A method for preparing 2,2-bis(3-amino-4-hydroxyphenyl)hexafluoropropane
By using the dehydration condensation of hexafluoroacetone trihydrate with salicylamide and the Hoffmann degradation reaction, the problems of expensive raw materials and dangerous reactions in the existing technology have been solved, and the preparation of 2,2-bis(3-amino-4-hydroxyphenyl)hexafluoropropane with high yield and low cost has been achieved, which is suitable for industrial production.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- CHINATECH (TIANJIN) CHEM CO LTD
- Filing Date
- 2023-12-22
- Publication Date
- 2026-06-02
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Figure SMS_1 
Figure SMS_2 
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Abstract
Description
Technical Field
[0001] This invention belongs to the field of organic chemical synthesis technology, and in particular relates to a method for preparing 2,2-bis(3-amino-4-hydroxyphenyl)hexafluoropropane. Background Technology
[0002] Fluorinated polyimide (FPI) is a rigid polymer with a highly regular chemical structure containing an imide ring in its main chain. It is a polymeric material obtained by melt polycondensation or solution polycondensation of fluorinated dianhydrides and fluorinated diamines to produce fluorinated polyamic acid (FPAA), followed by imidization. It possesses advantages such as corrosion resistance, radiation resistance, high and low temperature resistance, superior mechanical properties, and good adhesion, and is widely used in electronics, OLEDs, aerospace, flame retardancy, and precision machinery, becoming an irreplaceable high-performance polymeric material with high development value. 2,2-Bis(3-amino-4-hydroxyphenyl)hexafluoropropane (6FAP), as a novel monomer for fluorinated polyimide materials, can be used as a monomer for preparing polyimide special polymeric functional materials. The phenolic hydroxyl groups in its structure can also be linked to photosensitive groups such as DNQ through esterification, and then polymerized with dianhydrides to obtain photosensitive polyimide (PSPI), which has broad application prospects in the display and semiconductor fields.
[0003] The structural formula of 2,2-bis(3-amino-4-hydroxyphenyl)hexafluoropropane is as follows:
[0004]
[0005] Currently, the main method for synthesizing 2,2-bis(3-amino-4-hydroxyphenyl)hexafluoropropane is the initial nitration of hexafluorobisphenol A (bisphenol AF), followed by reduction with hydrogen or hydrazine hydrate (European patent, EP0895985A2; US patents, US7138103B2, US5977413A; Japanese patents, JP2022152421A, JP6211752B2; Chinese patent CN115819254A). This method relies on expensive hexafluorobisphenol A as a raw material, and the initial nitration reaction is highly dangerous. Improper control can easily lead to temperature runaway and explosion. The nitric acid or fuming nitric acid used is a strong acid and highly corrosive reagent. The second step, hydrogenation reduction, generally requires high-pressure equipment, which is specialized equipment and also a highly dangerous reaction. The hydrogen or hydrazine hydrate used is flammable and explosive, as is the metal catalyst. This method is difficult to apply to industrial production. In addition, a method for synthesizing 2,2-bis(3-amino-4-hydroxyphenyl)hexafluoropropane by using halobenzene as a starting material, first condensing it with hexafluoroacetone gas, then hydrolyzing it, and finally catalytically hydrogenating and reducing it (Chinese Patent, CN111302944A) has many reaction steps, all of which involve nitration and hydrogenation reduction, and is also not suitable for industrial production. Summary of the Invention
[0006] In view of this, the present invention aims to provide a new method for preparing 2,2-bis(3-amino-4-hydroxyphenyl)hexafluoropropane, which has a simple synthetic route, improved reaction selectivity and product yield, and is suitable for industrial production.
[0007] To achieve the above objectives, the technical solution of the present invention is implemented as follows:
[0008] A method for preparing 2,2-bis(3-amino-4-hydroxyphenyl)hexafluoropropane includes the following steps:
[0009] S1: Under a protective atmosphere, hexafluoroacetone trihydrate and salicylamide were mixed evenly, stirred and heated, Eaton reagent was added dropwise under controlled temperature. After the reaction was completed, the mixture was cooled, quenched with ice water, filtered, washed with water, slurried with ethanol, and dried to obtain compound (Ⅰ).
