Metal free one pot synthesis of Β-carbolines via a domino Pictet-Spengler reaction and aromatization

Article abstract of DOI:10.1016/j.mcat.2019.02.018

A convenient and efficient metal free, atom economical flexible synthesis of β-carbolines involving a domino Pictet-Spengler reaction and aromatization in oxygen atmosphere in N-methyl-2-pyrollidone (NMP) is described. Variety of aryl, heteroaryl and aliphatic aldehydes were found to be good substrates for this methodology. Several β-carbolines (6a-6t) and β-carboline methyl esters (7a-7e) were synthesized using this methodology.The same reaction carried out in argon atmosphere in the presence of catalytic amount of acid in NMP furnished, tetrahydro-β-carbolines (4a-4g).

Full text of DOI:10.1016/j.mcat.2019.02.018

Molecular Catalysis 468 (2019) 86–93
Contents lists available at ScienceDirect
Molecular Catalysis
journal homepage: www.elsevier.com/locate/mcat
Metal free one pot synthesis of β-carbolines via a domino Pictet-Spengler
reaction and aromatization
S. Ramua,1, S. Srinatha,1, A. Aswin kumar , B. Baskar , K. Ilangob,c,⁎, K.K. Balasubramaniand
a
a,⁎
a
Laboratory of Sustainable Chemistry, Department of Chemistry, SRM Institute of Science and Technology, Kattankulatur, 603 203, Kancheepuram (Dt), Tamilnadu, India
Interdisciplinary Institute of Indian System of Medicine (IIISM), SRM Institute of Science and Technology, Kattankulathur 603 203, Kancheepuram (Dt), Tamilnadu,
b
India
c
Department of Pharmaceutical Chemistry, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur 603 203, Kancheepuram (Dt),
Tamilnadu, India
d
Department of Biotechnology, Indian Institute of Technology Madras, Adyar, Chennai, 600 036, Tamilnadu, India
A R T I C L E I N F O
A B S T R A C T
Keywords:
A convenient and efficient metal free, atom economical flexible synthesis of β-carbolines involving a domino
Pictet-Spengler reaction and aromatization in oxygen atmosphere in N-methyl-2-pyrollidone (NMP) is described.
Variety of aryl, heteroaryl and aliphatic aldehydes were found to be good substrates for this methodology.
Several β-carbolines (6a-6t) and β-carboline methyl esters (7a-7e) were synthesized using this methodology.The
same reaction carried out in argon atmosphere in the presence of catalytic amount of acid in NMP furnished,
tetrahydro-β-carbolines (4a-4g).
Tetrahydro-β-carbolines
β-Carboline
Pictet-Spengler Cylization
Aromatization
Domino reaction
1. Introduction
presence of a Bronsted or Lewis acid catalyst. The second stage is the
acid catalysed cyclisation of the imine to form the tetrahydro-β-car-
The β-carboline motif constitutes an important structural unit in a
boline (Scheme 1a). The imines can be isolated or in situ prepared and
subjected to the cyclisation to afford the tetrahydro-β-carboline. A
variety of Bronsted acids [9] and Lewis acids [10] have been reported
for Pictet-Spengler reaction. Recently Wang et al. had reported that
Pictet-Spengler reaction could be realized in weakly acidic solvent
1,1,1,3,3,3-hexafluoro-2-propanol to form tetrahydro-β-carboline [6f]
without the need to isolate the imine. Till date there is no report on one
pot metal free or acid free Pictet-Spengler reaction of tryptamines with
aldehydes to form directly β-carbolines. The existing methods require
preformed tetrahydro-β-carbolines by using a set of conditions and then
subjecting them to aromatisation employing different conditions using
a variety of reagents. Aromatisation oftetrahydro-β-carbolines is carried
out by heating them with Pd on C [11] or S [12] or in high boiling
hydrocarbons solvents for long hours or treating with excess of oxi-
wide range of natural products (Fig. 1) and synthetic congeners [1].
Compounds derived from this ring system exhibit a wide range of
biological properties including antimalarial [2], antitumor [3], and
anti-HIV activities [4]. Some of them have received attention as dia-
zepam antagonists. Others show potent binding affinities toward ben-
zodiazepine receptors in the central nervous system, thereby acting as
diazepam antagonists [5].
In the light of the importance of β-carbolines, mild and efficient
synthetic methods for the construction of the β-carboline unit are de-
sirable. While several methods are known
for the construction of β-carboline framework, the one based on
dehydrogenation of 1,2,3,4-tetrahydro-β-carboline offers a direct and
quick entry as they are easier to access by Pictet-Spengler reaction [[6]]
(
Scheme 1). It may be noted that tetrahydro-β-carboline themselves are
2 2
dizing agents like SeO [13] or MnO [14] or potassium permanganate
[15] athightemperature have been employed. Most of these methods
require harsh conditions. Chloranil, [16] DDQ [17], trichloroisocy-
an important class of condensed heterocycles, present in many bioac-
tive natural products such as Fumitremorgin C and Neonaucleoside A
and C. [7] They are known to display a broad spectrum of biological
activities [8]. The Pictet-Spengler reaction involves two stages. The
first stage is the formation of the imine intermediate from the reaction
of an electron rich β-arylethylamine with an aldehyde or a ketone in the
2
anuric acid [18], PhI(OAc) [19], N-chlorosuccinimide [20] (NCS) and
6
IBX [21] have also been used to bring about aromatization but these
methods suffer from disadvantages such as use of excess reagents,
stoichiometric waste generation, poor yields or lack of general
⁎
Corresponding authors.
E-mail addresses: baskar.b@ktr.srmuniv.ac.in (B. Baskar), ilangok67@gmail.com (K. Ilango).
These authors are contributed equally to this work.
1
https://doi.org/10.1016/j.mcat.2019.02.018
Received 3 January 2019; Received in revised form 14 February 2019; Accepted 18 February 2019
2468-8231/ © 2019 Elsevier B.V. All rights reserved.

S. Ramu, et al.
Molecular Catalysis 468 (2019) 86–93
Fig. 1. Examples of naturally occurring β-carbolines.
(
1
Table 1, entry 1). When the reaction mixture was heated at 120 °C for
2 h., we were gratified to note that the reaction resulted in the for-
mation of the Pictet-Spengler product, viz., tetrahydro-β-carboline 4a
Table 1, entry 2). To our surprise, heating a mixture of tryptamine with
aldehyde at 130 °C for 24 h, led to the completely aromatized product
a viz. 1-(4-nitrophenyl)-9H-pyrido[3,4-b]indole (Table 1, entry 3) in
very good yield (85%). The structure of the product was confirmed by
(
6
1
13
H and C NMR spectroscopy. The spectral data and melting point of
this product were in agreement with those reported in the literature
20]. This domino transformation involving imine formation, Pictet-
[
Spengler reaction and aromatization inspired us to screen a few more
solvents in order to identify the best solvent system. Among the eight
different solvents and conditions examined (Table 1, entries 4–11),
NMP was found to be the most suitable solvent. It is interesting to note
that under similar conditions in DMF as the solvent, although 6a was
formed the conversion was only moderate (55%) (Table 1, entry 4).
