Five-membered 2,3-dioxo heterocycles: XCVIII.* [4 + 2]-cycloaddition of alkyl vinyl ethers to 3-aroyl-1H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4- triones. A new synthetic approach to heteroanalogs of 13(14→8)-abeo steroids

Article abstract of DOI:10.1134/S1070428013120105

3-Aroyl-1H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones reacted with alkyl vinyl ethers according to the [4 + 2]-cycloaddition pattern with formation of substituted (1S*,16R*)- and (1R*,16R*)-16-alkoxy-14- aryl-3,15-dioxa-10-azatetracyclo[8.7.0.01,13.04,9

Full text of DOI:10.1134/S1070428013120105

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 12, pp. 1762–1767. © Pleiades Publishing, Ltd., 2013.
Original Russian Text © E.E. Stepanova, Z.G. Aliev, A.N. Maslivets, 2013, published in Zhurnal Organicheskoi Khimii, 2013, Vol. 49, No. 12, pp. 1781–1786.
Five-Membered 2,3-Dioxo Heterocycles:
XCVIII.* [4+2]-Cycloaddition of Alkyl Vinyl Ethers
to 3-Aroyl-1H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones.
A New Synthetic Approach to Heteroanalogs
of 13(14→8)-Abeo Steroids
E. E. Stepanovaa, Z. G. Alievb, and A. N. Maslivetsa
a Perm State National Research University, ul. Bukireva 15, Perm, 614990 Russia
e-mail: koh2@psu.ru
b Institute of Chemical Physics Problems, Russian Academy of Sciences,
Chernogolovka, Moscow oblast, Russia
Received December 5, 2012
Abstract—3-Aroyl-1H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones reacted with alkyl vinyl ethers according
to the [4+2]-cycloaddition pattern with formation of substituted (1S*,16R*)- and (1R*,16R*)-16-alkoxy-14-
aryl-3,15-dioxa-10-azatetracyclo[8.7.0.01,13.04,9]heptadeca-4,6,8,13-tetraene-2,11,12-triones. The structure of
(1S*,16R*)-7-chloro-16-ethoxy-14-phenyl-3,15-dioxa-10-azatetracyclo[8.7.0.01,13.04,9]heptadeca-4,6,8,13-tetra-
ene-2,11,12-trione was determined by X-ray analysis. A new synthetic approach was developed to hetero-
analogs of 13(14→8)-abeo steroids, substituted 3,15-dioxa-10-azatetracyclo[8.7.0.01,13.04,9]heptadecanes.
DOI: 10.1134/S1070428013120105
Cycloaddition to the conjugated bond system of
4-acyl-1H-pyrrole-2,3-diones fused to an isoquinoline
fragment has been extensively studied while develop-
ing a strategy for building up heterocyclic system of
Erythrina alkaloids [2–4]. Thermal [4+2]-cycload-
dition of polar C=C dienophiles to the C5=C4–C=O
conjugated bond system of monocyclic 4-aroyl-sub-
stituted 1H-pyrrole-2,3-diones led to the formation of
pyrano[4,3-b]pyrrole heterocyclic system [4–6]. Cy-
cloaddition of olefins to 4-acyl-substituted 1H-pyrrole-
2,3-diones fused to a 1,4-benzoxazin-2-one fragment
(pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones) was not
studied previously.
Compound III was synthesized in turn by reaction of
3-(3-bromobenzoyl)pyruvic acid (IV) with 4-chloro-2-
aminophenol (V); on the basis of spectral data it was
assigned Z configuration which is typical of such com-
pounds [10].
Pyrrolobenzoxazinetriones Ia–Ig were brought into
reactions with alkyl vinyl ethers IIa and IIb at a molar
ratio of 1:5 in boiling benzene; the mixture was heated
for 15–60 min until disappearance of violet color
typical of initial compounds Ia–Ig. As a result, we
obtained representatives of a new class of difficultly
accessible fused aza heterocycles, diastereoisomeric
(1S*,16R*)- and (1R*,16R*)-16-alkoxy-14-aryl-3,15-
dioxa-10-azatetracyclo[8.7.0.01,13.04,9]heptadeca-
4,6,8,13-tetraene-2,11,12-triones VIa–VIi** and
VIIa–VIIi. Isomers VIa–VIi were formed as the major
products, while compounds VIIa–VIIi were minor
ones; as a rule, the latter were not isolated and were
identified in the 1H NMR spectra of the corresponding
major isomers. By fractional crystallization we suc-
ceeded in separating isomers VIa–VIc and VIIa–VIIc.
