CN102050687B - Method for preparing aromatic primary amine by taking ammonia water as ammonia source in water phase system - Google Patents
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Abstract
The invention provides a method for preparing aromatic primary amine by taking ammonia water as an ammonia source in a water phase system. In the method, aromatic halogenate and the ammonia water are used as raw materials, water is used as a solvent, at room temperature or under the heating condition of common oil bath, carbonates, fluorides, phosphates and hydroxides of alkali metals or alkaline-earth metals are taken as alkalis, and a catalytic reaction is preformed through adding a surfactant and using a temary catalysis system composed of copper catalyst, hydrazide and ketone. The method has the characteristics that the operation is simple, wide substrate application range is wide, the product is simple and easy to separate, the yield is high, the process is economic and is environment-friendly and the like; and reaction conditions are flexible, thus corresponding room temperature or heating mode can be selected according to practical requirements. In addition, the environment friendliness of the reaction is effectively improved by using water as a reaction solvent, thereby better conforming to the development requirements of green chemistry. Especially, the substrate is wide in application range and has wide application prospects in the aspects of preparing natural products, medicines and pesticides.
Description
Technical field
The present invention relates to technical field of chemistry, relate in particular to the aromatic halogenate of copper catalysis in aqueous phase system and the method that aromatic primary amine is prepared in ammoniacal liquor reaction.
Technical background
Aromatic primary amine is that a kind of important organic synthesis becomes intermediate, also be the important intermediate in agrochemicals, dyestuff, medicine and some other chemical materials manufacturing processed, be widely used in ((a) K.Weissermel in agricultural chemicals, medicine and Materials science, H.J.Arpe, Industry Organic Chemistry, Wiley-VCH, Weinheim, 1997; (b) S.A.Lawrence, Amines:Synthesis Properties, and Application, Cambridge University Press, Cambridge, 2004.).Therefore, how more convenient, prepare aromatic primary amine compounds efficiently and caused that people pay attention to widely.At present, the method for industrial main employing nitro-aromatic shortening is prepared aromatic primary amine (US 3136818, EP 0696573) both at home and abroad.Also there is patent to disclose a kind of prepared aniline by benzene and ammonia under reducible metal oxide effect method (US 3919155, US 4031106).Because these methods generally need the vigorous reaction condition of high temperature, high pressure, so have the problems such as equipment requirements is high, operation inconvenience, and high-temperature and high-pressure conditions has limited the tolerance of part functional group.Chinese patent CN 1555921A discloses transition metal-catalyzed, take ammoniacal liquor as aminating agent, and the hydrogen peroxide of take is prepared the method for aniline as oxygenant under normal pressure and lesser temps by benzene, but the transformation efficiency of benzene is not ideal enough.Chinese patent CN 1807397 discloses take solubility vanadic salts as catalyzer, compared with under mild conditions, makes the method for the one-step synthesis aniline in acetic aid medium with benzene and oxammonium hydrochloride, and reaction process easy handling, cost are low, but the yield of aniline is still lower.
Ammoniacal liquor be a kind of nitrogenous source cheap and easy to get (D.M.Roundhill, Chem.Rev.1992,92,1.).Utilize aromatic halogenate and ammoniacal liquor reaction directly to synthesize and obtain aromatic primary amine compounds.In recent years, existing lot of documents or patent report achievement in research ((a) Ley, the S.V. of aromatic carbon-nitrogen coupling reaction of palladium or copper catalysis, Thomas, A.W.Angew.Chem.Int.Ed.2003,42,5400, (b) D.S.Surry, S.L.Buchwald, Angew.Chem.Int.Ed.2008,47,6338, (c) J.P.Corbet, Chem.Rev., 2006,106,2651, (d) J.F.Hartwig, Synlett, 2006, 1283.), but in the C-N coupling reaction process at aromatic halogenate and ammoniacal liquor, the aromatic primary amine that reaction generates can form competition with ammoniacal liquor, may cause the even generation of tertiary amine class by product of a large amount of secondary amines, thereby reduce the productive rate of aromatic primary amine, therefore, for prepare the research of the method for aromatic primary amine by aromatic halogenate and reacting of ammoniacal liquor, also exist huge challenge ((a) F.Lang, D.Zewge, I.N.Houpis, R.P.Volante, Tetrahedron Letter.2001, 42, 3251, (b) M.C.Willis, Angew.Chem.Int.Fd.2007,46,3402.).In recent years, by adding suitable ligand compound, adopt the linked reaction of transition metal-catalyzed halogenated aryl hydrocarbon and ammoniacal liquor to make some progress.
