CN1800193A - 2-deoxidized glucose preparation method - Google Patents
2-deoxidized glucose preparation method Download PDFInfo
- Publication number
- CN1800193A CN1800193A CN 200510122912 CN200510122912A CN1800193A CN 1800193 A CN1800193 A CN 1800193A CN 200510122912 CN200510122912 CN 200510122912 CN 200510122912 A CN200510122912 A CN 200510122912A CN 1800193 A CN1800193 A CN 1800193A
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- Prior art keywords
- deoxyglucose
- glucal
- add
- reaction
- preparation
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- 238000002360 preparation method Methods 0.000 title claims description 14
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 title 1
- 239000008103 glucose Substances 0.000 title 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 33
- VRYALKFFQXWPIH-PBXRRBTRSA-N (3r,4s,5r)-3,4,5,6-tetrahydroxyhexanal Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)CC=O VRYALKFFQXWPIH-PBXRRBTRSA-N 0.000 claims abstract description 25
- PMMURAAUARKVCB-UHFFFAOYSA-N alpha-D-ara-dHexp Natural products OCC1OC(O)CC(O)C1O PMMURAAUARKVCB-UHFFFAOYSA-N 0.000 claims abstract description 25
- 238000000034 method Methods 0.000 claims abstract description 7
- 238000001953 recrystallisation Methods 0.000 claims abstract description 5
- YVECGMZCTULTIS-PBXRRBTRSA-N glucal Chemical compound OC[C@H]1OC=C[C@@H](O)[C@@H]1O YVECGMZCTULTIS-PBXRRBTRSA-N 0.000 claims description 27
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 18
- 238000006243 chemical reaction Methods 0.000 claims description 17
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- 239000012043 crude product Substances 0.000 claims description 11
- 238000003756 stirring Methods 0.000 claims description 10
- 238000009413 insulation Methods 0.000 claims description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 8
- 239000000047 product Substances 0.000 claims description 7
- 238000001816 cooling Methods 0.000 claims description 6
- 238000004821 distillation Methods 0.000 claims description 6
- 238000007710 freezing Methods 0.000 claims description 6
- 230000008014 freezing Effects 0.000 claims description 6
- 238000006386 neutralization reaction Methods 0.000 claims description 6
- 238000001914 filtration Methods 0.000 claims description 5
- 238000010438 heat treatment Methods 0.000 claims description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- 239000003153 chemical reaction reagent Substances 0.000 claims description 4
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 235000017550 sodium carbonate Nutrition 0.000 claims description 2
- 230000000694 effects Effects 0.000 abstract description 2
- FWFGVMYFCODZRD-UHFFFAOYSA-N oxidanium;hydrogen sulfate Chemical compound O.OS(O)(=O)=O FWFGVMYFCODZRD-UHFFFAOYSA-N 0.000 abstract description 2
- 230000003301 hydrolyzing effect Effects 0.000 abstract 1
- 238000005292 vacuum distillation Methods 0.000 abstract 1
- 238000002425 crystallisation Methods 0.000 description 5
- 230000008025 crystallization Effects 0.000 description 5
- 238000010189 synthetic method Methods 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 2
- 239000012266 salt solution Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 229910052788 barium Inorganic materials 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- 159000000009 barium salts Chemical class 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Landscapes
- Saccharide Compounds (AREA)
Abstract
The invention discloses a method for preparing for 2-deoxyglucose. The method uses D-acetylated dextroglucose and the absolute methanol to obtain the D-gluglucosan on the accelerating effect, and then it dose vacuum distillation to evaporate to dryness the methanol, it adds sulfuric acid water solution on the reacting machine to obtain the 2-deoxyglucose by hydrolyzing, it then uses normal method to do re-crystallization to the course product to obtain the 2-deoxyglucose product.
Description
One, technical field
The present invention relates to a kind of preparation method of organic compound, specifically relate to the preparation method of 2-deoxyglucose.
Two, background technology
Preparation method at present known 2-deoxyglucose has a lot; on U.S. chemical abstract (CA), can retrieve more than ten kinds; IN187908 goes on foot and obtains 2-deoxyglucose (I) through transesterify, hydrolysis two promptly from D-acetylated glucal (II):
This synthetic method is simple to operate, and cost is also lower, but has used the bigger heavy metal barium of toxicity, and second small step in the first step can be streamlined any further.
