A method for preparing tetrahydroquinoxaline compounds

Abstract

The invention discloses a method for preparing a tetrahydroquinoxaline compound, the steps of which include: reacting an o-phenylenediamine compound and a prop-2-ynylsulfur ylide salt compound at room temperature in the presence of an organic solvent and a base to obtain a tetrahydroquinoxaline compound. The method of the invention has a simple process, a high yield and can be prepared in grams, and more importantly, tetrahydroquinoxaline substituted in various positions and having different substituents can be obtained at the same time, and all have excellent reaction yields, and have good industrial application prospects and potential.

Description

Technical Field

[0001] The invention belongs to the field of organic chemical synthesis and pharmaceutical intermediates, and specifically relates to a method for preparing tetrahydroquinoxaline compounds. Background Art

[0002] In the field of organic chemistry and pharmaceutical synthesis, quinoxaline compounds are important natural products and key intermediates of drug molecules, and have good antiviral, antibacterial and anti-inflammatory, anticancer, and anthelmintic biological activities. Therefore, quinoxaline compounds as key skeletons for drug construction have attracted extensive attention from chemists. So far, a variety of synthetic methods for quinoxaline compounds have appeared in the prior art. For example, Zhang Wanbin's research group (Pd(II)-Catalyzed AerobicIntermolecular 1,2-Diamination of Conjugated Dienes:A Regio-andChemoselective[4+2]Annulation for the Synthesis of Tetrahydroquinoxalines.Org.Lett.2017,19,2813–2816) reported a method for synthesizing tetrahydroquinoxaline compounds. The method uses N,N-di-p-toluenesulfonyl o-phenylenediamine and conjugated diene as raw materials, palladium acetate or copper acetate as a catalyst in the presence of oxygen to prepare the corresponding tetrahydroquinoxaline compounds. The reaction has good reaction yield and substrate universality. Xu Lijin and other chemists (Metal-free tandem cyclization / hydrosilylation to construct tetrahydroquinoxalines, Green Chem., 2018, 20, 403-410) developed a one-pot tandem reaction, using o-phenylenediamine and α-keto ester as starting materials, and tetrahydroquinoxaline compounds can be directly constructed under the catalysis of B(C6F5)3 and hydrogenation of silane. It is a very simple synthesis process. The research group of Fangrui Zhong (Intermolecular Vicinal Diaminative Assembly of Tetrahydroquinoxalines via Metal-free Oxidative [4+2] Cycloaddition Strategy, Org. Lett. 2020, 22, 2425–2430) reported a [4+2] cyclization reaction of N,N-di-p-toluenesulfonyl o-phenylenediamine oxidized by iodobenzene acetate and alkynes. The tetrahydroquinoxaline compounds were successfully prepared without the need for metal catalysts, and have very broad application prospects.

[0003] As mentioned above, although there are many methods for synthesizing tetrahydroquinoxaline compounds in the prior art, these methods have the disadvantages of unsatisfactory yield and insufficient substrate sources. Therefore, it is very necessary to develop a new and efficient method for preparing tetrahydroquinoxaline compounds. Summary of the invention

[0004] In view of the problems existing in the prior art, the object of the present invention is to provide a method for preparing tetrahydroquinoxaline compounds. The present invention can prepare tetrahydroquinoxaline compounds with fast reaction and high yield, thereby improving material utilization and meeting the extensive needs in the synthesis of pharmaceutical intermediates. The present invention obtains tetrahydroquinoxaline compounds by dissolving an alkali in an organic solvent, then adding an o-phenylenediamine compound and a prop-2-ynylsulfur ylide salt compound and mixing them for cycloaddition reaction.

[0005] The present invention provides a method for synthesizing a tetrahydroquinoxaline pharmaceutical intermediate compound represented by formula (III), the method comprising: in the presence of an organic solvent and a base, a compound of o-phenylenediamine of formula (I) and a compound of prop-2-ynylsulfur ylide salt of formula (II) are subjected to a cycloaddition reaction at room temperature to obtain the compound of formula (III).

