An iron complex based on bisisoquinoline and a preparation method and application thereof

Abstract

The application provides a bisisoquinoline-based iron complex with the structure shown in formula (I), and also provides a preparation method of the bisisoquinoline-based iron complex and application of the bisisoquinoline-based iron complex as a catalyst for hydroxylation reaction of anisole, and further provides a method for preparing p-hydroxyanisole and co-producing o-hydroxyanisole. When the bisisoquinoline-based iron complex provided by the application is used for catalyzing the hydroxylation reaction of anisole, excellent reaction activity and p-hydroxy product selectivity can be achieved, a new process idea is provided for industrialized production of p-hydroxyanisole, and the bisisoquinoline-based iron complex has very important economic value and social value.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of catalyst preparation, in particular to a bishydroquinoline-based iron complex, a preparation method thereof and application of the iron complex in catalyzing hydroxylation of anisole, and a method for preparing p-hydroxyanisole and co-producing o-hydroxyanisole. BACKGROUND

[0002] P-hydroxyanisole is also known as p-methoxyphenol, English name is 4-methoxyphenol, and is abbreviated as MEHQ. MEHQ is an important organic chemical intermediate, which plays an important role in the pharmaceutical, pesticide, perfume and other industries, and can be used for synthesizing stabilizers of some plastic monomers, ultraviolet absorbers, food preservatives and the like. The main role of MEHQ is to act as a polymerization inhibitor and anti-aging agent in polymer production, especially in the process of generating acrylonitrile, acrylic acid and related products, and its unique advantage lies in that it can directly participate in the polymerization of the final product without the need for prior removal.

[0003] Currently, there are mainly two processes for industrial preparation of p-hydroxyanisole, which can be divided into p-aminophenyl anisole diazotization method and p-phenylenediamine etherification method according to raw materials. The p-aminophenyl anisole diazotization method is to use methoxyaniline as raw material, and p-hydroxyanisole is prepared after diazotization and hydrolysis. The reaction needs to be carried out under high temperature and concentrated acid conditions, the process is relatively complicated, the equipment requirements are high, and a large amount of nitrogen-containing wastewater is generated; the p-phenylenediamine etherification method is mainly divided into dimethyl sulfate method and methanol method, although both start from p-phenylenediamine, but dimethyl sulfate is a highly toxic chemical, which has high requirements for operation equipment and personnel, and a large amount of alkali is needed to neutralize the by-products, which increases the environmental pressure and processing cost. Even the relatively mild methanol method also faces the problems of purity control and by-product management. Therefore, the above two synthesis processes have certain limitations.

[0004] In recent years, a new synthesis process using anisole and hydrogen peroxide as raw materials has gradually attracted attention. This process has the advantages of mild reaction conditions, high yield and high-value by-product guaiacol (o-hydroxyanisole), and most importantly, the reaction product is water, which is a green synthesis process.

[0005] In order to solve the problems of low reaction conversion rate and yield in the existing anisole hydroxylation process, Chinese patent application CN 113731400A discloses a method for synthesizing p-hydroxyanisole and guaiacol from anisole and hydrogen peroxide, which uses K7[MnV 13 O 38]·18H2O as a catalyst has high catalytic activity, can significantly improve the conversion rate of anisole and the yield of the target product (p-hydroxyanisole) in the hydroxylation reaction, thereby effectively promoting the clean production of p-hydroxyanisole, and ultimately realizing the yield of the hydroxylation product of 76% and the selectivity of 98%. Chinese Patent CN115490579B discloses a preparation method of o / p-hydroxyanisole, mainly including catalyst optimization and reaction process optimization. The catalyst optimization is: first, prepare the alkali-modified microspherical titanium silicalite molecular sieve, and then prepare the microspherical titanium silicalite molecular sieve catalyst loaded with copper and cadmium by the equal-volume impregnation method. The reaction process optimization is: the reaction temperature is room temperature to 150°C, and the reaction pressure is 0.1 to 5.0 MPa. The hydroxyanisole obtained by the preparation method has excellent yield and selectivity, the conversion rate is about 22%, the selectivity is about 97%, and the service life of the catalyst reaches more than 2,000 hours. However, the above two catalysts are both heterogeneous catalysts, which are not fully contacted with the reaction liquid, and still have the disadvantages of low catalytic activity. SUMMARY

[0006] To make up for the deficiencies in the prior art, one object of the present application is to provide an iron complex based on bisisoquinoline, which has excellent catalytic activity when used to catalyze the hydroxylation reaction of anisole, high substrate conversion rate, and good selectivity of p-hydroxyanisole product, and thus has great application potential.

