8-R-5,7-Dinitroquinolines in [3+2] cycloaddition reactions with N-methylazomethine ylide

Article abstract of DOI:10.1007/s11172-013-0141-y

Novel derivatives of isoindole and dihydroisoindole fused to the pyridine ring were obtained by 1,3-dipolar cycloaddition reactions of N-methylazomethine ylide with substituted 5,7-dinitroquinolines. The substituents in the benzene ring were found to affe

Full text of DOI:10.1007/s11172-013-0141-y

Russian Chemical Bulletin, International Edition, Vol. 62, No. 4, pp. 1052—1059, April, 2013
1052
8ꢀRꢀ5,7ꢀDinitroquinolines in [3+2] cycloaddition reactions
with Nꢀmethylazomethine ylide*
M. A. Bastrakov,a A. I. Leonov,a A. M. Starosotnikov,a I. V. Fedyanin,b and S. A. Sheveleva
aN. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5328. Eꢀmail: b_max82@mail.ru
bA. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
28 ul. Vavilova, 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 6549. Eꢀmail: octy@xrlab.ineos.ac.ru
Novel derivatives of isoindole and dihydroisoindole fused to the pyridine ring were obꢀ
tained by 1,3ꢀdipolar cycloaddition reactions of Nꢀmethylazomethine ylide with substituted
5,7ꢀdinitroquinolines. The substituents in the benzene ring were found to affect the cycloaddiꢀ
tion outcome.
Key words: 1,3ꢀdipolar cycloaddition, quinolines, nitro compounds, azomethine ylides,
polycyclic systems.
Scheme 1
[3+2] Cycloaddition reactions are among key tools in
modern heterocyclic chemistry.1 The present paper is the
first one in a series of publications concerned with systemꢀ
atic investigations of 1,3ꢀdipolar cycloaddition to benzꢀ
eneꢀfused azines containing one or two nitro groups in the
benzene ring.
Recently, we have reported on the first example of
[3+2] cycloaddition reactions of Nꢀmethylazomethine
ylide (1) with nitroarenes.2,3 We have studied mainly
monoꢀ and dinitrobenzoazoles and 6,8ꢀdinitroquinoline
(2) as a representative of the azine series. NꢀMethylꢀ
azomethine ylide (1) used as a 1,3ꢀdipole was generated
in situ from paraformaldehyde and sarcosine in boiling
toluene (Scheme 1).
In all cases, the cycloaddition occurred at the aromatꢀ
ic carbon—carbon bonds activated by the nitro groups in
the starting nitroarene, yielding the pyrrolidine (e.g., comꢀ
pound 3) or pyrroline ring.
i. PhMe, 110 C.
In the next step of these investigations, we found it
interesting to study the pathways and regularities of [3+2]
cycloaddition reactions in the series of dinitrobenzenes
fused to sixꢀmembered heterocycles (e.g., pyridine). Here
we studied derivatives of 5,7ꢀdinitroquinoline, which is
a structural isomer of 6,8ꢀdinitroquinoline. Investigations
of such structures are important and meet current chalꢀ
lenges because many quinoline derivatives exhibit useful
biological activity. The quinoline fragment is part of many
alkaloids and drugs.4 In particular, nitroxalin (or 8ꢀhyꢀ
droxyꢀ5ꢀnitroquinoline) is commercially produced by
modern pharmaceutical industry. This broadꢀspectrum
therapeutic agent is efficient against some Gramꢀpositive and
Gramꢀnegative bacteria and Candida and other fungi.5
Chloride 4 (see Refs 6, 7), which can be prepared from
commercial 8ꢀhydroxyquinoline, was employed as a startꢀ
ing material for the synthesis of 8ꢀRꢀ5,7ꢀdinitroquinoꢀ
lines. The Cl atom in compound 4 is a good leaving group
that can be displaced by many nucleophiles.7—11 We used
this structural feature to obtain quinolines 5—16 (Scheme 2,
Table 1).
The compounds obtained were studied in 1,3ꢀdipolar
cycloaddition reactions with Nꢀmethylazomethine ylide.
* Dedicated to Academician of the Russian Academy of Sciences
I. P. Beletskaya on the occasion of her anniversary.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 1051—1058, April, 2013.
1066ꢀ5285/13/6204ꢀ1052 © 2013 Springer Science+Business Media, Inc.

[3+2] Cycloaddition to 8ꢀRꢀ5,7ꢀdinitroquinolines
Russ.Chem.Bull., Int.Ed., Vol. 62, No. 4, April, 2013
1053
Table 1. Reaction conditions and yields of the nucleophilic substitution products from chloride 4
NuН
Reaction conditions
Reaction
product
Yield
(%)
Solvent
T/C
t/h
PhSH
BnSH
Et3N, DME
Et3N, DME
Et3N, DME
Et3N, DME
Et3N, DME
Et3N, DME
Na2CO3, CH3CN
MeONa, MeOH
MeOH
20
20
20
20
20
20
81
65
20
20
20
20
1
1
2
1.5
1
0.5
2
1.5
1
1.5
1.5
2.5
5
6
7
8
9
10
11
12
13
14
15
16
88
86
74
58
83
63
89
99
85
86
90
85
2ꢀFurylmethanethiol
cycloꢀС6Н11—SН
4ꢀCl—C6H4—SН
НSCH2CO2Me
PhOH
MeOH
Me2NH
Piperidine
Morpholine
4ꢀCl—C6H4—NН2
EtOH
EtOH
EtOH
Scheme 2
The reactions with sulfides 9 and 10 gave not only the
expected pyrrolines 21a,b but also their oxidation prodꢀ
ucts, viz., pyrroles 22a,b (Scheme 4).
Scheme 4
We found that the cycloaddition to sulfides 5—8 occurs
only at the C(5)—C(6) bond activated by the nitro group.
Apparently, the reaction involves the formation of tricyclic
intermediates A, which promptly undergo in situ aromatiꢀ
zation with elimination of HNO2. Thus, we synthesized
new pyrroline derivatives 17—20 (Scheme 3).
