A method for synthesizing nitrogen-containing heterocyclic compounds using rare earth catalysis

Abstract

This invention discloses a rare-earth catalytic method for synthesizing nitrogen-containing heterocyclic compounds. Using toluene as a solvent, p-trifluoromethylaniline as an additive, and pinacolborane as a hydrogen source, under a nitrogen atmosphere, bis(trimethylsilylaminoyttrium) and tris(pentafluorophenyl)borane are used as catalysts to co-catalyze the hydrogen transfer reduction reaction of acridine / quinoxaline compounds, thereby achieving the preparation of structurally diverse tetrahydroacridine / tetrahydroquinoxaline. This invention has advantages such as wide availability of raw materials, simple and easily prepared catalysts, convenient operation, high selectivity, high yield, mild reaction conditions, and broad applicability.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically a method for synthesizing nitrogen-containing heterocyclic compounds using rare earth catalysis. Background Technology

[0002] Tetrahydroacrimidine / tetrahydroquinoxaline compounds are ubiquitous structural motifs in naturally occurring alkaloids and many bioactive compounds, and are also important components of drug synthesis, agrochemical synthesis, and materials science. Metal-catalyzed catalytic hydrogenation of acridine / quinoxaline benzothiazole with hydrogen molecules is a common method for preparing tetrahydroacrimidine / tetrahydroquinoxaline. Tetrahydroacrimidine / tetrahydroquinoxaline can also be prepared by catalytic hydrogen transfer reduction (Chem. Commun. 2017, 53, 9269). However, these reactions have certain limitations, including cumbersome catalyst preparation, harsh reaction conditions, narrow substrate scope, low functional compatibility, poor chemoselectivity, and the generation of large amounts of toxic waste. Summary of the Invention

[0003] The purpose of this invention is to overcome the shortcomings of the prior art and provide a method for synthesizing nitrogen-containing heterocyclic compounds using rare earth catalysis. This invention uses widely available raw materials, has a simple and easy-to-obtain catalyst, is easy to operate, has high selectivity, high yield, and mild reaction conditions.

[0004] The objective of this invention is achieved through the following technical solution: a method for synthesizing nitrogen-containing heterocyclic compounds using rare earth catalysts, wherein bis(trimethylsilylaminoyttrium) and tris(pentafluorophenyl)borane are used as catalysts to catalyze acridine or quinoxaline to obtain the corresponding nitrogen-containing heterocyclic compounds.

[0005] As one possible embodiment, the molar ratio of bis(trimethylsilylaminoyttrium) to tris(pentafluorophenyl)borane is 1:1.

[0006] As one possible embodiment, the reaction uses trifluoromethylaniline as an additive, toluene as a solvent, and pinacol borane as a hydrogen source.

[0007] As one possible embodiment, the molar ratio of acridine or quinoxaline, bis(trimethylsilylaminoyttrium), tri(pentafluorophenyl)borane, p-trifluoromethylaniline and pinacolborane is 1:0.1:0.1:0.1:5.0.

[0008] The synthetic reaction formula for a rare earth-catalyzed nitrogen-containing heterocyclic compound is as follows:

[0009]

[0010] As one possible embodiment, R is hydrogen or any one of ortho-phenyl, methyl, and chlorine.

[0011] The beneficial effects of this invention are: under the catalytic system of bis(trimethylsilylaminoyttrium) / tris(pentafluorophenyl)borane, acridine / quinoxaline compounds undergo hydrogen transfer reduction reaction, thereby achieving the synthesis of structurally diverse tetrahydroacridine / tetrahydroquinoxaline.

[0012] (1) The raw materials of this invention are widely available, the operation is simple, the applicability is broad, the selectivity is high, and the environmental protection and substrate applicability are significantly improved.

[0013] (2) The tetrahydroacrylidine / tetrahydroquinoxaline compounds of the present invention have high yields, with reaction yields of over 90%, and high quality, and are easy to process after post-processing.

