CN101691318A - N-arylation method taking substituted adipic dihydrazide as ligand in aqueous phase system - Google Patents
N-arylation method taking substituted adipic dihydrazide as ligand in aqueous phase system Download PDFInfo
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Abstract
The invention provides an N-arylation method in an aqueous phase system, which is simple and convenient and environmentally friendly, and has mild reaction condition and economic process. The method comprises the following steps: taking aryl halide and amine as raw materials, and water as solvent, metallic copper, or oxide of copper, or cuprous salt or cupric salt as catalytic agent, and using adipic dihydrazide compound as a ligand to generate C-N coupling reaction; the reaction steps are as follows: adding catalyst, ligand, aryl halide, amine, alkali, surface active agent and water into a microwave reactor or a reaction vessel; reacting by stirring by adopting the mode of microwave assistant heating, or common heating bath heating or direct room temperature reaction; separating and purifying the reaction mixed liquor after the reaction is completed to obtain the N-arylation product. The method of the invention has the characteristics of simple operation, wide substrate application range, simple products which can be separated easily, high yield, economic process and environmental friendliness and the like, and takes water as solvent, has wide application range of the substrate, and has wide application prospects in preparation aspects of natural products, drugs and pesticides.
Description
Technical field
The present invention relates to technical field of chemistry, relate in particular to a kind of N-arylation method.
Technical background
Arylamines is the important compound of a class, extensively is present in to have in the natural of physiologically active and the non-natural product, and the C-N key is formed the extensive attention that the research of reacting is subjected to people always.
The Ullmann reaction of carbon-nitrogen cross-coupling was from existing so far history (Ley, the S.V. for a long time of reported first in 1903; Thomas, A.W.Angew.Chem.Int.Ed.2003,42,5400 reach relevant quoted passage).Because this reaction is normally in high boiling polar solvent, carry out under at the copper powder of high temperature, catalytic amount or equivalent as the condition of catalyzer, thereby there is long reaction time, the subsequent disposal difficulty of reaction, the not high drawback of reaction product complexity and reaction yield.Nineteen eighty-three, people such as Migita have found that the earliest the catalytic C-N key of Pd forms reaction (Kosugi, M.; Kameyama, M.; Migita, T.Chem.Lett.1983,927), 1994, Buchwald and Hartwig developed the catalytic C-N key of Pd simultaneously independently and have formed reaction ((a) Guram, A.S.; Buchwald, S.L.J.Am.Chem.Soc.1994,116,7901; (b) Paul, F.; Patt, J.; Hartwig, J.F.J.Am.Chem.Soc.1994,116,5969).Adopt the catalytic C-N key of Pd to form the more traditional Ullmann reaction of reaction and have condition gentleness relatively, reacting phase is to advantage such as simple, need to use high boiling organic solvent but also exist, toxicity is bigger, the price height, and to the shortcomings such as dependency of unstable and hypertoxic organophosphorus ligand, therefore, in recent years, the catalytic Ullmann of Cu reacts the very big development of having got back.People's such as Buckwald patent PCT/US02/12785 (WO 02/085838) and Ley, S.V. and; Thomas, the summary of A.W. (Ley, S.V.; Thomas, A.W.Angew.Chem.Int.Ed.2003,42,5400) in introduced the formation method of the C-N key under the copper katalysis.By adding suitable part, use the mantoquita of catalytic amount, the Ullmann reaction can be carried out under comparatively gentle condition.Yet, no matter adopt which kind of metal catalyst, the N-arylation reaction of being reported in these documents is normally carried out in organic solvent.And all price is higher for the part majority that is adopted, and is difficult to obtain.Therefore, inventing a kind of economy, environmental friendliness and the wide reaction process of suitable substrates scope is the objective requirement of current such reaction, and good application prospects will be arranged.
