Molecular energetics of alkyl substituted pyridine N-oxides: An experimental study

Article abstract of DOI:10.1007/s10973-009-0646-7

The standard (p° = 0.1 MPa) energies of combustion in oxygen, at T = 298.15 K, for the solid compounds 2-methylpyridine-N-oxide (2-MePyNO), 3-methylpyridine-N-oxide (3-MePyNO) and 3,5-dimethylpyridine-N-oxide (3,5-DMePyNO) were measured by static-bomb calorimetry, from which the respective standard molar enthalpies of formation in the condensed phase were derived. The standard molar enthalpies of sublimation, at the same temperature, were measured by Calvet microcalorimetry. From the standard molar enthalpy of formation in gaseous phase, the molar dissociation enthalpies of the N-O bonds were derived, and compared with values of the dissociation enthalpies of other N-O bonds available for other pyridine-N-oxide derivatives.

Full text of DOI:10.1007/s10973-009-0646-7

J Therm Anal Calorim (2010) 100:431–439
DOI 10.1007/s10973-009-0646-7
Molecular energetics of alkyl substituted pyridine N-oxides
An experimental study
•
Joana I. T. A. Cabral Ricardo A. R. Monteiro
•
•
Marisa A. A. Rocha Luıs M. N. B. F. Santos
•
´
William E. Acree Jr. Maria D. M. C. Ribeiro da Silva
•
Portuguese Special Chapter
Received: 17 December 2008 / Accepted: 26 March 2009 / Published online: 20 January 2010
´
´
Ó Akademiai Kiado, Budapest, Hungary 2010
Abstract The standard (p° = 0.1 MPa) energies of com-
bustion in oxygen, at T = 298.15 K, forthe solid compounds
2-methylpyridine-N-oxide (2-MePyNO), 3-methylpyridine-
N-oxide (3-MePyNO) and 3,5-dimethylpyridine-N-oxide
(3,5-DMePyNO) were measured by static-bomb calorime-
try, from which the respective standard molar enthalpies of
formation in the condensed phase were derived. The standard
molar enthalpies of sublimation, at the same temperature,
were measured by Calvet microcalorimetry. From the stan-
dard molar enthalpy of formation in gaseous phase, the molar
dissociation enthalpies of the N–O bonds were derived, and
compared with values of the dissociation enthalpies of other
N–O bonds available for other pyridine-N-oxide derivatives.
selectively on hypoxic cells of solid tumors. In this context,
formation of N-oxide derivatives has been attracting the
research interest from many viewpoints that include very
important pharmacological applications for which the basic
knowledge of chemical bonding has to be expanded [1–4].
The breaking and making of chemical bonds involved in
chemical processes justifies the need for thermochemical
data for key compounds, to provide credible correlations
between structure and energetics, from which it will be
possible to estimate data for unstudied related compounds.
In our Research Group, the molecular energetics of nitro-
gen heterocyclic compounds, with terminal N–O bonds,
has been one of our main interests during the last decade
[5], in order to derive the dissociation enthalpy of the N–O
bond, DHmo ðNꢁO). Indeed several classes of compounds
with N–O terminal bonds have been studied, with partic-
ular attention devoted to quinoxaline N,N-dioxides [5–10],
pyrazine N,N-dioxides [5, 11, 12], phenazine N,N-dioxides
[5–13], benzofurazan N-oxides [5]. The state of art con-
cerning the energetics on pyridine N-oxide derivatives is
summarized below. Shaofeng and Pilcher [14] determined
the standard molar enthalpy of formation of crystalline
Keywords N-oxide organic compounds ꢀ
Energy of combustion ꢀ Standard molar enthalpies ꢀ
Static bomb ꢀ Calorimetry ꢀ Calvet microcalorimetry
Introduction
Several of N-oxide organic compounds have shown to
undergo selective reduction under anaerobic conditions,
and are believed to be likely bioreducing agents able to act
pyridine N-oxide as DfHmo ðcr) ¼ ð8:6 ꢂ 2:3Þ kJ molꢁ1
;
using solution-reaction calorimetry, and the standard molar
enthalpy of sublimation, DgcrHmo ¼ ð79:3 ꢂ 1:0Þ kJ molꢁ1
;
by Calvet microcalorimetry. From the value of DfHmo ðg) ¼
ð87:9 ꢂ 2:5Þ kJ molꢁ1; it has been possible to derive the
J. I. T. A. Cabral ꢀ R. A. R. Monteiro ꢀ
M. A. A. Rocha ꢀ L. M. N. B. F. Santos ꢀ
M. D. M. C. Ribeiro da Silva (&)
DHmo ðNꢁO) as (301.7 2.8) kJ mol-1
. Independent
´
Centro de Investigac¸a˜o em Quımica, Department of Chemistry,
measurements by da Silva et al. [15], applying the same
method to determine the enthalpy of formation of the
crystalline compound and a Knudsen method to measure
the enthalpy of sublimation, led to a value of DHmo
ðNꢁO) ¼ ð300:0 ꢂ 1:8Þ kJ molꢁ1; in good agreement with
the one obtained by Pilcher, although a very high value
Faculty of Science, University of Porto, Rua do Campo Alegre,
687, 4169-007 Porto, Portugal
e-mail: mdsilva@fc.up.pt
W. E. Acree Jr.
Department of Chemistry, University of North Texas, Denton,
TX 76203-5070, USA
123

432
J. I. T. A. Cabral et al.
for the
a
DHmo ðNꢁO) on the class of pyridine
enthalpy of sublimation of 3-methylpyridine-N-oxide has
been estimated, due to the difficulties to perform the respec-
tive experimental measurements. These values were used to
derive the standard molar enthalpies of formation, in the
gaseous phase, of the corresponding compounds.
