Dehydrogenation of 1-aryl(hetaryl)-1,2,3,4-tetrahydro-9H-β-carboline-3-carboxylic acids and their esters with dimethyl sulfoxide

Article abstract of DOI:10.1134/S1070428016110117

Oxidative dehydrogenation of 1-aryl(hetaryl)-1,2,3,4-tetrahydro-9Н-β-carboline-3-carboxylic acids derivatives with dimethyl sulfoxide leads to the formation of 1-aryl(hetaryl)-9Н-β-carbolines. Simultaneously with the dehydrogenation decarboxylation occurs

Full text of DOI:10.1134/S1070428016110117

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2016, Vol. 52, No. 11, pp. 1610–1615. © Pleiades Publishing, Ltd., 2016.
Original Russian Text © M.G. Abramyants, D.A. Lomov, T.I. Zavyazkina, 2016, published in Zhurnal Organicheskoi Khimii, 2016, Vol. 52, No. 11,
pp. 1617–1621.
Dehydrogenation of
1-Aryl(hetaryl)-1,2,3,4-tetrahydro-9H-β-carboline-3-carboxylic
Acids and Their Esters with Dimethyl Sulfoxide
M. G. Abramyants, D. A. Lomov,* and T. I. Zavyazkina
Litvinenko Institute of Physical Organic and Coal Chemistry, ul. R. Luxembourg 70, Donetsk, 83114 Ukraine
*e-mail: lomov_dmitrii@mail.ru
Received June 28, 2016
Abstract—Oxidative dehydrogenation of 1-aryl(hetaryl)-1,2,3,4-tetrahydro-9Н-β-carboline-3-carboxylic acids
derivatives with dimethyl sulfoxide leads to the formation of 1-aryl(hetaryl)-9Н-β-carbolines. Simultaneously
with the dehydrogenation decarboxylation occurs. At the oxidation with dimethyl sulfoxide of methyl 1-aryl
(hetaryl)-1,2,3,4-tetrahydro-9Н-β-carboline-3-carboxylicates methyl 1-aryl(hetaryl)-9Н-β-carboline-3-
carboxylates formed whose hydrolysis afforded the corresponding 1-aryl(hetaryl)-9Н-β-carboline-3-carboxylic
acids.
DOI: 10.1134/S1070428016110117
The oxidative properties of dimethyl sulfoxide are
known for a long time. They were discovered for the
first time at the oxidation of secondary alcohols to
ketones (Pfitzner–Moffatt oxidation) [1]. Later it has
been shown that this reaction can proceed in the
presence of oxalyl chloride (Swern oxidation) [2].
Subsequently the limits of the oxidative opportunities
of DMSO were considerably extended. It oxidizes
mercaptans to disulfides [3], isonitriles to the
corresponding isocyanates [4]. An oxidative amidation
using DMSO of α-ketoaldehydes with dialkylamines
was described [5]. Analogous reaction occurs as well
in the series of acetophenone derivatives [6]. All these
conversions occur selectively, and this is very
important in the presence of substituents sensitive to
the oxidation with the other reagents. This shows that
DMSO is simultaneously a mild and selective oxidizer
whose preparative possibilities call for further
investigation.
In continuation of the study of oxidative
aromatization of saturated heterocyclic systems under
treatment with DMSO we selected as objects of the
study 1-aryl(hetaryl)-1,2,3,4-tetrahydro-9Н-β-carboline-
3-carboxylic acids 1a–1f. The synthesis of compounds
1a–1d and 1f was described in [8], their stereoche-
mistry (cis- and trans-isomerism) were examined in [8,
9]. In many instances the isomers were isolated and
characterized. In the 1Н NMR spectra of isomers
chemical shifts of some protons are different [8, 10].
Compound 1e we synthesized by Pictet‒Spengler
reaction from tryptophan and pyridine-2-carbaldehyde.
In this case also a mixture of cis- and trans-isomers
was obtained that without separation was used in
1
subsequent transformations. The Н NMR spectrum of
compound 1e alongside the signals of aromatic protons
contained the proton signals of tetrahydropyridine ring
of its two isomers: multiplets at 2.92 and 3.14 ppm
(С4Н2), a quartet at 3.75 ppm (Н3), and a singlet at
5.22 ppm (Н1).
We found for the first time that DMSO is capable
of oxidizing heteroaromatic structures [7]. The heating
in DMSO of 4-aryl(hetaryl) spinacines in 8–10 h led to
the formation of 4-aryl(hetaryl)imidazo[4,5-с]pyri-
dines, in the presence of 1 equiv of LiOH they
converted in 4-aryl(hetaryl)imidazo[4,5-с]pyridine-6-
carboxylic acids. These processes are characterized by
a preparative simplicity and good yields [7].
