Convenient synthesis of oxazolidinones by the use of halomethyloxirane, primary amine, and carbonate salt

[reaction: see text] Primary amines reacted with carbonate salts (Na2CO3, K2CO3, Cs2CO3, and Ag2CO3) and halomethyloxiranes in the presence of a base such as DBU or TEA to give oxazolidinones in high yields. The use of K2CO3 among these carbonate gave the best yield in this synthesis. A reaction mechanism was proposed that the oxazolidinone was obtained from an oxazinanone intermediate via a bicyclo[2.2.1] intermediate. The present reaction can be widely applied to convenient synthesis of useful N-substituted oxazolidinones and chiral oxazolidinones.     

微波法合成2-羟乙基苯并[d]异噻唑-3(2H)-酮

以苯并异噻唑-3(2H)-酮(BIT)及氯乙醇为原料微波法合成了2-羟乙基苯并[d]异噻唑-3(2H)酮。考察了氢氧化钠量,氯乙醇用量,反应时间,反应温度对反应的影响,经正交实验设计得到了最佳反应条件,最佳反应条件下收率为83.3%。结果表明,与传统工艺相比,微波技术合成2-羟乙基苯并[d]异噻唑-3(2H)-酮的方法具有操作方便、收率高等特点,具有一定的应用价值。     

固体碱在二氧化碳-甲醇法合成碳酸二甲酯反应中的作用

本文探讨了固体碱的制备和预处理等因素对于ＣＯ_２~－甲醇法合成碳酸二甲酯（ＤＭＣ）的影响,发现微波法所制碱性沸石等多孔材料的反应活性高于浸渍法所制样品。本文首次报道了微波辐射低压合成ＤＭＣ的新方法,该法能极大地缩短反应时间并提高产物选择性。研究表明： ＣＯ_２和甲醇生成 ＤＭＣ的反应在热力学上是几乎不能进行的,加入固体碱的实质是提供了一条耦合的途径。     

3-氨基-4-硝基氧化呋咱含能化合物的设计合成研究

在氧化呋咱环上引入氨基或硝基等功能基团,可提高含能化合物的能量密度和爆炸性能。为了获得更高能量密度的新型含能化合物,本文利用密度泛函理论（DFT）和单、双激发的耦合簇（CCSD）方法探索了以3-酰基叠氮基-4硝基氧化呋咱为起始材料,在二氧六环和水混合溶剂中合成3-氨基-4硝基氧化呋咱的反应机理,给出了反应的势能曲线。结果表明,该反应主要分为两个阶段：3-酰基叠氮基-4硝基氧化呋咱脱N₂后进行Curtious重排产生异氰酸酯;异氰酸酯经水解、羟基扭转、CO₂的脱离形成产物。反应的决速步为CO₂的脱离,能垒为44kcal/mol。因此,加热是实现该合成反应的必要条件。水既绿色环保,又参与反应,是该反应的最佳溶剂。这些结果为3-氨基-4-硝基氧化呋咱的实验合成提供了必要的理论依据。     

正交法研究六氯环三磷腈的合成

利用正交法研究了六氯环三磷腈的合成反应;针对较典型的四个因素,分别取四水平L16(45)正交表进行正交试验,确定了合成目标产物的主要影响因素和优化反应条件.结果表明,先将2/3的固体五氯化磷与2%无水氯化锌和30%吡啶(以五氯化磷物质的量计)混合,再缓慢滴加入剩余的五氯化磷氯苯溶液,最高产率可达84%以上;方差分析结果...     

Theoretical study on the mechanism of reaction between 3-hydroxy-3-methyl-2-butanone and malononitrile catalyzed by lithium ethoxide

The The mechanism of reaction between 3-hydroxy-3-methyl-2-butanone and malononitrile for the synthesis of 2-dicyanomethylene-4, 5, 5-trimethyl-2,5-dihydrofuran-3-carbonitrile catalyzed by lithium ethoxide was investigated by density functional theory (DFT). The geometries and the frequencies of reactants, intermediates, transition states and products were calculated at the B3LYP/6-31G(d) level. The vibration analysis and the IRC analysis verified the authenticity of transition states. The reaction processes were confirmed by the changes of charge density at the bond-forming critical point. The results indicated that lithium ethoxide is an effective catalyst in the synthesis of 2-dicyanomethylene-4, 5, 5-trimethyl-2, 5-dihydrofuran-3-carbonitrile from malononi-trile and 3-hydroxy-3-methyl-2-butanone. The activation energy of the reaction with lithium ethoxide was 115.86 kJ·mol⁻¹ less than the uncatalyzed reaction. The mechanism of the lithium ethoxide catalyzed reaction differed from the mechanism of the uncatalyzed reaction.     

