3182-95-4Relevant articles and documents
Effects of the preparation method on the performance of the Cu/ZnO/Al 2O3 catalyst for the manufacture of l-phenylalaninol with high ee selectivity from l-phenylalanine methyl ester
Shi, Zhangping,Xiao, Xiuzhen,Mao, Dongsen,Lu, Guanzhong
, p. 1132 - 1143 (2014)
The effects of the preparation method on the properties of Cu/ZnO/Al 2O3 catalysts for l-phenylalanine methyl ester hydrogenation to l-phenylalaninol were investigated in detail, including the precipitation method and conditions (the aging time, calcination temperature and so on), with the help of ICP-OES, N2 and N2O adsorption, XRD, H2-TPR and TEM techniques. The results show that physicochemical properties of the catalysts are greatly affected by the preparation method and conditions. The uniform size distribution of CuO species can be obtained by fractional co-precipitation. The appropriate aging time is 2 h, and the catalyst aged for 2 h has the largest metallic copper surface area (SCu) and surface copper amount and the smallest CuO crystallites. The lower calcination temperature is favorable for increasing the surface area and metallic copper surface area of the catalyst. The spinel structure CuAl2O4 phase can form after calcination at 550 °C. The turnover frequency (TOF) values of l-phenylalaninol formed using different catalysts indicate the structurally sensitive character of the title reaction, and SCu is not the sole cause affecting the catalytic activities of the catalysts. B-TOF on the basis of the active sites (Cu0) in the boundary between CuO and ZnO or Al2O3 was proposed; the relationships of B-TOF with dCuO (particle size of CuO) and SCu were established. Using the Cu/ZnO/Al2O3 catalyst prepared by fractional co-precipitation with aging at 70 °C for 2 h and calcination at 450 °C for 4 h, 83.6% selectivity to l-phenylalaninol without racemization was achieved. This journal is the Partner Organisations 2014.
Enantioselective Synthesis of β-Hydrazino Alcohols Using Alcohols and N-Boc-Hydrazine as Substrates
Cui, Zhihao,Du, Da-Ming
, p. 5616 - 5619 (2016)
An enantioselective approach for the synthesis of α-hydrazino aldehydes is described that utilizes alcohols and N-Boc hydrazine instead of the conventional combination of aldehydes with azodicarboxylates. This protocol is enabled by merging in situ aerobic dual oxidation with asymmetric organocatalysis. This reaction also exhibits a high tolerance for varieties of substituents on the alcohol component. This approach features excellent enantiocontrol, cheap starting materials, operational simplicity, and scalability. The corresponding chiral β-hydrazino alcohols were obtained by sequential reduction with excellent enantioselectivity (up to 98% ee).
Preparation of L-phenylalaninol with high ee selectivity by catalytic hydrogenation of L-phenylalaninate over Cu/ZnO/Al2O3 catalyst
Gao, Chunyou,Xiao, Xiuzheng,Mao, Dongsen,Lu, Guanzhong
, p. 1056 - 1062 (2013)
The Cu/ZnO/Al2O3 catalyst for hydrogenation of l-phenylalaninate to l-phenylalaninol was prepared by a co-precipitation method, and characterized by XRD, low-temperature N2 adsorption, H 2-TPR, N2O chemisorption and ICP-AES. The results show that the physicochemical properties of the catalyst are greatly affected by the ZnO amount, and that the exposed copper surface area, dispersion of CuO and BET surface area of the Cu/ZnO/Al2O3 catalyst (Cu/Zn/Al = 1.0:0.3:1.0) reach the largest. The chemoselectivity of l-phenylalaninol is changed with ZnO amount in the Cu/ZnO/Al2O3 catalyst, and when Cu/Zn/Al = 1.0:0.3:1.0, the catalyst exhibits higher catalytic performance and chemoselectivity to l-phenylalaninol. Furthermore, the effect of temperature, pressure, reaction time and the molar ratio of catalyst to ester on the catalytic hydrogenation of l-phenylalaninate were investigated. When the catalytic hydrogenation of l-phenylalaninate was operated at 110 °C and 4 MPa of H2 for 5 h, the yield of l-phenylalaninol can reach 69.2 %, and its ee selectivity is 99.84 %.
