Five-membered 2,3-dioxo heterocycles: C.* Reaction of methyl 1-aryl-3-cinnamoyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carbocylates with acyclic enamines

Article abstract of DOI:10.1134/S107042801403018X

Methyl 1-aryl-3-cinnamoyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carbocylates react with N-substituted ethyl 3-amino-3-phenylprop-2-enoates, ethyl 3-aminobut-2-enoates, 3-amino-1,3-diphenylprop-2-en-1-ones, and dimethyl 2-arylaminofumarates to give 9-ethoxyca

Full text of DOI:10.1134/S107042801403018X

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2014, Vol. 50, No. 3, pp. 406–411. © Pleiades Publishing, Ltd., 2014.
Original Russian Text © P.S. Silaichev, V.O. Filimonov, A.N. Maslivets, 2014, published in Zhurnal Organicheskoi Khimii, 2014, Vol. 50, No. 3,
pp. 416–420.
Five-Membered 2,3-Dioxo Heterocycles: C.* Reaction
of Methyl 1-Aryl-3-cinnamoyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-
2-carbocylates with Acyclic Enamines
P. S. Silaichev, V. O. Filimonov, and A. N. Maslivets
Perm State National Research University, ul. Bukireva 15, Perm, 614990 Russia
e-mail: koh2@psu.ru
Received January 16, 2013
Abstract—Methyl 1-aryl-3-cinnamoyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carbocylates react with N-substi-
tuted ethyl 3-amino-3-phenylprop-2-enoates, ethyl 3-aminobut-2-enoates, 3-amino-1,3-diphenylprop-2-en-
1-ones, and dimethyl 2-arylaminofumarates to give 9-ethoxycarbonyl-, 9-benzoyl-, and 8,9-bis(methoxycar-
bonyl)-4-cinnamoyl-1,7-diazaspiro[4.4]nona-3,8-dienes.
DOI: 10.1134/S107042801403018X
Nucleophilic heterocyclizations and recyclizations
of monocyclic 1H-pyrrole-2,3-diones by the action of
binucleophiles underlie convenient methods of synthe-
sis of various five-, six-, and seven-membered nitrogen
heterocycles and fused, bridged, and spiro heterocyclic
systems [2, 3]. We previously showed that methyl
3-acyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carbox-
ylates react with acyclic enamino ketones [4, 5] and
enamino esters [6] to give substituted 1,7-diazaspiro-
[4.4]nonanes as a result of nucleophilic attack on C2
and subsequent cyclization with participation of the
ester carbonyl carbon atom. Reactions of methyl
1-aryl-3-cinnamoyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-
2-carbocylates with enamines and enamino esters pos-
sessing functional groups in the α- and β-positions of
the enamino fragment were not reported previously.
In the present work we examined reactions of
methyl 1-aryl-3-cinnamoyl-4,5-dioxo-4,5-dihydro-1H-
pyrrole-2-carbocylates Ia–Id with acyclic enamines
IIa–IIc, IIIa, IIIb, and IVa–IVc. Compounds Ia and
Id were synthesized by reaction of methyl (2Z,5E)-
2-arylamino-4-oxo-6-phenylhexa-2,5-dienoates with
oxalyl chloride, and esters Ib and Ic were prepared as
described in [7].
1-ones IIIa and IIIb, and dimethyl 2-aminofumarates
IVa–IVc were carried out by heating equimolar
amounts of the reactants in boiling anhydrous toluene
or benzene (with compounds IVa–IVc) for 2–4 h (until
the bright red color typical of initial pyrrolediones dis-
appeared). As a result, we isolated in good yields the
corresponding substituted ethyl 4-cinnamoyl-1,7-di-
azaspiro[4.4]nona-3,8-diene-9-carboxylates Va–Vf,
9-benzoyl-4-cinnamoyl-8-phenyl-1,7-diazaspiro[4.4]-
nona-3,8-dienes VIa–VIc, and dimethyl 4-cinnamoyl-
1,7-diazaspiro[4.4]nona-3,8-diene-8,9-dicarboxylates
VIIa–VIIh.
Compounds Va–Vf, VIa–VIc, and VIIa–VIIh are
colorless or light yellow substances which melt at high
temperature with decomposition; they are readily
soluble in DMFA and DMSO, poorly soluble in
alcohols and haloalkanes, and insoluble in alkanes and
water. The presence of a enolic hydroxy group in their
molecules is confirmed by positive color test (cherry
color) with an alcoholic solution of FeCl3.
