CN106748809B - A method of adjacent halogen arylamine is prepared based on C-H activation arylamine class - Google Patents
A method of adjacent halogen arylamine is prepared based on C-H activation arylamine class Download PDFInfo
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- CN106748809B CN106748809B CN201611085542.9A CN201611085542A CN106748809B CN 106748809 B CN106748809 B CN 106748809B CN 201611085542 A CN201611085542 A CN 201611085542A CN 106748809 B CN106748809 B CN 106748809B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/68—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton
- C07C209/74—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton by halogenation, hydrohalogenation, dehalogenation, or dehydrohalogenation
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/82—Purification; Separation; Stabilisation; Use of additives
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Abstract
The invention belongs to technical field of organic chemistry, and in particular to a kind of method that C-H activation arylamine class prepares halogenated compound.The method of the present invention are as follows: with Salicylaldoxime be catalysts, hydrogen peroxide is oxidant, and amino benzenes compounds and potassium bromide or potassium iodide are added to the water, and is reacted at room temperature two hours, it is extracted with ethyl acetate, is concentrated under reduced pressure to give corresponding arylamine halogenated compound crude product.Corresponding sterling is obtained by column chromatographic isolation and purification.The present invention has the characteristics that easy to operate, reaction condition is mild, the reaction time is short and environmentally protective.
Description
Technical field
The invention belongs to technical field of organic chemistry, and in particular to a kind of fragrant Ammonia of copper catalysis prepares the side of halogenated compound
Method.
Background technique
Adjacent halogen arylamine is the very extensive fine chemicals intermediate of a kind of purposes.In terms of medicine, adjacent halobenzene amine conduct
Medicine intermediate can prepare hundreds of drug, such as quinoline thiadiazine dioxide can be used as antibacterial agent for treating liver
It is scorching.In terms of dyestuff, it can be used for preparing traditional azo dyes and sulfur dye, four azo dyes of preparation are used for cotton
The dyeing of flower, wool, silk etc..In addition, adjacent halobenzene amine can also be used in the ligand for preparing complex compound, for antioxidant, fire retardant,
Developer and petroleum additive.Traditional halogenation generally requires stringent condition, and universal yield is lower, these are deposited
Difficulty greatly reduce for halogenation progress of research, and increase its research cost and difficulty.Therefore, it finds
Simple, the efficient halogenation condition of one kind is necessary.
Summary of the invention
The object of the present invention is to provide a kind of new methods of halogen on fragrant Ammonia ortho position, and reaction condition is mild, environmentally friendly, and
And only need a step can high yield halogen analog derivative is made, provide that a kind of simple, effective, catalyst is cheap for halogen compounds
It is easy to get and environmental-friendly preparation method.
The technical solution adopted by the present invention is that:
A kind of preparation method of adjacent halogen arylamine as shown in formula (i) or formula (ii):
Formula (III) or formula (IV) compound represented is soluble in water, catalyst, halogenating agent, oxidant, reaction is added
It is post-processed after completely up to neighbour's halogen arylamine shown in formula (I) or formula (II)；The halide reagent, oxidant, catalyst and formula
(III) or the ratio between the amount of substance of compound shown in formula (IV) is 1~5:0.5~5:0.1~0.5:1；The catalyst is acetic acid
Copper, cupric iodide or cuprous iodide；The sulfonated reagent is potassium bromide or potassium iodide；The oxidant is hydrogen peroxide, tert-butyl
Hydrogen peroxide or manganese dioxide；
In formula (I) or formula (III), R is that H or H is respectively monosubstituted or polysubstituted by methyl, ethyl or n-propyl, and n is to replace
Base number, n=1~2；In formula (I) or formula (II), X1For bromine or iodine, X2For bromine or iodine.
Further, R of the present invention is that H or H is monosubstituted by methyl, ethyl or n-propyl.
Further, R of the present invention is that H or H is polysubstituted by methyl.
The reaction equation of formula (III) preparation of compounds of formula (I) compound of the present invention is as follows:
The reaction equation of formula (IV) preparation of compounds of formula (II) compound of the present invention is as follows:
Catalyst of the present invention is preferably copper acetate.
