A New Class of Enehydroxylamino Ketones − (R)‐2‐(1‐Hydroxy‐4,4,5,5‐tetraalkylimidazolidin‐2‐ylidene)ethanones: Synthesis and Reactions

Abstract

Three approaches to the synthesis of (R)‐2‐(1‐hydroxy‐4,4,5,5‐tetraalkylimidazolidin‐2‐ylidene)ethanones 1 are described: (a) condensation of 1,2‐bishydroxylamines with β‐ketoaldehyde synthons, (b) treatment of metallated 1‐hydroxy‐2‐methyl‐4,5‐dihydroimidazoles with esters, and (c) 1,3‐dipolar cycloaddition between 1‐hydroxy‐4,5‐dihydroimidazole‐3‐oxide and DMAD. The reactivity of 1 with electrophiles has been studied. The exocyclic methylene (enamine) carbon atom is shown to be the major site of electrophilic attack. Synthesized chloro‐substituted 1‐hydroxy‐2‐acetylideneimidazolidines react with sodium cyanide to form the corresponding nitriles. Oxidation of these nitriles occurs with formation of persistent vinyl nitroxides, which are of interest as potential paramagnetic ligands. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

Reactions of vicinal aliphatic bis(hydroxylamines) with trifunctionalized methane derivatives

“…When 3-ethoxymethylene-2,4-pentanedione 2c was involved in condensations with BHAs 1a,b neither the expected cyclic ketenaminals 13a,b nor isoxazoline derivatives 14a,b were obtained. The synthesized substances proved to be identical with the products prepared earlier in the reaction of acetoacetaldehyde diethylacetal with BHA 1a,b in acidic medium 13 , i.e. acetylimidazolidine-2-ylidenes 15a,b (Scheme 3).…”

“…In NMR 1 Н spectrum of 22, the singlet signal from aldonitrone proton appears at 7.79 ppm while the corresponding signal from carbon atom in NMR 13 C spectra has a chemical shift of 138.2 ppm that agrees with the spectra of conjugated nitrones. Also, the signals from carbon atoms of cyclohexane CH-groups appear at 66.3 ppm which points at their coupling to sp 2 -nitrogen atom.…”

“…Thus the reaction of cis-1,2-bis(hydroxylamino)cyclohexane 1a with ethyl ester of ethoxymethylenecyanoacetic acid 2а in ethanol at room temperature give 1-hydroxyimidazol-2-ylidene 3a (Scheme 1). NMR 13 С Spectrum of 3a contains characteristic signals of carbon atoms from exocyclic C=C bond at 171.2 and 76.6 ppm, whereas the singlets of ester and amide carbon atoms appeared at 168.0 and 167.1 ppm respectively. Spectral characteristics of compound 3a are similar to those for the earlier prepared derivative 3b 13 .…”

“…13 Taking into consideration the synthesis of physiologically active barbituric acid derivatives, compounds 3a,b were treated with carbamide and thiocarbamide. However, the desired pyrimidine derivatives 4a,b were not observed in this reaction.…”

1,3-Dipolar cycloaddition reaction of 4,5-dihydro-1H-imidazole 3-oxides with alkynes

“…Only aminonitrone A is capable of taking part in the cycloaddition reaction, while N-hydroxyaminoimine B can act only as nucleophile (R 1 = H, Scheme 2). † It is not, therefore, obviously that N-non-substituted derivatives of 4,5-dihydro-1H-imidazole 3-oxide containing a substituent at position 2 of heterocycle can be involved in the reaction of 1,3-dipolar cycloaddition and this reaction is not described for related systems, apart from our previous paper [23].…”