Synthesis of 3-bromotetronamides via amination of 3,4-dibromofuran-2(5H)-one

Abstract

Este trabalho descreve a síntese de dez tetronamidas em bons rendimentos através da reação da 4-dibromofuran-2(5H)-ona, obtida do furfural, com aminas primárias e secundárias. As aminas aromáticas foram mais toleradas que as alifáticas e as heteroaromáticas. Foram determinadas as estruturas cristalinas de cinco derivados.This work describes the direct synthesis of 3-bromotetronamides in good yields through the reaction of 3,4-dibromofuran-2(5H)-one, obtained from furfural, with primary and secondary amines. Aromatic amines were more tolerated than aliphatic and heteroaromatic ones. The X-ray structures of five derivatives are described. Keywords: enaminones, tetronamides, butenolides IntroductionThe synthesis of functionalized tetronamides is a theme of ongoing research activity, and this interest is due to the synthetic applications of such compounds, mainly in heterocyclic synthesis.1 A particular class of synthetically useful tetronamides are the 3-halo derivatives. However, most of the available protocols for the synthesis of 3-halotetronamides are based on the direct halogenation of a preformed enaminone, employing halogenation's reagents such as ICl, NBS, Br 2 , I 2 , I(py) 2 BF 4 and benzyltrimetylammonium dichloroiodate (BTMA.ICl 2 ). 2Cyclic enaminones are especially attractive in the formation of bicyclic compounds.3 In this context, tetronamides have embedded in their structure the N-C=C-C=O enaminone moiety, and recently they have emerged as a latent acyclic enaminone in the formal aza-[3+3] cycloaddition reaction. 4 However, the synthesis of 3-halotetronamides unsubstituted at position 5 is scarcely described, being limited to the reaction of α-halotetronic acid with an amine 5 or by direct halogenation of tetranamides.6 Thus, practical synthetic approaches to this class of compound would be beneficial.In our ongoing investigation on the chemistry of enaminones, 7 we envisioned herein a direct route to 3-bromotetronamides (4-amino-3-bromo-2(5H) furanones), which are a special class of cyclic compound because they present both aspects mentioned above, i.e., the embedded enaminone moiety, and the bromide atom at the alpha position. Besides, this study represents an approach to 3-bromotetronamides from furfural, an attractive starting material obtained from renewable biomass. In this way, the furfural derivative of choice was the 3,4-dibromofuran-2(5H)-one 1, which is easily prepared in 70% overall yield by the reaction of furfural with bromine in water, affording mucobromic acid (commercially available also). 8 This late was reduced affording 1 in 87-96% yield, Scheme 1, employing a recently described method by Bellina and Rossi. 9 It should be pointed out that the reactions where 1 is employed as electrophile is scarcely described, being limited to palladium cross-coupling reactions, 10 or only to morpholine as nucleophile and expensive base (Cs 2 CO 3 ). 11 Results and DiscussionThe amination of 1 has proved to be a difficult task due to its propensity to forming polymeric material, probably th...

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