CN103804108B - A kind of method preparing primary amine - Google Patents

A kind of method preparing primary amine Download PDF

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CN103804108B
CN103804108B CN201210459222.0A CN201210459222A CN103804108B CN 103804108 B CN103804108 B CN 103804108B CN 201210459222 A CN201210459222 A CN 201210459222A CN 103804108 B CN103804108 B CN 103804108B
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diketone
acid
alkyl
diaryl
diphenyl
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CN103804108A (en
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张为革
吴军辉
沈杞容
包凯
孙俊
朱志彬
姜楠
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Shenyang Pharmaceutical University
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Abstract

The present invention relates to chemical field, relating to one from halogenated hydrocarbons (or hydrocarbon alcohol sulphonic acid ester) and ammonia (or Methanamide) is the method that primary amine prepared by raw material.The present invention includes following three step: (1) imidizate: the reactions such as 3,4 diaryl furan 2,5 diketone (I) and ammonia (or Methanamide) prepare 3,4 diaryl 1H pyrroles 2,5 diketone (II).(2) N hydrocarbylation: with 3,4 diaryl 1H pyrroles 2,5 cyclohexadione compounds (II) are under the effect of alkali, N hydrocarbyl reaction is there is with halogenated hydrocarbons (or hydrocarbon alcohol sulphonic acid ester), prepare N alkyl 3,4 diaryl 1H pyrroles 2,5 diketone (III)；(3) hydrolysis: N alkyl 3,4 diaryl 1H pyrroles 2,5 diketone (III) prepare primary amine through basic hydrolysis, 2 generated, 3 diaryl maleates form 3 through the automatic cyclization of acid treatment, 4 diaryl furan 2,5 diketone (I), the latter is directly used in aforesaid N hydrocarbyl reaction after imidizate.The present invention has 3, and 4 diaryl furan 2,5 diketone can be low with high-recovery recycled, material molar ratio, the feature that resulting primary amine yield is high.

Description

A kind of method preparing primary amine
Technical field
The present invention relates to chemical field, be specifically related to a kind of from halogenated hydrocarbons (or hydrocarbon alcohol sulphonic acid ester) and ammonia (or formyl Amine) it is the raw material new method of preparing primary amine.
Background technology
Primary amine compound is the industrial chemicals that a class is important, at chemical industry (especially fine chemistry industry and medical industry) There is purposes widely in field.
The preparation method of primary amine is of a great variety, and conventional method has following a few class: (1) is from nitrile, amide, oxime, hydrazone or nitro Method of reducing (JD White, KM Yager, the T Yakura. synthetic studies of that compound sets out pyrroloquinoline nucleus of the makaluvamine alkaloids. synthesis of the topoisomerase ii inhibitor makaluvamine D. Journal of the American Chemical Society, 1994, 116(5), 556-568. RM Moriarty, CJ Chany II, et al Preparation of methyl carbamates from primary alkyl and arylcarboxamides using hypervalent iodine. Journal of Organic Chemistry, 1993, 58(9), 2478-2482. WR Dolbier Jr., XX Rong. Reactivity of perfluoro-n-alkyl radicals a Hammett study of hydrogen transfer from arene thiols. Tetrahedron letters 1994, 35 (34), 6225 -6228.)；(2) from aldehyde, reduction amination method (SE Denmark, the T Weber, DW of ketone Piotrowski. Organocerium additions to SAMP-hydrazones: general synthesis of chiral amines. Journal of the American Chemical Society, 1987, 109(7), 2224- 2225. VA Soloshonok, AG Kirilenko, et al. A practical route to fluoroalkyl and fluoroarylamines by base catalyzed[1,3]-proton shift reaction. Tetrahedron letters 1994,35 (19), 3119-3122.)；(3) from the weight of the carboxylic acid derivates such as amide Row's biodegrading process, such as Hoffman degraded (RM Moriarty, CJ Chany II, et al. Preparation of methyl carbamates from primary alkyl and arylcarboxamides using hypervalent Iodine. Journal of Organic Chemistry, 1993,58 (9), 2478-2482), Curtius reset (K Ninomiya, T Shioiri, S Yamada. Phosphorus in organic synthesis-VII : Diphenyl phosphorazi- date (DPPA). A new convenient reagent for a modified curtius Reaction. Tetrahedron letters 1984,30 (14), 2151-2157), Schmidt reset (KB. Wiberg, BS Ross. et al. 2- Substituted bicyclo[1.1.1]pentanes. Journal of Organic Chemistry, 1993,58 (7), 2478-2482) etc.；(4) from halogenated alkane or alkylol sulphonic acid ester Through the method that primary amine is prepared in the reactions such as nucleophilic displacement of fluorine.Above-mentioned all kinds of method initiation materials are different, and range of application is different.
Halogenated hydrocarbons and hydrocarbon alcohol sulphonic acid ester are extremely common industrial chemicals, wide material sources, and preparation is convenient.From halogenated hydrocarbons and Hydrocarbon alcohol sulphonic acid ester sets out and prepares the method for primary amine through reactions such as N-alkylations and specifically include that the direct substitution method of ammonia, Delepine Method and Gabriel method.
N-alkylated reaction is directly carried out for raw material and ammonia, same at prepared primary amine with halogenated hydrocarbons and hydrocarbon alcohol sulphonic acid ester Time, also obtaining secondary amine, tertiary amine by-product, the yield of primary amine is low, isolated and purified difficulty, is seldom applied to the industrialization system of primary amine Standby.
Delepine method is with active halogenated alkane or alkylol sulphonic acid ester as raw material, with hexamethylenetetramine through N- Alkylated reaction forms quaternary ammonium salt, then hydrolyzes to form primary amine salt, ammonia salt and the reaction of formaldehyde under acidity.The method requires necessary Vivaciously compound is as initiation material, at raw material to use pi-allyl, benzyl or the halides at carbonyl ortho position or hydroxyl sulfoacid ester etc. Can not be with the functional group of acid labile in molecule, the scope of raw material is severely limited；Only one of which N in hexamethylenetetramine Atom can be used for reacting, and while generating the primary amine salt of 1 mole, forms ammonia salt and the formaldehyde of 6 moles, this reaction of 3 moles Atom economy not ideal enough.
Gabriel method is with halogenated hydrocarbons and hydrocarbon alcohol sulphonic acid ester as raw material, carries out N-alkane with phthalimide salt Glycosylation reaction forms N-alkyl-phthalimide, then uses the mode of hydrazinolysis (or hydrolysis) to discharge primary amine (or primary amine Salt), produce equimolar 2,3-dihydro phthalazines-Isosorbide-5-Nitrae-diketone (or phthalic acid) simultaneously.The reaction raw materials of the method is not Being only limitted to active halogenated hydrocarbons and hydrocarbon alcohol sulphonic acid ester, range of application is wider；Main shortcoming is forming while primary amine generation etc. Mole 2,3-dihydro phthalazines-Isosorbide-5-Nitrae-diketone (or phthalic acid), and 2,3-dihydro phthalazines-Isosorbide-5-Nitrae-diketone (or O-phthalic Acid) recycle difficulty, the Atom economy causing whole reaction is poor, makes Gabriel prepare the method for primary amine industrially Application is by a definite limitation.
To sum up, though the method preparing primary amine through reactions such as N-alkylations from halogenated hydrocarbons and hydrocarbon alcohol sulphonic acid ester has number Kind, but have that reaction selectivity is low or the shortcoming such as Atom economy is poor.
Summary of the invention
In order to overcome defect of the prior art, the invention provides a kind of from halogenated hydrocarbons and hydrocarbon alcohol sulphonic acid ester system The new method of standby primary amine, the method passes through 3,4-diaryl furan-2,5-diketone (I) → 3,4-diaryl-1H-pyrroles-2,5- Cyclohexadione compounds (II) → N-alkyl-3,4-diaryl-1H-pyrroles-2, the recycling of 5-diketone (III) three kinds of materials, Completing with halogenated hydrocarbons (or hydrocarbon alcohol sulphonic acid ester) and ammonia (or Methanamide) is that primary amine prepared by raw material.
The present invention includes following three step: (1) imidizate: 3,4-diaryl furan-2,5-diketone (I) and ammonia (or Methanamide) etc. reaction, substrate molecule introduces atom N, has prepared acid imide, i.e. 3,4-diaryl-1H-pyrroles-2,5-bis- Ketone (II).(2) N-hydrocarbylation: substitute classical Gabriel method with 3,4-diaryl-1H-pyrrole-2,5-diones compounds (II) In phthalimide, under the effect of alkali, with halogenated hydrocarbons (or hydrocarbon alcohol sulphonic acid ester) occur N-hydrocarbyl reaction, at N Upper introducing alkyl, prepares N-alkyl-3,4-diaryl-1H-pyrroles-2,5-diketone (III)；(3) hydrolysis: N-alkyl-3,4-two Aryl-1H-pyrroles-2,5-diketone (III) prepares primary amine through basic hydrolysis, and 2 simultaneously generated, 3-diaryl maleate is through letter Single automatic cyclization of acid treatment forms inner-acid anhydride, and i.e. 3,4-diaryl furan-2,5-diketone (I), the latter is through simple dried After be directly used in aforesaid N-hydrocarbyl reaction.Above-mentioned (1) imidizate → (2) N-hydrocarbylation → (3) three steps of hydrolysis are followed Ring is carried out, by 3, and 4-diaryl furan-2,5-diketone (I) → 3,4-diaryl-1H-pyrroles-2,5-cyclohexadione compounds (II) → N-alkyl-3,4-diaryl-1H-pyrroles-2, the recycling of 5-diketone (III) three kinds of materials, complete with halogenated hydrocarbons (or hydrocarbon alcohol sulphonic acid ester) and ammonia (or Methanamide) are that primary amine prepared by raw material.
The primary amine preparation method flow process of the present invention is as follows:
The present invention is preferably as follows raw material, reagent, intermediate:
Ar1With Ar2The most independent for phenyl, naphthyl；Described phenyl unsubstituted or by 1-5 (such as 1,2 Individual, 3,4 or 5) substituent group replace, substituent group is independently selected from following groups: halogen, nitro, amino, N-(C1-C6 alkane Base) amino, N, N-bis-(C1-C6 alkyl) amino, C1-C6 acyl amino, hydroxyl, carboxyl, C1-C6 alkyloxycarbonyl, C1-C6 alkane Base nitrone, cyano group, sulfydryl, C1-C6 alkyl, C1-C6 alkoxyl, C1-C6 haloalkyl, C3-C6 cycloalkyl；Described naphthyl Including 1-substituted naphthyl and 2-substituted naphthyl, naphthyl is unsubstituted or by 1-6 (such as 1,2,3,4,5 or 6 Individual) replace independently selected from substituents: halogen, nitro, amino, N-(C1-C6 alkyl) monosubstituted amino, N, N-(C1-C6 Alkyl) disubstituted amino, C1-C6 acyl amino, hydroxyl, carboxyl, C1-C6 alkyloxycarbonyl, C1-C6 alkyl nitrone, cyano group, Sulfydryl, C1-C6 alkyl, C1-C6 alkoxyl, C1-C6 haloalkyl, C3-C6 cycloalkyl.
The structure of RX is as follows:
Wherein, X (includes phenylsulfonyloxy group, to toluene sulphur selected from halogen (including iodine, bromine, chlorine and fluorine) and sulfonyloxy Acyloxy, p-nitrophenyl sulfonyloxy, to chloro benzenesulfonyloxy, to methoxybenzene sulfonyloxy, sulfonyloxy methyl epoxide, fluoro first Base sulfonyloxy, ethylsulfonyloxy, phenethyl sulfonyloxy)；
Y1、Y2It is each independently selected from-CR6=CR7-、-C≡C-、-O-、-NR8R9-、-S-、-CO-、-SO-、-SO2-；
Z selected from hydrogen, unsubstituted or by 1-5 (such as 1,2,3,4 or 5) substituted phenyl of substituent group, Substituent group is independently selected from following groups: halogen, nitro, amino, N-(C1-C6 alkyl) monosubstituted amino, N, N-(C1-C6 alkane Base) disubstituted amino, C1-C6 acyl amino, hydroxyl, carboxyl, C1-C6 alkyloxycarbonyl, C1-C6 alkyl nitrone, cyano group, mercapto Base, C1-C6 alkyl, C1-C6 alkoxyl, C3-C6 cycloalkyl or wherein said alkyl can be taken by halogen, hydroxyl, amino Generation；
R1、R2、R3、R4、R5、R6、R7、R8And R9It is each independently selected from hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl；
N, m, p, q are selected from 0,1,2,3, make RX constitute stable compound.
RNH2Structure as follows:
Wherein, the structure of R-portion is consistent with the structure of R-portion in aforementioned RX.
Alkali (Base) is selected from KOH, NaOH, LiOH, Ca (OH)2、Ba(OH)2、CsOH、Sr(OH)2、K2CO3、Na2CO3、 Li2CO3、KHCO3、NaHCO3、LiHCO3、LiNH2、Li2NH、t-BuOK、t-BuONa、t-BuOLi 、MeOK、EtOK、MeONa、 EtONa、、MeOLi、EtOLi、LDA、DMAP、LiHMDS、C4H9Li、C6H5Li。
Acid (Acid) is selected from organic acid and mineral acid, and wherein mineral acid is hydrochloric acid, sulphuric acid, hydrobromic acid, phosphoric acid, nitric acid, has Machine acid is formic acid, acetic acid, citric acid, oxalic acid, tartaric acid, benzoic acid, malic acid.
The raw material of the present invention, reagent, intermediate are preferably as follows:
Ar1With Ar2The most independent for phenyl, naphthyl；Described phenyl unsubstituted or by 1-2 (such as 1,2 Individual) replacement of individual substituent group, substituent group is independently selected from following groups: halogen, nitro, amino, hydroxyl, cyano group, sulfydryl, C1-C3 Alkyl, C1-C3 alkoxyl, C1-C3 haloalkyl；Described naphthyl includes 1-substituted naphthyl and 2-substituted naphthyl, naphthyl not by Replace or replaced independently selected from substituents by 1-2 (such as 1,2): halogen, nitro, amino, hydroxyl, carboxyl, Cyano group, sulfydryl, C1-C3 alkyl, C1-C3 alkoxyl, C1-C3 haloalkyl.
The structure of RX is as follows:
Wherein, X (includes phenylsulfonyloxy group, to toluene sulphur selected from halogen (including iodine, bromine, chlorine and fluorine) and sulfonyloxy Acyloxy, to chloro benzenesulfonyloxy, sulfonyloxy methyl epoxide)；
Y1、Y2It is each independently selected from-CR6=CR7-、-C≡C-、-O-、-NR8R9-、-S-；
Z is selected from hydrogen, unsubstituted or by 1-3 (such as 1,2,3) substituted phenyl of substituent group, substituent group is independent Ground is selected from following groups: halogen, nitro, amino, hydroxyl, carboxyl, C1-C3 alkyloxycarbonyl, C1-C3 alkyl nitrone, cyano group, Sulfydryl, C1-C3 alkyl, C1-C3 alkoxyl, C3-C6 cycloalkyl or wherein said alkyl can be by halogen, hydroxyl, amino Replace；
R1、R2、R3、R4、R5、R6、R7、R8And R9It is each independently selected from hydrogen, C1-C3 alkyl；
N, m, p, q are selected from 0,1,2,3, make RX constitute stable compound.
RNH2Structure as follows:
Wherein, the structure of R-portion is consistent with the structure of R-portion in aforementioned RX.
Base is selected from KOH, NaOH, LiOH, K2CO3、Na2CO3、Li2CO3、KHCO3、NaHCO3、LiHCO3、t-BuOK、t- BuONa、t-BuOLi 、MeOK、EtOK、MeONa、EtONa、、MeOLi、EtOLi、LDA、C4H9Li。
Acid is selected from organic acid and mineral acid, and wherein mineral acid is hydrochloric acid, sulphuric acid, hydrobromic acid, phosphoric acid, nitric acid, organic acid It is formic acid, acetic acid, citric acid, oxalic acid, tartaric acid.
(1) imidizate → (2) N-hydrocarbylation → (3) that are further characterized by of technical scheme hydrolyze three The operational approach of step reaction is as follows:
(1) imidizate: by 3,4-diaryl furan-2,5-diketone (I) adds in reactor with ammonia (or Methanamide), adds Thermal response, has prepared 3,4-diaryl-1H-pyrroles-2,5-diketone (II).In this reaction, 3,4-diaryl furan-2,5-diketone (I) mol ratio with ammonia (or Methanamide) is 1: 1 ~ 100；Ammonia is formulated as solution and uses, and solute is NH3, solvent is selected from water, first Any ratio mixture of alcohol, ethanol, propanol, the tert-butyl alcohol, isopropanol, sec-butyl alcohol or above-mentioned each solvent, the concentration model of ammonia solution Enclose for saturated solution ~ 0.1%；Methanamide can be used directly, it is also possible to be configured to solution use, solvent selected from water, methanol, ethanol, Acetone, dioxane, ethylene glycol, oxolane, DMF, DMSO or any mixture, the concentration range of formamide solution is 100~0.1%；Range of reaction temperature is 50 ~ 150 DEG C；Mode of heating is conventional heating, including use air bath, oil bath, sand-bath, Steam bath, water-bath (during less than 100 DEG C), or microwave irradiation heating；Reactor is conventional reactor (normal pressure), or closed reactor (pressure)；Response time is 0.05 ~ 24 hour.
(2) N-hydrocarbylation: first 3,4-diaryl-1H-pyrrole-2,5-diones compounds (II), alkali and solvent are added Reactor reacts；During this, 3,4-diaryl-1H-pyrroles-2,5-cyclohexadione compounds (II) is 1 with the mol ratio of alkali : 1 ~ 20, solvent selected from ethanol, propanol, the tert-butyl alcohol, isopropanol, sec-butyl alcohol, acetonitrile, acetone, DMF and DMSO or above-mentioned each molten Any ratio mixture of agent, compound (II) is 1: 1 ~ 200 with the mass ratio of solvent, and range of reaction temperature is 10 ~ 150 DEG C, Mode of heating (if desired for) identical with the mode of heating that aforementioned " imidizate " reacts, reactor is conventional reactor (normal pressure), Or closed reactor (pressure), the response time is 0.05 ~ 24 hour.Halogenated hydrocarbons (or hydrocarbon alcohol sulfonic acid is added again in reactor Ester), continue reaction, prepare N-alkyl-3,4-diaryl-1H-pyrroles-2,5-diketone (III)；During this, 3,4-diaryl- 1H-pyrroles-2,5-cyclohexadione compounds (II) is 1: 1 ~ 100 with the mol ratio of halogenated hydrocarbons (or hydrocarbon alcohol sulphonic acid ester), reaction Temperature range is 10 ~ 150 DEG C, mode of heating (if desired for) identical with the mode of heating that aforementioned " imidizate " reacts；Reactor For conventional reactor (normal pressure), or closed reactor (pressure)；Response time is 0.1 ~ 24 hour.
(3) hydrolysis: N-alkyl-3,4-diaryl-1H-pyrrole-2,5-diones (III), alkali and solvent are added reactor Middle reaction, wherein, N-alkyl-3,4-diaryl-1H-pyrroles-2, the mol ratio of 5-diketone (III) and alkali is 1: 2 ~ 50, molten Agent is selected from water, methanol, ethanol, propanol, the tert-butyl alcohol, isopropanol, sec-butyl alcohol, ether, acetonitrile, acetone, DMF and DMSO or above-mentioned Any ratio mixture of each solvent, N-alkyl-3,4-diaryl-1H-pyrroles-2,5-diketone (III) is 1 with the mass ratio of solvent : 1 ~ 200, range of reaction temperature is 50 ~ 150 DEG C, mode of heating (if desired for) mode of heating that reacts with aforementioned " imidizate " Identical, reactor is conventional reactor (normal pressure), or closed reactor (pressure), and the response time is 0.05 ~ 24 hour.Again to instead Answering and add acid in device, the pH value to reactant liquor is 1-6 and has solid to separate out, and vibration, to solid-liquid two phase stratification, divides according to a conventional method Being 3 from obtaining solid, 4-diaryl furan-2,5-diketone (I), 3,4-diaryl furan-2,5-diketone (I) is used directly for Imidizate；Reactant liquor extracts routinely, distills, separates, and obtains resulting primary amine；Or reactant liquor becomes salt with acid after extraction, Obtain resulting primary amine salt.
