CN103570520A - Benzoquinones compound, preparation method and application thereof - Google Patents
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- C07C50/00—Quinones
- C07C50/24—Quinones containing halogen
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- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/11—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by reactions increasing the number of carbon atoms
- C07C37/16—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by reactions increasing the number of carbon atoms by condensation involving hydroxy groups of phenols or alcohols or the ether or mineral ester group derived therefrom
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- C07C46/02—Preparation of quinones by oxidation giving rise to quinoid structures
- C07C46/06—Preparation of quinones by oxidation giving rise to quinoid structures of at least one hydroxy group on a six-membered aromatic ring
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- C07C2601/14—The ring being saturated
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- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
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Abstract
The invention discloses a benzoquinones compound, a preparation method and application thereof, and belongs to the drug synthesis field. The method comprises the following steps: condensing alpha-naphthol and 4-(4-chlorophenyl)cyclohexanol under acid catalysis to obtain 2-(4-(4-chlorophenyl)cyclohexyl)-1-naphthol (formula IV), oxidizing the compound represented by formula IV to obtain 2-(4-(4-chlorophenyl)cyclohexyl)-1,4-naphthoquinone (formula III), enabling the compound represented by the formula III to react with bromine in additive reaction to obtain 2,3-dibromo-2-(4-(4-chlorophenyl)cyclohexyl)-1,4-naphthoquinone (formula I), releasing a molecule of hydrogen bromide to obtain 3-bromo-2-(4-(4-chlorophenyl)cyclohexyl)-1,4-naphthoquinone (formula II). The method further discloses a method for preparing atovaquone by using the compound, the synthesis method is simple, the AgNO3 can be prevented from using, and the total yield is high.
Description
Technical field
The present invention relates to medicine synthetic field, specifically a kind of benzoquinone compound, its preparation method and application thereof.
Background technology
Quinones is a class at distributed in nature compound widely, and it comprises quinones and easily changes the compound of quinones character into.
From structure, quinones can be divided into benzoquinones, and naphthoquinones and anthraquinone have many-sided physiologically active, as antidiarrheal, antibiotic, diuresis and hemostasis etc., also has some quinoness to have the effects such as anticancer, antiviral, spasmolysis is relievingd asthma.Although disclose the preparation method of some quinoness, particularly benzoquinone compound in prior art, commonly used expensive catalyzer in preparation process, as AgNO
3deng, production cost is higher.
Atovaquone (Atovaquone) is a kind of homologue of ubiquinone, the trouble that is applicable to tolerate SMZ-TMP is slightly to patient's AIDS of moderate Ka Shi pneumonia oral administration, but also it is active to show certain anti-malarial, its chemistry 2-(trans-4-(4-chloro-phenyl-) cyclohexyl) by name-3-hydroxyl-1,4-naphthalenedione, chemical structure is suc as formula shown in (1)
Formula (1)
In prior art, the main synthetic atovaquone of following several method that adopts:
⑴
The main reference of this method is US 5053432 and EP 0362996, and the main synthesis technique that above-mentioned technique is current atovaquone is generated by the chloro-1,4-naphthoquinone of 2-(chlorinated naphthoquinone) and the condensation reaction of 4-(4-chloro-phenyl-)-cyclohexyl-1-formic acid.Reaction be take acetonitrile as solvent, under Silver Nitrate exists, uses ammonium persulphate oxidative decarboxylation, generates the chloro-3-of (3S)-2-(4-(4-chloro-phenyl-) cyclohexyl) Isosorbide-5-Nitrae-naphthalenedione.Under alkaline condition, hydrolysis obtains final product (3S)-2-hydroxyl-3-(4-(4-chloro-phenyl-) cyclohexyl) Isosorbide-5-Nitrae-naphthalenedione, i.e. atovaquone.The main drawback of this route is that the solvent that oxidative decarboxylation is used is acetonitrile, acetonitrile is to 2-chloro-1, the solubleness of 4-naphthoquinones (chlorinated naphthoquinone), 4-(4-chloro-phenyl-)-cyclohexyl-1-formic acid and Silver Nitrate has very big-difference, and along with adding of ammonium persulfate solution, noted phase separation phenomena is very obvious.And this reaction side reaction is more, reaction produces a lot of impurity, causes that product yield is on the low side only 20% left and right.
