A green method for synthesis of [1,2]thiazine derivatives

Abstract

The application discloses a green method for synthesizing [1,2] thiazine derivative, and belongs to the technical field of green chemistry and organic synthesis. The [1,2] thiazine derivative containing alkane, alkene, halogen and heterocycle is prepared under the condition of room temperature, openness and neutrality, and a catalyst is MBr x (M is Fe 2+ , Fe 3+ , Ce 3+ , etc., and x is 2-3), and the only oxidant is H2O2. The application realizes the synthesis and preparation of [1,2] thiazine derivative with H2O2 as an oxidant for the first time, and the catalytic reaction is green and sustainable, and the use of expensive and complex catalysts is avoided. The by-product is H2O, and the problems of environmental damage and low yield caused by catalytic reactions of many other strong oxidants are solved. The application has the advantages of mild reaction condition, simple reaction process, high yield, safety, environmental protection, conformity to the green chemistry concept, wider applicability, wide development prospect and application prospect, and can be widely applied in the fields of organic synthesis, medicine, pesticide and probe, etc.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of green chemistry and organic synthesis, in particular to a green method for preparing a new [1,2]thiazine derivative containing aryl, aromatic heterocycle, pyridine ring, alkyl, alkenyl, alicyclic hydrocarbon, ester group, cyano group, carboxyl group. BACKGROUND

[0002] Thiazine compounds are an important class of nitrogen-containing heterocyclic compounds, which have certain drug effects and wide biological activities, and are also intermediates of many natural products and drug active molecules, and have wide applications in the fields of medicine, agricultural chemistry, biochemistry and material chemistry. Among them, the formation of thiazine imine in [1,2]thiazine derivatives is a necessary condition for the development of biological tissues, and the thiazine imine also plays a role as a nitro transfer reagent in organic synthesis, and plays a key role in electrocyclization, aralkyl thiamination and other reactions. In addition, [1,2]thiazine derivatives can also be used as fluorescent probes and have wide applications in various detection and labeling, such as determination of metal ions, pesticide residues, biological molecule content, tracing of biological molecules, labeling of macromolecules, etc.

[0003] At present, many methods for synthesizing [1,2]thiazine derivatives by cyclization of sulfide and amino group have been developed, including N-bromosuccinimide (NBS), meta-chloroperoxybenzoic acid (m-CPBA), tert-butyl hypochlorite (t-BuOCl), dimethyl sulfoxide (DMSO / H + ), sodium periodate (NaIO4), metal catalysis (such as Pb(OAc)4, OsO4), potassium peroxymonosulfate (Oxone-KBr) and enzyme conversion (such as haloperoxidase), but these methods have many shortcomings, such as the wide use of strong oxidants which may cause safety problems, and the production of toxic and harmful by-products in the reaction process which may pose a great threat to the environment and human health. Therefore, it is of great significance to develop a green, safe, inexpensive and widely applicable method for preparing [1,2]thiazine derivatives. SUMMARY

[0004] The purpose of the present application is to develop a green and efficient method for synthesizing [1,2]thiazine derivatives, which is used for preparing [1,2]thiazine derivatives containing aryl, aromatic heterocycle, pyridine ring, alkyl, alkenyl, alicyclic hydrocarbon, ester group, cyano group, carboxyl group formed by intramolecular cyclization.

[0005] The technical scheme adopted by the present application is as follows:

[0006] A green method for preparing [1,2]thiazine derivatives:

[0007] Under room temperature and neutral conditions, MBr x (M is Fe 2+Fe 3+ Ce 3+ Ce 2+ Fe 3+ Ce 3+ Fe

[0008] The reaction uses a thiol with an alkane, alkene, arene, oxazole, thiazole, pyrazole, imidazole, and derivatives thereof as the starting material, as shown in the figure, R can be alkane, alkene, alkyne, alicyclic hydrocarbon, arene, oxazole, thiazole, thiophene, thiazine, pyrazole, imidazole, pyridine, and other different functional groups, as well as commonly used protecting groups including TIPS, TBS, Bn, Ac, Bz, Piv and Boc, etc.

