CN103360438B - A kind of preparation method of pair of propylidene thio glycoside compound - Google Patents
A kind of preparation method of pair of propylidene thio glycoside compound Download PDFInfo
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Abstract
The present invention relates to hydroxyl protection technical field in chemosynthesis, particularly to the preparation method of a kind of pair of propylidene thio glycoside compound: solvent is adjusted temperature to 10 DEG C 15 DEG C；Adding zinc chloride and the raw material of hydroxyl to be protected in solvent, add phosphoric acid and 2,2 dimethoxy propanes, stirring, room temperature reaction, HPLC detects without raw material peak, obtains reactant liquor, through post processing, to obtain final product.The method of the present invention carries out propylidene reaction to thiogalactoside compound, and reaction condition is gentle, and method therefor is easily operated, time saving and energy saving, and the response time is short, easily operates；This method improves productivity, and meanwhile, experimental implementation and post processing are simpler, the easy crystallize of product, and purity is high, all can reach more than 98%, and effect is notable, can be suitably used for large-scale production.
Description
Technical field
The present invention relates to hydroxyl protection technical field in chemosynthesis, particularly to the preparation method of a kind of pair of propylidene thio glycoside compound.
Background technology
The most frequently used hydroxyl protecting group mainly has a three major types: esters, ethers and acetal or ketal class; on sugar ring the guard method of adjacent two hydroxyls be usually by double for hydroxyl propylidene; usually use acetone as alcoholic extract hydroxyl group protective agent; anhydrous zinc chloride is catalyst, and sulphuric acid is dehydrant, and this method process is loaded down with trivial details; yield is low; response time is long, is typically necessary 18-36 hour, is not suitable for industrialized production.
Zhang Weihong etc. in " chemical industry and engineering ", 2005, vol.22; in No2 " 1; the synthesis of 2-oxygen-isopropylidene-α-D-glucofuranose " in report to D-Glucose hydroxyl protection use acetone, the phosphoric acid of 85%, zinc chloride; need room temperature reaction 30 hours; prepare 1,2,5; 6-oxygen-diisopropyl fork base-α-D-glucofuranose, productivity is only 53.6%.
Wu Lihong etc. are at " fine and specialty chemicals ", 2006, Vol 14, the amount ratio reporting the optimisation substance being prepared diisopropylidene-D-mannitol by D-mannitol and acetone in " Synthesis of Diisopropylidene-D-mannitol Catalyzed by Zinc Chloride " in No1 is: n (PEARLITOL 25C): n (acetone): n (zinc chloride)=1:21.4:1.85, suitable reaction temperature is 30-35 DEG C, response time is 12h, and productivity is 62.8 %.
Double propylidene hydroxyl protection response time disclosed in above-mentioned two documents are long, and yield is low.
Summary of the invention
Long in order to solve the response time present in the double propylidene process of above hydroxyl, that yield is low problem, the invention provides the preparation method of double propylidene thio glycoside compounds that a kind of response time is short, yield is high.
The present invention is obtained through the following steps:
The preparation method of a kind of pair of propylidene thio glycoside compound, comprises the following steps:
(1) solvent is adjusted temperature to 10 DEG C-15 DEG C；
(2) adding zinc chloride and the raw material of hydroxyl to be protected in solvent, add phosphoric acid and 2,2-dimethoxypropane, stirring, room temperature reaction, HPLC detects without raw material peak, obtains reactant liquor, through post processing, to obtain final product.
The raw molecule formula of described hydroxyl to be protected is:
R therein can be the substituent groups such as methyl, ethyl, phenyl ring, and reaction equation is:
The raw material of described hydroxyl to be protected is ethyl-2,3,4,6-tetrahydroxy-β-D-sulfur galactopyranoside.
Described preparation method, zinc chloride is 0.82-1.48:1 with the mol ratio of the raw material of hydroxyl to be protected.
Described preparation method, phosphoric acid is 3.87-5.2:1 with the mol ratio of the raw material of hydroxyl to be protected.
Described preparation method, 2,2-dimethoxypropane is 1.82-2.54:1 with the mol ratio of the raw material of hydroxyl to be protected.
Described preparation method, described solvent is acetone or dichloromethane.
