一锅法制备1-吡啶基-3-哌啶-4-甲酸的合成研究

N杂环类分子是一类重要的医药切块分子,多用作多肽类医药分子的合成原料中间体。报道了一种N杂环类分子1-吡啶基-3-哌啶-4-甲酸新的合成方法。高压反应釜依次加入3-溴吡啶、4-哌啶甲酸乙酯、碳酸钾、N-甲基吡咯烷酮,反应釜密封好,升温至180℃,压力保持0.5MPa,液质监测反应,反应72h,原料反应完毕。将反应体系冷却至室温后抽滤,滤饼用甲醇打浆后再次抽滤,将滤液浓缩后再甲醇重结晶得黄色粉末,产率最高可达46%。该合成方法,碱性高压条件,一锅法得到目标化合物,极大地降低了工业成本,且后处理方法简单且收率高,具有工业化生产前景。

Synthesis and Antitumor Activity of 3-[2-(4-Hydroxy-Phenyl)-Ethyl]-Benzo[d] Isoxazole-4,6-Diol

A new phloretin derivative 1 3-[2-(4-hydroxy-phenyl)-ethyl]-benzo[d] isoxazole-4,6-diol (yield 63%) was synthesized from phloretin by carbonyl nucleophilic addition condensation reaction. Its structure was characterized by 1H NMR, 13C NMR and HR-MS. The phloretin, compound 1, resveratrol and acetylated resveratrol were determined by comparing them with paclitaxel. Anti-tumor activity of alcohol on SPC-A1, EC109, A549, MCF-7 and MDA-MB-231 cell lines. Compound 1 showed better antitumor activity than docetaxel against A549 tumor cells.

Al_(2)(SO_(4))_(3)催化热解油转化生产酯类燃料

酸类、糖类等不稳定组分的存在是制约热解油直接用作生物燃料的主要因素。为了解决此问题,提出采用Al_(2)(SO_(4))_(3)催化剂将这些不稳定成分酯化为燃料类化合物的途径。首先,分别以单模型化合物左旋葡萄糖或乙酸为原料,考察各种金属硫酸盐催化其转化制备乙酰丙酸乙酯或乙酸乙酯的能力,筛选出催化性能最好的催化剂;其次,以左旋葡萄糖和乙酸的模型混合物为原料,探究Al_(2)(SO_(4))_(3)催化同时转化制备酯类的最佳反应条件;最后,以真实热解油为原料,验证Al_(2)(SO_(4))_(3)在最佳反应条件下催化酯化的可行性。结果表明,酯化后热解油中大部分酸、糖、醛消失,同时产生大量的酯和缩醛,酯类和缩醛类占改性热解油总色谱面积的39.5%。Al_(2)(SO_(4))_(3)能有效将热解油中的酸类、糖类等不稳定组分酯化为燃料类化合物,可为热解油转化制备生物燃料提供借鉴。

氟代溶剂2,2-二氟乙基乙酸酯和2,2,2-三氟乙基乙酸酯用于4.85 V LiNi_(0.5)Mn_(1.5)O_(4)|石墨电池

高性能的锂离子电池推进了电动汽车的发展,但传统材料限制了电池能量密度的进一步提升。LiNi_(0.5)Mn_(1.5)O_(4)(LNMO)作为正极材料可显著提高电池的能量密度,并降低成本,但高达4.7 V的电压平台难以匹配当前的电解液体系。因此,开发一种耐高电压的电解液体系是LNMO材料应用的关键。为了改善这个问题,本文分别以耐高电压的2,2-二氟乙基乙酸酯(DFEA)和2,2,2-三氟乙酸乙酯(TFEA)作为替代溶剂,部分替代传统电解液中常用的氟代碳酸甲乙酯(FEMC)溶剂,从而提升了LNMO/石墨锂离子电池的性能。实验结果表明,使用DFEA和TFEA替代FEMC后,电解液的电导率上升,粘度下降。与未替代溶剂电池相比,使用DFEA和TFEA替代电解液的电池在常温下循环的容量保持率分别由45.97%提升到75.45%和68.36%,表明这种溶剂替代策略具有可行性。

