CN116554098A - Method for rapidly synthesizing 2-hydroxy acridone under assistance of ultrasonic waves by one-pot method - Google Patents
Method for rapidly synthesizing 2-hydroxy acridone under assistance of ultrasonic waves by one-pot method Download PDFInfo
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- IQJICBDZRSNSEJ-UHFFFAOYSA-N 2-hydroxy-10h-acridin-9-one Chemical compound C1=CC=C2C(=O)C3=CC(O)=CC=C3NC2=C1 IQJICBDZRSNSEJ-UHFFFAOYSA-N 0.000 title claims abstract description 110
- 238000000034 method Methods 0.000 title claims abstract description 41
- 238000005580 one pot reaction Methods 0.000 title claims abstract description 17
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 14
- 238000006243 chemical reaction Methods 0.000 claims abstract description 40
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 28
- BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical compound COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 claims abstract description 27
- XRXMNWGCKISMOH-UHFFFAOYSA-N 2-bromobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1Br XRXMNWGCKISMOH-UHFFFAOYSA-N 0.000 claims abstract description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 18
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims abstract description 13
- 238000001816 cooling Methods 0.000 claims abstract description 13
- 238000004821 distillation Methods 0.000 claims abstract description 13
- 230000035484 reaction time Effects 0.000 claims abstract description 8
- 239000000463 material Substances 0.000 claims description 17
- 239000002904 solvent Substances 0.000 claims description 16
- 239000007788 liquid Substances 0.000 claims description 15
- 238000003756 stirring Methods 0.000 claims description 12
- 239000010410 layer Substances 0.000 claims description 11
- 238000000967 suction filtration Methods 0.000 claims description 6
- 230000015572 biosynthetic process Effects 0.000 claims description 5
- 239000012044 organic layer Substances 0.000 claims description 5
- 238000003786 synthesis reaction Methods 0.000 claims description 5
- 239000002994 raw material Substances 0.000 abstract description 11
- 239000003054 catalyst Substances 0.000 abstract description 3
- 238000005265 energy consumption Methods 0.000 abstract description 2
- 239000011541 reaction mixture Substances 0.000 abstract 1
- 238000001953 recrystallisation Methods 0.000 abstract 1
- 239000000047 product Substances 0.000 description 15
- FZEYVTFCMJSGMP-UHFFFAOYSA-N acridone Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3NC2=C1 FZEYVTFCMJSGMP-UHFFFAOYSA-N 0.000 description 12
- 238000005303 weighing Methods 0.000 description 9
- GDALETGZDYOOGB-UHFFFAOYSA-N Acridone Natural products C1=C(O)C=C2N(C)C3=CC=CC=C3C(=O)C2=C1O GDALETGZDYOOGB-UHFFFAOYSA-N 0.000 description 8
- 239000003814 drug Substances 0.000 description 6
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 229940079593 drug Drugs 0.000 description 5
- SMPZPKRDRQOOHT-UHFFFAOYSA-N acronycine Chemical compound CN1C2=CC=CC=C2C(=O)C2=C1C(C=CC(C)(C)O1)=C1C=C2OC SMPZPKRDRQOOHT-UHFFFAOYSA-N 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- DMBHHRLKUKUOEG-UHFFFAOYSA-N diphenylamine Chemical compound C=1C=CC=CC=1NC1=CC=CC=C1 DMBHHRLKUKUOEG-UHFFFAOYSA-N 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 238000001308 synthesis method Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 238000002441 X-ray diffraction Methods 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- -1 clinical diagnosis Substances 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000000049 pigment Substances 0.000 description 3
- 230000001376 precipitating effect Effects 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000005855 radiation Effects 0.000 description 3
- IKCLCGXPQILATA-UHFFFAOYSA-N 2-chlorobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1Cl IKCLCGXPQILATA-UHFFFAOYSA-N 0.000 description 2
- IYLLULUTZPKQBW-UHFFFAOYSA-N Acrinol Chemical compound CC(O)C(O)=O.C1=C(N)C=CC2=C(N)C3=CC(OCC)=CC=C3N=C21 IYLLULUTZPKQBW-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 238000003759 clinical diagnosis Methods 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- 150000002894 organic compounds Chemical class 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- BPXINCHFOLVVSG-UHFFFAOYSA-N 9-chloroacridine Chemical compound C1=CC=C2C(Cl)=C(C=CC=C3)C3=NC2=C1 BPXINCHFOLVVSG-UHFFFAOYSA-N 0.000 description 1
