A method for preparing (E)-N N-disubstituted-N′-sulfonylamidinium

Abstract

The application belongs to the technical field of synthesis of sulfonamidines in organic synthesis, and provides a method for preparing (E)-NN-disubstituted-N'-sulfonylamidine derivatives as shown in general formula (I). A series of diversified polysubstituted N-sulfonylamidine derivatives with the structure of formula (I) can be synthesized by the method. The method has the advantages of mild reaction conditions, good functional group compatibility, wide substrate universality and high reaction yield. The application provides a basis for constructing a polysubstituted N-sulfonylamidine small molecule compound library, and lays a material foundation for further exploring the biological activity of polysubstituted N-sulfonylamidine compounds. Meanwhile, the application also provides a new technical means for the rapid synthesis of related active natural products and drug molecules with a polysubstituted N-sulfonylamidine structure skeleton.

Description

Technical Field

[0001] This invention relates to an efficient method for preparing multi-substituted sulfonyl amidine derivatives. More specifically, it relates to a method for preparing (E)-N N-disubstituted-N′-sulfonyl amidine derivatives of formula (I). This invention belongs to the field of sulfonamide synthesis technology in organic synthetic chemistry.

[0002] Background Technology

[0003] (E)-N N-disubstituted-N′-sulfonylamidinium derivatives are a very important class of nitrogen-containing structural skeletons, widely found in many complex active natural products and important drug molecules. [1] Due to their unique chemical and pharmacological properties, sulfonylamidine has been widely used in pharmaceutical and other fields. In addition, sulfonylamidine also plays a crucial role in agricultural chemicals. In particular, the sulfonamide fragment itself is considered a key pharmacophore in many pharmaceutical formulations, and compounds containing sulfonamide structural units often exhibit a variety of biological activities. For example, small-molecule quinoline compounds containing sulfonamide structural fragments have shown significant antitumor activity both in vitro and in vivo, such as good inhibitory activity against human breast cancer cell lines. [2] Furthermore, sulfonylamidinium can also serve as a key synthetic intermediate for the further synthesis of novel and complex compounds. [3] Meanwhile, sulfonylamidinium can also act as a ligand for metal catalysts and is widely used in transition metal-catalyzed chemical reactions. [4] Developing and establishing new methods for synthesizing (E)-N N-disubstituted-N′-sulfonylamidinium derivatives is of great significance for the synthesis of related natural molecules and drug molecules.

[0004] Currently, the preparation of N-sulfonylamidinium mainly relies on the transformation of prefunctional components, and the main synthetic strategies include the condensation between sulfonamides (or sulfonyl azides) and amides. [5] However, these strategies typically require harsh reaction conditions, such as multiple metal catalysts, corrosive and toxic reagents, and most reactions need to be carried out at high temperatures. Therefore, it is crucial to develop concise and novel synthetic methods for N-sulfonylamidines.

[0005] Triazole chemistry has become a hot research area in recent years. Triazoles are widely used in the synthesis of compounds with cyclic or chain-like nitrogen-containing structures. However, research on the synthesis of sulfonylamidines using triazole chemistry has never been reported.

[0006] Based on the above background, this invention develops a method for the selective synthesis of (E)-NN-disubstituted-N′-sulfonylamidinium derivatives using triazoles and substituted enamine ketones as reactants and metal Rh as a catalyst. This invention not only provides a novel method for the synthesis of substituted sulfonylamidinium derivatives but also further expands the chemical reactivity of enamine ketones.

[0007] References

[0008] [1]J.Barker,M.Kilner,Coord.Chem.Rev,1994,133,219.

[0009] [2]H.Turkmen,G.Zengin,B.Buyukkircali,Bioorganic Chemistry2011,39,114.

[0010] [3] RLMackman, BAKatz, JGBreitenbucher, HCHui, E.Verner, C.Luong, L.Liu and PASprengeler, J.Med.Chem, 2001, 44, 3856.

[0011] [4] B. Huang, C. Yang, J. Zhou, W. Xia, Chem. Commun, 2020, 56, 5010.

[0012] [5]W. Yang, D. Huang, X. Zeng, D. Luo, X. Wang and Y. Hu, Chem. Commun, 2018, 54, 8222. Summary of the Invention

[0013] The purpose of this invention is to provide a method for preparing (E)-N N-disubstituted-N′-sulfonylamidinium derivatives.

[0014] To achieve the above objectives, the present invention employs the following technical means:

[0015] Based on the understanding of the chemical reaction properties of (E)-3-(disubstituted amino)-1-substituted-2-enone 1 and 4-phenyl-1-sulfonyl-1H-1,2,3-triazole 2, this invention synthesizes a series of (E)-N N-disubstituted-N′-sulfonylamidine derivatives as shown in formula (I) through extensive screening of reaction conditions such as metal Rh catalysts, reaction solvents, and reaction temperatures.

[0016]

[0017] In Equation (I)1, R 1 The term refers to a straight-chain or branched saturated alkyl group with 1 to 12 carbon atoms, a cyclic alkyl group with 3 to 8 carbon atoms, an epoxypropane group, an epoxybutane group, a 2-thienyl group, a 2-furanyl group, a naphthyl group, a biphenyl group, a pyridyl group, a piperidinyl group, a morpholinyl group, a phenyl group, or a phenyl group with 1 to 2 substituted groups at any position, wherein the substituents on the phenyl group are optionally substituted by the following groups: halogen, phenyl, NO2, methoxy, ethoxy, phenoxy, trifluoromethyl, cyano, hydroxyl, or a straight-chain or branched saturated alkyl group containing 1 to 6 carbon atoms.

[0018] In Equation 1, R 2 The term refers to a straight-chain or branched saturated alkyl group with 1 to 12 carbon atoms, a cyclic alkyl group with 3 to 8 carbon atoms, an epoxypropane group, an epoxybutane group, a 2-thienyl group, a 2-furanyl group, a naphthyl group, a biphenyl group, a pyridyl group, a piperidinyl group, a morpholinyl group, a phenyl group, or a phenyl group with 1 to 2 substituted groups at any position, wherein the substituents on the phenyl group are optionally substituted by the following groups: halogen, phenyl, NO2, methoxy, ethoxy, phenoxy, trifluoromethyl, cyano, hydroxyl, or a straight-chain or branched saturated alkyl group containing 1 to 6 carbon atoms.