DMSO and chlorobenzene
also, were found to be no better (Table 1, entry 5–6).Moreover, the
generation of foul smelling from dimethyl sulphide in DMSO reaction
which is highly flammable and irritant to eyes and skin is a serious
concern.In contrast, there was no reaction in poly ethylene glycol 200
at 130 °C for 24 h, while in toluene at 111 °C for 24 h, the formation of
the imine 3a (˜70%) with 4a (˜19%) (Table 1, entry 7) was observed.
Also of interest is the finding that under our conditions, the reaction
does not stop at dihydro-β-carboline stage (5a) whereas Feng et al. had
reported that in the case of 1-aryltetrahydroisoquinolines, heating them
in DMF at 120 °C for 24 h led to the 3,4-dihydroisoquinoline stage and
the reaction did not proceed further to give 1-arylisoquinolines [24].
Heating a mixture of tryptamine with aldehyde in NMP at 140 °C for
Scheme 1. Pictet–Spengler reaction and aromatization.
24 h in oxygen atmosphere turned out to be the optimal condition to get
a good yield of β-carbolines (Table 1, entry 11). There was no reaction
when the reaction was conducted in Argon atmosphere in NMP at
Scheme 2. Domino Pictet-Spengler reaction and aromatization.
140 °C for 24 h (Table 1, entry 12) with strict exclusion to oxygen.This
application. Abramyants et al. [22a] had observed that an attempted
aromatization of tetrahydro-β-carboline-3-carboxylic acid led directly
to the β-carboline by a dehydrogenation and decarboxylation (Scheme
domino transformation exhibited good substrate scope with respect to
both the aldehyde (Table 2) and tryptamine (Table 3).
A number of aryl aldehydes (2b to 2l) (Table 2, entries 1–16),
hetero aryl aldehydes (2 m to 2p) (Table 2, entries 14–17) and aliphatic
aldehydes (2q and 2 r) (Table 2, entries 18–19) reacted smoothly with
tryptamines (1a and 1b) under these conditions to afford the respective
β-carbolines (Table 2, products 6b to 6 t) in good to excellent yield. No
significant substituent effect was observed. Aryladehydes bearing
electron-donating groups (Table 2, entries 2–6) afforded good yields
(75–82 %) of β-carbolines. In case of arylaldehydes substituted with
electron-withdrawing groups, the yields were even better (84–87 %) as
can be seen in Table 2, (entries 10–13). Overall, this domino transfor-
mation exhibited a good degree of functional group tolerance. Also, an
electron-donating substituent at 5th position of indole ring
(Table 2,entries 2, 4 and 10) did not have any major influence. Het-
eroaromatic aldehydes (2 m to 2p) were also found to be suitable
substrates for this transformation (Table 2, entries 14–17). Reaction of
furfural (2p) with tryptamine furnished the β–carboline 6 r possessing
the framework present in natural products, flazin and flazinamide
2
9
).by heating tetrahydro-β-carboline-3-carboxylic acid in DMSOat
5 °C.for 4–5 hr. It requires either the carboxylic acid or ester moiety at
the 3rd position, thus requiring additional steps and reactions as well as
lowering of atom economy. Furthermore, Dong et al. [22b] demon-
strated the aromatization of N-tosyl tetrahydro-β-carbolines in DMSO in
the presence of NaOH or DBU.Both the reports [22] involve two steps to
get the β-carbolines. Recently a biomemetic route was reported by
Wendlandt et al. [23] for 3,4-dihydro-β-carbolines but this route does
not proceed further to give aromatised β-carbolines. Against this
background, we report herein an efficient, atom economical and simple
route for a direct general one potsynthesis of β-carbolines involving a
domino Pictet-Spengler reaction and aromatization without the use of
any metal salt or acid catalyst by simply heating tryptamines with al-
dehydes in N-methyl-2-pyrolidone (NMP) at 140 °C.
2. Results and discussion
(
Fig. 1). Aliphatic aldehydes (2q and 2 r) were also smoothly converted
to the corresponding β-carbolines in good yields under these conditions
To begin with, we investigated the reaction of tryptamine (1a) with
-nitrobenzaldehyde (2a) in NMP without any acid or metal catalyst at
00 °C for 12 h. Under these conditions no reaction was observed
(
Table 2, entries 18–19).
4
1
When a reaction was carried out by treating tryptophan (1aa) with
87

S. Ramu, et al.
Molecular Catalysis 468 (2019) 86–93
Table 1
a
Optimization of reaction conditions .
o
4a:5a:6a Yield (%)d
Entry
Solvent
Temp. ( C)
Time (h)
1
2
3
4
5
6
7
8
9
NMP
NMP
NMP
DMF
DMSO
ClPh
Toluene
PEG 200
2
H O
DCE
100
120
130
130
130
130
111
130
100
83
12
12
24
24
24
24
24
24
24
24
24
24
12
NR
80 : - : -
< 5 : < 3:85
< 3: < 5:55
< 3: < 2:65
< 3: < 2:43
(70) 19 : - : -
˜10: < 2:20
20: - : -
e
f
10
11
12
13
NR
b
c
NMP
NMP
NMP
140
140
140
< 2: < 1:91
< 3: < 1: < 2
< 2: < 1:86
b
a
Reaction conditions: 1a (0.2 mmol), 2a (0.22 mmol), and Solvent (1 ml) in 5 ml RB flask.
Under oxygen atmosphere.
b
c
d
f
Under argon atmosphere.
e
1
Isolated yield; By H-NMR spectral analysis.
imine (3a), NR = No reaction.
Table 2
Substrate scope of the synthesis of β-carbolines .
carbolines using either Sulphur [25], selenium dioxide [26] or Pd/C
[27] as catalyst under harsh conditions. When tryptophan methyl ester
a
(
1ab) was treated with 2b under optimized conditions, the ester group
remained intact and the reaction gave rise to 7a in very good yield
Table 3, entry 2). The reaction was generalized using a number of
(
aromatic and heteroaromatic aldehydes. The results are presented in
Table 3. Yields were equally good with electron-rich (2d), as well as
electron-deficient (2 h) aromatic aldehydes and heteroaromatic alde-
hydes (2 m and 2n) (Table 3, entry 3–6).
Entry
R
1
R
2
Product (%)
Yield (%)b
Successful extension of this one pot domino methodology to typto-
phan methyl ester provides a suitable handle for further elaboration of
the β-carboline moiety and for preparing a number of β-carboline de-
rivatives and scaffolds for various screening studies [28]. Several
methods are there in the literature about aromatization of tetrahydro-β-
carbolines. These methods invariably employ either transition metal
catalysts [11–15]. or metal free reagents [16–21]. The disadvantages of
these methods are either the reaction conditions are harsh or the yields
are low or the reagents are toxic or they lack generalisation. Further, in
these methods, the reaction conditions for aromatization are quite
different from those of Pictet-Spengler reaction and hence this approach
requires preformed tetrahydro-β-carbolines.This is in remarkable con-
trast to the one pot green methodology developed by us, which does not
require preformed imine or tetrahydro-β-carboline. Further our pro-
tocol does not require the protection of indole nitrogen.
The failure to observe any reaction when oxygen was strictly ex-
cluded from the system by purging with nitrogen or argon (Table 1,
entry 12) clearly indicated the crucial role of oxygen in all the steps.
