Research Article
Received: 5 December 2011,
Revised: 16 March 2012,
Accepted: 5 April 2012,
Published online in Wiley Online Library: 11 May 2012
(wileyonlinelibrary.com) DOI: 10.1002/poc.2956
The basicity of substituted N,N-dimethylanilines
in solution and in the gas phase†
Ivari Kaljuranda*, Roman Lilleorga‡, Algis Murumaaa}, Masaaki Mishimab*,
Peeter Burka, Ivar Koppela, Ilmar A. Koppela** and Ivo Leitoa
Basicities of a number of ring-substituted N,N-dimethylanilines (DMA) and some related bases in water, acetonitrile,
and THF and in the gas phase have been experimentally determined. Gas-phase basicities of DMAs and related bases
were calculated at DFT B3LYP 6-311+G** and G3(MP2) levels. Structure–Basicity relationships in these four media
were discussed. By comparison of gas-phase basicity shifts induced by stepwise substitution, starting from ammonia
and ending at triphenylamine, it was observed that solvent effects of water and acetonitrile exceed the structural
effects on intrinsic basicity. It was shown that the influence of substituents in the phenyl ring on DMA basicity is
reduced by two to three times when going from the gas phase into the abovementioned condensed media. In the
gas phase, 4-NO, 4-NO2, 4-CN, 4-COMe, and 4-CHO substituted DMAs protonate on substituent, whereas in solvents,
only 4-NO-DMA probably protonates on substituent. The sensitivity of DMA basicity toward substitution in the
phenyl ring was compared with the related family of phenylphosphazene bases, and it was found that the substituent
effect is stronger in DMAs by 1.35 times in acetonitrile, 1.45 times in the gas phase, 2.0 times in THF, and 2.6 times in
water. Copyright © 2012 John Wiley & Sons, Ltd.
Supporting information may be found in the online version of this paper
Keywords: acetonitrile; basicity; B3LYP 6-311+G**; gas phase; G3(MP2); N,N-dimethylaniline; protonation site; THF; water
INTRODUCTION
J. Phys. Org. Chem. 2013, 26 171–181
* Correspondence to: I. Kaljurand; I. A. Koppel, Institute of Chemistry, University
of Tartu, Ravila 14 Str, 50411 Tartu, Estonia.
E-mail: [email protected]; [email protected]
** Correspondence to: M. Mishima, Institute for Materials Chemistry and
Engineering, Kyushu University, Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.
E-mail: [email protected]
†
‡
}
This article is published in Journal of Physical Organic Chemistry as a special
issue on 13th European Symposium on Organic Reactivity edited by Peeter
Burk (University of Tartu, Institute of Chemistry, 2 Jakobi St., Tartu, 51014,
Estonia) and Marie-Francoise Ruasse (Université Paris VII-CNRSItODYS, ITODYS,
15 rue Jean de Baïf, 75205 PARIS CEDEX 13, PARIS, 75205, France).
Current address: Estonian Veterinary and Food Laboratory, Kreutzwaldi 30,
51006, Tartu, Estonia
Current address: AS Balsnack IH, Ääsmäe, Harjumaa, 76402, Estonia
a I. Kaljurand, R. Lilleorg, P. Burk, I. Koppel, I. A. Koppel, I. Leito
Institute of Chemistry, University of Tartu, Ravila 14a Str, 50411, Tartu, Estonia
b M. Mishima
Institute for Materials Chemistry and Engineering, Kyushu University, Hakozaki,
Higashi-ku, Fukuoka 812-8581, Japan
Copyright © 2012 John Wiley & Sons, Ltd.
171
N,N-dimethylaniline (DMA) and its derivatives are used for
production of polymers, dyes, pharmaceuticals, agricultural
chemicals, etc.[1–5] Acid–Base properties of DMA and its derivatives have been of interest for several decades. The basicities of
several substituted DMAs have been determined in water[6–8]
and aqueous dimethylsulfoxide[9] and in the gas phase.[10–13]
The affinities of substituted DMAs toward trimethylsilyl cation
have been studied.[14] During the recent years, self-consistent
basicity scales of organic bases have been established in
THF[15–18] and acetonitrile (AN).[18–22] Both of these scales now
contain over 120 compounds (alkylamines, pyridines, anilines,
phosphazenes, phosphanes, guanidines, etc). These scales
include DMA, the parent compound of the family that is main
subject of the current study.
Despite these developments, the available experimental basicity data for substituted DMAs and related bases in the literature
are insufficient for making reliable conclusions about the effects
of molecular structure and medium on the basicities of DMAs
and related bases.
The information is somewhat more abundant for water and
the gas phase (Table 1). However, the experimental gas-phase
basicity values of a number of substituted DMAs were initially
determined by one of the authors (M.M.) by using the FT-ICRMS (Fourier transform ion cyclotron resonance mass spectrometry) method,[23] and these data[11] have been incorporated into
the NIST database[12,10] in a modified form without a reference
to their source and/or any experimental details. In this work,
the details of these experiments, experimental relative gasphase basicity values, and correct gas-phase basicity values of
compounds, which have not been previously published, are
presented. The experimental data are supplemented by calculated gas-phase basicities. The aim of this work was to supplement the available basicity data of DMAs and related bases in
different solvents and in the gas phase and to use these data
to explore the relations between the structure of these molecules and their basicity in different media. Protonation site of
DMAs and anilines have been topics of discussion.[24–31] This
work brings some experimental evidence of protonation site of
substituted DMAs in solution and in the gas phase.
