Equilibrium of acyl transfer between pyridine N-oxides and their acylonium salts

Article abstract of DOI:10.1134/S1070363208060248

Transfer of acyl groups from N-acyloxypyridinium salts to pyridine N-oxides in acetonitrile was studied. The equilibrium constants of acyl exchange were determined. These quantities vary in the range covering eight orders of magnitude, depending on the st

Full text of DOI:10.1134/S1070363208060248

ISSN 1070-3632, Russian Journal of General Chemistry, 2008, Vol. 78, No. 6, pp. 1241–1246. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © V.I. Rubachenko, G. Schroeder, K.Yu. Chotii, V.V. Kovalenko, A.N. Red’ko, B. Lenska, 2008, published in Zhurnal Obshchei
Khimii, 2008, Vol. 78, No. 6, pp. 1013–1018.
Equilibrium of Acyl Transfer between Pyridine N-Oxides
and Their Acylonium Salts
V. I. Rubachenkoa, G. Schroederb, K. Yu. Chotiia,
V. V. Kovalenkoa, A. N. Red’koa, and B. Lenskab
a Litvinenko Instituteof Physical Organic and Coal Fuel Chemistry, National Academy of Sciences of Ukraine,
ul. R. Lyuksemburg 70, Donetsk, 83114 Ukraine
e-mail: rybach@stels.net
b Adam Mickiewicz University, Poznan, Poland
Received August 17, 2007
Abstract—Transfer of acyl groups from N-acyloxypyridinium salts to pyridine N-oxides in acetonitrile was
studied. The equilibrium constants of acyl exchange were determined. These quantities vary in the range
covering eight orders of magnitude, depending on the structure of the reagents, and are independent of the
structure of the acyl group.
DOI: 10.1134/S1070363208060248
Equilibrium constants are important physico-
chemical quantities characterizing the reactivity [1, 2].
However, for many organic reactions, in particular,
acylation, the available thermodynamic quantities are
few or lacking at all [3, 4]. Therefore, the cor-
responding kinetic data are most often treated using the
ionization constants of the reagents [5, 6]. This
replacement requires the observance of the linear free
energy relationship, which is not always the case. For
example, in the coordinates of the Brønsted equation
the nucleophilicity of organic compounds changes
jumpwise with a change in the nature of the base
center [7, 8]. Therefore, the equilibrium constants of
acyl transfer reactions are required not only as
characteristics of numerous organic [4] and biochem-
ical [5] transformations, but also as necessary
parameters for analysis and prediction of their
reactivity using modern physically substantiated
correlation schemes [9, 10].
structure of the acyl group. For this purpose, we
determined by UV and IR spectroscopy and kinetic
method the equilibrium constants of reactions (1) in
CH3CN solutions at 298 K, with Асyl = CH3CO–
(Ac1), (CH3)2NCO– (Ac2), C6H5CO– (Ac3), 4-morpho-
linocarbonyl (Ac4), 1-piperidinocarbonyl (Ac5), and
(C6H5)2NCO– (Ac6); X– = BPh4– and Nu=.
The results are given in Table 1. Also given are the
quantities that we obtained previously and also the
heats of the reactions, calculated by the AM1 method
taking into account the solvent (CH3CN) effect in the
COSMO approximation. The equilibrium constants of
reactions (1) were obtained (except system no. 29) for
the reactions in which the leaving group (Nuj) or
nucleophile (Nui) is 4-(4'-N,N-dimethylaminostyryl)
pyridine N-oxide, Nu9 in our notation. This choice is
dictated by the reliability requirements. In CH3CN, 4-
(4'-N,N-dimethylaminostyryl)pyridine N-oxide (λmax
395 nm) and its О-acyl salts (λmax 510 5 nm) have
well-resolved absorption bands which are not
superimposed on bands of other participants of
reaction (1). Their very high intensity (ε, respectively,
Previously [11, 12] we examined the effect of
structural factors on the equilibrium constants and
heats of the exchange of acetyl and dimethylcarbamoyl
groups between pyridine N-oxides.
36000 and 59000
5000 l mol–1 cm–1) allowed
simultaneous determination of the equilibrium
concentration of the starting compounds and products
and reliable monitoring of the reaction kinetics [14]
with any combination of participants of reaction (1).
The accuracy of the measured quantities is particularly
Acyl-Nui+,X– + Nuj ҙ Acyl-Nuj+,X– + Nui.
(1)
In this study we examined how the equilibrium
characteristics of reaction (1) are influenced by the
1241

1242
RUBACHENKO et al.
