Synthesis of exo- and endocyclic enamino derivatives of 2-(3-arylprop-2-enoyl)cyclohexane-1,3-diones

Article abstract of DOI:10.1134/S1070428011030018

Condensation of 2-acetylcyclohexane-1,3-diones with aromatic aldehydes in the presence of piperidine, pyrrolidine, hexamethyleneimine, or morpholine gave the corresponding 2-(3-arylprop-2-enoyl)cyclohexane-1,3-diones as the major products and 2-[3-aryl-1-cycloalkylaminoprop-2-en-1-ylidene]cyclohexane-1,3- diones as minor ones. Endocyclic enamino derivatives were synthesized in two steps through enol methyl ethers which reacted with amines. Endocyclic enamino derivatives of 2-(3-arylprop-2-enoyl)cyclohexane-1,3-diones containing an aryl group on the nitrogen atom readily underwent cyclization to 1,2,3,4,5,6,7,8- octahydroquinoline-4,5-dione derivatives.

Full text of DOI:10.1134/S1070428011030018

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 3, pp. 319–330. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © D.B. Rubinov, I.L. Rubinova, F.A. Lakhvich, 2011, published in Zhurnal Organicheskoi Khimii, 2011, Vol. 47, No. 3, pp. 327–338.
Synthesis of Exo- and Endocyclic Enamino Derivatives
of 2-(3-Arylprop-2-enoyl)cyclohexane-1,3-diones
D. B. Rubinov, I. L. Rubinova, and F. A. Lakhvich
Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus,
ul. Akademika Kuprevicha 5/2, Minsk, 220141 Belarus
e-mail: rub_irin@mail.ru
Received January 18, 2010
Abstract—Condensation of 2-acetylcyclohexane-1,3-diones with aromatic aldehydes in the presence of piperi-
dine, pyrrolidine, hexamethyleneimine, or morpholine gave the corresponding 2-(3-arylprop-2-enoyl)cyclo-
hexane-1,3-diones as the major products and 2-[3-aryl-1-cycloalkylaminoprop-2-en-1-ylidene]cyclohexane-
1,3-diones as minor ones. Endocyclic enamino derivatives were synthesized in two steps through enol methyl
ethers which reacted with amines. Endocyclic enamino derivatives of 2-(3-arylprop-2-enoyl)cyclohexane-1,3-
diones containing an aryl group on the nitrogen atom readily underwent cyclization to 1,2,3,4,5,6,7,8-octa-
hydroquinoline-4,5-dione derivatives.
DOI: 10.1134/S1070428011030018
Many natural alicyclic β-triketones contain a side-
chain 3-arylprop-2-enoyl fragment [1, 2]. Such com-
pounds are generally synthesized by condensation of
appropriately substituted 2-acetylcycloalkane-1,3-di-
ones like I with aromatic aldehydes in the presence of
piperidine as base catalyst. Analogous reaction is
known for some heterocyclic β-tricarbonyl com-
pounds, e.g., 3-acetyltetronic acid [3], 3-acetyltetramic
acid [4, 5], and dehydroacetic acid [6, 7].
hyde, 3,4-dimethoxybenzaldehyde, 2,4,6-trimethyl-
benzaldehyde, 4-hydroxybenzaldehyde, and 1,3-benzo-
dioxole-5-carbaldehyde), and cyclic secondary amines
(pyrrolidine, piperidine, morpholine, and hexameth-
yleneimine) to synthesize a series of 2-(3-arylprop-2-
enoyl)cyclohexane-1,3-diones IIa–IIf.
Detailed study on the condensation of 2-acetyl-
cyclohexane-1,3-diones Ia and Ib with aromatic alde-
hydes showed that, regardless of the secondary amine
used as catalyst, exocyclic enaminodiketones IIIa–IIIg
were always formed (yield 10–20%) in addition to
target triketones IIa–IIf (Scheme 1). Our attempts to
obtain compounds IIIc, IIIf, and IIIg by reaction of
triketones IIb, IIc, and IIe, respectively, with piper-
idine or pyrrolidine were unsuccessful. Prolonged
heating of the reaction mixture resulted in tarring.
Such behavior of triketones IIb, IIc, and IIe toward
secondary amines is analogous to the behavior of
2-acylcyclohexane-1,3-diones with a saturated side
chain; the latter gave rise to products with tertiary
amino group only in the reaction with pyrrolidine [15].
Preliminary transformation of triketone Ib into the
corresponding pyrrolidine enamine and its subsequent
reaction with 4-methoxybenzaldehyde did not lead to
the formation of enaminodiketone IIIf.
High regioselectivity of the reaction of aromatic
aldehyde at the β-triketone fragment and preparative
yields of the target products have determined wide
application of this procedure in various syntheses of
prostaglandin analogs [8, 9]. An exception from the
above series was 3-acetylthiotetronic acid which re-
acted with aromatic aldehydes under the conditions of
both basic and acid catalysis at the endocyclic meth-
ylene group [10]. In the presence of excess aldehyde
the condensation involved both reaction centers [11].
Enamino derivatives of 2-acylcyclohexane-1,3-di-
ones with a saturated aliphatic chain in the acyl frag-
ment showed pesticidal activity [12–14]. There are no
published data on the synthesis and biological activity
of exo- and endocyclic enamino derivatives of
2-(3-arylprop-2-enoyl)cyclohexane-1,3-diones. We
used 2-acetyl-5,5-dimethylcyclohexane-1,3-dione (Ia)
and 2-acetyl-5-mesitylcyclohexane-1,3-dione (Ib), aro-
matic aldehydes (benzaldehyde, 4-methoxybenzalde-
1
Analysis of the H NMR spectra of triketones IIa–
IIf having a conjugated oxo group in the side chain
showed that these compounds, as well as 2-acylcyclo-
319

RUBINOV et al.
320
Scheme 1.
O
O
O
O
O
O
NR3R4
ArCHO, HNR3R4
Me
Ar
Ar
+
R1
R2
R1
R2
R1
R2
O
O
IIIa–IIIk
Ia, Ib
IIa–IIf
I, R1 = R2 = Me (a); R1 = H, R2 = 2,4,6-Me3C6H2 (b); II, R1 = R2 = Me, Ar = Ph (a), 4-MeOC6H4 (b), 3,4-(MeO)2C6H3 (c),
2,4,6-Me3C6H2 (d); R1 = H, R2 = 2,4,6-Me3C6H2, Ar = 4-MeOC6H4 (e), 3,4-(OCH2O)C6H3 (f); III, R1 = R2 = Me, R3R4 = (CH2)6,
Ar = Ph (a); R1 = R2 = Me, R3R4 = (CH2)2O(CH2)2, Ar = 4-MeOC6H4 (b); R1 = R2 = Me, R3R4 = (CH2)5, Ar = 4-MeOC6H4 (c); R1 =
R2 = Me, R3R4 = (CH2)5, Ar = 3,4-(MeO)2C6H3 (d); R1 = R2 = Me, R3R4 = (CH2)6, Ar = 2,4,6-Me3C6H2 (e); R1 = H, R2 =
2,4,6-Me3C6H2, R3R4 = (CH2)4, Ar = 4-MeOC6H4 (f); R1 = H, R2 = 2,4,6-Me3C6H2, R3R4 = (CH2)5, Ar = 3,4-(OCH2O)C6H3 (g);
R1 = R2 = Me, R3 = 4-MeOC6H4CH2, R4 = H, Ar = Ph (h); R1 = R2 = Me, R3 = i-Pr, R4 = H, Ar = 4-MeOC6H4 (i); R1 = R2 = Me,
R3 = PhCH2, R4 = H, Ar = 4-MeOC6H4 (j); R1 = R4 = H, R2 = 2,4,6-Me3C6H2, R3 = 4-MeOC6H4CH2, Ar = 3,4-(OCH2O)C6H3 (k).
hexane-1,3-diones with a saturated aliphatic side chain,
are completely enolized. The spectra contained a down-
field signal at δ 18.4–18.6 ppm due to intermolecularly
chelated proton. Such signal is typical of all cyclic
β-triketones, and it appears in a weaker field (by 0.2–
0.3 ppm) relative to the corresponding signal of β-tri-
ketones I with a saturated acyl side chain [16, 17],
indicating stronger intramolecular hydrogen bond in
2-(3-arylprop-2-enoyl)cyclohexane-1,3-diones IIa–IIf.
absorption band was very sensitive to conjugation
parameters, and its frequency was lower by 20–30 cm–1
as compared to analogous absorption band in the spec-
tra of 2-alkanoylcyclohexane-1,3-diones [16, 17].
The position of the enamine fragment in molecules
IIIa–IIIg was confirmed by the NMR data. Carbon
atoms in the methylene and carbonyl groups in the six-
membered ring were magnetically equivalent in pairs.
In the 1H NMR spectra of IIIa–IIIe methylene protons
in the cyclohexane-1,3-dione fragment appeared as
a broadened singlet with an intensity of 4H. The IR
spectra of IIIa–IIIg contained strong absorption bands
at 1555 and 1565 cm–1, which were assigned to stretch-
ing vibrations of the s-trans- and s-cis-conjugated
endocyclic carbonyl groups, respectively; in addition,
a broadened band was observed at 1520–1530 cm–1
due to vibrations of the conjugated double bond.
Compounds IIa–IIf displayed in the IR spectra
strong absorption bands belonging to stretching vibra-
tions of the conjugated endocyclic carbonyl group
(1660–1665 cm–1), conjugated double C=C bond in the
acyl side chain (1620–1625 cm–1), side-chain carbonyl
group involved in intramolecular hydrogen bond
(1570–1580 cm–1), and conjugated endocyclic double
C=C bond (1520–1530 cm–1). The position of the latter
Scheme 2.
O
O
O
O
O
O
Me2SO4
K2CO3
R4 = H
HNR3R4
Ar
Ar
IIa, IIb, IIf
R1
R2
R1
R2
R1
R2
OMe
NR3R4
N
Ar
R3
IVa–IVc
Va–Vp
VIa–VIg
IV, R1 = R2 = Me, Ar = Ph (a), 4-MeOC6H4 (b); R1 = H, R2 = 2,4,6-Me3C6H2, Ar = 3,4-(OCH2O)C6H3 (c); V, R1 = R2 = Me, R3 =
3,4-Me2C6H3, R4 = H, Ar = Ph (a); R1 = R2 = Me, R3 = 4-MeOC6H4, R4 = H, Ar = Ph (b); R1 = R2 = R3 = Me, R4 = H, Ar =
4-MeOC6H4 (c); R1 = R2 = Me, R3 = i-Pr, R4 = H, Ar = 4-MeOC6H4 (d); R1 = R2 = Me, R3 = PhCH2, R4 = H, Ar = 4-MeOC6H4 (e);
R1 = R2 = Me, R3 = 4-MeC6H4CH2, R4 = H, Ar = 4-MeOC6H4 (f); R1 = R2 = Me, R3 = 4-MeOC6H4CH2, R4 = H, Ar =
4-MeOC6H4 (g); R1 = R2 = Me, R3 = 3,4-Me2C6H3, R4 = H, Ar = 4-MeOC6H4 (h); R1 = R2 = Me, R3 = 4-MeC6H4, R4 = H, Ar =
4-MeOC6H4 (i); R1 = R2 = Me, R3 = Ar = 4-MeOC6H4, R4 = H (j); R1 = R4 = H, R2 = 2,4,6-Me3C6H2, R3 = CH2=CHCH2, Ar =
3,4-(OCH2O)C6H3 (k); R1 = R4 = H, R2 = 2,4,6-Me3C6H2, R3 = 4-MeOC6H4CH2, Ar = 3,4-(OCH2O)C6H3 (l); R1 = R4 = H, R2 =
2,4,6-Me3C6H2, R3 = 4-MeOC6H4, Ar = 3,4-(OCH2O)C6H3 (m); R1 = R4 = H, R2 = 2,4,6-Me3C6H2, R3 = 4-MeC6H4, Ar =
3,4-(OCH2O)C6H3 (n); R1 = R2 = Me, R3R4 = (CH2)5, Ar = 4-MeOC6H4 (o); R1 = H, R2 = 2,4,6-Me3C6H2, R3R4 = (CH2)5, Ar =
3,4-(OCH2O)C6H3 (p); VI, R1 = R2 = Me, R3 = 4-MeOC6H4, Ar = Ph (a); R1 = R2 = Me, R3 = 3,4-(Me)2C6H3, Ar = Ph (b); R1 = R2 =
Me, R3 = 4-MeC6H4, Ar = 4-MeOC6H4 (c); R1 = R2 = Me, R3 = 3,4-Me2C6H3, Ar = 4-MeOC6H4 (d); R1 = R2 = Me, R3 = Ar =
4-MeOC6H4 (c); R1 = H, R2 = 2,4,6-Me3C6H2, R3 = 4-MeOC6H4, Ar = 3,4-(OCH2O)C6H3 (f); R1 = H, R2 = 2,4,6-Me3C6H2, R3 =
4-MeC6H4, Ar = 3,4-(OCH2O)C6H3 (g).
