CN108314615A - A kind of preparation method of high-purity Hinokitiol - Google Patents

A kind of preparation method of high-purity Hinokitiol Download PDF

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CN108314615A
CN108314615A CN201810032873.9A CN201810032873A CN108314615A CN 108314615 A CN108314615 A CN 108314615A CN 201810032873 A CN201810032873 A CN 201810032873A CN 108314615 A CN108314615 A CN 108314615A
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solution
hinokitiol
isopropylcyclopentadienes
added
isopropylcyclopentadiene
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李伟
祁文彩
徐桂清
毛龙飞
姜玉钦
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Henan Normal University
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Henan Normal University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/65—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by splitting-off hydrogen atoms or functional groups; by hydrogenolysis of functional groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C1/00—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon
    • C07C1/32—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from compounds containing hetero-atoms other than or in addition to oxygen or halogen
    • C07C1/325—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from compounds containing hetero-atoms other than or in addition to oxygen or halogen the hetero-atom being a metal atom
    • C07C1/328—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from compounds containing hetero-atoms other than or in addition to oxygen or halogen the hetero-atom being a metal atom the hetero-atom being an alkali metal atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/45—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation
    • C07C45/455—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation with carboxylic acids or their derivatives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C5/00—Preparation of hydrocarbons from hydrocarbons containing the same number of carbon atoms
    • C07C5/22—Preparation of hydrocarbons from hydrocarbons containing the same number of carbon atoms by isomerisation
    • C07C5/23—Rearrangement of carbon-to-carbon unsaturated bonds
    • C07C5/25—Migration of carbon-to-carbon double bonds
    • C07C5/2506—Catalytic processes
    • C07C5/2562—Catalytic processes with hydrides or organic compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2531/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • C07C2531/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • C07C2531/04—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides containing carboxylic acids or their salts
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/584—Recycling of catalysts

Abstract

The invention discloses a kind of preparation methods of high-purity Hinokitiol, the isopropylcyclopentadiene of the isomers containing there are many is obtained by the reaction with isopropyl bromide after the activated reagent activation of cyclopentadiene, then carries out isomerization reaction under the action of isomers reforming catalyst and obtains 1 isopropylcyclopentadiene；1 isopropylcyclopentadiene reacts to obtain 1 isopropylcyclopentadiene and 4,4 dichloro ring fourth, 5 ketone with dichloro cyclic ketones；1 isopropylcyclopentadiene and 4,4 dichloro ring fourth, 5 ketone are heated to reflux generation ring expansion with triethylamine and obtain target product Hinokitiol.Raw material used in the present invention is cheap and easy to get, and significantly reduces the generation of by-product 2 isopropylcyclopentadiene and 5 isopropylcyclopentadienes in step A by the use of isomers reforming catalyst, improves the yield of product, and Ru (Ac)3ZSM still maintains preferable catalytic activity 5 reusable four times；Reaction solution is adjusted by glacial acetic acid in step B, effectively prevents the appearance of diketone by-product.

Description

A kind of preparation method of high-purity Hinokitiol
Technical field
The invention belongs to the synthesis technical fields of medicine intermediate, and in particular to a kind of preparation side of high-purity Hinokitiol Method.
Background technology
Hinokitiol (chamenol, Hinokitol) chemical name is -2,4,6- cycloheptyls three of 2- hydroxyls -4- (1- Methylethyls) Alkene -1- ketone, molecular formula C10H12O2, molecular weight 164.2, it is in 1948 by the scientist Anderson of Japan from Taiwan A kind of native compound of the monoterpenes with tall and erect phenolic ketone skeleton extracted in the trunk of Japan cypress, belongs to tropolone compounds of group, tool There are good antibiotic property, moisture retention and pest Repellency effect, be the plant component of high security, can be used as antiseptic, insect-proof agent. Hinokitiol is the main component of Taiwan Japan cypress essential oil, has relatively broad bioactivity, has the sterilizing ability of strength, to general The minimal inhibitory concentration of bacterium is 10~100ppm, fragrant and is worked well, can kill bacterium in air, fungi, It prevents pest infestation human body, inhibit mankind pathogeny bacterium.The productions such as production shower cream, cosmetics, medicine, agricultural are had been used at present Product.For Hinokitiol to inhibiting staphylococcus aureus (MRSA) to have surprising effect, which is often stored in human skin, respiratory tract, draws Play the skin infections such as septicemia, peritonitis, food poisoning and boil purulence ulcer.In addition, prevention of the Hinokitiol in terms of soil-borne disease It is upper that there is effect outstanding.
Because natural resources are limited, recent domestic researches and develops the synthetic technology of Hinokitiol, existing synthetic route master energetically Have：(1) it is synthesized from methoxyl group cycloheptatriene through isopropyl tropone and amino isopropyl tropone；(2) from perfume (or spice) Celery ketone is synthesized through six-step processes such as epoxidation, acetalations；(3) transformed at hydroxyl from isopropyl pentylcyclohexanone or cryptone Isopropyl cycloheptanone, then the synthesis of oxidized, bromination, dehydrobromination is made in base nitrile, two steps；(4) bromo tropone and one kind Organic matter reacts, and then catalytic hydrogenation synthesizes.But above-mentioned four kinds of synthesis technologies are relatively complicated, some target product yields Relatively low, some target product purity are relatively low, are more also that raw material is relatively difficult to obtain, therefore, above-mentioned four kinds of conjunctions Industrialized production actually can not be preferably realized at technique.
Invention content
The technical problem to be solved by the present invention is to provide a kind of simple for process, of low cost and be easily industrialized production High-purity Hinokitiol preparation method.
The present invention adopts the following technical scheme that solve above-mentioned technical problem, a kind of preparation method of high-purity Hinokitiol, It is characterized in that the specific steps are：
Step A, it is obtained by the reaction with isopropyl bromide containing there are many isopropyls of isomers after the activated reagent activation of cyclopentadiene Butylcyclopentadiene, then carry out isomerization reaction under the action of isomers reforming catalyst and obtain 1- isopropylcyclopentadienes, Middle activating reagent is metallic sodium, lithium metal, sodium hydride or hydrofining, and isomers reforming catalyst is RuCl3·3H2O、Ru (acac)3、Ru(Ac)3- ZSM-5 or Ru (NO) (NO3)3；
Step B, 1- isopropylcyclopentadienes react to obtain 1- isopropylcyclopentadienes and 4,4- bis- with dichloro cyclic ketones Chlorine ring fourth 5- ketone；
Step C, simultaneously 4,4- dichloro ring fourth 5- ketone is heated to reflux generation ring expansion to 1- isopropylcyclopentadienes with triethylamine Obtain target product Hinokitiol.
