A convenient synthesis of novel 4-(1,2,4-triazol-1-yl)-2-pyrazolines and their derivatives

Article abstract of DOI:10.1081/SCC-120018754

Upon the study of powerful insecticidal and fungicidal properties of 1-phenylcarbamoyl-2-pyrazolines and 1,2,4-triazoles compounds, a variety of novel 4-(1,2,4-triazol-1-yl)-pyrazolines and their derivatives were prepared in good yields. The structures of these compounds were confirmed with ¹H NMR, MS, IR and elemental analyses.

Full text of DOI:10.1081/SCC-120018754

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A Convenient Synthesis of Novel 4-(1,2,4-Triazol-1-
yl)-2-pyrazolines and Their Derivatives
Shuowen Wang a , Bojie Shi a , Yuchang Li a , Qingmin Wang a & Runqiu Huang a
a Research Institute of Elemento-Organic Chemistry , State Key Laboratory of Elemento-
Organic Chemistry , Nankai University , Tianjin, P.R. China
Published online: 16 Aug 2006.
To cite this article: Shuowen Wang , Bojie Shi , Yuchang Li , Qingmin Wang & Runqiu Huang (2003) A Convenient Synthesis of
Novel 4-(1,2,4-Triazol-1-yl)-2-pyrazolines and Their Derivatives, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 33:9, 1449-1457, DOI: 10.1081/SCC-120018754
To link to this article: http://dx.doi.org/10.1081/SCC-120018754
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 9, pp. 1449–1457, 2003
A Convenient Synthesis of Novel 4-(1,2,4-
Triazol-1-yl)-2-pyrazolines and Their Derivatives
*
Shuowen Wang, Bojie Shi, Yuchang Li, Qingmin Wang,
and Runqiu Huang
Research Institute of Elemento-Organic Chemistry,
State Key Laboratory of Elemento-Organic Chemistry,
Nankai University, Tianjin, P.R. China
ABSTRACT
Upon the study of powerful insecticidal and fungicidal properties of
1-phenylcarbamoyl-2-pyrazolines and 1,2,4-triazoles compounds, a
variety of novel 4-(1,2,4-triazol-1-yl)-pyrazolines and their derivatives
were prepared in good yields. The structures of these compounds were
1
confirmed with H NMR, MS, IR and elemental analyses.
The laboratories of Philips–Duphar (Mulder et al.) discovered
3-(4-chlorophenyl)-1-(4-chlorophenylcarbamoyl)-2-pyrazoline (PH60-41)
*Correspondence: Shuowen Wang, Research Institute of Elemento-Organic
Chemistry, State Key Laboratory of Elemento-Organic Chemistry, Nankai
University, Tianjin 300071, P.R. China.
1449
DOI: 10.1081/SCC-120018754
Copyright & 2003 by Marcel Dekker, Inc.
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1450
Wang et al.
was a novel, highly active insecticide in 1975.[1] Subsequently in alarge
number of literatures[2–6] this kind compound was reported and found a
lot of good insecticides with broad spectrum, such as PH60-42,[7]
RH3421[8] (Fig. 1). Results of the relationship of the structure and activity
indicated the substitution in 3,4,5 positions of the pyrazline provided
variety for activities, hence subsequent researches focused on this point.
In 1997, Rainer et al. reviewed the development of 2-pyrazolines.[6]
They studied the relationship of the structure and the activity, and
introduced heterocycles into 4-position especially, bonded via nitrogen
to C-4 atom and prepared a series of azole-substituted pyrazoline. At the
same time, 1,2,4-triazole is an active group in fungicides. Therefore, in a
search for new insecticides and fungicides, in this article we bonded via
nitrogen atom 1,2,4-triazole to C-4 atom of 2-pyrazolines and t-butyl to
C-3 atom, and synthesized a variety of novel 4-(1,2,4-triazol-1-yl)-
pyrazolines and their derivatives.
When 3,3-dimethyl-1-(1,2,4-triazol-1-yl)-2-butanone (I1) was reacted
with aqueous formaldehyde in piperidine and methanol, many
by-products was formed and could not be separated easily.[9] We found
that 4,4-dimethyl-2-(1,2,4-triazol-1-yl)-1-penten-3-one (I1) was prepared
by addition of formaldehyde and elimination of water as shown in Sch. 1.
a,b- unsaturated ketones (I1–3) were treated with hydrazine hydrate
to yield pyrazolines (II1–3). We found that compound II-1 is not stable in
atmosphere, it must be stored in inert gases and in low temperature.
Further condensation with isocyanate or isothiocyanate provided a
variety of novel 4-(1,2,4-triazol-1-yl)-pyrazolines III1–22 in good yields
as shown in Sch. 2. The reaction activity of isothiocyanate was
much lower than isocyanate. When the compounds II were treated
with isocyanate, the reaction could smoothly provide precipitate
product, whereas the compounds II were treated with isothiocyanate,
several drops triethylamine must be added and the reaction need
above 10 h.
When 4-(1,2,4-triazol-1-yl)-pyrazoline III7 were reacted with methyl
iodide, compound IV was obtained in 70% yield as shown in Sch. 2.
Figure 1.

