Electrochemical Oxidative Aromatizationof 9-Substituted 9,10-Dihydroacridines: Cleavage of C–H vs C–X Bond

Article abstract of DOI:10.1007/s10593-019-02562-x

[Figure not available: see fulltext.] Reactivity of dihydroacridines bearing a С–X fragment at the geminal C-9 atom (where X = C, N, O, P, S) on anode has been investigated by means of electrochemical oxidation and thermodynamic and quantum-chemical calculations. The electrochemical oxidation results either in the formation of the 9-substituted acridines or in the cleavage of the C–X bond. This dual behavior of dihydroazines is analogous to processes reported in literature that take place upon treatment with chemical oxidants.

Full text of DOI:10.1007/s10593-019-02562-x

DOI 10.1007/s10593-019-02562-x
Chemistry of Heterocyclic Compounds 2019, 55(10), 956–963
Electrochemical oxidative aromatization
of 9-substituted 9,10-dihydroacridines:
cleavage of C–H vs C–X bond
Oleg N. Chupakhin1,2*, Alexander V. Shchepochkin1,2, Valery N. Charushin1,2,
Anna V. Maiorova2,3, Tatyana V. Kulikova2,3, Konstantin Yu. Shunyaev2,3,
Andrey N. Enyashin4, Pavel A. Slepukhin1,2, Anna I. Suvorova2
1 Postovsky Institute of Organic Synthesis, Russian Academy of Sciences,
20 Akademicheskaya / 22 S. Kovalevskoi St., Yekaterinburg 620990, Russia;
е-mail: chupakhin@ios.uran.ru
2 Ural Federal University named after the first President of Russia B. N. Yeltsin,
19 Mira St., Yekaterinburg 620002, Russia; е-mail: avs@ios.uran.ru
3 Institute of Metallurgy, Ural Branch of the Russian Academy of Sciences,
101 Amundsena St., Yekaterinburg 620016, Russia; е-mail: shun@imet.mplik.ru
4 Institute of Solid State Chemistry, Ural Branch of the Russian Academy of Sciences,
91 Pervomaiskaya St., Yekaterinburg 620990, Russia; е-mail: enyashin@ihim.uran.ru
Submitted April, 12, 2019
Accepted after revision July 3, 2019
Published in Khimiya Geterotsiklicheskikh Soedinenii,
2019, 55(10), 956–963
Reactivity of dihydroacridines bearing a С–X fragment at the geminal C-9 atom (where X = C, N, O, P, S) on anode has been
investigated by means of electrochemical oxidation and thermodynamic and quantum-chemical calculations. The electrochemical
oxidation results either in the formation of the 9-substituted acridines or in the cleavage of the C–X bond. This dual behavior of
dihydroazines is analogous to processes reported in literature that take place upon treatment with chemical oxidants.
H
Keywords: acridines, dihydroacridines, bond dissociation energy, C–H functionalization, electrochemical oxidation, SN reactions,
thermodynamic studies.
Nitrogen-containing heteroaromatic ring systems are
building blocks for a wide range of compounds with pharma-
ceutical and technical applications.1,2 Acridines, a class of
nitrogen heterocycles, are actively used as photoredox
catalysts,3 molecular machines,4 sensors,5 and transistors.6
Besides, acridine derivatives are especially attractive due to
their various biological activity.7,8 Inhibitors of acetyl-
cholinesterase,9 substances with antitumor,10,11 antiviral,12
antimalarial,13 antiprion,14 analgesic15 properties have recently
been found among these compounds. Importantly, the 9-sub-
stituted acridines are applied as NAD+ coenzyme models
for the study of hydride transfer reaction.16,17 However,
effective methods of their functionalization are limited and
usually based on cross-coupling reactions with transition
metals.18,19 The most common ways of the synthesis of
9-substituted acridines are still the methods of building the
acridine scaffold from prefunctionalized ring systems20–23 and
substituting easily leaving groups, mainly chlorine.24
At the same time there are methods of direct C–H
functionalization without metallocatalysis, including
reactions of the nucleophilic aromatic substitution of
hydrogen (SNHAr reactions).25–29 According to the generally
accepted mechanism of the SNHAr reactions, these
processes take place following a two-stage scheme. In the
first stage, electron-rich compound (nucleophile X–)
interacts with electron-deficient aromatic substrate I, most
often in a reversible way, which results in the formation of
the intermediate II, the so-called σH-adduct. The oxidative
aromatization of the σH-adduct II with the formal
elimination of hydride ion (H– = 2e– + H+) is taking place
in the second stage using an oxidizing agent which can be
either the initial substrate I or an external oxidant (Scheme 1).
