Tetrahydropyrrole derivative and synthesis method thereof

Abstract

The invention discloses a tetrahydropyrrole derivative and a synthesis method thereof. The synthetic method comprises the following steps: in the presence of a heterogeneous supported bimetallic catalyst and an organic solvent, mixing and reacting amines and dihydric alcohols to prepare the tetrahydropyrrole derivative. According to the method disclosed by the invention, not only is the use of an alkaline additive avoided and the use requirement of equipment reduced, but also the high yield and high purity of the finally prepared tetrahydropyrrole derivative are ensured.

Description

Technical Field

[0001] The present invention relates to a tetrahydropyrrole derivative and a synthesis method thereof, in particular to a novel method for preparing a tetrahydropyrrole compound by dehydrogenation-coupling of an organic amine and a diol catalyzed by a heterogeneous supported bimetallic catalyst. Background Art

[0002] Tetrahydropyrrole derivatives (N-substituted tetrahydropyrrole compounds) are important components of heterocyclic compounds and are key building blocks of many natural products, pharmaceuticals, and agricultural chemicals. They possess excellent biological activities, such as antibacterial, antitumor, and antifungal properties. Numerous methods for synthesizing tetrahydropyrrole derivatives have been reported in the literature and patents, including nucleophilic reactions of halogenated compounds with primary aromatic amines, cross-coupling reactions of aryl halides with N-unsubstituted heterocyclic compounds, coupling reactions of cyclic ethers with primary aromatic amines, and reductive amination of dicarbonyl compounds. However, some of these methods require the use of halogenating agents and strong base additives, generating significant amounts of waste. Some reaction systems utilize raw materials with specialized structures that are difficult to obtain and expensive. Some reactions have harsh conditions and are incompatible with heat-sensitive groups, hindering their industrial application. Therefore, developing a method for synthesizing tetrahydropyrrole derivatives that utilizes mild conditions, broad raw material resources, and eliminates the generation of chemical waste is of great significance to the chemical industry.

[0003] Diols are readily available industrial raw materials, and some can be obtained from renewable biomass resources, making them a good class of organic synthesis intermediates. Tetrahydropyrrole derivatives can be prepared using diols and organic amines as raw materials through a catalytic dehydrogenation-coupling reaction. In 1987, Waranabe et al. used RuCl3(PPh3)3 as a catalyst and aromatic amines and 1,4-butenediol as raw materials to synthesize a series of N-aryl-tetrahydropyrrole compounds (140-180°C, 5-24h) with yields of 45-91% (Bull. Chem. Soc. Jpn., 1987, 60, 3456-3458). Barta et al. used 1,4-butanediol and benzylamine as raw materials (Nat. Commun. 2θ14, 5, 5602) to synthesize a series of tetrahydropyrrole compounds with different structures under the co-catalysis of an iron-based complex and Me3NO. It's not difficult to see that all of the aforementioned reaction systems are homogeneous metal-catalyzed systems, requiring a strong base as an additive for activation. Some of these reaction systems also have specific requirements for raw materials and are incompatible with common diols. These limitations restrict the use of diols as synthons, necessitating the development of efficient tetrahydropyrrole synthesis methods suitable for common diols.

[0004] In view of this, the present invention is proposed. Summary of the Invention

[0005] This invention designs and provides a novel method for synthesizing tetrahydropyrrole derivatives. Using biomass-based diols and organic amines as raw materials, this method employs a heterogeneous supported bimetallic catalytic system to synthesize tetrahydropyrrole derivatives through a receptor-free dehydrogenation-coupling reaction of the biomass-based diols and organic amines, achieving high reaction efficiency and yield. The bimetallic catalyst in this reaction system features simple synthesis steps, excellent stability, and high substrate compatibility, while still exhibiting a good catalytic effect without the addition of a strong base. The development of this method will provide a new approach for the green and sustainable synthesis of tetrahydropyrrole derivatives.

[0006] To achieve the above-mentioned object of the present invention, the first aspect of the present invention provides a method for synthesizing a tetrahydropyrrole derivative, comprising mixing and reacting an amine represented by Formula 1a with a diol represented by Formula 2a in the presence of a heterogeneous supported bimetallic catalyst and an organic solvent to obtain a tetrahydropyrrole derivative represented by Formula 3a, wherein the reaction formula is as follows:

[0007]

[0008] wherein R is selected from one of the following groups: aryl, substituted aryl, alkyl and substituted alkyl;

[0009] Wherein, R1 and R2 are each independently selected from one of the following groups: hydrogen, alkyl.

