Reaction of dibromoadamantanes with glycols in the presence of sodium glycolate

Abstract

1,3-Dibromoadamantanes reacted with glycols in the presence of sodium glycolate to give novel unsaturated bicyclo[3.3.1]nonane derivatives and 1,3-disubstituted adamantanes. X = Cl, Br, MeO, MeS, H 2 N, MeNH, Me 2 N.Fragmentation of some 1,3-disubstituted adamantanes through intermediate formation of stabilized 3-substituted 7-methylidenebicyclo[3.3.1]non-3-yl cations was reported in [1][2][3][4][5][6][7]; in the presence of water the latter were converted into 7-methylidenebicyclo-[3.3.1]non-3-one (Scheme 1). Presumably, in strongly basic medium such carbenium ions can be stabilized via elimination of proton with formation of double C=C bond.We previously found [8] that 1,3-dibromoadamantane (I) in ethylene glycol at 200°C in the presence of a strong base is converted into a mixture of 2-(7-methylidenebicyclo[3.3.1]non-2-en-3-yloxy)ethanol (II) and 7-methylidenespiro[bicyclo[3.3.1]nonane-3,2′-[1,3]dioxolane] (III). More detailed analysis of the product mixture allowed us to reveal 10-12% of 2,2′-(adamantane-1,3-diybisoxy)diethanol (IV). 1,3-Dibromo-5,7-dimethyladamantane (VI) reacted in a similar way (Scheme 2).The products were isolated from the reaction mixture by selective extraction and subsequent vacuum distillation or recrystallization from appropriate solvent.As might be expected [9], vinyl ether II upon distillation or heating to 100°C, as well as during chromatography on silica gel, is quantitatively converted into spiro dioxolane III. Protection of the hydroxy group by esterification made it possible to isolate by vacuum distillation 2-(7-methylidenebicyclo-[3.3.1]non-2-en-3-yloxy)ethyl acetate (Va); the corresponding p-nitrobenzoate Vb was isolated by fractional recrystallization from methanol. Compounds IVa and IXa were isolated and characterized as p-nitrobenzoates IVb and IXb (Scheme 2).The structure of the products obtained by reactions of 1,3-dibromoadamantanes I and VI with ethylene glycol suggests the following reaction mechanism. 1,3-Dibromoadamantane I or VI in polar medium gives rise to 3-bromoadamantan-1-yl cation which takes up ethylene glycol molecule to produce intermediate A. Heterolytic dissociation of the C-Br bond in A generates cation B which undergoes Grob fragmentation with formation of carbenium ion C. The latter can be stabilized according to two pathways. Intramolecular proton abstraction from the α-carbon

Different routes for the construction of biologically active diversely functionalized bicyclo[3.3.1]nonanes: an exploration of new perspectives for anticancer chemotherapeutics

“…189 The fragmentation reaction of 1,3-disubstitutedadamantanes to produce bicyclo[3.3.1]nonane derivatives has been well investigated in the last 50 years. [190][191][192][193][194][195][196] Toward this 197,198 Another simple and convenient synthesis of 1,3,7-trisubstituted bicyclo[3.3.1]nonanes from adamantane derivatives was described by Majerski's group. Their journey commenced from 1-hydroxyadamantane-4-one (447), which, upon sequential ring expansion and oxidation, yielded the ring opening precursor 448, an adamantane-dione derivative, which on treatment with HIO 4 yielded the bicyclic 1,3-dicarboxylic acid 449 in 36% yield (Scheme 102).…”

“…It is believed that an intermediate adamantyl carbocation ( 444 ), formed by the bromide elimination from 443 , yielded the differently substituted bicycles in a stepwise manner. 197,198…”

“…[190][191][192][193][194][195][196] Toward this 444), formed by the bromide elimination from 443, yielded the differently substituted bicycles in a stepwise manner. 197,198 Another simple and convenient synthesis of 1,3,7-trisubstituted bicyclo[3.3.1]nonanes from adamantane derivatives was described by Majerski's group. Their journey commenced from 1-hydroxyadamantane-4-one (447), which, upon sequential ring expansion and oxidation, yielded the ring opening precursor 448, an adamantane-dione derivative, which on treatment with HIO 4 yielded the bicyclic 1,3-dicarboxylic acid 449 in 36% yield (Scheme 102).…”