Rearrangements of N-ethoxycarbonylmethyl-1,2,3,4-tetrahydroquinolinium halogenalkylates effected by sodium hydride. Synthesis of 2,3,4,5-tetrahydro-1H- 3-benzazepines

Article abstract of DOI:10.1134/S1070428008050205

Quaternary salts obtained from N-alkyl-1,2,3,4-tetrahydroisoquinolines and ethyl haloacetates or diethyl bromomalonate under the action of sodium hydride in boiling 1,4-dioxane were converted into N-alkyl-N-ethoxycarbonyl-2,3,4,5- tetrahydro-1H-3-benzazep

Full text of DOI:10.1134/S1070428008050205

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2008, Vol. 44, No. 5, pp. 750−754. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © G.S. Gimranova, S.A. Soldatova, A.T. Soldatenkov, K.B. Polyanskii, 2008, published in Zhurnal Organicheskoi Khimii, 2008,
Vol. 44, No. 5, pp. 758−762.
Rearrangements
of N-Ethoxycarbonylmethyl-1,2,3,4-tetrahydroquinolinium
Halogenalkylates Effected by Sodium Hydride.
Synthesis of 2,3,4,5-Tetrahydro-1H-3-benzazepines
G. S. Gimranova, S. A. Soldatova, A. T. Soldatenkov, and K. B. Polyanskii
Russian University of Peoples’ Friendship, Moscow, 117198 Russia
e-mail: guzelia2@yandex.ru
Received July 17, 2007
Abstract—Quaternary salts obtained from N-alkyl-1,2,3,4-tetrahydroisoquinolines and ethyl haloacetates or diethyl
bromomalonate under the action of sodium hydride in boiling 1,4-dioxane were converted into N-alkyl-N-
ethoxycarbonyl-2,3,4,5-tetrahydro-1H-3-benzazepines in 49–60% yield. From the reaction mixture by column
chromatography products of β-elimination by Hofmann reaction, 2-(N-methyl-N-ethoxycarbonylmethyl)-
aminomethylstyrenes were also isolated (yield 0.6–16%).
DOI: 10.1134/S1070428008050205
We reported in [1] on rearrangements of N-ylides
generated from 1-methyl-4-aryl-1-ethoxycarbonylmethyl-
1,2,3,6-tetrahydropyridinium halides. It was established
that these anhydrobases at boiling in aprotic solvents
underwent recyclization forming 3-aryl-3-vinyl-1-methyl-
2-ethoxycarbonylpyrrolidones and/or 2-alkoxycarbonyl-
1-methyl-5-aryl-2,3,6,7-tetrahydro-1H-azepines. Both at
the contraction of initial heterocycle (as a result of [2,3]-
sigmatropic rearrangement) and its expansion (due to
[1,2]-shift by Stevens rearrangement) the reaction center
was the allylamine fragment in the N-ylide. Inasmuch as
the quaternary salts of C-unsubstituted tetrahydro-
pyridines suffered only the [2,3]-sigmatropic rear-
rangement [2] and the introduction of an aryl substituent
to C4 position provided a possibility of the [1,2]-shift
[1], we decided to investigate the direction of molecular
rearrangements in quaternary salts of 1,2,3,4-tetra-
hydroisoquinolinium.
an intermediate quinone methide arising by the cleavage
of the allylamine fragment at the C–N bond. In [4] it
was stated that an analogous salt, N-[(trimethylsilyl)-
methyl]tetrahydroisoquinolinium iodomethylate, could
in the absence of bases (under the action of cesium
fluoride) convert into a tetrahydroazepine system when
in the position 1 of the initial salt a phenyl substituent
was present.
In the present study we performed quaternization of
N-methyl- or N-ethyl-1,2,3,4-tetrahydroisoquinolines
with α-halo derivatives of ethyl acetate at room
temperature in ethyl acetate to obtain in high yields (85–
98%) quaternary salts Ia, Ib and Va, Vb. At the use of
the 2-bromomalonic acid ester the yield of salt IX was
considerably lower (to 60%). Further reaction of salts I,
V, and IX with sodium hydride in the boiling 1,4-dioxane
under argon atmosphere led to the formation of
tetrahydrobenzazepines II, VI, and X and of amino-
methylstyrenes IV and VIII. The products were isolated
by chromatography with the yields 49–60 and 0.6–16%
respectively (Scheme 1).
