Method for catalytically synthesizing N-heterocyclic compound by manganese complex under mild condition

Abstract

The invention discloses a method for catalytically synthesizing an N-heterocyclic compound by using a manganese complex under a mild condition, which comprises the following steps: in a nitrogen atmosphere, mixing and uniformly stirring a tridentate nitrogen ligand manganese complex (I), alkali and a solvent, then adding amino alcohol (II) and ketone (III), heating to 40-100 DEG C, reacting for 24-48 hours, and carrying out post-treatment to obtain a target product N-heterocyclic compound (IV), the method is simple to operate, mild in reaction condition, wide in reaction substrate application range, high in selectivity, stable in catalyst and high in efficiency, and has potential application value in the field of synthesis; # imgabs0 #

Description

Technical Field

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

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

[0003] The traditional method for synthesizing N-heterocyclic compounds is to use nitrogen or ammonia as a nitrogen source, and in the presence of a catalyst, react with hydrocarbons to generate N-heterocyclic compounds or react with aromatic amines and ketones to generate products with ammonia-containing heterocyclic rings. These methods are usually carried out under high temperature and high pressure conditions, and the yield is low, and the synthesis process is relatively cumbersome.

[0004] In recent years, the acceptor-free dehydrogenative coupling (ADC) process has attracted much attention because it does not require sacrificial hydrogen acceptors or the addition of additional oxidants. This process uses cheap and readily available alcohols as initial raw materials, has high atom economy, and significantly improves economic and environmental performance. On this basis, the research on the transition metal-catalyzed synthesis of N-heterocyclic compounds using alcohols as coupling agents has received widespread attention. In addition, manganese, as the third most abundant metal in the earth's crust, has a variable valence and rich coordination number, making it an extremely attractive catalyst alternative.

[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 catalytic reactions. In 2018, Maji's research group reported that a manganese complex generated in situ with tridentate nitrogen ligands 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 monovalent manganese complex synthesized quinoline, the reaction system 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 research 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-mentioned reported methods for synthesizing N-heterocyclic compounds, it can be seen that whether it is Mn(I) or Mn(II) complexes catalyzing the synthesis of N-heterocyclic compounds, the reaction temperature is above 120 degrees. Therefore, it is of great significance to develop a mild manganese catalytic system. Summary of the invention

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

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

[0010] A method for synthesizing N-heterocyclic compounds by catalysis of 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 evenly, and then amino alcohol (II) and ketone (III) are added, and the temperature is raised to 40-100° C. to react 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 reaction raw materials, tridentate nitrogen ligand manganese complex (I) is catalyst, and base is 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; the preferred base is t-BuOK;

[0016] The solvent is selected from toluene, 2-methyltetrahydrofuran, tetrahydrofuran, 1,4-dioxane, acetonitrile, methyl tert-butyl ether, and ethylene dichloride, 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 with anhydrous sodium sulfate and concentrated, the sample is mixed with silica gel for 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 evaporated to dryness under reduced pressure to obtain an 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 structural formula of the reaction raw materials amino alcohol (II) and ketone (III) and the target product N-heterocyclic compound (IV) is as follows:

[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, and the substituents are 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 C1-C4 alkyl, C3-C6 cycloalkyl, phenyl, substituted phenyl or heteroaryl; the substituted phenyl has one or more substituents on its benzene ring, each of which is independently selected from C1-C4 alkyl, halogen, C1-C4 alkoxy, trifluoromethyl, amino, nitrile or phenyl; the heteroaryl is, for example, 2-pyridyl or 2-thienyl;

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

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

[0032] The present invention utilizes a tridentate nitrogen ligand manganese complex catalyst to effectively catalyze the synthesis of N-heterocyclic compounds under mild conditions. Compared with the existing methods, the present invention is simple to operate, has mild reaction conditions, a wide range of reaction substrates, high selectivity, stable catalysts, high efficiency, and has potential application value in the field of synthesis. DETAILED DESCRIPTION

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

[0034] In the following embodiments,

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

[0036] (Raw materials are MnCl2, )

[0037] Add 2-benzimidazolyl-5,6,7,8-tetrahydroquinolin-8-one (263 mg, 1 mmol) to a 25 mL Schlenk tube, transfer the Schlenk tube to a glove box, and add anhydrous manganese chloride solid (119 mg, 0.95 eq.) to the Schlenk tube in the glove box. Transfer the Schlenk tube out of the glove box, and add 2,6-diethylaniline (165 μL, 1.0 eq.) and deoxygenated acetic acid (15 mL) to the Schlenk tube in a nitrogen atmosphere. Place the Schlenk tube in a 130 ° C oil bath and stir the reaction for 10 hours. End the reaction. At this time, a lot of solids are precipitated in the tube. After the Schlenk tube is cooled to room temperature, centrifuge the reaction solution, add dichloromethane (5 mL) to the solid obtained by centrifugation, and ultrasonically vibrate and wash until there is no ligand residue. Finally, 442 mg of light yellow green powder is obtained, with a yield of 85%.

