A method for one-step efficient green preparation of allyl thioacetamide

Abstract

The application belongs to the technical field of organic synthesis, and particularly relates to a method for efficiently and greenly preparing allyl ketoxime in one step. The preparation method specifically comprises the following steps: cross-coupling reaction of enol, hydrazine and aldehyde under the action of a palladium catalyst to obtain an allyl ketoxime compound. The reaction raw materials used in the application are cheap and easy to obtain. The allyl ketoxime compound can be efficiently and greenly prepared in one step through the coupling reaction, the synthesis process is simple, and the synthesis cost is greatly reduced. The reaction condition is mild, the yield is high, the substrate applicability range is wide, the reaction conversion efficiency is high, the gram-scale experiment can be realized, and industrialization is easy to realize.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of organic synthesis, and particularly relates to a method for efficiently and greenly preparing allyl hydrazone in one step. BACKGROUND

[0002] Allyl hydrazone compounds are an important class of compounds, which can be used as important intermediates for synthesizing imidazole, tetrazole, quinazolinone, quinoline, quinolone and other heterocyclic compounds due to the allyl hydrazone functional group contained in the structure. Acyl hydrazone compounds widely exist in various natural products and medical and agricultural chemical products, and usually exhibit special valuable physical and chemical properties and important biological activities. Therefore, the synthesis of the compounds, especially the development of a simple and environment-friendly synthesis path, is particularly important.

[0003] There are many synthesis methods for allyl hydrazone compounds. The early preparation methods are generally realized through multi-step reactions, and the reaction efficiency is low, the yield is low, a large amount of by-products is produced, and the operation is complex. In order to solve the problems caused by the reactions, an excess metal catalyst is introduced into the reaction system to catalytically prepare allyl hydrazone compounds in one step. Although good catalytic performance and substrate adaptability are achieved, complex raw materials and active reagents are still required, which not only requires harsh reaction conditions, but also greatly reduces the reaction efficiency, and a large amount of by-products is produced, which does not meet the basic requirements of green synthesis chemistry.

[0004] In order to solve such problems, a new synthesis method needs to be developed, that is, a metal catalyst is used to promote the direct reaction of cheap and easily available enol, hydrazine and aldehyde to greenly prepare allyl hydrazone compounds without adding external additives. So far, there is no related report on such reactions.

[0005] Therefore, it is an urgent problem to develop a green, rapid, practical and convenient synthesis method for allyl hydrazone. Directly using enol, hydrazine and aldehyde cross-coupling reaction, and preparing allyl hydrazone with wide substrate applicability under mild conditions has important theoretical significance and wide application prospect. SUMMARY

[0006] In view of the problems of the existing allyl hydrazone synthesis method, such as complicated reaction process, low reaction efficiency, low yield, a large amount of by-products produced, and complex operation, the application provides a method for efficiently and greenly preparing allyl hydrazone in one step.

[0007] In order to achieve the above purpose, the application adopts the following technical scheme:

[0008] The application discloses a one-step efficient green preparation method of allyl thioacetamide, which comprises the following steps: cross coupling reaction of enol, hydrazine and aldehyde under the action of a palladium catalyst to obtain an allyl thioacetamide compound, and a reaction route thereof is as follows:

[0009]

[0010] Wherein, R1 is selected from a fatty substituent group, a substituted aryl group or a furan group, R2 is selected from a fatty substituent group, a substituted aryl group or a naphthyl group, R3 is selected from a fatty substituent group, a substituted aryl group, a naphthyl group, a furan group or a thiophene group, and R' is selected from hydrogen or a fatty substituent group.

[0011] Further, the fatty substituent group in R1 is an alkyl group with 1-12 carbons, and the substituted aryl group is a methyl aryl group, a methoxy aryl group, a phenyl aryl group, a fluorine aryl group, a chlorine aryl group, a bromine aryl group or a trifluoromethyl aryl group.

[0012] Further, the fatty substituent group in R2 is a tert-butyl group, a cyclohexyl group or a substituted benzyl group, and the substituted aryl group is a methyl aryl group, a phenyl aryl group, a fluorine aryl group, a chlorine aryl group, a bromine aryl group, a trifluoromethyl aryl group or a trifluoromethoxy aryl group.

[0013] Further, the fatty substituent group in R3 is a benzyl group or an alkyl group with 1-12 carbons, and the substituted aryl group is a methyl aryl group, a tert-butyl aryl group, a methoxy aryl group, a phenyl aryl group, a biphenyl aryl group, a fluorine aryl group, a chlorine aryl group, a trifluoromethyl aryl group, a trifluoromethoxy aryl group, a hydroxyl aryl group, a nitro aryl group or an N,N-dimethyl aryl group.

[0014] Further, the fatty substituent group in R' is an alkyl group with 1-12 carbons.

[0015] Further, the palladium catalyst is one or more of PdCl2, PdBr2, PdI2, Pd(OAc)2, Pd(TFA)2, PdCl2(CH3CN)2, PdBr2(CH3CN)2, PdCl2(COD), PdBr2(COD), PdCl2(PhCN)2, [PdCl(CH2=CHCH2)]2, [PdCl(PhCH2=CHCH2)]2, PdCl2(Xantphos), PdCl2(Ph3P )2 , PdCl2[P(3,5-F2Ph)3]2.

[0016] Furthermore, when the palladium catalyst is one or more of PdCl2, PdBr2, PdI2, Pd(OAc)2, Pd(TFA)2, PdCl2(CH3CN)2, PdBr2(CH3CN)2, PdCl2(COD), PdBr2(COD), PdCl2(PhCN)2, [PdCl(CH2=CHCH2)]2, and [PdCl(PhCH2=CHCH2)]2, the preparation method of allyl hydrazone further includes adding a coagulant. The ligand is one or more of PPh2(3,5-Me2Ph), P(3-FPh)3, P(2-FPh)3, P(3,5-F2Ph)3, P(3,5-Me2Ph)3, P(3,5-(MeO)2Ph)3, P(3,5-(CF3)2Ph)3, Xantphos, NiXantphos, Sixantphos, Xant(o-tolyl)phos, DPEphos, and BIANP.

[0017] Furthermore, the amount of the catalyst used is 0.1-10% of the molar amount of hydrazine.

[0018] Further, the solvent is any one of 1,4-dioxane, anisole, dimethyl ether, ethyl acetate, acetonitrile, toluene, xylene, mesitylene, tetrahydrofuran, dichloromethane, dichloroethane, or chloroform. Dichloromethane or anisole is preferred.

[0019] Furthermore, the coupling reaction temperature is 25-130℃, and the time is 3-24 hours.

[0020] Compared with the prior art, the present invention has the following advantages:

[0021] 1. The reactants used in this invention are inexpensive and readily available. Through coupling reaction, allylhydrazone compounds can be prepared efficiently and in a green manner in just one step. The synthesis process is simple and greatly reduces the synthesis cost.

[0022] 2. This invention enables the efficient synthesis of various substituted allyl hydrazone compounds;

[0023] 3. The present invention has mild reaction conditions, high yield, and a wide range of substrate applicability;

[0024] 4. The raw materials used in this invention are clean and non-toxic, causing minimal environmental pollution and exhibiting high atom economy;

[0025] 5. The reaction process of this invention is clean and simple to operate, which better meets the requirements of green chemistry;

[0026] 6. The reaction has high conversion efficiency, can be carried out on a gram-scale scale, and is easy to industrialize. Detailed Implementation

[0027] For the purposes of promoting an understanding of the principles of the application, reference will be made to the embodiment illustrated in the drawings. It is understood that specific embodiments described herein are shown by way of illustration and not as limitations. Although particular embodiments of the application have been disclosed in detail herein for purposes of illustrating the applicability of the present application, it will be understood by those skilled in the art that various changes in form and details of the application can be made without departing from the spirit and scope of the application. It is therefore intended that the application not be limited to the particular embodiment disclosed as the best mode contemplated for carrying out the present application, but that the application include all embodiments falling within the scope of the appended claims.

