Structure and reactivity of bicyclo[2.2.1]hept-2-ene-endo-5,endo-6- dicarboxylic (endic) acid hydrazide

Article abstract of DOI:10.1007/s11178-005-0305-9

Establishing of the structure of hydrazinolysis product obtained from bicyclo[2.2.1]hept-2-ene-endo-5, endo-6-dicarboxylic (endic) acid was performed by preparation of the compound under alternative conditions followed by comparison of the characteristics

Full text of DOI:10.1007/s11178-005-0305-9

Russian Journal of Organic Chemistry, Vol. 41, No. 8, 2005, pp. 1122−1131. Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 8, 2005,
pp. 1145−1154.
Original Russian Text Copyright © 2005 by Kas’yan, Tarabara, Bondarenko, Shishkina, Shishkin, Musatov.
.
Structure and Reactivity
of Bicyclo[2.2.1]hept-2-ene-endo-5,endo-6-dicarboxylic (endic) Acid
Hydrazide
L.I. Kas’yan1, I.N. Tarabara1, Ya.S. Bondarenko1, S.V. Shishkina2,
O.V. Shishkin2, and V.I. Musatov2
1Dnepropetrovsk National University, Dnepropetrovsk,49050 Ukraine
2Institute of Single Crystals, National Academy of Sciences of Ukraine, Khar’kov, Ukraine
Received November 23, 2004
Abstract—Establishing of the structure of hydrazinolysis product obtained from bicyclo[2.2.1]hept-2-ene-endo-
5,endo-6-dicarboxylic (endic) acid was performed by preparation of the compound under alternative conditions
followed by comparison of the characteristics and spectral parameters of the resulting substances, and also by
1
quantum-chemical calculations by the density functional method of the chemical shifts in H and 13C NMR
spectra of different reaction products. The X-ray diffraction analysis of the hydrazide was also carried out. The
compound obtained was assigned a structure of N-aminobicyclo[2.2.1] hept-2-ene-endo-5,endo-6-dicarboximide.
The products were prepared by its reactions with arylsulfonyl chlorides, benzoyl chlorides, m-tolyl and p-toluene-
sulfonyl isocyanates, phenyl isothiocyanate, with o-nitrobenzaldehyde, and oxiranes (1,2-epoxycyclohexane and
2,3-epoxypropylcarbazole). The aromatic sulfonamides, carboxamides, and ureas were epoxidized by performic
acid obtained in situ from the formic acid and hydrogen peroxide. Products of [3+2]-cycloaddition of aryl azides to
the strained double bond in the N-aminobicyclo[2.2.1] hept-2-ene-endo-5,endo-6-dicarboximide and its derivatives.
The structures of compounds obtained were confirmed by their IR, 1H and 13C NMR spectra.
Organic derivatives of hydrazine are extensively used
in medicine as pharmacological agents exhibiting
tuberculocidal, anticancer, radioprotection, antidepressant,
psychotherapeutic, and other kinds of biological activity
[1].Among these compounds plant growth regulators and
stimulators were found [2], and also herbicides [3].
Although the reactions of unsubstituted hydrazine with
the endic anhydride has been studied since the beginning
of nineteen seventies the results obtained are ambiguous.
Actually, in [5, 6] the reaction product and its analogs
were regarded as 1,2,3,4-tetrahydro-5,8-methano-
phthalazine (II). On the other hand, Augustin and
Reinemann who proved the possibility to obtain substituted
azines from maleic and phthalic anhydrides assigned to
the hydrazide of the endic anhydride the structure of
aminoimide III [7]. Both viewpoint were further
additionally supported [8–11] but strict proofs of the
structure of hydrozinolysis product obtained from endic
anhydride were lacking.
In contrast to a wide group of hydrazides of aliphatic
and aromatic compounds and hydrozinolysis products of
dicarboxylic (maleic, succinic, and phthalic) acids
anhydrides analogous derivatives of the bicyclo[2.2.1]-
hept-2-ene-endo-5,endo-6-dicarboxylic (endic) acid are
poorly studied. We demonstrated considerable difference
in reaction conditions and products of endic anhydride
(I) with amines and hydrazines; anhydride I reacted with
a wide range of alkyl-, aryl-, and heterylamines in benzene
at room temperature affording amidoacids; the latter
could be converted into carboximides by boiling in the
glacial acetic acid. The reactions of endic anhydride with
alkyl- and arylhydrazines under mild conditions in contrast
to reactions with amines furnished imide forms. The
intermediate hydrazidoacids were isolated only seldom
[4].
To establish the structure of the reaction product of
anhydride I and hydrazine hydrate we first evaluated the
7
1
2
6
O
O
O
O
N
4
5
3
NH
O
O
N
NH2
O
H
I
II
III
1070-4280/05/4108-1122©2005 Pleiades Publishing, Inc.

STRUCTURE AND REACTIVITY OF BICYCLO[2.2.1]HEPT-2-ENE-endo-5,endo-6-DICARBOXYLICACID... 1123
Shielding constants and chemical shifts calculated by method GIAO-B3LYP/6-311++G**//B3LYP/6.31G* NMR for compounds
II and III
Shielding constant, σ
Chemical shift, δ, ppm.
