Pyrrole derivative and synthesis method thereof

Abstract

The invention discloses a pyrrole derivative and a synthesis method thereof. The synthesis method of the pyrrole derivative comprises the following steps: in the presence of a heterogeneous supported bimetallic catalyst, an organic solvent and a dehydrogenation agent, mixing amines and dihydric alcohols, and reacting to prepare the pyrrole derivative. The synthesis method disclosed by the invention is novel, the catalyst is a non-noble metal bimetallic solid catalyst, the yield of the product can be remarkably improved, and the catalyst is convenient to recycle; the diol raw material used in the invention is wide in source and low in price; the reaction does not need alkaline additives, so that the requirements on reaction equipment are reduced, and the method has the characteristics of greenness, sustainability and the like.

Description

Technical Field

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

[0002] Pyrrole derivatives (N-substituted pyrrole compounds) are important components of heterocyclic compounds and are crucial building blocks for many natural products, pharmaceuticals, and agrochemicals. They possess potent biological activities, including antibacterial, antitumor, and antifungal properties. The synthesis of pyrrole derivatives has long been primarily based on the Hantzsch, Knorr, and Paal-Knorr strategies. However, these strategies typically require the use of halogenated reagents and strong base additives, and the three-component reaction system is complex, with harsh reaction conditions and limited compatibility with sensitive groups, thus limiting their synthetic applications.

[0003] Diols are a commodity chemical, widely used in fields such as synthetic chemistry and polymer chemistry. They are also readily available from fossil and natural biomass resources. Furthermore, the production of C2-C6 diols from biomass has been highly successful, including ethylene glycol, 1,3-propylene glycol, 1,4-butanediol, 2,5-hexanediol, and 1,3-hexanediol. Using these diols as raw materials, through reactions such as dehydrogenation and cyclization, bio-based pyrrole compounds can be constructed, providing a new approach for the development of green pyrrole synthesis.

[0004] Regarding the synthesis of pyrrole compounds from dihydric fatty alcohols and organic amines, Milstein et al. used homogeneous PNNH-Co as a catalyst and tBuOK as a base additive to synthesize a series of N-alkyl-2,5-methylpyrrole compounds (at 150°C) from 2,5-hexanediol and fatty amines with yields ranging from 56% to 93% (Nat. Chem., 2013, 5, 140-144). Subsequently, they reported a method for preparing N-substituted-2,5-dimethylpyrrole compounds from 2,5-hexanediol and NH3 using an acridinyl-ruthenium pincer complex as a catalyst (Angew. Chem. Int. Ed., 2016, 55, 14373). Sepelgy et al. use 1,4-butanediol or 2,5-hexanediol and aliphatic amine as raw materials, and under the common catalysis of Mn-PNP complex and K2CO3, produce a series of pyrrole compounds with different structures (J Am.Chem.Soc., 2018, 140, 11931). However, the above reaction system is a homogeneous metal catalysis system, and it is necessary to add a strong base additive, and there are problems such as environmental pollution risk and catalyst separation difficulty. Therefore, it is very necessary to develop a new solid catalyst to realize the synthesis of pyrrole compounds by diols and organic amines under mild conditions.

[0005] In view of this, the present invention is proposed. Summary of the Invention

[0006] The catalytic efficiency of the existing technology needs to be improved, and a strong base additive needs to be added, which has the problems of environmental pollution risk and difficulty in separating the catalyst. The present invention designs and provides a new method for the synthesis of pyrrole derivatives and the synthesis of the same. The method uses biomass-based diols and organic amines as raw materials, designs a heterogeneous supported bimetallic catalytic system, adds a hydrogen scavenger, and realizes the synthesis of pyrrole derivatives by receptor-free dehydrogenation-coupling reaction of biomass-based diols and organic amines, obtaining a high yield. The supported bimetallic catalyst in this reaction system has simple synthesis steps, good stability, high substrate compatibility, and can still exert a good catalytic effect without adding a strong base. The development of this method will provide a new solution for constructing a green and sustainable synthesis of pyrrole derivatives.

