CN109678788B - 1, 2-diaryl indole, derivative and synthetic method thereof - Google Patents

1, 2-diaryl indole, derivative and synthetic method thereof Download PDF

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CN109678788B
CN109678788B CN201910078044.9A CN201910078044A CN109678788B CN 109678788 B CN109678788 B CN 109678788B CN 201910078044 A CN201910078044 A CN 201910078044A CN 109678788 B CN109678788 B CN 109678788B
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CN109678788A (en
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邓国军
李�诚
谢艳军
肖福红
黄华文
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Xiangtan University
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Abstract

The application relates to 1, 2-diaryl indole, derivatives and a synthesis method thereof, and the technical scheme is that under the catalysis of secondary amine, an iodine reagent and a sulfoxide or sulfone reagent are used as additives, and in an organic solvent in an oxygen atmosphere, transition metal is not required to be added, so that the 1, 2-diaryl indole and the derivatives are generated. Compared with the prior art, the invention has the following advantages: 1) the required reagent has stable property, is convenient to store, is cheap and easy to obtain, and is beneficial to reducing the production cost; 2) the synthesis is carried out by a one-pot method, the economic advantages of the steps are very obvious, and the time and the labor are saved; 3) the regioselectivity is excellent, a product with a complex and changeable structure is prepared, and the generation of isomers which are difficult to separate is avoided; 4) transition metal is not needed, so that the pollution of the transition metal to products is eliminated; 5) the reaction takes oxygen as an oxidant and water as the most main byproduct, and is environment-friendly; 6) the whole reaction system is simple, reaction equipment is less, and the experimental operation is simple and convenient.

Description

1, 2-diaryl indole, derivative and synthetic method thereof
Technical Field
The invention relates to 1, 2-diaryl indole, derivatives and a synthesis method thereof, belonging to the field of organic synthesis.
Background
1, 2-diaryl indoles are an important subclass of indole compounds, and many functional materials and biologically active molecules comprise a 1, 2-diaryl indole skeleton. The synthesis methods of 1, 2-diaryl indole compounds so far have the following disadvantages: (I) the needed highly functionalized substrate has the disadvantages of troublesome synthesis, active property, inconvenient storage and limited source; (II) multiple steps are needed, the economical efficiency of the steps is poor, unnecessary waste of manpower and material resources is caused, and the operability is poor; (III) when each aromatic ring of the target product has different groups, the regioselectivity is difficult to control, and isomers which cannot be separated are often generated; (IV) the pollution of the residual transition metal to the product limits the application of the product in the field of drug synthesis, in particular to the synthesis of drug molecules applied to human bodies. Therefore, the 1, 2-diaryl indole compound with a complex and variable synthetic structure has a great promotion effect on the work in the fields of materials, biology and medicine. Meanwhile, it is urgent to develop a method for synthesizing 1, 2-diarylindole compounds by using simple, stable, cheap and easily available starting materials and a regioselective one-pot method under the condition of no transition metal.
Disclosure of Invention
The invention aims to provide 1, 2-diaryl indole and derivatives thereof, which have stable structure and excellent properties and can be used as synthetic building blocks of a plurality of functional materials or synthetic precursors of bioactive molecules.
The invention also provides a synthetic method of the 1, 2-diaryl indole and the derivatives thereof.
The invention provides a 1, 2-diaryl indole compound and a derivative thereof, which are characterized in that the general formula is I-a or I-b:
Figure BSA0000178383840000011
R1selected from: c1-C10OfChain or branched hydrocarbon radicals, ester radicals, substituted or unsubstituted C6-C10One of aryl groups;
R2selected from: one of a hydrogen atom, a halogen atom, and an alkoxy group;
R3selected from: hydrogen atom, halogen atom, trifluoromethoxy group, trifluoromethyl group, nitro group, ester group, alkylsulfonyl group, cyano group, substituted or unsubstituted C6-C10Aryl radical, C1-C10Straight or branched chain hydrocarbon group, hydroxyl group, alkoxy group, substituted or unsubstituted C6-C10One of aryloxy and piperidinyl;
R4selected from: hydrogen atom, halogen atom, C1-C10Linear or branched alkyl, alkoxy, substituted or unsubstituted C6-C10One of aryl and nitro;
Ar1selected from: c6-C10One of aryl groups;
Ar2selected from: c6-C10One of aryl groups.
The invention also provides a method for synthesizing the 1, 2-diaryl indole and the derivatives thereof, which comprises the following steps: heating and stirring a cyclic ketone compound, an aromatic amine compound, an alpha-hydroxy aryl ethanone compound, a secondary amine, an iodine reagent and a sulfoxide or sulfone reagent in an organic solvent under the oxygen atmosphere, and separating and purifying to obtain the product 1, 2-diaryl indole and the derivative thereof.
Preferably, the method of the invention is characterized in that:
the secondary amine is selected from: one or more of N-methylisopropylamine, N-methylbenzylamine, N-methylaniline, N-methylcyclohexylamine, phthalimide, succinimide, cyclohexylimine, tetrahydropyrrole, tetrahydroisoquinoline, indoline, morpholine, thiomorpholine, piperazine, N-methylpiperazine, N-methyl-2-methylpiperazine, piperidine, 4-methylpiperidine, 3, 5-dimethylpiperidine and 3-methylpiperidine;
the iodine reagent is selected from: sodium periodate (NaIO)4) Potassium iodide (KI), ammonium iodide (NH)4I)、Sodium iodide (NaI), Hydrogen Iodide (HI), iodobenzene (PhI), iodobenzene Diacetate (DAIB), and elemental iodine (I)2) And N-iodosuccinimide (NIS);
the sulfoxide or sulfone reagent is selected from: one or more of dimethyl sulfoxide (DMSO), diphenyl sulfoxide, sulfolane, dimethyl sulfone, diphenyl sulfone and phenyl benzyl sulfone;
the organic solvent is selected from: o-xylene (o-xylene), p-xylene (p-xylene), m-xylene (m-xylene), trifluorotoluene (PhCF)3) Toluene (PhCH)3) Chlorobenzene (PhCl), 1, 2-Dichloroethane (DCE), cyclohexane and n-octane.
The molar ratio of the cyclic ketone compound, the aromatic amine compound, the alpha-hydroxy aryl ethanone compound, the secondary amine, the iodine reagent and the sulfoxide (or sulfone) reagent is 1-3: 1-2: 0.1-1: 1-4, the reaction temperature is 100-160 ℃, and the reaction time is 4-24 h.
Preferably, in the method of the present invention, the cyclic ketone compound is selected from the group consisting of cyclohexanone compounds and β -tetralone compounds, and the general formula thereof is II-a or II-b:
Figure BSA0000178383840000021
R1selected from: c1-C10Straight or branched chain hydrocarbon group, ester group, substituted or unsubstituted C6-C10One of aryl groups;
R2selected from: one of a hydrogen atom, a halogen atom, and an alkoxy group;
preferably, in the method of the present invention, the cyclic ketone compound is selected from one of 4-methylcyclohexanone, 4-ethylcyclohexanone, 4-propylcyclohexanone, 4-isopropylcyclohexanone, 4-tert-butylcyclohexanone, 4-tert-amylcyclohexanone, 4-n-amylcyclohexanone, methyl 4-cyclohexanecarboxylate, ethyl 4-cyclohexanecarboxylate, 4-phenylcyclohexanone, 4- (4-hydroxyphenyl) cyclohexanone, 3-methylcyclohexanone, β -tetralone, 6-bromo- β -tetralone, and 7-methoxy- β -tetralone.
Preferably, in the method of the present invention, the aromatic amine compound has the formula III:
Figure BSA0000178383840000022
R3selected from: hydrogen atom, halogen atom, trifluoromethoxy group, trifluoromethyl group, nitro group, ester group, alkylsulfonyl group, cyano group, substituted or unsubstituted C6-C10Aryl radical, C1-C10Straight or branched chain hydrocarbon group, hydroxyl group, alkoxy group, substituted or unsubstituted C6-C10One of aryloxy and piperidinyl;
Ar1selected from: c6-C10One of aryl groups.
