瑞德西韦中间体2-乙基丁醇的合成工艺研究

介绍了瑞德西韦的关键中间体2-乙基丁醇(1)的新合成工艺。以丙二酸二甲酯为起始原料,在碱性条件下和溴乙烷反应得到中间体二乙基丙二酸二甲酯,然后进行水解和脱酸反应得到2-乙基丁酸,2-乙基丁酸在氢气的环境中,在均相催化剂三(乙酰丙酮酸)钌(Ⅲ)、配体TRIPHOS(1,1,1-三(二苯基膦甲基)乙烷)的作用下,还原得到目标化合物2-乙基丁醇(1)。与目前公开的路线相比,本工艺操作简便,原料价廉易得,各步收率高,适合工业化生产。

Solid-Liquid Equilibria of trans-1,2-Cyclohexanediol＋Butyl Acetate＋ Water Ternary System

Using a laser observation technique,the solubilities of trans-1,2-cyclohexanediol in butyl acetate+wa- ter were measured at the temperature range from 298.15K to 323.15K by a synthetic method at atmospheric pres- sure.It is shown that the solubilities of trans-1,2-cyclohexanediol in butyl acetate+water were affected greatly by the proportion of butyl acetate and water,and presented maximum value at given temperature.The UNIFAC model was used to correlate the experimental data.The average relative deviation(ARD)between experimental and calculated values is 3.03%.

Electronic and steric factors for enhanced selective synthesis of 2‐ethyl‐1‐hexanol in the Ir‐complex‐catalyzed Guerbet reaction of 1‐butanol

1‐Butanol is a potential bio‐based fermentation product obtained from cellulosic biomass.As a value‐added chemical,2‐ethyl‐1‐hexanol(2‐EH)can be produced by Guerbet conversion from 1‐butanol.This work reports the enhanced catalytic Guerbet reaction of 1‐butanol to 2‐EH by a series of Cp^(*)Ir complexes(Cp^(*):1,2,3,4,5‐pentamethylcyclopenta‐1,3‐diene)coordinated to bipyridine‐type ligands bearing an ortho‐hydroxypyridine group with an electron‐donating group and a Cl−anion.The catalytic activity of the Cp^(*)Ir complex increased by increasing the electron density of the bipyridine ligand when functionalized with the para‐NMe2 and ortho‐hydroxypyridine groups.A record turnover number of 14047 was attained.A mechanistic study indicated that the steric effect of the ethyl group on theα‐C of 2‐ethylhexanal(2‐EHA)and the conjugation effect of C=C–C=O in 2‐ethylhex‐2‐enal(2‐EEA)benefits the high selectivity of 2‐EH from 1‐butanol by inhibiting the cross‐aldol reaction of 2‐EHA and 2‐EEA with butyraldehyde.Nuclear magnetic resonance study revealed the formation of a carbonyl group in the bipyridine‐type ligand via the reaction of the Cp^(*)Ir complex with KOH.

Porous alumina ceramic via gelcasting based on2-hydroxyethyl methacrylate dissolved in tert-butyl alcohol

To obtain porous alumina ceramic with high strength,a novel gelcasting system based on 2-hydroxyethyl methacrylate(HEMA)dissolved in tert-butyl alcohol(TBA)was developed.The polymerization of the HEMA-TBA gelcasting system,the thermal behavior of obtained green body,and the microstructures and mechanical properties of the sintered bodies were investigated by rheometer,TG-DSC,SEM and bending strength testing,respectively.The results show that,(1)10 mg/mL of the initiator(benzoyl peroxide)is the optimal amount for polymerization of this gelscasting system at 25 ℃;(2)The alumina suspension of the HEMA-TBA gelcasting system showing shear-thinning behavior is sufficiently low for gelcasting process;(3)The bending strength of porous alumina ceramic samples,whose porosities range from 42% to 56%,is from(8±0.5)to(91±4.5)MPa.

Phase Transfer Catalysis: Oxidation of 2-Methyl-1-butanol

In liquid-liquid systems, the substrates in the liquids are inaccessible to each other for the reaction. By adding a small quantity of phase transfer catalyst, the reaction can be made accessible and accelerated. The present study involves the phase transfer catalyzed oxidation of 2-methyl-l-butanol by quaternary ammonium permanganate （tricaprylyl methyl ammonium permanganate）. The attempt was to compare the kinetics under homogeneous and heterogeneous conditions. Experiments were conducted in a batch reactor to determine the kinetics under homogeneous conditions. A baffled horosilicate agitated reactor was used to find the enhancement factor and the kinetics under heterogeneous conditions. The rate constants determined under both homogeneous and heterogeneous conditions agreed very weU. The oxidation was found to be first order with respect to each of the reactants, quaternary ammonium permanganate and the alcohol, resulting in an overall second order rate expression. Aliquat336 （tricaprylylmethylammonium chloride） was found to be the best compared with the other catalysts tested （triethylbenzylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium iodide and tetrabutylammonium hydrogen sulfate） and it gave an enhancement factor of 9.8.

气相色谱法测定2-乙基丁醛中7个杂质的含量

目的:建立气相色谱法(GC)测定2-乙基丁醛中乙醛、丁醛、巴豆醛、丁醇、2-乙基丁醇、2-乙基丁酸和三聚乙醛的含量。方法:采用100%二甲基聚硅氧烷为固定液的毛细管柱(DB-1,0.53 mm×30 m,3μm),起始温度为60℃,维持2 min,以5℃·min^(-1)的速率升温至120℃,维持15.5 min,进样口温度为200℃,氢火焰离子化检测器(FID)温度为260℃,载气为氮气,分流比为40∶1,进样体积1μL,外标法定量。结果:乙醛、丁醛、巴豆醛、丁醇、2-乙基丁醇、2-乙基丁酸、三聚乙醛的质量浓度分别在0.1001~0.3004 mg·mL^(-1)(r=0.9991)、0.2005~0.6015 mg·mL^(-1)(r=0.9994)、0.0255~0.0766 mg·mL^(-1)(r=0.9993)、0.1066~0.3017 mg·mL^(-1)(r=0.9993)、0.1002~0.3006 mg·mL^(-1)(r=0.9985)、0.2501~5.0016 mg·mL^(-1)(r=1.000)、0.0808~2.4233 mg·mL^(-1)(r=0.9993)范围内,峰面积与之呈良好线性关系;平均回收率分别为107.4%、106.9%、100.4%、109.1%、101.8%、103.8%、104.1%,RSD分别为1.1%、1.5%、1.2%、1.9%、1.6%、5.2%、0.50%;3批样品中乙醛、丁醛、巴豆醛、丁醇、2-乙基丁醇、2-乙基丁酸和三聚乙醛含量分别在0.02%~0.31%、0.57%~1.0%、0.01%~0.02%、0.24%~0.33%、未检出~0.25%、2.2%~3.9%、0.66%~1.9%范围内。结论:本试验建立的分析方法分离度好,结果准确,可有效分离并测定2-乙基丁醛中7个杂质的含量,为其质量控制提供保障。

Thermal and photoinduced valence tautomerism of a chain compound

Herein reported is an example of one-dimensional coordination polymer [Co11(3,5-DBsq)2(dpg)]·(3,5-H2DBcat)2 (1) (3,5-DBsq = 3,5-di-tert-butylsemiquinonate, 3,5-H2DBcat = 3,5-di-tert-butyl-benzene-1,2-diol, dpg = meso-alpha,beta-di(4-pyridyl)glycol) capable of undergoing thermal and photoinduced valence tautomeric transitions.