CN107915653A - Catalysis ester and amine carry out the method that reaction prepares acid amides - Google Patents

Catalysis ester and amine carry out the method that reaction prepares acid amides Download PDF

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CN107915653A
CN107915653A CN201711261653.5A CN201711261653A CN107915653A CN 107915653 A CN107915653 A CN 107915653A CN 201711261653 A CN201711261653 A CN 201711261653A CN 107915653 A CN107915653 A CN 107915653A
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reaction
alkyl
amine
atom
acid amides
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CN107915653B (en
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姚英明
黎兆
袁丹
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Suzhou University
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Suzhou University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C231/00—Preparation of carboxylic acid amides
    • C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B43/00—Formation or introduction of functional groups containing nitrogen
    • C07B43/06—Formation or introduction of functional groups containing nitrogen of amide groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/36—Radicals substituted by singly-bound nitrogen atoms
    • C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides
    • C07D213/82—Amides; Imides in position 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
    • C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
    • C07D295/182—Radicals derived from carboxylic acids
    • C07D295/192—Radicals derived from carboxylic acids from aromatic carboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D307/10—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D307/14—Radicals substituted by nitrogen atoms not forming part of a nitro radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D307/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen

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Abstract

The present invention provides a kind of method for being catalyzed ester and amine reaction synthesizing amide, and the raw material of this method is simple and easy to get, easy to operate, and without adding solvent, yield is higher, and the substrate scope of application is wider.Comprise the following steps：The ester of formula (I) and the amine of formula (II) react under catalysis of the alkoxy rare-earth metal cluster compound for containing alkali metallic sodium as catalyst, obtain the compound of formula (III)；Or the ester of formula (I) and the amine of formula (IV) react under catalysis of the alkoxy rare-earth metal cluster compound for containing alkali metallic sodium as catalyst, obtain the compound of formula (V), wherein R1Selected from alkyl, aryl or heteroaryl；R2、R3、R4Independently selected from alkylol, alkyl, cycloalkyl, heterocyclic radical, aromatic radical or heteroaryl, or R3、R4Independently selected from alkylol, alkyl and R3、R4Atom connected to them forms ring.Its reaction equation difference is as follows：

Description

Catalysis ester and amine carry out the method that reaction prepares acid amides
Technical field
The present invention relates to organic chemistry filed, more particularly to a kind of catalysis ester and amine to carry out the method that reaction prepares acid amides.
Background technology
Amide groups is a kind of functional group with significant application value, is widely present in polymer, natural products and medicine In thing.Acid amides is also used as ligand and metal complex, plays the role of stable metal center, and the diversity of its structure is also The diversity of metal complex and catalyst provides basis.Therefore, exploitation efficiently prepares the method for acid amides not only with important Theory significance, is always the hot spot of research also with potential application value.
Ester and amine reaction generation acid amides under catalytic condition, accessory substance is alcohol, avoids the acyl used in conventional synthesis process The alkali of the reagents such as halogen, acid anhydrides and equivalent, meets the requirement of Green Chemistry, is to prepare the safer efficient side of amide-type product Method.The larger amount of inorganic base of known method generally use or organic base promote the progress of this kind of reaction, the reaction time compared with Long, substrate limitation is larger.Therefore, simple and easy to get and efficient catalyst is developed, to be catalyzed the progress of ester and amine reaction, tool There is important meaning.
The content of the invention
In order to solve the above technical problems, the object of the present invention is to provide a kind of side for being catalyzed ester and amine reaction synthesizing amide Method.The raw material of this method is simple and easy to get, easy to operate, and without adding solvent, yield is higher, and the substrate scope of application is wider.
React the method for preparing acid amides the present invention provides a kind of catalysis ester and amine, comprises the following steps：
The ester of formula (I) and the amine of formula (II) are containing the alkoxy rare-earth metal cluster compound of alkali metallic sodium as catalyst Under catalysis, react under certain reaction temperature, obtain the compound of formula (III)；Or the ester of formula (I) and the amine of formula (IV) In the case where containing catalysis of the alkoxy rare-earth metal cluster compound of alkali metallic sodium as catalyst, occur under certain reaction temperature Reaction, obtains the compound of formula (V)；Its reaction equation difference is as follows：
Wherein, R1Selected from alkyl, aryl or heteroaryl；
R2、R3、R4Independently select alkylol, alkyl, cycloalkyl, heterocyclic radical, aromatic radical or heteroaryl；
Or
R3、R4Independently selected from alkylol, alkyl and R3、R4Atom connected to them forms ring；
Further, the alkyl is saturated alkyl or unsaturated alkyl containing 1-14 atom；The unsaturation alkane Base includes alkenyl or alkynyl.
