CN110526886A - A method of synthesis 1- oxo -1,3- dihydro-3-hydroxy benzofuran -5- formic acid - Google Patents
A method of synthesis 1- oxo -1,3- dihydro-3-hydroxy benzofuran -5- formic acid Download PDFInfo
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- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/87—Benzo [c] furans; Hydrogenated benzo [c] furans
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Abstract
The invention discloses a kind of synthesis 1- oxos -1; the method of 3- dihydro-3-hydroxy benzofuran -5- formic acid; the synthetic method includes: to take 2; 5- halogeno toluene, glacial acetic acid, acetic anhydride, concentrated sulfuric acid mixing; chromium trioxide oxidation reaction is added and is made 2; 5- dihalo--diacetoxyl methylbenzene; 2; 5- dihalo--via palladium-catalyzed dose of diacetoxyl methylbenzene, which is catalyzed, is made 4- halogen -3- formylbenzoate; 4- halogen -3- formylbenzoate is catalyzed obtained 1- oxo -1,3- dihydro-3-hydroxy benzofuran -5- formic acid for via palladium-catalyzed dose again.Preparation method of the invention requires simply instrument and equipment, and raw material is easy to get, and is convenient for large-scale preparation, and good in economic efficiency, products collection efficiency is higher, and post-reaction treatment is simple.
Description
Technical field
The present invention relates to a kind of methods of synthesis 1- oxo -1,3- dihydro-3-hydroxy benzofuran -5- formic acid, and belonging to has
Machine synthesizes field.
Background technique
Terephthaldehyde's acids compound is a kind of important dyestuff, drug and chemical intermediate.In multi-functional metal
The synthesis field of organic frame (Metal-Organic frameworks, MOFs) has potential application.To benzene two
The pre- modification that the side position of formic acid carries out organic active functional group is a kind of common research strategy, and new functional group is especially chemically
The introducing of the active group of matter is to this kind of new material bring new property.
BaogangWang et al. reported 3 1- oxo -1,3- dihydrobenzo furans containing different substituents in 2014
It mutters the synthesis of -5- formic acid formic acid, wherein the yield of 1- oxo -1,3- dihydro-3-hydroxy benzofuran -5- formic acid is 20%, is closed
It is as follows at route:
With 2,5- dibromo benzaldehyde for raw material in the work of Stephen J.D. in 2016, in palladium acetate, the bis- (hexichol of 4,5-
Base phosphine) it synthesizes under the conditions of -9,9- xanthphos and carbon monoxide etc., the isomers of 2- formoxyl terephthalic acid (TPA), road
Line is as follows:
The synthesis of 1- oxo -1,3- dihydro-3-hydroxy benzofuran -5- formic acid is reported at present, it is domestic not yet at
Ripe method and related patents.
Summary of the invention
In view of this, the present invention provides a kind of synthesis 1- oxo -1,3- dihydro-3-hydroxy benzofuran -5- formic acid
Method is that raw material dexterously together by multistep kind reaction bonded by testing meticulously, is opened with cheap 2,5- halogeno toluene
Issue a kind of synthetic route of new 1- oxo -1,3- dihydro-3-hydroxy benzofuran -5- formic acid.
