Eugenol and its methyl ether in the synthesis of 3-methyl derivatives of 3,4-dihydroisoquinoline

Article abstract of DOI:10.1134/S1070428011020138

3-Methyl derivatives of 1-substituted 3,4-dihydroisoquinoline were obtained proceeding from eugenol and its methyl ether. The propylene oxide in a three-component reaction with veratrol and ethyl cycnoacetate provided the reaction products in a low yield. The isoeugenol in a linear synthesis also gives a low yield of the target compounds.

Full text of DOI:10.1134/S1070428011020138

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 2, pp. 239244. Pleiades Publishing, Ltd., 2011.
Original Russian Text  Yu.V. Shklyaev, A.A. Smolyak, A.A. Gorbunov, 2011, published in Zhurnal Organicheskoi Khimii, 2011, Vol. 47, No. 2, pp. 247252.
Eugenol and Its Methyl Ether in the Synthesis
of 3-Methyl Derivatives of 3,4-Dihydroisoquinoline
Yu. V. Shklyaev,A. A. Smolyak, and A. A. Gorbunov
Institute of Engineering Chemistry, Ural Division, Russian Academy of Sciences
Perm’, 614013 Russia; e-mail: yushka@newmail.ru
Received June 1, 2010
Abstract—3-Methyl derivatives of 1-substituted 3,4-dihydroisoquinoline were obtained proceeding from eugenol
and its methyl ether. The propylene oxide in a three-component reaction with veratrol and ethyl cycnoacetate
provided the reaction products in a low yield. The isoeugenol in a linear synthesis also gives a low yield of the
target compounds.
DOI: 10.1134/S1070428011020138
Quite a number of studies deals with the syntheses
of 3-substituted 3,4-dihydroisoquinoline since the lat-
ter and the easily obtained therefrom 1,2,3,4-tetrahydro
derivatives exhibit a wide range of the biological ac-
tion. 1,3-Dimethyl-3,4-dihydroisoquinoline induces the
Parkinson’s syndrome [1], 7-substituted 1,3-dimethyl-
synthesis of 3,4-dihydroisoquinoline derivatives resulted
only in the preparation of the corresponding 9,10-diethyl-
anthracene [8], whereas the eugenol methyl ether reacted
with veratronitrile in sulfuric acid to give 1-arylsubsti-
tuted 3-methyl-6,7-dimethoxy-3,4-dihydroisoquinoline
[9], but a plausible yield (53%) was obtained only with
1,2,3,4-tetrahydroisoquinolines are inhibitors of the 3,4-dimethoxybenzonitrile whereas with the anisoni-
phenylethanolamine-N-methyltransferase [2], 7-hydroxy- trile the yield of isoquinoline was only 15%, and with
1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid is the 3,4-diethoxybenzonitrile, less than 1%. The reaction of
safrole with 3,4,5-trimethoxybenzonitrile in 48% HBF4
gave the corresponding 3,4-dihydroisoquinoline in 17%
yield whereas in the sulfuric acid only tar was obtained
[10]. Inasmuch as the carbocation character arising in
the protonation of both safrole and eugenol methyl ether
should be the same at the use of the propylene oxide we
used in the first stage of the research two procedures: a,
a three-component synthesis from veratrol, propylene
oxide, and nitriles, and b, from the methyl ether of eu-
genol and nitriles.
inhibitor of NS3 protease of hepatitis C virus [3].
