Features of reactions between (3,5-dioxo-4-azatricyclo-[5.2.1.0 2-endo,6-endo ]dec-8-en-4-yl)carboxylic acids and p-nitrophenyl azide

Article abstract of DOI:10.1134/S1070428009020146

Reactions were performed of (3,5-dioxo-4-azatricyclo[5.2.1.0 ^{2-endo,6-endo} ]dec-8-en-4-yl)carboxylic acids and their derivatives with p-nitrophenyl azide. A significant fact of the involvement of the carboxy group into the formation of aziridine ring was established and the intermolecular character of this process was confirmed. The structure of compounds synthesized was proved by IR and ¹H NMR spectra.

Full text of DOI:10.1134/S1070428009020146

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 2, pp. 234−241. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © I.N. Tarabara, Ya.S. Bondarenko, L.I. Kas'yan, 2009, published in Zhurnal Organicheskoi Khimii, 2009, Vol. 45, No. 2,
pp. 246−253.
Features of Reactions between (3,5-Dioxo-4-azatricyclo-
[5.2.1.02-endo,6-endo]dec-8-en-4-yl)carboxylic Acids
and p-Nitrophenyl Azide
I. N. Tarabara, Ya. S. Bondarenko, and L. I. Kas’yan
Dnepropetrovsk National University, Dnepropetrovsk, 49625 Ukraine
e-mail: cf@ff.dsu.dp.ua
Received May 6, 2008
Abstract—Reactions were performed of (3,5-dioxo-4-azatricyclo[5.2.1.02-endo,6-endo]dec-8-en-4-yl)carboxylic acids
and their derivatives with p-nitrophenyl azide. Asignificant fact of the involvement of the carboxy group into the
formation of aziridine ring was established and the intermolecular character of this process was confirmed. The
structure of compounds synthesized was proved by IR and 1H NMR spectra.
DOI: 10.1134/S1070428009020146
O
O
The reaction of organic azides with compounds
containing multiple bonds is extensively used in designing
various heterocyclic systems, in partcular, three-
membered and five-membered nitrogen heterocycles and
their numerous derivatives [1, 2].Among the unsaturated
substrates used in these reactions a special place belongs
to norbornene and its derivatives: due to the enhanced
reactivity of the strained double bond the reaction of these
compounds with azides proceeds especially readily and
as a rule takes a single route affording substituted
triazolines or aziridines depending on the structure (type)
of the applied azide. The readiness of this reaction makes
it possible to use it for analytical detection of strained
double bonds [3], and norbornene proper as a convenient
reagent for testing the reactions of new azides [4]. The
reactions of norbornene and its numerous derivatives with
aryl azides proceeds along the mechanism of [3+2]-
cycloaddition and in the most cases results in the formation
of the corresponding triazoline systems [5]; reactions with
azides containing electron-withdrawing substituents at the
azide function (sulfonyl-, carbonylazides etc.), as a rule
provide the corresponding aziridines or the products of
deeper transformations [2, 6].
O
N R
O
O
II
I
O
O
O
S
N
N
N
N R
Ar
N
N R
O
Ar
O
O
IV
III
[7] the possibility was demonstrated to transform
anhydride I into sophisticated polycyclic systems by
reactions with arylsulfonyl azides. The reactions of imides
II (R=Alk, Ar, Ht) with a series of aryl azides and
arylsulfonyl azides were used to synthesize new
heteropolycyclic compounds III and IV [8]. The behavior
of the other derivatives of anhydride I in reactions with
azides was not investigated and thus became the goal of
this study.
We chose as objects of the research (3,5-dioxo-4-
azatricyclo[5.2.1.02-endo,6-endo]dec-8-en-4-yl)carboxylic
acids, the known and obtained for the first time products
of endic anhydride (I) condensations with natural amino
acids [9–11] employed as valuable “building blocks” in
organic synthesis [12–14], and also their derivatives. The
Among the compounds with a strained double bond
included into a rigid bicyclic system a special attention
attracts endic anhydride (I); owing to the presence of
the reactive anhydride ring it is extensively used for
preparation organic compounds of versatile structure. In
234

FEATURES OF REACTIONS BETWEEN (3,5-DIOXO-4-AZATRICYCLO-...
235
Scheme 1.
Scheme 2.
O
N
N
N X
N
OH
O
O
p-NO2C6H4N3
Vа_Vj
O
1
CHCl3, boiling
3
5
10
8
2
6
O2N
9
N
4
11
O2N
N X
OH
7
O
O
VIа_VIj
In reactions of acids Va–Vj with azides in other
solvents (benzene, acetonitrile) only insignificant changes
in the yield of the corresponding aziridines was observed;
the reaction in chloroform at room temperature required
considerably longer time and resulted in lower yield of
aziridines.
synthesis of known (Va–Vc, Vi, Vj) and new (Vd–Vh)
acids was carried out by the previously developed
procedure consisting in boiling equimolar mixtures of
anhydride I and appropriate amino acids in the glacial
acetic acid [12]; the target products were obtained in a
good yield and a high purity (Scheme 1).
