3-Azabicyclo[3.3.1]nonane derivatives: IV. Synthesis of amino acids with 3-azabicyclo[3.3.1]nonane fragment

Article abstract of DOI:10.1023/A:1012402523702

A series of 1.5-dinitro-3-azabicyclo[3.3.1]non-6-enes was prepared by reduction of 1-R-2,4-and 1-R-3,5-dinitrobenzenes with potassium borohydride followed by Mannich reaction with formaldehyde and amino acids. The molecular structure of (6-bromo-1,5-dinitro-3-azabicyclo[3.3.1]non-6-en-3-yl)acetic acid was studied by X-ray diffraction analysis. The mechanism of decomposition under electron impact was determined for (7-methoxy-1,5-dinitro-3-azabicyclo[3.3.1]non-6-en-3-yl)acetic acid.

Full text of DOI:10.1023/A:1012402523702

Russian Journal of Organic Chemistry, Vol. 37, No. 4, 2001, pp. 583 591. Translated from Zhurnal Organicheskoi Khimii, Vol. 37, No. 4, 2001,
pp. 617 625.
Original Russian Text Copyright
,
2001 by Shakhkel dyan, Nikiforova, Grudtsyn, Atroshchenko, Borbulevich, Efremov, Gitis, Moiseev, Alifanova,
Chudakov, Kovalevskii.
3-Azabicyclo[3.3.1]nonane Derivatives: IV.* Synthesis
of Amino Acids with 3-Azabicyclo[3.3.1]nonane Fragment**
I. V. Shakhkel,dyan1, E. G. Nikiforova1, Yu. D. Grudtsyn1, Yu. M. Atroshchenko1,
O. Ya.Borbulevich2, Yu. A. Efremov1, S. S. Gitis1, D. N. Moiseev1, E. N. Alifanova1,
P. V. Chudakov1, and A. Yu. Kovalevskii2
1Lev Tolstoi Tula State Pedagogical University, Tula, 300600 Russia
2Nesmeyanov Institute of Organoelemental Compounds, Russian Academy of Sciences, Moscow, Russia
Received November 15, 1999
Abstract A series of 1.5-dinitro-3-azabicyclo[3.3.1]non-6-enes was prepared by reduction of 1-R-2,4- and
1-R-3,5-dinitrobenzenes with potassium borohydride followed by Mannich reaction with formaldehyde and
amino acids. The molecular structure of (6-bromo-1,5-dinitro-3-azabicyclo[3.3.1]non-6-en-3-yl)acetic acid
was studied by X-ray diffraction analysis. The mechanism of decomposition under electron impact was
determined for (7-methoxy-1,5-dinitro-3-azabicyclo[3.3.1]non-6-en-3-yl)acetic acid.
Azaanalogs of bicyclo[3.3.1]nonane are known to
possess biological activity [2]. On the other hand the
amino acids as necessary components of the living
body also are interesting physiologically active
substances. Among their synthetic derivatives were
found compounds with characteristics of important
farmaceuticals [3]. In this connection it seemed
interesting to prepare derivatives of azabicyclo-
[3.3.1]nonane containing in their structure amino acid
fragments.
tion was performed without isolation of the hydride
diadducts from the reaction mixture. The target
products were obtained at adding double excess of
formaldehyde and glycine (molar ratio of m-nitro-
benzene CH2O-amino acid 1: 4: 2). The further
increase in amount of aminomethylating reagents does
not result in notable increase in the yield of com-
pounds I; their yield is lower when the reaction is
carried out with substituted m-dinitrobenzene dis-
regarding the character of the substituent.
We formerly synthesized (1,5-dinitro-3-azabicyclo-
[3.3.1]non-6-en-3-yl)acetic acid starting with hydride
complex of m-dinitrobenzene prepared from the nitro
compound and potassium borohydride, then introduc-
ing it into Mannich reaction with formaldehyde and
aminoacetic acid [4]. Similarly from hydride adducts
of 1-R-2,4- and 1-R-3,5-dinitrobenzenes we prepared
compounds Ia k (see the Scheme).