The majority of the preparation methods of 3-methyl
derivatives of 3,4-dihydroisoquinoline is underlain by the
reaction of Bischler–Napieralski. N-(2-Chlorobenzoyl)
amphetamide undergoes the cyclization into 3-methyl-
1-(2-chlorophenyl)-3,4-dihydroisoquinoline at heating in
the presence of POCl3 in 37% yield [4], and 1-phenyl-3,4-
dihydroisoquinoline forms in 13% yield [5]. A series of
1-hetaryl-substituted 3-methyl-3,4-dihydroisoquinolines
was obtained by heating the eugenol methyl ether with
hetarylamides or hetarylaldoximes in POCl3 in 16–35%
yields [6]. (S)-3-Methyl-3,4-dihydroisoquinoline was pre-
pared from the corresponding N-phenethylformamide in
polyphosphoric acid in 65% yield [7]. The application of
Ritter reaction to the preparation of 3-methyl derivatives
of this class compounds would extend the range of reqa-
gents involved and make it possible to obtain compounds
close in the structure to the naturally occurring substances.
The use of the butyric aldehyde in the three-component
The reaction of veratrol, propylene oxide, and ethyl
cycnoacetate brought simultaneously into concn. sul-
furic acid led to the formation in a low yield of ethyl
(2Z)-6,7-dimethoxy-3-methyl-3,4-dihydroisoquinolin-
1(2H)-ylideneacetate (I), and as a side product formed
di(3,4-dimethoxyphenyl)propane. At the use of the eu-
genol methyl ether and ethyl cycnoacetate compound I
was obtained in 22% yield (Scheme 1).
The GC-MS investigation of compound I showed
239

SHKLYAEV et al.
240
out the reaction between the eugenol methyl ether and
acetonitrile that provided compound II whose behavior at
the GC-MS analysis was identical to the above described.
that under the experimental conditions (vaporizer tem-
perature 290°C) ester I suffered a thermolysis [11],
and only the peak of 1,3-dimethyl-6,7-dimethoxy-3,4-
dihydroisoquinoline (II), [M]+• 219 (100) was detected,
the peak of ester I was absent. Analogous pattern was
observed with the (2Z)-(6,7-dimethoxy-3-methyl-3,4-
dihydroisoquinolidene-1-acetamide (III) that similarly
to the previously observed transformation of substituted
amides [12] at the temperature exceeding 100°C dissoci-
ated into compound II and isocyanic acid (Scheme 2).
To confirm this pattern of the reaction course we carried
In a similar way the eugenol methyl ether reacted
with methyl thiocycnate and with 3,4-dimethoxyphenyl-
acetonitrile giving respectively thiolatim ether IV and
ketone VI formed due to the oxidation of compound V
at the isolation [13] (Scheme 3).
As shown in [14] the formation of the 3,4-dihydroiso-
quinoline system under the conditions of Ritter reaction
Scheme 1.
MeO
MeO
MeO
MeO
+
+
NC COOEt
NC COOEt
O
a
MeO
MeO
MeO

NH
N
b
MeO
+
COOEt
I
II
Scheme 2.
MeO
+
+
NC CONH2
NC CONH2
O
MeO
MeO
MeO
MeO
MeO
MeO
MeO

+
HNCO
NH
N
+
CONH2
III
II
Scheme 3.
MeO
MeO
MeO
MeO
H+
+
MeSCN
N
SMe
IV
OMe
MeO
CN
MeO
MeO
H+
[O]
N
N
+
OMe
OMe
MeO
MeO
O
OMe
OMe
OMe
VI
OMe
V
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 2 2011

EUGENOL AND ITS METHYL ETHER
241
was possible even in the presence of a free phenol hy-
EXPERIMENTAL
droxy group in the initial arene. Inasmuch as the use of
the propylene oxide (the synthetic equivalent of the pro-
pionic aldehyde) in the three-component synthesis with
O-methoxyphenol and nitriles leads to the formation of
oligomers, it is clear that in this case only the application
of eugenol or isougenol is possible.
IR spectra were recorded on a spectrophotometer
Bruker from mulls in mineral oil. 1H NMR spectra were
registered on a spectrometer MercuryPlus-300 (300 MHz)
in CDCl3, internal reference HMDS. Mass spectra were
measured on GC-MS instrument Agilent Technologies
6890N/5975B (EI, 70 eV). The monitoring of the reaction
progress and checking the purity of compounds obtained
was performed by TLC on Sorbfil plates, eluent chlo-
roform–acetone, 9:1, development with 0.5% chloranil
solution in toluene. Elemental analysis was carried out
on an analyzer CHNS-932 Leco Corporation.
