CN1332164A - 酰化方法 - Google Patents
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- 238000000034 method Methods 0.000 title claims description 26
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- 239000011732 tocopherol Substances 0.000 claims abstract description 33
- 229930003799 tocopherol Natural products 0.000 claims abstract description 32
- 229960001295 tocopherol Drugs 0.000 claims abstract description 31
- 235000010384 tocopherol Nutrition 0.000 claims abstract description 30
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 claims abstract description 30
- DFUSDJMZWQVQSF-XLGIIRLISA-N (2r)-2-methyl-2-[(4r,8r)-4,8,12-trimethyltridecyl]-3,4-dihydrochromen-6-ol Chemical compound OC1=CC=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1 DFUSDJMZWQVQSF-XLGIIRLISA-N 0.000 claims abstract description 12
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 8
- 238000005917 acylation reaction Methods 0.000 claims description 8
- 229940087168 alpha tocopherol Drugs 0.000 claims description 6
- 230000005855 radiation Effects 0.000 claims description 6
- 229960000984 tocofersolan Drugs 0.000 claims description 6
- 239000002076 α-tocopherol Substances 0.000 claims description 6
- ODIGIKRIUKFKHP-UHFFFAOYSA-N (n-propan-2-yloxycarbonylanilino) acetate Chemical compound CC(C)OC(=O)N(OC(C)=O)C1=CC=CC=C1 ODIGIKRIUKFKHP-UHFFFAOYSA-N 0.000 claims description 5
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical group CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 4
- 229940042585 tocopherol acetate Drugs 0.000 description 16
- ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 description 12
- ZAKOWWREFLAJOT-UHFFFAOYSA-N d-alpha-Tocopheryl acetate Natural products CC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-UHFFFAOYSA-N 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 11
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 230000009466 transformation Effects 0.000 description 8
- 230000010933 acylation Effects 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 239000002253 acid Substances 0.000 description 4
- 230000035484 reaction time Effects 0.000 description 4
- 229930003427 Vitamin E Natural products 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000007795 chemical reaction product Substances 0.000 description 3
- 235000019439 ethyl acetate Nutrition 0.000 description 3
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 229940046009 vitamin E Drugs 0.000 description 3
- 239000011709 vitamin E Substances 0.000 description 3
- 235000019165 vitamin E Nutrition 0.000 description 3
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- ZYURHZPYMFLWSH-UHFFFAOYSA-N octacosane Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCCCCC ZYURHZPYMFLWSH-UHFFFAOYSA-N 0.000 description 2
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 125000002640 tocopherol group Chemical class 0.000 description 2
- 235000019149 tocopherols Nutrition 0.000 description 2
