A process for the direct preparation of semi-hydrogenated nitrogen-containing aromatic heterocyclic compounds from sugars

Abstract

The present application relates to chemical synthesis technology, and aims to provide a method for directly preparing semi-hydrogenated nitrogen-containing aromatic heterocyclic compounds from sugar. Sugar, 1,2-aromatic diamine, metal catalyst, water, or further adding inorganic base, stirring uniformly; hydrothermal reaction is carried out in hydrogen atmosphere; after the reaction is completed, the organic phase layer is collected and extracted, separated and purified, and brown or brown oil liquid is obtained, which is semi-hydrogenated nitrogen-containing aromatic heterocyclic compound. The present application directly uses renewable and large amount of cheap and easily available sugar as the reaction raw material, avoids directly using non-renewable and expensive petroleum-based platform compounds; the reaction uses environmentally friendly water as the solvent and uses recyclable heterogeneous metal catalyst, so that the reaction method is green and environmentally friendly, and the cost is lower; the one-step synthesis method under relatively mild conditions is simple in process and simple in reaction steps, and the reaction equipment is simple and easy to operate; the present application has wide applicability, high reaction efficiency and recyclable and reusable catalyst.

Description

Technical Field

[0001] The present invention relates to chemical synthesis technology, and in particular to a novel method for synthesizing semi-hydrogenated nitrogen-containing aromatic heterocycles from renewable biomass resources, and specifically to a method for converting sugars into semi-hydrogenated nitrogen-containing aromatic heterocycles (including 1,2,3,4-tetrahydroquinoxaline derivatives) in a one-step process using a heterogeneous metal catalyst. Background Art

[0002] Semi-hydrogenated nitrogen-containing aromatic heterocyclic compounds (including 1,2,3,4-tetrahydroquinoxaline derivatives) are an important class of heterocyclic compounds. They are widely present in numerous biologically active natural products, pharmaceuticals, and dyes. For example, they are widely used as prostaglandin D2 receptor antagonists, vasopressin V2 receptor selective antagonists, bromodomain inhibitors, and azo dyes. Currently, the synthesis of 1,2,3,4-tetrahydroquinoxaline derivatives relies primarily on the selective semi-hydrogenation of benzodiazepine heterocycles (such as quinoxaline and quinoxalinone). The synthesis process typically employs a two-step reaction route, using expensive and difficult-to-obtain functionalized platform compounds as starting materials, such as 1,2-dicarbonyls, α-bromoketones, and α-ketoesters. These platform chemicals are currently primarily obtained from petroleum resources through multi-step, energy-intensive reactions and tedious purification processes. Notably, due to their high reactivity, the storage and transportation costs of these petroleum-based functionalized platform chemicals are also high. To synthesize 1,2,3,4-tetrahydroquinoxaline derivatives, these platform chemicals are typically first cyclized with aryl-1,2-diamines in an organic solvent to yield quinoxaline or quinoxalinone products. These products are then isolated and purified before undergoing catalytic reduction using noble metals or strong Lewis acid catalysts to ultimately convert them into the desired 1,2,3,4-tetrahydroquinoxaline derivatives.

[0003] Biomass is a widely available renewable resource on Earth. Effectively utilizing biomass as a carbon resource to develop high-value chemicals is of vital scientific and practical significance for addressing the depletion of Earth's petroleum resources and the resulting environmental pollution. Carbohydrates are the primary components of biomass resources. Efficiently utilizing carbohydrate sugars for the synthesis of chemicals, particularly high-value nitrogen-containing chemicals, is crucial for building a society less dependent on petroleum. Although many semi-hydrogenated nitrogen-containing aromatic heterocycles can be synthesized via a two-step process using expensive petroleum-based functionalized platform compounds, a green, one-step synthesis method that directly and efficiently converts abundant and renewable carbohydrate sugars into high-value semi-hydrogenated nitrogen-containing aromatic heterocycles in aqueous solution holds immense scientific, economic, and societal significance. This one-step synthesis utilizes inexpensive, renewable sugars as starting materials, avoids the purification of reaction intermediates, and avoids the use of environmentally harmful organic solvents. Therefore, this method offers advantages such as simplicity, low cost, and environmental friendliness.

[0004] To date, there has been no report on the catalytic conversion of renewable sugars (12≥C≥3) into semi-hydrogenated nitrogen-containing aromatic heterocyclic compounds via a one-step reaction. Summary of the Invention

[0005] The technical problem to be solved by the present invention is to overcome the deficiencies in the prior art and provide a method for directly preparing semi-hydrogenated nitrogen-containing aromatic heterocyclic compounds from sugars.

[0006] To solve the technical problem, the solution of the present invention is:

[0007] Provided is a method for directly preparing a semi-hydrogenated nitrogen-containing aromatic heterocyclic compound from sugar, which uses sugar and 1,2-aromatic diamine as starting materials, water as solvent, and in the presence of a metal catalyst and hydrogen to prepare the semi-hydrogenated nitrogen-containing aromatic heterocyclic compound through the following reaction:

[0008]

[0009] In the above formula: Ring A in 1,2-aromatic diamine is phenyl, naphthyl or pyridyl, R 1 is one or more of hydrogen, alkyl, alkoxy, and halogen; in the reaction product, R 2 、R 3 are the same or different substituent groups selected from hydrogen or methyl; or, an inorganic base is further added to the reaction raw materials to improve the selectivity of the reaction.

[0010] As a preferred embodiment of the present invention, the sugar is any one of the following: glucose, sucrose, glyceraldehyde, cellobiose, acetol, fructose, galactose, sorbose, tagatose, mannose, xylose, maltose or erythrose.

[0011] As a preferred embodiment of the present invention, the 1,2-aromatic diamine is any one of the following: o-phenylenediamine, 4,5-dimethyl-o-phenylenediamine, 4,5-difluoro-o-phenylenediamine, 4,5-dichloro-o-phenylenediamine, 2,3-naphthalene diamine, 4-methyl-o-phenylenediamine, 4-methoxy-o-phenylenediamine, 4-fluoro-o-phenylenediamine, 4-chloro-o-phenylenediamine or 2,3-diaminopyridine.

[0012] As a preferred embodiment of the present invention, an inorganic base is further added to the reactants to improve the selectivity of the reaction, and the inorganic base is any one of the following: potassium carbonate (K2CO3), sodium carbonate (Na2CO3), rubidium carbonate (Rb2CO3) or cesium carbonate (Cs2CO3).

[0013] As a preferred embodiment of the present invention, the catalyst is a heterogeneous catalyst, including a zeolite molecular sieve, a metal oxide or activated carbon as a carrier, and a single metal as the active center of the catalyst; the metal is selected from any one of Pt, Pd, Rh, Ir, and Ni, and the carrier is selected from any one of Beta molecular sieve, MOR molecular sieve, ZSM-5 molecular sieve, cerium dioxide (CeO2), titanium dioxide (TiO2), aluminum oxide (Al2O3), zirconium dioxide (ZrO2), silicon dioxide (SiO2) or activated carbon; in the catalyst, the content of the single metal is 0.5 to 3 wt%.

