Synthesis, structure, and transformations of new endic anhydride derivatives

Article abstract of DOI:10.1023/A:1021651712792

4-Azatricyclo[5.2.1.0^2,6]dec-8-ene and its N-phenyl derivative were synthesized by reaction of endic anhydride with amines, transformation of the amido acids thus obtained to imides, and subsequent reduction of the latter with lithium aluminum hydride. The unsubstituted tricyclic amine was brought into reactions with electrophilic reagents: p-toluenesulfonyl chloride, p-toluoyl chloride, m-tolyl isocyanate, phenyl isothiocyanate, and endic anhydride to obtain a number of new derivatives; also, the corresponding salt with 1-adamantanecarboxylic acid was isolated. N-(p-Tolylsulfonyl)- and N-(m-tolylcarbamoyl)-4-azatricyclo[5.2.1.0^2,6]dec-8-enes were oxidized to the corresponding 8,9-epoxy derivatives with monoperoxyphthalic acid. The structure of the products was confirmed by the data of IR, ¹H and ¹³C NMR, and mass spectra. The molecular structures of N-(p-iodophenyl)bicyclo[2.2.1]hept-2-ene-endo-5,endo-6-dicarboximide and N-phenyl-4-azatricyclo[5.2.1.0^2,6]dec-8-ene were established by X-ray analysis.

Full text of DOI:10.1023/A:1021651712792

Russian Journal of Organic Chemistry, Vol. 38, No. 9, 2002, pp. 1299 1308. Translated from Zhurnal Organicheskoi Khimii, Vol. 38, No. 9, 2002,
pp. 1354 1363.
Original Russian Text Copyright
2002 by Tarabara, A. Kas’yan, Krishchik, Shishkina, Shishkin, L. Kas’yan.
Synthesis, Structure, and Transformations
of New Endic Anhydride Derivatives
I. N. Tarabara, A. O. Kas’yan, O. V. Krishchik, S. V. Shishkina,
O. V. Shishkin, and L. I. Kas’yan
Dnepropetrovsk National University, per. Nauchnyi 13, Dnepropetrovsk, 49050 Ukraine
Institute of Single Crystals, pr. Lenina 60, Kharkov, 61001 Ukraine
Received August 8, 2001
Abstract 4-Azatricyclo[5.2.1.02,6]dec-8-ene and its N-phenyl derivative were synthesized by reaction of
endic anhydride with amines, transformation of the amido acids thus obtained to imides, and subsequent
reduction of the latter with lithium aluminum hydride. The unsubstituted tricyclic amine was brought into
reactions with electrophilic reagents: p-toluenesulfonyl chloride, p-toluoyl chloride, m-tolyl isocyanate,
phenyl isothiocyanate, and endic anhydride to obtain a number of new derivatives; also, the corresponding salt
with 1-adamantanecarboxylic acid was isolated. N-(p-Tolylsulfonyl)- and N-(m-tolylcarbamoyl)-4-azatricyclo-
[5.2.1.02,6]dec-8-enes were oxidized to the corresponding 8,9-epoxy derivatives with monoperoxyphthalic
1
acid. The structure of the products was confirmed by the data of IR, H and 13C NMR, and mass spectra. The
molecular structures of N-(p-iodophenyl)bicyclo[2.2.1]hept-2-ene-endo-5,endo-6-dicarboximide and N-phenyl-
4-azatricyclo[5.2.1.02,6]dec-8-ene were established by X-ray analysis.
In the recent years, a number of publications were
concerned with search for new biologically active
compounds among norbornene and norbornane deriva-
tives, specifically among amines containing these
bicyclic fragments. Rigid cage-like structures of such
molecules with a fixed spatial orientation of substit-
uents are convenient models dor studying the relations
between their structure and pharmacological activity
[1]. We previously examined derivatives of exo- and
endo-5-aminomethylbicyclo[2.2.1]hept-2-enes [2] and
exo- and endo-2-aminomethylbicyclo[2.2.1]heptanes
[3] and found that compounds belonging to these
series exhibit neurotropic activity. The goal of the
present work was to synthesize stereochemically pure
derivatives of 4-azatricyclo[5.2.1.02,6]dec-8-ene (IV)
on the basis of accessible endic anhydride (I).
Derivatives of amine IV exhibit various kinds of
pharmacological activity, e.g., hypotensive and tran-
quilizing) [4, 5]. The presence of a hydrogenated iso-
indole fragment makes them structurally related to
lysergic acid whose derivatives are known as hypo-
tensive drugs. Salts of amines related to amine IV
possess ganglioblocking ability and are wholesome
for central nervous system [5, 6]. Starting from amine
IV as a key compound, a large number of derivatives
exhibitng an antiglycemic effect were prepared [6, 7].
