6533b7cffe1ef96bd1258f88

RESEARCH PRODUCT

Reactions of Piperazin-2-one, Morpholin-3-one, and Thiomorpholin-3-one with Triethyl Phosphite Prompted by Phosphoryl Chloride: Scope and Limitations

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description

The reaction of the title lactams with triethyl phosphite prompted by phosphoryl chloride provided six-membered ring heterocyclic phosphonates or bisphosphonates. These novel scaffolds might be of interest as building blocks in medicinal chemistry. The course of the reaction was dependent on the structure of the used substrate. Thus, morpholin-3-one and thiomorpholin-3-one readily provided the corresponding 1,1-bisphosphonates (compounds 1, 2, 7, 14 and 16), whereas the protection of their nitrogen atom resulted in the formation of dehydrophosphonates (compounds 5, 6, and 8). Piperazin-2-one reacted differently yielding mixture of cis- and trans- piperazine-2,3-diyl-bisphosphonates (compounds 10 and 11). Since cytosine could be considered as an analogue of piperin-2-one, its ditosyl derivative 18 was used as a substrate affording compound 19 being a product of phosphite addition to double bond. In dependence of their structures, hydrolysis of the obtained diethyl phosphonates resulted either in corresponding cyclic phosphonic acids or in the degradation of carbon-to-phosphorus bond.