A method and catalyst for sustainable preparation of pyrrole compounds

Abstract

The present invention provides a method and catalyst for preparing pyrrole compounds in a green and sustainable manner. The pyrrole compounds are prepared by dehydrogenation and cross-condensation of alcohol molecules and 2-amino alcohol molecules, wherein the alcohol molecules include ethanol, propanol, isopropanol, butanol and high-carbon fatty alcohols, and the amino alcohols include 2-aminoethanol and substituted 2-amino alcohols. The catalyst is composed of composite oxide-supported metal nanoparticles, wherein the metal nanoparticles are mainly composed of one or more of Ni, Co and Cu; the composite oxide is composed of two or three of nickel oxide, cobalt oxide, magnesium oxide, aluminum oxide, zinc oxide and zirconium oxide. The catalyst realizes the preparation of pyrrole compounds by alcohol molecules and 2-amino alcohol molecules for the first time without the addition of an alkali, and the yield can reach up to 99%.

Description

Technical Field

[0001] The invention relates to the fields of chemistry, chemical engineering and catalysts, and in particular to a method for preparing pyrrole compounds by dehydrogenation and cross-condensation of alcohol molecules and 2-amino alcohol molecules with high efficiency and a catalyst thereof. Background Art

[0002] As a very important five-membered nitrogen-containing heterocyclic compound, pyrroles are widely used in the medical field due to their anti-tumor and bactericidal biological activities. For example, they are used as the key to synthesizing the drug molecules sumatinib and atorvastatin for the treatment of gastric cancer and hypercholesterolemia. Pyrrole is also an important structural unit of chlorophyll in green plants and heme in human hemoglobin. Polypyrrole with pyrrole as a monomer is used as a high molecular conductive polymer in batteries and capacitor materials. Therefore, it is of great significance and value to explore the green and sustainable preparation of pyrrole compounds.

[0003] In industry, the earliest industrial production method of pyrrole is to use Pd, Ru and other catalysts to react 1,4-butynediol with ammonia to prepare it, with a yield of more than 65%. Later, MoO x , VO x The preparation of pyrrole from furan catalyzed by acidic oxides and the preparation of pyrrole from pyrrolidine catalyzed by Pd or Rh-based catalysts are also common processes. The traditional industrial route for preparing pyrrole compounds mainly involves the raw materials coming from petrochemicals, requiring high temperature and pressure, harsh reaction conditions, and using high-loaded precious metals as active centers, resulting in high catalyst costs.

[0004] In laboratory preparation, the synthesis methods of pyrrole are mainly divided into the Knorr reaction of α-halomethyl ketone, β-ketoester and ammonia condensation, the Paal-Knorr reaction of 1,4-diketone and primary amine or ammonia condensation, the Barton-Zard reaction of nitroolefin and α-isocyanoacetate under alkaline conditions to obtain pyrrole ring derivatives, and the Hantzsch reaction of α-aminoketone and carbonyl condensation with electron-withdrawing group at α position. Among these numerous pyrrole synthesis methods, the reaction conditions often require the participation of an equivalent amount of strong acid / base, accompanied by the generation of halides that are more harmful to the environment, and the need to synthesize specific reaction substrates in advance. Therefore, it is of great scientific significance and industrial value to develop a green and sustainable preparation method for pyrrole compounds without the need for external strong acid / base, using renewable, cheap and readily available reaction substrates.

