CN114573535B - Preparation method of chemical intermediate 3-hydroxyphthalic anhydride - Google Patents
Preparation method of chemical intermediate 3-hydroxyphthalic anhydride Download PDFInfo
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- CCTOEAMRIIXGDJ-UHFFFAOYSA-N 4-hydroxy-2-benzofuran-1,3-dione Chemical compound OC1=CC=CC2=C1C(=O)OC2=O CCTOEAMRIIXGDJ-UHFFFAOYSA-N 0.000 title claims abstract description 37
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- 239000000126 substance Substances 0.000 title claims abstract description 15
- MNUOZFHYBCRUOD-UHFFFAOYSA-N 3-hydroxyphthalic acid Chemical compound OC(=O)C1=CC=CC(O)=C1C(O)=O MNUOZFHYBCRUOD-UHFFFAOYSA-N 0.000 claims abstract description 50
- 238000006243 chemical reaction Methods 0.000 claims abstract description 37
- 238000000034 method Methods 0.000 claims abstract description 20
- 239000003054 catalyst Substances 0.000 claims abstract description 15
- 238000006297 dehydration reaction Methods 0.000 claims abstract description 12
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims abstract description 10
- FRASJONUBLZVQX-UHFFFAOYSA-N 1,4-dioxonaphthalene Natural products C1=CC=C2C(=O)C=CC(=O)C2=C1 FRASJONUBLZVQX-UHFFFAOYSA-N 0.000 claims abstract description 9
- BOKGTLAJQHTOKE-UHFFFAOYSA-N 1,5-dihydroxynaphthalene Chemical compound C1=CC=C2C(O)=CC=CC2=C1O BOKGTLAJQHTOKE-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000005708 Sodium hypochlorite Substances 0.000 claims abstract description 9
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 claims abstract description 9
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000010949 copper Substances 0.000 claims abstract description 7
- 229910052802 copper Inorganic materials 0.000 claims abstract description 7
- 239000003444 phase transfer catalyst Substances 0.000 claims abstract description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- 239000007787 solid Substances 0.000 claims description 10
- 239000000243 solution Substances 0.000 claims description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 8
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- 239000003960 organic solvent Substances 0.000 claims description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 6
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 claims description 6
- 238000001035 drying Methods 0.000 claims description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 6
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 6
- 239000000047 product Substances 0.000 claims description 6
- 229960001701 chloroform Drugs 0.000 claims description 5
- 239000010410 layer Substances 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 239000012044 organic layer Substances 0.000 claims description 5
- 238000010992 reflux Methods 0.000 claims description 5
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 4
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 claims description 4
- 230000018044 dehydration Effects 0.000 claims description 4
- 238000001914 filtration Methods 0.000 claims description 4
- 238000000746 purification Methods 0.000 claims description 4
- 238000005406 washing Methods 0.000 claims description 4
- 229910021589 Copper(I) bromide Inorganic materials 0.000 claims description 3
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 3
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 3
- SUAKHGWARZSWIH-UHFFFAOYSA-N N,N‐diethylformamide Chemical compound CCN(CC)C=O SUAKHGWARZSWIH-UHFFFAOYSA-N 0.000 claims description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 3
- 239000012320 chlorinating reagent Substances 0.000 claims description 3
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 3
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 claims description 3
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims description 3
- 229940045803 cuprous chloride Drugs 0.000 claims description 3
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 claims description 3
- 239000007864 aqueous solution Substances 0.000 claims description 2
- 238000001816 cooling Methods 0.000 claims description 2
- 229940076286 cupric acetate Drugs 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 230000020477 pH reduction Effects 0.000 claims description 2
- 239000002244 precipitate Substances 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 230000001105 regulatory effect Effects 0.000 claims description 2
- 238000000926 separation method Methods 0.000 claims description 2
- 238000003756 stirring Methods 0.000 claims description 2
- 239000002994 raw material Substances 0.000 abstract description 8
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 6
- 238000007254 oxidation reaction Methods 0.000 abstract description 4
