Preparation method of 4-sulfonic phthalonitrile
The conversion of 4-bromophthalic anhydride to 4-sulfonic acid phthalonitrile through a series of reaction steps solves the problem of low yield in the existing technology and improves the near-infrared absorption capacity and solubility of phthalocyanine compounds.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-12-24
- Publication Date
- 2026-04-10
AI Technical Summary
In the prior art, the yield of 4-sulfonic acid phthalonitrile is low, and it is difficult to selectively introduce substituents, resulting in insufficient near-infrared absorption capacity and solubility of phthalocyanine compounds.
The conversion of 4-bromophthalic anhydride to 4-sulfonic acid phthalonitrile is achieved through a series of steps, including reaction with formamide, reaction with ammonia, treatment with a dehydrating agent, reaction with potassium carbonate and thiol compounds, treatment with halogen elements, and reaction with hydrochloric acid solution. The temperature and time of each step are controlled to improve selectivity and yield.
A high-yield synthesis of 4-sulfonic acid phthalonitrile was achieved, improving the near-infrared absorption capacity and solubility of phthalocyanine compounds in organic solvents.
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Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to the technical field of organic synthesis, and particularly relates to a preparation method of 4-sulfonic phthalonitrile. BACKGROUND
[0002] Phthalocyanine compounds, as an important organic semiconductor, have been widely used in various functional electronic devices and are the most promising and versatile organic materials. Introducing substituents on the benzene ring of the phthalocyanine skeleton can improve near-infrared absorption, and improve solubility in various organic solvents and weather resistance, etc. Generally, substituents are introduced on the benzene ring of phthalonitrile or phthalic anhydride, and the corresponding phthalocyanine compounds are synthesized using the phthalonitrile derivative or the phthalic anhydride derivative. In the synthesis of such phthalonitrile derivative or phthalic anhydride derivative, nitrated phthalonitrile is used as a starting material, and substituents are added through diazotization of amino groups. However, in the production method using nitrated phthalonitrile as a starting material, the production steps are many, and it is not easy to introduce the desired substituents with regioselectivity, and the yield is also very low. There is also a method of converting phthalic anhydride into sulfonated phthalic anhydride by using concentrated sulfuric acid, which cannot selectively introduce the sulfone group in the concentrated sulfuric acid sulfonation step, and there are mixed isomers, which reduces the purity of the product, and the yield of the finally obtained phthalocyanine compound is also very low. In phthalocyanine compounds, when isomers are mixed, there is a problem that molecular lamination cannot be effectively performed, and in particular, the near-infrared absorption capacity cannot be improved.
[0003] In order to improve the above-mentioned properties (in particular, the near-infrared absorption capacity), the present application introduces substituents at the symmetrical position of the phthalic acid skeleton. It has been found through research that, in particular, phthalocyanine compounds obtained from 4-phthalonitrile derivatives have excellent near-infrared absorption capacity, improved solubility in various organic solvents, and weather resistance.
[0004] However, as described above, in the conventional production method, it is extremely difficult to synthesize 4-phthalonitrile derivatives, i.e., phthalonitrile derivatives having regioselective substituents. Therefore, how to improve the yield of 4-sulfonic phthalonitrile is a problem that needs to be solved urgently. SUMMARY
[0005] The present application relates to the technical field of organic synthesis, and particularly relates to a preparation method of 4-sulfonic phthalonitrile.
[0006] In order to achieve the above-mentioned application purpose, the present application provides the following technical solutions: The present application provides a preparation method of 4-sulfonic phthalonitrile, comprising the following steps: (1) performing a first reaction of 4-bromophthalic anhydride and formamide to obtain 4-bromophthalimide; (2) performing a second reaction of 4-bromophthalimide and ammonia water to obtain 4-bromophthalic amide; (3) performing a third reaction of a dehydrating agent, 4-bromophthalic amide mixed in a solvent to obtain 4-bromophthalonitrile; (4) performing a fourth reaction of 4-bromophthalonitrile, potassium carbonate and a thiol group compound mixed in a solvent to obtain a 4-benzylthiophthalonitrile derivative; the thiol group compound has a structural formula of wherein R is hydrogen or C1-C4 alkyl; the 4-benzylthiophthalonitrile derivative has a structural formula of wherein R is hydrogen or C1-C4 alkyl.
