CN103342651A - Synthesis method of diaryl aniline compound - Google Patents
Synthesis method of diaryl aniline compound Download PDFInfo
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- CN103342651A CN103342651A CN2013103127993A CN201310312799A CN103342651A CN 103342651 A CN103342651 A CN 103342651A CN 2013103127993 A CN2013103127993 A CN 2013103127993A CN 201310312799 A CN201310312799 A CN 201310312799A CN 103342651 A CN103342651 A CN 103342651A
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Abstract
The invention relates to a synthesis method of a diaryl aniline compound. The method comprises steps of with copper acetylacetonate (Cu(acac)2) as a catalyst, enabling a nitrobenzene compound to react with a phenylboronic acid compound in an organic solvent in the presence of alkali, thus preparing the diaryl aniline compound. The method has the advantages of high product yield, high purity, simple reaction, simpleness and convenience for operation, short reaction duration and the like, thus providing a brand-new synthesis method for preparation of like compounds; and the synthesis method has a good industrialization prospect and a potential application value.
Description
Technical field
The present invention relates to a kind of synthetic method of aminated compounds, relate to a kind of synthetic method of diaryl aniline compound especially, belong to the organic chemical synthesis field.
Background technology
Aromatic amine is the very important organic and pharmaceutical intermediate of a class, is widely used in synthesizing of the part that uses in the synthetic and transition-metal catalysis of Yi Yao ﹑ Nong Yao ﹑ dyestuff.For its synthetic method, the Buchwald-Hartwig cross-coupling reaction is the important method of synthetic aroma aminated compounds, but employed complicated part or halohydrocarbon environmental pollution as substrate is bigger in this method, and this has greatly limited promoting the use of of this method.
On the basis of above-mentioned defective, people have developed the operational path that uses aryl boric acid, because aryl boric acid has low toxicity, working conditions gentleness, stable to water and air, and plurality of advantages such as the substrate scope is wide, functional group's tolerance is good and be subjected to extensive concern in the organic synthesis field.
1998, people such as Chan disclosed the C-N linked reaction that copper catalysis aryl boric acid participates in, and described reaction can at room temperature be carried out, and is applicable to aliphatic amide, aromatic amine, imines, urea, carbamate, sulphonamide etc.Its reaction formula is as follows:
Calendar year 2001, people such as Collman have realized [Cu (OH) TMEDA] under the water condition
2Cl
2The C-N linked reaction of the aryl boric acid under the catalysis and imidazoles, described reaction conditions gentleness need not to add in addition alkali, and defective is that the productive rate of product is medium, and utilising efficiency is not high.Its reaction formula is as follows:
People such as Antilla disclose the linked reaction that can realize copper catalysis aryl boric acid and nitrogenous compound under air conditions, and described method has also used 2,6-lutidine as alkali, and its reaction formula is as follows:
People such as Biffis utilized Cu (OAc) in 2003
2Functional resin MPI – Cu (1:1) the catalysis aryl boric acid of exchange and the C-N linked reaction of arylamine, described method can be finished under room temperature, air and alkali-free participation condition, but defective is that the productive rate that reacts is unsatisfactory, the substrate scope is also very narrow.Its reaction formula is as follows:
2004, people such as Das disclosed under microwave-assisted, the aryl boric acid of KF-alumina surface copper catalysis and the C-N linked reaction of arylamine, and its reaction formula is as follows:
2005, people such as Hari reported the linked reaction of 3-trimethyl silane benzoglyoxaline and aryl boric acid under the copper catalysis, and this method has optionally been synthesized 1-aryl-3-trimethyl silane benzoglyoxaline.By the KOH/EtOH hydrolysis, obtain 1-aryl benzoglyoxaline then, its reaction formula is as follows:
People such as Kantam disclose the hydrotalcite catalyzed imide of a kind of Cu-A and aryl boric acid linked reaction, and described method namely can realize under the room temperature in methanol solvate, need not to add part and alkali in the reaction, and catalyzer can recycle.Its reaction formula is as follows:
2006, people such as Kantam utilized callable Cu (OAc)
2H
2O/[bmim] [BF
4] catalyst system, the C-N linked reaction of realization aryl boric acid and imidazoles, imines, amine, acid amides, sulphonamide, its reaction formula is as follows:
People such as Kantam are catalyzer with CuFAP, have realized the C-N linked reaction of aryl boric acid and imidazoles, arylamine and aliphatic amide under the no alkali systems, and substrate scope and the productive rate of reaction all have result preferably, and its reaction formula is as follows:
2008, people such as Chen were developed the aryl boric acid of copper catalysis under the microwave-assisted and the linked reaction of amine, and described being reflected in the DMSO solution is alkali with DBU, and its reaction formula is as follows:
People such as Zheng utilize Cu (OTf)
