Reactions of 4-amino-4-azatricyclo[5.2.1.02,6-endo ]dec-8-ene-3,5-dione with dicarboxylic acid anhydrides

Article abstract of DOI:10.1134/S1070428007070135

Reactions of 4-amino-4-azatricyclo[5.2.1.0^2,6-endo ]dec-8-ene-3,5-dione (hydrazinolysis product of endic anhydride) with succinic, maleic, cis-cyclohexane-1,2-dicarboxylic, endic, phthalic, and 1,8-naphthalic anhydrides were studied. Procedures

Full text of DOI:10.1134/S1070428007070135

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2007, Vol. 43, No. 7, pp. 1014–1026. © Pleiades Publishing, Ltd., 2007.
Original Russian Text © L.I. Kas’yan, I.N. Tarabara, Ya.S. Bondarenko, L.K. Svyatenko, A.V. Bondarenko, 2007, published in Zhurnal Organicheskoi
Khimii, 2007, Vol. 43, No. 7, pp. 1020–1032.
Reactions of 4-Amino-4-azatricyclo[5.2.1.02,6-endo]dec-8-ene-
3,5-dione with Dicarboxylic Acid Anhydrides
L. I. Kas’yan, I. N. Tarabara, Ya. S. Bondarenko, L. K. Svyatenko, and A. V. Bondarenko
Dnepropetrovsk National University, per. Nauchnyi 13, Dnepropetrovsk, 49050 Ukraine
Received September 28, 2006
Abstract—Reactions of 4-amino-4-azatricyclo[5.2.1.02,6-endo]dec-8-ene-3,5-dione (hydrazinolysis product of
endic anhydride) with succinic, maleic, cis-cyclohexane-1,2-dicarboxylic, endic, phthalic, and 1,8-naphthalic
anhydrides were studied. Procedures for the preparation of the corresponding hydrazido acids and bis-imides
were proposed. Their reactions with peroxyformic acid, depending on the substrate nature, led to the formation
of both epoxy hydrazido acids and epoxy imides. The unsaturated adducts reacted with p-nitrophenyl azide to
give the corresponding triazole derivatives.
DOI: 10.1134/S1070428007070135
Organic hydrazine derivatives have found wide
application in medicine as compounds exhibiting anti-
tuberculous, anticancer, psychotherapeutic, and other
kinds of biological activity [1]. Some dicarboxylic acid
hydrazides, in particular those derived from succinic,
maleic, and phthalic acids, were found to possess
bacteriostatic, antiphlogistic, analgetic, anticonvulsant,
antiarrhythmic, hypertensive, and antiviral activity [2].
Compounds of this group are also characterized by
pronounced antiaggregation effect [3] and hepatopro-
tective properties [4], and they induce liver cyto-
chrome P-450 system [5].
pound II with dicarboxylic acid anhydrides were
almost not studied previously; therefore, the goal of
the present study was to fill up this gap.
As reagents we used succinic, maleic, cis-cyclo-
hexane-1,2-dicarboxylic, endic, phthalic, and 1,8-naph-
thalic anhydrides IIIa–IIIf.
O
O
O
O
O
O
O
O
O
IIIa
IIIb
IIIc
Products of hydrazine reactions with alicyclic acids,
specifically with bicyclo[2.2.1]hept-5-ene-endo-2,-
endo-3-dicarboxylic (endic) acid, have been studied to
a lesser extent. We previously [6] demonstrated that
hydrazide II obtained by condensation of endic anhy-
dride (I) with hydrazine hydrate can be converted into
various organic compounds via reactions with a num-
ber of electrophilic reagents, such as arenesulfonyl
chlorides, benzoyl chlorides, aromatic isocyanates, iso-
thiocyanates, and oxiranes. The structure of hydrazide
II was proved by the X-ray diffraction data [6], which
ruled out alternative structure IIa. Reactions of com-
O
O
O
O
O
O
O
O
O
IIId
IIIe
IIIf
Reactions of hydrazide II with dicarboxylic acid
anhydrides were carried out in anhydrous benzene,
ethyl acetate, and chloroform. Following one of the
procedures proposed for reactions of endic anhydride
with various amines [7], we succeeded in obtaining
hydrazido acids IVd and IVe in 80 and 76% yield,
respectively (Scheme 1). The second procedure [8]
implies reaction of equimolar amounts of hydrazide II
and the corresponding anhydride on heating for a short
time in ethyl acetate; here, the yields of IVa, IVb, and
IVe were 53, 88, and 78%, respectively. The maximal
O
O
O
NH
NH
O
N
NH2
O
O
O
I
II
IIa
1014

REACTIONS OF 4-AMINO-4-AZATRICYCLO[5.2.1.02,6-endo]DEC-8-ENE-3,5-DIONE
1015
Scheme 1.
O
O
O
COOH
1
10
7
3
5
2
6
X
X
9
8
N
NH2
+
O
O
4 N NH
O
O
O
II
IIIa–IIIe
IVa–IVe
X = CH2CH2 (a), cis-CH=CH (b),
(c),
(d),
(e).
yields of IVa–IVe were obtained in the reactions of
equimolar amounts of hydrazide II and anhydrides III
in anhydrous chloroform. The reactions in benzene
required the longest time (TLC), while the products
formed in ethyl acetate required additional purifica-
tion. The use of chloroform as solvent ensured con-
siderably shorter reaction time and easier isolation
procedure (unreacted initial compounds are removed
by washing the product with the solvent).
ular symmetry, protons on C8/C9, C1/C7, and C2/C6 in
the bicycloheptane skeleton resonated at δ 6.06/6.07,
3.44/3.46, and 3.28/3.35 ppm, respectively; the syn-
and anti-10-H protons of the methylene bridge gave
a single signal at δ 1.55 (IVb) and 1.56 ppm (IVe).
Signals from protons in the exocyclic olefinic fragment
in molecule IVb appeared at δ 6.48 and 6.14 ppm.
The OH and NH signals were located at 10.79 and
10.90 ppm (IVb) and 6.25 and 7.72 ppm (IVe),
respectively.
However, none of the above procedures turned out
to be suitable for the synthesis of acid IVf from
1,8-naphthalic anhydride (IIIf). A probable reason is
poor solubility of the reagent in the solvents used.
Therefore, the reaction of IIIf with hydrazide II was
carried out in acetonitrile, but the yield of target prod-
uct IVf was only 12% (Scheme 2).
1
The H NMR spectrum of compound IVd is more
complex. Apart from signals belonging to the carboxy
(OH, δ 11.52 ppm) and amide groups (NH, 6.10 ppm),
the spectrum contained signals from protons in both
bicycloheptene fragments, which appeared separately
due to asymmetric structure of one of these fragments
(amido acid). The 1-H and 7-H protons (δ 3.56 and
3.59 ppm), as well as protons of the methylene bridge
(syn-10-H and anti-10-H; δ 1.58 and 1.53 ppm, respec-
Scheme 2.
O
O
O
O
2
tively, J = 8.7 Hz) in the imide fragment were non-
equivalent. The other bicycloheptene fragment in mol-
ecule IVd was characterized by the following signals,
δ, ppm: 6.22 (5′-H), 5.82 (6′-H), 3.29 (1′-H), 3.06
(4′-H), 3.10 (2′-H), 2.92 (3′-H), 1.31 and 1.22 (7-H,
2J = 8.1 Hz).
N
NH2 +
O
IIIf
II
O
O
O
5'
4'
O
O
MeCN
1
3
N
NH
6'
2
7'
9
8
3'
4
HOCO
10
N
5
NH
HO
2'
1'
6
7
IVf
O
O
IVd
The IR spectra of acids IVa–IVf contained absorp-
tion bands due to imide carbonyl groups in the regions
1807–1760 and 1755–1735 cm–1. The amide groups
gave rise to absorption bands at 3320–3210, 1685–1625
(amide I), 1550–1525 (amide II), and 1270–1215 cm–1
(amide III), respectively [9]. The H NMR spectra of
compounds IVb and IVe were more informative from
Using thin-layer chromatography, we compared on
a qualitative level the reactivity of anhydrides IIIa–
IIIe toward 4-amino-4-azatricyclo[5.2.1.02,6-endo]dec-8-
ene-3,5-dione (II) in chloroform. Samples of the reac-
tion mixtures were withdrawn in increasing intervals
(2, 5, 10, 30, and 60 min), and the plates were eluted
with propan-2-ol–diethyl ether (1:10). The reaction
1
the viewpoint of structure assignment. Due to molec-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 7 2007

