Synthesis of 8-substituted xanthines and their oxidative skeleton rearrangement to 1-oxo-2,4,7,9-tetraazaspiro[4,5]dec-2-ene-6,8,10-triones

The synthesis of a number of 8-(dialkylamino)- and 8-alkoxyxanthines (3 and 6, respectively) is described. Treatment of 3 with m-chloroperoxybenzoic a cid (m-CPBA) gave:by a novel rearrangement 3-(disubstituted amino)-4,7,9-tr imethyl-1-oxo-2,4,7,9-tetraazaspiro[4,5]dec-2-ene- 6,8,10-triones 10. Also, the corresponding 3-alkoxy-subtituted spiro compounds 12 were obtained by an analogus treatment of 8-alkoxyxanthines 6. In attempts to elucidate a te ntative mechanism for this rearrangement 8[(dialkylamino)methyl]caffeines 7 when treated with m-CPBA did not undergo the rearrangement but only yielde d the expected N-oxide derivatives 16. This result seems to indicate that a necessary structure element for this rearrangement to occur is an atom wit h an unshared pair of electrons to be attached to the 8-position of the inv estigated xanthines. In agreement with this statement is the fact that N-ox ides of 8-[(dialkylamino)methyl]caffeines 16 do not undergo the novel rearr angement but rather give the expected Meisenheimer rearrangement or the Cop e elimination depending upon reaction conditions.