羧酸酯还原制备醇的方法研究进展

羧酸酯还原成醇是有机化学中的一类重要反应,有着广泛的用途。在涉及此类还原反应的已有文献资料中,所使用的还原体系包括硼烷、氢化铝锂、二异丁基氢化铝、红铝、金属硼氢化物等,其中,这些体系的还原能力各不相同。本文简要介绍了以上不同还原体系的研究新进展,综述了不同还原体系用于酯还原反应的反应机理,并通过不同还原体系间的比较与实例列举,为酯的还原研究提供了一些新的思路和方法,如还原体系的投料配比、投料顺序及与不同添加剂的配伍均可影响反应结果,使部分反应的收率高达90%以上,并使酯还原成醇的反应以更温和的方式进行。指出反应选择性更好,适用范围更广,反应条件更温和的新试剂、新方法将不断涌现,这将会给羧酸酯还原的领域带来更新的发展。     

芳香羧酸甲酯的硼氢化钠还原

采用NaBH_4-THF-甲醇体系将芳香羧酸甲酯进行还原反应2～5h得到相应的醇,收率为70%～90%。实验证明,NaBH_4-THF-甲醇体系对于芳香羧酸甲酯的还原具有很好的选择性。     

4-甲基哌啶-2-羧酸乙酯盐酸盐的制备方法

正本发明涉及一种阿加曲班活性前体(2R,4R)-4-甲基哌啶-2-羧酸乙酯的中间体4-甲基哌啶-2-羧酸乙酯盐酸盐的制备方法:采用4-甲基吡啶-2-羧酸乙酯原料,用磷钼酸做催化剂氧化制得4-甲基吡啶-2-羧酸乙酯氮氧化物,再以甲醇或乙醇作溶剂,再经还原反应制得4-甲基哌啶-2-羧酸乙     

硼氢化钠在羧酸及其衍生物还原中的应用

硼氢化钠可以很容易的将醛和酮还原为相应的醇,甚至可以在水介质中等当量的反应,但在温和条件下却很难将羧酸、羧酸酯、酰胺、酰氯和氨基酸及其衍生物还原,往往需要大大过量而且长时间回流,即使这样收率也很低.通过加入甲醇、路易斯酸、碘等修饰剂可以显著的提高硼氢化钠的活性,从而将羧酸及其衍生物还原为相应的醇.介绍了硼氢化钠还原羧酸及其衍生物的机理,综述了硼氢化钠在羧酸、羧酸酯、酰胺、酰氯和氨基酸及其衍生物还原中的应用.     

海那替尼的合成工艺研究

由3,5-二甲基-1-氢-吡咯-2-羧酸叔丁酯-4-羧酸乙酯开始,经氧化、Wittig反应、氢化、水解、还原、甲磺酰化一系列反应后得到中间体6,再和(S)-1-氨基-3-吗啡啉-4-基-异丙醇进行亲核取代并经三甲基铝处理、甲酰化后得到中间体9,然后与5-氟-1,3-二氢-吲哚-2-酮反应最终得到海那替尼。     

溴化氢的冰乙酸溶液脱除苯磺酰基的研究

采用溴化氢的冰乙酸溶液与苯酚的混合物快速脱除N-苯磺酰基-4-乙酰基哌啶-4-羧酸乙酯中的苯磺酰基,避免了酸解法脱除苯磺酰基引起反应物的脱羧反应,得到了目标产物4-乙酰基哌啶-4-羧酸乙酯,产率和纯度高。通过对脱除反应液的分析,表明溴化氢的冰乙酸溶液与苯酚的混合物对苯磺酰基的脱除可能是一个氧化-还原过程,苯酚在其中起了消除溴并防止脱除产物溴化的作用。     

γ-内酯类化合物的合成

γ-内酯是一类重要的香料化合物。研究了以廉价易得的糠醛为原料制备γ-内酯的合成路线。以糠醛和1-溴丙烷、1-溴丁烷、1-溴己烷为起始原料,合成了γ-辛内酯、γ-壬内酯以及γ-十一内酯。糠醛首先与溴代烷的格氏试剂在乙醚中反应,生成1-(2-呋喃基)烷醇,反应产率在86%左右。1-(2-呋喃基)烷醇在质量分数为0.5%的氯化氢的乙醇溶液中回流,开环水解得4-氧代羧酸,反应产率在60%左右。4-氧代羧酸与氯化亚砜在甲醇中回流反应,得4-氧代羧酸甲酯,产率约93%。4-氧代羧酸甲酯用硼氢化钠在甲醇中室温搅拌2 h,还原并且同时关环得γ-内酯,产率约85%。     

