A method for synthesizing 5-(arylpropyl)furoic acid compounds

Abstract

The application discloses a synthesis method of 5-(arylpropyl) furanic acid compounds, under a nitrogen atmosphere, 5-(acetyloxymethyl) furan-2-carboxylic acid ethyl ester, an initiator, a Lewis base-borane, a mercaptan, an additive and an olefin are added into a solvent 1, and a reaction is carried out under stirring and heating to obtain 5-(arylpropyl) furanic acid ethyl ester compounds; the obtained 5-(arylpropyl) furanic acid ethyl ester compounds and a base are added into a solvent 2, and a reaction is carried out under stirring and heating; after the reaction is completed, organic phase impurities are removed by extraction, then the pH value of the aqueous solution is adjusted, dichloromethane is used for extraction again, and the obtained organic phase is concentrated and collected; a deprotection reagent is added into the concentrated product to carry out deprotection, and a target product is obtained. The 5-(arylpropyl) furanic acid compound is a new type of furan-based polymeric monomer, a polymer is prepared by using the monomer, and then the research and development of a new type of bio-based polymer are realized.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of organic synthesis, and particularly relates to a synthesis method of 5-(arylpropyl) furan acid compounds. BACKGROUND

[0002] Polyamides and polyesters are high molecular materials containing repeating amide groups and ester groups in the molecule. These two types of materials are widely used in the fields of automobile industry, textile industry, electrical industry, medical industry, etc. In recent years, with the continuous development of society and the continuous progress of technology, the demand for various functional polyamides and polyesters is increasing. Therefore, developing new methods to realize the development of new functional polyamides and polyesters is an important direction of synthetic chemistry and polymer chemistry research.

[0003] Biological platform molecules have the advantages of environmental friendliness and wide source. In recent years, synthetic workers have used chemical synthesis methods to modify biological platform molecules into polymer monomers with diverse structures, and thus realized the synthesis of various functional polymers. These research results have promoted the process of replacing traditional petrochemical raw materials with biological-based materials. For example, fructose and glucose can be modified into furandicarboxylic acid dimethyl ester or furandicarboxylic acid, and then further polycondensed with ethylene glycol to synthesize polyethylene glycol 2,5-furandicarboxylate (PEF). This type of polymer exhibits the advantages of biodegradability, excellent barrier property, and high mechanical strength (Zhou Q, Wang H N, Shi Y F, et al. Research Progress of Bio-based Polyester PEF [J]. Engineering Plastics Application, 2023, 51(01): 139-145.). In addition, furandicarboxylic acid can be polycondensed with various types of diamines to synthesize various types of furandicarboxylic acid polyamide materials. These polymers can be applied in the fields of membrane separation and heat-resistant materials (Li Z H, Yang X Q, Su K M, et al. Preparation and Properties of Environmentally Friendly Furanyl Polyamide Materials [J]. Tianjin University of Technology Journal, 2022, 41(04): 1-7.). The polymerization monomers of the above-mentioned bio-based polyesters and polyamides are furandicarboxylic acid. Although this compound exhibits wide application value, the types of bio-based monomers are far fewer than those derived from petrochemical raw materials, and the application potential of bio-based materials has not been fully developed. Therefore, it is still a long-term goal in this field to develop new bio-based polymerization monomers from readily available biological platform molecules through efficient synthesis methods.

[0004]

[0005] 5-hydroxymethylfurfuralic acid is an intermediate for synthesizing furandicarboxylic acid, which contains a carboxyl and a hydroxyl functional group. Developing an efficient method to realize the dehydroxy functionalization of 5-hydroxymethylfurfuralic acid and introduce amino and hydroxyl functional groups on the side chain of furan methylene is an effective way to transform it into various biobased polymer monomers, which is conducive to realizing various biobased polymers. In addition, the development of the method can also complete the high value of the biological platform molecule.

[0006] SUMMARY

[0007] The purpose of the present application is to provide a synthesis method of 5- (arylpropyl) furanic acid compounds to overcome the above-mentioned defects existing in the prior art.

