1, 4-dibromobenzene derivative and preparation and application thereof

Abstract

The invention relates to a 1, 4-dibromobenzene derivative as well as preparation and application thereof, and through a novel method for preparing the 1, 4-dibromobenzene derivative, a benzenediol derivative which is low in price and easy to obtain is taken as an initial raw material, a simple three-step cascade reaction is utilized, and the 1, 4-dibromobenzene derivative with high value is synthesized at the total yield of 90% or above. The method is simple in operation, simple in post-treatment, efficient in reaction and diversified. The preparation method overcomes the problem that a bromination method cannot control bromination sites, avoids harsh reaction conditions and expensive reaction reagents of Sandmeyer reaction, improves the reaction yield of coupling reaction, and solves the problem that complex 1, 4-dibromobenzene derivatives are difficult to prepare. The preparation method of the 1, 4-dibromobenzene derivative is green and environment-friendly, and has industrial application potential.

Description

Technical Field

[0001] The present disclosure relates to the technical fields of medical material chemistry and organic chemistry, and in particular to a 1,4-dibromobenzene derivative and a preparation method and application thereof. Background Art

[0002] Dibromobenzene is a general term for compounds obtained by replacing two hydrogen atoms on the benzene ring with bromine. There are three isomers due to the different substitution positions of bromine, namely 1,2-dibromobenzene, 1,3-dibromobenzene and 1,4-dibromobenzene. 1,4-Dibromobenzene derivatives are an important class of organic functional molecules, which are widely used in biomedicine, fine chemicals, organic optoelectronic materials and dyes. As important reaction intermediates, 1,4-dibromobenzene derivatives can be used as important key linkers to prepare various new materials with excellent properties (for example: J.Am.Chem.Soc.2016,138,14371-14379), which has very important potential application value.

[0003] The currently known methods for preparing 1,4-dibromobenzene derivatives are mainly the following: 1) direct bromination method; 2) preparation from bromoaniline substrates by Sandmeyer reaction; 3) preparation from disubstituted bromine atoms and iodine atoms by coupling reaction. However, the direct bromination method has the problem of being unable to effectively control the bromination site, and it is easy to generate a mixture of monobrominated and polybrominated products, resulting in low yield and difficult purification (for example, the invention patents with the following publication numbers: WO2024085749 or WO2020219411); the Sandmeyer reaction of bromoaniline substrates requires harsh reaction conditions and expensive reaction reagents, which is difficult to apply industrially; the preparation method from disubstituted bromine atoms and iodine atoms by coupling reaction has problems such as low yield and difficulty in preparing complex 1,4-dibromobenzene derivatives (for example, the invention patents with the following publication numbers: KR2020066572).

[0004] In summary, providing a new method for preparing 1,4-dibromobenzene derivatives has very important application value. Summary of the invention

[0005] In order to solve the above problems, the present application proposes a 1,4-dibromobenzene derivative, wherein the 1,4-dibromobenzene derivative has a chemical structural formula prepared by the following reaction steps:

[0006]

[0007] in:

[0008] R1 is selected from hydrogen, alkyl such as methyl and tert-butyl, halogen, trifluoromethyl, aryl or substituted aryl;

[0009] R2 is selected from hydrogen, alkyl such as methyl and tert-butyl, halogen, trifluoromethyl, aryl or substituted aryl;

[0010] R3 is selected from hydrogen, alkyl such as methyl and tert-butyl, halogen, trifluoromethyl, aryl or substituted aryl;

[0011] R4 is selected from hydrogen, alkanes such as methyl and tert-butyl, halogen, trifluoromethyl, aryl or substituted aryl.

[0012] On the other hand, the present application provides a method for preparing a 1,4-dibromobenzene derivative, comprising the following steps:

[0013] (a) using 1,4-benzenediol derivative A and trifluoromethanesulfonic anhydride as raw materials, reacting under the conditions of base 1 and solvent 1 at temperature 1 at a fixed time to prepare intermediate B;

[0014] (b) intermediate B and pinacol borane are used as raw materials, catalyzed by catalyst 1, reacted in the presence of base 2 and solvent 2 at temperature 2 to prepare intermediate C;

[0015] (c) Using intermediate C, catalyst 2 is used for catalysis, solvent 3 is used for reaction at temperature 3 for a fixed time to prepare a 1,4-dibromobenzene derivative.

