Synthesis of pyrazole- and thiazole-annulated 3-R-1,5-dinitro-3- azabicyclo[3.3.1]nonanes

Article abstract of DOI:10.1007/s11172-012-0086-6

The previously unknown 3-R-1,5-dinitro-3-azabicyclo[3.3.1]nonanes fused to the pyrazole or thiazole rings were synthesized by the reductive cyclization of m-dinitroindazoles and benzothiazoles. The method is based on the reduction of carbon-carbon bonds i

Full text of DOI:10.1007/s11172-012-0086-6

Russian Chemical Bulletin, International Edition, Vol. 61, No. 3, pp. 596—599, March, 2012
596
Synthesis of pyrazoleꢀ and thiazoleꢀannulated
3ꢀRꢀ1,5ꢀdinitroꢀ3ꢀazabicyclo[3.3.1]nonanes
A. V. Puchnin,a M. A. Bastrakov,b A. M. Starosotnikov,b S. V. Popkov,a and S. A. Shevelevb
aD. I. Mendeleev University of Chemical Technology of Russia,
9 pl. Miusskaya, 125047 Moscow, Russian Federation
bN. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5328. Eꢀmail: shevelev@ioc.ac.ru
The previously unknown 3ꢀRꢀ1,5ꢀdinitroꢀ3ꢀazabicyclo[3.3.1]nonanes fused to the pyrꢀ
azole or thiazole rings were synthesized by the reductive cyclization of mꢀdinitroindazoles and
benzothiazoles. The method is based on the reduction of carbon—carbon bonds in the benzene
ring, which are activated by the metaꢀnitro groups, with NaBH4 followed by the Mannich
reaction with formaldehyde and primary amines.
Key words: azabicyclo[3.3.1]nonanes, reduction, Mannich reaction, nitro group, azoles.
Scheme 1
The present study is a continuation of our works to
develop methods for the synthesis of polycyclic fused hetꢀ
erosystems based on fiveꢀmembered aromatic 4,6ꢀdiꢀ
nitrobenzannulated heterocycles employing the ability of
the starting dinitro compounds to form Hꢀadducts with
nucleophilic reagents.1 The purpose of the present work
was to synthesize new 3ꢀRꢀ1,5ꢀdinitroꢀ3ꢀazabicycloꢀ
[3.3.1]nonanes fused to substituted pyrazoles and thiazoles
at the C(7)—C(8) bond.
R = OH, Alk, Hal, OAlk, COOH
R´ = Alk, (CH2)nCOOH
Heteroanalogs of bicyclo[3.3.1]nonanes are structural
fragments of terpenoid alkaloids and are used as biologiꢀ
cally active compounds.2 1,5ꢀDinitroꢀ3ꢀazabicyclo[3.3.1]ꢀ
nonane derivatives were found to have high antiarrhythꢀ
mic activity (see, for example, Ref. 3). Many of these
compounds have been synthesized previously3—6 based on
substituted 1,3ꢀdinitrobenzenes (Scheme 1). The method for
their synthesis involves the reduction of carbon—carbon
bonds in the benzene ring, which are activated by the metaꢀ
nitro groups, with NaBH4 or KBH4 followed by the double
Mannich reaction with formaldehyde and primary amines.
However, similar transformations of mꢀdinitrobenzanꢀ
nulated heterocycles are poorly known. Thus, except
for our studies (see below), a few examples of the synthesis
of such compounds containing the pyridine ring were reꢀ
ported.6,7
i. 1) NaBH4, THF—EtOH—HCONH2; 2) HCHO, R´NH2,
AcOH.
bility, certain useful physiological activities (psychotropic,
antihypoxic, antineurotoxic, and so on). It would be exꢀ
pected that compounds containing the C2—C3 alkyl or
ꢀmethoxyalkyl substituent at the nitrogen atom of the
piperidine ring will exhibit the highest activity. Previousꢀ
ly,9 we have shown that such derivatives containing the
Nꢀcarboxyalkyl group can be, in principle, synthesized.
