Spirocyclohexadienones: XII. Dienone-phenol rearrangement of 1-substituted 2-azaspiro[4.5]undeca-1,6,9-trienes and their analogs

Article abstract of DOI:10.1134/S1070428011090107

Hydrolytic cleavage of 1-substituted 2-azaspiro[4.5]undeca-1,6,9-trienes in acid medium is accompanied by dienone-phenole rearrangement with formation of substituted N-[2-(p-hydroxyphenyl)ethyl] carboxylic acid amides. 1,2-Dimethoxy-3-oxo-15-phenyl-14-aza

Full text of DOI:10.1134/S1070428011090107

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 9, pp. 1318–1322. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © V.A. Glushkov, E.V. Rotermel’, T.F. Odegova, Yu.V. Shklyaev, 2011, published in Zhurnal Organicheskoi Khimii, 2011, Vol. 47,
No. 9, pp. 1301–1305.
Spirocyclohexadienones: XII.* Dienone–Phenol Rearrangement
of 1-Substituted 2-Azaspiro[4.5]undeca-1,6,9-trienes
and Their Analogs
V. A. Glushkova, E. V. Rotermel’a, T. F. Odegovab, and Yu. V. Shklyaeva
a Institute of Technical Chemistry, Ural Division, Russian Academy of Sciences,
ul. Akademika Koroleva 3, Perm, 614013 Russia
e-mail: glusha55@gmail.com
b Perm State Pharmaceutical Academy
Received February 11, 2011
Abstract—Hydrolytic cleavage of 1-substituted 2-azaspiro[4.5]undeca-1,6,9-trienes in acid medium is accom-
panied by dienone–phenole rearrangement with formation of substituted N-[2-(p-hydroxyphenyl)ethyl]
carboxylic acid amides. 1,2-Dimethoxy-3-oxo-15-phenyl-14-azadispiro[5.1.5.2]pentadeca-1,4,14-triene and
2′-R-7a′-methyl-3a′,4′,5′,6′,7′,7a′-hexahydrospiro[cyclohexa[2,5]diene-1,3′-indol]-4-ones undergo analogous
cleavage.
DOI: 10.1134/S1070428011090107
It is known that three-component condensation of
anisole derivatives with isobutyraldehyde and nitriles
leads to the formation of substituted 2-azaspiro[4.5]-
undeca-1,6,9-trienes [1, 2]. Analogous reaction with
cyclohexanecarbaldehyde yields dispiro compounds
[3]. 1- and 2-Methoxynaphthalenes behave in a similar
way [4], whereas 2-methyl-1-(p-methoxyphenyl)-
cyclohexan-1-ol gives rise to 2′-substituted 7a′-methyl-
3a′,4′,5′,6′,7′,7a′-hexahydrospiro[cyclohexa[2,5]diene-
1,3′-indol]-4-ones [5]. The above listed spiro com-
pounds characteristically undergo hydrolytic cleavage
in acid medium, which is accompanied by dienone–
phenol rearrangement with formation of substituted
N-[2-(p-hydroxyphenyl)ethyl] carboxylic acid amides
[6]. Such rearrangement of spiro cyclohexadienone
derivatives having no substituents in the cyclohexane
ring was studied by us previously, and its mechanism
was analyzed by quantum-chemical calculations [6, 7].
The goal of the present work was to study dienone–
phenol rearrangement of substituted 2-azaspiro[4.5]-
undeca-1,6,9-trienes and structurally related
2′-R-7a′-methyl-3a′,4′,5′,6′,7′,7a′-hexahydrospiro-
[cyclohexa[2,5]diene-1,3′-indol]-4-ones. The reactions
were carried out by heating the initial spiro compound
for a short time (0.5 h) in aqueous ethanol containing
concentrated sulfuric acid. The presence of methoxy
groups in the cyclohexadiene ring of 2-azaspiro[4.5]-
undeca-6,9-dienes and 2-azaspiro[4.5]undeca-1,6,9-tri-
enes did not affect the reaction course, and the process
occurred in a way similar to hydrolytic cleavage of
spiro compounds derived from anisole which had no
substituents in the cyclohexadiene ring [6] (Scheme 1).
Scheme 1.
Me
NH
R1
Me
R1
H
R2
N
OEt
H+, H2O
R2
O
O
Me
R3
Me
O
O
HO
OEt
R3
Ia–Ic
R1 = R2 = MeO, R3 = H (a); R1 = H, R2 = R3 = MeO (b); R1 = R3 = MeO, R2 = H (c).