- PZZKGQBMBVYPGR-UHFFFAOYSA-N η-tocopherol Chemical compound OC1=C(C)C=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1 PZZKGQBMBVYPGR-UHFFFAOYSA-N 0.000 description 2
- GJJVAFUKOBZPCB-ZGRPYONQSA-N (r)-3,4-dihydro-2-methyl-2-(4,8,12-trimethyl-3,7,11-tridecatrienyl)-2h-1-benzopyran-6-ol Chemical class OC1=CC=C2OC(CC/C=C(C)/CC/C=C(C)/CCC=C(C)C)(C)CCC2=C1 GJJVAFUKOBZPCB-ZGRPYONQSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- -1 acyl anhydrides Chemical class 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 150000007933 aliphatic carboxylic acids Chemical class 0.000 description 1
- 239000005350 fused silica glass Substances 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
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- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 229960003424 phenylacetic acid Drugs 0.000 description 1
- 239000003279 phenylacetic acid Substances 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229930003802 tocotrienol Natural products 0.000 description 1
- 239000011731 tocotrienol Substances 0.000 description 1
- 229940068778 tocotrienols Drugs 0.000 description 1
- 235000019148 tocotrienols Nutrition 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- RZFHLOLGZPDCHJ-XZXLULOTSA-N α-Tocotrienol Chemical compound OC1=C(C)C(C)=C2O[C@@](CC/C=C(C)/CC/C=C(C)/CCC=C(C)C)(C)CCC2=C1C RZFHLOLGZPDCHJ-XZXLULOTSA-N 0.000 description 1
- FGYKUFVNYVMTAM-WAZJVIJMSA-N β-tocotrienol Chemical compound OC1=CC(C)=C2O[C@@](CC/C=C(C)/CC/C=C(C)/CCC=C(C)C)(C)CCC2=C1C FGYKUFVNYVMTAM-WAZJVIJMSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
- C07D311/70—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with two hydrocarbon radicals attached in position 2 and elements other than carbon and hydrogen in position 6
- C07D311/72—3,4-Dihydro derivatives having in position 2 at least one methyl radical and in position 6 one oxygen atom, e.g. tocopherols
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyrane Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cephalosporin Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
母育酚和生育酚可通过用酰化剂和微波处理而被酰化。
Description
本发明涉及一种新型的制备母育酚和生育酚酰化产物的方法。母育酚是化合物2-甲基-2(4，8，12-三甲基-十三烷基)-苯并二氢吡喃-6-酚。这里所用的术语生育酚指的是所有来源于母育酚基本结构并具有维生素E特征的化合物，即：带有饱和(母育酚)侧链的生育酚，如：α-、β-、γ-、δ-、ζ2-和η-生育酚，和侧链上有三个双键的母育三烯酚(tocotrienols)如：ε-和ζ1-生育酚。其中在各种生育酚中，(全部外消旋的)-α-生育酚(通常称作维生素E)是非常值得注意的。
本发明优选是关于一种新型的制备生育酚酰化产物，更优选是生育酚乙酸酯的方法。维生素E主要的商品形式是(全部外消旋的)-α-生育酚乙酸酯。本发明优选是关于一种制备(全部外消旋的)-α-生育酚乙酸酯的方法。但是其它如上述提及的那些生育酚也可通过本发明的方法很容易地酰化。另外，通过本发明的方法，生育酚可以酰化成其外消旋体或单独对映体的形式。
由乙酸酐和(全部外消旋的)-α-生育酚开始，不使用催化剂，让乙酸酐过量来合成(全部外消旋的)-α-生育酚乙酸酯已由Surmatis等的USP 2,723,278报道。在回流条件下三个小时，产物即形成。产率未给出。该反应也可在吡啶作为催化剂存在的条件下室温进行，在三天的反应时间后，得到96％(全部外消旋的)-α-生育酚乙酸酯，见Cohen等的Helv.Chim.Acta 1981，64，1158。
根据本发明，已发现母育酚和生育酚的酰化作用可以在微波的辐射下有利地完成。与现有技术方法相比，本发明的方法需要的反应时间短，所得产率较好并且反应混合物便于加工。特别地，本发明的方法不必要求对反应混合物外部加热，从而对整个反应混合物提供了均匀的反应条件。
因此，本发明涉及的是一种新型的制备母育酚或生育酚酰化产物的方法，该方法包括在用微波辐射的条件下将母育酚或生育酚与酰化剂反应。