In the present work we examined the reaction of
3-aroyl-1H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-tri-
ones Ia–Ig with alkyl vinyl ethers IIa and IIb.
Pyrrolobenzoxazinetriones Ia–If [7–9] were synthe-
sized according to known methods, whereas previously
unknown compound Ig was prepared by treatment of
(Z)-3-[2-(3-bromophenyl)-2-oxoethylidene]-3,4-di-
hydro-1,4-benzoxazin-2-one (III) with oxalyl chloride.
* For communication XCVII, see [1].
** For preliminary communication, see [9, 11].
1762

FIVE-MEMBERED 2,3-DIOXO HETEROCYCLES: XCVIII.
1763
Scheme 1.
O
O
O
N
O
O
O
O
O
R
NH2
OH
(COCl)2
OH
R
N
H
R
+
Ar
Ar
O
O
Ar
O
IV
V
III
Ia–Ig
AlkO
O
AlkO
O
O
O
H
H
3
16
4
9
2
O15
O
AlkOCH=CH2 (IIa, IIb)
10
N
17
13
+
1
R
R
N
14
12
Ar
Ar
11
O
O
O
O
VIa–VIi
VIIa–VIIi
I, Ar = Ph (a, f), 4-EtOC6H4 (b), 4-MeOC6H4 (c), 4-BrC6H4 (d), 4-O2NC6H4 (e), 3-BrC6H4 (g); R = H (a–e), Cl (f, g); II, Alk = Et (a),
Bu (b); III, Ar = 3-BrC6H4, R = Cl; IV, Ar = 3-BrC6H4; V, R = Cl; VI, VII, Alk = Et (a, c, e–h), Bu (b, d, i); Ar = Ph (a–c),
4-EtOC6H4 (d, g), 4-MeOC6H4 (f), 4-O2NC6H4 (e), 4-BrC6H4 (h), 3-BrC6H4 (i); R = H (a, b, d–h), Cl (c, i).
tion of the 16-alkoxy group. This conclusion is sup-
ported by comparison of the chemical shifts of 16-H,
which are larger for diastereoisomers VIa–VIi than for
VIIa–VIIi, in keeping with the known relation for
cyclohexanes (δeq > δax). According to the signal
Compounds VIa–VIi and VIIa–VIIc were yellow
crystalline substances which melted with decomposi-
tion at high temperature. They are readily soluble in
DMSO and DMF, poorly soluble in other organic
solvents, and insoluble in alkanes and water. The
solubility of compounds VIa–VIi in common organic
solvents and their Rf values are appreciably lower as
compared to the corresponding stereoisomers VIIa–
VIIi. The IR spectra of VI and VII contained absorp-
tion bands due to stretching vibrations of the lactone
carbonyl group (C2=O, 1764–1802 cm–1), lactam car-
bonyl group C11=O, and ketone carbonyl group C12=O
(1715–1731 cm–1).
1
intensity ratio in the H NMR spectra of the reaction
mixtures, the ratio of isomers VI and VII was ~5:1.
The structure of compound VIc was determined by
X-ray analysis (see figure). Neither shortened intermo-
lecular contacts nor hydrogen bonds were found in the
crystalline structure of VIc. All bond lengths and bond
angles do not differ appreciably from the correspond-
ing standard values. The oxazine and pyran rings in
molecule VIc adopt an envelope conformation and are
1
Compounds VIa–VIi displayed in the H NMR
spectra signals from protons in aliphatic substituents,
aromatic rings and substituents therein, a multiplet
from the 16-H proton at δ 5.73–5.84 ppm, and multi-
plets from two nonequivalent methylene protons on
C17 at δ 2.34–2.41 and 2.39–2.45 ppm with the
C16
C15
C11
C10
O5
C4
O1
O2
C12
3
3
C1
coupling constants Jax,eq = 3.2–4.2 and Jeq,eq = 0.0–
2.4 Hz, respectively. The 16-H and 17-H protons form
an ABX three-spin system, and analysis of the vicinal
coupling constants for 17-H indicates that the 16-H
proton occupies equatorial position and that the alkoxy
C3
Cl
C9
C2
O6
C17
C13
C5
C22
C14
C6
C7
N
1
C18
group is axial. In addition, the H NMR spectra of
C19
VIa–VIi contained minor signals belonging to isomers
VIIa–VIIi, in particular at δ 5.56–5.64 (m, 16-H),
C8
C21
O4
3
O3
C20
2.13–2.26 (m, 17-H, Jax,ax = 9.9–10.5 Hz), and 2.61–
2.79 ppm (m, 17-H, 3Jax,eq = 3.9–4.4 Hz). As in isomers
VI, these protons constitute an ABX spin system, and
the vicinal coupling constants for 17-H correspond to
axial orientation of 16-H and hence equatorial orienta-
Structure of the molecule of (1S*,16R*)-7-chloro-16-ethoxy-
14-phenyl-3,15-dioxa-10-azatetracyclo[8.7.0.01,13.04,9]hepta-
deca-4,6,8,13-tetraene-2,11,12-trione (VIc) according to the
X-ray diffraction data.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 12 2013

STEPANOVA et al.