[0009] Further, the catalyst is any one of the combination of CeBr3, FeBr3, FeBr2, and FeSO4-KBr, FeCl3-KBr, Fe(NO3)3-KBr, Ce(NO3)3-KBr, CeCl3-KBr, Ce(OTf)3-KBr, and other metals (Fe 2+ Fe 3+ Ce 3+ Ce

[0010] Further, the concentration of hydrogen peroxide used in the reaction is 3-30%, and the molar ratio of hydrogen peroxide to the starting compound is 3-6:1.

[0011] Further, the reaction is carried out in a solvent, and the solvent used is a mixed solvent composed of any one of ethanol, acetonitrile, tetrahydrofuran, and other water-miscible solvents and water.

[0012] Further, the preferred reaction time of the reaction is 0.5-2h.

[0013] Further, the processing method of the reaction is to quench with Na2S2O3 solution after the reaction is completed, and extract with an organic solvent (such as ethyl acetate, dichloromethane). Collect the organic phase, dry with anhydrous sodium sulfate, filter, and concentrate to obtain.

[0014] The present application has the following advantages:

[0015] The present application first realizes the synthesis and preparation of [1,2]thiazine derivatives with H2O2 as an oxidant. The [1,2]thiazine derivatives are synthesized by in-situ generation of RBS from MBrx-H2O2 under neutral conditions. The catalytic reaction is green and sustainable, and the byproduct is H2O, solving the problems of environmental damage and low yield caused by many other strong oxidant catalytic reactions. The present application avoids the use of expensive and complex catalysts, has mild reaction conditions, a simple reaction process, high yield, safety and environmental protection, conforms to the concept of green chemistry, has more extensive applicability, has broad development prospects and application prospects, and is expected to be widely used in the fields of organic synthesis, medicine, pesticides and probes. BRIEF DESCRIPTION OF DRAWINGS

[0016] Figure 1 and Figure 2 is the 1 H-NMR and 13 C-NMR spectrum

[0017] Figure 3 and Figure 4 is the 1 H-NMR and 13 C-NMR spectrum

[0018] Figure 5 and Figure 6 is the 1 H-NMR and 13 C-NMR spectrum

[0019] Figure 7 and Figure 8 is the 1 H-NMR and 13 C-NMR spectrum

[0020] Figure 9 and Figure 10 is the 1 H-NMR and 13 C-NMR spectrum

[0021] Figure 11 and Figure 12 is the 1 H-NMR and 13 C-NMR spectrum

[0022] Figure 13 and Figure 14 is the 1 H-NMR and 13 C-NMR spectrum

[0023] Figure 15 and Figure 16 is the1 H-NMR and 13 C-NMR spectra

[0024] Figure 17 and Figure 18 is the compound of Example 9 1 H-NMR and 13 C-NMR spectra

[0025] Figure 19 and Figure 20 is the compound of Example 10 1 H-NMR and 13 C-NMR spectra

[0026] Figure 21 and Figure 22 is the compound of Example 11 1 H-NMR and 13 C-NMR spectra

[0027] Figure 23 and Figure 24 is the compound of Example 12 1 H-NMR and 13 C-NMR spectra

[0028] Figure 25 and Figure 26 is the compound of Example 13 1 H-NMR and 13 C-NMR spectra

[0029] Figure 27 and Figure 28 is the compound of Example 14 1 H-NMR and 13 C-NMR spectra

[0030] Figure 29 and Figure 30 is the compound of Example 15 1 H-NMR and 13 C-NMR spectra DETAILED DESCRIPTION

[0031] The following examples are illustrative of the compounds of the present application: 1 H-NMR and 13 C-NMR spectra were measured at room temperature on a 400 MHz spectrometer, 1 H-NMR is 400 MHz, 13 C-NMR is 100 MHz, the spectrometer is from Bruker.

