Method for preparing (1-bromo-2-(arylsulfonyl) ethyl) aromatic hydrocarbon by solid-phase chemical method
By solid-phase chemistry, sodium arylsulfinate and copper bromide react with aryl olefins under ball milling conditions, the problem of low solvent use and yield in the synthesis of sulfone compound in the prior art is solved, and high Preparation of purity, safe and environmentally friendly (1-bromo-2-(aromatic sulfonyl)ethyl) aromatic hydrocarbons.
Patent Information
- Application Number
- CN202411325707.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-09-23
- Publication Date
- 2024-12-27
AI Technical Summary
In the prior art, the synthesis method of sulfone-based compounds has problems such as the use of flammable, toxic solvents, product impurities and low yields, making it difficult to achieve green organic synthesis.
Using solid phase chemistry, sodium arylsulfinate and copper bromide react with aryl olefins under ball milling conditions to avoid the use of solvents, and promote solid phase interface reaction through mechanical ball milling to prepare (1-bromo-2-(aromatics) sulfonyl)ethyl)aromatic hydrocarbon.
A mild reaction without solvent participation was achieved, and the synthesis was completed in a short time. The purity of the product reached 99.0% or above, which was safe and environmentally friendly, and in line with the concept of green organic synthesis.
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Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of synthesis of sulfone organic compounds, and specifically relates to a method for preparing (1-bromo-2-(arylsulfonyl)ethyl)arene by a solid phase chemical method. Background Art
[0002] Sulfone is an important group in organic chemistry. The introduction of sulfone groups into organic molecules can have a significant impact on the physical, chemical and pharmaceutical properties of the compounds. According to statistics, sulfone groups are "high-frequency structures" in small molecule chemical drugs, ranking fourth in frequency of occurrence after phenylpropyl, phenylethylamine and phenyl ether skeletons. Currently, the number of sulfone-containing drugs approved for marketing by the US Food and Drug Administration exceeds ninety. At the same time, sulfone groups are also widely used in polymer materials. For example, polysulfone is a thermoplastic resin containing sulfone groups (-SO2-) and arylene groups in the main chain of the molecule. This type of resin has high hardness and impact strength, is non-toxic, has good heat resistance, cold resistance and aging resistance, and has flame retardancy and self-extinguishing properties. It can be used for a long time at -100 to 175°C.
[0003]
[0004] In view of the wide application of sulfone structures in many fields such as medicinal chemistry and materials science, the development of green organic synthesis methods for sulfone compounds is of great practical significance. There are currently three main synthetic routes for sulfone compounds: (1) constructing sulfone structures through oxidation of sulfide; (2) constructing sulfone structures through insertion of sulfur dioxide and formation of two carbon-sulfur bonds; (3) constructing sulfone structures by introducing hydrocarbon sulfinates as sulfone building blocks into organic molecular skeletons. It should be pointed out that the first route uses strong oxidants (hydrogen peroxide, m-chloroperbenzoic acid, etc.) to achieve oxidation of sulfide, which has poor compatibility with other sensitive functional groups; the second route requires the use of sulfur dioxide reagents, which are toxic, difficult to operate, and difficult to control selectivity when forming two carbon-sulfur bonds; the advantage of the third route is that the aryl sulfone building blocks are directly derived from sodium aryl sulfinates, the reagents are easy to obtain and handle, and the organic molecule receptors are widely diverse.
[0005] Bromine, as one of the halogens, also plays an important role in drug research and development. According to the survey, there are more than 250 bromine-containing drugs currently approved, and the molecular formulas of some bromine-containing drugs are as follows.
[0006]
[0007] Therefore, developing a strategy to simultaneously introduce bromine and sulfone groups into organic molecules will undoubtedly give full play to the regulatory advantages of bromine and sulfone groups on drug activity and play a beneficial role in the discovery of lead compounds and drugs.