[0028] Preparation of allyl hydrazone D1

[0029] The synthetic route is as follows:

[0030]

[0031] Example 1

[0032] In a glove box, a dry pressure tube with magnetic stirring was charged with allyl alcohol A1 (0.75 mmol), phenylhydrazine B1 (0.5 mmol), benzaldehyde C1 (0.7 mmol), PdCl2(Xantphos) (0.01 mmol, 2 mol%) and toluene (2.0 mL). The pressure tube was sealed with a polytetrafluoroethylene cap and placed in a preheated metal bath at 60 °C for 4 h. The reaction was stopped and the product was purified by column chromatography with a yield of 95%.

[0033] 1 H NMR (400 MHz, CDC13) δ 7.72 - 7.65 (m, 2H), 7.57 - 7.16 (m, 13H), 6.95 (t, J = 7.2 Hz, 1H), 6.52 - 6.40 (m, 1H), 6.31 - 6.22 (m, 1H), 4.71 (dd, J = 4.0, 2.0 Hz, 2H).13C NMR (101 MHz, CDC13) δ 147.6, 136.6, 136.3, 132.4, 131.3, 129.1, 128.6, 128.6, 127.9, 127.7, 126.4, 126.2, 121.7, 120.7, 114.9, 48.5. HRMS (ESI) calcd. for C22H21N2 [M+H]: 313.1699, found: 313.1695.

[0034] Examples 2-8

[0035] Different from Example 1: the catalyst was replaced by PdCl2[CH3CN]2, and a ligand (monodentate ligand, 0.021 mmol, 4.2 mol%; bidentate ligand, 0.012 mmol, 2.2 mol%) was added. The specific data are shown in the following table:

[0036]

[0037]

[0038] Examples 9-13

[0039] The difference from Example 4 is the kind of catalyst. The specific data are shown in the following table.

[0040]

[0041] Examples 14-17

[0042] The difference from Example 1 is the amount of PdCl2(Xantphos). The specific data are shown in the following table.

[0043]

[0044]

[0045] Examples 18-21

[0046] The difference from Example 1 is the amount of toluene. The specific data are shown in the following table.

[0047]

[0048] Examples 22-27

[0049] The difference from Example 1 is the kind of solvent. The specific data are shown in the following table.

[0050]

[0051] Examples 28-33

[0052] The difference from Example 1 is the amount of allyl alcohol Al. The specific data are shown in the following table.

[0053]

[0054]

[0055] Examples 34-38

[0056] The difference from Example 1 is the amount of phenylhydrazine Bl. The specific data are shown in the following table.

[0057]

[0058] Examples 39-43

[0059] The difference from Example 1 is the amount of benzaldehyde Cl. The specific data are shown in the following table.

[0060]

[0061] Examples 44-47

[0062] The difference from Example 1 is: reaction time. The specific data are shown in the following table:

[0063]

[0064]

[0065] Examples 48-51

[0066] The difference from Example 1 is: reaction temperature. The specific data are shown in the following table:

[0067]

[0068] Examples 52-56

[0069] The difference from Example 1 is: reaction atmosphere. The specific data are shown in the following table:

[0070]

[0071] Preparation of allyl thioacetate D2-D29

[0072] Examples 57-84

[0073] The difference from Example 1 is: C1 is replaced by C2, C3, …, C29. The specific data are shown as follows:

[0074]

[0075]

[0076] D2 yield 94%: 1 H NMR (400 MHz, CDC13) δ 7.57 (d, J = 8.2 Hz, 2H), 7.45 (s,

[0077] 1H), 7.43 - 7.36 (m, 2H), 7.35 - 7.27 (m, 4H), 7.23 (t, J = 7.4 Hz, 2H), 7.16 (m, 3H), 6.92 (t, J = 7.2 Hz, 1H), 6.42 (m, 1H), 6.21 (m, 1H), 4.61 (m, 2H), 2.32 (s, 3H). 13C NMR (101 MHz, CDC13) δ 147.8, 137.9, 136.5, 134.0, 132.7, 131.3, 129.4, 129.2, 128.7, 127.8, 126.5, 126.3, 122.0, 120.6, 114.9, 48.5, 21.5. HRMS (ESI) calcd. for C 23 H 22 N2[M+H]: 327.1855, found: 327.1853.

[0078] D3 yield 93%: 1 H NMR (400 MHz, CDC13) δ 7.53 - 7.38 (m, 5H), 7.36 - 7.26 (m, 4H), 7.22 (td, J = 7.3, 3.7 Hz, 3H), 7.19 - 7.13 (m, 1H), 7.04 (d, J = 7.5 Hz, 1H), 6.93 (m, 1H), 6.44 - 6.35 (m, 1H), 6.20 (m, 1H), 4.61 (m, 2H), 2.34 (s, 3H). 13 C NMR (101 MHz, CDC13) δ 175.6, 147.9, 147.2, 142.9, 142.1, 136.3, 130.2, 129.2, 129.2, 128.7, 127.6, 126.8, 126.6, 122.5, 114.6, 108.1, 56.0, 43.3, 19.7. HRMS (ESI) calcd. for C 23 H 22 N2[M+H]: 327.1855, found: 327.1858.

[0079] D4 yield 91%: 1 H NMR (400 MHz, CDC13) δ 7.91 (d, J = 7.7 Hz, 1H), 7.70 (s,

[0080] 1H), 7.46 - 7.07 (m, 11H), 6.93 (m, 1H), 6.50 - 6.40 (m, 2H), 6.20 (m, 1H), 4.65 (m, 2H), 2.40 (d, J = 1.3 Hz, 3H). 13C NMR (101 MHz, CDC13) δ 147.8, 136.5, 135.4, 134.6, 131.8, 131.6, 130.8, 129.3, 128.7, 127.8, 127.8, 126.5, 126.3, 126.0, 121.7, 120.8, 115.0, 48.6, 20.2. HRMS (ESI) calcd. for C 23 H 22 N2[M+H]: 327.1855, found: 327.1857.

[0081] D5 yield 73%: 1 H NMR (400 MHz, CDC13) δ 7.74 (s, 1H), 7.38 - 7.13 (m, 9H), 6.94 - 6.82 (m, 3H), 6.46 (m, 1H), 6.22 (m, 1H), 4.67 (m, 2H), 2.43 (s, 6H), 2.25 (s, 3H). 13 C NMR (101 MHz, CDC13) δ 147.9, 137.1, 136.6, 136.5, 133.3, 131.7, 130.3, 129.6, 129.3, 128.7, 127.8, 126.4, 121.7, 120.4, 114.6, 48.2, 21.9, 21.2. HRMS (ESI) calcd. for C 25 H 26 N2[M+H]: 355.2168, found: 355.2162.

[0082] D6 yield 81%: 1 H NMR (400 MHz, CDC13) δ 7.66 - 7.57 (m, 2H), 7.49 - 7.11 (m, 13H), 6.95 - 6.86 (m, 1H), 6.40 (m, 1H), 6.28 - 6.14 (m, 1H), 4.60 (s, 1H), 1.37 - 1.19 (m, 9H). 13 C NMR (101 MHz, CDC13) δ 151.2, 147.8, 136.5, 134.1, 132.6, 131.3, 129.3, 128.7, 127.8, 126.5, 126.1, 125.7, 121.9, 120.6, 114.9, 48.5, 34.8, 31.5. HRMS (ESI) calcd. for C 26 H 28 N2[M+H]: 369.2325, found: 369.2330.

