Dealkylation s. a. Elimination

Dealcoholation 16, 945 Dealkylation (s. a. Elimination of alkyl groups. Monodealkylation)... 

Dealkylation (s. a. Elimination of alkyl groups. Monodealkylation, Replacement of alkyl groups by hydrogen) G-Dealkylation, quinoline ring with — 12, 948 N-Dealkylation (s. a. N-De-methylation) 14, 50, 54, 769 0-Dealkylation (s. a. Ethers, cleavage)... 

In mammalian liver microsomes, cytochrome P-450 is not specific and catalyzes a wide variety of oxidative transformations, such as (i) aliphatic C—H hydroxylation occurring at the most nucleophilic C—H bonds (tertiary > secondary > primary) (ii) aromatic hydroxylation at the most nucleophilic positions with a characteristic intramolecular migration and retention of substituents of the aromatic ring, called an NIH shift,74 which indicates the intermediate formation of arene oxides (iii) epoxidation of alkenes and (iv) dealkylation (O, N, S) or oxidation (N, S) of heteroatoms. In mammalian liver these processes are of considerable importance in the elimination of xenobiotics and the metabolism of drugs, and also in the transformation of innocuous molecules into toxic or carcinogenic substances.75 77... 

A peculiai- case of phosphoryl radical addition to difluoroalkenes involves the reaction of trialkyl phosphites with l-bromo-2-iodo-l,l,2,2-tetfafluoroethane under ultraviolet irradiation (254 nm). Surprisingly, the corresponding 2-iodo-l,l,2,2-tetrafluoroethylphosphonates are formed in 42 8% yields with no detectable amount of the bromo derivative (Scheme 3.39). The proposed mechanism involves a halide-induced dealkylation of the trialkyl phosphite radical cation followed by addition of the product phosphoryl radical to tetrafluoroethene (generated by halide anion elimination) and iodide radical abstraction from the starting haloalkane. s... 

Ionic liquid stability is known to be a function of temperature (for details see Section 3.1) but the presence of nucleophiles/bases and the water content also have to be considered. There is no doubt that, under the conditions of a catalytic reaction, temperature stability issues are more complicated than imder the conditions of a TGA experiment. The presence of the catalyst complex, the reactants and impurities in the system may well influence the thermal stability of the ionic liquid. Basic and nucleophilic counter-ions, reactants and metal complexes may not only lead to deprotonation of 1,3-dialkylimidazolium ions (to form carbene moieties that will undergo further consecutive reactions) but will also promote thermal dealkylation of the ionic liquid s cation. If basic reaction conditions are required for the catalysis only tetraalkylphosphonium ions can be recommended as the ionic liquid s cation at this point in time. Tetraalkylphosphonium cations have been recently shown to display reasonabe stability, even under strongly basic conditions [290]. In contrast, all nitrogen-based cations suffer to some extent from either carbene formation, Hofmann elimination or rapid dealkylation (with alkyl transfer onto the nucleophilic anion). 

But there are also shifts in paradigms that have clearly opened the field and will certainly inspire a lot of great science in the future. For example, ionic liquids have been perceived in the past to be notoriously unstable towards strong bases due to carbene formation, Hofmann-elimination or dealkylation [44]. Recent work by Clyburne s group [45] and QUILL/Belfast [46] has impressively demonstrated, however, that some ionic liquid structures can indeed be quite base stable and these ionic liquids have been successfully applied in organic reactions in contact with strongly basic reagents. 

Metoprolol is another beta-blocker that is predominantly eliminated by hepatic metabolism [38]. In humans, metoprolol is eliminated by several oxidation pathways, including benzylic hydroxylation (a-hydroxylation), which results in an active metabolite and accounts for 10% of the dose [39]. This pathway is stereoselective for S(—)-metoprolol. The major metabolic pathway, however, is O-demethylation and further oxidation to a carboxylic acid metabolite that accounts for 65% of the dose [38]. O-demethylation favors R(- -)-metoprolol [39] and facilitates the stereoselectivity observed in the plasma concentrations of metoprolol. A third metabolic pathway (N-dealkylation) accounts for < 10% of the dose in humans [39]. 

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