Also, the vast numbers of reports in literature on Pictet-Spengler reac-
tion reveal that the imine formation as well as the cyclisation requires
catalysis by an acid [6]. Since no external acid was used in this reaction,
the acid should have got generated in situ by the oxidation of the al-
dehyde under the reaction conditions, viz., in NMP at 140 °C and this in
situ generated acid should have catalysed the imine formation as well as
the cyclisation. This reasoning is supported by the finding that when
tryptamine 1a and aldehyde 2a were heated in argon atmosphere in
NMP at 140 °C in the presence of 10% p-nitrobenzoic acid, it afforded
the tetrahydro-β-carboline 4a in good yield (89%) as the sole product
1
2
3
4
5
6
7
Ph(2b)
Ph(2b)
H
6b
6c
6d
6e
6f
78
80
82
81
82
81
82
5-OCH
H
5-OCH
H
H
H
3
4-OMePh (2c)
4-OMePh (2c)
2-MePh (2d)
3
i
p- PrPh (2e)
6 g
6 h
(2f)
8
9
2-OH Ph (2 g)
4- OH Ph (2 h)
H
H
6i
75
76
88
89
84
89
81
6 j
6k
6 l
6 m
6n
6o
10
11
12
13
14
4-NO
2
Ph(2i)
5-OCH
3
4-ClPh (2 j)
2,4-diClPh (2k)
4-F Ph(2 l)
H
H
H
H
(
2 m)
2n)
2o)
2p)
15
16
17
H
H
H
6p
6q
6 r
82
81
78
(
(
(
1
1
8
9
n-Pr (2q)
Isopropyl (2 r)
H
H
6 s
6 t
81
79
a
Reaction conditions: 1a -1b (0.2 mmol), 2a-2 r (0.22 mmol), NMP (1.0 mL),
at 140 °C for 24 h in a 5 ml RB flask.
b
Isolated yields, under oxygen atmosphere.
2
b under optimized reaction conditions, it furnished directly the dec-
arboxylated aromatized product (6a) in good yield (71%) which was
reported in literature by the dehydrogenation of tetrahydro-β-
88

S. Ramu, et al.
Molecular Catalysis 468 (2019) 86–93
Table 3
a
Synthesis of various β-carboline methyl esters .
Entry
R
1
R
2
Product
Yield (%)b
1
2
3
4
5
Ph (2b)
Ph (2b)
4-OMePh (2d)
H (1aa)
6b
7a
7b
7c
7d
71
73
74
78
70
CH
3
CH
3
CH
3
CH
3
(1ab)
(1ab)
(1ab)
(1ab)
4-NO
2 m)
2n)
2
Ph (2 h)
(
6
CH
3
(1ab)
7e
71
(
a
1
Reaction conditions: 1aa -1ab (0.2 mmol), R CHO (0.22 mmol), NMP (1.0 mL), at 140 °C for 24 h in a 5 ml RB flask.
Isolated yields.
b
Table 4
Synthesis of various tetrahydro-β-carbolines .
proceeds without the need of any acid catalyst in the presence of
oxygen promoted by NMP.
a
3. Experimental Section
3.1. General methods
Yield (%)b
All reactions were carried out either under an argon or oxygen at-
Entry
R
1
Product
mosphere unless otherwise noted. All chemicals used in the reactions
aromatic aldehydes, aliphatic aldehydes and hetero aldehydes were
purchased from either Aldrich or Acros Organics and used without
further purification. CDCl and DMSO-d for NMR sample preparation
were purchased from Aldrich. Dry solvents such as NMP, DCE, DCM,
DMSO, ACN, Toluene and TFE used in synthesis with minimum purity
of 99.9% were purchased from Aldrich and Finar. Thin-layer chroma-
tography (TLC) was performed using 60 mesh silica gel plates visua-
1
2
3
4
5
6
4-NO
Ph(2b)
4- OH Ph (2 h)
4-ClPh (2 j)
4-F Ph(2 l)
2
Ph(2a)
4a
4b
4c
4d
4e
4f
89
87
83
92
92
87
(
3
6
(2o)
7
a
Isopropyl (2 r)
4 g
85
lized with short-wavelength UV light (254 nm). Silica gel 60 (230–400
1
Reaction conditions: 1a (0.2 mmol), R CHO (0.22 mmol), NMP (1.0 mL), at
mesh) was used for flash column chromatography. 1H NMR and
13
C
1
40 °C for 24 h in a 5 ml RB flask.
b
Isolated yields, 10 mol % acid, under argon atmosphere.
NMR spectra were recorded on a Bruker 500 instrument (500 MHz for
1
13
H and 125 MHz for C NMR). Data are reported as follows: Chemical
(
Table 4, entry 1). To
further demonstrate the effectiveness of the procedure, various al-
shift, multiplicity (s = singlet, d = doublet, t = triplet, q = quartet,
m = multiplet), Coupling constants, J, are reported in hertz.
1-(4-Nitrophenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole
[30] (4a)
dehydes (2b, 2 h, 2 j, 2 l, 2o and 2 r) were employed under same
conditions to obtain the products (Table 4, entries 2–6) in good yields.
These experiments clearly indicate thatthe crucial role of oxygenfor the
aromatization.
Hence, to understand the mechanism for the Pictet-Spengler and
aromatization, reaction of 1a with 2awas carried outin NMP in the
presence of oxygenunder optimized conditions (Table 1, entry 11) and
In an 5 ml RB flask with refluxing condensor were added a mixture
of 4-nitrobenzaldehyde (2a, 33 mg, 0.22 mmol, 1.1 equiv.,), tryptamine
(1a, 32 mg, 0.20 mmol, 1 equiv.,) and 4-nitrobenzoic acid (6.7 mg, 0.1
equiv.,) in NMP (1 ml) under argon atmosphere and the resulting
mixture was stirred at 140 °C for 24 h. After the reaction was complete,
the reaction mixture was concentrated under reduced pressure using
rotary evaporator. The crude product thus obtained was purified by
flash column chromatography on silica gel using mixture of hexane -
ethyl acetate (70:30) as eluent to obtain the product 4a Yellow solid:
1
monitoredby H NMR spectroscopy and TLC. It clearly revealedthe se-
quential formation and consumption of the imine 3a, tetrahydro-β-
carboline 4a, and dihydro-β-carboline 5a leading finally to 6a (Scheme
1
0b
6e
3
). The intermediacy of 3a
and 4a in this domino transformation
6f
1
was established by heating independently 3a [29] with catalytic
amount of p-nitrobenzoic acid and 4a without any acid catalystin NMP
at 140 °C in oxygen atmosphere for 24 h which afforded 6a. Heating 3a
alone in NMP at 140 °C did not lead to 6a. Moreover, in a separate
control experiment when the aldehyde 2a was heated in NMP at 140 °C
for a few hours, and the reaction mixture was analysed by NMR, it
confirmed the formation of p-nitro benzoic acid (2ab). It is thus clear
that formation of imineand cyclisation of imine requires an acid catalyst
which in our case was generated in situ and aromatisation of 3a
89% yield (52 mg, 0.178 mmol); mp: 170–172 °C (Lit : 172–173 °C); H
NMR (500 MHz, DMSO-d
6
) δ 10.53 (s, 1 H), 8.21 (d, J = 8.4 Hz, 2 H),
7.57 (d, J = 8.7 Hz, 2 H), 7.44 (d, J = 7.7 Hz, 1 H), 7.25 (dd, J = 8.0,
0.4 Hz, 1 H), 7.03 (t, J = 7.5 Hz, 1 H), 6.97 (t, J = 7.4 Hz, 1 H), 5.25 (s,
1 H), 3.01 (m, 2 H), 2.89 – 2.55 (m, 2 H).13C NMR (125 MHz, DMSO-
d ) δ 151.3, 147.2, 136.5, 134.5, 130.2, 127.2, 123.7, 121.3, 118.9,
6
118.2, 111.6, 109.1, 56.2, 41.4, 22.44.