Preferably, the alkyl is saturated alkyl or unsaturated alkyl containing 1-6 atom；The unsaturated alkyl bag Include alkenyl or alkynyl.
It is highly preferred that the saturated alkyl includes methyl, ethyl, propyl group, butyl, amyl group or hexyl.
It is highly preferred that the unsaturated alkyl include vinyl, acrylic, cyclobutenyl, pentenyl, hexenyl, acetenyl, Propinyl, butynyl, pentynyl or hexin base.
Further, the alkylol is primary alconol or secondary alcohol containing 1-6 carbon atom.
Further, the alkylol is the primary alconol containing 1-6 carbon atom.
Preferably, the alkylol is-CH2OH ,-CH2CH2OH ,-CH2CH2CH2OH ,-CH2CH2CH2CH2OH ,- CH2CH2CH2CH2CH2OH ,-CH2CH2CH2CH2CH2CH2OH。
Further, the cycloalkyl is saturation or unsaturation ring containing 1-14 atom；The heterocyclic radical be with Nitrogen, the saturation containing 1-14 atom of oxygen or sulfur heteroatom or undersaturated ring.
Yet further, the cycloalkyl is the full or undersaturated ring containing 1-6 atom；The heterocyclic radical be with Nitrogen, the saturation containing 1-6 atom of oxygen or sulfur heteroatom or undersaturated ring.
Preferably, the cycloalkyl includes cyclohexyl, cyclopenta, cyclopropyl；The heterocyclic radical includes tetrahydrofuran base, pyrrole Piperidinyl, piperidyl, pyrrole radicals, furyl.
Further, when the alkyl and cycloalkyl are substituted with a substituent, the substituent may be selected from hydroxyl, phenyl Or benzyl.
Preferably, the alkyl group being substituted with a substituent includes benzyl, styryl, phenethyl.
Further, the aryl is the aryl containing 5-14 atom；The heteroaryl is former with nitrogen, oxygen or thia The aryl containing 5-14 atom of son.
Preferably, the aryl is the aryl containing 5-10 atom；The heteroaryl is with nitrogen or oxygen heteroatom Aryl containing 5-10 atom.
It is highly preferred that the aryl includes phenyl, pyridine radicals, furyl.
Further, when the aryl and heteroaryl are substituted with a substituent, the substituent may be selected from alkyl, halogen Element, trifluoromethyl；The halogen is fluorine, chlorine, bromine and iodine.
Further, R3、R4Independently selected from alkylol, alkyl and R3、R4Atom connected to them forms ring.
Yet further, R3、R4Independently selected from alkylol, alkyl and R3、R4Atom connected to them, which is formed, to be contained The cycloalkyl of 4-14 atom contains oxa alkyl containing 4-14 atom.
Further, R3、R4Independently selected from alkylol, alkyl and R3、R4Atom connected to them, which is formed, to be contained The cycloalkyl of 4-10 atom contains oxa alkyl containing 4-10 atom.
Further, the ester of formula (I) for methyl benzoate, methyl p-methyl benzoate, parabromobenzoic acid methyl esters, to trifluoro Methyl toluate, methyl cinnamate, iso methyl nicotinate, methylfuroate, methyl phenylacetate.
Further, the amine of formula (II) or formula (IV) for benzylamine, nafoxidine, morpholine, 3- pyridyl-methanamines, 2- phenyl ethylamines, N-butylamine, 2- tetrahydrofurfuryl amines, monoethanolamine, N- methylbenzylamines.
Preferably, ester is methyl benzoate, and amine is benzylamine.
Further, the alkoxy rare-earth metal cluster compound containing alkali metallic sodium is Nd2Na8(OCH2CH2NMe2)12(OH)2、 Y2Na8(OCH2CF3)14(THF)6、Nd2Na8(OCH2CF3)14(THF)6Or La2Na8(OCH2CF3)14(THF)6。
Preferably, the alkoxy rare-earth metal cluster compound containing alkali metallic sodium is La2Na8(OCH2CF3)14(THF)6。
Yet further, the reaction is 40-80 DEG C.
