Synthesis of Podands of the 3,4-dihydroisoquinoline series

Article abstract of DOI:10.1134/S1070428014030130

Podands containing 3,4-dihydroisoquinoline fragments were synthesized by reactions of 1,1′-{ethane-1,2-diylbis[oxy(3-methoxybenzene-4,1-diyl)]} bis(2-methylpropan-1-ol) and 1-(2-ethoxyethoxy)-2-methoxy-4-(2-methylprop-1-en- 1-yl)benzene with ethyl cyanoacetate and methyl thiocyanate in concentrated sulfuric acid. Likewise, 1-substituted 3,4-dihydroisoquinolines having a crown ether fragment were obtained from 4-acetylbenzo-12-crown-4.

Full text of DOI:10.1134/S1070428014030130

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2014, Vol. 50, No. 3, pp. 376–380. © Pleiades Publishing, Ltd., 2014.
Original Russian Text © Yu.V. Shklyaev, T.S. Vshivkova, 2014, published in Zhurnal Organicheskoi Khimii, 2014, Vol. 50, No. 3, pp. 387–391.
Synthesis of Podands of the 3,4-Dihydroisoquinoline Series
Yu. V. Shklyaev and T. S. Vshivkova
Institute of Technical Chemistry, Ural Branch, Russian Academy of Sciences,
ul. Akademika Koroleva 3, Perm, 614013 Russia
e-mail: shklyaev@itch.perm.ru
Received July 17, 2013
Abstract—Podands containing 3,4-dihydroisoquinoline fragments were synthesized by reactions of
1,1′-{ethane-1,2-diylbis[oxy(3-methoxybenzene-4,1-diyl)]}bis(2-methylpropan-1-ol) and 1-(2-ethoxyethoxy)-
2-methoxy-4-(2-methylprop-1-en-1-yl)benzene with ethyl cyanoacetate and methyl thiocyanate in concentrated
sulfuric acid. Likewise, 1-substituted 3,4-dihydroisoquinolines having a crown ether fragment were obtained
from 4-acetylbenzo-12-crown-4.
DOI: 10.1134/S1070428014030130
Benzocrown ethers are widely used in organic and
coordination chemistry [1, 2]. Numerous attempts were
made to obtain heterocyclic compounds with both
fused crown ether fragment [3, 4] and that connected
through a rigid spacer [5]. Also, possible synthetic
routes to heterocyclic compounds containing polyether
chains, i.e., podands exhibiting interesting complexing
properties, were explored in many publications [6, 7].
Both crown-containing heterocyclic compounds
and podands are generally synthesized from function-
alized aromatic compounds [1, 2]. Following this
approach, we have synthesized 4-(2-ethoxyethoxy)-3-
methoxybenzaldehyde (I) by alkylation of vanillin
with 2-ethoxyethyl methanesulfonate, and the subse-
quent Grignard reaction of I gave 1-(2-ethoxyethoxy)-
2-methoxy-4-(2-methylprop-1-en-1-yl)benzene (II).
The latter was brought into reactions with ethyl cyano-
acetate, acetonitrile, and methyl thiocyanate to obtain
the corresponding 3,4-dihydroisoquinoline derivatives
IIIa–IIIc (Scheme 1).
An interesting pattern was observed in the synthesis
of the corresponding carbinol from 4,4′-[ethane-1,2-
diylbis(oxy)]bis(3-methoxybenzaldehyde) (IV). Ad-
dition of the latter to isopropylmagnesium bromide
afforded both the expected product, 1,1′-{ethane-1,2-
diylbis[oxy(3-methoxybenzene-4,1-diyl)]}bis(2-meth-
ylpropan-1-ol) (VI), and 1,1′-{ethane-1,2-diylbis[oxy-
(3-methoxybenzene-4,1-diyl)]}bis(2-methylpropan-1-
one) (V) at a ratio of 1:1. Presumably, compound V
was formed via Meerwein–Ponndorf–Verley-like reac-
tion [8]. We failed to separate compounds V and VI by
column chromatography, but the reduction of mixture
V/VI with sodium tetrahydridoborate in ethanol
afforded alcohol VI whose reactions with ethyl cyano-
Scheme 1.
