Synthesis method of 2-aryl-2-(4-aminophenyl)propane

Abstract

The present invention provides a method for preparing 2-aryl-2-(4-aminophenyl)propane. Using inexpensive cumene phenol as a raw material, the method uses a novel step design to synthesize 2-aryl-2-(4-aminophenyl)propane, particularly the commonly used 2-phenyl-2-(4-aminophenyl)propane, with an overall yield exceeding 50%. This method solves the problem of preparing this key intermediate and is of great significance in the synthesis of related OLED materials.

Description

Technical Field

[0001] The present invention provides a method for synthesizing 2-aryl-2-(4-aminophenyl)propane (or 3-aryl-2-(4-aminophenyl)propane) by using cheap arylphenol as raw material and adopting new technology through a series of experimental operations. The product purity is above 99% and the comprehensive yield is above 50%. Background Art

[0002] 2-Aryl-2-(4-aminophenyl)propane is a very critical intermediate in the synthesis of OLED materials, especially in the synthesis of BN-based blue fluorescent dyes. For example, 2-phenyl-2-(4-aminophenyl)propane has the following uses:

[0003]

[0004] Similar fluorescent dyes include:

[0005] wait.

[0006] Although 2-aryl-2-(4-aminophenyl)propane compounds such as 2-phenyl-2-(4-aminophenyl)propane have great application value in the synthesis of blue light dyes, they are rarely sold on the market.

[0007] In addition, there are very few reports on the synthesis method in the existing literature. The following synthesis route is reported in the prior art document 1:

[0008]

[0009] The following synthesis route is reported in prior art document 2

[0010]

[0011] However, these methods have very low yields and the reaction conditions are not suitable for large-scale industrial production. Therefore, it is very urgent to develop a method suitable for industrial production that can synthesize 2-aryl-2-(4-aminophenyl)propane with high yield.

[0012] Prior art document 1: Organic Letters (2019), 21(22), 9055-9059

[0013] Prior art document 2: JP2011195462A Summary of the Invention

[0014] In this specification, the expression of Ca to Cb means that the number of carbon atoms in the group is a to b. Unless otherwise specified, the number of carbon atoms in the group generally does not include the number of carbon atoms in the substituent.

[0015] In this specification, the expression of a ring structure crossed by “—” indicates that the connection site is any position on the ring structure that can form a bond.

[0016] In this specification, “each independently” means that when there are multiple subjects, they may be the same or different.

[0017] In the present invention, the expression of chemical elements, unless otherwise specified, generally includes the concept of their isotopes. For example, the expression "hydrogen (H)" includes the concepts of its isotopes 1H (protium or H) and 2H (deuterium or D); carbon (C) includes 12C, 13C, etc., which will not be repeated.

[0018] The heteroatom in the heteroaryl group of the present invention generally refers to an atom or an atom group selected from N, O, S, P, Si and Se, preferably selected from N, O and S.

[0019] In the present specification, examples of halogen include fluorine, chlorine, bromine, and iodine.

[0020] The C1-C30 chain alkyl group is preferably a C1-C20 chain alkyl group, more preferably a C1-C10 chain alkyl group, and examples thereof include methyl, ethyl, n-propyl, n-butyl, n-hexyl, n-octyl, n-pentyl, n-heptyl, n-nonyl, and n-decyl groups.

[0021] The C3-C30 cycloalkyl group is preferably a C3-C20 cycloalkyl group, more preferably a C3-C10 cycloalkyl group, and examples thereof include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and adamantyl.

[0022] The present invention provides a method for synthesizing a key intermediate 2-aryl-2-(4-aminophenyl)propane. In a representative example, cheap and readily available aromatic alcohols can be used to synthesize the target intermediate with a purity of more than 99% and an overall yield of more than 50%.

[0023] Specifically, in order to synthesize 2-aryl-2-(4-aminophenyl)propane, the inventors selected arylphenol, which is easily available and inexpensive on the market, as a raw material. First, it reacted with trifluoromethanesulfonic anhydride to produce a trifluoromethanesulfonate. Then, the sulfonate reacted with benzophenone imine to complete carbon-nitrogen coupling (i.e., the construction of a C-N bond). Finally, the benzophenone was removed under acidic conditions to produce the target product. More specifically, as shown in the following figure:

[0024] The target compound structure of the present invention is:

[0025]

[0026] Wherein, Ar is one of a substituted or unsubstituted C6-C60 aryl group and a substituted or unsubstituted C3-C60 heteroaryl group, wherein the substituent is selected from a C1-C6 chain alkyl group, a C3-C10 cycloalkyl group, and a C1-C10 alkoxy group.