Further preferably, the detailed process of step A is：Activating reagent is distributed to tetrahydrofuran under inert gas protection In, cyclopentadiene is added, 1h is stirred to react in 30 DEG C, dimethyl sulfoxide (DMSO) is added after boiling off tetrahydrofuran in decompression, after obtaining activation Cyclopentadiene dimethylsulfide complex solution；N-hexane is added into solution again, is cooled to 0 DEG C of dropwise addition isopropyl bromide, The temperature of charging present invention liquid is no more than 5 DEG C, and temperature when adding is no more than 10 DEG C, then hydrochloric acid solution and n-hexane is added dropwise, It is stirred to react in 10 DEG C, standing separation organic layer obtains the solution containing isopropylcyclopentadiene after reaction；Isomers is turned Change catalyst to be added in the solution containing isopropylcyclopentadiene, and is stirred in 20 DEG C and carry out isomerization reactions, filtering reacting liquid, 1- isopropylcyclopentadienes are obtained after concentration.
Further preferably, the molar ratio of cyclopentadiene and activating reagent described in step A is 1:1~3；Cyclopentadiene The mass ratio that feeds intake with dimethyl sulfoxide (DMSO) is 1:1.25；The molar ratio of cyclopentadiene and isopropyl bromide is 1:1.5~2, it is excellent It is selected as 1:1.7；The molar ratio of cyclopentadiene and HCl are 1:0.8~1.2.
Further preferably, the detailed process of step B is：1- isopropylcyclopentadienes are added in n-hexane, are kept molten Liquid temperature is added dichloroacetyl chloride and keeps solution temperature at 0 DEG C, then triethylamine is added dropwise, ice second is added after being added dropwise at 0 DEG C Acid, the pH for adjusting reaction solution is 5~6, boils off vacuum distillation after solvent and obtains 1- isopropylcyclopentadienes and 4,4- dichloro ring fourths 5- ketone.
Further preferably, the molar ratio of isopropylcyclopentadiene and dichloroacetyl chloride described in step B is 1:1~ 1.3, preferably 1:1.15.
Further preferably, the detailed process of step C is：By 1- isopropylcyclopentadienes, simultaneously 4,4- dichloro ring fourth 5- ketone is dissolved in The in the mixed solvent of the tert-butyl alcohol, water and acetic acid is heated to reflux the lower dropwise addition triethylamine of stirring and carries out back flow reaction, adds postcooling extremely Room temperature, adds water, concentrated hydrochloric acid and n-hexane, stratification after stirring, and organic layer decompression is boiled off solvent, and to obtain Hinokitiol thick Hinokitiol crude product is evaporated under reduced pressure by product, and the master of 95 DEG C/1mm Hg is collected after 45~90 DEG C/1mm Hg distillate front-end volatiles Fraction obtains Hinokitiol, and Hinokitiol main distillate fraction is dissolved in recrystallization solution in 40 DEG C, cold with the rate of temperature fall of 1~2 DEG C/min But to 0 DEG C, crystallization is precipitated, filters, is washed with the acetone for being cooled to 0 DEG C, it is dry, obtain Hinokitiol crystallized product.
Further preferably, 1- isopropylcyclopentadienes described in step C and 4,4- dichloro ring fourth 5- ketone and acetic acid feed intake Molar ratio is 1:4~6, preferably 1:5；1- isopropylcyclopentadienes and 4,4- dichloro ring fourth 5- ketone and triethylamine feed intake mole Than being 1:6.
Further preferably, the recrystallization solution be acetone, isopropanol, hexamethylene, acetone and isopropanol mixed liquor or The volume ratio 1 of acetone and isopropanol in the mixed solution of the mixed liquor of acetone and hexamethylene, acetone and isopropanol:1, acetone and ring The volume ratio 1 of acetone and hexamethylene in the mixed solution of hexane:1.
The preparation method of high-purity Hinokitiol of the present invention, it is characterised in that the synthetic route of preparation process is：
Compared with the prior art, the present invention has the following advantages：Raw material used in the present invention is cheap and easy to get, and step A In by-product 2- isopropylcyclopentadienes and 5- isopropyls basic ring penta 2 significantly reduced by the use of isomers reforming catalyst The generation of alkene improves the yield of product, and Ru (Ac)3- ZSM-5 still maintains preferable catalysis for reusable four times and lives Property；Reaction solution is adjusted by glacial acetic acid in step B, effectively prevents the appearance of diketone by-product.
Specific implementation mode
The above of the present invention is described in further details by the following examples, but this should not be interpreted as to this The range for inventing above-mentioned theme is only limitted to embodiment below, and all technologies realized based on the above of the present invention belong to this hair Bright range.
Embodiment 1
Under nitrogen protection, metallic sodium 13.8g (0.6mol) is distributed in tetrahydrofuran 250g, cyclopentadiene is added 40g (0.6mol), maintaining reaction temperature stir 1h at 30 DEG C, and decompression is added dimethyl sulfoxide (DMSO) 50g after boiling off tetrahydrofuran, obtains The dimethylsulfide complex solution of cyclopentadienyl sodium；N-hexane 150g is added into solution again, is cooled to DEG C, in 50min The temperature of interior instillation isopropyl bromide 147g (1.2mol), charging present invention liquid is no more than 5 DEG C, and temperature when adding is no more than 10 DEG C, hydrochloric acid solution 60g (0.6mol) and n-hexane 150g is slowly added dropwise, is stirred to react in 10 DEG C, separation organic layer obtains containing 1- The solution of isopropylcyclopentadiene, GC analyze the mass ratio 1- isopropylcyclopentadienes of product and isomers:5- isopropyl basic rings Pentadiene:Isopropylcyclopentadiene=58.3 2-:26.8:14.9, Ru (Ac) will be added in this solution3In 20.0 after-ZSM-54g DEG C stirring carries out isomerization reaction 6h, and the mass ratio of GC analysis products and isomers becomes 1- isopropylcyclopentadienes:5- is different Propyl cyclopentadiene:Isopropylcyclopentadiene=97.9 2-:0.9:1.2, reaction solution is filtered, 1- isopropyls basic ring penta is obtained after concentration Diene 62.2g, yield 96%.