2/ EtOH catalyst system has been realized the linked reaction of aryl boric acid acid anhydride and imidazoles, imines, amine, acid amides, sulphonamide, and its reaction formula is as follows:
People such as Tao have carried out systematic study to the linked reaction of copper catalysis aryl boric acid and nitrogen heterocyclic ring amine, by utilizing dry TMEDA, as mixed solvent, have realized at room temperature that optionally carbon-nitrogen forms linked reaction with the first alcohol and water, and its reaction formula is as follows:
2009, people such as Singh reported in the microreactor of continuous flow, in composite catalyst system Cu (OAc)
2/ Et
3Linked reaction under the catalysis of N/ pyridine, its reaction formula is as follows:
2010, people such as Liu were catalyzer with Cu-NHC, had suffered the linked reaction that realizes aryl boric acid and benzoglyoxaline at methyl alcohol, and defective is that arylamine and aryl boric acid only obtain moderate yield, and aliphatic amide is reaction hardly then, and its reaction formula is as follows:
2011, people such as Islam were developed Cu (the II)-PAR catalyzer of the callable polymkeric substance load of a class, had realized the C-N linked reaction of aryl boric acid in methyl alcohol under 40 ℃, and its reaction formula is as follows:
People such as Kaboudin are catalyzer with the Cu (II) of beta-cyclodextrin complexing, add under part and the alkali condition in nothing, have realized the linked reaction of aryl boric acid and primary amine in empty G﹠W, and its reaction formula is as follows:
2012, people such as Molaei were with Cu (OAc)
2Be catalyzer, the n-Bu 20%
4Realized the C-N linked reaction in the NOH solvent, its reaction formula is as follows:
People such as Raghuvanshi have reported the Chan-Lam reaction of aryl boric acid and the nitrogenous compound of nickel catalysis, and its reaction formula is as follows:
As mentioned above, disclose the method for multiple synthesizing aryl aniline in the prior art, but still there are some defectives in these methods, can only be substrate with the aminocompound for example, and this has limited the expansion of substrate greatly; Perhaps reactions steps too much and in the system material quantity too much etc., these have all limited the productive rate of final purpose product.
Therefore, for a kind of easy, efficient, eco-friendly method for preparing aryl aniline of exploitation, being still the active demand in the present organic synthesis field, also is one of the research focus and emphasis in this field at present, especially the power place that is accomplished of the present invention.
Summary of the invention
In order to overcome above-mentioned pointed many defectives, simultaneously in view of the vital role of aromatic amine in organic synthesis, develop a kind of efficient, gentle catalyst system, directly by be simple and easy to nitro-aromatic and fragrant boric acid react and the diversified aromatic amine derivant of composite structure, this is also significant in actual applications not only in theory.In order to seek the short-cut method of synthesis of diaryl aniline, the inventor has carried out deep research, after having paid a large amount of creative works, find that but copper source catalyzer and alkali exist down, in solvent by nitro-aromatic and aromatic yl acid reaction and a step obtains the diaryl aniline compound, thereby finished the present invention.
Particularly, technical scheme of the present invention and content relate to the synthetic method of diaryl aniline compound shown in a kind of following formula (I);
Described method comprises: with acetylacetone copper (Cu (acac)
2) be catalyzer, in the presence of alkali and in organic solvent, formula (II) nitrobenzene compound and formula (III) phenylo boric acid compound are reacted, thus the diaryl aniline compound of the formula of making (I);
R wherein
1Be selected from H, halogen, aldehyde radical, C independently of one another
1-C
6Alkyl, C
1-C
6Alkoxyl group, halo C
1-C
6Alkyl or halo C
1-C
6Alkoxyl group;
R
2Be selected from H, halogen, C independently of one another
1-C
6Alkyl, C
1-C
6Alkoxyl group, halo C
1-C
6Alkyl or halo C
1-C
6Alkoxyl group.
In described synthetic method of the present invention, unless otherwise prescribed, from start to finish, C
1-C
6The implication of alkyl refers to have the straight or branched alkyl of 1-6 carbon atom, and it has comprised C
1Alkyl, C
2Alkyl, C
3Alkyl, C
4Alkyl, C
5Alkyl or C
6Alkyl for example can be to indefiniteness methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, sec-butyl, isobutyl-, the tertiary butyl, n-pentyl, isopentyl or n-hexyl etc.
In the present invention, unless otherwise prescribed, from start to finish, C
1-C
6Alkoxyl group refers to above-mentioned definition " C
1-C
6Alkyl " with group after the O atom links to each other.
In the present invention, unless otherwise prescribed, from start to finish, halo C
1-C
6The implication of alkyl refers to the " C of the above-mentioned definition that replaced by halogen
1-C
6Alkyl ", for example be trifluoromethyl, pentafluoroethyl group, difluoromethyl, chloromethyl etc. indefiniteness.
In the present invention, unless otherwise prescribed, from start to finish, halo C
1-C
6The implication of alkoxyl group refers to the " C of the above-mentioned definition that replaced by halogen
1-C
6Alkoxyl group ", for example be to indefiniteness trifluoromethoxy, five fluorine oxyethyl groups, difluoro-methoxy, chlorine methoxyl group etc.
