Synthesis method of trans-N-alkenyl pyridine-2 (1H)-ketone compound

Abstract

The invention relates to the field of organic chemical industry, and particularly discloses a synthesis method of a trans-N-alkenyl pyridine-2 (1H)-ketone compound. A pyridone compound and a terminal alkyne compound are used as raw materials and react in an organic solvent in the presence of a ruthenium catalyst and a phosphorus ligand to obtain the trans-N-alkenyl pyridine-2 (1H)-ketone compound. The green synthesis method of the trans-N-alkenyl pyridine-2 (1H)-ketone series compounds is realized through C-H bond activation under mild conditions, and the method has the advantages of wide raw material source, simplicity and convenience in operation, easiness in separation and purification, higher yield and the like.

Description

Technical Field

[0001] The present invention relates to the fields of medicine, organic chemical industry and fine chemical industry, and in particular to a method for synthesizing EN-alkenyl-pyridin-2(1H)-one (trans-N-alkenylpyridin-2(1H)-one) compounds simply and efficiently by using pyridone compounds and terminal alkyne compounds as raw materials, in the presence of a ruthenium catalyst and a phosphorus ligand, and using 1,4-dioxane as a solvent. Background Art

[0002] 2-Pyridone fragments are present in many biologically relevant compounds, including some drugs that have been approved by the FDA for the treatment of cancer, HIV or pulmonary fibrosis. Currently, these compounds are mainly synthesized by metal-catalyzed CH activation methods. As shown below, there are several synthesis methods:

[0003]

[0004] The methods for preparing trans-N-alkenylpyridin-2(1H)-one compounds often use halides as starting materials, resulting in numerous reaction steps and complex conditions. Alternatively, vinylboronic acid and pyridone are coupled under an equivalent amount of copper catalysis to generate products, or potassium trifluoroborate and pyridone are cross-coupled under copper catalysis to effectively synthesize products, or vinylbenzene and pyridone are synthesized under three equivalents of silver catalyst. These methods require equivalent catalysts, so it is of great research value to develop a green synthesis method for trans-N-alkenylpyridin-2(1H)-one series compounds by CH bond activation under mild conditions. Summary of the invention

[0005] In view of the shortcomings of the prior art, the present invention uses cheap and readily available pyridone compounds and terminal alkyne compounds as starting materials, and synthesizes a series of trans-N-alkenylpyridin-2(1H)-one compounds under the action of a transition metal ruthenium catalyst. The method of the present invention has the advantages of a wide source of raw materials, simple operation, easy separation and purification, and high yield.

[0006] The synthesis method of the trans-N-alkenylpyridine-2(1H)-one compounds of the present invention is as follows: under a nitrogen atmosphere, under the action of a ruthenium catalyst, using the pyridone compound shown in formula 1 and the terminal alkyne compound shown in formula 2 as raw materials, with the participation of a phosphorus ligand, a reaction is carried out in an organic solvent to synthesize the target compound.

[0007] The specific process of the reaction is as follows:

[0008]

[0009] Wherein R1 is one of hydrogen, alkyl, fluorine, chlorine, bromine, methoxy, and ester groups; and R2 is one of aryl, substituted aryl or alkyl (C1-C10), and substituted alkyl (C1-C10).

[0010] Furthermore, the ruthenium catalyst is one of bis-(2-methylallyl)cyclooctane-1,5-diene ruthenium (Ru(methallyl)2COD), ruthenium trichloride, bis(tricyclohexylphosphine)benzylidene ruthenium dichloride), ruthenium iodide, and ruthenium acetate. Preferably, the ruthenium catalyst is bis-(2-methylallyl)cyclooctane-1,5-diene ruthenium (Ru(methallyl)2COD).

[0011] Furthermore, the organic solvent is one of toluene, xylene, nitrobenzene, chlorobenzene, fluorobenzene, 1,4-dioxane, trifluorotoluene, and mesitylene. Preferably, the organic solvent is 1,4-dioxane.