[0027] Preferably, Ar is one of the following groups which are substituted or unsubstituted by a C1-C6 aliphatic hydrocarbon group:

[0028] One of phenyl, naphthyl, biphenyl, terphenyl, pyridyl, quinolyl, phenanthrenyl, anthracenyl, furyl, thienyl, pyrrolyl, benzofuranyl, benzothienyl, and benzopyrrolyl;

[0029] The C1-C6 aliphatic hydrocarbon group as a substituent is an aliphatic group containing 1 to 6 carbon atoms, and may be a linear, branched, or cyclic hydrocarbon group, and may be a saturated or unsaturated group. Specific examples include methyl, ethyl, n-propyl, n-butyl, isopropyl, cyclopropyl, cyclobutyl, tert-butyl, pentyl, n-hexyl, and cyclohexyl.

[0030] Preferably, Ar includes but is not limited to the following structures:

[0031]

[0032] * is the position connected to the mother core, as the preferred target compound structure of the present invention:

[0033]

[0034] The synthetic method of the present invention comprises the following steps:

[0035] The first step is the synthesis step of intermediate M1', which is to contact cumene phenol with trifluoromethanesulfonic anhydride under alkaline conditions to obtain M1'.

[0036]

[0037] The second step is to synthesize the intermediate M2', wherein M1' is contacted with benzophenone imine and a palladium-containing catalyst under alkaline conditions to obtain M2'.

[0038]

[0039] The third step is the amination step, wherein M2' is contacted with an acid to obtain 2-phenyl-2-(4-aminophenyl)propane.

[0040]

[0041] Ar has the same meaning as described above.

[0042] Furthermore, the synthesis method of the preferred target compound of the present invention, 2-phenyl-2-(4-aminophenyl)propane, comprises the following steps:

[0043] S1, a step for synthesizing intermediate M1, a step for contacting cumene phenol with trifluoromethanesulfonic anhydride under alkaline conditions to obtain M1,

[0044]

[0045] S2. A step of synthesizing intermediate M2, comprising contacting M1 with benzophenone imine and a palladium-containing catalyst under alkaline conditions to obtain M2.

[0046]

[0047] S3. Amination step, contacting M2 with an acid to obtain 2-phenyl-2-(4-aminophenyl)propane.

[0048]

[0049] The primary innovation of the present invention lies in the design of the aforementioned synthetic route. To date, no method for synthesizing 2-aryl-2-(4-aminophenyl)propanes via this synthetic route has been described. While the synthesis steps of M1, M2, and the amination step described above are not entirely novel, the comprehensive application of these methods to achieve the desired product via a completely novel synthetic pathway is the inventors' primary contribution to the prior art.

[0050] As a representative synthesis method of the present invention, the inventors have conducted in-depth research on the synthesis method of 2-phenyl-2-(4-aminophenyl)propane. The synthesis methods of other 2-aryl-2-(4-aminophenyl)propanes are basically similar to this method and can be generalized.

[0051] Regarding the various synthesis steps of 2-phenyl-2-(4-aminophenyl)propane, in more detail, for step S1:

[0052] The operation of this step is not particularly limited, and any conventional method for reacting trifluoromethanesulfonic anhydride with a hydroxyl group can be used. The base in the reaction can be a conventional base for such reactions in the art, preferably an organic base, for example, one or more of triethylamine, pyridine, and 4-dimethylaminopyridine (DMAP). In the present invention, triethylamine is particularly preferably used.

[0053] This step is generally carried out in an organic solvent. The organic solvent may be a conventional organic solvent for this type of reaction in the art, and dichloromethane is particularly preferred in the present invention.

[0054] The amount of the organic solvent used can be any conventional amount used in this type of reaction in the art, as long as it does not affect the reaction. In the present invention, the preferred molar ratio of the organic solvent to cumene phenol is 0.1 L / mol to 5 L / mol, more preferably 0.2 L / mol to 0.5 L / mol. Generally, the molar ratio of the base to trifluoromethanesulfonic anhydride can be 1:1 to 3:1, preferably 1.4 to 1.6:1.

[0055] The reaction molar ratio of cumene phenol to trifluoromethanesulfonic anhydride is not particularly limited, but is generally 1:1 to 1:2, preferably 1:1 to 1.2.

[0056] The reaction temperature is a conventional temperature for this type of reaction in the art, preferably -50 to 0°C, particularly preferably -45 to -15°C.

[0057] In this step, preferably, after the cumene phenol, the base, and the organic solvent are mixed, the trifluoromethanesulfonate is added dropwise to the mixed system of the cumene phenol, the organic base, and the organic solvent; the mixing time of the mixed system is not specifically limited, and is generally 5 to 30 minutes, preferably 15 minutes.

[0058] After the reaction is completed, post-treatment such as concentration and / or filtration may be performed, and then purification by conventional column chromatography may be performed to obtain the product containing M1, and then proceed to step S2. Alternatively, step S2 may be performed directly without any treatment. Whether to perform post-treatment here can be determined by those skilled in the art as needed.

[0059] In step S2 of the present invention, M1 is contacted with benzophenone imine and a palladium-containing catalyst under alkaline conditions. This step is a key factor in the yield of the present invention. The most common method is to stir the reaction of M1 with benzophenone imine and a palladium-containing catalyst in a solvent. For the sake of catalyst activity, nitrogen protection can be preferably used, but it is not required.