KAS’YAN et al.
1016
Scheme 3.
O
O
O
O
O
COOH
X
AcOH, reflux
IIIa–IIIf, AcOH, reflux
N
NH
N
N
X
N
NH2
O
O
O
O
IVa–IVf
Va–Vf
II
X = CH2CH2 (a), cis-CH=CH (b),
(c),
(d),
(e),
(f).
time increased in the series: IVb < IVd ≈ IVc < IVe <
IVa; it was 10 h, 20 min, and 6 h in the synthesis of
compounds IVa, IVb, and IVd, respectively.
bands in the region 1820–1710 cm–1 [9]. Unlike amido
acids IV, the H NMR spectra of bis-imides Vb–Ve
lacked signals assignable to carboxy and amide groups
(OH, NH); in addition, the 1-H and 7-H signals ap-
peared in a weaker field (Δδ = 0.22–0.28 ppm).
The presence of a strained double C=C bond in
molecules of compounds IV and V makes them prom-
ising as subjects for studying their further transforma-
tions with participation of the unsaturated fragment. In
particular, it was interesting to examine their reactions
with peroxy acids and azides. It is known that many
epoxy derivatives exhibit a broad spectrum of bio-
logical activity [13], and development of optimal
procedures for their preparation is related to estimation
of structural specificity of substrates and oxidant
properties [14].
1
Amido acids IVa–IVf were then converted into the
corresponding bis-imides Va–Vf by heating in boiling
glacial acetic acid (Scheme 3). Compounds Va–Vf
were also synthesized directly from hydrazide II and
the corresponding anhydride under analogous condi-
tions. Bis-imides Va and Vb were obtained previously
[10] just following the latter procedure. Hedaya and
Hinmann [11] reported on successful preparation of
imide Vd by heating 2 equiv of endic anhydride with
hydrazine hydrate in alcohol. Bis-imides Vc and Vd
were also isolated on attempted recrystallization of
compounds IVc and IVd from propan-2-ol. Sample of
bis-imides prepared by different procedures had iden-
tical melting points and IR spectra which contained
absorption bands corresponding to the strained norbor-
nene fragment at 3090–3075 (ν=C–H) and 745–715 cm–1
(δ=C–H) [12], as well as imide carbonyl absorption
Bis-imides Va–Vc, Ve, and Vf were subjected to
oxidation with peroxyformic acid which was previ-
ously shown to act as an effective epoxidizing agent
toward cage-like imides [15]. Peroxyformic acid was
Scheme 4.
O
O
O
O
1
11
7
3
5
2
6
10
8
HCO3H, 30–35°C
9
O
N
N
X
4 N
N
X
O
O
O
O
Va–Vc, Ve, Vf
VIa–VIe
(d),
VI, X = CH2CH2 (a), cis-CH=CH (b),
(c),
(e).
O
O
O
O
O
O
HCO3H
30–35°C
4HCO3H
30–35°C
O
N
N
N
N
O
N
N
O
O
O
O
O
O
O
VIf
Vd
VIg
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 7 2007

REACTIONS OF 4-AMINO-4-AZATRICYCLO[5.2.1.02,6-endo]DEC-8-ENE-3,5-DIONE
1017
Calculated and experimental chemical shifts of protons in the bicyclic fragments of compounds Vd and VІf
O
O
O
O
1
10
7
7'
10'
1'
1
11
7
7'
10'
1'
3
5
3
5'
5'
2
6
2
6
6'
6'
10
8
8'
9'
8'
9'
9
8
9
O
4N N 4'
4 N N 4'
2'
2'
3'
3'
5
O
O
O
O
Vd
VIf
Calculated chemical shifts δ, ppm
Experimental chemical shifts δ, ppm
Proton
Vd
VІf
Vd
VІf
1-H
2-H
6-H
7-H
8-H
3.36
3.14
3.11
3.34
6.96
6.99
1.86
1.45
3.36
3.14
3.11
3.34
6.96
6.99
1.86
1.45
2.98
3.00
2.97
2.96
3.35
3.32
1.94
0.93
3.38
3.17
3.20
3.40
7.03
7.02
1.89
1.49
3.56
3.27
3.27
3.55
6.04
6.04
1.56
1.51
3.56
3.27
3.27
3.55
6.04
6.04
1.56
1.51
3.57
2.95
2.95
3.52
3.16
3.10
1.38
1.06
3.57
3.29
3.29
3.52
6.08
6.08
1.55
1.51
9-H (10-H)
syn-10-H (syn-11-H)
anti-10-H (anti-11-H)
1′
2′
6′
7′
8′
9′
syn-10′-H
anti-10′-H
generated in situ from 98% formic acid and 50%
hydrogen peroxide; no other solvent was added, and
the reactions were carried out at 30–35°C under TLC
control. In most cases, the reaction was complete in 2–
4 h, and the only products were the corresponding ep-
oxy bis-imides VIa–VIe (Scheme 4). Using different
oxidant-to-substrate molar ratios in the reaction with
bis-imide Vd having two equivalent strained double
bonds we succeeded in isolating both mono- and di-
epoxy derivatives VIf and VIg.
The structure of epoxy derivatives was confirmed
by IR and H NMR spectroscopy. Compounds VIa–
1
VIg displayed in the IR spectra absorption bands typ-
ical of the imide fragments and bands at 865–855 cm–1
due to stretching vibrations of oxirane C–O bonds
[13]. The 1H NMR spectra of epoxides VIb, VId, VIf,
and VIg, in contrast to their unsaturated precursors,
contained signals at δ 3.12–3.20 ppm from protons in
the three-membered ring, and the anti-11-H signal was
displaced upfield (δ 1.01–1.12 ppm) due to magnet-
ically anisotropic effect of the oxirane ring.
The oxidation of bis-imide Vb in which the double
bonds are nonequivalent gave the corresponding mono
epoxy derivative VІb only at the strained double bond
in the bicycloheptene fragment, while the double bond
in the maleimide moiety remained intact. The latter
failed to undergo epoxidation with hydrogen peroxide
in alkaline medium [16]. In the reaction of bis-imide
Vb with equimolar amounts of potassium hydroxide
and 50% hydrogen peroxide in alcohol, only hydrol-
ysis products of imide Vb were isolated instead of
oxidation products.
We calculated the chemical shifts of protons in
molecules Vd and VIf for the gas phase in terms of
the Hartree–Fock theory using the continuous set of
gauge transformations method and standard 6-311++G
(3d,2p) basis set [HF/CSGT/6-311++G(3d,2p)] [17].
The structures were optimized by the MP2/6-311G*
method. The calculated values together with the ex-
perimental chemical shifts are given in table. The re-
sults of calculations strongly facilitated signal assign-
1
ment in the H NMR spectra and showed equivalence
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 7 2007

