Metal-free propargylation/aza-annulation approach to substituted β-carbolines and evaluation of their photophysical properties

Article abstract of DOI:10.1039/c9ob01959f

An efficient acid-catalyzed propargylation/aza-annulation sequence was developed under metal-free reaction conditions, thus leading to a one-pot synthesis of a variety of substituted β-carbolines starting from propargylic alcohols and indole 2-carbonyls. This versatile strategy was further extended to the synthesis of 5-azaindoles and 5-azabenzothiazoles. Optical properties suggested that manipulation of electron donor and acceptor moieties on β-carbolines has an impact on their ground and excited state electronic behavior. This leads to blue or green emission and should facilitate the development of organic light emitting diodes (OLEDs). Electrochemical and stability studies revealed that 4a-6 shows ease of redox activity and photostability during illumination.

Full text of DOI:10.1039/c9ob01959f

Organic &
Biomolecular Chemistry
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Metal-free propargylation/aza-annulation
approach to substituted β-carbolines and
evaluation of their photophysical properties†‡
Cite this: Org. Biomol. Chem., 2019,
7, 9291
1
a,b
a,b
a,b
b,c
Chada Raji Reddy,
Lingamallu Giribabu,
*
Mounika Aila, Puppala Sathish, Madoori Mrinalini,
b,c
b,c
d
Seelam Prasanthkumar
and René Grée
An efficient acid-catalyzed propargylation/aza-annulation sequence was developed under metal-free
reaction conditions, thus leading to a one-pot synthesis of a variety of substituted β-carbolines starting
from propargylic alcohols and indole 2-carbonyls. This versatile strategy was further extended to the syn-
thesis of 5-azaindoles and 5-azabenzothiazoles. Optical properties suggested that manipulation of elec-
tron donor and acceptor moieties on β-carbolines has an impact on their ground and excited state elec-
tronic behavior. This leads to blue or green emission and should facilitate the development of organic
light emitting diodes (OLEDs). Electrochemical and stability studies revealed that 4a-6 shows ease of
redox activity and photostability during illumination.
Received 6th September 2019,
Accepted 8th October 2019
DOI: 10.1039/c9ob01959f
rsc.li/obc
of organic light-emitting diodes (OLEDs). In addition,
β-carbolines with weak electron donating nature can be
Introduction
Aza-heterocycles are an important and attractive class of employed as electron transport materials in perovskite solar
1
molecules for both medicinal and materials chemistry.
cell applications. Nonetheless, the studies on the photo-
β-Carbolines, composed of a pyridine conjugated with an physical properties of carboline derivatives are very limited
indole unit (pyrido[3,4-b]indoles), as a family of aza-hetero- and extensive investigations are required to extend their appli-
6
cycles, are privileged scaffolds in medicinal chemistry since cations in organic electronics.
they are the core of many molecules with potent biological and
therapeutic activities. Meanwhile, they are also essential with various electron donor and acceptor units has attracted
frameworks of a variety of bio-active natural products such as much attention from synthetic chemists. Besides the conven-
In this context, the synthesis of β-carbolines substituted
2
7
8
Harman, Bauerine A, Eudistomin A, and Plakortamine A tional Pictet–Spengler, Bischler–Napieralski and Graebe–
3
9
(
Fig. 1). β-Carbolines serve as valuable intermediates towards Ullmann reactions, a number of impressive methods have
4
the synthesis of other novel heterocycles or natural products.
been developed towards the synthesis of β-carboline
1
0–14
Recently, PyID-BTM (Fig. 1) based β-carbolines have been derivatives.
Among these approaches, alkyne-assisted
reported with remarkable photoluminescence quantum yields cyclizations of functionalized indoles have emerged as signifi-
5
and red emission upon replacing the carbazole moiety.
Thus, β-carbolines exhibit the electron deficient character-
istic of the pyridine moiety which facilitates the balance of
holes and electrons thereby enhancing the quantum efficiency
a
Department of Organic Synthesis & Process Chemistry, CSIR-Indian Institute of
Chemical Technology, Hyderabad – 500007, India. E-mail: rajireddy@iict.res.in
b
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201 002, India
c
Department of Polymers & Functional Materials, CSIR-Indian Institute of Chemical
Technology, Hyderabad 500007, India
d
University of Rennes, CNRS, Institut des Sciences Chimiques de Rennes (ISCR),
UMR 6226, F-35000 Rennes, France
†
‡
CSIR-IICT Communication No. IICT/Pubs./2019/131.
Electronic supplementary information (ESI) available: Copies of H & C NMR
1
13
spectra of all new compounds and theoretical DFT calculations. See DOI:
0.1039/c9ob01959f
1
Fig. 1 Representative molecules with the β-carboline framework.
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that tuning of the various electron-donor and acceptor groups
on β-carbolines leads to blue or green emission and potentially
promote the design of diverse efficient OLED devices.
Results and discussion
Our synthesis of β-carbolines relies on the formation of 3-pro-
pargylated indole 2-carbonyls in the presence of acid-catalysis
and aza-annulation under ammonium acetate conditions.
Optimal reaction conditions for propargylation and successive
treatment with NH
4
OAc to generate β-carbolines are reported
1
7
in Table 1. Based on literature precedence and our earlier
1
6c
Scheme 1 Representative methods for the synthesis of β-carbolines results, we have initiated the investigation with the reaction
from 2-carbonyl indoles and alkynes.
of 2-formyl indole 1a with 1,3-diphenylprop-2-yn-1-ol (2a). In
the presence of BF ·Et O (5 mol%) the reaction gave 3-propar-
3
2
gylated 2-formyl indole 3a in a promising 75% yield (Table 1,
entry 1). To our delight, the use of pTSA (5 mol%) could
provide 3a in 91% yield (Table 1, entry 2). Other catalysts such
cant methods. For instance, Larock and co-workers have
reported the palladium-catalyzed iminoannulation of acety-
lenes with tert-butylimines of halo-indolecarbonyls, which was
as FeCl
gave 3-propargylated product 3a in moderate to good yields
Table 1, entries 3–9). Next, the aza-annulation of 3a was tested
3 2 3 3 3
, CuOTf , AuCl , AgOTf, CSA, In(OTf) and Sc(OTf)
1
2
further extended by others (Scheme 1a). In addition, palla-
dium/copper-catalyzed coupling and subsequent copper-cata-
lyzed or thermal cyclization of terminal acetylenes have also
(
18
4
in the presence of NH OAc as a nitrogen source and the
1
3
been developed (Scheme 1b). Later, C–H activation based
synthetic methods involving indoloyl-ketone O-acetyl oximes
or tert-butylimines of halo-indolecarbonyls and internal
alkynes were also developed in the presence of metal-catalysts
desired product 4a was obtained in 89% yield at 80 °C, while
at room temperature there was no progress in the reaction. As
our objective was a one-pot conversion of 2-formyl indole to
β-carboline 4a without the isolation of 3a, the reaction of 1a
with 2a was performed in a one-pot approach by the successive
1
4
such as Rh and Pd (Scheme 1c). Although elegant, these
methods required the use of toxic and/or expensive transition
metals towards alkyne-based annulations. Thus, the develop-
ment of mild and metal-free reaction conditions for the syn-
thesis of β-carbolines from indole-carbonyls should be of sig-
nificant interest. In this direction, very recently base-mediated
reaction of indole-carboxaldehyde with propargyl amines has
Table 1 Optimization of reaction conditions
1
0i
been reported to access β-carbolines (Scheme 1d).
On the other hand, propargylic alcohols have received
extensive attention as versatile synthons in the synthesis of
various aromatic compounds and heterocycles, due to their
easy accessibility as well as efficacy in direct nucleophilic reac-
1
5
tions under mild reaction conditions. We have successfully
demonstrated the synthetic utility of 1-aryl propargylic alco-
hols in the preparation of various heterocyclic compounds
such as furans, carbazoles, indoles, benzothiazoles and poly-
aromatic hydrocarbons. As part of our long standing interest
in utilizing propargylic alcohols, we sought a new synthetic
possibility for rapid access to β-carbolines. Herein, we report a
facile and metal-free synthesis of diversely substituted
β-carbolines from the reaction of propargylic alcohols with
indole 2-carbonyl compounds involving one-pot sequential
propargylation/aza-annulations (Scheme 1e). The substitution
pattern of the obtained β-carbolines is entirely different in the
case of propargylic alcohols when compared with the reaction
a
Propargylation
(catalyst/time)
Yield
(%)
1
6
Entry
Cyclization
Product
1
2
3
4
5
6
7
8
3
BF ·Et
2
O/30 min
—
—
—
—
—
—
—
—
—
3a
3a
3a
3a
3a
3a
3a
3a
3a
4a
4a
4a
75
91
60
78
70
65
70
60
50
89
85
80
pTSA/60 min
FeCl /10 min
3
2
Cu(OTf) /20 min
AuCl /5 min
3
AgOTf/60 min
CSA/60 min
In(OTf)
3
/30 min
9
Sc(OTf) /30 min
3
b
10
—
4
NH OAc
with propargylic amines (Scheme 1d). To the best of our 11
knowledge, the direct use of propargylic alcohols to access
pTSA/60 min
pTSA/60 min
NH OAc
4
c
12
4
NH OAc
β-carbolines is unknown. Furthermore, we have evaluated the
a
b
c
Isolated yields. Starting material used was 3a. The reaction was
photophysical properties of these new molecules and found performed with 5 g of 1a.
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addition of pTSA (5 mol%) and after propargylation (60 min), and desilylation to give the corresponding β-carboline 4j in
NH OAc was added. We were pleased to see that the reaction 92% yield.
