CN102229584A - Method for preparing D-(-)- or L-(+)-pantoic acid lactone by splitting pantoic acid lactone - Google Patents
Method for preparing D-(-)- or L-(+)-pantoic acid lactone by splitting pantoic acid lactone Download PDFInfo
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- CN102229584A CN102229584A CN2011100979507A CN201110097950A CN102229584A CN 102229584 A CN102229584 A CN 102229584A CN 2011100979507 A CN2011100979507 A CN 2011100979507A CN 201110097950 A CN201110097950 A CN 201110097950A CN 102229584 A CN102229584 A CN 102229584A
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Abstract
The invention discloses a method for preparing D-(-)- or L-(+)-pantoic acid lactone by splitting pantoic acid lactone. The method comprises the following steps of: preparing the pantoic acid lactone into solution by using water and/or methylbenzene as a solvent; under the conditions of stirring and proper temperature, adding a D-(-)-pantoic acid lactone crystal or an L-(+)-pantoic acid lactone crystal serving as a seed crystal to induce with stirring; in the stirring process, sampling a system and performing suction-filtration on the system to monitor optical rotation of the filtrate; cooling and stirring when the optical rotation does not exceed the specified value; monitoring when the optical rotation does not exceed the specified value; performing suction-filtration to obtain a crystal; and recrystallizing the crystal until the specific optical rotation accords with the requirement so as to obtain the targeted product. By the method, the defect that a splitting reagent is difficult to recover by the traditional industrial method is overcome; the production process is relatively simple; the splitting efficiency is high; and mother liquid can be recycled, so production cost is greatly reduced.
Description
Technical field
The present invention relates to a kind of method that splits pantoyl lactone, be specifically related to a kind ofly split pantoyl lactone and prepare D-(-)-or the method for L-(+)-pantoyl lactone by inducing.
Summary of the invention
The chemical name of D-pantoyl lactone is Alpha-hydroxy-β, and beta-dimethyl-gamma-butyrolactone alpha-hydroxy-beta as a kind of important medicine intermediate, is mainly used in synthesise vitamins class medicine D-panthenol and neurotrophy medicine D-calcium pantothenate.The D-calcium pantothenate is a vitamin B5, as important nutritive ingredient, is widely used in fodder additives, foodstuff additive, medicine and other fields; D-panthenol is pro-vitamin B5, is widely used in hair care articles and the makeup.
The traditional industry method of preparation D-pantoyl lactone is chemical resolution method and biological Split Method, these two kinds of method production process complexity, and the resolution reagent preparation is reclaimed loaded down with trivial details, the production cost height.Along with the continuous expansion in D-panthenol, D-calcium pantothenate market, the demand of D-pantoyl lactone increases day by day.Seek its new method for splitting, improve production technique, improve the quality of products, become the purpose that the investigator and the producer pursue always.
Summary of the invention
The objective of the invention is to remedy the deficiency of prior art, provide a kind of fractionation pantoyl lactone to prepare D-(-)-or the method for L-(+)-pantoyl lactone, this method is by inducing the mode of fractionation, operation is simple relatively, avoided the traditional method resolution reagent to reclaim the shortcoming of difficulty, and can circulation-induced go down, production cost is low.
