A method for synthesizing dibenzyl-alpha,alpha-diphenylamine compounds

Abstract

The application discloses a method for synthesizing dibenzyl-alpha,alpha-diphenylamine compounds, and belongs to the technical field of organic synthesis. The method uses aromatic dialdehyde, 2-cyclohexenone and benzylamine as raw materials, and carries out a heating reaction in an organic solvent in the presence of titanium tetrachloride. After the reaction is completed, an N,N'-dibenzyl-substituted dibenzyl-alpha,alpha-diphenylamine intermediate is separated and purified. The intermediate is subjected to hydrogenation and debenzylization by using Pd-C / H2, and after separation and purification, the dibenzyl-alpha,alpha-diphenylamine compound is obtained. The preparation process is mild and simple, and the problems of low chemical selectivity and low regioselectivity in traditional synthesis are avoided. In addition, the aryl compatibility of the aromatic dialdehyde is good, and the atomic economy is high, thereby providing raw material support for new drug screening and monomer synthesis of organic functional materials.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, specifically to a method for synthesizing dibenzyl-α,α-diphenylamine compounds. Background Technology

[0002] α-Benzylaniline is an important class of aromatic amine derivatives, with its skeleton widely found in many natural products and synthetic drugs. For example, miansheline is a potent tetracyclic antidepressant that exerts its therapeutic effect by blocking α-adrenergic receptors. Midazolam, a benzodiazepine, produces a sedative effect by inhibiting the neurotransmitter γ-aminobutyric acid (GABA) and is clinically used to treat insomnia. In the petrochemical industry, these compounds can be used as highly effective antioxidant additives. When a dibenzyl group is used as a connecting bridge to link two molecules of aniline at their ortho positions, dibenzyl-α,α-diphenylamine is obtained. These compounds retain the chemical transformation properties of α-benzylaniline, and the increased number of reaction sites in the molecule facilitates the efficient construction of various functional molecules. For example, the complete substitution of the diamino group with an NCO group can be used to produce polyurethane; dibenzylphenol, obtained through chemical transformation of the diamino group, has activity in inhibiting melanin production; furthermore, biphenylyl aromatic derivatives obtained by oxidation of the dibenzyl position serve as important synthetic intermediates with broad application prospects in dyes, pharmaceuticals, and other fields.

[0003] Traditional α-benzyl substitution of aniline is often achieved through Friedel-Crafts reactions of benzyl halides with aniline. However, this aromatic electrophilic substitution reaction exhibits poor chemoselectivity and regioselectivity, making it difficult to control the amount and position of the added benzyl group. When using dibenzyl halides as bisbenzyl reagents to synthesize dibenzyl-α,α-diphenylamine, the reaction pathway becomes even more complex, and the product faces the challenge of isomer separation. Cross-coupling of transition metal-catalyzed benzyl reagents with aniline derivatives has also proven to be an effective strategy. These synthetic methods require the aniline unit and the prefunctionalized benzyl reagent, adding extra reaction steps and costs, which contradicts the principles of green chemistry. In 2005, Strauss's group reported a synthesis of the N,N'-dibenzyl-substituted product of 1,3-dibenzyl-α,α-diphenylamine using isophthalaldehyde, 2-cyclohexenone, and benzylamine as reactants, with a yield of 65% (Organic Letters, 2005, 7, 1525–1528). However, the catalytic system used to achieve this conversion is relatively complex and requires co-catalysis by benzoic acid and triethylenediamine.

[0004] In summary, existing methods for synthesizing dibenzyl-α,α-diphenylamine suffer from drawbacks such as cumbersome routes, poor atom economy, limited applicability, and unsatisfactory yields. Therefore, it is essential to explore more efficient, convenient, and environmentally friendly methods for synthesizing dibenzyl-α,α-diphenylamine compounds. Summary of the Invention

[0005] To address the problems of cumbersome synthetic routes, low yields, and insufficient universality in the synthesis of dibenzyl-α,α-diphenylamine, this invention provides a method for synthesizing dibenzyl-α,α-diphenylamine compounds, specifically comprising the following steps: (1) Using aromatic dialdehyde, 2-cyclohexenone and benzylamine as raw materials, the reaction was carried out in an organic solvent under the catalysis of titanium tetrachloride; after the reaction was completed, the intermediate shown in Formula II was obtained by separation and purification.

