Preparation method of 9, 9-bis [3-substituted-4-(2-hydroxyethoxy) phenyl] fluorene

Abstract

The invention discloses a preparation method of 9, 9-bis [3-substituted-4-(2-hydroxyethoxy) phenyl] fluorene, which belongs to the technical field of chemical synthesis of organic compounds, and is characterized by comprising the following steps: in the presence of an organic solvent, reacting 9, 9-bis (3-R-4-hydroxyphenyl) fluorene with 2-halogenated ethanol in an alkaline medium to prepare 9, 9-bis [3-substituted-4-(2-hydroxyethoxy) phenyl] fluorene; the invention relates to a 9, 9-bis [3-R-4-(2-hydroxyethoxy) phenyl] fluorene target product. Compared with the prior art, the method has the advantages of cheap and easily available raw materials, good reaction yield, high purity, mild reaction conditions and simple operation, and is suitable for industrial production.

Description

Technical Field

[0001] The present invention relates to a chemical synthesis process of organic compounds, and particularly to a preparation method of 9,9-bis[3-substituted-4-(2-hydroxyethoxy)phenyl]fluorene. Background Art

[0002] Bisphenol-structured compounds are an important class of organic chemical intermediates and can be widely used in the preparation of functional polymer materials through condensation reactions, such as epoxy resins, polycarbonates, polyethers, polyacrylates, and polyimides. Due to their excellent adhesion, transparency, impact resistance, heat resistance, high stability, and mechanical strength, these polymer materials exhibit extremely high application value in many fields such as coatings, adhesives, optical displays, machinery manufacturing, and construction. These high-molecular materials have become indispensable key materials, especially in fields such as automotive manufacturing, aerospace, missile warheads, chip packaging, display manufacturing, high-end precision optical lenses, optical imaging, and electronic appliances.

[0003] However, since the bisphenol A residues in products prepared from traditional bisphenol A (BPA) pose potential hazards to human health, which may lead to endocrine disorders, precocious puberty in children, and threaten the healthy development of fetuses and children. Therefore, most countries in the world have prohibited the use of products made of bisphenol A, such as baby bottles, children's sippy cups, beverage bottles, mineral water bottles, medical devices, and food packaging.

[0004] To solve this problem, researchers have developed a method that uses phenoxyethanol and 9-fluorenone as raw materials to generate a bisphenylfluorene-structured compound (BPEF) (III) with a Cardo molecular skeleton through a condensation reaction (Scheme II). Such compounds not only have similar physical and chemical properties to traditional bisphenol A products but also avoid the toxicity problem of residual bisphenol A. Therefore, the corresponding products can be safely used in the production of healthy and safe products such as baby bottles, sippy cups, and medical devices.

[0005]

[0006] Introducing a non-coplanar Cardo unique molecular backbone structure into polymer materials can effectively prevent the close packing of molecular chains, reduce the intermolecular interaction force, and thus improve the solubility, fluidity, heat resistance, formability, safety and other properties of the prepared polymer materials. BPEF (9,9-bis[4-(2-hydroxyethoxy)phenyl]fluorene) is a typical Cardo structure monomer compound, which can be obtained by the condensation reaction of 9-fluorenone and 2-phenoxyethanol under the action of a strong acid catalyst. The corresponding synthesis methods have been publicly reported in the literature and patents, such as the literature published in journals (Synth. Commun., 2007, 37: 4407-4413 and Green Chem., 2000, 2, 157-160), and the publicly disclosed patent documents (CN112142574A, Japanese Patent Laid-Open No. 10-45656, Japanese Patent Laid-Open No. 2009-256342, and CN104144904A, etc.).

