CN110526886B - Method for synthesizing 1-oxo-1, 3-dihydro-3-hydroxybenzofuran-5-formic acid - Google Patents
Method for synthesizing 1-oxo-1, 3-dihydro-3-hydroxybenzofuran-5-formic acid Download PDFInfo
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Abstract
The invention discloses a method for synthesizing 1-oxo-1, 3-dihydro-3-hydroxybenzofuran-5-formic acid, which comprises the following steps: mixing 2, 5-dihalotoluene, glacial acetic acid, acetic anhydride and concentrated sulfuric acid, adding chromium trioxide for oxidation reaction to prepare 2, 5-dihalo-diacetoxy methylbenzene, catalyzing the 2, 5-dihalo-diacetoxy methylbenzene by using a palladium catalyst to prepare 4-halogen-3-formylbenzoic acid, and catalyzing the 4-halogen-3-formylbenzoic acid by using the palladium catalyst to prepare 1-oxo-1, 3-dihydro-3-hydroxybenzofuran-5-formic acid. The preparation method has the advantages of simple requirements on instruments and equipment, easily obtained raw materials, convenience for large-scale preparation, good economic benefit, higher product yield and simple post-reaction treatment.
Description
Technical Field
The invention relates to a method for synthesizing 1-oxo-1, 3-dihydro-3-hydroxybenzofuran-5-formic acid, belonging to the field of organic synthesis.
Background
The terephthalic acid compound is an important dye, drug and chemical intermediate. Has potential application value in the field of synthesis of multifunctional Metal-Organic frameworks (MOFs). The pre-modification of organic reactive functional groups at the side of terephthalic acid is a common research strategy, and the introduction of new functional groups, especially chemically active groups, brings new properties to the new materials.
BaogangWang et al reported in 2014 the synthesis of 1-oxo-1, 3-dihydrobenzofuran-5-carboxylic acid with a different substituent at position 3, wherein the yield of 1-oxo-1, 3-dihydro-3-hydroxybenzofuran-5-carboxylic acid is 20%, and the synthetic route is as follows:
in 2016, Stephen J.D., work, 2, 5-dibromobenzaldehyde is used as a raw material, and isomers of 2-formyl terephthalic acid are synthesized under the conditions of palladium acetate, 4, 5-bis (diphenylphosphino) -9, 9-dimethylxanthene, carbon monoxide and the like, wherein the route is as follows:
at present, no mature method and related patents exist in China for the synthesis report of 1-oxo-1, 3-dihydro-3-hydroxybenzofuran-5-formic acid.
Disclosure of Invention
In view of the above, the present invention provides a method for synthesizing 1-oxo-1, 3-dihydro-3-hydroxybenzofuran-5-formic acid, which uses cheap 2, 5-dihalotoluene as a raw material, skillfully combines multiple reactions, and develops a new synthetic route of 1-oxo-1, 3-dihydro-3-hydroxybenzofuran-5-formic acid through elaborate tests.
Specifically, the invention adopts the following technical scheme:
a preparation method of 1-oxo-1, 3-dihydro-3-hydroxybenzofuran-5-formic acid comprises the following steps:
(1) adding 2, 5-dihalotoluene into a mixed solution of glacial acetic acid, acetic anhydride and concentrated sulfuric acid, adding chromium trioxide at 0-5 ℃, carrying out oxidation reaction for 2-24h at 23-25 ℃ (preferably 25 ℃) to obtain a reaction solution, and mixing the reaction solution with the following components: adding ice water with the volume ratio of 1:5-10 into the ice water, stirring until light green precipitates appear, ultrasonically oscillating, performing suction filtration, washing with deionized water to obtain dried light green solids, washing with an organic solvent I, and performing suction filtration after ultrasonic oscillation to obtain 2, 5-dihalo-diacetoxy methylbenzene;
(2) mixing 2, 5-dihalogen-diacetoxymethylbenzene with a palladium catalyst, a phosphine ligand, a second organic solvent, water and alkali under the protection of protective gas, pumping out, filling carbon monoxide gas for 5min to obtain a carbon monoxide environment, reacting at 65-110 ℃ for 1.5-4h under the carbon monoxide environment, filling carbon monoxide gas for 5min every 30min in the reaction process, removing the second organic solvent after the reaction is finished, adjusting the pH value to 1-4 with 10% hydrochloric acid, pumping filtering, washing with deionized water, and drying at 60 ℃ for 8-12h to obtain 4-halo-3-formylbenzoic acid;
(3) mixing 4-bromo-3-formylbenzoic acid with a palladium catalyst, a phosphine ligand, an organic solvent II, water and alkali under the protection of protective gas, pumping out, filling carbon monoxide gas for 5min to obtain a carbon monoxide environment, reacting at 65-110 ℃ for 6-12h under the carbon monoxide environment, filling carbon monoxide gas for 5min every 30min in the reaction process, removing the organic solvent II after the reaction is finished, adjusting the pH value to 1-4 by using 10% hydrochloric acid, pumping and filtering, washing by using deionized water, and extracting by using ethyl acetate or dichloromethane to obtain the 1-oxo-1, 3-dihydro-3-hydroxybenzofuran-5-formic acid.
