CN104447826A - 1,2-dihydrocyclobuteno[alpha]naphthyridine-4-boronic acid compound and preparation method thereof - Google Patents
1,2-dihydrocyclobuteno[alpha]naphthyridine-4-boronic acid compound and preparation method thereof Download PDFInfo
- Publication number
- CN104447826A CN104447826A CN201410603576.7A CN201410603576A CN104447826A CN 104447826 A CN104447826 A CN 104447826A CN 201410603576 A CN201410603576 A CN 201410603576A CN 104447826 A CN104447826 A CN 104447826A
- Authority
- CN
- China
- Prior art keywords
- naphthalene
- cyclobutene
- dihydro
- reaction
- bromo
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 0 C*c1cc(CC2)c2c2c1cccc2 Chemical compound C*c1cc(CC2)c2c2c1cccc2 0.000 description 3
- YINJJVIRAIWXLB-UHFFFAOYSA-N Brc1cc(CC2)c2c2c1cccc2 Chemical compound Brc1cc(CC2)c2c2c1cccc2 YINJJVIRAIWXLB-UHFFFAOYSA-N 0.000 description 1
- OIGRSMRBRSPKDY-UHFFFAOYSA-N Cc1cc(CC2)c2c2c1cccc2 Chemical compound Cc1cc(CC2)c2c2c1cccc2 OIGRSMRBRSPKDY-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic System
- C07F5/02—Boron compounds
- C07F5/025—Boronic and borinic acid compounds
Abstract
The invention discloses a novel method for synthesizing 1,2-dihydrocyclobuteno[alpha]naphthalene-4-boronic acid. The method comprises the following steps: (1) preparing 4-bromo-1,2-dihydrocyclobuteno[alpha]naphthalene from 1,2-dihydrocyclobuteno[alpha]naphthalene as a raw material; (2) in the presence of nitrogen, dropwise adding a 4-bromo-1,2-dihydrocyclobuteno[alpha]naphthalenetetrahydrofuran solution into a reactor filled with tetrahydrofuran, magnesium chips and iodine particles and after the dropwise addition is completed, reacting at 50-70 DEG C to obtain a reaction liquid; (3) placing the reaction liquid into a low-temperature reactor, at -100 to -60 DEG C, dropwise adding trimethyl borate into the reaction liquid, reacting, heating to room temperature and further reacting to obtain a reaction liquid; and (4) injecting the reaction liquid into cold diluted dhydrochloric acid, stirring, extracting with diethyl ether, respectively washing with deionized water and a saturated sodium chloride aqueous solution once, separating an organic phase, drying and removing the solvent by virtue of rotary evaporation to obtain a solid substance and recrystallizing the solid substance to obtain 1,2-dihydrocyclobuteno[alpha]naphthalene-4-boronic acid. By adopting independently researched and synthesized 4-bromo-1,2-dihydrocyclobuteno[alpha]naphthalene as the raw material and two-step reaction, 1,2-dihydrocyclobuteno[alpha]naphthalene-4-boronic acid is synthesized and the method has the advantages of stable process, high yield and low cost.
Description
Technical field
The invention belongs to organic chemical synthesis field, be specifically related to the synthetic method of 1,2-dihydro cyclobutene also [α] naphthalene-4-boronic acid compounds.
Background technology
1,2-dihydro cyclobutene also [α] naphthalene-4-boronic acid compounds has broad application prospects, due to the singularity of organic boron acid, at biomedical aspect, not only can be used as the treatment of enzyme inhibitors for the disease such as tumour, infected by microbes, also can be used as fluorescent probe, for identifying the materials such as hydroperoxide kind, carbohydrate, cupric ion, fluorion and catecholamines.In addition, 1,2-dihydro cyclobutene is [α] naphthalene-4-boric acid or important organic intermediate also, very important effect is had in organic synthesis, with 1,2-dihydro cyclobutene also [α] naphthalene-4-boric acid is the catalyst series of base material, and compared with other class catalyzer, safe green, recovery and utilization are also easy is more easy to get.
But in the synthesis of 1,2-dihydro cyclobutene also [α] naphthalene-4-boric acid, the more difficult acquisition of raw material on the one hand, on the other hand, due to the singularity of product structure, synthesis condition is comparatively harsh, the synthetic schemes do not had always.
Summary of the invention
For current 1, the disappearance of 2-dihydro cyclobutene also [α] naphthalene-4-boronic acid compounds synthetic method, the 4-bromo-1 that the present invention synthesizes with independent research, 2-dihydro cyclobutene is [α] naphthalene also, pass through two-step reaction, successfully synthesize 1,2-dihydro cyclobutene also [α] naphthalene-4-boronic acid compounds.
