Novel method for synthesizing multifunctional aniline derivative through five-component participated benzene cyclization reaction and product thereof

Abstract

The invention belongs to the technical field of organic synthesis, and particularly relates to a novel method for synthesizing a multifunctional aniline derivative through a five-component participated benzene cyclization reaction and a product of the multifunctional aniline derivative. Malononitrile, alkyne aldehyde, a sodium sulfinate derivative, alkali and a solvent are mixed and subjected to a [2 + 2 + 1 + 1] benzene cyclization reaction to prepare the aniline derivative, and the method provided by the invention is simple in steps, easy to operate, wide in reaction substrate application range, good in regioselectivity, high in yield, novel, environment-friendly and suitable for industrial production. The method has a wide application prospect in the aspects of biological science, pharmaceutical industry and material science.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and specifically relates to a new method for synthesizing multifunctional aniline derivatives through a five-component benzene cyclization reaction and a product thereof. Background Art

[0002] Benzene annulation is an unconventional route to assemble aromatic rings via C-C bond formation between two or more acyclic precursors. This reaction mechanism allows the synthesis of aromatic compounds through a specific chemical reaction pathway without the use of benzene or its derivatives. Benzene annulation can avoid time-consuming, reduced reaction steps and waste, and often has excellent regioselectivity, making it an ideal green and sustainable method for benzene ring skeleton editing [1-4].

[0003] In the past few decades, various common benzene annulation reactions have been established to construct substituted aromatics with molecular complexity and diversity, including: [4+2] benzene annulation reaction [5-9] ; [2+2+2] benzene cyclization reaction [10-11] ; [3+3] benzene cyclization reaction [12-14] ; [5+1] benzene cyclization [15-16] ; [3+2+1] benzene cyclization reaction [17-18] .

[0004] However, there are few reports on the ordered assembly of more components, such as the multi-component [2+2+1+1] benzene cyclization reaction. [19-20] .

[0005] Therefore, studying a novel, efficient and compatible [2+2+1+1] reaction is of great significance for expanding the diverse synthesis of aromatics.

[0006] Aromatic amines are organic compounds containing aromatic rings and amino groups. They are widely used in drug synthesis, dye and pigment manufacturing, high-performance polymer production, and as catalysts or ligands in organic synthesis. Their key role in medicine, materials science and industry makes them one of the indispensable basic chemicals in modern chemistry.

[0007] However, there is no prior art report on the preparation of such compounds by novel [2+2+1+1] benzene cyclization reaction.

[0008] The references are as follows:

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[0016] (8)C.-L.Zhang,S.Ye,N-Heter℃yclic Carbene-Catalyzed Construction of1,3,5-Trisubstituted Benzenes from Bromoenals andα-Cyano-β-methylenones.Org.Lett.2016,18,6408-6411.

[0017] (9)D.Wang,J.Lin,Y.Zhu,Y.Huang,De Novo Construction ofSubstitutedTerephthalates via Phosphine Catalyzed Domino BenzannulationReactions.Adv.Synth.Catal.2021,363,1873-1877.

[0018] (10)W.-M.Shu,K.-L.Zheng,J.-R.Ma,A.-X.Wu,Transition-Metal-FreeMulticomponent Benzannulation Reactions forthe Construction ofPolysubstitutedBenzene Derivatives.Org.Lett.2015,17,5216-521.

[0019] (11)K.R.Deaton,M.S.Gin,Regioselective[2+2+2]Cycloaddition of aNickel-Benzyne Complex with 1,3-Diynes.Org.Lett.2003,5,2477-2480.

[0020] (12)Zhou,J.;Shi,X.;Zheng,H.;Chen,G.;Zhang,C.;Liu,X.;Cao,H.Deconstructive Cycloaromatization Strategy toward N,O-Bidentate LigandsfromIndolizines and Cyclopropenones.Org.Lett.2022,24,3238-3243.

[0021] (13)Liu,X.;Zhou,J.;Zheng,H.;Liu,J.;Liu,Z.;Ni,L.;Kong,X.;Zhang,C.;Cao,H.Synthesisand Optical Properties of Polyaryl 2-(Pyridin-2-yl)phenol-BasedFour-Coordinate Organoboron Complexes.Chin.J.Chem.2023,41,924-930.

