Oxidative SNH amidation of acridine and tautomerism of N-(acridin-9-yl)benzamides

Article abstract of DOI:10.1007/s10593-016-1841-7

[Figure not available: see fulltext.] Direct oxidative nucleophilic substitution of hydrogen atom in acridine molecule was used to synthesize 9-acylaminoacridines. The prototropic amine-imine tautomerism of these compounds was studied.

Full text of DOI:10.1007/s10593-016-1841-7

DOI 10.1007/s10593-016-1841-7
Chemistry of Heterocyclic Compounds 2016, 52(2), 104–109
Oxidative SNH amidation of acridine
and tautomerism of N‐(acridin-9-yl)benzamides
Oleg P. Demidov1, Ivan V. Borovlev1*,
Gulminat A. Amangasieva1, Elena K. Avakyan1
1
North-Caucasus Federal University,
1a Pushkina St., Stavropol 355009, Russia; е-mail: ivborovlev@rambler.ru
Translated from Khimiya Geterotsiklicheskikh Soedinenii,
2016, 52(2), 104–109
Submitted January 21, 2016
Accepted February 7, 2016
Direct oxidative nucleophilic substitution of hydrogen atom in acridine molecule was used to synthesize 9-acylaminoacridines. The
prototropic amine-imine tautomerism of these compounds was studied.
Keywords: acridine, nucleophilic substitution of hydrogen, oxidative amidation, tautomerism.
Scheme 1
The development of selective C–N bond formation
reactions is an important direction in contemporary organic
synthesis, because compounds containing amino groups or
their derivatives show various biological activity, are used
in medicinal chemistry, as well as in chemical technology
and biotechnology.1 The most general method for the
preparation of such compounds is nucleophilic substitution
of halogens or other nucleofugic groups either in the
absence of catalyst2 or under catalytic conditions.3 Direct
methods for the introduction of amine and amide
functionality in electron-rich heterocycles by activation of
C–H bonds with transition metal complexes have been
actively developed in recent years.4
In the case of electron-deficient substrates, such as
azines and nitroarenes, an attractive alternative to the
aforementioned methods is nucleophilic aromatic
substitution of hydrogen atom (SNH),5 including the
oxidative6 and vicarious7 versions of this reaction. The
methodology of oxidative nucleophilic substitution of
hydrogen atom does not require preliminary introduction of
classical leaving groups in the molecule of aromatic
substrate or reagent and the use of costly catalysts and
ligands.
oxidant can be either inorganic (air oxygen, halogens,
sulfur, metal cations etc.) or organic reagents (quinones,
carbocations, nitro compounds, etc.). In the absence of
external oxidant, the starting π-electron-deficient substrate
may also act as an oxidant.
Compared to the well known achievements in the field
of oxidative amination and alkylamination6 of azines, the
SNH amidation reaction remains little studied. The first
example of this reaction was reported in early 1990s, using
nitrobenzene.9 Subsequently, benzamidation of 1,3-dinitro-
benzene under anaerobic conditions was used to synthesize
N-(2,4-dinitrophenyl)benzamide in 12% yield.10
Our research group recently performed the first SNH
amidation of a heteroaromatic compound, namely, 1,3,7-tri-
azapyrene.11 The reaction between the heterocycle and
N-anion of the respective amide proceeded in anhydrous
DMSO at room temperature, with air oxygen acting as the
oxidant.
The aim of this work was to study the possibilities for
introducing N-amide functionality in the ring of acridine
(1) by direct substitution of hydrogen atom under the
aforementioned conditions. Regioselective SNH reactions at
position 9 of acridine system are well known,12 but in the
case of N-nucleophiles always occur with difficulty and
The mechanism of SNH reaction includes the formation
of σH-adduct, followed by its aromatization (Scheme 1).
