Five-membered 2,3-dioxo heterocycles: LXV. Reaction of 1-methyl-3,4- dihydroisoquinolines with aroylketenes. crystalline and molecular structure of (1Z,3Z)-4-hydroxy-1-[6,7-dimethoxy-3,3-dimethyl-3,4-dihydroisoquinolin-1(2H) -ylidene]-4-phenylbut-3-en-2-o

Article abstract of DOI:10.1134/S1070428009100157

Aroylketenes generated in situ by thermolysis of 6-aryl-2,2-dimethyl-4H-1, 3-dioxin-4-ones reacted with 3,3-dialkyl-1-methyl-3,4-dihydroisoquinolines to give (1Z,3Z)-4-aryl-4-hydroxy-1-[3,3-dialkyl-3,4-dihydroisoquinolin-1(2H)- ylidene]but-3-en-4-ones. Th

Full text of DOI:10.1134/S1070428009100157

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 10, pp. 1515–1518. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © V.V. Khalturina, Yu.V. Shklyaev, Z.G. Aliev, A.N. Maslivets, 2009, published in Zhurnal Organicheskoi Khimii, 2009, Vol. 45,
No. 10, pp. 1531–1534.
Five-Membered 2,3-Dioxo Heterocycles: LXV.* Reaction
of 1-Methyl-3,4-dihydroisoquinolines with Aroylketenes.
Crystalline and Molecular Structure of (1Z,3Z)-4-Hydroxy-
1-[6,7-dimethoxy-3,3-dimethyl-3,4-dihydroisoquinolin-
1(2H)-ylidene]-4-phenylbut-3-en-2-one
V. V. Khalturinaa, Yu. V. Shklyaeva, Z. G. Alievb, and A. N. Maslivetsc
a Institute of Technical Chemistry, Ural Division, Russian Academy of Sciences, Perm, Russia
b Institute of Chemical Physics Problems, Russian Academy of Sciences, Chernogolovka, Moscow oblast, Russia
c Perm State University, ul. Bukireva 15, Perm, 614990 Russia
e-mail: koh2@psu.ru
Received October 27, 2008
Abstract—Aroylketenes generated in situ by thermolysis of 6-aryl-2,2-dimethyl-4H-1,3-dioxin-4-ones reacted
with 3,3-dialkyl-1-methyl-3,4-dihydroisoquinolines to give (1Z,3Z)-4-aryl-4-hydroxy-1-[3,3-dialkyl-3,4-dihy-
droisoquinolin-1(2H)-ylidene]but-3-en-4-ones. The crystalline and molecular structure of (1Z,3Z)-4-hydroxy-
1-[6,7-dimethoxy-3,3-dimethyl-3,4-dihydroisoquinolin-1(2H)-ylidene]-4-phenylbut-3-en-2-one was studied by
X-ray diffraction.
DOI: 10.1134/S1070428009100157
with enamines of the isoquinoline series, in the present
communication we report on the reaction of 6-aryl-
2,2-dimethyl-4H-1,3-dioxin-4-ones Ia and Ib with
1-methyl-3,4-dihydroisoquinolines IIa–IId.
5-Arylfuran-2,3-diones are known to undergo ther-
mal decarbonylation to give aroylketenes which are
capable of participating in cycloaddition reactions with
active dienophiles [2, 3] and acylating weak nucleo-
philes with formation of aroylacetyl derivatives [2, 4].
On the other hand, furandiones can acylate nucleo-
philic reagents to produce aroylpyruvoyl derivatives at
a temperature lower than that required for generation
of aroylketenes [2, 5]. We previously described reac-
tions of 5-arylfuran-2,3-diones with 1-methyl-3,4-di-
hydroisoquinolines, which led to the formation of
β-acylation products of the corresponding enamino
tautomers, (2Z,5Z)-1-aryl-3-hydroxy-5-[3,3-dialkyl-
3,4-dihydroisoquinolin-1(2H)-ylidene]pent-2-ene-1,4-
diones whose structure was proved by X-ray analysis
[1]. It is known that 6-aryl-2,2-dimethyl-4H-1,3-di-
oxin-4-ones [6] ([4+2]-cycloaddition products of
aroylketenes with acetone) undergo retro-Diels–Alder
reaction with generation of aroylketenes [7].
