CN101928275B - Preparation technology of 4'4'' (5'')-di-tert-butyl-di-benzo-18-crown-6 - Google Patents
Preparation technology of 4'4'' (5'')-di-tert-butyl-di-benzo-18-crown-6 Download PDFInfo
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- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims abstract description 42
- 238000006243 chemical reaction Methods 0.000 claims abstract description 33
- 239000000203 mixture Substances 0.000 claims abstract description 33
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- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims abstract description 20
- 229910000024 caesium carbonate Inorganic materials 0.000 claims abstract description 19
- 239000002904 solvent Substances 0.000 claims abstract description 17
- 238000000926 separation method Methods 0.000 claims abstract description 16
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- 238000000746 purification Methods 0.000 claims abstract description 12
- 239000000741 silica gel Substances 0.000 claims abstract description 12
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- 239000002994 raw material Substances 0.000 claims abstract description 5
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 48
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- 239000003480 eluent Substances 0.000 claims description 22
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 15
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- 238000000034 method Methods 0.000 abstract description 16
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- 239000003795 chemical substances by application Substances 0.000 abstract description 8
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- 230000015572 biosynthetic process Effects 0.000 abstract description 3
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- 239000000706 filtrate Substances 0.000 description 21
- 238000005303 weighing Methods 0.000 description 21
- 239000000047 product Substances 0.000 description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 11
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- ZZXDRXVIRVJQBT-UHFFFAOYSA-M Xylenesulfonate Chemical compound CC1=CC=CC(S([O-])(=O)=O)=C1C ZZXDRXVIRVJQBT-UHFFFAOYSA-M 0.000 description 7
- 150000003983 crown ethers Chemical class 0.000 description 7
- 238000000605 extraction Methods 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 238000001953 recrystallisation Methods 0.000 description 7
- 229940071104 xylenesulfonate Drugs 0.000 description 7
- 241000143437 Aciculosporium take Species 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
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- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
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- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
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- -1 aromatic series crown ether Chemical class 0.000 description 2
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Abstract
The invention discloses a preparation technology of 4'4'' (5'')-di-tert-butyl-di-benzo-18-crown-6, which is characterized by comprising the following steps: selecting para-tert-butylcatechol as a raw material, caesium carbonate as a template agent, and tetrahydrofuran or acetonitrile as a solvent, adding the reaction materials to an agitated reactor, and synthesizing to obtain a mixture containing the expected product 4'4'' (5'')-di-tert-butyl-di-benzo-18-crown-6 at 40-80 DEG C under the protection of nitrogen atmosphere; and after finishing the reaction, adopting a silica gel alumina backflow co-heat technology or an eluant with different compositions and proportioning to perform column chromatography gradient elution, and isolating and purifying the expected product 4'4'' (5'')-di-tert-butyl-di-benzo-18-crown-6. Compared with the reportorial preparation technology, the invention simplifies the procedures of synthesis as well as separation and purification and improves the reaction conversion rate and the purity and yield of the products.
Description
Technical field
The present invention relates to a kind of crown compound 4 ' 4 " the new synthetic and separation purifying technique of (5 ")-di-t-butyl dibenzo-18-hat-6, belong to technical field of organic synthesis.
Background technology
Because the macrocyclic structure of crown compound has specific selectivity to metal ion, especially basic metal and alkaline earth metal is shown superpower selectivity and mating capability, has become from high activity liquid waste in the last few years and has removed
137One of study hotspot of the isotopic ions such as Cs.
Simple aliphatics or aromatic series crown ether are generally synthetic by the Williamson reaction by diphenol and multiethylene-glycol (glycol) or multiethylene-glycol dihalide.The ether cave size of the required general crown ether according to synthesizing of template alkali is decided in the reaction, and common alkali is sodium hydroxide, potassium hydroxide etc.Common solvent is generally the protic straight chain alcohols such as propyl carbinol.The method of the separation and purification of simple crown ether is also comparatively simple and easy, only needs the acetone precipitating just can obtain the product of higher degree such as dibenzo-18-hat-6.
