a b s t r a c tThe Diels-Alder reaction of (E)-2-styrylchromones with a pyrimidine ortho-quinodimethane is reported for the first time. These cycloaddition reactions afford mixtures of two regioisomeric tetrahydroquinazoline-substituted chromones in moderate to excellent global yields. Irrespective of the substituents on the 2-styrylchromones, the 2-(7-aryl-4-methoxy-2-methyl-5,6,7,8-tetrahydroquinazolin-6-yl)chromone derivatives are always the major isomers.Ó 2012 Elsevier Ltd. All rights reserved.2-Styrylchromones are a small group of naturally-occurring heterocyclic compounds. Since the isolation of the first natural 2-styrylchromone in 1986, 1 that showed to be a potent cytotoxic agent, a large number of publications have emerged involving the synthesis and transformation of this type of chromone derivatives. 2,3 A literature survey revealed that 2-styrylchromones have been typically prepared from ortho-hydroxyacetophenones where the aldol condensation/oxidative cyclization and the BakerVenkataraman methods are the most promising approaches for the synthesis of a large variety of derivatives. As a result, a series of styrylchromone analogues were synthesized and several biological properties have been assigned to them, including antiallergic, antioxidant, antifungal, anti-inflammatory, and antitumor activities.
3,4Besides the synthesis, studies on the reactivity of 2-styryl chromones and their use as synthons in the preparation of other important classes of compounds have been highlighted in the literature. Most important is their reaction with hydrazines to afford several pyrazole derivatives 5,6 and also their interception in pericyclic reactions as dienes, dienophiles, and also as dipolarophiles. In the former case, the synthesis of several xanthone-type compounds was performed by cycloaddition reaction with maleic anhydride, N-arylmaleimides, and cyclic and acyclic enamines. [7][8][9][10][11] The reactions of these vinylchromones with diazomethane 12 and sodium azide 13,14 are the examples of their use as dipolarophiles to prepare 2-pyrazolines and 1,2,3-triazoles, respectively. To the best of our knowledge, the use of 2-styrylchromones as dienophiles in Diels-Alder reactions has only been reported by us in a couple of papers involving the symmetric ortho-benzoquinodimethane. 15,16 This extremely reactive diene was used in the synthesis of a large number of naphthylchromones and constitutes a versatile intermediate in other cycloaddition reactions. 17 Much less attention has been given to the chemistry of heteroaromatic analogues of ortho-quinodimethanes. The multi-step route, moderate yields, and a large number of secondary products are the limitations in the use of dienes in the preparation of these intermediates. [17][18][19] However, heterocyclic ortho-quinodimethanes are an attractive tool in the design of novel heteropolycyclic compounds. Following our interest on the chemistry of ortho-quino dimethanes [20][21][22][23] and on the synthesis of heterocyclic compounds, we decided to study the Diels-A...