Hence, we continued studies aimed at preparing 3ꢀazaꢀ
bicyclo[3.3.1]nonanes fused to the pyrazole ring. These
compounds can be synthesized starting from isomeric
4,6ꢀdinitroꢀ1ꢀ and ꢀ2ꢀphenylindazoles 1 and 2, which can
be prepared based on trinitrotoluene (TNT).10,11
Thus, the reactions of compounds 1 and 2 with NaBH4
afford reduction products 3 and 4,12 whose treatment with
a formaldehyde solution and primary amines gives triꢀ
cyclic derivatives, viz., 1,5ꢀdinitroꢀ3ꢀazabicyclo[3.3.1]ꢀ
nonanes 5 or 6 annulated to the pyrazole ring at the
C(7)—C(8) bond (Scheme 2).
According to preliminary calculations for biological
activity with the use of the PASS program (see Ref. 8),*
some 1,5ꢀdinitroꢀ3ꢀazabicyclo[3.3.1]nonanes containing
the pyrazole or thiazole moiety can have, with high probaꢀ
Then, we performed the reaction under consideration
with the use of 4,6ꢀdinitrobenzothiazoles containing the
* The results of the testing of some compounds synthesized in
the present study will be published elsewhere.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 594—597, March, 2012.
1066ꢀ5285/12/6103ꢀ596 © 2012 Springer Science+Business Media, Inc.

1,5ꢀDinitroꢀ3ꢀazabicyclo[3.3.1]nonanes
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 3, March, 2012
597
Scheme 2
5: R = CH2CH2OH (a), CH2CH2OMe (b), Et (c), Pr (d), (CH2)3OMe (e)
6: R = CH2CH2OMe
i. NaBH4, EtOH—THF—HCONH2; ii. CH2O, RNH2, AcOH.
Scheme 3
acetylamino or propionylamino substituent at position 2
as the starting compounds. These compounds were synꢀ
thesized by the nitration of 2ꢀaminobenzothiazole 7 with
nitric acid in oleum13 followed by the acylation of dinitro
derivative 8 with acetic or propionic anhydride (Scheme 3).
Dinitrobenzothiazoles 9 and 10 are easily reduced with
NaBH4 followed by the Mannich reaction, as was observed
for compounds 1 and 2; in these reactions, a THF—EtOH
mixture was used as the solvent. As a result, we syntheꢀ
sized a series of the previously unknown 3ꢀazabicycloꢀ
[3.3.1]nonanes fused to the thiazole ring in good yields
(Scheme 4).
The structures of all synthesized compounds were conꢀ
1
firmed by H NMR and IR spectroscopy, as well as by
elemental analysis.
To summarize, we synthesized a series of new 3ꢀsubꢀ
stituted 1,5ꢀdinitroꢀ3ꢀazabicyclo[3.3.1]nonanes fused to
R = Me (9), Et (10)
i. HNO3, oleum, 20 C; ii. (RCO)2O, .
Scheme 4
Compound
9
10
11
R´
Compound
12
13a
R
COEt
CH2COOH
(CH2)3OMe
Compound
13c
13d
R
Et
Compound
14b
14c
R
COMe
COEt
COMe
(CH2)3OMe
CH2COOH
(CH2)2OMe
(CH2)2OMe
Me
13b
14a
14d
i. NaBH4, EtOH—THF; ii. CH2O, RNH2, AcOH.

598
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 3, March, 2012
Puchnin et al.
6ꢀ(2ꢀMethoxyethyl)ꢀ4,8ꢀdinitroꢀ2ꢀphenylꢀ4,5,6,7,8,9ꢀhexaꢀ
hydroꢀ2Hꢀ4,8ꢀmethanopyrazolo[4,3ꢀd]azocine (6). The yield was
78%, m.p. 109—111 C. Found (%): C, 55.75; H, 5.15; N, 18.18.
C18H21N5O5. Calculated (%): C, 55.81; H, 5.46; N, 18.08.
1H NMR, : 2.50—2.73 (m, 9 H); 2.84—3.52 (m, 6 H); 7.29
(t, 1 H, pꢀPh, J = 7.3 Hz); 7.47 (t, 2 H, mꢀPh, J = 7.8 Hz); 7.83
the pyrazole or thiazole ring starting from dinitro derivaꢀ
tives of indazoles and benzothiazoles.