The structure and composition of compounds
obtained was established from IR and 1H NMR
spectra and elemental analyses (Tables 1 3). In the
IR spectra of compounds Ia k (Table 3) are observed
absorption bands in the region 2500 3400 ( OH),
2830 2990 ( C H aliph.), 1710 1755 ( C=O),
1
1340 1380 and 1540 1560 cm
(
and
NO2).
s
as
1
In analysis of H NMR spectra (300 MHz) of
compounds I (Table3, Fig.1) we regarded piperidine
ring as having chair conformation with no eclipsed
positions, and the cyclohexene fragment as being
close to planar. In all structures the methylene
protons H8 are nonequivalent due to dissimilar
localization with respect to the equatorial plane of the
piperidine ring and to the nitro group at C1 atom. The
methylene groups protons are coupled with a geminal
constant 17.5 18,5 Hz. In the spectra of compounds
Ia d the signal of each such proton appears as a
doublet of doublets due to the coupling with the H7
proton (3J 3.5 Hz). The signal of H7 proton is split
into a doublet of doublets or into a triplet. The
The reduction of nitro compounds with KBH4 was
carried out in a mixture THF water (1: 1 by volume)
ensuring sufficient solubility of both reagents. The
optimum temperature is within 10 20 C range
providing both fair reduction rate and preventing
decomposition of the arising dipotassium salts of
3,5-bis(aci-nitro)cyclohex-1-ene. The aminomethyla-
*
Communication III see [1].
The study was carried out under financial support of the
**
Russian
Foundation
for
Basic
Research
(grant
no. 97-03-33783), and of the Program Supporting the Lead-
ing Scientific Schools (grant no. 96-15-97367).
1070-4280/01/3704-0583$25.00 2001 MAIK Nauka/Interperiodica

584
SHAKHKEL,DYAN et al.
Scheme.
R1 = CH3, R2 = H, R3 = CH2COOH (a), R1 = Cl, R2 = H, R3 = CH2COOH (b), R1 = Br, R2 = H, R3 =
CH2COOH (c), R1 = OCH3, R2 = H, R3 = CH2COOH (d), R1 = H, R2 = OCH3, R3 = CH2COOH (e), R1 = H, R2 =
COOH, R3 = CH2COOH (f), R1 =
H, R2 = COOCH3, R3 = CH2COOH (g), R1 = H, R2 = CONH2, R3 =
CH2COOH (h), R1 = H, R2 = CON(C2H5)2, R3 = CH2COOH (i), R1 = H, R2 = piperidinocarbonyl, R3 =
CH2COOH (j), R1 = H, R2 = morpholinocarbonyl, R3 = CH2COOH (k), R1 = R2 = H, R3 = CH2CH2COOH (l),
R1 = R2 = H, R3 = CH(COOH)CH2COOH (m), R1 = R2 = H, R3 = CH(COOH)CH2CONH2 (n), R1 = R2 =
H, R3
= CH(COOH)CH2CH2COOH (o).
Table 1. Yields, melting points, retention factors, and elemental analyses of compounds Ia o
Found, %
Calculated,
%
Compd.
Yield, % mp,
C
R
Formula
f
no.
C
H
N
C
H
N
Ia
38
23
36
33
26
40
42
30
36
38
48
53
28
19
32
167 168
172 173
176 177
185 186
192 193
219 220
170 171
234 235
169 170
203 205
242 244
223 224
224 225
159 160
166 167
0.61
0.67
0.62
0.65
0.67
0.43
0.60
0.23
0.63
0.65
0.59
0.55
0.42
0.13
0.46
46.42, 5.23, 14.70,
46.27 5.34 14.70
39.48, 4.00, 14.00,
39.33 3.79 13.89
34.60, 3.66, 12.10,
34.38 3.74 12.12
43.57, 5.32, 14.03,
43.60 5.11 14.10
43.97, 5.45, 14.02,
43.72 5.25 14.12
42.20, 4.58, 13.38,
41.95 4.49 13.31
43.91, 4.67, 12.84,
43.89 4.66 12.79
42.61, 4.93, 18.05,
42.53 4.72 17.98
48.98, 5.72, 15.24,
49.24 5.89 15.31
50.76, 5.88, 14.75,
50.57 5.79 14.80
47.01, 5.37, 14.62,
46.96 5.32 14.64
46.18, 5.42, 14.85,
46.55 5.31 14.64
45.00, 4.65, 12.70,
44.75 4.77 12.75
44.09, 4.98, 17.03,
43.72 4.95 16.89
45.25, 4.93, 11.96,
46.39 5.01 12.19
C11H15N3O6
C10H12ClN3O6
C10H12BrN3O6
C11H15N3O7
C11H15N3O7
C11H13N3O8
C12H15N3O8
C11H14N4O7
C15H22N4O7
C16H22N4O7
C15H20N4O8
C11H15N3O6
C12H15N3O8
C12H16N4O7
C13H17N3O8
46.32
39.29
34.31
43.86
43.86
41.91
43.77
42.04
48.65
50.26
46.88
46.32
43.77
43.90
45.48
5.30
3.96
3.46
5.02
5.02
4.16
4.59
4.49
5.99
5.20
5.25
5.30
4.56
4.91
4.99
14.73
13.75
12.00
13.95
13.95
13.33
12.76
17.83
15.13
14.65
14.58
14.73
12.77
17.07
12.24
Ib
Ic
Id
Ie
If
Ig
Ih
Ii
Ij
Ik
Il
Im
In
Io
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 4 2001

3-AZABICYCLO[3.3.1]NONANE DERIVATIVES: IV.