⑵
The main referenced patent of this method is WO 2009/122432 A2, above-mentioned technique is with 2,3-dichlone and 4-(4-chloro-phenyl-) cyclohexylenedinitrilotetraacetic acid is starting raw material, under the catalytic condition of Silver Nitrate and ammonium persulphate, there is condensation reaction, then, be hydrolyzed to obtain the finished product under the effect of alkali, the major advantage of this technique is yield ratio method (1) height, condensation reaction yield is up to 40%, and hydrolysis reaction yield reaches 95.5%.But this method has been used AgNO equally
3and ammonium persulphate, production cost is higher, bad to environmental influence.
In above-mentioned two kinds of methods, all used expensive AgNO
3, not only cost is high and productive rate is all very low, and meanwhile, last handling process also can produce very havoc to environment.
Summary of the invention
Technical assignment of the present invention is for above-mentioned the deficiencies in the prior art, and a kind of benzoquinone compound that can be used for producing atovaquone is provided.
Second technical assignment of the present invention is to provide the preparation method of above-mentioned benzoquinone compound.
The 3rd technical assignment of the present invention is to provide the application of above-mentioned benzoquinone compound.
Technical assignment of the present invention is realized in the following manner: have formula
the benzoquinone compound of chemical structure, called after: 2,3-dibromo 2-(4-(4-chloro-phenyl-) cyclohexyl)-1,4-naphthoquinone.
There is formula
the preferred following methods of benzoquinone compound of chemical structure makes: the condensation under acid catalysis of naphthyl alcohol and 4-(4-chloro-phenyl-) hexalin obtains 2-(4-(4-chloro-phenyl-) cyclohexyl)-1-naphthols (formula IV); Compound shown in formula IV, through oxidation, obtains 2-(4-(4-chloro-phenyl-) cyclohexyl)-1,4-naphthoquinone (formula III).Compound shown in formula III and bromine generation addition reaction, obtain the bromo-2-of 2,3-bis-(4-(4-chloro-phenyl-) cyclohexyl)-1,4-naphthoquinone (formula I).
Synthetic route equation is as follows:
Above-mentioned preparation method comprises the following steps:
A, preparation 2-(4-(4-chloro-phenyl-) cyclohexyl)-1-naphthols (formula IV)
By naphthyl alcohol, 4-(4-chloro-phenyl-) hexalin and solvent, under 120 ~ 150 ℃, acid catalyst catalytic condition, react complete to raw material reaction, obtain compound shown in formula IV;
Described naphthyl alcohol and 4-(4-chloro-phenyl-) hexalin mol ratio is 1:1 ~ 4;
The mol ratio of described acid catalyst and two raw materials (naphthyl alcohol, 4-(4-chloro-phenyl-) hexalin) sum is 0.1 ~ 1:1;
B, prepare the bromo-2-of 2,3-bis-(4-(4-chloro-phenyl-) cyclohexyl)-1,4-naphthoquinone (formula I)
Under acid catalysis, with compound shown in oxygenant oxidation-type IV, obtain compound shown in formula III; Bromine simple substance reacts and obtains compound shown in formula I with compound shown in formula III.
Further:
In steps A, described solvent is preferably benzene, toluene or chlorobenzene; Described acid catalyst is preferably toluenesulphonic acids, trifluoroacetic acid, acetic acid, the vitriol oil or phosphoric acid.
Step B can complete in two steps, also can one completes, and all can reach good effect.
While completing in two steps, its detailed process is respectively:
A, compound shown in steps A gained formula IV is added in solvent, under appropriate amount of acid catalyst action, with oxygenant oxidation, after completion of the reaction, obtain compound shown in formula III;
Described solvent is preferably acetone, acetonitrile or tetrahydrofuran (THF);
Shown in described acid catalyst and formula IV, the mol ratio of compound is 1 ~ 5:1;
Shown in described oxygenant and formula IV, the mol ratio of compound is 1 ~ 20:1;
The temperature of reaction of described oxidizing reaction is 60 ~ 90 ℃;
B, a certain amount of bromine simple substance is added shown in the formula III being dissolved in solvent in compound, react complete to raw material reaction, obtain compound shown in formula I;
Shown in described bromine simple substance and formula III, the mol ratio of compound is 1 ~ 5:1;
Described solvent is preferably tetracol phenixin, dimethyl sulfoxide (DMSO), dimethyl formamide, acetic acid or acetonitrile.
