Structure and stability of isoxazoline compounds

Article abstract of DOI:10.1134/S107036321304018X

Structure of isoxazoline compounds formed via the reaction of alkyl-substituted benzonitrile oxides with ethylene was determined by X-ray diffraction method. Isoxazoline ring is flattened, the bond lengths in it depend slightly on the nature of substituents (CH₃, C₂H ₅) and their position in the benzene ring and the angle of rotation relative to the isoxazoline ring. The connection N-O has a length 1.422 A. Thermal decomposition of isoxazolines in a liquid phase (160-280 C) is accompanied by the release of acetaldehyde and aromatic nitrile. Both the structure of the cycle and its stability is practically independent of the structure of an aromatic substituent. The rate constant of the initial stage is characterized by the low significance of kinetic parameters, E = 104 8 kJ mol^-1 and log a(A/c) = 7.2±0.8. The results obtained are rationalized in terms of biradical mechanism of isoxazoline ring-opening that includes an efficient recombination of the biradical and its disappearance as a result of synchronous multi-center rearrangement with the release of acetaldehyde.

Full text of DOI:10.1134/S107036321304018X

ISSN 1070-3632, Russian Journal of General Chemistry, 2013, Vol. 83, No. 4, pp. 717–721. © Pleiades Publishing, Ltd., 2013.
Original Russian Text © T.K. Goncharov, V.V. Dubikhin, E.L. Ignat’eva, G.M. Nazin, Z.G. Aliev, S.M. Aldoshin, 2013, published in Zhurnal Obshchei
Khimii, 2013, Vol. 83, No. 4, pp. 634–639.
Structure and Stability of Isoxazoline Compounds
T. K. Goncharov, V. V. Dubikhin, E. L. Ignat’eva,
G. M. Nazin, Z. G. Aliev, and S. M. Aldoshin
Institute of Problems of Chemical Physics, Russian Academy of Sciences,
Chernogolovka, Moscow oblast, 142432 Russia
e-mail: tel@icp.ac.ru
Received March 23, 2012
Abstract—Structure of isoxazoline compounds formed via the reaction of alkyl-substituted benzonitrile oxides
with ethylene was determined by X-ray diffraction method. Isoxazoline ring is flattened, the bond lengths in it
depend slightly on the nature of substituents (CH3, C2H5) and their position in the benzene ring and the angle of
rotation relative to the isoxazoline ring. The connection N–O has a length 1.422 Å. Thermal decomposition of
isoxazolines in a liquid phase (160–280°C) is accompanied by the release of acetaldehyde and aromatic nitrile.
Both the structure of the cycle and its stability is practically independent of the structure of an aromatic
substituent. The rate constant of the initial stage is characterized by the low significance of kinetic parameters,
E = 104±8 kJ mol–1 and log a(A/c) = 7.2±0.8. The results obtained are rationalized in terms of biradical
mechanism of isoxazoline ring-opening that includes an efficient recombination of the biradical and its
disappearance as a result of synchronous multi-center rearrangement with the release of acetaldehyde.
DOI: 10.1134/S107036321304018X
A process of flow-temperature solidifying of
rubber based on the addition reaction of aromatic
dinitrile oxides on the double C=C bond has been
suggested in 1968 [1].
Et
CH
CH
Et
CH
Et
CH
Et
O
O
ONC
Et
CNO
Et
H
H
C
C
N
N
After synthesis of thermally stable and suitable for
technical applications sterically screened dinitrile
oxides of 2,4,6-triethylbenzene-1,5-dinitrile oxide type
[2] the method was developed and, in particular, was
used to of the polymer binders of solid rocket fuels [3–
5]. The formation of isoxazoline ring as a cross-linking
fragment of the binder means an appearance of new
structural component in the rocket fuel which may
affect the degradation of the cross-linked polymer and
the stability of the composition as a whole. Therefore,
the problem of thermal stability of isoxazolines
deserves detailed study. There is no information in the
literature on the kinetics of decomposition of pure
isoxazolines or their solutions in neutral media. In this
regard, we undertook a detailed kinetic study of the
decomposition of a simple isoxazoline ring formed as a
result of addition of a nitrile oxide group to ethylene in
two bifunctional compounds I and II simulating the
structure of cross-linked rubbers, and of two mono-
functional isoxazolines III and IV differing in the
degree of steric shielding of the five-membered ring
with alkyl groups of the substituted aromatic moieties.
