CN110642669A - Preparation method of para-substituted bromobenzene - Google Patents
Preparation method of para-substituted bromobenzene Download PDFInfo
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- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
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Abstract
The application relates to a preparation method of para-substituted bromobenzene shown in formula 2, which is characterized by comprising the following steps: in an organic solvent, under the condition of alkali existence, carrying out a Huang Minlon reaction on a compound shown as a formula 1 and hydrazine for a preset time period to obtain the compoundThe para-substituted bromobenzene shown in the formula 2:wherein R is selected from one or more of alkyl, halogenated alkyl, fluorinated alkyl, alkenyl, alkynyl, substituent substitution of carbocyclyl, heterocyclic radical, aryl, aralkyl, heteroaryl, heteroaralkyl, alkoxy, halogenated alkoxy, fluorinated alkoxy, alkenyloxy, alkynyloxy, carbocyclic oxy, heterocyclic oxy, aryloxy, aralkoxy, heteroaryloxy, heteroaralkoxy and amino. The preparation method has the advantages of good positioning effect, high purity of the prepared product, simple and safe operation, environmental friendliness and low production cost, and is suitable for industrial production.
Description
Technical Field
The application belongs to the technical field of organic synthesis, and particularly relates to a preparation method of para-substituted bromobenzene.
Background
Para-substituted bromobenzene has wide application, wherein the alkyl bromobenzene is mainly used for liquid crystal, and the bromobenzene with aromatic ring or heterocyclic ring is mainly used for synthesizing OLED luminescent material and green chemical reagents such as arylboronic acid.
The existing synthesis methods of substituted bromobenzene include the following methods:
for simple para-substituted alkylbromobenzene, the conventional synthetic process route is as follows:
in the conventional synthetic route, p-substituted alkylbromobenzene is obtained by brominating alkylbenzene with brominating agent. However, the product of this method is easily mixed with ortho-and meta-isomers, and separation and purification are difficult.
In order to obtain high-quality para-substituted alkylbromobenzene, researchers adopt para-alkylaniline to carry out diazotization and then Sandmeyer reaction bromination so as to avoid generating isomer impurities which are difficult to separate, and the specific synthetic route is as follows:
however, in this synthetic route, the diazonium salt is unstable, easy to decompose, dangerous to operate and unsuitable for industrial production.
In recent years, the cross-coupling reaction of a transition metal catalyzed metal organic reagent and halogenated hydrocarbon is a leading technology for preparing para-substituted bromobenzene, and the synthetic route is as follows:
although the cross-coupling technology can eliminate the generation of ortho/meta isomer impurities, the existing cross-coupling technology of aryl metal organic reagent and alkyl halogenated hydrocarbon must prepare aryl metal organic reagent in advance, and the p-bromophenyl Grignard reagent is unstable at normal temperature, difficult to prepare and has no practical application value, and the cross-coupling technology disclosed by the existing literature is difficult to apply to the practical production of p-substituted bromobenzene.
The synthesis method of para-substituted bromobenzene is disclosed in U.S. Pat. No. 4, 5514696A, and the corresponding para-substituted bromobenzene is obtained by reaction of Wittig reagent and 4-bromobenzaldehyde and hydrogenation. In the hydrogenation process, bromine is easy to drop, the product yield is reduced, and the Wittig reagent used is high in price and is not beneficial to reducing the cost.
Chinese patent application CN106278811A discloses a synthetic method of p-bromo linear alkylbenzene, which adopts dibromobenzene and straight-chain 1-alkyl halide to obtain the p-bromo linear alkylbenzene under the action of a catalyst.
Therefore, the search for a preparation method of para-substituted bromobenzene which has good positioning effect, high purity of the prepared product, high reaction yield and low cost and is suitable for industrial production is a technical problem which needs to be solved urgently at present.