[0008] As an example of adjacent modification of bromine and sulfone groups on the carbon skeleton, the existing direct synthesis methods of (1-bromo-2-(arylsulfonyl)ethyl)arene are mainly: (1) benzenesulfonyl bromide and aromatic olefins directly undergo addition reaction at 80°C; (2) phenylsulfinic acid and aromatic olefins react with N-bromosuccinimide (NBS) to generate the target product (Tetrahedron Letters, 2015, 56, 1808-1811); (3) sodium arylsulfinate and aromatic olefins react with bromine to prepare (1-bromo-2-(arylsulfonyl)ethyl)arene (Tetrahedron, 1980, 36, 2483-2487). It should be pointed out that methods (1) and (2) need to be carried out under heating conditions and use benzenesulfonyl bromide or N-bromosuccinimide, which are difficult to handle. Method (3) needs to use toxic and volatile elemental bromine and the product is impure and the yield is low. Finally, the above methods all require the use of a large amount of flammable and toxic organic solvents as reaction media, which poses considerable risks in terms of reaction safety and environmental protection.
[0009] Based on some limitations of traditional methods, it is urgent to seek new technologies for the preparation of (1-bromo-2-(arylsulfonyl)ethyl)arene that conform to the concept of green organic synthesis, so as to provide a reference for the rapid introduction of pharmacodynamic modification groups into organic molecular skeletons. Summary of the invention
[0010] The purpose of the present invention is to overcome the deficiencies in the prior art, bypass the traditional solution phase synthesis reaction route, avoid the use of reaction solvents, and provide a method for preparing (1-bromo-2-(arylsulfonyl)ethyl)arene by solid phase chemical method. In the method, the solid material properties of sodium arylsulfinate and copper bromide are utilized, aryl olefins are added, and then ball milling reaction is carried out under solid phase conditions. The entire reaction conditions are mild, the reaction time is short, the reaction process does not involve solvents, and the solvents used for separation and purification are safe, which is in line with the development direction of green organic synthesis.
[0011] In order to achieve the above invention object, the specific technical solution of the present invention is:
[0012] A method for preparing (1-bromo-2-(arylsulfonyl)ethyl)arene by solid phase chemical method comprises the following steps: adding aryl olefin, sodium arylsulfinate and copper bromide into a ball mill under air atmosphere; closing the ball mill and subjecting the above substances to ball milling reaction for a certain period of time to obtain (1-bromo-2-(arylsulfonyl)ethyl)arene.
[0013] As a better embodiment of the present application, in the method for preparing (1-bromo-2-(arylsulfonyl)ethyl)arene by a solid phase chemical method, the molar ratio of the aromatic olefin, the sodium aromatic sulfinate and the copper bromide is 1:1.2-1.5:2.4-3.0.
[0014] As a better embodiment of the present application, in the method for preparing (1-bromo-2-(arylsulfonyl)ethyl)arene by a solid phase chemical method, the molar ratio of the aromatic olefin, the sodium aromatic sulfinate and the copper bromide is more preferably 5:6:12.
[0015] As a better embodiment of the present application, in the method for preparing (1-bromo-2-(arylsulfonyl)ethyl)arene by a solid phase chemical method, the material of the ball mill is 304 stainless steel or zirconium oxide.
[0016] As a better embodiment of the present application, in the method for preparing (1-bromo-2-(arylsulfonyl)ethyl)arene by a solid phase chemical method, the ball milling reaction time is 2 hours or more.
[0017] As a better embodiment of the present application, in the method for preparing (1-bromo-2-(arylsulfonyl)ethyl)arene by a solid phase chemical method, the aromatic olefins include but are not limited to styrene, 4-tert-butylstyrene, 2-vinylnaphthalene, and 4-vinylbiphenyl.
[0018] As a better embodiment of the present application, in the method for preparing (1-bromo-2-(arylsulfonyl)ethyl)arene by a solid phase chemical method, the sodium aryl sulfinate includes but is not limited to sodium phenylsulfinate, sodium p-chlorophenylsulfinate, and sodium p-toluenesulfinate.