We studied by an example of acid Va the behavior of
its derivatives in reaction with p-nitrophenyl azide. By
reaction of acid Va with anhydrous methanol or ethanol
in the presence of catalytic quantity of phosphorus
oxychloride we obtained previously described esters VIIa
and VIIb [10, 13]. Using chloride of acid Va obtained by
standard procedure we synthesized amides VIIIa–VIIIc
described in [12] (Scheme 3).
p-Nitrophenyl azide synthesized by a known procedure
[15] was used as reagent. The reaction of azide with
acids Va–Vj was performed by boiling equivalent amounts
of reagents in anhydrous chloroform. Notwithstanding
the type of amino acid we obtained unexpectedly as the
only reaction products aziridines VIa–VIj (Scheme 2).
The formation of the aziridine ring in reactions of
norbornene and its various derivatives with common aryl
azides was possible only under special conditions: either
at sufficiently high temperature (therewith transformation
occurred with stable at common circumstances products
of [3+2]-cycloaddition), or under UV-irradiation of the
reaction mixtures [1, 2]. In both events the aziridines were
not the only reaction products.
It was established that in reactions of compounds VIIa,
VIIb, VIIIa–VIIIc with p-nitrophenyl azide under the
same conditions the only products obtained were the
corresponding triazolines IXa–IXe (Scheme 4).
Similar facts were reported in one of our recent papers:
synthesized from acid Va derivatives with sub-stituted
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 2 2009

TARABARA et al.
236
carbamide, carbamate, and carbamoyl fragments in
reaction with p-nitrophenyl azide yielded exclusively the
corresponding triazolines Xa–Xd [16] (Scheme 5).
1H NMR spectra. The main criteria determining the
character of the heterocycle formed (triazoline or
aziridine) are the multiplicity and the position of the signals
corresponding to the protons in this ring. In the spectra
of aziridines VIa–VIj due to the high symmetry of the
Conclusive proofs of the structure of heterocyclic
compounds synthesized was obtained by analysis of their
Scheme 3.
R = CH3 (a), C2H5 (b); R' = CH2Ph (a), C6H4Br-p (b), 2-thiazolyl (c).
Scheme 4.
O
O
OR
N
N
N
N
ï-NO2C6H4N3
VIIà, VIIb
O
CHCl3, boiling
O2N
IXà, IXb
O
O
NHR'
N
N
N
ï-NO2C6H4N3
VIIIà_VIIIb
N
CHCl3, boiling
O
O2N
Scheme 5.
IXc_IXe
R = CH3 (a), C2H5 (b); R' = CH2Ph (c), C6H4Br-p (d), 2- thiazolyl (e).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 2 2009

FEATURES OF REACTIONS BETWEEN (3,5-DIOXO-4-AZATRICYCLO-...
237
molecule the protons H8 and H10 are equivalent and
resonate in the region 3.1–3.2 ppm. The lack of splitting
of these signals that might be caused by the coupling
with the bridgehead protons H1, H7 indicates their endo-
orientation and does not contradict the knownAlder rule
of the exo-attack [17, 18]. The additional proof of the
exo-orientation of the formed heterocyclic fragment with
respect to the bicyclic framework is the essential
nonequivalence of the bridging protons and the upfield
shift of the signal of one of them (H11an) as compared to
the position of this signal in the spectra of the initial olefins.
The proton (H11an) is located directly over the plane of
the three-membered ring and suffered from the mag-
netically anisotropic effect of the latter.
close location of the olefin fragment and the carboxy
group the involvement of the latter in the process of
aziridine ring formation may be both inter- and intra-
molecular.
In order to test the assumption on the probable intra-
molecular involvement of the carboxy group we synthesiz-
ed acid XII with the exo-configuration of the substituted
imide fragment proceeding from exo-anhydride XI
obtained by the known method of endo-isomer I
isomerization [20] (Scheme 6). The investigation of the
behavior of acid XII in the reaction with p-nitrophenyl
azide showed that in this case also formed the
corresponding aziridine XIII. The structure of the latter
is confirmed by the appearance in its 1H NMR spectrum
of a two-proton singlet in the region 3.10 ppm belonging
to the protons H8, H10 of the aziridine ring.
Owing to the significant asymmetry of molecules of
compounds IXa–IXe caused by the presence of asym-
metrically substituted triazoline fragment their 1H NMR
spectra are essentially different from the aziridine spectra
and are characterized by the nonequivalence of the
skeleton protons (H2 and H6, H1 and H7, H8 and H12).
This nonequivalence is especially large for the protons
of the triazoline fragment (H2, H6) that resonate in the
regions 4.88–4.62 and 4.28–3.81 ppm; their coupling is
characterized by vicinal constants 8.6–9.4 Hz common
for the like systems containing an exo-oriented triazoline
fragment [19]. The exo-orientation of the formed triazo-
line ring is also confirmed by the strong nonequivalence
and by the position of the signals from the bridging protons
(H13s, H13an).