[0007] Another object of the present application is to provide a preparation method and application of the iron complex based on bisisoquinoline.

[0008] Still another object of the present application is to provide a method for preparing p-hydroxyanisole and co-producing o-hydroxyanisole.

[0009] The first aspect of the present application provides an iron complex based on bisisoquinoline, which has the structure shown in formula (I):

[0010]

[0011] wherein R is the same or different, each independently represents hydrogen, C1-C6 alkyl, C1-C6 alkoxy or C3-C8 cycloalkyl.

[0012] In some preferred embodiments, R can each independently represent hydrogen, C1-C4 alkyl or C1-C4 alkoxy. In some more preferred embodiments, R can each independently represent hydrogen, methyl, ethyl, n-propyl or isopropyl. In some most preferred embodiments, the iron complex based on bisisoquinoline can be the following compound:

[0013]

[0014] The second aspect of the present application provides a preparation method of the iron complex based on bis-isoquinoline according to any one of the above technical solutions, and the preparation method comprises the following steps:

[0015] S1: reacting an isoquinoline derivative represented by a structure of formula (I-1) with an alkyltin chloride reagent to obtain a first intermediate represented by a structure of formula (I-2);

[0016]

[0017] S2: reacting the first intermediate with a halogenated isoquinoline represented by a structure of formula (I-3) (i.e. Stile coupling reaction) to obtain a second intermediate represented by a structure of formula (I-4);

[0018]

[0019] S3: reacting the second intermediate with an iron source containing Fe 2+ to obtain the iron complex based on bis-isoquinoline (i.e. complexation reaction);

[0020]

[0021] wherein R1 represents C1-C6 alkyl, for example, can represent methyl, ethyl, n-propyl, isopropyl or tert-butyl;

[0022] X represents a halogen atom, for example, can represent Br;

[0023] R are the same or different, each independently defined as in any one of the above technical solutions.

[0024] In the preparation method provided by the present application, the iron source can be one or more of ferrous sulfate, ferrous nitrate, ferrous chloride and ferrous hydroxide.

[0025] In the preparation method provided by the present application, the mass ratio of the second intermediate to the iron source can be 1:1-6, for example, can be 1:2-4.

[0026] In the preparation method provided by the present application, in the step S1, the isoquinoline derivative and the alkyltin chloride reagent can be reacted in the presence of a butyl lithium catalyst (for example, n-butyl lithium) in a first organic solvent. In some preferred embodiments, the reaction temperature in the step S1 can be 20-100°C, for example, can be 30-60°C.

[0027] In the preparation method, in step S1, the alkyl tin chloride reagent can be trimethyl tin chloride. In some preferred embodiments, the mass ratio of the isoquinoline derivative to trimethyl tin chloride can be 1:0.4-2, for example, 1:0.6-1.5, and further 1:0.6-1.2.

[0028] In the preparation method, in step S1, the mass ratio of the isoquinoline derivative to the butyl lithium catalyst can be 1:0.05-0.8, for example, 1:0.1-0.4, and further 1:0.2-0.3.

[0029] In the preparation method, in step S1, the first organic solvent can be one or more of toluene, ethylbenzene, tetrahydrofuran, N,N-dimethylformamide (DMF), diethyl ether. In some preferred embodiments, the mass ratio of the isoquinoline derivative to the first organic solvent can be 1:2-10, for example, 1:3-8.

[0030] In the preparation method, the reaction environment in step S1 is anhydrous and oxygen-free environment, which can be achieved by common operations or means in the art.

[0031] In the preparation method, in step S1, the addition (for example, dropwise addition) of the butyl lithium catalyst needs to be maintained in a low-temperature environment of-100 to-50℃, and then slowly increased to the required reaction temperature after the addition of the butyl lithium catalyst is completed. The low-temperature environment can be achieved by common operations or means in the art.

[0032] In the preparation method, the reaction time in step S1 can be monitored and controlled in real time according to the reaction scale, actual reaction conditions, etc., for example, 2-30h, and further 5-20h.

[0033] In the preparation method, in step S1, distilled water or deionized water can be added to quench the reaction after the reaction is completed, and the obtained residue after removal of the first organic solvent can be purified by a silica gel chromatographic column, wherein the elution system can include n-hexane, ethyl acetate, dichloromethane, etc. or a mixture thereof.