At present, increasing bibliographical information method ((a) X.F.Wu, C.Darcel, Eur.J.Org.Chem.2009,4753 of preparing aromatic primary amine by aromatic halogenate of copper catalysis; (b) N.Xia, M.Taillefer, Angew.Chem.Int.Ed.2009,48,337; (c) H.Wu, C.Wolf, Chem.Commun.2009,3035; (d) D.Wang, Q.Cai, K.Ding, Adv.Synth.Catal.2009,351,1722; (e) C.T.Yang, Y.Fu, Y.B.Huang, J.Yi, Q.X.Guo, L.Liu, Angew.Chem.2009,121,7534, Angew.Chem.Int.Ed.2009,48,7398; (f) L.Jiang, X, Lu, H.Zhang, Y.Jiang, D.Ma, J.Org.Chem.2009,74,4546).But these reactions are normally carried out in organic solvent, and the most complex structures of the part adopting, price is higher, is difficult to obtain.Along with the raising day by day of mankind's environmental consciousness, and the proposition of Green Chemistry concept, how to reduce so that eliminate the objectionable impurities of discharging in chemical industry become mankind's growing interest and problem demanding prompt solution.
Compare the feature such as that glassware for drinking water has is inexpensive, safety, environmental friendliness with organic solvent.So the water of usining is applied in organic synthesis as reaction medium, is to be hopeful to realize one of industrialized green synthesis method most.Water organic synthesis has become the key areas of current Green Chemistry research, in aqueous phase system, the organic reaction of metal or organocatalysis has also obtained certain progress ((a) D.Dallinger, C.O.Kappe, Chem.Rev.2007,107,2563; (b) M.Carril, R.SanMartin, E.Dom í nguez, Chem.Soc.Rev.2008,37,639; (c) X.Zhu, L.Su, Y.wan, et al., Eur.J.Org.Chem.2009,635; (d) J.Xie, X.Zhu, Y.Wan, et al., Eur.J.Org.Chem.2010,3219.).In aqueous phase system, the report of the aromatic halogenate of copper catalysis and the linked reaction of ammoniacal liquor is also relative less, the people such as Zhou have reported halogenated aryl hydrocarbon in a kind of water of copper complex catalysis and the coupling method (Z.Wu of ammoniacal liquor, Z.Jiang, X.Zhou, et at., Eur.J.Org.Chem.2010,1854.), but temperature of reaction is relatively high, the time is longer.The people such as Wan have reported with N
2, N
2the halogenated aryl hydrocarbon of copper catalysis that '-di-isopropyl oxalyl hydrazine is part and the coupling method of ammoniacal liquor (F.Meng, X.Zhu, Y.Wan, et al., Eur.J.Org.Chem.2010,6149.), but longer at lesser temps the reaction time, and exist certain substrate limitation.
The present invention is under state natural sciences fund (20802095,20872182) is subsidized, and is the research that provides the preparation method of a kind of economy, gentleness, eco-friendly aromatic primary amine to carry out.
Summary of the invention
The object of the present invention is to provide a kind of easy, reaction conditions is gentle, the synthetic method of the aromatic primary amine of wide application range of substrates, environmental friendliness, process economy.
