Регіоселективність алкілування 2-оксо(тіо)-3-феніл-тієно[2,3-d]піримідинонів

Abstract

The elaboration of easy and affordable highly selective methods for the synthesis of thieno[2,3-d]pyrimidine derivatives, which operate on none toxic reagents and energy-saving techniques, is an urgent task of organic chemistry. Among the large number of functional derivatives of the title heterocycle, the most interesting objects for our research group are 2- oxo-(thio)-3-phenyl-thieno[2,3-d]pyrimidinones, which contain several reactive nucleophilic centers (nitrogen, oxygen and sulfur atoms), which determines their ambidenties in reactions with electrophilic reagents. Many approaches to the introduction of substituents and functional groups into the thieno[2,3-d]pyrimidine system have been developed, among which the alkylation reactions are the most common. In our previous study, we theoretically predicted the regioselectivity of the alkylation of 2-oxo(thioxo)-3-phenyl-thieno[2,3- d]pyrimidin-4-ones and investigated possible influencing factors. In continuation of this study, in order to reliably validate the results of previous computer simulations, we alkylated the title heterocyclic system with a number of alkylating reagents under the same synthetic conditions, which involve the alkylation of the most thermodynamically advantageous anionic form. 2-Oxo-(thio-)-3-phenyl-5,6,7,8- tetrahydro[1]benzothieno[2,3-d]pyrimidinones were used as starting compounds. To provide alkylation conditions for the most thermodynamically advantageous anion, the starting compounds were heated with excess of potassium hydroxide in ethanol until completely dissolving. The resulting solution of the corresponding potassium salts was cooled and kept atroom temperature, after which an excess of alkylating reagent was added and kept at room temperature an additional time. As a result of research, a preparative method of alkylation of 2-oxo-(thio-)-3-phenyl- 5,6,7,8-tetrahydro[1]benzothieno [2,3-d] pyrimidinones was developed, which corresponds to the principles of green chemistry (operates with none toxic solvents, easy to perform and does not require long-term heating). The sixteen new previously undescribed thieno[2,3- d]pyrimidine derivatives were obtained. Keywords: 2-oxo-(thio)-3-phenyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidinones; alkylation; regioselectivity; thermodynamically advantageous anion; energy saving approaches.