4
proceeded efficiently to afford 4a in 85% yield (Table 1, entry
1). Notably, this one-pot annulation was demonstrated by the present protocol was also evaluated. Interestingly, the one-pot
synthesis of β-carboline 4a on a gram scale (8.7 g, 80% yield) propargylation/annulation of 1,5-diphenylpenta-2,4-diyn-1-ol
from 5 g of 1a (Table 1, entry 12). (2k) with 1a in the presence of pTSA in acetonitrile followed by
Having the optimized conditions in hand, diverse pro- the addition of NH OAc delivered 3-allenyl-β-carboline 4k in
pargylic alcohols were first tested by reacting them with 70% yield (entry 1, Table 3) via the isomerization of the corres-
-formyl indole 1a for one-pot sequential propargylation/aza- ponding propargylated derivative to an allene towards the con-
Next, the feasibility of the use of 2,4-diyn-1-ols in this
1
4
2
annulation reactions (Table 2). Propargylic alcohols bearing jugation (may be due to the phenyl substitution on the
substituted phenyl at the C1-position 2b–2d reacted efficiently alkyne). However, 1-phenylundeca-2,4-diyn-1-ol (2l) provided
with 1-methyl-1H-indole-2-carbaldehyde (1a) to afford the 3-propargyl-β-carboline 4l in 76% yield (entry 2, Table 3)
corresponding β-carbolines 4b–4d in 89–91% yields. Next, without isomerization to an allene due to the presence of the
heteroaryl (1-tosyl-1H-indol-3-yl) and alkenyl prop-2-yn-1-ols 2e n-hexyl group on the alkyne. Encouraged by these results, we
and 2f were perfectly compatible in reacting with 1a to give extended the scope of this one-pot reaction to indol-2-yl
β-carbolines 4e (93%) and 4f (90%), respectively. Furthermore, ketones 1b, 1c and we found that they were amenable to the
propargyl alcohols bearing alkyl (2g) and cyclopropyl (2h) reaction conditions, giving 1,3,5-trisubstituted β-carbolines 4m
groups on the alkyne were used as the reaction partners with (78%) and 4n (81%), respectively (entries 3 and 4, Table 3). We
1
a to afford the desired β-carbolines 4g and 4h in good yields. were also glad to find that the N-unsubstituted indole-2-carbal-
Interestingly, the propargyl alcohol bearing a silyl group on dehyde (1d) underwent the propargylation with 2a followed by
the alkyne, 1-phenyl-3-(trimethylsilyl)prop-2-yn-1-ol (2i), was aza-annulation under the optimized reaction conditions to
also compatible for the one-pot sequential propargylation/aza- afford 3-benzyl-4-phenyl β-carboline 4o in 83% yield (entry 5,
annulation with 1a to deliver the desilylated 3-methyl- Table 3).
β-carboline 4i in 85% yield. Similarly, propargyl alcohol 2j
The versatility of this one-pot reaction was effectively
bearing tert-butyldimethylsilyl ether underwent the cyclization explored with the substrate having two propargylic alcohol
frameworks tethered to a phenyl ring 2m with 1a to furnish
1,4-bis(β-carbolinyl)-benzene 4p in 87% yield (Scheme 2).
These results certainly greatly demonstrate the structural
a
Table 2 Scope of propargylic alcohols
diversity of the resulting β-carboline compounds and show
further synthetic manipulation sites as well. This was demon-
strated by the bromination of 4a to give 6-bromo-9-methyl-4-
phenyl-9H-pyrido[3,4-b]indole (5) in 85% yield (Scheme 3),
which can be further diversified using Pd-catalyzed cross-coup-
lings. Compound 4a was also converted to its N-oxide 6 in 90%
yield (Scheme 3).
The aforementioned fruitful results encouraged us to
extend the present metal-free one-pot approach for the syn-
thesis of 5-azaindoles and 5-azabenzothiazoles, which are
common structural motifs in
a
number of bioactive
1
9,20
molecules.
Pyrrole 3-carboxaldehyde 7 was treated with
propargylic alcohols 2a and 2d under the optimized conditions
to obtain the corresponding 5-azaindoles 9a (80%) and 9b
(
1
86%), respectively (Table 4). Similarly, 5-azabenzothiazoles
0a and 10b were accessed from thiophene 3-carboxaldehyde 8
in good yields (Table 4).
1
6c,21
On the basis of the above results and literature reports,
a tentative mechanism for the described one-pot [4 + 2] annu-
lation is proposed (Scheme 4). At the beginning, generation of
carbocation A takes place from 2a in the presence of pTSA and
the addition of 1a to A leads to propargylated indole 3a via
intermediate B involving C–C bond formation, and the con-
4
densation of protonated aldehyde 3a with NH OAc as a nitro-
gen source results in the formation of imine C. The aza-cyclo-
isomerisation of C to 4a is possible via two ways: (a) through
isomerization of the propargyl compound (C) to allene-inter-
mediate D followed by C–N bond formation to E and aromati-
a
Reaction conditions: 1a (1 mmol), 2 (1.2 mmol), pTSA (5 mol%),
CN, rt, 60 min, then addition of NH OAc, 80 °C, 8–10 h.
CH
3
4
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a
Table 3 Scope of indole-2-carbonyls
a
β-Carboline (4)
Reaction time, yield
b
Entry
1
Indole-2-carbonyl (1)
Propargyl alcohol (2)
2
1a
3
4
2a
2a
5
a
b
Reaction conditions: 1 (1 mmol), 2 (1.2 mmol), pTSA (5 mol%), CH
3
CN, rt, 60 min, and then addition of NH
4
OAc, 80 °C, 8–10 h. Isolated
yields.
Table 4 Synthesis of 5-azaindoles and 5-azabenzothiazoles
Scheme 2 Synthesis of 1,4-bis(β-carbolinyl)-benzene 4p.
Computational studies
Scheme 3 Diversification of β-carboline 4a.
Density functional theory (DFT) and time-dependent density
functional theory (TDDFT) calculations were performed using
the Gaussian 09 package with a functional basis set of the
zation to 4a and (b) direct intramolecular 6-exo-dig-cyclization B3LYP/6-31G (d, p) to determine the orbital energy levels and
of alkyne (C) with imine to F followed by isomerization to oscillator strength values of β-carbolines (4a-6) in a vacuum
β-carboline 4a.
(see the ESI, Tables S1, S2 and Fig. S1‡). Energy level diagrams
After the development of the new synthetic methodology to show electron density on highest occupied molecular orbitals
access diversely substituted β-carbolines having either elec- (HOMO) and lowest unoccupied molecular orbitals (LUMO)
tron-releasing or withdrawing groups, we have carried out com- lying on the carboline moiety due to variations in the electro-
putational and photophysical studies.
negativity of donor and acceptor moieties. The resultant
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However, β-carbolines consisting of N-oxide (6) exhibit a
lower band gap compared to the –OH and –Br substituted
derivatives.
Photophysical properties
UV-visible optical absorption studies of β-carboline derivatives
−
5
were performed in chloroform at a concentration of 5 × 10
M. Absorption spectra of 4a, 4c, 4i, 4e, 4f, and 4p displayed the
absorption maxima at 290 nm and 350 nm due to the phenyl
groups at the 3-position of β-carbolines. However, 4d, 4j, and 6
possess strong electron withdrawing groups, bromides, alco-
hols and N-oxides, which affect the electrophilicity of the
π-conjugated system thus resulting in a shift in absorption
maxima towards the longer wavelength. Interestingly, the pres-
ence of a tosyl group in 4e and 4j extends the conjugation
length of the molecule and the extent of absorption by approx.
Scheme 4 Tentative reaction mechanism.
5
0 nm, respectively. Thus, the excess/deficit of electron density
plays a vital role in tuning the ground state electronic pro-
HOMO and LUMO values are in the range of −5.30 to −5.60 eV perties of the compounds (Fig. 3a).
and −1.0 to −1.4 eV. The minimum band gap of each
Subsequently, emission studies were recorded at different
22
β-carboline observed in the range of 4.0–4.4 eV indicates that excitation wavelengths of 290 and 365 nm. The emission
electron donors, acceptors and extension of π-conjugation maxima of 4p, 4c, 4e, and 4a were recorded at 377, 380, 427
influence the band gap of β-carboline systems, and thereby and 487 nm. However, electron withdrawing groups such as
should allow possible fine-tuning of their opto-electronic pro- NO and –OH linked β-carboline derivatives showed an
perties for application in organic electronics (Fig. 2). In enhancement in the fluorescence intensity with the emission
addition, DFT calculations clearly differentiate the electron maxima being recorded at 402 and 435 nm, respectively
density distribution in 4c and 4j leading to the possibilities of (Fig. 3b and Fig. S2‡). Subsequently, quantum yields of these
charge/energy or electron transfer.
derivatives were observed in the range of 0.1–0.6 wherein
Fig. 2 HOMO–LUMO energy level diagram of β-carboline derivatives calculated by the B3LYP/6-31G (d, p) method. Note: Optimized structure and
energy levels of 4e not observed due to the steric hindrance of phenyl moieties.
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Fig. 4 Photoluminescence decay profile of β-carboline derivatives 4a-6
in CHCl at an excitation wavelength of 301 nm LED source at 25 °C.
3
withdrawing capabilities of Ph/–NO groups (Fig. 4).
Nevertheless, the absorption spectra revealed no new band at a
higher wavelength region, but the fluorescence spectra showed
a considerable red shift compared to other derivatives and the
lifetime data confirmed biexponential decay profile, suggesting
that internal charge transfer is due to significant separation
between donor and acceptor groups in 4c and 4j.