These data are likely to suggest that the participation
of the carboxy group in the aziridine formation is of the
intermolecular character. The additional proof of this type
of behavior was obtained by the reaction of ester VIIb
with p-nitrophenyl azide in the presence of acid Va. The
treatment of a mixture containing equivalent amounts of
compounds Va and VIIb with a slight excess p-nitro-
phenyl azide alongside aziridine VIa was obtained aziridine
XIV (Scheme 7) whose structure was proved by spectral
data.
Thus the study of unusual proceeding of reactions of
(3,5-dioxo-4-azatricyclo[5.2.1.02-endo,6-endo]dec-8-en-4-
yl)carboxylic acids with p-nitrophenyl azide made it
possible to propose a simple procedure for introducing
an aziridine ring into molecules of polycyclic framework
compounds. An intermolecular character of the carboxy
group participation in the aziridine ring formation was
confirmed.
The results obtained suggest that the carboxy group
is directly involved in the formation of the aziridine ring.
We believe that the product of [3+2]-cycloaddition form-
ed in the first stage suffers protonation that induces its
further transformation into aziridine. Owing to the con-
formational rigidity of the bicyclic framework and spatially
Scheme 6.
Δ
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TARABARA et al.
238
Scheme 7.
O
O
O
O
OEt
OH
+
N
N
O
O
VIIb
Vа
O
O
O
O
OEt
OH
п-NO2C6H4N3
N
N
N
N
O2N
O2N
+
CHCl3, boiling
O
VIa
O
XIV
3-Phenyl-3-(3,5-dioxo-4-azatricyclo[5.2.1.02-endo,6-endo]-
dec-8-en-4-yl)propanoic acid (Vg). Yield 85%, mp 85–
86°C (benzene), Rf 0.33 (ether). IR spectrum, cm–1: 3460,
EXPERIMENTAL
IR spectra were measured on a spectrophotometer
UR-20 from samples of compounds pelletized with KBr.
1H NMR spectra were registered on spectrometers
Bruker DAX-500 at operating frequency 500 MHz and
Varian VXR at operating frequencies 200 and 300 MHz,
internal reference TMS. The reaction progress was
monitored and the homogeneity of compounds obtained
was checked by TLC on Silufol UV-254 plates, eluents
ether and acetone, development in iodine vapor. Elemental
analyses were performed on an analyzer Carlo Erba.
(3,5-Dioxo-4-azatricyclo[5.2.1.02-endo,6-endo]dec-8-en-
4-yl)carboxylic acids Vd–Vh were synthesized by
procedure [12].
6-(3,5-Dioxo-4-azatricyclo[5.2.1.02-endo,6-endo]-dec-
8-en-4-yl)hexanoic acid (Vd). Yield 81%, oily substance,
Rf 0.43 (ether). IR spectrum, cm–1: 3510, 1760, 1735,
1700, 1240, 740. Calculated, %: C 64.98; H 6.86; N 5.05.
C15H19NO4. Found, %: C 65.17; H 6.71; N 5.15.
1
3080, 1760, 1720, 1700, 1590, 1260, 720. H NMR
spectrum (300 MHz, CDCl3), δ, ppm: 1.47 d (1H, H10an),
1.51 d (1H, H10s), 3.15 d (1H, CH), 3.17 d (1H, CH),
3.21 m (2H, H1, H7), 3.30 m (2H, H2, H6), 5.37 t (1H,
CH), 5.79 m (1H, H9), 5.90 m (1H, H8), 7.23–7.34 m
(5Harom), 12.38 s (1H, COOH). Calculated, %: C 69.44;
H 5.50; N 4.50. C18H17NO4. Found, %: C 69.19; H 5.44;
N 4.35.
2-(3,5-Dioxo-4-azatricyclo[5.2.1.02-endo,6-endo]-dec-
8-en-4-yl)-3-methylsulfanylbutanoic acid (Vh). Yield
87%, mp 64–65°C (2-propanol), Rf 0.69 (ether). IR
spectrum, cm–1: 3450, 3090, 1760, 1720, 1705, 1250, 725.
1H NMR spectrum (200 MHz, DMSO-d6), δ, ppm:
1.58 d (1H, H10an), 1.64 d (1H, H10s), 2.03 s (3H, CH3),
1.92–2.38 m (4H, 2CH2), 3.30 m (2H, H1, H7), 3.35 m
(2H, H2, H6), 4.47 t (1H, CH), 6.03 m (2H, H8, H9),
11.78 br.s (1H, COOH). Calculated, %: C 56.95; H 5.76;
N 4.75. C14H17NO4S. Found, %: C 56.70; H 5.61; N 4.44.
