CN102146008B - Organic solvent-free synthesis method of aromatic amine compounds - Google Patents
Organic solvent-free synthesis method of aromatic amine compounds Download PDFInfo
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Abstract
The invention provides an organic solvent-free synthesis method of aromatic amine compounds. In the method, copper powder is used as a catalyst, aryl halide and amine are used to perform Ullmann C-N coupling reaction in an organic solvent-free system to synthetize aromatic amine compounds. Compared with the traditional synthesis methods of aromatic amines, the synthesis method provided by the invention is simple to operate, consumes less catalyst, has the advantages of low cost and high product yield; and strong base and other additives are not required to be added in the reaction system, and the method is suitable for the industrial syntheses of aromatic amine compounds.
Description
Technical field
The invention belongs to the aromatic amine compound technical field, be specifically related to a kind of organic solvent-free synthetic method of aromatic amine compound.
Background technology
Aromatic amine compound is important biologically active substance and organic synthesis intermediate mostly, at aspects such as pharmacy, dyestuff, organic materialss, is widely used.Ullmann C-N linked reaction is by one of important method of aryl halide synthetic aroma amine compound.Traditionally, the low and severe reaction conditions of Ullmann C-N linked reaction synthetic aroma amine productive rate, need high temperature, highly basic, stoichiometric copper catalyst etc., limited its widespread use.In recent years, the report of much improving one's methods is arranged, these methods are generally to adopt the monovalence copper compound as CuI or Cu
2o etc. are catalyzer, add certain part and the organic solvent system of mineral alkali, for example, with the CuI catalyzer, with K
2cO
3for alkali, take amino acid as part and coupling agent in N,N-dimethylacetamide, reacted (J.Am.Chem.Soc.1998,120,12459-12467); For another example, CuI catalysis, add K
2cO
3, Cs
2cO
3or K
2pO
4, 1,10-phenanthroline, picolinic acid, L-PROLINE, CHP, sarcosine or DMG are part, methyl-sulphoxide is made solvent (Org.Lett.2003,5,2453-2455; J.Org.Chem.2005,70,5164-5173; J.Org.Chem.2009,74,4542-4546); In addition, under microwave radiation, CuI or Cu (OAc)
2catalysis, add K
2cO
3, L-PROLINE, glycine, Valine or L-Phe are part, DMF do under solvent condition reaction (Tetrahedron Lett.2009,50,5159-5161).In a word, these are improved one's methods and all carry out in organic solvent, and need to add highly basic and part, and cost is increased, the aftertreatment complexity, and environmental pollution is serious, is unfavorable for industrial production.Recently, the people such as Wolf adopts Cu
2o catalysis, realized the reaction (Chem.Commun.2009,3035-3037) without part, in reaction, with the mixed system of N-Methyl pyrrolidone and water, makes solvent, the consumption of organic solvent reduced, but can't be completely free of organic solvent.This class reaction (Eur.J.Org.Chem.2010,1854-1857) that is reported in copper complex catalysis under pure aquatic system is arranged in the recent period, but still need to use highly basic as NaOH, KOH etc.
Summary of the invention
Technical problem solved by the invention is to overcome the shortcoming of above-mentioned aromatic amine compound synthetic method, and a kind of organic solvent-free synthetic method of simple to operate, environmental pollution is little, catalyst levels is few, product yield is high aromatic amine compound is provided.
The technical scheme that solves the problems of the technologies described above employing is comprised of following step: mixture, copper powder that the mass ratio of the aqueous solution of the amine that is 10%～70% by aryl halide, massfraction or amine and distilled water is 1: 0～2.5 mix, the mol ratio of aryl halide and amine, copper powder is 1: 1～20: 0.03～0.1,80～120 ℃ of stirring reactions 0.3～24 hour, reaction mixture, through extraction, separation, is prepared into aromatic amine compound.
Above-mentioned aryl halide means with formula ArX, in formula, X is any one in I, Br, Cl, Ar is any one in phenyl ring, pyridine ring, naphthalene nucleus, thiphene ring, or the acyl group of the straight or branched alkoxyl group of the straight or branched alkyl of I, the Br of phenyl ring, pyridine ring, naphthalene nucleus, thiphene ring, C1, C1～C12, carboxyl, nitro, C1～C12, C1～C6, any one in the cyano group substituent; The primary amine that amine described in the aqueous solution of the amine that above-mentioned massfraction is 10%～70% is ammonia, C1～C6, the amine described in the mixture that the mass ratio of amine and water is 1: 0～2 is for using formula Y (CH
2)
nthe compound that NHR means, in formula the value of n be 1～12, the Y alkoxyl group that is H, carboxyl, amino, hydroxyl, C1～C6, any one in phenyl, any one in the straight or branched alkyl that R is H, C1～C6.
