Reaction of α-Oxoketene-N,S-arylaminoacetals with Vilsmeier Reagents:  An Efficient Route to Highly Functionalized Quinolines and Their Benzo/Hetero-Fused Analogues

Abstract

A simple, highly efficient, and regioselective synthesis of functionalized quinolines through Vilsmeier cyclization of a variety of alpha-oxoketene-N,S-anilinoacetals has been reported. The cyclization is found to be facile with N,S-acetals bearing strongly activating groups on aniline, whereas yields of quinolines are moderate in other cases. The reaction could also be extended for the synthesis of substituted tricyclic benzo[h]quinoline, pyrido[2,3-h]quinoline, 4,7-diphenylphenanthroline, and tetracyclic quino[8,7-h]quinoline by performing a Vilsmeier reaction on N,S-acetals derived from 1-naphthylamine, m-phenylenediamine, o-phenylenediamine, and 1,5-diaminonaphthalene, respectively. A few of the newly synthesized quinolines are subjected to further transformation to afford 2-unsubstituted (Raney-Ni/Ethanol), quinoline-5,8-quinone (NBS/H(2)SO(4)), or 2-alkyl/aryl aminoquinolines through sequential m-CPBA oxidation to the corresponding (2-methylsulfonyl)quinoline followed by replacement with appropriate amines. Similarly, cycloannulation of a few 2-methylthio-3-benzoylquinolines with hydrazine hydrate under microwave irradiation afforded the corresponding substituted and fused pyrazolo[3,4-b]quinolines in excellent yields, whereas TBTH/AIBN-mediated cyclization of the corresponding 3-(2-bromobenzoyl)-2-methylthioquinolines yielded the corresponding benzothiopyrano-fused quinolines through radical translocation.

A Convenient and Simple Synthesis of Densely Functionalized Cyclopenta[cd]azulenes and Cyclopenta[ef]heptalenes

“…First, for a model study, we selected 3a, which was treated with POCl 3 in DMF at 08 for 2 h to provide diethyl cyclopenta[cd]azulene-1,4-dicarboxylate (5a) in a yield of 94% after purification by column chromatography ( Table 2, Entry 1). The reaction proceeds via VilsmeierÀHaack formylation [7], more selectively at C(3), followed by intramolecular cyclization, which was confirmed by spectral analysis. To examine the scope of this reaction, we employed various 4-substituted azulene derivatives, 3b -3f, 4a and 4b, to obtain the desired cyclopenta[cd]azulenes 5a -5c in low-to-high yields ( Table 2, Entries 2 -8).…”

Synthesis of 2,3‐dihydro‐6H‐1‐oxa‐3a‐aza‐phenalene and its benzo/hetero‐fused analog

“…The use of a-oxoketene dithio-acetals in the synthesis of various heterocyclic molecules is well documented in the literature [12,13]. However, there is no report about its uses in the synthesis of tricyclic analogs of benzoxazines.…”

Aplicação de α-oxoceteno ditiocetais em síntese orgânica

“…42 As enaminonas 85 reagiram com solução do reagente de Vielsmeier (dimetilformamida-POCl 3 ou dimetilacetamida-POCl 3 ) através de uma ciclização intramolecular com eliminação de água, obtendo-se as 2-tiometilquinolinas 86 com rendimento de 25-98% (Esquema 34). Além disso, os α-oxoceteno ditioacetais 84 reagiram com a o-fenilenodiamina, a m-fenilenodiamina e o 1,5-diaminonaftaleno para produzir aminoquinolinas.…”