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SYNTHESIS OF EXO- AND ENDOCYCLIC ENAMINO DERIVATIVES
321
Reactions of piperidine derivatives IIIc, IIId, and
IIIg with primary aliphatic amines (isopropylamine,
benzylamine, and 4-methoxybenzylamine) afforded
70–75% of the corresponding transamination products
IIIh–IIIk. The same compounds were also obtained
(though in lower yield) by heating triketones IIa, IIb,
and IIf with the above amines in boiling toluene.
Reactions of both triketones IIa, IIb, and IIf and
enaminodiketones IIIc, IIId, and IIIg with aromatic
amines (p-toluidine and p-anisidine) led to the forma-
tion of complex mixtures of products which were not
isolated and identified. The structure of compounds
IIIh–IIIk was assigned on the basis of the same
parameters as for IIIa–IIIg.
hydrogen bond. The coupling constant between the NH
proton and methylene protons in the N-alkyl substit-
uent in enamines Vc–Vg, Vk, and Vl was equal to 6.0–
6.5 Hz. The IR spectra of Va–Vn in the carbonyl
region were analogous to the spectra of enaminodi-
ketones having an alkyl substituent in the side chain
[12]. Compounds Va–Vn displayed one or two very
strong absorption bands at 1550–1580 cm–1 due to
endocyclic enaminoketone system, and the side-chain
carbonyl group was characterized by medium-intensity
absorption at 1630–1640 cm–1 (H-chelate ring).
The chemical behavior of enaminodiketones Va–
Vn strongly depended on the nature of substituent (ali-
phatic or aromatic) on the nitrogen atom. Compounds
Vc–Vg, Vk, and Vl having an aliphatic substituent on
the nitrogen remained unchanged upon heating in
boiling toluene over a period of 40 h. Under analogous
conditions aromatic enamines Va, Vb, Vh, Vi, Vm,
and Vn in 6–8 h underwent cyclization by 80–90%
(TLC) to the corresponding octahydroquinoline deriv-
atives VIa–VIg. This transformation is reversible, and
it may be regarded as a version of ring–chain tautom-
erism. 7,7-Dimethylquinolines VIa–VIe crystallized
from the reaction mixture as individual substances;
whereas crystals of initial enaminodiketones Vm and
Vn separated from the equilibrium toluene solution
containing compounds VIf and VIg. The latter were
isolated from the equilibrium mixture by column
chromatography.
Transformation of cyclic β-tricarbonyl compounds
into enol methyl ethers changes the direction of nu-
cleophilic attack in their reactions with amines so that
endocyclic enamino derivatives could be obtained
[15]. Alkylation of triketones IIa, IIb, and IIf with
dimethyl sulfate in the presence of anhydrous potas-
sium carbonate [18] gave methyl ethers IVa–IVc in
75–80% yield (Scheme 2).
In the IR spectra of enol ethers IVa–IVc we ob-
served strong absorption bands due to conjugated
endocyclic carbonyl group at 1630–1640 cm–1, con-
jugated double C=C bonds at 1580–1630 cm–1, and
conjugated exocyclic carbonyl group at 1660–
1665 cm–1. Methyl ethers derived from enolized
2-acylcyclohexane-1,3-diones are characterized by
analogous absorption bands, except for that corre-
sponding to the side-chain carbonyl group; the latter
gives rise to absorption at 1705–1710 cm–1 [18].
Octahydroquinoline-4,5-diones VIa, VIc, VId, VIf,
1
and VIg showed in the H NMR spectra broadened
signals from protons in the symmetric aromatic system
on the nitrogen atom due to their nonequivalence. The
IR spectra of VIa–VIg contained strong absorption
bands corresponding to the s-cis-conjugated carbonyl
group at 1670–1680 cm–1 and very strong absorption
bands belonging to the s-trans-conjugated carbonyl
group (together with the conjugated double C=C bond
and aromatic C–C bonds) at 1490–1525 cm–1.
The presence of conjugated double C=C bonds in
both cyclic and side-chain fragments of compounds
IVa–IVc implies two possible directions of nucleo-
philic attack in their reactions with amines. However,
methyl ethers IVa–IVc reacted with aliphatic and
aromatic amines to produce only endocyclic enamino
derivatives Va–Vn in 90–95% yield. In the reactions of
ethers IVb and IVc with piperidine we isolated
enamines Vo and Vp whose chromatographic and
spectral properties differed from those of regioisomeric
exocyclic enamino derivatives IIIc and IIIg; this was
interpreted as an additional evidence in favor of the
assumed structure of enaminodiketones III.
Thus 2-(3-arylprop-2-enoyl)cyclohexane-1,3-di-
ones obtained by condensation of 2-acetylcyclo-
hexane-1,3-diones with aromatic aldehydes can be con-
verted into endocyclic arylamino derivatives through
the corresponding enol methyl ethers. The resulting
enamines undergo intramolecular cyclization to form
in good yields substituted octahydroquinoline-4,5-di-
ones, and the described reaction may be regarded as
a convenient preparative method for the synthesis of
such compounds.
According to the 1H NMR data, compounds Va–Vn
exist exclusively in the enaminodiketone form. This
1
follows from the presence in their H NMR spectra of
a one-proton signal at δ 13–14 ppm, which was as-
signed to the NH proton involved in intramolecular
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RUBINOV et al.
322
1
EXPERIMENTAL
1520 s. H NMR spectrum, δ, ppm: 1.10 s (6H, CH3),
2.44 s (2H, 6-H), 2.58 s (2H, 4-H), 7.38–7.43 m (3H,
m-H, p-H), 7.65–7.68 m (2H, o-H), 7.96 d (1H,
CH=CHPh, J = 15.8 Hz), 8.30 d (1H, CH=CHPh, J =
The IR spectra were recorded on a Bomem
Michelson 100 spectrometer with Fourier transform;
samples were examined as KBr pellets (solid) or films
13
15.8 Hz), 18.53 s (1H, OH, enol). C NMR spectrum,
1
(liquid). The H and 13C NMR spectra were obtained
δC, ppm: 201.78 s, 196.01 s, 187.76 s, 146.04 d,
135.00 s, 130.91 d, 129.04 d, 129.04 d, 128.93 d,
128.93 d, 122.80 d, 111.10 s, 53.17 t, 48.68 t, 30.51 s,
28.25 q, 28.25 q. Found, %: C 75.48; H 6.78. m/z 271
(A) [M + 1]+. C17H18O3. Calculated, %: C 75.53;
H 6.71. M 270.33.
on a Bruker Avance 500 spectrometer at 500 and
125 MHz, respectively, using chloroform-d as solvent
and tetramethylsilane as reference. The mass spectra
(atmospheric pressure chemical ionization) were
recorded using an HPLC–MS/MS system consisting of
an Accell chromatograph and LCQ Fleet mass-selec-
tive detector with positive (A) or negative ion detec-
tion (B). The melting points were determined on
a Boetius melting point apparatus. The progress of
reactions was monitored, and the purity of the isolated
compounds was checked, by TLC on Silufol UV-254
or Alufol UV-254 plates (Merck); spots were detected
by UV irradiation followed by spraying with a solution
of iron(III) chloride. Kieselgel 60 HF254 (Merck) and
Kieselgel 60 (Fluka) were used for chromatographic
separations.
2-[(E)-3-(4-Methoxyphenyl)prop-2-enoyl]-5,5-di-
methylcyclohexane-1,3-dione (IIb). Yield 75% (in the
presence of morpholine), 70% (in the presence of pyr-
rolidine), mp 133–134°C. IR spectrum, ν, cm–1: 1660 s,
1630 s, 1600 v.s, 1570 s, 1520 s, 1250. 1H NMR spec-
trum, δ, ppm: 1.10 s (6H, CH3), 2.43 s (2H, 6-H),
2.56 s (2H, 4-H), 3.85 s (3H, OCH3), 6.92 d (2H, m-H,
J = 8.8 Hz), 7.63 d (2H, o-H, J = 8.8 Hz), 7.95 d (1H,
CH=CHAr, J = 15.8 Hz), 8.21 d.d (1H, CH=CHAr, J =
13
15.8, 0.5 Hz), 18.55 s (1H, OH, enol). C NMR spec-
trum, δC, ppm: 201.83 s, 196.05 s, 187.49 s, 162.13 s,
146.22 d, 131.01 d, 131.01 d, 127.83 s, 120.09 d,
114.44 d, 114.44 d, 110.76 s, 55.44 q, 53.24 t, 48.87 t,
30.47 s, 28.25 q, 28.25 q. Found, %: C 72.11; H 6.82.
m/z 301 (A) [M + 1]+, 299 (B) [M – 1]–. C18H20O4.
Calculated, %: C 71.98; H 6.71. M 300.36.
Condensation of 2-acetylcyclohexane-1,3-diones
Ia and Ib with aromatic aldehydes (general proce-
dure). Triketone Ia or Ib, 0.05 mol, was dissolved in
50 ml of toluene, 0.055 mol of the corresponding
aromatic aldehyde and 0.015 mol of secondary amine
were added, and the mixture was heated for 8–12 h
under reflux in a flask equipped with a Dean–Stark
trap. The mixture was cooled, diluted with 50 ml of
toluene, transferred into a separatory funnel, and ex-
tracted with 50 ml of 20% hydrochloric acid (in one
portion). The aqueous phase was added to 100 ml of
chloroform, and the organic layer was washed with
50 ml of water. The aqueous layers were combined,
and the toluene solution was dried over anhydrous
magnesium sulfate, filtered through a 1-cm layer of
silica gel, and evaporated on a rotary evaporator. The
residue was crystallized from chloroform–methanol to
obtain triketones IIa–IIf in 70–75% yield.
2-[(E)-3-(3,4-Dimethoxyphenyl)prop-2-enoyl]-
5,5-dimethylcyclohexane-1,3-dione (IIc). Yield 73%.
Yellow crystals, mp 194–195°C (decomp.). IR spec-
trum, ν, cm–1: 1655 v.s, 1620 v.s, 1590 s, 1580 v.s,
1515 v.s, 1465 m, 1445 m, 1415 v.s, 1400 v.s, 1250 v.s.
1H NMR spectrum, δ, ppm: 1.00 s (6H, CH3), 2.44 s
(2H, 6-H), 2.56 s (2H, 4-H), 3.94 s and 3.95 s (3H
each, OCH3), 6.87 d (1H, 5-H, J = 8.3 Hz), 7.20 d (1H,
2′-H, J = 1.7 Hz), 7.24 d.d (1H, 6′-H, J = 8.3, 1.7 Hz),
7.94 d (1H, CH=CHAr, J = 15.7 Hz), 8.21 d (1H,
CH=CHAr, J = 15.7 Hz), 18.57 s (1H, OH, enol).