[0083] D7 yield 96%: 1 H NMR (400 MHz, CDC13) δ 7.72 (m, 2H), 7.63 - 7.09 (m, 17H), 6.94 (t, J = 7.3 Hz, 1H), 6.40 (d, J = 16.1 Hz, 1H), 6.17 (m, 1H), 4.68 - 4.47 (m, 2H). 13 C NMR (101 MHz, CDC13) δ 147.7, 140.9, 140.6, 136.5, 135.9, 132.2, 131.5, 129.4, 129.0, 128.8, 127.9, 127.5, 127.4, 127.1, 126.8, 126.6, 121.9, 121.0, 115.1, 48.5. HRMS (ESI) calcd. for C 28 H 24 N2[M+H]: 389.2012, found: 389.2013.

[0084] D8 yield 88%: 1 H NMR (400 MHz, CDC13) δ 7.64 - 7.57 (m, 2H), 7.45 - 7.10 (m, 10H), 6.95 - 6.82 (m, 3H), 6.44 - 6.35 (m, 1H), 6.18 (m, 1H), 4.56 (m, 2H), 3.72 (s, 3H). 13 C NMR (101 MHz, CDC13) δ 159.8, 147.8, 136.6, 132.5, 131.3, 129.7, 129.3, 128.7, 127.8, 127.7, 126.5, 122.2, 120.5, 114.8, 114.2, 55.4, 48.5. HRMS (ESI) calcd. for C 23 H 22 N2O[M+H]: 343.1805, found: 343.1804.

[0085] D9 yield 85%: 1 H NMR (400 MHz, CDC13) δ 7.45 - 7.38 (m, 3H), 7.37 - 7.12 (m, 10H), 6.94 (m, 1H), 6.84 - 6.76 (m, 1H), 6.42 (m, 1H), 6.21 (m, 1H), 4.63 (m, 2H), 3.81 (s, 3H). 13C NMR (101 MHz, CDC13) δ 156.0, 147.6, 138.2, 136.4, 132.3, 131.4, 129.7, 129.3, 128.7, 127.8, 126.5, 121.7, 120.9, 119.4, 115.0, 114.0, 110.8, 55.4, 48.6. HRMS (ESI) calcd. for C 23 H 22 N2O [M+H]: 343.1805, found: 343.1805.

[0086] D10 yield 81%: 1 H NMR (400 MHz, CDC13) δ 8.07 (dd, J = 7.8, 1.8 Hz, 1H),

[0087] 7.90 (s, 1H), 7.46 - 7.36 (m, 2H), 7.35 - 7.09 (m, 8H), 7.01 - 6.84 (m, 2H), 6.79 (m, 1H), 6.43 (d, J = 16.1 Hz, 1H), 6.19 (m, 1H), 4.62 (m, 2H), 3.72 (s, 3H). 13 C NMR (101 MHz, CDC13) δ 157.1, 147.9, 136.7, 131.5, 129.3, 129.1, 128.7, 128.5, 127.7, 126.6, 125.6, 125.4, 122.1, 121.0, 120.6, 114.9, 111.2, 55.7, 48.4. HRMS (ESI) calcd. for C 23 H 22 N2O [M+H]: 343.1805, found: 343.1800.

[0088] D11 yield 92%: 1 H NMR (400 MHz, CDC13) δ 7.64 (dd, J = 8.7, 5.5 Hz, 2H),

[0089] 7.48 - 7.16 (m, 10H), 7.08 - 6.88 (m, 3H), 6.49 - 6.37 (m, 1H), 6.25 (m, 1H), 4.67 (m, 2H). 13C NMR (101 MHz, CDC13) δ 163.8, 161.4, 147.6, 136.4, 132.9, 131.4, 131.3, 129.2, 128.6, 127.8, 127.8, 127.7, 126.4, 121.7, 120.8, 115.7, 115.5, 114.9, 48.6. HRMS (ESI) calcd. for C 22 H 19 FN2 [M+H]: 331.1605, found: 331.1600.

[0090] D12 yield 90%: 1 H NMR (400 MHz, CDC13) δ 7.48 - 7.09 (m, 13 H), 7.00 - 6.83 (m, 2 H), 6.41 (d, J = 16.1 Hz, 1 H), 6.20 (m, 1 H), 4.62 (m, 2 H). 13 C NMR (101 MHz, CDC13) δ 164.5, 162.1, 147.5, 139.2, 139.2, 136.3, 131.5, 131.0, 130.2, 130.1, 129.3, 128.7, 128.0, 126.5, 122.4, 121.5, 121.2, 115.2, 114.8, 114.6, 112.3, 112.1, 48.6. HRMS (ESI) calcd. for C 22 H 19 FN2 [M+H]: 331.1605, found: 331.1605.

[0091] D13 yield 87%: 1 H NMR (400 MHz, CDC13) δ 8.05 (m, 1 H), 7.70 (s, 1 H), 7.48 - 7.07 (m, 11 H), 7.06 - 6.90 (m, 2 H), 6.46 (m, 1 H), 6.23 (m, 1 H), 4.69 (m, 2 H). 13 C NMR (101 MHz, CDC13) δ 161.9, 159.4, 147.5, 136.4, 131.7, 129.2, 129.2, 129.0, 128.9, 128.6, 127.8, 126.5, 125.9, 125.3, 124.5, 124.4, 124.3, 124.2, 121.3, 121.1, 115.7, 115.5, 115.1, 48.5. HRMS (ESI) calcd. for C 22 H 19FN2 [M+H]: 331.1605, found: 313.1605.

[0092] D14 yield 90%: 1 H NMR (400 MHz, CDC13) δ 7.55 (d, J = 8.6 Hz, 2H), 7.43 - 7.36 (m, 6H), 7.34 - 7.28 (m, 2H), 7.27 - 7.21 (m, 2H), 7.21 - 7.15 (m, 2H), 7.15 - 7.09 (m, 2H), 7.09 - 7.03 (m, 2H), 6.97 (t, J = 7.3 Hz, 1H), 6.45 (d, J = 16.0 Hz, 1H), 6.15 (m, 1H), 4.62 (m, 2H).

[0093] 7.11 (m, 12H), 6.93 (t, J = 7.2 Hz, 1H), 6.43 - 6.33 (m, 1H), 6.15 (m, 1H), 4.56 (m, 2H). 13 C NMR (101 MHz, CDC13) δ 147.6, 136.4, 135.4, 133.4, 131.5, 131.1, 129.4, 128.9, 128.8, 128.8, 128.0, 127.5, 126.6, 121.7, 121.2, 115.1, 48.6. HRMS (ESI) calcd. for C 22 H 19 ClN2 [M+H]: 347.1309, found: 347.1313.

[0094] D15 yield 85%: 1 H NMR (400 MHz, CDC13) δ 8.08 (m, 1H), 7.87 (s, 1H), 7.48 - 7.03 (m, 12H), 6.95 (t, J = 7.3 Hz, 1H), 6.47 (d, J = 16.0 Hz, 1H), 6.16 (m, 1H), 4.63 (m, 2H). 13 C NMR (101 MHz, CDC13) δ 147.5, 136.5, 134.0, 133.0, 132.3, 129.8, 129.4, 129.3, 128.7, 127.9, 127.0, 126.6, 126.5, 121.4, 121.3, 115.3, 48.8.

[0095] D16 yield 86%: 1 H NMR (400 MHz, CDC13) δ 7.72 (d, J = 8.2 Hz, 2H), 7.55 (d,

[0096] J = 8.2 Hz, 2H), 7.47 - 7.14 (m, 10H), 7.02 - 6.91 (m, 1H), 6.41 (m, 1H), 6.19 (m, 1H), 4.62 (m, 2H). 13C NMR (101 MHz, CDC13) δ 147.4, 140.2, 136.3, 131.6, 130.5, 129.4, 129.4, 128.7, 128.0, 126.5, 126.2, 125.7, 125.6, 125.5, 121.6, 121.3, 115.4, 48.7. HRMS (ESI) calcd. for C 23 H 19 F3N2[M+H]: 381.1573, found: 381.1576.