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4-(1,2,4-Triazol-1-yl)-2-pyrazolines
1451
Scheme 1.
Scheme 2.
All the products were white powders, and their structures were
confirmed by 1H NMR, MS, IR spectroscopy, and by elemental analysis.
The data were listed in Table 1.
The IR spectra(KBr) of III20 had a strong absorption at 1672 cmꢀ1
,
characteristic of a carbonyl group. 3379 cmꢀ1 (s) corresponds to N–H
stretching absorption, 3089 and 2954 cmꢀ1 were C–H stretching
absorption bands.
The 1H NMR data of all the products were listed in Table 2. We can
see from the data, proton of the t-butyl, which should be at the range of
1.0–1.2. The proton of 1,2,4-triazole, which should be at the range of
ꢀ 7.5–9.5 (two single peaks). But for the X, it aroused the difference
between the solubility in solvent. When X is O, we found that the title
compounds could be dissolved in CDCl3, whereas when X is S, the title

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1452
Wang et al.

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4-(1,2,4-Triazol-1-yl)-2-pyrazolines
1453

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1454
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4-(1,2,4-Triazol-1-yl)-2-pyrazolines
1455

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1456
Wang et al.
compounds could be dissolved only in DMSO. The peak of N–H could
1
be seen in the picture of H NMR when used CDCl3 as the solvent, but
not be seen when used DMSO as the solvent.
EXPERIMENTAL
General
1H NMR spectrawere recorded with aBruker AC-P200 spectro-
meter; reported chemical shifts were in ppm (ꢀ) relative to TMS (ꢀ
0.00). Infrared spectra were recorded on a Shimadzu corporation chart
200-91527 instrument, using KBr plate. Mass spectra were made with a
MS-7070 mass spectrometer using the EI method. Melting point were
determined by using a Thomas–Hoover apparatus and uncorrected.
Elemental analyses were carried out with Yanaco CHN Corder MT-3
elemental analyzer.
Synthesis of Intermediates
3,3-Dimethyl-1-(1,2,4-triazol-1-yl)-2-butanone,1-(2-chlorophenyl)-4,4-
dimethyl-2-(1,2,4-triazol-1-yl)-1-penten-3-one (I2) and 1-(2,4-dichloro-
phenyl)-4,4-dimethyl-2-(1,2,4-triazol-1-yl)-1-penten-3-one
bought.
(I3)
were
4,4-Dimethyl-2-(1,2,4-triazol-1-yl)-1-penten-3-one (I1): Mixed 90.0 g.
of 3,3-dimethyl-1-(1,2,4-triazol-1-yl)-2-butanone (0.5 mole) and 130 mL
of aqueous formaldehyde (37–40%), in 30 mL water, refluxed for 4 h.
After cooling the precipitate white solid formed. Collected the white
solid and dried. Mixed 42.8 g of above solid (0.2 mol) and 150 mL of
acetic anhydride, stirrered and heated to 106–109ꢁC for 3 h, moved the
acetic anhydride, distilled in reduced pressure. Collected
90–2ꢁC/0.2 mm Hg 31.2 g of distillation, yielding 36%.
Synthesis of the Product II–IV
3-t-Butyl-5-(2,4-dichlorophenyl)-4-(1,2,4-triazol-1-yl)-2-pyrazoline (II):
A mixture of 32.4 g (0.1 mol) of 1-(2,4-dichlorophenyl)-4,4-dimethyl-2-
(1,2,4-triazol-1-yl)-1-buten-3-one (I3) and 17.7 g (0.30 mol) of hydrazine
hydrate in 100 mL ethanol, was refluxed for 4 h, moved the solvent, after

