CN103351396A - Preparation method of 4, 4-dimethyl-3, 5, 8-trioxabicyclo [5, 1, 0] octane - Google Patents
Preparation method of 4, 4-dimethyl-3, 5, 8-trioxabicyclo [5, 1, 0] octane Download PDFInfo
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- CN103351396A CN103351396A CN2013103223011A CN201310322301A CN103351396A CN 103351396 A CN103351396 A CN 103351396A CN 2013103223011 A CN2013103223011 A CN 2013103223011A CN 201310322301 A CN201310322301 A CN 201310322301A CN 103351396 A CN103351396 A CN 103351396A
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- alkene
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- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- GEKNCWQQNMEIMS-UHFFFAOYSA-N 4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]octane Chemical compound C1OC(C)(C)OCC2OC21 GEKNCWQQNMEIMS-UHFFFAOYSA-N 0.000 title abstract description 4
- 238000006243 chemical reaction Methods 0.000 claims abstract description 25
- HEWZVZIVELJPQZ-UHFFFAOYSA-N 2,2-dimethoxypropane Chemical compound COC(C)(C)OC HEWZVZIVELJPQZ-UHFFFAOYSA-N 0.000 claims abstract description 8
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000002994 raw material Substances 0.000 claims abstract description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims abstract description 5
- 238000007363 ring formation reaction Methods 0.000 claims abstract description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 27
- 239000012043 crude product Substances 0.000 claims description 11
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 9
- 238000003756 stirring Methods 0.000 claims description 9
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 claims description 8
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 claims description 7
- 239000000047 product Substances 0.000 claims description 7
- 239000007864 aqueous solution Substances 0.000 claims description 6
- 239000000706 filtrate Substances 0.000 claims description 6
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 claims description 6
- 238000005406 washing Methods 0.000 claims description 6
- 238000004821 distillation Methods 0.000 claims description 5
- 239000000243 solution Substances 0.000 claims description 5
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 3
- 239000006227 byproduct Substances 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 235000010265 sodium sulphite Nutrition 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 238000010025 steaming Methods 0.000 claims description 3
- 238000004807 desolvation Methods 0.000 claims description 2
- 238000002386 leaching Methods 0.000 claims description 2
- 239000000376 reactant Substances 0.000 claims description 2
- 239000003054 catalyst Substances 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 5
- ORTVZLZNOYNASJ-UPHRSURJSA-N (z)-but-2-ene-1,4-diol Chemical compound OC\C=C/CO ORTVZLZNOYNASJ-UPHRSURJSA-N 0.000 abstract 1
- KYEJVSYUPWCUOL-UHFFFAOYSA-N CC1(OCP2OC2CO1)C Chemical compound CC1(OCP2OC2CO1)C KYEJVSYUPWCUOL-UHFFFAOYSA-N 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 230000003068 static effect Effects 0.000 description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- -1 distillation: 80g Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000003317 industrial substance Substances 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
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- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention relates to a preparation method of 4, 4-dimethyl-3, 5, 8-trioxabicyclo [5, 1, 0] octane. The preparation method comprises the following steps: (1), performing cyclization reaction on 2-butene-1, 4-diol and 2, 2-dimethoxypropane in the presence of concentrated sulfuric acid to obtain 4, 7-dihydro-2, 2-dimethyl-1, 3-dioxepan-5-ene; (2), performing reaction on 4, 7-dihydro-2, 2-dimethyl-1, 3-dioxepan-5-ene obtained in step (1) meta-chloroperoxybenzoic acid to obtain the 4, 4-dimethyl-3, 5, 8-trioxabicyclo [5, 1, 0] octane. According to the method, the reaction yield in the step (1) can reach 85 percent, the yield in the step (2) can reach 60 percent, and the total yield can reach 50 percent, and the purity of the obtained product is greater than 98 percent. In addition, in the method, raw materials are easy to get, and the operation is convenient.
Description
Technical field
The present invention relates to a kind of 4,4-dimethyl-3,5, the preparation method of 8-trioxa-l-phosphabicyclo [5,1,0] octane.
Background technology
4,4-dimethyl-3,5,8-trioxa-l-phosphabicyclo [5,1,0] octane, CAS number: 57280-22-5, molecular formula: C
7H
12O
3, structural formula is as follows:
4,4-dimethyl-3,5,8-trioxa-l-phosphabicyclo [5,1,0] octane is the very large industrial chemicals of consumption, the commercially available prod is expensive.So far, yet there are no about the Patents of this product synthetic method report.