KAS’YAN et al.
1018
Scheme 5.
O
O
O
O
OH
O
OH
O
HCO3H, 30–35°C
N
NH
O
N
NH
O
O
+
IVa
VII
O
O
N
O
O
N
O
O
HCO3H, 30–35°C
N
NH
HO
N
O
N
O
O
O
O
O
O
O
IVe
Ve
VId
O
O
O
O
O
HCO3H, 30–35°C
+
N
NH
HO
N
N
O
N
N
O
O
O
O
O
O
IVd
Vd
VIe
O
O
+
O
N
N
O
O
O
VIg
of protons in both cage-like fragments in molecule Vd.
The chemical shifts of protons in molecule Vd de-
crease in the following series: 8-H, 9-H > 1-H, 7-H >
2-H, 6-H > syn-10-H > anti-10-H. The same series is
retained for the unsaturated bicycloheptene fragment in
monoepoxide VІf, while resonance of protons in the
epoxy fragment is characterized by the series 8-H,
10-H > 1-H, 7-H ≈ 2-H, 6-H > syn-11-H > anti-11-H.
reactant ratio on the composition of oxidation prod-
ucts. At an equimolar reactant ratio, the products were
compounds Vd, VIf, and VIg at a ratio of 1.0:4.0:
0.25. In the reaction of IVd with 4 equiv of HCO3H
we obtained bis-epoxy derivative VIg as the major
product (72%), and the yields of compounds Vd and
VIf were 2 and 8%, respectively (1H NMR data).
We presumed that formic acid acts as dehydrating
agent facilitating closure of imide ring and that the
imides thus formed are oxidized with peroxyformic
acid to the corresponding epoxy derivatives. In fact,
when a mixture of acid IVe and 98% formic acid was
stirred for 2 days in the absence of hydrogen peroxide,
23.2% of bis-imide Ve was formed. Heating of that
mixture at 70–80°C resulted in almost complete trans-
formation of IVe into bis-imide Ve.
The oxidation of hydrazide II with peroxyformic
acid was accompanied by tarring, presumably due to
the presence in molecule II of a primary amino group
which is known to readily undergo oxidation and sub-
sequent decomposition. Our attempt to effect epoxida-
tion of compound II in the presence of p-toluenesul-
fonic acid (i.e., of the corresponding ammonium salt)
was also unsuccessful. Therefore, we synthesized
1
As follows from the H NMR data, molecule of bis-
epoxide VІg is symmetric (like initial bis-imide Vd).
We also tried to oxidize hydrazido acids IVa and
IVe with peroxyformic acid. From compound IVa we
obtained epoxide VII (Scheme 5) whose structure was
1
confirmed by the IR and H NMR data. The oxidation
of IVe with 2 equiv of peroxyformic acid (reaction
time 24 h) gave imide Ve and its epoxy derivative VId;
also, the initial compound was partially recovered from
the reaction mixture, the ratio IVe:Ve :VId being
1
1.0:2.2:8.0 according to the H NMR data. Under
analogous conditions, the reaction with hydrazido acid
IVd resulted in the formation of bis-imide Vd, its
monoepoxy derivative VIf, and bis-epoxide VIg at
a ratio of 1:10:40 (1H NMR data). Using compound
IVd as an example, we examined the effect of the
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REACTIONS OF 4-AMINO-4-AZATRICYCLO[5.2.1.02,6-endo]DEC-8-ENE-3,5-DIONE
1019
Scheme 6.
O
O
O
O
O
N2H4 · H2O
i-PrOH, reflux
N2H4 ·H2O
i-PrOH, reflux
O
N
N
O
N
NH2
O
N
N
O
O
O
O
O
O
VIg
VId
VIII
epoxy derivative of II by an indirect method. For
this purpose, epoxy bis-imide VId was treated with
1.5 equiv of 80% aqueous hydrazine hydrate in boiling
isopropyl alcohol. The yield of epoxy hydrazide VІІІ
was 43% (Scheme 6). Better results were obtained
using symmetric bis-epoxide VIg as initial compound;
in this case, the yield of VIII was 67%, and the prod-
uct was purer. Compound VIII showed in the IR spec-
trum absorption bands due to stretching vibrations of
the imide carbonyl groups (1780–1690 cm–1), N–H
bonds in the primary amino group (3335 and 3280 cm–1
[9]), and oxirane C–O bonds (a strong band at 865 cm–1
p-nitrophenyl azide. Both hydrazido acid IVe and bis-
imides Va, Vc, Ve, and Vf were brought into reaction
with p-nitrophenyl azide in boiling chloroform. As a re-
sult, the corresponding dihydro-1,2,3-triazole deriva-
tives ІX and Xa–Xd were isolated (Scheme 7).
Insofar as bis-imide Vd is poorly soluble in chloro-
form, its reaction with p-nitrophenyl azide was carried
out in boiling isopropyl alcohol. Depending on the
reactant ratio, mono- and bis-triazolo derivatives Xe
and Xf were obtained (Scheme 8).
The double C=C bonds in molecule Vb are non-
equivalent. It is known [19] that the double bond in
maleimide derivatives is also capable of reacting with
aromatic azides according to the [3+2]-cycloaddition
pattern. In the reaction of equimolar amounts of p-ni-
trophenylazide and bis-imide Vb in chloroform we
isolated dihydrotriazole derivative Xg as the only
product (Scheme 9); these data indicate higher reac-
1
[12]). Protons on C8 and C10 appeared in the H NMR
spectrum of VIII at δ 2.98 ppm, i.e., in the region
typical of most epoxynorbornanes [18], and the amino
group gave rise to a signal at δ 4.91 ppm.
We also examined the behavior of unsaturated
cage-like imides in dipolar [3+2]-cycloaddition to
Scheme 7.
O
O
O
O
4-O2NC6H4N3
CHCl3, reflux
N
N
N
NH
HO
N
N
NH
HO
O
O
O
O
O2N
IVe
IX
O
O
O
O
O
1
13
7
3N
4-O2NC6H4N3
CHCl3, reflux
11
2
6
12
N
N
X
4N
10 N
O
N
X
8
N
9
5
O
O
O2N
Va, Vc, Ve, Vf
Xa–Xd
X, X = CH2CH2 (a),
(b),
(c),
(d).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 7 2007