[0007] However, due to the relatively high crystallinity of the polymer materials prepared from BPEF monomers, their application scope is limited. By introducing other groups (such as non-polar alkyl or aryl groups) onto the aromatic ring of BPEF, the intermolecular interaction force can be further reduced, the steric hindrance within the molecule can be increased, thereby reducing the crystallinity of the material, and at the same time reducing the glass transition temperature of the material, achieving the effects of improving the flexibility, elasticity, transparency, adhesion, impact resistance, fluidity, dielectric properties, heat and humidity resistance, chemical corrosion resistance of the material, and enhancing the refractive index. In addition, this modification can also adjust the electrical properties of the material (such as conductivity and dielectric constant) to ensure that the material can maintain excellent mechanical properties in different temperature environments.

[0008]

[0009] Since the phenolic hydroxyl group (O-H) in bisphenol fluorene compounds is relatively acidic and easily oxidized and deteriorated (Bordwell and Zhang Xianman, Acc. Chem. Res, 1993, 26, 510-517), products with a more stable alcohol hydroxyl group structure are usually obtained by converting the phenolic hydroxyl group. There have been patent reports on the method of converting the phenolic hydroxyl group of 9,9-bis(3-phenyl-4-hydroxyphenyl)fluorene into an alcohol hydroxyl group (Japanese Patent Laid-Open No. 2001-122828), that is, reacting with ethylene oxide under alkaline conditions. However, this method has more by-products in the reaction of phenoxyethanol, and the purity of the target product is low. Another method is to prepare it by reacting with ethylene carbonate under alkaline conditions, but it requires catalysts such as triphenylphosphine, and at the same time has poor atom economy, slow reaction rate, long reaction time, and unsatisfactory economic efficiency (CN03965028A).

[0010] After searching the publicly reported literature and patent databases at home and abroad, no relevant literature or patent reports have been found on the preparation of 9,9-bis[3-R-4-(2-hydroxyethoxy)phenyl]fluorene from the intermediate 9,9-bis(3-R-4-hydroxyphenyl)fluorene and 2-haloethanol. Through a large number of experiments, we found that in an alkaline medium, 9,9-bis[3-R-4-(2-hydroxyethoxy)phenyl]fluorene can be efficiently prepared by the reaction of 2-haloethanol and 9,9-bis(3-R-4-hydroxyphenyl)fluorene, and 2-haloethanol can be prepared by the reaction of ethylene oxide with hydrogen halide. In the prior art, the reaction of ethylene oxide and phenylbisphenol fluorene under alkaline conditions is prone to produce by-products (such as phenyl monoether fluorene and phenyl polyether fluorene, CN113548947 B). In view of the above problems, the present invention provides a simple and efficient method for synthesizing 9,9-bis[3-R-4-(2-hydroxyethoxy)phenyl]fluorene, which has important industrial application value. Summary of the Invention

[0011] The object of the present invention is to provide a method for preparing 9,9-bis[3-substituted-4-(2-hydroxyethoxy)phenyl]fluorene with high purity, high yield, safety and efficiency of the reaction product.

[0012] To achieve the above object, the technical scheme adopted by the present invention is as follows:

[0013] A method for preparing 9,9-bis[3-substituted-4-(2-hydroxyethoxy)phenyl]fluorene, characterized by comprising the following steps: in the presence of an organic solvent, 9,9-bis(3-R-4-hydroxyphenyl)fluorene (I) and 2-haloethanol react in an alkaline medium to prepare the target product 9,9-bis[3-R-4-(2-hydroxyethoxy)phenyl]fluorene (II).

[0014]

[0015] In the reaction formula:

[0016] X is a halogen, preferably Br, Cl or I;

[0017] R is an alkyl group, a phenyl group or a substituted alkyl group, a substituted phenyl group.

[0018] Further settings are as follows:

[0019] The 2-haloethanol is selected from any one of 2-chloroethanol, 2-bromoethanol, or 2-iodoethanol. 2-Haloethanol can be prepared by the reaction of ethylene oxide with the corresponding hydrohalic acid.

[0020]

[0021] The molar ratio of the reaction of the reaction intermediate 9,9-bis(3-R-4-hydroxyphenyl)fluorene (I) and 2-haloethanol is 1:1 to 1:10, and the preferred molar ratio is 1:2 to 1:3.