[0022] (14)Chen,S.Y.;Zeng,Y.F.;Zou,W.X.;Shen,D.T.;Zheng,Y.C.;Song,J.L.;Zhang,S.S.Divergent Synthesis of Tetrasubstituted Phenols via[3+3]Cycloaddition Reaction of VinylSulfoxonnium Ylides withCyclopropenones.Org.Lett.2023,25,4286-4291.

[0023] (15)X.Bi,D.Dong,Q.Liu,W.Pan,L.Zhao,B.Li,[5+1]Annulation:ASyntheticStrategy for Highly Substituted Phenols and Cyclohexenones.J.Am.Chem.S℃.2005,127,4578-4579.

[0024] (16)Z.Fu,M.Wang,Y.Dong,J.Liu,Q.Liu,Direct Synthesis ofHighlySubstituted 2-Cyclohexenones and Sterically Hindered BenzophenonesBased on a[5C+1C]Annulation.J.Org.Chem.2009,74,6105-6110.

[0025] (17)Kim,S.;Chung,Y.K.Rhodium-Catalyzed Carbonylative[3+2+1]Cycloaddition of Alkyne-Tethered Alkylidenecyclopropanes to Phenols inthePresence of Carbon Monoxide.Org.Lett.2014,16,4352-4355.

[0026] (18)Du,T.;Li,S.;He,Y.;Long,H.;Liu,X.;Li,H.-B.;Liu,L.Copper-Catalyzed[3+2+1]Cycloaddition of Alkenes with Benzoquinones and DicarbonylCompoundsvia Tandem Oxidative Dicarbofunctionalization / Cyclization Sequence,Chin.J.Chem.2022,40,1681-1686.

[0027] (19)W.Wei,KKCheung,R.Lin,LCKong,KLChan,HHYSung,IDWilliams,R.Tong,Z.Lin,G.Jia,[2+2+1+1]Cycloaddition for de novo Synthesis ofDenselyFunctionalized Phenols,Angew.Chem.Int.Ed.2023,62,e202307251.

[0028] (20)Y.Ma,T.Xu,F.Xiao,G.Mao,G.-J.Deng,Modular synthesis of unsymmetric2,4-diaryl-substituted pyridines through a four-component cyclizationstrategy under metal-free conditions,Org.Chem.Front.,2023,10,4794-4799. Summary of the invention

[0029] Terms and Claims of the Present Invention:

[0030] Unless otherwise specified, the term "alkyl" as used herein includes branched and straight chain saturated aliphatic hydrocarbon groups having a specified number of carbon atoms, including all isomers. Common abbreviations for alkyl groups, such as methyl, can be represented by "Me" or CH3, ethyl, can be represented by "Et" or CH2CH3, propyl, can be represented by "Pr" or CH2CH2CH3, butyl, can be represented by "Bu" or CH2CH2CH2CH3, etc. For example, "C 1-4 "C1-C4 alkyl" refers to a straight or branched chain alkyl group having a specified number of carbon atoms, including all isomers. 1-4 Alkyl includes n-, iso-, sec- and tert-butyl, n- and iso-propyl, ethyl and methyl. 1-10 "Alkyl" and the like have similar meanings.

[0031] The term "halogen" (or "halo") refers to fluorine, chlorine, bromine, and iodine (alternatively referred to as fluoro (F), chloro (Cl), bromo (Br), and iodo (I)).

[0032] The term "heteroalkyl" refers to an alkyl group (wherein alkyl is as defined herein) wherein one or more carbon atoms are independently replaced by one or more heteroatoms (eg, nitrogen, oxygen, phosphorus and / or sulfur atoms).

[0033] The term "aryl" refers to aromatic mono- and polycyclic carbon ring systems wherein the individual carbon rings in the polycyclic system are fused or linked to each other by single bonds. Typical aryl groups include phenyl, naphthyl and biphenylene.