People such as Pell ó n have reported the catalytic C-N linked reaction of copper in the aqueous solution ((a) Pell ó n, R.F.; Carrasco, R.; Rod é s, L.Synth.Comm.1993,23 (10), 1447; (b) Pell ó n, R.F.; Est é vez-Braun, A.; Docampo, M.L.; Mart í n, A.; Ravelo, A.G.Synlett 2005, (10), 1606), have the aryl halides of carboxyl and the reaction of amine but only be confined to the ortho position.People such as Twieg reported cuprous iodide catalytic be synthetic method (Lu, the Z. of arylamines in the aqueous solution of part with the 2-dimethylaminoethanol; Twieg, R.J.Tetrahedron Lett.2005,46,2997), but only be confined to aromatic halogenate and amino acid or with certain water miscible short-chain fat amine is arranged and has the reaction of the aliphatic amide of hydroxyl.Reported the linked reaction of aromatic halogenate and ammoniacal liquor or short-chain alkyl amine in the catalytic aqueous solution of copper sulfate in the European patent EP 0549263.But above-mentioned reaction all can only be carried out at specific compound, thereby can not promote the use of.And (Huang, X. are reacted in the formation of C-N key in the catalytic aqueous solution of Pd of people such as Buchwald report; Anderson, K.W.; Zim, D.; Jiang, L.; Klapars, A.; Buchwald, S.L.J.Am.Chem.Soc.2003,125,6653) then the cost because of catalyst system have defective.The applicant once proposed patent application 200610033067 and 200710026860, had overcome the shortcoming that exists in the conventional art C-N linked reaction method to a certain extent, but also had the too high shortcoming of part consumption.
The present invention is under national 863 high-tech plans classes (2006AA09Z446) are subsidized, and the research that provides a kind of economy, gentleness, eco-friendly N-arylation method to carry out is provided.
Summary of the invention
The object of the present invention is to provide a kind of easy, reaction conditions is gentle, the N-arylation method of environmental friendliness, process economy, overcomes the shortcoming that exists in the C-N linked reaction method in the prior art.
The present invention is the formation method of C-N key in a kind of aqueous solution, with aryl halides and amine is raw material, with water as solvent, in the presence of alkali, reaction or employing traditional heating or microwave-assisted heating under room temperature, add tensio-active agent, under transition metal-catalyzed condition, use the C-N linked reaction of hydrazide kind compound as part.
Innovative point of the present invention is: with the oxide compound of metallic copper or copper or cupprous salt or cupric salt is catalyzer, uses to replace two hydrazide kind compounds as part, can reach effect preferably under the condition of less part consumption.
Involved reaction can adopt following reaction formula to represent among the present invention:
Wherein X-is selected from bromine or iodine.
R
1Be selected from the substituting group of 2-on the aromatic ring or 3-or 4-position, or two on the aromatic ring replaces or multi-substituent; Can be H, NO2 ,-CN ,-COOH ,-COOR, ethanoyl, alkyl, alkoxyl group, aryl, halogen, trifluoromethyl etc. but not only be confined to these substituting groups.
R
2NH
2Being selected from primary amine, can be aromatic amine, aliphatic amide; Comprise that specifically (substituting group is an alkyl to cycloalkyl, benzyl, the substituted benzyl that contains straight or branched alkyl, C5-C7, alkoxyl group etc.) etc. Armeen, or contain the primary amine of aromatic substituent (aromatic substituent is benzene or has alkyl, substituent benzene such as alkoxyl group).
Part is for replacing two hydrazide kind compounds, and its structural formula is:
Wherein R is alkyl or aromatic base; Optional from one of following: as to contain straight or branched alkyl (C1-C6), cycloalkyl, benzyl, benzyl substituting group (substituted alkyl, alkoxyl group, nitro etc.), or (aromatic substituent is benzene or has alkyl to contain aromatic substituent, alkoxyl group, substituent benzene such as nitro).