The present invention take ammoniacal liquor as ammonia source, to prepare the method for aromatic primary amine in a kind of aqueous phase system, take aromatic halogenate and ammoniacal liquor as raw material, using water as solvent, under room temperature or common heating condition, carbonate, fluorochemical, phosphoric acid salt and the oxyhydroxide of basic metal or alkaline-earth metal of take is alkali, and add tensio-active agent, it is characterized in that the three-element catalytic system catalysis aromatic halogenate or nitrogen-containing hetero lopps halides and the ammoniacal liquor reaction formation primary amine that with various copper catalysts, oxalyl hydrazine and ketone, form.
In the present invention, involved reaction can adopt following reaction formula to represent:
In formula, X-is selected from iodine or bromine;
Ar is selected from 2-or 3-or 4-bit strip substituent aromatic nucleus, or with the aromatic nucleus of two replacements or multi-substituent; Aromatic nucleus comprises phenyl ring, naphthalene nucleus and pyridine ring, and X-the position of substitution of pyridine ring can be in 2-or 3-position; Substituting group can be hydrogen, nitro, ethanoyl, alkyl, alkoxyl group, aryl, halogen, trifluoromethyl etc. but not only be confined to these substituting groups;
Concrete reaction process of the present invention is: copper catalyst, oxalyl hydrazine, ketone, aryl halides, alkali, tensio-active agent, ammoniacal liquor and water are added to reaction tubes successively, seal, adopt the mode stirring reaction of common heating bath heating or direct room temperature reaction; After reaction finishes, separating reaction mixed solution purifying, obtain aromatic primary amine product.
Below the inventive method is further described:
(1) reaction solvent is water cheap and easy to get, and environmental friendliness;
(2) reaction can at room temperature be carried out, and the reaction times is 6-96h, is preferably 12-72h; Reaction can also adopt the method for common heating bath heating, and temperature of reaction is 50-140 ℃, is preferably 60-120 ℃, and the reaction times is 5-180min, is preferably 5-120min;
(3) reactant aromatic halogenate can be substituted or non-substituted, and the mol ratio of aromatic halogenate and ammoniacal liquor is preferably 1: 2 to 1: 8;
(4) copper catalyst using can be the oxide compound of metallic copper, copper and the mantoquita of various monovalence or divalence, as: copper sulfate, cupric nitrate, cupric chloride, neutralized verdigris, cuprous chloride, cuprous iodide etc., the mol ratio of catalyzer and substrate aryl halides is preferably 1: 40 to 1: 2;
(5) part using is two parts of oxalyl hydrazine and ketone, ketone can be chain single ketones, ring-type single ketones, chain diketone, cyclic diketones, aromatic ketone, as: acetone, butanone, methyl isopropyl ketone, methyl-n-butyl ketone, 2,5-hexanedione, 2,3-dimethyl diketone, cyclopentanone, pimelinketone etc., the mol ratio of part oxalyl hydrazine and the ketone of using is preferably 1: 1 to 1: 6; The mol ratio of hydrazides and catalyzer is preferably 2: 1 to 20: 1;
(6) alkali used can be carbonate, phosphoric acid salt, fluorochemical, borate and the oxyhydroxide of basic metal or alkaline-earth metal or the compound that can be converted into respective compound in water; The mol ratio of alkali and substrate aromatic halogenate is preferably 1.5: 1 to 3: 1;
(7) tensio-active agent using can be quaternary ammonium salt, season phosphonium salt class, dodecane sulfonate class, PEG class etc., but be not only confined to these tensio-active agents; The mol ratio of tensio-active agent and substrate aryl halides is preferably 1: 20 to 1: 2.
