CN107954959A - 一种制备2,5-呋喃二甲酸及其前体物质的方法 - Google Patents
一种制备2,5-呋喃二甲酸及其前体物质的方法 Download PDFInfo
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- CN107954959A CN107954959A CN201711171003.1A CN201711171003A CN107954959A CN 107954959 A CN107954959 A CN 107954959A CN 201711171003 A CN201711171003 A CN 201711171003A CN 107954959 A CN107954959 A CN 107954959A
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- acid
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- furandicarboxylic
- furandicarboxylic acid
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Abstract
本发明公开了一种制备2,5‑呋喃二甲酸及其前体物质的方法,采用葡萄糖酸作为原料,首先,通过由葡萄糖酸脱氢酶与NAD(P)H氧化酶组成的双酶耦合***,将葡萄糖酸氧化生成葡萄糖酸衍生物;其次,在醇溶剂中,酸催化条件下,将上步葡萄糖酸衍生物脱水、环化生成2,5‑呋喃二甲酸的前体物质,然后进一步氧化为2,5‑呋喃二甲酸。本发明提供了一种制备2,5‑呋喃二甲酸的新路径,采用来源广泛的葡萄糖酸做为原料,流程简单易于操作,绿色环保,节约了生产成本,具有工业化生产前景。
Description
技术领域
本发明涉及化学酶法制备大宗化学品领域,具体涉及一种制备2,5-呋喃二甲酸及其前体物质的方法。
背景技术
2,5-呋喃二甲酸(furan-2,5-dicarboxylic acid,FDCA),结构式如下:
FDCA是一种极具价值的生物炼制品,具有芳香环以及对称的二酸结构,与对苯二甲酸(p-Phthalic acid, PTA)的结构十分类似。FDCA主要用于合成生物基高分子材料,可有效提高材料的耐热性和机械性能,被认为是石油基单体PTA的理想替代品,同时也能替代间苯二甲酸、己二酸、丁二酸、双酚A 等应用于聚酯、聚酰胺、环氧树脂等生物基聚合物的合成。
目前,FDCA 可由5-羟甲基糠醛(HMF)、糠酸、呋喃、二甘醇酸和己糖二酸等不同起始原料制备。但其主要制备方式仍依赖于以下两个步骤:(1)由六碳糖脱水制备5-羟甲基糠醛(5-hydroxymethylfurfural,HMF);(2)通过氧化HMF来生成FDCA;反应式如下所示:
。
近几十年来,研究者们已深入了解六碳糖制备HMF的脱水机制,并利用离子液体、双相***等方法来改进和优化制备方法(李雪辉等,CN201610820992.1)。HMF氧化制备FDCA也有大量研究,目前主要集中在通过使用不同类型的纳米颗粒作为催化剂和氧化条件来实现(李峰等,CN201710016617.6)。例如,使用几种类型的纳米颗粒如Pt、Pt/Bi、Pd和用Pd或Pt改性的Au,在温和条件下,氧化HMF水溶液制备FDCA(傅杰等,CN201710108023.8)。
