Preparation method of 2-(4-bromophenyl) norcamphane

Abstract

The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of 2-(4-bromophenyl) norcamphane. According to the invention, the proper catalyst is selected to promote the norbornene to be directly added with the bromobenzene Grignard reagent, so that the use of expensive raw materials is avoided, the reaction difficulty is reduced, and the reaction can be smoothly carried out, thereby effectively improving the reaction yield of the 2-phenyl norcamphane. According to the bromination reaction of the 2-phenyl norcamphane, proper catalysts and reaction conditions are selected, and the selectivity of para-products is improved, so that the product yield of the 2-(4-bromophenyl) norcamphane is improved.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and particularly relates to a method for preparing 2-(4-bromophenyl)norbornane. Background Art

[0002] 2-(4-Bromophenyl)norbornane is an important intermediate, mainly used in the preparation of bicycloheptylamine luminescent materials.

[0003] At present, there are relatively few studies on 2-(4-bromophenyl) norbornane. The preparation method of the intermediate 2-phenylnorbornane is mainly to react p-bromoiodobenzene with norbornene. The synthesis method uses DMF as solvent and potassium carbonate as acid-attaching agent, and needs to react at 150° C. for 96 hours. Among them, p-bromoiodobenzene is expensive and has a long reaction cycle, resulting in high product cost, which is not suitable for industrial production. 2-(4-bromophenyl) norbornane is synthesized by bromination of 2-phenylnorbornane. In the prior art, trifluoroacetic acid is used as solvent and bromine is used for bromination reaction at 50° C., and the yield is only 53%, which is low in yield and high in production cost, and cannot be industrialized. Summary of the invention

[0004] The object of the present invention is to provide a method for preparing 2-(4-bromophenyl)norbornane. The method provided by the present invention has high yield of 2-(4-bromophenyl)norbornane and low raw material cost, and is suitable for industrial production.

[0005] In order to achieve the above object, the present invention provides the following technical solutions:

[0006] The present invention provides a method for preparing 2-(4-bromophenyl)norbornane, comprising the following steps:

[0007] Mixing norbornene, phenylmagnesium bromide, a first organic solvent and a first catalyst for addition reaction to obtain 2-phenylnorbornene; the first catalyst comprises one or more of zirconocene dichloride, titanocene dichloride and hafnocene dichloride;

[0008] The 2-phenylnorbornane, a second organic solvent, a second catalyst and a bromination reagent are mixed to carry out a bromination reaction to obtain the 2-(4-bromophenyl)norbornane; the second catalyst comprises one or more of aluminum trichloride, ferric tribromide, aluminum tribromide, ferric chloride and sulfuric acid.

[0009] Preferably, the molar ratio of norbornene to phenylmagnesium bromide is 1:1-3.

[0010] Preferably, the amount of the first catalyst is 5-10% of norbornene.

[0011] Preferably, the mixing of norbornene, phenylmagnesium bromide, a first organic solvent and a first catalyst comprises:

[0012] After norbornene is dispersed in the first organic solvent, phenylmagnesium bromide and the first catalyst are added in sequence; the adding temperature is 0-50°C.

[0013] Preferably, the temperature of the addition reaction is 0 to 50° C. and the time is 15 to 20 hours.

[0014] Preferably, after the addition reaction, the obtained reaction system is subjected to post-treatment;

[0015] The post-treatment comprises: placing the reaction system in hydrochloric acid for hydrolysis, adding toluene for extraction and liquid separation to obtain an organic phase; washing the organic phase with water until it is neutral, and then concentrating and distilling.

[0016] Preferably, the brominating agent includes bromine, NBS or dibromohydantoin; and the molar ratio of the 2-phenylnorbornane to the brominating agent is 0.1:0.1-0.13.

[0017] Preferably, the mass of the second catalyst is 1 to 10% of the mass of 2-phenylnorbornane.