[0012] Further, the ligand is: 5-[6-(dibenzo[d,f][1,3,2]dioxaphosphoryl)]-5H-dibenzo[b,f]azepine, the structural formula is Bipyridine, (2S,4S)-(-)-2,4-bis(diphenylphosphino)pentane, Xantphos, triisopropylphosphine, triisopropylphosphine, 1,1'-binaphthyl-2,2'-bisdiphenylphosphine (Binap), 1,4-bis(diphenylphosphino)butane (dppb), (6,6'-dimethoxy-[1,1'-biphenyl]-2,2'-diyl)bis(diphenylphosphine), dppf, dppa, 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (Xphos), 2-dicyclohexylphosphino-2',6'-dimethoxy-biphenyl (Sphos), N, N-dimethyl dinaphtho[2,1-d:1',2'-f][1,3,2]dioxophosphine-4-amine, the structural formula is One of tricyclohexylphosphine, bis(dicyclohexylphosphine)methane, 1,2-bis(dicyclohexylphosphine)-ethane, 1,3-bis(dicyclohexylphosphine)propane, 1,4-bis(dicyclohexylphosphine)butane

[0013] Furthermore, the reaction temperature is 80-120° C., and the reaction time is 15-26 h.

[0014] Furthermore, the equivalent ratio of the ruthenium catalyst, the phosphorus ligand, the pyridone compound and the terminal alkyne compound is (0.05-0.10):(0.06-0.12):(1):(1-2). Preferably, the equivalent ratio of the ruthenium catalyst, the phosphorus ligand, the pyridone compound and the terminal alkyne compound is 0.05:0.06:1:2.

[0015] Furthermore, the reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography (petroleum ether / ethyl acetate=4:1) to obtain the target compound.

[0016] Compared with the prior art, the present invention has the following beneficial effects:

[0017] The post-reaction treatment of the present invention is simple and convenient, and only a simple column chromatography separation method is required, and a mixed solvent of petroleum ether and ethyl acetate is used as an eluent to obtain a pure trans-N-alkenylpyridine-2(1H)-one compound. The raw materials pyridone and terminal alkyne used in the present invention are obtained by commercial purchase. The present invention provides a more concise and feasible way for the synthesis of trans-N-alkenylpyridine-2(1H)-one compounds, and has important application value. DETAILED DESCRIPTION

[0018] The present invention is described in detail below in conjunction with embodiments, and each embodiment of the present invention is as follows:

[0019] Example 1

[0020] (E)-1-(4-Chlorostyryl)pyridin-2(1H)-one

[0021]

[0022] Under nitrogen atmosphere, the catalyst (Ru(methallyl)2COD) (47.9 mg, 0.15 mmol, 5.0 mol%) and tributylphosphine ligand (0.18 mmol, 6.0 mol%) were dissolved in 6 mL of toluene and stirred for 5 minutes. Then it was added to a 10 mL reaction bottle of pyridone (3 mmol, 1.0 eq.) and p-chlorophenylacetylene (3 mmol, 1.0 eq.) where R is p-chlorophenyl. The reaction mixture was stirred at 90°C for 26 hours. The reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 4:1) to obtain the target compound with a calculated yield of 47%.

[0023] NMR data: 1 H NMR (400MHz, CDCl3) δ7.98 (d, J = 14.9HZ, 1H), 7.61 (dd, J1 = 7.1HZ, J2 = 1.4Hz, 1H), 7.41-7.26 (m, 5H), 6.66-6.61 (m, 2H), 6.27 (t, J = 6.8HZ, 1H) ppm.

[0024] 13C NMR (100MHz, CDCl3) δ161.4,139.5,133.9,133.2,132.5,129.0,127.8,126.3,121.6,119.8,106.9ppm.

[0025] Example 1 (1)

[0026] On the basis of Example 1, the influence of the type of ruthenium catalyst was studied. Except for the ruthenium catalyst, other conditions were the same as those in Example 1.

[0027] Table 1

[0028] Ruthenium catalyst Yield Ruthenium trichloride 13％ (1,5-Cyclooctadiene)ruthenium chloride polymer <5％ Bis(tricyclohexylphosphine)benzylideneruthenium dichloride 16％ Ruthenium iodide 23％ Ruthenium acetate 12％ Triphenylphosphine ruthenium chloride <5％ Dichloro(pentamethylcyclopentadienyl)ruthenium(III) polymer <5％ Tris(2,2-bipyridyl)ruthenium chloride hexahydrate <5％

[0029] Example 1 (2)

[0030] On the basis of Example 1, the influence of the solvent type was studied. Except for the solvent, other conditions were the same as those in Example 1.

