CN108640945B - A kind of amide compound and its preparation method and application - Google Patents

Abstract

The invention relates to the technical field of organic synthesis, in particular to an amide compound and a preparation method and application thereof. The invention discloses a preparation method of an amide compound, comprising the following steps: in the presence of an inert solvent and under the action of a catalyst, The compound of formula (II) is reacted with the compound of formula (III) to obtain the compound of formula (I), the substrate of this method is simple and easy to obtain, and the alkynyl group of the direct carbon-hydrogen bond of ordinary primary and secondary amides without the assistance of additional guiding groups The chemical reaction has few steps, simple operation, high efficiency, good selectivity, economical and environmental protection, and at the same time, the method has a very wide application range to substrates and has good atom economy. The amide compound obtained by the preparation method is a brand new amide. It is widely used, and solves the technical problems of complex synthesis reaction of existing amide compounds and narrow substrate application range.

Description

A kind of amide compound and its preparation method and application

technical field

The invention relates to the technical field of organic synthesis, in particular to an amide compound and a preparation method and application thereof.

Background technique

Alkynes are a very common class of functional groups, found in everything from common simple synthetic building blocks to synthetic intermediates, biomolecules, and natural products. The ubiquity of carbon-carbon triple bonds has also stimulated long-standing research interest in this class of functional groups, including laboratory and industrial synthesis. Since the advent of the Sonogashira reaction catalyzed by palladium and copper synergistically in the 1970s, the synthesis of alkynes has made great progress, and has developed in the direction of atomic and step economy. As an important class of alkynes, o-amidoarylacetylenes can not only be used as key intermediates for the rapid synthesis of complex molecules through Diels-Alder reactions, but also the potential biological activities of heterocyclic substituted alkynyl-containing arylamides make this compounds have received extensive attention.

In recent years, the direct use of carbon-hydrogen bonds as starting materials for alkynylation has not only provided a new method to introduce and expand molecular complexity, but has also become a powerful strategy for the construction of structurally complex alkynes. However, to achieve regioselective direct alkynylation reactions utilizing C-H bonds, specific substrates are usually required, or additional directing groups are pre-installed into the molecule. For example, Su realized the oxidative coupling reaction of polyfluorinated benzene as starting material with terminal alkynes to construct polyfluorinated internal alkynes [Y.Wei,H.Zhao,J.Kan,W.Su,M.Hong,J . Am. Chem. Soc. 2010, 132, 2522.].

Transition metal-catalyzed activation of carbon-hydrogen bonds has developed rapidly. Based on transition metal-catalyzed carbon-hydrogen bond activation and functionalization reaction, the reaction process can be shortened, the atom economy can be improved, and the target products that are difficult to be prepared by conventional methods can be realized, which greatly promotes the development of synthetic methodologies for drug molecules and natural products. Recently, the preparation of multifunctional alkynes based on trivalent rhodium-catalyzed carbon-hydrogen bond activation strategy has been reported. In 2014, Loh, Li, Glorius et al. independently developed [RhCl ₂ Cp*] ₂ as a catalyst, arylamides substituted with additional directing groups, and nitrogen-containing heterocycles that could not be removed or further transformed through carbon-hydrogen bonds. Activation reacts with hypervalent iodine alkynylation reagents to achieve the synthesis of nitrogen-containing aryl and alkenyl substituted alkynes. Yu and Chatani, respectively, reported the palladium-catalyzed bidentate amide directing group, that is, the alkynylation reaction of alkane carbon-hydrogen bonds by an amide substrate with an additional directing group installed on the amide nitrogen atom. However, on the one hand, the reaction conditions of the above literature are relatively harsh (the substrate reaction scale is 0.1 mmol, 120 °C, 24 h), the substrate needs to be pre-installed with additional guiding groups and is difficult to convert or eliminate, and the reaction requires additional preparation difficulties And expensive hypervalent iodine alkynylation reagent (Waser reagent), therefore, this catalytic system obviously does not have practical and economic value, which limits the further application of this method; on the other hand, relative to nitrogen atom, oxygen The planarity of atoms is relatively poor, and the complexation effect of oxygen atoms on metals in amide compounds is weak, which also makes it difficult for subsequent functional groups to achieve high conversion even if such compounds are reversibly coordinated with metal catalysts , that is, the challenges faced by the alkynylation of carbon-hydrogen bonds of this type of compounds: difficult to coordinate and easy to dissociate.

Therefore, the synthesis methods of traditional amide compounds are often based on the coupling reaction of functional groups such as carbon-halogen bonds, or pre-installation of groups such as pyridine or quinoline on the amide nitrogen atom to promote the activity and regioselectivity of the reaction. The group is worthless in synthesis, and for subsequent practical application, it must be removed again at the end of the reaction. The traditional synthesis method is multi-step synthesis, the reaction is complex, and the scope of substrate application is narrow, etc., which makes them suitable for industrial applications. has been greatly restricted.

Therefore, developing a simple, efficient, economical, and industrially applicable amide compound and its preparation method is a technical problem that needs to be solved urgently at present.

SUMMARY OF THE INVENTION

The object of the present invention is to provide an amide compound and a preparation method and application thereof. The substrate of the method is simple and easy to obtain, has high efficiency, good selectivity, economical and environmental protection, and at the same time, the method has few steps, is easy to operate, and is suitable for the substrate. It has a very wide range, has good atomic economy, and has industrial application value. Its specific technical solutions are as follows:

The present invention also provides an amide compound.

Preferably, the amide compound has the structure represented by formula (I);

为C6～C14芳基、C4～C8含S、O的杂环或杂芳基；Among them, in formula (I)

is a C6-C14 aryl group, a C4-C8 heterocycle or a heteroaryl group containing S and O;

R ¹ is selected from hydrogen, C1-C4 saturated aliphatic hydrocarbon group, C1-C4 unsaturated aliphatic hydrocarbon group, methoxy, acetoxy, aryl, benzyl, benzenesulfonyl, -CR ⁷ C(O) ₂ R ⁸ or CR ⁹ R ¹⁰ OH;