The second step is always rate limiting for the whole
process, because the formally eliminated hydride anion is a
very poor nucleofuge. The elimination step occurs as a
redox process that includes a sequence of electron transfer,
proton transfer, and another electron transfer from
σH-adduct to the oxidant (EPE mechanism).8 The external
0009-3122/16/52(2)-0104©2016 Springer Science+Business Media New York
104

Chemistry of Heterocyclic Compounds 2016, 52(2), 104–109
produce unreliable results. For example, acridine
During our earlier studies of such SNH reactions of 1,3,7-tri-
azapyrene as hydroxylation,19a alkoxylation,19b,c ami-
nation,19a and alkylamination,19d we successfully used the
common one-electron oxidant K3Fe(CN)6. Applying it to
the benzamidation of acridine shortened the reaction
duration to 8 h and increased the product yield to 78%
(Table 1, experiment 3). The same system of reagents was
successfully used at room temperature to interact acridine
with other primary aromatic amides both with electron-
donating and electron-withdrawing substituents in the
benzene ring (Table 1, experiments 4–7).
underwent Chichibabin reaction with sodium amide only at
180°C in N,N-dimethylaniline13a or upon fusion with
NaNH2.13b However, the yield of 9-aminoacridine in both
cases was only 31%; also significant amounts of the
starting material and 9,9'-biacridane were isolated.
We should note that derivatives of acridine, and
especially those of 9-aminoacridine, have a wide range of
applications as fluorescent biochemical markers,14 as well
as antitumor,15 antibacterial,16 antiHIV,17 and antimalarial
drugs.18
Before optimizing the reaction conditions for the
introduction of N-amide group, we first studied the
benzamidation of acridine (1). At first, the benzamide
anion was obtained by treatment with sodium hydride in
anhydrous DMSO, under the conditions that are known to
enhance the nucleophilicity of anions due to the absence of
solvate shell. It was found that the interaction of acridine
(1) with a 6-fold molar excess of benzamide N-anion in
DMSO occurred quite slowly at room temperature. Thus,
48% of 9-benzoylaminoacridine (2) along with 50% of the
starting acridine were isolated from the reaction mixture
after 54 h (Scheme 2, Table 1, experiment 1). Remarkably,
increasing the temperature to 65–70°C practically did not
accelerate the benzamidation reaction, but led to the
appearance of by-products and decreased the yield of
product 2 (Table 1, experiment 2).
Contrary to the case of 1,3,7-triazapyrene,11 the reaction
of acridine with amides of aliphatic carboxylic acids
(formic, acetic, propionic, and isobutyric acids) proceeded
smoothly under the conditions described above, forming
high yields of the respective 9-acylaminoacridines
(Table 1, experiments 8–11).
It should be noted that, while 1H NMR spectra (DMSO-d6)
of compounds 7–10 obtained from aliphatic amides fully
corresponded to the structure of 9-acylaminoacridine, the
spectra of their aromatic analogs 2–6 featured significantly
broadened proton signals, preventing accurate assignment
of these signals (Fig. 1a). Apparently, the averaging of
spectra was caused by the non-degenerate prototropic
aminoacridine-acridanimine tautomerism known in
compounds of acridine series.20 In our case, this
tautomerism occurred between the acylamine form A and
acylimine form B of compounds 2–6 (Scheme 3).
The rates of tautomeric transformations in DMSO
solution were quite different for compounds 2–6. For
example, besides the proton multiplets of one tautomer, the
spectrum of 9-benzoylaminoacridine (2) also contained a
set of significantly broadened singlets from the other
tautomer at ~7.2, 7.5, 8.0, and 11.8 ppm. The ratio of
tautomers was ~ 9:1 according to the integrated intensity of
signals. Therefore, in the case of amide 2, the prototropic
transformations became slow on NMR timescale, and
distinct signals of both tautomers were simultaneously
observed, uncharacteristically for such a polar solvent.21a
We assumed that a possible reason for the slow reaction
progress at room temperature was the low efficiency of air
oxygen as oxidant during the aromatization of σH-adduct.