[0097] D17 yield 86%: 1 H NMR (400 MHz, CDC13) δ 8.23 - 8.07 (m, 2H), 7.84 - 7.65 (m, 2H), 7.51 - 7.13 (m, 10H), 7.02 (t, J = 7.2 Hz, 1H), 6.49 - 6.36 (m, 1H), 6.23 (m, 1H), 4.70 (m, 2H). 13 C NMR (101 MHz, CDC13) δ 147.0, 146.6, 143.1, 136.1, 131.8, 129.4, 129.4, 128.7, 128.1, 126.5, 126.3, 124.1, 122.1, 120.9, 115.7, 49.0. HRMS (ESI) calcd. for C 22 H 19 N3O2[M+H]: 358.1550, found: 358.1546.

[0098] D18 yield 65%: 1 H NMR (400 MHz, CDC13) δ 11.45 (s, 1H), 7.62 (s, 1H), 7.43 - 7.09 (m, 11H), 7.04 - 6.95 (m, 2H), 6.85 (m, H), 6.48 (m, 1H), 6.24 (m, 1H), 4.67 (m, 2H). 13 C NMR (101 MHz, CDC13) δ 156.8, 146.7, 137.3, 136.1, 131.9, 129.7, 129.6, 129.5, 128.7, 128.0, 126.5, 121.9, 121.2, 119.5, 119.4, 116.6, 115.4, 49.3. HRMS (ESI) calcd. for C 22 H 20 N2O [M+H]: 329.1648, found: 329.1651.

[0099] D19 yield 63%: 1 H NMR (400 MHz, CDC13) δ 7.62 - 7.54 (m, 2H), 7.48 (s, 1H), 7.44 - 7.15 (m, 9H), 6.89 (m, 1H), 6.77 - 6.64 (m, 2H), 6.46 (m, 1H), 6.28 (m, 1H), 4.66 (m, 2H), 2.97 (s, 6H). 13 C NMR (101 MHz, CDC13) δ 147.9, 136.6, 133.6, 131.1, 129.1, 128.6, 127.6, 127.4, 126.4, 122.4, 119.8, 114.4, 112.3, 48.5, 40.5. HRMS (ESI) calcd. for C 24 H 25 N3[M+H]: 356.2121, found: 356.2121.

[0100] D20 yield 85%: 1 H NMR (400 MHz, CDC13) δ 7.64 (dd, J = 8.9, 2.5 Hz, 2H),

[0101] 7.54 - 7.11 (m, 12H), 6.95 (t, J = 7.1 Hz, 1H), 6.39 (dd, J = 16.1, 2.3 Hz, 1H), 6.17 (m, 1H), 4.58 (t, J = 2.9 Hz, 2H). 13 C NMR (101 MHz, CDC13) δ 148.8, 148.7, 147.6, 136.4, 135.6, 131.5, 130.8, 129.4, 128.8, 128.0, 127.4, 126.5, 121.5, 121.3, 121.2, 115.2, 48.61. HRMS (ESI) calcd. for C 23 H 19 F3N2O [M+H]: 397.1522, found: 397.1522.

[0102] D21 yield 83%: 1 H NMR (400 MHz, CDC13) δ 8.64 - 8.51 (m, 1H), 8.19 (s, 1H), 7.97 (m, 1H), 7.89 - 7.71 (m, 2H), 7.58 - 7.15 (m, 12H), 7.02 - 6.93 (m, 1H), 6.61 - 6.49 (m, 1H), 6.31 (m, 1H), 4.78 (m, 2H). 13C NMR (101 MHz, CDC13) δ 147.7, 136.4, 134.1, 132.1, 131.8, 131.6, 130.7, 129.3, 128.8, 128.7, 128.4, 127.8, 126.5, 126.4, 125.8, 125.7, 125.2, 124.0, 121.8, 120.9, 115.1, 48.7. HRMS (ESI) calcd. for C 26 H 22 N2[M+H]: 363.1855, found: 363.1855.

[0103] D22 yield 44%: 1 H NMR (400 MHz, CDC13) δ 8.09 (m, 1H), 7.90 - 7.75 (m, 4H), 7.67 (s, 1H), 7.53 - 7.12 (m, 11H), 7.03 - 6.93 (m, 1H), 6.55 - 6.45 (m, 1H), 6.31 (m, 1H), 4.76 (m, 2H). 13 C NMR (101 MHz, CDC13) δ 147.7, 136.4, 134.1, 132.1, 131.8, 131.6, 130.7, 129.3, 128.8, 128.7, 128.4, 127.8, 126.5, 126.4, 125.8, 125.7, 125.2, 124.0, 121.8, 120.9, 115.1, 48.7. HRMS (ESI) calcd. for C 26 H 22 N2[M+H]: 363.1855, found: 363.1852.

[0104] D23 yield 87%, 1 H NMR (400 MHz, CDC13) δ 7.44 - 7.12 (m, 11H), 6.93 (t, J = 7.1 Hz, 1H), 6.49 (d, J = 3.4 Hz, 1H), 6.45 - 6.34 (m, 2H), 6.18 (m, 1H), 4.59 (m, 2H).

[0105] 7.1Hz, 1H), 6.49 (d, J = 3.4 Hz, 1H), 6.45 - 6.34 (m, 2H), 6.18 (m, 1H), 4.59 (m, 2H). 13 C NMR (101 MHz, CDC13) δ 147.7, 136.4, 134.1, 132.1, 131.8, 131.6, 130.7, 129.3, 128.8, 128.7, 128.4, 127.8, 126.5, 126.4, 125.8, 125.7, 125.2, 124.0, 121.8, 120.9, 115.1, 48.7. HRMS (ESI) calcd. for C 20 H18 N2O [M+H]: 303.1491, found: 303.1488.

[0106] D24 yield 84%, 1 H NMR (400 MHz, CDC13) δ 7.65 (s, 1H), 7.50 - 7.13 (m, 10H), 7.07 - 6.87 (m, 3H), 6.44 (m, 1H), 6.22 (m, 1H), 4.62 (m, 2H). 13 C NMR (101 MHz, CDC13) δ 147.3, 142.5, 136.4, 131.4, 129.2, 128.7, 127.8, 127.6, 127.3, 126.5, 125.9, 125.1, 121.6, 120.9, 114.9, 48.8. HRMS (ESI) calcd. for C 20 H 18 N2S [M+H]: 319.1263, found: 319.1258.

[0107] D25 yield 88%, 1 H NMR (400 MHz, CDC13) δ 7.34 - 7.22 (m, 8H), 7.22 - 7.15 (m, 1H), 6.90 - 6.77 (m, 2H), 6.36 (m, 1H), 6.14 (m, 1H), 4.48 (m, 2H), 2.33 (m, 2H), 1.59 - 1.46 (m, 2H), 1.36 (h, J = 7.2 Hz, 2H), 0.90 (t, J = 7.3 Hz, 3H). 13 C NMR (101 MHz, CDC13) δ 148.1, 136.9, 136.7, 131.1, 129.1, 128.6, 128.6, 127.6, 126.5, 126.4, 122.6, 119.8, 114.3, 48.5, 32.8, 29.7, 22.4, 14.1. HRMS (ESI) calcd. for C 21 H 24 N2 [M+H]: 307.2168, found: 307.1799.

[0108] D26 yield 89%, 1 H NMR (400 MHz, CDC13) δ 7.48 - 7.05 (m, 14H), 6.86 (m, 2H), 6.33 (m, 1H), 6.12 - 5.97 (m, 1H), 4.42 (m, 2H), 3.65 (m, 2H). 13C NMR (101 MHz, CDC13) δ 148.0, 138.7, 136.7, 134.8, 131.4, 129.3, 129.3, 129.1, 129.1, 128.8, 128.7, 127.8, 126.6, 126.5, 122., 120.3, 114.7, 48.5, 39.7. HRMS (ESI) calcd. for C 23 H 22 N2[M+H]: 327.1855, found: 327.1853.