[0034] The aryl group in the term "substituted aryl" is as defined above. When the substituent of the substituted aryl group is not specified, the substituent may be selected from the following groups, including but not limited to: halogen, C1-C 20 Alkyl, CF3, NH2, N(C1-C6 alkyl)2, NO2, oxo, CN, N3, -OH, -O(C1-C6 alkyl), C3-C 10 Cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, (C0-C6 alkyl)S(O) 0-2 -, Aryl-S(O) 0-2 -, (C0-C6 alkyl)S(O) 0-2 (C0-C6 alkyl)-, (C0-C6 alkyl)C(O)NH-, H2N-C(NH)-, -O(C1-C6 alkyl)CF3, (C0-C6 alkyl)C(O)-, (C0-C6 alkyl)OC(O)-, (C0-C6 alkyl)2NC(O)-(C0-C6 alkyl)O(C1-C6 alkyl)-, (C0-C6 alkyl)C(O) 1-2 (C0-C6 alkyl)-, (C0-C6 alkyl)OC(O)NH-, aryl, aralkyl, heteroaryl, heterocyclylalkyl, halogen-aryl, halogen-aralkyl, halogen-heterocycle, halogen-heterocyclylalkyl, cyano-aryl, cyano-aralkyl, cyano-heterocycle and cyano-heterocyclylalkyl. The term "substituted phenyl" has a similar definition.

[0035] In view of the above problems, the present invention provides a novel method for synthesizing multifunctional aniline derivatives through a five-component benzene cyclization reaction and a product thereof.

[0036] To achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0037] On the one hand, the present invention provides a novel method for synthesizing multifunctional aniline derivatives by a five-component benzene cyclization reaction, wherein malononitrile, acetylaldehyde, a sodium sulfinate derivative, a base and a solvent are mixed to undergo a [2+2+1+1] benzene cyclization reaction to prepare aniline derivatives, and the reaction formula is as follows:

[0038]

[0039] Ar is a substituted or unsubstituted aryl group, and R is selected from an alkyl group, a substituted or unsubstituted aryl group, and an aromatic heterocyclic group.

[0040] In some preferred embodiments, the substituent of the substituted aryl group is selected from alkyl, heteroalkyl, aryl or halogen.

[0041] In some preferred embodiments, the aryl group is a phenyl group.

[0042] In some preferred embodiments, the alkyl group is a C1-C4 alkyl group, preferably a methyl group.

[0043] In some preferred embodiments, the heteroatom of the aromatic heterocyclic group is selected from O, S, and N, and is preferably S.

[0044] In some preferred embodiments, the heteroatom of the heteroalkyl group is selected from O, S, and N, and is preferably O.

[0045] In some preferred embodiments, the halogen is selected from F, Cl, Br and I, preferably Cl.

[0046] In some preferred embodiments, the formula II is selected from the following structures:

[0047]

[0048] Further preferably, the formula II is selected from the following structures:

[0049] More preferably, the formula II is selected from the following structures:

[0050] More preferably, the formula II is

[0051] In some preferred embodiments, the formula III is selected from the following structures:

[0052]

[0053] Further preferably, the formula III is selected from the following structures:

[0054] More preferably, the formula III is selected from the following structures:

[0055] In some preferred embodiments, the base is selected from inorganic bases and / or organic bases.

[0056] In some preferred embodiments, the inorganic base includes but is not limited to at least one of K2CO3, Na2CO3, NaHCO3, Cs2CO3, and Li2CO, preferably K2CO3.

[0057] In some preferred embodiments, the organic base includes but is not limited to triethylamine, pyridine, N,N-dimethylformamide, preferably triethylamine.

[0058] In some preferred embodiments, the solvent is selected from at least one of EA (ethyl acetate), THF (tetrahydrofuran), 1,4-dioxane (1,4-dioxane), and MeCN (acetonitrile), preferably ethyl acetate.

[0059] In some preferred embodiments, the molar ratio of malononitrile, acetylene aldehyde and sodium sulfinate derivative is 2:2:1-2, and examples thereof include 2:2:1, 2:2:1.2, 2:2:1.4, 2:2:1.5, 2:2:1.6, 2:2:1.8, and 2:2:2, but is not limited to the listed values, and other unlisted values ​​within the numerical range are also applicable.

[0060] More preferably, the molar ratio of malononitrile, acetylene aldehyde and sodium sulfinate derivative is 2:2:1.5.

