Five-membered 2,3-dioxoheterocycles: LXXIX.* three-component condensation of 1h-pyrrol-2,3-diones with acetonitriles and dimedone. crystal and molecular structure of substituted spiro[chromene-4,3′-pyrrole]

Article abstract of DOI:10.1134/S1070428011080082

5-Phenyl-4-ethoxycarbonyl-1H-pyrrole-2,3-diones react with acetonitriles and dimedone to form ethyl 2-amino-7,7-dimethyl-2′,5-dioxo-5′- phenyl-1′,2′,5,6,7,8-hexahydrospiro[chromene-4,3′-pyrrole] -4′-carboxylates. The crystal and molecular structure of eth

Full text of DOI:10.1134/S1070428011080082

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 8, pp. 1165−1168. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © M.V. Dmitriev, P.S. Silaichev, Z.G. Aliev, A.N. Maslivets, 2011, published in Zhurnal Organicheskoi Khimii, 2011, Vol. 47, No. 8,
pp. 1147−1150.
Five-Membered 2,3-Dioxoheterocycles: LXXIX.*
Three-Component Condensation of 1H-Pyrrol-2,3-diones
with Acetonitriles and Dimedone. Crystal and Molecular
Structure of Substituted Spiro[chromene-4,3'-pyrrole]
M. V. Dmitrieva, P. S. Silaicheva,c, Z. G. Alievb, and A. N. Maslivetsa,c
aInstitute of Natural Sciences at Perm State University, Perm, 614990 Russia
e-mail: koh2@psu.ru
bInstitute ofProblems of Chemical Physics, Chernogolovka,
c Perm State University
Received October 26, 2010
Abstract—5-Phenyl-4-ethoxycarbonyl-1H-pyrrole-2,3-diones react with acetonitriles and dimedone to form ethyl
2-amino-7,7-dimethyl-2',5-dioxo-5'-phenyl-1',2',5,6,7,8-hexahydrospiro[chromene-4,3'-pyrrole]-4'-carboxylates.
The crystal and molecular structure of ethyl 2-amino-1'-benzyl-7,7-dimethyl-2',5-dioxo-5'-phenyl-3-cyano-
1',2',5,6,7,8-hexahydrospiro[chromene-4,3'-pyrrole]-4'-carboxylate was proved by XRD analysis.
DOI: 10.1134/S1070428011080082
The three-component condensation of isartin with ace-
tonitriles and β-diketones resulting in 2'-aminospiro[indole-
3,4'-pyran]-2(1H)-ones was reported [2, 3].
of triethylamine for 1.5–3 h (TLC monitoring) to obtain
in good yields ethyl 2-amino-7,7-dimethyl-2',5-dioxo-5'-
phenyl-3-cyano-1',2',5,6,7,8-hexahydrospiro[chromene-
4,3'-pyrrole]-4'-carboxylates IIIa–IIId and 3-methyl
4'-ethyl 2-amino-7,7-dimethyl-2',5-dioxo-5'-phenyl-
1',2',5,6,7,8-hexahydrospiro[chromene-4,3'-pyrrole]-3,4'-
dicarboxylates IIIe–IIIg whose structure was proved by
XRD analysis by an example of compound IIIa.**
We carried out the reaction of 5-phenyl-4-ethoxycar-
bonyl-1H-pyrrole-2,3-diones Ia–Id [4] with substituted
acetonitriles [malononitrile (IIa) and methyl cyanoacetate
(IIb)] and dimedone in the ratio 1 : 1 : 1 by boiling the so-
lution of the reagents in anhydrous benzene in the presence
Me
Me
Me
Me
CN
R2
O
NC
CH2
O
EtOOC
Ph
C R2
EtOOC
Ph
Me
Me
O
OH
CN
OH
IIа,IIb
O
O
_H2O
EtOOC
NH2
EtOOC
Ph
O
O
HC
N
N
R1
OR2
R2
O
Ph
R1
N
N
R1
R1
Iа_Id
IIIа_IIIg
IV
I, R1 = CH2Ph (a), Ph (b), cyclo-C6H11 (c), H (d); II, R2 = CN (a), COOMe (b); III, R2 = CN, R1 = CH2Ph (a), Ph (b),
cyclo-C6H11 (c), H (d); R2 = COOMe, R1 = CH2Ph (e), Ph (f), cyclo-C6H11 (g).