The IR spectra of Va–Vf, VIa–VIc, and VIIa–VIIh
contained absorption bands due to stretching vibrations
of the enolic OH group (3169–3458 cm–1), two lactam
carbonyl groups (1689–1755 cm–1), and ketone car-
bonyl group in the cinnamoyl fragment (1639–
1649 cm–1). In addition, compounds Va–Vf displayed
in the IR spectra ester carbonyl absorption band at
1671–1677 cm–1, compounds VIa–VIc showed ketone
carbonyl band at 1669–1672 cm–1 (benzoyl fragment);
The reactions of Ia–Id with N-substituted ethyl
3-amino-3-phenylprop-2-enoate IIa, ethyl 3-aminobut-
2-enoates IIb and IIc, 3-amino-1,3-diphenylprop-2-en-
* For communication XCIX, see [1].
406

FIVE-MEMBERED 2,3-DIOXO HETEROCYCLES: C.
407
Scheme 1.
Ph
O
Ph
O
O
Ph
OH
OH
O
O
R1
R2
MeOC(O)
NH
O
R1
H
+
O
N
N
O
–MeOH
R1
O
N
N
O
OEt
N
R2
EtO
Ar
Ar
R2
MeO
O
Ar
C(O)OEt
Ia–Ic
Ia–Ic
IIa–IIc
Va–Vf
Ph
O
Ph
R3
O
OH
OH
O
O
R3
MeOC(O)
NH
O
H
+
N
N
O
–MeOH
R3
N
N
Ph
Ph
Ar
Ar
Ph
Ph
Ph
O
C(O)Ph
IIIa, IIIb
VIa–VIc
Ph
O
Ph
O
OH
R4
O
OH
O
NH
O
MeOC(O)
R4
H
Ia–Id
+
MeO
N
N
O
–MeOH
R4
MeO
O
OMe
N
N
Ar
OMe
Ar
MeOC(O)
VIIa–VIIh
C(O)OMe
O
O
IVa–IVc
I, Ar = Ph (a), 4-MeC6H4 (b), 4-MeOC6H4 (c), 4-BrC6H4 (d); II, R1 = PhCH2, R2 = Ph (a), Me (b); R1 = Ph, R2 = Me (c);
III, R3 = PhCH2 (a), 4-MeC6H4 (b); IV, R4 = 4-MeC6H4 (a), 4-BrC6H4 (b), 4-ClC6H4 (c); V, Ar = Ph, R1 = PhCH2, R2 = Me (a);
Ar = 4-MeC6H4, R1 = PhCH2, R2 = Ph (b), Me (c); Ar = 4-MeOC6H4, R1 = PhCH2, R2 = Ph (d), Me (e); R1 = Ph, R2 = Me (f);
VI, Ar = Ph, R3 = PhCH2 (a); Ar = R3 = 4-MeC6H4 (b); Ar = 4-MeOC6H4, R3 = 4-MeC6H4 (c); VII, Ar = Ph, R4 = 4-MeC6H4 (a),
4-BrC6H4 (b), 4-ClC6H4 (c); Ar = 4-MeC6H4, R4 = 4-MeC6H4 (d), 4-ClC6H4 (e); Ar = 4-MeOC6H4, R4 = 4-MeC6H4 (f), 4-BrC6H4 (g);
Ar = R4 = 4-BrC6H4 (h).
Compounds Vb, VIc, and VIId displayed in the 13C
and diesters VIIa–VIIh gave rise to absorption in the
region 1670–1703 cm–1, corresponding to vibrations of
NMR spectra signals from carbon atoms in the exo-
two ester groups.
cyclic ethene fragment, aromatic rings and substituents
therein, ketone carbonyl group of the cinnamoyl sub-
stituent (δC 181.93–183.03 ppm), and lactam carbonyl
groups C2=O (δC 165.66–165.71 ppm) and C6=O
(δC 156.62–158.38 ppm). The spiro carbon atom reso-
nated at δC 69.58–70.88 ppm. In addition, signals from
the ethoxycarbonyl fragment in Vb (δC 13.37, 58.96,
160.91 ppm), benzoyl carbonyl carbon atom in VIc
(δC 190.86 ppm), and methoxycarbonyl fragments
in VIId (δC 51.94, 53.35, 160.10, 160.52 ppm) were
present.