[0061] In some preferred embodiments, the molar ratio of the base to malononitrile is 1:1-3, examples of which include 1:1, 1:1.5, 1:2, 1:2.5, and 1:3, but are not limited to the listed values, and other unlisted values ​​within the numerical range are also applicable.

[0062] More preferably, the molar ratio of the base to malononitrile is 1:1.

[0063] In some preferred embodiments, the ratio of malononitrile to solvent is 0.2-0.4mmol:1mL, examples of which include 0.2mmol:1mL, 0.3mmol:1mL, and 0.4mmol:1mL, but not limited to the listed values, and other unlisted values ​​within the numerical range are also applicable.

[0064] More preferably, the ratio of malononitrile to solvent is 0.2 mmol:1 mL.

[0065] In some preferred embodiments, the temperature of the benzene cyclization reaction is 60-100°C, and examples include 60°C, 70°C, 80°C, 90°C, and 100°C, but are not limited to the listed values. Other values ​​not listed within the numerical range are also applicable. The reaction time is 1-3h, and examples include 1h, 1.5h, 2h, 2.5h, and 3h, but are not limited to the listed values. Other values ​​not listed within the numerical range are also applicable.

[0066] More preferably, the temperature of the benzene cyclization reaction is 80° C. and the reaction time is 2 h.

[0067] The reaction mechanism of the novel method for synthesizing multifunctional aniline derivatives by five-component benzene cyclization provided by the present invention may be: under alkaline conditions, two molecules of malononitrile undergo self-coupling to form intermediate VI, and the two carbon nucleophilic sites in intermediate VI then react with two molecules of acetylene aldehyde to form intermediate VII. After heating, intermediate VII leaves OH - and CN - , forming a conjugated enyne intermediate VIII, which undergoes intramolecular cyclization and is simultaneously attacked by a nucleophilic attack from a sodium benzenesulfinate derivative to form a cyclic intermediate IX, which is then aromatized to obtain the target product, which is represented by formula II. Formula III is The reaction process for example is as follows:

[0068]

[0069] Another aspect of the present invention provides multifunctional aniline derivatives obtained by the novel method.

[0070] Compared with the prior art, the present invention has the following beneficial effects:

[0071] The invention provides a novel method for synthesizing multifunctional aniline derivatives through a benzene cyclization reaction involving five components. The method has simple steps, is easy to operate, has a wide range of application of reaction substrates, has good regional selectivity, has a high yield, is novel, and is environmentally friendly, and has broad application prospects in biological sciences, pharmaceutical industry, and materials science. DETAILED DESCRIPTION

[0072] In order to make the technical means, creative features, purpose and effect of the present invention easy to understand, the present invention is further explained below in conjunction with specific embodiments, but the following embodiments are only preferred embodiments of the present invention, not all. Based on the embodiments in the implementation mode, other embodiments obtained by those skilled in the art without making creative work all belong to the protection scope of the present invention. It is worth noting that the raw materials used in the present invention are all common commercial products, and their sources are not specifically limited. The technology and scientific terms used in the embodiments have the meanings commonly understood by those of ordinary skill in the art to which the present invention belongs.

[0073] Embodiment 1:

[0074] 39.6 mg (0.6 mmol) of malononitrile, 78.0 mg (0.6 mmol) of acetylene aldehyde, 73.8 mg (0.45 mmol) of sodium benzenesulfinate, K2CO3 (82.9 mg, 0.6 mmol) and ethyl acetate (3 mL) as shown in the following formula were added into a sealed reaction tube with a stirring bar, dissolved and stirred at 80°C for 2 h, cooled, spin-dried to remove the solvent, and separated by preparative TLC (thin layer chromatography) to obtain the target product in a yield of 79%.

[0075]

[0076] The 1H-NMR and 13C-NMR spectra of the target product are as follows:

[0077] 1 H NMR (400MHz, DMSO-d6) δ8.29 (s, 1H), 7.73 (d, J = 7.1Hz, 2H), 7.68-

[0078] 7.57(m,5H),7.56-7.47(m,5H),7.40(dd,J=5.1,2.1Hz,3H),7.22(s,2H),6.05(s,1H).