Specifically, the present invention adopts the following technical scheme:
A kind of preparation method of 1- oxo -1,3- dihydro-3-hydroxy benzofuran -5- formic acid, includes the following steps:
(1) it takes 2,5- halogeno toluene to be added into the mixed liquor of glacial acetic acid, acetic anhydride and the concentrated sulfuric acid, is added three at 0-5 DEG C
Chromium oxide, 23-25 DEG C of (preferably 25 DEG C) oxidation reaction 2-24h, obtains reaction solution, by reaction solution with reaction solution: ice water 1:5-10
Volume ratio be added and stirred into ice water to there is light green precipitating, ultrasonic vibration is filtered and is washed with deionized, done
Light green solid after dry is washed with organic solvent one, is filtered after ultrasonic vibration, is obtained 2,5- dihalo--diacetoxyl methylbenzene；
(2) by 2,5- dihalo--diacetoxyl methylbenzene protection gas protection under with palladium catalyst, Phosphine ligands, You Jirong
Agent two, water and alkali mixing, are filled with CO gas 5min and obtain carbon monoxide environment, under carbon monoxide environment after evacuation
65-110 DEG C of reaction 1.5-4h, in reaction process, every 30min is filled with a CO gas 5min, removes after reaction
Organic solvent two is filtered, is washed with deionized water, 60 DEG C of dry 8-12h obtain 4- with 10% salt acid for adjusting pH value to 1-4
Halogen -3- formylbenzoate；
(3) by the bromo- 3- formylbenzoate of 4- protection gas protection under with palladium catalyst, Phosphine ligands, organic solvent two,
Water and alkali mixing, are filled with CO gas 5min and obtain carbon monoxide environment after evacuation, the 65-110 under carbon monoxide environment
DEG C reaction 6-12h, in reaction process, every 30min is filled with a CO gas 5min, removes organic solvent after reaction
Two, with 10% salt acid for adjusting pH value to 1-4, filters, extracted after being washed with deionized water by ethyl acetate or methylene chloride
To 1- oxo -1,3- dihydro-3-hydroxy benzofuran -5- formic acid.
By taking 2,5- dibromomethylbenzene as an example, route of the present invention is as follows:
The beneficial effects of the present invention are:
(1) reaction obtains 1- oxo -1,3- dihydro-3-hydroxy benzofuran -5- formic acid with higher yield, after reaction
Reason is simple, and washing, extraction and filtering is only needed just to obtain pure target product；
(2) method therefor synthesizes simple, raw material and is easy to get, and is convenient for large-scale preparation；
(3) selecting method requires instrument and equipment simple, there is very big advantage in reaction cost, good in economic efficiency.
Further, 2,5- halogeno toluene is 2,5- dichlorotoleune or 2,5- dibromomethylbenzene in step (1)；
Organic solvent one is any one of petroleum ether, n-hexane or hexamethylene；
Protection gas is any of nitrogen, argon gas or neon in step (2) and/or step (3)；
Palladium catalyst is palladium chloride, palladium acetate, tetra-triphenylphosphine palladium, [bis- (the diphenylphosphine) -1,1'- dinaphthalenes of 2,2'-] two
Palladium chloride, chlorine (1,5- cyclo-octadiene) methyl palladium (II), bis- (dicyclohexyl amine) acid chlorides (II), three (two benzal-base acetone)
Two palladiums, double focusing chlorination two (2- methylallyl) palladium it is any；
Phosphine ligands be bis- (the diphenylphosphine) -9,9- xanthphos of 4,5-, (bromination triphenyl phosphoniums) bis- to two methylene benzene,
(Lvization triphenyl phosphoniums) bis- to two methylene benzene, two (1- naphthalene) phosphonium chlorides, three (4- aminomethyl phenyl) phosphine oxides or four triphenylphosphines
One of；
Organic solvent two is any mixing mixed with water with the volume ratio of 10:1 in tetrahydrofuran or dimethyl sulfoxide
Solvent；
Alkali is any of trimethylamine, triethylamine or sodium carbonate.
It is that raw material is easy to get using above-mentioned further beneficial effect, the reaction time is short, and post-processing is simple, does not need spy
Different means of purification.
Further, glacial acetic acid, acetic anhydride, the concentrated sulfuric acid and 2 in step (1), the molar ratio of 5- halogeno toluene are 21-25:13-
15:5-8:1；
The molar ratio of chromium trioxide and 2,5- halogeno toluene is 3-5:1；
2,5- dihalo--diacetoxyl methylbenzene, the molar ratio of palladium catalyst and Phosphine ligands in step (2) and/or step (3)
For 1:0.05-0.2:0.1；
The additional amount of organic solvent two is that 20mL organic solvent two is added in every 1g 2,5- dihalo--diacetoxyl methylbenzene；
When alkali is trimethylamine or triethylamine, the volume ratio with water is 1:1, when the alkali is sodium carbonate, the mass ratio with water
For 2:1.