* For communication XI, see [1].
1318

SPIROCYCLOHEXADIENONES: XII.
1319
Scheme 2.
Me
R1
Me
R1
H
N
R2
O
H+, H2O
N
R2
O
Me
R3
Me
Ar
Ar
HO
R3
IIa–IIi
R1 = R2 = MeO, R3 = H, Ar = 4-MeOC6H4 (a); R1 = R2 = MeO, R3 = H, Ar = 3,4-(MeO)2C6H3 (b); R1 = H, R2 = R3 = MeO, Ar =
Ph (c); R1 = H, R2 = R3 = MeO, Ar = 3,4-(MeO)2C6H3 (d); R1 = H, R2 = R3 = MeO, Ar = 4-BrC6H4 (e); R1 = R3 = MeO, R2 = H, Ar =
Ph (f); R1 = R3 = OMe, R2 = H, Ar = 4-MeOC6H4 (g); R1 = R3 = MeO, R2 = H, Ar = 3,4-(MeO)2C6H3 (h); R1 = R3 = MeO, R2 = H,
Ar = 4-BrC6H4 (i).
Hydrolysis of dispiro compounds, e.g., of 1,2-di-
methoxy-15-phenyl-14-azadispiro[5.1.5.2]pentadeca-
1,4,14-trien-3-one [3]) involved opening of the central
pyrrole ring (Scheme 3). Fusion of a benzene ring to
the cyclohexadiene fragment increases stability of the
spirocyclic system. Benzo-fused 2-azaspiro[4.5]un-
deca-6,9-dienes and -1,6,9-trienes obtained from
1- and 2-methoxynaphthalenes [4] did not undergo
rearrangement under analogous conditions; their
hydrolysis required more sever conditions and was not
selective.
The structure of amides Ia–Ic thus obtained was
confirmed by their IR and H NMR spectra. Crystal-
1
line samples of Ia–Ic displayed in the IR spectra
a broad absorption band at ~3330–3340 cm–1 due to
stretching vibrations of the phenolic hydroxy group
and amide NH group and strong absorption bands at
1736–1742 and 1652–1660 cm–1, belonging to stretch-
ing vibrations of the ester and amide carbonyl groups,
respectively. Ring opening in unsymmetrically substi-
tuted 6,7-dimethoxy-2-azaspiro[4.5]undeca-6,9-dien-8-
one (Scheme 1, R1 = R2 = MeO) with formation of
compound Ia was accompanied by transformation of
the doublet from diastereotopic protons on C4 (δ 1.99
and 2.40 ppm) into a singlet at δ 2.82 ppm and of two
signals from nonequivalent methyl groups on C3
(δ 1.42 and 1.43 ppm) into one singlet at δ 1.35 ppm.
Substituted spiro[cyclohexa[2,5]diene-1,3′-indol]-
4-ones have recently attracted researchers’ attention
[8]. Rearrangement of one of these compounds, ethyl
(Z)-2-{7a′-methyl-4-oxo-3a′,4′,5′,6′,7′,7a′-hexahydro-
spiro[cyclohexa[2,5]diene-1,3′-indol]-2′(1′H)-ylidene}-
acetate synthesized by us previously [5], followed
a similar pattern and produced N-substituted malon-
amic acid ester IV (Scheme 4). Likewise, hydrolysis
of 7a′-methyl-2′-phenyl-3a′,4′,5′,6′,7′,7a′-hexahydro-
1-Aryl-2-azaspiro[4.5]undeca-1,6,9-trienes [1] re-
acted in a similar way (Scheme 2), and the yields of
amides IIa–IIi were 44–86%. In the IR spectra of IIa–
IIi (crystalline samples), broadened absorption bands
due to stretching vivrations of the phenolic hydroxy
group (3348–3579 cm–1) and amide NH group (3215–
3414 cm–1) were observed together with strong absorp-
tion band belonging to the amide carbonyl group
(1645–1650 cm–1). As in the previous case, doublets
Scheme 4.
OH
O
H+, H2O
1
from diastereotopic protons on C4 in the H NMR
Me
NH
HN
spectra of unsymmetrically substituted initial com-
pounds were converted into singlets at δ 2.79–
2.84 ppm (IIa–IIe), and two singlets from geminal
methyl groups on C3 were transformed into one singlet
at δ 1.50–1.52 ppm.