In the present invention, unless otherwise prescribed, from start to finish, the implication of " halogen " refers to haloid element, non-exclusively for example can be F, Cl, Br or I.
In described synthetic method of the present invention, described alkali be selected from alkali metal hydroxide, the alkali metal alcoholates any one or multiple.
Wherein, described alkali-metal oxyhydroxide for example is LiOH, NaOH, KOH or CsOH, and described alkali alcoholate for example is sodium methylate, potassium methylate, sodium ethylate, potassium ethylate, sodium tert-butoxide or potassium tert.-butoxide.Be described alkali be in LiOH, NaOH, KOH, CsOH, sodium methylate, potassium methylate, sodium ethylate, potassium ethylate, sodium tert-butoxide or the potassium tert.-butoxide any one or multiple arbitrarily.
Described alkali is preferably alkali alcoholate, most preferably is potassium tert.-butoxide.
In described synthetic method of the present invention, described organic solvent is selected from toluene, dimethylbenzene, chlorobenzene, dimethyl sulfoxide (DMSO) (DMSO), tetrahydrofuran (THF) (THF), 1, and any or multiple in the 4-dioxane most preferably is 1,4-dioxane.
In described synthetic method of the present invention, formula (II) is 1:2-4 with (III) mol ratio of compound, for example can be 1:2,1:2.5,1:3,1:3.5 or 1:4.
In described synthetic method of the present invention, the mol ratio of formula (II) compound and acetylacetone copper is 1:0.05-0.2, for example is 1:0.05,1:0.1,1:0.15 or 1:0.2.
In described synthetic method of the present invention, the mol ratio of formula (II) compound and alkali is 1:2-6, for example is 1:2,1:2.5,1:3,1:3.5,1:4,1:4.5,1:5,1:5.5 or 1:6.
In described synthetic method of the present invention, temperature of reaction is 80-140 ℃, for example can be to indefiniteness 80 ℃, 90 ℃, 100 ℃, 110 ℃, 120 ℃, 130 ℃ or 140 ℃.
In described synthetic method of the present invention, reaction times there is no special restriction, for example can how much determine the suitable reaction times by the residual quantity of liquid chromatography or TLC detection raw material, it typically is 10-14 hour, for example is 10 hours, 10.5 hours, 11 hours, 11.5 hours, 12 hours, 12.5 hours, 13 hours, 13.5 hours or 14 hours indefiniteness.
In described synthetic method of the present invention, reaction of the present invention is preferably carried out under protection of inert gas, and described rare gas element for example can be nitrogen.
In described synthetic method of the present invention, select a kind of of preferred implementation to give an example as some key element, can be as follows:
Formula (II) is 1:3 with the mol ratio of formula (III) compound, and/or
The mol ratio of formula (II) compound and acetylacetone copper is 1:0.1, and/or
The mol ratio of formula (II) compound and alkali is 1:4, and/or
Organic solvent is 1,4-dioxane, and/or
Temperature of reaction is 110 ℃, and/or
Reaction times is 12 hours, and/or
Be reflected under the nitrogen protection and carry out.
In described synthetic method of the present invention, aftertreatment after reaction finishes can be adopted any known conventional processing means in the organic synthesis field, any processing means in for example crystallization, recrystallization, column chromatography purification, the extraction etc. or the combination of multiple processing means.As a kind of exemplary aftertreatment means, for example can be: after reaction finishes, filter, desolventizing the mixture that after reaction finishes, obtains with Rotary Evaporators, residue is crossed 200-500 order silica gel column chromatography and is purified and obtain target product, but column chromatography process TLC tracing and monitoring and determine suitable wash-out terminal point.
As a kind of exemplary exemplifying, R
1Can be H, chlorine, methyl, methoxyl group, aldehyde radical.
As a kind of exemplary exemplifying, R
2Can be H, F, Cl, Br, methyl, the tertiary butyl, methoxyl group.
Described synthetic method of the present invention in organic solvent, is reacted nitrobenzene compound and phenylo boric acid compound, thereby is made the diaryl aniline compound in the presence of alkali by using acetylacetone copper as catalyzer.Plurality of advantages such as described method has product yield height, purity height, reaction is simple, easy and simple to handle, the reaction times is short, thus for the preparation of this compounds provides brand-new synthetic method, have excellent industrial application foreground and potential using value.
Embodiment
The present invention is described in detail below by specific embodiment; but the purposes of these exemplary embodiments and purpose only are used for exemplifying the present invention; be not that real protection scope of the present invention is constituted any type of any restriction, more non-protection scope of the present invention be confined to this.