Only two papers were published on this subject [3,
4]. In [3] it was reported that N-(4-nitrobenzyl)-6-
hydroxy-1,2,3,4-tetrahydroisoquinolinium bromomethyl-
ate under the action of potassium tert-butylate in butanol
rearranged into tetrahydrobenzazepine, and its 6-methoxy
analog suffered Hofmann elimination. On this grounds
it was concluded that the benzazepine did not form by
Stevens rearrangement but the reaction proceeded through
In the mass spectra (LCMS) also the formation was
detected of intermediate N-ylides III and VII that
subsequently transformed into the rearrangement
products II and VI and in the products of Hofmann
elimination IV and VIII. In going to 6,7-dimethoxy-
750

REARRANGEMENTS OF N-ETHOXYCARBONYLMETHYL-1,2,3,4-TETRAHYDROQUINOLINIUM
751
2
substituted isoquinolinium bromides Va and Vb the yield
of the products of Hofmann elimination sharply
decreased. The substitution for two deuterium atoms of
two protons attached to C4 did not affect the yields of
with the geminal coupling constant J 1.2 Hz, and the
methine proton of the =NCH(D)C=O group gave rise to
a narrow singlet (1H) at 3.71 ppm (a similar methine
proton in the spectrum of benzazepine VIb was observed
in the region 3.53 ppm as a one-proton doublet of
doublets). In the mass spectrum (LCMS) of the elimina-
tion product VIIIb a peak of molecular ion [M + 1]+ of
mass 296 appeared indicating that its structure contained
two deuterium atoms. These data suggest that the elimina-
tion occurred here through an intramolecular transfer of
one axial deuterium atom.
1
the rearranged products VIb and VIIIb. H NMR and
mass spectra of partially deuterated compounds VIb and
VIIIb indicate that in benzazepine VIb, the product of
[1,2]-shift by Stevens mechanism, both deuterium atoms
remained in the previous position at (Scheme 2).
At the same time in the course of formation of the
product of Hofmann elimination VIIIb one deuterium
atom relocated to C-ylide atom (Scheme 3). This is
confirmed by 1H NMR spectrum where two protons Ha
and Hb of the vinyl group Ar(D)C=CHa2,b appeared at
5.15 and 5.65 ppm as two narrow doublets (1H each)
We established by the study of the behavior of the
quaternary salt IX obtained by quaternization with
bromomalonic ester that the existence of steric
hindrances to the Stevens rearrangement did not hamper
Scheme 1.
Hc
Hb
NaH
Ha
R
N
R
N+
Cl_
N+
_ R
N
R
CH2COOEt
CH2COOEt
HC
COOEt
COOEt
IIa, IIb
IVa, IVb
Ia, Ib
IIIa, IIIb
R = Me (a), Et (b).
Scheme 2.
R
R
R
R
Br_
MeO
MeO
MeO
NaH
N Me
COOEt
N+ Me
MeO
CH2COOEt
VIa, VIb
Va, Vb
Hb
R
R
R
MeO
MeO
MeO
Ha
N
N+
_ Me
HC
CHCOOEt
MeO
Me
R
COOEt
VIIa, VIIb
VIIIa, VIIIb
R = H (a), D (b).
Scheme 3.
Et
Et
O
O
D
C_
N+
O
O
D
NaH
Vb
VIIIb
N+
OMe
OMe
OMe
OMe
C_
Me
Me
D
D
VIIb
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 5 2008

GIMRANOVA et al.
752
Scheme 4.
Br _
deutero-N-methyl-6,7-dimethoxy-1,2,3,4-tetrahydroiso-
quinoline were obtained from the corresponding 3,4-
dimethoxyphenylacetonitriles as described in [5].
N+
Quaternary salts Ia, Ib, Va, Vb, and IX. General
procedure. A solution of 100 mmol of N-alkyl-1,2,3,4-
tetrahydroisoquinoline and 120 mmol of an ester of
haloacetic or bromomalonic acid in 50 ml of anhydrous
ethyl acetate was maintained for 5–12 h at 20°C. The
reaction mixture was filtered, the isolated precipitate was
washed with ethyl acetate. The reaction product was
obtained in the form of colorless crystals.