[0019] In Equation 1, R 4 The term refers to a straight-chain or branched saturated alkyl group with 1 to 12 carbon atoms, a cyclic alkyl group with 3 to 8 carbon atoms, an epoxypropane group, an epoxybutane group, a 2-thienyl group, a 2-furanyl group, a naphthyl group, a biphenyl group, a pyridyl group, a piperidinyl group, a morpholinyl group, a phenyl group, or a phenyl group with 1 to 2 substituted groups at any position, wherein the substituents on the phenyl group are optionally substituted by the following groups: halogen, phenyl, NO2, methoxy, ethoxy, phenoxy, trifluoromethyl, cyano, hydroxyl, or a straight-chain or branched saturated alkyl group containing 1 to 6 carbon atoms.

[0020] In Equation (I)2, R 3 The term refers to a straight-chain or branched saturated alkyl group with 1 to 6 carbon atoms, a cyclic alkyl group with 3 to 8 carbon atoms, an epoxypropane group, an epoxybutane group, a 2-thienyl group, a 2-furanyl group, a naphthyl group, a biphenyl group, a phenyl group, or a phenyl group with 1 to 2 substituted groups at any position, wherein the substituents on the phenyl group are optionally substituted with the following groups: halogen, phenyl, NO2, methoxy, ethoxy, phenoxy, trifluoromethyl, cyano, hydroxyl, or a straight-chain or branched saturated alkyl group containing 1 to 6 carbon atoms.

[0021] In Equation 2, R 5The term represents 2-thienyl, 2-furanyl, naphthyl, biphenyl, pyridyl, piperidinyl, morpholinyl, phenyl, or phenyl with 1 to 2 substituted positions, wherein the substituents on the phenyl are optionally substituted by the following groups: halogen, phenyl, NO2, methoxy, ethoxy, phenoxy, trifluoromethyl, cyano, hydroxyl, or a straight-chain or branched saturated alkyl group containing 1 to 6 carbon atoms.

[0022] In equation (I), R 1 The term refers to a straight-chain or branched saturated alkyl group with 1 to 12 carbon atoms, a cyclic alkyl group with 3 to 8 carbon atoms, an epoxypropane group, an epoxybutane group, a 2-thienyl group, a 2-furanyl group, a naphthyl group, a biphenyl group, a pyridyl group, a piperidinyl group, a morpholinyl group, a phenyl group, or a phenyl group with 1 to 2 substituted groups at any position, wherein the substituents on the phenyl group are optionally substituted by the following groups: halogen, phenyl, NO2, methoxy, ethoxy, phenoxy, trifluoromethyl, cyano, hydroxyl, or a straight-chain or branched saturated alkyl group containing 1 to 6 carbon atoms.

[0023] In equation (I), R 2 The term refers to a straight-chain or branched saturated alkyl group with 1 to 12 carbon atoms, a cyclic alkyl group with 3 to 8 carbon atoms, an epoxypropane group, an epoxybutane group, a 2-thienyl group, a 2-furanyl group, a naphthyl group, a biphenyl group, a pyridyl group, a piperidinyl group, a morpholinyl group, a phenyl group, or a phenyl group with 1 to 2 substituted groups at any position, wherein the substituents on the phenyl group are optionally substituted by the following groups: halogen, phenyl, NO2, methoxy, ethoxy, phenoxy, trifluoromethyl, cyano, hydroxyl, or a straight-chain or branched saturated alkyl group containing 1 to 6 carbon atoms.

[0024] In formula (I) R 3 The term refers to a straight-chain or branched saturated alkyl group with 1 to 6 carbon atoms, a cyclic alkyl group with 3 to 8 carbon atoms, an epoxypropane group, an epoxybutane group, a 2-thienyl group, a 2-furanyl group, a naphthyl group, a biphenyl group, a phenyl group, or a phenyl group with 1 to 2 substituted groups at any position, wherein the substituents on the phenyl group are optionally substituted with the following groups: halogen, phenyl, NO2, methoxy, ethoxy, phenoxy, trifluoromethyl, cyano, hydroxyl, or a straight-chain or branched saturated alkyl group containing 1 to 6 carbon atoms.

[0025] This invention first synthesizes simple substrates and explores the feasibility of the reaction through extensive condition screening. Using phenyl-substituted (E)-3-(dimethylamino)-1-phenylprop-2-en-1-one enamine 1a and phenyl-substituted triazole 4-phenyl-1-toluenesulfonyl-1H-1,2,3-triazole 2a as model substrates, 3a was synthesized for condition screening. Based on this, substrate tolerance was investigated, and a series of (E)-N,N-dimethyl-N'-toluenesulfonylimine derivatives with the general formula (I) were synthesized.

[0026]

[0027] The general structural formula of (E)-N N-disubstituted-N′-sulfonylamidinium derivatives is shown in formula (I):

[0028]

[0029] In formula (I) R 1 The term (I) refers to a straight-chain or branched saturated alkyl group with 1 to 12 carbon atoms, a cyclic alkyl group with 3 to 8 carbon atoms, glycidyl oxide, glycidyl oxide, 2-thienyl, 2-furanyl, naphthyl, biphenyl, pyridyl, piperidinyl, morpholinyl, phenyl, or a phenyl group with 1 to 2 substituted groups at any position, wherein the substituents on the phenyl group are optionally substituted with the following groups: halogen, phenyl, NO2, methoxy, ethoxy, phenoxy, trifluoromethyl, cyano, hydroxyl, or a straight-chain or branched saturated alkyl group containing 1 to 6 carbon atoms. Specifically, R in formula (I) 1 When R is a straight-chain or branched saturated alkyl group containing 1 to 12 carbon atoms, it may be methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, undecyl, or dodecyl; 1 When the alkyl group has 3 to 8 carbon atoms, it may be optionally cyclopropane, cyclobutanealkyl, cyclopentane, cyclohexyl, 4-methylcyclohexyl, 1,3-dicyclohexylpropane, octahydro-1H-indole, cycloheptane, or cyclooctyl; R in formula (I) 1 When the phenyl group is halogen-substituted, the halogen is selected from F, Cl, Br, and I.

[0030] In formula (I) R 2 The term (I) refers to a straight-chain or branched saturated alkyl group with 1 to 12 carbon atoms, a cyclic alkyl group with 3 to 8 carbon atoms, glycidyl oxide, glycidyl oxide, 2-thienyl, 2-furanyl, naphthyl, biphenyl, pyridyl, piperidinyl, morpholinyl, phenyl, or a phenyl group with 1 to 2 substituted groups at any position, wherein the substituents on the phenyl group are optionally substituted with the following groups: halogen, phenyl, NO2, methoxy, ethoxy, phenoxy, trifluoromethyl, cyano, hydroxyl, or a straight-chain or branched saturated alkyl group containing 1 to 6 carbon atoms. Specifically, R in formula (I) 2 When R is a straight-chain or branched saturated alkyl group containing 1 to 12 carbon atoms, it may be methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, undecyl, or dodecyl; 2When the alkyl group has 3 to 8 carbon atoms, it may be optionally cyclopropane, cyclobutanealkyl, cyclopentane, cyclohexyl, 4-methylcyclohexyl, 1,3-dicyclohexylpropane, octahydro-1H-indole, cycloheptane, or cyclooctyl; R in formula (I) 2 When the phenyl group is halogen-substituted, the halogen is selected from F, Cl, Br, and I.

