Recyclization during trifluor-acetylation of 2-phenacyl-1H-benzimidazole benzoylhydrazone [3]

Full text of DOI:10.1023/A:1023987431842

Chemistry of Heterocyclic Compounds, Vol. 39, No. 3, 2003
RECYCLIZATION DURING TRIFLUOR-
ACETYLATION OF 2-PHENACYL-1H-
BENZIMIDAZOLE BENZOYLHYDRAZONE
I. B. Dzvinchuk and M. O. Lozinskii
Keywords: benzimidazoles, hydrazones, pyrazoles, trifluoroacetic anhydride, recyclization.
We have already shown that the acylation of arylhydrazones of 2-phenacyl-1H-benzimidazole by aroyl
chlorides is directed at a heterocyclic nitrogen atom with recyclization to give 5-(2-acylaminoanilino)-1-
arylpyrazoles [1]. Benzoylhydrazone 1, which is a structural analog of the abovementioned arylhydrazones,
reacts nonselectively with aroyl chlorides, according to our findings, to give product mixtures that prove
difficult to separate into pure compounds. However, the reaction of 1 with trifluoroacetic anhydride has
preparative value and proceeds with recyclization to give 1-benzoyl-5-[(2-trifluoroacetylamino)anilino]-3-
phenylpyrazole (2). This reaction is not complicated by acylotropy in the pyrazole ring, which is characteristic
for 5-anilino-1-benzoylpyrazoles [2].
CF3C=O
CF3C=O
N
H
H
N
H
N
Ph
(CF3CO)2O
dioxane,
N
N
H
N
N
N
Ph
Ph
15–20 oC, 1 h
PhCONH
N
COPh
PhCONH
N
1
CF3
NHCOCF3
Ph
Ph
N
N
(HOCH2)2
N
H
N
N
H
N
∆, 20 min
N
O
2
3
Ph
N2H4
MeOH,
∆, 30 min
NH2
Ph
N
H
NH
N
4
__________________________________________________________________________________________
Institute of Organic Chemistry, National Academy of Sciences of Ukraine, 02094 Kiev, Ukraine; e-mail:
iochkiev@ukrpack.net. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 436-437, March,
2003. Original article submitted January 13, 2003.
390
0009-3122/03/3903-0390$25.00©2003 Plenum Publishing Corporation

A necessary condition for recyclization is intramolecular addition of the benzoylamino group, which is a
weak nucleophile, to the benzimidazole C=N bond. The electrophilicity of the C=N bond is enhanced to the
required level by introducing the strongly electron-withdrawing trifluoroacetyl group at N(1).
The structure of 2 was confirmed by two transformations. Heating in ethyleneglycol at reflux leads to
alcoholysis of the benzoyl group and intramolecular cyclocondensation to give 1-(3-pyrazolyl)-2-
trifluoromethylbenzimidazole 3. Hydrazinolysis removes the benzoyl and trifluoroacetyl groups to give
anilinopyrazole 4 described by Essai and Salem [3]. The spectral parameters of these compounds are in accord
with the reported indices for their structural analogs [1, 2, 4] and the data of Essai [3].
1-Benzoyl-3-phenyl-5-[(2-trifluoroacetylamino)anilino]pyrazole (2). A sample of trifluoroacetic
anhydride (6 mmol) was added to a solution of 1 (5 mmol) in anhydrous dioxane (2.5 ml). The mixture was
stirred for 2-3 min until homogeneous and left for 1 h at 15-20°C. Then, 2-propanol (2.5 ml) and water (2.5 ml)
were added with stirring. After 20 min, the precipitate was filtered off and washed with 2-propanol to give 1.30
g (58%) of compound 2 as yellow crystals; mp 161-162°C (2-propanol–water, 3:1). IR spectrum (KBr), ν, cm-1:
1
1670, 1695 (C=O), 3285 (N–H). H NMR spectrum (300 MHz, DMSO-d6, TMS as the internal standard),
δ, ppm (J, Hz): 6.70 (1H, s, 4-H); 7.20 (1H, t, J = 7.2, 4-H, 1,2-C6H4); 7.40-7.50 (5H, m, m- and p-protons Ph +
5- and 6-H 1,2-C6H4); 7.60 (2H, t, J = 7.8, m-protons COPh); 7.71 (1H, t, J = 7.8, p-protons COPh); 7.78 (1H, d,
J =7.2, 3-H 1,2-C6H4); 7.88-7.90 (2H, m, o-protons Ph); 8.10 (2H, d, o-protons COPh); 9.51 (1H, s, NHHet);
11.33 (1H, s, NHCO). Found, %: C 64.12; H 3.97; F 12.79; N 12.38. C24H17F3N4O2. Calculated, %: C 64.00;
H 3.80; F 12.65; N 12.44.
1-(5-Phenyl-3-pyrazolyl)-2-trifluoromethyl-1H-benzimidazole (3). A solution of 2 (2 mmol) in
ethyleneglycol (2 ml) was heated at reflux for 20 min. Then, 2-propanol (0.5 ml) and water (0.5 ml) were added
and stirred until the onset of crystallization. After cooling, the precipitate was filtered off and washed with 1:1
water–2-propanol to give 0.45 g (68%) of compound 3 as colorless crystals; mp 148-149.5°C (water–
2-propanol, 3:1). 1H NMR spectrum (300 MHz, DMSO-d6, TMS as the internal standard), δ, ppm, J (Hz): 7.16
(1H, s, 4'-H); 7.42-7.56 (6H, m, 4-, 5-, 6-H + p- and m-protons Ph); 7.87 (2H, d, J = 7.5, o-protons Ph); 7.96
(1H, d, J = 6.3, 7-H); 13.96 (1H, s, NH). Found, %: C 62.32; H 3.47; F 17.28; N 16.95. C17H11F3N4.
Calculated, %: C 62.20; H 3.38; F 17.36; N 17.07.
3-(2-Aminoanilino)-5-phenylpyrazole (4). A solution of 2 (2 mmol) and 80% hydrazine (18 mmol)
hydrate in methanol (2 ml) was heated at reflux for 30 min. The solution was evaporated to half volume and an
equal volume of water was added. The mixture was stirred. After cooling, the precipitate was filtered off and
washed with 1:1 water–methanol to give 0.48 g (96%) of compound 4 as colorless crystals; mp 135-136.5°C
1
(mp 142-144°C [3]). H NMR spectrum (300 MHz, DMSO-d6, TMS as the internal standard), δ, ppm, J (Hz):
4.78 (2H, br. s, NH2); 6.21 (1H, s, 4-H); 6.53 (1H, t, J = 7.8, 5-H 1,2-C6H4); 6.61-6.68 (2H, m, 3- and 4-H
1,2-C6H4); 6.12 (1H, s, NHHet); 7.30-7.45 (4H, m, p- and m-protons Ph + 6-H 1,2-C6H4); 7.72 (2H, d, J = 7.8,
o-protons Ph); 12.38 (1H, br. s, 1-H).
REFERENCES
1.
2.
I. B. Dzvinchuk, A. V. Vypirailenko, and M. O. Lozinskii, Zh. Org. Khim., 33, 116 (1997).
I. B. Dzvinchuk, S. A. Kartashov, A. V. Vypirailenko, and M. O. Lozinskii, Khim. Geterotsikl. Soedin.,
703 (2002).
E. M. Essai and M. Salem, Bull. Soc. Chem. Belges, 94, 755 (1985).
I. B. Dzvinchuk, A. V. Vypirailenko, E. B. Rusanov, A. N. Chernega, and M. O. Lozinskii, Zh. Obshch.
Khim., 69, 856 (1999).
3.
4.
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