Five-membered 2,3-dioxo heterocycles: CIII. Spiro heterocyclization of 4,5-diaroyl-1H-pyrrole-2,3-diones with 3-aminobut-2-enenitrile

Article abstract of DOI:10.1134/S1070428014060153

1-Aryl-4,5-diaroyl-1H-pyrrole-2,3-diones reacted with 3-aminobut-2- enenitrile to produce 1,6-diaryl-4-aroyl-3-hydroxy-8-methyl-2-oxo-1,7- diazaspiro[4.4]nona-3,6,8-triene-9-carbonitriles.

Full text of DOI:10.1134/S1070428014060153

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2014, Vol. 50, No. 6, pp. 843–845. © Pleiades Publishing, Ltd., 2014.
Original Russian Text © P.S. Silaichev, Yu.G. Stepanyan, N.V. Kudrevatykh, A.N. Maslivets, 2014, published in Zhurnal Organicheskoi Khimii, 2014, Vol. 50,
No. 6, pp. 860–862.
Five-Membered 2,3-Dioxo Heterocycles:
CIII.* Spiro Heterocyclization of 4,5-Diaroyl-1H-pyrrole-
2,3-diones with 3-Aminobut-2-enenitrile
P. S. Silaichev, Yu. G. Stepanyan, N. V. Kudrevatykh, and A. N. Maslivets
Perm State National Research University, ul. Bukireva 15, Perm 614990 Russia
e-mail: koh2@psu.ru
Received March 27, 2013
Abstract—1-Aryl-4,5-diaroyl-1H-pyrrole-2,3-diones reacted with 3-aminobut-2-enenitrile to produce 1,6-di-
aryl-4-aroyl-3-hydroxy-8-methyl-2-oxo-1,7-diazaspiro[4.4]nona-3,6,8-triene-9-carbonitriles.
DOI: 10.1134/S1070428014060153
Nucleophilic spiro heterocyclizations and recycliza-
tions of monocyclic 1H-pyrrole-2,3-diones by the
action of binucleophiles provide a convenient synthetic
route to various five-, six-, and seven-membered aza
heterocycles and fused, bridged, and spiro heterocyclic
systems [2, 3]. We previously found that reactions of
4,5-diaroyl-1H-pyrrole-2,3-diones with ethyl 3-amino-
3-phenylprop-2-enoate lead to the formation of substi-
tuted ethyl 1,7-diazaspiro[4.4]nona-3,6,8-triene-9-car-
boxylates via addition of nucleophilic enamine centers
(β-CH group of the enamine fragment and amino
group) to C5 in the pyrrole ring and 5-aroyl carbonyl
carbon atom and subsequent elimination of water [4].
In order to develop a procedure for the synthesis of
1,7-diazaspiro[4.4]nona-3,6,8-triene-9-carbonitriles, in
the present work we examined reactions of the same
4,5-diaroyl-1H-pyrrole-2,3-diones with 3-aminobut-2-
enenitrile.
By heating equimolar amounts of 1-aryl-4,5-di-
aroyl-1H-pyrrole-2,3-diones [5] Ia–If and 3-aminobut-
2-enenitrile (II) [6] in boiling anhydrous benzene for
2–3 h (TLC monitoring) we obtained the correspond-
ing 4-aroyl-1,6-diaryl-3-hydroxy-8-methyl-2-oxo-1,7-
diazaspiro[4.4]nona-3,6,8-triene-9-carbonintriles IIIa–
IIIf in good yields (Scheme 1). Compounds IIIa–IIIf
were isolated as light yellow high-melting crystalline
substances which were readily soluble in alcohols and
chlorinated hydrocarbons and insoluble in alkanes and
water. They showed a positive color test (cherry color)
for enolic hydroxy group on treatment with an alco-
holic solution of iron(III) chloride.
The IR spectra of IIIa–IIIf contained absorption
bands typical of stretching vibrations of enolic hy-
droxy group (broad band at 3158–3192 cm–1), cyano
group (2205–2211 cm–1), and lactam (C2=O, 1689–
1703 cm–1) and ketone carbonyl groups (1660–
Scheme 1.
O
O
Ar2
Ar2
O
Ar2
Ar2
OH
Ar2
Ar2
OH
O
H2N
CN
4
6
3
7N
+
5
2
O
–H2O
1
N
N
O
Me
O
8
O
N
H2N
9
Ar1
Ar1
O
Me
Ar1
CN
CN
Me
Ia–If
II
A
IIIa–IIIf
Ar1 = Ph, Ar2 = 2,5-Me2C6H3 (a); Ar1 = 4-MeC6H4, Ar2 = Ph (b), 4-MeC6H4 (c), 2,5-Me2C6H3 (d);
Ar1 = 4-MeOC6H4, Ar2 = Ph (e), 4-MeC6H4 (f).
* For communication CII, see [1].
843

