C-H functionalization of azines. Anodic dehydroaromatization of 9-(hetero)aryl-9,10-dihydroacridines

Article abstract of DOI:10.1039/c6ra17783b

Data on anodic dehydroaromatization of 9,10-dihydroacridines, bearing aryl and heteroaryl fragments, are presented. Effects of both electron-donating and electron-withdrawing substituents on the current-voltage characteristics of these compounds have been established. The experimental data proved to be in a good agreement with quantum chemical calculations. A simple and convenient method for the electrochemical conversion of dihydroacridines into the corresponding 9-(hetero)aryl-N-methylacridinium salts has been advanced.

Full text of DOI:10.1039/c6ra17783b

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C-H Functionalization of azines. Anodic dehydroaromatization of
9-(hetero)aryl-9,10-dihydroacridines
A. V. Shchepochkin,a,b O. N. Chupakhin,a,b V. N. Charushin,a,b D. V. Steglenko,c V. I. Minkin,c G. L.
Rusinova,b and A. I. Maternb
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
The data on anodic dehydroaromatization of 9,10-dihydroacridines, bearing aryl and heteroaryl fragments, are presented.
Effects of both electron-donating and electron-withdrawing substituents on the current-voltage characteristics of these
compounds have been established. The experimental data proved to be in a good agreement with quantum chemical
www.rsc.org/
calculations.
A
simple and convenient method for the electrochemical conversion of dihydroacridines into the
9-(hetero)aryl-N-methylacridinium salts has been advanced.
corresponding
use of such methods. At the same time, there are direct reac-
H
tions of nucleophilic aromatic substitution of hydrogen (SN
Introduction
Ar), that require neither metal complex catalysts, nor the
presence of a halogen or other leaving groups.9 The first step
Acridines belong to an important class of heteroaromatic
compounds, which are widely used in photo-redox catalysis,
molecular machines, sensors and transistors.1 Arylacridines
appear to be particularly attractive compounds due to their
diverse biological activity.2 Indeed, a whole number of acri-
dines, exhibiting antitumor, antiviral, antimalarial, antiprion
and analgesic properties have recently been revealed.3 Im-
portantly, that 9-aryl-substituted acridines are considered to
be the most convenient models to study the hydride transfer
reactions, proceeding with participation of the NAD+ coen-
zyme.4
H
in the SN reactions involves a nucleophilic attack at C-H car-
bon of an aromatic ring, thus leading to the intermediate ϭH-
adduct. The next step is oxidative aromatization of this inter-
mediate, accompanied by the loss of proton and a pair of elec-
trons, formally of the hydride-ion (Scheme 1). It happens very
H
often that the SN reactions are carried out as three-
component syntheses, i.e., an oxidant is injected into the reac-
tion system together with the reaction partners. When consid-
ering susceptibility of reagents to oxidative process, the behav-
ior of nucleophiles has first to be considered, although oxida-
tive transformations of the starting aromatic substrates and
There are three main approaches to obtain 9-arylacridines. The
first one suggests construction of the acridine tricyclic system,
and it is based on condensation of the corresponding arylcar-
boxylic acid with diphenylamine in the presence of zinc chlo-
ride at temperatures 200-260 oC.5 The second method, exploit-
ing cross-coupling reactions, is associated with the necessity of
incorporation of good leaving groups into acridines and use of
metal catalysts.6 Transition metal-catalyzed cross-coupling
reactions are also used for the direct functionalization of C-H-
bonds in acridines.7 This method avoids use of halides; howev-
er, it does not eliminate all problems inherent for the metal-
catalyzed reactions, including the formation of by-products
with organometallic reagents, homo-coupling reactions and
difficulties in removal of catalysts and auxiliary ligands from
reaction mixtures.8 All these features impose restrictions on
H
SN products are also possible. Therefore, choice of a suitable
H
oxidant is the crucial factor to realize the SN transformations.