The aqueous solution, the copper powder of the amine that the present invention is preferably 50%～70% by aryl halide with massfraction mix, and the mol ratio of aryl halide and amine, copper powder is 1: 4～6: 0.05～0.1,100 ℃ stirring reaction 8～24 hours, the primary amine that described amine is C1～C6.
Ammonia soln, copper powder that the present invention is preferably 25%～30% by aryl halide with massfraction mix, and the mol ratio of aryl halide and ammonia, copper powder is 1: 8～12: 0.05～0.1,100 ℃ stirring reaction 6～24 hours.
The mol ratio of preferred aryl groups halogen of the present invention and amine, copper powder is 1: 4～6: 0.05～0.1, and described amine is for using formula Y (CH
2)
nthe compound that NHR means, in formula, the value of n is that 2～4, Y is amino, any one in the straight or branched alkyl that R is H, C1～C6,100 ℃ of stirring reactions 0.3～1 hour.
The mol ratio of preferred aryl groups halogen of the present invention and amine, copper powder is 1: 4～6: 0.05～0.1, and described amine is for using formula Y (CH
2)
nthe compound that NHR means, in formula the value of n be 2～12, the Y alkoxyl group that is H, hydroxyl, C1～C6, any one in phenyl, any one in the straight or branched alkyl that R is H, C1～C6,100 ℃ of stirring reactions 6～24 hours.
The mol ratio of preferred aryl groups halogen of the present invention and amine, copper powder is 1: 1～2: 0.05～0.1, and described amine is for using formula Y (CH
2)
nthe compound that NHR means, in formula, the value of n is that 1, Y is carboxyl, any one in the straight or branched alkyl that R is H, C1～C6,100 ℃ of stirring reactions 10～24 hours.
The present invention is usingd copper powder as catalyzer, and under pure aquatic system, Ullmann C-N linked reaction, synthetic aroma amine compound occur for aryl halide and amine.The present invention compares with existing aromatic amine material synthetic method, and in reaction system, highly basic is added at end, simple to operate, environmental pollution is little, catalyst levels is few, and catalytic reaction activity is high, and production cost is low, and product yield is high, can be used for the synthetic of aromatic amine compound.
Embodiment
Below in conjunction with embodiment, the present invention is described in more detail, but the invention is not restricted to these embodiment.
Embodiment 1
Take and prepare aniline as example, the structural formula of aniline is:
Raw materials used and preparation method thereof be: in the 25mL sealed tube, add the 0.032g copper powder, 1.560g bromobenzene, 7.0mL the ammonia soln that massfraction is 30%, the piston of screwing hermetic pipe, bromobenzene and ammonia, the mol ratio of copper powder is 1: 10: 0.05, sealed tube is placed in to 100 ℃ of oil baths, stirring reaction 18 hours, cooling reaction system, open piston, reacted mixed solution is extracted with ethyl acetate, the organic phase anhydrous sodium sulfate drying, 40～50 ℃ of rotary evaporation to dripless are dripped, separate (sherwood oil: ethyl acetate=5: 1) by column chromatography, be prepared into aniline, its yield is 99.0%.
Products therefrom is characterized with Bruker Avance type superconduction fourier numeralization nuclear magnetic resonance spectrometer, and characterization data is as follows:
1H?NMR(d
6-DMSO，300Hz)δ(ppm)：6.97-7.02(m，2H)，6.48-6.57(m，2H)，4.97(s，2H)。
13C?NMR(75MHz，d
6-DMSO)δ(ppm)：114.4，116.2，129.3，149.0。
Nuclear magnetic data shows that products therefrom is aniline.
The bromobenzene of the present embodiment also available equimolar iodobenzene is replaced.
Embodiment 2
Take and prepare methylphenylamine as example, the structural formula of methylphenylamine is:
Raw materials used and preparation method thereof be: in the 25mL sealed tube, add the 0.032g copper powder, 1.560g bromobenzene, 5.4mL the aqueous methylamine solution that massfraction is 30%, piston on the screwing hermetic pipe, bromobenzene and methylamine, the mol ratio of copper powder is 1: 5: 0.05, sealed tube is placed in to 100 ℃ of oil baths, stirring reaction 12 hours, cooling reaction system, open piston, reacted mixed solution is extracted with ethyl acetate, the organic phase anhydrous sodium sulfate drying, 40～50 ℃ of rotary evaporation to dripless are dripped, separate (sherwood oil: ethyl acetate=5: 1) by column chromatography, be prepared into methylphenylamine, its yield is 99.6%.
Products therefrom is characterized with Bruker Avance type superconduction fourier numeralization nuclear magnetic resonance spectrometer, and characterization data is as follows:
1H?NMR(d
6-DMSO，300Hz)δ(ppm)：2.67(s，3H)，5.55(s，1H)，6.5-6.54(d，J＝5.2Hz，3H)，7.07-7.09(s，2H)。
13C?NMR(75MHz，d
6-DMSO)δ(ppm)：30.1，112.1，115.9，129.2，150.4。
Nuclear magnetic data shows that products therefrom is methylphenylamine.