It is presumable that the reactions of eugenol A and
isoeugenol B would result in different yields for in the
protonated eugenol the carbocation center would arise
in the β-position with respect to arene, whereas in the
isougenol would prevail the α-carbocation much less
reactive in Ritter reaction (Scheme 4) [8, 15].
Actually, in the reactions of eugenol and isoeugenol
with nitriles the yields of products are essentially dif-
ferent. From the eugenol isoquinolines VII–XI were
obtained with a free hydroxy group, but their yield in the
concn. sulfuric acid was relatively small. The reaction in
the methanesulfonic acid improved the yield of the target
products approximately twice (Scheme 5).
Ethyl (2Z)-(6,7-dimethoxy-3-methyl-3,4-dihy-
droisoquinolin-1(2H)-ylidene)acetate (I). a. Amixture
of 1.78 g (0.01 mol) of eugenol methyl ether and 1.13 g
(0.01 mol) of ethyl cyanoacetate was added dropwise
at vigorous stirring to 2 ml of 94% sulfuric acid while
cooling with an ice bath. On completing the addition the
reaction mixture was stirred without cooling for 15 min,
poured into 200 ml of water, and was neutralized with
dry Na2CO3 till pH 8–9. The products were extracted into
50 ml of chloroform. The organic layer was washed with
water (2×50 ml), dried with MgSO4, chloroform was dis-
tilled off on a rotary evaporator. The residue was dissolved
in diethyl ether, and the dry HBr was passed till the forma-
tion of transparent solution. The precipitate was filtered
off and recrystallized from acetonitrile. The hydrobromide
was dissolved in 50 ml of water, neutralized with 10%
aqueous KOH, the separated precipitate was filtered off
The same reactions with isoeugenol resulted mainly
in oligpmers, the isoquinolines were detected only by the
chromatography.
The characteristic feature of compounds VI and XI
is their easy dehydration into the aromatic isoquinolines
in the vaporizer of the GC-MS instrument (290°C):
alongside the dihydroisoquinolines the corresponding
aromatic derivatives always are observed in the ratio ~
1
1:2, although the H NMR spectra prove the exclusive
formation in the synthesis of 3,4-dihydroisoquinolines.
Scheme 4.
+
MeO
HO
MeO
HO
MeO
HO
H+
+
A
B
+
MeO
HO
MeO
HO
MeO
HO
H+
+
+
Scheme 5.
MeO
HO
MeO
HO
H+
+
RCN
N
R
VII_XI
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 2 2011

SHKLYAEV et al.
242
and recrystallized from hexane. Yield 0.63 g (22%), mp
88–90°C. 1H NMR spectrum, δ, ppm: 1.31 d (3H, 3-CH3,
J 12 Hz), 1.29 t (3H, OCH2CH3, J 7.5 Hz), 2.67 m (2H,
C4H2), 3.58 m (1H, H3), 3.87 s (3H, 6-OCH3), 3.88 s (3H,
7-OCH3), 4.16 q (2H, OCH2, J 7.5 Hz), 5.04 c (1H,
Hvinyl), 6.61 s (1H, H5), 7.10 c (1H, H8), 8.88 br.s (1H,
NH). Found, %: C 65.81; H 7.39; N 4.68. C16H21NO4.