[0031] In formula (I) R 3 The term (I) represents a straight-chain or branched saturated alkyl group with 1 to 6 carbon atoms, a cyclic alkyl group with 3 to 8 carbon atoms, an epoxypropane group, an epoxybutane group, a 2-thienyl group, a 2-furanyl group, a naphthyl group, a biphenyl group, a phenyl group, or a phenyl group with 1 to 2 substituted groups at any position, wherein the substituents on the phenyl group are optionally substituted with the following groups: halogen, phenyl, NO2, methoxy, ethoxy, phenoxy, trifluoromethyl, cyano, hydroxyl, or a straight-chain or branched saturated alkyl group containing 1 to 6 carbon atoms. Specifically, R in formula (I) 3 When R is a straight-chain or branched saturated alkyl group containing 1 to 6 carbon atoms, it may be methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, n-pentyl, or n-hexyl; 3 When the alkyl group is a cyclic alkyl group with 3 to 8 carbon atoms, it may be optionally a cyclopropane group, a cyclobutane group, a cyclopentane group, a cyclohexyl group, a cycloheptane group, or a cyclooctane group; R in formula (I) 3 When the phenyl group is halogen-substituted, the halogen is selected from F, Cl, Br, and I.

[0032] The method includes the following steps:

[0033] Using Rh2(esp)2 as a metal catalyst and DCE as a reaction solvent, (E)-3-(dimethylamino)-1-phenylprop-2-en-1-one enamino ketone derivative 1 and 4-phenyl-1-toluenesulfonyl-1H-1,2,3-triazole derivative 2 were mixed at 100 °C and heated for 30 minutes to synthesize the (E)-N N-disubstituted-N′-sulfonylamidinium derivative shown in formula (I):

[0034]

[0035] Preferably, R in Formula 1 1The following groups are listed: methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, undecyl, dodecyl, propylene oxide, butyl oxide, 2-thienyl, 2-furanyl, naphthyl, biphenyl, pyridyl, piperidinyl, morpholinyl, cyclopropane group, cyclobutane alkyl, cyclopentyl, cyclohexyl, 4-methylcyclohexyl, 1,3-dicyclohexylpropane, octahydro-1H-indole, cycloheptyl, cyclooctyl, phenyl, 4-methylphenyl, 4-ethylphenyl, 4-propylphenyl, 4-butylphenyl, 4-pentylphenyl, 4-isopropylphenyl, 4-isobutylphenyl, 4-methoxyphenyl, 4-ethoxyphenyl. 4-Nitrophenyl, 4-Cyanophenyl, 4-Hydroxyphenyl, 4-Trifluoromethylphenyl, 4-Fluorophenyl, 4-Chlorophenyl, 4-Bromophenyl, 4-Iodophenyl, 2-Methylphenyl, 2-Ethylphenyl, 2-Methoxyphenyl, 2-Nitrophenyl, 2-Cyanophenyl, 2-Hydroxyphenyl, 2-Trifluoromethylphenyl, 2-Fluorophenyl, 2-Chlorophenyl, 2-Bromophenyl, 2-Iodophenyl, 3-Methylphenyl, 3-Ethylphenyl, 3-Propylphenyl, 3-Methoxyphenyl, 3-Ethoxyphenyl, 3-Nitrophenyl, 3-Cyanophenyl, 3-Hydroxyphenyl, 3-Trifluoromethylphenyl, 3-Fluorophenyl, 3-Chlorophenyl, 3-Bromophenyl, 3-Iodophenyl.

[0036] Preferably, R in Formula 1 2 The following groups are listed: methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, undecyl, dodecyl, propylene oxide, butyl oxide, 2-thienyl, 2-furanyl, naphthyl, biphenyl, pyridyl, piperidinyl, morpholinyl, cyclopropane group, cyclobutane alkyl, cyclopentyl, cyclohexyl, 4-methylcyclohexyl, 1,3-dicyclohexylpropane, octahydro-1H-indole, cycloheptyl, cyclooctyl, phenyl, 4-methylphenyl, 4-ethylphenyl, 4-propylphenyl, 4-butylphenyl, 4-pentylphenyl, 4-isopropylphenyl, 4-isobutylphenyl, 4-methoxyphenyl, 4-ethoxyphenyl. 4-Nitrophenyl, 4-Cyanophenyl, 4-Hydroxyphenyl, 4-Trifluoromethylphenyl, 4-Fluorophenyl, 4-Chlorophenyl, 4-Bromophenyl, 4-Iodophenyl, 2-Methylphenyl, 2-Ethylphenyl, 2-Methoxyphenyl, 2-Nitrophenyl, 2-Cyanophenyl, 2-Hydroxyphenyl, 2-Trifluoromethylphenyl, 2-Fluorophenyl, 2-Chlorophenyl, 2-Bromophenyl, 2-Iodophenyl, 3-Methylphenyl, 3-Ethylphenyl, 3-Propylphenyl, 3-Methoxyphenyl, 3-Ethoxyphenyl, 3-Nitrophenyl, 3-Cyanophenyl, 3-Hydroxyphenyl, 3-Trifluoromethylphenyl, 3-Fluorophenyl, 3-Chlorophenyl, 3-Bromophenyl, 3-Iodophenyl.

[0037] Preferably, R in Formula 1 4The following groups are listed: methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, undecyl, dodecyl, cyclopropane, cyclobutane, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, propylene oxide, butyl oxide, 2-thienyl, 2-furanyl, naphthyl, biphenyl, pyridyl, piperidinyl, morpholinyl, phenyl, 4-methylphenyl, 4-ethylphenyl, 4-propylphenyl, 4-butylphenyl, 4-pentylphenyl, 4-isopropylphenyl, 4-isobutylphenyl, 4-methoxyphenyl, 4-ethoxyphenyl, 4-nitrophenyl, 4-cyanophenyl. 4-hydroxyphenyl, 4-trifluoromethylphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 2-methylphenyl, 2-ethylphenyl, 2-methoxyphenyl, 2-nitrophenyl, 2-cyanophenyl, 2-hydroxyphenyl, 2-trifluoromethylphenyl, 2-fluorophenyl, 2-chlorophenyl, 2-bromophenyl, 2-iodophenyl, 3-methylphenyl, 3-ethylphenyl, 3-propylphenyl, 3-methoxyphenyl, 3-ethoxyphenyl, 3-nitrophenyl, 3-cyanophenyl, 3-hydroxyphenyl, 3-trifluoromethylphenyl, 3-fluorophenyl, 3-chlorophenyl, 3-bromophenyl, 3-iodophenyl.