[0014] As a preferred embodiment of the present invention, the method specifically comprises the following steps:

[0015] (1) adding sugar, 1,2-aromatic diamine, metal catalyst and water into an autoclave, or further adding an inorganic base, and then stirring uniformly; controlling the amount of raw materials added so that the initial mixture of the reaction system has the following molar concentrations: sugar 0.01 to 0.1 mol / L; 1,2-aromatic diamine 0.02 to 1 mol / L; metal catalyst 0.1 to 1 mol%; and inorganic base 0 to 13 mmol / L;

[0016] (2) sealing the autoclave and conducting a hydrothermal reaction in a hydrogen atmosphere at 1-5 MPa; controlling the reaction temperature to 100-220° C. and the reaction time to 3-24 h under stirring;

[0017] (3) After the reaction is completed, the organic phase is collected and extracted to obtain a crude product; the crude product is separated and purified to obtain a brown or brown oily liquid, which is a semi-hydrogenated nitrogen-containing aromatic heterocyclic compound.

[0018] As a preferred embodiment of the present invention, in the step (3), after the organic phase layer is extracted with an organic solvent, the solvent is removed under reduced pressure to obtain a crude product.

[0019] As a preferred embodiment of the present invention, in step (3), the crude reaction product is separated by silica gel column chromatography to obtain a purified product.

[0020] Description of the invention principle:

[0021] Traditional methods for synthesizing 1,2,3,4-tetrahydroquinoxaline derivatives typically require obtaining functionalized platform compounds such as 1,2-dicarbonyls, α-bromoketones, and α-ketoesters as starting materials. These are then reacted with o-phenylenediamine to produce the quinoxaline or quinoxalinone products. The resulting products are then isolated and purified, followed by further catalytic reduction using noble metals or strong Lewis acid catalysts to ultimately reduce them to the desired 1,2,3,4-tetrahydroquinoxaline derivatives. The production of these functionalized platform compounds, such as those required for 1,2-dicarbonyls, α-bromoketones, and α-ketoesters, typically relies on traditional petroleum-based reaction routes. These routes often involve multiple, energy-intensive chemical reactions, multiple product separation and purification steps, and the use of toxic organic solvents, resulting in significant economic and environmental costs. For example, the synthesis of methylglyoxal from petroleum-derived propane typically requires five reaction steps. The five-step reaction includes first converting propane into propylene through a dehydrogenation reaction, then hydrochlorinating propylene to produce propylene chlorohydrin, then removing hydrogen chloride from propylene chlorohydrin to produce propylene oxide, and then hydrolyzing propylene oxide under acidic conditions to produce 1,2-propylene glycol, and finally catalytically dehydrogenating the propylene oxide over a high-temperature Ag-based catalyst to produce the desired methylglyoxal.

[0022] This invention proposes a method for synthesizing 1,2,3,4-tetrahydroquinoxaline derivatives or similar semi-hydrogenated nitrogen-containing aromatic heterocyclic compounds by adding sugars and 1,2-aromatic diamines to an aqueous solution and then catalyzing them with a recyclable heterogeneous metal hydrogenation catalyst. The addition of an inorganic base allows for highly selective synthesis of 2-methyl-1,2,3,4-tetrahydroquinoxaline products. The specific reaction process of this invention involves first converting sugars into highly reactive ortho-dicarbonyl compounds, including glyoxal, methylglyoxal, and diacetyl, with the assistance of 1,2-aromatic diamines. The resulting ortho-dicarbonyl compounds rapidly undergo condensation reactions with 1,2-aromatic diamines to form stable quinoxaline products. The quinoxaline products are then catalytically reduced to the corresponding 1,2,3,4-tetrahydroquinoxaline derivatives or similar semi-hydrogenated nitrogen-containing aromatic heterocyclic products under the action of a metal catalyst.

[0023] Compared to conventional quinoxaline synthesis methods, the novelty of the present method lies in the elimination of the need to directly use expensive and non-renewable functionalized petroleum-based platform compounds (such as 1,2-dicarbonyl, α-bromoketone, and α-ketoester) as starting materials. Instead, it directly uses renewable, inexpensive, and readily available sugars as starting materials. Through a series of hierarchical reactions with 1,2-aromatic diamines, 1,2,3,4-tetrahydroquinoxaline derivatives or similar semi-hydrogenated nitrogen-containing aromatic heterocyclic compounds are synthesized in one step. Furthermore, the heterogeneous metal hydrogenation catalyst used in the reaction can be recovered by simple filtration and recycled. Furthermore, the use of environmentally friendly water as the reaction solvent demonstrates the green economy of the reaction. The addition of a certain amount of inorganic base to the reaction system helps promote the conversion of sugars into methylglyoxal intermediates, thereby increasing the yield of 2-methyl-1,2,3,4-tetrahydroquinoxaline products. Therefore, the present invention effectively addresses the problems of traditional synthesis methods, such as the difficulty in obtaining raw materials, harsh reaction conditions, lengthy steps, high costs, and potential environmental pollution.

[0024] Compared with the prior art, the present invention has the following beneficial effects:

[0025] 1. This invention innovatively utilizes renewable, abundant, inexpensive, and readily available sugars as the reaction raw material, avoiding the use of non-renewable and expensive petroleum-based platform compounds (such as 1,2-dicarbonyl, α-bromoketone, and α-ketoester). The reaction utilizes environmentally friendly water as the solvent and a recyclable heterogeneous metal catalyst, making the reaction method environmentally friendly and cost-effective.

[0026] 2. The present invention uses a recyclable heterogeneous metal catalyst to directly synthesize high-value 1,2,3,4-tetrahydroquinoxaline derivatives or similar semi-hydrogenated nitrogen-containing aromatic heterocyclic compounds from sugar in a one-step method under relatively mild conditions (100-220°C). The process is simple, the reaction steps are simple, the reaction equipment is simple, the operation is easy, and the reaction conditions are relatively mild.

[0027] 3. This invention has broad applicability and provides a simple, rapid, effective, and green method for constructing bio-based 1,2,3,4-tetrahydroquinoxaline and its related heterocyclic compounds. Specifically, when using a catalyst encapsulated with metal within molecular sieve crystals, the overall yield of 1,2,3,4-tetrahydroquinoxaline can reach 84% and the yield of individual quinoxaline products can reach 79%. Compared with existing technologies, the high reaction efficiency and recyclable metal catalyst offer significant advantages, making this method suitable for industrial production and promising for broad application. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 2-methyl-1,2,3,4-tetrahydroquinoxaline 1 H NMR spectrum. DETAILED DESCRIPTION

[0029] First of all, it should be noted that the metal catalyst used in the present invention is a heterogeneous catalyst, which is based on molecular sieve, metal oxide or activated carbon as a carrier and elemental metal as an active center; its carrier is selected from Beta molecular sieve, MOR molecular sieve, ZSM-5 molecular sieve, cerium dioxide (CeO2), titanium dioxide (TiO2), aluminum oxide (Al2O3), zirconium dioxide (ZrO2), silicon dioxide (SiO2) or activated carbon, and the metal is selected from any one of Pt, Pd, Rh, Ir, and Ni. The heterogeneous catalyst can be prepared by known techniques, such as optionally by impregnation (or other means) to obtain the surface of molecular sieve, metal oxide or activated carbon carrier. Alternatively, the elemental metal is encapsulated in the molecular sieve crystal by in-situ metal encapsulation. Alternatively, it can be directly purchased from commercial sources.