[0005] In 2013, Kempe et al. first reported an Ir-PNP complex that catalyzed the reaction of aromatic and aliphatic secondary alcohols with substituted 2-aminoethanol to produce 1,4-disubstituted pyrrole compounds in the presence of 1.1 equiv. KOtBu, with a yield of 42-97%. Subsequently, Saito's group reported the use of *CpRuCl(PPh3)2 as a catalyst to catalyze the reaction of aromatic and aliphatic secondary alcohols with substituted 2-amino alcohols to produce pyrrole compounds in the presence of 10 mol% KOtBu, with a yield of 59-89%. Later, the use of RuHCl(CO)(PPh3)3 and [(OC5H3N-CO-C5H3N-C5H4N)Ru(PPh3)2(CO)]Cl was gradually developed. - Catalyst, but the substrate is still limited to the reaction of aromatic and aliphatic secondary alcohols with substituted 2-amino alcohols, and an external strong organic base KOtBu is also required, otherwise pyrrole compounds cannot be obtained. In 2016, Milstein et al. reported Co-PNN pincer chelate, which catalyzed the reaction of aliphatic secondary diols with aromatic and aliphatic long-chain primary amines to synthesize N-substituted 1,4-disubstituted pyrrole compounds under 5mol% KOtBu conditions, with a yield of 22-93%. It is worth noting that 1,4-butanediol can also undergo this reaction, but there is only one case of primary diols, and the reaction of other primary diols has not been reported. Subsequently, in 2019, Banerjee's team reported the formation of a complex with NiBr2 and phenanthroline ligands, and catalyzed the reaction of aromatic secondary alcohols with substituted 2-aminoethanol in the presence of 1.0equiv.KOtBu to produce 1,4-disubstituted pyrrole compounds with a yield of 31-60%. In 2014, Kempe et al. reported the first heterogeneous catalytic synthesis of pyrrole compounds, using equivalent KOtBu and 1.27wt% Ir / SiCN to catalyze the synthesis of pyrrole compounds from aromatic and aliphatic secondary alcohols and substituted 2-amino alcohols, with a yield of up to 90%. In 2016, Shimizu used equivalent KOtBu and 5wt% Pt / C to catalyze the synthesis of pyrrole from alcohols and amino alcohols, and obtained a yield of 92%, but the substrate was limited to the reaction of secondary alcohols and substituted 2-amino alcohols.

[0006] However, in the synthesis of pyrrole compounds reported in existing literature, the substrates are limited to the reaction of aromatic and aliphatic secondary alcohols with substituted 2-amino alcohols, while it is difficult to achieve aromatic or aliphatic primary alcohols derived from green and renewable biomass resources, such as ethanol, propanol, butanol, furanol, and aromatic alcohols. In addition, the existing system requires the addition of an equivalent amount of organic strong base KOtBu, the reaction conditions are harsh, the production equipment requirements are high, and the product separation and purification are complex and difficult. The development of biomass-derived primary alcohols to prepare pyrrole compounds is a green and sustainable process with great research value and industrial value. Summary of the invention

[0007] The present invention provides a green and sustainable method for preparing pyrrole compounds, and the route is shown in Formula I. The pyrrole compounds are prepared by dehydrogenation and cross-condensation of biomass-derived alcohols and 2-amino alcohol molecules with high selectivity, and the yield of the pyrrole compounds can reach up to 99%. The alcohol molecules include ethanol, propanol, isopropanol, butanol and high-carbon fatty alcohols, and the amino alcohols include 2-aminoethanol and substituted 2-amino alcohols.

[0008]

[0009] The technical solution of the present invention is as follows:

[0010] The catalytic reaction is carried out under a certain temperature, pressure and atmosphere, by adding a certain amount of alcohol molecules, 2-amino alcohol molecules and a certain amount of catalyst into a certain type of reactor, reacting for a period of time, cooling after the reaction is completed, taking a certain amount of product, and determining the yield of the pyrrole compound by gas chromatography and nuclear magnetic resonance spectroscopy analysis.

[0011] Furthermore, the R1 and R2 groups in the alcohol molecule can be composed of one or more of H, methyl, ethyl, propyl, phenyl, furyl and the like.

[0012] Furthermore, the R3 and R4 groups of the 2-amino alcohol molecule can be composed of one or more of H, methyl, ethyl, propyl, phenyl, furyl and the like.

[0013] Furthermore, the selected reactor is one of a glass tube reactor, a stainless steel reactor with a polytetrafluoroethylene lining, and a fixed bed reactor.

[0014] Furthermore, the molar ratio of the alcohol molecules to the 2-amino alcohol molecules is (2-100):1.

[0015] Furthermore, the selected reaction temperature is 50-250°C.

[0016] Furthermore, the selected reaction pressure is 0.1-2.0 MPa.

[0017] Furthermore, the selected reaction atmosphere is one of air, nitrogen, argon, etc.

[0018] Furthermore, the reaction time is 0.5-30h.