I. KALJURAND ET AL.
Table 1. Basicity values from this work and literaturea
No
Base/Substitution
A
1
N,N-dimethylanilines
(DMA)
H
2
3
4
5
6
7
8
2-Me
2-NMe2
2-COOMe
2-Cl
2-Br
2-NO2
3-Me
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
3-C(CH3) = CH2
3-COOMe
3-COMe
3-CHO
3-MeO
3-F
3-Cl
3-Br
3-SCF3
3-CF3
3-SF5
3-CN
3-NO2
3-Tf
4-NMe2
4-NH2
4-C(CH3) = CH2
4-MeO
4-Me
4-COMe
4-F
30
31
32
33
34
35
36
37
38
39
4-CHO
4-Cl
4-Br
4-COOMe
4-SCF3
4-SCN
4-CF3
4-SO2Me
4-SF5
4-NO2
40 4-CN
41 4-NO
pKa (H2O)
pKa (AN)
pKip (THF)
pKa (THF)
GBexpb
5.13j, 5.10l,
5.15m, 5.07n,
5.21q
11.43p
6.5i
4.9i
217.4, 217.3g,
215.4h
5.86q
221.2g
227.1g
3.78m
4.22m
4.20m
2.92m
5.34n
3.86m
4.74j
11.21
6.5
5.0
3.84m
3.81l
9.63
4.6
3.1
3.27m
n
2.97
2.55l, 2.47m
8.26
3.3
1.8
6.09j,t, 6.05m,t
6.45j
5.80j, 5.85m
5.57j, 5.63m
1.61m
4.40m
4.23l, 4.23m
2.52m
3.04l
2.67m
m
GBcalc (N)b,c,d GBcalc,otherb,c
12.74
12.23
10.12
7.9
7.0
5.1
6.4
5.5
0.61
6.45
1.78n
4.15k, 4.17l,
4.54m
11.25
3.9
3.5
219.1, 219.4g,
217.0h
218.8g
216.3, 216.0g
215.6, 215.5g
214.3
213.7g
213.3, 211.6h
213.3
211.0, 210.8g
209.5
207.9, 207.5g
207.9, 207.4g
206.9
222.0, 221.9g
224.2g
220.7, 220.5g
219.5, 219.4g
217.4, 216.6g
215.1, 214.7g,
213.2h
215.1, 214.7g
214.5, 214.2g
3.6
2.3
2.0
209.9, 209.6g
208.9
207.8, 208.0g
5.7
217.6
218.6
214.6
213.7
209.6
216.9
210.9
211.4
209.6
208.4
s
205.7
204.4
203.0
226.2t
224.9
220.5
218.6
210.2
212.3
220.4 (O)
s
200.8
203.7
202.6
202.7
199.7
218.1
202.4
205.4, 205.2g
215.3 (NH2),
205.9
215.7 (O)
212.3, 214.0f
212.3
211.1
208.0
206.9
198.3 (SCN)
206.8
205.9
206.5, 206.2g
4.1
42 4-Tf
43 3,5-Me2
44 3,5-(CF3)2
211.6 (ring
protonation,
para),
209.3 (ring
protonation,
ortho)
228.6t
214.1, 213.7g
211.5
8.77
8.59
216.2, 217.7f
209.0 (NO2)
208.5 (NO2)f
206.8 (CN)
213.6 (NO)
192.5 (Tf)
(Continues)
172
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Copyright © 2012 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2013, 26 171–181
BASICITY OF SUBSTITUTED N,N-DIMETHYLANILINES
Table 1. (Continued)
No
45
46
47
48
49
50
51
52
53
54
B
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
C
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
pKa (H2O)
Base/Substitution
2,6-Me2
4-MeO-2,6-Me2
4-Me-2,6-Me2
4-COOMe-2,6-Me2
4-F-2,6-Me2
4-Br-2,6-Me2
4-CN-2,6-Me2
4-NO2-2,6-Me2
3,5-(NMe2)2
2,4-t-Bu2
Anilines
H
N-Me
N-Et
N-Pr
2,6-Me2
N-Me,2,6-Me2
N-Et, N-Me
N,N-Et2
N,N-(n-Pr)2
N,N-(i-Pr)2
c-NC2H4
c-NC3H6
c-NC4H8
c-NC5H10
c-NC6H12
Other bases
NH3
MeNH2
EtNH2
PrNH2
Me2NH
Et2NH
Ph2NH
Me3N
Et3N
Cyclohexylamine
N-Me-cyclohexylamine
N,N-Me2-cyclohexylamine
Ph2NMe
Ph3N
Benzoquinuclidine
1-NH2-naphthalene
1,8-(NH2)2-naphthalene
1,8-(NHMe)2-naphthalene
1-NMe2-8-NHMenaphthalene
1,8-(NMe2)2-naphthalene
4-Me2N-pyridine
3-Me2N-pyridine
2-Me2N-pyridine
pKa (AN)
pKip (THF)
pKa (THF)
5.82m, 61.0m
GBcalc (N)b,c,d GBcalc,otherb,c
GBexpb
221.0, 220.7g
223.0
222.3
218.3, 218.2g
217.8, 217.7g
215.8g
212.5, 212.0g
212.0, 211.8g
219.9
222.5
221.9
217.0
216.4
216.2
210.4
208.8
228.9t
203.0 (CN)
206.4 (NO2)
225.2g
4.63n, 4.58q
4.85m
5.11q
5.04m
3.87m
6.12m
6.02m
6.56q
5.68m
8.14m
10.62p
10.95
7.0i
6.4
5.2i
4.8
203.3g
212.7g
213.4g
204.6f
209.8
209.6
207.9g
218.1g
221.8g
222.5g
218.7
219.8
220.9
214.1g
215.7g
218.7g
221.4g
221.3g
9.25m
10.62m
10.65m
10.53m
10.73m
11.0m
0.78m
9.81m
10.7m
10.68m
11.04m
10.30m
0.86r
3.91r
16.46m
18.37o
18.40m
18.22m
19.02, 18.73o
18.75m
5.97p
17.61o
18.5o
18.35
18.89
18.66
3.94m
9.77p
12.1p
9.61m
6.48m
6.98m
18.62p
17.95p
195.7g
206.6g
210.0g
211.3g
214.3g
219.7g
206.1
219.4g
227.0g
215.0g
223.0f
227.7g
209.5g
226.8g
209.2g
218.0g
222.5g
227.5g
11.7i
11.1i
238.0g
232.1g
225.4g
225.0g
213.6
209.3
238.7t
205.6
209.8
213.7
233.7 (Py)
227.2 (Py)
226.2 (Py)
a
This work, if not noted otherwise, pKa(AN), pKip(THF), pKa(THF) values are those of assigned values for bases which were found
from experimental data using Eqns 4, 8, and 9, respectively. Experimental equilibrium measurement data are given in Tables S1
and S3.
b
GB values are in kcal mol–1(1 kcal mol–1 = 4.184 kJ mol–1).
c
DFT B3LYP 6-311+G** calculations.