When one step completes, its detailed process is:
Compound shown in steps A gained formula IV and appropriate bromine simple substance are added in solvent, and under appropriate amount of acid catalyst action, with oxygenant oxidation, back flow reaction, after completion of the reaction, purifies and obtains compound shown in formula I;
Shown in described bromine simple substance and formula IV, the mol ratio of compound is 1 ~ 5:1;
Shown in described acid catalyst and formula IV, the mol ratio of compound is 1 ~ 5:1;
Shown in described oxygenant and formula IV, the mol ratio of compound is 1 ~ 20:1;
The temperature of reaction of described oxidizing reaction is 60 ~ 120 ℃;
Described solvent is tetracol phenixin, dimethyl sulfoxide (DMSO), dimethyl formamide, acetic acid or acetonitrile.
In step B, described oxygenant is preferably hydrogen peroxide, chromic oxide, cerous sulfate, ceric ammonium nitrate, potassium permanganate, Manganse Dioxide or dichromate;
Described acid catalyst is preferably concentrated hydrochloric acid, Glacial acetic acid or the vitriol oil.
The benzoquinone compound with formula II chemical structure, by formula
the hydrogen bromide that the benzoquinone compound of chemical structure is sloughed a part makes.The bromo-2-of called after: 3-(4-(4-chloro-phenyl-) cyclohexyl)-1,4-naphthoquinone (formula II).
Synthetic route equation is as follows:
The preparation method of the benzoquinone compound of formula II chemical structure is:
By formula
the benzoquinone compound of chemical structure is dissolved in solvent, under 60 ~ 90 ℃ of conditions, reacts 2 ~ 24h, is washed to and occurs precipitation, obtains compound shown in formula II;
Described solvent is preferably dimethyl sulfoxide (DMSO), dimethyl formamide, acetic acid or acetonitrile.
Or:
By formula
the benzoquinone compound of chemical structure is dissolved in solvent, adds appropriate sodium acetate to make catalyzer, and back flow reaction is to reacting completely, the compound shown in formula II of purifying to obtain;
Described solvent is preferably dimethyl sulfoxide (DMSO), dimethyl formamide, acetic acid or acetonitrile;
Described in described sodium acetate and claim 1, the mol ratio of benzoquinone compound is 1 ~ 10:1.
The benzoquinone compound of above-mentioned formula II chemical structure can be used for preparing atovaquone, preparation method comprises: under the condition existing at alkali, using alcohol as solvent, the benzoquinone compound generation hydrolysis reaction of formula II chemical structure, after having reacted, washing, can obtain 3-hydroxyl-2-(4-(4-chloro-phenyl-) cyclohexyl)-1,4-naphthoquinone; The mol ratio of the bromo-2-of described alkali and 3-(4-(4-chloro-phenyl-) cyclohexyl)-1,4-naphthoquinone is 1 ~ 20:1.Synthetic route is as follows:
Described alkali is preferably sodium hydroxide, potassium hydroxide, hydrated barta, lithium hydroxide, carbonate or supercarbonate;
Described alcohol is preferably one or more the mixture in methyl alcohol, ethanol, n-propyl alcohol, Virahol, propyl carbinol or isopropylcarbinol.
Benzoquinone compound of the present invention, its preparation method and application thereof compared with prior art have following outstanding beneficial effect:
(1) in benzoquinone compound preparation process, by product is few, and cost is low;
(2), while preparing atovaquone with this compound, can avoid using expensive catalytic reagent AgNO
3, become
This is cheap and do not pollute the environment, can better be for industrial production; Total recovery is higher than existing synthesis technique.
Embodiment
With specific embodiment, benzoquinone compound of the present invention, its preparation method and application thereof are described in detail below.
the embodiment mono-preparation bromo-2-of 2,3-bis-(4-(4-chloro-phenyl-) cyclohexyl)-1,4-naphthoquinone, 3-bromine 2-(4-(4-chloro-phenyl-) cyclohexyl)-1,4-naphthoquinone
The preparation of A, 2-(4-(4-chloro-phenyl-) cyclohexyl)-1-naphthols (formula IV)
Under nitrogen protection; by 4-(4-chloro-phenyl-) hexalin 2.9g, naphthyl alcohol 2g, tosic acid 2.63g adds in 30ml toluene; 140 ℃ of back flow reaction 3h; TLC monitoring reaction is carried out, and after reacting completely, organic phase washes with water; phase-splitting dewaters; organic phase anhydrous sodium sulfate drying, concentrating under reduced pressure, crystallization obtains 2-(4-(4-chloro-phenyl-) cyclohexyl)-1-naphthols.