[0030] The following uses the oxide ZrO2 as a carrier as an example to illustrate the preparation method of the catalyst as follows:

[0031] (1) Prepared by general impregnation method:

[0032] A soluble nitrate, chloride, or sulfate of the catalyst metal is added to a ZrO2 dispersion containing water as the solvent. The mixture is stirred at 25-60°C for at least 10-24 hours, and the solvent is removed by vacuum distillation using a rotary evaporator. The mixture is then dried in an oven at 25-120°C for 4-24 hours. The resulting catalyst precursor is then reduced in a hydrogen atmosphere at 300-500°C to convert the metal ions contained in the catalyst into elemental metal, with a metal content of 0.5-3 wt%.

[0033] (2) Preparation by impregnation method assisted by auxiliary agents:

[0034] A soluble nitrate, chloride, or sulfate of the catalyst metal is mixed with an optional auxiliary agent (such as urea) in distilled water to obtain a metal ion solution. The metal ion solution and a ZrO2 dispersion (the solvent of the dispersion is water) are added to a sealed pressure-resistant container and stirred at 60-100°C for 2-8 hours. The mixture is filtered to obtain a solid residue, which is washed with distilled water and collected as a solid catalyst precursor. After drying in an oven at 25-120°C for 4-24 hours, the solid catalyst precursor is reduced in a hydrogen atmosphere at 300-500°C to convert the metal ions contained in the catalyst into elemental metal with a metal content of 0.5-3wt%.

[0035] (3) Prepared by in-situ encapsulation of metals inside zeolite molecular sieve crystals:

[0036] The preparation of metal-encapsulated zeolite crystals is carried out via a two-step process. For the synthesis of Pt@Beta, a typical preparation involves mixing commercial Beta zeolite with an appropriate amount of 0.02-0.2 M H2PtCl6 aqueous solution. The mixture is sonicated at room temperature for 1 hour and then allowed to stand overnight at room temperature. The resulting mixture is dried at 80°C for 4 hours, calcined at 300-500°C in air for 4 hours, and reduced at 300-500°C in a 10% H2 / Ar atmosphere for 2 hours to obtain Pt / Beta seeds containing 1.0-2.0 wt%. Separately, an aluminosilicate gel was prepared using a Na2O:Al2O3:SiO2:H2O molar ratio of 11:1:26:270 from 0.64 g NaAlO2, 1.12 g NaOH, 4.0 g SiO2, and 13.6 g water. After stirring for 12 hours, 0.4 g of Pt / Beta zeolite seeds were added to the gel and hydrothermally crystallized at 120°C for 3 days. After filtration, washing, and drying, the Pt@Beta product was obtained, with a metal loading of 0.2-0.8 wt%.

[0037] Of course, the above preparation method is only an example, and other methods can also be used to prepare the metal catalyst, and the present invention is not limited thereto.

[0038] The present invention will be further described below with reference to specific embodiments to facilitate understanding of the present invention. However, this does not limit the scope of the present invention, which is subject to the scope of the claims. Engineers skilled in the art may make non-essential improvements and adjustments to the present invention based on the above-described disclosure.

[0039] In each example, the unit of measurement of the metal loading is mass percentage (wt %).

[0040] Example 1: Synthesis of 1,2,3,4-tetrahydroquinoxaline (1a-c)

[0041]

[0042] Glucose (90 mg, 0.5 mmol), o-phenylenediamine (216 mg, 2 mmol), 0.5% Pt / Beta catalyst (56 mg, 1.4 μmol), and water (20 mL) were added to an autoclave in the following order. The molar concentrations of the raw materials added were: glucose (0.025 mol / L), o-phenylenediamine (0.1 mol / L), and metal Pt catalyst (0.28 mol%). The mixture was heated to 220°C under a hydrogen atmosphere (5 MPa) and stirred for 3 h. After completion of the reaction, ethyl acetate was added for extraction. The organic phase was collected and the solvent removed under reduced pressure to obtain a crude product. The crude product was further separated and purified by silica gel column chromatography to obtain pure 1,2,3,4-tetrahydroquinoxaline (1a) as a dark brown oily liquid with a product yield of 13.5 C%. Pure 2-methyl-1,2,3,4-tetrahydroquinoxaline (1b) was obtained as a dark brown oily liquid with a product yield of 27.1 C%. Pure 2,3-dimethyl-1,2,3,4-tetrahydroquinoxaline (1c) was obtained as a dark brown oily liquid with a product yield of 3.3 C%.

[0043] Example 2: Synthesis of 1,2,3,4-tetrahydroquinoxaline (1a-c)

[0044]

[0045] Sucrose (68.5 mg, 0.25 mmol), o-phenylenediamine (216 mg, 2 mmol), 3.0% Pt / ZSM-5 catalyst (16.3 mg, 2.5 μmol), and water (20 mL) were added to an autoclave in the following order. The molar concentrations of the raw materials added were: sucrose (0.0125 mol / L), o-phenylenediamine (0.1 mol / L), and metal Pt catalyst (1.0 mol%). The reaction was heated to 190°C under a hydrogen atmosphere (2 MPa) with stirring for 7 h. After completion of the reaction, ethyl acetate was added for extraction, the organic phase was collected, and the solvent was removed under reduced pressure to obtain a crude product. The crude product was further separated and purified by silica gel column chromatography to obtain pure 1,2,3,4-tetrahydroquinoxaline (1a) as a dark brown oily liquid with a product yield of 12.2 C%. Pure 2-methyl-1,2,3,4-tetrahydroquinoxaline (1b) was obtained as a dark brown oily liquid with a product yield of 32.3 C%. Pure 2,3-dimethyl-1,2,3,4-tetrahydroquinoxaline (1c) was obtained as a dark brown oily liquid with a product yield of 4.5 C%.

[0046] Example 3: Synthesis of 1,2,3,4-tetrahydroquinoxaline (1a-c)

[0047]

[0048] Glyceraldehyde (180 mg, 2 mmol), o-phenylenediamine (216 mg, 2 mmol), 1.0% Pt / MOR catalyst (39 mg, 2 μmol), and water (20 mL) were added to an autoclave in the following order. The molar concentrations of the raw materials added were: glyceraldehyde (0.1 mol / L), o-phenylenediamine (0.1 mol / L), and metal Pt catalyst (0.1 mol%). The mixture was heated to 100°C under a hydrogen atmosphere (1 MPa) and stirred for 24 hours. After completion of the reaction, ethyl acetate was added for extraction. The organic phase was collected and the solvent removed under reduced pressure to obtain a crude product. The crude product was further separated and purified by silica gel column chromatography to obtain pure 1,2,3,4-tetrahydroquinoxaline (1a) as a dark brown oily liquid with a product yield of 1.5 C%; pure 2-methyl-1,2,3,4-tetrahydroquinoxaline (1b) as a dark brown oily liquid with a product yield of 71.1 C%; and pure 2,3-dimethyl-1,2,3,4-tetrahydroquinoxaline (1c) as a dark brown oily liquid with a product yield of 1.3 C%.