[0007] (5) performing a fifth reaction of the 4-benzylthiophthalonitrile derivative and acetic acid solution mixed with addition of a halogen element to obtain 4-halosulfonylphthalonitrile; (6) performing a sixth reaction of 4-halosulfonylphthalonitrile mixed with hydrochloric acid solution to obtain 4-sulfonic acid phthalonitrile.
[0008] Preferably, in step (1), the molar ratio of 4-bromophthalic anhydride to formamide is 0.1-0.5:8-12; the temperature of the first reaction is 90-160°C, and the time of the first reaction is 2-6h.
[0009] Preferably, in step (2), the molar ratio of 4-bromophthalimide to ammonia water is 0.2-0.5 mol:300-500 mL; the temperature of the second reaction is 20-30°C, and the time of the second reaction is 6-10h.
[0010] Preferably, in step (3), the molar ratio of the dehydrating agent to 4-bromophthalimide is 0.6-0.9:0.1-0.5; the dehydrating agent is thionyl chloride; the temperature of the third reaction is 20-30°C, and the time of the third reaction is 1-3h.
[0011] Preferably, in step (4), the molar ratio of 4-bromophthalonitrile, potassium carbonate and the thiol group compound is 0.1-0.3:0.2-0.6:0.1-0.3; the temperature of the fourth reaction is 70-80°C, and the time of the fourth reaction is 1-4h.
[0012] As preferred, in step (5), the molar volume ratio of the 4-benzylthiophthalonitrile derivative and the aqueous acetic acid solution is 0.05-0.3 mol: 200-300 mL; the molar ratio of the 4-benzylthiophthalonitrile derivative and the halogen element is 0.05-0.3: 0.05-0.4; and the halogen element is liquid bromine or chlorine.
[0013] As preferred, in step (5), the temperature of the fifth reaction is -10-60°C, and the time of the fifth reaction is 0.5-5 h.
[0014] As preferred, in step (6), the molar volume ratio of the 4-chlorosulfonylphthalonitrile and the aqueous hydrochloric acid solution is 0.1-0.3 mol: 40-60 mL.
[0015] As preferred, in step (6), the temperature of the sixth reaction is 5-30°C, and the time of the sixth reaction is 1-3 h.
[0016] Advantages of the present application: The present application provides a method for preparing 4-sulfophthalonitrile with high yield, and the method for preparing 4-sulfophthalonitrile can be applied to the synthesis of, for example, 3-sulfophthalonitrile, phthalonitrile derivatives with substituents at multiple positions, and the like. DETAILED DESCRIPTION
[0017] The present application provides a method for preparing 4-sulfophthalonitrile, comprising the following steps: (1) performing a first reaction of 4-bromophthalic anhydride and formamide to obtain 4-bromophthalimide; (2) performing a second reaction of 4-bromophthalimide and aqueous ammonia to obtain 4-bromophthalic acid amide; (3) performing a third reaction of a dehydrating agent and 4-bromophthalic acid amide in a solvent to obtain 4-bromophthalonitrile; (4) performing a fourth reaction of 4-bromophthalonitrile, potassium carbonate, and a thiol compound in a solvent to obtain a 4-benzylthiophthalonitrile derivative; The structure of the thiol compound is wherein R is hydrogen or C1-C4 alkyl. The structure of the 4-benzylthiophthalonitrile derivative is wherein R is hydrogen or C1-C4 alkyl.
[0018] (5) performing a fifth reaction of the 4-benzylthiophthalonitrile derivative and an acetic acid solution by adding a halogen element to obtain 4-halosulfonylphthalonitrile; (6) the sixth reaction is carried out after mixing 4-halosulfonyl phthalonitrile and hydrochloric acid solution, and 4-sulfonic acid phthalonitrile is obtained.
[0019] In the application, 4-sulfonic acid phthalonitrile has the structure as shown in (I): (I).
[0020] In the application, the synthesis route of 4-bromophthalonitrile is as follows: ; The synthesis route of 4-sulfonic acid phthalonitrile is as follows:
[0021] In the application, in step (1), the molar ratio of 4-bromophthalic anhydride to formamide is 0.1-0.5:8-12, preferably 0.2-0.4:9-11, and further preferably 0.3-0.4:10; the temperature of the first reaction is 90-160℃, preferably 100-150℃, and further preferably 120-130℃; and the time of the first reaction is 2-6h, and specifically can be 3h, 4h, or 5h.
