Method for synthesizing fluoroalkyl-substituted 4,4'-diaminodiphenylmethane compounds
A safe and efficient method for synthesizing fluoroalkyl-substituted 4,4'-diaminodiphenylmethane compounds using mild conditions and recyclable solvents addresses the limitations of existing methods, enabling high-yield and cost-effective production.
Patent Information
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- HAINAN UNIV
- Filing Date
- 2026-01-09
- Publication Date
- 2026-07-28
AI Technical Summary
Current methods for synthesizing trifluoromethyl-substituted 4,4'-diaminodiphenylmethane are inconvenient, dangerous, and environmentally harmful due to the use of anhydrous HF gas as a catalyst and high temperature/high pressure conditions, and lack methods for synthesizing compounds with other fluoroalkyl groups.
A method involving the reaction of amine compounds with fluorine-containing aldehydes using Lewis or Brønsted acids as catalysts under mild conditions, followed by solvent recovery and recrystallization to produce fluoroalkyl-substituted 4,4'-diaminodiphenylmethane compounds.
This method is safe, efficient, and environmentally friendly, allowing for high yields and reduced solvent costs, making it suitable for large-scale applications.
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Figure 2026122472000001 
Figure 2026122472000002 
Figure 2026122472000003
Abstract
Description
[Technical Field]
[0001] This invention belongs to the field of organic synthesis, and more specifically, relates to a method for synthesizing fluoroalkyl-substituted 4,4'-diaminodiphenylmethane compounds. [Background technology]
[0002] Polyimide is a high-performance engineering material with excellent heat resistance, chemical stability, mechanical properties, electrical properties, radiation resistance, and self-lubricating properties due to its rigid imide structure, and is widely used in industries such as aerospace, machinery, nanotechnology, separation membranes, electrical engineering, and microelectronics. However, polyimide has a high melting point, low solubility, is difficult to mold and process, and has high production costs. Furthermore, its highly conjugated aromatic structure and intermolecular charge transfer complexes make it very susceptible to staining, reduce optical transparency, and have a high dielectric constant, limiting its application in technological fields such as flexible electronics and flexible circuit boards.
[0003] By introducing fluorine-containing substituents into the molecular structure of polyimides, these drawbacks can be effectively compensated for, reducing light loss, dielectric constant, and hygroscopicity, while improving solubility, transparency, and thermal stability, thus providing unique advantages and broad development possibilities in fields such as optoelectronics and aerospace. Trifluoromethyl-substituted 4,4'-diaminodiphenylmethane is an important fluorine-containing polyimide monomer. Patent application "Method for producing 1,1,1-trifluoro-2,2-diarylethane and 1,1,1-trifluoro-2,2-diarylethane" (publication number CN113396137A) uses aniline and trifluoroacetaldehyde as raw materials. Under anhydrous conditions, it requires the introduction of anhydrous HF gas as a catalyst, the addition of a large amount of trifluoromethanesulfonic acid, and the reaction to be carried out under high temperature and high pressure using special equipment such as a stainless steel autoclave, making the manufacturing process very inconvenient, dangerous, and complex. After the reaction, neutralization with a 48% potassium hydroxide aqueous solution is required, resulting in the generation of a large amount of wastewater. Furthermore, because HF gas is used as a catalyst, it is highly corrosive and dangerous, difficult to recycle, and causes serious environmental pollution.
[0004] As described above, current methods for synthesizing trifluoromethyl-substituted 4,4'-diaminodiphenylmethane have several limitations. Therefore, the development of simple, highly safe, low-cost, and environmentally friendly synthetic methods for trifluoromethyl-substituted 4,4'-diaminodiphenylmethane and other fluoroalkyl-substituted 4,4'-diaminodiphenylmethanes is extremely important. Furthermore, there are currently no reports on the synthesis of 4,4'-diaminodiphenylmethane compounds substituted with fluoroalkyl groups such as difluoromethyl or pentafluoroethyl groups. [Overview of the Initiative] [Problems that the invention aims to solve]
[0005] This invention provides a method for synthesizing fluoroalkyl-substituted 4,4'-diaminodiphenylmethane compounds. This method uses readily available starting materials, is easy to operate, requires mild reaction conditions, is highly safe, yields high reaction yields, is atomically economical, and has potential for large-scale applications. [Means for solving the problem]
[0006] To achieve the above objectives, the technical solutions employed by the present invention are as follows.
