The scheme of this work involves synthesis and evaluation the biological activity of some new 2-amino-5-mercapto-1,3,4-thiadiazole compounds derived from thiosemicarbazide as starting material. This work is divided into three parts: First part: this part involved synthesizing Oxazepine derivatives [3], [4], [6], [7] which derived from the reaction of compounds [0], [1], [2], [5] with different organic compounds. The following reaction steps is shown in scheme [I], [II]. Second part: This part involved synthesizing oxazole derivative [10] which derived from the reaction of compounds [0], [1], [8], [9] with different organic compounds. The following reaction steps is shown in scheme [III]. Third part: this part involved evaluate the biological activity of some synthesized compounds for their antimicrobial activity against three strains of pathogenic microorganism, Gram positive bacteria Staphylococcus aureus and two types of Gram negative bacteria Escherichia coli, Pseudomonas. The results revealed that some of these compounds showed measurable activity as shown in table (3-11).