[0019] As a better embodiment of the present application, the method for preparing (1-bromo-2-(arylsulfonyl)ethyl)arene by a solid phase chemical method also includes a separation and purification step.
[0020] As a better embodiment of the present application, in the method for preparing (1-bromo-2-(arylsulfonyl)ethyl)arene by a solid phase chemical method, the specific operation of the separation and purification step is: after the ball milling reaction is completed, the product is dissolved in ethyl acetate, filtered and the filter residue is removed to obtain an ethyl acetate solution containing (1-bromo-2-(arylsulfonyl)ethyl)arene; then the solvent is concentrated to remove, and then ethanol is used as a solvent for recrystallization and purification, and finally (1-bromo-2-(arylsulfonyl)ethyl)arene is obtained.
[0021] In the present application, a solid phase chemical reaction is used, which refers to the process of solid-solid reaction to generate a solid product. Mechanical ball milling is used to promote diffusion, molecular transfer and reaction on the solid phase interface, thereby achieving a route different from traditional solution phase synthesis.
[0022] Compared with the prior art, the present invention has the following beneficial effects:
[0023] (i) In this method, mechanical ball milling is used for solid phase synthesis, which avoids the use of flammable, toxic, and volatile reaction solvents and saves the cost of reaction solvents.
[0024] (ii) The method adopted in the present invention does not require the addition of materials under an inert protective gas atmosphere, does not require a heating device, is easy to operate, and has simple steps.
[0025] (III) The target product of the reaction of the present invention is soluble in an organic solvent and can be easily separated from the reaction raw materials and the inorganic salts of the accompanying products, and the separation and purification are simple; the purity of the purified product reaches 99.0% or more. DETAILED DESCRIPTION
[0026] In order to make the purpose, technical scheme and advantages of the present invention clearer, the present invention is further described in detail below in conjunction with examples. It should be understood that the specific examples described herein are only used to explain the present invention and are not intended to limit the present invention. In addition, it should be understood that after reading the content of the present invention, those skilled in the art can make various changes and modifications to the present invention, but these equivalent forms also fall within the scope defined by the claims attached to the application.
[0027] The following is a detailed description of a method for preparing (1-bromo-2-(arylsulfonyl)ethyl)arene by a solid phase chemical method of the present invention in combination with specific principles and preparation processes.
[0028] Example 1: Preparation of (1-bromo-2-(phenylsulfonyl)ethyl)benzene by solid phase chemical method using styrene, sodium phenylsulfinate and copper bromide
[0029] The chemical reaction formula for preparing the compound (1-bromo-2-(phenylsulfonyl)ethyl)benzene in this example is as follows:
[0030]
[0031] The specific preparation process is as follows:
[0032] Under air atmosphere, sodium phenylsulfinate (0.985 g, 6.0 mmol), copper bromide (2.680 g, 12.0 mmol), styrene (0.521 g, 5.0 mmol) were weighed into a 10 mL ball mill (304 stainless steel material), and 1 304 stainless steel bead with a diameter of 1 cm was added (to play a ball milling role), and the ball mill was closed and covered. The ball mill was placed in a ball mill, and ball milling was performed 4 times according to the procedure of ball milling for 30 minutes / pause for 5 minutes and a frequency of 30 Hz, for a total of 2 hours. The reaction was stopped, 10 ml of ethyl acetate was added to the ball mill to dissolve the product, and the product was filtered, and the ball mill and solid residue were washed with 10 ml of ethyl acetate, and the ethyl acetate filtrate was combined. The ethyl acetate was concentrated to remove the ethyl acetate, and ethanol (7 mL) was used as a solvent for recrystallization to obtain (1-bromo-2-(phenylsulfonyl)ethyl)benzene (1.302 g, 4.0 mmol), with a yield of 80% (purity 99.2%).