N-oxides. The use of combustion techniques with this
compound is very difficult, since crystalline pyridine N-
oxide is highly hygroscopic. Steele et al. [16] were able to
overcome this problem and used the combustion calorim-
etry to determine the standard molar enthalpy of formation
of pyridine N-oxide, in the condensed phase, as
(44.1 0.5) kJ mol-1. Using this value, the derived value
of the bond enthalpy of dissociation is DHmo ðNꢁOÞ ¼
ð266:2 ꢂ 2:0Þ kJ molꢁ1; an acceptable value [5], showing
that the reaction-solution calorimetric result was in error by
The compound 2-methylpyridine-N-oxide has a very low
melting point (T = 322.95 K, [22]), and it can continue in a
metastable liquid phase, without crystallizing for a long
period, when it is cooled under the melting temperature.
For that we decided to measure vapor pressure of this
compound, using a static apparatus based on a capacitance
diaphragm gauge.
&36 kJ mol-1
.
Airoldi and Gonc¸alves [17], using solution-reaction calo-
rimetry, determined the standard molar enthalpies of forma-
tion of crystalline 2-, 3-, and 4-methylpyridine-N-oxides as,
respectively (10.3 0.8) kJ mol-1, (8.8 0.7) kJ mol-1
From the standard molar enthalpies of formation in the
gaseous phase of the three alkylpyridine N-oxide deriva-
tives studied and from the standard molar enthalpies of
formation in gaseous phase of the three the corresponding
alkylpyridine derivatives, the molar dissociation enthalpies
of the N–O bonds were derived. Comparisons were made
with values in other pyridine-N-oxide derivatives.
and (12.9 0.9) kJ mol-1
.
This last compound,
4-methylpyridine-N-oxide, was also studied by Lebedev [18]
applying combustion calorimetry techniques, obtaining the
value DfHmo ðcr) ¼ ꢁð0:5 ꢂ 2Þ kJ molꢁ1: Independent mea-
surements by combustion calorimetry carried out in our
Research Group, yielded a value for the standard molar
enthalpies of formation of crystalline ꢁ41-methylpyridine-N-
oxide, DfHmo ðcr) ¼ ð5:6 ꢂ 2:1Þ kJ mol [19], which is not
in agreement neither with the values measured by Lebedev
et al. [18] or by Airoldi and Gonc¸alves [17].
Experimental
Synthesis of materials and purity control
The systematic study of pyridine N-oxide derivatives by
our Research Group was extended to numerous other com-
pounds such as nitro [19, 20], carboxy [19, 20], hydroxyl [19],
cyano[19], and carboxamide pyridine N–O derivates [21].
Besides our interest on the values of the gaseous
enthalpies of formation of the pyridine N-oxides, we have
been investigating the effect of the chemical environment
of the nitrogen heterocycle N-oxides, on the dissociation
enthalpy of the terminal (N–O) bond.
The 2-MePyNO (Acros Organics, 98%) and 3-MePyNO
(Aldrich, 98%) were purchased from commercial sources
and submitted to purification by fractional distillation under
reduced pressure. 3,5-DMePyNO was prepared by the per-
oxyacetic acid oxidation of 3,5-dimethylpyridine according
to the published synthetic procedure of Essery and Schofield
[23]. 3,5-Dimethylpyridine and 30% hydrogen peroxide
were dissolved in acetic acid, and the resulting mixture was
heated at 343–353 K for 12 h, with additional 30% of
hydrogen peroxide being added at the 3-h mark. The reaction
mixture was then cooled and basified with sodium hydroxide
solution. The product was extracted into chloroform, dried
over anhydrous sodium carbonate, and then distilled under
reduced pressure. The experimentally determined mass
fractions for 3,5-DMePyNO were in agreement with the
expected values for C7H9NO: found: C, 0.6821; H, 0.0744;
N, 0.1131; calculated: C, 0.6827; H, 0.0737; N, 0.1137.
As the compounds have shown to be hygroscopic, before
the combustion experiments they were dried and handled
under dry nitrogen atmosphere. However, a small amount of
water was absorbed when they were handled during the
experiments, as shown by the CO2 recoveries from the
combustions. The absence of other impurities than water
was confirmed by GLC. The average ratios of the mass
of carbon dioxide recovered after the combustion to those
calculated from the mass of sample were: for 2-MePyNO
(0.99672 0.00053), for 3-MepyNO (0.99910 0.00005
In the present paper, the standard (p° = 0.1 MPa) molar
enthalpies of formation, at T = 298.15 K, for three pyridine
N-oxide derivatives (2-methylpyridine-N-oxide, 2-MePyNO;
3-methylpyridine-N-oxide, 3-MePyNO, and 3,5-dimethyl-
pyridine-N-oxide, 3,5-DMePyNO) (Fig. 1), were derived
from static-bomb calorimetry. The enthalpies of sublimation
of 2-methylpyridine-N-oxide and 3,5-dimethylpyridine-
N-oxide were measured by Calvet microcalorimetry; the
O–
N+
O–
N+
O–
N+
CH3
CH3
H3C
CH3
A
B
C
Fig. 1 Structural formula for 2-MepyNO (a), 3-MePyNO (b), and
3,5-DMPyNO (c)
123

Molecular energetics of alkyl substituted pyridine N-oxides
433
and for 3,5-DMeNO (0.99200 0.00005) with the uncer-
tainties being the standard deviations of the mean.
from washing the inside of the bomb. If a small amount of
carbon was formed inside the crucible, its amount was deter-
mined by weight and taken into account for the calculation of
the massic energy of combustion.