[0006] (2) The intermediate shown in Formula II was hydrogenated and debenzylated under Pd-C and H2 conditions, and then purified to obtain dibenzyl-α,α-diphenylamine compounds as shown in Formula I.

[0007] The aromatic dialdehyde has any one of the following structural formulas: , , , , , ; The structural formula of the 2-cyclohexenone is: ; The structural formula of the benzylamine is: ; The structural formula of formula II is: ; The structural formula of Formula I is: ; In Formula II and Formula I, the Ar group is one of the following structures: , , , , and .

[0008] Preferably, in step (1) of the present invention, the molar ratio of aromatic dialdehyde, 2-cyclohexenone, and benzylamine is 1:3:2.5.

[0009] Preferably, the molar ratio of aromatic dialdehyde and titanium tetrachloride in step (1) of the present invention is 1:1.

[0010] Preferably, the organic solvent in step (1) of the present invention is one of toluene, 1,1,2,2-tetrachloroethane, 1,4-dioxane, and acetonitrile.

[0011] Preferably, in step (1) of the present invention, the concentration of aromatic dialdehyde in the organic solvent is 1 mol / L.

[0012] Preferably, the heating reaction conditions in step (1) of the present invention are: 80~110°C. o C reaction for 3 hours.

[0013] Preferably, in step (2) of the present invention, the hydrogenation debenzylation is carried out on the intermediate shown in Formula II under Pd-C and H2 conditions. Specifically, the intermediate, acetic acid and organic solvent are mixed, Pd-C is added, H2 is introduced and reacted at room temperature for 6 hours. After the reaction is completed, the pH of the reaction solution is adjusted to 9-10, Pd-C is removed by filtration and the mixture is separated and purified.

[0014] Preferably, the Pd-C of the present invention is a Pd-C catalyst with a Pd metal loading of 10% by mass, wherein the mass of palladium accounts for 10% of the total mass of the Pd-C catalyst.

[0015] Preferably, the molar ratio of the intermediate to acetic acid in this invention is 1:0.2; the amount of Pd-C used is 10% of the mass of the intermediate; and the concentration of the intermediate in the organic solvent is 0.5 mol / L.

[0016] Preferably, the organic solvent of the present invention is one of dichloromethane, tetrahydrofuran, methanol, ethanol, and toluene.

[0017] Unless otherwise specified, all reagents used in this invention are commercially available analytical grade reagents.

[0018] This invention provides a method for synthesizing dibenzyl-α,α-diphenylamine compounds, which has the following beneficial effects: (1) The present invention uses aromatic dialdehyde, 2-cyclohexenone and benzylamine as raw materials, and reacts them in the presence of inexpensive and readily available titanium tetrachloride to complete the construction of the diphenylamine unit in the molecular structure and the benzyl substitution at the ortho position of aniline in one step. Then, through an easily implemented hydrogenation operation, dibenzyl-α,α-diphenylamine compounds are obtained.

[0019] (2) The reaction conditions of this invention are mild and the process is simple. It eliminates the complicated raw material preparation steps required by traditional synthesis strategies and avoids the common problems of low chemical selectivity and regioselectivity.

[0020] (3) The present invention has good aryl compatibility with aromatic dialdehydes and high atom economy, providing raw material support for new drug screening and the synthesis of monomers for organic functional materials. Attached Figure Description

[0021] Figure 1 This is the hydrogen nuclear magnetic resonance spectrum of compound I-1 prepared in Example 1 of this invention.

[0022] Figure 2 This is the hydrogen nuclear magnetic resonance spectrum of compound I-2 prepared in Example 2 of this invention.