[0010]
[0011] S2: Under a protective atmosphere, the compound of formula I obtained in step S1 undergoes a Hoffmann degradation reaction in the presence of hypochlorite and alkali, and the post-treatment yields compound (II) 2,2-bis(3-amino-4-hydroxyphenyl)hexafluoropropane.
[0012]
[0013] The synthesis route is as follows:
[0014]
[0015] Further, in step S1, under a protective gas atmosphere, Eaton reagent was added dropwise to a mixture of hexafluoroacetone trihydrate and salicylamide, and the reaction was maintained at 100°C. After HPLC detection showed the reaction was complete, the mixture was cooled, quenched with ice water, filtered, washed with water, slurried with ethanol, and dried to obtain compound (Ⅰ). By controlling the reaction temperature and the amount of salicylamide, incomplete reaction of the raw material hexafluoroacetone was avoided to the greatest extent possible.
[0016] Furthermore, in step S1, the molar ratio of the raw materials hexafluoroacetone trihydrate and salicylamide is 1.0:(2.2–4.0). Within this range, the hexafluoroacetone reaction is most complete, resulting in the highest yield.
[0017] Further, in step S1, under a protective gas, Eaton reagent is added dropwise to the hexafluoroacetone trihydrate and salicylamide system at a controlled temperature of 80-100℃. After the addition is complete, the system is stirred at 100±5℃.
[0018] Preferably, in step S1, the dripping time is controlled to be 0.5-2 hours.
[0019] Preferably, in step S1, the system is stirred at 100±5℃ for 1-3 hours.
[0020] The hypochlorite in step S2 includes sodium hypochlorite, potassium hypochlorite, copper hypochlorite, calcium hypochlorite, and lithium hypochlorite.
[0021] The base in step S2 includes sodium hydroxide, potassium hydroxide, lithium hydroxide, ammonium hydroxide, sodium carbonate, and potassium carbonate.
[0022] Hypochlorite solution is sodium hypochlorite solution, and alkaline solution is sodium hydroxide solution;
[0023] In step S2, the molar ratio of compound (Ⅰ), hypochlorite, and base is 1.0:(1.1–3.0):(2.2–4.0).
[0024] Further, in step S2, compound (Ⅰ) is added to hypochlorite and alkaline aqueous solution, stirred to dissolve, and heated to 80°C for 4-6 hours.
[0025] Preferably, in step S2, the system is stirred at 80±5℃ for 4-6 hours.
[0026] Furthermore, in both step S1 and step S2, the protective gas is an inert gas, preferably nitrogen.
[0027] Further, the post-processing in step S2 includes cooling, pH adjustment, filtration, water washing, and drying to obtain compound (II) 2,2-bis(3-amino-4-hydroxyphenyl)hexafluoropropane.
[0028] Compared with the prior art, the method for preparing 2,2-bis(3-amino-4-hydroxyphenyl)hexafluoropropane described in this invention has the following advantages:
[0029] This invention uses hexafluoroacetone trihydrate and salicylamide as main raw materials to obtain 2,2-bis(3-carbamoyl-4-hydroxyphenyl)hexafluoropropane through a dehydration condensation reaction, followed by Hoffmann degradation reaction to obtain 2,2-bis(3-amino-4-hydroxyphenyl)hexafluoropropane. The main raw materials are inexpensive and readily available, the reaction steps are simple and safe, the preparation method is easy to implement, the reaction selectivity is higher, there are fewer side reactions, and the reaction yield is high. Therefore, the preparation method described in this invention is novel, the raw materials are readily available, the selectivity is good, the overall preparation cost is low, the yield is high, and it is suitable for industrial production. Detailed Implementation
[0030] It should be noted that, unless otherwise specified, the embodiments and features described in the present invention can be combined with each other.
[0031] The present invention will now be described in detail with reference to the embodiments.