The reactions were carried out by heating equi-
molar amounts of compounds I and II in boiling
anhydrous toluene for 60–90 min, the progress of the
reactions being monitored by chromatography. As
a result, we isolated in good yields the corresponding
(1Z,3Z)-4-aryl-4-hydroxy-1-[3,3-dialkyl-3,4-dihydro-
isoquinolin-1(2H)-ylidene]-but-3-en-2-ones IIIa–IIIg.
Presumably, the reaction involves acylation of the
β-CH group in enamino tautomer A of isoquinolines
IIa–IId with aroylketene IV generated by thermal
decomposition of 6-aryl-2,2-dimethyl-4H-1,3-dioxin-
4-ones (via elimination of acetone molecule). The
structure of compound IIIe was proved by X-ray
analysis.
Compounds IIIa–IIIg are yellow crystalline or oily
substances, which are readily soluble in dimethyl
sulfoxide and dimethylformamide, poorly soluble in
common organic solvents, and insoluble in water and
alkanes; the products gave a positive color test (cherry
In continuation of our studies on reactions of dioxo
heterocycles and heterocumulenes derived therefrom
* For communication LXIV, see [1].
1515

KHALTURINA et al.
1516
Scheme 1.
O
O
O
·
Δ
O
–Me2CO
Me
Me
Ar
Ar
O
Ia, Ib
IV
R2
R3
R2
R3
R1
R1
R1
R1
N
NH
Me
CH2
IIa–IId
A
R2
R2
R3
R3
N
H
N
H
·
·
·
IV
·
·
R1
O
H
R1
· O
···
O
O
R1
R1
Ar
Ar
B
IIIa–IIIg
C
I, Ar = Ph (a), 4-MeC6H4 (b); II, R1 = H, R2 = R3 = Me (a); R2 = Me , R3 = Bu (b); R1 = MeO, R2 = R3 = Me (c); R1 = EtO, R2 = R3 =
Me (d); III, R1 = H, R2 = R3 = Me, Ar = Ph (a), 4-MeC6H4 (b); R2 = Me, R3 = Bu, Ar = Ph (c), 4-MeC6H4 (d); R1 = MeO, R2 = R3 =
Me, Ar = Ph (e), 4-MeC6H4 (f); R1 = EtO, R2 = R3 = Me, Ar = Ph (g).
color) for enolic hydroxy group with an alcoholic solu-
tion of iron(III) chloride.
rings and substituents therein, a six-proton singlet at
δ 1.27–1.28 ppm from two methyl groups in position 3
of the isoquinoline ring (IIIa, IIIb, IIIe–IIIg) or
a three-proton singlet at δ 1.27 ppm and signals at
δ 0.96–1.22 ppm from nine protons in the 3-methyl
and 3-butyl groups (IIIc, IIId), a two-proton singlet at
δ 2.82–2.91 ppm from the methylene protons on C4
in the isoquinoline ring, and singlets at δ 5.67–5.77
(1-H), 6.18–6.28 (3-H), 10.42–10.57 (NH), and 16.04–
16.07 ppm (OH, enol tautomer B). In addition, minor
signals assignable to diketone tautomer C were pres-
ent, the most characteristic of which were those
located at δ 4.00–4.10 (2H, 3-H) and 10.95–11.08 ppm
(1H, NH). In keeping with the signal intensity ratios,
compounds IIIa–IIIg in DMSO-d6 exist as mixtures of
enol and ketone tautomers B and C at a ratio of ~9:1.
