Method for synthesizing N-heterocyclic compounds catalyzed by manganese complexes under mild conditions

Abstract

The present invention discloses a method for synthesizing N-heterocyclic compounds using a manganese complex under mild conditions. The method comprises: mixing a tridentate nitrogen ligand manganese complex (I), a base, and a solvent under a nitrogen atmosphere, stirring the mixture uniformly, then adding an amino alcohol (II) and a ketone (III), heating the mixture to 40-100° C. and reacting the mixture for 24-48 hours, and performing post-treatment to obtain a target product, an N-heterocyclic compound (IV). The method has simple operation, mild reaction conditions, a wide range of reaction substrate applications, high selectivity, a stable catalyst, and high efficiency, and has potential application value in the field of synthesis.

Description

Technical Field

[0001] The present invention relates to a method for synthesizing N-heterocyclic compounds, and in particular to a method for synthesizing N-heterocyclic compounds under mild conditions by utilizing a rigid skeleton tridentate nitrogen ligand manganese complex for catalysis. Background Art

[0002] N-heterocyclic compounds are a class of organic compounds with important physiological activities and wide application value. They play an important role in drug synthesis, materials science and other fields.

[0003] Traditional methods for synthesizing N-heterocyclic compounds use nitrogen or ammonia as a nitrogen source, reacting with hydrocarbons in the presence of a catalyst to produce N-heterocyclic compounds, or by reacting aromatic amines with ketones to produce products with ammonia-containing heterocycles. These methods typically operate under high temperature and pressure conditions, resulting in low yields and complex synthesis processes.

[0004] In recent years, the acceptor-free dehydrogenative coupling (ADC) process has attracted considerable attention due to its lack of need for sacrificial hydrogen acceptors and the addition of oxidants. Using inexpensive and readily available alcohols as starting materials, this process boasts high atom economy, significantly improving both economic and environmental performance. Building on this foundation, research on the transition-metal-catalyzed synthesis of N-heterocyclic compounds using alcohols as coupling agents has garnered widespread attention. Furthermore, manganese, the third most abundant metal in the Earth's crust, offers a highly attractive catalyst alternative due to its diverse valence and rich coordination number.

[0005] At present, the research on manganese-catalyzed synthesis of heterocyclic compounds has been widely carried out, and metal manganese precursors represented by Mn(CO)5Br have been widely developed and applied in metal-catalyzed reactions. In 2018, the Maji group reported that a manganese complex generated in situ with a tridentate nitrogen ligand and Mn(CO)5Br was used as a catalyst to prepare quinoline derivatives by reacting amino alcohols and ketones at 140 degrees [Barman, Milan K., Akash Jana, and Biplab Maji. Phosphine-Free NNN-Manganese Complex Catalyzed α-Alkylation of Ketones with Primary Alcohols and Quinoline Synthesis. Advanced Synthesis & Catalysis, 2018, 360(17): 3233-3238.]. In 2021, Xia Haiping's group reported the synthesis of N-heterocyclic compounds catalyzed by monovalent manganese carbonyl complexes with hydroxybipyridine as ligand at 130 degrees [Zhang, Chong, et al. Manganese (I) -Catalyzed Transfer Hydrogenation and Acceptorless Dehydrogenative Condensation: Promotional Influence of the Uncoordinated N-Heterocycle. Organometallics, 2021, 38(16): 3218-3226.]. In 2021, Sun Wenhua's group used NN H Y's monovalent manganese complex was used to synthesize quinoline, and the reaction temperature was 120 degrees [Wang, Zheng, et al. Direct synthesis of ring-fused quinolines and pyridines catalyzed by NN H Y-ligated manganese complexes (Y=NR2 or SR). Catalysis Science & Technology, 2021, 11(24):8026-8036.].

[0006] Mn(CO)5Br has become a hot topic in the study of manganese-catalyzed reactions due to its high reactivity, but carbonyl manganese is relatively expensive and difficult to store stably. Divalent manganese salts such as MnCl2, MnBr2, Mn(OTf)2 are relatively cheap and stable, and have good research and application prospects. There is only one report on the catalytic synthesis of quinoline derivatives using divalent manganese salts as metal precursors. In 2022, the Kundu group reported the catalytic synthesis of N-heterocyclic compounds such as quinoline, pyrrole and pyridine by tridentate nitrogen ligand manganese chloride complexes at 120-150 degrees [Maji, Ankur, et al. Well-Defined Phosphine-Free Manganese(II)-Complex-Catalyzed Synthesis of Quinolines, Pyrroles, and Pyridines. The Journal of Organic Chemistry, 2022, 87(13): 8351-8367.].

[0007] According to the above-reported methods for synthesizing N-heterocyclic compounds, it can be seen that the reaction temperature for the synthesis of N-heterocyclic compounds catalyzed by either Mn(I) or Mn(II) complexes is above 120°C. Therefore, the development of a mild manganese catalytic system is of great significance. Summary of the Invention

[0008] The present invention aims to synthesize N-heterocyclic compounds under mild conditions using a stable manganese complex as a catalyst. The catalytic system of the present invention has mild conditions, a stable catalyst, high efficiency, and simple operation.