Taking 2, 5-dibromotoluene as an example, the route of the invention is as follows:
the invention has the beneficial effects that:
(1) the reaction can obtain the 1-oxo-1, 3-dihydro-3-hydroxybenzofuran-5-formic acid with higher yield, the treatment after the reaction is simple, and the pure target product can be obtained only by washing, extracting and filtering;
(2) the method has simple synthesis, easily obtained raw materials and convenient large-scale preparation;
(3) the selection method has simple requirements on instruments and equipment, has great advantages in reaction cost and good economic benefits.
Further, in the step (1), the 2, 5-dihalotoluene is 2, 5-dichlorotoluene or 2, 5-dibromotoluene;
the organic solvent I is any one of petroleum ether, n-hexane or cyclohexane;
in the step (2) and/or the step (3), the protective gas is any one of nitrogen, argon or neon;
the palladium catalyst is any one of palladium chloride, palladium acetate, tetratriphenylphosphine palladium, [2,2 '-bis (diphenylphosphino) -1,1' -binaphthyl ] palladium dichloride, chlorine (1, 5-cyclooctadiene) methyl palladium (II), bis (dicyclohexylamine) palladium acetate (II), tris (dibenzylidene-base acetone) dipalladium and bis (2-methallyl) palladium dichloride;
the phosphine ligand is one of 4, 5-bis (diphenylphosphino) -9, 9-dimethylxanthene, p-xylylene bis (triphenylphosphonium bromide), p-xylylene bis (triphenylphosphonium chloride), bis (1-naphthyl) phosphine chloride, tris (4-methylphenyl) phosphine oxide or tetratriphenylphosphine;
the organic solvent II is a mixed solvent formed by mixing any one of tetrahydrofuran or dimethyl sulfoxide and water in a volume ratio of 10: 1;
the alkali is any one of trimethylamine, triethylamine or sodium carbonate.
The method has the further beneficial effects of easily obtained raw materials, short reaction time, simple post-treatment and no need of special purification means.
Further, in the step (1), the molar ratio of glacial acetic acid, acetic anhydride, concentrated sulfuric acid to 2, 5-dihalotoluene is 21-25:13-15:5-8: 1;
the molar ratio of the chromium trioxide to the 2, 5-dihalotoluene is 3-5: 1;
in the step (2) and/or the step (3), the molar ratio of the 2, 5-dihalo-diacetoxymethylbenzene, the palladium catalyst and the phosphine ligand is 1:0.05-0.2: 0.1;
the addition amount of the organic solvent II is that 20mL of the organic solvent II is added into every 1g of 2, 5-dihalo-diacetoxy methylbenzene;
when the alkali is trimethylamine or triethylamine, the volume ratio of the alkali to water is 1:1, and when the alkali is sodium carbonate, the mass ratio of the alkali to water is 2: 1.
The method has the further advantages of reducing the generation of byproducts, short reaction time, simple post-treatment and no need of special purification means.
Further, the operation of removing the second organic solvent in the step (2) and/or the step (3) is as follows: when the organic solvent II is tetrahydrofuran, removing the organic solvent II by rotary evaporation, and adding water to dilute to 10 times of the original volume;
when the organic solvent II is dimethyl sulfoxide, adding water for dilution, adjusting the pH value to 10-12 by using a strong alkali dilute solution, and washing for three times by using the organic solvent IV, wherein the strong alkali dilute solution is a sodium hydroxide or potassium hydroxide solution with the concentration of 2 mol/L; the organic solvent IV is any one of ethyl acetate, diethyl ether, dichloromethane or trichloromethane.
