α-生育酚和α-生育酚醋酸酯的制备
|
摘要
本文对α-生育酚及α-生育酚醋酸酯的制备工艺进行了研究。α-生育酚的制备包括以含量为52.3%的混合生育酚为原料制备非α-生育酚甲基胺盐以及非α-生育酚甲基胺盐的氢解还原。
通过考察反应温度、反应时间、胺试剂的选择及用量、反应物料的比例及非α-生育酚胺甲基化物的分离精制方法对反应的影响,得到制备非α-生育酚甲基胺盐的工艺条件是:反应温度为80℃,反应时间为40min,胺反应试剂为二甲胺,物料的摩尔比n(混合生育酚):n(二甲胺):n(甲醛)=1:3:3,反应转化率可达98.20%,反应产物胺甲基物用乙酸乙酯萃取后,边搅拌边慢慢滴加磷酸至pH值为4.1,使之生成非α-生育酚甲基胺盐,再冷却到0℃结晶,过滤得到胺盐晶体。
在对非α-生育酚甲基胺盐的氢解还原制备α-生育酚的工艺过程中,采用羟甲基化-还原法相结合,即两个反应一步完成的方法。将胺盐溶解于正庚烷中加入高压釜,以5%的钯炭催化剂为氢解反应的催化剂,用量为胺盐质量的5.0%,对甲苯磺酸为羟甲基化催化剂,用量为胺盐质量的3.4%,加入多聚甲醛用量为胺盐质量的25.1%,在氢气压力2.6MPa,温度170℃下反应2h。反应结束待产物冷却后从高压釜中移出,过滤后经真空旋转蒸发将溶剂除去,得到精制的α-生育酚,非α-生育酚甲基胺盐转化率为99.54%,α-生育酚含量为93.60%,收率为90.58%。
以含量为93.60%的α-生育酚为原料制备α-生育酚醋酸酯,考察了反应时间、反应温度、醋酸酐与α-生育酚的摩尔比及催化剂种类等因素对酯化反应的影响。通过实验,得到制备α-生育酚醋酸酯的优化工艺条件为:醋酸酐与α-生育酚的摩尔比为1.8～2:1,催化剂选用对甲苯磺酸,对甲苯磺酸用量为α-生育酚的0.3%,反应温度为95℃,乙酰化反应时间为1h,得到α-生育酚醋酸酯。在该反应条件下,α-生育酚的转化率可达到99.48%,反应选择性为98.81%,α-生育酚醋酸酯的收率可达到98.30%。
Preparation ofα-tocopherol andα-tocopheryl acetate were studied in this paper. The preparation ofα-tocopherol related to two parts: the preparation of non-α-aminomethylated tocopherol salts and then subjected to hydrogenolysis.
Non-α-aminomethylated tocopherol salts were produced from raw material of 52.3% tocopherols mixture. The following factors were considered in this process: reaction temperature, reaction time, selected of amic reagent, ratio of reactants and the separating method of non-α-aminomethylated tocopherol salts. And the optimal technological conditions were obtained: reaction temperature 80℃, reaction time 40min, amic reagent was dimethylamine, the molar ratio of tocopherols mixture, dimethylamine and formaldehyde were 1:3:3, translation rate was up to 98.20%, then the product was extracted by ethylacetate, and then phosphoric acid was added dropwise with stirring until pH value was 4.1, non-α-aminomethylated tocopherol salts were formed. The solution was heated to reflux, and cooled to 0℃,crystalline products were obtained.
Hydroxymethylation-reduction was combined with aminoalkylation-reduction in the process of hydrogenolysis of non-α-aminomethylated tocopherol salts. Non-α-aminomethylated tocopherol salts was dissolved in n-heptane and charged to an autoclave with 5% Pd/C hydrogenolysis catalyst and hydroxymethylation catalyst toluene-p-sulfonic acid, the quality ratio of Pd/C, toluene-p-sulfonic acid, paraformaldehyde and non-α-aminomethylated tocopherol salts was 5.0:3.4:25.1:100. Hydrogenolysis was carried out at 170℃for 2 hours at 2.6MPa hydrogen pressure. The product was cooled, removed from the autoclave, filtered and the solvent removed under vacuum to yieldα-tocopherol, translation rate of non-α-aminomethylated tocopherol salts was 99.54%, purity ofα-tocopherol was 93.60%, yield was 90.58%.