Me
Me
MeO
O
NCCH2COOEt
EtO
EtO
NH
COOEt
MeO
O
Me
IIIa
EtO
Me
Me
Me
MeO
O
II
RCN
N
R
IIIb, IIIc
R = Me (b), MeS (c).
376

SYNTHESIS OF PODANDS OF THE 3,4-DIHYDROISOQUINOLINE SERIES
377
Scheme 2.
OMe
MeO
OMe
MeO
O
O
HO
OH
NaBH4
O
O
O
O
Me
Me
Me
Me
Me
Me
Me
MeO
Me
V
VI
OMe
O
O
2NCCH2COOEt
Me
Me
Me
Me
HN
EtOC(O)
NH
COOEt
VIIa
VIIb
OMe
MeO
2MeSCN
O
O
Me
Me
Me
Me
N
N
SMe
MeS
Scheme 3.
Me
O
HO
Me
Me
Me
Me
O
O
O
O
O
O
O
O
O
O
O
O
NCCH2COOEt
Me
Me
NH
COOEt
VIIIa
H+
MeSCN
Me
Me
Me
Me
Me
Me
Me
O
O
O
O
O
O
O
O
N
N
SMe
VIIIc
VIIIb
Scheme 4.
Me
EtO
O
O
EtO
EtO
O
O
Me
+
Me
OEt
O
Me
NC
+
NH
CHO
EtO
COOEt
IX
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 3 2014

SHKLYAEV, VSHIVKOVA
378
acetate and methyl thiocyanate produced the corre-
sponding 3,4-dihydroisoquinoline derivatives VIIa and
VIIb (Scheme 2). Likewise, crown-containing com-
pounds VIIIa–VIIIc were obtained from 4-acetyl-
benzo-12-crown-4 (Scheme 3).
Podands containing a 3,4-dihydroisoquinoline frag-
ment can also be synthesized via three-component
condensation [9]. For instance, the reaction of 1,2-bis-
(2-ethoxyethoxy)benzene with isobutyraldehyde and
ethyl cyanoacetate in 96% sulfuric acid gave ethyl
2-[6,7-bis(2-ethoxyethoxy)-3,3-dimethyl-3,4-dihydro-
isoquinolin-1(2H)-ylidene]ethanoate (IX) (Scheme 4).
CHO). Mass spectrum, m/z (Irel, %): 224 (38) [M]+,
152 (21), 151 (39). Found, %: C 63.99; H 7.31.
C12H16O4. Calculated, %: C 64.27; H 7.19. M 224.25.
1-(2-Ethoxyethoxy)-2-methoxy-4-(2-methylprop-
1-en-1-yl)benzene (II). Yield 48%, bp 163–165°C
(6 mm). IR spectrum, ν, cm–1: 2980, 2945, 2882, 2859,
1
1513. H NMR spectrum, δ, ppm: 1.21 t (3H,
OCH2Me, J = 6.9 Hz), 1.85 d and 1.86 d (3H each,
Me, J = 6.3 Hz), 3.58 q (2H, OCH2, J = 7.05 Hz),
3.78–3.84 m (2H, OCH2), 3.82 s (3H, OMe), 4.15 t
(2H, OCH2, J = 5.25 Hz), 6.19 s (1H, CH), 6.74–
6.76 m (2H, Harom), 6.84–6.87 m (1H, Harom). Mass
spectrum, m/z (Irel, %): 250 (83) [M]+, 178 (100), 163
(23), 131 (26). Found, %: C 71.78; H 8.62. C15H22O3.
Calculated, %: C 71.97; H 8.86. M 250.33.