The inventive method is simple to operate, wide application range of substrates, product are simply easy to separation and purification, productive rate is high, process economy and environmental friendliness.Because reaction conditions is more flexible, so can be according to the actual needs, carry out corresponding selective reaction condition, can adopt under room temperature condition reaction (save energy, be adapted to heat-labile substrate, but the time of reaction being relatively long) or adopt the method (can significantly shorten the time of reaction) of heating bath heating.Secondly, the catalyzer adopting in the method and part are business and can obtain, without synthetic, and inexpensive, stablize, be easy to obtain.In addition, this reaction is usingd water as solvent, with the reacting phase ratio of the same type of reporting in document, effectively improved the environment friendly of reaction, requirement, especially its wide application range of substrates of more meeting Green Chemistry development, have broad prospects aspect preparing at natural product, medicine and agricultural chemicals.
Embodiment
Below in conjunction with embodiment, content of the present invention is described further.
Embodiment 1: P-nethoxyaniline synthetic
By 4mg (0.025mmol) CuO, 24mg (0.2mmol) oxalyl hydrazine, 57mg (0.5mmol) 2,5-hexanedione, 187mg (1.0mmol) is to methoxyl group bromobenzene, 840mg (6.0mmol) ammoniacal liquor, 112mg (2.0mmol) KOH, 81mg (0.25mmol) TBAB, 1ml water adds in 10ml reaction tubes, under room temperature condition, stirs 72h.After reaction stops, be extracted with ethyl acetate, water and saturated common salt washing respectively again, after anhydrous sodium sulfate drying, filter, solvent is removed in underpressure distillation, and the reaction mixture obtaining is through silicagel column column chromatography for separation purification [eluent: petrol ether/ethyl acetate (20: 1)], obtain P-nethoxyaniline 107mg, yield 87%.
ESI-MS：m/z＝124[M+H]
+；
1H?NMR(300MHz，CDCl
3)：δ6.72(d，J＝8.8Hz，2H)，6.62(d，J＝8.8Hz，2H)，3.72(s，3H)，3.24(br?s，2H)。
Embodiment 2: p-Nitroaniline synthetic
By 63mg (0.25mmol) CuSO
45H
2o, 59mg (0.5mmol) oxalyl hydrazine, 200mg (2.0mmol) methyl-n-butyl ketone, 202mg (1.0mmol) is to nitro bromobenzene, 560mg (4.0mmol) ammoniacal liquor, 168mg (3.0mmol) KOH, 32.2mg (0.1mmol) TBAB, 1ml H
2o adds in 10ml reaction tubes, stirring reaction 30min at 90 ℃ of common oil bath heating.After reaction stops, be extracted with ethyl acetate, water and saturated common salt washing respectively again, after anhydrous sodium sulfate drying, filter, underpressure distillation is except desolventizing, and the reaction mixture obtaining is through silicagel column column chromatography for separation purification [eluent: petrol ether/ethyl acetate (10: 1)], obtain p-Nitroaniline 112mg, yield 81%.
ESI-MS：m/z＝139[M+H]
+；
1H?NMR(300MHz，DMSO)：δ7.90(d，J＝9.2Hz，2H)，6.67(s，2H)，6.56(d，J＝9.2Hz，2H)。
Embodiment 3: p-Chlorobenzoic acid amide synthetic
By 19mg (0.1mmol) CuI, 59mg (0.5mmol) oxalyl hydrazine, 57mg (0.5mmol) 2,5-hexanedione, 192mg (1.0mmol) para chlorobromobenzene, 1.6g (10.0mmol) ammoniacal liquor, 56mg (1.0mmol) KOH, PEG400 (0.2ml), 2.0ml H
2o adds in 10ml reaction tubes, stirring reaction 5min under 120 ℃ of conditions of common oil bath heating.After reaction stops, be extracted with ethyl acetate, washing, saturated common salt washing, after anhydrous sodium sulfate drying, filters, underpressure distillation desolventizing, the reaction mixture obtaining is purified by [eluent: petrol ether/ethyl acetate (20: 1)] through silicagel column column chromatography for separation, obtains p-Chlorobenzoic acid amide 104mg, yield 82%.