α-tocopheryl acetate was produced from raw material of 93.6%α-tocopherol, the following factors were considered: reaction time, reaction temperature, the molar ratio of acetate anhydride andα-tocopherol and the kinds of catalyst. The optimal technological conditions were obtained: reaction time was 1h, reaction temperature 95℃,the molar ratio of acetate anhydride andα-tocopherol was 1.8~2:1, the ratio of esterification catalyst toluene-p-sulfonic acid toα-tocopherol was 0.27g/100g, andα-tocopheryl acetate was formed,the reaction translation rate was up to 99.48%, selectivity was 98.81% and the yield 98.30%.
通过考察反应温度、反应时间、胺试剂的选择及用量、反应物料的比例及非α-生育酚胺甲基化物的分离精制方法对反应的影响,得到制备非α-生育酚甲基胺盐的工艺条件是:反应温度为80℃,反应时间为40min,胺反应试剂为二甲胺,物料的摩尔比n(混合生育酚):n(二甲胺):n(甲醛)=1:3:3,反应转化率可达98.20%,反应产物胺甲基物用乙酸乙酯萃取后,边搅拌边慢慢滴加磷酸至pH值为4.1,使之生成非α-生育酚甲基胺盐,再冷却到0℃结晶,过滤得到胺盐晶体。
在对非α-生育酚甲基胺盐的氢解还原制备α-生育酚的工艺过程中,采用羟甲基化-还原法相结合,即两个反应一步完成的方法。将胺盐溶解于正庚烷中加入高压釜,以5%的钯炭催化剂为氢解反应的催化剂,用量为胺盐质量的5.0%,对甲苯磺酸为羟甲基化催化剂,用量为胺盐质量的3.4%,加入多聚甲醛用量为胺盐质量的25.1%,在氢气压力2.6MPa,温度170℃下反应2h。反应结束待产物冷却后从高压釜中移出,过滤后经真空旋转蒸发将溶剂除去,得到精制的α-生育酚,非α-生育酚甲基胺盐转化率为99.54%,α-生育酚含量为93.60%,收率为90.58%。
以含量为93.60%的α-生育酚为原料制备α-生育酚醋酸酯,考察了反应时间、反应温度、醋酸酐与α-生育酚的摩尔比及催化剂种类等因素对酯化反应的影响。通过实验,得到制备α-生育酚醋酸酯的优化工艺条件为:醋酸酐与α-生育酚的摩尔比为1.8～2:1,催化剂选用对甲苯磺酸,对甲苯磺酸用量为α-生育酚的0.3%,反应温度为95℃,乙酰化反应时间为1h,得到α-生育酚醋酸酯。在该反应条件下,α-生育酚的转化率可达到99.48%,反应选择性为98.81%,α-生育酚醋酸酯的收率可达到98.30%。
Preparation ofα-tocopherol andα-tocopheryl acetate were studied in this paper. The preparation ofα-tocopherol related to two parts: the preparation of non-α-aminomethylated tocopherol salts and then subjected to hydrogenolysis.
Non-α-aminomethylated tocopherol salts were produced from raw material of 52.3% tocopherols mixture. The following factors were considered in this process: reaction temperature, reaction time, selected of amic reagent, ratio of reactants and the separating method of non-α-aminomethylated tocopherol salts. And the optimal technological conditions were obtained: reaction temperature 80℃, reaction time 40min, amic reagent was dimethylamine, the molar ratio of tocopherols mixture, dimethylamine and formaldehyde were 1:3:3, translation rate was up to 98.20%, then the product was extracted by ethylacetate, and then phosphoric acid was added dropwise with stirring until pH value was 4.1, non-α-aminomethylated tocopherol salts were formed. The solution was heated to reflux, and cooled to 0℃,crystalline products were obtained.