[0079] 13 C NMR (100MHz, DMSO-d6) δ151.8,137.7,137.5,134.4,132.3,132.0,131.8,130.6,129.9,129. 3,129.1,129.02,129.00,128.6,122.0,120.2,115.8,114.9,102.5,98.6,96.6,83.2,70.3.

[0080] HRMS (GC / QTOF) m / z: [M] + Calculate for C 29 H 19 N3O2S,473.1198; found 473.1199.

[0082] Embodiment 2:

[0083] 39.6 mg (0.6 mmol) of malononitrile, 86.4 mg (0.6 mmol) of acetylene aldehyde, 73.8 mg (0.45 mmol) of sodium benzenesulfinate, K2CO3 (82.9 mg, 0.6 mmol) and ethyl acetate (3 mL) as shown in the following formula were added to a reaction tube with a stirring bar, dissolved and stirred at 80°C for 2 h, cooled, spin-dried to remove the solvent, and separated by preparative TLC to obtain the target product with a yield of 72%.

[0084]

[0085] The 1H-NMR and 13C-NMR spectra of the target product are as follows:

[0086] 1H NMR (400MHz, DMSO-d6) δ8.25(s,1H),7.72(d,J=7.2Hz,2H),7.66(t,J=7.5Hz,1H),7.52(dd,J=7.8,2.2Hz ,3H),7.49-7.44(m,3H),7.34(d,J=7.9Hz,2H),7.22-7.18(m,4H),5.99(s,1H),2.39(s,3H),2.28(s,3H).

[0087] 13 C NMR(100MHz,DMSO-d6)δ151.7,140.8,138.6,137.6,134.4,132.4,131.9,129.7,129.7,129.5 ,129.3,128.8,128.5,122.1,117.3,115.9,114.9,103.0,98.4,96.3,82.9,70.1,21.3,20.7.

[0088] HRMS (GC / QTOF) m / z: [M] + Calculate for C 31 H 23 N3O2S,501.1511; found501.1502.

[0089] Embodiment 3:

[0090] 39.6 mg (0.6 mmol) of malononitrile, 96.0 mg (0.6 mmol) of acetylene aldehyde, 73.8 mg (0.45 mmol) of sodium benzenesulfinate, K2CO3 (82.9 mg, 0.6 mmol) and ethyl acetate (3 mL) as shown in the following formula were added into a sealed reaction tube with a stirring bar, dissolved and stirred at 80°C for 2 h, cooled, spin-dried to remove the solvent, and separated by preparative TLC to obtain the target product in a yield of 62%.

[0091]

[0092] The 1H-NMR and 13C-NMR spectra of the target product are as follows:

[0093] 1H NMR (400MHz, CDCl3) δ8.35(s,1H),7.67(s,2H),7.56(t,J=7.5Hz,1H),7.48(d,J=8.8Hz,2H),7.40(dt,J=7.6, 3.4Hz,4H),6.94(d,J=8.8Hz,2H),6.88(d,J=8.8Hz,2H),5.92(s,1H),5.24(s,2H),3.87(s,3H),3.80(s,3H).

[0094] 13 C NMR (100MHz, CDCl3) δ161.5,160.3,150.7,138.0,136.8,134.2,134.0,133.3,131.0,129.1,129 .0,125.0,123.8,115.6,114.8,114.7,114.6,112.8,105.0,99.7,96.7,82.7,55.6,55.5,29.8.

[0095] HRMS(ESI)m / z:[M+Na] + Calculate for C 31 H 23 N3O4NaS,556.1301; found 556.1310.

[0097] Embodiment 4:

[0098] 39.6 mg (0.6 mmol) of malononitrile, 108.0 mg (0.6 mmol) of acetylene aldehyde, 73.8 mg (0.45 mmol) of sodium benzenesulfinate, K2CO3 (82.9 mg, 0.6 mmol) and ethyl acetate (3 mL) as shown in the following formula were added into a sealed reaction tube with a stirring bar, dissolved and stirred at 80°C for 2 h, cooled, spin-dried to remove the solvent, and separated by preparative TLC to obtain the target product in a yield of 68%.

