Thermolysis of 1-(methylideneamino)-1H-pyrrole-2,3-diones. Synthesis of pyrazolooxazines by [4 + 2]-cycloaddition of azomethine imines to alkenes

Article abstract of DOI:10.1134/S1070428017100086

Thermolysis of methyl 3-acyl-1-[(diphenylmethylidene)amino]-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates generates 4-acyl-1-(diphenylmethylidene)-3-(methoxycarbonyl)-1H-pyrazol-1-ium-5-olates which react with alkenes to give methyl 3-acyl-7,7-diphenyl-

Full text of DOI:10.1134/S1070428017100086

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2017, Vol. 53, No. 10, pp. 1531–1536. © Pleiades Publishing, Ltd., 2017.
Original Russian Text © V.E. Zhulanov, M.V. Dmitriev, A.N. Maslivets, 2017, published in Zhurnal Organicheskoi Khimii, 2017, Vol. 53, No. 10,
pp. 1504–1508.
Thermolysis of 1-(Methylideneamino)-1H-pyrrole-2,3-diones.
Synthesis of Pyrazolooxazines by [4+2]-Cycloaddition
of Azomethine Imines to Alkenes
V. E. Zhulanov, M. V. Dmitriev, and A. N. Maslivets*
Perm State National Research University, ul. Bukireva 15, Perm, 614990 Russia
*e-mail: koh2@psu.ru
Received April 26, 2017
Abstract—Thermolysis of methyl 3-acyl-1-[(diphenylmethylidene)amino]-4,5-dioxo-4,5-dihydro-1H-pyrrole-
2-carboxylates generates 4-acyl-1-(diphenylmethylidene)-3-(methoxycarbonyl)-1H-pyrazol-1-ium-5-olates
which react with alkenes to give methyl 3-acyl-7,7-diphenyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-
carboxylates. The product structure was confirmed by X-ray analysis.
DOI: 10.1134/S1070428017100086
Oxazine and oxadiazine rings are structural
fragments of many biologically active compounds.
Examples are the natural antibiotic oxazinomycin ac-
tive against Ehrlich ascite carcinoma [1], experimental
antitubercular drug pretomanid (PA-824) [2], selective
insecticide of the neonicotinoid series thiamethoxam
which is low toxic for mammalians [3], non-benzo-
diazepine anxiolytic etifoxine which is superior to
benzodiazepine analogs in efficiency [4], and anti-HIV
drug efavirenz [5].
amino]-1H-pyrrole-2,3-diones [6]. With the goal of
estimating the scope of this reaction, in the present
work we used ethyl vinyl ether, styrene, and 3,4-dihy-
dro-2H-pyran as dipolarophiles.
Methyl 4-aryl(alkyl)[2-(diphenylmethylidene)hy-
drazinyl]-4-oxobut-2-enoates 1a–1d reacted with
oxalyl chloride in anhydrous chloroform at 60–65°C
for 90–100 min to give methyl 3-acyl-1-[(diphenyl-
methylidene)amino]-4,5-dioxo-4,5-dihydro-1H-pyr-
role-2-carboxylates 2a–2d which were reacted further
without isolation. The reactions of pyrrolediones 2a–
2d with 3,4-dihydro-2H-pyran (3), ethyl vinyl ether
(4), and styrene (5) at a ratio of 1:5 on heating in
anhydrous o-xylene at 90–130°C for 10–90 min (until
We previously proposed a convenient procedure for
the synthesis of pyrazolo[5,1-b][1,3]oxazines via
[4+2]-cycloaddition of butyl vinyl ether with 1,4-di-
poles generated in situ from 1-[(diphenylmethylidene)-
OH
HO
O
N
S
OH
O
N
Cl
NO2
N
N
O
O
O
N
N
Me
NO2
F3CO
O
N
O
H
Oxazinomycin
Pretomanid (PA-824)
Thiamethoxam
F3C
Me
Cl
HCl
O
O
N
O
N
N
Me
H
H
Efavirenz
Etifoxine
1531

ZHULANOV et al.