(1) imidizate → (2) N-hydrocarbylation → (3) that are further characterized by of technical scheme hydrolyze three The optimization operation method of step reaction is as follows:
Microwave catalysis reacts:
(1) imidizate: by 3,4-diaryl furan-2,5-diketone (I) and ammonia (or Methanamide) add in reactor, micro- Bomi closes reacting by heating, has prepared 3,4-diaryl-1H-pyrroles-2,5-diketone (II).In this reaction, 3,4-diaryl furan- 2,5-diketone (I) is 1: 2 ~ 10 with the mol ratio of ammonia (or Methanamide)；Ammonia is formulated as solution and uses, and solute is NH3, solvent selects From water, methanol, ethanol, the concentration range of ammonia solution is saturated solution ~ 1%；Methanamide can be used directly, it is also possible to is configured to molten Liquid uses, and solvent is selected from DMF, DMSO, and the concentration range of formamide solution is 100 ~ 10%；Range of reaction temperature is 80 ~ 120 DEG C； Response time is 0.05 ~ 0.5 hour.
(2) N-hydrocarbylation: first 3,4-diaryl-1H-pyrrole-2,5-diones compounds (II), alkali and solvent are added Reactor reacts；During this, 3,4-diaryl-1H-pyrroles-2,5-cyclohexadione compounds (II) is 1 with the mol ratio of alkali : 1 ~ 5, solvent selected from ethanol, acetonitrile, acetone, DMF, compound (II) is 1: 10 ~ 100 with the mass ratio of solvent, reaction temperature Degree scope is 40 ~ 100 DEG C, and reactive mode is sealed microwave reacting by heating, and the response time is 0.05 ~ 0.5 hour.Again to reactor Middle addition halogenated hydrocarbons (or hydrocarbon alcohol sulphonic acid ester), continues reaction, prepares N-alkyl-3,4-diaryl-1H-pyrroles-2,5-diketone (III)；During this, 3,4-diaryl-1H-pyrroles-2,5-cyclohexadione compounds (II) and halogenated hydrocarbons (or hydrocarbon alcohol sulfonic acid Ester) mol ratio be 1: 1 ~ 2, range of reaction temperature is 40 ~ 100 DEG C, and reactive mode is sealed microwave reacting by heating, during reaction Between be 0.05 ~ 0.5 hour.
(3) hydrolysis: N-alkyl-3,4-diaryl-1H-pyrrole-2,5-diones (III), alkali and solvent are added reactor Middle reaction；Wherein, N-alkyl-3,4-diaryl-1H-pyrroles-2, the mol ratio of 5-diketone (III) and alkali is 1:2 ~ 10, solvent Selected from water and ethanol, ether, acetonitrile, the mixed solution of acetone composition, the concentration of water is 90 ~ 50%, N-alkyl-3,4-diaryl- 1H-pyrroles-2,5-diketone (III) is 1: 10 ~ 100 with the mass ratio of solvent, and range of reaction temperature is 50 ~ 120 DEG C, reaction side Formula is sealed microwave reacting by heating, and the response time is 0.05 ~ 0.5 hour.Acid is added again in reactor.PH value to reactant liquor For 4-6 and there is solid to separate out, vibrating to solid-liquid two phase stratification, filter pickling obtaining solid is 3,4-diaryl furan-2,5-bis- Ketone (I), 3,4-diaryl furan-2,5-diketone (I) can direct imidizate；Reactant liquor extracts routinely, distills, separates, Obtain resulting primary amine；Or reactant liquor becomes salt with acid after extraction, obtains resulting primary amine salt.
Conventional heating reacts:
(1) imidizate: by 3,4-diaryl furan-2,5-diketone (I) adds in reactor with ammonia (or Methanamide), adds Thermal response, has prepared 3,4-diaryl-1H-pyrroles-2,5-diketone (II).In this reaction, 3,4-diaryl furan-2,5-diketone (I) mol ratio with ammonia (or Methanamide) is 1: 2 ~ 20；Ammonia is formulated as solution and uses, and solute is NH3, solvent is selected from water, first Alcohol, ethanol, the concentration range of ammonia solution is saturated solution ~ 1%；Methanamide can be used directly, it is also possible to is configured to solution and uses, Solvent is selected from DMF, DMSO, and the concentration range of formamide solution is 100 ~ 1%；Range of reaction temperature is 90 ~ 150 DEG C；Mode of heating For conventional heating, including using air bath, oil bath, water-bath (during less than 100 DEG C)；Reactor is conventional reactor (normal pressure), or Closed reactor (pressure)；Response time is 0.5 ~ 24 hour.
(2) N-hydrocarbylation: first 3,4-diaryl-1H-pyrrole-2,5-diones compounds (II), alkali and solvent are added Reactor reacts；During this, 3,4-diaryl-1H-pyrroles-2,5-cyclohexadione compounds (II) is 1 with the mol ratio of alkali : 1 ~ 5, any ratio mixture of solvent selected from ethanol, propanol, acetonitrile, acetone, DMF and DMSO or above-mentioned each solvent, chemical combination Thing (II) is 1: 10 ~ 100 with the mass ratio of solvent, and range of reaction temperature is 25 ~ 100 DEG C, and mode of heating is conventional heating, bag Including use air bath, oil bath, water-bath (during less than 100 DEG C), reactor is conventional reactor (normal pressure), and the response time is 0.1 ~ 1 Hour.In reactor, add halogenated hydrocarbons (or hydrocarbon alcohol sulphonic acid ester) again, continue to react, preparation N-alkyl-3,4-diaryl- 1H-pyrrole-2,5-diones (III)；During this, 3,4-diaryl-1H-pyrroles-2,5-cyclohexadione compounds (II) and halo The mol ratio of hydrocarbon (or hydrocarbon alcohol sulphonic acid ester) is 1: 1 ~ 1.5, and range of reaction temperature is 25 ~ 100 DEG C, and mode of heating is that routine adds Heat, including using air bath, oil bath, water-bath (during less than 100 DEG C), reactor is conventional reactor (normal pressure), and the response time is 0.5 ~ 5 hour.
(3) hydrolysis: N-alkyl-3,4-diaryl-1H-pyrrole-2,5-diones (III), alkali and solvent are added reactor Middle reaction；Wherein, N-alkyl-3,4-diaryl-1H-pyrroles-2, the mol ratio of 5-diketone (III) and alkali is 1:5 ~ 20, solvent Selected from water and ethanol, ether, acetonitrile or the mixed solution of acetone composition, the concentration of water is 80 ~ 50%, N-alkyl-3,4-bis-virtue Base-1H-pyrroles-2,5-diketone (III) is 1: 10 ~ 100 with the mass ratio of solvent, and range of reaction temperature is 50 ~ 120 DEG C, adds Hot mode is conventional heating, and including using air bath, oil bath, water-bath (during less than 100 DEG C), reactor is that conventional reactor is (normal Pressure), or closed reactor (pressure), the response time is 0.5 ~ 5 hour；In reactor, acid adding to the pH value of reactant liquor is 4-again 6 and have solid to separate out, vibration is to solid-liquid two phase stratification, and isolated solid is 3 according to a conventional method, 4-diaryl furan-2,5- Diketone (I), 3,4-diaryl furan-2,5-diketone (I) can direct imidizate；Reactant liquor extracts routinely, distills, divides From, obtain resulting primary amine；Or reactant liquor becomes salt with acid after extraction, obtains resulting primary amine salt.
Technical scheme is further characterized by, in microwave catalysis reacts, and the microwave reactor used For CEM DISCOVER ring focusing single mold microwave synthesis system (microwave synthesizer).
Technical scheme is further characterized by, and the organic solvent of every in invention " organic solvent extraction " is not During specified otherwise, it is typically chosen methyl tertiary butyl ether(MTBE), dichloromethane or ethyl acetate.
Technical scheme is further characterized by, and primary amine solutions is normally spin-dried for obtaining primary amine；Or can lead to Cross into salt and obtain primary amine salt, hydrochloric acid, sulphuric acid, hydrobromic acid, formic acid, acetic acid, citric acid, oxalic acid can be selected, wherein to be passed through HCl Gas becomes salt optimal.
Technical scheme can obtain following product RNH2, but it is not limited to following compound:
(01)Benzylamine
(02)3,4,5-trimethoxy benzylamine
(03)4-methoxybenzylamine
(04)2-flunamine
(05)4-flunamine
(06)4-bretylium tosylate
(07)2-bretylium tosylate
(08)2-chlorobenzylamine
(09)4-cyano group benzylamine
(10)4-benzyloxy benzylamine
(11)4-chlorobenzylamine
(12)3-flunamine
(13)3-chlorobenzylamine
(14)2,3-dichloro-benzylamine
(15)3,4-dichloro-benzylamine
(16)2-phenethylamine
(17)2-(benzyloxy) ethamine
(18)3-phenylpropyl-1-amine
(19)1-(4-(3-aminopropan epoxide) 3-methoxyphenyl) ethanol
(20)4-benzene butyl-1-amine
(21)(E)-3-phenylpropyl-2-alkene-1-amine
The outstanding feature of primary amine preparation method of the present invention can be summarized as:
1.(1) imidizate → (2) N-hydrocarbylation → (3) three step cycle of hydrolysis are carried out, 3,4-diaryl furan-2, 5-diketone (I) → 3,4-diaryl-1H-pyrrole-2,5-diones compounds (II) → N-alkyl-3,4-diaryl-1H-pyrrole Coughing up-2, three kinds of material high-efficiency rates of 5-diketone (III) convert, it is achieved that the recycling of critical component；
2. in whole course of reaction, starting halo alkane (or alkylol sulphonic acid ester) and ammonia (or Methanamide) mol ratio Low, resulting primary amine yield is high；
3. the mild condition of each step reaction, the time is shorter, easy and simple to handle, does not uses chemical principle poisonous, harmful and expensive Material, reagent, with low cost, environmental friendliness.
Detailed description of the invention
The preparation method-1 of embodiment 1. benzylamine (01)
(1) imidizate: by 3,4-diphenyl furan-2,5-diketone (100.0mg, 0.4mmol), 1% ammonia (1.4g, 0.8mmol) joining in 10mL microwave reaction pipe, set the power of microwave reactor as 50W, at 120 DEG C, microwave radiation is anti- Answer 4 minutes；After cooling, use 20mL dichloromethane to be extracted twice, merge organic layer, add anhydrous sodium sulfate and be dried, decompression Lower recovery methylene chloride, obtains 3,4-diphenyl-1H-pyrroles-2,5-diketone, and yield 100% is directly used in follow-up N-hydrocarbon Glycosylation reaction.
3,4-diphenyl-1H-pyrrole-2,5-diones analytical data:1H-NMR(300MHz, CDCl3): δ7.40(10H, m); ESI-MS: 250(M+H+), 272(M+Na+)。
(2) N-hydrocarbylation: by above-mentioned 3,4-diphenyl-1H-pyrrole-2,5-diones and KOH(33.6mg, 0.6mmol), 6mL ethanol joins in 10mL microwave reaction pipe, sets the power of microwave reactor as 50W, reacts 10 at 90 DEG C of microwave radiations Minute；After decompression lower recovery etoh solvent, add 10mL acetonitrile and dissolve remaining solid, be transferred in 30 mL microwave reaction pipes, then Add bromobenzyl (68.0mg, 0.4mmol), sets the power of microwave reactor as 50W, 90 DEG C of microwave radiations reactions 10 minutes； Reclaiming solvent acetonitrile under decompression, obtain 1-benzyl-3,4-diphenyl-1H-pyrroles-2,5-diketone, yield 99%, after being directly used in Continuous hydrolysis.
1-benzyl-3,4-diphenyl-1H-pyrrole-2,5-diones analytical data:1H-NMR(300MHz, CDCl3): δ 4.80(2H, s),7.33(9H, m), 7.46(6H, m); ESI-MS: 340(M+H+), 362(M+Na+)。
(3) hydrolysis: by above-mentioned 1-benzyl-3,4-diphenyl-1H-pyrrole-2,5-diones and KOH(134.4mg, 2.4mmol), water (1.5mL) and ethanol (0.7mL) join in 10mL microwave reaction pipe, set the power of microwave reactor as 50W, in 102 DEG C of microwaves 10 minutes；After cooling, dripping 18% hydrochloric acid and being adjusted to pH value is 5.0, and vibration is to solid-liquid two phase stratification, mistake Filter to obtain solid, and wash solid at twice with 3% hydrochloric acid of 2mL, after solid drying constant weight, obtain raw material 3,4-diphenyl furan Muttering-2,5-diketone (98.1mg), the response rate is 98%；Filtrate mixes with pickle, drips 50%KOH aqueous solution and adjust in mixed liquor It is 11.0 to pH value, extracts three times with 50mL methyl tertiary butyl ether(MTBE), merge organic layer, add anhydrous magnesium sulfate and be dried；Cross and filter After removing desiccant anhydrous magnesium sulfate, being passed through dry HCl gas, have white fluffy solid to separate out in filtrate, sucking filtration obtains white Solid, after solid drying constant weight, obtains benzylamine hydrochloride (51.1mg), and product yield is that 89%(is in terms of raw material bromobenzyl).
Benzylamine (01) analytical data: ESI-MS:108 (M+H+), 130(M+Na+)。
Note: be not isolated purification process after each step of following embodiment, therefore first two steps are not carried out respectively yield calculating, Only calculate the response rate and total recovery in final step；The most only when each primary amine and relevant intermediate occur for the first time Enclose relevant analytical data.
The preparation method-2 of embodiment 2. benzylamine (01)
(1) imidizate: by 3,4-diphenyl furan-2,5-diketone (100.0mg, 0.4mmol) and Methanamide (1.8g, 40.0mmol) adding in closed reactor, oil bath is heated to 100 DEG C and reacts 5 hours；After cooling, add the dilution of 10mL water, add Entering 20mL methyl tertiary butyl ether(MTBE) to be extracted twice, merge organic layer, add anhydrous sodium sulfate and be dried, decompression is lower reclaims solvent methyl uncle Butyl ether, obtains 3,4-diphenyl-1H-pyrroles-2, and 5-diketone is directly used in follow-up N-hydrocarbyl reaction.
(2) N-hydrocarbylation: by above-mentioned 3,4-diphenyl-1H-pyrrole-2,5-diones and K2CO3(82.8mg, 0.6mmol), DMF(10.0mL) adding in reaction bulb, oil bath is heated to 40 DEG C of stirring reactions 30 minutes；After cooling, addition benzyl chloride (50.8mg, 0.4mmol), oil bath is heated to 40 DEG C of stirring reactions 2 hours；In reactant mixture, add 20mL water, then use 50mL methyl-tert Butyl ether extracts in three times, merges organic layer, the lower recycling design of decompression, obtains 1-benzyl-3,4-diphenyl-1H-pyrroles-2,5- Diketone, is directly used in follow-up hydrolysis.
(3) hydrolysis: by above-mentioned 1-benzyl-3,4-diphenyl-1H-pyrrole-2,5-diones and KOH(268.8mg, 4.8m Mol), water (2.0mL), ethanol (1.0mL) add in reaction bulb, and oil bath is heated to 80 DEG C of stirring reactions 20 hours；After cooling, Dripping 18% hydrochloric acid and being adjusted to pH value is 5.0, and vibration, to solid-liquid two phase stratification, filters to obtain solid, and with 3% hydrochloric acid of 3mL at twice Washing solid, after solid drying constant weight, obtains raw material 3,4-diphenyl furan-2,5-diketone (96.2mg), and the response rate is 96%；Filtrate mixes with pickle, and dripping 50%KOH aqueous solution in mixed liquor and being adjusted to pH value is 11.0, by 50mL methyl-tert fourth Base ether extracts three times, merges organic layer, adds anhydrous magnesium sulfate and is dried；After being filtered to remove desiccant anhydrous magnesium sulfate, to filtrate In be passed through dry HCl gas, have white fluffy solid to separate out, sucking filtration obtains white solid, after solid drying constant weight, obtains benzyl Amine hydrochlorate (47.1mg), product yield is that 82%(is in terms of raw material benzyl chloride).
The preparation method-3 of embodiment 3. benzylamine (01)
(1) imidizate: by 3,4-bis-(naphthalene-2-base) furan-2,5-diketone (140.0mg, 0.4mmol) and Methanamide (180.0mg, 4.0mmol), DMF(5mL) join in 10mL microwave reaction pipe, set the power of microwave reactor as 50W, At 100 DEG C, microwave radiation reacts 3 minutes；After cooling, add water (20mL), use 20mL methyl tertiary butyl ether(MTBE) extraction two Secondary, merge organic layer, add anhydrous sodium sulfate and be dried, the lower recycling design of decompression, obtain 3,4-bis-(naphthalene-2-base)-1H-pyrroles-2, 5-diketone, is directly used in follow-up N-hydrocarbyl reaction.
3,4-bis-(naphthalene-2-base)-1H-pyrrole-2,5-diones analytical data: ESI-MS:350 (M+H+), 372(M+Na+)。
(2) N-hydrocarbylation: by above-mentioned 3,4-bis-(naphthalene-2-base)-1H-pyrrole-2,5-diones and KOH(33.6mg, 0.6mmol), ethanol (6.0mL) add in reaction bulb, in ultrasonic reactor, at 25 DEG C, Ultrasonic Radiation reacts 10 minutes；Subtract After pressure recycling design ethanol, add 10mL acetonitrile and dissolve remaining solid, be transferred in 30 mL microwave reaction pipes, add bromine Benzyl (68.0mg, 0.4mmol), sets the power of microwave reactor as 50W, reacts 10 minutes at 90 DEG C of microwave radiations；Under decompression Recycling design acetonitrile, obtains 1-benzyl-3,4-bis-(naphthalene-2-base)-1H-pyrroles-2,5-diketone, is directly used in follow-up hydrolysis anti- Should.
1-benzyl-3,4-two (naphthalene-2-base)-1H-pyrrole-2,5-diones analytical data: ESI-MS:440 (M+H+), 462(M+Na+)。
(3) hydrolysis: by above-mentioned 1-benzyl-3,4-two (naphthalene-2-base)-1H-pyrrole-2,5-diones and NaOH(160.0mg, 4.0mmol) and methanol (4.0mL) joins in 10mL microwave reaction pipe, the power of microwave reactor is set as 50W, at 80 DEG C Microwave 10 minutes；After cooling, dripping 5% hydrochloric acid and being adjusted to pH value is 5.0, and vibration, to solid-liquid two phase stratification, filters to obtain solid, and Wash solid at twice with 3% hydrochloric acid of 2mL, after solid drying constant weight, obtain raw material 3,4-bis-(naphthalene-2-base) furan-2,5- Diketone (134.4mg), the response rate is 96%；Filtrate mixes with pickle, drips 50%KOH aqueous solution and be adjusted to pH value in mixed liquor It is 11.0, extracts three times with 50mL dichloromethane, merge organic layer, add anhydrous magnesium sulfate and be dried；Be filtered to remove desiccant without After water magnesium sulfate, reclaiming methylene chloride under decompression, residue, through column chromatography purification, obtains benzylamine (33.4mg), and product is received Rate is that 78%(is in terms of raw material bromobenzyl).