Experimental
(d, 2 H, mꢀPh, J = 8.0 Hz); 8.41 (s, 1 H, pyrazole). IR, /cm–1
:
The 1H NMR spectra were recorded on a Bruker AМꢀ300
instrument in DMSOꢀd6; the chemical shifts are given with reꢀ
spect to Me4Si. The IR spectra were measured on a Bruker Alpha
instrument (KBr pellets). The course of the reactions was moniꢀ
tored and the purity of the compounds was checked by TLC on
Silufol UVꢀ254 plates. Compounds 1,10 2,11 and 8 (see Ref. 13)
were synthesized according to procedures described previously.
Synthesis of compounds 5 and 6 (general procedure). Sodium
borohydride (0.43 g, 11.4 mmol) was added portionwise to
a solution of compound 1 or 2 (0.57 g, 2 mmol) in a mixture of
THF (3 mL), EtOH (8 mL), and formamide (6 mL) at a temperꢀ
ature 10 C for 20 min. After 30 min, water (10 mL), a mixture
of a 30% aqueous solution of RNH2 (2.5 mL) and a 30% formalꢀ
dehyde solution (2.5 mL), and then glacial AcOH (2.5 mL) were
successively added. The reaction mixture was stirred at 20 C for
30 min and then poured into water (200 mL). The precipitate
that formed was filtered off and dried in air.
2ꢀ(4,8ꢀDinitroꢀ1ꢀphenylꢀ1,4,5,7,8,9ꢀhexahydroꢀ6Hꢀ4,8ꢀ
methanopyrazolo[4,3ꢀd]azocinꢀ6ꢀyl)ethanol (5a). The yield was
23%, m.p. 103—105 C. Found (%): C, 54.43; H, 5.27; N, 18.32.
C17H19N5O5. Calculated (%): C, 54.69; H, 5.13; N, 18.76.
1H NMR, : 2.44—3.78 (m, 13 H); 7.42—7.61 (m, 6 H, Ph,
pyrazole). IR, /cm–1: 694, 763, 968, 1066, 1366, 1413, 1455,
1506, 1546, 1598, 1664, 3406.
6ꢀ(2ꢀMethoxyethyl)ꢀ4,8ꢀdinitroꢀ1ꢀphenylꢀ4,5,6,7,8,9ꢀhexaꢀ
hydroꢀ1Hꢀ4,8ꢀmethanopyrazolo[4,3ꢀd]azocine (5b). The yield
was 81%, m.p. 127—129 C. Found (%): C, 55.96; H, 5.31; N, 17.92.
C18H21N5O5. Calculated (%): C, 55.81; H, 5.46; N, 18.08.
1H NMR, : 2.50—3.41 (m, 14 H); 3.79 (d, 1 H, J = 16.3 Hz);
7.42—7.61 (m, 6 H, pyrazole, Ph).
6ꢀEthylꢀ4,8ꢀdinitroꢀ1ꢀphenylꢀ4,5,6,7,8,9ꢀhexahydroꢀ1Hꢀ
4,8ꢀmethanopyrazolo[4,3ꢀd]azocine (5c). The yield was 49%,
m.p. 115—116 C. Found (%): C, 56.98; H, 5.23; N, 19.43.
C17H19N5O4. Calculated (%): C, 57.14; H, 5.36; N, 19.60.
1H NMR, : 0.84 (t, 3 H, Me, J = 7.1 Hz); 2.43—2.59 (m, 3 H);
2.65 (d, 1 H, J = 10.4 Hz); 2.80 (d, 1 H, J = 10.1 Hz); 2.93
(d, 1 H, J = 11.2 Hz); 3.06 (d, 1 H, J = 11.2 Hz); 3.17 (d, 1 H,
J = 10 Hz); 3.40 (d, 1 H, J = 16.2 Hz); 3.80 (d, 1 H, J = 16.4 Hz);
7.42—7.62 (m, 6 H, Ph, pyrazole).
