Reactions of trans-1-(β-aroylvinyl)pyridinium bromides with hydroxylamine hydrochloride

Article abstract of DOI:10.1134/S1070363215050138

Reactions of trans-1-(β-aroylvinyl)pyridinium bromides with hydroxylamine hydrochloride lead to a mixture of substituted isoxazoles regardless of the substituent nature in the aromatic core and the solvent.

Full text of DOI:10.1134/S1070363215050138

ISSN 1070-3632, Russian Journal of General Chemistry, 2015, Vol. 85, No. 5, pp. 1078–1081. © Pleiades Publishing, Ltd., 2015.
Original Russian Text © R.Dzh. Khachikyan, Z.G. Hovakimyan, G.A. Panosyan, R.A. Tamazyan, A.G. Ayvazyan, 2015, published in Zhurnal Obshchei
Khimii, 2015, Vol. 85, No. 5, pp. 781–784.
Reactions of trans-1-(β-Aroylvinyl)pyridinium Bromides
with Hydroxylamine Hydrochloride
R. Dzh. Khachikyan, Z. G. Hovakimyan, G. A. Panosyan,
R. A. Tamazyan, and A. G. Ayvazyan
Institute of Organic Chemistry, Scientific-Technological Center of Organic and Pharmaceutical Chemistry,
National Academy of Sciences of Armenia, ave. Azatutyan 26, Yerevan, 0014 Armenia
e-mail: khachikyanraya@gmail.com
Received November 20, 2014
Abstract—Reactions of trans-1-(β-aroylvinyl)pyridinium bromides with hydroxylamine hydrochloride lead to
a mixture of substituted isoxazoles regardless of the substituent nature in the aromatic core and the solvent.
Keywords: trans-1-(β-aroylvinyl)pyridinium bromide, hydroxylamine hydrochloride, oxazole, oxime, nucleophilic
addition
DOI: 10.1134/S1070363215050138
We have recently proposed a convenient method to
prepare trans-1-(β-aroylvinyl)pyridinium bromides
from trans-β-aroylacrylic acids [1]. In this work we
attempted to introduce the electron-withdrawing group
other than carboxyl into the molecule of β-aroylacrylic
acids and compared the behavior of the starting and
final compounds in the reaction with hydroxylamine
hydrochloride.
ring (donor methyl group reduces the electrophilicity
of the carbonyl group and directs the nucleophilic
attack to the C=C double bond) and on the solvent
nature [2] (Scheme 1).
However, interaction of trans-1-(β-aroylvinyl)pyri-
dinium bromides with hydroxylamine hydrochloride
under the same conditions led to unexpected results.
Regardless of the nature of the substituent in the
aromatic core, the reaction performed in methanol or
acetonitrile medium afforded a mixture of the
corresponding 3-aryl-1,2-oxazole Ia–Ic and 5-aryl-1,2-
oxazole IIa–IIc in the ratio of 1 : 1, 3 : 2, and 3 : 2,
respectively (Table 1).
It has been earlier found that the reaction of
hydroxylamine hydrochloride with trans-β-aroylacrilic
acids occurs via nucleophile attack at the carbonyl
group or C=C double bond. The reaction direction
depends on the nature of the substituent in the aromatic
Scheme 1.
O
+
COOH
NH2OH HCl
CH3CN
CH3OH
NH2
COOH +
NH2
COOCH3
O
O
NOH
COOH
1078

REACTIONS OF trans-1-(β-AROYLVINYL)PYRIDINIUM BROMIDES
1079
Scheme 2.
NOH
а
+
R
R
N
Br−
+
N
N
O
Br−
R
N
HBr
N
O
Iа−Ic
HO
O
+
N
+
Br−
NH
N
b
+
Br−
+
NH2OH HCl
R
N
R
NH
−H2O
O
Br−
O
R
N
O
HBr N
R
IIа−IIc
−H2O
O
O
c
R
R
O
NOH
R = СН3 (a), Сl (b), Br (c).
The reaction could occur via the three independent
pathways a–c (Scheme 2).
by dehydration and pyridine elimination to yield
compounds IIa–IIc. Formation of compounds IIa–IIc
(c) could occur via initial hydrolysis of the starting
vinylpyridinium salt to form the corresponding alde-
hyde, followed by isomerization and cyclization of its
oxime into the hemiketal and dehydration of the latter.
Formation of 3-aryl-1,2-oxazoles Ia–Ic (a) included
nucleophilic addition to the carbonyl group to form the
oxime, followed by intramolecular nucleophilic addition
at the double bond with elimination of pyridine.
The reaction pathway b included nucleophilic
addition at the double bond to give the enol under-
going further cyclization into the hemiketal followed
The structures of the compounds obtained were
confirmed by H NMR spectroscopy (Table 2) and X-
ray diffraction analysis (Table 3).
1
Table 1. Yield and elemental analysis data for 3(5)-aryl-1,2-oxazoles І and ІІ
Yield, %
Found, %
H
Calculated, %
H
Compound
Formula
I
II
C
N
C
N
75.43
65.30
48.27
5.68
3.58
2.63
8.76
8.44
6.23
C10H9NO
C9H6ClNO
C9H6BrNO
75.47
65.25
48.21
5.66
3.62
2.67
8.80
8.45
6.25
а
b
c
35.4
40.7
41.2
35.4
26
26.4
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 85 No. 5 2015