[0018] Preferably, the temperature of the bromination reaction is -10 to 30°C.

[0019] Preferably, after the bromination reaction, the obtained reaction system is further subjected to post-treatment;

[0020] The post-treatment comprises: quenching and separating the reaction system to obtain an organic phase; washing the organic phase with water until it is neutral, and then concentrating and purifying it through crystallization.

[0021] The invention provides a method for preparing 2-(4-bromophenyl)norbornane, comprising the following steps: mixing norbornene, phenylmagnesium bromide, a first organic solvent and a first catalyst, performing an addition reaction, and obtaining 2-phenylnorbornane; the first catalyst comprises one or more of dichloro zirconocene, dichloro titanocene and dichloro hafnocene; the 2-phenylnorbornane, a second organic solvent, a second catalyst and a bromination reagent are mixed, and a bromination reaction is performed to obtain the 2-(4-bromophenyl)norbornane; the second catalyst comprises one or more of aluminum chloride, ferric bromide, aluminum tribromide, ferric chloride and sulfuric acid. The invention promotes the direct addition of norbornene with a bromobenzene Grignard reagent by selecting a suitable catalyst, avoids the use of expensive raw materials, reduces the difficulty of the reaction, and enables the reaction to proceed smoothly, thereby effectively improving the reaction yield of 2-phenylnorbornane. The bromination reaction of 2-phenylnorbornane can improve the selectivity of the para-product by selecting a suitable catalyst and reaction conditions, thereby improving the product yield of 2-(4-bromophenyl)norbornane. DETAILED DESCRIPTION

[0022] The present invention provides a method for preparing 2-(4-bromophenyl)norbornane, comprising the following steps:

[0023] Mixing norbornene, phenylmagnesium bromide, a first organic solvent and a first catalyst for addition reaction to obtain 2-phenylnorbornene; the first catalyst comprises one or more of zirconocene dichloride, titanocene dichloride and hafnocene dichloride;

[0024] The 2-phenylnorbornane, a second organic solvent, a second catalyst and a bromination reagent are mixed to carry out a bromination reaction to obtain the 2-(4-bromophenyl)norbornane; the second catalyst comprises one or more of aluminum trichloride, ferric tribromide, aluminum tribromide, ferric chloride and sulfuric acid.

[0025] The invention mixes norbornene, phenylmagnesium bromide, a first organic solvent and a first catalyst, and performs an addition reaction to obtain 2-phenylnorbornene.

[0026] In the present invention, the phenylmagnesium bromide is preferably obtained by preparation, and the preparation preferably comprises the following steps: after mixing magnesium, tetrahydrofuran and iodine, adding bromobenzene in batches, and reacting under stirring to obtain the phenylmagnesium bromide.

[0027] In the present invention, the dosage ratio of magnesium to tetrahydrofuran is preferably 0.1-0.3 mol: 50 g; the dosage ratio of magnesium to iodine is preferably 0.1-0.3 mol: 0.001 g; the molar ratio of magnesium to bromobenzene is preferably 0.1-0.3: 0.1-0.3; the bromobenzene is preferably added in two times, the mass of the first added bromobenzene is 3-4% of the total mass of bromobenzene; the second addition of bromobenzene is preferably dropwise. In a specific embodiment of the present invention, the process of mixing raw materials is preferably: premixing magnesium and tetrahydrofuran, heating to the reaction temperature, and then adding iodine and bromobenzene.

[0028] In the present invention, the reaction temperature is preferably 30-50° C., and the reaction time is preferably 1-3 h; and the reaction is preferably carried out under stirring.

[0029] In the present invention, the molar ratio of norbornene to phenylmagnesium bromide is preferably 1:1-3, specifically 1:1, 1:1.2, 1:1.5, 1:2 or 1:3. In the present invention, the first organic solvent includes tetrahydrofuran or methyltetrahydrofuran; the amount ratio of norbornene to the first organic solvent is preferably 0.1 mol:20 g. In the present invention, the first catalyst includes one or more of dichloro zirconocene, dichloro titanocene and dichloro hafnocene, preferably dichloro zirconocene; the amount of the first catalyst is preferably 5-10% of norbornene.