Hydroxymethylation-reduction was combined with aminoalkylation-reduction in the process of hydrogenolysis of non-α-aminomethylated tocopherol salts. Non-α-aminomethylated tocopherol salts was dissolved in n-heptane and charged to an autoclave with 5% Pd/C hydrogenolysis catalyst and hydroxymethylation catalyst toluene-p-sulfonic acid, the quality ratio of Pd/C, toluene-p-sulfonic acid, paraformaldehyde and non-α-aminomethylated tocopherol salts was 5.0:3.4:25.1:100. Hydrogenolysis was carried out at 170℃for 2 hours at 2.6MPa hydrogen pressure. The product was cooled, removed from the autoclave, filtered and the solvent removed under vacuum to yieldα-tocopherol, translation rate of non-α-aminomethylated tocopherol salts was 99.54%, purity ofα-tocopherol was 93.60%, yield was 90.58%.
α-tocopheryl acetate was produced from raw material of 93.6%α-tocopherol, the following factors were considered: reaction time, reaction temperature, the molar ratio of acetate anhydride andα-tocopherol and the kinds of catalyst. The optimal technological conditions were obtained: reaction time was 1h, reaction temperature 95℃,the molar ratio of acetate anhydride andα-tocopherol was 1.8~2:1, the ratio of esterification catalyst toluene-p-sulfonic acid toα-tocopherol was 0.27g/100g, andα-tocopheryl acetate was formed,the reaction translation rate was up to 99.48%, selectivity was 98.81% and the yield 98.30%.
引文
[1] Hickman, Kenneth C D. Antioxidant[P].US:2349274,1944-05-23.
[2] Hickman,Kenneth C D. Preparation of Stabilized Edible Substances[P].US:2349277,1944- 05-23.
[3] Hickman,Kenneth C D.Preparation of Tocopherol-Containing Materials and Products[P].US: 2349278,1944-05-23.
[4] 彭司勋.药物化学[M].高等教育出版社,1998:215-236.
[5] John Wiley.Kirk-Othmer Encyclopedia of Chemical Technolohy,Third Edition[M].New York, 1980,24:214-225.
[6] 韩国麒,徐学兵,李桂华.生育酚的类型、结构和功能[J].郑州粮食学院学报,1993,1:94-101.
[7] Kamal-Eldin A.,L.Appelqvist.The Chemistry and Antioxidant Properties of Tocopherols and Tocotrienols[J].Lipids,1996,31(7),671-701.
[8] Azzi,A.,A.Stocker.Vitamin E:non-Antioxidant Roles[J].Progress in Lipid Research,2000, 39:231-255.
[9] Burton G W et al.Vitamin E Application of the Principles of Physical Organic Chemistry to the Exploration of the Structure and Function[J].Chem. Res., 1986,19:194-199.
[10] Andrew Weil.Natural and synthetic Vitamin E Sources and Their Biopotency. http:// www. vitamin-e.net.
[11] 邵斌.天然 D-α-生育酚[J].中国食品添加剂,2000,2:78-83.
[12] Gladys Blocketal.Antioxidant Vitamins and Disease Prevention[J].Food Technology, 1994, 7:80-83.
[13] K.U.Ingold, et al.Biokinetics of and Discrimination Between Dietary RRR- and SRR-α- Tocopherols in the Male Rat[J]. Lipids,1987,22:65-172.
[14] 孟紫强,秦国华.维生素的抗诱变性及其机理[J].癌变·畸变·突变,2000,12(4):242-245.
[15] 汪多仁主编.催化剂化学品生产新技术[M].北京:科学技术文献出版社,2001:125-156.
[16] 《 化 工 百 科 全 书 》 编 辑 委 员 会 . 化 工 百 科 全 书 ( 第 16 卷 )[M]. 北 京 : 化 学 工 业 出 版社,1997:747-749.
[17] 朱 圣 东 , 吴 迎 . 天 然 生 育 酚 的 制 备 及 其 在 化 妆 品 中 的 应 用 [J]. 日 用 化 学 工 业 , 2001,31(6):63-64.