[0022] The basic medium is selected from any one or more of the following: potassium carbonate, sodium carbonate, potassium hydroxide, sodium hydroxide, lithium hydroxide, etc. The preferred basic medium is sodium hydroxide.

[0023] The organic solvent is selected from one or more of the following: methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, sec-butanol, tert-butanol, ethylene glycol, acetone, acetonitrile, N,N-dimethylformamide (DMF), N,N-dimethylacetamide, dimethyl sulfoxide (DMSO), N-methylpyrrolidone, etc. The preferred reaction solvent is N,N-dimethylformamide (DMF). The amount of the solvent is 2 to 15 times the mass of 9,9-bis(3-R-4-hydroxyphenyl)fluorene, and preferably 3 to 5 times.

[0024] A preparation method of 9,9-bis[3-substituted-4-(2-hydroxyethoxy)phenyl]fluorene, which is characterized by comprising the following steps:

[0025] (1) Intermediate preparation: In an organic solvent protected by nitrogen or other inert gases, using 9-fluorenone as a reaction raw material, under the synergistic action of a strong acid catalyst and a mercapto compound co-catalyst, a bisphenol compound intermediate 9,9-bis(3-R-4-hydroxyphenyl)fluorene (I) containing a Cardo ring skeleton structure is prepared by a condensation reaction;

[0026] (2) Target compound synthesis: The reaction intermediate prepared in step (1) is reacted with 2-haloethanol under basic conditions to prepare the target compound 9,9-bis[3-R-4-(2-hydroxyethoxy)phenyl]fluorene (II).

[0027] The chemical reaction equation involved in the present invention is as follows:

[0028]

[0029] In the step (1): The organic solvent is selected from one or more of toluene, fluorobenzene, chlorobenzene, o-dichlorobenzene, or 2-substituted phenol, and preferably 2-substituted phenol; the strong acid reagent is selected from one or more of concentrated sulfuric acid, methanesulfonic acid, p-toluenesulfonic acid, concentrated hydrochloric acid; the co-catalyst is β-mercaptopropionic acid or other mercapto compounds.

[0030] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0031] The raw materials are cheap and easily available, the reaction yield is good, the purity is high, the reaction conditions are mild, the operation is simple, and it is suitable for industrial production. Using 2-haloethanol as the etherification reagent avoids the problems of many by-products and low purity in the traditional method. The reaction steps are concise, and it has many advantages such as easy operation, good product purity, high yield, not demanding on equipment, and being suitable for large-scale industrial production. By introducing the Cardo ring skeleton structure, the chemical stability, heat resistance, and optical properties of the target product are significantly improved. The method provided by the present invention provides an efficient, economical, and environmentally friendly synthetic route for preparing high-performance bisphenol fluorene compounds and has broad application prospects.

[0032] The above content of the present invention will be further described in detail through the specific embodiments of the examples below, but it is not limited to the following examples. Under the above technical idea of the present invention, various substitutions or changes made according to the common general knowledge and conventional means in the art should be included within the protection scope of the present invention.

[0033] The process disclosed by the present invention will be further described below in conjunction with the accompanying drawings and specific embodiments. Description of the Drawings

[0034] Figure 1 HNMR spectrum of 9,9-bis[3-phenyl-4-(2-hydroxyethoxy)phenyl]fluorene prepared by the present invention. 1 HNMR spectrum.

[0035] Figure 2 High-resolution mass spectrum (HRMS) spectrum of 9,9-bis[3-phenyl-4-(2-hydroxyethoxy)phenyl]fluorene prepared by the present invention.

[0036] Figure 3 HNMR spectrum of 9,9-bis[3-methyl-4-(2-hydroxyethoxy)phenyl]fluorene prepared by the present invention. 1 HNMR spectrum. Specific Embodiments

[0037] In the following examples, 9,9-bis(3-methyl-4-hydroxy)phenylfluorene and 9,9-bis(3-phenyl-4-hydroxy)phenylfluorene intermediates react with 2-haloethanol under alkaline conditions to prepare the target products of 9,9-bis[3-methyl-4-(2-hydroxyethoxy)phenyl]fluorene and 9,9-bis[3-phenyl-4-(2-hydroxyethoxy)phenyl]fluorene respectively.