1
In the H NMR spectra of Va–Vf, VIa–VIc, and
VIIa–VIIh we observed signals from protons in the
aromatic rings and substituents therein, two doublets at
δ 7.60–7.78 ppm from protons in the cinnamoyl
fragment with the coupling constant 3J = 15.4–16.4 Hz
typical of trans configuration of the double bond [8],
and a broadened singlet from the enolic hydroxy
proton at δ 12.23–13.35 ppm. In the spectra of Va–Vf,
protons in the ester ethoxy group resonated as a triplet
at δ 0.82–1.16 ppm (CH3) and a multiplet at δ 3.81–
4.07 ppm (CH2). The spectra of Va, Vc, Ve, and Vf
contained a singlet at δ 2.11–2.45 ppm from the 8-CH3
group, and singlets from the ester methoxy groups in
VIIa–VIIh were located at δ 3.60–3.66 ppm.
The spectral parameters of Va–Vf, VIa–VIc, and
VIIa–VIIh were very similar to those found for
4-methyl 9-ethyl 7-benzyl-3-hydroxy-1-(4-methoxy-
phenyl)-8-methyl-2,6-dioxo-1,7-diazaspiro[4.4]nona-
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SILAICHEV et al.
408
3,8-diene-4,9-dicarboxylate [9] whose structure was
unambiguously determined by X-ray analysis.
Compound Id was synthesized in a similar way.
Methyl 1-(4-bromophenyl)-3-cinnamoyl-4,5-
dioxo-4,5-dihydro-1H-pyrrole-2-carboxylate (Id).
Yield 82%, mp 207–208°C (from benzene–hexane,
1:1). IR spectrum, ν, cm–1: 1783 (C5=O), 1736 (C=O,
Presumably, compounds Va–Vf, VIa–VIc, and
VIIa–VIIh are formed via initial addition of the
activated β-CH group of the enamine fragment in IІ–
IV to C2 of pyrrole І, followed by Z/E isomerization of
the enamine fragment and closure of new pyrrole ring
as a result of attack by the secondary amino group on
the ester carbonyl carbon atom, by analogy with the
scheme proposed previously [6].
1
ester), 1679 (C4=O), 1658 (3-C=O). H NMR spec-
trum, δ, ppm: 3.60 s (3H, OMe), 7.31–7.86 m (11H,
H
arom, CH=CH). Found, %: C 57.31; H 3.25; N 3.16.
C21H14BrNO5. Calculated, %: C 57.29; H 3.21; N 3.18.
Ethyl 7-benzyl-4-cinnamoyl-3-hydroxy-8-meth-
yl-2,6-dioxo-1-phenyl-1,7-diazaspiro[4.4]nona-3,8-
diene-9-carboxylate (Va). A solution of 1.0 mmol of
enamine IIb in 5 mL of anhydrous toluene was added
to a solution of 1.0 mmol of compound Ia in 20 mL of
anhydrous toluene. The mixture was heated for 2 h
under reflux and cooled, and the precipitate was
filtered off and recrystallized from toluene. Yield 70%,
mp 197–198°C. IR spectrum, ν, cm–1: 3428 (OH),
1726 (C6=O), 1696 (C2=O), 1673 (9-C=O), 1638
EXPERIMENTAL
The IR spectra were recorded on a Perkin Elmer
Spectrum Two spectrometer from samples dispersed in
1
mineral oil. The H and 13C NMR spectra were
measured on a Bruker AM-400 instrument at 400 and
100 MHz, respectively, from solutions in DMSO-d6
using tetramethylsilane as internal reference. The
purity of the isolated compounds was checked by ultra-
HPLC (Acquity UPLC BEH C18 column, grain size
1.7 μm; eluent aqueous methanol or aqueous aceto-
nitrile, flow rate 0.3–0.5 mL/s; ESI MS Xevo TQD
detector).
1
(4-C=O). H NMR spectrum, δ, ppm: 1.13 t (3H,
CH3CH2, J = 7.0 Hz), 2.25 s (3H, Me), 4.04 m (2H,
OCH2), 4.76 d and 4.91 d (1H each, CH2Ph, J =
16.4 Hz), 6.94–7.69 m (15H, Ph), 7.62 d (1H,
C O C H = C H P h , J = 1 6 . 0 H z ) , 7 . 7 3 d ( 1 H,
COCH=CHPh, J = 16.0 Hz), 13.36 br.s (1H, OH).