Development of high performance Cu/ZnO-based catalysts for methanol synthesis and the water-gas shift reaction

Our groups studies on Cu/ZnO-based catalysts for methanol synthesis via hydrogenation of CO₂ and for the water-gas shift reaction are reviewed. Effects of ZnO contained in supported Cu-based catalysts on their activities for several reactions were investigated. The addition of ZnO to Cu-based catalyst supported on Al₂O₃, ZrO₂ or SiO₂ improved its specific activity for methanol synthesis and the reverse water-gas shift reaction, but did not improve its specific activity for methanol steam reforming and the water-gas shift reaction. Methanol synthesis from CO₂ and H₂ over Cu/ZnO-based catalysts was extensively studied under a joint research project between National Institute for Resources and Environment (NIRE; one of the former research institutes reorganized to AIST) and Research Institute of Innovative Technology for the Earth (RITE). It was suggested that methanol should be produced via the hydrogenation of CO₂, but not via the hydrogenation of CO, and that H₂O produced along with methanol should greatly suppress methanol synthesis. The Cu/ZnO-based multicomponent catalysts such as Cu/ZnO/ZrO₂/Al₂O₃ and Cu/ZnO/ZrO₂/Al₂O₃/Ga₂O₃ were highly active for methanol synthesis from CO₂ and H₂. The addition of a small amount of colloidal silica to the multicomponent catalysts greatly improved their long-term stability during methanol synthesis from CO₂ and H₂. The purity of the crude methanol produced in a bench plant was 99.9 wt% and higher than that of the crude methanol from a commercial methanol synthesis from syngas. The water-gas shift reaction over Cu/ZnO-based catalysts was also studied. The activity of Cu/ZnO/ZrO₂/Al₂O₃ catalyst for the water-gas shift reaction at 523 K was less affected by the pre-treatments such as calcination and treatment in H₂ at high temperatures than that of the Cu/ZnO/Al₂O₃ catalyst. Accordingly, the Cu/ZnO/ZrO₂/Al₂O₃ catalyst was considered to be more suitable for practical use for the water-gas shift reaction. The Cu/ZnO/ZrO₂/Al₂O₃ catalyst was also highly active for the water-gas shift reaction at 673 K. Furthermore, a two-stage reaction system composed of the first reaction zone for the water-gas shift reaction at 673 K and the second reaction zone for the reaction at 523 K was found to be more efficient than a one-stage reaction system. The addition of a small amount of colloidal silica to a Cu/ZnO-based catalyst greatly improved its long-term stability in the water-gas shift reaction in a similar manner as in methanol synthesis from CO₂ and H₂.     

浆态床二甲醚合成中V2O5、Sm2O3对脱水组分γ-Al2O3的修饰作用

采用等容浸渍法制备改性脱水催化剂,通过H2-TPR、Pyridine-IR、还原态NH3-TPD、XRD等表征手段,以及目标反应浆态床CO+H2合成二甲醚,研究了催化剂的还原性能以及酸中心分布与反应性能之间的关系。H2-TPR结果表明,在脱水催化剂γ-Al2O3、V2O5/γ-Al2O3和Sm2O3/γ-Al2O3上不出现还原峰,V2O5、Sm2O3的加入改善了复合催化剂中Cu的还原性能,促进了甲醇催化剂的还原。Pyridine-IR表明,V2O5和Sm2O3的加入对L酸、B酸的量影响不大。还原态NH3-TPD说明V2O5和Sm2O3的加入改变了酸中心的分布,增加了弱酸中心的比率。XRD结果发现,V2O5和Sm2O3均匀分散在γ-Al2O3上,没有新的物种生成。二甲醚合成目标反应的结果表明,改性后催化剂的反应活性增强,合成反应中CO转化率、二甲醚的选择性都得到提高。V2O5和Sm2O3的添加增加了弱酸中心数量,促进了脱水活性,从而提高了复合催化剂合成二甲醚的活性和选择性。     

Adaptation of Cu/ZnO/Al_2O_3 to Temperature Change in Methanol Synthesis from CO_2 Hydrogenation

The induction behavior in CO2 hydrogenation was studied by varying the reaction temperature to investigate the adaptation of the Cu/ZnO/Al2O3 catalyst to the temperature change. The results indicated that a used catalyst had a tendency to keep the last running state in new reaction conditions for MeOH formation, and that this tendency was related to the difference in Cu/Cun+ ratio caused by CO2 and CO produced at different reaction temperatures. However, the reverse water-gas shift reaction (RWGS) induced at four temperatures was completely different from that of methanol synthesis. It implied that the two so-called competitive reactions in CO2+H2, RWGS and methanol synthesis, have different active centers.     