Nucleus
Experimental data
III
III
II
II
H1,4
H2,3
H5,6
H7s
28.3434
25.3514
28.8295
30.3680
30.6387
26.2270
127.6370
37.5815
135.1720
129.9295
15.4627
28.6120
25.5637
28.9542
30.2271
30.5234
27.4580
131.1737
39.9224
132.7590
126.7084
5.8519
3.5566
6.5486
3.0705
1.5320
1.2613
5.6730
56.4630
146.5185
48.9280
54.1705
168.6373
3.2880
6.3363
2.9458
1.6729
1.3766
3.33
6.04
3.22
1.70
1.49
4.09
44.9
134.7
44.4
52.2
H7a
HNH
C1,4
C2,3
C5,6
C7
4.4420
52.9263
144.1776
51.3410
57.3916
178.2481
C=O
175.0
agreement between the experimental data and the
calculations of the chemical shifts for aminoimide III.
According to calculations the chemical shifts of protons
and carbon nuclei in the molecule of aminoimide III
decrease in the following order coinciding with that
previously established by calculation for substituted
hydrazines [4]: H2, H3 > H1, H4 > H5, H6 > H7s, H7a ; C2,
C3 > C7 > C1, C4 > C5, C6.
heats of formation and strains in the alternative structures
II and III by molecular mechanics method. The
calculation results show significant energy feasibility of
the five-membered imide III: the heats of formation
for structures II and III equal respectively –69.00 and
–74.88 kcal mol−1, strain energies are 22.5 and
17.2 kcal mol−1. Structure III possesses an enhanced
angle strain (Baeyer strain), lower value of torsion strain
and of van der Waals interactions.
The structure of compound III was proved by X-ray
diffraction analysis (the numbering of atoms used in
discussion is given in Fig. 1). According to X-ray data
the five-membered heterocycle is planar with an accuracy
Hydrazinolysis of anhydride I was carried out by two
known procedures (heating of the anhydride mixture with
25% water solution of hydrazine in alcohol [7] or boiling
equimolar amounts of the anhydride with 80% aqueous
hydrazine hydrate in alcohol for 5 h [5]), and also similarly
to the conditions we had previously used in reaction of
the endic anhydride with monosubstituted hydrazines (in
the cold in a benzene solution [4]). In all cases were
isolated identical reaction products in respective yields
94.3, 91.0, and 92.5%. All products had the same IR, 1H
and 13C NMR spectra. The IR spectrum contained bands
at 3338 and 3222 cm–1 corresponding to vibrations of NH2
group[12, 13], vibration band of the carbonyl groups in
the imide fragment (1767 and 1700 cm–1), and also bands
in the regions 3063 and 724 cm–1 belonging to the
vibrations of the strained double bond in the bicyclic
skeleton [13].
°
of 0.01 A. The N1 atom possesses planar-trigonal
configuration (the sum of bond angles equals to 359.8°),
and N2 has a pyramidal configuration (the sum of bond
angles is 313°). The hydrogen atoms of the amino group
are turned to the O1 atom [torsion angles are C8N1N2HA
54(1) and C8N1N2HB –55(1)°]. This orientation of the
amino group leads to location of the unshared electron
pair of the atom N2 in the plane of the heterocycle;
therefore this electron pair is not involved into the
conjugation with the π-system of the five-membered ring.
In general the amino group is bent in the direction of the
carbonyl group C9=O2: the bond angles C8N1N2 and
C9N1N2 equal to 125.0(2) and 120.9(2)° respectively.
A nonequivalence of N1–C9 and N1–C8 bonds was also
°
observed [1.387(2) and1.379(2) Arespectively] as
1
The chemical shift values in the H and 13C NMR
°
compared with the average value of 1.372 A [15].
spectra of compound obtained are presented in the table
alongside the results of quantum-chemical calculations
of these parameters performed by nonempirical
procedure GIAO-B3LYP/6-311++G**//B3LYP/6.31G*
[14]. The data in the table considerably facilitate the
assignment of the signals and evidence the good
The bicyclic fragment and the five-membered
heterocycle are fused by the cis-type (torsion angle
H7C7C6H6 1°). The C4–C7 and C1–C6 bonds in the
bicyclic fragment are slightly elongated [1.564(2) and
°
1.563(2) A respectively] as compared with the mean
RUSSIAN JOURNALOF ORGANIC CHEMISTRY Vol. 41 No. 8 2005

KAS’YAN et al.
1124
C5
C4
ArC(O)Cl,
C5H5N
O
N
O
N
C1
C7
NHC(O)Ar
C6
NH2
O
O
Va, Vc
III
C9
C3
C2
O2
N2
Ar = C6H4NO2-p (a), C6H4Cl-o (b).
C8
N1
respectively. By the first procedure compound IVb was
also prepared in a high yield (85.2%).
O1
Reaction of aminoimide III with p-nitro- and o-chloro-
benzoyl chlorides was carried out in pyridine in the cold.
Both compounds we have previously prepared by reaction
of endic anhydride with acylhydrazides, and they have
been described in [4]. Their ppreparation by a new
method was an additional confirmation of their structure.
Fig. 1. Structure of the molecule of N-aminobicyclo[2.2.1]hept-
2-ene-endo-5,endo-6-dicarboximide (III) according to X-ray
diffraction analysis.
°
The derivatives of urea and thiourea VIa–VIc were
obtained by reaction of aminoimide III with m-tolyl
isocyanate, p-toluenesulfonyl isocyanate, and phenyl
isothiocyanate performed in benzene solutions with
addition of chloroform at room temperature (TLC
monitoring). Phenylthiourea VIc was described before
[8], and the characteristics of compound we obtained
were consistent with the published data
value 1.542 A; this feature is characteristic of this type
cage-like compounds [16].