[0019] Furthermore, the added amount of the catalyst is 1-90% of the molar number of 2-amino alcohol molecules.

[0020] Furthermore, the catalyst is composed of composite oxide-supported metal nanoparticles, the metal nanoparticles are composed of one or more of Ni, Co, and Cu, and the composite oxide is composed of one or more of nickel oxide, cobalt oxide, copper oxide, magnesium oxide, aluminum oxide, iron oxide, zinc oxide, and zirconium oxide, wherein:

[0021] The loading amount of the metal nanoparticles is 5-30% based on the mass of the composite oxide.

[0022] Furthermore, the preparation method of the catalyst comprises the following steps:

[0023] Step 1) Preparation of composite metal oxide

[0024] Precipitating and calcining two or more of a divalent metal, a trivalent metal, and a tetravalent metal to form a composite metal oxide;

[0025] Step 2) Reduction of composite metal oxides

[0026] The composite metal oxide is reduced to obtain metal nanoparticles supported by the composite oxide, namely the catalyst.

[0027] Furthermore, in step 1), the divalent metal is one or more of Ni, Co, Cu, Mg, and Zn.

[0028] Furthermore, in step 1), the trivalent metal is one or two of Al and Fe.

[0029] Furthermore, in step 1), the tetravalent metal is one or two of Zr and Ga.

[0030] Furthermore, in step 1), the molar ratio of the divalent metal oxide to the trivalent metal oxide or the tetravalent metal oxide is (2-4):1, wherein when the divalent metal oxide, the trivalent metal oxide and the tetravalent metal oxide are composited, the molar ratio of the trivalent metal oxide to the tetravalent metal oxide is (5-20):1.

[0031] Furthermore, in step 1), the precursors of the divalent, trivalent and tetravalent metals are composed of one or more of nitrates, sulfates, chlorides and organic salts of the divalent or trivalent metals.

[0032] Furthermore, in step 1), the pH value of the divalent, trivalent and tetravalent metal precipitation is between 8.0 and 11.

[0033] Furthermore, in step 1), the metal salt precipitation time is 0.5-5h.

[0034] Furthermore, in step 1), the condition for the metal salt to form a precipitate is to control the pH of the precipitate by adding an inorganic base or an organic base such as sodium hydroxide, potassium hydroxide, lithium hydroxide, urea, hexamethylenetetramine, etc.

[0035] Furthermore, in step 1), the drying temperature of the formed metal precipitate is 60-120° C., and the drying time is 2-24 hours.

[0036] Furthermore, in step 1), the metal precipitate is calcined at a temperature of 300-800° C. for 0.01-5 h, and then cooled to room temperature.

[0037] Furthermore, in step 1), the atmosphere for calcining the metal precipitate is one of air, nitrogen and argon.

[0038] Furthermore, in step 2), the metal nanoparticles are composed of one or more of Ni, Co, and Cu.

[0039] Furthermore, in step 2), a certain amount of the above composite metal oxide is weighed and placed in a tubular furnace, and the temperature is raised to 300-800° C. in a hydrogen atmosphere and maintained for 0.01-5 h to obtain the metal nanoparticles supported by the composite oxide.

[0040] Furthermore, in step 2), the solid powder of the composite metal oxide is spread flat on the bottom of a porcelain boat, and then the porcelain boat is placed in the constant temperature zone in the center of the quartz tube of a tubular furnace, and the tubular furnace is gradually heated at a heating rate of 1-20°C / min. When the temperature of the constant temperature zone in the center of the quartz tube reaches 300-800°C, it is maintained for 0.01-5h, and then cooled to room temperature to obtain metal nanoparticles loaded with the composite oxide.

[0041] The beneficial effects of the present invention are:

[0042] 1. The catalyst of the present invention can realize, for the first time, the efficient synthesis of pyrrole compounds by dehydrogenation and cross-condensation of alcohol molecules and 2-amino alcohol molecules without the addition of an external base, and for the first time, the substrate alcohol is expanded from the existing reports that only aromatic primary alcohols or secondary alcohols participate in the reaction to aliphatic primary alcohols, providing a greener and more sustainable method for preparing pyrrole compounds.

