Product Protection

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Science  20 Feb 2009:
Vol. 323, Issue 5917, pp. 984
DOI: 10.1126/science.323.5917.984c

Chemical transformations often pose the dilemma that a desirable product may prove unstable under the reaction conditions. In certain cases, such intermediate products may be sufficiently volatile to be removed evaporatively from the reaction mixture as they are generated, but many compounds are not amenable to this mode of separation. A particularly insidious challenge arises in the partial alkylation of amines. Adding an alkyl group renders an amine more nucleophilic than before, and so more likely to attract yet another alkyl group; therefore, simply mixing equivalent amounts of amines and alkyl electrophiles tends to afford a mixture of unreacted and polyalkylated products. Yebeutchou and Dalcanale skirt the problem by adding molecular sequestering agents that selectively capture amines after their preliminary reaction step, thereby protecting them from further interaction with a methylating agent (iodomethane). The optimized protectors were tetra(arylphosphonate)-based cavitands that attracted monomethylated alkyl ammonium cations through ion-dipole forces, hydrogen bonding at the rim, and C-H-pi interactions deep in the cavity. In their presence, a range of alkyl and aryl primary amines could be selectively methylated in good yield. The authors verified preferential encapsulation of the secondary ammonium ions in solution using nuclear magnetic resonance spectroscopy. — JSY

J. Am. Chem. Soc. 131, 10.1021/ja809614y (2009).

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