CN116041295A - Preparation method of 3-bromophthalide - Google Patents
Preparation method of 3-bromophthalide Download PDFInfo
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- CN116041295A CN116041295A CN202310331616.6A CN202310331616A CN116041295A CN 116041295 A CN116041295 A CN 116041295A CN 202310331616 A CN202310331616 A CN 202310331616A CN 116041295 A CN116041295 A CN 116041295A
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- bromophthalide
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- CLMSHAWYULIVFQ-UHFFFAOYSA-N 3-bromo-3h-2-benzofuran-1-one Chemical compound C1=CC=C2C(Br)OC(=O)C2=C1 CLMSHAWYULIVFQ-UHFFFAOYSA-N 0.000 title claims abstract description 82
- 238000002360 preparation method Methods 0.000 title claims abstract description 25
- 238000000034 method Methods 0.000 claims abstract description 24
- 238000007670 refining Methods 0.000 claims abstract description 22
- 238000006243 chemical reaction Methods 0.000 claims abstract description 18
- 238000004519 manufacturing process Methods 0.000 claims abstract description 10
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 5
- WNZQDUSMALZDQF-UHFFFAOYSA-N 2-benzofuran-1(3H)-one Chemical compound C1=CC=C2C(=O)OCC2=C1 WNZQDUSMALZDQF-UHFFFAOYSA-N 0.000 claims description 52
- 238000003756 stirring Methods 0.000 claims description 44
- 239000003054 catalyst Substances 0.000 claims description 40
- 239000008367 deionised water Substances 0.000 claims description 40
- 229910021641 deionized water Inorganic materials 0.000 claims description 40
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 40
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 30
- 238000010438 heat treatment Methods 0.000 claims description 29
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 24
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 24
- 229910052794 bromium Inorganic materials 0.000 claims description 24
- 230000015572 biosynthetic process Effects 0.000 claims description 19
- 238000001816 cooling Methods 0.000 claims description 19
- 238000003786 synthesis reaction Methods 0.000 claims description 19
- 239000000440 bentonite Substances 0.000 claims description 16
- 229910000278 bentonite Inorganic materials 0.000 claims description 16
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 claims description 16
- 239000005543 nano-size silicon particle Substances 0.000 claims description 15
- 235000012239 silicon dioxide Nutrition 0.000 claims description 15
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims description 14
- 239000004327 boric acid Substances 0.000 claims description 14
- 239000012043 crude product Substances 0.000 claims description 14
- 238000000498 ball milling Methods 0.000 claims description 13
- SXTLQDJHRPXDSB-UHFFFAOYSA-N copper;dinitrate;trihydrate Chemical compound O.O.O.[Cu+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O SXTLQDJHRPXDSB-UHFFFAOYSA-N 0.000 claims description 13
- 238000001914 filtration Methods 0.000 claims description 13
- 238000001035 drying Methods 0.000 claims description 11
- 239000002245 particle Substances 0.000 claims description 11
- 239000006087 Silane Coupling Agent Substances 0.000 claims description 10
- 239000013078 crystal Substances 0.000 claims description 10
- 239000007787 solid Substances 0.000 claims description 10
- 239000012798 spherical particle Substances 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 5
- 239000012299 nitrogen atmosphere Substances 0.000 claims description 5
- 238000004321 preservation Methods 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- 238000005470 impregnation Methods 0.000 claims 3
- 238000007781 pre-processing Methods 0.000 claims 1
- 150000002576 ketones Chemical class 0.000 abstract description 10
- 239000003960 organic solvent Substances 0.000 abstract description 10
- 230000008569 process Effects 0.000 abstract description 9
- 238000003912 environmental pollution Methods 0.000 abstract description 7
- 239000002904 solvent Substances 0.000 abstract description 7
- 239000012535 impurity Substances 0.000 abstract description 6
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 14
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 11
- 239000002994 raw material Substances 0.000 description 8
- 239000007789 gas Substances 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- DYNFCHNNOHNJFG-UHFFFAOYSA-N 2-formylbenzoic acid Chemical compound OC(=O)C1=CC=CC=C1C=O DYNFCHNNOHNJFG-UHFFFAOYSA-N 0.000 description 3
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 3
- 230000007547 defect Effects 0.000 description 3
- 238000007598 dipping method Methods 0.000 description 3
- GHZPDRVHYHFILK-UHFFFAOYSA-N 3-chloro-3h-2-benzofuran-1-one Chemical compound C1=CC=C2C(Cl)OC(=O)C2=C1 GHZPDRVHYHFILK-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 2
- 238000009776 industrial production Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000002791 soaking Methods 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 239000003907 antipyretic analgesic agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- RHDGNLCLDBVESU-UHFFFAOYSA-N but-3-en-4-olide Chemical compound O=C1CC=CO1 RHDGNLCLDBVESU-UHFFFAOYSA-N 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- -1 flunixalate Chemical class 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- JCXJVPUVTGWSNB-UHFFFAOYSA-N nitrogen dioxide Inorganic materials O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