4,8ꢀDinitroꢀ1ꢀphenylꢀ6ꢀpropylꢀ4,5,6,7,8,9ꢀhexahydroꢀ1Hꢀ
4,8ꢀmethanopyrazolo[4,3ꢀd]azocine (5d). The yield was 11%,
m.p. 103—104 C. Found (%): C, 58.36; H, 5.58; N, 18.93.
C18H21N5O4. Calculated (%): C, 58.21; H, 5.70; N, 18.86.
1H NMR, : 0.50 (t, 3 H, J = 7.2 Hz); 1.21—1.30 (m, 2 H); 2.37
(d, 2 H, J = 2.1 Hz); 2.52 (d, 1 H, J = 11.4 Hz); 2.67 (d, 1 H,
J = 10.5 Hz); 2.76 (d, 1 H, J = 10.0 Hz); 2.94 (d, 1 H, J = 11.1 Hz);
3.11 (m, 2 H); 3.33 (d, 1 H, J = 15.3 Hz); 3.80 (d, 1 H, J = 16.3 Hz);
7.43—7.62 (m, 6 H, Ph, pyrazole).
6ꢀ(3ꢀMethoxypropyl)ꢀ4,8ꢀdinitroꢀ1ꢀphenylꢀ4,5,6,7,8,9ꢀhexaꢀ
hydroꢀ1Hꢀ4,8ꢀmethanopyrazolo[4,3ꢀd]azocine (5e). The yield
was 30%, m.p. 134—135 C. Found (%): C, 57.01; H, 5.82;
N, 17.37. C19H23N5O5. Calculated (%): C, 56.85; H, 5.78;
N, 17.45. 1H NMR, : 1.41—1.49 (m, 2 H); 2.43—3.34
(m, 14 H); 3.82 (d, 1 H, J = 16.4 Hz); 7.42—7.63 (m, 6 H, Ph,
pyrazole).
691, 757, 812, 1012, 1114, 1209, 1460, 1504, 1541, 1598.
Synthesis of compounds 9 and 10 (general procedure). A soluꢀ
tion of the starting benzothiazole 8 (6 mmol) in acetic (propꢀ
ionic) anhydride (30 mL) was kept at 50—70 C for 2 h. Then the
reaction mixture was concentrated, EtOH (25 mL) was added
to the residue, and the mixture was again concentrated. The
precipitate that formed was washed with H2O, filtered off, and
dried in air.
Nꢀ(4,6ꢀDinitroꢀ1,3ꢀbenzothiazolꢀ2ꢀyl)acetamide (9). The
yield was 93%, m.p. >260 C. 1H NMR, : 2.29 (s, 3 H); 8.89
(s, 1 H); 9.40 (s, 1 H); 13.32 (s, 1 H).
Nꢀ(4,6ꢀDinitroꢀ1,3ꢀbenzothiazolꢀ2ꢀyl)propanamide (10). The
yield was 91%, m.p. >260 C. 1H NMR, : 1.13 (t, 3 H,
J = 7.4 Hz); 2.61 (q, 2 H, J = 7.5 Hz); 8.88 (s, 1 H); 9.40 (s, 1 H);
13.28 (s, 1 H).
Synthesis of compounds 13 and 14 (general procedure). Sodium
borohydride (0.23 g, 6 mmol) was added portionwise to a soluꢀ
tion of benzothiazole 9 or 10 (1 mmol) in a mixture of THF
(4 mL) and EtOH (12 mL) at a temperature 10 C for 15 min.
After 1 h, water (9 mL), a mixture of a 30% aqueous solution of
RNH2 (2.5 mL), water (2.5 mL), and a 30% formaldehyde soluꢀ
tion, and then glacial AcOH (2.5 mL) were successively added.
The reaction mixture was stirred at 20 C for 30 min and then
poured into water (200 mL). The precipitate was filtered off and
dried in air.