4-氯乙酰乙酸乙酯的连续合成工艺

文章采用微通道反应器进行连续氯化反应来提高4-氯乙酰乙酸乙酯的收率。将双乙烯酮和氯气分别溶解于二氯甲烷,再通过计量泵按比例泵入微通道反应器中,在正压条件下以一定反应温度、时间进行反应。其结果表明,在双乙烯酮含量为20%、氯气含量为10%、氯气与双乙烯酮摩尔比为1.05∶1.00、反应温度为-10℃、流速为60 mL/min、停留时间为1 min的反应条件下制备的4-氯乙酰乙酸乙酯产品,其产品收率达到96.7%,产品提纯后含量达到98%以上。

浓香型白酒发酵过程中4-甲/乙基愈创木酚的代谢规律分析

4-甲/乙基愈创木酚是浓香型白酒中重要的风味和健康成分,是影响白酒烟熏、丁香风味及抗氧化、抗炎等健康特性的重要因素,但其在浓香型白酒发酵过程中的代谢规律不清晰。因此,该文首先采用真空辅助吸附萃取分析法(vacuum assisted adsorption extraction,VASE)结合GC-MS分析揭示浓香型白酒发酵过程中4-甲/乙基愈创木酚及其前体物质的变化规律。研究发现:(1)4-甲/乙基愈创木酚的前体物质(阿魏酸、4-乙烯基愈创木酚)是由原料提供的,其中对阿魏酸的贡献粮食约为65.13%、大曲20.69%、稻壳14.18%;对于4-乙烯基愈创木酚的贡献稻壳最大,约为98.29%、大曲0.28%、粮食1.33%;(2)发酵过程中,4-甲/乙基愈创木酚主要在窖池发酵阶段产生,尤其是于窖池发酵后期产生,4-甲基愈创木酚由53.63μg/kg增长到93.78μg/kg,生成率达74.86%,4-乙基愈创木酚的含量由13.14μg/kg达到53.98μg/kg,生成率超过300%。该研究系统揭示了浓香型白酒发酵过程中4-甲/乙基愈创木酚及其前体物质的变化规律,为调控4-甲/乙基愈创木酚代谢提高浓香型白酒风味健康品质具有重要意义。

Synthesis and Crystal Structure of Tri(4-(3-hydroxy2-ethyl-4-pyridinone-1-yl)-aniline Condensation Salicylaldehydato) Monohydratotricopper(II)Dimethylformamide Monohydrate Solvate

The title complex [Cu3L3(H2O)]DMFH2O (H2L = 4-(3-hydroxy-2-ethyl-4- pyridinone-1-yl)-aniline condensation salicylaldehyde) was obtained. The single-crystal X-ray study shows that it is a trinuclear compound [Cu3(C20H15N2O3)3(H2O)]DMFH2O. The coordi- nation sphere about each copper ion in the complex consists of two oxygen atoms from hydroxylpyridinone moiety of one ligand and one oxygen and one nitrogen atoms from salicyladehyde Schiff-base moiety of another ligand arranged in a slightly distorted square planar geometry. Among the three copper ions, one (Cu(2)) is coordinated by the other oxygen atom of water molecule on the fifth coordinate position to form a distorted square pyramid geometry. The crystal is of monoclinic, space group P21/c with a = 12.9202(5), b = 27.197(1), c = 17.0116(7) ? b = 100.588(1), V = 5875.9(4) 3, Z = 4, C63H57N7O12Cu3, Mr = 1294.78, Dc = 1.464 g/cm3, m = 1.146 mm-1, F(000) = 2668, R = 0.0784 and wR = 0.1546 for 6926 observed reflections with I > 2s(I). The differences of coordinate bond lengths are observed between anhydrous and hydrous units: in the former unit, the average bond lengths are 1.978 ?for CuN (azomethine), 1.883 ?for CuO (phenolic) in Schiff-base moiety, 1.959 ?for CuO (keto), and 1.919 ?for CuO (hydroxy) in hydroxypyridinone moiety; while those in the latter are longer with the following corresponding values: 1.985(5), 1.908(5), 1.993(5) and 1.919(4) ? respectively. The Cu(2)O (water) bond length is 2.375(6) ?