1080
KHACHIKYAN et al.
Table 2. 1H NMR spectral data for compounds Ia–Ic, IIa–IIc
Table 3. Crystal structure data for [3(5)-p-bromophenyl]oxazoles
Ic and IIc
Comp.
no.
δ (DMSO-d6–CCl4, 1 : 3), ppm
Parameter
Formula
Value
Iа + IIа 2.2.41 br. s (3H, CH3), 6.65 d (0.5H, =CH, J 1.9 Hz),
6.80 d (0.5H, =CH, J 1.7 Hz), 7.22–7.29 m (2H,
C6H4), 7.67–7.73 m (2H, C6H4), 8.31 d (0.5H,
=CHO, J 1.9 Hz), 8.66 d (0.5H, =CHO, J 1.7 Hz)
Ib + IIb 6.81 d (0.6H, =CH, J 1.9 Hz), 6.91 d (0.4H,
=CH, J 1.7 Hz), 7.43–7.50 m (2H, C6H4), 7.81–
7.88 m (2H, C6H4), 8.36 d (0.6H, =CHO, J 1.9 Hz),
8.72 d (0.4H, =CHO, J 1.7 Hz)
C9H6BrNO
224.05
М
Crystal system
Space group
Monoclinic
P21/c
a, Å
b, Å
c, Å
10.453(2)
13.985(3)
5.8387(12)
Ic + IIc 6.81 d (0.6H, =CH, J 1.9 Hz), 6.91 d (0.4H,
=CH, J 1.7 Hz), 7.58–7.65 m (2H, C6H4), 7.74–
7.81 m (2H, C6H4), 8.36 d (0.6H, =CHO, J 1.9 Hz),
8.71 d (0.4H, =CHO, J 1.7 Hz)
β, deg
V, Å3
Z
96.23(3)
848.5(3)
4
d
calc, g cm–3
1.754
μ(MoKα), mm–1
4.789
According to the XRD data, the ratio of isomers Ib
and IIb molecules in the crystal was of 60 : 40 (see
figure). Main crystallographic and structure refinement
data are listed in Table 3.
F(000)
440
Crystal size, mm
Т, K
0.25 × 0.32 × 0.40
293
λ, Å
0.71073
2.0, 30.0
In summary, reactions of trans-1-(β-aroylvinyl)-
pyridinium bromides with hydroxylamine hydro-
chloride yielded a mixture of 3(5)-aryl-1,2-oxazoles
regardless of the nature of the substituent in the
aromatic ring and the solvent nature.
θmin, θmax, deg
Scan ranges
–14 ≤ h ≤ 14; –19 ≤ k ≤ 0; 0 ≤ l
≤ 8
Reflections collected
2698
1186
Reflections observed
[I > 2.0 σ(I)]
R, wR2
0.0548, 0.1569
EXPERIMENTAL
1H NMR spectra were recorded with a Varian
Mercury-300 instrument at 303 K operating at
300.08 MHz relative to internal TMS reference.
Single-crystal X-ray diffraction analysis was carried
out at room temperature using an Enraf-Nonius CAD-4
automatic diffractometer [graphitic monochromator,
λ(МоKα) = 0.71073 Å, ω/2θ-scanning]. The unit cell
parameters were determined and refined accounting for
24 diffraction peaks (13.5 ≤ θ 15.0). The absorption
was accounted for using the experimental azimuthal
scanning curves (Tmin = 0.38205, Tmax = 0.71448) [3].
The structure was solved by direct method. Hydrogen
atoms were placed in the geometrically determined
positions and refined via a rider model [bond length
C–H 0.93 Å, Uiso(H) = 1.2Ueq(C)]. The structure was
refined by full-matrix anisotropic approximation for
non-hydrogen atoms, and the hydrogen atoms were
General view of the isomeric molecules Ib and IIb. Thermal
ellipsoids are shown with 50% probability.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 85 No. 5 2015

REACTIONS OF trans-1-(β-AROYLVINYL)PYRIDINIUM BROMIDES
1081
refined isotropically. The computations were per-
formed using SHELXTL software [4].
pitated with diethyl ether. The resulting precipitate was
filtered off, washed with ether, and dried in vacuum.
REFERENCES
Crystallographic CIF data were deposited at the
Cambridge Crystallographic Data Centre (CCDC 1027243).
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3. North, A.C.T., Phillips, D.C., and Mathews, F.S., Acta
Crystallogr. (A), 1968, vol. 24, p. 351. DOI: 10.1107/
S0567739468000707.
3(5)-Aryl-1,2-oxazoles (I, II). A solution of 0.62 g
(0.009 mol) of hydroxylamine hydrochloride in a
minimum amount of water was added to a saturated
solution of 0.0015 mol of trans-1-(β-aroylvinyl)pyri-
dinium bromide in acetonitrile or methanol. The
reaction mixture was refluxed during 27–30 h, cooled,
and poured into 200 mL of water. The reaction pro-
ducts were extracted with chloroform and re-preci-
4. Sheldrick, G.M., Acta Crystallogr. (A), 2008, vol. 64,
p. 112. DOI: 10.1107/S0108767307043930.
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