Synthesis of 3-R-1,5-dinitro-3-azabicyclo[3.3.1]nonanes fused to azoles

Article abstract of DOI:10.1007/s11172-010-0026-2

3-R-1,5-Dinitro-3-azabicyclo[3.3.1]nonanes fused to the pyrazole, thiazole, and triazole rings were synthesized by reductive cyclization of meta-dinitrobenzazoles.

Full text of DOI:10.1007/s11172-010-0026-2

Russian Chemical Bulletin, International Edition, Vol. 58, No. 2, pp. 421—425, February, 2009
421
Synthesis of 3ꢀRꢀ1,5ꢀdinitroꢀ3ꢀazabicyclo[3.3.1]nonanes
fused to azoles*
E. M. Asadulina, M. A. Bastrakov, A. M. Starosotnikov, V. V. Kachala, and S. A. Shevelev
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5328. Eꢀmail: alexey41@list.ru
3ꢀRꢀ1,5ꢀDinitroꢀ3ꢀazabicyclo[3.3.1]nonanes fused to the pyrazole, thiazole, and triazole
rings were synthesized by reductive cyclization of metaꢀdinitrobenzazoles.
Key words: azabicyclo[3.3.1]nonanes, reduction, Mannich reaction, nitro group, azoles.
The present study is a continuation of our research
on the development of methods for the synthesis of polyꢀ
cyclic fused heterosystems based on fiveꢀmembered
aromatic 4,6ꢀdinitrobenzannulated heterocycles via the
annulation of additional heterocycles using the ability
of the starting dinitrobicyclic compounds to form σH
adducts with nucleophilic reagents.1 The aim of the present
study was to synthesize 3ꢀRꢀ1,5ꢀdinitroꢀ3ꢀazabicyclo[3.3.1]ꢀ
nonanes fused at the C(7)—C(8) bond to different azoles.
Heteroanalogs of bicyclo[3.3.1]nonanes are structural
fragments of terpene alkaloids and have found use as bioꢀ
logically active compounds.2 In recent years, 1,5ꢀdinitroꢀ
3ꢀazabicyclo[3.3.1]nonane derivatives have found to
possess antiarrhythmic activity (see, for example, Ref. 3).
Many of these compounds have been synthesized earꢀ
lier3—6 based on substituted 1,3ꢀdinitrobenzenes (Scheme 1).
The method of synthesis of these compounds involves
the reduction of C=C bonds in the benzene ring activated
by the metaꢀnitro groups with NaBH4 or KBH4 followed
by the double Mannich reaction with formaldehyde and
primary amines.
Scheme 1
i. 1) NaBH4, THF—EtOH—HCONH2; 2) HCHO, R´NH2, AcOH
R = OH, Alk, Hal, OAlk, COOH; R´ = Alk, (CH2)nCOOH
Scheme 2
It should be noted that analogous transformations
of metaꢀdinitrobenzannulated heterocycles are virtually
unknown. Only two syntheses of these compounds conꢀ
taining the pyridine ring were documented.6,7 Data on
the synthesis of 3ꢀazabicyclo[3.3.1]nonanes fused to
fiveꢀmembered heterocycles are lacking in the literature.
We developed a method for the synthesis of 3ꢀRꢀ1,5ꢀ
dinitroꢀ3ꢀazabicyclo[3.3.1]nonanes fused to the pyrazole
ring.8 Isomeric 4,6ꢀdinitroꢀ1ꢀ and 2ꢀphenylindazoles 1
and 2 can be used as the starting compounds for the
synthesis of these compounds. Compounds 1 and 2 can
be prepared based on 2,4,6ꢀtrinitrotoluene (TNT).9,10
or
i. NaBH4, EtOH—THF—HCONH2; ii. CH2O, RNH2, AcOH
5, 6
a
b
c
e
R
Me
5
d
f
R
6
d
f
R
CH(CH3)COOH
(CH2)3COOH
(CH2)3COOH
CH(CH3)COOH
(CH2)2Cl
* On the occasion of the 75th anniversary of the foundation
of the N. D. Zelinsky Institute of Organic Chemistry of the
Russian Academy of Sciences.
CH2COOH
(CH2)2COOH
CHMe2
g
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 413—417, February, 2009.