Further, when the reaction time is 3-12 small.
Further, the molar ratio of ester, fatty amine and rare earth metal cluster compound is 1:1-1.2:0.0025-0.01.
Preferably, the molar ratio of methyl benzoate, benzylamine and rare earth metal cluster compound is 1:1.2:0.005, at 40-80 DEG C Lower reaction 6h.
Preferably, it is 1 by the molar ratio of methyl benzoate, benzylamine and rare earth metal cluster compound:1.2:0.005, at 80 DEG C Lower reaction 6h.
Further, above reaction carries out in anhydrous conditions.
Further, react in the progress under confined conditions containing protective atmosphere.
Further, protective atmosphere is argon gas atmosphere or nitrogen atmosphere.
Further, reaction need not add solvent.
Further, after reaction, the step of being isolated and purified to product is further included.
Further, isolation and purification method is column chromatography and/or thin-layer chromatography.
The reaction principle of the present invention is as follows：In La2Na8(OCH2CF3)14(THF)6In the presence of A, substrate ester and amine are activated Form intermediate B.The ester being activated is reacted with the amine for sloughing Hydrogen Proton with the pattern shown by intermediate C, generates product Acid amides, while the alcohol of a molecule is sloughed, and regenerated catalyst A, it is achieved thereby that catalytic cycle.The route map of concrete principle As shown in Fig. 2.
According to the above aspect of the present invention, the present invention has at least the following advantages：
The present invention utilizes catalyst La2Na8(OCH2CF3)14(THF)6A is catalyzed the reaction of ester and fatty amine, used catalyst Easily prepared, reaction raw materials are simple and easy to get, and operation is easy, and yield is higher, and the substrate scope of application is wider.
Described above is only the general introduction of technical solution of the present invention, in order to better understand the technological means of the present invention, And can be practiced according to the content of specification, below with presently preferred embodiments of the present invention and coordinate attached drawing describe in detail as after.
Brief description of the drawings
Fig. 1 is the nucleus magnetic hydrogen spectrum for the acid amides that the embodiment of the present invention 1 synthesizes.
Fig. 2 is reaction principle route map of the present invention.
Embodiment
With reference to the accompanying drawings and examples, the embodiment of the present invention is described in further detail.Implement below Example is used to illustrate the present invention, but is not limited to the scope of the present invention.
Embodiment 1
Present embodiments provide one kind and utilize 1mol%Nd2Na8(OCH2CH2NMe2)12(OH)2Benzene is catalyzed under the conditions of 80 DEG C The method of the reaction of methyl formate and benzylamine, comprises the following steps that：
Weigh the Nd of 15.7mg (0.01mmol)2Na8(OCH2CH2NMe2)12(OH)2In the reaction bulb with stirrer, 125 μ L (1.0mmol) methyl benzoates and 131 μ L (1.2mmol) benzylamines are added into the reaction bulb, in anhydrous, anaerobic and are adopted Under conditions of being protected with argon gas, 12h is reacted under the conditions of 80 DEG C.After reaction, through column chromatography (ethyl acetate/petroleum ether=1/ 4) target product 113mg, yield 54%, are obtained.The structural formula of target product is as follows：
Embodiment 2
Present embodiments provide one kind and utilize 1mol%Y2Na8(OCH2CF3)14(THF)6Benzene first is catalyzed under the conditions of 80 DEG C The method of the reaction of sour methyl esters and benzylamine, comprises the following steps that：
Weigh the Y of 21.8mg (0.01mmol)2Na8(OCH2CF3)14(THF)6In the reaction bulb with stirrer, to this 125 μ L (1.0mmol) methyl benzoates and 131 μ L (1.2mmol) benzylamines are added in reaction bulb, in anhydrous, anaerobic and use argon Under conditions of gas shielded, 12h is reacted under the conditions of 80 DEG C.After reaction, through column chromatography (ethyl acetate/petroleum ether=1/4), obtain To target product 42mg, yield 20%.The structural formula of target product is as follows：
Embodiment 3
Present embodiments provide one kind and utilize 1mol%Nd2Na8(OCH2CF3)14(THF)6Benzene first is catalyzed under the conditions of 80 DEG C The method of the reaction of sour methyl esters and benzylamine, comprises the following steps that：