[0032] Unless otherwise defined, the technical terms used in the following embodiments have the same meanings as commonly understood by those skilled in the art to which this invention pertains. Unless otherwise specified, the experimental reagents used in the following embodiments are conventional biochemical reagents; and the experimental methods described are conventional methods.
[0033] The invention will be described in detail below with reference to specific embodiments.
[0034] The synthetic route for 2,2-bis(3-amino-4-hydroxyphenyl)hexafluoropropane is as follows:
[0035]
[0036] Example 1:
[0037] A method for preparing 2,2-bis(3-amino-4-hydroxyphenyl)hexafluoropropane includes the following steps:
[0038] Step (1): The molar ratio of hexafluoroacetone trihydrate to salicylamide was 1.0:2.2. Under nitrogen protection, hexafluoroacetone trihydrate (100 g, 1.0 eq) was added to a 1 L four-necked flask, followed by salicylamide (137.1 g, 2.2 eq) with stirring. The temperature was raised to 80 °C, and Eaton reagent (94.4 g, containing 7.5% P2O5) was added dropwise at 80-100 °C over 1 hour. The reaction was then maintained at 100 °C with stirring for 2 hours. After the reaction was complete as detected by HPLC, the temperature was lowered to 40 °C, and the reaction solution was slowly poured into 1000 mL of ice water. The solution was stirred to quench the reaction, filtered, washed with water, slurried with ethanol, and dried to obtain compound (Ⅰ) 2,2-bis(3-carbamoyl-4-hydroxyphenyl)hexafluoropropane 181.5 g, yield: 94.6%. MS m / z 421 (MH) -
[0039] Its hydrogen nuclear magnetic resonance spectrum is as follows:
[0040] 1 H NMR (600MHz, DMSO-d6, δppm): 6.98 (d, 2H), 7.35 (d, 2H), 7.68 (s, 2H), 7.98 (s, 4H), 11.11 (s, 2H).
[0041] In the above reaction, in order to ensure the complete reaction of the substrate hexafluoroacetone, salicylamide was used in excess and the reaction temperature was set at 100°C to maximize the complete reaction of the raw materials.
[0042] Step (2): The molar ratio of compound (Ⅰ), sodium hypochlorite, and sodium hydroxide was 1.0:1.1:2.2. Under nitrogen protection, 351.9 g (1.1 eq) of 10% sodium hypochlorite aqueous solution was added to a 1 L four-necked flask, followed by the addition of 37.8 g (2.2 eq) of sodium hydroxide with stirring. Finally, compound (Ⅰ) (181.5 g (1.0 eq) was added, stirred to dissolve, and the mixture was heated to 80 °C and reacted for 5 h. After the reaction was completed as detected by HPLC, the temperature was lowered to 20 °C, and hydrochloric acid was added dropwise to adjust the pH to 5-6. The mixture was filtered, washed with water, and dried to obtain 144.0 g of compound 2,2-bis(3-amino-4-hydroxyphenyl)hexafluoropropane, as shown in Formula II, with a yield of 91.5%. MS m / z 365 (MH) -
[0043] Its hydrogen nuclear magnetic resonance spectrum is as follows:
[0044] 1 H NMR (600MHz, DMSO-d6, δppm): 4.66 (s, 4H), 6.45 (d, 2H), 6.59 (s, 2H), 6.69 (d, 2H), 10.06 (s, 2H).
[0045] In the above reaction, in order to ensure that the compound of formula I reacts completely, sodium hypochlorite and sodium hydroxide are in excess and the reaction temperature is 80°C, so as to maximize the complete reaction of the raw materials.