- 206010000830 Acute leukaemia Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- NRCMAYZCPIVABH-UHFFFAOYSA-N Quinacridone Chemical compound N1C2=CC=CC=C2C(=O)C2=C1C=C1C(=O)C3=CC=CC=C3NC1=C2 NRCMAYZCPIVABH-UHFFFAOYSA-N 0.000 description 1
- 238000006887 Ullmann reaction Methods 0.000 description 1
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- XCPGHVQEEXUHNC-UHFFFAOYSA-N amsacrine Chemical compound COC1=CC(NS(C)(=O)=O)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 XCPGHVQEEXUHNC-UHFFFAOYSA-N 0.000 description 1
- 229960001220 amsacrine Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000002141 anti-parasite Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000003096 antiparasitic agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- ZWJINEZUASEZBH-UHFFFAOYSA-N fenamic acid Chemical compound OC(=O)C1=CC=CC=C1NC1=CC=CC=C1 ZWJINEZUASEZBH-UHFFFAOYSA-N 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000006115 industrial coating Substances 0.000 description 1
- 201000004792 malaria Diseases 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000015654 memory Effects 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- KVNYFPKFSJIPBJ-UHFFFAOYSA-N ortho-diethylbenzene Natural products CCC1=CC=CC=C1CC KVNYFPKFSJIPBJ-UHFFFAOYSA-N 0.000 description 1
- 230000010355 oscillation Effects 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- YLLIGHVCTUPGEH-UHFFFAOYSA-M potassium;ethanol;hydroxide Chemical compound [OH-].[K+].CCO YLLIGHVCTUPGEH-UHFFFAOYSA-M 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000004467 single crystal X-ray diffraction Methods 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 238000003809 water extraction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D219/00—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems
- C07D219/04—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the ring system
- C07D219/06—Oxygen atoms
-
- 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
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a method for quickly synthesizing 2-hydroxy acridone by using one-pot ultrasonic assistance, which comprises the steps of dissolving 2-bromobenzoic acid in DMF to form solution A, dissolving p-methoxyaniline in DMF to form solution B, adding copper powder as a catalyst into a reaction vessel, adding the solution A and the solution B into the reaction vessel, placing the obtained reaction mixture into an ultrasonic reactor, performing ultrasonic assistance reaction for 45-60min, cooling, performing reduced pressure distillation, adding hot water to extract a product, and purifying the obtained crude 2-hydroxy acridone by ethanol recrystallization to obtain high-purity 2-hydroxy acridone. The invention prepares the target product 2-hydroxy acridone by adopting an ultrasonic-assisted one-pot method at the reaction temperature of about 50 ℃, has simple process steps, convenient operation, short reaction time, mild reaction conditions, easily obtained raw materials and high yield, greatly reduces the loss of the raw materials, shortens the reaction time and reduces the reaction energy consumption.
Description
Technical Field
The invention relates to the technical field of preparation and purification of organic compounds, in particular to a method for rapidly synthesizing 2-hydroxy acridone by using one-pot ultrasonic assistance.
Background
Acridone is an organic compound based on an acridine skeleton, and has a carbonyl group at the 9-position. Most acridone compounds are yellow flaky crystals which are soluble in hot ethanol, hot acetic acid, potassium hydroxide ethanol solution, insoluble in water, diethyl ether, benzene and chloroform, and exhibit blue fluorescence in ethanol solution.
The acridone derivative is widely applied to a plurality of fields such as medicines, clinical diagnosis, chemical dyes and the like. The method mainly comprises the following steps:
in the field of medicines, a plurality of medicines synthesized by acridine and acridone compounds are widely applied to clinical researches, such as Acronycine (Acronycine) has a strong broad-spectrum anti-tumor effect and is clinically used as an anti-cancer medicine; aleppine (ataberine) has been widely used in the last century to prevent and treat malaria; amsacrine (amacrime) is used clinically to treat acute leukemia; rivanol (rivanol) was used as a midterm pregnancy induction drug. In addition, acridone derivatives are also widely studied in a number of fields of antiviral, antiparasitic, antiinflammatory, memory improving, etc.