Saturated analog of amine IV was used to synthesize
substances active against Gram-positive and Gram-
negative bacteria [8], as well as morphine antagonists
[9]. The above data provide a support to the reason-
ability of developing methods of synthesis of new
4-azatricyclo[5.2.1.02,6]dec-8-ene derivatives.
Scheme 1.
IIa, IIIa, IV, R = H; IIb, IIIb, R = C6H4I-p; V, R = C6H5.
1070-4280/02/3809-1299$27.00 2002 MAIK Nauka/Interperiodica

1300
TARABARA et al.
Fig. 1. Structure of the molecule of N-(p-iodophenyl)bicyclo[2.2.1]hept-2-ene-endo-5,endo-6-dicarboximide (IIIb) according
to the X-ray diffraction data.
1
Imides IIIa and IIIb as precursors of amines
IV and V were synthesized following the most con-
venient way which includes synthesis of amido acids
IIa and IIb as intermediate products. The latter
were obtained under mild conditions by reaction of
equimolar amounts of endic anhydride and appropriate
amine in benzene (Scheme 1); in the synthesis of IIa,
an aqueous solution of ammonia was used. In the IR
spectra of IIa and IIb we observed a set of absorption
bands typical of unsaturated fragments (3050 and
Table 1 gives the H NMR spectral parameters of
compounds I III, which indicate variation of
chemical shifts of protons attached to the tricyclic
skeleton. The lowest chemical shifts of protons on
C1, C4, C5, C6, and C7 are typical of amido acid IIa.
The olefinic protons in IIa are nonequivalent, 6.19
and 5.94 ppm; the corresponding vicinal coupling
3
3
3
constants are as follows: J2, 3 = 5.5, J2, 1 = J3, 4
=
3.0 Hz. Closure of the imide ring is accompanied
by an upfield shift of the bridge 7-H signal (by 0.5
0.6 ppm) and by increase of the geminal coupling
constant Jsyn-7, anti-7 to 8.8 Hz. Table 2 contains the
13C NMR spectral parameters of imides IIIa and IIIb.
The most characteristic are signals from carbon atoms
at the double bond ( 134.32 and 134.83 ppm) and
carbonyl carbon atomsC( C 180.11 and 176.56 ppm for
compounds IIIb and IIIa, respectively).
1
700 cm ) and carboxy and carboxamide groups
1
(3450, 3362, 1700, 1670, 1540, and 1250 cm ) [10].
Crystalline amido avids IIa and IIb were converted
into imides IIIa and IIIb by heating in glacial acetic
acid. The IR spectra of IIIa and IIIb lack carboxy
group absorption, but bands typical of imide carbonyl
1
groups (1775 1750 and 1710 cm ) and unsaturated
norbornene fragments are present. The N H stretch-
Imides IIIa and IIIb were reduced with lithium
aluminum hydride in boiling ether; the reduction of
IIIb was accompanied by hydrodehalogenation, as
ing vibrations of imide IIIa give rise to IR band in
1
the region of 3190 cm [10].
Fig. 2. Structure of the molecule of N-phenyl-4-azatricyclo[5.2.1.02,6]dec-8-ene (V) according to the X-ray diffraction data.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 9 2002

SYNTHESIS, STRUCTURE, AND TRANSFORMATIONS OF NEW ENDIC
1301
Table 1. Parameters of the 1H NMR spectra (chemical shifts , ppm, and coupling constants J, Hz) of compounds
I, IIa, IIIa, and IIIb
Comp. no.
2-H, 3-H
6.32
1-H, 4-H
3.51
5-H, 6-H
3.60,
7-Hsyn, 7-Hanti
Substituent R
I
1.79, 1.58,
2Jsyn-7, anti-7 = 9.0
1.21, 1.12,
3J5, 4
=
3J6, 1 = 3.0
IIa
6.19, 5.94,
3J2, 3 = 5.5,
3J2, 1 = 3J3, 4 = 3.0
6.14
3.14
2.99
7.27, 6.58 (2H, NH2)
2Jsyn-7, anti-7 = 8.3
IIIa
IIIb
3.26
3.41
3.31,
1.67, 1.55,
2Jsyn-7, anti-7 = 8.8
1.78, 1.60,
4.82 (1H, NH)
3J5, 4
3J5, 4
=
=
3J6, 1 = 3.0
3.49,
6.24
7.74 (2H, Harom),
3J6, 1 = 3.0
2Jsyn-7, anti-7 = 8.8 6.90 (2H, Harom
)
Table 2. Parameters of the 13C NMR spectra (chemical shifts C, ppm) of compounds IIa, IIIa, and IIIb
Comp. no.