[0016] As an optional embodiment of the present application, optionally, in step (a):

[0017] The molar ratio of the 1,4-benzenediol derivative A to the trifluoromethanesulfonic anhydride is 1:2-5;

[0018] The base 1 is one or more of the following: triethylamine, diethylamine, pyridine, sodium carbonate, potassium carbonate or diisopropylethylamine;

[0019] The solvent 1 is one or more of the following: dichloromethane, acetonitrile, ethyl acetate, chloroform, 1,4-dioxane or tetrahydrofuran;

[0020] The temperature 1 is 0-100° C.

[0021] The timed reaction is 1 to 10 hours.

[0022] As an optional embodiment of the present application, optionally, in step (b):

[0023] The molar ratio of the intermediate B to pinacol borane is 1:2-8;

[0024] The catalyst 1 is one or more of the following: palladium carbon, palladium acetate, 1,1'-bis(diphenylphosphino)ferrocene palladium dichloride dichloromethane complex, bis(acetonitrile)palladium chloride, palladium chloride, tetrakistriphenylphosphine palladium, bis(acetylacetone)palladium, allylpalladium chloride dimer, tris(dibenzylideneacetone)dipalladium, bis(tri-tert-butylphosphine)palladium, bis(dibenzylideneacetone)palladium or 1,1'-bis(diphenylphosphino)ferrocenepalladium dichloride;

[0025] The molar ratio of the intermediate B to the catalyst 1 is 1:0.02-0.001;

[0026] The base 2 is one or more of the following: triethylamine, diethylamine, pyridine, sodium carbonate, potassium carbonate or diisopropylethylamine;

[0027] The solvent 2 is one or more of the following: dichloromethane, acetonitrile, ethyl acetate, chloroform, 1,4-dioxane or tetrahydrofuran;

[0028] The temperature 2 is 0-150°C.

[0029] As an optional embodiment of the present application, optionally, in step (c):

[0030] The catalyst 2 is one or more of the following: copper bromide, cuprous bromide, palladium bromide;

[0031] The molar ratio of the intermediate C to the catalyst 2 is 1:2-10;

[0032] The solvent 2 is one or more of the following: dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, water, 1,4-dioxane, tetrahydrofuran or dimethyl sulfoxide;

[0033] The temperature 3 is 0 to 150° C.

[0034] The timed reaction is 1 to 48 hours.

[0035] As an optional embodiment of the present application, optionally, the solvent 2 is a mixed solvent of N,N-dimethylformamide, 1,4-dioxane and water, with a ratio of 1-6:1-2:1-2.

[0036] As an optional embodiment of the present application, optionally, the prepared 1,4-dibromobenzene derivative has any of the following chemical structural formulas D1-D7:

[0037]

[0038] On the other hand, the present application also provides an application of a 1,4-dibromobenzene derivative, wherein the 1,4-dibromobenzene derivative is used as a reaction intermediate in biomedicine or organic chemistry.

[0039] Technical effects of the present invention:

[0040] The novel method for preparing 1,4-dibromobenzene derivatives of the present invention uses cheap and readily available hydroquinone derivatives as starting materials and utilizes a simple three-step cascade reaction to synthesize high-value 1,4-dibromobenzene derivatives with a total yield of more than 90%.

[0041] The invention has simple operation, simple post-treatment, efficient reaction and diversity. The preparation method overcomes the problem that the bromination method cannot control the bromination site, avoids the harsh reaction conditions and expensive reaction reagents of the Sandmeyer reaction, improves the reaction yield of the coupling reaction, and solves the problem that the complex 1,4-dibromobenzene derivatives are difficult to prepare.

[0042] The invention provides a green and environmentally friendly preparation route of 1,4-dibromobenzene derivatives with industrial application potential.

[0043] Further features and aspects of the present disclosure will become apparent from the following detailed description of exemplary embodiments with reference to the attached drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0044] The accompanying drawings, which are incorporated in and constitute a part of the specification, illustrate exemplary embodiments, features, and aspects of the disclosure and, together with the description, serve to explain the principles of the disclosure.