In spite of a considerable progress in studying of this type re-
actions, there are still no clear criteria for selection of an ap-
propriate oxidant, and chemists have to settle themselves with
experience, intuition and some empirical rules.9,10
Nu
H
H
Nu
[O]
ꢀ2eꢀ ꢀH+
Nu-
ꢀ
+
W
W
W
бHꢀadduct
Wꢀ electron withdrawing group
Scheme 1. Nucleophilic aromatic substitution of hydrogen
a.Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences, S.
Kovalevskaya Str., 22, Ekaterinburg, 620041, Russia.
In this respect, use of electrochemical methods appears to be
a very attractive approach.11 Besides development of the at-
om-economical version of the oxidative reactions, electro-
chemical methods provide an opportunity to get insight into
the reaction mechanism, thus making a choice of chemical
oxidant to be a more rational one.12,13 However, analysis of the
b.Ural Federal University, Mira St. 19, Ekaterinburg, 620002, Russia.
c. Institute of Physical and Organic Chemistry, Southern Federal University, Stachki
Av., 194/2, Rostov on Don, 344090, Russia.
† Footnotes relaꢀng to the ꢀtle and/or authors should appear here.
Electronic Supplementary Information (ESI) available: [details of any supplemen-
tary information available should be included here]. See DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
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literature data shows that electrochemical methods have long lowed by quaternization, and reduction with NaBH4 (Scheme
been neglected, until a series of papers dedicated to electro- 3). The cross-coupling products 6o-q have been prepared by
chemical SNH reactions of nitroarenes with a variety of nucleo- reacting chloroacridine
4 with boronic acids in the presence of
philes of different nature (C, N, O, P-centered) have been pub- 5% Pd(PPh3)4 and 2.5 equiv. of K2CO3 in dioxane - water (1:4)
lished.13 As far as electrochemical conversions of heterocyclic solution at 165 oC under microwave irradiation. Quaternization
ϭH-adducts are concerned, these examples are very rare, espe- of 6o
,p has been performed with an excess of methyl iodide in
cially those arranged in the preparative mode.14 As for dihy- diethyl ether at room temperature. In case of 6q quaterniza-
droacridines, the data on their preparative electrochemical tion was carried out in refluxing dimethyl sulfate. The precipi-
dehydroaromatization have not so far been available in the tates obtained were treated with NaBH4 in boiling ethanol to
literature.
give the corresponding dihydroacridines 2o-q.
In this communication we wish to report the synthesis of the The behavior of ϭH-adducts 2a-q was studied by cyclic voltam-
series of 9-(hetero)aryl-9,10-dihydroacridines, to describe metry in anhydrous acetonitrile under argon (in the presence
electrochemical method of their aromatization, and finally, to of NH4BF4) with a scan rate of 100 mV/s. All compounds
discuss correlations between DFT calculations and current- proved to be characterized by well-defined peaks of irreversi-
voltage characteristics.
ble two-electron oxidations (Figure 1). Values of oxidation po-
tentials are given in Table 1.
The data of voltammetry studies show that oxidative poten-
tials of compounds tested are quite sensitive to electronic ef-
fects of aryl substituents at C-9 of 9,10-dihydroacridines. As
expected, introduction of a strong electron-donating substitu-
ent, such as 4-NH2 (compound 2c), decreases oxidation poten-
tial of 100 mV relative to unsubstituted analogue 2a; also 4-
N(Et)2 group in 2d proved to reduce the potential by 200 mV.
In contrast, the transfer from compound 2d to 2g, bearing pa-
ra-F substituent, enhances the oxidation potential of the latter
up to 330 mV (130 mV relative to dihydroacridine 2a).
Results and discussion
In order to obtain quantitative data on dehydroaromatization
of azines, and to estimate effects of both electronic and steric
factors on oxidation of these compounds, a series of 10-
methyl-9-aryl substituted dihydroacridines have been synthe-
sized (2a-q) (Table 1).
