Amides containing two norbornene fragments. Synthesis and chemical transformations

Article abstract of DOI:10.1007/s11178-005-0034-0

Reactions of stereochemically pure bicyclo[2.2.1]hept-5-en-exo- and endo-2-ylmethylamines with bicyclo[2.2.1]hept-2-ene-5-carbonyl chlorides gave the corresponding carboxamides having two norbornene fragments. Their conformations and steric strains were studied by the MM2 molecular mechanics method, and electron density distribution in their molecules was determined by PM3 quantum-chemical calculations. The results of calculation of the energy of activation for epoxidation of the dienes in the gas phase and in solution (COSMO) showed that chemoselective oxidation of only one double bond therein is impossible. The corresponding diepoxy derivatives were synthesized by oxidation of the dienes with peroxyacetic acid; the oxidation of amides with endo orientation of the carbonyl group was accompanied by heterocyclization with formation of exo-2-hydroxy-4-oxatricyclo[4.2.1.0^3,7]nonan-5-one. Reduction of the amides and their epoxy derivatives with lithium tetrahydridoaluminate afforded the corresponding secondary amines possessing two cage-like fragments; the reduction products were functionalized at the nitrogen atom by treatment with p-nitrobenzenesulfonyl chloride and p-toluenesulfonyl isocyanate. The structure of the prepared compounds was confirmed by the IR and ¹H and ¹³C NMR spectra.

Full text of DOI:10.1007/s11178-005-0034-0

Russian Journal of Organic Chemistry, Vol. 40, No. 10, 2004, pp. 1415–1426. Translated from Zhurnal Organicheskoi Khimii, Vol. 40, No. 10, 2004,
pp. 1467–1478.
Original Russian Text Copyright © 2004 by L. Kas’yan, Isaev, A. Kas’yan, Golodaeva, Karpenko, Tarabara.
Amides Containing Two Norbornene Fragments.
Synthesis and Chemical Transformations
L. I. Kas’yan1, A. K. Isaev1, A. O. Kas’yan2, E. A. Golodaeva1,
D. V. Karpenko1, and I. N. Tarabara1
1 Dnepropetrovsk National University, per. Nauchnyi 13, Dnepropetrovsk, 49050 Ukraine
2 Institut für organische Chemie, Rheinisch–Westfälische technische Hochschule, Aachen, Germany
Received July 22, 2003
Abstract—Reactions of stereochemically pure bicyclo[2.2.1]hept-5-en-exo- and endo-2-ylmethylamines with
bicyclo[2.2.1]hept-2-ene-5-carbonyl chlorides gave the corresponding carboxamides having two norbornene
fragments. Their conformations and steric strains were studied by the MM2 molecular mechanics method, and
electron density distribution in their molecules was determined by PM3 quantum-chemical calculations. The
results of calculation of the energy of activation for epoxidation of the dienes in the gas phase and in solution
(COSMO) showed that chemoselective oxidation of only one double bond therein is impossible. The
corresponding diepoxy derivatives were synthesized by oxidation of the dienes with peroxyacetic acid; the
oxidation of amides with endo orientation of the carbonyl group was accompanied by heterocyclization with
formation of exo-2-hydroxy-4-oxatricyclo[4.2.1.03,7]nonan-5-one. Reduction of the amides and their epoxy
derivatives with lithium tetrahydridoaluminate afforded the corresponding secondary amines possessing two
cage-like fragments; the reduction products were functionalized at the nitrogen atom by treatment with
p-nitrobenzenesulfonyl chloride and p-toluenesulfonyl isocyanate. The structure of the prepared compounds
was confirmed by the IR and 1H and 13C NMR spectra.
Among all bi- and polycyclic compounds, amides
of the norbornene and norbornane series have been
studied most thoroughly [1]. Despite vast experimental
data accumulated in this field, a considerable part of
them was obtained by studying mixtures of stereoiso-
meric compounds. Amides having cage-like fragments
are synthesized from both norbornenecarboxylic acids,
in particular compounds Ia and Ib and their saturated
analogs, and cage-like amines, e.g., IIa and IIb.
viously [2], and their reduction [3], hydrolysis [4], and
epoxidation with peroxy acids [5] were studied.
N-Acyl derivatives of bicyclic amines IIa and IIb were
synthesized by the action of acyl chlorides [6, 7] and
anhydrides [8]; in addition, their stereochemical
behavior [9], alkylation [10], reduction [6, 7], and
epoxidation [9] were reported.
Various amides were tested for biological activity
[1]; unsaturated amides in which the amino group is
attached directly to the bicyclic skeleton were studied
most extensively. Compounds IIIa (n = 1, 2; R1, R2 =
H, lower alkyl groups; R1R2N = 1-pyrrolidinyl) and
their analogs with a double bond in the bicyclic
skeleton or substituents in positions 1 and 7 were
found to exhibit antiarrhythmic activity [11]. Nor-
bornane derivatives IIIb showed no antiarrhythmic
acitivity but exhibited pronounced hypnotic properties
[12]. Antiarrhythmic, hypoglycemic, and hypotensive
activity was found for amide IIIc possessing two
bicyclic fragments [13].
COOH
COOH
Ia
Ib
CH2NH2
CH2NH2
IIa
IIb
N-Aryl- and N-alkyl-substituted amides derived
from bicyclic acids Ia and Ib were described pre-
Unlike N-acyl derivatives of cage-like amines, nor-
bornene- and norbornanecarboxamides exhibit anticon-
1070-4280/04/4010-1415 © 2004 MAIK “Nauka/Interperiodica”

KASYAN et al.
1416
vulsant effect [1]. Comparison of biological activity of
exo and endo isomers of amides by pentetrazole test
revealed a persistent favorable therapeutic index for
the endo stereoisomers which turned out to be less
active [14]. Taking into account high biological
activity of both groups of cage-like amides and indis-
putable importance of the stereochemical factor for
biological activity, we have synthesized amides Va–Vd
from stereochemically pure bicyclo[2.2.1]hept-5-ene-
exo- and -endo-2-carboxylic acids Ia and Ib and
bicyclo[2.2.1]hept-5-en-exo- and -endo-2-ylmethyl-
amines IIa and IIb.
[17]. Cross reactions of stereoisomeric carbonyl
chlorides IVa and IVb with amines IIa and IIb were
carried out in chloroform in the presence of triethyl-
amine under standard conditions for preparation of
amides [6, 7, 9].
