Acylation of the enamino tautomer of 2-azaspiro[4.5]deca-1,6,9-trien-8-ones with 5-arylfuran-2,3-diones. Crystal and molecular structure of (2Z,5Z)-3-Hydroxy-5-(6,9-dimethoxy-3,3-dimethyl-8-oxo-2-azaspiro[4.5]deca-6,9-dien-1-ylidene)-1-phenylpent-2-ene-1,

Article abstract of DOI:10.1134/S1070428014120112

5-Arylfuran-2,3-diones reacted with heterocyclic enamines of the 2-azaspiro[4.5]deca-1,6,9-trien-8-one series to give products of β-CH-acylation of the enamino fragment. The structure of (2Z,5Z)-3-hydroxy-5-(6,9-dimethoxy-3,3-dimethyl-8-oxo-2-azaspiro[4.5

Full text of DOI:10.1134/S1070428014120112

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2014, Vol. 50, No. 12, pp. 1779–1782. © Pleiades Publishing, Ltd., 2014.
Original Russian Text © V.V. Konovalova, Yu.S. Rozhkova, Yu.V. Shklyaev, P.A. Slepukhin, A.N. Maslivets, 2014, published in Zhurnal Organicheskoi
Khimii, 2014, Vol. 50, No. 12, pp. 1798–1801.
Acylation of the Enamino Tautomer of 2-Azaspiro[4.5]deca-
1
,6,9-trien-8-ones with 5-Arylfuran-2,3-diones. Crystal
and Molecular Structure of (2Z,5Z)-3-Hydroxy-5-(6,9-dimethoxy-
,3-dimethyl-8-oxo-2-azaspiro[4.5]deca-6,9-dien-1-ylidene)-
-phenylpent-2-ene-1,4-dione
3
1
a
a
a
b
c
V. V. Konovalova , Yu. S. Rozhkova , Yu. V. Shklyaev , P. A. Slepukhin , and A. N. Maslivets
a
Institute of Technical Chemistry, Ural Branch, Russian Academy of Sciences,
ul. Akademika Koroleva 3, Perm, 614013 Russia
e-mail: conovalova.val@yandex.ru
b
Postovskii Institute of Organic Synthesis, Ural Branch, Russian Academy of Sciences,
ul. S. Kovalevskoi/Akademicheskaya 22/20, Yekaterinburg, 620990 Russia
c
Perm State National Research University, ul. Bukireva 15, Perm, 614990 Russia
Received February 25, 2014
Abstract—5-Arylfuran-2,3-diones reacted with heterocyclic enamines of the 2-azaspiro[4.5]deca-1,6,9-trien-8-
one series to give products of β-CH-acylation of the enamino fragment. The structure of (2Z,5Z)-3-hydroxy-5-
(
6,9-dimethoxy-3,3-dimethyl-8-oxo-2-azaspiro[4.5]deca-6,9-dien-1-ylidene)-1-phenylpent-2-ene-1,4-dione was
proved by X ray analysis.
DOI: 10.1134/S1070428014120112
Thermal decarbonylation of 5-arylfuran-2,3-diones
generates aroylketenes capable of reacting with active
dienophiles according to the Diels–Alder pattern [1, 2]
and acylating weak nucleophiles with formation of
aroylacetyl derivatives [1, 3]. On the other hand, furan-
diones themselves can react with nucleophiles to pro-
duce aroylpyruvoyl derivatives at a temperature below
that required for generation of aroylketenes [1, 4]. We
previously showed that some heterocyclic enamines of
the 1-methyl-3,4-dihydroisoquinoline, 1-methyl-2-aza-
spiro[4.5]deca-1,6,9-trien-8-one, and 2-methylidene-
at a molar ratio of 1:1 on heating in boiling benzene
(3–6 h, TLC monitoring) to afford (2Z,5Z)-1-aryl-3-
hydroxy-5-(5′,5′-dimethyl-4-oxo-2′H,4H-spiro[naph-
thalene-1,3′-pyrrolidin]-2′-ylidene)pent-2-ene-1,4-di-
ones IIIa and IIIb and substituted (2Z,5Z)-3-hydroxy-
5-(3,3-dimethyl-8-oxo-2-azaspiro[4.5]deca-6,9-dien-1-
ylidene)-1-phenylpent-2-ene-1,4-diones IIIc–IIIe
(Scheme 1). The structure of compound IIIe was
confirmed by X-ray analysis.