R ² , R ³ , R ⁴ and R ⁵ are each independently selected from hydrogen, C1-C40 saturated aliphatic hydrocarbon group, C1-C40 unsaturated aliphatic hydrocarbon group, C1-C40 alkoxy group, C1-C40 alkylthio group, methylene Dioxy, halogenated C1-C40 saturated aliphatic hydrocarbon group, halogenated C1-C40 unsaturated aliphatic hydrocarbon group, halogenated C1-C40 alkoxy group, halogen, nitro, cyano, -CO ₂ R ⁷ , -OC(O)R ⁸ , -P(O)(R ⁹ )(R ¹⁰ ), -P(O)(OR ¹¹ )(OR ¹² ), -SO ₂ NR ¹³ R ¹⁴ , -NR ¹⁵ R ¹⁶ , -C(O)NR ¹⁷ R ¹⁸ , C6-C14 aryl, C6-C14 aryloxy, C1-C10 alkoxy, C2-C9 heteroaryl or C2-C9 heterocyclyl;

R ⁶ is selected from C1-C40 saturated hydrocarbon group, C1-C40 unsaturated hydrocarbon group, silicon group, C6-C14 aryl group, C2-C9 heterocyclic group;

R ⁷ and R ⁹ are each independently selected from hydrogen, C1-C40 saturated aliphatic hydrocarbon group, C1-C40 unsaturated aliphatic hydrocarbon group or aryl group;

R ⁸ and R ¹⁰ are each independently selected from C1-C40 saturated aliphatic hydrocarbon groups, C1-C40 unsaturated aliphatic hydrocarbon groups or aryl groups;

R ¹¹ , R ¹² , R ¹³ , R ¹⁴ , R ¹⁵ , and R ¹⁶ are each independently selected from hydrogen, C1-C40 saturated aliphatic hydrocarbon group, C1-C40 unsaturated aliphatic hydrocarbon group, C6-C14 aryl group, C2-C9 hetero group Aryl or C2-C9 heterocyclic group;

R ¹⁷ is selected from hydrogen, C1-C40 saturated aliphatic hydrocarbon group, C1-C40 unsaturated aliphatic hydrocarbon group, C6-C14 aryl group, C6-C14 arylsulfonyl group, C1-C10 alkylsulfonyl group, C1-C10 acyl group, C2-C9 heteroaryl or C2-C9 heterocyclyl;

R ¹⁸ is selected from hydrogen, C1-C40 saturated aliphatic hydrocarbon group, C1-C40 unsaturated aliphatic hydrocarbon group, C6-C14 aryl group, C6-C14 arylsulfonyl group, C1-C10 alkylsulfonyl group, C1-C10 acyl group , C2-C9 heteroaryl.

It should be noted that R ² , R ³ , R ⁴ , and R ⁵ may be independently selected from the above-mentioned groups, or the adjacent two groups of R ² , R ³ , R ⁴ , and R ⁵ may be the The carbon atoms connecting the two adjacent groups together form a C3-C6 cycloalkyl group or a C2-C9 heterocyclic group, that is, R ² , R ³ , R ⁴ , and R ⁵ only need to satisfy one of the above conditions.

Preferably, R ⁶ is selected from C1-C40 saturated or unsaturated hydrocarbon group, silicon group, C6-C14 aryl group, or C2-C9 heterocyclic group.

More preferably, R ⁶ is selected from a silicon group or a C1-C10 saturated or unsaturated hydrocarbon group, wherein the silicon group includes trimethylsilyl, triisopropylsilyl or methyldi-tert-butylsilyl.

Preferably, the C1-C40 saturated aliphatic hydrocarbon group is selected from C1-C40 alkyl groups.

Preferably, the C1-C40 unsaturated aliphatic hydrocarbon group is selected from C2-C40 alkenyl or C2-C40 alkynyl.

Preferably, the C6-C14 aryl group includes at least one first substituent;

The first substituent is selected from hydrogen, halogen, C1-C40 alkyl, C1-C10 acyl, C1-C40 alkoxy, trifluoromethyl, C6-C14 aryl, C2-C9 heteroaryl, substituted amine group, ester group, cyano group or phosphono group.

More preferably, the first substituent is selected from methyl, methoxy, trifluoromethyl, C6-C14 aryl, C2-C9 heteroaryl, -NR ¹⁵ R ¹⁶ , -CO ₂ R ⁷ , cyano, Halogen, -P(O)(R ¹¹ )(R ¹² ) or -P(O)(OR ¹¹ )(OR ¹² ).

More preferably, the first substituent is selected from halogen, C1-C40 alkyl, C1-C10 acyl or C1-C40 alkoxy.

Preferably, when the C6-C14 aryl group does not contain the first substituent, the C6-C14 aryl group is selected from phenyl or naphthyl.

More preferably, when the C6-C14 aryl group contains the first substituent, the C6-C14 aryl group is selected from phenyl, o-tolyl, o-methoxyphenyl, o-trifluoromethylphenyl, o-arylphenyl, o-heteroarylphenyl, o-substituted aminophenyl, o-ester phenyl, o-cyanophenyl, o-halophenyl, m-tolyl, m-methoxyphenyl, m-substituted aminophenyl, m Trifluoromethylphenyl, m-halophenyl, m-arylphenyl, m-heteroarylphenyl, m-esterylphenyl, m-cyanophenyl, p-tolyl, p-methoxyphenyl, p-substituted amine phenyl, p-trifluoromethylphenyl, p-halophenyl, p-esterylphenyl, p-cyanophenyl, p-arylphenyl and p-heteroarylphenyl, 2,3-bismethoxyphenyl Phenyl, 1-naphthyl, 2-naphthyl or phosphonophenyl.

Preferably, the aryl group, the C2-C9 heteroaryl group and the C2-C9 heterocyclic group all include at least one second substituent;

The second substituent is selected from halogen, C1-C40 alkyl, C1-C10 acyl or C1-C40 alkoxy.

Preferably, the C2-C9 heteroaryl group is selected from furanyl, benzofuranyl, thienyl, benzothienyl, nicotinic acid, isonicotinic acid, pyrrolyl, thiazolyl, oxazolyl, pyrazole group, imidazolyl, pyranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridyl, quinolinyl, isoquinolinyl or carbazolyl.

More preferably, the C2-C9 heteroaryl group is specifically selected from 2-furanyl, 3-furanyl, 2-benzofuranyl, 3-benzofuranyl, 2-thienyl, 3-thienyl, 2-benzene thienyl, 3-benzothienyl, 2-indolyl, 3-indolyl, 2-pyrrolyl, 3-pyrrolyl, 5-thiazolyl, 4-pyrazolyl, 3-pyridyl, 4 -pyridyl, 6-quinolinyl, 5-isoquinolinyl, 2-pyridyl, 2-quinolinyl, 2-pyrazinyl, 2-pyrimidinyl, 1-pyrazolyl or 2-thiazolyl.