C2, C3
C1, C4
C5, C6
C7
Substituent R
IIa
IIIa
IIIb
136.16, 134.03
134.32
47.55, 46.20
44.91
49.45, 49.32
47.27
48.92
52.07
52.63
176.00 (CO); 174.56 (CO)
180.11 (CO)
176.56 (CO); 138.42, 128.56
134.83
45.87
46.16
(Carom
)
1
Table 3. Parameters of the H NMR spectra (chemical shifts , ppm, and coupling constants J, Hz) of 4-azatricyclo-
[5.2.1.02,6]dec-8-enes V VI, IX, X, XII, and XIIIa
Comp.
no.
3A-H, 3B-H,
5A-H, 5B-H
8-H, 9-H 1-H, 7-H 2-H, 6-H
10-Hsyn, 10-Hanti
Substituent
IV
6.20
2.82
2.70
2.68, 2.57,
2J3A, 3B = 11.7,
3J3A,2 = 7.5,
3J3B,2 = 1.2
3.23, 2.90,
1.46, 1.42,
2Jsyn-10, anti-10 = 7.8
V
6.16
5.95
3.08
2.80
2.97
2.80
1.61, 1.52,
2Jsyn-10, anti-10 = 8.2
1.46, 1.36
6.45 7.20 (5H, Harom)
2J3A, 3B = 9.6
3.03, 2.69
VI
2.45 (CH3),
7.55 (2H, Harom),
7.32 (2H, Harom
)
IX
X
6.16
6.20
3.31
2.92
2.90
2.57
2.92
2.98
2.57
3.27, 3.06
3.40 3.65
1.53, 1.43
2.27 (CH3),
7.00 7.50 (2H, Harom
7.10 7.26 (5H, Harom),
6.74 (NH)
2.43 (3H, CH3),
7.33 (2H, Harom),
)
1.54, 1.39,
2Jsyn-10, anti-10 = 8.5
1.46, 0.76,
XII
3.46, 2.70,
2J3A, 3B = 10.4
2Jsyn-10, anti-10 = 10.0
7.65 (2H, Harom
)
XIII
3.67,
3.64
3.25
2.59
3.27, 2.78
1.47, 0.86,
2.29 (3H, CH3),
6.82 7.26 (Harom)
2Jsyn-10, anti-10 = 9.9
a
The spectra of compounds IV, V, X, XII, and XIII were measured in chloroform-d (400 MHz), and of VI and IX, in DMSO-d6
(500 MHz).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 9 2002

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TARABARA et al.
Table 4. Parameters of the 13C NMR spectra (chemical shifts C, ppm) of 4-azatricyclo[5.2.1.02,6]dec-8-enes V, X,
XII, and XIII
Comp. no.
C8, C9
C1, C7
C2, C6
C3, C5
C10
Substituent
V
X
136.06
128.91
46.85
46.98
45.85
46.98
50.87
52.07
30.07
52.07
129.25, 115.61, 112.15 (Carom)
177.47 (CS), 139.56, 128.80, 125.79,
125.56 (Carom
21.92 (CH3), 143.89, 131.99, 129.81,
128.12 (Carom
)
XII
49.68
44.06
44.20
40.76
40.69
48.15
29.59
29.84
)
XIII
48.97, 46.95
48.83, 45.81
21.86 (CH3), 153.89 (SO), 138.99,
135.81, 128.87, 124.16, 120.86,
117.18 (Carom
)
1
follows from the data of elemental analysis and H
(Table 3) and 13C NMR spectra (Table 4). The NMR
spectra of amines IV and V contain signals from
protons at C3 and C5 ( 2.5 3.2 ppm) but no signals
from carbonyl carbon atoms. Amine V shows signals
from phenyl protons in the region 6.45 7.20 ppm,
while aromatic protons of imide IIIb appear as two
The coordinates of non-hydrogen atoms in structures
IIIb and V and their equivalent isotropic thermal
parameters are given in Tables 5 and 6.
The bicycloheptene fragment in imides IIIa and
IIIb is a sterically strained system. Presumably, this
is the reason for elongation of skeletal C C bonds,
especially in molecule IIIb. The C3 C7, C5 C6,
and C6 C8 bond lengths in IIIb are 1.64(2), 1.62(2),
and 1.65(2) , respectively; i.e., they are longer than
standard single C C bond (1.53 ). The C C bonds
in the carbon skeleton of V are elongated to a lesser
extent: the corresponding bond lengths are 1.554(8),
1.548(8), and 1.579(9) , respectively. These data
may be explained by change of the substitution pattern
in the nitrogen-containing five-membered ring.
doublets (2H each) at
7.74 and 6.90 ppm.
The steric structure of cyclic amine V was studied
by X-ray analysis. For comparison, the structure of
initial imide IIIb was also examined (Figs. 1, 2).