Preferably, in the method of the present invention, the aromatic amine compound is selected from: aniline, 2-fluoroaniline, 2-methylaniline, 2-phenylaniline, 3-fluoroaniline, 3-chloroaniline, 3-bromoaniline, 3-trifluoromethoxy aniline, 3-nitroaniline, methyl 3-aminobenzoate, 3-cyanoaniline, 3-methylaniline, 4-fluoroaniline, 4-chloroaniline, 4-bromoaniline, 4-iodoaniline, 4-trifluoromethoxy aniline, 4-trifluoromethylaniline, methyl 4-aminobenzoate, 4-methylsulfonylaniline, 4-nitroaniline, 4-cyanoaniline, 4-phenylaniline, 4-methylaniline, 4-tert-butylaniline, 4-phenoxyaniline, 4-methoxyaniline, 4-hydroxyaniline, 2-phenylaniline, 3-fluoroaniline, 3-chloroaniline, 3-bromoaniline, 4-trifluoromethylaniline, 4-methylsulfanylaniline, 4-nitroaniline, 4, 4-piperidyl aniline and 4-nitro-1-aniline.
Preferably, in the method of the present invention, the α -hydroxyaryl ethanones have the general formula IV:
Figure BSA0000178383840000031
R4selected from: hydrogen atom, halogen atom, C1-C10Linear or branched alkyl, alkoxy, substituted or unsubstituted C6-C10One of aryl and nitro;
Ar2selected from: c6-C10One of aryl groups.
Preferably, in the method of the present invention, the α -hydroxyaryl ethanones are selected from: one of alpha-hydroxyacetophenone, alpha-hydroxy-4-methylacetophenone, alpha-hydroxy-4-methoxyacetophenone, alpha-hydroxy-4-phenylacetophenone, alpha-hydroxy-4-fluoroacetophenone, alpha-hydroxy-3-chloroacetophenone, alpha-hydroxy-3-bromoacetophenone, alpha-hydroxy-3-nitroacetophenone and alpha-hydroxy-2-naphthylacetophenone.
The invention relates to a technical scheme for converting cyclic ketone compounds, aromatic amine compounds and alpha-hydroxy aryl ethanone compounds into 1, 2-diaryl indole and derivatives under the promotion of secondary amine, iodine reagent and sulfoxide or sulfone reagent and in an organic solvent in an oxygen atmosphere without adding transition metal for the first time.
The application also provides an application of the 1, 2-diaryl indole compound and the derivative thereof in the aspect of medicine,
the structural formula of the 1, 2-diaryl indole compound and the derivative thereof is as follows:
Figure BSA0000178383840000032
the use thereof for the preparation of inhibitors of beta-amyloid secretion by hydrolysis;
the structural formula of the 1, 2-diaryl indole compound and the derivative thereof is as follows:
Figure BSA0000178383840000033
when the PASK is hydrolyzed, the application of the PASK activity inhibitor is obtained.
Compared with the prior art, the invention has the following advantages:
(I) the required reagent has stable property, is convenient to store, is cheap and easy to obtain, and is beneficial to reducing the production cost;
(II) one-pot synthesis is adopted, so that the economic advantages of the steps are very obvious, and unnecessary waste of manpower and material resources is reduced;
(III) the regioselectivity is excellent, a product with a complex and changeable structure is prepared, and the generation of isomers which are difficult to separate is avoided;
(IV) transition metal is not needed, thus fundamentally eliminating the pollution of the transition metal to the product;
(V) oxygen is used as a green oxidant in the reaction, so that the method is environment-friendly;
(VI) the whole reaction system is simple, reaction equipment is less, and experimental operation is simple and convenient, so that the method is favorable for popularization and application;
(VII) is particularly suitable for the preparation of functional materials, biologically active molecules and drug molecules.
The present invention will be described in further detail with reference to the accompanying drawings and examples.
Drawings
In order to demonstrate the products of the invention, the invention provides nuclear magnetic hydrogen and carbon spectra of some of the examples.
FIG. 1a is a nuclear magnetic hydrogen spectrum of the product of example 5; FIG. 1b is the NMR spectrum of the product of example 5.
FIG. 2a is a nuclear magnetic hydrogen spectrum of the product of example 7; FIG. 2b is the NMR spectrum of the product of example 7.
FIG. 3a is a nuclear magnetic hydrogen spectrum of the product of example 15; FIG. 3b is the NMR spectrum of the product of example 15.
FIG. 4a is a nuclear magnetic hydrogen spectrum of the product of example 24; FIG. 4b is a nuclear magnetic carbon spectrum of the product of example 24.
FIG. 5a is a nuclear magnetic hydrogen spectrum of the product of example 34; FIG. 5b is a nuclear magnetic carbon spectrum of the product of example 34.
FIG. 6a is a nuclear magnetic hydrogen spectrum of the product of example 44; FIG. 6b is a nuclear magnetic carbon spectrum of the product of example 44.
FIG. 7a is a nuclear magnetic hydrogen spectrum of the product of example 45; FIG. 7b is a nuclear magnetic carbon spectrum of the product of example 45.
FIG. 8a is a nuclear magnetic hydrogen spectrum of the product of example 46; FIG. 8b is a nuclear magnetic carbon spectrum of the product of example 46.
FIG. 9 is a general reaction formula of a method for synthesizing the 1, 2-diarylindole compound and the derivatives thereof according to the present invention.
Detailed Description
The invention provides a 1, 2-diaryl indole compound and a derivative thereof, wherein the general formula of the compound is I-a or I-b:
Figure BSA0000178383840000041
R1selected from: c1-C10Straight or branched chain hydrocarbon group, ester group, substituted or unsubstituted C6-C10One of aryl groups;
R2selected from: one of a hydrogen atom, a halogen atom, and an alkoxy group;
R3selected from: hydrogen atom, halogen atom, trifluoromethoxy group, trifluoromethyl group, nitro group, ester group, alkylsulfonyl group, cyano group, substituted or unsubstituted C6-C10Aryl radical, C1-C10Straight or branched chain hydrocarbon group, hydroxyl group, alkoxy group, substituted or unsubstituted C6-C10One of aryloxy and piperidinyl;
R4selected from: hydrogen atom, halogen atom, C1-C10Linear or branched alkyl, alkoxy, substituted or unsubstituted C6-C10One of aryl and nitro;
Ar1selected from: c6-C10One of aryl groups;
Ar2selected from: c6-C10One of aryl groups.
The invention provides a method for synthesizing 1, 2-diaryl indole and derivatives thereof, which comprises the following steps: heating and stirring a cyclic ketone compound, an aromatic amine compound, an alpha-hydroxy aryl ethanone compound, a secondary amine, an iodine reagent and a sulfoxide or sulfone reagent in an organic solvent under the oxygen atmosphere, and separating and purifying to obtain a product.
In order to improve the comprehensive performance of the invention and realize the optimization of structure and effect, the invention has the further measures that:
the secondary amine is selected from: one or more of N-methylisopropylamine, N-methylbenzylamine, N-methylaniline, N-methylcyclohexylamine, phthalimide, succinimide, cyclohexylimine, tetrahydropyrrole, tetrahydroisoquinoline, indoline, morpholine, thiomorpholine, piperazine, N-methylpiperazine, N-methyl-2-methylpiperazine, piperidine, 4-methylpiperidine, 3, 5-dimethylpiperidine and 3-methylpiperidine;
the iodine reagent is selected from: sodium periodate (NaIO)4) Potassium iodide (KI), ammonium iodide (NH)4I) Sodium iodide (NaI), Hydrogen Iodide (HI), iodobenzene (PhI), iodobenzene Diacetate (DAIB), elemental iodine (I)2) And N-iodosuccinimide (NIS);
the sulfoxide or sulfone reagent is selected from: one or more of dimethyl sulfoxide (DMSO), diphenyl sulfoxide, sulfolane, dimethyl sulfone, diphenyl sulfone and phenyl benzyl sulfone;
the organic solvent is selected from: o-xylene (o-xylene), p-xylene (p-xylene), m-xylene (m-xylene), trifluorotoluene (PhCF)3) Toluene (PhCH)3) Chlorobenzene (PhCl), 1, 2-Dichloroethane (DCE), cyclohexane and n-octane.