The structure and conformational behavior of
amides Va–Vd were studied by the MM2 molecular
mechanics method [18]. Molecules Va–Vd contain
conformationally labile groups which undergo steric
effect of two bulky rigid bicyclic fragments. The
optimal conformations of molecules Va–Vd were
determined by analysis of the total steric energy upon
variation of the torsion angle C4C5C8N (for atom num-
bering, see structure Va) via rotation of the amino-
methyl fragment about the C5–C8 bond. In addition,
rotation about the NH–CO and C(O)–C5 bonds was
examined. The results of MM2 calculations revealed
syn orientation of the two methylene bridges in mole-
cules Vb and Vd (with endo-carbonyl group) and anti
orientation of the CH2 bridges in isomers Va and Vc.
NHCOCH2NR2
NHCO(CH2)nNR1R2
IIIa
IIIb
COMe
N
The calculated total steric energies of amides Va–
Vd were 205.86, 199.00, 199.81, and 198.58 kJ/mol,
respectively, and the corresponding strain energies
were 191.3, 184.2, 185.1, and 183.8 kJ/mol. It is seen
that the strain energy slightly decreases in the series
Va > Vc ≈ Vb > Vd; this means insignificant energy
preference of the amides with endo orientation of the
carbonyl group, presumably due to smaller contribu-
tion of the torsion strain to the total strain energy of
amides Vb and Vd. The main contribution is that
originating from distortion of bond angles (143.59–
148.56 kJ/mol).
IIIc
Initial acids Ia and Ib and amines IIa and IIb were
prepared from the corresponding individual stereoiso-
mers of bicyclo[2.2.1]hept-5-ene-2-carbonitrile which
is a Diels–Alder adduct of cyclopentadiene and acrylo-
nitrile. The stereoisomers were separated by fractional
distillation [15]. Amines IIa and IIb were synthesized
by reduction of bicyclic nitriles with lithium tetra-
hydridoaluminate [16], and mild hydrolysis of the
same nitriles afforded acids Ia and Ib. For the syn-
thesis of acyl chlorides IVa and IVb we selected con-
ditions which prevented isomerization of the products
The IR spectra of amides Va–Vd contain absorption
bands in the regions 1661–1628 (νC=O, amide I) and
1570–1553 cm–1 (δN–H, amide II) [19]. Stretching
vibrations of the N–H bond give rise to absorption at
3278–3267 cm–1, and unsaturated bicyclic fragments
are characterized by absorption bands at 3060–3030
(νC–H) and 720–705 cm–1 (δC–H). The band corre-
sponding to stretching vibrations of the double C=C
bond is overlapped by weak bands belonging to
bending vibrations of the N–H bond; The νC=C fre-
quency changes to 1575–1550 cm–1 due to steric strain
in the norbornene fragment [20].
7
7
O
O
1
1
6
2
6
2
8
8
4
4
N
H
N
3
5
5
3
H
Va
Vb
The different steric structures of amides Va–Vd are
reflected in their H NMR spectra (Table 1). For each
O
O
1
compound, signals from protons in the acid and amine
moieties are given. The spectral patterns are fairly
complex, for the chemical shifts of the corresponding
protons in the two norbornene fragments are very
N
H
N
H
Vc
Vd
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 10 2004

AMIDES CONTAINING TWO NORBORNENE FRAGMENTS.
Table 1. 1H NMR spectra of compounds IIa, IIb, Va–Vd, VIa, and VIb
1417
Chemical shifts δ, ppm, and coupling constants J, Hz
syn-7-H,
Comp.
no.
Fragment
NH2
(NH)
1-H, 4-H 2-H, 3-H 5-H
exo-6-H
endo-6-H
8-HA, 8-HB
2.65
anti-7-H
Amine 2.73, 2.59 5.96, 6.03 1.35
1.14
1.04
1.14, 1.22
1.13
IIa
IIb
Va
3
3J2,3 = 6.0,
3J2,1 = 2.8,
3J3,4 = 2.8
2Jexo-6,endo-6 = 11.3, Jendo-6,5 = 3.6
3Jexo-6,1 = 8.0
Amine 2.81, 2.72 5.86, 6.07 2.03
1.75
0.42
1.37, 1.18
2.37, 2.29 1.21
3
2
2
3J2,3 = 5.8,
3J2,1 = 2.8,
3J3,4 = 3.0
2Jexo-6,endo-6 = 11.4, Jendo-6,5 = 4.1, Jsyn-7,anti-7 = 7.9 J8A,8B = 12.2,
3Jexo-6,5 = 9.2,
3Jexo-6,1 = 3.9
4Jendo-6,syn-7 = 2.6
3J8A,5 = 7.3,
3J8B,5 = 8.2
Amine 2.84, 2.61
6.07
1.93
1.36
1.17
1.36
3.30
5.62
5.56
2Jexo-6,endo-6 = 12.0,
3Jexo-6,5 = 7.8
Acid
2.92
6.15
6.14
2.00
1.93
1.55
1.27
1.15
1.35
1.36, 1.73
–
3.25
–
2Jexo-6,endo-6 = 12.0
2Jsyn-7,anti-7 = 8.1
Amine 2.92, 2.83
1.35
1.23, 1.44
Vb
Vc
2Jexo-6,endo-6 = 12.0
2Jsyn-7,anti-7 = 8.5
Acid
2.92, 2.58 6.24, 5.96 1.98
1.54
1.35, 1.74
2Jexo-6,endo-6 = 11.8,
3Jexo-6,5 = 8.6,
3Jexo-6,1 = 4.3
2Jsyn-7,anti-7 = 8.9
Amine
Acid
2.81
2.88
6.16, 5.96 2.20
3J2,3 = 3.0,
1.84
0.54
1.42, 1.27
2.95, 3.03 5.61
3
2
2
2Jexo-6,endo-6 = 12.6, Jendo-6,5 = 3.0, Jsyn-7,anti-7 = 8.1 J8A,8B = 13.5,
3J2,1 = 2.4,
3Jexo-6,5 = 9.0,
3Jexo-6,1 = 3.9
4Jendo-6,syn-7 = 2.2
3J8A,5 = 7.2,
3J8B,5 = 5.7
3J3,4 = 2.7
6.14, 6.11 1.99
1.89
1.33
1.30, 1.69
–
2Jsyn-7,anti-7 = 8.3
Amine 2.84, 2.74 6.09, 5.91 2.15
1.78
0.49
1.08
1.66, 1.24
3.17
–
5.55
Vd
2Jexo-6,endo-6 = 11.3
Acid
Acid
3.07, 2.85 6.17, 5.87 1.90
1.90
1.28, 1.17
2Jexo-6,endo-6 = 11.5,
3Jexo-6,5 = 3.9
2Jsyn-7,anti-7 = 8.2
2.88, 2.85 6.06, 6.01 1.95
3J2,3 = 5.5,
1.27
1.88
1.32, 1.68
a4.39, 4.34a 5.79
a4.43, 4.35a 6.02
VIa
VIb
2Jexo-6,endo-6 = 11.1, Jendo-6,5 = 3.7, Jsyn-7,anti-7 = 8.4
3
2
3J2,1 = 3.0,
3Jexo-6,5 = 8.5,
3Jexo-6,1 = 2.5
4Jendo-6,syn-7 = 3.7
3J3,4 = 3.0
Acid
2.92, 3.16 6.23, 5.98 2.91
1.93
1.41
1.46, 1.29
2Jexo-6,endo-6 = 12.8, Jendo-6,5 = 4.0, Jsyn-7,anti-7 = 7.9
3
2
3Jexo-6,5 = 9.4,
3Jexo-6,1 = 3.8
4Jendo-6,syn-7 = 2.7
a
Benzyl CH2 group.