The molecules of aminoimide III in the crystal form
stacks along the crystallographic direction (0) in
consequence of weak intermolecular hydrogen bonds C7–
H7 O2' (x, y – 1, z): H O’ 2.55 A, C–H...O’ 143°.
The hydrogen atoms of the amino group are not involved
into the hydrogen bonds in contrast to the common case
of crystal structures containing both amino and carbonyl
groups.
°
...
...
The boiling of equimolar amounts of aminoimide III
and O-nitrobenzaldehyde in ethanol gave rise to imine
VII.
Compound III contains in its structure several reaction
sites, first of all an amino group and a strained double
bond. The reactivity of the amino group of compound III
is proved by reactions with p-toluene-, p-bromobenzene-,
and p-nitrobenzenesulfonyl chlorides in the presence of
bases.
The reactions of aminoimide III with two epoxy
compounds (epoxycyclohexane and 2,3-epoxy-
propylcarbazole) were carried out in ethyl acetate and
2-propanol respectively; in the first case 2-propanol was
used as activator of the epoxy ring opening. From the
known data we expected in formation of aminoalcohols
VIIIa and VIIIb to occur a stereospecific trans-diaxial
epoxy ring opening in epoxycyclohexane [17, 18], and in
carbazole-containing oxirane a regioselective attack was
presumed of the amino group on the sterically more
accessible primary carbon atom (Krasusky rule) [19].
Sulfonylhydrazide IVa was obtained in pyridine
(procedure a), in chloroform at the use of equimolar
amounts of aminoimide III, tosyl chloride, and
triethylamine (procedure b), and in a two-phase
system(ether–20% water solution of potassium
hydroxide) (procedure c) in yields 80.4, 69.9 and 61.4%
In the IR spectra of aminoimide III derivatives the
absorption bands of the carbonyl groups from the imide
fragment appear in the regions 1790–1750 and 1730–
1705 cm–1, and also absorption bands of NH bonds
included into amide and sulfonamide groups are observed.
The sulfonamide groups of compounds IVa, IVb, and
VIb give rise to absorption bands in the regions 1365–
1350 and 1185–1170 cm–1, and amide groups of com-
pounds Va, Vb, VIa, and VIb are represented by a set
of “amide” bands in the regions 1680–1630, 1590–1530,
Ar = C6H4CH3-p (a), C6H4Br-p (b), C6H4NO2-p (c).
RUSSIAN JOURNALOF ORGANIC CHEMISTRY Vol. 41 No. 8 2005

STRUCTURE AND REACTIVITY OF BICYCLO[2.2.1]HEPT-2-ENE-endo-5,endo-6-DICARBOXYLICACID... 1125
O
N
NO2
O
N
CH3
N CH
NHC(O)NH
O
O
VIa
VII
O
N
O
N
OH
NHC(O)NHSO2
CH3
O
NHCH
2 CH CH2 N
O
VIb
VIIIa
O
N
NHC(S)NH
O
N
O
OH
H
VIb
NH
and 1270–1240 cm–1, corresponding to the stretching
vibrations of the carbonyl groups, bending vibrations of
the N–H bonds, and stretching vibrations of the C–N
bonds[12]. In the IR spectrum of thiours VIc lacks the
band “amide I” and an absorption is observed in the region
1335 cm–1 due to the vibrations of the thiocarbonyl group
[12].
O
VIIIb
shifts for the most protons of the skeleton were observed
in the spectrum of amide Va, the minimum values were
found for aminoalcohol VIIIb. In the spectra of all
derivatives of compound III the chemical shifts of the
methylene bridge protons (H7s, H7a) were equivalent. In
all cases the signals from the 1H nuclei in the substituents
attached to nitrogen atoms were detected.
Note the shift of the absorption bands of benzoyl-
hydrazines Va and Vb compared with sulfonylhydrazines
from the region 3250–3240 to the region 3520–
3470 cm–1 indicating the presence of an enol tautomer.
The existence of a tautomeric equilibrium in amides of
this series obtained by another procedure had been
considered before basing on the analysis of the 13C NMR
spectra [4]. The characteristic feature of the IR spectra
of aminoalcohols VIIIa and VIIIb is the presence of
absorption bands belonging to hydroxy and amino groups
in the region 3350–3250 cm–1. The strained double bond
gives rise to the bands in the regions 3080–3060 and 730–
715 cm–1 corresponding to the stretching and bending
vibrations of the =C–H bonds [13].
In the 1H NMR spectra of compounds IVa, Va, Vb,
and VIIIb all characteristic signals are present proving
the assumed structures of compounds synthesized. The
assignment of the signals was carried out applying the
already mentioned nonempirical calculations of the
chemical shifts for the parent substance of this series,
aminoimide III. The maximum values of the chemical
The presence of a strained double bond in the
molecules of the N-substituted aminoimides provided a
possibility to carry out reactions with peracids and aryl
azides. The synthesis of epoxy derivatives is especially
promising for among such compounds biologically active
substances occur with a widest range of the
pharmacological effect [20]. The search for the optimum
procedure of their preparation requires evaluation of the
substrates structure and oxidants characteristics [21]. In
particular, the epoxidation of derivatives IV–VI originating
from aminoimide III was best performed by the action
of performic acid obtained in situ from 98% formic acid
and 50% water solution of hydrogen peroxide.
