Dearomative (3+2) cycloaddition of 2-substituted 3,5-dinitropyridines and N-methyl azomethine ylide

Article abstract of DOI:10.1007/s10593-019-02421-9

[Figure not available: see fulltext.] 1,3-Dipolar cycloaddition of various 2-substituted 3,5-dinitropyridines and unstabilized N-methyl azomethine ylide has been studied. It was found that, depending on the nature of the substituent, the reaction results

Full text of DOI:10.1007/s10593-019-02421-9

DOI 10.1007/s10593-019-02421-9
Chemistry of Heterocyclic Compounds 2019, 55(1), 72–77
Dearomative (3+2) cycloaddition of 2-substituted 3,5-dinitropyridines
and N-methyl azomethine ylide
Maxim A. Bastrakov1*, Alexey K. Fedorenko1, Alexey M. Starosotnikov1,
Vadim V. Kachala1, Svyatoslav A. Shevelev1
1 N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky Ave., Moscow 119991, Russia; е-mail: b_max82@mail.ru
Published in Khimiya Geterotsiklicheskikh Soedinenii,
2019, 55(1), 72–77
Submitted November 7, 2018
Accepted December 12, 2018
Me
R = SAlk, SAr, OAlk, OAr
N
O2N
O2N
NO2
R
Me
N
Me
N
N
N
N
O2N
NO2
R
H2C
CH2
Me
N
Me
N
N
O2N
R = NR1R2
NO2
+
Me
R1
R1
R1 = R2 = Alk
N
N
N
R1 = Me, R2 = Ph
R2
R2
1,3-Dipolar cycloaddition of various 2-substituted 3,5-dinitropyridines and unstabilized N-methyl azomethine ylide has been studied.
It was found that, depending on the nature of the substituent, the reaction results in addition of one or two equivalents of 1,3-dipole to the
pyridine ring. Eventually, a convenient method for the synthesis of differently substituted heterocyclic systems containing one or two
pyrrolidine fragments fused with a pyridine ring has been demonstrated.
Keywords: azomethine ylide, pyridine, pyrrolidine, dearomatization, 1,3-dipolar cycloaddition.
Dearomatization of (het)arenes is one of the most conve-
nient strategies for the synthesis of bioactive molecules and
natural products.1 Over the last few decades, application of
this approach has significantly increased.1c,e,2 Different
types of reactions have been used for the formation of new
carbon–carbon and carbon–heteroatom bonds in the synthesis
of biologically active compounds.2,3 Among the various
dearomatization strategies, (3+2) cycloaddition reactions
have attracted considerable interest. Recently, 1,3-dipolar
cycloadditions of C=C bonds of (hetero)aromatic com-
pounds and unstabilized azomethine ylides have been
reported.4 In addition, our previous studies have shown that
different aromatic nitro compounds 1a–g may be exploited
in 1,3-dipolar cycloaddition reaction with azomethine ylide
2 to give polycyclic products 3a–g (Scheme 1).5
Pyridines are important nitrogen heterocycles that are
incorporated in a wide range of natural compounds and
have been also extensively used in pharmaceutical industry.
A large number of pyridine derivatives possess anti-
microbial, antiviral, anticancer, analgesic, antioxidant, and
many other activities.6 Furthermore, these heterocyclic
Scheme 1
Me
Me
N
N
N
NO2
NO2
N
H2C
CH2
H
2
O2N
N
PhMe
110°C, 2 h
24–69%
O2N
H
1a g
Me
3a g
N
N
N
N
=
S
N,
,
,
,
N Me
Se
N
N
N
N
Ph
a
b
c
d
N
S
O
,
,
N
N
e
f
g
compounds have been used as dyes, agrochemicals, poly-
mers, and reagents or catalysts in organic synthesis.6b Due
to the many important applications of pyridines, advanced
methodologies for obtaining their derivatives are currently
in demand.
0009-3122/19/55(1)-0072©2019 Springer Science+Business Media, LLC
72

Chemistry of Heterocyclic Compounds 2019, 55(1), 000–000
Table 1. Synthesis of compounds 8a–o
In 2013, Lee et al. reported 1,3-dipolar cycloaddition of
under different reaction conditions
3,5-dinitropyridine (4) and N-benzyl azomethine ylide 5 to
produce polycyclic compound 6 (Scheme 2).4c At the same
time, similar interactions of reactant 5 and 3-nitropyridine
or its N-oxide were unsuccessful. The 1,3-dipolar cyclo-
addition of compounds 4 and 5 is a single example of such
reactions of pyridine derivatives described in literature.
Recently, we demonstrated previously unreported (3+2) cyclo-
addition of several 2-substituted 3,5-dinitropyridines and
N-methyl azomethine ylide 2.7 In all cases, double
cycloaddition of the 1,3-dipole afforded a novel tricyclic
heterosystem – 1,2,3,3a,5a,6,7,8,8a,8b-decahydrodipyrrolo-
[3,4-b:3',4'-d]pyridine. Herein, we report the influence of
the substituent at the C-2 atom of 3,5-dihydropyridine on
this reaction.