Embodiment 1: pentanoic synthetic
In the flask of dried and clean, add 50ml solvent 1, the 4-dioxane adds following formula (II) compound, formula (III) compound, Cu (acac) then successively
2And potassium tert.-butoxide, making its mol ratio is 1:2:0.05:2, its Chinese style (II) compound is 10mmol, nitrogen replacement three times continue to feed under the protection of nitrogen gas then, with reaction system 80 ℃ of following stirring reactions 14 hours.
After reaction finishes, filter, use Rotary Evaporators with desolventizing filtrate, residue is crossed 200-300 order silica gel column chromatography and is purified, and obtains the target product into solid, and productive rate is 98.2%, and purity is 98.9% (HPLC).
Fusing point: 52-53 ℃;
Nucleus magnetic resonance:
1H NMR (CDCl
3, 500MHz): δ 7.23-7.26 (m, 4H), 7.04-7.09 (m, 4H), 6.93 (m, 2H), 5.69 (s, 1H);
13C?NMR(CDCl
3,125MHz)δ143.2(2C),129.4(4C),121.0(4C),117.8(2C)。
Embodiment 2: tolyl-amine is synthetic between phenyl
In the flask of dried and clean, add 50ml solvent 1, the 4-dioxane adds following formula (II) compound, formula (III) compound, Cu (acac) then successively
2And potassium tert.-butoxide, making its mol ratio is 1:3:0.1:3, its Chinese style (II) compound is 10mmol, nitrogen replacement three times continue to feed under the protection of nitrogen gas then, with reaction system 90 ℃ of following stirring reactions 13 hours.
After reaction finishes, filter, use Rotary Evaporators with desolventizing filtrate, residue is crossed 300-400 order silica gel column chromatography and is purified, and obtains target product, and productive rate is 95.3%, and purity is 98.2% (HPLC).
Nucleus magnetic resonance:
1H NMR (CDCl
3, 500MHz): δ 7.27-7.24 (m, 2H), 7.15 (t, J=7.9Hz, 1H), 7.06 (d, J=7.7Hz, 2H), 6.93-6.88 (m, 3H), 6.75 (d, J=7.5Hz, 1H), 5.73 (s, 1H), 2.31 (s, 3H);
13C?NMR(CDCl
3,125MHz)δ143.2,143.1,139.2,129.3(2C),129.1,121.9,120.9(2C),118.6,117.9,115.0,21.5。
Embodiment 3: phenyl p-methoxyphenyl-amine synthetic
In the flask of dried and clean, add 50ml solvent 1, the 4-dioxane adds following formula (II) compound, formula (III) compound, Cu (acac) then successively
2And potassium tert.-butoxide, making its mol ratio is 1:4:0.15:4, its Chinese style (II) compound is 10mmol, nitrogen replacement three times continue to feed under the protection of nitrogen gas then, with reaction system 100 ℃ of following stirring reactions 12 hours.
After reaction finishes, filter, use Rotary Evaporators with desolventizing filtrate, residue is crossed 400-500 order silica gel column chromatography and is purified, and obtains target product, and productive rate is 96.4%, and purity is 99.1% (HPLC).
Nucleus magnetic resonance:
1H NMR (CDCl
3, 500MHz): δ 7.21-7.27 (m, 2H), 7.07-7.11 (m, 2H), 6.95-6.84 (m, 5H), 5.52 (s, 1H), 3.83 (s, 3H);
13C?NMR(CDCl
3,125MHz)δ144.0,140.3,130.9,129.9(2C),129.3(2C),120.3(2C),118.9,116.9(2C),29.7。
Embodiment 4: phenyl rubigan-amine synthetic
In the flask of dried and clean, add 50ml solvent 1, the 4-dioxane adds following formula (II) compound, formula (III) compound, Cu (acac) then successively
2And potassium tert.-butoxide, making its mol ratio is 1:2.5:0.2:5, its Chinese style (II) compound is 10mmol, nitrogen replacement three times continue to feed under the protection of nitrogen gas then, with reaction system 110 ℃ of following stirring reactions 11 hours.
After reaction finishes, filter, use Rotary Evaporators with desolventizing filtrate, residue is crossed 200-300 order silica gel column chromatography and is purified, and obtains target product, and productive rate is 94.9%, and purity is 98.3% (HPLC).
Nucleus magnetic resonance:
1H NMR (CDCl
3, 500MHz): δ 7.22-7.29 (m, 2H), 7.16-7.21 (m, 2H), 7.00-7.06 (m, 2H), 6.97-6.93 (m, 3H), 5.53 (s, 1H);
13C?NMR(CDCl
3,125MHz)δ142.7,141.9,129.5(2C),129.3(2C),125.6,121.6(2C),118.9(2C),118.2。
Embodiment 5: phenyl is synthetic to aldehyde radical phenyl-amine
In the flask of dried and clean, add 50ml solvent 1, the 4-dioxane adds following formula (II) compound, formula (III) compound, Cu (acac) then successively
2And potassium tert.-butoxide, making its mol ratio is 1:3.5:0.05:6, its Chinese style (II) compound is 10mmol, nitrogen replacement three times continue to feed under the protection of nitrogen gas then, with reaction system 120 ℃ of following stirring reactions 10 hours.