Scheme 3
R = 4ꢀClC6H4 (9, 21a, 22a), CH2CO2Me (10, 21b, 22b)
i. PhMe, reflux.
The structures of all the compounds obtained as well
as the cycloaddition pathway were confirmed by NMR
spectroscopy and Xꢀray diffraction data for tricyclic prodꢀ
uct 18 (Fig. 1).
The crystal structures of such fused quinolineꢀbased
heterocycles have not yet been described. The geometrical
parameters of their structural fragments are close to the
average values in known compounds (Table 2). The cyclic
fragment of structure 18 in the crystal shows a significantꢀ
ly nonplanar conformation of the quinoline ring: the torꢀ
R = Ph (17), Bn (18), cycloꢀC6H11 (19), furfuryl (20)
i. PhMe, 110 C.

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Russ.Chem.Bull., Int.Ed., Vol. 62, No. 4, April, 2013
Bastrakov et al.
O(1)
N(3)
sion angle C(1)—C(2)—C(10)—C(6), which is a twist
distortion indicator, is 4.18(2) and the N(1) atom deꢀ
viates from the plane of the second aromatic ring
C(6)C(7)C(11)C(8)C(9)C(10) by 0.104(3) Å. The fiveꢀ
membered ring adopts an envelope conformation: the N(2)
atom is off the plane as far as 0.406(3) Å. As expected, the
geometry of the N(2) atom is pyramidal (the sum of the
angles is 335.7(5)). The nitro group makes a considerable
angle with the plane of the quinoline ring: the characterisꢀ
tic torsion angle C(7)—C(6)—N(3)—O(2) is 37.8(3).
Since the atoms of the nitro group in the crystal packing
are not involved in strong intermolecular interactions
(the O...H distance for the shortest C—H...O contact is
2.528 Å), the observed rotation of the nitro group is probꢀ
ably due to the intramolecular interaction S(1)...O(2)
(2.847(2) Å). This value is much lower than the sum of the
van der Waals radii of the oxygen and sulfur atoms (3.32 Å).
Unexpected results were obtained in the attempted
cycloaddition of Nꢀmethylazomethine ylide to 8ꢀROꢀ
quinolines. For instance, reactions of compounds 11 and
12 with sarcosine and paraformaldehyde in boiling toluꢀ
ene gave amine 13 as the major product rather than the
expected pyrrolines 23 (Scheme 5).
C(5)
O(2)
N(2)
C(10)
C(6)
C(12)
C(4)
S(1)
C(16)
C(15)
C(17)
C(9)
C(7)
C(11)
C(13)
C(18)
C(14)
C(8)
C(19)
N(1)
C(1)
C(3)
C(2)
Fig. 1. Molecular structure of compound 18 with atomic disꢀ
placement ellipsoids (p = 50%) (Xꢀray diffraction data).
Table 2. Selected bond lengths and bond angles in the
crystal structures of compounds 18 and 24 (Xꢀray difꢀ
fraction data)
Parameter
Bond
18
24
d/Å
N(1)—C(1)
C(1)—C(2)
C(2)—C(3)
C(3)—C(8)
C(4)—N(2)
C(5)—C(10)
C(5)—N(2)
C(8)—C(9)
C(9)—C(4)
C(6)—C(7)
C(7)—C(11)
C(8)—C(11)
C(9)—C(10)
C(10)—C(6)
N(2)—C(12)
C(6)—N(3)
C(7)—S(1)
C(7)—N(4)
1.315(3)
1.412(3)
1.355(3)
1.413(3)
1.468(3)
1.498(3)
1.469(2)
1.407(3)
1.510(3)
1.379(3)
1.440(3)
1.431(3)
1.361(3)
1.413(3)
1.457(2)
1.468(3)
1.768(2)
1.322(1)
1.410(2)
1.370(1)
1.416(1)
1.470(1)
1.507(1)
1.471(1)
1.418(1)
1.504(1)
1.400(1)
1.459(1)
1.423(1)
1.367(1)
1.417(1)
1.453(1)
1.458(1)
—
Scheme 5
1.377(1)
Angle
/deg
C(1)—N(1)—C(11)
C(1)—C(2)—C(3)
C(3)—C(8)—C(9)
C(4)—C(9)—C(8)
C(4)—N(2)—C(5)
C(4)—N(2)—C(12)
N(2)—C(4)—C(9)
C(5)—N(2)—C(12)
C(5)—C(10)—C(6)
C(6)—C(7)—S(1)
C(7)—C(6)—C(10)
C(7)—S(1)—C(13)
S(1)—C(13)—C(14)
C(7)—N(4)—C(13)
C(13)—N(4)—C(14)
117.8(2)
119.0(2)
123.9(2)
128.7(2)
108.4(2)
114.2(2)
102.0(2)
113.1(2)
130.4(2)
122.4(2)
122.6(2)
101.2(9)
108.0(2)
—
118.21(9)
118.47(9)
122.52(9)
129.31(9)
108.20(8)
114.95(8)
101.92(8)
113.78(8)
130.73(9)
—
R = Me, Ph
i. PhMe, 110 C.
In addition, adduct 24 was obtained in minor amounts
(3%); its structure was confirmed by NMR spectroscopy
and Xꢀray diffraction (Fig. 2).
The molecular geometry of structure 24 (see Table 2)
in the crystal is similar to that of compound 18: the fiveꢀ
membered ring adopts an envelope conformation with the
N(2) atom deviating by 0.415(2) Å from the plane of the
122.85(9)
—
—
121.99(8)
113.09(8)
—

[3+2] Cycloaddition to 8ꢀRꢀ5,7ꢀdinitroquinolines
Russ.Chem.Bull., Int.Ed., Vol. 62, No. 4, April, 2013
1055
group with the H atoms of the dimethylamino substituent.