1
1
similar. The signals were assigned using the H NMR
data for initial amines IIa and IIb. Two-dimensional
1H–{1H} NMR spectra were recorded for endo isomer
IIb and related N-arylamides [6, 7]. As models of
the carbonyl-containing fragments we used specially
synthesized amides VIa and VIb for which two-
dimensional H–{1H} and 13C–{1H} NMR spectra
were recorded. As follows from the data in Table 1, the
amides with exo-oriented substituents in both amine
and acid fragment are characterized by more similar
chemical shifts of protons at the double bonds (2-H
and 3-H), while endo orientation of the substituents
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 10 2004

KASYAN et al.
1418
molecular orbitals (OMO) of amides Va–Vd and
O
contributions of atomic orbitals to the OMO using
the PM3 semiempirical method. The results are sum-
marized in Table 2. It is seen that in all cases the
HOMO is localized mainly on the amide nitrogen and
oxygen atoms. The olefinic C2 and C3 atoms contribute
mainly to the II-OMO and III-OMO whose energies
are very similar. The small contribution of these atoms
in the acid fragment of Vd is explained by distribution
of the corresponding atomic orbitals over IV-OMO–
VII-OMO. According to the obtained results, the reac-
tivities of the double bonds do not differ appreciably.
N
H
N
H
O
VIa
VIb
differentiates these protons, the greater difference
being observed for protons in the acid fragment. The
isomers can be identified by the position of the 5-H
signal: the exo-5-H protons (endo isomers) resonate in
a weaker field (∆δ ≈ 0.5 ppm) than endo-5-H (exo
isomers). This difference originates from magnetically
anisotropic effect of the carbon–carbon bonds in the
bicyclic moieties. endo Orientation of the amine frag-
ment unambiguously follows from the position and
multiplicity of the endo-6-H signal which appears in
the spectrum of amide Vc as an octet at δ 0.54 ppm
Table 2 also contains the calculated (COSMO [23])
energies of activation (∆H≠) for epoxidation of amides
Va–Vd at both double bonds in the gas phase and in
solution. The activation barriers were calculated rela-
tive to the sum of the enthalpies of formation of the
initial reactants; vibration frequencies were calculated
for each stationary point. Transition states were charac-
terized by a single imaginary frequency, while fre-
quencies for the initial reactants and products (minima
on the potential energy surface) were positive. The
structures of the transition states are similar to those
determined previously for epoxidation of substituted
norbornenes [24]. As follows from the data in Table 2,
the energies of activation for reactions at both olefinic
fragments are similar; therefore, their chemoselective
transformation seems to be impossible. Taking into
account these results, epoxidation of dienes Va–Vd
was performed with excess oxidant to obtain com-
pounds containing two epoxy rings. The reactions were
carried out with peroxyacetic acid which was prepared
in situ from acetic anhydride and 70% hydrogen
peroxide; the amide–acetic anhydride–hydrogen per-
[2Jendo-6,exo-6 = 12.6, Jendo-6,5 = 3.0, 4Jendo-6,syn-7 = 2.2 Hz
3
(W-coupling)]; an analogous pattern is observed in
the spectra of IIb and Vd. Undoubtedly, the upfield
position of the above signal is determined by mag-
netically anisotropic effect on the C5–C8 bond in the
endo-amine and its derivatives. No such effect is
observed for the carbonyl-containing fragments of
1
the amides (cf. H NMR spectral data for compounds
Vb and Vd).
Amides Va–Vd are polyfunctional compounds in
which the double bonds are influenced by electron-
acceptor carbonyl group and weakly electron-donor
aminomethyl group. In order to elucidate the pos-
sibility for chemoselective epoxidation of only one
of the double bonds we performed [21] quantum-
chemical calculations of the energies of occupied
Table 2. Calculated energies of occupied molecular orbitals (EOMO, eV), contributions of particular atomic orbitals to OMOs,
and energies of activation (∆H≠, ∆H≠solv, eV) for epoxidation of amides Va–Vd
Comp. no. Fragment
EHOMO, eV
EOMO, eV
Contributions to OMO, %
∆H≠
∆H≠solv
Amine
–9.53
III-OMO, –10.04
II-OMO, –9.97
II-OMO, –9.94
C2, 39.73; C3, 40.84
C2, 41.15; C3, 40.66
14.71
15.83
14.42
11.30
11.42
11.35
Va
Acid
Amine
–9.55
II, C2, 32.27; C3, 32.34
Vb
III, C2, 7.03; C3, 7.26
Acid
III-OMO, –9.99
II: C2, 8.21; S3, 8.38
15.74
12.39
III: C2, 33.13; S3, 33.13
Amine
–9.54
–9.41
II-OMO, –9.91
III-OMO, –10.05
III-OMO, –9.95
II-OMO, –9.86
C2, 39.82; C3, 40.11
C2, 43.37; C3, 40.93
C2, 40.11; C3, 40.16
C2, 3.93; C3, 3.27
14.79
14.58
14.71
14.22
10.69
11.14
11.38
11.75
Vc
Acid
Amine
Vd
Acid
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 10 2004

AMIDES CONTAINING TWO NORBORNENE FRAGMENTS.