Concrete reaction process of the present invention is: catalyzer, part, aryl halides, amine, alkali, tensio-active agent and water are added in microwave reactor or the reaction vessel, adopt the mode stirring reaction of microwave-assisted heating or common heating bath heating or direct room temperature reaction; After reaction finished, separating reaction mixed solution and purifying obtained N-arylation product.
Below the inventive method is further described:
(1) with water be reaction solvent, inexpensive, environmental friendliness;
(2) reaction can at room temperature be carried out, and the reaction times is 24-96h, is preferably 48-72h; The reaction heating can be adopted the mode of microwave-assisted heating or common heating bath heating.During the microwave-assisted heating, temperature of reaction is 60-130 ℃, and the reaction times is 1-10min; Preferable reaction temperature is 100-130 ℃, reaction times 2-5min.When common heating bath was heated, temperature of reaction was 50-100 ℃, and the reaction times is 1-24h; Preferable reaction temperature is 60-90 ℃, and the reaction times is 4-16h;
(3) reactant aryl halides can be that replace or non-replacement, and the mol ratio of aryl halides and amine is 1: 1 to 1: 5;
(4) described part is to replace two hydrazide kind compounds; The mol ratio of described part and catalyzer is 10: 1 to 1: 1;
(5) described catalyzer can be the oxide compound of metallic copper, copper, cupprous salt, cupric salt such as cupric oxide, Red copper oxide, copper sulfate, cupric nitrate, cupric chloride, cuprous chloride, cuprous iodide, cupric acetate etc. but be not limited only to that these are several, and the mol ratio of catalyzer and substrate aryl halides is 1: 40 to 1: 2.
(6) described alkali 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 aryl halides is 1: 1 to 3: 1;
(7) employed tensio-active agent can be quaternary ammonium salts, season phosphonium salt class, dodecane sulfonate class, PEG class but not only be confined to these tensio-active agents; The mol ratio of tensio-active agent and substrate aryl halides is 1: 20 to 1: 1.
That the inventive method has is simple to operate, wide application range of substrates, product simply are easy to characteristics such as separation, productive rate height, process economy and environmental friendliness.And because the handiness of reaction conditions, can be according to actual needs, the mode (reaction times is short) of selecting room temperature reaction (energy-conservation, as be adapted to heat-labile substrate, but the reaction times to be longer relatively) accordingly or adopting microwave-assisted to heat.In addition, with water as reaction solvent, with the reacting phase ratio of reporting in the document of the same type, effectively improved the environment friendly of reaction, conform to the requirement of Green Chemistry development more, especially wide application range of substrates is having broad application prospects aspect the preparation of natural product, medicine and agricultural chemicals.
Embodiment
Below in conjunction with embodiment content of the present invention is described further.
Synthesizing of embodiment 1:N-p-methoxyphenyl aniline
With 2mg (0.025mmol) CuO, 48mg (0.125mmol) part, 96mg (0.5mmol) be to the methoxyl group bromobenzene, 279mg (2.0mmol) aniline, 0.28mg (0.5mmol) KOH, 32mg (0.1mmol) TBAB, 5.0ml H
2O adds in the 50ml round-bottomed flask, stirring reaction 96h under the room temperature condition.After reaction stops, use ethyl acetate extraction, washing, the saturated common salt washing behind the anhydrous magnesium sulfate drying, is filtered, underpressure distillation is desolvated, the reaction mixture that obtains is purified by [eluent: petrol ether/ethyl acetate (20: 1)] through the silicagel column column chromatography for separation, gets N-p-methoxyphenyl aniline 83mg, yield 83%.
