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

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].

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

References

<A NAME="RF16006SS-1">1</A> Goto S. Tsuboi H. Kagara K. Chem. Express  1993,  8:  761 

<A NAME="RF16006SS-2">2</A> Kagara K, Goto S, and Tsuboi H. inventors; JP  1,025,767.  ; Chem. Abstr. 1989, 111, 97274

<A NAME="RF16006SS-3">3</A> Mohri S. J. Synth. Org. Chem., Jpn.  2001,  59:  514 

<A NAME="RF16006SS-4">4</A> Merck Index   12th ed.:  Merck & Co., Inc.; Whitehouse Station NJ: 1996.  p.7897 

<A NAME="RF16006SS-5">5</A> Merck Index   12th ed.:  Merck & Co., Inc.; Whitehouse Station NJ: 1996.  p.1512 

<A NAME="RF16006SS-6">6</A> Merck Index   12th ed.:  Merck & Co., Inc.; Whitehouse Station NJ: 1996.  p.3489 

<A NAME="RF16006SS-7">7</A> Pastor G. Blanchard C. Montginoul C. Torreilles E. Giral L. Texier A. Bull. Soc. Chim. Fr.  1975,  1331 

<A NAME="RF16006SS-8">8</A> Khalifa M. Osman AN. Ibrahim MG. Ossman ARE. Ismail MA. Pharmazie  1982,  37:  115 

<A NAME="RF16006SS-9">9</A> Michman M. Patai S. Wiesel Y. Org. Prep. Proced. Int.  1978,  10:  13 

<A NAME="RF16006SS-10">10</A> Lange NA. Sheibley FE. Org. Synth. Coll. Vol. II   John Wiley & Sons; London: 1943.  p.79 

<A NAME="RF16006SS-11">11</A> Vorbrüeggen H. Krolikiewicz K. Tetrahedron  1994,  50:  6549 

<A NAME="RF16006SS-12">12</A>

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.

<A NAME="RF16006SS-13">13</A> Mizuno T. Okamoto N. Ito T. Miyata T. Tetrahedron Lett.  2000,  41:  1051 

<A NAME="RF16006SS-14">14</A> Mizuno T. Okamoto N. Ito T. Miyata T. Heteroat. Chem.  2000,  11:  428 

<A NAME="RF16006SS-15">15</A> Mizuno T. Ishino Y. Tetrahedron  2002,  58:  3155 

<A NAME="RF16006SS-16">16</A> Mizuno T. Iwai T. Ishino Y. Tetrahedron Lett.  2004,  45:  7073 

<A NAME="RF16006SS-17">17</A> Haruki E. In Organic and Bio-organic Chemistry of Carbon Dioxide   Inoue S. Yamazaki N. Kodansha Ltd.; Tokyo: 1981.  p.5 

<A NAME="RF16006SS-18">18</A> Haruki E. Arakawa M. Matsumura N. Otsuji Y. Imoto E. Chem. Lett.  1974,  427 

<A NAME="RF16006SS-19">19</A> Hori Y. Nagano Y. Fukuhara T. Teramoto S. Taniguchi H. Nippon Kagaku Kaishi  1987,  1408 

<A NAME="RF16006SS-20">20</A> Pérez ER. Silva MO. Costa VC. Rodrigues-Filho UP. Franco DW. Tetrahedron Lett.  2002,  43:  4091 

<A NAME="RF16006SS-21">21</A> Mavrovic I. In Kirk-Othmer Encyclopedia of Chemical Technology   2nd ed., Vol. 21:  Mark HF. Interscience Publishers; New York: 1970.  p.37