Weigh the Nd of 22.9mg (0.01mmol)2Na8(OCH2CF3)14(THF)6In the reaction bulb with stirrer, to 125 μ L (1.0mmol) methyl benzoates and 131 μ L (1.2mmol) benzylamines are added in the reaction bulb, in anhydrous, anaerobic and are used Under conditions of argon gas protection, 12h is reacted under the conditions of 80 DEG C.After reaction, through column chromatography (ethyl acetate/petroleum ether=1/ 4) target product 158mg, yield 75%, are obtained.The structural formula of target product is as follows：
Embodiment 4
Present embodiments provide one kind and utilize 0.5mol%La2Na8(OCH2CF3)14(THF)6Benzene is catalyzed under the conditions of 80 DEG C The method of the reaction of methyl formate and benzylamine, comprises the following steps that：
Weigh the La of 11.4mg (0.005mmol)2Na8(OCH2CF3)14(THF)6In the reaction bulb with stirrer, to 125 μ L (1.0mmol) methyl benzoates and 131 μ L (1.2mmol) benzylamines are added in the reaction bulb, in anhydrous, anaerobic and are used Under conditions of argon gas protection, 6h is reacted under the conditions of 80 DEG C.After reaction, through column chromatography (ethyl acetate/petroleum ether=1/4), Obtain target product 198mg, yield 94%.The structural formula of target product is as follows：
Embodiment 5
Present embodiments provide one kind and utilize 0.5mol%La2Na8(OCH2CF3)14(THF)6The catalysis pair under the conditions of 80 DEG C The method of the reaction of methyl toluate and benzylamine, comprises the following steps that：
Weigh the La of 11.4mg (0.005mmol)2Na8(OCH2CF3)14(THF)6In the reaction bulb with stirrer, to 142 μ L (1.0mmol) methyl p-methyl benzoates and 131 μ L (1.2mmol) benzylamines are added in the reaction bulb, in anhydrous, anaerobic And under conditions of being protected using argon gas, react 6h under the conditions of 80 DEG C.After reaction, through column chromatography (ethyl acetate/petroleum ether =1/4) target product 192mg, yield 85%, are obtained.The structural formula of target product is as follows：
Embodiment 6
Present embodiments provide one kind and utilize 0.5mol%La2Na8(OCH2CF3)14(THF)6The catalysis pair under the conditions of 80 DEG C The method of the reaction of methyl-bromobenzoate and benzylamine, comprises the following steps that：
Weigh the La of 11.4mg (0.005mmol)2Na8(OCH2CF3)14(THF)6In the reaction bulb with stirrer, to 215mg (1.0mmol) parabromobenzoic acid methyl esters and 131 μ L (1.2mmol) benzylamines are added in the reaction bulb, in anhydrous, anaerobic And under conditions of being protected using argon gas, react 6h under the conditions of 80 DEG C.After reaction, through column chromatography (ethyl acetate/petroleum ether =1/4) target product 275mg, yield 95%, are obtained.The structural formula of target product is as follows：
Embodiment 7
Present embodiments provide one kind and utilize 0.5mol%La2Na8(OCH2CF3)14(THF)6The catalysis pair under the conditions of 80 DEG C The method of the reaction of methyl-bromobenzoate and benzylamine, comprises the following steps that：
Weigh the La of 11.4mg (0.005mmol)2Na8(OCH2CF3)14(THF)6In the reaction bulb with stirrer, to 161 μ L (1.0mmol) are added in the reaction bulb to trifluoromethyl benzoic acid methyl ester and 131 μ L (1.2mmol) benzylamines, it is anhydrous, Under conditions of anaerobic and use argon gas protection, 6h is reacted under the conditions of 80 DEG C.After reaction, through column chromatography (ethyl acetate/oil Ether=1/1), obtain target product 276mg, yield 99%.The structural formula of target product is as follows：
Embodiment 8
Present embodiments provide one kind and utilize 0.5mol%La2Na8(OCH2CF3)14(THF)6The catalysis pair under the conditions of 80 DEG C The method of the reaction of methyl-bromobenzoate and benzylamine, comprises the following steps that：
Weigh the La of 11.4mg (0.005mmol)2Na8(OCH2CF3)14(THF)6In the reaction bulb with stirrer, to 162mg (1.0mmol) methyl cinnamates and 131 μ L (1.2mmol) benzylamines are added in the reaction bulb, in anhydrous, anaerobic and are adopted Under conditions of being protected with argon gas, 6h is reacted under the conditions of 80 DEG C.After reaction, through column chromatography (ethyl acetate/petroleum ether=1/ 4) target product 197mg, yield 83%, are obtained.The structural formula of target product is as follows：
Embodiment 9