[0033] The structural data of the product prepared in this example are characterized as follows:
[0034] 1 H NMR (600MHz, CDCl3) δ7.74 (d, J=7.6Hz, 2H), 7.57 (q, J=7.6Hz, 1H), 7.43 (dd, J= 16.1, 8.2Hz, 2H), 7.26 (s, 5H), 5.34 (t, J = 6.9Hz, 1H), 3.95 (s, 1H), 3.87 (s, 1H).
[0035] Example 2: Preparation of (1-bromo-2-(phenylsulfonyl)ethyl)benzene by solid phase chemical method using styrene, sodium phenylsulfinate and copper bromide
[0036] The chemical reaction formula for preparing the compound (1-bromo-2-(phenylsulfonyl)ethyl)benzene in this example is as follows:
[0037]
[0038] The specific preparation process is as follows:
[0039] Under air atmosphere, sodium phenylsulfinate (0.985 g, 6.0 mmol), copper bromide (3.306 g, 14.8 mmol), styrene (0.521 g, 5.0 mmol) were weighed into a 10 mL ball mill (304 stainless steel material), and 1 304 stainless steel bead with a diameter of 1 cm (for ball milling) was added, and the ball mill was closed and covered. The ball mill was placed in a ball mill, and ball milling was performed 4 times according to the procedure of ball milling for 30 minutes / pause for 5 minutes and a frequency of 30 Hz for a total of 2 hours. The reaction was stopped, 10 ml of ethyl acetate was added to the ball mill to dissolve the product, and the product was filtered, and the ball mill and solid residue were washed with 10 ml of ethyl acetate, and the ethyl acetate filtrate was combined. The ethyl acetate was concentrated to remove the ethyl acetate, and ethanol (7 mL) was used as a solvent for recrystallization to obtain (1-bromo-2-(phenylsulfonyl)ethyl)benzene (1.220 g, 3.75 mmol), with a yield of 75% (purity 99.1%).
[0040] Example 3: Preparation of (1-bromo-2-(phenylsulfonyl)ethyl)benzene by solid phase chemical method using styrene, sodium phenylsulfinate and copper bromide
[0041] The chemical reaction formula for preparing the compound (1-bromo-2-(phenylsulfonyl)ethyl)benzene in this example is as follows:
[0042]
[0043] The specific preparation process is as follows:
[0044] Under air atmosphere, sodium phenylsulfinate (1.231 g, 7.5 mmol), copper bromide (3.350 g, 15.0 mmol), styrene (0.521 g, 5.0 mmol) were weighed into a 10 mL ball mill (304 stainless steel material), and 1 304 stainless steel bead with a diameter of 1 cm (for ball milling) was added, and the ball mill was closed and covered. The ball mill was placed in a ball mill, and ball milling was performed 4 times according to the procedure of ball milling for 30 minutes / pause for 5 minutes and a frequency of 30 Hz for a total of 2 hours. The reaction was stopped, 10 ml of ethyl acetate was added to the ball mill to dissolve the product, and the product was filtered, and the ball mill and solid residue were washed with 10 ml of ethyl acetate, and the ethyl acetate filtrate was combined. The ethyl acetate was concentrated to remove the ethyl acetate, and ethanol (7 mL) was used as a solvent for recrystallization to obtain (1-bromo-2-(phenylsulfonyl)ethyl)benzene (1.187 g, 3.65 mmol), with a yield of 73% (purity 99.3%).