Structure of isoxazolines. The structures of
compounds III and IV were determined by XRD
analysis. The information on the structure of I is given
in [6]. The general view of the molecules and the bond
lengths of the isoxazoline rings are given in the figure.
717

718
GONCHAROV et al.
R
O
O
O
O
N
N
N
N
R
R
I, II
III
IV
I, R = C2H5; II, R = CH3.
In the molecules of compound I and III the planes of
benzene and isoxazoline rings are almost orthogonal.
The dihedral angle between the planes is 84.6° and
85.4°, respectively. Isoxazoline ring has an envelope
conformation and is strongly flattened. Thus, in the
molecule of III the atom C is deviated from the plane
of other four atoms by 0.34 Å, and the bend on the line
О···С2 is 22.2°.
Alkyl substituents in the benzene cycle limit the
rotational movement of the isoxazoline cycle. When
there are two ortho-substituents in the benzene cycle,
the orthogonal arrangement of the rings is achieved. At
the same time, the substituents in the aromatic group
have a little effect on the structure and the bond
lengths of the isoxazoline ring. Regardless of the angle
of rotation of the five-membered ring relative to
benzene ring the bond lengths in the isoxazoline ring
of different molecules are the same within the defini-
tions error (see figure). The C3–C4 bond between the
rings is shortened and also slightly dependent on the
relative orientation of their planes. Probably, at the
perpendicular location of the rings the violation of
conjugation between the π-systems the benzene ring
and the C=N bond is compensated by the interaction of
n(N)σ type of an unshared electron pair of the nitrogen
atom lying in the plane of the five-membered ring with
A single crystal of connection of compound IV is
built of two crystallographically independent mole-
cules A and B. The isoxazoline ring in them is mate-
rially flat. The atom C1 is out of plane of the other ring
atoms by 0.11 and 0.03 Å for A and B, respectively,
and the bend at the line О···С2 is 7.4° and 1.8°,
respectively. The torsion angle N1C3C4C9 characteriz-
ing the rotation of the isoxazoline ring relative to
benzene moiety is equal to 4.3° (B) and 17.9° (A).
I
III
IVA
IVB
General view of molecules of compounds I, III, IVА, IVB in the crystal.
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STRUCTURE AND STABILITY OF ISOXAZOLINE COMPOUNDS
Table 1. Kinetic characteristics of decomposition of compounds I–IV in the liquid phase and in o-dichlorobenzene
Е,
K, s–1
Comp. no.
Medium
Temperature range, °С
log (A/c–1)
kJ mol–1
at 200°С
2.3×10–5
3.6×10–6
3.3×10–6
1.8×10–6
3.3×10–6
1.9×10–6
3.6×10–6
3.2×10–6
Liquid phase
Solution
160–220
190–250
190–220
230–250
170–220
230–270
180–230
230–270
106.3
109.7
112.6
123.5
112.6
112.6
113.0
113.4
7.1
I
6.66
6.95
7.90
6.95
6.69
7.03
7.02
Liquid phase
Solution
II
Liquid phase
Solution
III
IV
Liquid phase
Solution
the vacant π*-orbital of benzene ring, whose
symmetries coincide. It can be noted also that the N–O
bond is weakened, as well as all the bonds of >C=N–O,
and has a length of ~1.422 Å.
melt. This means that the reaction medium contributes
to the decomposition of the substance and the above-
mentioned solvents are inert compounds relative to I.
A similar effect of the m/V value on the decomposition
nature was observed for other isoxazolines, but unlike
compound I in the case of II–IV there is no significant
reduction in the reaction rate when dissolving in inert
solvents. These compounds react in the melt and in a
solution with virtually the same rate.
The packaging of molecules in the crystals of I, III,
IV is loose. In all the compounds there are no intermo-
lecular hydrogen bonds and shortened intermolecular
contacts. This means that factors like the association of
molecules and intramolecular spatial interactions of the
atoms cannot influence the reactivity of isoxazolines
and, in particular, the rate of their decomposition.