1066ꢀ5285/09/5802ꢀ0421 © 2009 Springer Science+Business Media, Inc.

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Asadulina et al.
Thus, the reaction of dinitroindazoles 1 and 2 with
the H(2´) and H(6´) protons indicate that the correspondꢀ
ing protons are closely spaced (Fig. 1).
NaBH4 produces hydride adducts 3 and 4,11 whose treatꢀ
ment with a formaldehyde solution and a primary amine
affords tricyclic derivatives, viz., 1,5ꢀdinitroꢀ3ꢀazabicycloꢀ
[3.3.1]nonanes 5 and 6 fused at the C(7)—C(8) bond to
the pyrazole ring (Scheme 2).
The cyclohexene ring is nearly planar. These data
are similar to those obtained for 7ꢀpolyfluoroalkoxyꢀ
1,5ꢀdinitroꢀ3ꢀazabicyclo[3.3.1]nonꢀ6ꢀenes.12,13
In the reaction of 3ꢀcyanoꢀ4,6ꢀdinitroꢀ1ꢀ(4ꢀnitroꢀ
phenyl)indazole 7, which was prepared by the nitration of
the corresponding Nꢀphenyl derivative,14 with NaBH4,
the reduction is selective (only at the dinitrophenyl fragꢀ
ment), and the subsequent double Mannich reaction with
formaldehyde and glycine affords tricyclic derivative 8
in good yield (Scheme 3).
We used alkylamines and amino acids as primary
amines.
The structures of compounds 5 and 6 were confirmed
by NMR and IR spectroscopy and elemental analysis.
The threeꢀdimensional structures of the 1,5ꢀdinitroꢀ
3ꢀazabicyclo[3.3.1]nonane derivatives were determined
based on the study of compound 5а. The complete
assignment of the signals for the hydrogen and carbon
atoms in compound 5а was based on NMR experiments
(1H, 13C, COSY, 2DꢀNOESY, HSQC, and HMBC). The
conformation of the piperidine ring (chair) was estabꢀ
lished based on the NOESY spectrum, in which the corꢀ
relation peaks between the N—CH3 protons and the H(2),
H(2´), H(6), and H(6´) protons and between H(4´) and
Scheme 3
i. NaBH4, EtOH—THF—HCONH2, CH2O, NH2CH2CO2H, AcOH
It was of interest to study the behavior of other readily
available dinitrobenzazoles containing two NO2 groups in
the meta positions in the transformations under considerꢀ
ation. For this purpose, we chose metaꢀdinitro derivatives
of benzothiazole and benzotriazole.
Dinitroꢀsubstituted benzothiazole Nꢀoxide can easily
be synthesized by the treatment of picryl chloride with
methyl thioglycolate in the presence of a small excess of a
base. In this reaction, the intermediate replacement prodꢀ
uct of the chlorine atom 10 undergoes in situ cyclization
via the addition of the active methylene group of the
SCH2CO2Me fragment at the NO2 group.15 The Nꢀoxide
Fig. 1. Structure of compound 5а.
Scheme 4
i. HSCH2CO2Me, Et3N (1 equiv.); ii. Et3N (cat); iii. PCl3, CHCl3, Δ

3ꢀRꢀ1,5ꢀDinitroꢀ3ꢀazabicyclo[3.3.1]nonanes
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 2, February, 2009
423
Scheme 5
i. NaBH4, EtOH—THF—HCONH2; ii. CH2O, RNH2, AcOH
R = CHMe2 (a), Me (b), (CH2)2CO2H (c)
fragment of the thiazole ring in compound 11 is reduced
under reflux in CHCl3 in the presence of PCl3 to form
dinitrobenzothiazole 12 (Scheme 4).
Compound 12, unlike its Nꢀoxide analog 11, reacts
with NaBH4 followed by the double Mannich reaction
under ambient conditions. This reaction produces dinitro
derivatives of 3ꢀazabicyclo[3.3.1]nonane 14 fused to the
thiazole ring in good yields (Scheme 5).
between the hydrogen atoms of the methyl group and all
the three endocyclic nitrogen atoms indicates that the
methyl group in compound 16 is attached at position 2.