–––––––––––––––––––
* For Communication LXXVIII, see [1].
** For preliminary communication, see [5].
1165

DMITRIEV et al.
1166
methyl protons (0.95–1.09 ppm), doublets of doublets
of nonequivalent methylene protons C8H2 and C6H2
(2.11–2.70 ppm) with characteristic coupling constants
(J 15.6–17.7 Hz), a broadened singlet of NH2 protons
(7.20–7.97 ppm), a triplet and a multiplet of protons of
the ethoxycarbonyl substituent (0.82–1.00 and 3.66–
3.87 ppm respectively).
In the 13C NMR spectra of compounds IIIa and IIIf
characteristic signals were present of the carbon atoms of
the keto carbonyl group (195.23–195.30 ppm), of lactam
carbonyl group (164.11–164.77 ppm), and of the spiro
carbon (43.91–47.45 ppm).
According to XRD data all bond distances and bond
angles in molecule IIIa (Fig. 1) are of the magnitude
common for such bonds. The molecules in the crystal
are bound by two hydrogen bonds. The hydrogen bond
N2–H2a⋯N3 between the amino group and the nitrogen of
the cyano group (bonds N2⋯N3 3.099, H2a⋯N3 2.27 Å,
the angle at the hydrogen atom 173°) leads to the forma-
tion of the centrosymmetrical dimeric associates with the
coordinates of the symmetry center 0.5 0 0. These dimeric
associates are grouped around another symmetry center
with the coordinates 0.5 0.5 0 and are bound by the hy-
drogen bond N2–H2c⋯O3 (bonds N2⋯O3 2.898, H2c⋯O3
1.89 Å, the angle at the hydrogen atom 151°). Thus in the
crystal the molecules are bound by the hydrogen bonds
in endless bands in the direction c of the unit cell. Afrag-
ment of this band is shown in Fig. 2.
Fig. 1. General appearance of molecule of ethyl 2-amino-1'-
benzyl-7,7-dimethyl-2',5-dioxo-5'-phenyl-3-cyano-1',2',5,6,7,8-
hexahydro-spiro[chromene-4,3'-pyrrole]-4'-carboxylate (IIIa).
The formation of compounds IIIa–IIIg proceeds
apparently via the primary condensation of the keto
carbonyl group of pyrrolediones Ia–Id with substituted
acetonitriles IIa, IIb to form pyrrolones IV followed
by the nucleophilic addition of the β-CH group and the
hydroxy group of the enol fragment of dimedone to the
carbon atom in the position 3 and to the cyano group of
pyrrolones IV respectively.
Fig. 2. Schematic view of the hydrogen bond formation in the
crystal of compound IIIa.
Compounds IIIa–IIIg are colorless high-melting crys-
talline substances, readily soluble in DMSO and DMF,
sparingly soluble in ordinary organic solvents, insoluble
in alkanes and water, giving a negative test for enol hy-
droxy group with the ethanol solution of iron(III) chloride.
The reaction described is a rare example of the
spiro-bis-heterocyclization of monocyclic 1H-pyrrole-
2,3-diones in the three-component condensation with
nucleophilic reagents, and also an example of the syn-
thesis of difficultly accessible heterocyclic system of
spiro[chromene-4,3'-pyrrole].
The IR spectra of compounds IIIa–IIIg contain the
absorption bands of the stretching vibrations of the NH2
group, (3154–3453 cm–1), cyano group (2189–2199 cm–1)
(in compounds IIIa–IIId), of lactam carbonyl group
(1694–1734 cm–1), ester and keto carbonyl groups
(1657–1694 cm–1).