[0007] In order to achieve the above-mentioned object of the present invention, the first aspect of the present invention provides a method for synthesizing pyrrole derivatives, comprising reacting an amine represented by formula 1a with a pyrrole derivative in the presence of a heterogeneous supported bimetallic catalyst, an organic solvent, and a hydrogen scavenger.

[0008] The diols shown in formula 2a are mixed and reacted to prepare the pyrrole derivative shown in formula 3a, and the reaction formula is as follows:

[0009]

[0010] wherein R is selected from one of the following groups: aryl, substituted aryl, alkyl and substituted alkyl;

[0011] Wherein, R1 and R2 are each independently selected from one of the following groups: hydrogen, alkyl.

[0012] According to some embodiments of the present invention, the heterogeneous supported bimetallic catalyst is supported on γ-Al2O3 and loaded with metal Cu and Co; more preferably, the heterogeneous supported bimetallic catalyst is x wt% Cu-ywt% Co / γ-Al2O3, wherein wt% refers to weight percentage; x wt% Cu means that the weight proportion of Cu in the total catalyst is x weight%; y wt% Co means that the weight proportion of Co in the total catalyst is y weight%.

[0013] According to some embodiments of the present invention, x+y=15-20, which means that the total loading amount of Cu and Co is 15 wt%-20 wt%.

[0014] 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%. In other words, 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 catalysts include, but are not limited to: 5 wt% Cu-10 wt% Co / γ-Al2O3, 10 wt% Cu-5 wt% Co / γ-Al2O3, and 12 wt% Cu-5 wt% Co / γ-Al2O3.

[0015] 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:

[0016] 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.

[0017] 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.

[0018] According to some embodiments of the present invention, the organic solvent is selected from one or more of p-xylene, o-xylene, m-xylene, n-pentane, n-octane, and dodecane.

[0019] 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.

[0020] According to some embodiments of the present invention, the hydrogen scavenger is selected from one or more of styrene, cyclohexene, and cyclopentene.

[0021] According to some embodiments of the present invention, the amount of the hydrogen scavenger is 1 to 5 mmol per 0.5 mmol of amine, for example but not limited to, the amount of the hydrogen scavenger is 1 mmol, 1.5 mmol, 2 mmol, 2.5 mmol, 3 mmol, 3.5 mmol, 4 mmol, 4.5 mmol, or 5 mmol per 0.5 mmol of amine.

[0022] 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-methanesulfonylaniline, 4-fluoroaniline, 2-isopropylaniline, naphthylamine, phenethylamine, 4-methylphenethylamine, hexylamine, and octylamine.

[0023] According to some embodiments of the present invention, the dosage of the heterogeneously supported bimetallic catalyst is 50-120 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, or 120 mg per 0.5 mmol of amine.

[0024] According to some embodiments of the present invention, the diols are selected from but not limited to: one or more of 1,4-butanediol, 1,5-pentanediol, 2,5-hexanediol

[0025] According to some embodiments of the present invention, the molar ratio of the diols to the amines is 1-2:1, for example but not limited to 1:1, 1.2:1, 1.4:1, 1.6:1, 1.8:1, and 2:1.

[0026] According to some embodiments of the present invention, R is selected from one of the following groups: phenyl, 4-methylphenyl, 2-methylphenyl, 4-methoxyphenyl, 4-esterphenyl, 4-methanesulfonylphenyl, 4-fluorophenyl, 2-isopropylphenyl, naphthyl, phenethyl, 4-methylphenethyl, hexyl, and octyl.

[0027] According to some embodiments of the present invention, R1 is selected from one of the following groups: hydrogen, methyl.

[0028] According to some embodiments of the present invention, R2 is selected from one of the following groups: hydrogen, methyl.

[0029] According to some embodiments of the present invention, the synthesis method does not require the addition of a strong base.

[0030] The second aspect of the present invention provides a pyrrole derivative synthesized by the above method.

[0031] Beneficial effects of the present invention

[0032] (1) The present invention is the first to use biomass-based diols as raw materials to undergo receptor-free dehydrogenation-coupling reaction with organic amines to obtain high-yield pyrrole derivatives, with the only by-product being water, which is a breakthrough in the industry.

[0033] (2) In the present invention, the synthesis of pyrrole 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.