1532
Scheme 1.
R1
N
O
O
O
R1
R1
O
O
Ph
MeO
·
H
(COCl)2
MeO
N
O
O
N
N
Ph
N
O
COOMe
N
Ph
Ph
Ph
Ph
1a–1d
2a–2d
9
O
O
O
O–
R1
MeO
R1
MeO
Ph
Ph
Ph
Ph
N
N
N
N
O
O
10
11
O
O
O
O
R1
MeO
Ph
MeO
O
OH
3
+
N
N
N
N
Ph
H
Ph
O
O
6a–6d
8a
O
O
R2
R2
CH2
R1
4-MeC6H4
MeO
O
OH
4, 5
+
MeO
N
N
N
N
Ph
H
Ph
O
O
7a–7d
8b
1, 2, 6, R1 = Ph (a), C6H4Me-4 (b), C6H4Cl-4 (c), t-Bu (d); 4, R2 = OEt; 5, R2 = Ph; 7, R1 = C6H4Me-4, R2 = OEt (a);
R1 = t-Bu, R2 = OEt (b); R1 = C6H4Me-4, R2 = Ph (c); R1 = C6H4Cl-4, R2 = Ph (d).
disappearance of the dark violet color of azomethine
imines generated by thermolysis) afforded methyl
3-acyl-9,9-diphenyl-4a,7,8,8a-tetrahydro-6H,9H-pyr-
ano[3,2-e]pyrazolo[5,1-b][1,3]oxazine-2-carboxylates
6a–6d and methyl 3-acyl-7,7-diphenyl-6,7-dihydro-
5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylates 7a–7d.
In some cases, methyl 4-acyl-3-hydroxy-1H-pyrazole-
5-carboxylates 8a and 8b were isolated as minor
products. The structure of compounds 6 and 8 was
confirmed by X-ray analysis of 6c and 8b.
Compounds 6a–6d and 7a–7d are colorless crystal-
line solids readily soluble in DMSO, chloroform, and
acetone and insoluble in alkanes and water.
The 1H NMR spectra of 6a–6d contained signals of
aromatic protons and protons in the substituents
thereon, a nine-proton singlet from the tert-butyl group
(in 6d), a three-proton singlet of the ester methoxy
group (δ 3.70–3.93 ppm), signals of protons in the
bridgehead positions (8a-H and 4a-H, δ 3.04–3.10 and
5.77–5.83 ppm, respectively), and methylene proton
signals (6-H, 7-H, 8-H; δ 1.23–4.03 ppm). Compounds
1
7a–7d showed in the H NMR spectra signals from
aromatic substituents, tert-butyl group in 7a (9H), sub-
stituent on C5, methoxycarbonyl group (3H, δ 3.57–
3.80 ppm), 5-H (δ 5.20– 5.27 ppm), and C6H2 group
(2H, δ 3.01–3.80 ppm).
According to the X-ray diffraction data, compound
6c (Fig. 1) crystallized in centrosymmetric space group
belonging to the triclinic crystal system. The pyrazole
ring is planar within 0.005 Å, while the oxazine ring
adopts a half-chair conformation with the C5 and C9
atoms deviating from the O1C3N2C4 plane by 0.638 and
–0.116 Å, respectively. The pyran ring has a chair
conformation. The six-membered heterocycles are cis-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 53 No. 10 2017

THERMOLYSIS OF 1-(METHYLIDENEAMINO)-1H-PYRROLE-2,3-DIONES.
1533
fused, so that the H5 and H9 protons appear in a gauche
C23
C20
C21
C19
C18
orientation with respect to each other. The pyrazole
ring plane forms with the C10C11C12C13C14C15 and
C16C17C18C19C20C21 planes dihedral angles of 63.0 and
76.0°, respectively.