The bromobenzene of the present embodiment also available equimolar iodobenzene is replaced.
Embodiment 3
Take and prepare N-ethylaniline as example, the structural formula of N-ethylaniline is:
Raw materials used and preparation method thereof be: in the 25mL sealed tube, add the 0.032g copper powder, 1.560g bromobenzene, 4.7mL the ethylamine solution that massfraction is 30%, piston on the screwing hermetic pipe, bromobenzene and ethamine, the mol ratio of copper powder is 1: 5: 0.05, sealed tube is placed in to 100 ℃ of oil baths, stirring reaction 12 hours, cooling reaction system, open piston, reacted mixed solution is extracted with ethyl acetate, the organic phase anhydrous sodium sulfate drying, 40～50 ℃ of rotary evaporation to dripless are dripped, separate (sherwood oil: ethyl acetate=5: 1) by column chromatography, be prepared into N-ethylaniline, its yield is 99.1%.
Products therefrom is characterized with Bruker Avance type superconduction fourier numeralization nuclear magnetic resonance spectrometer, and characterization data is as follows:
1H?NMR(300MHz，d
6-DMSO)δ(ppm)：1.13-1.15(t，J＝2.7Hz，3H)，2.98-3.00(t，J＝3.2Hz，2H)，5.36(s，1H)，6.52-6.53(d，J＝2.7Hz，3H)，7.04(s，1H)。
13C?NMR(75MHz，d
6-DMSO)δ(ppm)：14.8，37.8，112.4，115.9，129.3，149.5。
Nuclear magnetic data shows that products therefrom is N-ethylaniline.
The bromobenzene of the present embodiment also available equimolar iodobenzene is replaced.
Embodiment 4
Take and prepare o-Nitraniline as example, the structural formula of o-Nitraniline is:
Raw materials used and preparation method thereof be: in the 25mL sealed tube, add the 0.032g copper powder, 2.020g adjacent nitro bromobenzene, 7.0mL the ammonia soln that massfraction is 30%, piston on the screwing hermetic pipe, adjacent nitro bromobenzene and ammonia, the mol ratio of copper powder is 1: 10: 0.05, sealed tube is placed in to 100 ℃ of oil baths, stirring reaction 20 hours, cooling reaction system, open piston, reacted mixed solution is extracted with ethyl acetate, the organic phase anhydrous sodium sulfate drying, 40～50 ℃ of rotary evaporation to dripless are dripped, separate (sherwood oil: ethyl acetate=5: 1) by column chromatography, be prepared into o-Nitraniline, its yield is 99.8%.
Products therefrom is characterized with Bruker Avance type superconduction fourier numeralization nuclear magnetic resonance spectrometer, and characterization data is as follows:
1H?NMR(300MHz，d
6-DMSO)δ(ppm)：6.63-6.65(d，J＝7.8Hz，1H)，7.05-7.02(d，J＝8.4Hz，1H)，7.43(s，1H)，7.92-8.03(m，2H)。
13C?NMR(75MHz，d
6-DMSO)δ(ppm)：115.9，119.6，125.8，134.3，136.0，146.6。
Nuclear magnetic data shows that products therefrom is o-Nitraniline.
The adjacent nitro bromobenzene of the present embodiment also available equimolar adjacent nitro iodobenzene is replaced.
Embodiment 5
Take and prepare P-nethoxyaniline as example, the structural formula of P-nethoxyaniline is:
Raw materials used and preparation method thereof be: in the 25mL sealed tube, add the 0.032g copper powder, 1.870g to the methoxyl group bromobenzene, 7.0mL the ammonia soln that massfraction is 30%, piston on the screwing hermetic pipe, to methoxyl group bromobenzene and ammonia, the mol ratio of copper powder is 1: 10: 0.05, sealed tube is placed in to 100 ℃ of oil baths, stirring reaction 20 hours, cooling reaction system, open piston, reacted mixed solution is extracted with ethyl acetate, the organic phase anhydrous sodium sulfate drying, 40～50 ℃ of rotary evaporation to dripless are dripped, separate (sherwood oil: ethyl acetate=5: 1) by column chromatography, be prepared into P-nethoxyaniline, its yield is 98.2%.
Products therefrom is characterized with Bruker Avance type superconduction fourier numeralization nuclear magnetic resonance spectrometer, and characterization data is as follows:
1H?NMR(300MHz，d
6-DMSO)δ(ppm)：3.61(s，3H)，4.58(s，2H)，6.50-6.52(d，J＝8.4Hz，2H)，6.65-6.63(d，J＝7.8Hz，1H)。
13C?NMR(75MHz，d
6-DMSO)δ(ppm)：55.8，115.0，115.5，142.7，151.2。
Nuclear magnetic data shows that products therefrom is P-nethoxyaniline.