1764
bent along the N · · · C1 and C3 · · · C6 axes through
dihedral angles of 43.4 and 45.9°, respectively.
C 50.03; H 1.59; N 3.34. C18H7BrClNO5. Calculated,
%: C 49.97; H 1.63; N 3.24.
Obviously, compounds VIa–VIi and VIIa–VIIi are
formed via thermally initiated [4+2]-cycloaddition of
3-aroyl-1H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-tri-
ones Ia–Ig (O=C–C3=C3a conjugated diene system) to
the polarized C=C bond of alkyl vinyl ether IIa and
IIb. The higher yield of isomers VI as compared to
VII indicates that pseudoaxial orientation of the
alkoxy group in the transition state is more favorable.
(1S*,16R*)-16-Ethoxy-14-phenyl-3,15-dioxa-10-
azatetracyclo[8.7.0.01,13.04,9]heptadeca-4,6,8,13-
tetraene-2,11,12-trione (VIa) and (1R*,16R*)-16-
ethoxy-14-phenyl-3,15-dioxa-10-azatetracyclo-
[8.7.0.01,13.04,9]heptadeca-4,6,8,13-tetraene-2,11,12-
trione (VIIa). A solution of 45.0 mmol of ethyl vinyl
ether in 10 mL of anhydrous benzene was added to
a solution of 9.0 mmol of compound Ia in 70 mL of
anhydrous benzene, and the mixture was heated for
40 min under reflux (until violet color disappeared).
The mixture was cooled, and the yellow precipitate
(compound VIa was filtered off. Yield 59%, mp 248–
250°C (decomp., from toluene). IR spectrum, ν, cm–1:
Compounds VI and VII may be regarded as hetero-
cyclic analogs of 13(14→8)-abeo-steroids, danka-
sterone [12] and abeohyousterone [13], which possess
a rarely occurring fused carbocyclic skeleton and
exhibit pronounced antitumor activity. Thus the de-
scribed reaction provides a new synthetic approach to
such compounds.
1
1786 (C2=O), 1724 (C11=O, C12=O). H NMR spec-
trum, δ, ppm: 1.11 t (3H, CH3, J = 7.0 Hz), 2.36 d.d
(1H, 17-H, J = 3.6, 13.6 Hz), 2.42 d.d (1H, 17-H, J =
2.0, 14.0 Hz), 3.72 m and 3.82 m (2H, OCH2), 5.79 d.d
(1H, CH, J = 2.0, 3.6 Hz), 7.34–7.95 m (9H, Harom).
13C NMR spectrum, δC, ppm: 14.67 (Me), 38.88 (C17),
54.48 (OCH2), 65.65 (C1), 100.33 (C16), 102.86 (C13),
116.68–143.10 (Carom), 159.17 (C11), 160.77 (C2),
166.92 (C14), 175.96 (C12). Found, %: C 67.50; H 4.42;
N 3.53. C22H17NO6. Calculated, %: C 67.51; H 4.38;
N 3.58.
EXPERIMENTAL
The IR spectra were recorded on an FSM-1201
spectrophotometer from samples dispersed in mineral
1
oil. The H and 13C NMR spectra were obtained on
a Bruker AM-400 instrument at 400 and 100 MHz,
respectively, using DMSO-d6 as solvent and tetra-
methylsilane as internal reference. The purity of the
isolated compounds was checked by TLC on Silufol
plates using benzene–ethyl acetate (5:1) and benzene
as eluents.
