A method for preparing β-enaminones based on sulfoxides and aldoximes and β-enaminones

Abstract

The present invention provides a method for preparing β-enaminones based on sulfoxides and aldoximes and β-enaminones, relating to the technical field of organic synthesis. In the present invention, an aryl(alkyl)carbonyl heteroaryl sulfoxide, an aldoxime and an organic solvent are mixed for a cycloaddition-intramolecular elimination reaction to obtain β-enaminones. The present invention uses easily available aryl(alkyl)carbonyl heteroaryl sulfoxides as raw materials, and prepares β-enaminone compounds through a series of multi-step reactions including cycloaddition between aryl(alkyl)carbonyl heteroaryl sulfoxides and aldoximes and intramolecular elimination. The operation is simple, the synthetic route is short, and it can be used to synthesize β-enaminone compounds with diverse structures, with a wide substrate scope and universality for the synthesis of β-enaminone compounds. Moreover, the method provided by the present invention can highly selectively obtain β-enaminone compounds. The method provided by the present invention is conducive to the large-scale preparation of β-enaminone compounds.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthesis, and in particular, to a method for preparing β-enaminones based on sulfoxides and aldoximes and β-enaminones. Background Art

[0002] β-Enaminone compounds are a very important class of organic synthesis intermediates and have wide applications in the fields of medicinal chemistry and synthetic chemistry. In medicinal chemistry, it is widely used in the synthesis of antibacterial agents (Y.F. Wang, T. Izawa, S. Kobayashi, M. Ohno, Journal of the American Chemical Society 1982, 104, 6465 - 6466), antispasmodics (J.P. Micheal, C.B. Koning, G.D. Hosken, T.V. Stanbury, Tetrahedron 2001, 57, 9635 - 9648), anticancer agents (D.L. Boger, T. Ishizaki, R.J.W. Jr., S.A. Munk, P.A. Kitos, O. Suntornwat, Journal of the American Chemical Society 1989, 111, 6461 - 6463), etc. As a multifunctional synthon, it is a key intermediate for the synthesis of a series of nitrogen-containing heterocyclic compounds such as pyridine, pyrrole, pyrimidinone, quinoline, etc. (E.O.D. Oliveira, C.A. Brandt, M.A.B.D. Silveira, R.A. Glennon, Tetrahedron Letter 2007, 48, 6393 - 6396; G.J. Reddy, D. Latha, C. Thirupathaiah, K.S. Rao, Tetrahedron Letter 2005, 46, 301 - 302; J. Svetlik, V. Kettmann, B. Zaleska, Tetrahedron Letter 2005, 46, 5511 - 5514.).

[0003] Given the importance of β-enaminones, different preparation methods have been developed successively. Traditional methods include: (1) the acid-catalyzed condensation reaction of 1,3-dicarbonyl compounds with amines (J.-H. Li, S.-L. Xu, C.-P. Li, Synlett 2009, 2009, 818-822; A. Arcadi, G. Bianchi, S.D. Giuseppe, F. Marinelli, Green Chemistry 2003, 5, 64-67); (2) the dehydrogenative acylation reaction of enamides with aldehydes (R.H. Liu, Z.Y. Shen, C. Wang, T.P. Loh, X.H. Hu, Organic Letter 2020, 22, 944-949); (3) the reductive ring-opening of isoxazoles / isoxazolines (C. Wan, J.Y. Pang, W. Jiang, X.W. Zhang, X.G. Hu, Journal of Organic Chemistry 2021, 86:4557-4566; X. Liu, D. Hong, N.G. Sapir, W. Yang, W.H. Hersh, P.H. Leung, D. Yang, Y. Chen, Journal of Organic Chemistry 2019, 84, 16204-16213); (4) the Michael addition reaction of α,β-alkynones with aniline / sulfonamide (X. Zeng, C. Liu, W. Yang, Y. Weng, X. Wang, Y. Hu, Journal of Organic Chemistry 2019, 84:3656-3661; D. Lee, S.M. Kim, H. Hirao, S.H. Hong, Organic Letters 2017, 19:4734-4737; L. Shi, L. Xue, R. Lang, C. Xia, F. Li, ChemCatChem 2014, 6:2560-2566); (5) the decarboxylative coupling reaction of α-ketoacids (X. Kong, Y. Liu, L. Lin, Q. Chen, B. Xu, Green Chemistry 2019, 21:3796-3801; Z. Zhu, X. Tang, J. Li, X. Li, W. Wu, G. Deng, Chemical Communication 2017, 53:3228-3231); (6) the Aldol-type addition of carbonyl compounds to nitriles (H.S.P. Rao, N. Muthanna, European Journal of Organic Chemistry 2015, 2015:1525-1532) or activated isonitriles (J. Kim, S.H.Hong, Chemical Science 2017, 8: 2401 - 2406).

[0004] In the above - mentioned method for preparing β - enaminones, there are problems such as regioselectivity (when an amine reacts with an asymmetric 1,3 - dicarbonyl compound, there is a regioselectivity problem in the reaction with the two carbonyl groups), and difficulties in obtaining raw materials, limited substrate scope, etc. Summary of the Invention

[0005] In view of this, the purpose of the present invention is to provide a method for preparing β - enaminones based on sulfoxides and aldoximes and β - enaminones. The method provided by the present invention can obtain β - enaminones with high selectivity, and the raw materials are easy to obtain and the substrate scope is wide.

[0006] In order to achieve the above - mentioned invention purpose, the present invention provides the following technical solutions:

[0007] The present invention provides a method for preparing β - enaminones based on sulfoxides and aldoximes, comprising the following steps:

[0008] Mix an aryl(alkyl)carbonyl heteroaryl sulfoxide, an aldoxime, and an organic solvent to carry out a cycloaddition - intramolecular elimination reaction to obtain β - enaminones;

[0009] The β - enaminones, aryl(alkyl)carbonyl heteroaryl sulfoxides, and aldoximes have the structures shown in Formulas 1 - 3 in sequence:

[0010]

[0011] In the structures shown in Formulas 1 - 3, R 1 , R 2 and R 3 are independently selected from hydrogen, alkyl, alkoxy, cycloalkyl, cycloalkoxy, cycloalkylalkyl, aryl, substituted aryl, aralkyl, or heteroaryl. The substituents of the substituted aryl include one or more of hydrogen, alkyl, haloalkyl, alkoxy, aryloxy, fluorine, chlorine, bromine, cyano, and nitro, and R 1 and R 3 are not hydrogen.

[0012] Preferably, the alkyl in the alkyl or alkoxy is a straight - chain or branched - chain alkyl with 1 - 15 carbon atoms; the cycloalkyl or cycloalkoxy has 3 - 15 carbon atoms; the cycloalkylalkyl has 4 - 15 carbon atoms; the aryl in the aryl or substituted aryl has 6 - 15 carbon atoms; the heteroaryl has 5 - 15 carbon atoms; the aralkyl has 7 - 15 carbon atoms.

[0013] Preferably, the alkyl group in the alkyl chain or alkoxy group is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, sec-butyl, pentyl, isopentyl, sec-pentyl, neopentyl, hexyl, isohexyl, sec-hexyl, heptyl, isoheptyl, sec-heptyl, octyl, nonyl, decyl, undecyl or dodecyl.

[0014] Preferably, the cycloalkyl group in the cycloalkyl chain or cycloalkoxy group is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl; the cycloalkylalkyl group is cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cycloheptylmethyl, cyclooctylmethyl, cyclopropylethyl, cyclobutylethyl, cyclopentylethyl, cyclohexylethyl, cycloheptylethyl, cyclooctylethyl, cyclopropylpropyl, cyclobutylpropyl, cyclopentylpropyl, cyclohexylpropyl, cycloheptylpropyl or cyclooctylpropyl.

