Synthesis of substituted 5-N-(R)amino-4-cyclohexyl-1-ols by the reaction of secondary enaminones of β-dicarbonyl compounds with chalcones

Article abstract of DOI:10.1134/S1070363211100203

Reaction of secondary enaminones of acetylacetone or acetoacetic ester with chalcones at room temperature, is shown to lead to 5-N-(R)amino-4-cyclohexen-1- ols, distinctly to the reaction of the related primary derivatives leading to 1,4-dihydropyridines. Tertiary enaminones of identical structure are found not reacting with chalcones under the similar conditions. The reasons for the difference in the behavior of primary, secondary and tertiary enaminones in the reaction with chalcones are discussed. Pleiades Publishing, Ltd., 2011.

Full text of DOI:10.1134/S1070363211100203

ISSN 1070-3632, Russian Journal of General Chemistry, 2011, Vol. 81, No. 10, pp. 2157–2163. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © M.S. Sargsyan, S.S. Hayotsyan, A.Kh. Khachatryan, A.E. Badasyan, S.G. Kon’kova, 2011, published in Zhurnal Obshchei Khimii,
2011, Vol. 81, No. 10, pp. 1705–1711.
Synthesis of Substituted 5-N-(R)Amino-4-cyclohexyl-1-ols
by the Reaction of Secondary Enaminones
of β-Dicarbonyl Compounds with Chalcones
M. S. Sargsyan, S. S. Hayotsyan, A. Kh. Khachatryan, A. E. Badasyan, and S. G. Kon’kova
Institute of Organic Chemistry of the Scientific-Technological Center of Organic and Pharmaceutical Chemistry,
National Academy of Sciences of the Republic of Armenia,
pr. Azatutyana 26, Yerevan, 0014 Armenia
Received October 6, 2010
Abstract—Reaction of secondary enaminones of acetylacetone or acetoacetic ester with chalcones at room
temperature, is shown to lead to 5-N-(R)amino-4-cyclohexen-1-ols, distinctly to the reaction of the related
primary derivatives leading to 1,4-dihydropyridines. Tertiary enaminones of identical structure are found not
reacting with chalcones under the similar conditions. The reasons for the difference in the behavior of primary,
secondary and tertiary enaminones in the reaction with chalcones are discussed.
DOI: 10.1134/S1070363211100203
As is known, for the formation of substituted 1,4-
dihydropyridines III in the Hantzsch synthesis (R=H)
[1] is generally accepted a mechanism that includes
initial formation of α,β-unsaturated dicarbonyl
compound I (chalcone) and enaminone II, then their
addition, heterocyclization and water cleavage [2].
Among the evidences supporting such course of the
Hantzsch reaction is considered the fact that the
reaction of preliminary obtained chalcone I with
enaminone II also leads to the formation of 1,4-
dihydropyridines [3].
It is easy to see that under the conditions of the
Hantzsch reaction the intermediate imine IV can also
be a source of chalcone [4]. For the first time the
possibility of formation of the imine in the Hantzsch
R
N
O
O
O
O
O
+
NH2
R
+
R2
R1
R2
R1
IV
R
O
R
HN
O
R2
NH
O
R2
−RNH2
R1
O
R1
I
II
O
R1
O
R2
O
O
R2
O
R1
R1
R1
R1
−H2O
N
R
O
NH
R
III
2157

2158
SARGSYAN et al.
reaction was expressed in [4]. It was shown that
arylamines and related Schiff bases under the condi-
tions of the Hantzsch reaction afford the 1,4-dihydro-
pyridine derivatives III (R = Ar).
obtained from primary aminoalcohols [5] or in the
reaction of imines VI of the same aminoalcohol with
acetylacetone [6], as well as in the three-component
reaction of aldehyde, aminoalcohol and β-dicarbonyl
compound [7, 8] in alcohol at room temperature instead
of the expected N-substituted 1,4-dihydropyridines VII
(heterocyclization) are formed the corresponding
derivatives of 5-N-(ω-hydroxy)alkylamino-4-cyclo-
ohexen-1-ol VIII (carbocyclization).