Combustion calorimetry
The standard massic energies of combustion of the
compounds studied experimentally, i.e., 2-MePyNO,
3-MePYNO, and 3,5-DMePyNO, all in the solid phase, were
measured by static-bomb combustion calorimetry, using
two different isoperibol static-bomb calorimeters: Calo-
rimeter 1 for 2-MePyNO and Calorimeter 2 for the other two
compounds. In the experiments performed with Calorimeter
1, a twin valve bomb, model 1105 (Parr Instrument, IL,
USA) of internal volume 0.340 cm3 was used. A detailed
description of the apparatus and the technique can be found
in the literature [24, 25]. The bomb used with Calorimeter 2
has an internal volume of 0.290 cm3 and the description of
this combustion calorimeter can also be found in literature
[26–28]. Both calorimeters were calibrated by combustion
of thermochemical standard benzoic acid, sample NBS 39j,
with Dcu ¼ ꢁð26434 ꢂ 3Þ J gꢁ1 [29], under experimental
Calvet Microcalorimetry
The standard molar enthalpies of sublimation of 2-MePyNO
and 3,5-DMePyNO were measured by Calvet High Tem-
perature Microcalorimetry using a similar technique to that
described by Skinner and Snelson [32]. Samples about
3–5 mg contained in a thin glass capillary tube were drop-
ped at the room temperature, into the hot reaction vessel, in a
high temperature Calvet microcalorimeter (SETARAM HT
1000D) held at T = 355 K for 2-MePyNO and at T = 371 K
for 3,5-DMePyNO, and then removed from the hot zone by
vacuum sublimation. The observed enthalpies of subli-
mation were corrected to T = 298.15 K, using DT298:15KHmo
(g) estimated by a group method based on the values
from Stull et al. [33]. The microcalorimeters were calibrated
in situ for the working temperatures with naphthalene
(DgcrHmo ðnaphthalene; crÞ ¼ ð72:60 ꢂ 0:60Þ kJ molꢁ1 [34])
using the same procedure for the calibration experiments.
conditions, and found to be ecal = (15917.4 1.4) J K-1
,
for Calorimeter 1, and ecal = (15553.3 0.9) J K-1, for
Calorimeter 2. The calibrations followed the procedure
previously described [30], and the results were corrected to
give the energy equivalents, ecal, corresponding to the
average mass of water added to the calorimeters of 3119.6
and 2900 g, respectively, for Calorimeter 1 and Calorimeter
2. The uncertainties quoted are the standard deviations of the
mean, of at least 6 experiments for Calorimeter 1 and 11 for
Calorimeter 2.
Vapor pressure measurements
As the compound 2-methylpyridine-N-oxide has low
melting point and it remains in the liquid state for a long
period, without crystallizing, it was decided to measure the
vapor pressures of this compound, at different tempera-
tures, using a static apparatus based on a capacitance dia-
phragm gauge. The apparatus, the measuring procedure
and the results obtained from the vapor pressure mea-
surements of recommended reference materials (naphtha-
lene, benzoic acid, benzophenone and ferrocene) have been
described in the literature [35].
The solid compounds were pressed into pellet form. As
they have shown to be hygroscopic, the pellets were burnt
enclosed in sealed Melinex bags, with 0.025 mm of
thickness and a massic energy of combustion of Dcuo ¼
ꢁð22902 ꢂ 5Þ J gꢁ1 [31], corrected for the mass fraction of
water w = 0.0032 [31].
The pressure is measured by a capacitance diaphragm
absolute gauge MKS Baratron 631A11TBFP. This sensor is
capable of measuring in the pressure range of [5–1333] Pa
and in the temperature range of [253–473] K, with an
accuracy better than 0.5% of the reading pressure, as stated
by the manufacturer. To avoid condensation of the sample,
the temperature of the vacuum line was maintained 10–20 K
above the sample temperature and the pressure sensor dia-
phragm is self controlled at T = 473 K.
All substances were burnt in an oxygen atmosphere, with
1.00 cm3 of water added to the bomb, at an initial pressure
of 3.04 MPa, after purging the bomb twice with oxygen to
remove the air. The calorimetric temperatures were mea-
sured at time intervals of 10 s, and at least 100 readings were
taken for each the fore, the main and the after periods. The
ignition was made at T = (298.150 0.001) K, by the
discharge of a 1400 lF capacitor through the platinum
ignition wire. A cotton-thread fuse with empirical formula
of CH1.686O0.843 was used, with a massic energy of com-
bustion of ꢁDcuo ¼ 16240 J gꢁ1 [30]. At the end of each
combustion experiment, the amount of compound burnt in
that experiment was determined from the total mass of CO2
produced, taking into account that formed from cotton-
thread fuse and from Melinex. The amount of HNO3 formed
was determined by titration of the aqueous solution resulting
Experimental results
Results for a typical combustion experiment of each
compound are given in Table 1, where Dm(H2O) is the
deviation of the mass of water added to the calorimeter
123

434
J. I. T. A. Cabral et al.
Table 1 Results of a typical combustion experiment, at T = 298.15 K
Table 2 Individual values of the massic energy of combustion,Dcuo,
for the compounds, at T = 298.15 K
Experiment
2-MePyNO
3-MePyNO
3,5-DMePyNO
2-MePyNO
3-MePyNO
3,5-DMePyNO
m (CO2, total)/g
m (cpd)/g
1.08916
0.41168
0.03817
0.00345
0.85702
15.46
2.37025
0.88856
0.09753
0.00256
1.90908
15.14
2.01950
0.80575
–
ꢁ1
ꢁDcuo= J g
30814.30
30778.57
30787.61
30784.90
30797.12
30780.26
30846.98
30794.12
30856.17
30858.57
30803.28
30841.94
30820.33
32488.60
32541.44
32551.53
32553.29
32538.94
32522.37
32539.42
m (melinex)/g
m (fuse)/g
0.00242
1.69000
15.00
-3.1
DTad= K
ef= J Kꢁ1
Dm (H2O)/g
-DU (IBP)a/J
DU (melinex)/J
DU (fuse)/J
DU (HNO3)/J
DU (ign)/J
0.0
-2.6
13654.04
874.27
56.03
29699.44
2233.53
41.57
26287.36
–
ꢁhDcuoi=ðJ g
30790.5 5.5
Þ
ꢁ1
39.30
55.15
1.15
30831.6 9.8
32533.7 8.5
29.79
61.29
0.74
1.19
masses used were those recommended by the IUPAC
Commission in 2005 [39]. For all compounds studied, the
individual values of Dcuo, together with the means and their
standard deviations, are given in Table 2.