The preparation method-4 of embodiment 4. benzylamine (01)
(1) imidizate: by 3,4-bis-(4-methoxyphenyl) furan-2,5-diketone (124.0mg, 0.4mmol) and 10% NH3Ethanol solution (2.0g, 11.8mmol) join in 10mL microwave reaction pipe, set microwave reactor power For 50W, at 100 DEG C, microwave radiation reacts 20 minutes；Reclaim etoh solvent under decompression, obtain 3,4-bis-(4-methoxyphenyl)- 1H-pyrroles-2,5-diketone, it is directly used in follow-up N-hydrocarbyl reaction.
3,4-bis-(4-methoxyphenyl)-1H-pyrrole-2,5-diones analytical data: ESI-MS:310 (M+H+), 332 (M+Na+)。
(2) N-hydrocarbylation: by above-mentioned 3,4-bis-(4-methoxyphenyl)-1H-pyrrole-2,5-diones and K2CO3(82.8mg, 0.6mmol) and acetonitrile (10mL), PEG400 (2mL) add in reaction bulb, it is little that air bath is heated to 70 DEG C of stirring reactions 2 Time；After cooling, adding benzyl chloride (50.8mg, 0.4mmol), air bath is heated to 70 DEG C of stirring reactions 20 hours；To reaction mixing Thing adds 20mL water, is extracted twice with dichloromethane after 20mL water, the lower recycling design of decompression, obtain 1-benzyl-3,4-bis-(4- Methoxyphenyl)-1H-pyrroles-2,5-diketone, it is directly used in follow-up hydrolysis.
1-benzyl-3,4-two (4-methoxyphenyl)-1H-pyrrole-2,5-diones analytical data: ESI-MS:400 (M+H+), 422(M+Na+)。
(3) hydrolysis: by above-mentioned 1-benzyl-3,4-two (4-methoxyphenyl)-1H-pyrrole-2,5-diones and Na2CO3 (212.0mg, 2.0mmol), water (2.0mL), acetonitrile (1.0mL) add in reaction bulb, heating in water bath to 80 DEG C stirring reaction 10 Hour；After cooling, dripping 5% sulphuric acid and being adjusted to pH value is 5.0, and vibration, to solid-liquid two phase stratification, filters to obtain solid, and with 3mL's 5% sulphuric acid washs solid at twice, after solid drying constant weight, obtains raw material 3,4-bis-(4-methoxyphenyl) furan-2,5-bis- Ketone (117.5mg), the response rate is 95%；Filtrate mixes with pickle, drips 10% Na in mixed liquor2CO3Aqueous solution is adjusted to pH Value is 10.0, extracts three times with 50mL methyl tertiary butyl ether(MTBE), merges organic layer, adds anhydrous magnesium sulfate and is dried；It is filtered to remove dry After drying prescription anhydrous magnesium sulfate, dripping 98% sulphuric acid (1mL) in filtrate, vibration is to there being white fluffy solid to separate out, and it is unnecessary to remove After sulfuric acid layer, sucking filtration obtains white solid, after solid drying constant weight, obtains benzylamine sulfate (66.4mg), and product yield is 81% (in terms of raw material benzyl chloride).
The preparation method-5 of embodiment 5. benzylamine (01)
(1) imidizate: by 3-(naphthalene-2-base)-4-(6-nitronaphthalene-2-base) furan-2,5-diketone (158.0mg, 0.4mmol), 10% ammonia (1.36g, 8.0mmol) join in 10mL microwave reaction pipe, set the power of microwave reactor as 50W, at 120 DEG C, microwave radiation reacts 10 minutes；After cooling, use 20mL dichloromethane to be extracted twice, merge organic layer, Add anhydrous sodium sulfate to be dried, reclaim methylene chloride under decompression, obtain 3-(naphthalene-2-base)-4-(6-nitronaphthalene-2-base)-1H- Pyrroles-2,5-diketone, it is directly used in follow-up N-hydrocarbyl reaction.
3-(naphthalene-2-base)-4-(6-nitronaphthalene-2-base)-1H-pyrrole-2,5-diones analytical data: ESI-MS:395 (M +H+), 417(M+Na+)。
(2) N-hydrocarbylation: by above-mentioned 3-(naphthalene-2-base)-4-(6-nitronaphthalene-2-base)-1H-pyrrole-2,5-diones with LiOH(19.2mg, 0.8mmol), 6mL ethanol join in 10mL microwave reaction pipe, set the power of microwave reactor as 50W, reacts 10 minutes at 60 DEG C of microwave radiations；After decompression lower recovery etoh solvent, add 10mL acetone solution remaining solid, turn Move in 30 mL microwave reaction pipes, add p-methyl benzenesulfonic acid benzyl alcohol ester (158mg, 0.4mmol), set microwave reactor Power is 50W, reacts 10 minutes at 60 DEG C of microwave radiations；Reclaim solvent acetone under decompression, obtain 1-benzyl-3-(naphthalene-2-base)- 4-(6-nitronaphthalene-2-base)-1H-pyrroles-2,5-diketone, it is directly used in follow-up hydrolysis.
1-benzyl-3-(naphthalene-2-base)-4-(6-nitronaphthalene-2-base)-1H-pyrrole-2,5-diones analytical data: ESI- MS: 485(M+H+), 507(M+Na+)。
(3) hydrolysis: by above-mentioned 1-benzyl-3-(naphthalene-2-base)-4-(6-nitronaphthalene-2-base)-1H-pyrrole-2,5-diones With LiOH(240.0mg, 10.0mmol), water (3.0mL) and ethanol (1.0mL) join in 10mL microwave reaction pipe, set micro- The power of ripple reactor was 50W, in 110 DEG C of microwaves 10 minutes；After cooling, dripping 10% sulphuric acid and being adjusted to pH value is 5.0, vibration To solid-liquid two phase stratification, filter to obtain solid, and wash solid at twice with 3% sulphuric acid of 2mL, after solid drying constant weight, obtain Raw material 3-(naphthalene-2-base)-4-(6-nitronaphthalene-2-base) furan-2,5-diketone (153.3mg), the response rate is 97%；Filtrate and acid Washing liquid mixes, and dripping 25% NaOH aqueous solution in mixed liquor and being adjusted to pH value is 11.0, extracts three times with 50mL dichloromethane, closes And organic layer, add anhydrous magnesium sulfate and be dried；After being filtered to remove desiccant anhydrous magnesium sulfate, in filtrate, it is passed through dry HCl Gas, has white fluffy solid to separate out, and sucking filtration obtains white solid, after solid drying constant weight, obtains benzylamine hydrochloride (46.5mg), product yield is that 81%(is in terms of raw material p-methyl benzenesulfonic acid benzyl alcohol ester).
The preparation method-1 of embodiment 6. 3,4,5-trimethoxy benzylamine (02)
(1) imidizate: by 3,4-diphenyl furan-2,5-diketone (100.0mg, 0.4mmol), 1% ammonia (2.0g, 1.2mmol) joining in 10mL microwave reaction pipe, set the power of microwave reactor as 60W, at 120 DEG C, microwave radiation is anti- Answer 4 minutes；After cooling, use 20mL dichloromethane to be extracted twice, merge organic layer, add anhydrous sodium sulfate and be dried, decompression Lower recovery methylene chloride, obtains 3,4-diphenyl-1H-pyrroles-2,5-diketone, and yield 100% is directly used in follow-up N-hydrocarbon Glycosylation reaction.
(2) N-hydrocarbylation: by above-mentioned 3,4-diphenyl-1H-pyrrole-2,5-diones and KOH(33.6mg, 0.6mmol), 6mL ethanol joins in 10mL microwave reaction pipe, sets the power of microwave reactor as 60W, reacts 10 at 90 DEG C of microwave radiations Minute；After decompression lower recovery etoh solvent, add 10mL acetonitrile and dissolve remaining solid, be transferred in 30 mL microwave reaction pipes, then Add 3,4,5-trimethoxy bromobenzyl (104.0mg, 0.4mmol), set the power of microwave reactor as 60W, at 90 DEG C of microwaves Radioreaction 10 minutes；Reclaim solvent acetonitrile under decompression, obtain 3,4-diphenyl-1-(3,4,5-trimethoxy benzyl)-1H- Pyrroles-2,5-diketone, yield 98%, it is directly used in follow-up hydrolysis.
3,4-diphenyl-1-(3,4,5-trimethoxy benzyl)-1H-pyrrole-2,5-diones analytical data:1H-NMR (300MHz, CDCl3): δ3.83(3H, s), 3.87(6H, s), 4.72(2H, s), 6.73(2H, s), 7.39 (10H, m); ESI-MS: 430(M+H+), 452(M+Na+)。
(3) hydrolysis: by above-mentioned 3,4-diphenyl-1-(3,4,5-trimethoxy benzyl)-1H-pyrrole-2,5-diones with KOH(134.4mg, 2.4mmol), water (2.0mL) and ethanol (1.0mL) join in 10mL microwave reaction pipe, set microwave anti- The power answering device was 60W, in 102 DEG C of microwaves 10 minutes；After cooling, dripping 18% hydrochloric acid and being adjusted to pH value is 5.0, vibrates to solid Liquid two phase stratification, filters to obtain solid, and washs solid at twice with 3% hydrochloric acid of 3mL, after solid drying constant weight, obtain raw material 3,4-diphenyl furan-2,5-diketone (97.3mg), the response rate is 97%；Filtrate mixes with pickle, drips in mixed liquor It is 11.0 that 50%KOH aqueous solution is adjusted to pH value, extracts three times with 50mL methyl tertiary butyl ether(MTBE), merges organic layer, adds anhydrous slufuric acid Magnesium is dried；After being filtered to remove desiccant anhydrous magnesium sulfate, in filtrate, it is passed through dry HCl gas, has white fluffy solid to analyse Going out, sucking filtration obtains white solid, after solid drying constant weight, obtains 3,4,5-trimethoxy benzylamine hydrochlorides (81.3mg), product Yield is that 87%(is in terms of raw material 3,4,5-trimethoxy bromobenzyl).
3,4,5-trimethoxy benzylamine (02) analytical data: 1H-NMR(300MHz, CDCl3): δ3.83(2H, s), 3.84(3H, s),3.87(6H, s), 6.56(2H, s), 6.88(2H, d, J=8.54), 7.28(2H, d, J= 8.54), 7.65(1H, s); ESI-MS: 198(M+H+), 220(M+Na+)。
The preparation method-2 of embodiment 7. 3,4,5-trimethoxy benzylamine (02)
(1) imidizate: by 3,4-diphenyl furan-2,5-diketone (100.0mg, 0.4mmol) and Methanamide (3.6g, 80.0mmol) adding in closed reactor, oil bath is heated to 100 DEG C and reacts 6 hours；After cooling, add the dilution of 10mL water, add Entering 20mL methyl tertiary butyl ether(MTBE) to be extracted twice, merge organic layer, add anhydrous sodium sulfate and be dried, decompression is lower reclaims solvent methyl uncle Butyl ether, obtains 3,4-diphenyl-1H-pyrroles-2, and 5-diketone is directly used in follow-up N-hydrocarbyl reaction.
(2) N-hydrocarbylation: by above-mentioned 3,4-diphenyl-1H-pyrrole-2,5-diones and Na2CO3(63.6mg, 0.6mmol), DMF(10.0mL) add in reaction bulb, oil bath is heated to 40 DEG C of stirring reactions 30 minutes；After cooling, add 3,4, 5-trimethoxy bromobenzyl (104.0mg, 0.4mmol), oil bath is heated to 40 DEG C of stirring reactions 2 hours；Add in reactant mixture Enter 20mL water, then extract in three times with 50mL methyl tertiary butyl ether(MTBE), merge organic layer, the lower recycling design of decompression, obtain 3,4-bis- Phenyl-1-(3,4,5-trimethoxy benzyl)-1H-pyrroles-2,5-diketone, it is directly used in follow-up hydrolysis.
(3) hydrolysis: by above-mentioned 3,4-diphenyl-1-(3,4,5-trimethoxy benzyl)-1H-pyrrole-2,5-diones with KOH(268.8 mg, 4.8mmol), water (2.0mL), ethanol (1.0mL) add in reaction bulb, and it is anti-that oil bath is heated to 80 DEG C of stirrings Answer 20 hours；After cooling, dripping 18% hydrochloric acid and being adjusted to pH value is 5.0, and vibration, to solid-liquid two phase stratification, filters to obtain solid, and with 3% hydrochloric acid of 3mL washs solid at twice, after solid drying constant weight, obtains raw material 3,4-diphenyl furan-2,5-diketone (96.2mg), the response rate is 96%；Filtrate mixes with pickle, drips 50%KOH aqueous solution and be adjusted to pH value and be in mixed liquor 11.0, extract three times with 50mL methyl tertiary butyl ether(MTBE), merge organic layer, add anhydrous magnesium sulfate and be dried；It is filtered to remove desiccant After anhydrous magnesium sulfate, being passed through dry HCl gas, have white fluffy solid to separate out in filtrate, sucking filtration obtains white solid, solid After drying constant weight, obtaining 3,4,5-trimethoxy benzylamine hydrochlorides (78.5mg), product yield is that 84%(is with raw material 3,4,5- Trimethoxy bromobenzyl meter).
The preparation method-3 of embodiment 8. 3,4,5-trimethoxy benzylamine (02)
(1) imidizate: by 3,4-bis-(naphthalene-2-base) furan-2,5-diketone (140.0mg, 0.4mmol) and Methanamide (2.7g, 60.0mmol) joins in 10mL microwave reaction pipe, sets the power of microwave reactor as 60W, micro-at 100 DEG C Wave radiation is reacted 4 minutes；After cooling, add water (10mL), use 20mL methyl tertiary butyl ether(MTBE) to be extracted twice, merge organic Layer, adds anhydrous sodium sulfate and is dried, the lower recycling design of decompression, obtains 3,4-bis-(naphthalene-2-base)-1H-pyrroles-2,5-diketone, directly For follow-up N-hydrocarbyl reaction.
(2) N-hydrocarbylation: by above-mentioned 3,4-bis-(naphthalene-2-base)-1H-pyrrole-2,5-diones and EtOK(42.0mg, 0.5mmol), ethanol (8.0mL) add in reaction bulb, in ultrasonic reactor, at 25 DEG C, Ultrasonic Radiation reacts 10 minutes；Subtract After pressure recycling design ethanol, add 10mL acetonitrile and dissolve remaining solid, be transferred in 30 mL microwave reaction pipes, add 3, 4,5-trimethoxy bromobenzyls (104.0mg, 0.4mmol), set the power of microwave reactor as 60W, anti-at 90 DEG C of microwave radiations Answer 10 minutes；Reclaim solvent acetonitrile under decompression, obtain 3,4-bis-(naphthalene-2-base)-1-(3,4,5-trimethoxy benzyl)-1H-pyrrole Cough up-2,5-diketone, it is directly used in follow-up hydrolysis.
3,4-bis-(naphthalene-2-base)-1-(3,4,5-trimethoxy benzyl)-1H-pyrrole-2,5-diones analytical data: ESI-MS: 530(M+H+), 552(M+Na+)。
(3) hydrolysis: by above-mentioned 3,4-bis-(naphthalene-2-base)-1-(3,4,5-trimethoxy benzyl)-1H-pyrroles-2,5-two Ketone and NaOH(160mg, 4.0mmol) and methanol (3.0mL) join in 10mL microwave reaction pipe, set microwave reactor Power was 60W, in 80 DEG C of microwaves 10 minutes；After cooling, dripping 5% hydrochloric acid and being adjusted to pH value is 5.0, and vibration is to biphase point of solid-liquid Layer, filters to obtain solid, and washs solid at twice with 3% hydrochloric acid of 3mL, after solid drying constant weight, obtain raw material 3,4-bis- (naphthalene-2-base) furan-2,5-diketone (133.2mg), the response rate is 95%；Filtrate mixes with pickle, drips in mixed liquor It is 11.0 that 50%KOH aqueous solution is adjusted to pH value, extracts three times with 50mL dichloromethane, merges organic layer, adds anhydrous magnesium sulfate and does Dry；After being filtered to remove desiccant anhydrous magnesium sulfate, vacuum rotary steam recycling design dichloromethane, residue, through column chromatography purification, obtains To 3,4,5-trimethoxy benzylamines (63.0mg), product yield is that 80%(is with raw material 3,4,5-trimethoxy bromobenzyl meters).
The preparation method-4 of embodiment 9. 3,4,5-trimethoxy benzylamine (02)
(1) imidizate: by 3,4-bis-(4-methoxyphenyl) furan-2,5-diketone (124.0mg, 0.4mmol) and 10% NH3Ethanol solution (2.0g, 11.8mmol) join in 10mL microwave reaction pipe, set microwave reactor power For 60W, at 100 DEG C, microwave radiation reacts 20 minutes；Reclaim etoh solvent under decompression, obtain 3,4-bis-(4-methoxyphenyl)- 1H-pyrroles-2,5-diketone, it is directly used in follow-up N-hydrocarbyl reaction.
(2) N-hydrocarbylation: by above-mentioned 3,4-bis-(4-methoxyphenyl)-1H-pyrrole-2,5-diones and Na2CO3 (63.6mg, 0.6mmol) and acetonitrile (8mL), PEG400 (2mL) add in reaction bulb, and air bath is heated to 50 DEG C and stirs Mix reaction 2 hours；After cooling, adding 3,4,5-trimethoxy bromobenzyl (86.4mg, 0.4mmol), air bath is heated to 50 DEG C and stirs Mix reaction 24 hours；Vacuum rotary steam reclaims acetonitrile, then adds 10mL water in reactant mixture, extracts with dichloromethane after 20mL water Take twice, under decompression, reclaim dichloromethane, obtain 3,4-bis-(4-methoxyphenyl)-1-(3,4,5-trimethoxy benzyl)- 1H-pyrroles-2,5-diketone, it is directly used in follow-up hydrolysis.
3,4-bis-(4-methoxyphenyl)-1-(3,4,5-trimethoxy benzyl)-1H-pyrrole-2,5-diones analyzes number According to: ESI-MS:490 (M+H+), 512(M+Na+)。
(3) hydrolysis: by above-mentioned 3,4-bis-(4-methoxyphenyl)-1-(3,4,5-trimethoxy benzyl)-1H-pyrroles-2, 5-diketone and LiOH(240.0mg, 10.0mmol), water (2.0mL), acetonitrile (1.0mL) add in reaction bulb, heating in water bath is extremely 80 DEG C of stirrings are reacted 10 hours；After cooling, dripping 10% sulphuric acid and being adjusted to pH value is 5.0, vibrates to solid-liquid two phase stratification, filters Obtain solid, and wash solid at twice with 5% sulphuric acid of 3mL, after solid drying constant weight, obtain raw material 3,4-bis-(4-methoxyl group Phenyl) furan-2,5-diketone (116.6mg), the response rate is 94%；Filtrate mixes with pickle, drips 10% in mixed liquor It is 10.0 that LiOH aqueous solution is adjusted to pH value, extracts three times with 50mL methyl tertiary butyl ether(MTBE), merges organic layer, adds anhydrous magnesium sulfate It is dried；After being filtered to remove desiccant anhydrous magnesium sulfate, in filtrate, it is passed through dry HBr gas, has white fluffy solid to separate out, Sucking filtration obtains white solid, after solid drying constant weight, obtains 3,4,5-trimethoxies benzylamine hydrobromate (94.5mg), and product is received Rate is that 85%(is in terms of raw material 3,4,5-trimethoxy bromobenzyl).
The preparation method-5 of embodiment 10. 3,4,5-trimethoxy benzylamine (02)
(1) imidizate: by 3,4-bis-(4-methyl naphthalene-2-base) furan-2,5-diketone (151.2mg, 0.4mmol), 5% Ammonia (2.72g, 8.0mmol) joins in 10mL microwave reaction pipe, sets the power of microwave reactor as 60W, at 120 DEG C Lower microwave radiation reacts 6 minutes；After cooling, use 20mL dichloromethane to be extracted twice, merge organic layer, add anhydrous slufuric acid Sodium is dried, and reclaims methylene chloride under decompression, obtains 3,4-bis-(4-methyl naphthalene-2-base)-1H-pyrroles-2, and 5-diketone is directly used In follow-up N-hydrocarbyl reaction.