[0022] In the application, in step (2), the molar ratio of 4-bromophthalic acid to ammonia water is 0.2-0.5mol:300-500mL, preferably 0.3-0.4mol:350-450mL, and further preferably 0.34-0.38mol:400mL; the temperature of the second reaction is 20-30℃, preferably 22-28℃, and further preferably 25℃; and the time of the second reaction is 6-10h, and specifically can be 7h, 8h, or 9h.
[0023] In the application, the concentration of the ammonia water is 28%.
[0024] In the application, in step (3), the molar ratio of the dehydrating agent to 4-bromophthalic acid is 0.6-0.9:0.1-0.5, preferably 0.7-0.8:0.2-0.4, and further preferably 0.73-0.77:0.31-0.35; the dehydrating agent is thionyl chloride; the temperature of the third reaction is 20-30℃, preferably 22-28℃, and further preferably 25℃; and the time of the third reaction is 1-3h, and specifically can be 1h, 2h, or 3h.
[0025] In the present application, in step (4), the molar ratio of the 4-bromophthalonitrile, potassium carbonate and thiol compound is 0.1-0.3:0.2-0.6:0.1-0.3, preferably 0.16-0.25:0.32-0.50:0.16-0.25; the temperature of the fourth reaction is 70-80℃, preferably 72-78℃, further preferably 75℃; the time of the fourth reaction is 1-4h, specifically 1h, 2h, 3h, 4h.
[0026] In the present application, in step (5), the molar volume ratio of the 4-benzylthiophthalonitrile derivative and acetic acid solution is 0.05-0.3mol:200-300mL, preferably 0.1-0.2mol:250mL; the molar ratio of the 4-benzylthiophthalonitrile derivative and halogen element is 0.05-0.3:0.05-0.4, preferably 0.1-0.2:0.32-0.35; the halogen element is liquid bromine or chlorine.
[0027] In the present application, the acetic acid solution is mixed by acetic acid and water or mixed by acetic acid, water and organic solvent, wherein the organic solvent comprises methanol, ethanol, chloroform or dichloromethane.
[0028] In the present application, in step (5), the temperature of the fifth reaction is -10-60℃, specifically -10℃, -5℃, 0℃, 10℃, 20℃; the time of the fifth reaction is 0.5-5h, specifically 1h, 2h, 3h, 4h.
[0029] In the present application, in step (6), the molar volume ratio of the 4-halosulfonylphthalonitrile and hydrochloric acid aqueous solution is 0.1-0.3mol:40-60mL, preferably 0.15-0.25mol:45-55mL, further preferably 0.18-0.20mol:50mL.
[0030] In the present application, the concentration of the hydrochloric acid aqueous solution is 0.01M.
[0031] In the present application, in step (6), the temperature of the sixth reaction is 5-30℃, specifically 10℃, 20℃, 25℃, the time of the sixth reaction is 1-3h, preferably 2h.
[0032] The technical solutions provided by the present application are described in detail below in combination with examples, but they should not be understood as limiting the scope of protection of the present application.
[0033] Example 1
[0034] 90.8 g (0.4 mol) of 4-bromophthalic anhydride was added to 450 g (10 mol) of formamide. The mixture was stirred at 125 °C for 3 h. After the reaction was complete, the reaction solution was cooled to room temperature, and 400 mL of methanol was added to the reaction solution. The precipitate was separated by filtration, washed with a small amount of methanol, and air-dried overnight to obtain 76.9 g (0.34 mol) of white 4-bromophthalimide crystals, with a yield of 85%. 76.9 g (0.34 mol) of 4-bromophthalimide was added in portions to 400 mL of 28% ammonia solution. The system temperature was maintained at -5 °C during the addition process. The resulting mixture was stirred at 25 °C for 8 h to allow the reaction to proceed. After the reaction was completed, the precipitate was obtained by filtration. The precipitate was washed successively with distilled water and methanol, and finally dried with an infrared lamp to obtain 74.5 g (0.31 mol) of 4-bromophthalimide, with a yield of 91%. 91.2 g (0.77 mol) of thionyl chloride was added dropwise to 360 mL of N,N-dimethylformamide (DMF). The temperature of the mixture was controlled at 5 °C and maintained for 30 min, then stirred for 1 h. Next, 74.5 g (0.31 mol) of 4-bromophthalamide was added in portions to the mixture while maintaining the temperature at 0 °C. After the addition was complete, the temperature was raised to 10 °C and stirred for 1 h. After stirring, the temperature was raised to 25 °C and stirred for another 2 h for dehydration. After the reaction was complete, the solution was poured into ice water, the precipitate was filtered to obtain crystals, which were washed with distilled water, air-dried at room temperature, and finally recrystallized in toluene and n-hexane (volume ratio of n-hexane to toluene 3:1) to obtain 60.0 g (0.29 mol) of white 4-bromophthalonitrile crystals, with a yield of 94%. 33.5 g (0.16 mol) of 4-bromophthalonitrile was dissolved in 325 mL of N,N-dimethylformamide (DMF), and 44.8 g (0.32 mol) of potassium carbonate and 20.1 g (0.16 mol) of benzylthiol were added. The mixture was heated to 75 °C and stirred for 3 h. Then it was cooled to room temperature, and the reaction solution was poured into ice water. The precipitate was separated by filtration, washed with distilled water, dried, and finally recrystallized from toluene to give 34.3 g (0.14 mol) of 4-benzylthiophthalonitrile, with a yield of 88%.