Scheme 2
Table 1. The synthesis conditions and yields 9-acylaminoacridines 2–10
Experi-
ment
R
Reaction product
Temperature, °С
Oxidant
Reaction time, h
Yield, %
1
Ph
Ph
Room
65–70
Room
Room
Room
Room
Room
Room
Room
Room
Room
O2 (air)
54
54
8
48*
24**
78
2
2
2
O2 (air)
3
Ph
K3Fe(CN)6
K3Fe(CN)6
K3Fe(CN)6
K3Fe(CN)6
K3Fe(CN)6
K3Fe(CN)6
K3Fe(CN)6
K3Fe(CN)6
K3Fe(CN)6
2
4
4-MeC6H4
4-MeOC6H4
4-O2NC6H4
2-O2NC6H4
H
8
92
3
5
8
96
4
6
12
12
10
10
8
78
5
7
75
6
8
71
7
9
Me
73
8
10
Et
67
9
11
2-Pr
8
66
10
* Isolated 50% of the starting compounds.
** Isolated 20% of the starting compounds.
105

Chemistry of Heterocyclic Compounds 2016, 52(2), 104–109
Scheme 3
Scheme 4
The addition a small amount of trifluoroacetic acid to the
solution of amide 2 in DMSO-d6 resulted, as expected, in a
simpler spectrum, since both tautomers were protonated to
the same cation, in which the positive charge was
delocalized between two nitrogen atoms (Scheme 3 and
Fig. 1b). However, the signals of second tautomer were not
identified in the spectra of amides 3–6, indicating a higher
rate of tautomeric transformations. Taking this into account,
1H and 13C NMR spectra are further reported for the
protonated forms of compounds 2–6 (Experimental).
In order to determine the major tautomer in the
equilibrium mixture of 9-benzoylaminoacridine (2), it was
necessary to obtain model compounds of tautomers A and
B, which usually has been achieved in the form of their
fixed (N-methylated) derivatives.21b Methylation of the
ambident anion 11 of compound 2 with methyl iodide at
room temperature in anhydrous acetonitrile (Scheme 4)
gave a mixture of compounds. An fixed analog of tautomer
A, N-(acridin-9-yl)-N-methylbenzamide (12) was isolated
from this mixture, resulting from methylation at the
exocyclic nitrogen atom.
The analog of tautomer B was N-(10-methyl-10H-
acridin-9-ylidene)benzamide (14), which could be isolated
in merely 6% yield from attempted oxidative benz-
amidation of N-methylacridinium methyl sulfate (13)
(Scheme 5). The main product from this reaction was
N-methylacridone 15.
The acridone 15 was likely formed during the hydrolysis
of oxidative benzamidation product 14. Such hydrolysis
may occur not only at the isolation step, but also in the
reaction mixture due to the presence of water formed
during oxidation of the σ-adduct.
The structures of model compounds 12 and 14 were
proved conclusively by homonuclear and heteronuclear 2D
NMR experiments. A key spectral feature for establishing
the methyl group position in compound 12 was the
1
coupling of methyl group protons in Н–13С HSQC and
HMBC spectra with the carbon atom of carbonyl group
(170.8 ppm) and C-9 atom (145.5 ppm) of the acridine
fragment. In the case of compound 14, the protons of NCH3
group were coupled to the C-4a(10a) atom (141.4 ppm)
and C-4(5) atom (116.2 ppm). In this study we assigned all
1H and 13C NMR signals of compounds 12 and 14 and also
identified the missing C-9 signal in one-dimensional 13C
NMR spectrum of compound 4 (150.7 ppm) (see the
Experimental and the Supplementary information file).
The comparison of 1H NMR spectrum of
9-benzoylaminoacridine (2) (Fig. 1a) with the spectra of
model compounds 12 and 14 (Fig. 1c and 1d, respectively)
indicated that the benzoylamine form A was the major
component at equilibrium (the content of benzoylimine
form В did not exceed 10%). Certainly, the absence of
signal broadening in NMR spectra of compounds 7–10 did
not rule out the presence of an equilibrium: the equilibrium
was merely strongly shifted towards the acylamine
tautomer.
Thus, acridine readily underwent direct oxidative
substitution of hydrogen atom with an N-amide group. The
amidation with separately prepared N-anion of aliphatic or
aromatic amide in anhydrous DMSO occurred at room
temperature in the presence of K3Fe(CN)6, enabling the
synthesis of 9-acylaminoacridines in a single step and in
high yields. The obtained amides showed prototropic
tautomerism.