At heating 1-aryl(hetaryl)-1,2,3,4-tetrahydro-9Н-β-
carboline-3-carboxylic acids 1a–1f in DMSO at 90–
95°С for 3–5 h they suffered dehydrogenation and
decarboxylation to afford 1-aryl-(hetaryl)-9Н-β-
carbolines 2a–2f in 58–81% yields (Scheme 1). In the
1Н NMR spectra of compounds 2a–2f (as compared
with the spectra of compounds 1a–1f) the signals of
1610

DEHYDROGENATION OF 1-ARYL(HETARYL)-1,2,3,4-TETRAHYDRO-9H-β-CARBOLINE-...
1611
Scheme 1.
COOH
COOH
N
N
NH
DMSO
DMSO
LiOH
Ar(Ht)
Ar(Ht)
Ar(Ht)
N
H
N
H
N
H
2a_2f
1a_1f
5a_5f
Ar(Ht) = Ph (a), 3-NO2Ph (b), 4-NO2Ph (c), 2-OHPh (d), 2-Py (e), 3-Py (f).
the protons of the tetrahydropyridine fragment at 2.77–
5.91 ppm disappeared, and signals appeared of the
vicinal protons of the pyridine fragment in the region
8.42–8.81 and 8.20–8.75 ppm.
cis- and trans-isomers signals appeared of the protons
of the methoxycarbonyl group each as three-proton
singlet at 3.73–3.81 and 3.83–3.88 ppm. In the
1
downfield region of the Н NMR spectra of some
esters 3a–3f overlapping occurs of the multiplets of the
aromatic protons of two isomers, whose integral
intensity corresponds to the aromatic protons in the
structure of obtained esters.
Unlike 4-aryl(hetaryl) spinacines [7], the heating of
lithium salts of compounds 1a–1f obtained in situ in
analogous conditions does not result in 1-aryl(hetaryl)-
9Н-β-carboline-3-carboxylic acids 5a–5f. Instead we
obtained the products of oxidative dehydrogenation
and decarboxylation, compounds 2a–2f. This may be
due to the fact that compounds 1a–1f are weaker acids
than 4-aryl(hetaryl) spinacines [11], and consequently
anions of compounds 1a–1f are less stable in solution.
The oxidation of esters 3a–3f was performed by
heating in DMSO at 90–95°С over 7–10 h. Com-
pounds 4a–4f were obtained in 40–81% yields. In the
1Н NMR spectra of methyl 1-aryl(hetaryl)-9Н-β-
carboline-3-carboxylates 4a–4f the signals of the
protons of the tetrahydropyridine fragment disap-
peared, and a singlet appeared from the proton in the
position 4 of the pyridine fragment in the region 8.90–
9.44 ppm. The doubling of the methoxycarbonyl
singlet also disappears, and it shifts downfield (3.97–
4.11 ppm) confirming as well the formation of esters
of aromatic carboxylic acids 4a–4f.
In order to prepare aromatic carboxylic acids 5a–5f
we synthesized methyl esters of acids 1a–1f. The
heating of compounds 1a–1f in methanol in the
presence of conc. H2SO4 at 70°С for 4–5 h led to the
formation of methyl 1-aryl(hetaryl)-1,2,3,4-tetrahydro-
9Н-β-carboline-3-carboxylates 3a–3f in 62–83% yield
[12] (Scheme 2). Compounds 3a–3f unlike 1a–1f are
readily soluble in chloroform, and it was utilized for
their purification. The obtained esters were isolated as
a mixture of two isomers that was used in further
transformations without separation.
Hydrolysis of compounds 4a–4f was carried out in
water-alcoholic solution of alkali by heating for 3–4 h
[13]. On distilling off the alcohol and acidifying the
residue with 6 N HCl to рН 4–5 we isolated carboxylic
1
In the 1Н NMR spectra of esters 3a–3f as compared
to the spectra of initial acids 1a–1f along with the
proton signals of the tetrahydropyridine fragment of
acids 5a–5f in 52–86% yields. In their Н NMR
spectra the proton signal from the methoxycarbonyl
group disappeared.
Scheme 2.
COOMe
NH
COOMe
N
COOH
N
_
MeOH
H+
DMSO
OH
1a_1f
Ar(Ht)
Ar(Ht)
Ar(Ht)
N
H
N
H
N
H
3a_3f
4a_4f
5a_5f
Ar(Ht) = Ph (a), 3-NO2Ph (b), 4-NO2Ph (c), 2-OHPh (d), 2-Py (e), 3-Py (f).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 11 2016

ABRAMYANTS et al.