With the complicated crown compound of alkyl group side chain, for example 4 ' 4 " (5 ")-di-t-butyl dibenzo-18-hat-6 has that extracting power is strong, a high advantage of solubleness in the non-polar solvent, but the equal difficulty relatively of its synthetic and separation and purification.Reported 4 ' 4 " (5 ")-di-t-butyl dibenzo-18-hat-6 synthetic methods are to synthesize first the dibenzo of not being with tertiary butyl side chain-18-hat 6, again take the trimethyl carbinol or uncle's butane halogenide as alkylating agent, the strong acid such as PPA or the vitriol oil are that solvent carries out St reaction in benzene and prepares.Synthetic route is as follows:
The first step, take pyrocatechol as raw material, NaOH is alkali, propyl carbinol is the synthetic dibenzo of solvent and Dichlorodiethyl ether-18-hat 6.
Second step, take the trimethyl carbinol as alkylating agent and dibenzo-18-hat 6 reaction synthetic 4 ' 4 in strong acid " (5 ")-di-t-butyl dibenzo-18-hat-6.
This synthetic method belongs to St reaction in benzene, because the substituting group tertiary butyl has activation to phenyl ring.After first tertiary butyl replaced successfully, the adjacency pair position of place phenyl ring was activated, thereby is very easily replaced by other tertiary butyls, formed the dibenzo 18-hat-6 of many tertiary butyls.So it is wayward that the shortcoming of the method is to introduce number and the position of the tertiary butyl, be difficult to form the symmetrical compound that replaces, by product is many, similar performance is difficult to separation.Used strongly-acid solvent corrosive equipment is high to equipment requirements.The toxicity of alkylating agent is larger, and human body and environment are all had larger harm.
About 4 ' 4 " separation purification method of (5 ")-di-t-butyl dibenzo-18-hat-6, the document of having reported adopts the ion complexation extraction process.The liquid phase mixture that the method at first need dispose definite composition is as complexing agent, and this mixture contains the predetermined extraction agent except requiring, and also need contain one or more are dissolved in organic thinner in addition as solute extraction agent.Each extraction agent not only requires complexity, and selects difficulty, and the metal-salt in the extraction agent such as cesium chloride price are higher, and cost increases thus.In the said extracted agent, add the mixture that building-up reactions obtains, for a long time reaction makes the metal ion and 4 ' 4 in the extraction agent under the certain temperature " (5 ")-di-t-butyl dibenzo-18-hat-6 formation complex compounds.Complicated because of the mix ingredients that building-up reactions obtains, the metal ion in the extraction agent there is interference effect, so the complex reaction low conversion rate, clathrate separation is also comparatively difficult, is difficult to obtain the higher complex compound of purity.The method also needs the specific complexing solvent of separating in addition, makes 4 ' 4 by the certain condition reaction " (5 ")-di-t-butyl dibenzo-18-hat-6 separates complexing with metal ion, to isolate 4 ' 4 " (5 ")-di-t-butyl dibenzo-18-hat-6.The same with complexing solvent, separate complexing solvent many requirements are also arranged, the preparation difficulty, and decomplexing interflow journey is loaded down with trivial details, the impurity of bringing into when separating complex compound is difficult to remove, final gained 4 ' 4 " (5 ")-the di-t-butyl dibenzo-18-hat-6 yields are lower, purity is not high, and the flow process very complicated, time is longer, and cost is higher.
Therefore, develop new synthetic and separating technology, improve 4 ' 4 " reaction conversion ratio of (5 ")-di-t-butyl dibenzo-18-hat-6, simplify synthetic and separation and purification flow process, improve research emphasis and difficult point that product yield and purity become crown ether synthetic chemistry field.
Summary of the invention
The object of the invention is to overcome described in the background technology 4 ' 4 " deficiency of the synthetic and purifying process of (5 ")-di-t-butyl dibenzo-18-hat-6, provide a kind of new 4 ' 4 " (5 ")-di-t-butyl dibenzo-18-hat-6 synthetic and purifying process, to improve the purity of reaction conversion ratio and purpose product, simplification of flowsheet.
