N-Substituted imines of hexafluoroacetone and methyl trifluoropyruvate in cyclocondensation with 2-aminobenzimidazole

Full text of DOI:10.1134/S1070363214030323

ISSN 1070-3632, Russian Journal of General Chemistry, 2014, Vol. 84, No. 3, pp. 602–604. © Pleiades Publishing, Ltd., 2014.
Original Russian Text © V.B. Sokolov, A.Yu. Aksinenko, 2014, published in Zhurnal Obshchei Khimii, 2014, Vol. 84, No. 3, pp. 518–520.
LETTERS
TO THE EDITOR
N-Substituted Imines of Hexafluoroacetone
and Methyl Trifluoropyruvate
in Cyclocondensation with 2-Aminobenzimidazole
V. B. Sokolov and A. Yu. Aksinenko
Institute of Physiologically Active Substances, Russian Academy of Sciences,
Severnyi proezd 1, Chernogolovka, Moscow oblast, 142432 Russia
е-mail: alaks@ipac.ac.ru
Received May 14, 2013
DOI: 10.1134/S1070363214030323
Cyclocondensation of N-substituted imines of
hexafluoroacetone and methyl trifluoropyruvate with
1,3-binucleophiles (e.g., 2-aminopyridines [1, 2], 2-
aminothiazolines [1, 3], 2-aminothiazoles [1], amidines
[4], N-substituted ureas [5, 6]) afforded trifluoro-
methyl-containing five- and six-membered heterocycles.
benzimidazol-2-yl)amino-2,2,2-trifluoro-1-trifluoro-
methylethyl]carbamate III. The latter was heated in
DMF at 90°C for 2 h to give 2,2-bis(trifluoromethyl)-
2,3-dihydro-1H-benzo[4,5]imidazo[1,2-a][1,3,5]tri-
azin-4-one IV in 74% yield (Scheme 1).
The cyclocondensation of methyl trifluoropyruvate
acylimines Va–Vd with 2-aminobenzodiazole I was
carried out without isolating adducts by heating an
equimolar mixture of reactants in DMF at 90°C for
2 h. The reaction products were N-(2-trifluoromethyl-
3-oxo-2,3-dihydro-1H-imidazo[1,2-a]benzimidazol-2-
yl)amides Va–Vd.
The present report concerns the cyclocondensation
of ethoxycarbonylimine of hexafluoroacetone II and
methyl trifluoropyruvate acylimines Va–Vd with 2-
aminobenzodiazole I, 1,3-binucleophile containing the
guanidine moiety. Imines II and Va–Vd reacted with
2-aminobenzodiazole I under heating. The reaction
proceeds through initial addition of binucleophile to
the highly electrophilic C=N bond and subsequent
heterocyclization with ethanol or methanol release.
Reaction of hexafluoroacetone ethoxycarbonylimine II
with 2-aminobenzodiazole I afforded ethyl [1-(1H-
The synthesized 2,2-bis(trifluoromethyl)-2,3-di-
hydro-1H-benzo[4,5]imidazo[1,2-a][1,3,5]triazin-4-one
IV and N-(2-trifluoromethyl-3-oxo-2,3-dihydro-1H-
imidazo[1,2-a]benzimidazol-2-yl)amides VIa–VId are
colorless crystalline substances. Their NMR spectra
Scheme 1.
O
C
CF3
CF3
N
NH2
+
N
OC2H5
N
H
I
II
O
CF3
N
N
N
NH
NH
CF3
C
OC2H5
NH
NH
_C2H5OH
CF3
CF3
N
H
O
IV
III
602