The IR spectra of IIIa–IIIg contained broadened
absorption bands due to stretching vibrations of OH
and NH groups involved in intramolecular hydrogen
bond (3384–3417 cm–1) and H-bonded carbonyl group
(1582–1591 cm–1). Compounds IIIa–IIIg displayed in
1
the H NMR spectra signals from protons in aromatic
C13
C22
O3
C23
C21
C20
O4
C6
C4
C5
C12
C18
C3
C2
C16
C14
C19
C17
O2
C15
C7
C8
Figure shows the structure of molecule IIIe deter-
mined by X-ray analysis. Compound IIIe crystallizes
as a 2:1 solvate with toluene, which includes two
independent molecules. All bond lengths and bond
angles in the two crystallographically independent
molecules are equal within experimental error, and
they coincide with the corresponding parameters of
structurally related (2Z,5Z)-3-hydroxy-5-{8,8-dimeth-
yl-2,3,8,9-tetrahydro[1,4]dioxino[2,3-g]isoquinolin-
N1
O1
H2
C9
H1
C10
C11
Structure of the molecule of (1Z,3Z)-1-[6,7-dimethoxy-3,3-
dimethyl-3,4-dihydroisoquinolin-1(2H)-ylidene]-4-hydroxy-
4-phenylbut-3-en-2-one (IIIe) according to the X-ray dif-
fraction data.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 10 2009

FIVE-MEMBERED 2,3-DIOXO HETEROCYCLES: LXV.
1517
(3H, MeC6H4), 2.91 s (2H, 4′-H), 5.74 s (1H, 1-H),
6.22 s (1H, 3-H), 7.27–7.85 m (8H, C6H4), 10.47 s
(1H, NH), 16.05 s (1H, OH); C: 1.20 s (6H, Me), 2.37 s
(3H, MeC6H4), 2.86 s (2H, 4′-H), 4.04 s (2H, 3-H),
5.84 s (1H, 1-H), 7.22–7.93 m (8H, C6H4), 11.01 s
(1H, NH). Found, %: C 79.24; H 7.15; N 4.02.
C22H23NO2. Calculated, %: C 79.25; H 6.95; N 4.20.
6(7H)-ylidene}-1-phenylpent-2-ene-1,4-dione [1].
Molecules IIIe in crystal are stabilized by two strong
intramolecular hydrogen bonds O2–H2 ···O1 and
N–H···O1. Their parameters are given below.
D–H···A
d(D–H) d(H···A) ∠DHA d(D···A)
O2–H2 ···O1
1.089
1.208
1.043
0.992
1.458
1.368
1.720
1.786
153.99
148.40
140.86
140.93
2.483
2.478
2.613
2.632
(1Z,3Z)-1-[3-Butyl-3-methyl-3,4-dihydroiso-
quinolin-1(2H)-ylidene]-4-hydroxy-4-phenylbut-3-
en-2-one (IIIc). Yield 84%, oily substance. IR spec-
trum, ν, cm–1: 3385 br (NH, OH), 1584 br (CO).
1H NMR spectrum, δ, ppm: B: 0.98 t (3H, CH3CH2,
J = 7.0 Hz), 1.14–1.22 m (6H, CH2CH2CH2), 1.27 s
(3H, 3-CH3), 2.84 s (2H, 4′-H), 5.70 s (1H, 1-H),
6.24 s (1H, 3-H), 7.45–8.03 m (9H, Harom), 10.57 s
(1H, NH), 16.06 s (1H, OH); C: 0.91 t (3H, CH3CH2,
J = 7.0 Hz), 1.08–1.16 m (6H, CH2CH2CH2), 1.24 s
(3H, 3-CH3), 2.78 s (2H, 4′-H), 4.06 s (2H, 3-H),
5.79 s (1H, 1-H), 7.39–7.97 m (9H, Harom), 11.08 s (1H,
NH). Found, %: C 79.68; H 7.53; N 3.70. C24H27NO2.
Calculated, %: C 79.74; H 7.53; N 3.87.
N–H···O1
It is seen that both intramolecular hydrogen bonds
are characterized by similar parameters. The C15=O1
bond length is 1.292 Å in both molecules, i.e., it is
appreciably extended. Thus compound IIIe in crystal
has the structure of enol tautomer B.
EXPERIMENTAL
The IR spectra were recorded on an FSM-1201
spectrometer from samples dispersed in mineral oil.