0009-3122/19/55(10)-0956©2019 Springer Science+Business Media, LLC
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Chemistry of Heterocyclic Compounds 2019, 55(9), 956–963
Scheme 1
Studies show that the oxidation stage consists of
formation of C–C bonds and only about 12% to C–N
bonds. The remaining 18% of publications are associated
with the formation of C–O, C–S, C–P, and C–Si bonds. It
is not excluded that a noticeably smaller share of the
products of C–X substitution in comparison with the
products of C–C coupling can be explained by the decay of
σH-adducts to the initial compounds.33 In general, the
direction of the process depends on the nature of the
nucleophile: in the case of C-nucleophiles, the cleavage of
C–H bond is observed, while for heteroatom (N, S, P, O)
nucleophiles the cleavage of C–X bond is more often
encountered.
One can assume that the observed patterns in the
behavior of σH-adducts are of a similar nature, and attempts
to investigate, explain, and predict the direction of aroma-
tization can have a general character for the chemistry
of arenes and heteroarenes. So far, such work has been
carried out only on the example of nitroarenes.32 On the
other hand, there have been no similar studies in respect to
the heterocyclic σH-adducts of type II, although they are
much more convenient due to the higher stability, in some
cases even with the possibility of carrying out X-ray
diffraction analysis.34
The present paper is devoted to the study of the electro-
chemical oxidative aromatization of dihydroacridines with
a С–X fragment at the geminal C-9 atom (where X = C, N,
O, P, S) and the identification of a general pattern for the
direction of the above process, using X-ray diffraction,
thermodynamic and quantum-chemical calculations, also
taking into account the possibility of decay of the radical
intermediates III (Scheme 1). Previously,35,36 we have
developed methods of the direct C–H functionalization of
the N-methylacridinium cations using C-, N-, S-, P-, and
O-nucleophiles, which allowed to afford a wide range of
σH-adducts 1–34 (Fig. 1).
elementary acts of electron transfer with the formation of
the radical species III and further oxidative aromatization
by removal of a proton and an electron, which is equivalent
to elimination of a hydride ion. However, the reaction can
proceed along a different pathway with the cleavage of C–X
bond and the elimination of the nucleophilic fragment as a
radical (Scheme 1).30–32
Questions about the direction of the oxidative aromati-
zation of σH-adducts have been raised earlier in the
literature. Thus, the results of mass spectrometric study of
the processes of dihydroazine aromatization have been
compared with the experimental data on their chemical
oxidation.30 The well-known Fukuzumi research group has
studied in detail the phenomenon of the cleavage of C–H
and C–C bonds in the one-electron oxidation of 9-alkyl-
10-methyl-9,10-dihydroacridines, including the effect of
size and structure of the alkyl substituent. Using kinetic
and ESR measurements, fast cyclic voltammetry, and
theoretical calculations, it was shown that the cleavage of
C–C bond becomes dominant in the case of bulky tertiary
alkyl substituents.31 Gallardo and Guirado have carried out
the thermodynamic studies for a series of the nitroaromatic
σH-adducts containing heteroatom nucleophile residues
(OH, OR, SR, F).32 They have shown that under electro-
chemical oxidation conditions one-electron oxidation occurs
followed by homolytic elimination of the nucleophilic
group and the subsequent recovery of the initial substrate.
The authors have also showed that the dissociation energies
of bonds at the geminal carbon atom are the determining
factors in the direction of aromatization.
The analysis of the literature on the C–H functionali-
zation, not catalyzed by transition metals, of both aromatic
and heteroaromatic π-deficient compounds reveals a
interesting feature: about 70% of studies are devoted to the
Figure 1. Investigated range of σH-adducts 1–34.
