Interaction of 2-aryl-4-cyano-1,3-oxazole-5-sulfonyl chlorides with amidines

Article abstract of DOI:10.1134/S1070363213070165

Reaction of 4-cyano-1,3-oxazole-5-sulfonyl chlorides with amidines results in new 7-amino-1,3-oxazolo[5,4-d]pyrimidines. Their structure was confirmed by spectral methods and X-ray diffraction analysis.

Full text of DOI:10.1134/S1070363213070165

ISSN 1070-3632, Russian Journal of General Chemistry, 2013, Vol. 83, No. 7, pp. 1402–1405. © Pleiades Publishing, Ltd., 2013.
Original Russian Text © A.N. Kornienko, S.G. Pil’o, V.M. Prokopenko, E.B. Rusanov, V.S. Brovarets, 2013, published in Zhurnal Obshchei Khimii, 2013,
Vol. 83, No. 7, pp. 1151–1155.
Interaction of 2-Aryl-4-cyano-1,3-oxazole-5-sulfonyl Chlorides
with Amidines
A. N. Kornienko, S. G. Pil’o, V. M. Prokopenko, E. B. Rusanov, and V. S. Brovarets
Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine,
ul. Murmanskaya 1, Kyiv, 02660 Ukraine
e-mail: brovarets@bpci.kiev.ua
Received June 28, 2012
Abstract—Reaction of 4-cyano-1,3-oxazole-5-sulfonyl chlorides with amidines results in new 7-amino-1,3-
oxazolo[5,4-d]pyrimidines. Their structure was confirmed by spectral methods and X-ray diffraction analysis.
DOI: 10.1134/S1070363213070165
Recently, we have synthesized 4-cyano-1,3-
oxazole-5-sulfonyl chlorides I [1], which react with
piperidine or morpholine in dioxane in the presence of
triethylamine at reflux to afford the corresponding
sulfonamides. In this work it is shown that amidines
interact originally with compounds I to form 7-amino-
1,3-oxazolo[5,4-d] pyrimidines V in 44-60% yields
(Table 1).
due to the elimination of sulfur dioxide III → IV, and
the subsequent tautomerization IV → V. Also it is not
improbable that sulfonamides II react with another
molecule of amidine at the C5 atom of the ring or the
cyano group followed by the closure of the pyrimidine
ring by the nucleophilic substitution of the sulfonyl-
amide fragment. However, the fact that 4-cyano-1,3-
oxazoles containing sulfamide [1] or arylsulfonyl [2]
groups at the atom C5 do not react with amidines is an
indirect confirmation of the proposed scheme involve-
ing an intermediate formation of the seven-membered
structure III. It is noteworthy that desulfurization of
the products proceeds under mild conditions (at 20°C).
Synthesis of products Va–Vk includes several
steps: the initial formation of intermediates II, the
intramolecular cyclization II → III, the transformation
of the seven-membered ring to the six-membered ring
NH
C
N
CN
SO2Cl
HN
HN
NH
C
2Et3N
HCl
N
N
N
O
N
+
R
HCl
R
−2Et3N
R
Ar
Ar
H2N
Ar
O
NH
SO2
O
SO2
II
III
Iа, Ib
−SO2
NH
NH2
N
O
N
N
N
Ar
Ar
O
N
H
R
N
R
IV
Vа−Vk
R = Ph (Vа, Vh), 4-MeC6H4 (Vb), 4-EtC6H4 (Vc, Vi), 4-MeOC6H4 (Vd, Vj), 4-FC6H4 (Ve, Vk), 4-MeC6H4S (Vf), Me (Vg);
Ar = Ph (Iа, Vа–Vg), 4-MeC6H4 (Ib, Vh–Vk).
1402