[0023] Figure 3 This is the hydrogen nuclear magnetic resonance spectrum of compound I-3 prepared in Example 3 of this invention.

[0024] Figure 4 This is the hydrogen nuclear magnetic resonance spectrum of compound I-4 prepared in Example 4 of this invention.

[0025] Figure 5 This is the hydrogen nuclear magnetic resonance spectrum of compound I-5 prepared in Example 5 of this invention.

[0026] Figure 6 This is the hydrogen nuclear magnetic resonance spectrum of compound I-6 prepared in Example 6 of this invention. Detailed Implementation

[0027] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0028] The 10% Pd-C used in the embodiments of the present invention refers to a Pd-C catalyst with a Pd metal loading of 10% by mass, wherein the mass of palladium accounts for 10% of the total mass of the catalyst (the sum of the mass of palladium and the activated carbon support).

[0029] Example 1 A method for synthesizing dibenzyl-α,α-diphenylamine compounds, the reaction equation of which is as follows: The specific experimental steps are as follows: (1) Mix isophthalaldehyde (6.8 g, 50.6 mmol), benzylamine (11.1 mL, 101.2 mmol), and toluene (51 mL), and add titanium tetrachloride (5.6 mL, 50.6 mmol). Heat at 110 °C o The reaction mixture was heated at C for 15 min. Then, 2-cyclohexenone (9.8 mL, 101.2 mmol) and benzylamine (2.8 mL, 25.3 mmol) were added to the reaction solution. After reacting for 1 h, 4.9 mL of 2-cyclohexenone (50.6 mmol) was added, and the reaction was continued at 110 °C. o After reacting for 2 hours, the reaction was stopped and cooled to room temperature. The mixture was poured into ice water and the organic phase toluene layer was extracted and separated. The organic phase was then washed twice with water, dried with anhydrous Na2SO4, and the solvent was removed by concentration under reduced pressure. The residue was purified by silica gel column chromatography to obtain a white solid, which was 16.1 g of intermediate II-1, with a yield of 68%.

[0030] The NMR spectrum data of intermediate II-1 are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.26-7.17 (m, 7H), 7.14-7.08 (m, 6H), 7.02-6.99 (m, 5H), 6.70-6.66 (m, 2H), 6.58 (d, J = 8.0 Hz, 2H), 4.18 (s, 4H), 3.89-3.87 (m, 2H), 3.82 (s, 4H).

[0031] 13 C NMR (100 MHz, CDCl3) δ 146.0, 139.9, 139.4, 130.6, 129.2, 129.1,128.7, 128.0, 127.3, 127.8, 126.8, 124.7, 117.3, 111.0, 48.1, 38.2.

[0032] (2) Intermediate II-1 (16.1 g, 34.4 mmol), acetic acid (0.4 mL, 6.9 mmol) and dichloromethane (69 mL) were mixed, and 10% Pd-C (1.6 g, 10 wt%) was added. H2 was introduced and the reaction was carried out at room temperature and pressure for 6 h. After the reaction was completed, the pH of the reaction solution was adjusted to about 9.5 with a 5 mol / L sodium hydroxide aqueous solution. Pd-C was removed by filtration, the organic phase was separated, the organic phase was dried with anhydrous Na2SO4, the solvent was removed by vacuum concentration, and the residue was recrystallized with petroleum ether and ethyl acetate to obtain 9.4 g of grayish-white solid compound I-1 with a yield of 95%.

[0033] The NMR spectrum data of compound I-1 are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.23-7.20 (m, 1H), 7.13-7.09 (m, 3H), 7.05-7.02 (m, 4H), 6.80-6.76 (m, 2H), 6.68 (d, J = 8.0 Hz, 2H), 3.87 (s, 4H), 3.47 (s, 4H).

[0034] 13C NMR (100 MHz, CDCl3) δ 144.6, 139.8, 130.8, 129.1, 129.0, 127.7, 126.6, 125.1, 118.8, 116.0, 38.0.