[0031] Table 2

[0032] Solvents Yield Toluene 47％ Xylene 38％ Nitrobenzene 24％ Tetrahydrofuran <5％ 1,2-Dichloroethane <5％ Chloroform <5％ Tetrachloromethane <5％ chlorobenzene 40％ Fluorobenzene 35％ Dichloromethane <5％ 1,4-Dioxane 53％ Trifluorotoluene 15％ Mesitylene 36％ n-Hexane 5％

[0033] From the above screening, 1,4-dioxane was selected as the optimal solvent.

[0034] Example 1 (3)

[0035] The reaction catalyst is bis-(2-methylallyl)cyclooct-1,5-dieneruthenium, the stoichiometric ratio of pyridone to terminal alkyne is 1:1, the temperature is 90 degrees Celsius, the reaction solvent is 1,4-dioxane, and the other reaction conditions are the same as those in Example 1.

[0036] Under nitrogen atmosphere, the catalyst (Ru(methallyl)2COD) (47.9 mg, 0.15 mmol, 5.0 mol%) and the ligand (6.0 mol%) were dissolved in 6 mL 1,4-dioxane and stirred for 5 minutes. Then it was added to a 10 mL reaction bottle of pyridone (3 mmol, 1.0 eq) and p-chlorophenylacetylene (3 mmol, 1.0 eq). The reaction mixture was stirred at 90 ° C for 26 hours. The reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 4:1) to obtain the target compound.

[0037] Study the effect of ligand type.

[0038] Table 3

[0039]

[0040]

[0041] The optimal ligand is 5-[6-(dibenzo[d,f][1,3,2]dioxaphosphoryl)]-5H-dibenzo[b,f]azepine. The structure is as follows:

[0042]

[0043] Example 1 (4)

[0044] (E)-1-(4-Chlorostyryl)pyridin-2(1H)-one

[0045]

[0046] Under nitrogen atmosphere, catalyst Ru(methallyl)2COD (47.9 mg, 0.15 mmol, 5.0 mol%) and ligand 5-[6-(dibenzo[d,f][1,3,2]dioxaphosphoryl)]-5H-dibenzo[b,f]azepine (73.7 mg, 0.18 mmol, 6.0 mol%) were dissolved in 6 mL 1,4-dioxane and stirred for 5 minutes. Then, it was added to a 10 mL reaction bottle containing pyridone (3 mmol, 1.0 eq.) with R as H and p-chlorophenylacetylene (6 mmol, 2.0 eq.) with R as p-chlorophenyl. The reaction mixture was stirred at 90°C for 26 hours. The reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 4:1) to obtain the target compound as a yellow solid (453 mg) with a calculated yield of 65%.

[0047] Example 1 (5)

[0048] Compared with Example 1 (4), the difference is that the equivalent ratio of ruthenium catalyst, ligand, pyridone and chlorophenylacetylene is different, and the other operations are the same as Example 1 (4).

[0049] When the equivalent ratio of ruthenium catalyst, ligand, pyridone and chlorophenylacetylene is 0.05:0.06:1:1, the yield is 58%;

[0050] When the equivalent ratio of ruthenium catalyst, phosphoramidite ligand, pyridone and terminal alkyne is 0.05:0.06:1:1.5, the yield is 60%.

[0051] Example 1 (6)

[0052] Based on the basic technology of Example 1(4), the effect of reaction temperature was studied.

[0053] Table 4

[0054]

[0055]

[0056] Example 2

[0057] (E)-1-(Dec-1-en-1-yl)-4-methylpyridin-2(1H)-one

[0058]

[0059] Under nitrogen atmosphere, a ruthenium catalyst such as Ru(methallyl)2COD (47.9 mg, 0.15 mmol, 5.0 mol%) and a ligand 5-[6-(dibenzo[d,f][1,3,2]dioxaphosphoryl)]-5H-dibenzo[b,f]azepine (73.7 mg, 0.18 mmol, 6.0 mol%) were dissolved in 6 mL 1,4-dioxane and stirred for 10 minutes. Then, it was added to a 10 mL reaction bottle containing pyridone (3 mmol, 1.0 eq.) and quinine (6 mmol, 2.0 eq.) with R being Me. The reaction mixture was stirred at 90°C for 24 hours. The reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 4:1) to obtain the target compound as a transparent liquid of 467 mg with a calculated yield of 63%.