Disclosure of Invention
The application aims to overcome the defects that the preparation method of the para-substituted bromobenzene in the prior art is complex in operation, poor in safety, poor in positioning effect, easy to generate ortho-position and meta-position isomers, difficult in separation and purification, poor in purity of the prepared product, low in yield, high in production cost, not suitable for industrial production and the like, and the preparation method of the para-substituted bromobenzene is provided. The preparation method has the advantages of good positioning effect, high purity of the prepared product, simple and safe operation, environmental friendliness and low production cost, and is suitable for industrial production. Specifically, the para-substituted bromobenzene is prepared by taking bromobenzene as a raw material, carrying out Friedel-crafts acylation reaction on the bromobenzene and acyl chloride under the catalytic action of aluminum trichloride, and then carrying out Huang Minlon reaction on the bromobenzene.
In order to solve the above technical problem, the present application provides the following technical solutions.
In a first aspect, the present application provides a method for preparing para-substituted bromobenzene shown in formula 2, which is characterized in that the method comprises the following steps: in an organic solvent, in the presence of alkali, carrying out a Huang Minlon reaction on a compound shown as a formula 1 and hydrazine for a predetermined time period to obtain the para-substituted bromobenzene shown as a formula 2:
wherein R is selected from one or more of alkyl, halogenated alkyl, fluorinated alkyl, alkenyl, alkynyl, substituent substitution of carbocyclyl, heterocyclic radical, aryl, aralkyl, heteroaryl, heteroaralkyl, alkoxy, halogenated alkoxy, fluorinated alkoxy, alkenyloxy, alkynyloxy, carbocyclic oxy, heterocyclic oxy, aryloxy, aralkoxy, heteroaryloxy, heteroaralkoxy and amino.
In one embodiment of the first aspect, the organic solvent is a acetal solvent;
and/or, the hydrazine comprises hydrazine hydrate;
and/or, the volume-to-mass ratio of the organic solvent to the compound 1 is preferably 1mL/g to 30mL/g, more preferably 1mL/g to 10mL/g, for example 3 mL/g.
In one embodiment of the first aspect, the base comprises an inorganic base, preferably potassium hydroxide and/or sodium hydroxide.
In one embodiment of the first aspect, the molar ratio of the base to the compound 1 is preferably 1 to 10, more preferably 2 to 6, for example 3.
In one embodiment of the first aspect, compound 1 is prepared by the following method: carrying out Friedel-crafts acylation reaction on bromobenzene, Lewis acid and RCOCl to obtain the compound 1:
wherein R is as defined above.
In one embodiment of the first aspect, the lewis acid is preferably aluminum trichloride.
In one embodiment of the first aspect, the molar ratio of the lewis acid to the RCOCl is preferably 1 to 5, more preferably 1.0 to 1.5, for example 1.1;
and/or the molar ratio of bromobenzene to RCOCl is preferably 1-5, more preferably 1.1-2.5, such as 1.8.
In one embodiment of the first aspect, the temperature of the friedel-crafts acylation reaction is preferably-5 ℃ to 30 ℃, more preferably 0 ℃ to 25 ℃, such as 5 ℃ to 15 ℃ or 20 ℃ to 25 ℃.
In one embodiment of the first aspect, the time of the friedel-crafts acylation reaction is preferably 30 hours to 60 hours, further preferably 40 hours to 50 hours, such as 48 hours or 50 hours.
In one embodiment of the first aspect, magnesium powder is not used throughout the preparation of the para-substituted bromobenzene as shown in formula 2.
The application has the positive progress effects that: the preparation method has the advantages of good positioning effect, high purity of the prepared product, simple and safe operation, environmental friendliness and low production cost, and is suitable for industrial production.
Drawings
FIG. 1 is a GC spectrum of 1-bromo 4-isobutylbenzene according to example 1.
