ca(clo)2体系催化氧化甲苷合成葡萄糖醛酸及其内酯

ca(clo)2体系催化氧化甲苷合成葡萄糖醛酸及其内酯 分类号 TQ463 学校编号 10490UDC 密 级 武汉工程大学 硕士学位论文 TEMPO/CaClO2 体系催化氧化甲苷 合成葡萄糖醛酸及其内酯 学科专业: 化学工艺 研究方向: 有机催化 研 究 生: 马 彦 指导教师: 袁华教授 二?一二年五月 独 创 性 声 明 本人声明所呈交的学位论文是我个人在导师指导下进行的研究工作及取得的研究成果。尽我所知，除文中已经标明引用的内容外，本论文不包含任何其他个人或集体已经发表或撰写过的研究成果。对本文的研究做出贡献的个人和集体，均已在文中以明确方式标明。本人完全意识到本声明的法律结果由本人承担。 学位论文作者签名: 年 月 日 学位论文版权使用授权书 本学位论文作者完全了解我校有关保留、使用学位论文的规定，即:我校有权保留并向国家有关部门或机构送交论文的复印件和电子版，允许论文被查阅。本人授权武汉工程大学研究生处可以将本学位论文的全部或部分内容编入有关数据库进行检索，可以采用影印、缩印或扫描等复制手段保存和汇编本学位论文。 保 密Ο ， 在 年解密后适用本授权书。 本论文属于 不保密Ο。 ) (请在以上方框内打“?” 学位论文作者签名: 指 日 年 月 A Thesis Submitted in Fulfillment of the Requirements 导教师签名: 年 月 for the Degree of Master of EngineeringSynthesis of Glucuronic Acid and Glucurolactone from Methyl Glucoside by Catalytic Oxidation over TEMPO/Ca ClO 2 System Major: Chemical Technology Candidate : My Yan Supervisor: Prof. Yuan Hua Wuhan Institute of Technology Wuhan Hubei P. R. China May 20122 摘 要 摘 要 葡萄糖醛酸内酯D--Glucofuranurono-63-lactone简称葡醛内酯，是一种肝脏解毒剂和免疫功能调节剂;也可作为功能性饮料、食品、减肥药和化妆品等的主要添加剂，在水溶液中能与葡萄糖醛酸相互转化达到平衡。现行工业上以淀粉为原料的硝酸氧化法生产葡醛内酯的工艺已经不能满足市场需要和绿色化学发展要求，该工艺原料淀粉利用率极低，反应选择性差、产品分离提纯困难，收率低，而且能耗较高、环境污染大，因此本论文旨在从原料和氧化体系两方面着手来探索新的合成路线。 本工作选用葡甲苷为原料、TEMPO/CaClO2 为氧化体系来合成葡萄糖醛酸及其内酯。工艺过程是:TEMPO 与 CaClO2 共同作用产生对伯羟基具有催化活性的亚硝鎓离子TEMPO，TEMPO对葡甲苷的伯羟基进行选择性催化氧化得到甲苷酸盐，甲苷酸盐用硫酸酸解后得到葡甲苷酸和副产物硫酸钙，过滤分离，滤液经水解得到葡萄糖醛酸、浓缩、酯化及结晶后制得葡醛内酯。水解产物葡萄糖醛酸采用紫外-可见分光光度法和高效液相色谱进行测定，终产物葡醛内酯分别用熔点测试仪、红外光谱以及高效液相色谱进行分析检测。 实验过程中为给后续催化氧化工艺条件的选择提供依据，首先对TEMPO/CaClO2 体系氧化葡甲苷伯羟基的选择性及其反应机理进行了初步的推理，并讨论了溶剂对选择性氧化反应的影响，推导并简化了动力学方程。动力学实验也表明氧化速率与葡甲苷浓度及次氯酸钙浓度无关，与 TEMPO 浓度呈线性上升关系，而氧化反应的 pH 值是影响氧化速率的主要因素，也决定了 TEMPO 氧化体系能否对葡甲苷的伯羟基进行选择性氧化。适宜的氧化反应条件为:弱碱性pH 值 10 左右，次氯酸钙足量 ， (过量 10左右) 即 CaClO2/MGP 摩尔比为 1.1:1，TEMPO加入催化量即可，以水作溶剂。 在间歇合成工艺的研究中，分为催化氧化工艺和水解工艺。催化氧化反应工艺中，讨论了催化氧化体系反应 pH 值、氧化时间、催化剂用 I 武汉工程大学硕士学位论文 氧化剂用量及 CaClO2 浓度对反应的影响及 TEMPO 回收利用方法。量、在水解反应工艺中讨论了反应中 H2SO4 的作用及反应温度、反应时间和水解 pH 值对产物收率的影响。正交实验结果表明 在催化氧化工艺中各因素对产物收率的影响由大到小的顺序为:pH 值,TEMPO 浓度,CaClO2 浓度,反应时间，其中 pH 值对反应收率的影响最为显著。优化的 工艺条件为:催化氧化反应的 pH 值为 10，反应时间 2 h，TEMPO浓度 MGP/H2Og/ml 为 1:30，CaClO2/MGP 摩尔比为 1:1;水解反应温度 85?，反应 时间 120min，水解 pH 为 1，在此条件下葡萄糖醛酸及其内酯的总收率可达到 92。 同时 HPLC 谱图显示，水解产物中除葡萄糖醛酸、葡醛内酯以及未被氧化的原料 葡甲苷经水解后产生的葡萄糖峰外，基本上没有产生其他杂质峰。以上表明 TEMPO/ CaClO2 体系对甲苷伯羟基的催化氧化具有较好的催化活性和反应选择 性。 TEMPO/ CaClO2 体系催化氧化葡甲苷合成葡萄糖醛酸及其内酯工艺具反应条 件温和、选择性高、易于控制、能耗小、环境友好等优点，具有良好的工业应用前 景。 关键词:葡萄糖醛酸 葡醛内酯 TEMPO/ CaClO2 体系 氧化机理及动力学 催 化氧化 II Abstract Abstract D--Glucofuranurono-63-lactone is abbreviated as glucurolactone.Glucurolactone is usually used as liver antidote conditioning agent withimmune function and also used widely as the main additive in fields such asdrinks foods diet pills cosmetic and so on. Glucuronic acid in aqueoussolution can change into glucurolactone and keep equilibrium state betweenthem. Glucurolactone is produced mainly by nitric acid oxidative methodusing starch as the precursor. This technology has a series of disadvantagessuch as its poor oxidative selectivity the more by-products the longerproduction time the low yield the high energy consumption and the seriousenvironmental pollution. Therefore this paper aims to explore new syntheticroute from the two aspects of raw material and oxidation system. TEMPO/Ca ClO 2 system could selectively oxidate primary hydroxideof glycoside under alkaline conditions. The specific process was explained asfollowing: the combined action of TEMPO and Ca ClO 2 produce nitrosonium ion TEMPO . TEMPO as active components could oxidateprimary hydroxide of glycoside selectively to get the salt of methyl glucosideacid. The salt by acidifation with H2SO4 produce methyl glucoside acid andby-products calcium sulfate. After filtration separation glucuronic acid andits ester were obtained by a series of following-up process to the filtrate:hydrolization concentrate and esterification. In the experimental process themechanism and kinetics of oxidizing glycoside by TEMPO/ Ca ClO 2system was studied briefly. And the glucurolactone was subsequentlyproduced by means of condensation，lactonization，and crystalization. Theintermediate product