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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
- C07D307/88—Benzo [c] furans; Hydrogenated benzo [c] furans with one oxygen atom directly attached in position 1 or 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
- B01J21/00—Catalysts comprising the elements, oxides, or hydroxides of magnesium, boron, aluminium, carbon, silicon, titanium, zirconium, or hafnium
- B01J21/16—Clays or other mineral silicates
-
- 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
- B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
- B01J23/70—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of the iron group metals or copper
- B01J23/72—Copper
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- 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
- B01J35/50—Catalysts, in general, characterised by their form or physical properties characterised by their shape or configuration
- B01J35/51—Spheres
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- 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
- B01J37/00—Processes, in general, for preparing catalysts; Processes, in general, for activation of catalysts
- B01J37/0009—Use of binding agents; Moulding; Pressing; Powdering; Granulating; Addition of materials ameliorating the mechanical properties of the product catalyst
- B01J37/0027—Powdering
- B01J37/0036—Grinding
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- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J37/00—Processes, in general, for preparing catalysts; Processes, in general, for activation of catalysts
- B01J37/02—Impregnation, coating or precipitation
- B01J37/0201—Impregnation
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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
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- Y02P20/584—Recycling of catalysts
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Abstract
The invention provides a preparation method of 3-bromophthalide, and belongs to the field of 3-bromophthalide. The preparation method of the 3-bromophthalide comprises the following steps: synthesizing and refining. According to the preparation method of the 3-bromophthalide, a specific solvent environment is not required, the process flow is simple, no organic solvent is consumed in the whole production process of the 3-bromophthalide, and the problems of high tail gas treatment difficulty and high environmental pollution caused by volatilization of the organic solvent are effectively avoided; meanwhile, the purity and the reaction yield of the 3-bromophthalide are effectively improved, and the content of impurities (ketone insoluble matters) is reduced.
Description
Technical Field
The invention relates to the field of 3-bromophthalide, in particular to a preparation method of 3-bromophthalide.
Background
3-bromophthalide, also known as 3-bromo-2-benzo [ C ] furanone, has a molecular weight of 213.03, a CAS number of 6940-49-4, and is an off-white or pale yellow crystalline powder having a melting point of 80-86 ℃, a boiling point of 306.9 ℃ (760 mmHg), and a flash point of 139.4 ℃. In the prior art, 3-bromophthalide is a main intermediate for synthesizing compounds such as flunixalate, ampicillin phthalide and the like; meanwhile, the 3-bromophthalide can be further hydrolyzed to prepare o-carboxybenzaldehyde, which is an important intermediate for synthesizing antipyretic analgesic drugs.
At present, the main synthesis method of 3-bromophthalide mainly comprises the following steps:
1) In the environment of chlorobenzene or toluene solvent, using phthalide and bromine as raw materials, and preparing 3-bromophthalide by reaction; specifically, after phthalide is put into chlorobenzene or toluene solvent, bromine is introduced and heated to a proper temperature, and 3-bromophthalide is prepared by heat preservation reaction; wherein, bromine can be added by introducing nitrogen or carbon dioxide to a reaction system after bromine vapor is entrained; or directly dripping bromine into the reaction system. In chinese patent CN101735041B, a method for preparing o-carboxybenzaldehyde is also disclosed, in which chlorobenzene or toluene is used as a solvent, and after phthalide reacts with bromine to prepare 3-bromophthalide, relevant technical information for preparing o-carboxybenzaldehyde by hydrolysis is disclosed. However, the method has the defects that the reaction yield and purity of the prepared 3-bromophthalide are low, the reaction yield can only reach about 80%, the purity is about 98.5wt%, and the impurity (ketone insoluble matter) content is high; meanwhile, the required bromine and chlorobenzene or toluene solvent are large in quantity, the process flow is long, the volatilization of the organic solvent is serious in the production process, the requirement on the matched tail gas treatment process is high, the environmental pollution is high, and the comprehensive production cost is high.