[0034] In the preparation method, in step S2, the first intermediate and the halogenated isoquinoline can be reacted in a second organic solvent. In some preferred embodiments, the reaction temperature in step S2 can be 60-200℃, for example, 60-120℃.

[0035] In the preparation method, the halogenated isoquinoline in step S2 can be 2-bromoisoquinoline. In some preferred embodiments, the mass ratio of the first intermediate to 2-bromoisoquinoline can be 1:1-3, for example, 1:1-1.5.

[0036] In the preparation method, the second organic solvent in step S2 can be one or more of toluene, chloroform, dichloromethane, and tetrahydrofuran. In some preferred embodiments, the mass ratio of the first intermediate to the second organic solvent can be 1:2-10, for example, 1:4-6.

[0037] In the preparation method, the reaction environment in step S2 is anhydrous and oxygen-free environment, which can be achieved by common operations or means in the art.

[0038] In the preparation method, the reaction time in step S2 can be monitored and controlled in real time according to the reaction scale, actual reaction conditions, and the like, for example, 2-30 h, and further, 5-20 h.

[0039] In the preparation method, after the reaction in step S2, the second organic solvent can be removed, and the obtained residue can be separated and purified by a silica gel chromatographic column, wherein the elution system can include dichloromethane, ethyl acetate, petroleum ether, n-hexane, and the like, or a mixture thereof.

[0040] In the preparation method, in step S3, the second intermediate and the iron source containing Fe 2+ can be reacted in a third organic solvent. In some preferred embodiments, the reaction temperature in step S3 can be 10-80°C, for example, 20-40°C, and further, room temperature.

[0041] In the preparation method, in step S3, the third organic solvent can be one or more of N,N-dimethylformamide, dimethyl sulfoxide (DMSO), methanol, and acetonitrile. In some preferred embodiments, the mass ratio of the second intermediate to the third organic solvent can be 1:1-10, for example, 1:2-4.

[0042] In the preparation method, the reaction time in step S3 can be monitored and controlled in real time according to the reaction scale, actual reaction conditions, and the like, for example, 0.5-10 h, and further, 0.5-5 h.

[0043] In the preparation method, in step S3, after the reaction, the precipitated solid can be separated, washed, and dried to obtain the iron complex.

[0044] In the preparation method provided by the present application, the desired material can be obtained through a separation step. The separation equipment or method can be common in the art, including but not limited to natural sedimentation, (normal pressure or vacuum) filtration, centrifugation and the like, and common equipment thereof.

[0045] In the preparation method provided by the present application, the solvent can be removed by common equipment or method in the art, for example, a rotary evaporator can be used to remove the solvent by evaporation under reduced pressure.

[0046] In the preparation method provided by the present application, the washing step refers to washing the material with distilled water or deionized water until the surface of the material is close to or presents neutral. The number of washing times can be adjusted according to the actual situation, for example, it can be 2-5 times, and usually it can be 3 times.

[0047] In the preparation method provided by the present application, the drying step refers to removing the residual solvent or moisture on the surface of the material by heating or the like. The drying time and temperature can be adjusted according to the actual situation, as long as it does not affect the properties of the material itself.

[0048] In the preparation method provided by the present application, room temperature refers to 25±5℃.

[0049] The third aspect of the present application provides the use of the iron complex based on bis-isoquinoline as a catalyst for the hydroxylation reaction of anisole.

[0050] In some preferred embodiments, the hydroxylation reaction of anisole can be a reaction of anisole with an oxidant to prepare p-hydroxyanisole and co-produce o-hydroxyanisole. In some more preferred embodiments, the oxidant can be hydrogen peroxide with a mass concentration of 20-60%.

[0051] The fourth aspect of the present application provides a method for preparing p-hydroxyanisole and co-producing o-hydroxyanisole, which comprises: performing a hydroxylation reaction of anisole with an oxidant in the presence of a catalyst to prepare p-hydroxyanisole and co-produce o-hydroxyanisole, wherein the catalyst is the iron complex based on bis-isoquinoline according to any one of the above technical solutions.

[0052] In some preferred embodiments, the amount of the catalyst can be 0.1-1.5% of anisole by mass percentage, for example, it can be 0.2-0.8%, and further it can be 0.3-0.5%.

[0053] In some preferred embodiments, the oxidant can be hydrogen peroxide with a mass concentration of 20-60%, for example, it can be hydrogen peroxide with a mass concentration of 30-50%.