Further, halogenating agent of the present invention is preferably potassium bromide or potassium iodide.
Further, oxidant of the present invention is preferably hydrogen peroxide.
Further, compound shown in halide reagent of the present invention, oxidant, catalyst and formula (III) or formula (IV)
The ratio between amount of substance is preferably 2:2:0.25:1.
Post-processing of the present invention are as follows: saturation NaCl aqueous solution is added after fully reacting, in reaction solution, is extracted with ethyl acetate
It takes, takes rotation under organic layer dry by anhydrous magnesium sulfate, filtering, room temperature that solvent is evaporated off to get crude product；Crude product is subjected to silica gel
Column chromatography, using the volume ratio of ethyl acetate and petroleum ether for 1:2~7 solution as mobile phase, TLC tracking collect Rf value be 0.3-
0.5 eluent, the eluent collected removes solvent through vacuum distillation, dry, obtains neighbour shown in formula (I) or formula (II)
Halogen arylamine.
Compared with the conventional method, its advantages are embodied in the present invention:
(1) the present invention provides the preparation method that a kind of C-H activation arylamine class prepares adjacent halogen arylamine, operating process is simple,
Raw material sources have all been commercialized and have been easy to get.
(2) traditional method to arylamine class halogenation is reacted in organic solvent, and the reaction time is long, obtained product
It is not single；It is compared with the traditional method, the method is more efficient, quick, environmentally friendly, obtains single product.
Specific embodiment
The present invention is described further combined with specific embodiments below, but protection scope of the present invention is not limited in
This.
Embodiment 1
Prepare 2- bromaniline
0.5mmol aniline (1a) is added in the water of 4mL, 0.125mmol copper acetate, 1.0mmol bromination are added thereto
Potassium, 1.0mmol hydrogen peroxide react 2 hours at room temperature, saturation NaCl aqueous solution are added after reaction, in reaction solution, uses second
Acetoacetic ester extraction takes organic layer dry by anhydrous magnesium sulfate, filtering, 60 DEG C of evaporated under reduced pressure to get the formula (2a) shownization
Close object crude product.By crude compound shown in formula (2a) into silica gel column chromatography, the volume ratio with ethyl acetate and petroleum ether is 1:5's
Solution is mobile phase, and the eluent that Rf value is 0.3-0.5 is collected in TLC tracking, the eluent collected through solvent is removed under reduced pressure,
It is dry, obtain formula (2a) compound represented sterling 43mg, yield 50%.
1H NMR(500MHz,CDCl3) δ 6.95 (dd, J=7.9,1.2Hz, 1H), 6.88 (td, J=7.7,1.3Hz,
1H), 6.61 (td, J=7.7,1.3Hz, 1H), 6.50 (dd, J=7.9,1.3Hz, 1H), 3.81 (s, 2H)13C NMR
(126MHz,CDCl3)δ147.2,132.4,128.5,126.2,115.4,107.5.
Embodiment 2
Prepare 2- Iodoaniline
0.5mmol aniline (1b) is added in the water of 4mL, 0.125mmol copper acetate, 1.0mmol iodate are added thereto
Potassium, 1.0mmol hydrogen peroxide react 2 hours at room temperature, saturation NaCl aqueous solution are added after reaction, in reaction solution, uses second
Acetoacetic ester extraction takes organic layer dry by anhydrous magnesium sulfate, filtering, 60 DEG C of evaporated under reduced pressure to get the formula (2b) shownization
Close object crude product.By crude compound shown in formula (2b) into silica gel column chromatography, the volume ratio with ethyl acetate and petroleum ether is 1:5's
Solution is mobile phase, and the eluent that Rf value is 0.3-0.5 is collected in TLC tracking, the eluent collected through solvent is removed under reduced pressure,
It is dry, obtain formula (2b) compound represented sterling 40mg, yield 37%.
1H NMR(500MHz,CDCl3) δ 7.65 (dd, J=7.8,1.2Hz, 1H), 6.83 (td, J=7.6,1.3Hz,
1H), 6.79 (td, J=7.7,1.3Hz, 1H), 6.31 (dd, J=7.8,1.3Hz, 1H), 4.01 (s, 2H)13C NMR
(126MHz,CDCl3)δ148.3,138.4, 128.4,120.3,114.4,83.9.