Present embodiments provide one kind and utilize 0.5mol%La2Na8(OCH2CF3)14(THF)6It is catalyzed under the conditions of 80 DEG C different The method of the reaction of methyl nicotinate and benzylamine, comprises the following steps that：
Weigh the La of 11.4mg (0.005mmol)2Na8(OCH2CF3)14(THF)6In the reaction bulb with stirrer, to 118 μ L (1.0mmol) iso methyl nicotinates and 131 μ L (1.2mmol) benzylamines are added in the reaction bulb, in anhydrous, anaerobic and are used Under conditions of argon gas protection, 6h is reacted under the conditions of 80 DEG C.After reaction, through column chromatography (ethyl acetate/petroleum ether=1/2), Obtain target product 204mg, yield 96%.The structural formula of target product is as follows：
Embodiment 10
Present embodiments provide one kind and utilize 0.5mol%La2Na8(OCH2CF3)14(THF)6Chaff is catalyzed under the conditions of 80 DEG C The method of the reaction of sour methyl esters and benzylamine, comprises the following steps that：
Weigh the La of 11.4mg (0.005mmol)2Na8(OCH2CF3)14(THF)6In the reaction bulb with stirrer, to 107 μ L (1.0mmol) methylfuroates and 131 μ L (1.2mmol) benzylamines are added in the reaction bulb, in anhydrous, anaerobic and use argon Under conditions of gas shielded, 6h is reacted under the conditions of 80 DEG C.After reaction, through column chromatography (ethyl acetate/petroleum ether=1/4), obtain To target product 199mg, yield 99%.The structural formula of target product is as follows：
Embodiment 11
Present embodiments provide one kind and utilize 0.5mol%La2Na8(OCH2CF3)14(THF)6Benzene is catalyzed under the conditions of 80 DEG C The method of the reaction of methyl acetate and benzylamine, comprises the following steps that：
Weigh the La of 11.4mg (0.005mmol)2Na8(OCH2CF3)14(THF)6In the reaction bulb with stirrer, to 141 μ L (1.0mmol) methyl phenylacetates and 131 μ L (1.2mmol) benzylamines are added in the reaction bulb, in anhydrous, anaerobic and are used Under conditions of argon gas protection, 6h is reacted under the conditions of 80 DEG C.After reaction, through column chromatography (ethyl acetate/petroleum ether=1/2), Obtain target product 223mg, yield 99%.The structural formula of target product is as follows：
Embodiment 12
Present embodiments provide one kind and utilize 0.5mol%La2Na8(OCH2CF3)14(THF)6Benzene is catalyzed under the conditions of 80 DEG C The method of the reaction of methyl acetate and 3- pyridyl-methanamines, comprises the following steps that：
Weigh the La of 11.4mg (0.005mmol)2Na8(OCH2CF3)14(THF)6In the reaction bulb with stirrer, to 125 μ L (1.0mmol) methyl benzoates and 123 μ L (1.2mmol) 3- pyridyl-methanamines are added in the reaction bulb, in anhydrous, anaerobic And under conditions of being protected using argon gas, react 6h under the conditions of 80 DEG C.After reaction, through column chromatography (ethyl acetate/petroleum ether =1/4) target product 197mg, yield 93%, are obtained.The structural formula of target product is as follows：
Embodiment 13
Present embodiments provide one kind and utilize 0.5mol%La2Na8(OCH2CF3)14(THF)6Benzene is catalyzed under the conditions of 80 DEG C The method of the reaction of methyl acetate and 2- phenyl ethylamines, comprises the following steps that：
Weigh the La of 11.4mg (0.005mmol)2Na8(OCH2CF3)14(THF)6In the reaction bulb with stirrer, to 125 μ L (1.0mmol) methyl benzoates and 151 μ L (1.2mmol) 2- phenyl ethylamines are added in the reaction bulb, in anhydrous, anaerobic simultaneously Under conditions of being protected using argon gas, 6h is reacted under the conditions of 80 DEG C.After reaction, through column chromatography (ethyl acetate/petroleum ether=1/ 4) target product 223mg, yield 99%, are obtained.The structural formula of target product is as follows：
Embodiment 14
Present embodiments provide one kind and utilize 0.5mol%La2Na8(OCH2CF3)14(THF)6Benzene is catalyzed under the conditions of 80 DEG C The method of the reaction of methyl acetate and n-butylamine, comprises the following steps that：
Weigh the La of 11.4mg (0.005mmol)2Na8(OCH2CF3)14(THF)6In the reaction bulb with stirrer, to 125 μ L (1.0mmol) methyl benzoates and 119 μ L (1.2mmol) n-butylamines are added in the reaction bulb, in anhydrous, anaerobic and are adopted Under conditions of being protected with argon gas, 6h is reacted under the conditions of 80 DEG C.After reaction, through column chromatography (ethyl acetate/petroleum ether=1/ 4) target product 170mg, yield 96%, are obtained.The structural formula of target product is as follows：