ESI-MS：m/z＝128[M+H]
+；
1H?NMR(300MHz，CDCl
3)：δ7.09(d，J＝8.8Hz，2H)，6.60(d，J＝8.8Hz，2H)，3.68(br?s，2H)。
Embodiment 4: to synthesizing of ethanoyl aniline
By 3.2mg (0.05mmol) Cu, 35mg (0.3mmol) oxalyl hydrazine, 100mg (1.0mmol) pimelinketone, 246mg (1.0mmol) is to ethanoyl iodobenzene, 560mg (4.0mmol) ammoniacal liquor, 424mg (2.0mmol) K
3pO
4, 136mg (0.5mmol) SDS-Na, 2ml H
2o adds in 10ml reaction tubes, stirring reaction 60min at 60 ℃ of common oil bath heating.After reaction stops; be extracted with ethyl acetate; water and saturated common salt washing respectively again; after anhydrous sodium sulfate drying; filter, underpressure distillation is except desolventizing, and the reaction mixture obtaining is through silicagel column column chromatography for separation purification [eluent: petrol ether/ethyl acetate (10: 1)]; obtain ethanoyl aniline 81mg, yield 60%.
ESI-MS：m/z＝136[M+H]
+；
1H?NMR(300MHz，CDCl
3)：δ7.76(d，J＝8.7Hz，2H)，6.61(d，J＝8.8Hz，2H)，4.09(br?s，2H)，2.47(s，3H)。
Embodiment 5: p-trifluoromethylaniline synthetic
By 2mg (0.025mmol) CuO, 30mg (0.25mmol) oxalyl hydrazine, 87mg (1.5mmol) acetone, 113mg (0.5mmol) is to methyl bromobenzene trifluoride, 700mg (5.0mmol) ammoniacal liquor, 272mg (1.0mmol) Cs
2cO
3, 8.05mg (0.025mmol) TBAB, 1.5ml H
2o adds in 10ml reaction tubes, under 100 ℃ of conditions of common oil bath heating, reacts 20min.After reaction stops, be extracted with ethyl acetate, washing, saturated common salt washing, after anhydrous sodium sulfate drying, filters, underpressure distillation desolventizing, the reaction mixture obtaining is purified by [eluent: petrol ether/ethyl acetate (20: 1)] through silicagel column column chromatography for separation, obtains p-trifluoromethylaniline 103mg, yield 64%.
ESI-MS：m/z＝162[M+H]
+；
1H?NMR(300MHz，CDCl
3)：δ7.35(d，J＝8.2Hz，2H)，6.64(d，J＝8.3Hz，2H)，3.90(br?s，2H)。
Embodiment 6: m-anisidine synthetic
By 14mg (0.1mmol) Cu
2o, 30mg (0.25mmol) oxalyl hydrazine, 108mg (1.5mmol) butanone, 187mg (1.0mmol) meta-methoxy bromobenzene, 560mg (4.0mmol) ammoniacal liquor, 207mg (1.5mmol) K
2cO
3, 70mg (0.25mmol) TBAC, 1ml H
2o adds in 10ml reaction tubes, stirring reaction 72h under room temperature.After reaction stops, be extracted with ethyl acetate, washing, saturated common salt washing, after anhydrous sodium sulfate drying, filters, underpressure distillation desolventizing, the reaction mixture obtaining is purified by [eluent: petrol ether/ethyl acetate (20: 1)] through silicagel column column chromatography for separation, obtains m-anisidine 114mg, yield 93%.
ESI-MS：m/z＝124[M+H]
+；
1H?NMR(300MHz，CDCl
3)：δ7.02(t，J＝8.0Hz，1H)，6.26(m，3H)，3.73(s，3H)，3.45(br?s，2H)。
Embodiment 7: m-chloro aniline synthetic
By 4mg (0.05mmol) CuO, 24mg (0.2mmol) oxalyl hydrazine, 58.8mg (0.6mmol) pimelinketone, chloroiodobenzone between 238mg (1.0mmol), 1.12g (8.0mmol) ammoniacal liquor, 112mg (2.0mmol) KOH, 32mg (0.1mmol) TBAB, 1.0ml H
2o adds in 8ml reaction tubes, stirring reaction 24h under room temperature condition.After reaction stops, be extracted with ethyl acetate, washing, saturated common salt washing, after anhydrous sodium sulfate drying, filters, underpressure distillation desolventizing, the reaction mixture obtaining is purified by [eluent: petrol ether/ethyl acetate (20: 1)] through silicagel column column chromatography for separation, obtains m-chloro aniline 108mg, yield 85%.