The filtrate was evaporated to 1/10 of the initial
volume and cooled, and the yellow precipitate of
isomer VIIa was filtered off. Yield 27%, mp 243–
245°C (decomp., from benzene). IR spectrum, ν, cm–1:
(Z)-3-[2-(3-Bromophenyl)-2-oxoethylidene]-6-
chloro-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one
(III). A mixture of 1.0 mmol of 3-bromobenzoyl-
pyruvic acid and 1.0 mmol of 2-amino-4-chlorophenol
in 50 mL of propan-2-ol was heated for 90 min under
reflux. The mixture was cooled, and the orange solid
was filtered off. Yield 81%, mp 210–212°C (from
toluene). IR spectrum, ν, cm–1: 3073 br (NH), 1759
1
1774 (C2=O), 1728 (C11=O, C12=O). H NMR spec-
trum, δ, ppm: 1.21 t (3H, CH3, J = 7.2 Hz), 2.19 d.d
(1H, 17-H, J = 10.4, 12.8 Hz), 2.62 d.d (1H, 17-H, J =
4.2, 13.0 Hz), 3.82 m and 4.04 m (2H, OCH2), 5.60 d.d
(1H, CH, J = 4.0, 10.4 Hz), 7.34–7.85 m (9H, Harom).
Found, %: C 67.46; H 4.35; N 3.57. C22H17NO6. Cal-
culated, %: C 67.51; H 4.38; N 3.58.
1
(C2=O), 1626 (C2′=O). H NMR spectrum, δ, ppm:
Compounds VIb, VIc, VIIb, and VIIc were syn-
6.89 s (1H, CH), 7.16–8.11 m (7H, Harom), 12.59 s
(1H, NH). Found, %: C 50.79; H 2.48; N 3.65.
C16H9BrClNO3. Calculated, %: C 50.76; H 2.40; N 3.70.
thesized in a similar way.
(1S*,16R*)-16-Butoxy-14-phenyl-3,15-dioxa-10-
azatetracyclo[8.7.0.01,13.04,9]heptadeca-4,6,8,13-
tetraene-2,11,12-trione (VIb). Yield 61%, mp 212–
213°C (decomp., from benzene). IR spectrum, ν, cm–1:
3-(3-Bromobenzoyl)-8-chloro-1H-pyrrolo[2,1-c]-
[1,4]benzoxazine-1,2,4-trione (Ig). A mixture of
1.0 mmol of compound III and 1.1 mmol of oxalyl
chloride in 50 mL of anhydrous benzene was heated
for 110 min under reflux. The mixture was cooled, and
the violet precipitate was filtered off. Yield 87%,
mp 204–206°C (decomp.). IR spectrum, ν, cm–1: 1786
1788 (C2=O), 1725 (C11=O, C12=O). H NMR spec-
1
trum, δ, ppm: 0.83 t (3H, CH3, J = 7.3 Hz), 1.29 m
(2H, CH2Me), 1.46 m (2H, CH2Et), 2.37 d.d (1H,
17-H, J = 4.2, 13.6 Hz), 2.42 d.d (1H, 17-H, J = 1.2,
14.0 Hz), 3.67 m and 3.78 m (2H, OCH2), 5.77 d.d
(1H, CH, J = 1.4, 4.2 Hz), 7.33–7.93 m (9H, Harom).
13C NMR spectrum, δC, ppm: 13.57 (Me), 18.37
1
(C4=O), 1740 (C1=O, C2=O), 1655 (C1′=O). H NMR
spectrum, δ, ppm: 7.37–8.32 m (7H, Harom). Found, %:
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 12 2013

FIVE-MEMBERED 2,3-DIOXO HETEROCYCLES: XCVIII.
1765
(CH2Me), 30.92 (CH2CH2Me), 38.88 (C17), 54.46
(OCH2), 69.05 (C1), 100.67 (C16), 102.81 (C13), 116.68–
143.13 (Carom), 159.17 (C11), 160.72 (C2), 166.54 (C14),
175.91 (C12). Found, %: C 68.78; H 5.07; N 3.28.
C24H21NO6. Calculated, %: C 68.73; H 5.05; N 3.34.
scanning (monochromatized MoKα irradiation; 2Θ ≤
50°) from a 0.4×0.3×0.2-mm single crystal. Total of
4342 reflections were measured, 3401 of which were
independent (Rint = 0.0246). No correction for absorp-
tion was applied (μ = 0.239 mm–1). The structure was
solved by the direct method using SIR92 program [14]
and subsequent calculation of electron density maps.