Et
COOEt
EtOOC
IX
NaH
N Et
COOEt
N
Et
2-Methyl-2-(2-ethoxy-2-oxoethyl)-1,2,3,4-tetra-
hydroisoquinolinium chloride (Ia). Yield 2.42 g (90%),
mp 165–167°C. IR spectrum, ν, cm–1: 1748 (C=O).
1H NMR spectrum, δ, ppm: 1.23 t (3H, CH2CH3,
J 7.3 Hz), 3.36 s (3H, NCH3), 3.44 s (2H, NCH2CO),
EtOOC
the formation of the tetrahydrobenzazepine ring
(Scheme 4). In this case tetrahydrobenzazepine X was
isolated in 60% yield.
3
3.99 m (2H, H4), 4.22 q (2H, CH2CH3, J 7.3 Hz),
At the same time the expected β-elimination side
product of the type IV or VIII was not detected even by
the LCMS method apparently because of the easy
cleavage of the large substituent at nitrogen resulting in
the fast formation of the initial base, 2-ethyltetra-
hydroisoquinoline, isolated in 30% yield.
4.65 m (2H, H3), 4.80 d, 4.87 d (1H each, H1,
2J 15.0 Hz), 7.05–7.55 m (4Harom). Found, %: C 62.30;
H 7.45; Cl 13.10; N 5.16. C14H20ClNO2. Calculated, %:
C 62.33; H 7.47; Cl 13.14; N 5.19.
2-Ethyl-2-(2-ethoxy-2-oxoethyl)-1,2,3,4-tetra-
hydroisoquinolinium chloride (Ib). Yield 2.46 g (87%),
mp 178–180°C. IR spectrum, ν, cm–1: 1740 (C=O).
1H NMR spectrum, δ, ppm: 1.15 t (3H, NCH2CH3,
3J 7.1 Hz), 1.25 t (3H, OCH2CH3, 3J 7.0 Hz), 3.40 s (2H,
NCH2CO), 3.86–4.20 m (4H, H4, NCH2CH3), 4.22 q (2H,
OCH2CH3, 3J 7.00 Hz), 4.49 m (2H, H3), 4.90 d, 4.95 d
(ïO 1H, H1, 2J 15.0 Hz), 7.07–7.44 m (4Harom). Found,
%: C 63.35; H 7.89; Cl 12.45; N 4.93. C15H22ClNO2.
Calculated, %: C 63.48; H 7.81; Cl 12.49; N 4.94.
EXPERIMENTAL
IR spectra were recorded on a spectrophotometer
Specord 75IR from pellets with KBr or mulls in mineral
oil. H NMR spectra were registered on spectrometers
1
Varian DPX-300 (operating frequency 300 MHz) and
Bruker WM-400 (operating frequency 400 MHz) from
solutions in DMSO-d6 (compounds Ia, Ib, Va, Vb, and
IX) and in CDCl3 (compounds IIa, IIb, IVa, IVb, VIa,
VIb, VIIIa, VIIIb, and X). the designation of vinyl group
protons in styrenes IVa, IVb and VIIIa, VIIIb are given
on the schemes of reactions of their syntheses. Electron-
impact mass spectra were obtained on a chromato-mass-
spectrometer Finnigan MAT 95XL, ionizing electrons
energy 70 eV. Mass spectra in the LCMS mode (ioniza-
tion with H+) were taken on a chromato-mass-spectrom-
eter PE SCIEX API 165(150) (Shimadzu HPLC
SCL10Avp, autosampler Gilson 215, ELSD Sedex 75).