J. Phys. Org. Chem. 2013, 26 171–181
Copyright © 2012 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/poc
173
(Continues)
I. KALJURAND ET AL.
Table 1. (Continued)
d
Protonation on amino nitrogen.
Protonation site underlined.
f
G3(MP2) calculations.
g
Ref.[10]
h
Ref.[13]
i
Ref.[15]
j
Values from potentiometric titration, this work. Each value is the average of three determinations; standard deviation was always
less than 0.01 pKa units.
k
Value from potentiometric titration, average of two determinations, this work.
l
Values from the combined method of potentiometry and spectrophotometry; standard deviation was always less than 0.03 of pKa
unit, this work.
m
Refs.[7,8]
n
Ref.[6]
o
Ref.[32]
p
Ref.[19]
q
Ref.[33]
r
Ref.[34]
s
HF eliminates from protonated form.
t
Value corrected for statistics; dibasic compound pKa: log(2); GB: RTln(2) =0.4 kcal mol1; tribasic GB: RTln(3) =0.7 kcal mol1.
e
Sometimes amines have been formally considered as zeroorder members of the homological row of phosphazenes,[19,35]
where DMAs can be viewed as the zero-order members of the
homological row of substituted phenylphosphazenes.[19] It has
been shown[19] that the inclusion of the first phosphazene
fragment into DMA increases its basicity in AN by nearly 10
orders of magnitude, whereas further fragments increase the
basicity by ca five orders of magnitude. The similar trend is
observed in THF and in the gas phase.[35,36] It is of interest to
compare the phenyl-substituted members of the DMA family
with their phosphazene analogues to examine the resulting
basicity changes.
The Brønsted basicity of base B in solvent S is defined by Eqn 1
and is expressed as dissociation constant Ka of the conjugate
acid HB+ of base B or, more commonly, as its negative logarithm
pKa. The following two equations hold for measurements
in water.
Ka
HBþ þ S ⇄ B þ HSþ
Ka¼
(1)
að HSþ ÞaðBÞ
p K a ¼ log K a
að HBþ Þ
(2)
(3)
HBþ þ A ⇄ HBþ s A s
(5)
HBþ þ A ⇄½ HBþ A s
(6)
In THF, the ions are considered to be fully ion paired.[15,16]
Thus, the proton distribution equilibrium between two bases B1
and B2 (Eqn 3) can be presented in the following form:
HBþ
1A
Kd
To exclude the necessity to measure the solvated hydrogen
ion (HS+) activity, which is complicated in nonaqueous solvents,
the following equilibrium between two bases B1 and B2 can be
studied:
B2 þ HB1 þ ⇄ HB2 þ þ B1
but does not describe the actual situation in media of intermediate to low polarity (D ≤ 15. . .20)[37] such as THF, where extensive
ion pairing takes place. The extent of ion pairing of protonated
base cations with anions (A–) depends on the solvent, the size
of the ions, and the charge distribution in the ions. The general
trend is that small, more strongly solvated, ions tend to form
solvent separated ion pairs (Eqn 5), whereas large ions with
delocalized charge tend to form contact ion pairs (Eqn 6).
Ka
HBþ
2A
1=Kd
þ
þ
þ B2 þ HBþ
1 A ⇄B2 þ HB1 þ A ⇄HB2 þ B1 þ A ⇄HB2 A þ B1
(7)
The constants Kd are the dissociation constants of the respective ion pairs, and Ka is the estimate of Ka. The directly measured
quantity is the relative ion pair basicity – ΔpKip – of bases B1 and
B2. It is expressed as follows:
þ The relative basicity of the two bases B1 and B2 (ΔpKa) is
defined as follows:
a HBþ
2 aðB1 Þ
þ
þ
Δ pK a ¼ pKa HB2 pK a HB1 ¼ log
(4)
a HBþ
1 aðB2 Þ
174
The simple acid dissociation equilibrium (Eqn 1) is adequate to
describe the strength of an acid in polar solvents (water, AN, etc.)
wileyonlinelibrary.com/journal/poc
HB1 A
- p K HBþ A- ¼ log Ka Kd
Δ p K ip ¼ p K ip HBþ
A
ip
2
1
HBþ A
Kd 2
a HBþ
2 A aðB1 Þ
¼ log
þ a HB1 A aðB2 Þ
(8)
If the Kd values can be measured or estimated, then the Δ p K a
(an estimate of the Δ p K a) can be found as follows:
Copyright © 2012 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2013, 26 171–181
BASICITY OF SUBSTITUTED N,N-DIMETHYLANILINES
þ HB A
Kd 1
þ
Δ pKa ¼ pKa HBþ
HB
log
pK
¼
Δ
pK
a
ip
2
1
HBþ A
Kd 2
(9)
The Kd values were estimated using the Fuoss equation, as
described previously.[15–18,38] For determination of pKa values in
aqueous media, two well-known methods[39] were used.
The gas-phase basicity (GB) and proton affinity (PA) refer to the
following equilibrium:
ΔGb ;ΔHb
B þ Hþ ⇄ BHþ
using the 6-311+G** basis set. This approach has been demonstrated
by some of us to describe with reasonable accuracy the gas-phase
basicities[17–19,35,36] of a wide variety of relatively simple molecules. All
stationary points were found to be the true minima (Nimag = 0). Unscaled
B3LYP/6-311+G** frequencies were used to calculate the GB and PA values
of the neutral bases, taking into account the zero point frequencies, finite
temperature 0–298 K correction, the pressure–volume work term, and the
entropy term as appropriate. For some bases, the calculations using the ab
initio theory at G3(MP2) level were performed using the same system of
programs.[40] Results of GBs at DFT B3LYP 6-311+G** and G3(MP2) level
of theory are presented in Table 1.
(10)
RESULTS AND DISCUSSION
GB and PA are defined as follows:
G B ¼ Δ G b PA ¼ Δ H b
(11)
The directly measured quantity is the relative basicity of two
bases ΔΔGb:
ΔΔGb
B2 þ B1 Hþ ⇄ B2 Hþ þ B1 ;
The basicity data of DMAs and related bases from this work and
literature in AN, THF, and water and in the gas phase are presented in Table 1 and Tables S1 and S3–S5.