Compounds IIIa–IIIe were isolated as light yellow
(
almost colorless) high-melting crystalline substances
1
,3,3-trimethyl-2,3-dihydro-1H-indole (Fisher’s base)
which were readily soluble in DMSO and DMF, poorly
soluble in alcohols, ethers, and haloalkanes, and insol-
uble in alkanes and water. They showed a positive test
series can be acylated with 5-arylfuran-2,3-diones to
give the corresponding aroylpyruvoyl derivatives
[
5
[
5–7]. In continuation of our studies on the reactions of
-arylfuran-2,3-diones with spirans of the 2-azaspiro-
4.5]deca-1,6,9-trien-8-one series in the present work
(
cherry color) for enolic hydroxy group on treatment
with an alcoholic solution of iron(III) chloride.
The IR spectra of IIIa–IIIe contained absorption
bands due to stretching vibrations of enolic hydroxy
group and NH group involved in intramolecular hydro-
we examined how additional substituents in positions 3
and 6 of the latter affect the direction of their reaction
with the former.
–1
gen bonds (broad band at 3150–3261 cm ), ketone
4
8
5
-Arylfuran-2,3-diones Ia and Ib reacted with
carbonyl group (C =O in IIIa, IIIb or C =O in IIIc–
–
1
2
-azaspiro[4.5]deca-1,6,9-trien-8-ones IIa–IId [8–10]
IIIe; 1660–1664 cm ), and carbonyl groups in posi-
1
779

1
780
KONOVALOVA et al.
Scheme 1.
O
O
R1
R2
R1
R4
Me
R2
3
3
R4
R
R
Me
CH
2
N
NH
Me
Me
Me
IIa–IId
A
O
O
8
0–81°C, 3–4 h
H
·
O
··
O
O
O
O
N
N
Ar
Ar
Ar
O
Me
R1
· O
Me
· O
· ·
H·
·
O
H
Me
Me
Ia, Ib
B
IIIa, IIIb
C
O
O
R2
R3
R1
R2
R3
8
0–81°C, 3–6 h
H
·
O
··
O
O
O
N
N
Ph
Ph
O
O
· ·
·
Me
·
Me
·
·
H
H
Me
Me
B
IIIc–IIIe
C
1
4
2
3
1
2
3
4
1
2
4
3
I, Ar = Ph (a), 4-MeC
6
H
4
(b); II, R R = benzo, R = R = H (a); R = R = Me, R = R = H (b); R = MeO, R = R = H, R =
1
3
2
4
1
2
3
1
2
3
6 4
Me (c); R = R = MeO, R = R = H (d); III, Ar = Ph (a), 4-MeC H (b); R = R = Me, R = H (c); R = MeO, R = H, R = Me (d);
2
1
3
R = R = MeO, R = H (e).
tions 1 and 4 of the side chain (H-bonded; broad band
two three-proton singlets from geminal methyl groups
in the pyrrolidine fragment (δ 1.30–1.65 ppm), a dou-
blet of doublets from two methylene protons in the
pyrrolidine ring (δ 2.16–2.46 ppm), singlets from 5-H
–
1
at 1595–1611 cm ).
1
Compounds IIIa–IIIe displayed in the H NMR
spectra (DMSO-d ) signals from aromatic substituents,
6
(δ 5.06–6.61 ppm), 2-H (δ 6.90–7.16 ppm), and NH
δ 10.75–10.83 ppm), and a broadened singlet from the
(
enolic hydroxy proton (δ 15.66–16.10 ppm), which
belong to major tautomer B. In addition, minor signals
assignable to diketone tautomer C were present; in
particular, protons of the CH group in the β-dicarbon-
2
yl fragment resonated as a singlet at δ 4.31–5.42 ppm,
and the 5-H and NH signals were located at δ 4.84–
6
.03 and 10.42–10.61 ppm, respectively. The B/C
tautomer ratio was estimated at ~5:1 from the signal
intensity ratio.
Figure shows the structure of molecule IIIe accord-
ing to the X-ray diffraction data. Compound IIIe
crystallized in centrosymmetric point symmetry group.
The spiro-fused cyclohexadiene and pyrrolidine rings
are planar within 0.04 Å, and they form a dihedral
angle of 89.4° with respect to each other. The bis-
Structure of the molecule of (2Z,5Z)-3-hydroxy-5-(6,9-di-
methoxy-3,3-dimethyl-8-oxo-2-azaspiro[4.5]deca-6,9-dien-
1
-ylidene)-1-phenylpent-2-ene-1,4-dione (IIIe) 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. 50 No. 12 2014

ACYLATION OF THE ENAMINO TAUTOMER OF 2-AZASPIRO[4.5]DECA-...