13C NMR spectrum, δC, ppm: 28.25 q, 28.25 q, 30.48 s,
48.87 t, 53.26 t, 55.94 q, 56.02 q, 110.15 d, 110.75 s,
111.01 d, 120.25 d, 124.41 d, 128.13 s, 146.52 d,
149.32 s, 151.97 s, 187.43 s, 196.18 s, 201.89 s.
Found, %: C 68.91; H 6.80. m/z 331 (A) [M + 1]+.
C19H22O5. Calculated, %: C 69.07; H 6.71. M 330.38.
The water–chloroform mixture was separated, the
aqueous phase was extracted with chloroform (2×
25 ml), and the extracts were combined, washed with
50 ml of water, dried over anhydrous MgSO4, and
evaporated on a rotary evaporator. The residue was
crystallized from ethyl acetate–petroleum ether to
isolate 15–20% of enaminodiketones IIIa–IIIg.
5,5-Dimethyl-2-[(E)-3-(2,4,6-trimethylphenyl)-
prop-2-enoyl]cyclohexane-1,3-dione (IId). Yield
70%, light yellow crystals, mp 93–94°C. IR spectrum,
ν, cm–1: 1660 s, 1630 s, 1600 v.s, 1570 s, 1520 s.
1H NMR spectrum, δ, ppm: 1.10 s (6H, CH3), 2.29 s
(3H, 4′-CH3), 2.42 s (2H, 6-H), 2.44 s (6H, 2′-CH3,
5,5-Dimethyl-2-[(E)-3-phenylprop-2-enoyl]cyclo-
hexane-1,3-dione (IIa). Yield 73%, mp 92–93°C. IR
spectrum, ν, cm–1: 1660 s, 1630 s, 1600 v.s, 1570 s,
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SYNTHESIS OF EXO- AND ENDOCYCLIC ENAMINO DERIVATIVES
323
6′-CH3), 2.58 s (2H, 4-H), 6.92 s (2H, Harom), 7.95 d
(1H, CH=CHAr, J = 16.2 Hz), 8.19 d (1H, CH=CHAr,
J = 16.2 Hz), 18.57 (1H, OH, enol, J = 0.6 Hz).
13C NMR spectrum, δC, ppm: 21.17 q, 21.58 q,
21.58 q, 28.28 q, 28.28 q, 30.53 t, 48.63 t, 53.14 t,
111.08 s, 127.01 d, 129.60 d, 129.60 d, 131.13 s,
138.12 s, 138.12 s, 139.30 s, 144.10 d, 188.09 s,
195.82 s, 201.60 s. Found, %: C 76.76; H 7.65.
m/z 313 (A) [M + 1]+, 311 (B) [M – 1]–. C20H24O3.
Calculated, %: C 76.89; H 7.74. M 312.41.
spectrum, δ, ppm: 1.11 s and 1.17 s (6H, CH3), 1.65–
1.77 m (4H, CH2), 1.88 m and 2.00 m (4H,
NCH2CH2), 2.33 s and 2.36 s (4H, 4-H, 6-H), 3.85 m
(4H, NCH2), 7.05 d (1H, CH=CHAr, J = 15.5 Hz),
7.34 d (1H, CH=CHAr, J = 15.5 Hz), 7.35–7.39 m
(3H, m-H, p-H), 7.50 m (2H, o-H). 13C NMR spec-
trum, δC, ppm: 26.08 t, 26.88 t, 27.69 t, 28.25 t,
28.93 q, 28.93 q, 31.35 s, 51.49 t, 51.49 t, 52.36 t,
56.17 t, 108.43 s, 121.04 d, 128.66 d, 128.66 d,
128.86 d, 128.86 d, 130.72 d, 134.86 s, 148.07 d,
178.35 s, 191.87 s, 191.87 s. Found, %: C 78.63;
H 8.30; N 3.94. m/z 352 (A) [M + 1]+, 350 (B) [M – 1]–.
C23H29NO2. Calculated, %: C 78.59; H 8.32; N 3.99.
M 351.49.
2-[(E)-3-(4-Methoxyphenyl)prop-2-enoyl]-5-
(2,4,6-trimethylphenyl)cyclohexane-1,3-dione (IIe).
Yield 75%, mp 184–185°C. IR spectrum, ν, cm–1:
1650 s, 1620 s, 1600 v.s, 1575 s, 1510 v.s, 1470 s,
1
1430 v.s, 1415 v.s, 1250 v.s. H NMR spectrum, δ,
2-[(E)-3-(4-Methoxyphenyl)-1-morpholinoprop-
2-en-1-ylidene]-5,5-dimethylcyclohexane-1,3-dione
(IIIb). Yield 14%, mp 192–193°C. IR spectrum, ν,
cm–1: 1605 s, 1560 v.s, 1555 v.s, 1515 s, 1250 s.
1H NMR spectrum, δ, ppm: 1.14 br.s (6H, CH3),
2.35 br.s (4H, 4-H, 6-H); 3.68 m, 3.90 m, and 3.97 m
[8H, (CH2)2O(CH2)2]; 3.83 s (3H, OCH3), 6.87 d (1H,
CH=CHAr, J = 15.5 Hz), 6.88 d (2H, 3′-H, 5′-H, J =
8.8 Hz), 7.30 d (1H, CH=CHAr, J = 15.5 Hz), 7.45
(2H, 2′-H, 6′-H, J = 8.8 Hz). 13C NMR spectrum, δC,
ppm: 28.85 q, 28.85 q, 31.08 s, 51.11 t, 51.73 t,
54.59 q, 55.44 q, 66.29 t, 66.53 t, 108.30 s, 114.41 d,
114.41 d, 118.17 d, 127.50 s, 130.51 d, 130.51 d,
148.15 d, 161.99 s, 175.73 s, 192.51 s, 192.51 s.
Found, %: C 71.61; H 7.32; N 3.75. m/z 370 (A)
[M + 1]+. C22H27NO4. Calculated, %: C 71.52; H 7.37;
N 3.79. M 369.46.
ppm: 2.26 s (3H, 4′-CH3), 2.38 s (6H, 2′-CH3, 6′-CH3),
2.64 d.d.d (1H, 6-H, J = 16.7, 3.6, 2.3 Hz), 2.72 d.d.d
(1H, 4-H, J = 17.9, 4.0, 2.3 Hz), 3.17 d.d (1H, 6-H, J =
16.7, 14.3 Hz), 3.33 d.d (1H, 4-H, J = 17.9, 13.8 Hz),
3.83 m (1H, 5-H), 3.86 s (3H, OCH3), 6.86 s (2H,
Harom), 6.93 d (2H, 3″-H, 5″-H, J = 8.7 Hz), 7.64 d
(2H, 2″-H, 6″-H, J = 8.7 Hz), 7.98 d (1H, CH=CHAr,
J = 15.7 Hz), 8.22 d (1H, CH=CHAr, J = 15.7 Hz),
18.62 s (1H, OH, enol). 13C NMR spectrum, δC, ppm:
20.61 q, 20.61 q, 21.82 q, 32.49 d, 39.28 t, 43.55 t,
55.45 t, 111.33 s, 114.49 d, 114.49 d, 120.08 d,
127.81 s, 130.77 d, 130.77 d, 131.09 d, 131.09 d,
133.98 s, 136.25 s, 136.49 s, 146.48 d, 162.24 s,
188.31 s, 196.22 s, 202.22 s. Found, %: C 76.79;
H 6.75. m/z 391 (A) [M + 1]+. C25H26O4. Calculated,
%: C 76.90; H 6.71. M 390.48.
2-[(E)-3-(1,3-Benzodioxol-5-yl)prop-2-enoyl]-5-
(2,4,6-trimethylphenyl)cyclohexane-1,3-dione (IIf).
Yield 74%, light yellow crystals, mp 184–185°C. IR
spectrum, ν, cm–1: 1660 s, 1620 s, 1600 s, 1540 s,
2-[(E)-3-(4-Methoxyphenyl)-1-piperidinoprop-
2-en-1-ylidene]-5,5-dimethylcyclohexane-1,3-dione
(IIIc). Yield 20%, mp 200–206°C. IR spectrum, ν,
cm–1: 1630 s, 1600 s, 1560 v.s, 1530 s, 1250. 1H NMR
spectrum, δ, ppm: 1.90 s and 1.20 s (3H each, CH3),
1.74–1.94 m [6H, (CH2)3], 2.36 m (4H, 4-H, 6-H),
3.68 m and 3.88 m (4H, NCH2), 3.84 s (3H, OCH3),
6.88 d (2H, 3′-H, 5′-H, J = 8.8 Hz), 6.89 d (1H,
CH=CHAr, J = 15.5 Hz), 7.28 d (1H, CH=CHAr, J =
15.8 Hz), 7.45 (2H, 2′-H, 6′-H, J = 8.8 Hz). 13C NMR
spectrum, δC, ppm: 23.63 t, 26.39 t, 26.47 t, 28.86 q,
29.00 q, 31.18 s, 51.62 t, 51.62 t, 51.95 t, 55.42 q,
55.54 t, 108.51 s, 114.32 d, 114.32 d, 118.62 d,
127.73 s, 130.35 d, 130.35 d, 147.39 d, 161.74 s,
175.44 s, 192.17 s, 192.17 s. Found, %: C 75.01;
H 8.01; N 3.72. m/z 368 (A) [M + 1]+. C23H29NO3. Cal-
culated, %: C 75.17; H 7.95; N 3.81. M 367.49.
1
1500 s. H NMR spectrum, δ, ppm: 2.26 s (3H,
4′-CH3), 2.38 s (6H, 2′-CH3, 6′-CH3), 2.63 m and
2.72 m (1H each, 6-H), 3.16 d.d (1H, 4-H, J = 16.6,
14.4 Hz), 3.32 d.d (1H, 4-H, J = 17.9, 13.8 Hz), 3.83 m
(1H, 5-H), 6.03 s (2H, OCH2O), 6.83 d (1H, 5″-H, J =
6.8 Hz), 6.86 s (2H, Harom), 7.14 d.d (1H, 6″-H, J = 6.8,
1.0 Hz), 7.22 d (1H, 2″-H, J = 1.0 Hz), 7.91 d (1H,
CH=CHAr, J = 15.7 Hz), 8.16 d (1H, CH=CHAr, J =
15.7 Hz), 18.28 s (1H, OH, enol). Found, %: C 74.06;
H 6.05. m/z 405 (A) [M + 1]+, 403 (B) [M – 1]–.
C25H24O5. Calculated, %: C 74.24; H 5.98. M 404.47.
2-[(E)-1-(Azepan-1-yl)-3-phenylprop-2-en-1-
ylidene]-5,5-dimethylcyclohexane-1,3-dione (IIIa).
Yield 15%, red–brown crystals, mp 187–189°C. IR
spectrum, ν, cm–1: 1610 m, 1565 m, 1520 v.s. 1H NMR
2-[(E)-3-(3,4-Dimethoxyphenyl)-1-piperidino-
prop-2-en-1-ylidene]-5,5-dimethylcyclohexane-1,3-
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RUBINOV et al.
324
dione (IIId). Yield 16%, mp 191–193°C. IR spectrum,
ν, cm–1: 1630 s, 1600 s, 1560 v.s, 1530 s, 1250 v.s.
1H NMR spectrum, δ, ppm: 1.08 s and 1.18 s (3H each,
CH3), 1.73–1.95 m [6H, (CH2)3], 2.35 m (4H, 4-H,
6-H), 3.68 m and 3.88 m (4H, NCH2), 3.91 s (6H,
OCH3), 6.84 d (1H, 5′-H, J = 8.3 Hz), 6.86 d (1H,
CH=CHAr, J = 15.3 Hz), 7.02 d (1H, 2′-H, J =
1.9 Hz), 7.06 d.d (1H, 6′-H, J = 8.3, 1.9 Hz), 7.25 d
(1H, CH=CHAr, J = 15.3 Hz). 13C NMR spectrum, δC,
ppm: 23.60 t, 26.40 t, 26.46 t, 28.91 q, 28.91 q,
31.19 s, 51.60 t, 51.60 t, 52.00 t, 55.57 t, 56.01 q,
56.01 q, 108.67 s, 110.20 d, 110.98 d, 119.04 d,
123.35 d, 128.01 s, 147.43 d, 149.18 s, 151.49 s,
175.29 s, 192.27 s, 192.27 s. Found, %: C 72.68;
H 7.70; N 3.56. m/z 398 (A) [M + 1]+. C24H31NO4.
