Synthetic method of isoquinoline

Abstract

The invention relates to the field of isoquinoline preparation, and discloses a synthesis method of isoquinoline. The method comprises the following steps: in the presence of a protective atmosphere and a first solvent, carrying out rearrangement oxidation reaction on 2-indanone oxime and a first catalyst to obtain isoquinolone, the first catalyst comprises a first carrier, a first active component and a first auxiliary component, and the first auxiliary component comprises a P element and a B element; the mass ratio of the element B to the element P is 1: (2-20); in the presence of a hydrogen atmosphere and a second solvent, carrying out hydrogenation reaction on isoquinolone and a second catalyst to obtain isoquinoline, the second catalyst comprises a second carrier, a second additive component and a second active component, and the second additive component comprises a Cu element and Cr; the mass ratio of the second auxiliary agent component to the second active component is 1: (0.01-1). According to the synthesis method, no strong acid is adopted, and the product yield is high.

Description

Technical Field

[0001] This invention relates to the field of isoquinoline preparation, and more specifically to a method for synthesizing isoquinolines. Background Technology

[0002] Isoquinoline is an important chemical product used in the manufacture of pharmaceuticals and highly effective insecticides. Its derivatives are used in the production of color films and dyes. The isoquinoline skeleton is widely found in natural products and pharmacologically active drug molecules, playing a vital role in the pharmaceutical and chemical industries. Traditional methods for synthesizing isoquinoline are gradually being phased out due to their long reaction times and demanding reaction conditions.

[0003] Traditional synthetic methods for isoquinolines include the Gabriel-Colman method, the Pomeranz-Fritsch method, the Bischler-Napieralski method, the Pictet-Spengler method, and the Pictet-Gams method. The Gabriel-Colman method uses phthalimide as a starting material, which rearranges in sodium ethoxide at 100°C to generate isoquinoline derivatives. Decarboxylation yields 1,4-dihydroxyisoquinoline. The Pomeranz-Fritsch method modifies this method by condensing an aromatic aldehyde with an aminoacetal. The Schlittler-Muller method uses diethoxyacetaldehyde and an aromatic methylamine to condense an imine, which is then cyclized to give a 1-substituted isoquinoline derivative. The resulting imine undergoes cyclization in an acidic environment to form isoquinoline. The yield of isoquinoline is higher when benzaldehyde has an electron-donating group, such as a methoxy group, at the meta or para position. The Bischler-Napieralski method involves reacting phenethylamine with carboxylic acids or acyl chlorides to generate amides, followed by dehydration and ring closure using dehydrating agents such as phosphorus pentoxide, phosphorus pentachloride, or phosphorus oxychloride to yield 1-substituted dihydroisoquinoline compounds, which are then dehydrogenated to generate 1-substituted isoquinoline compounds. The Pictet-Spengler method involves reacting aldehydes directly with phenethylamine followed by cyclization to obtain tetrahydroisoquinoline derivatives. The Pictet-Gams method uses phenylethanolamine as a starting material, converting it into an amide, which is then dehydrated and cyclized to obtain 1-substituted isoquinoline derivatives.

[0004] Traditional methods for preparing isoquinolines, such as the Gabriel-Colman and Pomeranz-Fritsch methods, require strong acids and bases, leading to isomer formation, low product purity, and environmental pollution. Subsequent research has utilized metal-catalyzed methods to prepare isoquinolines and their derivatives. These methods replace substrates such as aminoacetaldehyde and glyoxal with alkynes, diazonides, and vinyl acetate; the cyclization mechanism shifts from strong acid or strong base catalysis to metal catalysis. Compared to traditional methods, the improved reaction conditions are milder and more selective. However, these improved methods often employ homogeneous catalysis with noble metals, require the introduction of co-catalysts, and some utilize photocatalysis and microwave technology, presenting technical challenges and high costs for industrial application. The Bischler-Napieralski, Pictet-Spengler, and Pictet-Gams methods for preparing isoquinolines require strong dehydrating agents such as phosphorus pentoxide, phosphorus pentachloride, phosphorus oxychloride, concentrated sulfuric acid or fuming sulfuric acid, and acyl chlorides. These methods result in high production costs, generate significant amounts of waste, and cause environmental pollution. Summary of the Invention

[0005] The purpose of this invention is to overcome the problems of harsh reaction conditions, numerous byproducts, low product yield, and serious environmental pollution in existing methods for synthesizing isoquinolines, and to provide a method for synthesizing isoquinolines that does not use strong acids and has a high product yield.