Fig. 3 (a) UV-Vis absorption spectra of β-carboline derivatives 4a-6 in
at a concentration of 5 × 10− M. (b) Emission studies of
5
CHCl
3
β-carboline derivatives in CHCl
3
at an excitation wavelength of 365 nm.
Electrochemical studies
The electrochemical properties of the β-carboline derivatives
were determined in order to understand their redox behaviour
4 6
by using supporting electrolyte (0.1 M NBu PF ) with glassy
carbon, calomel electrode, and platinum wire as the respective
2
3
β-carbolines were used as a reference. Thus, these results
suggest that electron donating moieties constituting the
β-carboline system exhibit blue emission, while similar mole-
cules with electron withdrawing groups result in yellow and
green emission. In addition, extension of conjugation plays a
role in determining the electronic properties at the ground
and excited state leading to long wavelength absorption and
emission. UV-visible absorption and emission studies demon-
strated the fine tuning of electronic properties by simple sub-
stitution of electron donors, acceptors and extension of
π-conjugation.
working, reference, and auxiliary electrodes at a scan rate of
−1
2
00 mV s . 4p and 4c show oxidation potentials at 1.10 V and
1.46 V and reduction potentials at −0.63 V and −0.78 V. 4i
shows oxidation potential at 0.69 V exclusively. 6, 4d, and 4f
exhibit oxidation potentials at around 1.48 V, 1.42 V and 0.66 V
respectively. Tosyl group protected 6 and 4e show intermediary
reduction potentials at 1.29 V, −0.91, and −1.19 V respectively
(
Table 5, Fig. S2 and S3‡). Therefore, the electrochemical pro-
perties of β-carboline derivatives suggest the ease of oxidation
for 4f and 4i exclusively due to presence of phenyl groups in
β-carboline based π-conjugated systems.
Time correlated single photon counting (TCSPC) experi-
ments were performed to evaluate the life time values of
β-carboline systems upon substitution of various electron
Photostability studies
3
donors/acceptors in CHCl using a 301 nm LED source. In the
case of 4i derivative, a monoexponential decay profile was In order to investigate the stability of β-carboline derivatives,
observed with apparent values between 0.33 and 1.80 ns. we illuminated the samples with an excitation wavelength
Subsequently, addition of another methyl group and phenyl (λexc) of 350 nm. In this regard, the samples were prepared in
−
5
groups leads to an increase in lifetime values to 0.29, 2.20 ns chloroform at a concentration of 5 × 10 M at 25 °C. UV-vis
and 4.18, 12.2 ns, respectively, due to an enhanced electron absorption spectra of β-carboline derivatives showed similar
density in the π-conjugated system with a biexponential fit. spectral characteristics prior to and after exposure to UV light
However, molecules with electron acceptor moieties 6 and 4f for a time period of 1 h. The light exposed samples were
revealed the monoexponential profile with lifetime values of recorded after 24 h and no significant changes in the absorp-
3
.58 ns. Thus, amongst the synthesized β-carbolines, 4f and 6 tion spectra were observed (Fig. 5). Thus, these studies con-
exhibit a significant shift in absorption maxima and showed firmed that all the β-carboline derivatives with varying electron
blue/green emission owing to the enhanced electron donating/ donating and withdrawing groups are photostable and their
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Table 5 Photophysical, electrochemical and band gap calculations of β-carboline derivatives
b
c
e
β-Carboline
derivatives
λ
ems
τ
Oxidation
potential (V)
Reduction
potential (V)
Band gap
(eV)
Quantum
yield (φ)
a
d
ε (M cm−1
f
−1
λ
abs (nm)
(nm)
(ns)
)
4
4
4
a
c
292, 345, 365
292, 351, 366
377
377
2.64
0.29
1.30
1.465
−1.03
−0.78
4.4154
4.3377
2.0 × 10 (292 nm)
0.60
0.344
4
3.0 × 10 (292 nm)
2.20
4
4
4
i
e
305, 345, 361
292, 350, 367
427
514
1.80
4.18
0.69
1.26
−0.91
−1.45
4.424
—
2.0 × 10 (305nm)
0.301
0.302
4
2.1 × 10 (367 nm)
12.2
4
4
4
4
f
p
d
322, 369
292, 350, 367
292, 350, 366
436
380
380
3.58
0.33
0.34
0.66
1.10
1.42
−0.76
−0.63
−1.12
4.1386
4.0793
4.3656
2.1 × 10 (369 nm)
0.108
0.218
0.106
4
3.4 × 10 (292nm)
4
2.4 × 10 (292 nm)
1
.36
2.07
1.6
3.58
4
4j
292, 350, 370
265, 338
495
402
1.29
1.48
−1.19
4.1897
3.9089
4.2 × 10 (292 nm)
0.499
0.490
1
4
6
−0.91
2.6 × 10 (265 nm)
a
b
Absorption maximum values obtained from the spectra recorded in CHCl
3
.
Emission maximum values from the fluorescence spectra
c
d
measured in CHCl
dyes performed in CHCl
3
at 25 °C. Photoluminescence decay profiles analysed in CHCl
3
at 25 °C using a 301 nm LED source. The redox potentials of
with 0.1 M tetrabutylammonium hexafluorophosphate (TBAPF
) at a scan rate of 200 mV s− (vs. SCE). Band gap obtained
1
e
3
6
f
−5
from the optimized structures using EHOMO − ELUMO. Molar extinction co-efficient (ε) calculated by using concentration 5 × 10 M and path length:
1
cm.
port properties in these types of molecules. Therefore, optical
and electrochemical properties of β-carboline systems could
contribute to the design of novel carbolines for improving the
performance of diverse LEDS and organic electronics.
Experimental
General methods
Oven-dried glass apparatus was used to perform all the reac-
tions. The reactions were monitored by thin-layer chromato-
graphy carried out on silica plates using UV-light and anisalde-
hyde for visualization. Column chromatography was per-
formed on silica gel (60–120 mesh) using n-hexane and ethyl
acetate as eluents. Evaporation of solvents was done under
reduced pressure at a temperature less than 45 °C. IR spectra
were recorded using Perkin-Elmer 683 and Nicolet Nexus 670
Fig. 5 UV-Vis absorption spectra of β-carboline derivatives in CHCl
upon exposure to UV light.
3
inherent electronic features remain unaffected during
2
4
1
13
1
illumination.
spectrometers. H and C{ H} NMR spectra were recorded in
CDCl solvent on a 300 MHz, 500 MHz and 400 MHz NMR
3
spectrometer. Chemical shifts δ and coupling constants J are
given in ppm (parts per million) and Hz (hertz) respectively.
Chemical shifts are reported relative to residual solvent as an
Conclusions
1
13
1
In summary, we have demonstrated a novel one-pot reaction to internal standard for H and C (CDCl : δ 7.26 ppm for H
3
1
3
synthesize the diversely substituted β-carboline derivatives with and 77.0 ppm for C). High resolution mass spectra (HRMS)
+
electron-donor and acceptor moieties. This straightforward [ESI ] were obtained using either a TOF or a double focusing
approach supplements the existing methods to access spectrometer, micro mass VG 70-70H or LC/MSD trap SL
β-carbolines. Furthermore, the developed strategy was extended spectrometer operating at 70 eV using a direct inlet system.
2
5
26
27
28
16b
to the synthesis of 5-azaindoles and 5-azabenzothiazoles.
2-Acyl indoles 1a, 1b, 1c, 1d; 3-formyl pyrrole 7
1
6b
Theoretical and photophysical properties suggested that com- and 3-formyl thiophene 8;
and propargylic alcohols (2a–
1
6a
29
pounds 4a-6 consisting of electron donor/acceptor moieties 2k) and 2m were prepared using the literature procedures.
such as Ph and –NO on β-carboline systems strongly influenced Analytical data of all these compounds were correlated with
their HOMO and LUMO energy levels which affects the ground the corresponding reported data.
and excited state electronic properties thereby leading to the
1
-(Naphthalen-1-yl)undeca-2,4-diyn-1-ol (2l)
extended absorption and blue or green emission observed.
Cyclic voltammetric studies revealed that ease of redox behavior To a stirred solution of 1-(naphthalen-1-yl)prop-2-yn-1-ol Int-
3
0
in 4f, 4d and 6 derivatives facilitates enhanced electron trans-
a
(500 mg, 2.74 mmol) in dry toluene (10 mL) were added
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CuCl (15 mol%, 40 mg), NH
2
OH·HCl (30 mol%, 56 mg), ducts (for reaction times and yields of products, see Schemes
3
1
n-BuNH2 (4.12 mmol, 0.4 mL), and 1-bromooct-1-yne
4.12 mmol, 774 mg) (prepared using the known procedure
2–3 and Tables 2–4).
(
given in ref. 8) at 0 °C, and the solution was warmed to room 3-Benzyl-9-methyl-4-phenyl-9H-pyrido[3,4-b] indole (4a)
temperature and stirred for 2 h. The reaction mixture was
quenched with 3N HCl and extracted with EtOAc (2 × 10 mL).