[0046] Example 2:
[0047] A method for preparing 2,2-bis(3-amino-4-hydroxyphenyl)hexafluoropropane includes the following steps:
[0048] Step (1): The molar ratio of hexafluoroacetone trihydrate to salicylamide was 1.0:2.5. Under nitrogen protection, hexafluoroacetone trihydrate (100g, 1 eq) was added to a 1L four-necked flask, followed by salicylamide (155.8g, 2.5 eq) with stirring. The temperature was raised to 80℃, and Eaton reagent (118.0g, containing 7.5% P2O5) was added dropwise at 80-100℃. The addition was completed in 1 hour, and the reaction was maintained at 100℃ with stirring for 2 hours. After the reaction was completed by HPLC, the temperature was lowered to 40℃, and the reaction solution was slowly poured into 1000mL of ice water. The solution was stirred to quench the reaction, filtered, washed with water, slurried with ethanol, and dried to obtain compound (Ⅰ) 2,2-bis(3-carbamoyl-4-hydroxyphenyl)hexafluoropropane 189.2g, yield: 98.6%.
[0049] Step (2): The molar ratio of compound (Ⅰ), sodium hypochlorite, and sodium hydroxide was 1.0:1.5:2.5. Under nitrogen protection, 500.3 g (1.5 eq) of 10% sodium hypochlorite aqueous solution was added to a 1 L four-necked flask, followed by the addition of sodium hydroxide (44.8 g (2.5 eq) with stirring. Finally, compound (Ⅰ) (189.2 g (1.0 eq)) was added, stirred to dissolve, and the mixture was heated to 80 °C and reacted for 5 h. After the reaction was completed as detected by HPLC, the temperature was lowered to 20 °C, and hydrochloric acid was added dropwise to adjust the pH to 5-6. The mixture was filtered, washed with water, and dried to obtain 159.8 g of compound 2,2-bis(3-amino-4-hydroxyphenyl)hexafluoropropane, as shown in Formula II, with a yield of 97.4%.
[0050] Example 3:
[0051] A method for preparing 2,2-bis(3-amino-4-hydroxyphenyl)hexafluoropropane includes the following steps:
[0052] Step (1): The molar ratio of hexafluoroacetone trihydrate to salicylamide was 1.0:3.0. Under nitrogen protection, hexafluoroacetone trihydrate (100g, 1 eq) was added to a 1L four-necked flask, followed by salicylamide (186.9g, 3 eq) with stirring. The temperature was raised to 80℃, and Eaton reagent (141.6g, containing 7.5% P2O5) was added dropwise at 80-100℃. The addition was completed in 1 hour, and the reaction was maintained at 100℃ with stirring for 2 hours. After the reaction was completed by HPLC, the temperature was lowered to 40℃, and the reaction solution was slowly poured into 1000mL of ice water. The solution was stirred to quench the reaction, filtered, washed with water, slurried with ethanol, and dried to obtain compound (Ⅰ) 2,2-bis(3-carbamoyl-4-hydroxyphenyl)hexafluoropropane 185.2g, yield: 96.5%.
[0053] Step (2): The molar ratio of compound (Ⅰ), calcium hypochlorite, and potassium hydroxide was 1.0:2.0:3.0. Under nitrogen protection, 500 g of water and 125.4 g (2.0 eq) of calcium hypochlorite were added to a 2 L four-necked flask. Potassium hydroxide (73.8 g (3.0 eq) was added with stirring, followed by compound (Ⅰ) (185.2 g (1.0 eq). The mixture was stirred until dissolved, and the temperature was raised to 80 °C for 5 h. After HPLC detection, the temperature was lowered to 20 °C, and hydrochloric acid was added dropwise to adjust the pH to 5-6. The mixture was filtered, washed with water, and dried to obtain 158.1 g of compound 2,2-bis(3-amino-4-hydroxyphenyl)hexafluoropropane, as shown in Formula II, with a yield of 98.4%.
[0054] Example 4:
[0055] A method for preparing 2,2-bis(3-amino-4-hydroxyphenyl)hexafluoropropane includes the following steps:
[0056] Step (1): The molar ratio of hexafluoroacetone trihydrate to salicylamide was 1.0:3.5. Under nitrogen protection, hexafluoroacetone trihydrate (100g, 1 eq) was added to a 1L four-necked flask, followed by salicylamide (218.1g, 3.5 eq) with stirring. The temperature was raised to 80℃, and Eaton reagent (188.8g, containing 7.5% P2O5) was added dropwise at 80-100℃. The addition was completed in 1 hour, and the reaction was maintained at 100℃ with stirring for 2 hours. After the reaction was completed by HPLC, the temperature was lowered to 40℃, and the reaction solution was slowly poured into 1000mL of ice water. The solution was stirred to quench the reaction, filtered, washed with water, slurried with ethanol, and dried to obtain compound (Ⅰ) 2,2-bis(3-carbamoyl-4-hydroxyphenyl)hexafluoropropane 173.9g, yield: 90.6%.