Scheme 5
106

Chemistry of Heterocyclic Compounds 2016, 52(2), 104–109
1
Figure 1. H NMR spectra: a) 9-benzoylaminoacridine (2) in DMSO-d6, b) 9-benzoylaminoacridine (2) in DMSO-d6 + CF3COOH,
c) N-(acridin-9-yl)-N-methylbenzamide (12) in DMSO-d6, d) N-(10-methyl-10H-acridin-9-ylidene)benzamide (14) in DMSO-d6.
Experimental
1H and 13C NMR spectra were acquired on a Bruker
Avance HD 400 instrument (400 and 100 MHz,
respectively); the solvent signals of DMSO-d6 were used as
4-nitrobenzamide). The products were further purified by
recrystallization from the appropriate solvents.
N-(Acridin-9-yl)benzamide (2). Yield 116 mg (78%),
yellow crystals, mp 235–236°С (EtOAc) (mp 166–169°С24).
1H NMR spectrum (DMSO-d6 + CF3COOH)*, δ, ppm
(J, Hz): 7.66 (2H, dd, J = 7.3, J = 7.6, H-3',5' Ph); 7.75
(1H, t, J = 7.3, H-4' Ph); 7.88 (2H, dd, J = 7.6, J = 8.7,
H-2,7); 8.24 (2H, d, J = 7.6, H-2',6' Ph); 8.28 (2H, dd,
J = 7.6, J = 8.6, H-3,6); 8.38 (2H, d, J = 8.6, H-4,5); 8.48
(2H, d, J = 8.7, H-1,8). 13C NMR spectrum (DMSO-d6),
δ, ppm: 123.1; 124.4; 126.2; 128.1; 128.7; 129.3; 130.5;
132.2; 133.6; 140.6; 149.0; 166.6. Found, m/z: 299.1184
[М+H]+. C20H15N2O. Calculated, m/z: 299.1179.
1
internal standard22 (2.50 ppm for H nuclei, 40.45 ppm for
13С nuclei). 1Н–13С HSQC and HMBC spectra were
acquired on the same instrument. Mass spectral analysis
was performed on a Bruker UHR-TOF maXis Impact
instrument (electrospray ionization). Melting points were
determined with a PTP-1 apparatus. The reaction progress
and purity of the obtained compounds were controlled by
TLC on Silufol UV-254 plates.
Sodium hydride (60% suspension in paraffin oil) was
purchased from Merck. 10-Methylacridinium methyl
sulfate (13) was obtained according to a published
procedure.23 The commercially available reagents were
used without additional purification.
Synthesis of N-(acridin-9-yl)acylamides 2–10 (General
method). The reaction was performed in a vessel protected
from air moisture. Sodium hydride (60% suspension in oil,
120 mg, 3 mmol) was added with stirring to a solution of
the appropriate amide (3 mmol) in anhydrous DMSO
(4 ml). After the evolution of hydrogen ceased (~0.5 h), the
reaction mixture was treated with acridine (1) (89.5 mg,
0.5 mmol), K3Fe(CN)6 (1 g, 3 mmol) and vigorously stirred
at room temperature for the duration indicated in Table 1.
Then the mixture was poured into cold water (50 ml) and
acidified with dilute HCl solution to pH ~7. The precipitate
was filtered off, washed with water, dried (when isolating
the amide 5, the precipitate on filter was washed at first
with 100 ml of hot water (~90°C) to remove the exess of
N-(Acridin-9-yl)-4-methylbenzamide (3). Yield 144 mg
(92%), yellow crystals, mp 255–256°С (EtOH–EtOAc).
1H NMR spectrum (DMSO-d6 + CF3COOH), δ, ppm (J, Hz):
2.46 (3H, s, CH3); 7.47 (2H, d, J = 8.1, H-3',5' Ar); 7.82 (2H,
br. t, J = 8.0, H-2,7); 8.13 (2H, d, J = 8.1, H-2',6'); 8.19 (2H,
br. t, J = 8.0, H-3,6); 8.31 (2H, d, J = 8.7, H-4,5); 8.37 (2H, d,
J = 8.7, H-1,8). 13C NMR spectrum (DMSO-d6 + CF3COOH),
δ, ppm: 21.2; 121.4; 122.1; 126.3; 127.3; 128.7; 129.3;
130.0; 136.4; 141.5; 143.3; 151.1; 167.2. Found, m/z: 313.1353
[М+H]+. C21H17N2O. Calculated, m/z: 313.1335.