[0030] In the present invention, the mixing of norbornene, phenylmagnesium bromide, a first organic solvent and a first catalyst preferably comprises: dispersing norbornene in a first organic solvent, and then sequentially adding phenylmagnesium bromide and the first catalyst; the adding temperature is preferably 0 to 50°C.

[0031] In the present invention, the temperature of the addition reaction is preferably 0 to 50° C., and the time is preferably 15 to 20 hours; and the addition reaction is preferably carried out under stirring.

[0032] After the addition reaction, the present invention also preferably includes post-treatment of the obtained reaction system; the post-treatment preferably includes: placing the reaction system in hydrochloric acid for hydrolysis, adding toluene for extraction and separation to obtain an organic phase; washing the organic phase with water until it is neutral, and then concentrating and distilling.

[0033] In the present invention, the concentration of the hydrochloric acid is preferably 10%; the mass ratio of norbornene to hydrochloric acid is preferably 9.4:36.5; and the mass ratio of hydrochloric acid to toluene is preferably 36.5:35.

[0034] In the present invention, the purity of the 2-phenylnorbornane is preferably 99.0% to 99.5%, and the yield is preferably 73.0% to 78.5%.

[0035] In the present invention, the synthetic route of the 2-phenylnorbornane is preferably:

[0036]

[0037] After obtaining the 2-phenylnorbornane, the present invention mixes the 2-phenylnorbornane, a second organic solvent, a second catalyst and a bromination reagent to carry out a bromination reaction to obtain the 2-(4-bromophenyl)norbornane.

[0038] In the present invention, the brominating agent preferably includes bromine, NBS or dibromohydantoin; the molar ratio of the 2-phenylnorbornane to the brominating agent is preferably 0.1:0.1-0.13.

[0039] In the present invention, the second organic solvent preferably includes dichloromethane, dichloroethane or chloroform; the amount ratio of the 2-phenylnorbornane to the second organic solvent is preferably 0.1 mol: 50 g. In the present invention, the second catalyst includes one or more of aluminum chloride, ferric bromide, aluminum tribromide, ferric chloride and sulfuric acid, preferably aluminum chloride; the mass of the second catalyst is preferably 1-10% of the mass of 2-phenylnorbornane.

[0040] In the present invention, the mixing process is preferably: premixing 2-phenylnorbornane, the second organic solvent and the second catalyst, and then dripping the bromination reagent. In the present invention, the bromination reaction begins after the bromination reagent is dripped. In the present invention, the temperature of the bromination reaction is preferably -10 to 30°C.

[0041] After the bromination reaction, the present invention also preferably includes post-treatment of the obtained reaction system; the post-treatment preferably includes: quenching and liquid separation of the reaction system to obtain an organic phase; after washing the organic phase with water until it is neutral, concentrating and crystallizing for purification. In the present invention, the quenching process is preferably: adding sodium sulfite and water to the reaction system for quenching; the mass ratio of the 2-phenylnorbornane, sodium sulfite and water is preferably 17.2:4-6:20-30.

[0042] In the present invention, the purity of the 2-(4-bromophenyl)norbornane is preferably 99.1 to 99.6%, and the yield is preferably 77 to 82%. In the present invention, the route of the bromination reaction is preferably:

[0043]

[0044] Unless otherwise specified, the materials and equipment used in the present invention are all commercially available products in the art.