The parameters of the Arrhenius equation for the
rate constants of the non-catalytic decomposition step
in the liquid phase and in one of the inert solvent (o-
dichlorobenzene) at a concentration of 1 wt % by
weight and a comparison of the rate constants at 200°C
are shown in Table 1. It can be seen that all
compounds in the melt and in solution decompose with
almost equal rates. The maximal difference is less than
2 times. Only compound I in the melt has a higher
decom-position rate. In all cases, almost the same
activation energy was observed: Е 104±8 kJ mol–1 and
log (А/c) = 7.2±0.8. Such a low value of the pre-
exponential factor cannot match any elementary
reaction and demonstrates the complex mechanism that
includes reversible and consecutive stages. The data on
the composition of products, kinetic parameters, the
catalytic action of acetaldehyde and the influence of
the reaction medium can be and explainned in terms
of the biradical mechanism of decomposition of the
five-membered cyclic compounds [7], which corres-
ponds to the scheme bellow.
The kinetics of decomposition. The analysis of the
volatile and condensed products showed that the
decomposition of the isoxazoline ring in compounds I–
IV results in the corresponding aromatic nitrile and
acetaldehyde V, whose going out in the gaseous phase
was manometrically measured. Thus it was established
for compound I in the temperature range of 160–220°C
and at the degree of filling of vessel with the com-
pound (m/V, g cm–3) of ~0.002 the reaction obeys the
first order equation. Yield of compound V is 95 mol %.
When the m/V value increases 10 times, the
decomposition becomes autocatalytic, the yield of
acetaldehyde is reduced to 65%, the initial rate remains
unchanged. When the m/V values are high, the 1st
order rate constants calculated by the initial rate of
release of acetaldehyde on the assumption that in the
early stages its yield is 1 mol per one isoxazoline ring
coincided with the data obtained at low values m/V.
The acceleration degree increases with decreasing
temperature and increasing m/V. We conclude that
acetaldehyde accelerates the decomposition of the
isoxazoline ring. When dissolving compound I in
chlorobenzene, o-dichlorobenzene or naphthalene, the
first order reaction occurs. The rate of decomposition
in these solvents is reduced 5 times compared with the
The first step is the cleavage of the N–O bond,
which is the weakst in the ring. The biradical VI
formed recombines with recovery of the starting
compound, or is destroyed by the synchronous
rearrangement with the release of acetaldehyde and the
formation of aromatic nitrile. In addition, the
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720
GONCHAROV et al.
Ar
ArCN + CH3CHO
k2
k1
Ar
k3
N
k−1
+RH
N
O
ArC(N)CH2CH2O
ArC(NH)CH2CH2O
O
+ R
VI
The scheme of the stages of isoxazoline conversation.
bimolecular decomposition of the biradical VI is
possible as a result of the break off its by the radical
centers of the hydrogen atoms from the medium
molecules RH. In the inert solvents reaction (3) does
not occur. The observed rate constants kobs and the
kinetic parameters Еobs and Аobs are connected with the
parameters of the individual stages approximately as
follows:
recombination. Low pre-exponential factor is the result
of a high rate of recombination of the biradical VI and
low values А2 of
a
multi-center synchronous
decomposition of the biradical, which includes 1,2-
migration of the hydrogen through the triangular
transition state.
Acceleration of decomposition under action of
acetaldehyde and the decomposition rate of compound
I in the liquid phase, which is increased as compared
with the compounds II–IV, are due to the proceeding
of reaction (3), whose rate depends on the reactivity
(primarily the strength) of the С–Н bond in the
molecules RH and on their concentrations. In the
methyl groups of compound I, where the reaction (3) is
unnoticeable yet, the bond dissociation energy D(C–H)
can be estimated at 290 kJ mol–1 (less than in
mesitylene due to the influence of the extended system
of the π-bonds). For the methylene groups in I the
value D(C–H) is lower by at least 20 kJ mol–1 than that
kobs = k1k2/k–1, Еobs = Е1 + Е2 – Е–1, Аobs = А1А2/А–1.