然而除了果糖外,其他六碳糖制备HMF过程中产物选择性不高,而HMF自身固有的不稳定性,使得HMF即使大量生成,也会在反应过程中分解为乙酰丙酸,甲酸及胡敏素等副产物;而HMF氧化为FDCA的过程,也要求高度的氧化选择性,氧化不完全产生的5-甲酰基呋喃甲酸、5-羟甲基呋喃甲酸、呋喃二甲醛等中间产物会对后续分离产生极大影响,同时氧化条件严苛,需要大量的碱中和,这些都使得整个反应历程的成本增加,最终产物FDCA的价格无法与对苯二甲酸竞争。
而本发明所涉及的一类葡萄糖酸衍生物,如:5-酮基-D-葡萄糖酸(5-keto-D-gluconic acid, 5-KGA)、2-酮基-D-葡萄糖酸,或者2-酮基-L-古龙酸,或者2-脱氢-3-脱氧葡萄糖酸,或者4-脱氧-5-脱氢葡萄糖二酸等具有与果糖类似的酮基结构,能够自发形成呋喃环结构,从而为脱水制备FDCA提供了新的途径。
而此类葡糖酸衍生物一般由葡萄糖酸特定位置羟基,例如5-KGA 由葡萄糖酸的5-位羟基,氧化而获得。化学氧化法选择性差、副产物多,如德国科学家Kiliani等在1922年提出了硝酸化学法用于氧化葡萄糖酸制备5-KGA,收率仅为10-12%。相较而言,生物法可以特异性的对葡萄糖酸的特定位置羟基进行氧化,从而高选择性的获得葡萄糖酸衍生物。另外,体外多酶催化方法灵活,可操作性强,是优良的葡萄糖酸衍生物获取方法。
体外多酶催化葡萄糖酸到葡萄糖酸衍生物,主要依赖于葡萄糖酸脱氢酶和NAD(P)H氧化酶。在酶促反应中葡萄糖酸脱氢酶是一种辅酶依赖性的还原酶,对NAD(P)+存在极其强烈的依赖性,需要添加辅酶NAD(P)+,葡萄糖酸脱氢酶在NAD(P)+存在下可以催化葡萄糖酸为葡萄糖酸衍生物,并生成NAD(P)H和H+;与此同时,在于体系中加入NAD(P)H氧化酶之后,NAD(P)H氧化酶能够在氧气存在下,将NAD(P)H催化脱氢形成NAD(P)+,实现辅酶原位在生以及葡萄糖酸的完全转化,反应式如下所示:
。
发明内容
针对目前报道的FDCA制备过程中存在的缺陷,本发明的目的在于提供一种由葡萄糖酸通过化学酶法来制备FDCA的方法,避免了中间产物HMF易于分解、HMF氧化不完全所导致FDCA产率低的缺陷。
为了实现上述目的,本发明采用的技术方案为:
一种制备2,5-呋喃二甲酸及其前体物质的方法,它包括以下步骤:
1、以含有葡萄糖酸脱氢酶、NAD(P)H氧化酶的整细胞或葡萄糖酸脱氢酶、NAD(P)H氧化酶的游离酶为催化剂,在弱碱性条件下,NADP+或NAD+作为氢受体,催化葡萄糖酸制备葡萄糖酸衍生物;
2、将步骤1)所得的葡萄糖酸衍生物加入溶剂中,在酸催化条件下反应,并将反应液中和、干燥,柱层析后得到2,5-呋喃二甲酸前体物质;
3、将步骤2)所得的2,5-呋喃二甲酸前体物质通过氧化剂或催化剂催化氧化,最终获得2,5-呋喃二甲酸。
本发明步骤1)所述的葡萄糖酸脱氢酶由含有葡萄糖酸脱氢酶基因的重组菌所表达,所述的葡萄糖酸脱氢酶基因来源于氧化葡萄糖酸杆菌 (Gluconobacter oxydans),或弱氧化葡糖杆菌 (Gluconobacter suboxydans),或巴氏醋杆菌 (Acetobacterpasteurianus),或攀膜醋杆菌 (Acetobacter ascendens),或猪链球菌 (Streptococcussuis),或克雷伯氏菌 (Klebsiella sp),或产黄青霉 (Penicillium chrysogenum)等其他含有葡萄糖酸脱氢酶的菌种。所述的葡萄糖酸脱氢酶由含有该基因的重组菌E.coli BL21(DE3)所表达,表达载体选用但不限于pet-28a(+)。