O
O
O
N
N
N
Cl
(Nu1)
(Nu2)
(Nu3)
N
N
C2H5
O
O
(Nu11)
(Nu12)
CH3
H3C
H3C
CH3
N
N
N
CH3
OCH3
N
O
O
O
(Nu4)
(Nu5)
(Nu6)
(Nu7)
(Nu8)
O
O
N
H3C
(Nu13)
(Nu14)
O
N
O
O
O
O
N
N
N
N(CH3)2
CH3CHCH3
CH HC
CH HC
O
O
N
OCH3
(Nu15)
(Nu16)
N(CH3)2
(Nu9)
H3C
N
(Nu10)
N
N
O
H3C
H3C
important in this case, because pairwise subtraction of
the quantities (log Ki9 – log Kj9 = logKij) for reactions
with the same nucleophile (or leaving group) allows
calculation of the constants as elements of the
corresponding i–j matrix, most of which cannot be
directly determined experimentally but are necessary,
e.g., for correlation analysis [10–12]. A special
example from the benzoyl transfer (cf. system nos. 26,
27, and 29 in Table 1) confirms that the calculated
(1.76 – 0.42 = 1.34) and experimental (log K2,4 1.12)
values coincide within the measurement errors.
hence the lower the basicity), which is quite consistent
with the concept of the mechanism of nucleophilic
substitution reactions [3–5]. At the same time, the
structure of the acyl group as a fragment of the
acylonium cation, potentially capable to affect the
equilibrium of reaction (1), exerts virtually no
influence. For example, the equilibrium constants in
system nos. 2, 16, 20, 23, 26, 30 or nos. 5, 19, 25, 28,
32 coincide within the measurement error.
Let us consider formally structural factors affecting
the equilibrium under consideration. The entropy
changes in symmetrical reactions are insignificant [9,
15, 16]; therefore, the free energy of reaction (1) can
be presented as follows:
As seen from Table 1, the equilibrium constants of
reaction (1) vary in the range covering eight orders of
magnitude depending on the structure of salts, but
these changes are associated virtually exclusively with
the basicity of the leaving group and/or nucleophile
(see, e.g., system nos. 1 and 5, 16 and 19, 30 and 32).
The parameter log K is the larger, the higher the
electron-withdrawing power of substituents in Nui (and
ΔGij ≈ E(Ac-Nui) – E(Ac-Nuj),
(2)
where E(Ac-Nui) and E(Ac-Nuj) are the energies of the
breaking and forming bonds, respectively, which, in
turn, can be presented as follows:
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EQUILIBRIUM OF ACYL TRANSFER BETWEEN PYRIDINE N-OXIDES
1243
Table 1. Thermodynamic characteristics (log Kij, ΔGij = –RTlnKij, –ΔHij)а of reaction (1) (solutions in CH3СN, 298 K)
pKBH of Nui [6, 13],
+
b
System no.
Nui
Acyl
log Kij
ΔGij, kJ mol–1
–ΔHij, kJ mol–1
H2O/CH3CN
1
2
1
2
Ac1
Ac1
Ac1
Ac1
Ac1
Ac1
Ac1
Ac1
Ac1
Ac1
Ac1
Ac1
Ac1
Ac1
Ac1
Ac2
Ac2
Ac2
Ac2
Ac5
Ac5
Ac5
Ac6
Ac6
Ac6
Ac3
Ac3
Ac3
Ac3
Ac4
Ac4
Ac4
2.72
1.76
0.33/9.06
0.79/9.97
0.92/10.30
1.29/11.00
2.05/12.37
3.25/14.5c
3.88/15.62
1.10/10.6c
1.03/10.25
1.34/11.0c
1.21/10.8c
1.37/10.27
–15.6
–10.0
–5.9d
–2.7
7.7
7.46
–0.01
1.96
3
3
1.22 (0.84)
0.48
4
4
–1.65
–7.00
–17.37
–23.64
1.45
5
5
–1.35
6
6
–3.80
–5.26
0.86
21.7
30.0
–4.9
–6.3d
–1.7
–5.3
–6.9
–4.0
7.1
7
7
8
8
9
10
11
12
13
14
15
16
2
1.28 (0.93)
(0.30)
0.93
–3.08
–1.16
–0.73
–3.02
0.76
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
1.21
(0.71)
–1.25
–4.21
(1.99)
1.30 (1.28)
0.51 (0.51)
–1.57 (–1.62)
1.79
1.26/10.9c
–
–8.38
–19.14
0.21
–
24.0
–11.3
–7.4d
–2.9
9.1d
0.79/9.97
0.92/10.30
1.29/11.00
2.05/12.37
0.79/9.97
1.29/11.00
2.05/12.37
0.79/9.97
1.29/11.00
2.05/12.37
0.79/9.97
1.29/11.00
2.05/12.37
0.79/9.97
0.79/9.97
1.29/11.00
2.05/12.37
3
2.36
4
–1.49
–7.01
0.51
5
2
–10.2
–1.8
7.4
4
0.32
–1.06
–7.04
0.74
5
–1.30
2
1.85
–10.5
–2.6
7.7
4
0.46
–0.98
–8.01
0.44
5
–1.36
2
1.76
–10.0
–2.4
7.1
4
0.42
–1.19
–6.83
–0.75
0.50
5
–1.24
1.12e
2
–5.9
–10.3
–1.3
8.2
2
1.80
4
0.23
–0.97
–7.04
5
–1.45
b
a
j 4 in system no. 29 and 9 in the other systems. The error of the UV spectrophotometric determination of constants does not exceed
0.05 log unit, and that of kinetic determination, 0.10 log unit. The values obtained from kinetic measurements as K = k1/k–1 are given in
c
d
parentheses. Calculated by the equation pKBH+(CH3CN) = 1.83pKBH+(H2O) + 8.56 [13]. Averaged equilibrium constants used.