Product
8a
8b
RH
PhSH
BnSH
Reaction conditions*
Yield, %
94**
83
i
i
i
87**
8c
HSCH2CO2Me
i
i
90
8d
8e
83**
i-BuSH
PhOH
4-ClC6H4OH
4-O2NC6H4OH
i
81**
93**
96
8f
8g
8h
8i
Scheme 2
ii
ii
ii
Bn
N
Bn
N
83
H2C
CH2
O2N
O2N
NO2
5
NO2
Bn
N
i
77
8j
CH2Cl2, rt, 1 h
72%
N
N
N
4
Et2NH
PhNHMe
iii
i
79
95
8k
8l
Bn
6
Commercially available 2-chloro-3,5-dinitropyridine (7)
was used as a starting compound for the synthesis of
pyridine derivatives 8a–o, and chlorine atom was readily
substituted with various nucleophiles (Table 1).
Pyridines 8a–o were further studied in 1,3-dipolar
cycloaddition reactions with N-methyl azomethine ylide 2,
which was generated in situ from sarcosine (9) and
paraformaldehyde in PhMe under reflux (Table 2).7 In case
of compounds 8a–i,o, products 10a–i,o resulting from
double cycloaddition of the 1,3-dipole to aromatic
C=C–NO2 fragments were isolated.
The structures of products 10a–i,o were established by
1H and 13C NMR spectroscopy, HRMS data, and X-ray
diffraction studies (for compounds 10a,c,g7). It was found
that addition of two molecules of N-methyl azomethine
ylide 2 occurs from the opposite sides of the pyridine ring.
Similar situation was observed earlier in the case of
m-dinitrobenzo(het)arenes.5a Furthermore, the molecular
structure of compounds 10a,c,g confirmed the anticipated
syn addition of the 1,3-dipole. Thereby, the investigated
cycloaddition proceeds stereoselectively – one diastereo-
mer of product 10a–i,o is solely formed as a racemic
mixture of enantiomers (only one enantiomer for each
product is shown in Table 2).
iii
93
8m
iii
iv
79
93
8n
8o
MeOH
* i: RH (1 equiv), Et3N, MeOH, rt, 0.5–2 h; ii: RH (1 equiv), Na2CO3,
MeCN, Δ, 2 h; iii: RH (2 equiv), MeOH, rt, 2 h; iv: NaOMe, MeOH, Δ, 4 h.
** The synthesis was performed according to previously reported procedure.7
Table 2. Synthesis of compounds 10a–i,o
Product
R
Yield, %
PhS
BnS
68*
52
10a
10b
56*
10c
Unexpected results were obtained when the reaction of
2-substituted 3,5-dinitropyridines 8j–n and azomethine
ylide 2 was performed. It was found that, along with double
SCH2CO2Me
41
10d
10e
50*
cycloadducts
10j–n,
2,3-dihydro-1H-pyrrolo[3,4-c]-
pyridines 11j–n were also formed (Scheme 3). Most likely,
bicyclic intermediate 12 is produced in the first step of the
1,3-dipolar cycloaddition. Thereafter, two competing
reactions are possible: second cycloaddition leading to
1,2,3,3a,5a,6,7,8,8a,8b-decahydrodipyrrolo[3,4-b:3',4'-d]-
pyridines 10j–n or aromatization via elimination of HNO2
to afford products 11j–n. It should be noted that, in the
i-BuS
PhO
38*
45*
64
10f
10g
10h
10i
4-ClC6H4O
4-O2NC6H4O
MeO
53
31
10o
* The synthesis was performed according to previously reported procedure.7
73

Chemistry of Heterocyclic Compounds 2019, 55(1), 000–000
Scheme 3
Table 3. Electron-donating mesomeric effect (+M)
case of starting materials 8k,n, only adducts 11k,n were
of some exemplary substituents8
1
isolated. Although the H NMR spectra of crude products
contained additional signals corresponding to the double
cycloaddition products 10k,n, isolation of these com-
pounds in pure form was unsuccessful, apparently, due to
their low stability.