For reaching above purpose, the present invention takes following technical scheme to be achieved:
The preparation technology of a kind of 4 ' 4 " (5 ")-di-t-butyl dibenzo-18-hat-6; it is characterized in that; selecting p-ten.-butylcatechol is raw material; selecting cesium carbonate is template; selecting tetrahydrofuran (THF) or acetonitrile is solvent; the initial molar fraction of p-ten.-butylcatechol is 0.1-0.25mol/l; with the mol ratio of cesium carbonate be 1: 2.2-3; above reaction mass is added in the reactor; and protect with nitrogen atmosphere; 100 ℃ lower synthetic obtains containing purpose products 4 ' 4 " mixture of (5 ")-di-t-butyl dibenzo-18-hat-6, reaction formula is as follows:
After reaction finishes, adopt the backflow of silica gel aluminum oxide to be total to thermal process and come the separation and purification mixture; Perhaps dispose eluent, carry out the column chromatography gradient elution and come the separation and purification mixture, obtain at last purifying 4 ' 4 " (5 ")-di-t-butyl dibenzo-18-hat-6.
In the such scheme, described temperature of reaction is 40 ℃-80 ℃.Described silica gel aluminum oxide refluxes and is total in the thermal process, and selecting normal heptane or normal hexane is solvent, and feed ratio is solvent: silica gel or aluminum oxide: mixture=10-100ml: 5-50g: 1g, and at 60 ℃-90 ℃ lower altogether hot 2-12h that reflux.Described column chromatography gradient elution is three times, and by volume, primary eluent consists of sherwood oil: ethyl acetate: methylene dichloride=1: 0.8-1.2: 0.1-0.3; Secondary eluent consists of sherwood oil: acetone: methylene dichloride=1: 0.5-1.2: 0.05-0.2; Eluent for the third time consists of sherwood oil: methyl alcohol: methylene dichloride=1: 0.1-0.3: 0.1-0.3.The mass ratio of mixture and post layer silica gel is 1 in the described column chromatography gradient elution: 30-100.
The present invention compared with prior art, the p-ten.-butylcatechol of at first choosing with tertiary butyl side chain is raw material, determines replacement number and the position of the tertiary butyl in the product, has overcome the shortcomings that the location of substituting group in the phenyl ring electrophilic substitution method is inaccurate and by product is many; Choosing cesium carbonate is template, utilizes Cs
+Radius and 4 ' 4 " the crown ether cycle radius matches in (5 ")-di-t-butyl dibenzo-18-hat-6 characteristics, promoted the formation of crown ether cycle; Choosing tetrahydrofuran (THF) or acetonitrile is solvent, weakened protic solvent to the solvation of the negatively charged ion of nucleophilic reagent p-ten.-butylcatechol with to the detrimentally affect of the cation activity of template, concentration and the cation activity of effective negatively charged ion have been improved, the final transformation efficiency that improves reaction.
High performance liquid phase map analysis by thick product as can be known, mainly contain five kinds of materials in the mixture that obtains after reaction finishes, be respectively little linear fragment, 4 ' 4 " (5 ")-di-t-butyl dibenzo-18-hat-6, little cyclic ethers, the polymeric ether that contains phenyl ring and quinones.Molecular structure is as follows successively:
Its polarity size is little linear fragment＜4 ' 4 " (5 ")-di-t-butyl dibenzo-18-hat-6＜little cyclic ethers＜contain polymeric ether＜quinones of phenyl ring, and the polarity of 4 ' 4 " (5 ")-di-t-butyl dibenzo-18-hat-6 is very similar to little cyclic ethers, therefore, selecting the eluent of single proportioning to be difficult to other by products and 4 ' 4 " (5 ")-di-t-butyl dibenzo-18-is preced with-6 minutes and opens.
The present invention further improves and is, at first chooses the low polarity eluent of petroleum ether-ethyl acetate-methylene dichloride composition and isolates little linear fragment.By choosing the higher mixtures of eluents sherwood oil-acetone of polarity-methylene dichloride, isolate a part of 4 ' 4 again " (5 ")-di-t-butyl dibenzo-18-hat-6.Continue to improve eluent polarity, the eluent of selecting sherwood oil-methyl alcohol-methylene dichloride to form is isolated another part 4 ' 4 " (5 ")-di-t-butyl dibenzo-18-hat-6.Can obtain purity up to 4 ' 4 more than 80% " (5 ")-di-t-butyl dibenzo-18-hat-6.All the other by products then finally soak by methyl alcohol, in the lump stripping.Utilize like this gradient elution of polarity difference, the purpose product is recycled with higher degree.