Reactionof(3,5-dioxo-4-azatricyclo[5.2.1.02-endo,6-endo]-
dec-8-en-4-yl)carboxylic acids and their derivatives
with p-nitrophenyl azide. General procedure. A mix-
ture of 0.003 mol of p-nitrophenyl azide and 0.003 mol of
an appropriate olefin in 10–15 ml of anhydrous chloroform
was boiled till the completion of the reaction (TLC
monitoring). On cooling the reaction mixture the separated
precipitate was filtered off, thoroughly washed with
chloroform on the filter, dried, and crystallized from
ethanol or 2-propanol.
4-Methyl-2-(3,5-dioxo-4-azatricyclo[5.2.1.02-endo,6-endo]-
dec-8-en-4-yl)pentanoic acid (Ve). Yield 85%, oily
substance, Rf 0.48 (ether). IR spectrum, cm–1: 3510, 1760,
1735, 1700, 1240, 740. Calculated, %: C 65.96; H 7.27;
N 4.81. C16H21NO4. Found, %: C 65.71; H 6.82; N 5.10.
3 - M e t h y l - 2 - ( 3 , 5 - d i o x o - 4 - a z a t r i c y c l o -
[5.2.1.02-endo,6-endo]-dec-8-en-4-yl)pentanoic acid (Vf).
Yield 87%, mp 101–102°C (water), Rf 0.60 (ether). IR
spectrum, cm–1: 3240, 3080, 1760, 1740, 1690, 1250, 725.
Calculated, %: C 65.96; H 7.27; N 4.81. C16H21NO4.
Found, %: C 65.77; H 7.12; N 5.05.
2-{9-(4-p-Nitrophenyl)-3,5-dioxo-4,9-diazatetra-
cyclo[5.3.1.02-endo,6-endo.08-exo,10-exo]-undec-4-yl}-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 2 2009

FEATURES OF REACTIONS BETWEEN (3,5-DIOXO-4-AZATRICYCLO-...
239
1610, 1525, 1350, 1275, 860. 1H NMR spectrum (300 MHz,
DMSO-d6), δ, ppm: 1.04 m (6H, 2CH3), 1.29 d (1H,
H11an), 1.71 d (1H, H11s), 1.89 m (2H, CH2), 2.44 m (1H,
H7), 2.60 m (1H, H1), 3.08 m (2H, H8, H10), 3.37 m (2H,
H2, H6), 4.44 m (1H, CH), 7.19 d (2Harom), 8.06 d
(2Harom), 12.93 br.s (1H, COOH). Calculated, %: C 61.82;
H 5.90; N 9.83. C22H25N3O6. Found, %: C 62.03; H 6.09;
N 9.90.
ethanoic acid (VIa). Yield 76%, mp 286–287°C
(acetone). IR spectrum, cm–1: 3360, 1760, 1730, 1700,
1
1590, 1505, 1335, 860. H NMR spectrum (500 MHz,
DMSO-d6), δ, ppm: 1.32 d (1H, H11an), 1.85 d (1H, H11s),
2.62 m (2H, H1, H7), 3.09 m (2H, H8, H10), 3.30 m (2H,
H2, H6), 3.99 d.d (2H, CH2COOH), 7.07 d (2Harom),
8.02 d (2Harom), 12.70 br.s (1H, COOH). Calculated, %:
C 57.14; H 4.20; N 11.76. C17H15N3O6. Found, %: C
56.35; H 4.11; N 11.38.
3-Methyl-2-{9-(4-p-nitrophenyl)-3,5-dioxo-4,9-
diazatetracyclo[5.3.1.02-endo,6-endo.08-exo,10-exo]undec-4-
yl}pentanoic acid (VIf). Yield 75%, mp 203–205°C
(2-propanol). IR spectrum, cm–1: 3390, 1760, 1730, 1700,
2-{9-(4-p-Nitrophenyl)-3,5-dioxo-4,9-diazatetra-
cyclo[5.3.1.02-endo,6-endo.08-exo,10-exo]undec-4-yl}pro-
panoic acid (VIb). Yield 72%, mp 281–282°C (2-pro-
panol). IR spectrum, cm–1: 3400, 1780, 1750, 1720, 1610,
1515, 1345, 865. 1H NMR spectrum (500 MHz, DMSO-d6),
δ, ppm: 1.30 d (1H, H11an), 1.42 d (3H, CH3), 1.82 d (1H,
H11s), 2.72 m (2H, H1, H7), 3.08 m (2H, H8, H10), 3.26 m
(1H, H6), 3.28 m (1H, H2), 4.54 q (1H, CHCOOH), 7.05
d (2Harom), 8.03 d (2Harom), 12.55 br.s (1H, COOH). Mass
spectrum, m/z (Irel, %) 371 (4) [M]+, 201 (100), 170 (15),
155 (28), 124 (12), 91 (15), 83 (23), 66 (42), 44 (15).
Calculated, %: C 58.22; H 4.58; N 11.32. C18H17N3O6.
Found, %: C 57.69; H 4.47; N 10.98.