[0035] Example 2 A method for synthesizing dibenzyl-α,α-diphenylamine compounds, the reaction equation of which is as follows: The specific experimental steps are as follows: (1) Mix terephthalaldehyde (10.0 g, 74.6 mmol), benzylamine (16.3 mL, 149.2 mmol), and toluene (75 mL), and add titanium tetrachloride (8.2 mL, 74.6 mmol). Heat at 110 °C o The reaction mixture was heated at C for 15 min. Then, 14.4 mL of 2-cyclohexenone (149.2 mmol) and 4.1 mL of benzylamine (37.3 mmol) were added to the reaction solution. After reacting for 1 h, 7.2 mL of 2-cyclohexenone (74.6 mmol) was added, and the reaction was continued at 110 °C. o After reacting at C for 2 hours, the reaction was stopped and cooled to room temperature. The mixture was poured into ice water and the organic phase toluene layer was extracted and separated. The organic phase was then washed twice with water, dried with anhydrous Na2SO4, and the solvent was removed by concentration under reduced pressure. The residue was purified by silica gel column chromatography to obtain a yellow solid, which was 26.2 g of intermediate II-2, with a yield of 75%.

[0036] The NMR spectrum data of intermediate II-2 are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.38-7.35 (m, 6H), 7.32-7.28 (m, 2H), 7.26-7.22 (m, 10H), 6.90-6.86 (m, 2H), 6.76 (d, J = 8.0 Hz, 2H), 4.35 (s, 4H), 4.12-4.03 (m, 2H), 4.00 (s, 4H).

[0037] 13 C NMR (100 MHz, CDCl3) δ 145.9, 139.3, 137.6, 130.6, 129.0, 128.6, 127.9, 127.3, 127.1, 124.8, 117.3, 111.0, 48.0, 38.0.

[0038] (2) Intermediate II-2 (26.2 g, 56.0 mmol), acetic acid (0.6 mL, 11.2 mmol) and dichloromethane (112 mL) were mixed, and 10% Pd-C (2.6 g, 10 wt%) was added. H2 was introduced and the reaction was carried out at room temperature and pressure for 6 h. After the reaction was completed, the pH of the reaction solution was adjusted to about 9.5 with a 5 mol / L sodium hydroxide aqueous solution. Pd-C was removed by filtration, the organic phase was separated, the organic phase was dried with anhydrous Na2SO4, the solvent was removed by vacuum concentration, and the residue was recrystallized with petroleum ether and ethyl acetate to obtain 15.5 g of grayish-white solid compound I-2 with a yield of 96%.

[0039] The NMR spectrum data of compound I-2 are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.05-6.94 (m, 8H), 6.70-6.63 (m, 2H), 6.56(d, J = 8.0 Hz, 2H), 3.76 (s, 4H), 3.39 (s, 4H).

[0040] 13 C NMR (100 MHz, CDCl3) δ 144.7, 137.5, 130.9, 128.9, 127.7, 125.2, 118.9, 116.0, 37.7.

[0041] Example 3 A method for synthesizing dibenzyl-α,α-diphenylamine compounds, the reaction equation of which is as follows: The specific experimental steps are as follows: (1) Mix 2,6-naphthalenedicarbaldehyde (10.0 g, 54.3 mmol), benzylamine (11.9 mL, 108.6 mmol), and toluene (54 mL), and add titanium tetrachloride (6.0 mL, 54.3 mmol). Heat at 110 °C o The reaction mixture was heated at C for 15 min. Then, 10.5 mL of 2-cyclohexenone (108.6 mmol) and 3.0 mL of benzylamine (27.2 mmol) were added to the reaction solution. After reacting for 1 h, 5.3 mL of 2-cyclohexenone (54.3 mmol) was added, and the reaction was continued at 110 °C. oAfter reacting for 2 hours, the reaction was stopped and cooled to room temperature. The mixture was poured into ice water and the organic toluene layer was extracted and separated. The organic phase was then washed twice with water, dried with anhydrous Na2SO4, and the solvent was removed by concentration under reduced pressure. The residue was purified by silica gel column chromatography to obtain a yellow solid, which was 20.5 g of intermediate II-3, with a yield of 73%.