N-p-methoxyphenyl aniline:
1H NMR (300MHz, CDCl
3) δ: 7.26-7.19 (m, 2H), 7.10 (d, J=8.7,2H), 6.93-6.81 (m, 5H), 5.62 (br s, 1H), 3.81 (s, 3H); MS (ESI, m/z): 200[M+H]
+
Part:
1H NMR (300MHz, CDCl
3) δ: 1.38 (d, J=6.3Hz, 6H), 3.81 (s, 6H), 4.05 (q, J=6.3Hz, 2H), 6.87 (d, J=8.4Hz, 4H), 7.25 (d, family 8.4Hz, 4H).MS(FAB
+，m/z)：387[M+H]
+。
Synthesizing of embodiment 2:N-phenylbenzylamine
With 1.1mg (0.0125mmol) CuCl, 48mg (0.125mmol) part, 96mg (0.5mmol) be to the methoxyl group bromobenzene, 214mg (2.0mmol) benzylamine, 0.56mg (1mmol) KOH, 32mg (0.1mmol) TBAB, 2mlH
2O, 78mg (0.5mmol) bromobenzene adds in the 50ml round-bottomed flask stirring reaction 24h under the room temperature condition.After reaction stops, use ethyl acetate extraction, washing, the saturated common salt washing behind the anhydrous magnesium sulfate drying, is filtered, underpressure distillation is desolvated, the reaction mixture that obtains is purified by [eluent: petrol ether/ethyl acetate (20: 1)] through the silicagel column column chromatography for separation, gets N-phenylbenzylamine 46mg, yield 50%.
The N-phenylbenzylamine:
1H NMR (300MHz, CDCl
3) δ: 7.42-7.41 (and m, 7H), 6.81-6.68 (m, 3H), 4.38 (s, 2H), 4.07 (br s, 1H) .MS (ESI, m/z): 184[M+H]
+
Part:
1H NMR (300MHz, CDCl
3) δ: 1.42 (d,, J=6.6Hz, 6H), 4.11 (q, J=6.6Hz, 2H), 7.27-7.38 (m, 10H).MS(EI，m/z)：326(M
+，4)，105(100)。
Embodiment 3:N-is synthetic to the acetyl phenylbenzylamine
With 47.5mg (0.25mmol) CuI, 104mg (0.25mmol) part, 0.1mg (0.5mmol) be to the acetyl bromobenzene, 214mg (2.0mmol) benzylamine, 212mg (1.0mmol) K
3PO
4, 94mg (0.25mmol) tetraphenylphosphonichloride chloride phosphorus, 5.0ml H
2O adds in the 50ml round-bottomed flask, stirring reaction 24h under 90 ℃ of conditions.After reaction stops, use ethyl acetate extraction, washing, the saturated common salt washing behind the anhydrous magnesium sulfate drying, is filtered, underpressure distillation is desolvated, the reaction mixture that obtains is purified by [eluent: petrol ether/ethyl acetate (10: 1)] through the silicagel column column chromatography for separation, gets N-to acetyl phenylaniline 56mg, yield 50%.
N-is to the acetyl phenylaniline:
1H NMR (400MHz, CDCl
3) δ: 7.83 (d, J=8.8,2H), 7.36-7.30 (m, 5H), 6.61-6.59 (d, J=8.8,2H), 4.41 (s, 2H), 2.49 (s, 3H) .ESI-MS:m/z=226[M+H]
+
Part:
1H NMR (300MHz, CDCl
3) δ: 1.41 (d, J=6.6Hz, 6H), 4.24 (q, J=6.6Hz, 2H), 7.53 (d, J=8.4Hz, 4H), 8.21 (d, J=8.4Hz, 4H), 8.37 (brs, 2H).MS(EI，m/z)：416(M
+，9)，150(100)。
Synthesizing of embodiment 4:N-p-nitrophenyl aniline
With 3.1mg (0.0125mmol) CuSO
45H
2O, 104mg (0.125mmol) part, 100mg (0.5mmol) be to the nitro bromobenzene, 140mg (1.5mmol) aniline, 84mg (1.5mmol) KOH, 161mg (0.5mmol) TBAB, 10ml H
2O adds in the 50ml round-bottomed flask, reflux 10h.After reaction stops, use ethyl acetate extraction, washing, the saturated common salt washing behind the anhydrous magnesium sulfate drying, is filtered, underpressure distillation is desolvated, the reaction mixture that obtains is purified by [eluent: petrol ether/ethyl acetate (10: 1)] through the silicagel column column chromatography for separation, gets N-o-methyl-phenyl-benzylamine 138mg, yield 70%.