1612
Hence, DMSO oxidized 1-aryl(hetaryl)-1,2,3,4-
(1Н, Н6), 7.55 m (2Н, Н7, Н1'), 7.62 m (3Н, Н2',4′,5′),
7.98 m (3Н, Н5, Н8, Н3'), 8.20 d (1Н, Н4, J 8.0 Hz),
8.61 d (1Н, Н3, J 4.0 Hz). Found, %: C 83.51; H 4.99;
N 11.43. C17H12N2. Calculated, %: C 83.58; H 4.95; N
11.47.
tetrahydro-9Н-β-carboline-3-carboxylic acids 1a–1f to
the corresponding 1-aryl(hetaryl)-9Н-β-carbolines 2a–
2f. Methyl esters of 1-aryl-(hetaryl)-1,2,3,4-tetrahydro-
9Н-β-carboline-3-carboxylic acids 3a–3f were
oxidized by DMSO to methyl esters of 1-aryl(hetaryl)-
9Н-β-carboline-3-carboxylic acids 4a–4f.
1-(3-Nitrophenyl)-9Н-β-carboline (2b). Yield
1
58%, mp 173–175°С. Н NMR spectrum (DMSO-d6),
δ, ppm: 7.38 t (1Н, Н6), 7.70 m (2Н, Н5, Н4'), 7.98 t
(1Н, Н7), 8.43 d (1Н, Н8, J 8.0 Hz), 8.46 m (2Н, Н2',3′),
8.52 d (1Н, Н4, J 8.0 Hz), 8.61 d (1Н, Н3, J 4.0 Hz),
8.83 s (1Н, Н1'), 12.20 s (1Н, NН). Found, %: C 70.51;
H 3.89; N 14.44. C17H11N3О2. Calculated, %: C 70.58;
H 3.83; N 14.53.
EXPERIMENTAL
1Н NMR spectra were registered on a spectrometer
Bruker Avance II 400 at operating frequency 400 MHz,
internal reference TMS. The homogeneity of synthesi-
zed compounds was checked by TLC on Silufol UV-
254 plates, (eluent a mixture methanol–chloroform,
1 : 10, development in iodine vapor or under UV
radiation).
1-(4-Nitrophenyl)-9Н-β-carboline (2c). Yield
1
81%, mp 180–182°С. Н NMR spectrum (DMSO-d6),
δ, ppm: 7.38 t (1Н, Н6), 7.60 m (2Н, Н5, Н7), 8.04 d
(1Н, Н8, J 4.0 Hz), 8.20 d (2Н, Н1',5′, J 8.0 Hz), 8.23 d
(1Н, Н4, J 8.0 Hz), 8.45 d (2Н, Н2',4′, J 8.0 Hz), 8.63 d
(1Н, Н3, J 4.0 Hz). Found, %: C 70.53; H 3.88; N
14.46. C17H11N3О2. Calculated, %: C 70.58; H 3.83; N
14.53.
1-(Pyridin-2-yl)-1,2,3,4-tetrahydro-9Н-β-carboli-
ne-3-carboxylic acid (1e). A mixture of 2.04 g
(1 mmol) of L-tryptophan, 1.18 g (1.1 mmol) of
pyridine-2-carbaldehyde, 10 mL of 1 N sulfuric acid,
30 mL of water, and 5 mL of ethanol was boiled at
stirring for 10 h. The separated precipitate was filtered
off, washed with ethanol, dried, and recrystallized
from aqueous ethanol. The reaction product was a
mixture of two spatial isomers А and В. Yield 73%,
mp 236–238°С (decomp.).
2-(9Н-β-carbolin-1-yl)phenol (2d). Yield 71%,
1
mp 200–202°С. Н NMR spectrum (DMSO-d6), δ,
ppm: 7.05 m (2Н, Н4',5′), 7.30 t (1Н, Н3'), 7.37 t (1Н,
Н6), 7.59 t (1Н, Н7), 7.72 d (1Н, Н5, J 8.0 Hz), 8.06 d
(1Н, Н8, J 8.0 Hz), 8.22 d (1Н, Н2', J 8.0 Hz), 8.31 d
(1Н, Н4, J 8.0 Hz), 8.42 d (1Н, Н3, J 4.0 Hz), 11.62 s
(1Н, NН). Found, %: C 78.40; H 4.68; N 10.71.
C17H12N2О. Calculated, %: C 78.44; H 4.65; N 10.76.
1
Isomer А. Н NMR spectrum (DMSO-d6), δ, ppm:
2.92 m (2Н, C4H2), 3.75 q (1Н, H3), 5.22 s (1Н, Н1),
6.94 d (1Н, Н5, J 4.0 Hz), 7.25 d (1Н, Н8, J 4.0 Hz),
7.43 m (2Н, Н6, Н7), 7.54 d (1Н, Н1', J 8.0 Hz), 7.68 t
(1Н, Н3'), 7.79 t (1Н, Н2′), 7.94 d (1Н, Н4′, J 8.0 Hz),
10.22 s (1Н, N9H).