产4-乙基愈创木酚菌株的筛选、鉴定及其在酱油酿造中的应用

该研究采用传统培养分离方法结合耐盐性及4-乙基愈创木酚(4-EG)生产能力测定,从广式高盐稀态酱油发酵酱醪中分离筛选能转化阿魏酸(FA)生成4-EG的细菌,通过形态观察及分子生物学技术对分离菌株进行鉴定,同时对其生长特性进行研究,并将其应用于酱油酿造。结果表明,分离筛选得到一株高产4-EG的菌株JLB30-2,被鉴定为枯草芽孢杆菌(Bacillus subtilis),该菌株在45℃、160 r/min、20%盐含量环境下,能将发酵液中的FA转化为4-EG。菌株JLB30-2在盐含量为20%的酱醪中培养60 d,4-EG含量最高达29.75 mg/L,是对照组(6.85 mg/L)的3.34倍,同时增加了酱油中氨基酸、酮类化合物的含量,强化了酱油醇香和酱香,提高了酱油的感官品质,对改善提升酱油品质具有重要实用价值。

Synthesis and Crystal Structure of cis-Bis(3-hydroxy2-ethyl-4-pyranonato)dioxomolybdenum(Ⅵ)

The complex MoO2(C7H7O3)2 has been prepared by the reaction of 3-hydroxy- 2-ethyl-4-pyranone with (NH4)6Mo7O244H2O. The single-crystal X-ray study shows that the coordination sphere about the molybdenum atom in the complex consists of six oxygen atoms arranged in a distorted octahedral geometry with the dioxo ligands in cis positions. The crystal is of monoclinic, space group P21/c with a = 8.3968(2), b = 12.7534(4), c = 14.5443(4) ? b = 96.277(1), V = 1548.18(7) ?, Z = 4, C14H14O8Mo, Mr = 406.19, Dc = 1.743g/cm3, m = 0.886mm-1, F(000) = 816, R = 0.0444 and wR = 0.1091 for 2336 observed reflections with I>2s(I). The average Mo=O bond length is 1.695(4) ? The two ketonic oxygen atoms of the pyranone moieties are trans to the oxo ligands and the hydroxy oxygen atoms are trans to each other. The average MoO bond lengths are 2.248(4) ?for the ketone oxygens and 2.005(3) ?for the hydroxy oxygens. The average ligand bite angle of OMoO is 75.2(2) and the bond angle between two Mo=O is 105.1(2). The dihedral angle is 79.16(2)?between two chelate ring planes.

Synthesis and Crystal Structure of Tris(N-p-methylphenyl-3-hydroxy-2-ethyl-4-pyridinonato)iron(III)

The complex [Fe(C14H14NO2)3]2H2O has been prepared by reaction of N-p-methylphenyl-3-hydroxy-2-ethyl-4-pyridinone with FeCl36H2O. A single-crystal X-ray study shows that the iron atoms lie in a trigonally distorted octahedral environment coordinated to the hydroxy and ketone oxygen atoms of three ligands in the mer configuration Mr=773.57(C42H46N3O8Fe). The crystal is hexagonal with space group P31c; a=15.943(2), c=17.612(4)? V=3877.0(12)?, Z=4, Dc=1.325g/cm3, m=0.445mm-1, F(000)=1634, R=0.0446, wR= 0.1154 for 3085 reflections with I >2s(I). The bond lengths from iron to oxygens are 1.980(1)?for the ketone oxygens and 2.071(1)?for the hydroxy oxygens. The molecule exhibits the expected propeller shape, and the angle of the trigonal twist is 48.37. The dihedral angles are 0.5(2)?between chelate ring plane and pyridine ring plane and 71.31(7)?between pyridine ring plane and benzene ring plane. The solvent H2O(O(3) and O(4)) molecules are linked with O(2) and O(1) by hydrogen bonds with bond lengths 2.900(1) and 2.999(1)? respectively.