Me
O
OEt
OH
O
OEt
O
IV
Scheme 5.
O
Scheme 3.
OMe
H+, H2O
MeO
H+, H2O
OMe
NH
Me
HN
Me
MeO
N
N
HO
Ph
Ph
O
O
Ph
O
III
V
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 9 2011

GLUSHKOV et al.
1320
spiro[cyclohexa[2,5]diene-1,3′-indole]-4-one afford-
ed substituted benzamide V (Scheme 5).
ν, cm–1 (film): 3339 (OH, NH), 3089, 2976, 2937,
2833, 1738 (C=O), 1660 (C=O), 1551, 1495 (C=S),
1467, 1422, 1367, 1340, 1301, 1195, 1173, 1067,
Biological assay of compounds Ib and IIf–IIh
revealed their weak antimicrobial activity against
S. aureus R 209 (the minimal inhibitory concentration
of compound Ib was 125 μg/ml, and of IIf–IIh, ~500–
1000 μg/ml) and E. coli (500 μg/ml for Ib, and
1000 μg/ml for IIf–IIh); compound IIi showed no
antimicrobial activity.
1
1031, 756. H NMR spectrum, δ, ppm: 1.24 t (3H,
CH3CH2, J = 7.2 Hz), 1.35 s (6H, Me), 2.82 s (2H,
CH2Ar), 3.17 s (2H, COCH2), 3.84 s and 3.89 s (3H
each, OMe), 4.14 q (2H, OCH2, J = 7.2 Hz), 5.96 s
(1H, NH), 6.64 d (1H, 5-H, J = 8.4 Hz), 6.73 d (1H,
6-H, J = 8.4 Hz), 7.04 br.s (1H, OH). Found, %:
C 53.60; H 6.95; N 3.48. C17H25NO6·2.5H2O. Calcu-
lated, %: C 53.11; H 7.86; N 3.64.
EXPERIMENTAL
Ethyl N-[2-(4-hydroxy-2,5-dimethoxyphenyl)-
1,1-dimethylethyl]malonamate (Ib). Yield 67%,
colorless crystals, mp 124–125°C, Rf 0.44. IR spec-
trum, ν, cm–1 (mineral oil): 3332 (NH), 3111 br (OH),
1742 (C=O, ester), 1652 (C=O, amide), 1606 w, 1573,
The IR spectra were recorded on a Bruker IFS 66ps
spectrometer with Fourier transform from samples
dispersed in mineral oil or thin films obtained by
1
evaporation of a solution in chloroform. The H NMR
spectra were measured on a Varian Mercury 300 in-
strument at 300 MHz from solutions in CDCl3; the
chemical shifts were determined relative to hexa-
methyldisiloxane (δ 0.055 ppm). The mass spectra
(electron impact, 70 eV) were obtained on an Agilent
GC–MS system consisting of an HP 6890N gas chro-
matograph coupled with an HP 5975B mass-selective
detector. The elemental compositions were determined
on a Leco CHNS 9321P analyzer. The Rf values were
measured on Sorbfil plates (silica gel) using chloro-
form–acetone (9:1) as eluent; spots were visualized
under UV light or by treatment with a 2% solution of
tetrachloro-1,4-benzoquinone in toluene and subse-
quent heating. Column chromatography was performed
using Silica gel 60 (220–440 Mesh, Alfa Aesar). Com-
mercial 1,2,3-, 1,2,4-, and 1,3,5-trimethoxybenzenes
and isobutyraldehyde (Alfa Aesar, Lancaster) were
used.
General procedure for the hydrolysis of spiro-
cyclic compounds. The corresponding substrate,
1 mmol, was dissolved in a mixture of 15 ml of alco-
hol, 5 ml of water, and 1 ml of concentrated sulfuric
acid, and the mixture was heated for 0.5 h under reflux
and poured into 50 ml of a saturated solution of
sodium hydrogen carbonate (until pH ~7). If a solid
separated, it was filtered off, dried, and recrystallized
from hexane–ethyl acetate. Oily compounds Ia, IId,
and IIe were extracted into 50 ml of CH2Cl2, the
extract was dried over MgSO4 and evaporated, and the
residue was purified by chromatography on silica gel
using petroleum ether (bp 40–70°C)–ethyl acetate
(5:1) as eluent.