[0038] Preferably, R in Equation 2 3 The following groups are used: methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, n-hexyl, cyclopropane group, cyclobutane alkyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 2-thienyl, 2-furanyl, naphthyl, biphenyl, pyridyl, piperidinyl, morpholinyl, phenyl, 4-methylphenyl, 4-ethylphenyl, 4-propylphenyl, 4-butylphenyl, 4-pentylphenyl, 4-isopropylphenyl, 4-isobutylphenyl, 4-methoxyphenyl, 4-ethoxyphenyl, 4-nitrophenyl, 4-cyanophenyl, 4-hydroxyphenyl, 4-trifluoromethylphenyl, 4 -Fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 2-methylphenyl, 2-ethylphenyl, 2-methoxyphenyl, 2-nitrophenyl, 2-cyanophenyl, 2-hydroxyphenyl, 2-trifluoromethylphenyl, 2-fluorophenyl, 2-chlorophenyl, 2-bromophenyl, 2-iodophenyl, 3-methylphenyl, 3-ethylphenyl, 3-propylphenyl, 3-methoxyphenyl, 3-ethoxyphenyl, 3-nitrophenyl, 3-cyanophenyl, 3-hydroxyphenyl, 3-trifluoromethylphenyl, 3-fluorophenyl, 3-chlorophenyl, 3-bromophenyl, 3-iodophenyl.

[0039] Preferably, R in Equation 2 5The following are listed: methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, n-hexyl, 2-thienyl, 2-furanyl, naphthyl, biphenyl, pyridyl, piperidinyl, morpholinyl, phenyl, 4-methylphenyl, 4-ethylphenyl, 4-propylphenyl, 4-butylphenyl, 4-pentylphenyl, 4-isopropylphenyl, 4-isobutylphenyl, 4-methoxyphenyl, 4-ethoxyphenyl, 4-nitrophenyl, 4-cyanophenyl, 4-hydroxyphenyl, 4-trifluoromethylphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl 4-Iodophenyl, 2-Methylphenyl, 2-Ethylphenyl, 2-Methoxyphenyl, 2-Nitrophenyl, 2-Cyanophenyl, 2-Hydroxyphenyl, 2-Trifluoromethylphenyl, 2-Fluorophenyl, 2-Chlorophenyl, 2-Bromophenyl, 2-Iodophenyl, 3-Methylphenyl, 3-Ethylphenyl, 3-Propylphenyl, 3-Methoxyphenyl, 3-Ethoxyphenyl, 3-Nitrophenyl, 3-Cyanophenyl, 3-Hydroxyphenyl, 3-Trifluoromethylphenyl, 3-Fluorophenyl, 3-Chlorophenyl, 3-Bromophenyl, 3-Iodophenyl.

[0040] Preferably, in formula (I), R 1 The following groups are listed: methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, undecyl, dodecyl, propylene oxide, butyl oxide, 2-thienyl, 2-furanyl, naphthyl, biphenyl, pyridyl, piperidinyl, morpholinyl, cyclopropane group, cyclobutane alkyl, cyclopentyl, cyclohexyl, 4-methylcyclohexyl, 1,3-dicyclohexylpropane, octahydro-1H-indole, cycloheptyl, cyclooctyl, phenyl, 4-methylphenyl, 4-ethylphenyl, 4-propylphenyl, 4-butylphenyl, 4-pentylphenyl, 4-isopropylphenyl, 4-isobutylphenyl, 4-methoxyphenyl, 4-ethoxyphenyl. 4-Nitrophenyl, 4-Cyanophenyl, 4-Hydroxyphenyl, 4-Trifluoromethylphenyl, 4-Fluorophenyl, 4-Chlorophenyl, 4-Bromophenyl, 4-Iodophenyl, 2-Methylphenyl, 2-Ethylphenyl, 2-Methoxyphenyl, 2-Nitrophenyl, 2-Cyanophenyl, 2-Hydroxyphenyl, 2-Trifluoromethylphenyl, 2-Fluorophenyl, 2-Chlorophenyl, 2-Bromophenyl, 2-Iodophenyl, 3-Methylphenyl, 3-Ethylphenyl, 3-Propylphenyl, 3-Methoxyphenyl, 3-Ethoxyphenyl, 3-Nitrophenyl, 3-Cyanophenyl, 3-Hydroxyphenyl, 3-Trifluoromethylphenyl, 3-Fluorophenyl, 3-Chlorophenyl, 3-Bromophenyl, 3-Iodophenyl.

[0041] Preferably, in formula (I), R 2The following groups are listed: methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, undecyl, dodecyl, propylene oxide, butyl oxide, 2-thienyl, 2-furanyl, naphthyl, biphenyl, pyridyl, piperidinyl, morpholinyl, cyclopropane group, cyclobutane alkyl, cyclopentyl, cyclohexyl, 4-methylcyclohexyl, 1,3-dicyclohexylpropane, octahydro-1H-indole, cycloheptyl, cyclooctyl, phenyl, 4-methylphenyl, 4-ethylphenyl, 4-propylphenyl, 4-butylphenyl, 4-pentylphenyl, 4-isopropylphenyl, 4-isobutylphenyl, 4-methoxyphenyl, 4-ethoxyphenyl. 4-Nitrophenyl, 4-Cyanophenyl, 4-Hydroxyphenyl, 4-Trifluoromethylphenyl, 4-Fluorophenyl, 4-Chlorophenyl, 4-Bromophenyl, 4-Iodophenyl, 2-Methylphenyl, 2-Ethylphenyl, 2-Methoxyphenyl, 2-Nitrophenyl, 2-Cyanophenyl, 2-Hydroxyphenyl, 2-Trifluoromethylphenyl, 2-Fluorophenyl, 2-Chlorophenyl, 2-Bromophenyl, 2-Iodophenyl, 3-Methylphenyl, 3-Ethylphenyl, 3-Propylphenyl, 3-Methoxyphenyl, 3-Ethoxyphenyl, 3-Nitrophenyl, 3-Cyanophenyl, 3-Hydroxyphenyl, 3-Trifluoromethylphenyl, 3-Fluorophenyl, 3-Chlorophenyl, 3-Bromophenyl, 3-Iodophenyl.