1
1595, 1520, 1340. H NMR spectrum (300 MHz, CDCl3),
δ, ppm: 0.77 d (3H, CH3), 1.27 d (1H, H11an), 1.69 d (1H,
H11s), 1.89–1.99 m (2H, CH2), 2.43 m (1H, H7), 2.61 m
(1H, H1), 3.08 m (2H, H8, H10), 3.37 m (2H, H2, H6),
4.51 m (1H, CH), 7.18 d (2Harom), 8.05 d (2Harom), 13.03 s
(1H, COOH). Calculated, %: C 61.82; H 5.90; N 9.83.
C22H25N3O6. Found, %: C 61.93; H 5.88; N 9.80.
3-Phenyl-3-{9-(4-p-nitrophenyl)-3,5-dioxo-4,9-
diazatetracyclo[5.3.1.02-endo,6-endo.08-exo,10-exo]-undec-4-
yl}propanoic acid (VIg). Yield 70%, mp 169–171°C
(decomp.) (2-propanol). IR spectrum, cm–1: 3410, 3025,
1780, 1740, 1610, 1525, 1350, 1280, 860. 1H NMR spec-
trum (300 MHz, DMSO-d6), δ, ppm: 0.88 d (1H, H11an),
1.27 d (1H, H11s), 1.79–1.99 m (2H, CH2), 2.65 m (2H,
H1, H7), 2.82 m (2H, H8, H10), 3.14 m (2H, H2, H6),
4.24 t (1H, CH), 6.99 d (2Harom), 7.20–7.26 m (5H, HPh),
8.12 d (2Harom), 13.50 br.s (1H, COOH). Calculated, %:
C 64.42; H 4.73; N 9.39. C24H21N3O6. Found, %: C 64.20;
H 4.60; N 9.44.
3-{9-(4-p-Nitrophenyl)-3,5-dioxo-4,9-diazatetra-
cyclo[5.3.1.02-endo,6-endo.08-exo,10-exo]-undec-4-yl}pro-
panoic acid (VIc). Yield 66%, mp 190–191°C (2-pro-
panol). IR spectrum, cm–1: 3340, 1770, 1730, 1710, 1615,
1
1505, 1345, 860. H NMR spectrum (500 MHz,
DMSO-d6), δ, ppm: 1.18 d (1H, H11an), 1.70 d (1H, H11s),
2.36 m (2H, H1, H7), 2.98 m (2H, H8, H10), 3.20 m (2H,
CH2), 3.22 m (2H, H2, H6), 3.50 m (2H, CH2), 7.09 d
(2Harom), 8.04 d (2Harom), 12.18 s (1H, COOH). Cal-
culated, %: C 58.22; H 4.58; N 11.32. C18H17N3O6.
Found, %: C 57.81; H 4.39; N 11.09.
2-{9-(4-p-Nitrophenyl)-3,5-dioxo-4,9-diaza-tetra-
cyclo[5.3.1.02-endo,6-endo.08-exo,10-exo]undec-4-yl}-3-
methylsulfanylbutanoic acid (VIh). Yield 64%, mp
153–155°C (2-propanol). IR spectrum, cm–1: 3400, 1775,
1740, 1725, 1610, 1525, 1360, 860. 1H NMR spectrum
(300 MHz, DMSO-d6), δ, ppm: 1.28 d (1H, H11an),
1.70 d (1H, H11s), 1.91 s (3H, CH3), 2.17 m (2H, CH2),
2.37 m (2H, CH2), 2.45 m (1H, H7), 2.63 m (1H, H1),
3.07 m (2H, H8, H10), 3.34 m (2H, H2, H6), 4.64 t (1H,
CHCOOH), 7.17 d (2Harom), 8.05 d (2Harom), 12.95 br.s
(1H, COOH). Calculated, %: C 55.68; H 4.87; N 9.74.
C20H21N3O6S. Found, %: C 55.28; H 4.72; N 9.51.
6-{9-(4-p-Nitrophenyl)-3,5-dioxo-4,9-diazatetra-
cyclo[5.3.1.02-endo,6-endo.08-exo,10-exo]undec-4-yl}-
hexanoic acid (VId). Yield 61%, mp 130–131°C (2-pro-
panol). IR spectrum, cm–1: 3390, 1760, 1720, 1710, 1590,
1505, 1330, 855. 1H NMR spectrum (300 MHz, CDCl3),
δ, ppm: 1.08 m (4H, 2CH2), 1.26 d (1H, H11an), 1.25–
1.43 m (4H, 2CH2), 1.68 d (1H, H11s), 2.48 m (2H, H1,
H7), 3.05 m (2H, H8, H10), 3.27 m (2H, H2, H6), 3.29 d.d
(2H, CH2COOH), 7.18 d (2Harom), 8.05 d (2Harom),
11.99 s (1H, COOH). Calculated, %: C 61.02; H 5.57;
N 10.17. C21H23N3O6. Found, %: C 60.35; H 5.48; N 9.94.