[0035] 25.0 g (0.10 mol) of 4-benzylthiophthalonitrile was added to 250 mL of an aqueous acetic acid solution (210 mL of acetic acid and 40 mL of water). The mixture was cooled to 5 °C in an ice-water bath and maintained at that temperature. 22.5 g (0.32 mol) of chlorine gas was introduced into the solution over 1 hour. After the addition was complete, the mixture was stirred for 1 hour to allow the reaction to proceed. After the reaction was completed, the precipitate was separated by filtration, washed successively with water and isopropanol, and finally dried in a forced-air drying oven at 40 °C to obtain 16.6 g (0.073 mol) of white 4-chlorosulfonylphthalonitrile crystals, with a yield of 73%. 4.1 g (18 mmol) of 4-chlorosulfonyl phthalonitrile was added to 50 mL of 0.01 M hydrochloric acid aqueous solution and stirred at atmospheric pressure at 10 °C for 2 h. After the reaction was completed, the target product was extracted with dichloromethane and rotary distilled to obtain 2.6 g (0.0125 mol) of 4-sulfonyl phthalonitrile white solid, with a yield of 69%.
[0036] Example 2
[0037] The difference from Example 1 is that 22.5 g (0.32 mol) of chlorine gas was introduced into the solution within 4 hours, while all other conditions were the same, resulting in 14.0 g (0.062 mol) of white 4-chlorosulfonyl phthalonitrile crystals with a yield of 62%.
[0038] Example 3
[0039] The difference from Example 1 is that the amount of chlorine gas introduced is different. The amount of chlorine gas introduced is 7.5g (0.11mol), and all other conditions are the same. 14.8g (0.065mol) of white 4-chlorosulfonyl phthalonitrile crystals were obtained, with a yield of 65%.
[0040] Example 4
[0041] The difference from Example 1 is that the aqueous solution of acetic acid in Example 1 was replaced with a mixed solution of chloroform and water containing acetic acid, wherein 210 mL of acetic acid + 32 mL of chloroform + 8 mL of water, and all other conditions were the same, yielding 15.9 g (0.07 mol) of white crystals of 4-chlorosulfonyl phthalonitrile, with a yield of 70%.
[0042] Example 5
[0043] The difference from Example 1 is that 4-bromosulfonyl phthalonitrile was prepared. The preparation process was as follows: 25.0 g (0.10 mol) of 4-benzylthiophthalonitrile was added to 250 mL of acetic acid aqueous solution (210 mL of acetic acid + 40 mL of water), and the mixture was cooled to 5 °C in an ice-water bath and maintained at this temperature. 48 g (0.30 mol) of liquid bromine was added dropwise to the above mixed solution. After the addition was complete, the mixture was stirred for 1 h to carry out the reaction. After the reaction was completed, the precipitate obtained by filtration was washed with water and isopropanol in sequence, and finally dried in a forced-air drying oven at 40 °C to obtain 18.4 g (0.068 mol) of white crystals of 4-bromosulfonyl phthalonitrile, with a yield of 68%. Then, 4-sulfonic acid phthalonitrile was prepared using 4-bromosulfonyl phthalonitrile under the same conditions.
[0044] Example 6
[0045] The difference from Example 1 is that 4-methylbenzylthiol was used instead of benzylthiol to prepare 31.68 g (0.12 mol) of 4-(4-methylbenzylthio)phthalonitrile with a yield of 75%. Then, 4-chlorosulfonyl phthalonitrile was prepared using 4-(4-methylbenzylthio)phthalonitrile under the same conditions.