本发明步骤 1)所述的NAD(P)H氧化酶由含有NAD(P)H氧化酶基因的重组菌所表达,所述的NAD(P)H氧化酶基因来源于旧金山乳杆菌 (Lactobacillussanfranciscensis),或乳酸乳球菌 (Lactococcus lactis),或褐家鼠 (Rattusnorvegicus),或哈茨木霉(Trichoderma harzianum)等其他含有NAD(P)H氧化酶的物种。所述的NAD(P)H氧化酶由含有该基因的重组菌E. coli BL21(DE3)所表达,表达载体选用但不限于pet-28a(+)。
本发明步骤1)中催化反应体系是:1.5-150 g/L葡萄糖酸钠、50-5000 U的葡萄糖酸脱氢酶、70-8000 U的NAD(P)H氧化酶和0.05-0.2 mmol/L的NADP+或NAD+,在pH7.5-9.0、反应温度25-45 ℃、搅拌转速180-280 rpm以及通气量1-3 VVM条件下反应1-24 h,得到葡萄糖酸衍生物转化液。
本发明步骤1)中所述的葡萄糖酸衍生物为醛酸,或者5-酮基-D-葡萄糖酸,或者2-酮基-D-葡萄糖酸,或者2-酮基-L-古龙酸,或者2-脱氢-3-脱氧葡萄糖酸,或者4-脱氧-5-脱氢葡萄糖二酸等酮酸类物质。
本发明步骤2)所述醇溶剂为甲醇、乙醇、丙醇、异丙醇、丁醇、仲丁醇、异丁醇、1,3-丙二醇、1,2-丙二醇等C1-C10的一元至多元醇的一种或者几种。
本发明步骤2)所述催化使用的催化剂为盐酸、硫酸、硝酸等无机酸,或者SO4 2﹣/ZrO2、SO4 2﹣/TiO2、SO4 2﹣/Fe2O3等固体酸,或者离子液体等催化剂,催化剂用量为0.3-3 M。
本发明步骤2)中采用反应温度为20-200℃;反应时间为1-72 h。
本发明步骤2)中所述2,5-呋喃二甲酸前体物质为2-甲酰基-5-呋喃羧酸酯类,或者2-半缩醛-5-呋喃羧酸酯类,2-缩醛-5-呋喃羧酸酯类等此类物质。
本发明步骤3)中所采用氧化剂为高锰酸钾、双氧水等化学氧化剂,或者氧气等其他常见氧化剂等。
本发明步骤3)中所采用催化剂为Co2+/Mn2+/Br-等均相催化剂,或以金(Au)、钯(Bd)、钌(Ru)、铂(Pt)等为核心的贵金属催化剂等。
本发明采用葡萄糖酸作为原料,首先,通过由葡萄糖酸脱氢酶与NAD(P)H氧化酶组成的双酶耦合***,将葡萄糖酸氧化生成葡萄糖酸衍生物;其次,在醇溶剂中,酸催化条件下,将上步葡萄糖酸衍生物脱水、环化生成2,5-呋喃二甲酸的前体物质,然后进一步氧化为2,5-呋喃二甲酸。本发明提供了一种制备2,5-呋喃二甲酸的新路径,采用来源广泛的葡萄糖酸做为原料,流程简单易于操作,绿色环保,节约了生产成本,具有工业化生产前景。
有益效果:与现有技术相比,本发明具有如下优点:
1、本发明所述的技术方案采用酶法催化生成葡萄糖酸衍生物,选择性高,反应温度低,效率高,能耗低。
2、本发明联合应用NAD(P)H氧化酶,不仅可以实现NADP+再生,且副产物为水,对主产物分离纯化无影响,同时可以促进主反应的平衡向产物葡萄糖酸衍生物方向移动,转化率可达99%以上。
3、本发明所述的技术方案无需生成5-羟甲基糠醛,避免5-羟甲基糠醛本身所具有的不稳定的特性所造成的目的产物产率低下,氧化过程副产物多等问题。
4、本发明所述的技术方案过程简单,酶催化过程中辅酶可循环使用,反应更为绿色环保。
附图说明
图1、葡萄糖酸脱氢酶SDS-PAGE电泳图;