[2ꢀ(Acetylamino)ꢀ4,8ꢀdinitroꢀ4,7,8,9ꢀhexahydroꢀ4,8ꢀmethꢀ
ano[1,3]thiazolo[4,5ꢀd]azocinꢀ6(5H)ꢀyl]acetic acid (13a). The
yield was 63%, m.p. 281 C. Found (%): C, 40.43; H, 3.97;
N, 18.37. C13H15N5O7S. Calculated (%): C, 40.52; H, 3.92;
N, 18.17. 1H NMR, : 2.09 (s, 3 H); 2.90 (d, 1 H, J = 11.0 Hz);
3.04 (d, 1 H, J = 10.3 Hz); 3.19—3.60 (m, 8 H); 12.24 (br.s, 2 H).
Nꢀ[6ꢀ(3ꢀMethoxypropyl)ꢀ4,8ꢀdinitroꢀ4,5,6,7,8,9ꢀhexahydroꢀ
4,8ꢀmethano[1,3]thiazolo[4,5ꢀd]azocinꢀ2ꢀyl]acetamide (13b).
The yield was 49%, m.p. 200—201 C. Found (%): C, 44.93;
H, 5.69; N, 17.78. C15H21N5O6S. Calculated (%): C, 45.11;
H, 5.30; N, 17.53. 1H NMR, : 1.49 (m, 2 H); 2.09 (s, 3 H);
2.46—2.54 (m, 2 H); 2.64 (d, 1 H, J = 10.4 Hz); 2.75 (d, 1 H,
J = 10.5 Hz); 2.85—2.99 (m, 4 H); 3.03 (s, 3 H); 3.12—3.39
(m, 3 H); 3.58 (d, 1 H, J = 16.6 Hz); 12.20 (br.s, 1 H). IR, /cm–1
:
685, 1077, 1122, 1267, 1343, 1369, 1547, 1693, 2828, 2939,
3163, 3424.
Nꢀ(6ꢀEthylꢀ4,8ꢀdinitroꢀ4,5,6,7,8,9ꢀhexahydroꢀ4,8ꢀmethꢀ
ano[1,3]thiazolo[4,5ꢀd]azocinꢀ2ꢀyl)acetamide (13c). The yield
was 69%, m.p. 149—150 C. Found (%): C, 43.66; H, 5.09;
N, 19.82. C13H17N5O5S. Calculated (%): C, 43.94; H, 4.82;
1
N, 19.71. H NMR, : 0.86 (t, 3 H, J = 6.9 Hz); 2.09 (s, 3 H);
2.44—2.55 (m, 2 H); 2.60 (d, 1 H, J = 10.7 Hz); 2.76 (d, 1 H,
J = 10.4 Hz); 2.91 (d, 1 H, J = 11.0 Hz); 3.19 (t, 2 H, J = 10.2 Hz);
3.33—3.39 (m, 2 H); 3.58 (d, 1 H, J = 16.7 Hz); 12.23 (s, 1 H).
Nꢀ[6ꢀ(2ꢀMethoxyethyl)ꢀ4,8ꢀdinitroꢀ4,5,6,7,8,9ꢀhexahydroꢀ
4,8ꢀmethano[1,3]thiazolo[4,5ꢀd]azocinꢀ2ꢀyl]acetamide (13d).
The yield was 65%, m.p. 165—165 C. Found (%): C, 43.55;
H, 5.11; N, 18.04. C14H19N5O6S. Calculated (%): C, 43.63;
H, 4.97; N, 18.17. 1H NMR, : 2.09 (s, 3 H); 2.57—2.78 (m, 3 H);

1,5ꢀDinitroꢀ3ꢀazabicyclo[3.3.1]nonanes
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 3, March, 2012
599
2.91 (t, 1 H, J = 10.0 Hz); 3.11 (s, 3 H); 3.18—3.41 (m, 7 H);
3.57 (d, 1 H, J = 16.2 Hz); 12.23 (s, 1 H).
Chem. Bull., Int. Ed., 2008, 57, 1539]; 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, 414].
2. N. S. Zefirov, S. V. Rogozina, Usp. Khim., 1973, 42, 423
[Russ. Chem. Rev. (Engl. Transl.), 1973, 42, 190].