2) In the environment of chlorobenzene or toluene solvent, using phthalide and N-bromosuccinimide (NBS) as raw materials, and preparing the 3-bromophthalide by reaction. However, this method has the disadvantage that the price of N-bromosuccinimide is high, resulting in high production cost; meanwhile, the method has the problems of large amount of chlorobenzene or toluene solvent, long process flow, serious volatilization of the organic solvent in the production process and the like.
3) 3-chlorophthalide is used as raw material to react with phosphorus tribromide to prepare 3-bromophthalide. Although the reaction yield of the 3-bromophthalide prepared by the method can reach 85%, the method has the defects that the raw material 3-chlorophthalide is not easy to purchase, and the phosphorus tribromide has a plurality of problems in the aspects of safety and environmental protection and is not suitable for large-scale industrial production.
Therefore, the defects of the prior art are overcome, and the method has the advantages of low raw material consumption, low solvent demand, simple process flow and low environmental pollution; the prepared 3-bromophthalide has high reaction yield, high purity and low impurity content, and the preparation method of the 3-bromophthalide has important significance.
Disclosure of Invention
In order to solve the technical problems in the prior art, the invention provides a preparation method of 3-bromophthalide, which has the advantages of low raw material consumption, low solvent demand, simple process flow and low environmental pollution; and the prepared 3-bromophthalide has high reaction yield, high purity and low impurity content.
In order to solve the technical problems, the technical scheme adopted by the invention is as follows:
the preparation method of the 3-bromophthalide comprises the following steps: synthesizing and refining.
Mixing phthalide and a catalyst, heating to 140-150 ℃, and preserving heat; dropwise adding bromine under the stirring condition of 40-60 rpm; after the bromine is added dropwise, stirring is continued, and the reaction is carried out for 20-50min under heat preservation; then cooling to 88-92 ℃, adding deionized water, stirring and heating to 60-70 ℃, preserving heat and stirring for 2-3 hours, and filtering out solid matters; then cooling to 10-20 ℃, preserving heat and crystallizing for 3-5 hours, separating out crystals and dehydrating to obtain a crude product of the 3-bromophthalide.
In the synthesis, the dropping rate of bromine is 100-200kg/h;
the molar ratio of phthalide to bromine is 1:1.02-1.05;
the addition amount of the catalyst is 0.5-0.8wt% of the weight of the phthalide;
the weight ratio of deionized water to phthalide is 0.5-0.8:1.
The catalyst is prepared by the following steps: pretreating and soaking.
The preparation method comprises the steps of pretreating, namely adding bentonite, nano silicon dioxide and a silane coupling agent kH-570 into deionized water, heating to 40-50 ℃, preserving heat, stirring for 2-5 hours, filtering, controlling the ball-material ratio to be 5-7:1, controlling the ball-milling rotating speed to be 200-300rpm, controlling the ball-milling time to be 30-60 minutes, granulating to obtain spherical particles with the diameter of 3-5mm after ball milling, and drying for 2-3 hours at 80-90 ℃ to obtain the catalyst carrier.
In the pretreatment, the weight ratio of bentonite to nano silicon dioxide to silane coupling agent kH-570 to deionized water is 4-6:1-2:0.3-0.5:80-100;
the particle size of the bentonite is 65-75 mu m;
the particle size of the nano silicon dioxide is 100-120nm.
And (3) immersing, namely putting the catalyst carrier into an immersion liquid with the volume of 4-8 times, heating to 35-45 ℃, preserving heat, stirring for 5-8 hours, placing in a nitrogen atmosphere environment, heating to 300-400 ℃, preserving heat for 2-3 hours, and naturally cooling to normal temperature to obtain the catalyst.