[0060] NMR data: 1 H NMR (400MHz, CDCl3) δ7.27(d,J=6.68Hz,1H),7.20(d,J=14.32Hz,1H),7.10(d,J=6.64Hz,1H),6.04(t,J=6.84H z,1H),5.73-5.63(m,1H),2.13(q,J=7.36Hz,2H),2.07(s,3H),1.44-1.11(m,12H),0.81(t,J=6.96Hz,3H),ppm.

[0061] 13 C NMR (100MHz, CDCl3) δ161.8,136.4,131.1,130.1,126.9,122.9,105.9,31.8,30.0,29.34,29.27,29.2,29.1,22.6,17.2,14.0ppm.

[0062] Embodiment 3:

[0063] (E)-4-Chloro-1-(dec-1-en-1-yl)pyridin-2(1H)-one

[0064]

[0065] Under nitrogen atmosphere, a ruthenium catalyst such as Ru(methallyl)2COD (47.9 mg, 0.15 mmol, 5.0 mol%) and a ligand 5-[6-(dibenzo[d,f][1,3,2]dioxaphosphoryl)]-5H-dibenzo[b,f]azepine (73.7 mg, 0.18 mmol, 6.0 mol%) were dissolved in 6 mL 1,4-dioxane and stirred for 10 minutes. Then, it was added to a 10 mL reaction bottle containing pyridone (3 mmol, 1.0 eq.) and quinine (6 mmol, 2.0 eq.) with R as Cl. The reaction mixture was stirred at 90°C for 15 hours. The reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 4:1) to obtain the target compound as a transparent liquid 544 mg with a calculated yield of 68%.

[0066] NMR data: 1 H NMR (400MHz, CDCl3) δ7.39(d,J=7.48Hz,1H),7.11(d,J=14.28Hz,1H),6.57(d,J=2.12Hz,1H),6.19(dd,J =7.44Hz,1H),5.81-5.70(m,1H),2.17(q,J=6.96Hz,2H),1.50-1.14(m,12H),0.85(t,J=6.96Hz,3H)ppm.

[0067] 13 C NMR (100MHz, CDCl3) δ160.2,146.6,133.9,125.9,124.1,119.4,108.1,31.7,30.0,29.3,29.15,29.08,29.0,22.6,14.0ppm.

[0068] Embodiment 4:

[0069] (E)-4-Chloro-1-(dec-1-en-1-yl)pyridin-2(1H)-one 5m

[0070]

[0071] Under nitrogen atmosphere, a ruthenium catalyst such as Ru(methallyl)2COD (47.9 mg, 0.15 mmol, 5.0 mol%) and a ligand 5-[6-(dibenzo[d,f][1,3,2]dioxaphosphoryl)]-5H-dibenzo[b,f]azepine (73.7 mg, 0.18 mmol, 6.0 mol%) were dissolved in 6 mL 1,4-dioxane and stirred for 10 minutes. Then, it was added to a 10 mL reaction bottle containing pyridone (3 mmol, 1.0 eq.) and quinine (6 mmol, 2.0 eq.) with R being bromine. The reaction mixture was stirred at 90°C for 26 hours. The reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 4:1) to obtain the target compound as a transparent liquid of 481 mg with a calculated yield of 62%.

[0072] NMR data: 1 H NMR (400MHz, CDCl3) δ7.31 (d, J = 7.44Hz, 1H), 7.11 (d, J = 14.28Hz, 1H), 6.79 (d, J = 2.08Hz, 1H), 6.33 (dd, J = 7.40Hz, 1H),5.82-5.72(m,1H),2.17(q,J=7.32Hz,2H),1.50-1.37(m,2H),1.35-1.18(m,10H),0.86(t,J=7.04Hz,3H),ppm.

[0073] 13 C NMR (100MHz, CDCl3) δ160.0,135.5,133.6,126.0,124.2,123.1,110.6,31.8,30.0,29.3,29.26,29.15,29.08,22.6,14.0ppm.