EXPERIMENTAL
The melting points were determined on a PTP
melting point apparatus. The IR spectra were recorded
on a Bruker IFS-66 spectrometer from solutions in
chloroform (II, IIIa–IIIc, VI, VIIb) or Nujol mulls
(VIIIa–VIIIc, IX). The 1H and 13C NMR spectra were
measured on a Varian Mercury Plus 300 instrument at
300 and 75 MHz, respectively, using CDCl3 as solvent
and hexamethyldisiloxane as internal reference. The
mass spectra (electron impact, 70 eV) were obtained
on an Agilent Technologies 6890N/5975B GC/MS sys-
tem. Analysis of compounds IIIa and VIIIa revealed
products of their deethoxycarbonylation (compounds
IIIb and VIIIb, respectively), which were likely to be
formed due to thermolysis in the injector. The elemen-
tal compositins were determined on a Leco Corpora-
tion CHNS-932 analyzer. The progress of reactions
and the purity of products were monitored by TLC on
Sorbfil UV-254 plates using ethyl acetate and ethyl
acetate–hexane (1:1) as eluents; spots were visualized
by treatment with a 0.5% solution of chloranil in
toluene.
1-Substituted 3,4-dihydroisoquinolines IIIa–IIIc,
VIIa, VIIb, VIIIa, and VIIIc (general procedure).
A mixture of 0.01 mol of the correspondng alcohol or
alkenylbenzene and 0.01 mol of nitrile was added
dropwise to 5 mL of 96% sulfuric acid cooled to 5–
10°C. The mixture was stirred for 1.5 h at 20–25°C,
poured into water, and neutralized to pH 7–8 with
sodium carbonate. The product was extracted into
methylene chloride, the extract was washed with water
and dried over anhydrous MgSO4, the solvent was
distilled off, and the residue was purified by column
chromatography or recrystallization.
Ethyl 2-[7-(2-ethoxyethoxy)-6-methoxy-3,3-di-
methyl-3,4-dihydroisoquinolin-1(2H)-ylidene]-
ethanoate (IIIa). Yield 2.14 g (59%), light yellow
crystals, mp 92–93°C (from EtOH). IR spectrum, ν,
cm–1: 3274 (NH), 3189 (NH), 2972, 2933, 2870, 1647
1
(C=N), 1600, 1571, 1514. H NMR spectrum, δ, ppm:
1.21–1.31 m (6H, OCH2Me), 1.26 s (6H, Me), 2.74 s
(2H, CH2), 3.59 q (2H, OCH2, J = 7.0 Hz), 3.79–
3.80 m (2H, OCH2), 3.87 s (3H, OMe), 4.11–4.19 m
(4H, OCH2), 5.01 s (1H, CH), 6.60 s (1H, Harom),
7.22 s (1H, Harom), 8.91 br.s (1H, NH). 13C NMR spec-
trum, δC, ppm: 14.6, 15.0, 28.3, 41.5, 49.2, 55.7, 58.3,
66.7, 68.7, 68.8, 76.4, 76.6, 110.5, 111.4, 120.4,
129.1, 146.9, 151.6, 155.3, 171.0. Found, %: C 65.76;
H 7.96; N 3.59. C20H29NO5. Calculated, %: C 66.09;
H 8.04; N 3.85.
4-(2-Ethoxyethoxy)-3-methoxybenzaldehyde (I).
Vanillin, 0.1 mol, was added to a solution of 0.1 mol of
potassium hydroxide in 50 mL of dimethyl sulfoxide,
and the mixture was heated on a boiling water bath.