[0010] According to some embodiments of the present invention, the heterogeneous supported bimetallic catalyst is supported by α-Al2O3 and loaded with metal Cu and Co; preferably, the heterogeneous supported bimetallic catalyst is x wt% Cu-ywt% Co / α-Al2O3, wherein wt% refers to weight percentage; x wt% Cu means that the weight proportion of Cu in the total catalyst is x wt%; y wt% Co means that the weight proportion of Co in the total catalyst is y wt%.

[0011] According to some embodiments of the present invention, based on the total weight of the catalyst, x+y=15-20, which means that the total loading of Cu and Co is 15 wt% to 20 wt%.

[0012] According to some embodiments of the present invention, x and y are each independently 3 to 12, which means that the loading of Cu and Co single metals is each independently 3 to 12 wt%. That is, the loading of Cu can be 3 to 12 wt%, the loading of Co can also be 3 to 12 wt%, and the total loading of Cu and Co is 15 wt%. The catalyst is, for example, but not limited to: 5 wt% Cu-10 wt% Co / α-Al2O3, 10 wt% Cu-5 wt% Co / α-Al2O3, 12 wt% Cu-5 wt% Co / α-Al2O3. Preferably, the heterogeneous supported bimetallic catalyst is 10 wt% Cu-5 wt% Co / α-Al2O3.

[0013] In the present invention, the heterogeneous supported bimetallic catalyst used can be prepared by an impregnation method, and its preparation method is, for example, but not limited to:

[0014] A certain amount of commercially available oxide support and metal salt precursor were weighed and mixed, water was added and stirred, and then the moisture was removed at 40°C using a rotary evaporator. The obtained solid was dried in an oven at 110°C for 12 hours, ground into powder, calcined at a specific temperature in a muffle furnace for a period of time, taken out after cooling to room temperature, and finally reduced under specific atmosphere conditions in a tubular furnace for a period of time, naturally cooled to room temperature and taken out to obtain a supported heterogeneous metal catalyst.

[0015] According to some embodiments of the present invention, the reaction conditions include: a reaction temperature of 130-170°C, and a reaction time of 4-24 hours. For example, but not limited to, a reaction temperature of 130°C, 140°C, 150°C, 160°C, or 170°C, and a reaction time of 4 hours, 8 hours, 12 hours, 16 hours, 20 hours, or 24 hours.

[0016] According to some embodiments of the present invention, the organic solvent is selected from one or more of p-xylene, o-xylene, and m-xylene.

[0017] According to some embodiments of the present invention, the amount of the organic solvent used is 2-4 mL per 0.5 mmol of amine, for example but not limited to: the amount of the organic solvent used is 2 mL, 2.5 mL, 3 mL, 3.5 mL, or 4 mL per 0.5 mmol of amine.

[0018] According to some embodiments of the present invention, the dosage of the heterogeneously supported bimetallic catalyst is 50 to 200 mg per 0.5 mmol of amine. For example, but not limited to, the dosage of the heterogeneously supported bimetallic catalyst is 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 110 mg, 120 mg, 130 mg, 140 mg, 150 mg, 160 mg, 170 mg, 180 mg, 190 mg, or 200 mg per 0.5 mmol of amine.

[0019] According to some embodiments of the present invention, the molar ratio of the diol to the amine is 1-6:1, for example but not limited to 1:1, 1.5:1, 2:1, 2.5:1, 3:1, 3.5:1, 4:1, 4.5:1, 5:1, 5.5:1, and 6:1.

[0020] According to some embodiments of the invention, R is independently selected from one of the following groups: phenyl, 4-methylphenyl, 2-methylphenyl, 4-methoxyphenyl, 4-esterphenyl, 4-acetophenone, 4-fluorophenyl, 2-isopropylphenyl, naphthyl, phenethyl, isooctyl, hexyl, octyl.

[0021] According to some embodiments of the present invention, R1 is selected from one of the following groups: hydrogen, methyl.

[0022] According to some embodiments of the present invention, R2 is selected from one of the following groups: hydrogen, methyl.

[0023] According to some embodiments of the present invention, the amine is selected from one or more of aniline, 4-methylaniline, 2-methylaniline, 4-methoxyaniline, 4-aminobenzoic acid methyl ester, 4-aminoacetophenone, 4-fluoroaniline, 2-isopropylaniline, naphthylamine, phenethylamine, isooctylamine, hexylamine, and octylamine.