The present embodiment to methoxyl group bromobenzene also available equimolar the methoxyl group iodobenzene is replaced.
Embodiment 6
The preparation of take is example to monomethylaniline, to the structural formula of monomethylaniline, is:
Raw materials used and preparation method thereof be: in the 25mL sealed tube, add the 0.032g copper powder, 1.710g to the methyl bromobenzene, 7.0mL the ammonia soln that massfraction is 30%, piston on the screwing hermetic pipe, to methyl bromobenzene and ammonia, the mol ratio of copper powder is 1: 10: 0.05, sealed tube is placed in to 100 ℃ of oil baths, stirring reaction 24 hours, cooling reaction system, open piston, reacted mixed solution is extracted with ethyl acetate, the organic phase anhydrous sodium sulfate drying, 40～50 ℃ of rotary evaporation to dripless are dripped, separate (sherwood oil: ethyl acetate=5: 1) by column chromatography, be prepared into monomethylaniline, its yield is 60.3%.
Products therefrom is characterized with Bruker Avance type superconduction fourier numeralization nuclear magnetic resonance spectrometer, and characterization data is as follows:
1H?NMR(300MHz，d
6-DMSO)δ(ppm)：2.51(s，3H)，6.58-6.61(d，J＝9.0Hz，2H)，6.71(s，2H)，7.93-7.96(d，J＝9.0Hz，2H)。
13C?NMR(75MHz，d
6-DMSO)δ(ppm)：20.6，114.6，124.5，129.7，146.5。
Nuclear magnetic data shows that products therefrom is to monomethylaniline.
The present embodiment to methyl bromobenzene also available equimolar the methyl iodobenzene is replaced.
Embodiment 7
Take and prepare para-aminoacetophenone as example, the structural formula of para-aminoacetophenone is:
Raw materials used and preparation method thereof be: in the 25mL sealed tube, add the 0.032g copper powder, 1.990g parabromoacetophenone, 7.0mL the ammonia soln that massfraction is 30%, piston on the screwing hermetic pipe, parabromoacetophenone and ammonia, the mol ratio of copper powder is 1: 10: 0.05, sealed tube is placed in to 100 ℃ of oil baths, stirring reaction 12 hours, cooling reaction system, open piston, reacted mixed solution is extracted with ethyl acetate, the organic phase anhydrous sodium sulfate drying, 40～50 ℃ of rotary evaporation to dripless are dripped, separate (sherwood oil: ethyl acetate=5: 1) by column chromatography, be prepared into para-aminoacetophenone, its yield is 99.0%.
Products therefrom is characterized with Bruker Avance type superconduction fourier numeralization nuclear magnetic resonance spectrometer, and characterization data is as follows:
1H?NMR(300MHz，d
6-DMSO)δ(ppm)：2.38(s，3H)，6.02(s，2H)，6.55-6.58(d，J＝8.4Hz，2H)，7.65-7.68(d，J＝8.1Hz，2H)。
13C?NMR(75MHz，d
6-DMSO)δ(ppm)：26.3，113.0，125.4，131.0，154.0，195.4。
Nuclear magnetic data shows that products therefrom is para-aminoacetophenone.
The parabromoacetophenone of the present embodiment can be replaced with equimolar parachloroacetophenone, also available equimolar the iodobenzene ethyl ketone is replaced.
Embodiment 8
Take and prepare para-amino benzoic acid as example, the structural formula of para-amino benzoic acid is:
Raw materials used and preparation method thereof be: in the 25mL sealed tube, add the 0.032g copper powder, 2.012g parabromobenzoic acid, 7.0mL the ammonia soln that massfraction is 30%, piston on the screwing hermetic pipe, parabromobenzoic acid and ammonia, the mol ratio of copper powder is 1: 10: 0.05, sealed tube is placed in to 100 ℃ of oil baths, stirring reaction 12 hours, cooling reaction system, open piston, the salt acid for adjusting pH value to 2 that reacted mixed solution is 37% with massfraction～3, be extracted with ethyl acetate, the organic phase anhydrous sodium sulfate drying, 40～50 ℃ of rotary evaporation to dripless are dripped, separate (sherwood oil: ethyl acetate=1: 1) by column chromatography, be prepared into para-amino benzoic acid, its yield is 95.4%.
Products therefrom is characterized with Bruker Avance type superconduction fourier numeralization nuclear magnetic resonance spectrometer, and characterization data is as follows:
1H?NMR(300MHz，d
6-DMSO)δ(ppm)：5.86(s，2H)，6.53-6.56(d，J＝8.7Hz，2H)，7.60-7.63(d，J＝8.4Hz，2H)，11.96(s，1H)。
13C?NMR(75MHz，d
6-DMSO)δ(ppm)：113.1，117.4，131.7，153.6，168.0。
Nuclear magnetic data shows that products therefrom is para-amino benzoic acid.
The parabromobenzoic acid of the present embodiment can be replaced with equimolar Chlorodracylic acid, and also available equimolar 4-Iodobenzoic acid is replaced.