Summary of the invention
Technical problem to be solved by this invention is to overcome to provide a kind of 4,4-dimethyl-3,5, and the preparation method of 8-trioxa-l-phosphabicyclo [5,1,0] octane, the method is simple to operate, and yield is high, and cost is low.
For solving above technical problem, the present invention takes following technical scheme:
A kind of 4,4-dimethyl-3,5, the preparation method of 8-trioxa-l-phosphabicyclo [5,1,0] octane, it comprises the steps:
(1), makes 2-butylene-Isosorbide-5-Nitrae-glycol and 2,2-dimethoxypropane that ring-closure reaction occur to generate 4,7-dihydro-2 2-dimethyl-1,3-dioxane heptan-5-alkene in the presence of the catalyzer vitriol oil;
(2), make step (1) gained 4,7-dihydro-2,2-dimethyl-1, it is described 4 that 3-dioxane heptan-5-alkene and metachloroperbenzoic acid reaction generate, 4-dimethyl-3,5,8-trioxa-l-phosphabicyclo [5,1,0] octane.
Further, in the step (1), the molar ratio of 2-butylene-Isosorbide-5-Nitrae-glycol and 2,2-dimethoxypropane is preferably 1:1.98～2.05, more preferably 1:2.
In the step (1), the adding quality optimization of catalyzer is 0.05%～0.2% of 2-butylene-Isosorbide-5-Nitrae-glycol quality.
In the step (1), described reaction is carried out under temperature 50 C～70 ℃.
In the step (1), the concentration of the vitriol oil is preferably 95wt%～98wt%.
According to a concrete aspect of the present invention, step (1) implementation is as follows: add successively 2,2-dimethoxypropane in the reactor that stirring and condenser are housed, 2-butylene-1,4-two pure and mild catalyzer, after unlatching is stirred to reactant and is tied to form homogeneous phase, begin to heat up, when reactor temperature reaches 70 ℃, when reactor top temperature is 60 ℃, begin to steam by-product carbinol, until there is not methyl alcohol to steam, temperature in the kettle begins to raise, when still top temperature begins to descend, finish reaction, be cooled to 50 ℃, underpressure distillation, remove residual methanol, to steaming without methyl alcohol, finish changing receiving vessel, the resistates in the reactor is carried out underpressure distillation, obtain 4,7-dihydro-2,2-dimethyl-1, the crude product of 3-dioxane heptan-5-alkene, this crude product is through rectifying, obtain 4,7-dihydro-2,2-dimethyl-1, the elaboration of 3-dioxane heptan-5-alkene is used for next step reaction.
Further, in the step (2), described reaction is carried out in the solvent ethylene dichloride.
Preferably, in the step (2), described reaction is at room temperature carried out.
Preferably, in the step (2), 4,7-dihydro-2,2-dimethyl-1, the molar ratio of 3-dioxane heptan-5-alkene and metachloroperbenzoic acid is 1:0.95～1.05.
According to another concrete aspect of the present invention, step (2) implementation is as follows: with step (1) gained 4,7-dihydro-2,2-dimethyl-1,3-dioxane heptan-5-alkene obtains 4,7-dihydro-2,2-dimethyl-1 with the methylene dichloride dissolving, the solution of 3-dioxane heptan-5-alkene adds in the dropping funnel for subsequent use; In reactor, add ethylene dichloride, stir the lower metachloroperbenzoic acid that adds, finish, drip 4,7-dihydro-2 under the room temperature, 2-dimethyl-1, the solution of 3-dioxane heptan-5-alkene finishes, and continues room temperature reaction till can't detect raw material, continue reaction 1～2 hour, finish reaction, filter, use the ethylene dichloride washing leaching cake, be filtered dry, get filtrate, filtrate through 10% sodium sulfite aqueous solution, saturated sodium bicarbonate aqueous solution washing and anhydrous sodium sulfate drying, is filtered successively, desolvation gets crude product, distills to get finished product.
Synthetic route of the present invention is expressed as follows with chemical equation:
Because the enforcement of above technical scheme, the present invention compared with prior art has following advantage:
Can reach 85% according to the inventive method the first step reaction yield, the second step yield can reach more than 60%, and overall yield of reaction can reach more than 50%, and products obtained therefrom purity is greater than 98%.In addition, raw material of the present invention is easy to get, and is easy to operate.
Embodiment
The present invention will be further described in detail below in conjunction with specific embodiment.
