A New Synthetic Method of Alkyl Carbonocyanidate N-Oxides

Abstract

A thermal decomposition of dimethyl nitromalonate to bis(carbomethoxy)furoxan was observed at about 170 °C. In the presence of dipolarophiles, an intermediate, methyl carbonocyanidate N-oxide MeOCOC≡N→O, could be trapped as cycloadducts in good yields by the 1,3-dipolar cycloaddition. Treatment of dimethyl nitromalonate in mesitylene at the refluxing temperature resulted in a formation of methyl 2-(hydroxyimino)-2-(2,4,6-trimethylphenyl)acetate.

An anomalous hydration/dehydration sequence for the mild generation of a nitrile oxide

“…The above disadvantage was overcome by using excess dipolarophile, and the yield of 8a in this case was improved up to 72% (run 6). When THF was used as a co-solvent in the present reaction, 10 the yield of 8a was comparable to that mentioned in the previous sentence (run 7); however, acetonitrile was preferred because of the high solubility of 5a in this solvent. Other dipolarophiles 7b-d and 10a-l were subjected to cycloaddition under the optimized conditions used for 20 ethynylbenzene 7a ( Table 2, run 1).…”

“…The organic layer was concentrated, and the residue was subjected to column chromatography to 5 afford a mixture of 18 and 3d (eluted with hexane/CHCl 3 = 2/1, 23 mg, yield of 18; 18%, yield of 3d; 12%) and nitroenamine 18 (eluted with hexane/CHCl 3 = 1/1, 30 mg, 0.23 mmol, yield 46%). Although further purification of 3d was attempted by column chromatography again, impurity 10 could not be removed. The structural determination was performed by comparing spectral data with those of 3e, which was prepared from commercially available ethyl nitroacetate and ethyl isocyanate.…”

“…5 A method for the dehydration of ethyl nitroacetate to 1 has also been established; in this reaction, tolylene diisocyanate 45 (modified Mukaiyama method), 6 manganese(III) acetate, 7 acid chloride, 8 or trifluoroborane etherate 9 is employed as the generating agent. In addition, nitromalonate 10 and nitroacetoacetate 11 are known to be precursors of 1; however, these compounds have certain disadvantages: severe reaction 50 conditions must be employed when using nitromalonate, and nitroacetoacetate is highly unstable. Although De Sarlo and Machetti demonstrated an excellent protocol for preparation of functionalized isoxazol(in)es from nitroalkanes, active species were not functionalized nitrile oxides but activated 55 nitronates.…”

“…20c Since even anionic isoxazolone 4a is deprotonated by 5 pyrrolidine, the ring proton of N-methylisoxazolone 5a should be sufficiently acidic for easy deprotonation by water. 2,3-Dimethylnitroisoxazolone 5b, 25 which has no ring protons, remains intact under the same conditions to be recovered, although the steric effect of the additional methyl group in this 10 compound must be taken into consideration. On the basis of these observations, we propose a plausible mechanism for the generation of nitrile oxide 2d, as shown in Scheme 5.…”

“…On the other hand, when water attacks the carbonyl group of 15 (route d), 5 nitromalonic acid monoamide 17 is formed which readily undergoes dehydration and decarboxylation in a concerted manner to afford nitrile oxide 2d. Another possibility is that 15 may undergo prototropic rearrangement to form the lessstrained intermediate 16 (route e), the two electrophilic 10 carbons in which are attacked by water to give the nitromalonic acid derivative 17 (route f or g). In the present mechanism, nitroenamine 14 and nitromalonic acid derivative 17 are considered the key intermediates.…”