Synthesis of benzo[f]quinoline derivatives by condensation of N-arylmethylene-2-naphthylamines with acetylcyclohexane and 1-acetylcyclohexene

Abstract

N-Arylmethylene-2-naphthylamines react with acetylcyclohexane and 1-acetylcyclohexene under mild conditions to afford 2-aryl-2-(2-naphthylamino)ethyl cyclohexyl and 1-cyclohexenyl ketones, respectively. Under more severe conditions (110oC), the reaction is accompanied by cyclization with formation of 3-aryl-1-cyclohexyl (or 1-cyclohexenyl)benzo[ f ]quinolines. Proper choice of the amount of catalyst, temperature, and reaction time allows isolation of intermediate 3-aryl-1-cyclohexyl(or 1-cyclohexenyl)-3,4-dihydrobenzo[ f ]quinolines. Quinoline derivatives are structural analogs of alkaloids [1], enzyme inhibitors [2], and antibiotics [3]; therefore, they should exhibit versatile biological activity. In addition, these compounds are good antioxidants [4] and antirads [5] for polymeric materials. Interest in quinoline derivatives and analogs continuously increases. Some benzoquinolines were found to possess good complexing [6] and fluorescent properties [7].A known procedure for the synthesis of benzo[ f ]-quinolines is based on the condensation of Schiff bases derived from 2-naphthylamine with various aliphatic, aromatic, and heterocyclic methyl ketones [8312]. It was found that the formation of benzo[ f ]-quinolines is a multistep process [12]. The reaction of N-arylmethylene-2-naphthylamines with methyl ketones of the cycloaliphatic series has been studied poorly. We previously synthesized benzo[ f ]quinoline derivatives by condensation of N-arylmethylene-2-naphthylamines with acetylcyclohexane and 1-acetylcyclohexene [13,14]. In doing so, either no intermediate products were isolated at all or they were isolated in very small amounts. In the present work we performed condensations of acetylcyclohexane (I) and 1-acetylcyclohexene (II) with Schiff bases IIIa3 IIIh of the 2-naphthylamine series using larger amounts of the initial reactants and tried to isolate and examine intermediate products by varying the reaction conditions.Condensations of Schiff bases with ketones are catalyzed by acids. Proton addition to a Schiff base yields the corresponding cation in which the positive charge is delocalized over the azomethine nitrogen and carbon atoms. Therefore, such cations readily take up even weakly nucleophilic ketones. The reaction mechanism is analogous to the acid-catalyzed aldol addition pattern. The reaction involves the methyl group in methyl ketone, so that the latter acts as CH acid. Amino ketones IVa3IVf and Va3Vg thus formed are the first intermediate products in the synthesis of benzo[ f ]quinolines (see scheme). The double bond in 1-acetylcyclohexene is conjugated with the carbonyl group; as a result, polarization of the C=O bond increases, and protons in the acetyl group become more labile. Therefore, the yields of amino ketones from 1-acetylcyclohexene are greater, and the condensation occurs at a lower temperature, as compared to acetylcyclohexane (Table 1). Amino ketones IVa3IVf and Va3Vg were obtained by heating the reactants in ethanol at 40360oC in the presence of a catalytic amount of hydrochlor...

A highly selective method for the synthesis of 1,3-diarylbenzo[f]quinoline derivatives catalyzed by silver triflate

“…For example, some benzoquinolines exhibit antibacterial activity [1,2], uridine diphosphate-glucuronosyl transferase activity [3,4], antimicrobial activity [5], antimalarial activity [6], agonistic activity [7], and antipsychotic activity [8]. In view of the importance of these compounds, several methods for the synthesis of benzoquinolines were developed by Kozlov [9][10][11][12][13][14][15] and other groups [2,[16][17][18][19][20][21][22][23][24][25][26][27][28]. Among these known procedures, the imino-Diels-Alder reaction (or Povarov reaction) of N-arylimines (Schiff bases) with electron-rich dienophiles is one of the most convenient methods for quinoline preparation.…”

A highly selective method for the synthesis of 1,3-diarylbenzo[f]quinoline derivatives catalyzed by silver triflate

“…For example, some benzoquinolines exhibit antibacterial activity [1,2], uridine diphosphate-glucuronosyl transferase activity [3,4], antimicrobial activity [5], antimalarial activity [6], agonistic activity [7], and antipsychotic activity [8]. In view of the importance of these compounds, several methods for the synthesis of benzoquinolines were developed by Kozlov [9][10][11][12][13][14][15] and other groups [2,[16][17][18][19][20][21][22][23][24][25][26][27][28]. Among these known procedures, the imino-Diels-Alder reaction (or Povarov reaction) of N-arylimines (Schiff bases) with electron-rich dienophiles is one of the most convenient methods for quinoline preparation.…”

A highly selective method for the synthesis of 1,3-diarylbenzo[f]quinoline derivatives catalyzed by silver triflate

“…For example, some benzoquinolines exhibit antibacterial activity [1,2], uridine diphosphate-glucuronosyl transferase activity [3,4], antimicrobial activity [5], antimalarial activity [6], agonistic activity [7], and antipsychotic activity [8]. In view of the importance of these compounds, several methods for the synthesis of benzoquinolines were developed by Kozlov [9][10][11][12][13][14][15] and other groups [2,[16][17][18][19][20][21][22][23][24][25][26][27][28]. Among these known procedures, the imino-Diels-Alder reaction (or Povarov reaction) of N-arylimines (Schiff bases) with electron-rich dienophiles is one of the most convenient methods for quinoline preparation.…”

A highly selective method for the synthesis of 1,3-diarylbenzo[f]quinoline derivatives catalyzed by silver triflate

“…For example, some benzoquinolines exhibit antibacterial activity [1,2], uridine diphosphate-glucuronosyl transferase activity [3,4], antimicrobial activity [5], antimalarial activity [6], agonistic activity [7], and antipsychotic activity [8]. In view of the importance of these compounds, several methods for the synthesis of benzoquinolines were developed by Kozlov [9][10][11][12][13][14][15] and other groups [2,[16][17][18][19][20][21][22][23][24][25][26][27][28]. Among these known procedures, the imino-Diels-Alder reaction (or Povarov reaction) of N-arylimines (Schiff bases) with electron-rich dienophiles is one of the most convenient methods for quinoline preparation.…”