[0060] As the palladium catalyst in step S2, a common palladium catalyst can be used, and for example, the following can be cited: [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium, palladium acetate, tris(dibenzylideneacetone)dipalladium-chloroform adduct, dichlorobis(tricyclohexylphosphine)palladium, di(cyanobenzene)dichloropalladium, tetrakis(triphenylphosphine)palladium, bis(acetonitrile)chloridepalladium(II), bistriphenylphosphinepalladiumdichloride, tris(dibenzylideneacetone)dipalladium, triphenylphosphine palladium acetate, di(tri-tert-butylphosphine)palladium, (1,5-cyclooctadiene)dichloropalladium(II), 1,2-bis(diphenylphosphino)ethanedichloropalladium(II), di(acetylacetone)palladium(I I), [1,3-bis(diphenylphosphinopropane)palladium chloride, allylpalladium(II) chloride dimer, palladium trifluoroacetate, bis(di-tert-butylphenylphosphine)palladium(II) dichloride, terpyridinium ruthenium chloride hexahydrate, 1,1,1,5,5,5-hexafluoroacetylacetonatepalladium(II), tris(dibenzylideneacetone)dipalladium, trans-dichlorobis(tri-O-tolylphosphine)palladium, 1,4-bis(diphenylphosphinobutane)dichloropalladium, bis(1,2-bis(diphenylphosphino)ethane)palladium, benzylbis(triphenylphosphine)palladium chloride, tri-tert-butylphosphinepalladium bromide, ammonium chloropalladate, trans-bis(triethylphosphine)palladium(II) dichloride, palladium tetraacetonitrile tetrafluoroborate, allyl chloride [ 1,3-Bis(2,6-diisopropylphenyl)imidazol-2-yl]palladium, dichlorodi-tert-butyl-(4-dimethylaminophenyl)phosphine palladium(II), allyl[1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene]palladium chloride, trans-bis-MU(M)-bis[2-(di-o-tolylphosphine)benzyl]acetate dipalladium(II), chloro-[2'-(dimethylamino)-2-biphenyl]-(dionobornylphosphine)-palladium, [(1,2,3-N)-3-phenyl-2-propenyl][1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-yl]palladium chloride, bis(diphenylphosphino)ferrocenepalladium dichloride , chloro[(1,2,3-)-3-phenyl-2-propenyl][1,3-bis(2,6-di-1-propylphenyl)imidazol-2-yl]palladium(II), chloride(di-2-norbornylphosphine)(2-dimethylaminomethylferrocen-1-yl)palladium(II), 1,3-bis(2,6-di-isopropylphenyl)imidazol-2-yl1,4-naphthoquinone)palladium dimer, 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene(1,4-naphthoquinone)palladium(0) dimer, allylchlorido[1,3-bis(2,6-di-isopropylphenyl)-4,5-dihydroimidazol-2-yl]palladium, tris(dibenzylideneacetone)dipalladium.

[0061] Preferred examples include tetrakis(triphenylphosphine)palladium, palladium acetate, bis(diphenylphosphinoferrocenedichloropalladium) and bis(dibenzylideneacetone)palladium. Among them, bis(diphenylphosphinoferrocenedichloropalladium) is particularly preferred.

[0062] In step S2 of the present invention, the solvent may be a conventional organic solvent. As the organic solvent, for example, at least one organic solvent selected from the following group may be cited: toluene, xylene, dichlorobenzene, DMF, dioxane, tetrahydrofuran, wherein DMF is N,N-dimethylformamide, CAS 68-12-2).

[0063] The base in step S2 is not particularly limited. For better reaction yield, the preferred base can be alkali metal methoxide, alkali metal hydroxide, alkali metal carbonate, or alkali metal tert-butoxide. Among them, the base is more preferably sodium methoxide and / or sodium tert-butoxide.

[0064] In this reaction, the amount of the organic solvent used can be any conventional amount used in this type of reaction in the art, as long as it does not affect the reaction. In the present invention, the volume molar ratio of the organic solvent to M1 is particularly preferably 0.1L / mol to 5L / mol; more preferably 0.2L / mol to 0.5L / mol. Generally speaking, the molar ratio of the base to benzophenone imine can be 1:1 to 5:1; more preferably 1.3 to 1.6:1, and most preferably 1.5:1.

[0065] The reaction molar ratio of M1 to the palladium-containing catalyst is not particularly limited, but is generally 1:0.1 to 1:0.02; preferably 1:0.04 to 0.06.

[0066] The reaction temperature is conventional in the art for this type of reaction, and in the present invention, it is preferably 40-100°C, more preferably 75-85°C, and particularly preferably 79-81°C.

[0067] In this reaction step, when the reaction is carried out in a solvent, a phosphine ligand can be added to assist the reaction, but it is not necessary. As the added ligand, the most commonly used in the art is a bidentate ligand, such as BINAP, which is 1,1'-binaphthyl-2,2'-bisdiphenylphosphine, CAS 98327-87-8. The present invention follows the conventional method of using BINAP in the art and conducts various optimization explorations such as solvents, acids and bases, but almost no improvement in yield and recovery rate is achieved. For the substrate of the present invention, the bidentate ligand hardly changes the reaction efficiency.

