An efficient and direct protocol for the preparation of 1-amidoalkyl-2-naphthols 1a–f employing a multi-component, one-pot condensation reaction of 2-naphthol, heterocyclic aldehydes, and amides in the presence of anhydrous zinc chloride under solvent-free conditions is described. The thermal solvent-free offer advantages such as shorter reaction times, simple work-up and excellent yield. Ring closure of 1a–f gave the pyrazolyl- and indolyl oxazine derivatives 2a–f. On the other hand, the reaction of 2-naphthol, aldehydes, and ammonia solution gave the dipyrazolyl- and di-indolyl oxazine derivatives 3a,b. Some of the newly synthesized compounds showed promising antibacterial and anti-H5N1 activities.