2-Ethoxyethyl methanesulfonate, 0.1 mol, was then
added, and the mixture was heated for 6 h at 40°C. The
mixture was washed with a solution of potassium
hydroxide and treated with diethyl ether, the extract
was washed with water and dried over Na2SO4, and
the solvent was distilled off. Yield 12.5 g (56%), oily
7-(2-Ethoxyethoxy)-6-methoxy-1,3,3-trimethyl-
3,4-dihydroisoquinoline (IIIb). Yield 1.07 g (37%),
light yellow crystals, mp 65–66°C (from hexane–
EtOAc). IR spectrum, ν, cm–1: 2977, 2939, 2917, 2868,
1
substance. H NMR spectrum, δ, ppm: 1.21 t (3H,
OCH2Me, J = 6.9 Hz), 3.59 q (2H, OCH2, J = 7.0 Hz),
3.84 t (2H, OCH2, J = 5.1 Hz), 3.90 s (3H, OMe),
4.24 t (2H, OCH2, J = 5.1 Hz), 7.38–7.43 m (2H,
1
1624 (C=N), 1604, 1571. H NMR spectrum, δ, ppm:
1.18 s (6H, Me), 1.23 t (3H, OCH2Me, J = 6.9 Hz),
H
arom), 7.00 d (1H, Harom, J = 8.1 Hz), 9.83 s (1H,
2.31 s (3H, Me), 2.60 s (2H, CH2), 3.60 q (2H, OCH2,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 3 2014

SYNTHESIS OF PODANDS OF THE 3,4-DIHYDROISOQUINOLINE SERIES
379
J = 6.9 Hz), 3.81 t (2H, OCH2, J = 5.1 Hz), 3.88 s (3H,
OMe), 4.19 t (2H, OCH2, J = 5.1 Hz), 6.63 s (1H,
Found, %: C 68.61; H 8.25. C24H34O6. Calculated, %:
C 68.87; H 8.19. M 418.52.
H
arom), 7.11 s (1H, Harom). 13C NMR spectrum, δC, ppm:
Diethyl 7,7′-[ethane-1,2-diylbis(oxy)]bis{[6-me-
thoxy-3,3-dimethyl-3,4-dihydroisoquinolin-1(2H)-
ylidene]ethanoate} (VIIa). Yield 1.16 g (19%), white
14.9, 23.1, 27.7, 38.3, 53.2, 55.5, 66.5, 68.8, 69.1,
111.0, 112.3, 121.1, 130.4, 146.2, 151.5, 160.3. Mass
spectrum, m/z (Irel, %): 291 (100) [M]+, 276 (42) [M –
Me]+, 218 (11), 204 (31). Found, %: C 69.76; H 8.43;
N 4.55. C17H25NO3. Calculated, %: C 70.07; H 8.65;
N 4.81. M 291.39.
1
crystals, mp 185°C (decomp.; from EtOH). H NMR
spectrum, δ, ppm: 1.24–1.31 m (18H, Me), 2.74 s (4H,
CH2), 3.88 s (6H, OMe), 4.14 q (4H, OCH2Me), 4.41 s
(4H, OCH2CH2O), 5.02 s (2H, CH), 6.61 s (2H, Harom),
7.25 s (2H, Harom), 8.92 br.s (2H, NH). Mass spectrum,
m/z (Irel, %): 464 (14) [M – 2CO2Et + 2H]+, 450 (30),
449 (100) [M – 2CO2Et + 2H – Me]+, 219 (16), 218
(22). Found, %: C 66.85; H 7.22; N 4.43. C34H44N2O8.
Calculated, %: C 67.09; H 7.29; N 4.60. M 608.72.
7-(2-Ethoxyethoxy)-6-methoxy-3,3-dimethyl-1-
methylsulfanyl-3,4-dihydroisoquinoline (IIIc). Yield
1.42 g (44%), white crystals, mp 54–55°C (from
EtOH). IR spectrum, ν, cm–1: 2968, 2925, 2870, 1596,
1
1563, 1512. H NMR spectrum, δ, ppm: 1.18 s (6H,
Me), 1.24 t (3H, OCH2Me, J = 7.0 Hz), 2.40 s (3H,
SMe), 2.61 s (2H, CH2), 3.60 q (2H, OCH2, J =
7.0 Hz), 3.82 t (2H, OCH2, J = 5.1 Hz), 3.87 s (3H,
OMe), 4.19 t (2H, OCH2, J = 5.1 Hz), 6.62 s (1H,
Harom), 7.23 s (1H, Harom). 13C NMR spectrum, δC,
ppm: 12.2, 15.1, 28.3, 38.9, 55.7, 55.9, 66.8, 68.8,
68.9, 110.7, 111.0, 121.2, 129.9, 146.5, 151.6, 159.4.
Mass spectrum, m/z (Irel, %): 323 (14) [M]+, 308 (100)
[M – Me]+, 250 (16). Found, %: C 62.90; H 7.71;
N 4.50; S 9.62. C17H25NO3S. Calculated, %: C 63.13;
H 7.79; N 4.33; S 9.91. M 323.45.