[0043] 2. In the catalyst of the present invention, since the metal nanoparticles are loaded on the acid-base bifunctional composite oxide carrier to form a synergistic catalytic effect, in the reaction of catalyzing alcohol molecules and 2-amino alcohol molecules to prepare pyrroles, the metal cations on the acid-base bifunctional composite oxide carrier act as Lewis bases to promote the activation of the OH bond in the alcohol / 2-amino alcohol, so that it generates corresponding alkoxy species, and then the alkoxy species are adsorbed in the metal nanoparticles, and then Cα-H is activated to generate C=O bonds. The generated carbonyl compounds and amines undergo cross-condensation on the acid-base bifunctional composite oxide carrier, wherein the acid center on the composite oxide can activate the C=O bond, and the base center activates the NH bond, thereby promoting the condensation and dehydration of the two to generate imine compounds, and then continue to undergo intramolecular dehydration and cyclization on the composite oxide to generate pyrrole compounds.

[0044] 3. By using the catalyst of the present invention, the yield of pyrrole compounds is 30-99%. DETAILED DESCRIPTION

[0045] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solution of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0046] Example 1 Highly Selective Synthesis of Pyrrole from Ethanol and 2-Aminoethanol Catalyzed by Supported Ni Catalyst

[0047] Catalyst preparation: Weigh 0.02 mol, 0.009 mol and 0.001 mol of nickel nitrate, aluminum nitrate and zirconium nitrate respectively and fully dissolve them in 150 mL of deionized water, then weigh 0.06 mol of sodium hydroxide and fully dissolve them in 150 mL of deionized water. At the same time, weigh 0.005 mol of sodium carbonate and dissolve them in a four-necked flask containing 150 mL of deionized water. Drop the metal salt solution and sodium hydroxide solution into the four-necked flask at the same time. After the metal salt solution is added, transfer the four-necked flask to a constant temperature water bath at 60 ° C and continue to stir and crystallize for 24 hours. Filter under reduced pressure, wash with deionized water until neutral, wash once with anhydrous ethanol, filter, and dry in an oven. The precursor prepared above is reduced in hydrogen to prepare a supported Ni catalyst.

[0048] Catalytic reaction: Accurately weigh 3.0 mL of ethanol, 0.5 mmol of 2-aminoethanol and 30 mg of catalyst into a 20 mL glass reaction tube, then place the glass tube reactor in an oil bath at 120°C and continue the reaction for 24 hours. After the reaction, the reactor was quickly cooled to room temperature. The liquid product was analyzed by gas chromatography. The conversion rate of 2-aminoethanol was greater than 99%, and the yield of pyrrole was 93.3%.

[0049] Example 2 Highly Selective Synthesis of 3-Methylpyrrole by Using Supported Ni Catalyst to Catalyze Propanol and 2-Aminoethanol

[0050] Catalyst preparation: Weigh 0.02 mol, 0.009 mol and 0.001 mol of nickel nitrate, aluminum nitrate and zirconium nitrate respectively and fully dissolve them in 150 mL of deionized water, then weigh 0.06 mol of sodium hydroxide and fully dissolve it in 150 mL of deionized water. At the same time, weigh 0.005 mol of sodium carbonate and dissolve it in a four-necked flask containing 150 mL of deionized water. Drop the metal salt solution and sodium hydroxide solution into the four-necked flask at the same time. After the metal salt solution is added, transfer the four-necked flask to a constant temperature water bath at 60 ° C and continue to stir and crystallize for 24 hours. Filter under reduced pressure, wash with deionized water until neutral, wash once with anhydrous ethanol, filter, and dry in an oven. The precursor prepared above is reduced in hydrogen to prepare a supported Ni catalyst.

[0051] Catalytic reaction: Accurately weigh 3.0 mL of propanol, 0.5 mmol of 2-aminoethanol and 30 mg of catalyst into a 20 mL glass reaction tube, then place the glass tube reactor in an oil bath at 120°C and continue the reaction for 24 hours. After the reaction, the reactor was quickly cooled to room temperature. The liquid product was analyzed by gas chromatography. The conversion rate of 2-aminoethanol was greater than 99%, and the yield of 3-methylpyrrole was 89.2%.