Realize that the technical scheme that above-mentioned purpose of the present invention adopted is: a kind of fractionation pantoyl lactone prepares D-(-)-or the method for L-(+)-pantoyl lactone, may further comprise the steps:
(1) obtain solution: with water and/or toluene as solvent, it is that the mass percent concentration of G1 is 76～88% pantoyl lactone solution that pantoyl lactone is made into weight, when making solvent with water and toluene, the mass percent of water in pantoyl lactone solution is 0.85～2.05%; Described pantoyl lactone is the DL-pantoyl lactone or is the opticity pantoyl lactone, and when being the opticity pantoyl lactone, with water and/or toluene as solvent, it is made into after mass percent concentration is 76～88% pantoyl lactone solution, solution sampling suction filtration is charged into filtrate in the 10cm polarization tube, with the sodium light is light source, and under 25 ℃ of conditions, dextral specific rotation is no more than+and 5.5 ° or left-handed specific rotation be no more than-5.5 °;
(2) add crystal seed, induce:
A. select crystal seed: when pantoyl lactone is the DL-pantoyl lactone, with D-(-)-pantoyl lactone crystal or L-(+)-pantoyl lactone crystal as crystal seed, when pantoyl lactone solution when being left-handed, with D-(-)-pantoyl lactone crystal as crystal seed, when pantoyl lactone solution is dextrorotation, with L-(+)-pantoyl lactone crystal as crystal seed;
B. add crystal seed: under agitation condition, adding 50～100 purpose weight in 13～15 ℃ in pantoyl lactone solution is the crystal seed of G2, and the consumption of crystal seed is 0.7～1.9% of pantoyl lactone solution weight G1;
C. induce: keep 10～15 ℃ of continuation to stir and induce, when the crystal seed that adds as step b is D-(-)-pantoyl lactone crystal, sampling suction filtration and filtrate charged in the 10cm polarization tube in the whipping process, with the sodium light is light source, 25 ℃ of specific rotatioies that detect filtrates are no more than+and 2 °, the icy salt solution of using-2 ℃～2 ℃ then is that the cooling medium continues the cooling stirring, the suction filtration of taking a sample in the whipping process, employing with the specific rotation that quadrat method detects filtrate be no more than+5.5 °, when perhaps the crystal seed that adds as step b is L-(+)-pantoyl lactone crystal, sampling suction filtration and filtrate charged in the 10cm polarization tube in the whipping process, with the sodium light is light source, 25 ℃ of specific rotatioies that detect filtrate are no more than-2 °, the icy salt solution of using-2 ℃～2 ℃ then is that the cooling medium continues the cooling stirring, the suction filtration of taking a sample in the whipping process, employing is no more than-5.5 ° with the specific rotation that quadrat method detects filtrate, at last the system suction filtration is obtained the xln that weight is G3, gained weight is that the filtrate of G4 is as mother liquor;
(3) recrystallization, detection specific rotatory power:
D. recrystallization: with suction filtration gained xln with after toluene or o-Xylol mix, intensification makes the xln dissolving, under agitation condition, in 9～10 ℃ of coolings, time is no less than 45 minutes, in-2～2 ℃ of coolings, the time is no less than 45 minutes again, treats that then system temperature is no more than suction filtration under 5 ℃ the condition;
E. detect the specific rotatory power of products therefrom behind the recrystallization: when the crystal seed that adds among the step b is D-(-)-pantoyl lactone crystal, if the specific rotatory power of product
D recrystallization once more set by step then, so repeatedly for several times, until the specific rotatory power of product
Obtain D-(-)-pantoyl lactone, perhaps when the crystal seed that adds among the step b is L-(+)-pantoyl lactone crystal, if the specific rotatory power of product
D recrystallization once more set by step then, so repeatedly for several times, until the specific rotatory power of product
Obtain L-(+)-pantoyl lactone.
When the crystal seed that adds among the step b is D-(-)-pantoyl lactone crystal, in mother liquor, replenish weight and be G3 pantoyl lactone and with equiponderant water of system loss amount G and/or toluene, be warming up to 30～70 ℃ of dissolvings, then under agitation condition, add 50～100 purpose L-(+)-pantoyl lactone crystal in 13～15 ℃, c induces set by step, and (3) recrystallization, detection specific rotatory power obtain L-(+)-pantoyl lactone more set by step; Described system loss amount is gross weight poor of the gross weight of pantoyl lactone solution and step crystal seed that b adds in the step (1) and step c gained xln and mother liquor, i.e. G=G1+G2-G3-G4.
When the crystal seed that adds among the step b is L-(+)-pantoyl lactone crystal, in mother liquor, replenish weight and be G3 pantoyl lactone and with equiponderant water of system loss amount G and/or toluene, be warming up to 30～70 ℃ of dissolvings, then under agitation condition, add 50～100 purpose D-(-)-pantoyl lactone crystal in 13～15 ℃, c induces set by step, and (3) recrystallization, detection specific rotatory power obtain D-(-)-pantoyl lactone more set by step; Described system loss amount is gross weight poor of the gross weight of pantoyl lactone solution and step crystal seed that b adds in the step (1) and step c gained xln and mother liquor, i.e. G=G1+G2-G3-G4.
The purity of described DL-pantoyl lactone or D-(-)-pantoyl lactone or L-(+)-pantoyl lactone is not less than 96.5%.