O4
C22
O3
N1
C16
C4
N2
C1
C17
C10
C14
C15
O5
Compounds 8a and 8b are colorless crystalline
solids readily soluble in DMSO, chloroform, and
acetone and insoluble in alkanes and water. Their
1H NMR spectra displayed signals from aromatic
protons and substituents in the aromatic rings, singlets
of the ester group (δ 3.50–3.60 ppm), and broadened
singlets of the NH and OH protons (δ 10.35–10.63 and
13.16–13.20 ppm, respectively).
C24
C2
O1
C3
C13
C5
C12
C30
C11
C25
C9
C6
O2
C29
C26
C27
C8
C7
C28
Cl
According to the X-ray diffraction data, compound
8b (Fig. 2) crystallized in a centrosymmetric space
group belonging to the moniclinic crystal system. The
pyrazole ring is planar within 0.002 Å. Molecules 8b
in crystal are linked to each other through intermolec-
ular hydrogen bonds N2–H2A···O1 [O1···H2A 1.95(2),
N2–H2A 0.89(2), N2 · · · O1 2.779(2) Å] and
O4–H4A ···N1 [O4–H4A 0.88(2), N1 ···H4A 1.86(2),
N1···O4 2.731(2) Å].
Fig. 1. Structure of the molecule of methyl (4aS*,8aR*)-
3-(4-chlorobenzoyl)-9,9-diphenyl-4a,7,8,8a-tetrahydro-
6H,9H-pyrano[3,2-e]pyrazolo[5,1-b][1,3]oxazine-2-carbox-
ylate (6a) according to the X-ray diffraction data. Non-
hydrogen atoms are shown as thermal vibration ellipsoids
with a probability of 50%.
Presumably, the formation of compounds 6a–6d
and 7a–7d involves thermal decarbonylation of pyr-
rolediones 2 with generation of hydrazonoylketenes 9
which undergo intramolecular cyclization to azo-
methine imines 10. The latter are capable of dimeriz-
ing in [3+3] or [4+4] mode provided that no other
trapping reagent is present [6]. Alkenes as dipolaro-
philes react with azomethine imines 10 in the form of
iminium enolates 11 according to the [4+2]-dipolar
cycloaddition path. Compounds 8a and 8b were not
target products; they were formed via addition of water
to azomethine imines 10 with elimination of benzo-
phenone molecule.
purity of the synthesized compounds was checked by
TLC on Silica gel 60 F254 plates (Merck) using ben-
zene–ethyl acetate (5:1) and ethyl acetate as eluent;
spots were visualized by treatment with iodine vapor.
The X-ray diffraction data for compounds 6c and
8b were obtained on an Xcalibur R automated four-
circle diffractometer (Agilent Technologies) according
to standard procedure [MoKα radiation, temperature
295(2) K, ω-scanning with a step of 1°] using
CrysAlisPro software [7]. A correction for absorption
C13
The described reaction is an example of synthesis
of difficultly accessible substituted pyrazolo[5,1-b]-
[1,3]oxazines and pyrano[3,2-e]pyrazolo[5,1-b][1,3]-
oxazines with several functional substituents in the
pyrazole and oxazine rings.
O2
O1
O3
C4
C12
C11
C3
C8
C5
C9
N2
C6
O4
EXPERIMENTAL
C2
C10
C1
C7
The IR spectra were recorded in mineral oil on
N1
1
a Perkin Elmer Spectrum Two spectrometer. The H
and 13C NMR spectra were measured on a Bruker
Avance III HD 400 spectrometer at 400 and 100 MHz,
respectively, using CDCl3 as solvent and hexamethyl-
disiloxane as internal standard. The elemental analyses
were obtained on a Vario Micro cube analyzer. The
Fig. 2. Structure of the molecule of methyl 3-hydroxy-4-(4-
methylbenzoyl)-1H-pyrazole-5-carboxylate (8b) according
to the X-ray diffraction data. Non-hydrogen atoms are shown
as thermal vibration ellipsoids with a probability of 50%.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 53 No. 10 2017

ZHULANOV et al.