[0015] Preferably, the aryl group in the aryl, substituted aryl or aralkyl group is phenyl, biphenyl or naphthyl; the heteroaryl group is thienyl, furyl or pyridyl.

[0016] Preferably, the substituted aryl group is o-methylphenyl, m-methylphenyl, p-methylphenyl, o-methoxyphenyl, m-methoxyphenyl, p-methoxyphenyl, o-fluorophenyl, m-fluorophenyl, p-fluorophenyl, o-chlorophenyl, m-chlorophenyl, p-chlorophenyl, p-bromophenyl, o-nitrophenyl, m-nitrophenyl, p-nitrophenyl, o-cyanophenyl, m-cyanophenyl, p-cyanophenyl, p-trifluoromethylphenyl, 2,3-dimethoxyphenyl or triphenylethylenephenyl.

[0017] Preferably, the aralkyl group is benzyl, o-methylbenzyl, m-methylbenzyl, p-methylbenzyl, o-methoxybenzyl, m-methoxybenzyl, p-methoxybenzyl, o-fluorobenzyl, m-fluorobenzyl, p-fluorobenzyl, o-chlorobenzyl, m-chlorobenzyl, p-chlorobenzyl, o-nitrobenzyl, m-nitrobenzyl, p-nitrobenzyl, o-cyanobenzyl, m-cyanobenzyl, p-cyanobenzyl, biphenylmethyl, 1-naphthylmethyl, 2-naphthylmethyl, phenethyl, phenylpropyl, phenylbutyl or phenylpentyl.

[0018] Preferably, the β-enaminoketone has any one of the structures shown in Formulas 1a to 1t:

[0019]

[0020] Preferably, the molar ratio of the ar(alk)ylcarbonyl heteroarylsulfoxide to the aldoxime is 3:1 to 1:3; the temperature of the cycloaddition-intramolecular elimination reaction is 20 to 150 °C, and the time is 2 to 8 h.

[0021] The present invention provides a β-enaminoketone having the structure shown in Formula 1q or Formula 1t:

[0022]

[0023] The present invention provides a method for preparing β-enaminones based on sulfoxides and aldoximes, comprising the following steps: mixing an aryl(alkyl)carbonyl heteroaryl sulfoxide, an aldoxime and an organic solvent to carry out a cycloaddition-intramolecular elimination reaction to obtain a β-enaminone. The present invention uses an aryl(alkyl)carbonyl heteroaryl sulfoxide which is simple and readily available as a raw material, and it can be purchased through public commercial channels or prepared by known methods; the present invention prepares β-enaminone compounds in one step through the cycloaddition between an aryl(alkyl)carbonyl heteroaryl sulfoxide and an aldoxime and the intramolecular elimination reaction, with simple operation and a short synthetic route, and it can be used to synthesize β-enaminone compounds with diverse structures, having a wide substrate scope and being universal for the synthesis of β-enaminone compounds; moreover, the method provided by the present invention can avoid the carbonyl selectivity problem existing when an asymmetric 1,3-dicarbonyl compound reacts with an amine, and thus can highly selectively obtain β-enaminone compounds (all are Z-configuration compounds). The method provided by the present invention is conducive to realizing the large-scale preparation of β-enaminone compounds, and has very important significance for the preparation and application of such compounds. Detailed implementation manners

[0024] The present invention provides a method for preparing β-enaminones based on sulfoxides and aldoximes, comprising the following steps:

[0025] Mixing an aryl(alkyl)carbonyl heteroaryl sulfoxide, an aldoxime and an organic solvent to carry out a cycloaddition-intramolecular elimination reaction to obtain a β-enaminone;

[0026] The β-enaminone, aryl(alkyl)carbonyl heteroaryl sulfoxide and aldoxime have the structures shown in Formulas 1 to 3 in sequence:

[0027]

[0028] In the structures shown in Formulas 1 to 3, R 1 , R 2 and R 3 are independently selected from hydrogen, a chain alkyl group, a chain alkoxy group, a cycloalkyl group, a cycloalkoxy group, a cycloalkylalkyl group, an aryl group, a substituted aryl group, an aralkyl group or a heteroaryl group, the substituents of the substituted aryl group include one or more of hydrogen, an alkyl group, a haloalkyl group, an alkoxy group, an aryloxy group, fluorine, chlorine, bromine, a cyano group and a nitro group, and R 1 and R 3 are not hydrogen.

[0029] In the present invention, the alkyl group in the alkyl chain or alkoxy group is preferably a straight-chain or branched-chain alkyl group having 1 to 15 carbon atoms, more preferably a straight-chain or branched-chain alkyl group having 1 to 12 carbon atoms, still more preferably a straight-chain or branched-chain alkyl group having 3 to 10 carbon atoms, and most preferably a straight-chain or branched-chain alkyl group having 3 to 8 carbon atoms. In the examples of the present invention, the alkyl group in the alkyl chain or alkoxy group is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, sec-butyl, pentyl, isopentyl, sec-pentyl, neopentyl, hexyl, isohexyl, sec-hexyl, heptyl, isoheptyl, sec-heptyl, octyl, nonyl, decyl, undecyl or dodecyl.

[0030] In the present invention, the number of carbon atoms of the cycloalkyl group or cycloalkoxy group is preferably 3 to 15; the cycloalkyl group in the cycloalkyl group or cycloalkoxy group is more preferably cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl, and still more preferably cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl.

[0031] In the present invention, the number of carbon atoms of the cycloalkylalkyl group is preferably 4 to 15; the cycloalkylalkyl group is more preferably cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cycloheptylmethyl, cyclooctylmethyl, cyclopropylethyl, cyclobutylethyl, cyclopentylethyl, cyclohexylethyl, cycloheptylethyl, cyclooctylethyl, cyclopropylpropyl, cyclobutylpropyl, cyclopentylpropyl, cyclohexylpropyl, cycloheptylpropyl or cyclooctylpropyl, and still more preferably cyclopropylmethyl, cyclopentylmethyl, cyclohexylmethyl, cycloheptylmethyl, cyclopropylethyl, cyclopentylethyl, cyclohexylethyl, cycloheptylethyl, cyclopropylpropyl, cyclopentylpropyl, cyclohexylpropyl or cycloheptylpropyl.

[0032] In the present invention, the number of carbon atoms of the aryl group or substituted aryl group is preferably 6 to 15; the number of carbon atoms of the aralkyl group is preferably 7 to 15. In the present invention, the aryl group in the aryl group, substituted aryl group or aralkyl group is more preferably phenyl, biphenyl or naphthyl, and the naphthyl group is preferably 1-naphthyl or 2-naphthyl.

[0033] In the present invention, the substituents of the substituted aryl group include one or more of hydrogen, alkyl, alkoxy, aryloxy, fluorine, chlorine, bromine, cyano and nitro. In the present invention, the substituted aryl group is further preferably o-methylphenyl, m-methylphenyl, p-methylphenyl, o-methoxyphenyl, m-methoxyphenyl, p-methoxyphenyl, o-fluorophenyl, m-fluorophenyl, p-fluorophenyl, o-chlorophenyl, m-chlorophenyl, p-chlorophenyl, p-bromophenyl, o-nitrophenyl, m-nitrophenyl, p-nitrophenyl, o-cyanophenyl, m-cyanophenyl, p-cyanophenyl, p-trifluoromethylphenyl, 2,3-dimethoxyphenyl or triphenylethylenephenyl.