[0042] Preferably, in formula (I), R 3 The following groups are used: methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, n-hexyl, cyclopropane group, cyclobutane alkyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 2-thienyl, 2-furanyl, naphthyl, biphenyl, pyridyl, piperidinyl, morpholinyl, phenyl, 4-methylphenyl, 4-ethylphenyl, 4-propylphenyl, 4-butylphenyl, 4-pentylphenyl, 4-isopropylphenyl, 4-isobutylphenyl, 4-methoxyphenyl, 4-ethoxyphenyl, 4-nitrophenyl, 4-cyanophenyl, 4-hydroxyphenyl, 4-trifluoromethylphenyl, 4 -Fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 2-methylphenyl, 2-ethylphenyl, 2-methoxyphenyl, 2-nitrophenyl, 2-cyanophenyl, 2-hydroxyphenyl, 2-trifluoromethylphenyl, 2-fluorophenyl, 2-chlorophenyl, 2-bromophenyl, 2-iodophenyl, 3-methylphenyl, 3-ethylphenyl, 3-propylphenyl, 3-methoxyphenyl, 3-ethoxyphenyl, 3-nitrophenyl, 3-cyanophenyl, 3-hydroxyphenyl, 3-trifluoromethylphenyl, 3-fluorophenyl, 3-chlorophenyl, 3-bromophenyl, 3-iodophenyl.

[0043] Preferably, the amount of (E)-3-(dimethylamino)-1-phenylpropyl-2-enone 1 is equal to the molar amount of 4-phenyl-1-toluenesulfonyl-1H-1,2,3-triazole derivative 2, the amount of metal Rh2(esp)2 as catalyst is 2% of the molar amount of enone 1 derivative, the reaction temperature is from room temperature to 100°C, and the reaction time is 30 minutes.

[0044] Preferably, the method further includes monitoring the reaction process using thin-layer chromatography. After the reaction is completed, the reaction solvent DCE is removed by vacuum distillation. The residue is separated by silica gel column chromatography, with petroleum ether-ethyl acetate as the eluent. The volume ratio of petroleum ether to ethyl acetate is 3:1. A solid or oily product is obtained, which is the purified derivative of formula (I) (E)-N N-disubstituted-N′-sulfonylamidine.

[0045] The preparation process of this invention can be represented by the following reaction formula:

[0046]

[0047] Raw materials 1 and 2 in the preparation method of this invention can be purchased directly or prepared by existing methods. For example, they can be prepared by the following methods:

[0048] 1) Mix 4 different substituted acetylaceton derivatives and equimolar amounts of disubstituted amines in THF solvent and stir at room temperature for 12 hours to obtain (E)-3-(dimethylamino)-1-phenylpropyl-2-enone derivative 1.

[0049]

[0050] 2) Different substituted phenylacetylene derivatives 6 and equimolar amounts of substituted sulfonyl azide 7 were stirred in toluene, and catalyst CuTc (20%) was added. The mixture was stirred at room temperature for 12 hours to obtain 4-phenyl-1-sulfonyl-1H-1,2,3-triazole derivative 2.

[0051]

[0052] Compared with the prior art, the beneficial effects of the present invention are:

[0053] This invention provides a method for the efficient synthesis of (E)-N N-disubstituted-N′-sulfonylamidine derivatives using enaminophenones and triazoles. This method enables the synthesis of a diverse range of polysubstituted (E)-N N-disubstituted-N′-sulfonylamidine derivatives as shown in Formula (I). Compared to conventional methods for synthesizing polysubstituted sulfonylamidines, this novel method offers significant advantages: 1) the substrates triazole and enaminophenone can be prepared from simple and inexpensive precursors; 2) this method synthesizes various (E)-N N-disubstituted-N′-sulfonylamidines and their derivatives with different substitution types in excellent yields, demonstrating good substrate versatility. This invention provides a method for constructing libraries of sulfonylamidine small molecule compounds and lays a solid material foundation for subsequent in-depth biological activity studies. Furthermore, this invention also provides a new technical means for the synthesis of active natural products and small molecule drug molecules with sulfonylamidine structural skeletons. Detailed Implementation

[0054] To further illustrate the present invention, a series of embodiments are given below. These embodiments are purely illustrative and are only used to specifically describe the present invention, and should not be construed as limiting the present invention.

[0055] The specific implementation method is as follows:

[0056] Example 1: Preparation of (E)-N,N-dimethyl-N'-tosylformimidamide

[0057]

[0058] Weigh (E)-3-(dimethylamino)-1-phenyl-2-enone 1a (35 mg) and 4-phenyl-1-p-toluenesulfonyl-1H-1,2,3-triazole 2a (60 mg), add them to 1.5 mL of solvent DCE and stir. Add 3.1 mg of bis[(α,α,α′,α′-tetramethyl-1,3-phenylenediol)rhodium] catalyst. React at 100 °C for 30 min, remove the organic solvent under reduced pressure and perform column chromatography to give a white solid (E)-N,N-dimethyl-N'-toluenesulfonylmethyleneimine amide 3a (36.5 mg, 83%). 1 H NMR (CDCl3, 500MHz): δ = 8.11 (s, 1H), 7.75 (d, J = 8.0, 2H), 7.24 (d, J = 8.0, 2H), 3.10 (s, 3H), 2.99 (s, 3H), 2.38 (s, 3H) ppm; 13C NMR (125MHz, CDCl3): δ = 159.2, 142.5, 139.7, 129.4, 126.6, 41.5, 35.6, 21.6ppm; HRMS (ESI): m / z calcd for C 10 H 15 N₂O₂S[M+H] + 227.0848; found 227.0849.

[0059] Example 2: Preparation of (E)-N-methyl-N-phenyl-N'-tosylformimidamide

[0060]

[0061] Weigh (E)-3-(methyl(phenyl)amino)-1-phenylprop-2-en-1-one 1b (47 mg) and 4-phenyl-1-p-toluenesulfonyl-1H-1,2,3-triazole 2a (60 mg), add them to 1.5 mL of solvent DCE and stir. Add 3.1 mg of bis[(α,α,α′,α′-tetramethyl-1,3-phenylenediol)rhodium] catalyst. React at 100 °C for 30 min, remove the organic solvent under reduced pressure and perform column chromatography to give a white solid (E)-N-methyl-N-phenyl-N'-toluenesulfonylmethyleneimine amide 3b (24 mg, 41%). 1 H NMR (CDCl3, 500MHz): δ = 8.51 (s, 1H), 7.77-7.76 (m, 2H), 7.40-7.35 (m, 2H), 7.28-7.22 (m, 3H), 7.14-7.13 (m, 2H), 3.38 (s, 3H), 2.36 (s, 3H) ppm; 13 C NMR (125MHz, CDCl3): δ = 158.5, 143.3, 143.0, 139.0, 130.0, 129.5, 127.4, 126.8, 122.1, 36.1, 21.6ppm; HRMS (ESI): m / z calcdfor C 15 H 17 N₂O₂S[M+H] + 289.0702; found 289.0702.