1534
was applied empirically using SCALE3 ABSPACK
algorithm [7]. The structures were solved by the direct
method using SHELXS-97 and were refined against F2
in anisotropic approximation for non-hydrogen atoms
using SHELXL-97 [8]; hydrogen atoms were included
in the refinement process according to the riding model
in isotropic approximation with dependent thermal
parameters.
spectrum, δ, ppm: 1.31 d.d (1H, J = 12.3, 4.0 Hz),
1.57–1.73 m (1H), 1.73–1.85 m (2H, CH2), 3.10 d.d.d
(1H, OCHCH, J = 12.0, 3.9, 2.1 Hz), 3.71 s (3H,
MeO), 3.79 d (1H, OCH2, J = 11.3 Hz), 3.86–4.00 m
(1H, OCH2), 5.83 s (1H, OCH), 7.05–7.16 m (2H,
H
H
arom), 7.29–7.70 m (11H, Harom), 7.86–7.96 m (2H,
arom). 13C NMR spectrum, δC, ppm: 20.9, 24.7, 41.5,
52.2 (MeO), 61.5, 71.8, 97.1, 104.0, 127.2 (2C), 127.9
(2C), 128.0, 128.3 (2C), 128.6, 128.8 (2C), 129.1 (2C),
129.3 (2C), 132.7, 138.8, 138.9, 141.4, 142.8, 151.8,
162.6 (MeOCO), 188.1 (ArCO). Found, %: C 72.77;
H 5.27; N 5.63. C30H26N2O5. Calculated, %: C 72.86;
H 5.30; N 5.66.
The data for compound 6c were acquired from
a 0.5×0.3×0.2-mm fragment of a colorless single
crystal. Triclinic crystal system, space group P–1; unit
cell parameters: a = 7.3713(10), b = 10.3134 (12), c =
18.546(2) Å; α = 99.188(9), β = 99.071(10), γ =
110.235(12)°; Z = 2. Completeness 99.9% for
θ < 26.00°. Final divergence factors: R1 = 0.0557,
wR2 = 0.1294 [for 4226 reflections with I > 2σ(I)];
R1 = 0.0807, wR2 = 0.1468 (for all 5899 independent
reflections, Rint = 0.0415); goodness of fit 1.045; Δρ =
0.235/–0.385 ēÅ–3.
The mother liquor was concentrated, and the resi-
due was dried. Yield of 8a 12%, mp 205–206°C (from
toluene). IR spectrum, ν, cm–1: 3250, 1750, 1720,
1
1670. H NMR spectrum, δ, ppm: 3.50 s (3H, MeO),
7.49 t (2H, Harom, J = 7.6 Hz), 7.61 t (1H, Harom, J =
7.2 Hz), 7.61 d (2H, Harom, J = 5.8 Hz), 10.63 s
(1H, NH), 13.16 s (1H, OH). Found, %: C 58.36;
H 4.05; N 11.35. C12H10N2O4. Calculated, %: C 58.54;
H 4.09; N 11.38.
The data for compound 8b were acquired from
a 0.4×0.3×0.25-mm fragment of a colorless single
crystal. Monoclinic crystal system, space group P21/n;
unit cell parameters: a = 10.979(2), b = 10.5429(19),
c = 11.632(3) Å; β = 111.30(3)°; Z = 4. Completeness
99.8% for θ < 26.00°. Final divergence factors: R1 =
0.0498, wR2 = 0.1260 [for 2327 reflections with I >
2σ(I)]; R1 = 0.0640, wR2 = 0.1379 (for all 2936 in-
dependent reflections, Rint = 0.0386); goodness of fit
1.067; Δρ = 0.204/–0.356 ēÅ–3.
Compounds 6b–6d were synthesized in a similar
way.