1-Phenyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole [30] (4b)
This compound was prepared according to the general procedure
6f
4
a; White solid; 87% yield (43 mg); mp: 162–164 °C (Lit : 162–163 °C);
89

S. Ramu, et al.
Molecular Catalysis 468 (2019) 86–93
Scheme 3. Mechanism for the formation of β-carbolines(6).
1H NMR (500 MHz, DMSO- d
J = 7.8 Hz, 1 H), 7.49 (d, J = 11.2 Hz, 5 H), 7.40 (d, J = 8.0 Hz, 1 H),
) δ 11.08 (s, 1 H), 10.13 (s, 1 H), 7.59 (d,
2 H), 7.11 (t, J = 7.5 Hz, 1 H), 7.06 (t, J = 7.4 Hz, 1 H), 5.26 (s, 1 H),
3.31 – 2.97 (m, 2 H), 2.81 (m, 2 H).13C NMR (125 MHz, DMSO-d
) δ
6
6
7
3
.19 (t, J = 7.4 Hz, 1 H), 7.11 (t, J = 7.3 Hz, 1 H), 6.03 (s, 1 H), 3.60 –
.41 (m, 2 H), 3.18 (s, 1 H), 3.09 (s, 1 H). C NMR (125 MHz, DMSO-
150.3, 149.0, 138.7, 136.6, 136.5, 134.6, 127.3, 123.9, 121.3, 118.9,
118.2, 111.7, 109.2, 54.8, 41.7, 22.44.
1
3
d
1
6
) δ 137.2, 135.3, 130.4, 130.2, 129.3, 129.0, 126.2, 122.5, 119.6,
1-Isopropyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole
(4g)
This compound was prepared according to the general procedure
[6f]
18.7, 112.1, 107.9, 56.06, 40.5, 18.7.
4-(2,3,4,9-Tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenol (4c)
6
f
This compound was prepared according to the general procedure
4a; Yellow 1solid; 85% yield (36 mg); mp: 117–119 °C (Lit :
1
4
a; Yellow solid; 83% yield (43 mg); mp: 189–195 °C. H NMR
117–118 °C); H NMR (500 MHz, DMSO-d
6
) δ 10.62 (s, 1 H), 7.37 (d,
(
500 MHz, DMSO- d
6
) δ 10.62 (s, 1 H), 7.57 (d, J = 7.7 Hz, 1 H), 7.45
J = 7.7 Hz, 1 H), 7.31 (d, J = 8.0 Hz, 1 H), 7.03 (t, J = 7.5 Hz, 1 H),
6.95 (t, J = 7.4 Hz, 1 H), 3.90 (d, J = 1.4 Hz, 1 H), 3.36 – 2.99 (m, 1 H),
2.96 – 2.73 (m, 1 H), 2.75 – 2.41 (m, 1 H), 2.34 (m, 1 H), 1.10 (d,
(
d, J = 8.5 Hz, 2 H), 7.40 (t, J = 7.4 Hz, 3 H), 7.21 – 7.14 (m, 1 H), 7.11
(
t, J = 7.4 Hz, 1 H), 5.21 (s, 1 H), 3.34 – 3.13 (m, 2 H), 3.11 – 3.00 (m,
1
3
13
1
1
1
H), 2.96 – 2.74 (m, 2 H). C NMR (125 MHz, DMSO- d
6
) δ 159.1,
J = 6.9 Hz, 3 H), 0.76 (d, J = 6.8 Hz, 3 H); C NMR (125 MHz, DMSO-
36.9, 131.5, 130.2, 126.4, 126.1, 122.2, 119.4, 118.5, 116.0, 111.9,
07.81, 55.9, 40.5, 19.06. HRMS (ESI): calcd. for C17
d ) δ 137.1, 136.3, 127.6, 120.6, 118.5, 117.7, 111.3, 108.7, 57.8, 43.2,
6
+
H
17
N
2
O
[M
31.2, 22.9, 20.1, 17.0.
+
+
H] :265.1341; found: 265.1339.
-(4-Chlorophenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole
30] (4d)
This compound was prepared according to the general procedure
1
[
3.2. 1-(4-Nitrophenyl)-9H-pyrido[3,4-b]indole [20] (6a)
6f
4
2
a; Yellow solid; 92% yield (51 mg); mp: 205–207 °C (Lit :
In an 5 ml RB flask with refluxing condensor were added a mixture
of 4-nitrobenzaldehyde (2a, 33 mg, 0.22 mmol, 1.1 equiv.,), tryptamine
(1a, 32 mg, 0.20 mmol, 1 equiv.,) in NMP (1 ml) under oxygen atmo-
sphere and the resulting mixture was stirred at 140 °C for 24 h. After the
reaction was complete, the reaction mixture was concentrated under
reduced pressure using rotary evaporator. The crude product thus ob-
tained was purified by flash column chromatography on silica gel using
mixture of hexane–ethyl acetate (70:30) as eluent to obtain the product
6a as Yellow solid; 91% yield (53.3 mg, 0.182 mmol); mp:244-246 °C
1
6
06–207 °C); H NMR (500 MHz, DMSO- d ) δ 10.53 (s, 1 H), 7.49 (d,
J = 7.7 Hz, 1 H), 7.36 (dd, J = 8.5, 5.7 Hz, 2 H), 7.32 (d, J = 7.9 Hz,
1
1
2
1
1
H), 7.17 (t, J = 8.8 Hz, 2 H), 7.12 – 7.05 (m, 1 H), 7.02 (t, J = 7.4 Hz,
H), 5.15 (s, 1 H), 3.17 – 3.06 (m, 1 H), 3.04 – 2.93 (m, 1 H), 2.87 –
1
3
.76 (m, 1 H), 2.77 – 2.68 (m, 1 H). C NMR (125 MHz, DMSO- d ) δ
6
42.5, 136.7, 135.3, 132.6, 130.9, 128.6, 127.5, 121.3, 118.9, 118.2,
11.7, 109.1, 56.6, 41.8, 22.7.