INTERACTION OF 2-ARYL-4-CYANO-1,3-OXAZOLE-5-SULFONYL CHLORIDES
1403
Table 1. Yields, melting points and data of elemental analyses for compounds V
Found, %
Calculated, %
Comp.
no.
Yield, %
mp, °С
Formula
C
H
N
C
H
N
54
56
60
60
50
50
44
50
52
52
50
251–252
262–264
225–226
244–245
266–267
254–255
227–229
303–304
266–267
301–303
299–301
70.95
71.48
72.10
67.89
66.72
64.67
63.75
71.50
72.74
68.62
67.40
4.25
4.67
5.02
4.42
3.67
4.24
4.48
4.68
5.53
4.80
4.01
19.40
18.59
17.82
17.68
18.18
16.70
24.77
18.67
16.89
16.91
17.87
C17H12N4O
C18H14N4O
C19H16N4O
C18H14N4O2
C17H11FN4O
C18H14N4OSа
C12H10N4O
C18H14N4O
C20H18N4O
C19H16N4O2
C18H13FN4O
70.82
71.51
72.14
67.92
66.66
64.65
63.71
71.51
72.71
68.66
67.49
4.20
4.67
5.10
4.43
3.62
4.22
4.46
4.67
5.49
4.85
4.09
19.43
18.53
17.71
17.60
18.29
16.75
24.76
18.53
16.96
16.86
17.79
Vа
Vb
Vc
Vd
Ve
Vf
Vg
Vh
Vi
Vj
Vk
a Found, %: S 9.68. Calculated, %: S 9.59.
The target products were isolated in satisfactory yields.
This direction of the reaction is apparently due to the
formation of a thermodynamically stable pyrimidine
ring. It should also be noted that this contraction of the
heterocyclic fragment due to sulfur dioxide liberation
is well known [3, 4]. However, such transformations
are carried out under rigid conditions.
relative to the bicycle by 8.95(8) and 4.99(6)°, respec-
tively. The bond length С4–N3 is strongly reduced
compared to the value characteristic of the single С–N
bonds [1.338(2) Å]. The sum of bond angles at the
nitrogen atom of the amino group is 360(2)°, indicat-
ing the coupling of the lone electron pair of the
nitrogen atom N3 with the π-system of heterocycle. In
the crystal the formation is observed of weak intermole-
cular hydrogen bonds N3–H2···N4#1 and N3–H1···N2#2
with the following parameters: N3–H2 0.93(2),
N3···N4#1 3.148(3), N3–H2···N4#1 152.3(17)° и N3–H1
0.88(2), N3··N2#2 3.059(2), N3–H1···N2#2 144.7(19)°,
respectively, (symbols #1 and #2 denote the atoms that
are connected with the basic operations of symmetry
–x + 1, y, –z + 0.5 и x, –y, z – 0.5, respectively).
The IR spectra of compounds Va–Vk (Table 2)
contain the absorption bands of the stretching
vibrations of NH2-groups at 3314–3378 and 3208–
3220 cm–1 and the signals of 7-aminooxazolo-[5,4-d]-
1
pyrimidines moiety [5]. In the H NMR spectra along
with the signals of the protons of aromatic rings and
substituents there is a broad singlet of NH2-group at
7.66–7.87 ppm.
As compounds V are structural analogs of purine
bases and among them substances with diverse
biological activities were found [7–12], the developed
approach to the synthesis of 7-amino-1,3-oxazolo[5,4-
d]pyrimidines, which well supplements the well-
known methods for their preparation [5, 9, 13, 14],
deserves further studying, as will be discussed in
subsequent reports.
To establish unambiguously the structure of com-
pounds
V and to consider their spatial structure we carried
out XRD analysis of compound Ve (see figure).
Values of the bond lengths and bond angles of the
central bicyclic moiety are within the expected range
and are consistent with the structural formula of the
compound. Thus, the bonds themselves are delocalized
and have values typical of delocalized structures
previously studied, for example, for the related
compound containing a similar moiety [6]. The central
bicycle is flat, the atoms are out-of-plane only by
0.0044 Å. Phenyl rings С6–С11 and С12–С17 are turned
EXPERIMENTAL
The IR spectra were recorded on a Vertex 70
1
instrument from KBr pellets. The H and 13C NMR
spectra were obtained on a Bruker Avance DRX-500
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 83 No. 7 2013