[0045] Figure 1 The general structural formula of the 1,4-dibromobenzene derivative prepared by the present invention is:

[0046] Figure 2 According to the embodiment, 1,4-dibromobenzene derivative D1 1 H NMR (400MHz, CDCl3) hydrogen spectrum;

[0047] Figure 3 According to the embodiment of the present invention, 1,4-dibromobenzene derivative D1 13 C NMR (101MHz,CDCl3) carbon spectrum. DETAILED DESCRIPTION

[0048] Various exemplary embodiments, features and aspects of the present disclosure will be described in detail below with reference to the accompanying drawings. The same reference numerals in the accompanying drawings represent elements with the same or similar functions. Although various aspects of the embodiments are shown in the accompanying drawings, the drawings are not necessarily drawn to scale unless otherwise specified.

[0049] The word “exemplary” is used exclusively herein to mean “serving as an example, example, or illustration.” Any embodiment described herein as “exemplary” is not necessarily to be construed as preferred or advantageous over other embodiments.

[0050] In addition, in order to better illustrate the present disclosure, numerous specific details are given in the following specific embodiments. It should be understood by those skilled in the art that the present disclosure can also be implemented without certain specific details. In some examples, means, components and circuits well known to those skilled in the art are not described in detail in order to highlight the main purpose of the present disclosure.

[0051] The specific embodiments of the present invention will be further described below. The description of these embodiments is used to help understand the present invention, but does not constitute a limitation of the present invention. The experimental methods in the following examples are conventional methods unless otherwise specified, and the test materials used in the following examples are all available through conventional commercial channels unless otherwise specified.

[0052] The present invention provides a method for preparing the 1,4-dibromobenzene derivative according to claim 1, comprising the following steps:

[0053] (a) using 1,4-benzenediol derivative A and trifluoromethanesulfonic anhydride as raw materials, reacting under the conditions of base 1 and solvent 1 at temperature 1 at a fixed time to prepare intermediate B;

[0054] (b) intermediate B and pinacol borane are used as raw materials, catalyzed by catalyst 1, reacted in the presence of base 2 and solvent (2) at a timed reaction temperature of 2 to prepare intermediate C;

[0055] (c) Using intermediate C, catalyst 2 is used for catalysis, solvent 3 is used for reaction at temperature 3 for a fixed time to prepare a 1,4-dibromobenzene derivative.

[0056] The prepared 1,4-dibromobenzene derivative is prepared by the following reaction steps: Figure 1 The chemical structure shown is:

[0057]

[0058] in:

[0059] R1 is selected from hydrogen, alkyl such as methyl and tert-butyl, halogen, trifluoromethyl, aryl or substituted aryl;

[0060] R2 is selected from hydrogen, alkyl such as methyl and tert-butyl, halogen, trifluoromethyl, aryl or substituted aryl;

[0061] R3 is selected from hydrogen, alkyl such as methyl and tert-butyl, halogen, trifluoromethyl, aryl or substituted aryl;

[0062] R4 is selected from hydrogen, alkanes such as methyl and tert-butyl, halogen, trifluoromethyl, aryl or substituted aryl.

[0063] Please refer to the hydrogen and carbon spectra of the 1,4-dibromobenzene derivatives for details. Figure 2 and Figure 3 shown.

[0064] The preparation and structural formula of each embodiment of the 1,4-dibromobenzene derivative of the present invention will be described below.

[0065] In the reaction equations in the following embodiments, step means step, and each reaction condition, volume required for the reaction, etc. are marked in English. For example, CuBr2 is copper bromide, and its chemical name in Chinese and English has the same chemical definition, which is not limited in this embodiment.

[0066] Example 1---Preparation of 1,4-dibromobenzene derivative D1

[0067]

[0068] Step (a) Preparation of intermediate B1:

[0069] 1,4-Benzenediol derivative A1 (10 mmol, 1.0 eq), anhydrous dichloromethane (20 mL) and pyridine (40 mmol) were placed in a reactor, and trifluoromethanesulfonic anhydride (30 mmol, 3.0 eq) was slowly added dropwise under stirring. After reacting for 2 hours, a small amount of hydrochloric acid was added dropwise to quench the reaction, and the mixture was extracted with dichloromethane. The organic layers were combined, washed three times with saturated sodium bicarbonate aqueous solution, dried, filtered, concentrated under reduced pressure, and recrystallized to obtain intermediate B1 with a yield of 99%.

[0070] The characterization data of the intermediate B1 are: 1 H NMR (400MHz, CDCl3): δ = 7.44 (s, 2H), 1.41 (s, 18H).