[0024] According to some embodiments of the present invention, the diols are selected from one or more of 1,4-butanediol, 1,5-pentanediol, and 2,5-hexanediol.

[0025] The second aspect of the present invention provides a tetrahydropyrrole derivative synthesized according to the above method.

[0026] Beneficial effects of the present invention:

[0027] (1) The synthesis method of the present invention uses a heterogeneous catalyst to catalyze the dehydrogenation-coupling reaction of biomass-based diols and organic amines under mild conditions without receptors, thereby obtaining tetrahydropyrrole derivatives in high yields, with water as the only by-product.

[0028] (2) In the present invention, the synthesis of tetrahydropyrrole derivatives does not require any additional base additives, the synthesis method does not require the addition of strong bases, and the reaction conditions are mild.

[0029] (3) Compared to previous studies, the heterogeneously supported bimetallic catalytic system described in this invention achieves a significant breakthrough in catalyst separation and recovery, and is widely applicable to a variety of functionalized organic amine raw materials. This invention is a valuable supplement and beneficial improvement to existing tetrahydropyrrole derivative synthesis systems. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] In order to more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the specific embodiments or the description of the prior art. Obviously, the drawings described below are some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0031] Figure 1 This is the H NMR spectrum of the product obtained in Example 2 of the present invention.

[0032] Figure 2 The C NMR spectrum of the product obtained in Example 2 of the present invention is shown in FIG.

[0033] Figure 3 This is a scanning electron microscope (SEM) image of the 10wt% Cu-5wt% Co / α-Al2O3 support used in Example 1 of the present invention.

[0034] Figure 4 This is a transmission electron microscope (TEM) image of the 10wt% Cu-5wt% Co / α-Al2O3 catalyst synthesized in Example 1 of the present invention. DETAILED DESCRIPTION

[0035] The following will clearly and completely describe the technical solutions of the present invention in conjunction with the embodiments. Obviously, the embodiments described are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0036] The present invention is further described below by way of examples. Unless otherwise specified, the materials in the examples were prepared according to existing methods or directly purchased from the market.

[0037] Example 1

[0038] The 10wt% Cu-5wt% Co / α-Al2O3 bimetallic catalyst was prepared by an impregnation method, comprising the following steps:

[0039] First, α-Al2O3 was prepared. Pseudo-thin aluminum oxide was placed in a muffle furnace and calcined at 1100°C for 4 hours. After cooling to room temperature, α-Al2O3 was obtained. Next, 1.7g of α-Al2O3, 0.755g of Cu(NO3)2·3H2O, and 0.494g of Co(NO3)2·6H2O were weighed and mixed in a 50mL round-bottom flask. 15mL of deionized water was added and stirred at 750 rpm for 12 hours at room temperature. The water was then removed using a rotary evaporator at 40°C. The resulting solid was dried in a 110°C oven for 12 hours and then ground in a mortar while hot. The resulting powder was calcined in a muffle furnace at 400°C for 4 hours, cooled to room temperature, and then removed. Finally, the powder was reduced in a tube furnace at 500°C under 20% H2 / N2 for 3 hours. The mixture was naturally cooled to room temperature and removed to obtain a 10wt% Cu-5wt% Co / α-Al2O3 catalyst. The structural characterization of the obtained catalyst is as follows Figure 3 and 4 As shown. Figure 3 It was found that the catalyst surface showed a worm-like structure and was distributed in an orderly manner; Figure 4 It was found that the metal nanoparticles were uniformly dispersed with an average particle size of 4.35 nm, proving that the metal Cu and Co were successfully loaded and evenly distributed on the support surface.

[0040] Example 2

[0041] 100 mg of 10 wt% Cu-5 wt% Co / α-Al2O3 (Example 1), 0.5 mmol aniline, 0.6 mmol 2,5-hexanediol and 3 mL p-xylene were added to a 35 mL pressure tube, purged with N2 three times, and reacted at 160°C with a stirring speed of 800 rpm for 24 h. The reaction product was analyzed by nuclear magnetic resonance (eg Figure 1 、 Figure 2 ) confirmed that the main product was indeed N-phenyl-2,5-dimethyltetrahydropyrrole. Using naphthalene as the internal standard, quantitative analysis by gas chromatography revealed a yield of 93% for N-phenyl-2,5-dimethyltetrahydropyrrole. The yield was calculated as follows: Target product yield (%) = actual amount of target product obtained / theoretical amount of target product.