The silica gel aluminum oxide refluxes altogether, and thermal process mainly is to utilize hot conditions, make quinones and with benzene ring compound and the alkali alumina generation irreversible adsorption of phenolic hydroxyl group, little linear fragment and phenyl ring polymeric ether continue polymerization and form macromole and silica gel adsorbed close, thereby the most of by product of disposable removal, reduced the product loss, yield can reach 50%-60%.
With the complexing abstraction of having reported for work relatively, two kinds of separation methods proposed by the invention have improved 4 ' 4 " purity and the yield of (5 ")-di-t-butyl dibenzo-18-hat-6.
Description of drawings
Fig. 1 is 4 ' 4 " infrared spectrum of (5 ")-di-t-butyl dibenzo-18-hat-6 standard substance.As shown in the figure, 1589,1519 and 1455cm
-1About the peak be the skeletal vibration charateristic avsorption band of phenyl ring; 1414cm
-1C-H stretching vibration absorption peak for phenyl ring; 897,858 and 802cm
-1C-H wagging vibration absorption peak for the replacement of phenyl ring Isosorbide-5-Nitrae position; 1266,1216 and 1147cm
-1Stretching vibration vibration for crown ether cycle C-O-C; 2960 and 2871cm
-1Be tertiary butyl CH
3Or CH
2In c h bond stretching vibration absorption peak.
Fig. 2 be the embodiment of the invention 2 preparation 4 ' 4 " infrared spectrum of (5 ")-di-t-butyl dibenzo-18-hat-6 high sterling of gained after repeatedly repeatedly purifying.By finding out that with Fig. 1 contrast position and the intensity of two collection of illustrative plates charateristic avsorption bands are basic identical, can assert that this compound is with 4 ' 4 " all specific functional groups of (5 ")-di-t-butyl dibenzo-18-hat-6.
Fig. 3 is 4 ' 4 " (5 ")-di-t-butyl dibenzo-18-is preced with-6 standard substance
1H-NMR spectrogram, solvent are CDCl
3As shown in the figure, according to the peak position as can be known peak 1 be H on the phenyl ring; Peak 2 is the H on the crown ether cycle; Peak 3 is the H on the tertiary butyl; Peak 4 is lock peaks.Peak 1,2 and 3 integral area ratio are about 3: 8: 9, with 4 ' 4 " in (5 ")-di-t-butyl dibenzo-18-hat-6 number of three kinds of H than consistent.
Fig. 4 be the embodiment of the invention 2 preparation 4 ' 4 " (5 ")-di-t-butyl dibenzo-18-hat-6 high sterling of gained after repeatedly repeatedly purifying
1The H-NMR spectrogram, solvent is similarly CDCl
3Can find out that with Fig. 3 contrast the peak 1 among Fig. 4,2 and 3 position and integral area and Fig. 3 are in full accord, integral area ratio meets 4 ' 4 for being 3: 8: 9 also " (5 ")-di-t-butyl dibenzo-18-is preced with the number ratio of three kinds of H in-6.In conjunction with Fig. 1 and Fig. 2, can determine that this compound is 4 ' 4 again " (5 ")-di-t-butyl dibenzo-18-hat-6.
Embodiment
The present invention is described in further detail below in conjunction with specific embodiment.
A. take by weighing respectively p-ten.-butylcatechol 8.3g (0.05mol) and cesium carbonate 35.8g (0.11mol) is dissolved in the 500ml tetrahydrofuran (THF), wherein cesium carbonate at twice equivalent add.Take by weighing a certain amount of glycol ether xylene sulfonate, be dissolved at twice the 250ml tetrahydrofuran (THF), place constant pressure funnel to drip.60 ℃ of lower reaction 48h, reaction conversion ratio 52.3%.
B. will filter according to the mixture that above-mentioned steps a reaction obtains, get filtrate vacuum distilling.Methyl alcohol stripping raffinate filters, and gets filtrate vacuum distilling.Methylene dichloride stripping raffinate, with the sodium thiosulfate solution repetitive scrubbing of 1N HCl and heat, separatory is got organic phase, and is stand-by behind the anhydrous magnesium sulfate drying.
C. take by weighing the mixture 5g that processed according to above-mentioned steps b, add 250g alkali alumina and 500ml normal hexane, 60 ℃ of lower altogether thermal response 2h that reflux cross leaching filtrate, vacuum distilling filtrate.Repeat this step until the filtrate clarification.Recrystallization in the low temperature bath, yield 53.1%, purity 65.9%.