The combined organic layers were washed with brine (15 mL),
Following the general procedure, 1a (100 mg, 0.62 mmol) in
acetonitrile was allowed to react with 2a (156 mg, 0.75 mmol)
in the presence of pTSA (5 mg, 0.03 mmol) followed by the
dried over Na SO , and concentrated. The residue was purified
2
4
addition of NH
4
OAc (58 mg, 0.75 mmol) to afford β-carboline
= 0.5
petroleum ether : EtOAc = 1 : 1); H NMR (400 MHz, CDCl3)
δ 8.88 (s, 1H), 7.53–7.45 (m, 4H), 7.40 (d, J = 8.3 Hz, 1H),
by flash column chromatography on silica gel (5% EtOAc in
petroleum ether) to afford propargylic alcohol 2l in 82% yield
4a in 85% yield (183 mg). Yellow solid, mp 126–128 °C, R
f
1
(
(
652 mg). Pale brown viscous liquid, Rf = 0.5 (petroleum
1
ether : EtOAc = 9 : 1); H NMR (500 MHz, CDCl
3
) δ 8.20 (d, J =
7
1
7
.33–7.29 (m, 2H), 7.16 (t, J = 7.3 Hz, 2H), 7.10 (t, J = 7.2 Hz,
8
7
8
5
0
.5 Hz, 1H), 7.84 (dd, J = 8.4, 0.9 Hz, 1H), 7.78 (dd, J = 17.0,
H), 7.03 (d, J = 7.1 Hz, 2H), 6.93 (t, J = 7.2 Hz, 1H), 6.87 (d, J =
.6 Hz, 2H), 7.52 (ddd, J = 8.4, 6.8, 1.5 Hz, 1H), 7.47 (ddd, J =
.0, 6.9, 1.2 Hz, 1H), 7.41 (dd, J = 8.2, 7.2 Hz, 1H), 6.08 (d, J =
.9 Hz, 1H), 2.63 (dd, J = 6.0, 3.4 Hz, 1H), 2.25 (td, J = 7.0,
.7 Hz, 2H), 1.54–1.46 (m, 2H), 1.39–1.32 (m, 2H), 1.30–1.21
13
1
.9 Hz, 1H), 4.18 (s, 2H), 3.95 (s, 3H); C{ H} NMR (75 MHz,
) δ 145.2, 143.1, 139.7, 136.4, 135.4, 131.3, 129.4, 129.2,
29.0, 128.9, 128.5, 128.2, 127.5, 126.0, 123.8, 120.8, 120.1,
09.2, 39.2, 29.7; IR (KBr): νmax = 3058, 2925, 2360, 1451, 752,
CDCl
3
1
1
7
1
3
1
(
m, 4H), 0.87 (t, J = 7.1 Hz, 3H); C{ H} NMR (125 MHz,
CDCl ) δ 134.9, 133.9, 130.3, 129.4, 128.7, 126.5, 125.9, 125.2,
24.7, 123.7, 82.8, 74.4, 72.4, 64.4, 63.3, 31.2, 28.4, 28.0, 22.4,
−1
+
02 cm ; MS (ESI): m/z 349 (M + H) ; HRMS (ESI): m/z calcd
3
+
for C H N (M + H) : 349.1699, found: 349.1714.
2
5
21 2
1
1
7
9.3, 14.0; IR (KBr): νmax = 3361, 2929, 2252, 1457, 1223, 1003,
3
(
-Benzyl-4-(4-methoxyphenyl)-9-methyl-9H-pyrido[3,4-b]indole
4b)
Following the general procedure, 1a (100 mg, 0.62 mmol) in
-(1,3-Diphenylprop-2-yn-1-yl)-1-methyl-1H-indole-2-carbaldehyde acetonitrile was allowed to react with 2b (175 mg, 0.75 mmol)
86 cm− ; MS (ESI): m/z 313 (M + Na) ; HRMS (EI): m/z calcd
1
+
+
for C H O (M) : 290.1670, found: 290.1663.
2
1
22
3
(3a)
in the presence of pTSA (5 mg, 0.03 mmol) followed by the
addition of NH OAc (58 mg, 0.75 mmol) to afford β-carboline
4
A solution of 1a (100 mg, 0.62 mmol) in acetonitrile at room
temperature was allowed to react with 1,3-diphenylprop-2-yn-1-
ol (2a, 156 mg, 0.75 mmol) and pTSA (5 mg, 0.03 mmol). After
4
b in 89% yield (208 mg). Pale yellow liquid, R = 0.5 (pet-
f
1
roleum ether : EtOAc = 1 : 1); H NMR (300 MHz, CDCl
3
) δ 8.87
(
s, 1H), 7.49 (ddd, J = 8.2, 5.1, 3.1 Hz, 1H), 7.41 (d, J = 8.3 Hz,
3
0 min, the solvent was evaporated under reduced pressure
1
2
H), 7.24–7.09 (m, 5H), 7.04 (d, J = 8.4 Hz, 4H), 6.97 (d, J =
.8 Hz, 2H), 4.19 (s, 2H), 3.94 (s, 3H), 3.94 (s, 3H); C{ H}
and the residue was purified by column chromatography on
silica gel (5% EtOAc in petroleum ether) to afford propargy-
1
3
1
NMR (75 MHz, CDCl ) δ 159.2, 147.7, 142.1, 141.5, 135.7,
3
lated indole 3a in 95% yield (207 mg). Pale yellow solid,
1
130.6, 130.2, 130.1, 128.8, 128.2, 128.0, 127.8, 125.6, 123.5,
mp 118–120 °C, R
f
= 0.5 (petroleum ether : EtOAc = 1 : 9); H
1
2
21.3, 119.2, 114.2, 108.8, 55.3, 40.7, 29.3; IR (KBr): νmax =
NMR (400 MHz, CDCl ) δ 10.43 (s, 1H), 7.89 (d, J = 8.2 Hz, 1H),
3
−1
928, 2360, 1612, 1507, 1246, 1033, 749 cm ; MS (ESI): m/z
7
7
6
.56 (d, J = 7.9 Hz, 2H), 7.49–7.43 (m, 2H), 7.42–7.35 (m, 2H),
+
+
379 (M + H) ; HRMS (ESI): m/z calcd for C H N O (M + H) :
26 23 2
.35–7.28 (m, 5H), 7.23 (t, J = 7.3 Hz, 1H), 7.14 (ddd, J = 8.0,
1
3
1
379.1791, found: 379.1789.
.5, 1.3 Hz, 1H), 6.07 (s, 1H), 4.09 (s, 3H); C{ H} NMR
) δ 182.3, 140.4, 139.7, 131.7, 130.5, 128.6,
28.3, 128.2, 127.3, 127.2, 127.0, 125.1, 123.1, 122.3, 120.8,
10.4, 89.2, 85.0, 33.2, 31.8; IR (KBr) ν = 3060, 1659, 1479,
(100 MHz, CDCl
3
3
-Benzyl-9-methyl-4-(3,4,5-trimethoxyphenyl)-9H-pyrido-[3,4-b]
indole (4c)
203, 889, 747, 699 cm ; MS (ESI): m/z 372 (M + Na) ; HRMS Following the general procedure, 1a (100 mg, 0.62 mmol) in
1
1
1
max
−
1
+
+
(ESI): m/z calcd for C25
H
19NONa (M + Na) : 372.1364, found: acetonitrile was allowed to react with 2c (224 mg, 0.75 mmol)
in the presence of pTSA (5 mg, 0.03 mmol) followed by the
3
72.1364.
addition of NH
4
OAc (58 mg, 0.75 mmol) to afford β-carboline
= 0.5 (pet-
roleum ether : EtOAc = 7 : 3); H NMR (300 MHz, CDCl ) δ 8.90
General procedure for the one-pot synthesis of β-carbolines
4a–4o)
4c in 89% yield (241 mg). Pale brown liquid, R
f
(
1
3
To a stirred solution of 2-acyl indole 1 (1.0 mmol) and pro- (s, 1H), 7.56–7.48 (m, 1H), 7.42 (d, J = 8.3 Hz, 1H), 7.20–7.13
pargylic alcohol 2 (1.2 mmol) in 10 mL of acetonitrile was (m, 2H), 7.10 (d, J = 7.0 Hz, 1H), 7.07–6.97 (m, 4H), 6.43 (s,
1
3
1
added pTSA (5 mol%) at room temperature and stirred for 2H), 4.23 (s, 2H), 3.99 (s, 3H), 3.96 (s, 3H), 3.67 (s, 6H); C{ H}
0 min. Then, NH OAc (1.2 mmol) was added to the reaction NMR (75 MHz, CDCl ): δ 153.4, 147.1, 142.2, 141.6, 137.5,
6
4
3
mixture and stirred at 80 °C in a silicone oil bath for 8–11 h. 135.7, 133.1, 130.4, 130.0, 128.7, 128.1, 128.0, 125.6, 123.6,
After the completion of the reaction (monitored by TLC) the 121.0, 119.5, 108.9, 106.3, 61.1, 56.0, 41.1, 29.4; IR (KBr):
−
1
mixture was concentrated under reduced pressure. The crude
νmax = 2926, 1447, 1369, 1174, 1369, 751, 665 cm ; MS (ESI):
+
product was purified by column chromatography on silica gel m/z 439 (M + H) ; HRMS (ESI): m/z calcd for C28
27 2 3
H N O
+
(EtOAc–hexanes) to afford the corresponding β-carboline pro- (M + H) : 439.2016, found: 439.2014.