[0009] The technical solutions of the present invention are as follows:

[0010] A method for synthesizing N-heterocyclic compounds catalyzed by a manganese complex, comprising:

[0011] Under a nitrogen atmosphere, a tridentate nitrogen ligand manganese complex (I), a base, and a solvent are mixed and stirred uniformly. Then, amino alcohol (II) and ketone (III) are added. The temperature is raised to 40-100°C and the reaction is carried out for 24-48 hours. After post-treatment, the target product N-heterocyclic compound (IV) is obtained.

[0012] in,

[0013] Amino alcohol (II) and ketone (III) are the reaction raw materials, tridentate nitrogen ligand manganese complex (I) is the catalyst, and base is the activator;

[0014] The molar ratio of amino alcohol (II), ketone (III), base, and tridentate nitrogen ligand manganese complex (I) is 1:1.2-1.8:1.0-2.0:0.01-0.05, preferably 1:1.4:1.5:0.03;

[0015] The general formula of base can be written as: M a X b ; wherein M represents Na, K or Li, X represents C(CH3)3O, OH, CO3, CH3O, CH3CH2O or CH3COO, a=1~2, b=1; preferably the base is t-BuOK;

[0016] The solvent is selected from one of toluene, 2-methyltetrahydrofuran, tetrahydrofuran, 1,4-dioxane, acetonitrile, methyl tert-butyl ether, and dichloroethane, preferably toluene;

[0017] The preferred reaction temperature is 50-100°C and the reaction time is 24-48h; the optimal reaction temperature is 70°C and the reaction time is 24h;

[0018] The specific post-treatment method is as follows: after the reaction is completed, the reaction solution is cooled to room temperature, water is added to quench the reaction, the aqueous phase is extracted with toluene, the organic phases are combined, dried over anhydrous sodium sulfate, and then concentrated, the sample is mixed with silica gel and subjected to column chromatography separation, using a mixture of petroleum ether and ethyl acetate in a volume ratio of 100:1 to 50:1 as the eluent, the eluate containing the target product is collected, and evaporated to dryness under reduced pressure to obtain N-heterocyclic compound (IV);

[0019] The structural formula of the tridentate nitrogen ligand manganese complex (I) is as follows:

[0020]

[0021] In formula (I), R is hydrogen, ethyl or isopropyl, preferably ethyl;

[0022] Specific tridentate nitrogen ligand manganese complexes include: Mn-1, Mn-2, Mn-3, and the structural formula is as follows:

[0023]

[0024] The reaction raw materials amino alcohol (II) and ketone (III) and the target product N-heterocyclic compound (IV) have the following structural formula:

[0025]

[0026] In formula (II), formula (III) or formula (IV),

[0027] R 1 is hydrogen, C1-C4 alkyl, halogen, phenyl or substituted phenyl; the phenyl ring of the substituted phenyl is substituted by one or more substituents, each of which is independently selected from C1-C4 alkyl, halogen, C1-C4 alkoxy, trifluoromethyl, amino, nitrile or phenyl;

[0028] R 2 is hydrogen or phenyl;

[0029] R 3 is a C1-C4 alkyl group, a C3-C6 cycloalkyl group, a phenyl group, a substituted phenyl group, or a heteroaryl group; the phenyl ring of the substituted phenyl group is substituted by one or more substituents, each of which is independently selected from a C1-C4 alkyl group, a halogen group, a C1-C4 alkoxy group, a trifluoromethyl group, an amino group, a nitrile group, or a phenyl group; the heteroaryl group is exemplified by a 2-pyridyl group or a 2-thienyl group;

[0030] R 4 It is hydrogen, C1~C4 alkyl or C3~C6 cycloalkyl.

[0031] The beneficial effects of the present invention are:

[0032] This invention utilizes a tridentate nitrogen ligand manganese complex catalyst to effectively catalyze the synthesis of N-heterocyclic compounds under mild conditions. Compared with existing methods, this invention offers simple operation, mild reaction conditions, a wide range of substrate applicability, high selectivity, a stable catalyst, and high efficiency, demonstrating potential application value in the synthesis field. DETAILED DESCRIPTION

[0033] The present invention is further described below by means of specific examples, but the protection scope of the present invention is not limited thereto.

[0034] In the following examples,

[0035] The catalyst uses a manganese complex Mn-1, and its synthesis method is as follows:

[0036] (Raw materials are MnCl2, )

[0037] A 25 mL Schlenk tube was charged with 2-benzimidazolyl-5,6,7,8-tetrahydroquinolin-8-one (263 mg, 1 mmol). The tube was then transferred to a glove box, where anhydrous manganese chloride (119 mg, 0.95 eq.) was added. The tube was removed from the glove box and, under a nitrogen atmosphere, 2,6-diethylaniline (165 μL, 1.0 eq.) and deoxygenated acetic acid (15 mL) were added sequentially. The tube was placed in a 130°C oil bath and stirred for 10 h. The reaction was terminated, at which point a large amount of solid precipitated. After the tube was cooled to room temperature, the reaction solution was centrifuged. Dichloromethane (5 mL) was added to the resulting solid, which was then ultrasonically washed until no ligand remained. This afforded 442 mg of a pale yellow-green powder in an 85% yield.