A kind of 4,4-dimethyl-3,5, the preparation method of 8-trioxa-l-phosphabicyclo [5,1,0] octane (calling DOT in the following text), it comprises the steps:
(1) ring-closure reaction: in the 500ml flask, successively add 2,2-dimethoxypropane 208g, 2-butylene-1,4-glycol 88g, and catalyzer (98wt% sulfuric acid) 0.1g, unlatching begins to heat up after stirring and becoming homogeneous phase in 10 minutes, treat that the Fu temperature reaches 70 ℃, when pushing up warm 60 ℃, begin to steam by-product carbinol.Until steam to the greatest extent, the still temperature rise, the top temperature finishes when descending.Then cooling when treating that the still temperature is got back to 50 ℃, under the little band of vacuum, is removed residual methanol.Finish changing receiving bottle, negative pressure is steamed the first step product crude product, 60 ℃ of Fu temperature, and 58 ℃ of beginnings of top temperature dischargings, rear top temperature keeps 61 ℃ substantially, until steaming is most, gets 4,7-dihydro-2,2-dimethyl-1,3-dioxane heptan-5-alkene crude product is 118g approximately.With 4,7-dihydro-2,2-dimethyl-1,3-dioxane heptan-5-alkene crude product carries out rectifying, obtains 4,7-dihydro-2,2-dimethyl-1,3-dioxane heptan-5-alkene elaboration 110g.Yield: 85%.
(2) oxidizing reaction: the 500ml flask adds ethylene dichloride 300ml and step (1) gained 4,7-dihydro-2, and 2-dimethyl-1, in 3-dioxane heptan-5-alkene elaboration 100, the rear adding addition funnel that stirs is for subsequent use.Add ethylene dichloride 1000ml under the 2000ml flask room temperature, stir lower adding metachloroperbenzoic acid 134.8g, drip 4 under the room temperature, 7-dihydro-2,2-dimethyl-1, the dichloroethane solution of 3-dioxane heptan-5-alkene elaboration, time 2 h, then continue under the room temperature reaction 15-20 hour, the some plate without raw material after, continue reaction and finish after 2 hours, filter, with ethylene dichloride rinsing filter cake, be filtered dry, get filtrate.
The filtrate aftertreatment: 10% sodium sulfite aqueous solution 1000ml at first, stir that 10min is static, layering washing extracted organic phase; Then add saturated sodium bicarbonate aqueous solution 1500ml, stir 30min, static, layering, the washing extracted organic phase is through anhydrous sodium sulfate drying, filter, precipitation, negative pressure boils off solvent, gets approximately 80g of crude product, distillation: 80g, crude product steam approximately 70g product, are DOT, yield: 62%.The density 1.071g/cm of product
3, 179 ℃ of fusing points, flash-point 56%, HPLC content 98.2%.
Above-described embodiment only is explanation technical conceive of the present invention and characteristics; its purpose is to allow the personage who is familiar with technique can understand content of the present invention and according to this enforcement; can not limit protection scope of the present invention with this; all equivalences that spirit is done according to the present invention change or modify, and all should be encompassed within protection scope of the present invention.
Claims (10)
1. one kind 4,4-dimethyl-3,5, the preparation method of 8-trioxa-l-phosphabicyclo [5,1,0] octane is characterized in that: comprise the steps:
(1), makes 2-butylene-Isosorbide-5-Nitrae-glycol and 2,2-dimethoxypropane that ring-closure reaction occur to generate 4,7-dihydro-2 2-dimethyl-1,3-dioxane heptan-5-alkene in the presence of the catalyzer vitriol oil;
(2), make step (1) gained 4,7-dihydro-2,2-dimethyl-1, it is described 4 that 3-dioxane heptan-5-alkene and metachloroperbenzoic acid reaction generate, 4-dimethyl-3,5,8-trioxa-l-phosphabicyclo [5,1,0] octane.
2. preparation method according to claim 1, it is characterized in that: in the step (1), the molar ratio of 2-butylene-Isosorbide-5-Nitrae-glycol and 2,2-dimethoxypropane is 1:1.98 ~ 2.05.
3. preparation method according to claim 1, it is characterized in that: in the step (1), the adding quality of catalyst sulfuric acid is 0.05% ~ 0.2% of 2-butylene-Isosorbide-5-Nitrae-glycol quality.
4. preparation method according to claim 1 is characterized in that: in the step (1), described reaction is carried out under temperature 50 C ~ 70 ℃.
5. preparation method according to claim 1, it is characterized in that: in the step (1), the concentration of the described vitriol oil is 95wt% ~ 98wt%.