The molar ratio of the cyclic ketone compound, the aromatic amine compound, the alpha-hydroxy aryl ethanone compound, the secondary amine, the iodine reagent and the sulfoxide (or sulfone) reagent is 1-3: 1-2: 0.1-1: 1-4, the reaction temperature is 100-160 ℃, and the reaction time is 4-24 h.
Preferably, in the method of the present invention, the cyclic ketone compound is selected from the group consisting of cyclohexanone compounds and β -tetralone compounds, and the general formula thereof is II-a or II-b:
Figure BSA0000178383840000051
R1selected from: c1-C10Straight or branched chain hydrocarbon group, ester group, substituted or unsubstituted C6-C10One of aryl groups;
R2selected from: one of a hydrogen atom, a halogen atom, and an alkoxy group;
preferably, in the method of the present invention, the cyclic ketone compound is selected from one of 4-methylcyclohexanone, 4-ethylcyclohexanone, 4-propylcyclohexanone, 4-isopropylcyclohexanone, 4-tert-butylcyclohexanone, 4-tert-amylcyclohexanone, 4-n-amylcyclohexanone, methyl 4-cyclohexanecarboxylate, ethyl 4-cyclohexanecarboxylate, 4-phenylcyclohexanone, 4- (4-hydroxyphenyl) cyclohexanone, 3-methylcyclohexanone, β -tetralone, 6-bromo- β -tetralone, and 7-methoxy- β -tetralone.
Preferably, in the method of the present invention, the aromatic amine compound has the formula III:
Figure BSA0000178383840000052
R3selected from: hydrogen atom, halogen atom, trifluoromethoxy group, trifluoromethyl group, nitro group, ester group, alkylsulfonyl group, cyano group, substituted or unsubstituted C6-C10Aryl radical, C1-C10Straight or branched chain hydrocarbon group, hydroxyl group, alkoxy group, substituted or unsubstituted C6-C10One of aryloxy and piperidinyl;
Ar1selected from: c6-C10One of aryl groups.
Preferably, in the method of the present invention, the aromatic amine compound is further selected from: aniline, 2-fluoroaniline, 2-methylaniline, 2-phenylaniline, 3-fluoroaniline, 3-chloroaniline, 3-bromoaniline, 3-trifluoromethoxy aniline, 3-nitroaniline, methyl 3-aminobenzoate, 3-cyanoaniline, 3-methylaniline, 4-fluoroaniline, 4-chloroaniline, 4-bromoaniline, 4-iodoaniline, 4-trifluoromethoxy aniline, 4-trifluoromethylaniline, methyl 4-aminobenzoate, 4-methylsulfonylaniline, 4-nitroaniline, 4-cyanoaniline, 4-phenylaniline, 4-methylaniline, 4-tert-butylaniline, 4-phenoxyaniline, 4-methoxyaniline, 4-hydroxyaniline, 2-phenylaniline, 3-fluoroaniline, 3-chloroaniline, 3-bromoaniline, 4-trifluoromethylaniline, 4-methylsulfanylaniline, 4-nitroaniline, 4, 4-piperidyl aniline and 4-nitro-1-aniline.
Preferably, in the method of the present invention, the α -hydroxyaryl ethanones have the general formula IV:
Figure BSA0000178383840000053
R4selected from: hydrogen atom, halogen atom, C1-C10Linear or branched alkyl, alkoxy, substituted or unsubstituted C6-C10One of aryl and nitro;
Ar2selected from: c6-C10One of aryl groups.
Preferably, in the method of the present invention, the α -hydroxyaryl ethanones are selected from: one of alpha-hydroxyacetophenone, alpha-hydroxy-4-methylacetophenone, alpha-hydroxy-4-methoxyacetophenone, alpha-hydroxy-4-phenylacetophenone, alpha-hydroxy-4-fluoroacetophenone, alpha-hydroxy-3-chloroacetophenone, alpha-hydroxy-3-bromoacetophenone, alpha-hydroxy-3-nitroacetophenone and alpha-hydroxy-2-naphthylacetophenone.
The general formula of the reaction system synthesized by the 1, 2-diaryl indole and the derivative thereof provided by the invention is formed by I, II, III and IV, and is as follows:
Figure BSA0000178383840000061
the method comprises the following steps:
(1) adding an iodine reagent, a cyclic ketone compound, an aromatic amine compound and an alpha-hydroxy aryl ethanone compound into a reaction container;
(2) replacing air in the reaction container with oxygen, adding a secondary amine, a sulfoxide or sulfone reagent and an organic solvent, sealing, stirring and heating;
(3) after the reaction is finished, separating and purifying to obtain the target product.
The secondary amine is selected from: one or more of N-methylisopropylamine, N-methylbenzylamine, N-methylaniline, N-methylcyclohexylamine, phthalimide, succinimide, cyclohexylimine, tetrahydropyrrole, tetrahydroisoquinoline, indoline, morpholine, thiomorpholine, piperazine, N-methylpiperazine, N-methyl-2-methylpiperazine, piperidine, 4-methylpiperidine, 3, 5-dimethylpiperidine and 3-methylpiperidine;
preferably: a morpholine;
the iodine reagent is selected from: sodium periodate (NaIO)4) Potassium iodide (KI), ammonium iodide (NH4I), sodium iodide (NaI), Hydrogen Iodide (HI), iodobenzene (PhI), iodobenzene Diacetate (DAIB), elemental iodine (I)2) And N-iodosuccinimide (NIS);
preferably: potassium iodide (KI);
the sulfoxide or sulfone reagent is selected from: one or more of dimethyl sulfoxide (DMSO), diphenyl sulfoxide, sulfolane, dimethyl sulfone, diphenyl sulfone and phenyl benzyl sulfone;
preferably: dimethyl sulfoxide (DMSO);
the organic solvent is selected from: o-xylene (o-xylene), p-xylene (p-xylene), m-xylene (m-xylene), trifluorotoluene (PhCF)3) Toluene (PhCH)3) Chlorobenzene (PhCl), 1, 2-Dichloroethane (DCE), cyclohexane and n-octane;
preferably: toluene (PhCH)3)：
The molar ratio of the cyclic ketone compound, the aromatic amine compound, the alpha-hydroxy aryl ethanone compound, the secondary amine, the iodine reagent and the sulfoxide (or sulfone) reagent is 1-3: 1-2: 0.1-1: 1-4; the reaction temperature is 100-160 ℃; the reaction time is 4-24 h.
Preferably: the mol ratio is 1.5: 1: 1.25: 0.2: 2: the reaction temperature is 150 ℃; the reaction time was 12 h.
The invention can be obtained from the general formula of the reaction system for synthesizing the 1, 2-diaryl indole and the derivatives thereof, and the invention is a technical scheme for efficiently and greenly generating the 1, 2-diaryl indole and the derivatives thereof by a cyclic ketone compound, an aromatic amine compound and an alpha-hydroxy aryl ethanone compound under the promotion of secondary amine, an iodine reagent and a sulfoxide (or sulfone) reagent and in an oxygen atmosphere.
