Closure of the pyridine ring in the combes quinoline synthesis (Review)

Synthesis of novel annelated systems based on the interaction and reactivity estimation of amino‐1,5‐benzodiazepin‐2‐ones with dimethyl‐2‐oxoglutaconate

“…It is confirmed that the formation of a new pyridine ring takes place at the adjacent position with respect to the primary amine group of the starting compound. However, the regiochemical outcome of cyclization reaction for asymmetrically substituted aromatic amines is unpredictable [3, 15]. To get more insight into the nature of the studied cyclization process, the theoretical investigation of the electronic structure of the starting compounds was carried out.…”

“…Considering the reaction mechanism of the Doebner‐von Miller quinoline synthesis, it was shown [2, 3, 15] that cyclization reaction involves a stepwise mechanism. The cyclocondensation step is based on the electrophilic addition to the carbon atom of the aromatic ring [2, 15]. This step determinates the regiochemical features of the reaction.…”

Syntheses of Isoquinoline and Substituted Quinolines in Charged Microdroplets

“…The Combes reaction3b, 15 is another type of acid‐catalyzed synthesis of quinolines (Figure 4, top) by the condensation of aniline 12 and β‐diketone 8 . In the bulk phase, the synthesis is carried out in two steps 15b. The first step involves the formation of Schiff base 13 by the reaction of aniline 12 and a β‐diketone 8 .…”

Interaction of derivatives of 7-amino-1,5-benzo-diazepin-2-ones with α,β-unsaturated ketones

“…Thus on interacting 7-amino-4-phenylbenzodiazepinone 1a with dimethyl 2-oxoglutaconate two products were obtained, tetracyclic [1,4] The structures of compounds 2 and 3 were confirmed by 1 H and 13 C NMR spectra (Tables 2 and 3). In the 1 H NMR spectrum of compound 3 three singlet signals were observed for the aromatic protons of the benzene and pyridine rings, two singlets for the methoxycarbonyl groups at 4.05 and 4.09 ppm.…”

“…It was also shown that quantum-chemical calculations of the minimal values of the local ionization energy (I min ) on the electron density surface of the molecules and the resonance stabilization energy of the initial amines fortunately demonstrate the tendency of activation and deactivation of the benzene ring [2, 3]. The possibility of using quantumchemical calculations to determine the direction of ring formation of quinolines was followed in [4]. Continuing the investigations of the synthesis of condensed systems of 1,5-benzodiazepinone, we considered in the present work the direction of closure of the pyridine ring on interacting derivatives of 7-amino-4-phenyl(or methyl)-1,3,4,5-tetrahydro(or 1,3-dihydro)-2H-1,5-benzodiazepin-2-ones with α,β-unsaturated ketones under the conditions of the modified Debner-Müller reaction.…”