Embodiment 9
Take and prepare p-Chlorobenzoic acid amide as example, the structural formula of p-Chlorobenzoic acid amide is:
Raw materials used and preparation method thereof be: in the 25mL sealed tube, add the 0.032g copper powder, 1.914g para chlorobromobenzene, 7.0mL the ammonia soln that massfraction is 30%, piston on the screwing hermetic pipe, para chlorobromobenzene and ammonia, the mol ratio of copper powder is 1: 10: 0.05, sealed tube is placed in to 100 ℃ of oil baths, stirring reaction 12 hours, cooling reaction system, open piston, reacted mixed solution is extracted with ethyl acetate, the organic phase anhydrous sodium sulfate drying, 40～50 ℃ of rotary evaporation to dripless are dripped, separate (sherwood oil: ethyl acetate=5: 1) by column chromatography, be prepared into p-Chlorobenzoic acid amide, its yield is 98.1%.
Products therefrom is characterized with Bruker Avance type superconduction fourier numeralization nuclear magnetic resonance spectrometer, and characterization data is as follows:
1H?NMR(300MHz，d
6-DMSO)δ(ppm)：5.20(s，2H)，6.54-6.57(d，J＝8.7Hz，2H)，7.00-7.03(d，J＝8.4Hz，2H)。
13C?NMR(75MHz，d
6-DMSO)δ(ppm)：115.7，119.4，128.9，148.1。
Nuclear magnetic data shows that products therefrom is p-Chlorobenzoic acid amide.
Embodiment 10
The preparation of take is example to cyano-aniline, to the structural formula of cyano-aniline, is:
Raw materials used and preparation method thereof be: in the 25mL sealed tube, add the 0.032g copper powder, 1.820g to the cyano group bromobenzene, 7.0mL the ammonia soln that massfraction is 30%, piston on the screwing hermetic pipe, to cyano group bromobenzene and ammonia, the mol ratio of copper powder is 1: 10: 0.05, sealed tube is placed in to 100 ℃ of oil baths, stirring reaction 12 hours, cooling reaction system, open piston, reacted mixed solution is extracted with ethyl acetate, the organic phase anhydrous sodium sulfate drying, 40～50 ℃ of rotary evaporation to dripless are dripped, separate (sherwood oil: ethyl acetate=5: 1) by column chromatography, be prepared into cyano-aniline, its yield is 80.2%.
Products therefrom is characterized with Bruker Avance type superconduction fourier numeralization nuclear magnetic resonance spectrometer, and characterization data is as follows:
1H?NMR(300MHz，d
6-DMSO)δ(ppm)：5.58(s，2H)，6.50-6.53(d，J＝7.8Hz，2H)，6.56-6.59(d，J＝7.8Hz，2H)。
13C?NMR(75MHz，d
6-DMSO)δ(ppm)：113.0，121.5，129.6，152.1，168.5。
Nuclear magnetic data shows that products therefrom is to cyano-aniline.
Embodiment 11
With preparation 2-amino-4, the 5-dimethoxy benzaldehyde is example, and its structural formula is:
Raw materials used and preparation method thereof be: in the 25mL sealed tube, add the 0.032g copper powder, 2.451g 2-bromo-4, the 5-dimethoxy benzaldehyde, 7.0mL the ammonia soln that massfraction is 30%, piston on the screwing hermetic pipe, 2-bromo-4, 5-dimethoxy benzaldehyde and ammonia, the mol ratio of copper powder is 1: 10: 0.03, sealed tube is placed in to 100 ℃ of oil baths, stirring reaction 18 hours, cooling reaction system, open piston, reacted mixed solution is extracted with ethyl acetate, the organic phase anhydrous sodium sulfate drying, 40～50 ℃ of rotary evaporation to dripless are dripped, separate (sherwood oil: ethyl acetate=5: 1) by column chromatography, be prepared into 2-amino-4, the 5-dimethoxy benzaldehyde, its yield is 82.4%.
Products therefrom is characterized with Bruker Avance type superconduction fourier numeralization nuclear magnetic resonance spectrometer, and characterization data is as follows:
1H?NMR(300MHz，d
6-DMSO)δ(ppm)：3.69(s，3H)，3.78(s，3H)，6.33(s，1H)，6.99(s，3H)，9.63(s，1H)。
13C?NMR(75MHz，d
6-DMSO)δ(ppm)：55.9，56.5，98.6，110.8，116.6，140.3，148.6，156.4，191.4。
Nuclear magnetic data shows that products therefrom is 2-amino-4, the 5-dimethoxy benzaldehyde.