[0068] However, the inventors unexpectedly discovered that uncommon phosphine ligands, and even some monodentate ligands, are more effective in promoting the reaction. Preferred monodentate phosphine ligands are selected from the following group: S-Phos and X-Phos. Ferrocene and Xant-Phos were also found to be very effective. It remains difficult to explain why individual ligands improve reaction efficiency. S-Phos is 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl, CAS number 657408-07-6; X-Phos is 2-dicyclohexylphosphino-2,4,6-triisopropylbiphenyl, CAS number 564483-18-7; and Xant-Phos is 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, CAS number 161265-03-8.

[0069] It can be seen that another important innovation of the present invention is that the inventors have accidentally discovered that a specific combination of ligands and catalysts can increase the conversion rate of the reaction to an astonishing degree. Specifically;

[0070] Of all the catalytic systems, only [1,1'-bis(diphenylphosphino)ferrocene] (sometimes counted as Pd(dppf)Cl2) and tris(dibenzylideneacetone)dipalladium (sometimes counted as Pd2(dba)3) appear to be catalytic when combined with X-Phos or S-Phos:

[0071]

[0072] In addition, only when sodium methoxide is used as a base to participate in the reaction, the reaction conversion rate can reach more than 30%;

[0073]

[0074] Moreover, when toluene is used as the solvent and S-Phos is used as the ligand, the reaction can be carried out at 80° C., and the conversion rate can reach more than 80% (as shown in Table 1).

[0075]

[0076] After the reaction is completed, the product can be concentrated and / or filtered, and then purified by conventional column chromatography before proceeding to the next reaction. However, since impurities do not affect the next reaction, the reaction system can also be directly subjected to the next reaction without purification.

[0077] Among them, Pd(dppf)Cl2 is 1,1'-bis(diphenylphosphino)ferrocenepalladium(II) dichloride, CAS number is 72287-26-4); Pd2(dba)3 is tris(dibenzylideneacetone)dipalladium, CAS number is 60748-47-2.

[0078] In the amination step S3, 2-phenyl-2-(4-aminophenyl)propane can be obtained by contacting M2 with an acid. The acid used in S3 can be a commonly used acid, such as hydrochloric acid or sulfuric acid. Strong oxidizing acids are not recommended because they may result in a decrease in yield. A preferred acid is hydrochloric acid, specifically 0.5 to 10.4 mol / L.

[0079] The reaction can be carried out by directly adding the product obtained from the previous step to the acid solution. The molar ratio of M2 to the acid is not particularly limited. When hydrochloric acid is used, the molar ratio of M2 to hydrochloric acid is preferably 1:1 to 1:50, and more preferably 1:5 to 1:10.

[0080] The reaction can be carried out at room temperature or by heating, and is preferably carried out at 50 to 70°C.

[0081] After the reaction is completed, the product can be obtained by recrystallization in the form of the acid salt used. The acid salt of the target product can be used directly as an intermediate.

[0082] The present invention provides a novel synthesis route for 2-phenyl-2-(4-aminophenyl)propane using inexpensive cumene phenol as a raw material, employing novel techniques and a specific process design. The experimental procedures of the present invention are simple and suitable for scale-up. Regarding the specific method for synthesizing 2-phenyl-2-(4-aminophenyl)propane, a compound most commonly used in the art, in a further preferred embodiment of the present invention, the synthesis method for 2-phenyl-2-(4-aminophenyl)propane (hydrochloride) achieves an overall yield of greater than 50%.

[0083] Based on a method similar to the synthesis of 2-phenyl-2(4-aminophenyl)propane (hydrochloride) described above, 2-aryl-2(4-aminophenyl)propane, an intermediate that is difficult to prepare and purchase, can be widely used in the synthesis of OLED materials, which is of great significance. For example, by replacing the above-mentioned Ar, the present invention can also conveniently synthesize the following types of other 2-aryl-2(4-aminophenyl) compounds:

[0084] For example, when Ar is a pyridyl group, the process can be briefly represented as follows:

[0085]

[0086] For example, when Ar is tolyl, the process can be briefly expressed as follows:

[0087]

[0088] For example, when Ar is naphthyl, the process can be simply represented as follows:

[0089]

[0090] For example, when Ar is a terphenyl group, the process can be simply represented as follows:

[0091]

[0092] For example, when Ar is a benzothiophenyl group, the process can be simply represented as follows: BRIEF DESCRIPTION OF THE DRAWINGS

[0093] Figure 1 This is the mass spectrum of intermediate M1 in the synthesis method of 2-phenyl-2(4-aminophenyl)propane.

[0094] Figure 2 This is the mass spectrum of the intermediate M2 in the synthesis method of 2-phenyl-2(4-aminophenyl)propane.