The preparative column chromatography was performed
on silica gel L60 (40/100). The reaction progress was
monitored and the purity of compounds synthesized was
checked by TLC on Silufol UV-254 plates. Initial
N-methyl- and N-ethyl-1,2,3,4-tetrahydroisoquinolines
were preaped by N-alkylation of commercial 1,2,3,4-
tetrahydroisoquinoline (Aldrich). N-methyl-6,7-di-
methoxy-1,2,3,4-tetrahydroisoquinoline and 4,4-di-
2-Methyl-6,7-dimethoxy-2-(2-ethoxy-2-oxoethyl)-
1,2,3,4-tetrahydroisoquinolinium bromide (Va). Yield
3.67 g (98%), mp 163–165°C. IR spectrum, ν, cm–1: 1738
1
(C=O). H NMR spectrum, δ, ppm: 1.25 t (3H,
3
OCH2CH3, J 7.0Hz ), 3.10 br.s (2H, H4), 3.29 s (3H,
NCH3), 3.73 s, 3.76 s (3H each, OCH3), 3.88 m (2H,
3
H3), 4.25 q (2H, OCH2CH3, J 7.0 Hz), 4.53 d, 4.57 d
2
(1H each, H1, J 16.4 Hz), 4.70 d, 4.78 d (ïO 1H,
2
NCH2CO, J 16.8 Hz), 6.80 C, 6.90 C (ïO 1H, H5,8).
Found, %: C 51.19; H 6.50; Br 21.29; N 3.75.
C16H24BrNO4. Calculated, %: C 51.35; H 6.46; Br 21.35;
N 3.74.
4,4-Dideutero-2-methyl-6,7-dimethoxy-2-(2-
ethoxy-2-oxoethyl)-1,2,3,4-tetrahydroisoquinolinium
bromide (Vb). Yield 3.2 g (85%), mp 162–164°C. IR
spectrum, ν, cm–1: 1738 (C=O). 1H NMR spectrum, δ,
3
ppm: 1.25 t (3H, OCH2CH3, J 7.0 Hz), 3.29 s (3H,
NCH3), 3.73 s, 3.76 s (3H each, OCH3), 3.86 d, 3.92 d
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 5 2008

REARRANGEMENTS OF N-ETHOXYCARBONYLMETHYL-1,2,3,4-TETRAHYDROQUINOLINIUM
753
trum, m/z (Irel, %): 233 (3) [M]+, 160 (100), 158 (3), 145
(7), 117 (9), 91 (4).
2
(1H each, H3, J 12.1 Hz), 4.25 q (2H, OCH2CH3,
3J 7.0 Hz), 4.53 d, 4.57 d (1H each, H1, J 16.4 Hz),
2
4.70 d, 4.78 d (1H each, NCH2CO, 2J 16.8 Hz), 6.80 s,
6.90 s (1H each, H5,8). Found, %: Br 21.25; N 3.71.
C16H22BrD2NO4. Calculated, %: Br 21.23; N 3.72.
Ethyl N-(2-vinylbenzyl)-N-methylglycinate (IVa).
Yield 0.03 g (16%), thick oily substance. IR spectrum,
ν, cm–1: 1740 (C=O). 1H NMR spectrum, δ, ppm: 1.30 t
3
(3H, OCH2CH3, J 7.1 Hz), 2.40 s (3H, NCH3), 3.30 s
2-Ethyl-2-[di(ethoxycarbonyl)methyl]-1,2,3,4-
tetrahydroisoquinolinium bromide (IX). Yield 2.6 g
(65%), mp 177–179°C. IR spectrum, ν, cm–1: 1743 br
(2H, NCH2Ar), 3.75 m (2H, NCH2CO), 4.20 q
3
2
(2H, OCH2CH3, J 7.1 Hz), 5.32 d.d (1H, Hb, J 1.0,
3J 11.0 Hz), 5.68 d.d (1H, Ha, J 1.0, J 15.0 Hz),
7.20–7.70 m (4H, HC and Harom), 7.56 d.d (1Harom
2
3
1
(C=O). H NMR spectrum, δ, ppm: 1.30 t (6H,
OCH2CH3, 3J 7.2 Hz), 1.51 t (3H, NCH2CH3, 3J 7.1 Hz),
3.25 m (2H, H4), 3.84 m (4H, H3 and NCH2CH3), 4.38 m
(4H, OCH2CH3), 4.90 d, 4.94 d (1H each, H1,
2J 16.8 Hz), 6.07 s (1H, CHCOO), 7.08–7.27 m (4Harom).
Found, %: C 54.0; H 6.52; Br 19.94; N 3.2.
C18H26BrNO4. Calculated, %: C 54.01; H 6.55; Br 19.96;
N 3.5.