- 230000008569 process Effects 0.000 abstract description 4
- 239000012847 fine chemical Substances 0.000 abstract description 3
- 238000007867 post-reaction treatment Methods 0.000 abstract description 3
- 230000009471 action Effects 0.000 abstract description 2
- 238000005516 engineering process Methods 0.000 abstract description 2
- 150000007530 organic bases Chemical class 0.000 abstract description 2
- 238000003889 chemical engineering Methods 0.000 abstract 1
- 239000000203 mixture Substances 0.000 description 9
- 239000000543 intermediate Substances 0.000 description 5
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
- 238000003912 environmental pollution Methods 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000006193 diazotization reaction Methods 0.000 description 3
- 238000001308 synthesis method Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000006555 catalytic reaction Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000012286 potassium permanganate Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 238000002061 vacuum sublimation Methods 0.000 description 2
- 239000002351 wastewater Substances 0.000 description 2
- BLMBNEVGYRXFNA-UHFFFAOYSA-N 1-methoxy-2,3-dimethylbenzene Chemical compound COC1=CC=CC(C)=C1C BLMBNEVGYRXFNA-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- DULQZGQVLHMCAU-UHFFFAOYSA-N 3-methoxyphthalic acid Chemical compound COC1=CC=CC(C(O)=O)=C1C(O)=O DULQZGQVLHMCAU-UHFFFAOYSA-N 0.000 description 1
- ROFZMKDROVBLNY-UHFFFAOYSA-N 4-nitro-2-benzofuran-1,3-dione Chemical compound [O-][N+](=O)C1=CC=CC2=C1C(=O)OC2=O ROFZMKDROVBLNY-UHFFFAOYSA-N 0.000 description 1
- 241000711573 Coronaviridae Species 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 150000001879 copper Chemical class 0.000 description 1
- 230000017858 demethylation Effects 0.000 description 1
- 238000010520 demethylation reaction Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000005582 sexual transmission Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- 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
- C07D307/89—Benzo [c] furans; Hydrogenated benzo [c] furans with two oxygen atoms directly attached in positions 1 and 3
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J27/00—Catalysts comprising the elements or compounds of halogens, sulfur, selenium, tellurium, phosphorus or nitrogen; Catalysts comprising carbon compounds
- B01J27/06—Halogens; Compounds thereof
- B01J27/08—Halides
- B01J27/122—Halides of copper
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
- B01J31/0235—Nitrogen containing compounds
- B01J31/0239—Quaternary ammonium compounds
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J35/00—Catalysts, in general, characterised by their form or physical properties
- B01J35/19—Catalysts containing parts with different compositions
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Catalysts (AREA)
Abstract
The invention discloses a preparation method of a chemical intermediate 3-hydroxyphthalic anhydride, and belongs to the field of fine chemical engineering. The invention adopts cheap 1, 5-dihydroxynaphthalene as raw material, uses sodium hypochlorite to carry out oxidation reaction under the combined action of phase transfer catalyst and copper catalyst to generate 3-hydroxyphthalic acid, and uses organic base to catalyze and carry out dehydration reaction with chloridizing reagent such as thionyl chloride to generate 3-hydroxyphthalic anhydride. The 3-hydroxy phthalic anhydride prepared by the method has high yield and good purity, avoids using high-risk reagents and national easily-made tubular chemicals, has mild reaction process conditions, is economical, simple, convenient and safe in post-reaction treatment, and can be industrially produced by the process technology.
Description
Technical Field
The invention belongs to the field of fine chemical preparation, and particularly relates to a preparation method of chemical intermediate 3-hydroxyphthalic anhydride.
Background
The 3-hydroxy phthalic anhydride has wide application, and is a fine chemical intermediate of medicines, pesticides, photosensitive materials and the like. The product can be used for developing modified human serum albumin, has high bactericidal power, can prevent sexual transmission of HIV, can produce new coronavirus drugs with strong transmission inhibition and low sensitivity of neutralizing antibodies, can be used as intermediates, resins and the like of high-efficiency paddy field herbicides, and has wide market application prospect. At present, the methods for synthesizing 3-hydroxyphthalic anhydride are disclosed and reported in domestic and foreign documents, and mainly comprise the following synthetic methods.