[0007] A method for synthesizing fluoroalkyl-substituted 4,4'-diaminodiphenylmethane compounds, The process includes the step of reacting an amine compound with a fluorine-containing aldehyde compound in an organic solvent under the action of a catalyst, and after the reaction is complete, performing post-treatment to obtain the fluoroalkyl-substituted 4,4'-diaminodiphenylmethane compound having a structure represented by the following general formula [1]. [ka] (In the general formula [1], n1 and n2 are independent integers from 0 to 4, and R 1 If multiple instances exist, each independently represents a substituent. R 1 These are independently selected from hydrogen, alkyl groups, alkoxy groups, cycloalkyl groups, aryl groups, propenyl groups, halogens, hydroxyl groups, benzyl groups, thioalkyl groups, and ester groups. R f These are independently selected from difluoromethyl, trifluoromethyl, trifluoroethyl, tetrafluoroethyl, pentafluoroethyl, heptafluoropropyl, and nonafluorobutyl groups. X is independently selected from a methylene group, oxygen, or sulfur.
[0008] Preferably, the amine compound includes monosubstituted, polysubstituted, or unsubstituted aromatic amine compounds and diphenylamine compounds.
[0009] More preferably, in the monosubstituted, polysubstituted, or unsubstituted aromatic amine compounds, each substituent is independently selected from hydrogen, methyl group, ethyl group, t-butyl group, isopropyl group, alkoxy group, cycloalkyl group, phenyl group, propenyl group, halogen, hydroxy group, benzyl group, thioalkyl group, ester group, and trifluoromethoxy group, and the diphenylamine compounds are diaminodiphenylmethane, oxydiphenylamine, and thiodiphenylamine.
[0010] Preferably, the fluorine-containing aldehyde compound includes difluoroacetaldehyde hydrate, difluoroacetaldehyde ethylhemiaacetal, trifluoroacetaldehyde hydrate, trifluoroacetaldehyde methylhemiaacetal, trifluoroacetaldehyde ethylhemiaacetal, 3,3,3-trifluoropropionaldehyde, 2,2,3,3-tetrafluoropropionaldehyde hydrate, pentafluoropropionaldehyde hydrate, heptafluorobutyraldehyde hydrate, or nonafluorovaleraldehyde hydrate.
[0011] Preferably, the catalyst is a Lewis acid or a Brønsted acid.
[0012] More preferably, the Lewis acid is phenylboronic acid, boric acid, trimethyl borate, triethyl borate, triisopropyl borate, tributyl borate, triphenyl borate, boron trifluoride ether, tris(2,4-bis(trifluoromethyl)phenyl)borane, tris(pentafluorophenyl)borane, tris(2,2,2-trifluoroethyl)borate, triphenylborane, tris(hexafluoroisopropyl)borate, tris(2,3,5,6-tetrafluoro-4-(trifluoromethyl)phenyl) Borane, trimethylsilyl trifluoromethanesulfonate, tert-butyldimethylsilyl trifluoromethanesulfonate, trimethylsilyl acetate, trimethylsilylmethanesulfonate, N-(trimethylsilyl)bis(trifluoromethanesulfonyl)imine, (pentafluorophenyl)bis(trifluoromethanesulfonyl)trimethylsilylmethane, di-tert-butylisobutylsilyl trifluoromethanesulfonate, tert-butyldiphenylsilyl trifluoromethanesulfonate, 2- (Trimethylsilyl)phenyltrifluoromethanesulfonate, triisopropylsilyltrifluoromethanesulfonate, diisopropylsilylbis(trifluoromethanesulfonate), diethylisopropylsilyltrifluoromethanesulfonate, di-tert-butylsilylbis(trifluoromethanesulfonic acid), triethylsilyltrifluoromethanesulfonate, tris(2,6-difluorophenyl)borane, tris(2,5-bis(trifluoromethyl)phenyl)borane, 2,4,6-tris(3- Selected from (trifluoromethyl)phenyl)-1,3,5,2,4,6-trioxatriborinane, triphenylmethyltetra(pentafluorophenyl)borate, bis(perfluorophenyl)borane, tris(2,4,6-trifluorophenyl)borane, tris[3,5-bis(trifluoromethyl)phenyl]borane, tris(2,2',2''-perfluorobiphenyl)borane, bis(pentafluorophenyl)-(2-perfluorobiphenyl)borane, or tris(2-perfluoronaphthyl)borane. The Brønsted acid is selected from acetic acid, benzoic acid, benzenesulfonic acid, p-toluenesulfonic acid, methylsulfonic acid, camphorsulfonic acid, Amberlyst 15 ion exchange resin, diphenyl phosphate, hydrogen phosphate-1,1'-binaphthyl-2,2'-diyl, trifluoroacetic acid, trifluoromethanesulfonic acid, lactic acid, oxalic acid, sulfuric acid, hydrochloric acid, perchloric acid, phosphoric acid, or polyphosphate.