1
1523, 1318, 1208, 1170, 1041, 967 w, 864. H NMR
spectrum, δ, ppm: 1.17 t (3H, CH3CH2, J = 7.2 Hz),
1.31 s (6H, Me), 2.78 s (2H, CH2Ar), 3.10 s (2H,
COCH2), 3.71 s and 3.76 s (3H each, OMe), 4.04 q
(2H, OCH2, J = 7.2 Hz), 5.76 s (1H, NH), 6.51 s (1H,
3-H), 6.57 s (1H, 6-H), 7.21 br.s (1H, OH). Found, %:
C 59.98; H 7.40; N 4.09. C17H25NO6. Calculated, %:
C 60.16; H 7.42; N 4.13.
Ethyl N-[2-(4-hydroxy-2,6-dimethoxyphenyl)-
1,1-dimethylethyl]malonamate (Ic). Yield 24%, light
yellow oily substance, Rf 0.20. IR spectrum, ν, cm–1
(film): 3337 (OH, NH), 2977, 2937, 2842, 1736
(C=O), 1666 (C=O), 1596 (C=C), 1558, 1472, 1373,
1
1308, 1208, 1152, 1103, 1038, 1000, 819. H NMR
spectrum, δ, ppm: 1.24 t (3H, CH3CH2, J = 7.2 Hz),
1.39 s (6H, Me), 2.77 s (2H, CH2Ar), 3.10 s (2H,
COCH2), 3.75 s and 3.80 s (3H each, OMe), 4.15 q
(2H, OCH2, J = 7.2 Hz), 6.15 s (2H, 3-H, 5-H),
7.38 br.s (1H, NH), 7.54 br.s (1H, OH). Found, %:
C 59.97; H 7.36; N 4.04. C17H25NO6. Calculated, %:
C 60.16; H 7.42; N 4.13.
N-[2-(4-Hydroxy-2,3-dimethoxyphenyl)-1,1-di-
methylethyl]-4-methoxybenzamide (IIa). Yield 88%,
mp 135–136°C. IR spectrum, ν, cm–1: 3395 (OH),
3318 (NH), 1645 (C=O), 1609 (C=C), 1572, 1540,
1499, 1303, 1280, 1257, 1184, 1129, 1065, 1029, 933,
1
846, 823, 764, 695. H NMR spectrum, δ, ppm: 1.50 s
(6H, Me), 2.79 s (2H, CH2), 3.81 s (3H, OMe), 3.90 s
(3H, OMe), 3.93 s (3H, OMe), 6.06 br.s (1H, NH),
6.68 d (1H, 5′-H, J = 8.4 Hz), 6.78 d (1H, 6′-H, J =
8.4 Hz), 6.84 d (2H, 3-H, 5-H, J = 9 Hz), 7.26 br.s (1H,
OH), 7.74 d (2H, 2-H, 6-H, J = 9 Hz). Found, %:
C 66.87; H 6.88; N 3.84. C20H25NO5. Calculated, %:
C 66.84; H 7.01; N 3.90.
Ethyl N-[2-(4-hydroxy-2,3-dimethoxyphenyl)-
1,1-dimethylethyl]malonamate hydrate (Ia). Yield
80%, light yellow oily substance, Rf 0.40. IR spectrum,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 9 2011

SPIROCYCLOHEXADIENONES: XII.
1321
N-[2-(4-Hydroxy-2,3-dimethoxyphenyl)-1,1-di-
methylethyl]-3,4-dimethoxybenzamide hydrate
(IIb). Yield 76%, mp 97–100°C. IR spectrum, ν, cm–1:
3551 (OH), 3377 (NH), 1645 (C=O), 1604 (C=C),
1586, 1545, 1504, 1307, 1266, 1230, 1193, 1184, 1134,
N-[2-(4-Hydroxy-2,6-dimethoxyphenyl)-1,1-di-
methylethyl]-4-methoxybenzamide (IIg). Yield 86%,
mp 174–175°C. IR spectrum, ν, cm–1: 3450 (OH),
3414 (NH), 1649 (C=O), 1624 (C=C), 1606, 1592,
1513, 1314, 1285, 1262, 1238, 1217, 1183, 1171, 1158,
1029, 942, 873, 838. 1H NMR spectrum, δ, ppm: 1.48 s
(6H, Me), 2.27 s (2H, CH2), 3.64 s (6H, OMe), 3.78 s
(3H, OMe), 5.55 s (2H, 3′-H, 5′-H), 6.75 s (1H, 3-H),
6.76 s (1H, 5-H), 6.77 s (1H, 2-H), 6.78 s (1H, 6-H),
1
1115, 1070, 1038, 1024, 960, 864, 818, 759. H NMR
spectrum, δ, ppm: 1.51 s (6H, Me), 2.80 s (2H, CH2),
3.89 s (6H, OMe), 3.91 s (3H, OMe), 3.94 s (3H,
OMe), 6.02 br.s (1H, NH), 6.68 d (1H, 5′-H, J =
8.1 Hz), 6.77 m (2H, 5-H, 6′-H), 7.28 m (2H, 6-H,
OH), 7.46 d (1H, 2-H, J = 2.4 Hz). Found, %: C 62.06;
H 6.83; N 3.84. C21H27NO6 ·H2O. Calculated, %:
C 61.90; H 7.17; N 3.44.