[0038] Among them, 2,6-diethylaniline was purchased from Shanghai Aladdin Biochemical Technology Co., Ltd., 100 mL; MnCl2 was purchased from Shanghai Bid Pharmaceutical Technology Co., Ltd., 25 g; the synthesis of 2-benzimidazolyl-5,6,7,8-tetrahydroquinolin-8-one was referenced to 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] Embodiment 1: the synthesis of 2-phenylquinoline:

[0040] (Raw materials are )

[0041] Add Mn-1 complex (15.6 mg, 3 mol%) to a 25 mL sealed tube, transfer the 25 mL sealed tube to a glove box, add t-BuOK (168 mg, 1.5 eq.) and 2 mL toluene to the tube in turn in the glove box, and activate for 15 min under stirring. After 15 min, add raw materials o-aminobenzyl alcohol (123 mg, 1 mmol) and acetophenone (168 mg, 1.4 eq.) to the tube in turn, seal the tube well, and stir the reaction at 70 ° C for 24 h. End the reaction, and separate by column chromatography to obtain 184 mg of white solid, with a yield of 90%. The product characterization data 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] Add Mn-1 complex (15.6 mg, 3 mol%) to a 25 mL sealed tube, transfer the 25 mL sealed tube to a glove box, add t-BuOK (168 mg, 1.5 eq.) and 2 mL toluene to the tube in turn in the glove box, and activate for 15 min under stirring. After 15 min, add raw materials o-aminobenzyl alcohol (123 mg, 1 mmol) and 2-methylacetophenone (188 mg, 1.4 eq.) to the tube in turn, seal the tube well, and stir the reaction at 70 ° C for 24 h. End the reaction, and separate by column chromatography to obtain 190 mg of white solid, with a yield of 87%. The product characterization data 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] Add Mn-1 complex (15.6 mg, 3 mol%) to a 25 mL sealed tube, transfer the 25 mL sealed tube to a glove box, add t-BuOK (168 mg, 1.5 eq.) and 2 mL toluene to the tube in turn in the glove box, and activate for 15 min under stirring. After 15 min, add raw materials o-aminobenzyl alcohol (123 mg, 1 mmol) and 3-methylacetophenone (188 mg, 1.4 eq.) to the tube in turn, seal the tube, and stir the reaction at 70 ° C for 24 h. End the reaction, and separate by column chromatography to obtain 184 mg of white solid, with a yield of 84%. The 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] Add Mn-1 complex (15.6 mg, 3 mol%) to a 25 mL sealed tube, transfer the 25 mL sealed tube to a glove box, add t-BuOK (168 mg, 1.5 eq.) and 2 mL toluene to the tube in turn in the glove box, and activate for 15 min under stirring. After 15 min, add raw materials o-aminobenzyl alcohol (123 mg, 1 mmol) and 4-methylacetophenone (188 mg, 1.4 eq.) to the tube in turn, seal the tube well, and stir the reaction at 70 ° C for 24 h. End the reaction, and separate by column chromatography to obtain 190 mg of white solid, with a yield of 87%. The product characterization data 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] Add Mn-1 complex (15.6 mg, 3 mol%) to a 25 mL sealed tube, transfer the 25 mL sealed tube to a glove box, add t-BuOK (168 mg, 1.5 eq.) and 2 mL toluene to the tube in turn in the glove box, and activate for 15 min under stirring. After 15 min, add raw materials o-aminobenzyl alcohol (123 mg, 1 mmol) and 4-methoxyacetophenone (210 mg, 1.4 eq.) to the tube in turn, seal the tube well, and stir the reaction at 70 ° C for 24 h. End the reaction, and separate by column chromatography to obtain 216 mg of white solid, with a yield of 92%. The 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] Add Mn-1 complex (15.6 mg, 3 mol%) to a 25 mL sealed tube, transfer the 25 mL sealed tube to a glove box, add t-BuOK (168 mg, 1.5 eq.) and 2 mL toluene to the tube in turn in the glove box, and activate for 15 min under stirring. After 15 min, add raw materials o-aminobenzyl alcohol (123 mg, 1 mmol) and 4-phenylacetophenone (274 mg, 1.4 eq.) to the tube in turn, seal the tube, and stir the reaction at 70 ° C for 24 h. End the reaction, and separate by column chromatography to obtain 202 mg of white solid, with a yield of 72%. The 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] Add Mn-1 complex (15.6 mg, 3 mol%) to a 25 mL sealed tube, transfer the 25 mL sealed tube to a glove box, add t-BuOK (168 mg, 1.5 eq.) and 2 mL toluene to the tube in turn in the glove box, and activate for 15 min under stirring. After 15 min, add raw materials