[0095] Figure 3 This is the mass spectrum of the target product in the synthesis method of 2-phenyl-2(4-aminophenyl)propane.

[0096] Figure 4 This is the H-NMR spectrum of the target product in the synthesis method of 2-phenyl-2(4-aminophenyl)propane. DETAILED DESCRIPTION

[0097] Synthesis Example 1:

[0098] Synthesis of intermediate M1

[0099]

[0100] Experimental operation: cumene phenol (30g, 141.31mmol) and triethylamine (21.45g, 211.97mmol) were dissolved in 500ml of dichloromethane. Under low temperature conditions (-40°C), trifluoromethanesulfonate (47.84g, 169.58mmol) was dissolved in 300ml of dichloromethane and slowly added dropwise to the reaction system to ensure that the system temperature did not exceed -20°C. After the addition was completed, the reaction was carried out at room temperature for 0.5h. After GC-MS test, the raw material reaction was complete, 500ml of saturated ammonium chloride aqueous solution was added, the liquid was washed, washed three times with water and then dried. After decompression drying, column chromatography was purified to obtain 45g of the target product with a yield of 92.5%.

[0101] Synthesis of intermediate M2

[0102]

[0103] The catalyst Pd(dppf)Cl2 (0.64 g, 0.87 mmol), S-Phos (2.68 g, 6.53 mmol), and sodium methoxide (1.57 g, 29.04 mmol) were added to a 1 L single-necked bottle, 100 ml of toluene was added, and nitrogen was blown for 10 minutes. Then, the intermediate M1 and diphenyl ketone imine were added, and the reaction was carried out at 80°C under nitrogen protection for 10 hours (diphenyl ketone imine contains benzophenone impurities).

[0104] The next day, samples were taken for GC-MS testing. The raw materials reacted completely, mainly the target product, with a conversion rate of 89%. The reaction system was filtered and no separate purification was required, waiting for the next experiment.

[0105] Synthesis of target product

[0106]

[0107] Experimental operation: Add about 50 ml of concentrated hydrochloric acid to the reaction system in the previous step (after filtration), heat and stir the reaction at 60°C for 10 hours, then take a sample for GC-MS detection. The intermediate M2 reacts completely, and the reaction system is concentrated to dryness under reduced pressure. It is washed four times with 200 ml*4 of petroleum ether, and then recrystallized once with ethanol + toluene to obtain 11.82 g of the product, and the HPLC test is 99.3% (the target product exists in the form of hydrochloride).

[0108] Mass spectrometry data of M1, M2 and target product can be found in Figures 1 to 3 According to the specific feeding conditions, it can be determined that the synthesis of M1, M2 and the target product is successful. Further NMR spectrum of the target product is shown in Figure 4 , which is consistent with the situation.

[0109] Synthesis Examples 2 to 38:

[0110] Except that in step S2, the synthesis reaction conditions of M2 were replaced according to the data listed in Table 1, the same experiment as in the synthesis example was carried out to obtain the target product.

[0111] Table 1

[0112]

[0113] Synthesis Examples 39 to 43: Synthesis of Compounds Substituted with Ar

[0114] Synthesis Example 39:

[0115] Synthesis of intermediate M3

[0116]

[0117] Experimental operation: 4-(3-pyridyl)isopropylphenol (30 g, 141.31 mmol) and triethylamine (21.45 g, 211.97 mmol) were dissolved in 500 ml of dichloromethane. Under low temperature conditions (-40°C), trifluoromethanesulfonate (47.84 g, 169.58 mmol) was dissolved in 300 ml of dichloromethane and slowly added dropwise to the reaction system to ensure that the system temperature did not exceed -20°C. After the addition was completed, the reaction was carried out at room temperature for 0.5 h. After GC-MS test, the raw material reaction was complete, and 500 ml of saturated ammonium chloride aqueous solution was added, the separated liquid was washed with water three times and then dried. After decompression drying, column chromatography was purified to obtain 43 g of the target product with a yield of 90.1%.

[0118] Synthesis of intermediate M4

[0119]

[0120] The catalyst Pd(dppf)Cl2 (0.64 g, 0.87 mmol), S-Phos (3.68 g, 6.53 mmol), and sodium methoxide (1.57 g, 29.04 mmol) were added to a 1 L single-necked bottle, 100 ml of toluene was added, and nitrogen was blown for 10 minutes. Then, the intermediate M1 and diphenyl ketone imine were added, and the reaction was carried out at 80°C under nitrogen protection for 10 hours (diphenyl ketone imine contains benzophenone impurities).

[0121] The next day, samples were taken for GC-MS testing. The raw materials reacted completely, mainly the target product, with a conversion rate of 95%. The reaction system was filtered and no separate purification was required, waiting for the next experiment.