In contrast to structure 18, the latter interactions result in
substantial deviations of the exocyclic N atoms in both the
nitro (by 0.300(2) Å) and dimethylamino groups (by
0.245(2) Å) from the plane of their parent sixꢀmembered
ring. This in turn makes the C(6)—N(3) bond in comꢀ
pound 24 longer by 0.010(4) Å than that in compound 18
(1.468(3) against 1.458(1) Å, respectively). The crystal
packing of structure 24 shows the weak contacts N—H...O
and C—H...O as well as fairly strong intermolecular stackꢀ
ing in pairs between the C(2) and C(1) atoms of the quinꢀ
oline rings (C...C, 3.361(3) Å).
O(1)
O(2)
N(3)
C(13)
C(5)
C(10)
C(6)
N(2)
C(4)
C(14)
C(11)
C(9)
C(8)
N(1)
C(1)
C(3)
Reactions of 8ꢀaminoquinolines 14 and 15 with sarcosine
and paraformaldehyde in boiling toluene produce an inꢀ
separable 1 : 1 mixture of pyrrolines 24 and 25 (or 24 and 26);
i.e., as with 8ꢀROꢀquinolines, the expected tricyclic products
25 and 26 are formed together with compound 24 (Scheme 6).
Products 25 and 26 were identified by NMR spectroscopy,
LCꢀMS, and highꢀresolution mass spectrometry.
Interestingly, the conversion of quinoline 13 in a reacꢀ
tion with azomethine ylide 1 was incomplete even when
the starting compound was refluxed with multiple excessꢀ
es of sarcosine and paraformaldehyde for a long period of
time. The yield of pyrroline 24 was 43% (Scheme 7).
C(2)
Fig. 2. Molecular structure of compound 24 with atomic disꢀ
placement ellipsoids (p = 50%) (Xꢀray diffraction data).
carbon atoms; the sum of the angles at the pyramidal N(2)
atom is 336.9(2) . The quinoline framework is also conꢀ
siderably distorted: the angle C(1)—C(2)—C(10)—C(6) is
6.12(4). As in the crystal structure of compound 18, the
nitro group makes an angle with the plane of the quinoline
ring: the torsion angle C(7)—C(6)—N(3)—O(1) (–38.0(2))
is due to steric interactions of the O atom of the nitro
Scheme 7
Scheme 6
i. PhMe, 110 C.
We found that replacement of an aliphatic amine by an
aromatic one substantially affects the course and pathway
of the cycloaddition. For instance, a reaction of amine 16
with sarcosine and paraformaldehyde under standard conꢀ
ditions (toluene, 110 C) gives, immediately after the comꢀ
plete consumption of the starting compound, adduct 27
and its aromatization products 28 and 29 (Scheme 8),
which were isolated and identified. However, reflux of the
same reaction mixture for 144 h leads to a different ratio of
these three products (Table 3).
To sum up, using 1,3ꢀdipolar cycloaddition reactions
of Nꢀmethylazomethine ylide with substituted 5,7ꢀdinitꢀ
roquinolines, we obtained new derivatives of dihydroisoinꢀ
dole and isoindole fused to the pyridine ring. We also found
that the substituents in the benzene ring affect the cycloꢀ
addition outcome.
X = CH2 (14, 25), O (15, 26)
i. PhMe, 110 C.

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Russ.Chem.Bull., Int.Ed., Vol. 62, No. 4, April, 2013
Bastrakov et al.
Scheme 8
i. PhMe, 110 C.
Table 3. Reaction times of the cycloaddition to comꢀ
pound 16 and the yields of the products
Synthesis of compounds 5—10 (general procedure). An approꢀ
priate thiol (1 mmol) and Et3N (0.1 g, 1 mmol) were added to
a solution of 8ꢀchloroꢀ5,7ꢀdinitroquinoline (4) (0.25 g, 1 mmol)
in dimethoxyethane (50 mL). The reaction mixture was stirred
at room temperature for 0.5—2 h until the starting compound
was completely consumed (monitoring by TLC) and poured into
a 1 : 1 mixture of water and HCl (250 mL). The precipitate that
formed was filtered off, washed with water to a neutral reaction,
and dried in air. Oily products were extracted with ethyl acetate
(2×50 mL), and the extracts were dried with Na2SO4 and conꢀ
centrated.
Reaction
time
Yields of the products (%)
27
28
29
6 h
144 h
59
3
33
67
4
15
In conclusion, it is worth noting that 1,3ꢀdipolar cycloꢀ
addition to the C=N bond of the pyridine ring should not
be ruled out because cycloaddition to this bond of some
azines has been reported.12,13 However, we never observed
this process in our experiments under discussion.
5,7ꢀDinitroꢀ8ꢀ(phenylthio)quinoline (5). Yield 0.29 g (88%),
orange crystals, m.p. 153—155 C. Found (%): C, 55.23; H, 2.91;
N, 12.67; S, 9.93. C15H9N3O4S. Calculated (%): C, 55.04;
H, 2.77; N, 12.84; S, 9.80. 1H NMR (DMSOꢀd6), : 7.27—7.44
(m, 5 H, Ph); 7.96 (dd, 1 H, J1 = 8.7 Hz, J2 = 3.9 Hz); 8.88
(s, 1 H); 8.95 (d, 1 H, J = 8.7 Hz); 9.10 (d, 1 H, J1 = 3.7 Hz).
13C NMR (DMSOꢀd6), : 120.16, 121.61, 126.48, 128.19, 129.36,
130.79, 132.64, 132.78, 138.52, 144.08, 145.90, 148.48, 152.66.
8ꢀBenzylthioꢀ5,7ꢀdinitroquinoline (6). Yield 0.29 g (86%),
yellow crystals, m.p. 132—134 C. Found (%): C, 56.23; H, 3.14;
N, 12.47; S, 9.48. C16H11N3O4S. Calculated (%): C, 56.30;
H, 3.25; N, 12.31; S, 9.39. 1H NMR (DMSOꢀd6), : 4.65 (s, 2 H,
CH2); 6.98—7.35 (m, 5 H, Ph); 8.02 (dd, 1 H, J1 = 8.9 Hz,
J2 = 4.1 Hz); 8.82 (s, 1 H); 8.95 (d, 1 H, J = 8.7 Hz); 9.33
(d, 1 H, J = 3.4 Hz). 13C NMR (DMSOꢀd6), : 40.22, 118.70,
121.56, 126.20, 127.41, 128.40, 128.79, 132.93, 136.90, 138.69,
144.13, 146.60, 149.92, 152.62.