[0034] In the present invention, the aralkyl group is more preferably benzyl, o-methylbenzyl, m-methylbenzyl, p-methylbenzyl, o-methoxybenzyl, m-methoxybenzyl, p-methoxybenzyl, o-fluorobenzyl, m-fluorobenzyl, p-fluorobenzyl, o-chlorobenzyl, m-chlorobenzyl, p-chlorobenzyl, o-nitrobenzyl, m-nitrobenzyl, p-nitrobenzyl, o-cyanobenzyl, m-cyanobenzyl, p-cyanobenzyl, biphenylmethyl, 1-naphthylmethyl, 2-naphthylmethyl, phenethyl, phenylpropyl, phenylbutyl or phenylpentyl.

[0035] In the present invention, the heteroaryl group preferably has 5 to 15 carbon atoms, and the heteroaryl group is further preferably thienyl, furyl or pyridyl.

[0036] As an embodiment of the present invention, R 1 Specifically selects one of the following groups: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, sec-butyl, pentyl, isopentyl, sec-pentyl, neopentyl, hexyl, isohexyl, sec-hexyl, heptyl, isoheptyl, sec-heptyl, octyl, nonyl, decyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, phenyl, p-tolyl, p-chlorophenyl, p-bromophenyl, p-fluorophenyl, m-fluorophenyl, p-nitrophenyl, p-cyanophenyl, p-methoxyphenyl, p-trifluoromethylphenyl, biphenyl, benzyl, o-methylbenzyl, m-methylbenzyl, p-methylbenzyl, o-methoxybenzyl, m-methoxybenzyl, p-methoxybenzyl, o-fluorobenzyl, m-fluorobenzyl, p-fluorobenzyl, o-chlorobenzyl, m-chlorobenzyl, p-chlorobenzyl, o-nitrobenzyl, m-nitrobenzyl, p-nitrobenzyl, o-cyanobenzyl, m-cyanobenzyl, p-cyanobenzyl, biphenylmethyl, 1-naphthylmethyl, 2-naphthylmethyl, phenethyl, phenylpropyl, phenylbutyl, phenylpentyl, thienyl, and is more preferably phenyl, p-fluorophenyl, m-fluorophenyl, p-chlorophenyl, p-bromophenyl, p-nitrophenyl, p-cyanophenyl, p-trifluoromethylphenyl, p-tolyl, biphenyl or thienyl.

[0037] As an embodiment of the present invention, the R 2Specifically selected from one of the following groups: hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, sec-butyl, pentyl, isopentyl, sec-pentyl, neopentyl, hexyl, isohexyl, sec-hexyl, heptyl, isoheptyl, sec-heptyl, octyl, nonyl, decyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, phenyl, p-tolyl, p-chlorophenyl, p-bromophenyl, p-fluorophenyl, p-nitrophenyl, p-methoxyphenyl, benzyl, o-methylbenzyl, m-methylbenzyl, p-methylbenzyl, o-methoxybenzyl, m-methoxybenzyl, p-methoxybenzyl, o-fluorobenzyl, m-fluorobenzyl, p-fluorobenzyl, o-chlorobenzyl, m-chlorobenzyl, p-chlorobenzyl, o-nitrobenzyl, m-nitrobenzyl, p-nitrobenzyl, o-cyanobenzyl, m-cyanobenzyl, p-cyanobenzyl, biphenylmethyl, 1-naphthylmethyl, 2-naphthylmethyl, phenethyl, phenylpropyl, phenylbutyl, phenylpentyl.

[0038] As an embodiment of the present invention, the R 3 Specifically selected from one of the following groups: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, sec-butyl, pentyl, isopentyl, sec-pentyl, neopentyl, hexyl, isohexyl, sec-hexyl, heptyl, isoheptyl, sec-heptyl, octyl, nonyl, decyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, phenyl, p-tolyl, p-chlorophenyl, p-bromophenyl, p-fluorophenyl, o-fluorophenyl, m-fluorophenyl, p-nitrophenyl, p-methoxyphenyl, benzyl, o-methylbenzyl, m-methylbenzyl, p-methylbenzyl, o-methoxybenzyl, m-methoxybenzyl, p-methoxybenzyl, 2,3-dimethoxyphenyl, o-fluorobenzyl, m-fluorobenzyl, p-fluorobenzyl, o-chlorobenzyl, m-chlorobenzyl, p-chlorobenzyl, o-nitrobenzyl, m-nitrobenzyl, p-nitrobenzyl, o-cyanobenzyl, m-cyanobenzyl, p-cyanobenzyl, biphenylmethyl, naphthyl, 1-naphthylmethyl, 2-naphthylmethyl, phenethyl, phenylpropyl, phenylbutyl, phenylpentyl, triphenylvinylphenyl, more preferably phenyl, p-fluorophenyl, o-fluorophenyl, m-fluorophenyl, p-chlorophenyl, p-nitrophenyl, naphthyl, benzyl or triphenylvinylphenyl.

[0039] The present invention has no particular requirements on the sources of the aryl(alkyl)carbonyl heteroaryl sulfoxide and the aldoxime, and they can be commercial products or prepared by methods well-known to those skilled in the art, such as prepared according to the methods in existing literature. Among them, the aryl(alkyl)carbonyl heteroaryl sulfoxide can be prepared referring to the literature "Facile Synthesis of Quinoxaline-2-thiol and Quinoxaline from α-Oxosulfines and o-Arylenediamines" (Synthesis 54(11):2616-2628).

[0040] In the present invention, the molar ratio of the aryl(alkyl)formyl heteroarylsulfoxide to the aldoxime is preferably 3:1 to 1:3, more preferably 1:1.5; the organic solvent preferably includes one or more of 1,4-dioxane, tetrahydrofuran, 2-methyltetrahydrofuran, dimethyl sulfoxide, cyclobutyl sulfoxide, dimethyl sulfone, sulfolane, acetonitrile, propionitrile, butyronitrile, valeronitrile, methanol, ethanol, propanol, isopropanol, butanol, isobutanol, dichloromethane, chloroform, carbon tetrachloride, dichloroethane, trichloroethane, tetrachloroethane, tetrachloroethylene and dichlorobenzene, and more preferably ethanol. There is no particular requirement for the amount of the organic solvent in the present invention, and it is only necessary to ensure the smooth progress of the reaction. In the present invention, the aryl(alkyl)formyl heteroarylsulfoxide and the aldoxime are preferably added to a reaction vessel, and then the organic solvent is added thereto. In the present invention, the temperature of the cycloaddition-intramolecular elimination reaction is preferably 20 to 150 °C, more preferably 50 to 100 °C, and further preferably 80 °C, and the time is preferably 2 to 8 h, more preferably 3 to 6 h, and further preferably 4 h; when the temperature of the cycloaddition-intramolecular elimination reaction needs to be achieved by heating, steam heating, electric heating or microwave heating can be used. In the present invention, the reaction formula involved in the cycloaddition-intramolecular elimination reaction is as follows:

[0041]

[0042] After the cycloaddition-intramolecular elimination reaction is completed, in the present invention, the obtained reaction solution is preferably rotary evaporated and then subjected to column chromatography separation and concentration to obtain β-enaminone. In the present invention, the eluent used for the column chromatography separation is preferably a mixed reagent of petroleum ether and ethyl acetate, and the volume ratio of the petroleum ether to the ethyl acetate is preferably 20:1.