Preferably, the C2-C9 heterocyclic group is selected from tetrahydroquinolinyl, N-acyltetrahydroquinolinyl, oxazolinyl, substituted oxazolinyl, tetrahydroindolyl, N-acyltetrahydro Indolyl, dihydropyrrolyl, tetrahydropyridyl, tetrahydrofuranyl, morpholinyl, piperazinyl, piperidinyl, pyrrolinyl or imidazolinyl.

More preferably, the C2-C9 heterocyclic group is selected from 6-tetrahydroquinolinyl, N-acyltetrahydroquinolinyl, 5-tetrahydroindolyl, N-acyltetrahydroindolyl, oxazolinyl , substituted oxazolinyl, tetrahydroquinolinyl, tetrahydroindolyl or 2-oxazolinyl.

The present invention also provides a preparation method of an amide compound, comprising the following steps:

In the presence of an inert solvent and under the action of a catalyst, the compound of formula (II) is reacted with the compound of formula (III) to obtain the compound of formula (I);

表示C6～C14芳基或C4～C8含S、O的杂环或杂芳基；Wherein, X is selected from hydrogen, bromine or iodine, when X is hydrogen, described reaction needs to add oxidizing agent, in formula (II)

Represents a C6-C14 aryl group or a C4-C8 heterocyclic or heteroaryl group containing S and O;

R ¹ is selected from hydrogen, C1-C4 saturated aliphatic hydrocarbon group, C1-C4 unsaturated aliphatic hydrocarbon group, methoxy, acetoxy, aryl, benzyl, benzenesulfonyl, -CR ⁷ C(O) ₂ R ⁸ or CR ⁹ R ¹⁰ OH;

R ² , R ³ , R ⁴ and R ⁵ are each independently selected from hydrogen, C1-C40 saturated aliphatic hydrocarbon group, C1-C40 unsaturated aliphatic hydrocarbon group, C1-C40 alkoxy group, C1-C40 alkylthio group, methylene Dioxy, halogenated C1-C40 saturated aliphatic hydrocarbon group, halogenated C1-C40 unsaturated aliphatic hydrocarbon group, halogenated C1-C40 alkoxy group, halogen, nitro, cyano, -CO ₂ R ⁷ , -OC(O)R ⁸ , -P(O)(R ⁹ )(R ¹⁰ ), -P(O)(OR ¹¹ )(OR ¹² ), -SO ₂ NR ¹³ R ¹⁴ , -NR ¹⁵ R ¹⁶ , -C(O)NR ¹⁷ R ¹⁸ , C6-C14 aryl, C6-C14 aryloxy, C1-C10 alkoxy, C2-C9 heteroaryl or C2-C9 heterocyclyl;

R ⁶ is selected from C1-C40 saturated hydrocarbon group, C1-C40 unsaturated hydrocarbon group, silicon group, C6-C14 aryl group, C2-C9 heterocyclic group;

R ⁷ and R ⁹ are each independently selected from hydrogen, C1-C40 saturated aliphatic hydrocarbon group, C1-C40 unsaturated aliphatic hydrocarbon group or aryl group;

R ⁸ and R ¹⁰ are each independently selected from C1-C40 saturated aliphatic hydrocarbon groups, C1-C40 unsaturated aliphatic hydrocarbon groups or aryl groups;

R ¹¹ , R ¹² , R ¹³ , R ¹⁴ , R ¹⁵ , and R ¹⁶ are each independently selected from hydrogen, C1-C40 saturated aliphatic hydrocarbon group, C1-C40 unsaturated aliphatic hydrocarbon group, C6-C14 aryl group, C2-C9 hetero group Aryl or C2-C9 heterocyclic group;

R ¹⁷ is selected from hydrogen, C1-C40 saturated aliphatic hydrocarbon group, C1-C40 unsaturated aliphatic hydrocarbon group, C6-C14 aryl group, C6-C14 arylsulfonyl group, C1-C10 alkylsulfonyl group, C1-C10 acyl group, C2-C9 heteroaryl or C2-C9 heterocyclyl;

R ¹⁸ is selected from hydrogen, C1-C40 saturated aliphatic hydrocarbon group, C1-C40 unsaturated aliphatic hydrocarbon group, C6-C14 aryl group, C6-C14 arylsulfonyl group, C1-C10 alkylsulfonyl group, C1-C10 acyl group or C2-C9 heteroaryl.

It should be noted that R ² , R ³ , R ⁴ , and R ⁵ may be independently selected from the above-mentioned groups, or the adjacent two groups of R ² , R ³ , R ⁴ , and R ⁵ may be the The carbon atoms connecting the two adjacent groups together form a C3-C6 cycloalkyl group or a C2-C9 heterocyclic group, that is, R ² , R ³ , R ⁴ , and R ⁵ only need to satisfy one of the above conditions.

Preferably, X is hydrogen or bromine.

Preferably, R ⁶ is selected from C1-C40 saturated or unsaturated hydrocarbon group, silicon group, C6-C14 aryl group, or C2-C9 heterocyclic group.

More preferably, R ⁶ is selected from a silicon group or a C1-C10 saturated or unsaturated hydrocarbon group, wherein the silicon group includes trimethylsilyl, triisopropylsilyl or methyldi-tert-butylsilyl.

Preferably, the C1-C40 saturated aliphatic hydrocarbon group is selected from C1-C40 alkyl groups.

Preferably, the C1-C40 unsaturated aliphatic hydrocarbon group is selected from C2-C40 alkenyl or C2-C40 alkynyl.

Preferably, the C6-C14 aryl group includes at least one first substituent;

The first substituent is selected from hydrogen, halogen, C1-C40 alkyl, C1-C10 acyl, C1-C40 alkoxy, trifluoromethyl, C6-C14 aryl, C2-C9 heteroaryl, substituted amine group, ester group, cyano group or phosphono group.

More preferably, the first substituent is selected from methyl, methoxy, trifluoromethyl, C6-C14 aryl, C2-C9 heteroaryl, -NR ¹⁵ R ¹⁶ , -CO ₂ R ⁷ , cyano, Halogen, -P(O)(R ¹¹ )(R ¹² ) or -P(O)(OR ¹¹ )(OR ¹² ).

More preferably, the first substituent is selected from halogen, C1-C40 alkyl, C1-C10 acyl or C1-C40 alkoxy.

Preferably, when the C6-C14 aryl group does not contain the first substituent, the C6-C14 aryl group is selected from phenyl or naphthyl.