Embodiment 12
The preparation 2-amino naphthalenes of take is example, and the structural formula of 2-amino naphthalenes is:
Raw materials used and preparation method thereof be: in the 25mL sealed tube, add the 0.032g copper powder, 2.071g β-bromonaphthalene, 7.0mL the ammonia soln that massfraction is 30%, piston on the screwing hermetic pipe, β-bromonaphthalene and ammonia, the mol ratio of copper powder is 1: 10: 0.05, sealed tube is placed in to 100 ℃ of oil baths, stirring reaction 12 hours, cooling reaction system, open piston, reacted mixed solution is extracted with ethyl acetate, the organic phase anhydrous sodium sulfate drying, 40～50 ℃ of rotary evaporation to dripless are dripped, separate (sherwood oil: ethyl acetate=5: 1) by column chromatography, be prepared into the 2-amino naphthalenes, its yield is 92.8%.
Products therefrom is characterized with Bruker Avance type superconduction fourier numeralization nuclear magnetic resonance spectrometer, and characterization data is as follows:
1H?NMR(300MHz，d
6-DMSO)δ(ppm)：5.35(s，2H)，6.81(s，1H)，6.92-6.94(d，J＝7.2Hz，1H)，7.05-7.10(t，1H)，7.24-7.29(t，1H)，7.47-7.50(d，J＝8.4Hz，1H)，7.56-7.63(t，2H)。
13C?NMR(75MHz，d
6-DMSO)δ(ppm)：106.4，118.9，121.3，125.5，126.3，127.9，128.9，135.5，147.1。
Nuclear magnetic data shows that products therefrom is the 2-amino naphthalenes.
Embodiment 13
The preparation 3-aminopyridine of take is example, and the structural formula of 3-aminopyridine is:
Raw materials used and preparation method thereof be: add the 0.032g copper powder in the 25mL sealed tube, 1.580g 3-bromopyridine, 7.0mL the ammonia soln that massfraction is 30%, piston on the screwing hermetic pipe, 3-bromopyridine and ammonia, the mol ratio of copper powder is 1: 10: 0.05, sealed tube is placed in to 100 ℃ of oil baths, stirring reaction 10 hours, cooling reaction system, open piston, reacted mixed solution is extracted with ethyl acetate, the organic phase anhydrous sodium sulfate drying, 40～50 ℃ of rotary evaporation to dripless are dripped, separate (sherwood oil: ethyl acetate=5: 1) by column chromatography, be prepared into the 3-aminopyridine, its yield is 93.5%.
Products therefrom is characterized with Bruker Avance type superconduction fourier numeralization nuclear magnetic resonance spectrometer, and characterization data is as follows:
1H?NMR(300MHz，d
6-DMSO)δ(ppm)：5.26(s，2H)，6.88-6.90(d，J＝6.9Hz，1H)，6.99-7.01(t，1H)，7.23(s，1H)，7.93(s，1H)。
13C?NMR(75MHz，d
6-DMSO)δ(ppm)：120.2，124.1，136.9，137.5，145.3。
Nuclear magnetic data shows that products therefrom is the 3-aminopyridine.
Embodiment 14
The preparation 3-aminothiophene of take is example, and the structural formula of 3-aminothiophene is:
Raw materials used and preparation method thereof be: in the 25mL sealed tube, add the 0.032g copper powder, 1.630g 3 bromo thiophene, 7.0mL the ammonia soln that massfraction is 30%, piston on the screwing hermetic pipe, 3 bromo thiophene and ammonia, the mol ratio of copper powder is 1: 10: 0.05, sealed tube is placed in to 100 ℃ of oil baths, stirring reaction 16 hours, cooling reaction system, open piston, reacted mixed solution is extracted with ethyl acetate, the organic phase anhydrous sodium sulfate drying, 40～50 ℃ of rotary evaporation to dripless are dripped, separate (sherwood oil: ethyl acetate=5: 1) by column chromatography, be prepared into the 3-aminothiophene, its yield is 58.6%.
Products therefrom is characterized with Bruker Avanc e type superconduction fourier numeralization nuclear magnetic resonance spectrometer, and characterization data is as follows:
1H?NMR(300MHz，d
6-DMSO)δ(ppm)：4.75(s，2H)，5.98(s，2H)，6.58-6.60(d，J＝4.2Hz，1H)，7.15-7.16(d，J＝2.7Hz，1H)。
13C?NMR(75MHz，d
6-DMSO)δ(ppm)：96.7，121.8，124.9，147.9。
Nuclear magnetic data shows that products therefrom is the 3-aminothiophene.
Embodiment 15
The preparation N-phenylethylenediamine of take is example, and the structural formula of N-phenylethylenediamine is
Raw materials used and preparation method thereof be: in the 25mL sealed tube, add the 0.032g copper powder, 1.560g bromobenzene, 3.005g quadrol, 1mL distilled water, piston on the screwing hermetic pipe, bromobenzene and quadrol, the mol ratio of copper powder is 1: 5: 0.05, sealed tube is placed in to 120 ℃ of oil baths, stirring reaction 0.3 hour, cooling reaction system, open piston, reacted mixed solution is extracted with ethyl acetate, the organic phase anhydrous sodium sulfate drying, 40～50 ℃ of rotary evaporation to dripless are dripped, separate (sherwood oil: ethyl acetate=3: 1 by column chromatography, sherwood oil: ethyl acetate=1: 1, ethyl acetate, gradient elution), be prepared into the N-phenylethylenediamine, its yield is 99.3%.