[0034] (3) Compared with previous studies, the heterogeneous supported bimetallic catalytic system involved in the present invention has realized the synthesis of diols and pyrroles catalyzed by heterogeneous catalysts for the first time, with a wide substrate range and high yield. This invention is a good supplement and beneficial improvement to the existing pyrrole derivative synthesis system. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] 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. 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.

[0036] Figure 1 This is the H NMR spectrum of the product obtained in Example 2 of the present invention.

[0037] Figure 2 The C NMR spectrum of the product obtained in Example 2 of the present invention is shown in FIG.

[0038] Figure 3 This is a scanning electron microscope (SEM) image of the 10wt% Cu-5wt% Co / γ-Al2O3 support used in Example 1 of the present invention.

[0039] Figure 4 This is a transmission electron microscope (TEM) image of the 10wt% Cu-5wt% Co / γ-Al2O3 catalyst synthesized in Example 1 of the present invention. DETAILED DESCRIPTION

[0040] The technical solutions of the present invention are described clearly and completely below with reference to the embodiments. It is obvious that the embodiments described are only a portion of the embodiments of the present invention, not all of them. All other embodiments derived by persons of ordinary skill in the art based on the embodiments of the present invention without creative effort are also within the scope of protection of the present invention.

[0041] 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.

[0042] Example 1

[0043] The 10wt% Cu-5wt% Co / γ-Al2O3 bimetallic catalyst was prepared by an impregnation method, comprising the following steps:

[0044] First, 1.7g of commercially available γ-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 the mixture was stirred at 750r / min at room temperature for 12h. Then, a rotary evaporator was used to remove moisture at 40°C. The obtained solid was dried in an oven at 110°C for 12h, and then ground with a mortar while hot. The obtained powder was calcined at 400°C in a muffle furnace for 4h, and then taken out after cooling to room temperature. Finally, it was reduced in a tube furnace at 500°C under 20% H2 / N2 for 3h, and naturally cooled to room temperature and taken out to obtain a 10wt% Cu-5wt% Co / γ-Al2O3 catalyst. The structural characterization of the obtained catalyst is shown in Figure 2. Figure 3 and 4 As shown. Figure 3 It was found that the catalyst surface showed a flower-like structure and was slightly disordered. Figure 4 It was found that the metal nanoparticles were uniformly dispersed with an average particle size of 3.92 nm, proving that the metal Cu and Co were successfully loaded and evenly distributed on the support surface.

[0045] Example 2

[0046] 100 mg of 10 wt% Cu-5 wt% Co / γ-Al2O3 (Example 1), 0.5 mmol aniline, 0.6 mmol 2,5-hexanediol, 3 mmol styrene 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 12 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-dimethylpyrrole. Using naphthalene as the internal standard, quantitative analysis by gas chromatography revealed a 99% yield of N-phenyl-2,5-dimethylpyrrole. The yield was calculated as follows: Target product yield (%) = actual amount of target product obtained / theoretical amount of target product.

[0047] Comparative Example 1

[0048] 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 / γ-Al203 in Example 2. The test results show that the yield of N-phenyl-2,5-dimethylpyrrole obtained in this example is only 37%.

[0049] The preparation method of the 10 wt % Cu-5 wt % Co / TiO 2 used is the same as that of Example 1, except that commercially available TiO 2 is used instead of γ-Al 2 O 3 .

[0050] Comparative Example 2

[0051] 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 / γ-Al2O3 in Example 2. The test results show that the yield of N-phenyl-2,5-dimethylpyrrole obtained in this example is 42%.

[0052] The preparation method of the 10 wt % Cu-5 wt % Co / ZrO 2 used is the same as that in Example 1, except that commercially available ZrO 2 is used instead of γ-Al 2 O 3 .

[0053] Comparative Example 3

[0054] 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 / γ-Al2O3 in Example 2. The test results show that the yield of N-phenyl-2,5-dimethylpyrrole obtained in this example of the present invention is 13%.

[0055] The preparation method of the 10 wt % Cu-5 wt % Co / MgO used is the same as that of Example 1, except that commercially available MgO is used instead of γ-Al 2 O 3 .