1404
KORNIENKO et al.
Table 2. Spectral data of compounds V
Comp.
no.
IR spectrum (KBr), ν, cm–1
1Н NMR spectrum (DMSO-d6), δ, ppm
Mass-spectrum, m/z
289 [M + 1]+
3322, 3210 (NH2); 1637, 1592, 7.50–8.37 m (10Н, 2С6Н5), 7.83 br.s (2Н, NH2)
1392, 1316, 1275, 1130, 1048
Vа
Vb
Vcа
3326, 3212 (NH2); 1635, 1590, 2.37 s (3Н, СН3), 7.29 d, 8.26 d (4Н, С6Н4, J 8.0 Hz), 7.61 m, 8.15 m
1393, 1313, 1278, 1129, 1048
303 [M + 1]+
(5Н, С6Н5), 7.78 br.s (2Н, NH2)
3324, 3211 (NH2); 1637, 1588, 1.23 t (3Н, СН3, J 7.5 Hz), 2.68 q (2Н, СН2, J 7.5, J 1.5 Hz), 7.33 d,
317 [M + 1]+
1395, 1312, 1276, 1130, 1048
8.28 d (4Н, С6Н4, J 8.5 Hz), 7.63 m, 8.16 m (5Н, С6Н5), 7.79 br.s (2Н,
NH2)
Vdb
Vec
Vfd
Vg
Vh
Vi
3326, 3213 (NH2); 1634, 1607, 3.84 s (3Н, ОСН3), 7.04 d, 8.32 d (4Н, С6Н4, J 8.5 Hz), 7.63 m, 8.15
1395, 1304, 1253, 1131, 1048 m (5Н, С6Н5), 7.75 br.s (2Н, NH2)
319 [M + 1]+
307 [M + 1]+
335 [M + 1]+
227 [M + 1]+
303 [M + 1]+
331 [M + 1]+
333 [M + 1]+
321 [M + 1]+
3326, 3213 (NH2); 1637, 1593, 7.32 m, 8.40 m (4Н, С6Н4), 7.63 m, 8.15 m (5Н, С6Н5), 7.85 br.s (2Н,
1395, 1303, 1277, 1131, 1048 NH2)
3378, 3211 (NH2); 1626, 1599, 2.38 s (3Н, СН3), 7.29 d, 7.50 d (4Н, С6Н4, J 8.5 Hz), 7.57 m, 8.05 m
1346, 1307, 1276, 1133, 1045 (5Н, С6Н5), 7.87 br.s (2Н, NH2)
3314, 3220 (NH2); 1665, 1599, 2.44 s (3Н, СН3), 7.61 m, 8.10 m (5Н, С6Н5), 7.66 br.s (2Н, NH2)
1404, 1297, 1274, 1136, 1045
3320, 3209 (NH2); 1638, 1593, 2.43 s (3Н, СН3), 7.44 d, 8.06 d (4Н, С6Н4, J 8.5 Hz), 7.50 m, 8.37 m
1391, 1316, 1273, 1129, 1048
3322, 3208 (NH2); 1635, 1596, 1.20 t (3Н, СН3, J 7.5 Hz), 2.39 s (3Н, СН3), 2.66 q (2Н, СН2, J 7.5, J
1395, 1311, 1275, 1135, 1051 1.5 Hz), 7.32–8.30 m (8Н, 2С6Н4), 7.76 br.s (2Н, NH2)
3323, 3209 (NH2); 1635, 1608, 2.42 s (3Н, СН3), 3.84 s (3Н, ОСН3), 7.04–8.31 m (8Н, 2С6Н4),
1396, 1306, 1256, 1134, 1050 7.71 br.s (2Н, NH2)
(5Н, С6Н5), 7.81 br.s (2Н, NH2)
Vj
3326, 3212 (NH2); 1637, 1594, 2.42 s (3Н, СН3), 7.34–8.39 m (8Н, 2С6Н4), 7.82 br.s (2Н, NH2)
Vk
1395, 1304, 1235, 1131, 1050
13С NMR spectrum (DMSO-d6), δC, ppm: 15.78, 28.53, 115.03, 126.87, 127.24, 128.26, 128.38, 129.84, 132.14, 135.49, 146.73, 156.70,
a
b
158.49, 160.19, 165.78. 13С NMR spectrum (DMSO-d6), δC, ppm: 55.77, 114.22, 114.69, 126.90, 127.19, 129.82, 129.94, 130.42,
132.08, 156.65, 158.26, 160.03, 161.67, 165.81. 13С NMR spectrum (DMSO-d6), δC, ppm: 115.14, 115.69, 115.86, 126.80, 127.26,
c
129.84, 130.53, 130.60, 132.20, 134.38, 134.40, 156.72, 158.64, 159.12, 163.15, 165.12, 165.71. d 13С NMR spectrum (DMSO-d6), δC,
ppm: 21.36, 114.00, 126.57, 126.69, 127.10, 129.76, 130.32, 132.03, 135.64, 139.36, 156.46, 157.51, 165.10, 166.82.
spectrometer (500 and 125 MHz, respectively),
internal reference TMS. GC-MS spectra were recorded
using a high-performance liquid chromatograph-mass
spectrometer Agilent 1100 Series equipped with a
diode array with a mass selective detector Agilent
LC\MSD SL. Parameters of GC-MS analysis: column
Zorbax SB-C18 1.18 µm 4.6×15 mm (PN 821975-
932); solvent acetonitrile–water (95:5), 0.1% aqueous
trifluoroacetic acid, eluent flow 3 ml min–1, injection
volume 1 µl; UV detecting at 215, 254, 285 nm,
chemical ionization at atmospheric pressure (APCI),
scan range m/z 80–1000. Melting points were
measured on a Fisher-Johns instrument.
Single crystal X-ray diffraction analysis of
compound Ve was performed at room temperature on
a Bruker Smart Apex II diffractometer (λMoKα- radia-
tion, graphite monochromator, θmax 28.1°, crystal size
0.14×0.25×0.30 mm, spherical segment –25 ≤ h ≤ 41,
–9 ≤ k ≤ 8, –16 ≤ l ≤ 17). 11022 reflections were
collected, 3379 of which were independent (R-factor is
0.0403). The crystals of compound Ve are monoclinic,
C17H11FN4O, M 306.3, space group C2/c, а 31.366(3),
b 7.2159(5), c 10.9413(3) Å, β 103.406(7)°, V
2830.6(4) Å3, Z 8, dcalc 1.437, μ 0.103 mm–1, F(000)
1264. The structure was solved by the direct method
and refined by the least squares method using
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 83 No. 7 2013