Table: reactants, reaction conditions and yields of examples 1-46 (all reactions were carried out under oxygen atmosphere)
Figure BSA0000178383840000071
Figure BSA0000178383840000081
Figure BSA0000178383840000091
Figure BSA0000178383840000101
Figure BSA0000178383840000111
The nuclear magnetism, mass spectrum and other characterization data of the compounds of some examples of the invention:
the nuclear magnetic and mass spectral data of the product of example 1 are as follows:
Figure BSA0000178383840000112
1H NMR(400MHz，CDCl3)δ7.49(s，1H)，7.42-7.36(m，2H)，7.34-7.29(m，1H)，7.27-7.19(m，8H)，7.03(dd，J＝8.4，1.6Hz，1H)，6.74(s，1H)，2.76(q，J＝7.6Hz，2H)，1.30(t，J＝7.6Hz，3H).13C NMR(100MHz，CDCl3)δ 140.7，138.7，137.5，136.8，132.6，129.2，128.8，128.4，128.1，127.9，127.1，127.0，122.9，118.9，110.4，103.4，29.0， 16.5：HRMS(ESI)m/z：calcd for：C22H20N+(M+H)+298.1590，Found：298.1595.
the nuclear magnetic and mass spectral data of the product of example 2 are as follows:
Figure BSA0000178383840000113
1H NMR(400MHz，CDCl3)δ7.47(s，1H)，7.41-7.35(m，2H)，7.34-7.30(m，1H)，7.27-7.19(m，8H)，7.01(dd，J＝ 8.4，1.6Hz，1H)，6.74(s，1H)，2.75-2.64(m，2H)，1.75-1.65(m，2H)，0.97(t，J＝7.3Hz，3H).13C NMR(100MHz， CDCl3)δ140.7，138.7，137.6，135.1，132.7，129.2，128.8，128.4，128.1，127.9，127.1，127.0，123.4，119.6，110.3， 103.4，38.1，25.3，13.9；HRMS(ESI)m/z：calcd for：C23H22N+(M+H)+312.1747，Found：312.1749.
the nuclear magnetic and mass spectral data of the product of example 5 are as follows:
Figure BSA0000178383840000114
1H NMR(400MHz，CDCl3)δ7.63(s，1H)，7.42-7.38(m，2H)，7.35-7.31(m，1H)，7.25-7.18(m，9H)，6.77(s，1H)， 1.72(q，J＝7.4Hz，2H)，1.37(s，6H)，0.73(t，J＝7.4Hz，3H).13C NMR(100MHz，CDCl3)δ141.9，140.6，138.7， 137.1，132.7，129.1，128.8，128.1，128.0，127.9，127.1，126.9，121.1，117.4，110.0，103.8，37.8，37.1，29.0，9.3； HRMS(ESI)m/z：calcd for：C25H26N+(M+H)+340.2060，Found：340.2062.
the nuclear magnetic and mass spectral data of the product of example 8 are as follows:
Figure BSA0000178383840000121
1H NMR(400MHz，CDCl3)δ8.46-8.45(m，1H)，7.89-7.87(m，1H)，7.45-7.35(m，3H)，7.29-7.23(m，8H)， 6.89-6.85(m，1H)，4.41(q，J＝7.1Hz，2H)，1.43(t，J＝7.1Hz，3H).13C NMR(100MHz，CDCl3)δ167.5，142.1， 141.3，137.9，131.9，129.4，128.9，128.2，127.9，127.7，127.6，123.6，123.3，123.0，110.2，104.5，60.6，14.4；HRMS (ESI)m/z：calcd for：C23H20NO2 +(M+H)+342.1489，Found：342.1494.
the nuclear magnetic and mass spectral data of the product of example 9 are as follows:
Figure BSA0000178383840000122
1H NMR(400MHz，CDCl3)δ7.89(s，1H)，，7.68-7.66(m，2H)，7.47-7.39(m，5H)，7.37-7.31(m，3H)，7.30-7.22 (m，7H)，6.85(s，1H).13C NMR(100MHz，CDCl3)δ142.4，141.4，138.5，138.4，134.3，132.4，129.3，128.9，128.7， 128.6，128.2，127.9，127.4，127.2，126.4，122.1，119.0，110.8，104.0；HRMS(ESI)m/z：calcd for：C26H20N+ (M+H)+346.1590.Found：346.1595.
the nuclear magnetic and mass spectral data of the product of example 10 are as follows:
Figure BSA0000178383840000123
1H NMR(400MHz，CDCl3)δ7.82(d，J＝0.9Hz，1H)，7.54-7.52(m，2H)，7.45-7.39(m，2H)，7.38-7.31(m，3H)， 730-7.22(m，7H)，6.92-6.90(m，2H)，6.83(s，1H).The peak of the hydroxyl group did not appeared.13C NMR (101MHz，CDCl3)δ154.5，141.3，138.5，138.2，135.1，133.9，132.4，129.3，128.9，128.7，128.5，128.2，127.9， 127.3，127.2，121.9，118.5，115.5，110.8，103.9；HRMS(ESI)m/z：calcd for：C26H20NO+(M+H)+362.1539，Found 362.1541.
the nuclear magnetic and mass spectral data of the product of example 11 are as follows:
Figure BSA0000178383840000124
1H NMR(400MHz，CDCl3)δ7.56(d，J＝8.0Hz，1H)，7.42-7.39(m，2H)，7.35-7.31(m，1H)，7.25-7.18(m，7H)， 7.08(s，1H)，7.01(d，J＝8.0Hz，1H)，6.75(s，1H)，2.42(s，3H).13C NMR(100MHz，CDCl3)δ140.1，139.4， 138.6，132.6，132.2，129.2，128.8，128.7，128.1，128.0，127.0，126.0，122.4，120.2，110.4，103.6，21.9；HRMS(ESI) m/z：calcd for：C21H18N+(M+H)+，284.1433.Found：284.1434.
the nuclear magnetic and mass spectral data of the product of example 12 are as follows:
Figure BSA0000178383840000125
1H NMR(400MHz，CDCl3)δ8.31(d，J＝8.2Hz，1H)，7.90(d，J＝8.1Hz，1H)，7.60-7.56(m，2H)，7.48-7.36(m， 5H)，7.34-7.20(m，8H).13C NMR(100MHz，CDCl3)δ139.0，138.3，135.4，132.6，129.6，129.3，128.8，128.5，128.2，127.9，127.5，127.0，125.9，123.6，123.3，123.1，123.0，112.2，102.7；HRMS(ESI)m/z：calcd for：C24H18N+ (M+H)+320.1434，Found：320.1438.
the nuclear magnetic and mass spectral data of the product of example 13 are as follows:
Figure BSA0000178383840000131
1H NMR(400MHz，CDCl3)δ8.17(d，J＝8.7Hz，1H)，8.05(d，J＝1.9Hz，1H)，7.64(dd，J＝8.7，1.9Hz，1H)， 7.48-7.39(m，5H)，7.32-7.24(m，8H).13C NMR(100MHz，CDCl3)δ139.5，138.1，135.5，132.3，130.9，130.5，129.4，128.9，128.8，128.2，128.1，127.7，127.3，126.4，124.8，123.2，122.0，117.1，113.3，102.5；HRMS(ESI)m/z： calcd for：C24H17BrN+(M+H)+398.0539，Found：398.0540.
the nuclear magnetic and mass spectral data of the product of example 15 are as follows:
Figure BSA0000178383840000132
1H NMR(400MHz，CDCl3)δ7.79(d，J＝8.9Hz，1H)，7.62(d，J＝2.5Hz，1H)，7.49(d，J＝8.9Hz，1H)， 7.45-7.36(m，3H)，7.32-7.20(m，9H)，7.09(dd，J＝8.8，2.5Hz，1H)，4.00(s，3H).13C NMR(100MHz，CDCl3)δ 158.0，138.7，138.4，135.9，132.6，130.1，129.3，129.0，128.7，128.1，127.5，127.0，124.5，123.0，122.7，115.1， 109.8，102.7，102.7，55.4；HRMS(ESI)m/z：calcd for：C25H20NO+(M+H)+350.1539，Found：350.1539.