[0045] Example 4: Preparation of (1-bromo-2-(phenylsulfonyl)ethyl)benzene by solid phase chemical method using styrene, sodium phenylsulfinate and copper bromide
[0046] The chemical reaction formula for preparing the compound (1-bromo-2-(phenylsulfonyl)ethyl)benzene in this example is as follows:
[0047]
[0048] The specific preparation process is as follows:
[0049] Under air atmosphere, sodium phenylsulfinate (0.985 g, 6.0 mmol), copper bromide (2.680 g, 12.0 mmol), styrene (0.521 g, 5.0 mmol) were weighed into a 10 mL ball mill (304 stainless steel material), and 1 304 stainless steel bead with a diameter of 1 cm was added (to play a ball milling role), and the ball mill was closed and covered. The ball mill was placed in a ball mill, and ball milling was performed 6 times according to the procedure of ball milling for 30 minutes / pause for 5 minutes and a frequency of 30 Hz, for a total of 3 hours. The reaction was stopped, 10 ml of ethyl acetate was added to the ball mill to dissolve the product, and the product was filtered, and the ball mill and solid residue were washed with 10 ml of ethyl acetate, and the ethyl acetate filtrate was combined. The ethyl acetate was concentrated to remove the ethyl acetate, and ethanol (7 mL) was used as a solvent for recrystallization to obtain (1-bromo-2-(phenylsulfonyl)ethyl)benzene (1.366 g, 4.2 mmol), with a yield of 84% (purity 99.4%).
[0050] Example 5: Preparation of (1-bromo-2-(phenylsulfonyl)ethyl)benzene by solid phase chemical method using styrene, sodium phenylsulfinate and copper bromide
[0051] The chemical reaction formula for preparing the compound (1-bromo-2-(phenylsulfonyl)ethyl)benzene in this example is as follows:
[0052]
[0053] The specific preparation process is as follows:
[0054] Under air atmosphere, sodium phenylsulfinate (0.985 g, 6.0 mmol), copper bromide (2.680 g, 12.0 mmol), styrene (0.521 g, 5.0 mmol) were weighed into a 10 mL ball mill (made of zirconium oxide), and finally a 304 stainless steel bead with a diameter of 1 cm (for ball milling) was added, and the ball mill was closed and covered. The ball mill was placed in a ball mill, and ball milling was performed 6 times according to the procedure of ball milling for 30 minutes / pause for 5 minutes and a frequency of 30 Hz, for a total of 3 hours. The reaction was stopped, 10 ml of ethyl acetate was added to the ball mill to dissolve the product, and the product was filtered, and the ball mill and solid residue were washed with 10 ml of ethyl acetate, and the ethyl acetate filtrate was combined. The ethyl acetate was concentrated to remove the ethyl acetate, and ethanol (7 mL) was used as a solvent for recrystallization to obtain (1-bromo-2-(phenylsulfonyl)ethyl)benzene (1.333 g, 4.1 mmol), with a yield of 82% (purity 99.2%).
[0055] Example 6: Preparation of 1-(1-bromo-2-(phenylsulfonyl)ethyl)-4-tert-butylbenzene by solid phase chemical method using 4-tert-butylstyrene, sodium phenylsulfinate and copper bromide
[0056] The chemical reaction formula for preparing the compound 1-(1-bromo-2-(phenylsulfonyl)ethyl)-4-tert-butylbenzene in this example is as follows:
[0057]
[0058] The specific preparation process is as follows:
[0059] Under air atmosphere, sodium phenylsulfinate (0.985 g, 6.0 mmol), copper bromide (2.680 g, 12.0 mmol), 4-tert-butylstyrene (0.801 g, 5.0 mmol) were weighed into a 10 mL ball mill (304 stainless steel material), and 1 304 stainless steel bead with a diameter of 1 cm (for ball milling) was added, and the ball mill was closed and covered. The ball mill was placed in a ball mill, and ball milling was performed 6 times according to the procedure of ball milling for 30 minutes / pause for 5 minutes and a frequency of 30 Hz for a total of 3 hours. The reaction was stopped, 10 ml of ethyl acetate was added to the ball mill to dissolve the product, and the product was filtered, and the ball mill and solid residue were washed with 10 ml of ethyl acetate, and the ethyl acetate filtrate was combined. The ethyl acetate was removed by concentration, and 1-(1-bromo-2-(phenylsulfonyl)ethyl)-4-tert-butylbenzene (1.449 g, 3.8 mmol) was obtained by recrystallization using ethanol (7 mL) as solvent. The yield was 76% (purity 99.0%).