e Measured by IR Fourier spectroscopy.
E = Е0 + ΔE; ΔE = f(Nux).
(3)
reaction constant ρ. This quantity characterizes the
sensitivity of a given equilibrium to structural changes
in the reactants [17].
Assuming [17] that f(Nux) = ρσx or f(Nux) = ρ'pKx,
we obtain for any Nui-Nuj pair
ΔGij = ρ(σi – σj) = ρ'(pKi – pKj).
(4)
The most suitable method for characterizing the
structure of acylonium cations is IR spectroscopy [18].
The integral intensities А8 of skeleton stretching vibra-
It follows from Eq. (4) that the effect of the
structure of the acyl group on ΔGij is described by the
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 6 2008

1244
RUBACHENKO et al.
of the acyl group. Therefore, the whole set of the
examined reactions can be considered as a common
reaction series. This conclusion is additionally
supported by the fact that all the examined reactions
show a good isothermodynamic correlation (see figure)
between the free energies and calculated heats1 of
reaction (1):
Table 2. IR characteristics of ν8a and ν8b vibrations of a
series of N-acyloxypyridinium tetraphenylborates (solutions
in CH3CN)
ν8a,
cm–1
ν8b,
cm–1
A8 × 10–3
,
l mol–1 cm–2
Comp. no.
Nu
Acyl
1
2
3
4
5
6
7
8
Nu2
Nu2
Nu4
Nu4
Nu5
Nu5
Nu7
Nu7
Ac1
Ac2
Ac1
Ac2
Ac1
Ac2
Ac1
Ac2
1614.0 1582.0
1613.5 1582.0
1629.0 1576.5
1628.0 1576.0
1.30
1.38
ΔG0i–9 = (–5.76 0.61) + (1.58 0.08)(–ΔН0i–9);
(5)
2.99
n 31; r 0.962; S0 3.00.
3.16
1631.0
1632.0
1642.0
1644.0
1574.5
1573.5
1573.5
1575.0
11.98
12.83
32.10
31.60
The observance of Eq. (5), in turn, suggests [19]
that the mechanism of the reactions studied is the same
and the whole reaction series follows the linear free
energy relationship [21]. The latter can be readily
verified. The experimentally measured equilibrium
constants of reaction (1) can be presented as two
equivalent reaction series consisting of 29 systems,2 in
which either the nucleophile (Nui = const = Nu9) or the
leaving group (Nuj = const = Nu9) is varied. For the
case of variation of the leaving group, we have the
following linear correlation:
tions of the ring (ν8a and ν8b, assignment according to
[19]) of a series of N-acyloxypyridinium cations are
given in Table 2. These quantities are essentially
constant in pairs of system nos. 1–2, 3–4, 5–6, and 7–
8, i.e., are independent of the structure of the acyl
group but strongly depend on the substituent in the
ring (cf. А8 for system nos. 1, 3, 5, 7 and 2, 4, 6, 8,
Table 2).
log Ki9 = (3.54 0.09) – (2.32 0.06)pKBH+
n 29, r 0.992; S0 0.23.
;
(6)
It is known [20] that the quantities А8 are
determined by the effects of n,π conjugation between
the substituent in the ring and the reaction center.