[0052] Example 3 Highly Selective Synthesis of 3-Ethylpyrrole by Using Supported Ni Catalyst to Catalyze Butanol and 2-Aminoethanol

[0053] Catalyst preparation: Weigh 0.02 mol, 0.009 mol and 0.001 mol of nickel nitrate, aluminum nitrate and zirconium nitrate respectively and fully dissolve them in 150 mL of deionized water, then weigh 0.06 mol of sodium hydroxide and fully dissolve it in 150 mL of deionized water. At the same time, weigh 0.005 mol of sodium carbonate and dissolve it in a four-necked flask containing 150 mL of deionized water. Drop the metal salt solution and sodium hydroxide solution into the four-necked flask at the same time. After the metal salt solution is added, transfer the four-necked flask to a constant temperature water bath at 60 ° C and continue to stir and crystallize for 24 hours. Filter under reduced pressure, wash with deionized water until neutral, wash once with anhydrous ethanol, filter, and dry in an oven. The precursor prepared above is reduced in hydrogen to prepare a supported Ni catalyst.

[0054] Catalytic reaction: Accurately weigh 3.0 mL of butanol, 0.5 mmol of 2-aminoethanol and 30 mg of catalyst into a 20 mL glass reaction tube, then place the glass tube reactor in an oil bath at 120°C and continue the reaction for 24 hours. After the reaction, the reactor was quickly cooled to room temperature. The liquid product was analyzed by gas chromatography. The conversion rate of 2-aminoethanol was greater than 99%, and the yield of 3-ethylpyrrole was 98.9%.

[0055] Example 4 Highly Selective Synthesis of 2-Methylpyrrole by Isopropanol and 2-aminoethanol Catalyzed by Supported Ni Catalyst

[0056] Catalyst preparation: Weigh 0.02 mol, 0.009 mol and 0.001 mol of nickel nitrate, aluminum nitrate and zirconium nitrate respectively and fully dissolve them in 150 mL of deionized water, then weigh 0.06 mol of sodium hydroxide and fully dissolve it in 150 mL of deionized water. At the same time, weigh 0.005 mol of sodium carbonate and dissolve it in a four-necked flask containing 150 mL of deionized water. Drop the metal salt solution and sodium hydroxide solution into the four-necked flask at the same time. After the metal salt solution is added, transfer the four-necked flask to a constant temperature water bath at 60 ° C and continue to stir and crystallize for 24 hours. Filter under reduced pressure, wash with deionized water until neutral, wash once with anhydrous ethanol, filter, and dry in an oven. The precursor prepared above is reduced in hydrogen to prepare a supported Ni catalyst.

[0057] Catalytic reaction: Accurately weigh 3.0 mL of isopropanol, 0.5 mmol of 2-aminoethanol and 30 mg of catalyst into a 20 mL glass reaction tube, then place the glass tube reactor in an oil bath at 120°C and continue the reaction for 24 hours. After the reaction, the reactor was quickly cooled to room temperature. The liquid product was analyzed by gas chromatography. The yield of 2-methylpyrrole was 99%.

[0058] Example 5 Highly Selective Synthesis of Pyrrole from Ethanol and 2-Aminoethanol Catalyzed by Supported Co Catalyst

[0059] Catalyst preparation: Weigh 0.02 mol and 0.01 mol of cobalt nitrate and aluminum nitrate respectively and fully dissolve them in 150 mL of deionized water, then weigh 0.06 mol of sodium hydroxide and fully dissolve it in 150 mL of deionized water. At the same time, weigh 0.005 mol of sodium carbonate and dissolve it in a four-necked flask filled with 150 mL of deionized water. Drop the metal salt solution and sodium hydroxide solution into the four-necked flask at the same time. After the metal salt solution is added, transfer the four-necked flask to a constant temperature water bath at 60 ° C and continue to stir and crystallize for 24 hours. Filter under reduced pressure, wash with deionized water until neutral, then wash once with anhydrous ethanol, filter, and dry in an oven. The precursor prepared above is reduced in hydrogen to prepare a supported Co catalyst.