Embodiment 2
A. take by weighing respectively p-ten.-butylcatechol 8.3g (0.05mol) and cesium carbonate 37.6g (0.115mol) is dissolved in the 400ml tetrahydrofuran (THF), wherein cesium carbonate at twice equivalent add.Take by weighing a certain amount of glycol ether xylene sulfonate, be dissolved at twice the 200ml tetrahydrofuran (THF), and place constant pressure funnel to drip.50 ℃ of lower reaction 36h, reaction conversion ratio 43.8%.
B. will filter according to the mixture that above-mentioned steps a obtains, get filtrate vacuum distilling.Methyl alcohol stripping raffinate continues to filter, and gets filtrate vacuum distilling again.Methylene dichloride stripping raffinate, with the sodium thiosulfate solution repetitive scrubbing of 1N HCl and heat, separatory is got organic phase, and is stand-by behind the anhydrous magnesium sulfate drying.
C. take by weighing 200-300 purpose column chromatography silica gel 100g, dry column-packing.Take by weighing the mixture 1g that processed according to above-mentioned steps b as the sample loading.Select first and consist of sherwood oil: ethyl acetate: the eluent of methylene dichloride=1: 0.8: 0.1 carries out wash-out; Select and consist of sherwood oil: acetone: the eluent of methylene dichloride=1: 0.5: 0.05 carries out wash-out, selects at last to consist of sherwood oil: methyl alcohol: the eluent of methylene dichloride=1: 0.1: 0.1 carries out wash-out.Repeat this gradient elution, until wash out contain in the mixture all 4 ' 4 " (5 ")-di-t-butyl dibenzo-18-hat-6.Collection is dissolved with the elutant of purpose product, and vacuum distilling is with pouring in the normal heptane that boils the temperature programmed control recrystallization behind the methylene dichloride stripping raffinate into.Yield 18.3%, purity 85.7%.
A. take by weighing respectively p-ten.-butylcatechol 8.3g (0.05mol) and cesium carbonate 40.6g (0.125mol) is dissolved in the 300ml tetrahydrofuran (THF), wherein cesium carbonate at twice equivalent add.Take by weighing a certain amount of glycol ether xylene sulfonate, be dissolved at twice the 150ml tetrahydrofuran (THF), and place constant pressure funnel to drip.40 ℃ of lower reaction 24h, reaction conversion ratio 33.7%.
B. will filter according to the mixture that above-mentioned steps a obtains, get filtrate vacuum distilling.Methyl alcohol stripping raffinate continues to filter, and gets filtrate vacuum distilling again.Methylene dichloride stripping raffinate, with the sodium thiosulfate solution repetitive scrubbing of 1N HCl and heat, separatory is got organic phase, and is stand-by behind the anhydrous magnesium sulfate drying.
C. take by weighing 200-300 purpose column chromatography silica gel 60g, dry column-packing.Take by weighing the mixture 1g that processed according to above-mentioned steps b as the sample loading.Select first and consist of sherwood oil: ethyl acetate: the eluent of methylene dichloride=1: 1.2: 0.3 carries out wash-out; Select and consist of sherwood oil: acetone: the eluent of methylene dichloride=1: 1.2: 0.2 carries out wash-out; Select at last and consist of sherwood oil: methyl alcohol: the eluent of methylene dichloride=1: 0.3: 0.3 carries out wash-out.Repeat this gradient elution, until wash out contained all 4 ' 4 in the mixture " (5 ")-di-t-butyl dibenzo-18-hat-6.Collection is dissolved with the elutant of purpose product, and vacuum distilling is with pouring in the normal heptane that boils the temperature programmed control recrystallization behind the methylene dichloride stripping raffinate into.Yield 22.1%, purity 77.5%.
A. take by weighing respectively p-ten.-butylcatechol 8.3g (0.05mol) and cesium carbonate 48.75 (0.15mol) is dissolved in the 500ml acetonitrile, wherein cesium carbonate at twice equivalent add.Take by weighing a certain amount of glycol ether xylene sulfonate at twice equivalent be dissolved in the 250ml acetonitrile, place constant pressure funnel to drip.80 ℃ of lower reaction 48h, reaction conversion ratio 37.6%.