Embodiment 3
Prepare the bromo- 6- methylaniline of 2-
0.5mmol ortho-aminotoluene (1c) is added in the water of 4mL, 0.125mmol copper acetate, 1.0mmol are added thereto
Potassium bromide, 1.0mmol hydrogen peroxide react 2 hours at room temperature, saturation NaCl aqueous solution are added after reaction, in reaction solution,
It is extracted with ethyl acetate, takes organic layer dry by anhydrous magnesium sulfate, filtering, 60 DEG C of evaporated under reduced pressure to get the formula (2c) institute
Show crude compound.By crude compound shown in formula (2c) into silica gel column chromatography, the volume ratio with ethyl acetate and petroleum ether is
The solution of 1:4 is mobile phase, and the eluent that Rf value is 0.3-0.5 is collected in TLC tracking, and the eluent collected is through being removed under reduced pressure
Solvent, it is dry, obtain formula (2c) compound represented sterling 36mg, yield 39%.
1H NMR(500MHz,CDCl3) δ 7.45 (d, J=7.8Hz, 1H), 6.98 (d, J=7.4Hz, 1H), 6.65 (t, J
=7.7Hz, 1H), 4.32 (dt, J=113.0,56.6Hz, 2H), 2.16 (s, 3H)13C NMR(126MHz,CDCl3)δ
143.0,131.2,130.3,129.4,119.4,117.2,16.6.
Embodiment 4
Prepare the iodo- 6- methylaniline of 2-
0.5mmol ortho-aminotoluene (1d) is added in the water of 4mL, 0.125mmol copper acetate, 1.0mmol are added thereto
Potassium iodide, 1.0mmol hydrogen peroxide react 2 hours at room temperature, saturation NaCl aqueous solution are added after reaction, in reaction solution,
It is extracted with ethyl acetate, takes organic layer dry by anhydrous magnesium sulfate, filtering, 60 DEG C of evaporated under reduced pressure to get the formula (2d) institute
Show crude compound.By crude compound shown in formula (2d) into silica gel column chromatography, the volume ratio with ethyl acetate and petroleum ether is
The solution of 1:4 is mobile phase, and the eluent that Rf value is 0.3-0.5 is collected in TLC tracking, and the eluent collected is through being removed under reduced pressure
Solvent, it is dry, obtain formula (2d) compound represented sterling 48mg, yield 41%.
1H NMR(500MHz,CDCl3) δ 7.56 (d, J=7.6Hz, 1H), 6.89 (d, J=7.2Hz, 1H), 6.64 (t, J
=7.9Hz, 1H), 4.68 (dt, J=113.0,56.6Hz, 2H), 2.12 (s, 3H)13C NMR(126MHz,CDCl3)δ
156.3,135.4,130.6,130.2,120.2,83.8,16.4.
Embodiment 5
The bromo- 4,6- dimethylaniline of 2-
By 0.5mmol 2,4- dimethylaniline (1e) is added in the water of 4mL, and 0.125mmol copper acetate is added thereto,
1.0mmol potassium bromide, 1.0mmol hydrogen peroxide react 2 hours at room temperature, saturation NaCl are added after reaction, in reaction solution
Aqueous solution is extracted with ethyl acetate, and takes organic layer dry by anhydrous magnesium sulfate, filtering, 60 DEG C of evaporated under reduced pressure to get the formula
Crude compound shown in (2e).By crude compound shown in formula (2e) into silica gel column chromatography, with the body of ethyl acetate and petroleum ether
Product is mobile phase than the solution for being 1:6, and the eluent that Rf value is 0.3-0.5 is collected in TLC tracking, and the eluent collected is through subtracting
Pressure removes solvent, dry, obtains formula (2e) compound represented sterling 40mg, yield 40%.
1H NMR(500MHz,CDCl3)δ7.07(s,1H),6.70(s,1H),3.68(s,2H),2.36(s,3H),2.13
(s,3H).13C NMR(126MHz,CDCl3)δ140.0,131.6,131.1,130.7,130.5,117.1,20.9,16.9.