1-(Pyridin-2-yl)-9Н-β-carboline (2e). Yield 71%,
1
mp 173–175°С. Н NMR spectrum (CDCl3), δ, ppm:
7.31 t (1Н, Н6), 7.35 t (1Н, Н7), 7.59 t (1Н, Н3'), 7.65 d
(1Н, Н5, J 8.0 Hz), 7.91 t (1Н, Н4'), 8.01 d (1Н, Н8, J
4.0 Hz), 8.18 d (1Н, Н5', J 8.0 Hz), 8.55 d (1Н, Н2', J
4.0 Hz), 8.75 d (1Н, Н4, J 8.0 Hz), 8.81 d (1Н, Н3, J
4.0 Hz), 11.39 s (1Н, NН). Found, %: C 78.30; H 4.57;
N 17.08. C16H11N3. Calculated, %: C 78.35; H 4.52; N
17.13.
1
Isomer В. Н NMR spectrum (DMSO-d6), δ, ppm:
3.14 m (2Н, C4H2), 3.75 q (1Н, H3), 5.22 s (1Н, Н1),
7.01 d (1Н, Н5, J 4.0 Hz), 7.27 d (1Н, Н8, J 4.0 Hz),
7.41 m (2Н, Н6, Н7), 7.58 d (1Н, Н1', J 8.0 Hz), 7.85 m
(2Н, Н2',3'), 8.02 d (1Н, Н4′, J 8.0 Hz), 10.66 s (1Н,
N9H). Found, %: C 69.57; H 5.17; N 14.30.
C17H15N3O2. Calculated, %: C 69.61; H 5.15; N14.33.
1-(Pyridin-3-yl)-9Н-β-carboline (2f). Yield 71%,
1
mp 148–150°С. Н NMR spectrum (CDCl3), δ, ppm:
7.35 t (1Н, Н6), 7.58 m (3Н, Н5, Н7, Н5'), 8.04 d (1Н,
Н8, J 8.0 Hz), 8.21 d (1Н, Н6', J 8.0 Hz), 8.39 d (1Н,
Н4, J 8.0 Hz), 8.62 d (1Н, Н4', J 4.0 Hz), 8.68 d (1Н,
Н3, J 4.0 Hz), 9.41 s (1Н, Н2'), 10.01 s (1Н, NН).
Found, %: C 78.28; H 4.56; N 17.07. C16H11N3.
Calculated, %: C 78.35; H 4.52; N 17.13.
Compounds 2a–2f. In 5–7 mL of DMSO was
dissolved 1 mmol of 1-aryl(hetaryl)-1,2,3,4-tetrahydro-
9Н-β-carboline-3-carboxylic acid 1а–1f, and the
solution was heated at 90–95°С for 3–5 h. Excess
DMSO was distilled off in a vacuum, the residue was
recrystallized from aqueous ethanol.
Compounds (3a–3f). A mixture of 1 mmol of acid
1a–1f, 5 mmol of anhydrous methanol, and 0.2 mmol
1-Phenyl-9Н-β-carboline (2а). Yield 60%, mp 215–
217°С. Н NMR spectrum (CDCl3), δ, ppm: 7.35 t
1
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DEHYDROGENATION OF 1-ARYL(HETARYL)-1,2,3,4-TETRAHYDRO-9H-β-CARBOLINE-...
1613
of conc. sulfuric acid was boiled excluding moisture
for 4–5 h. On distilling off methanol the residue was
poured in a 5-fold volume of ice water and neutralized
with a concentrated solution of sodium carbonate. The
separated precipitate was filtered off, washed with
water, and dried. From the dry residue the product was
extracted with chloroform, chloroform was distilled off
to dryness, the residue was recrystallized from
methanol. Obtained esters were mixtures of two spatial
isomers А and В.
Isomer В. 1Н NMR spectrum (CDCl3), δ, ppm: 3.17
m (2Н, С4Н2), 3.85 s (3Н, СН3О), 4.02 q (1Н, Н3),
5.41 s (1Н, Н1), 7.17–7.24 m (2Н, Н6, Н7), 7.51–7.53
m (2Н, Н5, Н8), 7.63 d (2Н, Н1',5′, J 8.0 Hz), 8.25 d
(2Н, Н2',4′, J 8.0 Hz). Found, %: C 78.31; H 4.56; N
17.10. C19H18N3О4. Calculated, %: C 78.35; H 4.52; N
17.13.
Methyl 1-(2-hydroxyphenyl)-1,2,3,4-tetrahydro-
9Н-β-carboline-3-carboxylate (3d). Yield 66%, mp
156–158°С (a mixture of isomers) {189–192°С (cis-
isomer), 168–169°С (trans-isomer) [14]}.