EXPERIMENTAL
1
IR spectra of compounds obtained were recorded on
a spectrophotometer FSM -1201 from mulls in mineral
oil. 1H and 13C NMR spectra were registered on a spec-
In the H NMR spectra of compounds IIIa–IIIg
alongside the proton signals of the aromatic rings and
the groups attached thereto two singlets appeared of the
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FIVE-MEMBERED 2,3-DIOXOHETEROCYCLES: LXXIX.
1167
trometer Bruker AM-400 [400 (1H) and 100 (13C) MHz]
in DMSO-d6, internal reference TMS. The homogeneity
of compounds obtained was proved by TLC on Silufol
plates, eluents benzene–ethyl acetate, 5 : 1, ethyl acetate,
development in iodine vapor.
Ethyl 2-amino-7,7-dimethyl-2',5-dioxo-1',5'-diphe-
nyl-3-cyano-1',2',5,6,7,8-hexahydrospiro-[chromene-
4,3'-pyrrole]-4'-carboxylate (IIIb). Yield 74%, mp
243–244°C (ethyl acetate–acetone, 1 : 1). IR spectrum, ν,
cm–1: 3453, 3279, 3167 (NH2), 2199 (CN), 1721 (C2'=O),
1690 (COO), 1663 (C5=O). 1H NMR spectrum, δ, ppm:
0.91 t (3H, CH2CH3, J 7.2 Hz), 1.02 C (3H, Me), 1.09 C
(3H, Me), 2.23 d, 2.35 d (2H, C8H2, J 16.4 Hz), 2.41 d,
2.69 d (2H, C6H2, J 17.3 Hz), 3.83 m (2H, OCH2CH3),
7.02–7.32 group of signals (10H, 2Ph), 7.40 br.s (2H,
NH2). Found, %: C 70.73; H 5.43; N 8.13. C30H27N3O5.
Calculated, %: C 70.71; H 5.34; N 8.25.
XRD investigation of compound IIIa. Colorless
crystals C31H29N3O5, well formed tetragonal prisms
belonging to monoclinic crystal system: a 13.753(3),
b 9.398(2), c 21.610(4) Å, β 98.77(3), V 2760.5(10) Å3,
M 523.57, dcalc 1.260 g/cm3, Z 4, space group P2(1)/C.
The set of experimental reflections was obtained on
an automatic four-circle diffractometer QM-4 (KUMA
DIFFRACTION) with χ-geometry by ω/2Θ scanning
with the use of monochromatized MOKα-radiation (2Θ ≤
52°). Overall number of measured reflections 5589,
among them 5433 independent reflections (Rint 0.0229).
No correction for extinction was done (μ 0.086 mm–1).
The structure was solved by the direct method applying
the program SIR92 [6] followed by a series of calcula-
tions of the electron density maps. Hydrogen atoms
were placed geometrically. The full-matrix least-squares
anisotropic refinement of nonhydrogen atoms along the
program SHELXL-97 [7] was finished at R1 0.0570 and
wR2 0.11524 for 2278 reflections with I ≥ 2σ(I). Refined
parameters 361, Δρmax 0.249, GOOF 0.890.
Ethyl 2-amino-7,7-dimethyl-2',5-dioxo-
5'-phenyl-3-cyano-1'-cyclohexyl-1',2',5,6,7,8-
hexahydrospiro[chromene-4,3'-pyrrole]-4'-car-
boxylate (IIIc). Yield 78%, mp 235–236°C (toluene).
IR spectrum, ν, cm–1: 3399, 3297, 3162 (NH2), 2186
(CN), 1715 (C2'=O), 1690 (COO), 1665 (C5=O).