4
7.63 d (2H, 3-H, 5-H, J = 2.1 Hz), 7.65 d (2H, 2-H,
6-H, J = 1.8 Hz); NH and OH signals were not ob-
served because of fast proton exchange. Found, %:
C 67.04; H 6.77; N 3.94. C20H25NO5. Calculated, %:
C 66.84; H 7.01; N 3.90.
N-[2-(4-Hydroxy-2,5-dimethoxyphenyl)-1,1-di-
methylethyl]benzamide (IIc). Yield 14%, mp 156–
N-[2-(4-Hydroxy-2,6-dimethoxyphenyl)-1,1-di-
methylethyl]-3,4-dimethoxybenzamide (IIh). Yield
67%, mp 157–159°C. IR spectrum, ν, cm–1: 3579
(OH), 3407 (NH), 1650 (C=O), 1624 (C=C), 1586,
1522, 1418, 1319, 1269, 1239, 1225, 1170, 1156,
1
157°C. H NMR spectrum, δ, ppm: 1.52 s (6H, Me),
2.87 s (2H, CH2), 3.74 s and 3.78 s (3H each, OMe),
5.70 br.s (1H, NH), 6.60 s (1H, 3′-H), 6.63 s (1H,
6′-H), 7.13 s (1H, OH), 7.39 m (3H, 3-H, 4-H, 5-H),
7.64 m (2H, 2-H, 6-H). Found, %: C 69.17; H 6.64;
N 4.20. C19H23NO4. Calculated, %: C 69.28; H 7.04;
N 4.25.
1
1064, 1026, 848. H NMR spectrum, δ, ppm: 1.46 s
(6H, Me), 2.28 s (2H, CH2), 3.65 s (6H, OMe), 3,84 s
(3H, OMe), 3.85 s (3H, OMe), 5.56 s (2H, 3′-H, 5′-H),
3
3
N-[2-(4-Hydroxy-2,5-dimethoxyphenyl)-1,1-di-
methylethyl]-3,4-dimethoxybenzamide (IId). Yield
6.69 d (1H, 2-H, J = 8.4 Hz), 7.18 d.d (1H, 6-H, J =
4
4
8.4, J = 2.1 Hz), 7.42 d (1H, 5-H, J = 2.1 Hz); NH
and OH signals were not observed because of fast
proton exchange. Found, %: C 64.59; H 6.96; N 3.62.
C21H27NO6. Calculated, %: C 64.77; H 6.99; N 3.60.
1
75%, light yellow oily substance. H NMR spectrum,
δ, ppm: 1.52 s (6H, Me), 2.88 s (2H, CH2), 3.74 s (3H,
OMe), 3.80 s (3H, OMe), 3.90 s (6H, OMe), 5.69 br.s
(1H, NH), 6.61 s (1H, 3′-H), 6.64 s (1H, 6′-H), 6.79 d
3
4-Bromo-N-[2-(4-hydroxy-2,6-dimethoxy-
phenyl)-1,1-dimethylethyl]benzamide (IIi). Yield
66%, mp 136–140°C. IR spectrum, ν, cm–1: 3361 br
(NH, OH), 1649 (C=O), 1626 (C=C), 1592, 1285,
1238, 1215, 1158, 1069, 1005, 856, 834, 737, 719.
1H NMR spectrum, δ, ppm: 1.45 s (6H, Me), 2.29 s
(2H, CH2), 3.65 s (6H, OMe), 5.55 s (2H, 3′-H, 5′-H),
7.39 d (2H, 3-H, 5-H, J = 9.0 Hz), 7.55 d (2H, 2-H,
6-H, J = 9.0 Hz); NH and OH signals were not ob-
served because of fast proton exchange. Found, %:
C 56.05; H 5.46; N 3.36. C19H22BrNO4. Calculated, %:
C 55.89; H 5.43; N 3.43.