Drawings
FIG. 1 is a nuclear magnetic resonance hydrogen spectrum of 2-formylterephthalic acid obtained in example 1 of the present invention;
FIG. 2 is a NMR spectrum of 1-oxo-1, 3-dihydro-3-hydroxybenzofuran-5-carboxylic acid obtained in example 1 of the present invention.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
In the following examples, 4, 5-bis (diphenylphosphino) -9, 9-dimethylxanthene, p-xylylene bis (triphenylphosphonium bromide), p-xylylene bis (triphenylphosphonium chloride), bis (1-naphthyl) phosphine chloride, tris (4-methylphenyl) phosphine oxide or tetratriphenylphosphine (97%, Shaoshima chemical science and technology, Inc.); palladium chloride, palladium acetate, palladium tetrakistriphenylphosphine, 2 '-bis (diphenylphosphino) -1,1' -binaphthyl]Palladium dichloride, chloro (1, 5-cyclooctadiene) methyl palladium (II), bis (dicyclohexylamine) palladium (II) acetate, tris (dibenzylidene-base acetone) dipalladium, bis (2-methallyl) palladium dichloride (98%, Arkpharm); 2, 5-dibromotoluene (70%, EAP Chem Corp.); acetic anhydride, chromium trioxide (analytical grade, chemical reagent of national pharmaceutical group); concentrated sulfuric acid H2SO4(Yongda Chemicals Co., Tianjin); glacial acetic acid, anhydrous potassium carbonate (analytical grade, Tianjin, Dalochi chemical reagent works); tetrahydrofuran, petroleum ether, n-hexane, and ethylEthyl acetate, dichloromethane, anhydrous sodium sulfate (analytical purity, Tianjin Beichen Square reagent factory); n, N-dimethylformamide (99.5%, analytical purity, njn chemical reagents ltd, tianjin); hydrochloric acid HCl (98%, gagao gao qiao chemical limited); anhydrous methanol, triethylamine, sodium hydroxide, sodium chloride, dimethyl sulfoxide (analytically pure, shentai chemical reagents science and technology limited, Tianjin).
DHG-9070A electric heating constant temperature air-blast drying oven (Steud City Instrument, Inc.); DF-101S heat collection type magnetic heating stirrer (produced by Baita Xinbao instruments in gold Tan); a rotary evaporator RE-52AA (Shanghai Yangrong Biochemical apparatus); SH2-D (III) circulating water type vacuum pump (Oncorhyne instruments, Inc.; Hill.); model 85-1 magnetic stirrers (Shanghai cereal vapor instruments, Inc.); KQ-400KDE type high power digital control ultrasonic cleaner (Kunshan ultrasonic instruments Co., Ltd.); ZF-7A portable ultraviolet monitoring lamp (Shanghai Baoshan Gucun electro-optical instrument factory); CP214 electronic balance (aohaus instruments ltd).
Example 1
The preparation method of 1-oxo-1, 3-dihydro-3-hydroxybenzofuran-5-formic acid comprises the following steps:
(1) 2, 5-dibromotoluene (14.5g,0.058mol), glacial acetic acid (87.07g,1.45mol), acetic anhydride (77.8g,0.76mol) and concentrated sulfuric acid (30.8g,0.31mol) were sequentially added to a 250mL single-neck flask, and the reaction system was cooled to 0-5 ℃ in an ice-water bath. Slowly adding chromium trioxide (17.5g,0.175mol) in batches under vigorous stirring, wherein the adding process lasts for 30min, and the reaction temperature is controlled at 0-5 ℃ in an ice-water bath; the final reaction was stirred at this temperature for 2h and then at room temperature for 2 h. Slowly pouring the reaction solution into ice water (850mL), quickly stirring to obtain a large amount of light green solid, placing the light green solid into ultrasonic waves to vibrate for 20min, performing suction filtration to obtain the light green solid, washing the light green solid in batches by using 200mL of deionized water, and fully drying the obtained solid. And uniformly dispersing the obtained solid by using normal hexane, oscillating the mixed solution in an ultrasonic instrument for 1h, and performing suction filtration to obtain 19.1g of white solid 2, 5-dibromo-diacetoxymethylbenzene with the yield of 90%.