Isomer А. 1Н NMR spectrum (CDCl3), δ, ppm: 3.32
m (2Н, С4Н2), 3.74 s (3Н, СН3О), 4.14 t (1Н, Н3), 5.61
s (1Н, Н1), 6.85–6.95 m (3Н, Н6, Н7, Н3'), 7.13–7.17 m
(3Н, Н5, Н8, Н4'), 7.22 d (1Н, Н5', J 8.0 Hz), 7.53 d
(1Н, Н2', J 8.0 Hz).
Isomer В. 1Н NMR spectrum (CDCl3), δ, ppm: 3.32
m (2Н, С4Н2), 3.88 s (3Н, СН3О), 3.95 t (1Н, Н3), 5.38
s (1Н, Н1), 6.85–6.95 m (3Н, Н6, Н7, Н3'), 7.13–7.17 m
(3Н, Н5, Н8, Н4'), 7.22 d (1Н, Н5', J 8.0 Hz), 7.53 d
(1Н, Н2', J 8.0 Hz). Found, %: C 70.75; H 5.67; N
8.64. C19H18N2О3. Calculated, %: C 70.79; H 5.63; N
8.69.
Methyl 1-phenyl-1,2,3,4-tetrahydro-9Н-β-carbo-
line-3-carboxylate (3а). Yield 71%, mp 165–167°С (a
mixture of isomers) {201–203°С (cis-isomer), 175–
177°С (trans-isomer) [14]}.
Isomer А. 1Н NMR spectrum (CDCl3), δ, ppm: 3.27
m (2Н, С4Н2), 3.86 s (3Н, СН3О), 3.99 t (1Н, Н3), 5.26
s (1Н, Н1), 7.16–7.18 m (2Н, Н5, Н6), 7.34 d (1Н, Н7, J
4.0 Hz), 7.39 s (5Н, Н1'–5′).
Isomer В. 1Н NMR spectrum (CDCl3), δ, ppm: 3.13
m (2Н, С4Н2), 3.73 s (3Н, СН3О), 3.99 t (1Н, Н3), 5.43
s (1Н, Н1), 7.16–7.18 m (2Н, Н5, Н6), 7.35 d (1Н, Н7, J
4.0 Hz), 7.48–7.62 m (5Н, Н1'–5′). Found, %: C 74.45;
H 5.97; N 9.10. C19H18N2О2. Calculated, %: C 74.49;
H 5.92; N 9.14.
Methyl 1-(pyridin-2-yl)-1,2,3,4-tetrahydro-9Н-β-
carboline-3-carboxylate (3e). Yield 83 %, mp 154–
156°С (a mixture of isomers).
Isomer А. 1Н NMR spectrum (CDCl3), δ, ppm: 3.49
m (2Н, С4Н2), 3.81 s (3Н, СН3О), 4.05 q (1Н, Н3),
5.54 s (1Н, Н1), 7.65–7.72 m (3Н, Н6, Н7, Н3'), 7.92–
7.94 m (2Н, Н5, Н8), 8.56 d (1Н, Н1', J 4.0 Hz), 8.83 d
(1Н, Н4', J 8.0 Hz).
Isomer В. 1Н NMR spectrum (CDCl3), δ, ppm: 3.51
m (2Н, С4Н2), 3.88 s (3Н, СН3О), 4.25 q (1Н, Н3),
5.43 s (1Н, Н1), 7.32–7.38 m (3Н, Н6, Н7, Н3'), 7.92–
7.94 m (2Н, Н5, Н8), 8.04 d (1Н, Н1', J 8.0 Hz), 8.75 d
(1Н, Н4', J 8.0 Hz). Found, %: C 70.30; H 5.62; N
13.65. C18H17N3О2. Calculated, %: C 70.34; H 5.58; N
13.67.
Methyl 1-(3-nitrophenyl)-1,2,3,4-tetrahydro-9Н-
β-carboline-3-carboxylate (3b). Yield 69%, mp 188–
190°С (a mixture of isomers).
Isomer А. 1Н NMR spectrum (CDCl3), δ, ppm: 3.35
m (2Н, С4Н2), 3.85 s (3Н, СН3О), 4.02 t (1Н, Н3), 5.57
s (1Н, Н1), 7.15–7.20 m (2Н, Н5, Н6), 7.38–7.41 m
(1Н, Н7), 7.49–7.59 m (3Н, Н8, Н4',5′), 7.78 d (1Н, Н3',
J 8.0 Hz), 8.31 s (1Н, Н1').
Isomer В. 1Н NMR spectrum (CDCl3), δ, ppm: 3.29
m (2Н, С4Н2), 3.74 s (3Н, СН3О), 4.00 t (1Н, Н3), 5.42
s (1Н, СН1), 7.15–7.20 m (2Н, Н5, Н6), 7.38–7.41 m
(1Н, Н7), 7.49–7.59 m (3Н, Н8, Н4',5′), 7.68 d (1Н, Н3',
J 8.0 Hz), 8.25 s (1Н, Н1'). Found, %: C 64.90; H 4.90;
N 11.90. C19H17N3О4. Calculated, %: C 64.95; H 4.88;
N 11.96.