Substituent
+M effect
Substituent
+M effect
PhS
PhO
MeO
0.23
0.40
0.56
Et2N
PhNH
Me2N
0.73
0.78
0.98
According to the obtained results, influence of the sub-
stituent at the C-2 atom of 3,5-dinitropyridines 8a–o on the
reaction pathway may be clarified. We assume that the key
stage is the formation of intermediate 13 (Scheme 4). In the
case of 3,5-dinitropyridin-2-amines 8j–n, this adduct may also
exist in resonance form 14. Second cycloaddition of 1,3-dipole
2 at C=C–NO2 fragment in intermediate 13 leads to the forma-
tion of products 10a–o, whereas zwitterion 14 promptly
undergoes aromatization by loss of HNO2 to afford 2,3-di-
hydro-1H-pyrrolo[3,4-c]pyridin-4-amines 11j–n. In other
words, the increased electron-donating mesomeric effect (+M)
of amino group may reduce the electrophilicity of C=C(NO2)
bond in intermediate 13 and its reactivity toward nucleo-
philic 1,3-dipoles. The +M effect increases significantly in
substituent row RS < RO < RNH or R1R2N (Table 3).8
The structures of compounds 10a–o and 11j–n were
data. In addition, the regioselectivity of cycloaddition to
afford product 11m was clarified by 2D NMR spectro-
scopy. The NOESY spectrum of adduct 11m contained a
characteristic cross peak corresponding to the interaction of
3-СН2 and 2'-СН protons (Fig. 1). At the same time, if
alternative product 15 was formed, the cross peak
regarding the interaction of 5-СН2 and H-4 protons would
have been expected, which, in fact, was not observed. This
information allowed us to conclude that cycloaddition of
2-substituted 3,5-dinitropyridines 8j–n and N-methyl
azomethine ylide 2 occurs at the С(3a)–С(7a) bond of the
pyridine ring.
In summary, the synthesis of new derivatives of
1,2,3,3a,5a,6,7,8,8a,8b-decahydrodipyrrolo[3,4-b:3',4'-d]-
1
confirmed by H and 13C NMR spectroscopy and HRMS
Scheme 4
Figure 1. Selected characteristic interactions of protons in
NOESY spectrum of compound 11m and expected interaction of
protons in hypothetical product 15.
74

Chemistry of Heterocyclic Compounds 2019, 55(1), 000–000
pyridines and 2,3-dihydro-1H-pyrrolo[3,4-c]pyridines has
2-chloro-3,5-dinitropyridine (7) (611 mg, 3 mmol) in
MeCN (50 ml). The reaction mixture was refluxed for 2 h,
and complete consumption of starting material 7 was
confirmed by TLC (eluent CHCl3). The mixture was then
poured into H2O (250 ml) and acidified with aqueous HCl
to pH 2. The obtained precipitate was filtered off, washed
with H2O (75 ml), and air-dried.
been achieved. The influence of substituent in series of
2-substituted 3,5-dinitropyridines on the 1,3-dipolar cyclo-
addition with N-methyl azomethine ylide has been studied.
An increased electron-donating mesomeric effect (+M) of
the substituent reduces the reactivity of 3,5-dinitropyridines
toward nucleophilic 1,3-dipole and suppresses the second
cycloaddition leading to 2,3-dihydro-1H-pyrrolo[3,4-c]-
pyridines as the main products.
2-(4-Chlorophenoxy)-3,5-dinitropyridine (8h). Yield
1
851 mg (96%), yellow crystals, mp 116–117°С. Н NMR
spectrum, δ, ppm (J, Hz): 7.38 (2H, d, J = 8.4, H Ar); 8.58
(2H, d, J = 8.4, H Ar); 9.29 (2Н, s, H-4,6). 13С NMR
spectrum, δ, ppm: 123.7; 129.9; 130.6; 131.8; 133.0; 139.7;
147.7; 150.7; 157.4. Found, %: C 44.30; H 1.98; Cl 11.50;
N 14.60. C11H6ClN3O5. Calculated, %: C 44.69; H 2.05;
Cl 11.99; N 14.21.
3,5-Dinitro-2-(4-nitrophenoxy)pyridine (8i). Yield
762 mg (83%), white crystals, mp 131–132°С (mp 127°C9).
1Н NMR spectrum, δ, ppm (J, Hz): 7.65 (2H, d, J = 9.0,
H Ar); 8.41 (2H, d, J = 9.0, H Ar); 9.32 (2Н, s, H-4,6).
13С NMR spectrum, δ, ppm: 115.8; 123.1; 125.8; 126.2;
132.0; 140.2; 143.4; 147.7; 156.9. Found, %: C 43.09;
H 1.80; N 18.53. C11H6N4O7. Calculated, %: C 43.15;
H 1.98; N 18.30.
Synthesis of 2-substituted 3,5-dihydropyridines 8j,l
(General method). Appropriate amine (3 mmol) and Et3N
(0.42 ml, 3 mmol) were added to a solution of 2-chloro-
3,5-dinitropyridine (7) (611 mg, 3 mmol) in MeOH (50 ml).
The reaction mixture was stirred at room temperature for
2 h, and complete consumption of the starting materials
was confirmed by TLC (eluent CHCl3). The mixture was
then poured into excess of H2O and acidified with aqueous
HCl to pH 2. The obtained precipitate was filtered off,
washed with H2O (75 ml), and air-dried.