[0122] Synthesis of target product

[0123]

[0124] Experimental procedure: Add about 50 ml of concentrated hydrochloric acid to the reaction system in the previous step (after filtration), heat and stir the reaction at 60°C for 10 hours, then take a sample for GC-MS detection. The reaction of intermediate M4 is complete. The reaction system is concentrated to dryness under reduced pressure, washed four times with 200 ml*4 of petroleum ether, and then recrystallized once with ethanol + toluene to obtain 12.11 g of the product, and the HPLC test is 99.6% (the target product exists in the form of hydrochloride).

[0125] MS:212.30; 1 HNMR (CDCl3): 1.69 (s, 6H), 4.91 (s, 2H), 6.44 (d, 2H), 7.03 (d, 2H), 7.24 (m, 1H), 7.67 (m, 1H), 8.35 (m, 1H), 8.41 (s, 1H).

[0126] Synthesis Example 40:

[0127] Synthesis of intermediate M5

[0128]

[0129] Experimental operation: 4-(3-methylphenyl)isopropylphenol (30 g, 132.56 mmol) and triethylamine (20.12 g, 198.83 mmol) were dissolved in 500 ml of dichloromethane. Under low temperature conditions (-40°C), trifluoromethanesulfonate (44.88 g, 159.07 mmol) was dissolved in 300 ml of dichloromethane and slowly added dropwise to the reaction system to ensure that the system temperature did not exceed -20°C. After the addition was completed, the reaction was carried out at room temperature for 0.5 h. After GC-MS test, the raw material reaction was complete, and 500 ml of saturated ammonium chloride aqueous solution was added, the liquid was washed, washed three times with water and then dried. After decompression drying, column chromatography was purified to obtain 43 g of the target product with a yield of 91.4%.

[0130] Synthesis of intermediate M6

[0131]

[0132] The catalyst Pd(dppf)Cl2 (0.61 g, 0.84 mmol), S-Phos (2.58 g, 6.28 mmol), and sodium methoxide (3.39 g, 62.38 mmol) were added to a 1 L single-necked bottle, 500 ml of toluene was added, and nitrogen was blown for 10 minutes. Then, the intermediate M6 and diphenyl ketone imine were added, and the reaction was carried out at 80°C under nitrogen protection for 10 hours (diphenyl ketone imine contains benzophenone impurities).

[0133] The next day, samples were taken for GC-MS testing. The raw materials reacted completely, mainly the target product, with a conversion rate of 89%. The reaction system was filtered and no separate purification was required, waiting for the next experiment.

[0134] Synthesis of target product

[0135]

[0136] Experimental operation: Add about 50 ml of concentrated hydrochloric acid to the reaction system in the previous step (after filtration), heat and stir the reaction at 60°C for 10 hours, then take a sample for GC-MS detection. The intermediate M6 reacts completely, and the reaction system is concentrated to dryness under reduced pressure. It is washed four times with 200 ml*4 of petroleum ether, and then recrystallized once with ethanol + toluene to obtain 10.56 g of the product, and the HPLC test shows 98.8% (the target product exists in the form of hydrochloride).

[0137] MS:225.30; 1HNMR (CDCl3): 1.69 (s, 6H), 2.31 (s, 3H), 4.91 (s, 2H), 6.44 (d, 2H), 6.89 (m, 1H), 7.03 (d, 2H), 7.09 (m, 2H), 7.47 (m, 1H).

[0138] Synthesis Example 41:

[0139] Synthesis of intermediate M7

[0140]

[0141] Experimental operation: 4-(2-naphthyl)isopropylphenol (30 g, 114.35 mmol) and triethylamine (17.36 g, 171.53 mmol) were dissolved in 500 ml of dichloromethane. Under low temperature conditions (-40°C), trifluoromethanesulfonate (38.71 g, 137.22 mmol) was dissolved in 300 ml of dichloromethane and slowly added dropwise to the reaction system to ensure that the system temperature did not exceed -20°C. After the addition was completed, the reaction was carried out at room temperature for 0.5 h. After GC-MS test, the raw material reaction was complete, and 500 ml of saturated ammonium chloride aqueous solution was added to wash the separated liquid, washed three times with water and dried. After decompression drying, column chromatography was purified to obtain 44 g of the target product with a yield of 97.4%.

[0142] Synthesis of intermediate M8

[0143]

[0144] The catalyst Pd(dppf)Cl2 (0.56 g, 0.76 mmol), S-Phos (2.34 g, 5.7 mmol), and sodium methoxide (3.08 g, 57.05 mmol) were added to a 1 L single-necked bottle, 100 ml of toluene was added, and nitrogen was blown for 10 minutes. Then, the intermediate M7 and diphenyl ketone imine were added, and the reaction was carried out at 80 ° C for 10 hours under nitrogen protection (diphenyl ketone imine contains benzophenone impurities).

[0145] The next day, samples were taken for GC-MS testing. The raw materials reacted completely, mainly the target product, with a conversion rate of 96%. The reaction system was filtered and no separate purification was required, waiting for the next experiment.