B, 2, the preparation of the bromo-2-of 3-bis-(4-(4-chloro-phenyl-) cyclohexyl)-1,4-naphthoquinone (formula I)
(a), the preparation of 2-(4-(4-chloro-phenyl-) cyclohexyl)-1,4-naphthoquinone (formula III)
Add 2-(4-(4-chloro-phenyl-) cyclohexyl)-1-naphthols 2.98g in 15ml acetonitrile, then drip successively 4ml concentrated hydrochloric acid (38%, v/v), 16ml hydrogen peroxide (30%, v/v), stirring reaction 3h at 100 ℃, TLC detection reaction progress, after reacting completely, concentrating under reduced pressure, adds 20ml chloroform, and organic layer washes with water, separate organic layer, condensing crystal, obtains 2-(4-(4-chloro-phenyl-) cyclohexyl)-1,4-naphthoquinone.
(b), 2, the preparation of the bromo-2-of 3-bis-(4-(4-chloro-phenyl-) cyclohexyl)-1,4-naphthoquinone (formula I)
The bromine simple substance of 60ul is added in the acetic acid of 1ml, the acetic acid solution of bromine is dropped to 2-(4-(4-chloro-phenyl-) cyclohexyl)-1 in 15min, in the mixed system that 4-naphthoquinones 2.24g and acetic acid 5ml form, stirring at room 45min, pours into the reaction solution obtaining in frozen water, has Precipitation, suction filtration, obtain the bromo-2-of 2,3-bis-(4-(4-chloro-phenyl-) cyclohexyl)-1,4-naphthoquinone.
The preparation of the bromo-2-of C, 3-(4-(4-chloro-phenyl-) cyclohexyl)-1,4-naphthoquinone (formula II)
The bromo-2-of 2,3-bis-(4-(4-chloro-phenyl-) cyclohexyl)-1,4-naphthoquinone 5g is dissolved in 25mlDMSO, 60 ℃ of reaction 2h, TLC detection reaction is carried out, after reacting completely, be washed to and occur precipitation, obtain the bromo-2-of 3-(4-(4-chloro-phenyl-) cyclohexyl)-1,4-naphthoquinone.
embodiment bis-preparation 2,3-dibromo 2-(4-(4-chloro-phenyl-) cyclohexyl)-1,4-naphthoquinones, 3-bromine 2-(4-(4-chloro-phenyl-) cyclohexyl)-1,4-naphthoquinone
The preparation of A, 2-(4-(4-chloro-phenyl-) cyclohexyl)-1-naphthols (formula IV)
In the there-necked flask of 100ml, add chlorobenzene 30ml, naphthyl alcohol 2g, 4-(4-chloro-phenyl-) hexalin 4.65g and tosic acid 0.8g, back flow reaction 3h, TLC monitors reaction, react complete, concentrating under reduced pressure, adds chloroform extraction, washing, separate organic layer, boil off solvent, obtain product 2-(4-(4-chloro-phenyl-) cyclohexyl)-1-naphthols.
B, 2, the preparation of 3-dibromo 2-(4-(4-chloro-phenyl-) cyclohexyl)-1,4-naphthoquinone (formula I)
In 30ml tetracol phenixin, add 2-(4-(4-chloro-phenyl-) cyclohexyl)-1-naphthols 3.36g, Br
21.6g, 30% superoxol 1.2ml, 98% vitriol oil 0.6ml, reaction solution backflow 20min, concentrate and be cooled to 0 ℃, after suction filtration, retain solid, in filtrate, add suitable quantity of water, by extracted with diethyl ether, concentrate to obtain thick product, the thick product of two portions merges recrystallization and obtains the bromo-2-of 2,3-bis-(4-(4-chloro-phenyl-) cyclohexyl)-1,4-naphthoquinone.