[0006]

[0007] Wherein, R1 and R2 are each independently selected from H, halogen, alkyl or alkoxy; R3 is p-toluenesulfonyl (Ts), o-toluenesulfonyl, m-toluenesulfonyl, benzenesulfonyl (Bs), p-chlorobenzenesulfonyl, o-chlorobenzenesulfonyl or m-chlorobenzenesulfonyl; R4 is selected from H, C1-C7 alkyl, cycloalkyl or phenyl.

[0008] In the method of the present invention, the halogen atom refers to a fluorine, chlorine, bromine or iodine atom.

[0009] In the method of the present invention, C1-C7 alkyl refers to an alkyl group having 1-7 carbon atoms, which can be linear or branched, and can be, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, n-heptyl, isoheptyl, etc., without limitation.

[0010] In the method of the present invention, the base is an organic base, an alkali metal alkoxide, an alkali metal hydroxide or an alkali metal carbonate. Wherein, the base can be, for example, Et3N, DIPEA, DBU, DMAP, DABCO, sodium methoxide, sodium ethoxide, sodium tert-butoxide, potassium tert-butoxide, NaOH, KOH, sodium carbonate, potassium carbonate, rubidium carbonate, cesium carbonate, etc., or any mixture of any multiple thereof. Wherein, the base is preferably potassium carbonate, rubidium carbonate or cesium carbonate, and most preferably cesium carbonate.

[0011] In the method of the present invention, the organic solvent may be, for example, any one of tetrahydrofuran, 1,4-dioxane, toluene, dichloroethane, chloroform or acetonitrile, etc. The amount of the organic solvent is not particularly limited, and the appropriate amount may be determined, for example, based on suitability for the reaction and ease of post-treatment, which can be clearly determined by those skilled in the art according to conventional technical means.

[0012] In the method of the present invention, the molar ratio of the compound of formula (I) to the compound of formula (II) is 1:1 to 1:2, for example, 1:1, 1:1.5 or 1:2.

[0013] In the method of the present invention, the molar ratio of the compound of formula (I) to the base is 1:1-1:2, for example, 1:1, 1:1.5 or 1:2.

[0014] In the method of the present invention, the reaction temperature is 0-50°C, for example, 0°C, 25°C or 50°C.

[0015] In the method of the present invention, the reaction time is 8-24 hours, for example, 8 hours, 16 hours or 24 hours.

[0016] In the method of the present invention, after the reaction is completed, the reaction system can be naturally cooled to room temperature, concentrated in vacuo, and the residue can be chromatographed on a 200-mesh silica gel column using a mixture of petroleum ether and ethyl acetate in a volume ratio of 10:1-3:1 as an eluent to obtain the target compound, i.e., the compound of formula (III).

[0017] As described above, the present invention provides a method for synthesizing a tetrahydroquinoxaline pharmaceutical intermediate compound, provides appropriate selection and combination of reaction substrates, bases and solvents, thereby obtaining the target product in high yield, and has good industrial application prospects and potential.

[0018] The advantages of the present invention are as follows:

[0019] The method of the invention has simple process, high yield and can be prepared in gram scale. More importantly, tetrahydroquinoxaline substituted in various positions and having different substituents can be obtained at the same time, and all have excellent reaction yields and important application value. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 The compound of formula (III-2) prepared in Example 2 1 H NMR spectrum.

[0021] Figure 2 The compound of formula (III-2) prepared in Example 2 1 C NMR spectrum.

[0022] Figure 3 It is the mass spectrum of the compound represented by formula (III-2) prepared in Example 2.

[0023] Figure 4 The compound of formula (III-6) prepared in Example 6 1 H NMR spectrum.

[0024] Figure 5 The compound of formula (III-6) prepared in Example 6 1 C NMR spectrum.