[0032] The application is illustrated in detail by the following examples, but the application is not limited to these examples:

[0033] Example 1

[0034]

[0035] To a stirred solution of 1a (1 g, 4.64 mmol) in EtOH / H2O (3 / 1) 23 mL, CeBr3(1.40 mmol, 0.26 g) and H2O2 aqueous solution (30%, 14.0 mmol, 1.4 mL) were added successively at room temperature. The reaction mixture was stirred for 0.5 h at room temperature. After completion of the reaction, the reaction mixture was quenched with Na2S2O3 solution (0.1 M) and extracted with ethyl acetate. The combined organic phase was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to afford the desired product 1b (yield: CeBr3: 91%). The compound was characterized by the following data: 1 H-NMR (400 MHz, CDC13) δ 7.95 (d, J = 8.1 Hz, 1H), 7.88 (dd, J = 7.9, 1.5 Hz, 1H), 7.58 (dt, J = 8.1, 4.4 Hz, 1H), 7.45 - 7.36 (m, 2H), 7.29 (ddd, J = 8.4, 7.0, 1.6 Hz, 1H), 7.21 (dd, J = 8.1, 1.4 Hz, 1H), 6.96 (ddd, J = 8.2, 7.0, 1.4 Hz, 1H), 2.33 (s, 3H). 13 C-NMR (101 MHz, CDC13) δ 149.0, 132.5, 131.7, 130.4, 127.5, 125.9, 124.7, 124.4, 124.1, 123.6, 120.7, 119.6, 32.1. HRMS (ESI + )(m / z) calcd for C 13 H 12 NS[M+H] + 214.0685; found 214.0690.

[0036] Example 2:

[0037]

[0038] EtOH / H20 (3 / 1) 17 mL, 2a (1 g, 3.40 mmol) were added successively into a round bottom flask, stirred homogeneously, then CeBr3(1.02 mmol, 0.38 g), H202 aqueous solution (30%, 10.2 mmol, 1.1 mL) were added successively into the mixture, stirred at room temperature for 3 h. After the reaction was completed, the reaction was quenched with Na2S203 solution (0.1 M), extracted with ethyl acetate. The organic phase was combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the target product 2b (yield: FeBr2: 53%; CeBr3: 58%). The characterization data of the compound are as follows: 1 H-NMR (400 MHz, CDC13) δ: 7.30-7.18 (m, 2H), 7.02 (td, J = 7.5, 1.0 Hz, 1H), 6.79 (d, J = 7.8 Hz, 1H), 3.48 (s, 2H), 3.18 (s, 3H). 13 C-NMR (100 MHz, CDC13) δ: 175.1, 145.2, 127.9, 124.5, 124.3, 122.4, 108.1, 35.8, 26.2. IR 3388.3, 3057.4, 1695.9, 1611.2, 1464.8, 1346.0, 1263.0, 1125.9, 1089.0, 753.7, 655.4 cm -1 ; HRMS (CI + )(m / z) calcd for C9H9NO [M] + 147.0679; found 147.0687.

[0039] Example 3:

[0040]

[0041] EtOH / H20 (3 / 1) 20 mL, 3a (1 g, 3.89 mmol) were added successively into a round bottom flask, stirred homogeneously, then CeBr3(1.17 mmol, 0.44 g), H202 aqueous solution (30%, 11.7 mmol, 1.2 mL) were added successively into the mixture, stirred at room temperature for 0.5 h. After the reaction was completed, the reaction was quenched with Na2S203 solution (0.1 M), extracted with ethyl acetate. The organic phase was combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the target product 3b (yield: CeBr3: 63%). The characterization data of the compound are as follows: 1H-NMR (400 MHz, CDC13) δ 7.86 (dd, J = 8.5, 2.1 Hz, 1H), 7.71 (d, J = 2.1 Hz, 1H), 7.44-7.35 (m, 1H), 7.29 (dd, J = 8.0, 1.2 Hz, 1H), 7.26-7.18 (m, 2H), 6.76 (d, J = 8.5 Hz, 1H), 4.04 (s, 2H), 2.50 (s, 3H), 2.38 (s, 3H). 13 C-NMR (101 MHz, CDC13) δ 196.5, 148.7, 138.8, 135.9, 132.2, 130.5, 130.2, 128.9, 127.8, 125.1, 124.9, 124.5, 114.4, 26.2, 15.3. HRMS (ESI + )(m / z) calcd for C 15 H 16 NOS [M + H] + 258.0947; found 258.0944.