The picture changes dramatically when in the
Hantzsch reaction and its modified versions are used
primary aminoalcohols. Recently, we have shown on
several examples that in the reaction of chalcone I with
either acetoacetic ester or acetylacetone enaminones V
O
R2
O
R1
R3
R
R1 = R3
O
O
HN
O
R
2
+
R2
N
VI
R1
HO
NH
R
R3
V
VIIIа−VIIIw
+
R1 = R3
R2
O
O
O
R2
O
R3
R1
O
O
+
NH2 +
R
R1
R2
O
R1
N
I
R
VII
To realize the reason for this difference, we
investigated in detail in the present study the reaction
of chalcone I with enaminones V. The experiments
showed that the direction of carbocyclization is of
general nature (see the table, VIIIa–VIIIp). In order to
ascertain whether the carbocyclization is caused by the
presence of the hydroxyl group in the enaminones V
[R = (CH2)nOH], it was replaced by a methoxy group.
It turned out that the direction of the reaction does not
change (see the table, VIIIq–VIIIs). Consequently, the
different behavior of the enaminones II and V is a
consequence of the fact that the hydrogen atom in the
enaminones II (R = H) is replaced by an alkyl group.
Based on the foregoing, we involved in this reaction
the enaminones V with a N-alkyl group. Experiments
showed that in this case occurs carbocyclization (see
the table, VIIIt–VIIIw).
Comparing the data obtained by us using primary
amines in two-component (enamine–chalcone, imine–
β-dicarbonyl compounds or tri-component (alkyl-
amine–aldehyde–β-dicarbonyl compound) syntheses of
the aminocyclohexenol derivatives with the data
obtained in the syntheses of the derivatives of 1,4-
dihydropyridines using ammonia, one can see that
structure of the intermediates that in one case lead to
aminocyclohexenols, while in other to 1,4-
dihydropyridines, is the same, because both these
reactions proceed via the formation of enaminone and
chalcone.
O
O
R2
R2
O
O
O
R
R3
R3
R1
R1
R2
HN
O
+
R3
R1
N
HN
R
O
O
O
R
IXA
IXB
I
V
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 81 No. 10 2011

SYNTHESIS OF SUBSTITUTED 5-N-(R)AMINO-4-CYCLOHEXYL-1-OLS
Yields and melting points of 5-N-(R)-amino-4-cyclohexene-1-ols
2159
Comp. no.
VIIIa
VIIIb
VIIIc
VIIId
VIIIe
VIIIf
R
(CH2)3OH
(CH2)2OH
(CH2)2OH
(CH2)3OH
(CH2)3OH
(CH2)3OH
(CH2)2OH
(CH2)2OH
(CH2)3OH
(CH2)2OH
C(CH3)2CH2OH
(CH2)2OH
(CH2)2OH
(CH2)2OH
(CH2)2OH
(CH2)2OH
(CH2)3OMe
(CH2)3OMe
(CH2)3OMe
Cy
R1
R2
R3
Yield, %
53
mp, °C
96 [7]
OEt
Ph
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
OEt
Me
OEt
OEt
OEt
OEt
Me
Me
Me
Me
Me
Me
Me
OEt
OEt
OEt
OEt
Me
Me
OEt
Me
Me
OEt
Me
4-ClC6H4
2-Furyl
2-Furyl
4-NO2C6H4
Ph
35.5
20
95–96
78
41
95
48
120
52.3
46.8
46
109
4-NO2C6H4
2-Furyl
Ph
158 [8]
145
VIIIg
VIIIh
VIIIi
73.9
54.3
51
155 [6]
160 [8]
178
4-NO2C6H4
Ph
VIIIj
VIIIk
VIIIl
2-(3,4,5-Trichlorothienyl)
45.5
41.5
27.8
41
161
Ph
115–116
116
VIIIm
VIIIn
VIIIo
VIIIp
VIIIq
VIIIr
VIIIs
VIIIt
4-ClC6H4
4-NO2C6H4
2-Furyl
Ph
135 [8]
123
45.5
64.2
43.3
28.3
45
107
4-ClC6H4
4-ClC6H4
Ph
130
111–112
145 [8]
Bn
Ph
63.6
36.7
68
165–166 [9]
74–75
VIIIu
VIIIv
VIIIw
Bn
Ph
Bn
2-Furyl
156
The question naturally arises, what is the cause of
the either regioselective cyclization (carbocyclization
involving the methyl group at the C=N bond) or
heterocyclization involving the nitrogen atom of the
intermediate compound IX. In our view, firstly, both
heterocyclization and carbocyclization proceed with
the participation of the imine tautomeric form IXA
only of intermediate IX, as the enamine tautomeric
form IXB being a vinylog of amide will have lower
nucleophilicity compared to the imine. In addition, we
showed in a separate experiment that the tertiary
enaminones which can not form imine, did not react
under similar conditions. Secondly, this difference is
not due to different nucleophilicity of nitrogen atom,
since otherwise the heterocyclization involving N-
alkylimino group theoretically would be more likely.