[0071] Step (b) Preparation of intermediate C1:

[0072] Intermediate B1 (10 mmol, 1.0 eq), anhydrous 1,4-dioxane (10 mL) and 1,1'-bis(diphenylphosphino)ferrocenepalladium dichloride dichloromethane complex (10 mol%) were placed in a reactor, the reactor gas was replaced with nitrogen, and anhydrous 1,4-dioxane solution containing pinacol borane (1.16 mL, 8 mmol, 8.0 eq.) and triethylamine (1.112 mL, 8 mmol, 8.0 eq.) was slowly injected. After reacting at 80 degrees Celsius for 6 hours, water was added to quench the reaction, and the mixture was extracted with ethyl acetate. After combining the organic phases, the mixture was washed with water, dried, filtered, concentrated, and separated by column chromatography to obtain intermediate C1 with a yield of 99%.

[0073] The characterization data of the above intermediate C1 are: 1 H NMR (400MHz, CDCl3): δ=7.44 (s, 2H), 1.38 (s, 42H).

[0074] Step (c) Preparation of 1,4-dibromobenzene derivative product D1:

[0075] Intermediate C1 (10 mmol, 1.0 eq), copper bromide (60 mmol, 1.0 eq), N,N-dimethylformamide (20 mL), 1,4-dioxane (10 mL), and water (10 mL) were placed in a reactor. After reacting at 100 degrees Celsius for 24 hours, water was added to quench the reaction, and the mixture was extracted with ethyl acetate. The organic phases were combined, washed with water, dried, filtered, and concentrated in sequence. 1,4-dibromobenzene derivative D1 was obtained by column chromatography separation in a yield of 95%.

[0076] The characterization data of the above 1,4-dibromobenzene derivative D1 are: 1 H NMR (400MHz, CDCl3): δ = 7.59 (s, 2H), 1.48 (s, 18H). 13 C NMR (101MHz, CDCl3): δ=146.91, 135.01, 121.49, 36.04, 29.48.

[0077] Example 2---Preparation of 1,4-dibromobenzene derivative D2

[0078]

[0079] Step (a) Preparation of intermediate B2:

[0080] Prepared according to the method of preparing intermediate product B1 in Example 1.

[0081] The yield is 99%, and its characterization data are: 1H NMR (400MHz, CDCl3): δ=6.98 (s, 2H), 1.41 (s, 6H).

[0082] Step (b) Preparation of intermediate C2:

[0083] Prepared according to the method of preparing intermediate product C1 in Example 1.

[0084] The yield is 98%, and its characterization data are: 1 H NMR (400MHz, CDCl3): δ = 7.22 (s, 2H), 2.43 (s, 6H), 1.24 (s, 24H).

[0085] Step (c) Preparation of 1,4-dibromobenzene derivative product D2:

[0086] Prepared according to the method for preparing intermediate product D1 in Example 1.

[0087] The yield is 96%, and its characterization data are: 1 H NMR (400MHz, CDCl3): δ=7.38 (s, 2H), 2.32 (s, 6H).

[0088] Example 3---Preparation of 1,4-dibromobenzene derivative D3

[0089]

[0090] Step (a) Preparation of intermediate B3:

[0091] Prepared according to the method of preparing intermediate product B1 in Example 1.

[0092] The yield is 99%, and its characterization data are: 1 H NMR (400MHz, CDCl3): δ=6.99 (s, 2H).

[0093] Step (b) Preparation of intermediate C3:

[0094] Prepared according to the method of preparing intermediate product C1 in Example 1.

[0095] The yield is 99%, and its characterization data are: 1 H NMR (400MHz, CDCl3): δ=7.31 (s, 2H), 1.36 (s, 24H).

[0096] Step (c) Preparation of 1,4-dibromobenzene derivative product D3:

[0097] Prepared according to the method for preparing intermediate product D1 in Example 1.

[0098] The yield is 95%, and its characterization data are: 1 H NMR (400MHz, CDCl3): δ = 7.42 (s, 2H).

[0099] Example 4---Preparation of 1,4-dibromobenzene derivative D4

[0100]

[0101] Step (a) Preparation of intermediate B4:

[0102] Prepared according to the method of preparing intermediate product B1 in Example 1.

[0103] The yield is 99%, and its characterization data are: 1 H NMR (400MHz, CDCl3): δ=7.55 (s, 2H).