In the soaking, the heating rate of heating to 300-400 ℃ is 3-5 ℃/min.
The impregnating solution is deionized water solution of boric acid and copper nitrate trihydrate;
boric acid, copper nitrate trihydrate and deionized water in a weight ratio of 5-6:2-3:110-120.
The refining is carried out, the 3-bromophthalide crude product is put into deionized water with the temperature of 70-80 ℃, the temperature is kept, the stirring is carried out at 40-60rpm for 2-3h, and then solid insoluble matters are filtered; cooling to 10-20deg.C, crystallizing for 4-6 hr, separating out crystal, and dehydrating to obtain dehydrated substance; and (3) drying the dehydrated matter to constant weight at 55-65 ℃ under the vacuum degree of 0.03-0.05MPa, thus obtaining the 3-bromophthalide.
In the refining, the weight ratio of deionized water to the 3-bromophthalide crude product is 1.1-1.5:1.
Compared with the prior art, the invention has the beneficial effects that:
(1) According to the preparation method of the 3-bromophthalide, a specific solvent environment is not required, the process flow is simple, no organic solvent is consumed in the whole production process of the 3-bromophthalide, and the problems of high tail gas treatment difficulty and high environmental pollution caused by volatilization of the organic solvent are effectively avoided; meanwhile, by arranging a catalyst carrier with specific composition and impregnating specific composition impregnating solution, the catalyst is prepared, the purity and reaction yield of the 3-bromophthalide are effectively improved, and the content of impurities (ketone insoluble matters) is reduced.
(2) According to the preparation method of the 3-bromophthalide, the purity of the 3-bromophthalide crude product prepared in the synthesis step is 96.7-97.1wt%; the purity of the 3-bromophthalide prepared by the refining step is 99.2-99.6wt%, the content of ketone insoluble matters is 0.02-0.03wt%, and the melting point is 82.1-82.5deg.C.
(3) The preparation method of the 3-bromophthalide of the invention takes raw material phthalide as the basis, and the yield of the prepared 3-bromophthalide is 93.8-94.6%.
(4) Compared with the prior art, the preparation method of the 3-bromophthalide does not need organic solvents such as chlorobenzene or toluene, so that the cost of the organic solvents and the matched devices are effectively saved, and the reagents and the matched devices required for treating the tail gas of the organic solvents are effectively saved; meanwhile, the consumption of raw materials is effectively reduced, and the comprehensive production cost is effectively reduced.
(5) The preparation method of the 3-bromophthalide has the advantages of simple process flow, high production safety and low environmental pollution, and is suitable for large-scale industrial production.
Drawings
FIG. 1 is a gas chromatogram of 3-bromophthalide obtained in example 1.
FIG. 2 is a gas chromatogram of 3-bromophthalide obtained in example 2.
FIG. 3 is a gas chromatogram of 3-bromophthalide obtained in example 3.
Detailed Description
Specific embodiments of the present invention will now be described in order to provide a clearer understanding of the technical features, objects and effects of the present invention.
Example 1
The preparation method of the 3-bromophthalide specifically comprises the following steps:
1. synthesis
Adding phthalide (500 kg,3.73 kmol) and a catalyst (2.5 kg) into a synthesis kettle, heating to 140 ℃, and preserving heat; bromine (608.0 kg,3.80 kmol) is dripped into the synthesis kettle at a dripping speed of 100kg/h under the stirring condition of a stirring rotating speed of 40 rpm; after the bromine is added dropwise, stirring is continued, and the reaction is carried out for 20min at a constant temperature; then cooling to 88 ℃, adding deionized water (250 kg), stirring and heating to 60 ℃, preserving heat and stirring for 2 hours, and filtering out solid matters; then cooling to 10 ℃, preserving heat and crystallizing for 3 hours, separating out crystals and dehydrating to obtain a crude product (770.8 kg) of 3-bromophthalide. The purity of the 3-bromophthalide crude product is 96.7wt%, and the yield is 93.8%.
In the synthesis step of this example, the molar ratio of phthalide to bromine was 1:1.02.
The catalyst was added in an amount of 0.5wt% based on the weight of phthalide.
The weight ratio of deionized water to phthalide is 0.5:1.