The activation energies of the secondary processes
are low. Therefore we can assume that Еobs ≈ Е1. The
constancy of Еobs in the series of compounds I–IV
corresponds to the same length of N–O bond in these
compounds. The retardation of internal rotation around
the С3–С4 (due to conjugation of the C=N bond with
the benzene ring) and the С2–С3 bonds (due to the
steric effect of the alkyl substituent in the ortho-
position of the benzene group) promotes biradical
Table 2. Crystallographic parameters for structures III, IV
Parameter
IV
III
М
Т, K
175.22
293(2)
175.22
293(2)
Radiation
Mo
Мо
Space group
а, Å
b, Å
P212121
7.322(1)
13.931(2)
18.807(3)
1918.4(5)
8
P212121
7.721(2)
9.869(2)
12.823(3)
c, Å
V, Å3
977.1(3)
Z
4
d, g cm–3
1.213
0.078
1.191
0.076
μ, mm–1
F(000)
752
0.7×0.6×0.6
1.82–25.00
376
0.8×0.6×0.5
2.60–25.98
Crystal size, mm
Range of data collection, deg
Index ranges
Reflections collected/independent
Rint
–1 ≤ h ≤ 8, –1 ≤ k ≤ 16, –22 ≤ l ≤ 1
–9 ≤ h ≤ 9, 0 ≤ k ≤ 12, 0 ≤ l ≤ 15
1312/1209
2603/2417
0.0269
0.0156
Completeness, %
Refined parameters
GOOF F2
99.8
236
1.038
100.0
118
1.084
R-Factors on I > 2σ(I)
R-Factors on all reflections
CCDC
R1 0.0512, wR2 0.1462
R1 0.0629, wR2 0.1566
828197
R1 0.0508, wR2 0.1334
R1 0.0572, wR2 0.1371
828198
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 83 No. 4 2013

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STRUCTURE AND STABILITY OF ISOXAZOLINE COMPOUNDS
for the methyl groups in compound II. Apparently,
such decrease in D(C–H) value is sufficient for
reaction (3) to be competitive with reaction (2). The
action of aldehyde may also be due to the low strength
of the С–Н in this compound. In addition, the С–Н
bond in aldehydes is highly polar, which increases its
reactivity.
The reactor was a glass ampule of 0.5–5.0 ml capacity,
equipped with a sickle membrane with an arrow and
was placed into a metal housing with a window to
observe the arrow deflection. The pressure was
measured by a compensation method. This technique
allows to perform experiments at high temperatures in
almost all solvents, as well as to measure the kinetics
of decomposition at high degrees of filling of the vial
with the material.
The presented mechanism allows the prediction the
change of the stability of the isoxazoline ring of the
cross-linked polymer. Due to an increase in the
medium viscosity the coefficients of rotational and
translational diffusion of the biradical VI will
decrease. As a result, an increase in the rate of
recombination and the decrease in the rate of
bimolecular capture of the biradical with medium
molecules will be observed. Finally, the isoxazoline
ring in the solidified polymer may be more stable than
in compound I. Furthermore, the decomposition of the
isoxazoline ring formed when attaching the nitrile
oxide group to the long-chain olefin will not afford the
reactive aldehyde as from I, but a ketone having
stronger C–H bonds, which will lead to a decrease in
the rate of reaction of the biradical VI with the
decomposition products.
A set of experimental X-ray diffraction reflections
was obtained on an automatic four circle diffracto-
meter KM-4 (KUMA DIFFRACTION) with χ-
geometry by ω/2θ scanning at monochromatic MoKα-
radiation. Table 2 shows the crystallographic param-
eters for the investigated crystals. The structures were
solved by the direct method using SIR92 program [8],
followed by a series of calculations of electron density
maps. The hydrogen atoms were set geometrically.
Complete anisotropic (non-hydrogen atoms) refinement
by the least-squares method was performed by
SHELXL-97 software [9]. Corrections for extinction
were not introduced.
Full information on the investigated structures was
deposited in the Cambridge Crystallographic Data Center.
From the standpoint of long-term storage, isoxa-
zoline compounds studied have a relatively high stab-
ility. Thus, the time of 1% degradation of compound I
in closed vessels at 60 and 40°C is 1 and 11 years,
respectively.
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EXPERIMENTAL
Isoxazolines were synthesized by bubbling ethylene
through 30% solution of the corresponding nitrile
oxide in chloroform at room temperature. The reaction
progress was monitored by IR spectroscopy by the
disappearance of the absorption bands of CNO group
at 1321 and 2294 cm–1. The reaction proceeds quanti-
tatively. Recrystallization from chloroform affords
compounds I (mp 75°C), II (mp 165–169°C), III (mp
73–74°C), and IV (mp 50–52°C).
The products were analyzed by GC-MS using a
Clarus-500 Perkin Elmer instrument [capillary column
(l 30 m, d 0.25 mm), the adsorbent Elite-5MS, carrier
gas helium, flow rate 1 ml min–1, the evaporator
temperature 120°C, column temperature 75°C].
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Kinetic measurements were carried out by means of
manometric device, designed for pressures up to 100 at.
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ture Analysis, University of Göttingen, Germany, 1998.
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