[0109] D27 yield 81%, 1 H NMR (400 MHz, CDC13) δ 7.48 - 7.07 (m, 12 H), 6.89 (m, 1 H), 6.48 - 6.24 (m, 2 H), 6.17 (m, 1 H), 5.84 (m, 1 H), 4.59 - 4.49 (m, 2 H), 1.82 (m, 3 H). 13 C NMR (101 MHz, CDC13) δ 147.6, 136.5, 135.8, 131.7, 131.2, 130.4, 129.2, 128.7, 127.8, 127.7, 126.5, 122.2, 120.4, 115.0, 114.7, 48.5, 18.5. HRMS (ESI) calcd. for C 19 H 22 N2[M-H]: 277.1699, found: 277.1697.

[0110] D28 yield 80%, 1 H NMR (400 MHz, CDC13) δ 7.42 - 7.10 (m, 9 H), 6.92 - 6.75 (m, 2 H), 6.36 (m, 1 H), 6.14 (m, 1 H), 5.13 - 4.97 (m, 1 H), 4.48 (m, 2 H), 2.34 (m, 1 H), 2.20 (m, 1 H), 1.98 (m, 2 H), 1.79 - 1.62 (m, 4 H), 1.57 (s, 2 H), 1.46 - 1.12 (m, 3 H), 0.92 (d, J = 6.7 Hz, 3 H). 13 C NMR (101 MHz, CDC13) δ 148.1, 136.6, 135.9, 131.3, 131.1, 129.1, 128.6, 127.6, 126.4, 124.8, 122.4, 119.8, 114.4, 48.5, 40.2, 36.9, 31.8, 25.9, 25.6, 19.7, 17.8. HRMS (ESI) calcd. for C25 H 32 N2[M+H]: 361.2638, found: 361.2638.

[0111] D29 yield 92%, 1 H NMR (400 MHz, CDC13) δ 8.35 - 8.29 (m, 1H), 8.12 (m, 1H), 7.96 - 7.88 (m, 1H), 7.73 (s, 1H), 7.51 - 7.41 (m, 3H), 7.41 - 7.32 (m, 6H), 7.32 - 7.15 (m, 4H), 6.94 (m, 1H), 6.56 - 6.46 (m, 1H), 6.31 (m, 1H), 4.72 (m, 2H), 4.32 (q, J = 7.2 Hz, 2H), 1.40 (t, J = 7.2 Hz, 3H). 13 C NMR (101 MHz, CDC13) δ 147.9, 140.4, 140.0, 136.5, 134.2, 131.3, 129.2, 128.6, 127.9, 127.7, 126.5, 125.8, 124.1, 123.2, 123.1, 122.3, 120.6, 120.2, 119.1, 118.9, 114.7, 108.7, 48.7, 37.7, 13.9. HRMS (ESI) calcd. for C 30 H 27 N3[M+H]: 430.2278, found: 430.2276.

[0112] Preparation of allyl hydrazones D30-D47

[0113] Examples 85-102

[0114] Different from Example 1: B1 is replaced by B2, B3...B20. The specific data are shown as follows:

[0115]

[0116]

[0117] D30 yield 89%: 1 H NMR (400 MHz, CDC13) δ 7.70 - 7.61 (m, 2H), 7.40 (s, 1H), 7.35 - 7.07 (m, 12H), 6.39 (m, 1H), 6.16 (m, 1H), 4.55 (m, 2H), 2.28 (s, 3H). 13C NMR (101 MHz, CDC13) δ 145.7, 137.0, 136.6, 132.0, 131.4, 130.3, 129.9, 128.8, 127.9, 127.9, 126.6, 126.3, 122.1, 115.3, 48.8, 20.8. HRMS (ESI) calcd. for C 23 H 23 N2[M+H]: 327.1855, found: 327.1856.

[0118] D31 yield 85%: 1 H NMR (400 MHz, CDC13) δ 7.74 - 7.60 (m, 2H), 7.45 (s, 1H), 7.40 - 7.08 (m, 11H), 6.77 (m, 1H), 6.42 (m, 1H), 6.22 (m, 1H), 4.63 (m, 2H), 2.37 (s, 3H). 13 C NMR (101 MHz, CDC13) δ 147.8, 139.0, 136.8, 136.5, 132.4, 131.4, 129.1, 128.7, 128.7, 127.9, 127.8, 126.5, 126.3, 122.0, 121.8, 115.7, 112.3, 48.7, 22.0. HRMS (ESI) calcd. for C 23 H 23 N2[M+H]: 327.1855, found: 327.1856.

[0119] D32 yield 82%: 1 H NMR (400 MHz, CDC13) δ 7.57 - 7.46 (m, 2H), 7.44 - 7.02 (m, 13H), 6.59 - 6.47 (m, 1H), 6.36 (m, 1H), 4.44 (m, 2H), 2.27 (s, 3H). 13 C NMR (101 MHz, CDC13) δ 145.1, 137.1, 136.9, 135.4, 133.4, 132.3, 131.3, 128.7, 128.6, 127.7, 127.6, 127.3, 126.7, 126.5, 126.3, 125.8, 125.6, 57.7, 18.8. HRMS (ESI) calcd. for C 23 H 23 N2[M+H]: 327.1855, found: 327.1856.

[0120] D33 yield 76%:1 H NMR (400 MHz, CDC13) δ 7.73 - 7.58 (m, 2H), 7.43 (s, 1H), 7.37 - 7.11 (m, 10H), 7.05 - 6.94 (m, 2H), 6.40 (m, 1H), 6.19 (m, 1H), 4.58 (m, 2H). 13 C NMR (101 MHz, CDC13) δ 159.1, 156.7, 144.2, 144.2, 136.6, 136.4, 132.6, 131.5, 128.7, 128.6, 128.0, 127.9, 126.5, 126.3, 121.7, 116.3, 116.2, 115.8, 115.6, 49.1. 19 F NMR (376 MHz, CDC13) δ = -123.94. HRMS (ESI) calcd. for C 22 H 20 FN2 [M+H]: 331.1605, found: 331.1603.

[0121] D34 yield 71%: 1 H NMR (400 MHz, CDC13) δ 7.73 - 7.61 (m, 2H), 7.49 (s, 1H), 7.41 - 7.11 (m, 10H), 7.09 - 6.99 (m, 1H), 6.67 - 6.55 (m, 1H), 6.39 (m, 1H), 6.18 (m, 1H), 4.59 (m, 2H). 13 C NMR (101 MHz, CDC13) δ 165.2, 162.8, 149.3, 149.2, 136.3, 133.6, 131.6, 130.4, 130.3, 128.7, 128.4, 127.9, 126.5, 121.3, 109.9, 107.3, 107.0, 102.3, 102.0, 48.3. 19 F NMR (376 MHz, CDC13) δ = -111.98. HRMS (ESI) calcd. for C 22 H 20 FN2 [M+H]: 331.1605, found: 331.1601.

[0122] D35 yield 61%: 1 H NMR (400 MHz, CDC13) δ 7.77 - 7.45 (m, 5H), 7.42 - 6.91 (m, 10H), 6.56 (m, 1H), 6.26 (m, 1H), 4.50 (m, 2H). 13C NMR (101 MHz, CDC13) δ 156.1, 153.6, 136.9, 136.5, 134.8, 132.2, 128.8, 128.2, 127.8, 126.6, 126.4, 125.1, 125.0, 124.8, 124.2, 116.9, 116.7, 54.7, 54.6. 19 F NMR (376 MHz, CDC13) δ = -122.05. HRMS (ESI) calcd for C 22 H 20 FN2 [M+H]: 331.1605, found: 331.1600.