The successful application of the performic acid is
due to the imide structure including several electron-
withdrawing moieties that decrease the nucleophilic reac-
tivity of the olefin and require the use of sufficiently strong
peroxyacid [21]. The electron-withdrawing dicarboximide
RUSSIAN JOURNALOF ORGANIC CHEMISTRY Vol. 41 No. 8 2005

KAS’YAN et al.
1126
completion).
In the IR spectra of triazolines Xa−Xc the absorption
O
O
N
O
N
HCO3H
bands of the carbonyl groups from the imide fragments
(1790–1770, 1730–1710) and from NH group (3340–3200
cm–1) are retained. The medium band in the region 1600–
1590 cm–1 lacking in the IR spectra of initial compounds
belongs apparently to the stretching vibrations of the N=N
NHX
NHX
O
O
IVa, IVb_VIa, VIb
IXa_IXf
IX, X = SO2C6H4CH3-p (a), SO2C-6H4Br-p (b),
C(O)C6H4NO2-p (c), C(O)C6H4Cl-o (d),
1
bond from the triazoline moiety [12]. The H NMR
spectrum of compound Xa presented on Fig.2 is essentially
different from the spectra of compounds IXa and IXc
first of all due to the asymmetry of the triazoline molecule
resulting in considerable inequiality of chemical shifts of
the protons attached to the carbon skeleton, in particular,
those involved into the triazoline fragment (4.63 and 3.84
ppm). The resonances from the methylene bridge protons
appear at 1.60 and 1.10 ppm; also the spectrum contains
the proton signals from NH2 group (4.95 ppm) and the
para-substituted benzene ring
C(O)NHC6H4CH3-m(e), C(O)NHSO2C6H4CH3-p (f).
13
3
4N
N
1
8
2
12
O
N
O
N
ArN3
7
5
11
10
6
Ar
NHX
9
N
NHX
O
O
Xa_Xc
III, IVa
X, X = H, Ar = C6H4NO2-p (a), C6H4Br-p (b);
X = SO2C6H4CH3-p,Ar = C6H4Br- (c).
EXPERIMENTAL
moiety prevents the negative effects from the application
of the performic acid (the hydrolysis and acidolysis of
the arising epoxide and the accompanying molecular
rearrange-ments) for it destabilizes the intermediate
carbocations.
IR spectra were recorded on spectrophotometer UR-
20 from samples prepared as KBr pellets. H NMR
1
spectra were registered on spectrometers Bruker DRX-
500 (operating frequency 500 MHz) and Varian VXR-
Unity (operating frequency 200 MHz) from solutions of
compounds in deuterodimethyl sulfoxide or deutero-
chloroform using TMS as internal reference. The
13C NMR spectra were measured on spectrometer Inova-
400 at operating frequency 100.6 MHz. Reactions
progress was monitored and purity of compounds
synthesized was checked by TLC on Silufol UV-254
plates, eluent ether or a mixture ether–2-propanol, 20:1;
development in iodine vapor. Elemental analysis was
carried out on a Carlo Erba analyzer.
The structure of epoxides was confirmed by spectral
methods. In the IR spectra of the compounds strong bands
are present in the region 860–855 cm–1 originating from
the stretching vibrations of oxygen−carbon bonds in the
epoxy moieties of the epoxynorbornane molecules [22].
1
In the H NMR spectra of epoxy compounds IXa and
IXc the following changes are observed compared to
the spectra of initial olefins IVa and Va: the signals from
protons H2, H3 are shifted to the region 3.30–3.50 ppm,
and a doublet from one of the methylene bridge proton
(H7a) is shifted upfield (0.99 and 1.08 ppm respectively)
due to the magnetically anisotropic influence of the epoxy
group on the nucleus located directly over the plane of
the three-membered ring [23].
Crystals of compound III monoclinic. C9H10N2O2.At
20°C a 11.525(3), b 11.717(3)A, β 100.73(2)°, V 820.9(3)
3, Mr 178.19, Z 4; space group P21/C, dcalc 1.442 g/cm3,
μ(MOKα) 0.104 mm–1, F(000) 376. The unit cell param-
eters and intensity of 1681 reflections (1451 independent,
Rint 0.026) were measured on an automatic four-circle
diffractometer Siemens P3/PC (MOKα, graphite
monochromator, θ/2θ-scanning, 2θmax 50°).
The structure was solved by the direct method applying
the software package SHELXTL [26]. The positions of
hydrogen atoms were revealed from the difference
synthesis of the electron density and refined by the rider
model with Uiso = 1.2Ueq of the nonhydrogen atom linked
to the given hydrogen, save the hydrogen atoms of the
The strain in the double bond [13] favors reactions of
substituted norbornenes involving the formation of cyclic
transition states, in particular, reactions of 1,3-dipolar
cycloaddition of aryl azides [24]. In contrast to the parent
compound of the series, norbornene, the other bicyclo-
[2.2.1]hept-2-enes virtually were not brought into reactions
with aryl azides [25]. We carried out reactions of
compounds III and IVa with p-nitrophenyl and p-bromo-
nitrophenyl azides by boiling the mixtures of equimolar
amounts of reagents (TLC monitoring of the reaction
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STRUCTURE AND REACTIVITY OF BICYCLO[2.2.1]HEPT-2-ENE-endo-5,endo-6-DICARBOXYLICACID... 1127
1
Fig. 2. H NMR spectrum of 5-p-nitrophenyl-10-amino-3,4,5,10-tetraazatricylo[5.5.1.02,6exo.08,12endo]tridec-3-ene-9,11-dione (Xa)
(DMSO-d6), δ, ppm.
amino group that were subjected to refining in the isotropic
approximation. The structure was refined by F2 in a full-
matrix least-squares method in anisotropic approximation
for nonhydrogen atoms till wR2 0.107 for 1419 reflections
[R1 0.041 for 1033 reflections with F > 4σ(F), S 1.048].