N-o-methyl-phenyl-benzylamine:
1H NMR (400MHz, CDCl
3) δ: 8.12 (d, J=9.2,2H), 7.39 (t, J=4.4,2H), 7.22-7.15 (m, 3H), 6.95 (d, J=9.2,2H), 6.30 (br s, 1H) .ESI-MS:m/z=215[M+H]
+
Part:
1H NMR (300MHz, CDCl
3) δ: 4.03 (s, 4H), 7.31-7.39 (m, 10H).ESI-MS：m/z＝299[M+H]
+。
Synthesizing of embodiment 5:N-p-methoxyphenyl n-Butyl Amine 99
With 14mg (0.1mmol) Cu
2O, 54mg (0.2mmol) part, 100mg (0.5mmol) be to the methoxyl group iodobenzene, 118mg (2.5mmol) n-Butyl Amine 99,325mg (1.0mmol) Cs
2CO
3, 136mg (0.5mmol) SDS-Na, 1.5ml H
2O adds in the 8ml microwave reaction pipe, and 80W reacts 10min under 100 ℃ of conditions.After reaction stops, use ethyl acetate extraction, washing, the saturated common salt washing behind the anhydrous magnesium sulfate drying, is filtered, underpressure distillation is desolvated, the reaction mixture that obtains is purified by [eluent: petrol ether/ethyl acetate (20: 1)] through the silicagel column column chromatography for separation, gets N-p-methoxyphenyl n-Butyl Amine 99 45mg, yield 50%.
N-p-methoxyphenyl n-Butyl Amine 99:
1H NMR (400MHz, CDCl
3) δ: 6.81 (d, J=8.8,2H), 6.61 (d, J=8.8,2H), 3.76 (s, 3H), 3.10-3.06 (3H), 1.64-1.57 (m, 2H), 1.48-1.39 (m, 2H), 0.99-0.95 (t, 3H) .ESI-MS:m/z=180[M+H]
+
Part:
1H NMR (300MHz, DMSO-d
6) δ: 6.70-6.75 (m, 6H), 7.13-7.18 (m, 4H), 7.89 (d, J=3Hz, 2H), 10.67 (d, J=3Hz, 2H).MS(EI，m/z)：270(M
+，56)，93(100)。
Embodiment 6:N-p-methoxyphenyl is synthetic to monomethylaniline
With 12.8mg (0.2mmol) Cu, 51mg (0.2mmol) part, 187mg (0.5mmol) be to the methoxyl group bromobenzene, and 53.5mg (0.5mmol) is to monomethylaniline, 84mg (1.5mmol) KOH, 161mg (0.5mmol) TBAB, 10ml H
2O adds in the 50ml round-bottomed flask, reflux 12h.After reaction stops, use ethyl acetate extraction, washing, the saturated common salt washing behind the anhydrous magnesium sulfate drying, is filtered, underpressure distillation is desolvated, the reaction mixture that obtains is purified by [eluent: petrol ether/ethyl acetate (20: 1)] through the silicagel column column chromatography for separation, gets the N-p-methoxyphenyl to methylbenzene 129mg, yield 67%.
