Synthesis of the novel heterocyclic system 7,8-dihydroimidazo[1,2-c]-[1,3] oxazolo[4,5-e][1,2,3]triazine

Full text of DOI:10.1007/s10593-012-1157-1

Chemistry of Heterocyclic Compounds, Vol. 48, No. 9, December, 2012 (Russian Original Vol. 48, No. 9, September, 2012)
SYNTHESIS OF THE NOVEL HETEROCYCLIC
SYSTEM 7,8-DIHYDROIMIDAZO[1,2-c]-
[1,3]OXAZOLO[4,5-e][1,2,3]TRIAZINE
A. O. Gurenko1, O. V. Shablykin1, A. P. Kozachenko1, and V. S. Brovarets1*
Keywords: 2-(aroylaminocyanomethylene)imidazolidines, 7,8-dihydroimidazo[1,2-c][1,3]oxazolo[4,5-e]-
[1,2,3]triazine, cyclization.
The novel heterocyclic systems 7,8-dihydroimidazo[1,2-c][1,3]oxazolo[4,5-e]pyrimidine [1], 7,8-dihydro-
imidazo[1,2-c][1,3]thiazolo[4,5-e]pyrimidine [2], and 4,5,7,8-tetrahydroimidazol[1,2-c][1,3]thiazolo[4,5-e][1,3,2]-
diazaphosphinine [3] have been prepared from the 2-(aroylaminocyanomethylene)imidazolidines 1a-c [1].
We propose to use compounds 1a-c in the synthesis of another novel condensed heterocyclic system, in
which oxazole and imidazoline rings are annelated to a 1,2,3-triazine ring. The 2-(aroylaminocyano-
methylene)imidazolidines 1a-c were initially maintained for 1 h in trifluoroacetic acid, and the reaction mixture
was then treated with excess NaNO2 to give the 2-aryl-7,8-dihydroimidazo[1,2-c][1,3]oxazolo[4,5-e]-
[1,2,3]triazines 3a-c in 54-61% yields. Formation of compounds 3a-c evidently occurs via the intermediate
5-amino-1,3-oxazoles 2a-c, which take part in a diazotation reaction.
The composition and structure of the compounds 3a-c obtained were confirmed by elemental analysis,
chromato-mass spectrometry, and also by IR, 1H NMR, and 13C NMR spectroscopy.
HN
N
N
H
N
NaNO2
Ar
CF3CO2H
N
N
N
N
N
N
H
H
C
N
1a–c
O
O
Ar
NH2 . CF3CO2H
O
N
Ar
2a–c
3a–c
a Ar = Ph, b Ar = 4-MeC6H4, c Ar = 4-ClC6H4
Hence, successive treatments of 2-(aroylaminocyanomethylene)imidazolidines with trifluoroacetic acid
and sodium nitrite gave representatives of the novel 7,8-dihydroimidazo[1,2-c][1,3]oxazolo[4,5-e]-
[1,2,3]triazine system.
1
IR spectra were recorded on a Vertex 70 spectrometer for KBr pellets. H and 13C NMR spectra were
recorded on a Bruker Avance DRX-500 instrument (500 and 125 MHz, respectively) with TMS as internal
standard. Chromato-mass spectra were recorded on an Agilent 1100 high performance liquid chromatograph.
_______
*To whom correspondence should be addressed, e-mail: brovarets@bpci.kiev.ua.
1Institute of Bioorganic and Petrochemistry, Ukraine National Academy of Sciences, 1 Murmanska St., Kyiv
02660, Ukraine.
_______________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1524-1525, September, 2012.
Original article submitted April 27, 2012.
0009-3122/12/4809-1423©2012 Springer Science+Business Media New York
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The chromato-mass spectroscopy analysis parameters were: Zorbax SB-C18 column, 1.8 microns, 4.615 mm with
solvents A) MeCN–H2O 95:5, 0.1% CF3COOH or B) 0.1% aqueous CF3COOH; eluent flow 3 ml/min; injection
volume 1 l; UV detectors 215, 254, 285 nm; CI at atmospheric pressure. Elemental analysis was performed in
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the analytical laboratory of the Institute of Bioorganic and Petrochemistry, Ukraine National Academy of
Sciences. Melting points were performed on Fisher-Johns equipment.