[0042] Comparative Example 1

[0043] It is basically the same as Example 2, except that 10wt% Cu-5wt% Co / TiO2 with TiO2 as the carrier is used instead of 10wt% Cu-5wt% Co / α-Al2O3 in Example 2. The test results show that the yield of N-phenyl-2,5-dimethyltetrahydropyrrole obtained in this example is 38%.

[0044] The preparation method of the 10 wt % Cu-5 wt % Co / TiO 2 is consistent with the steps of Example 1, except that commercially available TiO 2 is used instead of α-Al 2 O 3 .

[0045] Comparative Example 2

[0046] It is basically the same as Example 2, except that 10wt% Cu-5wt% Co / ZrO2 with ZrO2 as the carrier is used instead of 10wt% Cu-5wt% Co / α-Al2O3 in Example 2. The test results show that the yield of N-phenyl-2,5-dimethyltetrahydropyrrole obtained in this example is 12%.

[0047] The preparation method of the 10 wt % Cu-5 wt % Co / ZrO 2 is consistent with the steps of Example 1, except that commercially available ZrO 2 is used instead of α-Al 2 O 3 .

[0048] Comparative Example 3

[0049] It is basically the same as Example 2, except that 10wt% Cu-5wt% Co / MgO with MgO as the carrier is used instead of 10wt% Cu-5wt% Co / α-Al2O3 in Example 2. The test results show that the yield of N-phenyl-2,5-dimethyltetrahydropyrrole obtained in this embodiment of the present invention is 9%.

[0050] The preparation method of the 10 wt % Cu-5 wt % Co / MgO is consistent with the steps of Example 1, except that commercially available MgO is used instead of α-Al 2 O 3 .

[0051] Comparative Example 4

[0052] The reaction mixture was basically the same as Example 2, except that 10 wt% Cu-5 wt% Co / MgAl-LDO with MgAl-LDO as the carrier was used instead of 10 wt% Cu-5 wt% Co / α-Al2O3 in Example 2. The test results showed that the yield of N-phenyl-2,5-dimethyltetrahydropyrrole obtained in this example was 20%.

[0053] The preparation method of the 10 wt % Cu-5 wt % Co / MgAl-LDO is the same as that of Example 1, except that commercially available MgAl-LDO is used instead of α-Al 2 O 3 .

[0054] Comparative Example 5

[0055] It is basically the same as Example 2, except that 15wt% Cu / α-Al2O3 is used instead of 10wt% Cu-5wt% Co / α-Al2O3 in Example 2. The test results show that the yield of N-phenyl-2,5-dimethyltetrahydropyrrole obtained in this example is 24%.

[0056] Comparative Example 6

[0057] It is basically the same as Example 2, except that 15wt% Co / α-Al2O3 is used instead of 10wt% Cu-5wt% Co / α-Al2O3 in Example 2. The test results show that the yield of N-phenyl-2,5-dimethyltetrahydropyrrole obtained in this example is 0.

[0058] Comparative Example 7

[0059] It is basically the same as Example 2, except that 10wt% Cu-5wt% Ni / α-Al2O3 is used instead of 10wt% Cu-5wt% Co / α-Al2O3 in Example 2. The test results show that the yield of N-phenyl-2,5-dimethyltetrahydropyrrole obtained in this example is 7%.

[0060] Comparative Example 8

[0061] It is basically the same as Example 2, except that 10wt% Cu-5wt% Fe / α-Al2O3 is used instead of 10wt% Cu-5wt% Co / α-Al2O3 in Example 2. The test results show that the yield of N-phenyl-2,5-dimethyltetrahydropyrrole obtained in this example is 41%.

[0062] Comparative Example 9

[0063] It is basically the same as Example 2, except that 10wt% Cu-5wt% Cr / α-Al2O3 is used instead of 10wt% Cu-5wt% Co / α-Al2O3 in Example 2. The test results show that the yield of N-phenyl-2,5-dimethyltetrahydropyrrole obtained in this example is 27%.

[0064] Comparative Example 10

[0065] It is basically the same as Example 2, except that 10wt% Cu-5wt% Pd / α-Al2O3 is used instead of 10wt% Cu-5wt% Co / α-Al2O3 in Example 2. The test results show that the yield of N-phenyl-2,5-dimethyltetrahydropyrrole obtained in this example is 47%.

[0066] The above comparison shows that the catalyst with the best catalytic effect is the Cu-Co / α-Al2O3 catalyst.