585
1
Table 2. IR spectra, cm , of compounds Ia o
Compd.
no.
s (NO2)
as (NO2)
(C=O)
(O H)
(C H aliph.)
Other bands
Ia
Ib
Ic
Id
Ie
If
1347
1546
1716
1721
1721
1713
1720
1708
1727
1665, 1702
2500 3200 2836, 2893, 2980
2500 3300 2867, 2923, 2951
2700 3300 2859, 2925, 2963
2600 3300 2856, 2927
2500 3200 2836, 2913, 2964
2700 3400 2873, 2955
1356, 1377
1349, 1374
1340, 1383
1340, 1373
1340
1565
1551
1539
1544
1535
1541
1540
Ig
Ih
1360, 1381
1343
2500 3400 2856, 2921, 2960
2600 3300 2852, 2927, 2956
1633 [ (NH2)]; 3365,
3469 [ (NH2)]
Ii
Ij
Ik
Il
Im
In
1356, 1377
1351, 1367
1357
1340
1363
1546, 1593
1541, 1589
1549, 1569
1535
1553
1531
1735
1733
1732
1724
1717
1700
2500 3300 2845, 2940, 2973
2500 3200 2867, 2947
2700 3400 2859, 2922
2500 3100 2877, 2928
2750 3300 2873, 2937
2500 3400 2867, 2927
1356
1657 [ (NH2)]; 3200,
3347, 3443 [ (NH2)]
Io
1363
1547
1719
2500 3400
2959
Table 3. 1H NMR spectra, , ppm (J, Hz) (CCl4 DMSO-d6) of compounds Ia k
Compd.
He2
Ha2
He4
Ha4
H6 (H7)
5.71 m
He8
Ha8
no.
Ia
3.27 d
(11.2)
3.25 d
(11.2)
3.20 d
(11.2)
3.27 d
(11.1)
3.05 d
(11.1)
3.20 d
(10.5)
3.21 d
(11.2)
3.17 d
(11.2)
3.20 d
(11.2)
3.21 d
(10.5)
3.22 d
(10.5)
3.02 d
(11.1)
3.15 d
(11.1)
3.11 d
(10.5)
3.03 d
(11.1)
3.00 d
(11.1)
3.14 d
(10.5)
3.17 d
(11.2)
3.11 d
(11.2)
3.08 d
(11.2)
3.04 d
(10.5)
2.97 d
(10.5)
3.31 d
(11.1)
3.36 d
(11.1)
3.36 d
(10.5)
3.35 d
(11.1)
3.34 d
(11.2)
3.37 d
(10.5)
3.37 d
(10.5)
3.36 d
(10.5)
3.43 d
(10.6)
3.40 d
(10.5)
3.40 d
(10.5)
2.97 d
(11.2)
3.03 d
(11.2)
3.04 d
(11.2)
2.96 d
(11.1)
3.01 d
(11.2)
3.07 d
(10.5)
3.08 d
(10.5)
3.05 d
(10.7)
3.03 d
(10.6)
3.00 d
(10.5)
2.93 d
(10.5)
2.77 m
2.70 m
Ib
Ic
Id
Ie
If
6.22 d.d
(4.6, 3.5)
6.41 d.d
(4.6, 3.6)
4.95 t
2.99 d.d
(18.3, 3.5)
2.96 d.d
(18.4, 3.6)
2.86 d.d
(17.7, 2.6)
2.83 d
(17.7)
2.98 d
(18.4)
3.00 d
(18.4)
2.98 d
(18.4)
3.00 d
(18.3)
2.99 d
(18.4)
3.01 d
(17.7)
2.83 d.d
(18.3, 4.6)
2.79 d.d
(18.4, 4.6)
2.75 d.d
(17.7, 3.9)
2.72 d
(17.7)
2.86 d
(18.4)
2.93 d
(18.4)
2.85 d
(18.4)
2.77 d
(18.3)
2.78 d
(18.4)
2.78 d
(17.7)
(3.38)
5.00 s
6.96 s
7.03 s
6.76 s
5.95 s
5.94 s
6.01 s
Ig
Ih
Ii
Ij
Ik
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 4 2001

586
SHAKHKEL,DYAN et al.