[0038] Example 1

[0039] Add 13.0 g of sodium carbonate and 200 mL of DMF to a 500 mL three-necked flask. While stirring in an ice-water bath, add 60.0 g of the 9,9-bis(3-phenyl-4-hydroxyphenyl)fluorene intermediate. After the organic matter has dissolved, add 24.0 g of 2-chloroethanol dropwise. After the addition is complete, raise the temperature to about 50 °C and react for 6 hours. After the reaction is complete, add 200 g of toluene, stir and then let stand. Separate the organic phase. Extract the aqueous phase twice with 50 g of toluene each time. Combine the organic phases and wash them twice with water. Cool the organic phase to crystallize, filter, rinse, and dry to obtain 65.6 g of 9,9-bis[3-phenyl-4-(2-hydroxyethoxy)phenyl]fluorene, with a yield of 93.0%.

[0040] Product confirmation: The 1 HNMR spectrum of the Figure 1 ) is consistent with the chemical structure of 9,9-bis[3-phenyl-4-(2-hydroxyethoxy)phenyl]fluorene. The high-resolution mass spectrum of the reaction product shows that the molecular weight (m / e) of its positive ion radical is 591.2490( Figure 2 ), which is consistent with that of 9,9-bis[3-phenyl-4-(2-hydroxyethoxy)phenyl]fluorene (C 41 H 34 O 4 Exact molecular weight: 590.25).

[0041]

[0042] Example 2

[0043] Add 13.0 g of sodium carbonate and 200 mL of DMF to a 500 mL three-necked flask. While stirring in an ice-water bath, add 45.2 g of the 9,9-bis(3-methyl-4-hydroxyphenyl)fluorene intermediate. After the organic matter has dissolved, add 24.0 g of 2-chloroethanol dropwise. After the addition is complete, raise the temperature to about 50 °C and react for 6 hours. After the reaction is complete, add 200 g of toluene, stir and then let stand. Separate the organic phase. Extract the aqueous phase twice with 50 g of toluene each time. Combine the organic phases and wash them twice with water. Cool the organic phase to crystallize, filter, rinse, and dry to obtain 50.6 g of 9,9-bis[3-methyl-4-(2-hydroxyethoxy)phenyl]fluorene, with a yield of 91.0%.

[0044] Product confirmation: The 1 HNMR spectrum of the Figure 3 ) is consistent with the chemical structure of 9,9-bis[3-methyl-4-(2-hydroxyethoxy)phenyl]fluorene.

[0045] Example 3

[0046] Add 6.7 g of sodium carbonate and 100 mL of DMF to a 250 mL three-necked flask. While stirring in an ice-water bath, add 30.2 g of 9,9-bis(3-phenyl-4-hydroxyphenyl)fluorene intermediate. After the organic matter is dissolved, add 18.8 g of 2-bromoethanol dropwise. After the addition is complete, raise the temperature to about 50 °C and react for 5 hours. After the reaction is completed, add 100 g of toluene, stir and then let stand. Separate the organic phase. Extract the aqueous phase with 40 g of toluene twice. Combine the organic phases and wash them with water twice. Cool the organic phase to crystallize, filter, rinse, and dry to obtain 26.6 g of 9,9-bis[3-phenyl-4-(2-hydroxyethoxy)phenyl]fluorene, with a yield of 95.0%.