3. N. N. Yarmukhamedov, L. T. Karachurina, R. Yu. Khisaꢀ
mutdinova, F. S. Zarudnii, N. Z. Baibulatova, F. N. Dzhakꢀ
hangirov, V. A. Dokichev, Yu. V. Tomilov, M. S. Yunusov,
O. M. Nefedov, Pat. RF 2228334, on 22.07.2002; Byul. Izoꢀ
bret. [Inventor Bull.], 2004, No. 13 (in Russian).
4. T. Severin, R. Schmitz, M. Adam, Chem. Ber., 1963,
96, 3076.
5. T. Severin, J. Loske, D. Scheel, Chem. Ber., 1969, 102, 3909.
6. K. J. Blackall, D. Hendry, R. J. Pryce, S. M. Roberts,
J. Chem. Soc., Perkin Trans 1, 1995, 2767.
7. I. E. Yakunina, I. V. Shakhkel´dyan, Yu. M. Atroshchenko,
A. S. Rybakova, N. A. Troitskii, E. V. Shuvalova, Zh. Org.
Khim., 2005, 41, 1259 [Russ. J. Org. Chem. (Engl. Transl.),
2005, 41, 1238].
Nꢀ(6ꢀMethylꢀ4,8ꢀdinitroꢀ4,5,6,7,8,9ꢀhexahydroꢀ4,8ꢀmethꢀ
ano[1,3]thiazolo[4,5ꢀd]azocinꢀ2ꢀyl)propanamide (14a). The
yield was 69%, m.p. 248—249 C. Found (%): C, 44.05; H, 5.02;
N, 19.43. C13H17N5O5S. Calculated (%): C, 43.94; H, 4.82;
N, 19.71. 1H NMR, : 1.04—1.16 (m, 4 H); 2.27 (s, 2 H);
2.34—2.42 (dd, 2 H, J = 7.4 Hz, J = 14.9 Hz); 2.50—2.54
(m, 1 H); 2.66 (d, 1 H, J = 10.3 Hz); 2.88 (d, 1 H, J = 10.9 Hz);
3.17 (t, 2 H, J = 12.3 Hz); 3.32—3.34 (m, 1 H); 3.40 (d, 1 H,
J = 16.8 Hz); 3.58 (d, 1 H, J = 16.6 Hz); 12.12 (s, 1 H).
Nꢀ[6ꢀ(3ꢀMethoxypropyl)ꢀ4,8ꢀdinitroꢀ4,5,6,7,8,9ꢀhexahydroꢀ
4,8ꢀmethano[1,3]thiazolo[4,5ꢀd]azocinꢀ2ꢀyl]propanamide (14b).
The yield was 58%, m.p. 134—135 C. Found (%): C, 46.65;
H, 5.41; N, 16.85. C16H23N5O6S. Calculated (%): C, 46.48;
H, 5.61; N, 16.94. 1H NMR, : 1.05—1.15 (m, 5 H); 1.49 (d, 2 H,
J = 5.7 Hz); 2.38 (dd, 2 H, J1 = 7.4 Hz, J2 = 14.9 Hz); 2.48—2.52
(m, 1 H); 2.64 (d, 1 H, J = 10.4 Hz); 2.75 (d, 1 H, J = 10.5 Hz);
2.92 (d, 1 H, J = 11.3 Hz); 2.98 (d, 1 H, J = 6.4 Hz); 3.03
(s, 3 H); 3.14 (d, 1 H, J = 10.2 Hz); 3.23 (d, 1 H, J = 11.1 Hz);
3.31—3.33 (m, 1 H); 3.36 (d, 1 H, J = 17.4 Hz); 3.59 (d, 1 H,
J = 16.6 Hz); 12.18 (s, 1 H). IR, /cm–1: 1114, 1183, 1264, 1344,
1545, 1694.
8. V. V. Poroikov, D. A. Filimonov, Yu. V. Borodina, A. A.
Lagunin, A. Kos, J. Chem. Inf. Comput. Sci., 2000, 40, 1349.