[0099]

[0100] The 1H-NMR and 13C-NMR spectra of the target product are as follows:

[0101] 1 H NMR (400MHz, DMSO-d6) δ8.43(d,J=7.3Hz,1H),8.33(dd,J=6.1,3.4Hz,1H),8.25(s,1H),8.15(dd,J=11.9,8.4Hz,2H),8.10-8.06(m,1H),8.04-

[0102] 7.94(m,3H),7.78-7.74(m,2H),7.73-7.64(m,4H),7.54(t,J=7.4Hz,1H),7.48-7.43(m,1H),7.39-7.29(m,5H),6.93(s,1H).

[0103] 13 C NMR (100MHz, DMSO-d6) δ152.1,138.8,137.6,134.4,133.5,132.8,132.4,132.2,131.18,131.15,129.5,129.3,129.2,128.8,128. 3,127.7,127.3,127.2,127.0,126.1,125.8,125.7,125.2,122.1,121.8,117.6,115.7,115.4,100.4,98.1,96.9,87.9,65.5,39.5.

[0104] HRMS(ESI)m / z:[M+Na] + Calculate for C 37 H 23 N3O2SNa,596.1403; found 596.1405.

[0106] Embodiment 5:

[0107] 39.6 mg (0.6 mmol) of malononitrile, 78.0 mg (0.6 mmol) of acetylene aldehyde, 80.1 mg (0.45 mmol) of sodium benzenesulfinate, K2CO3 (82.9 mg, 0.6 mmol) and ethyl acetate (3 mL) as shown in the following formula were added into a sealed reaction tube with a stirring bar, dissolved and stirred at 80°C for 2 h, cooled, spin-dried to remove the solvent, and separated by preparative TLC to obtain the target product in a yield of 80%.

[0108]

[0109] The 1H-NMR and 13C-NMR spectra of the target product are as follows:

[0110] 1 H NMR (400MHz, CDCl3) δ8.38 (s, 1H), 7.59-7.40 (m, 9H), 7.40-7.33 (m, 3H), 7.21-7.14 (m, 2H), 5.96 (s, 1H), 5.29 (d, J = 2.6Hz, 2H), 2.36 (s, 3H).

[0111] 13 C NMR (100MHz, CDCl3) δ150.8,145.4,137.0,134.9,132.9,132.3,132.2,130.5,129.8,129. 7,129.3,129.0,128.9,125.2,120.9,115.5,114.7,104.0,100.1,97.3,83.3,71.4,21.8.

[0112] HRMS(ESI)m / z:[M+Na] + Calculate for C 30 H 21 N3O2NaS,510.1247; found 510.1250.

[0114] Embodiment 6:

[0115] 39.6 mg (0.6 mmol) of malononitrile, 78.0 mg (0.6 mmol) of acetylene aldehyde, 89.1 mg (0.45 mmol) of sodium benzenesulfinate, K2CO3 (82.9 mg, 0.6 mmol) and ethyl acetate (3 mL) as shown in the following formula were added into a sealed reaction tube with a stirring bar, dissolved and stirred at 80°C for 2 h, cooled, spin-dried to remove the solvent, and separated by preparative TLC to obtain the target product in a yield of 73%.

[0116]

[0117] The 1H-NMR and 13C-NMR spectra of the target product are as follows:

[0118] 1 H NMR (400MHz, CDCl3) δ8.37 (s, 1H), 7.56 (t, J = 8.4Hz, 4H), 7.52-7.41 (m, 5H), 7.40-7.33 (m, 5H), 5.95 (s, 1H), 5.31 (d, J = 8.2Hz, 2H).

[0119] 13 C NMR (100MHz, CDCl3) δ150.9,141.2,136.9,136.4,132.9,132.2,131.9,130.7,130.4,129.7 ,129.55,129.53,129.4,129.0,124.6,120.8,115.4,114.6,104.3,100.3,97.4,83.2,71.6.

[0120] HRMS (GC / QTOF) m / z: [M] + calcdfor C 29 H 18 ClN3O2S,507.9920; found507.9910.

[0121] Embodiment 7:

[0122] 39.6 mg (0.6 mmol) of malononitrile, 78.0 mg (0.6 mmol) of acetylene aldehyde, 76.5 mg (0.45 mmol) of sodium benzenesulfinate, K2CO3 (82.9 mg, 0.6 mmol) and ethyl acetate (3 mL) as shown in the following formula were added to a reaction tube with a stirring bar, dissolved and stirred at 80°C for 2 h, cooled,

[0123] The solvent was removed by spin drying and the target product was separated by preparative TLC with a yield of 49%.