Methyl 1-(pyridin-3-yl)-1,2,3,4-tetrahydro-9Н-β-
carboline-3-carboxylate (3f). Yield 64%, mp 177–
179°С (a mixture of isomers) {234–236°С (cis-
isomer), 213–215°С (trans-isomer) [8]}.
Methyl 1-(4-nitrophenyl)-1,2,3,4-tetrahydro-9Н-
β-carboline-3-carboxylate (3c). Yield 62%, mp 166–
168°С (a mixture of isomers) (173–174°С [15]).
Isomer А. 1Н NMR spectrum (CDCl3), δ, ppm: 3.29
m (2Н, С4Н2), 3.74 s (3Н, СН3О), 3.95 t (1Н, Н3), 5.56
s (1Н, СН1), 7.17–7.24 m (2Н, Н6, Н7), 7.51–7.53 m
(2Н, Н5, Н8), 7.58 d (2Н, Н1',5′, J 8.0 Hz), 8.20 d (2Н,
Isomer А. 1Н NMR spectrum (CDCl3), δ, ppm: 3.23
m (2Н, С4Н2), 3.74 s (3Н, СН3О), 3.99 q (1Н, Н3),
5.49 s (1Н, Н1), 7.15–7.19 m (2Н, Н6, Н7), 7.59 m
(2Н, Н5, Н8), 8.41– 8.52 m (3Н, Н3'-5′), 8.62 s (1Н,
Н1').
Н
2',4′, J 8.0 Hz).
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ABRAMYANTS et al.
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Isomer B. 1Н NMR spectrum (CDCl3), δ, ppm: 3.08
7.92 d (1Н, Н8, J 4.0 Hz), 8.04 d (1Н, Н1', J 4.0 Hz),
8.18‒8.25 m (2Н, Н2',3′), 8.57 d (1Н, Н4', J 8.0 Hz),
8.95 s (1Н, Н4). Found, %: C 71.20; H 4.37; N 13.78.
C18H13N3О2. Calculated, %: C 71.28; H 4.32; N 13.85.
m (2Н, С4Н2), 3.85 s (3Н, СН3О), 3.99 q (1Н, Н3),
5.31 s (1Н, Н1), 7.15–7.19 m (2Н, Н6, Н7), 7.59 m
(2Н, Н5, Н8), 7.72 d (1Н, Н5', J 8.0 Hz), 8.41–8.52 m
(2Н, Н3',4′), 8.55 s (1Н, Н1'). Found, %: C 70.27; H
5.63; N 13.61. C18H17N3О2. Calculated, %: C 70.34; H
5.58; N 13.67.
Methyl 1-(pyridin-3-yl)-9Н-β-carboline-3-
carboxylate (4f). Yield 81%, mp 250–252°С (252–
254°С [17]). 1Н NMR spectrum (CDCl3), δ, ppm: 4.09
s (3Н, CH3O), 7.40 t (1Н, Н6), 7.48 t (1Н, Н7), 7.56–
7.63 m (2Н, Н3',4′), 8.26 d (1Н, Н5, J 4.0 Hz), 8.40 d
(1Н, Н8, J 4.0 Hz), 8.56 d (1Н, Н5', J 4.0 Hz), 8.96 s
(1Н, Н4), 9.44 s (1Н, Н1'), 11.47 s (1Н, NН). Found,
%: C 71.21; H 4.39; N 13.77. C18H13N3О2. Calculated,
%: C 71.28; H 4.32; N 13.85.
Compounds 4a–4f. In 5 mL of DMSO was
dissolved 1 mmol of compound 3a–3f, and the solution
was heated at 90–95°С for 7–10 h. Excess DMSO was
distilled off in a vacuum, the residue was recrystallized
from methanol.
Methyl 1-phenyl-9Н-β-carboline-3-carboxylate
1
(4а). Yield 70%, mp 250–252°С (mp 253°С [16]). Н
Compounds 5a–5f. A mixture of 1 mmol of
compound 4a–4f, 5 mL of ethanol, and 2 mL of 20%
water solution of KОН was boiled for 3–5 h. On
removing the alcohol the residue was acidified with
6 N HCl to рН 4–5. The separated precipitate was
filtered off and recrystallized from water.
NMR spectrum (CDCl3), δ, ppm: 4.07 s (3Н, CH3O),
7.40 t (1Н, Н6), 7.52 t (1Н, Н7), 7.58 m (5Н, Н1'–5′),
7.97 d (1Н, Н5, J 8.0 Hz), 8.24 d (1Н, Н8, J 8.0 Hz),
8.90 s (1Н, Н4). Found, %: C 75.41; H 4.71; N 9.23.