4,4′-[Ethane-1,2-diylbis(oxy)]bis(3-methoxy-
benzaldehyde) (IV) was synthesized by alkylation of
vanillin with methylene bromide in DMSO according
to [10]. Yield 47%, light yellow crystals, mp 179–
181°C; published data [10]: mp 169°C. 1H NMR spec-
trum, δ, ppm: 3.90 s (6H, OMe), 4.54 s (4H,
OCH2CH2O), 7.10 d (2H, Harom, J = 8.1 Hz), 7.41–
7.46 m (4H, Harom), 9.86 s (2H, CHO). Mass spectrum,
m/z (Irel, %): 330 (56) [M]+, 180 (11), 179 (100), 165
(12), 164 (22), 152 (15), 151 (48), 150 (13), 149 (32).
Found, %: C 65.16; H 5.25. C18H18O6. Calculated, %:
C 65.45; H 5.49. M 330.33.
1,1′-{Ethane-1,2-diylbis[oxy(3-methoxybenzene-
4,1-diyl)]}bis(2-methylpropan-1-ol) (VI). Yield 69%,
white crystals, mp 112–113°C. IR spectrum, ν, cm–1:
3432 br (OH), 2957, 2930, 2871, 1592, 1513. 1H NMR
spectrum, δ, ppm: 0.76 d (6H, Me, J = 7.2 Hz), 1.01 d
(6H, Me, J = 6.6 Hz), 1.88–1.95 m (4H, CH, OH),
3.85 s (6H, OMe), 4.27 d (2H, CH, J = 6.9 Hz), 4.40 s
(4H, OCH2), 6.80 d.d (2H, Harom, J = 8.1, 1.8 Hz),
6.87 d (2H, Harom, J = 1.8 Hz), 6.92 d (2H, Harom, J =
8.1 Hz). 13C NMR spectrum, δC, ppm: 18.4, 19.0, 35.2,
55.9, 67.6, 79.9, 110.2, 118.9, 137.3, 147.4, 149.5.
Mass spectrum, m/z (Irel, %): 418 (31) [M]+, 382 (28),
357 (100), 205 (43), 190 (26), 179 (72), 178 (21).
7,7′-[Ethane-1,2-diylbis(oxy)]bis[6-methoxy-3,3-
dimethyl-1-(methylsulfanyl)-3,4-dihydroisoquino-
line] (VIIb). Yield 0.74 g (14%), light yellow crystals,
mp 196–197°C (from EtOH). IR spectrum, ν, cm–1:
1
2958, 2921, 2851, 1597, 1514. H NMR spectrum, δ,
ppm: 1.24 s (12H, Me), 2.41 s (6H, SMe), 2.62 s (4H,
CH2), 3.87 s (6H, OMe), 4.43 s (4H, OCH2CH2O),
6.63 s (2H, Harom), 7.27 s (2H, Harom). Mass spectrum,
m/z (Irel, %): 528 (13) [M]+, 515 (14), 514 (32), 513
(100) [M – Me]+, 250 (30), 249 (30). Found, %:
C 63.86; H 6.83; N 5.36; S 11.89. C28H36N2O4S2.
Calculated, %: C 63.61; H 6.86; N 5.30; S 12.13.
M 528.73.
Ethyl 2-{14,14,15-trimethyl-2,3,5,6,8,9,14,15-
octahydro[1,4,7,10]tetraoxacyclododeca[2,3-g]iso-
quinolin-12(13H)-ylidene}ethanoate (VIIIa) was
purified by column chromatography (chloroform–
acetone, 9:1). Yield 46%, oily substance, Rf 0.3. IR
1
spectrum, ν, cm–1: 1630, 1595, 1512. H NMR spec-
trum, δ, ppm: 1.13–1.31 m (12H, Me), 2.62 q (1H, CH,
J = 7.2 Hz), 3.77 s (4H, O(CH2)2O]; 3.81–3.83 m,
3.87–3.90 m, and 4.21–4.23 m [10H, O(CH2)2O,
OCH2Me]; 4.97 s (1H, CH), 6.73 s (1H, Harom), 7.26 s
(1H, Harom), 8.81 br.s (1H, NH). Found, %: C 65.39;
H 7.47; N 3.26. C22H31NO6. Calculated, %: C 65.17;
H 7.71; N 3.45.
