CN103333057A - Method for preparing DHBE (dihydroxy dibutyl ether) - Google Patents
Method for preparing DHBE (dihydroxy dibutyl ether) Download PDFInfo
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- CN103333057A CN103333057A CN2013102517836A CN201310251783A CN103333057A CN 103333057 A CN103333057 A CN 103333057A CN 2013102517836 A CN2013102517836 A CN 2013102517836A CN 201310251783 A CN201310251783 A CN 201310251783A CN 103333057 A CN103333057 A CN 103333057A
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- dihydroxydibutylether
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Abstract
The invention relates to the field of chemical material preparation and discloses an efficient and simple method for preparing DHBE (dihydroxy dibutyl ether) for drug use. The method comprises the following steps of catalyzing 1,3-butanediol with a solid superacid catalyst with mass percentage of 1.0%-50% or a hydrogen molecular sieve based catalyst at 50-190 DEG C so as to prepare the dihydroxy dibutyl ether through condensation, after reaction, cooling and filtering the product, and obtaining the dihydroxy dibutyl ether with content more than or equal to 95 percent through reduced pressure distillation of the product. The dihydroxy dibutyl ether is suitable for being used as bulk drug of cholagogue Dyskinebul, and the method is environment-friendly and efficient, has low cost, is simple to operate, and is suitable for large-scale industrial production.
Description
Technical field
The invention belongs to the industrial chemicals preparation field, refer in particular to the environment-friendly preparation method thereof of dihydroxydibutylether.This product can be used as the bulk drug of the auxiliary usefulness of liver and gall diseases.
Background technology
(dihudroxudibutylether is the flaxen oily liquids of a kind of no color or smell DHBE) to dihydroxydibutylether, is widely used in field of fine chemical such as medicine, industrial detergent and dispersion agent.Especially at field of medicaments, dihydroxydibutylether (DHBE) capsule is used as the marketization for the treatment of liver and gall diseases medicine and goes on the market in a plurality of countries.Commodity are called Dyskinebyl (Dyskinebul), are at first succeeded in developing and are put on market by French Laphal pharmaceutical factory.This medicine belongs to the two-way promotor of choleresis, and have cholagogic, anti-inflammatory, spasmolysis, protect courage, arrange masonry usefulness, be a kind of choleretic efficiently.
Dihydroxydibutylether is isomer mixture, it mainly contains 3 isomer: 4-(3-hydroxyl butoxy)-and 2-butanols (I), 3-(3-hydroxyl butoxy)-1-butanols (II) and 3-(3-hydroxyl-1-methyl propoxy-)-1-butanols (III) (Hayashi T, ChemPhanmBull, 1981,29 (11): 3158-3172) form.Structural formula is as follows:
（Ⅰ）
4-(3-hydroxyl butoxy)-2-butanols (I)
（Ⅱ）
3-(3-hydroxyl butoxy)-1-butanols (II)
（Ⅲ）
3-(3-hydroxyl-1-methyl propoxy-)-1-butanols (III)
Elso Manghisi at United States Patent (USP) (1986) US4584321 to 1, the dehydrating step of 3-butyleneglycol is studied, the sulphuric acid catalysis reaction process is narrated, sulphuric acid catalysis 1, the intermolecular dehydrating condensation of 3-butyleneglycol becomes ether, obtaining dihydroxydibutylether, yield 18.9% through underpressure distillation separation purification.Synthetic route is as follows:
The sulfuric acid catalysis legal system is equipped with dihydroxydibutylether
Fig.1?Method?of?DHBE?synthesize?by?sulfuric?acid
Felisati D (FR 1267084A) has developed another synthetic route of 3,3-dihydroxydibutylether.In this route 2,2 '-dicyano ether and the reaction of monobromethane Grignard reagent, hydrolysis gets 3 again, 3 '-dioxo dibutyl ether, hydrogenation obtains dihydroxydibutylether again, yield 15%.Synthetic route is as follows:
Monobromethane Grignard reagent reaction method
Fig.2?Method?of?methyl?bromide?grignard?reagent?reaction
Dihydroxydibutylether mainly still adopts sulfuric acid catalyst at present in Industrial processes, though its technology is ripe, but in later stage separation and processing purifying technique, environmental pressure is big, and have an inevitable shortcoming, as catalyzer difficult recovery, corrosive equipment, be difficult to that continuous production, yield are low, water and power consumption reach sulfuric acid waste greatly and handle problems such as difficulty.It is little to be badly in need of the development environment burden under this situation, the technology of green preparation dihydroxydibutylether.
Summary of the invention
Purpose of the present invention is developed a kind of heterogeneous catalytic system catalysis 1,3 butylene glycol condensation prepared dihydroxydibutylether, and catalyzer easily separates with thing with reactant, etching apparatus not.Make simultaneously production process have aftertreatment simply, characteristics such as contaminate environment seldom.Heterogeneous catalyst of the present invention is is a kind of solid super-strong acid.