[0042] The NMR spectrum data of intermediate II-3 are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.67 (d, J = 8.0 Hz, 2H), 7.60 (s, 2H), 7.34(d, J = 8.0 Hz, 2H), 7.22-7.14 (m, 10H), 7.05 (d, J = 8.0 Hz, 4H), 6.80-6.75(m, 2H), 6.67 (d, J = 8.0 Hz, 2H), 4.24 (s, 4H), 4.09 (s, 4H), 4.08-3.97 (m, 2H).

[0043] 13 C NMR (100 MHz, CDCl3) δ 146.2, 139.3, 136.6, 132.6, 130.8, 128.6,128.2, 128.1, 127.5, 127.3, 127.1, 126.7, 124.6, 117.4, 111.1, 48.1, 38.6.

[0044] (2) Intermediate II-3 (20.5 g, 39.6 mmol), acetic acid (0.5 mL, 7.9 mmol) and dichloromethane (80 mL) were mixed, and 10% Pd-C (2.1 g, 10 wt%) was added. H2 was introduced and the reaction was carried out at room temperature and pressure for 6 h. After the reaction was completed, the pH of the reaction solution was adjusted to about 9.5 with a 5 mol / L sodium hydroxide aqueous solution. Pd-C was removed by filtration, the organic phase was separated, the organic phase was dried with anhydrous Na2SO4, the solvent was removed by vacuum concentration, and the residue was recrystallized with petroleum ether and ethyl acetate to obtain 12.7 g of grayish-white solid compound I-3 with a yield of 95%.

[0045] The NMR spectrum data of compound I-3 are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.70 (d, J= 8.0 Hz, 2H), 7.59 (s, 2H), 7.33(d, J = 8.0 Hz, 2H), 7.16-7.12 (m, 4H), 6.84-6.78 (m, 2H), 6.70 (d, J = 8.0 Hz, 2H), 4.06 (s, 4H), 3.43 (s, 4H).

[0046] 13 C NMR (100 MHz, CDCl3) δ 144.9, 136.7, 132.5, 131.08, 128.1, 127.9, 127.5, 126.5, 125.1, 118.9, 116.1, 38.4.

[0047] Example 4 A method for synthesizing dibenzyl-α,α-diphenylamine compounds, the reaction equation of which is as follows: The specific experimental steps are as follows: (1) Mix 1,1'-biphenyl-4,4'-dicarboxaldehyde (10.0 g, 47.6 mmol), benzylamine (10.4 mL, 95.2 mmol), and toluene (48 mL), and add titanium tetrachloride (5.2 mL, 47.6 mmol). Heat at 110 °C o The reaction mixture was heated at C for 15 min. Then, 2-cyclohexenone (9.2 mL, 95.2 mmol) and benzylamine (2.6 mL, 23.8 mmol) were added to the reaction solution. After reacting for 1 h, 4.6 mL of 2-cyclohexenone (47.6 mmol) was added, and the reaction was continued at 110 °C. o After reacting at C for 2 hours, the reaction was stopped, cooled to room temperature, and the mixture was poured into ice water. The organic phase toluene layer was extracted and separated. The organic phase was then washed twice with water, dried with anhydrous Na2SO4, concentrated under reduced pressure to remove the solvent, and the residue was purified by silica gel column chromatography to obtain a yellow solid, which was 20.2 g of intermediate II-4, with a yield of 78%.

[0048] The NMR spectrum data of intermediate II-4 are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.40 (d, J = 8.0 Hz, 4H), 7.17-7.10 (m, 10H), 7.09-7.04 (m, 4H), 7.03-6.90 (m, 6H), 6.67-6.63 (m, 2H), 6.54 (d,J = 8.0 Hz, 2H), 4.16 (s, 4H), 3.84 (s, 4H).