(1H, 5-H, J = 8.4 Hz), 7.02 s (1H, OH), 7.14 d.d
3
4
(1H, 6-H, J = 8.4, J = 1.8 Hz), 7.40 d (1H, 2-H,
4J = 1.8 Hz). Found, %: C 64.68; H 7.05; N 3.52.
C21H27NO6. Calculated, %: C 64.77; H 6.99; N 3.60.
4-Bromo-N-[2-(4-hydroxy-2,5-dimethoxyphenyl)-
1,1-dimethylethyl]benzamide (IIe). Yield 81%, light
1
yellow oily substance. H NMR spectrum, δ, ppm:
1.52 s (6H, Me), 2.84 s (2H, CH2), 3.76 s and 3.78 s
(3H each, OMe), 5.89 br.s (1H, NH), 6.61 s (1H, 3′-H),
6.62 s (1H, 6′-H), 7.25 s (1H, OH), 7.53 m (4H, Harom).
Found, %: C 55.69; H 5.65; N 3.42. C19H22BrNO4.
Calculated, %: C 55.89; H 5.43; N 3.43.
N-[1-(4-Hydroxy-2,3-dimethoxybenzyl)cyclo-
hexyl]benzamide (III). Yield 82%, colorless crystals,
mp 61–65°C, Rf 0.52. IR spectrum, ν, cm–1 (film):
3352 br (NH, OH), 3060, 3005, 2932, 2856, 1649
(C=O), 1602 (C=C), 1578 w, 1534, 1493, 1447, 1423,
1350, 1334, 1289, 1198, 1091, 1062, 1025, 755.
1H NMR spectrum, δ, ppm: 1.37–1.59 m (8H, CH2),
2.37 m (2H, CH2), 3.05 s (2H, ArCH2), 3.82 s and
3.83 s (3H each, OMe), 5.78 s (1H, NH), 6.00 br.s (1H,
OH), 6.58 d (1H, 5′-H, J = 7.8 Hz), 6.74 d (1H, 6′-H,
J = 7.8 Hz), 7.34–7.47 m (3H, 3-H, 4-H, 5-H), 7.71 d.d
N-[2-(4-Hydroxy-2,6-dimethoxyphenyl)-1,1-di-
methylethyl]benzamide (IIf). Yield 86%, mp 177–
179°C. IR spectrum, ν, cm–1: 3348 (OH), 3215 (NH),
1646 (C=O), 1617 (C=C), 1584, 1284, 1232, 1210,
1181, 1158, 1141, 1101, 1064, 997, 937, 853, 777, 715.
1H NMR spectrum, δ, ppm: 1.46 s (6H, Me), 2.29 s
(2H, CH2), 3.65 s (6H, OMe), 5.55 s (2H, 3′-H, 5′-H),
7.28 m (3H, 3-H, 4-H, 5-H), 7.66 m (2H, 2-H, 6-H);
NH and OH signals were not observed because of fast
proton exchange. Found, %: C 69.20; H 6.95; N 4.19.
C19H23NO4. Calculated, %: C 69.28; H 7.04; N 4.25.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 9 2011

GLUSHKOV et al.
1322
3
4
(2H, 2-H, 6-H, J = 8.4, J = 1.8 Hz). Found, %:
C 71.48; H 7.44; N 3.65. C22H27NO4. Calculated, %:
C 71.52; H 7.37; N 3.79.
The authors thank V.I. Karmanov and I.A. Borisova
for recording the IR spectra, O.A. Maiorova for
recording the NMR spectra, and E.V. Baigacheva for
performing elemental analysis. This study was per-
formed under financial support by the Presidium of the
Russian Academy of Sciences (program no. 21) and by
a joint program of the Ural and Siberian Divisions of
the Russian Academy of Sciences.
