Chemistry of adamantanes and related compounds. Diazotization of endo-7-aminomethylbicyclo[3.3.1]nonan-3-one and endo-3-aminomethylbicyclo[3.3.1]nonane

Abstract

Diazotization of nonan-3-one (1) under various conditions was investigated.In a protic medium (acetic acid), 3-methylbicyclo[3.3.1]non-2-en-7-one (3) was the only major product. With an aprotic system (benzene), 4-protoadamantanone (4) was the principal product, accompanied by 3. endo-3-Aminomethylbicyclo[3.3.1]nonane (2) was diazotized under the same sets of conditions yielding (a) elimination products, 3-methylbicyclo[3.3.1]non-2-ene (5) and 3-methylenebicyclo[3.3.1]nonane (6); and (b) substitution products, 3-acetoxymethylbicyclo[3.3.1]nonane (7) and 3-hydroxymethylbicyclo[3.3.1]nonane (8). Catalytic hydrogenation of 3 resulted in reductive cyclization to 1-adamantanol in excellent yield. Sodium borohydride reduction of 3 furnished 3-methyl-7-hydroxybicyclo[3.3.1]non-2-ene (9), which was converted to l-methyl-2oxaadamantane (10) on exposure to a Lewis acid catalyst or hydrogen and palladium. The stereochemical and mechanistic aspects of the various transformations are treated.

Synthesis, in Vitro Pharmacology, and Molecular Modeling of Very Potent Tacrine−Huperzine A Hybrids as Acetylcholinesterase Inhibitors of Potential Interest for the Treatment of Alzheimer's Disease

“…Reaction of enones rac-13d,g,i, previously prepared in our group, 23 and of the new ones rac-13e,f,h with 2-aminobenzonitrile (14) catalyzed by AlCl 3 in 1,2-dichloroethane under reflux gave rise in moderate to excellent yields to the corresponding racemic aminoquinolines rac- [21][22][23][24][25][26]. These compounds were transformed into the corresponding hydrochlorides and crystallized from the appropriate solvent (see Experimental Section).…”

“…The organic solvents were removed under reduced pressure, and the residue was filtered. The solid residue was submitted to column chromatography [silica gel (12 g), hexane/ AcOEt/MeOH mixtures] to give rac- [21][22][23][24][25][26][27][28][29][30][31]. A solution of rac-21-31 in MeOH was treated with a solution of HCl (0.55 N solution in Et2O, 3 equiv), and the solvent was evaporated to give rac-21-31‚HCl, which were recrystallized.…”

“…Most of the required starting enones have been previously described: rac - 13a , − rac - 13b , d , g , i , and rac - 13c . Enones rac - 13e , f were prepared following a procedure previously developed by our group, based on the silica gel-promoted fragmentation of the mesylates 12 derived from the corresponding 3-alkyl-2-oxa-1-adamantanols 11 .…”

Adamantanes and related compounds. VIII. Behavior of endo-7-aminomethylbicyclo[3.3.1]nonan-3-one under reducing conditions

“…Reductions wherein lithium aluminum hydride has been used have given conflicting results. [7][8] We have found that a three-step procedure involving two reduction-dehydration sequences using sodium borohydride in methanol or 2-propanol converts many anthraquinones (1) to anthracenes (5) in a straightforward fashion, via the successive formation of 9,10-dihydroxy-9.10-dihydro intermediates, enthrones, and 9-hydroxy-9.10-dihydro intermediates. The steps are schematically represented wherein X represents one or more substituents on either or both end rings.…”

Synthesis of 2-Oxaadamantane Derivatives

“…There are two strategies for the construction of the 2-oxaadamantane system, the first of which is based on transannular cyclizations of bicyclo[3.3.1]nonane deriva­tives [ 13 ]. A number of 2-oxaadamantane deriv­atives were synthesized by cyclization of bicyclo­[3.3.1]­non-2-ene derivatives with an endo -oriented substituent at the 7-position [ 14 – 21 ]. Another method of synthesis of 2-oxaadamantane derivatives involves cyclization with participation of exocyclic bonds.…”