[0042] Example 4:

[0043]

[0044] EtOH / H20 (3 / 1) 19 mL, 4a (1 g, 3.74 mmol) were added into a round bottom flask in turn, and then CeBr3(1.12 mmol, 0.43 g), H202 aqueous solution (30%, 11.2 mmol, 1.1 mL) were added into the mixture in turn, and the reaction was stirred at room temperature for 0.5 h. After the reaction was completed, the reaction was quenched with Na2S203 solution (0.1 M) and extracted with ethyl acetate. After the organic phases were combined, they were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the target product 4b (yield: CeBr3: 96%). The characterization data of the compound are as follows: 1 H-NMR (400 MHz, CDC13) δ 7.86 (dd, J = 8.5, 2.1 Hz, 1H), 7.71 (d, J = 2.1 Hz, 1H), 7.44-7.35 (m, 1H), 7.29 (dd, J = 8.0, 1.2 Hz, 1H), 7.26-7.18 (m, 2H), 6.76 (d, J = 8.5 Hz, 1H), 4.04 (s, 2H), 2.50 (s, 3H), 2.38 (s, 3H). 13 C-NMR (101 MHz, CDC13) δ 196.5, 148.7, 138.8, 135.9, 132.2, 130.5, 130.2, 128.9, 127.8, 125.1, 124.9, 124.5, 114.4, 26.2, 15.3. HRMS (ESI +)(m / z) calcd for C 15 H 12 N3S[M+H] + 266.0746; found 266.0737.

[0045] Example 5:

[0046]

[0047] EtOH / H2O (3 / 1) 19 mL, 5a (1 g, 4.16 mmol) were added into a round bottom flask successively, and stirred uniformly, then CeBr3(1.25 mmol, 0.47 g), H2O2 aqueous solution (30%, 12.5 mmol, 1.3 mL) were added into the mixture successively, and stirred at room temperature for 0.5 h. After the reaction was completed, the reaction was quenched with Na2S2O3 solution (0.1 M), and extracted with ethyl acetate. After the organic phases were combined, they were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the target product 5b (yield: CeBr3: 90%). The characterization data of the compound are as follows: 1 H-NMR (400 MHz, CDCI3) δ 8.05 (dd, J = 8.0, 1.5 Hz, 1 H), 7.94 (d, J = 8.1 Hz, 1 H), 7.64 (ddd, J = 8.1, 6.2, 2.6 Hz, 1 H), 7.59 (dd, J = 7.5, 1.5 Hz, 1 H), 7.54-7.45 (m, 2 H), 6.93 (t, J = 7.7 Hz, 1 H), 2.43 (s, 3 H). 13 C-NMR (101 MHz, CDCI3) δ 152.86, 135.14, 132.31, 131.40. 128.69, 128.20, 125.11, 124.67, 122.68, 121.17, 118.60, 118.53, 108.41, 33.29. HRMS (ESI + )(m / z) calcd for C 14 H 11 N2S[M+H] + 239.0637; found 239.0631.

[0048] Example 6:

[0049]