Detailed Description
Unless otherwise indicated, implied from the context, or customary in the art, all parts and percentages herein are by weight and the testing and characterization methods used are synchronized with the filing date of the present application. Where applicable, the contents of any patent, patent application, or publication referred to in this application are incorporated herein by reference in their entirety and their equivalent family patents are also incorporated by reference, especially as they disclose definitions relating to synthetic techniques, products and process designs, polymers, comonomers, initiators or catalysts, and the like, in the art. To the extent that a definition of a particular term disclosed in the prior art is inconsistent with any definitions provided herein, the definition of the term provided herein controls.
The numerical ranges in this application are approximations, and thus may include values outside of the ranges unless otherwise specified. A numerical range includes all numbers from the lower value to the upper value, in increments of 1 unit, provided that there is a separation of at least 2 units between any lower value and any higher value. For example, if a compositional, physical, or other property (e.g., molecular weight, melt index, etc.) is recited as 100 to 1000, it is intended that all individual values, e.g., 100, 101,102, etc., and all subranges, e.g., 100 to 166,155 to 170,198 to 200, etc., are explicitly recited. For ranges containing a numerical value less than 1 or containing a fraction greater than 1 (e.g., 1.1, 1.5, etc.), then 1 unit is considered appropriate to be 0.0001, 0.001, 0.01, or 0.1. For ranges containing single digit numbers less than 10 (e.g., 1 to 5), 1 unit is typically considered 0.1. these are merely specific examples of what is intended to be expressed and all possible combinations of numerical values between the lowest value and the highest value enumerated are to be considered to be expressly stated in this application.
When used with respect to chemical compounds, the singular includes all isomeric forms and vice versa (e.g., "hexane" includes all isomers of hexane, individually or collectively) unless expressly specified otherwise. In addition, unless explicitly stated otherwise, the use of the terms "a", "an" or "the" are intended to include the plural forms thereof.
The terms "comprising," "including," "having," and derivatives thereof do not exclude the presence of any other component, step or procedure, and are not intended to exclude the presence of other elements, steps or procedures not expressly disclosed herein. To the extent that any doubt is eliminated, all compositions herein containing, including, or having the term "comprise" may contain any additional additive, adjuvant, or compound, unless expressly stated otherwise. Rather, the term "consisting essentially of … …" excludes any other components, steps or processes from the scope of any of the terms hereinafter recited, except those necessary for performance. The term "consisting of … …" does not include any components, steps or processes not specifically described or listed. Unless explicitly stated otherwise, the term "or" refers to the listed individual members or any combination thereof.
Definition of terms
As used herein, the term "yield" refers to the amount of product obtained in a chemical reaction. The yield is usually expressed as a percentage of the theoretical yield of the reaction.
As used herein, the term "chromatography" is the subject of gel chromatography techniques, typically using glass or plexiglass tubes. A chromatographic method for separating components of a sample mixture by their different partition coefficients in a stationary phase and a mobile phase.
In one embodiment, the present application provides a method for preparing para-substituted bromobenzene shown in formula 2, which is characterized by comprising the following steps: in an organic solvent, under the condition of alkali, carrying out a Huang Minlon reaction on a compound shown as a formula 1 and hydrazine to obtain para-substituted bromobenzene shown as a formula 2;
wherein R is selected from amino, alkyl (e.g. C)1～C6Alkyl radical, said C1～C6Alkyl is preferably C1～C4Alkyl radical, said C1～C4The alkyl group can be methyl, ethyl, propyl, isopropyl, butylAlkyl, isobutyl or tert-butyl), alkoxy (e.g. C)1～C6Alkoxy radical, said C1～C6Alkoxy, preferably C1～C4Alkoxy radical, said C1～C4Alkoxy can be methoxy, ethoxy, propoxy, isopropyl, butyl, isobutyl, or tert-butyl), alkenyl (e.g., C2～C6Alkenyl), alkenyloxy, alkynyl (e.g. C)2～C6Alkynyl), alkynyloxy, cycloalkyl (e.g. C)3～C8Cycloalkyl radical, said C3～C8Cycloalkyl is preferably C3～C6Cycloalkyl radical, said C3～C6Cycloalkyl can be cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), carbocyclooxy, heterocyclooxy, aryl (e.g., C)5～C10Aryl), aryloxy, heteroaryloxy, heteroaryl (said heteroaryl preferably having O, S heteroatoms or N atoms, C having 1 to 3 heteroatoms)3～C6A heteroaryl group; the heteroatom is O, S or N atom, and the heteroatom number is 1-3C3～C6Heteroaryl "may be furyl; the furyl group may be
) A heterocyclic group (the heterocyclic group may be C having O, S or N atoms as a hetero atom and 1 to 3 hetero atoms3～C6A heterocyclic group); the alkyl and alkoxy groups may be optionally substituted with one or more of halo (e.g. fluoro, chloro, bromo or iodo), aryl, heteroaryl.