[18] 喻敏.加入维生素为个人洁肤品增值[J].日用化学品科学,2000,23(增刊 1):116-117.
[19] 肖雄.生育酚的研究与应用[J].畜牧业,2002,4:24-26.
[20] 宋志刚,王建民,朱立贤.生育酚的研究现状与未来[J].饲料研究,2001,4:15-19.
[21] 宋志刚等,朱立贤.生育酚免疫研究进展[J].饲料博览,2001,2:30-31.
[22] 胡丽.天然生育酚生产现状与应用前景[J].医药化工,2004,11:24-27.
[23] 陈大淦.天然生育酚的提取[J].中国油脂, 1989, 4:33-36.
[24] Foster Charles H.Process for Separation of Tocopherol Homologues(I)[P].US:4602098, 1986-07-22.
[25] Foster Charles H.,Process for Separation of Tocopherol Homologues(II)[P].US:4607111, 1986-08-19.
[26] Foster, Charles H. ,Process for Separation of Tocopherol Homologues[P].US: 4480108, 1984-10-30.
[27] d'Harlingue A et al. Plastid Enzymes of Terpenoid Biosynthesis[J].Biol. Chem., 1985, 260(15):200-203.
[28] Furuya Tsutomu.Process for Production of Tocopherols[P].US: 4978617, 1990-12-18.
[29] Dellapenna Dean,Shintani David K.Transgenic Plants with Tocopherol Methyltransferase [P].WO:9904622,1999-02-04.
[30] Leonard Weisler,Conversion of beta-,gamma-,and delta-Tocopherol to alph-Tocopherol[P]. US:2486539,1949-11-01.
[31] Bruggermann Konrad,Herguijuela Juan Ramon.Hydroxymethylation of Tocopherols[P]. US: 5892058,1999-04-06.
[32] 雷炳福.非 α-生育酚甲基化的研究[D].北京:清华大学,1996.
[33] Baxter James G.. Formylating Tocopherol Material[P]. US: 2592531.1952-04-15.
[34] Lechtken Peter, Hoercher Ulrich. Preparation of d-alpha-Tocopherol from Natural Intermediates[P].US: 4925960,1990-05-15.
[35] The Merck Index,13th ed.[M].New Jersey:Merck&Co. Inc., 2001:9571-9574.
[36] 中华人民共和国卫生部药典委员会.中华人民共和国药典:一九九五年版二部[M].北京:化学工业出版社,广东科技出版社,1995:830-832.
[37] Panin Giorgio.Use of Vitamin E Acetate[P].SI:910367,2004-04-30.
[38] 雷炳福. α-生育酚酯类产品及其制备方法[J].西部粮油科技,2003,2:29-32.
[39] Krill Steffen,Kretz Stephan,Huthmacher.Process for the Production of alpha-Tocopherol Acetate by Condensation of Trimethyldroquinone with Isophytol[P].EP:1132384A2, 2001-12-09.
[40] Rainer Lowack,Joachim Meyer,Manfred Eggersdorfer,Paul Grafer,Preparation of alpha- Tocopherol and alpha-Tocopheryl Acetate in Liquid or Supercritical Carbon Dioxide[P]. US:5523420,1996-06-04.
[41] Bonrath Werner,Dittel Claus,Netscher Thomas,Pabst Thomas,Schmid Rudolf.Manufacture of Tocopheryl Acetate[P].US:2006094886,2006-05-04.
[42] Hong Ki-Sung,Kim Eu-Chung. Precess for Preparing dl-alpha-Tocopherol Acetate[P].KR:9100896,1991-06-04.
[43] Kai-UweBaldenlus,Wulf Kaiser,Bernhard Bockstiegel.Preparation of α-Tocopherol or α- Tocopheryl Acetate by Reacting Trimethylhydroquinone and Phytol or Isophytol,with Recycling of the Zinc Halide Condensation Catalyst[P].US:6005122,1999-12-21.
[44] Bonrath Werner,Cirillo Fabio.Process for the Preparation of Tocol Acylates and Tocopherol Acylates[P].US:2002017451,2002-02-14.