图2、NAD(P)H氧化酶SDS-PAGE电泳图;
图3、实施例7产物核磁共振氢谱;
图4、实施例7产物核磁共振碳谱;
图5、实施例8产物核磁共振氢谱;
图6、实施例8产物核磁共振碳谱。
具体实施方式
根据下述实施例,可以更好地理解本发明。然而,实施例所描述的内容仅用于说明本发明,而不应当也不会限制权利要求书中所详细描述的本发明。
实施例1:来源于Gluconobacter oxydans的葡萄糖酸脱氢酶基因(gdh)的克隆
Gluconobacter oxydans购于中国普通微生物菌种保藏管理中心(CGMCC)。氧化葡萄糖酸杆菌培养采用培养基配方(g/L)为:葡萄糖100,酵母提取物10,碳酸钙20,琼脂15,完全溶解于去离子水中,调节pH至6.8,定容,高压蒸汽灭菌。
将氧化葡萄糖酸杆菌接种于LB液体培养基中,37℃培养至对数生长期,使用DNAKit(TIANGEN,China)提取嗜热链球菌基因组。构建表达载体所用的引物加设酶切位点,引物序列如下:
上游引物(葡萄糖酸脱氢酶-sense含EcoR I)为:
5’-CCGGAATTCATGAGTACCTCTCTTTTTG-3’
下游引物(葡萄糖酸脱氢酶-anti含Hind III)为:
3'-CCCAAGCTTTCAAAGAGAGACCGTAATC- 5'
所有引物均由苏州金唯智生物科技有限公司合成。基因的PCR条件为94℃变性5min,按如下参数循环30次:95℃变性15s,60℃退火15s,72℃延伸30s。最后72℃延伸6min。反应所得到的产物分别用0.8%的琼脂糖凝胶电泳分析结果。经凝胶成像***成像确认片段大小正确后,采用TaKaRa公司的DNA纯化回收试剂盒(TaKaRa Agarose Gel DNA Purification)回收目的片段用于重组表达载体pET-28a-gdh的构建。
实施例2:重组表达载体pET-28a-gdh的构建
用EcoR I及Hind III分别酶切(购于Novagen默克中国)及所扩增含有两个酶切位点的目的基因,分别胶回收已双酶切的目的片段和表达载体,将已双酶切的表达载体pET-28a与目的基因(Genbank中的收录号为NC_019396.1)用T4-DNA连接酶(购于TaKaRa公司)进行过夜连接,得到重组载体pET-28a-gdh;将10μL的连接产物加入的大肠杆菌BL21感受态细胞中,冰上放置30min,42℃热激90s。冰上放置2min。加入预热的0.45mL LB培养基。220rpm,37℃,1h。将200μL菌液加入含有30μg/mL的卡那霉素的平板上,37℃过夜培养12-16h,得到重组菌E.coli BL21(含pET-28a-gdh)。
实施例3:来源于Lactobacillus sanfranciscensis的NAD(P)H氧化酶基因(nox)的来源及获得
本实施例提供了编码具有NAD(P)H氧化酶活性的多聚核苷酸分子,该核苷酸分子编码的氨基酸序列在UniProt中收录号为Q9F1X5,并由苏州金唯智生物科技有限公司人工合成。
实施例4:重组表达载体:pET-28a-nox的构建
用EcoR I及Nco I分别酶切(购于Novagen默克中国)及含有两个酶切位点的目的基因(实施例3中人工合成获得),分别胶回收已双酶切的目的片段和表达载体,将已双酶切的表达载体pET-28a与目的基因,将10 μL的连接产物加入的大肠杆菌BL21感受态细胞中,冰上放置30 min,42 ℃热激90 s。冰上放置2 min。加入预热的0.45 mL LB培养基。220 rpm,37℃,1 h。将200 μL菌液加入含有30 μg/mL的卡那霉素的平板上,37℃过夜培养12-16 h,得到重组菌E.coli BL21(含pET-28a-nox)。