o-aminobenzyl alcohol (123 mg, 1 mmol) and 4-fluoroacetophenone (193 mg, 1.4 eq.) to the tube in turn, seal the tube, and stir the reaction at 70 ° C for 24 h. End the reaction, and separate by column chromatography to obtain 181 mg of white solid, with a yield of 81%. The product characterization data 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] Add Mn-1 complex (15.6 mg, 3 mol%) to a 25 mL sealed tube, transfer the 25 mL sealed tube to a glove box, add t-BuOK (168 mg, 1.5 eq.) and 2 mL toluene to the tube in turn in the glove box, and activate for 15 min under stirring. After 15 min, add raw materials o-aminobenzyl alcohol (123 mg, 1 mmol) and 4-iodoacetophenone (344 mg, 1.4 eq.) to the tube in turn, seal the tube, and stir the reaction at 70 ° C for 24 h. End the reaction, and separate by column chromatography to obtain 285 mg of white solid, with a yield of 86%. The product characterization data 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] Add Mn-1 complex (15.6 mg, 3 mol%) to a 25 mL sealed tube, transfer the 25 mL sealed tube to a glove box, add t-BuOK (168 mg, 1.5 eq.) and 2 mL toluene to the tube in turn in the glove box, and activate for 15 min under stirring. After 15 min, add raw materials o-aminobenzyl alcohol (123 mg, 1 mmol) and 4-cyanoacetophenone (203 mg, 1.4 eq.) to the tube in turn, seal the tube, and stir the reaction at 70 ° C for 24 h. End the reaction, and separate by column chromatography to obtain 168 mg of white solid, with a yield of 73%. The 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] Add Mn-1 complex (15.6 mg, 3 mol%) to a 25 mL sealed tube, transfer the 25 mL sealed tube to a glove box, add t-BuOK (168 mg, 1.5 eq.) and 2 mL toluene to the tube in turn in the glove box, and activate for 15 min under stirring. After 15 min, add raw materials o-aminobenzyl alcohol (123 mg, 1 mmol) and 1-cyclopropylethyl ketone (118 mg, 1.4 eq.) to the tube in turn, seal the tube well, and stir the reaction at 70 ° C for 24 h. End the reaction, and separate by column chromatography to obtain 113 mg of white solid, with a yield of 67%. The 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] Add Mn-1 complex (15.6 mg, 3 mol%) to a 25 mL sealed tube, transfer the 25 mL sealed tube to a glove box, add t-BuOK (168 mg, 1.5 eq.) and 2 mL toluene to the tube in turn in the glove box, and activate for 15 min under stirring. After 15 min, add raw materials o-aminobenzyl alcohol (123 mg, 1 mmol) and 2-pentanone (120 mg, 1.4 eq.) to the tube in turn, seal the tube well, and stir the reaction at 70 ° C for 24 h. End the reaction, and separate by column chromatography to obtain 137 mg of white solid, with a yield of 80%. The 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] Add Mn-1 complex (15.6 mg, 3 mol%) to a 25 mL sealed tube, transfer the 25 mL sealed tube to a glove box, add t-BuOK (168 mg, 1.5 eq.) and 2 mL toluene to the tube in turn in the glove box, and activate for 15 min under stirring. After 15 min, add raw materials o-aminobenzyl alcohol (123 mg, 1 mmol) and 2-acetylpyridine (170 mg, 1.4 eq.) to the tube in turn, seal the tube well, and stir the reaction at 70 ° C for 24 h. End the reaction, and separate by column chromatography to obtain 171 mg of white solid, with a yield of 83%. The product characterization data 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] Add Mn-1 complex (15.6 mg, 3 mol%) to a 25 mL sealed tube, transfer the 25 mL sealed tube to a glove box, add t-BuOK (168 mg, 1.5 eq.) and 2 mL toluene to the tube in turn in the glove box, and activate for 15 min under stirring. After 15 min, add raw materials o-aminobenzyl alcohol (123 mg, 1 mmol) and 2-acetylthiophene (176 mg, 1.4 eq.) to the tube in turn, seal the tube, and stir the reaction at 70 ° C for 24 h. End the reaction, and separate by column chromatography to obtain 160 mg of white solid, with a yield of 76%. The product characterization data 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] Add Mn-1 complex (15.6 mg, 3 mol%) to a 25 mL sealed tube, transfer the 25 mL sealed tube to a glove box, add t-BuOK (168 mg, 1.5 eq.) and 2 mL toluene to the tube in turn in the glove box, and activate for 15 min under stirring. After 15 min, add raw materials 2-amino-3-methylbenzyl alcohol (137 mg, 1 mmol) and acetophenone (168 