3,4-bis-(4-methyl naphthalene-2-base)-1H-pyrrole-2,5-diones analytical data: ESI-MS:378 (M+H+), 400 (M+Na+)。
(2) N-hydrocarbylation: by above-mentioned 3,4-bis-(4-methyl naphthalene-2-base)-1H-pyrrole-2,5-diones and EtONa (34.0mg, 0.5mmol), 6mL ethanol join in 10mL microwave reaction pipe, set the power of microwave reactor as 60W, 50 DEG C of microwave radiations react 20 minutes；After decompression lower recovery etoh solvent, add 10mL acetone solution remaining solid, be transferred to 30 In mL microwave reaction pipe, add 3,4,5-trimethoxies benzyl benzenesulfonic acid alcohol ester (135.2mg, 0.4mmol), set microwave The power of reactor is 60W, reacts 30 minutes at 50 DEG C of microwave radiations；Reclaim solvent acetone under decompression, obtain 3,4-bis-(4-first Base naphthalene-2-base)-1-(3,4,5-trimethoxy benzyl)-1H-pyrroles-2,5-diketone, it is directly used in follow-up hydrolysis.
3,4-bis-(4-methyl naphthalene-2-base)-1-(3,4,5-trimethoxy benzyl)-1H-pyrrole-2,5-diones analyzes number According to: ESI-MS:558 (M+H+), 580(M+Na+)。
(3) hydrolysis: by above-mentioned 3,4-bis-(4-methyl naphthalene-2-base)-1-(3,4,5-trimethoxy benzyl)-1H-pyrroles- 2,5-diketone and LiOH(120.0mg, 5.0mmol), water (3.0mL) and methanol (1.0mL) join 10mL microwave reaction pipe In, set the power of microwave reactor as 60W, in 110 DEG C of microwaves 10 minutes；After cooling, drip 10% sulphuric acid and be adjusted to pH value and be 5.0, vibration, to solid-liquid two phase stratification, is filtered to obtain solid, and is washed solid at twice with 5% sulphuric acid of 3mL, and solid drying is permanent After Chong, obtaining raw material 3,4-bis-(4-methyl naphthalene-2-base) furan-2,5-diketone (143.8mg), the response rate is 95%；Filtrate and acid Washing liquid mixes, and dripping 10% LiOH aqueous solution in mixed liquor and being adjusted to pH value is 11.0, extracts three times with 50mL dichloromethane, closes And organic layer, add anhydrous magnesium sulfate and be dried；After being filtered to remove desiccant anhydrous magnesium sulfate, vacuum rotary steam recycling design dichloromethane Alkane, residue, through column chromatography purification, obtains 3,4,5-trimethoxy benzylamines (62.3mg), and product yield is 79%(with raw material 3, and 4, 5-trimethoxy benzyl benzenesulfonic acid alcohol ester meter).
The preparation method-1 of embodiment 11. 4-methoxybenzylamine (03)
(1) imidizate: by 3,4-diphenyl furan-2,5-diketone (100.0mg, 0.4mmol), 1% ammonia (1.4g, 0.8mmol) joining in 10mL microwave reaction pipe, set the power of microwave reactor as 70W, at 120 DEG C, microwave radiation is anti- Answer 5 minutes；After cooling, use 20mL ethyl acetate to be extracted twice, merge organic layer, add anhydrous sodium sulfate and be dried, decompression Lower recovery solvent ethyl acetate, obtains 3,4-diphenyl-1H-pyrroles-2,5-diketone, and yield 100% is directly used in follow-up N-hydrocarbon Glycosylation reaction.
(2) N-hydrocarbylation: by above-mentioned 3,4-diphenyl-1H-pyrrole-2,5-diones and MeOK(35.0mg, 0.5mmol), 6mL ethanol joins in 10mL microwave reaction pipe, sets the power of microwave reactor as 70W, reacts 10 at 90 DEG C of microwave radiations Minute；After decompression lower recovery etoh solvent, add 10mL acetonitrile and dissolve remaining solid, be transferred in 30 mL microwave reaction pipes, then Add 4-methoxyl group benzyl chloride (62.4mg, 0.4mmol), set the power of microwave reactor as 70W, anti-at 90 DEG C of microwave radiations Answer 15 minutes；Reclaim solvent acetonitrile under decompression, obtain 1-(4-methoxy-benzyl)-3,4-diphenyl-1H-pyrroles-2,5-diketone, Yield 99%, is directly used in follow-up hydrolysis.
1-(4-methoxy-benzyl)-3,4-diphenyl-1H-pyrrole-2,5-diones analytical data:1H-NMR(300MHz, CDCl3): δ3.79(3H, s), 4.75(2H, s), 6.86(2H, d, J=8.64), 7.40(12H, m); ESI-MS: 370(M+H+), 392(M+Na+)。
(3) hydrolysis: by above-mentioned 1-(4-methoxy-benzyl)-3,4-diphenyl-1H-pyrrole-2,5-diones and NaOH (120.0mg, 3.0mmol), water (2.0mL) and ethanol (1.0mL) join in 10mL microwave reaction pipe, set microwave reaction The power of device was 70W, in 105 DEG C of microwaves 10 minutes；After cooling, dripping 18% hydrochloric acid and being adjusted to pH value is 5.0, and vibration is to solid-liquid Two phase stratification, filters to obtain solid, and washs solid at twice with 5% hydrochloric acid of 3mL, after solid drying constant weight, obtain raw material 3, 4-diphenyl furan-2,5-diketone (98.6mg), the response rate is 99%；Filtrate mixes with pickle, drips 50% in mixed liquor It is 11.0 that NaOH aqueous solution is adjusted to pH value, extracts three times with 50mL methyl tertiary butyl ether(MTBE), merges organic layer, adds anhydrous magnesium sulfate It is dried；After being filtered to remove desiccant anhydrous magnesium sulfate, in filtrate, it is passed through dry HCl gas, has white fluffy solid to separate out, Sucking filtration obtains white solid, after solid drying constant weight, obtains 4-methoxybenzylamine hydrochloride (59.7mg), and product yield is 86% (in terms of raw material 4-methoxyl group benzyl chloride).
4-methoxybenzylamine (03) analytical data:1H-NMR(300MHz, CDCl3): δ3.80(5H, s), 6.87(2H, d, J=8.53), 7.23(2H, d, J=8.53); ESI-MS: 138(M+H+), 160(M+Na+)。
The preparation method-2 of embodiment 12. 4-methoxybenzylamine (03)
(1) imidizate: by 3,4-diphenyl furan-2,5-diketone (100.0mg, 0.4mmol) and Methanamide (1.8g, 40.0mmol) adding in closed reactor, oil bath is heated to 100 DEG C and reacts 5 hours；After cooling, add the dilution of 10mL water, add Entering 20mL methyl tertiary butyl ether(MTBE) to be extracted twice, merge organic layer, add anhydrous sodium sulfate and be dried, decompression is lower reclaims solvent methyl uncle Butyl ether, obtains 3,4-diphenyl-1H-pyrroles-2, and 5-diketone is directly used in follow-up N-hydrocarbyl reaction.
(2) N-hydrocarbylation: by above-mentioned 3,4-diphenyl-1H-pyrrole-2,5-diones and KHCO3(80.0mg, 0.8mmol), DMF(10.0mL) add in reaction bulb, oil bath is heated to 30 DEG C of stirring reactions 1 hour；After cooling, add 4-first Oxy-benzyl benzenesulfonic acid alcohol ester (111.2mg, 0.4mmol), oil bath is heated to 30 DEG C of stirring reactions 5 hours；To reactant mixture Middle addition 20mL water, then extract in three times with 50mL methyl tertiary butyl ether(MTBE), merge organic layer, the lower recycling design of decompression, obtain 1- (4-methoxy-benzyl)-3,4-diphenyl-1H-pyrroles-2,5-diketone, it is directly used in follow-up hydrolysis.
(3) hydrolysis: by above-mentioned 1-(4-methoxy-benzyl)-3,4-diphenyl-1H-pyrrole-2,5-diones and NaOH (160.0mg, 4.0m mol), water (2.0mL), ethanol (1.0mL) add in reaction bulb, and oil bath is heated to 90 DEG C of stirring reactions 20 hours；After cooling, dripping 18% hydrochloric acid and being adjusted to pH value is 5.0, and vibration, to solid-liquid two phase stratification, filters to obtain solid, and with 5% hydrochloric acid of 3mL washs solid at twice, after solid drying constant weight, obtains raw material 3,4-diphenyl furan-2,5-diketone (95.4mg), the response rate is 95%；Filtrate mixes with pickle, drips 50%KOH aqueous solution and be adjusted to pH value and be in mixed liquor 11.0, extract three times with 50mL methyl tertiary butyl ether(MTBE), merge organic layer, add anhydrous magnesium sulfate and be dried；It is filtered to remove desiccant After anhydrous magnesium sulfate, being passed through dry HCl gas, have white fluffy solid to separate out in filtrate, sucking filtration obtains white solid, solid After drying constant weight, 4-methoxybenzylamine hydrochloride (57.6mg), product yield is that 83%(is with raw material 4-methoxy-benzyl benzene sulphur Acid alcohol ester meter).
The preparation method-3 of embodiment 13. 4-methoxybenzylamine (03)
(1) imidizate: by 3,4-bis-(naphthalene-2-base) furan-2,5-diketone (140.0mg, 0.4mmol) and Methanamide (1.8g, 40.0mmol) joins in 10mL microwave reaction pipe, sets the power of microwave reactor as 70W, micro-at 100 DEG C Wave radiation is reacted 3 minutes；After cooling, add water (10mL), use 20mL methyl tertiary butyl ether(MTBE) to be extracted twice, merge organic Layer, adds anhydrous sodium sulfate and is dried, the lower recycling design of decompression, obtains 3,4-bis-(naphthalene-2-base)-1H-pyrroles-2,5-diketone, directly For follow-up N-hydrocarbyl reaction.
(2) N-hydrocarbylation: by above-mentioned 3,4-bis-(naphthalene-2-base)-1H-pyrrole-2,5-diones and NaOH(24.0mg, 0.6mmol), ethanol (6.0mL) add in reaction bulb, in ultrasonic reactor, at 25 DEG C, Ultrasonic Radiation reacts 20 minutes；Subtract After pressure recycling design ethanol, add 10mL acetonitrile and dissolve remaining solid, be transferred in 30 mL microwave reaction pipes, add 4- Methoxyl group benzyl chloride (62.4mg, 0.4mmol), sets the power of microwave reactor as 70W, reacts 15 points at 90 DEG C of microwave radiations Clock；Reclaim solvent acetonitrile under decompression, obtain 1-(4-methoxy-benzyl)-3,4-bis-(naphthalene-2-base)-1H-pyrroles-2,5-diketone, It is directly used in follow-up hydrolysis.
1-(4-methoxy-benzyl)-3,4-two (naphthalene-2-base)-1H-pyrrole-2,5-diones analytical data: ESI-MS: 470(M+H+), 492(M+Na+)。
(3) hydrolysis: by above-mentioned 1-(4-methoxy-benzyl)-3,4-two (naphthalene-2-base)-1H-pyrrole-2,5-diones and NaOH (160mg, 4.0mmol) and methanol (3.0mL) join in 10mL microwave reaction pipe, set the power of microwave reactor as 70W, in 80 DEG C of microwaves 10 minutes；After cooling, dripping 10% hydrochloric acid and being adjusted to pH value is 5.0, and vibration is to solid-liquid two phase stratification, mistake Filter to obtain solid, and wash solid at twice with 5% hydrochloric acid of 2mL, after solid drying constant weight, obtain raw material 3,4-bis-(naphthalene-2- Base) furan-2,5-diketone (134.6mg), the response rate is 96%；Filtrate mixes with pickle, drips 50%NaOH in mixed liquor It is 11.0 that aqueous solution is adjusted to pH value, extracts three times with 50mL methyl tertiary butyl ether(MTBE), merges organic layer, adds anhydrous sodium sulfate and does Dry；After being filtered to remove desiccant anhydrous sodium sulfate, under decompression, reclaim solvent methyl t-butyl ether, residue through column chromatography purification, Obtaining 4-methoxybenzylamine (43.8mg), product yield is that 80%(is in terms of raw material 4-methoxyl group benzyl chloride).
The preparation method-1 of embodiment 14. 2-fluoro benzylamine (04)
(1) imidizate: by 3,4-diphenyl furan-2,5-diketone (100.0mg, 0.4mmol), 1% ammonia (3.4g, 2.0mmol) joining in 10mL microwave reaction pipe, set the power of microwave reactor as 80W, at 120 DEG C, microwave radiation is anti- Answer 5 minutes；After cooling, use 20mL ethyl acetate to be extracted twice, merge organic layer, add anhydrous sodium sulfate and be dried, decompression Lower recovery solvent ethyl acetate, obtains 3,4-diphenyl-1H-pyrroles-2,5-diketone, and yield 100% is directly used in follow-up N-hydrocarbon Glycosylation reaction.
(2) N-hydrocarbylation: by above-mentioned 3,4-diphenyl-1H-pyrrole-2,5-diones and t-BuOK(56.1mg, 0.5mmol), 8mL ethanol join in 10mL microwave reaction pipe, set the power of microwave reactor as 80W, at 90 DEG C of microwave spokes Penetrate reaction 20 minutes；After decompression lower recovery etoh solvent, add 10mL acetonitrile and dissolve remaining solid, be transferred to 30 mL microwaves anti- Ying Guanzhong, adds 2-fluoro benzyl chloride (57.6mg, 0.4mmol), sets the power of microwave reactor as 80W, at 90 DEG C of microwaves Radioreaction 15 minutes；Reclaim solvent acetonitrile under decompression, obtain 1-(2-Fluoro-benz rLl)-3,4-diphenyl-1H-pyrroles-2,5- Diketone, yield 99%, it is directly used in follow-up hydrolysis.
1-(2-Fluoro-benz rLl)-3,4-diphenyl-1H-pyrrole-2,5-diones analytical data:1H-NMR(300MHz, CDCl3): δ4.90(2H, s), 7.08(2H, m), 7.39(12H, m); ESI-MS: 358(M+H+), 380(M+Na+)。
(3) hydrolysis: by above-mentioned 1-(2-Fluoro-benz rLl)-3,4-diphenyl-1H-pyrrole-2,5-diones and NaOH (120.0mg, 3.0mmol), water (2.0mL) and ethanol (1.0mL) join in 10mL microwave reaction pipe, set microwave reaction The power of device was 80W, in 105 DEG C of microwaves 7 minutes；After cooling, dripping 18% hydrochloric acid and being adjusted to pH value is 5.0, and vibration is to solid-liquid two It is layered mutually, filters to obtain solid, and wash solid at twice with 5% hydrochloric acid of 2mL, after solid drying constant weight, obtain raw material 3,4- Diphenyl furan-2,5-diketone (98.2mg), the response rate is 98%；Filtrate mixes with pickle, drips 50% in mixed liquor It is 11.0 that NaOH aqueous solution is adjusted to pH value, extracts three times with 50mL methyl tertiary butyl ether(MTBE), merges organic layer, adds anhydrous magnesium sulfate It is dried；After being filtered to remove desiccant anhydrous magnesium sulfate, in filtrate, it is passed through dry HCl gas, has white fluffy solid to separate out, Sucking filtration obtains white solid, after solid drying constant weight, obtains 2-fluoro benzylamine hydrochloride (56.2mg), product yield be 87%(with Raw material 2-fluoro benzyl chloride meter).
2-fluoro benzylamine (04) analytical data: 1H-NMR(300MHz, CDCl3): δ3.90(2H, s), 7.03(1H, m), 7.10(1H, m), 7.22(1H, m), 7.32(1H, m); ESI-MS: 126(M+H+), 148(M+Na+)。
The preparation method-2 of embodiment 15. 2-fluoro benzylamine (04)
(1) imidizate: by 3,4-diphenyl furan-2,5-diketone (100.0mg, 0.4mmol) and Methanamide (1.8g, 40.0mmol) adding in closed reactor, oil bath is heated to 100 DEG C and reacts 5 hours；After cooling, add the dilution of 10mL water, add Entering 20mL methyl tertiary butyl ether(MTBE) to be extracted twice, merge organic layer, add anhydrous sodium sulfate and be dried, decompression is lower reclaims solvent methyl uncle Butyl ether, obtains 3,4-diphenyl-1H-pyrroles-2, and 5-diketone is directly used in follow-up N-hydrocarbyl reaction.
(2) N-hydrocarbylation: by above-mentioned 3,4-diphenyl-1H-pyrrole-2,5-diones and NaHCO3(100.8mg, 1.2mmol), DMF(10.0mL) add in reaction bulb, oil bath is heated to 30 DEG C of stirring reactions 1 hour；After cooling, add 2-fluorine For benzyl chloride (57.6mg, 0.4mmol), oil bath is heated to 30 DEG C of stirring reactions 4 hours；20mL water is added in reactant mixture, Extract in three times with 50mL methyl tertiary butyl ether(MTBE) again, merge organic layer, the lower recycling design of decompression, obtain 1-(2-Fluoro-benz rLl)- 3,4-diphenyl-1H-pyrroles-2,5-diketone, it is directly used in follow-up hydrolysis.
(3) hydrolysis: by above-mentioned 1-(2-Fluoro-benz rLl)-3,4-diphenyl-1H-pyrrole-2,5-diones and LiOH (96.0mg, 4.0m mol), water (3.0mL), methanol (1.5mL) add in reaction bulb, and oil bath is heated to 80 DEG C of stirring reactions 24 Hour；After cooling, dripping 18% hydrochloric acid and being adjusted to pH value is 3.0, and vibration, to solid-liquid two phase stratification, filters to obtain solid, and with 3mL 5% hydrochloric acid wash solid at twice, after solid drying constant weight, obtain raw material 3,4-diphenyl furan-2,5-diketone (95.7mg), the response rate is 96%；Filtrate mixes with pickle, drips 10%LiOH aqueous solution and be adjusted to pH value and be in mixed liquor 11.0, extract three times with 50mL methyl tertiary butyl ether(MTBE), merge organic layer, add anhydrous magnesium sulfate and be dried；It is filtered to remove desiccant After anhydrous magnesium sulfate, being passed through dry HBr gas, have white fluffy solid to separate out in filtrate, sucking filtration obtains white solid, solid After drying constant weight, 2-fluoro benzylamine hydrobromate (66.7mg), product yield is that 81%(is in terms of raw material 2-fluoro benzyl chloride).
The preparation method-3 of embodiment 16. 2-fluoro benzylamine (04)
(1) imidizate: by 3,4-bis-(naphthalene-2-base) furan-2,5-diketone (140.0mg, 0.4mmol) and Methanamide (1.8g, 40.0mmol) joins in 10mL microwave reaction pipe, sets the power of microwave reactor as 80W, micro-at 100 DEG C Wave radiation is reacted 4 minutes；After cooling, add water (10mL), use 20mL methyl tertiary butyl ether(MTBE) to be extracted twice, merge organic Layer, adds anhydrous sodium sulfate and is dried, the lower recycling design of decompression, obtains 3,4-bis-(naphthalene-2-base)-1H-pyrroles-2,5-diketone, directly For follow-up N-hydrocarbyl reaction.