Described opticity pantoyl lactone is D-(-)-pantoyl lactone and L-(+)-pantoyl lactone inequality blended mixture, perhaps is D-(-)-pantoyl lactone of DL-pantoyl lactone and inequality and L-(+)-pantoyl lactone three's mixture.
In the step (1) be with water and/or toluene as solvent, the mass percent concentration that pantoyl lactone is made into weight under 30～70 ℃ of conditions and is G1 is 76～88% pantoyl lactone solution.
In the steps d with suction filtration gained xln with after toluene or o-Xylol mix, be warming up to 30～70 ℃ and make the xln dissolving.
The speed of described stirring is 20～150 rev/mins.
With specific rotatory power
For+20 °～+ 30 ° or
Be-30 °～-20 ° xln set by step during the d recrystallization, the mass ratio of xln and toluene or o-Xylol is 4: 1.During recrystallization, the consumption capacity of toluene or o-Xylol gets final product, but adopts this kind consumption proportion most economical.
With specific rotatory power
Greater than+30 ° or
Set by step during the d recrystallization, the mass ratio of xln and toluene or o-Xylol is 2: 1 less than-30.0 ° xln.During recrystallization, the consumption capacity of toluene or o-Xylol gets final product, but adopts this kind consumption proportion most economical.
The inventive method is that (pantoyl lactone among the present invention is the DL-pantoyl lactone or is the opticity pantoyl lactone with pantoyl lactone earlier, and when being the opticity pantoyl lactone, with water and/or toluene as solvent, it is made into after mass percent concentration is 76～88% pantoyl lactone solution, solution sampling suction filtration is charged into filtrate in the 10cm polarization tube, with the sodium light is light source, and under 25 ℃ of conditions, dextral specific rotation is no more than+and 5.5 ° or left-handed specific rotation be no more than-5.5 °.The opticity pantoyl lactone is D-(-)-pantoyl lactone and L-(+)-pantoyl lactone inequality blended mixture, perhaps is D-(-)-pantoyl lactone of DL-pantoyl lactone and inequality and L-(+)-pantoyl lactone three's mixture.) be made into certain density pantoyl lactone solution; When pantoyl lactone is the DL-pantoyl lactone, with D-(-)-pantoyl lactone crystal or L-(+)-pantoyl lactone crystal as crystal seed, when pantoyl lactone solution when being left-handed, with D-(-)-pantoyl lactone crystal as crystal seed, when pantoyl lactone solution is dextrorotation, with L-(+)-pantoyl lactone crystal as crystal seed, in the pantoyl lactone solution for preparing, add crystal seed, pantoyl lactone is induced, obtain xln behind the suction filtration, with xln recrystallization several times, reach requirement until its specific rotatory power, obtain corresponding D-(-)-pantoyl lactone or L-(+)-pantoyl lactone.Each use with again the filtrate of system suction filtration gained being can be used as Recycling Mother Solution again after-2 ℃～2 ℃ the icy salt solution cooling, when the crystal seed of for the first time inducing adding is D-(-)-pantoyl lactone crystal, in mother liquor, replenish with induce the suction filtration equiponderant pantoyl lactone of final gained xln and with the equiponderant solvent of system loss amount (the system loss amount refers to the pantoyl lactone solution that begins to prepare and institute and adds the gross weight of crystal seed and induce and detect gross weight poor that specific rotation reaches suction filtration gained xln and mother liquor after the requirement), adding L-(+)-pantoyl lactone again induces, suction filtration, recrystallization, reach requirement until specific rotatory power, obtain L-(+)-pantoyl lactone; The crystal seed that adds when inducing for the first time is L-(+)-pantoyl lactone crystal, then in mother liquor, replenish with induce for the first time the equiponderant pantoyl lactone of the final gained xln of suction filtration and with the equiponderant solvent of system loss amount, add again that D-(-)-pantoyl lactone is induced, suction filtration, recrystallization, reach requirement until specific rotatory power, obtain D-(-)-pantoyl lactone.Mother liquor can be used for carrying out next round again induces, and the circulation-induced crystallization is gone down like this, repeatedly splits efficient constantly near theoretical value (50%) after the circulation.
