A method for one-step high-efficiency preparation of allyl acyl hydrazone

Abstract

The present application relates to a kind of one-step efficient preparation allyl acyl hydrazone method, specifically, using simple allyl alcohol, hydrazine and aldehyde as raw material, cross coupling reaction occurs under the action of CO and palladium catalyst, obtain allyl acyl hydrazone compound, belong to organic synthesis technical field.The reaction raw material used in the present application is cheap and easy to obtain, by coupling reaction, allyl acyl hydrazone compound can be efficiently prepared in one step;The reaction raw material and catalyst and ligand are cheap and easy to obtain, and the synthesis process is simple, which greatly reduces the synthesis cost;Reaction process is high in atomic economy, reaction product yield is excellent, and has excellent regioselectivity;Reaction conversion efficiency is higher, can realize gram-scale experiment, easy to realize industrialization.

Description

TECHNICAL FIELD

[0001] The present application relates to a kind of one-step efficient preparation allyl acyl hydrazone method, specifically, using simple allyl alcohol, hydrazine and aldehyde as raw material, cross coupling reaction occurs in CO and palladium catalyst, obtain allyl acyl hydrazone compound, belong to organic synthesis technical field. BACKGROUND

[0002] Allyl acyl hydrazone compound is an important class of compounds, because it contains allyl acyl hydrazone functional group in structure, widely exists in various natural products and medical and agricultural chemical, usually shows special value physical and chemical property and important biological activity.Allyl acyl hydrazone derivative can be used as attractive precursor, and can be easily converted into various important functional molecules.Therefore, the synthesis of the compound, especially developing a simple and environment-friendly synthesis path, is particularly important.

[0003] There are many synthesis methods of allyl acyl hydrazone compound, and the early preparation method is generally realized by multi-step reaction, and the reaction efficiency is low, the yield is low, and a large amount of by-products is generated, and the operation is complex.In order to solve the disadvantages brought by the reaction, transition metal catalyst is introduced in the reaction system, and allyl acyl hydrazone compound is prepared by one-step catalysis, which realizes good catalytic performance and substrate adaptability, but additional complex raw materials and active reagents are needed, which not only requires harsh reaction conditions, but also greatly reduces the reaction efficiency.

[0004] In order to solve such problems, a new synthesis method needs to be developed: without using external additive, only using metal catalyst to promote direct cross coupling of cheap and easily available allyl alcohol, hydrazine, aldehyde and CO to prepare allyl acyl hydrazone compound.At present, there is no related report on such reaction so far.

[0005] Therefore, it is an urgent problem to develop a kind of fast, practical and convenient synthesis method of allyl acyl hydrazone, which directly uses cross coupling reaction of allyl alcohol, hydrazine and aldehyde, under certain carbon monoxide pressure, to prepare allyl acyl hydrazone with wide substrate applicability with high atom economy, which has important theoretical significance and wide application prospect. SUMMARY

[0006] In view of the deficiencies of the prior art, the present application provides a one-step efficient preparation method of allyl acyl hydrazone.

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

[0008] A one-step efficient preparation method of allyl acyl hydrazone, comprising the following steps:

[0009] The allyl acylhydrazone compound is obtained by cross-coupling reaction of allyl alcohol, hydrazine and aldehyde in the presence of CO and palladium catalyst, and the reaction route is as follows:

[0010]

[0011] wherein R1 is selected from aliphatic substituent, substituted aryl or furanyl, R2 is selected from aliphatic substituent, substituted aryl or naphthyl, R3 is selected from aliphatic substituent, substituted aryl, naphthyl, furanyl or thienyl, and R' is selected from hydrogen or aliphatic substituent.

[0012] Further, the aliphatic substituent in R1 is alkyl of 1-12 carbons, and the substituted aryl is methyl aryl, methoxy aryl, phenyl aryl, fluoro aryl, chloro aryl, bromo aryl or trifluoromethyl aryl.

[0013] Further, the aliphatic substituent in R2 is t-butyl, cyclohexyl or substituted benzyl, and the substituted aryl is methyl aryl, phenyl aryl, fluoro aryl, chloro aryl, bromo aryl, trifluoromethyl aryl or trifluoromethoxy aryl.

[0014] Further, the aliphatic substituent in R3 is benzyl or alkyl of 1-12 carbons, and the substituted aryl is methyl aryl, t-butyl aryl, methoxy aryl, phenyl aryl, biphenyl aryl, fluoro aryl, chloro aryl, trifluoromethyl aryl, trifluoromethoxy aryl, hydroxy aryl, nitro aryl or N,N-dimethyl aryl.

[0015] Further, the aliphatic substituent in R' is alkyl of 1-12 carbons.