1
The H and 13C NMR spectra were measured on
(1Z,3Z)-1-[3-Butyl-3-methyl-3,4-dihydro-
isoquinolin-1(2H)-ylidene]-4-hydroxy-4-(4-methyl-
phenyl)but-3-en-2-one (IIId). Yield 85%, mp 164–
166°C (decomp., from petroleum ether). IR spectrum,
1
a Bruker AM-400 instrument (400 MHz for H) from
solutions in DMSO-d6 using tetramethylsilane as inter-
nal reference. The purity of the isolated compounds
was checked by thin-layer chromatography on Silufol
plates using ethyl acetate–benzene (1:5) or ethyl ace-
tate as eluent; development with iodine vapor.
1
ν, cm–1: 3384 br (NH, OH), 1582 br (CO). H NMR
spectrum, δ, ppm: B: 0.96 t (3H, CH3CH2, J = 7.0 Hz),
1.15–1.21 m (6H, CH2CH2CH2), 1.27 s (3H, 3-CH3),
2.35 s (3H, MeC6H4), 2.84 s (2H, 4′-H), 5.67 s (1H,
1-H), 6.18 s (1H, 3-H), 7.26–7.77 m (8H, C6H4),
10.51 s (1H, NH), 16.04 s (1H, OH); C: 0.90 t (3H,
CH3CH2, J = 7.0 Hz), 1.09–1.15 m (6H, CH2CH2CH2),
1.24 s (3H, 3-CH3), 2.37 s (3H, MeC6H4), 2.79 s (2H,
4′-H), 4.00 s (2H, 3-H), 5.76 s (1H, 1-H), 7.23–7.91 m
(8H, C6H4), 11.07 s (1H, NH). Found, %: C 79.85;
H 7.83; N 3.59. C25H29NO2. Calculated, %: C 79.96;
H 7.78; N 3.73.
(1Z,3Z)-1-[3,3-Dimethyl-3,4-dihydroisoquinolin-
1(2H)-ylidene]-4-hydroxy-4-phenylbut-3-en-2-one
(IIIa). A solution of 2.0 mmol of 2,2-dimethyl-6-
phenyl-4H-1,3-dioxin-4-one (Ia) and 2.0 mmol of iso-
quinoline (IIa) in 20 ml of anhydrous toluene was
heated for 60 min under reflux. The mixture was
cooled, and the precipitate was filtered off. Yield
0.60 g (85%), oily substance. IR spectrum, ν, cm–1:
1
3385 br (NH, OH), 1587 br (CO). H NMR spectrum,
δ, ppm: B: 1.28 s (6H, Me), 2.91 s (2H, 4′-H), 5.77 s
(1H, 1-H), 6.28 s (1H, 3-H), 7.31–8.04 m (9H, Harom),
10.53 s (1H, NH), 16.07 s (1H, OH); C: 1.20 s (6H,
Me), 2.86 s (2H, 4′-H), 4.10 s (2H, 3-H), 5.87 s (1H,
1-H), 7.28–7.98 m (9H, Harom), 11.02 s (1H, NH).
Found, %: C 78.82; H 6.75; N 4.20. C21H21NO2. Cal-
culated, %: C 78.97; H 6.63; N 4.39.
(1Z,3Z)-1-[6,7-Dimethoxy-3,3-dimethyl-3,4-dihy-
droisoquinolin-1(2H)-ylidene]-4-hydroxy-4-phenyl-
but-3-en-2-on (IIIe). Yield 87%, mp 142–143°C
(decomp., from ethyl acetate). IR spectrum, ν, cm–1:
1
3385 br (NH, OH), 1589 br (CO). H NMR spectrum,
δ, ppm: B: 1.28 s (6H, Me), 2.84 s (2H, 4′-H), 3.84 s
and 3.86 s (3H each, OMe), 5.74 s (1H, 1-H), 6.23 s
(1H, 3-H), 6.91 s and 7.33 s (1H each, 5′-H, 8′-H),
7.46–7.48 m (3H, Harom), 7.79–7.81 m (2H, Harom),
10.47 s (1H, NH), 16.06 s (1H, OH); C: 1.20 s (6H,
Me), 2.78 s (2H, 4′-H), 3.82 s and 3.83 s (3H each,
OMe), 4.07 s (2H, 3-H), 5.82 s (1H, 1-H), 6.89 s and
7.27 s (1H each, 5′-H, 8′-H), 7.61–7.63 m (3H, Harom),
8.01–8.03 m (2H, Harom), 10.97 s (1H, NH). Found, %:
Compounds IIIb–IIIg were synthesized in a sim-
ilar way.
