Five-membered 2,3-dioxo heterocycles: LXIX. Direct heterocyclization of [3,4-dihydroisoquinolin-1(2H)-ylidene]-acetamides with 5-arylfuran-2,3-diones. Crystalline and molecular structure of (3E,5Z)-3-[3,3-dimethyl-3,4- dihydroisoquinolin-1(2H)-ylidene]-5-

Article abstract of DOI:10.1134/S1070428010040159

5-Arylfuran-2,3-diones react with (Z)-2-[3,3-dimethyl-3,4- dihydroisoquinolin-1(2H)-ylidene]acetamides to give (3E,5Z)-5-(2-aryl-2- oxoethylidene)-3-[3,3-dimethyl-3,4-dihydroisoquinolin-1(2H)-ylidene] -pyrrolidine-2,4-diones. The crystalline and molecular

Full text of DOI:10.1134/S1070428010040159

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 4, pp. 539–542. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © V.V. Khalturina, Yu.V. Shklyaev, Z.G. Aliev, A.N. Maslivets, 2010, published in Zhurnal Organicheskoi Khimii, 2010, Vol. 46,
No. 4, pp. 548–551.
Five-Membered 2,3-Dioxo Heterocycles: LXIX.* Direct
Heterocyclization of [3,4-Dihydroisoquinolin-1(2H)-ylidene]-
acetamides with 5-Arylfuran-2,3-diones. Crystalline
and Molecular Structure of (3E,5Z)-3-[3,3-Dimethyl-
3,4-dihydroisoquinolin-1(2H)-ylidene]-5-(2-oxo-
2-phenylethylidene)pyrrolidine-2,4-dione
V. V. Khalturinaa, Yu. V. Shklyaeva, Z. G. Alievb, and A. N. Maslivetsc
a Institute of Technical Chemistry, Ural Division, Russian Academy of Sciences,
ul. Akademika Koroleva 3, Perm, 614013 Russia
b Institute of Chemical Physics Problems, Russian Academy of Sciences, Chernogolovka, Moscow oblast, Russia
c Perm State University, ul. Bukireva 15, Perm, 614990 Russia
e-mail: koh2@psu.ru
Received May 6, 2009
Abstract—5-Arylfuran-2,3-diones react with (Z)-2-[3,3-dimethyl-3,4-dihydroisoquinolin-1(2H)-ylidene]acet-
amides to give (3E,5Z)-5-(2-aryl-2-oxoethylidene)-3-[3,3-dimethyl-3,4-dihydroisoquinolin-1(2H)-ylidene]-
pyrrolidine-2,4-diones. The crystalline and molecular structures of one of the products were determined by
X-ray analysis.
DOI: 10.1134/S1070428010040159
We previously described acylation of substituted
1-methyl-3,4-dihydroisoquinolines at the β-CH group
of enamino tautomer with 5-arylfuran-2,3-diones,
which led to the formation of (2Z,5Z)-1-aryl-3-hy-
droxy-5-[3,3-dimethyl-3,4-dihydroisoquinolin-1(2H)-
ylidene]pent-2-ene-1,4-diones whose structure was
proved by X-ray analysis [2]. In the present work we
examined reactions of 5-arylfuran-2,3-diones with sub-
stituted [3,4-dihydroisoquinolin-1(2H)-ylidene]acet-
amides. The latter possess three nucleophilic centers,
β-CH and NH groups in the enamine moiety and amide
NH2 group. Initial electrophilic attack at one of these
centers should determine the structure of the final
product.
5-Aryl-2,3-dihydrofuran-2,3-diones Ia–Ic reacted
with (Z)-2-[3,3-dimethyl-3,4-dihydroisoquinolin-
1(2H)-ylidene]acetamides IIa and IIb at a reactant
molar ratio of 1:1 on heating in boiling anhydrous
benzene over a period of 1–2 h. The progress of the
reactions was monitored by thin-layer chromatography,
and the products were 5-(2-aryl-2-oxoethylidene)-3-
[3,3-dimethyl-3,4-dihydroisoquinolin-1(2H)-ylidene]-
pyrrolidine-2,4-diones IIIa–IIIf (Scheme 1). However,
we failed to unambiguously determine their steric
structure (specifically configuration of two exocyclic
double bonds) on the basis of their spectral data.
Therefore, compound IIIa was examined by X-ray dif-
fraction which unambiguously showed that compounds
IIIa–IIIf have the structure of (3E,5Z)-5-(2-aryl-2-
oxoethylidene)-3-[3,3-dimethyl-3,4-dihydroisoquino-
lin-1(2H)-ylidene]pyrrolidine-2,4-diones IIIa–IIIf.
Compounds IIIa–IIIf were isolated as yellow crys-
talline substances which melted with decomposition;
they are readily soluble in dimethyl sulfoxide and di-
methylformamide, poorly soluble in other common
organic solvents, and insoluble in water and saturated
hydrocarbons.
The IR spectra of IIIa–IIIf contained broadened
absorption band in the regions 3250–3383 and 3150–
3195cm–1 due to stretching vibrations of the NH group
in the isoquinoline and pyrrole fragments, involved in
* For communication LXVIII, see [1].
539

