Reactions of 1,3,5-triazinyl-nitroformaldoximes. 1. Interaction of 1,3,5-triazinylnitroformaldoximes with dicarbonyl compounds

Article abstract of DOI:10.1007/s10593-009-0314-7

Addition of enolates of dicarbonyl compounds to 1,3,5-triazinylnitrile oxides, prepared in situ from 2-R-4-R¹-1,3,5-triazin-6- ylnitroformaldoximes, led to the formation of 3,4,5-trisubstituted isoxazoles. The X-ray crystal structure of 4-ethox

Full text of DOI:10.1007/s10593-009-0314-7

Chemistry of Heterocyclic Compounds, Vol. 45, No. 5, 2009
REACTIONS OF 1,3,5-TRIAZINYL-
NITROFORMALDOXIMES. 1. INTERACTION
OF 1,3,5-TRIAZINYLNITROFORMALDOXIMES
WITH DICARBONYL COMPOUNDS
V. V. Bakharev1*, E. V. Peresedova1, D. B. Krivolapov2,
E. V. Mironova2, and I. A. Litvinov2
Addition of enolates of dicarbonyl compounds to 1,3,5-triazinylnitrile oxides, prepared in situ from
2-R-4-R1-1,3,5-triazin-6-ylnitroformaldoximes, led to the formation of 3,4,5-trisubstituted isoxazoles.
The X-ray crystal structure of 4-ethoxycarbonyl-3-(2'-methoxy-5-methyl-4'-pyrrolidinyl-1,3,5-triazin-
6'-yl)-5-isoxazole is described.
Keywords: enolates of dicarbonyl compounds, 1,3,5-triazinylnitroformaldoximes, 1,3,5-triazinylnitrile
oxides, 3,4,5-trisubstituted isoxazoles.
Nitroformaldoximes (nitrolic acids) can be the sources of highly reactive nitrile oxides. Two routes are
used for the generation nitrile oxides: elimination of nitrous acid on heating nitroformaldoximes or
deprotonation in the presence of strong bases with subsequent elimination of a nitrite ion. Nitrile oxides formed
in situ may dimerize to furoxanes [1], undergo 1,3-dipolar cycloaddition with various dipolarophiles [2-4], and
add to various reagents (amines, alcohols) [5, 6]. The unique example of the reaction of nitrile oxides with the
enolates of acetyl- and benzoylacetone is described elsewhere [1].
We have studied the reactions of 2-R-4-R1-1,3,5-triazin-6-ylnitroformaldoximes 1a-f with acetylacetone
and ethyl acetoacetate in the presence of a base.
The reaction occurred in an aqueous medium in the presence of 2 mol of sodium hydroxide and finished
with the formation of 4-acetyl-5-methyl-3-(2-R-4-R1-1,3,5-triazin-6-yl)isoxazoles 2a-f and 4-ethoxycarbonyl-
5-methyl-3-(2-R-4-R1-1,3,5-triazin-6-yl)isoxazoles 3a-e with yields of 55-75%. The 1,3,5-Triazinylnitrile
oxides are formed by deprotonation of the nitroformaldoximes starting materials with subsequent loss of a
nitrite anion. In accordance with the attack of the carbanion of the dicarbonyl compound on the carbon atom of
the nitrile oxide and the oxygen atom of the nitrile oxide on the carbon atom of the acetyl group ring closure to
_______
* To whom correspondence should be addressed, e-mail: knil@sstu.smr.ru.
1Samara State Technical University, Samara 443100, Russia.
2A. E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Science Center of the Russian Academy of
Sciences, Kazan 420088, Republic of Tatarstan, Russia; litvinov@iorc.kpc.ru.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, 743-752, May, 2009. Original article
submitted March 13, 2008.
0009-3122/09/4505-0587©2009 Springer Science+Business Media, Inc.
587

the 3,4,5-trisubstituted isoxazole occurred by [3+2] cycloaddition. In the 1H NMR spectra of the isoxazoles 2a-f
and 3a-e the signal of the methyl group in position 5 of the isoxazole appears as singlet in the 2.64-2.74 ppm
range. The range of the absorptions of the carbonyl group in the isoxazoles 2a-f is found in the range
1677-1693 cm-1 and in the isoxazoles 3a-e in the 1720-1730 cm-1 interval.
R1
R1
O
+ NaOH
– NaNO2
N
N
N
N
Me
R2
R
N
C+
N
–
N
HC
O
R
N
OH
NO2
O
1 a–f
R2 = Me
R2 = CO2Et
R1
N
R1
N
N
COMe
Me
N
N
CO2Et
Me
R
R
N
N
O
N
O
2 a–f
3 a–e
1–3 a–e R = OMe; a R1 = OMe; b R1 = NMe2; c
;
R1 =
N
; f R = R1 = OPr-n
O
e R1 =
d R1 =
;
N
N
Thus 1,3,5-triazinylnitroformaldoximes, present as their synthetic equivalents the 1,3,5-triazinylnitrile
oxides, can be starting materials for the synthesis 3,4,5-trisubstituted isoxazoles with a 1,3,5-triazine ring at
position 3.
