A R T I C L E S
Perrin et al.
pensation of force constants, but it too would be consistent with
systematic error from an impurity. Besides, temperature inde-
pendence would require that the IE lie in the entropy. For
trimethylamine-d9 ∆pKa is 0.185,10 large enough to be beyond
experimental error, but this could be due to steric repulsions,
which flatten trimethylamine-h9, with its longer C-H bonds,
This method is capable of exquisite precision, because it is
based only on chemical-shift measurements, not on pH or
volume or molarity as in the usual pH titrations. The method is
comparative. If there is no difference in basicities, there is no
lag of one chemical shift behind the other. Therefore minute
imbalances of basicities can be detected. Moreover, because the
titration is performed on a mixture of the two bases, under
conditions guaranteed identical for both, it avoids systematic
error due to impurities. Further advantages are that it is
applicable to a mixture of closely related substances, without
the necessity of separating them, and that it can be applied in
any solvent, even those where a pH electrode would be
inoperative. Variants on this method have been developed for
1
1
owing to anharmonicity.
All of these cases differ from solvolyses in that there is no
rehybridization, neither of the carbon bearing the isotope nor
3
of the nitrogen, which remains nominally sp on deprotonation.
Besides, the increase of basicity is opposite to deuterium’s
reduced electron-donating power in solvolyses. The IE in
benzylamine was therefore attributed to an electrostatic interac-
tion between the positive charge on the protonated nitrogen and
the dipole moment of the C-H or C-D bond.12 Because dipole
1
9
13
17
measuring IEs, using F and C NMR, but without the
advantage of data analysis by linear least squares.
IEs are now measured for deuterated methylamine (1-d0,1,2,3),
dimethylamine (2-d3), benzylamine (3-d), N,N-dimethylaniline
moment is the product of charge separation and bond length,
and because the C-H bond is longer than C-D, owing to
anharmonicity, deuterium could show an electron-donating
capability. Such an inductive effect, arising from monopole-
dipole interaction, is consistent with the Born-Oppenheimer
approximation. It seems to have been accepted as the source of
(4-d3), 2-methyl-2-azabicyclo[2.2.1]heptane (5-d2), and pyr-
rolizidine (6-d). Mixing any of these with the corresponding
1
unlabeled material produces a H NMR spectrum that shows
1
8
resolvable isotope shifts from the different isotopologues
(isotopic homologues). The relevant reporter nuclei are depicted
in boldface in the molecular structures. The acidity constant
ratios for the isotopomers (isotopic stereoisomers) of 1-benzyl-
1
3
these IEs, even though the dipole moments involved are
exceedingly small.
This inductive contribution can be estimated (if the dipole-
dipole interaction between the lone pair and the bond is ignored
relative to monopole-dipole). Anharmonicity leads to a dCH -
dCD of 0.34 pm. From infrared intensities of methane, the
derivative of dipole moment with respect to C-H distance is
4-methylpiperidine-d3 (7-d3) and 2-benzyl-2-azabicyclo[2.2.1]-
heptane (8-d) are also determined. Some of these results have
1
9
been presented in a brief report.
0
0
.016e.14 The field effect on pK due to a dipole moment of
.35D, as in propene, can be estimated as 0.95, the ∆pK between
allylamine and methylamine. These combine to a ∆pK on
deuteration of 0.0007, which is much smaller than the claimed
IE.
Because we needed to be certain about such IEs before
embarking on a study to assess the symmetry of NHN hydrogen
15
bonds in tetramethylnaphthalenediamines, we have reinves-
tigated them. A new NMR titration method makes it possible
Experimental Section
1
6
to measure relative basicities with great precision. The
procedure involves successive additions of small aliquots of acid
to a mixture of bases. Acid will preferentially protonate the one
that is more basic. Its chemical shift will then move ahead of
that of the less basic one, which lags behind. Alternatively, it
may be more convenient to add aliquots of base to a mixture
of acids. Regardless, the acidity constants Ka and chemical shifts
NMR Spectroscopy. H and 13C NMR spectra were recorded on a
1
Varian Mercury 400 or Unity 500 spectrometer. Chemical shifts in
aqueous solutions are relative to tert-butyl alcohol (δ 1.23) or dioxan
1
(δ 3.75) as internal standard. The H NMR signals of deuterated 1-6
were easily distinguished from those of undeuterated by using samples
of known stoichiometry.