More preferably, when the C6-C14 aryl group contains the first substituent, the C6-C14 aryl group is selected from phenyl, o-tolyl, o-methoxyphenyl, o-trifluoromethylphenyl, o-arylphenyl, o-heteroarylphenyl, o-substituted aminophenyl, o-ester phenyl, o-cyanophenyl, o-halophenyl, m-tolyl, m-methoxyphenyl, m-substituted aminophenyl, m Trifluoromethylphenyl, m-halophenyl, m-arylphenyl, m-heteroarylphenyl, m-esterylphenyl, m-cyanophenyl, p-tolyl, p-methoxyphenyl, p-substituted amine phenyl, p-trifluoromethylphenyl, p-halophenyl, p-esterylphenyl, p-cyanophenyl, p-arylphenyl and p-heteroarylphenyl, 2,3-bismethoxyphenyl Phenyl, 1-naphthyl, 2-naphthyl or phosphonophenyl.

Preferably, the aryl group, the C2-C9 heteroaryl group and the C2-C9 heterocyclic group all include at least one second substituent;

The second substituent is selected from halogen, C1-C40 alkyl, C1-C10 acyl or C1-C40 alkoxy.

Preferably, the C2-C9 heteroaryl group is selected from furanyl, benzofuranyl, thienyl, benzothienyl, nicotinic acid, isonicotinic acid, pyrrolyl, thiazolyl, oxazolyl, pyrazole group, imidazolyl, pyranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridyl, quinolinyl, isoquinolinyl or carbazolyl.

More preferably, the C2-C9 heteroaryl group is specifically selected from 2-furanyl, 3-furanyl, 2-benzofuranyl, 3-benzofuranyl, 2-thienyl, 3-thienyl, 2-benzene thienyl, 3-benzothienyl, 2-indolyl, 3-indolyl, 2-pyrrolyl, 3-pyrrolyl, 5-thiazolyl, 4-pyrazolyl, 3-pyridyl, 4 -pyridyl, 6-quinolinyl, 5-isoquinolinyl, 2-pyridyl, 2-quinolinyl, 2-pyrazinyl, 2-pyrimidinyl, 1-pyrazolyl or 2-thiazolyl.

Preferably, the C2-C9 heterocyclic group is selected from tetrahydroquinolinyl, N-acyltetrahydroquinolinyl, oxazolinyl, substituted oxazolinyl, tetrahydroindolyl, N-acyltetrahydro Indolyl, dihydropyrrolyl, tetrahydropyridyl, tetrahydrofuranyl, morpholinyl, piperazinyl, piperidinyl, pyrrolinyl or imidazolinyl.

More preferably, the C2-C9 heterocyclic group is selected from 6-tetrahydroquinolinyl, N-acyltetrahydroquinolinyl, 5-tetrahydroindolyl, N-acyltetrahydroindolyl, oxazolinyl , substituted oxazolinyl, tetrahydroquinolinyl, tetrahydroindolyl or 2-oxazolinyl.

Preferably, the molar ratio of the compound of formula (II) to the compound of formula (III) is 1:10-10:1.

More preferably, the molar ratio of the compound of formula (II) to the compound of formula (III) is 1:3 to 1:1.

Preferably, the inert solvent is selected from toluene, tetrahydrofuran, 1,4-dioxane, N,N'-dimethylformamide, N,N'-dimethylacetamide, N-methylpyrrolidone, Dimethyl sulfoxide, 1,2-dichloroethane, diethyl ether, ethylene glycol dimethyl ether, acetonitrile, dichloromethane or acetone;

The oxidizing agent is selected from silver acetate, silver oxide, silver carbonate, silver nitrate, copper acetate, copper sulfate, copper chloride or copper bromide.

The catalyst is selected from the group consisting of dichloro(pentamethylcyclopentadienyl) iridium dimer, dichloro(p-methylcumene) ruthenium dimer, bis(trifluoromethanesulfonyl)imide silver or silver hexafluoroantimonate;

In the present invention, dichloro(pentamethylcyclopentadienyl) iridium dimer, dichloro(p-methylcumene) ruthenium dimer are main catalysts, bis(trifluoromethanesulfonyl)imide Silver amine or silver hexafluoroantimonate is used as a cocatalyst and mainly as a promoter for ligand exchange of the main catalyst.

More preferably, the inert solvent is 1,2-dichloroethane and the oxidant is silver acetate.

Preferably, the dosage of the catalyst is 0.1-20 mol% of the dosage of the compound of formula (II), more preferably 2.5-17.5 mol%.

More preferably, the amount of the main catalyst is 1-5 mol% of the amount of the compound of formula (II), most preferably 2.5 mol%.

Preferably, the reaction temperature is 20-140°C;

The reaction time is 0.1-40h.

More preferably, the reaction temperature is 80-120°C, and the reaction time is 12-24h, most preferably 120°C, 12h.

The present invention also provides the application of the above-mentioned amide compound or the amide compound prepared by the above-mentioned preparation method in pharmaceutical synthesis and/or materials.

To sum up, the present invention has the following advantages:

1. The present invention reacts primary or secondary aromatic amides with alkynyl compounds to obtain primary and secondary amide compounds containing alkynyl groups, and the substrates are simple and easy to obtain;

2. The alkynylation reaction of the direct carbon-hydrogen bonds of ordinary primary and secondary amides without the assistance of an additional guiding group of the present invention avoids tedious steps such as pre-installation and post-reaction removal, easy to operate, economical and environmentally friendly, and has industrial applications value;

3. The dosage of the main catalyst for preparing the amide compound in the present invention is only 1 mol% to 5 mol%, so that the compound has a high synthesis efficiency;

4. The preparation method of the present invention has good chemical selectivity, that is, the preparation method of the present invention uses the strategy of transition metal catalysis to realize the regioselective aryl ortho-carbon-hydrogen bond alkynylation reaction of the amide substrate, and the nitrogen of the amide hydrogen bonds remain unchanged;

5. The preparation method of the present invention has very good regioselectivity, that is, with the assistance of a catalyst and an amide, the reaction is regioselectively reacted on the ortho-position carbon-hydrogen bond of the aromatic ring of the amide, and the traditional electrophilic substitution reaction is not obtained. The mixture of ortho, inter and pair;

6. The scope of application of the substrate of the preparation method of the present invention is very wide, not only the primary and secondary amides can well participate in the synthesis reactions provided in the examples of the present invention, but also the amides substituted by heterocycles can participate in the synthesis provided in the examples of the present invention. reaction, and the pyridine groups with strong coordination such as nicotinamide and isonicotinamide, which are incompatible in previous reports, can also participate in this reaction well;

7. The preparation method of the present invention has good atom economy, and avoids problems such as pre-functionalization of the substrate and removal in the later stage of the reaction;

8. The amide compound of the present invention is a brand-new amide compound, which can be used as a simple organic raw material for synthesizing complex molecules, and is widely used in the fields of medicine and materials.