Embodiment 2
Under nitrogen protection, metallic sodium 41.4g (1.8mol) is distributed in tetrahydrofuran 250g, cyclopentadiene is added 40g (0.6mol), maintaining reaction temperature stir 1h at 30 DEG C, and decompression is added dimethyl sulfoxide (DMSO) 50g after boiling off tetrahydrofuran, obtains The dimethylsulfide complex solution of cyclopentadienyl sodium；N-hexane 150g is added into solution again, 0 DEG C is cooled to, in 50min The temperature of interior instillation isopropyl bromide 147g (1.2mol), charging present invention liquid is no more than 5 DEG C, and temperature when adding is no more than 10 DEG C, hydrochloric acid solution 180g (1.8mol) and n-hexane 150g is slowly added dropwise, is stirred to react in 10 DEG C, standing separation organic layer obtains The solution of the isopropylcyclopentadiene containing 1-, GC analyze the mass ratio 1- isopropylcyclopentadienes of product and isomers:5- isopropyls Butylcyclopentadiene:Isopropylcyclopentadiene=51.7 2-:29.4:18.9, Ru (Ac) will be added in this solution3After-ZSM-5 4g The mass ratio that isomerization reaction 6h, GC analysis product and isomers are carried out in 20.0 DEG C of stirrings becomes 1- isopropyls basic ring penta 2 Alkene:5- isopropylcyclopentadienes:Isopropylcyclopentadiene=98.5 2-:0.7:0.8, reaction solution is filtered, it is different to obtain 1- after concentration Propyl cyclopentadiene 58.9g, yield 91%.
Embodiment 3
Under nitrogen protection, lithium metal 6.3g (0.9mol) is distributed in tetrahydrofuran 250g, cyclopentadiene 40g is added (0.6mol), maintaining reaction temperature stir 1h at 30 DEG C, and decompression is added dimethyl sulfoxide (DMSO) 50g after boiling off tetrahydrofuran, obtains ring The dimethylsulfide complex solution of pentadienyl lithium；N-hexane 150g is added into solution again, 0 DEG C is cooled to, in 50min Isopropyl bromide 147g (1.2mol) is instilled, the temperature of charging present invention liquid is no more than 5 DEG C, and temperature when adding is no more than 10 DEG C, hydrochloric acid solution 90g (0.9mol) and n-hexane 150g is slowly added dropwise, is stirred to react in 10 DEG C, standing separation organic layer obtains The solution of the isopropylcyclopentadiene containing 1-, GC analyze the mass ratio 1- isopropylcyclopentadienes of product and isomers:5- isopropyls Butylcyclopentadiene:Isopropylcyclopentadiene=45.3 2-:37.1:17.6, Ru (Ac) will be added in this solution3After-ZSM-5 4g The mass ratio that isomerization reaction 6h, GC analysis product and isomers are carried out in 20.0 DEG C of stirrings becomes 1- isopropyls basic ring penta 2 Alkene:5- isopropylcyclopentadienes:Isopropylcyclopentadiene=96.3 2-:1.7:2.0, reaction solution is filtered, it is different to obtain 1- after concentration Propyl cyclopentadiene 59.6g, yield 92%.
Embodiment 4
Under nitrogen protection, the sodium hydride 24g (0.6mol) that mass content is 60% is distributed in tetrahydrofuran 250g, Cyclopentadiene 40g (0.6mol) is added, maintaining reaction temperature stirs 1h at 30 DEG C, and dimethyl is added after boiling off tetrahydrofuran in decompression Sulfoxide 50g obtains the dimethylsulfide complex solution of cyclopentadienyl sodium；N-hexane 150g is added into solution again, it is cooling To 0 DEG C, isopropyl bromide 147g (1.2mol) is instilled in 50min, the temperature of charging present invention liquid is no more than 5 DEG C, when adding Temperature be no more than 10 DEG C, hydrochloric acid solution 60g (0.6mol) and n-hexane 150g is slowly added dropwise, is stirred to react in 10 DEG C, standing Separation organic layer obtains the solution of the isopropylcyclopentadiene containing 1-, and GC analyzes the mass ratio 1- isopropyl basic rings of product and isomers Pentadiene:5- isopropylcyclopentadienes:Isopropylcyclopentadiene=30.5 2-:49.1:20.4, Ru will be added in this solution (Ac)3The mass ratio for carrying out isomerization reaction 6h, GC analysis product and isomers after-ZSM-5 4g in 20.0 DEG C of stirrings becomes 1- isopropylcyclopentadienes:5- isopropylcyclopentadienes:Isopropylcyclopentadiene=96.3 2-:2.4:1.3 (yield is low) filter Reaction solution obtains 1- isopropylcyclopentadiene 20g, yield 31% after concentration.
Embodiment 5
Under nitrogen protection, the sodium hydride 72g (1.8mol) that mass content is 60% is distributed in tetrahydrofuran 250g, Cyclopentadiene 40g (0.6mol) is added, maintaining reaction temperature stirs 1h at 30 DEG C, and dimethyl is added after boiling off tetrahydrofuran in decompression Sulfoxide 50g obtains the dimethylsulfide complex solution of cyclopentadienyl sodium；N-hexane 150g is added into solution again, it is cooling To 0 DEG C, isopropyl bromide 147g (1.2mol) is instilled in 50min, the temperature of charging present invention liquid is no more than 5 DEG C, when adding Temperature be no more than 10 DEG C, hydrochloric acid solution 180g (1.8mol) and n-hexane 150g is slowly added dropwise, is stirred to react in 10 DEG C, standing Separation organic layer obtains the solution of the isopropylcyclopentadiene containing 1-, and GC analyzes the mass ratio 1- isopropyl basic rings of product and isomers Pentadiene:5- isopropylcyclopentadienes:Isopropylcyclopentadiene=39.8 2-:32.3:27.9, Ru will be added in this solution (Ac)3The mass ratio for carrying out isomerization reaction 6h, GC analysis product and isomers after-ZSM-5 4g in 20.0 DEG C of stirrings becomes 1- isopropylcyclopentadienes:5- isopropylcyclopentadienes:Isopropylcyclopentadiene=97.4 2-:0.8:1.8 (yield is low) filter Reaction solution obtains 1- isopropylcyclopentadiene 53.7g, yield 83% after concentration.