[0074] Embodiment 5:

[0075] (E)-1-(Dec-1-en-1-yl)-5-methylpyridin-2(1H)-one

[0076]

[0077] Under nitrogen atmosphere, a ruthenium catalyst such as Ru(methallyl)2COD (47.9 mg, 0.15 mmol, 5.0 mol%) and a ligand 5-[6-(dibenzo[d,f][1,3,2]dioxaphosphoryl)]-5H-dibenzo[b,f]azepine (73.7 mg, 0.18 mmol, 6.0 mol%) were dissolved in 6 mL 1,4-dioxane and stirred for 10 minutes. Then, it was added to a 10 mL reaction bottle containing pyridone (3 mmol, 1.0 eq.) and quinine (6 mmol, 2.0 eq.) with R being Me. The reaction mixture was stirred at 90°C for 25 hours. The reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 4:1) to obtain the target compound as a transparent liquid of 475 mg with a calculated yield of 65%.

[0078] NMR data: 1 H NMR (400MHz, CDCl3) δ7.23-7.15(m,2H),7.13(dd,J=9.28Hz,1H),6.46(d,J=9.24Hz,1H),5.77-5 .66(m,1H),2.15(q,J=7.56Hz,2H),2.05(s,3H),1.48-1.14(m,12H),0.84(t,J=7.04Hz,3H),ppm.

[0079] 13 C NMR (100MHz, CDCl3) δ160.6,142.0,130.8,126.5,122.6,120.7,115.2,31.8,30.0,29.3,29.2,29.1,29.0,22.6,17.1,14.0ppm.

[0080] Embodiment 6:

[0081] (E)-5-Chloro-1-(dec-1-en-1-yl)pyridin-2(1H)-one

[0082]

[0083] Under nitrogen atmosphere, a ruthenium catalyst such as Ru(methallyl)2COD (47.9 mg, 0.15 mmol, 5.0 mol%) and a ligand 5-[6-(dibenzo[d,f][1,3,2]dioxaphosphoryl)]-5H-dibenzo[b,f]azepine (73.7 mg, 0.18 mmol, 6.0 mol%) were dissolved in 6 mL 1,4-dioxane and stirred for 10 minutes. Then it was added to a 10 mL reaction bottle containing pyridone (3 mmol, 1.0 eq) and quinine (6 mmol, 2.0 eq) with R as Cl. The reaction mixture was stirred at 90°C for 26 hours. The reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 4:1) to obtain the target compound as a transparent liquid 475 mg with a calculated yield of 60%

[0084] NMR data: 1 H NMR (400MHz, CDCl3) δ7.48(d,J=2.64Hz,1H),7.23(dd,J=9.72Hz,1H),7.14(d,J=14.24Hz,1H),6.50(d,J =9.72Hz,1H),5.82-5.71(m,1H),2.17(q,J=7.08Hz,2H),1.49-1.15(m,12H),0.85(t,J=7.00Hz,3H),ppm.

[0085] 13 C NMR (100MHz, CDCl3) δ159.6,140.2,131.1,125.8,123.9,122.0,113.0,31.7,30.0,29.3,29.12,29.07,29.0,22.6,14.1ppm.

[0086] Embodiment 7:

[0087] (E)-1-(Dec-1-en-1-yl)pyridin-2(1H)-one

[0088]

[0089] Under nitrogen atmosphere, a ruthenium catalyst such as Ru(methallyl)2COD (47.9 mg, 0.15 mmol, 5.0 mol%) and a ligand 5-[6-(dibenzo[d,f][1,3,2]dioxaphosphoryl)]-5H-dibenzo[b,f]azepine (73.7 mg, 0.18 mmol, 6.0 mol%) were dissolved in 6 mL 1,4-dioxane and stirred for 10 minutes. Then, it was added to a 10 mL reaction bottle containing pyridone (3 mmol, 1.0 eq.) and quinine (6 mmol, 2.0 eq.) with R being H. The reaction mixture was stirred at 90°C for 26 hours. The reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 4:1) to obtain the target compound as a transparent liquid of 363 mg with a calculated yield of 78%.