[0104] Step (b) Preparation of intermediate C4:

[0105] Prepared according to the method of preparing intermediate product C1 in Example 1.

[0106] The yield is 99%, and its characterization data are: 1 H NMR (400MHz, CDCl3): δ=7.99 (s, 2H), 1.37 (s, 24H).

[0107] Step (c) Preparation of 1,4-dibromobenzene derivative product D4:

[0108] Prepared according to the method for preparing intermediate product D1 in Example 1.

[0109] The yield is 96%, and its characterization data are: 1 H NMR (400MHz, CDCl3): δ = 8.01 (s, 2H).

[0110] Example 5---Preparation of 1,4-dibromobenzene derivative D5

[0111]

[0112] Step (a) Preparation of intermediate B5:

[0113] Prepared according to the method of preparing intermediate product B1 in Example 1.

[0114] The yield is 99%, and its characterization data are: 1 H NMR (400MHz, CDCl3): δ=7.46-7.53 (m, 12H).

[0115] Step (b) Preparation of intermediate C5:

[0116] Prepared according to the method of preparing intermediate product C1 in Example 1.

[0117] The yield is 96%, and its characterization data are: 1 H NMR (400MHz, CDCl3): δ=7.45-7.52 (m, 12H), 1.32 (s, 24H).

[0118] Step (c) Preparation of 1,4-dibromobenzene derivative product D5:

[0119] Prepared according to the method for preparing intermediate product D1 in Example 1.

[0120] The yield is 96%, and its characterization data are: 1 H NMR (400MHz, CDCl3): δ=7.65 (s, 2H), 7.47-7.42 (m, 10H).

[0121] Example 6---Preparation of 1,4-dibromobenzene derivative D6

[0122]

[0123] Step (a) Preparation of intermediate B6:

[0124] Prepared according to the method of preparing intermediate product B1 in Example 1.

[0125] The yield is 99%, and its characterization data are: 1 H NMR (400MHz, CDCl3): δ=7.99-7.94(m,2H), 7.91-7.86(m,4H), 7.75-7.72(m,2H), 7.53-7.47(m,6H), 7.44(s,24H).

[0126] Step (b) Preparation of intermediate C6:

[0127] Prepared according to the method of preparing intermediate product C1 in Example 1.

[0128] The yield is 97%, and its characterization data are: 1 H NMR (400MHz, CDCl3): δ=7.99-7.94(m,2H),7.91-7.86(m,4H),7.75-7.72(m,2H),7.53-7.47(m,6H),7.44(s,24H),1.28(s,24H).

[0129] Step (c) Preparation of 1,4-dibromobenzene derivative product D6:

[0130] Prepared according to the method for preparing intermediate product D1 in Example 1.

[0131] The yield is 96%, and its characterization data are: 1 H NMR (400MHz, CDCl3): δ=7.95-7.90 (m, 4H), 7.78 (s, 2H), 7.61 (dd, 2H, J=8.2, 1.8Hz), 7.56-7.54 (m, 4H).

[0132] Example 7---Preparation of 1,4-dibromobenzene derivative D7

[0133]

[0134] Step (a) Preparation of intermediate B7:

[0135] Prepared according to the method of preparing intermediate product B1 in Example 1.

[0136] The yield is 99%, and its characterization data are: 1 H NMR (400MHz, CDCl3): δ=7.76 (s, 2H), 7.74-7.46 (m, 18H).

[0137] Step (b) Preparation of intermediate C7:

[0138] Prepared according to the method of preparing intermediate product C1 in Example 1.

[0139] The yield is 95%, and its characterization data are: 1 H NMR (400MHz, CDCl3): δ=7.66 (s, 2H), 7.54-7.26 (m, 18H).

[0140] Step (c) Preparation of 1,4-dibromobenzene derivative product D7:

[0141] Prepared according to the method for preparing intermediate product D1 in Example 1.

[0142] The yield is 92%, and its characterization data are: 1 H NMR (400MHz, CDCl3): 7.68 (s, 2H), 7.64-7.36 (m, 18H).

[0143] The above embodiments are preferred implementation modes of the present invention, but the implementation modes of the present invention are not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications made without departing from the spirit and principles of the present invention shall be equivalent replacement methods and shall be included in the protection scope of the present invention.