INTERACTION OF 2-ARYL-4-CYANO-1,3-OXAZOLE-5-SULFONYL CHLORIDES
1405
0.01 mol of a 4-cyano-1,3-oxazole-5-sulfonyl chloride
I [1], 0.01 mol of the appropriate amidine hydro-
chloride, and 0.02 mol of triethylamine in 50 ml of
anhydrous tetrahydrofuran was stirred at 20–25°C for
48 h. The precipitate was filtered off, the solvent was
removed in a vacuum. The residue was treated with
water, filtered off, dried, and purified by recrystal-
lization from acetonitrile.
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lengths and angles: C1N1 1.330(2), C1N2 1.354(2), C2N2
1.324(2), C2C3 1.374(3), C3C4 1.397(2), C4N1 1.357(2),
C4N3 1.338(2), C3N4 1.390(2), C5N4 1.304(2), C2O1 1.373(2),
C5O1 1.386(2) Å; C1N1C4 119.79(16), N1C1N2 127.19(17),
C2N2C1 110.31(15), N2C2C3 129.29(17), C2C3C4 115.59(18),
N1C4C3 117.82(17), O1C2C3 107.18(16), C2C3N4 110.50(16),
C5N4C3 103.49(15), N4C5O1 114.74(16), C2O1C5 104.09(14),
N2C2O1 123.53(16), N4C3C4 133.89(18)°.
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