Description of drawings

In order to explain the embodiments of the present invention or the technical solutions in the prior art more clearly, the following briefly introduces the accompanying drawings that need to be used in the description of the embodiments or the prior art. Obviously, the accompanying drawings in the following description are only These are some embodiments of the present invention. For those of ordinary skill in the art, other drawings can also be obtained based on these drawings without any creative effort.

Fig. 1 is 2-((triisopropylsilyl)acetylene)benzamide (3a) nuclear magnetic resonance ¹ H spectrogram provided in Example 1 of the present invention;

Fig. 2 is the 2-((triisopropylsilyl)acetylene)benzamide (3a) nuclear magnetic resonance ^13C spectrum provided in Example 1 of the present invention;

3 is the nuclear magnetic resonance ¹ H spectrum of 4-acetyl-2-((triisopropylsilyl)acetylene)benzamide (3b) provided in Example 2 of the present invention;

Fig. 4 is the nuclear magnetic resonance ¹³ C spectrum of 4-acetyl-2-((triisopropylsilyl)acetylene)benzamide (3b) provided in Example 2 of the present invention;

Fig. 5 is the nuclear magnetic resonance ¹ H spectrum of 3-((triisopropylsilyl)acetylene)isonicotinamide (3c) provided in Example 3 of the present invention;

Fig. 6 is the nuclear magnetic resonance13C spectrum of ³ -((triisopropylsilyl)acetylene)isonicotinamide (3c) provided in Example 3 of the present invention;

Fig. 7 is the nuclear magnetic resonance ¹ H spectrum of 3-((triisopropylsilyl)acetylene)-2-naphthalenecarboxamide (3d) provided in Example 4 of the present invention;

Fig. 8 is the nuclear magnetic resonance ¹³ C spectrum of 3-((triisopropylsilyl)acetylene)-2-naphthalenecarboxamide (3d) provided in Example 4 of the present invention;

Fig. 9 is the nuclear magnetic resonance ¹ H spectrum of 4-acetamido-2,6-bis((triisopropylsilyl)acetylene)benzamide (3e) provided in Example 5 of the present invention;

Figure 10 is the nuclear magnetic resonance13C spectrum of ⁴ -acetamido-2,6-bis((triisopropylsilyl)acetylene)benzamide (3e) provided in Example 5 of the present invention;

Figure 11 is N-((L)-1-benzyl-1-carboxymethylcarboxylate)-1-(2-((triisopropylsilyl)acetylene)phenyl) provided in Example 6 of the present invention 1H NMR spectrum of methyl- ¹ -amide (3f);

Figure 12 is N-((L)-1-benzyl-1-carboxymethylcarboxylate)-1-(2-((triisopropylsilyl)acetylene)phenyl) provided in Example 6 of the present invention ^13C NMR spectrum of methyl-1-amide (3f);

Figure 13 is the nuclear magnetic resonance ¹ H spectrum of (S)-N-(1-methylethanol)-2-((triisopropylsilyl)acetylene)benzamide (3g) provided in Example 7 of the present invention picture;

Figure 14 is the nuclear magnetic resonance ¹³ C spectrum of (S)-N-(1-methylethanol)-2-((triisopropylsilyl)acetylene)benzamide (3g) provided in Example 7 of the present invention picture.

Detailed ways

The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, other embodiments obtained by persons of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

The amide compounds provided by the present invention and the raw materials and reagents used in the preparation method and application thereof can be purchased from the market.

The amide compound provided by the present invention and its preparation method and application are further described below.

The preparation of embodiment one 2-((triisopropylsilyl)acetylene)benzamide (3a)

Under nitrogen atmosphere, arylsulfonamide compound 1a (12.1 mg, 0.10 mmol), alkynyl bromide or alkyne 2 (20 μL, 0.10 mmol), and dichloro(pentamethylcyclopentadiene) were sequentially added to a 15 mL Schlenk reaction tube. base) iridium dimer (2.3 mg, 0.0025 mmol) or dichloro(p-cymene) ruthenium dimer (1.5 mg, 0.0025 mmol), silver bis(trifluoromethanesulfonyl)imide ( 4.2mg, 0.015mmol) or silver hexafluoroantimonate (5.2mg, 0.015mmol), cesium acetate (30mg, 0.36mmol), (when the reaction uses alkyne bromide, no additional oxidant is needed; when the reaction uses terminal alkyne directly, Then 2 equivalents of silver acetate were needed), 1,2-dichloroethane (DCE, 1 mL), and the reaction was carried out at 120° C. for 12 hours. After the reaction was completed, it was cooled to room temperature, filtered through celite, and concentrated to obtain a crude product. The crude product was separated by chromatography on the prepared silica gel plate, and the selected developing solvent was petroleum ether and ethyl acetate with a volume ratio of 10:1 to obtain the product 2-((triisopropylsilyl)acetylene)benzamide (3a): yellow liquid, yield 93% (27.9 mg).

2-((triisopropylsilyl)acetylene)benzamide (3a) H NMR spectrum measurement results are: ¹ H NMR (400MHz, CDCl ₃ ): δ8.18-8.16(m, 1H), 7.87( brs, 1H), 7.59-7.56 (m, 1H), 7.46-7.43 (m, 2H), 5.84 (brs, 1H), 1.16-1.14 (m, 21H).

2-((Triisopropylsilyl)acetylene)benzamide (3a) The measured results of carbon nuclear magnetic resonance spectrum are: ¹³ C NMR (100MHz, CDCl ₃ ): δ167.9, 134.7, 134.5, 131.4, 130.9, 129.4, 120.6 , 106.1, 99.6, 19.0, 11.6.