[0008] The synthesis method of 5- (arylpropyl) furanic acid compounds of the present application comprises the following steps:

[0009] Step 1: under a nitrogen atmosphere, 5- (acetyloxymethyl) furan-2-carboxylic acid ethyl ester, initiator, Lewis base-borane, thiol, additive and olefin are added into solvent 1, heated and reacted under stirring, the reaction endpoint is determined by thin layer chromatography, then petroleum ether / ethyl acetate is mixed as eluent at a volume ratio of 50:1, and is separated by silica gel column to obtain 5- (arylpropyl) furanic acid ethyl ester compounds.

[0010] In step 1, the initiator is di-tert-butyl peroxide (DTBP), the Lewis base-borane is p-dimethylaminopyridine-borane (DMAP-BH3), the thiol is 2-methoxybenzenethiol, and the additive is sodium dihydrogen phosphate dihydrate.

[0011] The structure of the olefin is as follows:

[0012]

[0013] Further, the molar ratio of 5- (acetyloxymethyl) furan-2-carboxylic acid ethyl ester, initiator, Lewis base-borane, thiol, additive and olefin is 1.0 : 1.0 : 2.0 : 0.2 : 1.2 : 5.0.

[0014] In step 1, the solvent 1 is acetonitrile.

[0015] Further, the concentration of 5- (acetyloxymethyl) furan-2-carboxylic acid ethyl ester in the reaction system is controlled at 0.067-0.1 mol / L.

[0016] In step 1, the heating reaction temperature is 120°C.

[0017] Step 2: The ethyl 5-(arylpropyl)furoate compound obtained in Step 1 and a base are added to solvent 2, the reaction is heated with stirring, and the reaction endpoint is determined by thin layer chromatography (TLC) spotting. The organic phase impurities are removed by extraction with dichloromethane, and then the pH of the aqueous phase is adjusted to 1-2 by adding a 1.0 M hydrochloric acid solution. The reaction solution is extracted again with dichloromethane, and the collected organic phase is concentrated. The product is concentrated without purification and is directly subjected to deprotection with a deprotection reagent to obtain the target product.

[0018] In Step 2, the base is potassium hydroxide; and the molar ratio of the ethyl 5-(arylpropyl)furoate compound to the base is 1.0:2.0-4.0.

[0019] In Step 2, solvent 2 is composed of methanol and water, and the volume ratio of the two is 4:1.

[0020] Further, the concentration of the ethyl 5-(arylpropyl)furoate compound in the reaction system is controlled to be 0.10-0.20 mol / L.

[0021] In Step 2, the heating reaction temperature is 60°C.

[0022] In Step 2, the deprotection process is divided into two routes according to the different R groups:

[0023] Route one: when the R group is methoxy (R = OMe), the 5-(arylpropyl)furoic acid intermediate is added to solvent 3, and 5 equivalents of boron tribromide are added at reaction temperature 3. The reaction endpoint is determined by thin layer chromatography (TLC) spotting. After the reaction is completed, water is added to quench the reaction, dichloromethane is used for extraction, and the collected organic phase is concentrated by rotary evaporation to obtain 5-(3-(4-hydroxyphenyl)propyl)furan-2-carboxylic acid.

[0024] Route two: when the R group is tert-butoxycarbonylamino (R = NHBoc), the 5-(arylpropyl)furoic acid intermediate is added to solvent 4, and 20 equivalents of trifluoroacetic acid are added at reaction temperature 4. The reaction endpoint is determined by thin layer chromatography (TLC) spotting, and then the solvent is removed by rotary evaporation to obtain 5-(3-(4-aminophenyl)propyl)furan-2-carboxylic acid.

[0025] In Route one, the solvent 3 is dichloromethane, and the reaction temperature 3 is -78°C to room temperature.

[0026] In Route two, the solvent 4 is dichloromethane, and the reaction temperature 4 is room temperature.

[0027] The synthesis route is as follows:

[0028]

[0029] The above process can be represented by the reaction formula as follows:

[0030] Synthesis of 5-(3-(4-hydroxyphenyl)propyl)furan-2-carboxylic acid:

[0031]

[0032] Synthesis of 5-(3-(4-hydroxyphenyl)propyl)furan-2-carboxylic acid:

[0033]

[0034] The high-efficiency dehydroxyalkylation of ethyl 5-(acetyloxymethyl)furan-2-carboxylate is developed for the first time by using the method of the present application, not only the development of bio-based polymer monomer is completed, but also the conversion of cheap and easy-to-obtain furan bio-based molecules to high-value-added products is realized. DETAILED DESCRIPTION