[45] Schulz Bernhard,Renauer Erich.Preparation of Tocol Acylates and Tocopherol Propionate[P]. CA:1173842,1984-09-04.
[46] I.V.Kozhevnikov,S.M.Kulikov,N.G.Chukaeva,A.T.Kirsanov,A.B.Letunova,V.I.Blinova. Syntheses of vitamins E and K1 catalyzed by heteropoly acids[J].React.Kinet.Catal.Lett,1992,47(1):59-64.
[47] Bonrath Werner,Breuninger Manfred,Malalse Gregory,Netscher Thomas.New Route to alpha-Tocopherol,alpha-Tocopheryl Alkanoates and Precursors Thereof[P].US: 2006235234,2006-10-19.
[48] Schulz Bernhard,Renauer Erich. Preparation of Tocopherol Acetate and Tocopheryl Propionate[P]. CA:1173842 1984-09-04.
[49] Werner Bonrath, Claus Dittel, Lisa Giraudi, Thomas Nerscher, Thomas Pabst. Process for the Manufacture of Alpha-Tocopheryl Acetate[P].US:20060052618,2006-03-09.
[50] Bonrath Werner,Breuninger Manfred,Malalse Gregory, Nerscher Thomas.A New Route to alpha-Tocopherol alpha-Tocopheryl Alkanoates and Precursors Thereof[P]. WO2005026181, 2005-03-24.
[51] Krill, Steffen Kretz, Stephan Huthmacher,Klaus. Process to produce alpha-Tocopherol Acetate[P].US:6239294,2001-05-29.
[52] 胡传荣,李洪涛,付晶等.天然生育酚乙酸酯的制备[J].现代食品科技,2005,21(2):85-87.
[53] Bonrath Werner,Giraudi Lisa. Process for the manufacture of tocopheryl acylates[p].WO: 2005103026,2005-11-03.
[54] 雷炳福.我国天然生育酚产业化前景初探[J].中国油脂,2003,38(4):49-51.
[55] 朱圣东,吴迎.我国天然生育酚的生产与开发进展[J].化工进展,2001,11:35-38.
[56] 朱圣东,吴迎.我国天然生育酚工业所面临的挑战[J].中国油脂,2001,26(2):14-16.
[57] 陈新民.生育酚试论[J].中国油脂,1985,5:28-34.
[58] 樊 明 涛 ,吴 守 一 , 马 海 乐 .生 育 酚 测 定 方 法 的 研 究 进 展 [J]. 江 苏 大 学 学 报 (自 然 科 学版),2002,23 (1):54-57.
[59] Vitamin E[S]. The United States Pharmacopeia XXIV,2000:1747-1749.
[60] Tocopherols Concentrate Mixed[S].Food Chemicals Codex,4th ed.,1996:419-420.
[61] QB 2483-2000.中华人民共和国轻工行业标准 食品添加剂 天然生育酚[S].
[62] ISO 9936:1997(E).Animal and vegetable fats and oils-Derermination of tocopherols and tocotrienols contents-Method using high-performance liquid chromatography[S]. Geneve:the International Organization for Standardization,1997.
[63] Pocklington,W.D.,and A.Dieffenbacher.on behalf of Commission on Oils,Fat and Derivatives of International Union of Pure and Applied Chemistry, Determination of Tocopherols and Tocotrienols in Vegetable Oils and Fats by High Performance Liquid Chromatography:Results of a collaborative study and the standardized method[J]. Pure&Appl.Chem., 1988,60(6):877-892.
[64] 李雷,陈文利.高效液相色谱法测定脂溶性维生素的含量[J].化工时刊,2003,17(8):40-42.
[65] 蒋晔,刘红菊,郝晓花.4 种脂溶性维生素的非水反相 HPLC 测定[J].中国医药工业杂志.2005,36(2):93-94.
[66] 刑其毅.徐瑞秋.周政.裴伟伟.基础有机化学[M].北京:高等教育出版社,1994:667.
