Substitutional effects on the reactivity and thermal stability of dihydropyrimidinones

•Two different series of dihydropyrimidinones were synthesized.•The effects of the various substituents were investigated using TGA, DSC and DFT.•Azidation reaction was used to assess the ease of the substitution reaction.•The molecular structures of the compounds were confirmed using NMR and SCXRD. One of the advantages of dihydropyrimidinones (DHPMs) is the molecular diversity that could be achieved through their synthesis from a three-component reaction by varying the starting reaction materials. Differences in substituted functional groups could lead to varying reactivities and thermal stability amongst the analogues. In this study, two different classes of DHPMs were synthesized and the effects of the various substituents on the DHPM ring were investigated. The compounds were structurally characterized using single-crystal X-ray diffractometry, 1H, 13C, COSY, HSQC and HMBC NMR techniques, FT-IR and High Resolution Mass Spectrometry (HRMS). N1 methylation of the DHPM was found to increase the thermal stability of the series of DHPMs investigated, which is an added advantage in thermal reactions. The nature of the alkyl substituent of the ester group at position 5 of the DHPM was also found to affect the ease of the nucleophilic substitution reaction during the functionalization of the DHPMs. A complementary DFT study aided in understanding the above results as well as to compare the general stability of the range of compounds. [Display omitted]