In the clinical diagnosis field, the acridone derivative as an enhanced fluorescent signal probe has the characteristics of small sampling amount, high sensitivity, lower detection limit, rapid response, high stability, convenient operation and the like. There has been an increase in recent years in reports concerning the correlation thereof.
In the field of dyes, quinacridone pigments have the characteristics of vivid and transparent color, stability, remarkable heat resistance, solvent resistance, light resistance and the like, are widely applied to automobiles, industrial coatings, plastics, printing ink, cosmetics and the like, and are a pigment which is not separated from our daily lives.
2-hydroxy acridone is an intermediate in the synthesis of many drugs and pigments. At present, few reports are about the synthesis method of hydroxy acridone, and most of the synthesis methods adopt a Ullmann reaction catalyzed by Cu. The main reaction process comprises the steps of firstly preparing o- (N-phenylamino) benzoic acid by using o-chlorobenzoic acid and aniline under the action of copper powder, potassium carbonate and nitrobenzene, and then reacting for 2 hours at 100 ℃ under the catalysis of phosphorus oxychloride to obtain acridone. The synthesis method can synthesize the target product by two steps of reactions, has complex reactions, more byproducts and complex operation steps, and is more severe to the dosage of phosphorus oxychloride, because the acridone is very easy to be converted into 9-chloroacridine under the action of the phosphorus oxychloride. Thus, this method has many disadvantages both in terms of operation and in terms of yield. In addition, there are reports of the use of diphenylamine and carboxylic acid compounds in ZnCl 2 The method has the advantages that the operation steps are simpler, the reaction time is particularly long, the byproducts are more, the experimental conditions are extremely strict, meanwhile, the diphenylamine has high risk, and the inhalation, the swallowing, the skin contact and the like can cause harm to human bodies.
Therefore, the synthesis method of the acridone and the derivative thereof is researched and designed, so that the preparation of the acridone and the derivative thereof can be completed rapidly, conveniently, efficiently, environmentally-friendly and at low cost, and the method is necessary for reducing the production cost of the acridone and the derivative thereof and expanding the application range thereof.
Disclosure of Invention
The invention aims to provide a method for quickly synthesizing 2-hydroxy acridone by using one-pot ultrasonic wave as an auxiliary, which uses copper powder as a catalyst to quickly, efficiently and high-yield prepare a target product 2-hydroxy acridone by using the ultrasonic wave as an auxiliary under the condition of 50 ℃, and has the advantages of simple process steps, convenient operation, short reaction time, mild reaction condition, easily obtained raw materials, high yield, greatly reduced loss of the raw materials, shortened reaction time, reduced reaction energy consumption, waste avoidance and reduced process cost.
The invention is realized by the following technical scheme, and the method for rapidly synthesizing 2-hydroxy acridone by one-pot ultrasonic assistance provided by the invention comprises the following steps:
(1) Placing a certain amount of 2-bromobenzoic acid into a beaker, adding DMF solvent, and magnetically stirring to dissolve the 2-bromobenzoic acid to obtain solution A for later use;
(2) Placing a certain amount of p-methoxyaniline into a new beaker, adding DMF solvent into the beaker, and magnetically stirring to dissolve the p-methoxyaniline to obtain solution B for later use;
(3) Putting a certain amount of copper powder into a round-bottom flask, slowly pouring the solution A in the step (1) and the solution B in the step (2) into the round-bottom flask to obtain a mixed material for later use; wherein the mass of the copper powder is 2-5% of the mass of the 2-bromobenzoic acid;
(4) Placing the round-bottom flask filled with the mixed material in the step (3) in an ultrasonic reactor, adopting ultrasonic-assisted reaction, and naturally cooling to room temperature after the reaction is finished;
(5) Distilling the cooled material in the step (4) under reduced pressure and recovering excessive p-methoxyaniline;
(6) Transferring the residual liquid after the reduced pressure distillation in the step (5) into a separating funnel, adding hot water into the separating funnel, sufficiently oscillating to enable 2-hydroxy acridone to be sufficiently transferred into the hot water, standing the separating funnel, separating liquid after the liquid is layered, discarding an organic layer, taking a water layer, standing the obtained water layer, naturally cooling, and carrying out suction filtration to obtain filter residues, namely crude 2-hydroxy acridone;
(7) Recrystallizing the crude 2-hydroxy acridone with ethanol to obtain high-purity 2-hydroxy acridone, wherein the structural formula is as follows:
the method for rapidly synthesizing the 2-hydroxy acridone by the ultrasonic assistance of the one-pot method is characterized in that the molar ratio of the p-methoxyaniline to the 2-bromobenzoic acid is (1-1.2): 1, and the purities of the 2-bromobenzoic acid and the p-methoxyaniline are not less than 99 percent.