[0025] Figure 6 This is the mass spectrum of the compound represented by formula (III-6) prepared in Example 6. DETAILED DESCRIPTION

[0026] The present invention is further described in detail below in conjunction with the accompanying drawings. The examples given are only used to explain the present invention but not to limit the scope of the present invention.

[0027] Example 1: Preparation of the compound shown in III-1

[0028] In a 25 ml reaction tube, 0.2 mmol of the compound of formula (I), 0.3 mmol of the compound of formula (II), 0.4 mmol of cesium carbonate and 2 mL of tetrahydrofuran were added and reacted overnight. After the reaction was completed, vacuum concentration was performed, and the residue was chromatographed on a 200 mesh silica gel column using a mixture of petroleum ether and ethyl acetate in a volume ratio of 5:1 as the eluent to obtain the target compound of formula (III-1) with a yield of 88%.

[0029]

[0030] The structure of the compound shown in III-1 is characterized as follows: 1 H NMR (500MHz, CDCl3) δ7.83(q,J=7.5Hz,J=2.0Hz,1H),7.67(q,J=7.5Hz,J=2.0Hz,1H),7.37(d,J=8.0Hz,2H),7.32(d, J=8.0Hz,2H),7.21-7.18(m,3H),7.17-7.14(m,3H),5.33(s,1H),4.95(s,1H),3.78(s,2H),2.39(s,3H),2.36(s,3H); 13C NMR (125MHz, CDCl3) δ144.8,144.2,135.4,134.4,134.3,129.8,129.7,129.6,129.5 ,127.6,127.3,125.7,125.4,125.2,123.4,112.7,48.0,21.6,21.5; HRMS(ESI)calcd for C 23 H 23 N2O4S2[M+H] + :455.1094, found 455.1086.

[0031] The NMR spectrum and mass spectrometry identified the product as having the above structure, which is the compound shown in formula III-1.

[0032] Example 2: Preparation of the compound shown in III-2

[0033] In a 25 ml reaction tube, 0.2 mmol of the compound of formula (I), 0.3 mmol of the compound of formula (II), 0.4 mmol of cesium carbonate and 2 mL of tetrahydrofuran were added and reacted overnight. After the reaction was completed, vacuum concentration was performed, and the residue was chromatographed on a 200 mesh silica gel column using a mixture of petroleum ether and ethyl acetate in a volume ratio of 5:1 as the eluent to obtain the target compound of formula (III-1) with a yield of 95%.

[0034]

[0035] The structure of the compound shown in III-2 is characterized as follows: 1 H NMR (500MHz, CDCl3) δ7.79-7.77(m,1H),7.70-7.68(m,1H),7.34(q,J=6.5Hz,J=2.0Hz,2H),7.29-7.28(m,2H),7.20-7.15(m ,4H),7.12(d,J=8.0Hz,2H),5.89(q,J=15.0Hz,J=7.5Hz,1H),3.82(s,2H),2.40(s,3H),2.35(s,3H),1.73(d,J=7.5Hz,3H); 13 C NMR (125MHz, CDCl3) δ144.6,144.1,135.5,134.6,129.8,129.5,129.4,127.6,12 7.1,126.7,125.8,125.6,125.1,122.8,42.6,21.6,21.5,13.4; HRMS(ESI)calcd for C 24 H 25 N2O4S2[M+H]+ :469.1250, found 469.1246.

[0036] The product was identified by NMR and mass spectrometry to have the above structure, which is the compound shown in formula III-2.

[0037] The compound represented by formula (III-2) 1 H NMR spectrum Figure 1 As shown, the compound represented by formula (III-2) 1 C NMR spectrum Figure 2 As shown, the mass spectrum of the compound represented by formula (III-2) is as follows Figure 3 shown.

[0038] Example 3: Preparation of the compound shown in III-3

[0039] In a 25 ml reaction tube, 0.2 mmol of the compound of formula (I), 0.3 mmol of the compound of formula (II), 0.4 mmol of cesium carbonate and 2 mL of tetrahydrofuran were added and reacted overnight. After the reaction was completed, vacuum concentration was performed, and the residue was chromatographed on a 200 mesh silica gel column using a mixture of petroleum ether and ethyl acetate in a volume ratio of 5:1 as the eluent to obtain the target compound of formula (III-1) with a yield of 87%.