Example 2 Preparation of 4-acetyl-2-((triisopropylsilyl)acetylene)benzamide (3b)

Under nitrogen atmosphere, arylamide compound 1b (16.4 mg, 0.10 mmol), alkynyl bromide or alkyne 2 (30 μL, 0.15 mmol), and dichloro(pentamethylcyclopentadienyl) were successively added to a 15 mL Schlenk reaction tube. ) iridium dimer (2.3mg, 0.0025mmol) or dichloro(p-cymene) ruthenium dimer (1.5mg, 0.0025mmol), silver bis(trifluoromethanesulfonyl)imide (4.2 mg, 0.015mmol) or silver hexafluoroantimonate (5.2mg, 0.015mmol), cesium acetate (30mg, 0.36mmol), (when the reaction uses alkyne bromide, no additional oxidant is needed; when the reaction uses terminal alkyne directly, then 2 equivalents of silver acetate were required), 1,2-dichloroethane (DCE, 1 mL), and reacted at 120°C for 12 hours. After the reaction was completed, it was cooled to room temperature, filtered through celite, and concentrated to obtain a crude product. The crude product was separated by chromatography on the prepared silica gel plate, and the selected developing solvent was petroleum ether and ethyl acetate with a volume ratio of 5:1 to obtain the product 4-acetyl-2-((triisopropylsilyl) Acetylene)benzamide (3b): white solid, 76% yield (26.1 mg).

4-Acetyl-2-((triisopropylsilyl)acetylene)benzamide (3b) 1HNMR (400MHz, ^CDCl3 ₎ δ8.24(d, J=8.4Hz) ,1H),8.11(s,1H),7.96(d,J=8.4Hz,1H),7.83(brs,1H),6.20(brs,1H),2.64(s,3H),1.17-1.14(m, 21H).

4-Acetyl-2-((triisopropylsilyl)acetylene)benzamide (3b) The results of carbon nuclear magnetic resonance spectroscopy are: ¹³ CNMR (100MHz, CDCl ₃ )δ195.7,165.9,137.7,136.7,133.0, 130.0, 127.3, 119.9, 103.5, 99.7, 25.8, 17.6, 10.2.

This example is compatible with highly reactive ketone carbonyl groups, and the alkynylation transformation region selectively occurs at the ortho-C-H bond of the arylamide, but not at the ortho-C-H bond of the aryl ketone.

Example three 3-((triisopropylsilyl)acetylene)isonicotinamide (3c)

Under a nitrogen atmosphere, arylamide compound 1c (12.2 mg, 0.10 mmol), alkyne 2 (40 μL, 0.40 mmol), and dichloro(pentamethylcyclopentadienyl)iridium dichloride were successively added to a 15 mL Schlenk tube. polymer (2.3 mg, 0.0025 mmol) or dichloro(p-cymene) ruthenium dimer (1.5 mg, 0.0025 mmol), silver bis(trifluoromethanesulfonyl)imide (4.2 mg, 0.015 mmol) ) or silver hexafluoroantimonate (5.2mg, 0.015mmol), cesium acetate (30mg, 0.36mmol), (when the reaction uses alkyne bromide, no additional oxidant is needed; when the reaction uses terminal alkyne directly, then 2 equivalents of silver acetate), 1,2-dichloroethane (DCE, 1 mL), and reacted at 120° C. for 16 hours. After the reaction was completed, it was cooled to room temperature, and after suction filtration through diatomaceous earth, the crude product obtained by concentrating was subjected to chromatographic separation with a prepared silica gel plate. The product 3-((triisopropylsilyl)acetylene)isonicotinamide (3c) was obtained: yellow solid in 67% yield (20.2 mg).

3-((triisopropylsilyl)acetylene)isonicotinamide (3c) H NMR spectrum measurement results are: ¹ H NMR (400MHz, CDCl ₃ )δ8.82(s,1H),8.68(d,J =4.8Hz,1H), 7.98(d,J=5.2Hz,1H), 7.82(brs,1H), 6.20(brs,1H), 1.15-1.14(m,21H).

3-((triisopropylsilyl)acetylene)isonicotinamide (3c) carbon nuclear magnetic resonance spectrum measurement results are: ¹³ C NMR (100MHz, CDCl ₃ )δ165.6,154.8,149.6,140.6,123.1,116.2,103.2, 102.4, 18.6, 11.2.

In this example, due to the strong coordination ability between the pyridine nitrogen atom and the metal, it is difficult for the previous metal-catalyzed direct carbon-hydrogen bond functionalization reaction to be applied to pyridine derivatives. In this example, it can be directly reacted at the ortho-position carbon-hydrogen bond of isonicotinamide with good medicinal activity, and the direct introduction of an alkynyl group has the potential to obtain a multifunctional pyridine amide derivative through further transformation, which is expected to be used in drug molecules. Find value.

Example 4 3-((triisopropylsilyl)acetylene)-2-naphthalenecarboxamide (3d)

Under a nitrogen atmosphere, arylamide compound 1d (17.1 mg, 0.10 mmol), alkynyl bromide or alkyne 2 (30 μL, 0.15 mmol), dichloro(pentamethylcyclopentadienyl) compound, and dichloro(pentamethylcyclopentadienyl) compound were added to a 15 mL reaction tube. Iridium dimer (2.3mg, 0.0025mmol), or dichloro(p-cymene)ruthenium dimer (1.5mg, 0.0025mmol), silver bis(trifluoromethanesulfonyl)imide (6.0mg , 0.015mmol) or silver hexafluoroantimonate (5.3mg, 0.015mmol), sodium acetate (30mg, 0.36mmol), silver acetate (20mg, 0.12mmol), (when the reaction uses alkyne bromide, no additional oxidant is required; when the reaction When the terminal alkyne is used directly, 2 equivalents of silver acetate are needed), 1,2-dichloroethane (DCE, 1 mL), mixed well, and reacted at 100° C. for 12 hours. After the reaction was completed, it was cooled to room temperature, filtered with vacuum suction, and concentrated to obtain the crude product. The crude product was separated by chromatography on the prepared silica gel plate, and the selected developing solvent was petroleum ether and ethyl acetate with a volume ratio of 20:1 to obtain the product 3-((triisopropylsilyl)acetylene)-2- Naphthalenecarboxamide (3d): yellow solid, 92% yield (30.3 mg).

3-((triisopropylsilyl)acetylene)-2-naphthalenecarboxamide (3d) H NMR spectrum measurement results are: ¹ H NMR (400MHz, CDCl ₃ )δ8.73(s, 1H), 8.10( s,1H),8.04(brs,1H),7.93(d,J=7.6Hz,1H),7.81(d,J=7.6Hz,1H),7.56(t,J=7.4Hz,2H),6.26( brs, 1H), 1.17-1.14 (m, 21H).

3-((triisopropylsilyl)acetylene)-2-naphthalenecarboxamide (3d) carbon nuclear magnetic resonance spectrum measurement results are: ¹³ C NMR (100MHz, CDCl ₃ )δ167.9,135.1,133.8,132.3,132.0,130.3 , 129.2, 128.6, 127.8, 127.1, 116.7, 106.2, 98.0, 18.7, 11.3.