[0090] NMR data: 1 H NMR (400MHz, CDCl3) δ7.45(d,J=6.84Hz,1H),7.34-7.27(m,1H),7.22(d,J=14.32Hz,1H),6.54(d,J=9.20Hz,1H),6 .17(t,J=6.72Hz,1H),5.80-5.70(m,1H),2.19(q,J=7.28Hz,2H),1.52-1.15(m,12H),0.87(t,J=6.88Hz,3H),ppm.

[0091] 13 C NMR (100MHz, CDCl3) δ161.5,139.4,133.8,126.8,123.6,121.3,106.3,31.9,30.1,29.4,29.3,29.2,29.1,22.7,14.1ppm.

[0092] Embodiment 8:

[0093] (E)-1-(Oct-1-en-1-yl)pyridin-2(1H)-one

[0094]

[0095] Under nitrogen atmosphere, a ruthenium catalyst such as Ru(methallyl)2COD (47.9 mg, 0.15 mmol, 5.0 mol%) and a ligand 5-[6-(dibenzo[d,f][1,3,2]dioxaphosphoryl)]-5H-dibenzo[b,f]azepine (73.7 mg, 0.18 mmol, 6.0 mol%) were dissolved in 6 mL 1,4-dioxane and stirred for 10 minutes. Then, it was added to a 10 mL reaction bottle containing pyridone (3 mmol, 1.0 eq.) and octyne (6 mmol, 2.0 eq.) with R being H. The reaction mixture was stirred at 90°C for 26 hours. The reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 4:1) to obtain the target compound as a transparent liquid of 467 mg with a calculated yield of 76%.

[0096] NMR data: 1 H NMR (400MHz, CDCl3) δ7.39(d,J=6.96Hz,1H),7.28-7.20(m,1H),7.17(d,J=14.32Hz,1H),6.49(d,J=9.16Hz,1H), 6.12(t,J=6.60Hz,1H),5.76-5.66(m,1H),2.14(q,J=6.60Hz,2H),1.45-1.15(m,8H),0.82(t,J=6.88Hz,3H),ppm.

[0097] 13 C NMR (100MHz, CDCl3) δ161.5,139.4,133.8,126.7,123.5,121.3,106.3,31.5,30.0,29.2,28.7,22.5,14.0ppm.

[0098] Embodiment 9:

[0099] (E)-1-(Hept-1-en-1-yl)pyridin-2(1H)-one

[0100] exist

[0101]

[0102] Under nitrogen atmosphere, a ruthenium catalyst such as Ru(methallyl)2COD (47.9 mg, 0.15 mmol, 5.0 mol%) and a ligand 5-[6-(dibenzo[d,f][1,3,2]dioxaphosphinothiaheptaquinone)]-5H-dibenzo[b,f]azepine (73.7 mg, 0.18 mmol, 6.0 mol%) were dissolved in 6 mL 1,4-dioxane and stirred for 10 minutes. Then, it was added to a 10 mL reaction bottle of pyridone (3 mmol, 1.0 eq) and 1-heptyne (6 mmol, 2.0 eq). The reaction mixture was stirred at 90°C for 26 hours. The reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 4:1) to obtain the target compound as a transparent liquid 418 mg with a calculated yield of 73%.

[0103] NMR data: 1 H NMR (400MHz, CDCl3) δ7.46(d,J=6.88Hz,1H),7.33-7.27(m,1H),7.23(d,J=14.28Hz,1H),6.55(d,J=9.16Hz,1H), 6.18(t,J=6.64Hz,1H),5.81-5.73(m,1H),2.20(q,J=6.96Hz,2H),1.52-1.25(m,6H),0.89(t,J=6.84Hz,3H),ppm.

[0104] 13 C NMR (100MHz, CDCl3) δ161.6,139.3,133.7,126.7,123.6,121.3,106.3,31.3,30.0,29.0,22.4,14.0ppm

[0105] Embodiment 10:

[0106] (E)-1-(Hex-1-en-1-yl)pyridin-2(1H)-one

[0107]