[0146] Synthesis of target product

[0147]

[0148] Experimental operation: Add about 50 ml of concentrated hydrochloric acid to the reaction system in the previous step (after filtration), heat and stir the reaction at 60°C for 10 hours, then take a sample for GC-MS detection. The intermediate M2 reacts completely, and the reaction system is concentrated to dryness under reduced pressure. It is washed four times with 200 ml*4 of petroleum ether, and then recrystallized once with ethanol + toluene to obtain 10.54 g of the product, and the HPLC test is 99.5% (the target product exists in the form of hydrochloride).

[0149] MS:261.40; 1 HNMR (CDCl3): 1.75 (s, 6H), 4.91 (s, 2H), 6.44 (d, 2H), 7.03 (d, 2H), 7.48 (m, 3H), 7.60 (s, 1H), 7.92 (m, 3H).

[0150] Synthesis Example 42:

[0151] Synthesis of intermediate M9

[0152]

[0153] Experimental operation: 4-[(3,5-diphenyl)phenyl]isopropylphenol (30 g, 82.31 mmol) and triethylamine (12.49 g, 123.46 mmol) were dissolved in 500 ml of dichloromethane. Under low temperature conditions (-40°C), trifluoromethanesulfonate (27.84 g, 98.77 mmol) was dissolved in 300 ml of dichloromethane and slowly added dropwise to the reaction system to ensure that the system temperature did not exceed -20°C. After the addition was completed, the reaction was carried out at room temperature for 0.5 h. After GC-MS test, the raw material reaction was complete, 500 ml of saturated ammonium chloride aqueous solution was added, the liquid was washed, washed three times with water and then dried. After decompression drying, column chromatography was purified to obtain 36 g of the target product with a yield of 89.9%.

[0154] Synthesis of intermediate M10

[0155]

[0156] The catalyst Pd(dppf)Cl2 (0.44 g, 0.60 mmol), S-Phos (1.86 g, 4.53 mmol), and sodium methoxide (2.45 g, 45.31 mmol) were added to a 1 L single-necked bottle, 100 ml of toluene was added, and nitrogen was blown for 10 minutes. Then, the intermediate M1 and diphenyl ketone imine were added, and the reaction was carried out at 80°C under nitrogen protection for 10 hours (diphenyl ketone imine contains benzophenone impurities).

[0157] The next day, samples were taken for GC-MS testing. The raw materials reacted completely, mainly the target product, with a conversion rate of 95%. The reaction system was filtered and no separate purification was required, waiting for the next experiment.

[0158] Synthesis of target product

[0159]

[0160] Experimental operation: About 50 ml of concentrated hydrochloric acid was added to the reaction system in the previous step (after filtration), and the reaction was heated and stirred at 60°C for 10 hours. Then a sample was taken for GC-MS detection. The intermediate M10 was completely reacted. The reaction system was concentrated to dryness under reduced pressure, washed four times with 200 ml*4 of petroleum ether, and then recrystallized once with ethanol + toluene to obtain 12.56 g of the product, and the HPLC test showed 99.3% (the target product existed in the form of hydrochloride).

[0161] MS:363.50; 1 HNMR (CDCl3): 1.69 (s, 6H), 4.91 (s, 2H), 6.44 (d, 2H), 7.03 (d, 2H), 7.41 (m, 2H), 7.49 (m, 4H), 7.75 (m, 4H), 7.84 (s, 1H).

[0162] Synthesis Example 43:

[0163] Synthesis of intermediate M11

[0164]

[0165] Experimental operation: 4-(2-Benzothiphenyl)phenol (30 g, 111.78 mmol) and triethylamine (16.79 g, 167.68 mmol) were dissolved in 500 ml of dichloromethane. Under low temperature conditions (-40°C), trifluoromethanesulfonate (37.84 g, 134.14 mmol) was dissolved in 300 ml of dichloromethane and slowly added dropwise to the reaction system to ensure that the system temperature did not exceed -20°C. After the addition was completed, the reaction was carried out at room temperature for 0.5 h. After GC-MS test, the raw material reaction was complete, 500 ml of saturated ammonium chloride aqueous solution was added, the separated liquid was washed with water three times and then dried. After decompression drying, column chromatography was purified to obtain 39 g of the target product with a yield of 96.5%.

[0166] Synthesis of intermediate M12

[0167]

[0168] The catalyst Pd(dppf)Cl2 (0.55 g, 0.75 mmol), S-Phos (2.31 g, 5.62 mmol), and sodium methoxide (3.04 g, 56.19 mmol) were added to a 1 L single-necked bottle, 100 ml of toluene was added, and nitrogen was blown for 10 minutes. Then, the intermediate M1 and diphenyl ketone imine were added, and the reaction was carried out at 80°C under nitrogen protection for 10 hours (diphenyl ketone imine contains benzophenone impurities).

[0169] The next day, samples were taken for GC-MS testing. The raw materials reacted completely, mainly the target product, with a conversion rate of 95%. The reaction system was filtered and no separate purification was required, waiting for the next experiment.

