Potentiometric study of acid-base equilibria of 3,5-disubstituted 1,2,4,5-oxadiazaboroles in nonaqueous media

Article abstract of DOI:10.1021/je0604683

The protonation constants of the amino nitrogens of some substituted 1,2,4,5-oxadiazaboroles have been determined in acetic acid by means of potentiometric titration with perchloric acid. pK_a values of the title compounds were interpreted on the basis of structural effects due to the substituents and the main skeleton by plotting p_BH⁺ value versus Hammett constants. Good correlations between PK_BH⁺, σ constants, and δ_C=N and δ_NH values were also obtained.

Full text of DOI:10.1021/je0604683

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18
J. Chem. Eng. Data 2007, 52, 718-720
Potentiometric Study of Acid-Base Equilibria of 3,5-Disubstituted
,2,4,5-Oxadiazaboroles in Nonaqueous Media
1
Ya s¸ ar D u1 r u1 st,* Nedime D u1 r u1 st, and Muharrem Akcan
Department of Chemistry, Abant I˙ zzet Baysal University, TR-14280 Bolu, Turkey
The protonation constants of the amino nitrogens of some substituted 1,2,4,5-oxadiazaboroles have been determined
in acetic acid by means of potentiometric titration with perchloric acid. pKa values of the title compounds were
+
interpreted on the basis of structural effects due to the substituents and the main skeleton by plotting pKBH value
+
versus Hammett constants. Good correlations between pKBH , σ constants, and δCdN and δNH values were also
obtained.
Introduction
Scheme 1. Structures of 1,2,4,5-Oxadiazaboroles
Potentiometric titration in nonaqueous media is a standard
method for the determination of the basicity and acidity of
various compounds, particularly in organic and pharmaceutical
analyses. The reason for using nonaqueous solvents is that many
organic compounds of pharmaceutical importance do not
dissolve in water. Furthermore, since water is amphoteric, only
a limited range of acid and base strengths can be determined in
this solvent.1
,2
Amidoximes are versatile precursors of many heterocyclic
compounds of pharmaceutical importance.3,4 On the other hand,
aryl boronic acids and their esters are highly popular as synthetic
intermediates in organic synthesis with their ease of conversion
to other functional groups (such as phenols and aryl halides)
with a well-known reaction.5 To the best of our knowledge,
a literature survey of oxadiazaboroles from amidoxime and
phenyl boronic acid reveals that only a limited number of reports
were given in 1960s and 1970s at which no spectral data were
supplied for those heterocycles.9
-8
Potentiometric Titrations. The potentiometric titrations were
performed in a 50 mL glass vessel equipped with a combined
pH electrode (Ingold), argon inlet and outlet tubes, a magnetic
stirrer, and a titrant inlet. Titrant additions were carried out by
means of a microburet with 0.01 mL graduations. The electrode
was modified using saturated KCl solution in anhydrous
methanol instead of aqueous KCl solution. A Thermo Orion
model 720 A Plus ionmeter was used to measure the cell EMF.
Perchloric acid solution diluted with glacial acetic acid was
used as titrant. The concentration of the oxadiazaboroles was
,10
As a continuing part of our studies11,12 on the acid-base
equilibria of the amidoximes and related compounds, in this
work we report the potentiometric determination of basicity
(protonation) constants of the novel 3,5-disubstituted 1,2,4,5-
oxadiazaboroles (Scheme 1) in acetic acid.
Experimental Section
-
3
maintained as 10 M in glacial acetic acid. All measurements
were conducted with constant stirring of 30 mL of sample
solution (magnetic stirbar) at 25.0 ( 0.1 °C. Titration curves
were constructed by plotting the potential change (from the
initial baseline value) versus the concentration of added titrant
solution. The end points of titration were calculated by the
Kolthoff method. The half-neutralization potentials (HNP) were
determined by using these sigmoidal curves. In calculations of
the pKa values, ∆HNP (mV) values from the sigmoidal curves
of the samples and the corresponding ∆EMF values in calibra-
tion plot were used; 59 mV was taken as corresponding to one
pH unit.
Phenylboronic acid was purchased from Aldrich. Aldehydes
and nitriles were purchased from Merck and Fluka. Amidoximes
and oxadiazaboroles were prepared according to literature
procedures described previously.1
0,13-19 1
13
H and C NMR spectra
were recorded on Bruker and Varian spectrometers (300 and
00 MHz). IR spectra were recorded on a Jasco 430 FT/IR
4
instrument (KBr pellet). Mass spectra were measured on a
Agilent GC 6890N gas chromatograph with mass detector MS
5
975. Melting points were determined on a Meltemp apparatus
and uncorrected. TLC was done using precoated plates with
fluorescent indicator (Merck 5735). The stain solutions of
permanganate, p-anisaldehyde, and iodine were used for visu-
alization of the TLC spots.
Results and Discussion
pKBH+ values of nonaromatic heterocyclic compounds bearing
oxygen, nitrogen, and boron in same ring, namely, oxadiaza-
*
2
Corresponding author. E-mail: yasardurust@ibu.edu.tr. Tel: +90-374-
541243. Fax: +90-374-2534642.
1
0.1021/je0604683 CCC: $37.00 © 2007 American Chemical Society
Published on Web 03/16/2007