[0016] Further, when the palladium catalyst is one or more of PdCl2, Pd(OAc)2, Pd(TFA)2, PdCl2(CH3CN)2, PdBr2(CH3CN)2, PdCl2(COD), PdBr2(COD), [PdCl(CH2=CHCH2)]2, [PdCl(PhCH2=CHCH2)]2, PdCl2(Ph3P)2, PdCl2(Xantphos), [Pd(Cl)(C9H9)]2, the preparation method of the allyl acylhydrazone further comprises adding a ligand, and 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, Xan(o-tolyl)tphos, DPEphos, BIANP.

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

[0018] Further, the ligand includes monodentate ligand and bidentate ligand, the monodentate ligand is L1, i.e. ligand PPh2(3,5-Me2Ph), the amount of the monodentate ligand is 2 times of the amount of the catalyst; the bidentate ligand is L2, i.e. ligand NiXantphos, L3, i.e. ligand Sixantphos, L4, i.e. ligand Xant(o-tolyl)phos, L5, i.e. ligand Xantphos, L6, i.e. ligand DPEphos, L7, i.e. ligand BIANP, the amount of the bidentate ligand is the amount of the catalyst;

[0019] The structural formula of the L1-L7 is as follows:

[0020]

[0021] Further, the solvent is one of 1,4 dioxane, anisole, toluene, xylene, mesitylene, acetonitrile, dichloromethane, ethanol, preferably toluene.

[0022] Further, the CO reaction pressure is 1-5 MPa, the reaction temperature is 60-140 DEG C, and the reaction time is 2-15 hours.

[0023] Compared with the prior art, the present application has the following advantages:

[0024] 1. The reaction raw materials used in the present application are cheap and easy to obtain, and the allyl acylhydrazone compound can be efficiently prepared in one step through coupling reaction, the reaction raw materials, catalyst and ligand are cheap and easy to obtain, the synthesis process is simple, and the synthesis cost is greatly reduced.

[0025] 2. The present application can realize efficient synthesis of various substituted allyl acylhydrazone compounds, and the substrate applicability range is wide.

[0026] 3. The reaction process of the present application has high atom economy, the reaction product yield is excellent, and has excellent regioselectivity.

[0027] 4. The reaction conversion efficiency of the present application is high, and can realize gram-scale experiment, and is easy to realize industrialization. DETAILED DESCRIPTION

[0028] In order to facilitate the understanding of the present application, the present application will be described more fully below. However, the present application can be realized in many different forms, and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the disclosure of the present application more thorough and comprehensive.

[0029] Preparation of allyl acylhydrazone D1

[0030] The synthetic route is as follows:

[0031]

[0032] Example 1

[0033] In a glove box, a dry vial with magnetic stirring bar was charged with allyl alcohol Al (0.75 mmol), phenylhydrazine Bl (0.5 mmol), benzaldehyde Cl (0.7 mmol), PdCl2(Xantphos) 0.01 mmol, 2 mol%), and toluene (2.0 mL). The vial was sealed in an autoclave and taken out of the glove box. The autoclave was flushed with CO 3 times and charged with 4.0 MPa of CO. It was placed in a preheated metal bath at 120 °C for 12 h. The autoclave was allowed to cool down to room temperature and the vial was charged with n-hexadecane as internal standard. The yield of Dl was 85% by gas chromatography and 78% by column chromatography.

[0034] 1 H NMR (400 MHz, CDC13) δ 7.66 - 7.58 (m, 2H), δ 7.58 - 7.51 (m, 2H), δ 7.50 - 7.43 (m, 1H), δ 7.42 - 7.34 (m, 5H), 7.32 - 7.25 (m, 3H), 7.24 - 7.14 (m, 3H), 6.66 (d, J = 16.0 Hz, 1H), 6.60 - 6.49 (m, 1H), 4.05 - 3.89 (m, 2H). 13 C NMR (101 MHz, CDC13) δ = 173.0, 141.8, 137.3, 135.8, 134.3, 133.2, 130.3, 130.0, 129.4, 129.3, 128.8, 128.5, 127.3, 127.2, 126.3, 123.4, 38.7. MS (70 eV): m / z (%) = 340 [M] + (100), 210, 194, 117. HRMS (ESI) calcd for C 23 H 21 N2O [M+H]: 341.1609, found: 341.1610.