1
-(4-Fluorophenyl)-2,3,4,9-tetrahydro-1H-pyrido [3,4b] indole
30] (4e)
This compound was prepared according to the general procedure
a; Yellow solid; 92% yield (48 mg); mp: 138–142 °C (Lit.[39]:
(Lit.20: 243–246 °C);. H NMR H NMR (500 MHz, DMSO–d
1
1
) δ 11.71 (s,
[
6
1 H), 8.51 (d, J = 4.9 Hz, 1 H), 8.42 (d, J = 7.8 Hz, 2 H), 8.29 (dd,
J = 13.7, 8.1 Hz, 3 H), 8.20 (d, J = 4.7 Hz, 1 H), 7.67 (d, J = 8.1 Hz,
1 H), 7.58 (t, J = 7.5 Hz, 1 H), 7.28 (t, J = 7.3 Hz, 1 H). C NMR
4
1
13
1
39–140 °C); H NMR (500 MHz, DMSO-d
6
) δ 10.88 (s, 1 H), 7.53 (d,
J = 7.4 Hz, 1 H), 7.34 (d, J = 7.3 Hz, 1 H), 7.21 (d, J = 7.5 Hz, 2 H),
6
(125 MHz, DMSO−d ) δ: 147.6, 145.1, 141.7, 139.9, 139.2, 133.9,
130.4, 130.1, 129.1, 124.3, 122.2, 121.2, 120.3, 115.6, 112.9.
1-Phenyl-9H-pyrido[3,4-b]indole [20] (6b)
7
2
2
1
4
.12 (d, J = 7.1 Hz, 1 H), 7.06 (t, J = 6.5 Hz, 1 H), 6.89 (d, J = 7.5 Hz,
H), 5.77 (s, 2 H), 3.53 – 3.29 (m, 2 H), 3.04 (dd, J = 54.7, 15.7 Hz,
1
3
H). C NMR (125 MHz, DMSO-d
6
) δ 162.9, 161.1, 139.8, 136.6,
This compound was prepared according to the general procedure
2
0
35.7, 130.9, 127.4, 121.1, 118.8, 118.1, 115.3, 111.6, 108.9, 56.4,
1.8, 22.7.
6a. Yellow 1solid; 78% yield (38 mg); mp: 241–243 °C (Lit.
:
2
41–244 °C); H NMR (500 MHz, DMSO−d
6
) δ: 11.57 (s, 1 H), 8.48 (d,
= 5.3 Hz, 1 H), 8.27 (d, J = 7.7 Hz, 1), 8.12-8.04 (m, 3H),
1
-(Pyridin-3-yl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole
31] (4f)
This compound was prepared according to the general procedure
J
13
[
7.68 − 7.50 (m, 5 H), 7.28 (t, J = 8 Hz, 1 H); C NMR (125 MHz,
DMSO−d
6
) δ: 142.7, 141.6, 138.9, 138.8, 133.5, 129.7, 129.2, 128.9,
1
4
a; White solid; yield (43 mg); mp: 138–142 °C. H NMR (500 MHz,
) δ 10.69 (s, 1 H), 8.64 (s, 1 H), 8.54 (d, J = 4.5 Hz, 1 H), 7.67
d, J = 7.9 Hz, 1 H), 7.52 (d, J = 7.7 Hz, 1 H), 7.35 (dd, J = 7.6, 4.4 Hz,
128.7, 122.1, 121.4, 120.0, 114.4, 113.0.
DMSO-d
(
6
6-Methoxy-1-phenyl-9H-pyrido[3,4-b]indole [31] (6c)
This compound was prepared according to the general procedure
3
7
6
a; Yellow solid; 80% yield (43 mg); mp: 190–195 °C (Lit. :
90

S. Ramu, et al.
Molecular Catalysis 468 (2019) 86–93
1
93–196 °C); 1H NMR (500 MHz, DMSO−d
J = 4.5 Hz, 1 H), 8.09 (m, 3 H), 7.82 (s, 1 H), 7.62 (m, 3 H), 7.5 (t,
6
) δ:11.42 (s, 1 H), 8.45 (d,
291 − 294 °C). 1H NMR (500 MHz, DMSO−d
6
) δ: 11.42 (s, 1 H), 8.41
(d, J = 5.5 Hz, 1 H), 8.24 (d, J = 8.0 Hz, 1 H), 8.03 (d, J = 5.0 Hz, 1 H),
8.92 (m, 2 H), 7.67 (d, J = 8 Hz, 1 H), 7.56 (t, J = 7 Hz, 1 H), 7.26 (d,
1
3
J = 7.5 Hz, 1 H), 7.25 (d, J = 9 Hz, 1 H), 3.88 (s, 3 H); C NMR
125 MHz, DMSO−d
(
1
6
) δ: 154.0, 142.7, 138.9, 136.5, 134.1, 129.6,
29.2,128.9, 128.8, 128.7, 121.7, 118.8, 114.4, 113.8, 103.7, 56.1.
-(4-Methoxyphenyl)-9H-pyrido[3,4-b]indole [19] (6d)
J = 7.5 Hz, 1 H), 7.02 (m, 2 H); 13C NMR (75 MHz, DMSO−d
158.4, 143.1, 141.5, 138.7, 133.1, 130.2, 129.8, 129.4, 128.4, 121.9,
121.4, 119.8, 116.1, 113.5, 112.9.
6
) δ:
1
This compound was prepared according to the general procedure
6-Methoxy-1-(4-nitrophenyl)-9H-pyrido[3,4-b]indole (6k)
This compound was prepared according to the general procedure
6
1
1
a; Yellow solid; 82% yield (44 mg); mp: 155–159 °C (Lit.19
:
1
1
56–159 °C); H NMR (500 MHz, DMSO−d
6
) δ: 11.67 (s, 1 H), 8.52 (s,
H), 8.22 (d, 1 H), 8.13 (d, J = 7.9 Hz, 2 H), 8.02 (s, 1 H), 7.81 (t,
6a; Yellow solid; 88% yield (56 mg); mp:197-204 °C.
(500 MHz, DMSO−d
H NMR
6
) δ:11.56 (s, 1 H), 8.49 (d, J = 5.0 Hz, 1 H), 8.44
(d, J = 9 Hz, 1 H), 8.31 (d, J = 9 Hz, 1 H), 8.21 (d, J = 5.5 Hz,1 H),
7.84 (d, J = 2 Hz, 1 H), 7.58 (d, J = 8 Hz, 1 H), 7.25 (d, J = 8 Hz, 1 H),
) δ: 154.2, 147.5, 145.1,
139.9, 138.6, 136.5, 134.4,130.3, 129.9, 124.3, 121.5, 119.2, 115.7,
J = 7.1 Hz, 1 H), 7.61 (t, J = 8.1 Hz, 1 H), 7.29 (t, J = 7.0 Hz, 1 H),
1
3
7
6
.18 (d, J = 8.7 Hz, 2 H), 3.83 (s, 3 H); C NMR (125 MHz, DMSO−d )
δ: 160.1, 142.8, 141.7, 138.8, 133.4, 131.5, 130.3, 129.7, 121.9, 121.5,
19.9, 114.6, 113.8, 112.9, 55.7.
3.88(s, 3 H); 13C NMR (125 MHz, DMSO−d
6
1
+
6-Methoxy-1-(4-methoxyphenyl)-9H-pyrido[3,4-b]indole (6e)
113.7, 103.9, 56.1. HRMS (ESI): calcd. for
+H] :320.1035; found: 320.1034.