[0035] The technical solutions in the embodiments of the present application will be clearly and completely described below in combination with the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application. Example 1

[0036] The synthesis steps of ethyl 5-(3-(4-methoxyphenyl)propyl)furan-2-carboxylate in this embodiment are as follows:

[0037]

[0038] Under a nitrogen atmosphere, 5-(acetyloxymethyl)furan-2-carboxylic acid ethyl ester (0.2 mmol), dimethylaminopyridine-borane (2 equivalents), sodium dihydrogen phosphate dihydrate (1.2 equivalents), acetonitrile (3 mL), p-methoxystyrene (5 equivalents), di-tert-butyl peroxide (1 equivalent), 2-methoxybenzenethiol (0.2 equivalent) were added into a 10 mL Schlenk reaction tube, and then the reaction vessel was kept in a nitrogen environment by replacing the gas, and the reaction bottle was placed in an oil bath at 120℃ for 12 h. The reaction end point was determined by thin layer chromatography (TLC) point plate, and then petroleum ether / ethyl acetate (50:1 by volume) was used as the eluent, and the product was separated by silica gel column to obtain ethyl 5-(3-(4-methoxyphenyl)propyl)furan-2-carboxylate.

[0039] The product yield is 51%, white liquid; 1 H NMR (400 MHz, CDCl3) δ 1.36 (3H, t, J= 7.2Hz), 1.94-2.01 (2H, m), 2.61 (2H, t, J = 8.0 Hz), 2.70 (2H, t, J = 8.0 Hz), 3.79(3H, s), 4.34 (2H, q, J = 7.2 Hz), 6.11-6.13 (1H, m), 6.81-6.85 (2H, m), 7.08-7.11 (3H, m); 13 C NMR (100 MHz, CDCl3) δ 14.4, 27.6, 29.5, 34.2, 55.2, 60.7,107.6, 113.7, 119.0, 129.3, 133.5, 143.2, 157.8, 158.9, 161.0.

[0040] The synthesis of (3-(4-hydroxyphenyl)propyl)furan-2-carboxylic acid in this example is as follows:

[0041]

[0042] Under a nitrogen atmosphere, 5-(3-(4-methoxyphenyl)propyl)furan-2- carboxylic acid ethyl ester (1.0 mmol), potassium hydroxide (4 equivalents), methanol (4 mL) and water (1 mL) were added to a reaction vessel, and the reaction mixture was stirred at 60°C for 18 h. After the reaction was completed, the reaction solution was extracted with dichloromethane three times, and the impurities in the organic phase were removed, then 1.0 M hydrochloric acid solution was added to the aqueous phase, and the solution pH was adjusted to 1-2, and then the ester hydrolysis product was extracted with dichloromethane again. Under a nitrogen atmosphere, the product was added to a reaction bottle, and the reaction mixture was stirred at -78°C for 30 min, then boron tribromide (5 equivalents) was added dropwise, and the reaction was continued at -78°C for 2 h, then the temperature was raised to room temperature and the reaction was continued. After 6 h, water was slowly added to quench, and the filtrate was extracted with dichloromethane three times, and the collected organic phase was concentrated by rotary evaporation to obtain (3-(4-hydroxyphenyl)propyl)furan-2-carboxylic acid.

[0043] The product yield was 83%, white solid; 1 H NMR(400 MHz, CDCl3)δ 1.95-2.02 (2H, m), 2.61(2H, t, J = 7.6 Hz), 2.72 (2H, t, J = 7.6 Hz), 6.18 (1H, d, J = 3.6 Hz), 6.76 (2H,d,J = 7.6 Hz), 7.05 (2H, d, J = 7.6 Hz), 7.23 (1H, d, J = 3.6 Hz); 13 C NMR (100 MHz,(CD3)2SO) δ 27.0, 29.4, 33.6, 108.0, 115.1, 118.9, 129.2, 131.4, 143.3, 155.4,159.3, 160.3. Example 2:

[0044] The synthesis of 5-(3-(4-(tert-butoxycarbonyl)amino)phenyl)propyl)furan-2- carboxylic acid ethyl ester in this example is as follows:

[0045]

