Heterocycles methylamine functionalization

In a more recent study, Westman and Lundin have described solid-phase syntheses of aminopropenones and aminopropenoates en route to heterocycles [32], Two different three-step methods for the preparation of these heterocycles were developed. The first method involved the formation of the respective ester from N-pro-tected glycine derivatives and Merrifield resin (Scheme 7.12 a), while the second method involved the use of aqueous methylamine solution for functionalization of the solid support (Scheme 7.12 b). The desired heterocycles were obtained by treatment of the generated polymer-bound benzylamine with the requisite acetophenones under similar conditions to those shown in Scheme 7.12 a, utilizing 5 equivalents of N,N-dimethylformamide diethyl acetal (DMFDEA) as reagent. The final... 

Ammonium salts with two different alkyl chains were prepared directly via subsequent alkylations of dimethylamine with primary bromides and crystallization. Commercial hexadecyl-methylamine can be conveniently applied in the same way in order to convey functionality to cationic synkinons. A recent example describes subsequent alkylations with a small functional and a long-chain primary bromide (Scheme 2.4). A-acylated / -phenylenediamine was also alkylated at the second nitrogen atom which had two different alkyl chains, with or without extra functionality . After deacylation, this head group can be diazotized or coupled oxidatively with various heterocycles in water (Scheme 2.4). Photoactive and coloured membrane surfaces are thus obtained. Phenylene-diamine, pyridine and in particular A-methyl-4,4-bipyridinium chloride are relatively weak nucleophiles. Substitution of bromides is slow and the more reactive iodides can rarely be obtained commercially, but the selection of nitromethanes as solvent for bromide substitution is of great help as well as the addition of sodium iodide to enforce a Finkelstein reaction or a combination of both. 

With sp C-H bonds adjacent to heteroatoms such as nitrogen, an sp -sp C-C bond can also be formed by CDC reaction. In 2009, the group of Kami described the direct functionalization of methylamines (2.5 equiv.) with various heterocycles (1 equiv.) in the presence of FeClz 4H2O (10 mol%), with pyridine-iV-oxide (2 equiv.) as the oxidant and two additives [KI (0.2 equiv.) and 2,2 -Bipyridine (bipy) (O.l equiv.)] at 130 °C for 24 h (Scheme 4.19). ... 

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