N-(Acridin-9-yl)-4-methoxybenzamide (4). Yield 157 mg
(96%), yellow crystals, mp 263–264°С (EtOH–EtOAc).
1H NMR spectrum (DMSO-d6 + CF3COOH), δ, ppm (J, Hz):
3.91 (3H, s, CH3O); 7.19 (2H, d, J = 8.8, H-3',5' Ar); 7.83
* Here and further the 1H and 13C NMR signals of trifluoroacetic acid are not
listed. The atom numbering in phenyl group is indicated with apostrophes.
107

Chemistry of Heterocyclic Compounds 2016, 52(2), 104–109
(2H, br. t, J = 7.5, H-2,7); 8.18–8.25 (4H, m, H-3,6,2',6'
d, J = 6.9, CH(CH3)2); 3.02 (1H, m, CH(CH3)2); 7.64 (2H,
br. t, J = 7.5, H-2,7); 7.86 (2H, br. t, J = 8.2, H-3,6); 8.07
(2H, d, J = 8.6, H-4,5); 8.17 (2H, d, J = 8.7, H-1,8); 10.59
(1H, s, NH). 13C NMR spectrum (DMSO-d6), δ, ppm: 19.7;
34.6; 122.7; 124.3; 125.9; 129.3; 130.4; 140.3; 148.9;
176.4. Found, m/z: 265.1342 [М+H]+. C17H17N2O.
Calculated, m/z: 265.1335.
Ar); 8.31 (2H, d, J = 8.7, H-4,5); 8.39 (2H, d, J = 8.7,
H-1,8). 13C NMR spectrum (DMSO-d6 + CF3COOH), δ, ppm:
55.7 (CH3); 114.0 (C-3',5' Ar); 122.0 (C-8a,9a); 122.2
(C-4,5); 125.0 (C-1' Ar); 126.1 (C-1,8); 126.9 (C-2,7);
130.7 (C-2',6' Ar); 135.5 (C-3,6); 142.3 (C-4a,10a); 150.7
(C-9); 163.0 (C-4' Ar); 166.8 (C=O). Found, m/z: 329.1292
[М+H]+. C21H17N2O2. Calculated, m/z: 329.1285.
N-(Acridin-9-yl)-N-methylbenzamide
(12).
The
N-(Acridin-9-yl)-4-nitrobenzamide (5). Yield 134 mg
reaction was performed in a vessel protected from air
moisture. Sodium hydride (60% suspension in oil, 40 mg,
1 mmol) was added with stirring to a solution of 9-benzoyl-
aminoacridine (2) (149 mg, 0.5 mmol) in anhydrous
acetonitrile (4 ml). After the evolution of hydrogen ceased
(~0.5 h), the reaction mixture was treated with methyl
iodide (142 mg, 1 mmol) and vigorously stirred for 2 h.
Then the mixture was poured on ice (~50 g) and acidified
with dilute HCl solution to pH ~7. The precipitate was
filtered off, washed with water, dried, and crystallized from
ethyl acetate. Yield 19 mg (12%), beige crystals, mp 209–
1
(78%), orange crystals, mp 298–299°С (EtOH). H NMR
spectrum (DMSO-d6 + CF3COOH), δ, ppm (J, Hz): 7.80 (2H,
br. t, J = 8.1, H-2,7); 8.17 (2H, br. t, J = 8.0, H-3,6); 8.30
(2H, d, J = 8.6, H-4,5); 8.40 (2H, d, J = 9.0, H-2',6'); 8.44
(2H, d, J = 9.1, H-1,8); 8.49 (2H, d, J = 9.0, H-3',5' Ar).