Synthesis method one (see fig. 1): 3-nitrophthalic anhydride is taken as a raw material, and is subjected to hydrogenation reduction and diazotization to obtain 3-hydroxyphthalic anhydride [ Journal of the American Chemical Society,1955,77,5092]. The reaction has the problems of large amount of wastewater, low yield, serious environmental pollution and the like, and does not accord with national industrial policies and environmental protection laws and regulations in China.
The synthesis method II (see figure 2) takes 3-nitrobenzodinitrile as a raw material, and 3-hydroxyphthalic anhydride is obtained through diazotization, base catalytic hydrolysis and vacuum sublimation reaction, the detailed description is shown in Chinese patent No. 104910133, a large amount of toxic wastewater is generated in the diazotization and hydrolysis process, the vacuum sublimation engineering reaction is complex, and the method is suitable for small-batch synthesis research in a synthesis laboratory and is difficult to realize industrial production.
The synthesis process includes the first step of producing 3-hydroxy phthalic acid with 3-halogeno phthalate as material and strong alkali under the catalysis of copper salt and high temperature condition, and the subsequent dewatering condensation of acetic anhydride under the catalysis of organic base to obtain 3-hydroxy phthalic anhydride. The method has simple reaction steps, but has higher raw material price, difficult catalyst recovery and higher production cost when realizing industrialization.
The synthesis method IV (see figure 4) is reported in Chinese patent No. CN10718187, and the method adopts 1-methoxy-2, 3-dimethylbenzene as a raw material and generates 3-methoxy phthalic acid by oxidation of potassium permanganate. And then the 3-hydroxy phthalic anhydride is prepared by the reactions such as boron tribromide demethylation, dehydration and the like, and a large amount of oxidizing agent potassium permanganate and expensive boron tribromide are used in the reaction, so that the reaction yield is unstable, the environmental pollution is serious, and the related requirements of the current environmental protection policy in China are not met.
Therefore, the preparation method for synthesizing the 3-hydroxyphthalic anhydride has the advantages of mild reaction conditions, simple and convenient operation, capability of effectively avoiding the use of high-risk reagents and national control chemicals, low environmental pollution, high yield and low cost.
Disclosure of Invention
Aiming at the problems of complex operation, serious environmental pollution, low yield and the like in the prior art for preparing 3-hydroxyphthalic anhydride, the invention provides a method for preparing 3-hydroxyphthalic anhydride by using 1, 5-dihydroxynaphthalene with low price as a raw material, carrying out oxidation reaction by using sodium hypochlorite under the combined action of a phase transfer catalyst and a copper catalyst to generate 3-hydroxyphthalic acid, and then carrying out dehydration to generate 3-hydroxyphthalic anhydride. The 3-hydroxy phthalic anhydride prepared by the method has high yield and good purity, avoids using high-risk reagents and national easily-made tubular chemicals, has mild reaction process conditions, is economical, simple, convenient and safe in post-reaction treatment, and can be industrially produced by the process technology.
In order to achieve the purpose of the invention, the technical scheme adopted is as follows:
the preparation method of the chemical intermediate 3-hydroxyphthalic anhydride comprises the following steps: adding 1, 5-dihydroxynaphthalene and an organic solvent, adding a phase transfer catalyst, a copper catalyst and a sodium hypochlorite aqueous solution under stirring, obtaining 3-hydroxyphthalic acid after the reaction at room temperature is finished, and obtaining 3-hydroxyphthalic anhydride after dehydration reaction.
Further, the reaction time for preparing the 3-hydroxyphthalic acid is 2-4 hours.
Further, after the preparation reaction of the 3-hydroxyphthalic acid is finished, the method further comprises the steps of separation and purification: separating out an organic layer, acidifying an aqueous layer by using acid, regulating the pH value to 2+/-0.5, separating out a precipitate, filtering, washing with water, and drying to obtain an off-white solid 3-hydroxyphthalic acid.
