CN101993318A - Preparation method of aromatic halogenated compound - Google Patents
Preparation method of aromatic halogenated compound Download PDFInfo
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- CN101993318A CN101993318A CN2009100913358A CN200910091335A CN101993318A CN 101993318 A CN101993318 A CN 101993318A CN 2009100913358 A CN2009100913358 A CN 2009100913358A CN 200910091335 A CN200910091335 A CN 200910091335A CN 101993318 A CN101993318 A CN 101993318A
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Abstract
The invention discloses a preparation method of an aromatic halogenated compound. Arene Ar-H and N-halogenated succimide are reacted in an organic solvent under the catalysis of auric chloride to obtain an aromatic halogenated compound Ar-X, wherein Ar represents substituted or unsubstituted non-heterocycle aryl and X represents chlorine, bromine or iodine. The reaction in the method does not need strict water-free and oxygen-free condition and occurs successfully in air. The invention has the advantages of good tolerance and universality to functional groups, little use amount of the catalyst and lower reaction cost, is simple and convenient for operation, and can be widely used for preparing the aromatic halogenated compound.
Description
Technical field
The invention belongs to the organic synthesis field, relate in particular to a kind of preparation method of fragrant halogenated compound.
Background technology
The fragrance halogenated compound is the very important industrial chemicals of a class, is widely used in the middle of scientific research and the industrial production.In scientific research, fragrant halogenated compound is mainly used in organic synthesis, and they can be used as molecular building block, participates in miscellaneous organic chemical reactions and makes up comparatively complicated target compound; In the middle of industrial production, fragrant halogenated compound is mainly used in industries such as dyestuff, material, medicine and agricultural chemicals.All the time, people constantly improve the synthetic method of fragrant halogenated compound and are perfect.In the present known synthetic method, major part all is to use aromatic hydrocarbon under lewis acidic catalysis and the (chlorine of halogen source, liquid bromine or N-halogenated succinimide imide etc.) reaction obtains fragrant halogenated compound, the shortcoming of these methods is to use a large amount of lewis acid catalysts, sometimes need equivalent catalyzer even more for comparing the inert substrate, and reaction conditions relatively more violent (chlorine, liquid bromine, the strong lewis acid environment), not easy to operate.
Summary of the invention
The purpose of this invention is to provide a kind of directly reaction and the efficient easily preparation method of the fragrant halogenated compound of row in air, this method has substrate adaptability more widely, can synthesize numerous fragrant halogenated compounds that have different substituents by this method.
The technical scheme of the inventive method is as follows:
A kind of preparation method of fragrant halogenated compound, aromatic hydrocarbon Ar-H and N-halogenated succinimide imide (shown in II) react in organic solvent under the catalysis of gold perchloride, obtain fragrant halogenated compound Ar-X, and its reaction formula is as follows:
Wherein: the aromatic base in the described aromatic hydrocarbon (Ar-) is non-heterocyclic aromatic base, such as phenyl and naphthyl etc.; Described aromatic base can be to replace or unsubstituted aromatic base; X represents chlorine, bromine or iodine.
Above-mentioned reaction pair functional group has good tolerance, can have one or more substituting groups on the aromatic base, substituent position is not particularly limited, ortho position, a position, contraposition all can, newly-generated carbon-halogen bond meets the rule on orientation of aromatic ring cationoid reaction.Common substituting group is alkyl, alkoxyl group, amide group, ester group and halogen etc. for example.When having a plurality of substituting group, these a plurality of substituting groups can be identical or different, and two adjacent substituting groups can separate or Cheng Huan.
Typically, when described aromatic base was phenyl, the reaction formula of the inventive method can be expressed as follows:
When described aromatic base was naphthyl, the reaction formula of the inventive method can be expressed as follows:
Wherein: R represents the substituted radical on the aromatic base, can be alkyl, alkoxyl group, amide group, ester group or halogen etc.; In formula Ia and IIIa, n=0,1,2,3,4 or 5; In formula Ib and IIIb, n=0,1,2,3,4,5,6 or 7; When n 〉=2, these a plurality of R groups are identical or different, two adjacent separate or Cheng Huan of R group; In formula III b, X and R group can be positioned on the identical or different phenyl ring.
Abovementioned alkyl preferably refers to have the alkyl of 1～10 carbon atom, for example methyl, ethyl, propyl group, sec.-propyl, butyl, isobutyl-, the tertiary butyl, sec-butyl, amyl group, neo-pentyl etc.; The alkyl that more preferably has 1～4 carbon atom, special preferable methyl, ethyl and propyl group.