Experimental
1H and 13C NMR spectra were recorded on Bruker AC 200
(200 and 50 MHz, respectively; compounds 10j,m and
11k,n), Bruker AM 300 (300 and 75 MHz, respectively;
compounds 8b,d,h–o, 10b,d,h,i,l,o, and 11j,l), or Bruker
Avance II 600 spectrometers (600 and 150 MHz,
respectively; compound 11m) in DMSO-d6 (compounds
8b,d,h–j,l–o) or CDCl3 (compounds 8k, 10b,d,h–j,l,m,o,
and 11j–n) solutions applying TMS as internal standard.
HRMS analyses were recorded on a Bruker micrOTOF II
mass spectrometer using ESI. Elemental analyses were
performed on a PerkinElmer Series II 2400 instrument.
Melting points were measured on a Stuart SMP20
apparatus. The reaction progress was monitored by TLC
using ALUGRAM SIL G/UV254 plates, which were
visualized by UV light.
All chemicals were purchased from commercial
suppliers and were used directly without purification. Com-
pounds 8a,c,e–g and 10a,c,e–g were synthesized according
to previously described procedures.7
Synthesis of 2-substituted 3,5-dihydropyridines 8b,d
(General method). Appropriate thiol (1 mmol) and Et3N
(0.14 ml, 1 mmol) were added to a solution of 2-chloro-
3,5-dinitropyridine (7) (204 mg, 1 mmol) in MeOH (30 ml).
The reaction mixture was stirred at room temperature for
0.5–2 h until the starting materials were completely
consumed, as indicated by TLC (eluent CHCl3). The
mixture was then poured into H2O and acidified with
aqueous HCl to pH 4. The obtained precipitate was filtered
off, washed with H2O (50 ml), and air-dried.
4-(3,5-Dinitropyridin-2-yl)morpholine (8j). Yield 587 mg
(77%), yellow crystals, mp 146–147°С (mp 85–87°C10).
1Н NMR spectrum, δ, ppm (J, Hz): 3.63–3.67 (8Н, m,
NCH2CH2O); 8.87 (1Н, s, H-6); 9.16 (1Н, s, H-4).
13С NMR spectrum, δ, ppm: 48.1; 65.8; 128.7; 132.3;
133.7; 147.7; 153.0. Found, %: C 42.70; H 3.75; N 22.08.
C9H10N4O5. Calculated, %: C 42.52; H 3.97; N 22.04.
N-Methyl-3,5-dinitro-N-phenylpyridin-2-amine (8l).
Yield 782 mg (95%), beige crystals, mp 141–142°С (mp
2-(Benzylsulfanyl)-3,5-dinitropyridine (8b). Yield
241 mg (83%), yellow crystals, mp 102–103°С. Н NMR
1
1
spectrum, δ, ppm (J, Hz): 4.61 (2H, s, SCH2); 7.26–7.37
(3Н, m, H Ar); 7.50 (2H, d, J = 7.1, H Ar); 9.11 (1H, s,
H-6); 9.61 (1Н, s, H-4). 13С NMR spectrum, δ, ppm: 35.0;
127.4; 128.5; 129.4; 136.1; 140.4; 147.7; 162.4. Found, %:
C 49.36; H 3.25; N 14.30; S 11.32. C12H9N3O4S.
Calculated, %: C 49.48; H 3.11; N 14.43; S 11.01.
135°C11). Н NMR spectrum, δ, ppm (J, Hz): 3.65 (3H, s,
NCH3); 7.21–7.42 (5H, m, H Ar); 8.76 (1Н, s, H-6); 9.31
(1Н, s, H-4). 13С NMR spectrum, δ, ppm: 41.4; 123.5;
127.2; 129.9; 130.3; 131.3; 134.9; 144.6; 147.6; 152.4.
Found, %: C 52.72; H 3.55; N 20.08. C12H10N4O4.
Calculated, %: C 52.56; H 3.68; N 20.43.
Methyl
2-[(3,5-dinitropyridin-2-yl)sulfanyl]acetate
Synthesis of 2-substituted 3,5-dihydropyridines 8k,m,n
(General method). Appropriate amine (6 mmol) was added to a
solution of 2-chloro-3,5-dinitropyridine (7) (611 mg, 3 mmol)
in MeOH (50 ml). The reaction mixture was stirred at room
temperature for 2 h, and complete consumption of starting
material 7 was confirmed by TLC (eluent CHCl3). The
mixture was then poured into excess of H2O and acidified
with aqueous HCl to pH 2. The obtained precipitate was
filtered off, washed with H2O (75 ml), and air-dried.
(8d). Yield 245 mg (90%), brown crystals, mp 115–116°С.
1Н NMR spectrum, δ, ppm (J, Hz): 3.69 (3H, s, OCH3);
4.23 (2H, s, SCH2); 9.13 (1H, d, J = 1.9, H-6); 9.51 (1H, d,
J = 1.9, H-4). 13С NMR spectrum, δ, ppm: 33.4; 52.4;
129.5; 140.5; 140.6; 147.7; 161.7; 168.7. Found, %:
C 35.11; H 2.41; N 15.52; S 11.85. C8H7N3O6S.