(2) 2, 5-dibromo-diacetoxymethylbenzene (3g,8mmol), palladium acetate (89.8mg,0.4mmol) and 4, 5-bis (diphenylphosphino) -9, 9-dimethylxanthene (463mg,0.8mmol) were placed in a two-necked flask, and gas was purged 3 times under nitrogen protection, followed by addition of tetrahydrofuran (50mL) and deionized water (10mL) which had been previously degassed, and gas was again purged 3 times. The reactor was then evacuated of nitrogen at room temperature until the reaction solution bubbled a lot of gas, then one atmosphere of carbon monoxide gas was charged, triethylamine (6mL) was added, the system was purged 3 more times, and the final reaction solution was reacted at 65 ℃ for 20h in one atmosphere of carbon monoxide in an oil bath. After the reaction is finished, tetrahydrofuran is removed through reduced pressure distillation, the residual liquid is filtered, water is added for dilution, the pH value is adjusted to 11, ethyl acetate is used for washing a water phase for 3 times, the water phase is repeatedly filtered to be a clear solution, the pH value of the water phase is adjusted to 3, a large amount of white solids are separated out, the filtration is quickly carried out, a filter cake is washed by a large amount of deionized water, and the filter cake is dried for 10 hours in a vacuum drying oven at 60 ℃, so that 1.48g of 4-bromo-3-formylbenzoic acid is obtained, and.
The result of the nuclear magnetic resonance hydrogen spectrum of the product is as follows:1HNMR(400MHz,DMSO-d6) δ 13.54(br,1H),10.24(s,1H),8.31(s,1H),8.07(d, J ═ 8.0Hz,1H),7.93(d, J ═ 8.0Hz,1H), the spectrum is as in fig. 1.
(3) 4-bromo-3-formylbenzoic acid (1.8g,8mmol), palladium acetate (89.8mg,0.4mmol) and 4, 5-bis (diphenylphosphino) -9, 9-dimethylxanthene (463mg,0.8mmol) were placed in a two-necked flask and purged 3 times under nitrogen, followed by addition of tetrahydrofuran (50mL) and deionized water (10mL) which had been previously degassed and then purged 3 times again. The reactor was then evacuated of nitrogen at room temperature until the reaction solution bubbled a lot of gas, then one atmosphere of carbon monoxide gas was charged, triethylamine (6mL) was added, the system was purged 3 more times, and the final reaction solution was reacted at 65 ℃ in an oil bath under one atmosphere of carbon monoxide for 6 h. After the reaction is finished, tetrahydrofuran is removed through reduced pressure distillation, the residual liquid is filtered, water is added for dilution, the pH value is adjusted to 11, ethyl acetate is used for washing the water phase for 3 times, the water phase is repeatedly filtered to be a clear solution, the pH value of the water phase is adjusted to 3, ethyl acetate is used for extraction for three times, the organic phase is dried by anhydrous sodium sulfate, filtration and rotary evaporation are carried out, and 1.4g of the target compound is obtained, wherein the yield is 90%.
Product nuclear magnetic resonance hydrogen spectrum knotThe fruit is as follows:1H NMR(400MHz,DMSO-d6) δ 13.61(s,1H),8.47-8.22(m,1H),8.20(d, J ═ 8.0Hz,1H),8.17(s,1H),7.95(d, J ═ 8.0Hz,1H),6.77(s,1H), the spectrum is as in fig. 2.
Example 2
The preparation method of 1-oxo-1, 3-dihydro-3-hydroxybenzofuran-5-formic acid comprises the following steps:
(1) 2, 5-dichlorotoluene (9.34g,0.058mol), glacial acetic acid (87.08g,1.45mol), acetic anhydride (88.82g,0.87mol) and concentrated sulfuric acid (46.1g,0.46mol) were sequentially added to a 250mL single-neck flask, and the reaction system was cooled to 0-5 ℃ by an ice-water bath. Slowly adding chromium trioxide (29g,0.29mol) in batches under vigorous stirring, wherein the adding process lasts for 30min, and the reaction temperature is controlled at 0-5 ℃ in an ice-water bath; the final reaction was stirred at this temperature for a further 2h, then at room temperature for 24 h. Slowly pouring the reaction solution into ice water (1700mL), quickly stirring to obtain a large amount of light green solid, placing the light green solid into ultrasonic waves to vibrate for 20min, performing suction filtration to obtain the light green solid, washing the light green solid in batches by using 200mL of deionized water, and fully drying the obtained solid. The obtained solid is uniformly dispersed by petroleum ether, the mixed solution is vibrated for 1 hour in an ultrasonic instrument and is filtered, 13.7g of white solid 2, 5-dichlorodiacetoxymethylbenzene is obtained, and the yield is 85 percent.