Synthesis and Crystal Structure of (Z)-Ethyl-4-(4-methoxy)benzylidene-2-(3,5-dimethoxypheny-tetrahydrofuran-3,3-dicarboxylate

The title compound （Z）-ethyl-4-（4-methoxy）benzylidene-2-（3,5-dimethoxyphenyl）- tetrahydrofuran-3,3-dicarboxylate has been synthesized, and its crystal structure was characterized by X-ray single-crystal diffraction. The crystal belongs to triclinic, space group P1, with a = 8.140（3）, b = 11.966（4）, c = 13.771（5）Aα= 67.366（4）, β= 85.165（5）, γ= 75.806（4）°, V = 1200.1（7） A3, Z = 2, C26H3008, Mr = 470.50, Dc = 1.302 g/cm^3, F（000） = 500,λ（MoKa） = 0.71073 A, μ= 0.096 mm^-1, R = 0.0659 and wR = 0.1841 for 3080 observed reflections （I 〉 2σ（I））. As a key intermediate of HIV-1 integrase inhibitor, the synthesis and structure confirmation of the title compound are important for further studies.

Synthesis, Crystal Structure and Antimicrobial Activity of (E)-ethyl-4-(2-oxoacenaphthylen-1(2<i>H</i>)-ylideneamino) benzoate

A Schiff base, (E)-ethyl-4-(2-oxoacenaphthylen-1(2H)-ylideneamino)benzoate, (E4AB) had been synthesized in good yield by the acid-catalyzed condensation reaction of acenaphthenequinone and ethyl-4-aminobenzoate in methanolic solution. The synthesized compound was elucidated by elemental analysis (CHN), FTIR, 1H-NMR, 13C-NMR and single crystal X-ray diffraction. E4AB crystallized in the monoclinic crystal system with space group P21/c, Z = 4, V = 1569.3(2) ?3 and unit cell parameters a = 9.1589(8) , b = 21.2003(17)?, c =8.4502(7) ?, β= 106.972(2)°. The crystal structure of the compound is stabilized by intermolecular C-H···O hydrogen bonds and weak intermolecular π···π interactions. The title compound had been tested for the antimicrobial activity against Bacillus subtilis (B. subtilis), Enterobacter and Fusarium oxysporum f. sp. Cubense (Foc) by disc-diffusion method. E4AB is relatively active against Foc which is a pathogen that cause Wilt disease (also well known as Panama disease) in banana plantation.

杯[4]芳烃四噻吩衍生物的合成

以杯[4]芳烃为底物,与氯乙酸乙酯在碱性条件下反应合成了杯[4]芳烃四乙酸乙酯,经水解后与二氯亚砜反应得到杯[4]芳烃四乙酰氯,再与噻吩甲胺反应后成功合成了杯[4]芳烃四噻吩衍生物,并利用^(1)H NMR、IR确认了目标产物的结构。

4-氨基-2,6-二甲氧基嘧啶合成研究进展

4-氨基-2,6-二甲氧基嘧啶是制备抗菌药物磺胺地索辛的关键中间体,磺胺地索辛是一种长效磺胺类药物,具有很强的抗细菌及抗原虫感染作用。本文主要综述4-氨基-2,6-二甲氧基嘧啶的合成方法。

阿加曲班中间体(2R,4R)-4-甲基-2-哌啶甲酸乙酯合成工艺研究

阿加曲班系合成的左旋精氨酸的哌啶羧酸衍生物,属于抗凝药,在文献研究的基础上,对阿加曲班中间体的合成工艺进行了优化,包括化合物4-甲基-2-哌啶甲酸盐酸盐、4-甲基-2-哌啶甲酸乙酯、4-甲基-2-哌啶甲酸乙酯对甲苯磺酸盐、(2R,4R)-4-甲基-2-哌啶甲酸乙酯对甲苯磺酸盐及(2R,4R)-4-甲基-2-哌啶甲酸乙酯等的制备。本文选用对甲苯磺酸代替L-酒石酸作为手性拆分试剂,并且对拆分得到的其他构型的4-甲基-2-哌啶甲酸乙酯进行消旋回收。利用合理的反应条件,优化后的合成工艺,可节省原料,缩短反应时间,提高反应收率,为工业化生产提供实验依据。