We performed the reaction of 2ꢀmethylꢀ4,6ꢀdinitroꢀ
benzotriazole 16 with NaBH4 followed by the double
Mannich reaction under ambient conditions. This reacꢀ
tion produced triazoleꢀcontaining derivative of 1,5ꢀdinitroꢀ
3ꢀazabicyclo[3.3.1]nonane 17.
In the present study, we also examined Nꢀsubstituted
4,6ꢀdinitrobenzotriazole as a heterocyclic compound
because the triazole ring is stable to NaBH4 and it is even
a better electronꢀwithdrawing group compared to pyrazole,
which should facilitate the formation of hydride adducts.
The methylation of 4,6ꢀdinitrobenzotriazole16 15
can theoretically afford three isomeric Nꢀmethyl derivaꢀ
tives. We found and optimize the reaction conditions, in
which one methylation product 16 is predominantly
formed (Scheme 6).
Scheme 7
i. (1) NaBH4, EtOH—THF—HCONH2, (2) CH2O, NH2CH(CH3)2, AcOH
Scheme 6
To sum up, we developed a general method for the
synthesis of 3ꢀRꢀ1,5ꢀdinitroꢀ3ꢀazabicyclo[3.3.1]nonanes
fused with azole (pyrazole, thiazole, and triazole) rings
based on a series of metaꢀdinitroꢀsubstituted benzazoles.
Experimental
1
The H and 13C NMR spectra were recorded on a Bruker
AMꢀ300 instrument. The 14N and 15N NMR spectra were
measured on a Bruker DRXꢀ500 instrument. All experiments
were performed with the use of the Bruker software. The chemiꢀ
cal shifts are given with respect to SiMe4 (1H and 13C) and
CH3NO2 (14N and 15N). The upfield chemical shifts are given
with a minus sign. Samples for NMR spectroscopy were preꢀ
pared in DMSOꢀd6 (unless otherwise stated). The IR spectra
were recorded on a SpecordꢀMꢀ80 instrument in KBr pellets.
The EI mass spectra were obtained on a MSꢀ30 Kratos instruꢀ
ment (70 eV). The course of the reactions was monitored and
the purity of the compounds was checked by TLC on Silufol
UVꢀ254 plates. Dry DMF and MeCN were used. Other solvents
were used without special drying. Compounds 1, 2, 7, 11, 12,
and 15 were synthesized according to procedures described
earlier (see the text).
i. MeI, NaOH, MeCN, 20 °C; ii. MeI, K2CO3, DMF, 20 °C
The structure of the previously unknown compound
16 was determined by 1H, 13C, 14N, and 15N NMR experiꢀ
ments (NOESY, HCQC, HMBC, etc.). The assignment
1
1
was based on the H—13C and H—15N correlations. The
presence of crossꢀpeaks characterizing interactions

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Asadulina et al.
Synthesis of compounds 5, 6, 8, 14, and 17 (general proceꢀ
Calculated (%): C, 55.97; H, 4.99; N, 20.40. 1H NMR, δ:
2.26 (s, 3 H, N—Me); 2.52, 2.60, and 2.72 (all d, 1 H each,
J = 10.1 Hz); 2.92 and 3.05 (both d, 1 H each, J = 11.1 Hz);
3.17 (d, 1 H, J = 8.9 Hz); 3.35—3.54 (m, 2 H); 7.31 (t, 1 H,
dure). Sodium borohydride (0.36 g, 9.5 mmol) was added
portionwise to a solution of the corresponding dinitrobenzazole
(1.7 mmol) in a mixture of THF (2 mL), EtOH (6 mL),
and formamide (4 mL) at a temperature no higher than 10 °C for
20 min. After 30 min, water (7 mL), a mixture of a 30% aqueous
RNH2 solution (2 mL), water (2 mL), a 30% formaldehyde
solution (2 mL), and then glacial AcOH (2 mL) were sucꢀ
cessively added. The reaction mixture was stirred at 20 °C for
30 min and poured into water (150 mL). The precipitate was
filtered off and dried in air.
pꢀHPh); 7.48 (t, 2 H, mꢀHPh, J = 8.1 Hz); 7.85 (d, 2 H, oꢀHPh
,
J = 8.0 Hz); 8.42 (s, 1 H, Pz). IR, ν/cm–1: 1352, 1544 (NO2);
1600 (C=N).