Calculated, %: C 35.17; H 2.58; N 15.38; S 11.73.
Synthesis of 2-substituted 3,5-dihydropyridines 8h,i
(General method). Appropriate phenol (3 mmol) and
Na2CO3 (318 mg, 3 mmol) were added to a solution of
N,N-Diethyl-3,5-dinitropyridin-2-amine (8k). Yield
569 mg (79%), orange crystals, mp 60–61°С (mp 59°C11).
75

Chemistry of Heterocyclic Compounds 2019, 55(1), 000–000
1Н NMR spectrum, δ, ppm (J, Hz): 1.30 (6H, t, J = 7.0,
mp 87–88°С. 1Н NMR spectrum, δ, ppm (J, Hz): 2.14 (1H,
t, J = 9.6, 8-CHA); 2.31 (3H, s, NCH3); 2.35 (3H, s, NCH3);
2.53–2.69 (2H, m, 3-CHA, 8-CHB); 2.95 (1H, t, J = 8.5,
1-CHA); 3.05 (1H, d, J = 11.2, 3-CHB); 3.52–3.85 (7H, m,
6-CH2, 1-CHB, OCH3, 8a-CH); 4.19 (2H, d, J = 11.7,
SCH2); 4.93 (1H, d, J = 5.2, 3a-CH). 13С NMR spectrum,
δ, ppm: 32.1; 40.9; 41.5; 44.9; 52.8; 58.9; 61.1; 62.1; 66.4;
92.7; 93.5. Found, m/z: 388.1273 [M+H]+. C14H22N5O6S.
Calculated, m/z: 388.1285.
2NCH2CH3); 3.58 (4H, q, J = 7.1, 2NCH2CH3); 8.83 (1H,
d, J = 2.2, H-6); 9.11 (1H, d, J = 2.2, H-4). 13С NMR
spectrum, δ, ppm: 12.4; 45.2; 129.5; 131.4; 133.5; 147.3;
153.2. Found, %: C 45.11; H 5.25; N 23.08. C9H12N4O4.
Calculated, %: C 45.00; H 5.04; N 23.32.
3,5-Dinitro-2-(pyrrolidin-1-yl)pyridine (8m). Yield
664 mg (93%), yellow crystals, mp 133–134°С (mp 130–
1
132°C12). Н NMR spectrum, δ, ppm: 1.97 (4H, br. s,
2NCH2CH2); 3.34 (4Н, br. s, 2NCH2CH2); 8.86 (1Н, s,
H-6); 9.18 (1Н, s, H-4). 13С NMR spectrum, δ, ppm: 25.7;
50.2; 128.9; 130.9; 132.6; 147.8; 152.7. Found, %:
C 45.11; H 4.55; N 23.78. C9H10N4O4. Calculated, %:
C 45.38; H 4.23; N 23.52.
5-(4-Chlorophenoxy)-2,7-dimethyl-5a,8b-dinitro-
1,2,3,3a,5a,6,7,8,8a,8b-decahydrodipyrrolo[3,4-b:3',4'-d]-
pyridine (10h). Yield 262 mg (64%), beige crystals,
1
mp 134–135°С. Н NMR spectrum, δ, ppm (J, Hz): 2.27–
2.40 (8H, m, 8-CHA, NCH3, 3-CHA); 2.88–3.04 (3H, m,
8-CHB, 1-CHA, 3-CHB); 3.47–3.68 (3H, m, 6-CH2, 1-CHB);
4.06 (1H, d, J = 11.6, 8a-CH); 5.02 (1H, dd, J = 7.4, J = 3.8,
3a-CH); 7.04 (2H, d, J = 8.8, H Ar); 7.35 (2H, d, J = 8.8,
H Ar). 13С NMR spectrum, δ, ppm: 41.2; 46.9; 58.6; 59.0;
63.0; 63.2; 64.8; 89.1; 92.4; 122.9; 129.5; 129.6; 131.2; 150.4;
152.8. Found, m/z: 410.1214 [M+H]+. C17H21ClN5O5.
Calculated, m/z: 410.1226.
3,5-Dinitro-2-(piperidin-1-yl)pyridine (8n). Yield 598 mg
(79%), yellow crystals, mp 154–155°С (mp 147–149°C12).
1Н NMR spectrum, δ, ppm: 1.76 (6H, br. s, NCH2(CH2)3); 3.61
(4Н, br. s, 2NCH2); 8.91 (1Н, s, H-6); 9.09 (1Н, s, H-4).
13С NMR spectrum, δ, ppm: 23.8; 25.8; 49.6; 128.8; 132.0;
133.6; 147.6; 153.8. Found, %: C 47.34; H 4.55; N 22.08.
C10H12N4O4. Calculated, %: C 47.62; H 4.80; N 22.21.