[0062] Example 3: Preparation of (E)-4-methyl-N-(pyrrolidin-1-ylmethylene)benzenesulfonamide

[0063]

[0064] Weigh (E)-1-phenyl-3-(pyrrolidone-1-yl)prop-2-en-1-one 1c (40 mg) and 4-phenyl-1-p-toluenesulfonyl-1H-1,2,3-triazole 2a (60 mg), add them to 1.5 mL of solvent DCE and stir. Add 3.1 mg of bis[(α,α,α′,α′-tetramethyl-1,3-phenylenediol)rhodium] catalyst. React at 100 °C for 30 min, remove the organic solvent under reduced pressure and perform column chromatography to obtain a white solid ((E)-4-methyl-N-(pyrrolidone-1-ylmethylene)benzenesulfonamide 3c (40 mg). 1 H NMR (CDCl3, 500MHz): δ = 8.30 (s, 1H), 7.70 (d, J = 8.4Hz, 2H), 7.24 (d, J = 8.0Hz, 2H), 3.57 (t, J = 6.4Hz, 2H), 3.45 (t, J = 6.4Hz, 2H), 2.38 (s, 3H), 1.95 1.92(m,4H)ppm; 13C NMR (100MHz, CDCl3): δ = 155.9, 142.4, 139.8, 129.4, 126.6, 50.1, 46.5, 25.1, 24.5, 21.6ppm; HRMS (ESI): m / z calcd for C12H17N2O2S[M+H]+253.1000; found 253.1005.

[0065] Example 4: Preparation of 4-methyl-N-((E)-((3aR,7aS)-octahydro-2H-isoindol-2-yl)methylene)benzenesulfonamide

[0066]

[0067] Weigh out 51 mg of (E)-3-((3aR,7aS)-octahydro-2H-isoindol-2-yl)-1-phenylprop-2-en-1-one 1d and 60 mg of 4-phenyl-1-p-toluenesulfonyl-1H-1,2,3-triazole 2a, add them to 1.5 mL of solvent DCE and stir. Add 3.1 mg of bis[(α,α,α′,α′-tetramethyl-1,3-phenylenediol)rhodium] catalyst. React at 100 °C for 30 min, remove the organic solvent under reduced pressure and perform column chromatography to give a white solid (4-methyl-N-((E)-((3aR,7aS)-octahydro-2H-isoindol-2-yl)methylene)benzenesulfonamide 3d (40 mg, 88%). 1 H NMR (CDCl3, 500MHz): δ = 8.28 (s, 1H), 7.76 (d, J = 8.0Hz, 2H), 7.23 (d, J = 7.6Hz, 2H), 3.57 (dd, J1 = 10.8Hz, J2 = 6.8Hz, 1H), 3.45 -3.38(m,2H),2.31(dd,J1=12.0Hz,J2=7.2Hz,1H),2.37(s,3H),2.30-2.18(m,2H),1.62-1.54(m,2H),1.53-1.29(m,6H)ppm; 13 C NMR (100MHz, CDCl3): δ = 156.6, 142.3, 139.8, 129.3, 126.6, 54.1, 50.1, 36.8, 36.1, 25.5, 25.4, 22.8, 22.0, 21.5ppm; HRMS (ESI): m / z calcd for C 16 H 23 N₂O₂S[M+H] + 307.1469; found 307.1475.

[0068] Example 5: Preparation of (E)-4-methyl-N-(piperidin-1-ylmethylene)benzenesulfonamide

[0069]

[0070] Weigh ((E)-1-phenyl-3-(piperidin-1-yl)prop-2-en-1-one 1e (43 mg) and 4-phenyl-1-p-toluenesulfonyl-1H-1,2,3-triazole 2a (60 mg), add to 1.5 mL of solvent DCE and stir. Add 3.1 mg of bis[(α,α,α′,α′-tetramethyl-1,3-phenylenediol)rhodium] catalyst. React at 100 °C for 30 min, remove the organic solvent under reduced pressure and perform column chromatography to give a white solid ((E)-4-methyl-N-(piperidin-1-ylmethylene)benzenesulfonamide 3e (44 mg, 82%). 1 H NMR (CDCl3, 500MHz): δ = 8.10 (s, 1H), 7.75 (d, J = 8.0Hz, 2H), 7.23 (d, J = 8.0Hz, 2H) ,3.57(t,J=5.0Hz,2H),3.39(t,J=4.5Hz,2H),2.38(s,3H),1.68-1.52(m,6H)ppm; 13 C NMR (125MHz, CDCl3): δ = 157.4, 142.4, 139.9, 129.4, 126.5, 52.0, 44.7, 26.5, 24.9, 24.0, 21.5ppm; HRMS (ESI): m / z calcd for C 13 H 19 N₂O₂S[M+H] + 267.1429; found 267.1432.

[0071] Example 6: Preparation of (E)-4-methyl-N-((4-methylpiperidin-1-yl)methylene)benzenesulfonamide

[0072]

[0073] Weigh (E)-3-(4-methylpiperidin-1-yl)-1-phenylprop-2-en-1-one 1f (46 mg) and 4-phenyl-1-p-toluenesulfonyl-1H-1,2,3-triazole 2a (60 mg), add them to 1.5 mL of solvent DCE and stir. Add 3.1 mg of bis[(α,α,α′,α′-tetramethyl-1,3-phenylenediol)rhodium] catalyst. React at 100 °C for 30 min, remove the organic solvent under reduced pressure and perform column chromatography to give a white solid (E)-4-methyl-N-((4-methylpiperidin-1-yl)methylene)benzenesulfonamide 3f (52 mg, 93%). 1HNMR (CDCl3, 500MHz): δ = 8.10 (s, 1H), 7.74 (d, J = 8.0Hz, 2H), 7.23 (d, J = 8.0Hz, 2H), 4.40-4.35 (m, 1H), 3.58-3.52 (m, 1H), 3.24 (td, J1 = 1 2.4Hz,J2=3.2Hz,1H),2.76(td,J1=12.8Hz,J2=3.2Hz,1H),2.37(s,3H),1.77-1.60(m,3H),1.23-1.06(m,2H),0.94(d,J=6.4Hz,3H)ppm; 13 C NMR (100MHz, CDCl3): δ = 157.3, 142.4, 139.8, 129.3, 126.5, 51.2, 44.0, 34.5, 33.0, 30.7, 21.5ppm; HRMS (ESI): m / z calcd for C 14 H 21 N₂O₂S[M+H] + 281.1312; found 281.1318.