[0013] Preferably, the organic solvent is 2,2-difluoroethanol, hexafluoroisopropanol, hexafluoro-2-methylisopropanol, hexafluoro-2-phenylisopropanol, trifluoroethanol, perfluoroalkylethanol, perfluorotert-butanol, ethylene glycol, tetrafluoropropanol, tetrafluorobutanediol, hexafluorobutanol, or octafluoropentanol.
[0014] Preferably, the reaction temperature is room temperature to 130°C, and the reaction time is 12 to 24 hours. More preferably, the reaction is carried out at 45 to 90°C for 12 to 20 hours.
[0015] Preferably, the molar ratio of the amine compound to the fluorine-containing aldehyde compound is 1 to 2.4:1.
[0016] Preferably, the molar ratio of the fluorine-containing aldehyde compound to the catalyst is 1:0 to 0.2.
[0017] Preferably, the post-treatment includes removing the solvent under reduced pressure after the reaction is complete, and recrystallizing the crude reaction product to obtain a fluoroalkyl-substituted 4,4'-diaminodiphenylmethane compound.
[0018] More preferably, the solvent used for recrystallization includes ethanol, methanol, toluene, ethyl acetate, and chloroform.
[0019] More preferably, after the reaction is complete, the fluoroalcohol solvent can be recovered by a simple distillation operation. [Effects of the Invention]
[0020] Compared to the conventional technology, the beneficial effects of the present invention are as follows:
[0021] This invention provides a method for synthesizing fluoroalkyl-substituted 4,4'-diaminodiphenylmethane compounds that effectively solves the problems of conventional methods, such as the need for anhydrous reaction conditions, the use of hydrogen fluoride as a catalyst, high temperature and pressure, high operational risk, and complex post-treatment. Because this invention uses Lewis acids or Brønsted acids as catalysts, the reaction does not require anhydrous conditions, the reaction conditions are mild, the operation is simple, the reaction efficiency is high, the raw materials are inexpensive and readily available, it is atomically economical, and no waste is generated, making it suitable for large-scale applications. Furthermore, since the fluoroalcohol solvent can be recycled by a simple distillation operation, solvent costs are significantly reduced, process safety is improved, and it is advantageous for efficient and environmentally friendly industrial production. [Modes for carrying out the invention]
[0022] The present invention will be described in detail below with reference to specific embodiments. The following specific embodiments will be helpful to those skilled in the art in understanding the present invention, but will not limit the present invention in any form. [Examples]
[0023] [ka] 1000 mL reaction flask was successively added with aniline (0.76 mol, 2 equiv), trifluoroacetaldehyde hydrate (44.1 g, 0.38 mol), trifluoroethanol (640 mL), and phenylboronic acid (0.038 mol), and reacted at 45 °C. As a result of monitoring the reaction by TLC spotting, the reaction was completed after 12 hours. After the reaction was completed, the solvent was recovered by a rotary evaporator, and the crude reaction product was recrystallized with toluene to obtain 80.8 g of the product (4,4’-(2,2,2-trifluoroethane-1,1-diyl)dianiline) shown by the above formula in a yield of 80%. 1 1H NMR (400 MHz, CDCl3) δ 7.13 (d, J = 8.2 Hz, 4H), 6.64 (d, J = 8.4 Hz, 4H), 4.46 (q, J = 10.1 Hz, 1H), 3.65 (s, 4H); 19 19F NMR (376 MHz, CDCl3) δ -66.41 (d, J = 9.9 Hz, 3F); 13 13C NMR (100 MHz, CDCl3) δ 145.8, 129.9, 126.6 (d, 1 J C-F = 281.8 Hz), 125.8, 115.1, 53.9 (q, 2 J C-F = 27.3 Hz); HRMS (ESI) m / z: [M + H] + Calculated C 14 H 14 F3N2 267.1104; Measured value: 267.1108.