Embodiment 6
Under nitrogen protection, hydrofining 24g (0.6mol) is distributed in tetrahydrofuran 250g, cyclopentadiene 40g is added (0.6mol), maintaining reaction temperature stir 1h at 30 DEG C, and decompression is added dimethyl sulfoxide (DMSO) 50g after boiling off tetrahydrofuran, obtains ring The dimethylsulfide complex solution of pentadienyl sodium；N-hexane 150g is added into solution again, 0 DEG C is cooled to, in 50min Isopropyl bromide 147g (1.2mol) is instilled, the temperature of charging present invention liquid is no more than 5 DEG C, and temperature when adding is no more than 10 DEG C, hydrochloric acid solution 60g (0.6mol) and n-hexane 150g is slowly added dropwise, is stirred to react in 10 DEG C, standing separation organic layer obtains The solution of the isopropylcyclopentadiene containing 1-, GC analyze the mass ratio 1- isopropylcyclopentadienes of product and isomers:5- isopropyls Butylcyclopentadiene:Isopropylcyclopentadiene=49.6 2-:33.4:17.0, Ru (Ac) will be added in this solution3After-ZSM-5 4g The mass ratio that isomerization reaction 6h, GC analysis product and isomers are carried out in 20.0 DEG C of stirrings becomes 1- isopropyls basic ring penta 2 Alkene:5- isopropylcyclopentadienes:Isopropylcyclopentadiene=97.8 2-:0.9:1.3 (hydrofining price, high incomes) filter Reaction solution obtains 1- isopropylcyclopentadiene 30g, yield 47% after concentration.
Embodiment 7
Under nitrogen protection, hydrofining 72g (1.8mol) is distributed in tetrahydrofuran 250g, cyclopentadiene 40g is added (0.6mol), maintaining reaction temperature stir 1h at 30 DEG C, and decompression is added dimethyl sulfoxide (DMSO) 50g after boiling off tetrahydrofuran, obtains ring The dimethylsulfide complex solution of pentadienyl sodium；N-hexane 150g is added into solution again, 0 DEG C is cooled to, in 50min Isopropyl bromide 147g (1.2mol) is instilled, the temperature of charging present invention liquid is no more than 5 DEG C, and temperature when adding is no more than 10 DEG C, hydrochloric acid solution 180g (1.8mol) and n-hexane 150g is slowly added dropwise, is stirred to react in 10 DEG C, standing separation organic layer obtains The solution of the isopropylcyclopentadiene containing 1-, GC analyze the mass ratio 1- isopropylcyclopentadienes of product and isomers:5- isopropyls Butylcyclopentadiene:Isopropylcyclopentadiene=53.5 2-:21.4:25.1 Ru (Ac) will be added in this solution3After-ZSM-5 4g The mass ratio that isomerization reaction 6h, GC analysis product and isomers are carried out in 20.0 DEG C of stirrings becomes 1- isopropyls basic ring penta 2 Alkene:5- isopropylcyclopentadienes:Isopropylcyclopentadiene=98.7 2-:0.4:0.9 (hydrofining price, high income) filters Reaction solution obtains 1- isopropylcyclopentadiene 62.8g, yield 98% after concentration.
Embodiment 8
Under nitrogen protection, hydrofining 72g (1.8mol) is distributed in tetrahydrofuran 250g, cyclopentadiene 40g is added (0.6mol), maintaining reaction temperature stir 1h at 30 DEG C, and decompression is added dimethyl sulfoxide (DMSO) 50g after boiling off tetrahydrofuran, obtains ring The dimethylsulfide complex solution of pentadienyl sodium；N-hexane 150g is added into solution again, 0 DEG C is cooled to, in 50min Isopropyl bromide 122g (1.0mol) is instilled, the temperature of charging present invention liquid is no more than 5 DEG C, and temperature when adding is no more than 10 DEG C, hydrochloric acid solution 180g (1.8mol) and n-hexane 150g is slowly added dropwise, is stirred to react in 10 DEG C, standing separation organic layer obtains The solution of the isopropylcyclopentadiene containing 1-, GC analyze the mass ratio 1- isopropylcyclopentadienes of product and isomers:5- isopropyls Butylcyclopentadiene:Isopropylcyclopentadiene=53.5 2-:21.4:25.1, Ru (Ac) will be added in this solution3After-ZSM-5 4g The mass ratio that isomerization reaction 6h, GC analysis product and isomers are carried out in 20.0 DEG C of stirrings becomes 1- isopropyls basic ring penta 2 Alkene:5- isopropylcyclopentadienes:Isopropylcyclopentadiene=98.1 2-:1.1:0.8 (yield is low) filters reaction solution, after concentration Obtain 1- isopropylcyclopentadiene 51.2g, yield 79%.
Embodiment 9
Under nitrogen protection, hydrofining 72g (1.8mol) is distributed in tetrahydrofuran 250g, cyclopentadiene 40g is added (0.6mol), maintaining reaction temperature stir 1h at 30 DEG C, and decompression is added dimethyl sulfoxide (DMSO) 50g after boiling off tetrahydrofuran, obtains ring The dimethylsulfide complex solution of pentadienyl sodium；N-hexane 150g is added into solution again, 0 DEG C is cooled to, in 50min Isopropyl bromide 110g (0.9mol) is instilled, the temperature of charging present invention liquid is no more than 5 DEG C, and temperature when adding is no more than 10 DEG C, hydrochloric acid solution 180g (1.8mol) and n-hexane 150g is slowly added dropwise, is stirred to react in 10 DEG C, standing separation organic layer obtains The solution of the isopropylcyclopentadiene containing 1-, GC analyze the mass ratio 1- isopropylcyclopentadienes of product and isomers:5- isopropyls Butylcyclopentadiene:Isopropylcyclopentadiene=53.5 2-:21.4:25.1, Ru (Ac) will be added in this solution3After-ZSM-5 4g The mass ratio that isomerization reaction 6h, GC analysis product and isomers are carried out in 20.0 DEG C of stirrings becomes 1- isopropyls basic ring penta 2 Alkene:5- isopropylcyclopentadienes:Isopropylcyclopentadiene=98.7 2-:0.4:0.9 (yield is low) filters reaction solution, after concentration Obtain 1- isopropylcyclopentadiene 50g, yield 77%.