SILAICHEV et al.
844
1669 cm–1). Compounds IIIa–IIIf displayed in the
1H NMR spectra signals from protons in the aromatic
rings and substituents therein, a three-proton singlet
from the 8-Me group at δ 2.24–2.26 ppm, and a broad-
ened singlet from the enolic hydroxy proton at δ 11.47–
12.45 ppm. In the 13C NMR spectrum of IIIa we
observed signals from carbon atoms in aromatic and
aliphatic substituents, C3=C4 and C8=C9 ethylene frag-
ments, aroyl carbonyl group (δC 186.98 ppm), lactam
carbonyl group (δC 165.01 ppm), nitrile group
(δC 113.54 ppm), and C6 (δC 168.80 ppm) and a signal
at δC 81.16 ppm belonging to the spiro carbon atom.
The positions of signals in the 13C NMR spectrum of
IIIa were very similar to those found for ethyl 4-ben-
zoyl-3-hydroxy-1-(4-methylphenyl)-2-oxo-6,8-diphe-
nyl-1,7-diazaspiro[4.4]nona-3,6,8-triene-9-carboxylate
whose structure was determined by X-ray analysis [4].
monitored by UPLC. When the reaction was complete,
the mixture was evaporated by half, the residue was
diluted with an equal volume of petroleum ether
(bp 40–70°C) and cooled, and the precipitate was
filtered off and recrystallized from toluene. Yield 74%,
mp 201–202°C. IR spectrum, ν, cm–1: 3158 (OH),
1
2211 (CN), 1700 (C2=O), 1669 (4-C=O). H NMR
spectrum, δ, ppm: 2.02 s (3H, CH3), 2.24 s (3H, CH3),
2.25 s (3H, CH3), 2.27 s (3H, CH3), 2.34 s (3H, CH3),
6.87–7.44 m (11H, Harom), 12.45 br.s (1H, OH).
13C NMR spectrum, δC, ppm: 16.93 (Me), 20.49 (Me),
21.08 (Me), 21.18 (Me), 81.16 (C5), 103.20 (C9),
113.54 (CN), 114.07 (C4), 125.68–143.75, 152.97 (C8),
165.01 (C2), 168.80 (C6), 177.73 (C3), 186.99 (4-CO).
Found, %: C 76.57; H 5.45; N 8.44. C32H27N3O3. Cal-
culated, %: C 76.63; H 5.43; N 8.38.
Compounds IIIb–IIIf were synthesized in a similar
way.
Presumably, the described reaction involves initial
addition of the β-CH group in the enamine fragment of
II to C5 of pyrroledione I and subsequent intramolec-
ular cyclization via nucleophilic attack by the primary
amino group in intermediate A on the aroyl carbonyl
carbon atom attached to C5 of the pyrrole ring and
elimination of water (Scheme 1). This reaction may be
regarded as one more example of direct spiro hetero-
cyclization of 4,5-diaroyl-1H-pyrrole-2,3-diones by the
action of acyclic enamines, and it provides a synthetic
route to new functional derivatives of the difficultly
accessible 1,7-diazaspiro[4.4]nona-3,6,8-triene system.
4-Benzoyl-3-hydroxy-8-methyl-1-(4-methylphe-
nyl)-2-oxo-6-phenyl-1,7-diazaspiro[4.4]nona-3,6,8-
triene-9-carbonitrile (IIIb). Yield 77%, mp 152–
153°C. IR spectrum, ν, cm–1: 3192 (OH), 2205 (CN),
1694 (C2=O), 1665 (4-C=O). H NMR spectrum, δ,
1
ppm: 2.25 s (3H, CH3), 2.30 s (3H, CH3), 6.80–7.92 m
(14H, Harom), 11.47 br.s (1H, OH). Found, %: C 75.84;
H 4.57; N 9.11. C29H21N3O3. Calculated, %: C 75.80;
H 4.61; N 9.14.
3-Hydroxy-8-methyl-4-(4-methylbenzoyl)-1,6-
bis(4-methylphenyl)-2-oxo-1,7-diazaspiro[4.4]nona-
3,6,8-triene-9-carbonitrile (IIIc). Yield 72%,
mp 145–146°C. IR spectrum, ν, cm–1: 3163 (OH),
EXPERIMENTAL
2209 (CN), 1701 (C2=O), 1667 (4-C=O). H NMR
1
The IR spectra were recorded on a Perkin Elmer
Spectrum Two spectrometer from samples dispersed in
spectrum, δ, ppm: 2.25 s (3H, CH3), 2.26 s (3H, CH3),
2.36 s (6H, CH3), 6.81–7.82 m (12H, Harom), 12.06 br.s
(1H, OH). Found, %: C 76.41; H 5.14; N 8.57.
C31H25N3O3. Calculated, %: C 76.37; H 5.17; N 8.62.
1
mineral oil. The H and 13C NMR spectra were
measured on a Bruker AM-400 instrument at 400 and
100 MHz, respectively, using DMSO-d6 as solvent and
tetramethylsilane as internal reference. The reaction
conditions were optimized using a Waters Acquity
UPLC system (BEH C18 column, grain size 1.7 μm;
eluents methanol–water and acetonitrile–water, flow
rate 0.3–0.5 mL/s; ESI MS Xevo TQD detector). The
purity of the products was checked by UPLC and TLC
(Silufol; benzene, ethyl acetate–benzene, 1:5; develop-
ment with iodine vapor).
4-(2,5-Dimethylbenzoyl)-6-(2,5-dimethylphenyl)-
3-hydroxy-8-methyl-1-(4-methylphenyl)-2-oxo-1,7-
diazaspiro[4.4]nona-3,6,8-triene-9-carbonitrile
(IIId). Yield 70%, mp 187–188°C. IR spectrum, ν,
cm–1: 3168 (OH), 2211 (CN), 1703 (C2=O), 1665
1
(4-C=O). H NMR spectrum, δ, ppm: 2.01 s (3H,
CH3), 2.23 s (3H, CH3), 2.24 s (3H, CH3), 2.29 s (6H,
CH3), 2.33 s (3H, CH3), 6.81–7.38 m (10H, Harom),
12.28 br.s (1H, OH). Found, %: C 76.82; H 5.63;
N 8.17. C33H29N3O3. Calculated, %: C 76.87; H 5.67;
N 8.15.
4-(2,5-Dimethylbenzoyl)-6-(2,5-dimethylphenyl)-
3-hydroxy-8-methyl-2-oxo-1-phenyl-1,7-diazaspiro-
[4.4]nona-3,6,8-triene-9-carbonitrile (IIIa). A solu-
tion of 1.0 mmol of compound Ia and 1.0 mmol of
enamine II in 20 mL of anhydrous benzene was heated
for 2 h under reflux, the progress of the reaction being
4-Benzoyl-3-hydroxy-1-(4-methoxyphenyl)-
8-methyl-2-oxo-6-phenyl-1,7-diazaspiro[4.4]nona-
3,6,8-triene-9-carbonitrile (IIIe). Yield 81%,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 6 2014