Calculated, %: C 72.52; H 7.86; N 3.52. M 397.52.
2-[(E)-3-(1,3-Benzodioxol-5-yl)-1-piperidino-
prop-2-en-1-ylidene]-5-(2,4,6-trimethylphenyl)-
cyclohexane-1,3-dione (IIIg). Yield 14%, mp 238–
242°C. IR spectrum, ν, cm–1: 1620 s, 1580 v.s, 1510 s,
1
1500 s. H NMR spectrum, δ, ppm: 1.77–1.94 m [6H,
(CH2)3], 2.25 m (3H, 4′-CH3), 2.42 s (6H, 2′-CH3,
6′-CH3), 2.53 br.d (2H, 4-H, 6-H, J = 15.1 Hz),
3.10 br.s (2H, 4-H, 6-H), 3.78 br.s and 3.92 br.s (4H,
NCH2), 6.02 s (2H, OCH2O), 6.81 d (1H, 5″-H, J =
8.0 Hz), 6.85 s (2H, Harom), 6.93 d (1H, CH=CHAr, J =
15.1 Hz), 7.01 d (1H, 6″-H, J = 8.0 Hz), 7.08 s (1H,
2″-H), 7.38 br.d (1H, CH=CHAr, J = 15.1 Hz). Found,
%: C 76.56; H 7.01; N 3.11. m/z 472 (A) [M + 1]+.
C30H33NO4. Calculated, %: C 76.41; H 7.05; N 2.97.
M 471.60.
Enaminodiketones IIIh–IIIk (general proce-
dures). a. Transamination of enaminodiketones IIIa,
IIIc, and IIIg. The corresponding primary amine,
2.4 mmol, was added to a solution of 2 mmol of
enaminodiketone IIIa, IIIc, or IIIg in 25 ml of
toluene. The mixture was heated for 0.5–1.0 h under
reflux with protection from atmospheric moisture,
cooled to room temperature, filtered through a thin
layer of silica gel, and evaporated on a rotary evap-
orator. The residue was crystallized from ethyl acetate–
petroleum ether.
2-[(E)-1-(Azepan-1-yl)-3-(2,4,6-trimethylphenyl)-
prop-2-en-1-ylidene]-5,5-dimethylcyclohexane-1,3-
dione (IIIe). Yield 15%, mp 150–151°C. IR spectrum,
1
ν, cm–1: 1630 s, 1600 s, 1560 v.s, 1530 s. H NMR
spectrum, δ, ppm: 1.08 s and 1.17 s (3H each, CH3),
1.69 m [4H, (CH2)2], 1.86–1.96 m (4H, NCH2CH2),
2.27 s (3H, 4′-CH3), 2.32 m (4H, 4-H, 6-H), 2.34 s
(6H, 2′-CH3, 6′-CH3), 3.76–3.86 m (4H, NCH2), 6.67 d
(1H, CH=CHAr, J = 15.6 Hz), 6.87 s (2H, Harom),
7.48 d (1H, CH=CHAr, J = 15.5 Hz). 13C NMR spec-
trum, δC, ppm: 21.03 q, 21.03 q, 21.10 q, 26.04 t,
26.90 t, 27.87 t, 28.39 t, 28.85 q, 29.01 q, 31.23 s,
51.72 t, 51.72 t, 52.11 t, 56.06 t, 108.23 s, 126.20 d,
129.25 d, 129.25 d, 131.58 s, 137.23 s, 137.23 s,
138.91 s, 146.65 d, 178.00 s, 191.98 s, 191.98 s.
Found, %: C 79.39; H 8.87; N 3.67. m/z 394 (A)
[M + 1]+. C26H35NO2. Calculated, %: C 79.35; H 8.96;
N 3.56. M 393.57.
b. The corresponding primary aliphatic amine,
2.4 mmol, was added to a solution of 2 mmol of tri-
ketone IIa, IIb, or IIc in 25 ml of toluene. The mixture
was heated for 3–4 h in a flask equipped with a Dean–
Stark trap, cooled to room temperature, filtered
through a thin layer of silica gel, and evaporated on
a rotary evaporator. The residue was crystallized from
ethyl acetate–petroleum ether. Enaminodiketones
IIIh–IIIk thus obtained were identical in physical
parameters to samples prepared as described in a.
2-[(E)-3-(4-Methoxyphenyl)-1-(pyrrolidin-1-yl)-
prop-2-en-1-ylidene]-5-(2,4,6-trimethylphenyl)cy-
clohexane-1,3-dione (IIIf). Yield 18%, dark yellow
crystals, mp 207–209°C. IR spectrum, ν, cm–1: 1625 s,
1600 v.s, 1560 v.s, 1550 v.s, 1535 v.s, 1510 v.s,
2-[(E)-1-(4-Methoxybenzylamino)-3-phenylprop-
2-en-1-ylidene]-5,5-dimethylcyclohexane-1,3-dione
(IIIh). Yield 74% (a), 56% (b); light yellow crystals,
mp 152–153°C. IR spectrum, ν, cm–1: 1650 s, 1635 s,
1565 v.s, 1555 v.s, 1510 s, 1250. 1H NMR spectrum, δ,
ppm: 1.06 s (6H, CH3), 2.40 s (4H, 4-H, 6-H), 3.81 s
(3H, OCH3), 4.70 d (2H, CH2N, J = 6.0 Hz), 6.61 d
(1H, CH=CHAr, J = 16.8 Hz), 6.91 d (2H, 3′-H, 5′-H,
J = 8.7 Hz), 7.20 d (2H, 2′-H, 6′-H, J = 8.7 Hz), 7.27 d
(1H, CH=CHAr, J = 16.8 Hz), 7.29–7.39 m (3H, m-H,
p-H), 7.50 d (2H, o-H), 13.56 br.s (1H, NH). 13C NMR
spectrum, δC, ppm: 28.36 q, 28.36 q, 30.39 s, 48.65 t,
48.65 t, 52.68 t, 55.33 q, 108.07 s, 114.47 d, 114.47 d,
122.98 d, 127.27 d, 127.27 d, 128.51 d, 128.51 d,
1
1400 v.s, 1250 v.s. H NMR spectrum, δ, ppm: 2.03 m
and 2.20 m (4H, CH2CH2), 2.26 s (3H, 4′-CH3), 2.44 s
(6H, 2′-CH3, 6′-CH3), 2.45–2.53 m (2H, 4-H, 6-H),
3.02–3.26 m (2H, 4-H, 6-H), 3.85 s (3H, OCH3), 3.91 t
and 3.96 t (4H, NCH2, J = 7.0 Hz), 6.86 s (2H, Harom),
6.89 d (1H, CH=CHAr, J = 17.0 Hz), 6.90 d (2H,
3″-H, 5″-H, J = 8.6 Hz), 7.52 d (2H, 2″-H, 6″-H,
J = 8.6 Hz), 7.54 br.s (1H, CH=CHAr). Found, %:
C 78.68; H 7.77; N 3.15. m/z 458 (A) [M + 1]+.
C30H35NO3. Calculated, %: C 78.74; H 7.71; N 3.06.
M 457.62.
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SYNTHESIS OF EXO- AND ENDOCYCLIC ENAMINO DERIVATIVES
325
128.80 d, 128.80 d, 128.88 s, 129.03 d, 134.83 d,
135.49 s, 159.34 s, 169.80 s, 197.94 s, 197.94 s.
Found, %: C 77.21; H 7.13; N 3.67. m/z 390 (A)
[M + 1]+. C25H27NO3. Calculated, %: C 77.09; H 6.99;
N 3.60. M 389.50.
15.6 Hz), 7.89 d (1H, CH=CHAr, J = 15.6 Hz),
13.02 br.s (1H, NH). 13C NMR spectrum, δC, ppm:
20.62 q, 20.62 q, 21.94 q, 31.27 q, 33.38 d, 42.29 t,
47.08 t, 55.34 q, 101.32 t, 107.03 d, 108.35 d,
109.20 s, 114.53 d, 114.53 d, 124.21 d, 126.85 d,
127.69 s, 128.42 d, 128.42 d, 129.03 s, 130.64 s,
130.97 s, 134.34 s, 136.43 s, 136.60 d, 136.60 d,
139.63 d, 148.12 s, 148.85 s, 159.41 s, 173.16 s,
191.17 s, 195.49 s. Found, %: C 75.76; H 6.47; N 2.68.
m/z 524 (A) [M + 1]+. C33H33NO5. Calculated, %:
C 75.70; H 6.35; N 2.67. M 523.63.
2-[(E)-1-(Isopropylamino)-3-(4-methoxyphenyl)-
prop-2-en-1-ylidene]-5,5-dimethylcyclohexane-1,3-
dione (IIIi). Yield 70% (a), 50% (b); mp 111–112°C.
IR spectrum, ν, cm–1: 1640 v.s, 1590 v.s, 1560 s,
1
1550 v.s, 1515 v.s, 1450 s, 1250 s. H NMR spectrum,
δ, ppm: 1.50 s (6H, CH3), 1.32 d [6H, (CH3)2CH],
2.38 s (4H, 4-H, 6-H), 3.83 s (3H, OCH3), 4.21–4.29 m
(1H, NCH), 6.57 d (1H, CH=CHAr, J = 16.7 Hz),
6.90 d (2H, 3′-H, 5′-H, J = 8.7 Hz), 7.07 d (1H,
CH=CHAr, J = 16.7 Hz), 7.48 (2H, 2′-H, 6′-H, J =
8.7 Hz), 13.20 br.d (1H, NCH, J = 6.8 Hz). 13C NMR
spectrum, δC, ppm: 23.85 q, 23.85 q, 28.37 q, 28.37 q,
30.39 s, 46.71 d, 52.71 t, 52.71 t, 55.38 q, 107.64 s,
114.24 d, 114.24 d, 121.09 d, 128.40 s, 128.61 d,
128.61 d, 133.15 d, 160.32 s, 168.84 s, 197.70 s,
197.70 s. Found, %: C 73.86; H 7.92; N 4.15. m/z 342
(A) [M + 1]+. C21H27NO3. Calculated, %: C 73.87;
H 7.97; N 4.10. M 341.45.
Enol methyl ethers IVa–IVc (general procedure).
Triketone IIa, IIb, or IIf, 50 mmol, was dissolved in
100 ml of toluene, 34.5 g (0.25 mol) of finely
powdered anhydrous potassium carbonate and 5.7 ml
(60 mmol) of dimethyl sulfate were added under
stirring, and the mixture was heated for 8–12 h under
reflux with vigorous stirring with protection from
atmospheric moisture. The precipitate of potassium
carbonate was filtered off and washed with 100 ml of
anhydrous chloroform. The toluene and chloroform
solutions were combined, filtered through a 1-cm layer
of silica gel, and evaporated on a rotary evaporator.
The residue was crystallized from ethyl acetate–di-
ethyl ether.