The technical scheme that the present invention prepares 1,2-dihydro cyclobutene also [α] naphthalene-4-boronic acid compounds is:
Wherein the preparation method of compound 1,2-dihydro cyclobutene also [α] naphthalene-4-boronic acid compounds, comprises the steps:
Step one, with 1,2-dihydro cyclobutene also [α] naphthalene is that 4-bromo-1 prepared by raw material, 2-dihydro cyclobutene is [α] naphthalene also, then by obtained 4-bromo-1.2-dihydro cyclobutene also [α] naphthalene be dissolved in dry tetrahydrofuran, obtain bromo-1, the 2-dihydro cyclobutene of 4-also [α] naphthalene solution;
Step 2, under pure nitrogen gas atmosphere protection, dry tetrahydrofuran is added in the reactor filling magnesium chips and initiator iodine grain, then the 4-bromo-1.2-dihydro cyclobutene at room temperature step one obtained while stirring reaction is [α] naphthalene solution instillation reactor also, within 2 ~ 3 hours, drip off, be warming up to 50 ~ 70 DEG C after dripping and continue stirring reaction 1 ~ 3 hour;
Step 3, reaction solution step 2 obtained are transferred in low-temp reaction device, at-100 ~-60 DEG C, while stirring reaction, trimethyl borate is slowly at the uniform velocity added dropwise to reaction solution, within 2 ~ 3 hours, drip off, at-100 ~-60 DEG C, stirring reaction is continued after 1 ~ 3 hour after dripping off, slowly get back to room temperature, and at room temperature stirring reaction 12-36 hour;
Step 4, a certain amount of dilute hydrochloric acid is chilled to 0 ~ 10 DEG C in advance in refrigerator after, reaction solution step 3 obtained slowly injects this cold dilute hydrochloric acid, slowly stirs, add rear acceleration stir, and continue 20 ~ 50 minutes;
Step 5, reaction solution twice by extracted with diethyl ether step 4, merged the organic phase of twice extraction, wash one time respectively, separate organic phase with organic phase equal-volume deionized water and saturated sodium-chloride water solution, with anhydrous sodium sulfate drying 4 ~ 8 hours;
Step 6, material after drying revolved and steams except desolventizing, obtain solid matter, use deionized water/methanol mixed solvent by solid matter recrystallization 2 times, obtain compound 1,2-dihydro cyclobutene also [α] naphthalene-4-boric acid.
Preferably, 4-bromo-1 in described step one, the preparation method of 2-dihydro cyclobutene also [α] naphthalene is: be 1 of 1:6 ~ 10 by weight ratio, 2-dihydro cyclobutene also [α] naphthalene and glacial acetic acid adds in low-temp reaction device, add methyl alcohol simultaneously, wherein the volume ratio of methyl alcohol and glacial acetic acid is 1:8 ~ 12, stirs, after 1 ~ 3 hour, reaction solution is cooled to-10 ~ 0 DEG C; In addition be bromine and the glacial acetic acid mixed dissolution of 1:4 ~ 7 by mol ratio, obtain bromine solution, at-10 ~ 0 DEG C, reaction solution is added dropwise to by bromine solution uniform speed slow while stirring reaction liquid, dripped off in 2 ~ 5 hours, drip off follow-up continuation of insurance temperature 1 ~ 3 hour, obtain reddish-brown reaction solution; Put into low-temp. refrigerator by after reddish-brown reaction solution lucifuge, react after 48 ~ 72 hours at-30 ~-15 DEG C, reaction solution is taken out from low-temp. refrigerator under being placed in room temperature, make reacting liquid temperature reach room temperature; The reaction solution reaching room temperature is added the dichloromethane extraction 2 times of 1 ~ 3 times of reaction solution volume, separate organic phase; In addition be add in organic phase after the Sodium Metabisulfite of 1:15 ~ 25 and deionized water wiring solution-forming to stir 5 ~ 10 minutes by weight ratio, stratification, then uses and washes one time with the isopyknic deionization of organic phase, organic phase separated, dry 4 ~ 8 hours, after concentrated, obtain sticky solid; Use volume ratio to be the sherwood oil of 5 ~ 10:1 and ethyl acetate mixed solvent by sticky solid recrystallization 2 times, obtain bromo-1, the 2-dihydro cyclobutene of faint yellow compound 4-also [α] naphthalene.
Preferably, in described step one and step 2, dry tetrahydrofuran is the dry tetrahydrofuran newly steamed, its drying means is: the potassium hydroxide solid adding mass ratio about 5% after being broken a seal by AR level tetrahydrofuran (THF), seal after suitable concussion and keep in Dark Place, after predrying 24 hours, clear liquid is moved into round-bottomed flask, press-in sodium silk, add the benzophenone that mass ratio is 2 ~ 5 ‰, reflux to liquid steams after becoming mazarine, obtains dry tetrahydrofuran.
Preferably, in described step one, the weight ratio of 4-bromo-1.2-dihydro cyclobutene also [α] naphthalene and dry tetrahydrofuran is 1:6 ~ 10.
Preferably, in described step 2, in magnesium chips and step one, the mol ratio of bromo-1, the 2-dihydro cyclobutene of 4-also [α] naphthalene is 1 ~ 1.1:1, and the consumption of initiator iodine grain is 0.01 ~ 0.02g, and the volume adding dry tetrahydrofuran accounts for 1/50 of reactor capacity.