Found, %: C 72.19; H 5.12; N 5.10. C33H28N2O6. Cal-
culated, %: C 72.25; H 5.14; N 5.11.
Methyl 3-cinnamoyl-4,5-dioxo-1-phenyl-4,5-
dihydro-1H-pyrrole-2-carboxylate (Ia). Aniline,
0.1 mol, and acetic acid, 2 mL, were added to
a solution of 0.1 mol of methyl (2Z,5E)-2-hydroxy-4-
oxo-6-phenylhexa-2,5-dienoate in 200 mL of toluene,
and the mixture was heated for 5 h under reflux in
a flask equipped with a Dean–Stark trap (until water
no longer separated). The solvent was removed under
reduced pressure, and the residue was passed through
a column charged with silica gel (Silicagel L, 100–
400 μm) using toluene–isooctane (1:1) as eluent. The
first bright red fraction was collected. Removal of the
solvent gave oily methyl 4-oxo-2-(4-phenylamino)-6-
phenylhexa-2,5-dienoate which was used without addi-
tional purification.
Compounds Vb–Vf were synthesized in a similar
way.
Ethyl 7-benzyl-4-cinnamoyl-3-hydroxy-1-
(4-methylphenyl)-2,6-dioxo-8-phenyl-1,7-diaza-
spiro[4.4]nona-3,8-diene-9-carboxylate (Vb). Yield
68%, mp 209–210°C. IR spectrum, ν, cm–1: 3417
(OH), 1723 (C6=O), 1698 (C2=O), 1671 (9-C=O),
1644 (4-C=O). 1H NMR spectrum, δ, ppm: 0.83 t (3H,
CH3CH2, J = 7.1 Hz), 2.41 s (3H, Me), 3.81 m (2H,
OCH2), 4.27 d and 4.69 d (1H each, CH2Ph, J =
15.9 Hz), 6.52–7.71 m (19H, Harom), 7.70 d (1H,
C O C H = C H P h , J = 1 5 . 5 H z ) , 7 . 7 8 d ( 1 H,
COCH=CHPh, J = 15.5 Hz), 13.24 br.s (1H, OH).
13C NMR spectrum, δC, ppm: 13.37 (CH2CH3), 20.64
(Me), 43.85 (CH2Ph), 58.96 (OCH2), 70.21 (C5),
105.09 (C9), 117.88 (C4), 123.92–138.22 (Carom, C8),
142.14 (COCH=CHPh), 158.38 (C6), 160.91 (9-C=O),
165.71 (C2), 173.73 (C3), 183.03 (4-C=O). Found, %:
C 74.93; H 5.17; N 4.46. C39H32N2O6. Calculated, %:
C 74.99; H 5.16; N 4.48.
The product, 0.05 mol, was dissolved in 30 mL of
anhydrous benzene, 0.05 mol of oxalyl chloride was
added, the mixture was heated for 70 min under reflux,
30 mL of anhydrous hexane was added, the mixture
was cooled, and the precipitate was filtered off and
recrystallized. Yield 86%, mp 188–189°C (from
benzene–hexane, 1 :1). IR spectrum, ν, cm–1: 1784
(C5=O), 1736 (C=O, ester), 1717 (C4=O), 1659
1
(3-C=O). H NMR spectrum, δ, ppm: 3.59 s (3H,
OMe), 7.15–7.79 m (12H, Harom, CH=CH). Found, %:
C 69.76; H 4.16; N 3.82. C21H15NO5. Calculated, %:
C 69.80; H 4.18; N 3.88.
Ethyl 7-benzyl-4-cinnamoyl-3-hydroxy-8-meth-
yl-1-(4-methylphenyl)-2,6-dioxo-1,7-diazaspiro[4.4]-
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FIVE-MEMBERED 2,3-DIOXO HETEROCYCLES: C.