8ꢀFurfurylthioꢀ5,7ꢀdinitroquinoline (7). Yield 0.25 g (74%),
yellowꢀgreen crystals, m.p. 111—113 C. Found (%): C, 50.68;
H, 2.65; N, 12.61; S, 9.43. C14H9N3O5S. Calculated (%): C, 50.75;
H, 2.74; N, 12.68; S, 9.68. 1H NMR (DMSOꢀd6), : 4.75 (s, 2 H,
CH2); 5.86 (s, 1 H); 6.20 (s, 1 H); 7.44 (s, 1 H); 8.03 (dd, 1 H,
J1 = 8.8 Hz, J2 = 4.0 Hz); 8.86 (s, 1 H); 8.97 (d, 1 H, J = 8.6 Hz);
9.32 (d, 1 H, J = 3.3 Hz). 13C NMR (DMSOꢀd6), : 32.68,
108.51, 110.52, 118.62, 121.61, 126.18, 133.00, 137.77, 143.09,
144.49, 146.56, 149.92, 150.39, 152.73.
Experimental
1
H and 13C NMR spectra were recorded on Bruker ACꢀ200
(200 (1H) and 50 MHz (13C)) and Bruker AMꢀ300 instruments
(300 (1H) and 75 MHz (13C)) in DMSOꢀd6 or CDCl3. All experꢀ
iments were performed according to Bruker standard procedures.
Chemical shifts  are referenced to Me4Si. LCꢀMS spectra were
recorded on an Agilent 1200 Series highꢀefficiency liquid chroꢀ
matograph fitted with a Maxis massꢀselective detector (Bruker);
for liquid chromatography, acetonitrile—(H2O + CF3COOH)
(90 : 10) was used as an eluent. Highꢀresolution mass spectra
were measured on a Bruker maXis instrument (ESI, positive ion
detection, capillary voltage 4500 V)14 for an m/z scan range of
50—3000 Da. The instrument was calibrated externally using an
Electrospray Calibrant Solution (Fluka). Samples were dissolved
in acetonitrile and infused through a syringe into the mass
spectrometer at a flow rate of 3 L min–1. Nitrogen was emꢀ
ployed as a nebulizing gas (4 L min–1); the interface temperature
was 180 C. Mass spectra were recorded on an MSꢀKratos inꢀ
strument (EI, 70 eV). The course of the reactions was monitored
and the purity of the products was checked by TLC on Silufol
UVꢀ254 plates. Dry DMF was used; other solvents were not
dried. Compounds 3 (see Refs 6, 7) and 13—15 (see Refs 8, 11)
were prepared as described earlier.
8ꢀCyclohexylthioꢀ5,7ꢀdinitroquinoline (8). Yield 0.28 g (83%),
yellow crystals, m.p. 138—140 C. Found (%): C, 54.12; H, 4.58;
N, 12.69; S, 9.73. C15H15N3O4S. Calculated (%): C, 54.04;
H, 4.54; N, 12.60; S, 9.62. 1H NMR (DMSOꢀd6), : 1.08—1.80
(m, 10 H); 3.99—4.37 (m, 1 H, CH); 8.00 (dd, 1 H, J1 = 8.8 Hz,
J2 = 4.0 Hz); 8.92—8.97 (m, 2 H); 9.28 (d, 1 H, J = 3.2 Hz).

[3+2] Cycloaddition to 8ꢀRꢀ5,7ꢀdinitroquinolines
Russ.Chem.Bull., Int.Ed., Vol. 62, No. 4, April, 2013
1057
13C NMR (DMSOꢀd6), : 24.91, 25.04, 41.91, 118.39, 121.43,
126.04, 132.99, 136.39, 144.72, 146.92, 151.28, 152.82.
Synthesis of compounds 17—22 and 24—29 (general proceꢀ
dure). A mixture of an appropriate 8ꢀRꢀ5,7ꢀdinitroquinoline
(1 mmol), paraformaldehyde (1 mmol), and sarcosine (1 mmol)
was refluxed in toluene (30 mL), while adding paraformaldehyde
(1 mmol) and sarcosine (1 mmol) every hour until the starting
compound was completely consumed. After the reaction was
completed, the reaction mixture was cooled and concentrated
in vacuo. The residue was separated by column chromatography
on SiO2 with CHCl3 or CHCl3—MeOH (10 : 1) as eluents.
2ꢀMethylꢀ4ꢀnitroꢀ5ꢀphenylthioꢀ2,3ꢀdihydroꢀ1Hꢀpyrroloꢀ
[3,4ꢀf]quinoline (17). Yield 0.12 g (35%), yellow crystals, m.p.
182—185 C (THF). Found (%): C, 64.13; H, 4.56; N, 12.61;
S, 9.43. C18H15N3O2S. Calculated (%): C, 64.08; H, 4.48; N, 12.45;
8ꢀ(4ꢀChlorophenylthio)ꢀ5,7ꢀdinitroquinoline (9). Yield 0.21 g
(58%), orange crystals, m.p. 150—152 C (EtOH). Found (%):
C, 49.67; H, 2.41; N, 11.67; S, 8.93. C15H8ClN3O4S. Calculatꢀ
ed (%): C, 49.80; H, 2.23; N, 11.62; S, 8.86. 1H NMR (DMSOꢀd6),
: 7.35 (s, 4 H, Ph); 7.96 (dd, 1 H, J1 = 8.8 Hz, J2 = 4.0 Hz);
8.86—9.02 (m, 2 H); 9.09 (d, 1 H, J = 2.7 Hz). 13C NMR
(DMSOꢀd6), : 120.01, 121.75, 126.51, 129.26, 132.08, 132.41,
132.81, 137.74, 144.40, 145.78, 148.71, 152.72.