The preparation method of the para-substituted bromobenzene shown in the formula 2 can adopt a conventional method of the similar Huang Minlon reaction in the field, and the following reaction method and conditions are particularly preferred in the application:
in the preparation method of the para-substituted bromobenzene shown in the formula 2, the organic solvent is preferably an acetal solvent; the acetal solvent is preferably diethylene glycol.
In the preparation method of the para-substituted bromobenzene shown in the formula 2, the volume-to-mass ratio of the organic solvent to the compound 1 is preferably 1mL/g to 30mL/g, more preferably 1mL/g to 10mL/g, for example 3 mL/g.
In the preparation method of the para-substituted bromobenzene shown in the formula 2, the base is preferably an inorganic base, and the inorganic base is preferably potassium hydroxide and/or sodium hydroxide.
In the preparation method of para-substituted bromobenzene shown in formula 2, the molar ratio of the alkali to the compound 1 is preferably 1-10, more preferably 2-6, such as 3.
In the preparation method of para-substituted bromobenzene shown in formula 2, the hydrazine hydrate can be conventional commercial hydrazine hydrate reagent, the mass concentration of the hydrazine hydrate is preferably 40-80%, and the mass concentration refers to the percentage of the mass of hydrazine in the total mass of hydrazine hydrate solution.
In the preparation method of para-substituted bromobenzene shown in formula 2, the molar ratio of hydrazine to the compound 1 is preferably 1-10, more preferably 2-6, such as 3.
In the preparation method of the para-substituted bromobenzene shown in the formula 2, the temperature of the Huang Minlon reaction is preferably 70-130 ℃, more preferably 80-120 ℃, for example 110-120 ℃.
In the preparation method of the para-substituted bromobenzene shown in the formula 2, the progress of the Huang Minlon reaction can be monitored by a conventional monitoring method in the art (such as TLC, HPLC or NMR), the reaction system changes from reddish brown to pale yellow or lighter as the end point of the reaction, and the Huang Minlon reaction time is preferably 1 hour to 10 hours, more preferably 1 hour to 5 hours, such as 1 hour or 3 hours.
The preparation method of the para-substituted bromobenzene shown in the formula 2 preferably adopts the following reaction steps: and (2) dropwise adding hydrazine hydrate into a mixture of an organic solvent, alkali and the compound 1, carrying out reaction until the color of the system is reddish brown, distilling at normal pressure, and carrying out reflux reaction until the temperature of the system reaches about 180 ℃, thus obtaining the bromobenzene containing para-substitution shown in the formula 2. The temperature of the "mixture of the organic solvent, the base and the compound 1" is preferably 70 to 100 ℃, and more preferably 80 to 90 ℃. The dropping rate is preferably 100 g/hr to 500 g/hr, more preferably 150 g/hr to 350 g/hr, for example 267 g/hr.