Dihydroacridines 2a,b,g,h,m have been prepared through the
reaction of 10-methylacridinium iodide with the corresponding
magnesium aryl bromides. Compounds 2i-l are derived from
the reaction of the 10-methylacridinium ion with sodium phe-
nolates in diethyl ether at room temperature. Arylamines
proved to react directly in DMSO with the acridinium cation to
form aminocompounds 2c and 2d 15
. Carbamoyl derivatives 2e
and 2f were obtained by treatment of the amino compound 2c
with the corresponding anhydrides. Compound 2n was pre-
pared by reacting the lithium derivative of furan with acridine
1
(Scheme 2).
H
Nu
H
Nu-
Figure 1. Cyclic voltammogram of 2m, 10-3 M in CH3CN, using a platinum disk electrode
(2 mm diameter), supporting electrolyte NH4BF4 10-1M; scan rate 100 mV/s; reference
electrode Ag/AgNO3
N+
CH3
1
N
I
CH3
2a-n
2a,b,g,h,m
It could be anticipated that introduction of electron-
withdrawing substituents, such as CN and CF3 (compounds 2o
and 2p), would increase significantly their oxidation potentials.
However, the results of voltammetry measurements of these
compounds have shown that oxidative potentials are practical-
ly unchanged, being at the level of unsubstituted compound
2a. The presence of para-NO2 group in compound 2q enhances
the oxidative potential by only 60 mV. This surprising fact can
possibly be explained by the difference in geometrical configu-
rations of compounds, bearing electron-donating (2c) and
electron-withdrawing (2p) substituents.
(Het)ArMgBr
Arylamines
Li
O
2n
2c,d
1
Sodium Phenolates
2i-l
Anhydrides
2e,f
2c
Scheme 2. Synthesis of dihydroacridines 2a-n
To test this hypothesis, X-ray diffraction studies of single crys-
tals of compounds 2a, 2c, 2p have been carried out. A general
Dihydroacridines 2o-q, bearing electron-withdrawing substitu-
ents, which cannot be obtained by the methods described
above, were prepared through the Pd-catalyzed cross-coupling
view of these molecules and adopted numbering of atoms are
given in Figure 2. According to the X-ray structural analysis
(XRS) data, all compounds studied are crystallized in the cen-
reaction of 9-chloroacridine
4 with boronic acids 5o-q, fol-
2 | J. Name., 2012, 00, 1-3
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trosymmetric groups of the space symmetry. The molecular lated HOMO energies (Table 1) and the experimentally ob-
packing of these compounds is nonspecific, no significant trun- tained oxidation potentials has revealed the following general
cation of contacts has been observed. Conformation of the trend: the lower values of Epa, the higher values of EHOMO
.
central dihydropyridine ring in these compounds may be char- The visual representation of HOMO for dihydroacridines
acterised as the pseudo-boat with the emerging plane of C(7) demonstrates clearly the electronic effects of substituents. For
and N(1), and the axially extending substituent. In the test ex- all compounds bearing electron-withdrawing substituents, the
periment the dihydropyridine fragment exhibits a flexion along HOMO orbitals are localized on the acridine fragment of the
the axis N(1)-C(7) in such a way, that the dihedral angle be- molecules. This explains a low impact of electron-withdrawing
tween the benzene rings achieves a substantial value (37.13o substituents. As for dihydroacridines, bearing electron-
for compound 2p, 35.24o for 2a, 23.42o – 2c). Bond lengths are donating groups (compounds 2c and 2d), the latter are also
in a good agreement with the standard values; length devia- involved in the HOMO electron density distribution, thus ex-
tions are not exceeding 0.01 Å relative to the mean value. The plaining a decrease in oxidation potentials for these structures
nitrogen configuration in the pyridine ring is approximately (Figure 3).
planar: sums of CNC angles are equal to 358.0(3)o for 2c, It should be noted that the observed values Epa are in good
355.2(3)o – for 2a, and 355.8(3)o – for 2p. Therefore, in all cas- agreement with constants ϭR, which reflect resonance effects
es N-atoms appear to have the sp2-configuration, and are of substituents,16 expressed in ϭR values:
strongly conjugated with the benzene rings. In spite of a low-
temperature used in the x-ray experiment for 2p, CF3-groups
of the Ph-substituent show a strong disordering. No shortened
intermolecular contacts in this packing have been observed.