[0050] EtOH / H2O (3 / 1) 19 mL, 6a (1 g, 4.02 mmol) were added into a round bottom flask successively, stirred uniformly, then CeBr3(1.20 mmol, 0.46 g), H2O2 aqueous solution (30%, 12.0 mmol, 1.2 mL) were added into the mixture successively, stirred the reaction at room temperature for 0.5 h. After the reaction was completed, the reaction was quenched with Na2S2O3 solution (0.1 M), extracted with ethyl acetate. The organic phase was combined, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure to obtain the target product 6b (yield: CeBr3: 90%). The characterization data of the compound are as follows: 1 H-NMR (400 MHz, Chloroform-d) δ 7.78 (d, J = 8.0 Hz, 1H), 7.67-7.54 (m, 2H), 7.48-7.35 (m, 2H), 6.95 (ddd, J = 12.2, 7.7, 1.4 Hz, 1H), 2.32 (s, 3H). 13 C-NMR (100 MHz, CDC13) δ: 152.0 (dd, J = 250.3, 14.0 Hz), 146.6 (dd, J = 9.7, 1.8 Hz), 144.92 (dd, J = 239.2, 13.9 Hz), 132.0, 131.3, 128.0, 124.6, 124.4, 122.7, 116.6 (dd, J = 5.6, 2.7 Hz), 113.2 (d, J = 17.5 Hz), 111.9 (dd, J = 18.7, 2.1 Hz), 32.0. HRMS (ESI+) (m / z) calcd. for C 13 H 10 F2NS[M+H] + 250.0497; found 250.0505. IR 3018.5, 2920.1, 1717.3, 1556.7, 1482.1, 1396.0, 1261.2, 1173.0, 1131.0, 1067.9, 1031.9, 990.8, 929.9, 890.8, 850.6, 801.3 cm-1.

[0051] Example 7:

[0052]

[0053] EtOH / H2O (3 / 1) 19 mL, 7a (1 g, 4.11 mmol) were added into a round bottom flask successively, stirred uniformly, then CeBr3(1.23 mmol, 0.47 g), H2O2 aqueous solution (30%, 12.3 mmol, 1.3 mL) were added into the mixture successively, stirred the reaction at room temperature for 0.5 h. After the reaction was completed, the reaction was quenched with Na2S2O3 solution (0.1 M), extracted with ethyl acetate. After the organic phase was combined, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure to obtain the target product 7b (yield: CeBr3: 90%). The characterization data of the compound are as follows: 1 H-NMR (400 MHz, Chloroform-d) δ 7.39-7.33 (m, 1H), 7.28-7.24 (m, 1H), 7.23-7.18 (m, 2H), 6.81 (dd, J = 8.7, 2.9 Hz, 1H), 6.75 (d, J = 8.7 Hz, 1H), 6.66 (d, J = 2.8 Hz, 1H), 3.75 (s, 3H), 2.38 (s, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 152.6, 138.5, 137.2, 137.2, 130.3, 128.5, 127.2, 124.9, 124.6, 117.1, 115.6, 115.2, 55.7, 15.3. HRMS (ESI + )(m / z) calcd for C 14 H 16 NOS [M+H] + 246.0947; found 246.0944. IR 3441.6, 3352.2, 2987.2, 2920.5, 2825.4, 1595.1, 1500.0, 1461.2, 1425.1, 1323.9, 1274.6, 1243.4, 1207.9, 1170.3, 1083.9, 1036.4, 959.5, 878.7, 819.4 cm -1 .

[0054] Example 8:

[0055]

[0056] EtOH / H2O (3 / 1) 19 mL, 8a (1 g, 3.72 mmol) were added into a round bottom flask successively, stirred uniformly, then CeBr3(1.11 mmol, 0.42 g), H2O2 aqueous solution (30%, 11.1 mmol, 1.1 mL) were added into the mixture successively, stirred at room temperature for 0.5 h. After the reaction was completed, the reaction was quenched with Na2S2O3 solution (0.1 M), extracted with ethyl acetate. After the organic phase was combined, it was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the target product 8b (yield: CeBr3: 90%). The characterization data of the compound are as follows: 1 H-NMR (400 MHz, Chloroform-d) δ 7.97 (d, J = 8.0 Hz, 1H), 7.87 (t, J = 1.9 Hz, 1H), 7.59 (ddd, J = 8.1, 5.0, 1.9 Hz, 1H), 7.47 - 7.32 (m, 3H), 7.16 (d, J = 8.5 Hz, 1H), 2.35 (d, J = 1.4 Hz, 3H), 1.38 (d, J = 1.4 Hz, 9H). 13 C-NMR (101 MHz, Chloroform-d) δ 145.6, 142.5, 132.8, 131.7, 128.1, 127.3, 125.2, 124.6, 124.6, 123.6, 120.4, 120.0, 34.4, 32.0, 31.6. HRMS (ESI + )(m / z) calcd. for C17H20NS [M+H] + 270.1311; found 270.1303. IR 2957.0, 1666.3, 1597.5, 1475.6, 1433.8, 1398.0, 1362.1, 1257.6, 1142.4, 1034.1, 932.7, 866.6, 829.7 cm -1 .