2-Methoxy-3,5-dinitropyridine (8o). A solution of
NaOMe in MeOH (2 M, 1 ml, 2 mmol) was added to a solution
of 2-chloro-3,5-dinitropyridine (7) (407 mg, 2 mmol) in
MeOH (30 ml). The reaction mixture was refluxed for 4 h,
and complete consumption of the starting material 7 was
confirmed by TLC (eluent CHCl3). The mixture was then
poured into excess of H2O and acidified with aqueous HCl
to pH 2. The obtained precipitate was filtered off, washed
with H2O (50 ml), and air-dried. Yield 370 mg (93%),
2,7-Dimethyl-5a,8b-dinitro-5-(4-nitrophenoxy)-
1,2,3,3a,5a,6,7,8,8a,8b-decahydrodipyrrolo[3,4-b:3',4'-d]-
pyridine (10i). Yield 223 mg (53%), white crystals,
1
mp 134–135°С. Н NMR spectrum, δ, ppm (J, Hz): 2.29–
2.42 (8H, m, 8-CHA, NCH3, 3-CHA); 2.98–3.07 (3H, m,
8-CHB, 1-CHA, 3-CHB); 3.44–3.51 (2H, m, 6-CH2); 3.72
(1H, t, J = 8.4, 1-CHB); 4.02 (1H, d, J = 11.3, 8a-CH); 5.06
(1H, dd, J = 7.2, J = 3.8, 3a-CH); 7.30 (2H, d, J = 9.0,
H Ar); 8.30 (2H, d, J = 8.9, H Ar). 13С NMR spectrum,
δ, ppm: 41.7; 47.7; 59.0; 59.9; 62.7; 64.1; 65.2; 89.5; 92.9;
123.0; 126.0; 146.0; 153.1; 157.6. Found, m/z: 421.1450
[M+H]+. C17H21N6O7. Calculated, m/z: 421.1466.
1
brown crystals, mp 70–72°С (mp 88–89°C11). Н NMR
spectrum, δ, ppm: 4.28 (3Н, s, OCH3); 9.01 (1Н, s, H-6);
9.29 (1Н, s, H-4). Found, %: C 36.11; H 2.55; N 21.08.
C6H5N3O5. Calculated, %: C 36.19; H 2.53; N 21.10.
4-(2,7-Dimethyl-5a,8b-dinitro-1,2,3,3a,5a,6,7,8,8a,8b-
decahydrodipyrrolo[3,4-b:3',4'-d]pyridin-5-yl)morpholine
(10j). Yield 44 mg (12%), yellow crystals, mp 131–132°С.
1Н NMR spectrum, δ, ppm (J, Hz): 2.24–2.35 (9H, m,
8-CH2, NCH3, 3-CHA); 2.67 (1H, d, J = 11.7, 3-CHB); 2.85–
2.95 (2H, m, 1-CHA, 6-CHA); 3.04–3.11 (2H, m, 1-CHB,
6-CHB); 3.21–3.28 (2H, m, NCH2CH2O); 3.38–3.48 (2H,
m, NCH2CH2O); 3.61–3.72 (4H, m, 2NCH2CH2O); 4.10
(1H, d, J = 11.6, 8a-CH); 4.95 (1H, s, 3a-CH). 13С NMR
spectrum, δ, ppm: 41.2; 41.6; 46.6; 48.9; 58.3; 58.4; 62.2;
63.8; 65.5; 66.3; 90.2; 92.4; 149.7. Found, m/z: 369.1871
[M+H]+. C15H25N6O5. Calculated, m/z: 369.1881.
N,2,7-Trimethyl-5a,8b-dinitro-N-phenyl-1,2,3,3a,5a,6,
7,8,8a,8b-decahydrodipyrrolo[3,4-b:3',4'-d]pyridin-5-amine
(10l). Yield 16 mg (4%), yellow crystals, mp 180–181°С.
1Н NMR spectrum, δ, ppm (J, Hz): 2.16–2.24 (1H, m,
8-CHA); 2.24 (3H, s, NCH3); 2.27–2.35 (1H, m, 3-CHA);
2.41 (3H, s, NCH3); 2.67 (1H, d, J = 9.7, 8-CHB); 2.85 (1H,
t, J = 8.4, 1-CHA); 3.16 (3H, s, PhNCH3); 3.23–3.26 (1H, m,
6-CHA); 3.50 (1H, d, J = 10.9, 3-CHB); 3.71 (1H, t, J = 8.7,
1-CHB); 4.13 (2H, dd, J = 14.2, J = 7.1, 6-CHB, 8a-CH);
4.98 (1H, d, J = 4.1, 3a-CH); 7.11–7.13 (2H, m, H Ar);
7.29–7.37 (3H, m, H Ar). 13С NMR spectrum, δ, ppm:
29.8; 41.0; 41.9; 42.2; 49.1; 58.1; 58.8; 62.1; 63.9; 66.0;
91.1; 92.7; 128.4; 129.6; 143.4; 149.7. Found, m/z:
389.1937 [M+H]+. C18H25N6O4. Calculated, m/z: 389.1932.