FIVE-MEMBERED 2,3-DIOXO HETEROCYCLES: CIII.
845
mp 147–148°C. IR spectrum, ν, cm–1: 3185 (OH),
(International Research Teams Competition), and by
the Russian Foundation for Basic Research (project
nos. 12-03-00696, 12-03-31157, 13-03-96009).
1
2206 (CN), 1689 (C2=O), 1660 (4-C=O). H NMR
spectrum, δ, ppm: 2.25 s (3H, CH3), 3.71 s (3H,
OCH3), 6.74–7.96 m (14H, Harom), 12.19 br.s (1H,
OH). Found, %: C 73.29; H 4.41; N 8.81. C29H21N3O4.
Calculated, %: C 73.25; H 4.45; N 8.84.
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(4-methylbenzoyl)-6-(4-methylphenyl)-2-oxo-1,7-di-
azaspiro[4.4]nona-3,6,8-triene-9-carbonitrile (IIIf).
Yield 83%, mp 190–192°C. IR spectrum, ν, cm–1: 3181
(OH), 2205 (CN), 1690 (C2=O), 1661 (4-C=O).
1H NMR spectrum, δ, ppm: 2.26 s (3H, CH3), 2.37 s
(6H, CH3), 3.72 s (3H, OCH3), 6.80–7.82 m (12H,
pirroldiony
(2,3-Dihydropyrrole-2,3-diones),
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H 5.03; N 8.30. C31H25N3O4. Calculated, %: C 73.94;
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 6 2014