C
18
H
14
N
3
O
3
[M
+
This compound was prepared according to the general procedure
1
6
(
(
7
6
1
1
a; Yellow solid; 81% yield (49 mg); mp: 190–195 °C. H NMR
1-(4-Chlorophenyl)-9H-pyrido[3,4-b]indole [20] (6l)
This compound was prepared according to the general procedure
500 MHz, DMSO−d
d, J = 5 Hz, 1 H), 7.99 (d, J = 7 Hz, 2 H), 7.79 (d, J = 2.5 Hz,1 H),
6
) δ:11.30 (s, 1 H), 8.38 (d, J = 5.5 Hz, 1 H), 8.05
2
0
6a; Light yellow solid; Yield:89% (49 mg); mp: 220 − 260 °C (Lit.
200 − 265 °C); 1H NMR (500 MHz, CDCl
) δ:8.97 (s, 1 H), 8.43 (d,
J = 5.0 Hz, 1 H), 8.06 (d, J = 8 Hz, 1 H), 7.84 (d, J = 5.5 Hz, 1 H), 7.73
:
.57 (d, J = 9 Hz, 1 H), 7.21 (m, 1 H), 7.15 (d, J = 7 Hz, 1 H), 3.87(s,
3
1
3
H); C NMR (125 MHz, DMSO−d
6
) δ: 160.0, 153.9, 142.6, 138.1,
1
3
38.0, 136.4, 133.7,131.3, 128.7, 129.4, 121.6, 118.6, 114.6, 113.8,
(m, 2 H), 7.46 (m, 1 H), 7.38 (m, 1 H), 7.36(m, 2 H), 7.20 (m, 1 H);
C
+
03.7, 55.9, 55.7. HRMS (ESI): calcd. for
C
19
H
17
2
N O
2
[M
NMR (125 MHz, CDCl ) δ 142.0, 140.9, 139.4, 136.9, 134.9, 133.7,
3
+
+
H] :305.1290; found: 305.1287.
-(o-Tolyl)-9H-pyrido[3,4-b]indole [34] (6f)
This compound was prepared according to the general procedure
130.4, 129.6, 129.5, 129.3, 128.8, 121.9, 120.5, 114.3, 111.9.
1-(2,4-Dichlorophenyl)-9H-pyrido[3,4-b]indole (6m)
1
This compound was prepared according to the general procedure
1
1
6
a; Yellow solid; 82% yield (42 mg); mp: 192–196 °C H NMR
6a; Yellow solid; 84% yield (52 mg); mp: 245–280 °C; H NMR
(
500 MHz, DMSO−d
6
) δ:11.41 (s, 1 H), 8.52 (s, 1 H), 8.28 (d, J = 8 Hz,
6
(500 MHz, DMSO−d ) δ:11.67 (s, 1 H), 8.44 (d, J = 5.0 Hz, 1 H), 8.26
1
3
d
1
2
H), 8.12 (s, 1 H), 7.73 (d, J = 8.5 Hz, 1 H), 7.59 (m, 2 H), 7.41 (m,
(s, 1 H), 8.16 (m, 2 H), 7.98 (m, 1 H), 7.82 (d, J = 8.3 Hz, 1 H), 7.66 (m,
H), 7.28 (t, J = 7.5 Hz, 1 H), 2.29 (s, 3 H); 1 C NMR (125 MHz, DMSO-
3
1 H), 7.57(t, J = 7.3 Hz, 1 H), 7.27 (t, J = 7.2 Hz, 1 H); C NMR
13
6
) δ 144.8, 141.9, 138.8, 138.7, 137.2, 134.89, 131.4, 130.6, 129.2,
29.1, 128.9, 126.7, 122.5, 122.4, 121.9, 120.2, 114.6, 114.4, 113.2,
0.41.
(100 MHz, DMSO−d
131.7, 131.4, 130.5, 130.2, 129.0, 128.9, 122.2, 121.1, 120.3, 115.2,
112.8. HRMS (ESI): calcd. for C17H11Cl
found: 313.0297.
6
) δ: 141.6, 139.8, 139.1, 138.9, 133.5, 132.1,
+
+
2
N
2
[M+H] :313.0299;
1-(4-Isopropylphenyl)-9H-pyrido[3,4-b]indole (6g)
This compound was prepared according to the general procedure
a; Yellow solid; 81% yield (46 mg); mp: 183–188 °C. H NMR
1-(4-Fluorophenyl)-9H-pyrido[3,4-b]indole [20] (6n)
This compound was prepared according to the general procedure
1
6
(
500 MHz, DMSO−d
J = 8 Hz, 1 H), 8.20 (d, J = 8.5 Hz, 2 H), 8.12 (d, J = 5 Hz, 1 H), 7.93
d, J = 8 Hz, 1 H), 7.69 (t, J = 8 Hz, 1 H), 7.48 (d, J = 8.5 Hz, 2 H),
.36 (t, J = 7.5 Hz, 1 H), 2.95 (m, 1 H), 1.30 (d, J = 7 Hz, 6 H); 13
NMR (125 MHz, DMSO−d ) δ: 149.2, 146.4, 143.3, 141.6, 139.3,
35.8, 135.0, 133.6, 133.5, 133.3,126.9, 126.8, 126.3, 119.0, 118.8,
6
) δ:11.82 (s, 1 H), 8.65 (d, J = 5 Hz, 1 H), 8.32 (d,
6a; White solid: 89% yield (46 mg); mp: 207–209 °C
(Lit.20:206–209 °C); H NMR (500 MHz, DMSO-d
1
6
) δ 11.60 (s, 1 H), 8.47
(
7
(d, J = 3.7 Hz, 1 H), 8.23 (d, J = 7.6 Hz, 1 H), 8.12 (s, 2 H), 8.08 (s,
1 H), 7.70 (d, J = 7.1 Hz, 1 H), 7.57 (t, J = 7.4 Hz, 1 H), 7.43 (t,
C
J = 8.3 Hz, 2 H), 7.26 (t, J = 7.1 Hz, 1 H);13
DMSO−d
6
C
NMR (125 MHz,
) δ: 163.8, 161.9, 141.7, 138.8, 135.4, 133.5, 131.1, 129.8,
128.7, 122.0, 121.4, 120.0, 116.1, 114.3, 112.9.
6
1
1
+
+
17.6, 24.8. HRMS (ESI): calcd. for C20
H
19
N
2
[M+H] :287.1548;
found: 287.1545.
-(Naphthalen-1-yl)-9H-pyrido[3,4-b]indole [32] (6h)
This compound was prepared according to the general procedure
1-(Thiophen-2-yl)-9H-pyrido[3,4-b]indole [32] (6o)
1
This compound was prepared according to the general procedure
6a; Yellow solid; 81% yield (40 mg); mp: 164–166 °C (Lit.[38]:165-
19
166 °C); 1H NMR (500 MHz, DMSO−d
J = 5.0 Hz, 1 H), 7.70 (m, 2 H), 7.55 (d, J = 5.0 Hz, 1 H), 7.38 (d,
J = 8.0 Hz, 1 H), 7.24 (d, J = 5 Hz, 1 H), 7.15 (t, J = 7.5 Hz, 1 H),
6.89(t, J = 3.5 Hz, 1 H), 6.81 (t, J = 9 Hz, 1 H); 13C NMR (125 MHz,
6
1
1
7
7
a; Off white solid; 82% yield (48 mg); mp: 179–182 °C; (Lit.