Preferably, the mol ratio of described step 3 mesoboric acid trimethyl and bromo-1, the 2-dihydro cyclobutene of 4-also [α] naphthalene is 1 ~ 1.1:1.
Preferably, the concentration of dilute hydrochloric acid described in described step 4 is 0.3 ~ 0.5mol/L, and consumption is 2 ~ 3 times of the reaction solution volume that step 3 obtains, and the speed of described slow stirring is 100 revs/min, accelerates the speed 1000 revs/min stirred.
Preferably, in described step 5, the volume of ether is 1/2 of reaction solution volume.
Preferably, in described step 6, the volume ratio of deionized water/methyl alcohol is 5 ~ 10:1, and the color of the solid matter obtained is grey, and the color of 1, the 2-dihydro cyclobutene obtained also [α] naphthalene-4-boronic acid compounds is off-white color.
It should be noted that:
The tetrahydrofuran (THF) used in the present invention is the dry tetrahydrofuran newly steamed; mainly because the reaction of step 2 is grignard reaction; grignard reaction requires to react under anhydrous and oxygen-free condition; moisture has crucial impact to grignard reaction; if there is moisture to exist; reaction can not cause, and therefore need to carry out drying treatment to tetrahydrofuran (THF) and logical nitrogen excluding air is protected reaction.
In the present invention, temperature causes extremely important for grignard reaction, temperature of reaction preferably 50 ~ 70 DEG C, and in this temperature range, reaction can high efficiencyly cause, if temperature exceedes this scope, then linked reaction easily occurs and generates by-product; Temperature lower than this scope, then the reaction times elongated and reaction not thorough.
Step 3 of the present invention uses low-temp reaction device, and reacts at-100 ~-60 DEG C, and its major cause is that the activity of this reaction is higher, and low temperature can suppress the generation of side reaction.
The object of dilute hydrochloric acid is used to be to remove unreacted magnesium in reaction in step 4 of the present invention, the existence of magnesium will affect the purity of reaction product, the object first slowly stirring then rapid stirring is in the process that rapid stirring can make acidification reaction more abundant, and what unreacted magnesium was removed is more thorough.The concentration of dilute hydrochloric acid preferably 0.3 ~ 0.5mol/L is because acidifying is more thorough at this concentration, may to react the acidolysis of product if concentration of hydrochloric acid exceedes this scope, if acidifying may be caused insufficient lower than this scope, not thorough to the removal of magnesium.
The object that the present invention adds organic solvent ether in step 5 is to out be extracted from reaction solution by the organism be obtained by reacting, and the object of twice extraction is to all be extracted by organism as far as possible.The object using deionized water and saturated sodium-chloride water solution to wash organic phase removes water-soluble impurity in organic phase, is finally the moisture that dry above-mentioned deionized water and saturated sodium-chloride water solution are left over by the object of anhydrous sodium sulphate.
The object using deionized water/methanol mixed solvent to carry out recrystallization to solid in the present invention in step 6 is in order to purified reaction product, makes the purity of reaction product higher.
The invention has the beneficial effects as follows: bromo-1, the 2-dihydro cyclobutene of 4-also [α] naphthalene that this programme synthesizes with independent research, pass through two-step reaction, successfully synthesize 1,2-dihydro cyclobutene also [α] naphthalene-4-boric acid, technique is relatively stable, productive rate is higher, and cost is relative moderate also.
Accompanying drawing explanation
Fig. 1 is the chemical equation of technical solution of the present invention.
Embodiment:
Below in conjunction with below in conjunction with the drawings and specific embodiments, the present invention is described in further detail, can implement according to this with reference to specification sheets word to make those skilled in the art.
Embodiment 1:
By 1,2-dihydro cyclobutene also [α] naphthalene 200g, 90% glacial acetic acid 1500mL and methyl alcohol 150mL add in 3000mL low-temp reaction device, stir, after 2 hours, reaction solution be cooled to-5 DEG C; Bromine 200g is dissolved in 90% glacial acetic acid of 500ml, obtains bromine solution, at-5 DEG C, be added dropwise to reaction solution by bromine solution uniform speed slow while stirring reaction liquid, dripped off in 4 hours, drip off follow-up continuation of insurance temperature 1 hour, obtain reddish-brown reaction solution; The reddish-brown reaction solution obtained is transferred to 3000mL brown bottle, put into low-temp. refrigerator, react at-20 DEG C after 72 hours, brown bottle is taken out from low-temp. refrigerator under being placed in room temperature, make reacting liquid temperature reach room temperature, now reaction solution is yellow liquid, is again transferred in 5000mL reaction flask by the yellow reaction liquid obtained, add 2500mL dichloromethane extraction 2 times, separate organic phase; In addition 100g Sodium Metabisulfite is dissolved in wiring solution-forming in 2000ml deionized water, Sodium Metabisulfite solution is added in organic phase and stir 5 minutes, stratification, then use 2000mL deionization to wash one time, organic phase is separated, dry 5 hours, clear yellow viscous solid is obtained after organic phase is concentrated, the petrol ether/ethyl acetate mixed solvent recrystallization that use volume ratio is 5:1 2 times, obtains bromo-1, the 2-dihydro cyclobutene of faint yellow compound 4-also [α] naphthalene.