KHALTURINA et al.
540
Scheme 1.
Me
Me
Me
Me
Me
Me
R
R
NH
N
O
NH
O
O
O
O
O
+
Ar
O
O
NH2
O
NH2
O
O
H
O
NH2
IIa, IIb
Ar
Ar
Ia–Ic
Me
Me
Me
O
NH
Ar
Me
NH
O
O
O
NH
–H2O
H2N
O
O
O
Ar
IIIa–IIIf
I, Ar = Ph (a), 4-MeC6H4 (b), 4-ClC6H4 (c); II, R = H (a), MeO (b); III, Ar = Ph, R = H (a), MeO (b);
Ar = 4-MeC6H4, R = H (c), MeO (d); Ar = 4-ClC6H4, R = H (e), MeO (f).
intramolecular hydrogen bonds; ketone carbonyl group
(C2=O) gave rise to absorption at 1661–1682 cm–1, and
stretching vibrations of the C4=O and aroyl carbonyl
groups (both involved in intramolecular hydrogen
bond) appeared at 1625–1635 and 1587–1611 cm–1,
respectively. Compounds IIIa–IIIf displayed in the
1H NMR spectra (DMSO-d6) signals from protons in
aromatic rings and substituents attached thereto, a sin-
glet from six protons in the geminal methyl groups on
C3 in the isoquinoline fragment (δ 1.29–1.30 ppm),
a singlet from methylene protons on C4 (δ 2.93–
3.00 ppm), a singlet from the vinylic proton (δ 6.66–
6.69 ppm), and two downfield singlets from the NH
protons in the isoquinoline and pyrrole rings at
δ 10.26–10.41 and 11.22–11.25 ppm, respectively.
C11
C10
C12
C7
C6
Figure 1 shows the structure of molecule IIIa ac-
cording to the X-ray diffraction data. Molecule IIIa is
stabilized by two intramolecular hydrogen bonds like
NH···O: N1–H1···O3 (N1···O3 2.727 Å) and N2–H2···O2
(N2 ···O2 2.738 Å). The carbonyl group in the phen-
acylidene fragment lies in the pyrrole ring plane,
giving rise to a common conjugation system, while the
benzene ring is turned through a dihedral angle of
37.3° with respect to the pyrrole ring plane (the torsion
angle O3C6C7C8 is equal to –32.2°). The N2 and C21
atoms deviate by 0.56 and 0.96 Å, respectively, from
the plane formed by the other atoms of the isoquino-
line fragment which forms a dihedral angle of 35.1°
with the pyrrole ring plane. The torsion angles
C1C2C13C14 and N2C13C2C3 are 21.4 and 11.9°, respec-
tively. All interatomic distances are usual for the cor-
responding bonds. The crystal packing of compound
IIIa is characterized by shortened [3] intermolecular
contact between the C4 and C4′ atoms (3.24 Å) related
C23
O2
C3
C9
H2
C5
C4
C8
O3
N2
C21
C22
C13
C14
N1
C2
C20
C19
H1
C1
O1
C15
C18
C16
C17
Fig. 1. Structure of the molecule of (3E,5Z)-3-[3,3-dimethyl-
3,4-dihydroisoquinolin-1(2H)-ylidene]-5-(2-oxo-2-phenyl-
ethylidene)pyrrolidine-2,4-dione (IIIa) according to the
X-ray diffraction data.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 4 2010