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Chemistry of Heterocyclic Compounds 2019, 55(9), 956–963
Table 1. Selected crystal characteristics of dihydroacridines
The studied dihydroacridines 1–34 were subjected to
from X-ray diffraction data analysis
preparative electrochemical oxidation. Two paths of
Dihydroacridine
φ*, deg
ΣN**, deg
aromatization were observed: either the formation of the
H
SN product or the destructive oxidation to the initial
35.24
23.42
355.2(3)
358.0(3)
1
4
acridinium cation. The direction of the process depends on
the nature of the nucleophile: in the case of C-nucleophiles
(compounds 1–17) the yield of the target SNH products was
close to quantitative.35 With regards to anodic aromatiza-
tion of the σH-adducts with heteroatomic nucleophiles 18–34,
only the initial acridinium salt was isolated in quantitive
yield (Scheme 2). At the same time, under analogous
conditions of electrochemical oxidation the amination of
acridinium with primary amines was realized with good
yields (40–85%) of 9-aminoacridines 36a–с (Scheme 3).
Intermediates 35a–c could not be isolated.37
33.99
34.03
34.84
27.60
21.95
30.18
21.74
28.36
6.66
29.67
24.14
32.44
34.97
27.91
355.8(3)
355.8(3)
355.6(1)
358.8(1)
358.4
357.6
358.8(3)
358.1(3)
359.94(47)
357.4(3)
10
11
18
19
20
21
23
24
27
358.3(9)
355.5(9)
356.1(9)
357.6(7)
Scheme 2
31
* Deviation from planarity in the acridine moiety (180° minus dihedral
angle between phenylene fragments).
** Sum of the valence angles at the endocyclic nitrogen atom of the
acridine moiety.
crystal packing can reach ten degrees (compound 18). This
peculiarity does not allow us to establish correlation
between the experimental angles and the calculated
quantum-mechanical characteristics.
The sum of the valence angles of the endocyclic
nitrogen atom (N–CH3 group) correlates well with the
value of the dihedral angle. Its reduction with increasing
angle is easily explained by a decrease in the conjugation
effect between the phenylene moieties and by a change of
the planar configuration of nitrogen atom to the trigonal-
pyramidal one (from sp2 to sp3 state). Thus, the X-ray
diffraction data indicate, that all the test compounds have
similar molecular geometry. The absence of fundamental
differences between them does not allow us to explain the
observed different behavior under conditions of the
electrochemical oxidation.
Scheme 3
It is possible that the cleavage of C–H or C–X bond is
associated with the steric properties of dihydroacridines.
Such studies had not previously been carried out, therefore
we performed an analysis of the X-ray diffraction data for
compounds 1, 4, 10, 11, 18–21, 23, 24, 27, and 31. All
investigated dihydroacridines have a pseudo-boat confor-
mation of the central heteroatomic ring of the acridine
moiety (Fig. 2). The nucleophilic fragment and the electron
pair of the sp3-nitrogen atom of the dihydroazine ring are
located pseudoaxially, the proton of the sp3-carbon atom is
in the pseudoequatorial position. As can be seen from the
data presented in Table 1, the deviation from planarity φ of
the acridine ring system due to formation of a dihedral
angle between the phenylene moieties varies from 6.66°
(compound 21) to 35.24° (compound 1). In this case,
molecular packing has a very significant effect on the size
of the dihedral angle, for the same structure, the difference
in φ value for the molecules in two layers of the same
Figure 2. Molecular structure of compound 27 with atoms
represented as thermal vibration ellipsoids of 50% probability.
958

Chemistry of Heterocyclic Compounds 2019, 55(9), 956–963
Scheme 4
H
+ e–
–FE0X·/X–
+ e–
.
+
X
+ X–
N
Me
D
–DC–H
–FE0X·/X–
N
Me
AcrH+
DC–X
–FE0H+/H·
+ e–
G0( )
X
X
N
H
+ H+
N
Me
AcrHX
Me
C
FE0S
FE0
– e–
H
– e–
-adduct
N
H
N
X
X
H
.
X
+
+ H+
G0
G0
C–H
N
C–X
N
Me
Me
Et
AcrH+
B
A
As already mentioned, the difference between dissocia-
tion energies of С–Н and С–Х bonds at the geminal site
(C-9) is a determining factor in the transformation of the
σH-adducts of nitroarene derivatives.32,38 We assumed that
the approach proposed for nitroarenes can be used for
heterocyclic intermediates. In order to relate the Gibbs
standard chemical reaction energy (ΔG0), the Gibbs
standard electrochemical energy (–FE0) for a one electron
transfer, and the bond dissociation energy (D) we have
used a thermodynamic cycle (Scheme 4) described
earlier.32,38–40
ΔG0C–X = –ΔG0(σ) + FE0
– FE0
(2)
(3)
X˙/X–
σH-adduct
The combination of the latter gives equation (3).