1781
enone fragment has s-cis-s-cis-s-cis configuration
fixed by intramolecular hydrogen bonds. The bond
lengths therein indicate rupture of conjugation at the
filtered off. Yield 82%, mp 194–195°C (decomp.; from
–
1
EtOH). IR spectrum, ν, cm : 3150 br (OH, NH), 1660
1
(C=Onaphth.), 1595 br (C=O, assoc.). H NMR spectrum
9
10
C –C bond whose length (1.505 Å) approaches that
typical of standard single bond. As a result, two
conjugated enone fragments can be distinguished in
the open-chain moiety with the C–C bond lengths in
each enone fragment ranging from 1.365 to 1.405 Å,
which is quite typical of such systems. Localization of
the OH proton and C–O bond lengths in the open-
(DMSO-d ), δ, ppm: B: 1.59 s and 1.65 s (3H each,
6
Me), 2.46 m (2H, 4′-H, AB), 5.08 s (1H, 5-H), 6.45 d
(1H, 3-H, naphth.), 6.92 s (1H, 2-H), 7.26 d (1H, 2-H,
naphth.), 7.41–8.06 m (9H, Harom), 10.77 s (1H, NH),
16.04 br.s (1H, OH); C: 1.53 s and 1.60 s (3H each,
Me), 2.41 m (2H, 4′-H, AB), 4.31 s (2H, 2-H), 4.85 s
(1H, 5-H), 6.43 d (1H, 3-H, naphth.), 7.22 d (1H, 2-H,
naphth.), 7.37–8.05 m (9H, Harom), 10.57 s (1H, NH).
Found, %: C 75.46; H 5.63; N 3.24. C H NO . Cal-
4
4
6
chain moiety confirm structure B. A short C –H ···O
contact [–x, –0.5 + y, 1.5 – z] was found in the crystal
packing of IIIe; the H···O distance is shorter by
26
23
4
culated, %: C 75.53; H 5.61; N 3.39.
Compounds IIIb–IIIe were synthesized in a similar
way.
2Z,5Z)-3-Hydroxy-5-(5′,5′-dimethyl-4-oxo-
~
0.3 Å than the sum of the corresponding van der
Waals radii (2.417 Å). Insofar as this contact may be
regarded as both forced and arising from specific
interaction C–H···O=C, its nature could be identified
only by quantum chemical calculations.
(
2
2
′H,4H-spiro[naphthalene-1,3′-pyrrolidin]-
′-ylidene)-1-(4-methylphenyl)pent-2-ene-1,4-dione
The mechanism of formation of compounds III is
(
IIIb). Yield 79%, mp 183–185°C (decomp.; from
likely to involve acylation of the =CH group in
–1
2
EtOH). IR spectrum, ν, cm : 3180 br (OH, NH), 1660
enamino tautomer A of spiro compound II by the
1
(C=Onaphth.), 1598 br (C=O, assoc.). H NMR spectrum
2
C =O carbonyl group of 5-arylfuran-2,3-dione I, fol-
(
DMSO-d ), δ, ppm: B: 1.59 s and 1.64 s (3H each,
6
1
2
lowed by cleavage of the furan ring at the O –C bond,
as described previously for the reactions of 5-aryl-
furan-2,3-diones with such heterocyclic enamines as
Me), 2.41 s (3H, MeC H ), 2.45 m (2H, 4′-H, AB),
6
4
5
.06 s (1H, 5-H), 6.44 d (1H, 3-H, naphth.), 6.90 s
(
(
1H, 2-H), 7.25 d (1H, 2-H, naphth.), 7.49–8.04 m
8H, Harom), 10.82 s (1H, NH), 16.10 br.s (1H, OH); C:
1
-methyl-3,4-dihydroisoquinolines [5] and Fischer
base [6]. Considerable steric hindrances created by
geminal methyl groups in the pyrrolidine fragment and
spiro-fused naphthalene ring in molecule IIa, as well
as by additional substituents in positions 3 and 6 of
molecules IIb and IIc, do not prevent them from
reacting with 5-arylfuran-2,3-diones.
1
2
5
.53 s and 1.58 s (3H each, Me), 2.39 s (3H, MeC H ),
.41 m (2H, 4′-H, AB), 4.33 s (2H, 2-H), 4.84 s (1H,
-H), 6.40 d (1H, 3-H, naphth.), 7.21 d (1H, 2-H,
6 4
naphth.), 7.43–8.00 m (8H, Harom), 10.52 s (1H, NH).