C19H14N2О2. Calculated, %: C 75.48; H 4.67; N 9.27.
Methyl 1-(3-nitrophenyl)-9Н-β-carboline-3-
carboxylate (4b). Yield 40%, mp 309–311°С. Н
1-Phenyl-9Н-β-carboline-3-carboxylic acid (5а).
Yield 58%, mp > 300°С (decomp.) {mp 283–284°С
1
1
NMR spectrum (DMSO-d6), δ, ppm: 3.95 s (3Н,
CH3O), 7.36 d (1Н, Н5, J 8.0 Hz), 7.65‒7.69 m (2Н,
Н6, Н7), 7.93 d (1Н, Н8, J 8.0 Hz), 8.45‒8.48 m (3Н,
Н3'-5′), 8.77 s (1Н, Н4), 9.00 s (1Н, Н1'), 12.14 s (1Н,
NН). Found, %: C 65.65; H 3.80; N 12.03.
C19H13N3О4. Calculated, %: C 65.70; H 3.77; N 12.10.
(decomp.) [15]}. Н NMR spectrum (CDCl3), δ, ppm:
7.25 t (1Н, Н6), 7.56 m (4Н, Н7, Н2'–4′), 7.64 d (1Н, Н5,
J 8.0 Hz), 7.99 m (2Н, H8, Н1'), 8.26 d (1Н, Н5', J
8.0 Hz), 8.81 s (1Н, Н4), 11.60 s (1Н, NН). Found, %:
C 74.92; H 4.27; N 9.68. C18H12N2О2. Calculated, %:
C 74.99; H 4.20; N 9.72.
Methyl 1-(4-nitrophenyl)-9Н-β-carboline-3-car-
boxylate (4c). Yield 70%, mp 173–175°С. Н NMR
1-(3-Nitrophenyl)-9Н-β-carboline-3-carboxylic
1
1
acid (5b). Yield 53%, mp > 300°С (decomp.). Н
spectrum (CDCl3), δ, ppm: 4.09 s (3Н, CH3O), 7.19 t
(1Н, Н6), 7.43 t (1Н, Н7), 7.57 d (1Н, Н5, J 8.0 Hz),
7.68 d (1Н, Н8, J 4.0 Hz), 8.11 d (2Н, Н1',4′, J 8.0 Hz),
8.25 d (2Н, Н2',3′, J 8.0 Hz), 8.92 s (1Н, Н4). Found, %:
C 65.63; H 3.83; N 11.98. C19H13N3О4. Calculated, %:
C 65.70; H 3.77; N 12.10.
NMR spectrum (DMSO-d6), δ, ppm: 7.28 t (1Н, Н6),
7.62 t (1Н, Н7), 7.65 d (1Н, Н5, J 4.0 Hz), 7.89 m (2Н,
Н8, Н5'), 8.33 t (1Н, Н4'), 8.48 d (1Н, Н3', J 8.0 Hz),
8.74 s (1Н, Н4), 8.83 s (1Н, Н1'), 11.77 s (1Н, NН).
Found, %: C 64.80; H 3.39; N 12.57. C18H11N3О4.
Calculated, %: C 64.86; H 3.33; N 12.61.
Methyl 1-(2-hydroxyphenyl)-9Н-β-carboline-3-car-
boxylate (4d). Yield 76%, mp 233–235°С. Н NMR
1-(4-Nitrophenyl)-9Н-β-carboline-3-carboxylic
1
1
acid (5c). Yield 52%, mp 295–297°С (decomp.). Н
spectrum (DMSO-d6), δ, ppm: 3.97 s (3Н, CH3O), 7.05‒
7.09 m (2Н, Н3',4′), 7.36‒7.44 m (2Н, Н6, Н7), 7.64 d
(1Н, Н5, J 4.0 Hz), 7.75 d (1Н, Н8, J 4.0 Hz), 8.05 d
(1Н, Н5', J 8.0 Hz), 8.47 d (1Н, Н2', J 8.0 Hz), 8.98 s
(1Н, Н4), 12.04 s (1Н, NН), 13.04 s (1Н, ОН). Found,
%: C 71.61; H 4.47; N 8.72. C19H14N2О3. Calculated,
%: C 71.69; H 4.43; N 8.80.
NMR spectrum (DMSO-d6), δ, ppm: 7.36 t (1Н, Н6),
7.64 t (1Н, Н7), 7.71 d (1Н, Н5, J 8.0 Hz), 8.37 d (2Н,
Н1',5′, J 8.0 Hz), 8.47 d (2Н, Н2',4′, J 8.0 Hz), 8.49 d
(1Н, Н8, J 8.0 Hz), 9.00 s (1Н, Н4), 12.14 s (1Н, NН).