The structure of isoxazole 3c was confirmed by X-ray crystallography. The asymmetric part of the unit
cell of the crystal of compound 3c contains two independent molecules 3cA and 3cB (Fig. 1).
Fig. 1. Geometry of the Molecules of Compound 3c in the Crystal.
588

Table 1. Bond Lengths (d) in Compound 3c
Bond
d, Å
Bond
d, Å
O(21A)–C(20A)
O(22A)–C(20A)
O(22A)–C(23A)
C(23A)–C(24A)
C(2A)–N(14A)
C(2A)–N(3A)
C(2A)–N(1A)
C(4A)–N(3A)
C(4A)–N(5A)
C(4A)–C(7A)
1.198(5)
1.332(5)
1.509(6)
1.411(8)
1.325(4)
1.353(4)
1.354(4)
1.321(4)
1.321(4)
1.499(4)
1.316(4)
1.332(4)
1.342(4)
1.439(4)
1.293(5)
1.417(5)
1.357(5)
1.464(5)
1.334(5)
1.485(5)
1.419(4)
1.463(4)
1.465(4)
1.517(6)
1.499(6)
1.514(7)
N(5B)–C(4B)
1.329(4)
1.346(4)
1.326(4)
1.352(4)
1.310(4)
1.356(4)
1.490(4)
1.331(4)
1.329(4)
1.305(4)
1.420(4)
1.344(4)
1.365(4)
1.485(4)
1.469(5)
1.404(4)
1.204(4)
1.324(4)
1.460(6)
1.436(7)
1.437(4)
1.457(4)
1.466(7)
1.471(5)
1.495(6)
1.396(8)
N(5B)–C(6B)
N(3B)–C(4B)
N(3B)–C(2B)
N(1B)–C(6B)
N(1B)–C(2B)
C(4B)–C(7B)
C(6B)–O(12B)
C(2B)–N(14B)
C(7B)–N(8B)
C(6A)–N(1A)
C(6A)–O(12A)
C(6A)–N(5A)
O(12A)–C(13A)
C(7A)–N(8A)
C(7A)–C(11A)
C(11A)–C(10A)
C(11A)–C(20A)
C(10A)–O(9A)
C(10A)–C(19A)
O(9A)–N(8A)
N(14A)–C(15A)
N(14A)–C(18A)
C(15A)–C(16A)
C(18A)–C(17A)
C(16A)–C(17A)
C(7B)–C(11B)
C(10B)–O(9B)
C(10B)–C(11B)
C(10B)–C(19B)
C(11B)–C(20B)
O(9B)–N(8B)
C(20B)–O(21B)
C(20B)–O(22B)
O(22B)–C(23B)
C(23B)–C(24B)
C(13B)–O(12B)
C(15B)–N(14B)
C(15B)–C(16B)
C(18B)–N(14B)
C(18B)–C(17B)
C(16B)–C(17B)
The geometric parameters of molecules 3cA and 3cB differ very slightly: the bond lengths by 0.01-0.1 Å
(Table 1) and the valence angles by -0.1 to 2° (Table 2). The greatest differences are observed in the geometry of the
ethoxycarbonyl units at C(11A) and C(11B) of the isoxazole ring, especially for the torsion angles C(10)–C(11)–
C(20)–O(21) and C(20)–O(22)–C(23)–C(24) (Table 3). Yet another difference between molecules 3cA and 3cB is
connected with the conformation of the pyrrolidine ring. In molecule 3cA a twist conformation is formed (atoms
C(16) and C(17) are displaced by -0.361(5) and 0.202(5) Å respectively from the planar unit N(14)–C(15)–C(18))
while molecule 3cB has a C-envelope conformation (fragment N(14)–C(15)–C(17)–C(18) is planar within limits of
0.005(4) Å, while atom C(16) is displaced from the plane by -0.158(9) Å).
The triazine and isoxazole rings in molecules 3cA and 3cB are planar (triazine in 3cA within limits of
0.010(3), the triazine in 3cB within limits of 0.006(4), the isoxazole in 3cA within limits of 0.003(3), and the
isoxazole in 3cB within limits of 0.003(3) Å).The atoms of the methoxy group O(12)C(13) and the methyl atom
C(19) lie practically in the plane of the corresponding heterocycles. The bonds C(2A)–N(14A), C(2B)–N(14B),
C(6A)–O(12A), and C(6B)–O(12B) are strongly shortened (1.325-1.335 Å) which is a consequence of
conjugation of the unshared electron pairs of the heteroatoms with the π-system of the 1,3,5-triazine. The
dihedral angle between the planes of the triazine and isoxazole rings for molecules 3cA is 84.0(2)° and for
molecules 3cB is 64.1(2)°.
