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Synthesis 2007(16): 2524-2528  
DOI: 10.1055/s-2007-983808
PAPER
© Georg Thieme Verlag Stuttgart · New York

Solvent-Free Synthesis of Quinazoline-2,4(1H,3H)-diones Using Carbon Dioxide and a Catalytic Amount of DBU

Takumi Mizuno*, Masatoshi Mihara, Takeo Nakai, Toshiyuki Iwai, Takatoshi Ito
Osaka Municipal Technical Research Institute, 1-6-50, Morinomiya, Joto-ku, Osaka 536-8553, Japan
Fax: +81(6)69638049; e-Mail: tmizuno@omtri.city.osaka.jp;
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Publication History

Received 26 September 2006
Publication Date:
24 July 2007 (online)

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Abstract

An ideal reaction system, which is aimed at sustainable chemistry, was developed. Under solvent-free conditions, quinazoline-2,4(1H,3H)-diones were obtained in good to excellent yields from 2-aminobenzonitriles with only carbon dioxide (1 bar) and a catalytic amount of base (DBU or DBN). For example, 6,7-dimethoxyquinazoline-2,4(1H,3H)-dione, which is a key intermediate of several drugs (Prazosin, Bunazosin, and Doxazosin) was synthesized successfully in 97% yield [DBU (0.2 equiv), CO2 (1 bar), 120 °C].

Key words

carbon dioxide - carbonylation - cyclization - catalytic - quinazoline - quinazolidinone

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The use of the chemical fixation of carbon dioxide in fine chemicals production is of importance both in terms of the environmental problems of global warming and the effective utilization of chemical resources. Carbon dioxide is an attractive C1 building block in organic synthesis as it is highly abundant, inexpensive, nontoxic, and nonflammable. However, due to the inert nature of carbon dioxide, efficient processes for chemical fixation remain significant synthetic challenges.