【作者】 窦国兰；

【导师】 史达清；

【作者基本信息】 苏州大学 ， 有机化学， 2010， 博士

【摘要】 低价钛试剂是一种很重要的新型有机合成试剂。这种试剂被广泛应用于分子内和分子间的还原偶联等反应。本论文主要研究了低价钛试剂作用下的还原偶联反应,共分为两个部分：第一部分,低价钛试剂作用下杂螺烯类似物的合成；第二部分,低价钛试剂促进的杂环化合物的合成研究。第一部分,我们以邻羟基(或硝基)芳醛和二胺为起始原料,先生成双亚胺后,在低价钛试剂作用下与固体光气发生还原环化反应,一步构建三个环,定向构筑含有氮、氧杂原子的杂螺烯骨架。我们通过改变醛组分的结构,得到[5]、[7]螺烯类似物,并用单晶X-射线衍射实验确定了产物的结构。另外,我们还发现当二胺组分为乙二胺及其取代物时,得到的是反式杂螺烯类似物,而当二胺组分为丙二胺时,得到的是顺式产物,因而我们可以通过调节二胺组分,从而得到立体构型不同的杂螺烯类似物。第二部分研究了低价钛试剂作用下杂环化合物的合成。第三章以1,3-二羰基化合物、醛、胺为原料,在低价钛试剂作用下发生三组分反应,一步合成了1,2,3,5-四取代吡咯以及氢化吲哚。该反应在15 min内完成,产率在75%-98%。对于非对称的1,3-二酮而言,只得到或主要得到一种产物,显示了较强的区域选择性,为多取代吡咯衍生物的合成提供了一种方便有效的方法。第四章研究了低价钛试剂作用下异硫氰酸酯与邻位硝基化合物的反应,异硫氰酸酯与邻硝基酰胺、邻硝基苯甲酸乙酯、2-邻硝基苯基咪唑、2-邻硝基苯基苯并咪唑发生还原环化反应生成喹唑啉酮以及喹唑啉衍生物,邻硝基苯甲酸乙酯与异氰酸酯在低价钛试剂作用下反应生成喹唑啉-2,4-二酮,对该反应,我们提出了可能的反应机理。第五章通过往低价钛试剂中添加三乙胺来调控反应体系的pH值,对反应产物进行选择性调控,从而实现在简便的条件下合成吲唑-3(2H)-酮的方法。该反应只需5-30 mmin即可完成,产率都在51%-82%之间。在实验时,我们发现当反应体系的pH值大约为9时,邻硝基苯甲酰胺可以在2-3 min之内以高产率反应生成邻氨基苯基腈,一步实现了两个官能团的转化。第六章,以邻硝基芳醛和芳胺为起始原料,经生成亚胺后在低价钛试剂作用下与固体光气反应,一步高产率得到双喹唑啉-2,2’-二酮。该反应在2h内完成,反应适应性比较广泛,为该类化合物的研究提供了一条方便、有效的合成方法。对合成的双喹唑啉-2,2’-二酮进行了抗癌活性的测定,发现其具有较好的抗癌活性。这类化合物的合成以及它的活性都是首次报道。第七章,以邻羟基芳醛和芳胺为起始原料,经生成亚胺后在低价钛试剂作用下与固体光气反应,一步高产率得到对称苯并[e][1,3]嗪-2,2’-二酮。该反应产率在73%-82%之间,反应时间短(2h)。同时我们发现邻羟基肟、邻羟基苯腙与固体光气在同样条件下都可以一步高产率地得到对称苯并[e][1,3]嗪-2,2’-二酮,而非对称的邻羟基双腙与固体光气在同样条件下可以高产率地得到非对称的苯并[e][1,3]嗪-2,2’-二酮。以上所研究的反应都具有原料易得,反应条件温和,操作简便,选择性好,产率较高等诸多优点。更多还原

【Abstract】 Low-valent titanium reagent is one of the new key organic synthesis reagents, which has been widely used in inter-and intra-molecular reductive coupling reactions. Our interest is to investigate reductive coupling reactions induced by low-valent titanium reagent. This dissertation consisted of two parts. The first one is focused on the synthesis of hetero-helicene-likes induced by low-valent titanium reagent. The second is the synthesis of heterocyclic compounds induced by low-valent titanium reagent.In part one,2-hydroxybenzaldehydes (or 2-nitrobenzaldehydes) and diamines were utilized as the starting materials, the formed diimines then undergo a reductive-cyclization process with triphosgene to give the nitogen, oxygen-containg helicene skeleton induced by low-valent titanium reagent. [5] and [7] helicene-like compounds have been synthesized by modifying the structure of aldehydes, and the structures of the products have been determined by the X-ray crystallographic analysis. In addition, when 1,2-diaminoethanes act as the substrates, the final products were found to be in the trans-isomer, while the propane-1,3-diamines gave the related products in syn-isomer, as a result, hetero-helicene-likes in different geometry could be synthesized by altering the diamine.The second one is focused on the synthesis of heterocyclic compounds induced by low-valent titanium reagent.In section three, a one-pot multicomponent reaction involving 1,3-dicarbonyl compounds, aldehydes and amines induced by low-valent titanium reagent, which gave new series of 1,2,3,5-tetrasubstituted pyrroles as well as hydroindoles have been disclosed. The reaction went smoothly and gave the target products in the yield of 75%-98% in 15 min. Moreover, for the unsymmetric 1,3-dicarbonyl compounds, only one kind of products were isolated, which provided an convenient and efficient protocol for the synthesis of polysubstituted pyrroles. This new method has the advantages of high regioselectivity.In the forth chapter, a facile reductive coupling reaction of nitro-compounds with isothiocyanates or isocyanates promoted by low-valent titanium reagent were studied: an access to 2-thioxoquinazolinone, quinazolin-2,4-dione, imidazo[1,2-c] quinazolin-5-amine and benzimidazo[1,2-c]quinazolin-5-amine derivatives.In the fifth chapter, a mild, efficient, one-pot protocol for the synthesis of indazole-3(2H)-ones via cyclization of nitro-aryl substrates through low-valent titanium reagent has been described. The method used triethylamine(TEA) to control pH. Particularly,2-aminobenzonitriles were synthesized by one step easily. The mechanistic course of the reaction suggests the involvement of an anion leading to an intramolecular cyclization via N-N bond formation.In the sixth chapter, the synthesis of a series of biquinazoline-2,2’-diones starting from o-nitrobenzaldehydes, anilines and triphosgene is presented. This general approach features a novel and easy way for access to the target products. The mechanistic course of the reaction suggests the involvement of reduction, coupling and cyclization by one-pot. These compounds were also investigated in vitro for anticancer activity, and some were found to have good anticancer activity.In the seventh chapter, symmetrical and unsymmetric bibenzo[e][1,3]oxazine-2,2’-diones were first synthesized in satisfactory to good yields via the reaction of triphosgene and various o-hydroxy Schiff base with the aid of low-valent titanium reagent. Possible mechanism as well as optimization and reaction scope studies are reported.The remarkable advantages of the above mentioned reactions are mild, neutral, simple operation, good yields and high selectivity.更多还原