[0074] Example 7: Preparation of N,N'-((1E,1'E)-(propane-1,3-diylbis(piperidine-4,1-diyl))bis(methane ylylidene))bis(4-methylbenzenesulfonamide)

[0075]

[0076] Weigh 1 g (94 mg) of (2E1,3-propanedi(4,1-piperidinidyl)bis(1-phenyl-2-propen-1-one) and 2a (60 mg) of 4-phenyl-1-p-toluenesulfonyl-1H-1,2,3-triazole 2a) into 1.5 mL of solvent DCE and stir. Add 3.1 mg of bis[(α,α,α′,α′-tetramethyl-1,3-phenylenediol)rhodium] catalyst. React at 100 °C for 30 min, remove the organic solvent under reduced pressure and perform column chromatography to give 3 g (96 mg, 84%) of white solid N,N'-((1E,1'E)-(propane-1,3-diylbis(piperidin-4,1-diyl))bis(methylene))bis(4-methylbenzenesulfonamide). 1H NMR (CDCl3, 500MHz): δ = 8.10 (s, 2H), 7.74 (d, J = 8.0Hz, 4H), 7.24 (d, J = 8.0Hz, 4H), 4.43-4.38 (m, 2H), 3.59-3.55 (m, 2H), 3.23 (td, J1 = 1 2.8Hz,J2=2.8Hz,2H),2.74(td,J1=12.8Hz,J2=2.8Hz,2H),2.38(s,6H),1.80-1.68(m,4H),1.52-1.46(m,2H),1.29-1.04(m,10H)ppm; 13 C NMR (100MHz, CDCl3): δ = 157.3, 142.5, 139.7, 129.4, 126.6, 51.3, 44.0, 36.2, 35.7, 32.7, 31.2, 23.6, 21.6ppm; HRMS (ESI): m / zcalcd for C 29 H 41 N4O4S2[M+H] + 573.2556; found 573.2564.

[0077] Example 8: Preparation of (E)-NN,N-bisdodecyl-N'-tosylformimidamide

[0078]

[0079] Weigh (E)-3-(bis(dodecylamino)-1-phenylprop-2-en-1-one) 1h (96 mg) and 4-phenyl-1-p-toluenesulfonyl-1H-1,2,3-triazole 2a (60 mg), add them to 1.5 mL of solvent DCE and stir. Add 3.1 mg of bis[(α,α,α′,α′-tetramethyl-1,3-phenylenediol)rhodium] catalyst. React at 100 °C for 30 min, remove the organic solvent under reduced pressure and perform column chromatography to give a white solid (E)-NN,N-bisdodecyl-N'-toluenesulfonylmethyleneimine amide 3h (45 mg, 42%). 1 H NMR (CDCl3, 500MHz): δ = 8.12 (s, 1H), 7.74 (d, J = 8.0Hz, 2H), 7.24 (d, J = 8.0Hz, 2H), 3.38 (t, J = 8.0Hz,2H),3.26(t,J=8.0Hz,2H),2.39(s,3H),1.26-1.20(m,36H),0.88(t,J=7.2Hz,6H)ppm; 13C NMR (100MHz, CDCl3): δ=158.9,142.3,140.0,129.4,126.5,52.7,46.3,32.1,29.8,29.7,29. 7,29.6,29.6,29.5,29.4,29.3,28.8,26.9,26.8,26.6,22.8,21.6,14.3ppm; HRMS(ESI):m / z calcd for C 32 H 59 N₂O₂S[M+H] + 535.4282; found 535.4292.

[0080] Example 9: Preparation of (E)-4-methyl-N-(morpholinomethylene)benzenesulfonamide

[0081]

[0082] Weigh ((E)-3-morpholino-1-phenyl-2-propen-1-one 1i (44 mg)) and 4-phenyl-1-p-toluenesulfonyl-1H-1,2,3-triazole 2a (60 mg), add to 1.5 mL of solvent DCE and stir. Add 3.1 mg of bis[(α,α,α′,α′-tetramethyl-1,3-phenylenediol)rhodium] catalyst. React at 100 °C for 30 min, remove the organic solvent under reduced pressure and perform column chromatography to obtain a white solid (E)-4-methyl-N-(morpholinomethyl)benzenesulfonamide 3i (39 mg, 72%). 1 H NMR (CDCl3, 500MHz): δ = 8.20 (s, 1H), 7.76 (d, J = 8.5Hz, 2H), 7.26 (d, J = 7.5Hz, 2H), 3 .73(t,J=4.5Hz,2H),3.67(t,J=4.5Hz,4H),3.48(t,J=4.5Hz,2H),2.40(s,3H)ppm; 13 C NMR (125MHz, CDCl3): δ = 157.3, 142.4, 139.8, 129.3, 126.5, 51.2, 44.0, 34.5, 33.0, 30.7, 21.5ppm; HRMS (ESI): m / zcalcd for C 12 H 17 N₂O₃S[M+H] + 269.0949; found 269.0954.

[0083] Example 10: Preparation of (E)-N,N-dimethyl-N'-(phenylsulfonyl)formimidamide

[0084]

[0085] Weigh (E)-3-(dimethylamino)-1-phenyl-2-enone 1a (35 mg) and 4-phenyl-1-(benzenesulfonyl)-1H-1,2,3-triazole 2b (57 mg), add them to 1.5 mL of solvent DCE and stir. Add 3.1 mg of bis[(α,α,α′,α′-tetramethyl-1,3-phenylenediol)rhodium] catalyst. React at 100 °C for 30 min, remove the organic solvent under reduced pressure and perform column chromatography to give a white solid (E)-N N-dimethyl-N'-(benzenesulfonyl)methyleneimine amide 3j (33 mg, 78%). 1 H NMR (CDCl3, 500MHz): δ = 88.13 (s, 1H), 7.87 (d, J = 7.5Hz, 2H), 7.51-7.43 (m, 3H), 3.11 (s, 3H), 3.00 (s, 3H) ppm; 13 CNMR (125MHz, CDCl3): δ = 159.3, 142.5, 131.9, 128.8, 126.5, 41.6, 35.6ppm; HRMS (ESI): m / zcalcd for C9H 13 N₂O₂S[M+H] + 213.0687; found 213.0692.