2ꢀ(1,8ꢀDinitroꢀ4ꢀphenylꢀ4,5,10ꢀtriazatricyclo[6.3.1.02,6]ꢀ
dodecaꢀ2,5ꢀdienꢀ10ꢀyl)acetic acid (6b). The yield was 82%,
m.p. 88—90 °C. Found (%): C, 52.63; H, 4.58; N, 17.30.
C17H17N5O6. Calculated (%): C, 52.71; H, 4.42; N, 18.08.
1H NMR, δ: 2.92 (d, 1 H, J = 13.3 Hz); 3.02—3.54 (m,
10ꢀMethylꢀ1,8ꢀdinitroꢀ5ꢀphenylꢀ4,5,10ꢀtriazatriꢀ
cyclo[6.3.1.02,6]dodecaꢀ2(6),3ꢀdiene (5a). The yield was
48%, m.p. 152—154 °C (EtOH). Found (%): C, 56.00; H, 4.80;
N, 20.20. C16H17N5O4. Calculated (%): C, 55.97; H, 4.99;
9 H); 7.28 (t, 1 H, pꢀHPh, J = 8.2 Hz); 7.45 (t, 2 H, mꢀHPh
,
J = 8.2 Hz); 7.80 (d, 2 H, oꢀHPh, J = 8.3 Hz); 8.43 (s, 1 H, Pz).
3ꢀ(1,8ꢀDinitroꢀ4ꢀphenylꢀ4,5,10ꢀtriazatricyclo[6.3.1.02,6]ꢀ
dodecaꢀ2,5ꢀdienꢀ10ꢀyl)propionic acid (6c). The yield was 76%,
m.p. 92—94 °C. Found (%): C, 53.77; H, 4.63. C18H19N5O6.
1
N, 20.40 (C=N). H NMR, δ: 2.34 (s, 3 H, NMe); 2.55 (d,
1 H, J = 10.2 Hz); 2.60 (d, 1 H, J = 10.9 Hz); 2.80 (d, 1 H,
J = 11.8 Hz); 3.09 (d, 1 H, J = 11.8 Hz); 3.27 (d, 1 H, J = 10.2 Hz);
3.31 (d, 1 H, J = 10.9 Hz); 3.41 (d, 1 H, J = 16.6 Hz); 3.47 (d,
1 H, J = 16.7 Hz); 7.43 (m, 1 H, Ph); 7.49—7.51 (m, 4 H, Ph);
7.69 (s, 1 H, Pz). 13C NMR, δ: 33.74, 38.47, 45.03, 62.34, 63.85,
83.80, 85.92, 117.11, 123.46, 128.46, 128.13, 129.51, 135.29,
136.84, 139.11. IR, ν/cm–1: 1352, 1552 (NO2); 1600 (C=N).
2ꢀ(1,8ꢀDinitroꢀ5ꢀphenylꢀ4,5,10ꢀtriazatricyclo[6.3.1.02,6]ꢀ
dodecaꢀ2(6),3ꢀdienꢀ10ꢀyl)acetic acid (5b). The yield was 70%,
m.p. 154—155 °C. Found (%): C, 52.27; H, 4.12; N, 18.08.
C17H17N5O6. Calculated (%): C, 52.71; H, 4.42; N, 17.56.
1H NMR, δ: 2.92 (d, 1 H, J = 12.8 Hz); 3.08 (d, 1 H, J = 12.9 Hz);
3.23—3.57 (m, 7 H); 3.74 (d, 1 H, J = 16.2 Hz); 7.44 (t, 1 H,
pꢀPh, J = 8.1 Hz); 7.52—7.65 (m, 5 H, Pz, Ph).
3ꢀ(1,8ꢀDinitroꢀ5ꢀphenylꢀ4,5,10ꢀtriazatricyclo[6.3.1.02,6]ꢀ
dodecaꢀ2(6),3ꢀdienꢀ10ꢀyl)propionic acid (5c). The yield was 80%,
m.p. 208—210 °C. Found (%): C, 53.86; H, 4.77; N, 17.45.
C18H19N5O6. Calculated (%): C, 54.12; H, 4.57; N, 17.46.
1H NMR, δ: 2.24 (t, 2 H, CH2, J = 5.1 Hz); 2.60—3.53 (m, 9
H); 3.72 (d, 1 H, J = 16.2 Hz); 7.41—7.64 (m, 6 H, Pz, Ph).