Ethyl N-[2-(4-hydroxyphenyl)-1-methylcyclo-
hexyl]malonamate hemihydrate (IV). Yield 64%,
light yellow crystals, mp 99–103°C, Rf 0.34. IR spec-
trum, ν, cm–1 (film): 3348 br (NH, OH), 2979, 2931,
2858, 1723 (C=O, ester), 1659 (C=O, amide), 1614
(C=C), 1592 w, 1537, 1480, 1446, 1372, 1336, 1234,
REFERENCES
1
1180, 1032, 832, 757. H NMR spectrum, δ, ppm:
3
3
1.27 t (1.5H, Me, J = 6.9 Hz), 1.28 t (1.5H, Me, J =
6.9 Hz), 1.32–2.03 m (7H, cyclohexane), 2.47 m (1H,
cyclohexane), 2.86 m (1H, ArCH), 3.21 s (1H, CH2),
3.22 s (1H, CH2), 4.21 q (2H, OCH2, J = 6.9 Hz),
6.05 s (1H, NH), 6.79 d (2H, 3′-H, 5′-H, J = 8.7 Hz),
7.13 d (2H, 2′-H, 6′-H, J = 8.7 Hz), 7.29 br.s (1H,
OH). Found, %: C 66.58; H 7.69; N 4.05. C18H25NO4·
0.5H2O. Calculated, %: C 66.03; H 7.94; N 4.28.
1. Glushkov, V.A., Stryapunina, O.G., Mayorova, O.A.,
Ryabukhina, S.Ya., Khorosheva, E.V., Gorbunov, A.A.,
Sokol, V.I., Slepukhin, P.A., and Shklyaev, Yu.V., Tetra-
hedron, 2010, vol. 66, p. 721.
2. Ausheva, O.G., Glushkov, V.A., and Shklyaev, Yu.V.,
Izv. Ross. Akad. Nauk, Ser. Khim., 2002, p. 822; Nifon-
tov, Yu.V., Glushkov, V.A., Ausheva, O.G., and Shklya-
ev, Yu.V., Russ. J. Org. Chem., 2002, vol. 38, p. 1386.
3
3
3
3. Plekhanova, I.V., Stryapunina, O.G., Glushkov, V.A.,
Karmanov, V.I., Maiorova, O.G., and Shklyaev, Yu.V.,
Russ. J. Org. Chem., 2009, vol. 45, p. 360.
4. Nifontov, Yu.V., Glushkov, V.A., and Shklyaev, Yu.V., Izv.
Ross. Akad. Nauk, Ser. Khim., 2003, p. 418.
5. Ausheva, O.G., Glushkov, V.A., and Shklyaev, Yu.V., Izv.
Ross. Akad. Nauk, Ser. Khim., 2002, p. 654.
6. Ausheva, O.G., Glushkov, V.A., Shurov, S.N., and
Shklyaev, Yu.V., Izv. Ross. Akad. Nauk, Ser. Khim., 2001,
p. 1571.
7. Glushkov, V.A., Ausheva, O.G., Anikina, L.V., Vikha-
rev, Yu.B., Safin, V.A., and Shklyaev, Yu.V., Khim.-Farm.
Zh., 2001, vol. 35, no. 7, p. 12.
8. Liang, B., Kalidindi, S., Porco, J.A., and Stephen-
son, C.R.J., Org. Lett., 2010, vol. 12, p. 572; Wei, Q. and
Gong, L.-Z., Org. Lett., 2010, vol. 12, p. 1008.
N-[2-(4-Hydroxyphenyl)-1-methylcyclohexyl]-
benzamide (V). Yield 48%, colorless crystals,
mp 102–104°C (decomp.; from hexane–CH2Cl2),
Rf 0.44. IR spectrum, ν, cm–1 (film): 3287 br (NH,
OH), 3015, 2975, 2930, 2856, 1650 (C=O), 1613
(C=C), 1578 w, 1514, 1486, 1443, 1372, 1314, 1273,
1235, 1177, 832, 756, 711. 1H NMR spectrum, δ, ppm:
1.36 s (3H, Me), 1.38–2.06 m (7H, cyclohexane),
2.61 m (1H, cyclohexane), 3.20 m (1H, ArCH), 5.49 s
(1H, NH), 6.09 br.s (1H, OH), 6.85 d (2H, 3′-H, 5′-H,
3
3J = 8.4 Hz), 7.13 d (2H, 2′-H, 6′-H, J = 8.4 Hz),
7.36–7.47 m (3H, 3-H, 4-H, 5-H), 7.65 d.d (2H, 2-H,
3
4
6-H, J = 8.4 Hz, J = 1.8 Hz). Found, %: C 77.35;
H 7.20; N 4.41. C20H23NO2. Calculated, %: C 77.64;
H 7.49; N 4.53.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 9 2011