Direct ortho‐Hydroxylation of 2‐Phenylpyridines using Palladium(II) Chloride and Hydrogen Peroxide

Direct functionalization of the ubiquitous C H bond is receiving much attention because complex structures can be formed from simple precursors. This paper reports a useful method for the direct hydroxylation of 2‐phenylpyridines using palladium(II) chloride and aqueous hydrogen peroxide. In this method, hydrogen peroxide, which has high atom efficiency, is employed as the oxidant and phenol derivatives are generated via C H activation.

     

对苯二酚的合成与应用研究进展

介绍了对苯二酚的应用,叙述了其各种有机与电化学合成工艺,指出了各种工艺的优缺点,展望对苯二酚合成研究前景.认为有机电合成工艺是制备对苯二酚最具潜力的方法.     

Changing the regioselectivity of a P450 from C15 to C11 hydroxylation of progesterone

CYP106A2 is known as a 15β‐hydroxylase, but also shows minor 11α‐hydroxylase activity for progesterone. 11α‐Hydroxyprogesterone is an important pharmaceutical compound with anti‐androgenic and blood‐pressure‐regulating activity. This work therefore focused on directing the regioselectivity of the enzyme towards hydroxylation at position 11 in the C ring of the steroid through a combination of saturation mutagenesis and rational site‐directed mutagenesis. With the aid of data from a homology model of CYP106A2 containing docked progesterone, together with site‐directed mutagenesis of active‐site residues (Lisurek et al. ChemBioChem 2008 , 9, 1439–1449), a saturation mutagenesis library at positions A395 and G397 was created. Screening of the library identified the mutants A395I and A395W/G397K as having 11α‐hydroxylase activities 8.9 and 11.5 times higher than that of the wild type (WT). In the next step, additional mutations were integrated by a rational site‐directed mutagenesis approach to increase the catalytic efficiency. Of the 40 candidates analyzed, the mutants A106T/A395I, A106T/A395I/R409L, and T89N/A395I turned out to display increased 11α‐hydroxylase selectivities and activities relative to the WT (14.3‐, 12.6‐, and 11.8‐fold increases in selectivity and 39.3‐, 108‐, and 24.4‐ in k_cat/K_m). In the last step of the study, the best mutants were applied in a whole‐cell biotransformation. In these experiments the production (percentage) of 15β‐hydroxyprogesterone decreased from 50.4 % (wild type) to 4.8 % (mutant T89N/A395I), whereas that of 11α‐hydroxyprogesterone increased from 27.7 to 80.9 %, thus demonstrating an impressive regioselectivity.     

Efficient Room‐Temperature Oxidation of Hydrocarbons Mediated by Tricopper Cluster Complexes with Different Ligands

Six tricopper cluster complexes of the type [Cu^ICu^ICu^I( L )]¹⁺ supported by a series of multidentate ligands ( L ) have been developed as oxidation catalysts. These complexes are capable of mediating the facile oxygen‐atom transfer to hydrocarbon substrates like cyclohexane, benzene, and styrene (C₆H₁₂, C₆H₆ and C₈H₈) upon activation by hydrogen peroxide at room temperature. The processes are catalytic with high turnover frequencies (TOF), efficiently oxidizing the substrates to their corresponding alcohols, aldehydes, and ketones in moderate to high yields. The catalysts are robust with turnover numbers (TON) limited only by the availability of hydrogen peroxide used to drive the catalytic turnover. The TON is independent of the substrate concentration and the TOF depends linearly on the hydrogen peroxide concentration when the oxidation of the substrate mediated by the activated tricopper complex is rapid. At low substrate concentrations, the catalytic system exhibits abortive cycling resulting from competing reduction of the activated catalyst by hydrogen peroxide. This behaviour of the system is consistent with activation of the tricopper complex by hydrogen peroxide to generate a strong oxidizing intermediate capable of a facile direct “oxygen‐atom” transfer to the substrate upon formation of a transient complex between the activated catalyst and the substrate. Some substrate specificity has also been noted by varying the ligand design. These properties of the tricopper catalyst are characteristic of many enzyme systems, such as cytochrome P450, which participate in biological oxidations.     

芬顿试剂羟基化苯制苯酚反应的研究进展

评述了芬顿试剂羟基化苯制苯酚反应的研究进展，重点讨论了反应机理和芬顿试剂的改进。     

甲醇-水体系中苯羟基化制苯酚的研究

多步法合成苯酚中需加入酸及有机试剂,容易造成环境污染。在TS-1分子筛与过氧化氢形成的体系中苯一步羟基化合成苯酚的方法,由于反应条件温和,绿色环保,引起了研究者的关注,但目前的文献报道都基于单一溶剂体系,研究结果各有差异。在甲醇-水两元混合体系中,通过改变两者比例来调整溶液极性,采用TS-1分子筛为催化剂,双氧水为氧化剂,研究了TS-1分子筛直接催化苯羟基化制苯酚的反应。结果表明,当n(水)∶n(甲醇)=0.78、反应时间4h、催化剂用量TS-1/苯为17.5g/mol、n(过氧化氢)∶n(苯)=4.76、反应温度为60℃,苯酚的收率在甲醇-水体系中明显优于单一溶剂,并在此条件下,加入冰醋酸量为n(冰醋酸)∶n(苯)=0.31时,苯酚收率可达12.82%。     

二乙胺羟基化合成二乙基羟胺

以改性的TS-1分子筛为催化剂,研究了二乙胺与过氧化氢羟基化的工艺路线。考察了原料配比、反应时间、反应温度等因素对反应的影响,特别是溶剂对反应的重要性。实验表明,反应的最佳条件为:H2O2与二乙胺的物质的量比为1.0~1.1,反应温度75~80℃,反应时间70 min,催化剂浓度4%,叔丁醇-水作为混合溶剂,叔丁醇与水的体积比为2~2.5;H2O2有效转化率88.2%,二乙基羟胺的选择性达到80.1%。     

苯酚羟基化合成二酚催化剂的研究进展

邻苯二酚和对苯二酚都是重要的化工原料和中间体.在催化剂作用下,以H2O2为氧化剂,苯酚羟基化合成二酚是一条反应条件温和、环境友好的合成路线.介绍了二酚的生产现状,综述了苯酚羟基化合成二酚反应中的催化剂的研究进展,并讨论了它们的制备、性能和应用前景.     

Ni对Cu-Ni/γ-Al_2O_3苯羟基化催化剂的影响

通过程序升温还原方法合成了Cu/γ-Al2O3和Cu-Ni/γ-Al2O3催化剂,使苯直接羟基化制苯酚。该反应过程中,温度和溶剂对Cu-Ni/γ-Al2O3催化剂的反应性能影响进行了探讨。采用H2-TPR、XRD、EDS等表征技术考察了Ni对催化剂结构和性质的影响。结果表明,Ni使催化剂前驱体还原温度增加、活性组分Cu单晶粒度降低、催化剂表面Cu原子数增加;当反应温度为70°C、以水作反应溶剂时,Cu-Ni/γ-Al2O3比Cu/γ-Al2O3催化剂有较高反应活性和选择性,苯转化率为32.4%,苯酚选择性为93.3%,苯酚收率为30.2%。