2-{9-(4-p-Nitrophenyl)-3,5-dioxo-4,9-diazatetra-
cyclo[5.3.1.02-endo,6-endo.08-exo,10-exo]undec-4-yl}butan-
1,4-dioic acid (VIi). Yield 75%, mp 187–190°C (2-
propanol). IR spectrum, cm–1: 3355, 1770, 1740, 1710,
4-Methyl-2-{9-(4-p-nitrophenyl)-3,5-dioxo-4,9-
diazatetracyclo[5.3.1.02-endo,6-endo.08-exo,10-exo]-undec-4-
yl}pentanoic acid (VIe). Yield 73%, mp 195–197°C
(2-propanol). IR spectrum, cm–1: 3410, 1780, 1740, 1710,
1
1610, 1530, 1350, 870. H NMR spectrum (300 MHz,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 2 2009

TARABARA et al.
240
DMSO-d6), δ, ppm: 1.26 d (1H, H11an), 1.67 d (1H, H11s),
2.42–2.60 m (2H, CH2), 2.67 m (1H, H7), 2.93 m (1H,
H1), 3.04 m (2H, H8, H10), 3.31 m (2H, H2, H6), 4.85 d.d
(1H, CHCOOH), 7.12 d (2Harom), 8.03 d (2Harom), 12.95 br.s
(2H, 2COOH). Calculated, %: C 54.94; H 4.10; N 10.12.
C19H17N3O8. Found, %: C 54.51; H 3.81; N 9.86.
%: C 55.21; H 4.60; N 16.95. C19H19N5O6. Found, %:
C 55.15; H 4.47; N 16.87.
N-(Benzyl)-2-{5-(4-nitrophenyl)-9,11-dioxo-
3,4,5,10-tetraazatetracyclo[5.5.1.02-exo,6-exo.08-endo,12-
endo]-tridec-3-en-11-yl}ethaneamide (IXc). Yield 76%,
mp 176–177°C (decomp.) (ethanol). IR spectrum, cm–1:
1
3100, 3020, 1710, 1595, 1515, 1430, 1380, 1335, 855. H
2-{9-(4-p-Nitrophenyl)-3,5-dioxo-4,9-diazatetra-
cyclo[5.3.1.02-endo,6-endo.08-exo,10-exo]undec-4-yl}pentan-
1,5-dioic acid (VIj). Yield 70%, mp 188–189°C (2-pro-
NMR spectrum (500 MHz, DMSO-d6), δ, ppm: 1.23 d
(1H, H13an), 1.70 d (1H, H13s), 3.08 m (1H, H7), 3.20 m
(1H, H1), 3.48 m (2H, H8, H12), 4.03 d (1H, H6), 4.30 m
(2H, CH2), 4.88 d (1H, H2), 7.28 t (1H, NH), 7.33 d
(2Harom), 8.04 m (5H, HPh) 8.23 d (2Harom). Calculated,
%: C 60.76; H 4.64; N 17.72. C24H22N6O5. Found, %: C
61.02; H 4.50; N 17.49.
1
panol). H NMR spectrum (300 MHz, DMSO-d6), δ,
ppm: 1.25 d (1H, H11an), 1.65 d (1H, H11s), 1.94–2.26 m
(4H, 2CH2), 2.40 m (1H, H7), 2.59 m (1H, H1), 3.03 m
(2H, H8, H10), 3.32 m (2H, H2, H6), 4.78 d.d (1H,
CHCOOH), 7.13 d (2Harom), 8.02 d (2Harom), 12.79 br.s
(2H, 2COOH). Calculated, %: C 55.94; H 4.43; N 9.79.
C20H19N3O8. Found, %: C 55.75; H 4.37; N 9.58.
N-(4-Bromophenyl)-2-{5-(4-nitrophenyl)-9,11-
dioxo-3,4,5,10-tetraazatetracyclo[5.5.1.02-exo,6-exo.08-
endo,12-endo]tridec-3-en-11-yl}ethaneamide (IXd). Yield
89%, mp 213–215°C (decomp.) (ethanol). IR spectrum,
cm–1: 3380, 1690, 1590, 1540, 1520, 1425, 1335, 1250,
1080, 855. Calculated, %: C 51.21; H 3.53; N 15.58.
C23H19BrN6O5. Found, %: C 51.07; H 3.37; N 15.62.
Reactions of derivatives of 2-(3,5-dioxo-4-
azatricyclo[5.2.1.02-endo,6-endo]dec-8-en-4-yl}ethanoic
acid (Va) with p-nitrophenyl azide. General proce-
dure. A mixture of 0.003 mol of p-nitrophenyl azide and
0.003 mol of an appropriate ester VIIa, VIIb or amide
VIIIa–VIIIc in 10–15 ml of anhydrous chloroform was
boiled till the completion of the reaction (TLC monitoring).
The solvent was removed in a vacuum, to the residue 5–
7 ml of ether was added, the precipitate separated after
grinding was filtered off, washed with , ether on the filter,
dried in air, and recrystallized from 2-propanol.