,
J 7.6 1.1 Hz). Mass spectrum, m/z (Irel, %): 233(19) [M]+,
218 (2), 204 (3), 160 (74), 146 (4), 117 (100), 116 (10),
115 (25), 91 (9). Found, %: C 72.04; H 8.19; N 5.96.
C14H19NO2. Calculated, %: C 72.07; H 8.21; N 6.0.
3-Ethyl-2-ethoxycarbonyl-2,3,4,5-tetrahydro-1H-
3-benzazepine (IIb). Yield 0.13 g (55%), thick oily
substance. IR spectrum, ν, cm–1: 1730 (C=O). 1H NMR
Benzazepines IIa, IIb, VIa, VIb, and X and amino-
methylstyrenes IVa, IVb and VIIIa, VIIIb. General
procedure. To a dispersion of 1 mmol of tetrahydroiso-
quinolinium quaternary salts Ia, Ib, Va, Vb, and IX in
30 ml of anhydrous dioxane was added at 20°C 0.28 g
(1.2 mmol) of sodium hydride under an argon atmosphere.
The mixture was boiled for 7 h, then the reaction mixture
was cooled, excess NaH was decomposed by ethanol,
and the solvents were removed in a vacuum. The residue
was treated with water, the organic compounds were
extracted into CH2Cl2. The extract was twice washed
with water, dried by anhydrous MgSO4, and the solvent
was evaporated in a vacuum. The oily residue was
subjected to column chromatography on silica gel. At
elution with hexane–ethyl acetate, 10:1, were isolated
aminomethylstyrenes IVa, IVb and VIIIa, VIIIb; at
elution with hexane–ethyl acetate, 2:1, were isolated
benzazepines IIa, IIb, VIa, VIb, and X.
3
spectrum, δ, ppm: 1.19 t (3H, NCH2CH3, J 7.00 Hz),
1.24 t (3H, OCH2CH3, 3J 7.2 Hz), 2.66–2.98 m (4H, H1
and H5), 3.11 t (1H, H4, J 13.5 Hz), 3.22–3.37 m (4H, H4
and NCH2CH3), 3.81 d.d (1H, H2, J 6.8, 7.2 Hz), 4.04 q
(2H, OCH2CH3, 3J 7.2 Hz), 7.03–7.26 m (4Harom). Mass
spectrum, m/z (Irel, %): 247 (3) [M]+, 174 (100), 145 (7),
117 (8), 115 (6). Found, %: C 72.79; H 8.54; N 5.62.
C15H21NO2. Calculated, %: C 72.84; H 8.56; N 5.66.
2-Ethyl-1,2,3,4-tetrahydroisoquinolinium 2-ethoxy-
carbonylmethylide (IIIb). Characterized by chromato-
mass-spectrometry. Yield 14%. Mass spectrum, m/z (Irel,
%): 247 (2) [M]+, 218 (5), 160 (100), 158 (4), 130 (4).
Ethyl N-(2-vinylbenzyl)-N-ethylglycinate (IVb).
Yield 0.03 g (14%), yellowish thick oily substance. IR
spectrum, ν, cm–1: 1740 (C=O). 1H NMR spectrum, δ,
ppm: 1.18 t (3H, NCH2CH3, 3J 7.1 Hz), 1.24 t (3H,
OCH2CH3, 3J 7.2 Hz), 3.30 s (3H,ArCH2N), 3.38 q (2H,
3
3-Methyl-2-ethoxycarbonyl-2,3,4,5-tetrahydro-
1H-3-benzazepine (IIa). Yield 0.11 g (49%), colorless
thick oily substance. IR spectrum, ν, cm–1: 1730 (C=O).
1H NMR spectrum, δ, ppm: 1.40 t (3H, CH2CH3, J 7.2 Hz),
2.50 s (3H, NCH3), 2.67 m (1H, H4), 2.91–3.05 m (2H,
H1), 3.17 m (2H, H5), 3.26 t (1H, H4, J 14.1 Hz),
3.47 d.d (1H, H2, J 7.0, 3.4 Hz), 4.08 q (2H, CH2CH3,
J 7.2 Hz), 7.05–7.18 m (4H, HC and Harom). Mass
spectrum, m/z (Irel, %): 233 [M]+ (3), 218 (4), 146 (100),
144 (100), 144 (7), 131 (5), 115 (4), 94 (3). Found, %:
C 72.00; H 8.18; N 6.0. C14H19NO2. Calculated, %:
C 72.07; H 8.21; N 6.0.
