CN103896903A - Method for preparing and purifying 2,3-O-isopropylidene threitol - Google Patents
Method for preparing and purifying 2,3-O-isopropylidene threitol Download PDFInfo
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- CN103896903A CN103896903A CN201310705598.XA CN201310705598A CN103896903A CN 103896903 A CN103896903 A CN 103896903A CN 201310705598 A CN201310705598 A CN 201310705598A CN 103896903 A CN103896903 A CN 103896903A
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- threitol
- ethanol
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- isopropoxy
- isopropylidene
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
- C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D317/18—Radicals substituted by singly bound oxygen or sulfur atoms
- C07D317/20—Free hydroxyl or mercaptan
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Abstract
The invention discloses a method for preparing and purifying 2,3-O-isopropylidene threitol. The preparation method comprises the following steps of uniformly mixing 2,3-O-isopropylidene diethyl tartrate, a solvent and a reducer at 0-5 DEG C, preserving heat at 0-70 DEG C, performing reduction reaction for 16-36 hours, preserving heat, and adding a quenching agent for quenching reaction to obtain 2,3-O-isopropylidene threitol. The purification method comprises the steps of performing reduced pressure distillation on a crude product of 2,3-O-isopropylidene threitol, collecting fractions at 140-170 DEG C, uniformly dispersing the fractions with ethanol, adding dry ice, uniformly mixing, and separating out white solids, namely purified 2,3-O-isopropylidene threitol. The method is simple in process, low in production cost and high in product yield, and has an important application value.
Description
Technical field
The present invention relates to one and prepare and purifying 2, the method for 3-O-isopropylidene threitol.
Background technology
2,3-O-isopropylidene threitol is a kind of widely used medicine intermediate containing chirality, and its preparation is normally reacted and prepared 2 with 2,2-dimethoxypropane by dimethyl tartrate, 3-O-isopropylidene dimethyl tartrate, then prepare through the reduction such as lithium aluminium hydride or sodium borohydride.What bibliographical information selection was at present maximum is that the method advantage is that reduction reaction by product is few with lithium aluminium hydride or the reduction of red aurin tricarboxylic acid, and yield is higher, and shortcoming is that reductive agent is more expensive, and cost is higher.Separately there is bibliographical information, use sodium borohydride at methanol system, the reducible product that obtains higher yields.But such post-reaction treatment is more loaded down with trivial details, need to react with water decomposition cancellation, and the alkali generating and remaining sodium borohydride are used after acid neutralization, could reclaim solvent and the concentrated crude product that obtains product, and the nature of this compound: soluble in water, so be difficult to organic solvent, product be extracted in water.And because this compound stability is poor.So in acid, alkalescence, have water in the situation that, heating all can destroy its structure generation.
Having retrieved at present domestic and international report substantially can affirm and not yet have 2 of high-quality, the large suitability for industrialized production of 3-O-isopropylidene threitol, which kind of method reduction its Major Difficulties is no matter to use, its aftertreatment all needs to introduce a certain amount of water, just need to from water, product be extracted, need to use more organic solvent, therefore solvent consumption is large, yield is low, complex production process.In addition, bibliographical information most purified has all been selected column chromatography, and the efficiency of column chromatography and cost are very large in industrial limitation, is difficult for amplifying scale production.Only there is extremely else report use efficient vacuum pump distillation, to the 0.5mmHg that requires of vacuum tightness, will reach this requirement and have certain difficulty industrial.
Summary of the invention
The object of this invention is to provide one and prepare and purifying 2, the method for 3-O-isopropylidene threitol.
Preparation 2 provided by the invention, the method of 3-O-isopropoxy threitol, comprise the steps: 2,3-O-isopropylidene diethyl tartrate, solvent and reductive agent 0-5 ℃ mix after after 0-70 ℃ of insulation carried out reduction reaction 16-36 hour insulation add quencher to carry out cancellation reaction, obtain described 2,3-O-isopropoxy threitol.
In aforesaid method, described solvent is selected from least one in methyl alcohol, ethanol and Virahol; Or,
Described reductive agent is selected from least one in sodium borohydride, POTASSIUM BOROHYDRIDE, tetrahydrochysene lithium aluminium, red aluminium and palladium carbon; Or,
Described quencher is selected from least one in Glacial acetic acid, dilute hydrochloric acid, dilute sulphuric acid and aqueous ammonium chloride solution.The water that can make system produce that adds of quencher drops to minimum.
Described 2, the mass ratio of 3-O-isopropylidene diethyl tartrate, solvent, reductive agent and quencher is 65-80:180-220:19.4-23.7:33-40, preferably 70:200:21.5:36.