The catalyst is prepared by the following method:
1) Pretreatment of
Putting bentonite, nano silicon dioxide and a silane coupling agent kH-570 into deionized water, heating to 40 ℃, preserving heat and stirring for 2 hours, filtering out, transferring into a ball mill, controlling the ball-material ratio to be 5:1, the ball milling rotating speed to be 200rpm, the ball milling time to be 30 minutes, granulating into spherical particles with the diameter of 3mm after ball milling, transferring into a constant temperature drying oven, and drying at 80 ℃ for 2 hours to obtain the catalyst carrier.
Wherein, the weight ratio of bentonite, nano silicon dioxide, silane coupling agent kH-570 and deionized water is 4:1:0.3:80.
The particle size of the bentonite is 65 μm.
The particle size of the nano silicon dioxide is 100nm.
2) Dipping
And (3) putting the catalyst carrier into 4 times volume of impregnating solution, heating to 35 ℃, preserving heat and stirring for 5 hours, filtering out, transferring into a tube furnace, heating to 300 ℃ at a heating rate of 3 ℃/min in a nitrogen atmosphere environment, preserving heat for 2 hours, and naturally cooling to normal temperature to obtain the catalyst.
The preparation method of the impregnating solution comprises the steps of adding boric acid and copper nitrate trihydrate into deionized water, and stirring until the boric acid and the copper nitrate trihydrate are completely dissolved.
Boric acid, copper nitrate trihydrate and deionized water in a weight ratio of 5:2:110.
2. Refining
Deionized water (847.9 kg) is put into a refining kettle, the temperature is raised to 70 ℃, the temperature is kept, under the stirring condition that the stirring rotation speed is 40rpm, 3-bromophthalide crude product (770.8 kg) is put into the refining kettle, and after the stirring is kept for 2 hours, solid insoluble matters are filtered out; then cooling to 10 ℃, preserving heat and crystallizing for 4 hours, separating out crystals and dehydrating to obtain dehydrated matters; the dehydrated matter is dried to constant weight at 55 ℃ under the condition of vacuum degree of 0.03MPa, and 3-bromophthalide (751.4 kg) is prepared. The purity of the 3-bromophthalide is 99.2wt%, the content of ketone insoluble matters is 0.03wt%, and the melting point is 82.1 ℃.
In the refining step of this example, the weight ratio of deionized water to the crude 3-bromophthalide product was 1.1:1.
Example 2
The preparation method of the 3-bromophthalide specifically comprises the following steps:
1. synthesis
Adding phthalide (500 kg,3.73 kmol) and a catalyst (3.25 kg) into a synthesis kettle, heating to 145 ℃, and preserving heat; bromine (613.6, 3.84 kmol) is dripped into the synthesis kettle at a dripping speed of 150kg/h under the stirring condition of 50 rpm; after the bromine is added dropwise, stirring is continued, and the reaction is carried out for 40min at a constant temperature; then cooling to 90 ℃, adding deionized water (325 kg), stirring and heating to 65 ℃, keeping the temperature and stirring for 2.5 hours, and filtering out solid matters; then cooling to 15 ℃, preserving heat and crystallizing for 4 hours, separating out crystals and dehydrating to obtain a crude 3-bromophthalide product (774.1 kg). The purity of the 3-bromophthalide crude product is 97.1wt%, and the yield is 94.6%.
In the synthesis step of this example, the molar ratio of phthalide to bromine was 1:1.03.
The catalyst was added in an amount of 0.65wt% based on the weight of phthalide.
The weight ratio of deionized water to phthalide is 0.65:1.
The catalyst is prepared by the following method:
1) Pretreatment of
Putting bentonite, nano silicon dioxide and a silane coupling agent kH-570 into deionized water, heating to 45 ℃, preserving heat and stirring for 3 hours, filtering out, transferring into a ball mill, controlling the ball-material ratio to be 6:1, the ball milling rotating speed to be 250rpm, the ball milling time to be 40 minutes, granulating into spherical particles with the diameter of 4mm after ball milling, transferring into a constant temperature drying oven, and drying at 85 ℃ for 2.5 hours to obtain the catalyst carrier.
Wherein, the weight ratio of bentonite, nano silicon dioxide, silane coupling agent kH-570 and deionized water is 5:1.5:0.4:90.