[0067] Proportions of different metals:

[0068] Example 3

[0069] It is basically the same as Example 2, except that 12wt% Cu-3wt% Co / α-Al2O3 is used instead of 10wt% Cu-5wt% Co / α-Al2O3 in Example 2. The test results show that the yield of N-phenyl-2,5-dimethyltetrahydropyrrole obtained in this example is 65%.

[0070] Example 4

[0071] It is basically the same as Example 2, except that 5wt% Cu-10wt% Co / α-Al2O3 is used instead of 10wt% Cu-5wt% Co / α-Al2O3 in Example 2. The test results show that the yield of N-phenyl-2,5-dimethyltetrahydropyrrole obtained in this example is 74%.

[0072] Example 5

[0073] It is basically the same as Example 2, except that 3wt% Cu-12wt% Co / α-Al2O3 is used instead of 10wt% Cu-5wt% Co / α-Al2O3 in Example 2. The test results show that the yield of N-phenyl-2,5-dimethyltetrahydropyrrole obtained in this example is 62%.

[0074] Example 6

[0075] It is basically the same as Example 2, except that 8wt% Cu-12wt% Co / α-Al2O3 is used instead of 10wt% Cu-5wt% Co / α-Al2O3 in Example 2. The test results show that the yield of N-phenyl-2,5-dimethyltetrahydropyrrole obtained in this example is 89%.

[0076] Example 7

[0077] It is basically the same as Example 2, except that 10t% Cu-10wt% Co / α-Al2O3 is used instead of 10wt% Cu-5wt% Co / α-Al2O3 in Example 2. The test results show that the yield of N-phenyl-2,5-dimethyltetrahydropyrrole obtained in this example is 92%.

[0078] The above examples show that the present invention can achieve excellent catalytic effects when the total catalyst loading is 15-20 wt% and the two metals are independently loaded at 3 wt%-12 wt%.

[0079] Different catalyst dosage:

[0080] Example 8

[0081] The reaction mixture was basically the same as Example 2, except that 200 mg of 10 wt% Cu-5 wt% Co / α-Al2O3 catalyst was used instead of 100 mg of 10 wt% Cu-5 wt% Co / α-Al2O3 in Example 2. The test results showed that the yield of N-phenyl-2,5-dimethyltetrahydropyrrole obtained in this example was 99%.

[0082] Example 9

[0083] The method is basically the same as Example 2, except that 150 mg of 10 wt% Cu-5 wt% Co / α-Al2O3 catalyst is used instead of 100 mg of 10 wt% Cu-5 wt% Co / α-Al2O3 in Example 2. The test results show that the yield of N-phenyl-2,5-dimethyltetrahydropyrrole obtained in this example is 95%.

[0084] Example 10

[0085] The method is basically the same as Example 2, except that 50 mg of 10 wt% Cu-5 wt% Co / α-Al2O3 catalyst is used instead of 100 mg of 10 wt% Cu-5 wt% Co / α-Al2O3 in Example 2. The test results show that the yield of N-phenyl-2,5-dimethyltetrahydropyrrole obtained in this example is 79%.

[0086] The above examples show that the present catalytic system can achieve excellent catalytic effects when the catalyst dosage is 50-200 mg.

[0087] Different reaction temperatures:

[0088] Example 11

[0089] The method is basically the same as Example 2, except that the temperature is 130° C. instead of 160° C. in Example 2. The test results show that the yield of N-phenyl-2,5-dimethyltetrahydropyrrole obtained in this example is 71%.

[0090] Example 12

[0091] The method is basically the same as Example 2, except that 140° C. is used instead of 160° C. in Example 2. The test results show that the yield of N-phenyl-2,5-dimethyltetrahydropyrrole obtained in this example is 80%.

[0092] Example 13

[0093] The method is basically the same as Example 2, except that the temperature is 150° C. instead of 160° C. in Example 2. The test results show that the yield of N-phenyl-2,5-dimethyltetrahydropyrrole obtained in this example is 91%.

[0094] Example 14

[0095] The method is basically the same as Example 2, except that the temperature is 170° C. instead of 160° C. in Example 2. The test results show that the yield of N-phenyl-2,5-dimethyltetrahydropyrrole obtained in this example is 89%.

[0096] The above examples show that the catalytic system can achieve excellent catalytic effects when the reaction temperature is 130-170°C.