Table 5. Coordinates ( 104) of nonhydrogen atoms and
2
their equivalent isotropic thermal parameters (
103)
in molecule IIIb
The C7H2 methylene bridge inclines almost equally
with respect to the other parts of the norbornane
Atom
x
y
z
Ueq
fragment: the bond angles C4C3C7 and C2C3C7 are,
respectively, 101.0(1) and 100.0(6) in molecule IIIb
and 101(1) and 99.5(5) in V. In going from IIIb
to V, the degree of puckering of the six-membered
norbornane ring increases: the bond angles C2C3C4 are
108(1) and 105.5(5) , respectively. In addition, struc-
ture V is characterized by greater declination of the
five-membered ring from the bicyclic skeleton: the
C3C2C1 angles in molecules IIIb and V are 112(1)
and 117.3(5) , respectively. Taking into account cis-
junction of the bicycloheptene and tetrahydropyrrole
rings (the torsion angle H2C2C8H8 is 64 ), structure V
is characterized by shortened intramolecular contacts
H1a C4 2.75 and H9a C5 2.67 ; the correspond-
ing sum of the van der Waals radii is 2.87 [11].
The main differences between structures IIIb and
V are observed for the conformation of the nitrogen-
contaning heteroring and mutual arrangement of the
heteroring and benzene ring. The conjugation between
the -systems of the benzene ring at N1 and heteroring
I1
263(1)
2538(4)
2420(4)
2880(4)
2954(6)
3419(5)
4052(6)
3995(6)
3885(5)
3858(6)
4348(6)
3266(5)
2707(6)
2003(6)
1463(7)
942(6)
8063(2)
3487(11)
817(11)
5751(13)
4222(16)
2663(18)
3350(18)
4300(2)
4186(1)
6454(5)
5602(5)
7563(5)
7308(7)
7730(6)
7934(7)
7154(8)
6563(8)
6974(8)
7909(8)
7068(6)
6294(7)
5891(6)
5661(6)
5167(7)
4853(8)
5069(6)
5567(7)
125(1)
29(2)
52(2)
61(3)
41(3)
40(3)
48(4)
64(4)
44(3)
53(4)
65(4)
32(3)
41(3)
34(3)
51(4)
44(3)
46(4)
38(3)
39(3)
N1
O1
O2
C1
C2
C3
C4
C5
2995(17)
984(18)
1330(2)
C6
C7
C8
1064(14)
1655(15)
4496(15)
3706(16)
4739(15)
6539(16)
7344(15)
6337(14)
C9
C10
C11
C12
C13
C14
C15
976(6)
1532(6)
2037(6)
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 9 2002

SYNTHESIS, STRUCTURE, AND TRANSFORMATIONS OF NEW ENDIC
1303
in molecule IIIb is essentially disturbed: the torsion
Table 6. Coordinates ( 104) of nonhydrogen atoms and
their equivalent isotropic thermal parameters (
angle C9N1C10C2 is 61(1) , and the N1 C10 bond is
103)
2
elongated to 1.46(1)
1.371 [12].
relative to the average value
in molecule V
Atom
x
y
z
Ueq
Unlike the planar imide fragment in IIIb, the tetra-
hydropyrrole ring in V adopts an envelope conforma-
tion. The N1 atom deviates by 0.17 from the mean-
square plane including the other pyrrole ring atoms.
N1
C1
1809(7)
2968(9)
1858(9)
3248(10)
3911(9)
2249(10)
383(9)
1427(9)
15(9)
118(8)
4433(7)
5424(9)
5006(8)
3847(8)
2317(9)
1394(8)
2290(8)
3072(10)
3880(8)
3672(8)
4415(9)
3484(8)
3454(8)
4344(8)
5303(10)
5359(9)
1431(5)
2357(5)
3419(5)
4369(5)
3721(5)
3376(5)
3755(6)
4876(6)
2973(6)
1708(6)
327(6)
57(2)
56(2)
56(2)
60(2)
66(2)
54(2)
57(2)
70(2)
55(2)
57(2)
49(2)
55(2)
67(2)
56(2)
60(2)
60(2)
C2
Despite shortened intramolecular contacts H1a C15
C3
2.85 , H2 C9 2.66 , and H15 C1 2.58
C4
(the sum of the van der Waals radii is 2.87
[11]),
C5
the phenyl ring on N1 is coplanar to the five-mem-
bered heteroring plane: the torsion angle C1N1C10C11
is 178.4(6) . However, the N1 C10 is also elongated
[1.413(7) against the standard value 1.371 [12].