12,14,14,15-Tetramethyl-2,3,5,6,8,9,14,15-octa-
hydro[1,4,7,10]tetraoxacyclododeca[2,3-g]isoquino-
line (VIIIb) was synthesized by heating compound
VIIIa for 2.5 h in boiling 10% H2SO4 and was purified
by column chromatography (EtOAc–EtOH, 1:1).
Yield 74%, oily substance, Rf 0.2. IR spectrum, ν,
1
cm–1: 1624 (C=N), 1600, 1572, 1515. H NMR spec-
trum, δ, ppm: 1.12 d (3H, Me, J = 7.2 Hz); 1.23 s,
1.30 s, and 2.52 s (3H each, Me); 2.68 q (1H, CH, J =
7.2 Hz), 3.77 s [4H, O(CH2)2O]; 3.80–3.83 m, 3.89–
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 3 2014

SHKLYAEV, VSHIVKOVA
380
3.92 m, and 4.18–4.23 m [8H, O(CH2)2O]; 6.78 s (1H,
Harom), 7.22 s (1H, Harom). 13C NMR spectrum, δC,
ppm: 15.7, 18.2, 21.1, 23.0, 26.7, 40.5, 56.6, 57.8,
69.4, 69.7, 70.2, 70.6, 71.3, 73.4, 114.3, 118.4, 138.9,
148.3, 155.2, 164.7. Mass spectrum, m/z (Irel, %): 333
(100) [M]+, 318 (24) [M – Me]+, 291 (7), 230 (10), 202
(13). Found, %: C 68.17; H 8.31; N 4.31. C19H27NO4.
Calculated, %: C 68.44; H 8.16; N 4.20. M 333.42.
68.8, 69.0, 69.4, 76.7, 111.8, 114.0, 121.2, 129.3,
147.5, 151.3, 155.3, 171.1. Mass spectrum, m/z
(Irel, %): 349 (100) [M – CO2Et + H]+, 334 (22) [M –
CO2Et + H – Me]+, 276 (16), 204 (10). Found, %:
C 65.79; H 8.53; N 3.59. C23H35NO6. Calculated, %:
C 65.53; H 8.37; N 3.32.
REFERENCES
14,14,15-Trimethyl-12-(methylsulfanyl)-
2,3,5,6,8,9,14,15-octahydro[1,4,7,10]tetraoxacyclo-
dodeca[2,3-g]isoquinoline (VIIIc) was purified by
column chromatography (hexane–ethyl acetate, 5:1).
Yield 48%, oily substance, Rf 0.2. IR spectrum, ν,
1. Hiraoka, M., Crown Compounds. Their Characteristics
and Applications, Tokyo: Kodansha, 1982.
2. Gragerov, I.P., Kraun-soedineniya v organicheskom
sinteze (Crown Compounds in Organic Synthesis),
Kiev: Naukova Dumka, 1994.
3. Korolev, V.V., Vorobyev, D.Yu., Glebov, E.M., Gri-
vin, V.P., Plyusnin, V.E., Koshkin, A.V., Fedorova, O.A.,
Gromov, S.P., Alfimov, M.V., Shklyaev, Y.V., Vshivko-
va, T.S., Rozhkova, Yu.S., Tolstikov, A.G., Lok-
shin, V.V., and Samat, A., J. Photochem. Photobiol. A:
Chem., 2007, vol. 192, p. 75.
4. Korolev, V.V., Vorobyev, D.Yu., Glebov, E.M., Gri-
vin, V.P., Plyusnin, V.F., Koshkin, A.V., Fedorova, O.A.,
Gromov, S.P., Alfimov, M.V., Shklyaev, Yu.V., Vshivko-
va, T.S., Rozhkova, Yu.S., Tolstikov, A.G., Lok-
shin, V.A., and Samat, A., Mendeleev Commun., 2006,
vol. 16, p. 302.