409
nona-3,8-diene-9-carboxylate (Vc). Yield 71%,
mp 236–238°C. IR spectrum, ν, cm–1: 3170 (OH),
1725 (C6=O), 1696 (C2=O), 1675 (9-C=O), 1647
9-Benzoyl-7-benzyl-4-cinnamoyl-3-hydroxy-1,8-
diphenyl-1,7-diazaspiro[4.4]nona-3,8-diene-2,6-di-
one (VIa). Enamine IIIa, 1.0 mmol, was added to
a solution of 1.0 mmol of compound Ia in 15 mL of
anhydrous toluene, the mixture was heated for 3 h
under reflux and cooled, and the precipitate was
filtered off and recrystallized from ethyl acetate–di-
chloroethane. Yield 78%, mp 274–275°C. IR spectrum,
ν, cm–1: 3180 (OH), 1722 (C6=O), 1713 (C2=O), 1672
1
(4-C=O). H NMR spectrum, δ, ppm: 1.12 t (3H,
CH3CH2, J = 7.0 Hz), 2.24 s (3H, Me), 2.35 s (3H,
8-Me), 4.04 m (2H, OCH2), 4.75 d and 4.90 d (1H
each, CH2Ph, J = 16.8 Hz), 6.87–7.68 m (14H, Harom),
7.60 d (1H, COCH=CHPh, J = 16.1 Hz), 7.77 d (1H,
COCH=CHPh, J = 16.1 Hz), 13.33 br.s (1H, OH).
Found, %: C 72.53; H 5.34; N 4.99. C34H30N2O6. Cal-
culated, %: C 72.58; H 5.37; N 4.98.
1
(9-C=O), 1642 (4-C=O). H NMR spectrum, δ, ppm:
4.54 d and 4.73 d (1H, CH2Ph, J = 16.4 Hz), 6.65–
7.71 m (25H, Ph), 7.71 d (1H, COCH=CHPh, J =
15.9 Hz), 7.78 d (1H, COCH=CHPh, J = 15.9 Hz),
13.13 br.s (1H, OH). Found, %: C 78.43; H 4.67;
N 4.38. C42H30N2O5. Calculated, %: C 78.49; H 4.70;
N 4.36.
Ethyl 7-benzyl-4-cinnamoyl-3-hydroxy-1-(4-me-
thoxyphenyl)-2,6-dioxo-8-phenyl-1,7-diazaspiro-
[4.4]nona-3,8-diene-9-carboxylate (Vd). Yield 75%,
mp 199–200°C. IR spectrum, ν, cm–1: 3431 (OH),
1723 (C6=O), 1690 (C2=O), 1677 (9-C=O), 1649
1
Compounds VIb and VIc were synthesized in
a similar way.
(4-C=O). H NMR spectrum, δ, ppm: 0.82 t (3H,
CH3CH2, J = 7.0 Hz), 3.82 m (2H, OCH2), 3.84 s (3H,
OMe), 4.25 d and 4.70 d (1H each, CH2Ph, J =
16.5 Hz), 6.49–7.71 m (19H, Harom), 7.69 d (1H,
C O C H = C H P h , J = 1 6 . 0 H z ) , 7 . 7 7 d ( 1 H,
COCH=CHPh, J = 16.0 Hz), 13.30 br.s (1H, OH).
Found, %: C 73.15; H 5.00; N 4.32. C39H32N2O7. Cal-
culated, %: C 73.11; H 5.03; N 4.37.
9-Benzoyl-4-cinnamoyl-3-hydroxy-1,7-bis-
(4-methylphenyl)-8-phenyl-1,7-diazaspiro[4.4]nona-
3,8-diene-2,6-dione (VIb). Yield 82%, mp 281–
283°C. IR spectrum, ν, cm–1: 3178 (OH), 1728 (C6=O),
1
1689 (C2=O), 1669 (9-C=O), 1647 (4-C=O). H NMR
spectrum, δ, ppm: 2.24 s and 2.35 s (3H each, Me),
6.70–7.72 m (23H, Harom), 7.73 d (1H, COCH=CHPh,
J = 16.0 Hz), 7.78 d (1H, COCH=CHPh, J = 16.0 Hz),
13.05 br.s (1H, OH). Found, %: C 78.67; H 4.89;
N 4.23. C43H32N2O5. Calculated, %: C 78.64; H 4.91;
N 4.27.