The preparation method of the para-substituted bromobenzene shown in the formula 2 preferably adopts the following post-treatment steps: after the reaction is finished, crude products are obtained after extraction, washing and drying. The extraction, washing and drying can be carried out by methods conventional in the art for such procedures. The solvent used for extraction is preferably an ether solvent, and the ether solvent is preferably methyl tert-butyl ether. The number of times of extraction is preferably 1 to 3 times. The washing is preferably carried out with a saturated saline solution. The number of washing is preferably 1 to 3. The drying is preferably carried out by adopting a drying agent, and the drying agent is preferably anhydrous sodium sulfate.
The crude product is preferably rectified to obtain purified para-substituted bromobenzene shown in formula 2.
The preparation method of the para-substituted bromobenzene shown in the formula 2 preferably further comprises a preparation method of a compound 1, which comprises the following steps: carrying out Friedel-crafts acylation reaction on bromobenzene, Lewis acid and RCOCl to obtain the compound 1;
wherein R is as defined above.
Said compound 1 may be conventional in the art for this type of friedel-crafts acylation, the following reaction methods and conditions are particularly preferred in the present application:
in the preparation method of the compound 1, the Lewis acid is preferably aluminum trichloride.
In the preparation method of the compound 1, the molar ratio of the lewis acid to the RCOCl is preferably 1 to 5, more preferably 1.0 to 1.5, for example 1.1.
In the preparation method of the compound 1, the molar ratio of the bromobenzene to the RCOCl is preferably 1 to 5, more preferably 1.1 to 2.5, for example 1.8.
In the preparation method of the compound 1, the temperature of the friedel-crafts acylation reaction is preferably-5 ℃ to 30 ℃, and more preferably 0 ℃ to 25 ℃, for example, 5 ℃ to 15 ℃ or 20 ℃ to 25 ℃.
In the preparation method of the compound 1, the progress of the friedel-crafts acylation reaction can be monitored by a conventional monitoring method in the art (such as TLC, HPLC or NMR), and is generally the end point of the reaction when no hydrochloric acid gas escapes, and the time of the friedel-crafts acylation reaction is preferably 30 hours to 60 hours, more preferably 40 hours to 50 hours, such as 48 hours or 50 hours.
The preparation method of the compound 1 preferably adopts the following steps: and (3) dripping RCOCl into a mixture formed by bromobenzene and Lewis acid to carry out Friedel-crafts acylation reaction to obtain the compound 1. The temperature of the mixture of bromobenzene and Lewis acid is preferably-5 to 30 ℃, more preferably 0 to 20 ℃, for example 5 to 15 ℃. The dropping speed is based on maintaining the temperature of the reaction system not to exceed 15 ℃.
The preparation method of the compound 1 preferably adopts the following post-treatment steps: after the reaction is finished, quenching the reaction, extracting, washing, drying and removing the solvent to obtain a crude product. The crude product is preferably distilled to obtain a purified product.
Examples
The technical solutions of the present application will be clearly and completely described below with reference to the embodiments of the present application. The reagents and raw materials used are commercially available unless otherwise specified. The experimental methods without specifying specific conditions in the following examples were selected according to the conventional methods and conditions, or according to the commercial instructions.
Example 1
This example relates to the synthesis of 1-bromo-4-isobutylbenzene, which is synthesized as follows:
the first step is as follows:
the reaction equation is as follows:
the material ratio is as follows:
the specific experimental procedures of this example are as follows:
adding bromobenzene (1300g) and aluminum trichloride (688g) into a 5L four-opening bottle, controlling the temperature of an ice water bath to be 5-15 ℃, slowly dropwise adding isobutyryl chloride (500g) for about 1.5 hours, keeping the temperature at 5-15 ℃ for 1 hour, and reacting at the room temperature of 20-25 ℃ for 48 hours until no hydrochloric acid gas escapes.
The reaction solution is slowly poured into, for example, 2.5L of ice water to quench, and the layers are allowed to stand. Separating lower organic phase, extracting upper aqueous phase with methyl tert-butyl ether (2 × 1500ml) twice, and mixing organic phases; washed with saturated sodium bicarbonate (1000ml), saturated brine (500ml), then dried over anhydrous sodium sulfate (150g) and concentrated (water pump, 70 ℃ C. to remove solvent) to give crude 1- (4-bromophenyl) -2-methylpropan-1-one.
