Pd/C as an efficient heterogeneous catalyst for carbonylative four-component synthesis of 4(3H)-quinazolinones

Pd/C as an efficient heterogeneous catalyst for carbonylative four-component synthesis of 4(3H)-quinazolinones

Catal. Sci. Technol., 2015, 5,4474-4480
DOI: 10.1039/C5CY00907C, Paper

Kishore Natte, Helfried Neumann, Xiao-Feng Wu

http://pubs.rsc.org/en/Content/ArticleLanding/2015/CY/C5CY00907C?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2Fcy+%28RSC+-+Catalysis+Science+%26+Technology+latest+articles%29#!divAbstract

http://www.rsc.org/suppdata/c5/cy/c5cy00907c/c5cy00907c1.pdf

A relatively mild, operationally simple, phosphine-free and recyclable catalytic system for the carbonylative synthesis of 4(3H)-quinazolinones with 2-iodoanilines, trimethyl orthoformate, and amines as the substrates has been developed.

Quinazolinones are of interest in the fields of pharmaceuticals and medicinal chemistry. 

The application of palladium on activated charcoal (Pd/C) as a heterogeneous catalyst was 

investigated for the carbonylation of 2-iodoanilines with trimethyl orthoformate and amines 

via a multicomponent reaction approach, which provided excellent yields of 4(3H)-quinazolinones. 

It avoids the use of expensive phosphine ligands with an additional advantage of catalyst recovery. 

Furthermore, >5 new quinazolinone scaffolds containing the trifluoroethyl group were introduced

 by this procedure; gram scale experiments were successfully performed as well.

General Procedure for the Synthesis of Quinazolinone: A 12 mL vial was charged with 10% Pd/C (1 mol%; 10 mg), 2-iodoaniline (1 mmol) and a stirring bar. Then, aniline (1.1 mmol), trimethyl orthoformate (2 mmol), DiPEA (3 mmol), and toluene (3 mL) were injected by syringe under argon. The vial (or several vials) was placed in an alloy plate, which was transferred into a 300 mL autoclave of the 4560 series from Parr Instruments® under argon atmosphere. After flushing the autoclave three times with CO, a pressure of 10 bar CO was adjusted at ambient temperature. Then, the reaction was performed for 20 h at 110 oC. After the reaction finished, the autoclave was cooled down to room temperature and the pressure was released carefully. The solution was filtered through whatmann filter paper and washed the reaction mixture with acetone (2-3 ml). After evaporation of the organic solvent the residue was adsorbed on silica gel and the crude product was purified by column chromatography using n-heptane/ethyl acetate (70:30) as eluent. 

Procedure for Catalyst Recycling The catalyst obtained after filtration was thoroughly washed with distilled water (3-5 mL) and then with methanol, acetone and ethyl acetate (3-5 mL) to remove any traces of organic material if present. The resulting catalyst was dried in an oven at 80 °C for 6 h and was then used for the next cycle. 

Pd/C as an efficient heterogeneous catalyst for carbonylative four-component synthesis of 4(3H)-quinazolinones

Kishore Natte,^a   Helfried Neumann^a and   Xiao-Feng Wu*^a  

*

Corresponding authors

^a

Leibniz-Institut für Katalyse an der Universität Rostock, Albert-Einstein-Straße 29a, 18059 Rostock, Germany
E-mail: xiao-feng.wu@catalysis.de

Catal. Sci. Technol., 2015,5, 4474-4480

DOI: 10.1039/C5CY00907C

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