It should be noted that formation of classical hydrogen bonds is not possible, but there are interactions
of the type C-H···O both within and between molecules (parameters given in Table 4). Their aggregation leads to
–
the combination of 3c molecules into ribbons along the (11 ) direction of the crystal (Fig. 2).
1
589

Table 2. Valence Angles (ω) in Compound 3c
Angle
ω, deg
Angle
ω, deg
C(20A)–O(22A)–C(23A)
C(24A)–C(23A)–O(22A)
N(14A)–C(2A)–N(3A)
N(14A)–C(2A)–N(1A)
N(3A)–C(2A)–N(1A)
N(3A)–C(4A)–N(5A)
N(3A)–C(4A)–C(7A)
N(5A)–C(4A)–C(7A)
N(1A)–C(6A)–O(12A)
N(1A)–C(6A)–N(5A)
O(12A)–C(6A)–N(5A)
C(4A)–N(5A)–C(6A)
C(6A)–N(1A)–C(2A)
C(4A)–N(3A)–C(2A)
C(6A)–O(12A)–C(13A)
N(8A)–C(7A)–C(11A)
N(8A)–C(7A)–C(4A)
C(11A)–C(7A)–C(4A)
C(10A)–C(11A)–C(7A)
C(10A)–C(11A)–C(20A)
C(7A)–C(11A)–C(20A)
O(9A)–C(10A)–C(11A)
O(9A)–C(10A)–C(19A)
C(11A)–C(10A)–C(19A)
C(10A)–O(9A)–N(8A)
C(7A)–N(8A)–O(9A)
O(21A)–C(20A)–O(22A)
O(21A)–C(20A)–C(11A)
O(22A)–C(20A)–C(11A)
C(2A)–N(14A)–C(15A)
C(2A)–N(14A)–C(18A)
C(20B)–O(22B)–C(23B)
C(24B)–C(23B)–O(22B)
N(14B)–C(15B)–C(16B)
N(14B)–C(18B)–C(17B)
C(17B)–C(16B)–C(15B)
117.2(3)
106.9(5)
117.6(3)
118.2(3)
124.2(3)
128.4(3)
113.8(3)
117.8(3)
119.3(3)
127.2(3)
113.5(3)
112.3(3)
114.3(3)
113.6(3)
117.5(3)
112.3(3)
119.8(3)
127.7(3)
104.3(3)
131.4(3)
124.3(3)
109.3(3)
115.5(4)
135.1(4)
109.3(3)
104.8(3)
122.8(4)
123.9(4)
113.2(3)
124.4(3)
123.3(3)
117.4(3)
108.6(4)
103.5(3)
102.5(3)
110.5(4)
C(15A)–N(14A)–C(18A)
N(14A)–C(15A)–C(16A)
N(14A)–C(18A)–C(17A)
C(17A)–C(16A)–C(15A)
C(18A)–C(17A)–C(16A)
C(4B)–N(5B)–C(6B)
C(4B)–N(3B)–C(2B)
C(6B)–N(1B)–C(2B)
N(3B)–C(4B)–N(5B)
N(3B)–C(4B)–C(7B)
N(5B)–C(4B)–C(7B)
N(1B)–C(6B)–O(12B)
N(1B)–C(6B)–N(5B)
O(12B)–C(6B)–N(5B)
N(14B)–C(2B)–N(3B)
N(14B)–C(2B)–N(1B)
N(3B)–C(2B)–N(1B)
N(8B)–C(7B)–C(11B)
N(8B)–C(7B)–C(4B)
C(11B)–C(7B)–C(4B)
O(9B)–C(10B)–C(11B)
O(9B)–C(10B)–C(19B)
C(11B)–C(10B)–C(19B)
C(10B)–C(11B)–C(7B)
C(10B)–C(11B)–C(20B)
C(7B)–C(11B)–C(20B)
C(10B)–O(9B)–N(8B)
C(7B)–N(8B)–O(9B)
O(21B)–C(20B)–O(22B)
O(21B)–C(20B)–C(11B)
O(22B)–C(20B)–C(11B)
C(16B)–C(17B)–C(18B)
C(2B)–N(14B)–C(15B)
C(2B)–N(14B)–C(18B)
C(15B)–N(14B)–C(18B)
C(6B)–O(12B)–C(13B)
112.4(3)
102.2(3)
104.2(3)
104.8(3)
103.8(3)
112.6(3)
113.3(3)
114.3(3)
127.9(3)
117.0(3)
115.1(3)
119.6(3)
127.1(3)
113.2(3)
118.5(3)
116.7(3)
124.8(3)
112.2(3)
119.1(3)
128.5(3)
109.4(3)
115.7(3)
134.8(3)
103.8(3)
129.2(3)
126.8(3)
109.3(2)
105.3(3)
124.7(3)
123.7(3)
111.6(3)
109.8(4)
123.9(3)
123.7(3)
112.4(3)
118.2(3)
Packing of the molecules in the crystals of compound 3c is also stabilized by π-π interactions between
the triazine rings of molecule 3cA (parameters: distances between the centers of the rings dc 3.68Å, angles
between the rings α 0°, shortest distance between the planes of the angles d┴ 3.39Å, symmetry operation 1-x,
2-y, -z), and the triazine rings of molecule 3cB (parameters: dc 3.52 Å, α 0°, d┴ 3.33 Å, 1- x, -y, 1-z).