[0060] Catalytic reaction: Accurately weigh 3.0 mL of ethanol, 0.5 mmol of 2-aminoethanol and 30 mg of catalyst into a 20 mL glass reaction tube, then place the glass tube reactor in an oil bath at 120°C and continue the reaction for 24 hours. After the reaction, the reactor was quickly cooled to room temperature. The liquid product was analyzed by gas chromatography. The conversion rate of 2-aminoethanol was greater than 99%, and the yield of pyrrole was 44.2%.

[0061] Example 6 Highly Selective Synthesis of Pyrrole by Using Supported Cu Catalyst to Catalyze Ethanol and 2-Aminoethanol

[0062] Catalyst preparation: Weigh 0.005 mol, 0.02 mol and 0.01 mol of copper nitrate, zinc nitrate and aluminum nitrate respectively and fully dissolve them in 150 mL of deionized water, then weigh 0.06 mol of sodium hydroxide and fully dissolve it in 150 mL of deionized water. At the same time, weigh 0.005 mol of sodium carbonate and dissolve it in a four-necked flask filled with 150 mL of deionized water. Drop the metal salt solution and sodium hydroxide solution into the four-necked flask at the same time. After the metal salt solution is added, transfer the four-necked flask to a constant temperature water bath at 60 ° C and continue to stir and crystallize for 24 hours. Filter under reduced pressure, wash with deionized water until neutral, wash once with anhydrous ethanol, filter, and dry in an oven. The precursor prepared above is reduced in hydrogen to prepare a supported Cu catalyst.

[0063] Catalytic reaction: Accurately weigh 3.0 mL of ethanol, 0.5 mmol of 2-aminoethanol and 30 mg of catalyst into a 20 mL glass reaction tube, then place the glass tube reactor in an oil bath at 120°C and continue the reaction for 24 hours. After the reaction, the reactor was quickly cooled to room temperature. The liquid product was analyzed by gas chromatography. The conversion rate of 2-aminoethanol was greater than 99%, and the yield of pyrrole was 30%.

[0064] The above description is only a preferred embodiment of the present invention and does not constitute any other form of limitation to the present invention. Any modification or equivalent change made based on the technical essence of the present invention still falls within the scope of protection required by the present invention.

Claims

1. A method for the sustainable preparation of pyrrole compounds, characterized in that: The raw materials are composed of abundant and readily available alcohol molecules and 2-amino alcohol molecules. ； Wherein, the R1 and R2 groups in the alcohol molecule are respectively composed of one or more of H, methyl, ethyl, propyl, phenyl, and furanyl groups; The R3 and R4 groups of the 2-amino alcohol molecule are respectively composed of one or more of H, methyl, ethyl, propyl, phenyl, and furanyl groups; The alcohol molecules are both reactants and reaction solvents, the molar ratio of the alcohol molecules to the 2-amino alcohol molecules is (2-100):1, the amount of the catalyst added is 1-90% of the molar number of the 2-amino alcohol molecules added, the reaction temperature is 50-250°C, and the reaction time is 0.5-30 h; The catalyst is composed of composite oxide-supported metal nanoparticles; the composite oxide is composed of divalent metal oxides and trivalent and / or tetravalent metal oxides; the divalent metal oxide is selected from nickel oxide, cobalt oxide, magnesium oxide, zinc oxide, the trivalent metal oxide is selected from aluminum oxide, and the tetravalent metal oxide is selected from zirconium oxide; the metal nanoparticles are composed of one or more of Ni, Co, and Cu.

2. The method for preparing pyrrole compounds according to claim 1, characterized in that: The reactor is one of a glass tube reactor, a stainless steel reactor with a polytetrafluoroethylene lining and a fixed bed reactor.

3. The method for preparing pyrrole compounds according to claim 1, characterized in that: The reaction atmosphere is one of air, nitrogen and argon, and the pressure is 0.1-2.0 MPa.

4. The method for preparing pyrrole compounds according to claim 1, characterized in that: The molar ratio of the divalent metal oxide to the trivalent or tetravalent metal oxide is (2-4):1; wherein when the divalent metal oxide, the trivalent metal oxide and the tetravalent metal oxide are compounded, the molar ratio of the trivalent metal oxide to the tetravalent metal oxide is (5-20):1.

Images