[0056] Comparative Example 4

[0057] The reaction 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 / γ-Al2O3 in Example 2. The test results showed that the yield of N-phenyl-2,5-dimethylpyrrole obtained in this example was 17%.

[0058] The preparation method of the 10 wt % Cu-5 wt % Co / MgAl-LDO used was the same as that in Example 1, except that commercially available MgAl-LDO was used instead of γ-Al 2 O 3 .

[0059] Comparative Example 5

[0060] It is basically the same as Example 2, except that 15wt% Cu / γ-Al2O3 is used instead of 10wt% Cu-5wt% Co / γ-Al2O3 in Example 2. The test results show that the yield of N-phenyl-2,5-dimethylpyrrole obtained in this example is 26%.

[0061] Comparative Example 6

[0062] It is basically the same as Example 2, except that 15wt% Co / γ-Al2O3 is used instead of 10wt% Cu-5wt% Co / γ-Al2O3 in Example 2. The test results show that the yield of N-phenyl-2,5-dimethylpyrrole obtained in this example is 5%.

[0063] Comparative Example 7

[0064] It is basically the same as Example 2, except that 10wt% Cu-5wt% Ni / γ-Al2O3 is used instead of 10wt% Cu-5wt% Co / γ-Al2O3 in Example 2. The test results show that the yield of N-phenyl-2,5-dimethylpyrrole obtained in this example is 38%.

[0065] Comparative Example 8

[0066] It is basically the same as Example 2, except that 10wt% Cu-5wt% Fe / γ-Al2O3 is used instead of 10wt% Cu-5wt% Co / γ-Al2O3 in Example 2. The test results show that the yield of N-phenyl-2,5-dimethylpyrrole obtained in this example is 51%.

[0067] Comparative Example 9

[0068] It is basically the same as Example 2, except that 10wt% Cu-5wt% Cr / γ-Al2O3 is used instead of 10wt% Cu-5wt% Co / γ-Al2O3 in Example 2. The test results show that the yield of N-phenyl-2,5-dimethylpyrrole obtained in this example is 55%.

[0069] Comparative Example 10

[0070] It is basically the same as Example 2, except that 10wt% Cu-5wt% Pd / γ-Al2O3 is used instead of 10wt% Cu-5wt% Co / γ-Al2O3 in Example 2. The test results show that the yield of N-phenyl-2,5-dimethylpyrrole obtained in this example is 50%.

[0071] The above comparison shows that the catalyst with the best catalytic effect is the Cu-Co / γ-Al2O3 catalyst.

[0072] Proportions of different metals:

[0073] Example 3

[0074] It is basically the same as Example 2, except that 12wt% Cu-3wt% Co / γ-Al2O3 is used instead of 10wt% Cu-5wt% Co / γ-Al2O3 in Example 2. The test results show that the yield of N-phenyl-2,5-dimethylpyrrole obtained in this example is 75%.

[0075] Example 4

[0076] It is basically the same as Example 2, except that 5wt% Cu-10wt% Co / γ-Al2O3 is used instead of 10wt% Cu-5wt% Co / γ-Al2O3 in Example 2. The test results show that the yield of N-phenyl-2,5-dimethylpyrrole obtained in this example is 72%.

[0077] Example 5

[0078] It is basically the same as Example 2, except that 3wt% Cu-12wt% Co / γ-Al2O3 is used instead of 10wt% Cu-5wt% Co / γ-Al2O3 in Example 2. The test results show that the yield of N-phenyl-2,5-dimethylpyrrole obtained in this example is 70%.

[0079] Example 6

[0080] It is basically the same as Example 2, except that 8wt% Cu-12wt% Co / γ-Al2O3 is used instead of 10wt% Cu-5wt% Co / γ-Al2O3 in Example 2. The test results show that the yield of N-phenyl-2,5-dimethylpyrrole obtained in this example is 79%.

[0081] Example 7

[0082] It is basically the same as Example 2, except that 10t% Cu-10wt% Co / γ-Al2O3 is used instead of 10wt% Cu-5wt% Co / γ-Al2O3 in Example 2. The test results show that the yield of N-phenyl-2,5-dimethylpyrrole obtained in this example is 82%.

[0083] 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%.