the nuclear magnetic and mass spectral data of the product of example 17 are as follows:
Figure BSA0000178383840000133
1H NMR(400MHz，CDCl3)δ7.47(s，1H)，7.35-7.31(m，1H)，7.30-7.21(m，6H)，7.19-7.13(m，2H)，7.06-6.95 (m，2H)，6.74(s，1H)，2.46(s，3H).13C NMR(100MHz，CDCl3)δ158.0(d，JC-F＝251.7Hz)，141.3，137.5，132.4， 130.4，130.1，129.3(d，JC-F＝7.6Hz)，128.7，128.3，128.2，127.4，126.6(d，JC-F＝12.7Hz)，124.5(d，JC-F＝3.9Hz)， 124.0，120.3，116.8(d，JC-F＝19.8Hz)，110.2(d，JC-F＝0.8Hz)，103.4，21.4；HRMS(ESI)m/z：calcd for： C21H17NF+(M+H)+302.1339，Found：302.1342.
the nuclear magnetic and mass spectral data of the product of example 18 are as follows:
Figure BSA0000178383840000134
1H NMR(400MHz，CDCl3)δ7.48(s，1H)，7.31-7.24(m，6H)，7.22-7.17(m，3H)，6.98-6.96(m，1H)，6.85-6.82 (m，1H)，6.76-6.75(m，1H)，2.46(s，3H)，1.86(s，3H).13C NMR(100MHz，CDCl3)δ141.1，137.7，137.4，136.9， 132.8，131.1，129.6，129.5，128.4，128.3，128.2，128.1，127.2，126.8，123.7.120.1，110.4，102.1，21.4，17.5；HRMS (ESI)m/z：calcd for：C22H20N+(M+H+)298.1590.Found：298.1597.
the nuclear magnetic and mass spectral data of the product of example 19 are as follows:
Figure BSA0000178383840000135
1H NMR(400MHz，CDCl3)δ7.67-7.65(m，1H)，7.53(td，J＝7.6，1.6Hz，1H)，7.46(td，J＝7.5，1.3Hz，1H)，7.42 (s，1H)，7.35(dd，J＝7.6，1.4Hz，1H)，7.20(d，J＝8.3Hz，1H)，7.11-6.99(m，5H)，6.93-6.89(m，2H)，6.73-6.71 (m，2H)，6.45(s，1H)，6.37-6.32(m，2H)，2.48(s，3H).13C NMR(100MHz，CDCl3)δ141.1，140.5，138.3，137.5， 136.0，132.5，131.3，129.6，129.5，128.5，128.2，128.1，127.9，127.8，127.7，127.6，126.7，126.6，123.7，120.1， 110.4，102.2.21.5；HRMS(ESI)m/z：calcd for：C27H22N+(M+H)+360.1747，found 360.1749.
the nuclear magnetic and mass spectral data of the product of example 20 are as follows:
Figure BSA0000178383840000141
1H NMR(400MHz，CDCl3)δ7.45(s，1H)，7.31-7.27(m，3H)，7.25-7.21(m，5H)，7.18(d，J＝8.4Hz，1H)， 7.06-7.00(m，2H)，6.71(s，1H)，2.46(s，3H).13C NMR(100MHz，CDCl3)δ140.5，139.9，137.2，134.6，132.2， 130.3，130.1，128.8，128.6，128.2，127.9，127.4，127.2，126.2，124.2，120.3，110.0，104.0，21.4；HRMS(ESI)m/z： calcd for：C21H17ClN+(M+H)+318.1044，Found：318.1047.
the nuclear magnetic and mass spectral data of the product of example 21 are as follows:
Figure BSA0000178383840000142
1H NMR(400MHz，CDCl3)δ7.48-7.44(m，3H)，7.25-7.17(m，7H)，7.08(d，J＝8.0Hz，1H)，7.02(d，J＝8.4Hz， 1H).6.71(s，1H)，2.46(s，3H).13C NMR(100MHz，CDCl3)δ140.6，140.0，137.2，132.2，130.7，130.4，130.4， 130.1，128.8，128.6，128.3，127.4，126.7，124.2，122.5，120.3，110.0，104.0，21.4；HRMS(ESI)m/z：calcd for： C21H17BrN+(M+H)+362.0539，Found：362.0541.
the nuclear magnetic and mass spectral data of the product of example 22 are as follows:
Figure BSA0000178383840000143
1H NMR(400MHz，CDCl3)δ7.47(s，1H)，7.41(t，J＝8.1Hz，1H)，7.25-7.16(m，8H)，7.09(s，1H)，7.03(d，J＝ 8.4Hz，1H).6.73(s，1H)，2.47(s，3H).13C NMR(100MHz，CDCl3)δ149.5(q，JC-F＝2.0Hz)，140.6，140.1，137.0， 132.2，130.5，130.2，128.9，128.7，128.3，127.5，126.1，124.3，120.6，120.4，120.3(q，JC-F＝258.0Hz)，119.3，109.9， 104.2，21.4；HRMS(ESI)m/z：calcd for：C22H17F3NO+(M+H)+368.1257，Found：368.1257.
the nuclear magnetic and mass spectral data of the product of example 23 are as follows:
Figure BSA0000178383840000144
1H NMR(400MHz，CDCl3)δ8.19-8.15(m，2H)，7.56-7.51(m，1H)，7.49-7.45(m，2H)，7.27-7.18(m，6H)， 7.07-7.04(m，1H)，6.76(s，1H)，2.47(s，3H).13C NMR(100MHz，CDCl3)δ148.7，140.5，140.0，137.0，133.8，131.8，130.9，130.0，128.9，128.8，128.4，127.7，124.6，122.4，121.6，120.6，109.6，104.9，21.3；HRMS(ESI)m/z： calcd for：C21H17N2O2 +(M+H)+329.1284，Found：329.1285.
the nuclear magnetic and mass spectral data of the product of example 24 are as follows:
Figure BSA0000178383840000151
1H NMR(400MHz，CDCl3)δ8.05(m，1H)，8.02-8.00(m，1H)，7.44(m，2H)，7.30-7.27(m，1H)，7.25-7.22(m， 5H)，7.16(d，J＝8.4Hz，1H)，7.02-7.00(m，1H)，6.73(s，1H)，3.90(s，3H)，2.47(s，3H).13C NMR(100MHz， CDCl3)δ166.2，140.6，139.0，137.3，132.4，132.2，131.3，130.2，129.3，128.8，128.6，128.6，128.2，128.0，127.3， 124.1，120.3，110.0，103.8，52.3，21.3；HRMS(ESI)m/z：calcd for：C23H20NO2 +(M+H)+342.1489，found 342.1490.
the nuclear magnetic and mass spectral data of the product of example 25 are as follows:
Figure BSA0000178383840000152
1H NMR(400MHz，CDCl3)δ7.60(d，J＝7.6Hz，1H)，7.54(s，1H)，7.51-7.46(m，2H)，7.42(d，J＝8.2Hz，1H)， 7.27-7.24(m，3H)，7.21-7.18(m，2H)，7.15(d，J＝8.4Hz，1H)，7.04(d，J＝8.4Hz，1H)，6.74(s，1H)，2.47(s，3H). 13C NMR(100MHz，CDCl3)δ140.4，139.7，136.9，132.3，131.8，130.9，130.8，130.4，130.2，128.8，128.7，128.4， 127.7，124.5，120.5，117.9，113.4，109.6，104.7，21.3；HRMS(ESI)m/z：calcd for：C22H17N2 +(M+H)+309.1386， Found：309.1389.
the nuclear magnetic and mass spectral data of the product of example 26 are as follows:
Figure BSA0000178383840000153
1H NMR(400MHz，CDCl3)δ7.71(d，J＝8.5Hz，2H)，7.46(s，1H)，7.29-7.24(m，5H)，7.17(d，J＝8.4Hz，1H)， 7.02-6.97(m.3H)，6.71(s，1H)，2.46(s，3H).13C NMR(100MHz，CDCl3)δ140.4，138.4，138.3，137.1，132.3， 130.3，129.6，128.8，128.6，128.3，127.4，124.1，120.3，110.0，103.9，91.9，2114；HRMS(ESI)m/z：calcd for： C21H17IN+(M+H)+410.0400，Found：410.0402.