[0014] (3) This invention is an important supplement to the preparation of tetrahydroacridine / tetrahydroquinoxaline compounds and provides important ideas for the synthesis of bioactive compounds. Attached Figure Description

[0015] Figure 1 The proton NMR spectrum of Example 1;

[0016] Figure 2 The carbon NMR spectrum of Example 1;

[0017] Figure 3 The proton NMR spectrum of Example 2;

[0018] Figure 4 The nuclear magnetic resonance carbon spectrum of Example 2;

[0019] Figure 5 The 1H NMR spectrum of Example 3;

[0020] Figure 6 The carbon NMR spectrum of Example 3;

[0021] Figure 7 The proton NMR spectrum of Example 4;

[0022] Figure 8 The carbon NMR spectrum of Example 4;

[0023] Figure 9 The proton NMR spectrum of Example 5;

[0024] Figure 10 The carbon NMR spectrum of Example 5;

[0025] Figure 11 The proton NMR spectrum of Example 6;

[0026] Figure 12 This is the carbon NMR spectrum of Example 6. Detailed Implementation

[0027] The technical solution of the present invention will be further described in detail below with reference to the accompanying drawings, but the scope of protection of the present invention is not limited to the following description.

[0028] Example 1

[0029] The preparation of tetrahydroacridine, with the following structural formula:

[0030]

[0031] The specific method includes the following steps:

[0032] 0.5 mmol acridine, 0.05 mmol bis(trimethylsilyl)yttrium, 0.05 mmol tri(pentafluorophenyl)borane, 0.05 mmol p-trifluoromethylaniline, 2.5 mmol pinacolborane, and 1.5 mL toluene were reacted at 50 °C for 12 hours.

[0033] The product separation yield was 93%. The product was analyzed, and the results are as follows: Figures 1-2 .

[0034] 1 H NMR (400MHz, DMSO) δ8.64(s,1H),7.09-6.99(m,4H),6.81-6.72(m,4H),3.95(s,2H); 13 C NMR (101MHz, DMSO) δ141.2,128.8,127.3,120.1,119.5,113.8,31.2.

[0035] Example 2

[0036] The preparation of 2-phenyltetrahydroacridine, with the following structural formula:

[0037]

[0038] The specific method includes the following steps:

[0039] 0.5 mmol 2-phenylacridine, 0.05 mmol bis(trimethylsilyl)yttrium, 0.05 mmol tris(pentafluorophenyl)borane, 0.05 mmol p-trifluoromethylaniline, 2.5 mmol pinacolborane, and 1.5 mL toluene were reacted at 50 °C for 12 hours.

[0040] The product separation yield was 96%. The product was analyzed, and the results are as follows: Figures 3-4 .

[0041] 1H NMR (400MHz, DMSO) δ8.97 (s, 1H), 7.25-7.14 (m, 4H), 7.13-7.05 (m, 5H), 6.94 (d, J = 7.7Hz, 2H), 6.82-6.70 (m, 2H), 5.32 (s, 1H); 13 C NMR (101MHz, DMSO) δ148.7,140.0,129.7,128.9,127.62,127.61,126.5,123.3,120.4,114.4,47.1.

[0042] Example 3

[0043] The preparation of tetrahydroquinoxaline, with the following structural formula:

[0044]

[0045] The specific method includes the following steps:

[0046] 0.5 mmol quinoxaline, 0.05 mmol equiv bis(trimethylsilyl)yttrium, 0.05 mmol equiv tris(pentafluorophenyl)borane, 0.05 mmol p-trifluoromethylaniline, 2.5 mmol pinacolborane, and 1.5 mL toluene were reacted at 50 °C for 12 hours.

[0047] The product separation yield was 95%. The product was analyzed, and the results are as follows: Figures 5-6 .

[0048] 1 H NMR (400MHz, CDCl3) δ6.55(s,2H),6.48(s,2H),3.39(s,4H); 13 C NMR (101MHz, CDCl3) δ133.8,118.9,114.8,41.5.

[0049] Example 4

[0050] The preparation of 2-methyltetrahydroquinoxaline, with the following structural formula:

[0051]

[0052] The specific method includes the following steps:

[0053] 0.5 mmol 2-methylquinoxaline, 0.05 mmol bis(trimethylsilyl)yttrium, 0.05 mmol tris(pentafluorophenyl)borane, 0.05 mmol p-trifluoromethylaniline, 2.5 mmol pinacolborane, and 1.5 mL toluene were reacted at 50 °C for 12 hours.

[0054] The product separation yield was 88%. The product was analyzed, and the results are as follows: Figures 7-8 .

[0055] 1 H NMR (400MHz, CDCl3) δ6.70 (dd, J=5.4, 3.7Hz, 2H), 6.60 (dd, J=5.2, 2.6Hz, 2H), 3.74- 3.48(m,3H),3.40(dd,J=10.7,2.7Hz,1H),3.13(t,J=9.4Hz,1H),1.32-1.23(m,3H); 13 C NMR (101MHz, CDCl3) δ133.6,133.2,118.6,114.48,114.42,48.2,45.7,19.9.

