Synthesis, structure, and properties of pyrazole-4-carbaldehyde oximes

Article abstract of DOI:10.1134/S1070363212100131

1-Alkyl-1H-pyrazole-4-carbaldehyde oximes reacted with acetic anhydride to give the corresponding nitriles, which is typical for anti isomers of aldoximes. The anti configuration of 5-methyl-1-propyl-1H-pyrazole-4-carbaldehyde oxime in crystal was unambig

Full text of DOI:10.1134/S1070363212100131

ISSN 1070-3632, Russian Journal of General Chemistry, 2012, Vol. 82, No. 10, pp. 1720–1723. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © O.S. Attaryan, A.A. Sahakyan, R.A. Tamazyan, A.G. Ayvazyan, G.V. Asratyan, 2012, published in Zhurnal Obshchei Khimii, 2012,
Vol. 82, No. 10, pp. 1716–1719.
Synthesis, Structure, and Properties
of Pyrazole-4-carbaldehyde Oximes
O. S. Attaryana, A. A. Sahakyana, R. A. Tamazyanb, A. G. Ayvazyanb, and G. V. Asratyana
a Institute of Organic Chemistry of Scientific Technological Center of Organic and Pharmaceutical Chemistry
and National Academy of Sciences of Armenia, Azatutyan av. 26, Yerevan, 0014 Armenia
e-mail: sahakyan.arsen@gmail.com
b Molecule Structure Research Center of Scientific Technological Center of Organic and Pharmaceutical Chemistry
and National Academy of Sciences of Armenia, Yerevan, Armenia
Received July 28, 2011
Abstract—1-Alkyl-1H-pyrazole-4-carbaldehyde oximes reacted with acetic anhydride to give the
corresponding nitriles, which is typical for anti isomers of aldoximes. The anti configuration of 5-methyl-1-
propyl-1H-pyrazole-4-carbaldehyde oxime in crystal was unambiguously determined by X-ray analysis.
DOI: 10.1134/S1070363212100131
Heterocyclic oximes are widely used as inter-
mediates in organic synthesis [1]. However, oximes of
the pyrazole range remain relatively poorly studied.
The goal of the present research was synthesis of 1-
alkyl-1H-pyrazole-4-carbaldehyde oximes and study
of their structure and chemical transformations.
As was expected [2–4], 1-alkyl-1H-pyrazole-4-
carbaldehydes I–IV were easily converted into the corres-
ponding oximes V–VIII by treatment with hydroxyl-
amine (Table 1). In the 1H NMR spectra (Table 2) of all
oximes V–VIII only spiting signal of OH group proton
was absent, indicating formation of only one isomer [5].
R2
C
N
R1
N
O
N
R2
CH
R1
R2
HON
R3
H
NH2OH
Ac2O
N
N
IХ_ХII
O
R1
N
N
R2
C
N
H
O
C
R3
R3
CH3
I_IV
V_VIII
R1
N
N
R3
I, V, IX, R1 = R2 = H, R3 = Me (a), Pr (c); II, VI, X, R1 = H, R2 = Me, R3 = Et (b), Pr (c); III, VII, XI: R1 = Me, R2 =
H, R3 = Et (b), Pr (c), IV, VIII, XII, R1 = R2 = Me, R3 = Me (a), Et (b), Pr (c).
NMR spectroscopy is one of the most reliable
methods for structure determination of isomeric oximes
[6–14]. According to [8], the difference between
chemical shifts of protons in the aldoxime group
(δOH – δCH) is specific for syn and anti isomers.
This difference is equal to ~3.0 ppm for syn isomers
of V–VIII, the difference δOH – δCH was from
2.3 to 2.8 ppm, which is typical of syn oximes.
Compounds V–VIII were thermally stable, and
1
according to H NMR spectra they neither changed
on heating in DMSO to 150°C nor underwent
syn–anti isomerization on heating in the presence
of HCl.
1
and ~4.0 ppm for anti isomer. In the H NMR spectra
1720

1721
SYNTHESIS, STRUCTURE, AND PROPERTIES OF PYRAZOLE-4-CARBALDEHYDE OXIMES
Table 1. Yields, physical constants, and elemental analyses of substituted pyrazoles V–XII
Found, %
Calculated, %
Comp.
no.