DU (Carbon)/J
–
66.0
–
DUR/J
ꢁDcuo=J gꢁ1
8.32
19.66
15.22
32488.60
30814.30
30846.98
m(CO2, total) is the total mass of carbon dioxide recovered in the
combustion; m(cpd) is the mass of compound burnt in each experi-
ment; m(melinex) is the mass of Melinex used to enclose the com-
pounds; m(fuse) is the mass of the cotton-thread fuse; DTad is de
adiabatic temperature rise; efis the energy equivalent of the calo-
rimeter including the contents of the bomb in the final state; Dm(H2O)
is the deviation of the mass of water added to the calorimeter from
3119.6 g (calorimeter 1) or 2900.0 g (calorimeter 2); DU(IBP) is the
energy change for isothermal combustion reaction under actual bomb
conditions; DU(melinex) is the energy of combustion of the melinex
used in each experiment; DU(fuse) is the energy of combustion of the
fuse (cotton); DU(HNO3) is the energy correction for the nitric acid
formation; DU(ign) is the electrical energy supplied for ignition,
DU(carbon) is the energy correction for the carbon residue soot for-
mation; DURis the standard state correction; Dcuo is the massic energy
of combustion of the compound
Table 3 lists, for each compound, the derived values for
the standard molar energy (DcUmo ) and enthalpy (DcHmo ) of
combustion and the standard molar enthalpy of formation,
DfHmo , in the condensed phase. The uncertainties of the
standard molar energies and enthalpies of combustion are
twice the final overall standard deviation of the mean, and
include the uncertainties in calibration [40, 41] as well as
the respective uncertainties of the auxiliary compounds
used.
The values of the standard molar enthalpies of formation in
the condensed phase, at T = 298.15 K, DfHmo (cr), were
derived from DcHmo , using the values of the standard molar
enthalpies of formation of liquid water and gaseous car-
bon dioxide, respectively, DfHmo ðH2O; l) ¼ ꢁð285:830 ꢂ
0:042Þ kJ molꢁ1 [42] and DfHmo ðCO2; g) ¼ ꢁð393:51 ꢂ
0:13Þ kJ molꢁ1 [42].
a
DU(IBP) already includes DU(ign)
from 3119.6 g (calorimeter 1) or from 2900.0 g (calorim-
eter 2), with the internal energy for the isothermal bomb
process, DUIBP, calculated according to the Eq. 1.
Results of the microcalorimetric determinations of the
enthalpy of sublimation of 2-MePyNO and 3,5-DMePyNO,
are given in the Table 4. The values of the enthalpies of
sublimation, at the experimental temperature T, correspond
to the mean values of six independent experiments with the
uncertainties given by their standard deviations. The
observed molar enthalpies of sublimation,Dgcr;T;298:15KHm,
were corrected to T = 298.15 K using DT298:15KHmo (g) esti-
mated by a group scheme based on the values of Stull
et al. [33]. The schemes applied for these corrections are:
2-MePyNO = 2-MePy ? NO and 3,5-DMePyNO = 2 9
3-MePy - Py ? NO, which gives, at T = 355.4 K,
D235985::14K5KHmo ð2 - MePyNO) ¼ 7:20 kJ molꢁ1 and at Tꢁ=1
DUIBP ¼ ꢁfecal þ DmH OcpðH2O; l) þ efgDTad
2
þ DUignition
:
ð1Þ
DU(fuse) is the energy of combustion of the cotton-thread
fuse and DU(melinex) the energy of combustion of the
melinex used in the experiments. The corrections for nitric
acid formation, DU(HNO3), were based on -59.7 kJ mol-1
,
for the molar energy of formation of 0.1 mol dm-3
HNO3(aq), from N2 (g), O2 (g) and H2O (l) [36] and DU(ign)
is the electrical energy supplied for ignition. For each
compound, the estimated pressure coefficient of massic
energy, (qu/qp)T, at T = 298.15 K, was assumed to be
-0.2 J g-1 MPa-1, a typical value for most organic com-
pounds [37]. The correction to the standard state, DUR, and
the massic energy of combustion, Dcuo, were calculated by
the procedure of Hubbard et al. [38]. The relative atomic
371.0 K, D371:0K
298:15KHmo ð3; 5 - DMePyNOÞ ¼ 11:32 kJ mol
:
The uncertainties associated to the standard molar enthal-
pies or sublimation, at T = 298.15 K, are twice the standard
deviation of the mean and include the uncertainty associated
with the calibration procedure.
123

Molecular energetics of alkyl substituted pyridine N-oxides
435
Table 3 Derived standard (p° = 0.1 MPa) molar energies of combustion, DcUmo , standard molar enthalpies of combustion, DcHmo , and standard
molar enthalpies of formation for the compounds in the condensed phase, DfHmo (cr), at T = 298.15 K
Compound
ꢁDcUmo =kJ molꢁ1
ꢁDcHmo =kJ molꢁ1
DfHmo ðcr)/kJ molꢁ1
2-MePyNO (cr)
3-MePyNO (cr)
3,5-DMePyNO (cr)
3360.0 1.6
3364.5 2.2
4006.6 2.2
3361.9 1.6
3366.4 2.3
4009.7 2.2
0.4 1.8
4.9 2.4
-31.1 2.4
Table 4 Microcalorimetric standard (p°= 0.1 MPa) molar enthalpies of sublimation, at T = 298.15 K
Compound
Number of
experiments
T/K
Dgcr;T;298:15KHm=kJ molꢁ1
DT298:15KHmo ðg)/ kJ molꢁ1
DgcrHmo ðT ¼ 298:15KÞ=kJ molꢁ1
2-MePyNO (cr)
6
6
355.4
371.0
100.07 0.50
112.2 1.2
7.20
92.9 1.9
3,5-DMePyNO (cr)
11.32
100.9 2.3
experimental data were fitted by the Clarke and Glew
equation [43].