Preferably, the volume ratio of the mass of 2-bromobenzoic acid to DMF in step (1) is 1g (10-15) ml.
Preferably, the volume ratio of the mass of the p-methoxyaniline to the DMF in the step (2) is 1g (20-25) ml.
Preferably, the conditions for the ultrasound-assisted reaction in step (4) are set as follows: the ultrasonic frequency is 60-65KHz, the power is 400W, the reaction temperature is 50 ℃, and the reaction time is 45-60min.
Preferably, the temperature of the hot water added in the separating funnel in the step (5) is 50+/-5 ℃, and the adding volume of the hot water is 2-3 times of the volume of the DMF in the step (1).
The method for rapidly synthesizing the 2-hydroxy acridone by the ultrasonic assistance of the one-pot method can finally prepare the high-purity 2-hydroxy acridone with the molar yield of more than 85 percent.
Compared with the prior art, the invention has obvious advantages and beneficial effects. By means of the technical scheme, the invention can achieve quite technical progress and practicability, has wide utilization value, and has at least the following advantages:
(1) Compared with the traditional two-step process for synthesizing 2-hydroxy acridone, the method disclosed by the invention has the advantages that 2-bromobenzoic acid and p-methoxy aniline are used as raw materials, copper powder is used as a catalyst, under the action of ultrasonic waves, the copper powder is contacted with reactants more uniformly, the contact area is larger, the catalytic effect is enhanced, the activation energy of the reaction is reduced, the reaction can be efficiently carried out at a lower temperature, and the target product is synthesized in one step. More importantly, the process raw material of the invention replaces the 2-chlorobenzoic acid which is conventionally used with the 2-bromobenzoic acid, the bond force of the carbon bond connected with bromine in the 2-bromobenzoic acid is weaker and is easier to hydrolyze, the loss of the raw material is greatly reduced, the yield is improved, and the waste is avoided.
(2) The invention adopts the mode of ultrasonic radiation auxiliary reaction in the synthesis process, and makes the intermolecular contact of the raw materials more uniform and sufficient, the contact area between the raw materials is larger, the reaction and bonding are quicker, more sufficient and thorough, and the conversion rate of the target product is higher through ultrasonic oscillation at a lower temperature (50 ℃) under specific ultrasonic frequency and power. The experiment shows that the reaction rate of the process is about 5 times faster than that of the traditional method, the molar yield of the target compound 2-hydroxy acridone can reach more than 85%, the reaction time is greatly shortened, and the reaction efficiency, the purity of the finished product compound and the yield are improved.
Drawings
FIG. 1 is a single crystal XRD pattern of the finished compound prepared in example 1 of the present invention;
FIG. 2 is a graph showing diffraction peaks of the final compound prepared in example 1 of the present invention.
Detailed Description
For the purpose of making the objects, technical solutions and advantages of the embodiments of the present invention more apparent, the technical solutions of the present invention will be clearly and completely described below in conjunction with specific embodiments, and it is apparent that the described embodiments are some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to fall within the scope of the invention.
