A method for synthesizing 2-hydroxy-6-naphthoic acid

Abstract

The application discloses a synthesis method of 2-hydroxy-6-naphthalene carboxylic acid, and aims to solve the problems of low conversion rate of naphthol, harsh reaction conditions such as high temperature and high pressure and the like in the prior synthesis method of 2-hydroxy-6-naphthalene carboxylic acid. The synthesis method comprises the following steps: firstly, mixing beta-naphthol, isopropyl chloride, a first catalyst and an organic solvent to obtain 2-isopropoxy naphthalene; secondly, dissolving aluminum chloride in an organic solvent, adding chloromethane to obtain an alkylating agent; adding the alkylating agent into a 2-isopropoxy naphthalene solution to react at-10~0 DEG C to obtain an organic phase; thirdly, adding a second catalyst into the organic phase, and then introducing chlorine to carry out a photocatalytic reaction to obtain a reaction liquid; and fourthly, adding water into the reaction liquid, and heating to react to obtain a product. The beta-naphthol is used as a starting material, and 2-hydroxy-6-naphthalene carboxylic acid is synthesized through the processes of hydroxyl protection, methylation, photo-reaction chlorination and hydrolysis, the conversion rate is greater than 99%, and the reaction condition is mild.

Description

Technical Field

[0001] This invention relates to a method for preparing 2-hydroxy-6-naphthoic acid. Background Technology

[0002] 2-Hydroxy-6-naphthoic acid is an important organic intermediate in pharmaceuticals, organic pigments, and liquid crystal materials. In particular, liquid crystal polymers produced using 2-hydroxy-6-naphthoic acid as the main raw material have rigid rod-like molecular chains, combining liquid flowability with crystal anisotropy. They possess self-reinforcing properties, excellent heat resistance, and low melt viscosity, making them widely used in the liquid crystal materials industry. Currently, with the widespread use of liquid crystal polymers across various industries, the global annual demand for liquid crystal polymers has maintained a double-digit growth rate, with even higher growth rates in Asia, reaching 30%. This high growth rate is expected to continue for the next decade, thus the demand for 2-hydroxy-6-naphthoic acid will also continue to grow rapidly.

[0003] Domestic and foreign chemical companies and researchers have explored the synthesis process of 2-hydroxy-6-naphthoic acid, which can be divided into two routes: (1) Early international patents such as EP0053824A1, EP0254596A2, US5312976A, and US5532406A adopted the Kolbe-Schmitt reaction route. After β-naphthol forms a salt with alkali, it reacts with carbon dioxide under high temperature and pressure, and then is purified by recrystallization to obtain a high-purity product, which is also the production process of most companies at present; domestic patents such as CN118063306A, CN114057566A, CN103360242A, CN87105505A, and CN115536515A have achieved industrial production by optimizing additives, auxiliaries, process parameters, etc., and improved the quality of the product to meet the requirements of polymerization. However, this process has disadvantages such as a naphthol conversion rate of less than 50% and the easy generation of tar at high temperature, which affects the product quality.

[0004] (2) In addition, patents EP0625498A1 and US5643494A use carbon monoxide and alkali metal carbonates to carry out the carboxylation reaction of naphthol salts, thereby improving the conversion rate of naphthol. This process route involves harsh reaction conditions such as high temperature and high pressure, and there are no reports of large-scale production. Summary of the Invention

[0005] The purpose of this invention is to solve the problems of low naphthol conversion rate and the need for harsh reaction conditions such as high temperature and high pressure in the existing synthesis methods of 2-hydroxy-6-naphthoic acid, and to provide a synthesis method of 2-hydroxy-6-naphthoic acid.

[0006] The method for synthesizing 2-hydroxy-6-naphthoic acid of the present invention is carried out according to the following steps:

[0007] Step 1: Mix β-naphthol, isopropyl chloride, the first catalyst, and an organic solvent, and react at a temperature of 50-80°C to obtain 2-isopropoxynaphthalene;

[0008] Step 2: Dissolve aluminum chloride in an organic solvent, add chloromethane, and keep warm at -10~0℃ to obtain an alkylating agent; prepare a 2-isopropoxynaphthalene solution, add the alkylating agent to the 2-isopropoxynaphthalene solution at -10~0℃ to carry out the reaction, add ice water after the reaction is completed, and separate to obtain the organic phase;

[0009] Step 3: Add the organic phase obtained in Step 2 into the photoreactor, add the second catalyst into the organic phase, and then introduce chlorine gas. The reaction is carried out by ultraviolet light to obtain the reaction solution.