[0035] Examples 2-8

[0036] Different from Example 1: catalyst was replaced by PdCl2[CH3CN]2, and 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:

[0037]

[0038]

[0039] Examples 9-13

[0040] The difference from Example 6 is the kind of catalyst. Example 12 does not need to add ligand L5, i.e. Xantphos. The specific data are shown in the following table:

[0041]

[0042] Examples 14-17

[0043] The difference from Example 12 is the amount of PdCl2(Xantphos). The specific data are shown in the following table:

[0044]

[0045] Examples 18-21

[0046] The difference from Example 12 is the amount of toluene. The specific data are shown in the following table:

[0047]

[0048] Examples 22-27

[0049] The difference from Example 12 is the kind of solvent. The specific data are shown in the following table:

[0050]

[0051] Examples 28-30

[0052] The difference from Example 12 is the reaction pressure. The specific data are shown in the following table:

[0053]

[0054] Examples 31-34

[0055] The difference from Example 1 is the reaction temperature. The specific data are shown in the following table:

[0056]

[0057] Examples 35-40

[0058] The difference from Example 1 is the reaction time. The specific data are shown in the following table:

[0059]

[0060] Preparation of allyl acylhydrazones D2-D13

[0061] Examples 41-52

[0062] Instead of C1, C2, C3...C13 were used. The specific data are shown below:

[0063]

[0064]

[0065] Yield 78% of D2: 1 H NMR (400 MHz, CDC13) δ 7.59 - 7.43 (m, 5H), 7.42 - 7.37 (m, 2H), 7.32 - 7.26 (m, 2H), 7.25 - 7.14 (m, 6H), 6.66 (d, J = 16.0 Hz, 1H), 6.61 - 6.50 (m, 1H), 4.03 - 3.92 (m, 2H), 2.37 (s, 3H). 13 C NMR (101 MHz, CDC13) δ = 172.9, 141.9, 140.3, 137.4, 135.9, 133.1, 131.6, 130.2, 129.5, 129.3, 128.5, 127.3, 127.2, 126.3, 123.5, 38.7, 21.5. MS (70 eV): m / z (%) = 354 [M] + (100), 210, 194, 117. HRMS (ESI) calcd. for C 24 H 23 N2O [M+H]: 355.1805, found: 355.1804.

[0066] Yield 76% of D3: 1 H NMR (400 MHz, CDC13) δ 7.57 - 7.50 (m, 2H), 7.48 - 7.35 (m, 5H), 7.33 - 7.23 (m, 4H), 7.22 - 7.13 (m, 4H), 6.67 (d, J = 16.0 Hz, 1H), 6.60 - 6.50 (m, 1H), 4.06 - 3.88 (m, 2H), 2.35 (s, 3H). 13C NMR (101 MHz, CDC13) δ = 173.0, 142.1, 138.5, 137.4, 135.9, 134.3, 133.2, 130.9, 130.3, 129.4, 129.3, 128.7, 128.5, 127.9, 127.3, 126.3, 124.4, 123.4, 38.7, 21.4. MS (70 eV): m / z (%) = 354 [M] + (100), 210, 194, 117. HRMS (ESI) calcd. for C 24 H 23 N2O [M+H]: 355.1805, found: 355.1802.

[0067] D4 yield 76%: 1 H NMR (400 MHz, CDC13) δ 7.62 (s, 1H), 7.55 (t, J = 7.6 Hz, 2H), 7.49 - 7.43 (m, 1H), 7.41 - 7.35 (m, 2H), 7.32 - 7.26 (m, 2H), 7.26 - 7.16 (m, 3H), 6.86 (s, 2H), 6.63 - 6.48 (m, 2H), 3.97 - 3.82 (m, 2H), 2.29 (d, J = 13.6 Hz, 9H). 13 C NMR (101 MHz, CDC13) δ = 172.9, 142.8, 138.9, 137.5, 137.4, 136.1, 132.9, 130.3, 129.7, 129.3, 128.5, 128.1, 127.3, 126.3, 123.5, 38.4, 21.3, 21.1. MS (70 eV): m / z (%) = 382 [M] + (100), 224, 194, 117. HRMS (ESI) calcd. for C 26 H 27 N2O [M+H]: 383.2118, found: 383.2117.

[0068] D5 yield 73%: 1 H NMR (400 MHz, CDC13) δ 7.59 - 7.50 (m, 4H), 7.49 - 7.43 (m, 1H), 7.42 - 7.36 (m, 2H), 7.33 - 7.26 (m, 2H), 7.25 - 7.13 (m, 4H), 6.94 - 6.85 (m, 2H), 6.66 (d, J = 16.0 Hz, 1H), 6.61 - 6.50 (m, 1H), 4.04 - 3.90 (m, 2H), 3.81 (s, 3H).13 C NMR (101 MHz, CDC13) δ = 172.8, 161.1, 141.7, 137.4, 136.0, 133.1, 130.2, 129.3, 128.7, 128.5, 127.3, 127.1, 126.3, 123.5, 114.2, 55.4, 38.7. MS (70 eV): m / z (%) = 370 [M] + (100), 273, 194, 117. HRMS (ESI) calcd for C 24 H 23 N2O2[M+H]: 371.1754, found: 371.1757.