[0046] Comparative Example 1
[0047] 25.0 g (0.10 mol) of 4-phenylthiophthalonitrile was added to 250 mL of aqueous acetic acid solution (210 mL acetic acid + 40 mL water), and the mixture was cooled to 5 °C in an ice-water bath and maintained at that temperature. 22.5 g (0.32 mol) of chlorine gas was introduced into the solution over 1 hour. After the addition was complete, the mixture was stirred for 1 hour to allow the reaction to proceed. After the reaction was completed, the precipitate was separated by filtration, washed successively with water and isopropanol, and finally dried in a forced-air drying oven at 40 °C to obtain 3.4 g (0.015 mol) of white 4-chlorosulfonyl phthalonitrile crystals, with a yield of 15%.
[0048] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.
Claims
1. A method for preparing 4-sulfonic acid phthalonitrile, characterized in that, Includes the following steps: (1) 4-Bromophthalic anhydride and formamide are reacted in the first reaction to obtain 4-bromophthalimide; (2) 4-bromophthalimide and ammonia water are reacted in a second reaction to obtain 4-bromophthalamide; (3) The dehydrating agent and 4-bromophthalamide are mixed in a solvent to carry out the third reaction to obtain 4-bromophthalonitrile; (4) 4-Bromophthalonitrile, potassium carbonate and thiol compound were mixed in a solvent to carry out the fourth reaction to obtain 4-benzylthiophthalonitrile derivative; The structural formula of the thiol-based compound is as follows: , where R is hydrogen or a C1~C4 alkyl group; The structural formula of the 4-benzylthiophthalonitrile derivative is as follows: , where R is hydrogen or a C1~C4 alkyl group; (5) Mix the 4-benzylthiophthalonitrile derivative with acetic acid solution, add halogen element to carry out the fifth reaction, and obtain 4-halosulfonylphthalonitrile; (6) Mix 4-halosulfonyl phthalonitrile with hydrochloric acid solution and carry out the sixth reaction to obtain 4-sulfonyl phthalonitrile.
2. The method for preparing 4-sulfonic acid phthalonitrile according to claim 1, characterized in that, In step (1), the molar ratio of 4-bromophthalic anhydride to formamide is 0.1~0.5:8~12; the temperature of the first reaction is 90~160℃, and the reaction time is 2~6h.
3. The method for preparing 4-sulfonic acid phthalonitrile according to claim 1 or 2, characterized in that, In step (2), the molar ratio of 4-bromophthalimide to ammonia is 0.2~0.5mol:300~500mL; the temperature of the second reaction is 20~30℃, and the reaction time is 6~10h.
4. The method for preparing 4-sulfonic acid phthalonitrile according to claim 3, characterized in that, In step (3), the molar ratio of the dehydrating agent to 4-bromophthalamide is 0.6~0.9:0.1~0.5; the dehydrating agent is thionyl chloride; the temperature of the third reaction is 20~30℃, and the time of the third reaction is 1~3h.
5. The method for preparing 4-sulfonic acid phthalonitrile according to claim 1, 2, or 4, characterized in that, In step (4), the molar ratio of 4-bromophthalonitrile, potassium carbonate and thiol compound is 0.1~0.3:0.2~0.6:0.1~0.3; the temperature of the fourth reaction is 70~80℃ and the time of the fourth reaction is 1~4h.
6. The method for preparing 4-sulfonic acid phthalonitrile according to claim 5, characterized in that, In step (5), the molar volume ratio of the 4-benzylthiophthalonitrile derivative to the acetic acid solution is 0.05~0.3mol:200~300mL; the molar ratio of the 4-benzylthiophthalonitrile derivative to the halogen is 0.05~0.3:0.05~0.4; and the halogen is liquid bromine or chlorine gas.
7. The method for preparing 4-sulfonic acid phthalonitrile according to claim 4 or 6, characterized in that, In step (5), the temperature of the fifth reaction is -10~60℃, and the time of the fifth reaction is 0.5~5h.
8. The method for preparing 4-sulfonic acid phthalonitrile according to claim 7, characterized in that, In step (6), the molar volume ratio of the 4-chlorosulfonyl phthalonitrile and the hydrochloric acid aqueous solution is 0.1~0.3mol:40~60mL.
9. The method for preparing 4-sulfonic acid phthalonitrile according to claim 7, characterized in that, In step (6), the temperature of the sixth reaction is 5~30℃ and the time of the sixth reaction is 1~3h.