Embodiment 15
Present embodiments provide one kind and utilize 0.5mol%La2Na8(OCH2CF3)14(THF)6Benzene is catalyzed under the conditions of 80 DEG C The method of the reaction of methyl acetate and nafoxidine, comprises the following steps that：
Weigh the La of 11.4mg (0.005mmol)2Na8(OCH2CF3)14(THF)6In the reaction bulb with stirrer, to 125 μ L (1.0mmol) methyl benzoates and 99 μ L (1.2mmol) nafoxidines are added in the reaction bulb, in anhydrous, anaerobic simultaneously Under conditions of being protected using argon gas, 6h is reacted under the conditions of 80 DEG C.After reaction, through column chromatography (ethyl acetate/petroleum ether=1/ 4) target product 174mg, yield 99%, are obtained.The structural formula of target product is as follows：
Embodiment 16
Present embodiments provide one kind and utilize 0.5mol%La2Na8(OCH2CF3)14(THF)6Benzene is catalyzed under the conditions of 80 DEG C The method of the reaction of methyl acetate and morpholine, comprises the following steps that：
Weigh the La of 11.4mg (0.005mmol)2Na8(OCH2CF3)14(THF)6In the reaction bulb with stirrer, to 125 μ L (1.0mmol) methyl benzoates and 105 μ L (1.2mmol) morpholines are added in the reaction bulb, in anhydrous, anaerobic and are used Under conditions of argon gas protection, 6h is reacted under the conditions of 80 DEG C.After reaction, through column chromatography (ethyl acetate/petroleum ether=1/4), Obtain target product 189mg, yield 99%.The structural formula of target product is as follows：
Embodiment 17
Present embodiments provide one kind and utilize 0.5mol%La2Na8(OCH2CF3)14(THF)6Benzene is catalyzed under the conditions of 80 DEG C The method of the reaction of methyl acetate and 2- tetrahydrofurfuryl amines, comprises the following steps that：
Weigh the La of 11.4mg (0.005mmol)2Na8(OCH2CF3)14(THF)6In the reaction bulb with stirrer, to 125 μ L (1.0mmol) methyl benzoates and 124 μ L (1.2mmol) 2- tetrahydrofurfuryl amines are added in the reaction bulb, in anhydrous, anaerobic And under conditions of being protected using argon gas, react 6h under the conditions of 80 DEG C.After reaction, through column chromatography (ethyl acetate/petroleum ether =1/4) target product 201mg, yield 98%, are obtained.The structural formula of target product is as follows：
Embodiment 18
Present embodiments provide one kind and utilize 0.5mol%La2Na8(OCH2CF3)14(THF)6Benzene is catalyzed under the conditions of 80 DEG C The method of the reaction of methyl acetate and monoethanolamine, comprises the following steps that：
Weigh the La of 11.4mg (0.005mmol)2Na8(OCH2CF3)14(THF)6In the reaction bulb with stirrer, to 125 μ L (1.0mmol) methyl benzoates and 73 μ L (1.2mmol) monoethanolamines are added in the reaction bulb, in anhydrous, anaerobic and are adopted Under conditions of being protected with argon gas, 6h is reacted under the conditions of 80 DEG C.After reaction, through column chromatography (ethyl acetate/petroleum ether=2/ 1) target product 164mg, yield 99%, are obtained.The structural formula of target product is as follows：
Embodiment 19
Present embodiments provide one kind and utilize 0.5mol%La2Na8(OCH2CF3)14(THF)6Benzene is catalyzed under the conditions of 80 DEG C The method of the reaction of methyl acetate and N- methylbenzylamines, comprises the following steps that：
Weigh the La of 11.4mg (0.005mmol)2Na8(OCH2CF3)14(THF)6In the reaction bulb with stirrer, to 125 μ L (1.0mmol) methyl benzoates and 155 μ L (1.2mmol) N- methylbenzylamines are added in the reaction bulb, in anhydrous, anaerobic And under conditions of being protected using argon gas, react 6h under the conditions of 80 DEG C.After reaction, through column chromatography (ethyl acetate/petroleum ether =4/1) target product 68mg, yield 30%, are obtained.The structural formula of target product is as follows：
The above is only the preferred embodiment of the present invention, is not intended to limit the invention, it is noted that for this skill For the those of ordinary skill in art field, without departing from the technical principles of the invention, can also make it is some improvement and Modification, these improvements and modifications also should be regarded as protection scope of the present invention.