[0049] Example 4: Synthesis of 1,2,3,4-tetrahydroquinoxaline (1a-c)

[0050]

[0051] Cellobiose (685 mg, 2 mmol), o-phenylenediamine (2.16 g, 20 mmol), 2.0% Pt / SiO2 catalyst (112 mg, 11.5 μmol), and water (20 mL) were added to an autoclave in the following order. The molar concentrations of the raw materials added were: cellobiose (0.1 mol / L), o-phenylenediamine (1.0 mol / L), and metal Pt catalyst (0.58 mol%). The reaction was heated to 190°C under a hydrogen atmosphere (3 MPa) with stirring for 8 h. After completion of the reaction, ethyl acetate was added for extraction, the organic phase was collected, and the solvent was removed under reduced pressure to obtain a crude product. The crude product was further separated and purified by silica gel column chromatography to obtain pure 1,2,3,4-tetrahydroquinoxaline (1a) as a dark brown oily liquid with a product yield of 14.2 C%; pure 2-methyl-1,2,3,4-tetrahydroquinoxaline (1b) as a dark brown oily liquid with a product yield of 40.2 C%; and pure 2,3-dimethyl-1,2,3,4-tetrahydroquinoxaline (1c) as a dark brown oily liquid with a product yield of 5.6 C%.

[0052] Example 5: Synthesis of 1,2,3,4-tetrahydroquinoxaline (1a-c)

[0053]

[0054] Acetone alcohol (18 mg, 0.2 mmol), o-phenylenediamine (43.2 mg, 0.4 mmol), 1.0% Ir / Al2O3 catalyst (26.9 mg, 1.4 μmol), and water (20 mL) were added to an autoclave in the following order. The molar concentrations of the raw materials added were: acetone aldehyde (0.01 mol / L), o-phenylenediamine (0.02 mol / L), and metallic Ir catalyst (0.7 mol%). The mixture was heated to 180°C under a hydrogen atmosphere (3 MPa) and stirred for 7 h. After completion of the reaction, ethyl acetate was added for extraction. The organic phase was collected and the solvent removed under reduced pressure to obtain a crude product. The crude product was further separated and purified by silica gel column chromatography to obtain pure 1,2,3,4-tetrahydroquinoxaline (1a) as a dark brown oily liquid with a product yield of 1.2 C%; pure 2-methyl-1,2,3,4-tetrahydroquinoxaline (1b) as a dark brown oily liquid with a product yield of 71.2 C%; and pure 2,3-dimethyl-1,2,3,4-tetrahydroquinoxaline (1c) as a dark brown oily liquid with a product yield of 1.1 C%.

[0055] Example 6: Synthesis of 1,2,3,4-tetrahydroquinoxaline (1a-c)

[0056]

[0057] Fructose (90 mg, 0.5 mmol), o-phenylenediamine (216 mg, 2 mmol), 1.0% Pd / TiO2 catalyst (14.9 mg, 1.4 μmol), and water (20 mL) were added to an autoclave in the following order. The molar concentrations of the raw materials added were: fructose (0.025 mol / L), o-phenylenediamine (0.1 mol / L), and metal Pd catalyst (0.28 mol%). The mixture was heated to 180°C under a hydrogen atmosphere (3 MPa) and stirred for 7 h. After completion of the reaction, ethyl acetate was added for extraction. The organic phase was collected and the solvent removed under reduced pressure to obtain a crude product. The crude product was further separated and purified by silica gel column chromatography to obtain pure 1,2,3,4-tetrahydroquinoxaline (1a) as a dark brown oily liquid with a product yield of 12.8 C%; pure 2-methyl-1,2,3,4-tetrahydroquinoxaline (1b) as a dark brown oily liquid with a product yield of 30.2 C%; and pure 2,3-dimethyl-1,2,3,4-tetrahydroquinoxaline (1c) as a dark brown oily liquid with a product yield of 3.8 C%.

[0058] Example 7: Synthesis of 1,2,3,4-tetrahydroquinoxaline (1a-c)

[0059]

[0060] Galactose (90 mg, 0.5 mmol), o-phenylenediamine (216 mg, 2 mmol), 1.0% Rh / CeO2 catalyst (14.4 mg, 1.4 μmol), and water (20 mL) were added to an autoclave in the following order. The molar concentrations of the raw materials added were: galactose (0.025 mol / L), o-phenylenediamine (0.1 mol / L), and metal Rh catalyst (0.28 mol%). The mixture was heated to 180°C under a hydrogen atmosphere (3 MPa) and stirred for 7 h. After completion of the reaction, ethyl acetate was added for extraction, the organic phase was collected, and the solvent was removed under reduced pressure to obtain a crude product. The crude product was further separated and purified by silica gel column chromatography to obtain pure 1,2,3,4-tetrahydroquinoxaline (1a) as a dark brown oily liquid with a product yield of 12.2 C%; pure 2-methyl-1,2,3,4-tetrahydroquinoxaline (1b) as a dark brown oily liquid with a product yield of 31.7 C%; and pure 2,3-dimethyl-1,2,3,4-tetrahydroquinoxaline (1c) as a dark brown oily liquid with a product yield of 3.1 C%.

[0061] Example 8: Synthesis of 1,2,3,4-tetrahydroquinoxaline (1a-c)

[0062]

[0063] Sorbitol (90 mg, 0.5 mmol), o-phenylenediamine (216 mg, 2 mmol), 0.5% Ni / ZrO2 catalyst (16.4 mg, 1.4 μmol), and water (20 mL) were added to an autoclave in the following order. The molar concentrations of the raw materials added were: sorbitol (0.025 mol / L), o-phenylenediamine (0.1 mol / L), and Ni catalyst (0.28 mol%). The mixture was heated to 180°C under a hydrogen atmosphere (3 MPa) and stirred for 7 h. After completion of the reaction, ethyl acetate was added for extraction. The organic phase was collected and the solvent removed under reduced pressure to obtain a crude product. The crude product was further separated and purified by silica gel column chromatography to obtain pure 1,2,3,4-tetrahydroquinoxaline (1a) as a dark brown oily liquid with a product yield of 13.1 C%. Pure 2-methyl-1,2,3,4-tetrahydroquinoxaline (1b) was obtained as a dark brown oily liquid with a product yield of 29.2 C%. Pure 2,3-dimethyl-1,2,3,4-tetrahydroquinoxaline (1c) was obtained as a dark brown oily liquid with a product yield of 2.5 C%.

[0064] Example 9: Synthesis of 1,2,3,4-tetrahydroquinoxaline (1a-c)

[0065]

[0066] Tagatose (90 mg, 0.5 mmol), o-phenylenediamine (216 mg, 2 mmol), 2.0% Pt / C catalyst (27.3 mg, 2.8 μmol), and water (20 mL) were added to an autoclave in the following order. The molar concentrations of the raw materials added were: tagatose (0.025 mol / L), o-phenylenediamine (0.1 mol / L), and metal Pt catalyst (0.56 mol%). The mixture was heated to 180°C under a hydrogen atmosphere (3 MPa) and stirred for 7 h. After completion of the reaction, ethyl acetate was added for extraction. The organic phase was collected and the solvent removed under reduced pressure to obtain a crude product. The crude product was further separated and purified by silica gel column chromatography to obtain pure 1,2,3,4-tetrahydroquinoxaline (1a) as a dark brown oily liquid with a product yield of 14.1 C%; pure 2-methyl-1,2,3,4-tetrahydroquinoxaline (1b) as a dark brown oily liquid with a product yield of 34.2 C%; and pure 2,3-dimethyl-1,2,3,4-tetrahydroquinoxaline (1c) as a dark brown oily liquid with a product yield of 3.5 C%.