[0170] Synthesis of target product

[0171]

[0172] Experimental operation: Add about 50 ml of concentrated hydrochloric acid to the reaction system in the previous step (after filtration), heat and stir the reaction at 60°C for 10 hours, then take a sample for GC-MS detection. The intermediate M2 reacts completely, and the reaction system is concentrated to dryness under reduced pressure. It is washed four times with 200 ml*4 of petroleum ether, and then recrystallized once with ethanol + toluene to obtain 10.81 g of the product, and the HPLC test is 99.1% (the target product exists in the form of hydrochloride).

[0173] MS:267.4; 1 HNMR (CDCl3): 1.72 (s, 6H), 4.91 (s, 2H), 6.44 (d, 2H), 7.03 (d, 2H), 7.32 (m, 1H), 7.40 (s, 1H), 7.49 (m, 1H), 7.79 (m, 1H), 7.93 (m, 1H).

[0174] Conclusion: The present invention provides a method for synthesizing 2-aryl-2(4-aminophenyl)propane, a key intermediate for synthesizing optoelectronic materials, in particular a method for synthesizing common 2-phenyl-2(4-aminophenyl)propane.

[0175] After extensive experiments, a method was found that uses cheap aromatic phenol (for 2-phenyl-2(4-aminophenyl)propane, it is cumenephenol) as raw material. Through a catalytic coupling reaction (an optimized catalytic system was found), a high-yield conversion of hydroxyl groups to amino groups (>80%) was achieved, with an overall yield of over 50%. Moreover, the operation is simple and easy, the cost is low, and it is suitable for industrial scale-up production.

[0176] Finally, it should be noted that the embodiments described above are only used to illustrate the technical solutions of the present invention, rather than to limit them. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that the technical solutions described in the aforementioned embodiments can still be modified, or some or all of the technical features therein can be replaced by equivalents. However, these modifications or replacements do not deviate from the essence of the corresponding technical solutions within the scope of the technical solutions of the various embodiments of the present invention. All publications and patent documents cited in this specification are incorporated herein by reference, as if each publication or patent was specifically indicated to be incorporated herein by reference. Various changes and equivalents may be made to the various embodiments disclosed in this application without departing from the essence and scope of the present application. Unless otherwise indicated in the context, any feature, step or embodiment of the embodiments of the present disclosure may be used in combination with any other feature, step or embodiment.

Claims

1. A method for synthesizing 2-aryl-2-(4-aminophenyl)propane represented by formula (A), in, Ar is a substituted or unsubstituted C6-C60 aryl group, a substituted or unsubstituted C3-C60 heteroaryl group, wherein the substituent is selected from a C1-C6 chain alkyl group, a C3-C10 cycloalkyl group, a C1-C10 alkoxy group, It includes the following steps: Step S1a is a step for synthesizing intermediate M1', which involves contacting cumene phenol with trifluoromethanesulfonic anhydride under alkaline conditions to obtain M1'. Step S2a. The synthesis step of the intermediate M2 ', M1 ', is contacted with benzophenone imine and a palladium-containing catalyst under basic conditions to obtain M2 'step, The palladium-containing catalyst is selected from [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride and bis(dibenzylideneacetone)palladium; the ligand is selected from X-Phos and S-Phos; the base is at least one selected from the following group: alkali metal methoxide, alkali metal hydroxide, alkali metal carbonate, alkali metal phosphate or alkali metal tert-butoxide; toluene is used as solvent and the reaction is carried out at 80-100°C. S3a step amination step, M2 'contact with an acid to obtain 2-phenyl-2- (4-aminophenyl) propane, Ar has the same meaning as described above.

2. The synthesis method according to claim 1, wherein Ar is one of the following groups which are substituted or unsubstituted by a C1-C6 aliphatic hydrocarbon group: One of phenyl, naphthyl, biphenyl, terphenyl, pyridyl, quinolyl, phenanthryl, anthracenyl, furyl, thienyl, pyrrolyl, benzofuranyl, benzothienyl, and benzopyrrolyl.

3. The synthesis method according to claim 1, wherein Ar is the following structure: * indicates the position of connection with the mother nucleus.

4. The synthesis method according to claim 1, wherein Ar is a benzene ring, which comprises the following steps: S1a. A step for synthesizing intermediate M1, comprising contacting cumene phenol with trifluoromethanesulfonic anhydride under alkaline conditions to obtain M1. S2a. A step for synthesizing intermediate M2, comprising contacting M1 with benzophenone imine and a palladium-containing catalyst under alkaline conditions to obtain M2. S3a. Amination step, contacting M2 with an acid to obtain 2-phenyl-2-(4-aminophenyl)propane 5. The synthesis method according to claim 1 or 4, wherein The base in step S1a is triethylamine, and the acid used in step S3a is hydrochloric acid.

6. The synthesis method according to claim 1 or 4, wherein In step S3a, the chemical reaction is carried out at 50-70°C.

7. The synthesis method according to claim 6, wherein The base is sodium methoxide and / or sodium tert-butoxide.

8. The synthesis method according to claim 7, wherein The base is sodium methoxide.

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