1H?NMR(400MHz，CDCl
3)δ：7.06-7.02(m，4H)，6.88-6.84(m，4H)，5.41(br?s，1H)，3.81(s，3H)，2.31(s，3H).ESI-MS：m/z＝214[M+H]
+
Part:
1H NMR (300MHz, CDCl
3) δ: 1.48-1.83 (m, 16H), 3.45-3.52 (m, 2H).ESI-MS：m/z＝255[M+H]
+
Synthesizing of embodiment 7:N-rubigan benzylamine
With 2.3mg (0.0125mmol) Cu (NO
3)
2, 17.6mg (0.0625mmol) part, 96mg (0.5mmol) para chlorobromobenzene, 268mg (2.5mmol) benzylamine, 56mg (1.0mmol) KOH, PEG400 (0.2mL), 1.5ml H
2O adds in the 8ml microwave reaction pipe, and 80W reacts 1min under 130 ℃ of conditions.After reaction stops, use ethyl acetate extraction, washing, the saturated common salt washing behind the anhydrous magnesium sulfate drying, is filtered, underpressure distillation is desolvated, the reaction mixture that obtains is purified by [eluent: petrol ether/ethyl acetate (20: 1)] through the silicagel column column chromatography for separation, gets N-rubigan benzylamine 54mg, yield 50%.
N-rubigan benzylamine:
1H NMR (300MHz, CDCl
3) δ: 7.37-7.26 (m, 5H), 7.14 (d, J=8.7,2H), 6.57 (d, J=8.4,2H), 4.32 (s, 2H), 4.09 (br s, 1H) .ESI-MS:m/z=218[M+H]
+.
Part:
1H NMR (300MHz, CDCl
3) δ: 1.15-1.90 (m, 20H), 2.77-2.85 (m, 2H).ESI-MS：m/z＝：283[M+H]
+
Synthesizing of embodiment 8:N-p-trifluoromethyl phenyl aniline
With 4.5mg (0.025mmol) Cu (OAc)
2, 36mg (0.125mmol) part, 112mg (0.5mmol) be to methyl bromobenzene trifluoride, 214mg (2.0mmol) benzylamine, 138mg (1.0mmol) K
2CO
3, 81mg (0.25mmol) TBAB, 1.5ml H
2O adds in the 8ml microwave reaction pipe, and 80W reacts 7min under 130 ℃ of conditions.After reaction stops, use ethyl acetate extraction, washing, the saturated common salt washing behind the anhydrous magnesium sulfate drying, is filtered, underpressure distillation is desolvated, the reaction mixture that obtains is purified by [eluent: petrol ether/ethyl acetate (20: 1] through the silicagel column column chromatography for separation, N-p-trifluoromethylaniline 71mg, yield 70%.
The N-p-trifluoromethylaniline:
1H NMR (300MHz, CDCl
3) δ: 7.49 (d, J=6.3,2H), 7.10 (t, J=6.3,2H), 7.16 (d, J=5.7,2H), 7.08-7.03 (m, 5H), 5.90 (br s, 1H); ESI-MS:m/z=238[M+H]
+.
Part:
1H NMR (300MHz, CDCl
3) δ: 0.92-1.51 (m, 24H), 2.94-3.01 (m, 2H).ESI-MS：m/z＝287[M+H]
+
Embodiment 9:N-is synthetic to the ethylphenyl benzylamine
With 13.5mg (0.1mmol) CuCl
2, 15mg (0.1mmol) part 85mg (0.5mmol) is to 2 bromo toluene, 321mg (1.5mmol) benzylamine, 69mg (0.5mmol) K
2CO
3, 255mg (0.5mmol) n-hexadecyl three normal-butyl bromination phosphines, 2mlH
2O adds in the 8ml microwave reaction pipe, and 80W reacts 5min under 130 ℃ of conditions.After reaction stops, use ethyl acetate extraction, washing, the saturated common salt washing behind the anhydrous magnesium sulfate drying, is filtered, underpressure distillation is desolvated, the reaction mixture that obtains is purified by [eluent: petrol ether/ethyl acetate (20: 1)] through the silicagel column column chromatography for separation, gets N-o-methyl-phenyl-benzylamine 69mg, yield 70%.
N-is to the ethylphenyl benzylamine:
1H NMR (300MHz, CDCl
3) δ: 7.34-7.17 (m, 5H), 7.06-7.01 (m, 2H), 6.64-6.54 (m, 2H), 4.32 (s, 2H), 3.80 (br s, 1H), 2.12 (s, 3H).