Embodiment 6
The iodo- 4,6- dimethylaniline of 2-
By 0.5mmol 2,4- dimethylaniline (1f) is added in the water of 4mL, and 0.125mmol copper acetate is added thereto,
1.0mmol potassium iodide, 1.0mmol hydrogen peroxide react 2 hours at room temperature, saturation NaCl are added after reaction, in reaction solution
Aqueous solution is extracted with ethyl acetate, and takes organic layer dry by anhydrous magnesium sulfate, filtering, 60 DEG C of evaporated under reduced pressure to get the formula
Crude compound shown in (2f).By crude compound shown in formula (2f) into silica gel column chromatography, with the body of ethyl acetate and petroleum ether
Product is mobile phase than the solution for being 1:7, and the eluent that Rf value is 0.3-0.5 is collected in TLC tracking, and the eluent collected is through subtracting
Pressure removes solvent, dry, obtains formula (2f) compound represented sterling 48mg, yield 39%.
1H NMR(500MHz,CDCl3)δ7.44(s,1H),6.75(s,1H),3.98(s,2H),2.36(s,3H),2.13
(s,3H).13C NMR(126MHz,CDCl3)δ153.3,137.7,130.6,130.5,129.9,83.7,20.7,16.7.
Embodiment 7
The bromo- 6- ethyl aniline of 2-
0.5mmol 2- ethyl aniline (1g) is added in the water of 4mL, 0.125mmol copper acetate is added thereto,
1.0mmol potassium bromide, 1.0mmol hydrogen peroxide react 2 hours at room temperature, saturation NaCl are added after reaction, in reaction solution
Aqueous solution is extracted with ethyl acetate, and takes organic layer dry by anhydrous magnesium sulfate, filtering, 60 DEG C of evaporated under reduced pressure to get the formula
Crude compound shown in 2g.By crude compound shown in formula 2g into silica gel column chromatography, with the volume ratio of ethyl acetate and petroleum ether
Solution for 1:6 is mobile phase, and the eluent that Rf value is 0.3-0.5 is collected in TLC tracking, and the eluent collected is removed through decompression
Solvent is removed, it is dry, obtain formula (2g) compound represented sterling 43mg, yield 43%.
1H NMR(500MHz,CDCl3) δ 7.41 (dd, J=7.8,1.2Hz, 1H), 6.89 (d, J=7.7Hz, 1H), 6.70
(t, J=7.7Hz, 1H), 3.80 (s, 2H), 2.58 (q, J=7.6Hz, 2H), 1.24 (t, J=7.5Hz, 3H)13C NMR
(126MHz,CDCl3)δ141.7,129.6,127.8,124.4,119.4,117.2,22.4,14.5.
Embodiment 8
The iodo- 6- ethyl aniline of 2-
0.5mmol 2- ethyl aniline (1h) is added in the water of 4mL, 0.125mmol copper acetate is added thereto,
1.0mmol potassium iodide, 1.0mmol hydrogen peroxide react 2 hours at room temperature, saturation NaCl are added after reaction, in reaction solution
Aqueous solution is extracted with ethyl acetate, and takes organic layer dry by anhydrous magnesium sulfate, filtering, 60 DEG C of evaporated under reduced pressure to get the formula
Crude compound shown in 2h.By crude compound shown in formula 2h into silica gel column chromatography, with the volume ratio of ethyl acetate and petroleum ether
Solution for 1:6 is mobile phase, and the eluent that Rf value is 0.3-0.5 is collected in TLC tracking, and the eluent collected is removed through decompression
Solvent is removed, it is dry, obtain formula 2h compound represented sterling 47mg, yield 38%.
1H NMR(500MHz,CDCl3) δ 7.54 (dd, J=7.8,1.2Hz, 1H), 6.91 (d, J=7.8Hz, 1H), 6.69
(t, J=7.7Hz, 1H), 3.80 (s, 2H), 2.57 (q, J=7.6Hz, 2H), 1.22 (t, J=7.5Hz, 3H)13C NMR
(126MHz,CDCl3)δ155.0,135.6,127.2,124.3,120.2,83.8,22.2,14.5.