[67] Maurilio TRAMONTINI,Advances in the Chemistry of Mannich Bases[J].Synthesis,1973: 703-776.
[68] Harry.Heaney,The bimolecular aromatic Mannich reaction[J].Organic Synthesis,V3, 953- 973.
[69] 万正道编著.曼尼希反应和曼尼希碱化学[M].科学出版社,1986:347-366..
[70] 姜麟忠.催化氢化在有机合成中的应用[M].化学工业出版社,1987:4-6.
[71] A.P.G 凯 布 默 , F. 范 兰 特 威 克 . 合 成 有 机 化 学 中 的 氢 化 与 氢 解 [M]. 科 学 出 版社,1981:148-152.
[72] Morris Freifelder.卞觉新,何汝芬,季昌晋译.有机合成中的催化氢化[M].安徽:安徽省化工研究所,1971:96-97.
[2] Hickman,Kenneth C D. Preparation of Stabilized Edible Substances[P].US:2349277,1944- 05-23.
[3] Hickman,Kenneth C D.Preparation of Tocopherol-Containing Materials and Products[P].US: 2349278,1944-05-23.
[4] 彭司勋.药物化学[M].高等教育出版社,1998:215-236.
[5] John Wiley.Kirk-Othmer Encyclopedia of Chemical Technolohy,Third Edition[M].New York, 1980,24:214-225.
[6] 韩国麒,徐学兵,李桂华.生育酚的类型、结构和功能[J].郑州粮食学院学报,1993,1:94-101.
[7] Kamal-Eldin A.,L.Appelqvist.The Chemistry and Antioxidant Properties of Tocopherols and Tocotrienols[J].Lipids,1996,31(7),671-701.
[8] Azzi,A.,A.Stocker.Vitamin E:non-Antioxidant Roles[J].Progress in Lipid Research,2000, 39:231-255.
[9] Burton G W et al.Vitamin E Application of the Principles of Physical Organic Chemistry to the Exploration of the Structure and Function[J].Chem. Res., 1986,19:194-199.
[10] Andrew Weil.Natural and synthetic Vitamin E Sources and Their Biopotency. http:// www. vitamin-e.net.
[11] 邵斌.天然 D-α-生育酚[J].中国食品添加剂,2000,2:78-83.
[12] Gladys Blocketal.Antioxidant Vitamins and Disease Prevention[J].Food Technology, 1994, 7:80-83.
[13] K.U.Ingold, et al.Biokinetics of and Discrimination Between Dietary RRR- and SRR-α- Tocopherols in the Male Rat[J]. Lipids,1987,22:65-172.
[14] 孟紫强,秦国华.维生素的抗诱变性及其机理[J].癌变·畸变·突变,2000,12(4):242-245.
[15] 汪多仁主编.催化剂化学品生产新技术[M].北京:科学技术文献出版社,2001:125-156.
[16] 《 化 工 百 科 全 书 》 编 辑 委 员 会 . 化 工 百 科 全 书 ( 第 16 卷 )[M]. 北 京 : 化 学 工 业 出 版社,1997:747-749.
[17] 朱 圣 东 , 吴 迎 . 天 然 生 育 酚 的 制 备 及 其 在 化 妆 品 中 的 应 用 [J]. 日 用 化 学 工 业 , 2001,31(6):63-64.
[18] 喻敏.加入维生素为个人洁肤品增值[J].日用化学品科学,2000,23(增刊 1):116-117.
[19] 肖雄.生育酚的研究与应用[J].畜牧业,2002,4:24-26.
[20] 宋志刚,王建民,朱立贤.生育酚的研究现状与未来[J].饲料研究,2001,4:15-19.
[21] 宋志刚等,朱立贤.生育酚免疫研究进展[J].饲料博览,2001,2:30-31.
[22] 胡丽.天然生育酚生产现状与应用前景[J].医药化工,2004,11:24-27.
[23] 陈大淦.天然生育酚的提取[J].中国油脂, 1989, 4:33-36.
[24] Foster Charles H.Process for Separation of Tocopherol Homologues(I)[P].US:4602098, 1986-07-22.