Further, the acid for acidification is any one of hydrochloric acid, sulfuric acid and phosphoric acid.
Further, the organic solution in the preparation of the 3-hydroxyphthalic acid is any one or more of dichloroethane, dichloromethane and trichloromethane.
Further, the copper catalyst in the preparation of the 3-hydroxyphthalic acid is any one or more of cuprous iodide, cuprous chloride, cuprous bromide and cupric acetate.
Further, the phase transfer catalyst in the preparation of the 3-hydroxyphthalic acid is any one of tetrabutylammonium bromide, tetrabutylammonium chloride and benzyl triethylammonium chloride.
Further, the dehydration method comprises the following steps: adding the prepared 3-hydroxyphthalic acid, organic solution and catalyst into a reaction bottle, cooling to 0-5 ℃, dropwise adding a chlorinating reagent (such as thionyl chloride, phosphorus oxychloride and the like) to react for 15-45 minutes at 0-20 ℃, heating and raising the temperature, reacting for 1-3 hours under the condition of reflux, recovering the organic solvent under reduced pressure after the reaction is finished, and drying the product to obtain white solid 3-hydroxyphthalic anhydride.
Further, the organic solution in the dehydration reaction is cyclohexane, n-hexane, n-heptane, acetonitrile, or the like.
Further, the catalyst in the dehydration reaction is any one or more of N, N-dimethylformamide, N-dimethylacetamide and N, N-diethylformamide.
The invention has the advantages that:
1. the invention takes 1, 5-dihydroxynaphthalene with low price as an initial raw material, uses sodium hypochlorite to carry out oxidation reaction to prepare 3-hydroxy phthalic acid, and then dehydrates and contracts to obtain 3-hydroxy phthalic anhydride, thus the raw material cost is low, high-risk reagents and tubular reagents are avoided, and the preparation process is not limited.
2. The invention improves the reaction yield and reduces the production cost through the combined cooperation of the phase transfer catalyst and the copper catalyst.
3. The method has mild reaction process conditions, and the post-reaction treatment is economical, simple, convenient and safe.
Drawings
FIG. 1 is a scheme for preparing 3-hydroxyphthalic anhydride in the prior art.
FIG. 2 is a scheme for preparing another 3-hydroxyphthalic anhydride of the prior art.
FIG. 3 is a flow chart of another prior art process for preparing 3-hydroxyphthalic anhydride.
FIG. 4 is a scheme for preparing a 3-hydroxyphthalic anhydride according to another prior art.
FIG. 5 shows a process for preparing 3-hydroxyphthalic anhydride of the present invention.
Detailed Description
The present invention is not limited to the following embodiments, and those skilled in the art can implement the present invention in various other embodiments according to the present invention, or simply change or modify the design structure and thought of the present invention, which fall within the protection scope of the present invention. It should be noted that, without conflict, the embodiments of the present invention and features of the embodiments may be combined with each other.
The invention is further described in detail below in connection with the examples:
example 1:
1, 5-dihydroxynaphthalene (8.0 g,50.0 mmol), dichloroethane (80 ml), tetrabutylammonium bromide (0.81 g,2.5 mmol), cuprous iodide (0.95 g,5.0 mmol), and 10% aqueous sodium hypochlorite solution (48 ml,64.0 mmol) were added dropwise, reacted at room temperature for 2 hours, after the reaction was completed, the organic layer dichloroethane was separated, the aqueous layer was acidified with dilute sulfuric acid, the pH was adjusted to 2.+ -. 0.5, precipitation, filtration, water washing, purification and drying to obtain an off-white solid 3-hydroxyphthalic acid (7.6 g, content: 98.1 percent) and the yield is 81.9 percent, 1 H NMR(400MHz,CDCl 3 )d 7.08(m,2H),7.46(dd,J＝8.4,7.7Hz,1H)。
3-Hydroxyphthalic acid (7.6 g,41.0 mmol), cyclohexane (50 mL) and catalyst N, N-dimethylformamide (0.2 mL) were added into a reaction flask, the mixture was cooled to 5℃with an ice bath, thionyl chloride (5.9 g,50.0 mmol) was added dropwise, the mixture was stirred at 10℃for 30 minutes, the mixture was heated and warmed, the reaction was carried out under reflux for 2 hours, after the completion of the reaction, cyclohexane as an organic solvent was recovered under reduced pressure, and the product was purified and dried to give 3-hydroxyphthalic anhydride (5.8 g, 98.2% content) as a white solid, with a yield of 84.8%.