2-[(E)-1-Benzylamino-3-(4-methoxyphenyl)prop-
2-en-1-ylidene]-5,5-dimethylcyclohexane-1,3-dione
(IIIj). Yield 75% (a), 60% (b); light yellow crystals,
mp 100–101°C. IR spectrum, ν, cm–1: 1640 s, 1630 s,
1565 v.s, 1555 v.s, 1510 s, 1240. 1H NMR spectrum, δ,
ppm: 1.06 s (6H, CH3), 2.41 s (4H, 4-H, 6-H), 3.82 s
(3H, OCH3), 4.77 d (2H, CH2N, J = 6.0 Hz), 6.58 d
(1H, CH=CHAr, J = 16.8 Hz), 6.88 d (2H, 3′-H, 5′-H,
J = 8.7 Hz), 7.16 d (1H, CH=CHAr, J = 16.8 Hz),
7.25–7.43 m (7H, C6H5, 2′-H, 6′-H), 13.64 br.s (1H,
NH). Found, %: C 77.21; H 7.13; N 3.67. m/z 390 (A)
[M + 1]+. C25H27NO3. Calculated, %: C 77.09; H 6.99;
N 3.60. M 389.50.
3-Methoxy-5,5-dimethyl-2-[(E)-3-phenylprop-
2-enoyl]cyclohex-2-en-1-one (IVa). Yield 75%,
mp 102–103°C. IR spectrum, ν, cm–1: 1660 s, 1620 s,
1
1600 s, 1540 s, 1500 s, 1250. H NMR spectrum, δ,
ppm: 1.19 s (6H, CH3), 2.23 s (2H, 6-H), 2.51 s (2H,
4-H), 3.81 s (3H, OCH3), 6.87 d (1H, CH=CHAr, J =
16.1 Hz), 7.35–7.40 m (3H, m-H, p-H), 7.44 d (1H,
CH=CHAr, J = 16.1 Hz), 7.51–7.55 m (2H, o-H).
Found, %: C 76.21; H 7.01. m/z 285 (A) [M + 1]+.
C18H20O3. Calculated, %: C 76.03; H 7.09. M 284.36.
3-Methoxy-2-[(E)-3-(4-methoxyphenyl)prop-2-
enoyl]-5,5-dimethylcyclohex-2-en-1-one (IVb). Yield
80%, mp 84–86°C. IR spectrum, ν, cm–1: 1650 s,
2-[(E)-3-(1,3-Benzodioxol-5-yl)-1-(4-methoxy-
benzylamino)prop-2-en-1-ylidene]-5-(2,4,6-trimeth-
ylphenyl)cyclohexane-1,3-dione (IIIk). Yield 72%
(a), 50% (b), mp 163–165°C. IR spectrum, ν, cm–1:
3100 s, 1640 s, 1610 s, 1570 v.s, 1560 v.s, 1240 v.s.
1H NMR spectrum, δ, ppm: 2.26 s (3H, 4′-CH3),
2.34 br.s (6H, 2′-CH3, 6′-CH3), 2.57 br.d (1H, 6-H, J =
16.7 Hz), 2.84 br.d (1H, 4-H, J = 17.3 Hz), 3.01–
3.13 m (2H, 4-H, 6-H), 3.75 m (1H, 5-H), 3.81 s (3H,
OCH3), 4.48 m (2H, NHCH2), 5.98 s (2H, OCH2O),
6.78 d (1H, 5″-H, J = 8.0 Hz), 6.86 s (2H, Harom),
6.89 d (2H, 3′′′-H, 5′′′-H, J = 8.6 Hz), 7.06 d (1H,
6″-H, J = 8.0 Hz), 7.17 br.s (1H, 2″-H), 7.19 d (2H,
2′′′-H, 6′′′-H, J = 8.6 Hz), 7.53 d (1H, CH=CHAr, J =
1
1620 s, 1600 v.s, 1560 m, 1510 m, 1250. H NMR
spectrum, δ, ppm: 1.19 s (6H, CH3), 2.33 s (2H, 6-H),
2.50 s (2H, 4-H), 3.81 s (3H, 3-OCH3), 3.84 s (3H,
4′-OCH3), 6.76 d (1H, CH=CHAr, J = 16.0 Hz), 6.89 d
(2H, 3′-H, 5′-H, J = 8.7 Hz), 7.39 d (1H, CH=CHAr,
J = 16.0 Hz), 7.48 d (2H, 2′-H, 6′-H, J = 8.7 Hz).
Found, %: C 72.72; H 7.00. m/z 315 (A) [M + 1]+.
C19H22O4. Calculated, %: C 72.59; H 7.05. M 314.38.
2-[(E)-3-(1,3-Benzodioxol-5-yl)prop-2-enoyl]-3-
methoxy-5-(2,4,6-trimethylphenyl)cyclohex-2-en-1-
one (IVc). Yield 77%, mp 171–172°C. IR spectrum, ν,
cm–1: 1660 s, 1620 s, 1600 s, 1540 s, 1500 s, 1250.
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1H NMR spectrum, δ, ppm: 2.27 s (3H, 4′-CH3), 2.42 s
(6H, 2′-CH3, 6′-CH3), 2.53 d.d (1H, 6-H, J = 16.5,
4.3 Hz), 2.73 d.d (1H, 4-H, J = 18.1, 5.1 Hz), 3.13 m
(1H, 4-H, 6-H), 3.82 s (3H, OCH3), 3.90 m (1H, 5-H),
6.01 s (2H, OCH2O), 6.76 d (1H, CH=CHAr, J =
15.9 Hz), 6.81 d (1H, 5′-H, J = 8.0 Hz), 6.90 s (2H,
Harom), 7.04 d.d (1H, 6′-H, J = 8.0, 1.5 Hz), 7.08 d
(1H, 2′-H, J = 1.5 Hz), 7.42 d (1H, CH=CHAr, J =
15.9 Hz). Found, %: C 74.76; H 6.35. m/z 419 (A)
[M + 1]+. C26H26O5. Calculated, %: C 74.62; H 6.26.
M 418.49.
2-[(E)-3-(4-Methoxyphenyl)prop-2-enoyl]-5,5-
dimethyl-3-methylaminocyclohex-2-en-1-one (Vc).
Yield 93%, mp 155–156°C. IR spectrum, ν, cm–1:
1630 m, 1580 v.s, 1550 s, 1515 s, 1470 m, 1420 m,
1
1250 v.s. H NMR spectrum, δ, ppm: 1.11 s (6H,
5-CH3), 2.34 s (2H, 6-H), 2.47 s (2H, 4-H), 3.07 d (3H,
NHCH3, J = 5.2 Hz), 3.83 s (3H, OCH3), 6.87 d (2H,
3′-H, 5′-H, J = 8.7 Hz), 7.56 d (2H, 2′-H, 6′-H, J =
8.7 Hz), 7.57 d (1H, CH=CHAr, J = 15.5 Hz), 8.00 d
(1H, CH=CHAr, J = 15.5 Hz), 12.80 br.s (1H, NH).
13C NMR spectrum, δC, ppm: 28.46 q, 28.46 q,
30.20 q, 30.61 s, 40.30 t, 52.10 t, 55.32 q, 108.41 s,
108.41 s, 114.05 d, 114.05 d, 126.66 d, 129.04 s,
129.84 d, 129.84 d, 129.84 d, 139.40 d, 160.64 s,
173.17 s, 190.73 s, 194.80 s. Found, %: C 72.72;
H 7.51; N 4.39. m/z 314 [M + 1]+. C19H23NO3. Cal-
culated, %: C 72.82; H 7.40; N 4.47. M 313.40.
Enaminodiketones Va–Vp (general procedure).
The corresponding amine, 3 mmol, was added to a so-
lution of 3 mmol of methyl ether IVa–IVc in 25 ml of
anhydrous chloroform, and the mixture was stirred for
2–5 h at room temperature under nitrogen or argon.
When the reaction was complete (TLC), the mixture
was filtered through a thin layer of silica gel and
evaporated on a rotary evaporator. The residue was
crystallized from ethyl acetate–petroleum ether.
3-Isopropylamino-2-[(E)-3-(4-methoxyphenyl)-
prop-2-enoyl]-5,5-dimethylcyclohex-2-en-1-one
(Vd). Yield 95%, mp 135–136°C. IR spectrum, ν,
cm–1: 1660 s, 1620 s, 1600 s, 1540 s, 1500 s. 1H NMR
spectrum, δ, ppm: 1.11 s (6H, 5-CH3), 1.34 d [6H,
(CH3)2CH, J = 6.4 Hz], 2.34 s (2H, 6-H), 2.52 s (2H,
4-H), 3.82 s (3H, OCH3), 3.89 m (1H, NCH), 6.87 d
(2H, 3′-H, 5′-H, J = 8.8 Hz), 7.55 d (2H, 2′-H, 6′-H,
J = 8.8 Hz), 7.56 d (1H, CH=CHAr, J = 15.6 Hz),
7.96 d (1H, CH=CHAr, J = 15.6 Hz), 13.00 d (1H,
NH, J = 6.0 Hz). Found, %: C 73.67; H 7.81; N 4.12.
m/z 342 [M + 1]+. C21H27NO3. Calculated, %: C 73.87;
H 7.97; N 4.10. M 341.45.
3-(3,4-Dimethylphenylamino)-5,5-dimethyl-2-
[(E)-3-phenylprop-2-enoyl]cyclohex-2-en-1-one
(Va). Yield 83%, mp 124–125°C. IR spectrum, ν, cm–1:
1640 s, 1560 v.s, 1545 v.s. 1H NMR spectrum, δ, ppm:
1.03 s (6H, 5-CH3), 2.29 s (6H, 3′-CH3, 4′-CH3), 2.38 s
(2H, 6-H), 2.49 s (2H, 4-H), 6.90 d.d (1H, 6′-H, J =
7.9, 1.5 Hz), 6.90 d (1H, 2′-H, J = 1.5 Hz), 7.18 d (1H,
5′-H, J = 7.9 Hz), 7.30–7.39 m (3H, m-H, p-H), 7.63 d
(2H, o-H), 7.64 d (1H, CH=CHAr, J = 15.6 Hz),
8.12 d (1H, CH=CHAr, J = 15.6 Hz), 14.32 br.s (1H,
NH). 13C NMR spectrum, δC, ppm: 19.40 q, 19.86 q,
28.04 q, 28.04 q, 31.30 s, 41.70 t, 52.49 t, 108.86 s,
123.11 d, 126.83 d, 128.32 d, 128.32 d, 128.61 d,
128.61 d, 128.68 d, 129.31 d, 130.50 d, 134.62 s,
136.15 s, 136.25 s, 138.13 s, 139.95 d, 171.38 s,
191.01 s, 195.44 s. Found, %: C 80.52; H 7.38; N 3.59.
m/z 374 (A) [M + 1]+. C25H27NO2. Calculated, %:
C 80.40; H 7.29; N 3.75. M 373.50.
3-Benzylamino-2-[(E)-3-(4-methoxyphenyl)prop-
2-enoyl]-5,5-dimethylcyclohex-2-en-1-one (Ve).
Yield 94%, mp 148–149°C. IR spectrum, ν, cm–1:
1660 s, 1620 s, 1600 s, 1540 s, 1500 s. 1H NMR spec-
trum, δ, ppm: 1.05 s (6H, 5-CH3), 2.34 s (2H, 6-H),
2.49 s (2H, 4-H), 3.82 s (3H, OCH3), 4.59 d (2H,
CH2NH, J = 5.9 Hz), 6.87 d (2H, 3′-H, 5′-H, J =
8.7 Hz), 7.27–7.41 m (5H, C6H5), 7.56 d (2H, 2′-H,
6′-H, J = 8.7 Hz), 7.58 d (1H, CH=CHAr, J =
16.0 Hz), 7.99 s (1H, CH=CHAr, J = 16.0 Hz),
13.24 br.s (1H, NH). 13C NMR spectrum, δC, ppm:
28.32 q, 28.32 q, 30.80 s, 40.45 t, 47.44 t, 52.12 t,
55.32 q, 108.67 s, 114.06 d, 114.06 d, 126.59 d,
126.96 d, 126.96 d, 128.06 d, 128.98 s, 129.15 d,
129.15 d, 129.86 d, 129.86 d, 136.13 s, 139.61 d,
160.68 s, 172.52 s, 190.95 s, 194.99 s. Found, %:
C 77.01; H 7.00; N 3.45. m/z 390 (A) [M + 1]+.
