正己烷/丙酮混合溶剂中非均相催化合成α-生育酚琥珀酸酯

doi:10.16085/j.issn.1000-6613.2018-2423

摘要/Abstract

摘要：

为了实现α-生育酚琥珀酸酯的安全、高效生产，本文以负载化4-二甲氨基吡啶（DMAP）在正己烷/丙酮混合溶剂中催化α-生育酚进行非均相酰化反应。DMAP通过N-烷基化法在硅胶表面进行共价结合负载化，100℃时DMAP的负载量达到最大值0.89mmol/g，TG/DTG表征表明共价键合的DMAP热分解温度为180～330℃，FTIR显示DMAP特征峰出现在1658cm^-1处。低毒性的正己烷/丙酮（4∶1，体积比）混合溶剂能显著提高反应物溶解性及非均相催化反应活性，在此反应体系中优化了反应条件，琥珀酸酐与α-生育酚摩尔比3∶1、反应温度55℃、反应时间21h时，α-生育酚琥珀酸酯产率达最大值91%。反应后过滤回收催化剂，硅胶负载化DMAP循环使用10次后仍保持初始活性的90%以上，滤液经简单地重结晶得到α-生育酚琥珀酸酯纯品，FTIR测试无DMAP特征峰。因此，本文方法对工业化生产α-生育酚琥珀酸酯具有良好应用前景。

关键词: 溶剂, 负载化4-二甲基氨基吡啶, α-生育酚琥珀酸酯, 催化剂, 多相反应

Abstract:

The immobilized 4-dimethylaminopyridine (DMAP) was employed to safely and efficiently catalyze the acylation of α-tocopherol in mixed solvents of hexane and acetone (4∶1). DMAP was covalently bound on the surface of silica gel by N-alkylation reaction and the maximum catalyst loading reached 0.89mmol/g at 100℃. Thermogravimetric analysis / (TG and DTG) indicated that thermal decomposition of DMAP took place at 180—330℃ and Fourier transform infrared spectroscopy (FTIR) analysis showed that the characteristic peak of DMAP appeared at 1658cm^-1. The mixed solvent of hexane and acetone (4∶1) with low toxicities exhibited high solubility to the substrates and hence improved the activity of the heterogeneous catalytic reaction. Next, the influence factors for the acylation of α-tocopherol were systematically investigated. The optimal experimental condition was molar ratio of succinic anhydride to α-tocopherol of 3∶1, the acylation temperature of 55℃ and the reaction time of 21h. Results indicated that the highest yield of α-tocopherol succinate was 91% . After the reaction, the immobilized DMAP was collected by filtration and reused. The results indicated that the activity of the recycled immobilized DMAP was still above 90% after being used for ten runs. After the filtration, α-tocopherol succinate could be easily purified by the recrystallization and the FTIR analysis confirmed the non-existence of DMAP in the product. The excellent results in this work suggest that this technology could become a promising candidate for the industrial production of α-tocopherol succinate.

Key words: solvents, immobilized DMAP, α-tocopherol succinate, catalyst, multiphase reaction

中图分类号:

TQ032

陈丹,张小里,李冰麟,卫龙辉,赵彬侠,张耀中. 正己烷/丙酮混合溶剂中非均相催化合成α-生育酚琥珀酸酯[J]. 化工进展, 2019, 38(9): 4095-4101.

Dan CHEN,Xiaoli ZHANG,Binglin LI,Longhui WEI,Binxia ZHAO,Yaozhong ZHANG. Heterogeneous catalytic synthesis of α-tocopherol succinate in mixed solvents of hexane and acetone[J]. Chemical Industry and Engineering Progress, 2019, 38(9): 4095-4101.

图/表 11

图1 α-生育酚琥珀酸酯的合成图

图2 硅胶负载化DMAP的制备

图3 反应温度对DMAP负载量的影响

图4 氯烷基功能化硅胶、硅胶负载化DMAP和DMAP的热重表征

图5 氯烷基功能化硅胶、硅胶负载化DMAP、DMAP的FTIR表征

表1 单一溶剂对产率的影响

单一溶剂	溶剂极性	产率/%
乙醚	0.01	9.86
正己烷	0.06	51.37
甲苯	2.40	28.49
氯仿	4.40	20.90
丙酮	5.40	13.55
二甲基亚砜	7.20	2.30