[0043] As an embodiment of the present invention, the β-enaminone has any one of the structures shown in Formulas 1a to 1t:

[0044] The corresponding substituents of the above-mentioned β-enaminone (denoted as Compounds 1a to 1t) corresponding to the structure of Formula 1 are as follows:

[0045] Compound 1a: R 1 = Ph, R 2 = H, R 3 = Ph;

[0046] Compound 1b: R 1 = 4-FC6H4, R 2 = H, R 3 = Ph;

[0047] Compound 1c: R 1 = 3-FC6H4, R2 = H, R 3 = Ph;

[0048] Compound 1d: R 1 = 4-ClC6H4, R 2 = H, R 3 = Ph;

[0049] Compound 1e: R 1 = 4-BrC6H4, R 2 = H, R 3 = Ph;

[0050] Compound 1f: R 1 = 4-NO2C6H4, R 2 = H, R 3 = Ph;

[0051] Compound 1g: R 1 = 4-CNC6H4, R 2 = H, R 3 = Ph;

[0052] Compound 1h: R 1 = 4-CF3C6H4, R 2 = H, R 3 = Ph;

[0053] Compound 1i: R 1 = 4-MeC6H4, R 2 = H, R 3 = Ph;

[0054] Compound 1j: R 1 = 4-PhC6H4, R 2 = H, R 3 = Ph;

[0055] Compound 1k: R 1 = Thiophen-2-yl, R 2 = H, R 3 = Ph;

[0056] Compound 1l: R 1 = Ph, R 2 = H, R 3 = 4-FC6H4;

[0057] Compound 1m: R 1 = Ph, R 2 = H, R 3 = 3-FC6H4;

[0058] Compound 1n: R 1 = Ph, R2 = H, R 3 = 2-FC6H4;

[0059] Compound 1o: R 1 = Ph, R 2 = H, R 3 = 4-ClC6H4;

[0060] Compound 1p: R 1 = Ph, R 2 = H, R 3 = 4-NO2C6H4;

[0061] Compound 1q: R 1 = Ph, R 2 = H, R 3 = 2,3-OMeC6H3;

[0062] Compound 1r: R 1 = Ph, R 2 = H, R 3 = 2-Naphthyl;

[0063] Compound 1s: R 1 = Ph, R 2 = H, R 3 = Benzyl;

[0064] Compound 1t: R 1 = Ph, R 2 = H, R 3 = 4-(Triphenylvinyl)phenyl.

[0065] The present invention obtains β-enaminone compounds through the direct cycloaddition and intramolecular elimination reaction of aryl(alkyl)formyl heteroaryl sulfoxides with aldoximes. The β-enaminone compounds prepared by the present invention are very important organic synthesis intermediates and have wide applications in both the fields of medicinal chemistry and synthetic chemistry. In medicinal chemistry, the enaminone compounds (arylamine enaminone compounds) prepared by the present invention have very wide pharmacological activities, having the effects of anti-convulsion, anti-malaria, anti-virus and treating cardiovascular diseases, and can be used for the preparation of related drugs.

[0066] The present invention provides a β-enaminone having the structure shown in Formula 1q or Formula 1t:

[0067]

[0068] The β-enaminone provided by the present invention has the same uses as above and will not be elaborated here.

[0069] To further illustrate the present invention, the method for preparing β-enaminone based on sulfoxide and aldoxime and β-enaminone provided by the present invention will be described in detail below with reference to examples, but they should not be construed as limiting the scope of protection of the present invention.

[0070] Example 1

[0071] (2Z)-3-Amino-1,3-diphenylprop-2-en-1-one (Compound 1a)

[0072] 2-((1-Methyl-1H-tetrazol-5-yl)sulfinyl)-1-phenylethan-1-one (0.20 mmol, 50 mg) and benzaldoxime (0.30 mmol, 36 mg) were added to a 10 mL reaction tube, 0.5 mL of ethanol was added, and the reaction was carried out at 80 °C for 4 hours. After cooling, it was rotary evaporated to dryness, and separated by column chromatography (eluent: V(petroleum ether):V(ethyl acetate) = 20:1), and after concentration, (2Z)-3-amino-1,3-diphenylprop-2-en-1-one was obtained as a golden yellow liquid, 35 mg, yield 79%. 1 HNMR(400 MHz, CDCl3): δ = 10.41(br s, 1H), 7.97–7.91(m, 2H), 7.71–7.60(m, 2H), 7.55–7.39(m, 6H), 6.14(s, 1H), 5.53(br s, 1H). 13 C NMR(101 MHz, CDCl3): δ = 190.2, 163.0, 140.3, 137.6, 131.1, 130.8, 129.1, 128.3, 127.3, 126.4, 91.9.

[0073] Example 2

[0074] (2Z)-3-Amino-1-(4-fluorophenyl)-3-phenylprop-2-en-1-one (Compound 1b)

[0075] 1-(4-Fluorophenyl)-2-((1-methyl-1H-tetrazol-5-yl)sulfinyl)ethan-1-one (0.20 mmol, 54 mg) and benzaldoxime (0.30 mmol, 36 mg) were added to a 10 mL reaction tube, 0.5 mL of ethanol was added, and the reaction was carried out at 80 °C for 4 hours. After cooling, it was rotary evaporated to dryness, and separated by column chromatography (eluent: V(petroleum ether):V(ethyl acetate) = 20:1), and after concentration, (2Z)-3-amino-1-(4-fluorophenyl)-3-phenylprop-2-en-1-one was obtained as a golden yellow solid, 20 mg, yield 42%. 11H NMR (400 MHz, CDCl3): δ = 10.29 (br s, 1H), 7.91–7.81 (m, 2H), 7.58–7.49 (m, 2H), 7.43–7.32 (m, 3H), 7.00 (t, J = 8.7 Hz, 2H), 5.98 (s, 1H), 5.56 (br s, 1H). 13 13C NMR (101 MHz, CDCl3): δ = 188.5, 164.5 (d, J F-C = 251.0 Hz), 163.1, 137.3, 136.4 (d, J F-C = 3.0 Hz), 130.7, 129.4 (d, J F-C = 8.9 Hz), 129.0, 126.3, 115.1 (d, J F-C = 21.6 Hz), 91.3. 19 19F NMR (376 MHz, CDCl3) δ -109.18.

[0076] Example 3

[0077] (2Z)-3-Amino-1-(3-fluorophenyl)-3-phenylprop-2-en-1-one (Compound 1c)

[0078] 1-(3-Fluorophenyl)-2-((1-methyl-1H-tetrazol-5-yl)sulfinyl)ethan-1-one (0.20 mmol, 54 mg) and benzaldehyde oxime (0.30 mmol, 36 mg) were added to a 10 mL reaction tube, 0.5 mL of ethanol was added, and the reaction was carried out at 80 °C for 4 hours. After cooling, it was rotary evaporated to dryness, and separated by column chromatography (eluent: V(petroleum ether):V(ethyl acetate) = 20:1), and after concentration, (2Z)-3-amino-1-(3-fluorophenyl)-3-phenylprop-2-en-1-one was obtained as a yellow oily liquid, 23 mg, yield 47%. 1 1H NMR (400 MHz, CDCl3): δ = 10.43 (br s, 1H), 7.71 (dt, J = 7.8, 1.2 Hz, 1H), 7.66–7.59 (m, 3H), 7.56–7.44 (m, 3H), 7.39 (td, J = 7.9, 5.6 Hz, 1H), 7.19–7.11 (m, 1H), 6.08 (s, 1H), 5.65 (br s, 1H). 13 13C NMR (101 MHz, CDCl3): δ = 188.4, 163.6, 162.9 (d, J F-C = 246.3 Hz), 142.6 (d, J F-C= 6.2 Hz), 137.3, 131.0, 129.9 (d, J F-C = 7.7 Hz), 129.1, 126.4, 122.8 (d, J F-C = 2.8 Hz), 117.9 (d, J F-C = 21.5 Hz), 114.1 (d, J F-C = 22.2 Hz), 91.6. 19 F NMR (376 MHz, CDCl3) δ -112.9.

