Formation of 4H-1,2-benzoxazines by intramolecular cyclization of nitroalkanes.: Scope of aromatic oxygen-functionalization reaction involving a nitro oxygen atom and mechanistic insights
Formation of 4H-1,2-benzoxazines by intramolecular cyclization of nitroalkanes.: Scope of aromatic oxygen-functionalization reaction involving a nitro oxygen atom and mechanistic insights
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DOI：
10.1021/ja067682w
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发表时间：
2007-02-14
影响因子：
15
通讯作者：
Ohwada, Tomohiko
中科院分区：
文献类型：
--
作者：
Nakamura, Satoshi;Sugimoto, Hiromichi;Ohwada, Tomohiko
本文研究了3-芳基-2-硝基丙酸甲酯在强Bronsted酸催化下的分子内环化反应合成4H-1，2-苯并恶嗪的范围和机理。这个反应可以看作是芳环的氧官能化，其中氧原子来自分子中的硝基，苯环上存在吸电子基团有利于该反应。反应速率受反应介质酸度的影响较大，α-碳原子上的甲酯基团相对于硝基有利于α-位的去质子化，从而原位生成ACI-硝基物种。在三氟甲磺酸(TFSA)/三氟乙酸(TFA)介质中，取代基对苯的吸电子能力(用取代基的Hammett‘s sigma(P)值表示)与导致产物的起始底物消失率之间存在一定的相关性。这是因为α-质子相对于硝基的酸性受苯环上取代基的影响。在实验上，我们排除了涉及质子化ACI-硝基物种的苄基质子去质子化的6pi电环反应机理。含有O-质子化酯基的单阳离子ACI-硝基物种和O-质子化的ACI-硝基物种的替代环化反应机理在能量上是非常不利的。二质子化或原溶解物种可以显著降低环化反应的活化能，这与观察到的环化反应的酸性相关性质是一致的。
In this paper, we deal with the scope and mechanism of the strong Bronsted acid-catalyzed intramolecular cyclization reaction of methyl 3-aryl-2-nitropropionates to give 4H-1,2-benzoxazines. This reaction can be regarded as an oxygen functionalization of the aromatic ring wherein the oxygen atom is derived from the nitro group in the molecule, and it is favored by the presence of electron-withdrawing groups on the benzene ring. The reaction rate is strongly influenced by the acidity of the reaction medium, and the methyl ester group on the alpha-carbon atom with respect to the nitro group facilitates deprotonation at the alpha-position to give aci-nitro species in situ. Some correlation was found between the electron-withdrawing ability of the substituents on benzene, represented in terms of Hammett's sigma(p) value of the substituents, and the rate of disappearance of the starting substrate leading to the product in trifluoromethanesulfonic acid (TFSA)/trifluoroacetic acid (TFA) medium. This would be because the acidity of the alpha-proton with respect to the nitro group is influenced by the substituents on the benzene ring. Experimentally, we excluded the 6 pi electrocyclization mechanism involving deprotonation of the benzyl proton of the protonated aci-nitro species. Alternative cyclization mechanisms involving equilibrating monocationic aci-nitro species bearing O-protonated ester carbonyl group and O-protonated aci-nitro species were calculated to be highly energetically unfavorable. Diprotonated or protosolvative species can reduce the activation energy significantly, and this is consistent with the observed acidity-dependent nature of the cyclization.