Calculated, %: C 65.96; H 7.27; N 4.81.
trile. Yield 1.21 g (46%), yellow crystals, mp 154–156°C,
1
Rf 0.45 (chloroform–acetone, 9:1). H NMR spectrum,
δ, ppm: 1.29 d (3H, 3-CH3, J 6.6 Hz), 2.57 d.d (1H, H4A,
J1 15, J2 11.1 Hz), 2.71 d.d (1H, H4 , J1 15, J2 4.2 Hz),
C
3.54 m (1H, H3), 3.87 s (3H, OCH3), 3.88 s (3H, OCH3),
4.96 s (1H, Hvinyl), 5.10 br.s (2H, NH2), 6.60 s (1H, H5),
7.06 s (1H, H8), 9.47 (1H, NH). Found, %: C 64.25;
H 6.80; N 10.84. C14H18N2O3. Calculated, %: C 64.11;
H 6.92; N 10.68.
b. From a mixture of 1.38 g (0.01 mol) of veratrol,
0.58 g (0.01 mol) propylene oxide, and 1.13 g (0.01 mol)
of ethyl cyanoacetate by procedure a was obtained 0.15 g
(5%) of compound I.
3-Methyl-1-(methylsulfanyl)-6,7-dimethoxy-3,4-
dihydroisoquinoline (IV) was obtained by procedure a
from a mixture of 1.78 г (0.01 mol) of eugenol methyl
ether and 0.73 g (0.01 mol) of methyl thiocyanate. After
distilling off the solvent the residue was crystallized
from hexane. Yield 1.54 g (61%), mp 92–96°C. 1H NMR
spectrum, δ, ppm: 1.33 d (3H, 3-CH3, J 6.6 Hz), 2.42 d.d
1,3-Dimethyl-6,7-dimethoxy-3,4-dihydroisoquin-
oline (II) was obtained by procedure a from a mixture
of 1.78 g (0.01 mol) of eugenol methyl ether and 0.41 g
(0.01 mol) of acetonitrile. After distilling off the solvent
the residue was dissolved in a minimum amount of diethyl
ether, and a saturated solution of salicylic acid in the
same solvent was added. The precipitate formed in 1–2
min was separated and recrystallized from acetonitrile.
The salicylate (mp 149–151°C) was dissolved in 50 ml of
water, neutralized with 10% aqueous KOH, the separated
precipitate was filtered off and recrystallized from hexane.
Yield 0.7 g (32%), mp 74–76°C.
(1H, H4 , J1 18, J2 11.7 Hz), 2.43 s (3H, SCH3), 2.69 d.d
A
(1H, H4 , J1 16, J2 5.1 Hz), 3.66 m (1H, H3), 3.88 s (3H,
C
OCH3), 3.88 s (3H, OCH3), 6.64 s (1H, H5), 7.15 s (1H,
H8). Mass spectrum, m/z (Irel, %): 251 [M]+ (56), 236
[M – Me]+ (100). Found, %: C 62.18; H 6.81; N 5.49;
S 12.88. C13H17NO2S. Calculated, %: C 62.12; H 6.82;
N 5.57; S 12.76.
(3-Methyl-6,7-dimethoxy-3,4-dihydroisoquinolin-
1-yl)(3,4-dimethoxyphenyl)methanone (VI) was
obtained by procedure a from a mixture of 1.78 g
(0.01 mol) of eugenol methyl ether and 1.77 g (0.01 mol)
of 3,4-dimethoxyphenylacetonitrile in 5 ml of dichloro-
methane. After distilling off the solvent the residue was
treated with 2 ml of concn. HCl, and the mixture was
left standing for evaporation over 48 h. The residue was
extracted with 5 ml of boiling acetone, the insoluble
residue was separated and crystallized from ethanol.