The potassium hydroxide solid adding mass ratio about 5% after being broken a seal by the AR level tetrahydrofuran (THF) newly bought carries out predrying, seal after suitable concussion and keep in Dark Place, after predrying 24 hours, solid settlement is in bottom, clear liquid is moved into round-bottomed flask, and press-in sodium silk, adds the benzophenone that mass ratio is 5 ‰, reflux to liquid steams after becoming mazarine, obtains dry tetrahydrofuran.
By obtained bromo-1, the 2-dihydro cyclobutene of 4-also [α] naphthalene 150g be dissolved in 1500mL brand-new dry tetrahydrofuran, obtain bromo-1, the 2-dihydro cyclobutene of 4-also [α] naphthalene solution;
Build 3000mL grignard reaction device, under pure nitrogen gas atmosphere protection, 60mL brand-new dry tetrahydrofuran is added in the reactor filling 16.2g magnesium chips and 0.01g initiator iodine grain, then at room temperature while stirring reaction by bromo-for 4-1.2-dihydro cyclobutene also [α] naphthalene solution instillation reactor, within 3 hours, drip off, be warming up to 60 DEG C after dripping and continue stirring reaction 1 hour; The reaction solution obtained is transferred in low-temp reaction device, at-80 DEG C, while stirring reaction, 70.2g trimethyl borate is slowly at the uniform velocity added dropwise to reaction solution, within 2 hours, drips off, at-80 DEG C, continue stirring reaction after dripping off after 1 hour, slowly get back to room temperature, and at room temperature stirring reaction 24 hours; Be 0.5mol/L by the slow implantation concentration of reaction solution obtained, temperature is in 5 DEG C of cold dilute hydrochloric acids, with 100 revs/min of stirrings, with 1000 revs/min of stirrings after adding, and continue 30 minutes; Then use the extracted with diethyl ether twice of reaction solution volume 1/2, the organic phase of twice extraction is merged, wash one time with organic phase equal-volume deionized water and saturated sodium-chloride water solution respectively, separate organic phase, with anhydrous sodium sulfate drying 5 hours; Material after drying is revolved and steams except desolventizing, obtain solid matter, use the deionized water/methanol mixed solvent of volume ratio 5:1 by solid matter recrystallization 2 times, obtain off-white color compound 1,2-dihydro cyclobutene also [α] naphthalene-4-boric acid 83g, productive rate about 65%.
Embodiment 2:
By 1,2-dihydro cyclobutene also [α] naphthalene 300g, 90% glacial acetic acid 2500mL and methyl alcohol 250mL add in 5000mL low-temp reaction device, stir, after 1 hour, reaction solution be cooled to-8 DEG C; Bromine 300g is dissolved in 90% glacial acetic acid of 550ml, obtains bromine solution, at-8 DEG C, be added dropwise to reaction solution by bromine solution uniform speed slow while stirring reaction liquid, dripped off in 5 hours, drip off follow-up continuation of insurance temperature 2 hours, obtain reddish-brown reaction solution; The reddish-brown reaction solution obtained is transferred to 5000mL brown bottle, put into low-temp. refrigerator, react at-25 DEG C after 60 hours, brown bottle is taken out from low-temp. refrigerator under being placed in room temperature, make reacting liquid temperature reach room temperature, now reaction solution is yellow liquid, is again transferred in 8000mL reaction flask by the yellow reaction liquid obtained, add 3500mL dichloromethane extraction 2 times, separate organic phase; In addition 150g Sodium Metabisulfite is dissolved in wiring solution-forming in 2400ml deionized water, Sodium Metabisulfite solution is added in organic phase and stir 10 minutes, stratification, then use 2500mL deionization to wash one time, organic phase is separated, dry 5 hours, clear yellow viscous solid is obtained after organic phase is concentrated, the petrol ether/ethyl acetate mixed solvent recrystallization that use volume ratio is 6:1 2 times, obtains bromo-1, the 2-dihydro cyclobutene of faint yellow compound 4-also [α] naphthalene.
The potassium hydroxide solid adding mass ratio about 5% after being broken a seal by the AR level tetrahydrofuran (THF) newly bought carries out predrying, seal after suitable concussion and keep in Dark Place, after predrying 24 hours, solid settlement is in bottom, clear liquid is moved into round-bottomed flask, and press-in sodium silk, adds the benzophenone that mass ratio is 5 ‰, reflux to liquid steams after becoming mazarine, obtains dry tetrahydrofuran.