Example five 4-acetamido-2,6-bis((triisopropylsilyl)acetylene)benzamide (3e)

Under nitrogen atmosphere, arylamide compound 1e (17.8 mg, 0.10 mmol), alkynyl bromide or alkyne 2 (60 μL, 0.30 mmol), dichloro(pentamethylcyclopentadienyl) compound was added to a 15 mL reaction tube. Iridium dimer (2.3mg, 0.0025mmol), or dichloro(p-cymene)ruthenium dimer (1.2mg, 0.0020mmol), silver bis(trifluoromethanesulfonyl)imide (4.0mg , 0.010mmol) or silver hexafluoroantimonate (5.3mg, 0.015mmol), sodium acetate (30mg, 0.36mmol), silver acetate (20mg, 0.12mmol), (when the reaction uses alkyne bromide, no additional oxidant is required; when the reaction When the terminal alkyne is used directly, 2 equivalents of silver acetate are needed), 1,2-dichloroethane (DCE, 1 mL), mixed well, and reacted at 80°C for 12 hours. After the reaction was completed, it was cooled to room temperature, filtered with vacuum suction, and concentrated to obtain the crude product. The crude product is separated by chromatography on the prepared silica gel plate, and the selected developing solvent is that the volume ratio of petroleum ether and ethyl acetate is 3:1, and the product 4-acetamido-2,6-bis((triisopropyl) is obtained. Silyl)acetylene)benzamide (3e): yellow liquid, 58% yield (31.2 mg).

4-Acetylamino-2,6-bis((triisopropylsilyl)acetylene)benzamide (3e) H NMR spectrum measurement results are: ¹ H NMR (400MHz, CDCl ₃ )δ8.68(s, 1H), 8.29(s, 1H), 8.12(brs, 1H), 7.96(brs, 1H), 5.78(brs, 1H), 2.21(s, 3H), 1.17-1.13(m, 42H).

4-Acetylamino-2,6-bis((triisopropylsilyl)acetylene)benzamide (3e) was determined by carbon nuclear magnetic resonance spectrum: ¹³ C NMR (100MHz, CDCl ₃ )δ168.7,166.7,141.5, 134.8, 128.9, 123.8, 105.9, 102.0, 101.8, 101.0, 25.1, 19.1, 19.0, 11.6, 11.5.

This example is compatible with highly reactive acetamido groups, and the alkynylation conversion region selectively occurs at the ortho-position C-H bond of the aryl amide instead of the ortho-position C-H bond of the aryl acetamido group. This further proves that the coordinating ability of the primary amide-directing group is stronger than that of the acetamido group, and also illustrates the good regioselectivity of the transformation, which also provides a basis for the selective late-stage derivatization of amino-substituted benzamide-based bioactive molecules. new strategy.

Example 6 N-((L)-1-benzyl-1-carboxymethyl-1-carboxylate)-1-(2-((triisopropylsilyl)acetylene)phenyl)methyl-1-amide (3f )

Under nitrogen atmosphere, arylamide compound 1e (28.3 mg, 0.10 mmol), alkynyl bromide or terminal alkyne 2 (30 μL, 0.15 mmol), dichloro (pentamethylcyclopentadienyl) was added to a 15 mL reaction tube iridium dimer (2.3mg, 0.0025mmol) or dichloro(p-cymene)ruthenium dimer (1.5mg, 0.0025mmol), silver bis(trifluoromethanesulfonyl)imide (4.2mg , 0.015mmol) or silver hexafluoroantimonate (5.2mg, 0.015mmol), cesium acetate (30mg, 0.36mmol), (when the reaction uses alkyne bromide, no additional oxidant is needed; when the reaction uses terminal alkyne directly, then it is required 2 equiv of silver acetate), 1,2-dichloroethane (DCE, 1 mL), and reacted at 120°C for 12 hours. After the reaction was completed, it was cooled to room temperature, filtered through celite, and concentrated to obtain a crude product. The crude product was separated by chromatography on the prepared silica gel plate, and the selected developing solvent was petroleum ether and ethyl acetate in a volume ratio of 10:1 to obtain the product N-((L)-1-benzyl-1-carboxylic acid methyl ester Ester)-1-(2-((triisopropylsilyl)acetylene)phenyl)methyl-1-amide (3f): white solid, 78% yield (36.1 mg).

N-((L)-1-Benzyl-1-carboxymethylcarboxylate)-1-(2-((triisopropylsilyl)acetylene)phenyl)methyl-1-amide (3f) NMR The measurement results of hydrogen spectrum are: ¹ H NMR (400MHz, CDCl ₃ )δ7.90-7.85(m, 1H), 7.70(d, J=7.2Hz, 1H), 7.58-7.55(m, 1H), 7.39(t , J=7.2Hz, 3.6Hz 2H), 7.25–7.21(m, 2H), 7.18(d, J=7.2Hz, 2H), 5.02(q, J=6.8Hz, 1H), 3.68(s, 3H) , 3.29 (dd, J=14.0, 6.8Hz, 1H), 3.20 (dd, J=13.6, 6.4Hz, 1H), 1.15-1.13 (m, 21H).

N-((L)-1-Benzyl-1-carboxymethylcarboxylate)-1-(2-((triisopropylsilyl)acetylene)phenyl)methyl-1-amide (3f) NMR The results of carbon spectrometry were: ¹³ C NMR (100 MHz, CDCl ₃ ) δ 134.8, 130.5, 129.3, 128.7, 128.5, 127.0, 54.5, 38.13 18.70, 11.3.

This example can be compatible with arylamides derived from chiral amino acid esters, and obtain alkynylated products with retained chirality. In view of the high activity of alkynyl groups, for example, high functional groups can be obtained through electrophilic and nucleophilic addition reactions. , making this transformation highly practical.