Embodiment 10
Under nitrogen protection, hydrofining 72g (1.8mol) is distributed in tetrahydrofuran 250g, cyclopentadiene 40g is added (0.6mol), maintaining reaction temperature stir 1h at 30 DEG C, and decompression is added dimethyl sulfoxide (DMSO) 50g after boiling off tetrahydrofuran, obtains ring The dimethylsulfide complex solution of pentadienyl sodium；N-hexane 150g is added into solution again, 0 DEG C is cooled to, in 50min Isopropyl bromide 122g (1.0mol) is instilled, the temperature of charging present invention liquid is no more than 5 DEG C, and temperature when adding is no more than 10 DEG C, hydrochloric acid solution 144g (1.44mol) and n-hexane 150g is slowly added dropwise, is stirred to react in 10 DEG C, standing separation organic layer obtains To the solution of the isopropylcyclopentadiene containing 1-, GC analyzes the mass ratio 1- isopropylcyclopentadienes of product and isomers:5- is different Propyl cyclopentadiene:Isopropylcyclopentadiene=29.3 2-:33.6:37.1, Ru (Ac) will be added in this solution3-ZSM-5 4g The mass ratio for carrying out isomerization reaction 10h, GC analysis product and isomers in 20.0 DEG C of stirrings afterwards becomes 1- isopropyls basic ring penta Diene:5- isopropylcyclopentadienes:Isopropylcyclopentadiene=94.9 2-:3.5:1.6 (yield is low) filter reaction solution, concentration After obtain 1- isopropylcyclopentadiene 42.1g, yield 65%.
Embodiment 11
Under nitrogen protection, hydrofining 72g (1.8mol) is distributed in tetrahydrofuran 250g, cyclopentadiene 40g is added (0.6mol), maintaining reaction temperature stir 1h at 30 DEG C, and decompression is added dimethyl sulfoxide (DMSO) 50g after boiling off tetrahydrofuran, obtains ring The dimethylsulfide complex solution of pentadienyl sodium；N-hexane 150g is added into this solution, 0 DEG C is cooled to, in 50min Isopropyl bromide 122g (1.0mol) is instilled, the temperature of charging present invention liquid is no more than 5 DEG C, and temperature when adding is no more than 10 DEG C, hydrochloric acid solution 216g (2.16mol) and n-hexane 150g is slowly added dropwise, is stirred to react in 10 DEG C, standing separation organic layer obtains To the solution of the isopropylcyclopentadiene containing 1-, GC analyzes the mass ratio 1- isopropylcyclopentadienes of product and isomers:5- is different Propyl cyclopentadiene:Isopropylcyclopentadiene=60.3 2-:27.4:12.3, Ru (Ac) will be added in this solution3-ZSM-5 4g The mass ratio for carrying out isomerization reaction 6h, GC analysis product and isomers in 20.0 DEG C of stirrings afterwards becomes 1- isopropyls basic ring penta 2 Alkene:5- isopropylcyclopentadienes:Isopropylcyclopentadiene=98.9 2-:0.6:0.5 (yield is low) filters reaction solution, after concentration Obtain 1- isopropylcyclopentadiene 61.5g, yield 95%.
Embodiment 12
Under nitrogen protection, hydrofining 72g (1.8mol) is distributed in tetrahydrofuran 250g, cyclopentadiene 40g is added (0.6mol), maintaining reaction temperature stir 1h at 30 DEG C, and decompression is added dimethyl sulfoxide (DMSO) 50g after boiling off tetrahydrofuran, obtains ring The dimethylsulfide complex solution of pentadienyl sodium；N-hexane 150g is added into this solution, 0 DEG C is cooled to, in 50min Isopropyl bromide 122g (1.0mol) is instilled, the temperature of charging present invention liquid is no more than 5 DEG C, and temperature when adding is no more than 10 DEG C, hydrochloric acid solution 216g (2.16mol) and n-hexane 150g is slowly added dropwise, is stirred to react in 10 DEG C, standing separation organic layer obtains To the solution of the isopropylcyclopentadiene containing 1-, GC analyzes the mass ratio 1- isopropylcyclopentadienes of product and isomers:5- is different Propyl cyclopentadiene:Isopropylcyclopentadiene=60.3 2-:27.4:12.3, Ru (Ac) will be added in this solution3- ZSM-5 is ( It is primary through using) isomerization reaction 6h are carried out in 20.0 DEG C of stirrings after 4g, GC analyzes products and the mass ratio of isomers becomes At 1- isopropylcyclopentadienes:5- isopropylcyclopentadienes:Isopropylcyclopentadiene=98.7 2-:0.6:0.7, filter reaction Liquid obtains 1- isopropylcyclopentadiene 59g, yield 91% after concentration.
Embodiment 13
Under nitrogen protection, hydrofining 72g (1.8mol) is distributed in tetrahydrofuran 250g, cyclopentadiene 40g is added (0.6mol), maintaining reaction temperature stir 1h at 30 DEG C, and decompression is added dimethyl sulfoxide (DMSO) 50g after boiling off tetrahydrofuran, obtains ring The dimethylsulfide complex solution of pentadienyl sodium；N-hexane 150g is added into this solution, 0 DEG C is cooled to, in 50min Isopropyl bromide 122g (1.0mol) is instilled, the temperature of charging present invention liquid is no more than 5 DEG C, and temperature when adding is no more than 10 DEG C, hydrochloric acid solution 216g (2.16mol) and n-hexane 150g is slowly added dropwise, is stirred to react in 10 DEG C, standing separation organic layer obtains To the solution of the isopropylcyclopentadiene containing 1-, GC analyzes the mass ratio 1- isopropylcyclopentadienes of product and isomers:5- is different Propyl cyclopentadiene:Isopropylcyclopentadiene=60.3 2-:27.4:12.3, Ru (Ac) will be added in this solution3- ZSM-5 is ( It is secondary through using) isomerization reaction 6h are carried out in 20.0 DEG C of stirrings after 4g, GC analyzes products and the mass ratio of isomers becomes At 1- isopropylcyclopentadienes:5- isopropylcyclopentadienes:Isopropylcyclopentadiene=98.2 2-:1.1:0.7, filter reaction Liquid obtains 1- isopropylcyclopentadiene 56.3g, yield 87% after concentration.
Embodiment 14
Under nitrogen protection, hydrofining 72g (1.8mol) is distributed in tetrahydrofuran 250g, cyclopentadiene 40g is added (0.6mol), maintaining reaction temperature stir 1h at 30 DEG C, and decompression is added dimethyl sulfoxide (DMSO) 50g after boiling off tetrahydrofuran, obtains ring The dimethylsulfide complex solution of pentadienyl sodium；N-hexane 150g is added into this solution, 0 DEG C is cooled to, in 50min Isopropyl bromide 122g (1.0mol) is instilled, the temperature of charging present invention liquid is no more than 5 DEG C, and temperature when adding is no more than 10 DEG C, hydrochloric acid solution 216g (2.16mol) and n-hexane 150g is slowly added dropwise, is stirred to react in 10 DEG C, standing separation organic layer obtains To the solution of the isopropylcyclopentadiene containing 1-, GC analyzes the mass ratio 1- isopropylcyclopentadienes of product and isomers:5- is different Propyl cyclopentadiene:Isopropylcyclopentadiene=60.3 2-:27.4:12.3, Ru (Ac) will be added in this solution3- ZSM-5 is ( Through using three times) isomerization reaction 6h are carried out in 20.0 DEG C of stirrings after 4g, GC analyzes products and the mass ratio of isomers becomes At 1- isopropylcyclopentadienes:5- isopropylcyclopentadienes:Isopropylcyclopentadiene=97.9 2-:0.9:1.2, filter reaction Liquid obtains 1- isopropylcyclopentadiene 55g, yield 85% after concentration.
