ABSTRACT
Multinuclear NMR studies of five-membered-ring amine chelated aryllithium reagents 2-lithio-N,N-dimethylbenzylamine (1), the diethylamine and diisopropylamino analogues (2, 3), and the o-methoxy analogue (4), isotopically enriched in (6)Li and (15)N, have provided a detailed picture of the solution structures in ethereal solvents (usually in mixtures of THF and dimethyl ether, ether, and 2,5-dimethyltetrahydrofuran). The effect of cosolvents such as TMEDA, PMDTA, and HMPA has also been determined. All compounds are strongly chelated, and the chelation is not disrupted by these cosolvents. Reagents 1, 2, and 3 are dimeric in solvents containing a large fraction of THF. Below -120 degrees C, three chelation isomers of the dimers are detectable by NMR spectroscopy: one (A) with both nitrogens coordinated to one lithium of the dimer, and two (B and C) in which each lithium bears one chelating group. Dynamic NMR studies have provided rates and activation energies for the interconversion of the 1-A, 1-B, and 1-C isomers. They interconvert either by simple ring rotation, which interconverts B and C, or by amine decoordination (probably associative, DeltaG(++)(-93) = 8.5 kcal/mol), which can interconvert all of the isomers. The dimers of 1 are thermodynamically more stable than those of model systems such as phenyllithium, o-tolyllithium, or 2-isoamylphenyllithium (5, DeltaDeltaG > or = 3.3 kcal/mol). They are not detectably deaggregated by TMEDA or PMDTA, although HMPA causes partial deaggregation. The dimers are also more robust kinetically with rates of interaggregate exchange, measured by DNMR line shape analysis of the C-Li signal, orders of magnitude smaller than those of models (DeltaDeltaG(++) > or = 4.4 kcal/mol). Similarly, the mixed dimer of 1 and phenyllithium, 13, is kinetically more stable than the phenyllithium dimer by >2.2 kcal/mol. X-ray crystal structures of the TMEDA solvate of 1-A and the THF solvate of 3-B showed them to be dimeric and chelated in the solid state as well. Compound 4, which has a methoxy group ortho to the C-Li group, differs from the others in being only partially dimeric in THF, presumably for steric reasons. This compound is fully deaggregated by 1 equiv of HMPA. Excess HMPA leads to the formation of ca. 15% of a triple ion (4-T) in which both nitrogens appear to be chelated to the central lithium.
ABSTRACT
[figure: see text] Chelation and aggregation in phenyllithium reagents with potential 5-, 6-, and 7-ring chelating ether and amine ortho substituents have been examined utilizing variable-temperature 6Li and 13C NMR spectroscopy, 6Li and 15N isotope labeling, and the effects of solvent additives. Both ether and amine form strong 5-ring chelates; 6-ring ether chelates compete well with THF, but 6-ring amine chelates barely do, and 7-ring amine chelates do not. o-Methoxymethylphenyllithium (4) forms an open dimer (9) and a pentacoordinate monomer with PMDTA (10).
ABSTRACT
Human heart rate, controlled by complex feedback mechanisms, is a vital index of systematic circulation. However, it has been shown that beat-to-beat values of heart rate fluctuate continually over a wide range of time scales. Herein we use the relative dispersion, the ratio of the standard deviation to the mean, to show, by systematically aggregating the data, that the correlation in the beat-to-beat cardiac time series is a modulated inverse power law. This scaling property indicates the existence of long-time memory in the underlying cardiac control process and supports the conclusion that heart rate variability is a temporal fractal. We argue that the cardiac control system has allometric properties that enable it to respond to a dynamical environment through scaling.