[0006] This invention provides a method for synthesizing isoquinoline, the method comprising: (1) Under a protective atmosphere and in the presence of a first solvent, 2-indanone oxime is subjected to a rearrangement oxidation reaction with a first catalyst to obtain isoquinolone; The first catalyst includes a first support, a first active component, and a first auxiliary component. The first auxiliary component includes P and B elements, and the first active component is selected from at least one of Pd, Pt, Ru, Cu, Ni, Zn, Ce, Cr, and Fe elements. The mass ratio of element B to element P is 1:2-20; (2) In the presence of hydrogen atmosphere and second solvent, isoquinolone is hydrogenated with second catalyst to obtain isoquinoline; The second catalyst includes a second support, a second promoter component, and a second active component. The second promoter component includes Cu and Cr, and the second active component is selected from at least one of Ru, Ni, Co, La, and Fe. The mass ratio of the second auxiliary component to the second active component is 1:0.01-1.

[0007] Compared with the prior art, the present invention has the following beneficial effects through the above technical solution: (1) By selecting 2-indanone oxime as the reaction raw material and using a specific catalyst system, the generation of by-products in the preparation of isoquinoline is reduced, and the purity and yield of isoquinoline are significantly improved. (2) The reaction does not require strong acids, strong bases or strong dehydrating agents, and has few by-products and little waste residue, resulting in a significant reduction in the emission of waste gas, wastewater, and solid waste. (3) The synthesis of isoquinoline can be completed in two steps, and the route is simple and easy to operate; (4) The catalyst is stable and recyclable, suitable for fixed-bed continuous reaction, and easy to realize industrial scale-up production. Attached Figure Description

[0008] Figure 1 This is a schematic diagram of the technical route of the present invention. Detailed Implementation

[0009] The endpoints and any values ​​of the ranges disclosed herein are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of the various ranges, the endpoint values ​​of the various ranges and individual point values, and individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed herein.

[0010] In this invention, unless otherwise specified, the terms "first," "second," "third," "fourth," and "fifth" do not indicate a sequential order or limit the specific materials or steps; they are merely used to distinguish between different materials or steps. For example, in "first catalyst" and "second catalyst," "first" and "second" simply indicate that they are not the same catalyst; similarly, in "first active component" and "second active component," "first" and "second" simply indicate that they are not the same active component; in "first auxiliary component" and "second auxiliary component," "first" and "second" simply indicate that they are not the same auxiliary component; in "first solvent" and "second solvent," "first" and "second" simply indicate that they are not the same solvent; in "first support" and "second support," "first" and "second" simply indicate that they are not the same support. In "First Impregnation", "Second Impregnation", "Third Impregnation", and "Fourth Impregnation", "first" and "second", "third", and "fourth" are used only to indicate that they are not the same impregnation. In "First Firing", "Second Firing", "Third Firing", and "Fourth Firing", "first" and "second", "third", and "fourth" are used only to indicate that they are not the same firing. In "First Oxygen Atmosphere", "Second Oxygen Atmosphere", "Third Oxygen Atmosphere", "Fourth Oxygen Atmosphere", and "Fifth Oxygen Atmosphere", "first" and "second", "third", "fourth", and "fifth" are used only to indicate that they are not the same oxygen atmosphere.

[0011] In this invention, the first auxiliary component precursor, the first active component precursor, the second auxiliary component precursor, and the second active component precursor can be any soluble compound that can be obtained by calcination of the corresponding component elements, and this invention does not have any particular limitation on this.

[0012] The present invention has a wide range of solvent selection for solutions containing the first auxiliary component precursor, solutions containing the first active component precursor, solutions containing the second auxiliary component precursor, and solutions containing the second active component precursor. As long as the solvent can dissolve the precursor of the corresponding component element, the present invention does not have any particular limitation. For example, it can be water.

[0013] In this invention, unless otherwise stated, room temperature or normal temperature refers to 25±2℃.