Above-mentioned alkoxyl group preferably refers to have the alkoxyl group of 1～10 carbon atom, for example methoxyl group, oxyethyl group, propoxy-, isopropoxy, butoxy, isobutoxy, tert.-butoxy, sec-butoxy etc.; The alkoxyl group that more preferably has 1～4 carbon atom, preferred especially methoxyl group, oxyethyl group and isopropoxy.
Above-mentioned amide group is kharophen, propionamido and butyrylamino etc. for example.
Above-mentioned ester group is formic acid ester group, acetate groups, propionic acid ester group and butyric acid ester group etc. for example.
Above-mentioned halogen is meant fluorine, chlorine, bromine or iodine atom, preferred fluorine and chlorine.
The employed catalyzer gold perchloride of the inventive method useful commercial reagent need not special processing.Its catalytic amount is preferably in based on the normal scope of the 0.01-1% of described aromatic hydrocarbon.
The employed organic solvent of the inventive method is a kind of in following collection preferably: methylene dichloride, 1,2-ethylene dichloride, hexane.These organic solvents also get final product with commercialization reagent, need not special processing.Its consumption is preferably 1-2 milliliter/mmol aromatic hydrocarbon.
By top reaction formula as can be known, two kinds of preferred molar ratios of reactant of the inventive method are 1: 1.
The temperature of reaction of above-mentioned reaction is slightly different according to different raw materials with the reaction times, detects to disappear with raw material to be as the criterion, and generally in 0 ℃-80 ℃ scope, the reaction times is generally at 1-36 hour for temperature of reaction.Heat-processed can adopt oil bath (for example silicone oil, paraffin wet goods) or other type of heating.
The present invention preferably carries out aftertreatment to reaction product after reaction is finished, comprise concentrating and purifying.
Described concentration process can adopt methods such as air distillation, underpressure distillation, for example uses the Rotary Evaporators vacuum concentration.
Described purge process is that the mode by column chromatography, underpressure distillation or recrystallization obtains purified product.
Compare with prior art, the present invention has following advantage:
1, the related reaction of the inventive method does not need strict anhydrous and oxygen-free condition, can take place smoothly in air, and is easy to operate simple;
2, the related reaction pair functional group of the inventive method has good tolerance, substituting group can be alkyl, alkoxyl group, ester group, amide group and halogen atom (F, Cl, Br, I) etc., and newly-generated carbon-halogen bond meets the rule on orientation of aromatic ring cationoid reaction, can predict.
3, the related reaction of the inventive method uses gold perchloride as catalyzer, for most of substrate, catalyst consumption can be reduced to 1% or below, react very efficient.Because catalyst levels is very little, so reaction cost is lower.
Embodiment
Further describe the present invention below in conjunction with embodiment, but the scope that does not limit the present invention in any way.
Embodiment 1
Synthesizing of para-bromoanisole
In the long pipe type reaction flask of 25mL, add 534mg (being 3mmol) N-bromo-succinimide, add 6mL1,2-ethylene dichloride solvent, and then take by weighing 324mg (being 3mmol) methyl-phenoxide, add gold perchloride 0.1mg (the 1mg gold perchloride is dissolved in 1mL 1, and the 2-ethylene dichloride takes out the 0.1mL injection system with microsyringe) at last, 80 ℃ of following reacting by heating, treat GC-MS monitoring reaction finish (about 20 hours).The reaction back concentrates, and does the eluent column chromatography purification with sherwood oil and can obtain para-bromoanisole, and its structure is shown below:
This compound is a colourless liquid, and productive rate is 96%, and its nuclear magnetic data is as follows:
1H?NMR(300MHz，CDCl
3)δ7.37(d，2H，J＝8.8Hz)，6.78(d，2H，J＝8.8Hz)，3.78(s，3H)；
13C?NMR(50MHz，CDCl
3)δ158.6，132.1，115.6，112.7，55.3；
Embodiment 2
Synthesizing of 2-methoxyl group-5-methyl-bromobenzoate
In the long pipe type reaction flask of 25mL, add 534mg (3mmol) N-bromo-succinimide, gold perchloride 1mg (0.003mmol), add 6mL 1,2-ethylene dichloride solvent, take by weighing 498mg (3mmol) O-Anisic Acid methyl esters at last again, 80 ℃ of down reactions, treat GC-MS monitoring reaction finish (about 23 hours).Reaction back concentrates, and with sherwood oil: the ethyl acetate volume ratio is 20: 1 an eluent column chromatography purification, can obtain 2-methoxyl group-5-methyl-bromobenzoate, and its structure is shown below:
This compound is a colourless liquid, productive rate 96%, and its nuclear magnetic data is as follows:
1H?NMR(200MHz，CDCl
3)δ7.90(d，1H，J＝2.6Hz)，7.55(dd，1H，J
1＝2.6Hz，J
2＝8.9Hz)，6.87(d，1H，J＝8.9Hz)，3.89(s，6H)；
13C?NMR(50MHz，CDCl
3)δ165.1，158.1，135.9，134.1，121.6，113.8，112.1，56.1，52.1.