(2) N-hydrocarbylation: by above-mentioned 3,4-bis-(naphthalene-2-base)-1H-pyrrole-2,5-diones and t-BuONa(57.6mg, 0.6mmol), ethanol (6.0mL) add in reaction bulb, in ultrasonic reactor, at 25 DEG C, Ultrasonic Radiation reacts 30 minutes；Subtract After pressure recycling design ethanol, add 10mL acetonitrile and dissolve remaining solid, be transferred in 30 mL microwave reaction pipes, add 2- Fluoro benzyl chloride (57.6mg, 0.4mmol), sets the power of microwave reactor as 80W, reacts 15 minutes at 90 DEG C of microwave radiations； Reclaim solvent acetonitrile under decompression, obtain 1-(2-Fluoro-benz rLl)-3,4-bis-(naphthalene-2-base)-1H-pyrroles-2,5-diketone, directly use In follow-up hydrolysis.
1-(2-Fluoro-benz rLl)-3,4-two (naphthalene-2-base)-1H-pyrrole-2,5-diones analytical data: ESI-MS:458 (M+H+), 480(M+Na+)。
(3) hydrolysis: by above-mentioned 1-(2-Fluoro-benz rLl)-3,4-two (naphthalene-2-base)-1H-pyrrole-2,5-diones and NaOH (160mg, 4.0mmol) and ethanol (3.0mL) join in 10mL microwave reaction pipe, set the power of microwave reactor as 80W, in 85 DEG C of microwaves 15 minutes；After cooling, dripping 3% hydrochloric acid and being adjusted to pH value is 4.0, vibrates to solid-liquid two phase stratification, filters Obtain solid, and wash solid at twice with 3% hydrochloric acid of 2mL, after solid drying constant weight, obtain raw material 3,4-bis-(naphthalene-2-base) Furan-2,5-diketone (133.2mg), the response rate is 95%；Filtrate mixes with pickle, drips 50%NaOH water-soluble in mixed liquor It is 11.0 that liquid is adjusted to pH value, extracts three times with 50mL methyl tertiary butyl ether(MTBE), merges organic layer, adds anhydrous sodium sulfate and is dried；Cross After filtering desiccant anhydrous sodium sulfate, reclaiming solvent methyl t-butyl ether under decompression, residue, through column chromatography purification, obtains 2- Fluoro benzylamine (38.5mg), product yield is that 77%(is in terms of raw material 2-fluoro benzyl chloride).
The preparation method-1 of embodiment 17. 4-fluoro benzylamine (05)
(1) imidizate: by 3,4-diphenyl furan-2,5-diketone (100.0mg, 0.4mmol), 10% ammonia (1.7g, 10.0mmol) joining in 10mL microwave reaction pipe, set the power of microwave reactor as 90W, at 120 DEG C, microwave radiation is anti- Answer 4 minutes；After cooling, use 20mL ethyl acetate to be extracted twice, merge organic layer, add anhydrous sodium sulfate and be dried, decompression Lower recovery solvent ethyl acetate, obtains 3,4-diphenyl-1H-pyrroles-2,5-diketone, and yield 100% is directly used in follow-up N-hydrocarbon Glycosylation reaction.
(2) N-hydrocarbylation: by above-mentioned 3,4-diphenyl-1H-pyrrole-2,5-diones and KOH(33.6mg, 0.6mmol), 10mL ethanol joins in 10mL microwave reaction pipe, sets the power of microwave reactor as 90W, reacts 10 at 90 DEG C of microwave radiations Minute；After decompression lower recovery etoh solvent, add 10mL acetonitrile and dissolve remaining solid, be transferred in 30 mL microwave reaction pipes, then Add 4-fluoro benzyl chloride (57.6mg, 0.4mmol), sets the power of microwave reactor as 90W, 90 DEG C of microwave radiations reactions 15 minutes；Reclaim solvent acetonitrile under decompression, obtain 1-(4-Fluoro-benz rLl)-3,4-diphenyl-1H-pyrroles-2,5-diketone, yield 99%, it is directly used in follow-up hydrolysis.
1-(4-Fluoro-benz rLl)-3,4-diphenyl-1H-pyrrole-2,5-diones analytical data:1H-NMR(300MHz, CDCl3): δ4.77(2H, s), 7.01(2H, t, J=8.64), 7.39(12H, m); ESI-MS: 358(M+H+), 380(M+Na+)。
(3) hydrolysis: by above-mentioned 1-(4-Fluoro-benz rLl)-3,4-diphenyl-1H-pyrrole-2,5-diones and NaOH (120.0mg, 3.0mmol), water (2.0mL) and ethanol (1.0mL) join in 10mL microwave reaction pipe, set microwave reaction The power of device was 90W, in 105 DEG C of microwaves 8 minutes；After cooling, dripping 18% hydrochloric acid and being adjusted to pH value is 5.0, and vibration is to solid-liquid two It is layered mutually, filters to obtain solid, and wash solid at twice with 5% hydrochloric acid of 3mL, after solid drying constant weight, obtain raw material 3,4- Diphenyl furan-2,5-diketone (98.0mg), the response rate is 98%；Filtrate mixes with pickle, drips 50% in mixed liquor It is 11.0 that NaOH aqueous solution is adjusted to pH value, extracts three times with 50mL methyl tertiary butyl ether(MTBE), merges organic layer, adds anhydrous sodium sulfate It is dried；After being filtered to remove desiccant anhydrous sodium sulfate, in filtrate, it is passed through dry HCl gas, has white fluffy solid to separate out, Sucking filtration obtains white solid, after solid drying constant weight, obtains 4-fluoro benzylamine hydrochloride (54.9mg), product yield be 85%(with Raw material 4-fluoro benzyl chloride meter).
4-fluoro benzylamine (05) analytical data: 1H-NMR(300MHz, CDCl3): δ3.85(2H, s), 7.01(2H, t, J=8.53), 7.28(2H, t, J=8.53); ESI-MS: 126(M+H+), 148(M+Na+)。
The preparation method-2 of embodiment 18. 4-fluoro benzylamine (05)
(1) imidizate: by 3,4-bis-(4-tolyl) furan-2,5-diketone (111.2mg, 0.4mmol) and 10% NH3Ethanol solution (2.0g, 11.8mmol) join in 10mL microwave reaction pipe, set the power of microwave reactor as 90W, at 100 DEG C, microwave radiation reacts 20 minutes；Reclaim etoh solvent under decompression, obtain 3,4-bis-(4-tolyl)-1H-pyrrole Cough up-2,5-diketone, it is directly used in follow-up N-hydrocarbyl reaction.
(2) N-hydrocarbylation: by above-mentioned 3,4-bis-(4-tolyl)-1H-pyrrole-2,5-diones and Na2CO3(63.6mg, 0.6mmol) and acetonitrile (8mL), PEG400 (2mL) add in 30mL microwave reaction pipe, the power of microwave reactor is set For 90W, at 90 DEG C, microwave radiation reacts 20 minutes；After cooling, add 4-fluoro benzyl chloride (57.6mg, 0.4mmol), set The power of microwave reactor is 90W, and at 90 DEG C, microwave radiation reacts 30 minutes；Vacuum rotary steam reclaims acetonitrile, more mixed to reaction Compound adds 10mL water, is extracted twice with dichloromethane after 20mL water, under decompression, reclaims dichloromethane, obtain 1-(4-fluoro Benzyl)-3,4-bis-(4-tolyl)-1H-pyrroles-2,5-diketone, it is directly used in follow-up hydrolysis.
1-(4-Fluoro-benz rLl)-3,4-two (4-tolyl)-1H-pyrrole-2,5-diones analytical data: ESI-MS: 386(M+H+), 408(M+Na+)。
(3) hydrolysis: by above-mentioned 1-(4-Fluoro-benz rLl)-3,4-two (4-tolyl)-1H-pyrrole-2,5-diones and LiOH (240.0mg, 10.0mmol), water (2.0mL), acetonitrile (1.0mL) add in reaction bulb, heating in water bath to 80 DEG C stirring reaction 10 hours；After cooling, dripping 10% sulphuric acid and being adjusted to pH value is 5.0, and vibration, to solid-liquid two phase stratification, filters to obtain solid, and with 5% sulphuric acid of 3mL washs solid at twice, after solid drying constant weight, obtains raw material 3,4-bis-(4-tolyl) furan-2,5- Diketone (106.8mg), the response rate is 96%；Filtrate mixes with pickle, drips 10% LiOH aqueous solution and be adjusted to pH in mixed liquor Value is 10.0, extracts three times with 50mL methyl tertiary butyl ether(MTBE), merges organic layer, adds anhydrous magnesium sulfate and is dried；It is filtered to remove dry After drying prescription anhydrous magnesium sulfate, being passed through dry HCl gas, have white fluffy solid to separate out in filtrate, sucking filtration obtains white solid, After solid drying constant weight, obtaining 4-fluoro benzylamine hydrochloride (52.3mg), product yield is that 81%(is with raw material 4-fluoro benzyl chloride Meter).
The preparation method-3 of embodiment 19. 4-fluoro benzylamine (05)
(1) imidizate: by 3,4-bis-(naphthalene-2-base) furan-2,5-diketone (140.0mg, 0.4mmol) and Methanamide (1.8g, 40.0mmol) joins in 10mL microwave reaction pipe, sets the power of microwave reactor as 90W, micro-at 100 DEG C Wave radiation is reacted 4 minutes；After cooling, add water (10mL), use 20mL methyl tertiary butyl ether(MTBE) to be extracted twice, merge organic Layer, adds anhydrous sodium sulfate and is dried, the lower recycling design of decompression, obtains 3,4-bis-(naphthalene-2-base)-1H-pyrroles-2,5-diketone, directly For follow-up N-hydrocarbyl reaction.
(2) N-hydrocarbylation: by above-mentioned 3,4-bis-(naphthalene-2-base)-1H-pyrrole-2,5-diones and t-BuONa(57.6mg, 0.6mmol), ethanol (6.0mL) add in reaction bulb, in ultrasonic reactor, at 25 DEG C, Ultrasonic Radiation reacts 30 minutes；Subtract After pressure recycling design ethanol, add 10mL acetonitrile and dissolve remaining solid, be transferred in 30 mL microwave reaction pipes, add 4- Fluoro benzyl chloride (57.6mg, 0.4mmol), sets the power of microwave reactor as 90W, reacts 15 minutes at 90 DEG C of microwave radiations； Reclaim solvent acetonitrile under decompression, obtain 1-(4-Fluoro-benz rLl)-3,4-bis-(naphthalene-2-base)-1H-pyrroles-2,5-diketone, directly use In follow-up hydrolysis.
1-(4-Fluoro-benz rLl)-3,4-two (naphthalene-2-base)-1H-pyrrole-2,5-diones analytical data: ESI-MS:458 (M+H+), 480(M+Na+)。
(3) hydrolysis: by above-mentioned 1-(4-Fluoro-benz rLl)-3,4-two (naphthalene-2-base)-1H-pyrrole-2,5-diones and NaOH (160mg, 4.0mmol) and ethanol (3.0mL) join in 10mL microwave reaction pipe, set the power of microwave reactor as 90W, in 85 DEG C of microwaves 12 minutes；After cooling, dripping 3% hydrochloric acid and being adjusted to pH value is 4.0, vibrates to solid-liquid two phase stratification, filters Obtain solid, and wash solid at twice with 3% hydrochloric acid of 3mL, after solid drying constant weight, obtain raw material 3,4-bis-(naphthalene-2-base) Furan-2,5-diketone (135.8mg), the response rate is 97%；Filtrate mixes with pickle, drips 50%NaOH water-soluble in mixed liquor It is 11.0 that liquid is adjusted to pH value, extracts three times with 50mL methyl tertiary butyl ether(MTBE), merges organic layer, adds anhydrous sodium sulfate and is dried；Cross After filtering desiccant anhydrous sodium sulfate, reclaiming solvent methyl t-butyl ether under decompression, residue, through column chromatography purification, obtains 4- Fluoro benzylamine (39.0mg), product yield is that 78%(is in terms of raw material 4-fluoro benzyl chloride).
The preparation method-1 of embodiment 20. 4-bromo benzylamine (06)
(1) imidizate: by 3,4-diphenyl furan-2,5-diketone (100.0mg, 0.4mmol), 5% ammonia (2.7g, 8.0mmol) joining in 10mL microwave reaction pipe, set the power of microwave reactor as 100W, at 120 DEG C, microwave radiation is anti- Answer 4 minutes；After cooling, use 20mL dichloromethane to be extracted twice, merge organic layer, add anhydrous sodium sulfate and be dried, decompression Lower recovery methylene chloride, obtains 3,4-diphenyl-1H-pyrroles-2,5-diketone, and yield 100% is directly used in follow-up N-hydrocarbon Glycosylation reaction.
(2) N-hydrocarbylation: by above-mentioned 3,4-diphenyl-1H-pyrrole-2,5-diones and KOH(33.6mg, 0.6mmol), 6mL ethanol joins in 10mL microwave reaction pipe, sets the power of microwave reactor as 100W, reacts 10 at 90 DEG C of microwave radiations Minute；After decompression lower recovery etoh solvent, add 10mL acetonitrile and dissolve remaining solid, be transferred in 30 mL microwave reaction pipes, then Add 4-bromo bromobenzyl (99.2mg, 0.4mmol), sets the power of microwave reactor as 100W, 90 DEG C of microwave radiations reactions 10 minutes；Reclaim solvent acetonitrile under decompression, obtain 1-(4-benzyl bromide)-3,4-diphenyl-1H-pyrroles-2,5-diketone, yield 98%, it is directly used in follow-up hydrolysis.
1-(4-benzyl bromide)-3,4-diphenyl-1H-pyrrole-2,5-diones analytical data:1H-NMR(300MHz, CDCl3): δ4.75(2H, s), 7.34(8H, m), 7.46(6H, m); ESI-MS:418(M+H+), 430(M+Na+)。
(3) hydrolysis: by above-mentioned 1-(4-benzyl bromide)-3,4-diphenyl-1H-pyrrole-2,5-diones and KOH (134.4mg, 2.4mmol), water (2.0mL) and ethanol (1.0mL) join in 10mL microwave reaction pipe, set microwave reaction The power of device was 100W, in 102 DEG C of microwaves 10 minutes；After cooling, dripping 18% hydrochloric acid and being adjusted to pH value is 5.0, and vibration is to solid-liquid Two phase stratification, filters to obtain solid, and washs solid at twice with 3% hydrochloric acid of 3mL, after solid drying constant weight, obtain raw material 3, 4-diphenyl furan-2,5-diketone (96.3mg), the response rate is 96%；Filtrate mixes with pickle, drips 50% in mixed liquor It is 11.0 that KOH aqueous solution is adjusted to pH value, extracts three times with 50mL methyl tertiary butyl ether(MTBE), merges organic layer, adds anhydrous magnesium sulfate It is dried；After being filtered to remove desiccant anhydrous magnesium sulfate, in filtrate, it is passed through dry HCl gas, has white fluffy solid to separate out, Sucking filtration obtains white solid, after solid drying constant weight, obtains 4-bromo benzylamine hydrochloride (83.2mg), product yield be 94%(with Raw material 4-bromo bromobenzyl meter).
4-bromo benzylamine (06) analytical data:1H-NMR(300MHz, (CD3)2SO): δ3.98(2H, s), 7.56 (4H, dd, J=8.46), 8.77(3H, s); ESI-MS:186(M+H+), 208(M+Na+)。
The preparation method-2 of embodiment 21. 4-bromo benzylamine (06)
(1) imidizate: by 3,4-diphenyl furan-2,5-diketone (100.0mg, 0.4mmol) and Methanamide (2.3g, 50.0mmol) adding in closed reactor, oil bath is heated to 110 DEG C and reacts 3 hours；After cooling, add the dilution of 10mL water, add Entering 20mL methyl tertiary butyl ether(MTBE) to be extracted twice, merge organic layer, add anhydrous sodium sulfate and be dried, decompression is lower reclaims solvent methyl uncle Butyl ether, obtains 3,4-diphenyl-1H-pyrroles-2, and 5-diketone is directly used in follow-up N-hydrocarbyl reaction.
(2) N-hydrocarbylation: by above-mentioned 3,4-diphenyl-1H-pyrrole-2,5-diones and LiNH2(13.8mg, 0.6mmol), DMF(10.0mL) add in reaction bulb, oil bath is heated to 40 DEG C of stirring reactions 30 minutes；After cooling, add 4-bromine For bromobenzyl (99.2mg, 0.4mmol), oil bath is heated to 40 DEG C of stirring reactions 3 hours；20mL water is added in reactant mixture, Extract in three times with 50mL methyl tertiary butyl ether(MTBE) again, merge organic layer, the lower recycling design of decompression, obtain 1-(4-benzyl bromide)- 3,4-diphenyl-1H-pyrroles-2,5-diketone, it is directly used in follow-up hydrolysis.
(3) hydrolysis: by above-mentioned 1-(4-benzyl bromide)-3,4-diphenyl-1H-pyrrole-2,5-diones and NaOH (120.0mg, 3.0m mol), water (1.5mL), ethanol (1.5mL) add in reaction bulb, and oil bath is heated to 80 DEG C of stirring reactions 20 hours；After cooling, dripping 5% hydrochloric acid and being adjusted to pH value is 5.0, and vibration, to solid-liquid two phase stratification, filters to obtain solid, and with 3mL 5% hydrochloric acid wash solid at twice, after solid drying constant weight, obtain raw material 3,4-diphenyl furan-2,5-diketone (94.4mg), the response rate is 94%；Filtrate mixes with pickle, drips 20%NaOH aqueous solution and be adjusted to pH value and be in mixed liquor 11.0, extract three times with 50mL methyl tertiary butyl ether(MTBE), merge organic layer, add anhydrous sodium sulfate and be dried；It is filtered to remove desiccant After anhydrous sodium sulfate, the lower recycling design of decompression, residue, through column chromatography purification, obtains 4-bromo benzylamine (61.4mg), and product is received Rate is that 83%(is in terms of raw material 4-bromo bromobenzyl).
The preparation method-1 of embodiment 22. 2-bromo benzylamine (07)
(1) imidizate: by 3,4-diphenyl furan-2,5-diketone (100.0mg, 0.4mmol), 5% ammonia (2.7g, 8.0mmol) joining in 10mL microwave reaction pipe, set the power of microwave reactor as 110W, at 120 DEG C, microwave radiation is anti- Answer 4 minutes；After cooling, use 20mL dichloromethane to be extracted twice, merge organic layer, add anhydrous sodium sulfate and be dried, decompression Lower recovery methylene chloride, obtains 3,4-diphenyl-1H-pyrroles-2,5-diketone, and yield 100% is directly used in follow-up N-hydrocarbon Glycosylation reaction.
(2) N-hydrocarbylation: by above-mentioned 3,4-diphenyl-1H-pyrrole-2,5-diones and NaOH(24.0mg, 0.6mmol), 10mL ethanol joins in 10mL microwave reaction pipe, sets the power of microwave reactor as 110W, reacts at 90 DEG C of microwave radiations 15 minutes；After decompression lower recovery etoh solvent, add 10mL acetonitrile and dissolve remaining solid, be transferred in 30 mL microwave reaction pipes, Add 2-bromo bromobenzyl (99.2mg, 0.4mmol), set the power of microwave reactor as 110W, anti-at 90 DEG C of microwave radiations Answer 15 minutes；Reclaim solvent acetonitrile under decompression, obtain 1-(2-benzyl bromide)-3,4-diphenyl-1H-pyrroles-2,5-diketone, receive Rate 99%, is directly used in follow-up hydrolysis.