[0038] 2,6-Diethylaniline (100 mL) was purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.; MnCl2 (25 g) was purchased from Shanghai Bid Pharmaceutical Technology Co., Ltd.; and the synthesis of 2-benzimidazolyl-5,6,7,8-tetrahydroquinolin-8-one was based on the literature reference Yongfeng H., Randi Z., et al., Selectivity Effects on N,N,N′-Cobalt Catalyzed Ethylene Dimerization / Trimerization Dictated through Choice of Aluminoxane Cocatalyst[J]. Organometallics 2019, 38, 5, 1143-1150.

[0039] Example 1: Synthesis of 2-phenylquinoline:

[0040] (Raw materials are )

[0041] A 25 mL sealed tube was charged with the Mn-1 complex (15.6 mg, 3 mol%). The tube was then transferred to a glove box. Inside the glove box, t-BuOK (168 mg, 1.5 eq.) and 2 mL of toluene were added sequentially to the tube. The mixture was stirred and activated for 15 minutes. After 15 minutes, o-aminobenzyl alcohol (123 mg, 1 mmol) and acetophenone (168 mg, 1.4 eq.) were added sequentially to the tube. The tube was sealed and stirred at 70°C for 24 hours. The reaction was terminated and separated by column chromatography to yield 184 mg of a white solid (90% yield). Characterization data for the product are as follows: 1 H NMR(500MHz, CDCl3)δ8.27–8.20(m,1H),8.20–8.11(m,3H),7.86(d,J=8.7Hz ,1H),7.81(m,1H),7.77–7.72(m,1H),7.59–7.52(m,3H),7.52–7.45(m,1H).

[0042] Example 2: Synthesis of 2-(2-methylphenyl)quinoline:

[0043] (Raw materials are )

[0044] A 25 mL sealed tube was added with the Mn-1 complex (15.6 mg, 3 mol%). The 25 mL sealed tube was transferred to a glove box. Inside the glove box, t-BuOK (168 mg, 1.5 eq.) and 2 mL of toluene were added sequentially to the tube. The mixture was stirred and activated for 15 minutes. After 15 minutes, o-aminobenzyl alcohol (123 mg, 1 mmol) and 2-methylacetophenone (188 mg, 1.4 eq.) were added sequentially to the tube. The tube was sealed and stirred at 70°C for 24 hours. The reaction was terminated and separated by column chromatography to obtain 190 mg of a white solid in an 87% yield. Characterization data for the product are as follows: 1 H NMR (500MHz, CDCl3) δ8.23–8.17(m,2H),7.86(d,J=8.1Hz,1H),7.79–7.71(m,1H),7.61-7.49(m,3H),7.40–7.30(m,3H),2.44(s,3H).

[0045] Example 3: Synthesis of 2-(3-methylphenyl)quinoline:

[0046] (Raw materials are )

[0047] A 25 mL sealed tube was added with the Mn-1 complex (15.6 mg, 3 mol%). The 25 mL sealed tube was transferred to a glove box. Inside the glove box, t-BuOK (168 mg, 1.5 eq.) and 2 mL of toluene were added sequentially to the tube. The mixture was stirred and activated for 15 minutes. After 15 minutes, o-aminobenzyl alcohol (123 mg, 1 mmol) and 3-methylacetophenone (188 mg, 1.4 eq.) were added sequentially to the tube. The tube was sealed and stirred at 70°C for 24 hours. The reaction was terminated and separated by column chromatography to yield 184 mg of a white solid (yield: 84%). Product characterization data are as follows: 1 H NMR (500MHz, CDCl3) δ8.18(d,J=8.6Hz,2H),8.00(s,1H),7.92(d,J=7.7Hz,1H),7.86–7.80(m,2 H),7.77–7.71(m,1H),7.56–7.50(m,1H),7.46–7.41(m,1H),7.30(d,J=7.5Hz,1H),2.50(s,3H).

[0048] Example 4: Synthesis of 2-(p-methylphenyl)quinoline:

[0049] (Raw materials are )

[0050] A 25 mL sealed tube was added with the Mn-1 complex (15.6 mg, 3 mol%). The 25 mL sealed tube was transferred to a glove box. Inside the glove box, t-BuOK (168 mg, 1.5 eq.) and 2 mL of toluene were added sequentially to the tube. The mixture was stirred and activated for 15 minutes. After 15 minutes, o-aminobenzyl alcohol (123 mg, 1 mmol) and 4-methylacetophenone (188 mg, 1.4 eq.) were added sequentially to the tube. The tube was sealed and stirred at 70°C for 24 hours. The reaction was terminated and separated by column chromatography to obtain 190 mg of a white solid in an 87% yield. Characterization data for the product are as follows: 1 H NMR (500MHz, CDCl3) δ8.24–8.16(m,2H),8.13–8.09(m,2H),7.84(d,J=8.5Hz,1H),7.83(d ,J=8.3Hz,1H),7.76–7.71(m,1H),7.55–7.48(m,1H),7.36(d,J=8.5Hz,2H),2.46(s,3H).