[25] Foster Charles H.,Process for Separation of Tocopherol Homologues(II)[P].US:4607111, 1986-08-19.
[26] Foster, Charles H. ,Process for Separation of Tocopherol Homologues[P].US: 4480108, 1984-10-30.
[27] d'Harlingue A et al. Plastid Enzymes of Terpenoid Biosynthesis[J].Biol. Chem., 1985, 260(15):200-203.
[28] Furuya Tsutomu.Process for Production of Tocopherols[P].US: 4978617, 1990-12-18.
[29] Dellapenna Dean,Shintani David K.Transgenic Plants with Tocopherol Methyltransferase [P].WO:9904622,1999-02-04.
[30] Leonard Weisler,Conversion of beta-,gamma-,and delta-Tocopherol to alph-Tocopherol[P]. US:2486539,1949-11-01.
[31] Bruggermann Konrad,Herguijuela Juan Ramon.Hydroxymethylation of Tocopherols[P]. US: 5892058,1999-04-06.
[32] 雷炳福.非 α-生育酚甲基化的研究[D].北京:清华大学,1996.
[33] Baxter James G.. Formylating Tocopherol Material[P]. US: 2592531.1952-04-15.
[34] Lechtken Peter, Hoercher Ulrich. Preparation of d-alpha-Tocopherol from Natural Intermediates[P].US: 4925960,1990-05-15.
[35] The Merck Index,13th ed.[M].New Jersey:Merck&Co. Inc., 2001:9571-9574.
[36] 中华人民共和国卫生部药典委员会.中华人民共和国药典:一九九五年版二部[M].北京:化学工业出版社,广东科技出版社,1995:830-832.
[37] Panin Giorgio.Use of Vitamin E Acetate[P].SI:910367,2004-04-30.
[38] 雷炳福. α-生育酚酯类产品及其制备方法[J].西部粮油科技,2003,2:29-32.
[39] Krill Steffen,Kretz Stephan,Huthmacher.Process for the Production of alpha-Tocopherol Acetate by Condensation of Trimethyldroquinone with Isophytol[P].EP:1132384A2, 2001-12-09.
[40] Rainer Lowack,Joachim Meyer,Manfred Eggersdorfer,Paul Grafer,Preparation of alpha- Tocopherol and alpha-Tocopheryl Acetate in Liquid or Supercritical Carbon Dioxide[P]. US:5523420,1996-06-04.
[41] Bonrath Werner,Dittel Claus,Netscher Thomas,Pabst Thomas,Schmid Rudolf.Manufacture of Tocopheryl Acetate[P].US:2006094886,2006-05-04.
[42] Hong Ki-Sung,Kim Eu-Chung. Precess for Preparing dl-alpha-Tocopherol Acetate[P].KR:9100896,1991-06-04.
[43] Kai-UweBaldenlus,Wulf Kaiser,Bernhard Bockstiegel.Preparation of α-Tocopherol or α- Tocopheryl Acetate by Reacting Trimethylhydroquinone and Phytol or Isophytol,with Recycling of the Zinc Halide Condensation Catalyst[P].US:6005122,1999-12-21.
[44] Bonrath Werner,Cirillo Fabio.Process for the Preparation of Tocol Acylates and Tocopherol Acylates[P].US:2002017451,2002-02-14.
[45] Schulz Bernhard,Renauer Erich.Preparation of Tocol Acylates and Tocopherol Propionate[P]. CA:1173842,1984-09-04.
[46] I.V.Kozhevnikov,S.M.Kulikov,N.G.Chukaeva,A.T.Kirsanov,A.B.Letunova,V.I.Blinova. Syntheses of vitamins E and K1 catalyzed by heteropoly acids[J].React.Kinet.Catal.Lett,1992,47(1):59-64.
[47] Bonrath Werner,Breuninger Manfred,Malalse Gregory,Netscher Thomas.New Route to alpha-Tocopherol,alpha-Tocopheryl Alkanoates and Precursors Thereof[P].US: 2006235234,2006-10-19.