[0084] Different catalyst dosage:

[0085] Example 8

[0086] The method is basically the same as Example 2, except that 120 mg of 10 wt% Cu-5 wt% Co / γ-Al2O3 catalyst is used instead of 100 mg of 10 wt% Cu-5 wt% Co / γ-Al2O3 in Example 2. The test results show that the yield of N-phenyl-2,5-dimethylpyrrole obtained in this example is 99%.

[0087] Example 9

[0088] The method is basically the same as Example 2, except that 75 mg of 10 wt% Cu-5 wt% Co / γ-Al2O3 catalyst is used instead of 100 mg of 10 wt% Cu-5 wt% Co / γ-Al2O3 in Example 2. The test results show that the yield of N-phenyl-2,5-dimethylpyrrole obtained in this example is 88%.

[0089] Example 10

[0090] The method is basically the same as Example 2, except that 50 mg of 10 wt% Cu-5 wt% Co / γ-Al2O3 catalyst is used instead of 100 mg of 10 wt% Cu-5 wt% Co / γ-Al2O3 in Example 2. The test results show that the yield of N-phenyl-2,5-dimethylpyrrole obtained in this example is 75%.

[0091] The above examples show that the present catalytic system can achieve excellent catalytic effects when the catalyst dosage is 50-120 mg.

[0092] Different reaction temperatures:

[0093] Example 11

[0094] 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-dimethylpyrrole obtained in this example is 71%.

[0095] Example 12

[0096] 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-dimethylpyrrole obtained in this example is 80%.

[0097] Example 13

[0098] 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-dimethylpyrrole obtained in this example is 91%.

[0099] Example 14

[0100] 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-dimethylpyrrole obtained in this example is 89%.

[0101] The above examples show that the catalytic system can achieve excellent catalytic effects when the reaction temperature is 130-170°C.

[0102] Different reaction times:

[0103] Example 15

[0104] The method is basically the same as Example 2, except that 4 hours is used instead of 12 hours in Example 2. The test results show that the yield of N-phenyl-2,5-dimethylpyrrole obtained in the embodiment of the present invention is 85%.

[0105] Example 16

[0106] The method is basically the same as Example 2, except that 8 hours is used instead of 12 hours in Example 2. The test results show that the yield of N-phenyl-2,5-dimethylpyrrole obtained in the embodiment of the present invention is 90%.

[0107] Example 17

[0108] The method is basically the same as Example 2, except that 16 hours is used instead of 12 hours in Example 2. The test results show that the yield of N-phenyl-2,5-dimethylpyrrole obtained in the embodiment of the present invention is 95%.

[0109] Example 18

[0110] The method is basically the same as Example 2, except that 20 h is used instead of 12 h in Example 2. The test results show that the yield of N-phenyl-2,5-dimethylpyrrole obtained in the embodiment of the present invention is 85%.

[0111] Example 19

[0112] The method is basically the same as Example 2, except that 24 hours is used instead of 12 hours in Example 2. The test results show that the yield of N-phenyl-2,5-dimethylpyrrole obtained in the embodiment of the present invention is 79%.

[0113] The above examples show that the catalytic system can achieve excellent catalytic effects when the reaction time is 4-24 hours.

[0114] Different dehydrogenation agents and dosage:

[0115] Example 20

[0116] The method is basically the same as Example 2, except that 3 mmol of cyclohexene is used instead of 3 mmol of styrene in Example 2. The test results show that the yield of N-phenyl-2,5-dimethylpyrrole obtained in this example is 85%.

[0117] Example 21

[0118] The method is basically the same as Example 2, except that 3 mmol of cyclopentene is used instead of 3 mmol of styrene in Example 2. The test results show that the yield of N-phenyl-2,5-dimethylpyrrole obtained in this example is 81%.

[0119] Example 22

[0120] The method is basically the same as Example 2, except that 1 mmol of styrene is used instead of 3 mmol of styrene in Example 2. The test results show that the yield of N-phenyl-2,5-dimethylpyrrole obtained in this example is 90%.

[0121] Example 23

[0122] The method is basically the same as Example 2, except that 2 mmol of styrene is used instead of 3 mmol of styrene in Example 2. The test results show that the yield of N-phenyl-2,5-dimethylpyrrole obtained in this example is 95%.