[0014] This invention provides a method for synthesizing isoquinoline, the method comprising: (1) Under a protective atmosphere and in the presence of a first solvent, 2-indanone oxime is subjected to a rearrangement oxidation reaction with a first catalyst to obtain isoquinolone; The first catalyst includes a first support, a first active component, and a first auxiliary component. The first auxiliary component includes P and B elements, and the first active component is selected from at least one of Pd, Pt, Ru, Cu, Ni, Zn, Ce, Cr, and Fe elements. The mass ratio of element B to element P is 1:2-20; (2) In the presence of hydrogen atmosphere and second solvent, isoquinolone is hydrogenated with second catalyst to obtain isoquinoline; The second catalyst includes a second support, a second promoter component, and a second active component. The second promoter component includes Cu and Cr, and the second active component is selected from at least one of Ru, Ni, Co, La, and Fe. The mass ratio of the second auxiliary component to the second active component is 1:0.01-1.

[0015] In this invention, 2-indanone oxime is selected as the reactant, providing a novel reaction route. In the first step, the first active component and the first promoter component in the catalyst enable oxime rearrangement and dehydrogenation, efficiently converting 2-indanone oxime to isoquinolone. In the second step, the second promoter component in the catalyst enables dehydroxylation of the isoquinolone, efficiently converting it to isoquinoline, while suppressing side reactions such as excessive hydrogenation. This two-step "rearrangement oxidation-hydrogenation" method avoids the traditional conditions of strong acids, strong bases, and strong dehydrating agents, resulting in fewer byproducts, higher product yields, and achieving green synthesis.

[0016] It should be noted that, in this invention, the first active component and the first auxiliary component exist in the form of elements or oxides, and at least partially exist in the form of oxides.

[0017] In this invention, the second auxiliary component and the second active component exist in the form of elements or oxides, and at least partially in the form of elements.

[0018] According to the present invention, preferably, the first active component and the second active component are of different types.

[0019] The present invention has a wide range of choices for the carrier. Preferably, the first carrier is selected from at least one of Hβ, HY, HZSM-5, MCM-41, SBA-15, diatomaceous earth, and γ-Al2O3, and more preferably γ-Al2O3 and / or HY.

[0020] According to the present invention, the mass ratio of element B to element P is 1:2-20, for example, it can be 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12, 1:13, 1:14, 1:15, 1:16, 1:17, 1:18, 1:19, 1:20, and any value within the range of any two values, preferably 1:5-10.

[0021] In this invention, the first auxiliary component consists of elements B and P, and the ratio meets the above-mentioned preferred range. This enhances the acidity and stability of the catalyst, and is more conducive to promoting the dehydration and rearrangement of 2-indanone oxime, thereby improving the selectivity of isoquinolones.

[0022] According to the present invention, preferably, based on the total mass of the first catalyst, the content of the first support is 50-99 wt%, more preferably 70-99 wt%; based on metal elements, the content of the first active component is 0.1-15 wt%, more preferably 0.5-6 wt%; based on non-metal elements, the content of the first auxiliary component is 0.1-20 wt%, more preferably 1-15 wt%.

[0023] In this invention, the content of each component in the first catalyst meets the above-mentioned preferred range, which can form a large number of effective active sites, while avoiding the aggregation and deactivation of active components due to excessive loading, thereby improving the yield of isoquinolone.

[0024] According to the present invention, preferably, the first active component is selected from at least one of Pt, Pd, and Ru, more preferably Pd. Based on the total amount of the first catalyst, the content of the first active component, calculated in terms of metal elements, is 0.1-5 wt%, more preferably 0.5-5 wt%, which is more conducive to the rearrangement reaction.

[0025] Alternatively, according to the present invention, preferably, the first active component is selected from at least one of Cu, Ni, Zn, Ce, Cr, and Fe, more preferably Fe, and the content of the first active component is 0.1-10 wt% based on the total amount of the first catalyst and calculated as a metal element.

[0026] According to a preferred embodiment of the present invention, the first active component is selected from at least one of Pt, Pd, and Ru elements, and at least one of Cu, Ni, Zn, Ce, Cr, and Fe elements, preferably Pd and Fe elements.

[0027] More preferably, the mass ratio of Fe to Pd is 1:0.25-10, for example, it can be 1:0.5, 1:1, 1:1.5, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, 1:5.5, 1:6, 1:6.5, 1:7, 1:7.5, 1:8, 1:8.5, 1:9, 1:9.5, 1:10, or any value within the range of any two values.

[0028] In this invention, the type and content of the first active component meet the above-mentioned preferred range, which is beneficial to further improve the yield of isoquinolone.