Therefore, compared with prior art, the present invention has the following advantages:
1. the inventive method is only used cheap a small amount of solvent and is realized fractionation, circulation time splits efficient with respect to the substrate single can reach 42.81～56.92%, and mother liquor can recycle, gained L-(+)-pantoyl lactone crystal can become the DL-pantoyl lactone by racemization, by vacuum distilling purification back cyclically utilizing, reduced production cost significantly.
2. the inventive method is not used resolution reagent, has avoided existing commercial run that resolution reagent is reclaimed difficult defective, and production technique is simple relatively.
Embodiment
The present invention is further illustrated below by specific embodiment, but protection content of the present invention is not limited to following examples.
In following examples if no special instructions, used percentage concentration is mass percent concentration, the purity (referring to chemical purity) of DL-pantoyl lactone or D-(-)-pantoyl lactone or L-(+)-pantoyl lactone all is not less than 96.5%, and stirring velocity is 20～150 rev/mins.
Embodiment 1
DL-pantoyl lactone 720g, toluene 180ml and water 11ml are mixed, and the mass percent concentration that obtains water content 1.24% is 81.2% pantoyl lactone solution, and it is warming up to 60 ℃ of dissolvings.Under agitation condition, in the time of 15 ℃, in above-mentioned solution, add 12g 50～100 purpose D-(-)-pantoyl lactone crystal as crystal seed, holding temperature stirs down for 10～15 ℃, monitor specific rotation in the whipping process, concrete grammar is: the sampling suction filtration charges into filtrate in the 10cm polarization tube, with the sodium light is light source, detects specific rotation under 25 ℃ of conditions.Stir after 4 hours, detecting the filtrate specific rotation is+1.62 °, uses 0 ℃ ± 2 ℃ icy salt solution cooling to stir then, adopts in the whipping process and above-mentioned same method monitoring specific rotation, stirs after 4.5 hours, and the specific rotation that sampling detects filtrate is+5.45 °.In order to reduce the system loss amount as far as possible, can be after each sampling suction filtration has detected specific rotation gained filter cake and filtrate be refunded again and induce in the system.To induce the system suction filtration at last, get xln 142g, survey its specific rotatory power
Suction filtration gained filtrate obtains mother liquor 736g as mother liquor.Get suction filtration gained xln 100g, 25g mixes with toluene, is warming up to 60 ℃ of dissolvings, under agitation condition, after 45 minutes, use 0 ℃ ± 2 ℃ icy salt solution to lower the temperature again 45 minutes in 9～10 ℃ of coolings, suction filtration when treating that system temperature is 5 ℃, crystal 6 6.5g, survey this crystalline specific rotatory power
With specific rotatory power
Crystal 6 6.5g mix with toluene 33g, be warming up to 65 ℃ of dissolvings, under agitation condition, in 9～10 ℃ of coolings after 45 minutes, use 0 ℃ ± 2 ℃ icy salt solution cooling 45 minutes again, suction filtration and air-dry when treating that system temperature is 5 ℃, get crystal 4 9.2g, record this crystalline specific rotatory power
Contrast (the specific rotatory power of standard substance with D-(-)-pantoyl lactone standard substance
), confirm that the final products obtained therefrom of present embodiment is D-(-)-pantoyl lactone.The initial fractionation efficient that circulates is (49.2 * 142 ÷ 100-12) ÷ 720 * 100%=8.03%.
Embodiment 2
In embodiment 1 is mother liquid obtained, add DL-pantoyl lactone 142g, toluene 22ml and water 2ml, be made into water content 1.35% concentration and be 81.4% pantoyl lactone solution, be warming up to 50 ℃ of dissolvings.Under agitation condition, in the time of 15 ℃, in above-mentioned solution, add 14g 50～100 purpose L-(+)-pantoyl lactone crystal as crystal seed, holding temperature stirs down for 10～15 ℃, adopt the method identical to monitor specific rotation with embodiment 1, stirring the detection filtrate specific rotation of taking a sample after 4 hours is-1.8 °, use 0 ℃ ± 2 ℃ icy salt solution cooling to stir again, adopt in the whipping process with quadrat method monitoring specific rotation, stirring the detection filtrate specific rotation of taking a sample after 2.5 hours is-3.95 °, to induce the system suction filtration at last, get xln 202g, survey its specific rotatory power
Suction filtration gained filtrate 669g is as mother liquor.Get specific rotatory power
Xln 100g mix with toluene 25g, be warming up to 65 ℃ of dissolvings, under agitation condition, in 9～10 ℃ of coolings after 45 minutes, use 0 ℃ ± 2 ℃ icy salt solution cooling 60 minutes again, suction filtration when treating that system temperature is 4 ℃, get crystal 6 6.25g, record this crystalline specific rotatory power
With specific rotatory power
Crystal 6 6.25g mix with toluene 33g, be warming up to 65 ℃ of dissolvings, under agitation condition, in 9～10 ℃ of coolings after 45 minutes, use 0 ℃ ± 2 ℃ icy salt solution cooling 50 minutes again, suction filtration and air-dry when treating that system temperature is 4 ℃, get crystal 4 6.94g, record this crystalline specific rotatory power
Contrast (the specific rotatory power of standard substance with L-(+)-pantoyl lactone standard substance
), confirm that the present embodiment products obtained therefrom is L-(+)-pantoyl lactone.It is (46.94 * 202 ÷ 100-14) ÷ 142 * 100%=56.92% that circulation splits efficient.