Methyl 2ꢀ[(5,7ꢀdinitroquinolinꢀ8ꢀyl)sulfanyl]acetate (10).
Yield 0.2 g (63%), yellow crystals, m.p. 110—113 C. Found (%):
C, 44.42; H, 2.93; N, 12.87; S, 9.93. C12H9N3O6S. Calculatꢀ
ed (%): C, 44.58; H, 2.81; N, 13.00; S, 9.92. 1H NMR (DMSOꢀd6),
: 3.55 (s, 3 H, Me); 4.29 (s, 2 H, CH2); 8.00 (dd, 1 H, J1 = 8.6 Hz,
J2 = 3.7 Hz); 8.85—9.04 (m, 2 H); 9.17 (d, 1 H, J = 2.8 Hz).
13C NMR (DMSOꢀd6), : 52.25, 138.99, 139.58, 143.92, 144.10,
146.17, 149.29, 152.12, 169.13, 169.88.
5,7ꢀDinitroꢀ8ꢀphenoxyquinoline (11). Phenol (0.372 g, 4 mmol)
and Na2CO3 (0.42 g, 4 mmol) were added to a solution of dinitroꢀ
quinoline 4 (1 g, 4 mmol) in acetonitrile (50 mL). The reaction
mixture was refluxed for 2 h until the starting compound was
completely consumed (monitoring by TLC), poured into a fiveꢀ
fold excess of water, and acidified with HCl to pH 1—2. The
precipitate that formed was filtered off and washed with water to
a neutral reaction. Yield 1.1 g (89%), white crystals, m.p.
127—130 C. Found (%): C, 57.94; H, 2.96; N, 13.46. C15H9N3O5.
Calculated (%): C, 57.88; H, 2.91; N, 13.50. 1H NMR (DMSOꢀd6),
: 6.93—7.35 (m, 5 H, Ph); 7.96 (dd, 1 H, J1 = 8.6 Hz, J2 = 3.7 Hz);
8.84—9.10 (m, 3 H). 13C NMR (DMSOꢀd6), : 115.72, 120.66,
122.96, 124.37, 126.71, 129.71, 132.58, 137.42, 140.47, 141.59,
141.79, 148.55, 153.03, 158.78.
8ꢀMethoxyꢀ5,7ꢀdinitroquinoline (12). A 2 M solution of
MeONa (4 mmol) in MeOH (2 mL) was added to a solution of
dinitroquinoline 4 (0.5 g, 2 mmol) in methanol (30 mL). The
reaction mixture was refluxed for 1.5 h until the starting comꢀ
pound was completely consumed (monitoring by TLC), poured
into a fiveꢀfold excess of water, and acidified with HCl to pH 2.
The precipitate that formed was filtered off and washed with
water to a neutral reaction. Yield 0.5 g (99%), white crystals,
m.p. 149—151 C. Found (%): C, 48.24; H, 2.71; N, 16.81.
C10H7N3O5. Calculated (%): C, 48.20; H, 2.83; N, 16.68.
1H NMR (DMSOꢀd6), : 4.42 (s, 3 H, CH3); 8.00 (dd, 1 H,
J1 = 8.6 Hz, J2 = 3.7 Hz); 8.83—9.06 (m, 2 H); 9.18 (d, 1 H,
J = 2.7 Hz). 13C NMR (DMSOꢀd6), : 64.96, 120.61, 123.92,
126.36, 132.55, 139.28, 141.74, 151.80, 154.4.
1
S, 9.50. H NMR (CDCl3), : 2.70 (s, 3 H, Me); 4.20 (s, 2 H,
CH2); 4.40 (s, 2 H, CH2); 6.99—7.23 (m, 5 H, Ph); 7.30—7.70
(dd, 1 H, J1 = 8.0 Hz, J2 = 3.9 Hz); 8.05 (d, 1 H, J = 8.6 Hz);
9.03 (d, 1 H, J = 3.3 Hz). 13C NMR (CDCl3), : 59.73, 59.84,
123.07, 124.79, 126.62, 128.64, 129.66, 131.04, 132.68, 135.30,
141.01, 151.69.
5ꢀBenzylthioꢀ2ꢀmethylꢀ4ꢀnitroꢀ2,3ꢀdihydroꢀ1Hꢀpyrrolo[3,4ꢀf]ꢀ
quinoline (18). Yield 0.23 g (65%), red crystals, m.p. 134—138 C.
Found (%): C, 64.91; H, 4.77; N, 12.03; S, 9.17. C19H17N3O2S.
1
Calculated (%): C, 64.94; H, 4.88; N, 11.96; S, 9.12. H NMR
(CDCl3), : 2.66 (s, 3 H, Me); 4.11 (s, 2 H, CH2); 4.33 (s, 2 H,
CH2); 4.38 (s, 2 H, CH2); 7.01—7.17 (m, 5 H, Ph); 7.57 (dd, 1 H,
J1 = 8.2 Hz, J2 = 4.2 Hz); 8.06 (d, 1 H, J = 8.2 Hz); 9.12—9.18
(m, 1 H). 13C NMR (CDCl3), : 40.75, 42.09, 59.69, 59.77,
122.90, 124.64, 126.78, 127.12, 128.20, 128.83, 130.62, 133.04,
137.13, 140.37, 147.61, 151.27.
5ꢀCyclohexylthioꢀ2ꢀmethylꢀ4ꢀnitroꢀ2,3ꢀdihydroꢀ1Hꢀpyrroꢀ
lo[3,4ꢀf]quinoline (19). Yield 0.2 g (58%), yellow crystals, m.p.
189—192 C. Found (%): C, 62.87; H, 6.31; N, 12.11; S, 9.33.