Embodiment 3
4-bromo-1,2-methylenedioxybenzenes synthetic
In the long pipe type reaction flask of 25mL, add 356mg (2mmol) N-bromo-succinimide, gold perchloride 3mg (0.01mmol), add 4mL 1,2-ethylene dichloride solvent, take by weighing 244mg (2mmol) 1 at last again, the 2-methylenedioxybenzenes, GC-MS monitoring reaction finish (about 4 hours) is treated in reaction at room temperature.Reaction back concentrates, with the sherwood oil for the eluent column chromatography purification can obtain 4-bromo-1, the 2-methylenedioxybenzenes, its structure is shown below:
This compound is a colourless liquid, productive rate 92%, and its nuclear magnetic data is as follows:
1H?NMR(200MHz，CDCl
3)δ6.98～6.92(m，2H)，6.69(d，1H，J＝8.7Hz)，5.97(s，2H)；
13CNMR(50MHz，CDCl
3)δ146.9，124.3，113.0，112.2，110.3，109.5，101.5.
Embodiment 4
1-chloro-2,4-dimethoxy benzene synthetic
In the long pipe type reaction flask of 25mL, add 134mg (1mmol) N-chlorosuccinimide, gold perchloride 3mg (0.01mmol), add 2mL 1,2-ethylene dichloride solvent, take by weighing 138mg (1mmol) 1 at last again, the 3-dimethoxy benzene, GC-MS monitoring reaction finish (about 24 hours) is treated in reaction at room temperature.Reaction back concentrates, with the sherwood oil for the eluent column chromatography purification can obtain 1-chloro-2, the 4-dimethoxy benzene, its structure is shown below:
This compound is a colourless liquid, productive rate 96%, and its nuclear magnetic data is as follows:
1H?NMR(200MHz，CDCl
3)δ7.24(d，1H，J＝8.6Hz)，6.50(d，1H，J＝2.7Hz)，6.43(dd，1H，J
1＝2.7Hz，J
2＝8.6Hz)，3.87(s，3H)，3.79(s，3H)；
13C?NMR(50MHz，CDCl
3)δ159.4，155.6，130.0，114.1，105.1，100.0，56.0，55.5.
Embodiment 5
Synthesizing of 4-iodo-3-methoxyphenylboronic acid pinacol ester
In the long pipe type reaction flask of 25mL, add 225mg (1mmol) N-iodo succimide, gold perchloride 3mg (0.01mmol), add 2mL 1,2-ethylene dichloride solvent, take by weighing 234mg (1mmol) 3-methoxyphenylboronic acid pinacol ester at last again, GC-MS monitoring reaction finish (about 24 hours) is treated in reaction at room temperature.The reaction back concentrates, and for the eluent column chromatography purification can obtain 4-iodo-3-methoxyphenylboronic acid pinacol ester, its structure is shown below with the sherwood oil:
This compound is a weak yellow liquid, productive rate 92%, and its nuclear magnetic data is as follows:
1H?NMR(200MHz，CDCl
3)δ7.68(d，1H，J＝8.7Hz)，7.07(d，1H，J＝3.2Hz)，6.66(dd，1H，J
1＝3.2Hz，J
2＝8.7Hz)，3.78(s，3H)，1.38(s，12H)；
13C?NMR(50MHz，CDCl
3)δ158.8，140.1，121.4，118.2，110.2，88.8，84.4，55.2，24.7.
Embodiment 6
Synthesizing of 1-bromonaphthalene
Add 178mg (1mmol) N-iodo succimide in the long pipe type reaction flask of 25mL, gold perchloride 3mg (0.01mmol) adds 2mL 1,2-ethylene dichloride solvent, take by weighing 128mg (1mmol) naphthalene at last again, GC-MS monitoring reaction finish (about 8 hours) is treated in reaction at room temperature.The reaction back concentrates, and for the eluent column chromatography purification can obtain the 1-bromonaphthalene, its structure is shown below with the sherwood oil:
This compound is a colourless liquid, productive rate 95%, and its nuclear magnetic data is as follows:
1H?NMR(200MHz，CDCl
3)δ8.23(d，1H，J＝8.1Hz)，7.86～7.75(m，3H)，7.62～7.44(m，2H)，7.33～7.22(m，1H)；
13C?NMR(50MHz，CDCl
3)δ134.6，131.9，129.8，128.2，127.8，127.2，127.0，126.6，126.1，122.8.