Studies toward the synthesis of oximidines I and II

The synthesis of compound 1, a precursor for the synthesis of the oximidine II core structure 2, is described. An undesired C8-C9 isomerization occurred during the intramolecular Castro-Stephens reaction leading to macrocyle 3. The thermodynamic driving force for this unexpected isomerization was established by DFT and MP2 calculations. [reaction: see text]     

Concise preparation of 2,2-difluorohomopropargyl carbonyl derivatives. Application to the synthesis of 4,4-difluoroisoquinolinone congeners

A scalable synthesis of 2,2-difluorohomopropargyl esters was achieved using a magnesium-promoted Barbier reaction of substituted difluoropropargyl bromides with alkyl chloroformates. These 2,2-difluorohomopropargyl esters were effective precursors in the synthesis of homopropargylic amides-by aminolysis using AlMe3, as well as of ketones-through the reaction of the corresponding Weinreb amides with Grignard reagents. Ring closing metathesis using difluorinated 1,7-enyne carbonyl compounds furnished six-membered diene products, which were used as susbstrates in a Diels-Alder reaction to afford 4,4-difluoroisoquinolin-3-ones. The [2 + 2 + 2] cycloaddition of alkynes with fluorinated 1,7-diyne amides gave 4,4-difluoro-1,4-dihydro-3(2H)-isoquinolinone derivatives regioselectively.     

Adaptation of Cu/ZnO/Al2O3 to Temperature Change in Methanol Synthesis from CO2 Hydrogenation

The induction behavior in CO2 hydrogenation was studied by varying the reaction temperatureto investigate the adaptation of the Cu/ZnO/Al2O3 catalyst to the temperature change. The resultsindicated that a used catalyst had a tendency to keep the last running state in new reaction conditionsfor MeOH formation, and that this tendency was related to the difference in Cu/Cun+ ratio caused byCO2 and CO produced at different reaction temperatures. However, the reverse water-gas shift reaction(RWGS) induced at four temperatures was completely different from that of methanol synthesis. It impliedthat the two so-called competitive reactions in CO2+H2, RWGS and methanol synthesis, have differentactive centers.     

Synthesis of a muscarinic receptor antagonist via a diastereoselective Michael reaction, selective deoxyfluorination and aromatic metal-halogen exchange reaction

An efficient synthesis of a structurally unique, novel M(3) antagonist 1 is described. Compound 1 is conveniently disconnected retrosynthetically at the amide bond to reveal the acid portion 2 and the amine fragment 3. The synthesis of key intermediate 2 is highlighted by a ZnCl(2)-MAEP complex 19 catalyzed diastereoselective Michael reaction of dioxolane 7 with 2-cyclopenten-1-one (5) to establish the contiguous quaternary-tertiary chiral centers and a subsequent geminal difluorination of ketone 17 using Deoxofluor in the presence of catalytic BF(3).OEt(2). The synthesis of the amine moiety 3 is highlighted by the discovery of a novel n-Bu(3)MgLi magnesium-halogen exchange reaction for selective functionalization of 2,6-dibromopyridine. This new and practical metalation protocol obviated cryogenic conditions and upon quenching with DMF gave 6-bromo-2-formylpyridine (26) in excellent yield. Further transformations afforded the amine fragment 3 via reductive amination with 35, Pd-catalyzed aromatic amination, and deprotection. Finally, the highly convergent synthesis of 1 was accomplished by coupling of the two fragments. This synthesis has been used to prepare multi-kilogram quantities of the bulk drug.     

Mixed organofluorine-organosilicon chemistry. 13. One-pot synthesis of difluoroaldols from acylsilanes and trifluoromethyltrimethylsilane. application to the synthesis of a difluoro analogue of egomaketone

Difluoroaldol compounds 3 were synthesized in a one-pot procedure involving an acylsilane 1, trifluoromethyltrimethylsilane (TFMTMS), and an aldehyde. The key intermediate of this reaction is a difluoroenoxysilane 2. Ytterbium triflate proved to be a very efficient catalyst for promoting the aldol type reaction under very mild conditions. The potential of this reaction for the convergent synthesis of difluorinated compounds was illustrated by the synthesis of difluoroegomaketone 7d through dehydration of the corresponding aldol compound 3d.     