[0054] In some preferred embodiments, the hydroxylation reaction can be carried out in a reaction solvent, for example, the reaction solvent is one or more of acetone, methanol, water, ethanol, and the mass ratio of the anisole to the reaction solvent can be 1:0.5-5, for example, can be 1:0.5-1.5.

[0055] In some preferred embodiments, the reaction temperature of the hydroxylation reaction can be 50-80°C, and the reaction pressure can be normal pressure.

[0056] In some preferred embodiments, the reaction time of the hydroxylation reaction can be 2-20h, for example, can be 5-10h.

[0057] The technical solution provided by the present application has the following advantages:

[0058] (1) The iron complex based on bisisoquinoline provided by the present application can be converted into active Fe 2+ The bulky and conjugated ligand structure is introduced, which can effectively pair with anisole during the anisole hydroxylation reaction, thereby significantly improving the reaction activity; the bulky bisisoquinoline ligand structure can also form steric hindrance to the ortho-position side reaction of the methoxy group, thereby reducing the occurrence of the ortho-position reaction, and can significantly improve the selectivity of p-anisole, and the product has higher added value.

[0059] (2) The iron complex provided by the present application can be dissolved in common reaction solvents, so that the catalysis of the iron complex on the anisole hydroxylation reaction can be a homogeneous reaction. Compared with traditional heterogeneous catalysts, the catalyst has more sufficient contact with the reaction materials, and thus has higher catalytic activity, thereby greatly improving the reaction rate.

[0060] (3) The preparation method of the iron complex provided by the present application is simple, easy to operate and control, does not require high cost, has strong industrial practicability, provides a new process idea for the industrial production of p-anisole, and thus has very important economic value and social value. DETAILED DESCRIPTION

[0061] The specific embodiments of the catalyst of the present application will be described below. It should be first clarified that the catalyst disclosed in the present application has different forms, and should not be understood or interpreted as being limited to the specific embodiments described in the present application. At the same time, the purpose of providing the embodiments is to make the disclosure of the present application more complete and complete, and to fully convey the intention and scope of the subject to those skilled in the art. Therefore, any other embodiments that do not have the premise of creativity should belong to the protection scope of the present application.

[0062] Unless otherwise defined, the terms used in the present application should be considered to be in accordance with the general meaning that can be understood by those skilled in the art, and some common terms are introduced and explained as follows:

[0063] As used herein, the singular forms "a", "an" and "the" include singular and plural referents unless the content clearly dictates otherwise.

[0064] As used herein, "comprising" or "including" or "having" has an open, non-limiting meaning and is used in its conventional sense, such that it implies the inclusion of any stated integer or step or group of integers or steps, but not the exclusion of any other integer or step or group of integers or steps.

[0065] As used herein, "one implementation" or "an implementation" refers to a particular noted characteristic, structure, or property of a subject being described when the phrase appears. Thus, "one implementation" appearing in various places in this document are not all referring to the same implementation. On the other hand, in some implementations, certain features of one implementation can be included in other implementations without the other features of the other implementation. Combinations of implementations with different features are also expressly contemplated herein, even if such combinations are not explicitly listed.

[0066] As used herein, "C1-Cn" includes C1-C2, C1-C3,... C1-Cn. For example, a "C1-C6" group means that the moiety has from 1 to 6 carbon atoms, i.e. the group includes 1 carbon atom, 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, 5 carbon atoms or 6 carbon atoms. Thus, for example, "C1-C4 alkyl" means an alkyl group having from 1 to 4 carbon atoms, i.e. the alkyl group is selected from methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, t-butyl, and the like. Numerical ranges as used herein, such as "1 to 6", are used to describe various embodiments. Thus, for example, the range of 1 to 6 includes individual integers such as 1, 2, 3, 4, 5, and 6.

[0067] The term "alkyl" as used herein alone or in combination refers to a straight or branched hydrocarbon group of from 1 to 6 carbon atoms. n H 2n+1 A hydrocarbon group of the general formula: -CnH2n+1, where n is an integer greater than or equal to 1. The alkyl group can be linear or branched. The alkyl groups of the present application contain from 1 to 6 carbon atoms, non-limiting examples of alkyl groups include methyl, ethyl, n-propyl, i-propyl, 2-methyl-l-propyl, 2-methyl-2-propyl, 2-methyl-l-butyl, 3-methyl-l-butyl, 2-methyl-3-butyl, 2,2-dimethyl-l-propyl, 2-methyl-1-pentyl, 3-methyl-l-pentyl, 4-methyl-l-pentyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl, 2,2-dimethyl-l-butyl, 3,3-dimethyl-l-butyl, 2-ethyl-l-butyl, n-butyl, i-butyl, s-butyl, t-butyl, n-pentyl, i-pentyl, neopentyl, t-pentyl, hexyl, and the like, as well as the individual isomers thereof.