It is further had the beneficial effect that using above-mentioned, reduce the generation of by-product, the reaction time is short, and post-processing is simple, no
Need special means of purification.
Further, step (2) and/or the middle operation for removing organic solvent two of step (3) are as follows: when organic solvent two is tetrahydro
When furans, revolving is added 10 times that water is diluted to original volume after removing organic solvent two；
When organic solvent two is dimethyl sulfoxide, pH value is adjusted to 10-12, to have with highly basic weak solution after being diluted with water
Solvent four is washed three times, wherein highly basic weak solution is the sodium hydroxide or potassium hydroxide solution that concentration is 2mol/L；It is organic molten
Agent four is any one of ethyl acetate, ether, dichloromethane or chloroform.
Detailed description of the invention
Fig. 1 is the nuclear magnetic resonance spectroscopy spectrogram of 2- formoxyl terephthalic acid (TPA) obtained in the embodiment of the present invention 1；
Fig. 2 is the nuclear-magnetism of 1- oxo -1,3- dihydro-3-hydroxy benzofuran -5- formic acid obtained in the embodiment of the present invention 1
The hydrogen that resonates composes spectrogram.
Specific embodiment
Following will be combined with the drawings in the embodiments of the present invention, and technical solution in the embodiment of the present invention carries out clear, complete
Site preparation description, it is clear that described embodiments are only a part of the embodiments of the present invention, instead of all the embodiments.It is based on
Embodiment in the present invention, it is obtained by those of ordinary skill in the art without making creative efforts every other
Embodiment shall fall within the protection scope of the present invention.
In the examples below, bis- (diphenylphosphine) -9,9- xanthphos of 4,5-, to the bis- (brominations three of two methylene benzene
Ben Ji Phosphonium), (Lvization triphenyl phosphoniums) bis- to two methylene benzene, two (1- naphthalene) phosphonium chlorides, three (4- aminomethyl phenyl) phosphine oxides or four
Triphenylphosphine (97%, splendid remote chemical science and technology limited Company)；Palladium chloride, palladium acetate, tetra-triphenylphosphine palladium, 2,2'- bis- (two
Phenylphosphine) -1,1'- dinaphthalene] palladium chloride, chlorine (1,5- cyclo-octadiene) methyl palladium (II), bis- (dicyclohexyl amine) acid chlorides (II),
Three (two benzal-base acetone) two palladiums, double focusing chlorination two (2- methylallyl) palladium (98%, Arkpharm)；2,5- dibromo first
Benzene (70%, EAP Chem company)；Acetic anhydride, chromium trioxide (analyzing pure, Chinese medicines group chemical reagent)；Concentrated sulfuric acid H2SO4(day
Yong great chemical reagent Co., Ltd, Jinshi City)；Glacial acetic acid, Anhydrous potassium carbonate (analyze pure, Tianjin great Mao chemical reagent factory)；Tetrahydro
Furans, petroleum ether, n-hexane, ethyl acetate, methylene chloride, anhydrous sodium sulfate (analyze pure, Tianjin North Star Founder chemical reagent work)；N,
Dinethylformamide (99.5%, analyze pure, Tianjin Yong great chemical reagent Co., Ltd)；Hydrochloric acid HCl (98%, Dongguan City
Qiao Ke Chemical Co., Ltd.)；Anhydrous methanol, triethylamine, sodium hydroxide, sodium chloride, dimethyl sub-maple (analyze pure, Tianjin Shen
Safe chemical reagent Science and Technology Ltd.).