The vacuum degree of an oil pump is about 1mmHg, and the excess bromobenzene is distilled off at the external temperature of about 80 ℃.
And (3) distilling the product (the vacuum degree of an oil pump is about 1mmHg, the external temperature is 110-140 ℃), collecting the distillate at the temperature of a distillation head of 70-80 ℃, wherein the molar yield of the 1- (4-bromophenyl) -2-methylpropane-1-one is 66%, and the product content is more than 80% (one control).
The second step is that:
the reaction equation is as follows:
material proportioning:
the operation process is as follows:
adding diethylene glycol (2.25L), potassium hydroxide (585g) and 1- (4-bromophenyl) -2-methylpropane-1-ketone (790g) into a 5L four-mouth reaction bottle, and heating to 80-90 ℃; hydrazine hydrate (533g) is slowly added dropwise at a controlled temperature of 105-120 ℃ for about 2 hours. After the addition is finished, the temperature is kept at 110-120 ℃ for reaction for 1 hour, and the system is changed from light yellow to reddish brown. The reflux device is changed into normal pressure distillation, the system is slowly heated, excess hydrazine hydrate and water are evaporated, and meanwhile, partial products are evaporated. It took about 3 hours until the temperature in the system became more than 180 ℃ and the system became reddish brown to pale yellow or lighter in color. Then, the normal pressure distillation is changed into reflux, and the reaction is carried out for 1 hour at the temperature of 180-200 ℃. Then cooled to room temperature.
3.5L of water was added to the reaction system, stirred for 30 minutes, extracted three times with methyl tert-butyl ether (2X 1500mL +1000mL), the organic phases were combined, washed once with saturated brine (500mL), dried over anhydrous sodium sulfate and concentrated to give the crude product.
And (3) rectification: (about 1mmHg of an oil pump, the external temperature of 100-125 ℃) and 30cm of packed column, collecting the fraction with the temperature of 40-50 ℃ of a distillation head, obtaining 1-bromine 4-isobutylbenzene, (a central control unit), the molar yield is 52.8%, the product purity is 89.6%, and no other position isomer is detected. The GC pattern of the product is shown in FIG. 1.
Example 2
This example relates to the synthesis of 1-bromo-4- (cyclopentylmethyl) benzene, the synthetic route of which is shown below:
the procedure of example 1 was repeated except for changing isobutyryl chloride to cyclopentylchloride in the first step of example 1 to obtain 1-bromo-4- (cyclopentylmethyl) -benzene.
The procedure of this example was the same as that of example 1, except that 630g of cyclopentanecarbonyl chloride was used instead of isobutyryl chloride, to provide 4-bromophenyl cyclopentyl ketone in a first step in a molar yield of 63.2% and a product content of greater than 80%. The second step obtains 1-bromo-4- (cyclopentylmethyl) benzene, the molar yield is 52.0%, and the purity of the product is 92.3%.
Example 3
This example relates to the synthesis of 2- (4-bromobenzyl) furan, the synthetic route of which is shown below:
the procedure of example 1 was repeated except for changing isobutyryl chloride to furoyl chloride in the first step of example 1 to obtain 1-bromo-4- (furylmethyl) benzene.
The procedure of this example was identical to that of example 1, except that 623g of furoyl chloride was used instead of isobutyryl chloride, and the first step yielded 4-bromophenyl-2-furanone in 62.7% molar yield and a product content of greater than 80%. The second step obtains 2- (4-bromobenzyl) furan with a molar yield of 50.3% and a product purity of 90.6%.