:
6
) δ:11.15 (s, 1 H), 7.97 (d,
1
78–180 °C); H NMR (500 MHz, DMSO−d
6
) δ:11.43 (s, 1 H), 8.69 (s,
H), 8.38 (d, J = 8 Hz, 1 H), 8.27 (d, J = 5.5 Hz, 2 H), 8.12 (m, 1 H),
.47 (m, 2 H), 7.92 (t, J = 7.5 Hz 2 H), 7.74 (m, 1 H), 7.63 (m, 1 H),
.58 (m, 1 H), 7.48 (d, J = 8 Hz, 1 H), 7.35(t, J = 8 Hz, 1 H); 13C NMR
DMSO−d ) δ: 144.3, 141.8, 138.6, 137.2, 131.5, 130.3, 128.9, 128.9,
6
(
1
1
125 MHz, DMSO−d
31.9, 129.3, 128.8, 128.7, 128.2, 126.9, 126.6, 126.3, 126.2, 122.3,
21.6, 120.0, 114.6, 112.9.
6
) δ: 143.4, 141.7, 138.6, 136.3, 135.4, 134.3,
128.4, 126.3, 122.0, 121.4, 120.4, 114.3, 113.1.
1-(Pyridin-2-yl)-9H-pyrido[3,4-b]indole [33] (6p)
This compound was prepared according to the general procedure
2
2a
2-(9H-Pyrido[3,4-b]indol-1-yl)phenol [21] (6i)
6a; Yellow 1solid; 82% yield (40 mg); mp: 171–175 °C. (Lit.
:
This compound was prepared according to the general procedure
173–175 °C). H NMR (500 MHz, DMSO−d ) δ:11.98 (s, 1 H), 8.90 (d,
6
6
a; Yellow solid; 75% yield (38 mg); mp: 200–204 °C (Lit.2
2a
:
J = 4.5 Hz, 1 H), 8.64 (d, J = 8 Hz, 1 H), 8.49 (d, J = 5.0 Hz, 1 H), 8.28
(d, J = 8.0 Hz, 1 H), 8.22 (d, J = 5 Hz, 1 H), 8.03 (t, J = 6 Hz, 1 H),
7.89(d, J = 8 Hz, 1 H), 7.59 (t, J = 8 Hz, 1 H),7.52(t, J = 4.5 Hz, 1 H),
1
200–202 °C). H NMR (500 MHz, DMSO−d
6
) δ: 13.61 (bs, 1 H),11.70
(
s, 1 H), 8.44 (d, J = 3 Hz, 1 H), 8.26 (s, 1 H), 8.15 (s, 2 H), 7.78 (d,
J = 8 Hz, 1 H), 7.62 (t, J = 7.5 Hz, 1 H), 7.42 (t, J = 8.25 Hz, 1 H), 7.28
t, J = 7.5 Hz, 1 H), 7.10 (t, J = 8.5 Hz, 2 H); 13C NMR (125 MHz,
DMSO−d
7.29 (t, J = 7.5 Hz, 1 H); 13C NMR (125 MHz, DMSO−d
) δ: 157.5,
6
(
149.2, 141.5, 138.6, 138.2, 137.7, 137.7,134.0, 130.4, 128.9, 123.8,
121.3, 120.8, 120.1, 116.1, 113.4.
6
) δ: 158.5, 142.4, 141.9, 136.0, 132.7, 130.9, 130.6, 129.4,
29.1, 122.0, 121.2, 120.4, 119.4, 117.9, 114.5, 113.1.
-(9H-Pyrido[3,4-b]indol-1-yl)phenol [37] (6j)
This compound was prepared according to the general procedure
a; Yellow solid; 76% yield (39 mg); mp: 292 − 294 °C (Lit.37
1
1-(pyridin-3-yl)-9H-pyrido[3,4-b]indole [19] (6q)
This compound was prepared according to the general procedure
4
1
9
6a; White solid; 81% yield (39 mg); mp: 205–208 °C(Lit.
:
1
6
:
6
205–208 °C). H NMR (500 MHz, DMSO-d ) δ 9.12 (d, J = 1.9 Hz, 1 H),
91

S. Ramu, et al.
Molecular Catalysis 468 (2019) 86–93
8
.66 (dd, J = 4.8, 1.5 Hz, 1 H), 8.44 (d, J = 5.2 Hz, 1 H), 8.34 (dd,
J = 7.9, 1.9 Hz, 1 H), 8.24 (d, J = 7.9 Hz, 1 H), 8.14 (d, J = 5.2 Hz,
H), 7.64 – 7.59 (m, 2 H), 7.55 (dd, J = 11.2, 4.0 Hz, 1 H), 7.26 (t,
1H NMR (500 MHz, DMSO−d
6
) δ: 11.76 (s, 1 H), 8.79 (s, 1 H), 8.38 (d,
J = 5 Hz, 1 H), 7.80 (d, J = 5 Hz, 2 H), 7.72 (d, J = 10 Hz, 1 H), 7.58 (s,
1
1 H), 7.32 (m, 1 H), 6.82 (m, 2 H), 3.93 (s, 3 H); 13C NMR (125 MHz,
1
3
J = 7.1 Hz, 1 H); C NMR (125 MHz, DMSO-d
6
) δ 149.7, 149.2, 141.5,
39.6, 139.1, 136.5, 134.3, 133.6, 129.9, 129.1, 124.6, 122.2, 121.0,
20.4, 115.1, 112.7.
-(Furan-2-yl)-9H-pyrido[3,4-b]indole [36] (6r)
6
DMSO-d ) δ 167.1, 150.7, 143.9, 142.1, 137.3, 134.9, 130.4, 130.3,
129.4, 125.6, 122.6, 122.1, 121.1, 120.9, 116.4, 115.9, 114.7, 114.5,
113.6, 52.8.
1
1
1
Methyl
1-(thiophen-2-yl)-9H-pyrido[3,4-b]indole-3-carbox-
This compound was prepared according to the general procedure
ylate [35] (7d)
6
1
a; Yellow solid; 78% yield (36 mg); mp: 167–168 °C(Lit.36
:
This compound was prepared according to the general procedure
1
35
1
67–168 °C) H NMR (500 MHz, DMSO−d
6
) δ:11.5 (s, 1 H), 8.39 (d,
J = 5.0 Hz, 1 H), 8.24 (d, J = 7.5 Hz, 1 H), 8.06 (d, J = 5.0 Hz, 1 H),
7a; Yellow solid; 70% yield (42 mg); mp: 190–196 °C (Lit. : 195 °C); H
NMR (400 MHz, DMSO−d ) δ: 11.8 (s, 1 H), 8.83 (s, 1 H), 8.36 (d,
J = 7.9 Hz, 1 H), 8.14 (d, J = 3.7 Hz, 1 H), 7.78 (m, 2 H), 7.61 (t,
6
7
2
1
1
.98 (s, 1 H), 7.79 (d, J = 8.5 Hz, 1 H), 7.58 (t, J = 7 Hz, 1 H), 7.28(m,
1
3
13
H), 6.78 (m, 1 H); C NMR (125 MHz, DMSO−d
6
) δ: 153.7, 144.2,
J = 7.1 Hz,1 H), 7.33(m, 2 H), 3.95 (s, 3 H);
C NMR (100 MHz,
) δ: 166.1, 142.9, 142.0, 136.8, 136.7, 132.9,130.2, 135.3,
41.6, 138.5, 133.6, 131.1, 129.9, 128.8, 122.0, 120.9, 120.1, 114.3,
13.1, 112.7, 109.3.