[0029] The present invention allows for a wide range of selection for the mass ratio of 2-indanone oxime to the first catalyst. Preferably, the mass ratio of 2-indanone oxime to the first catalyst is 1:0.05-2, more preferably 1:0.1-0.5, which is more conducive to ensuring that the catalyst has sufficient active sites to contact the reactants and promotes complete reaction.

[0030] According to the present invention, preferably, the ratio of the first solvent to 2-indanone oxime is 5-20 mL:1 g, more preferably 8-10 mL:1 g.

[0031] The present invention has a wide range of solvents that can be selected. Preferably, the first solvent is selected from toluene and / or ethylbenzene.

[0032] The present invention has a wide range of protective atmospheres to choose from, and preferably, the protective atmosphere is nitrogen.

[0033] The present invention allows for a wide range of methods for preparing the first catalyst. Preferably, the method for preparing the first catalyst includes: (S1) The solution containing the precursor of the first auxiliary component is first impregnated with the first carrier, and then calcined in the first oxygen-containing atmosphere; (S2) The solution containing the first active component precursor is impregnated with the product in step (S1) for a second time, and then calcined in a second oxygen-containing atmosphere.

[0034] In this invention, the first catalyst is prepared by the above method. The support is first modified by the first auxiliary component, and then the first active component is introduced. This can provide stable acid centers, which is beneficial for providing reaction sites for rearrangement reactions.

[0035] According to the present invention, preferably, the amounts of the first auxiliary component precursor, the first support, and the first active component precursor are such that, based on the total mass of the first catalyst, the content of the first support is 50-99 wt%, more preferably 70-99 wt%; the content of the first active component, calculated as metal elements, is 0.1-15 wt%, more preferably 0.5-6%; and the content of the first auxiliary component, calculated as non-metal elements, is 0.1-20 wt%, more preferably 1-15 wt%.

[0036] According to the present invention, preferably, the amounts of the first auxiliary component precursor, the first support and the first active component precursor are such that the first active component is selected from at least one of Pt, Pd and Ru elements, and the content of the first active component is 0.1-5 wt% based on the total amount of the first catalyst and calculated as a metal element, more preferably 0.5-5 wt%.

[0037] Alternatively, the amounts of the first auxiliary component precursor, the first support, and the first active component precursor are such that the first active component is selected from at least one of Cu, Ni, Zn, Ce, and Cr elements, and the content of the first active component is 0.1-10 wt% based on the total amount of the first catalyst and calculated as a metal element.

[0038] According to the present invention, preferably, the conditions for the first impregnation include: a temperature of 25-80°C, more preferably 25-50°C; and a time of 2-12 hours, more preferably 2-6 hours.

[0039] According to the present invention, preferably, the first oxygen-containing atmosphere is air.

[0040] According to the present invention, preferably, the conditions for the first calcination include: a temperature of 200-600°C, more preferably 300-500°C; and a time of 2-8 hours, more preferably 3-5 hours.

[0041] According to the present invention, preferably, the conditions for the second impregnation include: a temperature of 25-80°C, more preferably 25-50°C; and a time of 2-6 hours, more preferably 3-5 hours.

[0042] According to the present invention, preferably, the second oxygen-containing atmosphere is air.

[0043] According to the present invention, preferably, the conditions for the second calcination include: a temperature of 200-700°C, more preferably 300-600°C; and a time of 2-8 hours, more preferably 3-5 hours.

[0044] In this invention, the first and second impregnations are each followed by drying independently, as long as the solvent can be removed. The drying conditions in this invention are not particularly limited, and those skilled in the art can select them according to actual needs.

[0045] According to the present invention, preferably, the conditions for the rearrangement oxidation reaction include a temperature of 120-300°C, more preferably 150-250°C.

[0046] According to the present invention, preferably, the rearrangement oxidation reaction conditions include a time of 4-12 hours, more preferably 6-10 hours.

[0047] In this invention, the rearrangement oxidation reaction conditions within the above-mentioned preferred range can ensure complete reaction of the raw materials and minimize side reactions, which is beneficial to improving the reaction yield.

[0048] In this invention, the rearrangement oxidation reaction also includes filtration, vacuum concentration, and purification.

[0049] The present invention does not particularly limit the filtration method, as long as it can filter the catalyst, and those skilled in the art can choose according to actual needs.

[0050] This invention does not particularly limit the method of vacuum concentration, as long as the solvent can be removed. Those skilled in the art can choose according to actual needs.