Table 3 (Contd.)
Compd.
no.
He9
Ha9
H
H
COOH
R1 (R2)
Ia
Ib
Ic
Id
Ie
If
2.94 d
(11.2)
3.15 d
(11.2)
3.14 d
(11.1)
3.12 d
(11.1)
2.75 d
(11.2)
2.81 d
(11.8)
2.53 d
(11.2)
2.78 d
(11.2)
2.80 d
(11.1)
2.56 d
(11.1)
2.63 d
(11.2)
2.73 d
(11.8)
3.45 d
(17.1)
3.52 d
(17.1)
3.52 d
(17.1)
3.46 d
(17.7)
3.49 d
(17.7)
3.47 d
(17.7)
3.38 d
(17.1)
3.47 d
(17.1)
3.41 d
(17.1)
3.37 d
(17.7)
3.37 d
(17.7)
3.36 d
(17.7)
12.26 s
12.32 s
12.35 s
12.28 s
12.23 s
12.48 s
1.58 s (3H)
3.53 s (3H)
3.59 s (3H)
12.48 s
Compd.
no.
He9
Ha9
H
H
COOH
R1 (R2)
Ig
Ih
Ii
2.81 d
(11.8)
2.80 d
(11.2)
2.84 d
(11.2)
2.85 d
(11.2)
2.86 d
(11.2)
2.75 d
(11.8)
2.68 d
(11.2)
2.73 d
(11.2)
2.73 d
(11.2)
2.73 d
(11.2)
3.46 d
(17.7)
3.48 d
(17.7)
3.48 d
(17.7)
3.46 d
(17.7)
3.43 d
(17.7)
3.35 d
(17.7)
3.37 d
(17.7)
3.38 d
(17.7)
3.36 d
(17.7)
3.35 d
(17.7)
12.29 s
12.30 s
12.35 s
12.33 s
12.32 s
3.76 s (3H)
7.00 s (1H, NH),
7.45 s (1H, NH‘)
1.12 t (3H, CH3),
3.44 q (2H, CH2, 7.2)
1.54 m, 1.64 m, 3.51 m
Ij
Ik
3.58 m
abnormal chemical shift ot this proton in the spectrum
of compound Id ( 4.95 ppm) is probably caused by
the additional screening by a methyl group fixed
in a syn-configuration. In the spectra of compounds
resulting in the downfield shift of the corresponding
doublet as compared with its position in the spectra
of compounds Ie k. As in the same plane should be
located two carbon and two oxygen atoms we believe
that the carboxymethyl group at the nitrogen atom in
compounds Ia k cannot be present in the endo-con-
figuration. The methylene protons therein become
nonequivalent due to asymmetrical position with
respect to the C2NC4 plane, and their signals are split
into doubles by the mutual coupling with the constant
2J 17.1 17.7 Hz. The broad singlet from the carboxy
group proton is located in the 12.2 12.5 ppm region.
The protons from R substituents give the expected
signals. In the spectrum of compound Ih the amide
group protons are nonequivalent due to no free rota-
tion around C N bond because of a hydrogen bond
between one of these protons and one oxygen of a
4
Ie k the constants J6,8 are apparently small, and thus
the signal of H6 proton is observed as a slightly
broadened singlet. The upfield chemical shift of the
signal from proton H6 in the spectrum of compound
Ie ( 5.00 ppm) also may be caused by additional
screening with a methyl group. The signals of
methylene protons in positions 2, 4, and 9 of the
piperidine ring appear as three pairs of broadened
doublets from equatorial and axial protons (2J 10.5
4
11.5 Hz) since the coupling constants J are close to
the resolution limit of the NMR spectrometer. The
doublets at
3.35 3.40 ppm were assigned to He4
protons that suffer the strongest anisotropic effect
from the double bond. The chemical shifts of all the
doublets are also affected by the torsion angles of the
nitro groups. In compounds Ia d the R1 substituent
effects a deshielding influence on the H9e proton
1
nitro group attached to C4 carbon. Thus the H NMR
spectra confirm the structure of compounds syn-
thesized.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 4 2001

3-AZABICYCLO[3.3.1]NONANE DERIVATIVES: IV.