(2) 2, 5-dichloro-diacetoxymethylbenzene (3g,8mmol), palladium tetratriphenylphosphine (462mg,0.4mmol), p-xylylenebis (triphenylphosphine chloride) (560mg,0.8mmol) and sodium carbonate (5g) were placed in a two-necked flask and purged 3 times under nitrogen protection, and then dimethyl sulfoxide (50mL) and deionized water (10mL) which had been previously degassed were added and purged 3 times again. Then the nitrogen in the reactor is evacuated at room temperature, the carbon monoxide gas at one atmosphere is charged, the system is pumped and exchanged for 3 times, and the final reaction liquid is reacted for 4 hours at 110 ℃ in the carbon monoxide gas at one atmosphere by oil bath control. After the reaction is finished, 500mL of water is added into the reaction solution, insoluble substances are removed by filtration, the pH value is adjusted to 11, the methylene dichloride is used for washing the water phase for 3 times, the pH value of the water phase is adjusted to 3, a large amount of white solid is separated out, the filtration is rapidly carried out, a large amount of deionized water is used for washing a filter cake, and the filter cake is dried in a vacuum drying oven at 60 ℃ for 10 hours to obtain 1.48g of 4-chloro-3-formylbenzoic acid with the yield.
(3) 4-chloro-3-formylbenzoic acid (1.84g,10mmol), tetratriphenylphosphine palladium (578mg,0.5mmol), p-xylylenebis (triphenylphosphine chloride) (700mg,1.0mmol) and sodium carbonate (5g) were placed in a two-necked flask and purged 3 times under nitrogen protection, then dimethyl sulfoxide (50mL) previously degassed and deionized water (10mL) were added and purged 3 times again. Then the nitrogen in the reactor is evacuated at room temperature, the carbon monoxide gas at one atmosphere is charged, the system is pumped and exchanged for 3 times, and the final reaction solution is reacted for 12 hours in the carbon monoxide gas at one atmosphere in an oil bath controlled at 110 ℃. After the reaction, the reaction solution was poured into 500mL of water, repeated filtration was performed to remove insoluble materials, the pH of the filtrate was adjusted to 11, the aqueous phase was washed with dichloromethane 3 times, the aqueous phase was repeatedly filtered to obtain a clear solution, the pH of the aqueous phase was adjusted to 3, dichloromethane was extracted three times, the organic phase was dried over anhydrous sodium sulfate, filtered, and rotary-evaporated to obtain 1.6g of the target compound with a yield of 82%.
The result of the nuclear magnetic resonance hydrogen spectrum of the product is as follows:1H NMR(400MHz,DMSO-d6)δ13.61(s,1H),8.47-8.22(m,1H),8.20(d,J＝8.0Hz,1H),8.17(s,1H),7.95(d,J＝8.0Hz,1H),6.77(s,1H)。
example 3
The preparation method of 1-oxo-1, 3-dihydro-3-hydroxybenzofuran-5-formic acid comprises the following steps:
(1) the difference from the step (1) in example 1 is that the amount of chromium trioxide is 23.2g and 0.232mol, the obtained solid is uniformly dispersed with petroleum ether, the mixed solution is shaken for 1h in an ultrasonic instrument and filtered by suction, and 19.3g of white solid 2, 5-dibromo-diacetoxymethylbenzene is obtained with a yield of 91%.
(2) The difference from step (2) in example 1 was that the palladium reagent was palladium chloride (71mg,0.4mmol), the phosphine ligand was tetratriphenylphosphine (463mg,0.8mmol), the base was trimethylamine (6mL), and the reaction time was 4h, whereby 1.28g of 2-formylterephthalic acid was obtained in a yield of 82%.
(3) The difference from step (3) of example 1 is that the palladium reagent was [2,2 '-bis (diphenylphosphino) -1,1' -binaphthyl ] palladium dichloride (320mg,0.4mmol) and the phosphine ligand was bis (1-naphthyl) phosphine chloride (257mg,0.8mmol), and reacted at 65 ℃ for 16 h. 1.1g of the objective compound was obtained in a yield of 71%.