Synthesis of compounds 10b,d,h–j,l,m,o and 11j–n
(General method). A mixture of 2-substituted 3,5-dinitro-
pyridine 8b,d,h–j,l,m,o (1 mmol), paraformaldehyde
(180 mg, 6 mmol), and sarcosine (9) (534 mg, 6 mmol)
was refluxed in PhMe (30 ml) for 0.5–3 h until starting
material 8b,d,h–j,l,m,o was completely consumed, as
indicated by TLC (eluent CHCl3). The mixture was cooled
to room temperature and filtered. The solvent was evapo-
rated under reduced pressure, and the residue was purified
by column chromatography (silica gel, eluent CHCl3).
5-(Benzylsulfanyl)-2,7-dimethyl-5a,8b-dinitro-1,2,3,3a,
5a,6,7,8,8a,8b-decahydrodipyrrolo[3,4-b:3',4'-d]pyridine
(10b). Yield 211 mg (52%), beige crystals, mp 124–125°С.
1Н NMR spectrum, δ, ppm (J, Hz): 2.12 (1H, t, J = 9.5,
8-CHA); 2.29 (6H, s, 2NCH3); 2.43 (1H, d, J = 11.8,
3-CHA); 2.55 (1H, d, J = 9.0, 8-CHB); 2.94 (1H, t, J = 8.4,
1-CHA); 3.05 (1H, d, J = 10.9, 3-CHB); 3.51–3.61 (2Н, m,
6-CH2); 3.74 (1H, t, J = 8.9, 1-CHB); 4.08–4.24 (3Н, m,
8a-CH, SCH2); 4.95 (1H, d, J = 6.0, 3a-CH); 7.30–7.40 (5Н,
m, H Ar). 13С NMR spectrum, δ, ppm: 34.4; 40.8; 41.4;
45.0; 58.9; 60.9; 62.0; 66.1; 127.5; 128.5; 128.9. Found, m/z:
406.1526 [M+H]+. C18H24N5O4S. Calculated, m/z: 406.1544.
Methyl 2-[(2,7-dimethyl-5a,8b-dinitro-1,2,3,3a,5a,6,7,
8,8a,8b-decahydrodipyrrolo[3,4-b:3',4'-d]pyridin-5-yl)-
sulfanyl]acetate (10d). Yield 159 mg (41%), beige crystals,
76

Chemistry of Heterocyclic Compounds 2019, 55(1), 000–000
1
2,7-Dimethyl-5a,8b-dinitro-5-(pyrrolidin-1-yl)-1,2,3,3a,
crystals, mp 98–99°С. Н NMR spectrum, δ, ppm: 1.16–
1.44 (2H, m, N(CH2)2CH2); 1.56–1.77 (4H, m,
2NCH2CH2CH2); 2.61 (3H, s, NCH3); 3.67–3.69 (4H, m,
2NCH2(CH2)2); 4.01 (2H, s, 3-CH2); 4.31 (2H, s, 1-CH2);
8.91 (1H, s, H-6). 13С NMR spectrum, δ, ppm: 25.4; 27.0;
30.4; 42.6; 48.6; 61.8; 62.0; 119.9; 146.0; 149.2; 157.7.
Found, m/z: 263.1504 [M+H]+. C13H19N4O2. Calculated, m/z:
263.1503.
5a,6,7,8,8a,8b-decahydrodipyrrolo[3,4-b:3',4'-d]pyridine
(10m). Yield 46 mg (13%), red crystals, mp 182–183°С.
1Н NMR spectrum, δ, ppm (J, Hz): 1.85–1.90 (4H, m,
2NCH2CH2); 2.25–2.65 (11H, m, 8-CH2, NCH3, 3-CH2,
6-CHA); 2.91 (1H, t, J = 8.4, 1-CHA); 3.05–3.14 (2H, m,
NCH2CH2); 3.28–3.45 (3H, m, 6-CHB, NCH2CH2); 3.64 (1H,
t, J = 9.3, 1-CHB), 4.19 (1H, d, J = 11.7, 8a-CH); 4.94 (1H,
d, J = 4.0, 3a-CH). 13С NMR spectrum, δ, ppm: 25.0; 41.2;
41.7; 47.4; 48.8; 58.1; 58.7; 62.1; 64.7; 65.6; 90.6; 92.8;
147.4. Found, m/z: 353.1936 [M+H]+. C15H25N6O4.
Calculated, m/z: 353.1932.
This work was supported by the Russian Foundation for
Basic Research (grant No. 17-03-00809-a).
References
5-Methoxy-2,7-dimethyl-5a,8b-dinitro-1,2,3,3a,5a,6,7,
8,8a,8b-decahydrodipyrrolo[3,4-b:3',4'-d]pyridine (10o).
