the process of dropwise adding the sodium nitrite solution to react, control the reaction temperature at 0°C - 3°C, the reaction time at 2h - 3h, and the heat preservation time at 3h - 5h.

16. The preparation method according to claim 15, wherein, The inorganic acid is selected from at least one of concentrated sulfuric acid and concentrated hydrochloric acid.

17. The preparation method according to claim 15, characterized in that, Also including: After the heat preservation is completed, carry out extraction. Concentrate and dry the obtained organic phase to obtain a crude product, and recrystallize the crude product.

18. The preparation method according to claim 17, characterized in that, The extraction is carried out by extracting multiple times with ethyl acetate, combining the organic phases. The amount of ethyl acetate used for each extraction and the mass ratio of the reaction solution is 0.3 - 1:

1.

19. The preparation method according to claim 18, characterized in that, The number of extraction times is 3 - 6 times.

20. The preparation method according to claim 19, wherein The number of extraction times is 3 - 4 times.

21. The preparation method according to claim 17, characterized in that, The drying temperature is 70°C - 90°C, and the drying time is 6h - 10h.

22. The preparation method according to claim 17, characterized in that, Recrystallize using acetone.

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