Technical scheme of the present invention is as follows:
A kind of preparation method of dihydroxydibutylether, with mass percent be 1.0～50% solid super-strong acid or molecular sieve as catalyzer, catalysis 1,3 butylene glycol condensation prepared dihydroxydibutylether in 10 hours under 50～190 ℃ of temperature; With dihydroxydibutylether cooling, filtration, the underpressure distillation that obtains, obtain the dihydroxydibutylether of content 〉=97%.
Described solid super-strong acid is a kind of or its mixing in SO42-/MxOy type solid super-strong acid, the compound metal oxide solid super acid, and described molecular sieve can be chosen as hydrogen type molecular sieve; The described reaction times can be 0.3～4 hour, and reaction pressure is controlled at 0.04-0.1MPa.
The present invention compares with existing dihydroxydibutylether production technique, has the following advantages:
(1) catalyst system therefor is solid acid catalyst, can reclaim and recycle;
(2) compare with traditional technology, technology aftertreatment of the present invention is simple, and reaction product only needs a step underpressure distillation purification process to obtain, and purity is greater than 97.5%.
(3) present method adopts that economy is easy to get, separates with liquid-phase reaction system easily, the solid acid of etching apparatus not, and relative more environmental protection of sulfuric acid meets the theory of Green Chemistry.Be fit to large-scale production and production continuously, guarantee quality product, production cost is low simultaneously.
Embodiment
Embodiment one
Measure 150.0g(0.83mol) 1,3 butylene glycol join in the 250ml there-necked flask of being furnished with thermometer of good seal, together add 1% compound metal oxide solid super acid, stir, the oil bath heating, rise to 185～190 ℃ of temperature of reaction after, reacted transformation efficiency 57% 4 hours.After treating that product is cooled to room temperature, the solids removed by filtration super acidic catalyst, (114～124 ℃/5mm Hg) obtains dihydroxydibutylether with the product underpressure distillation.Measure through GC, product content is 96.1%.
Embodiment two
Measure 150.0g(0.83mol) 1,3 butylene glycol add in the there-necked flask, together add 5% compound metal oxide solid super acid, stir, the oil bath heating, rise to 115～152 ℃ of temperature of reaction after, reacted transformation efficiency 82% 1.5 hours.After treating that product is cooled to room temperature, (114～124 ℃/5mm Hg) obtains dihydroxydibutylether with the product underpressure distillation.Measure product content 97.8% through GC.
Embodiment three
Measure 150.0g(0.83mol) 1,3 butylene glycol add in the there-necked flask, together add 15% compound metal oxide solid super acid, stir, the oil bath heating, rise to 117～148 ℃ of temperature of reaction after, reacted transformation efficiency 80% 1 hour.After treating that product is cooled to room temperature, the product underpressure distillation is obtained the dihydroxydibutylether product.Measure product content 95.3% through GC.
Embodiment four
The acid of use compound metal oxide solid super, other method such as embodiment one, 50 ℃ of temperature of reaction, catalyst levels 50%, 0.3 hour reaction times, transformation efficiency 19%.The cooling of reaction back is filtered, and underpressure distillation obtains the dihydroxydibutylether product.Measure through GC, product content is 97.2%.
Embodiment five
The acid of use compound metal oxide solid super, catalyst levels 5%, with 150.0g(0.83mol) 1,3-butyleneglycol and catalyzer together join in the 250ml there-necked flask of the good seal that is connected to prolong, and the oil bath heating is also stirred, and (reacts under 0.04～0.05MPa) in decompression, lower-boiling impurity in the reaction process inserts round-bottomed flask through prolong, 120～148 ℃ of temperature of reaction, 1.5 hours reaction times, transformation efficiency 84%.The cooling of reaction back is filtered, and underpressure distillation (114～124 ℃/5mm Hg) obtains the dihydroxydibutylether product.Product content is 98.3%.
Embodiment six
The acid of use compound metal oxide solid super, catalyst levels 5%, with 1 of 200g, 3-butyleneglycol and catalyzer together join in the 500ml there-necked flask that is connected to the prolong good seal, and the oil bath heating is also stirred, and reacts under decompression (0.04mpa), lower-boiling impurity in the reaction process is linked into round-bottomed flask through prolong, 120～145 ℃ of temperature of reaction were reacted transformation efficiency 68% 1 hour.The cooling of reaction back is filtered, and underpressure distillation (114～124 ℃/5mm Hg) obtains dihydroxydibutylether.Measure through GC, product content is 97.9%.
Embodiment seven
Use SO
4 2-/ M
xO
yThe type solid super-strong acid, catalyst levels 8% joins the 1,3 butylene glycol of 150g in the 250ml there-necked flask, and other is with method six, and 125～134 ℃ of temperature of reaction were reacted transformation efficiency 51% 1 hour.The cooling of reaction back is filtered, and underpressure distillation (114～124 ℃/5mm Hg) obtains the dihydroxydibutylether product.Measure through GC, product content is 98.2%.