Embodiment 15
Under nitrogen protection, hydrofining 72g (1.8mol) is distributed in tetrahydrofuran 250g, cyclopentadiene 40g is added (0.6mol), maintaining reaction temperature stir 1h at 30 DEG C, and decompression is added dimethyl sulfoxide (DMSO) 50g after boiling off tetrahydrofuran, obtains ring The dimethylsulfide complex solution of pentadienyl sodium；N-hexane 150g is added into solution again, 0 DEG C is cooled to, in 50min Isopropyl bromide 147g (1.2mol) is instilled, the temperature of charging present invention liquid is no more than 5 DEG C, and temperature when adding is no more than 10 DEG C, hydrochloric acid solution 60g (0.6mol) and n-hexane 150g is slowly added dropwise, is stirred to react in 10 DEG C, standing separation organic layer obtains The solution of the isopropylcyclopentadiene containing 1-, GC analyze the mass ratio 1- isopropylcyclopentadienes of product and isomers:5- isopropyls Butylcyclopentadiene:Isopropylcyclopentadiene=53.5 2-:21.4:25.1, RuCl will be added in this solution3.3H2In 20.0 after O4g DEG C stirring carries out isomerization reaction 6h, and the mass ratio of GC analysis products and isomers becomes 1- isopropylcyclopentadienes:5- is different Propyl cyclopentadiene:Isopropylcyclopentadiene=93.2 2-:3.8:3.0, reaction solution is filtered, 1- isopropyls basic ring penta is obtained after concentration Diene 56.5g, yield 88%.
Embodiment 16
In reaction bulb, 1- isopropylcyclopentadienes 54g (0.5mol) is added in n-hexane 150mL, keeps solution Dichloroacetyl chloride 80g (0.55mol) is added at 0 DEG C in temperature, keeps solution temperature at 0 DEG C, and triethylamine 66.58g is added dropwise in 2h (0.658mol), it is 5~6 that glacial acetic acid is added after dripping and adjusts the pH of reaction solution, separates organic layer, obtains isopropyl containing 1- Cyclopenta 4, the hexane solution of 4- dichloro ring fourth 5- ketone boil off vacuum distillation after solvent and obtain 1- isopropylcyclopentadienes And 4,4- dichloro ring fourth 5- ketone 89g (0.410mol), yield 82%, the mass ratio that GC analyzes isomers are 1- isopropyl basic rings Pentadiene and 4,4- dichloro ring fourth 5- ketone:5- isopropylcyclopentadienes and 4,4- dichloro ring fourth 5- ketone:2- isopropylcyclopentadienes And ketone=99.3 4,4- dichloro ring fourth 5-:0.2:0.5.
Embodiment 17
In reaction bulb, 1- isopropylcyclopentadienes 54g (0.5mol) is added in n-hexane 150mL, keeps solution Dichloroacetyl chloride 84g (0.575mol) is added at 0 DEG C in temperature, keeps solution temperature at 0 DEG C, triethylamine is added dropwise in 2h 66.58g (0.658mol), it is 5~6 that glacial acetic acid is added after dripping and adjusts the pH of reaction solution, separates organic layer, obtains containing 1- The hexane solution of isopropylcyclopentadiene and 4,4- dichloro ring fourth 5- ketone, after boiling off solvent vacuum distillation obtain 1- isopropyl basic rings Pentadiene and 4,4- dichloro ring fourth 5- ketone 105g (0.480mol), yield 98%, the ratio that GC analyzes isomers are 1- isopropyls Butylcyclopentadiene and 4,4- dichloro ring fourth 5- ketone:5- isopropylcyclopentadienes and 4,4- dichloro ring fourth 5- ketone:2- isopropyls basic ring penta Diene and ketone=99.8 4,4- dichloro ring fourth 5-:0:0.2.
Embodiment 18
In reaction bulb, 1- isopropylcyclopentadienes 54g (0.5mol) is added in n-hexane 150mL, keeps solution Dichloroacetyl chloride 95g (0.65mol) is added at 0 DEG C in temperature, keeps solution temperature at 0 DEG C, and triethylamine 66.58g is added dropwise in 2h (0.658mol), it is 5~6 that glacial acetic acid is added after dripping and adjusts the pH of reaction solution, separates organic layer, obtains isopropyl containing 1- Cyclopenta 4, the hexane solution of 4- dichloro ring fourth 5- ketone boil off vacuum distillation after solvent and obtain 1- isopropylcyclopentadienes And 4,4- dichloro ring fourth 5- ketone 104g (0.475mol), yield 97%, the mass ratio that GC analyzes isomers are 1- isopropyls Cyclopenta 4,4- dichloro ring fourth 5- ketone:5- isopropylcyclopentadienes and 4,4- dichloro ring fourth 5- ketone:2- isopropyls basic ring penta 2 Alkene and ketone=99.6 4,4- dichloro ring fourth 5-:0.1:0.3.
Embodiment 19
By 1- isopropylcyclopentadienes, simultaneously 4,4- dichloro ring fourth 5- ketone 218g (1.0mol) are dissolved in tert-butyl alcohol 1000g, water The in the mixed solvent of 280g and acetic acid 240g (4.0mol), are heated to reflux, and in 2.5h, triethylamine 606g is added dropwise under return stirring (6.0mol), carry out decomposition reaction, be added dropwise postcooling arrive room temperature, addition water 1500g and concentrated hydrochloric acid 120g, add just oneself Alkane 1000mL stirs 10min, stands 10min, detaches organic layer, and decompression boils off solvent, obtains Hinokitiol crude product 142g；By Chinese juniper Another name for crude product is evaporated under reduced pressure, and after 45~90 DEG C/1mm Hg distillate front-end volatiles, collects the main distillate fraction of about 95 DEG C/1mm Hg, Obtain Hinokitiol sterling 127g；This fraction is dissolved in n-hexane 500mL at 40 DEG C, is cooled down with the rate of temperature fall of 1~2 DEG C/min To 0 DEG C, crystallization is precipitated, filters, is washed with the n-hexane for being cooled to 0 DEG C, it is dry, Hinokitiol crystallized product 113g is obtained, yield is 69%.