KAS’YAN et al.
1020
Scheme 8.
O
O
N
N
N
N
N
1:1
O
O
O
O
4-O2NC6H4N3
i-PrOH, reflux
NO2
Xe
N
N
O
O
O
O
N
N
N
Vd
N
N
N
N
1:3
N
O
O
O2N
NO2
Xf
tivity of the strained C=C bond in the norbronene frag-
ment. In the presence of 3 equiv of p-nitrophenylazide,
the product was bis-triazole Xh resulting from azide
addition at both unsaturated fragments in molecle Vb.
Davis and Rondestvedt [20] showed that addition of
azides to maleimides could produce both dihydrotri-
azole and aziridine derivatives, depending on the sol-
vent. However, in the reaction of epoxy bis-imide VIb
with p-nitrophenyl azide in boiling isopropyl alcohol
we isolated only triazole derivative XІ (Scheme 10).
In the IR spectra of compounds IX–XI we ob-
served absorption bands arising from vibrations of
the skeletal bonds, nitro group (1530–1515, 1350–
1325 cm–1), and N=N and aromatic C=C bonds (1610–
1600 cm–1) [9, 21]. Insofar as compounds ІX, Xc,
Xe–Xh, and XІ contain unsymmetrically substituted
1
dihydrotriazole fragments, their H NMR spectra
differ from the spectra of the corresponding epoxy
derivatives and show considerable nonequivalence of
protons in the tetracyclic skeleton (2-H/6-H, 1-H/7-H,
Scheme 9.
O
O
N
N
N
N
N
1:1
O
O
O
O
4-O2NC6H4N3
CHCl3, reflux
O2N
N
Xg
N
N
O
O
O
O
N
N
Vb
N
N
N
N
1:3
N
O
O
O2N
NO2
Xh
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 7 2007

REACTIONS OF 4-AMINO-4-AZATRICYCLO[5.2.1.02,6-endo]DEC-8-ENE-3,5-DIONE
1021
Scheme 10.
O
O
O
O
4-O2NC6H4N3
i-PrOH, reflux
N
N
O
N
N
O
N
N
N
O
O
O
O
NO2
VIb
XI
8-H/12-H). The largest difference in chemical shifts is
observed for the 2-H and 6-H protons which resonate
at δ 4.76–4.99 and 3.88–4.12 ppm, respectively (3J =
8.7–9.4 Hz) [21, 22]. In the spectra of ІX, Xc, and
Xe–Xh, signal from one proton of the methylene
bridge (syn-13-H) is slightly displaced downfield
(δ 1.66–1.76 ppm) relative to the corresponding signal
in the spectra of initial imides (δ 1.56–1.63 ppm),
while the anti-13-H proton resonates in a stronger field
(δ 1.14–1.34 ppm).
anhydride in 10 ml of ethyl acetate was heated until it
became homogeneous. The mixture was left to stand
until the reaction was complete (TLC), the solvent was
removed under reduced pressure, and the residue was
purified by recrystallization. In such a way, com-
pounds IVa and IVe were obtained.
c. Compound II, 3.56 g (20 mmol), was dissolved
in 10 ml of chloroform, 20 mmol of the corresponding
dicarboxylic acid anhydride was added under stirring,
and the mixture was stirred until the reaction was com-
plete (TLC). The precipitate was filtered off, washed
with chloroform on a filter, dried in air, and subjected
to additional treatment. Following this procedure, com-
pounds IVa–IVe were obtained.
EXPERIMENTAL
The IR spectra were measured in KBr on UR-20
1
and Paragon 500 FT-IR spectrometers. The H NMR
4-[(1R,2R,6S,7R)-(3,5-Dioxo-4-azatricyclo-
[5.2.1.02,6]dec-8-en-4-ylamino]-4-oxobutanoic acid
(IVa). Yield 53 (b), 74% (c), mp 185–186°C (from
propan-2-ol), Rf 0.58. IR spectrum, ν, cm–1: 3250,
3215, 1790, 1740, 1720, 1625, 1530, 1250, 745. Found,
%: N 10.10. C13H14N2O5. Calculated, %: N 10.07.
spectra were recorded on Varian VXR-300 (300 MHz)
and Varian Unity (200 MHz) spectrometers from solu-
tions in DMSO-d6 using HMDS or TMS as internal
reference. The progress of reactions and the purity of
products were monitored by TLC on Silufol UV-254
plates (eluent isopropyl alcohol; development with
iodine vapor). The elemental compositions were deter-
mined on a Carlo Erba analyzer.
4-Amino-4-azatricyclo[5.2.1.02, 6-endo]dec-8-ene-3,5-
dione (II) was prepared by reaction of 10.3 g
(0.062 mol) of endic anhydride (I) with 6.1 ml
(0.062 mol) of 80% aqueous hydrazine hydrate accord-
ing to the procedure described in [23]. Yield 91.4%,
mp 146–147°C; published data [23]: mp 145–146°C.
(Z)-4-[(1R,2R,6S,7R)-(3,5-Dioxo-4-azatricyclo-
[5.2.1.02,6]dec-8-en-4-ylamino]-4-oxobut-2-enoic
(IVb). Yield 88 (b) (oily substance), 76% (c), mp 128–
130°C, Rf 0.69. IR spectrum, ν, cm–1: 3515, 3320,
3080, 1807, 1755, 1715, 1665, 1530, 1255, 740, 725.
1H NMR spectrum, δ, ppm: 10.79 s (1H, COOH),
3
6.48 d (1H, HC=, J = 12.2 Hz), 6.25 s (1H, NH),
6.14 d (HC=), 6.06 m (2H, 8-H, 9-H), 3.44 m (2H,
1-H, 7-H), 3.28 m (2H, 2-H, 6-H), 1.55 d (2H, syn-
10-H, anti-10-H). Found, %: H 10.25. C13H12N2O5.
Calculated, %: N 10.14.
Imidocarbamoylcarboxylic acids IVa–IVe (gen-
eral procedure). a. A mixture of 3.56 g (20 mmol) of
compound II and 20 mmol of the corresponding dicar-
boxylic acid anhydride in 10 ml of benzene was stirred
until the reaction was complete (TLC). The precipitate
was filtered off, washed with benzene on a filter,
dried in air, and subjected to additional treatment.
This procedure was used to synthesize compounds
IVd and IVe.
(1S,2R)-2-[(1R,2R,6S,7R)-(3,5-Dioxo-4-azatricy-
clo[5.2.1.02,6]dec-8-en-4-ylcarbamoyl]cyclohexane-
carboxylic acid (IVc). Yield 69% (c), mp 159–160°C,
Rf 0.82. IR spectrum, ν, cm–1: 3340, 3220, 3085, 1760,
1740, 1715, 1660, 1535, 1270, 740. Found, %: N 8.27.
C17H20N2O5. Calculated, %: N 8.43.
b. A mixture of 3.56 g (20 mmol) of compound II
and 20 mmol of the corresponding dicarboxylic acid
(1S,2S,3R,4S)-3-[(1R,2R,6S,7R)-(3,5-Dioxo-4-aza-
tricyclo[5.2.1.02,6]dec-8-en-4-ylcarbamoyl]bicyclo-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 7 2007