DHG-9070A electric heating constant-temperature blowing drying box (Yuhua Instrument Co., Ltd., Gongyi City)；DF-101S heat collecting type
Magnetic heating stirrer (newly precious instrument produces Jintan City's White Tower)；Rotary evaporator RE-52AA (the sub- flourish biochemical instrument in Shanghai)；SH2-
D (III) circulating water type vacuum pump (Yuhua Instrument Co., Ltd., Gongyi City)；85-1 type magnetic stirring apparatus (Shanghai standing grain vapour instrument
Co., Ltd)；KQ-400KDE type high power numerical control ultrasonic cleaner (Kunshan Ultrasonic Instruments Co., Ltd.)；ZF-7A is portable
Ultraviolet monitoring lamp (Shanghai Baoshan cares for village's electric light instrument plant)；CP214 electronic balance (Ao Haosi Instrument Ltd.).
Embodiment 1
The preparation method of 1- oxo -1,3- dihydro-3-hydroxy benzofuran -5- formic acid, steps are as follows:
(1) by 2,5- dibromomethylbenzene (14.5g, 0.058mol), glacial acetic acid (87.07g, 1.45mol), acetic anhydride
(77.8g, 0.76mol), the concentrated sulfuric acid (30.8g, 0.31mol) sequentially add in the single-necked flask of 250mL, and ice-water bath is by reactant
System is cooled to 0-5 DEG C.It is vigorously stirred down, chromium trioxide (17.5g, 0.175mol) is slowly added portionwise, and adition process is lasting
30min, ice-water bath control reaction temperature at 0-5 DEG C；End reaction liquid is continuing to stir 2h at such a temperature, then at room temperature
Stir 2h.Reaction solution is poured slowly into ice water (850mL), and is quickly stirred, and a large amount of absinthe-green solids is occurred, is put into ultrasound
Wave shakes 20min, filters, obtains light green solid, washed in batches using 200mL deionized water, and obtained solid is sufficiently dry.
Obtained solid is uniformly dispersed with n-hexane, and mixed liquor shakes 1h in ultrasonoscope, is filtered to get white solid 2,5- bis- is bromo-
Diacetoxyl methylbenzene 19.1g, yield 90%.
(2) the bromo- diacetoxyl methylbenzene (3g, 8mmol) of 2,5- bis-, palladium acetate (89.8mg, 0.4mmol) and 4,5- is bis-
(diphenylphosphine) -9,9- xanthphos (463mg, 0.8mmol) are put into twoport flask substitutes gas 3 under nitrogen protection
It is secondary, the tetrahydrofuran (50mL) and deionized water (10mL) for first passing through degassing process in advance, again displacement gas 3 times are then added.With
It evacuates the nitrogen in reactor at room temperature afterwards, until reaction solution is emerged a large amount of bubbles, is re-filled with an oxidation an of atmospheric pressure
Carbon gas is added triethylamine (6mL), and system is substituted gas 3 times again, carbon monoxide atmosphere of the final reaction solution in an atmospheric pressure
In enclosing, oil bath control reacts 20h at 65 DEG C.Vacuum distillation removes tetrahydrofuran warp after reaction, adds after Liquid Residue filtering
Enter water to dilute and adjust pH value to 11, ethyl acetate washs water phase 3 times, and water phase repeated filtration is clear solution, aqueous pH values tune
To 3, a large amount of white solids are precipitated, rapid filtration under suction, and a large amount of deionized waters wash filter cakes, 60 DEG C of vacuum oven dry 10h to get
To the bromo- 3- formylbenzoate 1.48g of 4-, yield 80.7%.
Product nuclear magnetic resonance spectroscopy result are as follows:1HNMR(400MHz,DMSO-d6)δ13.54(br,1H),10.24(s,1H),
8.31 (s, 1H), 8.07 (d, J=8.0Hz, 1H), 7.93 (d, J=8.0Hz, 1H), spectrogram such as Fig. 1.