1 H-NMR(500MHz,DMSO-D 6 )δ11.77(s,1H),7.81(dd,J＝8.8,7.3Hz,1H),7.46(dd,J＝7.3,0.8Hz,1H),7.33(dd,J＝8.8,0.8Hz,1H)； 13 C-NMR(100MHz,DMSO-D 6 )δ163.4,161.2,157.1,138.2,132.7,124.1,116.2,114.6。
Example 2
1, 5-dihydroxynaphthalene (8.0 g,50.0 mmol), chloroform (120 ml), tetrabutylammonium chloride (0.42 g,1.5 mmol), cuprous chloride (1.0 g,10.0 mmol) and 12% aqueous sodium hypochlorite solution (50 ml,80.0 mmol) were added dropwise, the reaction was carried out at room temperature for 4 hours, after the reaction was completed, chloroform was separated as an organic layer, the aqueous layer was acidified with hydrochloric acid, the pH was adjusted to 2.+ -. 0.5, precipitation, filtration, water washing, purification and drying were carried out to obtain an off-white solid 3-hydroxyphthalic acid (7.0 g, content: 98.5%) and a yield of 75.6%.
3-Hydroxyphthalic acid (7.0 g,37.9 mmol), N-hexane (60 mL) and catalyst N, N-dimethylacetamide (0.4 mL) were added into a reaction flask, the mixture was cooled to 0℃with an ice bath, thionyl chloride (5.0 g,42.0 mmol) was added dropwise, the mixture was stirred at 10℃for 15 minutes, the mixture was heated and warmed up, the reaction was carried out under reflux for 4 hours, after the reaction was completed, the organic solvent N-hexane was recovered under reduced pressure, and the product was purified and dried to obtain 3-hydroxyphthalic anhydride (5.0 g, 98.6% content) as a white solid, the yield was 79.3%.
Example 3
1, 5-dihydroxynaphthalene (8.0 g,50.0 mmol), methylene chloride (100 ml), benzyl triethylammonium chloride (1.14 g,5.0 mmol), cuprous bromide (1.43 g,10 mmol) and a 10% aqueous sodium hypochlorite solution (60 ml,80.0 mmol) were added dropwise, reacted at room temperature for 3 hours, after the reaction was completed, methylene chloride was separated as an organic layer, and the aqueous layer was acidified with phosphoric acid, and the pH was adjusted to 2.+ -. 0.5, precipitated, filtered, washed with water, purified and dried to obtain an off-white solid 3-hydroxyphthalic acid (7.8 g, content: 98.4%) and a yield of 84.3%.
3-Hydroxyphthalic acid (7.8 g,42.2 mmol), N-heptane (80 mL) and catalyst N, N-diethylformamide (0.3 mL) are added into a reaction bottle, the mixture is cooled to 5 ℃ by an ice bath, phosphorus oxychloride (10.0 g,65.2 mmol) is dropwise added, the mixture is stirred at 5 ℃ for reaction for 20 minutes, the mixture is heated and warmed, the reaction is carried out under reflux condition for 1 hour, after the reaction is finished, the organic solvent N-heptane is recovered under reduced pressure, and the product is purified and dried to obtain white solid 3-hydroxyphthalic anhydride (6.0 g, content 97.7) with the yield of 84.7 percent.
Comparative example 1
1, 5-dihydroxynaphthalene (8.0 g,50.0 mmol), chloroform (120 ml), tetrabutylammonium chloride (0.42 g,1.5 mmol) and 12% aqueous sodium hypochlorite solution (50 ml,80.0 mmol) were added dropwise to the reaction flask, and the reaction was carried out at room temperature, followed by TLC, without reaction.