Ethyl 7-benzyl-4-cinnamoyl-3-hydroxy-1-(4-me-
thoxyphenyl)-8-methyl-2,6-dioxo-1,7-diazaspiro-
[4.4]nona-3,8-diene-9-carboxylate (Ve). Yield 69%,
mp 235–236°C. IR spectrum, ν, cm–1: 3458 (OH),
1721 (C6=O), 1696 (C2=O), 1671 (9-C=O), 1644
1
(4-C=O). H NMR spectrum, δ, ppm: 1.13 t (3H,
9-Benzoyl-4-cinnamoyl-3-hydroxy-1-(4-methoxy-
phenyl)-7-(4-methylphenyl)-8-phenyl-1,7-diaza-
spiro[4.4]nona-3,8-diene-2,6-dione (VIc). Yield 79%,
mp 277–278°C. IR spectrum, ν, cm–1: 3205 (OH),
1731 (C6=O), 1695 (C2=O), 1671 (9-C=O), 1646
(4-C=O). 1H NMR spectrum, δ, ppm: 2.24 s (3H, Me),
3.78 s (3H, OMe), 6.70–7.74 m (23H, Harom), 7.73 d
(1H, COCH=CHPh, J = 15.4 Hz), 7.73 d (1H,
COCH=CHPh, J = 15.4 Hz), 13.05 br.s (1H, OH).
13C NMR spectrum, δC, ppm: 20.50 (Me), 55.44
CH3CH2, J = 7.0 Hz), 2.45 s (3H, Me), 3.80 s (3H,
OMe), 4.06 m (2H, OCH2), 4.73 d and 4.90 d (1H
each, CH2Ph, J = 16.5 Hz), 6.89–7.68 m (14H, Harom),
7.60 d (1H, COCH=CHPh, J = 16.2 Hz), 7.72 d (1H,
COCH=CHPh, J = 16.2 Hz), 13.32 br.s (1H, OH).
Found, %: C 70.54; H 5.26; N 4.81. C34H30N2O7. Cal-
culated, %: C 70.58; H 5.23; N 4.84.
Ethyl 4-cinnamoyl-3-hydroxy-1-(4-methoxyphe-
nyl)-8-methyl-2,6-dioxo-7-phenyl-1,7-diazaspiro-
[4.4]nona-3,8-diene-9-carboxylate (Vf). Yield 73%,
mp 236–237°C. IR spectrum, ν, cm–1: 3169 (OH),
1727 (C6=O), 1703 (C2=O), 1674 (9-C=O), 1645
(OMe), 71.88 (C5), 113.27 (C9), 114.56–138.16 (Carom
,
C4, C8), 142.23 (COCH=CHPh), 157.22 (C6), 159.11
(COMe), 165.66 (C2), 173.99 (C3), 182.62 (4-C=O),
190.86 (COPh). Found, %: C 76.84; H 4.74; N 4.14.
C43H32N2O6. Calculated, %: C 76.77; H 4.79; N 4.16.
1
(4-C=O). H NMR spectrum, δ, ppm: 1.16 t (3H,
CH3CH2, J = 7.0 Hz), 2.11 s (3H, Me), 3.80 s (3H,
OMe), 4.07 m (2H, OCH2), 7.06–7.71 m (14H, Harom),
7.67 d (1H, COCH=CHPh, J = 15.7 Hz), 7.74 d (1H,
COCH=CHPh, J = 15.7 Hz), 13.35 br.s (1H, OH).
Found, %: C 70.16; H 5.03; N 4.93. C33H28N2O7. Cal-
culated, %: C 70.20; H 5.00; N 4.96.
Dimethyl 4-cinnamoyl-3-hydroxy-7-(4-methyl-
phenyl)-2,6-dioxo-1-phenyl-1,7-diazaspiro[4.4]-
nona-3,8-diene-8,9-dicarboxylate (VIIa). Enamine
IVa, 1.0 mmol, was added to a solution of 1.0 mmol of
compound Іa in 20 mL of anhydrous benzene, the
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SILAICHEV et al.
410
mixture was heated for 3–4 h under reflux and cooled,
and the precipitate was filtered off and recrystallized
from ethyl acetate. Yield 82%, mp 262–264°C. IR
spectrum, ν, cm–1: 3331 (OH), 1755 (C6=O), 1728
(C2=O), 1703 (8-C=O), 1674 (9-C=O), 1647 (4-C=O).
1H NMR spectrum, δ, ppm: 2.35 s (3H, Me), 3.60 s
and 3.62 s (3H each, COOMe), 7.06–7.73 m (14H,
Harom), 7.70 d (1H, COCH=CHPh, J = 16.0 Hz), 7.75 d
(1H, COCH=CHPh, J = 16.0 Hz), 12.24 br.s (1H, OH).
Found, %: C 68.52; H 4.55; N 4.90. C33H26N2O8. Cal-
culated, %: C 68.51; H 4.53; N 4.84.