1419
nenes IXa (R = H, alkyl, benzyl, aryl) led to formation
of lactone VIII as the only product [5], while acyl
derivatives IXb (R = alkyl, aryl) of amine IIb were
converted exclusively into epoxides IXc under the
same conditions. Heterocyclization to azabrendane
structures like IXd occurred only after subsequent
reduction of epoxy derivatives IXc with lithium tetra-
hydridoaluminate [9].
oxide molar ratio was 1:3:3, and chloroform was used
as solvent.
Unlike the data of [5], the only or major oxidation
products were bis-epoxy derivatives VIIa–VIId. Com-
pounds VIIa and VIIc were isolated as crystalline
substances, and their isomers VIIb and VIId were oily
liquids. The latter were subjected to chromatographic
purification on silica gel; as a result, from amide Vb
we obtained 60.5% of epoxide VIIb and 10% of
lactone VIII, and from amide Vd, 57.4% of epoxide
HO
1
VIId and 7.3% of lactone VIII. The H NMR spectra
R'CO3H
VIII
of the crude products obtained by oxidation of amides
Vb and Vd also showed the presence of lactone VIII.
CONHR
O
R
N
H
7
7
IXa
O
O
O
1
1
O
2
2
6
6
O
O
4
4
N
N
3
5
5
3
H
H
R'CO3H
CH2NHCOR
IXb
CH2NHCOR
O
VIIa
VIIb
IXc
O
O
HO
LiAlH4
O
O
O
N
N
N
RCH2
H
H
IXd
O
Amides Va–Vd are especially interesting from the
viewpoint of their oxidation with peroxy acids, for
their molecules include both carbamoyl and acyl-
aminomethyl groups which are oriented differently
with respect to the conformationally rigid bicyclic
fragments. On the basis of published data, we expected
formation of diepoxy derivatives from amides Va and
Vc and of lactone VIII from amides Vb and Vd. The
formation of bis-epoxides as major products in the
oxidation of amides Vb and Vd indicates strong steric
hindrances to location of one cage-like fragment at the
rear (endo) area of the other; such arrangement is
necessary for intramolecular attack by the nucleophilic
carbonyl oxygen atom at the electrophilic carbon atom
of the activated epoxy ring [25].
VIIc
VIId
HO
O
O
VIII
In the recent years, numerous examples of forma-
tion of heterocyclic systems from epoxy derivatives
attract researchers’ attention [22, 23]. It is known that
orientation of substituents in the bicyclic skeleton is
the main factor determining the possibility for hetero-
cyclization in reactions of substituted norbornenes with
peroxy acids. Compounds having exo-oriented substit-
uents (such as carboxy, methoxycarbonyl, carbamoyl,
acylamino, sulfonylamino, and other groups) react
with peroxy acids to afford only the corresponding
epoxy derivatives, while their endo isomers could give
rise to heterocyclization, depending on the substituent
nature. Epoxidation of carbamoyl-substituted norbor-
In the IR spectra of the oxidation products, the most
characteristic are absorption bands in the region 850–
840 cm–1, which belong to stretching vibrations of
the C–O bonds. The absorption typical of carboxamide
groups is retained, whereas bands at 730–700 cm–1
(δC–H) due to olefinic fragments in substituted nor-
bornenes disappear from the spectra.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 10 2004

KASYAN et al.
1420
Table 3. 1H NMR spectra of compounds VIIa, VIIc, Xa, and Xb obtained by epoxidation of the corresponding amides
Chemical shifts δ, ppm, and coupling constants J, Hz
Comp.
no.
Fragment
syn-7-H,
anti-7-H
NH2
(NH)
1-H, 4-H 2-H, 3-H 5-H
Amine 2.57, 2.25 3.00–3.10 1.60
exo-6-H
endo-6-H
8-HA, 8-HB
3.00–3.10
1.36
1.05
1.25, 0.81
5.72
VIIa
2Jexo-6,endo-6 = 11.5,
3Jexo-6,5 = 8.4,
3Jexo-6,1 = 2.4
2Jsyn-7,anti-7 = 10.2
Acid
2.47, 2.41 3.00–3.10 2.08
1.64
1.20
0.81
1.39, 1.18
–
–
2Jexo-6,endo-6 = 12.4
2Jsyn-7,anti-7 = 8.3
Amine 2.51, 2.48 3.28, 3.09 1.50
1.73
1.37, 0.76
3.20–3.32
5.59
VIIc
3J2,3 = 3.0
2Jexo-6,endo-6 = 12.7, Jendo-6,5 = 4.9, Jsyn-7,anti-7 = 10.0 J8A,8B = 13.6,
3
2
2
3Jexo-6,5 = 10.7, 4Jendo-6,syn-7 = 2.3
3Jexo-6,1 = 4.3
3J8B,5 = 7.8
Acid
2.60, 2.40 3.14, 3.11 2.11
1.94
1.24
1.26, 1.18
–
–
2Jexo-6,endo-6 = 8.6
2Jsyn-7,anti-7 = 10.0
Amine 2.47, 2.36 3.09, 3.05 1.82
1.52
1.17
1.28, 0.88
3.37, 3.31
6.48
Xa
Xb
3
2
3J2,3 = 3.5
2Jexo-6,endo-6 = 12.6, Jendo-6,5 = 4.1 Jsyn-7,anti-7 = 10.4 2J8A,8B
=
3Jexo-6,5 = 8.4,
3Jexo-6,1 = 2.4
13.4,
3J8A,5 = 7.1,
3J8B,5 = 8.3
Amine 2.55, 2.51 3.22, 3.27 2.27
1.83
0.93
1.43, 0.82
3.57, 3.42
6.29
3J2,3 = 3.8
2Jexo-6,endo-6 = 12.5, Jendo-6,5 = 4.8, Jsyn-7,anti-7 = 9.9
2J8A,8B
=
3
2
3Jexo-6,5 = 9.9,
3Jexo-6,1 = 4.3
4Jendo-6,syn-7 = 2.7
13.7,
3J8A,5 = 9.0,
3J8B,5 = 7.6
The 1H NMR spectra of epoxy derivatives VIIa and
VIIc contained signals at δ 3.10–3.30 ppm (Table 3),
which are typical of epoxynorbornanes. The stereo-
chemistry of epoxidation (Alder’s exo-attack rule [26])
follows from the presence of a doublet signal in the
region δ 0.80–1.20 ppm, which belongs to the anti-7-H
proton. The latter is located directly above the oxirane
ring plane in the molecules of exo-epoxynorbornanes,
so that it appears in the area of anisotropic effect of
the oxirane ring. Compounds VIIa and VIIc differing
by the orientation of the amine fragments are charac-
terized by different chemical shifts of protons in those
fragments; the observed spectral patterns are consistent
with our previous data for N-acyl derivatives of stereo-
isomeric amines IIa and IIb [9]. These differences
include primarily resonances of protons in the oxirane
ring (2-H, 3-H), protons in the bridgehead positions
(1-H, 4-H), methylene protons in the substituent, and
proton on C6 [9, 27]. For comparison, Table 3 contains
O
O
N
H
NO2
1
the H NMR spectral parameters of stereoisomeric
Xa
epoxides Xa and Xb for which two-dimensional
spectra were also measured [7].