[0108] Under nitrogen atmosphere, a ruthenium catalyst such as Ru(methallyl)2COD (47.9 mg, 0.15 mmol, 5.0 mol%) and a ligand 5-[6-(dibenzo[d,f][1,3,2]dioxaphosphoryl)]-5H-dibenzo[b,f]azepine (73.7 mg, 0.18 mmol, 6.0 mol%) were dissolved in 6 mL 1,4-dioxane and stirred for 10 minutes. Then, it was added to a 10 mL reaction bottle of pyridone (3 mmol, 1.0 eq) and 1-hexyne (6 mmol, 2.0 eq). The reaction mixture was stirred at 90°C for 26 hours. The reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 4:1) to obtain the target compound as a transparent liquid 441 mg with a calculated yield of 83%

[0109] NMR data: 1 H NMR (400MHz, CDCl3) δ7.47(dd,J=6.96Hz,1H),7.35-7.28(m,1H),7.24(d,J=14.32Hz,1H),6.56(d,J=9.16Hz,1H),6 .19(td,J=7.00Hz,1H),5.83-5.74(m,1H),2.22(qd,J=7.36Hz,2H),1.50-1.30(m,4H),0.92(t,J=7.16Hz,3H),ppm.

[0110] 13 C NMR (100MHz, CDCl3) δ161.4,139.3,133.7,126.7,123.4,121.2,106.2,31.3,29.6,22.1,13.8ppm.

[0111] Embodiment 11:

[0112] (E)-1-(3-Phenylprop-1-en-1-yl)pyridin-2(1H)-one

[0113]

[0114] Under nitrogen atmosphere, a ruthenium catalyst such as Ru(methallyl)2COD (47.9 mg, 0.15 mmol, 5.0 mol%) and a ligand 5-[6-(dibenzo[d,f][1,3,2]dioxaphosphinoyl)]-5H-dibenzo[b,f]azepine (73.7 mg, 0.18 mmol, 6.0 mol%) were dissolved in 6 mL 1,4-dioxane and stirred for 10 minutes. Then, it was added to a 10 mL reaction bottle of pyridone (3 mmol, 1.0 eq) and 4-phenyl-1-butyne (6 mmol, 2.0 eq). The reaction mixture was stirred at 90°C for 24 hours. The reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 4:1) to obtain the target compound as a transparent liquid 532 mg with a calculated yield of 84%.

[0115] NMR data: 1 H NMR(400MHz, CDCl3) δ7.39(dd,J=6.96Hz,1H),7.34-7.24(m,4H),7.24-7.16(m,3H),6.55(d,J=9.20H z,1H),6.17(t,J=7.52Hz,1H),5.83-5.73(m,1H),2.79(t,J=7.32Hz,2H),2.53(q,J=6.96Hz,2H),ppm.

[0116] 13 C NMR (100MHz, CDCl3) δ161.3,140.8,139.4,133.6,128.4,128.3,127.2,126.0,122.2,121.2,106.3,35.6,31.7ppm.

[0117] Embodiment 12:

[0118] (E)10-(2-oxopyridin-1(2H)-yl)dec-9-en-1-yl(R)-2-(6-methoxynaphthalen-2-yl)propanoate

[0119]

[0120] Under nitrogen atmosphere, ruthenium catalyst Ru(methallyl)2COD (47.9 mg, 0.15 mmol, 5.0 mol%) and ligand 5-[6-(dibenzo[d,f][1,3,2]dioxaphosphoryl)]-5H-dibenzo[b,f]azepine (73.7 mg, 0.18 mmol, 6.0 mol%) were dissolved in 6 mL 1,4-dioxane and stirred for 10 minutes. Then it was added to a 10 mL reaction bottle containing pyridone (3 mmol, 1.0 eq) with R as H and terminal alkyne (6 mmol, 2.0 eq) with R as naproxen natural product fragment. The reaction mixture was stirred at 90°C for 26 hours. The reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 4:1) to obtain the target compound as a transparent liquid 997 mg with a calculated yield of 65%.

[0121] NMR data: 1 H NMR (400MHz, CDCl3) δ7.62 (t, J=8.6H Z ,3H),7.46-7.39(m,2H),7.33-7.29(m,1H),7.22(d,J=14.3H Z ,1H),7.15-7.11(m,2H),6.56(d,J=9.2H Z ,1H),6.18(t,J=6.5H Z ,1H),5.79-5.71(m,1H),4.06(t,J=6.6H Z ,2H),3.90(s,3H),3.84(dd,J1=14.3H Z ,J2=7.2Hz,1H),2.16(dd,J1=14.1H Z ,J2=7.0Hz,2H),1.58-1.54(m,5H),1.42-1.36(m,2H),1.25-1.20(m,8H),ppm.

