Alternative reaction medium for the synthesis of 1-propargylpyrazoles

Full text of DOI:10.1134/S1070363215070348

ISSN 1070-3632, Russian Journal of General Chemistry, 2015, Vol. 85, No. 7, pp. 1773–1774. © Pleiades Publishing, Ltd., 2015.
Original Russian Text © G.B. Zakaryan, S.S. Hayotsyan, H.S. Attaryan, G.V. Hasratyan, 2015, published in Zhurnal Obshchei Khimii, 2015, Vol. 85, No. 7,
pp. 1212–1213.
LETTERS
TO THE EDITOR
Alternative Reaction Medium for the Synthesis
of 1-Propargylpyrazoles
G. B. Zakaryan, S. S. Hayotsyan, H. S. Attaryan, and G. V. Hasratyan
Institute of Organic Chemistry, Scientific and Technological Center of Organic and Pharmaceutical Chemistry,
National Academy of Sciences of the Republic of Armenia, pr. Azatutyan 26, Yerevan, 0014 Armenia
e-mail: shayotsyan@gmail.com
Received May 7, 2015
Keywords: alternative reaction medium, 3-nitro-1,2,4-triazole, pyrazole, propargyl bromide, alkylation
DOI: 10.1134/S1070363215070348
Synthesis of N-propargyl substituted heterocycles
and development of available and technologically
simulated processes for their preparation are among the
goals of organic chemistry due to the fact that these
compounds are starting materials for producing
polyconjugated polymer compounds with semicon-
ductor properties and components used for the
synthesis of radio-pharmaceuticals [1].
However we failed to obtain 1-propargyl-3-nitro-1,2,4-
triazole II from 3-nitro-1,2,4-triazole under these
conditions. The use of an aqueous solution of N-
methyl-morpholine N-oxide (NMO) as the reaction
medium and potassium hydroxide as catalyst made it
possible to obtain 3-nitro-1-propargyl-1,2,4-triazole II
in 53% yield, therewith the formation of allene by-
product was not observed (Scheme 1).
The methods of obtaining of 1-propargylpyrazoles
under phase transfer catalysis [2, 3], as well as by
catalysis with potassium carbonate [4] are known.
Reacting pyrazole IIIa, 3(5)-methylpyrazole IIIb,
and 3,5-dimethylpyrazole IIIc with propargyl bromide
under similar conditions led to the formation of the
Scheme 1.
NO2
NO2
N
N
NMO, H2O
+ Br
N
N
53%
KOH, 20oC
N
N
H
II
I
Scheme 2.
R2
R2
NMO, H2O
KOH, 20oC
+
N
Br
N
R1
R1
N
N
H
IIIa−IIIc
66−79%
IVa−IVd
R1 = R2 = H (IIIa, IVa); R1 = CH3, R2 = H (IIIb, IVb); R1 = H, R2 = CH3 (IIIb, IVc); R1 = R2 = CH3 (IIIc, IVd).
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ZAKARYAN et al.
corresponding 1-propargylpyrazoles IVa–IVd in 66–
79% yields (Scheme 2).
spectrum (DMSO-d6), δ, ppm (J, Hz): 2.39 s (3H,
3-CH3), 2.21 br.s (3H, 5-CH3), 2.90 t (1H, ≡CH, J 2.6),
4.84 d (2H, NCH2, J 2.2), 5.97 d (1H, H4, J 2.2), 7.20 d
(1H, H3, J 2.2), 7.49 d (1H, H5, J 2.2).
Hence, the use of aqueous N-methylmorpholine N-
oxide and an equimolar amount of potassium hyd-
roxide can serve as an alternative medium to obtain 3-
nitro-1-propargyl-1,2,4-triazole and 1-propargylpyrazoles.
3,5-Dimethyl-1-propargylpyrazole (IVd) was
prepared similarly from 9.6 g (0.1 mol) of 3,5-di-
methylpyrazole IIIc and 21 mL (0.24 mol) of pro-
pargyl bromide. Yield 10.5 g (78%), bp 59°C (1 mmHg),
n2D0 1.4990. IR spectrum, ν, cm–1: 2100 (C≡CH), 1510
(ring). 1Н NMR spectrum (DMSO-d6), δ, ppm (J, Hz):
2.12 s (3H, 3-CH3), 2.29 d (3H, 5-CH3, J 0.8), 2.76 t
(1H, ≡CH, J 2.6), 4.75 d (2H, NCH2, J 2.6), 5.73 q
(1H, H4, J 0.8).
1H and 13C NMR spectra (DMSO-d6–CCl4, 1 : 3,
300 K) were obtained on a Varian Mercury-300VX
spectrometer operating at 300.05 and 75.46 MHz,
respectively, internal reference TMS. IR spectra (thin
layer) were recorded on a Specord 75 IR instrument.
3-Nitro-1-propargyl-1,2,4-triazole (II). A mixture
of 11.4 g (0.1 mol) of 3-nitro-1,2,4-triazole I, 9 g
(0.15 mol) of potassium hydroxide, and 50 mL of 50%
aqueous N-methylmorpholine-N-oxide solution was
stirred for 1 h at 80°C. Next, 15 mL (0.15 mol) of
propargyl bromide was added dropwise, and the
mixture was stirred at 20°C for 5 h. The reaction
product was extracted with chloroform. The extract
was washed with water and dried over magnesium
sulfate. After removing the solvent, the residue was
distilled in a vacuum. Yield 8 g (53%), bp 155°C
(1 mmHg). IR spectrum, ν, cm–1: 2100 (C≡CH), 1500
(ring). 1Н NMR spectrum (DMSO-d6), δ, ppm (J, Hz):
3.24 t (1H, ≡CH, J 2.6), 5.27 d (2H, NCH2, J 2.6), 8.79
s (1H, H5).
ACKNOWLEDGMENTS
This work was supported by the State Committee
on Science of the Ministry of Education and Science of
the Republic of Armenia (project SCS 13Ap-2e031).
1-Propargylpyrazole (IVa) was prepared similarly
from 3.4 g (0.05 mol) of pyrazole IIIa and 10 mL
(0.12 mol) of propargyl bromide. Yield 3.5 g (66%),
bp 80°C (1 mmHg), nD20 1.4960. IR spectrum, ν, cm–1:
2120 (C≡CH), 1500 (ring). 1Н NMR spectrum
(DMSO-d6), δ, ppm (J, Hz): 2.96 t (1H, ≡CH, J 2.6),
4.95 d (2H, NCH2, J 2.6), 6.21 d. d (1H, H4, J 2.4, 1.6),
7.36 d. d (1H, H3, J 1.6, 0.8), 7.65 d. d (1H, H5, J 2.4,
0.8).
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3(5)-Methyl-1-propargylpyrazole (IVb,c) was
prepared similarly from 8.2 g (0.1 mol) of 3(5)-methyl-
pyrazole IIIb and 21 mL (0.24 mol) of propargyl
bromide. Yield 9.5 g (79%), bp 45–48°C (1 mmHg),
n2D0 1.500. A ratio of isomer IVb : IVc = 2.5 : 1. IR
spectrum, ν, cm–1: 2100 (C≡CH), 1510 (ring). 1Н NMR
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 85 No. 7 2015