Embodiment 9
The bromo- 6- propyl aniline of 2-
0.5mmol 2- propyl aniline (1i) is added in the water of 4mL, 0.125mmol copper acetate is added thereto,
1.0mmol potassium bromide, 1.0mmol hydrogen peroxide react 2 hours at room temperature, saturation NaCl are added after reaction, in reaction solution
Aqueous solution is extracted with ethyl acetate, and takes organic layer dry by anhydrous magnesium sulfate, filtering, 60 DEG C of evaporated under reduced pressure to get the formula
Crude compound shown in 2i.By crude compound shown in formula 2i into silica gel column chromatography, with the volume ratio of ethyl acetate and petroleum ether
Solution for 1:6 is mobile phase, and the eluent that Rf value is 0.3-0.5 is collected in TLC tracking, and the eluent collected is removed through decompression
Solvent is removed, it is dry, obtain formula 2i compound represented sterling 44mg, yield 41%.
1H NMR (500MHz, CDCl3) δ 7.43 (d, J=7.8Hz, 1H), 6.89 (d, J=7.3Hz, 1H), 6.70 (t, J
=7.7Hz, 1H), 3.87 (s, 2H), 2.46-2.40 (m, 2H), 1.64 (dd, J=15.1,7.5Hz, 2H), 0.95 (t, J=
7.3Hz,3H).13C NMR(126MHz,CDCl3)δ142.1,129.7,126.4,124.8,119.6,117.4,32.1,24.1,
13.7.
Embodiment 10
The iodo- 6- propyl aniline of 2-
0.5mmol 2- propyl aniline (1j) is added in the water of 4mL, 0.125mmol copper acetate is added thereto,
1.0mmol potassium iodide, 1.0mmol hydrogen peroxide react 2 hours at room temperature, saturation NaCl are added after reaction, in reaction solution
Aqueous solution is extracted with ethyl acetate, and takes organic layer dry by anhydrous magnesium sulfate, filtering, 60 DEG C of evaporated under reduced pressure to get the formula
Crude compound shown in 2j.By crude compound shown in formula 2j into silica gel column chromatography, with the volume ratio of ethyl acetate and petroleum ether
Solution for 1:6 is mobile phase, and the eluent that Rf value is 0.3-0.5 is collected in TLC tracking, and the eluent collected is removed through decompression
Solvent is removed, it is dry, obtain formula 2j compound represented sterling 59mg, yield 45%.
1H NMR (500MHz, CDCl3) δ 7.49 (d, J=7.7Hz, 1H), 6.93 (d, J=7.3Hz, 1H), 6.69 (t, J
=7.6Hz, 1H), 3.87 (s, 2H), 2.46-2.41 (m, 2H), 1.63 (dd, J=15.2,7.5Hz, 2H), 0.95 (t, J=
7.3Hz,3H).13C NMR(126MHz,CDCl3)δ155.4,135.7,125.8,124.7,120.4,84.0,31.9,24.1,
13.7.
Embodiment 11
The bromo- 1- Aminotetralin of 2-
0.5mmol 1- Aminotetralin (1k) is added in the water of 4mL, 0.125mmol copper acetate is added thereto,
1.0mmol potassium bromide, 1.0mmol hydrogen peroxide react 2 hours at room temperature, saturation NaCl are added after reaction, in reaction solution
Aqueous solution is extracted with ethyl acetate, and takes organic layer dry by anhydrous magnesium sulfate, filtering, 60 DEG C of evaporated under reduced pressure to get the formula
Crude compound shown in 2k.By crude compound shown in formula 2k into silica gel column chromatography, with the volume ratio of ethyl acetate and petroleum ether
Solution for 1:2 is mobile phase, and the eluent that Rf value is 0.3-0.5 is collected in TLC tracking, and the eluent collected is removed through decompression
Solvent is removed, it is dry, obtain formula 2k compound represented sterling 41mg, yield 36%.