The positions of hydrogen atoms were set geometrical-
ly. The positions of non-hydrogen atoms were refined
by the full-matrix least-square procedure in anisotropic
approximation using SHELXL-97 software package
[15]. The final divergence factors were R1 = 0.0447,
wR2 = 0.0963 for 2250 reflections with I ≥ 2σ(I) and
R1 = 0.0803, wR2 = 0.1100 for all independent reflec-
tions; 271 variables; Δρmax = 0.157; goodness of fit
1.013. The CIF file containing complete information
on the structure of compound VIc was deposited
to the Cambridge Crystallographic Data Centre
(entry no. CCDC 884 511) and is available at
www.ccdc.cam.ac.uk/data_request/cif.
(1R*,16R*)-16-Butoxy-14-phenyl-3,15-dioxa-10-
azatetracyclo[8.7.0.01,13.04,9]heptadeca-4,6,8,13-
tetraene-2,11,12-trione (VIIb). Yield 24%, mp 198–
200°C (decomp., from benzene). IR spectrum, ν, cm–1:
1
1764 (C2=O), 1729 (C11=O, C12=O). H NMR spec-
trum, δ, ppm: 0.89 t (3H, CH3, J = 7.2 Hz), 1.37 m
(2H, CH2Me), 1.57 m (2H, CH2Et), 2.18 d.d (1H,
17-H, J = 9.4, 12.6 Hz), 2.62 d.d (1H, 17-H, J = 4.4,
12.8 Hz), 3.80 m and 4.01 m (2H, OCH2), 5.60 d.d
(1H, CH, J = 4.0, 10.4 Hz), 7.33–7.85 m (9H, Harom).
Found, %: C 68.72; H 5.08; N 3.33. C24H21NO6. Cal-
culated, %: C 68.73; H 5.05; N 3.34.
(1S*,16R*)-7-Chloro-16-ethoxy-14-phenyl-3,15-
dioxa-10-azatetracyclo[8.7.0.01,13.04,9]heptadeca-
4,6,8,13-tetraene-2,11,12-trione (VIc). Yield 67%,
mp 243–245°C (decomp., from toluene). IR spectrum,
(1S*,16R*)-16-Butoxy-14-(4-ethoxyphenyl)-3,15-
dioxa-10-azatetracyclo[8.7.0.01,13.04,9]heptadeca-
4,6,8,13-tetraene-2,11,12-trione (VId) and
(1R*,16R*)-16-butoxy-14-(4-ethoxyphenyl)-3,15-
dioxa-10-azatetracyclo[8.7.0.01,13.04,9]heptadeca-
4,6,8,13-tetraene-2,11,12-trione (VIId). A solution of
5.0 mmol of butyl vinyl ether in 5 mL of anhydrous
benzene was added to a solution of 1.0 mmol of
compound Ib in 20 mL of anhydrous benzene, and the
mixture was heated for 50 min under reflux (until
violet color disappeared). The mixture was cooled, and
the yellow precipitate was filtered off. Yield 88%,
mp 186–188°C (decomp., from benzene). IR spectrum,
1
ν, cm–1: 1788 (C2=O), 1724 (C11=O, C12=O). H NMR
spectrum, δ, ppm: 1.11 t (3H, CH3, J = 7.0 Hz),
2.41 d.d (1H, 17-H, J = 4.4, 13.6 Hz), 2.45 d.d (1H,
17-H, J = 14.0, 0.8 Hz), 3.72 m and 3.82 m (2H,
OCH2), 5.80 d.d (1H, CH, J = 4.0, 0.8 Hz), 7.37–
7.90 m (7H, Harom). Found, %: C 62.22; H 3.83;
Cl 8.26; N 3.21. C22H16ClNO6. Calculated, %:
C 62.05; H 3.79; Cl 8.33; N 3.29.
(1R*,16R*)-7-Chloro-16-ethoxy-14-phenyl-3,15-
dioxa-10-azatetracyclo[8.7.0.01,13.04,9]heptadeca-
4,6,8,13-tetraene-2,11,12-trione (VIIc). Yield 21%,
mp 237–239°C (decomp., from benzene). IR spectrum,
1
ν, cm–1: 1798 (C2=O), 1728 (C11=O, C12=O). H NMR
1
ν, cm–1: 1777 (C2=O), 1730 (C11=O, C12=O). H NMR
spectrum, δ, ppm: 1.22 t (3H, CH3, J = 7.0 Hz),
2.19 d.d (1H, 17-H, J = 4.2, 13.0 Hz), 2.68 d.d (1H,
17-H, J = 10.2, 13.0 Hz), 3.80 m and 4.06 m (2H,
OCH2), 5.60 d.d (1H, CH, J = 4.4, 10.0 Hz), 7.37–
7.86 m (7H, Harom). Found, %: C 62.19; H 3.75;
Cl 8.30; N 3.35. C22H16ClNO6. Calculated, %:
C 62.05; H 3.79; Cl 8.33; N 3.29.