The method for rapidly synthesizing the acridone and the derivative-2-hydroxy acridone by the one-pot method with the assistance of ultrasonic waves takes 2-bromobenzoic acid and p-methoxy aniline as raw materials, the purity of the 2-bromobenzoic acid and the p-methoxy aniline is not less than 99%, the rapid and efficient preparation of the 2-hydroxy acridone is realized by the assistance of the ultrasonic wave radiation of the ultrasonic waves, and the technological method is mainly characterized in that the material proportion among the reaction raw materials, the setting of ultrasonic wave radiation frequency parameters, the separation and purification modes of reaction products and the like. The specific process steps comprise:
(1) Placing a certain amount of 2-bromobenzoic acid into a beaker, adding DMF solvent, and magnetically stirring to completely dissolve the 2-bromobenzoic acid to obtain solution A for later use;
(2) Placing a certain amount of p-methoxyaniline into a new beaker, adding DMF solvent into the beaker, and magnetically stirring to completely dissolve the p-methoxyaniline to obtain solution B for later use;
(3) Putting a certain amount of copper powder into a round-bottom flask, slowly pouring the solution A in the step (1) and the solution B in the step (2) into the round-bottom flask to obtain a mixed material for later use;
(4) Placing the round-bottom flask filled with the mixed material in the step (3) in an ultrasonic reactor, setting the ultrasonic frequency to be 60-65KHz, the power to be 400W, heating the round-bottom flask to be 50 ℃, performing ultrasonic auxiliary reaction for 45-60min, and naturally cooling the round-bottom flask to room temperature after the reaction is finished;
the reaction equation of this step is:
(5) Distilling the cooled material in the step (4) under reduced pressure and recovering excessive p-methoxyaniline;
(6) Adding hot water into the residual liquid after the reduced pressure distillation in the step (5), extracting a product by adopting a hot water extraction mode, standing a water layer obtained after extraction, naturally cooling and carrying out suction filtration, wherein the obtained filter residue is crude 2-hydroxy acridone;
(7) And recrystallizing the crude 2-hydroxy acridone with ethanol to obtain high-purity 2-hydroxy acridone.
The structural formula of the obtained target product 2-hydroxy acridone is as follows:
the present invention is described in detail below with reference to specific examples, and the experimental methods and detection methods described in the following examples are conventional methods in the art unless otherwise specified; the experimental process is carried out under normal temperature and normal pressure unless indicated; the reagents and materials are commercially available unless otherwise specified. The calculation formula of the yield (molar yield) of the high-purity 2-hydroxy acridone of the product in the examples is as follows:
example 1
(1) Accurately weighing 2.01g (0.01 mol) of 2-bromobenzoic acid, placing in a beaker, adding 20ml of DMF solvent, and magnetically stirring to completely dissolve the 2-bromobenzoic acid to obtain a solution A for later use;
(2) Accurately weighing 1.48g (0.012 mol) of p-methoxyaniline, placing in a new beaker, adding 30ml of DMF solvent into the beaker, and magnetically stirring to completely dissolve the p-methoxyaniline to obtain a solution B for later use;
(3) Putting 0.06g of copper powder into a round-bottom flask, slowly pouring the solution A in the step (1) and the solution B in the step (2) into the round-bottom flask to obtain a mixed material for later use;
(4) Placing the round-bottom flask filled with the mixed material in the step (3) in an ultrasonic reactor, setting the ultrasonic frequency to be 60KHz, the power to be 400W, heating the round-bottom flask to the temperature of 50 ℃, performing ultrasonic auxiliary reaction, stopping the reaction after 60min, and naturally cooling the product to the room temperature;
(5) Transferring the product solution cooled in the step (4) into a distillation device, and performing reduced pressure distillation to distill off the p-methoxyaniline;
(6) Transferring the residual liquid after the reduced pressure distillation in the step (5) to a separating funnel, adding 50ml of hot water with the temperature of about 50 ℃ (50+/-5 ℃) into the separating funnel, immediately and fully vibrating, fully transferring the 2-hydroxy acridone into the added hot water solvent, and then standing the separating funnel. After layering, separating liquid, taking a water layer, discarding an organic layer, standing the water layer, standing for cooling, and carrying out suction filtration to obtain filter residues, namely crude 2-hydroxy acridone;
(7) Recrystallizing the crude 2-hydroxy acridone with ethanol, precipitating, suction filtering to obtain high purity 2-hydroxy acridone, drying, weighing to obtain high purity 2-hydroxy acridone with mass of 1.84g, and calculating the yield of 87.2% according to the above yield formula.