Thus, the x-ray data demonstrate a close similarity in geometry
of the tested compounds, and no significant differences be-
tween their structures have been observed.
R
NEt2
NH2
OMe
Me
F
CN
CF3
NO2
ϭR -0.57 -0.51 -0.43 -0.08 -0.48 0.08 0.08 0.15
These data show that oxidation potentials are depending
mainly on substituents with a positive mesomeric effect (+M).
Indeed, the compound 2g, bearing para-F substituent (+M; -I)
has a higher oxidation potential. Introduction of electron-
withdrawing substituents, such as CN, CF3 and NO2 (-M; -I), has
practically no effect on their oxidation potentials.
The DFT calculations of HOMO orbitals, directly involved in the
oxidation process, have been performed. Analysis of the calcu-
R
R
R
Pd(PPh3)4
Cl
R
K2CO3
NaBH4
EtOH
MeI
H
+
or
MW, 170 o
C
N
4
Me2SO4
X
N+
N
N
5o-q
CH3
CH3
6o-q
2o-q
o: R=CN, X=boronic acid pinacol ester; p: R=CF 3, X=B(OH)2; q: R=NO2, X=B(OH)2
Scheme 3. Synthesis of dihydroacridines 2o-q
Figure 2. X-ray structures of 2a, 2c, 2p.
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Table 1. Results of electrochemical studies and quantum chemical calculations obtained in the approximation of B3LYP/6-311+G (3df, 2p)
Yields of
Yields of
H
H
Compound
Epa (V) ϭH-
the SN
products 3
(%)
Compound
Epa (V) ϭH-
the SN
Nu
-Ph
EHOMO (eV)
-5,476
Nu
EHOMO (eV)
2
adducts 2
2
adducts 2
products 3
(%)
a
b
0,68
0,70
88
-C6H4-CH3-p
-5,451
92
91
j
0,64
0,68
-5,231
-5,418
87
87
OH
OH
c
-C6H4-NH2-p
-C6H4-NEt2-p
0,58
0,48
-5,389
-5,110
k
OH
H3C
CH3
d
85
l
0,65
-5,330
90
H
N
CF3
e
f
0,69
0,66
-5,680
-5,625
85
86
m
n
0,70
0,70
-5,498
-5,446
95
91
O
S
H
N
CH3
O
O
g
-C6H4-F-p
0,81
0,68
-5,573
-5,349
97
91
o
p
-C6H4-CN-p
-C6H4-CF3-p
0,68
0,70
-5,766
-5,590
89
92
h
-C6H4-OCH3-p
i
0,57
-5,232
92
q
-C6H4-NO2-p
0,74
-5,664
94
OH
Figure 3. Visual representation of the HOMO obtained in the approximation of B3LYP/6-311+G (3df, 2p) for compounds 2a, 2c, 2d, 2g, 2o, 2p
4 | J. Name., 2012, 00, 1-3
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In summary, oxidation potentials of dihydroacridines 2a-q are Preparative electrolyses were carried out using Autolab
in the range of 0,48-0,81 V. However, most of compounds PGSTAT128N in 50-mL three-electrode cell. The working sur-
have the potentials close to 0,70 V, while introduction of elec- face of the platinum wire anode used as a working electrode
tron-withdrawing substituents have no effect on values of oxi- was 15.0 cm2. A tracing-paper was used as a membrane. A
dation potentials. Only the presence of electron-donating sub- platinum wire served as a cathode, and the catholyte was a
stituents leads to lower values of oxidation potentials. Ob- saturated solution of the background used in the catholyte in
tained data can serve as a guide in the selection of the chemi- the corresponding solvent.
cal oxidizing agent in SNH reactions at least in the series of acri- 1H and 13C NMR spectra were recorded on a AVANCE-500 in-
dines.
struments using Me4Si as an internal standard. Elemental anal-
Taking into account the data, obtained by cyclic voltammetry, ysis was carried on a Eurovector EA 3000 automated analyzer.
the ϭH-adducts have been subjected to preparative electro- Melting points were determined on Boetius combined heating
oxidation (Scheme 4).
stages and were not corrected.