To understand the reason for the different behavior
of nitrogen in primary and secondary enaminones, we
supposed that in the intermediate compound, in the
case when R1 = R3= CH3, there are three nucleophilic
centers [two methyl groups (1, 3) and a nitrogen atom
(2)], the reactivity of two of them (2 and 3) is
somehow inhibited, or vice versa, some factors
contribute to increased reactivity of the methyl group
(1) associated with the C=N double bond.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 81 No. 10 2011

2160
SARGSYAN et al.
1
R2
O
R
O
R2
O
O
R2
O
R
3
3
N
2
2
O
N
1
O
N
O
O
3
1
2
R
R
N
O
R2
O
R2
N
O
O
R2
O
O
NH
R
OH
HO
R
X
XI
VIII
Such an assumption is quite reasonable, because
otherwise would have to react the theoretically more
reactive centers 2 or 3, to form X or XI, respectively.
A factor affecting the reactivity of CH3 group may be
the formation of intramolecular hydrogen bond in the
intermediate IX. In the case of ammonia the hydrogen
bond apparently involves the hydrogen atom of NH
group (XII), while in the case of N-substituted analogs
the nitrogen atom as shown by XIII, so that the
reactivity of methyl group 1 in the zwitter-ion XIV [9]
is enhanced, while of the remaining two (2 and 3), on
the contrary, is diminished.
3
3
O
O
O
R'
R'
R'
−O
O
O
H
H
+
HN2
R
N
N
2
O
O
O
1
1
R
XII
XIII
XIV
At this stage there is only one evidence of the
existence of an intramolecular hydrogen bond in the
intermediate: is the formation of aminocyclohexenols
(according to NMR COSY, NOESY, HMQC and
DEPT spectra) as a single stereoisomer.
crystals (1–10 days). Precipitated crystals were filtered
off, washed with absolute ether and recrystallized from
absolute ethanol. Attempted isolation of any com-
pound from the viscous mass remained after removing
the solvent, failed.
EXPERIMENTAL
3-(p-Chlorophenyl)-5-N-(2-hydroxyethyl)amino-
2,4-diethoxycarbonyl-1-methyl-4-cyclohexen-1-ol
(VIIIb). IR spectrum, ν, cm–1 : 3400–3200 (OH, NH),
1720 (COO), 1640, 1580, 710 (C=C–C=O and Ar). 1H
NMR spectrum, δ, ppm: 0.73 t (3H, Me, 4-CO2Et, J =
7.1 Hz), 1.07 t (3H, Me, 2-CO2Et, J = 7.1 Hz), 1.20 s
(3H, 1-CH3), 2.32 d (2-CH, J = 10.8 Hz), 2.45 d (1H,
J = 17.2 Hz) and 2.56 d (1H, 6-CH2, J = 17.2 Hz),
3.18–3.37 m (2H, NCH2), 3.52–3.59 m (2H, CH2OH),
3.62 d.q (1H, J = 7.1, 10.7 Hz) and 3.75 d.q (1H,
CH2CH3, 4-CO2Et, J = 7.1, 10.7 Hz), 3.88–4.01 m
(2H, CH2CH3, 2-CO2Et), 4.02 s (1H, 1-OH), 4.04 g
(1H, 3-CH, J = 10.4 Hz), 4.60 br (1H, CH2OH), 7.01–
7.15 m (4H, 4-ClC6H4), 9.04 t (1H, NH, J = 5.6 Hz).
1H NMR spectra of the synthesized compounds
were recorded on a Varian Mercury-300 instrument at
a frequency 300 MHz, at 303 K in DMSO-d6.
Chemical shifts are given relative to internal TMS. IR
spectra were recorded on a Specord 75 IR instrument
from the samples with vaseline oil, mass spectra on a
MX-1321 device with a direct inlet of the sample into
the ion source.
A general procedure for reacting enamnones V
with chalcone I. A solution of enaminone V and
chalcone I in absolute ethanol at a molar ratio 1:1 was
kept at room temperature until the end of dropping
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 81 No. 10 2011

SYNTHESIS OF SUBSTITUTED 5-N-(R)AMINO-4-CYCLOHEXYL-1-OLS
2161
3-(α-Furyl)-5-N-(2-hydroxyethyl)amino-2,4-di-
ethoxycarbnyl-1-methyl-4-cyclohexen-1-ol (VIIIc).