[0045] The technical solutions in the present invention will be described clearly and completely below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0046] Example 1

[0047] Preparation of bromobenzene Grignard reagent: add 2.24g (0.1mol) magnesium and 50g tetrahydrofuran into a 250mL three-necked flask, heat to 45°C, add 0.001g iodine and 0.5g bromobenzene, after initiation, keep warm at 45°C and continue to drop 15.2g bromobenzene, add a total of 15.7g (0.1mol) bromobenzene, keep warm and stir for 1 hour after the addition is complete, to obtain bromobenzene Grignard reagent, i.e. phenylmagnesium bromide;

[0048] Addition reaction: add 9.4g (0.1mol) norbornene and 20g tetrahydrofuran to a 250mL three-necked flask, add the prepared bromobenzene Grignard reagent (0.1mol) dropwise at 30°C, then add 1.46g (0.005mol) zirconocene dichloride catalyst, and stir at 30°C for 15 hours after the addition to carry out the addition reaction; pour the obtained reaction system into 36.5g hydrochloric acid with a mass concentration of 10% for hydrolysis, extract with 35g toluene, separate the liquids, wash the organic phase with water until neutral, and obtain 12.9g (yield 75%) of 2-phenylnorbornene after concentration and distillation, with a purity of 99%;

[0049] Bromination reaction: 17.2 g (0.1 mol) of 2-phenylnorbornane, 50 g of dichloromethane and 0.0172 g of aluminum chloride were added to a 250 mL three-necked flask, and 16 g (0.1 mol) of bromine was added dropwise at 5 ° C. After the gas phase central control reaction was completed, 4 g of sodium sulfite and 20 g of water were added to the reaction system for quenching, the liquids were separated, the organic phase was washed with water to neutrality, and then concentrated and purified by crystallization to obtain 20.08 g (yield 80%) of 2-(4-bromophenyl)norbornane with a purity of 99.5%.

[0050] Example 2

[0051] Preparation of bromobenzene Grignard reagent: add 3.36g (0.15mol) magnesium and 70g tetrahydrofuran into a 250mL three-necked flask, heat to 35°C, add 0.001g iodine and 1g bromobenzene, after initiation, keep warm at 35°C and continue to drop 30.4g bromobenzene, add a total of 31.4g (0.2mol) bromobenzene, keep warm and stir for 1 hour after the addition is complete, to obtain bromobenzene Grignard reagent, i.e. phenylmagnesium bromide;

[0052] Addition reaction: add 9.4g (0.1mol) norbornene and 20g tetrahydrofuran to a 250mL three-necked flask, add the prepared bromobenzene Grignard reagent (0.15mol) dropwise at 35°C, then add 2.92g (0.010mol) zirconocene dichloride catalyst, and stir at 35°C for 18 hours after the addition to carry out the addition reaction; pour the obtained reaction system into 36.5g hydrochloric acid with a mass concentration of 10% for hydrolysis, extract with 35g toluene, separate the liquids, wash the organic phase with water until neutral, and obtain 12.73g (yield 74%) of 2-phenylnorbornene after concentration and distillation, with a purity of 99.1%;

[0053] Bromination reaction: 17.2 g (0.1 mol) of 2-phenylnorbornane, 50 g of dichloromethane and 0.0172 g of aluminum chloride were added to a 250 mL three-necked flask, and 19.2 g (0.12 mol) of bromine was added dropwise at 0 ° C. After the gas phase central control reaction was completed, 4.3 g of sodium sulfite and 20 g of water were added to the reaction system for quenching, the liquids were separated, the organic phase was washed with water to neutrality, and then concentrated and purified by crystallization to obtain 19.58 g (yield 78%) of 2-(4-bromophenyl)norbornane with a purity of 99.4%.

