ORIGINAL ARTICLE The article was published by ACG Publications http://www.acgpubs.org/journal/organic-communications © October-December 2021 EISSN:1307-6175 DOI: http://doi.org/10.25135/acg.oc.114.2109.2214 Available online: November 25, 2021 Org. Commun. XX:X (202X) X-XX Design, synthesis and antimicrobial screening of some new thienopyrimidines Mahmoud S. Tolba 1,*,# , Mostafa Sayed 1,# , Adel M. Kamal El-Dean 2 , Reda Hassanien 1 , Shaban A. A. Abdel-Raheem 3 and Mostafa Ahmed 1 1 Chemistry Department, Faculty of Science, New Valley University, El-Kharja 72511, Egypt 2 Chemistry Department, Faculty of Science, Assiut University, Assiut 71516, Egypt 3 Soils, Water, and Environment Research Institute, Agricultural Research Center, Giza, Egypt (Received September 20, 2021; Revised November 14, 2021; Accepted, November 16, 2021) Abstract: Heterocyclic compounds play an important role in our life due to their biological importance in the struggle of microorganisms. Herein, a series of novel hybrid compounds of thienopyrimidine with triazine and pyrimidine scaffolds were synthesized starting from difunctionalized compound 5-amino-4-phenyl-2-(p-tolylamino)thieno[2,3- d]pyrimidine-6-carbonitrile (1). Moreover, the diazotization of compound 1 with sodium nitrite in an acidic medium gave the chloro-triazine compound 2 which was subjected to the nucleophilic substitution of chlorine atom with different nucleophiles delivered compounds 3a-5c. Furthermore, the reaction of compound 1 with carbon disulfide led to the formation of dithione derivative 6 which was alkylated with ethyl chloroacetate to give compound 7, on the other hand, the reaction of compound 1 with phenyl isothiocyanate produced 4-imino-3,9-diphenyl-7-(p-tolylamino)-3,4- dihydropyrimido[4',5':4,5]thieno [2,3-d]pyrimidine-2(1H)-thione (8), while acylation of the amino group in compound 1 with acetic anhydride gave compound 9. All synthesized compounds were characterized by elemental and spectral analysis techniques (IR, 1 H NMR, 13 C NMR, Mass spectroscopy). Furthermore, the synthesized compounds were tested for their antimicrobial activity against different strains of bacteria and fungi, and the results obtained showed good to moderate activity with almost all the strains. Keywords: Thienopyrimidne; synthesis; antibacterial; antifungal; triazine. ©2021 ACG Publication. All right reserved. 1. Introduction The building of new heterocyclic compounds containing nitrogen and sulfur atoms attracts the interest of many organic chemists due to their biological importance in various aspects 1,2 . Among heterocyclic compounds containing nitrogen and sulfur, thienopyrimidines play an important role in the drug research as a result of strong biological activity they exhibit 3–5 which may be attributed to the * Corresponding author: E-Mail: mahmoud.tolba@sci.nvu.edu.eg Phone: +201027297981 #These authors (M S. Tolba and M. Sayed) contributed equally to this manuscript.