Table 5 Derived standard (p° = 0.1 MPa) molar enthalpies of
formation, DfHmo , and of sublimation, DcgrHmo , at T = 298.15 K
ꢀ
ꢁ
ꢀ
ꢁ
Compound
DfHmo ðcr)/
DgcrHmo =
DfHmo ðg)/
p
po
Dgl Gom
1
1
kJ molꢁ1
kJ molꢁ1
kJ molꢁ1
R ꢀ ln
¼ ꢁ
þ Dgl Hmo ðhÞ ꢃ
ꢁ
h
h
T
ꢂꢀ ꢁ
ꢀ ꢁꢃ
h
T
þ Dgl Cpo;mðhÞ
ꢁ 1 þ ln
ð2Þ
2-MePyNO
0.4 1.8
92.9 1.9
[91 6]a
93.3 2.6
95.9 6.4
69.8 3.3
T
h
3-MePyNO
4.9 2.3
where p is the vapor pressure, po is a selected reference
pressure, h is a selected reference temperature, and R is the
molar gas constant (R = 8.314472 J K-1 mol-1), DlgGmo is
the standard molar Gibbs energy of vaporization at the
selected reference pressure (the gaseous phase is supposed
to have characteristics of an ideal gas at the pressure po),
3,5-DMePyNO
-31.1 2.4
100.9 2.3
aEstimated from literature values for the pyridine isomers [44]
The values of the standard molar enthalpies of formation
in the condensed state, together with the ones of the
enthalpies of sublimation, yield the standard molar
enthalpies of formation of the studied compounds in the
gaseous state, which are registered in Table 5.
Table 7 Parameters of Clarke and Glew equation for 2-MePyNO (l)
at the reference temperature T = 298.15 K and pressure p° = 105 Pa
The vapor pressure of 2-MePyNO was measured in the
liquid state. The experimental data of the vapor pressure
for the studied compound are listed in Table 6. The
Compound
Dgl Gom/J mol-1
Dgl Hmo /J mol-1
2-MePyNO (l)
21334 63
54333 488
DlgCpo;m ¼ ꢁ100J Kꢁ1 molꢁ1
Table 6 Experimental data of vapor pressure for 2-MePyNO in
liquid state
6.4
6.2
6.0
5.8
5.6
5.4
5.2
5.0
4.8
T/K
p/Pa
Dpa/Pa
2-MePyNO (l)
328.64
331.63
334.60
337.59
340.56
343.55
346.52
349.51
352.49
355.46
a
134.5
157.5
184.7
211.3
251.7
295.6
338.6
394.6
465.2
530.2
2.2
0.9
0.2
-5.4
-1.5
0.3
-4.2
-2.2
7.5
2.80
2.85
2.90
2.95
3.00
3.05
1000/T (K)
4.3
Fig. 2 Plot of ln(p/Pa) versus 1/T (K) for the experimental data of
vapor pressure for 2-methylpyridine-N-oxide in liquid state. aFrom
Dp = p - pcalc, where pcalc is calculated from the Clarke and Glew
equation
b
[44], from [5], and this work
123

436
J. I. T. A. Cabral et al.
Table 8 Comparison of the mean bond dissociation enthalpies derived in this work with others reported in the literature
DfHmo ðg)=kJ molꢁ1
DfHmo ðg)/kJ molꢁ1
DHmo ðNꢁOÞ=kJ molꢁ1
Py
140.4 0.7a
99.2 0.7a
106.5 0.6a
72.0 0.9a
c
PyNO
124.7 1.9b
93.3 2.6c
95.9 6.4c
69.8 3.3c
264.9 2.0
255.1 2.7
259.8 6.5
251.4 3.4
2-MePy
3-MePy
3,5-DMePy
2-MePyNO
3-MePyNO
3,5-DMePyNO
aFrom [44], from [5], and this work
b
Dgl Hmo is the standard molar enthalpy of vaporization and
Dgl Cpo;m is the difference between the heat capacities of the
ideal gas and the liquid phase. In this work was considered
for reference temperature h = 298.15 K and standard
pressure po = 105 Pa.
vapor pressure measurements was defined by indication of
traces of decomposition of the sample at temperatures
above 360 K. Due to the short temperature interval, Dgl Cpo;m
was not derived directly from the fitting, being taken as
-100 J K-1 mol-1 and used in the fitting. With the enthalpy
of sublimation measured by high Calvet microcalorimetry
and the enthalpy of vaporization measured by the capacitance
diaphragm, it is calculated a value of (38.6 2.0) kJꢀmol-1
for the fusion enthalpy of 2-MePyNO.
The parameters of the Clarke and Glew equation (Eq. 2)
are presented in Table 7, and the experimental vapor
pressure measurements and the predicted data from the
fitted equation are shown in Fig. 2. The upper limit of the
Scheme 1 Enthalpic effect due
to substitution of methyl groups
in Pyridine and Pyridine-N-
N
CH3
oxide (all values in kJ mol-1).
a
b
From [44], from [5], this
c
−[41.2 1.0]
work
[99.2 0.7]a
N
N
−[68.4 1.1]
(34.2 kJ mol–1 per CH3)
.
H3C
CH3
[140.4 0.7]a
[72.0 0.9]a
N
−[33.9 0.9]
CH3
[106.5 0.6]a
O–
N+
CH3
O–
N+
O–
−
[31.4 3.2]
[93.3 2.6]c
N+
−
[54.9 3.8]
.