Methyl (4aS*,8aR*)-3-(4-methylbenzoyl)-9,9-di-
phenyl-4a,7,8,8a-tetrahydro-6H,9H-pyrano[3,2-e]-
pyrazolo[5,1-b][1,3]oxazine-2-carboxylate (6b).
Yield 26%, mp 246–248°C (from acetone). IR spec-
trum, ν, cm–1: 1724, 1650, 1606, 1566. 1H NMR spec-
trum, δ, ppm: 1.23–1.37 m (1H), 1.59–1.80 m (3H,
CH2), 2.47 s (3H, Me), 3.10 d (1H, OCHCH, J =
10.4 Hz), 3.74 s (3H, MeO), 3.80 d (1H, J = 9.4 Hz),
3.89–4.03 m (1H, OCH2), 5.81 s (1H, OCH), 7.15–
7.07 m (2H, Harom), 7.25–7.54 m (8H, Harom), 7.66 d
(2H, Harom, J = 7.6 Hz), 7.82 d (2H, Harom, J = 8.1 Hz).
13C NMR spectrum, δC, ppm: 20.9, 21.8, 24.8, 41.5,
52.2 (MeO), 61.6, 71.9, 97.0, 104.2, 127.2 (2C), 127.9
(2C), 128.0, 128.6, 128.9 (2C), 129.0 (2C), 129.1 (2C),
129.6 (2C), 136.3, 138.9, 141.4, 142.7, 143.6, 151.5,
162.6 (MeOCO), 187.8 (ArCO). Found, %: C 73.17;
H 5.53; N 5.48. C31H28N2O5. Calculated, %: C 73.21;
H 5.55; N 5.51.
The CIF files containing complete crystallographic
data sets were deposited to the Cambridge Crystallo-
graphic Data Centre [CCDC entry nos. 1 544 136
(6c) and 1 544 137 (8b)] and are available at
www.ccdc.cam.ac.uk.
Methyl (4aS*,8aR*)-3-benzoyl-9,9-diphenyl-
4a,7,8,8a-tetrahydro-6H,9H-pyrano[3,2-e]pyrazolo-
[5,1-b][1,3]oxazine-2-carboxylate (6a) and methyl
4-benzoyl-3-hydroxy-1H-pyrazole-5-carboxylate
(8a). Oxalyl chloride, 1.0 mmol, was added to a solu-
tion of 1.0 mmol of compound 1a in 5 mL of
anhydrous chloroform. The mixture was refluxed for
90 min with stirring, 5 mL of anhydrous o-xylene was
added, and chloroform was distilled off by raising the
temperature to 130°C. The mixture was refluxed for
10 min at 130–140°C, 5.0 mmol of 3,4-dihydro-2H-
pyran was added, and the mixture was refluxed for
90 min more. It was then cooled and evaporated under
reduced pressure, and the residue was recrystallized.
Yield of 6a 23%, mp 175–177°C (from acetone). IR
Methyl (4aS*,8aR*)-3-(4-chlorobenzoyl)-9,9-di-
phenyl-4a,7,8,8a-tetrahydro-6H,9H-pyrano[3,2-e]-
pyrazolo[5,1-b][1,3]oxazine-2-carboxylate (6c).
Yield 25%, mp 261–263°C (from acetone). IR spec-
trum, ν, cm–1: 1722, 1656, 1586, 1565. 1H NMR spec-
trum, δ, ppm: 1.23 d.d (1H, J = 8.8, 5.2 Hz), 1.50–
1.66 m (1H, CH2), 1.67–1.80 m (2H, CH2), 3.04 d.d.d
(1H, OCHCH, J = 12.3, 4.0, 2.1 Hz), 3.70 s (3H,
1
spectrum, ν, cm–1: 1724, 1655, 1640, 1566. H NMR
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 53 No. 10 2017

THERMOLYSIS OF 1-(METHYLIDENEAMINO)-1H-PYRROLE-2,3-DIONES.