2ꢀ(1,8ꢀDinitroꢀ5ꢀphenylꢀ4,5,10ꢀtriazatricyclo[6.3.1.02,6]ꢀ
dodecaꢀ2(6),3ꢀdienꢀ10ꢀyl)propionic acid (5d). The yield was 68%,
m.p. 193—194 °C. Found (%): C, 53.83; H, 4.97; N, 16.65.
C18H19N5O6. Calculated (%): C, 53.86; H, 4.77; N, 17.45.
1H NMR, δ: 0.89 and 1.04 (both d, 3 H, CH3 (mixture of
diastereomers), J = 7.6 Hz); 2.92—3.53 (m, 8 H); 3.73 (d, 1 H,
J = 16.1 Hz); 7.43—7.62 (m, 6 H, Pz, Ph).
1
Calculated (%): C, 53.86; H, 4.77. H NMR, δ: 2.25 (t, 2 H,
CH2, J = 6.6 Hz); 2.65—3.62 (m, 10 H); 7.28 (t, 1 H, pꢀHPh
,
J = 8.0 Hz); 7.46 (t, 2 H, mꢀHPh, J = 8.1 Hz); 7.82 (d, 2 H,
oꢀHPh, J = 8.1 Hz); 8.38 (s, 1 H, Pz).
4ꢀ(1,8ꢀDinitroꢀ4ꢀphenylꢀ4,5,10ꢀtriazatricyclo[6.3.1.02,6]ꢀ
dodecaꢀ2,5ꢀdienꢀ10ꢀyl)butyric acid (6d). The yield was 75%,
m.p. 75 °C. Found (%): C, 55.11; H, 5.36. C19H21N5O6. Calcuꢀ
1
lated (%): C, 54.94; H, 5.10. H NMR, δ: 1.48 (m, 2 H, CH2);
1.86 (m, 2 H, CH2); 2.48 (m, 2 H, CH2); 2.73—3.30 (m, 5 H);
3.34—3.62 (m, 3 H); 7.29 (t, 1 H, pꢀHPh, J = 8.5 Hz); 7.48 (t,
2 H, mꢀHPh, J = 8.4 Hz); 7.80 (d, 2 H, oꢀHPh, J = 8.6 Hz); 8.35
(s, 1 H, Pz).
10ꢀIsopropylꢀ1,8ꢀdinitroꢀ4ꢀphenylꢀ4,5,10ꢀtriazatriꢀ
cyclo[6.3.1.02,6]dodecaꢀ2,5ꢀdiene (6e). The yield was 83%,
m.p. 139—141 °C. Found (%): C, 58.24; H, 5.92; N, 18.28.
C18H21N5O4. Calculated (%): C, 58.21; H, 5.70; N, 18.86.
1H NMR, δ: 0.81 (d, 3 H, CH3, J = 8.6 Hz); 0.90 (d, 3 H,
CH3, J = 8.6 Hz); 2.80—3.52 (m, 9 H); 7.28 (t, 1 H, pꢀHPh
,
J = 8.1 Hz); 7.47 (t, 2 H, mꢀHPh, J = 8.1 Hz); 7.83 (d, 2 H,
oꢀHPh, J = 8.0 Hz); 8.37 (s, 1 H, Pz).
2ꢀ(1,8ꢀDinitroꢀ4ꢀphenylꢀ4,5,10ꢀtriazatricyclo[6.3.1.02,6]ꢀ
dodecaꢀ2,5ꢀdienꢀ10ꢀyl)propionic acid (6f). The yield was 76%,
m.p. 188—190 °C. Found (%): C, 53.60; H, 5.10; N, 16.80.
C18H19N5O6. Calculated (%): C, 53.86; H, 4.77; N, 17.45.
1H NMR, δ: 0.88 and 1.08 (both d, 3 H, CH3 (for a mixture
of diastereomers), J = 8.6 Hz); 2.95—3.58 (m, 9 H); 7.29 (t,
1 H, pꢀHPh, J = 8.5 Hz); 7.47 (t, 2 H, mꢀHPh, J = 8.6 Hz); 7.83
(d, 2 H, oꢀHPh, J = 8.6 Hz); 8.41 (s, 1 H, Pz).