[0122] 13 C NMR(100 MHz, CDCl3)δ174.6,161.9,157.5,147.0,140.0,136.6,135.7,133.5,129.1,128.8,127.0,126.1,125 .8,118.8,117.9,112.3,111.0,105.4,64.8,55.1,45.4,29.3(2C),29.1,29.0,28.4,25.7,24.1,18.4 ppm.

Claims

1. A method for synthesizing a trans-N-alkenylpyridine-2(1H)-one compound, characterized in that: Using pyridone compounds and terminal alkyne compounds as raw materials, reacting in an organic solvent in the presence of a ruthenium catalyst and a ligand to obtain a trans-N-alkenylpyridine-2(1H)-one) compound; The structural formula of the pyridone compounds is: The structural formula of terminal acetylenic compounds is: The structural formula of trans-N-alkenylpyridin-2(1H)-one) compounds is: Wherein R1 is one of hydrogen, alkyl, fluorine, chlorine, bromine, methoxy, and ester groups; and R2 is one of aryl, substituted aryl, and alkyl groups.

2. The method for synthesizing trans-N-alkenylpyridine-2(1H)-one compounds according to claim 1, characterized in that: The ruthenium catalyst is one of bis-(2-methylallyl)cycloocta-1,5-dieneruthenium, ruthenium trichloride, bis(tricyclohexylphosphine)benzylideneruthenium dichloride), ruthenium iodide and ruthenium acetate.

3. The method for synthesizing trans-N-alkenylpyridine-2(1H)-one compounds according to claim 1, characterized in that: The organic solvent is one of toluene, xylene, nitrobenzene, chlorobenzene, fluorobenzene, 1,4-dioxane, trifluorotoluene and mesitylene.

4. The method for synthesizing trans-N-alkenylpyridine-2(1H)-one compounds according to claim 1, characterized in that: The ligands are 5-[6-(dibenzo[d,f][1,3,2]dioxaphosphinyl)]-5H-dibenzo[b,f]azepine, bipyridine, (2S,4S)-(-)-2,4-bis(diphenylphosphino)pentane, Xantphos, triisopropylphosphine, triisopropylphosphine, 1,1'-binaphthyl-2,2'-bisdiphenylphosphine (Binap), 1,4-bis(diphenylphosphino)butane (dppb), (6,6'-dimethoxy-[1,1'-biphenyl]-2,2'-diyl)bis(diphenylphosphine), dppf, dppa, 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (Xphos), 2-dicyclohexylphosphino-2',6'-dimethoxy-biphenyl (Sph os), N, N-dimethyl dinaphtho[2,1-d:1',2'-f][1,3,2]dioxaphosphine-4-amine, tricyclohexylphosphine, bis(dicyclohexylphosphino)methane, 1,2-bis(dicyclohexylphosphino)-ethane, 1,3-bis(dicyclohexylphosphino)propane, 1,4-bis(dicyclohexylphosphino)butane.

5. The method for synthesizing trans-N-alkenylpyridine-2(1H)-one compounds according to claim 1, characterized in that: The reaction temperature is 80-120°C, and the reaction time is 15-26h.

6. The method for synthesizing trans-N-alkenylpyridine-2(1H)-one compounds according to claim 1, characterized in that: The equivalent ratio of the ruthenium catalyst, the ligand, the pyridone compound and the terminal acetylene compound is (0.05-0.10):(0.06-0.12):(1):(1-2).

7. The method for synthesizing trans-N-alkenylpyridine-2(1H)-one compounds according to claim 6, characterized in that: The equivalent ratio of the ruthenium catalyst, the ligand, the pyridone compound and the terminal acetylene compound is 0.05:0.06:1:

2.

8. The method for synthesizing trans-N-alkenylpyridine-2(1H)-one compounds according to claim 1, characterized in that: The catalyst is bis-(2-methylallyl)cyclooct-1,5-dieneruthenium; the ligand is 5-[6-(dibenzo[d,f][1,3,2]dioxaphosphoryl)]-5H-dibenzo[b,f]azepine; and the organic solvent is 1,4-dioxane.

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