587
1
Fig. 1. H NMR spectrum (CCl4 DMSO-d6) (300 MHz) of (6-bromo-1,5-dinitro-3-azabicyclo[3.3.1]non-6-en-3-yl)acetic acid (Ic).
The series of the bicyclo[3.3.1]nonanes syn-
thesized was extended by using in the Mannich
condensation of the other amino acids: 9 -alanine,
DL-asparagine, DL-aspartic acid, D,L-glutamic acid).
Thus we synthesized compounds Il o. The struc-
ture thereof also follows from the spectral data
(Tables 2, 4). In the 1H NMR spectra of these
compounds the signals of protons H6 and H7 appear
at 5.87 5.97 ppm (J6,7 10 Hz) respectively, and
those from the carboxy group in the region 11.95
12.53 ppm. A specific feature of the spectra of com-
pounds Im o is a double set of signals from H
proton of the substituent attached to nitrogen. This is
due to the existence of stereoisomers differing in the
position of this proton with respect to the equatorial
plane of the piperidine ring. In all conformers are
also different the chemical shifts of H4e protons
(Table 4).
To prove the structures of bicyclo[3.3.1]nonanes
we also carried out a ray diffraction study of one
among the compounds synthesized, (6-bromo-1,5-di-
nitro-3-azabicyclo[3.3.1]non-6-en-3-yl)acetic acid (Ic)
Fig. 2. Molecular structure of (6-bromo-1,5-dinitro-3-
azabicyclo[3.3.1]non-6-en-3-yl)acetic acid (Ic).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 4 2001

588
Table 4. 1H NMR spectra , ppm (J, Hz) (CCl4 DMSO-d6) of compounds Il o
SHAKHKEL,DYAN et al.
Compd.
no.
He2
Ha2
He4
Ha4
H6
H7
He8
Ha8
Il
3.07 d
(10.2)
3.18 d
(10.1)
2.70 d
(10.2)
2.82 d
(10.1)
3.31 d
(10.2)
3.35 d
(10.6),
3.29 d
(10.6)
2.65 d
(10.2)
2.72 d
(10.6)
5.92 d
(10.4)
5.87 d
(10.0)
5.98 d.t
(10.4, 3.1)
5.97 d.t
2.75 d
(16.5)
3.06 d.d
2.68 d
(16.5)
2.82 d.d
(16.2, 2.4)
Im
(10.0, 2.4) (16.2, 2.4)
In
Io
3.15 d
(10.3)
2.72 d
(10.3)
3.35 d
(10.6),
3.33 d
(10.6)
3.27 m
(11.0)
2.65 d
(10.6)
5.87 m
(10.0)
5.96 m
(10.0)
2.74 d
(16.0)
2.66 d
(16.0)
3.05 m
(10.2)
2.72 d
(10.2)
3.17 m
(11.0)
5.97 d
(10.0)
6.06 m
(10.0)
2.78 d
(15.0)
2.72 d
(15.0)
Compd.
no.
He9
Ha9
H
H
H
Xa
Yb
Il
Im
2.71 d (10.2) 2.65 d (10.2)
3.05 d (10.4) 2.65 d (10.4)
2.85 m
3.80 d.d
2.36 t (7.0) 2.36 t (7.0)
2.82 m 11.95 s
12.35 12.35 s
2.65 d.d
2.39 d.d
(8.1, 6.8),
3.71 d.d
(16.0, 6.8)
(16.0, 8.1)
(8.1, 6.8)
3.84 t (7.1),
3.76 t (8.5)
3.44 d.d
(10.6, 5.0),
3.30 d.d
In
Io
3.09 d (11.1) 3.04 d (11.1)
2.90 d (10.6) 2.68 d (10.6)
2.45 d.d
(15.0, 7.1)
1.91 m
2.36 d.d
(15.0, 8.5)
1.80 m
12.53 s 7.26 s, 7.15 s,
6.65 s, 6.60 s
12.17 s 12.17 s, 2.26 t
(7.2)
(10.6, 5.6)
a
b
X = H (Il), COOH (Im o).
X = COOH (l, m, o), CONH2 (n).