[0079] Example 4

[0080] (2Z)-3-Amino-1-(4-chlorophenyl)-3-phenylprop-2-en-1-one (Compound 1d)

[0081] 1-(4-Chlorophenyl)-2-((1-methyl-1H-tetrazol-5-yl)sulfinyl)ethan-1-one (0.20 mmol, 57 mg) and benzaldehyde oxime (0.30 mmol, 36 mg) were added to a 10 mL reaction tube, 0.5 mL of ethanol was added, and the reaction was carried out at 80 °C for 4 hours. After cooling, it was evaporated to dryness, separated by column chromatography (the eluent was V(petroleum ether):V(ethyl acetate) = 20:1), and after concentration, (2Z)-3-amino-1-(4-chlorophenyl)-3-phenylprop-2-en-1-one was obtained as a yellow oily liquid, 33 mg, yield 65%. 1 H NMR (400 MHz, CDCl3): δ = 10.41 (br s, 1H), 7.91–7.83 (m, 2H), 7.68–7.58 (m, 2H), 7.55–7.41 (m, 3H), 7.39 (d, J = 8.5 Hz, 2H), 6.08 (s, 1H), 5.63 (br s, 1H). 13 C NMR (101 MHz, CDCl3): δ = 188.6, 163.5, 138.6, 137.4, 137.2, 130.9, 129.1, 128.7, 128.5, 126.4, 91.5.

[0082] Example 5

[0083] (2Z)-3-Amino-1-(4-bromophenyl)-3-phenylprop-2-en-1-one (Compound 1e)

[0084] 1-(4-Bromophenyl)-2-((1-methyl-1H-tetrazol-5-yl)sulfinyl)ethan-1-one (0.20 mmol, 66 mg) and benzaldehyde oxime (0.30 mmol, 36 mg) were added to a 10 mL reaction tube, 0.5 mL of ethanol was added, and the reaction was carried out at 80 °C for 4 hours. After cooling, it was concentrated by evaporation, and separated by column chromatography (eluent: V(petroleum ether):V(ethyl acetate) = 20:1). After concentration, (2Z)-3-amino-1-(4-bromophenyl)-3-phenylprop-2-en-1-one was obtained as a yellow oily liquid, 36 mg, yield 60%. 1 H NMR (400 MHz, CDCl3): δ = 10.42 (br s, 1H), 7.84–7.77 (m, 2H), 7.65–7.60 (m, 2H), 7.57–7.53 (m, 2H), 7.52–7.43 (m, 3H), 6.07 (s, 1H), 5.62 (br s, 1H). 13 C NMR (101 MHz, CDCl3): δ = 188.7, 163.5, 139.1, 137.3, 131.5, 130.9, 129.1, 128.9, 126.4, 125.7, 91.5.

[0085] Example 6

[0086] (2Z)-3-Amino-1-(4-nitrophenyl)-3-phenylprop-2-en-1-one (Compound 1f)

[0087] 1-(4-Nitrophenyl)-2-((1-methyl-1H-tetrazol-5-yl)sulfinyl)ethan-1-one (0.20 mmol, 59 mg) and benzaldehyde oxime (0.30 mmol, 36 mg) were added to a 10 mL reaction tube, 0.5 mL of ethanol was added, and the reaction was carried out at 80 °C for 4 hours. After cooling, it was concentrated by evaporation, and separated by column chromatography (eluent: V(petroleum ether):V(ethyl acetate) = 20:1). After concentration, (2Z)-3-amino-1-(4-nitrophenyl)-3-phenylprop-2-en-1-one was obtained as a golden solid, 13 mg, yield 25%. 1 H NMR (400 MHz, CDCl3): δ = 10.57 (br s, 1H), 8.28 (d, J = 8.8 Hz, 2H), 8.07 (d, J = 8.8 Hz, 2H), 7.68–7.63 (m, 3H), 7.60–7.46 (m, 2H), 6.13 (s, 1H), 5.74 (s, 1H). 1313C NMR (101 MHz, CDCl3): δ = 187.3, 164.5, 149.1, 145.7, 136.9, 131.3, 129.3, 128.2, 126.4, 123.6, 91.9.

[0088] Example 7

[0089] (2Z)-3-Amino-1-(4-cyanophenyl)-3-phenylprop-2-en-1-one (Compound 1g)

[0090] 1-(4-Cyanophenyl)-2-((1-methyl-1H-tetrazol-5-yl)sulfinyl)ethan-1-one (0.20 mmol, 55 mg) and benzaldehyde oxime (0.30 mmol, 36 mg) were added to a 10 mL reaction tube, 0.5 mL of ethanol was added, and the reaction was carried out at 80 °C for 4 hours. After cooling, it was evaporated to dryness, separated by column chromatography (eluent: V(petroleum ether):V(ethyl acetate) = 20:1), and concentrated to obtain (2Z)-3-amino-1-(4-cyanophenyl)-3-phenylprop-2-en-1-one, a golden solid, 33 mg, yield 67%. 1 1H NMR (400 MHz, CDCl3): δ = 10.53 (br s, 1H), 8.00 (d, J = 8.1 Hz, 2H), 7.71 (d, J = 8.1 Hz, 2H), 7.66–7.61 (m, 2H), 7.57–7.45 (m, 3H), 6.09 (s, 1H), 5.84 (s, 1H). 13 13C NMR (101 MHz, CDCl3): δ = 187.5, 164.3, 143.9, 136.8, 132.1, 131.1, 129.1, 127.6, 126.3, 118.5, 114.0, 91.6.

[0091] Example 8

[0092] (2Z)-3-Amino-1-(4-trifluoromethylphenyl)-3-phenylprop-2-en-1-one (Compound 1h)

[0093] 1-(4-Trifluoromethylphenyl)-2-((1-methyl-1H-tetrazol-5-yl)sulfinyl)ethan-1-one (0.20 mmol, 64 mg) and benzaldehyde oxime (0.30 mmol, 36 mg) were added to a 10 mL reaction tube, 0.5 mL of ethanol was added, and the reaction was carried out at 80 °C for 4 hours. After cooling, it was rotary evaporated to dryness, and separated by column chromatography (eluent: V(petroleum ether):V(ethyl acetate) = 20:1), and after concentration, (2Z)-3-amino-1-(4-trifluoromethylphenyl)-3-phenylprop-2-en-1-one, a white solid, 36 mg, yield 62%. 1 H NMR (400 MHz, CDCl3): δ = 10.49 (br s, 1H), 8.01 (d, J = 8.1 Hz, 2H), 7.68 (d, J = 8.1 Hz, 2H), 7.64–7.61 (m, 2H), 7.55–7.44 (m, 3H), 6.11 (s, 1H), 5.75 (br s, 1H). 13 C NMR (101 MHz, CDCl3): δ = 188.5, 164.0, 143.4, 137.1, 132.41 (q, J F-C = 32.4 Hz), 131.1, 129.2, 127.5, 126.4, 125.32 (q, J F-C = 3.7 Hz), 123.98 (q, J F-C = 272.4 Hz), 91.8. 19 F NMR (376 MHz, CDCl3) δ -62.71.