[0051] Example 5: Synthesis of 2-(p-methoxyphenyl)quinoline:

[0052] (Raw materials are )

[0053] A 25 mL sealed tube was added with the Mn-1 complex (15.6 mg, 3 mol%). The 25 mL sealed tube was transferred to a glove box. Inside the glove box, t-BuOK (168 mg, 1.5 eq.) and 2 mL of toluene were added sequentially to the tube. The mixture was stirred and activated for 15 minutes. After 15 minutes, o-aminobenzyl alcohol (123 mg, 1 mmol) and 4-methoxyacetophenone (210 mg, 1.4 eq.) were added sequentially to the tube. The tube was sealed and stirred at 70°C for 24 hours. The reaction was terminated and separated by column chromatography to yield 216 mg of a white solid (92% yield). Product characterization data are as follows: 1 H NMR (500MHz, CDCl3) δ8.18–8.12(m,4H),7.84–7.77(m,2H),7.73–7.68(m,1H),7.52–7.47(m,1H),7.05(d,J=8.5Hz,2H),3.88(s,3H).

[0054] Example 6: Synthesis of 2-(p-phenylphenyl)quinoline:

[0055] (Raw materials are )

[0056] A 25 mL sealed tube was added with the Mn-1 complex (15.6 mg, 3 mol%). The 25 mL sealed tube was transferred to a glove box. Inside the glove box, t-BuOK (168 mg, 1.5 eq.) and 2 mL of toluene were added sequentially to the tube. The mixture was stirred and activated for 15 minutes. After 15 minutes, o-aminobenzyl alcohol (123 mg, 1 mmol) and 4-phenylacetophenone (274 mg, 1.4 eq.) were added sequentially to the tube. The tube was sealed and stirred at 70°C for 24 hours. The reaction was terminated and separated by column chromatography to yield 202 mg of a white solid (yield: 72%). Product characterization data are as follows: 1 H NMR (500MHz, CDCl3) δ8.3–8.19(m,4H),7.92(d,J=8.7Hz,1H),7.84(d,J=8.1Hz,1H),7.81–7 .73(m,3H),7.69(d,J=7.2Hz,,2H),7.56–7.52(m,1H),7.52–7.46(m,2H),7.43–7.37(m,1H).

[0057] Example 7: Synthesis of 2-(4-fluorophenyl)quinoline:

[0058] (Raw materials are )

[0059] A 25 mL sealed tube was added with the Mn-1 complex (15.6 mg, 3 mol%). The 25 mL sealed tube was transferred to a glove box. Inside the glove box, t-BuOK (168 mg, 1.5 eq.) and 2 mL of toluene were added sequentially to the tube. The mixture was stirred and activated for 15 minutes. After 15 minutes, o-aminobenzyl alcohol (123 mg, 1 mmol) and 4-fluoroacetophenone (193 mg, 1.4 eq.) were added sequentially to the tube. The tube was sealed and stirred at 70°C for 24 hours. The reaction was terminated and separated by column chromatography to yield 181 mg of a white solid (yield: 81%). Characterization data for the product are as follows: 1 H NMR (500MHz, CDCl3) δ8.21(d,J=8.5Hz,1H),8.19–8.13(m,3H),7.81(d,J=8.5Hz,2H),7.77–7.72(m,1H),7.56–7.51(m,1H),7.24–7.18(m,2H).

[0060] Example 8: Synthesis of 2-(4-iodophenyl)quinoline:

[0061] (Raw materials are )

[0062] A 25 mL sealed tube was added with the Mn-1 complex (15.6 mg, 3 mol%). The 25 mL sealed tube was transferred to a glove box. Inside the glove box, t-BuOK (168 mg, 1.5 eq.) and 2 mL of toluene were added sequentially to the tube. The mixture was stirred and activated for 15 minutes. After 15 minutes, o-aminobenzyl alcohol (123 mg, 1 mmol) and 4-iodoacetophenone (344 mg, 1.4 eq.) were added sequentially to the tube. The tube was sealed and stirred at 70°C for 24 hours. The reaction was terminated and separated by column chromatography to obtain 285 mg of a white solid in an 86% yield. Characterization data for the product are as follows: 1 H NMR (500MHz, CDCl3) δ8.22–8.13(m,2H),7.94–7.88(m,2H),7.87–7.83(m,2H),7.83–7.79(m,2H),7.75–7.71(m,1H),7.56–7.51(m,1H).