O
The 13C NMR spectra of compounds VIIa–VIIc
are given in Table 4. In particular, the carbonyl carbon
atoms resonate at δC 174–175 ppm, and signals from
carbon atoms involved in the oxirane ring appear at
δC 51–53 ppm. In most cases the chemical shifts of C2
and C3 are almost similar, and only the corresponding
signals from the amine fragment of VIIc differ by
2.8 ppm. The 13C signals were assigned on the basis of
the two-dimensional spectra of compounds Xa and Xb,
O
N
NO2
H
Xb
O
O
NMe2
XI
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 10 2004

AMIDES CONTAINING TWO NORBORNENE FRAGMENTS.
1421
N
H
N
H
XIIa
XIIb
O
O
O
N
H
N
H
O
XIIc
XIId
as well as of epoxy amide XI described in [28]; the
13C NMR spectrum of the latter was solved using the
selective double 13C–{H} resonance technique.
compounds XIIa and XIIb showed in the IR spectra
absorption bands at 3066 and 3068 cm–1 due to
stretching vibrations of the C–H bonds contiguous to
the strained double C=C bond; epoxy amines XIIc
and XIId were characterized by absorption at 855 and
860 cm–1 due to C–O stretching vibrations and at 3040
and 3035 cm–1 due to vibrations of the C–H bonds in
the three-membered ring [19].
The amide group in compounds Va and Vc can be
reduced to obtain previously unknown and difficultly
accessible amines XIIa and XIIb which possess two
norbornene fragments. The reduction of epoxy deriva-
tives VIIa and VIIc under analogous conditions was
strictly chemoselective; as a result, we obtained epoxy
amines XIIc and XIId in which the oxirane fragments
remained intact. The observed reaction path is typical
of epoxynorbornanes in neutral and alkaline media. It
indicates the crucial role of steric factor which hinders
intermolecular attack by bulky nucleophilic reagent on
the electrophilic oxirane carbon atoms from the rear
side of the bicyclic carbon skeleton (in keeping with
the known relations holding in bimolecular nucleo-
philic substitution mechanism [29]).
Amines XIIa–XIId were converted into the corre-
sponding hydrochlorides XIIIa–XIIId. In the IR spe-
ctra of XIIIa–XIIId we observed ammonium bands in
the region 2768–2740 cm–1 [νas(+NH2) and νs(+NH2)],
which were not overlapped by C–H stretching vibra-
tion bands [19]. The absorption patterns due to cyclic
fragments were almost the same as in the spectra of the
corresponding free bases.
We previously found that p-nitrobenzenesulfon-
amides derived from amines IIa and IIb exhibit a high
and versatile neurotropic activity [30]. Taking these
data into account, we synthesized sulfonamides XIVa–
XIVd by treatment of amines XIIa–XIId with equi-
The IR spectra of oily amines XIIa–XIId lack
absorption bands due to carboxamide fragment but
νNH bands are present at 3360–3310 cm–1. In addition,
Table 4. 13C NMR spectra of epoxy derivatives VIIa–VIIc and compounds Xa, Xb, and XI, δ, ppm
Compound
Fragment
C1, C4
C2, C3
C5
C6
C7
C8
C=O
no.
36.6, 42.2
36.9, 46.7
36.5, 43.4
36.9, 43.5
37.6, 44.7
28.2, 43.2
36.9, 39.7
38.2, 42.2
36.7, 40.1
51.2, 51.1
51.8, 51.7
51.7, 51.1
51.9, 51.3
52.8, 50.0
52.1, 52.1
51.6, 51.1
52.1, 49.9
51.5, 50.4
38.4
39.6
38.2
39.5
42.3
39.3
38.3
39.4
41.1
30.2
31.1
31.6
33.7
30.5
31.1
31.2
30.7
30.6
23.2
23.9
23.1
23.9
28.1
24.9
23.2
28.2
23.9
43.2
–
–
174.1
–
VIIa
Amine
Acid
Amine
Acid
43.2
–
VIIb
VIIc
174.3
–
Amine
Acid
41.8
–
175.1
–
Amine
Amine
Acid
43.9
42.7
–
Xa
Xb
XI
–
173.1
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 10 2004

KASYAN et al.
1422
p-O2NC6H4SO2Cl
Et2O, H2O, NaOH
N
H
N
SO2C6H4NO2-p
XIIa
XIVa
O
O
O
O
N
N
N
SO2C6H4NO2-p
XIVd
SO2C6H4NO2-p
SO2C6H4NO2-p
XIVb
XIVc
p-MeC6H4SO2NCO
C6H6
XIIb
N
CONHSO2C6H4Me-p
XV
1
molar amounts of p-nitrobenzenesulfonyl chloride and
sodium hydroxide in a two-phase system (water–di-
ethyl ether). Amine XIIb was also brought into reac-
tion with p-toluenesulfonyl isocyanate, which afforded
sulfonylurea XV.
signals in the H NMR spectrum of XIVd were
assigned by comparing with the spectra of epoxy
derivatives XIVc and XVIb. Quite demonstrative is
the position of signal from 5-H in different fragments
of XIVd: δ 1.65 and 2.15 ppm for the exo- and endo-
amine, respectively; also, a considerable difference in
the chemical shifts of exo-6-H is observed: δ 1.45 and
1.89 ppm, respectively. On the other hand, the pres-
ence in a single molecule of two bicyclic fragments
with different orientations of the substituents levels the
spectral differences which were proposed previously as
criteria for determination of steric structure of sulfon-
amides of the norbornene series [27].