B. will filter according to the mixture that above-mentioned steps a obtains, get filtrate vacuum distilling.Methyl alcohol stripping raffinate continues to filter, and gets filtrate vacuum distilling again.Methylene dichloride stripping raffinate, with the sodium thiosulfate solution repetitive scrubbing of 1N HCl and heat, separatory is got organic phase, and is stand-by behind the anhydrous magnesium sulfate drying.
C. take by weighing the mixture 5g that processed according to above-mentioned steps b, add 25g tlc silica gel and 50ml normal heptane, 70 ℃ of lower altogether thermal response 12h that reflux cross leaching filtrate, vacuum distilling filtrate.Repeat this step until the filtrate clarification.Recrystallization in the low temperature bath, yield 66.4%, purity 53.6%.
Embodiment 5
A. take by weighing respectively p-ten.-butylcatechol 8.3g (0.05mol) and cesium carbonate 42.25g (0.13mol) is dissolved in the 350ml acetonitrile, wherein cesium carbonate at twice equivalent add.Take by weighing a certain amount of glycol ether xylene sulfonate at twice equivalent be dissolved in the 175ml acetonitrile, place constant pressure funnel to drip.70 ℃ of lower reaction 36h, reaction conversion ratio 35.2%.
B. will filter according to the mixture that above-mentioned steps a obtains, get filtrate vacuum distilling.Methyl alcohol stripping raffinate continues to filter, and gets filtrate vacuum distilling again.Methylene dichloride stripping raffinate, with the sodium thiosulfate solution repetitive scrubbing of 1N HCl and heat, separatory is got organic phase, and is stand-by behind the anhydrous magnesium sulfate drying.
C. take by weighing the mixture 5g that processed according to above-mentioned steps b, add 100g alkali alumina and 250ml normal heptane, 90 ℃ of lower altogether thermal response 8h that reflux cross leaching filtrate, vacuum distilling filtrate.Repeat this step until the filtrate clarification.Recrystallization in the low temperature bath, yield 60.3%, purity 60.2%.
Embodiment 6
A. take by weighing respectively p-ten.-butylcatechol 8.3g (0.05mol) and cesium carbonate 36.1g (0.111mol) is dissolved in the 200ml acetonitrile, wherein cesium carbonate at twice equivalent add.Take by weighing a certain amount of glycol ether xylene sulfonate at twice equivalent be dissolved in the 100ml acetonitrile, place constant pressure funnel to drip.60 ℃ of lower reaction 24h, reaction conversion ratio 31.2%.
B. will filter according to the mixture that above-mentioned steps a obtains, get filtrate vacuum distilling.Methyl alcohol stripping raffinate continues to filter, and gets filtrate vacuum distilling again.Methylene dichloride stripping raffinate, with the sodium thiosulfate solution repetitive scrubbing of 1N HCl and heat, separatory is got organic phase, and is stand-by behind the anhydrous magnesium sulfate drying.
C. take by weighing 200-300 purpose column chromatography silica gel 30g, dry column-packing.Take by weighing the mixture 1g that processed according to above-mentioned steps b as the sample loading.Select first and consist of sherwood oil: ethyl acetate: the eluent of methylene dichloride=1: 1: 0.2 carries out wash-out; Select and consist of sherwood oil: acetone: the eluent of methylene dichloride=1: 1: 0.1 carries out wash-out; Select at last and consist of sherwood oil: methyl alcohol: the eluent of methylene dichloride=1: 0.2: 0.2 carries out wash-out.Repeat this gradient elution, until wash out contained all 4 ' 4 in the mixture " (5 ")-di-t-butyl dibenzo-18-hat-6.Collection is dissolved with the elutant of purpose product, and vacuum distilling is with pouring in the normal heptane that boils the temperature programmed control recrystallization behind the methylene dichloride stripping raffinate into.Yield 25.2%, purity 71.4%.
Comparative example 1
Utilize the alkylated reaction of phenyl ring prepare 4 ', 4 " (5 ")-di-t-butyl dibenzo-18-hat-6.Take dibenzo-18-hat-6 and the trimethyl carbinol as reactant, trifluoroacetic acid is solvent, 70 ℃ of lower reaction 24h, reaction conversion ratio 15.9%.