C18H21N3O2S. Calculated (%): C, 62.95; H, 6.16; N, 12.23;
S, 9.34. 1H NMR (CDCl3), : 1.00—1.89 (m, 10 H); 2.67 (s, 3 H,
Me); 3.61—3.83 (m, 1 H, CH); 4.14 (s, 2 H, CH2); 4.35 (s, 2 H,
CH2); 7.55 (dd, 1 H, J1 = 8.3 Hz, J2 = 4.2 Hz); 8.05 (d, 1 H,
J = 7.3 Hz); 9.11 (d, 1 H, J = 2.4 Hz). 13C NMR (CDCl3),
: 25.42, 25.67, 33.05, 42.09, 47.65, 59.58, 59.70, 122.77, 124.43,
126.11, 130.25, 132.91, 140.11, 147.82, 150.70, 151.23.
5ꢀFurfurylthioꢀ2ꢀmethylꢀ4ꢀnitroꢀ2,3ꢀdihydroꢀ1Hꢀpyrroloꢀ
[3,4ꢀf]quinoline (20). Yield 0.15 g (43%), yellowꢀbrown crystals,
m.p. 180—182 C (THF). Found (%): C, 59.68; H, 4.56; N, 12.51;
S, 9.23. C17H15N3O3S. Calculated (%): C, 59.81; H, 4.43;
N, 12.31; S, 9.39. 1H NMR (CDCl3), : 2.68 (s, 3 H, Me); 4.14
(s, 2 H, CH2); 4.29—4.48 (m, 4 H, 2 CH2); 5.68 (s, 1 H); 6.07
(s, 1 H); 7.19 (s, 1 H); 7.57 (dd, 1 H, J1 = 8.0 Hz, J2 = 3.6 Hz); 8.07
(d, 1 H, J = 8.0 Hz); 9.13 (d, 1 H, J = 3.5 Hz). 13C NMR
(CDCl3), : 32.79, 42.01, 59.62, 59.71, 107.77, 110.08, 122.85,
124.59, 126.16, 130.55, 133.03, 140.52, 142.11, 143.89, 147.41,
150.28, 151.27.
8ꢀ[(4ꢀChlorophenyl)amino]ꢀ5,7ꢀdinitroquinoline
(16).
4ꢀChloroaniline (0.25 g, 2 mmol) was added to a solution of
quinoline 4 (0.25 g, 1 mmol) in ethanol (50 mL). The reacꢀ
tion mixture was stirred at room temperature for 2.5 h (moniꢀ
toring by TLC), poured into a fiveꢀfold excess of water, and
acidified with HCl to pH 1—2. The precipitate that formed
was filtered off and washed with water to a neutral reaction.
Yield 0.28 g (80%), orange crystals, m.p. 172—174 C. Found (%):
C, 52.37; H, 2.71; N, 16.12. C15H9ClN4O4. Calculated (%):
C, 52.26; H, 2.63; N, 16.25. 1H NMR (DMSOꢀd6), : 7.16—7.48
(m, 4 H, C6H4); 8.01 (dd, 1 H, J1 = 8.6 Hz, J2 = 2.8 Hz); 8.9
(s, 1 H); 9.07 (d, 1 H, J = 2.7 Hz); 9.18 (d, 1 H, J = 8.6 Hz);
10.85 (s, 1 H, NH). 13C NMR (DMSOꢀd6), : 122.46,
125.22, 127.17, 128.86, 129.28, 132.72, 133.12, 138.82, 139.92,
141.24, 149.73.
5ꢀ[(4ꢀChlorophenyl)thio]ꢀ2ꢀmethylꢀ4ꢀnitroꢀ2,3ꢀdihydroꢀ1Hꢀ
pyrrolo[3,4ꢀf]quinoline (21a). Yield 0.11 g (30%), yellow crysꢀ
tals, m.p. 196—198 C (EtOH). Found (%): C, 58.19; H, 3.88;
N, 11.45; S, 8.71. C18H14ClN3O2S. Calculated (%): C, 58.14;
1
H, 3.79; N, 11.30; S, 8.62. H NMR (CDCl3), : 2.71 (s, 3 H,
Me); 4.21 (s, 2 H, CH2); 4.41 (s, 2 H, CH2); 7.10—7.25 (m, 4 H,
C6H4); 7.56 (dd, 1 H, J1 = 8.3 Hz, J2 = 4.2 Hz); 8.08 (dd, 1 H,
J1 = 8.3 Hz, J2 = 1.4 Hz); 9.04 (dd, 1 H, J1 = 4.2 Hz, J2 = 1.4 Hz).
Methyl 2ꢀ[(2ꢀmethylꢀ4ꢀnitroꢀ2,3ꢀdihydroꢀ1Hꢀpyrrolo[3,4ꢀf]ꢀ
quinolinꢀ5ꢀyl)sulfanyl]acetate (21b). Yield 0.09 g (27%), yellow
crystals, m.p. 135—139 C. Found (%): C, 54.08; H, 4.48;

1058
Russ.Chem.Bull., Int.Ed., Vol. 62, No. 4, April, 2013
Bastrakov et al.
N, 12.69; S, 9.43. C15H15N3O4S. Calculated (%): C, 54.04;
H, 4.54; N, 12.60; S, 9.62. H NMR (CDCl3), : 2.71 (s, 3 H,
6.96 (d, 2 H, C6H4, J = 8.7 Hz); 7.16—7.35 (m, 2 H, C6H4);
7.6 (dd, 1 H, J1 = 8.3 Hz, J2 = 4.2 Hz); 8.01 (dd, 1 H, J1 = 8.3 Hz,
J2 = 1.4 Hz); 8.83 (dd, 1 H, J1 = 4.3 Hz, J2 = 1.6 Hz); 9.06
(s, 1 H, NH). 13C NMR (CDCl3), : 42.49, 59.44, 62.80, 120.36,
124.37, 125.68, 126.97, 128.85, 129.01, 129.21, 132.72, 133.36,
135.04, 139.66, 140.66, 148.19. MS, m/z: 354 [M]+.