The synthetic method of latest report (PCT Int.Appl., 2004058786,15 Jul 2004) is from glucal, goes on foot through three and obtains the 2-deoxyglucose.
Though the product purity that this synthetic method obtains is higher, and is more loaded down with trivial details, cost is very high, is not suitable for scale operation and popularization.
Three, summary of the invention
The objective of the invention is to solve big, the shortcomings such as reaction process is loaded down with trivial details, cost height of toxicity that exist among the preparation method of existing 2-deoxyglucose, we provide the method for simple and effective Synthetic 2-deoxyglucose that a kind of toxicity is little, reaction process is simple, cost is low.
A kind of method for preparing the 2-deoxyglucose, its preparation process is as follows:
(1) at first in a reactor, adds D-acetylated glucal (II) and anhydrous methanol, after the stirring and dissolving, slowly add sodium Metal 99.5, generate sodium methylate, generate D-glucal (III) then under the katalysis of sodium methylate, distillation is the methyl alcohol evaporate to dryness, and is standby;
(2) in No. two reactors, add water then, add the vitriol oil, stir also cooling, in the reactor of aqueous sulfuric acid suction in No. two reactors, stir and insulation after, add the reagent neutralization, freezing, centrifugal, dry 2-deoxyglucose crude product;
(3) the crude product recrystallization is got finished product: promptly get crude product and add in another reactor, add dehydrated alcohol, heating for dissolving, the cooling, add the gac press filtration to reactor, cool off, dry 2-deoxyglucose finished product.
Its chemical equation is as follows:
In the reaction that generates D-glucal (III); D-acetylated glucal and anhydrous methanol, mole ratio be 1: 20-1: 100; with the mole ratio of sodium methylate be 1: 0.005-1: 0.05; the preferred mole ratio of D-acetylated glucal and anhydrous methanol, sodium methylate is 1: 56: 0.02; sodium methylate can be bought commercially available, but preferably existing with now doing.
In the reaction that generates 2-deoxyglucose (I); the volumetric molar concentration of the vitriol oil can be from 0.01M-2M; but temperature will be accordingly from high to low (50 ℃--5 ℃); the consumption of aqueous sulfuric acid is decided with the D-acetylated glucal; its mole ratio can be 150: 1-75: 1, and preferably mole ratio is 100: 1.
In the reaction that generates D-glucal (III), temperature of reaction is 20 ℃-65 ℃, reaction times 24-4 hour, adopts higher temperature of reaction to shorten the reaction times accordingly.
In the reaction that generates 2-deoxyglucose (I), if adopt higher vitriolic concentration, its temperature of reaction should be below 5 ℃.
In the aftertreatment that generates D-glucal (III), the used reagent of neutralization reaction is sodium hydroxide or yellow soda ash, is preferably sodium hydroxide, and PH is controlled between 6.8～7.3, in and the time temperature can not surpass temperature of reaction.
The recrystallization of producing crude product and crude product from reaction solution all adopts conventional method, but two-step crystallization must be as cold as below-5 ℃ and keep 24 hours.
Preparation method of the present invention had both saved the process of separation of intermediates D-glucal (III), had avoided more highly toxic barium salt again, had both reduced and had produced this, had improved quality product and yield again, and its yield reaches 71.4%, and is suitable for large-scale industrial production.