9. E. M. Asadulina, M. A. Bastrakov, V. V. Kachala, A. M.
Starosotnikov, S. A. Shevelev, Mendeleev Commun., 2008,
213; E. M. Asadulina, M. A. Bastrakov, A. M. Starosotꢀ
nikov, V. V. Kachala, S. A. Shevelev, Izv. Akad. Nauk,
Ser. Khim., 2009, 413 [Russ. Chem. Bull., Int. Ed., 2009,
58, 421].
[4,8ꢀDinitroꢀ2ꢀ(propionylamino)ꢀ4,7,8,9ꢀhexahydroꢀ4,8ꢀ
methano[1,3]thiazolo[4,5ꢀd]azocinꢀ6(5H)ꢀyl]acetic acid (14c).
The yield was 40%, m.p. 237—238 C. Found (%): C, 41.99;
H, 4.41; N, 17.61. C14H17N5O7S. Calculated (%): C, 42.10;
1
H, 4.29; N, 17.54. H NMR, : 1.05 (t, 3 H, J = 7.4 Hz); 2.38
(q, 2 H, J = 7.5 Hz); 2.89 (d, 1 H, J = 11.0 Hz); 3.03 (d, 1 H,
J = 10.5 Hz); 3.19—3.46 (m, 7 H); 3.58 (d, 1 H, J = 16.6 Hz);
12.18 (s, 1 H); 12.42 (br.s, 1 H).
10. A. M. Starosotnikov, A. V. Lobach, V. V. Kachala, S. A.
Shevelev, Izv. Akad. Nauk, Ser. Khim., 2004, 557 [Russ. Chem.
Bull., Int. Ed., 2004, 53, 584].
Nꢀ[6ꢀ(2ꢀMethoxyethyl)ꢀ4,8ꢀdinitroꢀ4,5,6,7,8,9ꢀhexahydroꢀ
4,8ꢀmethano[1,3]thiazolo[4,5ꢀd]azocinꢀ2ꢀyl]propanamide (14d).
The yield was 50%, m.p. 130—132 C. Found (%): C, 45.33; H, 5.41;
N, 17.88. C15H21N5O6S. Calculated (%): C, 45.11; H, 5.30;
N, 17.53. 1H NMR, : 1.05 (s, 3 H); 2.38 (d, 2 H, J = 6.9 Hz);
2.50—2.78 (m, 3 H); 2.90 (t, 1 H, J = 10.0 Hz); 3.11 (s, 3 H);
3.21—3.41 (m, 7 H); 3.57 (d, 1 H, J = 16.6 Hz); 12.18 (s, 1 H).
11. A. M. Kuvshinov, V. I. Gulevskaya, V. V. Rozhkov, S. A.
Shevelev, Synthesis, 2000, 1474; D. A. Brovko, V. N.
Marshalkin, V. V. Semenov, Khim. Geterotsikl. Soedin.,
2001, 552 [Chem. Heterocycl. Compd. (Engl. Transl.), 2001,
37, 504].
12. E. Buncel, M. R. Crampton, M. J. Strauss, F. Terrier, Elecꢀ
tron Deficient Aromaticꢀ and Heteroaromaticꢀbase Interactions,
Elsevier, Amsterdam, 1984, p. 422.
We thank T. G. Tolstikova and coꢀworkers (N. N.
Vorozhtsov Novosibirsk Institute of Organic Chemistry of
the Siberian Branch of the Russian Academy of Sciences)
for performing calculations of the potential biological acꢀ
tivity of 1,5ꢀdinitroꢀ3ꢀazabicyclo[3.3.1]nonane derivatives.
13. J. W. Dehn, R. Eltonhead, R. A. Pizzarello, US Pat. 3057848;
http://worldwide.espacenet.com/publicationDetails/bibꢀ
lio?CC=US&NR=3057848A&KC=A&FT=D&ND=6&ꢀ
date=19621009&DB=worldwide.espacenet.com&localeꢀ
=en_EP.
References
1. M. A. Bastrakov, A. M. Starosotnikov, A. Kh. Shakhnes,
Received March 9, 2011;
S. A. Shevelev, Izv. Akad. Nauk, Ser. Khim., 2008, 1508 [Russ.
in revised form September 27, 2011