[0068] The term "alkyl" used herein alone or in combination refers to an alkyl group attached to other groups, for example, the alkyl group in alkoxy, and has the same definition as when used alone.

[0069] The term "alkoxy" used herein alone or in combination refers to an alkyl ether group, represented as "alkyl-O-". Non-limiting examples of alkoxy groups include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, t-butoxy, and the like.

[0070] The term "cycloalkyl" used herein alone or in combination refers to a non-aromatic saturated carbocyclic ring, which can include a monocyclic ring (having one ring), a bicyclic ring (having two rings), or a polycyclic ring (having more than two rings), and the rings can be fused or spiro. The cycloalkyl group can have 3 to 8 ring-forming carbon atoms, for example, 3 to 6 ring-forming carbon atoms. Non-limiting examples of cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and the like.

[0071] The term "halogen atom" used herein alone or in combination refers to fluorine (F), chlorine (Cl), bromine (Br), or iodine (I).

[0072] The technical solutions of the present application are further described in detail below in combination with specific examples.

[0073] In the embodiments of the present application, an Agilent liquid chromatograph is used to calibrate the content of anisole, o-anisole, and p-anisole in the system by an external standard method, and a potentiometric titrator is used to determine hydrogen peroxide.

[0074] The silica gel chromatographic column used in the embodiments of the present application is filled with 30-mesh silica gel, and the raw materials or reagents used are commercially available products unless otherwise specified.

[0075] The percentages used in the embodiments of the present application are mass percentages unless otherwise specified.

[0076] Example 1

[0077] 1. Preparation of catalyst Cat-1

[0078] Into a dry and oxygen-free sealed three-necked flask, 40 g of isoquinoline and 250 g of tetrahydrofuran were injected, and 80 g of n-butyllithium solution (1.6 mol / L) was slowly added dropwise into the reaction system at -78℃. After the dropwise addition was completed, the reaction was continued at room temperature for 3 h, and then 50 g of trimethyltin chloride solution (the mass concentration of trimethyltin chloride was 65%) was quickly added into the reaction system. The temperature was raised to 60℃ and the reaction was continued for 6 h. The reaction was quenched by adding water, and the solvent was removed by rotary evaporation. The obtained residue was purified by a silica gel chromatographic column, and the eluent was a mixed solution of ethyl acetate and n-hexane (mass ratio 1:4) to obtain compound 1-1.

[0079] Take 40 g of compound 1-1 dissolved in 180 g of toluene, add 60 g of 2-bromoisoquinoline, heat to 110°C and reflux for 12 h. After the reaction is completed, the reaction liquid is rotary evaporated to remove the solvent. The obtained residue is purified by silica gel chromatography column with dichloromethane as the eluent to obtain compound 1-2.

[0080] Take 20 g of compound 1-2 and 40 g of ferrous sulfate solid, dissolve in 80 g of DMF, stir at room temperature for 3 h, precipitate the flocculent solid, filter, wash and dry to obtain the iron ion ligand catalyst Cat-1.

[0081] Elemental analysis: C 76.04%, H 4.26%, Fe 9.82%, N 9.86% (actual value).

[0082] Nuclear magnetic hydrogen spectrum analysis: 1 H NMR (400 MHz, CDCl3) δ 7.16 (2H), 7.42 (4H), 7.49 (4H), 7.63 (4H), 7.92 (4H), 8.21 (2H), 8.54 (2H), 8.91 (2H).

[0083] 2. Catalyst performance evaluation

[0084] Take 0.2 g of Cat-1 and 100 g of reaction raw material (anisole: 27.5% hydrogen peroxide: acetone = 1:0.3:0.8, mass ratio) mixture, stop the reaction after 6 h at 60°C, take the reaction liquid for liquid chromatography analysis and titration analysis, the conversion rate of hydrogen peroxide is greater than 99%, the total selectivity of hydroxyanisole is greater than 95%, and the molar ratio of p-hydroxyanisole / ortho-hydroxyanisole is 3.65.