The present results supplement the basicity data in nonaqueous media to an important extent. Experimental values of this
work in aqueous media are in good agreement with the literature values.
(12)
Analysis of experimental and calculated gas-phase basicities
in Table 1
where
ΔΔGb ¼ ΔGb ðB2 Þ ΔGb ðB1 Þ ¼ RT lnK
K¼
pðB1 ÞIðB2 Hþ Þ
pðB2 ÞIðB1 Hþ Þ
(13)
(14)
The p values are the partial pressures of the respective species,
and the I values are intensities of ionic species in mass spectra.
EXPERIMENTAL SECTION
J. Phys. Org. Chem. 2013, 26 171–181
Correlation of the gas-phase basicities of DMAs with
field/inductive, resonance, and polarizability
substituent constants
The calculated and experimental gas-phase basicities of paraand meta- ring-substituted DMAs are correlated with Taft/
Topsom substituent constants sF, sR– and sa[41] according to
Eqn 15.
GB ¼ GB0 þ rF sF þ rR- sR- þ ra sa
(15)
The results of the analysis are presented in Table 2. For calculated basicities, the GBcalc value of NMe2 protonation is taken
even if this protonation is less favored in comparison with the
protonation on substituent. According to our results, the
following ring-substituted DMAs protonate in the gas phase on
the substituent rather than on NMe2: 4-NO2, 4-CHO, 4-COMe,
4-CN, and 4-NO (see the section discussing the protonation site
of DMAs). For correlation of GBexp (this work) and GBexp (NIST),
only bases which, according to the calculations, are predicted to
protonate on NMe2 group were included. For the data from all
three data sources, GBcalc, GBexp (this work), and GBexp (NIST), it
was found that in the case of para-substituted species, the share
of the resonance effect is the largest (ca 50% of the total budget).
The contribution of the field/inductive effect comes next, and
Copyright © 2012 John Wiley & Sons, Ltd.
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175
The purification of chemicals, experimental set-up, and relative basicity
measurement details in AN, THF, and the gas phase as well as the basicity
measurement details in water are provided in the Supporting Information. The ΔpKa values in AN (Table S1) and ΔpKip (Table S3) values in
THF for the equilibria between bases were calculated similarly as
described previously[15–22] using the reference bases from these works.
For the pairs of bases in which one member had small difference in the
spectra of neutral and protonated form (dimethylamine, cyclohexylamine, N-methyl-cyclohexylamine, N,N-dimethyl-cyclohexylamine) was
also used the calculation method[18] in which in addition to the spectra
exact amount of moles of the compounds in titration vessel and added
titrant are taken into consideration for ΔpKa calculations. The measurements in AN and THF are relative, i.e., the basicity difference (expressed
either as ΔpKa in AN or ΔpKip in THF) between the two bases is obtained.
Absolute pKa and pKip values, respectively, were found as in previous
works[15–22] by minimizing the sum of squares of differences between directly measured ΔpKa values (in AN) or ΔpKip values (in THF) and assigned
pKa or pKip values while keeping the pKa or pKip values of the reference
bases[15–22] constant. In THF, the ΔpKa values were calculated with
Eqn 9 using the Kd values of the ion pairs estimated by the Fuoss
equation as described in Refs.[15–18,38] The ionic radii used are given in
Table S2. For two compounds in Table S4, the pKa in water was found
by two methods. The consistency of these results is good. The direct
gas-phase basicity measurement results (ΔΔG b values) are presented in
Table S5. The absolute GB values were found similarly to pKa and pKip
values by keeping the reference GB values from the NIST database[10]
constant. The quantum-chemical computations were carried out using
the Gaussian 2009 series of programs.[40] Density functional theory
(DFT) calculations were performed using the B3LYP hybrid functional.
Full geometry optimizations and vibrational analyses were performed
The experimentally determined GB values for 18 substituted DMAs
and for 5 2,6-Me2-DMAs have been published previously.[10,12]
Correlation of the experimental data presented in detail in this
work with literature values gives the following equation: GB (this
work) = 0.990 (0.013) GB (NIST) + 2.49 (2.77), r2 = 0.997,
S = 0.26, n = 18. For the ring-substituted 2,6-Me2-DMAs, quite
similar results are obtained: GB (this work) = 0.990 (0.023) GB
(NIST) + 2.45 (4.88), r2 = 0.998, S = 0.18, n = 5. This means that
data published in NIST derived partially from the present data
are consistent with the absolute GB values derived from the original data but are in general lower by 0.3 kcal mol–1. We recommend
using the experimental GB values determined in this work.
I. KALJURAND ET AL.
Table 2. Statistical analysis of GB of substituted DMAs with field/inductive, polarizability, and resonance substituent constantsa
Series
4-X substituted
4-X substituted
4-X substituted
3-X substituted
3-X substituted
3-X substituted
DMA
DMA
DMA
DMA
DMA
DMA
b
GBcalc (N)
GBexp (this work)c
GBexp (NIST)c
GBcalc (N)d
GBexp (this work)f
GBexp(NIST)h
GB0
S (GB0)
rF
S (rF)
r–R
S (r–R)
ra
S (ra)
S
r2
n
216.48
217.82
217.76
219.41
217.44
217.31
0.851
0.43
0.50
1.04
0.93
0.18
20.76
17.26
18.04
22.02
16.73
17.70
1.69
0.84
1.28
1.83
1.22
0.39
28.66
20.87
21.15
2.19
1.46
1.69
— g
— g
— i
— i
7.41
6.33
6.16
0.32
5.01
5.56
1.80
1.13
1.35
1.62
1.74
0.48
1.41
0.58
0.62
1.02
0.63
0.22
0.974
0.993
0.987
0.967
0.976
0.998
18
10
8
8
9
7
— e
— e
s values are taken from Table IX of Ref.[41]
GB value on NMe2 protonation is taken.
c
Only bases that protonate on NMe2 are included.
d
Excluding 3-SF5, 3-CHO, 3-Cl, and 3-MeO substituted DMAs and unsubstituted DMA. Excluding also polarizability constants
following is obtained: GB = 219.28 (0.72) – 21.97 (1.66) • sF, S = 0.93, r2 = 0.967.
e
Assumed not to be present; if included, then the following is obtained: GB = 218.40 (1.07) – 21.25 (1.63) • sF –6.98 (4.13) • sR–
–3.03 (2.42) • sa, S = 0.87, r2 = 0.981.