Atomic coordinates are available from the authors.
13C NMR spectrum, δ, ppm: 175.0 (C=O), 134.7 (C2,
C3), 52.2 (C7), 44.9 (C1, C4), 44.4 (C5, C6). Found, %:
N 15.70. C9H10N2O2. Calculated, %: N 15.73.
Reaction of aminoimide III with substituted
arylsulfonyl chlorides. a. To a solution of 0.50 g (2.8
mmol) of aminoimide III in 5 ml of pyridine was added
at stirring 2.8 mmol of an appropriate arylsulfonyl chloride.
The stirring was continued till reaction completion (TLC
monitoring). The solvent was removed, the residue was
treated with a mixture of chloroform with water, 1:1, the
organic layer was washed in succession with water
solution of hydrochloric acid, with saturated solution of
sodium hydrogen carbonate, and with water. The organic
layer was separated, dried with calcined magnesium
sulfate, and the solvent was removed. The reaction
product was recrystallized from 2-propanol. Compounds
IVa and IVb were prepared by this procedure.
N-Aminobicyclo[2.2.1]hept-2-ene-endo-5,endo-6-
dicarboximide (III). Method a was reported in [7]. Yield
94.3%, mp 146–147°C (publ.: yield 96%, mp 145–147°C
[7]).
Method b was published in [5]. Yield 91.0%, mp 146–
147°C (publ.: yield 91%, mp 141–144°C [5]).
c. To a dispersion of 4.92 g (0.03 mol) of endic
anhydride in 15 ml of benzene was added at stirring
1.98 g (1.9 ml, 0.03 mol) of 80% water solution of
hydrazine hydrate. The stirring was continued till reaction
completion (TLC monitoring). The separated crystals of
compound III were filtered off, dried in air, and
recrystallized from 2-propanol. Yield 92.5%, mp 146–
147°C, Rf 0.35 (ether–2-propanol, 20:1). IR spectrum,
cm–1: 3338, 3222, 3063, 1767, 1700, 1400, 1220, 724.
1H NMR spectrum, δ, ppm: 6.04 m (2H, H2, H3),
4.09 s (1H, NH), 3.33 m (2H, H1, H4), 3.22 m (2H, H5,
b. To a solution of 0.50 g (2.8 mmol) of aminoimide
III and 0.28 g (0.39 ml, 2.8 mmol) of triethylamine in
5 ml of chloroform was added at stirring 0.53 g (2.8 mmol)
of p-toluenesulfonyl chloride. The stirring was continued
till reaction completion (TLC monitoring). The reaction
mixture was treated in succession with 20% water solution
of hydrochloric acid, with saturated solution of sodium
2
H6), 1.70 d (1H, H7s, J7s,7a 9.0 Hz), 1.49 d (1H, H7a).
RUSSIAN JOURNALOF ORGANIC CHEMISTRY Vol. 41 No. 8 2005

KAS’YAN et al.
1128
hydrogen carbonate, and with water. The organic layer
was separated, dried with calcined magnesium sulfate,
and the solvent was removed. The reaction product was
recrystallized from 2-propanol.
was separated, dried with calcined magnesium sulfate,
and the solvent was removed. The reaction product was
recrystallized from 2-propanol.
N-(p-Nitrobenzoylamino)bicyclo[2.2.1]hept-2-
ene-endo-5,endo-6-dicarboximide (Va). Yield 93.5%,
mp 137–138°C, Rf 0.65 (ether–2-propanol, 20:1). IR
spectrum, cm–1: 3520, 3065, 1770, 1715, 1600, 1525, 1365,
1350, 1280, 725. 1H NMR spectrum, δ, ppm: 8.35 d (2H,
Harom), 8.10 d (2H, Harom), 6.13 m (2H, H2, H3), 6.05 s
(1H, NH), 3.32 m (2H, H1, H4), 3.32 m (2H, H5, H6),
1.58 m (2H, H7s, H7a). Found, %: N 12.70. C16H13N3O5.
Calculated, %: N 12.84.
c. To a mixture of 0.50 g (2.8 mmol) of aminoimide
III and 0.79 g (0.67 ml) of 20% water solution of
potassium hydroxide in 10 ml of ether was added
2.8 mmol of an appropriate arylsulfonyl chloride. The
stirring was continued till reaction completion (TLC
monitoring). The solvent was removed, the residue was
treated with a mixture of chloroform with water, 1:1, the
organic layer was washed in succession with water
solution of hydrochloric acid, with saturated solution of
sodium hydrogen carbonate, and with water. The organic
layer was separated, dried with calcined magnesium
sulfate, and the solvent was removed. Compounds IVa
and IVc were prepared by this procedure.
N-(o-Chlorobenzoylamino)bicyclo[2.2.1]hept-2-
ene-endo-5,endo-6-dicarboximide (Vb). Yield 78.5%,
mp 108–110°C, Rf 0.69 (ether–2-propanol, 20:1). IR
spectrum, cm–1: 3470, 3060, 1790, 1730, 1680, 1595, 1310,
1205, 715. 1H NMR spectrum, δ, ppm: 7.60–7.32 m (4H,
Harom), 6.15 m (2H, H2, H3), 4.83 s (1H, NH), 3.38 m
(2H, H1, H4), 3.26 m (2H, H5, H6), 1.70 d (1H, H7s),
1.62 d (1H, H7a). Found, %: N 8.81. C16H13ClN2O3.