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Paper
3-Benzyl-4-(4-bromophenyl)-9-methyl-9H-pyrido[3,4-b]-indole (4d) 3-Butyl-9-methyl-4-phenyl-9H-pyrido[3,4-b] indole (4g)
Following the general procedure, 1a (100 mg, 0.62 mmol) in Following the general procedure, 1a (100 mg, 0.62 mmol) in
acetonitrile was allowed to react with 2d (214 mg, 0.75 mmol) acetonitrile was allowed to react with 2g (131 mg, 0.75 mmol)
in the presence of pTSA (5 mg, 0.03 mmol) followed by the in the presence of pTSA (5 mg, 0.03 mmol) followed by the
addition of NH
4
OAc (58 mg, 0.75 mmol) to afford β-carboline addition of NH
4
OAc (58 mg, 0.75 mmol) to afford β-carboline
= 0.5 (pet-
4
d in 91% yield (240 mg). Light green solid, mp 150–152 °C, 4g in 83% yield (161 mg). Light yellow liquid, R
f
1
1
R = 0.5 (petroleum ether : EtOAc = 1 : 1); H NMR (500 MHz, roleum ether : EtOAc = 7 : 3); H NMR (300 MHz, CDCl ) δ 8.84
f
3
CDCl
3
) δ 8.89 (s, 1H), 7.66–7.61 (m, 2H), 7.50 (ddd, J = 8.3, 5.6, (s, 1H), 7.62–7.41 (m, 5H), 7.40–7.34 (m, 2H), 6.93 (t, J =
1
1
7
.3 Hz, 1H), 7.42 (d, J = 8.3 Hz, 1H), 7.17 (ddd, J = 7.7, 4.1, 7.4 Hz, 1H), 6.85 (d, J = 7.8 Hz, 1H), 3.92 (s, 3H), 2.80–2.72 (t,
.9 Hz, 4H), 7.13–7.08 (m, 1H), 7.04–6.97 (m, 3H), 6.93 (d, J = 2H), 1.73–1.59 (m, 2H), 1.33–1.25 (m, 2H), 0.81 (t, J = 7.3 Hz,
1
3
1
13
1
3
.9 Hz, 1H), 4.16 (s, 2H), 3.95 (s, 3H); C{ H} NMR (75 MHz, 3H); C{ H} NMR (75 MHz, CDCl ) δ 149.1, 142.1, 138.4,
CDCl ): δ 146.6, 142.4, 140.7, 136.6, 135.6, 132.0, 131.8, 131.2, 135.4, 130.1, 129.6, 129.3, 128.8, 127.7, 123.4, 121.2, 119.1,
3
1
1
1
30.5, 129.9, 129.2, 128.7, 128.4, 128.2, 125.8, 123.3, 122.2, 108.7, 34.4, 33.1, 29.3, 22.7, 13.9; IR (KBr): ν : 2925, 2861,
max
20.8, 120.3, 119.6, 109.1, 40.4, 29.5; IR (KBr): νmax = 2359, 1447, 1295, 1031, 747, 702 cm− ; MS (ESI): m/z 315 (M + H) ;
1
+
−
1
+
489, 1447, 1072, 826, 752, 705 cm ; MS (ESI): m/z 427 HRMS (ESI): m/z calcd for C H N Na (M + Na) : 337.1675,
2
2
22 2
+
+
(M + H) ; HRMS (ESI): m/z calcd for C H BrN (M + H) : found: 337.1686.
25 20 2
4
27.0804, found: 427.0823.
3-(Cyclopropylmethyl)-9-methyl-4-phenyl-9H-pyrido[3,4-b] indole
3
-Benzyl-9-methyl-4-(1-tosyl-1H-indol-2-yl)-9H-pyrido[3,4-b]-indole (4h)
(4e)
Following the general procedure, 1a (100 mg, 0.62 mmol) in
Following the general procedure, 1a (100 mg, 0.62 mmol) in acetonitrile was allowed to react with 2h (129 mg, 0.75 mmol)
acetonitrile was allowed to react with 2e (302 mg, 0.75 mmol) in the presence of pTSA (5 mg, 0.03 mmol) followed by the
in the presence of pTSA (5 mg, 0.03 mmol) followed by the addition of NH
4
OAc (58 mg, 0.75 mmol) to afford β-carboline
= 0.5 (pet-
e in 93% yield (311 mg). Light brown solid, mp 228–230 °C, roleum ether : EtOAc = 7 : 3); H NMR (500 MHz, CDCl ): δ 8.88
addition of NH OAc (58 mg, 0.75 mmol) to afford β-carboline 4h in 90% yield (174 mg). Pale yellow liquid; R
f
4
1
4
3
1
R = 0.5 (petroleum ether : EtOAc = 1 : 1); H NMR (400 MHz, (s, 1H), 7.58–7.51 (m, 3H), 7.49 (ddd, J = 8.2, 6.4, 2.9 Hz, 1H),
f
CDCl ) δ 8.93 (s, 1H), 8.18 (d, J = 8.4 Hz, 1H), 7.77 (d, J = 7.43–7.39 (m, 3H), 6.95–6.91 (m, 1H), 6.83 (d, J = 7.9 Hz, 1H),
3
8
2
1
1
.4 Hz, 2H), 7.52 (s, 1H), 7.46–7.35 (m, 3H), 7.20 (d, J = 8.1 Hz, 3.96 (s, 3H), 2.71 (d, J = 6.8 Hz, 2H), 1.13–1.06 (m, 1H),
1
3
1
H), 7.12–7.03 (m, 4H), 6.87 (t, J = 7.3 Hz, 3H), 6.65 (ddd, J = 0.42–0.35 (m, 2H), 0.11–0.07 (m, 2H); C{ H} NMR (125 MHz,
9.2, 13.0, 4.4 Hz, 2H), 4.18 (d, J = 14.7 Hz, 1H), 4.01 (d, J = CDCl ) δ 148.4, 142.2, 138.3, 135.4, 129.9, 129.6, 129.5, 128.8,
C{ H} NMR 127.9, 127.8, 123.4, 121.2, 119.2, 108.8, 38.9, 29.4, 11.7, 4.6;
3
1
3
1
4.7 Hz, 1H), 3.96 (s, 3H), 2.37 (s, 3H);
−
1
(
125 MHz, CDCl ): δ 149.0, 145.0, 142.1, 141.1, 135.6, 135.2, IR (KBr): νmax = 2926, 1620, 1446, 1020, 749, 702 cm ; MS
3
+
1
1
1
1
35.1, 131.1, 130.6, 129.9, 128.8, 128.5, 128.1, 128.0, 126.9, (ESI): m/z 313 (M + H) ; HRMS (ESI): m/z calcd for C22
H
21
N
2
+
25.7, 125.2, 124.7, 123.7, 123.2, 120.7, 120.5, 120.1, 120.0, (M + H) : 313.1699, found: 313.1712.
19.3, 114.0, 108.9, 41.1, 29.4, 21.6; IR (KBr): ν
446, 1370, 1174, 1123, 750 cm ; MS (ESI): m/z 542 (M + H) ;
= 2360,
max
−1
+
3,9-Dimethyl-4-phenyl-9H-pyrido[3,4-b] indole (4i)
+
HRMS (ESI): m/z calcd for C34
H
28
N
3
O
2
S (M + H) : 542.1897, Following the general procedure, 1a (100 mg, 0.62 mmol) in
acetonitrile was allowed to react with 2i (153 mg, 0.75 mmol)
found: 542.1923.
in the presence of pTSA (5 mg, 0.03 mmol) followed by the
(E)-3-Benzyl-9-methyl-4-styryl-9H-pyrido[3,4-b]indole (4f)
addition of NH OAc (58 mg, 0.75 mmol) to afford β-carboline
4
4
(
i in 85% yield (143 mg). Yellow solid, mp 88–90 °C, R
f
= 0.5
petroleum ether : EtOAc = 7 : 3); H NMR (500 MHz, CDCl
δ 8.79 (s, 1H), 7.59–7.52 (m, 3H), 7.48 (dd, J = 8.3, 4.2 Hz, 1H),
.42–7.38 (m, 3H), 6.97–6.92 (m, 2H), 3.94 (s, 3H), 2.50 (s, 3H);
Following the general procedure, 1a (100 mg, 0.62 mmol) in
acetonitrile was allowed to react with 2f (176 mg, 0.75 mmol)
in the presence of pTSA (5 mg, 0.03 mmol) followed by the
1
3
)
7
addition of NH
4
OAc (58 mg, 0.75 mmol) to afford β-carboline
= 0.3 (pet-
roleum ether : EtOAc = 1 : 1); H NMR (400 MHz, CDCl ) δ 8.81
1
3
1
C{ H} NMR (75 MHz, CDCl
3
) δ 144.9, 142.2, 138.6, 135.7,
4
f in 90% yield (208 mg). Pale yellow liquid, R
f
1
129.8, 129.6, 129.1, 128.9, 127.8, 127.7, 123.4, 121.0, 119.1,
3
1
7
08.8, 29.3, 21.9; IR (KBr): νmax = 3052, 2924, 1619, 1447, 1025,
(
1
(
3
1
1
1
7
s, 1H), 8.24 (d, J = 8.0 Hz, 1H), 7.59–7.51 (m, 4H), 7.44 (dd, J =
3.0, 5.8 Hz, 3H), 7.38–7.31 (m, 2H), 7.25–7.21 (m, 3H), 7.16
dt, J = 7.2, 5.2 Hz, 2H), 6.92 (d, J = 16.6 Hz, 1H), 4.46 (s, 2H),
.94 (s, 3H); C{ H} NMR (125 MHz, CDCl ) δ 147.5, 142.2,
3
41.1, 136.9, 136.0, 135.9, 129.7, 128.9, 128.8, 128.3, 128.1,
27.9, 127.3, 127.0, 126.6, 125.8, 124.2, 124.0, 121.4, 119.4,
48, 700 cm− ; MS (ESI): m/z 272 (M + H) ; HRMS (ESI): m/z
1
+
+
calcd for C H N (M + H) : 273.1386, found: 273.1384.