(3) the bromo- 3- formylbenzoate (1.8g, 8mmol) of 4-, palladium acetate (89.8mg, 0.4mmol) and 4,5- is bis-
(diphenylphosphine) -9,9- xanthphos (463mg, 0.8mmol) are put into twoport flask substitutes gas 3 under nitrogen protection
It is secondary, the tetrahydrofuran (50mL) and deionized water (10mL) for first passing through degassing process in advance, again displacement gas 3 times are then added.With
It evacuates the nitrogen in reactor at room temperature afterwards, until reaction solution is emerged a large amount of bubbles, is re-filled with an oxidation an of atmospheric pressure
Carbon gas is added triethylamine (6mL), and system is substituted gas 3 times again, carbon monoxide atmosphere of the final reaction solution in an atmospheric pressure
In enclosing, oil bath control reacts 6h at 65 DEG C.Vacuum distillation removes tetrahydrofuran warp after reaction, is added after Liquid Residue filtering
Water dilutes and adjusts pH value to 11, and ethyl acetate washs water phase 3 times, and water phase repeated filtration is clear solution, the pH value tune of water phase
To 3, ethyl acetate is extracted three times, and organic phase is dried, filtered with anhydrous sodium sulfate, and revolving obtains target compound 1.4g, yield
90%.
Product nuclear magnetic resonance spectroscopy result are 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), spectrogram such as Fig. 2.
Embodiment 2
The preparation method of 1- oxo -1,3- dihydro-3-hydroxy benzofuran -5- formic acid, steps are as follows:
(1) by 2,5- dichlorotoleune (9.34g, 0.058mol), glacial acetic acid (87.08g, 1.45mol), acetic anhydride
(88.82g, 0.87mol), the concentrated sulfuric acid (46.1g, 0.46mol) sequentially add in the single-necked flask of 250mL, and ice-water bath will react
System is cooled to 0-5 DEG C.It is vigorously stirred down, chromium trioxide (29g, 0.29mol) is slowly added portionwise, and adition process is lasting
30min, ice-water bath control reaction temperature at 0-5 DEG C；End reaction liquid is continuing to stir 2h at such a temperature, then at room temperature
Stirring is for 24 hours.Reaction solution is poured slowly into ice water (1700mL), and is quickly stirred, and a large amount of absinthe-green solids is occurred, is put into super
Sound wave shock 20min is filtered, is obtained light green solid, washed in batches using 200mL deionized water, obtained solid is sufficiently dry
It is dry.Obtained solid is uniformly dispersed with petroleum ether, and mixed liquor shakes 1h in ultrasonoscope, is filtered to get white solid 2,5- bis-
Chlorine diacetoxyl methylbenzene 13.7g, yield 85%.
(2) by the chloro- diacetoxyl methylbenzene (3g, 8mmol) of 2,5- bis-, tetra-triphenylphosphine palladium (462mg, 0.4mmol), right
Two methylene benzene bis- (chlorinated triphenyl base phosphine) (560mg, 0.8mmol) and sodium carbonate (5g) are put into twoport flask under nitrogen protection
It substitutes gas 3 times, the dimethyl sulfoxide (50mL) and deionized water (10mL) for first passing through degassing process in advance is then added, replaces again
Gas 3 times.The nitrogen in reactor is then evacuated at room temperature, is re-filled with the CO gas of an atmospheric pressure, system is taken out again
Ventilation body 3 times, for final reaction solution in the carbon monoxide atmosphere of an atmospheric pressure, oil bath control reacts 4h at 110 DEG C.Instead
500mL water is added after should terminating into reaction solution, is filtered to remove insoluble matter, adjusts pH value to 11, methylene chloride washs water phase 3
Secondary, aqueous pH values are adjusted to 3, and a large amount of white solids are precipitated, rapid filtration under suction, and a large amount of deionized waters wash filter cake, vacuum oven 60
DEG C dry 10h is to get arriving the chloro- 3- formylbenzoate 1.48g of 4-, yield 95%.