NCH2CH3, J 7.1 Hz), 3.60 s (2H, NCH2CO), 4.06 q
3
2
(2H, OCH2CH3, J 7.2 Hz), 5.28 d.d (1H, Hb, J 1.0,
3J 10.9 Hz), 5.72 d.d (1H, Ha, 2J 1.0, 3J 14.8 Hz), 7.15–
7.30 m (4H, HC and Harom), 7.58 d (1Harom, J 7.2 Hz).
Mass spectrum, m/z (Irel, %): 247 (35) [M]+, 218 (5),
174 (100), 117 (95), 115 (28), 91 (10). Found, %: C 72.80;
H 8.53; N 5.64. C15H21NO2. Calculated, %: C 72.84;
H 8.56; N 5.66.
3-Methyl-7,8-dimethoxy-2-ethoxycarbonyl-
2,3,4,5-tetrahydro-1H-3-benzazepine (VIa). Yield
0.16 g (56%), yellow thick oily substance. IR spectrum,
ν, cm–1: 1727 (C=O). 1H NMR spectrum, δ, ppm: 1.16 t
3
2-Methyl-1,2,3,4-tetrahydroisoquinolinium 2-
ethoxycarbonylmethylide (IIIa). Characterized by
chromato-mass-spectrometry. Yield 13%. Mass spec-
(3H, OCH2CH3, J 7.1 Hz), 2.40 s (3H, NCH3), 3.10–
3.16 m (4H, H1 and H5), 3.24 m (2H, H4), 3.51 d.d (1H,
H2, J 6.9 and 3.2 Hz), 3.70 s (3H, OCH3), 3.75 m (3H,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 5 2008

GIMRANOVA et al.
754
OCH3), 3.90 q (2H, OCH2CH3, 3J 7.1 Hz), 6.48 s, 6.62 s
(1H each, H6 and H9). Mass spectrum, m/z: 294 [M +
1]+. Found, %: C 65.49; H 7.87; N 4.75. C16H23NO4.
Calculated, %: C 65.51; H 7.90; N 4.77.
3.82 s (3H, CH3O), 4.01 q (2H, OCH2CH3, 3J 7.2 Hz),
5.15 d (1H, Hb, 2J 1.2 Hz), 5.65 d (1H, Ha, 2J 1.2 Hz),
6.90 s, 7.10 s (1H each, H3,6). Mass spectrum: m/z 296
[M + 1]+. Found, %: N 4.72. C16H21D2NO4. Calculated,
%: N 4.74.
2-Methyl-6,7-dimethoxy-1,2,3,4-tetrahydro-
isoquinolinium 2-ethoxycarbonylmethylide (VIIa).
Characterized by chromato-mass-spectrometry. Yield
12%. Mass spectrum, m/z (Irel, %): 294 [M + 1]+.
3-Ethyl-2,2-di(ethoxycarbonyl)-2,3,4,5-tetra-
hydro-1H-benzazepine (X). Yield 0.19 g (60%), thick
oily substance. IR spectrum, ν, cm–1: 1737 (C=O).
1H NMR spectrum, δ, ppm: 1.16 t (3H, NCH2CH3,
3J 7.21 Hz), 1.23 t (6H, OCH2CH3, 3J 7.1 Hz), 2.87 m
(2H, H5, 3J 5.7 Hz), 3.03 t (2H, H5, J 5.7 Hz), 3.93 s (2H,
H1), 4.25 m (6H, CH2CH3), 6.93 d.d (1H, H9, J 7.0 and
3.4 Hz), 7.03 m (3Harom). Mass spectrum: m/z 320 [M +
1]+. Found, %: C 67.67; H 7.85; N 4.37. C18H25NO4.
Calculated, %: C 67.69; H 7.89; N 4.39. From the reaction
mixture by chromatography was also isolated 2-ethyl-
1,2,3,4-tetrahydroisoquinoline (initial base for the
synthesis of quaternary salt IX). Thick oily substance.
Yield 0.04 g (30%). 1H NMR and mass spectra identical
to those of the initial 2-ethyltetrahydroisoquinoline.