微流控制备包覆含能材料模拟物的核壳结构微球

基于简单的生产单重乳液的液滴微流控技术,结合相分离和结晶固化的方法,制备出具有对硝基苯甲醛(p-NBA)核层和聚苯乙烯(PS)壳层的核壳结构微球,一步完成了对高能炸药3,4-二硝基呋咱基氧化呋咱(DNTF)的模拟物p-NBA的包覆;通过调控p-NBA、PS以及赋形剂乙基纤维素(EC)的含量配比,可以得到不同结构和形貌的微球,并研究了上述因素对核壳结构微球的影响;基于高能炸药DNTF的包覆钝化效果和包覆量双重条件,在使用大相对分子质量(M r=300000~350000)PS情况下,得出最佳实验条件为:EC和p-NBA质量比为1∶10,PS质量分数为8%。结果表明,赋形剂的添加有助于促进p-NBA的结晶,使其能够在液滴相分离的时候形成球形颗粒,从而被完整包覆;PS在微液滴中的初始质量分数越大,形成的壳层越厚、球形度越高,但封装DNTF的壳层越厚,爆炸威力会降低。

The Amperometric Glucose Enzyme Electrode by Immobilized Glucose Oxidase in Glucose Oxidase/N-ethyl-Poly (4-vinyl)pyridine Multilayer

Multilayers of glucose oxidase(GOD)/N-ethyl-poly (4-vinyl) pyridine (EPVP) have been assembled on thiol self-assembled monolayers on gold electrode.This electrode can be used as an amperometric enzyme elcctrode for glucose. Fe (CN)63-/4- incorporated in EPVP layer acts as the electron mediator, the linear range was 0.1 to 6 mmol/L when the number of GOD layers was 5.

唑草酮中间体2-(4-氯-2-氟苯基)-5-甲基-1H-1,2,4-三唑-3-酮的合成

为了提高唑草酮关键中间体2-(4-氯-2-氟苯基)-5-甲基-1H-1,2,4-三唑-3-酮的产品质量,提升反应收率并降低成本,以4-氯-2-氟苯肼为原料,利用一锅法合成工艺,经脱水缩合、1,3-偶极加成和氧化脱氢反应,得到2-(4-氯-2-氟苯基)-5-甲基-1H-1,2,4-三唑-3-酮。通过筛选反应参数,得到最佳合成条件为:以乙醇-水(质量比4∶1)为溶剂,醋酸作为质子酸,4-氯-2-氟苯肼、乙醛、氰酸钠、醋酸、次氯酸钠的摩尔比为1.0∶1.5∶1.5∶1.6∶1.6,反应温度15℃。采用HPLC进行反应中控,以^(1)H-NMR、^(13)C-NMR、ESI-MS等对产物进行表征,结果显示产物为目标产物,HPLC纯度≥99%,收率为90%。该一锅法合成工艺,操作简便,设备利用率高,节约能耗和工时,适合工业化生产,对类似唑草酮中间体的化合物生产工艺设计具有借鉴意义。

2-[(2-乙基-5-氟苯并呋喃-3-基)甲基]-4-甲基-5-噻唑甲酸合成路线的改进

在课题组前期2-[(2-乙基-5-氟苯并呋喃-3-基)甲基]-4-甲基-5-噻唑甲酸合成路线的基础上进行改进,以5-氟水杨醛为起始原料,经环合、还原、亲电取代、硫代、环合、水解反应得到目标化合物,化合物结构经^(1)HNMR、^(13)CNMR和HRMS确证。与原合成路线相比,该路线减少了合成步骤,目标化合物总收率由0.3%提高到5.0%。