利用丙二烯酮製備吡唑及異噁唑化合物 和 b-鹵素酮之新合成方法研究

Synthesis of Pyrazoles and Isoxazoles from Allenyl Ketones and A New Additional Reaction for Synthesis of b-Halo Ketones

王淑惠(Shu-Huei Wang)

指導教授 ： 李世元

淡江大學/理學院/化學學系博士班/博士(2005年)

https://doi.org/10.6846/TKU.2005.00677

摘要

第一部分：
吡唑(Pyrazole)和異噁唑(Isoxazole)化合物及其衍生物是許多天然物、藥物、抗生素、抗菌劑、殺蟲劑、除草劑、染料的基本架構，雖然有許多此類的雜環化合物的合成研究被報導過，但由於合成步驟繁瑣、方法及策略困難度高，常導致其合成在醫學及藥學的應用有許多限制與不便，因此我們提出一簡捷便利及具高幾何選擇性的合成方法來合成此類型化合物。我們利用丙二烯酮化合物與親核劑聯胺鹽類(H2N-NH2.2HCl)化合物於甲醇鈉(NaOMe)及二甲基醯胺(DMF)中進行加成和環化反應，可生成高產率的吡唑化合物；另一部分也是利用丙二烯酮化合物與親核劑羥胺鹽類(HO-NH2.HCl)化合物於碳酸銫(Cs2CO3)及二甲基亞碸(DMSO)中進行加成和環化反應，即生成單一幾何選擇產物的異噁唑化合物。我們亦證實反應的反應機構是親核劑(H2N-X, X = -NH2,-OH)的胺基先進行加成反應在丙二烯(Allene)b-位置的碳，而後胺基或氫氧基再與酮官能基進行加成反應，脫水後生成單一幾何選擇的五環吡唑及異噁唑化合物。
第二部分：
b-取代羰基化合物及其衍生物為許多生物活性分子和藥物之基本架構，通常b-取代羰基化合物合成的步驟常常過於繁瑣，而本實驗室研發合成烯丙基酮化合物和a,b-不飽和酮化合物的方法，可提供另一個溫和簡捷的合成方法來合成b-取代羰基化合物。本實驗室在合成b-取代羰基化合物方面已有豐碩的成果，目前已成功利用烯丙基酮化合物和a,b-不飽和酮化合物於路易士酸的促進下進行麥克加成反應，可合成b-甲氧基酮、b-胺基酮及b-醯胺基酮化合物。而本篇論文也提出利用a,b-不飽和酮化合物與三硼化氯或三硼化溴及乙二醇在二氯甲烷0℃下進行反應，成功的合成一系列不同取代基的b-鹵素酮化合物。因b-鹵素酮化合物及其衍生物為合成重要中間物，可進一步地擴充加以應用於許多重要的天然物和藥物的合成及不對稱合成反應上，大幅提升了此方法在有機合成上的應用價值。

關鍵字

吡唑 ； 異噁唑 ； 丙二烯酮 ； b-鹵素酮

並列摘要

Part I:
Pyrazole and Isoxazole are well-known as useful synthetic intermediates
and important structural units which are widely observed in natural
products and biological active molecules. Several methods for synthesis
of isoxazoles have been developed and reported and the cyclocondensation
reaction of b-diketone with hydroxylamine is one of the most common used
method. The limitation of this method is the unsymmetrical b-dicarbonyl
compounds can not be prepared regioselectively. The condensation reactions
of oxime dianions with esters provide a regioselective accesses to generate
b-keto oximes, which then undergo cyclodehydrations to afford isoxazoles.
We wish to report a new synthetic method which improves and permits a variety
of substituted pyrazoles and isoxazoles are easily prepared. Pyrazoles were
synthesized from a reaction mixture of hydrazine dihydrochloride, sodium
methylate and allenyl ketone in anhydrous N, N-dimethylformamide at room
temperature. Isoxazoles were synthesized from a reaction mixture of hydroxylamine
hydrochloride, cesium carbonate and allenyl ketone in anhydrous dimethyl
sulfoxide at room temperature.
Part II:
b-Halo carbonyl compounds are potentially biologically active molecules
and important synthetic intermediates in organic synthesis. Recently, our
laboratory reported a simple and an effective method for synthesis of
a,b-unsaturated ketone which is an useful synthetic precursor for
preparation of a,b-unsaturated ketone. A reaction mixture of a,b-unsaturated
ketone, boron trichloride and ethylene glycol in dichloromethane was stirred
at 0oC and b-chloro ketone was produced in high yield. The b-bromo ketone
was obtained as the major product when a reaction mixture of a,b-unsaturated
ketone , boron tribromide and ethylene glycol in dichloromethane was stirred
at 0oC after 0.5h.

並列關鍵字

Pyrazole ； Isoxazole ； Allenyl Ketone ； b-Halo Ketone

參考文獻

(2)Jones, R. G. J. Am. Chem. Soc. 1949, 71, 3994.

(3)Jones, R. G.; Mann, M. J. J. Am. Chem. Soc. 1953, 75, 4048.

(5)Buchanan, J. G.; Stobie, A.; Wightman, R. H J. Chem. Soc., Perkin Trans. 1 1981, 2374.

(11)Marques-Soares, C.; Dijoles, S.; Macherey, A.-C.; Wester, M. R.; Johnson, E. F.; Dansette, P. M.; Mansuy, D. Biochemistry 2003, 42, 6363.

(13)Dorn, H. Chem. Ber. 1965, 98, 3368.