ESI-MS：m/z＝128[M+H]
+；
1H?NMR(300MHz，CDCl
3)：δ7.01(t，J＝7.9Hz，1H)，6.70-6.62(m，2H)，6.51-6.48(m，1H)，3.68(br?s，2H)。
Embodiment 8: ORTHO ANISIDINE synthetic
By 19mg (0.1mmol) CuI, 24mg (0.2mmol) oxalyl hydrazine, 86.4mg (1.2mmol) butanone, 234mg (1.0mmol) O-methoxy iodobenzene, 1.60g (10.0mmol) ammoniacal liquor (ratio exceeds claims scope), 112mg (2.0mmol) KOH, 140mg (0.5mmol) TBAC, 1.0ml H
2o adds in 10ml reaction tubes, common oil bath heating stirring reaction 120min under 120 ℃ of conditions.After reaction stops, be extracted with ethyl acetate, washing, saturated common salt washing, after anhydrous sodium sulfate drying, filters, underpressure distillation desolventizing, the reaction mixture obtaining is purified by [eluent: petrol ether/ethyl acetate (20: 1)] through silicagel column column chromatography for separation, obtains ORTHO ANISIDINE 103mg, yield 84%.
ESI-MS：m/z＝124[M+H]
+；
1H?NMR(300MHz，CDCl
3)：δ6.78(m，4H)，3.87(s，3H)，3.80(br?s，2H)。
Embodiment 9: aniline synthetic
By 4mg (0.05mmol) CuO, 59mg (0.5mmol) oxalyl hydrazine, 86mg (1.0mmol) methyl isopropyl ketone, 204mg (1.0mmol) iodobenzene, 980mg (7.0mmol) ammoniacal liquor, 138mg (1.0mmol) K
2cO
3, 57mg (0.25mmol) TEBAC, 1.0ml H
2o adds in 10ml reaction tubes, stirring reaction 36h under room temperature.After reaction stops, be extracted with ethyl acetate, washing, saturated common salt washing, after anhydrous sodium sulfate drying, filters, underpressure distillation desolventizing, the reaction mixture obtaining is purified by [eluent: petrol ether/ethyl acetate (20: 1)] through silicagel column column chromatography for separation, obtains aniline 79mg, yield 85%.
ESI-MS：m/z＝94[M+H]
+?
1H?NMR(300MHz，CDCl
3)：δ7.18-7.09(m，2H)，6.74-6.71(m，lH)，6.69-6.62(m，2H)，3.46(br?s，2H)。
Embodiment 10:3,5-xylidine synthetic
By 5mg (0.025mmol) CuI, 36mg (0.3mmol) oxalyl hydrazine, 84mg (1.0mmol) cyclopentanone, 232mg (1.0mmol) 3,5-dimethyl iodobenzene, 840mg (6.0mmol) ammoniacal liquor, 276mg (2.0mmol) K
2cO
3, 255mg (0.5mmol) n-hexadecyl three normal-butyl bromination phosphines, 1.0ml H
2o adds in 10ml reaction tubes, stirring reaction 54h under room temperature.After reaction stops, be extracted with ethyl acetate, washing, saturated common salt washing, after anhydrous sodium sulfate drying, filter, underpressure distillation desolventizing, the reaction mixture obtaining is purified by [eluent: petrol ether/ethyl acetate (20: 1)] through silicagel column column chromatography for separation, obtains 3,5-xylidine 97mg, yield 80%.