[0040]

[0041] The structure of the compound shown in III-3 is characterized as follows: 1 H NMR (500MHz, CDCl3) δ7.78-7.77(m,1H),7.69-7.67(m,1H),7.35(d,J=8.0Hz ,2H),7.31(d,J=8.0Hz,2H),7.19(d,J=8.0Hz,2H),7.16-7.12(m,4H),5.87( t,J=15.5Hz,J=7.5Hz,1H),3.87(s,2H),2.40(s,3H),2.35(s,3H),2.06(q,J =15.0Hz, J=7.5Hz, 2H), 1.50-1.43 (m, 2H), 0.99 (t, J=15.0Hz, J=7.5Hz, 3H); 13 C NMR (125MHz, CDCl3) δ144.6,144.1,135.5,134.8,132.0,129.8,129.7,129.5,127.6,12 7.1,126.2,125.8,124.9,122.4,43.1,29.9,22.5,21.6,21.5,13.8; HRMS(ESI)calcdfor C 26 H29 N2O4S2[M+H] + :497.1563, found 497.1558.

[0042] The NMR spectrum and mass spectrometry identified the product as having the above structure, which is the compound shown in formula III-3.

[0043] Example 4: Preparation of the compound shown in III-4

[0044] In a 25 ml reaction tube, 0.2 mmol of the compound of formula (I), 0.3 mmol of the compound of formula (II), 0.4 mmol of cesium carbonate and 2 mL of tetrahydrofuran were added and reacted overnight. After the reaction was completed, the mixture was concentrated in vacuo, and the residue was chromatographed on a 200 mesh silica gel column using a mixture of petroleum ether and ethyl acetate in a volume ratio of 5:1 as the eluent to obtain the target compound of formula (III-1) with a yield of 89%.

[0045]

[0046] The structure of the compound shown in III-4 is characterized as follows: 1 H NMR (500MHz, CDCl3) δ7.78-7.76(m,1H),7.69-7.67(m,1H),7.35(d,J=8.5Hz,2H) ,7.31(d,J=8.0Hz,2H),7.19(d,J=8.0Hz,2H),7.16-7.12(m,4H),5.87(t,J=15.5 Hz,J=7.5Hz,1H),3.86(s,2H),2.40(s,3H),2.35(s,3H),2.07(q,J=15.0Hz,J=7. 5Hz,2H),1.44-1.41(m,2H),1.37-1.33(m,4H),0.94(t,J=13.0Hz,J=6.5Hz,3H); 13 C NMR (125MHz, CDCl3) δ144.6,144.1,135.5,134.8,132.2,129.8,129.7,129.5,127.6,127.1, 126.0,125.9,124.9,122.4,43.1,31.4,28.8,27.8,22.5,21.6,21.5,14.1; HRMS(ESI)calcd for C 28 H 33 N2O4S2[M+H] + :525.1876, found 525.1873.

[0047] The NMR spectrum and mass spectrometry identified the product as having the above structure, which is the compound shown in formula III-4.

[0048] Example 5: Preparation of the compound shown in III-5

[0049] In a 25 ml reaction tube, 0.2 mmol of the compound of formula (I), 0.3 mmol of the compound of formula (II), 0.4 mmol of cesium carbonate and 2 mL of tetrahydrofuran were added and reacted overnight. After the reaction was completed, vacuum concentration was performed, and the residue was chromatographed on a 200 mesh silica gel column using a mixture of petroleum ether and ethyl acetate in a volume ratio of 5:1 as the eluent to obtain the target compound of formula (III-1) with a yield of 90%.