spectrum, δ, ppm: VId: 0.83 t (3H, CH2CH2CH2CH3,
J = 7.4 Hz), 1.29 m (2H, CH2CH2CH2CH3), 1.39 t
(3 H , O C H 2 C H 3 , J = 7 . 0 H z ) , 1 . 4 7 m ( 2 H,
CH2CH2CH2CH3), 2.35 d.d. (1H, 17-H, J = 4.0,
13.4 Hz), 2.40 d.d (1H, 17-H, J = 1.4, 13.4 Hz), 3.64 m
and 3.79 m (2H, OCH2), 4.17 m (2H, OCH2CH3),
5.73 d.d (1H, CH, J = 1.4, 4.2 Hz), 6.90–8.00 m (8H,
Harom); VIId: 0.89 t (3H, CH2CH2CH2CH3, J =
7.2 Hz), 1.37 m (2H, CH2CH2CH2CH3), 1.39 t (3H,
OCH2CH3, J = 7.0 Hz), 1.57 m (2H, CH2CH2CH2-
CH3), 2.19 d.d (1H, 17-H, J = 9.8, 13.0 Hz), 2.79 d.d
(1H, 17-H, J = 4.2, 12.8 Hz), 3.66 m and 4.01 m (2H,
OCH2), 4.17 m (2H, OCH2CH3), 5.56 d.d (1H, CH, J =
4.0, 10.2 Hz), 6.90–7.88 m (8H, Harom); signal intensity
ratio ~10:1. Found, %: C 67.46; H 5.47; N 3.11.
C26H25NO7. Calculated, %: C 67.38; H 5.44; N 3.02.
X-Ray diffraction data for compound VIc. Light
yellow well faceted tetragonal prisms; C22H16ClNO6;
triclinic crystal system; unit cell parameters: a =
6.758(1), b = 10.562(1), c = 14.603(2) Å; α = 95.85(1),
β = 101.44(1), γ = 106.05(1)°; V = 968.1(2) Å3;
M 425.81; dcalc = 1.461 g/cm3; Z = 2; space group P-1.
A set of experimental reflection intensities was
acquired on a KM-4 (KUMA Diffraction) automatic
four-circle diffractometer with χ-geometry by ω/2Θ
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 12 2013

STEPANOVA et al.
1766
Compounds VIe–VIi and VIIe–VIIi were synthe-
1.38 t (3H, C6H4OCH2CH3, J = 7.0 Hz), 2.34 d.d (1H,
sized in a similar way.
17-H, J = 4.0, 13.6 Hz), 2.39 d.d (1H, 17-H, J = 2.6,
12.4 Hz), 3.71 m and 3.83 m (2H, OCH2Me), 4.18 q
(2H, C6H4OCH2CH3, J = 6.9 Hz), 5.75 d.d (1H, CH,
J = 1.8, 3.8 Hz), 7.10–8.00 m (8H, Harom); VIIg: 1.21 t
(3H, CH3, J = 7.2 Hz), 1.38 t (3H, C6H4OCH2CH3, J =
7.0 Hz), 2.13 d.d (1H, 17-H, J = 10.2, 12.8 Hz),
2.62 d.d (1H, 17-H, J = 4.2, 13.0 Hz), 3.83 m and
4.06 m (2H, OCH2Me), 4.18 q (2H, C6H4OCH2CH3,
J = 6.9 Hz), 5.58 d.d (1H, CH, J = 4.0, 10.2 Hz), 7.10–
7.89 m (8H, Harom); signal intensity ratio ~10:1.
Found, %: C 66.29; H 4.84; N 3.19. C24H21NO7. Cal-
culated, %: C 66.20; H 4.86; N 3.22.