Yield, mp, °C or bp, °C
nD20
Formula
%
(mm)
C
H
N
C
H
N
89
80
89
91
90
97
113–114
85–87
–
–
–
–
–
–
48.24
54.73
54.73
57.48
54.73
57.48
5.72
7.00
7.00
7.78
7.00
7.78
33.29
27.65
27.65
25.14
27.65
25.14
C5H7N3O
C7H11N3O
C7H11N3O
C8H15N3O
C7H11N3O
C8H15N3O
48.00
54.90
54.85
57.32
54.63
57.54
5.60
7.18
7.22
7.69
7.20
7.39
33.60
27.45
27.51
25.00
27.52
25.38
Vа
Vc
103–105
85–87
VIb
VIc
VIIb
VIIc
105–107
109–111
91
87
88
85
88
85
90
88
80
75
80
78
183–185
173–175
125–127
95(1)
–
54.99
57.48
59.66
56.07
62.22
62.22
64.42
62.22
64.42
62.22
64.42
66.66
7.18
7.78
8.28
4.67
6.66
6.66
7.38
6.66
7.38
6.66
7.38
7.40
27.45
25.14
23.20
39.25
31.11
31.11
28.18
31.11
28.11
31.11
28.11
25.92
C7H11N3O
C8H13N3O
C9H15N3O
C5H5N3
54.65
57.23
59.78
56.25
62.48
62.48
64.71
62.31
64.25
62.38
64.02
66.38
7.00
7.39
8.44
4.81
6.86
6.36
7.09
6.82
7.42
6.93
7.21
7.63
27.68
25.38
23.48
39.93
31.32
31.39
28.34
30.99
28.36
31.29
27.95
25.40
VIIIа
VIIIb
VIIIc
IXа
–
–
1.4932
1.4964
1.4960
–
104(2)
102(1)
38–40
C7H9N3
IXc
C7H9N3
Xb
C8H11N3
C7H9N3
Xc
XIb
XIc
XIIа
XIIb
XIIc
105(1)
44–46
118(2)
112(1)
120(1)
1.4975
–
1.4996
1.4960
1.5076
C8H11N3
C7H9N3
C8H11N3
C9H12N3
It is also known [15] that syn-aldoximes react with
acetic anhydride forming acetyl derivatives and that
anti isomers under similar conditions are converted
into nitriles via elimination of water. We found that
treatment of oximes with acetic anhydride gave
exclusively pyrazole-4-carbonitriles IX–XII, i.e.
compounds V–VIII behaved like anti-aldoximes.
and were refined from diffraction angles of 22 reflec-
tions in the range 12 < θ < 14°; triclinic crystal system,
space group P-1; a = 7.607(3), b = 8.971(2), c =
9.161(3) Å; α = 117.15(3), β = 108.35(3), γ =
96.16(3)°; V = 504.2(5) Å3; Z = 2. Total of 3349 reflec-
tion intensities were measured in the range 0 ≤ h ≤ 10,
–12 ≤ k ≤ 12, –12 ≤ l ≤ 12, θmax = 30° (MoKα
irradiation, graphite monochromator). All calculations
were performed using SHELXTL software package
[16]. After averaging symmetrically equivalent reflec-
tions array contains 2927 non-equivalent reflections
(Rint = 0.012) of which 1891 observed with I > 2σ(I).
We believe that assignment of oximes V–VIII to
the syn or anti isomers on the basis of 1H NMR data is
not absolutely reliable. Therefore, the structure of 5-
methyl-1-propyl-1H-pyrazole-4-carbaldehyde oxime
(VIIc) was determined by X-ray analysis. According to
the X-ray diffraction data, the oxime group in VIIc has
anti configuration (see figure).
EXPERIMENTAL
1
The H NMR spectra were recorded on a Varian
Mercury spectrometer at 300 MHz from solutions in
DMSO-d6–CCl4 (1 : 3). The IR spectra were measured
on a Specord 75-IR instrument from thin films.
X-Ray analysis of compound VIIc. The unit cell
parameters were determined on an Enraf–Nonius
CAD-4 automatic diffractometer at room temperature
Structure of the molecule of 5-methyl-1-propyl-1H-pyrazole-
4-carbaldehyde oxime (VIIc) according to the X-ray
diffraction data.
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ATTARYAN et al.
Table 2. Parameters of IR and 1H NMR spectra of substituted pyrazoles V–XII
IR spectrum, ν, cm–1
Comp. no.