N-SUBSTITUTED IMINES OF HEXAFLUOROACETONE
603
Scheme 2.
O
CH3O(O)C
CF3
N
N
N
NH2
+
N
C
R
O
C
_CH3OH
NH
N
H
NH
CF3
VIa_VId
R
O
Va_Vd
I
V, VI: R = i-C3H7 (а), 3-CH3-C6H4 (b), 2-F-C6H4 (c), 4-F-C6H4 (d).
contained characteristic signals. The signal of CF3-
group in the 19F NMR spectrum of IV appears at
–2.16 ppm; in the case of compounds VIa–VId this
signal lies in the range of 1.83–2.66 ppm (Scheme 2).
266°C. 1Н NMR spectrum (DMSO-d6), δ, ppm: 0.77 d
(3H, Me, J 7.1 Hz), 0.90 d (3H, Me, J 7.1 Hz), 2.59 m
(1H, CH), 7.06–7.19 m (3H, CHAr), 7.43 t (1H, CHAr,
J 5.9), 10.11 s (1H, NH), 12.74 br.s (1H, NH). 19F
NMR spectrum (DMSO-d6): δF 1.83 ppm. Found, %: C
51.73; H 3.84; N 17.31. C17H13F3N4O2. Calculated, %:
C 51.55; H 4.02; N 17.17.
Hence the cyclocondensation of 2-amino-benzo-
imidazole with N-substituted imines of hexafluoro-
acetone and methyl trifluoropyruvate resulted in
trifluoromethyl-containing benzo[4,5]imidazo[1,2-a]-
[1,3,5]triazin-4-one and 2,3-dihydro-1H-imidazo-
[1,2-a]benzimidazol-2-ylamides.
3-Methyl-N-(2-trifluoromethyl-3-oxo-2,3-dihydro-
1H-imidazo[1,2-a]benzimidazol-2-yl)benzamide (VIb)
was obtained similarly. Yield 72%, mp 251–253°C. 1Н
NMR spectrum (DMSO-d6), δ, ppm: 2.07 s (3H, Me),
7.12–7.27 m (1H, CHAr), 7.30–7.38 m (1H, CHAr),
7.43–7.53 m (6H, CHAr), 10.75 s (1H, NH), 13.04 br.s
(1H, NH). 19F NMR spectrum (DMSO-d6): δF 2.20 ppm.
Found, %: C 57.62; H 3.32; N 15.18. C18H13F3N4O2.
Calculated, %: C 57.76; H 3.50; N 14.97.
Ethyl [1-(1H-benzimidazol-2-yl)amino-2,2,2-tri-
fluoro-1-trifluoromethylethyl]carbamate (III). To a
suspension of 5 mmol of compound I in 10 mL of
benzene was added 5 mmol of II while stirring at 20°C.
The reaction mixture was stirred for 1 h at 50°C, then
cooled, and evaporated. The residue was recrystallized
from hexane. Yield 1.6 g, 86%, mp > 300°C. 1Н NMR
spectrum (DMSO-d6), δ, ppm: 1.06 t (3H, Me, J 7.1 Hz),
3.94 q (2Н, СН2О, J 7.2 Hz), 6.78–6.91 m (2H, CHAr),
6.97–7.12 m (2H, CHAr), 6.38 (1H, NH), 8.36 (1H,
NH), 10.44 (1H, NH). 19F NMR spectrum (DMSO-d6):
δF 3.68 ppm. Found, %: C 42.38; H 3.49; N 15.31.
C13H12F6N4O2. Calculated, %: C 42.17; H 3.27; N
15.13.
N-(2-Trifluoromethyl-3-oxo-2,3-dihydro-1H-imi-
dazo[1,2-a]benzimidazol-2-yl)-2-fluorobenzamide (VIc)
was prepared similarly. Yield 69%, mp 230–232°C. 1Н
NMR spectrum (DMSO-d6), δ, ppm: 6.86–7.15 m (5H,
CHAr), 7.19–7.42 m (3H, CHAr), 10.59 s (1H, NH),
19
12.85 br.s (1H, NH). F NMR spectrum (DMSO-d6),
δF, ppm: 2.12 (3F, CF3), from –35.53 to –35.60 m (1F,
CFAr). Found, %: C 53.72; H 2.42; N 14.60.
C17H10F4N4O2. Calculated, %: C 53.98; H 2.66; N 14.81.
2,2-Bis(trifluoromethyl)-2,3-dihydro-1H-benzo-
[4,5]imidazo[1,2-a][1,3,5]triazin-4-one (IV). A solu-
tion of 5 mmol of compound III in 10 mL of DMF
was heated for 2 h at 90°C, then cooled, and poured
into 50 mL of water. The precipitate was recrystallized
from 50% EtOH. Yield 1.2 g, 74%, mp 304–306°C. 1Н
NMR spectrum (DMSO-d6), δ, ppm: 6.90–7.18 m (3H,
CHAr), 7.70 d (1Н, CHAr, J 7.7 Hz), 9.92 s (1H, NH),
11.81 (1H, NH). 19F NMR spectrum (DMSO-d6): δF
–2.16 ppm. Found, %: C 40.58; H 1.66; N 17.51.
С11H6F6N4O. Calculated, %: C 40.76; H 1.87; N 17.28.
N-(2-Trifluoromethyl-3-oxo-2,3-dihydro-1H-imi-
dazo[1,2-a]benzimidazol-2-yl)-4-fluorobenzamide
(VId) was prepared similarly. Yield 72 %, mp 269–
1
271°C. Н NMR spectrum (DMSO-d6), δ, ppm: 7.08–
7.20 m (2H, CHAr), 7.22–7.37 m (3H, CHAr), 7.41–
7.49 m (1H, CHAr), 7.82–7.98 m (1H, CHAr), 10.54 s
(1H, NH), 12.74 br.s (1H, NH). 19F NMR spectrum
(DMSO-d6), δF, ppm: 2.66 s (3F, CF3), from –28.76 to
–29.06 m (1F, CFAr). Found, %: C 53.70; H 2.41; N
14.64. C17H10F4N4O2. Calculated, %: C 53.98; H 2.66;
N 14.81.
N-(2-Trifluoromethyl-3-oxo-2,3-dihydro-1H-imi-
dazo[1,2-a]benzimidazol-2-yl)isobutyramide (VIa)
was prepared similarly. Yield 1.2 g, 76%, mp 264–
1H and 19F NMR spectra were recorded on a Bruker
DPX 200 spectrometer at 200.13 and 188.29 MHz,
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 84 No. 3 2014

604
SOKOLOV, AKSINENKO
respectively, internal reference TMS or external
reference CF3COOH. Melting points were determined
in glass capillaries. Hexafluoroacetone ethoxycarbo-
nylimine II and N-substituted imines of methyl
trifluoropyruvate Va–Vd were prepared by procedure
in [7]. 2-Aminobenzimidazole I (Aldrich) was used
without further purification.
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ACKNOWLEDGMENTS
This work was financially supported by the
Program of Department of Chemistry and Materials
Science of the Russian Academy of Sciences
“Development of methods for chemicals and new
materials” and “Medical and Biomedical Chemistry”
and the Russian Foundation for Basic Research (grant
no. 11-03-00496-a).
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 84 No. 3 2014