KAS’YAN et al.
1022
[2.2.1]hept-5-ene-2-carboxylic acid (IVd). Yield 80
(a), 94% (c), mp 179–180°C (decomp.), Rf 0.46. IR
spectrum, ν, cm–1: 3510, 3210, 3085, 1800, 1745,
c. A solution of 20 mmol of compound IVc or IVd
in 15–20 ml of ethanol was heated for 5–7 min under
reflux and was then allowed to slowly cool down. The
precipitate of bis-imide Vc or Vd was filtered off,
washed on a filter with 3–5 ml of ethanol, and dried in
air. Compounds Vc or Vd obtained in such a way
required no additional purification.
1
1725, 1650, 1550, 1215, 730. H NMR spectrum, δ,
3
ppm: 11.52 s (1H, COOH), 6.22 d.d (1H, 5′-H, J5′,6′
=
5.1, 3J5′,4′ = 2.5 Hz), 6.10 s (1H, NH), 6.06 m (2H, 8-H,
9-H), 5.82 d.d (1H, 6′-H, J6′,1′ = 2.5), 3.59 d.d (1H,
3
1-H), 3.56 d.d (1H, 7-H), 3.38 m (2H, 2-H, 6-H),
(1R,2R,6S,7R)-4-(2,5-Dioxopyrrolidin-1-yl)-4-
azatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione (Va). Yield
80 (a), 77% (b), mp 205–206°C (from propan-2-ol),
Rf 0.68; published data [10]: yield 72%, mp 227–
229°C. IR spectrum, ν, cm–1: 3080, 1815, 1755, 1735,
1270, 718. Found, %: N 10.62. C13H12N2O4. Calculat-
ed, %: N 10.76.
3.29 d.d (1H, 1′-H), 3.10 m (1H, 2′-H), 3.06 d.d (1H,
2
4′-H), 2.92 m (1H, 3′-H), 1.58 d (1H, syn-10-H, J =
8.7 Hz), 1.53 d (1H, anti-10-H), 1.31 d (1H, syn-7′-H,
2J = 8.1 Hz), 1.22 d (1H, anti-7′-H). Found, %: N 8.13.
C18H18N2O5. Calculated, %: N 8.18.
2-[(1R,2R,6S,7R)-(3,5-Dioxo-4-azatricyclo-
[5.2.1.02,6]dec-8-en-4-ylcarbamoyl]benzoic acid
(IVe). Yield 76 (a), 78 (b), 84% (c), mp 160–161°C
(from propan-2-ol), Rf 0.62. IR spectrum, ν, cm–1:
3360, 3250, 3080, 1780, 1735, 1715, 1655, 1605,
1525, 1225, 735. 1H NMR spectrum, δ, ppm: 10.90 s
(1H, COOH), 7.50–7.76 m (4H, Harom), 7.72 s (1H,
NH), 6.07 m (2H, 8-H, 9-H), 3.46 m (2H, 1-H, 7-H),
3.35 m (2H, 2-H, 6-H), 1.56 d (2H, syn-10-H, anti-
10-H). Found, %: N 8.61. C17H14N2O5. Calculated, %:
N 8.59.
(1R,2R,6S,7R)-4-(2,5-Dioxo-2,5-dihydro-1H-pyr-
rol-1-yl)-4-azatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione
(Vb). Yield 82 (a), 78% (b), mp 202–203°C (from
propan-2-ol), Rf 0.77; published data [10]: yield 78%,
mp 217–219°C. IR spectrum, ν, cm–1: 3075, 1805,
1
1790, 1745, 1715, 1280, 720. H NMR spectrum, δ,
3
ppm: 7.35 d (1H, HC=, J = 6.8 Hz), 7.32 d (HC=),
6.13 m (2H, 8-H, 9-H), 3.66 m (1H, 1-H), 3.65 m (1H,
7-H), 3.37 m (1H, 2-H), 3.36 m (1H, 6-H), 1.62 d (1H,
syn-10-H, 2J = 8.7 Hz), 1.57 d (1H, anti-10-H). Found,
%: N 10.90. C13H10N2O4. Calculated, %: N 10.85.
8-[(1R,2R,6S,7R)-(3,5-Dioxo-4-azatricyclo-
[5.2.1.02,6]dec-8-en-4-ylcarbamoyl]naphthalene-1-
carboxylic acid (IVf) was synthesized by stirring
a mixture of 0.50 g (0.28 mmol) of compound II and
0.56 g (0.28 mmol) of 1,8-naphthalic anhydride in
15 ml of acetonitrile for 5 days. Yield 12%, mp 177–
179°C, Rf 0.53. IR spectrum, ν, cm–1: 3350, 3240,
3080, 1780, 1755, 1725, 1685, 1620, 1595, 1530,
1235, 735. Found, %: N 7.53. C21H16N2O5. Calculated,
%: N 7.44.
(1R,2R,6S,7R)-4-[(3aR,7aS)-1,3-Dioxooctahydro-
2H-isoindol-2-yl]-4-azatricyclo[5.2.1.02,6]dec-8-ene-
3,5-dione (Vc). Yield 78 (a), 65 (b), 83% (c), mp 168–
171°C (from ethanol), Rf 0.70. IR spectrum, ν, cm–1:
1
3090, 1805, 1760, 1730, 1270, 735. H NMR spec-
trum, δ, ppm: 6.12 m (2H, 8-H, 9-H), 3.65 m (1H,
1-H), 3.63 m (1H, 7-H), 3.31 m (2H, 2-H, 6-H), 1.61 d
2
(1H, syn-10-H, J = 8.7 Hz), 1.57 d (1H, anti-10-H).
Found, %: N 9.03. C17H18N2O4. Calculated, %: N 8.91.
Bis-imides Va–Vf (general procedure). a. A mix-
ture of 20 mmol of compound IV was heated in 15 ml
of glacial acetic acid under reflux until the reaction
was complete (TLC). The solvent was removed under
reduced pressure, the residue was treated with 5–7 ml
of cold water, and the precipitate was filtered off,
washed on a filter with a small amount of water, dried,
and subjected to further treatment.
(1S,2R,6S,7S)-4-[(1R,2R,6S,7R)-3,5-Dioxo-4-aza-
tricyclo[5.2.1.02,6]dec-8-en-4-yl]-4-azatricyclo-
[5.2.1.02,6]dec-8-ene-3,5-dione (Vd). Yield 95 (a), 83
(b), 78% (c), mp 298–299°C (from ethanol), Rf 0.11;
published data [11]: yield 68%, mp 283–285°C. IR
spectrum, ν, cm–1: 3080, 1805, 1745, 1715, 1255, 740,
1
720. H NMR spectrum, δ, ppm: 6.04 m (4H, 8-H,
9-H, 8′-H, 9′-H), 3.56 m (2H, 1-H, 1′-H), 3.55 m (2H,
7-H, 7′-H), 3.27 m (4H, 2-H, 6-H, 2′-H, 6′-H), 1.56 d
b. A mixture of 1.78 g (10 mmol) of compound II
and 10 mmol of dicarboxylic acid anhydride ІІІa–IIIf
in 20 ml of glacial acetic acid was heated under reflux
until the reaction was complete (TLC). The solvent
was removed under reduced pressure, the residue was
treated with 8–10 ml of cold water, and the precipitate
was filtered off, washed on a filter with a small amount
of water, dried, and subjected to further treatment.
2
(2H, syn-10-H, syn-10′-H, J = 9.4 Hz), 1.51 d (2H,
anti-10-H, anti-10′-H). Found, %: N 8.72. C18H16N2O4.
Calculated, %: N 8.64.
(1R,2R,6S,7R))-4-(1,3-Dioxo-2,3-dihydro-1H-iso-
indol-2-yl)-4-azatricyclo[5.2.1.02,6]dec-8-ene-3,5-di-
one (Ve). Yield 85 (a), 77% (b), mp 191–192°C (from
propan-2-ol), Rf 0.71. IR spectrum, ν, cm–1: 3080,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 7 2007