[0063] Example 9: Synthesis of 2-(4-cyanophenyl)quinoline:

[0064] (Raw materials are )

[0065] A 25 mL sealed tube was added with the Mn-1 complex (15.6 mg, 3 mol%). The 25 mL sealed tube was transferred to a glove box. Inside the glove box, t-BuOK (168 mg, 1.5 eq.) and 2 mL of toluene were added sequentially to the tube. The mixture was stirred and activated for 15 minutes. After 15 minutes, o-aminobenzyl alcohol (123 mg, 1 mmol) and 4-cyanoacetophenone (203 mg, 1.4 eq.) were added sequentially to the tube. The tube was sealed and stirred at 70°C for 24 hours. The reaction was terminated and separated by column chromatography to yield 168 mg of a white solid (yield: 73%). Product characterization data are as follows: 1 H NMR (500MHz, CDCl3) δ8.40–8.28(m,3H),8.18(d,J=8.5Hz,1H),7.88–7.81(m,2H),7.78(d,J=8.4Hz,2H),7.66–7.60(m,1H),7.60–7.53(m,1H).

[0066] Example 10: Synthesis of 2-cyclopropylquinoline:

[0067] (Raw materials are )

[0068] A 25 mL sealed tube was charged with the Mn-1 complex (15.6 mg, 3 mol%). The tube was then transferred to a glove box. Inside the glove box, t-BuOK (168 mg, 1.5 eq.) and 2 mL of toluene were added sequentially to the tube. The mixture was stirred and activated for 15 minutes. After 15 minutes, o-aminobenzyl alcohol (123 mg, 1 mmol) and 1-cyclopropylethanone (118 mg, 1.4 eq.) were added sequentially to the tube. The tube was sealed and stirred at 70°C for 24 hours. The reaction was terminated and separated by column chromatography to yield 113 mg of a white solid (yield: 67%). Product characterization data are as follows: 1 H NMR (500MHz, CDCl3) δ8.01–7.94(m,2H),7.73(d,J=8.6Hz,1H),7.67–7.61(m,1H),7.45–7. 40(m,1H),7.16(d,J=8.5Hz,1H),2.28–2.22(m,1H),1.18–1.13(m,2H),1.13–1.06(m,2H).

[0069] Example 11: Synthesis of 2-ethyl-3-methylquinoline:

[0070] (Raw materials are )

[0071] A 25 mL sealed tube was added with the Mn-1 complex (15.6 mg, 3 mol%). The 25 mL sealed tube was transferred to a glove box. Inside the glove box, t-BuOK (168 mg, 1.5 eq.) and 2 mL of toluene were added sequentially to the tube. The mixture was stirred and activated for 15 minutes. After 15 minutes, o-aminobenzyl alcohol (123 mg, 1 mmol) and 2-pentanone (120 mg, 1.4 eq.) were added sequentially to the tube. The tube was sealed and stirred at 70°C for 24 hours. The reaction was terminated and separated by column chromatography to yield 137 mg of a white solid (yield: 80%). Product characterization data are as follows: 1 H NMR(500MHz, CDCl3)δ8.03(d,J=8.2Hz,1H),7.79(s,1H),7.69–7.65(m,1H),7.62– 7.56(m,1H),7.45–7.39(m,1H),3.01–2.93(m,2H),2.45(s,3H),1.39–1.36(m,3H).

[0072] Example 12: Synthesis of 2-(2-pyridine)quinoline:

[0073] (Raw materials are )

[0074] A 25 mL sealed tube was added with the Mn-1 complex (15.6 mg, 3 mol%). The 25 mL sealed tube was transferred to a glove box. Inside the glove box, t-BuOK (168 mg, 1.5 eq.) and 2 mL of toluene were added sequentially to the tube. The mixture was stirred and activated for 15 minutes. After 15 minutes, o-aminobenzyl alcohol (123 mg, 1 mmol) and 2-acetylpyridine (170 mg, 1.4 eq.) were added sequentially to the tube. The tube was sealed and stirred at 70°C for 24 hours. The reaction was terminated and separated by column chromatography to obtain 171 mg of a white solid in an 83% yield. Characterization data for the product are as follows: 1 H NMR (400MHz, CDCl3) δ8.73(d,J=4.9Hz,1H),8.65(d,J=7.9Hz,1H),8.56(d,J=8.6Hz,1H),8.26(d,J=8.8H z,1H),8.19(d,J=8.5Hz,1H),7.89–7.78(m,2H),7.76–7.67(m,1H),7.57–7.49(m,1H),7.39–7.28(m,1H).