f
Excluding 3-F, 3-CN, substituted DMAs, and unsubstituted DMA.
g
Resonance effect assumed not to be present; if resonance constants are included, then the following is obtained: GB = 217.65
(0.88) – 16.82 (1.05) • sF –2.79 (2.05) • sR– –5.17 (1.63) • sa, S = 0.59, r2 =0.982.
h
Excluding 3-CN-DMA.
i
Resonance effect assumed not to be present; if resonance constants are included, then it follows: GB = 217.37 (0.22) – 17.79
(0.44) • sF –0.52 (0.77) • sR– –5.33 (0.62) • sa, S = 0.23, r2 = 0.998. Low numerical value and high standard deviation value of
rR– confirm that the contribution from the resonance effect is not present.
a
b
polarizability has the lowest contribution. The absolute values of
the regression coefficients found in this work are somewhat
higher than those obtained in the literature (rF = 14.4 (1.1),
rR– = 12.7 (1.0), ra = 2.1 (1.1), S = 0.8, r = 0.9934 (r2 = 0.987),
n = 14),[11] (rF = 14.7 (1.0), rR + = 14.6 (1.0), ra = 0.7 (1.4),
S = 0.9, r = 0.992 (r2 = 0.984), n = 11);[25] however, the proportions
of substituent effects are similar.
As expected, in the meta-substituted series, the field/inductive
effect has the highest contribution. This is in all series again
somewhat higher than that in the literature[11] (rF = 15.2 (1.0),
ra = 4.9 (1.5), S = 0.8, r = 0.9840 (r2 = 0.968), n = 11, resonance
term rR–sR– was not included). The poorest correlation is
observed with GBcalc values. In this series also, the polarizability
displays an unimportant contribution. The numerical value of
its coefficient is lower than its confidence limit (derived from
standard deviation by multiplying it with the corresponding
t-value). However, in experimental GB series, for data from this
work and from NIST,[10] the polarizability coefficient is significant,
and it is comparable with the results from literature.[11]
The analysis of basicity data of DMAs in water, AN, and THF
reveals that in all these solvents, the polarizability effect for the
para- and meta-substituted series is statistically unimportant.
The regression coefficients (Table S6) for the resonance effect
of the para-substitution series and the field/inductive effect for
the para- and meta- substituted series decrease several times if
compared with the gas phase.
Effect of the stepwise change of amine structure on basicity
in various media
176
Stepwise methylation of ammonia increases its gas-phase
basicity non-additively (Scheme 1); the first methyl group has
the largest effect.
The first cyclohexyl group has almost two times higher base
strengthening effect on ammonia than that of the methyl group,
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Scheme 1. Basicity change in the gas phase upon stepwise change of
amine structure. Numbers below structures show absolute GB values in
kcal mol–1; numbers above or next to the arrows show basicity differences
mainly due to its more than two times higher polarizability
(sa (Me) = 0.35 vs sa (c-hexyl) = 0.76). Analogously to the
methylation of the ammonia series, the non-additivity is observed on further methylation of cyclohexylamine, but the basicity increase is less pronounced. Introduction of a phenyl group
into ammonia – leading to aniline – increases basicity by 7.6 kcal
mol–1. Non-additivity of stepwise N-methylation is even more
Copyright © 2012 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2013, 26 171–181
BASICITY OF SUBSTITUTED N,N-DIMETHYLANILINES
J. Phys. Org. Chem. 2013, 26 171–181
Scheme 2. Basicity change in water upon stepwise change of amine
structure. Numbers below structure show absolute pKa values; numbers
above or next to the arrows show the change of pKa
ion to triphenylammonium ion. Reasons 1 and 3 dominate.
Similar trend, basicity decrease is observed on stepwise replacement of methyl groups with phenyl groups of tertiary
amine trimethylamine. In this case, the direction of basicity
change is the same as in the gas phase. Here, all compounds
are tertiary amines, i.e., the number of possible hydrogen
bonds is the same in all conjugate acids, and the reason for
the basicity decrease is different from that in the previous
series. The main contributor on basicity change is, similarly to
gas phase, the base-weakening effect from the unfavorable
effect of resonance and steric strain.
The comparison of aqueous pKa values of ring-substituted
DMAs from this work and literature reveals that the 4-NO-DMA
deviates from the otherwise very good linear correlation
between the common compounds: pKa (H2O literature) = 0.11
(0.07) + 0.98 (0.01) pKa (H2O this work), n = 6, r2 = 0.999,
S = 0.04. Either our pKa value (4.17) or the literature value (4.54)
for this compound is wrong. A possible explanation to this
inconsistency may be that this compound is light-sensitive
and can decompose if exposed to UV light or strong chemical oxidants in acidic solution or during storage as bulk.[42]
Decomposition of this compound during experiment can be
observed as spectrum change. However, we did not observe
problems with spectrum stability or diffuse isosbestic points
with our solutions. Also, two different pKa determination
methods on different days and with different batches of solutions gave the same results. We are unable to assess if such
artifacts were present in the measurements made for the
literature value.
In AN (Scheme 3), the stepwise introduction of substituents
changes the basicity of amine in a similar way as in water. The
similarities of the trends in water and AN confirm the importance
of solvation of the protonated bases by hydrogen bond acceptor
interaction by the AN solvent.
Copyright © 2012 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/poc
177
expressed in aniline than in cyclohexylamine. Introduction of the
first methyl group into aniline increases its basicity by 9.4 kcal
mol–1, only slightly lower change than produced by methylation
of ammonia.
The basicity increase on consecutive phenylation of ammonia
is non-additive: 7.6, 2.8, and 3.4 kcal mol–1, respectively. The addition of the second phenyl group has the lowest effect. In this
series, the base strengthening effect is mainly determined by
higher polarizability of the phenyl group (sa (Ph) = 0.81); this
effect stabilizes the protonated form. This effect is somewhat
decreased by the opposite resonance (mesomeric) effect,
(sR– (Ph) = 0.22) and the smaller field/inductive effect (sF (Ph) =
0.10), which both stabilize the neutral form. Stepwise substitution of methyl groups in trimethylamine for phenyl groups
weakens the basicity by 2.0, –3.8, and 4.1 kcal mol–1. In
this series, the gain from polarizability (sa (Me) = 0.35 vs sa
(Ph) = 0.81) and the small field/inductive effect is partly lost.