4-[2''-(反式-4"-正丙基环己基)乙基]环己酮的合成

以反式-4-正丙基环己基甲酸和4-羰基环己基甲酸乙酯为原料,通过羧酸还原、溴代反应、羰基保护、酯还原、格氏反应、水解、醇脱水、加氢等8步反应合成了乙烷类液晶中间体4-[2’-(反式-4"-正丙基环己基)乙基]环己酮,熔点34.56℃。并用气相-质谱(GC-MS)、红外光谱(IR)、核磁共振氢谱(1H NMR)确认了结构。     

4-[2’-（反式-4”-正丙基环己基）乙基]环己酮的合成

以反式-4-正丙基环己基甲酸和4-羰基环己基甲酸乙酯为原料,通过羧酸还原、溴代反应、羰基保护、醑还原、格氏反应、水解、醇脱水、加氢等8步反应合成了乙烷类液晶中间体4-[2’-（反式-4”-正丙基环己基）乙基]环己酮,熔点34.56℃。并用气相-质谱（GC-MS）、红外光谱（IR）、核磁共振氢谱（^1H NMR）确认了结构。     

1-甲基-3-正丙基-4-氨基-5-吡唑羧酰胺的制备

1 甲基 3 正丙基 5 吡唑羧酸经硝酸 -浓硫酸硝化制得 1 甲基 3 正丙基 4 硝基 5 吡唑羧酸 ,收率 85 %;用氯化亚砜将其酰氯化制得 1 甲基 3 正丙基 4 硝基 5 吡唑羧酰氯 ,该吡唑羧酰氯与浓氨水反应制得 1 甲基 3 正丙基 4 硝基 5 吡唑羧酰胺 ,收率 90 %;硝基吡唑羧酰胺在乙醇中用氯化亚锡还原制得 1 甲基 3 正丙基 4 氨基 5 吡唑羧酰胺 ,收率 84%。研究了反应的较佳合成工艺条件 ,产品经TLC、IR及MS谱进行了结构表征。     

硼氢化钠体系作还原剂对羰基的还原

羧酸的还原是有机化学中的重要反应。羰基在一般条件下不易被化学还原剂还原。硼氢化钠作为还原剂选择性好,性质温和,且价格低廉;它在工业上得到广泛的应用。本文拟对硼氢化钠作还原剂对羰基的还原作一介绍。     

Selective electroreduction of pyruvic acid on lead electrode in acid medium

This work reports the electrochemical reduction of pyruvic acid, which contains a carbonyl group more reducible than its carboxylic entity. The electrode potential and the concentration of the starting substrate seemed to be the factors that control the electrochemical production of the competitive reaction products. In fact, lactic acid was mainly obtained on a lead electrode in sulfuric acid for low concentrations of pyruvic acid while 2,3-dimethyl tartaric acid was selectively formed by electrohydrodimerization of a high amount of pyruvic acid. During the cathodic reduction of pyruvic acid in sulfuric acid solution, the effects of electrode potential and pyruvic acid concentration on the selectivity towards the formation of lactic acid were systematically studied.     

Mechanism of crosslinking of papers with polyfunctional carboxylic acids

Brief thermal curing of papers treated with an aqueous solution of polyfunctional carboxylic acids and NaH₂PO₄ imparts substantial wet strength to the papers. The effectiveness of such carboxylic acids increases with their functionality in the order 1,2,3,4-butanetetracarboxylic acid (BTCA) > tricarballylic acid (TCA) ? succinic acid. The two main stages of the curing reaction of papers, i.e., pendant attachment of the polyfunctional carboxylic acids via esterification with cellulosic hydroxyl groups, and its further reaction with another cellulose hydroxyl group producing crosslinks of the cellulose fibers were analyzed separately using a combination of acid-base and conductometric titrations. The extent of reaction of the polyfunctional carboxylic acids with paper was followed by pH titration, which shows the total decrease in acid functions as the curing progresses and is directly related to the total consumption of carboxylic acids groups by ester attachment and ester crosslinking steps. The conductometric titration, on the other hand, measures the increase in carboxylic acids bound to cellulose units of the paper as a direct result of previous esterification steps. Our studies reveal that the reaction of BTCA with papers is essentially quantitative after 15 min of curing. The amount of once-reacted BTCA increases in the initial phases of the curing reaction and then decreases as more and more carboxylic acid units are converted into crosslinking sites, while the amount of crosslinked BTCA increases throughout the curing reaction. The reaction profile of papers with TCA differs from that of BTCA in that the curing reaction is initially dominated by the formation of ester appendages; crosslinking becomes the main reaction only after extended curing times. We attribute this difference to the ability of BTCA to form an highly reactive difunctional crosslinking reagent at the outset of the curing reaction, while TCA is initially monofunctional in its reaction with cellulosic hydroxyl groups (formation of a monoanhydride). The relationship between the wet tensile strength of the treated papers and their degree of crosslinking is also discussed. © 1995 John Wiley & Sons, Inc.     