Syntheses. Benzylamine, N,N-dimethylaniline, dimethylamine‚HCl,
+
0
δ can be related through eq 1, where δ or δ is for the
protonated or deprotonated form, as measured at the beginning
or end of the titration. Therefore a plot of the quantity on the
dimethyl-1,1,1-d -amine‚HCl, and other reagents were commercially
3
available and used without purification. Deuterated amines were
obtained by reduction of a suitable precursor (trimethylsilyl isothio-
cyanate, benzaldehyde oxime, N-methyl-N-phenylcarbamic acid methyl
ester, N-benzyl-3-methylglutarimide, ∆4 -dehydropyrrolizidinium per-
+
left versus (δ1 - δ1°)(δ2 - δ2) should be linear with zero
(8)
intercept and with a slope equal to the ratio of acidity constants.
chlorate, or 2-benzyl-2-azabicyclo[2.2.1]heptan-3-one) with LiAlD
4
or
a LiAlD -LiAlH mixture. The ratio of LiAlD to LiAlH was adjusted
empirically so as to produce H NMR spectra in which the reporter
peaks for all isotopologues are nearly equal in height, so that small
4
4
4
4
δ1+ - δ )(δ - δ °) ) (K /K )(δ - δ °)(δ - δ2) (1)
1
2
+
(
1
1
2
2
a
a
1
1
2
(
10) Northcott, D.; Robertson, R. E. J. Phys. Chem. 1969, 73, 1559.
11) Anet, F. A. L.; Basus, V. J.; Hewett, A. P. W.; Saunders, M. J. Am. Chem.
Soc. 1980, 102, 3945.
(
(17) Forsyth, D. A.; Yang, J.-R. J. Am. Chem. Soc. 1986, 108, 2157. Pehk, T.;
Kiirend, E.; Lippmaa, E.; Ragnarsson, U.; Grehn, L. J. Chem. Soc., Perkin
Trans. 2 1997, 445.
(18) Batiz-Hernandez, H.; Bernheim, R. A. Prog. Nucl. Magn. Reson. Spectrosc.
1967, 3, 63. Jameson, C. J.; Osten, H. J. Annu. Rep. NMR Spectrosc. 1986,
17, 1. Hansen, P. E. Prog. Nucl. Magn. Reson. Spectrosc. 1988, 20, 207.
Dziembowska, T.; Hansen, P. E.; Rozwadowski, Z. Prog. Nucl. Magn.
Reson. Spectrosc. 2004, 45, 1.
(19) Perrin, C. L.; Ohta, B. K.; Kuperman, J. J. Am. Chem. Soc. 2003, 125,
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(
(
(
12) Halevi, E. A. Prog. Phys. Org. Chem. 1963, 1, 109.
13) Toyota, S.; Oki, M. Bull. Chem. Soc. Jpn. 1992, 65, 2215.
14) Oliveira, A. E.; Guadagnini, P. H.; Cust o´ dio, R.; Bruns, R. E. J. Phys.
Chem. A 1998, 102, 4615.
(
15) Perrin, C. L.; Ohta, B. K. J. Am. Chem. Soc. 2001, 123, 6520. Perrin, C.
L.; Ohta, B. K. J. Mol. Struct. 2003, 644, 1.
(
16) Perrin, C. L.; Fabian, M. A.; Armstrong, K. B. J. Org. Chem. 1994, 59,
5
246. Perrin, C. L.; Fabian, M. A. Anal. Chem. 1996, 68, 2127.
9642 J. AM. CHEM. SOC.
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VOL. 127, NO. 26, 2005