(3) by the chloro- 3- formylbenzoate (1.84g, 10mmol) of 4-, tetra-triphenylphosphine palladium (578mg, 0.5mmol), right
Two methylene benzene bis- (chlorinated triphenyl base phosphine) (700mg, 1.0mmol) and sodium carbonate (5g) are put into twoport flask under nitrogen protection
It substitutes gas 3 times, the dimethyl sulfoxide (50mL) and deionized water (10mL) for first passing through degassing process in advance is then added, replaces again
Gas 3 times.The nitrogen in reactor is then evacuated at room temperature, is re-filled with the CO gas of an atmospheric pressure, system is taken out again
Ventilation body 3 times, for final reaction solution in the carbon monoxide atmosphere of an atmospheric pressure, oil bath control reacts 12h at 110 DEG C.
After reaction, reaction solution is poured into 500mL water, repeated filtration removes insoluble substance, filtrate adjusting pH value to 11, methylene chloride
Washing water phase 3 times, water phase repeated filtration are clear solution, and the pH value of water phase is adjusted to 3, and methylene chloride extracts three times, and organic phase is used
Anhydrous sodium sulfate dries, filters, and revolving obtains target compound 1.6g, yield 82%.
Product nuclear magnetic resonance spectroscopy result are 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).
Embodiment 3
The preparation method of 1- oxo -1,3- dihydro-3-hydroxy benzofuran -5- formic acid, steps are as follows:
(1) with 1 step of embodiment (1) the difference is that chromium trioxide dosage is 23.2g, 0.232mol, gained is solid
Body is uniformly dispersed with petroleum ether, and mixed liquor shakes 1h in ultrasonoscope, is filtered to get white solid 2, the bromo- oxalic acid of 5- bis-
Ylmethyl benzene 19.3g, yield 91%.
(2) with 1 step of embodiment (2) the difference is that palladium reagent is palladium chloride (71mg, 0.4mmol), Phosphine ligands
For four triphenylphosphines (463mg, 0.8mmol), alkali is trimethylamine (6mL), and reaction time 4h obtains 2- formoxyl terephthaldehyde
Sour 1.28g, yield 82%.
(3) with 1 step of embodiment (3) the difference is that palladium reagent is that [bis- (the diphenylphosphine) -1,1'- of 2,2'- join
Naphthalene] palladium chloride (320mg, 0.4mmol), Phosphine ligands are that two (1- naphthalene) phosphonium chlorides (257mg, 0.8mmol) are anti-at 65 DEG C
Answer 16h.Obtain target compound 1.1g, yield 71%.
Product nuclear magnetic resonance spectroscopy result are 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).
Embodiment 4
The preparation method of 1- oxo -1,3- dihydro-3-hydroxy benzofuran -5- formic acid, steps are as follows:
(1) identical with 1 step of embodiment (1).
(2) with 1 step of embodiment (2) the difference is that palladium reagent tetra-triphenylphosphine palladium (462mg, 0.4mmol), phosphine
Ligand is four triphenylphosphines (463mg, 0.8mmol), and reaction time 1.5h obtains 2- formoxyl terephthalic acid (TPA) 1.3g, is received
Rate 83%.
(3) with 1 step of embodiment (3) the difference is that palladium reagent is three (two benzal-base acetone) two palladiums
(286mg, 0.4mmol), Phosphine ligands are that three (4- aminomethyl phenyl) phosphine oxides (257mg, 0.8mmol) react 16h at 65 DEG C.
To target compound 1.33g, yield 86%.
Product nuclear magnetic resonance spectroscopy result are 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).
Embodiment 5
The preparation method of 1- oxo -1,3- dihydro-3-hydroxy benzofuran -5- formic acid, steps are as follows:
(1) identical with 1 step of embodiment (1).
(2) with 1 step of embodiment (2) the difference is that palladium reagent chlorine (1,5- cyclo-octadiene) methyl palladium (106mg,
0.4mmol), Phosphine ligands are (bromination triphenyl phosphonium) (631mg, 0.8mmol) bis- to two methylene benzene, and reaction time 3h is obtained
2- formoxyl terephthalic acid (TPA) 1.26g, yield 81%.