19 17 2
1
3
1
2-(9-Methyl-4-(1-tosyl-1H-indol-2-yl)-9H-pyrido [3,4-b] indol-3-yl)
ethan-1-ol (4j)
09.0, 41.4, 29.4; IR (KBr): νmax = 3027, 2359, 1612, 1485, 1447, Following the general procedure, 1a (100 mg, 0.62 mmol) in
48, 700 cm− ; MS (ESI): m/z 375 (M + H) ; HRMS (ESI): m/z acetonitrile was allowed to react with 2j (353 mg, 0.75 mmol)
1
+
+
calcd for C H N (M + H) : 375.1856, found: 375.1859.
in the presence of pTSA (5 mg, 0.03 mmol) followed by the
2
7
23 2
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Paper
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addition of NH
4
OAc (58 mg, 0.75 mmol) to afford β-carboline 3-Benzyl-1,9-dimethyl-4-phenyl-9H-pyrido[3,4-b]indole (4m)
4
j in 92% (284 mg). Pale yellow solid, mp 130–132 °C, R = 0.5
f
Following the general procedure, 1-(1-methyl-1H-indol-2-yl)
ethanone 1b (100 mg, 0.58 mmol) in acetonitrile at room temp-
erature was allowed to react with 2a (144 mg, 0.69 mmol) and
1
(
petroleum ether : EtOAc = 2 : 8); H NMR (400 MHz, CDCl
δ 8.84 (s, 1H), 8.21 (d, J = 8.4 Hz, 1H), 7.91–7.82 (m, 2H), 7.67
s, 1H), 7.52–7.37 (m, 3H), 7.33–7.23 (m, 2H), 7.21–7.09 (m,
3
)
(
pTSA (5 mg, 0.03 mmol) followed by the addition of NH
53 mg, 0.69 mmol) to afford compound 4m in 78% yield
164 mg). Light brown solid, mp 110–112 °C, R = 0.5 (petroleum
4
OAc
1
H), 7.06–6.98 (m, 1H), 6.71–6.63 (m, 2H), 3.97 (s, 3H),
(
1
3
1
3
.92–3.87 (m, 2H), 2.99–2.78 (m, 2H), 2.42 (s, 3H); C{ H}
(
f
NMR (75 MHz, CDCl ) δ 148.3, 145.2, 142.6, 135.5, 135.3,
1
3
ether : EtOAc = 7 : 3); H NMR (300 MHz, CDCl
3
) δ 7.50–7.43 (m,
H), 7.38 (d, J = 8.2 Hz, 1H), 7.23 (d, J = 3.8 Hz, 2H), 7.19–7.07 (m,
H), 7.05–6.99 (m, 2H), 6.93–6.85 (m, 1H), 6.74 (d, J = 8.0 Hz, 1H),
1
1
30.2, 130.0, 129.3, 128.7, 126.9, 125.5, 124.9, 124.0, 123.3,
20.3, 119.6, 119.2, 114.2, 109.1, 62.2, 34.9, 29.5, 21.6;
4
3
4
−
1
IR (KBr): νmax = 2925, 2359, 1175, 759, 669 cm ; MS (ESI): m/z
4
13
1
.16 (s, 3H), 4.11 (s, 2H), 3.15 (s, 3H); C{ H} NMR (125 MHz,
+
26 3 3
96 (M + H) ; HRMS (ESI): m/z calcd for C29H N O S
CDCl ) δ 146.1, 142.5, 141.4, 140.1, 138.2, 134.5, 129.6, 128.8,
3
+
(M + H) : 496.1687, found: 496.1695.
1
1
1
28.7, 128.6 (2C), 128.2, 127.8, 127.6, 127.4, 125.4, 123.2, 121.3,
19.1, 109.0, 40.6, 32.2, 23.8; IR (KBr): νmax = 3026, 1610, 1439,
−
1
+
9-Methyl-4-phenyl-3-(3-phenylpropa-1,2-dien-1-yl)-9H-pyrido[3,4-b]
300, 908, 734, 702 cm ; MS (ESI): m/z 363 (M + H) ; HRMS
+
indole (4k)
(ESI): m/z calcd for C H N (M + H) : 363.1861, found: 363.1863.
2
6 23 2
Following the general procedure, 1a (100 mg, 0.62 mmol) in
acetonitrile was allowed to react with 2k (175 mg, 0.75 mmol)
3-Benzyl-1-ethyl-9-methyl-4-phenyl-9H-pyrido[3,4-b]indole (4n)
in the presence of pTSA (5 mg, 0.03 mmol) followed by the Following the general procedure, 1c (100 mg, 0.53 mmol) in
addition of NH OAc (58 mg, 0.75 mmol) to afford β-carboline acetonitrile was allowed to react with 2a (133 mg, 0.64 mmol) in
4
4
k in 70% yield (162 mg). Brown viscous liquid, R
f
= 0.6 (pet- the presence of pTSA (4 mg, 0.03 mmol) followed by the addition
1
roleum ether : EtOAc = 4 : 1); H NMR (400 MHz, CDCl ) δ 8.89 of NH OAc (49 mg, 0.64 mmol) to afford β-carboline 4n in 81%
3
4
(
s, 1H), 7.59–7.55 (m, 1H), 7.51–7.47 (m, 4H), 7.45–7.43 (m, yield (161 mg). Pale yellow viscous liquid, R = 0.5 (petroleum
f
1
1
7
6
H), 7.39 (s, 1H), 7.32–7.27 (m, 3H), 7.25 (d, J = 1.5 Hz, 1H), ether : EtOAc = 4 : 1); H NMR (400 MHz, CDCl ) δ 7.49–7.45 (m,
3
.18–7.13 (m, 1H), 6.98–6.94 (m, 2H), 6.75 (d, J = 6.6 Hz, 1H), 3H), 7.44–7.41 (m, 1H), 7.38 (d, J = 8.3 Hz, 1H), 7.25–7.22 (m, 2H),
1
3
1
.49 (d, J = 6.6 Hz, 1H), 3.93 (s, 3H); C{ H} NMR (100 MHz, 7.14 (ddd, J = 7.4, 4.4, 1.4 Hz, 2H), 7.09 (dt, J = 5.2, 2.1 Hz, 1H),
) δ 209.5, 142.0, 140.4, 137.6, 135.6, 134.1, 131.3, 129.7, 7.05 (dd, J = 6.5, 5.0 Hz, 2H), 6.88 (ddd, J = 8.0, 6.9, 1.1 Hz, 1H),
29.6, 129.5, 128.9, 128.8, 128.4, 128.0, 127.9, 127.5, 127.0, 6.75–6.72 (m, 1H), 4.13 (s, 3H), 4.11 (s, 2H), 3.45 (q, J = 7.5 Hz,
CDCl
1
1
ν
3
3
3
1
3
1
26.8, 123.4, 121.1, 119.5, 109.0, 97.6, 97.5, 29.3; IR (KBr): 2H), 1.52 (t, J = 7.5 Hz, 3H); C{ H} NMR (100 MHz, CDCl )
3
−
1
max = 3058, 1639, 1454, 1253, 958, 748 cm ; MS (ESI): m/z δ 146.1, 145.3, 142.6, 141.4, 138.3, 133.6, 129.7, 128.8, 128.6 (2C),
73 (M + H) ; HRMS (ESI): m/z calcd for C H N (M + H) : 128.3, 127.8, 127.6, 127.4, 125.4, 123.2, 121.4, 119.1, 109.0, 40.6,
+
+
2
7
21 2
73.1705, found: 373.1703.
32.2, 29.0, 14.8; IR (KBr): ν
max
= 3061, 1659, 1448, 1257, 1030,
−1
+
7
52, 702 cm ; MS (ESI): m/z 377 (M + H) ; HRMS (ESI): m/z calcd
+
9
-Methyl-4-(naphthalen-1-yl)-3-(non-2-yn-1-yl)-9H-pyrido- [3,4-b] for C27
H
25
N
2
(M + H) : 377.2018, found: 377.2021.