A highly effective and stable CuZn0.3MgxAlOy catalyst for the manufacture of chiral l-phenylalaninol: The role of Mg and its hydrotalcite-like precursor
Shi, Zhangping,Zhang, Shuangshuang,Xiao, Xiuzhen,Mao, Dongsen,Lu, Guanzhong
, p. 3457 - 3467 (2016)
Highly effective CuZn0.3MgxAlOy (x = 0-0.2) catalysts for the synthesis of chiral l-phenylalaninol derived from Cu-rich hydrotalcite-like precursors were prepared by a co-precipitation method with Na2CO3 as the precipitant, and their physicochemical and catalytic properties were characterized. The results show that the presence of Mg2+ ions can promote the formation of hydrotalcite-like (htl) precursors, and the Mg2+ content would affect the phase purity of the prepared htl precursors. The BET surface area, exposed copper surface area and amount of acid sites of the samples decreased with the increase in the molar ratio of Mg2+/Al3+. Also, the dense layered htl precursors are beneficial to the atomically uniform distribution of the corresponding metal oxides in the prepared catalysts, promoting the stronger interaction between Cu0 and Al2O3 after the catalysts were reduced (SMSI effect). The activity of the CuZn0.3MgxAlOy catalysts is greatly dependent on not only the metallic copper surface area, but also the SMSI effect and the acidity of the catalysts. When Mg2+/Al3+ = 0.1 (mol), a phase-pure htl precursor could be obtained, and after calcination, the prepared CZA-0.1 catalyst exhibited very excellent catalytic performance for the hydrogenation of l-phenylalanine methyl ester to chiral l-phenylalaninol. After 5 h of reaction at 110 °C and 4 MPa H2, 100% conversion of l-phenylalanine methyl ester and 91.1% yield of l-phenylalaninol with an ee value of ～100% were achieved. After recycling 13 times, the l-phenylalaninol selectivity of the CZA-0.1 catalyst only decreased by 7.2%.
Chemical development on the chiral auxiliary (S)-4-(phenylmethyl)-2-oxazolidinone utilizing automated synthesis and DoE
Vo, Lanchi,Ciula, James,Gooding, Owen W.
, p. 514 - 520 (2003)
Enantiopure 4-substituted oxazolidinones are well-known chiral auxiliaries for asymmetric synthesis of carboxylic acid derivatives. The 4-(phenylmethyl)-substituted oxazolidinones derived from D- or L-phenylalanine are known to be particularly useful. We have conducted chemical development studies toward an efficient and scaleable "one-pot" process for production of (S)-4-(phenylmethyl)-2-oxazolidinone 2. The first step in the process employed a sodium borohydride reduction of phenylalanine mediated by an additive. The second step utilized triphosgene as a phosgene source to effect cyclization of the intermediate amino alcohol. Both chemical steps and workup procedures were screened and optimized utilizing statistical design of experiments (DoE) and parallel synthesis. The procedure was further characterized in an automated reactor system that provided heat flow measurements and modeled production at the plant scale. The efficiency of this process was compared to those of others previously reported on the basis of raw material cost, time requirements, safety, and hazardous waste generation.