FIVE-MEMBERED 2,3-DIOXO HETEROCYCLES: LXIX.
to each other through a symmetry center. This distance
541
almost coincides with the distance between the central
planar fragments of symmetry-related molecules
(Fig. 2). Thus the crystalline structure of compound
IIIa is formed by couples of its molecules, which are
likely to be involved in additional intermolecular
π interaction. No other shortened molecular contacts
were found in crystal.
Presumably, in the first step the β-CH group in the
enamino fragment of isoquinolines IIa and IIb under-
goes acylation by the C2=O group of 5-arylfuran-2,3-
dione Ia–Ic with subsequent opening of the furan ring
at the O1–C2 bond, as reported previously for the re-
actions of the same furandiones with oxygen-, sulfur-,
and nitrogen-centered mono- and difunctional nucleo-
philes [4]. Next follows Z–E-isomerization at the exo-
cyclic double C=C bond (Scheme 1) and intramolec-
ular cyclization with elimination of water molecule.
Fig. 2. Dimeric associate of (3E,5Z)-3-[3,3-dimethyl-3,4-di-
hydroisoquinolin-1(2H)-ylidene]-5-(2-oxo-2-phenylethyli-
dene)pyrrolidine-2,4-dione (IIIa) in crystal.
(C4′), 89.62 (C3′), 91.63 (C3), 123.63 (C1), 126.13–
137.98 (Carom), 146.17 (C5), 160.97 (C1′), 172.27 (C2),
182.86 (C4), 190.15 (COPh). Found, %: C 74.03;
H 5.53; N 7.33. C23H20N2O3. Calculated, %: C 74.18;
H 5.41; N 7.52.
The described reaction may be regarded as an ex-
ample of synthesis of a stereoregular ensemble from
two polyfunctional heterocyclic systems, as well as of
direct heterocyclization of hetarylideneacetamides with
5-arylfuran-2,3-diones.
Compounds IIIb–IIIf were synthesized in a similar
way.
(3E,5Z)-3-[6,7-Dimethoxy-3,3-dimethyl-3,4-di-
hydroisoquinolin-1(2H)-ylidene]-5-(2-oxo-2-phenyl-
ethylidene)pyrrolidine-2,4-dione (IIIb). Yield 83%,
mp 93–95°C (decomp., from ethanol). IR spectrum, ν,
cm–1: 3319 br, 3186 br (NH); 1674 (C2=O); 1631 br
EXPERIMENTAL
1
(C4=O); 1588 br (PhCO). H NMR spectrum, δ, ppm:
The IR spectra were recorded on an FSM-1201
spectrometer from samples dispersed in mineral oil.
1.30 s (6H, Me), 2.93 s (2H, 4′-H), 3.82 s (3H, OMe),
3.89 s (3H, OMe), 6.69 s (1H, CH), 6.99–8.12 m (7H,
1
The H and 13C NMR spectra were measured on
a Bruker AM-400 spectrometer operating at 400 MHz;
DMSO-d6 was used as solvent, and tetramethylsilane,
as internal reference. The purity of the isolated com-
pounds was checked by thin-layer chromatography on
Silufol plates using ethyl acetate–benzene (1:5) or
ethyl acetate as eluent; spots were visualized by treat-
ment with iodine vapor.
H
arom), 10.31 s (1H, 2′-H), 11.25 s (1H, 1-H). Found,
%: C 69.37; H 5.59; N 6.31. C25H24N2O5. Calculated,
%: C 69.43; H 5.59; N 6.48.
(3E,5Z)-3-[3,3-Dimethyl-3,4-dihydroisoquinolin-
1(2H)-ylidene]-5-[2-(4-methylphenyl)-2-oxoethyli-
dene]pyrrolidine-2,4-dione (IIIc). Yield 88%,
mp 223–225°C (decomp., from benzene). IR spectrum,
ν, cm–1: 3250 br, 3195 br (NH); 1682 (C2=O); 1632 br
(3E,5Z)-3-[3,3-Dimethyl-3,4-dihydroisoquinolin-
1(2H)-ylidene]-5-(2-oxo-2-phenylethylidene)pyrroli-
dine-2,4-dione (IIIa). A solution of 2.0 mmol of
5-phenyl-2,3-dihydrofuran-2,3-dione (Ia) and
2.0 mmol of isoquinolinylideneacetamide IIa in 20 ml
of anhydrous toluene was heated for 2 h under reflux.
The mixture was cooled, and the precipitate was
filtered off. Yield 0.60 g (85%), mp 166–168°C
(decomp., from ethanol). IR spectrum, ν, cm–1:
3383 br, 3190 br (NH); 1661 (C2=O); 1625 br (C4=O);
(C4=O); 1608 br (ArCO). H NMR spectrum, δ, ppm:
1
1.29 s (6H, Me), 2.40 s (3H, CH3C6H4), 2.97 s (2H,
4′-H), 6.67 s (1H, CH), 7.13–8.30 m (8H, Harom),
10.32 s (1H, 2′-H), 11.25 s (1H, 1-H). Found, %:
C 74.48; H 5.79; N 7.11. C24H22N2O3. Calculated, %:
C 74.59; H 5.74; N 7.25.
(3E,5Z)-3-[6,7-Dimethoxy-3,3-dimethyl-3,4-di-
hydroisoquinolin-1(2H)-ylidene]-5-[2-(4-methyl-
phenyl)-2-oxoethylidene]pyrrolidine-2,4-dione
(IIId). Yield 87%, mp 111–113°C (decomp., from
ethanol). IR spectrum, ν, cm–1: 3336 br, 3180 br (NH);
1678 (C2=O); 1633 br (C4=O); 1611 br (ArCO).
1H NMR spectrum, δ, ppm: 1.30 s (6H, Me), 2.35 s
1
1594 br (PhCO). H NMR spectrum, δ, ppm: 1.29 s
(6H, Me), 3.00 s (2H, 4′-H), 6.69 s (1H, CH), 7.37–
8.30 m (9H, Harom), 10.37 s (1H, 2′-H), 11.25 s (1H,
1-H). 13C NMR spectrum, δC, ppm: 26.05 (Me), 50.96
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 4 2010