(27.4 kJ mol–1 per CH3)
O–
N+
H3C
CH3
[69.8 3.3]c
[124.7 1.9]b
−
[28.8 6.7]
CH3
[95.9 6.4]c
123

Molecular energetics of alkyl substituted pyridine N-oxides
437
Scheme 2 Enthalpic effect due
to substitution of methyl groups
in Pyrazine and Pyrazine
CH3
N
N,N-dioxide (all values in
c
−
[70.1]
a
b
kJ mol-1). [46], [47], [48],
N
[126]a
e
d[11], and [12]
N
CH3
CH3
N
CH3
H3C
H3C
−[141.4 4.7]
–1
.
(35.4 kJ mol per CH3)
N
N
CH3
N
−[80.2 2.6]
[54.7 4.5]a
[196.1 1.3]b
N
H3C
[115.9 2.3]e
O–
N+
CH3
CH3
O–
N+
O–
N+
−
[94.2 4.2]
N+
CH3
H3C
H3C
O–
[92.3 3.8]e
−
[185.5 3.9]
.
O–
N+
(46.2 kJ mol–1 per CH3)
N+
N+
CH3
CH3
−[87.9 4.0]
O–
O–
[1.0 3.4]d
[186.5 1.9]c
N+
H3C
O–
[98.6 3.5]e
Discussion
and 3,5-DMePy, respectively, and DfHmo ðO; g) ¼ ð249:18 ꢂ
0:10Þ kJ molꢁ1 [42], according to the gaseous reaction,
X-PyNO ? X-Py ? O, where X = 2-Me, 3-Me, or 3,5-
DMe. These values are summarized in Table 8. The analysis
of the values of DHmo ðNꢁO) calculated for the studied
compounds, allows us to conclude that the presence of the
substituting groups in pyridine molecule does not induce
significant effects in the N–O bond, since the values remain
fairly constant and within the expected interval of (260
10) kJ mol-1 [5]. None of the three methylpyridine-N-oxide
derivatives studied here have a functional group in the 2- and/
or 6-ring position capable of hydrogen bond formation with
the oxygen atom of the N-oxide group. Except for three
pyridinecarboxiamide N-oxides [21], the pyridine N-oxides
having DHmo ðNꢁOÞ values outside of the (260 10)
kJ mol-1 interval have had either a –COOH [19] or –OH [45]
functional group in the 2-position.
The standard molar enthalpy of formation, in condensed phase,
for 2-MePyNO and 3-MePyNO have already been published
by Airoldi and Gonc¸alves [17], measured by reaction-solution
calorimetry, as DfHmo (2-MePyNO, cr) = (10.5 0.8) kJ
mol-1 and DfHmo (3-MePyNO, cr) = (8.8
0.7) kJ mol-1
.
These values are somewhat different from those obtained in this
work: DfHmo ð2-MePyNO; cr) ¼ ð0:4 ꢂ 1:7Þ kJ molꢁ1 and
DfHmo ð3-MePyNO; cr) ¼ ð5:0 ꢂ 2:3Þ kJ molꢁ1
.
Since the compounds under study are extremely
hygroscopic, its handling is very difficult, so it was
impossible to determine experimentally the standard molar
enthalpy of sublimation for 3-MePyNO. This was esti-
mated based on literature [44] values of the pyridine
isomers.
The standard molar enthalpies of dissociation of the
N–O bond, DHmo ðNꢁO), on 2-MePyNO, 3-MePyNO, and
3,5-DMePyNO were derived from the values of the stan-
dard molar enthalpies of formation, in gaseous phase, of
those N-oxide alkylderivatives and of 2-MePy, 3-MePy,
Scheme 1 presents the comparison of the enthalpic
increments due to the introduction of methyl groups in
positions 2-, 3- and 3,5- in Py and PyNO. The effect of
stabilization due to the introduction of methyl groups
123

438
J. I. T. A. Cabral et al.
7. Gomes JRB, Ribeiro da Silva MDMC, Ribeiro da Silva MAV.
Quinoxaline-1,4-dioxide: substituent effects on the N–O bond
dissociation enthalpy. Chem Phys Lett. 2006;429:18–22.
8. Gomes JRB, Sousa EA, Gomes P, Vale N, Gonc¸alves JM, Pandey
S, et al. Thermochemical studies on 3-methyl-quinoxaline-2-
carboxamide-1,4-dioxide derivatives: enthalpies of formation and
of N–O bond dissociation. J Phys Chem B. 2007;111:2075–80.
9. Gomes JRB, Sousa EA, Gonc¸alves JM, Gales L, Damas AM,
Gomes P, et al. Energetic and structural characterization of 2-R-
3-methylquinoxaline-1,4-dioxides (R = benzoyl or tert-butoxy-
carbonyl): experimental and computational studies. J Phys Org
Chem. 2007;20:491–8.
10. Gomes JRB, Monteiro AR, Campos BB, Gomes P, Ribeiro da
Silva MDMC. The enthalpies of dissociation of the NO bonds in
two quinoxaline derivatives. J Phys Org Chem. 2009;22:17–23.
11. Ribeiro da Silva MDMC, Vieira MAA, Givens C, Keown S, Acree
WE Jr. Experimental thermochemical study of two polymethyl-
pyrazine N,N0-dioxide derivatives. Thermochim Acta. 2006;450:
67–70.
12. Ribeiro da Silva MDMC, Cabral JITA, Givens C, Keown S,
Acree WE Jr. Thermochemical study of three dimethylpyrazine
derivatives. J Therm Anal Calor. 2008;92:73–8.
13. Gomes JRB, Sousa EA, Gonc¸alves JM, Monte MJS, Gomes P,
Pandey S, et al. Energetics of the N–O Bonds in 2-hydroxy-
phenazine-di-N-oxide. J Phys Chem B. 2005;109:16188–95.