EXPERIMENTAL
1
IR spectra of KBr tablets were recorded on an Avatar 360ESP spectrometer. H NMR spectra were
recorded on Bruker AM-300 (300 MHz) and Bruker AC-200 (200 MHz) instruments in CDCl3 (compounds
2a,b, e, f and 3a-e) and DMSO-d6 solutions (compounds 2c,d) with TMS as internal standard.
590

Table 3. Torsion Angles (θ) in Compound 3c
Angle
θ, deg.
Angle
θ, deg.
C(20A)–O(22A)–C(23A)–C(24A)
N(3A)–C(4A)–N(5A)–C(6A)
C(7A)–C(4A)–N(5A)–C(6A)
N(1A)–C(6A)–N(5A)–C(4A)
O(12A)–C(6A)–N(5A)–C(4A)
O(12A)–C(6A)–N(1A)–C(2A)
N(5A)–C(6A)–N(1A)–C(2A)
N(14A)–C(2A)–N(1A)–C(6A)
N(3A)–C(2A)–N(1A)–C(6A)
N(5A)–C(4A)–N(3A)–C(2A)
C(7A)–C(4A)–N(3A)–C(2A)
N(14A)–C(2A)–N(3A)–C(4A)
N(1A)–C(2A)–N(3A)–C(4A)
N(1A)–C(6A)–O(12A)–C(13A)
N(5A)–C(6A)–O(12A)–C(13A)
N(3A)–C(4A)–C(7A)–N(8A)
N(5A)–C(4A)–C(7A)–N(8A)
N(3A)–C(4A)–C(7A)–C(11A)
N(5A)–C(4A)–C(7A)–C(11A)
N(8A)–C(7A)–C(11A)–C(10A)
C(4A)–C(7A)–C(11A)–C(10A)
N(8A)–C(7A)–C(11A)–C(20A)
C(4A)–C(7A)–C(11A)–C(20A)
C(7A)–C(11A)–C(10A)–O(9A)
C(20A)–C(11A)–C(10A)–O(9A)
C(7A)–C(11A)–C(10A)–C(19A)
C(20A)–C(11A)–C(10A)–C(19A)
C(11A)–C(10A)–O(9A)–N(8A)
C(19A)–C(10A)–O(9A)–N(8A)
C(11A)–C(7A)–N(8A)–O(9A)
C(4A)–C(7A)–N(8A)–O(9A)
C(10A)–O(9A)–N(8A)–C(7A)
C(23A)–O(22A)–C(20A)–O(21A)
92.8(6)
-1.5(5)
C(6B)–N(1B)–C(2B)–N(14B)
C(6B)–N(1B)–C(2B)–N(3B)
N(3B)–C(4B)–C(7B)–N(8B)
N(5B)–C(4B)–C(7B)–N(8B)
N(3B)–C(4B)–C(7B)–C(11B)
N(5B)–C(4B)–C(7B)–C(11B)
O(9B)–C(10B)–C(11B)–C(7B)
C(19B)–C(10B)–C(11B)–C(7B)
O(9B)–C(10B)–C(11B)–C(20B)
C(19B)–C(10B)–C(11B)–C(20B)
N(8B)–C(7B)–C(11B)–C(10B)
C(4B)–C(7B)–C(11B)–C(10B)
N(8B)–C(7B)–C(11B)–C(20B)
C(4B)–C(7B)–C(11B)–C(20B)
C(11B)–C(10B)–O(9B)–N(8B)
C(19B)–C(10B)–O(9B)–N(8B)
C(11B)–C(7B)–N(8B)–O(9B)
C(4B)–C(7B)–N(8B)–O(9B)
C(10B)–O(9B)–N(8B)–C(7B)
C(10B)–C(11B)–C(20B)–O(21B)
C(7B)–C(11B)–C(20B)–O(21B)
C(10B)–C(11B)–C(20B)–O(22B)
C(7B)–C(11B)–C(20B)–O(22B)
O(21B)–C(20B)–O(22B)–C(23B)
C(11B)–C(20B)–O(22B)–C(23B)
C(20B)–O(22B)–C(23B)–C(24B)
N(14B)–C(15B)–C(16B)–C(17B)
C(15B)–C(16B)–C(17B)–C(18B)
N(14B)–C(18B)–C(17B)–C(16B)
N(3B)–C(2B)–N(14B)–C(15B)