1H NMR(500MHz,CDCl3) δ 6.95 (d, J=8.1Hz, 1H), 6.27 (d, J=8.1Hz, 1H), 3.73 (s,
2H), 2.70 (t, J=6.1Hz, 2H), 2.69 (t, J=6.5Hz, 2H), 1.87-1.82 (m, 2H), 1.75-1.71 (m, 2H)
.13C NMR(126MHz,CDCl3)δ141.9,137.2,129.4,125.9,120.1,114.3,29.5,23.4,22.7,
22.6.
Embodiment 12
The iodo- 1- Aminotetralin of 2-
0.5mmol 1- Aminotetralin (1l) is added in the water of 4mL, 0.125mmol copper acetate is added thereto,
1.0mmol potassium iodide, 1.0mmol hydrogen peroxide react 2 hours at room temperature, saturation NaCl are added after reaction, in reaction solution
Aqueous solution is extracted with ethyl acetate, and takes organic layer dry by anhydrous magnesium sulfate, filtering, 60 DEG C of evaporated under reduced pressure to get the formula
Crude compound shown in 2l.By crude compound shown in formula 2l into silica gel column chromatography, with the volume ratio of ethyl acetate and petroleum ether
Solution for 1:2 is mobile phase, and the eluent that Rf value is 0.3-0.5 is collected in TLC tracking, and the eluent collected is removed through decompression
Solvent is removed, it is dry, obtain formula 2l compound represented sterling 41mg, yield 30%.
1H NMR(500MHz,CDCl3) δ 7.06 (d, J=8.0Hz, 1H), 6.38 (d, J=8.1Hz, 1H), 3.73 (s,
2H), 2.70 (t, J=6.2Hz, 2H), 2.69 (t, J=6.5Hz, 2H), 1.88-1.83 (m, 2H), 1.75-1.71 (m, 2H)
.13C NMR(126MHz,CDCl3)δ155.2,137.1,135.4,125.3,119.5,80.9,29.5,23.2,22.8,22.7.
Embodiment 13
Prepare 2- bromaniline
0.5mmol aniline (1a) is added in the water of 4mL, 0.05mmol copper acetate, 0.5mmol bromination are added thereto
Potassium, 0.25mmol hydrogen peroxide react 2 hours at room temperature, saturation NaCl aqueous solution are added after reaction, in reaction solution, uses
Ethyl acetate extraction takes organic layer dry by anhydrous magnesium sulfate, filtering, 60 DEG C of evaporated under reduced pressure to get shown in the formula (2a)
Crude compound.By crude compound shown in formula (2a) into silica gel column chromatography, the volume ratio with ethyl acetate and petroleum ether is 1:5
Solution be mobile phase, the eluent that Rf value is 0.3-0.5 is collected in TLC tracking, and the eluent collected is molten through being removed under reduced pressure
Agent, it is dry, obtain formula (2a) compound represented sterling 26mg, yield 30%.
1H NMR(500MHz,CDCl3) δ 6.95 (dd, J=7.9,1.2Hz, 1H), 6.88 (td, J=7.7,1.3Hz,
1H), 6.61 (td, J=7.7,1.3Hz, 1H), 6.50 (dd, J=7.9,1.3Hz, 1H), 3.81 (s, 2H)13C NMR
(126MHz,CDCl3)δ147.2,132.4,128.5,126.2,115.4,107.5.
Embodiment 14
Prepare 2- bromaniline
0.5mmol aniline (1a) is added in the water of 4mL, 0.25mmol copper acetate, 2.5mmol bromination are added thereto
Potassium, 2.5mmol hydrogen peroxide react 2 hours at room temperature, saturation NaCl aqueous solution are added after reaction, in reaction solution, uses second
Acetoacetic ester extraction takes organic layer dry by anhydrous magnesium sulfate, filtering, 60 DEG C of evaporated under reduced pressure to get the formula (2a) shownization
Close object crude product.By crude compound shown in formula (2a) into silica gel column chromatography, the volume ratio with ethyl acetate and petroleum ether is 1:5's
Solution is mobile phase, and the eluent that Rf value is 0.3-0.5 is collected in TLC tracking, the eluent collected through solvent is removed under reduced pressure,
It is dry, obtain formula (2a) compound represented sterling 33mg, yield 39%.