14. Shaofeng L, Pilcher G. Enthalpy of formation of pyridine-N-
oxide: the dissociation enthalpy of the (N–O) bond. J Chem
Thermodyn. 1988;20:463–5.
observed in Py is slightly superior than in PyNO. This
tendency in stabilization is even more evident for the
substitution in position 2- of Py, probably due to stereo-
chemical interactions between the methyl group and the
oxygen in PyNO.
It is interesting also to analyse Scheme 2, where the
enthalpic increments due to the introduction of methyl
groups in positions 2- and 3-, 2- and 5-, or 2-, 3-, 5-, and
6- in pyrazine (Pz) are compared with those in pyrazine
N,N-dioxide (PzDNO). For 2,3-DMePz may be considered
that each CH3 group is in an ortho position relatively to a
nitrogen atom, resulting in a lower stabilization than in
pyridine. On the other hand, for 2,5-DMePz may be con-
sidered that each CH3 group is in an ortho position or in a
meta position relatively to a nitrogen atom, resulting a
stabilization similar to that in 2-methylpyridine. Identical
comments may be done for the compound 2,3,5,6-TMePz,
where the stabilization for each CH3 group is identical to
that in 2,3-DMePz. In what concerns the stabilization
energy for methyl substitutions in the ring PzDNO, that is
higher than in PyNO ring, resulting in a tendency to a
decrease of the dissociation enthalpy of the N–O bond in
pyridine oxides, comparatively with the average of the
dissociation enthalpy of that bond in pyrazine N,N-dioxide
derivatives.
15. da Silva MLCP, Chagas AP, Airoldi C. Heterocyclic N-oxide
ligands: a thermochemical study of adducts with zinc, cadmium,
and mercury chlorides. J Chem Soc Dalton Trans 1988:2113–6.
16. Steele WV, Chirico DR, Collier WB, Hossenlopp JA, Nguyen A,
Strube MM. Thermochemical and thermophysical properties of
organic nitrogen compounds found in fossil fuels. NIPER-188.
DOE Fossil Energy, Bartlesville Project Office; 1986.
17. Airoldi C, Gonc¸alves L. Standard molar enthalpies of formation of
some crystalline amine N-oxides. Thermochim Acta. 1992;194:
259–63.
ˆ
Acknowledgements Thanks are due to Fundac¸a˜o para a Ciencia e
Tecnologia (FCT), Lisbon, Portugal and to FEDER for financial
support. J I.T.A.C. thanks FCT and the European Social Fund (ESF)
under Community Support Framework (CSF) for the award of a Post-
Doc research grant (BPD/27140/2006).
18. Lebdev VP, Chironov VV, Kizin AN, Falyakhov IF, Saifullin IS,
Klyuchnikov OR, et al. Izv Akad Nauk Ser Khim. 1995;4:660.
19. Ribeiro da Silva MDMC, Matos MAR, Vaz MC, Santos LMNBF,
Pilcher G, Acree WE Jr, et al. Enthalpies of combustion of the
pyridine N-oxide derivatives: 4-methyl-, 3-cyano-, 4-cyano-,
3-hydroxy-, 2-carboxy-, 4-carboxy-, and 3-methyl-4-nitro, and of
the pyridine derivatives: 2-carboxy-, and 4-carboxy-. The disso-
ciation enthalpies of the N–O bonds. J Chem Thermodyn. 1998;30:
869–78.
20. Acree WE Jr, Tucher SA, Ribeiro da Silva MDMC, Matos MAR,
Gonc¸alves JM, Ribeiro da Silva MAV, et al. Enthalpies of com-
bustion of 4-nitropyridine N-oxide and pyridine-3-carboxylic acid
N-oxide: the dissociation enthalpies of the N–O bonds in pyridine
N-oxide derivatives. J Chem Thermodyn. 1995;27:391–8.
21. Ribeiro da Silva MDMC, Gonc¸alves JM, Ferreira SCC, Da Silva
LCM, Sottomayor MJ, Pilcher G, et al. Experimental thermo-
chemical study of the enthalpies of formation and sublimation of
isonicotinamide, picolinamide, nicotinamide, isonicotinamide
N-oxide, and nicotinamide N-oxide. The dissociation enthalpies
of the N–O bonds. J Chem Thermodyn. 2001;33:1263–75.
22. Casteel JF, Sears PG. Dielectric constants, viscosities, and related
physical properties of four liquid pyridine-N-oxides at several
temperatures. J Chem Eng Data. 1974;19:303–6.
References
´
´
´
´
´
´
1. Skalova L, Nobilis M, Szotakova B, Wsol V, Kubıcek V, Bali-
harova V, et al. Effect of substituents on microsomal reduction of
´
benzo(c)fluorene N-oxides. J Chem Biol Interact. 2000;126:
185–200.
2. Greer ML, Duncan JR, Duff JL, Blackstock SC. Solid-state
complexes of quinoxaline- and phenazine-N,N0-dioxide donors
with tetracyanoethylene. Crystal engineering via donor-acceptor
interactions. Tetrahedron Lett. 1997;38:7665–8.
´
3. Ortega MA, Morancho MJ, Martınez-Crespo FJ, Sainz Y,
Montoya ME, Cerain AL, et al. New quinoxalinecarbonitrile
´
1,4-di-N-oxide derivatives as hypoxic-cytotoxic agents. Eur J
Med Chem. 2000;35:21–30.
4. Ganley B, Chowdhury G, Bhansali J, Daniels JD, Gates KS.
Redox-activated, hypoxia-selective DNA cleavage by quinoxa-
line 1,4-di-N-oxide. Bioinorg Med Chem. 2001;9:2395–401.
5. Acree WE Jr, Pilcher G, Ribeiro da Silva MDMC. The Disso-
ciation Enthalpies of Terminal (N–O) Bonds in Organic Com-
pounds. J Phys Chem Ref Data 2005;34:553–72, and references
cited therein.
23. Essery JM, Schofield K. Some derivatives of 4-amino- and
4-nitro-pyridine. J Chem Soc 1960:4953–9.
