Synthesis and epoxidation of 5-(2-aminoethyl)bicyclo[2.2.1]hept-2-ene derivatives

Article abstract of DOI:10.1023/A:1015338305344

A number of derivatives of 5-(2-aminoethyl)bicyclo[2.2.1]hept-2-ene (85-90% of the endo isomer) were synthesized by reactions with p-nitrobenzenesulfonyl chloride, p-toluenesulfonyl chloride, benzoyl chloride, p-nitrobenzoyl chloride, benzyl isocyanate, m-tolyl isocyanate, phenyl isothiocyanate, and endic anhydride. By reactions of the resulting sulfon- and carboxamides with peroxyphthalic acid generated in situ from phthalic anhydride and 40-45% hydrogen peroxide the corresponding epoxy derivatives were obtained. These reactions were not accompanied by heterocyclization into azabrendane derivatives, which is typical of homologous N-(p-nitrophenylsulfonyl)-endo-5-aminomethylbicyclo[2.2.1]hept-2-ene.

Full text of DOI:10.1023/A:1015338305344

Russian Journal of Organic Chemistry, Vol. 38, No. 1, 2002, pp. 19 25. Translated from Zhurnal Organicheskoi Khimii, Vol. 38, No. 1, 2002,
pp. 29 35.
Original Russian Text Copyright
2002 by L. Kas’yan, Tarabara, A. Kas’yan.
Synthesis and Epoxidation
of 5-(2-Aminoethyl)bicyclo[2.2.1]hept-2-ene Derivatives
L. I. Kas’yan, I. N. Tarabara, and A. O. Kas’yan
Dnepropetrovsk State University, per. Nauchnyi 13, Dnepropetrovsk, 49050 Ukraine
Ukrainian State University of Chemical Technology
Received August 9, 2000
Abstract A number of derivatives of 5-(2-aminoethyl)bicyclo[2.2.1]hept-2-ene (85 90% of the endo isomer)
were synthesized by reactions with p-nitrobenzenesulfonyl chloride, p-toluenesulfonyl chloride, benzoyl
chloride, p-nitrobenzoyl chloride, benzyl isocyanate, m-tolyl isocyanate, phenyl isothiocyanate, and endic
anhydride. By reactions of the resulting sulfon- and carboxamides with peroxyphthalic acid generated in situ
from phthalic anhydride and 40 45% hydrogen peroxide the corresponding epoxy derivatives were obtained.
These reactions were not accompanied by heterocyclization into azabrendane derivatives, which is typical
of homologous N-(p-nitrophenylsulfonyl)-endo-5-aminomethylbicyclo[2.2.1]hept-2-ene.
Pharmacophoric norbornene fragment, as well as
of the substituent in the norbornene fragment affects
related norbornane and adamantane moeities, acquires both spectral parameters and chemical behavior of
a specific importance in molecules of amines, many
of which are used as medicines [1]. Among amines
containing a norbornene fragment, the most widely
known and extensively studied are stereoisomeric exo-
and endo-5-aminomethylbicyclo[2.2.1]hept-2-enes Ia
and Ib (Scheme 1).
amine derivatives in reactions with peroxy acids.
Stereochemical features of sulfonamides derived from
amines Ia and Ib determine both the kind and the
strength of neurotropic (analgetic, anticonvulsant,
antihypoxic, tranquilizing) and antiphlogistic activity.
Homologs of amines Ia and Ib were studied very
poorly. A saturated analog of II was used as starting
Scheme 1.
compound for preparation of adenosine A receptor
2
agonists [9]. We expected that variation of the length
of the hydrocarbon chain connecting the amino group
and the bicyclic skeleton should give rise to new
biologically active substances. This assumption was
based, in particular, on the new data on biological
activity of adamantane amino derivatives: separation
of the amino group from the adamantane core by
2
3 methylene units leads to increase of antiviral
activity [10].