C6
C7
C8
C9
Molecules V in crystal are stacked along the 100
crystallographic axis, and molecules IIIb are stacked
along the 010 axis. In the latter case, the stacking is
favored by shortened intermolecular contacts I1 H3a
(x 0.5, y 1.5, z 0.5) 3.04 (the sum of van der
C10
C11
C12
C13
C14
C15
2318(10)
1155(10)
1752(10)
3503(10)
4606(10)
4046(9)
572(6)
1654(7)
1885(5)
988(6)
Waals radii is 3.31 [12]), I1 C3 (x 0.5, y 1.5,
83(6)
z
z
0.5) 3.82 (3.86 ), and I1 H7b (x 0.5, y 0.5,
0.5) 3.24
(3.31 ).
nitrogen atom is located at the endo side of the rigid
bicyclic carbon skeleton. Sulfonamide VI was syn-
thesized in a two-phase system (ether water) using
equimolar amounts of the reactants (amine IV,
p-toluenesulfonyl chloride, and sodium hydroxide).
Amide VII was prepared by an analogous procedure.
Amido acid VIII, urea and thiourea derivatives IX
and X were synthesized in benzene from equimolar
amounts of the reactants, and salt XI was obtained
in acetone.
The IR spectra of compounds VI XI are given
in Table 7. The molecules of all products contain
an unsaturated fragment whose vibrations give rise
to absorption bands in the regions 1575 1550 (C C),
Using unsubstituted amine IV as initial compound,
we obtained a series of its derivatives. Previously,
N-alkyl derivatives of IV were mainly synthesized
and studied [5, 6]. In the present work we obtained
products of reactions of IV with a series of electro-
philic reagents, specifically with p-toluenesulfonyl
chloride, p-toluoyl chloride, endic anhydride, m-tolyl
isocyanate, and phenyl isothiocyanate; also, a salt
of IV with 1-adamantanecarboxylic acid was prepared
(Scheme 2). The yields, melting points, IR spectra,
and elemental analyses of compounds VI XI are
given in Table 7. Most reactions leading to products
VI XI occurred without heating, which suggests
a fairly high reactivity of amine IV in which the
Scheme 2.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 9 2002

1304
TARABARA et al.
Table 7. Yields, melting points, IR frequencies, and elemental analyses of 4-azatricyclo[5.2.1.02,6]dec-8-enes VI XIII
Calculated, %
H
Found, %
Comp. Yield,
IR spectrum,
mp,
C
Formula
1
no.
%
, cm
C
N
C
H
N
VI
81.9
113 114
3050, 1610, 1485, 66.44
1330, 1154, 1120,
1085, 720
6.57
4.84 C16H19NO2S 66.53
6.66
4.93
VII
88.3
Oily
substance
3070, 1640, 1600, 80.63
1440, 1349, 1240,
1060, 723
7.51
5.53 C17H19NO
80.71
7.59
5.62
VIII
IX
87.4
87.5
145 146
133 134
72.24
7.02
7.46
4.68 C18H21NO3
10.45 C17H20N2O
72.37
76.16
7.17
7.49
4.80
3300, 3030, 1635, 76.12
1610, 1548, 1484,
1230, 718
10.47
X
75.0
195 196
3254, 3048, 1535, 71.10
1452, 1337, 1294,
1240, 698
6.67
10.37 C16H18N2S
4.44 C20H29NO2
71.02
76.23
6.57
10.31
XI
65.0
90.9
214 215
168 169
3055, 2440, 1600, 76.19
1574, 1415, 720
9.21
6.23
9.29
6.19
4.48
4.64
XII
3045, 1596, 1481, 62.95
1329, 1160, 1111,
1088, 854
4.59 C16H19NO3S 62.19
9.86 C17H20N2O2 71.90
XIII
95.2
150 152
3291, 3032, 1640, 71.83
1608, 1549, 1489,
1300, 1233, 973,
907, 850
7.04
7.12
9.95
1
2
2
3065 3040 (Csp H), and 720 700 cm ( Csp H).
The unusual frequency of the C C band is explained
by steric strain, and its low intensity, by high sym-
metry of the unsaturated fragment [13]. Moreover, this
band is obscured by absorption of both N H ( N H)
and aromatic moieties. Sulfonamide VI shows in the
IR spectrum absorption bands from the sulfonyl group
which belong, respectively, to its asymmetric and
symmetric stretching vibrations.
Table 3 contains H NMR spectral parameters of
compounds VI, IX, and X. These, as well as amines
IV and V, are characterized by equivalent signals
1
of protons at C8/C9, C1/C7, and C3/C5 and by a weak
difference in the chemical shifts of 2-H and 6-H.
A considerable nonequivalence (up to 0.4 ppm) was
observed for the 3-HA and 3-HB protons and also
for protons on C5; a similar pattern was observed
1
(1330 and 1120 cm ), and compounds VII IX are
characterized by the presence of amide bands arising
from stretching vibrations of the carbonyl group
(1635 1610 cm ), bending vibrations of the N H
bonds (1548 1535 cm ), and stretching vibrations of
the C N bonds (1240 1230 cm ). The spectrum
of X lacks amide I band, but an absorption band at
1337 cm is present, which belongs to stretching
vibrations of the thiocarbonyl group [10]. In the IR
1
1
previously in the H NMR spectrum of amine V. The
1
spectra of VI, IX, and X also contain signals from
substituents on the nitrogen atom, namely aromatic
fragments and methyl groups ( 2.45 and 2.27 ppm)
in compounds VI and IX.