The GC-MS analysis of all samples was carried out using an
Agilent GC 7890A MS 5975C Inert XL EI/CI GC-MS spectrometer
with a quadrupole mass-spectrometric detector with electron
ionization (70 eV) and scan over the total ionic current in the
range m/z 20–1000 and a quartz capillary column HP-5MS (30
m × 0.25 mm, film thickness 0.25 mm). Helium served as a
carrier gas, the split ratio of the flow 1:50, and consumption
through the column 1.0 mL min–1; the initial temperature of
the column 40 °C (storage 3 min), programming rate 10 °C
min–1 to 290 °C (storage 20 min), the temperature of the evap-
orator 250 °C, the temperature of the source 230 °C, the tem-
perature of the quadrupole 150 °C, and the temperature of the
transition chamber 280 °C. Solutions of samples with concen-
tration of 3–4 mg mL–1 were prepared in toluene. Samples of 1
mL of the obtained solutions were analyzed.
Nu
Nu
H
Anode
ꢀ2eꢀ
H2
NH3
+
+
NH4BF4
CH3CN
N
N+
ꢀ
CH3
CH3 BF4
3 a-q
2 a-q
Scheme 4. Synthesis of acridinium tetrafluoroborates 3a-q
Electrolysis was carried out under argon, using 0.1M solution
NH4BF4 in CH3CN-CH3OH (5:1), as the supporting electrolyte.
The electrolyte, containing 2 mmol of ϭH-adduct, was placed in
an anode compartment of the cell, the electrodes of which
were separated by a membrane of tracing paper. Electrolysis
at the controlled potential (the reference electrode Ag/AgNO3;
2.1 F/mol) leads to the loss of two electrons and a proton, thus
resulting in the formation of aromatic SNH products 3a-q (Table
1).
Microwave experiments were carried out in a Discover uni-
modal microwave system (CEM, USA) with a working frequen-
cy of 2.45 GHz and the power of microwave radiation ranged
from 0 to 300 W. The reactions were carried out in a 10 mL
reaction tube with hermetic Teflon cork. The temperature of
the reaction was monitored using an inserted IR sensor for the
external surface of the reaction vessel.
The reaction proceeds selectively, without any by-products,
thus providing high yields of the target compounds (from 85 to
95%). Selection of NH4BF4 as electrolyte was due to its suffi-
cient stability in the range of studied potentials and good re-
sults of the electrolysis. In fact, oxidation in NaClO4 or NaBF4
media failed, (yields were not exceeding 25%), while the pres-
ence of tetraalkylammonium salts proved to complicate signif-
icantly isolation of the target products.
XRD experiments were carried out on an automated diffrac-
tometer “Xcalibur S” with CCD detector on standard procedure
(graphite monochromated Mo-Kα radiation with λ = 0.71069 Å,
ω-scanning with step 1o). The unit cell parameters were re-
fined using all collected spots after the integration process.
The data were not corrected for absorption.
Experimental
The structure 3n was solved by direct methods with SHELX97
program package.18 The structures 2а
, 2c and 2p were solved
General Information
using Olex219 with the Superflip20 structure solution program
by Charge Flipping. All the structures were refined by full-
matrix least squares on F2 using ShelXL97. All the non-
hydrogen atoms were refined with anisotropic temperature
factors. The H-atoms at the C(sp3)-atoms in the dihydroazine
rings were solved and refined independently in isotropic ap-
proximation. All other H-atoms were calculated with AFIX and
were included in the refinement at “riding” model with a
common isotropic temperature factor. Deposition numbers
CCDC 1479455 for 3n, CCDC 1479454 for 2а, CCDC 1479456 for
2c, CCDC 1479453 for 2p contain the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from the Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
All starting reagents and solvents were obtained from com-
mercial sources and dried by standard procedures before use.