1H NMR spectrum, δ, ppm: 0.82 t (3H, CH2CH3,
J 7.0 Hz), 0.88–2.08 group of signals (10H, C6H11),
0.98 s (3H, Me), 1.07 s (3H, Me), 2.16 d, 2.30 d
(2H, C8H2, J 16.0 Hz), 2.36 d, 2.63 d (2H, C6H2,
J 17.6 Hz), 3.04 m (1H, NCH), 3.72 m (2H, CH2CH3),
7.24–7.52 group of signals (7H, Ph + NH2). Found, %:
C 69.99; H 6.29; N 8.26. C30H33N3O5. Calculated, %:
C 69.88; H 6.45; N 8.15.
Ethyl 2-amino-1'-benzyl-7,7-dimethyl-2',5-di-
oxo-5'-phenyl-3-cyano-1',2',5,6,7,8-hexahydro-
spiro[chromene-4,3'-pyrrole]-4'-carboxylate (IIIa).
To a solution of 1 mmol of pyrroledione Ia in 20 ml of
anhydrous benzene was added 1 mmol of malononitrile,
1 mmol of dimedone, and 1 mmol of triethylamine, the
mixture was boiled for 2 h, cooled, the formed precipitate
was filtered off and recrystallized from toluene. Yield
89%, mp 243–244°C. IR spectrum, ν, cm–1: 3399, 3328,
3214 (NH2), 2191 (CN), 1734 (C2'=O), 1674 (COO,
C5=O). 1H NMR spectrum, δ, ppm: 0.84 t (3H, CH2CH3,
J 7.4 Hz), 1.01 s (3H, Me), 1.08 s (3H, Me), 2.22 d,
2.35 d (2H, C8H2, J 15.6 Hz), 2.40 d, 2.69 d (2H, C6H2,
J 17.7 Hz), 3.77 m (2H, OCH2CH3), 4.47 s (2H, CH2Ph),
7.06–7.41 group of signals (12H, 2Ph + NH2). 13C NMR
spectrum, δ, ppm: 13.41 (CH3CH2), 26.19 (Me), 28.15
(Me), 31.91 (C7), 39.89 (C8), 43.91 (C4), 47.71 (CH2Ph),
49.80 (C6), 55.05 (C3), 58.75 (CH3CH2), 110.19 (C4'),
111.32 (C4a), 117.52 (CN), 126.47–136.51 (Carom), 154.70
(C5'), 159.77 (C8a), 161.48 (C2), 164.77 (C2'), 178.63
(COO), 195.30 (C5). Found, %: C 71.02; H 5.47; N 8.08.
C31H29N3O5. Calculated, %: C 71.11; H 5.58; N 8.03.
Ethyl 2-amino-7,7-dimethyl-2',5-dioxo-5'-phenyl-
3-cyano-1',2',5,6,7,8-hexahydrospiro-[chromene-
4,3'-pyrrole]-4'-carboxylate (IIId). Yield 79%, mp
263–265°C (toluene–1,4-dioxane, 1:1). IR spectrum,
ν, cm–1: 3395, 3318, 3194 (NH2), 2189 (CN), 1728
1
(C2'=O), 1682 (COO), 1661 (C5=O). H NMR spec-
trum, δ, ppm: 0.98 s (3H, Me), 1.00 t (3H, CH2CH3,
J 7.5 Hz), 1.06 s (3H, Me), 2.14 d, 2.29 d (2H, C8H2,
J 16.1 Hz), 2.36 d, 2.63 d (2H, C6H2, J 17.6 Hz), 3.87 m
(2H, CH2CH3), 7.14–7.51 group of signals (7H, Ph +
NH2), 10.72 s (1H, NH). Found, %: C 66.64; H 5.28;
N 9.81. C24H23N3O5. Calculated, %: C 66.50; H 5.35;
N 9.69.