Found, %: C 64.77; H 3.38; N 12.54. C18H11N3О4.
Calculated, %: C 64.86; H 3.33; N 12.61.
1-(2-Hydroxyphenyl)-9Н-β-carboline-3-carbo-
xylic acid (5d). Yield 86%, mp 278–280°С (decomp.).
1Н NMR spectrum (DMSO-d6), δ, ppm: 7.05–7.08 m
(2Н, Н1',2′), 7.32‒7.41 m (2Н, Н6, Н3'), 7.62 t (1Н, Н7),
7.77 d (1Н, Н5, J 8.0 Hz), 8.13 d (1Н, Н8, J 8.0 Hz),
Methyl 1-(pyridin-2-yl)-9Н-β-carboline-3-carbo-
1
xylate (4e). Yield 70%, mp 181–182°С. Н NMR
spectrum (CDCl3), δ, ppm: 4.11 s (3Н, CH3O), 7.38 t
(1Н, Н6), 7.60 t (1Н, Н7), 7.65 d (1Н, Н5, J 4.0 Hz),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 11 2016

DEHYDROGENATION OF 1-ARYL(HETARYL)-1,2,3,4-TETRAHYDRO-9H-β-CARBOLINE-...
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8.43 d (1Н, Н4', J 8.0 Hz), 8.94 s (1Н, Н4), 12.05 s
(1Н, NН). Found, %: C 71.00; H 4.02; N 9.17.
C18H12N2О3. Calculated, %: C 71.05; H 3.97; N 9.21.
5. Mupparapu, N., Khan, S., Battula, S., Kushwaha, M.,
Gupta, A.P., Ahmed, Q.N., and Vishwakarma, R.A.,
Org. Lett., 2014, vol. 16, p. 1152.
6. Wu, X., Gao, Q., Liu, S., and Wu, A., Org. Lett., 2014,
1-(Pyridin-2-yl)-9Н-β-carboline-3-carboxylic
acid (5e). Yield 60%, mp >300°С (decomp.). 1Н NMR
spectrum (DMSO-d6), δ, ppm: 7.27 t (1Н, Н6), 7.51 d
(1Н, Н5, J 8.0 Hz), 7.57 t (1Н, Н7), 7.85 d (1Н, Н8, J
8.0 Hz), 8.02 t (1Н, Н3'), 8.32 d (1Н, Н1', J 8.0 Hz),
8.68 d (1Н, Н4', J 8.0 Hz), 8.85 s (1Н, Н4), 8.87 t (1Н,
Н3'), 11.95 s (1Н, NН). Found, %: C 70.50; H 3.85; N
14.47. C17H11N3О2. Calculated, %: C 70.58; H 3.83; N
14.53.
vol. 16, p. 2888.
7. Lomov, D.A., Abramyants, M.G., Astashkina, N.V.,
Korotkikh, N.I., and Gres’ko, S.V., Russ. J. Org. Chem.,
2014, vol. 50, p. 1039.
8. Ungemach, F., Soerens, D., Weber, R., DiPierro, M.,
Campos, O., Mokry, P., Cook, J.M., and Silverton, J.V.,
J. Am. Chem. Soc., 1980, vol. 102, p. 6976.
9. Toth, G., Szantay, J.C., Kalaus, G., Thaler, G., and
Snatzke, G., J. Chem. Soc., Perkin. Trans. 2, 1989,
p. 1849.
1-(Pyridin-3-yl)-9Н-β-carboline-3-carboxylic
acid (5f). Yield 63%, mp >300°С (decomp.). 1Н NMR
spectrum (DMSO-d6), δ, ppm: 7.33 t (1Н, Н6), 7.59–
7.70 m (3Н, Н5, Н7, Н8), 8.41‒8.46 m (2Н, Н4',5′), 8.74
d (1Н, Н3', J 4.0 Hz), 8.95 s (1Н, Н4), 9.25 s (1Н, Н1'),
12.11 s (1Н, NН). Found, %: C 70.49; H 3.88; N
14.42. C17H11N3О2. Calculated, %: C 70.58; H 3.83; N
14.53.
10. Bailey, P.D. and Hollinshead, S.P., J. Chem. Soc. Chem.
Commun., 1985, p. 1575.
11. Braibanti, A., Dallavalle, F., Leporati, E., and Mori, G.,
J. Chem. Soc., Dalton Trans., 1973, p. 323.
12. Organikum, Moscow: Mir, 2008, vol. 2, p. 76.
13. Organikum, Moscow: Mir, 2008, vol. 2, p. 93.
14. Soerens, D., Sandrin, J., Ungemach, F., Mokry, P.,
Wu, G.S., Yamanaka, E., Hutchins, L., DiPierro, M.,
and Cook, J.M., J. Org. Chem., 1979, vol. 44, p. 535.
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