[0075] Example 13: Synthesis of 2-(2-thiophene)quinoline:

[0076] (Raw materials are )

[0077] A 25 mL sealed tube was charged with the Mn-1 complex (15.6 mg, 3 mol%). The tube was then transferred to a glove box. Inside the glove box, t-BuOK (168 mg, 1.5 eq.) and 2 mL of toluene were added sequentially to the tube. The mixture was stirred and activated for 15 minutes. After 15 minutes, o-aminobenzyl alcohol (123 mg, 1 mmol) and 2-acetylthiophene (176 mg, 1.4 eq.) were added sequentially to the tube. The tube was sealed and stirred at 70°C for 24 hours. The reaction was terminated and separated by column chromatography to yield 160 mg of a white solid (yield: 76%). Characterization data for the product are as follows: 1 H NMR (500MHz, CDCl3) δ8.19–8.06(m,2H),7.82–7.65(m,4H),7.53–7.42(m,2H),7.17-7.14(m,1H).

[0078] Example 14: Synthesis of 8-methyl-2-phenylquinoline:

[0079] (Raw materials are )

[0080] A 25 mL sealed tube was charged with the Mn-1 complex (15.6 mg, 3 mol%). The tube was then transferred to a glove box. Inside the glove box, t-BuOK (168 mg, 1.5 eq.) and 2 mL of toluene were added sequentially to the tube. The mixture was stirred and activated for 15 minutes. After 15 minutes, the raw materials, 2-amino-3-methylbenzyl alcohol (137 mg, 1 mmol) and acetophenone (168 mg, 1.4 eq.), were added sequentially to the tube. The tube was sealed and stirred at 70°C for 24 hours. The reaction was terminated and separated by column chromatography to yield 166 mg of a white solid (yield: 76%). Product characterization data are as follows: 1 H NMR (400MHz, CDCl3) δ8.33(d,J=7.1Hz,2H),8.18(d,J=8.5Hz,1H),7.92(d,J=8.6Hz,1H),7.69(d,J=8.3 Hz,1H),7.62(d,J=7.0Hz,1H),7.60–7.55(m,2H),7.53(d,J=7.0Hz,1H),7.49–7.40(m,1H),2.99(s,3H).

[0081] Example 15: Synthesis of 7-chloro-2-phenylquinoline:

[0082] (Raw materials are )

[0083] A 25 mL sealed tube was added with the Mn-1 complex (15.6 mg, 3 mol%). The 25 mL sealed tube was transferred to a glove box. Inside the glove box, t-BuOK (168 mg, 1.5 eq.) and 2 mL of toluene were added sequentially to the tube. The mixture was stirred and activated for 15 minutes. After 15 minutes, 2-amino-7-chlorobenzyl alcohol (157 mg, 1 mmol) and acetophenone (168 mg, 1.4 eq.) were added sequentially to the tube. The tube was sealed and stirred at 80°C for 24 hours. The reaction was terminated and separated by column chromatography to obtain 209 mg of a white solid in an 87% yield. Characterization data for the product are as follows: 1 H NMR (500MHz, CDCl3) δ8.22–8.09(m,4H),7.82(d,J=8.7Hz,1H),7.70(d,J=8.7Hz,1H),7.57–7.52(m,2H),7.52–7.46(m,2H).

[0084] Example 16: Synthesis of 2,4-diphenylquinoline:

[0085] (Raw materials are )

[0086] A 25 mL sealed tube was added with the Mn-1 complex (15.6 mg, 3 mol%). The 25 mL sealed tube was transferred to a glove box. Inside the glove box, t-BuOK (168 mg, 1.5 eq.) and 2 mL of toluene were added sequentially to the tube. The mixture was stirred and activated for 15 minutes. After 15 minutes, the starting materials (2-aminophenyl)(phenyl)methanol (199 mg, 1 mmol) and acetophenone (168 mg, 1.4 eq.) were added sequentially to the tube. The tube was sealed and stirred at 80°C for 24 hours. The reaction was terminated and separated by column chromatography to obtain 169 mg of a white solid in a 60% yield. Characterization data for the product are as follows: 1 H NMR (500MHz, CDCl3) δ8.30(d,J=8.5Hz,1H),8.26(d,J=8.1Hz,2H),7.94(d,J=8. 5Hz,1H),7.85(s,1H),7.78–7.73(m,1H),7.62–7.52(m,6H),7.52–7.45(m,3H).

[0087] Example 17: Synthesis of 2-phenyl-4-[3H]quinazolinone:

[0088] (Raw materials are )

[0089] A 25 mL sealed tube was charged with the Mn-1 complex (26.0 mg, 5 mol%). The tube was then transferred to a glove box. Inside the glove box, t-BuOK (168 mg, 1.5 eq.) and 2 mL of toluene were added sequentially to the tube. The mixture was stirred and activated for 15 minutes. After 15 minutes, the raw materials, 2-aminobenzamide (136 mg, 1 mmol) and benzyl alcohol (151 mg, 1.4 eq.), were added sequentially to the tube. The tube was sealed and stirred at 100°C for 24 hours. The reaction was terminated and separated by column chromatography to yield 122 mg of a white solid (yield: 55%). Product characterization data are as follows: 1 H NMR (500MHz, DMSO) δ12.54(s,1H),8.21–8.13(m,3H),7.84–7.78(m,1H),7.77–7.70(m,1H),7.60–7.48(m,4H).