[0060] 1 H NMR (600MHz, CDCl3) δ7.56(d,J=7.3Hz,2H),7.40(t,J=7.5Hz,1H),7.26(t,J=7.9Hz,2H),7 .15-6.98(m,4H),5.20(t,J=7.0Hz,1H),3.88-3.80(m,1H),3.79-3.73(m,1H),1.13(s,9H).
[0061] Example 7: Preparation of 2-(1-bromo-2-(phenylsulfonyl)ethyl)naphthalene by solid phase chemical method using 2-vinylnaphthalene, sodium phenylsulfinate and copper bromide
[0062] The chemical reaction formula for preparing the compound 2-(1-bromo-2-(phenylsulfonyl)ethyl)naphthalene in this example is as follows:
[0063]
[0064] The specific preparation process is as follows:
[0065] Under air atmosphere, sodium phenylsulfinate (0.985 g, 6.0 mmol), copper bromide (2.680 g, 12.0 mmol), 2-vinylnaphthalene (0.771 g, 5.0 mmol) were weighed into a 10 mL ball mill (304 stainless steel material), and finally 1 304 stainless steel bead with a diameter of 1 cm (for ball milling) was added, and the ball mill was closed and covered. The ball mill was placed in a ball mill, and ball milling was performed 6 times according to the procedure of ball milling for 30 minutes / pause for 5 minutes and a frequency of 30 Hz for a total of 3 hours. The reaction was stopped, 10 ml of ethyl acetate was added to the ball mill to dissolve the product, and the product was filtered, and the ball mill and solid residue were washed with 10 ml of ethyl acetate, and the ethyl acetate filtrate was combined. The ethyl acetate was removed by concentration, and ethanol (7 mL) was used as solvent for recrystallization to obtain 2-(1-bromo-2-(phenylsulfonyl)ethyl)naphthalene (1.313 g, 3.5 mmol) with a yield of 70% (purity 99.0%).
[0066] 1 H NMR (600MHz, CDCl3) δ7.73(d,J=9.4Hz,2H),7.61(d,J=8.5Hz,1H),7.51(dd,J=26.6,8.4Hz,5H),7.31(dd,J=19.2,11.7 Hz,2H),7.14(t,J=7.9Hz,2H),5.56(dd,J=9.8,5.1Hz,1H),4.25(dd,J=14.8,9.8Hz,1H),4.15(dd,J=14.8,5.1Hz,1H).
[0067] Example 8: Preparation of 4-(1-bromo-2-(phenylsulfonyl)ethyl)-1,1'-biphenyl by solid phase chemical method using 4-vinylbiphenyl, sodium phenylsulfinate and copper bromide
[0068] The chemical reaction formula for preparing the compound 4-(1-bromo-2-(phenylsulfonyl)ethyl)-1,1'-biphenyl in this example is as follows:
[0069]
[0070] The specific preparation process is as follows:
[0071] Under air atmosphere, sodium phenylsulfinate (0.985 g, 6.0 mmol), copper bromide (2.680 g, 12.0 mmol), 4-vinylbiphenyl (0.901 g, 5.0 mmol) were weighed into a 10 mL ball mill (304 stainless steel material), and finally 1 304 stainless steel bead with a diameter of 1 cm (for ball milling) was added, and the ball mill was closed and covered. The ball mill was placed in a ball mill, and ball milling was performed 6 times according to the procedure of ball milling for 30 minutes / pause for 5 minutes and a frequency of 30 Hz for a total of 3 hours. The reaction was stopped, 10 ml of ethyl acetate was added to the ball mill to dissolve the product, and the product was filtered, and the ball mill and solid residue were washed with 10 ml of ethyl acetate, and the ethyl acetate filtrate was combined. The ethyl acetate was removed by concentration, and ethanol (7 mL) was used as a solvent for recrystallization to obtain 4-(1-bromo-2-(phenylsulfonyl)ethyl)-1,1'-biphenyl (1.365 g, 3.4 mmol) with a yield of 68% (purity 99.3%).