(3) with 1 step of embodiment (3) the difference is that palladium reagent be bis- (dicyclohexyl amine) acid chlorides (234mg,
0.4mmol), Phosphine ligands are that two (1- naphthalene) phosphonium chlorides (257mg, 0.8mmol) react 16h at 65 DEG C.Obtain target chemical combination
Object 1.13g, yield 73%.
Product nuclear magnetic resonance spectroscopy result are 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 (10)
1. a kind of method of synthesis 1- oxo -1,3- dihydro-3-hydroxy benzofuran -5- formic acid, which is characterized in that including as follows
Step:
(1) it takes 2,5- halogeno toluene to be added into the mixed liquor of glacial acetic acid, acetic anhydride and the concentrated sulfuric acid, it is anti-that chromium trioxide oxidation is added
Answer, obtain reaction solution, reaction solution is added and is stirred into ice water to there is light green precipitating, ultrasonic vibration, filter and spend from
Sub- water washing, the light green solid after being dried are dissolved with organic solvent one, are filtered after ultrasonic vibration, are obtained 2,5- dihalo--
Diacetoxyl methylbenzene；
(2) by 2,5- dihalo--diacetoxyl methylbenzene protection gas protection under with palladium catalyst, Phosphine ligands, organic solvent two,
Water and alkali mixing, are reacted under carbon monoxide environment, remove organic solvent two after reaction, are adjusted pH value to 1-4, are taken out
Filter, is washed with deionized water, is dried to obtain 4- halogen -3- formylbenzoate；
(3) by 4- halogen -3- formylbenzoate protection gas protection under with palladium catalyst, Phosphine ligands, organic solvent two, water and
Alkali mixing, is reacted under carbon monoxide environment, removes organic solvent two after reaction, and adjusting pH value to 1-4 filters,
1- oxo -1,3- dihydro-3-hydroxy benzofuran -5- formic acid is obtained by extraction by organic solvent three after washing with deionized water.
2. a kind of preparation method of 1- oxo -1,3- dihydro-3-hydroxy benzofuran -5- formic acid according to claim 1,
It is characterized in that, glacial acetic acid described in step (1), acetic anhydride, the concentrated sulfuric acid and 2, the molar ratio of 5- halogeno toluene is 21-25:13-
15:5-8:1；
The molar ratio of the chromium trioxide and 2,5- halogeno toluene is 3-5:1；
The mass ratio of the reaction solution and ice water is 1:5.
3. a kind of side for synthesizing 1- oxo -1,3- dihydro-3-hydroxy benzofuran -5- formic acid according to claim 1 or 2
Method, which is characterized in that 2,5- halogeno toluene described in step (1) is 2,5- dichlorotoleune or 2,5- dibromomethylbenzene；
The organic solvent one is any one of petroleum ether, n-hexane or hexamethylene.
4. a kind of method of synthesis 1- oxo -1,3- dihydro-3-hydroxy benzofuran -5- formic acid according to claim 1,
It is characterized in that, the temperature of mixed liquor is 0-5 DEG C when chromium trioxide being added in the step (1)；
The oxidizing reaction temperature is 23-25 DEG C, time 2-24h.