After reaction finishes, filter, use Rotary Evaporators with desolventizing filtrate, residue is crossed 300-400 order silica gel column chromatography and is purified, and obtains target product, and productive rate is 93.8%, and purity is 98.6% (HPLC).
Nucleus magnetic resonance:
1H NMR (CDCl
3, 500MHz): δ 9.78 (s, 1H), 7.70-7.79 (m, 2H), 7.33-7.38 (m, 2H), 7.18-7.23 (m, 2H), 7.12-7.16 (m, 1H), 7.00-7.04 (m, 2H), 6.22 (s, 1H);
13C?NMR(CDCl
3,125MHz)δ190.4,149.7,139.9,132.1(2C),129.5(2C),128.5,123.8(2C),121.2(2C),114.4。
Embodiment 6: tolyl-amine is synthetic between phenyl
In the flask of dried and clean, add 50ml solvent 1, the 4-dioxane adds following formula (II) compound, formula (III) compound, Cu (acac) then successively
2And potassium tert.-butoxide, making its mol ratio is 1:2:0.2:2, its Chinese style (II) compound is 10mmol, nitrogen replacement three times continue to feed under the protection of nitrogen gas then, with reaction system 130 ℃ of following stirring reactions 10.5 hours.
After reaction finishes, filter, use Rotary Evaporators with desolventizing filtrate, residue is crossed 400-500 order silica gel column chromatography and is purified, and obtains target product, and productive rate is 89.9%, and purity is 98.3% (HPLC).
Nucleus magnetic resonance:
1H NMR (CDCl
3, 500MHz): δ 7.27-7.24 (m, 2H), 7.15 (t, J=7.9Hz, 1H), 7.06 (d, J=7.7Hz, 2H), 6.93-6.88 (m, 3H), 6.75 (d, J=7.5Hz, 1H), 5.73 (s, 1H), 2.31 (s, 3H);
13C?NMR(CDCl
3,125MHz)δ143.2,143.1,139.2,129.3(2C),129.1,121.9,120.9(2C),118.6,117.9,115.0,21.5。
Embodiment 7: phenyl m-methoxyphenyl-amine synthetic
In the flask of dried and clean, add 50ml solvent 1, the 4-dioxane adds following formula (II) compound, formula (III) compound, Cu (acac) then successively
2And potassium tert.-butoxide, making its mol ratio is 1:4:0.1:4.5, its Chinese style (II) compound is 10mmol, nitrogen replacement three times continue to feed under the protection of nitrogen gas then, with reaction system 140 ℃ of following stirring reactions 11.5 hours.
After reaction finishes, filter, use Rotary Evaporators with desolventizing filtrate, residue is crossed 200-300 order silica gel column chromatography and is purified, and obtains target product, and productive rate is 90.2%, and purity is 97.9% (HPLC).
1H?NMR(CDCl
3,500MHz):δ7.12-7.07(m,3H),6.80-6.86(m,2H),6.49-6.46(m,2H),6.34-6.40(m,1H),5.53(s,1H),3.79(s,3H),3.75(s,3H)；
13C?NMR(CDCl
3,125MHz)δ160.8,155.5,146.7,135.5,130.1,122.8(2C),114.7(2C),108.4,104.8,101.4,55.6,55.2。
Embodiment 8: phenyl is synthetic to fluorophenyl-amine
In the flask of dried and clean, add 50ml solvent 1, the 4-dioxane adds following formula (II) compound, formula (III) compound, Cu (acac) then successively
2And potassium tert.-butoxide, making its mol ratio is 1:2.5:0.15:2.5, its Chinese style (II) compound is 10mmol, nitrogen replacement three times continue to feed under the protection of nitrogen gas then, with reaction system 85 ℃ of following stirring reactions 13.5 hours.
After reaction finishes, filter, use Rotary Evaporators with desolventizing filtrate, residue is crossed 300-400 order silica gel column chromatography and is purified, and obtains target product, and productive rate is 91.2%, and purity is 98.4% (HPLC).
Nucleus magnetic resonance:
1H NMR (CDCl
3, 500MHz): δ 7.19-7.25 (m, 2H), 7.05-7.03 (m, 2H), 6.98-6.95 (m, 4H), 6.86-6.89 (m, 1H), 5.55 (s, 1H);
13C?NMR(CDCl
3,125MHz)δ158.1(d,
1J
C-F=238.7Hz,1C),143.9,138.9,129.4(2C),120.6(2C),119.7(2C),116.9,115.9(d,J
C-F=22.4Hz,2C)。
Embodiment 9: phenyl is synthetic to tert-butyl-phenyl-amine
In the flask of dried and clean, add 50ml solvent 1, the 4-dioxane adds following formula (II) compound, formula (III) compound, Cu (acac) then successively
2And potassium tert.-butoxide, making its mol ratio is 1:3.5:0.05:5.5, its Chinese style (II) compound is 10mmol, nitrogen replacement three times continue to feed under the protection of nitrogen gas then, with reaction system 95 ℃ of following stirring reactions 12.5 hours.
