10.1021/ac960117z.s002
Charles L. Perrin
Charles L.
Perrin
Miles A. Fabian
Miles A.
Fabian
Multicomponent NMR Titration for Simultaneous
Measurement of Relative p<i>K</i><sub>a</sub>s
American Chemical Society
1996
1 H NMR titration experiment
ΔΔ
Relative p K
butylcyclohexanecarboxylic acid 2
tert
OD
H 1 chemical shifts
conjugate acids
Δ p K
NMR titration method
trans stereoisomer 1 t
13 C NMR
3 tt
Multicomponent NMR Titration
DMSO
1996-07-01 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Multicomponent_NMR_Titration_for_Simultaneous_Measurement_of_Relative_p_i_K_i_sub_a_sub_s/3583359
An NMR titration method has been developed to simultaneously measure the difference in acid dissociation
constants (Δp<i>K</i><sub>a</sub>) of two or more compounds with
high
precision and accuracy. The Δp<i>K</i><sub>a</sub> between
the conjugate
acids of the two stereoisomers of
4-<i>tert</i>-butylcyclohexylamine <b>1</b> was determined in a single <sup>1</sup>H NMR
titration
experiment. A mixture of the two stereoisomers was
titrated with DCl in a 3:1 (v/v) mixture of
CD<sub>3</sub>OD/D<sub>2</sub>O.
From the variations of the H1 chemical shifts the ratio
of
the acidity constants was determined. The trans
stereoisomer <b>1</b><sub>t</sub> was found to be the more basic by 0.121
±
0.002 p<i>K</i> unit. A repeat titration in
DMSO-<i>d</i><sub>6</sub> also found
<b>1</b><sub>t</sub> to be the more basic, by 0.217 ± 0.003
p<i>K</i> unit. The
Δp<i>K</i><sub>a</sub> between the two stereoisomers of
4-<i>tert</i>-butylcyclohexanecarboxylic acid <b>2</b> was determined in both of
these
solvents using <sup>1</sup>H and <sup>13</sup>C NMR.
Thermodynamic parameters ΔΔ<i>H</i>° and ΔΔ<i>S</i>° were evaluated
from the temperature dependence of Δp<i>K</i><sub>a</sub>. To further
demonstrate the
utility of this method, the Δp<i>K</i><sub>a</sub>s of the
conjugate acids of
the four stereoisomers of 2-decalylamine <b>3</b> were
determined in a single <sup>1</sup>H NMR titration experiment. The
cis,cis stereoisomer (<b>3</b><sub>cc</sub>) was found to be the most
basic, with
the cis,trans (<b>3</b><sub>ct</sub>), trans,cis
(<b>3</b><sub>tc</sub>), and trans,trans
(<b>3</b><sub>tt</sub>) less
basic by 0.012 ± 0.003, 0.037 ± 0.004, and 0.141 ±
0.005 p<i>K</i> unit, respectively. A second
four-component
titration was also performed with the two
4-<i>tert</i>-butylcyclohexylamines (<b>1</b>) and the two
<i>trans</i>-2-decalylamines
(<b>3</b><sub>tc</sub>, <b>3</b><sub>tt</sub>).