这里所用的术语“微波”指的是电磁谱频率为30GHz-300MHz的相应波长为1cm-1m的区域。为了不与雷达的波长(1cm-25cm)相干涉，家用或工业用微波加热器要求在12.2cm(2.45GHz)或33.3cm(918MHz)下操作。因而在本发明一个优选的实施方案中，术语微波特别是指那样的波长。在本发明的方法中，可以使用普通微波设备。适合本发明方法的微波设备由如：MLS公司，Leutkirch，德国(LavisMultiquant 1000)；或MILESTONE公司，Monroe，CT 06468，USA(Ethos反应器)供应。一般实施本发明方法的辐射时施加的辐射功率为大约600-1200W，更优选大约800-大约1000W。
常用于酰化母育酚和生育酚中存在的酚羟基的任何酰化剂都可用来进行酰化作用，如：酰基酐或卤化物。这种酰化剂中的酰基可来源于脂族羧酸，如链烷酸，特别是C1-7链烷酸如乙酸、丙酸、丁酸或新戊酸，或更高级的链烷酸如棕榈酸；或来源于芳族羧酸，如苯甲酸；或芳脂族酸，如苯基乙酸。
可以在存在或不存在催化剂如有机碱，例如吡啶或二甲基氨基吡啶，或有机或无机酸，例如硫酸或对甲苯磺酸的条件下进行酰化作用。有利的是，如果使用催化剂，则选择挥发性催化剂。在本发明一个优选方面中，在无催化剂的条件下进行酰化作用。酰化剂宜过量使用，即相对化学计量所需量过量大约100％。反应适合在惰性气氛下进行。所需的母育酚或生育酚酰化产物可用常规方式从反应产物中分离出来，如减压下加热反应产物以除去过量的酰化剂和催化剂，如果有的话，以及其它不想要的产物。尽管本发明的方法优选是关于(全部外消旋的)-生育酚，特别是(全部外消旋的)-α-生育酚的酰化作用，还要理解为它也可用于酰化旋光对映体，如(d-)-α-生育酚。
本发明通过如下实施例进一步说明。
实施例1：
将(全部外消旋的)-α-生育酚(52.63g，95％纯度，相当于116mmol)和乙酸酐(22.69ml；242mmol)放于一烧瓶中。立即向反应混合物中加入吡啶(0.31ml，3.9mmol)。搅拌反应混合物并在惰性气体(Ar)气氛下用LAVIS Multiquant反应器以800W或1000W的微波辐射。所得反应产物在25mbar下加热至70℃进行纯化。用内标(在100ml正庚烷中的1.0g二十八烷)通过GC(XTI-5，30m×0.32mm，膜0.25mm，熔凝硅石；150℃(0分钟)5℃/分钟335℃(8分钟)，He2.0ml/分钟)分析残余物。5、10、20和30分钟后生育酚转化为其乙酸酯的转化率示于下表1和2中。百分数总和对100的偏离是由于分析误差。
表1：
生育酚向生育酚乙酸酯的转化率；催化剂：吡啶；800W
| 分钟 | 5 | 10 | 20 | 30 |
| 生育酚乙酸酯(％) | 43 | 94 | 99 | 99 |
| 生育酚(％) | 48 | 0 | 0 | 0 |
表2
生育酚向生育酚乙酸酯的转化率；催化剂：吡啶；1000W
| 分钟 | 5 | 10 | 20 | 30 |
| 生育酚乙酸酯(％) | 98 | 98 | 100 | 100 |
| 生育酚(％) | 1 | 0 | 0 | 0 |
当上述反应在普通条件(无辐射，加热到100℃)下进行，30分钟的反应时间后在反应产物中发现了91％的生育酚乙酸酯和0％生育酚。
实施例2：
如实施例1进行生育酚的酰化作用，只是不用催化剂(吡啶)。5、10、20和30分钟后生育酚转化为其乙酸酯的转化率示出下表3和4中。百分数总和对100的偏离是由于分析误差。
表3
生育酚向生育酚乙酸酯的转化率；无催化剂；800W
| 分钟 | 5 | 10 | 20 | 30 |
| 生育酚乙酸酯(％) | 62 | 76 | 97 | 99 |
| 生育酚(％) | 37 | 24 | 3 | 1 |
表4
生育酚向生育酚乙酸酯的转化率；无催化剂；1000W
| 分钟 | 5 | 10 | 20 | 30 |
| 生育酚乙酸酯(％) | 73 | 86 | 98 | 99 |
| 生育酚(％) | 27 | 14 | 2 | 2 |
当上述反应在普通条件(无辐射，无催化剂，回流温度，反应时间3.5小时)下进行时，生育酚转化为其乙酸酯的转化率如下表5所示(百分数总和对100的偏离是由于分析误差)。
表5
生育酚向生育酚乙酸酯的转化率(无催化剂)
| 分钟 | 30 | 60 | 90 | 120 |
| 生育酚乙酸酯(％) | 69 | 93 | 94 | 95 |
| 生育酚(％) | 30 | 9 | 6 | 5 |
Claims (9)
1.制备母育酚和生育酚酰化产物的方法，包括在微波辐射下将母育酚或生育酚与酰化剂反应。
2.权利要求1的方法，其中生育酚被酰化。
3.权利要求2的方法，其中生育酚是(全部外消旋的)-α-生育酚。
4.权利要求1-3中任一项的方法，其中酰化剂是乙酰化剂。
5.权利要求1-4中任一项的方法，其中乙酰化剂是乙酸酐。
6.权利要求1-5中任一项的方法，其中该方法在无催化剂的条件下实施。
7.权利要求1-6中任一项的方法，其中使用的微波源大约600-大约1200W。
8.权利要求1-6中任一项的方法，其中使用的微波源大约800-大约1000W。
9.该新型方法大体上如这里所述，特别参考实施例。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP00114768.5 | 2000-07-10 | ||
| EP00114768 | 2000-07-10 |
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| Publication Number | Publication Date |
|---|---|
| CN1332164A true CN1332164A (zh) | 2002-01-23 |
| CN1200937C CN1200937C (zh) | 2005-05-11 |
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| Application Number | Title | Priority Date | Filing Date |
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| CNB011228237A Expired - Fee Related CN1200937C (zh) | 2000-07-10 | 2001-07-10 | 酰化方法 |
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| Country | Link |
|---|---|
| US (1) | US6444098B2 (zh) |
| JP (1) | JP2002047284A (zh) |
| KR (1) | KR100798506B1 (zh) |
| CN (1) | CN1200937C (zh) |
| AT (1) | ATE296299T1 (zh) |
| BR (1) | BR0102769A (zh) |
| CA (1) | CA2352447A1 (zh) |
| DE (1) | DE60110975T2 (zh) |