Described reductive agent adds in batches, and number of times is 3-7, and preferably 5, each add-on is 1/7th to 1/3rd of total add-on, and preferably 1/5th, be 3-8 minute each interval time, preferably 5 minutes.
In described reduction reaction step, temperature is specially 60 ℃; Time is specially 16,24,36,16-24 or 24-36 hour;
Described method also comprises the step of following recovery solvent: after described cancellation reaction, collect respectively solid and remaining liquid that reaction system is separated out, to adding in described remaining liquid, to carry out underpressure distillation to system temperature after ethanol be 100 ℃, completes the step of described recovery solvent.
The add-on of described ethanol is the 30-40% of described remaining liquid mass, is specially 35%.Adding can make to reclaim solvent time of ethanol can be produced azeotropic, and the water in system can just be use up by alcohol band at the distillation initial stage as early as possible, make product destroyed drop to minimum.
Purifying 2 provided by the invention, the method of 3-O-isopropoxy threitol, comprise the steps: that the solid that aforementioned approaches method is separated out in reaction system after described cancellation reaction carries out underpressure distillation, collect the cut of 140-170 ℃, described cut is uniformly dispersed with ethanol, then adds dry ice to mix, separate out solid, be 2 after purifying, 3-O-isopropoxy threitol.
In aforesaid method, the consumption of described ethanol is the 80-120% of the solid masses of separating out in described reaction system, preferably 100%;
The consumption of described dry ice is the 10-50% of ethanol quality used, preferably 30-33%;
In described underpressure distillation step, vacuum tightness is 10mmHg.
Preparation 2 provided by the invention, the method for 3-O-isopropylidene threitol, technique is simple, and production cost is low, and products collection efficiency is high; And the use of dry ice can make solution system turn cold rapidly in purification step, and the effect of having played crystal seed of short grained dry ice is conducive to the formation of crystallization, and dry ice is finally gasified totally and do not introduce other materials in solution, has important using value.
Embodiment
Below in conjunction with specific embodiment, the present invention is further elaborated, but the present invention is not limited to following examples.Described method is ordinary method if no special instructions.Described starting material all can obtain from open commercial sources if no special instructions.
In following embodiment, product 2, the measuring method of the purity of 3-O-isopropylidene threitol is GC method, and concrete testing conditions is as follows: chromatographic column: HP-530m × 0.32mm, δ=0.25um; Column temperature: 130 ℃, 2.5min; 10 ℃/min; 240 ℃, 10min; 240 ℃, 26min; Sample introduction temperature: 240 ℃; Detected temperatures: 260 ℃; Flow velocity (He): 1.0ml/min; Supplement gas (N
2): 30ml/min; H
2: 40ml/min; Air: 400ml/min; Splitting ratio: Y100.
Embodiment 1
To suction 70kg2 in 500L reactor, 3-O-isopropylidene diethyl tartrate, 200kg methyl alcohol, open and stir, be cooled to 0 ℃ with icy salt solution, add sodium borohydride 21.5Kg(to divide five times in batches, add 4Kg at every turn, every minor tick 5 minutes), control 0 ℃ of temperature, add 60 ℃ of insulations and carry out reduction reaction after 16 hours, 60 ℃ of temperature controls, drip 36kg Glacial acetic acid cancellation reaction, dripping off rear system has a large amount of white solids to separate out, centrifugal, collect respectively solid and remaining liquid that reaction system is separated out, remaining liquid suction 500L is reclaimed to still and add 100kg ethanol (be also remaining liquid mass 35%), water rushes pump decompression and solvent recovery to 100 ℃ of liquid temperatures, till going out cut hardly.Obtain 50Kg2,3-O-isopropoxy threitol crude product, sample presentation detects, and packs into and in plastic tank, treats underpressure distillation.
Underpressure distillation:
By gained 2,3-O-isopropoxy threitol crude product, mechanical pump underpressure distillation (vacuum tightness is 10mmHg), collects the cut of 140-170 ℃, obtains 45kg2,3-O-isopropoxy threitol, sample presentation detects GC, purity: >90%.
Recrystallization
By 2, after 3-O-isopropoxy threitol 45kg distillation, product adds 45kg ethanol, stirs molten clearly, controls stirring velocity 15-60 and turns, be sprinkled into dry ice 15kg, stir 20 minutes, a large amount of white solids are separated out, centrifugal fast, obtain 38kg product 2,3-O-isopropoxy threitol, sample presentation detects GC, purity: >=99%.
The structural confirmation data of this product are as follows:
1H?NMR(300MHz,D2O)δ3.69-3.51(m,6H).