[0097] Different reaction times:

[0098] Example 15

[0099] The method is basically the same as Example 2, except that 12 hours is used instead of 24 hours in Example 2. The test results show that the yield of N-phenyl-2,5-dimethyltetrahydropyrrole obtained in the embodiment of the present invention is 85%.

[0100] Example 16

[0101] The method is basically the same as Example 2, except that 16 hours is used instead of 24 hours in Example 2. The test results show that the yield of N-phenyl-2,5-dimethyltetrahydropyrrole obtained in the embodiment of the present invention is 90%.

[0102] Example 17

[0103] The method is basically the same as Example 2, except that 20 hours are used instead of 24 hours in Example 2. The test results show that the yield of N-phenyl-2,5-dimethyltetrahydropyrrole obtained in the embodiment of the present invention is 95%.

[0104] Example 18

[0105] The method is basically the same as Example 2, except that 28 hours is used instead of 24 hours in Example 2. The test results show that the yield of N-phenyl-2,5-dimethyltetrahydropyrrole obtained in the embodiment of the present invention is 99%.

[0106] The above examples show that the catalytic system can achieve excellent catalytic effects when the reaction time is 12-28 hours.

[0107] Different solvents and dosage:

[0108] Example 19

[0109] The method is basically the same as Example 2, except that 3 mL of o-xylene is used instead of 3 mL of p-xylene in Example 2. The test results show that the yield of N-phenyl-2,5-dimethyltetrahydropyrrole obtained in this example is 92%.

[0110] Example 20

[0111] The method is basically the same as Example 2, except that 3 mL of m-xylene is used instead of 3 mL of p-xylene in Example 2. The test results show that the yield of N-phenyl-2,5-dimethyltetrahydropyrrole obtained in this example is 95%.

[0112] Example 21

[0113] The method is basically the same as Example 2, except that 3 mL of n-dodecane is used instead of 3 mL of p-xylene in Example 2. The test results show that the yield of N-phenyl-2,5-dimethyltetrahydropyrrole obtained in this example is 75%.

[0114] Example 22

[0115] The method is basically the same as Example 2, except that 2 mL of p-xylene is used instead of 3 mL of p-xylene in Example 2. The test results show that the yield of N-phenyl-2,5-dimethyltetrahydropyrrole obtained in this example is 95%.

[0116] Example 23

[0117] The method is basically the same as Example 2, except that 4 mL of p-xylene is used instead of 3 mL of p-xylene in Example 2. The test results show that the yield of N-phenyl-2,5-dimethyltetrahydropyrrole obtained in this example is 90%.

[0118] The above examples show that the catalytic system can achieve excellent catalytic effects in 2 to 4 mL of organic solvents such as p-xylene (o-xylene, m-xylene).

[0119] Amine and diol substrate expansion:

[0120] Structure table of different tetrahydropyrrole derivatives

[0121]

[0122] Example 24

[0123] The same as Example 2, except that 4-methylaniline, 3mmol 2,5-hexanediol, 150mg

[0124] 10wt% Cu-5wt% Co / α-Al2O3 instead of aniline in Example 2, 0.6mmol 2,5-hexanediol, 100mg

[0125] 10wt% Cu-5wt% Co / α-Al2O3, the test results show that the yield of N-(4-methylphenyl)-2,5-dimethyltetrahydropyrrole (3b) obtained in the embodiment of the present invention is 99%.

[0126] Example 25

[0127] The reaction mixture was basically the same as Example 2, except that 2-methylaniline and 200 mg of 10 wt% Cu-5 wt% Co / α-Al2O3 were used instead of aniline and 10 mg of 10 wt% Cu-5 wt% Co / α-Al2O3 in Example 2. The test results showed that the yield of N-(2-methylphenyl)-2,5-dimethyltetrahydropyrrole (3c) obtained in the present invention was 91%.

[0128] Example 26

[0129] The method is basically the same as Example 2, except that 4-methoxyaniline is used instead of aniline in Example 2. The test results show that the yield of N-(4-methoxyphenyl)-2,5-dimethyltetrahydropyrrole (3d) obtained in the embodiment of the present invention is 94%.

[0130] Example 27

[0131] The reaction was basically the same as Example 2, except that 4-aminobenzoic acid methyl ester, 3 mmol 2,5-hexanediol, and 150 mg 10 wt% Cu-5 wt% Co / α-Al2O3 were used instead of aniline, 0.6 mmol 2,5-hexanediol, and 100 mg 10 wt% Cu-5 wt% Co / α-Al2O3 in Example 2. The test results showed that the yield of N-(4-benzoic acid methyl ester)-2,5-dimethyltetrahydropyrrole (3e) obtained in this embodiment of the present invention was 87%.