1535
MeO), 3.72–3.79 m (1H, OCH2), 3.80–3.92 m (1H,
OCH2), 5.77 s (1H, OCH), 6.95–7.12 m (2H, Harom),
7.23–7.32 m (3H, Harom), 7.33–7.49 m (5H, Harom),
7.56–7.63 m (2H, Harom), 7.71–7.89 m (2H, Harom).
13C NMR spectrum, δC, ppm: 20.9, 24.7, 41.4, 52.3
(MeO), 61.6, 71.9, 97.3, 103.7, 127.2 (2C), 127.9 (2C),
128.0, 128.7 (3C), 128.8 (2C), 129.2 (2C), 130.8 (2C),
137.2, 138.8, 139.2, 141.3, 142.7, 151.8, 162.5
(MeOCO), 186.8 (ArCO). Found, %: C 68.07; H 4.73;
N 5.26. C30H25ClN2O5. Calculated, %: C 68.12;
H 4.76; N 5.30.
14.9, 21.8, 42.1, 52.1 (MeO), 65.7, 68.3, 99.6, 104.3,
127.2 (2C), 128.3 (2C), 128.4 (2C), 128.6 (2C), 128.9
(2C), 129.0 (2C), 129.5 (2C), 136.6, 141.0, 142.0,
142.9, 143.2, 151.6, 162.6 (MeOCO), 188.2 (ArCO).
Found, %: C 72.49; H 5.65; N 5.61. C30H28N2O5.
Calculated, %: C 72.56; H 5.68; N 5.64.
The mother liquor obtained after recrystallization of
7a from acetone was concentrated, and the residue was
recrystallized from toluene. Yield of 8b 15%, mp 210–
212°C (from toluene). IR spectrum, ν, cm–1: 3250,
1
1770, 1670, 1620. H NMR spectrum, δ, ppm: 2.40 s
(3H, Me), 3.60 s (3H, MeO), 7.26 d (2H, Harom, J =
8.0 Hz), 7.60 d (2H, Harom, J = 8.0 Hz), 10.35 s (1H,
NH), 13.20 s (1H, OH). Found, %: C 59.82; H 4.51;
N 10.73. C13H12N2O4. Calculated, %: C 60.00; H 4.65;
N 10.76.
Methyl (4aS*,8aR*)-3-(2,2-dimethylpropanoyl)-
9,9-diphenyl-4a,7,8,8a-tetrahydro-6H,9H-pyrano-
[3,2-e]pyrazolo[5,1-b][1,3]oxazine-2-carboxylate
(6d). Yield 26%, mp 191–92°C (from acetone). IR
1
spectrum, ν, cm–1: 1728, 1697, 1662, 1545. H NMR
spectrum, δ, ppm: 1.35 s (9H, Me3C), 1.56–1.69 m
(2H), 1.74–1.85 m (2H), 3.08 d.d.d (1H, OCHCH, J =
12.4, 3.9, 2.1 Hz), 3.84–3.91 m (1H), 3.93 s (3H,
MeO), 3.95–4.03 m (1H), 5.81 s (1H, OCH), 7.05–
7.12 m (2H, Harom), 7.29–7.39 m (4H, Harom), 7.40–
7.47 m (4H, Harom). 13C NMR spectrum, δC, ppm: 20.8,
24.8, 26.6 (3C), 41.7, 44.8, 52.3 (MeO), 61.7, 71.8,
97.0, 104.8, 127.1 (2C), 127.9 (2C), 128.0, 128.1,
128.2, 128.3, 128.5, 128.9 (2C), 129.1 (2C), 129.6,
163.0 (MeOCO), 204.0 (Me3CCO). Found, %:
C 70.73; H 6.60; N 5.85. C28H30N2O5. Calculated, %:
C 70.87; H 6.73; N 5.90.
Compounds 7b–7d were synthesized in a similar
way.
