538342-16-4Relevant articles and documents
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
Nakamura, Satoshi,Sugimoto, Hiromichi,Ohwada, Tomohiko
, p. 1724 - 1732 (2007/10/03)
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 α-carbon atom with respect to the nitro group facilitates deprotonation at the α-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 σp 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 α-proton with respect to the nitro group is influenced by the substituents on the benzene ring. Experimentally, we excluded the 6π 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.
Retro-Diels-Alder reaction of 4H-1,2-benzoxazines to generate o-quinone methides: Involvement of highly polarized transition states
Sugimoto, Hiromichi,Nakamura, Satoshi,Ohwada, Tomohiko
, p. 10088 - 10095 (2008/04/12)
(Chemical Equation Presented) Here, we describe mechanistic studies of the retro-Diels-Alder reaction of 4H-1,2-benzoxazines bearing various substituents on the benzene ring. 4H-1,2-Benzoxazines are very simple, but quite new, heterocyclic compounds that afford substituted o-quinone methides (o-QMs) through retro-Diels-Alder reaction under mild thermal conditions. The resultant o-QMs undergo Diels-Alder reaction in situ with dienophiles to give phenol and chroman derivatives. The mechanism of the generation of o-QMs has been little studied. Our experimental and density functional theory (DFT) studies have yielded the following results. (1) The generation of o-QMs, i.e., the retro-hetero-Diels-Alder reaction of 4H-1,2-benzoxazines, is rate determining, rather than the subsequent Diels-Alder reaction of the resultant o-QM with dienophiles. (2) The reaction rate is strongly influenced by the electronic features of substituents and the polarity of the solvent. The reaction proceeds faster in a polar solvent such as dimethyl sulfoxide, probably because of stabilization of the electronically polarized TS structure. (3) The reactions show characteristic positional effects of substitution on the benzene ring. While an electron-withdrawing group such as CF3 at C5, C6, or C7 positions decelerates the reaction, the same substituent at C8 accelerates the reaction, compared with the reaction of unsubstituted 4H-1,2-benzoxazine. In particular, substitution at C5 significantly decelerates the reaction as compared with the unsubstituted case. This is due to the difference in the inductive effect of CF3 at the different positions. Similar positional effects occur with a halogen (Cl) and a nitro group. All these data support the involvement of polarized TS structures, in which the O-N bond cleavage precedes the C-C bond cleavage.