(1S*,16R*)-16-Ethoxy-14-(4-nitrophenyl)-3,15-
dioxa-10-azatetracyclo[8.7.0.01,13.04,9]heptadeca-
4,6,8,13-tetraene-2,11,12-trione (VIe) and
(1R*,16R*)-16-ethoxy-14-(4-nitrophenyl)-3,15-
dioxa-10-azatetracyclo[8.7.0.01,13.04,9]heptadeca-
4,6,8,13-tetraene-2,11,12-trione (VIIe). Yield 87%,
mp 236–240°C (decomp., from toluene). IR spectrum,
ν, cm–1: 1802 (C2=O), 1731 (C11=O, C12=O). H NMR
1
spectrum, δ, ppm: VIe: 1.11 t (3H, CH3, J = 7.0 Hz),
2.40 d.d (1H, 17-H, J = 3.2, 13.0 Hz), 2.43 d.d (1H,
17-H, J = 2.4, 13.0 Hz), 3.72 m and 3.82 m (2H,
OCH2), 5.84 d.d (1H, CH, J = 2.4, 3.2 Hz), 6.95–
8.43 m (8H, Harom); VIIe: 1.21 t (3H, CH3, J = 7.2 Hz),
2.26 d.d (1H, 17-H, J = 10.0, 13,2 Hz), 2.62 d.d (1H,
17-H, J = 3.8, 12,6 Hz), 3.81 m and 4.05 m (2H,
OCH2), 5.64 d.d (1H, CH, J = 4.0, 10.4 Hz), 6.95–
8.34 m (8H, Harom); signal intensity ratio ~5:3. Found,
%: C 60.58; H 3.64; N 6.55. C22H16N2O8. Calculated,
%: C 60.55; H 3.70; N 6.42.
(1S*,16R*)-14-(4-Bromophenyl)-16-ethoxy-3,15-
dioxa-10-azatetracyclo[8.7.0.01,13.04,9]heptadeca-
4,6,8,13-tetraene-2,11,12-trione (VIh) and
(1R*,16R*)-14-(4-bromophenyl)-16-ethoxy-3,15-
dioxa-10-azatetracyclo[8.7.0.01,13.04,9]heptadeca-
4,6,8,13-tetraene-2,11,12-trione (VIIh). Yield 93%,
mp 238–240°C (decomp., toluene). IR spectrum, ν,
1
cm–1: 1794 (C2=O), 1728 (C11=O, C12=O). H NMR
spectrum, δ, ppm: VIh: 1.11 t (3H, CH3, J = 7.2 Hz),
2.36 d.d (1H, 17-H, J = 3.6, 14.0 Hz), 2.41 d.d (1H,
17-H, J = 2.2, 11.6 Hz), 3.71 m and 3.82 m (2H,
OCH2), 5.78 d.d (1H, CH, J = 2.4, 3.2 Hz), 7.32–
7.87 m (8H, Harom); VIIh: 1.21 t (3H, CH3, J = 7.0 Hz),
2.18 d.d (1H, 17-H, J = 10.2, 12.8 Hz), 2.61 d.d (1H,
17-H, J = 4.2, 13.0 Hz), 3.84 m and 4.04 m (2H,
OCH2), 5.62 d.d (1H, CH, J = 4.2, 10.2 Hz), 7.32–
7.78 m (8H, Harom); signal intensity ratio ~10:1. Found,
%: C 55.98; H 3.48; Br 17.09; N 3.01. C22H16BrNO6.
Calculated, %: C 56.19; H 3.43; Br 16.99; N 2.98.
(1S*,16R*)-16-Ethoxy-14-(4-methoxyphenyl)-
3,15-dioxa-10-azatetracyclo[8.7.0.01,13.04,9]hepta-
deca-4,6,8,13-tetraene-2,11,12-trione (VIf) and
(1R*,16R*)-16-ethoxy-14-(4-methoxyphenyl)-3,15-
dioxa-10-azatetracyclo[8.7.0.01,13.04,9]heptadeca-
4,6,8,13-tetraene-2,11,12-trione (VIIf). Yield 93%,
mp 234–236°C (decomp., from toluene). IR spectrum,
1
ν, cm–1: 1771 (C2=O), 1715 (C11=O, C12=O). H NMR
spectrum, δ, ppm: VIf: 1.11 t (3H, CH2CH3, J =
7.0 Hz), 2.35 d.d (1H, 17-H, J = 4.4, 14.0 Hz), 2.40 d.d
(1H, 17-H, J = 2.8, 13.5 Hz), 3.71 m and 3.81 m (2H,
OCH2), 3.90 s (3H, OCH3), 5.75 d.d (1H, CH, J = 2.0,
3.6 Hz), 7.11–8.00 m (8H, Harom); VIIf: 1.21 t (3H,
Me, J = 7.0 Hz), 2.14 d.d (1H, 17-H, J = 10.4,
12.8 Hz), 2.61 d.d (1H, 17-H, J = 4.4, 13.2 Hz), 3.80 m
and 4.06 m (2H, OCH2), 3.90 s (3H, OCH3), 5.58 d.d
(1H, CH, J = 4.4, 10.4 Hz), 7.11–7.90 m (8H, Harom);
signal intensity ratio ~5:1. Found, %: C 65.59; H 4.57;
N 3.35. C23H19NO7. Calculated, %: C 65.55; H 4.54;
N 3.32.