[0132] Example 28

[0133] The method is basically the same as Example 2, except that 4-aminoacetophenone, 4 mmol 2,5-hexanediol, 150 mg 10 wt% Cu-5 wt% Co / α-Al2O3, and 48 h are used instead of aniline, 0.6 mmol 2,5-hexanediol, 100 mg 10 wt% Cu-5 wt% Co / α-Al2O3, and 24 h in Example 2. The test results show that the yield of N-(4-ethylphenyl)-2,5-dimethyltetrahydropyrrole (3f) obtained in the embodiment of the present invention is 91%.

[0134] Example 29

[0135] The reaction mixture was basically the same as Example 2, except that 4-fluoroaniline, 3 mmol 2,5-hexanediol, and 150 mg 10 wt% Cu-5 wt% Co / α-Al2O3 were used instead of aniline, 0.6 mmol 2,5-hexanediol, and 100 mg 10 wt% Cu-5 wt% Co / α-Al2O3 in Example 2. The test results showed that the yield of N-(4-fluorophenyl)-2,5-dimethyltetrahydropyrrole (3 g) obtained in the embodiment of the present invention was 75%.

[0136] Example 30

[0137] The reaction mixture was basically the same as Example 2, except that 2-isopropylaniline and 200 mg of 10 wt% Cu-5 wt% Co / α-Al2O3 were used instead of aniline and 100 mg of 10 wt% Cu-5 wt% Co / α-Al2O3 in Example 2. The test results showed that the yield of N-(2-isopropylphenyl)-2,5-dimethyltetrahydropyrrole (3h) obtained in the embodiment of the present invention was 96%.

[0138] Example 31

[0139] The reaction was basically the same as Example 2, except that naphthylamine, 3 mmol 2,5-hexanediol, and 150 mg 10 wt% Cu-5 wt% Co / α-Al2O3 were used instead of aniline, 0.6 mmol 2,5-hexanediol, and 100 mg 10 wt% Cu-5 wt% Co / α-Al2O3 in Example 2. The test results showed that the yield of N-naphthyl-2,5-dimethyltetrahydropyrrole (3i) obtained in this embodiment of the present invention was 80%.

[0140] Example 32

[0141] The method is basically the same as Example 2, except that phenylethylamine is used instead of aniline in Example 2. The test results show that the yield of N-phenylethyl-2,5-dimethyltetrahydropyrrole (3j) obtained in the embodiment of the present invention is 96%.

[0142] Example 33

[0143] The method is basically the same as Example 2, except that n-hexylamine is used instead of aniline in Example 2. The test results show that the yield of N-hexyl-2,5-dimethyltetrahydropyrrole (3k) obtained in the embodiment of the present invention is 98%.

[0144] Example 34

[0145] The method is basically the same as Example 2, except that n-octylamine is used instead of aniline in Example 2. The test results show that the yield of N-octyl-2,5-dimethyltetrahydropyrrole (31) obtained in the embodiment of the present invention is 95%.

[0146] Example 35

[0147] The reaction was basically the same as Example 2, except that isooctylamine and 3 mmol 2,5-hexanediol were used instead of aniline and 0.6 mmol 2,5-hexanediol in Example 2. The test results showed that the yield of N-isooctyl-2,5-dimethyltetrahydropyrrole (3m) obtained in the embodiment of the present invention was 95%.

[0148] Example 36

[0149] The reaction was basically the same as Example 2, except that 2 mmol 1,4-pentanediol and 150 mg 10 wt% Cu-5 wt% Co / α-Al2O3 were used instead of 0.6 mmol 2,5-hexanediol and 100 mg 10 wt% Cu-5 wt% Co / α-Al2O3 in Example 2. The test results showed that the yield of N-phenyl-2-methyltetrahydropyrrole (3n) obtained in this embodiment of the present invention was 99%.

[0150] Example 37

[0151] The present invention is basically the same as Example 2, except that 4-methylaniline, 2 mmol 1,4-pentanediol, and 150 mg 10 wt% Cu-5 wt% Co / α-Al2O3 are used instead of aniline, 0.6 mmol 2,5-hexanediol, and 100 mg 10 wt% Cu-5 wt% Co / α-Al2O3 in Example 2. The test results show that the yield of N-(4-methylphenyl)-2-methyltetrahydropyrrole (3o) obtained in this embodiment of the present invention is 80%.