1-(2-benzyl bromide)-3,4-diphenyl-1H-pyrrole-2,5-diones analytical data:1H-NMR(300MHz, CDCl3): δ4.95(2H, s), 7.43(14H, m); ESI-MS:418(M+H+), 430(M+Na+)。
(3) hydrolysis: by above-mentioned 1-(2-benzyl bromide)-3,4-diphenyl-1H-pyrrole-2,5-diones and NaOH (100.0mg, 2.5mmol), water (2.0mL) and ethanol (1.5mL) join in 10mL microwave reaction pipe, set microwave reaction The power of device was 110W, in 105 DEG C of microwaves 8 minutes；After cooling, dripping 10% hydrochloric acid and being adjusted to pH value is 5.0, and vibration is to solid-liquid Two phase stratification, filters to obtain solid, and washs solid at twice with 5% hydrochloric acid of 2mL, after solid drying constant weight, obtain raw material 3, 4-diphenyl furan-2,5-diketone (98.7mg), the response rate is 99%；Filtrate mixes with pickle, drips 20% in mixed liquor It is 11.0 that NaOH aqueous solution is adjusted to pH value, extracts three times with 50mL methyl tertiary butyl ether(MTBE), merges organic layer, adds anhydrous magnesium sulfate It is dried；After being filtered to remove desiccant anhydrous magnesium sulfate, in filtrate, it is passed through dry HCl gas, has white fluffy solid to separate out, Sucking filtration obtains white solid, after solid drying constant weight, obtains 2-bromo benzylamine hydrochloride (80.6mg), product yield be 91%(with Raw material 2-bromo bromobenzyl meter).
2-bromo benzylamine (07) analytical data: 1H-NMR(300MHz, CDCl3): δ3.93(2H, s), 7.12(1H, m), 7.29(1H, m), 7.38(1H, m), 7.54(1H, m); ESI-MS:186(M+H+), 208(M+Na+)。
The preparation method-2 of embodiment 23. 2-bromo benzylamine (07)
(1) imidizate: by 3,4-diphenyl furan-2,5-diketone (100.0mg, 0.4mmol) and Methanamide (2.3g, 50.0mmol) adding in closed reactor, oil bath is heated to 110 DEG C and reacts 3 hours；After cooling, add the dilution of 10mL water, add Entering 30mL methyl tertiary butyl ether(MTBE) to be extracted twice, merge organic layer, add anhydrous sodium sulfate and be dried, decompression is lower reclaims solvent methyl uncle Butyl ether, obtains 3,4-diphenyl-1H-pyrroles-2, and 5-diketone is directly used in follow-up N-hydrocarbyl reaction.
(2) N-hydrocarbylation: by above-mentioned 3,4-diphenyl-1H-pyrrole-2,5-diones and KHCO3(100.0mg, 1.0 Mmol), DMF(8.0mL) add in reaction bulb, oil bath is heated to 40 DEG C of stirring reactions 30 minutes；After cooling, add 2-bromo bromine Benzyl (99.2mg, 0.4mmol), oil bath is heated to 40 DEG C of stirring reactions 2.5 hours；20mL water is added in reactant mixture, then Extract in three times with 50mL methyl tertiary butyl ether(MTBE), merge organic layer, the lower recycling design of decompression, obtain 1-(2-benzyl bromide)-3, 4-diphenyl-1H-pyrroles-2,5-diketone, it is directly used in follow-up hydrolysis.
(3) hydrolysis: by above-mentioned 1-(2-benzyl bromide)-3,4-diphenyl-1H-pyrrole-2,5-diones and NaOH (120.0mg, 3.0m mol), water (2.0mL), ethanol (1.5mL) add in reaction bulb, and oil bath is heated to 80 DEG C of stirring reactions 20 hours；After cooling, dripping 10% hydrochloric acid and being adjusted to pH value is 4.0, and vibration, to solid-liquid two phase stratification, filters to obtain solid, and with 5% hydrochloric acid of 3mL washs solid at twice, after solid drying constant weight, obtains raw material 3,4-diphenyl furan-2,5-diketone (94.7mg), the response rate is 95%；Filtrate mixes with pickle, drips 20%NaOH aqueous solution and be adjusted to pH value and be in mixed liquor 11.0, extract three times with 50mL methyl tertiary butyl ether(MTBE), merge organic layer, add anhydrous sodium sulfate and be dried；It is filtered to remove desiccant After anhydrous sodium sulfate, the lower recycling design of decompression, residue, through column chromatography purification, obtains 2-bromo benzylamine (59.2mg), and product is received Rate is that 80%(is in terms of raw material 2-bromo bromobenzyl).
The preparation method-1 of embodiment 24. 2-chloro-benzylamine (08)
(1) imidizate: by 3,4-diphenyl furan-2,5-diketone (100.0mg, 0.4mmol), 1% ammonia (3.4g, 2.0mmol) joining in 10mL microwave reaction pipe, set the power of microwave reactor as 90W, at 120 DEG C, microwave radiation is anti- Answer 5 minutes；After cooling, use 20mL ethyl acetate to be extracted twice, merge organic layer, add anhydrous sodium sulfate and be dried, decompression Lower recovery solvent ethyl acetate, obtains 3,4-diphenyl-1H-pyrroles-2,5-diketone, and yield 100% is directly used in follow-up N-hydrocarbon Glycosylation reaction.
(2) N-hydrocarbylation: by above-mentioned 3,4-diphenyl-1H-pyrrole-2,5-diones and t-BuOK(56.1mg, 0.5mmol), 8mL ethanol join in 10mL microwave reaction pipe, set the power of microwave reactor as 90W, at 90 DEG C of microwave spokes Penetrate reaction 20 minutes；After decompression lower recovery etoh solvent, add 10mL acetonitrile and dissolve remaining solid, be transferred to 30 mL microwaves anti- Ying Guanzhong, adds 2-chloro benzyl chloride (64mg, 0.4mmol), sets the power of microwave reactor as 90W, at 90 DEG C of microwave spokes Penetrate reaction 15 minutes；Reclaim solvent acetonitrile under decompression, obtain 1-(2-chlorobenzyl)-3,4-diphenyl-1H-pyrroles-2,5-bis- Ketone, yield 98%, it is directly used in follow-up hydrolysis.
1-(2-chlorobenzyl)-3,4-diphenyl-1H-pyrrole-2,5-diones analytical data:1H-NMR(300MHz, CDCl3): δ4.97(2H, s), 7.23(2H, m), 7.36(8H, m), 7.50(4H, m); ESI-MS:374(M+H+), 396(M+Na+)。
(3) hydrolysis: by above-mentioned 1-(2-chlorobenzyl)-3,4-diphenyl-1H-pyrrole-2,5-diones and NaOH (120.0mg, 3.0mmol), water (2.0mL) and ethanol (1.0mL) join in 10mL microwave reaction pipe, set microwave reaction The power of device was 90W, in 105 DEG C of microwaves 8 minutes；After cooling, dripping 18% hydrochloric acid and being adjusted to pH value is 5.0, and vibration is to solid-liquid two It is layered mutually, filters to obtain solid, and wash solid at twice with 5% hydrochloric acid of 2mL, after solid drying constant weight, obtain raw material 3,4- Diphenyl furan-2,5-diketone (97.3mg), the response rate is 97%；Filtrate mixes with pickle, drips 50% in mixed liquor It is 11.0 that NaOH aqueous solution is adjusted to pH value, extracts three times with 50mL methyl tertiary butyl ether(MTBE), merges organic layer, adds anhydrous magnesium sulfate It is dried；After being filtered to remove desiccant anhydrous magnesium sulfate, in filtrate, it is passed through dry HCl gas, has white fluffy solid to separate out, Sucking filtration obtains white solid, after solid drying constant weight, obtains 2-chloro-benzylamine hydrochlorate (61.1mg), product yield be 86%(with Raw material 2-chloro benzyl chloride meter).
2-chloro-benzylamine (08) analytical data: 1H-NMR(300MHz, CDCl3): δ3.93(2H, s), 7.21(2H, m), 7.36(2H, m); ESI-MS:142(M+H+), 164(M+Na+)。
The preparation method-2 of embodiment 25. 2-chloro-benzylamine (08)
(1) imidizate: by 3,4-diphenyl furan-2,5-diketone (100mg, 0.4mmol) and Methanamide (2.3g, 50.0mmol) adding in closed reactor, oil bath is heated to 110 DEG C and reacts 3 hours；After cooling, add the dilution of 10mL water, add Entering 30mL methyl tertiary butyl ether(MTBE) to be extracted twice, merge organic layer, add anhydrous sodium sulfate and be dried, decompression is lower reclaims solvent methyl uncle Butyl ether, obtains 3,4-diphenyl-1H-pyrroles-2, and 5-diketone is directly used in follow-up N-hydrocarbyl reaction.
(2) N-hydrocarbylation: by above-mentioned 3,4-diphenyl-1H-pyrrole-2,5-diones and Na2CO3(63.6mg, 0.6mmol) And acetonitrile (8mL), PEG400 (2mL) add in reaction bulb, oil bath is heated to 40 DEG C of stirring reactions 30 minutes；Cold But after, adding 2-chloro benzyl chloride (64.0mg, 0.4mmol), oil bath is heated to 40 DEG C of stirring reactions 5 hours；Vacuum rotary steam reclaims Acetonitrile, then in reactant mixture, add 10mL water, then extract in three times with 30mL methyl tertiary butyl ether(MTBE), merge organic layer, subtract Pressure recycling design, obtains 1-(2-chlorobenzyl)-3,4-diphenyl-1H-pyrroles-2,5-diketone, is directly used in follow-up water Solve reaction.
(3) hydrolysis: by above-mentioned 1-(2-chlorobenzyl)-3,4-diphenyl-1H-pyrrole-2,5-diones and Na2CO3 (212.0mg, 2.0mmol), water (3.0mL), acetonitrile (2.0mL) add in reaction bulb, heating in water bath to 80 DEG C stirring reaction 10 Hour；After cooling, dripping 20% sulphuric acid and being adjusted to pH value is 5.0, and vibration, to solid-liquid two phase stratification, filters to obtain solid, and with 3mL 5% sulphuric acid wash solid at twice, after solid drying constant weight, obtain raw material 3,4-diphenyl furan-2,5-diketone (95.0mg), the response rate is 95%；Filtrate mixes with pickle, drips 10% Na in mixed liquor2CO3Aqueous solution is adjusted to pH value 10.0, extract three times with 60mL methyl tertiary butyl ether(MTBE), merge organic layer, add anhydrous magnesium sulfate and be dried；It is filtered to remove desiccant After anhydrous magnesium sulfate, the lower recycling design of decompression, residue, through column chromatography purification, obtains 2-chloro-benzylamine (45.7mg), and product is received Rate is that 81%(is in terms of raw material 2-chloro benzyl chloride).
The preparation method-1 of embodiment 26. 4-cyano group benzylamine (09)
(1) imidizate: by 3,4-diphenyl furan-2,5-diketone (100.0mg, 0.4mmol), 1% ammonia (2.0g, 1.2mmol) joining in 10mL microwave reaction pipe, set the power of microwave reactor as 120W, at 120 DEG C, microwave radiation is anti- Answer 4 minutes；After cooling, use 20mL dichloromethane to be extracted twice, merge organic layer, add anhydrous sodium sulfate and be dried, decompression Lower recovery methylene chloride, obtains 3,4-diphenyl-1H-pyrroles-2,5-diketone, and yield 100% is directly used in follow-up N-hydrocarbon Glycosylation reaction.
(2) N-hydrocarbylation: by above-mentioned 3,4-diphenyl-1H-pyrrole-2,5-diones and KOH(33.6mg, 0.6mmol), 12mL ethanol joins in 30mL microwave reaction pipe, sets the power of microwave reactor as 120W, reacts at 80 DEG C of microwave radiations 15 minutes；After decompression lower recovery etoh solvent, add 12mL acetonitrile and dissolve remaining solid, be transferred in 30 mL microwave reaction pipes, Add 4-cyano group benzyl chloride (60.4mg, 0.4mmol), set the power of microwave reactor as 120W, anti-at 80 DEG C of microwave radiations Answer 15 minutes；Reclaim solvent acetonitrile under decompression, obtain 1-(4-cyanobenzyls)-3,4-diphenyl-1H-pyrroles-2,5-diketone, receive Rate 98%, is directly used in follow-up hydrolysis.
1-(4-cyanobenzyls)-3,4-diphenyl-1H-pyrrole-2,5-diones analytical data:1H-NMR(300MHz, CDCl3): δ4.85(2H, s), 7.40(10H, m), 7.55(2H, d, J=8.30), 7.64(2H, d, J=8.30); ESI-MS: 365(M+H+), 367(M+Na+)。
(3) hydrolysis: by above-mentioned 1-(4-cyanobenzyls)-3,4-diphenyl-1H-pyrrole-2,5-diones and KOH (134.4mg, 2.4mmol), water (2.0mL) and ethanol (1.0mL) join in 10mL microwave reaction pipe, set microwave reaction The power of device was 120W, in 105 DEG C of microwaves 8 minutes；After cooling, dripping 18% hydrochloric acid and being adjusted to pH value is 5.0, and vibration is to solid-liquid Two phase stratification, filters to obtain solid, and washs solid at twice with 5% hydrochloric acid of 2mL, after solid drying constant weight, obtain raw material 3, 4-diphenyl furan-2,5-diketone (97.2mg), the response rate is 97%；Filtrate mixes with pickle, drips 50% in mixed liquor It is 11.0 that KOH aqueous solution is adjusted to pH value, extracts three times with 50mL methyl tertiary butyl ether(MTBE), merges organic layer, adds anhydrous sodium sulfate It is dried；After being filtered to remove desiccant anhydrous sodium sulfate, in filtrate, it is passed through dry HCl gas, has white fluffy solid to separate out, Sucking filtration obtains white solid, after solid drying constant weight, obtains 4-cyanobenzyamine of derivative hydrochlorate (57.3mg), product yield be 85%(with Raw material 4-cyano group benzyl chloride meter).
4-cyano group benzylamine (09) analytical data: 1H-NMR(300MHz, CDCl3): δ4.85(2H, s), 7.40(10H, m), 7.55(2H, d, J=8.30), 7.64(2H, d, J=8.30); ESI-MS: 365(M+H+), 367(M+Na+)。
The preparation method-2 of embodiment 27. 4-cyano group benzylamine (09)
(1) imidizate: by 3,4-diphenyl furan-2,5-diketone (100.0mg, 0.4mmol) and Methanamide (4.5g, 100.0mmol) adding in closed reactor, oil bath is heated to 110 DEG C and reacts 2 hours；After cooling, add the dilution of 20mL water, Add 40mL methyl tertiary butyl ether(MTBE) to be extracted twice, merge organic layer, add anhydrous sodium sulfate and be dried, under decompression, reclaim solvent methyl Tertbutyl ether, obtains 3,4-diphenyl-1H-pyrroles-2, and 5-diketone is directly used in follow-up N-hydrocarbyl reaction.
(2) N-hydrocarbylation: by above-mentioned 3,4-diphenyl-1H-pyrrole-2,5-diones and Na2CO3(63.6mg, 0.6mmol) And acetonitrile (8mL), PEG400 (2mL) add in reaction bulb, oil bath is heated to 40 DEG C of stirring reactions 30 minutes；Cold But after, adding 4-cyano-benzyl alcohol benzene sulfonate (109.2mg, 0.4mmol), oil bath is heated to 40 DEG C of stirring reactions 2 hours；Subtract Pressure rotation is steamed and is reclaimed acetonitrile, then adds 10mL water in reactant mixture, then extracts in three times with 30mL methyl tertiary butyl ether(MTBE), merges Organic layer, the lower recycling design of decompression, obtain 1-(4-cyanobenzyls)-3,4-diphenyl-1H-pyrroles-2,5-diketone, be directly used in Follow-up hydrolysis.
(3) hydrolysis: by above-mentioned 1-(4-cyanobenzyls)-3,4-diphenyl-1H-pyrrole-2,5-diones and NaOH (120.0mg, 3.0mmol), water (3.0mL), ethanol (1.5mL) add in reaction bulb, heating in water bath to 95 DEG C stirring reaction 8 Hour；After cooling, dripping 20% sulphuric acid and being adjusted to pH value is 5.0, and vibration, to solid-liquid two phase stratification, filters to obtain solid, and with 3mL 5% sulphuric acid washs solid at twice, after solid drying constant weight, obtains raw material 3,4-diphenyl furan-2,5-diketone (94.7mg), the response rate is 95%；Filtrate mixes with pickle, drips 20% NaOH aqueous solution and is adjusted to pH value be in mixed liquor 10.0, extract three times with 60mL methyl tertiary butyl ether(MTBE), merge organic layer, add anhydrous magnesium sulfate and be dried；It is filtered to remove desiccant After anhydrous magnesium sulfate, the lower recycling design of decompression, residue, through column chromatography purification, obtains 4-cyano group benzylamine (40.7mg), and product is received Rate is that 77%(is in terms of raw material 4-cyano-benzyl alcohol benzene sulfonate).
The preparation method-1 of embodiment 28. 4-(benzyloxy) benzylamine (10)
(1) imidizate: by 3,4-diphenyl furan-2,5-diketone (100.0mg, 0.4mmol), 5% ammonia (1.7g, 5.0mmol) joining in 10mL microwave reaction pipe, set the power of microwave reactor as 130W, at 120 DEG C, microwave radiation is anti- Answer 4 minutes；After cooling, use 20mL ethyl acetate to be extracted twice, merge organic layer, add anhydrous sodium sulfate and be dried, decompression Lower recovery solvent ethyl acetate, obtains 3,4-diphenyl-1H-pyrroles-2,5-diketone, and yield 100% is directly used in follow-up N-hydrocarbon Glycosylation reaction.
(2) N-hydrocarbylation: by above-mentioned 3,4-diphenyl-1H-pyrrole-2,5-diones and NaOH(32.0mg, 0.8mmol), 8mL ethanol joins in 10mL microwave reaction pipe, sets the power of microwave reactor as 130W, reacts 20 at 90 DEG C of microwave radiations Minute；After decompression lower recovery etoh solvent, dissolve in three times with 10mL acetonitrile, shift remaining solid to 30 mL microwave reaction pipes In, add 4-(benzyloxy) bromobenzyl (110.4mg, 0.4mmol), set the power of microwave reactor as 130W, micro-at 90 DEG C Wave radiation is reacted 10 minutes；Reclaim solvent acetonitrile under decompression, obtain 1-(4-(benzyloxy) benzyl)-3,4-diphenyl-1H-pyrrole Cough up-2,5-diketone, yield 99%, it is directly used in follow-up hydrolysis.
1-(4-(benzyloxy) benzyl)-3,4-diphenyl-1H-pyrrole-2,5-diones analytical data:1H-NMR(300MHz, CDCl3): δ 4.74 (2H, s), 5.04 (2H, m), 6.93 (2H, d, J=8.47), 7.38 (17H, m); ESI-MS: 446(M+H+), 468 (M+Na+)。
(3) hydrolysis: by above-mentioned 1-(4-(benzyloxy) benzyl)-3,4-diphenyl-1H-pyrrole-2,5-diones and NaOH (120.0mg, 3.0mmol), water (2.0mL) and ethanol (1.0mL) join in 10mL microwave reaction pipe, set microwave reaction The power of device was 130W, in 105 DEG C of microwaves 8 minutes；After cooling, dripping 18% hydrochloric acid and being adjusted to pH value is 5.0, and vibration is to solid-liquid Two phase stratification, filters to obtain solid, and washs solid at twice with 5% hydrochloric acid of 3mL, after solid drying constant weight, obtain raw material 3, 4-diphenyl furan-2,5-diketone (98.8mg), the response rate is 99%；Filtrate mixes with pickle, drips 50% in mixed liquor It is 11.0 that NaOH aqueous solution is adjusted to pH value, extracts three times with 50mL methyl tertiary butyl ether(MTBE), merges organic layer, adds anhydrous magnesium sulfate It is dried；After being filtered to remove desiccant anhydrous magnesium sulfate, in filtrate, it is passed through dry HCl gas, has white fluffy solid to separate out, Sucking filtration obtains white solid, after solid drying constant weight, obtains 4-(benzyloxy) benzylamine hydrochloride (75.8mg), and product yield is 89%(is in terms of raw material 4-(benzyloxy) bromobenzyl).