Yield 1.54 g (38%) of compound VI hydrochlide, mp
182–184°C. 1 g of the hydrochloride was dissolved
in water, aqueous ammonia was added, the base was
extracted with 50 ml of chloroform, the extract was
dried, the solvent was removed on the rotary evapora-
tor. Yield 0.82 h (90%), Rf 0.6 (hexane–ethyl acetate,
b. Ethyl ester I was dissolved in 35 ml of 10% H2SO4
and the solution was heated for 2 h. Afterwards it was
poured into 200 ml of water, neutralized with dry sodium
carbonate to pH 8–9. The products were extracted into
50 ml of chloroform, the solvent was removed on a rotary
evaporator. The residue was worked up as described in
procedure a. Yield of the salicylate of compound II 1.13 g
(32%), mp 149–151°C. 1H NMR spectrum, δ, ppm: 1.47 d
(3H, 3-CH3, J 7 Hz), 2.88 d.d (1H, H4 , J1 16.8, J2 9.6 Hz),
A
2.98 s (3H, 1-CH3), 3.16 d.d (1H, H4 , J1 16.8, J2 6.3 Hz),
B
3.97 s (3H, OCH3), 4.01 s (3H, OCH3), 4.14 m (1H, H3),
6.71 s (1H, H5), 6.74 d (1H, H5salicyl, J 8 Hz), 6.80 d (1H,
H5salicyl, J 8 Hz), 7.08 C (1H, H8), 7.23 m (1H, H4salicyl),
7.88 d.d (1H, H6salicyl, J1 8, J2 1.5 Hz), 14.95 br.s (1H,
OH). Mass spectrum, m/z (Irel, %): 218 [M]+ (100), 203
[M – Me]+ (80). Hydrochloride, mp 110–112°C. Found,
%: C 61.11; H 6.93; N 5.33. C13H17NO2·HCl. Calculated,
%: C 61.05; H 7.09; N 5.48.
1
5 : 1), mp 115–117°C (hexane). H NMR spectrum, δ,
ppm: 1.44 d (3H, 3-CH3, J 7.1 Hz), 2.61 d.d (1H, H4A,
J1 15.6, J2 11.4 Hz), 2.86 d.d (1H, H4 , J1 15.9, J2 5.4 Hz),
C
3.76 s (3H, 6-OCH3), 3.85 m (1H, H3), 3.91 s (3H,
7-OCH3), 3.92 C (3H, 4’-OCH3), 3.93 C (3H, 3’-OCH3),
6.73 s (1H, H5), 6.87 d (1H, H5, J 3 Hz), 6.88 s (1H, H8),
7.60 d.d (1H, H6, J1 8.25, J2 1.8 Hz), 7.67 d (1H, H2’,
J 1.8 Hz). Mass spectrum, m/z (Irel, %): 369 [M]+ (20),
354 [M – Me]+ (8), 165 [3,4-dimethoxyphenylcarbonyl]+
(2Z)-(6,7-Dimethoxy-3-methyl-3,4-dihydroiso-
quinolin-1(2H)-ylidene)ethanamide (III) was obtained
by procedure a from a solution of 0.84 g (0.01 mol) of
cyanacetamide in 2 ml of cold 94% sulfuric acid and
1.78 g (0.01 mol) of eugenol methyl ether.After distilling
off the solvent the residue was crystallized from acetoni-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 2 2011

EUGENOL AND ITS METHYL ETHER
243
(80). Found, %: C 68.12; H 6.39; N 3.73. C21H23NO5.
Calculated, %: C 68.28; H 6.28; N 3.79.
