Quinazolines microwave-assisted synthesis

Eguchi S (2006) Quinazoline Alkaloids and Related Chemistry. 6 113-156 Erd lyi M (2006) Solid-Phase Methods for the Microwave-Assisted Synthesis of Heterocycles. 1 79-128... 

A similar rapid microwave one-pot synthesis of substituted quinazolin-4-ones was also reported, which involved cyclocondensation af anthranilic acid, formic acid (or an orthoester) and an amine under solvent-free conditions (Scheme 3.37)61. A complimentary approach was adopted to synthesise 4-aminoquinazolines in very good yields, involving the reaction of aromatic nitrile compounds with 2-aminobenzonitrile in the presence of a catalytic amount ofbase (Scheme 3.38)62. The reactions were performed in a domestic microwave oven and required only a very short heating time. A microwave-assisted synthesis of a variety of new 3-substituted-2-alkyl-4-(3H)-quinazolinones using isatoic anhydride, 2-aminobenzimidazole and orthoesters has also been described (Scheme 3.38)63. 

Keywords Aza-Wittig reaction Quinazolinone annelation Quinazoline alkaloids -Microwave-assisted synthesis Solid-phase synthesis... 

The topical synthetic methodologies such as iminophosphorane mediated synthesis (aza-Wittig methodology), microwave-assisted synthesis, solid-phase synthesis, and application of organometalUc reagents, etc., will be discussed retrospectively focusing on the pathways to quinazoline, quinazoline-4-one and their derivatives. 

The fourth chapter Quinazoline Alkaloids and Related Chemistry by Shoji Eguchi provides a perspective review focusing on developements of the synthetic methodologies and their synthetic applications. A brief historical background, aza-Wittig methodology, microwave-assisted synthesis, solid-phase... 

R. Saari, J.-C. Toermae, T. Nevalainen, Microwave-assisted synthesis of quinoline, isoquinoline, quinoxaHne and quinazoline derivatives as CB2 receptor agonists, Bioorg. Med. Chem. 19 (2011) 939-950. 

An efficient microwave-assisted multi-step synthesis of8//-quinazolino [4,3-b] quina-zolin-8-one has been investigated by Besson and co-workers77. The synthesis involved two Niementowski condensations starting from substituted anthranilic acids (Scheme 3.49). Both homogeneous and heterogeneous conditions were studied in an effort to develop a convenient synthesis of the desired compounds. The solventless procedure allowed easier access to the quinazolino[4,3-fi]quinazolin-8-ones and gave better yields than the method performed in the presence of solvents. However, the procedure with solvents would offer the possibility of investigating the microwave-assisted solid-phase synthesis of these quinazolinones, which would faciltate purification of the final products. 

In 1998, Rad-Moghadam and Khajavi47 developed a microwave-assisted three-component cyclocondensation for the synthesis of quinazolin-4(3//)-ones. 

Scheme 19 Microwave-assisted one-pot synthesis of 2,3-disubstituted 3ff-quinazolin-4-ones...

Tu S, Li C, Li G et al (2007) Microwave-assisted combinatorial synthesis of polysubstituent imidazo[l, 2-a]quinoline, pyrimido[l, 2-a]quinoline and quinolino[l, 2-a]quinazoline derivatives. J Comb Chem 9 1144-1148... 

Microwave-Assisted Multi-Component One-Pot Synthesis of Quinazolines. 125... 

Scheme Microwave-assisted Niementowski quinazoline synthesis [158,159]...

Quinazoline synthesis using carbon dioxide under mild conditions has been developed by Mizimo et al. [210,211]. The simple solvent free synthesis of quinazoline-2,4-diones imder supercritical carbon dioxide and a catalytic amount of base provides an industrially benign approach and meets the challenges of green chemistry as previously discussed the microwave-assisted and/or soHd-phase syntheses (see Sects. 2.2 and 2.3). 

---