[0123] D36 yield 75%: 1 H NMR (400 MHz, CDC13) δ 7.73 - 7.61 (m, 2H), 7.50 (s, 1H), 7.39 - 7.13 (m, 8H), 6.96 - 6.83 (m, 2H), 6.41 - 6.30 (m, 2H), 6.13 (m, 1H), 4.53 (m, 2H). 13 C NMR (101 MHz, CDC13) δ 165.3, 165.1, 162.9, 162.7, 149.8, 149.7, 149.6, 136.1, 135.9, 134.7, 131.8, 128.8, 128.7, 128.1, 126.7, 126.6, 120.8, 97.7, 97.6, 97.5, 97.4, 95.6, 95.4, 95.1, 48.0. 19 F NMR (376 MHz, CDC13) δ = -109.26. HRMS (ESI) calcd for C 22 H 19 F2N2 [M+H]: 349.1510, found: 349.1509.

[0124] D37 yield 81%: 1 H NMR (400 MHz, CDC13) δ 7.72 - 7.61 (m, 2H), 7.47 (s, 1H), 7.38 - 7.13 (m, 12H), 6.38 (dt, J = 16.1, 2.0 Hz, 1H), 6.18 (m, 1H), 4.59 (m, 2H). 13C NMR (101 MHz, CDC13) δ 148.7, 136.2, 135.1, 133.8, 131.6, 130.2, 128.7, 128.4, 128.0, 126.5, 121.2, 120.5, 114.9, 112.64, 48.2. HRMS (ESI) calcd. for C 22 H 20 Cl N2 [M+H]: 347.1309, found: 347.1306.

[0125] D38 yield 70%: 1 H NMR (400 MHz, CDC13) δ 7.76 - 7.60 (m, 2H), 7.53 - 7.42 (m, 2H), 7.40 - 7.13 (m, 10H), 6.94 - 6.83 (m, 1H), 6.38 (m, 1H), 6.18 (m, 1H), 4.59 (m, 2H). 13 C NMR (101 MHz, CDC13) δ 148.7, 136.2, 135.1, 133.8, 131.6, 130.2, 128.7, 128.4, 128.0, 126.5, 121.2, 120.5, 114.9, 112.64, 48.2. HRMS (ESI) calcd. for C 22 H 20 Cl N2 [M+H]: 347.1309, found: 347.1304.

[0126] D39 yield 60%: 1 H NMR (400 MHz, CDC13) δ 7.65 (m, 2H), 7.54 - 7.11 (m, 13H), 6.42 - 6.30 (m, 1H), 6.16 (m, 1H), 4.56 (m, 2H). 13 C NMR (101 MHz, CDC13) δ 148.7, 136.2, 135.1, 133.8, 131.6, 130.2, 128.7, 128.4, 128.0, 126.5, 121.2, 120.5, 114.9, 112.64, 48.2. HRMS (ESI) calcd. for C 22 H 20 Br N2 [M+H]: 391.0804, found: 391.0800.

[0127] D40 yield 48%: 1H NMR (400 MHz, CDC13) δ 7.73 - 7.64 (m, 2H), 7.61 (m, 1H), 7.51 (s, 1H), 7.40 - 7.11 (m, 10H), 7.05 (m, 1H), 6.40 (m, 1H), 6.22 (m, 1H), 4.64 (m, 2H). 13 C NMR (101 MHz, CDC13) δ 148.7, 136.2, 136.1, 133.8, 131.5, 130.4, 128.7, 128.4, 127.9, 126.5, 123.4, 123.3, 121.1, 117.7, 113.1, 48.3. HRMS (ESI) calcd. for C 22 H 20 Br N2[M+H]: 391.0804, found: 391.0801.

[0128] D41 yield 81%: 1 H NMR (400 MHz, CDC13) δ 7.70 (m, 2H), 7.62 - 7.52 (m, 3H), 7.46 (m, 2H), 7.43 - 7.13 (m, 8H), 6.41 (m, 1H), 6.25 (m, 1H), 4.72 (s, 2H). 13 C NMR (101 MHz, CDC13) δ 149.7, 136.1, 136.0, 134.5, 131.7, 128.7, 128.7, 128.6, 128.0, 126.5, 126.4, 120.8, 114.0, 47.9. 19 F NMR (376 MHz, CDC13) δ = -61.29. HRMS (ESI) calcd. for C 23 H 20 F3N2[M+H]: 381.1573, found: 381.1569.

[0129] D42 yield 83%: 1 H NMR (400 MHz, CDC13) δ 7.66 (d, J = 7.7 Hz, 2H), 7.48 (s,

[0130] 1H), 7.41 - 7.12 (m, 12H), 6.39 (d, J = 16.0 Hz, 1H), 6.19 (m, 1H), 4.67 - 4.54 (m, 2H). 13C NMR (101 MHz, CDC13) δ 146.3, 143.0, 136.3, 136.2, 133.4, 131.6, 128.7, 128.3, 128.0, 126.5, 126.4, 122.2, 122.1, 121.3, 115.4, 48.4. 19 F NMR (376 MHz, CDC13) δ = -58.05. HRMS (ESI) calcd for C 23 H 20 F3N2O [M+H]: 397.1522, found: 397.1518.

[0131] D43 yield 85%: 1 H NMR (400 MHz, CDC13) δ 8.07 (m, 1H), 7.81 (m, 1H), 7.69 (d, J = 8.0 Hz, 1H), 7.57 - 7.08 (m, 15H), 6.54 (d, J = 16.0 Hz, 1H), 6.40 (m, 1H), 4.57 (m, 2H). 13 C NMR (101 MHz, CDC13) δ 143.6, 137.1, 136.8, 135.1, 135.0, 132.5, 130.1, 128.8, 128.7, 127.8, 127.8, 127.1, 126.7, 126.6, 126.5, 126.2, 126.1, 125.7, 124.1, 123.7, 58.4. HRMS (ESI) calcd for C 26 H 23 N2 [M+H]: 363.1855, found: 363.1852.

[0132] D44 yield 58%: 1 H NMR (400 MHz, CDC13) δ 7.60 - 7.47 (m, 2H), 7.38 - 7.11 (m, 11H), 6.87 - 6.78 (m, 2H), 6.47 (m, 1H), 6.22 (m, 1H), 4.45 (s, 2H), 4.03 (m, 2H), 3.72 (s, 3H). 13 C NMR (101 MHz, CDC13) δ 156.0, 137.2, 137.0, 132.6, 132.1, 129.8, 129.1, 128.7, 128.6, 127.7, 127.4, 126.5, 125.7, 125.1, 114.1, 57.3, 55.5, 55.4. HRMS (ESI) calcd for C 24 H 25N2O [M+H]: 357.1961, found: 357.1961.

[0133] D45 yield 62%: 1 H NMR (400 MHz, CDCl3) δ 7.52 (d, J = 7.6 Hz, 2H), 7.29 (m,

[0134] 8H), 7.16 (m, 3H), 7.08 - 6.95 (m, 2H), 6.49 (d, J = 16.0 Hz, 1H), 6.23 (m, 1H), 4.56 (s, 2H), 4.10 (m, 2H). 13 C NMR (101 MHz, CDCl3) δ 162.0, 159.6, 137.1, 137.0, 132.8, 132.3, 130.2, 129.1, 129.0, 128.8, 128.7, 127.8, 127.5, 126.6, 125.8, 125.0, 124.8, 124.4, 124.4, 115.6, 115.4, 56.5, 51.0. 19 F NMR (376 MHz, CDCl3) δ = -117.81. HRMS (ESI) calcd. for C 23 H 22 FN2 [M+H]: 345.1761, found: 345.1762.