The prepared high-purity 2-hydroxy acridone was subjected to elemental analysis using a Perkin-Elmer 1400C type elemental analyzer. The data obtained are: c:73.87% (73.93% of theory), H:4.39% (theoretical 4.26%), N:6.76% (theoretical 6.64%) O:14.98% (15.17% of theory). The analytical values of the products are substantially identical to the theoretical values.
The high-purity 2-hydroxy acridone prepared in the embodiment is subjected to single crystal X-ray diffraction analysis and detection, and a single crystal XRD pattern is obtained by analyzing by using Mercury software, and the single crystal XRD pattern and a diffraction peak pattern are respectively shown in fig. 1 and 2.
Example 2
(1) Accurately weighing 4.02g (0.02 mol) of 2-bromobenzoic acid, placing in a beaker, adding 50ml of DMF solvent, and magnetically stirring to completely dissolve the 2-bromobenzoic acid to obtain a solution A for later use;
(2) Accurately weighing 2.71g (0.022 mol) of p-methoxyaniline, placing in a new beaker, adding 60ml of DMF solvent into the beaker, and magnetically stirring to completely dissolve the p-methoxyaniline to obtain a solution B for later use;
(3) Putting 0.12g of copper powder into a round-bottom flask, slowly pouring the solution A in the step (1) and the solution B in the step (2) into the round-bottom flask to obtain a mixed material for later use;
(4) Placing the round-bottom flask filled with the mixed material in the step (3) in an ultrasonic reactor, setting the ultrasonic frequency to be 65KHz, the power to be 400W, heating the round-bottom flask to the temperature of 50 ℃, performing ultrasonic auxiliary reaction, stopping the reaction after 45min, and naturally cooling the product to the room temperature;
(5) Transferring the product solution cooled in the step (4) into a distillation device, and performing reduced pressure distillation to distill off the p-methoxyaniline;
(6) Transferring the residual liquid after the reduced pressure distillation in the step (5) to a separating funnel, adding 100ml of hot water with the temperature of about 50 ℃ (50+/-5 ℃) into the separating funnel, immediately and fully vibrating, fully transferring the 2-hydroxy acridone into the added hot water solvent, and then standing the separating funnel. Separating liquid after the liquid is layered, taking a water layer, discarding an organic layer, standing the water layer, standing for cooling, and carrying out suction filtration to obtain filter residues, namely crude 2-hydroxy acridone;
(7) Recrystallizing the crude 2-hydroxy acridone with ethanol, precipitating, suction filtering to obtain high purity 2-hydroxy acridone, drying, weighing to obtain high purity 2-hydroxy acridone with mass of 3.78g, and calculating the yield of 89.6% according to the above yield formula.
Example 3
(1) Accurately weighing 4.02g (0.02 mol) of 2-bromobenzoic acid, placing in a beaker, adding 50ml of DMF solvent, and magnetically stirring to completely dissolve the 2-bromobenzoic acid to obtain a solution A for later use;
(2) Accurately weighing 2.46g (0.02 mol) of p-methoxyaniline, placing in a new beaker, adding 60ml of DMF solvent into the beaker, and magnetically stirring to completely dissolve the p-methoxyaniline to obtain a solution B for later use;
(3) Putting 0.12g of copper powder into a round-bottom flask, slowly pouring the solution A in the step (1) and the solution B in the step (2) into the round-bottom flask to obtain a mixed material for later use;
(4) Placing the round-bottom flask filled with the mixed material in the step (3) in an ultrasonic reactor, setting the ultrasonic frequency to be 60KHz, the power to be 400W, heating the round-bottom flask to the temperature of 50 ℃, performing ultrasonic auxiliary reaction, stopping the reaction after 50min, and naturally cooling the product to the room temperature;
(5) Transferring the product solution cooled in the step (4) into a distillation device, and performing reduced pressure distillation to distill off the p-methoxyaniline;
(6) Transferring the residual liquid after the reduced pressure distillation in the step (5) to a separating funnel, adding 100ml of hot water with the temperature of about 50 ℃ (50+/-5 ℃) into the separating funnel, immediately and fully vibrating, fully transferring the 2-hydroxy acridone into the added hot water solvent, and then standing the separating funnel. Separating liquid after the liquid is layered, taking a water layer, discarding an organic layer, standing the water layer, standing for cooling, and carrying out suction filtration to obtain filter residues, namely crude 2-hydroxy acridone;
(7) Recrystallizing the crude 2-hydroxy acridone with ethanol, precipitating, suction filtering to obtain high purity 2-hydroxy acridone, drying, weighing to obtain high purity 2-hydroxy acridone with mass of 3.80g, and calculating the yield of 90.1% according to the above yield formula.