1
Me); 3.63 (s, 3 H, CH3); 3.96 (s, 2 H, CH2); 4.22 (s, 2 H, CH2);
4.38 (s, 2 H, CH2); 7.6 (dd, 1 H, J1 = 8.3 Hz, J2 = 4.2 Hz); 8.11
(dd, 1 H, J1 = 8.7 Hz, J2 = 1.7 Hz); 9.09—9.15 (m, 1 H).
13C NMR (CDCl3), : 37.55, 42.32, 52.49, 59.97, 60.17, 123.24,
125.06, 125.99, 131.17, 133.42, 141.24, 147.31, 150.31, 151.47,
169.71. MS, m/z: 334 [M]+.
5ꢀ[(4ꢀChlorophenyl)thio]ꢀ2ꢀmethylꢀ4ꢀnitroꢀ2Hꢀpyrrolo[3,4ꢀf]ꢀ
quinoline (22a). Yield 0.026 g (7%), red crystals, m.p. 240—243 C
(EtOH). Found (%): C, 58.42; H, 3.34; N, 11.45; S, 8.54.
C18H12ClN3O2S. Calculated (%): C, 58.46; H, 3.27; N, 11.36;
S, 8.67. 1H NMR (CDCl3), : 4.07 (s, 3 H, Me); 7.08—7.25
(m, 5 H); 7.41—7.52 (m, 1 H); 7.60 (s, 1 H, CH); 8.35 (d, 1 H,
J = 7.6 Hz); 8.76—8.85 (m, 1 H).
Methyl 2ꢀ[(2ꢀmethylꢀ4ꢀnitroꢀ2Hꢀpyrrolo[3,4ꢀf]quinolinꢀ5ꢀ
yl)sulfanyl]acetate (22b). Yield 0.05 g (15%), red crystals, m.p.
198—202 C (THF). Found (%): C, 54.46; H, 3.87; N, 12.61;
S, 9.74. C15H13N3O4S. Calculated (%): C, 54.37; H, 3.95; N, 12.68;
S, 9.68. 1H NMR (CDCl3), : 3.64 (s, 3 H, Me); 3.9 (s, 2 H,
CH2); 4.04 (s, 3 H, CH3); 7.23 (d, 1 H, J = 1.0 Hz); 7.46—7.54
(m, 1 H); 7.57 (d, 1 H, J = 2.1 Hz); 8.36 (dd, 1 H, J1 = 8 Hz,
J2 = 1.7 Hz); 8.91 (dd, 1 H, J1 = 4.2 Hz, J2 = 1.4 Hz). MS, m/z:
331 [M]+.
5ꢀ[(4ꢀChlorophenyl)amino]ꢀ2ꢀmethylꢀ4ꢀnitroꢀ2Hꢀpyrroloꢀ
[3,4ꢀf]quinoline (29). Yield 0.05 g (15%), red crystals, m.p.
211—215 C. Found (%): C, 61.36; H, 3.86; N, 15.83. C18H13N4O2.
Calculated (%): C, 61.28; H, 3.71; N, 15.88. 1H NMR (CDCl3),
: 4.00 (s, 3 H, Me); 6.98 (d, 2 H, J = 7.6 Hz); 7.24—7.35 (m, 2 H);
7.46—7.65 (m, 3 H); 8.31 (d, 1 H, J = 8.0 Hz); 8.65 (d, 1 H,
J = 4.5 Hz); 9.84 (s, NH). 13C NMR (CDCl3), : 41.45, 43.73,
63.05, 67.41, 92.40, 122.61, 123.23, 126.37, 128.95, 129.04,
130.49, 136.36, 138.51, 138.69, 145.38, 150.18. MS, m/z: 352 [M]+.
Xꢀray diffraction studies of compounds 18 and 24 were carꢀ
ried out on Bruker SMART 1000 CCD and Bruker Apex II
diffractometers, respectively (MoꢀK radiation, graphite monoꢀ
chromator,  scan mode). The structures were solved by the
direct methods and refined anisotropically on F2 by the fullꢀ
hkl
matrix leastꢀsquares method. The hydrogen atoms were located
geometrically; their coordinates and thermal parameters were
refined using a riding model with fixed idealized C—H bond
lengths. Crystallographic parameters and the data collection
and refinement statistics are summarized in Table 4. All calꢀ
5ꢀDimethylaminoꢀ2ꢀmethylꢀ4ꢀnitroꢀ2,3ꢀdihydroꢀ1Hꢀpyrroloꢀ
[3,4ꢀf]quinoline (24). Yield 0.12 g (43%), red crystals, m.p.
122—125 C. Found (%): C, 61.83; H, 5.87; N, 20.57. C14H16N4O2.
Calculated (%): C, 61.75; H, 5.92; N, 20.58. 1H NMR (CDCl3),
: 2.68 (s, 3 H, Me); 3.16 (s, 6 H, NMe2); 4.22 (s, 2 H, CH2);
4.28 (s, 2 H, CH2); 7.50 (dd, 1 H, J1 = 8.3 Hz, J2 = 4.0 Hz); 7.96
(dd, 1 H, J1 = 8.3 Hz, J2 = 1.7 Hz); 8.96 (d, 1 H, J1 = 4.0 Hz).
HRMS: found m/z 273.1351; C14H17N4O2; calculated 273.1346.
2ꢀMethylꢀ4ꢀnitroꢀ5ꢀpiperidinoꢀ2,3ꢀdihydroꢀ1Hꢀpyrrolo[3,4ꢀf]ꢀ
quinoline (25). 1H NMR (CDCl3), : 1.56—1.89 (m, 6 H); 2.60
(s, 3 H, NMe); 3.22—3.41 (m, 4 H); 4.08—4.23 (m, 4 H);
7.34—7.46 (m, 1 H); 7.81—7.91 (m, 1 H); 8.82—8.90 (m, 1 H).
HRMS: found m/z 313.1662; C17H21N4O2; calculated 313.1659.