(Fig. 2). The piperidine ring in compound Ic is in the
chair conformation. The deviations of atoms N3 and
C9 from the plane going through all the other atoms
of the ring amount to 0.667(5) and 0.759(5)
respectively. The cyclohexene fragment is in sofa
conformation with C9 deviating from the plane of the
other atoms by 0.770(5) . The conformation of the
eight-membered ring C1 C8 is similar to that
observed in analogous compounds [5 6]. The nitro
groups attached to atoms C1 and C3 have a synclinal
orientation with respect to the C1 C8 and C5 C6
bonds respectively [torsion angles C8C1N1O4 and
C6C5N2O6 are equal respectively to 54.4(5) and
57.6(5) ]. The nitrogen atom N3 is in the trigonal-
pyramidal configuration. Its deviation from the plane
going through three atoms linked thereto amounts
to 0.369(5)
[the sum of bond angles equals
341.5(4) ]. The CH2COOH group is in equatorial
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3-AZABICYCLO[3.3.1]NONANE DERIVATIVES: IV.
589
position [torsional angle C10N3C2C1 166.9(4) ] and
possesses a synclinal orientation with respect to
C2 N3 bond [torsional angle C2N3C10C11 64.4(5) ].
The carboxy group is oriented synperiplanar [torsional
angle N3C10C11O 2.8(7) ].
characteristic of nitro compounds [8] is relatively
weakly pronounced both at the first and the second
stage of the molecular ions degradation. Relative
intensity of peaks belonging to ions with m/z 271
[M NO]+ and 255 [M NO2 NO]+ in both cases cor-
responds to 0.1% of the total ion current. In the latter
fragment a hydrogen atom migrates from the bicycle
to the remaining oxygen of a nitro group. As a result
arises a hydroxy group whose cleavage from the
fragment [M NO]+ provides a relatively abundant ion
peak with m/z 208 of diene structure. The loss of a
CO2 molecule by the carboxymethyl group gives rise
of an ion peak of m/z 164, and the subsequent
cleavage of a CH2 species results in ions with m/z
150. This fragment ion undergoes a rearrangement
that results in formation of a C N bond between a
carbon in the bicycle and a nitrogen. Thus forms an
NCH2 group that is eliminated. This process is
energetically feasible to such extent that the resulting
ion peak of m/z 122 is the most abundant in the mass
spectrum of compound Ie. Note that no elimination of
methoxy group occurs at the electron impact either in
the first stage or in the further stages of the de-
composition of the molecular ions.
Compound Ic forms a crystal solvate with toluene
of 1: 1 composition; therewith the solvent is dis-
ordered by two positions with population density of
0.5. Thus the data of the X-ray structural analysis are
well consistent with the spectral data.
Additional proofs of the structure of azabicyclo-
nonanes synthesized we obtained from the study of
fragmentation under electron impact by an example of
(7-methoxy-1,5-dinitro-3-azabicyclo[3.3.1]non-6-en-
3-yl)acetic acid (Ie). Mass spectrum of compound Ie
revealed the low stability of the molecular ion to the
electron impact (Irel 1.5%). This fact is apparently
caused by easy rupture of the molecular ion in two
places: with elimination of a nitro and a carboxy
groups. Therewith in the mass spectrum are observed
fairly abundant fragment ions with m/z 255 [M NO2]+
and 256 [M COOH]+ . The nitro-nitrite rearrangement
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 4 2001

590
SHAKHKEL,DYAN et al.
1
Table 5. Coordinates ( 104) and equivalent isotropic
thermal parameters (
75IR. H NMR spectra were registered on spectro-
meter Bruker AC-300, mixed solvent CCl4 DMSO-
d6, internal reference HMDS. The retention factors
(Rf) were determined on Silufol UV-254 plates, eluent
toluene acetone (2: 1), development under UV ir-
radiation or in iodine vapor. Mass spectrum of
compound Ie was measured on Varian MAT-311
instrument, ionizing electrons energy 70 eV.