[0152] Example 38

[0153] The method is basically the same as Example 2, except that 4-fluoroaniline, 2 mmol 1,4-pentanediol, and 150 mg 10 wt% Cu-5 wt% Co / α-Al2O3 are used instead of aniline, 0.6 mmol 2,5-hexanediol, and 100 mg 10 wt% Cu-5 wt% Co / α-Al2O3 in Example 2. The test results show that the yield of N-(4-fluorophenyl)-2-methyltetrahydropyrrole (3p) obtained in the embodiment of the present invention is 87%.

[0154] Example 39

[0155] The method is basically the same as Example 2, except that 1 mmol 1,4-butanediol is used instead of 0.6 mmol 2,5-hexanediol in Example 2. The test results show that the yield of N-phenyltetrahydropyrrole (3q) obtained in the embodiment of the present invention is 90%.

[0156] Example 40

[0157] The reaction was basically the same as Example 2, except that 4-methylaniline and 1 mmol 1,4-butanediol were used instead of aniline and 0.6 mmol 2,5-hexanediol in Example 2. The test results showed that the yield of N-(4-methylphenyl)tetrahydropyrrole (3r) obtained in the embodiment of the present invention was 73%.

[0158] Example 41

[0159] The reaction was basically the same as Example 2, except that 4-fluoroaniline and 1 mmol 1,4-butanediol were used instead of aniline and 0.6 mmol 2,5-hexanediol in Example 2. The test results showed that the yield of N-(4-fluorophenyl)tetrahydropyrrole (3s) obtained in the example of the present invention was 84%.

[0160] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the above embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the above embodiments, or replace some or all of the technical features therein with equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for synthesizing a tetrahydropyrrole derivative, characterized in that: The method comprises mixing and reacting an amine represented by Formula 1a with a diol represented by Formula 2a in the presence of a heterogeneous supported bimetallic catalyst and an organic solvent to obtain a tetrahydropyrrole derivative represented by Formula 3a. The reaction formula is as follows: wherein R is selected from one of the following groups: aryl, substituted aryl, alkyl and substituted alkyl; Wherein, R1 and R2 are each independently selected from one of the following groups: hydrogen, alkyl.

2. The synthesis method according to claim 1, wherein The heterogeneous supported bimetallic catalyst is supported by α-Al2O3 and loaded with metals Cu and Co; preferably, the heterogeneous supported bimetallic catalyst is x wt% Cu-y wt% Co / α-Al2O3; More preferably, based on the total weight of the catalyst, x+y=15-20; more preferably, x and y are each independently 3-12.

3. The synthesis method according to claim 1, wherein: The reaction conditions include: reaction temperature of 130-170° C., and reaction time of 4-24 hours.

4. The synthesis method according to claim 1, wherein: The organic solvent is selected from one or more of p-xylene, o-xylene, and m-xylene; and / or, The amount of the organic solvent used is 2 to 4 mL for every 0.5 mmol of amine.

5. The synthesis method according to claim 1, wherein: The amount of the heterogeneous supported bimetallic catalyst added is 50 to 200 mg for every 0.5 mmol of amines.

6. The synthesis method according to claim 1, wherein: The molar ratio of the diols to the amines is 1-6:

1.

7. The synthesis method according to claim 1, wherein: R is independently selected from one of the following groups: phenyl, 4-methylphenyl, 2-methylphenyl, 4-methoxyphenyl, 4-ester phenyl, 4-acetophenone, 4-fluorophenyl, 2-isopropylphenyl, naphthyl, phenethyl, isooctyl, hexyl, octyl; R1 is selected from one of the following groups: hydrogen, methyl; R2 is selected from one of the following groups: hydrogen, methyl.

8. The synthesis method according to claim 1, wherein: The amines are selected from one or more of aniline, 4-methylaniline, 2-methylaniline, 4-methoxyaniline, methyl 4-aminobenzoate, 4-aminoacetophenone, 4-fluoroaniline, 2-isopropylaniline, naphthylamine, phenethylamine, isooctylamine, hexylamine, and octylamine.

9. The synthesis method according to claim 1, wherein: The diols are selected from one or more of 1,4-butanediol, 1,5-pentanediol, and 2,5-hexanediol.

10. A tetrahydropyrrole derivative synthesized according to the method of any one of claims 1 to 9.

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