Embodiment 3
Add DL-pantoyl lactone 202g and toluene 48ml in embodiment 2 is mother liquid obtained, being made into water content is that 1.28% concentration is 81.7% solution, is warming up to 48 ℃ of dissolvings.Under agitation condition, in the time of 13 ℃, in above-mentioned solution, add 16g 50～100 purpose D-(-)-pantoyl lactone crystal as crystal seed, under 10～15 ℃ of the holding temperatures, adopt the method identical to monitor specific rotation with embodiment 1, stirring the detection filtrate specific rotation of taking a sample after 4 hours is+2.0 °, use 0 ℃ ± 2 ℃ icy salt solution cooling to stir again, adopt in the whipping process with quadrat method monitoring specific rotation, stirring the detection filtrate specific rotation of taking a sample after 4 hours is+4.95 °, suction filtration, get xln 210g, survey its specific rotatory power
Suction filtration gained filtrate 665g is as mother liquor.Get suction filtration gained specific rotatory power
Xln 100g, 25g mixes with toluene, is warming up to 55 ℃ of dissolvings, under agitation condition, after 45 minutes, use 0 ℃ ± 2 ℃ icy salt solution to lower the temperature again 45 minutes in 9～10 ℃ of coolings, suction filtration when treating that system temperature is 5 ℃, crystal 6 6.1g, record this crystalline specific rotatory power
With specific rotatory power
Crystal 6 6.1g mix with toluene 33g, be warming up to 55 ℃ of dissolvings, under agitation condition, in 9～10 ℃ of coolings after 45 minutes, use 0 ℃ ± 2 ℃ icy salt solution cooling 45 minutes again, suction filtration and air-dry when treating that system temperature is 3 ℃, get crystal 4 8.8g, record this crystalline specific rotatory power
Contrast (the specific rotatory power of standard substance with D-(-)-pantoyl lactone standard substance
), confirm that the gained crystal is D-(-)-pantoyl lactone.It is (48.8 * 210 ÷ 100-16) ÷ 202 * 100%=42.81% that circulation splits efficient.
Embodiment 4
With toluene be the solvent pantoyl lactone 665g that will have opticity (this pantoyl lactone be DL pantoyl lactone 600g,
D-(-)-pantoyl lactone 19g,
L-(+)-pantoyl lactone 46g three's mixture), be warming up to 60 ℃ of dissolvings, be made into concentration and be 86.27% solution, its sampling suction filtration is charged into filtrate in the 10cm polarization tube, with the sodium light is light source, and under 25 ℃ of conditions, the specific rotation that records filtrate is+3.0 °.Get above-mentioned concentration and be 86.27% solution 770g, under agitation condition, in the time of 14 ℃, in above-mentioned solution, add 62g 50～100 purpose L-(+)-pantoyl lactone crystal as crystal seed, under 10～15 ℃ of the holding temperatures, adopt the method identical to monitor specific rotation with embodiment 1, stirring the detection filtrate specific rotation of taking a sample after 1.5 hours is-1.61 °, use 0 ℃ ± 2 ℃ icy salt solution cooling to stir again, adopt in the whipping process with quadrat method monitoring specific rotation, stirring the detection filtrate specific rotation of taking a sample after 4.5 hours is-4.86 °, suction filtration obtains xln 147g, surveys its specific rotatory power
Suction filtration gained filtrate 619g is as mother liquor.Get suction filtration gained specific rotatory power
Xln 100g mix with toluene 25g, be warming up to 65 ℃ of dissolvings, under agitation condition, in 9～10 ℃ of coolings after 45 minutes, use 0 ℃ ± 2 ℃ icy salt solution cooling 45 minutes again, suction filtration when treating that system temperature is 5 ℃, get crystal 6 5.8g, record this crystalline specific rotatory power
With specific rotatory power
Crystal 6 5.8g mix with toluene 33g, be warming up to 55 ℃ of dissolvings, under agitation condition, in 9～10 ℃ of coolings after 45 minutes, use 0 ℃ ± 2 ℃ icy salt solution cooling 63 minutes again, suction filtration and air-dry when treating that system temperature is 5 ℃, get crystal 4 6.8g, record this crystalline specific rotatory power
Contrast (the specific rotatory power of standard substance with L-(+)-pantoyl lactone standard substance
), confirm that the gained crystal is L-(+)-pantoyl lactone.The initial fractionation efficient that circulates is (46.8 * 147 ÷ 100-6.2) ÷ (770 * 0.8627) * 100%=9.42%.