[0069] D6 yield 72%: 1 H NMR (400 MHz, CDC13) δ 7.59 - 7.51 (m, 2H), 7.50 - 7.42 (m, 1H), 7.42 - 7.36 (m, 2H), 7.31 - 7.25 (m, 3H), 7.23 (d, J = 1.2 Hz, 1H), 7.22 - 7.10 (m, 5H), 6.95 - 6.87 (m, 1H), 6.66 (d, J = 16.0 Hz, 1H), 6.61 - 6.49 (m, 1H), 4.03 - 3.92 (m, 2H), 3.80 (s, 3H). 13 C NMR (101 MHz, CDC13) δ = 172.9, 160.0, 141.7, 137.4, 135.9, 135.7, 133.2, 130.3, 129.8, 129.4, 129.3, 128.5, 127.4, 126.3, 123.4, 120.2, 116.0, 111.8, 55.4, 38.7. MS (70 eV): m / z (%) = 370 [M] + (100), 292, 194, 117. HRMS (ESI) calcd for C 24 H 23 N2O2[M+H]: 371.1754, found: 371.1759.

[0070] D7 yield 68%: 1H NMR (400 MHz, CDC13) δ 7.64 - 7.51 (m, 4H), 7.50 - 7.44 (m, 1H), 7.43 - 7.35 (m, 2H), 7.33 - 7.26 (m, 2H), 7.24 - 7.13 (m, 4H), 7.11 - 7.00 (m, 2H), 6.65 (d, J = 16.0 Hz, 1H), 6.59 - 6.48 (m, 1H), 4.09 - 3.83 (m, 2H). 13 C NMR (101 MHz, CDC13) δ = 172.9, 165.0, 162.5, 140.5, 137.3, 135.8, 133.2, 130.3, 129.4, 129.3, 129.1, 129.0, 128.5, 127.4, 126.3, 123.3. 116.0, 115.8, 38.7. 19 F NMR (376 MHz, CDC13) δ = -110.1. MS (70 eV): m / z (%) = 358 [M] + (100), 214, 195, 117. HRMS (ESI) calcd. for C 23 H 20 FN2O [M + H]: 359.1554, found: 359.1556.

[0071] D8 yield 59%: 1 H NMR (400 MHz, CDC13) δ 8.02 - 7.95 (m, 1H), 7.61 - 7.45 (m, 4H), 7.43 - 7.27 (m, 5H), 7.26 - 7.15 (m, 4H), 7.07 - 6.98 (m, 1H), 6.66 (d, J = 16.0 Hz, 1H), 6.61 - 6.5 (m, 1H), 4.08 - 3.82 (m, 2H). 13 C NMR (101 MHz, CDC13) δ = 173.0, 162.6, 160.1, 137.3, 133.2, 131.4, 131.3, 130.3, 129.5, 129.1, 128.5, 127.3, 126.6, 126.3, 124.5, 124.4, 123.2, 116.0, 115.8, 38.7. 19 F NMR (376 MHz, CDC13) δ = -120.7. MS (70 eV): m / z (%) = 358 [M] + (100), 214, 195, 117.

[0072] HRMS (ESI) calcd. for C 23 H20 FN2O[M+H]: 359.1554, found: 359.1557.

[0073] D9 yield 53%: 1 H NMR (400 MHz, CDC13) δ 8.11 - 8.01 (m, 1H), 7.71 (s, 1H), 7.56 (t, J = 7.6 Hz, 2H), 7.51 - 7.44 (m, 1H), 7.39 (d, J = 7.2 Hz, 2H), 7.35 - 7.25 (m, 5H), 7.24 - 7.15 (m, 3H), 6.65 (d, J = 16.0 Hz, 1H), 6.60 - 6.48 (m, 1H), 4.03 - 3.89 (m, 2H). 13 C NMR (101 MHz, CDC13) δ = 172.9, 138.7, 137.3, 135.7, 134.5, 133.3, 131.8, 130.8, 130.3, 129.9, 129.6, 129.0, 128.5, 127.4, 127.1, 127.0, 126.3, 123.2, 38.7. MS (70 eV): m / z (%) = 374 [M] + (100), 230, 195, 117. HRMS (ESI) calcd for C 23 H 20 ClN2O[M+H]: 375.1259, found: 375.1261.