[0090] Example 18: Synthesis of 2,4,6-triphenylpyrimidine:

[0091] (Raw materials are )

[0092] A 25 mL sealed tube was added with the Mn-1 complex (26.0 mg, 5 mol%). The 25 mL sealed tube was transferred to a glove box. Inside the glove box, t-BuOK (168 mg, 1.5 eq.) and 2 mL of toluene were added sequentially to the tube. The mixture was stirred and activated for 15 minutes. After 15 minutes, the raw materials, benzamidine (120 mg, 1 mmol), acetophenone (168 mg, 1.4 eq.), and benzyl alcohol (168 mg, 1.4 eq.), were added sequentially to the tube. The tube was sealed and stirred at 100°C for 24 hours. The reaction was terminated and separated by column chromatography to obtain 163 mg of a white solid in a 53% yield. Characterization data for the product are as follows: 1 H NMR (400MHz, CDCl3) δ8.78 (d, J = 6.5 Hz, 2H), 8.31 (d, J = 7.0 Hz, 4H), 8.01 (s, 1H), 7.58 (d, J = 7.0 Hz, 9H).

[0093] Example 19: Synthesis of 2,6-diphenylpyridine:

[0094] (Raw materials are )

[0095] A 25 mL sealed tube was charged with the Mn-1 complex (26.0 mg, 5 mol%). The tube was then transferred to a glove box. Inside the glove box, t-BuOK (168 mg, 1.5 eq.) and 2 mL of toluene were added sequentially to the tube. The mixture was stirred and activated for 15 minutes. After 15 minutes, the raw materials, 3-amino-3-phenyl-1-propanol (151 mg, 1 mmol) and acetophenone (168 mg, 1.4 eq.), were added sequentially to the tube. The tube was sealed and stirred at 80°C for 24 hours. The reaction was terminated and separated by column chromatography to yield 129 mg of a white solid (yield: 56%). Product characterization data are as follows: 1 H NMR (500MHz, CDCl3) δ8.26–8.20(m,4H),7.83–7.78(m,1H),7.71(d,J=7.8Hz,2H),7.58–7.53(m,4H),7.51–7.46(m,2H).

[0096] Example 20: Synthesis of 2-phenyl-6-(p-methyl)phenylpyridine:

[0097] (Raw materials are )

[0098] A 25 mL sealed tube was charged with the Mn-1 complex (26.0 mg, 5 mol%). The tube was then transferred to a glove box. Inside the glove box, t-BuOK (168 mg, 1.5 eq.) and 2 mL of toluene were added sequentially to the tube. The mixture was stirred and activated for 15 minutes. After 15 minutes, the raw materials, 3-amino-3-phenyl-1-propanol (151 mg, 1 mmol) and p-methylacetophenone (188 mg, 1.4 eq.), were added sequentially to the tube. The tube was sealed and stirred at 80°C for 24 hours. The reaction was terminated and separated by column chromatography to yield 123 mg of a white solid (50% yield). Product characterization data are as follows: 1 H NMR (400MHz, CDCl3) δ8.24–8.14(m,2H),8.13–8.05(m,2H),7.83–7.76(m,1H),7.68(d, J=7.5Hz,2H),7.57–7.49(m,2H),7.49–7.43(m,1H),7.33(d,J=8.0Hz,2H),2.45(s,3H).

[0099] Comparative Example 1: Synthesis of 2-phenylquinoline:

[0100] (Raw materials are )

[0101] Transfer a 25 mL sealed tube to a glove box. Inside the glove box, add t-BuOK (168 mg, 1.5 eq.) and 2 mL of toluene sequentially to the tube and activate with stirring for 15 minutes. After 15 minutes, add o-aminobenzyl alcohol (123 mg, 1 mmol) and acetophenone (168 mg, 1.4 eq.) to the tube. Seal the tube tightly and stir at 70°C for 24 hours. The reaction is terminated and separated by column chromatography to obtain 80 mg of a white solid (yield: 39%).

[0102] Comparative Example 2: Synthesis of 2-phenylquinoline:

[0103] (Raw materials are )

[0104] A 25 mL sealed tube was added with the Mn-1 complex (15.6 mg, 3 mol%). The tube was then transferred to a glove box. Inside the glove box, t-BuOLi (96 mg, 1.5 eq.) and 2 mL of toluene were added sequentially to the tube. The mixture was stirred and activated for 15 minutes. After 15 minutes, o-aminobenzyl alcohol (123 mg, 1 mmol) and acetophenone (168 mg, 1.4 eq.) were added sequentially. The tube was sealed and stirred at 70°C for 24 hours. The reaction was terminated and separated by column chromatography to yield 125 mg of a white solid (yield: 61%).