(1Z,3Z)-1-[3,3-Dimethyl-3,4-dihydroisoquinolin-
1(2H)-ylidene]-4-hydroxy-4-(4-methylphenyl)but-3-
en-2-one (IIIb). Yield 86%, oily substance. IR spec-
trum, ν, cm–1: 3386 br (NH, OH), 1585 br (CO).
1H NMR spectrum, δ, ppm: B: 1.27 s (6H, Me), 2.35 s
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 10 2009

KHALTURINA et al.
1518
C 72.68; H 6.84; N 3.67. C23H25NO4. Calculated, %:
C 72.80; H 6.64; N 3.69.
(1Z,3Z)-1-[6,7-Diethoxy-3,3-dimethyl-3,4-dihy-
droisoquinolin-1(2H)-ylidene]-4-hydroxy-4-phenyl-
but-3-en-2-one (IIIg). Yield 89%, mp 133–135°C
(decomp., from ethanol). IR spectrum, ν, cm–1: 3385 br
X-Ray diffraction study of compound IIIe. Com-
pound IIIe crystallized as a 2:1 solvate with toluene.
Yellow crystals, C23H25NO4 ·0.5C6H5CH3, triclinic
crystal system., space group P-1. Unit cell parameters:
a = 11.444(2), b = 12.919(2), c = 17.669(2) Å; α =
76.56(1), β = 87.32(1), γ = 70.62(1)°; V =
2395.5(6) Å3; M 425.51; dcalc = 1.180 g/cm3; Z = 4.
A set of experimental reflection intensities was ac-
quired on a KM-4 automatic four-circle diffractometer
with χ geometry (monochromatized MoKα irradiation,
ω/2Θ scannong, 2Θmax = 50°, 89.6% of possible reflec-
tion number). Total of 7578 independent reflections
were measured (Rint = 0.0192), 3695 of which were
with I ≥ 2σ(I). No correction for absorption was intro-
duced (μ = 0.079 mm–1). The structure was solved by
the direct method using SIR92 program [8], followed
by a series of calculation of electron density maps. The
positions of all hydrogen atoms, except for H1 and H2,
were set on the basis of geometry considerations. The
H1 and H2 atoms were localized objectively from the
difference synthesis of electron density. The molecule
of toluene was refined with fixed geometry because of
large dispersion of bond lengths. The refinement by the
least-squares procedure in full-matrix anisotropic ap-
proximation (SHELXL-97 [9]) was terminated at R1 =
0.0671, wR2 = 0.1804 [3695 reflections with I ≥ 2σ(I)]
and at R1 = 0.1455, wR2 = 0.2314 (all reflections);
goodness of fit 1.022.
1
(NH, OH), 1584 br (CO). H NMR spectrum, δ, ppm:
B: 1.27 s (6H, Me), 1.34–1.38 m (6H, CH3CH2O),
2.82 s (2H, 4′-H), 4.08–4.14 m (4H, CH2O), 5.71 s
(1H, 1-H), 6.23 s (1H, 3-H), 6.89 s and 7.32 s (1H
each, 5′-H, 8′-H), 7.46–7.48 m (3H, Harom), 7.79–
7.81 m (2H, Harom), 10.45 s (1H, NH), 16.05 s (1H,
OH); C: 1.19 s (6H, Me), 1.41–1.44 (6H, CH3CH2O),
2.76 s (2H, 4′-H), 4.07 s (2H, 3-H), 4.16–4.18 m (4H,
CH2O), 5.79 s (1H, 1-H), 6.87 s and 7.23 s (1H each,
5′-H, 8′-H), 7.61–7.63 m (3H, Harom), 8.01–8.03 m (2H,
H
arom), 10.95 s (1H, NH). 13C NMR spectrum, δC, ppm:
14.60 and 14.73 (CH3CH2), 27.74 (3-CH3), 49.57 (C4′),
63.85 and 64.18 (CH2O), 88.87 (C3′), 98.00 (C3),
110.40 (C1), 112.88–151.38 (Carom), 156.08 (C1′), 167.78
(C4), 189.21 (C2). Found, %: C 73.61; H 7.25; N 3.43.