N-[2-(1,3-Thiazolyl)]-2-{5-(4-nitrophenyl)-9,11-
dioxo-3,4,5,10-tetraazatetracyclo[5.5.1.02-exo,6-exo.08-
endo,12-endo]tridec-3-en-11-yl}ethaneamide (IXe). Yield
82%, mp 234–235°C decomp. (ethanol). IR spectrum,
cm–1: 3300, 1760, 1690, 1590, 1515, 1395, 1335, 1175,
860. Calculated, %: C 51.39; H 3.64; N 20.98.
C20H17N7O5S. Found, %: C 51.15; H 3.88; N 20.72.
(3,5-Dioxo-4-azatricyclo[5.2.1.02-exo,6-exo]-dec-8-
en-4-yl)ethanoic acid (XII).Amixture of 0.33 g (2 mmol)
of anhydride XI and 0.15 g (2 mmol) of aminoacetic acid
was boiled in 7–10 ml of glacial acetic acid. On completion
of the reaction (~8 h, TLC monitoring) the volatile
reaction products were removed in a vacuum, and 5 ml
of water was added to the residue. The precipitate was
filtered off, dried in air, and recrystallized from water.
Yield 78%, mp 120–122°C (149–150°C [10]). 1H NMR
spectrum (300 MHz, DMSO-d6), δ, ppm: 1.35 d (1H,
H10an), 1.62 d (1H, H10s), 2.76 m (2H, H1, H7), 3.13 m
(2H, H2, H6), 4.07 d (2H, CH2), 6.32 m (2H, H8, H9),
13.14 br.s (1H, COOH).
Methyl {5-(4-nitrophenyl)-9,11-dioxo-3,4,5,10-
tetraazatetracyclo[5.5.1.02-exo,6-exo.08-endo,12-endo]-
tridec-3-en-11-yl}ethanoate (IXa). Yield 93%, mp
206–208°C (ethanol). IR spectrum, cm–1: 3490, 1770,
1
1730, 1615, 1535, 1520, 1345, 1235, 855. H NMR
spectrum (300 MHz, DMSO-d6), δ, ppm: 1.12 d (1H,
H13an), 1.65 d (1H, H13s), 3.08 m (1H, H7), 3.19 m (1H,
H1), 3.49 m (2H, H8, H12), 3.66 s (3H, CH3), 3.92 d (1H,
H6), 4.28 m (2H, CH2COOCH3), 4.71 d (1H, H2), 8.30 d
(2Harom), 7.29 d (2Harom). Calculated, %: C 54.14; H 4.26;
N 17.54. C18H17N5O6. Found, %: C 53.95; H 4.07; N
17.32.
Ethyl {5-(4-nitrophenyl)-9,11-dioxo-3,4,5,10-
tetraazatetracyclo[5.5.1.02-exo,6-exo.08-endo,12-endo]-
tridec-3-en-11-yl}ethanoate (IXb).Yield 87%, mp 181–
182°C (ethanol). IR spectrum, cm–1: 1770, 1740, 1710,
2-{9-(4-Nitrophenyl)-3,5-dioxo-4,9-diazatetra-
cyclo[5.3.1.02-exo,6-exo.08-exo,10-exo]undec-4-yl}ethanoic
acid (XIII). A mixture of 0.22 g (1 mmol) of acid XII
and 0.25 g (1.5 mmol) of p-nitrophenyl azide in 10 ml of
chloroform was boiled till the completion of the reaction
(TLC monitoring). The precipitate separated on cooling
was filtered off, washed with chloroform on the filter,
1
1680, 1595, 1520, 1510, 1340, 1245, 855. H NMR
spectrum (300 MHz, DMSO-d6), δ, ppm: 1.12 t (3H, CH3),
1.14 d (1H, H13an), 1.68 d (1H, H13s), 3.10 m (1H, H7),
3.20 m (1H, H1), 3.50 m (2H, H8, H12), 3.93 d (1H, H6),
4.11 q (2H, CH2), 4.26 m (2H, CH2COOEt), 4.77 d (1H,
H2, 3J2,6 9.0), 7.32 d (2Harom), 8.33 d (2Harom). Calculated,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 2 2009

FEATURES OF REACTIONS BETWEEN (3,5-DIOXO-4-AZATRICYCLO-...
241
dried in air, and recrystallized from acetone. Yield 67%,
mp 186–188°C (decomp.) (2-propanol). IR spectrum,
cm–1: 3410, 3030, 1760, 1725, 1610, 1520, 1345, 1285,
Konovalov,A.I., Zh. Org. Khim., 1981, vol. 17, p. 1626.
6. Zalkow, L.H. and Oehlschlager,A.C., J. Org. Chem., 1963,
vol. 28, p. 3303; Kozlowska-Gramsz, E., Pol. J. Chem., 1985,
vol. 59, p. 493; Hermes, M.E. and Marsh, F.D., J. Org. Chem.,
1972, vol. 37, p. 2969; Da Silva,A.E., Nunes, R.J., and Uiea-
ra, M., Synth. Commun., 2004, vol. 34, p. 3073.
