Synthesis and characterization of some novel 4-furyl substituted 3-imidazoline 3-oxides

Novel 4-furyl substituted 3-imidazoline 3-oxides were synthesized by the reaction of 2-bromo-1(2-furanyl)ethanone oxime with aromatic amines and aldehydes, including formaldehyde, using one pot procedures involving the reactions of in situ formed α-amino oximes with aldehydes and also by one pot procedures involving the reactions of in situ formed imines with α-halo oximes.


Introduction
Cyclic nitrones, which are heterocyclic compounds containing an azomethine N-oxide group, have a wide range of synthetic potentialities. 1 This is due to the fact that, as in the case of heterocyclic N-oxides 2 , the N-oxide oxygen atom activates them with respect to electrophilic, nucleophilic and radical reagents.In addition, the ability of the nitrones to undergo 1,3-and 1,4cycloaddition reactions makes it possible to use them in the synthesis of various heterocyclic systems, including natural compounds. 3,4n the literature, some papers have been found about the substituted 3-imidazoline 3-oxides containing phenyl, methyl, methoxy, amino, nitro, nitroso, hydroxy groups as substituents at different positions. 5The synthesis of 1,4-diaryl and 1,2,4-triaryl imidazoline 3-oxides containing a phenyl ring as aryl groups have been reported 6a-d and these N-oxides have been used as dipoles in [3+2] cycloaddition reactions with various dipolarophiles to obtain biologically important isoxazolidine and isoxazoline rings.7a-f There is no data about the 4-furyl substituted 3-imidazoline 3-oxides in the literature.In the present work, a series of novel 4-furyl substituted 3-imidazoline 3-oxides have been synthesized and will be used as dipoles in [3+2] cycloaddition reactions in forthcoming studies because of the importance of the furan ring.Furan, as one of the representative five-membered heterocycles, is found in many naturally occurring compounds. 8Besides this, oxidation of furan rings gives useful intermediates for the synthesis of new compounds. 9,10onobromination of acetyl furan 1 produces 2-bromo-1-(2-furanyl)ethanone 2 11 (Scheme 1).Then, its reaction with hydroxylamine sulfate 3 yields 2-bromo-1-(2-furanyl)ethanone oxime 4 12 .Substitution reaction of 2-bromo-1-(2-furanyl)ethanone oxime 4 with an aromatic amine 5 gives amino oxime 6 and the condensation reaction of amino oxime 6 with an aldehyde 7 affords an imino oxime 8. Cyclization reaction of this imino oxime 8 yields 4-furyl substituted 3imidazoline 3-oxides 9 in a similar way as in literature.6c The overall synthetic pathway is shown in Scheme 1 and the results are summarized in Table 1.

Scheme 1
Cyclizations were carried out in ethanol at room temperature.In the 1 H NMR spectrum of nitrone 9a, CH 3 protons belonging to a tolyl group gave a singlet at δ 2.20.CH 2 protons at C-4 and C-5 appeared as triplets at δ 4.65 and 5.25, respectively.Protons of the tolyl group show two doublets at δ 6.44 and 7.07.On the other hand, furyl group protons appeared as a doublet of doublets at δ 6.58; a singlet at δ 7.48 and a doublet at δ 7.79.
In the 1 H NMR spectrum of 2-arylsubstituted nitrone 9b, CH 3 protons belonging to the tolyl group gave a singlet at δ 2.15.CH 2 protons at C-5 gave a doublet of doublets at δ 4.73 and 5.05, the CH proton between two nitrogen atoms at C-2 appeared as a doublet of doublets at δ 6.06.Protons of the tolyl group show two doublets at δ 6.43 and 6.95.On the other hand, furyl group protons appeared as a doublet of doublets at δ 6.54 and two doublets at δ 7.47 and 7.71, respectively.Protons of phenyl group appeared as multiplets at δ 7.30-7.37and 7.51-7.57.

Conclusions
In summary, some novel 4-furyl substituted 3-imidazoline 3-oxides were synthesized.The methods that were used in this study are easy and short to synthesize potentially biologically active compounds.It has been thought that these new compounds can have some biological activities because of the imidazoline and furan moieties presented in their structures.Also, these novel 4-furyl substituted 3-imidazoline 3-oxides will be used as dipoles in [3+2] cycloaddition reactions in forthcoming studies.

2-Bromo-1-(2-furanyl)ethanone (2)
. 11 Under a nitrogen atmosphere, bromine (38 mmol) was added dropwise over a 30 min.period to an ice-cold solution of 3.303 g (30 mmol) of 2acetylfuran 1 in 18 ml of dioxane-ether (1:2).The reaction mixture was warmed to ambient temperature and stirred for 12 h., then quenched with 20 ml of saturated aqueous ammonium chloride.The organic extract was dried over anhydrous magnesium sulfate and the solvent removed under reduced pressure.The residue was purified by column chromatography using hexane-ethyl acetate as eluent and the product 2 was obtained as a light yellow semisolid (3.97 g, 70%, mp: 28-32 o C).