[0067] Example 10: Synthesis of 1,2,3,4-tetrahydroquinoxaline (1a-c)

[0068]

[0069] Tagatose (90 mg, 0.5 mmol), o-phenylenediamine (216 mg, 2 mmol), 2.0% Ir / Beta catalyst (26.9 mg, 2.8 μmol), and water (20 mL) were added to an autoclave in the following order. The molar concentrations of the raw materials added were: tagatose (0.025 mol / L), o-phenylenediamine (0.1 mol / L), and metal Ir catalyst (0.56 mol%). The mixture was heated to 180°C under a hydrogen atmosphere (3 MPa) and stirred for 7 h. After completion of the reaction, ethyl acetate was added for extraction. The organic phase was collected and the solvent removed under reduced pressure to obtain a crude product. The crude product was further separated and purified by silica gel column chromatography to obtain pure 1,2,3,4-tetrahydroquinoxaline (1a) as a dark brown oily liquid with a product yield of 14.2 C%; pure 2-methyl-1,2,3,4-tetrahydroquinoxaline (1b) as a dark brown oily liquid with a product yield of 34.0 C%; and pure 2,3-dimethyl-1,2,3,4-tetrahydroquinoxaline (1c) as a dark brown oily liquid with a product yield of 3.4 C%.

[0070] Example 11: Synthesis of 1,2,3,4-tetrahydroquinoxaline (1a-c)

[0071]

[0072] In a high-pressure reactor, mannose (90 mg, 0.5 mmol), o-phenylenediamine (216 mg, 2 mmol), 0.2% Pt@Beta catalyst (136.5 mg, 1.4 pmol), water (20 mL) were added in sequence. The molar concentrations of each raw material added were: mannose (0.025 mol / L), o-phenylenediamine (0.1 mol / L), metal Pt catalyst (0.28 mol%). The reaction was carried out under stirring at 180°C for 7 h in a hydrogen atmosphere (3 MPa). After the reaction was completed, ethyl acetate was added for extraction, the organic phase layer was collected, and the solvent was removed under reduced pressure to obtain a crude product. The obtained crude product was further separated and purified by silica gel column chromatography to obtain pure 1,2,3,4-tetrahydroquinoxaline (1a) as a dark brown oily liquid, with a product yield of 19.4C%; pure 2-methyl-1,2,3,4-tetrahydroquinoxaline (1b) as a dark brown oily liquid, with a product yield of 52.8C%; and pure 2,3-dimethyl-1,2,3,4-tetrahydroquinoxaline (1c) as a dark brown oily liquid, with a product yield of 5.1C%.

[0073] Example 12: Synthesis of 1,2,3,4-tetrahydroquinoxaline (1a-c)

[0074]

[0075] In a high-pressure reactor, mannose (90 mg, 0.5 mmol), o-phenylenediamine (216 mg, 2 mmol), 0.2% Pt@Beta catalyst (136.5 mg, 1.4 pmol), water (20 mL) were added in sequence. The molar concentrations of each raw material added were: mannose (0.025 mol / L), o-phenylenediamine (0.1 mol / L), metal Pt catalyst (0.28 mol%). The reaction was carried out under stirring at 180°C for 7 h in a hydrogen atmosphere (3 MPa). After the reaction was completed, ethyl acetate was added for extraction, the organic phase layer was collected, and the solvent was removed under reduced pressure to obtain a crude product. The obtained crude product was further separated and purified by silica gel column chromatography to obtain pure 1,2,3,4-tetrahydroquinoxaline (1a) as a dark brown oily liquid, with a product yield of 19.4C%; pure 2-methyl-1,2,3,4-tetrahydroquinoxaline (1b) as a dark brown oily liquid, with a product yield of 52.8C%; and pure 2,3-dimethyl-1,2,3,4-tetrahydroquinoxaline (1c) as a dark brown oily liquid, with a product yield of 5.1C%.

[0076] Example 13: Synthesis of 1,2,3,4-tetrahydroquinoxaline (1a-c)

[0077]

[0078] Maltose (85.6 mg, 0.25 mmol), o-phenylenediamine (216 mg, 2 mmol), 0.4% Pt@Beta catalyst (68.3 mg, 1.4 μmol), and water (20 mL) were added to an autoclave in the following order. The molar concentrations of the raw materials added were: maltose (0.0125 mol / L), o-phenylenediamine (0.1 mol / L), and metal Pt catalyst (0.56 mol%). The mixture was heated to 180°C under a hydrogen atmosphere (3 MPa) and stirred for 7 h. After completion of the reaction, ethyl acetate was added for extraction. The organic phase was collected and the solvent removed under reduced pressure to obtain a crude product. The crude product was further separated and purified by silica gel column chromatography to obtain pure 1,2,3,4-tetrahydroquinoxaline (1a) as a dark brown oily liquid with a product yield of 18.1 C%; pure 2-methyl-1,2,3,4-tetrahydroquinoxaline (1b) as a dark brown oily liquid with a product yield of 50.2 C%; and pure 2,3-dimethyl-1,2,3,4-tetrahydroquinoxaline (1c) as a dark brown oily liquid with a product yield of 4.5 C%.

[0079] Example 14: Synthesis of 1,2,3,4-tetrahydroquinoxaline (1a-c)

[0080]

[0081] Erythrose (60 mg, 0.5 mmol), o-phenylenediamine (216 mg, 2 mmol), 0.4% Pd@MOR catalyst (37.2 mg, 1.4 μmol), and water (20 mL) were added to an autoclave in the following order. The molar concentrations of the raw materials added were: erythrose (0.025 mol / L), o-phenylenediamine (0.1 mol / L), and metal Pd catalyst (0.28 mol%). The reaction was heated to 180°C under a hydrogen atmosphere (3 MPa) with stirring for 7 h. After completion of the reaction, ethyl acetate was added for extraction. The organic phase was collected and the solvent removed under reduced pressure to obtain a crude product. The crude product was further separated and purified by silica gel column chromatography to obtain pure 1,2,3,4-tetrahydroquinoxaline (1a) as a dark brown oily liquid with a product yield of 4.1 C%; pure 2-methyl-1,2,3,4-tetrahydroquinoxaline (1b) as a dark brown oily liquid with a product yield of 25.2 C%; and pure 2,3-dimethyl-1,2,3,4-tetrahydroquinoxaline (1c) as a dark brown oily liquid with a product yield of 7.6 C%.

[0082] Example 15: Synthesis of 1,2,3,4-tetrahydroquinoxaline (1a-c)

[0083]

[0084] Sucrose (85.6 mg, 0.25 mmol), o-phenylenediamine (216 mg, 2 mmol), 0.4% Rh@ZSM-5 catalyst (36 mg, 1.4 μmol), and water (20 mL) were added to an autoclave in the following order. The molar concentrations of the raw materials added were: sucrose (0.0125 mol / L), o-phenylenediamine (0.1 mol / L), and metal Rh catalyst (0.56 mol%). The mixture was heated to 180°C under a hydrogen atmosphere (3 MPa) and stirred for 7 h. After completion of the reaction, ethyl acetate was added for extraction. The organic phase was collected and the solvent removed under reduced pressure to obtain a crude product. The crude product was further separated and purified by silica gel column chromatography to obtain pure 1,2,3,4-tetrahydroquinoxaline (1a) as a dark brown oily liquid with a product yield of 13.1 C%; pure 2-methyl-1,2,3,4-tetrahydroquinoxaline (1b) as a dark brown oily liquid with a product yield of 38.2 C%; and pure 2,3-dimethyl-1,2,3,4-tetrahydroquinoxaline (1c) as a dark brown oily liquid with a product yield of 3.8 C%.