Embodiment 20
By 1- isopropylcyclopentadienes, simultaneously 4,4- dichloro ring fourth 5- ketone 218g (1.0mol) are dissolved in tert-butyl alcohol 1000g, water The in the mixed solvent of 280g and acetic acid 300g (5.0mol), are heated to reflux, and in 2.5h, triethylamine 606g is added dropwise under return stirring (6.0mol), carry out decomposition reaction, be added dropwise postcooling arrive room temperature, addition water 1500g and concentrated hydrochloric acid 120g, add just oneself Alkane 1000mL stirs 10min, stands 10min, detaches organic layer, and decompression boils off solvent, obtains Hinokitiol crude product 155g；By Chinese juniper Another name for crude product is evaporated under reduced pressure, and after 45~90 DEG C/1mm Hg distillate front-end volatiles, collects the main distillate fraction of about 95 DEG C/1mm Hg, Obtain Hinokitiol sterling 147g；This fraction is dissolved in n-hexane 500mL at 40 DEG C, is cooled down with the rate of temperature fall of 1~2 DEG C/min To 0 DEG C, crystallization is precipitated, filters, is washed with the n-hexane for being cooled to 0 DEG C, it is dry, Hinokitiol crystallized product 135g is obtained, yield is 82%.
Embodiment 21
By 1- isopropylcyclopentadienes, simultaneously 4,4- dichloro ring fourth 5- ketone 218g (1.0mol) are dissolved in tert-butyl alcohol 1000g, water The in the mixed solvent of 280g and acetic acid 360g (6.0mol), are heated to reflux, and in 2.5h, triethylamine 606g is added dropwise under return stirring (6.0mol), carry out decomposition reaction, be added dropwise postcooling arrive room temperature, addition water 1500g and concentrated hydrochloric acid 120g, add just oneself Alkane 1000mL stirs 10min, stands 10min, detaches organic layer, and decompression boils off solvent, obtains Hinokitiol crude product 161g；By Chinese juniper Another name for crude product is evaporated under reduced pressure, and after 45~90 DEG C/1mm Hg distillate front-end volatiles, collects the main distillate fraction of about 95 DEG C/1mm Hg, Obtain Hinokitiol sterling 145g；This fraction is dissolved in n-hexane 500mL at 40 DEG C, is cooled down with the rate of temperature fall of 1~2 DEG C/min To 0 DEG C, crystallization is precipitated, filters, is washed with the n-hexane for being cooled to 0 DEG C, it is dry, Hinokitiol crystallized product 133g is obtained, yield is 81%.
Embodiment 22
By 1- isopropylcyclopentadienes, simultaneously 4,4- dichloro ring fourth 5- ketone 218g (1.0mol) are dissolved in tert-butyl alcohol 1000g, water The in the mixed solvent of 280g and acetic acid 300g (5.0mol), are heated to reflux, and in 2.5h, triethylamine 606g is added dropwise under return stirring (6.0mol), carry out decomposition reaction, be added dropwise postcooling arrive room temperature, addition water 1500g and concentrated hydrochloric acid 120g, add just oneself Alkane 1000mL stirs 10min, stands 10min, detaches organic layer, and decompression boils off solvent, obtains Hinokitiol crude product 155g；By Chinese juniper Another name for crude product is evaporated under reduced pressure, and after 45~90 DEG C/1mm Hg distillate front-end volatiles, collects the main distillate fraction of about 95 DEG C/1mm Hg, Obtain Hinokitiol sterling 147g；This fraction is dissolved in acetone 500mL at 40 DEG C, is cooled to the rate of temperature fall of 1~2 DEG C/min 0 DEG C, crystallization is precipitated, filters, is washed with the n-hexane for being cooled to 0 DEG C, it is dry, Hinokitiol crystallized product 80g is obtained, yield is 49%.
Embodiment 23
By 1- isopropylcyclopentadienes, simultaneously 4,4- dichloro ring fourth 5- ketone 218g (1.0mol) are dissolved in tert-butyl alcohol 1000g, water The in the mixed solvent of 280g and acetic acid 300g (5.0mol), are heated to reflux, and in 2.5h, triethylamine 606g is added dropwise under return stirring (6.0mol), carry out decomposition reaction, be added dropwise postcooling arrive room temperature, addition water 1500g and concentrated hydrochloric acid 120g, add just oneself Alkane 1000mL stirs 10min, stands 10min, detaches organic layer, and decompression boils off solvent, obtains Hinokitiol crude product 155g；By Chinese juniper Another name for crude product is evaporated under reduced pressure, and after 45~90 DEG C/1mm Hg distillate front-end volatiles, collects the main distillate fraction of about 95 DEG C/1mm Hg, Obtain Hinokitiol sterling 147g；This fraction is dissolved in isopropanol 500mL at 40 DEG C, is cooled down with the rate of temperature fall of 1~2 DEG C/min To 0 DEG C, crystallization is precipitated, filters, is washed with the n-hexane for being cooled to 0 DEG C, it is dry, Hinokitiol crystallized product 103g is obtained, yield is 63%.
Embodiment 24
By 1- isopropylcyclopentadienes, simultaneously 4,4- dichloro ring fourth 5- ketone 218g (1.0mol) are dissolved in tert-butyl alcohol 1000g, water The in the mixed solvent of 280g and acetic acid 300g (5.0mol), are heated to reflux, and in 2.5h, triethylamine 606g is added dropwise under return stirring (6.0mol), carry out decomposition reaction, be added dropwise postcooling arrive room temperature, addition water 1500g and concentrated hydrochloric acid 120g, add just oneself Alkane 1000mL stirs 10min, stands 10min, detaches organic layer, and decompression boils off solvent, obtains Hinokitiol crude product 155g；By Chinese juniper Another name for crude product is evaporated under reduced pressure, and after 45~90 DEG C/1mm Hg distillate front-end volatiles, collects the main distillate fraction of about 95 DEG C/1mm Hg, Obtain Hinokitiol sterling 147g；It is 1 that this fraction, which is dissolved in volume ratio, at 40 DEG C:1 acetone/hexamethylene mixed liquor 500mL, with The rate of temperature fall of 1~2 DEG C/min is cooled to 0 DEG C, and crystallization is precipitated, and filters, is washed with the n-hexane for being cooled to 0 DEG C, dry, obtains Chinese juniper Another name for crystallized product 125g, yield 76%.