Embodiment 5
(this pantoyl lactone is to add pantoyl lactone 147g in the mother liquor of embodiment 4
D-(-)-pantoyl lactone 71g and
L-(+)-both mixtures of pantoyl lactone 76g) and toluene 11.8ml, be warming up to 56 ℃ of dissolvings, be made into concentration and be 86.39% solution, its sampling suction filtration is charged into filtrate in the 10cm polarization tube, with the sodium light is light source, and under 25 ℃ of conditions, the specific rotation that records filtrate is-4.5 °.Get concentration and be 86.39% solution 770g, under agitation condition, in the time of 13 ℃, in above-mentioned solution, add 6.3g50～100 purpose D-(-)-pantoyl lactone crystal as crystal seed, under 10～15 ℃ of the holding temperatures, adopt the method identical to monitor specific rotation with embodiment 1, stirring the detection filtrate specific rotation of taking a sample after 3 hours is+1.86 °, use 0 ℃ ± 2 ℃ icy salt solution cooling to stir again, adopt in the whipping process with quadrat method monitoring specific rotation, stirring the detection filtrate specific rotation of taking a sample after 6 hours is+4.56 °, suction filtration gets xln 156g, surveys its specific rotatory power
Suction filtration gained filtrate 608g can be used for inducing as mother liquor next time.Get suction filtration gained xln 100g, 25g mixes with toluene, is warming up to 63 ℃ of dissolvings, under agitation condition, after 45 minutes, use 0 ℃ ± 2 ℃ icy salt solution to lower the temperature again 45 minutes in 9～10 ℃ of coolings, suction filtration when treating that system temperature is 5 ℃, crystal 6 6g, record this crystalline specific rotatory power
With specific rotatory power
Crystal 6 6g mix with toluene 33g, be warming up to 56 ℃ of dissolvings, under agitation condition, in 9～10 ℃ of coolings after 52 minutes, use 0 ℃ ± 2 ℃ icy salt solution cooling 68 minutes again, suction filtration and air-dry when treating that system temperature is 5 ℃, get crystal 4 9g, record this crystalline specific rotatory power
Contrast (the specific rotatory power of standard substance with D-(-)-pantoyl lactone standard substance
), confirm that the gained crystal is D-(-)-pantoyl lactone.It is (49 * 156 ÷ 100-6.3) ÷ 147 * 100%=47.71% that circulation splits efficient.