[0085] Example 16: Synthesis of 1,2,3,4-tetrahydroquinoxaline (1a-c)

[0086]

[0087] Glucose (90 mg, 0.5 mmol), o-phenylenediamine (216 mg, 2 mmol), 0.4% Ni@Beta catalyst (20.5 mg, 1.4 μmol), and water (20 mL) were added to an autoclave in the following order. The molar concentrations of the raw materials added were: glucose (0.025 mol / L), o-phenylenediamine (0.1 mol / L), and metal Ni catalyst (0.28 mol%). The mixture was heated to 180°C under a hydrogen atmosphere (3 MPa) and stirred for 7 h. After completion of the reaction, ethyl acetate was added for extraction. The organic phase was collected and the solvent removed under reduced pressure to obtain a crude product. The crude product was further separated and purified by silica gel column chromatography to obtain pure 1,2,3,4-tetrahydroquinoxaline (1a) as a dark brown oily liquid with a product yield of 11.3 C%. Pure 2-methyl-1,2,3,4-tetrahydroquinoxaline (1b) was obtained as a dark brown oily liquid with a product yield of 30.1 C%. Pure 2,3-dimethyl-1,2,3,4-tetrahydroquinoxaline (1c) was obtained as a dark brown oily liquid with a product yield of 3.2 C%.

[0088] Example 17: Synthesis of 2-methyl-1,2,3,4-tetrahydroquinoxaline (1b)

[0089]

[0090] Glucose (90 mg, 0.5 mmol), o-phenylenediamine (216 mg, 2 mmol), 0.4% Pt@Beta catalyst (68.3 mg, 1.4 μmol), potassium carbonate (18 mg, 0.13 mmol), and water (20 mL) were added to an autoclave in the following order. The molar concentrations of the raw materials added were: glucose (0.025 mol / L), o-phenylenediamine (0.1 mol / L), potassium carbonate (6.5 mmol / L), and metal Pt catalyst (0.28 mol%). The mixture was heated to 180°C under a hydrogen atmosphere (2 MPa) and stirred for 7 h. After the reaction, ethyl acetate was added for extraction. The organic phase was collected and the solvent was removed under reduced pressure to obtain a crude product. The crude product was further separated and purified by silica gel column chromatography to obtain pure 2-methyl-1,2,3,4-tetrahydroquinoxaline (1b) as a dark brown oily liquid with a product yield of 76.6 C%.

[0091] Example 18: Synthesis of 2-methyl-1,2,3,4-tetrahydroquinoxaline (1b)

[0092]

[0093] Glucose (90 mg, 0.5 mmol), o-phenylenediamine (216 mg, 2 mmol), 0.4% Ir@Beta catalyst (67.2 mg, 1.4 μmol), potassium carbonate (36 mg, 0.26 mmol), and water (20 mL) were added to an autoclave in the following order. The molar concentrations of the raw materials added were: glucose (0.025 mol / L), o-phenylenediamine (0.1 mol / L), potassium carbonate (13 mmol / L), and metal Ir catalyst (0.28 mol%). The mixture was heated to 180°C under a hydrogen atmosphere (2 MPa) and stirred for 7 h. After the reaction, ethyl acetate was added for extraction. The organic phase was collected and the solvent was removed under reduced pressure to obtain a crude product. The crude product was further separated and purified by silica gel column chromatography to obtain pure 2-methyl-1,2,3,4-tetrahydroquinoxaline (1b) as a dark brown oily liquid with a product yield of 75.7 C%.

[0094] Example 19: Synthesis of 2-methyl-1,2,3,4-tetrahydroquinoxaline (1b)

[0095]

[0096] Glucose (90 mg, 0.5 mmol), o-phenylenediamine (216 mg, 2 mmol), 0.4% Rh@Beta catalyst (36 mg, 1.4 μmol), sodium carbonate (13.8 mg, 0.13 mmol), and water (20 mL) were added to an autoclave in the following order. The molar concentrations of the raw materials added were: glucose (0.025 mol / L), o-phenylenediamine (0.1 mol / L), sodium carbonate (6.5 mmol / L), and metal Rh catalyst (0.28 mol%). The mixture was heated to 180°C under a hydrogen atmosphere (2 MPa) and stirred for 7 h. After the reaction, ethyl acetate was added for extraction. The organic phase was collected and the solvent was removed under reduced pressure to obtain a crude product. The crude product was further separated and purified by silica gel column chromatography to obtain pure 2-methyl-1,2,3,4-tetrahydroquinoxaline (1b) as a dark brown oily liquid with a yield of 70.2 C%.

[0097] Example 20: Synthesis of 2-methyl-1,2,3,4-tetrahydroquinoxaline (1b)

[0098]

[0099] Glucose (90 mg, 0.5 mmol), o-phenylenediamine (216 mg, 2 mmol), 0.4% Pt@MOR catalyst (68.3 mg, 1.4 μmol), rubidium carbonate (30 mg, 0.13 mmol), and water (20 mL) were added to an autoclave in the following order. The molar concentrations of the raw materials added were: glucose (0.025 mol / L), o-phenylenediamine (0.1 mol / L), rubidium carbonate (6.5 mmol / L), and metal Pt catalyst (0.28 mol%). The mixture was heated to 180°C under a hydrogen atmosphere (2 MPa) and stirred for 7 h. After the reaction, ethyl acetate was added for extraction. The organic phase was collected and the solvent was removed under reduced pressure to obtain a crude product. The crude product was further separated and purified by silica gel column chromatography to obtain pure 2-methyl-1,2,3,4-tetrahydroquinoxaline (1b) as a dark brown oily liquid with a yield of 72.4 C%.

[0100] Example 21: Synthesis of 2-methyl-1,2,3,4-tetrahydroquinoxaline (1b)

[0101]

[0102] Glucose (90 mg, 0.5 mmol), o-phenylenediamine (216 mg, 2 mmol), 0.4% Ir@MOR catalyst (67.2 mg, 1.4 μmol), cesium carbonate (42.4 mg, 0.13 mmol), and water (20 mL) were added to an autoclave in the following order. The molar concentrations of the raw materials added were: glucose (0.025 mol / L), o-phenylenediamine (0.1 mol / L), cesium carbonate (6.5 mmol / L), and metal Ir catalyst (0.28 mol%). The mixture was heated to 180°C under a hydrogen atmosphere (2 MPa) and stirred for 7 h. After the reaction, ethyl acetate was added for extraction. The organic phase was collected and the solvent was removed under reduced pressure to obtain a crude product. The crude product was further separated and purified by silica gel column chromatography to obtain pure 2-methyl-1,2,3,4-tetrahydroquinoxaline (1b) as a dark brown oily liquid with a product yield of 74.5 C%.