Claims

1. A method for preparing as shown in general formula (I) E Methods for derivatives of )-N N-disubstituted-N′-sulfonylamidinium: (I) in, In formula (I) R 1 The term refers to a straight-chain or branched saturated alkyl group with 1 to 12 carbon atoms, a cyclic alkyl group with 3 to 8 carbon atoms, an epoxypropane group, an epoxybutane group, a 2-thienyl group, a 2-furanyl group, a naphthyl group, a biphenyl group, a pyridyl group, a piperidinyl group, a morpholinyl group, a phenyl group, or a phenyl group with 1 to 2 substituted groups at any position, wherein the substituents on the phenyl group are optionally substituted by the following groups: halogen, phenyl, NO2, methoxy, ethoxy, phenoxy, trifluoromethyl, cyano, hydroxyl, or a straight-chain or branched saturated alkyl group containing 1 to 6 carbon atoms; In formula (I) R 2 The term refers to a straight-chain or branched saturated alkyl group with 1 to 12 carbon atoms, a cyclic alkyl group with 3 to 8 carbon atoms, an epoxypropane group, an epoxybutane group, a 2-thienyl group, a 2-furanyl group, a naphthyl group, a biphenyl group, a pyridyl group, a piperidinyl group, a morpholinyl group, a phenyl group, or a phenyl group with 1 to 2 substituted groups at any position, wherein the substituents on the phenyl group are optionally substituted by the following groups: halogen, phenyl, NO2, methoxy, ethoxy, phenoxy, trifluoromethyl, cyano, hydroxyl, or a straight-chain or branched saturated alkyl group containing 1 to 6 carbon atoms; In formula (I) R 3 The term refers to a straight-chain or branched saturated alkyl group with 1 to 6 carbon atoms, a cyclic alkyl group with 3 to 8 carbon atoms, a propylene oxide group, a butyl oxide group, a 2-thienyl group, a 2-furanyl group, a naphthyl group, a biphenyl group, a phenyl group, or a phenyl group with 1 to 2 substituted groups at any position, wherein the substituents on the phenyl group are optionally substituted by the following groups: halogen, phenyl, NO2, methoxy, ethoxy, phenoxy, trifluoromethyl, cyano, hydroxyl, or a straight-chain or branched saturated alkyl group containing 1 to 6 carbon atoms. The method includes the following steps: Under the conditions of using divalent metal Rh2(esp)2 as a catalyst, with an amount of 2.0 mol% (stoichiometric value) of ketone 1 and DCE as the reaction solvent, ( E )-3-(dimethylamino)-1-phenylpropyl-2-enone derivative 1 and 1-methanesulfonyl-4-phenyl-1H-1,2,3-triazole 1-methanesulfonyl-4-phenyl-1H-1,2,3-triazole derivative 2 were reacted at 100 °C for 30 minutes to synthesize the product shown in formula (I). E )-N N-dimethyl-N′-methanesulfonylimide; ； 12(I) In Equation 1, R 4 The term refers to a straight-chain or branched saturated alkyl group with 1 to 12 carbon atoms, a cyclic alkyl group with 3 to 8 carbon atoms, an epoxypropane group, an epoxybutane group, a 2-thienyl group, a 2-furanyl group, a naphthyl group, a biphenyl group, a pyridyl group, a piperidinyl group, a morpholinyl group, a phenyl group, or a phenyl group with 1 to 2 substituted groups at any position, wherein the substituents on the phenyl group are optionally substituted by the following groups: halogen, phenyl, NO2, methoxy, ethoxy, phenoxy, trifluoromethyl, cyano, hydroxyl, or a straight-chain or branched saturated alkyl group containing 1 to 6 carbon atoms; In Equation 2, R 5 The term represents 2-thienyl, 2-furanyl, naphthyl, biphenyl, pyridyl, piperidinyl, morpholinyl, phenyl, or phenyl with 1 to 2 substituted positions, wherein the substituents on the phenyl are optionally substituted by the following groups: halogen, phenyl, NO2, methoxy, ethoxy, phenoxy, trifluoromethyl, cyano, hydroxyl, or a straight-chain or branched saturated alkyl group containing 1 to 6 carbon atoms.

2. The method as described in claim 1, characterized in that, The R mentioned 1 When R is a straight-chain or branched saturated alkyl group containing 1 to 12 carbon atoms, it may be selected from methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, undecyl, or dodecyl; 1 When it is a cyclic alkyl group with 3 to 8 carbon atoms, it may be optionally cyclopropane, cyclobutanealkyl, cyclopentane, cyclohexyl, 4-methylcyclohexyl, 1,3-dicyclohexylpropane, octahydro-1H-indole, cycloheptane, or cyclooctane.

3. The method as described in claim 1, characterized in that, The R mentioned 2 When R is a straight-chain or branched saturated alkyl group containing 1 to 12 carbon atoms, it may be selected from methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, undecyl, or dodecyl; 1 When it is a cyclic alkyl group with 3 to 8 carbon atoms, it may be optionally cyclopropane, cyclobutanealkyl, cyclopentane, cyclohexyl, 4-methylcyclohexyl, 1,3-dicyclohexylpropane, octahydro-1H-indole, cycloheptane, or cyclooctane.

4. The method as described in claim 1, characterized in that, The R mentioned 3 When the alkyl group is a straight-chain or branched saturated alkyl group containing 1 to 6 carbon atoms, it may be optionally methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, n-pentyl, or n-hexyl; the R... 3 When it is a cyclic alkyl group with 3 to 8 carbon atoms, it may be optionally a cyclopropane group, a cyclobutane group, a cyclopentane group, a cyclohexyl group, a cycloheptane group, or a cyclooctane group.

5. The method as described in claim 1, characterized in that, The R mentioned 4 When R is a straight-chain or branched saturated alkyl group containing 1 to 12 carbon atoms, it may be selected from methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, undecyl, or dodecyl; 4 When it is a cyclic alkyl group with 3 to 8 carbon atoms, it may be optionally a cyclopropane group, a cyclobutane group, a cyclopentane group, a cyclohexyl group, a cycloheptane group, or a cyclooctane group.

6. The method as described in claim 1, characterized in that, The R mentioned 5 When it is a straight-chain or branched saturated alkyl group with 1 to 6 carbon atoms, it may be methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, n-pentyl, or n-hexyl.

7. The method as described in claim 1, characterized in that, The halogens mentioned are selected from F, Cl, Br, and I.

8. The method as described in claim 1, characterized in that, ( E The amount of 1-3-(dimethylamino)-1-phenylpropyl-2-enone was equimolar to the amount of 2-phenyl-1-toluenesulfonyl-1H-1,2,3-triazole derivative, and the amount of metal Rh2(esp)2 catalyst was 2.0 mol% of the stoichiometry of 1-enone. The reaction temperature was 100 °C and the reaction time was 30 minutes.

9. The method as described in claim 1, characterized in that, The method further includes monitoring the reaction progress using thin-layer chromatography, removing the solvent DCE by direct vacuum distillation after the reaction is complete, separating the residue by silica gel column chromatography, using petroleum ether-ethyl acetate as the eluent, wherein the volume ratio of petroleum ether to ethyl acetate is 3:1, to obtain a solid or oily product, which is the purified product represented by formula (I). E )-N N-disubstituted-N′-sulfonylamidinium derivatives.

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