Calculated, %: N 8.85.
N-(p-Toluenesulfonylamino)bicyclo[2.2.1]-hept-
2-ene-endo-5,endo-6-dicarboximide (IVa). Yield 80.4
(a), 69.9 (b), 61.4% (c), mp 181–182°C. Rf 0.87 (ether–
2-propanol, 20:1). IR spectrum, cm–1: 3250, 3060, 1810,
1740, 1605, 1360, 1185, 715. 1H NMR spectrum, δ, ppm:
7.73 d (2H, Harom), 7.46 d (2H, Harom), 5.99 m (2H, H2,
H3), 4.79 s (1H, NH), 3.32 m (2H, H1, H4), 3.23 m
(2H, H5, H6), 2.43 s (3H, CH3), 1.54 d (1H, H7s, 2J7s,7a
8.2 Hz), 1.48 d (1H, H7a). Found, %: N 8.45.
C16H16N2O4S. Calculated, %: N 8.43.
Reaction of aminoimide III with isocyanates and
isothiocyanates. To a dispersion of 0.50 g (2.8 mmol)
of aminoimide III in 5 ml of anhydrous benzene was
added 2.8 mmol of m-tolyl isocyanate, p-toluenesulfonyl
isocyanate, or phenyl isothiocyanate. The precipitated
crystals of reaction products were filtered off, washed
with benzene, dried in air, and recrystallized from benzene
or 2-propanol.
N-(p-Bromophenylsulfonylamino)bicyclo-[2.2.1]-
hept-2-ene-endo-5,endo-6-dicarboximide (IVb). Yield
85.2%, mp 145–146°C, Rf 0.72 (ether–2-propanol, 20:1).
IR spectrum, cm–1: 3235, 3063, 1760, 1710, 1570, 1360,
1185, 735. Found, %: N 7.09. C15H13BrN2O4S.
Calculated, %: N 7.05.
N-(m-Tolylureido)bicyclo[2.2.1]hept-2-ene-endo-
5,endo-6-dicarboximide (VIa). Yield 52.0%, mp 207–
208°C (2-propanol), Rf 0.31 (ether–2-propanol, 20:1). IR
spectrum, cm-1: 3340, 3230, 3060, 1795, 1735, 1670, 1580,
1500, 1100, 730. Found, %: N 13.45. C17H17N3O3.
Calculated, %: N 13.50.
N-(p-Nitrophenylsulfonylamino)bicyclo-[2.2.1]-
hept-2-ene-endo-5,endo-6-dicarboximide (IVc). Yield
61.4%, mp 181–182°C, Rf 0.76 (ether–2-propanol, 20:1).
IR spectrum, cm–1: 3280, 3060, 1720, 1610, 1550, 1365,
1190, 730. Found, %: N 11.48. C15H13N3O6S. Calculated,
%: N 11.57.
N-(p-Toluenesulfonylureido)bicyclo[2.2.1]-hept-
2-ene-endo-5,endo-6-dicarboximide (VIb). Yield
72.0%, mp 210–211°C (2-propanol), Rf 0.61 (ether–
2-propanol, 20:1). IR spectrum, cm–1: 3300, 3270, 3065,
1800, 1735, 1700, 1600, 1350, 1170, 735. Found, %:
N 11.15. C17H17N3O5S. Calculated, %: N 11.20.
N-(Phenylthioureido)aminobicyclo[2.2.1]hept-2-
ene-endo-5,endo-6-dicarboximide (VIc). Yield 80.2%,
mp 204–206°C (benzene) [7], Rf 0.85 (ether–2-propanol,
20:1). IR spectrum, cm–1: 3315, 3215, 3055, 1760, 1715,
1600, 1530, 1335, 1200, 725. Found, %: N 13.40.
C16H15N3O2S. Calculated, %: N 13.42.
Reaction of aminoimide III with substituted
benzoyl chlorides. To a solution of 0.50 g (2.8 mmol)
of aminoimide III in 5 ml of pyridine was added at stirring
2.8 mmol of substituted benzoyl chloride. The stirring was
continued till reaction completion (TLC monitoring). The
solvent was removed, the residue was treated with
a mixture of chloroform with water, 1:1, the organic layer
was washed in succession with water solution of
hydrochloric acid, with saturated solution of sodium
hydrogen carbonate, and with water. The organic layer
N-(O-Nitrobenzylideneamino)bicyclo[2.2.1]-
hept-2-ene-endo-5,endo-6-dicarboximide (VII).
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STRUCTURE AND REACTIVITY OF BICYCLO[2.2.1]HEPT-2-ENE-endo-5,endo-6-DICARBOXYLICACID... 1129
A mixture of 0.50 g (2.8 mmol) of aminoimide III and
0.42 g (2.8 mmol) of O-nitrobvenzaldehyde in ethanol
was heated at reflux for 6 h. The light-yellow crystals
precipitated on cooling were filtered off, dried in air, and
recrystallized from 96% ethanol. Yield 67%, mp 136–
137°C, Rf 0.60 (ether). IR spectrum, cm–1: 3070, 1740,
1615, 1540, 1360, 1340, 1190, 710. Found, %: N 13.47.
C16H13N3O4. Calculated, %: N 13.50.
