Novel variant of the anrorc rearrangement of [1,2,4]triazolo[1,5-a] pyrimidines and pyrimido-[1,2-a]benzimidazole

Full text of DOI:10.1007/s10593-012-0910-9

Chemistry of Heterocyclic Compounds, Vol. 47, No. 10, January, 2012 (Russian Original Vol. 47, No. 10, October, 2011)
NOVEL VARIANT OF THE ANRORC REARRANGEMENT
OF [1,2,4]TRIAZOLO[1,5-a]PYRIMIDINES AND PYRIMIDO-
[1,2-a]BENZIMIDAZOLE
A. Yu. Potapov1, P. S. Romanov1, Kh. S. Shikhaliev1*,
E. V. Polunin2, and S. I. Firgang2
Keywords: 3-acetyl-4-hydroxypyrimido[1,2-a]benzimidazole, 2-R-6-acetyl-7-hydroxy[1,2,4]triazolo-
[1,5-a]pyrimidine, 2-R-6-ethoxycarbonyl-7-methyl[1,2,4]triazolo[1,5-a]pyrimidine, 2-R-7-methyl-
[1,2,4]triazolo[1,5-a]pyrimidine-6-carboxylic acid, nucleophilic rearrangement.
Only isolated examples are described in literature for nucleophilic rearrangements involving
azolopyrimidines [1, 2]. In studying the alkaline hydrolysis reaction of 2-R-6-ethoxycarbonyl-7-methyl-
[1,2,4]triazolo[1,5-a]pyrimidine esters 1 we have found such a rearrangement in a pyrimidine ring which results
in the formation of the 2-R-6-acetyl-7-hydroxy[1,2,4]triazolo[1,5-a]pyrimidines 2a,b rather than the expected
2-R-7-methyl[1,2,4]-triazolo[1,5-a]pyrimidine-6-carboxylic acids 3a,b.
By contrast to the 1H NMR spectra of compounds 1a,b the spectra of compounds 2a,b show the absence
of the signals for the ethoxy group protons and the presence of strongly broadened signals for hydroxyl group
Me
O
N
N
N
OEt
R
N
1a,b
HO–, H2O
OH
N
O
Me
N
O
N
N
N
N
N
Me
N
OH
R
R
2a,b
3a,b
1–3 a R = H, b R = CF3
_______
*To whom correspondence should be addressed, e-mail: chocd261@chem.vsu.ru.
1Voronezh State University, 1 University Sq., Voronezh 394006, Russia.
2N. D. Zelinsky Institute for Organic Chemistry, 47 Leninsky Ave., Moscow 119991, Russia; e-mail:
ep507@mail.ru.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1578-1580, October, 2011.
Original article submitted July 19, 2011.
0009-3122/12/4710-1309©2012 Springer Science+Business Media, Inc.
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protons. The 1H–1H NOESY spectra show correlated peaks for the protons of the CH3 group and the pyrimidine
ring and this is impossible for the structures 3a,b. The 13C NMR spectra contain signals for the carbonyl carbon
and the C(7)OH carbon atom.
It is proposed that the reaction occurs via an ANRORC mechanism. The carbanion A formed as a result
of the addition of hydroxide ion is converted to the alcoholate ion B which recyclizes via the related
intermediates C and D to give the rearrangement products 2a,b.
OH
O
O
Me
N
O
H
Me
–
–
N
N
HO
OEt
N
N
OEt
1a,b
R
R
N
N
N
A
B
O
N
O
O
O
EtO
H
Me
H
N
Me
N
OEt
–
N
N
–
EtO
R
R
2a,b
N
N
N
C
D
Similarly, treatment of ethyl 4-methylpyrimido[1,2-a]benzmidazole-3-carboxylate (4) with aqueous
1
alkali gave 1-(4-hydroxypyrimido[1,2-a]benzimidazol-3-yl)ethanone (5) in whose H–1H NOESY spectrum
there are also cross peaks for the methyl and pyrimidine protons. The structures of all the compounds obtained
were also confirmed by their elemental analytical and mass spectrometric data.
