新型高效酯氢化还原催化剂的设计与筛选

Reduction of carboxylic acid esters to alcohols is one of the fundamental reaction in organic chemistry and widely applied in fine chemical industry such as pharmaceuticals, agrochemicals, food additive, eletronic products etc.Up to now, the reduction of esters still have relied mostly on using of the stoichiometric metal hydride reagents, such as LiAlH4, NaBH4, and their derivatives.It has produced a great pollution, due to a great amount of waste generated by this process.At the same time, the product cost is expensive.It is an ideal "green" method for the reduction of esters with catalytic hydrogenation with an efficent catalysts instead of currently reduction method. Although a great progress in the homogeneous catalytic reduction of esters to alcohols in recently years, the main issue of the low efficient activity,narrow substrate scope and easily racemization in hydrogenation of chiral compounds in catalytic process still need to be solved.So in this project, we shall design and synthsize the new Ru (P^N ligand ) pincer complexs and using as hydrogenation catalysts.The structure of complexs will be deterimined by the modern spectroscopic methods NMR, X-ray single crystal diffractometer.The catalysts will be applied in catalytic hydrogenation of aromatic, aliphatic and hetercyclic carboxylic acid esters and α-,β-substituted chiral carboxylic acid esters. The reaction process is tracked by GC-MS or HPLC－MS. We desire to obtain the new reduction method of esters by hydrogenation. The relationship between the activity of hydrogenation esters with the structure of catalysts could be revealed.The mild high-efficiency and high selective catalysts could be screened through optimization of the struture of catalyst.It will lay a foundation for designing more efficient catalyst of hydrogenation esters which is suitable for industry.

有机酸酯还原成醇是有机化学的基本反应之一，在医药、农药、食品添加剂、电子产品等精细化工领域中广泛应用，目前常用大量的金属硼氢化物如NaBH4和LiAlH4将酯还原成醇，其生产成本较高，同时会产生大量废弃物，环境污染大。采用催化氢化还原替代现有的还原方法，是一个理想、绿色的解决方案。但由于酯氢化反应活性低，其氢化还原问题一直未能有效解决。在我们及国内外同行前期工作的基础上，本课题提出设计、合成新型钌的氮膦配体配合物作为催化剂，采用NMR、X-单晶衍射等现代光谱手段对其结构进行表征，将其用于芳香酸、脂肪酸酯类，杂环羧酸酯以及手性的α、β-羟基、氨基酸酯的催化氢化还原中，采用GC-MS、HPLC-MS等手段对反应过程进行跟踪。建立新的酯催化氢化还原方法，揭示酯氢化还原活性与催化剂结构之间的关系，通过优化催化剂结构，筛选出高效、温和、选择性高的催化剂，为设计适合工业化的酯氢化还原催化剂奠定基础。

针对目前精细化工行业中酯用金属硼氢化物和LiAlH4还原成醇环境污染大、成本高及安全性差的问题，提出了设计新型酯氢化还原催化剂，建立绿色、条件温和的酯氢化还原新方法；从设计、合成的大量络合物中筛选出5种PNN型金属钌的络合物，具有良好的催化性能。其中一种络合物实现了高效催化氢化19种不同的酯还原成醇，S/C=2000-100000，TON可达50000；此外还拓展到酰胺氢化还原成醇和胺，在0.1-1%mol.PNN-Ru(II)络合物催化下，在无碱存在，120℃条件下，35种酰胺氢化还原收率在60-99%。解决了目前酯、酰胺还原需用金属硼氢化物还原污染大、危险性高和成本高的问题，具有良好的工业化前景。同时还拓展了这些催化剂的新应用，仅用底物0.025%摩尔PNN型Ru络合物催化剂，实现26种γ-氨基醇与二级醇脱氢偶合成吡啶或喹啉的衍生物，收率最高可达92%。与国内外现有的此类催化剂相比提高近10-100倍，是目前此类催化剂活性最高的催化剂。该催化合成杂环化合物的新方法已经用到烯烃聚合的催化剂的合成上并取得良好的结果。另外利用底物0.025%mol新的PNN型Ru（II）配合物，实现了23种二级醇的直接脱氢成酮的反应，最高收率在90%以上，醇直接脱氢成酮，避免了使用氧化剂造成的环境污染，是一种非常有前景的绿色合成工艺。最后还发现了一种新型对空气稳定的亚胺型金属钌的络合物，可以在不对溶剂处理条件下，实现高效的氢转移反应，以0.1mol%的络合物为催化剂，以异丙醇为氢源和溶剂，在叔丁醇钾为助催化剂的作用下，实现了24种不同的酮还原成醇的反应，收率在60-99%。解决了氢转移反应必须要无水无氧操作，工业化生产难度大的问题。同时本课题还对催化氢化酯、酰胺，二级醇无受体脱氢，及γ-氨基醇与二级醇无受体脱氢偶联成杂环化合物的反应机理进行了深入研究，为设计更高效的酯，酰胺氢化催化剂，无受体脱氢及脱氢偶联催化剂奠定了基础。