2ꢀMethylꢀ5ꢀmorpholinoꢀ4ꢀnitroꢀ2,3ꢀdihydroꢀ1Hꢀpyrroloꢀ
Table 4. Crystallographic parameters and the data collection and
refinement statistics for structures 18 and 24
Parameter
18
24
Molecular formula
Molecular weight
T/K
C19H17N3O2S
351.42
120
C14H16N4O2
272.31
100
Crystal system
Space group
Z2
Triclinic
Triclinic
P–1
P–1
2
1
[3,4ꢀf]quinoline (26). H NMR (CDCl3), : 2.67 (s, 3 H, Me);
a/Å
b/Å
c/Å
/deg
/deg
/deg
8.038(1)
8.913(1)
12.782(2)
79.822(2)
78.543(2)
67.736(2)
825.3(2)
1.414
8.0409(4)
9.3294(5)
9.8592(5)
103.495(1)
113.479(1)
96.054(1)
643.11(6)
1.406
3.48 (t, 4 H, J = 4.5 Hz); 3.88 (t, 4 H, J = 4.5 Hz); 4.20 (s, 2 H,
CH2); 4.30 (s, 2 H, CH2); 7.45—7.51 (m, 1 H); 7.93—8.02 (m, 1 H);
8.92—8.95 (m, 1 H). HRMS: found m/z 315.1453; C16H18N4O3;
calculated 315.1452.
5ꢀ[(4ꢀChlorophenyl)amino]ꢀ2ꢀmethylꢀ4,9bꢀdinitroꢀ2,3,3a,
9bꢀtetrahydroꢀ1Hꢀpyrrolo[3,4ꢀf]quinoline (27). Yield 0.24 g
(59%), orange crystals, m.p. 183—186 C. Found (%): C, 53.72;
H, 4.12; N, 17.40. C18H16ClN5O4. Calculated (%): C, 53.81;
3
V/Å
dcalc/g cm–3
/cm–1
2.14
0.98
1
H, 4.01; N, 17.43. H NMR (CDCl3), : 2.4 (s, 3 H, Me); 2.48
F(000)
368
288
(t, 1 H, J = 9.0 Hz); 3.13 (d, 1 H, J = 8.7 Hz); 3.71 (t, 1 H,
J = 8.7 Hz); 4.18 (d, 1 H, J = 11.1 Hz); 4.78 (t, 1 H, J = 8.2 Hz);
6.88 (d, 2 H, C6H4, J = 8.7 Hz); 7.24—7.34 (m, 2 H, C6H4); 7.53
(dd, 1 H, J1 = 8 Hz, J2 = 4.5 Hz); 8.02 (d, 1 H, J = 8.0 Hz); 8.64
(d, 1 H, J = 4.5 Hz); 10.26 (s, 1 H, NH). 13C NMR (CDCl3),
: 41.45, 43.74, 63.05, 67.41, 92.41, 122.61, 123.23, 126.38,
128.95, 129.04, 130.49, 136.37, 138.51, 138.69, 145.39, 150.18.
MS, m/z: 401 [M]+.
5ꢀ[(4ꢀChlorophenyl)amino]ꢀ2ꢀmethylꢀ4ꢀnitroꢀ2,3ꢀdihydroꢀ
1Hꢀpyrrolo[3,4ꢀf]quinoline (28). Yield 0.24 g (67%), red crysꢀ
tals, m.p. 192—195 C. Found (%): C, 60.83; H, 4.00; N, 15.72.
C18H15ClN4O2. Calculated (%): C, 60.94; H, 4.26; N, 15.79.
1H NMR (CDCl3), : 2.97 (s, 3 H, Me); 4.29 (s, 2 H); 4.38 (s, 2 H);
2max/deg
56
60
Number of measured
/unique reflections
Number of reflections
with I > 2(I)
Number of
parameters refined
R1
8494/3974
8353/3721
2468
227
3264
184
0.0479
0.0933
1.059
0.0372
0.0856
1.031
wR2
GOOF
Residual electron density, 0.321/–0.344
e Å–3(dmax/dmin
0.416/–0.241
)

[3+2] Cycloaddition to 8ꢀRꢀ5,7ꢀdinitroquinolines
Russ.Chem.Bull., Int.Ed., Vol. 62, No. 4, April, 2013
1059
culations were performed with the SHELX program package
(version 2009ꢀ9.1).15
5. L. N. Yakhontov, R. G. Glushkov, Sinteticheskie lekarstꢀ
vennye sredstva [Synthetic Drugs], Meditsina, Moscow, 1983,
p. 272 (in Russian).
We are grateful to the collaborators of the Structural
Research Department of the N. D. Zelinsky Institute of
Organic Chemistry of the Russian Academy of Sciences
(Moscow) for measuring highꢀresolution mass spectra.
This work was financially supported by the Russian
Foundation for Basic Research (Project Nos 12ꢀ03ꢀ31352
mol_a, 13ꢀ03ꢀ00452a, and 12ꢀ03ꢀ31655 mol_a) and the
Council on Grants at the President of the Russian Federaꢀ
tion (State Support Program for Young Russian Ph.D.
Scientists, Grant MKꢀ3599.2013.3).
6. R. P. Dikshoorn, Rec. Trav. Chim., 1929, 48, 550.
7. N. L. Khilkova, V. N. Knyazev, N. S. Patalakha, V. N.
Drozd, Russ. J. Org. Chem. (Engl. Transl.), 1992, 28 [Zh. Org.
Khim., 1992, 28, 1048].
8. H. Hennig, J. Tauchnitz, K. Schöne, Z. Chem., 1971, 11, 267.
9. V. N. Drozd, V. N. Knyazev, N. L. Khilkova, D. S. Yufit,
Yu. T. Struchkov, I. V. Stankevich, A. L. Chistyakov, Zh. Org.
Khim., 1993, 29, 770 [Russ. J. Org. Chem. (Engl. Transl.),
1993, 29].
10. V. N. Knyazev, Zh. Org. Khim., 1994, 30, 94 [Russ. J. Org.
Chem. (Engl. Transl.), 1994, 30].
11. I. G. Il´ina, V. V. Mel´nikov, M. N. Tarasevich, K. P. Butin,
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Received December 27, 2012;
in revised form February 21, 2013