Mendeleev Commun., 2014, 24, 161–162
O
1
5
2''
HN
H
3''
N
NH
3
1'
7
4
2
–300
–250
–200
–150
6
N
4'
MeO
2'
3'
8b
(a)
(b)
145
147
149
151
153
155
141
142
143
144
145
146
147
148
149
10
8
6
4
F2/ppm
Figure 2 A fragment of the 2D 1H-15N HMBC spectrum (600 MHz, DMSO-d6)
of compound 8b.
157
4.20 4.10 4.00 3.90
11.4 11.3 11.2 11.1
d/ppm
d/ppm
(d 146.57) atoms [Figure 1(a)]. The interactions of the hydrogen
atoms at N2 (d 11.27) with C4 (d 146.57) and C1 (d 156.35) atoms
of the triazolone moiety [Figure 1(b)] are also characteristic.
The 1H-15N HMBC spectrum contains cross-peaks between the
doublet of protons at C6 (d 3.96, J 5 Hz) and the N5 (d –236.72),
N3 (–119.52) atoms. A correlation of the protons at C2', C2'' of the
aromatic moiety (d 6.58, J 8 Hz) with the N7 atom (d –323.51)
is also observed. Furthermore, interactions of the hydrogen
atom at N2 (d 11.27) with the N5 (d –236.72), N2 (–213.15), and
N3 (–119.52) atoms of the triazolone moiety are characteristic
(Figure 2).
In conclusion, we have developed a new convenient approach
to the synthesis of hitherto unknown substituted 5-arylamino-
methyl-2,4-dihydro[1,2,4]triazol-3-ones 8a–f based on the reac-
tion of 4-imino-N-arylimidazolidinones 7a–f with hydrazine.
The products obtained can be of interest as antemetic agents8 as
well as in the prevention and treatment of amyotrophic lateral
sclerosis.9
Figure 1 Fragments of the 2D 1H-13C HMBC spectrum (600 MHz, DMSO-d6)
of compound 8b.
cyclic system of iminoazolidinones 7 toward hydrazine. At the
present time the available experimental data do not allow us to
make the conclusion explaining the difference in the reactivity
between compounds 5 and 7, which can be the subject of our
further investigations.
The triazolones 8a–f are solid crystalline compounds whose
structures were confirmed by 1H and 13C NMR spectroscopy and
elemental analyses. The 1H NMR spectra of the products contain
characteristic signals of methylene protons at d 3.96–4.04 ppm
and substituted amino group protons at d 5.51–6.32 ppm. These
values are in good agreement with literature data.7
The structure of 4-methoxyphenylaminomethyltriazolone 8b
was proved by 15N NMR spectroscopy and HMBC experiments.
The H-13C HMBC spectrum contains cross-peaks between the
1
doublet of protons at C6 (d 3.96, J 5 Hz) and C1' (d 142.21), C4
References
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5 M. Sanudo, M. Garcia-Valverde, S. MarcacciniandT.Torroba, Tetrahedron,
5-(4-Chlorophenylaminomethyl)-2,4-dihydro[1,2,4]triazol-3-one 8c.
Yield 73%, mp 222–225°C. 1H NMR (DMSO-d6) d: 4.01 (d, 2H, CH2,
J 6 Hz), 6.16 (t, 1H, NH, J 6 Hz), 6.63 (d, 2H, HAr, J 8 Hz), 7.11 (d, 2H,
HAr, J 8 Hz), 11.26 (m, 2H, NH). 13C NMR (DMSO-d6) d: 39.6, 113.9,
120.1, 128.6, 145.9, 147.1, 156.3. Found (%): C, 48.34; H, 4.14; N, 25.09.
Calc. for C9H9ClN4O (%): C, 48.12; H, 4.04; N, 24.94.
5-(4-Fluorophenylaminomethyl)-2,4-dihydro[1,2,4]triazol-3-one 8d.
Yield 81%, mp 218–221°C. 1H NMR (DMSO-d6) d: 4.00 (d, 2H, CH2,
J 6 Hz), 5.89 (t, 1H, NH, J 6 Hz), 6.61 (m, 2H, HAr), 6.93 (m, 2H, HAr),
11.24 (s, 2H, NH). 13C NMR (DMSO-d6) d: 40.1, 113.4, 115.3, 144.8,
146.1, 153.3, 156.3, 156.4. Found (%): C, 52.14; H, 4.25; N, 27.07. Calc.
for C9H9FN4O (%): C, 51.92; H, 4.36; N, 26.91.
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5157.
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E. H. Hu, P. J. Manley, L. A. Neilson, L. R. Tehrani and Z. Wu, US Patent
WO 2005/100356, 2005.
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M. A. Cascieri, S. Sadowski, C. D. Strader, D. E. MacIntyre and J. M.
Metzger, J. Med. Chem., 1996, 39, 1760.
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4,044,021, 1977.
5-(3-Chlorophenylaminomethyl)-2,4-dihydro[1,2,4]triazol-3-one 8e.
Yield 75%, mp 231–233°C. 1H NMR (DMSO-d6) d: 4.04 (d, 2H, CH2,
J 5 Hz), 6.32 (t, 1H, NH, J 5 Hz), 6.61 (m, 3H, HAr), 7.09 (t, 1H, HAr
,
J 7 Hz), 11.29 (m, 2H, NH). 13C NMR (DMSO-d6) d: 39.3, 111.2, 111.7,
116.0, 130.3, 133.6, 145.7, 149.6, 156.2. Found (%): C, 47.91; H, 3.91;
N, 24.76. Calc. for C9H9ClN4O (%): C, 48.12; H, 4.04; N, 24.94.
5-(3-Methoxyphenylaminomethyl)-2,4-dihydro[1,2,4]triazol-3-one 8f.
Yield 67%, mp 204–205°C. 1H NMR (DMSO-d6) d: 3.66 (s, 3H, OMe),
4.00 (d, 2H, CH2, J 6 Hz), 5.94 (t, 1H, NH, J 6 Hz), 6.20 (m, 3H, HAr),
6.98 (t, 1H, HAr, J 7 Hz), 11.26 (m, 2H, NH). 13C NMR (DMSO-d6) d:
39.7, 54.7, 98.5, 102.1, 105.7, 129.6, 146.2, 149.5, 156.3, 160.3. Found (%):
C, 54.32; H, 5.60; N, 25.61. Calc. for C10H12N4O2 (%): C, 54.54; H, 5.49;
N, 25.44.
Received: 26th November 2013; Com. 13/4252
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