Azavinyl Azomethine Ylides from Thermal Ring Opening of α-Aziridinohydrazones:  Unprecedented 1,5-Electrocyclization to Imidazoles

Abstract

Michael-type addition of aziridinecarboxylates to 1,2-diaza-1,3-butadienes under solvent-free conditions (SFC) resulted in the formation of alpha-aziridinohydrazone adducts. In toluene under reflux, alpha-aziridinohydrazones gave imidazoles in moderate to good yields. Such a reactivity pattern is explained by 1,5-electrocyclization of azavinyl azomethine ylide generated through thermal ring opening of alpha-aziridinohydrazones.

Cultivating the Passion to Build Heterocycles from 1,2‐Diaza‐1,3‐dienes: the Force of Imagination

“…To the best of our knowledge, such a reactivity of aziridine-derived azomethine ylides is unprecedented and represents the first example of 1,5-electrocyclization of azavinyl azomethine ylides in which direct C-N bond formation occurs instead of the observed C-C bond formation (Scheme 25). [45] Scheme 25. Postulated mechanism for the formation of imidazoles 126 by 1,5-electrocyclization of azavinyl azomethine ylides 124 obtained from DD 1f,i and carboxyaziridines 121.…”

One‐Pot Synthesis of Imidazole‐4‐Carboxylates by Microwave‐Assisted 1,5‐Electrocyclization of Azavinyl Azomethine Ylides

“…Michael‐type 1,4‐conjugate addition of DDs 1a – f (either as an isolated compound or in situ generated from the corresponding chlorohydrazone by treatment with TEA in the case of 1a , c ) with the primary amine gives α‐aminohydrazone A ,4e which in turn condenses with the aldehyde partner to yield iminium ion B . Microwave‐assisted heating may result in the formation of conjugated azavinyl azomethine ylide7,8 C , which undergoes 1,5‐electrocyclization to 2,3‐dehydroimidazole‐4‐carboxylate D and, eventually, aromatization with loss of carbamate or urea, thus affording the desired 3 H ‐imidazole‐4‐carboxylates 2a – w , by analogy to the formation of DD‐derived α‐imidazol‐1‐yl esters we have recently disclosed 5,6…”

“…We have reported a significant extension of the 1,5‐electrocyclization of conjugated azavinyl azomethine ylides5,6 to substituted imidazole‐4‐carboxylates by one‐pot sequential reaction between DDs and primary amines, followed by microwave‐assisted heating in the presence of aldehydes. The method is efficient and straightforward and does not require isolation of intermediates.…”

“…To follow up our work, we envisioned replacing α‐aminoesters with primary aliphatic or aromatic amines, which would allow more general access to simpler imidazole‐4‐carboxylates in a one‐pot fashion without the need of isolating reaction intermediates. Initial attempts with α‐aminohydrazones under the same reactions conditions5,6 did provide the desired imidazole‐4‐carboxylates in very modest yields. Because charged chemical species or intermediates are well known to benefit from microwave irradiation, as in the case of 1,3‐dipolar cycloadditions,3 we reasoned that our 1,5‐electrocyclization of DD‐derived azavinyl azomethine ylides could be likewise enhanced by employing microwave heating.…”

“…Recently, we reported the successful synthesis of α‐imidazol‐1‐yl esters through 1,5‐electrocyclization of azavinyl azomethine ylides that were ultimately derived from 1,2‐diaza‐1,3‐dienes (henceforth DDs)4 and aziridines5 or by sequential reaction with α‐aminoesters and aldehydes 6. In particular, conjugated azavinyl azomethine ylides were generated by heating DD‐derived α‐aminoester hydrazones in toluene at reflux in the presence of aldehydes, and they were found to undergo an original 1,5‐electrocyclization into imidazoles 5,6. To follow up our work, we envisioned replacing α‐aminoesters with primary aliphatic or aromatic amines, which would allow more general access to simpler imidazole‐4‐carboxylates in a one‐pot fashion without the need of isolating reaction intermediates.…”