Heterocyclization of N,N′-disubstituted p-phenylenediamines with cyclich β-diketones and formaldehyde. Synthesis of new pyrido[2,3-g]quinoline derivatives

Abstract

Three-component condensation of N,N′-dibenzyl-p-phenylenediamines with cyclic β-diketones and formaldehyde under mild conditions resulted in selective formation of a series of new dispiro derivatives of pyrido[2,3-g]quinoline.Three-component condensation of aromatic amines with aldehydes and cyclic β-dicarbonyl compounds provides a convenient one-step procedure for the synthesis of fused polynuclear heterocyclic systems. This reaction was successfully used to prepare various functionalized derivatives of piperidine [1], benzo[f]quinoline [2], benzoacridine [3, 4], phenanthroline [5], pyrazolo[3,4-b]quinoline [6], pyrimido[4,5-b]quinoline [7], furo[3,4-e]pyrazolo[3,4-b]pyridine [8], and other heterocyclic systems [9]. In all cases, the starting compounds were electron-rich aromatic monoamines.We previously showed that spiro compounds of the 1,2,3,4-tetrahydroquinoline series can readily be obtained by condensation of N-monosubstituted anilines I containing an electron-donating substituent R 1 with formaldehyde (II) and cyclic β-diketones III (Scheme 1) [10]. We presumed that analogous three-component condensation may be performed with aromatic diamines. In this case, the second amino group should not only activate the reaction due to its pronounced electron-donor properties but also participate in condensation, giving rise to new polynuclear nitrogencontaining heterocycles. To verify this assumption, we synthesized a series of symmetric N,N′-disubstituted p-phenylenediamines Ia-If and brought them into three-component condensation with formaldehyde (II) and cyclic β-diketones IIIa and IIIb of the cyclohexane-1,3-dione series. The reactions were carried out in ethanol by heating for a short time in the absence of a catalyst. In fact, the products were those formed from one aromatic diamine molecule and two β-diketone and two formaldehyde molecules. On the basis of the 1 H NMR data, the isolated compounds were assigned the structure of pyrido[2,3-g]quinoline derivatives VIa-VIl (Scheme 2). It should be noted that alternative isomeric heterocyclization products, 4,7-phenanthroline derivatives like VII, were not detected in the reaction mixtures.A probable mechanism of the heterocyclization process is shown in Scheme 3. Spirocyclic pyrido-[2,3-g]quinoline derivatives VIa-VIl are formed via initial reaction of formaldehyde (II) with β-diketone

Pyridoacridines in the 21st Century

“…Here again there are no natural substances that include this skeleton, however there are synthetic examples. The reaction of 6‐aminoquinoline 204 with cyclohexane‐1,3‐diones and formaldehyde produces partially reduced pyrido[3,2‐ a ]acridinones 205 (R 2 = H, Scheme ) . Inclusion of an araldehyde in the reaction mixture, instead of the formaldehyde, produces corresponding products 205 (R 2 = Ar; 10 examples, 65–81 %) …”

“…The reaction of 6-aminoquinoline 204 with cyclohexane-1,3-diones and formaldehyde produces partially reduced pyrido[3,2-a]acridinones 205 (R 2 = H, Scheme 68). [127] Inclusion of an araldehyde in the reaction mixture, instead of the formaldehyde, produces corresponding products 205 (R 2 = Ar; 10 examples, 65-81 %). [128] Scheme 68.…”

“…A simple synthesis of hexahydropyrido[3,2-a]acridinones 205. [127] Benzylic carbanions react with nitroarenes under mild conditions in the presence of DBU and trialkylchlorosilanes to form tetra-and pentacyclic azaarenes. This reaction was used to make a range of fused systems from 6-nitroquinoline including cyano-206 and methoxycarbonyl-207 pyrido[3,2-a]acridines (Scheme 69).…”

Recent advances in the chemistry of imine-based multicomponent reactions (MCRs)

“…Condensation of aromatic aldehydes with dimedone and primary arylamines under acidic condition leads to the efficient synthesis of 9,10-diaryl-3,3,6,6-tetramethyl decahydro acridinediones 16. 24 From the preceding discussion, it is clear that the outcome of three-component reaction of dimedone, aldehyde and amine leads to diverse molecular scaffolds. 24 From the preceding discussion, it is clear that the outcome of three-component reaction of dimedone, aldehyde and amine leads to diverse molecular scaffolds.…”

Selectivity in metal ions mediated C–N bond formation reactions of 8‐aminoquinoline derivatives

“…Several naturally occurring drug molecules contain quinoline rings as their constituents . Aminoquinoline derivatives are useful in cyclisation reactions for ring expansion and for the synthesis of steroids . Multiple possibilities exist to obtain cyclised products from intramolecular cyclisation reactions of 8‐aminoquinoline derivatives.…”