Embodiment 6
DL-pantoyl lactone 1125g and water 355g are mixed, be warming up to 58 ℃ of dissolvings.Under agitation condition, in the time of 15 ℃, in above-mentioned solution, add 19g 50～100 purpose D-(-)-pantoyl lactone crystal as crystal seed, holding temperature stirs down for 10～15 ℃, adopt the method identical to monitor specific rotation in the whipping process with embodiment 1, stirring the detection filtrate specific rotation of taking a sample after 2 hours is+1.06 °, use 0 ℃ ± 2 ℃ icy salt solution cooling to stir again, adopt the method identical to monitor specific rotation in the whipping process with embodiment 1, stirring the detection filtrate specific rotation of taking a sample after 6 hours is+3.16 °, to induce the system suction filtration at last, get xln 100g, survey the specific rotatory power of this xln
Suction filtration gained filtrate is as mother liquor.Get suction filtration gained specific rotatory power
Xln 100g, 50g mixes with toluene, is warming up to 60 ℃ of dissolvings, under agitation condition, after 60 minutes, use 0 ℃ ± 2 ℃ icy salt solution to lower the temperature again 80 minutes in 9～10 ℃ of coolings, suction filtration and air-dry when treating that system temperature is 5 ℃, crystal 72g, record this crystalline specific rotatory power
Contrast (the specific rotatory power of standard substance with D-(-)-pantoyl lactone standard substance
Confirm that the gained crystal is D-(-)-pantoyl lactone.The initial fractionation efficient that circulates is (72-19) ÷ 1125 * 100%=4.71%.
In the embodiment of the invention during recrystallization used solvent be toluene, can also adopt o-Xylol.
Claims (10)
1. one kind splits pantoyl lactone and prepares D-(-)-or the method for L-(+)-pantoyl lactone, it is characterized in that this method specifically may further comprise the steps:
(1) join solution: with water and/or toluene as solvent, it is that the mass percent concentration of G1 is 76～88% pantoyl lactone solution that pantoyl lactone is made into weight, when making solvent with water and toluene, the mass percent of water in pantoyl lactone solution is 0.85～2.05%; Described pantoyl lactone is the DL-pantoyl lactone or is the opticity pantoyl lactone, and when being the opticity pantoyl lactone, with water and/or toluene as solvent, it is made into after mass percent concentration is 76～88% pantoyl lactone solution, solution sampling suction filtration is charged into filtrate in the 10cm polarization tube, with the sodium light is light source, and under 25 ℃ of conditions, dextral specific rotation is no more than+and 5.5 ° or left-handed specific rotation be no more than-5.5 °;
(2) add crystal seed, induce:
A. select crystal seed: when pantoyl lactone is the DL-pantoyl lactone, with D-(-)-pantoyl lactone crystal or L-(+)-pantoyl lactone crystal as crystal seed, when pantoyl lactone solution when being left-handed, with D-(-)-pantoyl lactone crystal as crystal seed, when pantoyl lactone solution is dextrorotation, with L-(+)-pantoyl lactone crystal as crystal seed;
B. add crystal seed: under agitation condition, adding 50～100 purpose weight in 13～15 ℃ in pantoyl lactone solution is the crystal seed of G2, and the consumption of crystal seed is 0.7～1.9% of pantoyl lactone solution weight G1;
C. induce: keep 10～15 ℃ of continuation to stir and induce, when the crystal seed that adds as step b is D-(-)-pantoyl lactone crystal, sampling suction filtration and filtrate charged in the 10cm polarization tube in the whipping process, with the sodium light is light source, 25 ℃ of specific rotatioies that detect filtrates are no more than+and 2 °, the icy salt solution of using-2 ℃～2 ℃ then is that the cooling medium continues the cooling stirring, the suction filtration of taking a sample in the whipping process, employing with the specific rotation that quadrat method detects filtrate be no more than+5.5 °, when perhaps the crystal seed that adds as step b is L-(+)-pantoyl lactone crystal, sampling suction filtration and filtrate charged in the 10cm polarization tube in the whipping process, with the sodium light is light source, 25 ℃ of specific rotatioies that detect filtrate are no more than-2 °, the icy salt solution of using-2 ℃～2 ℃ then is that the cooling medium continues the cooling stirring, the suction filtration of taking a sample in the whipping process, employing is no more than-5.5 ° with the specific rotation that quadrat method detects filtrate, last suction filtration obtains the xln that weight is G3, and gained weight is that the filtrate of G4 is as mother liquor;
(3) recrystallization, detection specific rotatory power:
D. recrystallization: with suction filtration gained xln with after toluene or o-Xylol mix, intensification makes the xln dissolving, under agitation condition, in 9～10 ℃ of coolings, time is no less than 45 minutes, in-2～2 ℃ of coolings, the time is no less than 45 minutes again, treats that then system temperature is no more than suction filtration under 5 ℃ the condition;
E. detect the specific rotatory power of products therefrom behind the recrystallization: when the crystal seed that adds among the step b is D-(-)-pantoyl lactone crystal, if the specific rotatory power of product
D recrystallization once more set by step then, so repeatedly for several times, until the specific rotatory power of product
Obtain D-(-)-pantoyl lactone, perhaps when the crystal seed that adds among the step b is L-(+)-pantoyl lactone crystal, if the specific rotatory power of product
D recrystallization once more set by step then, so repeatedly for several times, until the specific rotatory power of product
Obtain L-(+)-pantoyl lactone.