Example
[0024]
Chemical formula
[0025] [ka] In a 1000 mL reaction flask, 3-methylaniline (0.76 mol, 2 equiv), trifluoroacetaldehyde ethylhemiaacetal (54.7 g, 0.38 mol), hexafluoroisopropanol (640 mL), and tris(2,4-bis(trifluoromethyl)phenyl)borane (0.019 mol) were added sequentially and the reaction was carried out at 65 °C. The reaction was monitored by TLC spotting, and it was confirmed that the reaction was complete after 14 hours. After the reaction was complete, the solvent was recovered using a rotary evaporator, and the crude reaction product was recrystallized with ethyl acetate to obtain 72.6 g of the product (4,4'-(2,2,2-trifluoroethane-1,1-diyl)bis(3-methylaniline)) shown in the above formula in a yield of 65%. 1 H NMR(400 MHz,CDCl3)δ 7.17(d,J=8.3 Hz,2H),6.53 - 6.46(m,4H),4.82(q,J=9.7 Hz,1H),3.59(s,4H),2.21(s,6H); 19 F NMR(376 MHz,CDCl3)δ -65.10(d,J=9.8 Hz,3F); 13 C NMR(100 MHz,CDCl3)δ 145.5,137.8,129.6,127.2(d, 1 J C-F =282.2 Hz),124.3,117.2,112.8,45.9(q, 2 J C-F= 26.8 Hz),19.7;HRMS(ESI)m / z:[M+H] + Calculated value C 16 H 18 F3N2295.1417; Measured value: 295.1416. [Examples]
[0026] [ka] In a 1000 mL reaction flask, 2-methoxyaniline (0.84 mol, 2.2 equiv), trifluoroacetaldehyde hydrate (44.1 g, 0.38 mol), perfluorotert-butanol (640 mL), and trimethyl borate (0.038 mol) were added sequentially. The reaction was carried out at 50°C, and the reaction was monitored by TLC spotting. The reaction was completed after 12 hours. After the reaction was complete, the solvent was recovered using a rotary evaporator, and the crude reaction product was recrystallized with methanol to obtain 107.8 g of the product shown in the above formula in 87% yield. [Examples]
[0027] [ka] In a 1000 mL reaction flask, 2-methylthioaniline (0.76 mol, 2 equiv), trifluoroacetaldehyde ethylhemiaacetal (54.7 g, 0.38 mol), hexafluoroisopropanol (640 mL), and triethyl borate (0.038 mol) were added sequentially. The reaction was carried out at 90°C, and the reaction was monitored by TLC spotting. The reaction was completed after 12 hours. After the reaction was complete, the solvent was recovered using a rotary evaporator, and the crude reaction product was recrystallized with ethanol to obtain 83.3 g of the product shown in the above formula in a yield of 61%. [Examples]
[0028] [ka] In a 1000 mL reaction flask, 2-aminobiphenyl (0.76 mol, 2 equiv), trifluoroacetaldehyde methylhemiaacetal (49.4 g, 0.38 mol), 2,2-difluoroethanol (640 mL), and tris(2,2,2-trifluoroethyl)borate (0.038 mol) were added sequentially and the reaction was carried out at 80°C. The reaction was monitored by TLC spotting, and it was confirmed that the reaction was complete after 15 hours. After the reaction was complete, the solvent was recovered using a rotary evaporator, and the crude reaction product was recrystallized with chloroform to obtain 150.9 g of the product shown in the above formula in 95% yield. [Examples]
[0029] [ka] In a 1000 mL reaction flask, 2-bromoaniline (0.76 mol, 2 equiv), trifluoroacetaldehyde methylhemiaacetal (49.4 g, 0.38 mol), hexafluoro-2-methylisopropanol (640 mL), and tris(hexafluoroisopropyl) borate (0.076 mol) were added sequentially. The reaction was carried out at 65°C, and the reaction was monitored by TLC spotting. The reaction was completed after 12 hours. After the reaction was complete, the solvent was recovered using a rotary evaporator, and the crude reaction product was recrystallized with ethanol to obtain 82.5 g of the product shown in the above formula in a yield of 51%. [Examples]