The net base weakening effects from the resonance effect and
steric strain dominate. Both of these findings suggest that the
addition of a second and third phenyl group introduces more
steric strain into the molecule. Replacement of the Me groups
in DMA with Et groups leads to moderate strengthening of the
base by ca 4 kcal mol–1; further introduction of methylene units
has a very small effect. Formation of a three-member ring from
NMe2 of the DMA leads to base weakening by 2 to 3 kcal mol–1.
This is because the lone electron pair of the nitrogen atom,
which is a part of a three-membered ring, has more s character
and is therefore held more tightly by the N atom. Inclusion of additional methylene units into this ring strengthens the resulting
base non-additively until reaching plateau upon formation of a
six-membered ring. Additional base strengthening by 5.4 kcal
mol–1 is achieved upon formation of a covalent bond between
the orto carbon of the phenyl ring and the para carbon of the
piperidinyl ring of N-phenylpiperdine by formation of benzoquiniclidine, thus introducing polarizable alkyl group into the ortho
position of formal N,N-dialkylaniline.
In water (Scheme 2), the effect of structural changes on basicity is significantly different from the gas phase.
Basicity change on stepwise introduction of substituents into
ammonia is, in addition to the field/inductive and resonance
effect, strongly influenced by solvation, especially by the hydrogen bonding of water to the NH+ bonds of the protonated
amine. The advantage of cyclohexyl group over methyl group
in base strengthening of ammonia that was observed in the
gas phase is almost lost in water due to strong reduction of
polarizability in aqueous solution. Substitution of methyl group
with cyclohexyl group strengthens the primary amine only
slightly and makes secondary amine stronger by 0.3 pKa units
and tertiary amine by 0.5 pKa units. This shows that water has a
strong stabilizing effect on the cation when forming the
hydrogen bonds. Contrary to the monoalkylamines, further
methylation of nitrogen in aniline increases the basicity of the
base additively. Stepwise phenylation of ammonia reduces
basicity by 4.65, –3.82, and 4.69 pKa units. The observed
effect is in the opposite direction compared with the basicity
change of the same series in the gas phase. The main reasons
for the basicity decrease in this series are (i) the stabilization of
the neutral form by resonance, which is lost on protonation;
(ii) the slight destabilization of the protonated form by the inductive effect of the phenyl substituents; and (iii) the loss of N–H+
bond solvation by reduction of the number of N–H+ bonds,
which can form N-H+OH2 bonds when going from ammonium
I. KALJURAND ET AL.
Scheme 3. Basicity change in AN upon stepwise change of amine structure. Numbers below the structures show absolute pKa values; numbers
above or next to the arrows show the change of pKa
Protonation site of DMAs in the gas phase and in solution
178
It has been suggested[24] that in DMA the protonation on
nitrogen is expected to be by 1.2 kcal mol–1 more favorable than
the protonation on the para-carbon atom of the benzene ring.
Our current DFT B3LYP 6-311+G** calculations confirm those
findings: GB(N) = 216.2 kcal mol–1, GB(C4) = 211.6 kcal mol–1,
and GB(C2) = 209.3 kcal mol–1. For several compounds, we calculated the GB values on the assumption that the ring-substituted
DMA base is protonated on a basicity center which is different
from NMe2, i.e., on the substituent. Calculation results from
Table 1 show that the protonation on the substituent is favored
over NMe2 protonation for the following compounds: 4-NO2DMA (208.5 kcal mol–1 vs 200.8 kcal mol–1 on NMe2), 4-NODMA (213.6 kcal mol–1 vs 202.6 kcal mol–1 on NMe2), 4-CN-DMA
(206.8 kcal mol–1 vs 203.7 kcal mol–1 on NMe2), 4-COMe-DMA
(220.4 kcal mol–1 vs 210.2 kcal mol–1 on NMe2), and 4-CHODMA (215.7 kcal mol–1 vs 205.9 kcal mol–1 on NMe2). 4-COOMeDMA could be protonated on the substituent. Its experimental
GB is 3.0 kcal mol–1 higher than the calculated GB(N); however,
this difference is not large enough to be sure about the protonation site. FT-ICR-MS experiments reveal that certain anilines
indeed preferentially protonate on substituents in the gas
phase. The evidence for this and discussion concerning the
protonation site of DMAs and/or anilines can be found in several
literature sources.[25–31]
2,6-Me2-DMA is ca 4. . .5 kcal mol–1 stronger base than DMA,
which is due to the polarizability effect of the methyl groups
(sa(Me) = 0.35) in the phenyl ring as well as due to the weakening of the resonance between the ring and the Me2N substituent
by steric hindrance in the neutral 2,6-Me2-DMA. At the same
time, calculations show that 4-CN-2,6-Me2-DMA and 4-NO2-2,
6-Me2-DMA will not protonate on the substituent in phenyl ring.
This is because 2,6-Me2 substituents in ortho positions to the
NMe2 group destroy, due to the steric hindrance, the direct
resonance between NMe2 and acceptor groups (NO2, NO etc)
in the 4-position in the respective neutrals. Protonation on these
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substituents is even less favored as compared with protonation
on the same substituents in DMA: by 3.8 and 2.6 kcal mol–1
for the CN and NO2 substituent, respectively. For 4-SF5-DMA,
the calculations show that HF eliminates from the substituent
SF5. The inconsistency of the experimental and calculated GB
values for 3-SF5-DMA may be of the same origin.
From comparison of gas-phase and solution basicities, the
unexpected strength of 4-NO-DMA in solution is observed. Comparison of the gas-phase calculation results of 4-NO2-DMA, 4-NODMA, and DMA and the relative values of substituent parameters
of the corresponding compounds would suggest that its pKa in
water, THF, and AN solvents should be slightly higher than that
of 4-NO2-DMA. However, its pKa in AN is by only 0.18 pKa units
lower, in water by 0.98 pKa units lower, and in THF by 0.8 pKa
units lower than that of the parent compound DMA.