In the present work we synthesized derivatives of
amine II and studied their reactions with peroxy-
phthalic acid. Amine II was synthesized from the
Diels Alder adduct of cyclopentadiene and acrolein,
which was obtained under mild conditions of kinetic
control. The major product was the corresponding
endo isomer (III) [11] (Scheme 2). Amine II
was synthesized from aldehyde III by modified proce-
dure [12] via condensation with nitromethane in
alkaline medium, followed by reduction of unsaturated
nitro compound IV with lithium aluminum hydride.
In the recent years various derivatives of amines
Ia and Ib were synthesized, such as sulfonamides [2],
carboxamides [3], urea and thiourea derivatives [4],
and products of reactions with endic, naphthalic, and
substituted naphthalic anhydrides [5, 6]. The spectral
parameters [7] and biological activity of these com-
pounds were studied [8]. It was found that orientation
1
070-4280/02/3801-0019$27.00 2002 MAIK Nauka/Interperiodica

2
0
KAS’YAN et al.
The reduction occurred chemoselectively, involving
two of the three possible centers, and target product
II was obtained in 65 70% yield.
carbon carbon bonds in the two bicyclic fragments.
The corresponding band in the IR spectra of the other
compounds is obscured by absorption of the amino
group ( NH) and aromatic fragments [14]. Imide IX
is also characterized by the presence in the IR spec-
Scheme 2.
1
trum of two carbonyl bands at 1750 and 1700 cm
and a band at 3070 3060 cm 1 which belongs to
stretching vibrations of olefinic C H bonds in the
norbornene fragments. Analogous bands in the spectra
of the other derivatives are overlapped by absorption
of aromatic C H bonds. Bending vibrations of the
1
H C bonds in IX appear at 730 cm .
1
Table 2 contains the H NMR spectra of com-
1
pounds Ib, II, Va, VIa, VIIa; for comparison, the H
NMR spectrum of previously described biologically
active sulfonamide X [15] is also given. Apart from
1
some similarity, the H NMR spectra of derivatives
Amine II was brought into reactions with a number
of electrophilic reagents: p-nitrobenzenesulfonyl
chloride, p-toluenesulfonyl chloride, p-nitrobenzoyl
chloride, benzoyl chloride, benzyl isocyanate, m-tolyl
isocyanate, phenyl isothiocyanate, and endic anhy-
dride (Scheme 3). Sulfonamides Va and Vb were
obtained in the two-phase system diethyl ether 20%
aqueous sodium hydroxide; carboxamides VIa and
VIb were synthesized in chloroform in the presence
of pyridine, and the other reactions were carried out
in benzene. The reaction with endic anhydride under
such mild conditions usually leads to formation of
amido acids [5]; however, from amine II we obtained
imide IX. The yields, melting points, IR spectra,
and elemental analyses of products V IX are given
in Table 1.
of amines II and Ib have considerable differences.
The predominant endo orientation of the 5-substituent
Scheme 3.
The IR spectra of amides VIa and VIb and ureas
VIIa and VIIb characteristically contain amide
absorption bands in the regions 1640 1630 ( C O),
1
1
570 1550 ( N H), and 1270 1250 cm ( C N).
The IR spectrum of thiourea VIII lacks amide I band
1
but displays absorption at 1330 cm which was
assigned to stretching vibrations of the C S group.
Sulfonamides Va and Vb clearly show in the IR
spectra absorption bands due to SO group at 1360
2
1
1
340 and 1175 1155 cm [13]. The nitro group in
molecules Va and VIa gives rise to absorption bands
1
at 1545 1520 and 1350 1330 cm , typical of its
symmetric and antisymmetric vibrations. All amine II
derivatives show in the IR spectra absorption at 3400
3
200 cm 1 due to stretching vibrations of the N H
bond; the spectra of VIIa, VIIb, and VIII are charac-
terized by the presence of two bands in that region,
whereas no N H band is observed in the spectrum
of imide IX. The latter gives a weak absorption at
V, R = C H NO -p (a), C H CH -p (b); VI, R = C H NO -p
6
4
2
6
4
3
6
4
2
1
581 cm 1 due to stretching vibrations of double
(a), C H (b); VII, R = CH C H (a), C H CH -m (b).
