Chem. Pharm. Bull. 54(3) 403—405 (2006)

compounds. They exhibit antianaphylactic, oral hypotensive and antiulcer properties. 2-Benzoxepine moiety is present in many useful neuroleptic (pinoxepin), antidepressant (spiroxepin) and anti-inflammatory agents (isoxepac and oxepinac). The synthesis of 2-benzoxepines having different functionalities is thus necessary. As a part of our program related to the discovery of novel bioactive compounds we recently required to prepare some 2-benzoxepines (as they are reputed for their bioactivity) and to study their antibacterial property. We connected the program with our on-going endeavor on Morita–Baylis–Hillman chemistry which has already been utilized by us for the synthesis of various bioactive molecules. We have observed that treatment of Morita–Baylis–Hillman adducts 1 with HCHO in the presence of silica supported perchloric acid (HClO4·SiO2) or Amberlyst-15 in CH2Cl2 under reflux afforded the corresponding 2-benzoxepines 2 in good yields (Chart 1). Previously, only one method was developed for the conversion of 1 into 2 using concentrated H2SO4 which is not ecologically acceptable. The reagent may also cause charring of the reaction mixture. The yields of the products were reported to be in the range of 44—61%. In recent year, economic and environmental concerns encourage the application of heterogeneous catalysts in organic transformations. These catalysts make the processes clean, safe, high-yielding and inexpensive. We have discovered that HClO4·SiO2 and Amberlyst-15 are two efficient catalysts for conversion of the Morita–Baylis–Hillman adducts 1 into the corresponding 2-benzoxepines 2 by treatment with HCHO. Initially we treated 1f (R R H, R Et) (1 mmol) with HCHO (1 mmol) in the presence of different solid acid catalysts (100 mg each) in CH2Cl2 under reflux for 2 h (Table 1). HClO4·SiO2 and Amberlyst-15 were only found to be effective but HClO4·SiO2 was better and within 1.5 h it afforded an yield of 80% of the product. When the reaction was carried out with Amberlyst-15 at room temperature a conversion of only 48% was observed after 3 h and the yield was not increased even after overnight treatment. On the other hand, HClO4·SiO2 afforded no product at room temperature. To make a series of 2-benzoxepines (Table 2) HClO4·SiO2 was utilized for a time of 1.5—2 h under reflux to form the products with the yields of 66—82% while under the similar conditions the other catalyst Amberlyst-15 required somewhat more time (0.5 h) and the yields were also somewhat low March 2006 403