10ꢀIsopropylꢀ1,8ꢀdinitroꢀ5ꢀphenylꢀ4,5,10ꢀtriazatricycloꢀ
[6.3.1.02,6]dodecaꢀ2(6),3ꢀdiene (5e). The yield was 72%,
m.p. 96—98 °C. Found (%): C, 58.00; H, 5.80; N, 18.60.
C18H21N5O4. Calculated (%): C, 58.21; H, 5.70; N, 18.86.
1H NMR, δ: 0.88 (d, 3 H, CH3, J = 8.6 Hz); 1.06 (d, 3 H, CH3,
J = 8.6 Hz); 2.91—3.67 (m, 9 H); 7.38—7.63 (m, 6 H, Pz, Ph).
4ꢀ(1,8ꢀDinitroꢀ5ꢀphenylꢀ4,5,10ꢀtriazatricyclo[6.3.1.02,6]ꢀ
dodecaꢀ2(6),3ꢀdienꢀ10ꢀyl)butyric acid (5f). The yield was
75%, m.p. 79—81 °C. Found (%): C, 54.82; H, 5.30; N, 16.57.
C19H21N5O6. Calculated (%): C, 54.94; H, 5.10; N, 16.86.
1H NMR, δ: 1.46 (m, 2 H, CH2); 1.78 (m, 2 H, CH2); 2.41 (m,
2 H, CH2); 2.68 (d, 1 H, J = 10.7 Hz); 2.75 (d, 1 H, J = 10.7 Hz);
2.94 (d, 1 H, J = 10.7 Hz); 3.10 (t, 2 H, J = 12.9 Hz); 3.32 (d,
2 H, J = 17.5 Hz); 3.79 (d, 1 H, J = 17.5 Hz); 7.42—7.63 (m,
6 H, Pz, Ph).
10ꢀ(2ꢀChloroethyl)ꢀ1,8ꢀdinitroꢀ4ꢀphenylꢀ4,5,10ꢀtriazaꢀ
tricyclo[6.3.1.02,6]dodecaꢀ2,5ꢀdiene (6g). The yield was 16%,
m.p. 65—67 °C. Found (%): C, 52.13; H, 4.73; Cl, 9.35.
C17H18ClN5O4. Calculated (%): C, 52.11; H, 4.63; Cl, 9.05.
1H NMR, δ: 2.71—3.10 (m, 6 H); 3.23—3.58 (m, 6 H); 7.30 (t,
1 H, pꢀHPh, J = 8.1 Hz); 7.47 (t, 2 H, mꢀHPh, J = 8.1 Hz); 7.82
(d, 2 H, oꢀHPh, J = 8.2 Hz); 8.42 (s, 1 H, Pz).
2ꢀ[3ꢀCyanoꢀ1,8ꢀdinitroꢀ5ꢀ(4ꢀnitrophenyl)ꢀ4,5,10ꢀtriazaꢀ
tricyclo[6.3.1.02,6]dodecaꢀ2(6),3ꢀdienꢀ10ꢀyl]acetic acid (8). The
yield was 75%, m.p. 178—180 °C. Found (%): C, 47.34; H, 3.03.
C18H15N7O8. Calculated (%): C, 47.27; H, 3.31. 1H NMR,
δ: 2.95—3.45 (m, 8 H); 3.60 (d, 1 H, J = 18.6 Hz); 3.93 (d, 1 H,
J = 18.6 Hz); 8.00 (d, 2 H, 4ꢀNO2C6H4, J = 9.4 Hz); 8.43 (d,
2 H, 4ꢀNO2C6H4, J = 9.4 Hz).
10ꢀMethylꢀ1,8ꢀdinitroꢀ4ꢀphenylꢀ4,5,10ꢀtriazatricyclo[6.3.1.02,6]ꢀ
dodecaꢀ2,5ꢀdiene (6a). The yield was 29%, m.p. 127—129 °C
(EtOH). Found (%): C, 56.45; H, 4.91; N, 20.00. C16H17N5O4.