1H NMR(500MHz,CDCl3) δ 6.95 (dd, J=7.9,1.2Hz, 1H), 6.88 (td, J=7.7,1.3Hz,
1H), 6.61 (td, J=7.7,1.3Hz, 1H), 6.50 (dd, J=7.9,1.3Hz, 1H), 3.81 (s, 2H)13C NMR
(126MHz,CDCl3)δ147.2,132.4,128.5,126.2,115.4,107.5.
Embodiment 15
Prepare 2- bromaniline
0.5mmol aniline (1a) is added in the water of 4mL, 0.125mmol cupric iodide, 1.0mmol bromination are added thereto
Potassium, 1.0mmol hydrogen peroxide react 2 hours at room temperature, saturation NaCl aqueous solution are added after reaction, in reaction solution, uses second
Acetoacetic ester extraction takes organic layer dry by anhydrous magnesium sulfate, filtering, 60 DEG C of evaporated under reduced pressure to get the formula (2a) shownization
Close object crude product.By crude compound shown in formula (2a) into silica gel column chromatography, the volume ratio with ethyl acetate and petroleum ether is 1:5's
Solution is mobile phase, and the eluent that Rf value is 0.3-0.5 is collected in TLC tracking, the eluent collected through solvent is removed under reduced pressure,
It is dry, obtain formula (2a) compound represented sterling 29mg, yield 34%.
1H NMR(500MHz,CDCl3) δ 6.95 (dd, J=7.9,1.2Hz, 1H), 6.88 (td, J=7.7,1.3Hz,
1H), 6.61 (td, J=7.7,1.3Hz, 1H), 6.50 (dd, J=7.9,1.3Hz, 1H), 3.81 (s, 2H)13C NMR
(126MHz,CDCl3)δ147.2,132.4,128.5,126.2,115.4,107.5.
Embodiment 16
Prepare 2- bromaniline
0.5mmol aniline (1a) is added in the water of 4mL, 0.125mmol cuprous iodide, 1.0mmol bromine are added thereto
Change potassium, 1.0mmol hydrogen peroxide reacts 2 hours at room temperature, saturation NaCl aqueous solution is added after reaction, in reaction solution, uses
Ethyl acetate extraction takes organic layer dry by anhydrous magnesium sulfate, filtering, 60 DEG C of evaporated under reduced pressure to get shown in the formula (2a)
Crude compound.By crude compound shown in formula (2a) into silica gel column chromatography, the volume ratio with ethyl acetate and petroleum ether is 1:5
Solution be mobile phase, the eluent that Rf value is 0.3-0.5 is collected in TLC tracking, and the eluent collected is molten through being removed under reduced pressure
Agent, it is dry, obtain formula (2a) compound represented sterling 25mg, yield 29%.
1H NMR(500MHz,CDCl3) δ 6.95 (dd, J=7.9,1.2Hz, 1H), 6.88 (td, J=7.7,1.3Hz,
1H), 6.61 (td, J=7.7,1.3Hz, 1H), 6.50 (dd, J=7.9,1.3Hz, 1H), 3.81 (s, 2H)13C NMR
(126MHz,CDCl3)δ147.2,132.4,128.5,126.2,115.4,107.5.
Embodiment 17
Prepare 2- bromaniline
0.5mmol aniline (1a) is added in the water of 4mL, 0.125mmol copper acetate, 1.0mmol bromination are added thereto
Potassium, 1.0mmol tert-butyl hydroperoxide react 2 hours at room temperature, it is water-soluble that saturation NaCl are added after reaction, in reaction solution
Liquid is extracted with ethyl acetate, and takes organic layer dry by anhydrous magnesium sulfate, filtering, 60 DEG C of evaporated under reduced pressure to get the formula (2a)
Shown crude compound.By crude compound shown in formula (2a) into silica gel column chromatography, with the volume ratio of ethyl acetate and petroleum ether
Solution for 1:5 is mobile phase, and the eluent that Rf value is 0.3-0.5 is collected in TLC tracking, and the eluent collected is removed through decompression
Solvent is removed, it is dry, obtain formula (2a) compound represented sterling 39mg, yield 46%.