O
O
OEt
Me
Me
HO
HO –, H2O
N
N
N
N
N
N
4
5
1
1H NMR, 13C NMR, and H–1H NOESY spectra were recorded on a Bruker DRX-500 spectrometer
(500 MHz) using DMSO-d6 with TMS as internal standard. Mass spectra were recorded on an LKB-9000
spectrometer with electron ionization energy 70 eV. Elemental analysis was carried out on a Carlo Erba
NA-1500 instrument. Melting points were determined using a Koffler block. The starting compounds 1a,b and 4
were prepared by the method reported in [3].
2-R-6-Acetyl-7-hydroxy[1,2,4]triazolo[1,5-a]pyrimidines 2a,b and 3-Acetyl-4-hydroxypyrimido-
[1,2-a]benzimidazole (5) (General Method). A mixture of 8% NaOH (10 ml) and compound 1a,b, or 4
(2 mmol) was heated with stirring to 80ºC and cooled to 0ºC. The precipitated sodium salt of product 2a,b, or 5
was filtered off, washed with iced water, suspended in a 10% solution of hydrochloric acid, filtered, and washed
with water.
1-(7-Hydroxy[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)ethanone (2a). Yield 2.2 g (62%); mp 232-235ºC.
1H NMR spectrum, , ppm: 2.58 (3H, s, CH3); 8.37 (1H, s, H-2); 8.54 (1H, s, H-5); 12.40-15.70 (1H, br. s, OH).
Mass spectrum, m/z (Irel, %): 178 [M]+ (100). Found, %: C 47.54; H 3.48; N 31.44. C7H6N4O2. Calculated, %:
C 47.19; H 3.39; N 31.45.
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1-(7-Hydroxy-2-trifluoromethyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)ethanone (2b). Yield 3.8 g
1
(77%); mp 218-220ºC. H NMR spectrum, , ppm: 2.60 (3H, s, CH3); 8.67 (1H, s, H-5); 9.35-13.73 (1H, br. s,
OH). Mass spectrum, m/z (Irel, %): 246 [M]+ (100). Found, %: C 38.77; H 2.11; N 22.59. C8H5F3N4O2.
Calculated, %: C 39.04; H 2.05; N 22.76.
1-(4-Hydroxypyrimido[1,2-a]benzimidazol-3-yl)ethanone (5). Yield 3.9 g (85%); mp > 240ºC (subl.).
1H NMR spectrum, , ppm: 2.59 (3H, s, CH3); 7.43 (1H, m); 7.55 (1H, m); 7.61 (1H, m) and 8.53 (1H, m,
H-6,7,8,9); 8.54 (1H, s, H-2); 13.70-13.84 (1H, br. s, OH). Mass spectrum, m/z (Irel, %): 227 [M]+ (100). Found, %:
C 63.82; H 4.06; N 18.28. C12H9N3O2. Calculated, %: C 63.43; H 3.99; N 18.49.
This work was carried out with the support of the Federal Target Program "Scientific and scientific-
pedagogical personnel of innovative Russia" in 2009-2013, state contract No. 14.740.11.036; the Ministry of
Education and Science of Russian Federation Analytical Target Program "Development of the higher school
scientific potential (2009-2011 years)", project No. 2.1.1/11994; and the Russian Federal Target Program for
Research & Development in Priority Fields for the Development of Russia's S&T Complex for 2007–2013, state
contract No. 16.512.11.2205.
REFERENCES
1.
2.
3.
S. Chimichi, B. Cocimelli, F. Bruni, S. Selleri, A. Constanzo, G. Guerrini, and G. Valle, J. Chem. Soc.,
Perkin Trans. 2, 1657 (1994).
A. Yu. Potapov, E. L. Polukhin, A. L. Sabynin, A. S. Shestakov, and Kh. S. Shikhaliev, Voronezh State
University Reports, Series Chemistry, Biology, Pharmacy [in Russian], No. 2, 31 (2010).
D. V. Kryl'skii, Kh. S. Shikhaliev, and A. Yu. Potapov, Izv. Vuzov. Khimiya i Khim. Tekhnologiya, 48,
No. 6, 72 (2005).
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