Cyclodextrins as enzyme models in nitrosation and in acid-base- catalyzed reactions of alkyl nitrites

Article abstract of DOI:10.1021/ja9827696

The widely studied cyclodextrin-mediated reactions of esters but not those of alkyl nitrites, together with the marked differences between the chemistry of esters and alkyl nitrites, prompted us to investigate the influence of β-cyclodextrin (β-CD) on the reactions of alkyl nitrites. Due to the particular characteristics of alkyl nitrite reactions, the system β- cyclodextrin-alkyl nitrites allows us to explore cyclodextrin's behavior under several experimental conditions, contrary to the case of esters. Therefore, general acid-base-catalyzed hydrolysis and nitrosation of amines by alkyl nitrites are studied. Alkyl nitrites of a particular structure have been chosen to clearly evidence the mimicry of enzyme catalysis by β-CD. Addition of β-CD strongly inhibits the acid hydrolysis of alkyl nitrites (a very fast reaction in water), except in the case of ethoxyethyl nitrite, where no effect is detected. The retardation of the reaction is attributed to a separation of the reagents: β-CD and alkyl nitrites form host-guest 1:1 inclusion complexes, but simple cations, such as H₃O⁺ in the present case, did not prove to include into the β-CD cavity. In fact, at constant β-CD concentrations, addition of dodecyltrimethylammonium bromide monomers (DTABr), which strongly compete with alkyl nitrites for the hydrophobic β- CD cavity and, thus, expel the alkyl nitrites, catalyzes the reaction. On the contrary, in alkaline medium, when a secondary hydroxy group of β-CD is ionized, addition of β-CD to the reaction medium strongly catalyzes the basic hydrolysis of alkyl nitrites (an extremely slow reaction in water). The degree of catalysis depends on the alkyl nitrite structure, varying from a factor higher than 100 in the case of 3-phenyl-1-propyl nitrite, to 0 (no reaction is observed) in the case of 2-phenyl-2-propyl nitrite. The effective molarities calculated for the catalysis evidence a base-catalyzed mechanism for the reaction. The strong catalysis observed with 1-phenyl-1-propyl nitrite upon the addition of DTABr is indicative of an example of allosteric activation. Finally, the nitrosation of pyrrolidine, piperidine, and cyclohexylamine by ethoxyethyl nitrite is slightly catalyzed by the presence of β-cyclodextrin. The degree of the observed catalysis depends on both the amine concentration and the structure.