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4-(1,2,4-Triazol-1-yl)-2-pyrazolines
1457
cooling, the precipitate white solid collected and washed with cold ether.
Yield 80.3%, m.p. 132–134ꢁC.
3-t-Butyl-5-(2,4-dichlorophenyl)-1-(3,4-dichlorophenylcarbamoyl)-
4-(1,2,4- triazol-1-yl)-2-pyrazoline (III): To stirred suspension of 6.8 g of
II (0.02 mol) in 50 mL of dry ether, 4.0 g of 3,4-dichlorophenyl isocya-
nate (0.02 mol) was added. The solution became clear and a precipitate
of the reaction mixture appeared. After stirring for 2 h, the precipitate
was collected and dried, recrystallized with acetonitrile, yielding 9.3 g
(88.5%), of compound III, m.p. 216–218ꢁC. IR: ꢁCO ¼ 1672 cmꢀ1
,
ꢁNH ¼ 3379 cmꢀ1, ꢁCH ¼ 3089 and 2954 cmꢀ1. MS: m/z 253 (100%).
3-t-Butyl-1-(N-phenyl-N-methyl)thiocarbamoyl-4-(1,2,4-triazol-1-yl)-2-
pyrazoline (IV): To asolution of 6.6 g of III (0.02 mol), in 50 mL of
dimethylformamide, 1.4 g of powered potassium hydroxide (0.025mol)
was added, and stirred for 15 min, then 2.8 g of methyl iodide (0.02 mol)
was added. After stirred for 0.5 h, the reaction mixture was poured into
ice water. The resulting precipitate was stirred for another 2 h, and
washed with methanol and petroleum ether, recrystallized with acetonitrile,
yielding 70%, m.p. 104–106ꢁC.
REFERENCES
1. Mulder, R.; Wellinga, K.; Van Daalen, J.J. Naturwissenschaften
1975, 62, 531–532.
2. Wellinga, K.; Grosscurt, A.C.; Van Hes, R. J. Agric. Food Chem.
1977, 25, 987–992.
3. Van Hes, R.; Wellinga, K.; Grosscurt, A.C. J. Agric. Food Chem.
1978, 26, 915–918.
4. Ozawa, K.; Nakayima, Y.; Tsugeno, M., et al. EP 058424, 1982.
5. Neh, H.; Buhmann, U.; Wegner, P., et al. EP 227055, 1987.
¨
6. Rainer, F.; Bernd, G.; Christoph, E., et al. Pestic. Sci. 1997, 50 (4),
333–337.
7. Grosscurt, A.C.; Van Hes; Wellinga, K. J. Agric. Food Chem. 1979,
27, 406–408.
8. Jacobson, R.M. US 4,663,341, 1987.
9. Chuchi Tang; Yuchang Li; Bing Chen, et al. Pestic. Chem. 1997, 432.
Received in Japan March 27, 2002

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