the nuclear magnetic and mass spectral data of the product of example 27 are as follows:
Figure BSA0000178383840000154
1H NMR(400MHz，CDCl3)δ7.65(d，J＝8.2Hz，2H)，7.47(s，1H)，7.35-7.32(m，2H)，7.26-7.20(m，6H)，7.03(d， J＝8.4Hz，1H)，6.74(s，1H)，2.47(s，3H).13C NMR(100MHz，CDCl3)δ141.9，140.5，137.0，132.2，130.6，128.9， 128.8，128.6，128.3，127.9，127.5，126.3(q，JCF＝3.7Hz)，124.4，123.9(q，JCF＝272.1Hz)，120.5，109.9，104.6， 21.3；HRMS(ESI)m/z：calcd for：C22H17F3N+(M+H)+352.1308，Found：352.1309.
the nuclear magnetic and mass spectral data of the product of example 28 are as follows:
Figure BSA0000178383840000155
1H NMR(400MHz，CDCl3)δ7.98-7.94(m，2H)，7.48(s，1H)，7.42-7.39(m，2H)，7.28-7.19(m，6H)，7.05(d，J＝ 8.4Hz，1H)，6.75(s，1H)，3.10(s，3H)，2.47(s，3H).13C NMR(100MHz，CDCl3)δ143.5，140.3，138.2，136.6， 131.8，130.8，128.9，128.8，128.5，128.4，128.1，127.6，124.5，120.6，109.7，105.2，44.4，21.3；HRMS(ESI)m/z： calcd for：C22H20NO2S+(M+H)+362.1209，Found：362.1212.
the nuclear magnetic and mass spectral data of the product of example 30 are as follows:
Figure BSA0000178383840000161
1H NMR(400MHz，CDCl3)δ7.46(s，1H)，7.28-7.20(m，5H)，7.13-7.07(m，3H)，6.99(d，J＝8.4Hz，1H)， 6.85-6.80(m，2H)，6.70(s，1H)，5.11(s，1H)，2.46(s，3H).13C NMR(100MHz，CDCl3)δ154.5，140.8，137.8， 132.6，131.6，129.8，129.2，128.8，128.3，128.1，127.1，123.8，120.1，116.0，110.3，102.7，21.4.；HRMS(ESI)m/z： calcd for：C21H18NO+(M+H)+300.1383，found 300.1386.
the nuclear magnetic and mass spectral data of the product of example 31 are as follows:
Figure BSA0000178383840000162
1H NMR(400MHz，CDCl3)δ7.46(s，1H)，7.39-7.35(m，2H)，7.27-7.23(m，5H)，7.19-7.13(m，4H)，7.07-7.00 (m，5H)，6.71(s，1H)，2.47(s，3H).13C NMR(100MHz，CDCl3)δ156.7，156.2，140.8，137.6，133.6，132.6，129.9， 129.9，129.2，128.8，128.4，128.1，127.2，123.9，123.7，120.2，119.2，119.0，110.2，103.1，21.4.HRMS(ESI)m/z： calcd for：C27H22NO+(M+H)+376.1696，Found：376.1696.
the nuclear magnetic and mass spectral data of the product of example 33 are as follows:
Figure BSA0000178383840000163
1H NMR(400MHz，CDCl3)δ7.44(s，1H)，7.31-7.27(m，2H)，7.24-7.18(m，3H)，7.15-7.07(m，3H)，6.97(dd，J＝ 8.4，1.2Hz，1H)，6.96-6.88(m，2H)，6.68(s，1H)，3.22-3.16(m，4H)，2.45(s，3H)，1.74-1.69(m，4H)，1.62-1.56(m， 2H).13C NMR(100MHz，CDCl3)δ150.9，140.8，137.9，132.9，129.8，129.6，128.8，128.5，128.2，128.0，126.9， 123.6，120.0，116.4，110.5，102.4，50.3，25.8，24.2，21.4；HRMS(ESI)m/z：calcd for：C26H27N2 +(M+H)+367.2169， Found：367.2171.
the nuclear magnetic and mass spectral data of the product of example 34 are as follows:
Figure BSA0000178383840000164
1H NMR(400MHz，CDCl3)δ8.64(d，J＝8.8Hz，1H)，8.18(d，J＝8.1Hz，1H)，7.77-7.71(m，2H)，7.56-7.51(m，2H).7.29(d，J＝8.1Hz，1H)，7.19-7.13(m，5H)，6.93(dd，J＝8.4，1.1Hz，1H)，6.89(s，1H)，6.66(d，J＝8.4Hz， 1H)，2.47(s，3H).13C NMR(100MHz，CDCl3)δ145.9，142.1，141.4，138.5，131.9，131.9，130.7，130.0，128.8， 128.4，128.4，128.1，127.7，126.1，125.5，124.7，124.4，123.8，123.6，120.5，110.6，104.4，21.4；HRMS(ESI)m/z： calcd for：C25H19N2O2 +(M+H)+379.1441，Found：379.1443.
the nuclear magnetic and mass spectral data of the product of example 35 are as follows:
Figure BSA0000178383840000171
1H NMR(400MHz，CDCl3)δ7.45(s，1H)，7.41-7.37(m，2H)，7.33-7.29(m，1H)，7.24-7.21(m，2H)，7.18-7.13 (m.3H)，7.03(d，J＝8.0Hz，2H).6.98(dd，J＝8.4，0.9Hz，1H)，6.68(s，1H)，2.45(s，3H)，2.29(s，3H).13C NMR (100MHz，CDCl3)δ140.8，138.8，137.4，137.0，129.9，129.7，129.2，128.8，128.7，128.5，128.0，126.9，123.7，120.0，110.2，102.9，21.4，21.2；HRMS(ESI)m/z：calcd for：C22H20N+(M+H+)298.1590，Found：298.1597.
the nuclear magnetic and mass spectral data of the product of example 36 are as follows:
Figure BSA0000178383840000172
1H NMR(400MHz，CDCl3)δ7.44(s，1H)，7.41-7.38(m，2H)，7.34-7.30(m，1H)，7.24-7.21(m，2H)，7.18-7.14 (m，3H)，6.99-6.96(m，1H)，6.78-6.75(m，2H)，6.64(s，1H)，3.76(s，3H)，2.46(s，3H).13C NMR(100MHz， CDCl3)δ158.8，140.6，138.8，137.2，130.0，129.9，129.2，128.6，128.0，126.9，125.2，123.5，119.9，113.6，110.2，102.4，55.2，21.4；HRMS(ESI)m/z：calcd for：C22H20NO+(M+H)+314.1539，Found：314.1541.
the nuclear magnetic and mass spectral data of the product of example 37 are as follows:
Figure BSA0000178383840000173
1H NMR(400MHz，CDCl3)δ7.58-7.54(m，2H)，7.48-7.26(m，13H)，7.19(d，J＝8.4Hz，1H)，7.01(dd，J＝8.4， 1.2Hz，1H)，6.78(s，1H)，2.47(s，3H).13C NMR(100MHz，CDCl3)δ140.4，140.3，139.7，138.7，137.6，131.6， 130.0，129.3，129.0，128.7，128.5，128.0，127.3，127.1，126.9，126.8，124.0，120.2，110.3，103.4，21.4；HRMS(ESI) m/z：calcd for：C27H22N+(M+H)+360.1747，found 360.1749.
the nuclear magnetic and mass spectral data of the product of example 38 are as follows:
Figure BSA0000178383840000174
1H NMR(400MHz，CDCl3)δ7.46(s，1H)，7.42-7.38(m，2H)，7.35-7.32(m，1H)，7.24-7.15(m，5H)，7.02-6.98 (m，1H)，6.96-6.88(m，2H)，6.67(s，1H)，2.46(s，3H).13C NMR(101MHz，CDCl3)δ162.0(d，JC-F＝247.3Hz)， 139.7，138.5，137.4，130.5(d，JC-F＝8.0Hz)，130.1，129.3，128.8(d，JC-F＝2.9Hz)，128.4，127.9，127.1，124.0， 120.1，115.2(d，JC-F＝21.6Hz)，110.3，103.2，21.4；HRMS(ESI)m/z：calcd for：C21H17NF+(M+H)+302.1339， Found：302.1342.
