A facile and convenient synthesis of an interesting N‐(1H‐pyrazol‐5‐yl)‐hexahydroquinoline‐3‐carbonitrile and octahydropyrazolo[4′,3′:5,6]pyrimido[1,2‐a]quinoline‐6‐carbonitrile derivatives via the versatile readily accessible cyclic enaminones incorporating pyrazole moiety was accomplished.
A novel series of interesting spiro cyclic 2-oxindole derivatives of N-(1H-pyrazol-5-yl)hexahydroquinoline derivatives were prepared via the versatile readily accessible cyclic β-enaminones incorporating pyrazole. Antimicrobial evaluations were performed on the prepared compounds. Most of these compounds exhibited high to moderate antimicrobial activity. INTRODUCTION The Michael addition reaction has been widely used in organic synthesis for its CC bond forming ability. Useful application of a tandem Michael addition is seen in the total synthesis of the antimicrobial compound Claenone. 1 In this respect, Yamada et al. 1 managed to construct a norbornane ring using two sequential Michael additions. The Michael reaction is also used in other reactions. The best known example is the Robinson annulation, where the Michael addition occurs as the first step. 2 This sequence of Michael addition followed by intramolecular Aldol has proved to be one of the most important chemical reactions introduced into in the area of steroid chemistry as shown in Woodward's synthesis of cortisone. 2 In addition, the spiro-oxindole ring system is one of the most distinguished heterocyclic ring systems, which constitutes the core structural element of many biologically active molecules that received an extensive synthetic interest. 3-17 Moreover, quinoline and its derivatives exist in a variety of biologically significant compounds possessing anticancer, 18 antioxidants, 19 anti-inflammatory 20 and antimicrobial activities. 21-23 Considering the versatile bioactivities of the two structures of spiro-oxindole and 2-amino-tetrahydroquinolin-5-one, we expect that the integration of the two scaffolds into a spiro-oxindole incorporating 2-amino-tetrahydroquinolin-5-one can result in the discovery of new active drugs. RESULTS AND DISCUSSION In continuation to our interest on the chemistry of enamines 24-27 as well as Michael addition we report herein a new series of novel spirocyclic 2-oxindole derivatives of N-(1H-pyrazol-5-yl)hexahydroquinoline derivatives via the cyclocondensation reaction of 3cyanomethylidene-2-oxindoles and 3-(substituted pyrazol-5-yl)-5,5-dimethylcyclohex-2-enone. The required cyclic -enaminoketones incorporating pyrazole moiety 3, were prepared via the reaction of the dimedone 1 with the aminopyrazole derivatives 2 using a catalytic amount of trichloroacetic acid as a catalyst under solvent-free conditions. Scheme 1. Synthesis of enamines 3a,b The possibility of [3+3] atom combination of the prepared -enaminones 3a,b with 3cyanomethylidene-2-oxindoles 4a-c through Michael addition reaction was studied. Thus, the reaction of compound 3a with compounds 4a-c in the presence of piperidine resulted in the formation of spiroquinolines 7a-c. Compounds 7 were formed due to the initial addition of the -CH of 3a to the activated double bond in 4, to yield Michael adducts 5 that readily cyclized into 6 that tautomerized into 7. (cf. Scheme 2). The structures of the novel hexahydroquinolines 7 were assigned based on the spectro...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.