1H NMR spectrum (DMSO-d6), δ, ppm (J, Hz)
C=N or
C=N
ring
1510
1620
2.90 s (3H, NCH3), 7.19 s (1H, 5-H), 7.61 s (1H, 3-H), 8.18 s (1H, N=CH), 10.99 s (1H, OH)
0.91 t (3H, CH2CH3, J = 7.0), 1.95 q (2H, CH2CH3, J = 7.0, 7.4), 4.12 t (2H, NCH2, J = 7.4), 7.18 s
(1H, 5-H), 7.61 s (1H, 3-H), 8.18 s (1H, N=CH), 10.98 s (1H, OH)
1.39 t (3H, CH2CH3, J = 7.2), 2.21 s (3H, CH3), 4.0 q (2H, CH2CH3, J = 7.2), 7.10 s (1H, 5-H), 8.20 s
(1H, N=CH), 10.92 s (1H, OH)
0.91 t (3H, CH2CH3, J = 7.9), 1.85 q (2H, NCH2, J = 7.4), 7.10 s (1H, 5-H), 8.08 s (1H, N=CH), 10.78
s (1H, OH)
1.40 t (3H, CH2CH3, J = 7.2), 2.38 s (3H, 5-CH3), 4.12 q (2H, CH2CH3, J = 7.2), 7.11 s (1H, 3-HAr),
8.12 s (1H, N=CH), 10.72 s (1H, OH)
0.90 t (3H, CH2CH3, J = 7.9), 1.80 q (2H, CH2CH3, J = 7.4, 7.9), 2.37 s (3H, 5-CH3), 4.12 q (2H,
NCH2, J = 7.4), 7.11 s (1H, 3-HAr), 8.01 s (1H, N=CH), 10.78 s (1H, OH)
Va
Vc
1510
1510
1510
1520
1520
1640
1630
1640
1630
1630
VIb
VIc
VIIb
VIIc
1550
1550
1640
1610
2.10 s (3H, 3-CH3), 2.35 s (3H, 5-CH3), 3.61 s (2H, NCH3), 7.89 s (1H, N=CH), 10.21 s (1H, OH)
1.38 t (3H, CH2CH3, J = 7.2), 2.2 s (3H, 3-CH3), 2.32 s (5H, 5-CH3), 4.0 q (2H, CH2CH3, J = 7.2),
7.90 s (1H, N=CH), 10.29 s (1H, OH)
VIIIa
VIIIb
1530
1670
0.90 t (3H, CH2CH3, J = 7.9), 1.80 q (2H, CH2CH3, J = 7.4, 7.9), 2.1 s (3H, 3-CH3), 2.35 s (3H, 5-
CH3), 7.90 s (1H, N=CH), 10.21 s (1H, OH)
VIIIc
1520
1530
1520
2210
2230
2200
2.90 s (3H, NCH3), 7.18 s (1H, 5-H), 7.60 s (1H, 3-H)
1.41 t (3H, CH2CH3, J = 7.2), 2.30 s (3H, 3-HAr), 4.10 q (2H, NCH2, J = 7.2), 8.20 s (1H, 5-H)
0.91 t (3H, CH2CH3, J = 7.0), 1.95 q (2H, CH2CH3, J = 7.0, 7.4), 4.12 t (2H, NCH2, J = 7.4), 7.18 s
(1H, 5-H), 7.73 s (1H, 3-H)
IXa
Xb
IXc
1530
1530
1530
2230
2230
2230
1.40 t (3H, CH2CH3, J = 7.2), 2.42 s (3H, 5-CH3), 4.10 q (2H, CH2CH3, J = 7.2), 7.61 s (3H, 3-H)
0.92 t (3H, CH2CH3, J = 7.9), 1.85 q (2H, CH2CH3, J = 7.4, 7.9), 2.31 s (3H, 3-CH3), 8.20 s (1H, 5-H)
0.95 t (3H, CH2CH3, J = 7.9), 1.87 q (2H, CH2CH3, J = 7.4, 7.9), 2.41 s (3H, 5-CH3), 4.22 q (2H,
NCH2, J = 7.4), 8.45 s (1H, 3-H)
XIb
Xc
XIc
1550
1540
2240
2230
2.10 s (3H, 3-CH3), 2.38 s (3H, 5-CH3), 2.61 s (3H, NCH3)
0.95 t (3H, CH2CH3, J = 7.9), 4.95 q (2H, CH2CH3, J = 7.4, 7.9), 2.10 s (3H, 3-CH3), 2.37 s (3H, 5-
CH3), 4.0 t (2H, NCH2, J = 7.4)
XIIa
XIIb
1530
2230
1.41 t (3H, CH2CH3, J = 7.2), 2.10 s (3H, 3-CH3), 2.40 s (3H, 5-CH3), 4.20 q (2H, CH2CH3, J = 7.2)
XIIc
The structure was solved by the direct method, and the
coordinates of hydrogen atoms were determined from
the Fourier difference series. The structure was refined
by the full-matrix least-squares procedure in aniso-
tropic approximation for non-hydrogen atom and in
isotropic approximation for hydrogen atoms; final dis-
crepancy factor R = 0.057, goodness of fit S = 1.037.
were filtered off and recrystallized from water
containing a few drops of ethanol. The yields, physical
constants, elemental analyses, and spectral parameters
of compounds V–VIII are given in Tables 1 and 2.