6 5 2 6 5 6 4 3
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 1 2002

SYNTHESIS AND EPOXIDATION OF 5-(2-AMINOETHYL)BICYCLO[2.2.1]. . .
21
amines Ia and Ib and their numerous derivatives [7].
As follows from the signal intensities, the fraction of
the major endo isomer of II is 86%. Comparison of
1
of the H NMR spectra of amines Ib and II shows
some influence of the length of the side chain on the
spectral parameters. The signals of Ib were assigned
on the basis of the two-dimensional COSY spectrum.
The spectra of Va, VIa, and VIIa are characterized
8
by upfield shift of the C H signals to 1.3 1.5 ppm
2
9
and appearance of signals from C H in the region
2
9
3
.0 3.5 ppm. In the above series, the C H protons
2
of amide VIa are the most deshielded, as well as the
other protons in its molecule. Molecules of amine II
and its derivatives each have four methylene groups:
in II was derived from the different chemical shifts
of 2-H and 3-H ( 6.12 and 5.96 ppm, respectively),
similar chemical shifts of protons in the bridgehead
positions (1-H and 4-H; 2.77 and 2.76 ppm), and
the position of the endo-6-H signal ( 0.53 ppm) due
to magnetically anisotropic effect of the exocyclic
6
7
8
9
C H , C H , C H , and C H . The corresponding
2
2
2
2
proton coupling constants considerably differ from
each other; e.g., for amide VIa they are 11.4, 8.4,
13.4, and 14.4 Hz, respectively.
Table 3 contains the 13C NMR spectral parameters
of compounds Va, VIa, and VIIa. For comparison,
the data for N-(3,4-dichlorophenylsulfonyl)-endo-5-
aminomethylbicyclo[2.2.1]hept-2-ene (XI) are also
given (its NOESY spectrum was also measured). In
the 13C NMR spectra of amine II derivatives, recorded
5
8
C
C bond [2, 4, 7]. The exo isomer of II gives the
following signals, , ppm: 6.08 (2-H), 6.04 (3-H),
1
2.81 (1-H), 2.51 (4-H). The H NMR parameters of
compound II are consistent with the criteria developed
by us previously while studying stereoisomeric
Table 1. Yields, melting points, IR spectra, and elemental analyses of compounds Va, Vb, VIa, VIb, VIIa, VIIb, VIII,
IX, XIVa, and XIVb
Found, %
H
Calculated, %
Comp. Yield,
mp,a
C
IR spectrum, , cm 1
Formula
no.
%
C
N
C
H
N
Va
89
85
91
85 87 3265, 3058, 1533, 1350, 55.93 5.39
331, 1308, 1160, 720
77 78 3290, 1538, 1345, 1330,
154
123 124 3293, 3057, 1640, 1556, 67.07 6.27
522, 1347, 1279, 716
8.74 C H N O S 55.90 5.59
8.70
4.81
9.79
5.81
1
5 18 2 4
1
Vb
4.75 C H NO S
65.98 7.22
67.13 6.29
79.67 7.88
1
6
21
2
1
VIa
9.70 C H N O
16 18 2 3
1
VIb
VIIa
71
84
113 114
86 88 3333, 3030, 1630, 1572, 77.43 8.07 10.30 C H N O
5.91 C H NO
1
6
19
75.55 8.15 10.37
75.55 8.15 10.37
70.59 7.35 10.29
1
7
22
2
1
453, 1306, 1253, 720
VIIb
VIII
IX
87
67
83
77
89
85 86 3342, 3035, 1638, 1560, 75.61 8.13 10.31 C H N O
1
7 22 2
1
440, 1310, 1255, 718
89 90 3360, 3200, 3070, 1550, 70.48 7.31 10.21 C H N S
1
6 20 2
1
326, 1250, 1180, 718
134 136 3070, 1750, 1700, 1581,
344, 1240, 1180, 730
98 100 3310, 1540, 1356, 1318,
170, 1100, 856
88 90 3350, 1660, 1556, 1535, 63.53 5.90
350, 1310, 1118, 860
4.83 C H NO
2
76.32 7.42
4.95
8.28
9.27
1
8
21
1
XIVa
XIVb
8.34 C H N O S 53.25 5.32
1
5
18
2
5
1
9.32 C H N O
63.58 5.96
1
6 18 2
4
1
a
From aqueous ethanol.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 1 2002

2
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KAS’YAN et al.