实施例5:重组菌的发酵及冻干细胞的制备
在发酵罐中培养重组菌(实施例2及实施例4中构建的重组菌)。发酵的种子培养基采用LB培养基。发酵培养基为TB培养基: 酵母提取物25 g/L,蛋白胨15 g/L,NaCl 10 g/L,葡萄糖2 g/L,乳糖3 g/L。发酵培养基灭菌前pH调节至7.2,于110℃灭菌20min。发酵开始时,按1.5%接种量接种OD600约为1.0的新鲜种子液至发酵罐中。控制发酵液的温度在30℃和维持溶氧在10-30%。发酵结束后8000rpm离心10min收集菌体,称量湿细胞重量。将湿细胞用0.85%生理盐水洗涤次后放置-80℃冰箱中冷冻,再置于冻干机中进行冷冻干燥即可制得冻干细胞。
将冻干细胞用缓冲液充分悬浮,超声破碎后,10000rpm/min,4℃离心10min,取上清。葡萄糖酸脱氢酶酶活的测定:酶反应体系包括100mM Tris-HCl缓冲(pH 8.0),10mM 葡萄糖酸钠,1mM NADP+,30℃,340nm处测定吸光值的上升。酶活定义为每分钟内生成1μmolNADPH所需要的酶量为一个酶活单位U。蛋白采用Brandford法进行测定。结果显示,对照菌E.coli BL21(含pET-28a)的比酶活为0,而重组菌E.coli BL21(含pET-28a-gdh)的比酶活为20U/mg。
NAD(P)H氧化酶酶活的测定:酶反应体系包括100mM Tris-HCl缓冲(pH 8.0),0.2mM NADPH,30℃,340nm处测定吸光值的下降。酶活定义为每分钟内消耗1umol NAD(P)H所需要的酶量为一个酶活单位U。蛋白采用Brandford法进行测定。结果显示,对照菌E.coliBL21(含pET-28a)的比酶活为0.2 U/mg,而重组菌E.coli BL21(含pET-28a-nox)的比酶活为15U/mg。
实施例6:葡萄糖酸衍生物之一-5-酮基-D-葡萄糖酸的制备
取实施例5中冻干细胞各10g,悬浮于的200mL的pH 8.0 Tris-HCl缓冲中。使用高压均质机(-20℃、8.0×107 Pa)对细胞进行破碎。细胞破碎液经4℃、10000rpm/min离心30min后,弃沉淀,上清即为含有葡萄糖酸脱氢酶及NAD(P)H氧化酶的粗酶液。加入葡萄糖酸钠150g/L,NAD(P)+0.1mmol/L,在反应温度30℃,搅拌转速280rpm以及通气量3VVM的条件下反应24h,并在反应过程中按需求进行取样。样品在95℃中加热5min,10000rpm/min离心5min取上清进行HPLC检测葡萄糖酸钠及5-酮基-D-葡萄糖酸的含量。在双酶耦合的反应体系中,5-酮基-D-葡萄糖酸浓度随时间不断增加,葡萄糖酸钠转化率大于99%。
产物的检测方法:
采用高效液相色谱(HPLC)测定葡萄糖酸钠及5-酮基-D-葡萄糖酸。高效液相色谱仪采用日本岛津公司,色谱柱为美国Bio-Rad公司Aminex HPX-87H column(300×7.8mm)色谱柱,流动相为5mM H2SO4,流速0.6mL/min,柱温为35℃;采用示差检测器。
实施例7:葡萄糖酸衍生物之一-5-酮基-D-葡萄糖酸的脱水