By obtained bromo-1, the 2-dihydro cyclobutene of 4-also [α] naphthalene 200g be dissolved in 1800mL brand-new dry tetrahydrofuran, obtain bromo-1, the 2-dihydro cyclobutene of 4-also [α] naphthalene solution;
Build the grignard reaction device of 5000ml, under pure nitrogen gas atmosphere protection, 100mL brand-new dry tetrahydrofuran is added in the reactor filling 20g magnesium chips and 0.01g initiator iodine grain, then at room temperature while stirring reaction by bromo-for 4-1.2-dihydro cyclobutene also [α] naphthalene solution instillation reactor, within 2 hours, drip off, be warming up to 70 DEG C after dripping and continue stirring reaction 2 hours; The reaction solution obtained is transferred in low-temp reaction device, at-100 DEG C, while stirring reaction, 90g trimethyl borate is slowly at the uniform velocity added dropwise to reaction solution, within 3 hours, drips off, at-100 DEG C, continue stirring reaction after dripping off after 2 hours, slowly get back to room temperature, and at room temperature stirring reaction 36 hours; Be 0.5mol/L by the slow implantation concentration of reaction solution obtained, temperature is in 10 DEG C of cold dilute hydrochloric acids, with 100 revs/min of stirrings, with 1000 revs/min of stirrings after adding, and continue 50 minutes; Then use the extracted with diethyl ether twice of reaction solution volume 1/2, the organic phase of twice extraction is merged, wash one time with organic phase equal-volume deionized water and saturated sodium-chloride water solution respectively, separate organic phase, with anhydrous sodium sulfate drying 5 hours; Material after drying is revolved and steams except desolventizing, obtain solid matter, use the deionized water/methanol mixed solvent of volume ratio 5:1 by solid matter recrystallization 2 times, obtain off-white color compound 1,2-dihydro cyclobutene is [α] naphthalene-4-boric acid 104g also, productive rate about 62%.
Embodiment 3:
By 1,2-dihydro cyclobutene also [α] naphthalene 300g, 90% glacial acetic acid 1700mL and methyl alcohol 200mL add in 5000mL low-temp reaction device, stir, after 3 hours, reaction solution be cooled to-10 DEG C; Bromine 300g is dissolved in 90% glacial acetic acid of 700ml, obtains bromine solution, at-10 DEG C, reaction solution is added dropwise to by bromine solution uniform speed slow while stirring reaction liquid, dripped off in 3 hours, drip off follow-up continuation of insurance temperature 3 hours, obtain reddish-brown reaction solution; The reddish-brown reaction solution obtained is transferred to 5000mL brown bottle, put into low-temp. refrigerator, react at-15 DEG C after 72 hours, brown bottle is taken out from low-temp. refrigerator under being placed in room temperature, make reacting liquid temperature reach room temperature, now reaction solution is yellow liquid, is again transferred in 8000mL reaction flask by the yellow reaction liquid obtained, add 3000mL dichloromethane extraction 2 times, separate organic phase; In addition 200g Sodium Metabisulfite is dissolved in wiring solution-forming in 3000ml deionized water, Sodium Metabisulfite solution is added in organic phase and stir 5 minutes, stratification, then wash one time with the isopyknic deionization of organic phase, organic phase is separated, dry 8 hours, clear yellow viscous solid is obtained after organic phase is concentrated, the petrol ether/ethyl acetate mixed solvent recrystallization that use volume ratio is 8:1 2 times, obtains bromo-1, the 2-dihydro cyclobutene of faint yellow compound 4-also [α] naphthalene.
The potassium hydroxide solid adding mass ratio about 5% after being broken a seal by the AR level tetrahydrofuran (THF) newly bought carries out predrying, seal after suitable concussion and keep in Dark Place, after predrying 24 hours, solid settlement is in bottom, clear liquid is moved into round-bottomed flask, and press-in sodium silk, adds the benzophenone that mass ratio is 5 ‰, reflux to liquid steams after becoming mazarine, obtains dry tetrahydrofuran.
By obtained bromo-1, the 2-dihydro cyclobutene of 4-also [α] naphthalene 200g be dissolved in 2000mL brand-new dry tetrahydrofuran, obtain bromo-1, the 2-dihydro cyclobutene of 4-also [α] naphthalene solution;
Build the grignard reaction device of 5000ml, under pure nitrogen gas atmosphere protection, 100mL brand-new dry tetrahydrofuran is added in the reactor filling 20g magnesium chips and 0.02g initiator iodine grain, then at room temperature while stirring reaction by bromo-for 4-1.2-dihydro cyclobutene also [α] naphthalene solution instillation reactor, within 3 hours, drip off, be warming up to 60 DEG C after dripping and continue stirring reaction 3 hours; The reaction solution obtained is transferred in low-temp reaction device, at-70 DEG C, while stirring reaction, 90g trimethyl borate is slowly at the uniform velocity added dropwise to reaction solution, within 2 hours, drips off, at-70 DEG C, continue stirring reaction after dripping off after 3 hours, slowly get back to room temperature, and at room temperature stirring reaction 24 hours; Be 0.4mol/L by the slow implantation concentration of reaction solution obtained, temperature is in 5 DEG C of cold dilute hydrochloric acids, with 100 revs/min of stirrings, with 1000 revs/min of stirrings after adding, and continue 30 minutes; Then use the extracted with diethyl ether twice of reaction solution volume 1/2, the organic phase of twice extraction is merged, wash one time with organic phase equal-volume deionized water and saturated sodium-chloride water solution respectively, separate organic phase, with anhydrous sodium sulfate drying 8 hours; Material after drying is revolved and steams except desolventizing, obtain solid matter, use the deionized water/methanol mixed solvent of volume ratio 6:1 by solid matter recrystallization 2 times, obtain off-white color compound 1,2-dihydro cyclobutene is [α] naphthalene-4-boric acid 115g also, productive rate about 68%.