Construction and activity evaluation of novel benzodioxane derivatives as dual-target antifungal inhibitors
An, Yunfei,Fan, Haiyan,Han, Jun,Liu, Wenxia,Sun, Bin,Xie, Honglei
, (2021/11/09)
Ergosterol exert the important function in maintaining the fluidity and osmotic pressure of fungal cells, and its key biosynthesis enzymes (Squalene epoxidase, SE; 14 α-demethylase, CYP51) displayed the obvious synergistic effects. Therefore, we expected to discover the novel antifungal compounds with dual-target (SE/CYP51) inhibitory activity. In the progress, we screened the different kinds of potent fragments based on the dual-target (CYP51, SE) features, and the method of fragment-based drug discovery (FBDD) was used to guide the construction of three different series of benzodioxane compounds. Subsequently, their chemical structures were synthesized and evaluated. These compounds displayed the obvious biological activity against the pathogenic fungal strains. Notably, target compounds 10a-2 and 22a-2 possessed the excellent broad-spectrum anti-fungal activity (MIC50, 0.125–2.0 μg/mL) and the activity against drug-resistant strains (MIC50, 0.5–2.0 μg/mL). Preliminary mechanism studies have confirmed that these compounds effectively inhibited the dual-target (SE/CYP51) activity, they could cause fungal rupture and death by blocking the bio-synthetic pathway of ergosterol. Further experiments discovered that compounds 10a-2 and 22a-2 also maintained a certain of anti-fungal effect in vivo. In summary, this study not only provided the new dual-target drug design strategy and method, but also discover the potential antifungal compounds.
Preparation method of oxazolidinone compound
-
Paragraph 0044; 0047-0048, (2021/11/10)
The preparation method comprises the following steps 1): dissolving aromatic amino acid in methanol, dissolving the aromatic amino acid in methanol, heating up to 50 - 60 °C heat preservation 1 - 2h, 2) reducing: adding a catalytic amount of lithium salt in ethanol water as a solvent. 3) Ring-closing: toluene is used as a solvent, a reduction product and diethyl carbonate are added to 100 °C, a sodium methoxide solution is added dropwise, and the product is obtained after completion of the dropwise addition and after-treatment and purification after completion of the normal pressure distillation to the temperature of 100 °C heat preservation. The lithium salt is introduced to participate in the reaction, sodium borohydride is selected as a solvent, sodium borohydride is completely dissolved, and the lithium salt can be free from the compound to improve the reaction activity, so that the use amount of sodium borohydride is reduced to 2 equivalent, and the production cost is remarkably reduced.
Direct Access to Primary Amines from Alkenes by Selective Metal-Free Hydroamination
Du, Yi-Dan,Chen, Bi-Hong,Shu, Wei
supporting information, p. 9875 - 9880 (2021/03/29)
Direct and selective synthesis of primary amines from easily available precursors is attractive yet challenging. Herein, we report the rapid synthesis of primary amines from alkenes via metal-free regioselective hydroamination at room temperature. Ammonium carbonate was used as ammonia surrogate for the first time, allowing for efficient conversion of terminal and internal alkenes into linear, α-branched, and α-tertiary primary amines under mild conditions. This method provides a straightforward and powerful approach to a wide spectrum of advanced, highly functionalized primary amines which are of particular interest in pharmaceutical chemistry and other areas.
Nucleophilic RhI Catalyzed Selective Isomerization of Terminal Aziridines to Enamides
Tian, Yingying,Kunz, Doris
, p. 4272 - 4275 (2020/07/04)
The selective isomerization of various terminal N-Boc protected aziridines to enamides was realized using the highly reactive nucleophilic rhodium catalyst C with the Lewis acid LiNTf2 as co-catalyst under moderate conditions. The reaction proceeds smoothly with only 1 molpercent catalyst loading and excellent yields were achieved. An intermediate containing an enamide with a non-conjugated terminal C=C double bond was detected during the course of the reaction, which isomerizes to form the thermodynamically favored 2-amido styrene. Mechanistic insight is gained based on these observations.
Nascent-HBr-Catalyzed Removal of Orthogonal Protecting Groups in Aqueous Surfactants
Bera, Smritilekha,Gupta, Shilpi,Mondal, Dhananjoy
, (2020/02/04)
Organic reactions in the aqueous environment have recently emerged as a promising research area. The generation of nascent-HBr from the slow hydrolysis of the dispersed catalyst, benzyl bromide, with the interior water present in the hydrophobic core of the confined micellar medium in aqueous surfactant is described for the first time. The sustained-release nascent-HBr enabled the chemoselective cleavages of acid-sensitive orthogonal functionalities present in carbohydrates, amino alcohols, and hydroxylated acyclic compounds in good to excellent yields.