REACTIONS OF 4-AMINO-4-AZATRICYCLO[5.2.1.02,6-endo]DEC-8-ENE-3,5-DIONE
1023
1
1820, 1790, 1775, 1750, 1620, 1240, 715. H NMR
spectrum, δ, ppm: 7.95–8.06 m (4H, Harom), 6.17 m
(2H, 8-H, 9-H), 3.72 m (1H, 1-H), 3.71 m (1H, 7-H),
1H NMR spectrum, δ, ppm: 7.97–8.10 m (4H, Harom),
3.67 m (1H, 2-H), 3.65 m (1H, 6-H), 3.20 m (2H, 8-H,
10-H), 3.03 m (2H, 1-H, 7-H), 1.43 d (1H, syn-11-H,
2J = 10.4 Hz), 1.12 d (1H, anti-11-H). Found, %:
N 8.72. C17H12N2O5. Calculated, %: N 8.64.
2
3.37 m (2H, 2-H, 6-H), 1.63 d (1H, syn-10-H, J =
9.8 Hz), 1.58 d (1H, anti-10-H). Found, %: N 9.14.
C17H12N2O4. Calculated, %: N 9.09.
2-{(1S,2R,6S,7S,8S,10R)-4-(1,3-Dioxo-2,3-dihy-
dro-1H-benzo[de]isoquinolin-2-yl)}-9-oxa-4-aza-
tetracyclo[5.3.1.02,6.08,10]undecane-3,5-dione (VIe).
Yield 76%, mp 279–281°C (from methanol). IR spec-
trum, ν, cm–1: 3030, 1745, 1715, 1600, 1240, 860.
Found, %: N 7.45. C21H14N2O5. Calculated, %: N 7.48.
2-[(1R,2R,6S,7R)-3,5-Dioxo-4-azatricyclo-
[5.2.1.02,6]dec-8-en-4-yl}-2,3-dihydro-1H-benzo[de]-
isoquinoline-1,3-dione (Vf). Yield 82 (a), 82% (b),
mp 225–227°C (from acetic acid), Rf 0.27. IR spec-
trum, ν, cm–1: 3085, 1805, 1785, 1745, 1710, 1595,
1240, 745. Found, %: N 7.78. C21H14N2O4. Calculated,
%: N 7.82.
(1S,2R,6S,7S,8S,10R)-4-{(1S,2R,6S,7S)-3,5-Di-
oxo-4-azatricyclo[5.2.1.02,6]dec-8-en-4-yl}-9-oxa-4-
azatetracyclo[5.3.1.02,6.08,10]undecane-3,5-dione
(VIf) was synthesized according to the general proce-
dure from 0.50 g (0.15 mmol) of bis-imide Vd and
0.13 g (0.19 mmol) of 50% aqueous hydrogen per-
oxide. Yield 74%, mp 278–279°C (sublimes; from
ethanol), Rf 0.49. IR spectrum, ν, cm–1: 3080, 3030,
Epoxy bis-imides VIa–VIg (general procedure).
A mixture of 5 mmol of bis-imide Va–Ve and 0.58 ml
(10 mmol) of 50% aqueous hydrogen peroxide in
10 ml of 98% formic acid was stirred at room tempera-
ture until the reaction was complete (TLC). Volatile
products were removed under reduced pressure, the
residue was treated with 1–2 ml of cold water, and the
precipitate was off, washed on a filter with a small
amount of cold water, dried in air, and subjected to
additional purification.
1
1780, 1755, 1280, 858, 720. H NMR spectrum, δ,
ppm: 6.11 m (2H, 8′-H, 9′-H), 3.55 m (4H, 2-H, 6-H,
3
2′-H, 6′-H), 3.12 m (1H, 8-H, J = 3.4 Hz), 3.07 m
(2H, 1-H, 7′-H), 3.05 m (1H, 10-H), 2.95 m (2H, 1′-H,
2
7-H), 1.58 d (1H, syn-10′-H, J = 8.7 Hz), 1.52 d (1H,
(1S,2R,6S,7S,8S,10R)-4-(2,5-Dioxopyrrolidin-1-
yl)-9-oxa-4-azatetracyclo[5.3.1.02,6.08,10]undecane-
3,5-dione (VIa). Yield 77%, mp 225–228°C (sublimes;
from ethyl acetate), Rf 0.76. IR spectrum, ν, cm–1:
3030, 1760, 1750, 1730, 1260, 862. Found, %: N 10.05.
C13H12N2O5. Calculated, %: N 10.14.
anti-10′-H), 1.38 d (1H, syn-11-H, 2J = 8.1 Hz), 1.06 d
(1H, anti-11-H). Found, %: N 8.25. C18H16N2O5. Cal-
culated, %: N 8.23.
(1S,2R,6S,7S,8S,10R)-4-{(1R,2R,6S,7R,8S,10R)-
3,5-Dioxo-9-oxa-4-azatetracyclo[5.3.1.02,6.08,10]un-
dec-4-yl}-9-oxa-4-azatetracyclo[5.3.1.02,6.08,10]un-
decane-3,5-dione (VIg) was synthesized from 1.64 g
(5 mmol) of bis-imide Vd and 1.16 ml (20 mmol) of
50% aqueous hydrogen peroxide according to the gen-
eral procedure. Yield 66%, mp 312–315°C (sublimes),
Rf 0.60. IR spectrum, ν, cm–1: 3025, 1805, 1775, 1745,
(1S,2R,6S,7S,8S,10R)-4-(2,5-Dioxo-2,5-dihydro-
1H-pyrrol-1-yl)-9-oxa-4-azatetracyclo[5.3.1.02,6.08,10]-
undecane-3,5-dione (VIb). Yield 95%, mp 270–
272°C (from propan-2-ol), Rf 0.54. IR spectrum, ν,
cm–1: 3035, 1810, 1755, 1740, 1275, 860. H NMR
1
spectrum, δ, ppm: 7.38 m (2H, HC=), 3.61 m (1H,
2-H), 3.60 m (1H, 6-H), 3.13 m (2H, 8-H, 10-H),
3.01 m (2H, 1-H, 7-H), 1.42 d (1H, syn-11-H, J =
10.0 Hz), 1.11 d (1H, anti-11-H). Found, %: N 10.15.
1715, 1280, 860, 855. 1H NMR spectrum, δ, ppm: 3.57
2
3
m (4H, 2-H, 6-H, 2′-H, 6′-H), 3.16 m (4H, 8-H, J8,10
=
3
3.4 Hz, 8′-H, J8′,10′ = 3.4 Hz), 3.10 m (2H, 10-H,
10′-H), 2.96 m (4H, 1-H, 7-H, 1′-H, 7′-H), 1.38 d (2H,
syn-11-H, J = 10.2 Hz, syn-11′-H, J = 10.1 Hz),
1.07 d (2H, anti-11-H, anti-11′-H). Found, %: N 7.74.
C18H16N2O6. Calculated, %: N 7.86.
C13H10N2O5. Calculated, %: N 10.22.
2
2
(1S,2R,6S,7S,8S,10R)-4-[(3aR,7aS)-1,3-Dioxo-
octahydro-2H-isoindol-2-yl]-9-oxa-4-azatetracyclo-
[5.3.1.02,6.08,10]undecane-3,5-dione (VIc). Yield 77%,
mp 211–212°C (from ethanol), Rf 0.87. IR spectrum, ν,
cm–1: 3030, 1810, 1755, 1720, 1280, 860. Found, %:
N 8.54. C17H18N2O5. Calculated, %: N 8.48.
4-{(1S,2R,6S,7S,8S,10R)-(3,5-Dioxo-9-oxa-4-aza-
tetracyclo[5.3.1.02,6.08,10]undec-4-ylamino}-4-oxo-
butanoic acid (VII). Yield 72%, mp 218–220°C (from
ethanol), Rf 0.89. IR spectrum, ν, cm–1: 3350, 3240,
3020, 1790, 1740, 1710, 1690, 1620, 1440, 1280, 860.
1H NMR spectrum, δ, ppm: 12.20 s (1H, COOH),
10.45 s (1H, NH), 3.35 m (2H, 2-H, 6-H), 3.06 m (2H,
8-H, 10-H), 2.91 m (2H, 1-H, 7-H), 1.38 d (1H, syn-
(1S,2R,6S,7S,8S,10R)-4-(1,3-Dioxo-2,3-dihydro-
1H-isoindol-2-yl)-9-oxa-4-azatetracyclo-
[5.3.1.02,6.08,10]undecane-3,5-dione (VId). Yield 83%,
mp 214–215°C (from propan-2-ol), Rf 0.84. IR spec-
trum, ν, cm–1: 1805, 1785, 1755, 1610, 1270, 865.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 7 2007