[0057] Step (2): The molar ratio of compound (I), copper hypochlorite, and ammonium hydroxide was 1.0:2.5:3.5. Under nitrogen protection, 500 g of water and 171.4 g (2.5 eq) of copper hypochlorite were added to a 2 L four-necked flask. Ammonium hydroxide (50.5 g (3.5 eq) was added with stirring, and finally compound (I) (173.9 g (1.0 eq)) was added. The mixture was stirred to dissolve and then heated to 80 °C for 5 h. After the reaction was completed by HPLC, the temperature was lowered to 20 °C, and hydrochloric acid was added dropwise to adjust the pH to 5-6. The mixture was filtered, washed with water, and dried to obtain 144.0 g of compound 2,2-bis(3-amino-4-hydroxyphenyl)hexafluoropropane, as shown in Formula II, with a yield of 95.5%.
[0058] Example 5:
[0059] A method for preparing 2,2-bis(3-amino-4-hydroxyphenyl)hexafluoropropane includes the following steps:
[0060] Step (1): The molar ratio of hexafluoroacetone trihydrate to salicylamide was 1.0:4.0. Under nitrogen protection, hexafluoroacetone trihydrate (100g, 1 eq) was added to a 1L four-necked flask, followed by salicylamide (249.3g, 4.0 eq) with stirring. The temperature was raised to 80℃, and Eaton reagent (188.8g, containing 7.5% P2O5) was added dropwise at 80-100℃. The addition was completed in 1 hour, and the reaction was maintained at 100℃ with stirring for 2 hours. After the reaction was completed by HPLC, the temperature was lowered to 40℃, and the reaction solution was slowly poured into 1000mL of ice water. The solution was stirred to quench the reaction, filtered, washed with water, slurried with ethanol, and dried to obtain compound (Ⅰ) 2,2-bis(3-carbamoyl-4-hydroxyphenyl)hexafluoropropane 170.6g, yield: 88.9%.
[0061] Step (2): The molar ratio of compound (Ⅰ), lithium hypochlorite, and potassium carbonate was 1.0:3.0:4.0. Under nitrogen protection, 500 g of water and 70.8 g (3.0 eq) of lithium hypochlorite were added to a 2 L four-necked flask. Potassium carbonate (223.3 g (4.0 eq) was added with stirring, followed by compound (Ⅰ) (170.6 g (1.0 eq). The mixture was stirred until dissolved, and the temperature was raised to 80 °C for 5 h. After HPLC detection, the temperature was lowered to 20 °C, and hydrochloric acid was added dropwise to adjust the pH to 5-6. The mixture was filtered, washed with water, and dried to obtain 142.8 g of compound 2,2-bis(3-amino-4-hydroxyphenyl)hexafluoropropane, as shown in Formula II, with a yield of 96.5%.
[0062] Comparative Example 1:
[0063] Step (1): The molar ratio of hexafluoroacetone trihydrate to salicylamide was 1.0:2.5. Under nitrogen protection, hexafluoroacetone trihydrate (100 g, 1 eq) was added to a 1 L four-necked flask, followed by salicylamide (155.8 g, 2.5 eq) with stirring. The temperature was raised to 100 °C and maintained at 100 °C with stirring for 2 h. HPLC analysis showed no formation of compound (Ⅰ).