Described preparation method, solvent is 8-11:1 with the mass ratio of the raw material of hydroxyl to be protected.
Described preparation method, described post processing is for extracting with reactant liquor, addition water and organic solvent with in alkali, and the concentrating under reduced pressure solvent at 40 ~ 50 DEG C of the organic facies after extraction, to dry, to obtain final product.
Described preparation method, described organic solvent is dichloromethane or ethyl acetate.
Described preparation method, described alkali is sodium carbonate liquor or the sodium bicarbonate solution of 25% of 25%.
Beneficial effects of the present invention:
The method of the present invention carries out propylidene reaction to thiogalactoside compound, and reaction condition is gentle, and method therefor is easily operated, time saving and energy saving, and the response time is short, easily operates；This method improves productivity, and meanwhile, experimental implementation and post processing are simpler, the easy crystallize of product, and purity is high, all can reach more than 98%, and effect is notable, can be suitably used for large-scale production.
Accompanying drawing explanation
Accompanying drawing 1 is the nuclear magnetic spectrogram carbon spectrum of the product that the embodiment of the present invention 1 obtains,
Accompanying drawing 2 is the nuclear magnetic spectrogram hydrogen spectrum of the product that embodiment 1 obtains.
Detailed description of the invention
Embodiment
1
:
Take 100ml(80g) acetone soln, be cooled to 10 DEG C, add 5g(0.0367mol) zinc chloride, stirring, add 8g(0.0357mol) and ethyl-2,3,4,6-tetrahydroxy-β-D-sulfur galactopyranosides；It is then slowly added into the phosphatase 11 0ml(0.172mol of 85%)；Add 10ml(0.081mol) 2,2 ,-dimethoxy propane, stirring reaction 4h.Adding sodium carbonate liquor cancellation, extraction after having reacted, separate organic facies, solvent evaporated, obtain grease 10.8g, obtain pure products 8.3g after crystallize, purity 99%, productivity is about 88%.
Reaction equation is as follows:
Embodiment
2
:
Take 50ml acetone (40g) solution, be cooled to 10 DEG C, add 3g(0.022mol) zinc chloride, stirring, add 5g(0.0222) and ethyl-2,3,4,6-tetrahydroxy-β-D-sulfur galactopyranosides；It is then slowly added into the phosphoric acid 5ml(0.086mol of 85%)；Add 6ml (0.0488mol) 2,2 ,-dimethoxy propane, stirring reaction 6h.Adding sodium carbonate liquor cancellation, extraction after having reacted, separate organic facies, solvent evaporated, obtain grease 6.7g, obtain pure products 5.4g after crystallize, purity 98.7%, productivity is about 91%.
Embodiment
3
:
Take 200ml acetone (160g) solution, be cooled to 10 DEG C, add 12g(0.088mol) zinc chloride, stirring, add 15g(0.067mol) and ethyl-2,3,4,6-tetrahydroxy-β-D-sulfur galactopyranosides；It is then slowly added into the phosphoric acid 20ml(0.345mol of 85%)；Add 16ml(0.13mol) 2,2 ,-dimethoxy propane, stirring reaction 3.5 h.Adding sodium carbonate liquor cancellation, extraction after having reacted, separate organic facies, solvent evaporated, obtain grease 21.4g, obtain pure products 15.8g after crystallize, purity 98.5%, productivity is about 89%.
Comparative example
1
:
Take 200ml acetone (160g) solution, be cooled to 10 DEG C, add 12g(0.088mol) zinc chloride, stirring, add 15g(0.067 mol) and ethyl-2,3,4,6-tetrahydroxy-β-D-sulfur galactopyranosides；It is then slowly added into the phosphoric acid 20ml(0.345mol of 85%), stirring reaction 24h.Add sodium carbonate liquor cancellation, extraction after having reacted, separate organic facies, solvent evaporated, obtain grease 15g(product assay 44%), obtain pure products 6.75g after crystallize, purity 98%, productivity is about 37%.