4-NO2-DMA and 4-NO-DMA have quite similar UV–vis spectra
in AN in base form. They have a strong absorbance maximum
at 395 and 422 nm, respectively. This absorbance corresponds
to the intramolecular charge transfer between the NMe2 and
NO2 or NO groups, respectively. Upon protonation of 4-NO2DMA, this peak is lost completely; only the weak absorbance
corresponding to the phenyl ring with absorbance maximum
at 250 nm remains. This means that in AN, this compound protonates on the dimethylamino group, thus eliminating the possibility of such intramolecular charge transfer. Upon protonation
of 4-NO-DMA, intramolecular charge transfer absorbance is
preserved; it only shifts by 74 nm toward shorter wavelength
(to 348 nm) in AN. In water, the same shift is 92 nm (from 440
to 348 nm) and in THF 57 nm (from 412 nm to 355 nm). This indicates that polar resonance is preserved in this molecule after
protonation in all these solvents. As NO group has no resonance
donor ability, the resonance is only possible if the substituents
on phenyl ring are NMe2 and NOH+. These spectral features, as
well as the high pKa value, suggest that in AN, THF, and water,
4-NO-DMA is with high probability protonated on the NO group.
This is in agreement with previous findings.[26]
Correlation between basicities in different media and
between basicities of different compound families
Statistical analysis of basicities in different media according to
Eqn 16 was carried out. The results are presented in Table 3.
y ¼ ax þ b
(16)
where x and y are basicities in the first and second medium,
respectively, or basicities in a particular medium of a first and a
second compound family, respectively.
In correlation of the pKa values in water and AN, the most
deviating pKa values are 4-NO- and 4-NO2- substituted DMAs
(Fig. 1).
This is caused by the substituent solvent assisted resonance
(SSAR) effect[11,44,45] in water, in which the electrophilic solvation
of the NO or NO2 substituent by water molecules enhances
substituent influence on the base strength and makes these
two compounds weaker bases in water than it would be
expected from the basicity values in AN. By leaving these two
SSAR-susceptible compounds out from the correlation, it is observed that AN is 1.33 (s (slope) = 0.06) times better differentiating solvent than water for DMAs. This is in good agreement with
previous findings[19] where the value 1.31 (s(slope) = 0.05) was
obtained for this parameter over a wide range of basicity and
using a wide selection of bases.
Copyright © 2012 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2013, 26 171–181
BASICITY OF SUBSTITUTED N,N-DIMETHYLANILINES
Table 3. Statistical analysis of solvent attenuation of the substituent effects on the basicity values water, AN, and THF and correlation of basicities of DMAs and phosphazene analogues
No
Argument (x)
Value (y)
a
b
s (a)
s (b)
S
0.33
0.26
0.39
0.21
1
2
pKa(H2O)
pKa(H2O)
pKa(AN)
pKa(AN)
1.22
1.33
5.35
4.80
0.08
0.06
3
3a
pKa(H2O)
pKa(H2O)
pKa(THF)
pKa(THF)
1.34
1.21
1.70
1.35
0.08
0.05
4
5
pKa(AN)
pKa(H2O)
pKa(THF)
GB
0.99
3.97
6.40
198.0
0.06
0.38
6
pKa(AN)
GB
3.06
182.1
0.25
7
8
9
10
11
pKa(THF)
GB(DMA)
pKa(DMA) in AN
pKa(DMA) in THF
pKa(DMA) in H2O
GB
GB(PhP1(pyrr))a
pKa(PhP1(pyrr))a in AN
pKa(PhP1(pyrr))a in THF
pKa(PhP1(pyrr))a in H2O
3.00
0.709
0.740
0.498
0.400
202.2
97.6
13.76
12.84
9.554
0.28
0.080
0.019
0.009
0.024
r2
n
Comments
0.963 11 All
0.985 9 Excluding 4-NO2-DMA,
4-NO-DMA
0.36 0.29 0.970 10 Excluding 4-NO-DMA
0.18 0.13 0.994 7 Excluding 4-NO-, 4-MeO
and 3-MeO-DMA
0.59 0.27 0.975 10
1.71 2.00 0.877 17 Excluding 4-NO2-DMA,
4-NO-DMA, 4-CN-DMA
2.65 1.16 0.961 8 Excluding 4-NO2-DMA,
4-NO-DMA
1.19 1.30 0.951 8 Excluding 4-NO-DMA
17.5
1.05 0.963 5
0.19 0.09 0.998 5
0.06 0.030 0.999 4
0.117 0.066 0.990 5 Excluding 4-NO2-DMA
a
GB and pKa data of phosphazenes are taken from Refs[15–22,36,43]
Figure 1. Correlation of the basicities of the studied DMAs in water
and acetonitrile
J. Phys. Org. Chem. 2013, 26 171–181
on Figure 2 suggests that in water 4-NO-DMA is not an amino
base but protonates on the NO group.
Figure 3 demonstrates that in AN the SSAR effect is not
expressed or is much weaker than in water. The correlation
shows that the calculated GB value of NMe2-protonated
4-NO2-DMA is located on the overall correlation line. This means
that in AN, it is an amino base, and in the gas phase, it is an O
base. The GB value of amino-protonated 4-NO-DMA and pKa value
in AN deviate from the general trend. This supports the idea that
in these media it is an O base. Similar deviation is seen in correlation of the pKa values in THF and GB values.
Comparison of basicities of DMAs and phenyl-substituted
phosphazenes in different media
Excellent correlation (Table 3 and Fig. S4) of phenyl-substituted
DMAs and the corresponding PhP1(pyrr) phosphazenes in AN
Copyright © 2012 John Wiley & Sons, Ltd.
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179
Correlation of basicities of DMAs in water and in THF (Fig. S1)
brings out that besides the 4-NO-DMA, also 3-MeO and 4-MeO
substituted DMAs are weaker bases in water than could be
expected from the correlation. A possible reason is a weak
hydrogen bonding of water molecules to the MeO group,
thereby making it a weaker resonance donor group. The
slope 1.21 (s(slope) = 0.05) agrees well with the slope 1.14
(s(slope) = 0.06) reported in the literature[15] for a wider selection
of bases. The same observation is made for correlation of
basicities in AN and THF; the slope 0.99 (s(slope) = 0.06) agrees
with slope 0.92 (s(slope) = 0.02).[15]
Correlation of GBs with pKa(H2O) has slope 3.97. The extent of
attenuation of the substituent influence when going from the
gas phase to water is thus 3.97log(e)/RT = 2.9 times. For AN
and THF, the attenuation factors are somewhat lower: for AN
3.06log(e)/RT = 2.2 and for THF 3.00log(e)/RT = 2.2.