C25H27NO3. Calculated, %: C 77.09; H 6.99; N 3.60.
M 389.50.
3-(4-Methoxyphenylamino)-5,5-dimethyl-2-
[(E)-3-phenylprop-2-enoyl]cyclohex-2-en-1-one
(Vb). Yield 87%, mp 131–132°C. IR spectrum, ν,
1
cm–1: 1640 s, 1560 v.s, 1545 v.s, 1250. H NMR spec-
trum, δ, ppm: 1.10 s (6H, 5-CH3), 2.36 s (2H, 6-H),
2.50 s (2H, 4-H), 3.80 s (3H, OCH3), 6.92 d (2H, 3′-H,
5′-H, J = 8.7 Hz), 7.04 d (2H, 2′-H, 6′-H, J = 8.7 Hz),
7.31 d (1H, CH=CHAr, J = 15.8 Hz), 7.44 d (1H,
CH=CHAr, J = 15.8 Hz), 7.30–7.39 m (3H, m-H,
p-H), 7.63 d (2H, o-H), 14.32 br.s (1H, NH). Found,
%: C 76.58; H 6.88; N 3.69. m/z 376 (A) [M + 1]+.
C24H25NO3. Calculated, %: C 76.77; H 6.71; N 3.73.
M 375.47.
2-[(E)-3-(4-Methoxyphenyl)prop-2-enoyl]-5,5-
dimethyl-3-(4-methylbenzylamino)cyclohex-2-en-1-
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SYNTHESIS OF EXO- AND ENDOCYCLIC ENAMINO DERIVATIVES
327
one (Vf). Yield 95%, mp 153–154°C. IR spectrum, ν,
cm–1: 1660 s, 1620 s, 1600 s, 1540 s, 1500 s. 1H NMR
spectrum, δ, ppm: 1.05 s (6H, 5-CH3), 2.33 s (2H,
6-H), 2.35 s (3H, 4″-CH3), 2.49 s (2H, 4-H), 3.82 s
(3H, OCH3), 4.54 d (2H, CH2N, J = 5.8 Hz), 6.87 d
(2H, 3′-H, 5′-H, J = 8.8 Hz), 7.18 m (4H, Harom), 7.56 d
(2H, 2′-H, 6′-H, J = 8.8 Hz), 7.57 d (1H, CH=CHAr,
J = 15.8 Hz), 7.99 d (1H, CH=CHAr, J = 15.8 Hz),
13.18 br.s (1H, NH). Found, %: C 77.27; H 7.38;
N 3.35. m/z 404 (A) [M + 1]+. C26H29NO3. Calculated,
%: C 77.39; H 7.24; N 3.47. M 403.52.
28.05 q, 31.29 s, 41.73 t, 52.55 t, 55.33 q, 108.89 s,
114.10 d, 114.10 d, 125.72 d, 125.72 d, 126.32 d,
128.02 s, 129.97 d, 129.97 d, 130.12 d, 130.12 d,
134.53 s, 137.47 s, 140.12 d, 160.80 s, 171.22 s,
191.13 s, 195.40 s. Found, %: C 77.12; H 7.18; N 3.67.
m/z 390 (A) [M + 1]+. C25H27NO3. Calculated, %:
C 77.09; H 6.99; N 3.60. M 389.50.
3-(4-Methoxyphenylamino)-2-[(E)-3-(4-methoxy-
phenyl)prop-2-enoyl]-5,5-dimethylcyclohex-2-en-1-
one (Vj). Yield 88%, mp 140–142°C. IR spectrum, ν,
cm–1: 1660 s, 1620 s, 1600 s, 1540 s, 1500 s, 1250 s.
1H NMR spectrum, δ, ppm: 1.10 s (6H, 5-CH3), 2.42 s
(2H, 6-H), 2.48 s (2H, 4-H), 3.83 s and 3.86 s (3H
each, OCH3), 6.84 d (2H, 2′-H, 6′-H, J = 8.7 Hz),
6.88 d (2H, 3″-H, 5″-H, J = 8.8 Hz), 7.10 d (2H, 3′-H,
5′-H, J = 8.7 Hz), 7.59 d (2H, 2″-H, 6″-H, J = 8.8 Hz),
7.64 d (1H, CH=CHAr, J = 15.7 Hz), 8.00 d (1H,
CH=CHAr, J = 15.7 Hz), 14.38 br.s (1H, NH). Found,
%: C 74.21; H 6.89; N 3.63. m/z 406 (A) [M + 1]+.
C25H27NO4. Calculated, %: C 74.05; H 6.71; N 3.45.
M 405.50.
3-(4-Methoxybenzylamino)-2-[(E)-3-(4-methoxy-
phenyl)prop-2-enoyl]-5,5-dimethylcyclohex-2-en-1-
one (Vg). Yield 92%, mp 149–150°C. IR spectrum, ν,
cm–1: 1660 s, 1620 s, 1600 s, 1540 s, 1500 s. 1H NMR
spectrum, δ, ppm: 1.06 s (6H, 5-CH3), 2.34 s (2H,
6-H), 2.50 s (2H, 4-H), 3.81 s and 3.82 s (3H each,
OCH3), 4.52 d (2H, CH2N, J = 5.7 Hz), 6.87 d (2H,
3′-H, 5′-H, J = 8.8 Hz), 6.91 d (2H, 3″-H, 5″-H, J =
8.7 Hz), 7.21 d (2H, 2″-H, 6″-H, J = 8.7 Hz), 7.56 d
(2H, 2′-H, 6′-H, J = 8.8 Hz), 7.56 d (1H, CH=CHAr,
J = 15.5 Hz), 7.99 d (1H, CH=CHAr, J = 15.5 Hz),
13.14 br.s (1H, NH). Found, %: C 74.57; H 6.88;
N 3.59. m/z 420 (A) [M + 1]+. C26H29NO4. Calculated,
%: C 74.44; H 6.97; N 3.34. M 419.52.
3-Allylamino-2-[(E)-3-(1,3-benzodioxol-5-yl)-
prop-2-enoyl]-5-(2,4,6-trimethylphenyl)cyclohex-2-
en-1-one (Vk). Yield 91%, oily substance. IR spec-
trum, ν, cm–1: 3100 w, 1640 s, 1610 , 1580 v.s, 1500 s.
1H NMR spectrum, δ, ppm: 2.27 s (3H, 4′-CH3), 2.38 s
(6H, 2′-CH3, 6′-CH3), 2.59 d.d.d (1H, 6-H, J = 16.7,
4.0, 1.9 Hz), 2.78 d.d.d (1H, 4-H, J = 17.2, 4.1,
1.9 Hz), 3.06 d.d (1H, 4-H, J = 17.2, 13.3 Hz), 3.10 d.d
(1H, 6-H, J = 16.7, 14.4 Hz), 3.75 m (1H, 5-H), 3.98 m
(2H, NHCH2), 5.24–5.32 m (2H, CH=CH2), 5.84–
5.93 m (1H, CH=CH2), 5.98 s (2H, OCH2O), 6.79 d
(1H, 5″-H, J = 8.0 Hz), 6.88 s (3′-H, 5′-H), 7.08 d.d
(1H, 6″-H, J = 8.0, 1.5 Hz), 7.18 d (1H, 2″-H, J =
1.5 Hz), 7.55 d (1H, CH=CHAr, J = 15.6 Hz), 7.90 d
(1H, CH=CHAr, J = 15.6 Hz), 12.84 br.s (1H, NH).
Found, %: C 76.56; H 7.01; N 2.88. m/z 472 (A)
[M + 1]+. C30H33NO4. Calculated, %: C 76.41; H 7.05;
N 2.97. M 471.60.
3-(3,4-Dimethylphenylamino)-2-[(E)-3-(4-me-
thoxyphenyl)prop-2-enoyl]-5,5-dimethylcyclohex-
2-en-1-one (Vh). Yield 85%, mp 144–147°C. IR spec-
trum, ν, cm–1: 1640 m, 1610 m, 1560 v.s, 1510 m,
1
1250 s. H NMR spectrum, δ, ppm: 1.03 s (6H,
5-CH3), 2.29 s (6H, 3′-CH3, 4′-CH3), 2.39 s (2H, 6-H),
2.48 s (2H, 4-H), 3.84 s (3H, OCH3), 6.88 d (2H, 3″-H,
5″-H, J = 8.7 Hz), 6.89 d.d (1H, 6′-H, J = 7.9, 2.1 Hz),
6.95 d (1H, 2′-H, J = 2.1 Hz), 7.18 d (1H, 5′-H, J =
7.9 Hz), 7.59 d (2H, 2″-H, 6″-H, J = 8.7 Hz), 7.64 d
(1H, CH=CHAr, J = 15.7 Hz), 8.01 d (1H, CH=CHAr,
J = 15.7 Hz), 14.36 br.s (1H, NH). Found, %: C 77.28;
H 7.33; N 3.67. m/z 404 (A) [M + 1]+. C26H29NO3.
Calculated, %: C 77.39; H 7.24; N 3.47. M 403.52.
2-[(E)-3-(4-Methoxyphenyl)prop-2-enoyl]-5,5-
dimethyl-3-(4-methylphenylamino)cyclohex-2-en-1-
one (Vi). Yield 86%, mp 130–131°C. IR spectrum, ν,
cm–1: 1660 s, 1620 s, 1600 s, 1540 s, 1500 s. 1H NMR
spectrum, δ, ppm: 1.03 s (6H, 5-CH3), 2.38 s (2H,
6-H), 2.40 s (3H, 4″-CH3), 2.47 s (2H, 4-H), 3.83 s
(3H, 4′-OCH3), 6.89 d (2H, 3′-H, 5′-H, J = 8.0 Hz),
7.06 d (2H, 2″-H, 6″-H, J = 7.6 Hz), 7.23 d (2H, 3″-H,
5″-H, J = 7.6 Hz), 7.59 d (2H, 2′-H, 6′-H, J = 8.0 Hz),
7.64 d (1H, CH=CHAr, J = 15.7 Hz), 8.03 d (1H,
CH=CHAr, J = 15.7 Hz), 14.38 br.s (1H, NH).
13C NMR spectrum, δC, ppm: 21.08 q, 28.05 q,
2-[(E)-3-(1,3-Benzodioxol-5-yl)prop-2-enoyl]-3-
(4-methoxybenzylamino)-5-(2,4,6-trimethylphenyl)-
cyclohex-2-en-1-one (Vl). Yield 94%, mp 163–165°C.
IR spectrum, ν, cm–1: 3100 s, 1640 s, 1610 s, 1570 v.s,
1
1560 v.s, 1240 v.s. H NMR spectrum, δ, ppm: 2.26 s
(3H, 4′-CH3), 2.34 br.s (6H, 2′-CH3, 6′-CH3), 2.57 br.d
(1H, 6-H, J = 16.7 Hz), 2.84 br.d (1H, 4-H, J =
17.3 Hz), 3.0–3.13 m (2H, 4-H, 6-H), 3.75 m (1H,
5-H), 3.81 s (3H, OCH3), 4.48 m (2H, NHCH2), 5.98 s
(2H, OCH2O), 6.78 d (1H, 5″-H, J = 8.0 Hz), 6.86 s
(2H, 3′-H, 5′-H), 6.89 d (2H, 3′′′-H, 5′′′-H, J = 8.6 Hz),
7.06 d (1H, 6″-H, J = 8.0 Hz), 7.17 br.s (1H, 2″-H),
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7.19 d (2H, 2′′′-H, 6′′′-H, J = 8.6 Hz), 7.53 d (1H,
CH=CHAr, J = 15.6 Hz), 7.89 d (1H, CH=CHAr, J =
15.6 Hz), 13.02 br.s (1H, NH). 13C NMR spectrum, δC,
ppm: 20.61 q, 20.61 q, 21.94 q, 31.27 t, 33.38 d,
42.29 t, 41.08 t, 55.37 q, 101.32 t, 107.03 d, 108.35 d,
109.20 s, 114.53 d, 114.53 d, 124.21 d, 126.85 d,
127.69 s, 128.42 d, 128.42 d, 129.03 s, 130.64 s,
130.97 s, 134.34 s, 136.43 s, 136.60 d, 136.60 d,
139.63 d, 148.12 s, 148.85 s, 159.415 s, 173.16 s,
191.17 s, 195.49 s. Found, %: C 75.76; H 6.47; N 2.68.
m/z 524 (A) [M + 1]+. C33H33NO5. Calculated, %:
C 75.70; H 6.35; N 2.67. M 523.63.