ΔG0C–H – ΔG0C–X = DC–H – DC–X – FE0SN + FE
0
H
H+/H˙
H
For a favorable implementation of the SN process, the
condition (4) must be met, which gives inequality (5).
ΔG0C–H < ΔG0
(4)
(5)
C–X
ΔG0C–H – ΔG0 < 0
C–X
The radical and radical cation intermediates shown in
Scheme 4 have been observed experimentally.41,42 The
thermodynamic cycle begins with the formation of a bond
between the 1-methylacridinium cation (AcrH+) and a
nucleophile (ΔG0(σ)) to afford the σH-adduct AcrHX. The
next step involves one-electron oxidation of the inter-
mediate (–FE0σH-adduct) and formation of the key radical
cation А. It can undergo dissociation of either the
С–Н (ΔG0C–H) or the С–X bond (ΔG0C–X), which leads to the
The difference between ΔG0
and ΔG0
depends
C–H
C–X
only on the bond dissociation energies and the standard
reaction potentials E0SN and E0H+/H, which allows to avoid
H
the difficult experimental measurement of ΔG0(σ), E0X˙/X–, and
0
E0
values. The literature values of potentials E SN
H
σH-adduct
and E0
+
are –0.46 and –1.53 V, respectively.38,43,44
TransfoHrm/Hi˙ng expressions (3) and (5) gives inequality (6),
and by substituting known values, we get the conditions
necessary for the SNH process (7).
Н
radical of SN product B or to the initial acridinium cation
0
C–H – DC–X < FE0SN + FE
(6)
(7)
H
D
D
H+/H˙
AcrH+, respectively. Radical B, generated by a proton
C–H – DC–X < 24.67 kcal/mol
H
0
H
elimination, is oxidized to the SN product C (–FE SN ). The
latter is transformed through the homolytic cleavage of the
C–X bond (DC–X into the radical cation D, which may
recombine with a hydrogen atom. To close the thermo-
dynamic cycle, protons are reduced to hydrogen (–FE0H+/H˙),
and a nucleophilic radical X˙ is transformed into anion X–
(–FE0X˙/X–). In the case of the C–X bond dissociation,
reduction of X˙ into X– is also necessary to close the cycle.
In accordance with the thermodynamic cycle, the values
of ΔG0C–H and ΔG0C–X are related by equations (1) and (2).
It should be noted that the value of DC–H for 10-methyl-
9,10-dihydroacridine has been determined and reported to
be 8045 or 72 kcal/mol.44 Since there are no values of the
dissociation energies of C(9)–X bonds of 10-methyl-9,10-
dihydroacridine in the literature, we decided to carry out
quantum-chemical calculations of these values for some
model compounds. Table 3 shows the calculated values of
bond dissociation energies for various substituents.
According to the data of thermodynamic calculations
and bond dissociation energy (BDE) calculations, the
σH-adduct obtained from C-nucleophile 1 undergoes
ΔG0C–H = –ΔG0σ + DC–H – DC–X + FE0
–
X˙/X–
0
– FE0σH-adduct – FE0SN + FE
(1)
H
H
H+/H˙
oxidation by the SN mechanism, i.e., by the cleavage of
959

Chemistry of Heterocyclic Compounds 2019, 55(9), 956–963
Table 3. C(9)–X bond dissociation energies of selected
Table 4. Enthalpies ΔH1 and ΔH2 of formal oxidation reactions
(1) and (2), respectively, of 9-substituted 10-methyl-
9,10-dihydroacridines calculated by semiempirical method PM3
10-methyl-9,10-dihydroacridines, calculated
by DFT/B3LYP 6-31G(d) and DFT 6-31G(d,p) methods46
DC–H
,
DC–X
,
D
C–H – DC–X,
Com-
pound
ΔH1,
ΔH2,
ΔH1–ΔH2,
Dihydroacridine
X
kcal/mol
66.81
71.22
71.68
64.17
67.41
66.77
66.03
kcal/mol
63.66
37.30
48.43
51.31
45.43
35.65
32.30
kcal/mol
kcal/mol
kcal/mol
kcal/mol
3.15
1
H
С
–199.20
–205.52
–206.26
–206.55
–207.54
–208.82
–203.11
–202.62
–206.68
–200.80
–200.27
–197.49
–203.82
–202.18
–204.90
–207.71
–206.93
–203.65
–196.55
–191.02
–198.04
–202.64
–198.01
–202.56
–201.23
–205.81
–200.42
–200.13
–198.23
–198.63
–202.10
–217.62
–210.83
–212.29
–199.20
–193.74