Synthesis of Compounds 3a-c (General Method). One of the compounds 1a-c (1 mmol) was
dissolved in trifluoroacetic acid (10 ml). The mixture was stirred for 1 h at 15°C, NaNO2 (0.35 g, 5 mmol) was
then added, and stirring was continued for 20 min at 15°C. The trifluoroacetic acid was evaporated in vacuo and
the residue was dissolved in methanol (3 ml), diluted with water (50 ml), and basified with 10% aqueous NaOH
solution to pH ~ 8. The precipitate was filtered off, and compounds 3a-c were purified by reprecipitation from a
mixture of DMF and water (1:2).
2-Phenyl-7,8-dihydroimidazo[1,2-c][1,3]oxazolo[4,5-e][1,2,3]triazine (3a). Yield 0.15 g (61%).
Yellow powder, mp 211-212°C. IR spectrum, , cm-1: 1709, 1602, 1549, 1481, 1431, 1299, 1251, 1198.
1H NMR spectrum (DMSO-d6), , ppm (J, Hz): 4.03 (2Н, t, J = 8.7, СН2); 4.49 (2Н, t, J = 8.7, СH2); 7.56-7.74
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(3Н, m, H-3,4,5 Ph); 8.06-8.24 (2Н, m, H-2,6 Ph). C NMR spectrum (DMSO-d6), , ppm: 49.5; 52.5; 121.1;
125.5; 127.7; 130.0; 133.1; 146.9; 157.0; 161.8. Mass spectrum, m/z: 240.2 [M+Н]+. Found, %: С 60.18;
Н 3.78; N 29.31. C12H9N5O. Calculated, %: С 60.25; H 3.79; N 29.27.
2-(4-Methylphenyl)-7,8-dihydroimidazo[1,2-c][1,3]oxazolo[4,5-e][1,2,3]triazine (3b). Yield 0.14 g
(55%). Yellow powder, mp 250-251°C. IR spectrum, , cm-1: 1704, 1609, 1552, 1496, 1431, 1296, 1249, 1206.
1H NMR spectrum (DMSO-d6), , ppm (J, Hz): 2.43 (3Н, s, СН3); 4.02 (2Н, t, J = 9.6, СH2); 4.50 (2Н, t,
J = 9.6, СH2); 7.45 (2Н, d, J = 7.5, H Ar); 8.04 (2Н, d, J = 7.5, H Ar). 13C NMR spectrum (DMSO-d6), , ppm:
21.7; 49.5; 52.5; 121.1; 122.8; 127.7; 130.6; 143.6; 146.9; 160.0; 161.8. Mass spectrum, m/z: 254.3 [M+Н]+.
Found, %: С 61.54; Н 4.41; N 27.59. C13H11N5O. Calculated, %: С 61.65; Н 4.38; N 27.65.
2-(4-Chlorophenyl)-7,8-dihydroimidazo[1,2-c][1,3]oxazolo[4,5-e][1,2,3]triazine (3c). Yield 0.15 g
(54%). Yellow powder, mp 280-281°C (decomp.). IR spectrum, , cm-1: 1706, 1597, 1546, 1482, 1432, 1297,
1
1242, 1207. H NMR spectrum (DMSO-d6), , ppm (J, Hz): 4.03 (2Н, t, J = 8.9, СН2); 4.51 (2Н, t, J = 8.9,
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СН2); 7.71 (2Н, d, J = 7.6, H Ar); 8.15 (2Н, d, J = 7.6, H Ar). C NMR spectrum (CF3COOD), , ppm: 44.1;
51.7; 119.2; 120.5; 130.0; 130.1; 143.5; 149.9; 160.8; 168.6. Mass spectrum, m/z: 274.7 [M+Н]+. Found,
%: С 52.48; Н 2.99; Cl 12.90; N 25.51. C12H8ClN5O. Calculated, %: С 52.66; Н 2.95; Cl 12.75; N 25.59.
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