IR spectrum, ν, cm–1: 3400–3200 (OH, NH), 1730
3-Phenyl-5-N-(3-hydroxypropyl)amino-2-acetyl-
4-ethoxycarbonyl-1-methyl-4-cyclohexen-1-ol
(VIIIf). IR spectrum, ν, cm–1: 3400–3320 (OH, NH),
1690 (C=O), 1630, 1570, 780, 690 (C=C–C=O and
1
(COO), 1650, 1580, 710 (C=C–C=O), 1450 (Fu). H
1
NMR spectrum, δ, ppm: 0.94 t (3H, Me, 4-CO2Et, J =
7.1 Hz), 1.18 t (3H, Me, 2-CO2Et, J = 7.1 Hz), 1.19 s
(3H, 1-CH3), 2.36 d (1H, J = 17.0 Hz) and 2.58 d (1H,
6-CH2, J = 16.9 Hz), 2.59 d (1H, 2-CH, J = 9.2 Hz),
3.18–3.37 m (2H, NCH2), 3.57 q (2H, CH2OH, J =
5.4 Hz), 3.76 q.d (1H, J = 7.1, 10.7 Hz) and 3.92 q.d
(1H, CH2CH3, 4-CO2Et, J = 7.1, 10.7 Hz), 4.04 s (1H,
1-OH), 4.05 q (2H , CH2CH3, 2-CO2Et, J = 7.1 Hz),
4.21 d (1H, 3-CH, J = 9.1 Hz), 4.56 t (1H, CH2OH, J =
5.1 Hz), 5.79 d.t (1H, 3'-H, J = 3.7, 0.9 Hz) and 6.15
d.d (1H, 4'-H, J = 1.8, 3.1 Hz) and 7.20 d.d (1H, 5'-H,
α-Fu, J = 0.7, 1.8 Hz), 9.10 t (1H, NH, J = 5.6 Hz).
Ph). H NMR spectrum, δ, ppm: 0.66 t (3H, Me, 4-
CO2Et, J = 7.1 Hz), 1.17 s (3H, 1-CH3) 1.73 quintet
(2H, CH2CH2CH2, J = 6.6 Hz), 1.81 s (3H, 2-Ac), 2.42
d (1H, J = 17.5 Hz) and 2.56 d (1H, 6-CH2, J =
17.5 Hz), 2.58 d (1H, 2-CH, J = 10.6 Hz), 3.20–3.42 m
(2H, NCH2), 3.54 t (J = 5.8 Hz, 2H, CH2OH), 3.53–
3.79 m (2H, OCH2CH3), 3.95 d (1H, 3-CH, J =
11.1 Hz), 4.01 br.s (1H, 1-OH), 4.13–4.32 br.s (1H,
CH2OH), 6.99–7.21 m (5H, Ph), 8.92 t (1H, NH, J =
5.6 Hz).
3-(α-Furyl)-5-N-(2-hydroxyethyl)amino-2-acetyl-
4-ethoxycarbonyl-1-methyl-4-cyclohexen-1-ol (VIIIh).
IR spectrum, ν, cm–1 : 3400–3220 (OH, NH), 1710
3-(α-Furyl)-5-N-(3-hydroxypropyl)amino-2,4-di-
ethoxycarbnyl-1-methyl-4-cyclohexen-1-ol (VIIId).
IR spectrum, ν, cm–1: 3400–3200 (OH, NH), 1720
1
(C=O), 1650, 1580 (C=C–C=O), 1400 (Fu). H NMR
spectrum, δ, ppm: 0.94 t (3H, Me, 4-CO2Et, J =
7.1 Hz), 1.14 s (3H, 1-CH3), 2.7 s (3H, 2-Ac) , 2.35 d
(1H, J = 17.2 Hz) and 2.52 d (1H, 6-CH2, J = 17.2 Hz),
2.73 d (1H, 2-CH, J = 8.7 Hz), 3.20–3.34 m (2H,
NCH2), 3.57 q (2H, CH2OH, J = 5.5 Hz), 3.77 q.d (1H,
J = 7.1, 10.7 Hz) and 3.92 q.d (1H, OCH2CH3, J = 7.1,
10.7 Hz), 4.14 d (1H, 3-CH, J = 8.8 Hz), 4.25 s (1H, 1-
OH), 4.57 t (1H, CH2OH, J = 5.1 Hz), 5.79 t.d (1H,
3'-H, J = 0.6, 3.1 Hz) and 6.11 d.d (1H, 4'-H, J = 1.8,
3.1 Hz), and 7.22 d.d (1H, 5'-H, α-Fu, J = 0.9, 1.8 Hz),
9.09 t (J = 5.6 Hz, 1H, NH).