–193.74
–193.71
–193.72
–193.70
–193.66
–193.67
–193.88
–193.48
–193.43
–193.19
–195.88
–194.08
–195.25
–193.71
–193.77
–195.64
–198.26
–196.85
–199.38
–200.52
–200.10
–197.95
–198.61
–199.76
–200.09
–198.01
–214.86
–215.03
–204.61
–197.04
–195.70
–195.67
0.00
–11.78
–12.52
–12.84
–13.82
–15.12
–9.45
–8.95
–12.80
–7.32
–6.84
–4.30
–7.94
–8.10
–9.65
–14.00
–13.16
–8.01
+1.71
+5.83
+1.34
–2.12
+2.09
–4.61
–2.62
–6.05
–0.33
–2.12
+16.63
+16.40
+2.51
–20.58
–15.13
–16.62
33.92
23.25
12.86
21.98
31.12
33.73
27
1
2
3
4
5
6
7
8
9
31
С
С
35a
35c
37
С
С
С
38
С
С
С
С
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
27
28
30
31
33
35a
35b
35c
С
С
С
С
С
С
the C–H bond and the retention of the C-substituent (Ph) in
the structure. Adducts 35a,c, obtained by the interaction of
AcrH+ with primary amines, behave similarly. For the
intermediates with secondary amines 37, 38 and sulfur
derivative 27, DC–H – DC–X > 24.67 kcal/mol, so the oxidative
process passes destructively with cleavage of the C–X
bond. According to the calculations, the P-centered compound
31 is in the boundary region, and this makes cleavage of
the C–H bond unlikely or highly ineffective, as we have
observed experimentally. Thus, the previously proposed
prognostic approach32,39 can be extended to the field of
heterocyclic chemistry, which makes it possible to estimate
in advance the direction of the aromatization reaction.
However, the process of constructing a complete thermo-
dynamic cycle involving all the intermediates, the search
for or the calculation of all the necessary parameters for
predicting the aromatization pathway of the σH-adducts is
rather labor-intensive, and, in some cases, is completely
incapable of implementation. So, we have attempted to find
a more accessible and simple method to evaluate the
possibility of the direct C–H functionalization. We calculated
the enthalpy for formal oxidation reactions (1) and (2)
(Scheme 5) for a number of compounds by the PM3 method,
the parameterization of which is based on thermochemical
data. The results of the calculations are shown in Table 4.
С
N
N
N
N
N
N
N
N
S
S
P
P
O
NH
NH
NH
The results of the present calculations, involving a
complete optimization of the molecule geometries, indicate
a correlation between the nature of the nucleophilic
substituent and the type of oxidation reaction of the adduct.
In the case of σH-adducts with a substituent derived from a
C-nucleophile or from a primary amines, the oxidation is
accompanied by the cleavage of C–H bond and the
retention of the substituent, as evidenced by the negative
value of ΔH1–ΔH2. Anodic aromatization of the σH-adducts
derived from heteroatom nucleophiles (secondary amines,
N-heterocycles, thiols, alcohols, phosphites) proceeds
destructively with the cleavage of C–heteroatom bond and
the recovery of the initial substrate, as evidenced by the
mainly positive value of ΔH1–ΔH2.
Scheme 5
Thus, it was demonstrated that in the electrochemical
oxidative aromatization of σH-adducts, the nature of the
nucleophile is the determining factor for the reaction
pathway. The thermodynamic approach proposed earlier
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Chemistry of Heterocyclic Compounds 2019, 55(9), 956–963
for nitroarenes was successfully extended to the field of
(1H, s, 9-CH); 3.27 (3H, s, NCH3). 13C NMR spectrum:
δ, ppm: 141.9; 134.8; 132.9; 128.5; 128.2; 128.1; 128.0;
121.8; 120.4; 112.5; 51.7; 32.9. Found, %: C 78.99; H 5.66;
N 4.83. C20H17NS. Calculated, %: C 79.17; H 5.65; N 4.62.
9-(Benzylsulfanyl)-10-methyl-9,10-dihydroacridine (28).
Yield 166 mg (84%). Colorless crystals. Mp 133°C.