[0051] The present invention does not particularly limit the purification method, as long as the isoquinolone can be purified. Those skilled in the art can choose according to actual needs, such as chromatography separation.

[0052] According to the present invention, preferably, the mass ratio of isoquinolone to the second catalyst is 1:0.02-2, more preferably 1:0.1-0.5, which can reduce side reactions and is more conducive to improving the reaction yield.

[0053] According to the present invention, preferably, the ratio of the second solvent to the isoquinolone is 2-20 mL: 1 g, more preferably 2-10 mL: 1 g.

[0054] The present invention has a wide range of choices for the second solvent. Preferably, the second solvent is selected from at least one of benzene, toluene, o-xylene, m-xylene, p-xylene, chlorobenzene, o-dichlorobenzene, p-dichlorobenzene, n-heptane, n-hexane, and cyclohexane, and more preferably toluene.

[0055] According to the present invention, preferably, the second carrier is selected from at least one of Hβ, HY, HZSM-5, MCM-41, SBA-15, and γ-Al2O3, more preferably from at least one of γ-Al2O3, HY, and HZSM-5.

[0056] According to the present invention, the mass ratio of Cu to Cr is 1:0.01-1, preferably 1:0.2-0.5.

[0057] In this invention, the second auxiliary component consists of Cu and Cr elements, and satisfies the above-mentioned preferred range. The two work synergistically to have high activity in the selective hydrogenation and deoxygenation of carbonyl groups, and can effectively convert the lactam structure of isoquinolone into isoquinoline.

[0058] According to the present invention, preferably, the second active component is Ru, which is beneficial for converting the lactam structure of isoquinolone into isoquinoline.

[0059] According to the present invention, preferably, based on the total mass of the second catalyst, the content of the second support is 50-99 wt%, more preferably 70-99 wt%; based on metal elements, the content of the second active component is 0.1-10 wt%, more preferably 0.2-5 wt%; based on metal elements, the content of the second auxiliary component is 0.1-20 wt%, more preferably 1-20 wt%.

[0060] In this invention, the content of each component in the second catalyst meets the above-mentioned preferred range, which can ensure synergistic catalytic reduction and is beneficial to improving the yield of isoquinoline.

[0061] According to the present invention, preferably, the method for preparing the second catalyst includes: (Q1) The solution containing the precursor of the second auxiliary component is impregnated with the second carrier in a third impregnation, and then calcined in a third oxygen-containing atmosphere; (Q2) The solution containing the precursor of the second active component is impregnated with the product in step (Q1) for a fourth time, then calcined in a fourth oxygen-containing atmosphere, reduced in a hydrogen atmosphere, and passivated in a fifth oxygen-containing atmosphere.

[0062] According to the present invention, preferably, the amounts of the second auxiliary component precursor, the second support, and the second active component precursor are such that, based on the total mass of the second catalyst, the content of the second support is 50-99 wt%, more preferably 70-99 wt%; the content of the second active component, calculated in terms of metal elements, is 0.1-10 wt%, more preferably 0.2-5 wt%; and the content of the second auxiliary component, calculated in terms of metal elements, is 0.1-20 wt%, more preferably 1-20 wt%.

[0063] According to the present invention, preferably, the conditions for the third impregnation include: a temperature of 25-80°C, more preferably 25-50°C; and a time of 2-8 hours, more preferably 2-5 hours.

[0064] According to the present invention, preferably, the third oxygen-containing atmosphere is air.

[0065] According to the present invention, preferably, the conditions for the third calcination include: a temperature of 400-600℃, more preferably 500-600℃; and a time of 2-6h, more preferably 3-5h.

[0066] According to the present invention, preferably, the conditions for the fourth impregnation include: a temperature of 25-80°C, more preferably 25-50°C; and a time of 2-8 hours, more preferably 2-5 hours.

[0067] According to the present invention, preferably, the fourth oxygen-containing atmosphere is air.

[0068] According to the present invention, preferably, the conditions for the fourth calcination include: a temperature of 350-600°C, more preferably 400-600°C; and a time of 2-8 hours, more preferably 3-5 hours.

[0069] In this invention, the third and fourth impregnations are each followed by drying independently, as long as the solvent can be removed. The drying conditions are not particularly limited in this invention, and those skilled in the art can select them according to actual needs.

[0070] According to the present invention, preferably, the reduction conditions include: a temperature of 250-500°C, more preferably 250-400°C; and a time of 2-8 hours, more preferably 2-6 hours.