[0010] Step 4: Add water to the reaction solution in an autoclave, and react at a temperature of 85~150℃ under nitrogen-sealed conditions. The crude reaction product obtained by filtration is then recrystallized to obtain 2-hydroxy-6-naphthoic acid.

[0011] The first catalyst mentioned in step one is sodium hydride, triethylamine, potassium carbonate, sodium carbonate, sodium methoxide, or sodium ethoxide; the second catalyst is azobisisobutyronitrile, azobisisoheptanenitrile, or benzoyl peroxide.

[0012] This invention provides a method for synthesizing 2-hydroxy-6-naphthoic acid. Compared with the Kolbe-Schmitt reaction, which generally has a raw material conversion rate of ≤50% and is prone to tar side reactions due to high temperature and high pressure, this invention develops a novel synthetic route that synthesizes 2-hydroxy-6-naphthoic acid by hydroxyl protection, methylation, photo-chlorination, and hydrolysis of β-naphthol. The raw material conversion rate is >99%, and the reaction conditions are mild and easy to control. Attached Figure Description

[0013] Figure 1 NMR of 2-hydroxy-6-naphthoic acid obtained in Example 1 1 H spectrum;

[0014] Figure 2 NMR of 2-hydroxy-6-naphthoic acid obtained in Example 1 13 C-spectrum. Detailed Implementation

[0015] Specific Implementation Method 1: The synthesis method of 2-hydroxy-6-naphthoic acid in this implementation method is carried out according to the following steps:

[0016] Step 1: Mix β-naphthol, isopropyl chloride, the first catalyst, and an organic solvent, and react at a temperature of 50-80°C to obtain 2-isopropoxynaphthalene;

[0017] Step 2: Dissolve aluminum chloride in an organic solvent, add chloromethane, and keep warm at -10~0℃ to obtain an alkylating agent; prepare a 2-isopropoxynaphthalene solution, add the alkylating agent to the 2-isopropoxynaphthalene solution at -10~0℃ to carry out the reaction, add ice water after the reaction is completed, and separate to obtain the organic phase;

[0018] Step 3: Add the organic phase obtained in Step 2 into the photoreactor, add the second catalyst into the organic phase, and then introduce chlorine gas. The reaction is carried out by ultraviolet light to obtain the reaction solution.

[0019] Step 4: Add water to the reaction solution in an autoclave, and react at a temperature of 85~150℃ under nitrogen-sealed conditions. The crude reaction product obtained by filtration is then recrystallized to obtain 2-hydroxy-6-naphthoic acid.

[0020] The first catalyst mentioned in step one is sodium hydride, triethylamine, potassium carbonate, sodium carbonate, sodium methoxide, or sodium ethoxide; the second catalyst is azobisisobutyronitrile, azobisisoheptanenitrile, or benzoyl peroxide.

[0021] The reaction formula for synthesizing 2-hydroxy-6-naphthoic acid in this embodiment is as follows:

[0022] .

[0023] This embodiment employs a novel synthetic route and introduces a green photochemical method for the concise and efficient synthesis of 2-hydroxy-6-naphthoic acid. Compared with traditional processes, it demonstrates the value of green chemistry and provides a new direction for process development in industrial production.

[0024] Specific Implementation Method Two: This implementation method differs from Specific Implementation Method One in that the organic solvent used is chlorobenzene, dichlorobenzene, dichloroethane, tetrachloroethylene, or dichloromethane.

[0025] Specific Implementation Method 3: This implementation method differs from Specific Implementation Method 1 or 2 in that the molar ratio of β-naphthol, isopropyl chloride and the first catalyst in step 1 is 1:(1.05~1.2):(2.5~5).

[0026] Specific Implementation Method Four: This implementation method differs from Specific Implementation Methods One to Three in that the mass ratio of β-naphthol to organic solvent in step one is 1:(5~15).

[0027] Specific Implementation Method 5: This implementation method differs from Specific Implementation Methods 1 to 4 in that the reaction time in step 1 is 3 to 6 hours at a temperature of 50 to 80°C.

[0028] Specific Implementation Method Six: This implementation method differs from Specific Implementation Methods One to Five in that in step two, 2-isopropoxynaphthalene is dissolved in an organic solvent to prepare a 2-isopropoxynaphthalene solution, wherein the mass ratio of 2-isopropoxynaphthalene to the organic solvent is 1: (5~15).