[0049] 13 C NMR (100 MHz, CDCl3) δ 146.1, 139.4, 139.2, 138.5, 130.8, 129.1,128.6, 128.1, 127.3, 127.2, 124.6, 117.4, 111.1, 48.2, 38.0.

[0050] (2) Intermediate II-4 (20.2 g, 37.1 mmol), acetic acid (0.4 mL, 7.4 mmol) and dichloromethane (74 mL) were mixed, and 10% Pd-C (2.0 g, 10 wt%) was added. H2 was introduced and the reaction was carried out at room temperature and pressure for 6 h. After the reaction was completed, the pH of the reaction solution was adjusted to about 9.5 with a 5 mol / L sodium hydroxide aqueous solution. Pd-C was removed by filtration, the organic phase was separated, the organic phase was dried with anhydrous Na2SO4, the solvent was removed by vacuum concentration, and the residue was recrystallized with petroleum ether and ethyl acetate to obtain 12.8 g of grayish-white solid compound I-4 with a yield of 95%.

[0051] The NMR spectrum data of compound I-4 are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.39 (d, J = 8.0 Hz, 4H), 7.18-7.12 (m, 4H), 7.05-6.96 (m, 4H), 6.72-6.67 (m, 2H), 6.58 (d, J = 8.0 Hz, 2H), 3.83 (s, 4H), 3.42 (s, 4H).

[0052] 13 C NMR (100 MHz, CDCl3) δ 144.8, 139.1, 138.5, 131.1, 129.0, 127.9,127.3, 125.1, 118.9, 116.1, 37.8.

[0053] Example 5 A method for synthesizing dibenzyl-α,α-diphenylamine compounds, the reaction equation of which is as follows: The specific experimental steps are as follows: (1) Mix 4,4'-oxydibenzaldehyde (10.0 g, 44.2 mmol), benzylamine (9.7 mL, 88.4 mmol), and toluene (44 mL), and add titanium tetrachloride (4.9 mL, 44.2 mmol). Heat at 110 °C o The reaction mixture was heated at C for 15 min. Then, 2-cyclohexenone (8.6 mL, 88.4 mmol) and benzylamine (2.4 mL, 22.1 mmol) were added to the reaction solution. After reacting for 1 h, 4.3 mL of 2-cyclohexenone (44.2 mmol) was added, and the reaction was continued at 110 °C. o After reacting at C for 2 hours, the reaction was stopped and cooled to room temperature. The mixture was poured into ice water and the organic phase toluene layer was extracted and separated. The organic phase was then washed twice with water, dried with anhydrous Na2SO4, and the solvent was removed by concentration under reduced pressure. The residue was purified by silica gel column chromatography to obtain a yellow solid, which was 12.9 g of intermediate II-5, with a yield of 52%.

[0054] The NMR spectrum data of intermediate II-5 are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.04 (t, J = 6.0 Hz, 4H), 6.98 (t, J = 6.0 Hz,2H), 6.96-6.86 (m, 12H), 6.72 (d, J = 12.0 Hz, 4H), 6.54 (t, J = 12.0 Hz, 2H), 6.43 (d, J = 6.0 Hz, 2H), 4.02 (s, 4H), 3.70 (s, 2H), 3.64 (s, 4H).

[0055] 13 C NMR (100 MHz, CDCl3) δ 155.9, 145.8, 139.3, 134.1, 130.5, 129.8,128.5, 127.9, 127.2, 127.1, 124.6, 119.0, 117.3, 110.9, 47.9, 37.5.

[0056] (2) Intermediate II-5 (12.9 g, 23.0 mmol), acetic acid (0.3 mL, 4.6 mmol) and dichloromethane (46 mL) were mixed, and 10% Pd-C (1.3 g, 10 wt%) was added. H2 was introduced and the reaction was carried out at room temperature and pressure for 6 h. After the reaction was completed, the pH of the reaction solution was adjusted to about 9.5 with a 5 mol / L sodium hydroxide aqueous solution. Pd-C was removed by filtration, the organic phase was separated, the organic phase was dried with anhydrous Na2SO4, the solvent was removed by vacuum concentration, and the residue was recrystallized with petroleum ether and ethyl acetate to obtain 8.3 g of grayish-white solid compound I-5 with a yield of 95%.