solvent the residue was dissolved in diethyl ether, and the
dry HCl was passed, the precipitate was separated and
recrystallized first from acetone and then from acetoni-
trile. Yield 1.8 g (66%), light-brown needle crystals, mp
193–195°C, Rf 0.7 (chloroform–acetone, 9 : 1). 1H NMR
spectrum, δ, ppm: 1.36 d (3H, 3-CH3, J 6.6 Hz), 2.76 d.d
Ethyl (2Z)-(7-hydroxy-6-methoxy-3-methyl-3,4-
dihydroisoquinolin-1(2H)-ylidene)ethanoate (hydro-
chloride) (VII). Amixture of 1.64 g (0.01 mol) of eugenol
and 1.13 g (0.01 mol) of ethyl cyanoacetate was added
dropwise at vigorous stirring and cooling with ice to 5 ml
of methanesulfonic acid. On completion of the addition
the reaction mixture was stirred without cooling for 15
min, then it was poured into 200 ml of water and neutral-
ized with dry sodium carbonate to pH 8–9. The products
were extracted into 50 ml of chloroform. The organic
layer was washed with water (2×50 ml), dried, chloroform
was distilled off on a rotary evaporator. The residue was
dissolved in diethyl ether, and the dry HCl was passed
till the formation of transparent solution. The precipitate
was filtered off, dried, and crystallized from acetoni-
trile. Yield 1.08 g (34%), mp 166–168°C, Rf 0.7 (ethyl
acetate–hexane, 2:1). 1H NMR spectrum, δ, ppm: 1.21 t
(3H, OCH2CH3, J 7.2 Hz), 1.57 d (3H, 3-CH3, J 6.6 Hz),
2.87 d.d (1H, H4 , J1 15.5, J2 9.9 Hz), 3.15 d.d (1H, H4 ,
(1H, H4 , J1 16.8, J2 2.4 Hz), 3.06 s (3H, SMe), 3.27 d.d
A
(1H, H4 , J1 16.7, J2 3.3 Hz), 4.00 s (3H, OMe), 4.60 m
C
(1H, H3), 6.76 s (1H, OH), 7.26 d (1H, H5, J 4.8 Hz),
7.64 d (1H, H8, J 4.8 Hz), 12.89 C (1H, HCl). Mass
spectrum, m/z (Irel, %): 237 [M]+• (63), 236 [M – H]+ (80),
221 [M – Me]+ (100). Found, %: C 52.54; H 5.99; N 5.31;
S 11.57. C12H15NO2S·HCl. Calculated, %: C 52.65;
H 5.89; N 5.12; S 11.71.
(2Z)-(7-Hydroxy-3-methyl-6-methoxy-3,4-dihy-
droisoquinolin-1(2H)-ylidene)ethanamide (X). To
a solution of 0.01 mol of cyanacetamide in 2 ml of 94%
sulfuric acid at vigorous stirring and cooling with ice was
added dropwise 0.01 mol of eugenol. Further workup was
performed as in the preparation of compound I. After
removing the solvent the residue was crystallized from
ethanol. Yield 1.21 g (46%), yellow crystals, mp 197–
199°C. 1H NMR spectrum, δ, ppm: 1.27 d (3H, 3-CH3,
J 6.3 Hz), 2.62 m (1H, H4 ), 2.71 m (1H, H4 ), 3.51 m
A
C
J1 8.3, J2 6.3 Hz), 4.00 s (3H, OMe), 4.15 m (1H, H3),
4.42 q (2H, OCH2, J 7.2 Hz), 6.82 s (2H, C1H2), 7.29 d
(1H, H5, J 2.1 Hz), 7.43 d (1H, H8, J 3.9 Hz), 7.87 br.s
(1H, NH), 14.15 br.s (1H, OH). Found, %: C 57.50;
H 6.39; N 4.47. C15H19NO4·HCl. Calculated, %: C 57.42;
H 6.42; N 4.46.
A
C
(1H, H3), 3.87 s (3H, OCH3), 4.99 C (1H, Hvinyl), 5.61
br.s (2H, NH2), 6.62 s (1H, H5), 7.13 s (1H, H8), 8.48 s
(1H, OH), 9.39 s (1H, NH). Mass spectrum, m/z (Irel,
%): 237 [M]+• (63), 236 [M – H]+ (80), 221 [M – Me]+
(100). Found, %: C 54.66; H 6.14; N 9.72. C13H16N2O3.
Calculated, %: C 54.84; H 6.02; N 9.84.
Compounds VIII and IX were similarly obtained.