[0029] Specific Implementation Method Seven: This implementation method differs from Specific Implementation Methods One to Six in that the molar ratio of 2-isopropoxynaphthalene, aluminum chloride, and chloromethane in step two is 1: (2.5~3.5): (1.05~1.5).

[0030] Specific Implementation Method Eight: This implementation method differs from one of the specific implementation methods one to seven in that in step two, an alkylating agent is added at -10~0℃ and the reaction is carried out for 2~4 hours.

[0031] Specific Implementation Method Nine: This implementation method differs from Specific Implementation Methods One to Eight in that the reaction time by irradiation with ultraviolet light in step three is 3 to 8 hours.

[0032] Specific Implementation Method 10: This implementation method differs from Specific Implementation Methods 1 to 9 in that the reaction time in step 4 is 3 to 8 hours at a temperature of 85 to 150°C under nitrogen-sealed conditions.

[0033] Specific Implementation Method Eleven: This implementation method differs from Specific Implementation Methods One through Ten in that the molar ratio of 2-isopropoxynaphthalene to water in step four is 1:6~12.

[0034] Specific Implementation Method Twelve: This implementation method differs from Specific Implementation Methods One to Eleven in that the crude product in step four is recrystallized using a solvent, which is one or a mixture of water, ethanol, ethylene glycol, propylene glycol, glycerol, and tert-butanol.

[0035] In this embodiment, the mass ratio of the solvent to 2-isopropoxynaphthalene is 10~20:1.

[0036] Example 1: The synthesis method of 2-hydroxy-6-naphthoic acid in this example is carried out according to the following steps:

[0037] Step 1: In a reaction vessel, 10 g of β-naphthol, 6.5 g of isopropyl chloride, 29 g of potassium carbonate, and 120 g of dichlorobenzene were mixed and reacted at 80°C for 4 hours. After the reaction was completed, the mixture was washed with water and the solvent was evaporated to obtain 12.9 g of 2-isopropoxynaphthalene, with a naphthol conversion rate >99%.

[0038] Step 2: Dissolve 27 g of aluminum chloride in 60 g of dichlorobenzene, add 8 g of chloromethane, and keep warm at -10 °C to obtain an alkylating agent; dissolve 12.9 g of 2-isopropoxynaphthalene obtained in Step 1 in 60 g of dichlorobenzene, and then add the alkylating agent in batches at -10 °C and react for 4 hours. After the reaction is completed, add ice water and separate to obtain the organic phase;

[0039] Step 3: Add the organic phase obtained in Step 2 into the photoreactor, add 0.08 g of benzoyl peroxide, keep the temperature at 10°C, introduce chlorine gas into the organic phase through a pressure reducer, and irradiate the reaction with a 200W ultraviolet lamp for 8 hours to obtain the reaction solution.

[0040] Step 4: Add 12 grams of water to the reaction solution in the autoclave, replace with nitrogen, seal and heat to 120°C for 5 hours. The crude product obtained by filtration is recrystallized in a water / ethylene glycol system to obtain 2-hydroxy-6-naphthoic acid with a purity of 99.5%.

[0041] The overall yield of the synthesis of 2-hydroxy-6-naphthoic acid in this embodiment was 72%. (NMR) 1 H spectrum as shown Figure 1 As shown, 1 HNMR (400 MHz, DMSO-d6): δ 12.82 (s, 1H), 10.15 (s, 1H), 8.48 (s, 1H), 7.96 (d, J = 8.7 Hz, 1H), 7.87 (d, J = 8.6 Hz, 1H), 7.76 (d, J = 8.6 Hz, 1H), 7.21– 7.14 (m, 2H).

[0042] MRI 13 C spectrum as shown Figure 2 As shown, 13 C NMR (101 MHz, DMSO-d6): δ 168.16, 158.04,137.47, 131.65, 131.07, 127.16, 126.71, 126.01, 125.30, 119.98, 109.19.

[0043] Example 2: The synthesis method of 2-hydroxy-6-naphthoic acid in this example is carried out according to the following steps:

[0044] Step 1: In a reaction vessel, 13 g of β-naphthol, 8.5 g of isopropyl chloride, 21 g of sodium ethoxide, and 150 g of tetrachloroethylene were mixed and reacted at 65°C for 3 hours. After the reaction was completed, the mixture was washed with water and the solvent was evaporated to obtain 16.6 g of 2-isopropoxynaphthalene, with a naphthol conversion rate >99%.