In the IR spectra of sulfonamides XIVa–XIVd we
observed no N–H stretching vibration bands in the
region 3300–3200 cm–1, but absorption bands belong-
ing to vibrations of the sulfonyl (1338–1310 and 1168–
1165 cm–1) and nitro groups (1540–1530 and 1355–
1335 cm–1) were present. The amide fragment in sul-
fonylurea XV gave rise to amide absorption at 1640
(νC=O) and 1270 cm–1 (νC–N) and N–H absorption
1
at 3370 cm–1. Table 5 contains the H NMR spectral
EXPERIMENTAL
parameters of compounds XIVa, XIVc, and XIVd, as
well as of previously described sulfonamides XVIa
and XVIb [31].
The IR spectra were recorded on a Specord 75-IR
spectrometer in the range from 4000 to 400 cm–1 from
samples prepared as thin films or KBr pellets. The
1H NMR spectra were obtained on Varian VXR
(300 MHz) and Varian Gemini-BB (500 MHz) instru-
ments from solutions in chloroform-d or DMSO-d6
using TMS or HMDS as internal reference. The 13C
NMR spectra were measured on a Varian Gemini-BB
spectrometer at 100.7 MHz using COSY and NOESY
techniques. The progress of reactions was monitored,
and the purity of products was checked, by TLC on
Silufol UV-254 plates using diethyl ether as eluent;
spots were visualized by treatment with iodine vapor.
The elemental compositions were determined on
a Carlo Erba analyzer.
NHSO2C6H4NO2-p
XVIa
O
NHSO2C6H4NO2-p
XVIb
Unlike symmetric structures XIVa and XIVc, the
aminomethyl fragments in molecule XIVd differ by
orientation with respect to the bicyclic fragments. The
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 10 2004

AMIDES CONTAINING TWO NORBORNENE FRAGMENTS.
1423
Table 5. 1H NMR spectra of sulfonamides XIVa–XIVd and compounds XVIa and XVIb
Chemical shifts δ, ppm, and coupling constants J, Hz
Comp.
no.
Isomer
syn-7-H,
anti-7-H
1-H, 4-H 2-H, 3-H 5-H
exo-6-H
endo-6-H
8-HA, 8-HB
NH2, Harom
exo 2.79, 2.68 6.01 1.62
1.09
0.88
1.23, 1.32 3.32, 3.12 8.38 (2H, Harom),
XIVa
2Jsyn-7,anti-7
=
2J8A,8B
=
8.04 (2H, Harom)
10.0
12.9
exo 2.80, 2.61 5.97, 5.94 1.68
1.18
1.05
0.55
1.26, 1.36 3.10–3.21 8.40 (2H, Harom),
8.05 (2H, Harom
XIVb
)
2.79, 2.73 6.17, 6.04 2.33
1.80
1.22, 1.42 2.82–2.90
endo
3J2,3 = 6.0,
3J2,1 = 3.2,
3J3,4 = 3.0
2Jexo-6,endo-6 = 11.5
2Jsyn-7,anti-7
=
11.0
exo 2.45, 2.31 3.06, 3.02 1.65
3J2,3 = 3.8
1.47
1.05
1.08
1.08
1.01
1.24, 0.71 2.88, 2.83 7.92 (2H, Harom),
XIVc
XIVd
2Jexo-6,endo-6 = 13.4
2Jsyn-7,anti-7
=
2J8A,8B
=
7.65 (2H, Harom)
10.4
13.6
exo 2.45, 2.31 3.07, 3.01 1.65
3J2,3 = 3.8
1.45
1.20, 0.72 2.80–2.90 7.92 (2H, Harom),
2Jexo-6,endo-6 = 13.0
2Jsyn-7,anti-7
=
7.63 (2H, Harom)
10.6
endo 2.57, 2.44 3.12, 3.00 2.15
3J2,3 = 3.1
1.89
1.44, 0.72 3.00–3.10
2Jexo-6,endo-6 = 12.6
2Jsyn-7,anti-7
=
9.8
exo 2.74, 2.53 5.99, 5.94 1.45
3J2,3 = 5.6,
1.16
1.14, 1.28 3.02, 2.90 4.85 (1H, NH),
XVIa
XVIb
2Jexo-6,endo-6 = 11.7, Jendo-6,5 = 3.7 Jsyn-7,anti-7
=
2J8A,8B
=
8.31 (2H, Harom),
3
2
3J2,1 = 3.3,
3Jexo-6,5 = 7.8
10.0
12.6,
8.00 (2H, Harom
)
3J3,4 = 3.7
3J8A,5 = 5.9,
3J8B,5 = 6.3
exo 2.41, 2.27 3.04, 2.97 1.56
3J2,3 = 3.8
1.43
1.01
1.22, 0.67 2.85, 2.82 4.76 (1H, NH)
2Jexo-6,endo-6 = 12.4, Jendo-6,5 = 4.1, Jsyn-7,anti-7
=
8.31 (2H, Harom),
3
2
3Jexo-6,5 = 8.2, 3Jendo-6,syn-7 = 3.8
3Jexo-6,1 = 2.8
10.1
8.00 (2H, Harom)
Stereoisomeric bicyclo[2.2.1]hept-5-en-2-ylmethyl-
amines IIa and IIb were synthesized by the procedure
reported in [6]. Stereoisomeric acid chlorides IVa and
IVb were prepared from norbornenecarboxylic acids
Ia and Ib as described in [17].
mp 144–146°C, Rf 0.44. IR spectrum, ν, cm–1: 3271,
3057, 1640, 1553, 1415, 1241, 709. Found, %: N 5.79.
C16H21NO. Calculated, %: N 5.76.
Amides Vb–Vd were synthesized in a similar way.
N-(Bicyclo[2.2.1]hept-5-en-exo-2-ylmethyl)bi-
cyclo[2.2.1]hept-5-ene-endo-2-carboxamide (Vb).
Yield 3%, mp 146–148°C, Rf 0.65. IR spectrum, ν,
cm–1: 3278, 3049, 1661, 1564, 1421, 1240, 705. Found,
%: N 5.82. C16H21NO. Calculated, %: N 5.76.
N-(Bicyclo[2.2.1]hept-5-en-exo-2-ylmethyl)bicy-
clo[2.2.1]hept-5-ene-exo-2-carboxamide (Va). A so-
lution of 1.38 g (10 mmol) of bicyclo[2.2.1]hept-5-
ene-exo-2-carbonyl chloride (IVa) in chloroform was
added dropwise under stirring to a mixture of 1.23 g
(10 mmol) of amine IIa and 1.01 g (1.40 ml, 10 mmol)
of triethylamine in 20 ml of chloroform. The mixture
was stirred at room temperature until the reaction was
complete (TLC) and treated in succession with water,
20% hydrochloric acid, and water again. The organic
phase was separated, dried over calcined magnesium
sulfate, and evaporated, and the residue was recrys-
tallized from aqueous isopropyl alcohol. Yield 80%,
N-(Bicyclo[2.2.1]hept-5-en-endo-2-ylmethyl)bi-
cyclo[2.2.1]hept-5-ene-exo-2-carboxamide (Vc).
