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

Victoria V Lipson; Tetiana L Pavlovska; Nataliya V Svetlichnaya; Anna A Poryvai; Nikolay Yu Gorobets; Erik V Van der Eycken; Irina S Konovalova; Svetlana V Shiskina; Alexander V Borisov; Vladimir I Musatov; Alexander V Mazepa

doi:10.3762/bjoc.15.101

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

Beilstein J Org Chem. 2019 May 6:15:1032-1045. doi: 10.3762/bjoc.15.101. eCollection 2019.

Authors

Affiliations

¹ SSI "Institute for Single Crystals" of National Academy of Sciences of Ukraine, Nauky Ave. 60, Kharkiv 61074, Ukraine.
² Antidiabetic Drug Laboratory, SI "V.Ya. Danilevsky Institute for Endocrine Pathology Problems", Academy of Medical Sciences of Ukraine, 10, Alchevskih St., Kharkiv 61002, Ukraine.
³ Chemistry Department, V.N. Karazin Kharkov National University, Kharkov 61022, Ukraine.
⁴ Laboratory for Organic & Microwave-Assisted Chemistry (LOMAC), Katholieke Universiteit Leuven, Celestijnenlaan 200F, B-3001 Leuven, Belgium.
⁵ Peoples' Friendship University of Russia (RUDN University) 6 Miklukho-Maklaya street, Moscow, 117198, Russia.
⁶ Enamine Ltd., 23 Chervonotkats'ka str., Kyiv 01003, Ukraine.
⁷ A.V. Bogatsky physico-chemical institute of the National Academy of Sciences of Ukraine, 86, Lustdorfskaya doroga, 65080, Odessa, Ukraine.

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.