The preparation of the bromo-2-of C, 3-(4-(4-chloro-phenyl-) cyclohexyl)-1,4-naphthoquinone (formula II)
By 2,3-dibromo 2-(4-(4-chloro-phenyl-) cyclohexyl)-1,4-naphthoquinone 0.3g is dissolved in the acetic acid of 10ml, adds the sodium acetate of 0.2g, back flow reaction 1h, TLC monitoring, adds 5ml water in reaction solution, ethyl acetate extraction, anhydrous sodium sulfate drying, concentrating under reduced pressure, obtains the bromo-2-of 3-(4-(4-chloro-phenyl-) cyclohexyl)-1,4-naphthoquinone.
embodiment tri-prepares atovaquone
By the bromo-2-of 3-(4-(4-chloro-phenyl-) cyclohexyl)-1,4-naphthoquinones 2.145g and sodium hydroxide 1.6g are dissolved in 65ml methyl alcohol, back flow reaction, TLC detection reaction progress, reacts complete, adjust pH2 ~ 3, the concentrated methyl alcohol of removing, with ethyl acetate extraction, vacuum concentration, low temperature crystallization obtains target compound atovaquone (3-hydroxyl-2-(4-(4-chloro-phenyl-) cyclohexyl)-1,4-naphthoquinone).
embodiment tetra-prepares atovaquone
By the bromo-2-of 3-(4-(4-chloro-phenyl-) cyclohexyl)-1,4-naphthoquinones 2.2g and sodium carbonate 3.18g join in 45ml Virahol, reflux, react complete, filtration under diminished pressure, the concentrated Virahol of removing, with ethyl acetate, extract, vacuum concentration, low temperature crystallization obtains target compound atovaquone (3-hydroxyl-2-(4-(4-chloro-phenyl-) cyclohexyl)-1,4-naphthoquinone).
Claims (13)
1. there is formula
the benzoquinone compound of chemical structure,
2. the preparation method of benzoquinone compound described in claim 1, is characterized in that, the condensation under acid catalysis of naphthyl alcohol and 4-(4-chloro-phenyl-) hexalin obtains 2-(4-(4-chloro-phenyl-) cyclohexyl)-1-naphthols (formula IV); Compound shown in formula IV, through oxidation, obtains 2-(4-(4-chloro-phenyl-) cyclohexyl)-1,4-naphthoquinone (formula III); Compound shown in formula III and bromine generation addition reaction, obtain the bromo-2-of 2,3-bis-(4-(4-chloro-phenyl-) cyclohexyl)-1,4-naphthoquinone (formula I).
3. preparation method according to claim 2, is characterized in that comprising the following steps:
A, preparation 2-(4-(4-chloro-phenyl-) cyclohexyl)-1-naphthols (formula IV)
By naphthyl alcohol, 4-(4-chloro-phenyl-) hexalin and solvent, under 120 ~ 150 ℃, acid catalyst catalytic condition, react complete to raw material reaction, obtain compound shown in formula IV;
Described naphthyl alcohol and 4-(4-chloro-phenyl-) hexalin mol ratio is 1:1 ~ 4;
The mol ratio of described acid catalyst and two raw material sums is 0.1 ~ 1:1;
B, prepare the bromo-2-of 2,3-bis-(4-(4-chloro-phenyl-) cyclohexyl)-1,4-naphthoquinone (formula I);
Under acid catalysis, with compound shown in oxygenant oxidation-type IV, obtain compound shown in formula III; Bromine simple substance reacts and obtains compound shown in formula I with compound shown in formula III.
4. preparation method according to claim 3, is characterized in that: in steps A,
Described solvent is benzene, toluene or chlorobenzene;
Described acid catalyst is toluenesulphonic acids, trifluoroacetic acid, acetic acid, the vitriol oil or phosphoric acid.
5. preparation method according to claim 3, is characterized in that, the detailed process of step B is:
A, compound shown in steps A gained formula IV is added in solvent, under appropriate amount of acid catalyst action, with oxygenant oxidation, after completion of the reaction, obtain compound shown in formula III;
Described solvent is acetone, acetonitrile or tetrahydrofuran (THF);
Shown in described acid catalyst and formula IV, the mol ratio of compound is 1 ~ 5:1;
Shown in described oxygenant and formula IV, the mol ratio of compound is 1 ~ 20:1;
The temperature of reaction of described oxidizing reaction is 60 ~ 90 ℃;
B, a certain amount of bromine simple substance is added shown in the formula III being dissolved in solvent in compound, react complete to raw material reaction, obtain compound shown in formula I;
Shown in described bromine simple substance and formula III, the mol ratio of compound is 1 ~ 5:1;
Described solvent is tetracol phenixin, dimethyl sulfoxide (DMSO), dimethyl formamide, acetic acid or acetonitrile.
