A simple and efficient approach was developed to synthesize symmetrical/unsymmetrical bis[1,3]oxazines using ammonium acetate with controllable substitution patterns in a one-pot fashion. In a representative crystal structure, the [1,3]oxazine ring is in a distorted semichair conformation with C2-carbon and nitrogen atoms residing above and below the naphthalene plane, leading to strain in the ring that allows ring-opening polymerization to take place. A few of the derivatives were found to possess anticancer activity. This current modest protocol affords numerous advantages such as mild reaction condition, shorter reaction time, operational simplicity, and excellent yield. Copyright © 2015 Taylor & Francis Group, LLC.