Yield 84%, mp 159–160°C, Rf 0.63. IR spectrum, ν,
cm–1: 3278, 3038, 1628, 1557, 1529, 1436, 1245, 713.
Found, %: N 5.67. C16H21NO. Calculated, %: N 5.76.
N-(Bicyclo[2.2.1]hept-5-en-endo-2-ylmethyl)-
bicyclo[2.2.1]hept-5-ene-endo-2-carboxamide (Vd).
Yield 80%, mp 137–139°C, Rf 0.44. IR spectrum, ν,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 10 2004

KASYAN et al.
1424
cm–1: 3267, 3031, 1632, 1520, 1427, 1240, 710. Found,
%: N 5.84. C16H21NO. Calculated, %: N 5.76.
culated, %: N 5.09. From the second fraction we
isolated 7% of lactone VIII, mp 157–158°C [5].
N-(exo-5,6-Epoxybicyclo[2.2.1]hept-exo-2-yl-
methyl)-exo-5,6-epoxybicyclo[2.2.1]heptane-exo-2-
carboxamide (VIIa). A 70% solution of hydrogen
peroxide, 0.51 g (0.44 ml, 15 mmol), was added drop-
wise under stirring to a mixture of 1.21 g (5 mmol) of
amide Va, 1.53 g (15 mmol) of acetic anhydride, and
0.15 g (2.5 mmol) of urea in 50 ml of chloroform.
The mixture was stirred at room temperature until
the reaction was complete (TLC) and neutralized with
a saturated solution of sodium hydrogen carbonate, the
organic phase was separated and dried over calcined
magnesium sulfate, the solvent was removed, and the
product was purified by recrystallization from aqueous
isopropyl alcohol. Yield 71%, mp 110–112°C. IR spec-
trum, ν, cm–1: 3282, 3020, 1645, 1550, 1373, 1310,
1082, 841. Found, %: N 5.12. C16H21NO3. Calculated,
%: N 5.09.
Bis(bicyclo[2.2.1]hept-5-en-exo-2-ylmethyl)-
amine (XIIa). A solution of 0.58 g (2.4 mmol) of
amide Va in 10 ml of anhydrous diethyl ether was
added dropwise under stirring to a suspension of 0.20 g
(5.2 mmol) of LiAlH4 in 10 ml of anhydrous diethyl
ether. The mixture was stirred for 6–8 h, maintaining it
slightly boiling, until the reaction was complete (TLC).
Excess LiAlH4 was decomposed with moist diethyl
ether and ice water, the precipitate was filtered off,
the organic phase was dried over calcined magnesium
sulfate, the solvent was removed, and the residue was
distilled under reduced pressure. Yield 89%, bp 88–
90°C (28 mm), Rf 0.06. IR spectrum, ν, cm–1: 3340,
3066, 1550, 712. Found, %: N 6.37. C16H23N. Calcu-
lated, %: N 6.11. Hydrochloride XIIIa: yield 85%,
mp 332–334°C. IR spectrum, ν, cm–1: 3180, 3070,
2768, 1555, 1450, 720.
N-(Bicyclo[2.2.1]hept-5-en-endo-2-ylmethyl)bi-
cyclo[2.2.1]hept-5-en-exo-2-ylmethylamine (XIIb)
was synthesized in a similar way. Yield 91%, bp 70–
71°C (32 mm), Rf 0.07. IR spectrum, ν, cm–1: 3310,
3068, 1552, 728, 708. Found, %: N 6.29. C16H23N.
Calculated, %: N 6.11. Hydrochloride XIIIb: yield
88%, mp 268–270°C. IR spectrum, ν, cm–1: 3170,
3060, 2740, 1450, 740, 710.
N-(exo-5,6-Epoxybicyclo[2.2.1]hept-exo-2-yl-
methyl)-exo-5,6-epoxybicyclo[2.2.1]heptane-endo-2-
carboxamide (VIIb) was synthesized in a similar way.
The crude product was subjected to column chroma-
tography on silica gel using diethyl ether as eluent. The
first fraction contained compound VIIb; yield 61%,
mp 123–124°C (from ethyl acetate–hexane), Rf 0.62.
IR spectrum, ν, cm–1: 3287, 3031, 1655, 1571, 1369,
1308, 1075, 852. Found, %: N 5.14. C16H21NO3. Cal-
culated, %: N 5.09. From the second fraction we
isolated exo-2-hydroxy-4-oxatricyclo[4.2.1.03,7]nonan-
5-one (VIII), yield 10%, mp 157–158°C, Rf 0.10.
IR spectrum, ν, cm–1: 3300, 1760. Compound VIII was
identical to an authentic sample described in [5].
Bis(exo-5,6-epoxybicyclo[2.2.1]hept-exo-2-yl-
methyl)amine (XIIc) was synthesized in a similar
way. Yield 70%, bp 92–94°C (20 mm), Rf 0.01. IR
spectrum, ν, cm–1: 3300, 3041, 1580, 855. Found, %:
N 5.53. C16H23NO2. Calculated, %: N 5.36. Hydro-
chloride XIIIc: yield 56%, mp 316–317°C. IR spec-
trum, ν, cm–1: 3170, 3038, 2750, 1550, 1450, 858.
N-(exo-5,6-Epoxybicyclo[2.2.1]hept-endo-2-yl-
methyl)-exo-5,6-epoxybicyclo[2.2.1]hept-exo-2-yl-
methylamine (XIId) was synthesized in a similar way.
Yield 87%, oily substance, Rf 0.01. IR spectrum, ν,
cm–1: 3360, 3035, 1581, 860. Found, %: N 5.51.
C16H23NO2. Calculated, %: N 5.36. Hydrochloride
XIIId: yield 77%, mp 235–237°C. IR spectrum, ν,
cm–1: 3150, 3035, 2740, 1550, 1450, 855.