[0103] Example 22: Synthesis of 2,6,7-trimethyl-1,2,3,4-tetrahydroquinoxaline (2)

[0104]

[0105] Glucose (90 mg, 0.5 mmol), 4,5-dimethyl-o-phenylenediamine (272 mg, 2 mmol), 0.4% Pt@Beta catalyst (68.3 mg, 1.4 μmol), potassium carbonate (18 mg, 0.13 mmol), and water (20 mL) were added to a high-pressure reactor in sequence. The molar concentrations of the raw materials added were: glucose (0.025 mol / L), 4,5-dimethyl-o-phenylenediamine (0.1 mol / L), potassium carbonate (6.5 mmol / L), and metal Pt catalyst (0.28 mol%). The mixture was heated to 180°C in a hydrogen atmosphere (2 MPa) and stirred for 7 h. After the reaction was completed, ethyl acetate was added for extraction, the organic phase was collected, and the solvent was removed under reduced pressure to obtain a crude product. The crude product was further separated and purified by silica gel column chromatography to obtain pure 2,6,7-trimethyl-1,2,3,4-tetrahydroquinoxaline (2) as a dark brown oily liquid with a product yield of 74.2 C%.

[0106] Example 23: Synthesis of 6,7-difluoro-2-methyl-1,2,3,4-tetrahydroquinoxaline (3)

[0107]

[0108] Glucose (90 mg, 0.5 mmol), 4,5-difluoro-o-phenylenediamine (288 mg, 2 mmol), 0.4% Rh@MOR catalyst (36 mg, 1.4 μmol), potassium carbonate (18 mg, 0.13 mmol), and water (20 mL) were added to a high-pressure reactor in sequence. The molar concentrations of the raw materials added were: glucose (0.025 mol / L), 4,5-difluoro-o-phenylenediamine (0.1 mol / L), potassium carbonate (6.5 mmol / L), and metal Pt catalyst (0.28 mol%). The mixture was heated to 180°C in a hydrogen atmosphere (2 MPa) and stirred for 7 h. After the reaction was completed, ethyl acetate was added for extraction, the organic phase was collected, and the solvent was removed under reduced pressure to obtain a crude product. The crude product was further separated and purified by silica gel column chromatography to obtain pure 6,7-difluoro-2-methyl-1,2,3,4-tetrahydroquinoxaline (3) as a dark brown oily liquid with a product yield of 76.2 C%.

[0109] Example 24: Synthesis of 6,7-dichloro-2-methyl-1,2,3,4-tetrahydroquinoxaline (4)

[0110]

[0111] Glucose (90 mg, 0.5 mmol), 4,5-dichloro-o-phenylenediamine (354 mg, 2 mmol), 0.4% Pt@Beta catalyst (68.3 mg, 1.4 μmol), potassium carbonate (18 mg, 0.13 mmol), and water (20 mL) were added to a high-pressure reactor in sequence. The molar concentrations of the raw materials added were: glucose (0.025 mol / L), 4,5-dichloro-o-phenylenediamine (0.1 mol / L), potassium carbonate (6.5 mmol / L), and metal Pt catalyst (0.28 mol%). The mixture was heated to 180°C in a hydrogen atmosphere (2 MPa) and stirred for 7 h. After the reaction was completed, ethyl acetate was added for extraction, the organic phase was collected, and the solvent was removed under reduced pressure to obtain a crude product. The crude product was further separated and purified by silica gel column chromatography to obtain pure 6,7-dichloro-2-methyl-1,2,3,4-tetrahydroquinoxaline (4) as a dark brown oily liquid with a product yield of 67.3 C%.

[0112] Example 25: Synthesis of 2-methyl-1,2,3,4-tetrahydrobenzo[g]quinoxaline (5)

[0113]

[0114] Glucose (90 mg, 0.5 mmol), 2,3-naphthalenediamine (316 mg, 2 mmol), 0.4% Pt@Beta catalyst (68.3 mg, 1.4 μmol), potassium carbonate (18 mg, 0.13 mmol), and water (20 mL) were added to an autoclave in sequence. The molar concentrations of the raw materials added were: glucose (0.025 mol / L), 2,3-naphthalenediamine (0.1 mol / L), potassium carbonate (6.5 mmol / L), and metal Pt catalyst (0.28 mol%). The mixture was heated to 180°C in a hydrogen atmosphere (2 MPa) and stirred for 7 h. After the reaction was completed, ethyl acetate was added for extraction, the organic phase was collected, and the solvent was removed under reduced pressure to obtain a crude product. The crude product was further separated and purified by silica gel column chromatography to obtain pure 2-methyl-1,2,3,4-tetrahydrobenzo[g]quinoxaline (5) as a dark brown oily liquid with a product yield of 62.1 C%.

[0115] Example 26: Synthesis of 1,2,3,4-tetrahydroquinoxaline isomer compound (6)

[0116]

[0117] Glucose (90 mg, 0.5 mmol), 4-methyl-o-phenylenediamine (244 mg, 2 mmol), 0.4% Pt@Beta catalyst (68.3 mg, 1.4 μmol), potassium carbonate (18 mg, 0.13 mmol), and water (20 mL) were added to an autoclave in the following order. The molar concentrations of the raw materials added were: glucose (0.025 mol / L), 4-methyl-o-phenylenediamine (0.1 mol / L), potassium carbonate (6.5 mmol / L), and Pt catalyst (0.28 mol%). The mixture was heated to 180°C under a hydrogen atmosphere (2 MPa) and stirred for 7 h. After completion of the reaction, ethyl acetate was added for extraction. The organic phase was collected and the solvent removed under reduced pressure to obtain a crude product. The crude product was further separated and purified by silica gel column chromatography to obtain pure product (6) with a yield of 74.2 C%, which was a dark brown oily liquid, including isomers 6a (2,7-dimethyl-1,2,3,4-tetrahydroquinoxaline) and 6b (2,6-dimethyl-1,2,3,4-tetrahydroquinoxaline).

[0118] Example 27: Synthesis of 1,2,3,4-tetrahydroquinoxaline isomer compound (7)

[0119]

[0120] Glucose (90 mg, 0.5 mmol), 4-methoxy-o-phenylenediamine (276 mg, 2 mmol), 0.4% Pt@Beta catalyst (68.3 mg, 1.4 μmol), potassium carbonate (18 mg, 0.13 mmol), and water (20 mL) were added to an autoclave in the following order. The molar concentrations of the raw materials added were: glucose (0.025 mol / L), 4-methoxy-o-phenylenediamine (0.1 mol / L), potassium carbonate (6.5 mmol / L), and Pt catalyst (0.28 mol%). The mixture was heated to 180°C under a hydrogen atmosphere (2 MPa) and stirred for 7 h. After completion of the reaction, ethyl acetate was added for extraction. The organic phase was collected and the solvent removed under reduced pressure to obtain a crude product. The crude product was further separated and purified by silica gel column chromatography to obtain pure product (7) with a yield of 76.3 C%, which was a dark brown oily liquid, including isomers 7a (7-methoxy-2-methyl-1,2,3,4-tetrahydroquinoxaline) and 7b (6-methoxy-2-methyl-1,2,3,4-tetrahydroquinoxaline).