Kinetic and thermodynamic measurements for the facile property prediction of diels–alder‐conjugated material behavior

The Diels–Alder (DA) reaction between maleimide and furan moieties possessing various substitutions was performed as a means for developing predictive capabilities for temperature and conversion‐dependent material properties in networks comprised of DA moieties. Using HNMR spectroscopy, the reactions of maleimide‐ and furan‐containing molecules further functionalized with carboxylic acids were monitored to ascertain the impact that substitutional changes had on the thermodynamic and kinetic behavior of the DA reaction. The reaction rate and equilibrium conversion of the furan and maleimide increased when the carboxylic acid functional group directly connected to the furan ring was moved from the two to the three position. When an aliphatic two‐carbon spacer was used, such that the π‐electrons of the carboxylic acid and furan were no longer conjugated, the reaction rate increased further. We also report the reactivity effect on the distance between the carboxylic acid functional group and the maleimide, which yielded little impact on the reaction rate but exhibited increased equilibrium conversion with increasing distance. Additionally, the impact on the kinetic and thermodynamic properties of coupling the carboxylic acid to another molecule, tert‐butyl glycine, was also determined. When the carboxylic acid was coupled to an amine, the DA reaction between the furan and maleimide was generally found to have similar kinetic and thermodynamic behavior as compared to their uncoupled, carboxylic acid equivalents. Thus, the characterized and tabulated kinetic and thermodynamic data presented herein enables the prediction of a broad set of temperature‐dependent chemical and material properties. Finally, we discuss practical limitations and nuances of the DA reaction, such as the potential for the maleimide to ring‐open in aqueous media via hydrolysis. © 2012 American Institute of Chemical Engineers AIChE J, 2012     

Synthesis of thermo- and pH-responsive polysilsesquioxane with carboxylic acid group

The thermoresponsive polysilsesquioxanes containing N-(methoxyethyl)methylamide structures with carboxylic acid groups were newly prepared. In the syntheses of the polysilsesquioxanes, the silane coupling reagent, obtained from the reaction of (3-isocyanatopropyl)trimethoxysilane and (2-methoxyethyl)methylamine, was used for the co-condensation with (3-mercaptopropyl)trimethoxysilane to give the polysilsesquioxane with mercapto group (MMEPSQ). MMEPSQ was employed as the intermediary compound to introduce carboxylic acid group through thiol-ene reaction. The polysilsesquioxane, which was prepared from the reaction of MMEPSQ and methacrylic acid showed the expected amphiphilic and thermoresponsive properties in an aqueous solution with addition of sodium hydroxide. The lower critical solution temperature (LCST) owing to hydrophobic aggregation increased with pH value of the aqueous solution. Furthermoe, the use of MMEPSQ for the reactions with maleic anhydride and successive ring-opening reaction by the amines, which contained pyridine or 15-crown-5-ether ring, enabled the formations of multi-functionalized polysilsesquioxanes. In the case of the polysilsesquioxane containing carboxylic acid groups and pyridine rings, the pyridinium salt structure was favorable to keep an enough solubility in water and the reversible thermoresponsive behavior. The polysilsesquioxane containing the crown ether and carboxylic acid groups, the selective ion recognition property to alkali metal ion was observed.     

Optimisation of the synthesis of a water-soluble sulfur black dye

A water-soluble sulfur black dye containing carboxylic acid groups was prepared by reducing C.I. Sulfur Black 1 to its leuco form followed by reaction with chloroacetic acid. In conducting this reaction, variables studied included the order of adding reactants, the amount of Na₂S and chloroacetic acid employed, and the time and temperature of the reaction. It was found that the carboxylic acid group content and reaction yield were maximized by controlling the amount of Na₂S and chloroacetic acid employed, and by conducting the reaction for 2 h at 60 °C.     

糖醛酸合成方法的研究进展

目前糖醛酸的合成主要是以单糖为原料氧化而得。分别就糖醛酸的几种常用合成方法进行了介绍,即直接将羟甲基氧化成羧基的一步法和先将羟甲基氧化成甲酰基、再氧化成羧基的两步法。并分别讨论了几种方法的优缺点、催化剂的选择及其适用的反应条件。