[0050]

[0051] The structure of the compound shown in III-5 is characterized as follows: 1 H NMR (500MHz, CDCl3) δ7.78-7.76(m,1H),7.69-7.67(m,1H),7.35(d,J=8.0Hz, 2H),7.31(d,J=8.5Hz,2H),7.19(d,J=8.0Hz,2H),7.16-7.12(m,4H),5.87(t, J=15.5Hz, J=7.5Hz,1H),3.86(s,2H),2.40(s,3H),2.35(s,3H),2.09-2.04(m ,2H),1.43-1.40(m,2H),1.34-1.31(m,8H),0.91(t,J=13.5Hz,J=6.5Hz,3H); 13 C NMR (125MHz, CDCl3) δ144.6,144.1,135.5,134.8,132.2,129.8,129.7,129.5,127.6,127.1,12 6.0,125.9,124.9,122.4,43.1,31.8,29.2,29.1,27.9,22.7,21.6,21.5,14.1; HRMS(ESI)calcd for C 30 H 37 N2O4S2[M+H] + :553.2189, found 553.2181.

[0052] The NMR spectrum and mass spectrometry identified the product as having the above structure, which is the compound shown in formula III-5.

[0053] Example 6: Preparation of the compound shown in III-6

[0054] In a 25 ml reaction tube, 0.2 mmol of the compound of formula (I), 0.3 mmol of the compound of formula (II), 0.4 mmol of cesium carbonate and 2 mL of tetrahydrofuran were added and reacted overnight. After the reaction was completed, vacuum concentration was performed, and the residue was chromatographed on a 200 mesh silica gel column using a mixture of petroleum ether and ethyl acetate in a volume ratio of 5:1 as the eluent to obtain the target compound of formula (III-1) with a yield of 88%.

[0055]

[0056] The structure of the compound shown in III-6 is characterized as follows: 1 H NMR (500MHz, CDCl3) δ7.81-7.77(m,2H),7.34(d,J=8.0Hz,2H),7.30(d,J=8.5Hz,2H),7.20-7.15(m,4H),7.08(d,J =8.0Hz,2H),5.17(d,J=10.5Hz,1H),3.84(s,2H),2.40(s,3H),2.33(s,3H),0.97-0.93(m,2H),0.53-0.50(m,2H); 13 C NMR (125MHz, CDCl3) δ144.6,144.0,137.0,135.1,134.4,129.7,129.4,129.3,128.7,127. 7,127.4,125.5,125.3,125.2,123.4,123.1,42.5,21.6,21.5,10.3,7.7; HRMS(ESI)calcd for C 26 H 27 N2O4S2[M+H] + :495.1407,found 495.1401.

[0057] The NMR spectrum and mass spectrometry identified the product as having the above structure, which is the compound shown in formula III-6.

[0058] The compound represented by formula (III-6) 1 H NMR spectrum Figure 4 The compound represented by formula (III-6) 1 C NMR spectrum Figure 5 As shown, the mass spectrum of the compound represented by formula (III-6) is as follows Figure 6 shown.

[0059] Example 7: Preparation of the compound shown in III-7

[0060] In a 25 ml reaction tube, 0.2 mmol of the compound of formula (I), 0.3 mmol of the compound of formula (II), 0.4 mmol of cesium carbonate and 2 mL of tetrahydrofuran were added and reacted overnight. After the reaction was completed, vacuum concentration was performed, and the residue was chromatographed on a 200 mesh silica gel column using a mixture of petroleum ether and ethyl acetate in a volume ratio of 5:1 as the eluent to obtain the target compound of formula (III-1) with a yield of 85%.