[48] Schulz Bernhard,Renauer Erich. Preparation of Tocopherol Acetate and Tocopheryl Propionate[P]. CA:1173842 1984-09-04.
[49] Werner Bonrath, Claus Dittel, Lisa Giraudi, Thomas Nerscher, Thomas Pabst. Process for the Manufacture of Alpha-Tocopheryl Acetate[P].US:20060052618,2006-03-09.
[50] Bonrath Werner,Breuninger Manfred,Malalse Gregory, Nerscher Thomas.A New Route to alpha-Tocopherol alpha-Tocopheryl Alkanoates and Precursors Thereof[P]. WO2005026181, 2005-03-24.
[51] Krill, Steffen Kretz, Stephan Huthmacher,Klaus. Process to produce alpha-Tocopherol Acetate[P].US:6239294,2001-05-29.
[52] 胡传荣,李洪涛,付晶等.天然生育酚乙酸酯的制备[J].现代食品科技,2005,21(2):85-87.
[53] Bonrath Werner,Giraudi Lisa. Process for the manufacture of tocopheryl acylates[p].WO: 2005103026,2005-11-03.
[54] 雷炳福.我国天然生育酚产业化前景初探[J].中国油脂,2003,38(4):49-51.
[55] 朱圣东,吴迎.我国天然生育酚的生产与开发进展[J].化工进展,2001,11:35-38.
[56] 朱圣东,吴迎.我国天然生育酚工业所面临的挑战[J].中国油脂,2001,26(2):14-16.
[57] 陈新民.生育酚试论[J].中国油脂,1985,5:28-34.
[58] 樊 明 涛 ,吴 守 一 , 马 海 乐 .生 育 酚 测 定 方 法 的 研 究 进 展 [J]. 江 苏 大 学 学 报 (自 然 科 学版),2002,23 (1):54-57.
[59] Vitamin E[S]. The United States Pharmacopeia XXIV,2000:1747-1749.
[60] Tocopherols Concentrate Mixed[S].Food Chemicals Codex,4th ed.,1996:419-420.
[61] QB 2483-2000.中华人民共和国轻工行业标准 食品添加剂 天然生育酚[S].
[62] ISO 9936:1997(E).Animal and vegetable fats and oils-Derermination of tocopherols and tocotrienols contents-Method using high-performance liquid chromatography[S]. Geneve:the International Organization for Standardization,1997.
[63] Pocklington,W.D.,and A.Dieffenbacher.on behalf of Commission on Oils,Fat and Derivatives of International Union of Pure and Applied Chemistry, Determination of Tocopherols and Tocotrienols in Vegetable Oils and Fats by High Performance Liquid Chromatography:Results of a collaborative study and the standardized method[J]. Pure&Appl.Chem., 1988,60(6):877-892.
[64] 李雷,陈文利.高效液相色谱法测定脂溶性维生素的含量[J].化工时刊,2003,17(8):40-42.
[65] 蒋晔,刘红菊,郝晓花.4 种脂溶性维生素的非水反相 HPLC 测定[J].中国医药工业杂志.2005,36(2):93-94.
[66] 刑其毅.徐瑞秋.周政.裴伟伟.基础有机化学[M].北京:高等教育出版社,1994:667.
[67] Maurilio TRAMONTINI,Advances in the Chemistry of Mannich Bases[J].Synthesis,1973: 703-776.
[68] Harry.Heaney,The bimolecular aromatic Mannich reaction[J].Organic Synthesis,V3, 953- 973.
[69] 万正道编著.曼尼希反应和曼尼希碱化学[M].科学出版社,1986:347-366..
[70] 姜麟忠.催化氢化在有机合成中的应用[M].化学工业出版社,1987:4-6.
[71] A.P.G 凯 布 默 , F. 范 兰 特 威 克 . 合 成 有 机 化 学 中 的 氢 化 与 氢 解 [M]. 科 学 出 版社,1981:148-152.
[72] Morris Freifelder.卞觉新,何汝芬,季昌晋译.有机合成中的催化氢化[M].安徽:安徽省化工研究所,1971:96-97.