Direct spectroscopic evidence of the cross-coupling reaction between CH(2)(a) and CF(3)(a) on Ag(111)

The cross-coupling reaction between CH2 and CF3 on Ag(111) was studied with reflection absorption infrared spectroscopy (RAIRS) and temperature-programmed reaction spectroscopy (TPRS). Adsorbed CF3CH2(a) was, for the first time, spectroscopically identified as an intermediate in the reaction to form CF2CH2. It is formed by migratory methylene insertion into Ag-CF3. CF3CH2(a) undergoes beta-fluoride elimination to form CF2CH2. Our results provide direct new fundamental insight into Fischer-Tropsch synthesis.     

固相反应合成Ba1.0Co0.7Fe0.2Nb0.1O3-δ的动力学

依据新的固相反应模型, 采用非等温热重和差示扫描量热法研究了由BaCO3和Co3O4、Fe2O3、Nb2O5粉末固相反应合成Ba1.0Co0.7Fe0.2Nb0.1O3-δ的动力学. 考察了高速机械搅拌方式混料和球磨方式混料对合成动力学的影响. 结果表明, 反应过程分为两个阶段: 第一阶段为BaCO3和Co3O4、Fe2O3、Nb2O5之间的加成反应;第二阶段为加成反应生成的BaCoO3、BaFeO3和BaNbO3三相之间固溶生成均相的Ba1.0Co0.7Fe0.2Nb0.1O3-δ, 此过程中伴随有氧的脱出. 应用修正的模型对实验结果进行了拟合, 实验数据和理论模型符合良好. 高速机械搅拌样品加成反应阶段的活化能为376.76 kJ·mol-1, 仅为球磨样品加成反应阶段活化能494.76 kJ·mol-1的3/4. 高速机械搅拌工艺促进了离子的扩散, 有利于后续反应的进行, 是更为有效、节能、环保的混料方式.     

A formal total synthesis of roseophilin: cyclopentannelation approach to the macrocyclic core

[formula: see text] The formal total synthesis of the macrocyclic core of roseophilin 4 has been accomplished in 12 steps from 5-hexenal 8. The cyclopentannelation reaction was used to form the aliphatic five-membered ring of 3. Diene 2 was assembled by means of a Stetter reaction. Ring-closing metathesis of 2, reduction, and Knorr reaction of the 1,4-diketone 5 gave the ketopyrrole 3.     

Adaptation o Cu／ZnO／Al2O3 to Temperature Change in Methanol Synthesis from CO2 Hydrogenation

The induction behavior in CO2 hydrogenation was studied by varying the reaction temperature to investigate the adaptation of the Cu/ZnO/Al2O3 catalyst to the temperature change,The results indicated that a used catalyst had a tendency to keep the last running state in new reaction conditions for MeOH formation,and that this tendency was related to the difference in Cu/Cu^n ration caused by CO2 and CO produced at different reaction temperatures,However,the reverse water-gas shift reaction (BWGS) induced at four temperatures was completely different from that of methanol synthesis,It implied that the two so-called competitive reactions in CO2 H2,RWGS and methanol synthesis,have different, active centers.     

14C-labeled and large-scale synthesis of the angiotensin-(1-7)-receptor agonist AVE 0991 by cross-coupling reactions

The synthesis of (14)C-labeled AVE 0991 ((14)()C-1a) and large-scale synthesis of AVE 0991 (1a) are described. In the key step of the synthesis, the C-C coupling reaction of the imidazole (2) and thiophene (3) building blocks was studied under Suzuki and Stille reaction conditions, respectively. Suzuki reaction gave only moderate yields, whereas the best results were obtained under Stille reaction conditions with up to 64% yield.     

Total synthesis of (+)-cocaine via desymmetrization of a meso-dialdehyde

[reaction: see text] The total synthesis of (+)-cocaine is described. An extension of the recently reported proline catalyzed intramolecular enol-exo-aldol reaction to a meso-dialdehyde provided the tropane ring skeleton directly with good enantiomeric excess. The meso-dialdehyde was prepared using a 2-azaallyllithium [3 + 2] cycloaddition to generate a cis-2,5-disubstituted pyrrolidine. Overall, the synthesis proceeded in 6.5% yield and 86% ee over 14 linear steps starting from commercially available 3-benzyloxy-1-propanol.