Synthesis and relative stability of 3,5-diacyl-4,5-dihydro-1H-pyrazoles prepared by dipolar cycloaddition of enones and α-diazoketones
Synthesis and relative stability of 3,5-diacyl-4,5-dihydro-1H-pyrazoles prepared by dipolar cycloaddition of enones and α-diazoketones
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DOI：
10.1021/jo048741w
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发表时间：
2004-12-24
影响因子：
3.6
通讯作者：
Ess, D
中科院分区：
文献类型：
--
作者：
Jung, ME;Min, SJ;Ess, D
描述了一种不寻常的反应过程，该过程通过断裂重组机制产生了意想不到的杂环系统。因此，用甲磺酰叠氮化物处理三酮3-乙酰基-2,6-庚二酮1，除了得到预期的α-重氮酮3a之外，还得到二氢吡唑3c及其氧化产物吡唑3d。我们提出最初形成的α-重氮酮3a断裂成简单的α-重氮甲基酮和甲基乙烯基酮，然后进行分子间[2,3]-偶极环加成。对三氟甲基三酮2进行类似处理，再次得到吡唑4c。进行了进一步的实验，为我们的机械假设提供证据。因此，α-重氮苯乙酮 5 和 MVK 在温和条件下进行 [2,3]-偶极环加成，得到两种区域异构体二氢吡唑 6a 和 6b。有趣的是，它们以 2:1 的比例形成，这表明 6a 比 6b 更稳定。利用B3LYP密度泛函方法和6-31G*基组对6a和6b的结构进行优化，预计异构体6a比异构体6b稳定1.5 kcal/mol。这种能量差异可以通过乙酰基比苯甲酰基与腙结合的能力更大来合理化。这种共轭的差异反映在关键键长的差异上。因此我们发现了一种新的碎裂-环加成过程。我们还提供了二氢吡唑形成机制的证据，并进行了计算来支持这些发现。
An unusual reaction process that produced unexpected heterocyclic systems by a fragmentation-recombination mechanism is described. Thus treatment of the triketone, 3-acetyl-2,6-heptanedione, 1, with methanesulfonyl azide gave, in addition to the expected alpha-diazo ketone 3a, the dihydropyrazole 3c and its oxidation product, the pyrazole 3d. We propose that the initially formed alpha-diazo ketone 3a fragments into the simple alpha-diazomethyl ketone and methyl vinyl ketone which then undergo an intermolecular [2,3]-dipolar cycloaddition. Analogous treatment of the trifluoromethyl trione 2 again afforded a pyrazole 4c. Further experiments were carried out to lend evidence to our mechanistic hypothesis. Thus alpha-diazoacetophenone 5 and MVK underwent a [2,3]-dipolar cycloaddition under mild conditions to give the two regioisomeric dihydropyrazoles 6a and 6b. Interestingly these were formed in a 2:1 ratio, which suggested that 6a was more stable than 6b. The structures of 6a and 6b were optimized by using the B3LYP density functional method and the 6-31G* basis set and isomer 6a was predicted to be 1.5 kcal/mol more stable than isomer 6b. This energy difference could be rationalized by the greater capacity of the acetyl group than the benzoyl group to conjugate with the hydrazone. This difference in conjugation is reflected by key bond length differences. Thus we have discovered a novel fragmentation-cycloaddition process. We have also presented evidence for the mechanism of the formation of the dihydropyrazoles and carried out calculations to support these findings.