[0074] D10 yield 52%: 1 H NMR (400 MHz, CDC13) δ 7.72 (d, J = 8.0 Hz, 2H), 7.63 (d,

[0075] J = 8.4 Hz, 2H), 7.60 - 7.54 (m, 2H), 7.53 - 7.45 (m, 1H), 7.39 (d, J = 7.6 Hz, 2H), 7.34 - 7.25 (m, 3H), 7.25 - 7.15 (m, 3H), 6.66 (d, J = 16.0 Hz, 1H), 6.59 - 6.46 (m, 1H), 4.11 - 3.80 (m, 2H). 13 C NMR (101 MHz, CDC13) δ = 173.0, 139.9, 137.7, 137.2, 135.6, 133.4, 130.4, 129.6, 129.1, 128.5, 127.4, 127.3, 126.3, 125.7, 123.0, 38.6. 19F NMR (376 MHz, CDC13) δ = -62.7. MS (70 eV): m / z (%) = 408 [M] + (100), 264, 117, 91. HRMS (ESI) calcd for C 24 H 20 F3N2O [M+H]: 409.1522, found: 409.1523.

[0076] D11 yield 63%: 1 H NMR (400 MHz, CDC13) δ 8.40 - 8.31 (m, 1H), 7.96 (s, 1H), 7.89 - 7.79 (m, 3H), 7.63 - 7.55 (m, 2H), 7.54 - 7.43 (m, 4H), 7.43 - 7.36 (m, 2H), 7.32 - 7.24 (m, 4H), 7.22 - 7.14 (m, 1H), 6.76 - 6.54 (m, 2H), 4.15 - 3.92 (m, 2H). 13 C NMR (101 MHz, CDC13) δ = 173.0, 141.6, 137.4, 135.9, 134.0, 133.3, 130.8, 130.6, 130.4, 129.8, 129.5, 129.4, 129.0, 128.6, 127.4, 127.1, 126.4, 126.2, 125.4, 123.7, 123.4, 38.8. MS (70 eV): m / z (%) = 390 [M] + (100), 245, 117, 91.

[0077] HRMS (ESI) calcd for C 27 H 23 N2O [M+H]: 391.1805, found: 391.1809.

[0078] D12 yield 33%: 1 H NMR (400 MHz, CDC13) δ 7.60 - 7.51 (m, 2H), 7.51 - 7.45 (m, 1H), 7.41 (d, J = 8.0 Hz, 3H), 7.36 (d, J = 5.2 Hz, 1H), 7.34 - 7.24 (m, 2H), 7.24 - 7.15 (m, 3H), 7.07 - 7.03 (m, 1H), 7.03 - 6.97 (m, 1H), 6.70 (d, J = 16.0 Hz, 1H), 6.62 - 6.47 (m, 1H), 4.01 - 3.75 (m, 2H). 13C NMR (101MHz, CDCl3) δ = 172.7, 139.7, 137.4, 136.2, 135.7, 133.3, 130.3, 129.7, 129. 5,129.2,128.5,127.8,127.5,127.3,126.3,123.3,38.8.MS(70eV):m / z(%)=346[M] + (100),202,186,117.HRMS(ESI)calcd.for C 21 H 19 N2OS[M+H]:347.1213,found:347.1217.

[0079] D13 yield 45% 1 H NMR(400MHz, CDCl3)δ8.24–8.15(m,1H),8.06(d,J=

[0080] 7.6Hz,1H),7.90–7.82(m,1H),7.62–7.52(m,2H),7.52–7.45(m,3H),7.44–7.37(m,4H),7.33 –7.14(m,6H),6.77–6.54(m,2H),4.34(q,J=7.2Hz,2H),4.12–3.95(m,2H),1.48–1.36(m,3H). 13 C NMR(101MHz, CDCl3)δ=172.8,143.3,141.0,140.4,137.5,133.1,130.2,129.5,129.2,128.5,127.3,126.3, 126.2,125.4,124.5,123.8,123.1,122.9,120.6,119.5,108.9,38.9,37.8,13.9.MS(70eV):m / z(%)=457[M] + (100),312,117,91.HRMS(ESI)calcd.for C 31 H 28 N3O[M+H]:458.2227,found:458.2225.

[0081] Preparation of allyl hydrazones D14-D19

[0082] Examples 53-58

[0083] The difference from Example 1 is that B1 is replaced by B2, B3...B7. Specific data is shown below:

[0084]

[0085] D14 yield 75%: 1 H NMR (400 MHz, CDC13) δ 7.67 - 7.54 (m, 2H), 7.43 - 7.25 (m, 10H), 7.24 - 7.16 (m, 1H), 7.09 - 7.00 (m, 2H), 6.66 (d, J = 16.0 Hz, 1H), 6.61 - 6.49 (m, 1H), 4.07 - 3.88 (m, 2H), 2.42 (s, 3H). 13 C NMR (101 MHz, CDC13) δ = 173.0, 141.7, 139.4, 137.4, 134.4, 133.1, 130.9, 129.9, 129.0, 128.8, 128.5, 127.3, 27.2, 126.3, 123.5, 38.8, 21.4. MS (70 eV): m / z (%) = 354 [M] + (100), 250, 210, 106. HRMS (ESI) calcd for C 24 H 23 N2O [M+H]: 355.1805, found: 355.1809.