13C NMR spectrum (DMSO-d6 + CF3COOH), δ, ppm: 121.9;
122.6; 123.8; 126.0; 127.0; 130.1; 135.3; 138.9; 142.7 (2C);
149.9; 166.1. Found, m/z: 344.1043 [М+H]+. C20H14N3O3.
Calculated, m/z: 344.1030.
N-(Acridin-9-yl)-2-nitrobenzamide (6). Yield 129 mg
1
1
(75%), yellow crystals, mp 265–266°С (EtOH). H NMR
210°С (EtOAc). H NMR spectrum (DMSO-d6), δ, ppm
spectrum (DMSO-d6 + CF3COOH), δ, ppm (J, Hz): 7.88–
7.95 (3H, m, H-2,7, H-4' Ar); 8.05 (1H, br. t, J = 7.6,
H-5' Ar); 8.21–8.28 (3H, m, H-3,6, H-6' Ar); 8.32 (1H, d,
J = 8.1, H-3' Ar); 8.35 (2H, d, J = 8.7, H-4,5); 8.57 (2H,
(J, Hz): 3.57 (3H, s, CH3); 6.88 (2H, br. t, J = 7.6, H-3',5'
Ph); 7.00 (1H, br. t, J = 7.4, H-4' Ph); 7.11 (2H, d, J = 7.3,
H-2',6' Ph); 7.74 (2H, br. t, J = 8.0, H-2,7); 7.86 (2H, br. t,
J = 8.0, H-3,6); 8.13 (2H, d, J = 8.7, H-4,5); 8.18 (2H, d,
J = 8.6, H-1,8). 13C NMR spectrum (DMSO-d6), δ, ppm:
37.9 (CH3); 122.8 (C-8a,9a); 123.2 (C-1,8); 126.5 (C-2',6'
Ph); 127.5 (C-3',5' Ph); 127.7 (C-2,7); 129.7 (C-4,5); 130.0
(C-4' Ph); 130.7 (C-3,6); 135.7 (C-1' Ph); 145.5 (C-9);
149.1 (C-4a,10a); 170.8 (C=O). Found, m/z: 313.1348
[М+H]+. C21H17N2O. Calculated, m/z: 313.1335.
d, J = 8.7, H-1,8). 13C NMR spectrum (DMSO-d6
+
CF3COOH), δ, ppm: 121,9; 122.5; 124.7; 125.8; 127.3;
129.9; 131.6; 131.9; 134.6; 135.7; 142.6 (2C); 146.4;
165.7. Found, m/z: 344.1042 [М+H]+. C20H14N3O3.
Calculated, m/z: 344.1030.
N-(Acridin-9-yl)formamide (7). Yield 79 mg (71%), pale-
1
yellow crystals, subl. 220°С (EtOAc). H NMR spectrum
Benzamidation of N-methylacridinium methyl sulfate
(13). The reaction was performed in a vessel protected
from air moisture. Sodium hydride (60% suspension in oil,
120 mg, 3 mmol) was added with stirring to a solution of
benzamide (363 mg, 3 mmol) in anhydrous DMSO (4 ml).
After the evolution of hydrogen ceased (~0.5 h), N-methyl-
acridinium methyl sulfate (13) (152.5 mg, 0.5 mmol) and
K3Fe(CN)6 (1 g, 3 mmol) were added, and the reaction
mixture was vigorously stirred for 3 h. The mixture was
then poured on crushed ice (~50 g), allowed to warm to
room temperature, and acidified with dilute HCl solution to
pH ~7. The precipitate was filtered off, washed with water,
and dried. The obtained mxture was separated by dry silica
gel flash chromatography,26 eluting the first fraction with
benzene and the second fraction with ethyl acetate. The
first colorless fraction after evaporation of solvent gave
83 mg (79%) of 10-methyl-10H-acridin-9-one (15).
Yellow crystals, mp 202–203°С (benzene) (mp 203°С
(benzene)27). The second, pale-yellow fraction contained
19 mg (6%) of N-(10-methyl-10H-acridin-9-ylidene)-
benzamide (14). Yellow crystals, mp 187–188°С (EtOAc).