7-Hydroxy-1,3-dimethyl-6-methoxy-3,4-dihy-
droisoquinoline (hydrochloride) (VIII) was obtained
from the mixture of 0.02 mol of eugenol and 0.02 mol of
acetonitrile. After removing the solvent the residue was
dissolved in diethyl ether, and the dry HCl was passed,
the precipitate was separated and recrystallized first from
acetone and then from ethanol. Light-brown crystals.
Yield 1.30 g (26%), mp 119–121°C. 1H NMR spectrum,
δ, ppm: 1.41 d (3H, 3-CH3, J 6.6 Hz), 2.73 s (3H, 1-CH3),
2.82 d.d (1H, 4H, J1 16.5, J2 10.8 Hz), 3.09 d.d (1H, 4H,
J1 16.5, J2 6.3 Hz), 3.92 s (3H, OMe), 4.06 m (1H, H3),
7.05 s (1H, H5), 7.42 d (1H, H8, J 0.6 Hz), 9.84 s (1H,
OH), 13.34 br.s (1H, NH). Mass spectrum, m/z (Irel, %):
205 [M]+• (100), 190 [M – Me]+ (100). Found, %: C 59.49;
H 6.54; N 5.89. C12H15NO2·HCl. Calculated, %: C 59.63;
H 6.67; N 5.79.
(7-Hydroxy-3-methyl-6-methoxy-3,4-dihydroiso-
quinolin-1-yl)(3,4-dimethoxyphenyl)methanone
(hydrochloride) (XI) was obtained like compound VII
from the mixture of 0.01 mol of eugenol and 0.01 mol
of 3,4-dimethoxyphenylacetonitrile in 5 ml of dichloro-
methane. After distilling off the solvent the residue was
treated with 2 ml of concn. HCl, and the mixture was left
standing for evaporation over 48 h. The residue was ex-
tracted with 5 ml of boiling acetone, the insoluble residue
was filtered off, dried, and crystallized from acetonitrile.
Yield 1.20 g (31%), light-yellow crystals, mp 209–210°C.
1H NMR spectrum, δ, ppm: 1.41 d (3H, 3-CH3, J 5.7 Hz),
2.58 m (1H, H4 ), 2.82 d.d (1H, H4 , J1 16, J2 4.8 Hz),
A
C
3.83 m (1H, H3), 3.90 m (12H, OMe), 5.80 br.s (1H, OH),
6.67 s (1H, H5), 6.81 d (1H, H5, J 5 Hz), 6.83 s (1H, H8),
7.52 d (1H, H2’, J 8.4 Hz), 7.63 s (1H, H6’). Mass spec-
trum, m/z (Irel, %): 355 [M]+ (24), 340 [M – Me]+ (9), 336
[M – OH]+ (100), 165 [eugenol + H]+ (100). Found, %:
7-Hydroxy-3-methyl-1-(methylsulfanyl)-6-me-
thoxy-3,4-dihydroisoquinoline (hydrochloride) (IX)
was obtained from the mixture of 0.01 mol of eugenol
and 0.01 mol of methyl thiocyanate. After removing the
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 2 2011

SHKLYAEV et al.
244
p. 5058.
C 61.19; H 5.73; N 3.39. C20H21NO5·HCl. Calculated,
%: C 61.30; H 5.66; N 3.57.
6. Kametani, T., Otsuki, K., and Fukui, M., Pharm. Soc. Jpn.,
1955, vol. 3, p. 266.
ACKNOWLEDGMENTS
7. Fecik, R.A., Devasthale, P., Pillai, S., Keschavarz-Shokri,
A., Shen, L., and Mitscher, L.A., J. Med. Chem., 2005, vol.
48, p. 1229.
The study was carried out under the financial support
of the program of the Presidium of the RussianAcademy
of Sciences no. 18.
8. Shklyaev, Yu.V. and Nifontov, Yu.V., Izv. Akad. Nauk, Ser.
Khim., 2002, p. 780.
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