[0057] Example 9:

[0058]

[0059] EtOH / H2O (3 / 1) 19 mL, 5a (1 g, 4.05 mmol) were added in a round bottom flask, stirred well, then CeBr3(1.21 mmol, 0.46 g), H2O2 aqueous solution (30%, 12.1 mmol, 1.2 mL) were added in the mixture successively, stirred at room temperature for 0.5 h. After the reaction was completed, the reaction was quenched with Na2S2O3 solution (0.1 M), extracted with ethyl acetate. After the organic phase was combined, anhydrous sodium sulfate was dried, filtered, concentrated under reduced pressure to obtain the target product 5b (yield: CeBr3: 90%). The characterization data of the compound are as follows: 1 H-NMR (400 MHz, DMSO-d6) δ 7.84 (d, J = 8.1 Hz, 1H), 7.62-7.50 (m, 1H), 7.48-7.36 (m, 3H), 7.01-6.90 (m, 1H), 2.37 (s, 3H), 2.27 (s, 3H). 13 C-NMR (100 MHz, CDCl3) δ: 152.0 (d, J = 175.5 Hz), 138.7, 131.2 (d, J = 7.6 Hz), 127.4 (d, J = 2.8 Hz), 126.9, 123.2, 120.3, 119.5, 119.1, 116.1 (d, J = 8.1 Hz), 113.8 (d, J = 22.3 Hz), 102.4 (d, J = 22.7 Hz), 27.1, 13.9. HRMS (ESI + )(m / z) calcd. for C 14 H 13 FNS[M+H] + 246.0747; found 246.0750.

[0060] Example 10:

[0061]

[0062] EtOH / H2O (3 / 1) 19 mL, 5a (1 g, 4.05 mmol) were added in a round bottom flask, stirred well, then CeBr3(1.21 mmol, 0.46 g), H2O2 aqueous solution (30%, 12.1 mmol, 1.2 mL) were added in the mixture successively, stirred at room temperature for 0.5 h. After the reaction was completed, the reaction was quenched with Na2S2O3 solution (0.1 M), extracted with ethyl acetate. After the organic phase was combined, anhydrous sodium sulfate was dried, filtered, concentrated under reduced pressure to obtain the target product 5b (yield: CeBr3: 90%). The characterization data of the compound are as follows: 1H-NMR (400 MHz, Chloroform-d) δ 7.90 (d, J = 8.1 Hz, 1H), 7.78 (d, J = 8.4 Hz, 1H), 7.59 (dp, J = 7.9, 2.9, 2.3 Hz, 1H), 7.51 - 7.34 (m, 2H), 7.19 (t, J = 1.8 Hz, 1H), 6.91 (dt, J = 8.4, 1.8 Hz, 1H), 2.35 (s, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 150.5, 136.0, 132.0, 127.8, 125.3, 125.2, 124.6, 124.5, 123.0, 119.8, 119.2, 32.3. HRMS (ESI + )(m / z) calcd for C 13 H 11 ClNS[M+H] + 248.0295; found 248.0289. IR 3045.8, 1580.5, 1529.2, 1457.4, 1379.7, 1260.1, 1210.4, 1130.1, 1080.4, 997.7, 954.7, 928., 866.9, 820.6 cm -1 .