[0105] Comparative Example 3: Synthesis of 2-phenylquinoline:

[0106] (Raw materials are )

[0107] A 25 mL sealed tube was added with the Mn-1 complex (15.6 mg, 3 mol%). The tube was then transferred to a glove box. Inside the glove box, t-BuOK (168 mg, 1.5 eq.) and 2 mL of toluene were added sequentially to the tube. The mixture was stirred and activated for 15 minutes. After 15 minutes, o-aminobenzyl alcohol (123 mg, 1 mmol) and acetophenone (168 mg, 1.4 eq.) were added sequentially. The tube was sealed and stirred at 50°C for 24 hours. The reaction was terminated and separated by column chromatography to yield 129 mg of a white solid (yield: 63%).

[0108] Comparative Example 4: Synthesis of 2-phenylquinoline:

[0109] (Raw materials are )

[0110] A 25 mL sealed tube was charged with the Mn-1 complex (15.6 mg, 3 mol%). The tube was then transferred to a glove box. Inside the glove box, t-BuOK (168 mg, 1.5 eq.) and 2 mL of methyl tert-butyl ether were added sequentially to the tube. The mixture was stirred and activated for 15 minutes. After 15 minutes, o-aminobenzyl alcohol (123 mg, 1 mmol) and acetophenone (168 mg, 1.4 eq.) were added sequentially. The tube was sealed and stirred at 70°C for 24 hours. The reaction was terminated and separated by column chromatography to afford 121 mg of a white solid (yield: 59%).

[0111] Finally, it should be noted that the above examples are merely specific embodiments of the present invention. Obviously, the present invention is not limited to the above examples and is susceptible to numerous variations. Any equivalent structures or equivalent processes that utilize the contents of this specification, or that are directly or indirectly applied to other related technical fields, are equally encompassed within the scope of protection of the present invention.

Claims

1. A method for synthesizing N-heterocyclic compounds using a manganese complex as catalyst, characterized in that: The method comprises: Under a nitrogen atmosphere, a tridentate nitrogen ligand manganese complex (I), a base, and a solvent are mixed and stirred uniformly. Then, amino alcohol (II) and ketone (III) are added. The temperature is raised to 40-100°C and the reaction is carried out for 24-48 hours. After post-treatment, the target product N-heterocyclic compound (IV) is obtained. in, The general formula of base can be written as: M a X b ; Wherein, M represents Na, K or Li, X represents C(CH3)3O, OH, CO3, CH3O, CH3CH2O or CH3COO, a=1-2, b=1; The structural formula of the tridentate nitrogen ligand manganese complex (I) is as follows: In formula (I), R is hydrogen, ethyl or isopropyl; The reaction raw materials amino alcohol (II) and ketone (III) and the target product N-heterocyclic compound (IV) have the following structural formula: In formula (II), formula (III) or formula (IV), R 1 is hydrogen, C1-C4 alkyl, halogen, phenyl or substituted phenyl, wherein the phenyl ring of the substituted phenyl is substituted by one or more substituents; the substituents are each independently selected from C1-C4 alkyl, halogen, C1-C4 alkoxy, trifluoromethyl, amino, nitrile or phenyl; R 2 is hydrogen or phenyl; R 3 is a C1-C4 alkyl group, a C3-C6 cycloalkyl group, a phenyl group, a substituted phenyl group or a heteroaryl group; the phenyl ring of the substituted phenyl group is substituted by one or more substituents, each of which is independently selected from a C1-C4 alkyl group, a halogen group, a C1-C4 alkoxy group, a trifluoromethyl group, an amino group, a nitrile group or a phenyl group; R 4 It is hydrogen, C1~C4 alkyl or C3~C6 cycloalkyl.

2. The method for synthesizing N-heterocyclic compounds catalyzed by a manganese complex as claimed in claim 1, characterized in that: The molar ratio of amino alcohol (II), ketone (III), base and tridentate nitrogen ligand manganese complex (I) is 1:1.2-1.8:1.0-2.0:0.01-0.

05.

3. The method for synthesizing N-heterocyclic compounds catalyzed by a manganese complex as claimed in claim 1, characterized in that: In the tridentate nitrogen ligand manganese complex (I), R is an ethyl group.

4. The method for synthesizing N-heterocyclic compounds catalyzed by a manganese complex as claimed in claim 1, characterized in that: The base was t-BuOK.

5. The method for synthesizing N-heterocyclic compounds catalyzed by a manganese complex as claimed in claim 1, characterized in that: The solvent is selected from one of toluene, 2-methyltetrahydrofuran, tetrahydrofuran, 1,4-dioxane, acetonitrile, methyl tert-butyl ether and dichloroethane.

6. The method for synthesizing N-heterocyclic compounds catalyzed by a manganese complex as claimed in claim 1, characterized in that: The post-treatment method is as follows: after the reaction is completed, the reaction solution is cooled to room temperature, water is added to quench the reaction, the aqueous phase is extracted with toluene, the organic phases are combined, dried over anhydrous sodium sulfate and then concentrated, the sample is mixed with silica gel and subjected to column chromatography separation, a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 100:1 to 50:1 is used as an eluent, the eluate containing the target product is collected, and it is evaporated to dryness under reduced pressure to obtain an N-heterocyclic compound (IV).

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