10-Methylacridinium iodide was synthesized according to the
known procedure.17
Cyclic voltammograms were recorded by an Autolab
PGSTAT128N instrument. The experiments were carried out
under argon in anhydrous acetonitrile with the additives of
supporting electrolyte NH4BF4 (0.1 mol/L) at 17-18 °C in a
three-electrode system. A platinum disk electrode (d=2 mm)
used as a working electrode, a glass graphite rod as an auxilia-
ry electrode, Ag/AgNO3 was a reference electrode. The scan-
ning rate was set 100 mV/s. The concentration of the samples
was arbitrary.
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IR spectra of samples (solid powders) were recorded on a solved in 10 mL of hot ethanol. To the stirred solution was
Spectrum One Fourier transform IR spectrometer (Perkin added 37.83 mg (1 mmol) NaBH4. The solid was filtered off
Elmer) equipped with a diffuse reflectance attachment (DRA). after cooling. Nitrophenyl acridine 6q (1 mmol) was suspended
Spectrum processing and band intensity determination were in 3 mL of dimethyl sulfate and heated for 6 hours, after that it
carried out using the special software supplied with the spec- was cooled and poured into 30 mL of ether. The solid was fil-
trometer.
tered, dissolved in 10 mL of hot ethanol and treated with
NaBH4.
Synthesis of 9,10-dihydroacridines
General procedure for the Synthesis of 2a,21 2b, 2g, 2h,22 2m. The-
se compounds were prepared through the addition of the Gri-
gnard reagents to 10-methylacridinium iodide. Aryl Grignard
reagents were prepared from the corresponding aryl bromides
(3,74 mmol) and magnesium (89,8 mg, 3,74 mmol) in 20 mL of
anhydrous ether. An ether solution of the Grignard reagent
was transferred to flask containing a stirred suspension of 10-
methylacridinium iodide (1.0 g, 3.12 mmol) in 20 mL of anhy-
drous ether. The stirring was continued until the red, ether-
insoluble acridinium iodide was entirely consumed. 5 ML of
methanol was added to destroy unreacted Grignard reagent. A
white precipitate of magnesium salts was removed by filtra-
tion, and the solvent was evaporated under reduced pressure
to give solid materials which were recrystallized from ethanol.
General procedure for the Synthesis of 2i-l. These compounds
were prepared by addition of the corresponding phenolates to
10-methylacridinium iodide. Phenolates were prepared from
phenols (3,74 mmol) and sodium (85.98 mg, 3,74 mmol) in 20
mL of anhydrous ether. An ether solution of the corresponding
phenolate was transferred to a flask, containing a stirred sus-
pension of 10-methylacridinium iodide (1.0 g, 3.12 mmol) in 20
mL of anhydrous ether. The stirring was continued until the
red, ether - insoluble acridinium iodide was entirely consumed.
The solvent was removed by evaporation under reduced pres-
sure to give a pale yellow solid, which was recrystallized from
ethanol.
Synthesis of 2n. To a Schlenk flask with 0.27 mL (3.75 mmol)
furan 10 mL of ether were added. The solution was cooled
down to -78°C for 15 min and hexane solution of n-butyl lithi-
um (1.6M, 2.34 mL, 3.75 mmol) were added. The solution was
allowed to warm up to 0°C for 30 min, resulting in the for-
mation of the furyllithium. The ether solution of lithium inter-
mediate was transferred to flask containing a stirred suspen-
sion of 10-methylacridinium iodide (1.0 g, 3.12 mmol) in 20 mL
of anhydrous ether. The stirring was continued until the red,
ether - insoluble acridinium iodide was entirely consumed. 5
ML of methanol was added to destroy unreacted lithium rea-
gent, and the solvent was removed by evaporation under re-
duced pressure, to give a pale yellow solid, which was recrys-
tallized from ethanol.