4-(benzyloxy) benzylamine (10) analytical data: 1H-NMR(300MHz, CDCl3): δ3.81(2H, s), 5.06 (2H, s),6.94(2H ,d, J=8.62), 7.23(2H, d, J=8.62), 7.38(5H, m); ESI-MS: 214(M+ H+), 236(M+Na+)。
The preparation method-2 of embodiment 29. 4-(benzyloxy) benzylamine (10)
(1) imidizate: by 3,4-diphenyl furan-2,5-diketone (100.0mg, 0.4mmol) and Methanamide (2.3g, 50.0mmol) adding in closed reactor, oil bath is heated to 100 DEG C and reacts 5 hours；After cooling, add the dilution of 10mL water, add Entering 20mL methyl tertiary butyl ether(MTBE) to be extracted twice, merge organic layer, add anhydrous sodium sulfate and be dried, decompression is lower reclaims solvent methyl uncle Butyl ether, obtains 3,4-diphenyl-1H-pyrroles-2, and 5-diketone is directly used in follow-up N-hydrocarbyl reaction.
(2) N-hydrocarbylation: by above-mentioned 3,4-diphenyl-1H-pyrrole-2,5-diones and K2CO3(82.8mg, 0.6mmol), DMF(8.0mL) adding in reaction bulb, oil bath is heated to 40 DEG C of stirring reactions 30 minutes；After cooling, add 4-(benzyloxy) benzylalcohol Benzene methanesulfonic acid ester (141.6mg, 0.4mmol), oil bath is heated to 40 DEG C of stirring reactions 2 hours；Add in reactant mixture 20mL water, then extract in three times with 50mL methyl tertiary butyl ether(MTBE), merge organic layer, the lower recycling design of decompression, obtain 1-(4-(benzyl Epoxide) benzyl)-3,4-diphenyl-1H-pyrroles-2,5-diketone, it is directly used in follow-up hydrolysis.
(3) hydrolysis: by above-mentioned 1-(4-(benzyloxy) benzyl)-3,4-diphenyl-1H-pyrrole-2,5-diones and KOH (168.0mg, 3.0m mol), water (2.0mL), ethanol (1.0mL) add in reaction bulb, and oil bath is heated to 90 DEG C of stirring reactions 10 hours；After cooling, dripping 18% hydrochloric acid and being adjusted to pH value is 4.0, and vibration, to solid-liquid two phase stratification, filters to obtain solid, and with 3mL 5% hydrochloric acid washs solid at twice, after solid drying constant weight, obtains raw material 3,4-diphenyl furan-2,5-diketone (96.5mg), the response rate is 97%；Filtrate mixes with pickle, drips 50%KOH aqueous solution and be adjusted to pH value and be in mixed liquor 11.0, extract three times with 50mL methyl tertiary butyl ether(MTBE), merge organic layer, add anhydrous magnesium sulfate and be dried；It is filtered to remove desiccant After anhydrous magnesium sulfate, the lower recycling design of decompression, residue, through column chromatography purification, obtains 4-(benzyloxy) benzylamine (69.0mg), produces Thing yield is that 81%(is in terms of raw material 4-(benzyloxy) benzylalcohol benzene methanesulfonic acid ester).
The preparation method-1 of embodiment 30. 4-chloro-benzylamine (11)
Except for the following differences, remaining is all with embodiment 1 for implementation process
(2) N-hydrocarbylation: add 4-chloro bromobenzyl (81.6mg, 0.4mmol), obtain 1-(4-chlorobenzyl)-3,4-bis- Phenyl-1H-pyrrole-2,5-diones.
1-(4-chlorobenzyl)-3,4-diphenyl-1H-pyrrole-2,5-diones analytical data:1H-NMR(300MHz, CDCl3): δ4.77(2H, s), 7.35(10H, m), 7.46(4H, m); ESI-MS: 374(M+H+), 396(M+Na+)。
(3) hydrolysis: above-mentioned 1-(4-chlorobenzyl)-3,4-diphenyl-1H-pyrroles-2,5-diketone hydrolyzes, obtains raw material 3, 4-diphenyl furan-2,5-diketone (97.8mg), the response rate is 98%；Obtain 4-chloro-benzylamine hydrochlorate (61.8mg), yield 87%.(in terms of raw material 4-chloro bromobenzyl).
4-chloro-benzylamine (11) analytical data: 1H-NMR(300MHz, CDCl3): δ3.84(2H, s), 7.27(4H, m); ESI-MS: 142(M+H+), 164(M+Na+)。
The preparation method-2 of embodiment 31. 4-chloro-benzylamine (11)
Except for the following differences, remaining is all with embodiment 29 for implementation process
(2) N-hydrocarbylation: add 4-chloro benzylalcohol benzene methanesulfonic acid ester (112.8mg, 0.4mmol), obtain 1-(4-chloro Benzyl)-3,4-diphenyl-1H-pyrrole-2,5-diones.
(3) hydrolysis: above-mentioned 1-(4-chlorobenzyl)-3,4-diphenyl-1H-pyrroles-2,5-diketone hydrolyzes, obtains raw material 3, 4-diphenyl furan-2,5-diketone (97.4mg), the response rate is 97%；Obtain 4-chloro-benzylamine (45.1mg), yield 80%.(with Raw material 4-chloro benzylalcohol benzene methanesulfonic acid ester meter).
The preparation method-1 of embodiment 32. 3-fluoro benzylamine (12)
Except for the following differences, remaining is all with embodiment 6 for implementation process
(2) N-hydrocarbylation: add 3-fluoro benzyl chloride (57.6mg, 0.4mmol), obtain 1-(3-Fluoro-benz rLl)-3,4-bis- Phenyl-1H-pyrrole-2,5-diones.
1-(3-Fluoro-benz rLl)-3,4-diphenyl-1H-pyrrole-2,5-diones analytical data:1H-NMR(300MHz, CDCl3): δ4.79(2H, s), 6.98(1H, m), 7.16(1H, m), 7.22(1H, d, J=7.64), 7.33(7H, m), 7.47(4H, m); ESI-MS: 358(M+H+), 380(M+Na+)。
(3) hydrolysis: above-mentioned 1-(3-Fluoro-benz rLl)-3,4-diphenyl-1H-pyrroles-2,5-diketone hydrolyzes, obtains raw material 3, 4-diphenyl furan-2,5-diketone (96.9mg), the response rate is 97%；Obtain 3-fluoro benzylamine hydrochloride (54.9mg), yield 85%.(in terms of raw material 3-fluoro benzyl chloride).
3-fluoro benzylamine (12) analytical data: 1H-NMR(300MHz, CDCl3): δ3.88(2H, s), 6.93(1H, m), 7.06(2H, m), 730(1H, m); ESI-MS: 358(M+H+), 380(M+Na+)。
The preparation method-2 of embodiment 33. 3-fluoro benzylamine (12)
Except for the following differences, remaining is all with embodiment 29 for implementation process
(2) N-hydrocarbylation: add 3-fluoro benzylalcohol benzene methanesulfonic acid ester (106.4mg, 0.4mmol), obtain 1-(3-fluoro Benzyl)-3,4-diphenyl-1H-pyrrole-2,5-diones.
(3) hydrolysis: above-mentioned 1-(3-Fluoro-benz rLl)-3,4-diphenyl-1H-pyrroles-2,5-diketone hydrolyzes, obtains raw material 3, 4-diphenyl furan-2,5-diketone (96.1mg), the response rate is 96%；Obtain 3-fluoro benzylamine (38.5mg), yield 77%.(with Raw material 3-fluoro benzylalcohol benzene methanesulfonic acid ester meter).
The preparation method-1 of embodiment 34. 3-chloro-benzylamine (13)
Except for the following differences, remaining is all with embodiment 11 for implementation process
(2) N-hydrocarbylation: add 3-chloro benzyl chloride (64.0mg, 0.4mmol), obtain 1-(3-chlorobenzyl)-3,4-bis- Phenyl-1H-pyrrole-2,5-diones.
1-(3-chlorobenzyl)-3,4-diphenyl-1H-pyrrole-2,5-diones analytical data:1H-NMR(300MHz, CDCl3): δ4.77(2H, s), 7.38(14H, m); ESI-MS: 374(M+H+), 396(M+Na+)。
(3) hydrolysis: above-mentioned 1-(3-chlorobenzyl)-3,4-diphenyl-1H-pyrroles-2,5-diketone hydrolyzes, obtains raw material 3, 4-diphenyl furan-2,5-diketone (97.0mg), the response rate is 97%；Obtain 3-chloro-benzylamine hydrochlorate (58.9mg), yield 83%.(in terms of raw material 3-chloro benzyl chloride).
3-chloro-benzylamine (13) analytical data: 1H-NMR(300MHz, CDCl3): δ3.93(2H, s), 7.21(2H, m), 7.36(2H, m); ESI-MS: 142(M+H+), 164(M+Na+)。
The preparation method-2 of embodiment 35. 3-chloro-benzylamine (13)
Except for the following differences, remaining is all with embodiment 29 for implementation process
(2) N-hydrocarbylation: add 3-chloro benzylalcohol benzene methanesulfonic acid ester (112.8mg, 0.4mmol), obtain 1-(3-chloro Benzyl)-3,4-diphenyl-1H-pyrrole-2,5-diones.
(3) hydrolysis: above-mentioned 1-(3-chlorobenzyl)-3,4-diphenyl-1H-pyrroles-2,5-diketone hydrolyzes, obtains raw material 3, 4-diphenyl furan-2,5-diketone (94.7mg), the response rate is 95%；Obtain 3-chloro-benzylamine (45.1mg), yield 80%.(with Raw material 3-chloro benzylalcohol benzene methanesulfonic acid ester meter).
The preparation method-1 of embodiment 36. 2,3-dichloro-benzylamine (14)
Except for the following differences, remaining is all with embodiment 1 for implementation process
(2) N-hydrocarbylation: add 2,3-dichloro-benzyl chloride (77.6mg, 0.4mmol), obtain 1-(2,3-dichloro-benzyls Base)-3,4-diphenyl-1H-pyrrole-2,5-diones.
1-(2,3-dichloro-benzyl)-3,4-diphenyl-1H-pyrrole-2,5-diones analytical data:1H-NMR(300MHz, CDCl3): δ4.97(2H, s), 7.19(2H, m), 7.37(7H, m), 7.50(4H, m); ESI-MS: 408(M+H+), 430(M+Na+)。
(3) hydrolysis: above-mentioned 1-(2,3-dichloro-benzyl)-3,4-diphenyl-1H-pyrroles-2,5-diketone hydrolyzes, obtains former Material 3,4-diphenyl furan-2,5-diketone (96.3mg), the response rate is 96%；Obtain 2,3-dichloro-benzylamine hydrochloride (72.8mg), yield 86%.(in terms of raw material 2,3-dichloro-benzyl chloride).
2,3-dichloro-benzylamine (14) analytical data: 1H-NMR(300MHz, CDCl3): δ3.96(2H, s), 7.19 (1H, t, J=7.71), 7.31(1H, m), 7.37(1H, m); ESI-MS: 176(M+H+), 198(M+Na+)。
The preparation method-2 of embodiment 37. 2,3-dichloro-benzylamine (14)
Except for the following differences, remaining is all with embodiment 29 for implementation process
(2) N-hydrocarbylation: add 2,3-dichloro-benzylalcohol benzene methanesulfonic acid ester (126.4mg, 0.4mmol), obtain 1-(2, 3-dichloro-benzyl)-3,4-diphenyl-1H-pyrrole-2,5-diones.
(3) hydrolysis: above-mentioned 1-(2,3-dichloro-benzyl)-3,4-diphenyl-1H-pyrroles-2,5-diketone hydrolyzes, obtains former Material 3,4-diphenyl furan-2,5-diketone (95.2mg), the response rate is 95%；Obtain 2,3-dichloro-benzylamine (58.1mg), yield 83%.(in terms of raw material 2,3-dichloro-benzylalcohol benzene methanesulfonic acid ester).
The preparation method-1 of embodiment 38. 3,4-dichloro-benzylamine (15)
Except for the following differences, remaining is all with embodiment 1 for implementation process
(2) N-hydrocarbylation: add 3,4-dichloro-benzyl chloride (77.6mg, 0.4mmol), obtain 1-(3,4-dichloro-benzyls Base)-3,4-diphenyl-1H-pyrrole-2,5-diones.
1-(3,4-dichloro-benzyl)-3,4-diphenyl-1H-pyrrole-2,5-diones analytical data:1H-NMR(300MHz, CDCl3): δ4.74(2H, s), 7.34(7H, m), 7.47(4H, m), 7.55(1H, d, J=1.99); ESI-MS: 408(M+H+), 430(M+Na+)。
(3) hydrolysis: above-mentioned 1-(3,4-dichloro-benzyl)-3,4-diphenyl-1H-pyrroles-2,5-diketone hydrolyzes, obtains former Material 3,4-diphenyl furan-2,5-diketone (98.8mg), the response rate is 99%；Obtain 3,4-dichloro-benzylamine hydrochloride (71.9mg), yield 85%.(in terms of raw material 3,4-dichloro-benzyl chloride).
3,4-dichloro-benzylamine (15) analytical data: 1H-NMR(300MHz, CDCl3): δ3.84(2H, s), 7.15 (1H, d, J=8.04), 7.39(1H, d, J=8.12), 7.43(1H, s); ESI-MS: 176(M+H+), 198(M+ Na+)。
The preparation method-2 of embodiment 39. 3,4-dichloro-benzylamine (15)
Except for the following differences, remaining is all with embodiment 29 for implementation process
(2) N-hydrocarbylation: add 3,4-dichloro-benzylalcohol benzene methanesulfonic acid ester (126.4mg, 0.4mmol), obtain 1-(3, 4-dichloro-benzyl)-3,4-diphenyl-1H-pyrrole-2,5-diones.
(3) hydrolysis: above-mentioned 1-(3,4-dichloro-benzyl)-3,4-diphenyl-1H-pyrroles-2,5-diketone hydrolyzes, obtains former Material 3,4-diphenyl furan-2,5-diketone (95.7mg), the response rate is 96%；Obtain 3,4-dichloro-benzylamine (56.0mg), yield 80%.(in terms of raw material 3,4-dichloro-benzylalcohol benzene methanesulfonic acid ester).
The preparation method-1 of embodiment 40. 2-phenethylamine (16)
Except for the following differences, remaining is all with embodiment 14 for implementation process
(2) N-hydrocarbylation: add beta-bromine ethylbenzene (73.6mg, 0.4mmol), obtain 1-phenethyl-3,4-diphenyl- 1H-pyrrole-2,5-diones.
1-phenethyl-3,4-diphenyl-1H-pyrrole-2,5-diones analytical data:1H-NMR(300MHz, CDCl3): δ 3.00(2H, t, J=7.47, J=7.97), 7.34(2H, t, J=7.64), 7.23(1H, m) 7.37(14H, m); ESI-MS: 354(M+H+), 376 (M+Na+)。
(3) hydrolysis: above-mentioned 1-phenethyl-3,4-diphenyl-1H-pyrroles-2,5-diketone hydrolyzes, obtains raw material 3,4-hexichol Base furan-2,5-diketone (97.6mg), the response rate is 98%；Obtain 2-phenylethylamine hydrochlorate (56.6mg), yield 90%.(with Raw material beta-bromine ethylbenzene meter).
2-phenylethylamine (16) analytical data: 1H-NMR(300MHz, CDCl3): δ2.97(2H, s), 3.13(2H, s), 5.01(2H, s), 7.24(5H, m); ESI-MS: 122(M+H+), 144(M+Na+)。
The preparation method-2 of embodiment 41. 2-phenethylamine (16)
Except for the following differences, remaining is all with embodiment 29 for implementation process
(2) N-hydrocarbylation: add phenethyl alcohol benzene methanesulfonic acid ester (104.8mg, 0.4mmol), obtain 1-phenethyl-3, 4-diphenyl-1H-pyrrole-2,5-diones.
(3) hydrolysis: above-mentioned 1-phenethyl-3,4-diphenyl-1H-pyrroles-2,5-diketone hydrolyzes, obtains raw material 3,4-hexichol Base furan-2,5-diketone (94.6mg), the response rate is 95%；Obtain 2-phenethylamine (40.1mg), yield 83%.(with benzene feedstock second Base alcohol benzene methanesulfonic acid ester meter).
The preparation method-1 of embodiment 42. 2-(benzyloxy) ethamine (17)
Except for the following differences, remaining is all with embodiment 17 for implementation process
(2) N-hydrocarbylation: add ((2-bromine oxethyl) methyl) benzene (85.6mg, 0.4mmol), obtain 1-(2-benzyloxy Ethyl)-3,4-diphenyl-1H-pyrrole-2,5-diones.
1-(2-Benzyloxyethyl)-3,4-diphenyl-1H-pyrrole-2,5-diones analytical data:1H-NMR(300MHz, CDCl3): δ3.74(2H, t, J=5.81), 3.90(2H, t, J=5.56), 4.57(2H, s), 7.35(11H, m) 7.46(4H, m); ESI-MS: 384(M+H+), 406(M+Na+)。
(3) hydrolysis: above-mentioned 1-(2-Benzyloxyethyl)-3,4-diphenyl-1H-pyrroles-2,5-diketone hydrolyzes, obtains raw material 3,4-diphenyl furan-2,5-diketone (98.7mg), the response rate is 99%；Obtain 2-(benzyloxy) ethylamine hydrochloride (68.2mg), Yield 91%.(in terms of raw material ((2-bromine oxethyl) methyl) benzene).
2-(benzyloxy) ethamine (17) analytical data: 1H-NMR(300MHz, CDCl3): δ2.88(2H, t, J= 5.09), 3.51(2H, t, J=5.18), 4.53(2H, s), 7.31(5H, m); ESI-MS: 152(M+H+), 174 (M+Na+)。
The preparation method-2 of embodiment 43. 2-(benzyloxy) ethamine (17)
Except for the following differences, remaining is all with embodiment 29 for implementation process
(2) N-hydrocarbylation: add ((2-bromine oxethyl) methyl) benzene (85.6mg, 0.4mmol), obtain 1-(2-benzyloxy Ethyl)-3,4-diphenyl-1H-pyrrole-2,5-diones.
(3) hydrolysis: above-mentioned 1-(2-Benzyloxyethyl)-3,4-diphenyl-1H-pyrroles-2,5-diketone hydrolyzes, obtains raw material 3,4-diphenyl furan-2,5-diketone (95.9mg), the response rate is 96%；Obtain 2-(benzyloxy) ethamine (51.3mg), yield 85%.(in terms of raw material ((2-bromine oxethyl) methyl) benzene).
The preparation method-1 of embodiment 44. 3-phenylpropyl-1-amine (18)
Except for the following differences, remaining is all with embodiment 22 for implementation process
(2) N-hydrocarbylation: add the bromo-phenyl-propane of 1-(79.2mg, 0.4mmol), obtain 3,4-diphenyl-1-(3-benzene Propyl group)-1H-pyrrole-2,5-diones.
3,4-diphenyl-1-(3-phenylpropyl)-1H-pyrrole-2,5-diones analytical data:1H-NMR(300MHz, CDCl3): δ2.08(2H, m, J=7.31), 2.72(2H, t, J=7.47), 3.98(2H, t, J=6.98), 7.19 (4H, m), 7.37(11H, m); ESI-MS: 368(M+H+), 390(M+Na+)。
(3) hydrolysis: above-mentioned 3,4-diphenyl-1-(3-phenylpropyl)-1H-pyrroles-2,5-diketone hydrolyzes, obtains raw material 3,4- Diphenyl furan-2,5-diketone (97.3mg), the response rate is 97%；Obtain 3-phenylpropyl-1-amine hydrochlorate (64.5mg), yield 94%.(in terms of the bromo-phenyl-propane of raw material 1-).