The particle size of the bentonite is 70 μm.
The particle size of the nano silicon dioxide is 110nm.
2) Dipping
And (3) putting the catalyst carrier into a 6-time volume of impregnating solution, heating to 40 ℃, preserving heat and stirring for 6.5 hours, filtering out, transferring into a tube furnace, heating to 350 ℃ at a heating rate of 4 ℃/min in a nitrogen atmosphere environment, preserving heat for 2.5 hours, and naturally cooling to normal temperature to obtain the catalyst.
The preparation method of the impregnating solution comprises the steps of adding boric acid and copper nitrate trihydrate into deionized water, and stirring until the boric acid and the copper nitrate trihydrate are completely dissolved.
Boric acid, copper nitrate trihydrate and deionized water in a weight ratio of 5.5:2.5:115.
2. Refining
Deionized water (1006.3 kg) is put into a refining kettle, the temperature is raised to 75 ℃, the temperature is kept, under the stirring condition that the stirring speed is 50rpm, 3-bromophthalide crude product (774.1 kg) is put into the refining kettle, the temperature is kept, the stirring is carried out for 2.5h, and then solid insoluble matters are filtered out; then cooling to 15 ℃, preserving heat and crystallizing for 5 hours, separating out crystals and dehydrating to obtain dehydrated matters; the dehydrated matter is dried to constant weight at 60 ℃ under the condition of vacuum degree of 0.04MPa, and 3-bromophthalide (754.7 kg) is prepared. The purity of the 3-bromophthalide is 99.6wt%, the content of ketone insoluble matters is 0.02wt%, and the melting point is 82.5 ℃.
In the refining step of this example, the weight ratio of deionized water to the crude 3-bromophthalide product was 1.3:1.
Example 3
The preparation method of the 3-bromophthalide specifically comprises the following steps:
1. synthesis
Adding phthalide (500 kg,3.73 kmol) and a catalyst (4.0 kg) into a synthesis kettle, heating to 150 ℃, and preserving heat; bromine (625.9 kg,3.92 kmol) was dropped into the synthesis vessel at a dropping rate of 200kg/h under stirring at a stirring speed of 60 rpm; after the bromine is added dropwise, stirring is continued, and the reaction is carried out for 50min at a constant temperature; then cooling to 92 ℃, adding deionized water (400 kg), stirring and heating to 70 ℃, preserving heat and stirring for 3 hours, and filtering out solid matters; then cooling to 20 ℃, preserving heat and crystallizing for 5 hours, separating out crystals and dehydrating to obtain a crude 3-bromophthalide product (772.5 kg). The purity of the 3-bromophthalide crude product is 96.9wt%, and the yield is 94.2%.
In the synthesis procedure of this example, the molar ratio of phthalide to bromine was 1:1.05.
The catalyst was added in an amount of 0.8wt% based on the weight of phthalide.
The weight ratio of deionized water to phthalide is 0.8:1.
The catalyst is prepared by the following method:
1) Pretreatment of
Putting bentonite, nano silicon dioxide and a silane coupling agent kH-570 into deionized water, heating to 50 ℃, preserving heat and stirring for 5 hours, filtering out, transferring into a ball mill, controlling the ball-material ratio to be 7:1, the ball milling rotating speed to be 300rpm, the ball milling time to be 60 minutes, granulating into spherical particles with the diameter of 5mm after ball milling, transferring into a constant temperature drying oven, and drying at 90 ℃ for 3 hours to obtain the catalyst carrier.
Wherein, the weight ratio of bentonite, nano silicon dioxide, silane coupling agent kH-570 and deionized water is 6:2:0.5:100.
The particle size of the bentonite is 75 μm.
The particle size of the nano silicon dioxide is 120nm.
2) Dipping
And (3) putting the catalyst carrier into 8 times volume of impregnating solution, heating to 45 ℃, preserving heat and stirring for 8 hours, filtering out, transferring into a tube furnace, heating to 400 ℃ at a heating rate of 5 ℃/min in a nitrogen atmosphere environment, preserving heat for 3 hours, and naturally cooling to normal temperature to obtain the catalyst.