General procedure for the synthesis of 1-alkyl-
1H-pyrazole-4-carbonitriles IX–XII. A mixture of
0.05 mol of oxime V–VIII and 100 ml of acetic anhyd-
ride was heated for 1 h under reflux. Excess acetic anhyd-
ride was removed, the residue was neutralized with
potassium carbonate and extracted with chloroform
(3 × 50 ml), the extract was dried over magnesium
sulfate, the solvent was distilled off, and the residue
was distilled under reduced pressure. The yields, physical
constants, elemental analyses, and spectral parameters
of compounds IX–XII are given in Tables 1 and 2.
General procedure for the synthesis of 1-alkyl-
1H-pyrazole-4-carbaldehyde oximes V–VIII.
A
solution of 0.1 mol of potassium hydroxide in 25 ml of
ethanol was added under stirring to a solution of 0.1
mol of hydroxylamine hydrochloride in 10 ml of water.
The precipitate of potassium chloride was filtered off,
a solution of 0.05 mol of aldehyde I–IV in 25 ml of
ethanol was added to the filtrate, and the white crystals
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SYNTHESIS, STRUCTURE, AND PROPERTIES OF PYRAZOLE-4-CARBALDEHYDE OXIMES
9. Guette, J.P., Armand, J., and Lacombe, L., C.R. Acad.
Sci., Ser. C, 1967, vol. 264, no. 17, p. 1509.
10. Burakevich, J.V., Lore, A.M., and Volp, G.P., J. Org.
Chem., 1971, vol. 36, no. 1, p. 1.
REFERENCES
1. Abele, E., Abele, R., and Lukevits, E., Khim.
Geterotsikl. Soedin., 2004, no. 1, p. 3.
11. Afonin, A.F., Ushakov, I.A., Tarasova, O.A., Shmidt, E.Yu.,
Mikhaleva, A.I., and Voronov, V.K., Russ. J. Org.
Chem., 2000, vol. 36, no. 12, p. 1837.
12. Moiseev, I.K., Kalinina, M.I., Strelenko, Yu.A., and
Khmel’nitskii, L.I., Zh. Obshch. Khim., 1988, vol. 58,
no. 1, p. 203.
13. Hawkes, E., Herwing, K., and Roberts, D., J. Org.
Chem., 1974, vol. 39, no. 8, p. 1017.
14. Del’ Pina, M., Budilin, V.A., Radriges, M., and Bun-
del’, Yu.G., Khim. Geterotsikl. Soedin., 1989, no. 2, p. 185.
15. Osnovy stereokhimii (Principles of Stereochemistry),
Terent’ev, A.P. and Potapov, M.V., Eds., Moscow:
Khimiya, 1964, p. 182.
2. Ocskay, G. and Vazgha, L., Tetrahedron, 1958, vol. 2,
nos. 1–2, p. 140.
3. Shapranova, N.I., Somin, I.N., and Kuznetsov, S.G.,
Khim. Geterotsikl. Soedin., 1973, no. 8, p. 1093.
4. Martirosyan, S.S., Khim. Zh. Arm., 2004, vol. 57, no. 3,
p. 90.
5. Attaryan, O.S., Antanosyan, S.K., Kinoyan, F.S.,
Tamazyan, R.A., Panosyan, G.A., and Matsoyan, S.G.,
Russ. J. Org. Chem., 2006, vol. 42, no. 12, p. 1868.
6. Karabatsos, G.J. and Taller, R.A., Tetrahedron, 1968,
vol. 24, no. 8, p. 3347.
7. Crepaux, D. and Lehn, J.M., Mol. Phys., 1968, vol. 14,
no. 2, p. 547.
16. Sheldrick, G.M., SHELXS97 and SHELXL97. Program
for the Refinement of Crystal Structure, Göttingen
(Germany): University of Göttingen, 1997.
8. Kleinspehn, G.G., Jung, J.A., and Studniarz, S.A.,
J. Org. Chem., 1967, vol. 32, no. 2, p. 460.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 10 2012