[0124]

[0125] The 1H-NMR and 13C-NMR spectra of the target product are as follows:

[0126] 1 H NMR (400MHz, CDCl3) δ8.36 (s, 1H), 7.65 (dd, J = 5.0, 1.3Hz, 1H), 7.68-7.62 (m, 4H), 7.61 -7.49(m,4H),7.47-7.40(m,3H),7.02(dd,J=4.9,3.8Hz,1H),6.10(s,1H),5.35(s,2H).

[0127] 13 C NMR (100MHz, CDCl3) δ151.0,138.5,137.0,135.7,135.4,133.0,132.3,132.1,130.6,129. 6,129.5,129.4,128.9,128.0,124.9,120.8,115.4,114.7,104.2,100.1,97.3,83.2,72.7.

[0128] HRMS (GC / QTOF) m / z: [M] + Calculate for C 27 H 17 N3O2S2,479.0762; found 479.0765.

[0130] Embodiment 8:

[0131] 39.6 mg (0.6 mmol) of malononitrile, 78.0 mg (0.6 mmol) of acetylene aldehyde, 76.5 mg (0.45 mmol) of sodium benzenesulfinate, K2CO3 (82.9 mg, 0.6 mmol) and ethyl acetate (3 mL) as shown in the following formula were added into a sealed reaction tube with a stirring bar, dissolved and stirred at 80°C for 2 h, cooled, spin-dried to remove the solvent, and separated by preparative TLC to obtain the target product in a yield of 78%.

[0132]

[0133] The 1H-NMR and 13C-NMR spectra of the target product are as follows:

[0134] 1 H NMR(400MHz,DMSO-d6)δ8.31(s,1H),7.76-7.70(m,2H),7.63-7.59(m,2H),7 .57-7.52(m,3H),7.46-7.39(m,3H),7.21(s,2H),6.10(s,1H),3.04(s,3H).

[0135] 13 C NMR(100MHz,DMSO-d6)δ151.8,136.8,132.5,132.3,132.1,130.6,130.0,129 .6,129.1,128.9,122.8,120.5,116.0,115.1,103.1,99.4,96.4,83.8,68.4.

[0136] HRMS(ESI)m / z:[M+Na] + Calculate for C 24 H 17 N3O2NaS,434.0934; found 434.0940.

[0138] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions of the technical solution of the present invention by ordinary technicians in this field do not deviate from the essence and scope of the technical solution of the present invention.

Claims

1. A novel method for synthesizing multifunctional aniline derivatives by a five-component benzene cyclization reaction, characterized in that: Aniline derivatives are prepared by mixing malononitrile, acetylaldehyde, sodium sulfinate derivatives, base and solvent to undergo [2+2+1+1] benzene cyclization reaction, and the reaction formula is as follows: Ar is a substituted or unsubstituted aryl group, and R is selected from an alkyl group, a substituted or unsubstituted aryl group, and an aromatic heterocyclic group.

2. The novel method according to claim 1, wherein the substituent of the substituted aryl group is selected from alkyl, heteroalkyl, aryl or halogen.

3. The novel method according to claim 1 or 2, characterized in that: The formula II is selected from the following structures:

4. The novel method according to claim 3, characterized in that The formula II is selected from the following structures:

5. The novel method according to claim 4, characterized in that: The formula II is selected from the following structures:

6. The novel method according to claim 1 or 2, characterized in that: The formula III is selected from the following structures:

7. The novel method according to claim 6, characterized in that: The formula III is selected from the following structures:

8. The novel method according to any one of claims 1 to 7, characterized in that: The molar ratio of the malononitrile, the acetylene aldehyde and the sodium sulfinate derivative is 2:2:1-2.

9. The novel method according to claim 8, characterized in that The temperature of the benzene cyclization reaction is 60-100° C., and the reaction time is 1-3 hours.

10. The multifunctional aniline derivative obtained by the novel method according to any one of claims 1 to 9.

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