The preparation method of the impregnating solution comprises the steps of adding boric acid and copper nitrate trihydrate into deionized water, and stirring until the boric acid and the copper nitrate trihydrate are completely dissolved.
Boric acid, copper nitrate trihydrate and deionized water in a weight ratio of 6:3:120.
2. Refining
Deionized water (1158.8 kg) is put into a refining kettle, the temperature is raised to 80 ℃, the temperature is kept, under the stirring condition that the stirring speed is 60rpm, 3-bromophthalide crude product (772.5 kg) is put into the refining kettle, the temperature is kept, the stirring is carried out for 3 hours, and then solid insoluble matters are filtered; then cooling to 20 ℃, preserving heat and crystallizing for 6 hours, separating out crystals and dehydrating to obtain dehydrated matters; the dehydrated matter is dried to constant weight at 65 ℃ under the condition of vacuum degree of 0.05MPa, and 3-bromophthalide (753.1 kg) is prepared. The purity of the 3-bromophthalide is 99.4wt%, the content of ketone insoluble matters is 0.02wt%, and the melting point is 82.3 ℃.
In the refining step of this example, the weight ratio of deionized water to the crude 3-bromophthalide product was 1.5:1.
Comparative example 1
The technical scheme of the embodiment 2 is adopted, and the difference is that: in the synthesis step, the addition of the catalyst is omitted.
In comparative example 1, the purity of the crude 3-bromophthalide product obtained in the synthesis step was 95.7% by weight, and the yield was 90.0%. The purity of the 3-bromophthalide obtained in the refining step was 98.0% by weight, and the content of ketone insoluble matter was 0.12% by weight.
Comparative example 2
The technical scheme of the embodiment 2 is adopted, and the difference is that: 1) Omitting the pretreatment step of catalyst preparation, modifying to granulate bentonite with the particle size of 70 μm into spherical particles with the diameter of 4mm, and drying to prepare a catalyst carrier; 2) Boric acid is omitted from the impregnating solution in the impregnating step.
In comparative example 2, the purity of the crude 3-bromophthalide product obtained in the synthesis step was 96.1% by weight, and the yield was 91.7%. The purity of the 3-bromophthalide obtained in the refining step was 98.5% by weight, and the content of ketone insoluble matter was 0.1% by weight.
It can be seen that the preparation method of 3-bromophthalide in embodiments 1-3 of the invention does not need to set a specific solvent environment, has simple process flow, has no solvent consumption in the whole production process of 3-bromophthalide, and effectively avoids the problems of high tail gas treatment difficulty and high environmental pollution caused by volatilization of an organic solvent; meanwhile, by arranging a catalyst carrier with specific composition and impregnating specific composition impregnating solution, the catalyst is prepared, the purity and reaction yield of the 3-bromophthalide are effectively improved, and the content of impurities (ketone insoluble matters) is reduced.
The percentages used in the present invention are mass percentages unless otherwise indicated.
Finally, it should be noted that: the foregoing description is only a preferred embodiment of the present invention, and the present invention is not limited thereto, but it is to be understood that modifications and equivalents of some of the technical features described in the foregoing embodiments may be made by those skilled in the art, although the present invention has been described in detail with reference to the foregoing embodiments. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (6)
1. A method for preparing 3-bromophthalide, which is characterized by comprising the following steps: synthesizing and refining;
mixing phthalide and a catalyst, heating to 140-150 ℃, and preserving heat; dropwise adding bromine under stirring; after the bromine is added dropwise, stirring is continued, and the reaction is carried out for 20-50min under heat preservation; then cooling to 88-92 ℃, adding deionized water, stirring and heating to 60-70 ℃, preserving heat and stirring for 2-3 hours, and filtering out solid matters; then cooling to 10-20 ℃, preserving heat and crystallizing for 3-5 hours, separating out crystals and dehydrating to obtain a 3-bromophthalide crude product;
the catalyst is prepared by the following steps: pretreatment and impregnation;
the preparation method comprises the steps of preprocessing, namely adding bentonite, nano silicon dioxide and a silane coupling agent kH-570 into deionized water, heating to 40-50 ℃, preserving heat and stirring for a certain time, filtering, ball-milling for a certain time, granulating into spherical particles with the diameter of 3-5mm, and drying for 2-3 hours at 80-90 ℃ to prepare a catalyst carrier;
the impregnation is carried out, the catalyst carrier is put into impregnating solution with the volume of 4-8 times, the temperature is raised to 35-45 ℃, after the catalyst carrier is stirred for a certain time in a nitrogen atmosphere, the catalyst carrier is heated to 300-400 ℃, the temperature is kept for 2-3 hours, and the catalyst is naturally cooled to normal temperature, so that the catalyst is prepared;
the impregnating solution is deionized water solution of boric acid and copper nitrate trihydrate;
the refining is carried out, the 3-bromophthalide crude product is put into deionized water with the temperature of 70-80 ℃, and after the mixture is stirred for a certain time in a heat preservation way, solid insoluble matters are filtered out; cooling to 10-20deg.C, crystallizing for 4-6 hr, separating out crystal, and dehydrating to obtain dehydrated substance; and (3) drying the dehydrated matter to constant weight at 55-65 ℃ under the vacuum degree of 0.03-0.05MPa, thus obtaining the 3-bromophthalide.