[0085] Example 2

[0086] 1. Preparation of catalyst Cat-2

[0087] Into anhydrous and oxygen-free sealed three-necked flask, inject 40 g of 6-methylisoquinoline and 320 g of toluene, slowly add 120 g of 1.6 mol / L n-butyllithium solution to the reaction system at -98°C, then continue to react for 2 h after the addition is completed, then quickly add 60 g of trimethyltin chloride solution (trimethyltin chloride mass concentration is 70%) to the reaction system, and react for 10 h at 50°C. Quench the reaction by adding water, rotary evaporate to remove the solvent, and purify the obtained residue by silica gel chromatography column with ethyl acetate and n-hexane mixture solution (mass ratio is 1:4) as the eluent to obtain compound 2-1.

[0088] Take 40 g of compound 2-1 dissolved in 240 g of dichloromethane, add 60 g of 2-bromoisoquinoline, heat to 120°C and reflux for 16 h. After the reaction is completed, the reaction liquid is rotary evaporated to remove the solvent, and the obtained residue is purified by silica gel chromatography column, eluent is dichloromethane, to obtain compound 2-2.

[0089] Take 20 g of compound 2-2 and 60 g of ferrous nitrate solid, dissolve in 40 g of methanol, stir at room temperature for 3 h, precipitate the flocculent solid, filter, wash and dry to obtain the iron ion ligand catalyst Cat-2.

[0090] Elemental analysis: C 76.51%, H 4.73%, Fe 9.36%, N 9.39% (actual value).

[0091] Nuclear magnetic hydrogen spectrum analysis: 1 H NMR (400 MHz, CDCl3) δ 2.34 (6H), 7.16 (2H), 7.28 (2H), 7.42 (4H), 7.49 (4H), 7.63 (4H), 7.86 (2H), 7.92 (4H), 8.21 (2H), 8.51 (2H), 8.92 (2H).

[0092] 2. Catalyst performance evaluation

[0093] Take 0.2 g of Cat-2 and 100 g of reaction raw material (anisole: 27.5% hydrogen peroxide: methanol = 1:0.4:1.2, mass ratio), stop the reaction after 5 h at 80°C, take the reaction liquid for liquid chromatography analysis and titration analysis, the conversion rate of hydrogen peroxide is greater than 99%, the total selectivity of hydroxyanisole is greater than 96%, and the molar ratio of p-hydroxyanisole / ortho-hydroxyanisole is 4.03.

[0094] Example 3

[0095] 1. Preparation of catalyst Cat-3

[0096] Into anhydrous and oxygen-free sealed three-necked flask, inject 40 g of 6-n-propylisoquinoline and 150 g of ethyl ether, slowly drop 80 g of 1.6 mol / L n-butyllithium solution into the reaction system at -50°C, after the drop is completed, continue to react for 2 h at room temperature, then quickly add 40 g of trimethyltin chloride solution (the mass concentration of trimethyltin chloride is 60%) into the reaction system, heat to 30°C and react for 18 h, quench the reaction with water, rotary evaporate to remove the solvent, and the obtained residue is purified by silica gel chromatography column, eluent is a mixed solution of ethyl acetate and n-hexane (mass ratio is 1:4), to obtain compound 3-1.

[0097] Take 40 g of compound 3-1 dissolved in 160 g of tetrahydrofuran, add 40 g of 2-bromoisoquinoline, heat to 70°C and reflux for 6 h. After the reaction is completed, the reaction liquid is rotary evaporated to remove the solvent, and the obtained residue is purified by silica gel chromatography column with dichloromethane as the eluent to obtain compound 3-2.

[0098] Take 20 g of compound 3-2 and 40 g of ferrous chloride solid, mix and dissolve in 40 g of DMSO, stir at room temperature for 0.5 h, precipitate flocculent solid, filter and wash to obtain iron ion ligand catalyst Cat-3.

[0099] Elemental analysis: C 77.30%, H 5.56%, Fe 8.56%, N 8.59% (actual value).

[0100] Nuclear magnetic hydrogen spectrum analysis: 1 H NMR (400 MHz, CDCl3) δ 0.90 (6H), 1.65 (4H), 2.62 (4H), 7.16 (2H), 7.28 (2H), 7.42 (4H), 7.49 (4H), 7.63 (4H), 7.86 (2H), 7.92 (4H), 8.21 (2H), 8.51 (2H), 8.92 (2H).