20:1). IR spectrum, cm–1: 3240, 1690, 1590, 1520, 1360,
1165, 860. 1H NMR spectrum, δ, ppm: 10.81 s (1H, NH),
7.67 d (2H, Harom), 7.36 d (2H, Harom), 3.32 m (2H, H2,
H3), 3.22 m (2H, H5, H6), 2.87 m (2H, H1, H4), 2.38 s
(3H, CH3), 1.32 d (1H, H7s, 2J7s,7a 10.0 Hz), 0.98 d (1H,
H7a). Found, %: N 8.10. C16H16N2O5S. Calculated, %:
N 8.05.
N-(pBromophenylsulfonylamino)-exo-2,3-epoxy-
bicyclo[2.2.1]heptane-endo-5,endo-6- dicarboximide
(IXb) was obtained by oxidation of compound IVb. Yield
80.6%, mp 182–184°C, Rf 0.91 (ether–2-propanol, 20:1).
IR spectrum, cm–1: 3245, 1725, 1570, 1470, 1360, 1170,
860. Found, %: N 6.79. C15H13BrN2O5S. Calculated, %:
N 6.78.
N-(2-Hydroxy-3-carbazolylpropylamino)bicyclo-
[2.2.1]hept-2-ene-endo-5,endo-6-dicarboxamide
(VIIIa). To a solution of 0.50 g (2.8 mmol) of aminoimide
III in 2-propanol was added at stirring 0.62 g (2.8 mmol)
of 2,3-epoxypropylcarbazole. The stirring was continued
till reaction completion (TLC monitoring). The solvent
was removed, the residue was recrystallized from
2-propanol. Yield 66.4%, mp 104–106°C, Rf 0.21 (ether).
IR spectrum, cm–1: 3360, 3240, 3070, 1780, 1720, 1615,
1470, 1345, 1230, 733. Found, %: N 10.39. C24H23N3O3.
Calculated, %: N 10.47.
N-(p-Nitrobenzoylamino)-exo-2,3-epoxybicyclo-
[2.2.1]heptane-endo-5,endo-6-dicarboximide (IXc)
was obtained by oxidation of compound Va Yield 79.5%,
mp 280°C (decomp.), Rf 0.74 (ether–2-propanol, 20:1).
IR spectrum, cm–1: 3225, 1730, 1680, 1610, 1600, 1540,
1
N-(2-Hydroxycyclohexylamino)bicyclo[2.2.1]-
hept-2-ene-endo-5,endo-6-dicarboximide (VIIIb. To
a solution of 0.50 g (2.8 mmol) of aminoimide III in 5 ml
of ethyl acetate was added at stirring 0.27 g (0.28 ml,
2.8 mmol) 1,2-epoxycyclohexane and 1–2 drops of
2-propanol as a catalyst. The stirring was continued till
reaction completion (TLC monitoring). The solvent was
removed, the residue was recrystallized from 2-propanol
Yield 63.8%, mp 129–131°C, Rf 0.14 (ether). IR spec-
trum, cm–1: 3355, 3240, 3060, 1780, 1725, 1620, 1420,
1275, 1200, 855. H NMR spectrum, δ, ppm: 11.46 s
(1H, NH), 8.37 d (2H, Harom), 8.12 d (2H, Harom), 3.43 m
(2H, H2, H3), 3.32 m (2H, H5, H6), 3.19 m (2H, H1, H4),
1.40 d (1H, H7s, J7s,7a 9.6 Hz), 1.08 d (1H, H7a). Found,
%: N 12.20. C16H13N3O6. Calculated, %: N 12.24.
N-(o-Chlorobenzoylamino)-exo-2,3-epoxybi-
cyclo[2.2.1]heptane-endo-5,endo-6-dicarb-oximide
(IXd) was obtained by oxidation of compound Vb. Yield
83.3%, mp 128–130°C, Rf 0.52 (ether–2-propanol, 20:1).
IR spectrum, cm–1: 3450, 1735, 1710, 1670, 1540, 1265,
1160, 855. Found, %: N 8.50. C16H13ClN2O4. Calculated,
%: N 8.42.
1
1350, 1225, 1145, 735. H NMR spectrum, δ, ppm:
7.35 s (1H, OH), 6.99 t (1H, NH), 5.96 m (2H, H2, H3),
4.57 m (1H, CH–OH), 4.55 m (CH–NH), 3.50–3.00 m
(8H, H cyclohexane), 3.30 m (2H, H1, H4), 3.20 m (2H,
H5, H6), 1.49 m (2H, H7s, H7a). Found, %: N 10.23.
C15H20N2O3. Calculated, %: N 10.14.
N-(m-Tolylureido)-exo-2,3-epoxybicyclo[2.2.1]-
heptane-endo-5,endo-6-dicarboximide (IXe) was
obtained by oxidation of urea VIa. Yield 30%, mp 138–
142°C (2-propanol–water), Rf 0.63 (ether–2-propanol,
20:1). IR spectrum, cm–1: 3380, 3280, 1540, 1315, 1170,
1110, 830. Found, %: N 12.60. C17H17N3O4. Calculated,
%: N 12.84.
Epoxy derivatives IXa–f. To a solution of 10 mmol
of an appropriate unsaturated compound in 15 ml of 98%
formic acid was added at room temperature with stirring
1.36 g(1.18 ml, 20 mmol) of 50% water solution of hydro-
gen peroxide; the temperature was raised to 30–35°C,
and the stirring was continued till reaction completion
(TLC monitoring). On removing the formic acid the solid
residue was washed with saturated sodium carbonate
solution, the reaction product was dried in air, and
recrystallized from a mixture of 2-propanol with water.