Four, embodiment
Come further to understand characteristics of the present invention and effect with the following Examples:
In the 500L reactor, add 60kg D-acetylated glucal, anhydrous methanol 400L, stirring and dissolving slowly adds the 400g sodium Metal 99.5, and reacting liquid pH value is about about 10, and control reaction temperature was 25 ℃ of insulations 12 hours.Insulation finishes, and opens the vacuum pump underpressure distillation, adds entry 400kg in another 500L reactor, vitriol oil 10kg, stir logical cool brine cooling, cool the temperature to 0 ℃, the distillation of 500L reactor finishes, get the D-glucal, material vacuum in the 500L reactor is drawn in the 500L reactor of sulfuric acid water, stirs insulation 12 hours, temperature is controlled at insulation end between-2～5 ℃, the neutralization of hydro-oxidation sodium is about adjust pH to 7.0.Neutralization finishes, and adds gac 10KG, is warming up to 70 ℃ of insulations 2 hours, and insulation finishes, press filtration is to the 500L reactor, and vacuum pump is driven in vacuum distilling, heats up to stir distillation, temperature in the kettle is controlled at 70 ℃, and distillation finishes, and is cooled to 50 ℃, adds dehydrated alcohol 200L heating for dissolving.Temperature rises to boiling reflux, and insulation is to molten entirely, adds gac 5kg after molten entirely.Be incubated 1 hour, cold slightly, press filtration is to crystallization kettle, and it is freezing to feed icy salt solution in the crystallization kettle chuck, temperature control-5 ℃, freezing 24 hours, with centrifugal refrigerated material, dry 28KG2-deoxyglucose crude product.
Get crude product and put into the 500L stainless steel cauldron, add dehydrated alcohol 200L, heating for dissolving, it is transparent that solution is, about 50 ℃ of water cooling temperature.Add gac 3KG, be heated to backflow.Stop heating, cold slightly, press filtration is to crystallization kettle.Crystallization kettle chuck feeding icy salt solution is freezing, and-5 ℃, freezing 24 hours centrifugal, and oven dry gets 23KG2-deoxyglucose finished product, yield 71.4%.
Claims (6)
1, a kind of method for preparing the 2-deoxyglucose, its preparation process is as follows:
(1) at first in a reactor, adds D-acetylated glucal (II) and anhydrous methanol, after the stirring and dissolving, slowly add sodium Metal 99.5, generate sodium methylate, generate D-glucal (III) then under the katalysis of sodium methylate, distillation is the methyl alcohol evaporate to dryness, and is standby;
(2) in No. two reactors, add water then, add the vitriol oil, stir also cooling, in the reactor of aqueous sulfuric acid suction in No. two reactors, stir and insulation after, add the reagent neutralization, freezing, centrifugal, dry 2-deoxyglucose crude product;
(3) the crude product recrystallization is got finished product: promptly get crude product and add in another reactor, add dehydrated alcohol, heating for dissolving, the cooling, add the gac press filtration to reactor, cool off, dry 2-deoxyglucose finished product.
Its chemical equation is as follows:
2, the preparation method of 2-deoxyglucose according to claim 1; it is characterized in that generating in the reaction of D-glucal (III) in step (1); D-acetylated glucal (II) is 1 with the mole ratio of anhydrous methanol: 20-1: 100; with the mole ratio of sodium methylate be 1: 0.005-1: 0.05, D-acetylated glucal II and anhydrous methanol, the preferred mole ratio of sodium methylate are 1: 56-0.02.
3, the preparation method of 2-deoxyglucose according to claim 1 is characterized in that generating in D-glucal (III) reaction in step (1), and temperature of reaction is 20 ℃-65 ℃, reaction times 24-4 hour.
4, the preparation method of 2-deoxyglucose according to claim 1; it is characterized in that generating in the reaction of 2-deoxyglucose (I) in step (2); the volumetric molar concentration of the vitriol oil is 0.01M-2M; temperature of reaction is 50 ℃～-5 ℃; the mole ratio of the consumption of aqueous sulfuric acid and D-acetylated glucal is 150: 1-75: 1, and preferred mole ratio is 100: 1.
5, the preparation method of 2-deoxyglucose according to claim 1 is characterized in that the neutralization reagent described in the step (2) is sodium hydroxide or yellow soda ash, is preferably sodium hydroxide, regulates PH between 6.8-7.3.
