ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL
021, VOL. 53, NO. 2, 138–144
2
EXPERIMENTAL PAPER
Friedl a€ nder Synthesis of Novel Polycyclic Quinolines Using
Solid SiO /H SO Catalyst
2
2
4
a
b
a
Jeanluc Bertrand
,
a
, Iv ꢀa n Britoc , and Cristian O. Salas
a
a
Departamento de Qu ꢀı mica Org ꢀa nica, Facultad de Qu ꢀı mica y de Farmacia, Pontificia Universidad
b
Cat ꢀo lica de Chile, Santiago de Chile, Chile; Departamento de F ꢀı sico-Qu ꢀı mica, Facultad de Ciencias
c
Qu ꢀı micas, Universidad de Concepci ꢀo n, Concepci ꢀo n, Chile; Departamento de Qu ꢀı mica, Facultad de
Ciencias B ꢀa sicas, Universidad de Antofagasta, Antofagasta, Chile
ARTICLE HISTORY Received 15 May 2020; Accepted 13 August 2020
In the current milieu of synthetic organic chemistry, environmental, economic and industrial
issues have caused practitioners to re-examine the significance and value of heterogeneous
1
,2
3,4
catalysts. Among the most useful of these is silica gel/sulfuric acid (SSA), readily pre-
5,6
pared and easily deployed in the synthesis laboratory. Given the widely-recognized useful-
ness of quinolines in drug design and in diversity studies,
7,8
9–12
we turned our attention to
the preparation of the title compounds using SSA as an improved catalyst for the
Friedlander reaction. To the best of our knowledge, this is the first such report. We made
and rigorously characterized novel polycyclic quinoline derivatives by the SSA catalyzed con-
densation of 2-aminoarylketones 1 with 1,2- or 1,3-dicarbonyl compounds. Thus 1 reacted
with 1,2-cyclohexanedione or with 1,3-cyclohexanedione to give 2,3-dihydroacridin-4-ones 3
(Scheme 1) and 3,4-dihydroacridin-1-ones 5 (Scheme 2), respectively.
We optimized our reaction conditions using the preparation of compound 3a as our
model, and the results are summarized in Table 1. Using thin layer chromatography to
check the reaction endpoint, we examined the model with respect to catalyst (10 mol%),
solvent, temperature and time (see Experimental section). Based on yields, the best
results (Table 1, entry 5) employed SSA in methanol at reflux for 2 hours and resulted
in 3a in 92% yield. The structure of 3a was supported by elemental analysis, by FT-IR
and NMR spectra, and by single-crystal X-ray diffraction studies (Figure 1).
In extending our preparations to the other compounds designated in Scheme 1, we
found that yields were excellent (mean 92%). The crude products were isolated by sim-
ple filtration and were purified by recrystallization from ethyl acetate. No chromato-
graphic procedure was required to obtain pure products.
Application of our SSA catalyzed Friedlander procedure was also made to the reac-
tions shown in Scheme 2, in which the diketone was 1,3-cyclohexanedione. Similar
results were obtained in this family of compounds. The range of yields was 90-95%.
The compounds were rigorously characterized, and the single crystal X-ray structure of
5
c is shown in Figure 2.
CONTACT Rajendran Satheeshkumar
Departamento de Qu ꢀı mica Org ꢀa nica, Facultad
de Qu ꢀı mica y de Farmacia, Pontificia Universidad Cat ꢀo lica de Chile, 702843, Santiago de Chile, Chile
Supplemental data for this article can be accessed here.
ß 2021 Taylor & Francis Group, LLC
Satheeshkumar, Rajendran