[0030] [ka] In a 1000 mL reaction flask, 3,5-dimethylaniline (0.76 mol, 2 equiv), trifluoroacetaldehyde hydrate (44.1 g, 0.38 mol), hexafluoroisopropanol (640 mL), and boron trifluoride ether (0.038 mol) were added sequentially. The reaction was carried out at 50°C, and the reaction was monitored by TLC spotting. The reaction was completed after 15 hours. After the reaction was complete, the solvent was recovered using a rotary evaporator, and the crude reaction product was recrystallized with ethanol to obtain 118.7 g of the product (4,4'-(2,2,2-trifluoroethane-1,1-diyl)bis(2,6-dimethylaniline)) shown in the above formula in 97% yield. 1 H NMR(400 MHz,CDCl3)δ 6.95(s,4H),4.38(q,J=10.4 Hz,1H),3.59(s,4H),2.17(s,12H); 19 F NMR(376 MHz,CDCl3)δ -66.09(d,J=10.3 Hz,3F); 13 C NMR(100 MHz,CDCl3)δ 142.1,128.8,126.7(d, 1 J C-F =281.1 Hz),125.4,121.7,54.2(q, 2 J C-F =27.0 Hz),17.7;HRMS(ESI)m / z:[M+H] + Calculated value C 18 H 22 F3N2323.1730; Measured value: 323.1731. [Examples]
[0031] [ka] In a 1000 mL reaction flask, 2-chloro-6-methylaniline (0.76 mol, 2 equiv), trifluoroacetaldehyde hydrate (44.1 g, 0.38 mol), perfluoroalkylethanol (640 mL), and triisopropylsilyltrifluoromethanesulfonate (0.038 mol) were added sequentially and the reaction was carried out at 65 °C. The reaction was monitored by TLC spotting, and it was confirmed that the reaction was complete after 18 hours. After the reaction was complete, the solvent was recovered using a rotary evaporator, and the crude reaction product was recrystallized in toluene to obtain 132.1 g of the product (4,4'-(2,2,2-trifluoroethane-1,1-diyl)bis(2-chloro-6-methylaniline)) shown in the above formula in 96% yield. 1 H NMR(400 MHz,CDCl3)δ 7.12(s,2H),6.92(s,2H),4.35(q,J=9.9 Hz,1H),4.00(s,4H),2.18(s,6H); 19 F NMR(376 MHz,CDCl3)δ -66.29(d,J=9.8 Hz,3F); 13 C NMR(100 MHz,CDCl3)δ 140.8,129.3,127.3,126.1(d, 1 J C-F =281.8 Hz),125.3,123.6,119.0,53.5(q, 2 J C-F =27.6 Hz),18.1;HRMS(ESI)m / z:[M+H] + Calculated value C 16 H 16 F3N2Cl2363.0637; Measured value: 363.0640. [Examples]
[0032] [ka] In a 1000 mL reaction flask, 2-methyl-3-fluoroaniline (0.76 mol, 2 equiv), trifluoroacetaldehyde ethylhemiaacetal (54.7 g, 0.38 mol), hexafluoroisopropanol (640 mL), and bis(perfluorophenyl)borane (0.019 mol) were added sequentially and reacted at 45°C. The reaction was monitored by TLC spotting, and it was confirmed that the reaction was complete after 12 hours. After the reaction was complete, the solvent was recovered using a rotary evaporator, and the crude reaction product was recrystallized with ethanol to obtain 95.3 g of the product shown in the above formula in 76% yield. [Examples]
[0033] [ka] In a 1000 mL reaction flask, o-benzylaniline (0.8 mol, 2.1 equiv), trifluoroacetaldehyde ethylhemiaacetal (54.7 g, 0.38 mol), tetrafluoropropanol (640 mL), and tert-butyldimethylsilyltrifluoromethanesulfonate (0.038 mol) were added sequentially and the reaction was carried out at 65 °C. The reaction was monitored by TLC spotting, and it was confirmed that the reaction was complete after 18 hours. After the reaction was complete, the solvent was recovered using a rotary evaporator, and the crude reaction product was recrystallized with ethanol to obtain 155.9 g of the product (4,4'-(2,2,2-trifluoroethane-1,1-diyl)bis(2-benzylaniline)) shown in the above formula in 92% yield. 1 H NMR(400 MHz,CDCl3)δ 7.30(t,J=7.2 Hz,4H),7.26 - 7.15(m,6H),7.14 - 7.07(m,4H),6.64(d,J=8.1 Hz,2H),4.49(q,J=10.2 Hz,1H),3.90(s,4H),3.37(s,4H); 19 F NMR(376 MHz,CDCl3)δ -66.24(d,J=10.1 Hz,3F); 13C NMR(100 MHz,CDCl3)δ 144.2,139.0,131.7,128.7,128.4,128.2,126.4,126.6(d, 1 J C-F =281.9 Hz),126.0,124.9,115.9,54.1(q, 2 J C-F= 27.2 Hz),38.2;HRMS(ESI)m / z:[M+H] + Calculated value C 28 H 26 F3N2447.2043; Measured value: 447.2050. [Examples]