5. a kind of method of synthesis 1- oxo -1,3- dihydro-3-hydroxy benzofuran -5- formic acid according to claim 1,
It is characterized in that, protection gas described in step (2) and/or step (3) is any of nitrogen, argon gas or neon；
The palladium catalyst is palladium chloride, palladium acetate, tetra-triphenylphosphine palladium, bis- (the diphenylphosphine) -1,1'- dinaphthalenes of 2,2'-] dichloro
Change palladium, chlorine (1,5- cyclo-octadiene) methyl palladium (II), bis- (dicyclohexyl amine) acid chlorides (II), three (two benzal-base acetone) two
Palladium, double focusing chlorination two (2- methylallyl) palladium it is any；
The Phosphine ligands be bis- (the diphenylphosphine) -9,9- xanthphos of 4,5-, (bromination triphenyl phosphoniums) bis- to two methylene benzene,
(Lvization triphenyl phosphoniums) bis- to two methylene benzene, two (1- naphthalene) phosphonium chlorides, three (4- aminomethyl phenyl) phosphine oxides or four triphenylphosphines
One of；
The organic solvent two is any mixing mixed with water with the volume ratio of 10:1 in tetrahydrofuran or dimethyl sulfoxide
Solvent；
The alkali is any of trimethylamine, triethylamine or sodium carbonate.
6. a kind of method of synthesis 1- oxo -1,3- dihydro-3-hydroxy benzofuran -5- formic acid according to claim 5,
It is characterized in that, 2,5- dihalo--diacetoxyl methylbenzene, palladium catalyst and Phosphine ligands described in step (2) and/or step (3)
Molar ratio be 1:0.05:0.1；
The additional amount of the organic solvent two is that 20mL organic solvent two is added in every 1g 2,5- dihalo--diacetoxyl methylbenzene；
When the alkali is trimethylamine or triethylamine, the volume ratio with water is 1:1, when the alkali is sodium carbonate, the mass ratio with water
For 1:2.
7. a kind of side for synthesizing 1- oxo -1,3- dihydro-3-hydroxy benzofuran -5- formic acid according to claim 5 or 6
Method, which is characterized in that in the step (2) and/or step (3), carbon monoxide environment is by being filled with carbon monoxide gas after evacuating
Body 5min is obtained；
The reaction temperature is 65-110 DEG C, reaction time 1.5-4h, and in reaction process, every 30min is filled with one time one oxidation
Carbon gas 5min；
The operation for adjusting pH value to 1-4 is the salt acid for adjusting pH value with 10% to 1-4.
8. a kind of method of synthesis 1- oxo -1,3- dihydro-3-hydroxy benzofuran -5- formic acid according to claim 7,
It is characterized in that, removing the operation of organic solvent two in step (2) and/or step (3) are as follows: when organic solvent two is tetrahydrofuran
When, revolving is added 10 times that water is diluted to raw water volume after removing organic solvent two；
When organic solvent two is dimethyl sulfoxide, pH value is adjusted to 10-12, with organic molten with highly basic weak solution after being diluted with water
Agent four is washed three times.
9. a kind of preparation method of 1- oxo -1,3- dihydro-3-hydroxy benzofuran -5- formic acid according to claim 8,
It is characterized in that, the highly basic weak solution is the sodium hydroxide or potassium hydroxide solution that concentration is 2mol/L；
The organic solvent four is any one of ethyl acetate, ether, dichloromethane or chloroform.
10. a kind of preparation side of 1- oxo -1,3- dihydro-3-hydroxy benzofuran -5- formic acid according to claim 1
Method, which is characterized in that dry operation described in step (2) is 60 DEG C of dry 8-12h；
Organic solvent three described in step (3) is ethyl acetate or methylene chloride.
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| CN111234249A (en) * | 2020-02-17 | 2020-06-05 | 忻州师范学院 | Aliphatic tertiary amine functionalized chromium-based metal organic framework material and preparation method thereof |
| CN111303440A (en) * | 2020-02-17 | 2020-06-19 | 忻州师范学院 | Aliphatic tertiary amine functional zirconium-based metal organic framework material and preparation method thereof |
| CN111303440B (en) * | 2020-02-17 | 2021-11-19 | 忻州师范学院 | Aliphatic tertiary amine functional zirconium-based metal organic framework material and preparation method thereof |
| CN111234249B (en) * | 2020-02-17 | 2021-11-19 | 忻州师范学院 | Aliphatic tertiary amine functionalized chromium-based metal organic framework material and preparation method thereof |
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