Journal of Chemical and Engineering Data, Vol. 52, No. 3, 2007 719
Table 1. Basicity (protonation) Constants, δCdN (ppm), and δNH
ppm) Values of 3,5-Disubstituted 1,2,4,5-Oxadiazaboroles
(
pKBH+
in acetic
acid)
δCdN (ppm)
δNH (ppm)
(
(in DMSO-d6 (in DMSO-d6
entry
R
+ CDCl3)
+ CDCl3)
2
2
2
2
2
2
2
2
2
2
a
b
c
d
e
f
g
h
i
methyl
phenyl
p-tolyl
3.58 ( 0.04
3.29 ( 0.05
3.40 ( 0.05
158.28
159.88
160.00
159.60
159.11
159.14
159.30
160.03
158.41
159.98
8.92
9.57
9.47
9.25
9.81
9.88
9.81
9.35
10.09
9.67
p-methoxyphenyl 3.49 ( 0.07
p-chlorophenyl
p-bromophenyl
p-iodophenyl
2-aminophenyl
p-nitrophenyl
p-N,N-dimethyl-
aminophenyl
2-pyridyl
3.18 ( 0.12
3.19 ( 0.09
3.11 ( 0.04
a
2.89 ( 0.05
3.63 ( 0.01
j
2
2
2
2
k
l
m
n
2.93 ( 0.02
159.55
157.77
158.30
156.04
8.66
10.19
10.04
9.67
a
3-pyridyl
4-pyridyl
2-thienyl
3.48 ( 0.02
3.11 ( 0.07
Figure 2. Plot of σp constants20 vs pKBH+ values.
a
Due to the initial protonation of substituents (-NH2 and pyridyl
nitrogen), a good sigmoid curve leading to the determination of the end
point could not be obtained.
Figure 3. Plot of pKBH+ versus δCdN (ppm).
Br, I, and NO2, which have higher Hammett σ constants with
+
lower pKBH values) appeared on the other end of the graph.
These results are in good accordance with the expected behavior
of these groups based on the basicity of amino nitrogen atom
of oxadiazaborole ring (atom no. 4 in oxadiazaborole ring
numbering). In this regard, when there are ERG groups present
on the phenyl ring, there will be an increase in the electron
density that may result in resonance delocalization of the lone
pairs on the N and O atoms through the aromatic ring and, thus,
a higher basicity of these compounds. In the case of EWG
Figure 1. Representative titration curve of mL of titrant vs ∆mV.
Scheme 2
+
groups on the phenyl ring, a reverse effect on pKBH values
are observed due to the substantial decrease in the electron
density of the amino nitrogen atom of the oxadiazaborole ring
through resonance delocalization of the nitrogen lone pair of
the ring, that is, basicity of oxadiazaboroles with electron-
withdrawing groups on the phenyl ring is decreased depending
on the nature of these groups.
boroles (Scheme 1), were determined potentiometrically in the
medium of glacial acetic acid. Results are given in Table 1,
and a typical titration curve is shown in Figure 1.
On the other hand, a correlation between 13C NMR chemical
shifts of imino carbons (atom no. 3) of oxadiazaboroles and
Protonation of the oxadiazaborole heterocycle by an acid will
3
take place on the 4-amino nitrogen that is sp -hybridized due
+
+
to the lone pair of electrons on this nitrogen being more available
pKBH values were accomplished, that is, the higher the pKBH
2
than the imino one, which is sp -hybridized. (Scheme 2). X-ray
values, the higher carbon chemical shifts (Figure 3).
data of some of the compounds also show the corresponding
bond length and bond angle.
Also, a linear correlation was found between Hammett σ
13
constants and C NMR chemical shifts of imino carbons (Figure
4). In addition, the chemical shift positions of NH protons of
the oxadiazaborole ring and Hammett σ constants are correlated
(Figure 5). The graph accounts for the higher NH chemical shifts
while a strongly electron-withdrawing substituent like NO2 on
the phenyl ring is present at the 3-position of the heterocycle.
A lower δ value (NH chemical shift) was observed when an
pKBH+ values obtained for the title compounds were cor-
related with Hammett σp constants. In Figure 2, it is clearly
seen that electron-releasing substituents (ERG) (i.e., dimethyl
amino and methoxy, which have lower Hammett σ constants
+
with higher pKBH values) appeared on the one end of the line
and that electron-withdrawing substituents (i.e., halogens, Cl,

7
20 Journal of Chemical and Engineering Data, Vol. 52, No. 3, 2007
Supporting Information Available:
Experimental procedures, physical, and spectral data for the
compounds 2a-n and crystallographic data for 2n. This information
is available free of charge via the Internet at http: //pubs.acs.org.
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+
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8
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(
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(
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Received for review October 22, 2006. Accepted February 18, 2007.
Acknowledgment
Abant I˙ zzet Baysal University Research Fund (BAP Grant
2006.03.03.249) is gratefully acknowledged for financial support.
The authors thank Dr. F. R. Fronczek (Louisiana State University,
USA) for X-ray diffraction data.
JE0604683