[0101] 2. Catalyst performance evaluation

[0102] Take 0.2 g of Cat-3 and 100 g of reaction raw material (anisole: 50% hydrogen peroxide: acetone = 1:0.2:0.5, mass ratio) and mix, stop the reaction after 10 h of reaction at 50°C, take the reaction liquid for liquid chromatography analysis and titration analysis, the conversion rate of hydrogen peroxide is greater than 99%, the total selectivity of hydroxyanisole is greater than 95.8%, and the molar ratio of p-hydroxyanisole / ortho-hydroxyanisole is 3.44.

[0103] Comparative example

[0104] Take 0.2 g of ferrocene and 100 g of reaction raw material (anisole: 50% hydrogen peroxide: acetone = 1:0.2:0.5, mass ratio) and mix, stop the reaction after 10 h of reaction at 50°C, take the reaction liquid for liquid chromatography analysis and titration analysis, the conversion rate of hydrogen peroxide is about 95%, the total selectivity of hydroxyanisole is about 85.3%, and the molar ratio of p-hydroxyanisole / ortho-hydroxyanisole is 2.58.

[0105] As can be seen from the comparative example, compared with ferrocene, the iron complex of the present application has more excellent catalytic performance due to the large volume of the bisisoquinoline ligand structure, the product yield is higher, and the selectivity of the p-hydroxyanisole product is obviously improved.

[0106] Unless otherwise defined, all terms used in disclosing the application, which are known to one of ordinary skill in the art (SOT) are to be interpreted as compatibly as possible in light of the special context in which each term is used. Conventionally, terms, especially those ending in "a" or "an" are intended to include both the singular and the plural, and terms, especially those ending in "one" or "said" are intended to include the singular or the plural.

[0107] The embodiments described herein are merely exemplary and are not intended to limit the scope of the application. Various other substitutions, changes and modifications can be suggested by those skilled in the art and it is intended that the application embrace all such changes and modifications within its scope, which is defined only by the claims.

Claims

1. An iron complex based on a bisisoquinoline, characterized in that, The iron complex has the structure shown in formula (Ⅰ): Wherein, R may be the same or different, and each independently represents hydrogen, C1-C6 alkyl, C1-C6 alkoxy or C3-C8 cycloalkyl.

2. The iron complex according to claim 1, characterized in that, The R values ​​may be the same or different, and each independently represents hydrogen, C1-C4 alkyl, or C1-C4 alkoxy.

3. The iron complex according to claim 2, characterized in that, The Rs may be the same or different, and each independently represents hydrogen, methyl, ethyl, n-propyl or isopropyl.

4. The iron complex according to claim 3, characterized in that, The iron complex is the following compound:

5. Process for the preparation of iron complexes based on bisisoquinoline according to any one of claims 1 to 4, characterized in that, Includes the following steps: S1: The isoquinoline derivative with the structure shown in formula (I-1) reacts with an alkyl tin chloride reagent to obtain the first intermediate with the structure shown in formula (I-2); S2: The first intermediate reacts with the haloisoquinoline of the structure shown in formula (I-3) to obtain the second intermediate of the structure shown in formula (I-4); S3: the second intermediate is reacted with a source of Fe 2+ to obtain the iron complex based on bisisoquinoline. Wherein, R1 represents a C1 to C6 alkyl group; X represents a halogen atom; R may be the same or different, each independently as defined in any one of claims 1-4.

6. The production method according to claim 5, wherein R1 represents methyl, ethyl, n-propyl, isopropyl, or tert-butyl; X represents Br.

7. The production method according to claim 5 or 6, characterized by, The iron source is one or more of ferrous sulfate, ferrous nitrate, ferrous chloride, and ferrous hydroxide.

8. The preparation method according to claim 7, characterized in that, The mass ratio of the second intermediate to the iron source is 1:1 to 6.

9. The production method according to claim 8, characterized by, The mass ratio of the second intermediate to the iron source is 1:2 to 4.

10. The production method according to claim 5 or 6, characterized by, In step S1, the isoquinoline derivative and the alkyltin chloride reagent are reacted in a first organic solvent in the presence of a butyllithium catalyst.

11. The method of claim 10, wherein, In step S1, the reaction temperature is 20–100°C.

12. The method of claim 11, wherein, The reaction temperature is 30℃~60℃.

13. The preparation method according to claim 10, characterized in that, The alkyl tin chloride reagent is trimethyltin chloride.

14. The method of claim 13, wherein, The mass ratio of the isoquinoline derivative to trimethyltin chloride is 1:0.4-2.

15. The method of claim 14, wherein, The mass ratio of the isoquinoline derivative to trimethyltin chloride is 1:0.6 to 1.