[0135] D46 yield 43%: 1 H NMR (400 MHz, CDCl3) δ 7.56 - 7.47 (m, 2H), 7.34 - 7.29 (m, 2H), 7.28 - 7.19 (m, 5H), 7.18 - 7.09 (m, 2H), 6.49 (d, J = 15.9 Hz, 1H), 6.28 - 6.12 (m, 1H), 3.93 (m, 2H), 1.34 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ 138.3, 137.3, 130.4, 129.4, 128.7, 128.6, 127.5, 126.8, 126.5, 126.2, 125.5, 60.0, 48.4, 28.5. HRMS (ESI) calcd. for C 24 H 25 N2O [M+H]:, found: 293.2013.

[0136] D47 yield 33%: 1H NMR (400 MHz, CDC13) δ 7.57 - 7.47 (m, 2 H), 7.39 - 7.10 (m, 9 H), 6.53 (m, 1 H), 6.23 (m, 1 H), 4.02 (m, 2 H), 3.31 (m, 1 H), 2.02 - 1.90 (m, 2 H), 1.83 (m, 2 H), 1.72 - 1.48 (m, 3 H), 1.42 - 1.06 (m, 3 H). 13 C NMR (101 MHz, CDC13) δ 137.8, 137.0, 130.8, 129.4, 128.6, 128.4, 127.4, 126.6, 126.3, 125.3, 125.2, 65.7, 50.6, 31.3, 26.0. HRMS (ESI) calcd. for C 24 H 25 N2O [M+H]:, found: 319.2170.

[0137] Preparation of allyl hydrazones D48-D61

[0138] Examples 103-116

[0139] Different from Example 1: A1 is replaced by A2, A3...A16. The specific data are shown as follows:

[0140]

[0141] Yield of D48 90%: 1 H NMR (400 MHz, CDC13) δ 7.72 - 7.61 (m, 2 H), 7.47 (s, 1 H), 7.44 - 7.38 (m, 2 H), 7.37 - 7.27 (m, 4 H), 7.26 - 7.17 (m, 3 H), 7.09 - 6.89 (m, 3 H), 6.40 (d, J = 16.1 Hz, 1 H), 6.20 - 6.11 (m, 1 H), 4.63 (m, 2 H), 2.27 (s, 3 H). 13 C NMR (101 MHz, CDC13) δ 147.7, 137.6, 136.8, 133.7, 132.5, 131.3, 129.4, 129.2, 128.7, 128.0, 126.4, 126.3, 120.7, 115.0, 48.6, 21.3. HRMS (ESI) calcd. for C 23 H 23 N2 [M+H]: 327.1855, found: 327.1855.

[0142] Yield of D49 87%: 1H NMR (400 MHz, CDC13) δ 7.66 (m, 2H), 7.48 - 7.35 (m, 3H), 7.35 - 7.24 (m, 4H), 7.20 (m, 1H), 7.09 (m, 3H), 6.93 (m, 2H), 6.36 (d, J = 15.7 Hz, 1H), 6.14 (m, 1H), 4.61 - 4.48 (m, 2H), 2.23 (m, 3H). 13 C NMR (101 MHz, CDC13) δ 147.8, 138.3, 136.9, 136.5, 132.6, 131.6, 129.4, 128.8, 128.7, 128.1, 127.5, 126.4, 123.6, 121.7, 120.9, 115.1, 48.5, 21.6. HRMS (ESI) calcd. for C 23 H 23 N2[M+H]: 327.1855, found: 327.1855.

[0143] D50 yield 85%: 1 H NMR (400 MHz, CDC13) δ 7.72 - 7.65 (m, 2H), 7.54 (s, 1H), 7.46 - 7.39 (m, 3H), 7.38 - 7.30 (m, 4H), 7.28 - 7.21 (m, 1H), 7.18 - 7.04 (m, 3H), 6.95 (m, 1H), 6.70 (m, 1H), 6.09 (m, 1H), 4.72 (m, 2H), 2.18 (s, 3H). 13 C NMR (101 MHz, CDC13) δ 147.7, 136.6, 135.8, 135.5, 132.6, 130.3, 129.9, 129.1, 128.6, 127.9, 127.6, 126.2, 126.1, 125.7, 123.2, 120.8, 115.1, 48.9, 19.8. HRMS (ESI) calcd. for C 23 H 23 N2[M+H]: 327.1855, found: 327.1855.

[0144] D51 yield 88%: 1H NMR (400 MHz, CDC13) δ 7.67 (m, 2H), 7.44 (s, 1H), 7.42-7.37 (m, 2H), 7.35-7.27 (m, 4H), 7.20 (m, 3H), 6.92 (m, 1H), 6.75 (d, J = 8.4 Hz, 2H), 6.33 (d, J = 16.0 Hz, 1H), 6.01 (m, 1H), 4.55 (m, 2H), 3.66 (s, 3H). 13 C NMR (101 MHz, CDC13) δ 159.4, 147.8, 136.8, 132.5, 130.8, 129.3, 128.7, 128.0, 127.7, 126.4, 120.8, 119.5, 115.0, 114.1, 55.4, 48.5. HRMS (ESI) calcd. for C 23 H 23 N2O [M+H]: 343.1805, found: 343.1802.

[0145] D52 yield 83%: 1 H NMR (400 MHz, CDC13) δ 7.71-7.65 (m, 2H), 7.55 (s, 1H), 7.45-7.40 (m, 2H), 7.38-7.28 (m, 5H), 7.26-7.12 (m, 2H), 6.98-6.75 (m, 4H), 6.29 (m, 1H), 4.68 (m, 2H), 3.73 (s, 3H). 13 C NMR (101 MHz, CDC13) δ 156.8, 147.8, 136.8, 132.5, 129.2, 128.8, 128.6, 127.8, 127.4, 127.2, 126.3, 123.1, 120.7, 115.1, 111.0, 55.4, 49.2. HRMS (ESI) calcd. for C 23 H 23 N2O [M+H]: 343.1805, found: 343.1801.

[0146] D53 yield 91%: 1 H NMR (400 MHz, CDC13) δ 7.73-7.61 (m, 2H), 7.46-7.13 (m, 10H), 6.97-6.80 (m, 3H), 6.38-6.27 (m, 1H), 6.07 (m, 1H), 4.56 (m, 2H). 13C NMR (101 MHz, CDC13) δ 163.7, 161.2, 147.7, 136.7, 132.7, 132.5, 130.2, 129.3, 128.8, 128.1, 128.0, 126.4, 121.6, 120.9, 115.7, 115.5, 115.0, 48.3. 19 F NMR (376 MHz, CDC13) δ = -113.90. HRMS (ESI) calcd for C 22 H 20 F N2 [M+H]: 331.1605, found: 331.1601.

[0147] D54 yield 91%: 1 H NMR (400 MHz, CDC13) δ 7.71 - 7.65 (m, 2H), 7.47 (s, 1H), 7.44 - 7.30 (m, 6H), 7.23 (m, 5H), 6.99 - 6.92 (m, 1H), 6.42 - 6.35 (m, 1H), 6.23 (m, 1H), 4.67 (m, 2H). 13 C NMR (101 MHz, CDC13) δ 147.5, 136.6, 134.9, 133.4, 132.5, 130.1, 129.2, 128.7, 128.6, 128.0, 127.6, 126.2, 122.5, 120.8, 114.9, 48.4. HRMS (ESI) calcd for C 22 H 20 Cl N2 [M+H]: 347.1309, found: 347.1308.

[0148] D55 yield 84%: 1 H NMR (400 MHz, CDC13) δ 7.73 - 7.65 (m, 2H), 7.46 (s, 1H), 7.43 - 7.21 (m, 9H), 7.21 - 7.13 (m, 2H), 6.99 - 6.91 (m, 1H), 6.41 - 6.32 (m, 1H), 6.29 - 6.19 (m, 1H), 4.67 (m, 2H). 13 C NMR (101 MHz, CDC13) δ 147.5, 136.5, 135.3, 132.5, 131.7, 130.2, 129.2, 128.6, 128.0, 126.2, 122.6, 121.5, 120.8, 114.9, 48.4. HRMS (ESI) calcd for C 22 H 20ClN2[M+H]: 347.1309, found: 347.1304.