1
cm–1: 1590, 1555, 1505. H NMR spectrum, δ, ppm:
1.11 d (3H, Me, J = 6.9 Hz), 1.13 s (6H, Me), 2.40 s
(3H, SMe), 2.59 q (1H, CH, J = 6.9 Hz), 3.78 s [4H,
O(CH2)2O]; 3.80–3.83 m, 3.86–3.89 m, and 4.16–
4.23 m [8H, O(CH2)2O]; 6.75 s (1H, Harom), 7.26 s (1H,
Harom). 13C NMR spectrum, δC, ppm: 12.1, 15.5, 24.2,
28.3, 40.6, 58.4, 70.0, 71.2, 71.5, 72.8, 72.9, 115.1,
115.5, 118.6, 121.2, 137.3, 148.3, 153.1, 158.7. Mass
spectrum, m/z (Irel, %): 365 (14) [M]+, 350 (100) [M –
Me]+. Found, %: C 62.67; H 7.62; N 3.67; S 9.01.
C19H27NO4S. Calculated, %: C 62.44; H 7.45; N 3.83;
S 8.77. M 365.49.
5. Chupakhin, O.N., Rusinov, G.L., Beresnev, D.G., and
Itsikson, N.A., Russ. J. Org. Chem., 1999, vol. 35,
p. 1253.
Ethyl 2-[6,7-bis(2-ethoxyethoxy)-3,3-dimethyl-
3,4-dihydroisoquinolin-1(2H)-ylidene]ethanoate
(IX). A mixture of 2.54 g (0.01 mol) of 1,2-bis-
(2-ethoxyethoxy)benzene, 0.72 g (0.01 mol) of iso-
butyraldehyde, and 1.13 g (0.01 mol) of ethyl cyano-
acetate was added dropwise to 5 mL of 96% H2SO4
cooled to 5–10°C. The subsequent procedure was the
same as the general one (see above). The product was
purified by column chromatography (hexane–ethyl
acetate, 5:1). Yield 1.98 g (47%), light yellow oily
substance, Rf 0.2. IR spectrum, ν, cm–1: 1630, 1595,
6. Zhidovinova, M.S., Fedorova, O.V., Rusinov, G.L., and
Ovchinnikova, I.G., Mol. Diversity, 2003, vol. 6, p. 323.
7. Vedernikov, A.I., Ushakov, E.N., Lobova, N.A., Kise-
lev, A.A., Alfimov, M.V., and Gromov, S.P., Izv. Akad.
Nauk, Ser. Khim., 2005, p. 656.
8. Ioffe, S.T. and Nesmeyanov, A.N., Metody elemento-
organicheskoi khimii. Magnii. Berillii. Kal’tsii. Strontsii.
Barii (Methods of Organometallic Chemistry. Magne-
sium, Beryllium, Calcium, Strontium, Barium),
Moscow: Akad. Nauk SSSR, 1963, p. 103.
9. Shklyaev, Yu.V., Gorbunov, A.A., Rozhkova, Yu.S.,
Vshivkova, T.S., Vazhenin, V.V., Maiorova, O.A., Tol-
stikov, A.G., and Dembitsky, V.M., Heteroatom Chem.,
2005, vol. 16, p. 192.
1
1510. H NMR spectrum, δ, ppm: 1.19–1.31 m (9H,
Me), 1.25 s (6H, Me), 2.71 s (2H, CH2); 3.56–3.63 m,
3.77–3.81 m, and 4.12–4.19 m [14H, O(CH2)2OCH2,
OCH2Me]; 5.00 s (1H, CH), 6.65 s (1H, Harom), 7.21 s
(1H, Harom), 8.90 br.s (1H, NH). 13C NMR spectrum,
δC, ppm: 14.7, 15.1, 28.4, 41.6, 49.4, 58.4, 66.7, 66.8,
10. Liu, D.-M., Du, L.-T., Sun, J., and Yan, C.-G., Synth.
Commun., 2010, vol. 40, p. 1333.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 3 2014