[0054] Example 3

[0055] Preparation of bromobenzene Grignard reagent: add 4.48g (0.2mol) magnesium and 100g tetrahydrofuran to a 250mL three-necked flask, heat to 50°C, add 0.001g iodine and 1g bromobenzene, after initiation, keep warm at 45°C and continue to drop 22.5g bromobenzene, add a total of 23.5g (0.15mol) bromobenzene, keep warm and stir for 2 hours after the addition is complete, to obtain bromobenzene Grignard reagent, i.e. phenylmagnesium bromide;

[0056] Addition reaction: add 9.4g (0.1mol) norbornene and 20g tetrahydrofuran to a 250mL three-necked flask, add the prepared bromobenzene Grignard reagent (0.15mol) dropwise at 50°C, then add 1.75g ​​(0.006mol) zirconocene dichloride catalyst, and after the addition, stir at 50°C for 19 hours for addition reaction; pour the obtained reaction system into 36.5g hydrochloric acid with a mass concentration of 10% for hydrolysis, extract with 35g toluene, separate the liquids, wash the organic phase with water until neutral, and obtain 12.55g (yield 73%) of 2-phenylnorbornene after concentration and distillation, with a purity of 99.3%;

[0057] Bromination reaction: 17.2 g (0.1 mol) of 2-phenylnorbornane, 50 g of dichloroethane and 0.034 g of ferric chloride were added to a 250 mL three-necked flask, and 17.6 g (0.11 mol) of bromine was added dropwise at 15 ° C. After the gas phase central control reaction was completed, 4.1 g of sodium sulfite and 25 g of water were added to the reaction system for quenching, the liquids were separated, the organic phase was washed with water to neutrality, and then concentrated and purified by crystallization to obtain 19.58 g (yield 78%) of 2-(4-bromophenyl)norbornane with a purity of 99.3%.

[0058] Example 4

[0059] Preparation of bromobenzene Grignard reagent: add 2.24g (0.1mol) magnesium and 50g methyltetrahydrofuran into a 250mL three-necked flask, heat to 40°C, add 0.001g iodine and 0.8g bromobenzene, after initiation, keep warm at 40°C and continue to drop 18.0g bromobenzene, add a total of 18.8g (0.12mol) bromobenzene, keep warm and stir for 3 hours after the addition is complete, to obtain bromobenzene Grignard reagent, i.e. phenylmagnesium bromide;

[0060] Addition reaction: add 9.4g (0.1mol) norbornene and 20g methyltetrahydrofuran to a 250mL three-necked flask, add the prepared bromobenzene Grignard reagent (0.1mol) dropwise at 20°C, and then add 2.04g (0.007mol) zirconocene dichloride catalyst, and after the addition, stir at 20°C for 20 hours for addition reaction; pour the obtained reaction system into 36.5g hydrochloric acid with a mass concentration of 10% for hydrolysis, extract with 35g toluene, separate the liquids, wash the organic phase with water until neutral, and obtain 12.81g (yield 74.5%) of 2-phenylnorbornene after concentration and distillation, with a purity of 99.25%;

[0061] Bromination reaction: 17.2 g (0.1 mol) of 2-phenylnorbornane, 50 g of chloroform and 0.0516 g of aluminum chloride were added to a 250 mL three-necked flask, and 26.7 g (0.15 mol) of NBS was added dropwise at 15 ° C. After the gas phase central control reaction was completed, 5 g of sodium sulfite and 20 g of water were added to the reaction system for quenching, the liquids were separated, the organic phase was washed with water to neutrality, and then concentrated and purified by crystallization to obtain 19.7 g (yield 78.5%) of 2-(4-bromophenyl)norbornane with a purity of 99.33%.

[0062] Example 5

[0063] Preparation of bromobenzene Grignard reagent: add 2.88g (0.12mol) magnesium and 60g tetrahydrofuran into a 250mL three-necked flask, heat to 45°C, add 0.001g iodine and 1g bromobenzene, after initiation, keep warm at 45°C and continue to drop 25.7g bromobenzene, add a total of 26.7g (0.17mol) bromobenzene, keep warm and stir for 1.5 hours after the addition is complete, to obtain bromobenzene Grignard reagent, i.e. phenylmagnesium bromide;

