5-(R)BENZYLIDENE-2,2-DIMETHYL-1,3-DIOXANE-4,6-DIONES IN SYNTHESIS OF AROMATIC OXIMES, THIOSEMICARBAZONES AND HYDRAZONES

The behavior of some derivatives of Meldrum's acid, namely, 5-(R)benzylidene-2,2-dimethyl-1,3-dioxane-4,6-diones (a well-known synthetic platform) was studied with mono- and biazanucleophiles (hydrochloric hydroxylamine, thiosemicarbazide, hydrazine hydrate). The reaction of the reagents was carried out in acetic acid in a 1:1 molar ratio at 75 degrees C for 6-8 h, which resulted in aromatic oximes, thiosemicarbazones and hydrazones. The synthesis of (E)-4-chlorobenzaldoxime, (E)-N-(4-nitrobenzylidene) hydroxylammonium chloride, (E)-2-(4-chloro)-and (E)-2-(4-nitrobenzylidene) hydrazine-l-carbothioamides is probably accompanied by the formation of the Michael beta-adduct with the subsequent elimination of Meldrum's acid. The interaction of nitrobenzylidene dioxanedione with hydrazine hydrate occurs to form a mixture of (E)-N-(4-nitrobenzylidene) acetohydrazide, (E)-(4-nitrobenzylidene) hydrazine and acetate of the latter in a ratio of 17:3:1, found from the integral signal intensity in the 111 NMR spectrum (the ratio of similar products was 6:2:1 for chlorobenzylidene dioxanedione). It has been shown that during the reaction the studied substrates are attacked by two hydrazine molecules at the arylidene fragment and the carboxyl group of the opened dioxane cycle of Meldrum's acid. Further, the intermediates are recondensed to form hydrazones and acetylhydrazides. The latters interact with the aromatic aldehydes arising under these conditions as a result of the Knoevenagel retroreaction of the substrates, with the formation of major products, mixtures of (E)-N-(4-chloro)- or (E)-N-(4-nitrobenzylidene) acetohydrazides. Thus, under the selected conditions, in contrast to the common mechanism presented in the periodicals, no formation of N-heterocyclic systems is observed. The structure of the compounds obtained was confirmed on the basis of H-1, C-13 NMR spectroscopy data, as well as elemental analysis. Methods of two-dimensional heteronuclear correlation spectroscopy (HSQC) were also used for more reliable identification of the signals of the products (the components of mixtures).

Automated summary

The behavior of some derivatives of Meldrum's acid with mono- and biazanucleophiles was studied, resulting in the synthesis of aromatic oximes, thiosemicarbazones and hydrazones. The structures of the compounds obtained were confirmed based on H-1, C-13 NMR spectroscopy data and elemental analysis. Contrary to the common mechanism presented in the periodicals, no formation of N-heterocyclic systems was observed under the selected conditions.