[0063] Example 11:

[0064]

[0065] EtOH / H2O (3 / 1) 19 mL, 11a (1 g, 4.15 mmol) were added into a round bottom flask in turn, and then CeBr3(1.24 mmol, 0.47 g), H2O2 aqueous solution (30%, 12.4 mmol, 1.3 mL) were added into the mixture in turn, and the reaction was stirred at room temperature for 0.5 h. After the reaction was completed, the reaction was quenched with Na2S2O3 solution (0.1 M) and extracted with ethyl acetate. After the organic phases were combined, they were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the target product 11b (yield: CeBr3: 90%). The characterization data of the compound are as follows: 1 H-NMR (400 MHz, Chloroform-d) δ 7.94 (d, J = 8.1 Hz, 1H), 7.61 - 7.51 (m, 2H), 7.45 - 7.35 (m, 2H), 7.06 (s, 1H), 2.36 (s, 6H), 2.28 (s, 3H). 13C NMR (101 MHz, Chloroform-d) δ 144.8, 133.6, 132.8, 132.5, 131.4, 127.8, 127.2, 124.9, 124.2, 123.7, 122.1, 120.3, 31.8, 21.0, 18.6. HRMS (ESI + )(m / z) calcd for C 15 H 16 NS[M+H] + 242.0998; found 242.1006.

[0066] Example 12:

[0067]

[0068] EtOH / H2O (3 / 1) 19 mL, 12a (1 g, 4.40 mmol) were added into a round bottom flask successively, and stirred uniformly, then CeBr3(1.32 mmol, 0.50 g), H2O2 aqueous solution (30%, 13.2 mmol, 1.3 mL) were added into the mixture successively, and stirred at room temperature for 0.5 h. After the reaction was completed, the reaction was quenched with Na2S2O3 solution (0.1 M), and extracted with ethyl acetate. After the organic phases were combined, they were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the target product 12b (yield: CeBr3: 90%). The characterization data of the compound are as follows: 1 H-NMR (400 MHz, Chloroform-d) δ 7.94 (d, J = 8.0 Hz, 1H), 7.69 (s, 1H), 7.57 (dt, J = 8.8, 4.6 Hz, 1H), 7.40 (d, J = 4.4 Hz, 2H), 7.12 (s, 2H), 2.38 (s, 3H), 2.31 (d, J = 1.2 Hz, 3H). 13 C-NMR (101 MHz, Chloroform-d) δ 146.2, 132.4, 131.6, 131.5, 128.8, 127.4, 125.7, 124.6, 124.4, 124.3, 123.7, 120.6, 31.8, 21.0. HRMS (ESI + )(m / z) calcd for C 14 H 14 NS[M+H] + 228.0841; found 228.0849.

[0069] Example 13:

[0070]

[0071] EtOH / H2O (3 / 1) 19 ml, 13a (1 g, 4.11 mmol) were added in a round bottom flask, stirred well, then CeBr3(1.23 mmol, 0.47 g), H2O2 aqueous solution (30%, 12.3 mmol, 1.3 mL) were added in the mixture successively, stirred at room temperature for 0.5 h. After the reaction was completed, the reaction was quenched with Na2S2O3 solution (0.1 M), extracted with ethyl acetate. After the organic phase was combined, anhydrous sodium sulfate was dried, filtered, concentrated under reduced pressure to obtain the target product 13b (yield: CeBr3: 90%). The characterization data of the compound are as follows: 1 H-NMR (400 MHz, Chloroform-d) δ 7.35 (dt, J = 7.9, 4.4 Hz, 1H), 7.28-7.23 (m, 1H), 7.22-7.18 (m, 2H), 6.97 (d, J = 8.3 Hz, 1H), 6.42 (dd, J = 8.3, 2.5 Hz, 1H), 6.35 (d, J = 2.5 Hz, 1H), 3.80 (s, 3H), 2.38 (s, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 160.5, 145.0, 139.2, 136.9, 131.4, 130.8, 128.3, 124.8, 124.4, 118.9, 104.1, 101.0, 55.1, 15.2. HRMS (ESI + )(m / z) calcd for C 14 H 14 NOS [M+H] + 244.0791; found 244.0803.