Claims (10)

1. a kind of catalysis ester and amine carry out the method that reaction prepares acid amides, it is characterised in that comprise the following steps：
The ester of formula (I) and the amine of formula (II) are containing catalysis of the alkoxy rare-earth metal cluster compound of alkali metallic sodium as catalyst Under react, obtain the compound of formula (III)；Or
The ester of formula (I) and the amine of formula (IV) are containing catalysis of the alkoxy rare-earth metal cluster compound of alkali metallic sodium as catalyst Under react, obtain the compound of formula (V)；
Reaction equation difference is as follows：
Wherein, R1Selected from alkyl, aryl or heteroaryl；
R2、R3、R4Independently selected from alkylol, alkyl, cycloalkyl, heterocyclic radical, aromatic radical or heteroaryl；Or
R3、R4Independently selected from alkylol, alkyl and R3、R4Atom connected to them forms ring.
2. catalysis ester according to claim 1 and amine carry out the method that reaction prepares acid amides, it is characterised in that：The alkyl For saturated alkyl or unsaturated alkyl containing 1-14 atom, the unsaturated alkyl includes alkenyl or alkynyl；The alkyl Alcohol contains 1-6 carbon atom.
3. catalysis ester according to claim 1 and amine carry out the method that reaction prepares acid amides, it is characterised in that：The cycloalkanes Base is saturation or unsaturation ring alkyl containing 1-14 atom；The heterocyclic radical is containing with nitrogen, oxygen or sulfur heteroatom The saturation of 1-14 atom or undersaturated heterocycle.
4. the catalysis ester and amine according to Claims 2 or 3 carry out the method that reaction prepares acid amides, it is characterised in that：It is described Alkyl and cycloalkyl are substituted with a substituent, and the substituent is selected from hydroxyl, phenyl or benzyl.
5. catalysis ester according to claim 1 and amine carry out the method that reaction prepares acid amides, it is characterised in that：The aryl For the aryl containing 5-14 atom；The heteroaryl is the aryl containing 5-14 atom with nitrogen, oxygen or sulfur heteroatom.
6. catalysis ester according to claim 5 and amine carry out the method that reaction prepares acid amides, it is characterised in that：When the virtue When base and heteroaryl are substituted with a substituent, the substituent may be selected from alkyl, halogen, trifluoromethyl, the halogen is fluorine, chlorine, Bromine or iodine.
7. catalysis ester according to claim 1 and amine carry out the method that reaction prepares acid amides, it is characterised in that：R3、R4With it The atom that is connected form the cycloalkyl containing 4-14 atom or contain oxa alkyl containing 4-14 atom.
8. catalysis ester according to claim 1 and amine carry out the method that reaction prepares acid amides, it is characterised in that：Contain alkali gold The alkoxy rare-earth metal cluster compound for belonging to sodium is Nd2Na8(OCH2CH2NMe2)12(OH)2、Y2Na8(OCH2CF3)14(THF)6、 Nd2Na8(OCH2CF3)14(THF)6Or La2Na8(OCH2CF3)14(THF)6。
9. catalysis ester according to claim 1 and amine carry out the method that reaction prepares acid amides, it is characterised in that：Reaction temperature For 40-80 DEG C.
10. catalysis ester according to claim 1 and amine carry out the method that reaction prepares acid amides, it is characterised in that：The ester, The molar ratio of amine and catalyst is 1:1-1.2:0.0025-0.01.
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