[0034] [ka] In a 1000 mL reaction flask, 3,3'-oxydiphenylamine (0.38 mol, 1 equiv), trifluoroacetaldehyde hydrate (44.1 g, 0.38 mol), tetrafluoropropanol (640 mL), and boric acid (0.038 mol) were added sequentially. The reaction was carried out at 65°C, and the reaction was monitored by TLC spotting. The reaction was completed after 18 hours. After the reaction was complete, the solvent was recovered using a rotary evaporator, and the crude reaction product was recrystallized with ethanol to obtain 54.2 g of the product (9-(trifluoromethyl)-9H-xanthene-3,6-diamine) shown in the above formula in 51% yield. 1 H NMR(400 MHz,CDCl3)δ 7.30(d,J=8.3 Hz,1H),7.11(t,J=8.1 Hz,1H),6.47 - 6.40(m,2H),6.32(s,1H),6.13(d,J=1.9 Hz,1H),5.28(q,J=7.0 Hz,1H),3.73(s,4H). 19 F NMR(376 MHz,CDCl3)δ -78.02(d,J=6.8 Hz,3F). 13 C NMR(100 MHz,CDCl3)δ 156.7,148.0,130.5,129.8(d, 1 J C-F=281.5 Hz),110.0,105.1,67.9(q, 2 J C-F =27.2 Hz),29.7. HRMS(ESI)m / z:[M+H] + Calculated value C 14 H 12 F3N2O 281.0896; Measured value: 281.0899. [Examples]
[0035] [ka] In a 1000 mL reaction flask, aniline (0.8 mol, 2 equiv), difluoroacetaldehyde ethylhemiaacetal (50.4 g, 0.4 mol), hexafluoroisopropanol (640 mL), and triphenylborane (0.08 mol) were added sequentially and the reaction was carried out at 50°C. The reaction was monitored by TLC spotting, and it was determined that the reaction was complete after 18 hours. After the reaction was complete, the solvent was recovered using a rotary evaporator, and the crude reaction product was recrystallized with ethanol to obtain 99.2 g of the product (4,4'-(2,2-difluoroethane-1,1-diyl)dianiline) shown in the above formula in 96% yield. 1 H NMR(400 MHz,CDCl3)δ 7.07(d,J=8.4 Hz,4H),6.67 - 6.62(m,4H),6.19(td,J=56.3,4.4 Hz,1H),4.19(td,J=16.2,4.3 Hz,1H),3.63(s,4H); 19 F NMR(376 MHz,CDCl3)δ -118.04(dd,J=56.6,16.2 Hz,2F); 13 C NMR(100 MHz,CDCl3)δ 145.5,129.8,127.5(t, 3 J C-F =3.5 Hz), 117.3(t, 1 J C-F =244.9 Hz),115.2,53.4(t, 2 J C-F=20.5 Hz);HRMS(ESI)m / z:[M+H] + Calculated value C 14 H 15 F2N2249.1198; measured value; 249.1195. [Examples]
[0036] [ka] In a 1000 mL reaction flask, 2-methylaniline (0.8 mol, 2 equiv), difluoroacetaldehyde hydrate (39.2 g, 0.4 mol), hexafluoroisopropanol (640 mL), and tris(pentafluorophenyl)borane (0.04 mol) were added sequentially. The reaction was carried out at 65°C, and the reaction was monitored by TLC spotting. The reaction was completed after 12 hours. After the reaction was complete, the solvent was recovered using a rotary evaporator, and the crude reaction product was recrystallized with ethyl acetate to obtain 104.9 g of the product shown in the above formula in 95% yield. [Examples]
[0037] [ka] In a 1000 mL reaction flask, 2-t-butylaniline (0.8 mol, 2 equiv), difluoroacetaldehyde hydrate (39.2 g, 0.4 mol), hexafluorobutanol (640 mL), and trimethylsilyltrifluoromethanesulfonate (0.04 mol) were added sequentially and reacted at 90°C. The reaction was monitored by TLC spotting, and it was confirmed that the reaction was complete after 14 hours. After the reaction was complete, the solvent was recovered using a rotary evaporator, and the crude reaction product was recrystallized with ethanol to obtain 138.2 g of the product shown in the above formula in 96% yield. [Examples]
[0038] [ka] In a 1000 mL reaction flask, 3-fluoroaniline (0.8 mol, 2 equiv), difluoroacetaldehyde ethylhemiaacetal (50.4 g, 0.4 mol), hexafluoroisopropanol (640 mL), and p-toluenesulfonic acid (0.04 mol) were added sequentially and the reaction was carried out at 50°C. The reaction was monitored by TLC spotting, and it was determined that the reaction was complete after 14 hours. After the reaction was complete, the solvent was recovered using a rotary evaporator, and the crude reaction product was recrystallized with ethanol to obtain 77.2 g of the product shown in the above formula in a yield of 68%. [Examples]
