915124-79-7Relevant academic research and scientific papers
Synthesis and ring cyclization-expansion-contraction reactions of some new 2,2-disubstituted indan-1,3-diones and related compounds
Roxburgh, Craig J.,Banting, Lee
, p. 59 - 74 (2007/10/03)
We have found that the hydrochloride of 2-phenyl-2-[2-(2-piperidyl)ethyl]- 4,5,6,7-tetrahydroindan-1,3-dione 1 possesses marked analgesic activity (100% inhibition referenced to codeine) and report, as part of an extensive synthetic program, the synthesis of 38 new and structurally related compounds. Selective catalytic hydrogenation of the pyridine ring of 2-phenyl-2-[2-(2-pyridyl)ethyl]- indan- 1,3-dione 2 yields the nine-membered nitrogen-containing heterocycle 6 by a novel ring cyclization-expansion reaction. The structural and functional group parameters required for this novel ring-expansion reaction have been extensively and thoroughly investigated through the synthesis of a series of structurally related compounds; principally by modification, substitution, and replacement of the various functionality contained within 2. In addition, we report the synthesis of a series of new 2-methy1-2-(ω-N-phthalimidoalkyl)- indan-1,3-diones 41, 45, and 53, two of which, like the parent 2-phenyl substituted indan-1,3-dione 2, also undergo a novel ring cyclization-expansion reaction to yield eight- and nine-membered nitrogen-containing rings. However, in these cases, further transannular reactions occur to produce the new 5,5- and 5,6-ring-fused nitrogen-containing heterocycles 44, 48 and 51, 52. Hydrazinolysis of the third, 2-methy1-2-(4-N-phthalimidobutyl)-indan- 1,3-dione yields the new azepine-containing ring structure 56 by direct cyclization. Furthermore, some interesting and unexpected chemical properties of the final compounds, which include selective and non-selective pyridine-ring hydrogenations and a few unexpected side reactions, are described. CSIRO 2006.