1
(COO), 1640, 1580, 710 (C=C–C=O), 1450 (Fu). H
NMR spectrum, δ, ppm: 0.94 t (3H, Me, 4-CO2Et, J =
7.1 Hz), 1.18 t (3H, Me, 2-CO2Et, J = 7.1 Hz), 1.19 s
(3H, 1-CH3), 1.71 quintet (2H, CH2CH2CH2, J =
6.6 Hz), 2.37 d (1H, J = 17.1 Hz) and 2.59 d (1H, 6-
CH2, J = 17.0 Hz), 2.59 d (1H 2-CH, J = 9.2 Hz), 3.20-
3.39 m (2H, NCH2), 3.53 q (2H, CH2OH, J = 5.4 Hz),
3.76 d.q ( 1H, J = 10.7, 7.1 Hz) and 3.92 d.q (1H,
CH2CH3, 4-CO2Et, J = 10.7, 7.1 Hz), 4.03 s (1H, 1-
OH), 4.06 q (2H, CH2CH3, 2-CO2Et, J = 7.1 Hz), 4.19
d (1H, 3-CH, J = 9.1 Hz), 4.22 t (1H, CH2OH, J =
5.0 Hz), 5.78 d.t (1H, 3'-H, J = 3.3, 0.7 Hz) and 6.15
d.d (1H, 4'-H, J = 3.2, 1.9 Hz), and 7.20 d.d (1H, 5'-H,
α-Fu, J = 1.9, 0.8 Hz), 8.99 t (1H, NH, J = 5.6 Hz).
3-Phenyl-5-N-(1,1-dimethyl-2-hydroxyethyl)amino-
2,4-diacetyl-1-methyl-4-cyclohexene-1-ol (VIIIk). IR
spectrum, ν, cm–1: 3290 (OH), 3200 (NH), 1680
1
(C=O), 1590, 1510 (C=C–C=O), 760, 690 (Ph). H
NMR spectrum, δ, ppm: 1.08 s (3H, 1-CH3), 1.24 s
(3H) and 1.32 s (3H, (CH3)2C), 1.67 c (3H, 4-Ac) ,
1.77 d (1H, J = 13.4 Hz) and 1.89 d (1-H, 6-CH2, J =
13.3 Hz), 1.91 s (3H, 2-Ac), 2.74 d (1H, 2-CH, J =
10.8 Hz), 3.22 d (1H, J = 8.1 Hz) and 3.59 d (1H,
CH2OH, J = 8.1 Hz), 3.33 d.d (1H, CH2OH, J = 17.8,
7.0 Hz), 3.38 d (1H, 3-CH, J = 10.9 Hz), 4.06 s (1H, 1-
OH), 6.86 s (1H, NH), 7.11–7.28 m (5H, Ph).
3-(p-Nitrophenyl)-5-N-(3-hydroxypropyl)amino-
2,4-diethoxycarbnyl-1-methyl-4-cyclohexen-1-ol
(VIIIe). IR spectrum, ν, cm–1: 3430 (OH), 3290 (NH),
1730 (COO), 1630, 1590, 1520, 860, 840 (C=C–C=O
and Ar). 1H NMR spectrum, δ, ppm: 0.71 t (3H, Me, 4-
CO2Et, J = 7.1 Hz), 1.07 t (3H, Me, 2-CO2Et, J =
7.1 Hz), 1.23 s (3H, 1-CH3), 1.73 quintet (2H,
CH2CH2CH2, J = 6.5 Hz), 2.36 d (1H, 2-CH, J =
11.0 Hz), 2.51 d (1H, J = 17.2 Hz) and 2.63 d (1H, 6-
CH2, J = 17.4 Hz), 3.33 d.q (2H, NCH2, J = 12.9,
6.1 Hz), 3.55 d.d (2H, CH2OH, J = 11.1, 5.9 Hz),
3.58–3.77 m (2H, CH2CH3, 4-CO2Et), 3.85–4.05 m
(2H, CH2CH3, 2-CO2Et), 4.14 s (1H, 1-OH), 4.21 d
(1H, 3-CH, J = 11.0 Hz), 4.26 t (1H, CH2OH , J =
5.0 Hz), 7.28–7.34 m (2H) and 7.98–8.05 m (2H, 4-
NO2 C6H4), 9.04 t (1H, NH, J = 5.5 Hz).
