Stereochemistry of beta-deuterium isotope effects on amine basicity.
Secondary beta-deuterium isotope effects on amine basicities are measured using a remarkably precise NMR titration method. Deuteration is found to increase the basicity of methylamine, dimethylamine, benzylamine, N,N-dimethylaniline, 2-methyl-2-azanorbornane, and pyrrolizidine. The increase in dimethylamine arises entirely from enthalpy, contrary to a previous report. The method permits a determination of intramolecular isotope effects in 1-benzyl-4-methylpiperidine and 2-benzyl-2-azanorbornane. It is found that deuteration has a larger isotope effect when either antiperiplanar or synperiplanar to a lone pair, but the synperiplanar effect is smaller, as confirmed by computations. The isotope effect is attributed to a lowered zero-point energy of a C-H bond adjacent to an amine nitrogen, arising from delocalization of either a syn or an anti lone pair, and with no detectable angle-independent inductive effect.
Department of Chemistry 0358, University of California, San Diego, La Jolla, California 92093-0358, USA. cperrin@ucsd.edu
Charles L
CL
Perrin
Brian K
BK
Ohta
Joshua
J
Kuperman
Jordan
J
Liberman
Máté
M
Erdélyi
D000588:Amines / Q000737:chemistry*; D000814:Aniline Compounds / Q000737:chemistry; D001596:Benzylamines / Q000737:chemistry; D003903:Deuterium / Q000737:chemistry*; D004123:Dimethylamines / Q000737:chemistry; D007553:Isotope Labeling / Q000379:methods; D009682:Magnetic Resonance Spectroscopy; D008744:Methylamines / Q000737:chemistry; D009584:Nitrogen / Q000737:chemistry; D009636:Norbornanes / Q000737:chemistry; D011763:Pyrrolizidine Alkaloids / Q000737:chemistry; D013237:Stereoisomerism; D013696:Temperature
D000588:Amines; D000814:Aniline Compounds; D001596:Benzylamines; D004123:Dimethylamines; D008744:Methylamines; D009636:Norbornanes; D011763:Pyrrolizidine Alkaloids; C015157:N,N-dimethylaniline; C030796:benzylamine; D003903:Deuterium; C027451:methylamine; D009584:Nitrogen