After reaction finishes, filter, use Rotary Evaporators with desolventizing filtrate, residue is crossed 400-500 order silica gel column chromatography and is purified, and obtains target product, and productive rate is 90.5%, and purity is 97.7% (HPLC).
Nucleus magnetic resonance:
1H NMR (CDCl
3, 500MHz): δ 7.29 (d, J=8.7Hz, 2H), 7.25-7.22 (m, 2H), 7.04-7.02 (m, 4H), 6.88 (t, J=7.1Hz, 1H), 5.65 (s, 1H), 1.31 (s, 9H);
13C?NMR(CDCl
3,125MHz)δ144.2,143.7,140.3,129.3(2C),126.1(2C),120.4(2C),118.2(2C),117.2,34.1,31.5(3C)。
Embodiment 10: tolyl-amine is synthetic between p-methoxyphenyl
In the flask of dried and clean, add 50ml solvent 1, the 4-dioxane adds following formula (II) compound, formula (III) compound, Cu (acac) then successively
2And potassium tert.-butoxide, making its mol ratio is 1:2:0.1:6, its Chinese style (II) compound is 10mmol, nitrogen replacement three times continue to feed under the protection of nitrogen gas then, with reaction system 105 ℃ of following stirring reactions 10.5 hours.
After reaction finishes, filter, use Rotary Evaporators with desolventizing filtrate, residue is crossed 200-300 order silica gel column chromatography and is purified, and obtains target product, and productive rate is 91.2%, and purity is 97.9% (HPLC).
Nucleus magnetic resonance:
1H NMR (CDCl
3, 500MHz): δ 7.23-7.25 (m, 1H), 7.07-7.10 (m, 1H), 7.03-7.55 (m, 2H), 6.83-6.87 (m, 1H), 6.70-6.72 (m, 2H), 6.64-6.67 (m, 1H), 5.43 (s, 1H), 3.79 (s, 3H), 2.27 (s, 3H);
13C?NMR(CDCl
3,125MHz)δ155.2,145.2,139.2,135.9,129.2(2C),122.2,120.5,116.4,114.7,112.9(2C),55.6,21.6。
Embodiment 11: to synthesizing of fluorophenyl p-methoxyphenyl-amine
In the flask of dried and clean, add 50ml solvent 1, the 4-dioxane adds following formula (II) compound, formula (III) compound, Cu (acac) then successively
2And potassium tert.-butoxide, making its mol ratio is 1:3:0.2:2, its Chinese style (II) compound is 10mmol, nitrogen replacement three times continue to feed under the protection of nitrogen gas then, with reaction system 80 ℃ of following stirring reactions 14 hours.
After reaction finishes, filter, use Rotary Evaporators with desolventizing filtrate, residue is crossed 300-400 order silica gel column chromatography and is purified, and obtains target product, and productive rate is 88.9%, and purity is 98.0% (HPLC).
Nucleus magnetic resonance:
1H NMR (CDCl
3, 500MHz): δ 7.00-7.03 (m, 2H), 6.86-6.97 (m, 6H), 5.40 (s, 1H), 3.81 (s, 3H);
13C?NMR(CDCl
3,125MHz)δ156.9(d,
1J
C-F=237.7Hz,1C),154.8,140.9136.4,121.0(2C),117.6(2C),115.6(d,J=22.4Hz,2C),114.6(2C),55.5.
Embodiment 12: tolyl-amine is synthetic between rubigan
In the flask of dried and clean, add 50ml solvent 1, the 4-dioxane adds following formula (II) compound, formula (III) compound, Cu (acac) then successively
2And potassium tert.-butoxide, making its mol ratio is 1:4:0.1:5, its Chinese style (II) compound is 10mmol, nitrogen replacement three times continue to feed under the protection of nitrogen gas then, with reaction system 90 ℃ of following stirring reactions 10 hours.
After reaction finishes, filter, use Rotary Evaporators with desolventizing filtrate, residue is crossed 400-500 order silica gel column chromatography and is purified, and obtains target product, and productive rate is 88.3%, and purity is 98.9% (HPLC).
Nucleus magnetic resonance:
1H NMR (CDCl
3, 500MHz): δ 7.19-7.21 (m, 2H), 7.15-7.17 (m, 2H), 6.96-6.99 (m, 1H), 6.85-6.87 (m, 2H), 6.75-6.79 (m, 1H), 5.71 (s, 1H), 2.32 (s, 3H);
13C?NMR(CDCl
3,125MHz)δ142.7,142.0,139.5,129.4(2C),129.3,125.6,123.4,122.6(2C),119.0,118.7,22.3。
Embodiment 13: tolyl-amine is synthetic between guaiacyl
In the flask of dried and clean, add 50ml solvent 1, the 4-dioxane adds following formula (II) compound, formula (III) compound, Cu (acac) then successively
2And potassium tert.-butoxide, making its mol ratio is 1:2:0.2:4, its Chinese style (II) compound is 10mmol, nitrogen replacement three times continue to feed under the protection of nitrogen gas then, with reaction system 100 ℃ of following stirring reactions 10 hours.