KAS’YAN et al.
1024
11-H, 2J = 10.0 Hz), 1.05 d (1H, anti-11-H). Found, %:
N 9.50. C13H14N2O6. Calculated, %: N 9.52.
[5.5.1.02,6.08,12]tridec-3-ene-9,11-dione (Xa). Yield
68%, mp 249–251°C (decomp.). IR spectrum, ν, cm–1:
1798, 1755, 1610, 1528, 1342, 1260, 858. Found, %:
N 19.91. C19H16N6O6. Calculated, %: N 19.80.
(1S,2S,6R,7S,8R,12S)-10-[(3aR,7aS)-1,3-Dioxo-
octahydro-2H-isoindol-2-yl]-5-(4-nitrophenyl)-
3,4,5,10-tetraazatetracyclo[5.5.1.02,6.08,12]tridec-3-
ene-9,11-dione (Xb). Yield 77%, mp 189–190°C
(decomp.). IR spectrum, ν, cm–1: 1774, 1752, 1744,
1732, 1598, 1518, 1334, 1276, 848. Found, %: N 17.61.
C23H22N6O6. Calculated, %: N 17.56.
(1S,2R,6S,7S,8S,10R)-4-Amino-9-oxa-4-aza-
tetracyclo[5.3.1.02,6.08,10]undecane-3,5-dione (VIII).
a. A mixture of 1.20 g (3.9 mmol) of epoxy bis-imide
VId and 0.37 g (5.9 mmol) of 80% aqueous hydrazine
hydrate in 10 ml of propan-2-ol was heated for 12 h
under reflux. The mixture was cooled, and the precip-
itate was filtered off, dried in air, and recrystallized
from propan-2-ol.
b. A mixture of 0.80 g (2.5 mmol) of epoxy bis-
imide VIg and 0.24 g (3.8 mmol) of 80% aqueous
hydrazine hydrate in 7 ml of propan-2-ol was heated
for 12 h under reflux. The mixture was cooled, and the
precipitate was filtered off, dried in air, and recrystal-
lized from propan-2-ol. Yield 43 (a), 67% (b),
mp 213–215°C, Rf 0.71. IR spectrum, ν, cm–1: 3335,
(1S,2S,6R,7S,8R,12S)-10-(1,3-Dioxo-2,3-dihydro-
1H-isoindol-2-yl)-5-(4-nitrophenyl)-3,4,5,10-tetra-
azatetracyclo[5.5.1.02,6.08,12]tridec-3-ene-9,11-dione
(Xc). Yield 90%, mp 222–224°C. IR spectrum, ν,
cm–1: 1810, 1785, 1755, 1730, 1605, 1515, 1340, 1235,
1
856. H NMR spectrum, δ, ppm: 8.29 d (2H, Harom),
1
3275, 3020, 1780, 1725, 1685, 1270, 865. H NMR
8.01–8.11 m (4H, Harom), 7.32 d (2H, Harom), 4.86 d
3
spectrum, δ, ppm: 4.91 s (2H, NH2), 3.16 m (2H, 2-H,
(1H, 2-H, J2,6 = 8.5 Hz), 4.02 d (1H, 6-H), 3.80 m
6-H), 2.98 m (2H, 8-H, 10-H), 2.84 m (2H, 1-H, 7-H),
1.32 d (1H, syn-11-H, J = 10.0 Hz), 1.01 d (1H, anti-
(2H, 8-H, 12-H), 3.21 m (2H, 1-H, 7-H), 1.68 d (1H,
syn-13-H, J = 11.6 Hz), 1.17 d (1H, anti-13-H).
2
2
11-H). Found, %: N 14.39. C9H10N2O3. Calculated, %:
Found, %: N 17.72. C23H16N6O6. Calculated, %:
N 14.43.
N 17.79.
2-{(1S,2R,6S,7S,8S,12R)-11-(4-Nitrophenyl)-3,5-
dioxo-4,9,10,11-tetraazatetracyclo[5.5.1.02,6.08,12]-
tridec-9-en-4-ylcarbamoyl}benzoic acid (IX). A mix-
ture of 0.50 g (1.5 mmol) of acid VІe and 0.37 g
(2.3 mmol) of p-nitrophenyl azide in 10 ml of chloro-
form was heated under reflux until the reaction was
complete (TLC). The solvent was removed under re-
duced pressure, and the residue was recrystallized from
propan-2-ol. Yield 79%, mp 171–172°C (decomp.;
from propan-2-ol). IR spectrum, ν, cm–1: 3530, 3400,
1790, 1755, 1720, 1605, 1520, 1345, 1270, 860.
1H NMR spectrum, δ, ppm: 13.50 s (1H, COOH),
(1S,2S,6R,7S,8R,12S)-10-(1,3-Dioxo-2,3-dihydro-
1H-benzo[de]isoquinolin-2-yl)-5-(4-nitrophenyl)-
3,4,5,10-tetraazatetracyclo[5.5.1.02,6.08,12]tridec-3-
ene-9,11-dione (Xd). Yield 75%, mp 247–248°C
(decomp.). IR spectrum, ν, cm–1: 1790, 1750, 1710,
1605, 1600, 1530, 1340, 1240, 855. Found, %: N 16.12.
C27H18N6O6. Calculated, %: N 16.08.
(1S,2S,6R,7S,8R,12S)-10-{(1R,2R,6S,7R)-3,5-Di-
oxo-4-azatricyclo[5.2.1.02,6]dec-8-en-4-yl}-5-(4-nitro-
phenyl)-3,4,5,10-tetraazatetracyclo[5.5.1.02,6.08,12]-
tridec-3-ene-9,11-dione (Xe). A mixture of 1.62 g
(5.0 mmol) of bis-imide Vd and 0.82 g (5 mmol) of
p-nitrophenyl azide in 20 ml of propan-2-ol was heated
under reflux until the reaction was complete (TLC).
The precipitate was filtered off, washed on a filter with
a large amount of propan-2-ol, dried in air, and recrys-
tallized from ethanol. Yield 74%, mp 264–266°C
(decomp.). IR spectrum, ν, cm–1: 3090, 1770, 1750,
8.32 s (1H, NH), 8.12 d (2H, Harom), 7.98–8.06 m (4H,
3
H
arom), 7.25 d (2H, Harom), 4.89 d (1H, 2-H, J2,6
=
9.4 Hz), 4.05 d (1H, 6-H), 3.70 m (2H, 8-H, 12-H),
3.27 m (1H, 1-H), 3.21 m (1H, 7-H), 1.76 d (1H, syn-
13-H, 2J = 10.0 Hz), 1.34 d (1H, anti-13-H). Found, %:
N 17.18. C23H18N6O7. Calculated, %: N 17.14.
Dihydrotriazole derivatives Xa–Xd (general
procedure). A mixture of 5 mmol of bis-imide Va, Vc,
Vd, and Vf and 1.23 g (7.5 mmol) of p-nitrophenyl
azide in 10 ml of chloroform was heated under reflux
until the reaction was complete (TLC). The mixture
was cooled, and the precipitate was filtered off,
thoroughly washed with chloroform on a filter dried in
air, and recrystallized from ethanol.
1
1740, 1610, 1525, 1342, 1270, 855, 760. H NMR
spectrum, δ, ppm: 8.33 d (2H, Harom), 7.30 d (2H,
H
arom), 6.15 m (2H, 8′-H, 9′-H), 4.76 d (1H, 2-H,
3J2,6 = 8.7 Hz), 3.88 d (1H, 6-H), 3.78 m (2H, 8-H,
12-H), 3.69 m (2H, 1′-H, 7′-H), 3.32 m (2H, 2′-H,
6′-H), 3.25 m (1H, 1-H), 3.16 m (1H, 7-H), 1.66 d (1H,
2
2
syn-13-H, J = 11.2 Hz), 1.61 d (1H, syn-10′-H, J =
8.7 Hz), 1.57 d (1H, anti-10′-H), 1.14 d (1H, anti-
13-H). Found, %: N 17.29. C24H20N6O6. Calculated,
%: N 17.21.
(1S,2S,6R,7S,8R,12S)-10-(2,5-Dioxopyrrolidin-1-
yl)-5-(4-nitrophenyl)-3,4,5,10-tetraazatetracyclo-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 7 2007