2. The method for preparing 3-bromophthalide according to claim 1, characterized in that in the synthesis, the dropping rate of bromine is 100-200kg/h;
the molar ratio of phthalide to bromine is 1:1.02-1.05.
3. The method for preparing 3-bromophthalide according to claim 1, wherein the catalyst is added in an amount of 0.5-0.8wt% based on the weight of phthalide in the synthesis;
the weight ratio of deionized water to phthalide is 0.5-0.8:1.
4. The preparation method of 3-bromophthalide according to claim 1, wherein in the pretreatment, the weight ratio of bentonite, nano silicon dioxide, a silane coupling agent kH-570 and deionized water is 4-6:1-2:0.3-0.5:80-100;
the particle size of the bentonite is 65-75 mu m;
the particle size of the nano silicon dioxide is 100-120nm.
5. The method for producing 3-bromophthalide according to claim 1, characterized in that, in the impregnation, a heating rate to 300-400 ℃ is 3-5 ℃/min;
boric acid, copper nitrate trihydrate and deionized water in a weight ratio of 5-6:2-3:110-120.
6. The method for preparing 3-bromophthalide according to claim 1, wherein the weight ratio of deionized water to 3-bromophthalide crude product in the refining is 1.1-1.5:1.
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1537815A (en) * | 1976-11-17 | 1979-01-04 | Dynamit Nobel Ag | Process for producing 3-bromophthalide |
| GB2009175A (en) * | 1977-12-01 | 1979-06-13 | Dynamit Nobel Ag | Process for Producing 3- Bromophthalide |
| US4211710A (en) * | 1977-05-11 | 1980-07-08 | Dynamit Nobel Aktiengesellschaft | Process of preparing 3-bromophthalide |
| CN101735041A (en) * | 2009-12-17 | 2010-06-16 | 太仓市运通化工厂 | Preparation method of 2-carboxybenzaldehyde |
| CN104447303A (en) * | 2014-11-26 | 2015-03-25 | 太仓运通生物化工有限公司 | Preparation technology of carboxybenzaldehyde |
| CN105665015A (en) * | 2016-01-13 | 2016-06-15 | 济南大学 | Solid acid catalyst, preparation method and application thereof |
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Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1537815A (en) * | 1976-11-17 | 1979-01-04 | Dynamit Nobel Ag | Process for producing 3-bromophthalide |
| US4211710A (en) * | 1977-05-11 | 1980-07-08 | Dynamit Nobel Aktiengesellschaft | Process of preparing 3-bromophthalide |
| GB2009175A (en) * | 1977-12-01 | 1979-06-13 | Dynamit Nobel Ag | Process for Producing 3- Bromophthalide |
| CN101735041A (en) * | 2009-12-17 | 2010-06-16 | 太仓市运通化工厂 | Preparation method of 2-carboxybenzaldehyde |
| CN104447303A (en) * | 2014-11-26 | 2015-03-25 | 太仓运通生物化工有限公司 | Preparation technology of carboxybenzaldehyde |
| CN105665015A (en) * | 2016-01-13 | 2016-06-15 | 济南大学 | Solid acid catalyst, preparation method and application thereof |
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