1
1
The 13C NMR parameters of compound X (Table 4)
spectrum of salt XI we clearly observed a broad
1
indicate the presence in its molecule of a double bond
ammonium band in the region 3000 2300 cm
(
128.91 ppm), benzene ring, and thiocarbonyl
C
(
asNH+2 and sNH2+), which overlaps with the C H
group (
177.47 ppm); the signals from C1, C7,
bands. Bending vibrations of the NH+2 group appear
C
1
at about 1600 cm . The carboxylate moiety gives rise
to absorption bands at 1580 1560 and 1415 cm ,
C2, and C6 characteristically coincide with each other
( 46.98 ppm). The signals from the skeletal carbon
C
1
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 9 2002

SYNTHESIS, STRUCTURE, AND TRANSFORMATIONS OF NEW ENDIC
1305
Scheme 3.
atoms are very similar to those observed in the spec-
trum of amine V.
one proton of the methylene bridge, which is located
directly above the oxirane ring plane (10-Hanti), shows
an upfield shift due to magnetically anisotropic effect
of the epoxy fragment. The data in Table 3 indicate
that such effect is also typical of compounds XII and
XIII: the corresponding upfield shift relative to
unsaturated analogs VI and IX is 0.60 and 0.57 ppm,
in keeping with the assumed structures. An additional
proof is given by the 13C NMR spectra (Table 4),
Analysis of the mass spectrum of compound X
showed that fragmentation of its molecular ion fol-
lows two main pathways (Scheme 3). The first of
these (A) involves retro-Diels Alder decomposition
with formation of ions F1 and F2; elimination of
phenyl isothiocyanate from the latter gives ion F3.
According to pathway B, ion F4 is formed in the first
stage via elimination of PhNH species. Ion F4 thus
formed is converted into F5 which is likely to exist
as more stable isothiocyanate. In keeping with the
spectral data, pathway A prevails: the abundance of
F2 (m/z 205) approaches 100%.
Compounds VI and IX were brought into reaction
with monoperoxyphthalic acid generated in situ from
phthalic anhydride and 40% hydrogen peroxide. As
a result, epoxy derivatives XII and XIII were ob-
tained (Scheme 4, Table 7).
where the upfield shift of the C10 signal (
29
30 ppm) attains 20 ppm, as compared withCcom-
pounds V and X [15].
Taking into account the above data indicating
stereoselective exo attack by peroxy acid on the
double bond of new tricyclic compounds VI and IX,
unusual position of the 8-H and 9-H signals should be
noted ( 3.31 3.70 ppm). Such signals are more
typical of endo-epoxy derivatives of the same series
[16], whereas analogous signals of the exo isomers
were usually observed at
3.00 3.20 ppm [14].
Presumably, this pattern is explained by magnetically
anisotropic effect of the endo-oriented hydrogenated
pyrrole fragment or benzene ring in the arylsulfonyl
or aroyl group.
Scheme 4.
EXPERIMENTAL
The IR spectra were recorded on a Specord 75IR
spectrometer from samples pelleted with potassium
bromide. The 1H NMR spectra were obtained on
Varian VXR-300 (300 MHz) and Gemini-BB instru-
ments (400 and 500 MHz) from solutions in CDCl3
or DMSO-d6 using hexamethyldisiloxane as internal
reference. The 13C NMR spectra were measured on
a Gemini-BB spectrometer operating at 50.3 and
100.7 MHz. The progress of reactions was monitored,
and the purity of products was checked, by TLC on
XII, X = SO2C6H4CH3-p; XIII, X = CONHC6H4CH3-m.
The IR spectra of compounds XII and XIII contain
1
a characteristic band at 854 and 850 cm , respec-
tively, which belongs to vibrations of the oxirane
1
C O bond [14]. In the H NMR spectra of epoxynor-
bornanes with exo orientation of the epoxy group,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 9 2002

1306
TARABARA et al.
Silufol UV-254 plates using diethyl ether as eluent;
the chromatograms were developed with iodine vapor.
The elemental analyses were obtained on a Karlo Erba
analyzer.
we added dropwise with stirring 8.2 g (0.12 mol) of
25% aqueous ammonia, and the mixture was stirred
until the reaction was complete (TLC). The resulting
amido acid was filtered off, washed with benzene,
and subjected to further purification. Yield 81.7%,
X-Ray diffraction data for compound IIIb.