3-phenylpropyl-1-amine (18) analytical data: 1H-NMR(300MHz, CDCl3): δ2.05(2H, m), 2.68 (2H, t, J=7.62), 2.94(2H, t, J=7.52), 7.20(5H, m); ESI-MS: 136(M+H+), 160(M+ Na+)。
The preparation method-2 of embodiment 45. 3-phenylpropyl-1-amine (18)
Except for the following differences, remaining is all with embodiment 29 for implementation process
(2) N-hydrocarbylation: add the bromo-phenyl-propane of 1-(79.2mg, 0.4mmol), obtain 3,4-diphenyl-1-(3-benzene Propyl group)-1H-pyrrole-2,5-diones.
(3) hydrolysis: above-mentioned 3,4-diphenyl-1-(3-phenylpropyl)-1H-pyrroles-2,5-diketone hydrolyzes, obtains raw material 3,4- Diphenyl furan-2,5-diketone (96.2mg), the response rate is 96%；Obtain 3-phenylpropyl-1-amine (45.3mg), yield 84%.(with Raw material 1-bromo-phenyl-propane meter).
The preparation method-1 of embodiment 46. 1-(4-(3-aminopropan epoxide) 3-methoxyphenyl) ethanol (19)
Except for the following differences, remaining is all with embodiment 24 for implementation process
(2) N-hydrocarbylation: addition 1-(4-(3-chloro propoxyl group) 3-methoxyphenyl) ethanol (97.6mg, 0.4mmol), obtain 1-(3-(4-(1-hydroxyethyl)-2-methoxyphenyl epoxide) propyl group)-3,4-diphenyl-1H-pyrroles- 2,5-diketone.
1-(3-(4-(1-hydroxyethyl)-2-methoxyphenyl epoxide) propyl group)-3,4-diphenyl-1H-pyrroles-2,5-two Ketone analytical data:1H-NMR(300MHz, CDCl3): δ1.48(3H, d, J=6.55), 2.23(2H, m, J=6.55), 3.81(3H, s), 3.88(2H, t, J=6.71, J=6.79), 4.10(2H, t,J=6.31, J=6.39), 4.83 (1H, q, J=6.39), 6.85(2H, s), 6.92(1H, s), 7.38(10H, m); ESI-MS: 458(M+H+), 470(M+Na+)。
(3) hydrolysis: above-mentioned 1-(3-(4-(1-hydroxyethyl)-2-methoxyphenyl epoxide) propyl group)-3,4-diphenyl- 1H-pyrroles-2,5-diketone hydrolyzes, obtains raw material 3,4-diphenyl furan-2,5-diketone (96.6mg), and the response rate is 97%；Obtain 1-(4-(3-aminopropan epoxide) 3-methoxyphenyl) ethylate hydrochlorate (84.7mg), yield 81%.(with raw material 1-(4-(3-chlorine For propoxyl group) 3-methoxyphenyl) alcohol meter).
1-(4-(3-aminopropan epoxide) 3-methoxyphenyl) ethanol (19) analytical data: 1H-NMR(300MHz, CDCl3): δ1.42(3H, s, J=6.40), 2.07(2H, m), 3.88(5H, m), 4.19(2H, t, J=5.74), 4.35(1H, q, J=6.40), 6.83(3H, m); ESI-MS: 226(M+H+), 248(M+Na+)。
The preparation method-2 of embodiment 47. 1-(4-(3-aminopropan epoxide) 3-methoxyphenyl) ethanol (19)
Except for the following differences, remaining is all with embodiment 29 for implementation process
(2) N-hydrocarbylation: addition 1-(4-(3-chloro propoxyl group) 3-methoxyphenyl) ethanol (97.6mg, 0.4mmol), obtain 1-(3-(4-(1-hydroxyethyl)-2-methoxyphenyl epoxide) propyl group)-3,4-diphenyl-1H-pyrroles- 2,5-diketone.
(3) hydrolysis: above-mentioned 1-(3-(4-(1-hydroxyethyl)-2-methoxyphenyl epoxide) propyl group)-3,4-diphenyl- 1H-pyrroles-2,5-diketone hydrolyzes, obtains raw material 3,4-diphenyl furan-2,5-diketone (93.3mg), and the response rate is 93%；Obtain 1-(4-(3-aminopropan epoxide) 3-methoxyphenyl) ethanol (67.5mg), yield 75%.(with raw material 1-(4-(3-chloro the third oxygen Base) 3-methoxyphenyl) alcohol meter).
The preparation method-1 of embodiment 48. 4-benzene butyl-1-amine (20)
Except for the following differences, remaining is all with embodiment 26 for implementation process
(2) N-hydrocarbylation: add 4-phenyl-1-n-butyl bromide (84.8mg, 0.4mmol), obtain 3,4-diphenyl-1-(4- Benzene butyl)-1H-pyrrole-2,5-diones.
3,4-diphenyl-1-(4-benzene butyl)-1H-pyrrole-2,5-diones analytical data:1H-NMR(300MHz, CDCl3): δ1.70(4H, m), 2.67(2H, t, J=6.94), 3.66(2H, t, J=6.94), 7.32(15H, m); ESI-MS: 382(M+H+), 404(M+Na+)。
(3) hydrolysis: above-mentioned 3,4-diphenyl-1-(4-benzene butyl)-1H-pyrroles-2,5-diketone hydrolyzes, obtains raw material 3,4- Diphenyl furan-2,5-diketone (95.4mg), the response rate is 95%；Obtain 4-benzene butyl-1-amine hydrochlorate (53.4mg), yield 72%.(in terms of raw material 4-phenyl-1-n-butyl bromide).
4-benzene butyl-1-amine (20) analytical data:1H-NMR(300MHz, (CD3)2SO): δ1.60(4H, m), 2.58 (2H, t, J=7.22), 2.75(2H, t, J=7.22), 7.19(3H, m), 7.28(2H, m, J=7.51), 8.20 (3H, m); ESI-MS: 150 (M+H+), 172(M+Na+)。
The preparation method-2 of embodiment 49. 4-benzene butyl-1-amine (20)
Except for the following differences, remaining is all with embodiment 29 for implementation process
(2) N-hydrocarbylation: add 4-phenyl-1-n-butyl bromide (84.8mg, 0.4mmol), obtain 3,4-diphenyl-1-(4- Benzene butyl)-1H-pyrrole-2,5-diones.
(3) hydrolysis: above-mentioned 3,4-diphenyl-1-(4-benzene butyl)-1H-pyrroles-2,5-diketone hydrolyzes, obtains raw material 3,4- Diphenyl furan-2,5-diketone (94.0mg), the response rate is 94%；Obtain 4-benzene butyl-1-amine (36.4mg), yield 61%.(with Raw material 4-phenyl-1-n-butyl bromide meter).
The preparation method-1 of embodiment 50. (E)-3-phenylpropyl-2-alkene-1-amine (21)
Except for the following differences, remaining is all with embodiment 24 for implementation process
(2) N-hydrocarbylation: add (E)-(3-Bromopropyl-1-thiazolinyl) benzene (78.4mg, 0.4mmol), obtain 1-(meat Gui Ji)-3,4-diphenyl-1H-pyrrole-2,5-diones.
1-(cinnamyl)-3,4-diphenyl-1H-pyrrole-2,5-diones analytical data:1H-NMR(300MHz, CDCl3): δ4.41(2H, dd, J=6.60, J=1.07), 6.28(1H, m, J=15.85, J=6.65), 6.69(1H, d, J= 15.89), 7.23(1H, t, J=7.33), 7.30(2H, m), 7.36(8H, m), 7.48(4H, m); ESI-MS: 366(M+H+), 388(M+Na+)。
(3) hydrolysis: above-mentioned 1-(cinnamyl)-3,4-diphenyl-1H-pyrroles-2,5-diketone hydrolyzes, obtains raw material 3,4-bis- Benzofurane-2,5-diketone (96.1mg), the response rate is 96%；Obtain (E)-3-phenylpropyl-2-alkene-1-amine hydrochlorate (60.0mg), yield 84%.(in terms of raw material (E)-(3-Bromopropyl-1-thiazolinyl) benzene).
(E)-3-phenylpropyl-2-alkene-1-amine (21) analytical data:1H-NMR(300MHz, (CD3)2SO): δ3.59(2H, d, J=5.71), 6.35(1H, m, J=16.04, J=5.72), 6.76(1H, d, J=16.04), 7.30(1H, t, J =7.37), 7.37(2H, t, J=7.37), 7.43(2H, d, J=7.37), 8.52(3H, s) ; ESI-MS: 134(M +H+), 156(M+Na+)。
The preparation method-2 of embodiment 51. (E)-3-phenylpropyl-2-alkene-1-amine (21)
Except for the following differences, remaining is all with embodiment 29 for implementation process
(2) N-hydrocarbylation: add (E)-(3-Bromopropyl-1-thiazolinyl) benzene (78.4mg, 0.4mmol), obtain 1- (cinnamyl)-3,4-diphenyl-1H-pyrrole-2,5-diones.
(3) hydrolysis: above-mentioned 1-(cinnamyl)-3,4-diphenyl-1H-pyrroles-2,5-diketone hydrolyzes, obtains raw material 3,4-bis- Benzofurane-2,5-diketone (95.3mg), the response rate is 95%；Obtain (E)-3-phenylpropyl-2-alkene-1-amine (40.9mg), yield 77%.(in terms of raw material (E)-(3-Bromopropyl-1-thiazolinyl) benzene).
The invention is not restricted to examples detailed above.In foregoing condition and range, all can obtain target product.

Claims (14)

1. the method preparing primary amine, it is characterised in that: by 3,4-diaryl furan-2,5-diketone (I) → 3,4-bis-virtue Base-1H-pyrrole-2,5-diones compounds (II) → N-alkyl-3,4-diaryl-1H-pyrrole-2,5-diones (III) three kinds The recycling of material, prepares primary amine with halogenated hydrocarbons or hydrocarbon alcohol sulphonic acid ester, ammonia or Methanamide for raw material, comprises the steps:
(1) imidizate: 3,4-diaryl furan-2,5-diketone (I) and ammonia or formamide, prepared acid imide 3,4-bis- Aryl-1H-pyrrole-2,5-diones (II)；
(2) N-hydrocarbylation: with 3,4-diaryl-1H-pyrroles-2,5-diketone (II) is under the effect of alkali, with halogenated hydrocarbons or alkyl There is N-hydrocarbyl reaction in alcohol sulphonic acid ester, prepares N-alkyl-3,4-diaryl-1H-pyrroles-2,5-diketone (III)；
(3) hydrolysis: N-alkyl-3,4-diaryl-1H-pyrroles-2,5-diketone (III) is prepared primary amine through basic hydrolysis, given birth to simultaneously The 2,3-diaryl maleate become forms inner-acid anhydride 3,4-diaryl furan-2,5-diketone (I) through acid treatment automated closed-loop；Institute 3 obtained, 4-diaryl furan-2,5-diketone (I) is directly used in aforesaid imidizate, N-hydrocarbyl reaction, it is achieved circulation Utilize；
Method the most according to claim 1, it is characterised in that: described aryl Ar1With Ar2The most independent for phenyl, naphthalene Base.
Method the most according to claim 2, it is characterised in that: described phenyl is unsubstituted or is taken by 1-5 substituent group In generation, substituent group is independently selected from following groups: halogen, nitro, amino, N-(C1-C6 alkyl) amino, N, N-bis-(C1-C6 alkane Base) amino, C1-C6 acyl amino, hydroxyl, carboxyl, C1-C6 alkyloxycarbonyl, C1-C6 alkyl nitrone, cyano group, sulfydryl, C1- C6 alkyl, C1-C6 alkoxyl, C1-C6 haloalkyl, C3-C6 cycloalkyl；Described naphthyl includes that 1-substituted naphthyl and 2-replace Naphthyl, naphthyl is unsubstituted or is replaced independently selected from substituents by 1-6: halogen, nitro, amino, N-(C1-C6 alkane Base) monosubstituted amino, N, N-(C1-C6 alkyl) disubstituted amino, C1-C6 acyl amino, hydroxyl, carboxyl, C1-C6 alkyl oxygen carbonyl Base, C1-C6 alkyl nitrone, cyano group, sulfydryl, C1-C6 alkyl, C1-C6 alkoxyl, C1-C6 haloalkyl, C3-C6 cycloalkyl.
Method the most according to claim 3, it is characterised in that: described phenyl is unsubstituted or is taken by 1-2 substituent group In generation, substituent group is independently selected from following groups: halogen, nitro, amino, hydroxyl, cyano group, sulfydryl, C1-C3 alkyl, C1-C3 alcoxyl Base, C1-C3 haloalkyl；Described naphthyl includes 1-substituted naphthyl and 2-substituted naphthyl, and naphthyl is unsubstituted or only by 1-2 On the spot replace selected from substituents: halogen, nitro, amino, hydroxyl, carboxyl, cyano group, sulfydryl, C1-C3 alkyl, C1-C3 alcoxyl Base, C1-C3 haloalkyl.
Method the most according to claim 1, it is characterised in that: the alkali described in described step (2) or (3) selected from KOH, NaOH、LiOH、Ca(OH)2、Ba(OH)2、CsOH、Sr(OH)2、K2CO3、Na2CO3、Li2CO3、KHCO3、NaHCO3、LiHCO3、 LiNH2、t-BuOK、t-BuONa、t-BuOLi、MeOK、EtOK、MeONa、EtONa、MeOLi、EtOLi、LDA、DMAP、 LiHMDS、C4H9Li、C6H5Li；Acid is selected from organic acid and mineral acid, and wherein mineral acid is hydrochloric acid, sulphuric acid, hydrobromic acid, phosphoric acid, nitre Acid, organic acid is formic acid, acetic acid, citric acid, oxalic acid, tartaric acid, benzoic acid, malic acid.
Method the most according to claim 1, it is characterised in that:
The structure of described halogenated hydrocarbons or hydrocarbon alcohol sulphonic acid ester RX is as follows:
Prepared primary amine RNH2Structure as follows:
Wherein, X is selected from halogen or sulfonyloxy, and described halogen is selected from benzene selected from iodine, bromine, chlorine or fluorine, described sulfonyloxy Base sulfonyloxy, tolysulfonyl epoxide, p-nitrophenyl sulfonyloxy, to chloro benzenesulfonyloxy, to methoxybenzene sulfonyloxy, Sulfonyloxy methyl epoxide, fluoromethyl sulfonyloxy, ethylsulfonyloxy or phenethyl sulfonyloxy；
Y1、Y2It is each independently selected from-CR6=CR7-、-C≡C-、-O-、-NR8R9-、-S-、-CO-、-SO-、-SO2-；
Z is selected from hydrogen, phenyl that is unsubstituted or that replaced by 1-5 substituent group, and substituent group is independently selected from following groups: halogen, Nitro, amino, N-(C1-C6 alkyl) monosubstituted amino, N, N-(C1-C6 alkyl) disubstituted amino, C1-C6 acyl amino, hydroxyl Base, carboxyl, C1-C6 alkyloxycarbonyl, C1-C6 alkyl nitrone, cyano group, sulfydryl, C1-C6 alkyl, C1-C6 alkoxyl, C3-C6 Cycloalkyl or wherein said alkyl can be replaced by halogen, hydroxyl, amino；
R1、R2、R3、R4、R5、R6、R7、R8And R9It is each independently selected from hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl；
N, m, p, q are selected from 0,1,2,3.
Method the most according to claim 6, it is characterised in that:
Wherein, wherein, X selected from iodine, bromine, chlorine, fluorine, phenylsulfonyloxy group, tolysulfonyl epoxide, to chloro benzenesulfonyloxy or first Base sulfonyloxy；
Y1、Y2It is each independently selected from-CR6=CR7-、-C≡C-、-O-、-NR8R9-、-S-；
Z is selected from hydrogen, phenyl that is unsubstituted or that replaced by 1-3 substituent group, and substituent group is independently selected from following groups: halogen, Nitro, amino, hydroxyl, carboxyl, C1-C3 alkyloxycarbonyl, C1-C3 alkyl nitrone, cyano group, sulfydryl, C1-C3 alkyl, C1-C3 Alkoxyl, C3-C6 cycloalkyl or wherein said alkyl can be replaced by halogen, hydroxyl, amino；
R1、R2、R3、R4、R5、R6、R7、R8And R9It is each independently selected from hydrogen, C1-C3 alkyl；
N, m, p, q are selected from 0,1,2,3.
Method the most according to claim 1, it is characterised in that: in step (1), 3,4-diaryl furan-2,5-diketone (I) It is 1:1～100 with the mol ratio of ammonia or Methanamide；Described ammonia is with NH3For the solution of solute, the solvent of use selected from water, Any ratio mixture of methanol, ethanol, propanol, the tert-butyl alcohol, isopropanol, sec-butyl alcohol or above-mentioned each solvent, the concentration of ammonia solution Scope is saturated solution～0.1%；Methanamide directly uses, or be configured to solution use, solvent selected from water, methanol, ethanol, third Ketone, dioxane, ethylene glycol, oxolane, DMF, DMSO or any mixture, the concentration range of formamide solution is 100 ～0.1%, range of reaction temperature is 0～150 DEG C.
Method the most according to claim 1, it is characterised in that: in step (2), 3,4-diaryl-1H-pyrroles-2,5-bis- Ketone compounds (II) is 1:1～20 with the mol ratio of alkali；Described alkali is selected from KOH, NaOH, LiOH, Ca (OH)2、K2CO3、 Na2CO3、KHCO3、NaHCO3、t-BuOK、MeONa、EtONa、LDA、DMAP、LiHMDS、C4H9Li、C6H5Li；Solvent is selected from second Any ratio mixture of alcohol, propanol, the tert-butyl alcohol, isopropanol, sec-butyl alcohol, acetonitrile, acetone, DMF and DMSO or above-mentioned each solvent, Compound (II) is 1:1～200 with the mass ratio of solvent, and range of reaction temperature is 0～150 DEG C.
Method the most according to claim 1, it is characterised in that: in step (3), N-alkyl-3,4-diaryl-1H-pyrrole Coughing up-2, the mol ratio of 5-diketone (III) and alkali is 1:2～50, and solvent is selected from water, methanol, ethanol, propanol, the tert-butyl alcohol, isopropyl Any ratio mixture of alcohol, sec-butyl alcohol, ether, acetonitrile, acetone, DMF and DMSO or above-mentioned each solvent, N-alkyl-3,4-bis- Aryl-1H-pyrroles-2,5-diketone (III) is 1:1～200 with the mass ratio of solvent, and range of reaction temperature is 0～150 DEG C.
11. methods described in-10 any one according to Claim 8, it is characterised in that: heating uses conventional heating or microwave to shine Penetrate heating.
12. methods according to claim 11, it is characterised in that: when conventional heating is less than 100 DEG C, use air bath, oil Bath, sand-bath, steam bath, water-bath, the response time is 0.05～24 hour.
13. methods according to claim 1, it is characterised in that: 2 generated in step (3), in 3-diaryl maleate Adding acid, be 4-6 to reacting liquid pH value and have solid to separate out, vibration is layered, and obtains 3,4-diaryl furan-2,5-diketone (I), and 3, 4-diaryl furan-2,5-diketone (I) is directly used in imidizate；Or reactant liquor extracts routinely, distills, separates, produced Thing primary amine；Or reactant liquor becomes salt with acid after extraction, obtains resulting primary amine salt.
14. methods according to claim 13, it is characterised in that: described acid selected from hydrochloric acid, sulphuric acid, hydrobromic acid, formic acid, Acetic acid, citric acid, oxalic acid, the organic solvent that described extraction is used is selected from methyl tertiary butyl ether(MTBE), dichloromethane or acetic acid second Ester.
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