[0047] Example 4

[0048] Add 6.7 g of sodium carbonate and 100 mL of DMF to a 250 mL three-necked flask. While stirring in an ice-water bath, add 22.7 g of 9,9-bis(3-methyl-4-hydroxyphenyl)fluorene intermediate. After the organic matter is dissolved, add 18.8 g of 2-bromoethanol dropwise. After the addition is complete, raise the temperature to about 50 °C and react for 6 hours. After the reaction is completed, add 100 g of toluene, stir and then let stand. Separate the organic phase. Extract the aqueous phase with 40 g of toluene twice. Combine the organic phases and wash them with water twice. Cool the organic phase to crystallize, filter, rinse, and dry to obtain 25.5 g of 9,9-bis[3-phenyl-4-(2-hydroxyethoxy)phenyl]fluorene, with a yield of 91.0%.

[0049] Example 5

[0050] Add 13.0 g of sodium carbonate and 200 mL of DMF to a 500 mL three-necked flask. While stirring in an ice-water bath, add 60.0 g of 9,9-bis(3-phenyl-4-hydroxyphenyl)fluorene intermediate. After the organic matter is dissolved, add 24.0 g of 2-chloroethanol dropwise. After the addition is complete, raise the temperature to about 80 °C and react for 5 hours. After the reaction is completed, add 200 g of toluene, stir and then let stand. Separate the organic phase. Extract the aqueous phase with 50 g of toluene twice. Combine the organic phases and wash them with water twice. Cool the organic phase to crystallize, filter, rinse, and dry to obtain 64.8 g of 9,9-bis[3-phenyl-4-(2-hydroxyethoxy)phenyl]fluorene, with a yield of 92.0%.

[0051] Example 6

[0052] Add 13.0 g of sodium carbonate and 200 mL of DMF to a 500 mL three-necked flask. While stirring in an ice-water bath, add 45.2 g of the 9,9-bis(3-methyl-4-hydroxyphenyl)fluorene intermediate. After the organic matter has dissolved, add dropwise 24.0 g of 2-chloroethanol. After the addition is complete, raise the temperature to about 80 °C and react for 5 hours. After the reaction is complete, add 200 g of toluene, stir and then let stand. Separate the organic phase. Extract the aqueous phase twice with 50 g of toluene each time. Combine the organic phases and wash twice with water. Cool the organic phase to crystallize, filter, rinse, and dry to obtain 51.7 g of 9,9-bis[3-methyl-4-(2-hydroxyethoxy)phenyl]fluorene, with a yield of 92.8%.

[0053] Example 7

[0054] Add 8.7 g of potassium carbonate and 100 mL of DMSO to a 250 mL three-necked flask. While stirring in an ice-water bath, add 30.2 g of the 9,9-bis(3-phenyl-4-hydroxyphenyl)fluorene intermediate. After the organic matter has dissolved, add dropwise 12.1 g of 2-chloroethanol. After the addition is complete, raise the temperature to about 60 °C and react for 5 hours. After the reaction is complete, add 100 g of toluene, stir and then let stand. Separate the organic phase. Extract the aqueous phase twice with 40 g of toluene each time. Combine the organic phases and wash twice with water. Cool the organic phase to crystallize, filter, rinse, and dry to obtain 33.3 g of 9,9-bis[3-phenyl-4-(2-hydroxyethoxy)phenyl]fluorene, with a yield of 93.7%.

[0055] Example 8

[0056] Add 8.7 g of potassium carbonate and 100 mL of DMSO to a 250 mL three-necked flask. While stirring in an ice-water bath, add 30.1 g of the 9,9-bis(3-methyl-4-hydroxyphenyl)fluorene intermediate. After the organic matter has dissolved, add dropwise 12.1 g of 2-chloroethanol. After the addition is complete, raise the temperature to about 60 °C and react for 5 hours. After the reaction is complete, add 100 g of toluene, stir and then let stand. Separate the organic phase. Extract the aqueous phase twice with 40 g of toluene each time. Combine the organic phases and wash twice with water. Cool the organic phase to crystallize, filter, rinse, and dry to obtain 25.3 g of 9,9-bis[3-methyl-4-(2-hydroxyethoxy)phenyl]fluorene, with a yield of 90.2%.