13C NMR (75MHz, CDCl
3) δ: 145.9,139.3,129.9,128.5,127.4,127.1,127.0,121.7,117.0,109.9,48.3,17.6.ESI-MS:m/z=198[M+H]
+
Part:
1H NMR (300MHz, CDCl
3) δ: 10.19 (br s, 2H), 4.99 (br s, 2H), 2.46 (s, 6H) .MS (EI, m/z): 146 (M
+, 80), 46 (100).
Synthesizing of embodiment 9:N-p-methoxyphenyl hexahydroaniline
With 2mg (0.025mmol) CuO, 48mg (0.125mmol) part, 96mg (0.5mmol) be to the methoxyl group bromobenzene, 198mg (2.0mmol) hexahydroaniline, 0.28mg (0.5mmol) KOH, 32mg (0.1mmol) TBAB, 2mlH
2O adds in the 8ml microwave reaction pipe, and 80W reacts 10min under 60 ℃ of conditions.After reaction stops, use ethyl acetate extraction, washing, the saturated common salt washing behind the anhydrous magnesium sulfate drying, is filtered, underpressure distillation is desolvated, the reaction mixture that obtains is purified by [eluent: petrol ether/ethyl acetate (20: 1)] through the silicagel column column chromatography for separation, gets N-p-methoxyphenyl hexahydroaniline 75mg, yield 73%.
N-p-methoxyphenyl hexahydroaniline:
1H NMR (400MHz, CDCl
3) δ: 6.78 (d, J=8.8Hz, 2H), 6.58 (d, J=8.8Hz, 2H), 3.74 (s, 3H), 3.20-3.13 (m, 1H), 2.06-2.02 (m, 2H), 1.78-1.73 (m, 3H), 1.38-1.11 (m, 5H) .ESI-MS:m/z=206[M+H]
+.
Part:
1H NMR (300MHz, CDCl
3) δ: 3.12-3.06 (m, 2H), 2.14-1.51 (m, 28H) .ESI-MS:m/z=387[M+H]
+...
Claims (5)
1. to replace the N-arylation method in the aqueous phase system that two hydrazides are part, with aryl halides and amine is raw material, it is characterized in that: with water as solvent, with the oxide compound of metallic copper or copper or cupprous salt or cupric salt is catalyzer, uses to replace two hydrazide kind compounds and produce the C-N linked reaction as part; Reactions steps is: catalyzer, part, aryl halides, amine, alkali, tensio-active agent and water are added in microwave reactor or the reaction vessel, adopt the mode stirring reaction of microwave-assisted heating or common heating bath heating or direct room temperature reaction; After reaction finished, separating reaction mixed solution and purifying obtained N-arylation product.
2. according to claim 1 to replace the N-arylation method in the aqueous phase system that two hydrazides are part, it is characterized in that: described reaction adopts following reaction formula to represent:
Wherein X-is selected from bromine or iodine;
R
1Be the substituting group of 2-on the aromatic ring or 3-or 4-position, or two on the aromatic ring replaces or multi-substituent; Be selected from one of following: H, NO2 ,-CN ,-COOH ,-COOR, ethanoyl, alkyl, alkoxyl group, aryl, halogen, trifluoromethyl;
R
2NH
2Be primary amine, be aromatic amine or aliphatic amide, be selected from one of following: the Armeen of the cycloalkyl of straight or branched alkyl, C5-C7, benzyl, substituted benzyl; Or contain the primary amine of aromatic substituent;
Part is for replacing two hydrazide kind compounds;
Catalyzer is oxide compound or cupprous salt or cupric salt of metallic copper or copper;
The mol ratio of catalyzer and substrate aryl halides is 1: 40 to 1: 2; The mol ratio of part and catalyzer is 10: 1 to 1: 1.