13C?NMR(75MHz,D2O)
δ72.9,63.9.[α]
22=-7.5（c=0.5,MeOH）。
As from the foregoing, this product structure is correct, is 2,3-O-isopropoxy threitol.
Embodiment 2
To suction 70kg2 in 500L reactor, 3-O-isopropylidene diethyl tartrate, 200kg methyl alcohol, opens and stirs, and is cooled to 0 ℃ with icy salt solution, adds sodium borohydride 21.5Kg(to divide five times in batches, adds 4Kg, every minor tick 5 minutes at every turn), control 0 ℃ of temperature.Add 60 ℃ of insulations and carry out reduction reaction after 36 hours, 60 ℃ of temperature controls, drip 36kg Glacial acetic acid cancellation reaction, dripping off rear system has a large amount of white solids to separate out, centrifugal, collect respectively solid and remaining liquid that reaction system is separated out, remaining liquid suction 500L is reclaimed to still and add 100kg ethanol (be also remaining liquid mass 35%), water rushes pump decompression and solvent recovery to 100 ℃ of liquid temperatures, till going out cut hardly, obtain 55Kg2,3-O-isopropoxy threitol crude product, sample presentation detects, and packs into and in plastic tank, treats underpressure distillation.
Underpressure distillation:
By gained 2,3-O-isopropoxy threitol crude product, mechanical pump underpressure distillation (vacuum tightness is 10mmHg), collects the cut of 140-170 ℃, obtains 49kg2,3-O-isopropoxy threitol, sample presentation detects GC, purity: >90%.
Recrystallization
By 2, after 3-O-isopropoxy threitol 49kg distillation, product adds 49kg ethanol, stirs molten clearly, controls stirring velocity 15-60 and turns, be sprinkled into dry ice 15kg, stir 20 minutes, a large amount of white solids are separated out, centrifugal fast, obtain 42kg product 2,3-O-isopropoxy threitol, sample presentation detects GC, purity: >=99%.
The structural confirmation data of this product are as follows:
1H?NMR(300MHz,D2O)δ3.69-3.51(m,6H).
13C?NMR(75MHz,D2O)
δ72.9,63.9.[α]
22=-7.5（c=0.5,MeOH）。
As from the foregoing, this product structure is correct, is 2,3-O-isopropoxy threitol.
Embodiment 3
To suction 70kg2 in 500L reactor, 3-O-isopropylidene diethyl tartrate, 200kg methyl alcohol, opens and stirs, and is cooled to 0 ℃ with icy salt solution, adds sodium borohydride 21.5Kg(to divide five times in batches, adds 4Kg, every minor tick 5 minutes at every turn), control 0 ℃ of temperature.Add 60 ℃ of insulations and carry out reduction reaction after 24 hours, 60 ℃ of temperature controls, drip 36kg Glacial acetic acid cancellation reaction, dripping off rear system has a large amount of white solids to separate out, centrifugal, collect respectively solid and remaining liquid that reaction system is separated out, remaining liquid suction 500L is reclaimed to still and add 100kg ethanol (be also remaining liquid mass 35%), water rushes pump decompression and solvent recovery to 100 ℃ of liquid temperatures, till going out cut hardly.Obtain 52Kg2,3-O-isopropoxy threitol crude product, sample presentation detects, and packs into and in plastic tank, treats underpressure distillation.
Underpressure distillation:
By gained 2,3-O-isopropoxy threitol crude product, mechanical pump underpressure distillation (vacuum tightness is 10mmHg), collects the cut of 140-170 ℃, obtains 47kg2,3-O-isopropoxy threitol, sample presentation detects GC, purity: >90%.
Recrystallization
By 2, after 3-O-isopropoxy threitol 47kg distillation, product adds 47kg ethanol, stirs molten clearly, controls stirring velocity 15-60 and turns, be sprinkled into dry ice 15kg, stir 20 minutes, a large amount of white solids are separated out, centrifugal fast, obtain 40kg product 2,3-O-isopropoxy threitol, sample presentation detects GC, purity: >=99%.
The structural confirmation data of this product are as follows:
1H?NMR(300MHz,D2O)δ3.69-3.51(m,6H).
13C?NMR(75MHz,D2O)
δ72.9,63.9.[α]
22=-7.5（c=0.5,MeOH）。
As from the foregoing, this product structure is correct, is 2,3-O-isopropoxy threitol.
Claims (8)
1. prepare 2 for one kind, the method of 3-O-isopropoxy threitol, comprise the steps: 2,3-O-isopropylidene diethyl tartrate, solvent and reductive agent 0-5 ℃ mix after after 0-70 ℃ of insulation carried out reduction reaction 16-36 hour insulation add quencher to carry out cancellation reaction, obtain described 2,3-O-isopropoxy threitol.