[0046] Into a 10 mL Schlenk tube, 5-(acetyloxymethyl)furan-2-carboxylic acid ethyl ester (0.2 mmol), dimethylaminopyridine-borane (2 eq), sodium dihydrogen phosphate dihydrate (1.2 eq), acetonitrile (3 mL) were added, then tert-butyl (4-vinylphenyl)carbamate (5 eq), di-tert-butyl peroxide (1 eq), 2-methoxybenzenethiol (0.2 eq) were added, and the reaction vessel was kept under nitrogen atmosphere by replacing the air. The reaction bottle was placed in an oil bath at 120 °C for 12 h. The reaction end point was determined by thin layer chromatography (TLC) spot plate, then petroleum ether / ethyl acetate (50:1 by volume) was used as eluent, and the product was separated by silica gel column to obtain 5-(3-(4-(tert-butoxycarbonyl)amino)phenyl)propyl)furan-2-carboxylic acid ethyl ester.

[0047] The product yield was 39%, white liquid; 1 H NMR(400 MHz, CDCl3) 1.36 (3H, t, J = 7.2 Hz),1.50 (9H, s), 1.92-2.00 (2H, m), 2.60 (2H, t, J = 7.6 Hz), 2.68 (2H, t, J = 7.6Hz), 4.34 (2H, q, J = 7.2 Hz), 6.11 (1H, d, J = 3.2 Hz), 6.53 (1H, s), 7.07-7.09(3H, m), 7.28 (2H, d, J= 8.0 Hz); 13 C NMR (100 MHz, CDCl3) δ 14.3, 27.6, 28.3,29.3, 34.4, 60.7, 80.3, 107.7, 118.7, 119.0, 128.9, 136.1, 136.3, 143.2,152.8, 158.9, 160.8.

[0048] The synthesis of 5-(3-(4-aminophenyl)propyl)furan-2-carboxylic acid in this example is as follows:

[0049]

[0050] To the reaction vessel was added 5-(3-(4-(tert-butoxycarbonyl)amino)phenyl)propyl)furan-2-carboxylic acid ethyl ester (1.0 mmol), potassium hydroxide (4 equivalents), methanol (4 mL) and water (1 mL) under a nitrogen atmosphere, and the reaction mixture was stirred at 60 °C for 18 h. After the reaction was completed, the reaction solution was extracted with dichloromethane, and the impurities in the organic phase were removed, then 1.0 M hydrochloric acid solution was added to the aqueous phase, and the solution pH was adjusted to 1-2, and then extracted with dichloromethane to obtain the ester hydrolysis product. Then the product was dissolved in a dichloromethane solution and stirred, and trifluoroacetic acid (20 equivalents) was added, and stirring was continued for two hours. After the reaction was completed, it was concentrated by rotary evaporation to obtain 5-(3-(4-aminophenyl)propyl)furan-2-carboxylic acid.

[0051] The product yield was 91%, a yellow solid; 1 H NMR(500 MHz, CD3OD)δ 1.85-1.91 (2H, m),2.57-2.60 (4H, m), 6.13 (1H, d, J = 2.5 Hz), 7.04 (1H, d, J = 2.5 Hz), 7.22-7.24(2H, m), 7.26-7.30 (2H, m); 13 C NMR (125 MHz, CD3OD) δ 28.4, 30.5, 35.5, 109.1,120.4, 123.6, 130.8, 131.3, 143.8, 144.8, 162.0, 162.1.

[0052] Currently, there are also many reports on furan-based polyesters and furan-based polyamides. As a class of bio-based polymers, they can be widely used in packaging materials, organic semiconductors, self-healing repair materials and other fields, and have become a research hotspot in today's polymer materials. For example, 2,5-furandicarboxylic acid, as a typical representative of biomass furan monomers, can be used to synthesize polyesters with different types of alcohol compounds such as ethylene glycol, neopentyl glycol, 1,4-cyclohexane diol, etc. The obtained polymers have good ductility, barrier properties and tensile strength. Bio-based furan polyamides have better solubility than petroleum-based polyamides and have been widely studied. The introduction of furan carboxylic acid into amide polymers usually forms amorphous or low-crystallinity materials. Intramolecular hydrogen bonds are formed between oxygen atoms in furan rings and hydrogen atoms in amide bonds, which usually reduce the thermal and mechanical properties of furan polyamides (Fang Y G, Yang C L, Lin J Y, et al. Research progress in synthesis and application of bio-based polyfuran polymers [J]. Polymer Bulletin, 2022, (05): 38-54.). The Robert group in Germany synthesized long-chain furan-based polyamides using long-chain 1,10-decanediol, which successfully inhibited the formation of intramolecular hydrogen bonds, thereby improving the crystallinity (Robert T. ACS Sustain Chem Eng, 2020, 8 ,10812-10821). The monomers reported in this invention have some similarities with the above-mentioned literature, also containing methylene long chains and carboxyl and hydroxyl functional groups, so they can be used to prepare long-chain furan-based polyesters and polyamides with similar properties.