Found, %: C 75.69; H 5.95; N 3.17. C H NO . Cal-
27
25
4
culated, %: C 75.86; H 5.89; N 3.28.
2Z,5Z)-3-Hydroxy-5-(3,3,7,9-tetramethyl-8-oxo-
-azaspiro[4.5]deca-6,9-dien-1-ylidene)-1-phenyl-
pent-2-ene-1,4-dione (IIIc). Yield 75%, mp 173–
(
EXPERIMENTAL
2
The IR spectra were recorded in mineral oil on
a Bruker IFS 66v spectrometer with Fourier transform.
–
1
175°C (decomp.; from EtOAc). IR spectrum, ν, cm :
3243 br (OH, NH), 1662 (C =O), 1610 br (C=O,
assoc.). H NMR spectrum (DMSO-d
1
8
The H NMR spectra were measured on a Varian
1
Mercury-300BB (300 MHz) in DMSO-d or CDCl
6
), δ, ppm: B:
6
3
using hexamethyldisiloxane as internal reference. The
purity of the isolated compounds was checked by TLC
on Sorbfil plates (ethyl acetate–benzene, 1:5, or ethyl
acetate; development with a 0.5% solution of chloranil
in toluene).
1.30 s and 1.51 s (3H each, 3-Me), 2.11 s (6H, Me),
2.16 m (2H, 4-H, AB), 6.61 s (1H, 5-H), 6.67 s (1H,
6-H), 6.90 s (1H, 10-H), 7.16 s (1H, 2-H), 7.56–8.06 m
(5H, Ph), 10.78 s (1H, NH), 16.07 br.s (1H, OH); C:
1.23 s and 1.45 s (3H each, 3-Me), 2.09 s (6H, Me),
2
5
.15 m (2H, 4-H, AB), 5.38 s (2H, 2-H), 6.59 s (1H,
-H), 6.64 s (1H, 6-H), 6.85 s (1H, 10-H), 7.54–8.04 m
(
2Z,5Z)-3-Hydroxy-5-(5′,5′-dimethyl-4-oxo-
2
2
′H,4H-spiro[naphthalene-1,3′-pyrrolidin]-
′-ylidene)-1-phenylpent-2-ene-1,4-dione (IIIa).
(
5H, Ph), 10.57 s (1H, NH). Found, %: C 73.56;
H 6.52; N 3.57. C H NO . Calculated, %: C 73.64;
2
4
25
4
A solution of 1.0 mmol of 5-phenylfuran-2,3-dione
Ia) and 1.0 mmol of compound IIa in 20 mL of
H 6.44; N 3.58.
(
anhydrous benzene was heated for 4 h under reflux.
The mixture was cooled, and the precipitate was
(2Z,5Z)-3-Hydroxy-5-(9-methoxy-3,3,6-trimeth-
yl-8-oxo-2-azaspiro[4.5]deca-6,9-dien-1-ylidene)-1-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 12 2014

1
782
KONOVALOVA et al.
phenylpent-2-ene-1,4-dione (IIId). Yield 78%,
dependent thermal parameters, and the positions of the
NH and OH hydrogen atoms were refined indepen-
dently in isotropic approximation. A correction for
mp 132–134°C (decomp.; from EtOAc). IR spectrum,
–
1
8
ν, cm : 3261 br (OH, NH), 1664 (C =O), 1611 br
1
–1
(
C=O, assoc.). H NMR spectrum (DMSO-d ), δ, ppm:
absorption was applied empirically (μ = 0.092 mm ).
6
B: 1.56 s and 1.62 s (3H each, 3-Me), 1.97 s (3H, Me),
Final divergence factors: R = 0.0617, wR = 0.0887
1
2
2
5
2
1
3
.30 m (2H, 4-H, AB), 3.64 s (3H, OMe), 6.07 s (1H,
-H), 6.32 s (1H, CH), 6.59 s (1H, CH), 7.03 s (1H,
-H), 7.59–8.03 m (5H, Ph), 10.83 s (1H, NH),
6.09 br.s (1H, OH); C: 1.50 s and 1.60 s (3H each,
-Me), 1.94 s (3H, Me), 2.21 m (2H, 4-H, AB), 3.61 s
[for reflections with I > 2σ(I)] and R = 0.1947, wR =
0.1251 (for all reflections); goodness of fit S = 0.991.