1H NMR spectrum, δ, ppm (J, Hz): 7.32–7.26 (4H, m,
H Ar); 7.25–7.20 (5H, m, H Ar); 7.09 (2H, d, J = 8.1, H Ar);
6.99–6.96 (2H, m, H Ar); 5.35 (1H, s, 9-CH); 3.57 (2Н, s,
CH2); 3.41 (3H, s, NCH3). 13C NMR spectrum, δ, ppm:
142.0; 137.9; 128.7; 128.4; 128.1; 128.0; 126.7; 122.3;
120.3; 112.7; 46.4; 34.8; 32.9. Found, %: C 79.45; H 6.12;
N 4.57. C21H19NS. Calculated, %: C 79.45; H 6.03; N 4.41.
9-(Isopropylsulfanyl)-10-methyl-9,10-dihydroacridine
(29). Yield 132 mg (79%). Colorless crystals. Mp 89°C.
1H NMR spectrum, δ, ppm (J, Hz): 7.29–7.23 (4H, m,
H Ar); 7.09–7.05 (2H, m, H Ar); 6.97–6.94 (2H, m, H Ar);
5.44 (1H, s, 9-CH); 3.40 (3Н, s, NCH3); 2.66–2.58 (1H, m,
CH(CH3)2); 1.13 (6H, d, J = 6.7, CH(CH3)2). 13C NMR
spectrum, δ, ppm: 142.0; 127.9; 127.8; 122.8; 120.2; 112.7;
44.9; 33.5; 32.9; 23.3. Found, %: C 75.68; H 7.15; N 5.31.
C17H19NS. Calculated, %: C 75.79; H 7.11; N 5.20.
heterocyclic chemistry. Thermodynamic studies can
explain the difference in the mechanism of σH-adducts
oxidation from the standpoint of BDE values. In addition,
the enthalpies of the studied reactions, obtained by the
semiempirical PM3 method, are in good agreement with
the experimental results on the intermediates oxidation.
Thus, the proposed calculation methods can be used for the
primary evaluation and prediction of the direction of
aromatization of the key SNH intermediates.
Experimental
1H and 13C NMR spectra were recorded on a Bruker
Avance 500 instrument (500 and 126 MHz, respectively) in
DMSO-d6 with TMS as internal standard. Elemental
analysis of carbon, hydrogen, and nitrogen was carried on
an Eurovector EA 3000 automatic analyzer. The determi-
nation of the mass fraction of fluorine was carried out by
spectrophotometric method on
a
SPECORD 200
instrument. Melting points were determined on Boetius
combined heating stages and were not corrected.
All starting reagents and solvents were obtained from
commercial sources and dried by standard procedures
before use. Compounds 1–26, 30–32, 36a–c were synthe-
sized according to the known procedures.35–37,47,48
Structures 37 and 38 were used as theoretical models and
have not been synthesized. The electrochemical oxidation
of the studied compounds was carried out in accordance
with previously described methods.35,49
Synthesis of 9,10-dihydroacridines 33, 34 (General
method). 10-Methylacridinium iodide (200 mg, 0.623 mmol)
was added to a solution of MeONa (0.685 mmol) in MeOH
(10 ml) or EtONa (0.685 mmol) in EtOH (10 ml) for the
synthesis of compound 33 and 34, respectively. The
reaction mixture was stirred at room temperature until a
colorless solution formed. The solvent then was evaporated,
and the residue was suspended in H2O. The product was
extracted with CH2Cl2, and the extract was dried over
Na2SO4. The solvent was evaporated, and the product was
recrystallized from MeOH (for compound 33) or EtOH (for
compound 34).
10-Methyl-9-(3-nitro-1,2,4-triazol-1-yl)-9,10-dihydro-
acridine (26). Yield 143 mg (75%). Yellow crystalline
powder. Mp 154–155°C. 1H NMR spectrum, δ, ppm
(J, Hz): 8.54 (1H, s, H triazole); 7.57 (2H, d, J = 7.4,
H Ar); 7.46 (2H, t, J = 7.5, H Ar); 7.31 (2H, d, J = 8.3,
H Ar); 7.23 (1H, s, 9-CH); 7.07 (2H, t, J = 7.3, H Ar); 3.54
(3H, s, NCH3). Found, %: C 62.41; H 4.33; N 22.85.
C16H13N5O2. Calculated, %: C 62.53; H 4.26; N 22.79.
9-(Methylamino)-10-methylacridinium tetrafluoro-
borate (36b). Yield 200 mg (65%). Yellow crystals.