After reaction finishes, filter, use Rotary Evaporators with desolventizing filtrate, residue is crossed 200-300 order silica gel column chromatography and is purified, and obtains target product, and productive rate is 98.1%, and purity is 98.8% (HPLC).
Nucleus magnetic resonance:
1H NMR (CDCl
3, 500MHz): δ 7.28-7.30 (m, 2H), 7.14-7.17 (m, 3H), 6.94-6.96 (m, 2H), 6.73-6.76 (m, 1H), 6.10 (s, 1H), 3.86 (s, 3H), 2.31 (s, 3H);
13C?NMR(CDCl
3,125MHz)δ148.3,142.7,139.1,133.1,129.1,122.0,120.8,119.8,119.3,115.7,114.8,110.5,55.6,21.6。
Embodiment 14: guaiacyl is synthetic to fluorophenyl-amine
In the flask of dried and clean, add 50ml solvent 1, the 4-dioxane adds following formula (II) compound, formula (III) compound, Cu (acac) then successively
2And potassium tert.-butoxide, making its mol ratio is 1:2.5:0.1:5.5, its Chinese style (II) compound is 10mmol, nitrogen replacement three times continue to feed under the protection of nitrogen gas then, with reaction system 110 ℃ of following stirring reactions 11 hours.
After reaction finishes, filter, use Rotary Evaporators with desolventizing filtrate, residue is crossed 300-400 order silica gel column chromatography and is purified, and obtains target product, and productive rate is 95.8%, and purity is 98.0% (HPLC).
Nucleus magnetic resonance:
1H NMR (CDCl
3, 500MHz): δ 7.08-7.12 (m, 3H), 6.96-6.99 (m, 2H), 6.82-6.88 (m, 3H), 6.03 (s, 1H), 3.88 (s, 3H);
13C?NMR(CDCl
3,125MHz)δ158.1(d,
1J
C-F=238.7Hz,1C),147.8,138.6,133.7,121.2,120.8(2C),119.5,115.8(d,J=22.3Hz,2C),113.6,110.4,55.5.
Can be found out by above-described embodiment 1-14, when adopting described method of the present invention, can obtain the diaryl aniline compound with high yield, high purity, have favorable industrial using value and research prospect.
Embodiment 15-28
Except acetylacetone copper is wherein replaced with the following copper compound, implemented embodiment 15-28 respectively in the mode identical with embodiment 1-14, the yield of the copper compound that uses, embodiment corresponding relation and corresponding product is as shown in the table.
As seen from the above table, when using other copper compound, reaction or at all can't carry out, or productive rate sharply reduces, and this proves Cu used in the present invention (acac)
2Has specific catalysis specificity for this reaction.
Embodiment 29-42
Except the solvent 1 of inciting somebody to action wherein, the 4-dioxane replaces with respectively outside the following solvent, has implemented embodiment 29-42 respectively in the mode identical with embodiment 1-14, and the yield of the solvent that uses, embodiment corresponding relation and corresponding product is as shown in the table.
As seen from the above table, when using other solvent, for example when using DMSO, chlorine benzene,toluene,xylene, THF, reaction can be carried out equally, but productive rate reduces significantly.And when for acetonitrile, DMF, methylene dichloride, tetracol phenixin, ethanol, the trimethyl carbinol, PEG-400, benzene, then reaction can't be carried out at all.
Can find out also simultaneously that when adopting benzene to be solvent, reaction can't be carried out, and when using chlorobenzene, toluene or dimethylbenzene, then reaction can be carried out smoothly, this has proved that solvent has remarkable influence and decisive action for this reaction.
Embodiment 43-56
Except potassium tert.-butoxide is wherein replaced with respectively the following alkali cpd, implemented embodiment 43-56 respectively in the mode identical with embodiment 1-14, the yield of the alkali cpd that uses, embodiment corresponding relation and corresponding product is as shown in the table.
*: DABCO is 1,4-diazabicylo [2.2.2] octane
As seen from the above table, when adopting other alkali cpd, reaction almost can not be carried out, even use and potassium tert.-butoxide react and also almost can not carry out very similarly when trimethyl carbinol lithium, sodium tert-butoxide, and this has proved that alkali cpd has decisive influence to this reaction.
