ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL
EXPERIMENTAL PAPER
Sulfated Polyborate Catalyzed Selective Friedlander
Annulation for Synthesis of Highly
Functionalized Quinolines
Anil S. Mali , Abhishek B. Sharma , and Ganesh U. Chaturbhuj
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology,
Mumbai, India
ARTICLE HISTORY Received 13 July 2019; Accepted 22 January 2020
The quinoline moiety is a privileged scaffold because of the wide spectrum of its bio-
logical activities.1,2 Along with the Friedlander annulation, other procedures developed
for the synthesis of quinolines include the following organic name reactions: Skraup,3
Conrad-Limpach-Knorr,4,5 Pfitzinger,6,7 Combes,8,9 and Doebner–Von Miller.10 A num-
ber of acid catalysts have been examined in the past for the Friedlander reaction,
11
13
including Ag3PW12O40, sulfamic acid,12 HClO4-SiO2, Amberlyst-15,14 dodecylphos-
phonic acids,15 SnCl2ꢀ2H2O,16 and NaHSO4-SiO2.17 It is important to recognize the key
role of the catalyst in the Friedlander procedure because the uncatalyzed process may
lead to the formation of the non-Friedlander product.18,19 In keeping with our previous
experiments in catalysis,20–38 we structured the present study to investigate the suitabil-
ity of sulfated polyborate as a catalyst for the Friedlander annulation under different
reaction conditions (Scheme 1). For the preliminary experiments, 2-aminobenzophe-
none (1 mmol) and ethyl acetoacetate (1.2 mmol) were used in a model reaction to
afford ethyl 2-methyl-4-phenylquinoline-3-carboxylate. (Tables 1 and 2).
The reaction does not proceed in the absence of a catalyst at room temperature
(Table 1, entry 1). An increase of the catalyst loading increased the product yield with a
reduction in reaction time (Table 1, entries 2-4). However, catalyst loading beyond
15 wt. % was not advantageous (Table 1, entry 5), so 15 wt. % catalyst loading was
chosen for further work. Temperature also played an important role in our model reac-
tion. The best results were obtained at 80 ꢁC resulting in increased product yield in
shorter reaction time (Table 1, entry 4). We settled on this as the optimum temperature
for performing the reaction.
The effect of several solvents on time and yield of the reaction was ascertained (Table 2).
None of the solvents had any advantage of time and yield over the solvent-free conditions.
Hence, the solvent-free protocol was regarded as the best for cost and environmental
acceptability. In all the experiments the products were isolated by aqueous quenching
followed by filtration and washing the solid products with water.
CONTACT Ganesh U. Chaturbhuj
Department of Pharmaceutical Sciences and
Technology, Institute of Chemical Technology, Mumbai, India-400019.
ß 2020 Taylor & Francis Group, LLC
Chaturbhuj, Ganesh U.