The outlying point of 4-NO-DMA (experimental pKa in water
and calculated GB value corresponding to amino protonation)
Figure 2. Correlation of the basicities of the studied DMAs in gas phase
and water. Protonation center on substituent is underlined
I. KALJURAND ET AL.
Figure 3. Correlation of the basicities of the studied DMAs in the gas
phase and acetonitrile. Protonation center on substituent is underlined
180
confirms that in AN the SSAR effect is not expressed on 4-NO2-DMA.
Correlation of basicities in water and AN reveals that 4-NO2 substituted phosphazene is (Fig. S7) ca 0.5 pKa units weaker base in AN
than expected from the correlation. This is because in the phosphazene base the para-NO2 group is in strong resonance with the
negative charge of the ylidic protonation center[46] therefore, the
SSAR effect of water is significant.
The slopes of the correlation lines of basicities of phenylsubstituted DMAs and PhP1(pyrr) phosphazenes in the gas phase
and THF, water, and AN are as follows: 0.69, 0.50, 0.38, and 0.74,
respectively. This means that the basicity of PhP1(pyrr) phosphazenes is in all of these media less sensitive toward substitution in
the aromatic ring than the basicity of DMAs. In the reference
medium, gas phase, this sensitivity difference is caused by the
contribution of the ylenic structure in the substituted PhP1(pyrr)
series and delocalization of the positive charge of the protonated form into the large phosphorane moiety.[19] Lower slope
values in water and THF are caused by the added solvation
effects. The molecules of these solvents can specifically solvate
cations by acting as bond acceptors. The protonation centers
in DMAs are less sterically hindered than in PhP1(pyrr) phosphazenes, and the solvent molecules can thus stabilize the protonated DMA cations better. AN has lower basicity than water or
THF and is a weaker HB acceptor. Therefore, in this solvent, the
slope is not lower but even slightly higher than in the gas phase.
Koppel et al.[35] considered ammonia to be a zero-order phosphazene. It was observed that inclusion of the first phosphazene
subunit increases the basicity much more than addition of the
following units. DMA and its corresponding phenyl-substituted
analogues can be considered as zero-order phenylphosphazenes
PhP1(dma). Similar trend as in Ref[35] is seen when going from
the DMA family to the higher phenylphosphazenes (Figs 4
and S8).
Para-substituted phenyl homologues exhibit a similar trend
with the non-substituted series in AN. It is seen that phenylphosphazenes are less sensitive toward substitution in aromatic ring
than are DMAs. The difference of basicities of 4-MeO and 4-CF3
substituted DMAs is 4.2 pKa units; in case of PhP1(pyrr) and
PhP2(pyrr) with the same substituents, the differences are
respectively 3.0 and 2.9 pKa units, i.e., the influence of the substituent decreases ca 1.4 times upon addition of the phosphazene
subunits. In THF, it is difficult to do the same analysis as in AN
because some data points are missing. The difference of
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Figure 4. Dependence of the pKa values in acetonitrile of substituted
phenylphosphazenes on the number of phosphazene units
basicities of 4-MeO and 4-CF3 substituted DMAs in THF is 4.4
pKa units; in case of PhP1(pyrr) and PhP3(pyrr) with the same substituents, the differences are, respectively, 2.2 and 2.6 pKa units.
The sensitivity toward substitution in higher phosphazene phenyl
ring in these series decreases 1.7 to 2 times if compared
with DMA.
Comparison of basicities of DMAs and 2,6-Me2-DMAs in the
gas phase
Correlation of substituted DMAs with the corresponding
2,6-Me2-DMAs (Fig. S9) is valuable because it provides further
support to the earlier made claim that 4-NO2- and 4-CN-DMA
are not amino bases. As explained earlier, 4-NO2-2,6-Me2-DMA
and 4-CN-2,6-Me2-DMA are amino bases. The deviation of the
points of 4-NO2 and 4-CN from the correlation line thus
evidences that the corresponding DMAs are not amino bases.
4-COOMe substituted derivative lays close to the correlation line,
so its DMA and 2,6-Me2-DMA derivatives behave as amino bases
in the gas phase. Correlation of 4-MeO, 4-Me, 4-COOMe, 4-Br, 4-F,
and unsubstituted DMAs with the corresponding 2,6-Me2-DMAs
gives the following correlation equation: GB (2,6-Me2-DMA) =
34.0 (15.7) + 0.86(0.07) GB (DMA), n = 6, r2 = 0.972, S = 0.53.
CONCLUSIONS
Structure–Basicity relationships for the DMA family and related
bases in water, AN, and THF and in the gas phase have been
determined. By comparison of gas-phase basicity shifts induced
by stepwise substitution, starting from ammonia and ending at
triphenylamine, it was observed that the solvent effects of water
and AN exceed the structural effects on intrinsic basicity. It was
shown that the influence of the substituent in the phenyl ring
on DMA basicity is reduced by two to three times when going
from the gas phase into the abovementioned condensed media.
This effect is the strongest in water. Substituents in the phenyl
ring of phenylphosphazenes have lower influence on basicity
than those in DMAs in all three solvents and in the gas phase.
The difference is the highest in water and the lowest in AN.
In the gas phase 4-NO, 4-NO2, 4-CN, 4-COMe and 4-CHO
substituted DMAs protonate on substituent whereas in solvents
only 4-NO-DMA will probably protonate on substituent. At the
same time, 4-NO2 and 4-CN-2,6-Me2-DMAs protonate on the
NMe2 group in the gas phase.
Copyright © 2012 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2013, 26 171–181
BASICITY OF SUBSTITUTED N,N-DIMETHYLANILINES
Acknowledgements
This work was supported by Grants 6699, 8689, and 8162 from
the Estonian Science Foundation, by the targeted financing
project of Ministry of Education and Science of Estonia
SF0180089s08 and by the Estonian Centre of Excellence HIGHTECHMAT SLOKT117T.
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[3] M. Sittig. Handbook of Toxic and Hazardous Chemicals and
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