The result of the nuclear magnetic resonance hydrogen spectrum of the product is as follows:1H NMR(400MHz,DMSO-d6)δ13.61(s,1H),8.47-8.22(m,1H),8.20(d,J＝8.0Hz,1H),8.17(s,1H),7.95(d,J＝8.0Hz,1H),6.77(s,1H)。
example 4
The preparation method of 1-oxo-1, 3-dihydro-3-hydroxybenzofuran-5-formic acid comprises the following steps:
(1) same as in step (1) of example 1.
(2) The difference from step (2) in example 1 was that the palladium reagent tetrakistriphenylphosphine palladium (462mg,0.4mmol), the phosphine ligand tetrakistriphenylphosphine (463mg,0.8mmol) and the reaction time 1.5h gave 1.3g of 2-formylterephthalic acid in 83% yield.
(3) The difference from step (3) of example 1 is that the palladium reagent is tris (dibenzylidene-base acetone) dipalladium (286mg,0.4mmol) and the phosphine ligand is tris (4-methylphenyl) phosphine oxide (257mg,0.8mmol) and reacted at 65 ℃ for 16 h. The desired compound (1.33 g) was obtained in 86% yield.
The result of the nuclear magnetic resonance hydrogen spectrum of the product is as follows:1H NMR(400MHz,DMSO-d6)δ13.61(s,1H),8.47-8.22(m,1H),8.20(d,J＝8.0Hz,1H),8.17(s,1H),7.95(d,J＝8.0Hz,1H),6.77(s,1H)。
example 5
The preparation method of 1-oxo-1, 3-dihydro-3-hydroxybenzofuran-5-formic acid comprises the following steps:
(1) same as in step (1) of example 1.
(2) The difference from step (2) in example 1 was that a palladium reagent, chloro (1, 5-cyclooctadiene) methyl palladium (106mg,0.4mmol), a phosphine ligand, p-xylylene bis (triphenylphosphonium bromide) (631mg,0.8mmol) and a reaction time of 3 hours, gave 1.26g of 2-formylterephthalic acid in a yield of 81%.
(3) The difference from step (3) of example 1 is that the palladium reagent is palladium bis (dicyclohexylamine) acetate (234mg,0.4mmol) and the phosphine ligand is bis (1-naphthyl) phosphine chloride (257mg,0.8mmol) and reacted at 65 ℃ for 16 h. 1.13g of the objective compound was obtained in a yield of 73%.
The result of the nuclear magnetic resonance hydrogen spectrum of the product is as follows:1H NMR(400MHz,DMSO-d6)δ13.61(s,1H),8.47-8.22(m,1H),8.20(d,J＝8.0Hz,1H),8.17(s,1H),7.95(d,J＝8.0Hz,1H),6.77(s,1H)。
Claims (9)
1. a method for synthesizing 1-oxo-1, 3-dihydro-3-hydroxybenzofuran-5-carboxylic acid, comprising the steps of:
(1) adding 2, 5-dihalogen toluene into a mixed solution of glacial acetic acid, acetic anhydride and concentrated sulfuric acid, adding chromium trioxide for oxidation reaction to obtain a reaction solution, adding the reaction solution into ice water, stirring until a light green precipitate appears, ultrasonically oscillating, filtering, washing with deionized water to obtain a dried light green solid, dissolving with an organic solvent I, and filtering after ultrasonically oscillating to obtain 2, 5-dihalogen-diacetoxy methylbenzene;
(2) mixing 2, 5-dihalogen-diacetoxymethylbenzene with a palladium catalyst, a phosphine ligand, a second organic solvent, water and alkali under the protection of protective gas, reacting under a carbon monoxide environment, removing the second organic solvent after the reaction is finished, adjusting the pH value to 1-4, performing suction filtration, washing with deionized water, and drying to obtain 4-halo-3-formylbenzoic acid;
(3) mixing 4-halogen-3-formylbenzoic acid with a palladium catalyst, a phosphine ligand, an organic solvent II, water and alkali under the protection of protective gas, reacting under the environment of carbon monoxide, removing the organic solvent II after the reaction is finished, adjusting the pH value to 1-4, performing suction filtration, washing with deionized water, and extracting with an organic solvent III to obtain 1-oxo-1, 3-dihydro-3-hydroxybenzofuran-5-formic acid;
in the step (1), the molar ratio of the glacial acetic acid, the acetic anhydride, the concentrated sulfuric acid and the 2, 5-dihalotoluene is 21-25:13-15:5-8: 1;
the molar ratio of the chromium trioxide to the 2, 5-dihalotoluene is 3-5: 1;
the mass ratio of the reaction liquid to the ice water is 1: 5.