[0039] [ka] In a 1000 mL reaction flask, methyl 2-aminobenzoate (0.96 mol, 2.4 equiv), difluoroacetaldehyde ethylhemiaacetal (50.4 g, 0.4 mol), trifluoroethanol (640 mL), and N-(trimethylsilyl)bis(trifluoromethanesulfonyl)imine (0.04 mol) were added sequentially and the reaction was carried out at 65 °C. The reaction was monitored by TLC spotting, and it was confirmed that the reaction was complete after 20 hours. After the reaction was complete, the solvent was recovered using a rotary evaporator, and the crude reaction product was recrystallized with ethanol to obtain 75.7 g of the product shown in the above formula (Dimethyl 5,5'-(2,2-difluoroethane-1,1-diyl)bis(2-aminobenzoate)) in a yield of 52%. 1 H NMR(400 MHz,CDCl3)δ 7.79(d,J=2.2 Hz,2H),7.17(dd,J=8.5,2.2 Hz,2H),6.63(d,J=8.5 Hz,2H),6.20(td,J=56.0,4.1 Hz,1H),5.70(s,4H),4.17(td,J=16.3,4.0 Hz,1H),3.86(s,6H); 19 F NMR(376 MHz,CDCl3)δ -118.44(dd,J=56.1,16.3 Hz,2F); 1313C NMR (100 MHz, CDCl3) δ 168.3, 149.6, 134.6, 131.4, 124.8 (t, 3 J C-F = 3.4 Hz), 117.2, 116.9 (t, 1 J C-F = 245.2 Hz), 110.6, 53.0 (t, 2 J C-F = 20.7 Hz), 51.6; HRMS (ESI) m / z: [M+H] + Calculated for C 18 H 19 F2N2O4 365.1307; found; 365.1305.
Example
[0040]
Chem.
Example
[0041]
Chem.
[0042] [ka] In a 1000 mL reaction flask, aniline (0.64 mol, 2 equiv), pentafluoropropionaldehyde hydrate (53 g, 0.32 mol), hexafluoroisopropanol (640 mL), and tris(2,3,5,6-tetrafluoro-4-(trifluoromethyl)phenyl)borane (0.032 mol) were added in sequence and the reaction was carried out at 65 °C. The reaction was monitored by TLC spotting, and it was confirmed that the reaction was complete after 14 hours. After the reaction was complete, the solvent was recovered using a rotary evaporator, and the crude reaction product was recrystallized with ethanol to obtain 68.8 g of the product shown in the above formula in a yield of 68%. Clearly, the above embodiments of the present invention are merely examples to illustrate the invention more clearly and do not limit the embodiments of the present invention. Those skilled in the art will be able to make other different forms of modifications and variations based on the above description. Not all possible methods of implementation are covered here. All obvious modifications and variations derived from the technical solutions of the present invention are all within the scope of protection of the present invention.
Claims
1. A method for synthesizing fluoroalkyl-substituted 4,4'-diaminodiphenylmethane compounds, The process includes the step of reacting an aromatic primary amine compound with difluoroacetaldehyde hydrate, trifluoroacetaldehyde hydrate, 2,2,3,3-tetrafluoropropionaldehyde hydrate, pentafluoropropionaldehyde hydrate, heptafluorobutyraldehyde hydrate, or nonafluorovaleraldehyde hydrate in an organic solvent under the action of a catalyst, and after the reaction is complete, post-treatment to obtain the fluoroalkyl-substituted 4,4'-diaminodiphenylmethane compound having a structure represented by the following general formula [1], The catalyst is a Lewis acid or a Brønsted acid. The organic solvent is 2,2-difluoroethanol, hexafluoroisopropanol, hexafluoro-2-methylisopropanol, hexafluoro-2-phenylisopropanol, trifluoroethanol, perfluoroalkylethanol, perfluorotert-butanol, tetrafluoropropanol, tetrafluorobutanediol, hexafluorobutanol, or octafluoropentanol. The post-treatment includes removing the solvent under reduced pressure after the reaction is complete, and recrystallizing the reaction crude product to obtain a fluoroalkyl-substituted 4,4'-diaminodiphenylmethane compound, and the fluoroalcohol solvent can be recovered by a simple distillation operation after the reaction is complete. 【Chemistry 1】 (In general formula [1], n １ and n ２ Each of these is an integer between 0 and 4, and R １ If multiple instances exist, each independently represents a substituent. R １ These are independently selected from hydrogen, alkyl groups, alkoxy groups, cycloalkyl groups, aryl groups, propenyl groups, halogens, hydroxyl groups, benzyl groups, and thioalkyl groups. R ｆ These are independently selected from difluoromethyl, trifluoromethyl, tetrafluoroethyl, pentafluoroethyl, heptafluoropropyl, and nonafluorobutyl groups. X is independently selected from a methylene group, oxygen, or sulfur.