(8-C=O), 160.52 (9-C=O), 165.69 (C2), 172.97 (C3),
181.93 (4-C=O). Found, %: C 68.93; H 4.71; N 4.70.
C34H28N2O8. Calculated, %: C 68.91; H 4.76; N 4.73.
Dimethyl 7-(4-chlorophenyl)-4-cinnamoyl-3-hy-
droxy-1-(4-methylphenyl)-2,6-dioxo-1,7-diazaspiro-
[4.4]nona-3,8-diene-8,9-dicarboxylate (VIIe). Yield
78%, mp 249–250°C. IR spectrum, ν, cm–1: 3286
(OH), 1768 (C6=O), 1724 (C2=O), 1688 (8-C=O),
1
1670 (9-C=O), 1639 (4-C=O). H NMR spectrum, δ,
ppm: 2.35 s (3H, Me), 3.63 s and 3.65 s (3H each,
COOMe), 7.00–7.80 m (13H, Harom), 7.69 d (1H,
C O C H = C H P h , J = 1 6 . 0 H z ) , 7 . 7 5 d ( 1 H,
COCH=CHPh, J = 16.0 Hz), 12.28 br.s (1H, OH).
Found, %: C 64.69; H 4.08; N 4.58. C33H25ClN2O8.
Calculated, %: C 64.66; H 4.11; N 4.57.
Compounds VIIb–VIIh were synthesized in
a similar way.
Dimethyl 7-(4-bromophenyl)-4-cinnamoyl-3-hy-
droxy-2,6-dioxo-1-phenyl-1,7-diazaspiro[4.4]nona-
3,8-diene-8,9-dicarboxylate (VIIb). Yield 79%,
mp 264–265°C. IR spectrum, ν, cm–1: 3285 (OH),
1767 (C6=O), 1725 (C2=O), 1689 (8-C=O), 1670
Dimethyl 4-cinnamoyl-3-hydroxy-1-(4-methoxy-
phenyl)-7-(4-methylphenyl)-2,6-dioxo-1,7-diaza-
spiro[4.4]nona-3,8-diene-8,9-dicarboxylate (VIIf).
Yield 81%, mp 247–249°C. IR spectrum, ν, cm–1: 3264
(OH), 1767 (C6=O), 1732 (C2=O), 1698 (8-C=O),
1
(9-C=O), 1645 (4-C=O). H NMR spectrum, δ, ppm:
3.65 s and 3.66 s (3H each, COOMe), 7.15–7.80 m
(14H, Harom), 7.69 d (1H, COCH=CHPh, J = 15.8 Hz),
7.75 d (1H, COCH=CHPh, J = 15.8 Hz), 12.30 br.s
(1H, OH). Found, %: C 59.69; H 3.64; N 4.38.
C32H23BrN2O8. Calculated, %: C 59.73; H 3.60; N 4.35.
1
1674 (9-C=O), 1644 (4-C=O). H NMR spectrum, δ,
ppm: 2.35 s (3H, Me), 3.62 s and 3.64 s (3H each,
COOMe), 3.80 s (3H, OMe), 7.02–7.72 m (13H,
H
arom), 7.70 d (1H, COCH=CHPh, J = 16.0 Hz), 7.75 d
(1H, COCH=CHPh, J = 16.0 Hz), 12.30 br.s (1H, OH).
Found, %: C 67.07; H 4.60; N 4.65. C34H28N2O9.
Calculated, %: C 67.10; H 4.64; N 4.60.
Dimethyl 7-(4-chlorophenyl)-4-cinnamoyl-3-hy-
droxy-2,6-dioxo-1-phenyl-1,7-diazaspiro[4.4]nona-
3,8-diene-8,9-dicarboxylate (VIIc). Yield 80%,
mp 271–273°C. IR spectrum, ν, cm–1: 3287 (OH),
1767 (C6=O), 1726 (C2=O), 1690 (8-C=O), 1671
Dimethyl 7-(4-bromophenyl)-4-cinnamoyl-3-hy-
droxy-1-(4-methoxyphenyl)-2,6-dioxo-1,7-diaza-
spiro[4.4]nona-3,8-diene-8,9-dicarboxylate (VIIg).