6. the described preparation method of each claim in 5 according to claim 1, it is characterized in that: step (1) implementation is as follows: to be equipped with stir and the reactor of condenser in add successively 2,2-dimethoxypropane, 2-butylene-1,4-two pure and mild catalyzer, after unlatching is stirred to reactant and is tied to form homogeneous phase, begin to heat up, when reactor temperature reaches 70 ℃, when reactor top temperature is 60 ℃, begin to steam by-product carbinol, until there is not methyl alcohol to steam, temperature in the kettle begins to raise, when still top temperature begins to descend, finish reaction, be cooled to 50 ℃, underpressure distillation, remove residual methanol, to steaming without methyl alcohol, finish changing receiving vessel, the resistates in the reactor is carried out underpressure distillation, obtain 4,7-dihydro-2,2-dimethyl-1, the crude product of 3-dioxane heptan-5-alkene, this crude product is through rectifying, obtain 4,7-dihydro-2,2-dimethyl-1, the elaboration of 3-dioxane heptan-5-alkene is used for next step reaction.
7. preparation method according to claim 1 is characterized in that: in the step (2), described reaction is carried out in the solvent ethylene dichloride.
8. preparation method according to claim 1 is characterized in that: in the step (2), described reaction is at room temperature carried out.
9. preparation method according to claim 1 is characterized in that: in the step (2), and 4,7-dihydro-2,2-dimethyl-1, the molar ratio of 3-dioxane heptan-5-alkene and metachloroperbenzoic acid is 1:0.95 ~ 1.05.
10. according to claim 1,7,8 or 9 described preparation methods, it is characterized in that: step (2) implementation is as follows: with step (1) gained 4,7-dihydro-2,2-dimethyl-1,3-dioxane heptan-5-alkene obtains 4,7-dihydro-2,2-dimethyl-1 with the methylene dichloride dissolving, the solution of 3-dioxane heptan-5-alkene adds in the dropping funnel for subsequent use; In reactor, add ethylene dichloride, stir the lower metachloroperbenzoic acid that adds, finish, drip 4,7-dihydro-2 under the room temperature, 2-dimethyl-1, the solution of 3-dioxane heptan-5-alkene finishes, and continues room temperature reaction till can't detect raw material, continue reaction 1 ~ 2 hour, finish reaction, filter, use the ethylene dichloride washing leaching cake, be filtered dry, get filtrate, filtrate through 10% sodium sulfite aqueous solution, saturated sodium bicarbonate aqueous solution washing and anhydrous sodium sulfate drying, is filtered successively, desolvation gets crude product, distills to get finished product.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106967083A (en) * | 2017-04-26 | 2017-07-21 | 穆云 | The process of preparing of Gadobutrol epoxy side chain intermediate |
| CN109251209A (en) * | 2018-10-23 | 2019-01-22 | 湖北天舒药业有限公司 | A kind of preparation process of Gadobutrol intermediate |
| CN115724849A (en) * | 2022-11-28 | 2023-03-03 | 安庆朗坤药业有限公司 | A kind of preparation method of 4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]octane |
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| US4439613A (en) * | 1980-04-17 | 1984-03-27 | The Regents Of The University Of California | Novel amino-dioxepane intermediates for the synthesis of new non-ionic contrast media |
| CN102964212A (en) * | 2012-11-15 | 2013-03-13 | 大连九信生物化工科技有限公司 | A kind of synthetic method of 1,2,4-butanetriol |
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2013
- 2013-07-29 CN CN2013103223011A patent/CN103351396A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4439613A (en) * | 1980-04-17 | 1984-03-27 | The Regents Of The University Of California | Novel amino-dioxepane intermediates for the synthesis of new non-ionic contrast media |
| CN102964212A (en) * | 2012-11-15 | 2013-03-13 | 大连九信生物化工科技有限公司 | A kind of synthetic method of 1,2,4-butanetriol |
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| Title |
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| M.MISCHITZ ET AL: "Asymmetric Microbial Hydrolysis of Epoxides", 《TETRAHEDRON ASYMMETRY》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106967083A (en) * | 2017-04-26 | 2017-07-21 | 穆云 | The process of preparing of Gadobutrol epoxy side chain intermediate |
| CN106967083B (en) * | 2017-04-26 | 2020-09-15 | 穆云 | Preparation process method of gadobutrol epoxy side chain intermediate |
| CN109251209A (en) * | 2018-10-23 | 2019-01-22 | 湖北天舒药业有限公司 | A kind of preparation process of Gadobutrol intermediate |
| CN115724849A (en) * | 2022-11-28 | 2023-03-03 | 安庆朗坤药业有限公司 | A kind of preparation method of 4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]octane |
| CN115724849B (en) * | 2022-11-28 | 2025-01-24 | 安庆朗坤药业有限公司 | A preparation method of 4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]octane |
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Application publication date: 20131016 |