3-Methyl 4'-ethyl 2-amino-1'-benzyl-7,7-dimeth-
yl-2',5-dioxo-5'-phenyl-1',2',5,6,7,8-hexahydro-
spiro[chromene-4,3'-pyrrole]-3,4'-dicarboxylate
(IIIe). Yield 74%, mp 235–236°C (toluene). IR spectrum,
cm-1: 3366, 3244, 3154 (NH2), 1725, 1690 (C2'=O, COO),
1
1663 (C5=O). H NMR spectrum, δ, ppm: 0.86 t (3H,
CH2CH3, J 7.0 Hz), 0.97 s (3H, Me), 1.08 s (3H, Me),
2.18 d, 2.35 d (2H, C8H2, J 16.1 Hz), 2.36 d, 2.69 d
(2H, C6H2, J 17.7 Hz), 3.32 s (3H, COOMe), 3.71 m
Compounds IIIb–IIIg were synthesized analogously.
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DMITRIEV et al.
1168
(2H, CH2CH3), 4.39 d, 4.45 d (2H, CH2Ph, J 15.8 Hz),
7.09–7.45 group of signals (10H, 2Ph), 7.97 br.s (2H,
NH2). Found, %: C 69.07; H 5.91; N 4.92. C32H32N2O7.
Calculated, %: C 69.05; H 5.79; N 5.03.
(10H, C6H11), 0.95 s (3H, Me), 1.06 s (3H, Me), 2.11 d,
2.30 d (2H, C8H2, J 16.0 Hz), 2.32 d, 2.64 d (2H, C6H2,
J 16.8 Hz), 3.07 m (1H, NCH), 3.58 s (3H, COOMe),
3.66 m (2H, CH2CH3), 7.16–7.50 group of signals (5H, Ph),
7.90 br.s (2H, NH2). Found, %: C 67.80; H 6.77; N 5.02.
C31H36N2O7. Calculated, %: C 67.87; H 6.61; N 5.11.
3-Methyl 4'-ethyl 2-amino-7,7-dimethyl-2',5-
dioxo-1',5'-diphenyl-1',2',5,6,7,8-hexahydrospiro-
[chromene-4,3'-pyrrole]-3,4'-dicarboxylate (IIIf).
Yield 63%, mp 230–232°C (toluene). IR spectrum, ν,
cm–1: 3332, 3247, 3169 (NH2), 1694 (C2'=O, COO), 1657
(C5=O). 1H NMR spectrum, δ, ppm: 0.92 t (3H, CH2CH3,
J 7.1 Hz), 0.99 s (3H, Me), 1.08 s (3H, Me), 2.20 d,
2.35 d (2H, C8H2, J 15.8 Hz), 2.38 d, 2.70 d (2H, C6H2,
J 17.5 Hz), 3.66 s (3H, COOMe), 3.77 m (2H, CH2CH3),
7.08–7.30 group of signals (10H, 2Ph), 7.96 br.s (2H,
NH2). 13C NMR spectrum, δ, ppm: 13.51 (CH3CH2),
25.87 (Me), 28.39 (Me), 31.63 (C7), 40.11 (C8), 47.45
(C4), 50.42 (C6), 50.67 (COOMe), 58.87 (CH3CH2), 74.43
(C3), 109.70 (C4'), 112.30 (C4a), 125.21–134.95 (Carom),
154.43 (C5'), 160.22 (C8a), 162.12 (C2), 164.11 (C2'),
167.58 (COOMe), 179.46 (COOEt), 195.23 (C5). Found,
%: C 68.79; H 5.51; N 5.09. C31H30N2O7. Calculated, %:
C 68.62; H 5.57; N 5.16.
ACKNOWLEDGMENTS
The study was performed under the financial support
of the Ministry of Education and Science of the Russian
Federation (project no. 2.19.10) and the Russian Founda-
tion for Basic Research (grant no. 08-03-01032).
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dioxo-5'-phenyl-1'-cyclohexyl-1',2',5,6,7,8-hexa-
hydrospiro[chromene-4,3'-pyrrole]-3,4'-dicarboxylate
(IIIg). Yield 66%, mp 247–250°C (toluene). IR spec-
trum, ν, cm–1: 3355, 3239, 3171 (NH2), 1694 (C2'=O,
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