[0094] Example 9

[0095] (2Z)-3-Amino-1-(4-methylphenyl)-3-phenylprop-2-en-1-one (Compound 1i)

[0096] 1-(4-Methylphenyl)-2-((1-methyl-1H-tetrazol-5-yl)sulfinyl)ethan-1-one (0.20 mmol, 53 mg) and benzaldehyde oxime (0.30 mmol, 36 mg) were added to a 10 mL reaction tube, 0.5 mL of ethanol was added, and the reaction was carried out at 80 °C for 4 hours. After cooling, it was rotary evaporated to dryness, and separated by column chromatography (eluent: V(petroleum ether):V(ethyl acetate) = 20:1), and after concentration, (2Z)-3-amino-1-(4-methylphenyl)-3-phenylprop-2-en-1-one, a yellow oil, 27 mg, yield 57%. 11H NMR (400 MHz, CDCl3): δ = 10.37 (br s, 1H), 7.85 (d, J = 8.1 Hz, 2H), 7.70–7.56 (m, 2H), 7.52–7.40 (m, 3H), 7.23 (d, J = 7.9 Hz, 2H), 6.13 (s, 1H), 5.45 (br s, 1H), 2.39 (s, 3H). 13 13C NMR (101 MHz, CDCl3): δ = 190.0, 162.6, 141.5, 137.7, 137.7, 130.6, 129.0, 127.3, 126.4, 91.8, 21.5.

[0097] Example 10

[0098] (2Z)-3-Amino-3-phenyl-1-(4-phenylphenyl)prop-2-en-1-one (Compound 1j)

[0099] 1-(4-Phenylphenyl)-2-((1-methyl-1H-tetrazol-5-yl)sulfinyl)ethan-1-one (0.20 mmol, 65 mg) and benzaldehyde oxime (0.30 mmol, 36 mg) were added to a 10 mL reaction tube, 0.5 mL of ethanol was added, and the reaction was carried out at 80 °C for 4 hours. After cooling, it was evaporated to dryness, separated by column chromatography (eluent: V(petroleum ether):V(ethyl acetate) = 20:1), and concentrated to obtain (2Z)-3-amino-3-phenyl-1-(4-phenylphenyl)prop-2-en-1-one, a yellow solid, 47 mg, yield 79%. 1 1H NMR (400 MHz, CDCl3): δ = 10.44 (br s, 1H), 8.06–7.98 (m, 2H), 7.69–7.59 (m, 6H), 7.52–7.42 (m, 5H), 7.39–7.33 (m, 1H), 6.19 (s, 1H), 5.55 (br s, 1H). 13 13C NMR (101 MHz, CDCl3): δ = 189.6, 162.9, 143.7, 140.3, 139.0, 137.5, 130.7, 129.0, 128.8, 127.7, 127.2, 126.9, 126.3, 91.8.

[0100] Example 11

[0101] (2Z)-3-Amino-3-phenyl-1-(thiophen-2-yl)prop-2-en-1-one (Compound 1k)

[0102] 1-(2-Thienyl)-2-((1-methyl-1H-tetrazol-5-yl)sulfinyl)ethan-1-one (0.20 mmol, 51 mg) and benzaldoxime (0.30 mmol, 36 mg) were added to a 10 mL reaction tube, 0.5 mL of ethanol was added, and the reaction was carried out at 80 °C for 4 hours. After cooling, the solvent was evaporated under reduced pressure, and the residue was separated by column chromatography (eluent: V(petroleum ether):V(ethyl acetate) = 20:1). After concentration, (2Z)-3-amino-3-phenyl-1-(thiophen-2-yl)prop-2-en-1-one was obtained as a yellow solid, 35 mg, yield 77%. 1 H NMR (400 MHz, CDCl3): δ = 10.13 (br s, 1H), 7.70–7.60 (m, 3H), 7.55–7.44 (m, 4H), 7.10 (dd, J = 4.9, 3.7 Hz, 1H), 6.02 (s, 1H), 5.41 (br s, 1H). 13 C NMR (101 MHz, CDCl3): δ = 182.8, 162.6, 147.1, 137.3, 130.8, 130.7, 129.1, 128.2, 127.8, 126.3, 91.6.

[0103] Example 12

[0104] (2Z)-3-Amino-3-(4-fluorophenyl)-1-phenylprop-2-en-1-one (Compound 1l)

[0105] 2-((1-Methyl-1H-tetrazol-5-yl)sulfinyl)-1-phenylethan-1-one (0.20 mmol, 50 mg) and 4-fluorobenzaldoxime (0.30 mmol, 42 mg) were added to a 10 mL reaction tube, 0.5 mL of ethanol was added, and the reaction was carried out at 80 °C for 4 hours. After cooling, the solvent was evaporated under reduced pressure, and the residue was separated by column chromatography (eluent: V(petroleum ether):V(ethyl acetate) = 20:1). After concentration, (2Z)-3-amino-3-(4-fluorophenyl)-1-phenylprop-2-en-1-one was obtained as a yellow liquid, 26 mg, yield 54%. 1 HNMR (400 MHz, CDCl3): δ = 10.40 (br s, 1H), 7.97–7.90 (m, 2H), 7.68–7.59 (m, 2H), 7.54–7.39 (m, 3H), 7.20–7.10 (m, 2H), 6.09 (s, 1H), 5.46 (br s, 1H). 13 C NMR (101 MHz, CDCl3): δ = 190.2, 164.16 (d, J F-C= 251.1 Hz), 161.8, 140.2, 133.72 (d, J F-C = 3.3 Hz), 131.2, 128.43 (d, J F-C = 8.5 Hz), 128.34, 127.22, 116.14 (d, J F-C = 21.8 Hz), 91.95. 19 19F NMR (376 MHz, CDCl3) δ -109.32.

[0106] Example 13

[0107] (2Z)-3-Amino-3-(3-fluorophenyl)-1-phenylprop-2-en-1-one (Compound 1m)

[0108] 2-((1-Methyl-1H-tetrazol-5-yl)sulfinyl)-1-phenylethan-1-one (0.20 mmol, 50 mg) and 3-fluorobenzaldoxime (0.30 mmol, 42 mg) were added to a 10 mL reaction tube, 0.5 mL of ethanol was added, and the reaction was carried out at 80 °C for 4 hours. After cooling, it was evaporated to dryness, and separated by column chromatography (eluent: V(petroleum ether):V(ethyl acetate) = 20:1), and after concentration, (2Z)-3-amino-3-(3-fluorophenyl)-1-phenylprop-2-en-1-one was obtained as a yellow liquid, 14 mg, yield 29%. 1 1H NMR (400 MHz, CDCl3): δ = 10.34 (br s, 1H), 8.10–7.84 (m, 2H), 7.59–7.39 (m, 5H), 7.37–7.30 (m, 1H), 7.23–7.13 (m, 1H), 6.11 (s, 1H), 5.55 (br s, 1H). 13 13C NMR (101 MHz, CDCl3): δ = 190.4, 162.9 (d, J F-C = 247.6 Hz), 161.4 (d, J F-C = 2.2 Hz), 140.0, 139.8 (d, J F-C = 7.5 Hz), 131.3, 130.8 (d, J F-C = 8.3 Hz), 128.4, 127.3, 122.1 (d, J F-C = 3.0 Hz), 117.6 (d, J F-C = 21.1 Hz), 113.7 (d, J F-C = 22.8 Hz), 92.1. 19 19F NMR (376 MHz, CDCl3) δ -111.40.

