Hypervalent Iodine Mediated Dehydrogenative Oxidation of 5,6-dihydropyrimido[4,5-d]pyrimidines to Pyrimido[4,5-d]pyrimidines

Nitrogen-based aza-heterocycles are very important class of organic compounds widely found in natural products. Nitrogen containing small molecules is widely used as precursors for the preparation complex molecules in pharmaceutical, agrochemical, dye, and polymer industries. In the recent research, many nitrogen-containing heterocycles has also been acted as organocatalysts in various asymmetric syntheses. Pyrimido[4,5-d]pyrimidines, a [6,6]-fused pyrimidine derivative displayed a wide-range of biological properties. Pyrimidopyrimidine-based molecules are widely used in the synthesis medicinal and pharmaceutical compounds. Several pyrimidopyrimidine-based molecules exhibited a range of biological activities, including anticancer, antiviral, antifungal, antioxidant, antitumor, antimalarial, and anti-inflammatory properties. Due to their diverse applications in medicinal and material chemistry, scientists across the world are being paid efforts for the development of new processes for the synthesis of this class of compounds.

Nowadays, hypervalent iodine reagents are considered as versatile reagents in organic transformations due to their ready availability, non-toxic, operational simplicity and environmentally friendly nature. These reagents are particularly useful in oxidation reactions, functional group transfer, cyclization, and C-C/C-N bond formation, providing an efficient and environmentally friendly pathway in organic synthesis

In this paper, hypervalent iodine mediated dehydrogenative oxidation of 5,6-dihydropyrimido[4,5-d]pyrimidines to pyrimido[4,5-d]pyrimidines has been discussed. A variety of pyrimido[4,5-d]pyrimidines has been obtained in good to excellent yields (85-98%) by the oxidation of 5,6-dihydropyrimido[4,5-d]pyrimidines using PhI(OAc)₂ as an oxidizing reagent in toluene at 80 ⁰C. The protocol is operationally simple and tolerated a numbers of functional groups, leading to diverse pyrimido[4,5-d]pyrimidines of biological importance.