Synthesis of Bis‐spiro Cyclopropanes Based on Meldrum’s Acid by Milling

Abstract

Reaction of 2,2-dimethyl-1,3-dioxane-4,6-dione (Meldrum's acid) with various solid aldehydes in the presence of cyanogen bromide and solid sodium ethoxide (EtONa) leads to the selective and efficient formation of bis-spiro cyclopropanes based on Meldrum's acid at the range of 0°C to room temperature. The products were obtained in good to excellent yields. Structure elucidation is carried out by 1 H NMR, 13 C NMR, FT-IR spectroscopy, mass analyses and X-ray crystallography techniques. A possible mechanism for the formation of products is also discussed under solvent-free condition.

One‐pot, fast cyclopropanation reaction of indandione with various aldehydes in the presence of cyanogen bromide and trimethylamine

“…Moreover, this compound is a suitable brominating and cyanating agent for the bromination and cyanation of imidazoles . More recently, good results were obtained from reaction of cyanogen bromide with aldehyde derivatives and malononitrile, ethyl cyanoacetate, dispiro cyclopropanation of Meldrum's acids by our research team.…”

A review of the synthetic strategies toward spirobarbiturate-fused 3- to 7-membered rings

“…Organic & Biomolecular Chemistry treating 4-(1H-tetrazol-5-yl)benzaldehyde and N,N-dimethylbarbituric acid in the presence of BrCN by using L-(+)-tartaric acid or Et 3 N. Interestingly, conversion of the nitrile group of spirobarbiturate to the corresponding tetrazole did not occur using catalytic amounts of montmorillonite K10, but these transformations were made to synthesize 5-substituted tetrazoles including spirobarbiturates under the same conditions through the [2 + 3] cycloaddition of an azide before spirocyclization. 49 In 2014, Noroozi Pesyan et al described a crossed one-pot reaction of mixed cyclic β-dicarbonyl compounds with aldehydes in the presence of trimethylamine and cyanogen bromide for the selective synthesis of spirobarbiturate-fused dihydrofurans. The products derived from 1,3-dimethyl barbituric acid 6 and 1,3-diethyl thiobarbituric acid 15 as a mixture of cyclic β-dicarbonyl compounds selectively afforded the spirocyclic product in excellent yield.…”

“…A similar strategy was applied to prepare 5-substituted tetrazoles including spirobarbiturates which were constructed by treating 4-(1 H -tetrazol-5-yl)benzaldehyde and N , N -dimethylbarbituric acid in the presence of BrCN by using l -(+)-tartaric acid or Et 3 N. Interestingly, conversion of the nitrile group of spirobarbiturate to the corresponding tetrazole did not occur using catalytic amounts of montmorillonite K10, but these transformations were made to synthesize 5-substituted tetrazoles including spirobarbiturates under the same conditions through the [2 + 3] cycloaddition of an azide before spirocyclization. 49…”