6. preparation method according to claim 3, is characterized in that, the detailed process of step B is:
Compound shown in steps A gained formula IV and appropriate bromine simple substance are added in solvent, and under appropriate amount of acid catalyst action, with oxygenant oxidation, back flow reaction, after completion of the reaction, purifies and obtains compound shown in formula I;
Shown in described bromine simple substance and formula IV, the mol ratio of compound is 1 ~ 5:1;
Shown in described acid catalyst and formula IV, the mol ratio of compound is 1 ~ 5:1;
Shown in described oxygenant and formula IV, the mol ratio of compound is 1 ~ 20:1;
The temperature of reaction of described oxidizing reaction is 60 ~ 120 ℃;
Described solvent is tetracol phenixin, dimethyl sulfoxide (DMSO), dimethyl formamide, acetic acid or acetonitrile.
7. according to the preparation method described in claim 5 or 6, it is characterized in that:
Described oxygenant is hydrogen peroxide, chromic oxide, cerous sulfate, ceric ammonium nitrate, potassium permanganate, Manganse Dioxide or dichromate;
Described acid catalyst is concentrated hydrochloric acid, Glacial acetic acid or the vitriol oil.
8. the benzoquinone compound with formula II chemical structure,
The hydrogen bromide of being sloughed a part by benzoquinone compound described in claim 1 makes.
9. the preparation method of benzoquinone compound described in claim 8, is characterized in that, benzoquinone compound described in claim 1 is dissolved in solvent, under 60 ~ 90 ℃ of conditions, reacts 2 ~ 24h, is washed to and occurs precipitation, obtains compound shown in formula II;
Described solvent is dimethyl sulfoxide (DMSO), dimethyl formamide, acetic acid or acetonitrile.
10. the preparation method of benzoquinone compound described in claim 8, is characterized in that, benzoquinone compound described in claim 1 is dissolved in solvent, adds appropriate sodium acetate to make catalyzer, and back flow reaction is to reacting completely, the compound shown in formula II of purifying to obtain;
Described solvent is dimethyl sulfoxide (DMSO), dimethyl formamide, acetic acid or acetonitrile;
Described in described sodium acetate and claim 1, the mol ratio of benzoquinone compound is 1 ~ 10:1.
The application of the benzoquinone compound of 11. formula II chemical structures in preparing atovaquone.
12. application according to claim 11, it is characterized in that: under the condition existing at alkali, using alcohol as solvent, the benzoquinone compound generation back flow reaction of formula II chemical structure, after having reacted, washing, can obtain 3-hydroxyl-2-(4-(4-chloro-phenyl-) cyclohexyl)-1,4-naphthoquinone;
Shown in described alkali and formula II, the mol ratio of compound is 1 ~ 20:1.
13. application according to claim 12, is characterized in that:
Described alkali is sodium hydroxide, potassium hydroxide, hydrated barta, lithium hydroxide, carbonate or supercarbonate;
Described alcohol is one or more the mixture in methyl alcohol, ethanol, n-propyl alcohol, Virahol, propyl carbinol or isopropylcarbinol.
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| CN109876849A (en) * | 2017-12-06 | 2019-06-14 | 中国科学院大连化学物理研究所 | A kind of naphthalene liquid phase oxidation preparation 1,4- naphthoquinones catalyst and its preparation method and application |
| CN110734368A (en) * | 2018-07-19 | 2020-01-31 | 新发药业有限公司 | Preparation method of buparvaquone |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109876849A (en) * | 2017-12-06 | 2019-06-14 | 中国科学院大连化学物理研究所 | A kind of naphthalene liquid phase oxidation preparation 1,4- naphthoquinones catalyst and its preparation method and application |
| CN109876849B (en) * | 2017-12-06 | 2020-08-11 | 中国科学院大连化学物理研究所 | 1, 4-naphthoquinone catalyst prepared by liquid-phase oxidation of naphthalene and preparation method and application thereof |
| CN110734368A (en) * | 2018-07-19 | 2020-01-31 | 新发药业有限公司 | Preparation method of buparvaquone |
| CN110734368B (en) * | 2018-07-19 | 2022-08-12 | 新发药业有限公司 | Preparation method of buparvaquone |
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