24. Ribeiro da Silva MAV, Ribeiro da Silva MDMC, Pilcher G. The
construction, calibration and use of a new high-precision static-
´
bomb calorimeter. Rev Port Quım. 1984;26:163–72.
6. Gomes JRB, Vieira MAA, Stovall DM, Acree WE Jr, Ribeiro da
Silva MDMC. Experimental thermochemical study of 6-Chloro-
2,3-dimethylquinoxaline 1,4-dioxide and DFT evaluation of the
N–O bond enthalpies in related haloquinoxalines. Bull Chem Soc
Japan. 2007;80:1770–5.
123

Molecular energetics of alkyl substituted pyridine N-oxides
439
25. Ribeiro da Silva MAV, Ribeiro da Silva MDMC, Pilcher G.
Enthalpies of combustion of 1,2-dihydroxybenzene and of six
alkylsubstituted 1,2-dihydroxybenzenes. J Chem Thermodyn.
1984; 16:1149–55.
26. Gundry HA, Harrop D, Head AJ, Lewis GB. Thermodynamic
properties of organic oxygen compounds 21. Enthalpies of
combustion of benzoic acid, pentan-1-ol, octan-1-ol, and hexad-
ecan-1-ol. J Chem Thermodyn. 1969;1:321–32.
37. Washburn EW. Standard states for bomb calorimetry. J Res Nat
Bur Stand (US). 1933;10:525–58.
38. Hubbard WN, Scott DW, Waddington G. Standard states and
corrections for combustions in a bomb at constant volume.
In: Rossini FD, editor. Experimental thermochemistry, vol. 1.
New York: Interscience; 1956.
39. Wieser ME. Atomic weights of the elements 2005 (IUPAC
Technical Report). Pure Appl Chem. 2006;78:2051–66.
40. Rossini FD. Assignment of uncertainties to thermochemical data.
In: Rossini FD, editor. Experimental thermochemistry, vol. 1.
New York: Interscience; 1956.
27. Bickerton J, Pilcher G, Al-Takhin G. Enthalpies of combustion of
the three aminopyridines and the three cyanopyridines. J Chem
Thermodyn. 1984;16:373–8.
˚
28. Ribeiro da Silva MDMC, Santos LMNBF, Silva ALR, Fernandes
´
O, Acree WE. Energetics of 6-methoxyquinoline and 6-meth-
41. Olofsson G. Assignment of uncertainties. In: Sunner S, Mansson
M, editors. Combustion calorimetry. Oxford: Pergamon; 1979.
42. Cox JD, Wagman DD, Medvedev VA. CODATA key values for
thermodynamics. New York: Hemisphere; 1989
oxyquinoline N-oxide: the dissociation enthalpy of the (N–O)
bond. J Chem Thermodyn. 2003;35:1093–100.
29. Certificate of Analysis Standard Reference Material 39j Benzoic
Acid Calorimetric Standard. Washington: NBS; 1995.
30. Coops J, Jessup RS, van Nes K. Calibration of calorimeters for
reactions in a bomba at constant volume. In: Rossini FD, editor.
Experimental thermochemistry, vol. 1. New York: Interscience;
1956.
31. Skinner HA, Snelson A. The heats of combustion of the four
isomeric butyl alcohols. Trans Faraday Soc. 1960;56:1776–83.
32. Adedeji FA, Brown DLS, Connor JA, Leung M, Paz-Andrade
MI, Skinner HA. Thermochemistry of arene chromium tricarbo-
nyls and the strenghts of arene-chromium bonds. J Organomet
Chem. 1975;97:221–8.
43. Clarke ECW, Glew DN. Evaluation of thermodynamic functions
from equilibrium constants. Trans Faraday Soc. 1966;62:539–47.
44. Pedley JB. Thermochemical data and structures of organic
compounds. Thermodynamics Research Center, College Station,
TX: CRC Press; 1994.
45. Ribeiro da Silva MDMC, Matos MAR, Miranda MS, Morais
VMF, Acree WE. Experimental and theoretical study of the
dissociation enthalpy of the N–O bond on 2-hydroxypyridine
N-oxide: theoretical analysis of the energetics of the N–O bond
for hydroxypyrydine N-oxide isomers. J Chem Thermodyn. 2004;
36:107–13.
46. Ribeiro da Silva MAV, Morais VMF, Matos MAR, Rio CMA,
Piedade CMGS. Thermochemical and theoretical study of some
methyldiazines. Struct Chem. 1996;7:329–36.
33. Stull RD, Westrum EF, Sinke GC. The chemical thermodynamics
of organic compounds. New York: Wiley; 1969.
34. Sabbah R, Xu-wu A, Chickos JS, Leita˜o MLP, Roux MV, Torres
LA. Reference materials for calorimetry and differential thermal
analysis. Thermochim Acta. 1999;331:93–204.
47. Tjebbes J. The heats of combustion and formation of the three
diazines and their resonance energies. Acta Chem Scand 1962;16:
916–21.
35. Monte MJS, Santos LMNBF, Fulem M, Fonseca JMS, Sousa
CAD. New static apparatus and vapor pressure of reference
materials: naphthalene, benzoic acid, benzophenone, and ferro-
cene. J Chem Eng Data. 2006;51:757–66.
48. Acree WE Jr, Powell JR, Tucker SA, Ribeiro da Silva MDMC,
Matos MAR, Gonc¸alves JM, et al. Thermochemical and theo-
retical study of some quinoxaline 1,4-dioxides and of pyrazine
1,4-dioxide. J Org Chem. 1997;62:3722–6.
36. Wagman DD, Evans WH, Parker VB, RH Shum, F Halow, SM
Bailey, KL Churney, RL Nuttall. NBS tables of chemical ther-
modynamic properties. J Phys Chem Ref Data 1982;11(Suppl 2).
123