3-(1,2,3-Trichloro)thienyl-5-N-(2-hydroxyethyl)-
amino-2,4-diacetyl-1-methyl-4-cyclohexen-1-ol (VIIIl).
IR spectrum, ν, cm–1: 3400–3200 (OH, NH), 1690
(C=O), 1580, 1540 (C=C–C=O). 1H NMR spectrum, δ,
ppm: 1.25 s (3H, 1-CH3), 1.80 s (3H, 4-Ac), 2.24 s
(3H, 2-Ac), 2.41 d (1H, J = 16.8 Hz) and 2.62 d (1H,
6-CH2, J = 16.8 Hz), 2.78 d (2-CH, J = 6.7 Hz), 3.25–
3.43 m (2H, CH2N), 3.59 q (2H, CH2OH, J = 5.4 Hz),
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2162
SARGSYAN et al.
4.55 d ( 1H, 3-CH, J = 6.7 Hz), 4.58 s (1H, 1-OH),
4.69 t (1H, CH2OH, J = 5.0 Hz), 11.59 t (1H, NH, J =
5.6 Hz) . Mass spectrum, m/e: 439, 441 [M]+.
J = 12.2, 6.1 Hz), 1.86 s (3H, 2-Ac), 2.42 d (1H, J =
17.4 Hz) and 2.55 d (1H, 6-CH2, J = 17.4 Hz), 2.60 d
(1H, 2-CH, J = 10.2 Hz), 3.31 s (3H, MeO), 3.31 d.q
(2H, NCH2, J = 13.2, 6.5 Hz), 3.44 t (2H, CH2O, J =
6.0 Hz), br.s 3.90–4.26 (1H, 1-OH), 4.10 d (1H, 3-CH,
J = 10.0 Hz), 7.00–7.27 m (5H, Ph), 11.43 t (1H, NH,
J = 5.6 Hz).
3-Phenyl-5-N-(2-hydroxyethyl)amino-2-ethoxy-
carbonyl-4-acetyl-1-methyl-4-cyclohexen-1-ol (VIIIo).
IR spectrum, ν, cm–1: 3320 (OH ), 3150 (NH), 1720
1
(COO), 1580, 1510, 750, 700 (C=C-C=O and Ph). H
NMR spectrum, δ, ppm: 1.07 t (3H, Me, 2-CO2Et, J =
7.1 Hz), 1.20 s (3H, 1-CH3), 1.53 s (3H, 4-Ac) , 2.36 d
(1H, 2-CH, J = 10.3 Hz), 2.45 d (1H, J = 17.3 Hz) and
2.63 d (1H, 6-CH2, J = 17.4 Hz), 3.24–3.39 m (2H,
NCH2), 3.60 q (2H, CH2OH, J = 5.5 Hz), 3.98 q.d (2H,
OCH2CH3, J = 7.1, 1.3 Hz), 4.4 s (1H, 1-OH), 4.20 d
(1H, 3-CH, J = 10.2 Hz), 4.62 t (1H, CH2OH, J =
5.2 Hz), 7.05–7.12 m (3H) and 7.14–7.22 m (2H, Ph),
11.42 t (1H, NH, J = 5.6 Hz).
3-(p-Chlorophenyl)-5-N-(3-methoxypropyl)amino-
2,4-diacetyl-1-methyl-4-cyclohexen-1-ol (VIIIr). IR
spectrum, ν, cm–1: 3400–3150 (OH, NH), 1700 (C=O),
1590, 1540, 860, 810 (C=C–C=O and Ar), 1200, 1100
1
(COC). H NMR spectrum, δ, ppm : 1.16 s (3H, 1-
CH3), 1.53
s (3H, 4-Ac), 1.77–1.88 m (2H,
CH2CH2CH2), 1.92 s (3H, 2-Ac), 2.43 d (1H, J =
17.2 Hz) and 2.56 d (1H, 6-CH2, J = 17.4 Hz), 2.54 d
(1H, 2-CH, J = 10.0 Hz), 3.21–3.39 m (2H, NCH2),
3.32 s (3H, MeO), 3.44 t (2H, CH2O, J = 6.0 Hz),
4.00–4.30 br.s (1H, 1-OH), 4.13 d (1H, 3-CH, J =
10.0 Hz), 7.03–7.08 m (2H) and 7.16–7.22 m (2H, 4-
ClC6H4), 11.45 t (1H, NH, J = 5.6 Hz).
