Some Transformations of TertiaryN-Furfurylamides of Aromatic and Heteroaromatic Carboxylic Acids under Acidic Conditions

Abstract

A c i d -C a t a l y z e d T r a n s f o r m a t i o n s o f t e r t -N -F u r f u r y l c a r b o x a m i d e sAbstract: Acid-catalyzed transformations of tertiary N-furfurylamides of ortho-amino substituted aromatic and heteroaromatic carboxylic acids accompanied by elimination of the furfuryl moiety are investigated.Furan derivatives have been widely applied as useful building blocks in carbo-and heterocyclic compound chemistry for many years and there are numerous reviews devoted to their synthetic application. 1 We have studied the usage of furan compounds for annelated heterocyclic systems synthesis. 2In a preceding paper 3 we presented a new method for the synthesis of pyrrolo[1,2-a]diazepinone derivatives, based on acid-catalyzed transformations of N-One of the advantageous features of our method is the simultaneous formation both of diazepine and pyrrole rings as a result of a furan ring recyclization (Scheme 1).Some pyrrolo[1,2-a][1,4]diazepine derivatives show a wide range of biological activity, including anxiolytic, 4 sedative and antiepileptic activities; 5 they also affect the central nervous system. 6 A number of pyrrolo[1,2-a] [1,4]diazepinone derivatives possess analgesic action, 7 and act as antibacterial 8 and anti-fungal agents with high specificity towards dermatophytes. 9Since diazepine derivatives are of interest in the search for new biologically active compounds and precursors for the manufacture of new medicines, an extension of the developed approach towards the preparation of new pyrrolodiazepines became our main aim.Herein we report our results on acid-catalyzed transformations of tertiary N-furfuryl-containing amino amides of aromatic and heteroaromatic carboxylic acids with an amino function in the ortho position to a carboxy group.As starting compounds we used tertiary amides of orthoaminobenzoic acids 3, which were prepared from secondary furfurylamines 1 according to Scheme 2. 3 We also used N2-substituted N2-(5-methyl-2-furylmethyl)-3-aminothieno[2,3-b]pyridine-2-carboxamides 6, which were synthesized from pyridinethiones 4 and the corresponding furfurylchloroacetamides 5 under Thorpe-Ziegler conditions (Scheme 3). 3,10

One-pot synthesis of 1-alkyl- 4,5-dihydro-6H-pyrrolo[1,2-a]- [1,4]benzodiazepin-6-one

“…The 1 H NMR spectrum and mass spectrum were identical to those presented in our previous work [2]. 50% yield; mp 195-196°C (mp 195-196°C [1] …”

“…We have recently reported a synthesis of derivatives of pyrrolo[1,2-a][1,4]diazepine based on the acidcatalyzed recyclization of N-(5-methyl-2-furyl)-3-aminothieno[2,3-b]pyridinecarboxamides and N-(5-methyl-2-furyl)anthranilamides [1,2]. This method involves the simultaneous formation of diazepine and pyrrole rings.…”

“…1-Methyl-4,5-dihydro-6H-pyrrolo[1,2-a][1,4]benzodiazepine (1a) was obtained in 49% yield; mp 230-231°C (mp 230-231°C [2]). The 1 H NMR spectrum and mass spectrum were identical to those presented in our previous work [2].…”

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

“…Yield 77%; mp 249–251°C. Mp and spectroscopic data were identical to those of a previously described sample .…”

“…From this perspective, we had described the interesting method for the preparation of pyrrolo[1,2‐ a ][1,4]diazepinones annelated with benzene or thieno[2,3‐ b ]pyridine moiety by the furan ring recyclization of N ‐furfurylanthranylamides and 3‐aminothieno[2,3‐ b ]pyridine‐2‐carboxamides under acid conditions (Scheme ) . The important feature of the method is a simultaneous formation of both diazepine and pyrrole rings.…”