107.08 d, 108.38 d, 109.41 s, 124.38 d, 125.56 d,
125.56 d, 126.54 d, 130.20 d, 130.20 d, 130.59 s,
134.31 s, 134.39 s, 136.35 d, 136.35 d, 136.49 s,
137.61 s, 140.24 d, 148.18 s, 149.00 s, 172.43 s,
191.34 s, 195.98 s. Found, %: C 75.56; H 6.27; N 2.82.
m/z 494 (A) [M + 1]+. C32H31NO4. Calculated, %:
C 77.87; H 6.33; N 2.84. M 493.61.
2-[(E)-3-(4-Methoxyphenyl)prop-2-enoyl]-5,5-di-
methyl-3-piperidinocyclohex-2-en-1-one (Vo). Yield
93%, oily substance. IR spectrum, ν, cm–1: 1650 s,
1
1610 s, 1580 s, 1520 v.s. H NMR spectrum, δ, ppm:
1.17 s (6H, 5-CH3), 1.61–1.74 m [6H, (CH2)3], 2.29 s
(2H, 6-H), 2.45 s (2H, 4-H), 3.28 m (4H, NCH2),
3.82 s (3H, OCH3), 6.87 d (2H, 3′-H, 5′-H, J = 8.7 Hz),
7.31 d (1H, CH=CHAr, J = 15.8 Hz) , 7.48 d (1H,
CH=CHAr, J = 15.8 Hz), 7.54 d (2H, 2′-H, 6′-H, J =
8.7 Hz). Found, %: C 75.23; H 7.91; N 3.90. m/z 368
(A) [M + 1]+. C23H29NO3. Calculated, %: C 75.17;
H 7.95; N 3.81. M 367.49.
2-[(E)-3-(1,3-Benzodioxol-5-yl)prop-2-enoyl]-3-
(4-methoxyphenylamino)-5-(2,4,6-trimethylphenyl)-
cyclohex-2-en-1-one (Vm). Yield 86%, mp 187–
189°C. IR spectrum, ν, cm–1: 1630 m, 1550 v.s, 1510 s,
1
1490 s, 1240 v.s. H NMR spectrum, δ, ppm: 2.22 s
(3H, 4′-CH3), 2.35 s (6H, 2′-CH3, 6′-CH3), 2.64 m (2H,
4-H, 6-H), 3.12 m (2H, 4-H, 6-H), 3.71 m (1H, 5-H),
3.79 s (3H, OCH3), 5.99 s (2H, OCH2O), 6.80 d (1H,
5″-H, J = 8.0 Hz), 6.82 s (3′-H, 5′-H), 6.88 d (2H,
2′′′-H, 6′′′-H, J = 8.8 Hz), 7.07 d (1H, 3′′′-H, 5′′′-H, J =
8.8 Hz), 7.10 br.d (1H, 6″-H, J = 8.0 Hz), 7.20 br.s
(1H, 2″-H), 7.62 d (1H, CH=CHAr, J = 15.6 Hz),
7.95 d (1H, CH=CHAr, J = 15.6 Hz), 14.15 br.s (1H,
NH). 13C NMR spectrum, δC, ppm: 20.56 q, 20.56 q,
21.99 q, 32.55 t, 34.05 d, 42.70 t, 55.51 q, 101.37 t,
107.05 d, 108.38 d, 109.37 s, 114.80 d, 114.80 d,
124.39 d, 126.52 d, 126.96 d, 126.96 d, 129.61 s,
130.56 s, 130.56 s, 134.38 s, 136.35 d, 136.51 s,
140.20 d, 140.20 d, 148.16 s, 148.29 s, 148.99 s,
158.80 s, 172.70 s, 191.31 s, 195.98 s. Found, %:
C 75.56; H 6.27; N 2.82. m/z 510 (A) [M + 1]+.
C32H31NO5. Calculated, %: C 75.42; H 6.13; N 2.75.
M 509.61.
2-[(E)-3-(1,3-Benzodioxol-5-yl)prop-2-enoyl]-3-
piperidino-5-(2,4,6-trimethylphenyl)cyclohex-2-en-
1-one (Vp). Yield 94%, oily substance. IR spectrum, ν,
cm–1: 1640 s, 1610 s, 1600 s, 1560 s, 1490 v.s.
1H NMR spectrum, δ, ppm: 1.62–1.75 m [6H, (CH2)3],
2.26 s (3H, 4′-CH3), 2.39 br.s (6H, 2′-CH3, 6′-CH3),
2.48 d.d (1H, 6-H, J = 15.7, 3.8 Hz), 2.64 br.d (1H,
4-H, J = 16.9 Hz), 2.87–2.95 m (1H, 4-H), 3.09 d.d
(1H, 6-H, J = 15.4, 14.6 Hz), 3.23–3.42 m (4H,
NCH2), 3.73 m (1H, 5-H), 5.96 s (2H, OCH2O), 6.78 d
(1H, 5″-H, J = 8.0 Hz), 6.88 s (2H, 3′-H, 5′-H),
7.07 d.d (1H, 6″-H, J = 8.0, 1.5 Hz), 7.15 d (1H, 2″-H,
J = 1.5 Hz), 7.42 d (1H, CH=CHAr, J = 15.7 Hz),
7.49 d (1H, CH=CHAr, J = 15.7 Hz). Found, %:
C 76.56; H 7.01; N 2.88. m/z 472 (A) [M + 1]+.
C30H33NO4. Calculated, %: C 76.41; H 7.05; N 2.97.
M 471.60.
2-[(E)-3-(1,3-Benzodioxol-5-yl)prop-2-enoyl]-3-
(4-methylphenylamino)-5-(2,4,6-trimethylphenyl)-
cyclohex-2-en-1-one (Vn). Yield 87%, mp 203–
205°C. IR spectrum, ν, cm–1: 1635 s, 1545 v.s, 1510 m,
1500 m, 1490 m, 1445 s, 1240 v.s. 1H NMR spectrum,
δ, ppm: 2.22 s (3H, 4′-CH3), 2.33 s (9H, 2′-CH3,
6′-CH3, 4″-CH3), 2.65 m (2H, 4-H, 6-H), 3.07–3.19 m
(2H, 4-H, 6-H), 3.71 m (1H, 5-H), 5.99 s (2H,
OCH2O), 6.80 d (1H, 5′′′-H, J = 8.0 Hz), 6.82 s (2H,
3′-H, 5′-H), 7.04 d (2H, 2″-H, 6″-H, J = 8.1 Hz),
7.10 d.d (1H, 6′′′-H, J = 8.0, 1.0 Hz), 7.17 d (1H, 3″-H,
5″-H, J = 8.1 Hz), 7.20 d (1H, 2′′′-H, J = 1.0 Hz),
7.62 d (1H, CH=CHAr, J = 15.6 Hz), 7.96 d (1H,
CH=CHAr, J = 15.6 Hz), 14.25 br.s (1H, NH).
13C NMR spectrum, δC, ppm: 20.56 q, 20.56 q,
20.99 q, 21.99 q, 32.60 t, 34.11 d, 42.74 t, 101.37 t,
2-Aryl-1,2,3,4,5,6,7,8-octahydroquinoline-4,5-di-
ones VIa–VIg (general procedure). A solution of
2 mmol of enaminodiketone Va, Vb, Vf, Vh, Vj, Vm,
or Vn in 15 ml of anhydrous toluene was heated for
6–8 h under reflux with protection from atmospheric
moisture. The solutions containing dimedone deriva-
tives Va, Vb, Vf, Vh, and Vj were left to stand over-
night for crystallization. The precipitate of quinoline
derivative VIa–VIe was filtered off, washed with 5 ml
of toluene, and dried under reduced pressure. In the
case of mesityl-substituted compounds Vm and Vn,
quinolines VIf and Vg were isolated from the toluene
solution by column chromatography on silica gel using
chloroform–ethanol as eluent.
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SYNTHESIS OF EXO- AND ENDOCYCLIC ENAMINO DERIVATIVES
329
1-(4-Methoxyphenyl)-7,7-dimethyl-2-phenyl-
1,2,3,4,5,6,7,8-octahydroquinoline-4,5-dione (VIa).
Yield 67%, colorless crystals, mp 202–203°C. IR spec-
trum, ν, cm–1: 1685 v.s, 1610 m, 1580 v.s, 1260.
1H NMR spectrum, δ, ppm: 1.01 s and 1.03 s (3H each,
7-CH3), 2.25 m (2H, 6-H), 2.33 s (2H, 8-H), 2.78 br.d
(1H, 3-H, J = 15.6 Hz), 3.39 m (1H, 3-H), 3.81 s (3H,
CH3O), 4.92 m (1H, 2-H); 6.64 br.d, 6.73 br.d,
6.99 br.d, and 7.24 br.d (4H, C6H4, J = 6.3 Hz), 7.15–
7.20 m (2H, o-H), 7.25–7.33 m (3H, m-H, p-H).
Found, %: C 76.91; H 6.82; N 3.67. m/z 376 (A)
[M + 1]+. C24H25NO3. Calculated, %: C 76.77; H 6.71;
N 3.73. M 375.47.
1-(3,4-Dimethylphenyl)-2-(4-methoxyphenyl)-
7,7-dimethyl-1,2,3,4,5,6,7,8-octahydroquinoline-4,5-
dione (VId). Yield 72%, mp 182–185°C. IR spectrum,
1
ν, cm–1: 1680 s, 1610 m, 1510 v.s, 1240. H NMR
spectrum, δ, ppm: 1.00 s and 1.01 s (3H each, 7-CH3),
2.23 s (2H, 6-H), 2.27 s and 2.32 s (6H, 3′-CH3,
4′-CH3), 2.30 s (2H, 8-H), 2.75 d.d (1H, 3-H, J = 15.5,
2.3 Hz), 3.31 br.m (1H, 3-H), 3.77 s (3H, CH3O),
4.85 d.d (1H, 2-H, J = 7.5, 2.3 Hz), 6.43 d (1H, 6′-H,
J = 6.2 Hz), 6.78 d (2H, 3″-H, 5″-H, J = 7.9 Hz),
7.00 d (1H, 5′-H), 7.05 br.s (1H, 2′-H), 7.00 d (2H,
2″-H, 6″-H, J = 7.9 Hz). Found, %: C 77.50; H 7.27;
N 3.37. m/z 404 (A) [M + 1]+. C26H29NO3. Calculated,
%: C 77.39; H 7.24; N 3.47. M 403.52.
1-(3,4-Dimethylphenyl)-7,7-dimethyl-2-phenyl-
1,2,3,4,5,6,7,8-octahydroquinoline-4,5-dione (VIb).