glucuronic acid could be determined by visiblespectrophotography and high performance liquid chromatography HPLCwhich could evaluate the performance of the catalyst and the final productglucurolactone could be analysed by IR and HPLC. III 武汉工程大学硕士学位论文 For providing evidence to subsequent catalytic oxidation process theselectivity of TEMPO/CaClO2 oxidation primary hydroxide of glycosideand reaction mechanism are studied primarily and the effect of solvent on thereaction is discussed derivation and simplify the dynamic equation thedynamic experiment also shows that oxidation rate is not related to theconcentrate of MGP and CaClO2 but linearly increased as the concentrate ofTEMPO increasing and the major factor that will affect the oxidation rate ispH which is also determine whether the TEMPO oxidation system will makea selective oxidate on primary hydroxide of glycoside. The optimal oxidateconditions are: pH 10 sufficient amount of CaClO2 excessive around 10small amount of TEMPO the molar ratio of CaClO2/MGP is 1.1:1 andwater is used as solvent. The intermittent synthesis process is divided into catalytic oxidationprocess and hydrolysis process. The conditions of catalytic oxidationincluding the influences of the pH reaction time dosage of catalyst dosageof oxidant CaClO2 concentration and the method of recycling of TEMPOwere discussed. The function of H2SO4 in the reaction the influences oftemperature reaction time and the pH on the hydrolysis reaction process werealso discussed in this paper. The results by orthogonal experimental showedthat the value of pH was the most important factor on yield compared withthe TEMPO concentration CaClO2 concentration reaction time. Theoptimal conditions of oxidative process were as follows: the value of pH was10 reaction time was 2h TEMPO concentration MGP/H2Og/ml was 1:30the molar ratio of CaClO2 and glucoside was 1:1 and the optimal conditionsof hydrolysis reaction was as following: temprerature was 85? reaction timewas 120min and pH value was 1. Under these conditions the total yield ofglucuronic acid and its lactone could reach 92. In the meantime no peak ofimpurity was observed from HPLC. It was conclued that the catalytic oxidation of glycoside by TEMPO/ IV AbstractCaClO2 system had better activity and selectivity. This technology adaptedthe demand of green chemistry by its mild reaction conditions easy tocontrol oxidation degree low energy consumption and environment-friendlyso it would have a good prospect for industrial applications. Keywords: Glucuronic acid Glucurolactone TEMPO/CaClO2 systemmechanism and kinetics Catalytic oxidation V武汉工程大学硕士学位论文 VI 目 录 目 录摘 要 ............................................................................................................ IAbstract ........................................................................................................... III目 录 ....................................................................................................... VII引 言 ........................................................................................................... 1第 1 章 文献综 述 ............................................................................................. 3 1.1 甲基-α-D-吡喃葡萄 糖苷的性质及应用 ............................................... 3 1.2 催化剂 TEMPO 及氧化剂次 氯酸钙的性质及用途 ............................ 3 1.2.1 TEMPO 性质及用 途 ................................................................... 3 1.2.2 次氯酸钙的性质及用 途 ............................................................. 4 1.3 葡萄糖醛酸及其内酯的性质与应 用 .................................................... 4 1.3.1 葡萄糖醛酸及其内酯性 质 ......................................................... 4 1.3.2 葡萄糖醛酸及其内酯的用途及市场前 景 ................................. 6 1.4 葡萄糖醛酸及其内酯的制备方 法 ........................................................ 7 1.4.1 生物发酵 法 ................................................................................. 8 1.4.2 多糖水解 法 ................................................................................. 