[0064] Addition reaction: add 9.4g (0.1mol) norbornene and 20g tetrahydrofuran to a 250mL three-necked flask, add the prepared bromobenzene Grignard reagent (0.12mol) dropwise at 30°C, then add 2.92g (0.01mol) zirconocene dichloride catalyst, and after the addition, stir at 30°C for 16 hours for addition reaction; pour the obtained reaction system into 36.5g hydrochloric acid with a mass concentration of 10% for hydrolysis, extract with 35g toluene, separate the liquids, wash the organic phase with water until neutral, and obtain 13.07g (yield 76%) of 2-phenylnorbornene after concentration and distillation, with a purity of 99.15%;

[0065] Bromination reaction: 17.2 g (0.1 mol) of 2-phenylnorbornane, 50 g of dichloromethane and 0.0172 g of aluminum chloride were added to a 250 mL three-necked flask, and 17.6 g (0.11 mol) of bromine was added dropwise at -5 °C. After the gas phase central control reaction was completed, 4.4 g of sodium sulfite and 20 g of water were added to the reaction system for quenching, the liquids were separated, the organic phase was washed with water to neutrality, and then concentrated and purified by crystallization to obtain 19.33 g (yield 77.8%) of 2-(4-bromophenyl)norbornane with a purity of 99.1%.

[0066] Although the above embodiment describes the present invention in detail, it is only a part of the embodiments of the present invention, not all of the embodiments. Other embodiments can be obtained based on this embodiment without creativity, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A method for preparing 2-(4-bromophenyl)norbornane, characterized in that: The following steps are involved: Mixing norbornene, phenylmagnesium bromide, a first organic solvent and a first catalyst for addition reaction to obtain 2-phenylnorbornene; the first catalyst comprises one or more of zirconocene dichloride, titanocene dichloride and hafnocene dichloride; The 2-phenylnorbornane, a second organic solvent, a second catalyst and a bromination reagent are mixed to carry out a bromination reaction to obtain the 2-(4-bromophenyl)norbornane; the second catalyst comprises one or more of aluminum trichloride, ferric tribromide, aluminum tribromide, ferric chloride and sulfuric acid.

2. The preparation method according to claim 1, characterized in that: The molar ratio of norbornene to phenylmagnesium bromide is 1:1-3.

3. The preparation method according to claim 2, characterized in that: The amount of the first catalyst is 5-10% of norbornene.

4. The preparation method according to claim 1, characterized in that: The mixing of norbornene, phenylmagnesium bromide, a first organic solvent and a first catalyst comprises: After norbornene is dispersed in the first organic solvent, phenylmagnesium bromide and the first catalyst are added in sequence; the adding temperature is 0-50°C.

5. The preparation method according to claim 1 or 4, characterized in that: The temperature of the addition reaction is 0-50° C. and the time is 15-20 hours.

6. The preparation method according to claim 5, characterized in that: After the addition reaction, the obtained reaction system is subjected to post-treatment; The post-treatment comprises: placing the reaction system in hydrochloric acid for hydrolysis, adding toluene for extraction and liquid separation to obtain an organic phase; washing the organic phase with water until it is neutral, and then concentrating and distilling.

7. The preparation method according to claim 1, characterized in that: The bromination reagent comprises bromine, NBS or dibromohydantoin; the molar ratio of the 2-phenylnorbornane to the bromination reagent is 0.1:0.1-0.

13.

8. The preparation method according to claim 7, characterized in that: The mass of the second catalyst is 1-10% of the mass of 2-phenylnorbornane.

9. The preparation method according to claim 1 or 8, characterized in that: The temperature of the bromination reaction is -10 to 30°C.

10. The preparation method according to claim 9, characterized in that: After the bromination reaction, the obtained reaction system is subjected to post-treatment; The post-treatment comprises: quenching and separating the reaction system to obtain an organic phase; washing the organic phase with water until it is neutral, and then concentrating and purifying it through crystallization.

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