mg, 1.4 eq.) to the tube in turn, seal the tube well, and stir the reaction at 70 ° C for 24 h. End the reaction, and separate by column chromatography to obtain 166 mg of white solid, with a yield of 76%. The 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] Add Mn-1 complex (15.6 mg, 3 mol%) to a 25 mL sealed tube, transfer the 25 mL sealed tube to a glove box, add t-BuOK (168 mg, 1.5 eq.) and 2 mL toluene to the tube in turn in the glove box, and activate for 15 min under stirring. After 15 min, add 2-amino-7-chlorobenzyl alcohol (157 mg, 1 mmol) and acetophenone (168 mg, 1.4 eq.) to the tube in turn, seal the tube, and stir the reaction at 80 ° C for 24 h. End the reaction, and separate by column chromatography to obtain 209 mg of a white solid, with a yield of 87%. The product characterization data 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] Add Mn-1 complex (15.6 mg, 3 mol%) to a 25 mL sealed tube, transfer the 25 mL sealed tube to a glove box, add t-BuOK (168 mg, 1.5 eq.) and 2 mL toluene to the tube in turn in the glove box, and activate for 15 min under stirring. After 15 min, add raw materials (2-aminophenyl)(phenyl)methanol (199 mg, 1 mmol) and acetophenone (168 mg, 1.4 eq.) to the tube in turn, seal the tube, and stir the reaction at 80 ° C for 24 h. End the reaction, and separate by column chromatography to obtain 169 mg of white solid, with a yield of 60%. The product characterization data 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] Add Mn-1 complex (26.0 mg, 5 mol%) to a 25 mL sealed tube, transfer the 25 mL sealed tube to a glove box, add t-BuOK (168 mg, 1.5 eq.) and 2 mL toluene to the tube in turn in the glove box, and activate for 15 min under stirring. After 15 min, add raw materials 2-aminobenzamide (136 mg, 1 mmol) and benzyl alcohol (151 mg, 1.4 eq.) to the tube in turn, seal the tube, and stir the reaction at 100 ° C for 24 h. End the reaction, and separate by column chromatography to obtain 122 mg of white solid, with a yield of 55%. The 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] Add Mn-1 complex (26.0 mg, 5 mol%) to a 25 mL sealed tube, transfer the 25 mL sealed tube to a glove box, add t-BuOK (168 mg, 1.5 eq.) and 2 mL toluene to the tube in turn in the glove box, and activate for 15 min under stirring. After 15 min, add raw materials benzamidine (120 mg, 1 mmol), acetophenone (168 mg, 1.4 eq.) and benzyl alcohol (168 mg, 1.4 eq.) to the tube in turn, seal the tube, and stir the reaction at 100 ° C for 24 h. End the reaction, and separate by column chromatography to obtain 163 mg of white solid, with a yield of 53%. The product characterization data 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] Add Mn-1 complex (26.0 mg, 5 mol%) to a 25 mL sealed tube, transfer the 25 mL sealed tube to a glove box, add t-BuOK (168 mg, 1.5 eq.) and 2 mL toluene to the tube in turn in the glove box, and activate for 15 min under stirring. After 15 min, add raw materials 3-amino-3-phenyl-1-propanol (151 mg, 1 mmol) and acetophenone (168 mg, 1.4 eq.) to the tube in turn, seal the tube, and stir the reaction at 80 ° C for 24 h. End the reaction, and separate by column chromatography to obtain 129 mg of white solid, with a yield of 56%. The 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] Add Mn-1 complex (26.0 mg, 5 mol%) to a 25 mL sealed tube, transfer the 25 mL sealed tube to a glove box, add t-BuOK (168 mg, 1.5 eq.) and 2 mL toluene to the tube in turn in the glove box, and activate for 15 min under stirring. After 15 min, add raw materials 3-amino-3-phenyl-1-propanol (151 mg, 1 mmol) and p-methylacetophenone (188 mg, 1.4 eq.) to the tube in turn, seal the tube, and stir the reaction at 80 ° C for 24 h. End the reaction, and separate by column chromatography to obtain 123 mg of white solid, with a yield of 50%. The 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 the 25mL sealed tube to the glove box, add t-BuOK (168mg, 1.5eq.) and 2mL toluene to the tube in turn, and activate for 15min under stirring. After 15min, add the raw materials o-aminobenzyl alcohol (123mg, 1mmol) and acetophenone (168mg, 1.4eq.) to the tube in turn, seal the tube, and stir the reaction at 70℃ for 24h. End the reaction, and separate by column chromatography to obtain 80mg of white solid, with a yield of 39%.