[0072] Example 14:

[0073]

[0074] EtOH / H2O (3 / 1) 19 ml, 14a (1 g, 4.69 mmol) were added in a round bottom flask, stirred well, then CeBr3(1.23 mmol, 0.47 g), H2O2 aqueous solution (30%, 12.3 mmol, 1.3 mL) were added in the mixture successively, stirred at room temperature for 0.5 h. After the reaction was completed, the reaction was quenched with Na2S2O3 solution (0.1 M), extracted with ethyl acetate. After the organic phase was combined, anhydrous sodium sulfate was dried, filtered, concentrated under reduced pressure to obtain the target product 14b (yield: CeBr3: 90%). The characterization data of the compound are as follows: 1H-NMR (400 MHz, Chloroform-d) δ 8.62 (d, J = 2.0 Hz, 1H), 8.08-8.02 (m, 1H), 7.91 (dd, J = 8.6, 2.0 Hz, 1H), 7.62 (ddd, J = 8.3, 6.8, 2.0 Hz, 1H), 7.48-7.40 (m, 2H), 7.17 (d, J = 8.6 Hz, 1H), 3.91 (s, 3H), 2.37 (s, 3H). 13 C-NMR (101 MHz, Chloroform-d) δ 167.3, 154.4, 132.2, 132.2, 131.1, 128.1, 126.6, 125.5, 124.9, 124.7, 122.3, 120.6, 119.7, 51.8, 32.8. HRMS (ESI + )(m / z) calcd. for C 15 H 14 NO2S[M+H] + 272.0740; found 272.0736.

[0075] Example 15:

[0076]

[0077] EtOH / H2O (3 / 1) 19 mL, 15a (1 g, 4.33 mmol) were added into a round bottom flask in turn, and then CeBr3(1.30 mmol, 0.49 g), H2O2 aqueous solution (30%, 13.0 mmol, 1.3 mL) were added into the mixture in turn with stirring, and the reaction was stirred at room temperature for 0.5 h. After the reaction was completed, the reaction was quenched with Na2S2O3 solution (0.1 M) and extracted with ethyl acetate. After the organic phases were combined, they were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the target product 15b (yield: CeBr3: 90%). The characterization data of the compound are as follows: 1 H-NMR (700 MHz, CDCl3) δ 7.85 (d, J = 8.1 Hz, 1H), 7.84-7.78 (m, 1H), 7.55 (dt, J = 8.1, 4.3 Hz, 1H), 7.37 (d, J = 3.9 Hz, 2H), 6.85 (dd, J = 10.8, 2.7 Hz, 1H), 6.64 (ddd, J = 8.7, 8.1, 2.7 Hz, 1H), 2.31 (s, 3H). 13C-NMR(100MHz,CDCl3)δ:164.7(d,J=140.8Hz),151.1(d,J=6.7Hz),131.6,131.4,126.9,125.2(d,J=5.9Hz),124.0,123.7,122.0,116.6(d,J=1.4Hz),110.7,106.7,31.7.HRMS(ESI + )(m / z)calcd.for C 13 H 11 FNS[M+H] + 232.0591;found 248.0908.

Claims

1. A green synthesis process of [1,2]thiazine derivatives, characterized by, The thioether bond of a raw material compound is combined with an amino ring by using CeBr3 as a catalyst, hydrogen peroxide as an oxidant, and ethanol and water as solvents at room temperature and in an open condition, and the structure of the raw material compound is as follows:

2. The method of claim 1, wherein, The molar ratio of the raw material compound to the catalyst is 1:0.3-0.

6.

3. The method of claim 1, wherein, The oxidant is hydrogen peroxide with a concentration of 3-30%.

4. The method of claim 1, wherein, The molar ratio of the raw material compound to the oxidant is 1:3-5.

5. The method of claim 1, wherein, The solvent used in the reaction is ethanol:water 3:1, and the ratio of the solvent to the raw material compound is 5ml / 1mmol.

6. The method of claim 1, wherein, The reaction time is 0.5-2h.

7. The method of claim 1, wherein: After the reaction is completed, the target product is obtained by using a diluted Na2S2O3 solution 0.1M to quench, using ethyl acetate to extract for multiple times, filtering, and reducing pressure concentration.

Images