Although embodiment of the present invention are open as above, but it is not restricted to listed in specification sheets and embodiment utilization, it can be applied to various applicable the field of the invention completely, for those skilled in the art, can easily realize other amendment, therefore do not deviating under the universal that claim and equivalency range limit, the present invention is not limited to specific details and illustrates here and the legend described.
Claims (10)
1.1,2-dihydro cyclobutene is [α] naphthalene-4-boronic acid compounds also, and it is characterized in that, chemical structural formula is:
2. the preparation method of 1, a 2-dihydro cyclobutene according to claim 1 also [α] naphthalene-4-boronic acid compounds, is characterized in that, comprise the steps:
Step one, with 1,2-dihydro cyclobutene also [α] naphthalene is that 4-bromo-1 prepared by raw material, 2-dihydro cyclobutene is [α] naphthalene also, then by obtained 4-bromo-1,2-dihydro cyclobutene also [α] naphthalene is dissolved in dry tetrahydrofuran, obtain bromo-1, the 2-dihydro cyclobutene of 4-also [α] naphthalene solution;
Step 2, under pure nitrogen gas atmosphere protection, dry tetrahydrofuran is added in the reactor filling magnesium chips and initiator iodine grain, then the 4-bromo-1 at room temperature step one obtained while stirring reaction, 2-dihydro cyclobutene is [α] naphthalene solution instillation reactor also, within 2 ~ 3 hours, drip off, be warming up to 50 ~ 70 DEG C after dripping and continue stirring reaction 1 ~ 3 hour;
Step 3, reaction solution step 2 obtained are transferred in low-temp reaction device, at-100 ~-60 DEG C, while stirring reaction, trimethyl borate is slowly at the uniform velocity added dropwise to reaction solution, within 2 ~ 3 hours, drip off, at-100 ~-60 DEG C, stirring reaction is continued after 1 ~ 3 hour after dripping off, slowly get back to room temperature, and at room temperature stirring reaction 12 ~ 36 hours;
Step 4, a certain amount of dilute hydrochloric acid is chilled to 0 ~ 10 DEG C in advance in refrigerator after, reaction solution step 3 obtained slowly injects this cold dilute hydrochloric acid, slowly stirs, add rear acceleration stir, and continue 20 ~ 50 minutes;
Step 5, reaction solution twice by extracted with diethyl ether step 4, merged the organic phase of twice extraction, wash one time respectively, separate organic phase with organic phase equal-volume deionized water and saturated sodium-chloride water solution, with anhydrous sodium sulfate drying 4 ~ 8 hours;
Step 6, material after drying revolved and steams except desolventizing, obtain solid matter, use deionized water/methanol mixed solvent by solid matter recrystallization 2 times, obtain compound 1,2-dihydro cyclobutene also [α] naphthalene-4-boric acid.
3. according to claim 21, the preparation method of 2-dihydro cyclobutene also [α] naphthalene-4-boronic acid compounds, it is characterized in that, 4-bromo-1 in step one, the preparation method of 2-dihydro cyclobutene also [α] naphthalene is: by weight ratio be 1:6 ~ 10 1,2-dihydro cyclobutene also [α] naphthalene and glacial acetic acid add in low-temp reaction device, add methyl alcohol simultaneously, wherein the volume ratio of methyl alcohol and glacial acetic acid is 1:8 ~ 12, stirs, after 1 ~ 3 hour, reaction solution is cooled to-10 ~ 0 DEG C; In addition be bromine and the glacial acetic acid mixed dissolution of 1:4 ~ 7 by mol ratio, obtain bromine solution, at-10 ~ 0 DEG C, reaction solution is added dropwise to by bromine solution uniform speed slow while stirring reaction liquid, dripped off in 2 ~ 5 hours, drip off follow-up continuation of insurance temperature 1 ~ 3 hour, obtain reddish-brown reaction solution; Put into low-temp. refrigerator by after reddish-brown reaction solution lucifuge, react after 48 ~ 72 hours at-30 ~-15 DEG C, reaction solution is taken out from low-temp. refrigerator under being placed in room temperature, make reacting liquid temperature reach room temperature; The reaction solution reaching room temperature is added the dichloromethane extraction 2 times of 1 ~ 3 times of reaction solution volume, separate organic phase; In addition be add in organic phase after the Sodium Metabisulfite of 1:15 ~ 25 and deionized water wiring solution-forming to stir 5 ~ 10 minutes by weight ratio, stratification, then uses and washes one time with the isopyknic deionization of organic phase, organic phase separated, dry 4 ~ 8 hours, after concentrated, obtain sticky solid; Use volume ratio to be the sherwood oil of 5 ~ 10:1 and ethyl acetate mixed solvent by sticky solid recrystallization 2 times, obtain bromo-1, the 2-dihydro cyclobutene of faint yellow compound 4-also [α] naphthalene.