8 1.4.3 化学氧化 法 ................................................................................. 9 1.4.3.1 电化学氧化 法 ................................................................. 9 1.4.3.2 放射化学氧化 法 ............................................................. 9 1.4.3.3 无机氧化 法 ..................................................................... 9 1.4.3.4 催化氧化 法 ................................................................... 11 1.5 葡萄糖醛酸及其内酯的分析检测 方法 .............................................. 15 1.5.1 葡萄糖醛酸内酯的定性鉴 定 ................................................... 15 1.5.2 葡萄糖醛酸内酯的检测--酸碱滴定 法 .................................... 15 1.5.3 葡萄糖醛酸的检测--分光光度 法 ............................................ 16 1.5.4 葡萄糖醛酸的检测--色谱分析法 ............................................ 16 1.6 本工作的主要研究内容和意 义 .......................................................... 18第 2 章 实验条件和过 程 ............................................................................... 20 VII 武汉工程大学硕士学位论文 2.1 主要试剂 .............................................................................................. 20 2.2 仪器设备 .............................................................................................. 21 2.3 实验步骤 .............................................................................................. 22 2.3.1 氧化反应 ................................................................................... 22 2.3.2 水解及内酯化 ........................................................................... 22 2.3.3 结 晶 ........................................................................................... 22 2.4 产物分析与检测 .................................................................................. 23 2.4.1 水解液中葡萄糖醛酸及其内酯的检测 ................................... 23 2.4.1.1 可见分光光度 法 ........................................................... 23 2.4.1.2 HPLC 法测定葡萄糖醛酸和内酯................................. 24 2.4.2 提纯后的葡萄糖醛酸内酯的检 测 ........................................... 29 2.5 催化剂的活性评 价 .............................................................................. 32第 3 章 催化氧化反应机理以及动力学研究 ............................................... 34 3.1 TEMPO 的稳定 性 ................................................................................ 34 3.2 反应体系中亚硝鎓离子的 ........................................... 35 3.3 TEMPO/CaClO2 体系对葡甲苷伯羟产生机理 ....... 基氧化的选择性及其反应机理 的推 理 ................................................................................................... 36 3.3.1 TEMPO 体系氧化葡甲苷伯羟基的选择性 ............................. 36 3.3.2 TEMPO 体系氧化葡甲苷伯羟基反应机理的推理 ................. 36 3.4 反应溶剂对 TEMPO 氧化体系的影响 .............................................. 38 3.5 动力学实 验 .......................................................................................... 38 3.5.1 实验方法 ................................................................................... 38 3.5.2 动力学方程的推导及简化 ....................................................... 39 3.5.3 实验结果与讨 论 ....................................................................... 40 3.5.3.1 动力学实验对氧化机理推理的验证 ........................... 40 3.5.3.2 氧化速率的影响因 素 ................................................... 43 3.5 本章小 结 .............................................................................................. 45第 4 章 间歇反应合成工艺研究 ................................................................... 46 4.1 工艺路线的选定 .................................................................................. 46 VIII 目 录 4.2 催化氧化工艺的研究 .......................................................................... 47 4.2.1 反应 pH 的影响 ........................................................................ 47 4.2.2 氧化时间的影响 ....................................................................... 48 4.2.3 TEMPO 浓度的影响 ................................................................. 49 4.2.4 CaClO2 浓度的影响 ................................................................ 50 4.2.5 正交实验设 计 ........................................................................... 51 4.2.6 TEMPO 的回收利用 ..................................