图6 混合溶剂对产率的影响

图7 底物摩尔比对产率的影响

图8 反应温度对产率的影响

图9 催化剂的循环利用活性

图10 α-生育酚琥珀酸酯的FTIR谱图

参考文献 21

1	AMIRFAKHRIAN H , ABEDI S M , SADEGHI H , et al . The use of 99mTc-phytate for assessment the protective effect of vitamin E against hepatotoxi-city induced by methotrexat in rat[J]. Nuclear Medicine Review, 2018, 21(1): 8-13.
2	POMPEU M A , CAVALCANTI L F , TORAL F B . Effect of vitamin E supplementation on growth performance, meat quality, and immune response of male broiler chickens: a meta-analysis[J]. Livestock Science, 2018, 208: 5-13.
3	KIM W S , KIM I , KIM W Y , et al . Mitochondria-targeted vitamin E protects skin from UVB-irradiation[J]. Biomolecules Therapeutics, 2016, 24(3): 305-311.
4	DUHEM N , DANHIER U , PREAT V . Vitamin E-based nanomedicines for anti-cancer drug delivery[J]. Journal of Controlled Release, 2014, 182(1): 33-44.
5	YIN Y , NI J , CHEN M , et al . The therapeutic and preventive effect of RRR-alpha-vitamin E succinate on prostate cancer via induction of insulin-like growth factor binding protein-3[J]. Clinical Cancer Research, 2007, 13(7): 2271-2280.
6	TAM K W, HO C T, TU S H , et al . α-Tocopherol succinate enhances pterostilbene anti-tumor activity in human breast cancer cells in vivo and in vitro [J]. Oncotarget, 2018, 9(4): 4593-4606.
7	YIN C H , ZHANG C , GAO M . Enzyme-catalyzed synthesis of vitamin E succinate using a chemically modified Novozym-435[J]. Chinese Journal of Chemical Engineering, 2011, 19(1): 135-139.
8	TAO Y , DONG R , PAVLIDIS L , et al . Using imidazolium-based ionic liquids as dual solvent-catalysts for sustainable synthesis of vitamin esters: inspiration from bio- and organo-catalysis[J]. Green Chemistry, 2015, 18(5): 1240-1248.
9	郑燕升, 莫倩 . α-生育酚琥珀酸酯合成反应工艺及动力学研究[J]. 广东化工, 2008, 35(7): 42-44.
	ZHENG Y S , MO Q . Study on catalytic synthesis and reaction kinetics of α-tocopherol succinate[J]. Guang Dong Chemistry, 2008, 35(7): 42-44.
10	郑燕升, 粟辉 . 三乙胺催化合成维生素E乙酸酯的研究[J]. 精细石油化工, 2006, 17(3): 33-35.
	ZHENG Y S , LI H . Study on the catalytic synthesis of vitamin E succinate by triethyl amine[J]. Speciality Petrochemicals, 2006, 17(3): 33-35.
11	张小里, 董文博, 李彬, 等 . 一种负载化4-(N,N-二甲基)-氨基吡啶催化剂的制备方法: CN106881150A[P]. 2017-06-23.
	ZHANG X L , DONG W B , LI B , et al . Preparation of supported 4-(N,N-dimethyl)-aminopyridine catalyst: CN106881150A[P]. 2017-06-23.
12	TANAKA S , IWATA T , IJI M . Solvent effects on heterogeneous synthesis of cardanol-bonded cellulose thermoplastics[J]. Polymer, 2016, 99(2): 307-314.
13	SAKAKURA A , KAWAJIRI K , OHKUBO T . Widely useful DMAP-catalyzed esterification under auxiliary base and solvent-free conditions[J]. Journal of the American Chemical Society, 2007, 129(47): 14775-14779.
14	CHEN H T , HUH S, WIENCH J W . Dialkylaminopyridine-functionalized mesoporous silica nanosphere as an efficient and highly stable heterogeneous nucleophilic catalyst[J]. Journal of the American Chemical Society, 2005, 127(38): 13305-13311.
15	KHALIL K M S . Cerium modified MCM-41 nanocomposite materials via a nonhydrothermal direct method at room temperature[J]. Journal of Collidand Interface Science, 2007, 315(2): 562-568.
16	KURSUNLU A N , GULER E , DUMRUL H , et al . Chemical modification of silica gel with synthesized new Schiff base derivatives and sorption studies of cobalt and nickel[J]. Applied Surface Science, 2009, 255(21): 8798-8803.
17	YOSHITAKE H , YOKOI T , TATSUMI T . Adsorption of chromate and arsenate by amino-functionalized MCM-41 and SBA-1[J]. Chemistry of Material, 2002, 14(11): 4603-4610.
18	SUNDARAGANESAN G N , KALAICHELVAN S , MEGANATHAN C , et al . FTIR, FT-Raman spectra and ab initio HF and DFT calculations of 4-N,N'-dimethylamino pyridine[J]. Spectrochimica Acta Part A, 2008, 71(3): 898-906.
19	HORCAJADA P , RAMILA A , FEREY G . Influence of superficial organic modification of MCM-41 matrices on drug delivery rate[J]. Solid State Science, 2006, 8(10): 1243-1249.
20	易德莲, 伍林, 王艳, 等 . 生育酚琥珀酸酯合成的研究[J]. 食品科技, 2006 (10): 164-167.
	YI D L , WU L , WANG Y , et al . Study on the synthesis of vitamin E succinate[J]. Food Scence and Technology, 2006 (10): 164-167.
21	曹春英, 赵雪丽, 田大丰 . 维生素E琥珀酸酯的合成及表征[J]. 现代生物医学进展, 2009, 9(2): 315-317.
	CAO C Y , ZHAO X L , TIAN D F . Synthesis and characterization of vitamin E succinate[J]. Progress in Modern Biomedicine, 2009, 9(2): 315-317.

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