Monoclinic crystals. C15H12INO2. Unit cell param-
eters (20 C): a = 26.241 (5), b = 7.042 (1), c =
1
mp 137 138 C. IR spectrum, , cm : 3450, 3362,
3080, 3050, 1700, 1670, 1540, 1395, 1338, 1252,
1200, 790, 700. Found, %: C 59.73; H 6.16; N 7.86.
C9H11NO3. Calculated, %: C 59.67; H 6.08; N 7.73.
18.328(4)
;
= 119.4(1) ; V = 2949(1) 3; Mr =
365.16; Z = 8; space group C2/c; dcalc = 1.645 g/cm3;
1
(MoK ) = 2.168 mm , F(000) = 1424. The unit
endo-5-(p-Iodophenylcarbamoyl)bicyclo[2.2.1]-
hept-2-ene-endo-6-carboxylic acid (IIb) was syn-
thesized in a similar way from 0.82 g (0.005 mol) of
endic anhydride and 1.09 g (0.005 mol) of p-iodo-
aniline. Yield 71.9%, mp 145 146 C. IR spectrum, ,
cell parameters and intensities of 2113 reflections
(2062 independent reflections with Rint = 0.098) were
measured on a Siemens P3/PC automatic four-circle
diffractometer (MoK , graphite monochromator, 2 /
1
scanning to 2
= 50 ). The structure was solved by
cm : 3350, 3078, 1710, 1665, 1548, 1246, 708.
max
the direct method using SHELX97 software package
[17]. The absorption was taken into account by semi-
empirical procedure from the results of -scanning,
Tmin = 0.037, Tmax = 0.44. The positions of hydrogen
atoms were determined from the difference synthesis
of electron density and were refined according to
the rider model with Uiso = 1.2Ueq of nonhydrogen
atom attached to the given hydrogen atom. The struc-
ture was refined with respect to F2 by the full-matrix
least-squares procedure in anisotropic approximation
for nonhydrogen atoms [to wR2 = 0.293 from 2062 re-
flections; R1 = 0.089 from 800 reflections with F >
4 (F), S = 0.899].
Bicyclo[2.2.1]hept-2-ene-endo-5,endo-6-dicarbox-
imide (IIIa). A mixture of 11.0 g (0.061 mol) of
amido acid IIa and 50 ml of glacial acetic acid was
refluxed for 6 h. When the reaction was complete
(TLC), the solvent was distilled off, the residue was
treated with water, and the precipitate was filtered
off and purified. Yield 78.4%, mp 174 175 C. IR
1
spectrum, , cm : 3190, 3151, 3064, 1751, 1728,
1695, 1353, 1274, 1184, 728. Found, %: C 66.43;
H 5.71; N 8.76. C9H9NO2. Calculated, %: C 66.26;
H 5.52; N 8.59.
N-(p-Iodophenyl)bicyclo[2.2.1]hept-2-ene-endo-
5,endo-6-dicarboximide (IIIb) was synthesized in
a similar way from 1.2 g (0.003 mol) of amido acid
X-Ray diffraction data for compound V. Mono-
clinic crystals. C15H17N. Unit cell parameters (20 C):
IIb. Yield 70.1%, mp 178 180 C. IR spectrum,
,
a = 6.530(2), b = 8.046(3), c = 11.943(5)
;
=
1
cm : 3082, 2981, 1774, 1709, 1456, 1391, 1125,
1056, 838. Found, %: C 49.22; H 3.24; N 3.93.
C15H12INO2. Calculated, %: C 49.32; H 3.29; N 3.84.
99.77(3) ; V = 618.4(4) 3; Mr = 160.19; Z = 2;
space group P2(1); dcalc = 0.860 g/cm3; (MoK ) =
1
0.056 mm ; F(000) = 170. The unit cell parameters
4-Azatricyclo[5.2.1.02,6]dec-8-ene (IV). Imide
IIIa, 7.5 g (0.046 mol), was added in small portions
under stirring to a suspension of 7.0 g (0.184 mol) of
lithium aluminum hydride in 100 ml of dry diethyl
ether. The mixture was stirred at 35 C until the reac-
tion was complete (TLC). Excess reducing agent was
decomposed with cold water, the precipitate was
filtered off, the organic phase was dried over calcined
magnesium sulfate, the solvent was removed, and the
product was subjected to purification. Yield 80.5%
mp 55 56 C; published data [18]: mp 59 60 C. IR
and intensities of 1112 reflections (1023 independent
reflections with Rint = 0.088) were measured on
a Siemens P3/PC automatic four-circle diffractometer
(MoK , graphite monochromator, 2 / scanning to
2
= 50 ). The structure was solved by the direct
memthaxod using SHELX97 software package. The posi-
tions of hydrogen atoms were determined from the
difference synthesis and were refined using the rider
model with Uiso = 1.2Ueq of nonhydrogen atom
attached to the given hydrogen atom. The structure
was refined with respect to F2 by the full-matrix least-
squares procedure in anisotropic approximation for
nonhydrogen atoms [to wR2 = 0.124 from 1023 reflec-
tions; R1 = 0.051 from 483 reflections with F >
4 (F), S = 0.86].
endo-5-Carbamoylbicyclo[2.2.1]hept-2-ene-endo-
6-carboxylic acid (IIa). To a solution of 13.1 g
(0.08 mol) of endic anhydride (I) in 70 ml of benzene
1
spectrum, , cm : 3350, 3050, 2720, 1625, 1512,
1255, 1230, 820, 720.
