Nitrile oxide, Carbamoyl

The generation of a nitrile oxide bearing a carbamoyl group (i.e., 16) was effected by treating 4-nitro-3-isoxazoline-5-one (15) with a mixture of acetonitrile and water (Scheme 6.5). Although the mechanism of this reaction is not clear, the method allows for the formation of a functionalized nitrile oxide (16) and subsequent cycloaddition under mild conditions (91). 

As mentioned so far, methylnitroisoxazolone 10 serves as a precursor of carbamoylnitrile oxide 6 upon treatment with only water under mild conditions, in which any special reagents, conditions, and manipulations are not necessary. The nitrile oxide 6 reacts with alkynes 15, alkenes 17, nitriles 29, and 1,3-dicarbonyl compounds 34 to afford corresponding carbamoyl-substituted isoxazoles 16, isoxazolines 18, 1,2,4-oxadiazoles 28, and isoxazoles 33, respectively (Scheme 9.17). The electron-withdrawing carbamoyl group realizes the cycloaddition with electron-rich dipolarophiles, which is inverse electron-demand 1,3-dipolar cycloaddition. Furthermore, the carbamoyl group also plays a role of an activator of the dipolarophile. This mefliodology will be useful for the construction of a new library of functionalized compounds. 

Hydrolyses of carbamoylpyrazine A -oxides to carboxypyrazine IV-oxides have been described in Section 8A(2), deoxygenation and chlorination of carbamoylpyrazine A -oxides (A -unsubstituted carbamoyl compounds gave the nitrile) in Section V.IG, and deoxygenation of carbamoylpyrazine A -oxides (which also contained amino groups) in Section VIII.3C(4). In addition, 4-methyl-2-A -methyl-A -phenylcarbamoyl-3-oxo-3,4-dihydropyrazine 1-oxide refluxed with aqueous ethanolic sodium dithionite gave 4-methyl-2-Af-methyl-Af-phenylcarbamoyl-3-oxo-3,4-dihydropyrazine (1137), and 3,5-bis(methylamino)-3-A -methylcarbamoyl-pyrazine 1-oxide was deoxygenated by heating at 190-200° and 0.25 mm (462). 

Oxidation. Secondary a-amino nitriles afford a-imino nitriles upon reactin with IBX at room temperature. Tetrahydroisoquinoline is carbamoylated at C-1 and A -acylated at the same time on exposure to IBX and treatment with RCOOH and R NC." ... 

Oxidation catalyst. These compounds (1), as well as bis(2-carbamoyl)phenyl diselenides, are very effective catalysts for the oxidation of sulfides, dimethylhydrazones (to nitriles), and azines (to carbonyl comjwunds). 

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