Products therefrom is characterized with Bruker Avance type superconduction fourier numeralization nuclear magnetic resonance spectrometer, and characterization data is as follows:
1H?NMR(300MHz，d
6-DMSO)δ(ppm)：2.06(s，2H)，2.70-2.73(t，J＝5.0Hz，2H)，2.99(s，2H)，5.56(s，1H)，6.50-6.58(q，3H)，7.04-7.09(t，J＝6.6Hz，2H)。
13C?NMR(75MHz，d
6-DMSO)δ(ppm)：40.7，46.1，112.0，115.5，128.8，149.0。
Nuclear magnetic data shows that products therefrom is the N-phenylethylenediamine.
Embodiment 16
The preparation N-phenyl propylene diamine of take is example, and the structural formula of N-phenyl propylene diamine is
Raw materials used and preparation method thereof be: in the 25mL sealed tube, add the 0.032g copper powder, 1.560g bromobenzene, 3.706g propylene diamine, 2mL distilled water, piston on the screwing hermetic pipe, bromobenzene and propylene diamine, the mol ratio of copper powder is 1: 5: 0.05, sealed tube is placed in to 100 ℃ of oil baths, stirring reaction 0.5 hour, cooling reaction system, open piston, reacted mixed solution is extracted with ethyl acetate, the organic phase anhydrous sodium sulfate drying, 40～50 ℃ of rotary evaporation to dripless are dripped, separate (sherwood oil: ethyl acetate=3: 1 by column chromatography, sherwood oil: ethyl acetate=1: 1, ethyl acetate, gradient elution), be prepared into N-phenyl propylene diamine, its yield is 95.5%.
Products therefrom is characterized with Bruker Avance type superconduction fourier numeralization nuclear magnetic resonance spectrometer, and characterization data is as follows:
1H?NMR(300MHz，d
6-DMSO)δ(ppm)：1.56-1.65(m，2H)，1.81(s，1H)，2.61-2.65(t，J＝6.6Hz，3H)，3.02(s，2H)，5.51(s，1H)，6.47-6.56(q，3H)，7.02-7.07(q，2H)。
13C?NMR(75MHz，d
6-DMSO)δ(ppm)：13.8，19.9，30.9，42.5，111.8，115.2，128.7，149.1。
Nuclear magnetic data shows that products therefrom is N-phenyl propylene diamine.
Embodiment 17
The preparation N-phenylethyl alcohol of take is example, and the structural formula of N-phenylethyl alcohol is
Raw materials used and preparation method thereof be: in the 25mL sealed tube, add the 0.032g copper powder, 1.560g bromobenzene, 3.054g monoethanolamine, piston on the screwing hermetic pipe, bromobenzene and monoethanolamine, the mol ratio of copper powder is 1: 5: 0.05, sealed tube is placed in to 100 ℃ of oil baths, stirring reaction 12 hours, cooling reaction system, open piston, reacted mixed solution is extracted with ethyl acetate, the organic phase anhydrous sodium sulfate drying, 40～50 ℃ of rotary evaporation to dripless are dripped, separate (sherwood oil: ethyl acetate=3: 1 by column chromatography, sherwood oil: ethyl acetate=1: 1, ethyl acetate, gradient elution), be prepared into the N-phenylethyl alcohol, its yield is 86.3%.
Products therefrom is characterized with Bruker Avance type superconduction fourier numeralization nuclear magnetic resonance spectrometer, and characterization data is as follows:
1H?NMR(300MHz，d
6-DMSO)δ(ppm)：3.07-3.09(d，J＝5.4Hz，2H)，3.54-3.56(d，J＝5.7Hz，2H)，4.68(s，1H)，5.43(s，1H)，6.56-6.58(d，J＝7.8Hz，3H)，7.06-7.08(d，J＝7.2Hz，2H)。
13C?NMR(75MHz，d
6-DMSO)δ(ppm)：45.1，59.2，111.6，115.1，128.4，148.4。
Nuclear magnetic data shows that products therefrom is the N-phenylethyl alcohol.
Embodiment 18
The preparation N-phenyl-L-Phe of take is example, and the structural formula of N-phenyl-L-Phe is:
Raw materials used and preparation method thereof be: in the 25mL sealed tube, add the 0.032g copper powder, 1.560g the mixture of bromobenzene and 1.6508g L-Phe and 4mL distilled water, piston on the screwing hermetic pipe, bromobenzene and L-Phe, the mol ratio of copper powder is 1: 1: 0.05, sealed tube is placed in to 100 ℃ of oil baths, stirring reaction 24 hours, cooling reaction system, open piston, the salt acid for adjusting pH value to 2 that reacted mixed solution is 37% with massfraction～3, be extracted with ethyl acetate, the organic phase anhydrous sodium sulfate drying, 40～50 ℃ of rotary evaporation to dripless are dripped, separate (sherwood oil: ethyl acetate=5: 1) by column chromatography, be prepared into N-phenyl-L-Phe, its yield is 78.5%.