Claims

1. A method for preparing 9,9-bis[3-substituted-4-(2-hydroxyethoxy)phenyl]fluorene, characterized in that: The method comprises the following steps: in the presence of an organic solvent, 9,9-bis(3-R-4-hydroxyphenyl)fluorene (I) and 2-halogenated ethanol react in an alkaline medium to prepare 9,9-bis[3-R-4-(2-hydroxyethoxy)phenyl]fluorene (II); Where: X is a halogen, and R is an alkyl group, a phenyl group or a substitution thereof.

2. The method for preparing 9,9-bis[3-substituted-4-(2-hydroxyethoxy)phenyl]fluorene according to claim 1, characterized in that: The 2-haloethanol is selected from any one of 2-chloroethanol, 2-bromoethanol, or 2-iodoethanol.

3. The method for preparing 9,9-bis[3-substituted-4-(2-hydroxyethoxy)phenyl]fluorene according to claim 1, characterized in that: The molar ratio of the reaction intermediate 9,9-bis(3-R-4-hydroxyphenyl)fluorene (I) and 2-halogenated ethanol is 1:1 to 1:

10.

4. The method for preparing 9,9-bis[3-substituted-4-(2-hydroxyethoxy)phenyl]fluorene according to claim 3, characterized in that: The molar ratio of the reaction intermediate 9,9-bis(3-R-4-hydroxyphenyl)fluorene (I) and 2-halogenated ethanol is 1:2-1:

3.

5. The method for preparing 9,9-bis[3-substituted-4-(2-hydroxyethoxy)phenyl]fluorene according to claim 1, characterized in that: The alkaline medium is selected from any one or more of the following: potassium carbonate, sodium carbonate, potassium hydroxide, sodium hydroxide, lithium hydroxide, etc.

6. The method for preparing 9,9-bis[3-substituted-4-(2-hydroxyethoxy)phenyl]fluorene according to claim 5, characterized in that: The alkaline medium is sodium hydroxide.

7. The method for preparing 9,9-bis[3-substituted-4-(2-hydroxyethoxy)phenyl]fluorene according to claim 1, characterized in that: The organic solvent is selected from one or more of the following: methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, sec-butanol, tert-butanol, ethylene glycol, acetone, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, N-methylpyrrolidine, and the amount of the organic solvent is 2 to 15 times the mass of 9,9-bis(3-R-4-hydroxyphenyl)fluorene.

8. The method for preparing 9,9-bis[3-substituted-4-(2-hydroxyethoxy)phenyl]fluorene according to claim 7, characterized in that: The reaction solvent is N,N-dimethylformamide, and the amount of the organic solvent is 3 to 5 times the mass of 9,9-bis(3-R-4-hydroxyphenyl)fluorene.

9. The method for preparing 9,9-bis[3-substituted-4-(2-hydroxyethoxy)phenyl]fluorene according to claim 1, characterized in that: The steps include: (1) Preparation of intermediates: In an organic solvent protected by nitrogen or other inert gases, 9-fluorenone is used as a reaction raw material, and under the synergistic effect of a strong acid catalyst and a thiol compound co-catalyst, a bisphenol compound intermediate 9,9-bis(3-R-4-hydroxyphenyl)fluorene (I) containing a cardo ring skeleton structure is prepared by condensation reaction; (2) Synthesis of target compound: The reaction intermediate prepared in step (1) is reacted with 2-haloethanol under alkaline conditions to prepare the target compound 9,9-bis[3-R-4-(2-hydroxyethoxy)phenyl]fluorene (II).

10. The method for preparing 9,9-bis[3-substituted-4-(2-hydroxyethoxy)phenyl]fluorene according to claim 9, characterized in that: In step (1), the organic solvent is selected from one or more of toluene, fluorobenzene, chlorobenzene, o-dichlorobenzene, or 2-substituted phenol; the strong acidic reagent is selected from one or more of concentrated sulfuric acid, methanesulfonic acid, p-toluenesulfonic acid, and concentrated hydrochloric acid; and the co-catalyst is β-mercaptopropionic acid or other thiol compounds.

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