ESI-MS：m/z＝122[M+H]
+；
1H?NMR(300MHz，CDCl
3)：δ6.41(s，1H)，6.32(s，2H)，3.37(br?s，2H)，2.22(s，6H)。
Embodiment 11: an amido pyridine synthetic
By 13mg (0.05mmol) CuSO
45H
2o, 59mg (0.5mmol) oxalyl hydrazine, 168mg (2.0mmol) cyclopentanone, bromopyridine between 158mg (1.0mmol), 560mg (4.0mmol) ammoniacal liquor, 276mg (2.0mmol) K
2cO
3, 70mg (0.3mmol) TEBAC, 1.0ml H
2o adds in 10ml reaction tubes, stirring reaction 48h under room temperature.After reaction stops, be extracted with ethyl acetate, washing, saturated common salt washing, after anhydrous sodium sulfate drying, filters, underpressure distillation desolventizing, the reaction mixture obtaining is purified by [eluent: petrol ether/ethyl acetate (5: 1)] through silicagel column column chromatography for separation, obtains an aminopyridine 81mg, yield 86%.
ESI-MS：m/z＝95[M+H]
+；
1H?NMR(300MHz，CDCl
3)：δ8.07-7.96(m，2H)，7.05-6.93(m，2H)，3.49(br?s，2H)。
Synthesizing of embodiment 12:1-naphthylamines
By 24.16mg (0.1mmol) CuNO
33H
2o, 236mg (2mmol) oxalyl hydrazine, 673mg (6.0mmol) Isosorbide-5-Nitrae-cyclohexanedione, 207mg (1.0mmol) 1-bromonaphthalene, 280mg (2.0mmol) ammoniacal liquor, 489mg (1.5mmol) Cs
2cO
3, PEG800 (5ml), 1.0ml H
2o adds in 10ml reaction tubes, and under 60 ℃ of conditions of common oil bath heating, stirring reaction is 100 minutes.After reaction stops, be extracted with ethyl acetate, washing, saturated common salt washing, after anhydrous sodium sulfate drying, filters, underpressure distillation desolventizing, the reaction mixture obtaining is purified by [eluent: petrol ether/ethyl acetate (10: 1)] through silicagel column column chromatography for separation, obtains naphthalidine 100mg, yield 70%.
ESI-MS：m/z＝144[M+H]
+；
1H?NMR(300MHz，DMSO-d
6)：δ8.08(d，1H)，7.74(d，1H)，7.42(m，2H)，7.23(t，1H)，7.09(d，1H)，6.70(d，1H)，5.68(s，2H)。
Synthesizing of embodiment 13:4-p-diaminodiphenyl
By 32mg (0.5mmol) Cu, 118mg (1mmol) oxalyl hydrazine, 241mg (2.0mmol) methyl phenyl ketone, 233mg (1.0mmol) 4-bromo biphenyl, 420mg (3.0mmol) ammoniacal liquor, 637mg (3mmol) K
3pO
4, 14mg (0.05mml) TBAC, 1.0ml H
2o adds in 10ml reaction tubes, stirring reaction 12h under room temperature condition.After reaction stops, be extracted with ethyl acetate, washing, saturated common salt washing, after anhydrous sodium sulfate drying, filters, underpressure distillation desolventizing, the reaction mixture obtaining is purified by [eluent: petrol ether/ethyl acetate (10: 1)] through silicagel column column chromatography for separation, obtains 4-p-diaminodiphenyl 139mg, yield 82%.