Table 2. 1H NMR spectra of Ib, II, Va, VIa, VIIa, and X ( , ppm, J, Hz)
Comp.
no.
syn-7-H,
anti-7-H
NH,
Harom
1-H 2-H, 3-H 4-H 5-H
exo-6-H
endo-H
8-H , 8-H
9-H , 9-H
A B
A
B
Ib
2.81 6.07, 5.86, 2.72 2.03
1.76,
0.42,
1.37, 1.18,
2.37, 2.29,
J8,8 = 12.2,
J8A,5 = 7.3,
J8B,5 = 8.2
1.21
(NH)
3
2
3
3
J6,6 = 11.4, 3J6,5 = 4.1, 2J7,7 = 7.9
2
3
3
J2,3 = 5.8,
J2,1 = 2.8,
3
4
J6,5 = 9.2,
J6,1 = 3.9
J6,7s = 2.6
3
J3,4 = 3.0
II
2.77 6.12, 5.92, 2.76 2.04
1.85,
0.53,
1.38, 1.22,
1.32, 1.26,
J8,8 = 12.6,
J8A,5 = 5.4,
J8B,5 = 6.0
2.79, 2.66,
J9,9 = 14.7,
J9A,8 = 7.2,
J9B,8 = 7.2
1.56
(NH)
3
2
3
3
3
2
2
3
3
2
3
3
J2,3 = 5.4,
J2,1 = 2.7,
J6,6 = 11.4, J6,5 = 4.0, J7,7 = 8.4
J6,5 = 9.3,
J6,1 = 3.8
3
4
J6,7s = 2.3
3
J3,4 = 3.0
Va
2.81 6.17, 5.89, 2.74 2.03
1.86,
0.50,
1.44, 1.23,
J7,7 = 8.3 J8,8 = 12.4,
1.37, 1.30,
3.27, 3.09,
J9,9 = 13.4,
J9A,8 = 7.4,
J9B,8 = 7.4
5.03
(NH)
8.43,
8.13
3
2
3
J6,6 = 11.4, 3J6,5 = 4.0,
2
2
2
3
3
J2,3 = 5.7,
J2,1 = 3.0,
3
4
3
J6,1 = 3.9
J6,7s = 2.7
J8A,5 = 5.5,
J8B,5 = 5.6
3
3
J3,4 = 3.0
VIa 2.84 6.17, 5.96, 2.83 2.08
1.92,
0.59,
1.51, 1.26,
J7,7 = 8.4 J8,8 = 13.4,
1.46, 1.40,
3.54, 3.46,
J9,9 = 14.4,
J9A,8 = 7.1,
J9B,8 = 6.6
6.46
(NH)
8.27,
7.96
3
2
3
3
3
2
2
2
3
3
J2,3 = 5.7,
J2,1 = 3.0,
J6,6 = 11.4, J6,5 = 4.3,
J6,5 = 9.1,
J6,1 = 3.8
3
4
3
J6,7s = 2.7
J8A,5 = 7.4,
J8B,5 = 7.4
3
3
J3,4 = 2.7
VIIa 2.82 6.17, 5.97, 2.79 2.01
1.88,
0.55,
1.45, 1.26,
1.37, 1.32
3.17, 3.14,
J9,9 = 13.6,
J9A,8 = 7.4,
J9B,8 = 7.0
5.38,
5.01
(NH)
7.32
3
2
3
3
3
2
3
3
3
J2,3 = 5.7,
J2,1 = 3.0,
J6,6 = 11.3, J6,5 = 4.0, J7,7 = 7.8
J6,5 = 9.0,
J6,1 = 3.7
3
4
J6,7s = 2.7
3
J3,4 = 2.7
X
2.75 6.08, 5.73, 2.73 2.12
1.74,
0.40,
1.38, 1.15,
2.67, 2.58,
4.79
(NH)
8.31,
7.98
3
2
3
3
3
2
J7,7 = 8.4 2J
J2,3 = 5.8,
J2,1 = 3.0,
J6,6 = 11.8, J6,5 = 4.0,
J6,5 = 8.9,
J6,1 = 3.8
= 12.6
8,8
3
4
J6,7s = 2.6
3
J3,4 = 2.8
7
8
by the Rubenstein Nakashima technique, the C , C ,
5-aminomethylbicyclo[2.2.1]hept-2-enes with peroxy-
phthalic acid take different pathways, depending on