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7. Bastrakov, M. A.; Kucherova, A. Yu.; Fedorenko, A. K.;
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1
Yield 97 mg (31%), white crystals, mp 66–68°С. Н NMR
spectrum, δ, ppm (J, Hz): 2.17 (1H, t, J = 9.5, 8-CHA); 2.28
(3H, s, NCH3); 2.30 (3H, s, NCH3); 2.49–2.59 (2H, m,
3-CHA, 8-CHB); 2.90 (1H, t, J = 7.8, 1-CHA); 3.04 (1H, d,
J = 10.8, 3-CHB); 3.46 (1H, d, J = 9.7, 1-CHB); 3.70 (3H, s,
OCH3); 3.93–4.12 (2H, m, 6-CH2); 4.38 (1H, s, 8a-CH); 4.94
(1H, s, 3a-CH). 13С NMR spectrum, δ, ppm: 40.9; 41.4;
42.1; 46.3; 54.1; 54.7; 57.4; 58.4; 58.9; 62.0; 62.7; 63.1;
64.8; 89.6; 93.0; 144.2; 153.1. Found, m/z: 314.1459
[M+H]+. C12H20N5O5. Calculated, m/z: 314.1462.
4-(2-Methyl-7-nitro-2,3-dihydro-1H-pyrrolo[3,4-c]-
pyridin-4-yl)morpholine (11j). Yield 161 mg (61%),
1
orange crystals, mp 178–179°С. Н NMR spectrum, δ, ppm:
2.63 (3H, s, NCH3); 3.70–3.73 (4H, m, 2NCH2CH2O); 3.79–
3.88 (4H, m, 2NCH2CH2O); 4.03 (2H, s, 3-CH2); 4.30 (2H,
s, 1-CH2); 8.93 (1H, s, H-6). 13С NMR spectrum, δ, ppm: 41.9;
47.1; 61.0; 66.9; 120.1; 131.0; 144.9; 149.0; 157.1. Found,
m/z: 265.1300 [M+H]+. C12H17N4O3. Calculated, m/z: 265.1295.
N,N-Diethyl-2-methyl-7-nitro-2,3-dihydro-1H-pyrrolo-
[3,4-c]pyridin-4-amine (11k). Yield 60 mg (24%), red
1
crystals, mp 77–78°С. Н NMR spectrum, δ, ppm: 1.18–
1.24 (6H, m, 2NCH2CH3); 2.69 (3H, s, NCH3); 3.51–3.58
(4H, m, 2NCH2CH3); 4.07 (2H, s, 3-CH2); 4.30 (2H, s, 1-CH2);
8.86 (1H, s, H-6). 13С NMR spectrum, δ, ppm: 14.1; 14.2;
42.0; 43.9; 61.1; 116.9; 132.0; 145.7; 147.7; 156.2. Found,
m/z: 251.1514 [M+H]+. C12H19N4O2. Calculated, m/z: 251.1503.
N,2-Dimethyl-7-nitro-N-phenyl-2,3-dihydro-1H-pyrrolo-
[3,4-c]pyridin-4-amine (11l). Yield 26 mg (9%), red crystals,
1
mp 143–144°С. Н NMR spectrum, δ, ppm (J, Hz): 2.34
(3H, s, NCH3); 2.89 (2H, s, 3-CH2); 3.58 (3H, s, PhNCH3);
4.23 (2H, s, 1-CH2); 7.21 (2H, d, J = 7.6, H Ar); 7.33–7.71
(3H, m, H Ar); 9.06 (1H, s, H-6). 13С NMR spectrum, δ, ppm:
41.1; 41.8; 59.9; 61.3; 121.8; 127.2; 127.4; 129.6; 133.8;
145.2; 145.3; 148.2; 156.4. Found, m/z: 285.1346 [M+H]+.
C15H17N4O2. Calculated, m/z: 285.1346.
2-Methyl-7-nitro-4-(pyrrolidin-1-yl)-2,3-dihydro-1H-
pyrrolo[3,4-c]pyridine (11m). Yield 95 mg (38%), yellow
crystals, mp 212–213°С. 1Н NMR spectrum, δ, ppm: 1.95–
2.05 (4H, m, 2NCH2CH2); 2.58 (3H, s, NCH3); 3.71–3.77
(4H, m, 2NCH2CH2); 4.22 (2H, s, 3-CH2); 4.29 (2H, s, 1-CH2);
8.88 (1H, s, H-6). 13С NMR spectrum, δ, ppm: 25.2; 41.9;
48.4; 60.5; 61.3; 118.1; 132.0; 145.8; 147.3; 155.5. Found, m/z:
249.1349 [M+H]+. C12H17N4O2. Calculated, m/z: 249.1346.
2-Methyl-7-nitro-4-(piperidin-1-yl)-2,3-dihydro-1H-
pyrrolo[3,4-c]pyridine (11n). Yield 71 mg (27%), red
8. Hansch, C.; Leo, A.; Taft, R. W. Chem. Rev. 1991, 91, 165.
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10. Emokpae, T. A.; Uwakwe, P. U.; Hirst, H. J. Chem. Soc.,
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77