4. according to claim 21, the preparation method of 2-dihydro cyclobutene also [α] naphthalene-4-boronic acid compounds, it is characterized in that, in step one and step 2, dry tetrahydrofuran is the dry tetrahydrofuran newly steamed, its drying means is: the potassium hydroxide solid adding mass ratio about 5% after being broken a seal by AR level tetrahydrofuran (THF), seal after suitable concussion and keep in Dark Place, after predrying 24 hours, clear liquid is moved into round-bottomed flask, press-in sodium silk, adding mass ratio is 2 ~ 5 ‰ benzophenone, and reflux to liquid steams after becoming mazarine, obtains dry tetrahydrofuran.
5. the preparation method of 1,2-dihydro cyclobutene according to claim 2 also [α] naphthalene-4-boronic acid compounds, is characterized in that, in step one, the weight ratio of bromo-1, the 2-dihydro cyclobutene of 4-also [α] naphthalene and dry tetrahydrofuran is 1:6 ~ 10.
6. according to claim 21, the preparation method of 2-dihydro cyclobutene also [α] naphthalene-4-boronic acid compounds, it is characterized in that, 4-bromo-1 in magnesium chips and step one in step 2, the mol ratio of 2-dihydro cyclobutene also [α] naphthalene is 1 ~ 1.1:1, the consumption of initiator iodine grain is 0.01 ~ 0.02g, and the volume adding dry tetrahydrofuran accounts for 1/50 of reactor capacity.
7. the preparation method of 1,2-dihydro cyclobutene according to claim 2 also [α] naphthalene-4-boronic acid compounds, is characterized in that, the mol ratio of step 3 mesoboric acid trimethyl and bromo-1, the 2-dihydro cyclobutene of 4-also [α] naphthalene is 1 ~ 1.1:1.
8. according to claim 21, the preparation method of 2-dihydro cyclobutene also [α] naphthalene-4-boronic acid compounds, it is characterized in that, the concentration of dilute hydrochloric acid described in step 4 is 0.3 ~ 0.5mol/L, consumption is 2 ~ 3 times of the reaction solution volume that step 3 obtains, the speed of described slow stirring is 100 revs/min, accelerates the speed 1000 revs/min stirred.
9. the preparation method of 1,2-dihydro cyclobutene according to claim 2 also [α] naphthalene-4-boronic acid compounds, it is characterized in that, in step 5, the volume of ether is 1/2 of reaction solution volume.
10. according to claim 21, the preparation method of 2-dihydro cyclobutene also [α] naphthalene-4-boronic acid compounds, it is characterized in that, in step 6, the volume ratio of deionized water/methyl alcohol is 5 ~ 10:1, the color of the solid matter obtained is grey, the color of 1, the 2-dihydro cyclobutene obtained also [α] naphthalene-4-boronic acid compounds is off-white color.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410603576.7A CN104447826A (en) | 2014-10-30 | 2014-10-30 | 1,2-dihydrocyclobuteno[alpha]naphthyridine-4-boronic acid compound and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410603576.7A CN104447826A (en) | 2014-10-30 | 2014-10-30 | 1,2-dihydrocyclobuteno[alpha]naphthyridine-4-boronic acid compound and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104447826A true CN104447826A (en) | 2015-03-25 |
Family
ID=52894640
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410603576.7A Pending CN104447826A (en) | 2014-10-30 | 2014-10-30 | 1,2-dihydrocyclobuteno[alpha]naphthyridine-4-boronic acid compound and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104447826A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPWO2015133437A1 (en) * | 2014-03-03 | 2017-04-06 | 三菱化学株式会社 | Polymer, composition for organic electroluminescence device, organic electroluminescence device, organic EL display device and organic EL lighting |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4898999A (en) * | 1988-06-03 | 1990-02-06 | Shell Oil Company | Process for halogenating cyclobutenoarenes |
| WO1997033193A2 (en) * | 1996-02-23 | 1997-09-12 | The Dow Chemical Company | Cross-linkable or chain extendable polyarylpolyamines and films thereof |
| CN101434513A (en) * | 2007-11-15 | 2009-05-20 | 上海三爱思试剂有限公司 | Preparation of 1-naphthalene bromide |
| CN103626621A (en) * | 2013-12-11 | 2014-03-12 | 绵阳高新区达高特科技有限公司 | Novel synthetic method of 1,2-dihydro cyclobutene [alpha] naphthalene |
| CN103819308A (en) * | 2014-03-13 | 2014-05-28 | 中国科学院上海有机化学研究所 | Solidifiable poly-meta-phenylene as well as preparation method and application thereof |