[0121] Example 28: Synthesis of 1,2,3,4-tetrahydroquinoxaline isomer compound (8)

[0122]

[0123] Glucose (90 mg, 0.5 mmol), 4-fluoro-o-phenylenediamine (252 mg, 2 mmol), 0.4% Pt@Beta catalyst (68.3 mg, 1.4 μmol), potassium carbonate (18 mg, 0.13 mmol), and water (20 mL) were added to an autoclave in the following order. The molar concentrations of the raw materials added were: glucose (0.025 mol / L), 4-fluoro-o-phenylenediamine (0.1 mol / L), potassium carbonate (6.5 mmol / L), and Pt catalyst (0.28 mol%). The mixture was heated to 180°C under a hydrogen atmosphere (2 MPa) and stirred for 7 h. After completion of the reaction, ethyl acetate was added for extraction. The organic phase was collected and the solvent removed under reduced pressure to obtain a crude product. The crude product was further separated and purified by silica gel column chromatography to obtain pure product (8) with a yield of 70.3% as a dark brown oily liquid, including isomers 8a (7-fluoro-2-methyl-1,2,3,4-tetrahydroquinoxaline) and 8b (6-fluoro-2-methyl-1,2,3,4-tetrahydroquinoxaline).

[0124] Example 29: Synthesis of 1,2,3,4-tetrahydroquinoxaline isomer compound (9)

[0125]

[0126] Glucose (90 mg, 0.5 mmol), 4-chloro-o-phenylenediamine (285 mg, 2 mmol), 0.4% Pt@Beta catalyst (68.3 mg, 1.4 μmol), potassium carbonate (18 mg, 0.13 mmol), and water (20 mL) were added to an autoclave in the following order. The molar concentrations of the raw materials added were: glucose (0.025 mol / L), 4-chloro-o-phenylenediamine (0.1 mol / L), potassium carbonate (6.5 mmol / L), and Pt catalyst (0.28 mol%). The mixture was heated to 180°C under a hydrogen atmosphere (2 MPa) and stirred for 7 h. After completion of the reaction, ethyl acetate was added for extraction. The organic phase was collected and the solvent removed under reduced pressure to obtain a crude product. The crude product was further separated and purified by silica gel column chromatography to obtain pure product (9) with a yield of 70.3% as a dark brown oily liquid, including isomers 9a (7-chloro-2-methyl-1,2,3,4-tetrahydroquinoxaline) and 9b (6-chloro-2-methyl-1,2,3,4-tetrahydroquinoxaline).

[0127] Example 30: Synthesis of Semi-Hydrogenated Nitrogen-Containing Aromatic Heterocyclic Isomer Compound (10)

[0128]

[0129] Glucose (90 mg, 0.5 mmol), 2,3-diaminopyridine (218 mg, 2 mmol), 0.4% Pt@Beta catalyst (68.3 mg, 1.4 μmol), potassium carbonate (18 mg, 0.13 mmol), and water (20 mL) were added to an autoclave in the following order. The molar concentrations of the raw materials added were: glucose (0.025 mol / L), 2,3-diaminopyridine (0.1 mol / L), potassium carbonate (6.5 mmol / L), and Pt catalyst (0.28 mol%). The mixture was heated to 180°C under a hydrogen atmosphere (2 MPa) and stirred for 7 h. After completion of the reaction, ethyl acetate was added for extraction. The organic phase was collected and the solvent removed under reduced pressure to obtain the crude product. The crude product was further separated and purified by silica gel column chromatography to obtain pure product (10) with a yield of 67.2 C%, which was a black oily liquid and included isomers 10a (2-methyl-1,2,3,4-tetrahydropyridine [2,3-b] pyrazine) and 10b (3-methyl-1,2,3,4-tetrahydropyridine [2,3-b] pyrazine).

[0130] In the above examples, the products obtained after separation and purification mainly include 1,2,3,4-tetrahydroquinoxaline derivatives. Of course, some of the products in the examples are other semi-hydrogenated nitrogen-containing aromatic heterocyclic products that are not 1,2,3,4-tetrahydroquinoxaline derivatives; for example, the product "2-methyl-1,2,3,4-tetrahydrobenzo[g]quinoxaline (5)" in Example 25, and the product (10) in Example 30.

Claims

1. A method for directly preparing a semi-hydrogenated nitrogen-containing aromatic heterocyclic compound from sugar, characterized in that: The semi-hydrogenated nitrogen-containing aromatic heterocyclic compound is prepared by the following reaction using sugar and 1,2-aromatic diamine as starting materials, water as solvent, and in the presence of metal catalyst and hydrogen: ； In the above formula: Ring A in 1,2-aromatic diamine is phenyl, naphthyl or pyridyl, R 1 is one or more of hydrogen, alkyl, alkoxy, and halogen; in the reaction product, R 2 、R 3 are the same or different substituent groups selected from hydrogen or methyl; or, an inorganic base is further added to the reaction raw materials to improve the selectivity of the reaction; The metal catalyst is a heterogeneous catalyst, including an elemental metal as a catalyst active center and a zeolite molecular sieve as a carrier, and the elemental metal is encapsulated inside the molecular sieve crystal; in the metal catalyst, the content of the elemental metal is 0.5 to 3 wt%, and the elemental metal is selected from any one of Pt, Pd, Rh, Ir, and Ni.

2. The method according to claim 1, characterized in that The sugar is any one of the following: glucose, sucrose, glyceraldehyde, cellobiose, acetol, fructose, galactose, sorbose, tagatose, mannose, xylose, maltose or erythrose.

3. The method according to claim 1, characterized in that The 1,2-aromatic diamine is any one of the following: o-phenylenediamine, 4,5-dimethyl o-phenylenediamine, 4,5-difluoro o-phenylenediamine, 4,5-dichloro o-phenylenediamine, 2,3-naphthalene diamine, 4-methyl o-phenylenediamine, 4-methoxy o-phenylenediamine, 4-fluoro o-phenylenediamine, 4-chloro o-phenylenediamine or 2,3-diaminopyridine.

4. The method according to claim 1, wherein An inorganic base is further added to the reactants to improve the selectivity of the reaction. The inorganic base is any one of the following: potassium carbonate, sodium carbonate, rubidium carbonate or cesium carbonate.

5. The method according to claim 1, wherein The zeolite molecular sieve is selected from any one of Beta molecular sieve, MOR molecular sieve and ZSM-5 molecular sieve.

6. The method according to any one of claims 1 to 5, characterized in that The method specifically comprises the following steps: (1) Add sugar, 1,2-aromatic diamine, metal catalyst and water to an autoclave, or further add an inorganic base, and then stir evenly; control the amount of raw materials added so that the initial mixture of the reaction system has the following molar concentrations: sugar 0.01 to 0.1 mol / L; 1,2-aromatic diamine 0.02 to 1 mol / L; metal catalyst 0.1 to 1 mol; and inorganic base 0 to 13 mmol / L. (2) Close the autoclave and conduct a hydrothermal reaction in a hydrogen atmosphere at 1-5 MPa; control the reaction temperature to 100-220 °C and the reaction time to 3-24 h under stirring; (3) After the reaction is completed, the organic phase is collected and extracted to obtain a crude product; the crude product is separated and purified to obtain a brown or brown oily liquid, which is a semi-hydrogenated nitrogen-containing aromatic heterocyclic compound.

7. The method according to claim 6, characterized in that In the step (3), the organic phase layer is extracted with an organic solvent, and then the solvent is removed under reduced pressure to obtain a crude product.

8. The method according to claim 6, characterized in that In the step (3), the crude reaction product is separated by silica gel column chromatography to obtain a purified product.

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