6, the preparation method of 2-deoxyglucose according to claim 1, the recrystallization temperature that it is characterized in that the 2-deoxyglucose crude product described in the step (3) is below-5 ℃, and keeps 24 hours.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005101229127A CN100362009C (en) | 2005-12-07 | 2005-12-07 | 2-deoxidized glucose preparation method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005101229127A CN100362009C (en) | 2005-12-07 | 2005-12-07 | 2-deoxidized glucose preparation method |
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| Publication Number | Publication Date |
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| CN1800193A true CN1800193A (en) | 2006-07-12 |
| CN100362009C CN100362009C (en) | 2008-01-16 |
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| Application Number | Title | Priority Date | Filing Date |
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| CNB2005101229127A Expired - Fee Related CN100362009C (en) | 2005-12-07 | 2005-12-07 | 2-deoxidized glucose preparation method |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100579973C (en) * | 2007-02-13 | 2010-01-13 | 中国科学院成都生物研究所 | A kind of preparation method of glucal |
| CN102180914A (en) * | 2011-04-06 | 2011-09-14 | 华东师范大学 | Preparation method of 2-deoxidizing-D-glucose |
| CN102924540A (en) * | 2012-10-22 | 2013-02-13 | 山东鲁抗舍里乐药业有限公司 | Preparation method of 2-deoxy-D-glucose |
| CN102993242A (en) * | 2012-12-05 | 2013-03-27 | 国家海洋局第三海洋研究所 | Preparation process of marine organism source 2-deoxyglucose |
| CN103694279A (en) * | 2013-12-23 | 2014-04-02 | 江西苏克尔新材料有限公司 | Preparation method of 2-deoxy-L-ribose |
| CN105330704A (en) * | 2015-11-13 | 2016-02-17 | 天津现代职业技术学院 | Preparation method of 2-deoxy-D-glucose |
| CN115745934A (en) * | 2022-12-06 | 2023-03-07 | 北京瑞博奥医药科技有限公司 | Preparation method of 1-deuterated-2-deoxy-D-glucose |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6353095B1 (en) * | 1991-09-20 | 2002-03-05 | The Scripps Research Institute | Ketoaldonic acids having formed stereogenic centers of R configuration: methods and compositions |
-
2005
- 2005-12-07 CN CNB2005101229127A patent/CN100362009C/en not_active Expired - Fee Related
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100579973C (en) * | 2007-02-13 | 2010-01-13 | 中国科学院成都生物研究所 | A kind of preparation method of glucal |
| CN102180914A (en) * | 2011-04-06 | 2011-09-14 | 华东师范大学 | Preparation method of 2-deoxidizing-D-glucose |
| CN102924540A (en) * | 2012-10-22 | 2013-02-13 | 山东鲁抗舍里乐药业有限公司 | Preparation method of 2-deoxy-D-glucose |
| CN102924540B (en) * | 2012-10-22 | 2015-12-16 | 山东鲁抗舍里乐药业有限公司 | A kind of preparation method of 2-deoxy-D-glucose |
| CN102993242A (en) * | 2012-12-05 | 2013-03-27 | 国家海洋局第三海洋研究所 | Preparation process of marine organism source 2-deoxyglucose |
| CN103694279A (en) * | 2013-12-23 | 2014-04-02 | 江西苏克尔新材料有限公司 | Preparation method of 2-deoxy-L-ribose |
| CN103694279B (en) * | 2013-12-23 | 2015-12-02 | 江西苏克尔新材料有限公司 | A kind of method preparing 2-deoxidation-L-ribose |
| CN105330704A (en) * | 2015-11-13 | 2016-02-17 | 天津现代职业技术学院 | Preparation method of 2-deoxy-D-glucose |
| CN105330704B (en) * | 2015-11-13 | 2019-05-10 | 天津现代职业技术学院 | The preparation method of 2-deoxy-D-glucose |
| CN115745934A (en) * | 2022-12-06 | 2023-03-07 | 北京瑞博奥医药科技有限公司 | Preparation method of 1-deuterated-2-deoxy-D-glucose |
| CN115745934B (en) * | 2022-12-06 | 2024-12-13 | 北京瑞博奥医药科技有限公司 | A preparation method of 1-deuterated-2-deoxy-D-glucose |
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| CN100362009C (en) | 2008-01-16 |
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Effective date of registration: 20081128 Address after: No. 8, phoenix garden, Longfeng garden, Longjiang District, Gulou District, Jiangsu, Nanjing 501, China Patentee after: Zhu Shuhan Address before: Room 1602, Tian An International Building, No. 122, Zhongshan South Road, Nanjing, Jiangsu Patentee before: Jiangsu Hanfa Trade Development Co., Ltd. |
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