Methyl 10ꢀisopropylꢀ1,8ꢀdinitroꢀ3ꢀthiaꢀ5,10ꢀdiazatricycloꢀ
[6.3.1.02,6]dodecaꢀ2(6),4ꢀdieneꢀ4ꢀcarboxylate (14a). The yield

3ꢀRꢀ1,5ꢀDinitroꢀ3ꢀazabicyclo[3.3.1]nonanes
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 2, February, 2009
425
was 0.25 g (40%), m.p. 147—150 °C. Found (%): C, 45.76;
H, 5.13; N, 15.04. C14H18N4O6S. Calculated (%): C, 45.40;
H, 4.90; N, 15.13. 1H NMR, δ: 0.72 (d, 3 H, CH3, J = 6.5 Hz);
0.83 (d, 3 H, CH3, J = 6.4 Hz); 2.80 (m, 1 H); 2.95 (m, 2 H);
3.12 (m, 2 H); 3.35 (m, 2 H); 3.47 (d, 1 H, J = 16.7 Hz); 3.59
(d, 1 H, J = 16.7 Hz); 3.91 (s, 3 H, Me).
[Russ. Chem. Bull., Int. Ed., 2008, No. 7]; (b) M. A.
Bastrakov, A. M. Starosotnikov, V. V. Kachala, I. V. Glukhov,
S. A. Shevelev, Izv. Akad. Nauk, Ser. Khim., 2009, 407 [Russ.
Chem. Bull., Int. Ed., 2009, 58, No. 2].
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[Russ. Chem. Rev. (Engl. Transl.), 1973, 42, 190].
3. N. N. Yarmukhamedov, L. T. Karachurina, R. Yu.
Khisamutdinova, F. S. Zarudnii, N. Z. Baibulatova,
F. N. Dzhakhangirov, V. A. Dokichev, Yu. V. Tomilov,
M. S. Yunusov, O. M. Nefedov, RF Pat. 2228334, July 22,
2002, Byul. Izobr., 2004, No. 13 (in Russian).
Methyl 10ꢀmethylꢀ1,8ꢀdinitroꢀ3ꢀthiaꢀ5,10ꢀdiazatricycloꢀ
[6.3.1.02,6]dodecaꢀ2(6),4ꢀdieneꢀ4ꢀcarboxylate (14b). The yield
was 0.3 g (52%), m.p. 164—168 °C. Found (%): C, 42.21;
H, 4.23; N, 16.15. C12H14N4O6S. Calculated (%): C, 42.10;
1
H, 4.12; N, 16.37. H NMR, δ: 2.22 (s, 3 H); 2.68 (d, 1 H,
J = 10.5 Hz); 2.75 (d, 1 H, J = 10.5 Hz); 3.17 (m, 3 H); 3.35 (m,
1 H); 3.53 (d, 1 H, J = 16.8 Hz); 3.62 (d, 1 H, J = 16.8 Hz); 3.91
(s, 3 H, Me).
3ꢀ[4ꢀ(Methoxycarbonyl)ꢀ1,8ꢀdinitroꢀ3ꢀthiaꢀ5,10ꢀdiazatriꢀ
cyclo[6.3.1.02,6]dodecaꢀ2(6),4ꢀdienꢀ10ꢀyl]propionic acid (14c).
The yield was 0.14 g (41%), m.p. 202—206 °C. Found (%):
C, 42.14; H, 4.07; N, 13.77. C14H16N4O8S. Calculated (%):
C, 42.00; H, 4.03; N, 13.99. 1H NMR, δ: 2.19 (m, 2 H); 2.64—3.72
(m, 10 H); 3.91 (s, 3 H, Me); 12.00 (br.s, 1 H).
4. T. Severin, R. Schmitz, M. Adam, Chem. Ber., 1963, 96,
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2001, 41, 1238].
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Starosotnikov, S. A. Shevelev, Mendeleev Commun.,
2008, 213.
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Shevelev, Izv. Akad. Nauk, Ser. Khim., 2004, 557 [Russ.
Chem. Bull., Int. Ed., 2004, 53, 584].
10. (a) A. M. Kuvshinov, V. I. Gulevskaya, V. V. Rozhkov, S. A.
Shevelev, Synthesis, 2000, 10, 1474; (b) D. A. Brovko,
V. N. Marshalkin, V. V. Semenov, Khim. Geterotsikl. Soedin.,
2001, 37, 552 [Chem. Heterocycl. Compd. (Engl. Transl.),
2001, 37, 504].
11. E. Buncel, M. R. Crampton, M. J. Strauss, F. Terrier,
Electron Deficient Aromaticꢀ and HeteroaromaticꢀBase Interꢀ
actions, Elsevier, Amsterdam, 1984, p. 422.