3-(p-Chlorophenyl)-5-N-(2-hydroxyethyl)amino-
2-ethoxycarbonyl-4-acetyl-1-methyl-4-cyclohexen-
1-ol (VIIIn). IR spectrum, ν, cm–1 : 3400–3200 (OH,
NH), 1720 (COO), 1590, 1530, 860, 810 (C=C–C=O
and Ar). 1H NMR spectrum, δ, ppm: 1.12 t (3H, Me, 2-
CO2Et, J = 7.1 Hz), 1.20 s (3H, 1-CH3), 1.54 s (3H, 4-
Ac) , 2.32 d (1H, 2-CH, J = 10.3 Hz), 2.46 d (1H, J =
17.1 Hz) and 2.62 d (1H, 6-CH2, J = 17.4 Hz), 3.23–
3.41 m (2H, NCH2), 3.59 d.d (2H, CH2OH, J = 5.1,
9.8 Hz), 3.93–4.06 m (2H, OCH2CH3), 4.11 br.s (1H,
1-OH), 4.21 d (1H 3-CH, J = 10.3 Hz), 4.61 t (1H,
CH2OH, J = 5.2 Hz), 7.06–7.21 m (4H, 4-ClC6H4),
11.43 t (1H, NH, J = 5.7 Hz).
3-(p-Chlorophenyl)-5-N-(3-methoxypropyl)amino-
2-ethoxycarbonyl-4-acetyl-1-methyl-4-cyclohexen-
1-ol (VIIIs). IR spectrum, ν, cm–1: 3400–3200 (OH,
NH), 1720 (COO), 1590, 1540, 860, 810 (C=C–C=O
1
and Ar), 1190, 1110 (COC). H NMR , δ, ppm: 1.10 t
(3H, Me, 2-CO2Et, J = 7.1 Hz), 1.19 s (3H, 1-CH3),
1.52 s (3H, 4-Ac), 1.76–1.87 m (2H, CH2CH2CH2),
2.31 d (1H, 2-CH, J = 10.4 Hz), 2.44 d (1H, J =
17.1 Hz) and 2.59 d (1H, 6-CH2, J = 17.4 Hz), 3.31 s
(3H, MeO), 3.31 d.t.d (2H, NCH2, J = 16.5, 9.4,
6.9 Hz), 3.43 t (2H, CH2O, J = 5.9 Hz), 3.98 q.d.d
( 2H, OCH2CH3, J = 14.1, 9.0, 5.3 Hz), 4.06–4.25 br.s
(1H, 1-OH), 4.19 d (1H, 3-CH, J = 10.3 Hz), 7.02–
7.12 m (2H) and 7.13–7.22 m (2H, 4-ClC6H4), 11.42 t
(1H, NH, J = 5.5 Hz).
3-(α-Furyl)-5-N-(2-hydroxyethyl)amino-2-ethoxy-
carbonyl-4-acetyl-1-methyl-4-cyclohexene-1-ol (VIIIp).