[0149] D56 yield 86%: 1 H NMR (400 MHz, CDC13) δ 7.68 (m, 2H), 7.54 (s, 1H), 7.46 - 7.18 (m, 9H), 7.11 (m, 2H), 6.98 - 6.86 (m, 2H), 6.14 (m, 1H), 4.67 (m, 2H). 13 C NMR (101 MHz, CDC13) δ 147.6, 136.7, 134.9, 133.1, 132.7, 129.4, 129.2, 128.9, 128.8, 128.7, 128.0, 127.3, 127.0, 126.3, 125.6, 120.9, 115.2, 48.7. HRMS (ESI) calcd. for C 22 H 20 BrN2[M+H]: 391.0804, found: 391.0799.

[0150] D57 yield 90%: 1 H NMR (400 MHz, CDC13) δ 7.69 (m, 2H), 7.55 (s, 1H), 7.35 (m, 11H), 6.95 (m, 1H), 6.41 (dd, J = 16.2, 2.0 Hz, 1H), 6.28 (m, 1H), 4.63 (m, 2H). 13 C NMR (101 MHz, CDC13) δ 147.6, 137.2, 136.6, 132.5, 130.0, 129.8, 129.3, 129.1, 128.7, 128.1, 126.4, 124.4, 124.3, 124.2, 123.9, 123.1, 123.1, 123.0, 121.0, 114.9, 48.2. 19 F NMR (376 MHz, CDC13) δ = -62.53. HRMS (ESI) calcd. for C 23 H 20 F3N2[M+H]: 381.1573, found: 381.1568.

[0151] D58 yield 48%: 1H NMR (400 MHz, CDC13) δ 7.74 - 7.64 (m, 2H), 7.44 (s, 1H), 7.42 - 7.28 (m, 7H), 7.27 - 7.18 (m, 1H), 6.94 (m, 1H), 6.30 (m, 1H), 6.20 (m, 2H), 6.09 (m, 1H), 4.64 (m, 2H). 13 C NMR (101 MHz, CDC13) δ 152.2, 147.6, 142.0, 136.6, 132.5, 129.2, 128.6, 128.0, 126.3, 120.8, 120.3, 119.6, 114.8, 111.4, 108.3, 48.1. HRMS (ESI) calcd. for C 20 H 19 N2O [M+H]: 303.1491, found: 303.1486.

[0152] D59 yield 70%: 1 H NMR (400 MHz, CDC13) δ 7.59 (m, 2H), 7.37 (s, 1H), 7.32 - 7.18 (m, 6H), 7.18 - 7.12 (m, 1H), 6.83 (m, 1H), 5.52 - 5.27 (m, 2H), 4.37 (m, 2H), 1.97 - 1.85 (m, 2H), 1.25 (m, 2H), 0.75 (m, 3H). 13 C NMR (101 MHz, CDC13) δ 147.7, 136.9, 133.2, 132.2, 129.1, 128.6, 127.8, 126.1, 121.7, 120.5, 114.8, 48.1, 34.3, 22.3, 13.6. HRMS (ESI) calcd. for C 19 H 23 N2 [M+H]: 279.1855, found: 279.1855.

[0153] D60 yield 52%: 1 H NMR (400 MHz, CDC13) δ 7.67 (m, 2H), 7.43 (m, 1H), 7.39 - 7.16 (m, 7H), 6.91 (m, 1H), 5.73 (m, 1H), 5.59 - 5.27 (m, 2H), 4.98 - 4.85 (m, 2H), 4.45 (m, 2H), 2.02 (m, 4H), 1.58 - 1.33 (m, 2H). 13C NMR (101 MHz, CDC13) δ 147.6, 136.9, 132.0, 129.1, 128.6, 127.8, 127.7, 126.1, 126.1, 122.7, 120.4, 114.7, 47.8, 17.7. HRMS (ESI) calcd. for C 19 H 23 N2[M+H]: 279.1855, found: 279.1855.

[0154] D61 yield 76%: 1 H NMR (400 MHz, CDC13) δ 7.79 - 7.58 (m, 2H), 7.55 - 7.15 (m, 8H), 6.90 (m, 1H), 5.73 - 5.27 (m, 2H), 4.61 - 4.29 (m, 2H), 1.70 (m, 3H). 13 C NMR (101 MHz, CDC13) δ 147.6, 136.9, 132.0, 129.1, 128.6, 127.8, 127.7, 126.1, 126.1, 122.7, 120.4, 114.7, 47.8, 17.7. HRMS (ESI) calcd. for C 17 H 19 N2[M+H]: 251.1542, found: 251.1539.

[0155] The content described in the specification of the present application which is not described in detail belongs to the prior art known to the person skilled in the art. Although the above describes the specific embodiments of the present application in a demonstrative manner, so as to make the person skilled in the art understand the present application, it should be clear that the present application is not limited to the scope of the specific embodiments, and for the person skilled in the art, it is obvious that all kinds of changes are within the spirit and scope of the present application defined and determined by the appended claims, and all kinds of changes using the concept of the present application are included in the protection.

Claims

1. A method for one-step, efficient, green preparation of allyl thioacetate, characterized in that: The method comprises the following steps: The allyl hydrazone compound is obtained by cross-coupling reaction of enol, hydrazine and aldehyde under the action of a palladium catalyst, and a reaction route is as follows: ； wherein R 1 is selected from aliphatic substituent, substituted aryl or furanyl, R 2 is selected from aliphatic substituent, substituted aryl or naphthyl, R 3 is selected from aliphatic substituent, substituted aryl, naphthyl, furanyl or thienyl, R' is selected from hydrogen or aliphatic substituent; R 1 the fatty substituent is an alkyl group of 1 to 12 carbons, the substituted aryl group is a methyl aryl, methoxy aryl, phenyl aryl, fluoro aryl, chloro aryl, bromo aryl or trifluoromethyl aryl group; The R 2 The aliphatic substituents are tert-butyl, cyclohexyl, or substituted benzyl, and the substituted aryl groups are methylaryl, phenylaryl, fluoroaryl, chloroaryl, bromoaryl, trifluoromethylaryl, or trifluoromethoxyaryl. The R 3 The aliphatic substituents are benzyl or alkyl groups with 1-12 carbons, and the substituted aryl groups are methylaryl, tert-butylaryl, methoxyaryl, phenylaryl, biphenylaryl, fluoroaryl, chloroaryl, trifluoromethylaryl, trifluoromethoxyaryl, hydroxyaryl, nitroaryl, or N,N-dimethylaryl. The fatty substituent group in R' is an alkyl group with 1-12 carbons; When the palladium catalyst is one or more of PdCl2, PdBr2, PdI2, Pd(OAc)2, Pd(TFA)2, PdCl2(CH3CN)2, PdBr2(CH3CN)2, PdCl2(COD), PdBr2(COD), PdCl2(PhCN)2, [PdCl(CH2=CHCH2)]2 and [PdCl(PhCH2=CHCH2)]2, the preparation method of the allyl hydrazone further comprises adding a ligand, and the ligand is one of L1, L2, L3, L4, L5, L6 or L7, and the structural formula of each ligand is as follows: ； The coupling reaction temperature is 25-130 DEG C, and the time is 3-24 hours.

2. The process for one-step green preparation of allyl thioacetate according to claim 1, wherein: The amount of the catalyst is 0.1-10 % of the molar amount of the hydrazine.

3. The process for one step high efficient green preparation of allyl thioacetone according to claim 1, characterized in that: The solvent is any one of 1,4-dioxane, anisole, dimethyl ether, ethyl acetate, toluene, xylene, mesitylene, tetrahydrofuran, dichloromethane, dichloroethane or chloroform.

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