[0109] Example 14

[0110] (2Z)-3-Amino-3-(2-fluorophenyl)-1-phenylprop-2-en-1-one (Compound 1n)

[0111] 2-((1-Methyl-1H-tetrazol-5-yl)sulfinyl)-1-phenylethan-1-one (0.20 mmol, 50 mg) and 2-fluorobenzaldoxime (0.30 mmol, 42 mg) were added to a 10 mL reaction tube, 0.5 mL of ethanol was added, and the reaction was carried out at 80 °C for 4 hours. After cooling, it was concentrated by rotary evaporation and separated by column chromatography (eluent: V(petroleum ether):V(ethyl acetate) = 20:1). After concentration, (2Z)-3-amino-3-(2-fluorophenyl)-1-phenylprop-2-en-1-one was obtained as a yellow liquid, 29 mg, yield 61%. 1 HNMR(400MHz,CDCl3):δ=10.31(br s,1H),8.39–8.30(m,2H),8.04–7.90(m,2H),7.88–7.78(m,2H),7.56–7.42(m,3H),6.16(s,1H),5.35(s,1H). 13 C NMR(101MHz,CDCl3):δ=190.4,159.76(d,J F-C =251.3Hz),158.2,140.2,131.97(d,J F-C =8.7Hz),131.2,129.46(d,J F-C =2.7Hz),129.04(d,J F-C =61.8Hz),128.3,127.3,124.91(d,J F-C =12.0Hz),124.76(d,J F-C =3.6Hz),116.70(d,J F-C =22.4Hz),93.49(d,J F-C =2.3Hz).

[0112] Example 15

[0113] (2Z)-3-Amino-3-(4-chlorophenyl)-1-phenylprop-2-en-1-one (Compound 1o)

[0114] 2-((1-Methyl-1H-tetrazol-5-yl)sulfinyl)-1-phenylethan-1-one (0.20 mmol, 50 mg) and 4-chlorobenzaldoxime (0.30 mmol, 47 mg) were added to a 10 mL reaction tube, 0.5 mL of ethanol was added, and the reaction was carried out at 80 °C for 4 hours. After cooling, the solvent was evaporated under reduced pressure, and the product was separated by column chromatography (eluent: V(petroleum ether):V(ethyl acetate) = 20:1). After concentration, (2Z)-3-amino-3-(4-chlorophenyl)-1-phenylprop-2-en-1-one was obtained as a golden solid, 26 mg, yield 51%. 1 1H NMR (400 MHz, CDCl3): δ = 10.36 (br s, 1H), 8.05–7.79 (m, 2H), 7.59–7.54 (m, 2H), 7.51–7.39 (m, 5H), 6.09 (s, 1H), 5.49 (br s, 1H). 13 13C NMR (101 MHz, CDCl3): δ = 190.3, 161.6, 140.1, 136.8, 136.0, 131.3, 129.3, 128.4, 127.8, 127.2, 92.0.

[0115] Example 16

[0116] (2Z)-3-Amino-3-(4-nitrophenyl)-1-phenylprop-2-en-1-one (Compound 1p)

[0117] 2-((1-Methyl-1H-tetrazol-5-yl)sulfinyl)-1-phenylethan-1-one (0.20 mmol, 50 mg) and 4-nitrobenzaldoxime (0.30 mmol, 50 mg) were added to a 10 mL reaction tube, 0.5 mL of ethanol was added, and the reaction was carried out at 80 °C for 4 hours. After cooling, the solvent was evaporated under reduced pressure, and the product was separated by column chromatography (eluent: V(petroleum ether):V(ethyl acetate) = 20:1). After concentration, (2Z)-3-amino-3-(4-nitrophenyl)-1-phenylprop-2-en-1-one was obtained as a golden solid, 10 mg, yield 26%. 1 1H NMR (400 MHz, CDCl3): δ = 10.31 (br s, 1H), 8.39–8.30 (m, 2H), 8.04–7.90 (m, 2H), 7.88–7.78 (m, 2H), 7.56–7.42 (m, 3H), 6.16 (s, 1H), 5.35 (s, 1H). 13 13C NMR (101 MHz, CDCl3): δ = 190.7, 159.7, 149.0, 143.8, 139.7, 131.6, 128.5, 127.6, 127.3, 124.3, 93.2.

[0118] Example 17

[0119] (2Z)-3-Amino-3-(2,3-dimethoxyphenyl)-1-phenylprop-2-en-1-one (Compound 1q)

[0120] 2-((1-Methyl-1H-tetrazol-5-yl)sulfinyl)-1-phenylethan-1-one (0.20 mmol, 50 mg) and 2,3-dimethoxybenzaldoxime (0.30 mmol, 54 mg) were added to a 10 mL reaction tube, 0.5 mL of ethanol was added, and the reaction was carried out at 80 °C for 4 hours. After cooling, it was concentrated by evaporation, and separated by column chromatography (eluent: V(petroleum ether):V(ethyl acetate) = 20:1), and after concentration, (2Z)-3-amino-3-(2,3-dimethoxyphenyl)-1-phenylprop-2-en-1-one was obtained as a golden solid, 29 mg, yield 52%. 1 H NMR(400MHz,CDCl3):δ=10.61(br s,1H),8.06–7.88(m,2H),7.49–7.39(m,3H),7.17–7.10(m,2H),7.02(dd,J=6.8,3.0Hz,1H),6.34(s,1H),6.09(s,1H),3.91(s,3H),3.83(s,3H). 13 C NMR(101MHz,CDCl3):δ=190.0,161.3,153.2,147.0,140.5,130.9,130.6,128.3,127.2,124.7,120.9,114.0,92.6,61.4,56.1.

[0121] Example 18

[0122] (2Z)-3-Amino-3-(naphthalen-2-yl)-1-phenylprop-2-en-1-one (Compound 1r)

[0123] 2-((1-Methyl-1H-tetrazol-5-yl)sulfinyl)-1-phenylethan-1-one (0.20 mmol, 50 mg) and 2-naphthaldehyde oxime (0.30 mmol, 51 mg) were added to a 10 mL reaction tube, 0.5 mL of ethanol was added, and the reaction was carried out at 80 °C for 4 hours. After cooling, it was concentrated by evaporation, and separated by column chromatography (eluent: V(petroleum ether):V(ethyl acetate) = 20:1), and after concentration, (2Z)-3-amino-3-(naphthalen-2-yl)-1-phenylprop-2-en-1-one was obtained as a yellow liquid, 24 mg, yield 44%. 11H NMR (400 MHz, CDCl3): δ = 10.50 (br s, 1H), 8.11 (d, J = 1.9 Hz, 1H), 8.02–7.96 (m, 2H), 7.94–7.85 (m, 3H), 7.69 (dd, J = 8.6, 1.9 Hz, 1H), 7.60–7.53 (m, 2H), 7.50–7.41 (m, 3H), 6.27 (s, 1H), 5.66 (br s, 1H). 13 13C NMR (101 MHz, CDCl3): δ = 190.2, 162.9, 140.4, 134.8, 134.4, 133.0, 131.1, 129.0, 128.7, 128.4, 127.8, 127.5, 127.3, 127.0, 126.3, 123.6, 92.3.

[0124] Example 19

[0125] (2Z)-3-Amino-1,4-diphenylbut-2-en-1-one (Compound 1s)

[0126] 2-((1-Methyl-1H-tetrazol-5-yl)sulfinyl)-1-phenylethan-1-one (0.20 mmol, 50 mg) and (1E)-2-phenylacetaldehyde oxime (0.30 mmol, 41 mg) were added to a 10 mL reaction tube, 0.5 mL of ethanol was added, and the reaction was carried out at 80 °C for 4 hours. After cooling, it was evaporated to dryness, and separated by column chromatography (eluent: V(petroleum ether):V(ethyl acetate) = 20:1), and after concentration, (2Z)-3-amino-1,4-diphenylbut-2-en-1-one was obtained as a yellow liquid, 5 mg, yield 11%. 1 1H NMR (400 MHz, CDCl3): δ = 8.10–7.98 (m, 2H), 7.67 (t, J = 7.5 Hz, 1H), 7.54 (t, J = 7.7 Hz, 2H), 7.36–7.30 (m, 2H), 7.27–7.24 (m, 3H), 5.60 (d, J = 5.9 Hz, 1H), 5.50 (br s, 1H), 4.54 (br s, 1H), 3.15 (dd, J = 13.8, 5.2 Hz, 1H), 3.08 (dd, J = 13.8, 8.4 Hz, 1H). 13 13C NMR (101 MHz, CDCl3): δ = 185.9, 135.9, 135.0, 134.8, 129.3, 129.1, 129.0, 128.7, 127.5, 80.5, 43.9, 41.2.