[0123] Example 24

[0124] The method is basically the same as Example 2, except that 4 mmol of styrene is used instead of 3 mmol of styrene in Example 2. The test results show that the yield of N-phenyl-2,5-dimethylpyrrole obtained in this example is 99%.

[0125] Example 25

[0126] The method is basically the same as Example 2, except that 5 mmol of styrene is used instead of 3 mmol of styrene in Example 2. The test results show that the yield of N-phenyl-2,5-dimethylpyrrole obtained in this example is 99%.

[0127] The above examples show that the present catalytic system can achieve excellent catalytic effects when 1 to 5 mmol of styrene and other unsaturated compounds (cyclohexene, cyclopentene) are used as hydrogen scavengers.

[0128] Different solvents and dosage:

[0129] Example 26

[0130] 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-dimethylpyrrole obtained in this example is 92%.

[0131] Example 27

[0132] 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-dimethylpyrrole obtained in this example is 95%.

[0133] Example 28

[0134] The method is basically the same as Example 2, except that 3 mL of n-pentane is used instead of 3 mL of p-xylene in Example 2. The test results show that the yield of N-phenyl-2,5-dimethylpyrrole obtained in this example is 80%.

[0135] Example 29

[0136] The method is basically the same as Example 2, except that 3 mL of n-octane is used instead of 3 mL of p-xylene in Example 2. The test results show that the yield of N-phenyl-2,5-dimethylpyrrole obtained in this example is 78%.

[0137] Example 30

[0138] 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-dimethylpyrrole obtained in this example is 75%.

[0139] Example 31

[0140] 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-dimethylpyrrole obtained in this example is 95%.

[0141] Example 32

[0142] 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-dimethylpyrrole obtained in this example is 90%.

[0143] 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, n-pentane, n-octane, and n-dodecane).

[0144] Amine and diol substrate expansion:

[0145] Structure table of different pyrrole derivatives

[0146]

[0147] Example 33

[0148] The method is basically the same as Example 2, except that 4-methylaniline is used instead of aniline in Example 2. The test results show that the yield of N-(4-methylphenyl)-2,5-dimethylpyrrole (3b) obtained in the embodiment of the present invention is 99%.

[0149] Example 34

[0150] The method is basically the same as Example 2, except that 2-methylaniline is used instead of aniline in Example 2. The test results show that the yield of N-(2-methylphenyl)-2,5-dimethylpyrrole (3c) obtained in the embodiment of the present invention is 99%.

[0151] Example 35

[0152] The reaction was basically the same as Example 2, except that 4-methoxyaniline, 120 mg of catalyst, and 24 h were used instead of aniline, 100 mg of catalyst, and 12 h in Example 2. The test results showed that the yield of N-(4-methoxyphenyl)-2,5-dimethylpyrrole (3d) obtained in the embodiment of the present invention was 95%.

[0153] Example 36

[0154] The reaction mixture was basically the same as Example 2, except that 4-aminobenzoic acid methyl ester and 24h were used instead of aniline and 12h in Example 2. The test results showed that the yield of N-(4-benzoic acid methyl ester)-2,5-dimethylpyrrole (3e) obtained in the embodiment of the present invention was 99%.

[0155] Example 37

[0156] The method is basically the same as Example 2, except that 4-methanesulfonylaniline is used instead of aniline in Example 2. The test results show that the yield of N-(4-methanesulfonylphenyl)-2,5-dimethylpyrrole (3f) obtained in the embodiment of the present invention is 91%.

[0157] Example 38

[0158] The method is basically the same as Example 2, except that 4-fluoroaniline is used instead of aniline in Example 2. The test results show that the yield of N-(4-fluorophenyl)-2,5-dimethylpyrrole (3 g) obtained in the embodiment of the present invention is 99%.

[0159] Example 39

[0160] The reaction mixture was basically the same as Example 2, except that 2-isopropylaniline, 5 mmol styrene, and 72 h were used instead of aniline, 3 mmol styrene, and 12 h in Example 2. The test results showed that the yield of N-(2-isopropylphenyl)-2,5-dimethylpyrrolidine obtained in the embodiment of the present invention was 86%.