2. method according to claim 1, is characterized in that: described solvent is selected from least one in methyl alcohol, ethanol and Virahol; Or,
Described reductive agent is selected from least one in sodium borohydride, POTASSIUM BOROHYDRIDE, tetrahydrochysene lithium aluminium, red aluminium and palladium carbon; Or,
Described quencher is selected from least one in Glacial acetic acid, dilute hydrochloric acid, dilute sulphuric acid and aqueous ammonium chloride solution.
3. method according to claim 1 and 2, it is characterized in that: described 2, the mass ratio of 3-O-isopropylidene diethyl tartrate, solvent, reductive agent and quencher is 65-80:180-220:19.4-23.7:33-40, is specially 70:200:21.5:36.
4. according to the arbitrary described method of claim 1-3, it is characterized in that: described reductive agent adds in batches, number of times is 3-7, be specially 5, each add-on is 1/7th to 1/3rd of total add-on, be specially 1/5th, be 3-8 minute each interval time, is specially 5 minutes;
In described reduction reaction step, temperature is 60 ℃; Time is 16,24,36,16-24 or 24-36 hour.
5. according to the arbitrary described method of claim 1-4, it is characterized in that: described method also comprises the step of following recovery solvent: after described cancellation reaction, collect respectively solid and remaining liquid that reaction system is separated out, to adding in described remaining liquid, to carry out underpressure distillation to system temperature after ethanol be 100 ℃, completes the step of described recovery solvent.
6. method according to claim 5, is characterized in that: the 30-40% that the add-on of described ethanol is described remaining liquid mass, is specially 35%.
7. a purifying 2, the method of 3-O-isopropoxy threitol, comprise the steps: that the solid to separating out in reaction system in the arbitrary described method of claim 1-6 carries out underpressure distillation after described cancellation reaction, collect the cut of 140-170 ℃, described cut is uniformly dispersed with ethanol, then adds dry ice to mix, separate out solid, be 2 after purifying, 3-O-isopropoxy threitol.
8. method according to claim 7, is characterized in that: the consumption of described ethanol is the 80-120% of the solid masses of separating out in described reaction system, is specially 100%;
The consumption of described dry ice is the 10-50% of ethanol quality used, is specially 30-33%;
In described underpressure distillation step, vacuum tightness is 10mmHg.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310705598.XA CN103896903A (en) | 2012-12-26 | 2013-12-19 | Method for preparing and purifying 2,3-O-isopropylidene threitol |
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| CN201210575354 | 2012-12-26 | ||
| CN201210575354.X | 2012-12-26 | ||
| CN201310705598.XA CN103896903A (en) | 2012-12-26 | 2013-12-19 | Method for preparing and purifying 2,3-O-isopropylidene threitol |
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| CN103896903A true CN103896903A (en) | 2014-07-02 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113620922A (en) * | 2021-08-12 | 2021-11-09 | 郑州轻工业大学 | Synthetic method of threitol-based polyurethane |
| CN115650823A (en) * | 2022-09-07 | 2023-01-31 | 太原理工大学 | Method for purifying ethylene glycol |
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| US3246012A (en) * | 1961-09-15 | 1966-04-12 | Lphivens Kemiske Fabrik Ved A | L-threo-1, 3-dioxolane |
| CN103073462A (en) * | 2013-01-12 | 2013-05-01 | 江西师范大学 | Preparation method of dithiothreitol |
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2013
- 2013-12-19 CN CN201310705598.XA patent/CN103896903A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3246012A (en) * | 1961-09-15 | 1966-04-12 | Lphivens Kemiske Fabrik Ved A | L-threo-1, 3-dioxolane |
| CN103073462A (en) * | 2013-01-12 | 2013-05-01 | 江西师范大学 | Preparation method of dithiothreitol |
Non-Patent Citations (2)
| Title |
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| 徐国春等: "手性双膦配体（4S，5S）-（－）-DIOP的合成", 《高等学校化学学报》 * |
| 杨行忠等: "均相催化氢化的研究I.不对称催化剂（4R，5R）（＋）及（4S，5S）（－）DIOP-铑的合成", 《化学试剂》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113620922A (en) * | 2021-08-12 | 2021-11-09 | 郑州轻工业大学 | Synthetic method of threitol-based polyurethane |
| CN115650823A (en) * | 2022-09-07 | 2023-01-31 | 太原理工大学 | Method for purifying ethylene glycol |
| CN115650823B (en) * | 2022-09-07 | 2024-01-23 | 太原理工大学 | Method for purifying ethylene glycol |
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Application publication date: 20140702 |