取5-酮基-D-葡萄糖酸200mg于5ml的甲醇中,并加入50mg固体酸Amberlst75,65℃油浴反应24h,HPLC检测显示5-酮基-D-葡萄糖酸转化率为100%;以展开剂比例为3:1(石油醚:乙酸乙酯)展开,并分离纯化后,GC检测显示FDCA前体物质2-二甲氧基甲基-5-呋喃羧酸 甲酯收率为75%。1H NMR(400MHz,CDCl3)δH:7.13(1H,s,C3-H),6.52(1H,s,C4-H),5.43 (1H,s,C6-H),3.86(3H,s,C7-H),3.34(6H,s,C8-H,C9-H)。13C NMR(101MHz,CDCl3)δ c:159.10,155.13,144.38,118.49,110.49,97.61,53.15,52.02。
实施例8:葡萄糖酸衍生物之一-5-酮基-D-葡萄糖酸的脱水
取5-酮基-D-葡萄糖酸200mg于5ml 0.3M的丁醇硫酸中,110℃油浴反应4h,HPLC检测显示5-酮基-D-葡萄糖酸转化率为100%;以展开剂比例为6:1(石油醚:乙酸乙酯)展开,并分离纯化后,GC检测显示FDCA前体物质2-甲酰基-5-呋喃羧酸丁酯收率为65%。1H NMR(500MHz,CDCl3)δH:9.88(1H,s,C6-H),7.34(2H,m,C4-H,C3-H),4.43(2H,t,C7-H), 1.83(2H,m,C8-H),1.53(2H,m,C9-H),1.05(3H,m,C10-H)。13C NMR(126MHz,CDCl3)δc: 179.34,158.45,154.23,148.36,119.16,118.78,66.04,30.95,19.42,13.97。
产物的检测方法:
采用高效液相色谱(HPLC)测定5-酮基-D-葡萄糖酸。高效液相色谱仪采用日本岛津(Shimadzu)公司LC-20A,色谱柱为美国Bio-Rad公司Aminex HPX-87H column(300×7.8mm)色谱柱,流动相为5mM H2SO4,流速0.6mL/min,柱温为35℃;采用示差检测器。
采用气相色谱(GC)测定FDCA前体物质。气相色谱仪采用日本岛津(Shimadzu)公司GC-2010,色谱柱Rtx-5MS,气化室温度240℃,色谱柱初温40℃,保留5min,升温速率为7.5℃/min,终温240℃,保留时间15min,检测器(FID)温度240℃。载气:氦气,流速:0.43mL/min。
实施例9:FDCA---2-甲酰基-5-呋喃羧酸丁酯催化氧化制备FDCA
向高压反应釜中加入100 ml ,0.25 M K2CO3的水溶液,并加入1.5 g高锰酸钾,1.82 g2-甲酰基-5-呋喃羧酸丁酯,充入1 MPa 氧气为氧源,磁力搅拌下,90 ℃反应6 h。经检测底物转化率为96.3 %,FDCA收率为89 %。
以上所述仅为本发明的优选实施方案,应当指出,对于本技术领域的普通技术人员来说,在不脱离本发明原理的前提下,还可作出若干改进和润饰,这些改进和润饰也应视为本发明的保护范围。
Claims (10)
1.一种制备2,5-呋喃二甲酸及其前体物质的方法,其特征在于,它包括以下步骤:
1)以含有葡萄糖酸脱氢酶、NAD(P)H氧化酶的整细胞或葡萄糖酸脱氢酶、NAD(P)H氧化酶的游离酶为催化剂,在弱碱性条件下,NADP+或NAD+作为氢受体,催化葡萄糖酸制备葡萄糖酸衍生物;
2)将步骤1)所得的葡萄糖酸衍生物加入溶剂中,在酸催化条件下反应,并将反应液中和、干燥,柱层析后得到2,5-呋喃二甲酸前体物质;
3)将步骤2)所得的2,5-呋喃二甲酸前体物质通过氧化剂或催化剂催化氧化,最终获得2,5-呋喃二甲酸。