REACTIONS OF 4-AMINO-4-AZATRICYCLO[5.2.1.02,6-endo]DEC-8-ENE-3,5-DIONE
1025
(1H, anti-10-H). Found, %: N 23.90. C25H18N10O8.
Calculated, %: N 23.88.
(1R,2R,6S,7R,8S,12R)-10-{(1S,2R,6S,7S,8S,12R)-
11-(4-Nitrophenyl)-3,5-dioxo-4,9,10,11-tetraaza-
tetracyclo[5.5.1.02,6.08,12]tridec-9-ene-4-yl}-5-(4-
nitrophenyl)-3,4,5,10-tetraazatetracyclo-
[5.5.1.02,6.08,12]tridec-3-ene-9,11-dione (Xf) was
synthesized in a similar way from 1.62 g (5 mmol) of
bis-imide Vd and 1.46 g (15 mmol) of p-nitrophenyl
azide. Yield 31%, mp 259–260°C (decomp.). IR spec-
trum, ν, cm–1: 1780, 1754, 1735, 1610, 1520, 1345,
(1S,2R,6S,7S,8S,10R)-4-{(3aS,6aR)-1-(4-Nitro-
phenyl)-4,6-dioxo-1,3a,4,5,6,6a-hexahydropyrrolo-
[3,4-d][1,2,3]triazol-5-yl}-9-oxa-4-azatetracyclo-
[5.3.1.02,6.08,10]undecane-3,5-dione (XI) was syn-
thesized in a similar way by heating a mixture of
0.50 g (1.8 mmol) of epoxy bis-imide VIb and 0.30 g
(1.8 mmol) of p-nitrophenyl azide in 15 ml of propan-
2-ol under reflux. Yield 24%, mp 196–199°C
(decomp.). IR spectrum, ν cm–1: 1785, 1760, 1610,
1
1285, 860, 855. H NMR spectrum, δ, ppm: 8.32 d
(2H, Harom), 8.09 d (2H, Harom), 7.34 d (2H, Harom),
3
1
7.24 d (2H, Harom), 4.99 d (1H, 2′-H, J2′,6′ = 9.3 Hz),
1530, 1350, 1325, 870, 860. H NMR spectrum, δ,
3
4.88 d (1H, 2-H, J2,6 = 8.7 Hz), 4.12 d (1H, 6′-H),
ppm: 8.32 d (2H, Harom), 8.09 d (2H, Harom), 7.34 d
(2H, Harom), 7.23 d (2H, Harom), 6.28 d (1H, 1′-H,
3J1′,5′ = 10.6 Hz), 5.58 d (1H, 5′-H), 4.77 d (1H, 2-H,
3J2,6 = 8.7 Hz), 3.93 d (1H, 6-H), 3.78 m (1H, 8-H),
3.66 m (1H, 12-H), 3.14 m (1H, 1-H), 2.59 m (1H,
3.92 d (1H, 6-H), 3.78 m (4H, 8-H, 12-H, 8′-H, 12′-H),
3.31 m (2H, 1-H, 1′-H), 3.29 m (2H, 7-H, 7′-H), 1.66 d
(2H, syn-13-H, 2J = 11.2 Hz, syn-13′-H, 2J = 11.2 Hz),
1.16 d (2H, anti-13-H, anti-13′-H). Found, %: N 21.52.
C30H24N10O8. Calculated, %: N 21.46.
2
7-H), 1.69 d (1H, syn-13-H, J = 11.2 Hz), 1.18 d
(1H, anti-13-H). Found, %: N 19.21. C19H14N6O7. Cal-
culated, %: N 19.17.
(1S,2S,6R,7S,8R,12S)-10-(2,5-Dioxo-2,5-dihydro-
1H-pyrrol-1-yl)-5-(4-nitrophenyl)-3,4,5,10-tetraaza-
tetracyclo[5.5.1.02,6.08,12]tridec-3-ene-9,11-dione
(Xg). A mixture of 0.40 g (1.6 mmol) of bis-imide Vb
and 0.25 g (1.6 mmol) of p-nitrophenyl azide in
10 ml of chloroform was heated under reflux until the
reaction was complete (TLC). The mixture was cooled,
and the precipitate was filtered off, thoroughly washed
with chloroform on a filter, dried in air, and recrystal-
lized from chloroform. Yield 73%, mp 216–218°C. IR
spectrum, ν, cm–1: 1805, 1760, 1610, 1520, 1345,
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3
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(1S,2S,6R,7S,8R,12S)-10-{(3aS,6aR)-1-(4-Nitro-
phenyl)-4,6-dioxo-1,3a,4,5,6,6a-hexahydropyrrolo-
[3,4-d][1,2,3]triazol-5-yl}-5-(4-nitrophenyl)-3,4,5,10-
tetraazatetracyclo[5.5.1.02,6.08,12]tridec-3-ene-9,11-
dione (Xh) was synthesized in a similar way by
heating a mixture of 0.40 g (1.6 mmol) of bis-imide
Vb and 0.75 g (4.8 mmol) of p-nitrophenyl azide in
15 ml of chloroform under reflux. Yield 43%, mp 195–
198°C. IR spectrum, ν, cm–1: 1810, 1795, 1760, 1605,
1
1525, 1345, 870, 860. H NMR spectrum, δ, ppm:
8.26 d (2H, Harom), 7.37 d (2H, Harom), 6.31 d (1H,
3
1′-H, J1′,5′ = 10.6 Hz), 5.71 d (1H, 5′-H), 3.62 m (2H,
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2
7-H), 1.42 d (1H, syn-10-H, J = 10.0 Hz), 1.11 d
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 7 2007

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