[0056] Example 5

[0057] The preparation of 5-methyltetrahydroquinoxaline, with the following structural formula:

[0058]

[0059] The specific method includes the following steps:

[0060] 0.5 mmol 5-methylquinoxaline, 0.05 mmol bis(trimethylsilyl)yttrium, 0.05 mmol tris(pentafluorophenyl)borane, 0.05 mmol p-trifluoromethylaniline, 2.5 mmol pinacolborane, and 1.5 mL toluene were reacted at 50 °C for 12 hours.

[0061] The product separation yield was 91%. The product was analyzed, and the results are as follows: Figures 9-10 .

[0062] 1 H NMR (400MHz, CDCl3) δ6.65-6.51(m,2H),6.43(dd,J=6.7,2.6Hz,1H),3.63-3.47(m,4H),3.46-3.39(m,2H),2.12(s,3H). 13 C NMR (101MHz, CDCl3) δ133.2,131.7,122.2,120.4,118.0,112.9,41.8,41.2,17.0.

[0063] Example 6

[0064] The preparation of 6-chlorotetrahydroquinoxaline, with the following structural formula:

[0065]

[0066] The specific method includes the following steps:

[0067] 0.5 mmol 6-chloroquinoxaline, 0.05 mmol bis(trimethylsilyl)yttrium, 0.05 mmol tris(pentafluorophenyl)borane, 0.05 mmol p-trifluoromethylaniline, 2.5 mmol pinacolborane, and 1.5 mL toluene were reacted at 50 °C for 12 hours.

[0068] The product separation yield was 92%. The product was analyzed, and the results are as follows: Figures 11-12 .

[0069] 1 H NMR (400MHz, CDCl3) δ6.51(dd,J=8.3,2.3Hz,1H),6.44(d,J=2.3Hz,1H),6.38(d,J=8.2Hz,1H),3.58(s,2H),3.38(s,4H). 13 C NMR (150MHz, CDCl3) δ134.8,132.0,123.3,118.0,115.4,114.0,4.

[0070] Comparative Example 1

[0071] Based on Example 1, using only bis(trimethylsilylaminoyttrium) as a catalyst, the yield was 71%.

[0072] Comparative Example 2

[0073] Based on Example 1, using only tris(pentafluorophenyl)borane as a catalyst, the yield was 66%.

[0074] The above description is merely a preferred embodiment of the present invention. It should be understood that the present invention is not limited to the forms disclosed herein and should not be construed as excluding other embodiments. It can be used in various other combinations, modifications, and environments, and can be altered within the scope of the concept described herein through the above teachings or related technologies or knowledge. Modifications and variations made by those skilled in the art that do not depart from the spirit and scope of the present invention should be within the protection scope of the appended claims.

Claims

1. A method for synthesizing nitrogen-containing heterocyclic compounds using rare earth catalysis, characterized in that: Tetrahydroacridine was obtained by catalysis of acridine with bis(trimethylsilylaminoyttrium) and tris(pentafluorophenyl)borane. Tetrahydroquinoxaline was obtained by catalysis of quinoxaline with bis(trimethylsilylaminoyttrium) and tris(pentafluorophenyl)borane; The reaction used trifluoromethylaniline as an additive, toluene as a solvent, and pinacol borane as a hydrogen source.

2. The method for synthesizing rare earth-catalyzed nitrogen-containing heterocyclic compounds according to claim 1, characterized in that: The molar ratio of bis(trimethylsilylaminoyttrium) to tris(pentafluorophenyl)borane is 1:

1.

3. The method for synthesizing rare earth-catalyzed nitrogen-containing heterocyclic compounds according to claim 1, characterized in that: The molar ratio of acridine or quinoxaline, bis(trimethylsilylaminoyttrium), tris(pentafluorophenyl)borane, p-trifluoromethylaniline and pinacolborane is 1:0.1:0.1:0.1:5.

0.

4. A method for synthesizing nitrogen-containing heterocyclic compounds using rare earth catalysis, characterized in that: The reaction formula for the synthesis method is: ； Formula I is 2-phenylacridine, 2-methylquinoxaline, 5-methylquinoxaline, or 6-chloroquinoxaline; When Formula I is 2-phenylacridine, Formula II is 2-phenyltetrahydroacridine; When Formula I is 2-methylquinoxaline, Formula II is 2-methyltetrahydroquinoxaline; When Formula I is 5-methylquinoxaline, Formula II is 5-methyltetrahydroquinoxaline; When Formula I is 6-chloroquinoxaline, Formula II is 6-chlorotetrahydroquinoxaline.

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