Yield 75%, mp 215–216°C. IR spectrum, ν cm–1:
1670 s, 1520 v.s, 1500 v.s, 1450 m. 1H NMR spectrum,
δ, ppm: 1.01 s and 1.02 s (3H each, 7-CH3), 2.24 m
(2H, 6-H), 2.26 s (3H, 4′-CH3), 2.30 m (2H, 8-H),
2.32 br.s (3H, 3′-CH3), 2.75 d.d (1H, 3-H, J = 15.5,
2.8 Hz), 3.32 d.d (1H, 3-H, J = 15.5, 7.6 Hz), 4.90 d.d
(1H, 2-H, J = 7.6, 2.8 Hz); 6.48 br.s, 6.99 br.s, and
7.24 br.s (3H, C6H3); 7.12–7.20 m (2H, o-H), 7.23–
7.31 m (3H, m-H, p-H). 13C NMR spectrum, δC, ppm:
19.46 q, 19.86 q, 28.10 q, 28.40 q, 31.61 s, 43.64 t,
43.84 t, 51.65 t, 66.24 d, 109.15 s, 124.57 d, 126.83 d,
126.83 d, 127.92 d, 127.92 d, 128.48 d, 128.97 d,
128.97 d, 130.56 d, 137.68 s, 138.23 s, 140.35 s,
169.28 s, 186.55 s, 191.77 s. Found, %: C 80.51;
H 7.27; N 3.82. m/z 374 (A) [M + 1]+. C25H27NO2. Cal-
culated, %: C 80.40; H 7.29; N 3.75. M 373.50.
1,2-Bis(4-methoxyphenyl)-7,7-dimethyl-
1,2,3,4,5,6,7,8-octahydroquinoline-4,5-dione (VIe).
Yield 72%, mp 182–183°C. IR spectrum, ν, cm–1:
1690 m, 1660 m, 1610 w, 1510 v.s, 1500 v.s, 1440 m,
1
1250 s. H NMR spectrum, δ, ppm: 1.00 s (6H,
7-CH3), 2.18 m (2H, 6-H), 2.29 m (2H, 8-H), 2.74 br.d
(1H, 3-H, J = 15.4 Hz), 3.26 d.d (1H, 3-H, J = 15.4,
7.5 Hz), 3.76 s and 3.81 s (3H each, CH3O), 4.82 d.d
(1H, 2-H, J = 7.5, 3.2 Hz); 6.61 br.s, 6.73 br.s,
6.97 br.s, and 7.18 br.s (4H, NC6H4); 6.77 d (2H, 2′-H,
6′-H, J = 8.6 Hz), 7.07 d (2H, 3′-H, 5′-H, J = 8.6 Hz).
13C NMR spectrum, δC, ppm: 28.07 q, 28.41 q, 31.53 s,
43.82 t, 43.88 t, 51.62 t, 55.29 q, 55.53 q, 65.92 d,
108.99 s, 114.32 d, 114.32 d, 114.46 d, 115.45 d,
128.36 d, 128.36 d, 128.36 d, 128.84 d, 130.38 s,
135.23 s, 159.44 s, 159.64 s, 169.35 s, 186.84 s,
191.76 s. Found, %: C 74.15; H 6.82; N 3.35. m/z 406
(A) [M + 1]+. C25H27NO4. Calculated, %: C 74.05;
H 6.71; N 3.45. M 405.50.
2-(4-Methoxyphenyl)-7,7-dimethyl-1-(4-methyl-
phenyl)-1,2,3,4,5,6,7,8-octahydroquinoline-4,5-di-
one (VIc). Yield 70%, mp 171–172°C. IR spectrum, ν,
2-(1,3-Benzodioxol-5-yl)-1-(4-methoxyphenyl)-7-
(2,4,6-trimethylphenyl)-1,2,3,4,5,6,7,8-octahydro-
quinoline-4,5-dione (VIf). Yield 67%, oily substance.
IR spectrum, ν, cm–1: 1690 m, 1670 s, 1610 w,
1510 v.s, 1500 v.s, 1440 m, 1250 s. 1H NMR spectrum,
δ, ppm: 2.20 s (3H, 4′-CH3), 2.30 s (6H, 2′-CH3,
6′-CH3), 2.27–2.38 m (1H, 6-H), 2.53 d.d.d (0.6H,
8-H, J = 16.5, 3.9, 2.0 Hz), 2.57 d.d.d (0.4H, 8-H, J =
16.5, 4.5, 2.0 Hz), 2.77 d.d (0.6H, 6-H, J = 16.5,
2.5 Hz), 2.83 d.d (0.4H, 6-H, J = 16.5, 5.7 Hz), 2.88–
3.07 m (2H, 3-H), 3.17 d.d (0.4H, 8-H, J = 16.5,
6.7 Hz), 3.39 d.d (0.6H, 8-H, J = 16.5, 8.0 Hz), 3.64–
3.74 m (1H, 7-H), 3.75 s and 3.77 s (3H, CH3O), 4.82–
4.86 m (1H, 2-H), 5.92–5.97 m (2H, OCH2O), 6.55–
6.73 m (3H, Harom), 6.79 s (2H, Harom); 6.86 br.s,
6.93 br.s, 7.10 br.s, and 7.22 br.s (4H, Harom). Found,
%: C 75.35; H 6.27; N 2.61. m/z 510 (A) [M + 1]+.
1
cm–1: 1670 s, 1515 v.s, 1435 m, 1250 m. H NMR
spectrum, δ, ppm: 0.99 s and 1.00 s (3H each, 7-CH3),
2.18 m (2H, 6-H), 2.29 m (2H, 8-H), 2.37 s (3H,
4′-CH3), 2.75 d.d (1H, 3-H, J = 15.4, 3.2 Hz), 3.28 d.d
(1H, 3-H, J = 15.4, 7.5 Hz), 3.77 s (3H, CH3O),
4.83 d.d (1H, 2-H, J = 7.5, 3.2 Hz); 6.59 br.s, 7.00 br.s,
7.16 br.s, and 7.30 br.s (4H, Harom); 6.77 d (2H, 2″-H,
6″-H, J = 8.7 Hz), 7.07 d (2H, 3″-H, 5″-H, J = 8.7 Hz).
13C NMR spectrum, δC, ppm: 21.14 q, 28.08 q,
28.39 q, 31.59 s, 43.82 t, 43.87 t, 51.63 t, 55.29 q,
65.79 d, 109.04 s, 114.31 d, 114.31 d, 127.02 d,
127.36 d, 128.30 d, 128.30 d, 130.09 d, 130.35 s,
130.91 d, 138.96 s, 140.01 s, 159.63 s, 169.01 s,
186.80 s, 191.75 s. Found, %: C 75.56; H 6.27; N 2.82.
m/z 390 (A) [M + 1]+. C25H27NO3. Calculated, %:
C 77.09; H 6.99; N 3.60. M 389.50.
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RUBINOV et al.
330
2. Lakhvich, F.A. and Khlebnikova, T.S., Vestsi Akad.
Navuk BSSR, Ser. Khim. Navuk, 1996, no. 4, p. 114.
3. Baker, W., Grice, K.D., and Jansen, A.B., J. Chem. Soc.,
C32H31NO5. Calculated, %: C 75.42; H 6.13; N 2.75.
M 509.61.
2-(1,3-Benzodioxol-5-yl)-1-(4-methylphenyl)-7-
(2,4,6-trimethylphenyl)-1,2,3,4,5,6,7,8-octahydro-
quinoline-4,5-dione (VIg). Yield 69%, oily substance.
IR spectrum, ν, cm–1: 1690 m, 1670 s, 1610 w,
1943, p. 241.
4. Lakhvich, F.A., Pashkovskii, F.S., and Lis, L.G., Vestsi
Akad. Navuk BSSR, Ser. Khim. Navuk, 1987, no. 5,
p. 53.
1
1510 v.s, 1500 v.s, 1490 sh, 1440 m, 1250 s. H NMR
5. Henning, H.-G., Koppe, A., and Briehn, S., Pharmazie,
spectrum, δ, ppm (a mixture of diastereoisomers at C2
and C7 at a ratio of 7:3): 2.20 s (3H, 4′-CH3), 2.25–
2.34 m (9H, 2′-CH3, 6′-CH3, 4″-CH3), 2.25–2.32 m
(0.7H, 6-H), 2.37 d.d.d (0.3H, 6-H, J = 16.5, 3.5,
2.0 Hz), 2.52 d.d.d (0.7H, 8-H, J = 16.5, 3.5, 2.0 Hz),
2.358 d.d.d (0.3H, 8-H, J = 16.5, 4.5, 2.0 Hz), 2.77 d.d
(0.7H, 6-H, J = 16.5, 2.5 Hz), 2.88 d.d (0.3H, 6-H, J =
16.5, 5.5 Hz), 2.89–3.07 m (2H, 3-H), 3.20 d.d (0.3H,
8-H, J = 16.5, 7.0 Hz), 3.40 d.d (0.7H, 8-H, J = 16.5,
8.0 Hz), 3.64–3.75 m (1H, 7-H), 4.83–4.87 m (1H,
2-H), 5.92–5.97 m (2H, OCH2O), 6.55–6.73 m (3H,
1988, vol. 43, no. 7, p. 473.
6. Wiley, R.H., Jarboe, C.H., and Ellert, H.G., J. Am.
Chem. Soc., 1955, vol. 77, p. 5102.
7. Takeuchi, N., Nakagawa, H., and Tabinaga, S., Chem.
Pharm. Bull., 1980, vol. 28, p. 3002.
8. Lakhvich, F.A., Pashkovskii, F.S., and Lis, L.G., Vestsi
Akad. Navuk Belarusi, Ser. Khim. Navuk, 1993, no. 3,
p. 81.
9. Lakhvich, F.A., Pashkovskii, F.S., and Lis, L.G.,
Zh. Org. Khim., 1992, vol. 28, p. 1626.
10. Benary, E., Ber., 1913, vol. 46, p. 2103.
Harom), 6.79 s (2H, Harom); 7.00 br.s, 7.07 br.s, 7.19 br.s,
11. Rubinov, D.B., Budnikova, M.V., Zheldakova, T.A.,
Rubinova, I.L., Kuchuro, S.V., Babitskaya, S.V., and
Litvinko, N.M., Russ. J. Org. Chem., 2006, vol. 42,
p. 423.
and 7.24 br.s (4H, Harom). 13C NMR spectrum, δC, ppm:
major diastereoisomer: 20.53 q, 20.53 q, 21.06 q,
21.95 q, 34.34 d, 34.75 t, 42.25 t, 43.87 t, 66.10 d,
101.31 t, 107.26 d, 107.26 d, 108.53 d, 108.53 d,
109.20 s, 120.79 d, 120.79 d, 126.48 d, 130.08 s,
130.60 d, 131.31 d, 131.92 s, 134.38 s, 136.32 s,
136.44 s, 139.29 s, 139.52 s, 147.79 s, 148.09 s,
170.30 s, 186.77 s, 192.14 s; minor diastereoisomer:
20.53 q, 20.53 q, 21.06 q, 21.88 q, 34.64 d, 34.81 t,
41.95 t, 43.97 t, 65.86 d, 101.36 t, 107.11 d, 107.11 d,
108.53 d, 108.53 d, 110.24 s, 120.72 d, 120.72 d,
126.58 d, 127.63 s, 130.08 s, 130.60 d, 131.31 d,
131.82 s, 134.38 s, 136.29 s, 138.97 s, 139.79 s,
147.75 s, 148.19 s, 170.76 s, 187.29 s, 192.45 s.
Found, %: C 77.76; H 6.27; N 2.87. m/z 494 (A)
[M + 1]+. C32H31NO4. Calculated, %: C 77.87; H 6.33;
N 2.84. M 493.61.
12. Lakhvich, F.A., Lis, L.G., Rubinov, D.B., Rubino-
va, I.L., Kurbako, V.Z., and Bykhovets, A.I., Vestsi
Akad. Navuk BSSR, Ser. Khim. Navuk, 1989, no. 1,
p. 51.
13. Matsuzawa, M., Hokari, H., Kusano, S., Miyazawa, T.,
and Toyokawa, Y., EU Patent Appl. no. 199658, 1986;
Chem. Abstr., 1987, vol. 107, no. 35141b.
14. Kishida, M., Asami, T., Yoshida, S., Inoue, Y., and
Takahashi, N., JPN Patent Appl. no. 12-72561, 1989;
Chem. Abstr., 1990, vol. 112, no. 217309y.
15. Rubinov, D.B., Rubinova, I.L., and Akhrem, A.A.,
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 3 2011