9-Methoxy-10-methyl-9,10-dihydroacridine (33). Yield
108 mg (77%). Colorless crystals. Mp 81–82°C (mp 76–
1
77°C51). H NMR spectrum, δ, ppm: 7.49–7.35 (4H, m,
H Ar); 7.23–7.21 (2H, m, H Ar); 7.06–7.02 (2H, m, H Ar);
5.31 (1H, s, 9-CH); 3.48 (3Н, s, NCH3); 2.97 (3H, s,
OCH3). 13C NMR spectrum, δ, ppm: 141.4; 130.0; 128.8;
120.8; 119.7; 112.9; 75.9; 52.9; 32.8. Found, %: C 79.92;
H 6.85; N 6.27. C15H15NO. Calculated, %: C 79.97; H 6.71;
N 6.22.
1
Mp 202–204°C (decomp.). H NMR spectrum, δ, ppm:
10.46 (1H, s, NH); 8.50–8.47 (2Н, m, H Ar); 8.09–8.04
(4H, m, H Ar); 7.60–7.58 (2H, m, H Ar); 4.11 (3H, s,
NCH3); 3.64 (3H, s, NCH3). 13C NMR spectrum, δ, ppm:
159.0; 140.8; 136.4; 125.2; 123.8; 116.9; 112.5; 36.2; 35.8.
Found, %: C 57.99; Н 4.81; N 8.94; F 24.61. C15H15BF4N2.
Calculated, %: C 58.10; Н 4.88; N 9.03; F 24.51.
9-Ethoxy-10-methyl-9,10-dihydroacridine (34). Yield
1
113 mg (76%). Colorless crystals. Mp 60–61°C. H NMR
spectrum, δ, ppm (J, Hz): 7.45–7.43 (2H, m, H Ar); 7.40–
7.36 (2Н, m, H Ar); 7.21–7.19 (2H, m, H Ar); 7.04–7.00
(2H, m, H Ar); 5.40 (1H, s, 9-CH); 3.47 (3Н, s, NCH3);
3.32–3.22 (2Н, m, OCH2); 0.94 (3H, t, J = 7.0, CH2CH3).
13C NMR spectrum, δ, ppm: 141.5; 129.8; 128.7; 121.4;
119.7; 112.9; 74.5; 60.7; 32.8; 15.1. Found, %: C 80.19;
H 7.22; N 5.98. C16H17NO. Calculated, %: C 80.30; H 7.16;
N 5.85.
Synthesis of 9,10-dihydroacridines 27–29 (General
method). A solution of KOH (38 mg, 0.685 mmol) in EtOH
(3 ml) and the appropriate thiol (0.685 mmol) were added
to a suspension of 10-methylacridinium iodide (200 mg,
0.623 mmol) in EtOH (3 ml). The reaction mixture was
stirred at room temperature for 40–50 min, then diluted
with H2O (15 ml). A precipitate formed which was filtered
off, washed with H2O, and recrystallized from EtOH.
10-Methyl-9-(phenylsulfanyl)-9,10-dihydroacridine (27).
Yield 164 mg (87%). Colorless crystals. Mp 141–143°C
X-ray structural investigation of compounds 1, 4, 10,
11, 18–21, 23, 24, 27, and 31. Crystals were obtained by
slow evaporation of MeCN solution. X-ray diffraction
experiments were carried out on an automated diffracto-
meter Xcalibur S with CCD detector following the standard
procedure (graphite monochromator, MoKα radiation,
1
(mp 139–141°C50). H NMR spectrum, δ, ppm (J, Hz):
7.31–7.19 (5H, m, H Ar); 7.12–7.06 (4H, m, H Ar); 7.01
(2H, d, J = 8.2, H Ar); 6.85 (2H, t, J = 7.2, H Ar); 5.82
961

Chemistry of Heterocyclic Compounds 2019, 55(9), 956–963
6. Sakai, H.; Konno, K.; Murata, H. Appl. Phys. Lett. 2009, 94,
λ 0.71069 Å, ω-scanning with step 1°). The unit cell
073304.
parameters were refined using all collected spots after the
integration process. The data were not corrected for
absorption.
7. Singh, H.; Singh, H.; Sharma, S.; Singh Bedi, P. M.
Heterocycles 2015, 91, 2043.