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

[0103] (Raw materials are )

[0104] Add Mn-1 complex (15.6 mg, 3 mol%) to a 25 mL sealed tube, transfer the 25 mL sealed tube to a glove box, add t-BuOLi (96 mg, 1.5 eq.) and 2 mL toluene to the tube in turn in the glove box, and activate for 15 min under stirring. After 15 min, add raw materials o-aminobenzyl alcohol (123 mg, 1 mmol) and acetophenone (168 mg, 1.4 eq.) to the tube in turn, seal the tube, and stir the reaction at 70 ° C for 24 h. End the reaction, and separate by column chromatography to obtain 125 mg of white solid, with a yield of 61%.

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

[0106] (Raw materials are )

[0107] Add Mn-1 complex (15.6 mg, 3 mol%) to a 25 mL sealed tube, transfer the 25 mL sealed tube to a glove box, add t-BuOK (168 mg, 1.5 eq.) and 2 mL toluene to the tube in turn in the glove box, and activate for 15 min under stirring. After 15 min, add raw materials o-aminobenzyl alcohol (123 mg, 1 mmol) and acetophenone (168 mg, 1.4 eq.) to the tube in turn, seal the tube, and stir the reaction at 50 ° C for 24 h. End the reaction, and separate by column chromatography to obtain 129 mg of white solid, with a yield of 63%.

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

[0109] (Raw materials are )

[0110] Add Mn-1 complex (15.6 mg, 3 mol%) to a 25 mL sealed tube, transfer the 25 mL sealed tube to a glove box, add t-BuOK (168 mg, 1.5 eq.) and 2 mL methyl tert-butyl ether to the tube in turn, and activate for 15 min under stirring. After 15 min, add raw materials o-aminobenzyl alcohol (123 mg, 1 mmol) and acetophenone (168 mg, 1.4 eq.) to the tube in turn, seal the tube, and stir the reaction at 70 ° C for 24 h. End the reaction, and separate by column chromatography to obtain 121 mg of white solid, with a yield of 59%.

[0111] Finally, it should be noted that the above are only some specific embodiments of the present invention. Obviously, the present invention is not limited to the above embodiments, and there are many variations. Any equivalent structure or equivalent process transformation made by using the contents of the present invention specification, or directly or indirectly applied in other related technical fields, are also included in the protection scope 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 evenly, and then amino alcohol (II) and ketone (III) are added, and the temperature is raised to 40-100° C. to react 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 structural formula of the reaction raw materials amino alcohol (II) and ketone (III) and the target product N-heterocyclic compound (IV) is as follows: 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 C1-C4 alkyl, C3-C6 cycloalkyl, phenyl, substituted phenyl or heteroaryl; the phenyl ring of the substituted phenyl is substituted by one or more substituents, and the substituents are independently selected from C1-C4 alkyl, halogen, C1-C4 alkoxy, trifluoromethyl, amino, nitrile or phenyl; R 4 It is hydrogen, C1~C4 alkyl or C3~C6 cycloalkyl.

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

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

6. The method for synthesizing N-heterocyclic compounds catalyzed by manganese complexes 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 with anhydrous sodium sulfate and then concentrated, the sample is mixed with silica gel for column chromatography separation, and 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 evaporated to dryness under reduced pressure to obtain an N-heterocyclic compound (IV).

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