[0161] Example 40

[0162] The method is basically the same as Example 2, except that naphthylamine and 24h are used instead of aniline and 12h in Example 2. The test results show that the yield of N-naphthyl-2,5-dimethylpyrrole (3i) obtained in the embodiment of the present invention is 98%.

[0163] Example 41

[0164] The reaction was basically the same as Example 2, except that phenylethylamine, 5 mmol styrene, and 4 h were used instead of aniline, 3 mmol styrene, and 12 h in Example 2. The test results showed that the yield of N-phenylethyl-2,5-dimethylpyrrole (3j) obtained in the embodiment of the present invention was 82%.

[0165] Example 42

[0166] The reaction was basically the same as Example 2, except that 4-methylphenylethylamine, 5 mmol styrene, and 4 h were used instead of aniline, 3 mmol styrene, and 12 h in Example 2. The test results showed that the yield of N-(4-methylphenyl)-2,5-dimethylpyrrole (3k) obtained in the embodiment of the present invention was 75%.

[0167] Example 43

[0168] The reaction mixture was basically the same as Example 2, except that n-octylamine, 5 mmol styrene, and 8 h were used instead of aniline, 3 mmol styrene, and 12 h in Example 2. The test results showed that the yield of N-octyl-2,5-dimethylpyrrole (3l) obtained in the embodiment of the present invention was 91%.

[0169] Example 44

[0170] The reaction mixture was basically the same as Example 2, except that n-hexylamine, 5 mmol styrene, and 4 h were used instead of aniline, 3 mmol styrene, and 12 h in Example 2. The test results showed that the yield of N-hexyl-2,5-dimethylpyrrole (3 m) obtained in the embodiment of the present invention was 87%.

[0171] Example 45

[0172] The reaction was basically the same as Example 2, except that 1,4-pentanediol, 6 mmol styrene, and 24 h were used instead of 2,5-hexanediol, 3 mmol styrene, and 12 h in Example 2. The test results showed that the yield of N-phenyl-2-methylpyrrole (3n) obtained in the embodiment of the present invention was 79%.

[0173] Example 46

[0174] The reaction was basically the same as Example 2, except that 1,4-pentanediol, 4-methylaniline, 6 mmol styrene, and 24 h were used instead of 2,5-hexanediol, aniline, 3 mmol styrene, and 12 h in Example 2. The test results showed that the yield of N-(4-methylphenyl)-2-methylpyrrole (3o) obtained in the embodiment of the present invention was 81%.

[0175] Example 47

[0176] The reaction was basically the same as Example 2, except that 1,4-pentanediol, 4-fluoroaniline, 6 mmol styrene, and 24 h were used instead of 2,5-hexanediol, aniline, 3 mmol styrene, and 12 h in Example 2. The test results showed that the yield of N-(4-fluorophenyl)-2-methylpyrrole (3p) obtained in the embodiment of the present invention was 75%.

[0177] 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 pyrrole 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, an organic solvent, and a hydrogen scavenger to obtain a pyrrole 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, characterized in that The heterogeneous supported bimetallic catalyst is supported by γ-Al2O3 and loaded with metals Cu and Co; preferably, the heterogeneous supported bimetallic catalyst is x wt% Cu-y wt% Co / γ-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, m-xylene, n-pentane, n-octane, and dodecane; 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 dehydrogenating agent is selected from one or more of styrene, cyclohexene, and cyclopentene; and / or, The amount of the hydrogen scavenger used is 1 to 5 mmol relative to every 0.5 mmol of amines.

6. The synthesis method according to claim 1, wherein: The amines are selected from one or more of aniline, 4-methylaniline, 2-methylaniline, 4-methoxyaniline, 4-aminobenzoic acid methyl ester, 4-methanesulfonylaniline, 4-fluoroaniline, 2-isopropylaniline, naphthylamine, phenethylamine, 4-methylphenethylamine, hexylamine, and octylamine; and / or, The amount of the heterogeneous supported bimetallic catalyst added is 50 to 120 mg for every 0.5 mmol of amines.

7. 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.

8. The synthesis method according to claim 1, wherein: The molar ratio of the diols to the amines is 1-2:

1.

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

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

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