indole (4l)
3
-Benzyl-4-phenyl-9H-pyrido[3,4-b]indole (4o)
Following the general procedure, 1a (100 mg, 0.62 mmol) in
acetonitrile at room temperature was allowed to react with 2l
Following the general procedure, 1d (100 mg, 0.69 mmol) in
acetonitrile was allowed to react with 2a (171 mg, 0.82 mmol)
in the presence of pTSA (5.9 mg, 0.03 mmol) followed by the
addition of NH OAc (49 mg, 0.64 mmol) to afford β-carboline
f
4o in 83% yield (191 mg). Yellow liquid, R = 0.5 (petroleum
(218 mg, 0.75 mmol) in the presence of pTSA (5 mg,
0
.03 mmol) followed by the addition of NH
4
OAc (58 mg,
0
.75 mmol) to afford β-carboline 4l in 76% yield (203 mg). Pale
4
1
red viscous liquid, R
f
= 0.3 (petroleum ether : EtOAc = 7 : 3); H
) δ 8.97 (s, 1H), 8.04 (d, J = 8.3 Hz, 1H),
.97 (d, J = 8.2 Hz, 1H), 7.65 (dd, J = 8.2, 7.0 Hz, 1H), 7.56 (dd,
J = 7.0, 1.1 Hz, 1H), 7.49–7.44 (m, 1H), 7.41–7.34 (m, 3H),
.25–7.21 (m, 1H), 6.73 (ddd, J = 8.0, 6.7, 1.4 Hz, 1H), 6.40 (d,
J = 8.0 Hz, 1H), 3.96 (s, 3H), 3.64 (dt, J = 17.2, 2.4 Hz, 1H), 3.55
1
ether : EtOAc = 1 : 1); H NMR (500 MHz, CDCl
3
) δ 8.89 (s, 1H),
NMR (500 MHz, CDCl
3
8.39 (s, 1H), 7.54–7.48 (m, 3H), 7.46–7.39 (m, 2H), 7.33 (ddd,
7
J = 5.5, 4.9, 3.5 Hz, 2H), 7.17 (dd, J = 7.9, 6.5 Hz, 2H), 7.10 (dd,
J = 8.6, 5.9 Hz, 1H), 7.06–7.01 (m, 2H), 6.94 (ddd, J = 8.1, 6.1,
7
1
3
1
2
(
.0 Hz, 1H), 6.85 (d, J = 8.0 Hz, 1H), 4.17 (s, 2H); C{ H} NMR
100 MHz, CDCl ) δ 147.5, 141.2, 140.8, 137.9, 134.4, 132.1,
130.5, 129.5, 128.8, 128.1, 128.03, 127.9, 125.6, 123.4, 121.7,
(
(
dt, J = 17.2, 2.4 Hz, 1H), 2.03 (tt, J = 7.2, 2.3 Hz, 2H), 1.38–1.31
m, 2H), 1.28–1.17 (m, 6H), 0.84 (t, J = 7.1 Hz, 3H); C{ H}
3
1
3
1
1
7
19.8, 111.2, 40.7; IR (KBr): ν
= 3026, 1616.62, 1435, 1331,
NMR (100 MHz, CDCl ) δ 145.0, 142.1, 135.9, 135.0, 133.7,
max
3
50, 701 cm− ; MS (ESI): m/z 335 (M + H) ; HRMS (ESI): m/z
1
+
1
1
2
1
31.8, 130.8, 128.6, 128.5, 128.2, 127.8, 127.4, 127.2, 126.3,
26.1, 125.7, 125.6, 123.2, 120.9, 119.3, 108.8, 81.9, 77.8, 31.3,
9.4, 28.8, 28.5, 25.5, 22.5, 18.9, 14.0; IR (KBr): ν
+
calcd for C24
H
19
N
2
(M + H) : 335.1551, found: 335.1548.
= 2926,
max
−
1
1,4-Bis(3-benzyl-5-methyl-5H-pyrido[4,3-b]indol-4-yl)-benzene (4p)
618, 1449, 1335, 1251, 1011, 749 cm ; MS (ESI): m/z 431 (M +
+
+
H) ; HRMS (ESI): m/z calcd for C31
H
31
N
2
(M + H) : 431.2487, Following the general procedure, 1a (100 mg, 0.62 mmol) in
acetonitrile was allowed to react with 2m (125 mg, 0.37 mmol)
found: 431.2484.
9300 | Org. Biomol. Chem., 2019, 17, 9291–9304
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in the presence of pTSA (5 mg, 0.03 mmol) followed by the General procedure for 5-azaindoles and 5-azabenzothiazoles (9a,
addition of NH OAc (58 mg, 0.75 mmol) to afford β-carboline 9b and 10a, 10b)
4
4
f
p in 60% yield (229 mg). Yellow solid, mp 130–132 °C, R =
To a stirred solution of 3-formyl pyrrole or 3-formyl thiophene
1.0 mmol) and propargylic alcohol (1.2 mmol) in 10 mL of
acetonitrile was added pTSA (5 mol%) at room temperature
and stirred for 30–60 min. Then, NH OAc (1.2 mmol) was
added to the reaction mixture at rt and continuously stirred at
0 °C for 8–10 h. After the completion of the reaction (moni-
tored by TLC) the mixture was concentrated under reduced
pressure. The crude product was purified by column chromato-
graphy on silica gel (EtOAc–hexanes) to afford the corres-
ponding 5-azaindoles and 5-azabenzothiazoles respectively
1
0
3
.5 (DCM : methanol = 9.5 : 0.5); H NMR (400 MHz, CDCl )
(
δ 8.96 (s, 1H), 8.96 (s, 1H), 7.59–7.51 (m, 2H), 7.49 (s, 1H), 7.47
(
(
(
(
1
1
9
s, 4H), 7.46 (s, 1H), 7.45 (d, J = 3.5 Hz, 1H), 7.42 (s, 1H), 7.21
d, J = 7.0 Hz, 3H), 7.17–7.08 (m, 8H), 7.01–6.96 (m, 1H), 4.39
s, 2H), 4.33 (s, 2H), 4.01 (s, 3H), 4.00 (s, 3H); C{ H} NMR
100 MHz, CDCl ) δ 147.5, 146.9, 142.3, 141.2, 137.7, 135.8,
32.1, 130.4, 130.1, 128.8, 128.7, 128.3, 128.2, 125.8, 123.5,
4
1
3
1
8
3
23.3, 121.2, 119.3, 109.1, 41.0, 29.5; IR (KBr) ν
= 1446, 1236,
max
+
87, 845, 751 cm− ; MS (ESI): m/z 619 (M + H) ; HRMS (ESI):
1
+
m/z calcd for C44
H N
35 4
(M + H) : 619.2856, found: 619.2850.
(
Table 4).
3
-Benzyl-6-bromo-9-methyl-4-phenyl-9H-pyrido[3,4-b]-indole (5)
To a stirred solution of 3-benzyl-9-methyl-4-phenyl-9H-pyrido
3,4-b]indole (4a, 50 mg 0.14 mmol), N,N-dimethylformamide
10 mL) was added to a round bottomed flask followed by slow
2
,6-Dibenzyl-7-phenyl-1-tosyl-1H-pyrrolo[3,2-c] pyridine (9a)
Following the general procedure, 7 (100 mg, 0.25 mmol) in
acetonitrile was allowed to react with 2a (64 mg, 0.30 mmol) in
the presence of pTSA (2.2 mg, 0.01 mmol) followed by the
[
(
addition of N-bromosuccinamide (30 mg, 0.17 mmol). The
reaction was carried out at room temperature for 12 hours,
and then water was added, followed by extraction with ethyl
acetate (2 times). The crude product was purified by column
chromatography on silica gel (EtOAc–hexane) to afford the
addition of NH OAc (23 mg, 0.30 mmol) to afford 5-azaindole
4
9
(
a in 80% yield (105 mg). Yellow solid, mp 180–182 °C, R
f
= 0.5
petroleum ether : EtOAc = 8 : 2); H NMR (500 MHz, CDCl
δ 8.67 (s, 1H), 7.34–7.27 (m, 3H), 7.20 (dd, J = 10.0, 4.3 Hz, 3H),
.13–7.03 (m, 5H), 7.00–6.92 (m, 6H), 6.81 (d, J = 6.8 Hz, 2H),
1
3
)
7
corresponding compound 5 in 85% yield (50 mg). Pale yellow
liquid, R
1
3
1
1
6.27 (s, 1H), 4.32 (s, 2H), 3.96 (s, 2H), 2.34 (s, 3H); C{ H}
NMR (125 MHz, CDCl ) δ 154.8, 145.8, 143.9, 143.6, 141.6,
1
1
IR (KBr): νmax = 3030, 1412, 1362, 1176, 1010, 749, 666 cm
MS (ESI): m/z 529 (M + H) ; HRMS (ESI): m/z calcd for
34 29 2 2
C H N O S (M + H) : 529.1944, found: 529.1931.
f
= 0.5 (petroleum ether : EtOAc = 1 : 1); H NMR
3
(400 MHz) δ 8.89 (s, 1H), 7.57–7.51 (m, 4H), 7.30–7.26 (m, 3H),
40.4, 137.9, 136.9, 136.4, 130.8, 129.5, 129.4, 128.7, 128.6,
27.9, 127.3, 126.9, 126.4, 125.7, 125.6, 110.7, 41.9, 36.6, 21.5;
7
7
3
1
1
.20–7.14 (m, 2H), 7.10 (ddd, J = 7.3, 3.7, 1.4 Hz, 1H),
.05–7.01 (m, 2H), 6.93 (t, J = 1.9 Hz, 1H), 4.18 (s, 2H), 3.93 (s,
H); C{ H} NMR (125 MHz, CDCl ) δ 147.6, 141.0, 140.7,
37.3, 135.8, 130.7, 130.6, 129.2, 128.9, 128.8, 128.2, 128.1,
27.0, 126.0, 125.7, 122.8, 112.0, 110.3, 40.6, 29.5; IR (KBr):
−
1
1
3
1
;
3
+
+
−
1
νmax = 1709, 1460, 1289, 1065, 753, 704 cm ; MS (ESI): m/z
2,6-Dibenzyl-7-(4-bromophenyl)-1-tosyl-1H-pyrrolo[3,2-c] pyridine
+
+
4
4
27 (M + H) ; HRMS (ESI): m/z calcd for C25
H
19BrN
2
(M + H) :
(
9b)
27.0810, found: 427.0847.
Following the general procedure, 7 (100 mg, 0.25 mmol) in
acetonitrile was allowed to react with 2d (88 mg, 0.31 mmol) in
the presence of pTSA (2.2 mg, 0.01 mmol) followed by the
3
-Benzyl-9-methyl-4-phenyl-9H-pyrido[3,4-b] indole 2-oxide (6)
To a stirred solution of 3-benzyl-9-methyl-4-phenyl-9H-pyrido
3,4-b] indole (4a, 50 mg, 0.143 mmol) in CHCl (10 mL) was
addition of NH OAc (23 mg, 0.30 mmol) to afford 5-azaindole
[
4
3
9
R
b in 86% yield (130 mg). Pale yellow solid, mp 180–182 °C,
added 70% m-CPBA (31 mg, 0.14 mmol), portion wise at 0 °C.