1 2
The maximum and minimum electron density peaks
3
were 0.155 and –0.149 ē/Å , respectively. The set of
crystallographic data for compound IIIe was deposited
(
(
1
3H, OMe), 5.36 s (2H, 2-H), 6.03 s (1H, 5-H), 6.30 s
1H, CH), 6.58 s (1H, CH), 7.56–8.01 m (5H, Ph),
0.61 s (1H, NH). Found, %: C 70.62; H 6.20; N 3.31.
to the Cambridge Crystallographic Data Centre
(
entry no. CCDC 1 032 763) and is available at
www.ccdc.cam.ac.uk/data_request/cif.
C H NO . Calculated, %: C 70.74; H 6.18; N 3.44.
2
4
25
5
This study was performed under financial support
by the Russian Foundation for Basic Research (project
nos. 12-03-00146, 12-03-00696), by the Ministry of
Education and Science of the Russian Federation, and
by the Ministry of Education of Perm Krai (Interna-
tional Research Teams competition).
(
2Z,5Z)-3-Hydroxy-5-(6,9-dimethoxy-3,3-di-
methyl-8-oxo-2-azaspiro[4.5]deca-6,9-dien-
-ylidene)-1-phenylpent-2-ene-1,4-dione (IIIe).
Yield 80%, mp 183–184°C (decomp.; from EtOAc).
1
–
1
8
IR spectrum, ν, cm : 3207 br (OH, NH), 1661 (C =O),
1
1
604 br (C=O, assoc.). H NMR spectrum (CDCl ), δ,
3
ppm: B: 1.53 s and 1.55 s (3H each, 3-Me), 2.32 m (2H,
-H, AB), 3.69 s and 3.76 s (3H each, OMe), 5.73 s
REFERENCES
4
(
(
1
3
1H, 5-H), 7.05 s (1H, 2-H), 7.26 s (1H, CH), 7.36 s
1H, CH), 7.44–7.99 m (5H, Ph), 10.75 s (1H, NH),
5.66 br.s (1H, OH); C: 1.48 s and 1.50 s (3H each,
-Me), 2.29 m (2H, 4-H, AB), 3.64 s and 3.72 s (3H
1. Andreichikov, Yu.S., Gein, V.L., Zalesov, V.V., Kozlov,
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each, OMe), 5.42 s (2H, 2-H), 5.68 s (1H, 5-H), 7.21 s
1H, CH), 7.31 s (1H, CH), 7.42–7.96 m (5H, Ph),
0.42 s (1H, NH). Found, %: C 67.95; H 6.15; N 3.29.
C H NO . Calculated, %: C 68.07; H 5.95; N 3.31.
2
3
4
5
6
7
8
9
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(
1
2
4
25
6
X-Ray analysis of compound IIIe. The X-ray
diffraction data for compound IIIe were acquired on
an Xcalibur E automatic diffractometer equipped with
a CCD detector according to standard procedure
[
ω-scanning through a step of 1°; MoK irradiation,
α
λ 0.71073 Å; 295(2) K] [11]. The data were obtained
from a 0.25×0.20×0.15-mm fragment of a yellow pris-
matic single crystal. Monoclinic crystal system, space
group P2 /c; C H NO ; unit cell parameters: a =
1
9
cm . Total of 9774 reflection intensities were meas-
ured in the range –16 < h < 20, –15 < k < 16, –12 < l <
1
1
24 25
6
6.534(2), b = 13.514(2), c = 9.9331(12) Å; β =
3
6.761(13)°; V = 2204.1(6) Å ; Z = 4; d = 1.276 g×
calc
–
3
Ezhikova, M.A., and Kodess, M.I., Russ. J. Org. Chem.,
2
012, vol. 48, p. 69.
2; 4506 reflections were independent (R = 0.0791),
int
1
0. Glushkov, V.A., Stryapunina, O.G., Gorbunov, A.A.,
Maiorova, O.A., Slepukhin, P.A., Ryabukhina, S.Ya.,
Khorosheva, E.V., Sokol, V.I., and Shklyaev, Yu.V.,
Tetrahedron, 2010, vol. 66, p. 721.
and 1625 reflections were characterized by I > 2σ(I);
completeness 99.9% for the range 2.84 < Θ < 26.00.
The structure was solved using SHELXS-97 and was
2
refined using SHELXL-97 [12] against F in aniso-
11. CrysAlisPro, Version 1.171.36.32 (release 02-08-2013
tropic approximation for non-hydrogen atoms. The
positions of hydrogen atoms were refined according to
the riding model in isotropic approximation with
CrysAlis171.NET), Agilent Technologies.
12. Sheldrick, G.M., Acta Crystallogr., Sect. A, 2008,
vol. 64, p. 112.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 12 2014