N(1B)–C(2B)–N(14B)–C(15B)
N(3B)–C(2B)–N(14B)–C(18B)
N(1B)–C(2B)–N(14B)–C(18B)
C(16B)–C(15B)–N(14B)–C(2B)
C(16B)–C(15B)–N(14B)–C(18B)
C(17B)–C(18B)–N(14B)–C(2B)
C(17B)–C(18B)–N(14B)–C(15B)
N(1B)–C(6B)–O(12B)–C(13B)
N(5B)–C(6B)–O(12B)–C(13B)
C(2B)–N(3B)–C(4B)–N(5B)
C(2B)–N(3B)–C(4B)–C(7B)
C(6B)–N(5B)–C(4B)–N(3B)
C(6B)–N(5B)–C(4B)–C(7B)
C(2B)–N(1B)–C(6B)–O(12B)
C(2B)–N(1B)–C(6B)–N(5B)
C(4B)–N(5B)–C(6B)–N(1B)
C(4B)–N(5B)–C(6B)–O(12B)
C(4B)–N(3B)–C(2B)–N(14B)
C(4B)–N(3B)–C(2B)–N(1B)
179.5(3)
-0.8(5)
177.9(3)
0.4(5)
-65.3(4)
113.8(4)
119.2(4)
-61.7(4)
-0.4(3)
-179.3(3)
-179.1(3)
1.3(5)
177.9(3)
-2.1(4)
177.8(4)
-175.2(3)
3.0(6)
0.7(5)
-178.7(3)
-178.8(3)
1.3(4)
0.5(4)
176.2(3)
175.5(3)
-8.8(5)
0.2(5)
179.9(3)
-94.2(4)
86.4(4)
80.9(4)
-98.6(4)
0.7(4)
0.3(4)
-178.3(3)
-0.3(4)
-176.5(3)
0.0(4)
157.1(4)
-16.6(5)
-22.3(5)
164.0(3)
-3.1(6)
-174.7(3)
-179.2(4)
5.4(6)
-0.6(4)
179.3(4)
175.5(5)
-4.6(8)
176.2(4)
165.4(5)
-10.6(9)
11.7(10)
-7.6(8)
0.3(5)
-176.6(4)
-0.5(5)
179.5(3)
-0.8(5)
175.3(3)
0.1(5)
2.6(5)
1.1(7)
-177.7(3)
-171.6(5)
5.6(6)
C(23A)–O(22A)–C(20A)–C(11A) 178.7(4)
C(10A)–C(11A)–C(20A)–O(21A) -171.3(4)
C(7A)–C(11A)–C(20A)–O(21A)
C(10A)–C(11A)–C(20A)–O(22A)
C(7A)–C(11A)–C(20A)–O(22A)
N(3A)–C(2A)–N(14A)–C(15A)
N(1A)–C(2A)–N(14A)–C(15A)
N(3A)–C(2A)–N(14A)–C(18A)
N(1A)–C(2A)–N(14A)–C(18A)
C(2A)–N(14A)–C(15A)–C(16A)
C(18A)–N(14A)–C(15A)–C(16A)
C(2A)–N(14A)–C(18A)–C(17A)
C(15A)–N(14A)–C(18A)–C(17A)
N(14A)–C(15A)–C(16A)–C(17A)
N(14A)–C(18A)–C(17A)–C(16A)
C(15A)–C(16A)–C(17A)–C(18A)
8.6(7)
11.2(7)
178.1(4)
0.9(5)
-168.9(4)
178.8(3)
-1.2(5)
1.9(5)
-178.9(3)
0.5(5)
-0.2(5)
179.4(3)
-0.1(5)
179.7(3)
-165.1(3)
14.1(4)
-179.0(3)
-179.7(3)
1.3(5)
-172.9(3)
8.0(4)
-0.9(5)
-30.5(4)
-26.8(5)
36.1(5)
-180.0(3)
179.7(3)
0.0(5)
591

Fig. 2. Ribbons of molecules 3c in the crystal, formed by C-H···O interactions. In the
diagram only those hydrogen atoms taking part directly in this interaction are shown.
Table 4. Interaction Parameters in the Crystal of Compound 3c
Symmetry
operation
DHA, deg.