[0072] 1 H NMR(600MHz, CDCl3)δ7.68(t,J=8.8Hz,2H),7.49(dd,J=16.7,7.7Hz,3H),7.44–7.37(m,5H) ,7.33(dd,J=12.0,7.0Hz,2H),7.26(s,2H),5.36(t,J=7.0Hz,1H),3.95(s,1H),3.91(s,1H).
[0073] Example 9: Preparation of 2-(1-bromo-2-toluenesulfonylethyl)naphthalene by solid phase chemical method using 2-vinylnaphthalene, sodium p-tolylsulfinate and copper bromide
[0074] The chemical reaction formula for preparing the compound 2-(1-bromo-2-toluenesulfonylethyl)naphthalene in this example is as follows:
[0075]
[0076] The specific preparation process is as follows:
[0077] Under air atmosphere, sodium p-toluenesulfinate (1.069 g, 6.0 mmol), copper bromide (2.680 g, 12.0 mmol), 2-vinylnaphthalene (0.771 g, 5.0 mmol) were weighed into a 10 mL ball mill (304 stainless steel material), and 1 304 stainless steel bead with a diameter of 1 cm was added (to play a ball milling role), and the ball mill was closed and covered. The ball mill was placed in a ball mill, and ball milling was performed 6 times according to the procedure of ball milling for 30 minutes / pause for 5 minutes and a frequency of 30 Hz, for a total of 3 hours. Stop the reaction, add 10 ml of ethyl acetate to the ball mill to dissolve the product, filter, and then use 10 ml of ethyl acetate to wash the ball mill and solid residue, and combine the ethyl acetate filtrate. The ethyl acetate was removed by concentration, and ethanol (7 mL) was used as solvent for recrystallization to obtain 2-(1-bromo-2-toluenesulfonylethyl)naphthalene (1.265 g, 3.25 mmol) with a yield of 65% (purity 99.2%).
[0078] 1 H NMR (600MHz, CDCl3) δ7.82-7.67(m,2H),7.61(d,J=9.1Hz,2H),7.49(dd,J=6.2,3.2Hz,2H),7.38(d,J=8.2Hz,2H),7.26(s,1H) ,6.87(d,J=8.2Hz,2H),5.54(dd,J=10.0,4.8Hz,1H),4.24(dd,J=14.8,10.1Hz,1H),4.12(dd,J=14.8,4.8Hz,1H),2.15(s,3H).
[0079] Example 10: Preparation of 2-(1-bromo-2-((4-chlorophenyl)sulfonyl)ethyl)naphthalene by solid phase chemical method using 2-vinylnaphthalene, sodium p-chlorophenylsulfinate and copper bromide
[0080] The chemical reaction formula for preparing the compound 2-(1-bromo-2-((4-chlorophenyl)sulfonyl)ethyl)naphthalene in this example is as follows:
[0081]
[0082] The specific preparation process is as follows:
[0083] Under air atmosphere, sodium p-chlorophenylsulfinate (1.192 g, 6.0 mmol), copper bromide (2.680 g, 12.0 mmol), 2-vinylnaphthalene (0.771 g, 5.0 mmol) were weighed into a 10 mL ball mill (304 stainless steel material), and 1 304 stainless steel bead with a diameter of 1 cm (for ball milling) was added, and the ball mill was closed and covered. The ball mill was placed in a ball mill, and ball milling was performed 6 times according to the procedure of ball milling for 30 minutes / pause for 5 minutes and a frequency of 30 Hz for a total of 3 hours. The reaction was stopped, 10 ml of ethyl acetate was added to the ball mill to dissolve the product, and the product was filtered, and the ball mill and solid residue were washed with 10 ml of ethyl acetate, and the ethyl acetate filtrate was combined. The ethyl acetate was removed by concentration, and ethanol (7 mL) was used as solvent for recrystallization to obtain 2-(1-bromo-2-((4-chlorophenyl)sulfonyl)ethyl)naphthalene (1.229 g, 3.0 mmol) with a yield of 60% (purity 99.1%).