Example 4
The products 1-bromo-4-isobutylbenzene, 1-bromo-4- (cyclopentylmethyl) benzene, and 2- (4-bromobenzyl) furan of examples 1 to 3 were reacted with magnesium chips, respectively, to prepare Grignard reagents, which were then reacted with alkyl borates, and hydrolyzed to obtain corresponding monoboronic acids, i.e., 4-isobutylphenylboronic acid, 4- (cyclopentylmethyl) phenylboronic acid, and 4- (furylmethyl) phenylboronic acid.
The embodiments described above are intended to facilitate the understanding and appreciation of the application by those skilled in the art. It will be readily apparent to those skilled in the art that various modifications to these embodiments may be made, and the generic principles described herein may be applied to other embodiments without the use of the inventive faculty. Therefore, the present application is not limited to the embodiments herein, and those skilled in the art who have the benefit of this disclosure will appreciate that many modifications and variations are possible within the scope of the present application without departing from the scope and spirit of the present application.
Claims (10)
1. A preparation method of para-substituted bromobenzene shown in formula 2 is characterized by comprising the following steps: in an organic solvent, in the presence of alkali, carrying out a Huang Minlon reaction on a compound shown as a formula 1 and hydrazine for a predetermined time period to obtain the para-substituted bromobenzene shown as a formula 2:
wherein R is selected from one or more of alkyl, halogenated alkyl, fluorinated alkyl, alkenyl, alkynyl, substituent substitution of carbocyclyl, heterocyclic radical, aryl, aralkyl, heteroaryl, heteroaralkyl, alkoxy, halogenated alkoxy, fluorinated alkoxy, alkenyloxy, alkynyloxy, carbocyclic oxy, heterocyclic oxy, aryloxy, aralkoxy, heteroaryloxy, heteroaralkoxy and amino.
2. The method for preparing para-substituted bromobenzene as shown in formula 2 in claim 1, wherein said organic solvent is a acetal solvent;
and/or, the hydrazine comprises hydrazine hydrate;
and/or, the volume-to-mass ratio of the organic solvent to the compound 1 is preferably 1mL/g to 30mL/g, more preferably 1mL/g to 10mL/g, for example 3 mL/g.
3. The method for preparing para-substituted bromobenzene as shown in formula 2 in claim 1, wherein said base comprises inorganic base, and said inorganic base is preferably potassium hydroxide and/or sodium hydroxide.
4. The method for preparing para-substituted bromobenzene as shown in formula 2 in claim 1, wherein the molar ratio of the base to the compound 1 is preferably 1-10, more preferably 2-6, such as 3.
5. The method for preparing para-substituted bromobenzene as shown in formula 2 in claim 1, wherein said compound 1 is prepared by the following method: carrying out Friedel-crafts acylation reaction on bromobenzene, Lewis acid and RCOCl to obtain the compound 1:
wherein R is as defined above.
6. The method for preparing para-substituted bromobenzene as shown in formula 2 in claim 5, wherein said Lewis acid is preferably aluminum trichloride.
7. The method for preparing para-substituted bromobenzene as shown in formula 2 in claim 5, wherein the molar ratio of Lewis acid to RCOCl is preferably 1-5, more preferably 1.0-1.5, such as 1.1;
and/or the molar ratio of bromobenzene to RCOCl is preferably 1-5, more preferably 1.1-2.5, such as 1.8.
8. The method for preparing para-substituted bromobenzene as shown in the formula 2 in claim 5, wherein the temperature of the Friedel-crafts acylation reaction is preferably-5 ℃ to 30 ℃, more preferably 0 ℃ to 25 ℃, such as 5 ℃ to 15 ℃ or 20 ℃ to 25 ℃.
9. The method for preparing para-substituted bromobenzene as shown in the formula 2 in claim 5, wherein the time of the Friedel-crafts acylation reaction is preferably 30 hours to 60 hours, more preferably 40 hours to 50 hours, such as 48 hours or 50 hours.
10. The method for preparing a para-substituted bromobenzene as set forth in any of claims 1 to 9, which does not use magnesium powder in the whole preparation process of the para-substituted bromobenzene as set forth in formula 2.
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