3. according to claim 1 and 2 to replace the N-arylation method in the aqueous phase system that two hydrazides are part, it is characterized in that: described part is a substituted hydrazide compound, and its structural formula is:
4. according to claim 1 and 2 to replace the N-arylation method in the aqueous phase system that hydrazides is a part, it is characterized in that: described catalyzer is selected from one of following; Metallic copper, cupric oxide, Red copper oxide, copper sulfate, cupric nitrate, cupric chloride, cuprous chloride, cuprous iodide, cupric acetate.
5. according to claim 1 and 2 to replace the N-arylation method in the aqueous phase system that two hydrazides are part, it is characterized in that: the mol ratio of aryl halides and amine is 1: 1 to 1: 5.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200910040649 CN101691318B (en) | 2009-06-29 | 2009-06-29 | N-arylation method taking substituted adipic dihydrazide as ligand in aqueous phase system |
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| CN 200910040649 CN101691318B (en) | 2009-06-29 | 2009-06-29 | N-arylation method taking substituted adipic dihydrazide as ligand in aqueous phase system |
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| CN101691318B CN101691318B (en) | 2013-05-29 |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102050687A (en) * | 2010-11-30 | 2011-05-11 | 中山大学 | Method for preparing aromatic primary amine by taking ammonia water as ammonia source in water phase system |
| CN102806104A (en) * | 2012-08-21 | 2012-12-05 | 浙江大学 | Catalyst for aqueous-phase preparation of indole nitrogen arylide and preparation method of indole nitrogen arylide |
| CN106883132A (en) * | 2017-01-18 | 2017-06-23 | 中山大学 | With N, the substitution hydrazides of N bis- is the copper catalysis C N coupling methods of part to one kind |
| CN109456205A (en) * | 2018-12-17 | 2019-03-12 | 石河子大学 | Using substd quinolines or isoquinolin hydrazides pyridine-N-oxides as the N- arylation method in the aqueous phase system of ligand |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090012300A1 (en) * | 2004-07-16 | 2009-01-08 | Mathilda Maria Henrica Lambers | Process for the Preparation of an (Hetero) Arylamine |
| CN100336794C (en) * | 2006-01-19 | 2007-09-12 | 中山大学 | N-arylation process with hydrazone as ligand in aqueous phase system |
| CN101012170B (en) * | 2007-02-09 | 2010-12-08 | 中山大学 | N-arylation method in water solution |
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2009
- 2009-06-29 CN CN 200910040649 patent/CN101691318B/en active Active
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102050687A (en) * | 2010-11-30 | 2011-05-11 | 中山大学 | Method for preparing aromatic primary amine by taking ammonia water as ammonia source in water phase system |
| CN102050687B (en) * | 2010-11-30 | 2014-04-23 | 中山大学 | Method for preparing aromatic primary amine by taking ammonia water as ammonia source in water phase system |
| CN102806104A (en) * | 2012-08-21 | 2012-12-05 | 浙江大学 | Catalyst for aqueous-phase preparation of indole nitrogen arylide and preparation method of indole nitrogen arylide |
| CN102806104B (en) * | 2012-08-21 | 2015-01-21 | 浙江大学 | Catalyst for aqueous-phase preparation of indole nitrogen arylide and preparation method of indole nitrogen arylide |
| CN106883132A (en) * | 2017-01-18 | 2017-06-23 | 中山大学 | With N, the substitution hydrazides of N bis- is the copper catalysis C N coupling methods of part to one kind |
| 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- |
| CN109456205A (en) * | 2018-12-17 | 2019-03-12 | 石河子大学 | Using substd quinolines or isoquinolin hydrazides pyridine-N-oxides as the N- arylation method in the aqueous phase system of ligand |
| CN109456205B (en) * | 2018-12-17 | 2021-09-21 | 石河子大学 | N-arylation method in aqueous phase system by using substituted quinoline or isoquinoline hydrazide pyridine-N-oxide as ligand |
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