特窗酸和特窗胺衍生物的合成方法研究

【作者】 潘玲；

【导师】 刘群；

【作者基本信息】 东北师范大学 ， 有机化学， 2004， 硕士

【摘要】 ?-羰基二硫缩烯酮类化合物1是一类重要的有机合成中间体（其?,?位有亲电性，可作为1，3亲电体；其?位有亲核性，可作为亲核体），广泛应用于芳环、杂环化合物的合成中。特窗酸、特窗胺及其衍生物均是生物活性很高的五员杂环化合物，具有重要的研究与实用价值。因此，将?-羰基二硫缩烯酮与特窗酸/胺的合成相关联是一值得探讨的研究内容。 本文首先从3-（1，1-二烷硫基）亚甲基5-吡啶甲基特窗酸4出发，初步研究了含有二硫缩烯酮结构单元的特窗酸的反应取向。 (1) 各种芳醛为亲电体与4a的反应，用以探讨反应的取向。 (2) 各种Grignard试剂为亲核试剂与4a的反应及反应的取向。 研究结果表明，（1）含(-二硫缩烯酮的特窗酸衍生物其?位的次甲基氢比?侧链中与吡啶基直接相连的亚甲基的氢活泼，反应过程中，电子效应占一定的主导地位，空间效应作用较小。（2）其?位羰基较酯羰基活泼，易受亲核试剂进攻，烷硫基对化合物反应活性有一定的调控作用。在研究化合物性质的同时我们合成了?-（1，1-二烷硫基）亚甲基-γ-（1-羟基，1-吡啶基）甲基-?’-吡啶甲基-特窗酸5、?-（1，1-二烷硫基）亚甲基-?-烷/芳基-?-吡啶甲基特窗酸7和少量的羧酸衍生物6。 随后，本文以2-（1，1-二烷硫基）亚甲基-3-羰基-5-吡啶/芳基-4-戊烯酸为底物，合成了一系列二-2-（1，1-二烷硫基）亚甲基-3-羰基-5-吡啶/芳基-4-戊烯基二酰胺8，并通过分子内吡啶乙基化反应实现了该类化合物的双环合，将多个羰基、吡啶基和二硫缩烯基完整的引入到特窗胺母体环中，通过碳链将两个特窗胺（吡咯烷酮）母体联接在一<WP=5>起，合成了化合物9，其特窗胺母体结构预示着他们较高的生物活性。本文所用的合成方法步骤少，方法简单，引入的活泼官能团多，这些官能团仍可进行各类反应，为合成特窗胺衍生物提供了良好前体。 本文还讨论了所涉及的各类反应的反应机理，影响反应的主要因素和反应条件的控制与优化，并结合文献展望了环上具有二硫缩烯酮结构单元的特窗酸、特窗胺的进一步应用。 本文合成了24个未见文献报道的新化合物，对所得化合物进行了IR、1H NMR等表征。更多还原

【Abstract】 ?-Oxo ketene dithioacetals 1 are a kind of versatile intermediates in organic synthesis. It can be widely used as 1,3-electrophile or nucleophilic reagent to form aromatic and heterocyclic compounds. Tetronic acid, tetronic amine and their derivatives are five-membered heterocyclic compounds along with bio- and pharmacological activities. The scientific and practical demands for such compounds are increasing. Therefore, the combination of ?-oxo ketene dithioacetals and the synthesis of tetronic acid/amine deserves investigation. In this thesis, tetronic acid 4 : 5-pyridinyl-methyl-3-(bis-alkylthio) methylene-furan-2,4-diones was selected for the studies of its reacting orientation firstly.Pyridine carboxaldehydes were selected as electrophiles and their reactions with 4 were investigated.Several Grignard reagents were prepared and used as nuleophilic reagents for the investigation of their reaction with 4 .We found that: (1) The ?-methine-H in tetronic acid is more active than the methylene-H connected with pyridine ring. The electronic effect seems more important than steric effect. (2) The ?-carbonyl carbon is more active than the ester carbonyl carbon and liable to the attack from nucleophilic reagents. Alkylthio groups of tetronic acids have effect,at least to some extent,on their reactivity.??-(Bis-alkylthio)methylene-?-(1-hydroxy-1-?pyridinyl)methylene-?’-pyrinyl methyl-tetronic acid 5,?-(bis-alkylthio) methylene-?-alkyl/aromatic -?-pyrinylmethyl-tetronic acid 7, and some carboxylic acid derivatives 6 were prepared. Next, a range of bis-2-(bis-alkylthio)-methylene-3-carbonyl-5- pyridin <WP=7>yl-4-petene-amide 8 were prepared.from2-(bis-alkylthio)methylene-3- carbonyl-5-pyridinyl/aromatic-4-pentenic acids. Then, tetronic acid derivatives 9 were synthesized via the intramolecular pyridinylethylation of 8. A number of carboxyls, pyridinyls and the unit of ketene dithioacetale were introduced integrally, two tetronic amine(pyrridiones) were connected by an alkyl chain. Due to their tetronic amine framework, these compounds have the potential of bio- and pharmacological activities. Associated with some synthetic advantages such as few preparation steps, mild conditions, simple procedure, these resulting compounds were highly functionized which lead them good candidates to serve as precursors for further synthetic transformations of tetronic amine. The mechanisms for the related reactions and the optimization of reaction conditions were discussed. Further investigation and potential application of these kinds of tetronic acids and amines were prospected in the light of our results and literatures as well. In this paper 24 new compounds were prepared and were characterized by IR and 1H NMR.更多还原