7. Zalkow, L.H. and Kennedy, C.D., J. Org. Chem., 1963,
vol. 28, p. 3309; Oehlschlager, A.C. and Zalkow, L.H.,
Canad. J. Chem., 1969, vol. 47, p. 461.
8. Tarabara, I.N., Kas’yan, A.O., Yarovoi, M.Yu., Shishki-
na, S.V., Shishkin, O.V., and Kas’yan, L.I., Zh. Org. Khim.,
2004, vol. 40, p. 1033; Kas’yan, L.I., Tarabara, I.N., Kas’-
yan, A.O., and Yarovoi, M.Yu., Zh. Org. Khim., 2003,
vol. 39, p. 1698.
9. Koch, H. and Kotlan, J., Monatsh. Chem., 1966, vol. 97,
p. 1648; Koch, H., Kotlan, J., and Braun, H., Monatsh.
Chem., 1967, vol. 98, p. 702; Koch, H., Kotlan, J., Far-
kouh, E., and Linder, M., Monatsh. Chem., 1971, vol. 102,
p. 609.
10. Biagini, S.C.G., Bush, S.M., Gibson, V.C., Mazzarioi, L.,
North, M., Teasdale, W.G., Williams, C.M., Zagotto, G., and
Zamuner, D., Tetrahedron, 1995, vol. 51, p. 7242.
11. Jones, I.A., Jones, W., and North, M., Tetrahedron, 1999,
vol. 55, 279; Hibbs, D.E., Hursthouse, M.B., Jones, I.G.,
Jones, W., Malik, K.M.A., and North, M., J. Org. Chem.,
1998, vol. 63, p. 1496; Jones, I.A., Jones, W., and North, M.,
J. Org. Chem., 1998, vol. 63, p. 1505; Ranga-Nathan, D.,
Haridas, V., Kurur, S., Nagaraj, R., Bikshapathy, E., Kun-
war,A.C., Sarma,A.V.S., and Vairamani, M., J. Org. Chem.,
2000, vol. 65, p. 365.
1
860. H NMR spectrum (300 MHz, CDCl3), δ, ppm:
0.88 d (1H, H11an), 1.65 d (1H, H11s), 2.65 m (2H, H1,
H7), 2.83 m (2H, H2, H6), 3.10 m (2H, H8, H10), 4.25 d
(2H, CH2), 6.99 d (2Harom), 8.12 d (2Harom), 12.80 s (1H,
COOH). Calculated, %: C 57.14; H 4.20; N 11.76.
C17H15N3O6. Found, %: C 57.07; H 4.17; N 11.55.
Ethyl-2-{9-(4-nitrophenyl)-3,5-dioxo-4,9-diaza-
tetracyclo[5.3.1.02-endo,6-endo.08-exo,10-exo]-undec-4-
yl}ethanoate (XIV). Amixture of 0.50 g (2 mmol) of ester
VIIb, 0.44 g (2 mmol) of acid Va, and 0.82 g (5 mmol) of
p-nitrophenyl azide in 15 ml of chloroform was boiled till
the completion of the reaction (TLC monitoring). The
precipitate of aziridine VIa separated on cooling was
filtered off, washed with chloroform on the filter, the
organic layer was twice washed with a saturated solution
of sodium hydrogen carbonate and dried with calcined
magnesium sulfate. The solvent was removed in a vacu-
um, the residue was recrystallized from 2-propanol. Yield
71%, mp 158–160°C (2-propanol). IR spectrum, cm–1:
1785, 1760, 1725, 1610, 1520, 1345, 1270, 860. 1H NMR
spectrum (300 MHz, DMSO-d6), δ, ppm: 0.91 t (3H, CH3),
1.27 d (1H, H11an), 1.67 d (1H, H11s), 2.52 m (2H, H1,
H7), 3.06 m (2H, H8, H10), 3.33 m (2H, H2, H6), 3.86 q
(2H, CH2), 4.10 s (2H, CH2), 7.17 d (2Harom), 8.04 d
(2Harom). Calculated, %: C 59.22; H 4.93; N 10.91.
C19H195N3O6. Found, %: C 59.17; H 5.03; N 11.07.
12. Tarabara, I.N., Yarovoi, M.Yu., Isaev, A.K., and Kas’-
yan, L.I. V³snik DNU. Kh³m., 2002, no. 8, p. 36;Tarabara, I.N.,
Yarovoi, M.Yu., Bondarenko, Ya.S., and Kas’yan, L.I.,
V³snik DNU. Kh³m., 2003, no. 9, p. 35; Tarabara, I.N.,
Bondarenko, Ya.S., and Kas’yan, L.I., Vopr. Khim. &Khim.
Tekhnol., 2004, no. 3, p. 45.
The study was carried out under the financial support
of the State Ukrainian Foundation for Basic Research
(project F25.3/067).
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