[0045] Step 2: Dissolve 42 g of aluminum chloride in 80 g of tetrachloroethylene, add 11 g of chloromethane, and keep warm at 0 °C to obtain an alkylating agent; dissolve 16.6 g of bio-2-isopropoxynaphthalene obtained in Step 1 in 60 g of dichlorobenzene, add the alkylating agent in batches at 0 °C and react for 4 hours. After the reaction is complete, add ice water and separate to obtain the organic phase.

[0046] Step 3: Add the organic phase obtained in Step 2 into the photoreactor, add 0.6 g of benzoyl peroxide, keep the temperature at 10°C, introduce chlorine gas into the organic phase through a pressure reducer, and irradiate the reaction with a 400W ultraviolet lamp for 6 hours to obtain the reaction solution.

[0047] Step 4: Add 18 grams of water to the reaction solution in the autoclave, purge with nitrogen, seal and heat to 150°C for 3 hours. The crude product obtained by filtration is recrystallized in a water / propylene glycol system to obtain 2-hydroxy-6-naphthoic acid with a purity of 99.7%.

[0048] In this example, the overall yield of 2-hydroxy-6-naphthoic acid was 86%.

Claims

1. A method for synthesizing 2-hydroxy-6-naphthoic acid, characterized in that... The synthesis of 2-hydroxy-6-naphthoic acid is carried out according to the following steps: Step 1: Mix β-naphthol, isopropyl chloride, the first catalyst, and an organic solvent, and react at a temperature of 50-80°C to obtain 2-isopropoxynaphthalene; Step 2: Dissolve aluminum chloride in an organic solvent, add chloromethane, and keep warm at -10~0℃ to obtain an alkylating agent; prepare a 2-isopropoxynaphthalene solution, add the alkylating agent to the 2-isopropoxynaphthalene solution at -10~0℃ to carry out the reaction, add ice water after the reaction is completed, and separate to obtain the organic phase; Step 3: Add the organic phase obtained in Step 2 into the photoreactor, add the second catalyst into the organic phase, and then introduce chlorine gas. The reaction is carried out by ultraviolet light to obtain the reaction solution. Step 4: Add water to the reaction solution in an autoclave, and react at a temperature of 85~150℃ under nitrogen-sealed conditions. The crude reaction product obtained by filtration is then recrystallized to obtain 2-hydroxy-6-naphthoic acid. The first catalyst mentioned in step one is sodium hydride, triethylamine, potassium carbonate, sodium carbonate, sodium methoxide, or sodium ethoxide; the second catalyst is azobisisobutyronitrile, azobisisoheptanenitrile, or benzoyl peroxide.

2. The method for synthesizing 2-hydroxy-6-naphthoic acid according to claim 1, characterized in that... The organic solvent is chlorobenzene, dichlorobenzene, dichloroethane, tetrachloroethylene, or dichloromethane.

3. The method for synthesizing 2-hydroxy-6-naphthoic acid according to claim 1, characterized in that... In step one, the molar ratio of β-naphthol, isopropyl chloride and the first catalyst is 1:(1.05~1.2):(2.5~5).

4. The method for synthesizing 2-hydroxy-6-naphthoic acid according to claim 1, characterized in that... In step one, the mass ratio of β-naphthol to organic solvent is 1:(5~15).

5. The method for synthesizing 2-hydroxy-6-naphthoic acid according to claim 1, characterized in that... In step one, the reaction time is 3 to 6 hours at a temperature of 50 to 80°C.

6. The method for synthesizing 2-hydroxy-6-naphthoic acid according to claim 1, characterized in that... In step two, the molar ratio of 2-isopropoxynaphthalene, aluminum chloride, and chloromethane is 1:(2.5~3.5):(1.05~1.5).

7. The method for synthesizing 2-hydroxy-6-naphthoic acid according to claim 1, characterized in that... In step two, an alkylating agent is added at -10 to 0°C and the reaction is carried out for 2 to 4 hours.

8. The method for synthesizing 2-hydroxy-6-naphthoic acid according to claim 1, characterized in that... In step three, the reaction time is 3 to 8 hours under ultraviolet light.

9. The method for synthesizing 2-hydroxy-6-naphthoic acid according to claim 1, characterized in that... In step four, the reaction time is 3 to 8 hours at a temperature of 85 to 150°C under nitrogen-sealed conditions.

10. The method for synthesizing 2-hydroxy-6-naphthoic acid according to claim 1, characterized in that... In step four, the crude product is recrystallized using a solvent, which is one or a mixture of water, ethanol, ethylene glycol, propylene glycol, glycerol, and tert-butanol.

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