[0086] D15 yield 70%: 1 H NMR (400 MHz, CDC13) δ 7.59 - 7.49 (m, 2H), 7.33 - 7.23 (m, 8H), 7.23 - 7.18 (m, 2H), 7.17 - 7.07 (m, 1H), 7.05 - 6.99 (m, 2H), 6.61 (d, J = 16.0 Hz, 1H), 6.55 - 6.42 (m, 1H), 3.98 - 3.83 (m, 2H), 2.00 (s, 3H). 13 C NMR (101 MHz, CDC13) δ = 172.6, 141.1, 137.4, 136.9, 134.6, 134.4, 133.3, 131.5, 130.0, 129.8, 129.3, 128.8, 128.5, 127.8, 127.3, 126.3, 123.3, 38.7, 17.4. MS (70 eV): m / z (%) = 354 [M] + (100), 250, 210, 117. HRMS (ESI) calcd for C 24 H 23 N2O [M+H]: 355.1805, found: 355.1805

[0087] D16 yield 61%:1 H NMR (400 MHz, CDC13) δ 7.66 - 7.57 (m, 2H), 7.56 - 7.50 (m, 2H), 7.44 - 7.36 (m, 5H), 7.34 - 7.25 (m, 3H), 7.24 - 7.18 (m, 1H), 7.17 - 7.10 (m, 2H), 6.66 (d, J = 16.0 Hz, 1H), 6.59 - 6.47 (m, 1H), 4.04 - 3.85 (m, 2H). 13 C NMR (101 MHz, CDC13) δ = 172.9, 142.0, 137.2, 135.4, 134.3, 134.0, 133.4, 130.7, 130.6, 130.2, 128.8, 128.5, 127.4, 127.2, 126.3, 123.0, 38.6. MS (70 eV): m / z (%) = 374 [M] + (100), 230, 180, 117. HRMS (ESI) calcd. for C 23 H 20 Cl N2O [M+H]: 375.1259, found: 375.1259.

[0088] D17 yield 53%: 1 H NMR (400 MHz, CDC13) δ 7.57 - 7.49 (m, 2H), 7.44 - 7.34 (m, 2H), 7.33 - 7.26 (m, 5H), 7.24 - 7.17 (m, 3H), 7.15 - 7.08 (m, 2H), 7.03 - 6.98 (m, 1H), 6.57 (d, J = 16.0 Hz, 1H), 6.51 - 6.38 (m, 1H), 4.02 - 3.71 (m, 2H). 13 C NMR (101 MHz, CDC13) δ = 171.8, 141.1, 136.2, 136.0, 134.7, 132.9, 132.4, 130.1, 129.1, 128.7, 128.6, 127.8, 127.5, 126.6, 126.3, 126.2, 125.2, 121.9, 37.5. MS (70 eV): m / z (%) = 374 [M] + (100), 230, 180, 117. HRMS (ESI) calcd. for C 23 H 20 Cl N2O [M+H]: 375.1259, found: 375.1259.

[0089] D18 yield 58%: 1H NMR (400 MHz, CDC13) δ 7.67 - 7.58 (m, 2H), 7.47 - 7.36 (m, 7H), 7.35 - 7.17 (m, 6H), 6.67 (d, J = 16.0 Hz, 1H), 6.59 - 6.47 (m, 1H), 4.06 - 3.80 (m, 2H). 13 C NMR (101 MHz, CDC13) δ = 173.0, 149.5, 142.0, 137.2, 134.1, 134.0, 133.4, 131.0, 130.2, 128.8, 128.5, 127.4, 127.3, 126.3, 122.9, 122.5, 121.7, 119.1, 38.6. 19 F NMR (376 MHz, CDC13) δ = -57.8. MS (70 eV): m / z (%) = 424 [M] + (100), 280, 239, 117. HRMS (ESI) calcd. for C 24 H 20 F3N2O2 [M + H]: 425.1471, found: 425.1469.