The foregoing is only a preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art, who is within the scope of the present invention, should make equivalent substitutions or modifications according to the technical scheme and the concept of the present invention, and should be covered by the scope of the present invention.
Claims (6)
1. A preparation method of a chemical intermediate 3-hydroxyphthalic anhydride is characterized by comprising the following steps: the method comprises the following steps: adding 1, 5-dihydroxynaphthalene and an organic solvent, adding a phase transfer catalyst, a copper catalyst and a sodium hypochlorite aqueous solution under stirring, obtaining 3-hydroxyphthalic acid after the reaction at room temperature is finished, and obtaining 3-hydroxyphthalic anhydride after dehydration reaction;
the preparation reaction time of the 3-hydroxyphthalic acid is 2-4 hours;
the copper catalyst is any one or more of cuprous iodide, cuprous chloride, cuprous bromide and cupric acetate;
the dehydration method comprises the following steps: adding the prepared 3-hydroxyphthalic acid, organic solution and catalyst into a reaction bottle, cooling to 0-5 ℃, dropwise adding a chlorinating reagent to react for 15-45 minutes at 0-20 ℃, heating, reacting for 1-3 hours under reflux, recovering the organic solvent under reduced pressure after the reaction is finished, and drying the product to obtain white solid 3-hydroxyphthalic anhydride;
the catalyst in the dehydration reaction is one or more of N, N-dimethylformamide, N-dimethylacetamide and N, N-diethylformamide;
the chlorinating reagent in the dehydration reaction is thionyl chloride and/or phosphorus oxychloride.
2. The method for preparing the chemical intermediate 3-hydroxyphthalic anhydride according to claim 1, characterized in that: the preparation reaction of the 3-hydroxy phthalic acid also comprises the steps of separation and purification after finishing: separating out an organic layer, acidifying an aqueous layer by using acid, regulating the pH value to 2+/-0.5, separating out a precipitate, filtering, washing with water, and drying to obtain an off-white solid 3-hydroxyphthalic acid.
3. The process for preparing 3-hydroxyphthalic anhydride, a chemical intermediate according to claim 2, characterized in that: the acid for acidification is any one of hydrochloric acid, sulfuric acid and phosphoric acid.
4. The method for preparing the chemical intermediate 3-hydroxyphthalic anhydride according to claim 1, characterized in that: the organic solution in the preparation of the 3-hydroxyphthalic acid is any one or more of dichloroethane, dichloromethane and trichloromethane.
5. The method for preparing the chemical intermediate 3-hydroxyphthalic anhydride according to claim 1, characterized in that: the phase transfer catalyst in the preparation of the 3-hydroxy phthalic acid is any one of tetrabutylammonium bromide, tetrabutylammonium chloride and benzyl triethyl ammonium chloride.
6. The method for preparing the chemical intermediate 3-hydroxyphthalic anhydride according to claim 1, characterized in that: the organic solution in the dehydration reaction is cyclohexane, n-hexane, n-heptane or acetonitrile.
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| WO2015067494A1 (en) * | 2013-11-08 | 2015-05-14 | Basf Se | Process for providing dihalogen substituted salicylic acid derivatives |
| CN107118187A (en) * | 2017-06-27 | 2017-09-01 | 济南轩鸿生物医药有限公司 | A kind of preparation method of 3 hydroxyl phthalic anhydride |
| CN108727319A (en) * | 2018-09-05 | 2018-11-02 | 常州大学 | A kind of preparation method of 3- nitrophthalic acids acid anhydride |
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| WO2015067494A1 (en) * | 2013-11-08 | 2015-05-14 | Basf Se | Process for providing dihalogen substituted salicylic acid derivatives |
| CN107118187A (en) * | 2017-06-27 | 2017-09-01 | 济南轩鸿生物医药有限公司 | A kind of preparation method of 3 hydroxyl phthalic anhydride |
| CN108727319A (en) * | 2018-09-05 | 2018-11-02 | 常州大学 | A kind of preparation method of 3- nitrophthalic acids acid anhydride |
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