KHALTURINA et al.
542
(3H, CH3C6H4), 2.93 s (2H, 4′-H), 3.82 s (3H, OMe),
measured, 2742 of which were independent (Rint =
3.89 s (3H, OMe), 6.67 s (1H, CH), 6.99–8.12 m (6H,
0.0228). No correction for absorption was introduced
(μ = 0.087 mm–1). The structure was solved by the
direct method using SIR92 program [5], followed by
a series of calculation of electron density maps. Hydro-
gen atoms on the nitrogen atoms and C5 were visual-
ized by difference synthesis, while the positions of the
other hydrogen atoms were set on the basis of geom-
etry considerations and were refined according to the
riding model. The positions of non-hydrogen atoms
were refined by the least-squares procedure in full-
matrix anisotropic approximation using SHELXL-97
software [6]; the final divergence factors were R1 =
0.0418, wR2 = 0.0964 [for 2004 reflections with I ≥
2σ(I)] and R1 = 0.0673, wR2 = 0.1089 (for all reflec-
tions); 265 refined parameters; goodness of fit 1.052.
Harom), 10.26 s (1H, 2′-H), 11.25 s (1H, 1-H). Found,
%: C 69.93; H 6.07; N 6.09. C26H26N2O5. Calculated,
%: C 69.94; H 5.87; N 6.27.
(3E,5Z)-5-[2-(4-Chlorophenyl)-2-oxoethylidene]-
3-[3,3-dimethyl-3,4-dihydroisoquinolin-1(2H)-
ylidene]pyrrolidine-2,4-dione (IIIe). Yield 85%,
mp 201–203°C (decomp., from ethanol). IR spectrum,
ν, cm–1: 3288 br, 3150 br (NH); 1675 (C2=O); 1629 br
1
(C4=O); 1587 br (ArCO). H NMR spectrum, δ, ppm:
1.29 s (6H, Me), 3.00 s (2H, 4′-H), 6.66 s (1H, CH),
7.34–8.28 m (8H, Harom), 10.41 s (1H, 2′-H), 11.22 s
(1H, 1-H). Found, %: C 67.78; H 4.73; N 6.94.
C23H19ClN2O3. Calculated, %: C 67.90; H 4.71; N 6.89.
(3E,5Z)-5-[2-(4-Chlorophenyl)-2-oxoethylidene]-
3-[6,7-dimethoxy-3,3-dimethyl-3,4-dihydroisoquin-
olin-1(2H)-ylidene]pyrrolidine-2,4-dione (IIIf).
Yield 86%, mp 150–152°C (decomp., from ethanol).
IR spectrum, ν, cm–1: 3341 br, 3190 br (NH); 1678
This study was performed under financial support
by the Russian Foundation for Basic Research (project
nos. 08-03-01032, 07-03-96036, 07-03-00001).
1
(C2=O); 1635 br (C4=O); 1589 br (ArCO). H NMR
REFERENCES
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3.82 s (3H, OMe), 3.89 s (3H, OMe), 6.69 s (1H, CH),
7.00–8.10 m (6H, Harom), 10.35 s (1H, 2′-H), 11.22 s
(1H, 1-H). Found, %: C 64.23; H 5.04; N 5.99.
C25H23ClN2O5. Calculated, %: C 64.31; H 4.96; N 6.00.
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well defined tetrahedral prisms, C23H20N2O3; mono-
clinic crystal system; unit cell parameters: a =
15.570(2), b = 15.629(2), c = 16.988(2) Å; β =
113.42(1)°; V = 3793.3(8) Å3; M 372.41; dcalc
=
1.304 g/cm3; Z = 8; space group C2/c. Experimental
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scanning, 2Θ ≤ 50.0°). Total of 3382 reflections were
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 4 2010