2
103) of nonhydrogen atoms in the
structure of (6-bromo-1,5-dinitro-3-azabicyclo[3.3.1]non-
6-en-3-yl)acetic acid (Ic)
Ueq
Atom
x
y
z
Br1
469(1)
9180(1)
6509(1)
7715(4)
5272(3)
8682(3)
9049(3)
10848(3)
6803(4)
8664(3)
5161(3)
4408(3)
7688(4)
8675(4)
7488(4)
6537(3)
6897(4)
7562(4)
8019(4)
6420(4)
9749(4)
9831(4)
38(1)
30(1)
26(1)
21(1)
33(1)
36(1)
62(1)
45(1)
39(1)
47(1)
22(1)
23(1)
22(1)
19(1)
24(1)
24(1)
27(1)
23(1)
25(1)
24(1)
N1
6445(5) 11354(4)
2283(5) 11764(4)
1678(4) 11494(3)
1120(4) 14066(3)
895(5) 13461(3)
7371(5) 12011(5)
6859(5) 10924(5)
1201(5) 12581(4)
3182(6) 11297(4)
4666(5) 11033(4)
3427(5) 11718(4)
1342(5) 11985(4)
2559(5) 11278(4)
2303(6)
3192(5)
4531(6)
4431(5) 11555(4)
373(5) 11832(4)
251(5) 13240(4)
General procedure of synthesis of 3-R3-6-R1-7-R2-
1,5-dinitro-3-azabicyclo[3.3.1]non-6-enes Ia o. In 10
ml of THF-water mixture (1: 1 by volume) was dis-
solved 0.4 mmol of dinitro compound. At cooling
with ice water and continuous stirring 1.08 g
(20 mmol) of KBH4 was added within 10 15 min,
and the stirring was carried out for 15 min more
maintaining the temperature of the reaction mixture
in 5 15 C range. After the end of the reduction was
added 1.5 ml of cooled 30% aqueous solution of
formaldehyde (16 mmol) and 8 mmol of an ap-
propriate amino acid in 50 ml of water, then the
reaction mixture was acidified with acetic acid to
pH 6. The separated precipitate of compounds Ij, l
was filtered off and crystallized from ethanol; with
the rest of the reaction products was performed
extraction with several portions of dichloroethane,
and the solvent was evaporated in a vacuum. The raw
products Ii, m o were dissolved in ethanol, the
solution was treated with activated carbon, filtered,
the filtrate was diluted with a double volume of
water, and the product was salted out with sodium
chloride. Compounds If, h were crystallized from an
acetone dichloroethane mixture, compound Ik from
a mixture acetone DMF. Compounds Ia e, g were
purified by column chromatography on silica gel
(ASKG) (eluent toluene acetone, 10: 1) followed by
crystallization from ethanol.
N2
N3
O1
O2
O3
O4
O5
O6
C1
C2
C4
C5
C6
9836(4)
9089(4)
9571(4)
C7
C8
C9
C10
C11
C1S (A)
C2S (A)
C3S (A)
C4S (A)
C5S (A)
C6S (A)
C7S (A)
C1S (B)
C2S (B)
C3S (B)
C4S (B)
C1S (C)
C2S (C)
C3S (C)
3108(40) 14135(39) 11491(22) 107(12)
4568(26) 14595(21) 10406(18)
84(7)
58(4)
76(5)
5782(23) 13865(14)
7132(21) 14340(20)
9680(15)
8654(15)
2754(68) 14657(49) 11563(49) 189(32)
3638(38) 13585(16) 11147(32) 115(16)
5044(32) 14049(28) 10138(27)
91(9)
67(5)
39(4)
45(3)
69(6)
55(7)
82(7)
76(7)
4202(23) 15587(19)
5845(26) 15161(24)
6188(22) 14762(10)
7897(27) 14271(17)
5133(34) 15181(22)
6788(30) 14751(17)
7021(26) 14383(26)
6354(17)
5785(16)
4648(12)
4080(16)
5847(23)
5311(27)
4173(23)
Elemental analyses, melting points, retention
factors (Rf), and yields of compounds obtained are
given in Table 1, IR and 1H NMR spectra in
Tables 2 4.
The assumed scheme of compound Ie degradation
under the electron impact also supports the structure
of the bicyclononanes obtained.
Crystals for the X-ray study were grown by slow
evaporation under isothermal conditions of a solution
of compound Ic in a mixture toluene acetone (10: 1).
Crystals of C10H12BrN3O6 C7H8 (toluene) at 163(2)
Thus the use of amino acids in the Mannich
condensation with hydride diadducts of m-dinitro-
benzene provides a possibility to prepare new deriv-
atives of 3-azabicyclo[3.3.1]nonane that can be
interesting as potential biologically active substances.