Claims (10)
1. the preparation method of a fragrant halogenated compound is a catalyzer with the gold perchloride, and aromatic hydrocarbon Ar-H and N-halogenated succinimide imide react in organic solvent, obtain fragrant halogenated compound Ar-X, and its reaction formula is as follows:
Wherein: the Ar representative replaces or unsubstituted non-heterocyclic aromatic base; X represents chlorine, bromine or iodine.
2. preparation method as claimed in claim 1 is characterized in that, described non-heterocyclic aromatic base is a phenyl or naphthyl.
3. preparation method as claimed in claim 1, it is characterized in that, Ar is for having one or more identical or different substituent aromatic bases, and described substituting group is selected from alkyl, alkoxyl group, amide group, ester group and halogen, two adjacent separate or Cheng Huan of substituting group.
4. preparation method as claimed in claim 1 is characterized in that, the catalytic amount of gold perchloride is in based on the normal scope of the 0.01-1% of described aromatic hydrocarbon.
5. preparation method as claimed in claim 1 is characterized in that, described organic solvent is selected from a kind of in the following solvent: methylene dichloride, 1,2-ethylene dichloride and hexane.
6. preparation method as claimed in claim 1 is characterized in that, the consumption of described organic solvent uses 1-2 milliliter organic solvent by every mmole aromatic hydrocarbon.
7. preparation method as claimed in claim 1 is characterized in that, temperature of reaction is 0 ℃-80 ℃.
8. preparation method as claimed in claim 1 is characterized in that, reaction times 1-36 hour.
9. preparation method as claimed in claim 1 is characterized in that, after reaction is finished reaction product is concentrated and purifying.
10. preparation method as claimed in claim 9 is characterized in that, by normal pressure or underpressure distillation reaction product is concentrated, and enriched product is through carrying out the product after underpressure distillation or recrystallization obtain purifying again behind the column chromatography.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102241699A (en) * | 2010-05-14 | 2011-11-16 | 北京大学 | Preparation method of halogenated aryl borate compounds |
| CN106083539A (en) * | 2016-06-15 | 2016-11-09 | 郑州泰基鸿诺医药股份有限公司 | A kind of single fluorine methoxyl group or the synthetic method of single fluorine deuterated methoxyl group compounds |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1785952A (en) * | 2004-12-07 | 2006-06-14 | 潘国平 | Method of preparing 3'-chlorophenyl acetone |
| CN102241699A (en) * | 2010-05-14 | 2011-11-16 | 北京大学 | Preparation method of halogenated aryl borate compounds |
-
2009
- 2009-08-18 CN CN200910091335.8A patent/CN101993318B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1785952A (en) * | 2004-12-07 | 2006-06-14 | 潘国平 | Method of preparing 3'-chlorophenyl acetone |
| CN102241699A (en) * | 2010-05-14 | 2011-11-16 | 北京大学 | Preparation method of halogenated aryl borate compounds |
Non-Patent Citations (6)
| Title |
|---|
| DI QIU ET AL: "Gold(III)-Catalyzed Halogenation of Aromatic Boronates with N-Halosuccinimides", 《ORGANIC LETTERS》 * |
| DIPANNITA KALYANI ET AL: "A Simple Catalytic Method for the Regioselective Halogenation of Arenes", 《ORGANIC LETTERS》 * |
| FANYANG MO ET AL: "Gold-Catalyzed Halogenation of Aromatics by N-Halosuccinimides", 《ANGEWANDTE CHEMIE INTERNATIONAL EDITION》 * |
| M. S. KHARASCH ET AL: "The Chemistry of Organic Gold Compounds. III. Direct Introduction of Gold into the Aromatic Nucleus (Preliminary Communication)", 《JOURNAL OF THE AMERICAN CHEMICAL SOCIETY》 * |
| SANJAY SINGH ET AL: "Effect of halogen addition to monolayer protected gold nanoparticles", 《JOURNAL OF MATERIALS CHEMISTRY》 * |
| 马红燕等: "等物质的量规则和当量定律的关系探讨", 《延安大学学报（自然科学版）》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102241699A (en) * | 2010-05-14 | 2011-11-16 | 北京大学 | Preparation method of halogenated aryl borate compounds |
| CN102241699B (en) * | 2010-05-14 | 2014-02-19 | 北京大学 | Preparation method of halogenated aryl borate compounds |
| CN106083539A (en) * | 2016-06-15 | 2016-11-09 | 郑州泰基鸿诺医药股份有限公司 | A kind of single fluorine methoxyl group or the synthetic method of single fluorine deuterated methoxyl group compounds |
| CN106083539B (en) * | 2016-06-15 | 2018-10-23 | 郑州泰基鸿诺医药股份有限公司 | A kind of synthetic method of list fluorine methoxyl group or the deuterated methoxy base class compound of single fluorine |
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