Methyl 3-(2,2-dimethylpropanoyl)-5-ethoxy-
7,7-diphenyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]-
oxazine-2-carboxylate (7b). Yield 32%, mp 133–
135°C (from acetone). IR spectrum, ν, cm–1: 1737,
1
1697, 1656, 1539. H NMR spectrum, δ, ppm: 1.18 t
(3H, CH3CH2, J = 7.1 Hz), 1.28 s (9H, Me3C), 3.01–
3.07 m (2H, CHCH2), 3.44–3.62 m (1H, CH2O),
3.80 s (3H, MeO), 3.82–3.96 m (1H, CH2O), 5.20 d.d
(1H, CHCH2, J = 10.6, 2.6 Hz), 7.04–7.11 m (2H,
H
arom), 7.15–7.45 m (8H, Harom). 13C NMR spectrum,
δC, ppm: 15.0, 26.6 (3C, Me3C), 42.3, 44.8, 52.2
(MeO), 65.8, 68.3, 99.8, 105.0, 127.1 (2C), 128.3 (2C),
128.6 (2C), 129.0 (2C), 129.3 (2C), 134.1, 141.1,
142.0, 147.9, 162.9 (MeOCO), 204.4 (Me3CCO).
Found, %: C 70.02; H 6.51; N 6.01. C27H30N2O5. Cal-
culated, %: C 70.11; H 6.54; N 6.06.
Methyl 5-ethoxy-3-(4-methylbenzoyl)-7,7-di-
phenyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-
2-carboxylate (7a) and methyl 3-hydroxy-4-
(4-methylbenzoyl)-1H-pyrazole-5-carboxylate (8b).
Oxalyl chloride, 1.0 mmol, was added to a solution of
1.0 mmol of compound 1b in 5 mL of anhydrous
chloroform. The mixture was refluxed for 10 min with
stirring, 5 mL of anhydrous o-xylene was added, and
chloroform was distilled off by raising the temperature
to 130. The mixture was refluxed for 10 min at 130–
140°C and cooled to 90–100°C, 5.0 mmol of ethyl
vinyl ether was added, and the mixture was heated for
15 min more. The resulting solution was cooled and
evaporated under reduced pressure. Yield of 7a 26%,
mp 180–183°C (from acetone). IR spectrum, ν, cm–1:
Methyl 3-(4-methylbenzoyl)-5,7,7-triphenyl-6,7-
dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carbox-
ylate (7c). The mixture was refluxed for 10 min at
130–140°C, 5.0 mmol of styrene was added, and the
mixture was heated for 60 min more. The solution was
cooled and evaporated under reduced pressure. Yield
21%, mp 214–216°C (from acetone). IR spectrum, ν,
1
cm–1: 1731, 1640, 1605, 1550. H NMR spectrum, δ,
ppm: 2.46 s (3H, Me), 3.12 d.d (1H, CHCH2, J = 14.8,
10.7 Hz), 3.18 d.d (1H, CHCH2, J = 14.8, 2.7 Hz),
3.64 s (3H, MeO), 5.27 d.d (1H, CHCH2, J = 10.6,
2.6 Hz), 7.26–7.56 m (19H, Harom). 13C NMR spec-
trum, δC, ppm: 21.8 (Me), 45.0, 52.0 (MeO), 69.2,
76.4, 104.2, 125.7 (2C), 127.2 (2C), 128.4 (2C), 128.5
(2C), 128.7 (2C), 128.8 (2C), 128.9, 129.0 (2C), 129.2
(2C), 129.5 (2C), 136.6, 137.7, 141.4, 141.9, 142.7,
1
1740, 1634, 1607, 1550. H NMR spectrum, δ, ppm:
1.06 t (3H, J = 6.8 Hz), 2.39 s (3H, Me), 3.00–3.13 m
(2H, CHCH2), 3.39–3.51 m (1H, OCH2), 3.57 s (3H,
MeO), 3.67–3.80 m (1H, OCH2), 5.21 d (1H, CHCH2,
J = 6.8 Hz), 7.13 d (2H, Harom, J = 6.5 Hz), 7.18–
7.28 m (4H, Harom), 7.28–7.44 m (6H, Harom), 7.74 d
(2H, Harom, J = 7.5 Hz). 13C NMR spectrum, δC, ppm:
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 53 No. 10 2017

ZHULANOV et al.