ESI-MS：m/z＝170[M+H]
+；
1H?NMR(300MHz，CDCl
3)δ7.62-7.50(m，1H)，7.47-7.35(m，2H)，7.33-7.21(m，1H)，6.76(d，J＝8.6Hz，1H)，3.73(s，1H)。
Claims (4)
1. the ammoniacal liquor of take in aqueous phase system is prepared a method for aromatic primary amine as ammonia source, comprise the following steps:
(1) take aryl halides as substrate, take ammoniacal liquor as ammonia source, catalyzer, part, aryl halides, alkali, tensio-active agent, ammoniacal liquor and water are added in reaction tubes successively, adopt the mode of stirring reaction under common oil bath heating or room temperature condition, described aryl halides is iodo thing or bromo-derivative;
(2) after reaction finishes, separating reaction mixed solution purifying, obtain aromatic primary amine product;
It is characterized in that: the aryl of described aryl halides is selected from phenyl, naphthyl, pyridyl, described catalyzer is copper catalyst, for one of following: the oxide compound of metallic copper, copper, cupprous salt, cupric salt, the mol ratio of catalyzer and substrate aromatic halogenate is preferably 1:40 to 1:2; The mol ratio of the consumption of ammoniacal liquor and substrate aromatic halogenate is preferably 2:1 to 10:1; Described part is two parts of oxalyl hydrazine and ketone, and described ketone is selected from 2,5-hexanedione, methyl-n-butyl ketone, pimelinketone, acetone, butanone, methyl isopropyl ketone, cyclopentanone, and the mol ratio of oxalyl hydrazine used and ketone is preferably 1:1 to 1:6; The mol ratio of oxalyl hydrazine and catalyzer is preferably 2:1 to 20:1.
2. as claimed in claim 1ly take ammoniacal liquor and as ammonia source, prepare the method for aromatic primary amine, it is characterized in that described catalyzer is one of following: copper powder, cupric oxide, Red copper oxide, copper sulfate, cupric nitrate, cupric chloride, cuprous chloride, cuprous iodide, neutralized verdigris.
3. as claimed in claim 1ly take ammoniacal liquor and as ammonia source, prepare the method for aromatic primary amine, the kind that it is characterized in that alkali is one of following: potassium hydroxide, sodium hydroxide, salt of wormwood, sodium carbonate, cesium carbonate, cesium fluoride, potassiumphosphate, the mol ratio of the consumption of alkali and substrate aromatic halogenate is preferably 1.5:1 to 3:1.
4. as claimed in claim 1ly take ammoniacal liquor and as ammonia source, prepare the method for aromatic primary amine, it is characterized in that tensio-active agent is selected from quaternary ammonium salt, season phosphonium salt class, dodecane sulfonate class, PEG class, the mol ratio of the consumption of tensio-active agent and substrate aromatic halogenate is preferably 1:20 to 1:2.
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| CN102557958A (en) * | 2012-01-17 | 2012-07-11 | 中山大学 | Green water-phase synthesis method of primary arylamine |
| US8889938B2 (en) | 2012-03-15 | 2014-11-18 | Micromidas, Inc. | Methods of producing para-xylene |
| CN102796005B (en) * | 2012-08-28 | 2014-07-16 | 杭州新德环保科技有限公司 | Synthetic method of N,N'-diisopropylamino ethylamine |
| US10392317B2 (en) | 2012-09-14 | 2019-08-27 | Micromidas, Inc. | Methods of producing para-xylene and terephthalic acid |
| CN102976951A (en) * | 2012-12-01 | 2013-03-20 | 张家港市大伟助剂有限公司 | Preparation method of 2-methyl-1,2-propane diamine |
| CN102976952A (en) * | 2012-12-01 | 2013-03-20 | 张家港市大伟助剂有限公司 | Preparation method of octyl diethylenetriamine |
| CN103739417B (en) * | 2013-09-29 | 2016-08-17 | 中山大学 | A kind of method synthesizing aromatic primary amine in recirculated water phase system |
| CN105985258B (en) * | 2015-01-29 | 2019-08-02 | 上海彩迩文生化科技有限公司 | A kind of Preparation Method And Their Intermediate of benzamide compounds |
| CN106883132B (en) * | 2017-01-18 | 2019-03-22 | 中山大学 | One kind replaces the copper that hydrazides is ligand to be catalyzed C-N coupling method with N, N- bis- |
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