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Serebryakova, O. G.; Rudakova, E. V.; Ustyugov, A. A.;
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Structures 1, 4, 10, 11, 18–21, 23, 24, 27, and 31 were
solved by direct methods with the SHELX97 program
package.52 Structure 11 was solved using Olex2 with the
Superflip structure solution program by charge flipping.53
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)-9 atoms in the dihydroazine rings were solved
and refined independently in isotropic approximation. All
other H atoms were calculated with AFIX and were
included in the refinement at "riding" model with a
common isotropic temperature factor. Crystallographic data
of the investigated compounds have been deposited at the
Cambridge Crystallographic Data Center (deposits CCDC
1479454 for compound 1, CCDC 1479456 for compound
4, CCDC 1479453 for compound 10, CCDC 1896716 for
compound 11, CCDC 165508 for compound 18, CCDC
929423 for compound 19, CCDC 929424 for compound
20, CCDC 929426 for compound 21, CCDC 929427 for
compound 23, CCDC 929428 for compound 24, CCDC
1896715 for compound 27, CCDC 1896717 for compound
31).
Thermodynamic and BDE calculations. All the calcu-
lations were carried out using the Gaussian 09 software.54
Optimization of the structures (opt) was carried out until
the first local energy minimum by a consecutive use of
HF/3-21, HF/6-31G(d), DFT-B3LYP/6-31G(d) bases (for
compounds containing sulfur and phosphorus, the last used
basis was DFT-B3LYP/6-31G(d,p)). A check for the global
minimum was not conducted. The calculation of the
thermodynamic parameters (freq) was carried out either on
DFT-B3LYP/6-31G(d) basis or on DFT-B3LYP/6-31G(d,p)
one (for S- and P-containing compounds). The bases used
for BDE calculations are assigned to the average accuracy
calculations.
15. Sondhi, S. M.; Singh, N.; Lahoti, A. M.; Bajaj, K.; Kumar, A.;
Lozach, O.; Meijer, L. Bioorg. Med. Chem. 2005, 13, 4291.
16. Zhu, X.-Q.; Deng, F.-H.; Yang, J.-D.; Li, X.-T.; Chen, Q.;
Lei, N.-P.; Meng, F.-K.; Zhao, X.-P.; Han, S.-H.; Hao, E.-J.;
Mu, Y.-Y. Org. Biomol. Chem. 2013, 11, 6071.
17. Kil, H. J.; Lee, I.-S. H. J. Phys. Chem. A 2009, 113, 10704.
18. Hernán-Gómez, A.; Herd, E.; Uzelac, M.; Cadenbach, T.;
Kennedy, A. R.; Borilovic, I.; Aromí, G.; Hevia, E.
Organometallics 2015, 34, 2614.
19. Hyodo, I.; Tobisu, M.; Chatani, N. Chem. Commun. 2012, 48,
308.
20. Lian, Y.; Hummel, J. R.; Bergman, R. G.; Ellman, J. A.
J. Am. Chem. Soc. 2013, 135, 12548.
21. Huang, Z.; Yang, Y.; Xiao, Q.; Zhang, Y.; Wang, J. Eur.
J. Org. Chem. 2012, 33, 6586.
22. Rogness, D. C.; Larock, R. C. J. Org. Chem. 2010, 75, 2289.
23. Tsvelikhovsky, D.; Buchwald, S. L. J. Am. Chem. Soc. 2010,
132, 14048.
24. Singh, N. P.; Kumar, R.; Prasad, D. N.; Sharma, S.; Silakari, O.
Int. J. Biol. Chem. 2011, 5, 193.
25. Metal Free C-H Functionalisation of Aromatics. Nucleophilic
Displacement of Hydrogen; Charushin, V. N.; Chupakhin, O. N.,
Eds.; Springer: Cham, 2014.
The research was financially supported by the Russian
Foundation for Basic Research (research project
No. 18-33-00124).
Analytical studies were carried out using equipment of
the Center for Joint Use ''Spectroscopy and Analysis of
Organic Compounds'' at the Postovsky Institute of Organic
Synthesis of the Russian Academy of Sciences (Ural Branch).
26. Terrier, F. Modern Nucleophilic Aromatic Substitution;
Wiley-VCH: Weinheim, 2013.
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Charushin, V. N.; Rempel, A. A. Green Chem. 2015, 17,
4401.
29. Chupakhin, O. N.; Charushin, V. N. Tetrahedron Lett. 2016,
57, 2665.
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