1H NMR(500MHz,CDCl3) δ 6.95 (dd, J=7.9,1.2Hz, 1H), 6.88 (td, J=7.7,1.3Hz,
1H), 6.61 (td, J=7.7,1.3Hz, 1H), 6.50 (dd, J=7.9,1.3Hz, 1H), 3.81 (s, 2H)13C NMR
(126MHz,CDCl3)δ147.2,132.4,128.5,126.2,115.4,107.5.
Embodiment 18
Prepare 2- bromaniline
0.5mmol aniline (1a) is added in the water of 4mL, 0.125mmol copper acetate, 1.0mmol bromination are added thereto
Potassium, 1.0mmol manganese dioxide react 2 hours at room temperature, saturation NaCl aqueous solution are added after reaction, in reaction solution, uses second
Acetoacetic ester extraction takes organic layer dry by anhydrous magnesium sulfate, filtering, 60 DEG C of evaporated under reduced pressure to get the formula (2a) shownization
Close object crude product.By crude compound shown in formula (2a) into silica gel column chromatography, the volume ratio with ethyl acetate and petroleum ether is 1:5's
Solution is mobile phase, and the eluent that Rf value is 0.3-0.5 is collected in TLC tracking, the eluent collected through solvent is removed under reduced pressure,
It is dry, obtain formula (2a) compound represented sterling 28mg, yield 33%.
1H NMR(500MHz,CDCl3) δ 6.95 (dd, J=7.9,1.2Hz, 1H), 6.88 (td, J=7.7,1.3Hz,
1H), 6.61 (td, J=7.7,1.3Hz, 1H), 6.50 (dd, J=7.9,1.3Hz, 1H), 3.81 (s, 2H)13C NMR
(126MHz,CDCl3)δ147.2,132.4,128.5,126.2,115.4,107.5。
Claims (7)
1. a kind of preparation method of adjacent halogen arylamine as shown in formula (i) or formula (ii), it is characterised in that the method are as follows:
Formula (III) or formula (IV) compound represented is soluble in water, catalyst, halogenating agent, oxidant, fully reacting is added
By post-processing up to neighbour's halogen arylamine shown in formula (I) or formula (II)；The halide reagent, oxidant, catalyst and formula (III)
Or the ratio between amount of substance of compound shown in formula (IV) is 1~5:0.5~5:0.1~0.5:1；The catalyst be copper acetate,
Cupric iodide or cuprous iodide；The halogenating agent is potassium bromide or potassium iodide；The oxidant is hydrogen peroxide, t-butyl peroxy
Change hydrogen or manganese dioxide；
In formula (I) or formula (III), R is that H or H is respectively monosubstituted or polysubstituted by methyl, ethyl or n-propyl, and n is substituent group
Number, n=1~2；In formula (I) or formula (II), X1For bromine or iodine, X2For bromine or iodine.
2. preparation method as described in claim 1, it is characterised in that: the R is that H or H is taken by methyl, ethyl or n-propyl list
Generation.
3. preparation method as described in claim 1, it is characterised in that: the R is that H or H is polysubstituted by methyl.
4. preparation method as described in claim 1, it is characterised in that: the catalyst is copper acetate.
5. preparation method as described in claim 1, it is characterised in that: the oxidant is hydrogen peroxide.
6. preparation method as described in claim 1, it is characterised in that: the halide reagent, oxidant, catalyst and formula (III)
Or the ratio between amount of substance of compound shown in formula (IV) is 2:2:0.25:1.
7. the preparation method as described in one of claim 1~6, it is characterised in that the post-processing are as follows: after fully reacting, reaction
Saturation NaCl aqueous solution is added in liquid, is extracted with ethyl acetate, takes under organic layer dry by anhydrous magnesium sulfate, filtering, room temperature
Solvent is evaporated off to get crude product in rotation；Crude product is subjected to silica gel column chromatography, the volume ratio with ethyl acetate and petroleum ether is 1:2~7
Solution be mobile phase, TLC tracking collect Rf value be 0.3-0.5 eluent, the eluent collected through vacuum distillation remove
Solvent is removed, it is dry, obtain neighbour's halogen arylamine shown in formula (I) or formula (II).
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