Hence, the constancy of А8 indicates that the electronic
interaction of the onium fragment of the cation and the
carbonyl carbon atom is independent of the structure
The high quality of correlation (6) is a one more
evidence of the conclusion that equilibrium of the
reactions under consideration is insensitive to the
structure of the acyl fragment of the acylonium cations
and depends only on the structure of the nucleophile
and leaving group. As seen from Eq. (4), correlation (6)
can be written in the form of an equation symmetrical
with respect to the participants of reaction (1) and
covering all possible combinations of Nui and Nuj:
ΔGij, kJ mol–1
log Kij = (0 0.11) + (2.29 0.03)(pKBH+ – pKBH+);
n 125, r 0.992; S0 0.35.
(7)
7
30
15
6
From Eq. (6) or (7), we can estimate pKBH+ for
Nu15 and Nu16: 2.06 and 3.34,3.34.an estimateinations
off an equation symmetrical with respect to the ucture
of the acyl fragment of the acyloniumelationshi
respectively.
20
5, 14, 19, 22, 25, 28, 32
10
4, 10, 18, 21, 24, 27, 31
0
13
8
9
12 11
3
17
The reaction constant (ρ 2.32) in Eqs. (6) and (7)
actually indicates that the equilibrium of the acyl
–10
–20
2, 16, 20, 23, 26, 30
1
–25 –20 –15 –10 –5
0
5
10
1
Note that the calculated heats of reaction (1) reasonably agree
with the experimental results (few in number) that we obtained
previously [17].
ΔHij, kJ mol–1
Correlation between the equilibrium constants and
calculated heats of reactions (1) (numbering of reaction
systems is the same as in Table 1).
2
We have not found in the literature the values of pKBH+ for Nu15
and Nu16. For Nu9, pKBH+ 1.43 [11].
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EQUILIBRIUM OF ACYL TRANSFER BETWEEN PYRIDINE N-OXIDES
1245
transfer is more sensitive to structural effects than the
protonation equilibrium. However, the parameters
pKBH+ of N-oxides, used in correlations (6) and (7),
were measured in water, and log Kij, in acetonitrile. Let
us take for the correlation the parameters pKBH+ of N-
oxides in СH3CN (Table 1). As a result, we obtain the
equation similar to (7):
Quantum-chemical calculations were performed by
the АМ1 method using the HyperChem 4 program
package.
1-Acetyloxy-4-(4'-N,N-dimethylaminostyryl)pyri-
dinium tetraphenylborate. 4-(4'-N,N-Dimethylamino-
styryl)pyridine N-oxide (0.075 g) was dissolved in a
small amount of acetic anhydride (~3 ml). To the
resulting solution, a fourfold excess of sodium
tetraphenylborate (~0.42 g) was added in the dark, and
the mixture was vigorously stirred for 10–15 min.
Then ~100 ml of diethyl ether was added, and after
30–40 min the precipitate (dark violet crystals) was
filtered off. Yield ~0.14 g (~80%). The salt is
photosensitive, and all manipulations with it were per-
log Kij = (0 0.18) + (1.23 0.01)(pKBH+ – pKBH+);
n 125, r 0.997; S0 0.20.
(8)
The quality of correlation of (8) is appreciably
higher than that of (7), despite the fact that many of the
values of pKBH+ in acetonitrile are calculated and not
measured. A considerably lower absolute value of the
reaction constant in (8) is apparently due to the solvent
effect. Formally the proton is the same acid residue as
Асyl in reaction (1). Therefore, closeness of ρ in Eq. (8)
to unity (1.23) clearly shows once again that the nature
of the group being transferred in acyl exchange (1)
exerts a minor influence on the reaction equilibrium.
1
formed in the red light. H NMR spectrum (200 MHz;
acetone-d6), δ, ppm (J, Hz): 8.55 d (2H, Pyα, J 7.0),
8.03 d (2H, Pyβ, J 7.0), 7.93 d (2Н, –CH=CH–, J
16.4), 7.64 d (2Н, Ph, J 8.0), 7.21 d (2Н, –CH=CH–, J
16.3), 7.34 m [8Н, BPh4– (o-H)], 7.05
d (2Н, Ph, J 8,0),
6.92 m [8Н, BPh4– (m-H)], 6.76 m [4Н, BPh4– (p-H)],
3.07 s [6Н, (CH3)2N–], 2.42 s (3Н, CH3). Found, %: С
81.8; H 6.3; N 4.4. C41H39BN2O2. Calculated, %: C
81.7; H 6.5; N 4.6.
EXPERIMENTAL
All the nucleophiles were prepared and purified as
in [11, 12]. Acetonitrile (Acros for HPLC) were kept
over 3 Å molecular sieves before use.
The other salts were prepared as in [11, 12].
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The IR spectra were recorded on a Perkin–Elmer
Spectrum BX spectrophotometer (resolution 4 cm–1).
The accuracy of determining the frequencies and
integral intensities was 0.5 cm–1 and 5%, respec-
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