[0071] According to the present invention, preferably, the fifth oxygen-containing atmosphere is O2 and N2.

[0072] According to the present invention, preferably, based on the volume of the fifth oxygen-containing atmosphere, the O2 content is 1-2% by volume and the N2 content is 98-99% by volume.

[0073] In this invention, the use of the aforementioned fifth oxygen-containing atmosphere can passivate the catalyst surface, which is beneficial to improving the stability of the catalyst.

[0074] It should be noted that the "passivation" mentioned in this invention refers to the passivation of the surface metal of the catalyst, which facilitates the use of the catalyst.

[0075] According to the present invention, preferably, the conditions for the hydrogenation reaction include a temperature of 150-500°C, more preferably 200-300°C.

[0076] According to the present invention, preferably, the conditions for the hydrogenation reaction include a time of 2-12 hours, more preferably 4-8 hours.

[0077] According to the present invention, preferably, the conditions for the hydrogenation reaction include a pressure of 1-8 MPa, more preferably 4-8 MPa.

[0078] In this invention, using hydrogenation conditions within the above-mentioned preferred range is more conducive to improving the yield of isoquinoline.

[0079] In this invention, the hydrogenation reaction also includes filtration, vacuum concentration, and purification.

[0080] The present invention does not particularly limit the filtration method, as long as it can filter the catalyst, and those skilled in the art can choose according to actual needs.

[0081] This invention does not particularly limit the method of vacuum concentration, as long as the solvent can be removed. Those skilled in the art can choose according to actual needs.

[0082] The present invention does not particularly limit the purification method, as long as isoquinoline can be purified. Those skilled in the art can choose according to actual needs, such as chromatography separation.

[0083] The present invention will be described in detail below through embodiments.

[0084] Unless otherwise specified, all examples and comparative examples below are conventional methods; the reagents, materials and instruments used are commercially available and / or prepared using methods known in the art, unless otherwise specified.

[0085] In the following examples and comparative examples, the yield of isoquinolone = mass of isoquinolone / (mass of indanone oxime / 147.18 × 145.16).

[0086] In the following examples and comparative examples, the yield of isoquinoline = mass of isoquinoline / (mass of isoquinolone / 145.16 × 129.16).

[0087] The following preparation examples illustrate the preparation of the first catalyst in this invention.

[0088] Preparation Examples A1-A6 and Comparative Preparation Examples DA1-DA3 The first auxiliary component precursor was dissolved in 10g of deionized water at the appropriate amount, such that the contents of P and B elements in the prepared catalyst met the requirements of Table 1. 10g of support was added and impregnated for 2h, then dried at 120℃ for 2h, and then calcined at 500℃ in air for 4h to complete the first support modification. The first active component precursor was dissolved in 10g of deionized water at the appropriate amount, such that the contents of the first active component in the prepared catalyst met the requirements of Table 1. The first modified support was added and impregnated for 2h, then dried at 120℃ for 2h, and then calcined at 500℃ in air for 4h.

[0089] Table 1

[0090] Note: The remaining amount in the table represents the mass percentage of the support in the first catalyst.

[0091] The following preparation examples illustrate the preparation of the second catalyst in this invention.

[0092] Preparation Examples B1-B6 and Comparative Preparation Examples DB1-DB3 The second auxiliary component precursor was dissolved in 10g of deionized water at the appropriate amount, ensuring that the second auxiliary component in the prepared catalyst met the requirements of Table 2. 10g of support was added and impregnated for 2 hours, then dried at 120℃ for 2 hours, and finally calcined at 550℃ in air for 4 hours to complete the first support modification. The second active component precursor was dissolved in 10g of deionized water at the appropriate amount, ensuring that the second active component in the prepared catalyst met the requirements of Table 2. The first modified support was added and impregnated for 2 hours, then dried at 120℃ for 2 hours, and finally calcined at 550℃ in air for 6 hours. After calcination, the catalyst was reduced at 250℃ in hydrogen atmosphere for 4 hours, and finally passivated by introducing 1% O2 / N2 at room temperature for 12 hours.

[0093] Table 2

[0094] Note: The remaining amount in the table represents the mass percentage of the support in the first catalyst.

[0095] The following examples illustrate the method for synthesizing isoquinoline in this invention.