Embodiment
4
:
Take 50ml acetone (40g) solution, be cooled to 10 DEG C, add 5g(0.037mol) zinc chloride, stirring, add 8g(0.029mol) and phenyl-2,3,4,6-tetrahydroxy-β-D-sulfur galactopyranosides；It is then slowly added into the phosphoric acid 7ml(0.12mol of 85%)；Add 6ml (0.0488mol) 2,2 ,-dimethoxy propane, stirring reaction 6h.Adding sodium carbonate liquor cancellation, extraction after having reacted, separate organic facies, solvent evaporated, obtain grease 10g, obtain pure products 8.42g after crystallize, purity 98%, productivity is about 89.7%.
Claims (6)
1. a preparation method for double propylidene thio glycoside compounds, is characterized in that comprising the following steps:
(1) solvent is adjusted temperature to 10 DEG C-15 DEG C；
(2) adding zinc chloride and the raw material of hydroxyl to be protected in solvent, add phosphoric acid and 2,2-dimethoxypropane, stirring, room temperature reaction, HPLC detects without raw material peak, obtains reactant liquor, through post processing, to obtain final product；
The raw molecule formula of described hydroxyl to be protected is:
Wherein, R is methyl, ethyl, benzene ring substitution group；
Zinc chloride is 0.82-1.48:1 with the mol ratio of the raw material of hydroxyl to be protected；
Phosphoric acid is 3.87-5.2:1 with the mol ratio of the raw material of hydroxyl to be protected；
2,2-dimethoxy propane is 1.82-2.54:1 with the mol ratio of the raw material of hydroxyl to be protected.
Preparation method the most according to claim 1, is characterized in that the raw material of described hydroxyl to be protected is ethyl-2,3,4,6-tetrahydroxy-β-D-sulfur galactopyranosides.
Preparation method the most according to claim 1, is characterized in that described solvent is acetone or dichloromethane, and solvent is 8-11:1 with the mass ratio of the raw material of hydroxyl to be protected.
4. according to the preparation method according to any one of claim 1-3, it is characterized in that described post processing extracts with reactant liquor, addition water and organic solvent for using in alkali, the concentrating under reduced pressure solvent at 40 ~ 50 DEG C of the organic facies after extraction, to dry, to obtain final product.
Preparation method the most according to claim 4, is characterized in that described organic solvent is dichloromethane or ethyl acetate.
Preparation method the most according to claim 4, is characterized in that sodium carbonate liquor or the sodium bicarbonate solution of 25% that described alkali is 25%.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4092331A (en) * | 1975-12-30 | 1978-05-30 | S.A. Texaco Belgium N.V. | Preparation of ketone acetals |
| US5747463A (en) * | 1995-11-13 | 1998-05-05 | Bristol-Myers Squibb Company | Malonate derivatives of glycolipids as cell adhesion inhibitors |
| WO2006108903A1 (en) * | 2005-04-13 | 2006-10-19 | Consejo Superior De Investigaciones Científicas | Phosphinite thioglycosides, preparation method and use thereof as novel ligands in asymmetric catalysis |
| CN101157601A (en) * | 2007-11-12 | 2008-04-09 | 浙江理工大学 | Method for synthesizing 2,2-dimethoxypropane |
-
2013
- 2013-07-30 CN CN201310324636.7A patent/CN103360438B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4092331A (en) * | 1975-12-30 | 1978-05-30 | S.A. Texaco Belgium N.V. | Preparation of ketone acetals |
| US5747463A (en) * | 1995-11-13 | 1998-05-05 | Bristol-Myers Squibb Company | Malonate derivatives of glycolipids as cell adhesion inhibitors |
| WO2006108903A1 (en) * | 2005-04-13 | 2006-10-19 | Consejo Superior De Investigaciones Científicas | Phosphinite thioglycosides, preparation method and use thereof as novel ligands in asymmetric catalysis |
| CN101157601A (en) * | 2007-11-12 | 2008-04-09 | 浙江理工大学 | Method for synthesizing 2,2-dimethoxypropane |
Non-Patent Citations (2)
| Title |
|---|
| 1,2-氧-异丙叉基-α-D-呋喃葡萄糖的合成;张卫红等;《化学工业与工程》;20050331;第22卷(第2期);92-95页 * |
| Synthesis of a di-, tri-, and tetrasaccharide unit of the group B streptococcal common antigen;Pozsgay, Vince和Jennings, Harold J.;《Carbohydrate Research》;19881231;第179卷;61-75页 * |
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