DMSO−d
6
129.3, 129.2, 128.9, 127.1,122.3, 121.5, 121.1,116.9, 113.4, 52.6.
Methyl 1-(pyridin-2-yl)-9H-pyrido[3,4-b]indole-3-carboxylate
[22] (7e)
1-Propyl-9H-pyrido[3,4-b]indole [31] (6s)
This compound was prepared according to the general procedure
2
0
6
1
a; Brown colour solid; 81% yield (34 mg); mp: 170–172 °C (Lit.
:
This compound was prepared according to the general procedure
1
22a
70–175 °C). H NMR (500 MHz, DMSO-d
6
) δ 11.55 (s, 1 H), 8.25 (d,
7a; Yellow 1solid; 71% yield (42 mg); mp: 178–181 °C (Lit.
:
J = 5.3 Hz, 1 H), 8.18 (d, J = 7.8 Hz, 1 H), 7.91 (d, J = 5.3 Hz, 1 H),
.61 (d, J = 8.2 Hz, 1 H), 7.54 (dd, J = 7.1, 1.1 Hz, 1 H), 7.22 (dd,
J = 11.0, 3.9 Hz, 1 H), 3.15 – 3.00 (m, 2 H), 1.86 (m, 2 H), 1.00 (t,
181–182 °C) H NMR (400 MHz, DMSO−d ) δ: 12.3 (s, 1 H), 8.98 (s,
6
7
1 H), 8.90 (d, J = 4.0 Hz, 1 H), 8.66 (d, J = 7.9 Hz, 1 H), 8.42 (d,
J = 7.8 Hz, 1 H), 8.06 (t, J = 7.1 Hz,1 H), 7.94 (d, J = 8.2 Hz, 1 H),
7.62 (t, J = 7.6 Hz,1 H),7.54 (m,1 H), 7.32 (t, J = 7.4 Hz,1 H), 3.97 (s,
1
3
J = 7.4 Hz, 3 H); C NMR (125 MHz, DMSO−d
6
) δ: 146.3, 138.0,
34.6, 128.2, 127.6, 122.1, 121.5, 119.6, 113.0, 112.4, 35.9, 21.9,
4.4.
1
1
3 H); 13C NMR (100 MHz, DMSO−d
6
) δ: 166.3, 156.7, 149.2, 141.9,
138.1, 137.8,136.3, 135.3, 130.5, 129.3, 124.3, 122.4,121.6, 121.2,
120.9,118.4, 113.8, 52.6.
1-Isopropyl-9H-pyrido[3,4-b]indole [31] (6t)
This compound was prepared according to the general procedure
a; White solid; 79% yield (33 mg); mp: 225–229 °C (Lit.2
2b
:
4. Conclusion
6
2
1
1
29–230 °C). H NMR (500 MHz, DMSO−d
6
) δ: 8.23 (d, J = 5.3 Hz,
H), 8.12 (d, J = 7.9 Hz, 1 H), 7.87 (d, J = 5.3 Hz, 1 H), 7.60 (d,
In summary, we have developed a simple, efficient and atom eco-
nomical flexible green methodology for the one pot synthesis of β-
carbolines directly from tryptamine and aldehydes involving a domino
Pictet-Spengler cyclization and aromatization. By switching the reac-
tion conditions, we can get the products of our choice either tetrahydro-
β-carbolines or β-carbolines.
J = 8.2 Hz, 1 H), 7.50 (dd, J = 11.3, 4.0 Hz, 1 H), 7.18 (t, J = 7.4 Hz,
1
3
1
H), 3.62 (m, 1 H) 1.35 (d, J = 6.9 Hz, 6 H); C NMR (125 MHz,
DMSO-d ) δ 150.8, 140.6, 137.8, 133.3, 128.3, 127.8, 121.9, 121.4,
19.7, 113.1, 112.3, 31.3, 21.8.
6
1
3.3. Methyl 1-phenyl-9H-pyrido [3, 4-b] indole-3-carboxylate [19] (7a)
Acknowledgements
In a 5 ml RB flask were added a mixture of benzaldehyde (2b) (23
μl, 0.22 mmol, 1.2 equiv.,), Tryptophan methyl ester (1ab) (44 mg,
Dr B.B. thanks Department of Science and Technology - SERB Young
Scientist Project, Government of India for financial support (SB/FT/CS-
082/2014) to carry out this work. S.R. thanks DST-SERB for Junior
Research Fellowship (JRF) and S.S. thanks SRM Institute of Science and
Technology for Junior Research Fellowship (JRF) and CSIR-SRF 09/
1045(0024)2K18 EMR-I. Dr B.B. thanks IIISM, SRM Institute of Science
and Technology for providing NMR, HPLC and LCMS facilities. We
acknowledge DST-FIST (fund for improvement of S&T infrastructure)
for financial assistance for Department of Chemistry, SRM Institute of
0
.20 mmol, 1 equiv.) in NMP (1 ml) and the resulting mixture was he-
ated at 140 °C under oxygen atmosphere for 24 h. After the reaction was
complete, the reaction mixture was concentrated under reduced pres-
sure using rotary evaporator. The crude product thus obtained was
purified by flash column chromatography on silica gel using mixture of
hexane–ethyl acetate (70:30) as eluent to obtain the product 7a as
1
9
white solid in 73% yield (44 mg, 0.146 mmol); mp: 257–259 °C (Lit.
:
1
2
1
7
57–259 °C). HNMR (500 MHz, DMSO−d
H), 8.44 (d, J = 10 Hz,1 H), 8.07 (d, J = 10 Hz, 2 H), 7.75 (m, 1 H),
6
) δ: 11.97 (s, 1 H), 8.95 (s,
Science
&
Technology, Kattankulathur (No.SR/FST/CST-266/
1
3
13
.68 (m, 2 H),7.58 (m, 2 H), 7.33 (m, 1 H), 3.97 (s, 3 H); C NMR
) δ 166.9, 142.9, 142.3, 138.4, 137.5, 135.4,
30.0, 129.8, 129.6, 129.52, 129.5, 129.4, 122.8, 122.7, 121.9, 121.2,
17.6, 117.4, 113.7, 52.9.
Methyl 1-(4-methoxyphenyl)-9H-pyrido[3,4-b]indole-3-car-
C
2015(c)).Prof. K.K.B. thanks the Indian National Science Academy for
the INSA Senior Scientist position.
NMR (125 MHz, DMSO-d
6
1
1
Appendix A. Supplementary data
boxylate [19] (7b)
Supplementary material related to this article can be found, in the
online version, at doi:https://doi.org/10.1016/j.mcat.2019.02.018.
This compound was prepared according to the general procedure
7
a; White solid; 74% yield (48 mg); mp: 226–229 °C (Lit.19:228-231 °C).
1
H NMR (500 MHz, DMSO−d
6
)δ:11.39 (s, 1 H), 8.88 (s, 1 H), 8.41 (d,
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