【摘要】：α,β-不飽和酮不僅自身具有一定的藥理作用,而且是一種廣泛應(yīng)用于醫(yī)藥農(nóng)藥制造及香料生產(chǎn)等工業(yè)過程的合成中間體。在合成許多藥物分子時(shí),為實(shí)現(xiàn)羰基的1,3-遷移,首先需要通過金屬試劑將α,β-不飽和酮轉(zhuǎn)換為相應(yīng)的烯醇化合物,然后通過氧化重排實(shí)現(xiàn)上述過程,目前常使用的氧化劑是有毒的金屬鉻試劑,本文以溫和的鄰苯二甲酰過氧化物為氧化劑,實(shí)現(xiàn)了對2-氧代烯丙醇類化合物氧化重排生成羰基遷移的α,β-不飽和酮反應(yīng)。經(jīng)過對反應(yīng)條件的篩選,將1當(dāng)量的2 -氧代烯丙醇類底物與1.5當(dāng)量的鄰苯二甲酰過氧化物,在80 ℃、N2氣氛、1,2-二氯乙烷(0.2 M)溶劑中反應(yīng)可以得到最佳收率。后嘗試擴(kuò)展反應(yīng)底物22個(gè),發(fā)現(xiàn)該反應(yīng)反應(yīng)條件較溫和,易操作,后處理簡單,且具有一定的官能團(tuán)容忍度,產(chǎn)率介于低到中等(10%-55%)。將是實(shí)驗(yàn)中副產(chǎn)物通過GC-MS、核磁共振進(jìn)行了相應(yīng)的表征分析,預(yù)測了可能存在的反應(yīng)機(jī)理為:底物的碳碳雙鍵的富電子進(jìn)攻�；^氧化物的過氧鍵,在羥基的β位生成碳正離子,后發(fā)生分子內(nèi)的1,2-H遷移,鄰苯二甲酸酐離去生成目標(biāo)產(chǎn)物。而副產(chǎn)物則可能由于逆羥醛縮合反應(yīng)引起。在對上述反應(yīng)的研究過程中,發(fā)現(xiàn)將過硫酸鉀作用于2-氧代烯丙醇類底物可以得到環(huán)內(nèi)雙鍵遷移的二烯化合物,經(jīng)過對反應(yīng)條件的篩選,將1當(dāng)量的2-氧代烯丙醇類底物與2當(dāng)量的過硫酸鉀,在80 ℃、N2氣氛、甲苯(0.1 M)溶劑中反應(yīng)作為最優(yōu)反應(yīng)條件,同時(shí)將16個(gè)底物用于該反應(yīng)的嘗試,發(fā)現(xiàn)反應(yīng)對含吸電子及給電子基團(tuán)的底物均表現(xiàn)良好的容忍性,且產(chǎn)率達(dá)到中等(10%-71%)的水平,但當(dāng)?shù)孜锟臻g位阻過大時(shí),則反應(yīng)無法發(fā)生。
[Abstract]:偽, 尾-unsaturated ketones not only have certain pharmacological effects, but also are widely used in pharmaceutical pesticide manufacturing and flavor production. In the synthesis of many drug molecules, in order to realize the 1, 3-migration of carbonyl groups, 偽, 尾-unsaturated ketones need to be converted into corresponding enol compounds by metal reagents, and then the above process is realized by oxidation rearrangement. At present, the oxidant commonly used is a toxic metal chromium reagent. In this paper, the oxidation rearrangement of 2-oxo-allyl alcohol compounds to form carbonyl transfer 偽, 尾-unsaturated ketone reaction was realized by using mild phthalyl peroxide as oxidant. After screening the reaction conditions, the optimum yield of 2-dichloroethane (0.2 M) was obtained by the reaction of 1 equivalent 2-oxoallyl alcohol substrate with 1.5 equivalent phthalyl peroxide in 80 鈩，

本文編號：2493295