[0127] Example 20

[0128] (2Z)-3-Amino-1-phenyl-3-[4-(triphenylethynyl)phenyl]prop-2-en-1-one (Compound 1t)

[0129] 1,1,2-Triphenyl-2-(4-formylphenyl)ethylene (15 mmol, 5.51 g), potassium carbonate (30 mmol, 4.15 g), and hydroxylamine hydrochloride (30 mmol, 2.08 g) were added to a 100 mL flask. Subsequently, 20 mL of ethanol and 20 mL of water were respectively measured and added to the above system. Stirring was started, and the reaction was carried out at room temperature for 24 hours. After the reaction was completed, the mixture was diluted with ethyl acetate and separated by liquid-liquid extraction. The organic phase was collected, dried over anhydrous sodium sulfate, and then concentrated by rotary evaporation to obtain the crude product. The crude product was recrystallized from an ethyl acetate and petroleum ether system to obtain 1.69 g of pure (E)-[4-(triphenylethynyl)phenyl]methanimine oxime, with a yield of 30%.

[0130] 2-((1-Methyl-1H-tetrazol-5-yl)sulfinyl)-1-phenylethan-1-one (0.20 mmol, 50 mg) and the (E)-[4-(triphenylethynyl)phenyl]methanimine oxime (0.30 mmol, 113 mg) prepared in the above reaction were added to a 10 mL reaction tube. 0.5 mL of ethanol was added, and the reaction was carried out at 80 °C for 4 hours. After cooling, the solvent was removed by rotary evaporation, and the product was separated by column chromatography (eluent: V(petroleum ether):V(ethyl acetate) = 20:1). After concentration, (2Z)-3-amino-1-phenyl-3-[4-(triphenylethynyl)phenyl]prop-2-en-1-one was obtained as a yellow liquid, 31 mg, yield 33%. 1 H NMR (400 MHz, CDCl3): δ = 10.40 (br s, 1H), 7.92 (d, J = 7.3 Hz, 2H), 7.49–7.33 (m, 5H), 7.19–7.08 (m, 11H), 7.08–6.97 (m, 6H), 6.11 (s, 1H), 5.41 (br s, 1H). 13 C NMR (101 MHz, CDCl3): δ = 190.0, 162.4, 146.7, 143.32, 143.29, 143.2, 142.2, 140.4, 139.8, 135.0, 132.0, 131.33, 131.27, 131.0, 128.3, 127.93, 127.87, 127.7, 127.2, 126.9, 126.8, 126.7, 125.7, 91.6.

[0131] The above are only the preferred embodiments of the present invention, and do not impose any form of limitation on the present invention. It should be noted that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and refinements can be made, and these improvements and refinements should also be regarded as the protection scope of the present invention.

Claims

1. A method for preparing β-enaminoketones based on sulfoxides and aldoximes, comprising the following steps: Mixing a compound having the structure shown in Formula 2, an aldoxime, and an organic solvent to carry out a cycloaddition-intramolecular elimination reaction to obtain β-enaminoketones; The β-enaminoketones and aldoximes have the structures shown in Formula 1 and Formula 3 in sequence: In the structures represented by Formula 1 to Formula 3, R 1 , R 2 and R 3 are independently selected from hydrogen, alkyl, alkoxy, cycloalkyl, cycloalkoxy, cycloalkylalkyl, aryl, substituted aryl, aralkyl or heteroaryl, the substituents of the substituted aryl are selected from one or more of hydrogen, alkyl, haloalkyl, alkoxy, aryloxy, fluorine, chlorine, bromine, cyano and nitro, and R 1 and R 3 are not hydrogen.

2. The method according to claim 1, wherein The alkyl group in the straight-chain alkyl or alkoxy group is a straight-chain or branched-chain alkyl group with 1 to 15 carbon atoms; the cycloalkyl or cycloalkoxy group has 3 to 15 carbon atoms; the cycloalkylalkyl group has 4 to 15 carbon atoms; the aryl group in the aryl or substituted aryl group has 6 to 15 carbon atoms; the heteroaryl group has 5 to 15 carbon atoms; the aralkyl group has 7 to 15 carbon atoms.

3. The method according to claim 2, wherein The alkyl group in the straight-chain alkyl or alkoxy group is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, sec-butyl, pentyl, isopentyl, sec-pentyl, neopentyl, hexyl, isohexyl, sec-hexyl, heptyl, isoheptyl, sec-heptyl, octyl, nonyl, decyl, undecyl or dodecyl.

4. The method according to claim 2, characterized in that The cycloalkyl group in the cycloalkyl or cycloalkoxy group is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl; the cycloalkylalkyl group is cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cycloheptylmethyl, cyclooctylmethyl, cyclopropylethyl, cyclobutylethyl, cyclopentylethyl, cyclohexylethyl, cycloheptylethyl, cyclooctylethyl, cyclopropylpropyl, cyclobutylpropyl, cyclopentylpropyl, cyclohexylpropyl, cycloheptylpropyl or cyclooctylpropyl.

5. The method according to claim 2, wherein The aryl group in the aryl, substituted aryl or aralkyl group is phenyl, biphenyl or naphthyl; the heteroaryl group is thiophenyl, furyl or pyridyl.

6. The method according to claim 5, wherein The substituted aryl group is o-methylphenyl, m-methylphenyl, p-methylphenyl, o-methoxyphenyl, m-methoxyphenyl, p-methoxyphenyl, o-fluorophenyl, m-fluorophenyl, p-fluorophenyl, o-chlorophenyl, m-chlorophenyl, p-chlorophenyl, p-bromophenyl, o-nitrophenyl, m-nitrophenyl, p-nitrophenyl, o-cyanophenyl, m-cyanophenyl, p-cyanophenyl, p-trifluoromethylphenyl, 2,3-dimethoxyphenyl or triphenylvinylphenyl.

7. The method according to claim 5, wherein The aralkyl group is benzyl, o-methylbenzyl, m-methylbenzyl, p-methylbenzyl, o-methoxybenzyl, m-methoxybenzyl, p-methoxybenzyl, o-fluorobenzyl, m-fluorobenzyl, p-fluorobenzyl, o-chlorobenzyl, m-chlorobenzyl, p-chlorobenzyl, o-nitrobenzyl, m-nitrobenzyl, p-nitrobenzyl, o-cyanobenzyl, m-cyanobenzyl, p-cyanobenzyl, biphenylmethyl, 1-naphthylmethyl, 2-naphthylmethyl, phenethyl, phenylpropyl, phenylbutyl or phenylpentyl.

8. The method according to any one of claims 1 to 7, characterized in that, The β-enaminoketones have any one of the structures shown in Formula 1a to 1t:

9. The method according to claim 1, wherein The molar ratio of the compound having the structure shown in Formula 2 to the aldoxime is 3:1 to 1:3; the temperature of the cycloaddition-intramolecular elimination reaction is 20 to 150 °C, and the time is 2 to 8 h.

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