[0061]

[0062] The structure of the compound shown in III-7 is characterized as follows: 1 H NMR (500MHz, CDCl3) δ7.83 (q, J=7.5Hz, J=2.0Hz, 1H), 7.73 (q, J=7.5Hz, J=2.5Hz, 1H), 7.44-7.41 (m, 4H), 7.36 (t, J=15.0Hz, J=7. 5Hz,1H),7.25-7.24(m,2H),7.22-7.19(m,2H),7.12(d,J=7.0Hz,2H),7.06-7.02(m,4H),4.09(s,2H),2.44(s,3H),2.35(s,3H); 13 C NMR (125MHz, CDCl3) δ144.9,143.9,135.2,134.6,134.1,130.9,129.9,129.5,129.3,129.2,12 8.8,128.4,127.8,127.1,127.0,125.9,125.7,125.1,122.9,43.1,21.7,21.6; HRMS(ESI)calcd for C 29 H 27 N2O4S2[M+H] + :531.1407,found 531.1401.

[0063] The NMR spectrum and mass spectrometry identified the product as having the above structure, which is the compound shown in formula III-7.

[0064] Example 8: Preparation of the compound shown in III-8

[0065] In a 25 ml reaction tube, 0.2 mmol of the compound of formula (I), 0.3 mmol of the compound of formula (II), 0.4 mmol of cesium carbonate and 2 mL of tetrahydrofuran were added and reacted overnight. After the reaction was completed, vacuum concentration was performed, and the residue was chromatographed on a 200 mesh silica gel column using a mixture of petroleum ether and ethyl acetate in a volume ratio of 5:1 as the eluent to obtain the target compound of formula (III-1) with a yield of 90%.

[0066]

[0067] The structure of the compound shown in III-8 is characterized as follows: 1 H NMR (500MHz, CDCl3) δ7.54(s,2H),7.46(s,2H),7.35(d,J=8.0Hz,2H),7.28(t,J=16.5Hz,J=8.5Hz,2H),7.19(d,J=8.0Hz,2H),7.12(d, J=8.5Hz,2H),5.84(q,J=14.5Hz,J=7.0Hz,1H),3.76(s,2H),2.40(s,3H),2.35(s,3H),2.26(s,3H),2.24(s,3H),1.68(d,J=8.0Hz,3H); 13 C NMR (125MHz, CDCl3) δ144.4,143.9,135.6,134.8,134.5,133.8,129.7,129.3,127.6,1 27.1,127.0,126.3,126.2,123.5,42.7,21.6,21.5,19.6,19.5,13.4; HRMS(ESI)calcd for C 26 H 29 N2O4S2[M+H] + :497.1563,found497.1555.

[0068] The NMR spectrum and mass spectrometry identified the product as having the above structure, which is the compound shown in formula III-8.

[0069] Example 9: Preparation of the compound shown in III-9

[0070] In a 25 ml reaction tube, 0.2 mmol of the compound of formula (I), 0.3 mmol of the compound of formula (II), 0.4 mmol of cesium carbonate and 2 mL of tetrahydrofuran were added and reacted overnight. After the reaction was completed, vacuum concentration was performed, and the residue was chromatographed on a 200 mesh silica gel column using a mixture of petroleum ether and ethyl acetate in a volume ratio of 5:1 as the eluent to obtain the target compound of formula (III-1) with a yield of 85%.

[0071]

[0072] The structure of the compound shown in III-9 is characterized as follows: 1H NMR (500MHz, CDCl3) δ8.17(s,1H),8.04(s,1H),7.84-7.81(m,1H),7.76-7.74(m,1H),7.50-7.44(m,2H),7.40-7.37(m,4H),7.18(d,J=10.0Hz ,2H),7.13(d,J=10.0Hz,2H),5.98(q,J=18.5Hz,J=9.0Hz,1H),4.05(s,2H),2.40(s,3H),2.34(s,3H),1.75(d,J=9.0Hz,3H); HRMS(ESI)calcd for C 28 H 26 N2O4S2Na[M+Na] + :541.1226, found 541.1221.

[0073] The product was identified by NMR and mass spectrometry to have the above structure, which is the compound shown in formula III-9.