[0053] Under the same conditions, any one of the above-mentioned olefins can be used to obtain the corresponding novel furan-based bio-based polymerization monomers, and the yield varies due to the use of different olefins. It should be pointed out that for ordinary skilled persons in the art, without departing from the concept of the present invention, some modifications and improvements can still be made, which are within the scope of protection of the present invention.

Claims

1. A method for synthesizing 5-(arylpropyl)furoic acid compounds, characterized by Comprising the following steps: Step 1: under nitrogen atmosphere, 5- (acetyloxymethyl) furan-2-carboxylic acid ethyl ester, initiator, Lewis base-borane, thiol, additive and olefin are added into solvent 1, the reaction is heated under stirring, the reaction endpoint is determined by thin layer chromatography, and the 5- (arylpropyl) furfuryl acid ethyl ester compound is obtained by silica gel column separation; Step 2: the 5- (arylpropyl) furfuryl acid ethyl ester compound obtained in step 1 and base are added into solvent 2, the reaction is heated under stirring, the reaction endpoint is determined by thin layer chromatography, the organic phase impurities are removed by dichloromethane extraction first, then the pH of the aqueous solution is adjusted to 1-2, dichloromethane extraction is performed again, and the collected organic phase is concentrated; a deprotection reagent is added to the concentrated product for deprotection to obtain the target product; In step 1, the initiator is di-t-butyl peroxide, the Lewis base-borane is p-dimethylaminopyridine-borane, the thiol is 2-methoxybenzenethiol, and the additive is sodium dihydrogen phosphate dihydrate; The structure of the olefin is as follows: ； The structure of the 5- (arylpropyl) furfuryl acid ethyl ester compound is as follows: ； In step 1, the molar ratio of 5- (acetyloxymethyl) furan-2-carboxylic acid ethyl ester, initiator, Lewis base-borane, thiol, additive and olefin is 1.0:1.0:2.0:0.2:1.2:5.0; In step 2, the base is potassium hydroxide; the molar ratio of 5- (arylpropyl) furfuryl acid ethyl ester compound and base is 1.0:2.0-4.0; The structure of the target product is as follows: 。 2. The synthesis method according to claim 1, characterized in that: The solvent 1 is acetonitrile.

3. The synthesis method according to claim 1, characterized in that: In step 1, the heating reaction temperature is 120℃.

4. The synthesis method according to claim 1, characterized in that: In step 2, the solvent 2 is composed of methanol and water in a volume ratio of 4:

1.

5. The synthesis method according to claim 1, characterized in that: In step 2, the heating reaction temperature is 60℃.

6. The synthesis method according to claim 1, characterized in that: In step 2, the deprotection process is divided into two routes according to the difference of R group: Route one: when R = OMe, the 5- (arylpropyl) furfuryl acid intermediate is added to solvent 3, and 5 equivalents of boron tribromide are added at reaction temperature 3, the reaction endpoint is determined by thin layer chromatography, water is added to quench the reaction after the reaction is completed, dichloromethane is used for extraction, and the collected organic phase is concentrated by rotary evaporation to obtain 5- (3- (4-hydroxyphenyl) propyl) furan-2-carboxylic acid; Route two: when R = NHBoc, the 5- (arylpropyl) furfuryl acid intermediate is added to solvent 4, 20 equivalents of trifluoroacetic acid are added at reaction temperature 4, the reaction endpoint is determined by thin layer chromatography, and then the solvent is removed by rotary evaporation to obtain 5- (3- (4-aminophenyl) propyl) furan-2-carboxylic acid; The synthesis route is as follows: 。 7. The synthesis method according to claim 6, characterized in that: In Route 1, the solvent 3 is dichloromethane, and the reaction temperature 3 is from -78 °C to room temperature. In Route 2, the solvent 4 is dichloromethane, and the reaction temperature 4 is room temperature.

Images