Dealkylation, cyclic ethers

Reductive C-N bond cleavage has been demonstrated in more complex systems using ethyl chloroformate as a solvent. Chlorination of corticosteroid cyclic ethers has been observed. Tertiary aliphatic and alicyclic amines can be dealkylated. Phenyl chloroformate, however, is usually regarded as the reagent of choice. In summary, deamination, demethylation, debenzylation, and deal-lylation of tertiary amines can all occur on treatment with ethyl chloroformate but the regioselectivities of these reactions are difficult to predict. ... 

The synthesis of macropolycyclic cryptands generally involves stepwise, straightforward pathways (18, 20, 33) based on the successive construction of systems of increasing cyclic order macrocyclic, macrobicyclic, and so on. Newkome has recently reported a satisfactory quaternization-dealkylation procedure, facilitating the synthesis of 8 (34). Unlike the synthetic approaches to simple crown ethers (10,... 

Methoxyallyl cation (5a Y = OMe), derived from 2-methoxyallyl bromide (4a X = Br, Y = OMe) and silver trifluoroacetate in the presence of sodium carbonate, reacts with benzene, toluene, p-xylene or mesitylene. 2-Ethoxyallyl alcohol (4c X = OH, Y = OEt) in the presence of trifluoroacetic anhydride generates the 2-ethoxyallyl cation (5c Y = OEt). 2-Ethoxyallyl alcohol (4c) is probably more advantageous than the corresponding 2-methoxyallylic species (4a Y = OMe) because dealkylation of the intermediary oxonium ion seems to be less facile, and the ethyl enol ether is more nucleophilic than the methyl enol ether. Treatment of cyclic a-chloroenamines (4f X = Cl, Y = morpholino) and (4g X = Cl,... 

Metabolites derived by loss of an alkyl or arylalkyl group from ethers [Eq. (4)], thioethers [Eq. (5)], amines [Eq. (6)], and amides [Eq. (7)] represent common biotransformation pathways (R, R" = H, alkyl or aryl). These processes involve oxidation on carbon adjacent to the heteroatom. The intermediates are generally unstable and readily decompose to the corresponding alcohol, thiol, amine, or amide and an aldehyde. Intermediates formed from amides [Eq. (7)] are more stable and may be detected as excreted metabolites. If a secondary carbon atom is adjacent to the heteroatom, then this portion of the molecule is released as a ketone. The heteroatom may also be located in a cyclic structure (e.g., morpholine, piperazine). Two processes have been adopted for amines, namely, N-dealkylation or deamination, that are essentially the same event. In general, which of the two terms applies depends on the... 

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