2. fractionation pantoyl lactone according to claim 1 prepares D-(-)-or the method for L-(+)-pantoyl lactone, it is characterized in that: when the crystal seed that adds among the step b is D-(-)-pantoyl lactone crystal, in mother liquor, replenish weight and be G3 pantoyl lactone and with equiponderant water of system loss amount G and/or toluene, be warming up to 30～70 ℃ of dissolvings, then under agitation condition, add 50～100 purpose L-(+)-pantoyl lactone crystal in 13～15 ℃, c induces set by step, (3) recrystallization more set by step, detect specific rotatory power, obtain L-(+)-pantoyl lactone; Described system loss amount is gross weight poor of the gross weight of pantoyl lactone solution and step crystal seed that b adds in the step (1) and step c gained xln and mother liquor, i.e. G=G1+G2-G3-G4.
3. fractionation pantoyl lactone according to claim 1 prepares D-(-)-or the method for L-(+)-pantoyl lactone, it is characterized in that: when the crystal seed that adds among the step b is L-(+)-pantoyl lactone crystal, in mother liquor, replenish weight and be G3 pantoyl lactone and with equiponderant water of system loss amount G and/or toluene, be warming up to 30～70 ℃ of dissolvings, then under agitation condition, add 50～100 purpose D-(-)-pantoyl lactone crystal in 13～15 ℃, c induces set by step, (3) recrystallization more set by step, detect specific rotatory power, obtain D-(-)-pantoyl lactone; Described system loss amount is gross weight poor of the gross weight of pantoyl lactone solution and step crystal seed that b adds in the step (1) and step c gained xln and mother liquor, i.e. G=G1+G2-G3-G4.
4. fractionation pantoyl lactone according to claim 1 prepares D-(-)-or the method for L-(+)-pantoyl lactone, and it is characterized in that: the purity of described DL-pantoyl lactone or D-(-)-pantoyl lactone or L-(+)-pantoyl lactone is not less than 96.5%.
5. fractionation pantoyl lactone according to claim 1 prepares D-(-)-or the method for L-(+)-pantoyl lactone, it is characterized in that: described opticity pantoyl lactone is D-(-)-pantoyl lactone and L-(+)-pantoyl lactone inequality blended mixture, perhaps is D-(-)-pantoyl lactone of DL-pantoyl lactone and inequality and L-(+)-pantoyl lactone three's mixture.
6. fractionation pantoyl lactone according to claim 1 prepares D-(-)-or the method for L-(+)-pantoyl lactone, it is characterized in that: in the step (1) be with water and/or toluene as solvent, the mass percent concentration that pantoyl lactone is made into weight under 30～70 ℃ of conditions and is G1 is 76～88% pantoyl lactone solution.
7. prepare D-(-)-or the method for L-(+)-pantoyl lactone according to each described fractionation pantoyl lactone in the claim 1～3, it is characterized in that: the speed of stirring is 20～150 rev/mins.
8. fractionation pantoyl lactone according to claim 1 prepares D-(-)-or the method for L-(+)-pantoyl lactone, it is characterized in that: in the steps d with suction filtration gained xln with after toluene or o-Xylol mix, be warming up to 30～70 ℃ and make the xln dissolving.
9. fractionation pantoyl lactone according to claim 1 prepares D-(-)-or the method for L-(+)-pantoyl lactone, it is characterized in that: with specific rotatory power
For+20 °～+ 30 ° or
Be-30 °～-20 ° xln set by step during the d recrystallization, the mass ratio of xln and toluene or o-Xylol is 4: 1.
10. fractionation pantoyl lactone according to claim 1 prepares D-(-)-or the method for L-(+)-pantoyl lactone, it is characterized in that: with specific rotatory power
Greater than+30 ° or
Set by step during the d recrystallization, the mass ratio of xln and toluene or o-Xylol is 2: 1 less than-30.0 ° xln.
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