IR spectrum, ν, cm–1: 3400–3340 (OH), 3120 (NH),
1
1720 (COO), 1590, 1530 (C=C–C=O), 1450 (Fu). H
NMR spectrum, δ, ppm: 1.21 t (3H, Me, 2-CO2Et, J =
7.1 Hz), 1.22 s (3H, 1-CH3), 1.76 s (3H, 4-Ac) , 2.36 d
(1H, J = 16.7 Hz) and 2.63 d (1H, 6-CH2, J = 16.8 Hz),
2.68 d (1H, 2-CH, J = 7.6 Hz), 3.24-3.40 m (2H,
NCH2), 3.58 t (2H, CH2OH, J = 5.5 Hz), 4.09 q (2H,
OCH2CH3, J = 7.1 Hz), 4.19 br.s (1H, 1-OH), 4.33 d
(1H, 3-CH, J = 7.6 Hz), 4.65 br.s (1H, CH2OH), 5.88
d.t (1H, 3'- H, J = 3.5, 0.9 Hz) and 6.20 d.d (1H, 4'-H,
J = 3.2, 1.8 Hz), and 7.29 d.d (1H, 5'-H, α-Fu, J = 1.9,
0.9 Hz), 11.49 t (1H, NH, J = 5.8 Hz).
3-Phenyl-5-N-benzylamino-2,4-diethoxycarbnyl-
1-methyl-4-cyclohexen-1-ol (VIIIv). IR spectrum, ν,
cm–1: 3350–3200 (OH, NH), 1720 (COO), 1690, 750,
1
710 (C=C–C=O and Ar); H NMR spectrum, δ, ppm:
0.67 t (3H, CH3, 2-CO2Et J = 7.1 Hz), 0.87 t (CH3, 4-
CO2Et, J = 7.1 Hz), 1.17 s (3H, 1-CH3), 2.35 d (1H, 2-
CH, J = 10.7 Hz), 2.38 d (J = 17.3 Hz , 1H) and 2.58 d
(1H, 6-CH2, J = 17.2 Hz), 3.61 d.q (1H, J = 10.8,
7.1 Hz) and 3.75 d.q (1H, CH2, 4-CO2Et, J = 10.8,
7.1 Hz,), 3.89 s (1H, 1-OH), 3.93 d.d (2H, CH2, 2-
CO2Et, J = 14.3, 7.2 Hz), 4.05 d (1H, 3-CH, J = 10.8
Hz), 4.44–4.50 m (2H, NCH2), 6.99–7.40 m (10H,
2Ph), 9.28 t (1H, NH, J = 6.0 Hz).
3-Phenyl-5-N-(3-methoxypropyl)amino-2,4-di-
acetyl-1-methyl-4-cyclohexen-1-ol (VIIIq). IR spec-
trum, ν, cm–1: 3400–3200 (OH, NH), 1700 (C=O),
1590, 1540, 750, 710 (C=C–C=O and Ar), 1190–1110
(COC). 1H NMR spectrum, δ, ppm: 1.15 s (3H,
1-CH3), 1.52 s (3H, 4-Ac), 1.81 d.d (2H, CH2CH2CH2,
3-(α-Furyl)-5-N-benzylamino-2,4-diacetyl-1-methyl-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 81 No. 10 2011

SYNTHESIS OF SUBSTITUTED 5-N-(R)AMINO-4-CYCLOHEXYL-1-OLS
2163
4-cyclohexen-1-ol (VIIIw). IR spectrum, ν, cm–1:
3. Phillips, A.P., J. Am. Chem. Soc., 1951, vol. 73, p. 2248.
3400–3150 (OH, NH), 1710 (C=O), 1590, 790, 710
(C=C–C=O and Ar), 1460 (Fu). H NMR spectrum, δ,
4. Sausin’, A.E., Chekavichus, B.S., Lusis, V.K., and
Dubur, G.Ya., Khim. Geterotsikl. Soedin., 1980, no. 4,
p. 493.
1
ppm: 1.13 s (3H, 1-CH3), 1.78 s (3H, 4-Ac), 2.14 s
(3H, 2-Ac), 2.35 d (1H, J = 16.9 Hz) and 2.55 d (1H,
6-CH2, J = 17.0 Hz), 2.86 d (1H, 2-CH, J = 7.4 Hz),
4.25 d (1H, 3-CH, J = 7.5 Hz), 4.37 s (1H, 1-OH), 4.49
d (2H, CH2N, J = 5.9 Hz), 5.91 t.d (1H, 3'-H, J = 0.8,
3.5 Hz) and 6.23 d.d (1H, 4'-H, J = 1.8, 3.2 Hz) and
7.21–7.38 m (6H, 5'-H, α-Fu and the 5H, Ph), 11.76 t
(1H, NH, J = 5.9 Hz).
5. Kon’kova, S.G., Aiotsyan, S.S., Khachatryan, A.Kh.,
Badasyan, A.E., and Sargsyan, M.S., Zh. Obshch.
Khim., 2008, vol. 78, no. 4, p. 698.
6. Sargsyan, M.S., Aiotsyan, S.S., Khachatryan, A.Kh.,
Badasyan, A.E., and Kon’kova, S.G., Khim. Zh. Arm.,
2009, vol. 62, nos. 3–4, p. 392.
7. Sargsyan, M.S., Aiotsyan, S.S., Khachatryan, A.Kh.,
Badasyan, A.E., Panosyan, G.A., and Kon’kova, S.G.,
Zh. Obshch. Khim., 2009, vol. 79, no. 5, p. 866.
REFERENCES
8. Sargsyan, M.S., Aiotsyan, S.S., Khachatryan, A.Kh.,
Badasyan, A.E., and Kon’kova, S.G., Khim. Zh. Arm.,
2008, vol. 61, nos. 3–4, p. 504.
1. Hantzsch, A., Lieb. Ann., 1882, vol. 215, no. 1, p. 1.
2. Katritzky, A.R., Ostercamp, D.L., and Yousaf, T.I.,
Tetrahedron, 1987, vol. 43, p. 5171.
9. Greenhill, J.V., Chem. Soc. Rev., 1977, vol. 6, p. 277.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 81 No. 10 2011