The reaction vessel used in the present invention is not limited to a beaker, and other reaction vessels may be used, and preferably a glass reaction vessel is used, and the reaction and separation vessels used in the foregoing examples should not be construed as limiting the present invention.
The foregoing is merely an embodiment of the present invention, and the present invention is not limited in any way, and may have other embodiments according to the above structures and functions, which are not listed. Therefore, any simple modification, equivalent variation and modification of the above embodiments according to the technical substance of the present invention without departing from the scope of the technical solution of the present invention will still fall within the scope of the technical solution of the present invention.
Claims (7)
1. The method for rapidly synthesizing 2-hydroxy acridone by one-pot ultrasonic assistance is characterized by comprising the following steps of:
(1) Placing a certain amount of 2-bromobenzoic acid into a beaker, adding DMF solvent, and magnetically stirring to dissolve the 2-bromobenzoic acid to obtain solution A for later use;
(2) Placing a certain amount of p-methoxyaniline into a new beaker, adding DMF solvent into the beaker, and magnetically stirring to dissolve the p-methoxyaniline to obtain solution B for later use;
(3) Putting a certain amount of copper powder into a round-bottom flask, slowly pouring the solution A in the step (1) and the solution B in the step (2) into the round-bottom flask to obtain a mixed material for later use; wherein the mass of the copper powder is 2-5% of the mass of the 2-bromobenzoic acid;
(4) Placing the round-bottom flask filled with the mixed material in the step (3) in an ultrasonic reactor, adopting ultrasonic-assisted reaction, and naturally cooling to room temperature after the reaction is finished;
(5) Distilling the cooled material in the step (4) under reduced pressure and recovering excessive p-methoxyaniline;
(6) Transferring the residual liquid after the reduced pressure distillation in the step (5) into a separating funnel, adding hot water into the separating funnel, sufficiently oscillating to enable 2-hydroxy acridone to be sufficiently transferred into the hot water, standing the separating funnel, separating liquid after the liquid is layered, discarding an organic layer, taking a water layer, standing the obtained water layer, naturally cooling, and carrying out suction filtration to obtain filter residues, namely crude 2-hydroxy acridone;
(7) And recrystallizing the crude 2-hydroxy acridone with ethanol to obtain high-purity 2-hydroxy acridone.
2. The method for rapidly synthesizing 2-hydroxy acridone by one-pot ultrasonic assistance according to claim 1, wherein the molar ratio of the p-methoxyaniline to the 2-bromobenzoic acid is (1-1.2): 1.
3. The method for rapidly synthesizing 2-hydroxy acridone by one-pot ultrasonic assistance according to claim 1, wherein the volume ratio of the mass of 2-bromobenzoic acid to DMF in the step (1) is 1g (10-15 ml).
4. The method for rapidly synthesizing 2-hydroxy acridone by one-pot ultrasonic assistance according to claim 1, wherein the volume ratio of the mass of the p-methoxy aniline to the DMF in the step (2) is 1g (20-25 ml).
5. The method for ultrasonic-assisted rapid synthesis of 2-hydroxy acridone by one-pot method according to any one of claims 1-4, wherein the conditions of the ultrasonic-assisted reaction in step (4) are as follows: the ultrasonic frequency is 60-65KHz, the power is 400W, the reaction temperature is 50 ℃, and the reaction time is 45-60min.
6. The method for ultrasonic-assisted rapid synthesis of 2-hydroxy acridone by one-pot method according to claim 1 or 3, wherein the temperature of hot water added in the separating funnel of the step (5) is 50+/-5 ℃, and the adding volume of the hot water is 2-3 times of the volume of DMF in the step (1).
7. The method for ultrasonic-assisted rapid synthesis of 2-hydroxy acridone by one-pot method according to claim 1, wherein the molar yield of the finally prepared high-purity 2-hydroxy acridone is more than 85%.
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