Example seven (s)-N-(1-methylethanol)-2-((triisopropylsilyl)acetylene)benzamide (3g)

Under a nitrogen atmosphere, 1 g (17.9 mg, 0.10 mmol) of arylamide compound, 2 (30 μL, 0.15 mmol) of alkynyl bromide, 2 (30 μL, 0.15 mmol) of arylamide compound, dichloro(pentamethylcyclopentadienyl) were added to a 15 mL reaction tube. ) iridium dimer (2.3mg, 0.0025mmol) or dichloro(p-cymene) ruthenium dimer (1.5mg, 0.0025mmol), silver bis(trifluoromethanesulfonyl)imide (4.2 mg, 0.015mmol) or silver hexafluoroantimonate (5.2mg, 0.015mmol), cesium acetate (30mg, 0.36mmol), (when the reaction uses alkyne bromide, no additional oxidant is needed; when the reaction uses terminal alkyne directly, then 2 equivalents of silver acetate were required), 1,2-dichloroethane (DCE, 1 mL), and reacted at 120°C for 12 hours. After the reaction was completed, it was cooled to room temperature, filtered through celite, and concentrated to obtain a crude product. The crude product is separated by chromatography on the prepared silica gel plate, and the selected developing agent or eluent is petroleum ether and the volume ratio of ethyl acetate is 5:1 to obtain the product (S)-N-(1-methylethanol) )-2-((triisopropylsilyl)acetylene)benzamide (3 g): white solid, 82% yield (29.4 mg).

(S)-N-(1-methylethanol)-2-((triisopropylsilyl)acetylene)benzamide (3g) ^1H NMR (400MHz, _CDCl3 ) δ8.14(brs,1H),8.09(t,J=4.8Hz,1H),7.57-7.55(m,1H),7.42(t,J=4.4Hz,2H),4.05-4.01(m,1H) , 3.59-3.53 (m, 1H), 3.43-3.36 (m, 1H), 1.21 (d, J=6.4Hz, 2H), 1.14-1.13 (m, 21H).

(S)-N-(1-methylethanol)-2-((triisopropylsilyl)acetylene)benzamide (3g) The results of carbon nuclear magnetic resonance spectroscopy are: ¹³ C NMR (100MHz, CDCl ₃ ) δ167.6, 134.6, 134.5, 130.7, 130.2, 129.0, 119.8, 105.5, 99.1, 67.9, 48.2, 20.9, 18.7, 11.2.

In addition to being compatible with the above-mentioned chiral amino acid ester-derived aryl amides to obtain chirality-retained alkynylation products, this example is also compatible with biologically active amino alcohol-derived amides.

It can be seen from the above examples that the substrates in the embodiments of the present invention are simple and easy to obtain, have few synthesis steps, are economical and environmentally friendly, and can simply and efficiently prepare amide compounds.

As mentioned above, the above embodiments are only used to illustrate the technical solutions of the present invention, but not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand: The technical solutions described in the embodiments are modified, or some technical features thereof are equivalently replaced; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the spirit and scope of the technical solutions in the embodiments of the present invention.

Claims (4)

1. the preparation method of the amide compound of a structure as shown in formula (I), is characterized in that, comprises the following steps: In the presence of an inert solvent, under the action of a catalyst, an oxidant and cesium acetate, the compound of formula (II) is reacted with the compound of formula (III) to obtain the compound of formula (I);

Wherein, X is hydrogen, in formula (I)

Represents a C6-C14 aryl group or a C4-C8 heteroaryl group containing S and O; R ¹ is hydrogen; R ² , R ³ , R ⁴ and R ⁵ are each independently selected from hydrogen, C1-C40 saturated aliphatic hydrocarbon group, C1-C40 unsaturated aliphatic hydrocarbon group, C1-C40 alkoxy group, C1-C40 alkylthio group, halogenated C1-C40 saturated aliphatic hydrocarbon group, halogenated C1-C40 unsaturated aliphatic hydrocarbon group, halogenated C1-C40 alkoxy group, halogen, nitro, cyano, -NR ¹⁵ R ¹⁶ , C6-C14 aryl group , substituted C6-C14 aryl, C6-C14 aryloxy, C2-C9 heteroaryl, substituted C2-C9 heteroaryl, C2-C9 heterocyclyl or substituted C2-C9 heterocyclyl; R ⁶ is a silicon base; R ¹⁵ and R ¹⁶ are each independently selected from hydrogen, C1-C40 saturated aliphatic hydrocarbon group, C1-C40 unsaturated aliphatic hydrocarbon group, C6-C14 aryl group, substituted C6-C14 aryl group, C2-C9 heteroaryl group, substituted C2 ~C9 heteroaryl, C2~C9 heterocyclyl or substituted C2~C9 heterocyclyl; The substituted C6-C14 aryl group refers to being substituted by at least one first substituent; The first substituent is selected from halogen, C1-C40 alkyl, C1-C10 acyl, C1-C40 alkoxy, trifluoromethyl, C6-C14 aryl, C2-C9 heteroaryl, -NR ¹⁵ R ¹⁶ , -CO ₂ R ⁷ , cyano, -P(O)(R ¹¹ )(R ¹² ) or -P(O)(OR ¹¹ )(OR ¹² ); R ⁷ is each selected from hydrogen, C1-C40 saturated aliphatic hydrocarbon group, C1-C40 unsaturated aliphatic hydrocarbon group, aryl group or substituted aryl group; R ¹¹ , R ¹² , R ¹⁵ and R ¹⁶ are each independently selected from hydrogen, C1-C40 saturated aliphatic hydrocarbon group, C1-C40 unsaturated aliphatic hydrocarbon group, C6-C14 aryl group, C2-C9 heteroaryl group or C2-C9 Heterocyclyl; The substituted aryl group, the substituted C2-C9 heteroaryl group and the substituted C2-C9 heterocyclic group refer to being substituted by at least one second substituent; The second substituent is selected from halogen, C1-C40 alkyl, C1-C10 acyl or C1-C40 alkoxy; Described oxidizing agent is selected from silver acetate, silver oxide, silver carbonate or silver nitrate; The catalyst is selected from one of dichloro(pentamethylcyclopentadienyl) iridium dimer and dichloro(p-methylcumene) ruthenium dimer, and bis(trifluoromethanesulfonyl) ) one of silver imide and silver hexafluoroantimonate; The inert solvent is selected from tetrahydrofuran, 1,4-dioxane, N,N'-dimethylformamide, N,N'-dimethylacetamide, N-methylpyrrolidone, dimethylsulfoxide, 1,2-Dichloroethane, diethyl ether, ethylene glycol dimethyl ether, acetonitrile, dichloromethane or acetone. 2 . The preparation method according to claim 1 , wherein the molar ratio of the compound of formula (II) to the compound of formula (III) is 1:10-10:1. 3 . 3 . The preparation method according to claim 1 , wherein the amount of the catalyst used is 0.1-20 mol % of the amount of the compound of formula (II). 4 . 4. preparation method according to claim 1, is characterized in that, described reaction temperature is 20～140 ℃; The reaction time is 0.1-40h.

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