Comparative example 2
Take p-ten.-butylcatechol and glycol ether xylene sulfonate as reactant, replace template cesium carbonate in the embodiment of the invention 1 with salt of wormwood, take tetrahydrofuran (THF) as solvent, carry out building-up reactions according to the step a in the embodiments of the invention 1, reaction conversion ratio 17.8%.
Comparative example 3
Carry out building-up reactions according to the step a in the embodiments of the invention 1, adopt the purification process of Separation by Complexation to carry out separation and purification, 4 ', 4 " (5 ")-di-t-butyl dibenzo-18-hat-6 yields are 13.4%, purity is 35.6%.
Comparative example 4
Carry out building-up reactions according to the step a in the embodiment of the invention 1, the purification process such as employing is simply filtered, precipitation, recrystallization carry out separation and purification, 4 ', 4 " (5 ")-di-t-butyl dibenzo-18-hat-6 yields are 9.7%, purity is 23.3%.
By above result as can be known, prove that the embodiment 1,2,3,4,5 of validity of the present invention, 6 reaction conversion ratio are respectively: 52.3%, 43.8%, 33.7%, 37.6%, 35.2%, 31.2%; And comparative example 1,2 reaction conversion ratio are respectively: 15.9%, 17.8%.Be not difficult to find out that synthetic route of the present invention significantly improves reaction conversion ratio.
Simultaneously, illustrate that the embodiment 1,2,3,4,5 of separating effect of the present invention, the yield of 6 purpose product are respectively: 53.1%, 18.3%, 22.1%, 66.4%, 60.3%, 25.2%, purity is respectively: 65.9%, 85.7%, 77.5%, 53.6%, 60.2%, 71.4%.Contrast with comparative example 5,6 that (product yield is 13.4%, 9.7%, product purity is 35.6%, 23.3%), can find out separation purifying technique of the present invention greatly improved 4 ', 4 " (5 ")-yield and the purity of di-t-butyl dibenzo-18-hat-6.
Claims (2)
1. one kind 4 ' 4 " preparation technology of (5 ")-di-t-butyl dibenzo-18-hat-6; it is characterized in that; selecting p-ten.-butylcatechol and glycol ether two p-toluenesulfonic esters is raw material; selecting cesium carbonate is template; selecting tetrahydrofuran (THF) is solvent; the initial volumetric molar concentration of p-ten.-butylcatechol is 0.1-0.25mol/l; the mol ratio of p-ten.-butylcatechol and cesium carbonate is 1:2.2-3; above reaction mass is added in the reactor; and protect with nitrogen atmosphere; 40 ℃-80 ℃ lower synthetic obtains containing purpose products 4 ' 4 " mixture of (5 ")-di-t-butyl dibenzo-18-hat-6, reaction formula is as follows:
After reaction finishes, the configuration eluent, carry out the column chromatography gradient elution and come the separation and purification mixture, obtain at last purifying 4 ' 4 " (5 ")-di-t-butyl dibenzo-18-hat-6, wherein, the column chromatography gradient elution is three times, and according to volume ratio, primary eluent consists of sherwood oil: ethyl acetate: methylene dichloride=1:0.8-1.2:0.1-0.3; Secondary eluent consists of sherwood oil: acetone: methylene dichloride=1:0.5-1.2:0.05-0.2; Eluent for the third time consists of sherwood oil: methyl alcohol: methylene dichloride=1:0.1-0.3:0.1-0.3.
2. the preparation technology of as claimed in claim 14 ' 4 " (5 ")-di-t-butyl dibenzo-18-hat-6 is characterized in that the mass ratio of mixture and post layer silica gel is 1:30-100 in the column chromatography gradient elution.
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| Charles J. Pedersen.Cyclic polyethers and their complexes with metal salts.《J. Am. Chem. Soc.》.1967,第89卷(第26期),7017–7036. * |
| HUANG, Zhi-Bin, et al.Synthesis and Optical Properties of 2,13-Dibenzothiazol-2’-yldibenzo[b,k]-18-crown-6.《Chinese Journal of Chemistry》.2008,第26卷(第6期),1096-1100. * |
| Richard A. Sachleben, et al.Synthesis and Structures of Isomerically Pure Bis-(Alkylbenzo) Crown Ethers.《Tetrahedron》.1997,第53卷(第40期),13567-13582. * |
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