2. The process for synthesizing 1-oxo-1, 3-dihydro-3-hydroxybenzofuran-5-carboxylic acid according to claim 1, wherein the 2, 5-dihalotoluene in the step (1) is 2, 5-dichlorotoluene or 2, 5-dibromotoluene;
the first organic solvent is any one of petroleum ether, n-hexane or cyclohexane.
3. The method for synthesizing 1-oxo-1, 3-dihydro-3-hydroxybenzofuran-5-carboxylic acid according to claim 1, wherein the temperature of the mixed solution is 0-5 ℃ when the chromium trioxide is added in the step (1);
the oxidation reaction temperature is 23-25 ℃, and the time is 2-24 h.
4. The method for synthesizing 1-oxo-1, 3-dihydro-3-hydroxybenzofuran-5-carboxylic acid according to claim 1, wherein the shielding gas in step (2) and/or step (3) is any one of nitrogen, argon or neon;
the palladium catalyst is any one of palladium chloride, palladium acetate, tetratriphenylphosphine palladium, 2 '-bis (diphenylphosphino) -1,1' -binaphthyl ] palladium dichloride, chlorine (1, 5-cyclooctadiene) methyl palladium (II), bis (dicyclohexylamine) palladium acetate (II), tris (dibenzylidene-base acetone) dipalladium and bis (2-methallyl) palladium dichloride;
the phosphine ligand is one of 4, 5-bis (diphenylphosphino) -9, 9-dimethylxanthene, p-xylylene bis (triphenylphosphonium bromide), p-xylylene bis (triphenylphosphonium chloride), bis (1-naphthyl) phosphine chloride, tris (4-methylphenyl) phosphine oxide or tetratriphenylphosphine;
the organic solvent II is a mixed solvent formed by mixing any one of tetrahydrofuran or dimethyl sulfoxide and water in a volume ratio of 10: 1;
the alkali is any one of trimethylamine, triethylamine or sodium carbonate.
5. The method for synthesizing 1-oxo-1, 3-dihydro-3-hydroxybenzofuran-5-carboxylic acid according to claim 4, wherein the molar ratio of the 2, 5-dihalo-diacetoxymethylbenzene, the palladium catalyst and the phosphine ligand in step (2) and/or step (3) is 1:0.05: 0.1;
the addition amount of the organic solvent II is that 20mL of the organic solvent II is added into every 1g of 2, 5-dihalo-diacetoxy methylbenzene;
the volume ratio of the alkali to water is 1:1 when the alkali is trimethylamine or triethylamine, and the mass ratio of the alkali to water is 1:2 when the alkali is sodium carbonate.
6. The method for synthesizing 1-oxo-1, 3-dihydro-3-hydroxybenzofuran-5-carboxylic acid as claimed in claim 5, wherein in the step (2) and/or the step (3), the carbon monoxide atmosphere is obtained by evacuating and charging carbon monoxide gas for 5 min;
the reaction temperature is 65-110 ℃, the reaction time is 1.5-4h, and carbon monoxide gas is charged for 5min every 30min in the reaction process;
the operation of adjusting the pH value to 1-4 is to adjust the pH value to 1-4 by 10% hydrochloric acid.
7. The method for synthesizing 1-oxo-1, 3-dihydro-3-hydroxybenzofuran-5-carboxylic acid according to claim 6, wherein the removing of the second organic solvent in step (2) and/or step (3) is: when the organic solvent II is tetrahydrofuran, removing the organic solvent II by rotary evaporation, and adding water to dilute to 10 times of the volume of the raw water;
when the organic solvent II is dimethyl sulfoxide, adding water for dilution, adjusting the pH value to 10-12 by using a strong alkali dilute solution, and washing three times by using the organic solvent IV.
8. The method for preparing 1-oxo-1, 3-dihydro-3-hydroxybenzofuran-5-carboxylic acid according to claim 7, wherein the diluted solution of strong base is a solution of sodium hydroxide or potassium hydroxide with a concentration of 2 mol/L;
the organic solvent IV is any one of ethyl acetate, diethyl ether, dichloromethane or trichloromethane.
9. The method for preparing 1-oxo-1, 3-dihydro-3-hydroxybenzofuran-5-carboxylic acid according to claim 1, wherein the drying in step (2) is performed at 60 ℃ for 8-12 h;
and (3) the organic solvent III is ethyl acetate or dichloromethane.
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