2.根据权利要求1所述的一种制备2,5-呋喃二甲酸及其前体物质的方法,其特征在于,步骤1)所述的葡萄糖酸脱氢酶由含有葡萄糖酸脱氢酶基因的重组菌所表达,所述的葡萄糖酸脱氢酶基因来源于氧化葡萄糖酸杆菌 (Gluconobacter oxydans),或弱氧化葡糖杆菌(Gluconobacter suboxydans),或巴氏醋杆菌(Acetobacter pasteurianus),或攀膜醋杆菌 (Acetobacter ascendens),或猪链球菌(Streptococcus suis),或克雷伯氏菌 (Klebsiella sp),或产黄青霉(Penicillium chrysogenum)等其他含有葡萄糖酸脱氢酶的菌种。
3.根据权利要求1所述的一种制备2,5-呋喃二甲酸及其前体物质的方法,其特征在于,步骤 1)所述的NAD(P)H氧化酶由含有NAD(P)H氧化酶基因的重组菌所表达,所述的NAD(P)H氧化酶基因来源于旧金山乳杆菌 (Lactobacillus sanfranciscensis),或乳酸乳球菌 (Lactococcus lactis),或褐家鼠(Rattus norvegicus),或哈茨木霉(Trichoderma harzianum)等其他含有NAD(P)H氧化酶的物种。
4.根据权利要求1所述的一种制备2,5-呋喃二甲酸及其前体物质的方法,其特征在于,步骤1)中催化反应体系是:1.5-150 g/L葡萄糖酸钠、50-5000 U的葡萄糖酸脱氢酶、70-8000 U的NAD(P)H氧化酶和0.05-0.2mmol/L的NADP+或NAD+,在pH7.5-9.0、反应温度25-45℃、搅拌转速180-280 rpm以及通气量1-3 VVM条件下反应1-24 h,得到葡萄糖酸衍生物转化液。
5.根据权利要求1所述的一种制备2,5-呋喃二甲酸及其前体物质的方法,其特征在于,步骤1)中所述的葡萄糖酸衍生物为醛酸,或者5-酮基-D-葡萄糖酸,或者2-酮基-D-葡萄糖酸,或者2-酮基-L-古龙酸,或者2-脱氢-3-脱氧葡萄糖酸,或者4-脱氧-5-脱氢葡萄糖二酸等酮酸类物质。
6.根据权利要求1所述的一种制备2,5-呋喃二甲酸及其前体物质的方法,其特征在于,步骤2)所述溶剂为C1-C10的一元至多元醇中的一种或者几种。
7.根据权利要求1所述的一种制备2,5-呋喃二甲酸及其前体物质的方法,其特征在于,步骤2)所述催化使用的催化剂为无机酸、固体酸或者离子液体催化剂,所述无机酸包括但不限于盐酸、硫酸、硝酸;所述固体酸包括但不限于SO4 2﹣/ZrO2、SO4 2﹣/TiO2、SO4 2﹣/Fe2O3,催化剂用量为0.3-3 M。
8.根据权利要求1所述的一种制备2,5-呋喃二甲酸及其前体物质的方法,其特征在于,步骤2)中反应温度为20-200℃;反应时间为1-72 h。
9.根据权利要求1所述的一种制备2,5-呋喃二甲酸及其前体物质的方法,其特征在于,步骤2)中所述2,5-呋喃二甲酸前体物质为2-甲酰基-5-呋喃羧酸酯类,或者2-半缩醛-5-呋喃羧酸酯类,2-缩醛-5-呋喃羧酸酯类等此类物质。
10.根据权利要求1所述的一种制备2,5-呋喃二甲酸及其前体物质的方法,其特征在于,步骤3)中所采用氧化剂为高锰酸钾、双氧水等化学氧化剂,或者氧气等其他氧化剂等,步骤3)中所采用催化剂为Co2+/Mn2+/Br-等均相催化剂,或以金、钯、钌、铂等为核心的贵金属催化剂等。
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