N-(exo-5,6-Epoxybicyclo[2.2.1]hept-endo-2-yl-
methyl)-exo-5,6-epoxybicyclo[2.2.1]heptane-exo-2-
carboxamide (VIIc) was synthesized as described
above for VIIa. Yield 66%, mp 135–136°C (from
aqueous isopropyl alcohol). IR spectrum, ν, cm–1:
3306, 3032, 1641, 1546, 1284, 1120, 847. Found, %:
N 5.02. C16H21NO3. Calculated, %: N 5.09.
N-(exo-5,6-Epoxybicyclo[2.2.1]hept-endo-2-yl-
methyl)-exo-5,6-epoxybicyclo[2.2.1]heptane-endo-
2-carboxamide (VIId) was synthesized in a similar
way. The crude product was subjected to column
chromatography on silica gel using diethyl ether as
eluent. The first fraction contained compound VIId;
yield 57%, mp 169–171°C (from aqueous isopropyl
alcohol), Rf 0.65. IR spectrum, ν, cm–1: 3294, 3015,
1657, 1567, 840. Found, %: N 5.11. C16H21NO3. Cal-
N,N-Bis(bicyclo[2.2.1]hept-5-en-exo-2-ylmethyl)-
p-nitrobenzenesulfonamide (XIVa). A solution of
0.17 g (0.9 mmol) of p-nitrobenzenesulfonyl chloride
in 10 ml of diethyl ether was added dropwise under
stirring to a mixture of 0.20 g (0.87 mmol) of amine
XIIa, 0.035 g (0.03 ml, 0.87 mmol) of 20% aqueous
sodium hydroxide, and 15 ml of diethyl ether. The
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 10 2004

AMIDES CONTAINING TWO NORBORNENE FRAGMENTS.
1425
4. Malinovskii, M.S., Kas’yan, L.I., Ovsyanik, V.D., and
mixture was stirred at room temperature until the
reaction was complete (TLC), the organic layer was
separated and washed with calcined magnesium sul-
fate, the solvent was removed, and the product was
recrystallized from aqueous ethyl alcohol. Yield 65%,
mp 86–88°C, Rf 0.70. IR spectrum, ν, cm–1: 3060,
1605, 1536, 1352, 1318, 1168, 705. Found, %: N 6.70.
C22H26N2O4S. Calculated, %: N 6.76.
Sil’chenko, L.A., Zh. Org. Khim., 1973, vol. 9, p. 1306.
5. Malinovskii, M.S., Kas’yan, L.I., Ovsyanik, V.D.,
Samitov, Yu.Yu., Terent’ev, P.B., and Belikov, A.B.,
Zh. Org. Khim., 1974, vol. 10, p. 1173.
6. Kas’yan, A.O., Tarabara, I.N., Zlenko, E.T., Okovi-
tyi, S.I., and Kas’yan, L.I., Russ. J. Org. Chem., 1999,
vol. 35, p. 1018.
7. Kas’yan, A.O., Tarabara, I.N., Zlenko, E.T., and Kas’-
N-(Bicyclo[2.2.1]hept-5-en-endo-2-ylmethyl)-
N-(bicyclo[2.2.1]hept-5-en-exo-2-ylmethyl)-p-nitro-
benzenesulfonamide (XIVb) was synthesized in
a similar way. Yield 56%, mp 122–123°C, Rf 0.65.
IR spectrum, ν, cm–1: 3070, 1602, 1530, 1350, 1310,
1165, 750, 712. Found, %: N 6.81. C22H26N2O4S. Cal-
culated, %: N 6.76.
yan, L.I., Russ. J. Org. Chem., 2002, vol. 38, p. 165.
8. Kas’yan, A.O., Krishchik, O.V., Krasnovskaya, O.Yu.,
and Kas’yan, L.I., Russ. J. Org. Chem., 1998, vol. 34,
p. 1731.
9. Kasyan, L.I., Tarabara, I.N., Savel’eva, O.A., and
Kasyan, A.O., Heteroatom Chem., 2001, vol. 12, p. 119.
10. Kas’yan, L.I., Krasnovskaya, O.Yu., Tarabara, I.N., and
Kas’yan, A.O., Russ. J. Org. Chem., 1998, vol. 34,
p. 894.
N,N-Bis(exo-5,6-epoxybicyclo[2.2.1]hept-exo-2-
ylmethyl)-p-nitrobenzenesulfonamide (XIVc) was
synthesized in a similar way. Yield 51%, mp 72–73°C,
Rf 0.56. Found, %: N 6.34. C22H26N2O6S. Calculated,
%: N 6.28.
11. US Patent no. 2926172, 1960; Ref. Zh., Khim., 1961,
no. 18L278; Austral. Patent no. 220063, 1960; Ref. Zh.,
Khim., 1961, no. 8L347.
N-(exo-5,6-Epoxybicyclo[2.2.1]hept-endo-2-yl-
methyl)-N-(exo-5,6-epoxybicyclo[2.2.1]hept-exo-2-
ylmethyl)-p-nitrobenzenesulfonamide (XIVd) was
synthesized in a similar way. Yield 50%, mp 90–91°C,
Rf 0.52. Found, %: N 6.44. C22H26N2O6S. Calculated,
%: N 6.28.
12. Renise, A., Bondavalli, F., Schenone, P., Adrisani, M.,
Lisa, M., Mattazzo, R., and Matmo, E., Farmaco, Ed.
Sci., 1988, vol. 43, p. 79.
13. UK Patent no. 10894173, 1977; Ref. Zh., Khim., 1977,
no. 21O51.
14. Boehme, W.P., Siegmund, E.A., Scharpf, W.U., and
Schipper, E., J. Med. Pharm. Chem., 1962, vol. 5,
p. 451.
N-(exo-5,6-Epoxybicyclo[2.2.1]hept-endo-2-yl-
methyl)-N-(exo-5,6-epoxybicyclo[2.2.1]hept-exo-2-
ylmethyl)-N'-p-tolylsulfonylurea (XV). p-Toluene-
sulfonyl isocyanate, 0.15 g (0.76 mmol), was added at
room temperature to a solution of 0.17 g (0.74 mmol)
of amine XIIb in 3 ml of benzene. The precipitate was
filtered off, washed with benzene on a filter, dried, and
purified by recrystallization from isopropyl alcohol–
benzene. Yield 71%, mp 186–187°C, Rf 0.74. IR spec-
trum, ν, cm–1: 3370, 3071, 1640, 1550, 1378, 1338,
1270, 1168, 725, 710. Found, %: N 6.82. C24H30N2O3S.
Calculated, %: N 6.57.
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