General Procedure for the electrochemical oxidation of ϭH-
adducts 2a-q. Electrolysis was carried out in a stream of argon
using a 0.1 M NH4BF4 solution in a CH3CN–CH3OH (5:1) mixture
as the supporting electrolyte, in a temperature-controlled (20
°C). The supporting electrolyte (50 mL) containing 2 mmol ϭH-
adduct 2a-q of was placed in the anode cell compartment and
the supporting electrolyte (10 mL) was placed in the cathode
compartment. Electrolysis was carried out at a controlled po-
tential (reference electrode Ag/AgNO3). Upon passing 2.1F of
electricity (for a two-electron process), the electrolysis was
stopped, the solvent was distilled off in vacuum from the
anolyte, the residue was washed with ether. The residue was
recrystallized from water and dried on air.
Synthesis of 2c, 2d. These compounds were synthesized ac-
cording to the published procedures.15
Synthesis of 2e, 2f. To
a solution of 10-methyl-9-(4-
aminophenyl)-9,10-dihydroacridine 2c (286 mg, 1mmol) in 5
mL acetonitrile 1,05 mmol the corresponding anhydride was
added. After 10 minutes solvent was distilled off under a re-
duced pressure, and the residue was recrystallized from etha-
nol.
Conclusions
A convenient, simple and highly selective method for electro-
chemical conversion of dihydroacridines into the correspond-
ing 9-arylacridines has been advanced. This method is based
on using the electric energy, requires no external oxidant, pro-
vides high yields of the target products and corresponds to the
principles of green chemistry.23
General procedure for the microwave-assisted palladium
catalyzed cross-coupling reactions for synthesis 6o-q. 9-
Chloroacridine
4 (100 mg, 0.47 mmol), the corresponding phe-
Experimental and calculation data concerning anodic dehy-
droaromatization of a variety of 9,10-dihydroacridines, bearing
aryl and hetaryl fragments with electron-donating or electron-
withdrawing substituents have been obtained. It has been
demonstrated that introduction of electron-donating substitu-
ents results in a substantial decrease of oxidation potentials,
while electron-withdrawing groups have a minimal effect.
nylboronic acid (5o-q) (0.564 mmol), Pd(PPh3)4 (27 mg, 0.023
mmol) and K2CO3 (162 mg, 1.17 mmol) were dissolved in 4 mL
dioxane and 1 mL water. The resulting mixture was deaerated
by bubbling argon and irradiated in a microwave apparatus at
165 °C (250 W) for 15 min. After that solvent was distilled off
under a reduced pressure, and the residue was washed with
30 mL methylene chloride. The organic solvent was distilled off
under reduced pressure, the residue was recrystallized from
ethanol.
Acknowledgements
Synthesis of 2o-q. To a solution of compound 6o or 6p (1
mmol) in 10 mL of diethyl ether 0.3 mL of methyl iodide was
added. After 24 hours the precipitate was filtered and dis-
The research was financially supported by the Russian Science
Foundation (Project No. 14-13-01177).
6 | J. Name., 2012, 00, 1-3
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DOI: 10.1039/C6RA17783B
Journal Name
ARTICLE
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Steglenko D.V. and Minkin V.I. would like to thank the South-
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RSC Advances
Page 8 of 8
A simple and efficient electrochemical method for the oxidative
conversion of dihydroacridines into the corresponding 9-
(hetero)aryl-N-methylacridinium salts has been developed.
Current-voltage characteristic of dihydroacridines are given.
View Article Online
DOI: 10.1039/C6RA17783B
Nu
Nu
H
17 examples
up to 87% yield
N+
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CH3
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+
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