Novel (2-amino-4-arylimidazolyl)propanoic acids and pyrrolo[1,2- c]imidazoles via the domino reactions of 2-amino-4-arylimidazoles with carbonyl and methylene active compounds

Abstract

The unexpectedly uncatalyzed reaction between 2-amino-4-arylimidazoles, aromatic aldehydes and Meldrum's acid has selectively led to the corresponding Knoevenagel-Michael adducts containing a free amino group in the imidazole fragment. The adducts derived from Meldrum's acid have been smoothly converted into 1,7-diaryl-3-amino-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-ones and 3-(2-amino-4-aryl-1H-imidazol-5-yl)-3-arylpropanoic acids. The interaction of 2-amino-4-arylimidazoles with aromatic aldehydes or isatins and acyclic methylene active compounds has led to the formation of pyrrolo[1,2-c]imidazole-6-carbonitriles, pyrrolo[1,2-с]imidazole-6-carboxylates and spiro[indoline-3,7'-pyrrolo[1,2-c]imidazoles], which can be considered as the analogues of both 3,3'-spirooxindole and 2-aminoimidazole marine sponge alkaloids.

Keywords: (2-amino-4-arylimidazolyl)propanoic acid; 2-amino-4-arylimidazole; 3,3’-spirooxindoles; Meldrum’s acid; isatin; multicomponent reactions; pyrrolo[1,2-c]imidazole.

Figure 1

2-Aminoimidazole alkaloids from marine sponges.

Figure 2

The Knoevenagel–Michael adduct [24] and expected products.

Scheme 1

The three component condensation of imidazo[1,2-a]pyridine, aldehydes and Meldrum’s acid described by Gerencsér at al. [31].

Figure 3

Molecular structure of 1-([1,1'-biphenyl]-4-yl)-5-oxo-7-phenyl-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-3-aminium 2,2,2-trifluoroacetate 9i according to X-ray diffraction data. Thermal ellipsoids of atoms are shown at 50% probability level.

Scheme 2

Two forms of cation 9i.

Figure 4

Molecular structure of 3-(2-amino-4-phenyl-1H-imidazol-5-yl)-3-(p-tolyl)propanoic acid 11b according to X-ray diffraction data. Thermal ellipsoids of atoms are shown at 50% probability level.

Scheme 3

Three forms of the compound 11b in the crystal phase.

Scheme 4

Synthesis of the mixture of compounds 13 and 14.

Figure 5

Molecular structure of aminoimidazo[1,2-c]pyrrole 16a according to X-ray diffraction data. Thermal ellipsoids of atoms are shown at 50% probability level.

Scheme 5

Resonance structures of 16a.

Figure 6

3,3’-Spirooxindole alkaloids.

Figure 7

Molecular structure of aminoimidazo[1,2-c]pyrrole 19a according to X-ray diffraction data. Thermal ellipsoids of atoms are shown at 50% probability level.

Scheme 6

Resonance structures of 19a.