D–H⋅⋅⋅A
D–H, Å
H⋅⋅⋅A, Å
D⋅⋅⋅A, Å
C(23A)–H(231)⋅⋅⋅O(22B)
C(24B)–H(245)⋅⋅⋅O(21A)
C(19B)–H(196)⋅⋅⋅O(22B)
0.97
0.96
0.96
2.59
2.57
2.44
3.551(6)
3.290(8)
3.035(5)
170.7
131.9
120.1
1 + x, y, z
—
—
X-ray Crystallographic Analysis of Crystals of Compound 3c were carried out on a Bruker Smart
APEX II CCD automatic diffractometer: graphite monochromator; λMoKα = 0.71073 Å; temperature 293 K;
absorption corrections were carried semiempirically on equivalent reflexions using the SADABS program [8].
Treatment of the initial mass of experimental intensity data was carried out with the SAINT Plus program [10].
The structure was solved by direct methods and refined by full-matrix least-squares analysis in F2 in the
anisotropic approximation for non-hydrogen atoms. All calculations were carried out using the SHELXTL
PLUS suite of programs [10]. Hydrogen atoms were placed in geometrically calculated positions and included in
the refinement in the "riding" model. All diagrams and analysis of intermolecular interactions were carried out
with the PLATON programs [11]. Atomic coordinates and structural parameters of compound 3c have been
deposited in the Cambridge Center for Crystal Structure Data (deposit no. CCDC 677330).
Crystals of compound 3c grown from acetone were colorless transparent prisms, triclinic, C15H19N5O4,
M
333.35, a = 8.6299(6), b = 11.9384(8), c = 16.774(1) Å, α = 89.504(1), β = 85.945(1), γ = 74.057(1)°, V = 1657.4(2) Å3,
d
calc = 1.34 g/cm3, Z = 4, space group P-1. Scanning angle 2.1 < θ< 26.0°. 6389 Independent reflections were measured,
5122 with I > 2σ(I). Calculations of absorptions were not carried out because they were so small, (µ(Mo) = 1.0 cm-1).
Final values of the divergence factors were Rob = 0.089 and Rwob = 0.254 for 5122 reflexions.
Investigations of a monocrystal of compound 3c were carried out in the X-ray Structural Section of the
Collective Analitical Center of the Physicochemical Investigation of the Structure, Properties, and Composition of
substances and Materials based on the A. E. Arbuzov Laboratory of Diffraction Methods of Investigation of Institute
of Organic and Physical Chemistry, Kazan Scientific Center of the Russian Academy of Sciences.
Compounds 1a-f were synthesized by method [12].
592

4-Acetyl-3-(4,6-dimethoxy-1,3,5-triazin-2-yl)-5-methylisoxazole (2a). Acetylacetone (2.05 ml,
2 mmol) was added with stirring to a solution of sodium hydroxide (1.6 g, 4 mmol) in water (20 ml) at 20-25°C,
and then compound 1a (2.46 g, 1 mmol) was added. The reaction mixture was kept at 20-25°C with stirring until
compound 1a had disappeared (TLC, 1-1.5 h). At the end of the reaction, the precipitate of compound 2a was
filtered off, washed with water (5 ml) and dried in the air. Yield 1.90 g (72%); mp 152-153°C. IR spectrum, ν,
cm-1: 3026, 2966, 1681, 1560, 1525, 1475, 1440, 1396, 1371, 1267, 1224, 1199, 1109, 1082, 1016, 1002, 975,
1
931, 860, 825, 769. H NMR spectrum, δ, ppm: 2.41 (3H, s, COCH3); 2.69 (3H, s, CH3); 4.11 (3H, s, OCH3).
Found, %: C 50.21; H 4.50; N 21.09. C11H12N4O4. Calculated, %: C 50.00; H 4.58; N 21.20.
4-Acetyl-3-(6-dimethylamino-4-methoxy-1,3,5-triazin-2-yl)-5-methylisoxazole (2b) was prepared
analogously from compound 1b (2.42 g, 1 mmol).Yield 1.80 g (65%); mp 101-102°C. IR spectrum, ν, cm-1:
3029, 2960, 2933, 2875, 1679, 1598, 1571, 1533, 1500, 1475, 1444, 1369, 1259, 1241, 1199, 1079, 1054, 1004,
950, 887, 817, 617. 1H NMR spectrum, δ, ppm: 2.35 (3H, s, COCH3); 2.67 (3H, s, CH3); 3.15 and 3.19 (6H, two
s, NCH3); 3.94 (3H, s, OCH3). Found, %: C 52.05; H 5.59; N 25.16. C12H15N5O3. Calculated, %: C 51.98;
H 5.45; N 25.26.