K triclinic, a 8.169(4), b 10.654(5), c 11.475(5)
78.35(4), 72.96(4), 86.13(4) , V 935.1(8)
,
,
3
crystal size 0.4 0.4 0.3 mm, space group P1, Z 2,
3
1
dcalc 1.571 g cm , F(000) 452, = 2.238 mm .
EXPERIMENTAL
The intensities of 3574 reflections (3316 in-
dependent, Rint 0.130) were measured on automatic
IR spectra (from a film prepared from acetone solu-
tion) were recorded on spectrophotometer Specord
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 4 2001

3-AZABICYCLO[3.3.1]NONANE DERIVATIVES: IV.
591
four-circle diffractometer Enraf Nonius CAD4
1973, vol. 42, no. 3, pp. 423 441.
3. Agababyan, A.G., Gevorgyan, G.A., and Mndzho-
yan, O.L., Usp. Khim., 1982, vol. 51, no. 4,
pp. 678 695.
4. Atroshchenko, Yu.M., Nikiforova, E.G., Gitis, S.S.,
Grudtsyn, Yu.D., Shishkin, O.V., Andrianov, V.F.,
and Shakhkel,dyan, I.V., Zh. Org. Khim., 1999,
vol. 35, no. 9, pp. 1339 1343.
5. Evans, E.H., Newson, A.T., March, L.A., No-
well, I.W., and Wasworth, A.H., J. Chem. Soc.
Perkin Trans. I, 1987, no. 1, pp. 137 141.
( -filter, MoK irradiation, /2 -scanning to 2
max
50 ). The data file obtained was subjected to profile
analysis by procedure [9] that considerably refined
the data quality.
The structure was solved by the direct method
with the use of software SHELXTL PLUS [10]. The
position of hydrogen atoms was geometrically refined
along rider model with a fixed Uiso = nUeq of a
nonhydrogen atom bonded to the given hydrogen
atom (n = 1.5 for hydrogen atoms in methylene and
carboxy groups, n = 1.2 for all the other hydrogen
atoms). In refining the disordered solvate toluene
molecules we introduced the restrictions for the
following bond lengths: C(Ar) C(Ar) 1.400(9) and
C(Ar) CH3 1.470(9) [11]. The refinement by F2 in
anisotropic approximation (307 parameters) for non-
hydrogen atoms by full-matrix least-squares proce-
dure for 3222 reflections was performed to R1 0.072
[for 3015 reflections with F> 4 (F)], wR2 0.192, S
1.12. The coordinates of nonhydrogen atoms are
presented in Table 5.
6. Shishkin, O.V., Atroshchenko, Yu.M., Gitis, S.S.,
Alifanova, E.N., and Shakhkeldyan, I.V., Acta
Cryst., C, 1998, vol. 54, no. 2, pp. 271 273.
7. Atroshchenko, Yu.M., Nikiforova, E.G., Shakhkel,-
dyan, I.V., Grudtsyn, Yu.D., Akhmedov, N.G., Ali-
fanova, E.N., Borbulevich, O.Ya., Shishkin, O.V.,
Gitis, S.S., and Kaminskii, A.Ya., Zh. Org. Khim.,
2000, vol. 36, no. 5, pp. 771 777.
8. Khmel,nitskii, R.A., Efremov, Yu.A., Drozd, V.N.,
and Kaminskii, A.Ya., Izv. TSKhA., 1975, no. 1,
pp. 203 207.
9. Strel,tsov, V. A. and Zavodnik, V. E., Kristallogra-
fiya, 1989, vol. 34, no. 6, pp. 1369 1375.
10. Sheldrick, G.M., SHELXTL PLUS. PC Version.
A System of Computer Programs for the Determina-
tion of Crystal Structure from X-ray Diffraction Data,
Siemens Analytical X-ray Instruments Inc., Germany,
1994.
REFERENCES
1. Leonova, O.V., Atroshchenko, Yu.M., Shakhkel,-
dyan, I.V., Gitis, S.S., Grudtsyn, Yu.D., Nikiforo-
va, E.G., Alekhina, N.N., Alifanova, E.N., Chuda-
kov, P.V., and Kaminskii, A.Ya., Zh. Org. Khim.,
2001, vol. 37, no. 3, pp. 421 425.
11. Allen, F.H., Kennard, O., Watson, D.G., Bram-
mer, L., Orpen, A.J., and Taylor, R., J. Chem. Soc.
Perkin Trans. II, 1987, no. 1, pp. 1 19.
2. Zefirov, N.S. and Rogozina, S.V., Usp. Khim.,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 4 2001