Embodiment eight
Use the hydrogen type molecular sieve catalyzer, catalyst levels 8% joins the analytically pure 1,3 butylene glycol of 150g in the 250ml there-necked flask, and other is with method six, and 164～178 ℃ of temperature of reaction were reacted transformation efficiency 55% 1 hour.The cooling of reaction back is filtered, and underpressure distillation (114～124 ℃/5mm Hg) obtains dihydroxydibutylether.Measure through GC, product content is 98.0%.
Embodiment nine
Use the hydrogen type molecular sieve catalyzer, catalyst levels 5%, with 1 of 200g, 3-butyleneglycol and catalyzer together join in the 500ml there-necked flask that is connected to the prolong good seal, and the oil bath heating is also stirred, and reacts under decompression (0.04mpa), lower-boiling impurity in the reaction process is linked into round-bottomed flask through prolong, 150～175 ℃ of temperature of reaction were reacted transformation efficiency 68% 2 hours.The cooling of reaction back is filtered, and underpressure distillation (114～124 ℃/5mm Hg) obtains dihydroxydibutylether.Measure through GC, product content is 98.8%.
Embodiment ten
Use the hydrogen type molecular sieve catalyzer, catalyst levels 35%, with 1 of 200g, 3-butyleneglycol and catalyzer together join in the 500ml there-necked flask that is connected to the prolong good seal, and the oil bath heating is also stirred, and reacts under decompression (0.04mpa), lower-boiling impurity in the reaction process is linked into round-bottomed flask through prolong, 185～190 ℃ of temperature of reaction were reacted transformation efficiency 32% 0.3 hour.The cooling of reaction back is filtered, and underpressure distillation (114～124 ℃/5mm Hg) obtains dihydroxydibutylether, measures through GC, and product content is 98.4%.
Embodiment 11
Use SO
4 2-/ M
xO
yType solid super-strong acid and compound metal oxide solid super acid are added for the 1:5 ratio according to mass ratio, and catalyst levels is 8%, with 150g analytically pure 1, the 3-butyleneglycol joins in the 250ml there-necked flask, and other is with embodiment six, 124～138 ℃ of temperature of reaction, reacted transformation efficiency 59% 1 hour.The cooling of reaction back is filtered, and underpressure distillation (114～124 ℃/5mm Hg) obtains dihydroxydibutylether.Measure through GC, product content is 98.0%.
Claims (8)
1. the preparation method of a dihydroxydibutylether is characterized in that, with mass percent be 1.0～50% solid super-strong acid or molecular sieve as catalyzer, catalysis 1,3 butylene glycol condensation prepared dihydroxydibutylether in 10 hours under 50～190 ℃ of temperature; With dihydroxydibutylether cooling, filtration, the underpressure distillation that obtains, obtain the dihydroxydibutylether of content 〉=95%.
2. preparation method according to claim 1 is characterized in that, described solid super-strong acid is SO
4 2-/ M
xO
yA kind of or its mixing in type solid super-strong acid, the compound metal oxide solid super acid.
3. preparation method according to claim 1 and 2 is characterized in that, described molecular sieve is hydrogen type molecular sieve.
4. preparation method according to claim 1 and 2 is characterized in that, 0.3～4 hour described reaction times.
5. preparation method according to claim 3 is characterized in that, 0.3～4 hour described reaction times.
6. according to claim 1,2 or 5 described preparation methods, it is characterized in that described reaction pressure is 0.04-0.1MPa.
7. preparation method according to claim 3 is characterized in that, described reaction pressure is 0.04-0.1MPa.
8. preparation method according to claim 4 is characterized in that, described reaction pressure is 0.04-0.1MPa.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4584321A (en) * | 1983-05-30 | 1986-04-22 | Istituto Luso Farmaco D'italia S.P.A. | 3-(3-Hydroxybutoxy)-1-butanol in pharmaceutical compositions |
| CN101559361A (en) * | 2009-05-18 | 2009-10-21 | 天津工业大学 | Mg/Al/X ternary composite metal oxide catalyst and preparation method thereof |
| CN101624334A (en) * | 2008-07-11 | 2010-01-13 | 中国科学院大连化学物理研究所 | Method for preparing glycerin ether from glycerol |
| CN102924241A (en) * | 2012-10-26 | 2013-02-13 | 浙江新化化工股份有限公司 | Diisopropyl ether production method |
-
2013
- 2013-06-24 CN CN2013102517836A patent/CN103333057A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4584321A (en) * | 1983-05-30 | 1986-04-22 | Istituto Luso Farmaco D'italia S.P.A. | 3-(3-Hydroxybutoxy)-1-butanol in pharmaceutical compositions |
| CN101624334A (en) * | 2008-07-11 | 2010-01-13 | 中国科学院大连化学物理研究所 | Method for preparing glycerin ether from glycerol |
| CN101559361A (en) * | 2009-05-18 | 2009-10-21 | 天津工业大学 | Mg/Al/X ternary composite metal oxide catalyst and preparation method thereof |
| CN102924241A (en) * | 2012-10-26 | 2013-02-13 | 浙江新化化工股份有限公司 | Diisopropyl ether production method |
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Application publication date: 20131002 |