C25H29NO4. Calculated, %: C 73.69; H 7.17; N 3.44.
This study was performed under financial support
by the Russian Foundation for Basic Research (project
nos. 08-03-01032, 07-03-00001).
REFERENCES
1. Khalturina, V.V., Shklyaev, Yu.V., Aliev, Z.G., and Mas-
livets, A.N., Russ. J. Org. Chem., 2009, vol. 45, p. 728.
2. Andreichikov, Yu.S., Gein, V.L., Zalesov, V.V., Koz-
lov, A.P., Kollents, G., Maslivets, A.N., Pimenova, E.V.,
and Shurov, S.N., Khimiya pyatichlennykh 2,3-diokso-
geterotsiklov (Chemistry of Five-Membered 2,3-Dioxo
Heterocycles), Perm: Perm. Univ., 1994, p. 5.
3. Nekrasov, D.D. and Shurov, S.N., Khim. Geterotsikl.
Soedin., 2005, p. 1245.
4. Novikov, A.A., Vostrov, E.S., and Maslivets, A.N., Russ.
J. Org. Chem., 2005, vol. 41, p. 1234.
5. Andreichikov, Yu.S., Voronova, L.A., and Milyutin, A.V.,
Zh. Org. Khim., 1979, vol. 15, p. 847.
6. Andreichikov, Yu.S., Gein, L.F., and Plakhina, G.D.,
Zh. Org. Khim., 1980, vol. 16, p. 2336.
7. Vostrov, E.S., Novikov, A.A., Maslivets, A.N., and
Aliev, Z.G., Russ. J. Org. Chem., 2007, vol. 43, p. 224.
8. Altomare, A., Cascarano, G., Giacovazzo, C., and
(1Z,3Z)-1-[6,7-Dimethoxy-3,3-dimethyl-3,4-di-
hydroisoquinolin-1(2H)-ylidene]-4-hydroxy-4-
(4-methylphenyl)but-3-en-2-one (IIIf). Yield 88%,
mp 139–141°C (decomp., from ethyl acetate). IR spec-
trum, ν, cm–1: 3417 br (NH, OH), 1591 br (CO).
1H NMR spectrum, δ, ppm: B: 1.27 s (6H, Me), 2.35 s
(3H, MeC6H4), 2.83 s (2H, 4′-H), 3.83 s and 3.85 s (3H
each, OMe), 5.72 s (1H, 1-H), 6.18 s (1H, 3-H), 6.91 s
(1H, 5′-H or 8′-H), 7.26–7.28 m (2H, C6H4), 7.32 s
(1H, 8′-H or 5′-H), 7.68–7.70 m (2H, C6H4), 10.42 s
(1H, NH), 16.06 s (1H, OH); C: 1.20 s (6H, Me), 2.37 s
(3H, MeC6H4), 2.78 s (2H, 4′-H), 3.82 s and 3.83 s (3H
each, OMe), 4.02 s (2H, 3-H), 5.81 s (1H, 1-H), 6.89 s
(1H, 5′-H or 8′-H), 7.23–7.26 m (2H, C6H4), 7.28 s
(1H, 8′-H or 5′-H), 7.90–7.92 m (2H, C6H4), 10.97 s
(1H, NH). Found, %: C 73.25; H 6.94; N 3.53.
C24H27NO4. Calculated, %: C 73.26; H 6.92; N 3.56.
Gualardi, A., J. Appl. Crystallogr., 1993, vol. 26, p. 343.
9. Sheldrick, G.M., SHELX-97. Programs for Crystal Struc-
ture Analysis, Göttingen, Germany: Univ. of Göttingen,
1998.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 10 2009