[0084] 1 H NMR (600MHz, CDCl3) δ7.78-7.71(m,2H),7.66(s,1H),7.60(d,J=8.6Hz,1H),7.54-7.48(m,3H),7.37(d,J=8.6Hz,2H ), 6.99 (d, J = 8.6Hz, 2H), 5.54 (dd, J = 10.1, 5.0Hz, 1H), 4.24 (dd, J = 14.9, 10.1Hz, 1H), 4.14 (dd, J = 14.9, 5.0Hz, 1H).
[0085] The above-mentioned embodiments only express the specific implementation methods of the present application, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the protection scope of the present application. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the technical solution concept of the present application, and these all belong to the protection scope of the present application.
[0086] This background section is provided to generally present the context of the invention, and the work of the presently named inventors, the work to the extent described in this background section, and aspects of this section that did not constitute prior art at the time of application are neither explicitly nor implicitly admitted to be prior art to the present invention.
Claims
1. A method for preparing (1-bromo-2-(arylsulfonyl)ethyl)arene by solid phase chemical method, characterized in that The following steps are involved: In an air atmosphere, add aromatic olefin, sodium aromatic sulfinate and copper bromide into a ball mill; close the ball mill, and perform ball milling reaction on the above substances for a certain period of time to obtain (1-bromo-2-(arylsulfonyl)ethyl)arene.
2. The method for preparing (1-bromo-2-(arylsulfonyl)ethyl)arene by solid phase chemical method according to claim 1, characterized in that: The molar ratio of the aromatic olefin, the sodium aromatic sulfinate and the copper bromide is 1:1.2-1.5:2.4-3.
0.
3. The method for preparing (1-bromo-2-(arylsulfonyl)ethyl)arene by solid phase chemical method according to claim 1, characterized in that: The molar ratio of the aromatic olefin, sodium aromatic sulfinate and copper bromide is 5:6:
12.
4. A method for preparing (1-bromo-2-(arylsulfonyl)ethyl)arene by solid phase chemical method as claimed in any one of claims 1 to 3, characterized in that: The ball mill is made of 304 stainless steel or zirconium oxide.
5. A method for preparing (1-bromo-2-(arylsulfonyl)ethyl)arene by solid phase chemical method as claimed in claim 4, characterized in that: The ball milling reaction time is 2 hours or more.
6. A method for preparing (1-bromo-2-(arylsulfonyl)ethyl)arene by solid phase chemical method as claimed in claim 5, characterized in that: The aromatic olefins include, but are not limited to, styrene, 4-tert-butylstyrene, 2-vinylnaphthalene, and 4-vinylbiphenyl.
7. A method for preparing (1-bromo-2-(arylsulfonyl)ethyl)arene by solid phase chemical method as claimed in claim 5, characterized in that: The sodium arylsulfinate includes but is not limited to sodium phenylsulfinate, sodium p-chlorophenylsulfinate, and sodium p-toluenesulfinate.
8. A method for preparing (1-bromo-2-(arylsulfonyl)ethyl)arene by solid phase chemical method as claimed in any one of claims 1, 2, 4 and 6, characterized in that: The method also includes a separation and purification step.
9. A method for preparing (1-bromo-2-(arylsulfonyl)ethyl)arene by solid phase chemical method as claimed in claim 8, characterized in that: The specific operation of the separation and purification step is: after the ball milling reaction is completed, the product is dissolved in ethyl acetate, filtered and the filter residue is removed to obtain an ethyl acetate solution containing (1-bromo-2-(arylsulfonyl)ethyl)arene; then the solvent is removed by concentration, and then ethanol is used for recrystallization and purification to finally obtain purified (1-bromo-2-(arylsulfonyl)ethyl)arene.
10. A method for preparing (1-bromo-2-(arylsulfonyl)ethyl)arene by solid phase chemical method as claimed in claim 9, characterized in that: The purity of the purified (1-bromo-2-(arylsulfonyl)ethyl)arene reaches 99.0% or more.