The (2H)-1,4-benzoxazin-3(4H)-one ring system is present in a number of biologically active natural products including the phytoalexins of grasses, which are formed in vitro by the hydroxylation of (2H)-1,4-benzoxazin-3(4H)-one. 1 In connection with the preparation of potential anti-fungal agents modelled on these compounds, we had occasion to examine the aromatic substitution of some (2H)-1,4-benzoxazin-3(4H)ones. 2 Prior work on the aromatic substitution of (2H)-1,4benzoxazin-3(4H)-one has shown that monobromination gave firstly the 6-bromo and then the 6,7-dibromo derivative. 3 In contrast to this, nitration has been reported 4,5 to give the 6-nitro and then the 6,8-dinitro compound. Nitration of the 6-chloro compound gave the 6-chloro-7-nitro-1,4-(2H)-benzoxazin-3(4H)-one. 6 We have confirmed the orientation of these substitutions by nuclear Overhauser effect (nOe) enhancements based on irradiation of the N-H signal. This led to the identification of the H-5 signal. We have then extended the study of the aromatic substitution under different conditions in the context of preparing polysubstituted derivatives.Bromination of (2H)-1,4-benzoxazin-3(4H)-one 7 (4, Scheme 1) with bromine in glacial acetic acid gave firstly the 6-bromo 3 and then the 6,7-dibromo compound 1 whilst bromine in chloroform gave mainly the 7-bromo derivative 6. Bromination of the 6-chloro-and 6-methyl-(2H)-1,4-benzoxazin-3(4H)-ones and (2H)-1,4-benzothiazin-3(4H)-ones gave the 7-bromo compounds. Nitration of (2H)-1,4-benzoxazin-3(4H)-one 4 with a sulfuric acid:nitric acid mixture gave the 6-nitro 5 and then the 6,8-dinitro compound 2 whilst nitrosation : nitration with sodium nitrite:fuming nitric acid gave mainly the 7-nitro compound 7. 6-Chloro-(2H)-1,4-benzoxazin-3(4H)-one gave the 7-nitro compound.The orientation of bromination of these (2H)-benzoxazin-3 (4H)-ones parallels that of the substitution reactions of N-acetyl-o-anisidine including dibromination which gives 4, 5-dibromo-2-methoxyacetanilide. 9 However, dinitration gives 4,5-dinitro-2-methoxyacetanilide 10 and the 4,6-dinitro compound is only obtained on further nitration of 4-nitro-2methoxy-N-toluene-p-sulfonylaniline. 11 Techniques used: NMR spectroscopy, nOe enhancements References: 11
Oxazine derivativesOxazine derivatives R 0595The Bromination and Nitration of Some (2H)-1,4-Benzoxazin-3(4H)-ones. -The orientation of bromination and nitration respectively is studied for different reaction conditions. -(HANSON*, J. R.; RICHARDS, L.; ROZAS, P.; J. Chem. Res., Synop. 2003, 11, 681; Dep. Chem., Univ. Sussex, Brighton BN1 9QJ, UK; Eng.) -H. Haber 25-171
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