The mixture was stirred at room temperature for 12 h after the
completion of the reaction (monitored by TLC). The reaction
1
f
= 0.5 (petroleum ether : EtOAc = 8 : 2); H NMR (400 MHz,
CDCl ) δ 8.72 (s, 1H), 7.36–7.28 (m, 3H), 7.23 (dd, J = 7.6,
3
1
6
2
.7 Hz, 2H), 7.12–7.04 (m, 3H), 7.00 (dd, J = 8.1, 5.9 Hz, 4H),
mixture was diluted with CHCl
was added. The resulting mixture was stirred for an additional
0 min. The crude product was purified by column chromato-
3 2 3
, and solid K CO (4.0 equiv.)
.82–6.76 (m, 4H), 6.68 (d, J = 8.4 Hz, 2H), 6.40 (s, 1H), 4.38 (s,
1
3
1
H), 3.91 (s, 2H), 2.38 (s, 3H); C{ H} NMR (100 MHz, CDCl )
1
3
δ 154.4, 145.9, 143.9, 143.5, 141.9, 140.1, 137.9, 136.8, 135.1,
32.6, 130.0, 129.6, 129.3, 128.7, 128.5, 128.0, 126.9, 126.3,
125.7, 125.0, 121.9, 110.4, 41.9, 36.6, 21.5; IR (KBr): ν
graphy on silica gel (DCM : methanol) to afford the corres-
ponding compound 6 in 90% (46 mg). Pale yellow solid,
1
1
=
max
mp 108–110 °C, R = 0.5 (DCM : methanol = 9.5 : 0.5); H NMR
f
−
1
1
592, 1411, 1368, 1182, 997, 765, 702 cm ; MS (ESI): m/z 607
3
(400 MHz, CDCl ) δ 8.71 (s, 1H), 7.56–7.49 (m, 3H), 7.48–7.42
+
+
(
2 2
M + H) ; HRMS (ESI): m/z calcd for C34H28BrN O S (M + H) :
(m, 1H), 7.37 (d, J = 8.2 Hz, 1H), 7.32–7.28 (m, 2H), 7.20–7.12
607.1055, found: 607.1049.
(
1
m, 3H), 7.12–7.04 (m, 3H), 6.95 (t, 1H), 6.72 (d, J = 8.0 Hz,
H), 4.32 (s, 2H), 3.84 (s, 3H); C{ H} NMR (100 MHz, CDCl )
3
1
3
1
2
,6-Dibenzyl-7-phenylthieno[3,2-c] pyridine (10a)
δ 142.9, 141.0, 138.8, 136.5, 135.9, 133.2, 129.1, 129.0, 128.7,
1
3
28.3, 128.1, 127.6, 125.9, 122.4, 121.6, 121.3, 120.3, 108.8, Following the general procedure, 8 (100 mg, 0.39 mmol) in
−
1
3.3, 29.6; IR (KBr): νmax = 1225, 1162, 1003, 748, 701 cm
;
acetonitrile was allowed to react with 2a (99 mg, 0.47 mmol) in
+
MS (ESI): m/z 365 (M + H) ; HRMS (ESI): m/z calcd for the presence of pTSA (3.4 mg, 0.02 mmol) followed by the
C H N O (M + H) : 365.1661, found: 365.1656.
+
addition of NH OAc (36.6 mg, 0.47 mmol) to afford 5-azabenzo-
2
5
21
2
4
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Paper
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thiazole 10a in 96% yield (146 mg). Brown liquid, R
f
= 0.5 and PS thanks the University Grants Commission (UGC), New
1
(
petroleum ether : EtOAc = 7 : 3); H NMR (300 MHz, CDCl3) Delhi, for a fellowship. LG and SP thank the Department of
δ 8.91 (s, 1H), 7.43 (dd, J = 5.1, 1.8 Hz, 3H), 7.29 (dd, J = 6.8, Science and Technology and Inspire Faculty Programme. This
2
4
.6 Hz, 4H), 7.23 (d, J = 4.3 Hz, 2H), 7.14 (dd, J = 11.4, 6.3 Hz, research has been performed as part of the Indo-French “Joint
1
3
1
H), 7.00 (d, J = 6.7 Hz, 2H), 4.16 (s, 2H), 4.13 (s, 2H); C{ H} Laboratory for Natural Products and Synthesis towards
) δ 150.2, 149.9, 147.1, 143.3, 140.5, Affordable Health”. We thank the CSIR, CNRS and University
38.9, 137.7, 134.9, 130.6, 129.1, 128.7, 128.2, 128.1, 126.9, of Rennes 1 for their support.
NMR (100 MHz, CDCl
3
1
1
7
25.8, 120.0, 41.0, 37.0; IR (KBr): ν
= 3028, 1493, 1362, 1178,
max
61, 699, 671 cm− ; MS (ESI): m/z 392 (M + H) ; HRMS (ESI):
1
+
+
m/z calcd for C27
H
22NS (M + H) : 392.1467, found: 392.1488.
Notes and references
2
,6-Dibenzyl-7-(4-bromophenyl)thieno[3,2-c]pyridine (10b)
1
(a) G. W. Gribble and J. A. Joule, Progress in Heterocyclic
Chemistry, Elsevier, Oxford, 2008; (b) A. R. Katritzky,
C. A. Ramsden, E. F. V. Scriven and R. J. K. Taylor,
Comprehensive Heterocyclic Chemistry III, Pergamon, Oxford,
Following the general procedure, 8 (100 mg, 0.39 mmol) in
acetonitrile was allowed to react with 2a (135 mg, 0.47 mmol)
in the presence of pTSA (3.4 mg, 0.02 mmol) followed by the
addition of NH
zothiazole 10b in 90% yield (171 mg). Brown liquid, R
(
4
OAc (36.6 mg, 0.47 mmol) to afford 5-azaben-
= 0.5
petroleum ether : EtOAc = 8 : 2); H NMR (500 MHz, CDCl3)
δ 8.91 (s, 1H), 7.57–7.53 (m, 2H), 7.30 (d, J = 7.4 Hz, 2H),
2008; (c) A. R. Katritzky, C. W. Rees, E. F. V. Scriven and
f
1
A. McKillop, Comprehensive Heterocyclic Chemistry II,
Pergamon, Oxford, 1996; (d) T. Eicher and S. Hauptmann,
The Chemistry of Heterocycles, Wiley-VCH, Weinheim, 2003;
7
4
.25–7.21 (m, 3H), 7.18–7.11 (m, 6H), 6.99 (d, J = 7.2 Hz, 2H),
1
3
1
(
e) A. P. Rajput and A. R. Kankhare, Synthetic utility of aza-
heterocyclics: A Short Review, Int. J. Pharm. Sci. Invent.,
017, 6, 19–25.
.16 (s, 2H), 4.11 (s, 2H); C{ H} NMR (100 MHz, CDCl )
3
δ 150.1, 147.3, 143.6, 140.2, 138.8, 136.5, 135.0, 132.0, 130.8,
2
1
4
6
29.4, 128.8, 128.7, 128.6, 128.2, 127.0, 125.9, 122.5, 120.0,
2
3
4
(a) H. Guan, H. Chen, W. Peng, Y. Ma, R. Cao, X. Liu and
A. Xu, Eur. J. Med. Chem., 2006, 41, 1167–1179;
1.0, 37.0; IR (KBr): ν
= 3026, 1488, 1436, 1078, 1011, 749,
max
99 cm− ; MS (ESI): m/z 470 (M + H) ; HRMS (ESI): m/z calcd
1
+
+
(
b) L. P. P. Liew, J. M. Fleming, A. Longeon, E. Mouray,
for C H BrNS (M + H) : 470.0578, found: 470.0560.
2
7
21
I. Florent, M. L. B. Kondracki and B. R. Coop, Tetrahedron,
2014, 70, 4910–4920; (c) R. Cao, W. Peng, Z. Wang and
A. Xu, Curr. Med. Chem., 2007, 14, 479–500; (d) L. Guo,
W. Chen, R. Cao, W. Fan, Q. Ma, J. Zhang and B. Dai,
Eur. J. Med. Chem., 2018, 147, 253.
UV-visible, emission and lifetime studies
Electronic absorption spectra were recorded using a Shimadzu
(model UV-3600) spectrophotometer. Steady-state fluorescence
spectra of β-carboline were recorded using a Fluorolog-3 spec-
trofluorometer (SPEX model, Jobin Yvon) at wavelengths of
excitation (λexc) = 290 and 365 nm. Fluorescence lifetime
measurements were measured on a picosecond time correlated
single-photon counting (TCSPC) setup (Fluorolog 3-Triple
Illuminator, IBH Horiba Jobin Yvon) employing a picosecond
light-emitting diode laser (NanoLED, λexc = 301 nm).
(a) D. Singh, S. Devi, V. Kumar, C. C. Malakar, S. Mehra,
S. Rattan, R. K. Rawald and V. Singh, Org. Biomol. Chem.,
2
016, 14, 8154; (b) T. Herraiz, D. Gonzalez, C. Ancín-
Azpilicueta, V. J. Aran and H. Guillen, Food Chem.
Toxicol., 2010, 48, 839; (c) B. Pohl, T. Luchterhandt and
F. Bracher, Synth. Commun., 2007, 37, 1273;
(
d) J. D. Panarese and S. P. Waters, Org. Lett., 2010, 12,
Electrochemical studies
4086.
(a) G. Dominguez and P. J. Castells, Eur. J. Org. Chem.,
CV experiments were performed on a PC-controlled CH instru-
2
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