4-Acetyl-3-(4-methoxy-6-pyrrolidinyl-1,3,5-triazin-2-yl)-5-methylisoxazole (2c) was prepared
analogously from compound 1c (2.68 g, 1 mmol). Yield 2.06 g (68%); mp 113-115°C. IR spectrum, ν, cm-1:
3012, 2993, 2946, 2883, 1681, 1585, 1568, 1529, 1460, 1444, 1371, 1342, 1259, 1220, 1178, 1157, 1080, 1035,
1010, 966, 950, 891, 854, 819, 761, 619. 1H NMR spectrum, δ, ppm: 1.96 (6H, m, CH2); 2.37 (3H, s, COCH3);
2.64 (3H, s, CH3); 3.53 (4H, m, NCH2); 3.93 (3H, s, OCH3). Found, %: C 55.32; H 5.74; N 23.02. C14H17N5O3.
Calculated, %: C 55.44; H 5.65; N 23.09.
4-Acetyl-3-(4-methoxy-6-piperidino-1,3,5-triazin-2-yl)-5-methylisoxazole (2d) was prepared
analogously from compound 1d (2.82 g, 1 mmol). Yield 1.97 g (62%); mp 73-75°C. IR spectrum, ν, cm-1: 3012,
2995, 2958, 2921, 2862, 1679, 1577, 1529, 1463, 1442, 1369, 1294, 1259, 1238, 1215, 1124, 1087, 1024, 993,
1
950, 885, 817, 619. H NMR spectrum, δ, ppm: 1.59 (6H, m, CH2); 2.35 (3H, s, COCH3); 2.67 (3H, s, CH3);
3.70 (4H, m, NCH2); 3.92 (3H, s, OCH3). Found, %: C 56.85; H 6.12; N 22.15. C15H19N5O3. Calculated, %:
C 56.77; H 6.03; N 22.07.
4-Acetyl-3-(4-methoxy-6-morpholino-1,3,5-triazin-2-yl)-5-methylisoxazole (2e) was obtained
analogously from compound 1e (2.84 g, 1 mmol). Yield 2.39 g (75%); mp 120-122°C. IR spectrum, ν, cm-1:
3018, 2983, 2962, 2923, 2869, 1693, 1581, 1560, 1527, 1467, 1438, 1367, 1305, 1272, 1228, 1110, 1087, 1068,
1026, 989, 921, 889, 852, 817, 765, 630, 538. 1H NMR spectrum, δ, ppm: 2.34 (3H, COCH3); 2.66 (3H, s, CH3);
3.68 and 3.80 (8H, m, NCH2CH2O); 3.92 (3H, s, OCH3). Found, %: C 52.53; H 5.48; N 21.79. C14H17N5O4.
Calculated, %: C 52.66; H 5.37; N 21.93.
4-Acetyl-5-methyl-3-(4,6-di-n-propoxy-1,3,5-triazin-2-yl)isoxazole (2f) was prepared analogously
from compound 1f (2.85 g, 1 mmol). Yield 1.86 g (58%); mp 65-66°C. IR spectrum, ν, cm-1: 2971, 2929, 2881,
1677, 1670, 1560, 1521, 1485, 1452, 1419, 1380, 1359, 1332, 1299, 1245, 1211, 1139, 1110, 1089, 1066, 999,
952, 931, 879, 827, 765, 622, 534. 1H NMR spectrum, δ, ppm, (J, Hz): 1.03 (6H, t, J = 7.2, CH3); 1.84 (4H, m,
CH2); 2.40 (3H, s, COCH3); 2.69 (3H, s, CH3); 4.44 (4H, m, OCH2). Found, %: C 56.38; H 6.41; N 17.40.
C15H20N4O4. Calculated, %: C 56.24; H 6.29; N 17.49.
Ethyl 3-(4,6-dimethoxy-1,3,5-triazin-2-yl)-5-methylisoxazol-4-ylcarboxylate (3a). Ethyl aceto-
acetate (2.53 ml, 2 mmol) was added with stirring at 20-25°C to a solution of sodium hydroxide (1.6 g, 4 mmol)
in water (20 ml) and then compound 1a (2.46 g, 1 mmol) was added. The reaction mixture was kept at 20-25°C
with stirring until the initial compound 1a had disappeared (TLC, 1-1.5 h). At the end of the reaction, the
precipitate of compound 3a was filtered off, washed with water (5 ml) an dried in the air. Yield 1.62 g (55%);
mp 91-95°C. IR spectrum, ν, cm-1: 3035, 2985, 2964, 2883, 1727, 1554, 1529, 1492, 1467, 1450, 1400, 1355,
1346, 1267, 1240, 1217, 1193, 1107, 1068, 1020, 1006, 977, 939, 914, 860, 825, 788, 752, 692, 536, 478.