[0096] Examples 1-2 Synthesis of isoquinoline (product 3a): As shown in Table 3, 2-indanone oxime (1a, 2.1g) and the first catalyst (catalyst numbers shown in Table 3) (0.21g) were added to toluene (21mL), and the mixture was heated to 200℃ and reacted for 7 hours. After the reaction was complete, the catalyst was filtered, the solvent was removed by concentration under reduced pressure, and the product was purified by column chromatography to obtain a light brown solid isoquinolone (2a). Isoquinolone (2a, 2g), the second catalyst (catalyst numbers shown in Table 3) (0.2g), and toluene (4mL) were reacted under a hydrogen atmosphere at 200℃ and 4MPa for 5 hours. After the reaction was complete, the catalyst was filtered, the solvent was removed, and the product was purified by column chromatography to obtain a pale yellow oil, which was pure isoquinoline (3a).

[0097] Following the above implementation method, and as shown in Table 3, the above catalysts were selected respectively, and the synthesis routes are as follows: Figure 1 As shown, where, Figure 1 Catalyst A is the first catalyst, catalyst B is the second catalyst, solvent A is the first solvent, and solvent B is the second solvent. The reaction results are shown in Table 3.

[0098] The yields of isoquinolones and isoquinolines are shown in Table 3; The yield of isoquinolone = mass of isoquinolone / (mass of indanone oxime / 147.18 × 145.16).

[0099] The yield of isoquinoline = mass of isoquinoline / (mass of isoquinolone / 145.16 × 129.16).

[0100] Example 3 Synthesis of isoquinoline (product 3a): 2-Indanone oxime (1a, 2.1 g) and catalyst A3 (1.05 g) were added to toluene (21 mL), and the mixture was heated to 180 °C and reacted for 10 hours. After the reaction was complete, the catalyst was filtered off, the solvent was removed by concentration under reduced pressure, and the product was purified by column chromatography to obtain a light brown solid isoquinolone (2a). Isoquinolone (2a, 2 g), catalyst B3 (1 g), and toluene (4 mL) were then reacted at 220 °C and 5 MPa for 8 hours under a hydrogen atmosphere. After the reaction was complete, the catalyst was filtered off, the solvent was removed, and the product was purified by column chromatography to obtain a pale yellow oil, which was the pure isoquinoline (3a). The reaction results are shown in Table 3.

[0101] Examples 4-6 Synthesis of isoquinoline (product 3a): 2-Indanone oxime (1a, 2.1g) and the first catalyst (catalyst numbers shown in Table 3) (0.21g) were added to toluene (21mL), and the mixture was heated to 200℃ and reacted for 7 hours. After the reaction was complete, the catalyst was filtered off, the solvent was removed by concentration under reduced pressure, and the product was purified by column chromatography to obtain a light brown solid isoquinolone (2a). Isoquinolone (2a, 2g), the second catalyst (catalyst numbers shown in Table 3) (1g), and toluene (4mL) were reacted under a hydrogen atmosphere at 220℃ and 5MPa for 8 hours. After the reaction was complete, the catalyst was filtered off, the solvent was removed, and the product was purified by column chromatography to obtain a pale yellow oil, which was the pure isoquinoline (3a). The reaction results are shown in Table 3.

[0102] Comparative Examples 1-3 Synthesis of isoquinoline (product 3a): 2-Indanone oxime (1a, 2.1g) and the first catalyst (catalyst numbers shown in Table 3) (0.21g) were added to toluene (21mL), and the mixture was heated to 200℃ and reacted for 7 hours. After the reaction was complete, the catalyst was filtered off, the solvent was removed by concentration under reduced pressure, and the product was purified by column chromatography to obtain a light brown solid isoquinolone (2a). Isoquinolone (2a, 2g), the second catalyst (catalyst numbers shown in Table 3) (1g), and toluene (4mL) were reacted under a hydrogen atmosphere at 220℃ and 5MPa for 8 hours. After the reaction was complete, the catalyst was filtered off, the solvent was removed, and the product was purified by column chromatography to obtain a pale yellow oil, which was the pure isoquinoline (3a). The reaction results are shown in Table 3.

[0103] Table 3

[0104] The results show that, compared with the comparative example, the method provided by the present invention can synthesize isoquinoline in two steps without the need for strong acids, strong bases or strong dehydrating agents, and the yield is high. This solves the problems of harsh reaction conditions, many by-products, low product yield and serious environmental pollution in the existing methods for synthesizing isoquinoline.