Yield 78%, mp 249–250°C. IR spectrum, ν, cm–1: 3280
(OH), 1767 (C6=O), 1731 (C2=O), 1698 (8-C=O),
1
(9-C=O), 1645 (4-C=O). H NMR spectrum, δ, ppm:
3.63 s and 3.64 s (3H each, COOMe), 7.12–7.79 m
(14H, Harom), 7.69 d (1H, COCH=CHPh, J = 15.9 Hz),
7.75 d (1H, COCH=CHPh, J = 16.0 Hz), 12.26 br.s
(1H, OH). Found, %: C 64.13; H 3.91; N 4.64.
C32H23ClN2O8. Calculated, %: C 64.17; H 3.87; N 4.68.
1
1676 (9-C=O), 1645 (4-C=O). H NMR spectrum, δ,
ppm: 3.65 s and 3.66 s (3H each, COOMe), 3.80 s
(3H, OMe), 7.02–7.79 m (13H, Harom), 7.69 d (1H,
C O C H = C H P h , J = 1 5 . 8 H z ) , 7 . 7 5 d ( 1 H,
COCH=CHPh, J = 15.8 Hz), 12.23 br.s (1H, OH).
Found, %: C 58.88; H 3.69; N 4.17. C33H25BrN2O9.
Calculated, %: C 58.85; H 3.74; N 4.16.
Dimethyl 4-cinnamoyl-3-hydroxy-1,7-bis-
(4-methylphenyl)-2,6-dioxo-1,7-diazaspiro[4.4]-
nona-3,8-diene-8,9-dicarboxylate (VIId). Yield 83%,
mp 251–252°C. IR spectrum, ν, cm–1: 3291 (OH),
1759 (C6=O), 1727 (C2=O), 1698 (8-C=O), 1674
Dimethyl 1,7-bis(4-bromophenyl)-4-cinnamoyl-
3-hydroxy-2,6-dioxo-1,7-diazaspiro[4.4]nona-3,8-
diene-8,9-dicarboxylate (VIIh). Yield 79%, mp 270–
271°C. IR spectrum, ν, cm–1: 3271 (OH), 1764 (C6=O),
1734 (C2=O), 1699 (8-C=O), 1679 (9-C=O), 1644
(4-C=O). 1H NMR spectrum, δ, ppm: 3.62 s and 3.66 s
(3H, COOMe), 7.06–7.86 m (13H, Harom), 7.68 d
(1H, COCH=CHPh, J = 15.8 Hz), 7.75 d (1H,
COCH=CHPh, J = 15.8 Hz), 12.34 br.s (1H, OH).
Found, %: C 53.23; H 3.04; N 3.85. C32H22Br2N2O8.
Calculated, %: C 53.21; H 3.07; N 3.88.
1
(9-C=O), 1644 (4-C=O). H NMR spectrum, δ, ppm:
2.35 s and 2.36 s (3H each, Me), 3.61 s and 3.62 s
(3H each, COOMe), 7.00–7.72 m (13H, Harom), 7.71 d
(1H, COCH=CHPh, J = 15.9 Hz), 7.75 d (1H,
COCH=CHPh, J = 15.9 Hz), 12.31 br.s (1H, OH).
13C NMR spectrum, δC, ppm: 20.70 and 20.72 (Me),
51.94 and 53.35 (OCH3), 69.58 (C5), 104.92 (C9),
117.52 (C4), 123.59–139.13 (Carom), 142.78
(COCH=CHPh), 149.36 (C8), 156.62 (C6), 160.10
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 3 2014

FIVE-MEMBERED 2,3-DIOXO HETEROCYCLES: C.
411
4. Silaichev, P.S., Filimonov, V.O., Slepukhin, P.A., and
Maslivets, A.N., Russ. J. Org. Chem., 2012, vol. 48,
p. 1329.
5. Bannikova, Yu.N., Khalturina, V.V., Sedegova, E.A., and
Maslivets, A.N., Russ. J. Org. Chem., 2007, vol. 43,
p. 154.
6. Bannikova, Yu.N., Sedegova, E.A., Khalturina, V.V., and
Maslivets, A.N., Russ. J. Org. Chem., 2007, vol. 43,
p. 1338.
7. Silaichev, P.S., Filimonov, V.O., Slepukhin, P.A., and
Maslivets, A.N., Russ. J. Org. Chem., 2012, vol. 48,
p. 561.
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 Competi-
tion), and by the Russian Foundation for Basic
Research (project nos. 12-03-00696, 12-03-31157, 13-
03-96009).
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 3 2014