N-Phenyl-4-azatricyclo[5.2.1.02,6]dec-8-ene (V)
was synthesized in a similar way. Yield 68.3%,
1
mp 82 84 C. IR spectrum, , cm : 1600, 1510, 1480,
1373, 1200, 746. Found, %: C 85.25; H 7.94; N 6.71.
C15H17N. Calculated, %: C 85.31; H 7.94; N 6.64.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 9 2002

SYNTHESIS, STRUCTURE, AND TRANSFORMATIONS OF NEW ENDIC
1307
N-(p-Tolylsulfonyl)-4-azatricyclo[5.2.1.02,6]dec-8-
ene (VI). A solution of 0.28 g (0.0015 mol) of p-tolu-
enesulfonyl chloride in 5 ml of ether was added
dropwise under stirring to a mixture of 0.20 g
(0.0015 mol) of amine IV in 10 ml of ether and
0.25 ml (0.0015 mol) of 20% aqueous NaOH. The
mixture was stirred until the reaction was complete
(TLC). The ether was removed, the solid residue was
dissolved in 20 ml of a 1:1 chloroform water mix-
ture, the organic layer was separated and evaporated,
and the product was recrystallized from isopropyl
alcohol.
and the residue was recrystallized from isopropyl
alcohol.
exo-8,9-Epoxy-N-(m-tolylcarbamoyl)-4-azatri-
cyclo[5.2.1.02,6]decane (XIII) was synthesized in
a similar way. The properties of compounds XII and
XIII are given in Tables 3, 4, and 7.
REFERENCES
1. Krieger, H., Arzneim.-Forsch., 1968, vol. 18, pp. 129
134, 324 330, 487 493.
N-(p-Toluoyl)-4-azatricyclo[5.2.1.02,6]-dec-8-ene
(VII) was synthesized in a similar way from 0.20 g
of amine IV and 0.26 g of p-toluoyl chloride. The
physical properties and spectral parameters of com-
pounds VI and VII are given in Tables 3, 4, and 7.
N-(endo-6-Carboxybicyclo[2.2.1]hept-2-ene-
endo-5-carbonyl)-4-azatricyclo[5.2.1.02,6]dec-8-ene
(VIII). Endic anhydride, 0.12 g (0.00074 mol), was
added to a solution of 0.1 g (0.00074 mol) of amine
IV in 10 ml of benzene, and the mixture was left to
stand until the reaction was complete (TLC). The
precipitate was filtered off, washed with benzene,
dried, and recrystallized from benzene (Table 7).
N-(m-Tolylcarbamoyl)-4-azatricyclo[5.2.1.02,6]-
dec-8-ene (IX) and N-[phenyl(thiocarbamoyl)]-4-
azatricyclo[5.2.1.02,6]dec-8-ene (X) were synthesized
by a similar procedure from 0.2 g (0.0015 mol) of
amine IV and an equimolar amount of m-tolyl iso-
cyanate or phenyl isothiocyanate, respectively. The
yields, melting points, and analytical and spectral
data of compounds IX and X are given in Tables 3,
4, and 7.
4-Azoniatricyclo[5.2.1.02,6]dec-8-ene 1-adaman-
tanecarboxylate (XI). To a solution of 0.10 g
(0.00074 mol) of amine IV in 5 ml of acetone we
added a solution of 0.13 g (0.00074 mol) of 1-ada-
mantanecarboxylic acid in 5 ml of acetone. Crystals
separated and were filtered off, dried, and recrystal-
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[5.2.1.02,6]decane (XII). To a mixture of 0.2 g
(0.65 mmol) of sulfonamide VI, 0.19 g (1.29 mmol)
of phthalic anhydride, and 0.02 g (0.32 mmol) of urea
in 15 ml of ethyl acetate we added under stirring
0.125 g (1.29 mmol) of 35% hydrogen peroxide, and
the mixture was stirred until the reaction was com-
plete (TLC). The mixture was neutralized with
a saturated solution of sodium hydrogen carbonate,
the organic layer was separated and dried over cal-
cined magnesium sulfate, the solvent was removed,
8. Albrecht, R., Gutsche, K., Kessler, H.-J., and
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