the nuclear magnetic and mass spectral data of the product of example 39 are as follows:
Figure BSA0000178383840000175
1H NMR(400MHz，CDCl3)δ7.46(s，1H)，7.44-7.40(m，2H)，7.37-7.33(m，1H)，7.32-7.30(m，1H)，7.24-7.21 (m，2H)，7.19-7.16(m，2H)，7.12(t，J＝7.8Hz，1H)，7.05-7.00(m，2H)，6.74(s，1H)，2.46(s，3H).13C NMR(100 MHz，CDCl3)δ139.0，138.3，137.6，134.4，134.0，130.2，129.3，129.3，128.6，128.3，127.9，127.3，127.1，126.8， 124.4，120.3，110.4，104.0，21.4；HRMS(ESI)m/z：calcd for：C21H17ClN+(M+H)+318.1044，Found：318.1047.
the nuclear magnetic and mass spectral data of the product of example 40 are as follows:
Figure BSA0000178383840000181
1H NMR(400MHz，CDCl3)δ7.48-7.45(m，2H)，7.43-7.40(m，2H)，7.37-7.30(m，2H)，7.23-7.20(m，2H)， 7.19-7.16(m.1H)，7.07-7.00(m，3H)，6.73(s，1H)，2.46(s，3H).13C NMR(100MHz，CDCl3)δ138.9，138.3， 137.6，134.7，131.5，130.2，130.0，129.5，129.3，128.3，127.9，127.3，127.2，124.4，122.2，120.3，110.4，104.0，21.4； HRMS(ESI)m/z：calcd for：C21H17BrN+(M+H)+362.0539，Found：362.0541.
the nuclear magnetic and mass spectral data of the product of example 41 are as follows:
Figure BSA0000178383840000182
1H NMR(400MHz，CDCl3)δ8.19-8.15(m，1H)，8.07-8.02(m，1H)，7.51-7.47(m，2H)，7.46-7.42(m，2H)， 7.40-7.35(m，2H)，7.26-7.22(m，2H)，7.21-7.16(m，1H)，7.08-7.03(m，1H)，6.85(s，1H)，2.47(s，3H).13C NMR (100MHz，CDCl3)δ148.1，138.0，137.9，137.7，134.3，134.2，130.5，129.6，129.0，128.1，127.9，127.7，124.9， 123.2，121.7，120.5，110.5，104.8，21.4；HRMS(ESI)m/z：calcd for：C21H17N2O2 +(M+H)+329.1284，Found： 329.1285.
the nuclear magnetic and mass spectral data of the product of example 42 are as follows:
Figure BSA0000178383840000183
1H NMR(400MHz，CDCl3)δ7.77-7.73(m，2H)，7.69-7.64(m，2H)，7.49(s，1H)，7.44-7.36(m，4H)，7.34-7.30 (m，2H)，7.29-7.27(m，2H)，7.24-7.20(m，1H)，7.02(dd，J＝8.4，1.1Hz，1H)，6.84(s，1H)，2.48(s，3H).13C NMR (100MHz，CDCl3)δ140.6，138.7，137.6，133.2，132.3，130.1，130.0，129.3，128.6，128.1，127.9，127.7，127.6， 127.5，127.1，126.7，126.2，126.0，124.0，120.2，110.3，103.8，21.4；HRMS(ESI)m/z：calcd for：C25H20N+(M+H)+ 334.1590，Found：334.1593.
the nuclear magnetic and mass spectral data of the product of example 44 are as follows:
Figure BSA0000178383840000184
1H NMR(400MHz，CDCl3)δ8.31(d，J＝8.2Hz，1H)，8.12(t，J＝1.7Hz，1H)，8.08(dt，J＝7.8，1.3Hz，1H)， 7.91(d，J＝8.0Hz，1H)，7.61-7.57(m，2H)，7.51-7.43(m，2H)，7.40-7.33(m，3H)，7.31-7.23(m，5H)，3.92(s，3H). 13C NMR(100MHz，CDCl3)δ166.2，138.9，138.7，135.3，132.7，132.2，131.5，129.6，129.5，128.9，128.6，128.6， 128.3，127.8，127.2，126.0，123.8，123.4，123.0，111.8，103.2，52.4；HRMS(ESI)m/z：calcd for：C26H20NO2 + (M+H)+378.1489，Found：378.1489.
the nuclear magnetic and mass spectral data of the product of example 45 are as follows:
Figure BSA0000178383840000185
1H NMR(400MHz，CDCl3)δ8.43(d，J＝0.9Hz，1H)，7.89(dd，J＝8.7，1.5Hz，1H)，7.23-7.19(m，5H)， 7.16-7.11(m，2H)，6.99-6.95(m，2H)，6.82(s，1H)，3.95(s，3H).13C NMR(100MHz，CDCl3)δ168.1，162.3(d， JC-F＝248.5Hz)，161.7(d，JC-F＝248.5Hz)，141.2，141.1，133.6(d，JC-F＝3.2Hz)，130.6(d，JC-F＝8.2Hz)，129.5 (d，JC-F＝8.6Hz)，127.8(d，JC-F＝3.4Hz)，127.6，123.8，123.4，122.8，116.5(d，JC-F＝22.8Hz)，115.4(d，JC-F＝ 21.7Hz)，110.0，104.5，51.9；HRMS(ESI)m/z：calcd for：C22H16F2NO2 +(M+H)+364.1144，Found：364.1150.
the nuclear magnetic and mass spectral data of the product of example 46 are as follows:
Figure BSA0000178383840000191
1H NMR(400MHz，CDCl3)δ8.44(d，J＝1.2Hz，1H)，7.90(dd，J＝8.7，1.5Hz，1H)，7.23-7.19(m，5H)， 7.17-7.12(m，2H)，7.01-6.95(m，2H)，6.83(s，1H)，4.41(q，J＝7.1Hz，2H)，1.43(t，J＝7.1Hz，3H).13C NMR (100MHz，CDCl3)δ167.4，162.4(d，JC-F＝248.5Hz)，161.7(d，JC-F＝248.6Hz)，141.3，141.1，133.7(d，JC-F＝ 3.2Hz)，130.7(d，JC-F＝8.2Hz)，129.6(d，JC-F＝8.6Hz)，127.8(d，JC-F＝3.4Hz)，127.6，123.9，123.4，123.3， 116.5(d，JC-F＝22.8Hz)，115.4(d，JC-F＝21.7Hz)，110.0，104.5，60.7，14.4；HRMS(ESI)m/z：calcd for： C23H18F2NO2 +(M+H)+378.1300，Found：378.1305.
in order to show the practical values of the 1, 2-diaryl indole and the derivative thereof provided by the invention and the 1, 2-diaryl indole and the derivative thereof provided by the invention, the following two reaction formulas are shown:
Figure BSA0000178383840000192
by means of the synthesis method of the 1, 2-diaryl indole and the derivative thereof, the invention can also provide the 1, 2-diaryl indole and the derivative thereof which have great application value in the synthesis of bioactive molecules, and take the 1, 2-diaryl indole derivatives in the reaction formula 1 and the reaction formula 2 as examples.
Equation 1 reveals that the product of example 44 can be hydrolyzed in a simple step to obtain an inhibitor of beta-amyloid secretion.
Equation 2 reveals that the products of examples 45 and 46 can be hydrolyzed in a single step to provide an inhibitor of PASK activity.
The following references demonstrate the pharmaceutical value of the hydrolyzed molecules.
[1]Slade，R.；Klimova，Y.；Halter，R.；Yungai，A.；Weiner，W.；Walton，R.；Willardsen，J.；Anderson，M.； Zavitz，K.US 20080249135 A1，2008-10-09，2008.