[0090] D19 yield 86%: 1 H NMR (400 MHz, CDC13) δ 7.66 (s, 1H), 7.63 - 7.56 (m, 2H), 7.42 - 7.31 (m, 5H), 7.31 - 7.23 (m, 2H), 7.22 - 7.14 (m, 1H), 7.14 - 7.09 (m, 2H), 6.84 - 6.79 (m, 2H), 6.63 (d, J = 16.0 Hz, 1H), 6.59 - 6.49 (m, 1H), 5.18 (s, 2H), 3.92 (d, J = 6.8 Hz, 2H), 3.71 (s, 3H). 13 C NMR (101 MHz, CDC13) δ = 173.4, 158.9, 140.1, 137.4, 134.7, 133.2, 129.8, 128.8, 128.6, 127.9, 127.4, 127.1, 127.0, 126.4, 123.6, 114.4, 55.3, 44.2, 38.5. MS (70 eV): m / z (%) = 384 [M] + (100), 280, 239, 117. HRMS (ESI) calcd. for C 25 H 25 N2O2 [M + H]: 385.1911, found: 385.1911.

[0091] Preparation of allyl acylhydrazones D20-D25

[0092] Examples 59-64

[0093] The difference from Example 1 is that A1 is replaced by A2, A3...A7. The specific data are shown below:

[0094]

[0095] Yield of D20 77%: 1 H NMR (400 MHz, CDC13) δ 7.65 - 7.58 (m, 2 H), 7.54 (t, J = 7.6 Hz, 2 H), 7.46 (t, J = 7.2 Hz, 1 H), 7.41 - 7.33 (m, 3 H), 7.32 - 7.23 (m, 3 H), 7.22 - 7.13 (m, 2 H), 7.10 (d, J = 8.0 Hz, 2 H), 6.63 (d, J = 16.0 Hz, 1 H), 6.56 - 6.44 (m, 1 H), 4.03 - 3.82 (m, 2 H), 2.31 (s, 3 H).

[0096] 7.6 Hz, 2 H), 7.46 (t, J = 7.2 Hz, 1 H), 7.41 - 7.33 (m, 3 H), 7.32 - 7.23 (m, 3 H), 7.22 - 7.13 (m, 2 H), 7.10 (d, J = 8.0 Hz, 2 H), 6.63 (d, J = 16.0 Hz, 1 H), 6.56 - 6.44 (m, 1 H), 4.03 - 3.82 (m, 2 H), 2.31 (s, 3 H). 13 C NMR (101 MHz, CDC13) δ = 173.1, 141.7, 137.1, 135.9, 134.6, 134.3, 133.1, 130.3, 130.0, 129.4, 129.3, 129.2, 128.8, 127.2, 126.2, 122.3, 38.7, 21.2. MS (70 eV): m / z (%) = 354 [M] + (100), 250, 196, 131. HRMS (ESI) calcd. for C 24 H 23 N2O [M + H]: 355.1805, found: 355.1807.

[0097] Yield of D21 66%: 1 H NMR (400 MHz, CDC13) δ 7.65 - 7.58 (m, 2 H), 7.57 - 7.51 (m, 2 H), 7.51 - 7.41 (m, 2 H), 7.40 - 7.30 (m, 3 H), 7.25 (s, 1 H), 7.23 - 7.14 (m, 3 H), 7.00 (d, J = 16.0 Hz, 1 H), 6.92 - 6.86 (m, 1 H), 6.85 - 6.81 (m, 1 H), 6.52 - 6.50 (m, 1 H), 4.05 - 3.94 (m, 2 H), 3.79 (s, 3 H). 13CNMR (101 MHz, CDC13) δ = 173.1, 156.6, 134.4, 130.2, 129.9, 129.3, 128.8, 128.4, 128.0, 127.3, 126.9, 126.5, 124.0, 120.7, 110.8, 55.5, 39.2. MS (70 eV): m / z (%) = 370 [M] + (100), 237, 196, 104. HRMS (ESI) calcd. for C 24 H 23 N2O2[M+H]: 371.1754, found: 371.1755.

[0098] D22 yield 63%: 1 H NMR (400 MHz, CDC13) δ 7.65 - 7.58 (m, 2H), 7.57 - 7.51 (m, 2H), 7.50 - 7.43 (m, 1H), 7.42 - 7.30 (m, 5H), 7.27 (s, 1H), 7.23 - 7.14 (m, 2H), 7.02 - 6.91 (m, 2H), 6.61 (d, J = 16.0 Hz, 1H), 6.52 - 6.38 (m, 1H), 4.08 - 3.82 (m, 2H). 13 C NMR (101 MHz, CDC13) δ = 172.9, 163.4, 161.0, 141.9, 135.8, 134.3, 133.6, 133.5, 132.0, 130.3, 130.0, 129.4, 129.3, 128.8, 127.8, 127.7, 127.2, 123.1, 115.5, 115.3, 38.6. 19 F NMR (376 MHz, CDC13) δ = -114.9. MS (70 eV): m / z (%) = 358 [M] + (100), 254, 196, 135. HRMS (ESI) calcd. for C 23 H 20 FN2O [M+H]: 359.1554, found: 359.1554.