-
2014
- 2014-10-30 CN CN201410603576.7A patent/CN104447826A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4898999A (en) * | 1988-06-03 | 1990-02-06 | Shell Oil Company | Process for halogenating cyclobutenoarenes |
| WO1997033193A2 (en) * | 1996-02-23 | 1997-09-12 | The Dow Chemical Company | Cross-linkable or chain extendable polyarylpolyamines and films thereof |
| CN101434513A (en) * | 2007-11-15 | 2009-05-20 | 上海三爱思试剂有限公司 | Preparation of 1-naphthalene bromide |
| CN103626621A (en) * | 2013-12-11 | 2014-03-12 | 绵阳高新区达高特科技有限公司 | Novel synthetic method of 1,2-dihydro cyclobutene [alpha] naphthalene |
| CN103819308A (en) * | 2014-03-13 | 2014-05-28 | 中国科学院上海有机化学研究所 | Solidifiable poly-meta-phenylene as well as preparation method and application thereof |
Non-Patent Citations (3)
| Title |
|---|
| BONGSOO KIM: ""Molecular Tunnel Junctions Based on π-Conjugated Oligoacene Thiols and Dithiols between Ag,Au,and Pt Contacts: Effect of Surface Linking Group and Metal Work Function"", 《J.AM.CHEM.SOC.》 * |
| J.M.BLATCHLY等: "Biphenylenes. Part XXV. 2-Benzoylbiphenylenes and the synthesis of Biphenylene-2-boronic and 2,6-(or 2,7-)diboronic acid", 《J.CHEM.SOC.》, 1 January 1969 (1969-01-01), pages 2789 - 2793 * |
| 刑其毅 等著: "《基础有机化学 （第三版）》", 30 June 2005, article "第11.8节 卤化反应", pages: 472-475 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPWO2015133437A1 (en) * | 2014-03-03 | 2017-04-06 | 三菱化学株式会社 | Polymer, composition for organic electroluminescence device, organic electroluminescence device, organic EL display device and organic EL lighting |
| JP2019173032A (en) * | 2014-03-03 | 2019-10-10 | 三菱ケミカル株式会社 | Polymer, composition for organic electroluminescent elements, organic electroluminescent element, organic el display device and organic el illumination |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104292145A (en) | Preparation method of 6-bromoindole derivative | |
| CN110041361A (en) | Photocatalysis allylation/Cyclopropanated tandem reaction synthesis bis- substituted cyclopropane of 1,1- method | |
| CN106222218A (en) | A kind of enzyme process prepares the method for rhodioside | |
| CN101270049B (en) | Method of preparing cydia molesta sex pheromone | |
| CN104447826A (en) | 1,2-dihydrocyclobuteno[alpha]naphthyridine-4-boronic acid compound and preparation method thereof | |
| CN104447191B (en) | Bromo-1, the 2-dihydro cyclobutene of 4-also [α] naphthalene compound and preparation method thereof | |
| CN105713063A (en) | Abiraterone acetate preparation method | |
| CN102180914A (en) | Preparation method of 2-deoxidizing-D-glucose | |
| CN107721836A (en) | One kind synthesis 1,7 2（4 hydroxy phenyls）The method of the ketone of 1,4 diene of heptane 3 | |
| CN104478974B (en) | A kind of 20, the synthetic method of 23-dipiperidino-5-O-mycamino syl-tylono lide | |
| CN102558142A (en) | Preparation method of alpha-lipoic acid bulk pharmaceutical | |
| CN107235853B (en) | A kind of synthetic method being used to prepare Canton love-pea vine A prime and its isomers | |
| CN104693025A (en) | Feeding manner for preparing L-monomenthyl glutarate | |
| CN105001135A (en) | Chemical synthetic method for raphanin | |
| CN106699605B (en) | A kind of methylation method of scheme for lacosamide intermediate | |
| WO2008116387A1 (en) | A preparation process for taxol and derivatives thereof | |
| CN106674177A (en) | Synthesis method of 7-acryloyloxy-4-methylcoumarin | |
| CN109206419A (en) | Sha Ku is than bent intermediate and its preparation method and application | |
| CN113354601A (en) | Preparation method of beta-propiolactone | |
| CN103601781B (en) | Prepare the method that 19-removes first-5 (10)-androsterone compound | |
| CN105175425B (en) | A kind of method that high-purity chlorin is prepared from blunt top spirulina | |
| CN102079691A (en) | Method for synthesizing trans-resveratrol by combining hydroxyl groups and protective groups | |
| CN103804147A (en) | Preparation method of 4-hydroxyphenethyl alcohol | |
| CN102408336B (en) | Method for preparing strontium ranelate intermediate | |
| CN103387597B (en) | Preparation method of abiraterone acetic ester |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20150325 |