2. R １ A method for synthesizing a fluoroalkyl-substituted 4,4'-diaminodiphenylmethane compound according to claim 1, characterized in that the compound is independently selected from hydrogen, a methyl group, an ethyl group, a t-butyl group, an isopropyl group, an alkoxy group, a cycloalkyl group, a phenyl group, a propenyl group, a halogen, a hydroxyl group, a benzyl group, and a thioalkyl group.
3. The Lewis acids mentioned above include phenylboronic acid, boric acid, trimethyl borate, triethyl borate, triisopropyl borate, tributyl borate, triphenyl borate, boron trifluoride ether, tris(2,4-bis(trifluoromethyl)phenyl)borane, tris(pentafluorophenyl)borane, tris(2,2,2-trifluoroethyl)borate, triphenylborane, tris(hexafluoroisopropyl)borate, tris(2,3,5,6-tetrafluoro-4-(trifluoromethyl)phenyl)borane, trimethyl 1-Tilsilyltrifluoromethanesulfonate, tert-butyldimethylsilyltrifluoromethanesulfonate, trimethylsilyl acetate, trimethylsilylmethanesulfonate, N-(trimethylsilyl)bis(trifluoromethanesulfonyl)imine, (pentafluorophenyl)bis(trifluoromethanesulfonyl)trimethylsilylmethane, di-tert-butylisobutylsilyltrifluoromethanesulfonate, tert-butyldiphenylsilyltrifluoromethanesulfonate, 2-(trimethyl Lucilyl)phenyltrifluoromethanesulfonate, triisopropylsilyltrifluoromethanesulfonate, diisopropylsilylbis(trifluoromethanesulfonate), diethylisopropylsilyltrifluoromethanesulfonate, di-tert-butylsilylbis(trifluoromethanesulfonic acid), triethylsilyltrifluoromethanesulfonate, tris(2,6-difluorophenyl)borane, tris(2,5-bis(trifluoromethyl)phenyl)borane, 2,4,6-tris(3-(tri Selected from fluoromethyl)phenyl)-1,3,5,2,4,6-trioxatriborinane, triphenylmethyltetra(pentafluorophenyl)borate, bis(perfluorophenyl)borane, tris(2,4,6-trifluorophenyl)borane, tris[3,5-bis(trifluoromethyl)phenyl]borane, tris(2,2',2''-perfluorobiphenyl)borane, bis(pentafluorophenyl)-(2-perfluorobiphenyl)borane, or tris(2-perfluoronaphthyl)borane. A method for synthesizing a fluoroalkyl-substituted 4,4'-diaminodiphenylmethane compound according to claim 1, characterized in that the Brønsted acid is selected from acetic acid, benzoic acid, benzenesulfonic acid, p-toluenesulfonic acid, methylsulfonic acid, camphorsulfonic acid, Amberlyst 15 ion exchange resin, diphenyl phosphate, hydrogen phosphate-1,1'-binaphthyl-2,2'-diyl, trifluoroacetic acid, trifluoromethanesulfonic acid, lactic acid, oxalic acid, sulfuric acid, hydrochloric acid, perchloric acid, phosphoric acid, or polyphosphate.
4. A method for synthesizing a fluoroalkyl-substituted 4,4'-diaminodiphenylmethane compound according to any one of claims 1 to 3, characterized in that the reaction temperature is room temperature to 130°C and the reaction time is 12 to 24 hours.
5. A method for synthesizing a fluoroalkyl-substituted 4,4'-diaminodiphenylmethane compound according to claim 1, characterized in that the molar ratio of the aromatic primary amine compound to difluoroacetaldehyde hydrate, trifluoroacetaldehyde hydrate, 2,2,3,3-tetrafluoropropionaldehyde hydrate, pentafluoropropionaldehyde hydrate, heptafluorobutyraldehyde hydrate, or nonafluorovaleraldehyde hydrate is 1 to 2.4:
1.
6. A method for synthesizing a fluoroalkyl-substituted 4,4'-diaminodiphenylmethane compound according to claim 1 or 5, characterized in that the molar ratio of the difluoroacetaldehyde hydrate, trifluoroacetaldehyde hydrate, 2,2,3,3-tetrafluoropropionaldehyde hydrate, pentafluoropropionaldehyde hydrate, heptafluorobutyraldehyde hydrate, or nonafluorovaleraldehyde hydrate to the catalyst is 1:0 to 0.2.