In sum, can clearly be found out by above-mentioned all embodiment, when adopting method of the present invention, especially use Cu (acac)
2As catalyzer, potassium tert.-butoxide during as alkali cpd, can realize the reaction of nitrobenzene compound, phenylo boric acid compound smoothly, obtain corresponding diaryl aniline compound, thereby provide brand-new synthetic route for the efficient quick of this compounds is synthetic, good prospects for application and industrial value have been arranged.
The purposes that should be appreciated that these embodiment only is used for explanation the present invention but not is intended to limit protection scope of the present invention.In addition; also should understand; after having read technology contents of the present invention, those skilled in the art can make various changes, modification and/or modification to the present invention, and these all equivalent form of values fall within the protection domain that the application's appended claims limits equally.
Claims (10)
1. the synthetic method of diaryl aniline compound shown in the formula (I);
Described method comprises: is catalyzer with the acetylacetone copper, in the presence of alkali and in organic solvent, formula (II) nitrobenzene compound and formula (III) phenylo boric acid compound reacted, thus the diaryl aniline compound of the formula of making (I);
R wherein
1Be selected from H, halogen, aldehyde radical, C independently of one another
1-C
6Alkyl, C
1-C
6Alkoxyl group, halo C
1-C
6Alkyl or halo C
1-C
6Alkoxyl group;
R
2Be selected from H, halogen, C independently of one another
1-C
6Alkyl, C
1-C
6Alkoxyl group, halo C
1-C
6Alkyl or halo C
1-C
6Alkoxyl group.
2. synthetic method as claimed in claim 1 is characterized in that: described alkali be selected from alkali metal hydroxide, the alkali metal alcoholates any one or multiple.
3. synthetic method as claimed in claim 1 or 2, it is characterized in that: described alkali be described alkali be in LiOH, NaOH, KOH, CsOH, sodium methylate, potassium methylate, sodium ethylate, potassium ethylate, sodium tert-butoxide or the potassium tert.-butoxide any one or multiple arbitrarily, most preferably be potassium tert.-butoxide.
4. as each described synthetic method of claim 1-3, it is characterized in that: described organic solvent is selected from toluene, dimethylbenzene, chlorobenzene, dimethyl sulfoxide (DMSO) (DMSO), tetrahydrofuran (THF) (THF), 1, any or multiple in the 4-dioxane most preferably is 1,4-dioxane.
5. as each described synthetic method of claim 1-4, it is characterized in that: formula (II) is 1:2-4 with (III) mol ratio of compound.
6. as each described synthetic method of claim 1-5, it is characterized in that: the mol ratio of formula (II) compound and acetylacetone copper is 1:0.05-0.2.
7. as each described synthetic method of claim 1-6, it is characterized in that: the mol ratio of formula (II) compound and alkali is 1:2-6.
8. as each described synthetic method of claim 1-7, it is characterized in that: temperature of reaction is 80-140 ℃; Reaction times is 10-14 hour.
9. as each described synthetic method of claim 1-8, it is characterized in that: be reflected under the protection of inert gas and carry out.
10. as each described synthetic method of claim 1-9, it is characterized in that:
Formula (II) is 1:3 with the mol ratio of formula (III) compound, and/or
The mol ratio of formula (II) compound and acetylacetone copper is 1:0.1, and/or
The mol ratio of formula (II) compound and alkali is 1:4, and/or
Organic solvent is 1,4-dioxane, and/or
Temperature of reaction is 110 ℃, and/or
Reaction times is 12 hours, and/or
Be reflected under the nitrogen protection and carry out.
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| CN114471731A (en) * | 2022-03-02 | 2022-05-13 | 淮阴师范学院 | Preparation method, product and application of Cu (I) catalyst |
| WO2023024532A1 (en) * | 2021-08-24 | 2023-03-02 | 江苏科技大学 | One-step method for preparing c-n coupling product using nitroaromatic hydrocarbon and alkyl or phenylboronic acid |
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| CN104098476A (en) * | 2014-08-04 | 2014-10-15 | 庄伟萍 | Composite method for amine compound serving as medicine structuring unit |
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| CN109232289A (en) * | 2018-09-10 | 2019-01-18 | 绍兴文理学院 | A kind of preparation method of N, N- diaryl amide derivatives |
| CN109232289B (en) * | 2018-09-10 | 2021-04-13 | 绍兴文理学院 | Preparation method of N, N-diaryl amide derivative |
| CN110668960A (en) * | 2019-10-22 | 2020-01-10 | 西北民族大学 | Preparation method of alpha-aryl alpha-aminoketone compound |
| WO2023024532A1 (en) * | 2021-08-24 | 2023-03-02 | 江苏科技大学 | One-step method for preparing c-n coupling product using nitroaromatic hydrocarbon and alkyl or phenylboronic acid |
| CN114471731A (en) * | 2022-03-02 | 2022-05-13 | 淮阴师范学院 | Preparation method, product and application of Cu (I) catalyst |
| CN114471731B (en) * | 2022-03-02 | 2022-10-04 | 淮阴师范学院 | Preparation method, product and application of Cu (I) catalyst |
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