1536
REFERENCES
143.3, 152.7, 162.6 (MeOCO), 188.2 (ArCO). Found,
%: C 77.09; H 5.21; N 5.26. C34H28N2O4. Calculated,
%: C 77.25; H 5.34; N 5.30.
1. Haneishi, T., Okazaki, T., Hata, T., Tamura, C.,
Nomura, M., Naito, A., Seki, I., and Arai, M., J. Antibiot.,
1971, vol. 24, p. 797.
2. Singh, R., Manjunatha, U., Boshoff, H.I.M., Ha, Y.H.,
Niyomrattanakit, P., Ledwidge, R., Dowd, C.S., Lee, I.Y.,
Kim, P., Zhang, L., Kang, S., Keller, T.H., Jiricek, J., and
Barry, C.E., Science, 2008, vol. 322, p. 1392.
Methyl 3-(4-chlorobenzoyl)-5,7,7-triphenyl-6,7-
dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carbox-
ylate (7d). Yield 40%, mp 198–200°C (from acetone).
IR spectrum, ν, cm–1: 1737, 1636, 1587, 1546.
1H NMR spectrum, δ, ppm: 3.09 d.d (1H, CHCH2, J =
14.8, 10.8 Hz), 3.16 d.d (1H, CHCH2, J = 14.8,
2.6 Hz), 3.61 s (3H, MeO), 5.21 d.d (1H, CHCH2, J =
10.8, 2.4 Hz), 7.18–7.50 m (17H, Harom), 7.77–7.84 m
(2H, Harom). 13C NMR spectrum, δC, ppm: 44.8, 52.2
(MeO), 69,3, 76.7, 103.8, 125.7 (2C), 127.2 (2C),
128.5 (2C), 128.6 (2C), 128.7 (4C), 128.9 (2C), 129.0,
129.2 (2C), 130.7 (2C), 137.4, 137.5, 138.9, 141.3,
141.8, 142.7, 153.0, 162.5 (MeOCO), 187.1 (ArCO).
Found, %: C 72.11; H 4.46; N 5.06. C33H25ClN2O4.
Calculated, %: C 72.19; H 4.59; N 5.10.
3. Tomizawa, M. and Casida, J.E., Annu. Rev. Entomol.,
2003, vol. 48, p. 339.
4. Kuch, H., Schmitt, K., Seidl, G., and Hoffmann, I.,
US Patent no. 3725404A, 1973.
5. Young, D.S., Britcher, F.S., Tran, O.L., Payne, S.L.,
Lumma, C.W., Lyle, A.T., Huff, R.J., Sanderson, P.,
Olsen, B.D., Carroll, S.S., Pettibone, J.D., O’Brien, A.J.,
Ball, G.R., Balani, K.S., Lin, H.J., Chen, W.I.,
Schleif, A.W., Sardana, V.V., Long, J.W., Byrnes, W.V.,
and Emini, A.E., Antimicrob. Agents Chemother., 1995,
vol. 39, p. 2602.
This study was performed under financial support
by the Ministry of Education and Science of the
Russian Federation, by the Council for Grants at the
President of the Russian Federation (project no. MK-
1657.2017.3), and by the Russian Foundation for Basic
Research (project no. 16-43-590613).
6. Zhulanov, V.E., Dmitriev, M.V., Maslivets, A.N., and
Rubin, M., RSC Adv., 2016, vol. 6, p. 90239.
7. CrysAlisPro, Version 1.171.36.28 (release 01-02-2013
CrysAlis171 .NET), Agilent Technologies.
8. Sheldrick, G.M., Acta Crystallogr., Sect. A, 2008, vol. 64,
p. 112.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 53 No. 10 2017