[0099] D23 yield 53%: 1H NMR (400 MHz, CDCI3) δ 7.64 - 7.57 (m, 2H), 7.57 - 7.51 (m, 2H), 7.50 - 7.44 (m, 1H), 7.44 - 7.33 (m, 5H), 7.29 - 7.21 (m, 3H), 7.20 - 7.15 (m, 2H), 6.63 - 6.49 (m, 2H), 4.08 - 3.82 (m, 2H). 13 C NMR (101 MHz, CDCI3) δ = 172.7, 141.9, 136.3, 135.8, 134.2, 132.0, 131.6, 130.3, 130.0, 129.4, 129.2, 128.8, 127.9, 127.2, 124.3, 121.0, 38.6. MS (70 eV): m / z (%) = 418 [M] + (100), 293, 196, 104. HRMS (ESI) calcd. for C 23 H 20 BrN2O [M+H]: 419.0754, found: 419.0750.

[0100] D 24 Yield 58%: 1 H NMR (400 MHz, CDCI3) δ 7.67 - 7.53 (m, 6H), 7.52 - 7.44 (m, 2H), 7.43 - 7.35 (m, 4H), 7.29 (s, 1H), 7.23 - 7.16 (m, 2H), 6.75 - 6.57 (m, 2H), 4.16 - 3.84 (m, 2H). 13 C NMR (101 MHz, CDCI3) δ = 172.6, 142.1, 138.1, 134.2, 131.8, 130.3, 130.1, 129.4, 129.2, 128.9, 128.8, 127.2, 125.6, 123.9, 123.8, 123.1, 123.0, 38.4. 19 F NMR (376 MHz, CDCI3) δ = -62.7. MS (70 eV): m / z (%) = 408 [M] + (100), 248, 196, 165. HRMS (ESI) calcd. for C 24 H 20 F3N2O [M+H]: 409.1522, found: 409.1522.

[0101] D 25 Yield 36%: 1H NMR (400 MHz, CDC13) δ 7.64 - 7.51 (m, 4H), 7.50 - 7.44 (m, 1H), 7.41 - 7.31 (m, 3H), 7.24 (d, J = 8.0 Hz, 1H), 7.20 - 7.12 (m, 2H), 5.85 - 5.55 (m, 2H), 3.90 - 3.66 (m, 2H), 2.25 - 1.98 (m, 2H), 1.52 - 1.33 (m, 2H), 1.02 - 0.84 (m, 3H). 13 C NMR (101 MHz, CDC13) δ = 173.7, 141.4, 136.0, 134.4, 132.9, 130.2, 129.8, 129.3, 128.7, 127.2, 123.0, 122.3, 38.4, 34.8, 22.7, 22.5, 13.9, 13.7. MS (70 eV): m / z (%) = 306 [M] + (100), 277, 196, 104. HRMS (ESI) calcd. for C 20 H 23 N2O [M+H]: 307.1805, found: 307.1805.

[0102] 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, as long as various changes are within the spirit and scope of the present application defined and determined by the appended claims, all the inventions utilizing the concept of the present application are included in the protection.

Claims

1. A process for the one-step high efficient preparation of allyl acyl hydrazone, characterized in that, The method comprises the following steps: The allyl acylhydrazone compound is obtained by cross-coupling reaction of allyl alcohol, hydrazine and aldehyde under the action of CO and a palladium catalyst, and a reaction route thereof is as follows: ； R1 is selected from a fatty substituent group, a substituted aryl group or a furanyl 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 furanyl group or a thiophenyl group, and R' is selected from hydrogen or a fatty substituent group; 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; 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; 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; The fatty substituent group in R' is an alkyl group with 1-12 carbons; When the palladium catalyst is one or more of PdCl2, Pd(OAc)2, Pd(TFA)2, PdCl2(CH3CN)2, PdBr2(CH3CN)2, PdCl2(COD), PdBr2(COD), [PdCl(CH2=CHCH2)]2, [PdCl(PhCH2=CHCH2)]2, PdCl2(Ph3P)2, PdCl2(Xantphos), [Pd(Cl)(C9H9)]2, the preparation method of the allyl acylhydrazone further comprises adding a ligand, and the ligand is NiXantphos, Sixantphos, Xant(o-tolyl)phos and Xantphos, and the structural formulae of the ligands are as follows: ； The amount of the palladium catalyst is 0.1-10 % of the molar amount of the hydrazine; The solvent is one of 1,4-dioxane, anisole, toluene, xylene, mesitylene, dichloromethane and ethanol; The CO reaction pressure is 1-5 MPa, the reaction temperature is 60-140 DEG C, and the reaction time is 2-15 hours.

Images