| ES (1) | ES2241718T3 (zh) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104016856A (zh) * | 2014-02-21 | 2014-09-03 | 华东理工大学 | 芳香族化合物上的羟基乙酰化的方法 |
| CN105801551A (zh) * | 2014-12-29 | 2016-07-27 | 浙江新和成药业有限公司 | 一种维生素e醋酸酯的清洁生产方法 |
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| EP1689733B1 (en) * | 2003-12-05 | 2008-10-15 | DSM IP Assets B.V. | Process for the manufacture of alkenylated hydroxylated aromatic compounds, of chroman compounds and of their acylated derivatives |
| JP4909534B2 (ja) * | 2005-06-23 | 2012-04-04 | 住友化学株式会社 | ポリエステル及びその製造方法 |
| JP5077908B2 (ja) * | 2006-02-07 | 2012-11-21 | 独立行政法人産業技術総合研究所 | アシル化トコフェロールの製造法 |
| EP2882729B1 (en) * | 2012-08-10 | 2016-09-21 | DSM IP Assets B.V. | Protected tocopherol with reduced content of free tocopherol |
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|---|---|---|---|---|
| US2723278A (en) | 1954-01-25 | 1955-11-08 | Hoffmann La Roche | Preparation of alpha-tocopherol |
| FR2666581B1 (fr) | 1990-09-06 | 1993-05-28 | Rhone Poulenc Nutrition Animal | Procede de preparation d'acetate de tocopherol. |
| JPH06145200A (ja) * | 1992-09-11 | 1994-05-24 | Maruha Corp | アシル化ゼラチンの製造方法 |
| CN1211243A (zh) | 1996-01-29 | 1999-03-17 | Basf公司 | dl－α－生育酚或乙酸dl－α－生育酚酯的制备 |
| FR2760744B1 (fr) | 1997-03-12 | 1999-04-23 | Rhodia Chimie Sa | Procede d'acylation d'un compose aromatique |
| KR100408991B1 (ko) * | 2000-03-23 | 2003-12-11 | 에스케이 주식회사 | ＤＬ-α-토코페롤 아세테이트의 제조방법 |
-
2001
- 2001-07-02 AT AT01116014T patent/ATE296299T1/de not_active IP Right Cessation
- 2001-07-02 ES ES01116014T patent/ES2241718T3/es not_active Expired - Lifetime
- 2001-07-02 DE DE60110975T patent/DE60110975T2/de not_active Expired - Lifetime
- 2001-07-05 CA CA002352447A patent/CA2352447A1/en not_active Abandoned
- 2001-07-06 BR BR0102769-7A patent/BR0102769A/pt not_active Application Discontinuation
- 2001-07-09 JP JP2001207414A patent/JP2002047284A/ja not_active Withdrawn
- 2001-07-09 US US09/900,587 patent/US6444098B2/en not_active Expired - Fee Related
- 2001-07-10 KR KR1020010041096A patent/KR100798506B1/ko not_active IP Right Cessation
- 2001-07-10 CN CNB011228237A patent/CN1200937C/zh not_active Expired - Fee Related
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104016856A (zh) * | 2014-02-21 | 2014-09-03 | 华东理工大学 | 芳香族化合物上的羟基乙酰化的方法 |
| CN105801551A (zh) * | 2014-12-29 | 2016-07-27 | 浙江新和成药业有限公司 | 一种维生素e醋酸酯的清洁生产方法 |
| CN105801551B (zh) * | 2014-12-29 | 2018-11-30 | 浙江新和成药业有限公司 | 一种维生素e醋酸酯的清洁生产方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| KR20020005510A (ko) | 2002-01-17 |
| JP2002047284A (ja) | 2002-02-12 |
| CA2352447A1 (en) | 2002-01-10 |
| KR100798506B1 (ko) | 2008-01-28 |
| US20020017451A1 (en) | 2002-02-14 |
| BR0102769A (pt) | 2002-02-26 |
| CN1200937C (zh) | 2005-05-11 |
| ES2241718T3 (es) | 2005-11-01 |
| US6444098B2 (en) | 2002-09-03 |
| DE60110975D1 (de) | 2005-06-30 |
| DE60110975T2 (de) | 2005-10-27 |
| ATE296299T1 (de) | 2005-06-15 |
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