(1S*,16R*)-14-(3-Bromophenyl)-16-butoxy-7-
chloro-3,15-dioxa-10-azatetracyclo[8.7.0.01,13.04,9]-
heptadeca-4,6,8,13-tetraene-2,11,12-trione (VIi) and
(1R*,16R*)-14-(3-bromophenyl)-16-butoxy-7-
chloro-3,15-dioxa-10-azatetracyclo[8.7.0.01,13.04,9]-
heptadeca-4,6,8,13-tetraene-2,11,12-trione (VIIi).
Yield 87%, mp 226–228°C (decomp., from benzene).
IR spectrum, ν, cm–1: 1792 (C2=O), 1730 (C11=O,
1
C12=O). H NMR spectrum, δ, ppm: VIi: 0.83 t (3H,
(1S*,16R*)-16-Ethoxy-14-(4-ethoxyphenyl)-3,15-
dioxa-10-azatetracyclo[8.7.0.01,13.04,9]heptadeca-
4,6,8,13-tetraene-2,11,12-trione (VIg) and
(1R*,16R*)-16-ethoxy-14-(4-ethoxyphenyl)-3,15-
dioxa-10-azatetracyclo[8.7.0.01,13.04,9]heptadeca-
4,6,8,13-tetraene-2,11,12-trione (VIIg). Yield 91%,
mp 202–204°C (decomp., from toluene). IR spectrum,
CH3, J = 7.4 Hz), 1.29 m (2H, CH2Me), 1.46 m (2H,
CH2Et), 2.37 d.d (1H, 17-H, J = 4.0, 13.6 Hz), 2.42 d.d
(1H, 17-H, J = 1.6, 12.8 Hz), 3.67 m and 3.78 m (2H,
OCH2), 5.79 d.d (1H, CH, J = 1.4, 3.8 Hz), 7.39–
8.04 m (7H, Harom); VIIi: 0.90 t (3H, CH3, J = 7.4 Hz),
1.36 m (2H, CH2Me), 1.57 m (2H, CH2Et), 2.21 d.d
(1H, 17-H, J = 10.8, 12.8 Hz), 2.69 d.d (1H, 17-H, J =
4.0, 13.2 Hz), 3.79 m and 3.99 m (2H, OCH2), 5.60 d.d
(1H, CH, J = 3.8, 10.2 Hz), 7.37–7.94 m (7H, Harom);
1
ν, cm–1: 1794 (C2=O), 1728 (C11=O, C12=O). H NMR
spectrum, δ, ppm: VIg: 1.11 t (3H, CH3, J = 7.0 Hz),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 12 2013

FIVE-MEMBERED 2,3-DIOXO HETEROCYCLES: XCVIII.
1767
6. Tsuda, Y., Horiguchi, Y., and Sano, T., Heterocycles,
signal intensity ratio ~2:1. Found, %: C 54.17; H 3.58;
N 2.65. C24H19BrClNO6. Calculated, %: C 54.11;
H 3.59; N 2.63.
1976, vol. 4, p. 1355.
7. Maslivets, A.N., Mashevskaya, I.V., Krasnykh, O.P.,
Shurov, S.N., and Andreichikov, Yu.S., Zh. Org. Khim.,
1992, vol. 28, p. 2545.
8. Maslivets, V.A. and Maslivets, A.N., Russ. J. Org.
Chem., 2012, vol. 48, p. 1233.
9. Stepanova, E.E., Babenysheva, A.V., and Masli-
vets, A.N., Russ. J. Org. Chem., 2011, vol. 47, p. 937.
10. Andreichikov, Yu.S., Voronova, L.A., and Kozlov, A.P.,
This study was performed under financial support
by the Ministry of Education and Science of the
Russian Federation, by the Ministry of Education of
Perm Krai (International Research Teams Com-
petition), and by the Russian Foundation for Basic
Research (project nos. 12-03-00696, 12-03-31157,
13-03-96009).
Zh. Org. Khim., 1979, vol. 15, p. 520.
11. Stepanova, E.E., Babenysheva, A.V., and Masli-
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 12 2013