5.

16. The method of claim 10, wherein, The mass ratio of the isoquinoline derivative to the butyllithium catalyst is 1:0.05 to 0.

8.

17. The preparation method according to claim 16, characterized in that, The mass ratio of the isoquinoline derivative to the butyllithium catalyst is 1:0.1 to 0.

4.

18. The method of claim 10, wherein, The first organic solvent is one or more of toluene, ethylbenzene, tetrahydrofuran, N,N-dimethylformamide, and diethyl ether.

19. The method of claim 18, wherein, The mass ratio of the isoquinoline derivative to the first organic solvent is 1:2 to 10.

20. The method of claim 19, wherein, The mass ratio of the isoquinoline derivative to the first organic solvent is 1:3 to 8.

21. The method of making according to claim 5 or 6, wherein, In step S2, the first intermediate reacts with haloisoquinoline in a second organic solvent.

22. The method of claim 21, wherein, In step S2, the reaction temperature is 60–200°C.

23. The method of claim 22, wherein, The reaction temperature is 60℃~120℃.

24. The method of claim 21, wherein, The halogenated isoquinoline is 2-bromoisoquinoline.

25. The method of claim 24, wherein, The mass ratio of the first intermediate to 2-bromoisoquinoline is 1:1 to 3.

26. The method of claim 25, wherein, The mass ratio of the first intermediate to 2-bromoisoquinoline is 1:1 to 1.

5.

27. The method of claim 21, wherein, The second organic solvent is one or more of toluene, chloroform, dichloromethane, and tetrahydrofuran.

28. The method of claim 27, wherein, The mass ratio of the first intermediate to the second organic solvent is 1:2 to 10.

29. The method of claim 28, wherein, The mass ratio of the first intermediate to the second organic solvent is 1:4 to 6.

30. The method of making according to claim 5 or 6, wherein, In the step S3, the second intermediate reacts with an iron source containing Fe 2+ from a third organic solvent.

31. The method of claim 30, wherein, In step S3, the reaction temperature is 10–80°C.

32. The method of claim 31, wherein, The reaction temperature is 20℃~40℃.

33. The preparation method according to claim 30, characterized in that, The third organic solvent is one or more of N,N-dimethylformamide, dimethyl sulfoxide, methanol, and acetonitrile.

34. The preparation method according to claim 33, characterized in that, The mass ratio of the second intermediate to the third organic solvent is 1:1 to 10.

35. The preparation method according to claim 34, characterized in that, The mass ratio of the second intermediate to the third organic solvent is 1:2 to 4.

36. The use of the iron complex based on biisoquinoline as described in any one of claims 1-4 as a catalyst for the hydroxylation reaction of anisole.

37. The application according to claim 36, characterized in that, The anisole hydroxylation reaction is a reaction of anisole with an oxidant to prepare p-hydroxyanisole and concurrently produce o-hydroxyanisole.

38. The application according to claim 37, characterized in that, The oxidant is hydrogen peroxide with a mass concentration of 20-60%.

39. A method for preparing p-hydroxyanisole and concurrently producing o-hydroxyanisole, characterized in that, In the presence of a catalyst, anisole undergoes a hydroxylation reaction with an oxidant to prepare p-hydroxyanisole and co-produce o-hydroxyanisole, wherein the catalyst is an iron complex based on biisoquinoline as described in any one of claims 1-4.

40. The method according to claim 39, characterized in that, The amount of the catalyst used is 0.1% to 1.5% of anisole by mass percentage.

41. The method according to claim 40, characterized in that, The amount of catalyst used, by mass percentage, is 0.2% to 0.8% of anisole.

42. The method according to any one of claims 39-41, characterized in that, The oxidant is hydrogen peroxide with a mass concentration of 20-60%.

43. The method according to any one of claims 39-41, characterized in that, The hydroxylation reaction is carried out in a reaction solvent.

44. The method according to claim 43, characterized in that, The reaction solvent is one or more of acetone, methanol, water, and ethanol, and the mass ratio of anisole to the reaction solvent is 1:0.5 to 5.

45. The method according to claim 44, characterized in that, The mass ratio of anisole to reaction solvent is 1:0.5 to 1.

5.

46. ​​The method according to any one of claims 39-41, characterized in that, The hydroxylation reaction is carried out at a temperature of 50–80°C and at atmospheric pressure.

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