N-(p-Toluenesulfonylureido)-exo-2,3-epoxy-
bicyclo[2.2.1]heptane-endo-5,endo-6-dicarboximide
(IXf) was obtained by oxidation of compound VIb. Yield
45%, mp 139–140°C (2-propanol–water), Rf 0.79 (ether–
2-propanol, 20:1). IR spectrum, cm–1: 3520, 3340, 1730,
1620, 1570, 1500, 1200, 855. Found, %: N 10.70.
C17H17N3O6S. Calculated, %: N 10.74.
N-(p-Toluenesulfonylamino)-exo-2,3-epoxybi-
cyclo[2.2.1]heptane-endo-5,endo-6-dicarboximide
(IXa) was obtained by oxidation of compound IVa with a
85.9% yield, mp 203–205°C, Rf 0.78 (ether–2-propanol,
5-p-Nitrophenyl-10-amino-3,4,5,10-tetraaza-
tricyclo[5.5.1.02,6exo.08,12endo]tridecene-3-ene-9,11-
dione (Xa) was obtained by heating at reflux 0.45
RUSSIAN JOURNALOF ORGANIC CHEMISTRY Vol. 41 No. 8 2005

KAS’YAN et al.
1130
Rerum. Nature. Univ. Com. Chim., 1968, 12, 253; Japan
Patent 59-122465, 1984; Ref. Zh. Khim., 1985, 15O39P;
Koval, I., Sulfur Reports, 1993, vol. 14, p. 149.
4. Krishchik, O.V., Tarabara, I.N., Kas’yan, A.O., Shishki-
na, S.V., Shishkin, O.V., Isaev,A.K., and Kas’yan, L.I., Zh.
Org. Khim., 2004, vol. 40, p. 1188.
5. Japan Patent 48-2552, (1972); Ref. Zh. Khim., 1973, 23N365P.
6. Csende, F. and Czabo, Z., Synth. Commun., 1993, vol. 23,
p. 2957.
7. Augustin, M. and Reinemann, P., Z. Chem., 1972, vol. 12,
p. 101.
8. Augustin, M. and Reinemann, P., Z. Chem., 1973, vol. 13,
p. 61.
(2.5 mmol) of aminoimide III and 0.41 g (2.5 mmol) of
p-nitrophenyl azide in 5 ml of chloroform till completion
of the reaction (TLC monitoring). Then the solvent was
removed, and the residue was recrystallized from
2-propanol. Yield 84.5%, mp 230–232°C (decomp.), Rf
0.18 (ether–2-propanol, 20:1). IR spectrum, cm–1: 3360,
3300, 1790, 1730, 1610, 1520, 1345, 1220, 860. 1H NMR
spectrum, δ, ppm: 8.34 d (2H, Harom), 7.33 d (2H, Harom),
3
4.95 s (2H, NH2) 4.63 d (1H, H6, J6,2 9.0 Hz), 3.84 d
3
3
(1H, H2, J2,6 8.7 Hz), 3.35 m (1H, H8, J8,12 9.6 Hz),
3.30 m (1H, H12, J12,8 9.3 Hz), 3.15 m (1H, H7, J7,8
3
3
4.2 Hz), 3.04 m (1H, H1, 3J1,12 3.9 Hz), 1.60 d (1H, H13s
,
2J13s,13a 11.1 Hz), 1.10 d (1H, H13a). Found, %: N 24.63.
9. Auksi, H. and Yates, P., Can. J. Chem., 1981, vol. 59,
p. 2510.
C15H14N6O4. Calculated, %: N 24.56.
5-p-Bromophenyl-10-amino-3,4,5,10-tetraaza-
tricyclo[5.5.1.02,6exo.08,12endotridecene-3-ene-9,11-
dione (Xb) was obtained by the above described
procedure from compound III. Yield 55.6%, mp 216–
218°C (calc.), Rf 0.54 (ether–2-propanol, 20:1). IR
spectrum, cm–1: 3480, 3340, 1790, 1730, 1605, 1505, 1420,
1380, 1220, 830. Found, %: N 18.70. C15H14BrN5O2.
Calculated, %: N 18.62.
5-p-Bromophenyl-10-(p-toluenesulfonylamido)-
3,4,5,10-tetraazatricyclo[5.5.1.02,6exo.08,12endo]-
tridecene-3-ene-9,11-dione (Xc) was obtained by
heating at reflux 0.83 g (2.5 mmol) of sulfonamide IVa
and 0.50 g (2.5 mmol) of p-bromophenyl azide in 5 ml of
chloroform; the reaction progress was monitored by TLC.
On completion of the reaction the solvent was removed,
and the residue was recrystallized from 2-propanol. Yield
67.0%, mp 205–207°C (decomp.), Rf 0.87 (ether–
2-propanol, 20:1). IR spectrum, cm–1: 3330, 1710, 1590,
1500, 1485, 1370, 1215, 1140, 845. Found, %: N 13.15.
C22H20BrN5O4S. Calculated, %: N 13.21.
10. Hedaya, E. and Hinman, R.L., J. Org. Chem., 1966, vol. 31,
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12. Nakanisi, K., Infrakrasnye spektry i stroenie organi-
cheskikh soedinenii (IR Spectra and Structure of Organic
Compounds), Moscow: Mir, 1965, 209 p.; Bellamy, L.J., The
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