Ethyl N-(2-vinyl-4,5-dimethoxybenzyl)-N-methyl-
glycinate (VIIIa). Yield 0.007 g (0.6%), thick oily
substance. IR spectrum, ν, cm–1: 1737 (C=O). 1H NMR
spectrum (CDCl3), δ, ppm: 1.30 t (3H, CH2CH3,
3J 7.2 Hz), 2.42 s (3H, NCH3), 3.25 s (2H, NCH2Ar),
3.70 s (2H, NCH2CO), 3.90 s, 3.94 s (3H each, OCH3),
4.21 q (2H, OCH2, 3J 7.2 Hz), 5.23 d.d (1H, Hb, 2J 1.2,
3J 11.0 Hz), 5.58 d.d (1H, Ha, J 1.2 and 15.0 Hz),
6.9 d.d, 7.06 d.d (1H each, H3,6, 5J 0.8 Hz), 7.17 q (1H,
HC, J 15.0 and 11.0 Hz). Mass spectrum, m/z: 294 [M +
1]+. Found, %: C 65.49; H 7.89; N 4.75. C16H23NO4.
Calculated, %: C 65.51; H 7.90; N 4.77.
5,5-Dideutero-3-methyl-7,8-dimethoxy-2-
ethoxycarbonyl-2,3,4,5-tetrahydro-1H-3-benzazepine
(VIb). Yield 0.16 g (56%). Yellowish thick oily
substance. IR spectrum, ν, cm–1: 1727 (C=O). 1H NMR
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Stevenson, P.J., Tetrahedron Lett., 1988, vol. 29, p. 3993;
Hyett, D.J., Sweeney, J.B., Tavassoli, A., and Hayes, J.F.,
Tetrahedron Lett., 1997, vol. 38, p. 8283; Sweeney, J.B.,
Tavassoli, A., Carter, N.B., and Hayes, J.F., Tetrahedron.,
2002, vol. 58, p. 10113.
3
spectrum, δ, ppm: 1.16 t (3H, OCH2CH3, J 7.1 Hz),
2.40 s (3H, NCH3), 2.61 d (1H, H4, J 16.1 Hz), 2.95–
3.16 m (3H, H1,4), 3.53 d.d (1H, H2, J 7.0 and 3.3 Hz),
3.68 s (3H, OCH3), 3.72 s (3H, OCH3), 3.93 q (2H,
OCH2CH3, 3J 7.1 Hz), 6.65 s, 6.72 s (1H each, H6 and
H9). Mass spectrum: m/z 296 [M + 1]+. Found, %: N 4.75.
C16H21D2NO4. Calculated, %: N 4.74.
4,4-Dideutero-2-methyl-6,7-dimethoxy-1,2,3,4-
tetrahydroisoquinolinium 2-ethoxycarbonylmethyl-
ide (VIIb). Characterized by chromato-mass-spectro-
metry. Yield 6%. Mass spectrum: m/z 296 [M + 1]+.
3. Smith, S.Jr, Elango, V., and Shamma, M., J. Org. Chem.,
1984, vol. 49, p. 581.
4. Sato, Y., Shirai, N., Machida, Y., Ito, E., Yasui, T., Kurono,
Y., and Hatano, K., J. Org. Chem., 1992, vol. 57, p. 6711.
5. Shulgin, A. and Shulgin, A., PIHKAL. II. Berkeley:
Transform, Press, 1991, p. 593; Minatsakanyan, V.A. et
al., Sintezy geterotsiklicheskikh soedinenii (Synteses of
Heterocyclic Compounds),Aroyan,A.A., Ed., Erevan: Izd.
Akad. Nauk, ArmSSR, 1972, vol. 9, p. 40.
Ethyl deutero{[2-(1-deuterovinyl)-4,5-dimethoxy-
benzyl](methyl)amino}acetate (VIIIb). Yield 0.005 g
(2%), yellow oily substance. IR spectrum, ν, cm–1: 1739
1
(C=O). H NMR spectrum, δ, ppm: 1.13 t (3H,
3
OCH2CH3, J 7.2 Hz), 2.25 s (3H, NCH3), 3.65 s (2H,
ArCH2N), 3.71 s (1H, NCHDC=O), 3.75 s (3H, CH3O),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 5 2008