[0074] Example 9: Preparation of the compound shown in III-9

[0075] In a 25 ml reaction tube, 0.2 mmol of the compound of formula (I), 0.3 mmol of the compound of formula (II), 0.4 mmol of cesium carbonate and 2 mL of tetrahydrofuran were added and reacted overnight. After the reaction was completed, vacuum concentration was performed, and the residue was chromatographed on a 200 mesh silica gel column using a mixture of petroleum ether and ethyl acetate in a volume ratio of 5:1 as the eluent to obtain the target compound of formula (III-1) with a yield of 86%.

[0076]

[0077] The structure of the compound shown in III-10 is characterized as follows: 1 H NMR (500MHz, CDCl3) δ8.09(s,1H),8.05(s,1H),7.37(J=8.5Hz,2H),7.31(J=8.5Hz,2H),7.24(J=8.5Hz,2H),7.1 7(J=8.5Hz,2H),5.91(q,J=14.5Hz,J=6.0Hz,1H),3.72(s,2H),2.43(s,3H),2.38(s,3H),1.73(d,J=7.5Hz,3H); 13C NMR (125MHz, CDCl3) δ145.2,144.8,134.8,134.1,130.0,129.7,129.2,128.9 ,127.7,126.7,125.3,121.0,120.1,41.6,21.7,21.6,13.6; HRMS(ESI)calcd forC 24 H 22 N2O4S2Br2[M+H] + :624.9461, found 624.9452.

[0078] The NMR spectrum and mass spectrometry identified the product as having the above structure, which is the compound shown in formula III-10.

[0079] Although the specific embodiments of the present invention are disclosed for the purpose of illustration, the purpose is to help understand the content of the present invention and implement it accordingly, those skilled in the art will understand that various substitutions, changes and modifications are possible without departing from the spirit and scope of the present invention and the appended claims. Therefore, the present invention should not be limited to the content disclosed in the best embodiment, and the scope of the present invention is subject to the scope defined in the claims.

Claims

1. A method for preparing a tetrahydroquinoxaline compound, comprising the steps of: In the presence of an organic solvent and a base, an o-phenylenediamine compound and a prop-2-ynylsulfur ylide salt compound are reacted at room temperature to obtain a tetrahydroquinoxaline compound; wherein, The reaction formula of o-phenylenediamine compounds and prop-2-ynylsulfur ylide salt compounds is as follows: wherein R1 and R2 are selected from H and halogen respectively; R3 is p-toluenesulfonyl, o-toluenesulfonyl, m-toluenesulfonyl, benzenesulfonyl, p-chlorobenzenesulfonyl, o-chlorobenzenesulfonyl or m-chlorobenzenesulfonyl; R4 is selected from H, C1-C7 alkyl or phenyl; The base is potassium carbonate, rubidium carbonate or cesium carbonate; The organic solvent is selected from any one of tetrahydrofuran, 1,4-dioxane, toluene, dichloroethane or acetonitrile.

2. The method according to claim 1, characterized in that The C1-C7 alkyl group refers to an alkyl group having 1 to 7 carbon atoms, and the C1-C7 alkyl group is a straight chain or a branched chain.

3. The method according to claim 2, characterized in that The C1-C7 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, n-heptyl or isoheptyl.

4. The method according to claim 1, characterized in that: The molar ratio of the o-phenylenediamine compound to the prop-2-ynylsulfur ylide salt compound is 1:1-1:2; the molar ratio of the o-phenylenediamine compound to the base is 1:1-1:2; the reaction temperature is 0-50°C; and the reaction time is 8-24 hours.

5. The method according to claim 1, characterized in that After the reaction, the reaction system was naturally cooled to room temperature and concentrated in vacuo. The residue was chromatographed on a 200-mesh silica gel column using a mixture of petroleum ether and ethyl acetate in a volume ratio of 10:1-3:1 as an eluent to obtain a tetrahydroquinoxaline compound.

6. The method according to claim 1, characterized in that Firstly, a base is dissolved in an organic solvent, and then an o-phenylenediamine compound and a prop-2-ynylsulfur ylide salt compound are added and mixed, and then a cycloaddition reaction is carried out at room temperature to obtain a tetrahydroquinoxaline compound.

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