[0144] The embodiments of the present disclosure have been described above, and the above description is exemplary, not exhaustive, and is not limited to the disclosed embodiments. Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the described embodiments. The selection of terms used herein is intended to best explain the principles of the embodiments, practical applications, or technical improvements to the technology in the market, or to enable other persons of ordinary skill in the art to understand the embodiments disclosed herein.

Claims

1. A 1,4-dibromobenzene derivative, characterized in that: The 1,4-dibromobenzene derivative has a chemical structural formula prepared by the following reaction steps: in: R1 is selected from hydrogen, methyl, tert-butyl alkane, halogen, trifluoromethyl, aryl or substituted aryl; R2 is selected from hydrogen, methyl, tert-butyl alkane, halogen, trifluoromethyl, aryl or substituted aryl; R3 is selected from hydrogen, methyl, tert-butyl alkane, halogen, trifluoromethyl, aryl or substituted aryl; R4 is selected from hydrogen, methyl, tert-butyl alkane, halogen, trifluoromethyl, aryl or substituted aryl.

2. A method for preparing the 1,4-dibromobenzene derivative according to claim 1, characterized in that: The steps include: (a) using 1,4-benzenediol derivative A and trifluoromethanesulfonic anhydride as raw materials, reacting in the presence of a base (1) and a solvent (1) at a temperature (1) to prepare an intermediate B; (b) using intermediate B and pinacol borane as raw materials, catalyzed by catalyst (1), reacting in the presence of base (2) and solvent (2) at temperature (2) for a fixed time to prepare intermediate C; (c) Intermediate C is catalyzed by catalyst (2), in solvent (3), and reacted at temperature (3) to obtain a 1,4-dibromobenzene derivative.

3. The preparation method according to claim 2, characterized in that: In step (a): The molar ratio of the 1,4-benzenediol derivative A to the trifluoromethanesulfonic anhydride is 1:2-5; The base (1) is one or more of the following: triethylamine, diethylamine, pyridine, sodium carbonate, potassium carbonate or diisopropylethylamine; The solvent (1) is one or more of the following: dichloromethane, acetonitrile, ethyl acetate, chloroform, 1,4-dioxane or tetrahydrofuran; The temperature (1) is 0 to 100° C.; The timed reaction is 1 to 10 hours.

4. The preparation method according to claim 2, characterized in that: In step (b): The molar ratio of the intermediate B to pinacol borane is 1:2-8; The catalyst (1) is one or more of the following: palladium on carbon, palladium acetate, 1,1'-bis(diphenylphosphino)ferrocene palladium dichloride dichloromethane complex, bis(acetonitrile)palladium chloride, palladium chloride, tetrakistriphenylphosphine palladium, bis(acetylacetone)palladium, allylpalladium chloride dimer, tris(dibenzylideneacetone)dipalladium, bis(tri-tert-butylphosphine)palladium, bis(dibenzylideneacetone)palladium or 1,1'-bis(diphenylphosphino)ferrocenepalladium dichloride; The molar ratio of the intermediate B to the catalyst (1) is 1:0.02-0.001; The base (2) is one or more of the following: triethylamine, diethylamine, pyridine, sodium carbonate, potassium carbonate or diisopropylethylamine; The solvent (2) is one or more of the following: dichloromethane, acetonitrile, ethyl acetate, chloroform, 1,4-dioxane or tetrahydrofuran; The temperature (2) is 0 to 150°C.

5. The preparation method according to claim 2, characterized in that: In step (c): The catalyst (2) is one or more of the following: copper bromide, cuprous bromide, palladium bromide; The molar ratio of the intermediate C to the catalyst (2) is 1:2-10; The solvent (2) is one or more of the following: dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, water, 1,4-dioxane, tetrahydrofuran or dimethyl sulfoxide; The temperature (3) is 0 to 150° C.; The timed reaction is 1 to 48 hours.

6. The preparation method according to claim 5, characterized in that: The solvent (2) is a mixed solvent of N,N-dimethylformamide, 1,4-dioxane and water, with a ratio of 1-6:1-2:1-2.

7. The preparation method according to claim 2, characterized in that: The prepared 1,4-dibromobenzene derivative has any of the following chemical structural formulas D1-D7:

8. An application of the 1,4-dibromobenzene derivative according to claim 1, characterized in that: The 1,4-dibromobenzene derivative is used as a reaction intermediate in biomedicine or organic chemistry.

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