[0057] The NMR spectrum data of compound I-5 are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.02-6.95 (m, 6H), 6.92 (d, J = 6.0 Hz, 2H), 6.79 (d, J = 12.0 Hz, 4H), 6.63 (t, J = 12.0 Hz, 2H), 6.52 (d, J = 6.0 Hz, 2H), 3.72 (s, 4H), 3.36 (s, 4H).

[0058] 13 C NMR (100 MHz, CDCl3) δ 155.8, 144.7, 134.1, 130.8, 129.8, 127.7,125.1, 119.0, 118.8, 116.0, 37.3.

[0059] Example 6 A method for synthesizing dibenzyl-α,α-diphenylamine compounds, the reaction equation of which is as follows: The specific experimental steps are as follows: (1) Mix 2,5-furandicarboxaldehyde (6.3 g, 50.8 mmol), benzylamine (11.1 mL, 101.6 mmol), and toluene (51 mL), and add titanium tetrachloride (5.6 mL, 50.8 mmol). Heat at 110 °C o The reaction mixture was heated at C for 15 min. Then, 2-cyclohexenone (9.8 mL, 101.6 mmol) and benzylamine (2.8 mL, 25.4 mmol) were added to the reaction solution. After reacting for 1 h, 4.9 mL of 2-cyclohexenone (50.8 mmol) was added, and the reaction was continued at 110 °C. oAfter reacting for 2 hours, the reaction was stopped and cooled to room temperature. The mixture was poured into ice water and the organic toluene layer was extracted and separated. The organic phase was then washed twice with water, dried with anhydrous Na2SO4, and the solvent was removed by concentration under reduced pressure. The residue was purified by silica gel column chromatography to give a pale yellow solid, which was 17.4 g of intermediate II-6, with a yield of 75%.

[0060] The NMR spectrum data of intermediate II-6 are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.34-7.21 (m, 10H), 7.13-7.09 (m, 2H), 7.04(d, J = 4.0 Hz, 2H), 6.70-6.66 (m, 2H), 6.60 (d, J = 8.0 Hz, 2H), 5.89 (s, 2H), 4.26 (s, 6H), 3.80 (s, 4H).

[0061] 13 C NMR (100 MHz, CDCl3) δ 152.4, 146.1, 139.5, 130.4, 128.7, 128.2, 127.4, 127.2, 122.5, 117.5, 111.2, 48.1, 31.3.

[0062] (2) Intermediate II-6 (17.4 g, 37.9 mmol), acetic acid (0.4 mL, 7.6 mmol) and dichloromethane (76 mL) were mixed, and 10% Pd-C (1.7 g, 10 wt%) was added. H2 was introduced and the reaction was carried out at room temperature and pressure for 6 h. After the reaction was completed, the pH of the reaction solution was adjusted to about 9.5 with a 5 mol / L sodium hydroxide aqueous solution. Pd-C was removed by filtration, the organic phase was separated, the organic phase was dried with anhydrous Na2SO4, the solvent was removed by vacuum concentration, and the residue was recrystallized with petroleum ether and ethyl acetate to give 9.7 g of pale yellow solid compound I-6 with a yield of 92%.

[0063] The NMR spectrum data of compound I-6 are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.07-7.02 (m, 4H), 6.74-6.70 (m, 2H), 6.62(d, J = 8.0 Hz, 2H), 5.83 (s, 2H), 3.78 (s, 4H), 3.56 (s, 4H).

[0064] 13 C NMR (100 MHz, CDCl3) δ 152.5, 144.9, 130.7, 128.0, 122.6, 119.0, 116.2, 107.0, 31.1.