1H NMR spectrum, δ, ppm (J, Hz): 1.20 (3H, t, J = 6.9, CH3); 2.74 (3H, s, CH3); 4.10 (3H, s, OCH3); 4.23 (3H,
q, J = 6.9, OCH3). Found, %: C 48.93; H 4.95; N 19.12. C12H14N4O5. Calculated, %: C 48.98; H 4.80; N 19.04.
593

Ethyl 3-(4-methoxy-6-dimethylamino-1,3,5-triazin-2-yl)-5-methylisoxazol-4-ylcarboxylate (3b) was
prepared analogously from compound 1b (2.42 g, 1 mmol). Yield 2.30 g (75%); mp 111-113°C. IR spectrum, ν,
cm-1: 3031, 2995, 2964, 2929, 2877, 2806, 1730, 1591, 1498, 1473, 1457, 1415, 1363, 1268, 1244, 1201, 1130,
1
1109, 1080, 1055, 1024, 997, 917, 896, 840, 821, 790, 715, 675, 644, 540. H NMR spectrum, δ, ppm (J, Hz):
1.21 (3H, t, J = 6.8, CH3); 2.71 (3H, s, CH3); 3.22 (6H, s, NCH3); 3.99 (3H, s, OCH3); 4.24 (3H, q, J = 6.8,
OCH2). Found, %: C 50.69; H 5.70; N 22.83. C13H17N5O4. Calculated, %: C 50.81; H 5.58; N 22.79.
Ethyl 3-(4-methoxy-6-pyrrolidino-1,3,5-triazin-2-yl)-5-methylisoxazol-4-ylcarboxylate (3c) was
obtained analogously from compound 1c (2.68 g, 1 mmol). Yield 2.30 g (69%); mp 121-123°C. IR spectrum, ν,
cm-1: 2975, 2877, 1729, 1596, 1583, 1568, 1527, 1498, 1452, 1365, 1342, 1269, 1247, 1224, 1187, 1168, 1112,
1
1076, 1020, 999, 966, 914, 817, 790, 675. H NMR spectrum, δ, ppm (J, Hz): 1.21 (3H, t, J = 6.9, CH3); 1.98
(4H, m, CH2); 2.71 ((3H, s, CH3); 3.64 (4H, t, J = 7.2, NCH2); 3.99 (3H, s, OCH3); 4.23 (3H, q, J = 6.9, OCH2).
Found, %: C 53.94; H 5.70; N 21.13. C15H19N5O4. Calculated, %: C 54.05; H 5.75; N 21.01.
Ethyl 3-(4-methoxy-6-piperidino-1,3,5-triazin-2-yl)-5-methylisoxazol-4-ylcarboxylate (3d) was prepared
analogously from compound 1d (2.82 g, 1 mmol). Yield 2.28 g (61%); mp 83-85°C. IR spectrum, ν, cm-1: 3137,
2987, 2946, 2923, 2856, 1726, 1585, 1525, 1496, 1471, 1454, 1375, 1348, 1296, 1269, 1244, 1217, 1155, 1130,
1110, 1087, 1074, 1026, 987, 906, 881, 850, 817, 790, 742, 717, 684, 538, 497. 1H NMR spectrum, δ, ppm (J, Hz):
1.21 (3H, t, J = 7.0, CH3), 1.65 (6H, m, CH2); 2.70 (3H, s, CH3); 3.83 (4H, t, J = 6.0, NCH2); 3.98 (3H, s, OCH3);
4.22 (3H, q, J = 7.0, OCH2). Found, %: C 55.47; H 6.20; N 20.00. C16H21N5O4. Calculated, %: C 55.32; H 6.09;
N 20.16.
Ethyl 3-(4-methoxy-6-morpholino-1,3,5-triazin-2-yl)-5-methylisoxazol-4-ylcarboxylate (3e) was
prepared analogously from compound 1e (2.84 g, 1 mmol). Yield 2.31 g (66%); mp 94-96°C. IR spectrum, ν, cm-1:
3002, 2979, 2958, 2927, 2869, 2846, 1720, 1579, 1535, 1504, 1469, 1448, 1375, 1350, 1303, 1278, 1244, 1224,
1132, 1112, 1080, 1028, 993, 885, 850, 839, 817, 792, 738, 677, 632, 540. 1H NMR spectrum, δ, ppm (J, Hz): 1.23
(3H, t, J = 7.0, CH3); 2.70 (3H, s, CH3); 3.72 and 3.91 (8H, m, NCH2CH2O); 4.00 (3H, s, OCH3); 4.23 (3H, q,
J = 7.0, OCH2). Found, %: C 51.66; H 5.42; N 20.18. C15H19N5O5. Calculated, %: C 51.57; H 5.48; N 20.05.
This work was carried out with financial support from the Fund for the Promotion of National Science.
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594