Furan ring opening–pyrrole ring closure: a new synthetic route to aryl(heteroaryl)-annulated pyrrolo[1,2-a][1,4]diazepines

Abstract

A method of synthesis of pyrrolo[1,2-a][1,4]benzodiazepines is described. This method is based on the recyclization of N-(furfuryl)anthranilamides under treatment with an aq. HCl/AcOH system and allows one to form both diazepine and pyrrole rings in one step. The reaction proceeds via furan ring opening into a diketone moiety followed by consecutive interaction of the NH(2)-group with both carbonyl functions. The process is not efficient in the presence of alkyl or aryl groups on amide nitrogen due to competitive furfuryl cation elimination. But alkylation of pyrrolo[1,2-a][1,4]benzodiazepines yields efficiently the corresponding N-alkyl derivatives. Steric effects also prevent cyclization due to reversibility of diazepine ring formation under these reaction conditions. However, the corresponding pyrrolo[1,2-a][1,4]benzodiazepines can be obtained by a stepwise process, i.e., 1) furan ring opening with aq. HCl/AcOH and 2) cyclization of isolated aminodiketones under treatment with glacial acetic acid. Another efficient procedure for the synthesis of pyrrolo[1,2-a][1,4]benzodiazepines consists of acid-catalyzed furan ring opening of N-(furfuryl)-2-nitrobenzamides followed by treatment of the formed nitrodiketone with Fe/AcOH. It leads to a one pot reduction of nitro group to amine, cyclization into diazepine and pyrrole ring formation. This procedure is efficient both for substrates with steric demands and for N-alkyl- or N-aryl-N-(furfuryl)amides. The proposed approach can be also applied to the synthesis of parent pyrrolo[1,2-a][1,4]diazepines or their analogues annulated to heterocycles.

Annelated Pyrrolo[1,2-a][1,4]diazepines in Mannich Reaction

“…Yield 89%; mp 156–157°C. Mp and spectroscopic data were identical to those of a previously described sample .…”

Furan's Gambit: Electrophile‐Attack‐Triggered Sacrifice of Furan Rings for the Intramolecular Construction of Azaheterocycles

“…The acid‐triggered transformations of amides 53 and 57 were shown to furnish pyrrolopyrazines 54 and 58 , respectively. The analogous reaction of β‐alanine N ‐furfurylamide 59 successfully led to the preparation of pyrrolo[1,2‐ a ]diazepine 60 (Scheme ) 26…”

Data Mining for Three-Dimensional Organic Dirac Materials: Focus on Space Group 19

“…We point out the first real material examples in the class of three-dimensional organic crystals hosting isolated Dirac nodes in the electronic structure: C 6 H 7 ClO 3 25 , C 10 H 10 Br 2 Cl 3 NO 2 26 , C 12 H 13 NO 2 27 , C 13 H 12 N 2 O 28 , C 9 H 10 F 3 NO 29 , and C 10 H 12 BrNO 30 . It will be shown that the found Dirac nodes are a consequence of the orthorhombic crystal structure of the space group P 2 1 2 1 2 1 (#19).…”