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M. D. Dutov, Yu. D. Grudtsin, Yu. M. Atroshchenko,
S. A. Shevelev, V. A. Subbotin, Zh. Org. Khim., 2001, 37, 771
[Russ. J. Org. Chem. (Engl. Transl.), 2001, 37, 734].
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Shakhkeldyan, E. N. Alifanova, Acta Cryst., 1998, C54, 271.
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Vinogradov, S. A. Shevelev, Izv. Akad. Nauk, Ser. Khim.,
2003, 1690 [Russ. Chem. Bull., Int. Ed., 2003, 52, 1782].
15. (a) K. Bertolasi, K. Dudova, P. Simunek, J. Cerny,
V. Machacek, J. Mol. Struct., 2003, 658, 33; (b) K. Wagner,
H. Heitzer, L. Oehlmann, Chem. Ber., 1973, 106, 640;
(c) M. Janik, V. Machacek, O. Pytela, Collect. Czech. Chem.
Commun., 1997, 62, 1429.
10ꢀIsopropylꢀ4ꢀmethylꢀ1,8ꢀdinitroꢀ3,4,5,10ꢀtetraazaꢀ
tricyclo[6.3.1.02,6]dodecaꢀ2,5ꢀdiene (17). The yield was 0.32 g
(57%), m.p. 125—128 °C. Found (%): C, 46.41; H, 5.86;
N, 27.15. C12H18N6O4. Calculated (%): C, 46.45; H, 5.85;
N, 27.08. 1H NMR, δ: 0.78 (d, 3 H, CH3, J = 6.4 Hz); 0.86 (d,
3 H, CH3, J = 6.4 Hz); 2.81 (d, 2 H, J = 10.5 Hz); 2.98 (d,
2 H, J = 10.2 Hz); 3.16 (m, 2 H); 3.35 (m, 2 H); 3.53 (d, 1 H,
J = 10.2 Hz); 4.08 (s, 3 H, N—Me).
2ꢀMethylꢀ4,6ꢀdinitroꢀ2Hꢀ1,2,3ꢀbenzotriazole (16). Sodium
hydroxide (0.43 g, 0.0107 mol) was added to a solution of
dinitrobenzotriazole 15 (2.25 g, 0.0107 mol) in dry acetonitrile
(40 mL). The reaction mixture was cooled to 0 °C, and CH3I
(0.67 mL, 0.0108 mol) was added. Then the reaction mixture
was kept at 0 °C for 3 h, CH3I (1.34 mL, 0.0216 mol) was added,
and the mixture was allowed to stand at room temperature for
3 days, poured into water (150 mL), and extracted with ethyl
acetate (3×50 mL). The organic layer was washed with water,
dried over Na2SO4, and concentrated to dryness. The residue was
washed with hot ethanol and recrystallized from chloroform.
The yield of compound 16 was 0.671 g (28%), m.p. 206—208 °C
(CHCl3). Found (%): C, 37.43; H, 2.54; N, 31.73. C7H5N5O4.
Calculated (%): C, 37.68; H, 2.26; N, 31.38. 1H NMR (CDCl3),
δ: 4.78 (s, 3 H, Me); 9.24 (s, 1 H, H(5)); 9.25 (s, 1 H, H(7)).
13C NMR (CDCl3), δ: 45.0, 119.0, 122.5, 137.8, 139.3, 144.8,
145.4. 14N NMR (CDCl3), δ: –26.5 (NO2). 15N NMR (CDCl3),
δ: –100.9 (N(2)); –59.7 (N(1)); –50.4 (N(3)).
This study was financially supported by the Russian
Foundation for Basic Research (Project No. 07ꢀ03ꢀ00414)
and the Council on Grants at the President of the Russian
Federation (Program for State Support of Young Scientists
of the Russian Federation, Grant MKꢀ1293.2008.3).
16. C. J. McHugh, D. R. Tackley, D. Graham, Heterocycles,
2002, 57, 1461.
References
1. (а) M. A. Bastrakov, A. M. Starosotnikov, A. Kh. Shakhnes,
S. A. Shevelev, Izv. Akad. Nauk, Ser. Khim., 2008, 1508
Received July 2, 2008