Products therefrom is characterized with Bruker Avance type superconduction fourier numeralization nuclear magnetic resonance spectrometer, and characterization data is as follows:
1H?NMR(300MHz，d
6-DMSO)δ(ppm)：2.97-3.08(m，2H)，3.64-3.66(d，J＝0.016Hz，1H)，4.11-4.13(d，J＝0.02Hz，1H)，6.56-6.58(d，J＝0.02Hz，3H)，7.03-7.07(t，2H)，7.20-7.29(q，5H)。
13C?NMR(75MHz，d
6-DMSO)δ(ppm)：46.8，57.9，113.0，116.8，126.8，128.6，129.3，129.6，138.4，148.2，175.1。
Nuclear magnetic data shows that products therefrom is N-phenyl-L-Phe.
Embodiment 19
The preparation N-Santosol 360 of take is example, and its structural formula is:
Raw materials used and preparation method thereof be: in the 25mL sealed tube, add 0.032g copper powder, 1.560g bromobenzene, 4.959g benzylamine, piston on the screwing hermetic pipe, the mol ratio of bromobenzene and benzylamine, copper powder is 1: 5: 0.05, sealed tube is placed in to 100 ℃ of oil baths, stirring reaction 24 hours, cooling reaction system, open piston, reacted mixed solution is extracted with ethyl acetate, the organic phase anhydrous sodium sulfate drying, 40～50 ℃ of rotary evaporation to dripless are dripped, and by column chromatography, separate, be prepared into the N-Santosol 360, its yield is 51.5%.
Products therefrom is characterized with Bruker Avance type superconduction fourier numeralization nuclear magnetic resonance spectrometer, and characterization data is as follows:
1H?NMR(300MHz，d
6-DMSO)δ(ppm)：1.11-1.38(m，6H)，1.62-1.77(m，2H)，2.03-2.06(d，J＝10.2Hz，2H)，3.24(s，1H)6.56-6.67(m，3H)。
13C?NMR(75MHz，d
6-DMSO)δ(ppm)：24.6，25.6，32.6，50.5，112.2，115.0，128.8，147.9。
Nuclear magnetic data shows that products therefrom is the N-Santosol 360.
Embodiment 20
Preparation N-(2-methoxy ethyl) aniline of take is example, and its structural formula is:
Raw materials used and preparation method thereof be: in the 50mL sealed tube, add the 0.032g copper powder, 1.560g bromobenzene, 6.913g 2-methoxyethyl amine, 17.5mL distilled water, piston on the screwing hermetic pipe, bromobenzene and 2-methoxyl group monobromethane, the mol ratio of copper powder is 1: 20: 0.1, the mass ratio of 2-methoxyethyl amine and distilled water is 1: 2.5, sealed tube is placed in to 80 ℃ of oil baths, stirring reaction 24 hours, cooling reaction system, open piston, reacted mixed solution is extracted with ethyl acetate, the organic phase anhydrous sodium sulfate drying, 40～50 ℃ of rotary evaporation to dripless are dripped, by column chromatography, separate, be prepared into N-(2-methoxy ethyl) aniline.
Embodiment 21
In embodiment 1,4～14, the ammonia soln that the ammonia soln that massfraction used is 30% is 10% with massfraction is replaced, and the ammonia soln that also the available quality mark is 70% is replaced, and the mole number of ammonia is identical with corresponding embodiment.
Claims (1)
1. the organic solvent-free synthetic method of an aromatic amine compound, it is characterized in that: in the 25mL sealed tube, add the 0.032g copper powder, 1.560g bromobenzene, 3.054g monoethanolamine, piston on the screwing hermetic pipe, bromobenzene and monoethanolamine, the mol ratio of copper powder is 1: 5: 0.05, sealed tube is placed in to 100 ℃ of oil baths, stirring reaction 12 hours, cooling reaction system, open piston, reacted mixed solution is extracted with ethyl acetate, the organic phase anhydrous sodium sulfate drying, 40～50 ℃ of rotary evaporation to dripless are dripped, by column chromatography, separate, sherwood oil: ethyl acetate=3: 1, sherwood oil: ethyl acetate=1: 1, ethyl acetate, gradient elution, be prepared into the N-phenylethyl alcohol, its yield is 86.3%.
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| CN104478737B (en) * | 2014-11-22 | 2017-01-18 | 陈定奔 | Synthetic method for preparing primary arylamine by utilizing ammonia water as raw material |
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