[0105] The preferred embodiments of the present invention have been described in detail above; however, the present invention is not limited thereto. Within the scope of the inventive concept, various simple modifications can be made to the technical solutions of the present invention, including combinations of various technical features in any other suitable manner. These simple modifications and combinations should also be considered as the content disclosed in the present invention and are all within the protection scope of the present invention.

Claims

1. A method for synthesizing isoquinoline, characterized in that, The method includes: (1) Under a protective atmosphere and in the presence of a first solvent, 2-indanone oxime is subjected to a rearrangement oxidation reaction with a first catalyst to obtain isoquinolone; The first catalyst includes a first support, a first active component, and a first auxiliary component. The first auxiliary component includes P and B elements, and the first active component is selected from at least one of Pd, Pt, Ru, Cu, Ni, Zn, Ce, Cr, and Fe elements. The mass ratio of element B to element P is 1:2-20; (2) In the presence of hydrogen atmosphere and second solvent, isoquinolone is hydrogenated with second catalyst to obtain isoquinoline; The second catalyst includes a second support, a second promoter component, and a second active component. The second promoter component includes Cu and Cr, and the second active component is selected from at least one of Ru, Ni, Co, La, and Fe. The mass ratio of the second auxiliary component to the second active component is 1:0.01-1.

2. The synthesis method according to claim 1, wherein, The first carrier is selected from at least one of Hβ, HY, HZSM-5, MCM-41, SBA-15, diatomaceous earth, and γ-Al2O3; The mass ratio of element B to element P is 1:5-10.

3. The synthesis method according to claim 1, wherein, Based on the total mass of the first catalyst, the content of the first support is 50-99 wt%, the content of the first active component is 0.1-15 wt% based on metal elements, and the content of the first auxiliary component is 0.1-20 wt% based on non-metal elements.

4. The synthesis method according to claim 1, wherein, The first active component is selected from at least one of Pt, Pd, and Ru elements, and its content, based on the total amount of the first catalyst and calculated as a metal element, is 0.1-5 wt%. Alternatively, the first active component is selected from at least one of Fe, Cu, Ni, Zn, Ce, and Cr elements, and the content of the first active component is 0.1-10 wt% based on the total amount of the first catalyst and calculated as a metal element.

5. The synthesis method according to claim 1, wherein, The mass ratio of 2-indanone oxime to the first catalyst is 1:0.05-2; The ratio of the first solvent to 2-indanone oxime is 5-20 mL: 1 g.

6. The synthesis method according to claim 1, wherein, The preparation method of the first catalyst includes: (S1) The solution containing the precursor of the first auxiliary component is first impregnated with the first carrier, and then calcined in the first oxygen-containing atmosphere; (S2) The solution containing the first active component precursor is impregnated with the product in step (S1) for a second time, and then calcined in a second oxygen-containing atmosphere.

7. The synthesis method according to claim 1, wherein, The conditions for the rearrangement oxidation reaction include: a temperature of 120-300℃ and a time of 4-12h.

8. The synthesis method according to any one of claims 1-7, wherein, The mass ratio of isoquinolone to the second catalyst is 1:0.02-2; The ratio of the second solvent to isoquinolone is 2-20 mL: 1 g.

9. The synthesis method according to any one of claims 1-7, wherein, The second support is selected from at least one of Hβ, HY, HZSM-5, MCM-41, SBA-15, and γ-Al2O3; The mass ratio of Cu to Cr is 1:0.2-0.5; The second active component is Ru.

10. The synthesis method according to any one of claims 1-7, wherein, Based on the total mass of the second catalyst, the content of the second support is 50-99 wt%, the content of the second active component is 0.1-10 wt% based on metal elements, and the content of the second auxiliary component is 0.1-20 wt% based on metal elements.

11. The synthesis method according to any one of claims 1-7, wherein, The preparation method of the second catalyst includes: (Q1) The solution containing the precursor of the second auxiliary component is impregnated with the second carrier in a third impregnation, and then calcined in a third oxygen-containing atmosphere; (Q2) The solution containing the precursor of the second active component is impregnated with the product in step (Q1) for a fourth time, then calcined in a fourth oxygen-containing atmosphere, reduced in a hydrogen atmosphere, and passivated in a fifth oxygen-containing atmosphere.

12. The synthesis method according to any one of claims 1-7, wherein, The conditions for the hydrogenation reaction include: temperature of 150-500℃; time of 2-12h; and pressure of 1-8MPa.

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