[2]McCall，J.；Romero，D.；Clare，M.US 20120225846 A1，2012-09-06，2012.
The 1, 2-diaryl indole and the derivatives thereof provided by the invention have great application value for synthesis of bioactive molecules.
Compared with the traditional synthetic method, the synthetic method of the 1, 2-diaryl indole and the derivatives thereof provided by the invention has the following advantages:
(I) the used substrate and reagent have stable properties, are convenient to store, can be widely obtained, are cheap and easily available, and are beneficial to reducing the production cost;
(II) one-pot synthesis is carried out, multi-step operation is not needed, and the economic advantages of the steps are very obvious, so that the operability is good;
(III) the regioselectivity is excellent, and the 1, 2-diaryl indole derivative with a complex and changeable structure is prepared, so that the generation of isomers which are difficult to separate is avoided;
(IV) transition metal is not needed, thus fundamentally eliminating the pollution of the transition metal to the bioactive molecules of the final product;
(V) oxygen is used as a green oxidant in the reaction, so that the method is environment-friendly;
(VI) the whole reaction system is simple, reaction equipment is less, and experimental operation is simple and convenient, so that the method is beneficial to popularization and application.
Obviously, the above examples are only for clearly illustrating the 1, 2-diarylindole, the derivative and the synthetic method provided by the present invention, and are not intended to limit the embodiments. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. And are neither required nor exhaustive of all embodiments. And obvious variations or modifications of the invention may be made without departing from the spirit or scope of the invention.

Claims (1)

1. A method for synthesizing 1, 2-diaryl indole and its derivant is characterized in that cyclic ketone compound, aromatic amine compound, alpha-hydroxy aryl ethyl ketone compound, secondary amine, iodine reagent and sulfoxide or sulfone reagent are heated and stirred in organic solvent under oxygen atmosphere, and then separated and purified to obtain product 1, 2-diaryl indole and its derivant;
the secondary amine is selected from: one or more of N-methylisopropylamine, N-methylbenzylamine, N-methylaniline, N-methylcyclohexylamine, phthalimide, succinimide, cyclohexylimine, tetrahydropyrrole, tetrahydroisoquinoline, indoline, morpholine, thiomorpholine, piperazine, N-methylpiperazine, N-methyl-2-methylpiperazine, piperidine, 4-methylpiperidine, 3, 5-dimethylpiperidine and 3-methylpiperidine;
the iodine reagent is selected from: one or more of sodium periodate, potassium iodide, ammonium iodide, sodium iodide, hydrogen iodide, iodobenzene diacetate, elemental iodine and N-iodosuccinimide;
the sulfoxide or sulfone reagent is selected from: one or more of dimethyl sulfoxide, diphenyl sulfoxide, sulfolane, dimethyl sulfone, diphenyl sulfone and phenyl benzyl sulfone;
the organic solvent is selected from: one or more of o-xylene, p-xylene, m-xylene, trifluorotoluene, toluene, chlorobenzene, 1, 2-dichloroethane, cyclohexane and n-octane;
the molar ratio of the cyclic ketone compound, the aromatic amine compound, the alpha-hydroxy aryl ethanone compound, the secondary amine, the iodine reagent and the sulfoxide or sulfone reagent is 1-3: 1-2: 0.1-1: 1-4, the reaction temperature is 100-160 ℃, and the reaction time is 4-24 hours;
the cyclic ketone compound is selected from one of 4-methylcyclohexanone, 4-ethylcyclohexanone, 4-propylcyclohexanone, 4-isopropylcyclohexanone, 4-tert-butylcyclohexanone, 4-tert-amylcyclohexanone, 4-n-amylcyclohexanone, 4-cyclohexanone methyl formate, 4-cyclohexanone ethyl formate, 4-phenylcyclohexanone, 4- (4-hydroxyphenyl) cyclohexanone, 3-methylcyclohexanone, beta-tetralone, 6-bromo-beta-tetralone and 7-methoxy-beta-tetralone;
the aromatic amine compound is selected from: one of aniline, 2-fluoroaniline, 2-methylaniline, 2-phenylaniline, 3-chloroaniline, 3-bromoaniline, 3-trifluoromethoxyaniline, 3-nitroaniline, methyl 3-aminobenzoate, 3-cyanoaniline, 4-fluoroaniline, 4-chloroaniline, 4-iodoaniline, 4-trifluoromethylaniline, methyl 4-aminobenzoate, 4-methylsulfonylaniline, 4-phenylaniline, 4-tert-butylaniline, 4-phenoxyaniline, 4-methoxyaniline, 4-hydroxyaniline, 4-piperidinylaniline and 4-nitro-1-aniline;
the alpha-hydroxy aryl ethanone compound is selected from: one of alpha-hydroxyacetophenone, alpha-hydroxy-4-methylacetophenone, alpha-hydroxy-4-methoxyacetophenone, alpha-hydroxy-4-phenylacetophenone, alpha-hydroxy-4-fluoroacetophenone, alpha-hydroxy-3-chloroacetophenone, alpha-hydroxy-3-bromoacetophenone, alpha-hydroxy-3-nitroacetophenone, and alpha-hydroxy-2-naphthylacetophenone;
the structural formula of the 1, 2-diaryl indole and the derivative thereof is as follows:
Figure FSB0000192679270000011
Figure FSB0000192679270000021
Figure FSB0000192679270000031
Figure FSB0000192679270000041
Figure FSB0000192679270000051
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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1333206A (en) * 2000-07-11 2002-01-30 中国医学科学院药物研究所 Sulfuryl diphenyl indole compound and preparation process and use in medicine
CN101068781A (en) * 2004-10-04 2007-11-07 美瑞德生物工程公司 Compounds for alzheimer's disease
KR20140141004A (en) * 2013-05-31 2014-12-10 덕산하이메탈(주) Compound for organic electronic element, organic electronic element using the same, and an electronic device thereof
CN104703989A (en) * 2012-08-10 2015-06-10 株式会社斗山 Novel compound and organic electroluminescence device comprising same

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7678823B2 (en) * 2004-10-04 2010-03-16 Myriad Pharmaceticals, Inc. Compounds for alzheimer's disease
US20120225846A1 (en) * 2011-03-02 2012-09-06 Bioenergenix Heterocyclic compounds for the inhibition of pask

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1333206A (en) * 2000-07-11 2002-01-30 中国医学科学院药物研究所 Sulfuryl diphenyl indole compound and preparation process and use in medicine
CN101068781A (en) * 2004-10-04 2007-11-07 美瑞德生物工程公司 Compounds for alzheimer's disease
CN104703989A (en) * 2012-08-10 2015-06-10 株式会社斗山 Novel compound and organic electroluminescence device comprising same
KR20140141004A (en) * 2013-05-31 2014-12-10 덕산하이메탈(주) Compound for organic electronic element, organic electronic element using the same, and an electronic device thereof

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
A Visible-Light-Mediated Oxidative C-N Bond Formation/Aromatization Cascade: Photocatalytic Preparation of N-Arylindoles;Soumitra Maity等;《Angewandte Chemie, International Edition》;20120822;第51卷(第38期);9562-9566 *
Fabrication of an amyloid fibril-palladium nanocomposite: a sustainable catalyst for C–H activation and the electrooxidation of ethanol;Ramasamy Jayarajan等;《Journal of Materials Chemistry A: Materials for Energy and Sustainability》;20190114;第7卷(第9期);4486-4493 *
Modular Synthesis of Indoles from Imines and o-Dihaloarenes or o-Chlorosulfonates by a Pd-Catalyzed Cascade Process;José Barluenga等;《Journal of the American Chemical Society》;20090226;第131卷(第11期);4031-4041 *
Three-Component Cascade Reactions with 2,3-Diketoesters: A Novel Metal-Free Synthesis of 5-Vinyl-pyrrole and 4-Hydroxy-indole Derivatives;Qiang Sha等;《Organic Letters》;20150717;第17卷(第15期);3876-3879 *

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