1H NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 3.92 (3H,
s, CH3); 7.25 (2H, dd, J = 7.8, J = 8.2, H-2,7); 7.49 (2H, br.
t, J = 7.5, H-3',5' Ph); 7.58 (1H, br. t, J = 7.3, H-4' Ph);
7.76 (2H, dd, J = 7.8, J = 8.2, H-3,6); 7.81 (2H, br. d,
J = 8.2, H-4,5); 7.96 (2H, d, J = 7.8, H-2',6' Ph); 8.04 (2H,
dd, J = 8.2, J = 1.2, H-1,8). 13C NMR spectrum (DMSO-d6),
δ, ppm: 34.4 (CH3); 116.2 (C-4,5); 117.9 (C-8a,9a); 121.6
(C-2,7); 127.1 (C-1,8); 128.6 (C-2',6'); 128.7 (C-3',5');
(DMSO-d6), δ, ppm (J, Hz): 7.66 (2H, br. t, J = 7.3, H-2,7);
7.88 (2H, br. t, J = 7.5, H-3,6); 8.16 (2H, d, J = 8.5, H-4,5);
8.18 (2H, d, J = 8.6, H-1,8); 8.70 (1H, s, CHO); 10.93 (1H,
s, NH). 13C NMR spectrum (DMSO-d6), δ, ppm: 122.0;
124.4; 126.0; 129.3; 130.5; 138.9; 148.9; 161.0. Found, m/z:
223.0866 [М+H]+. C14H11N2O. Calculated, m/z: 223.0866.
N-(Acridin-9-yl)acetamide (8). Yield 86 mg (73%),
pale-yellow crystals, mp 274–275°С (EtOAc) (mp 277–
279°С (acetone)25). 1H NMR spectrum (DMSO-d6), δ, ppm
(J, Hz): 2.36 (3H, s, CH3); 7.62 (2H, br. t, J = 7.7, H-2,7);
7.86 (2H, br. t, J = 8.0, H-3,6); 8.14 (2H, d, J = 8.5, H-4,5);
8.17 (2H, d, J = 8.6, H-1,8); 10.66 (1H, s, NH). 13C NMR
spectrum (DMSO-d6), δ, ppm: 23.0; 122.5; 124.6; 125.8;
129.2; 130.4; 140.4; 148.9; 169.5. Found, m/z: 237.1028
[М+H]+. C15H13N2O. Calculated, m/z: 237.1022.
N-(Acridin-9-yl)propionamide (9). Yield 84 mg
1
(67%), yellow crystals, subl. 220°С (EtOAc). H NMR
spectrum (DMSO-d6), δ, ppm (J, Hz): 1.26 (3H, t, J = 7.5,
CH3); 2.70 (2H, q, J = 7.5, CH2); 7.63 (2H, br. t, J = 7.6,
H-2,7); 7.86 (2H, br. t, J = 8.3, H-3,6); 8.12 (2H, d, J = 8.7,
H-4,5); 8.17 (2H, d, J = 8.7, H-1,8); 8.70 (1H, s, CHO);
10.60 (1H, s, NH). 13C NMR spectrum (DMSO-d6), δ,
ppm: 9.9; 28.9; 122.6; 124.5; 125.8; 129.2; 130.4; 140.4;
148.9; 173.3. Found, m/z: 251.1186 [М+H]+. C16H15N2O.
Calculated, m/z: 251.1179.
N-(Acridin-9-yl)isobutyramide (10). Yield 87 mg
(66%), pale-yellow crystals, subl. 225°С (EtOAc).
1H NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 1.32 (6H,
108

Chemistry of Heterocyclic Compounds 2016, 52(2), 104–109
8. Matern, A. I.; Charushin, V. N.; Chupakhin, O. N. Russ.
132.3 (C-4'); 133.4 (C-3,6); 134.5 (C-1'); 141.4 (C-4a,10a);
152.7 (C-9); 176.0 (C=O). Found, m/z: 313.1349 [М+H]+.
C21H17N2O. Calculated, m/z: 313.1335.
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This work was performed with financial support from
the Ministry of Education and Science of Russian
Federation (project 4.141.2014/K).
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