[0065] Example 7 The difference between this embodiment and Example 1 is that in step (1), the reaction solvent is replaced with 1,4-dioxane, and the heating reaction temperature is 100°C. o C. Under the same conditions as in Example 1, 12.5 g of intermediate II-1 was obtained with a yield of 53%. The 12.5 g intermediate II-1 was processed according to the hydrogenation debenzylation method described in step (2) to obtain 7.1 g of target product I-1 with a yield of 92%.

[0066] Example 8 The difference between this embodiment and Example 1 is that in step (1), the reaction solvent is replaced with acetonitrile, and the heating temperature is 80°C. o C, with the other conditions the same as in Example 1, 12.1 g of intermediate II-2 was obtained, with a yield of 51%; the 12.1 g intermediate II-2 was operated on according to the hydrogenation debenzylation method described in step (2) to obtain 7.2 g of target product I-2, with a yield of 97%.

[0067] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A method for synthesizing dibenzyl-α,α-diphenylamine compounds, characterized in that, Specifically, the following steps are included: (1) Using aromatic dialdehyde, 2-cyclohexenone, and benzylamine as raw materials, the reaction was carried out in an organic solvent under the catalysis of titanium tetrachloride; after the reaction was completed, the intermediate shown in Formula II was obtained by separation and purification. (2) The intermediate shown in Formula II is debenzylated to obtain dibenzyl-α,α-diphenylamine compounds as shown in Formula I; The aromatic dialdehyde has any one of the following structural formulas: 、 、 、 、 、 ； The structural formula of the 2-cyclohexenone is: ; The structural formula of the benzylamine is: ; The structural formula of formula II is: ; The structural formula of Formula I is: ; In the structures of Formula II and Formula I, the Ar group is one of the following structures: , , , , and .

2. The method for synthesizing dibenzyl-α,α-diphenylamine compounds according to claim 1, characterized in that, The molar ratio of aromatic dialdehyde, 2-cyclohexenone, and benzylamine in step (1) is 1:3:2.

5.

3. The method for synthesizing dibenzyl-α,α-diphenylamine compounds according to claim 1, characterized in that, The molar ratio of aromatic dialdehyde and titanium tetrachloride in step (1) is 1:

1.

4. The method for synthesizing dibenzyl-α,α-diphenylamine compounds according to claim 1, characterized in that, The organic solvent mentioned in step (1) is one of toluene, 1,1,2,2-tetrachloroethane, 1,4-dioxane, and acetonitrile.

5. The method for synthesizing dibenzyl-α,α-diphenylamine compounds according to claim 1, characterized in that, The concentration of the aromatic dialdehyde in the organic solvent in step (1) is 1 mol / L.

6. The method for synthesizing dibenzyl-α,α-diphenylamine compounds according to claim 1, characterized in that, The heating reaction conditions described in step (1) are: 80~110°C. o C reaction for 3 hours.

7. The method for synthesizing dibenzyl-α,α-diphenylamine compounds according to claim 1, characterized in that, The debenzylation in step (2) specifically involves: mixing the intermediate, acetic acid and organic solvent, adding Pd-C, bubbling H2, and reacting at room temperature for 6 hours; after the reaction is completed, adjusting the pH of the reaction solution to 9-10, filtering to remove Pd-C, and separating and purifying.

8. The method for synthesizing dibenzyl-α,α-diphenylamine compounds according to claim 7, characterized in that, The Pd-C is a Pd-C catalyst with a Pd metal loading of 10% by mass, wherein palladium accounts for 10% of the total mass of the Pd-C catalyst.

9. The method for synthesizing dibenzyl-α,α-diphenylamine compounds according to claim 7, characterized in that, The molar ratio of the intermediate to acetic acid is 1:0.2; the amount of Pd-C used is 10% of the mass of the intermediate; the concentration of the intermediate in the organic solvent is 0.5 mol / L.

10. The method for synthesizing dibenzyl-α,α-diphenylamine compounds according to claim 7, characterized in that, The organic solvent is one of dichloromethane, tetrahydrofuran, methanol, ethanol, and toluene.

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