Have been shown and described above the basic principle of the present invention, main feature and advantage, do not depart from spirit of that invention and Under the premise of range, the present invention also has various changes and modifications, these changes and improvements both fall within claimed invention Range.

Claims (8)

1. a kind of preparation method of high-purity Hinokitiol, it is characterised in that the specific steps are：
Step A, it is obtained by the reaction with isopropyl bromide containing there are many isopropyl basic rings of isomers after the activated reagent activation of cyclopentadiene Pentadiene, then carry out isomerization reaction under the action of isomers reforming catalyst and obtain 1- isopropylcyclopentadienes, wherein living Change reagent is metallic sodium, lithium metal, sodium hydride or hydrofining, and isomers reforming catalyst is RuCl3·3H2O、Ru(acac)3、 Ru(Ac)3- ZSM-5 or Ru (NO) (NO3)3；
Step B, 1- isopropylcyclopentadienes react to obtain 1- isopropylcyclopentadienes and 4,4- dichloro rings with dichloro cyclic ketones Fourth 5- ketone；
Step C, 1- isopropylcyclopentadienes and 4,4- dichloro ring fourth 5- ketone are heated to reflux generation ring expansion with triethylamine and obtain Target product Hinokitiol.
2. the preparation method of high-purity Hinokitiol according to claim 1, it is characterised in that the detailed process of step A is： Activating reagent is distributed in tetrahydrofuran under inert gas protection, cyclopentadiene is added, 1h is stirred to react in 30 DEG C, is depressurized Dimethyl sulfoxide (DMSO) is added after boiling off tetrahydrofuran, the dimethylsulfide complex solution of the cyclopentadiene after being activated；Again to N-hexane is added in solution, is cooled to 0 DEG C of dropwise addition isopropyl bromide, the temperature of charging present invention liquid is no more than 5 DEG C, when adding Temperature is no more than 10 DEG C, then hydrochloric acid solution and n-hexane is added dropwise, and is stirred to react in 10 DEG C, after reaction standing separation organic layer Obtain the solution containing isopropylcyclopentadiene；Isomers reforming catalyst is added in the solution containing isopropylcyclopentadiene, And isomerization reaction is carried out in 20 DEG C of stirrings, filtering reacting liquid obtains 1- isopropylcyclopentadienes after concentration, isomers conversion is urged Agent repetitive cycling uses.
3. the preparation method of high-purity Hinokitiol according to claim 2, it is characterised in that：Ring penta 2 described in step A The molar ratio of alkene and activating reagent is 1:1~3；The mass ratio that feeds intake of cyclopentadiene and dimethyl sulfoxide (DMSO) is 1:1.25；Ring The molar ratio of pentadiene and isopropyl bromide is 1:1.5~2；The molar ratio of cyclopentadiene and HCl are 1:0.8~1.2.
4. the preparation method of high-purity Hinokitiol according to claim 1, it is characterised in that the detailed process of step B is： 1- isopropylcyclopentadienes are added in n-hexane, keep solution temperature at 0 DEG C, dichloroacetyl chloride is added and keeps solution temperature At 0 DEG C, then triethylamine is added dropwise, glacial acetic acid is added after being added dropwise, the pH for adjusting reaction solution is 5~6, and steaming is depressurized after boiling off solvent It evaporates to obtain 1- isopropylcyclopentadienes and 4,4- dichloro ring fourth 5- ketone.
5. the preparation method of high-purity Hinokitiol according to claim 4, it is characterised in that：Isopropyl described in step B The molar ratio of cyclopentadiene and dichloroacetyl chloride is 1:1~1.3.
6. the preparation method of high-purity Hinokitiol according to claim 1, it is characterised in that the detailed process of step C is： 1- isopropylcyclopentadienes and 4,4- dichloro ring fourth 5- ketone are dissolved in the in the mixed solvent of the tert-butyl alcohol, water and acetic acid, are heated to reflux Stirring is lower to be added dropwise triethylamine progress back flow reaction, adds postcooling to room temperature, adds water, concentrated hydrochloric acid and n-hexane, after stirring Organic layer decompression is boiled off solvent and obtains Hinokitiol crude product, Hinokitiol crude product is evaporated under reduced pressure, 45~90 by stratification DEG C/1mm Hg distillate and collect the main distillate fraction of 95 DEG C/1mm Hg after front-end volatiles and obtain Hinokitiol, it is in 40 DEG C that Hinokitiol main distillate fraction is molten In recrystallization solution, be cooled to 0 DEG C with the rate of temperature fall of 1~2 DEG C/min, crystallization be precipitated, filter, be cooled to 0 DEG C third Ketone washs, dry, obtains Hinokitiol crystallized product.
7. the preparation method of high-purity Hinokitiol according to claim 6, it is characterised in that：1- isopropyls described in step C The molar ratio of butylcyclopentadiene and 4,4- dichloro ring fourth 5- ketone and acetic acid is 1:4~6；1- isopropylcyclopentadienes and 4,4- The molar ratio of dichloro ring fourth 5- ketone and triethylamine is 1:6.
8. the preparation method of high-purity Hinokitiol according to claim 6, it is characterised in that：The recrystallization solution is third Ketone, isopropanol, hexamethylene, acetone and the mixed liquor or acetone of isopropanol and the mixed liquor of hexamethylene, acetone and isopropanol mix Close the volume ratio 1 of acetone and isopropanol in solution:1, the volume ratio of acetone and hexamethylene in the mixed solution of acetone and hexamethylene 1:1。
CN201810032873.9A 2018-01-13 2018-01-13 A kind of preparation method of high-purity Hinokitiol Pending CN108314615A (en)

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CN1177789C (en) * 1998-03-30 2004-12-01 旭化成株式会社 Process for producing hinokitiol
CN101602656A (en) * 2009-07-20 2009-12-16 辽宁科技大学 A kind of synthetic method of chamaecypariol

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JPS5133901B1 (en) * 1970-12-29 1976-09-22
CN1177789C (en) * 1998-03-30 2004-12-01 旭化成株式会社 Process for producing hinokitiol
JP2004285028A (en) * 2003-03-25 2004-10-14 Takasago Internatl Corp Method for producing 1-isopropylcyclopentadiene and hinokitiol
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Application publication date: 20180724