[0064] Comparative Example 2:
[0065] Step (2): The molar ratio of compound (Ⅰ) to sodium hydroxide was 1.0:2.5. Under nitrogen protection, 500g of water was added to a 1L four-necked flask, followed by the addition of sodium hydroxide (23.7g, 2.5eq) with stirring. Finally, compound (Ⅰ) (100g, 1.0eq) was added, stirred to dissolve, and the mixture was heated to 80℃ and reacted for 5 hours. HPLC analysis showed no formation of compound (Ⅱ).
[0066] Comparative Example 3:
[0067] Step (2): The molar ratio of compound (Ⅰ) to sodium hypochlorite was 1.0:1.5. Under nitrogen protection, 264.4 g of 1.5 eq of 10% sodium hypochlorite solution was added to a 1 L four-necked flask with stirring. Finally, 100 g of compound (Ⅰ) (1.0 eq) was added, stirred to dissolve, and the mixture was heated to 80 °C and reacted for 5 h. HPLC analysis showed that 25% of compound (Ⅱ) was formed.
[0068] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.
Claims
1. A method for preparing 2,2-bis(3-amino-4-hydroxyphenyl)hexafluoropropane, characterized in that: Includes the following steps: S1: Under a protective atmosphere, hexafluoroacetone trihydrate and salicylamide were mixed evenly, stirred and heated, and Eaton reagent was added dropwise to the hexafluoroacetone trihydrate and salicylamide system at 80-100℃. After the addition was complete, the system was stirred at 100±5℃. After the reaction was completed, the mixture was cooled, quenched with ice water, filtered, washed with water, slurried with ethanol, and dried to obtain compound (Ⅰ). (Ⅰ)； S2: Under a protective atmosphere, compound (Ⅰ) obtained in step (1) is added to hypochlorite and alkaline solution, stirred to dissolve and heated to react. After the reaction is completed, post-processing is performed to obtain compound (Ⅱ). (Ⅱ)； The reaction temperature of the heating reaction in step S2 is 80±5℃; The heating reaction in step S2 takes 4-6 hours.
2. The method for preparing 2,2-bis(3-amino-4-hydroxyphenyl)hexafluoropropane according to claim 1, characterized in that: In step S1, the molar ratio of hexafluoroacetone trihydrate to salicylamide is 1.0:(2.2-4.0).
3. The method for preparing 2,2-bis(3-amino-4-hydroxyphenyl)hexafluoropropane according to claim 1, characterized in that: In step S1, Eaton reagent is added dropwise over a period of 0.5-2 hours.
4. The method for preparing 2,2-bis(3-amino-4-hydroxyphenyl)hexafluoropropane according to claim 1, characterized in that: The reaction time of hexafluoroacetone trihydrate and salicylamide in step S1 is 1-3 hours.
5. The method for preparing 2,2-bis(3-amino-4-hydroxyphenyl)hexafluoropropane according to claim 1, characterized in that: The hypochlorite in step S2 is selected from sodium hypochlorite, potassium hypochlorite, copper hypochlorite, calcium hypochlorite, and lithium hypochlorite.
6. The method for preparing 2,2-bis(3-amino-4-hydroxyphenyl)hexafluoropropane according to claim 1, characterized in that: The alkali used in step S2 is selected from sodium hydroxide, potassium hydroxide, lithium hydroxide, ammonium hydroxide, sodium carbonate, and potassium carbonate.
7. The method for preparing 2,2-bis(3-amino-4-hydroxyphenyl)hexafluoropropane according to claim 1, characterized in that: In step S2, the molar ratio of compound (Ⅰ), hypochlorite, and base is 1.0:(1.1–3.0):(2.2–4.0).
8. The method for preparing 2,2-bis(3-amino-4-hydroxyphenyl)hexafluoropropane according to claim 1, characterized in that: The protective gas used in steps S1 and S2 is an inert gas; The post-processing in step S2 includes cooling, pH adjustment, filtration, water washing, and drying to obtain compound (II) 2,2-bis(3-amino-4-hydroxyphenyl)hexafluoropropane.
9. The method for preparing 2,2-bis(3-amino-4-hydroxyphenyl)hexafluoropropane according to claim 8, characterized in that: The protective gas is nitrogen.