the substituent on the nitrogen. In particular, carbox-
amide derivatives are converted into epoxy com-
pounds XII [17], whereas sulfonamides give rise to
substituted 4-azatricyclo[4.2.1.0 ]nonanes (aza-
brendanes) XIII [18] (Scheme 4).
9
and C signals are located at
49.6 49.7, 39.8 42.5,
and 34.6 35.2 ppm, respectively. All compounds have
nonequivalent carbon atoms at the double bond,
C
1
37.3 137.8 and 131.8 132.3 ppm.
C
3
.7
1
Urea VIIa shows in the H NMR spectrum signals
from the benzyl group at 4.55 and 7.32 ppm and two
nonequivalent NH protons at 5.38 and 5.01 ppm.
Analogous NH protons in compounds Va and VIa
give rise to signals at 5.03 and 6.46 ppm. The car-
bonyl carbon signals of VIa and VIIa appear in the
Scheme 4.
1
3
C NMR spectra at
165.5 and 158.7 ppm, respec-
C
tively, and methylene carbon nucleus of the benzyl
group gives a signal at 44.4 ppm.
C
We also continued our studies on heterocyclization
by the action of peroxy acids [16] of compounds in
which arenesulfonamide and arenecarboxamide frag-
ments are separated from the norbornene framework
by different numbers of methylene units. According
to our previous data, reactions of substituted endo-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 1 2002

SYNTHESIS AND EPOXIDATION OF 5-(2-AMINOETHYL)BICYCLO[2.2.1]. . .
Table 3. 13C NMR spectra of 5-(2-aminoethyl)bicyclo[2.2.1]hept-2-ene derivatives, C, ppm
Comp.
23
C1
C2
C3
C4
C5
C6
C7
C8
C9
C O, Carom
no.
Va
42.71 137.78 131.84
42.61 137.64 132.07
45.31
45.58
45.50
43.9
35.84
36.46
36.23
38.9
32.08
32.36
32.28
30.0
49.66
49.72
49.66
49.5
34.75
34.62
35.24
47.2
42.53 146.08, 136.59, 128.42,
24.56
39.84 165.52, 130.76, 128.18,
23.86, 123.59
39.79 158.70, 139.58, 128.64,
27.41 127.22, 44.42
139.8, 137.4, 133.7,
31.1, 126.1
1
VIa
1
VIIa 42.56 137.32 132.27
XI 42.3 138.2 131.5
1
1
The possibility for heterocyclization with formation
of six- and seven-membered analogs of azabrendanes
XIII was studied using compounds Va and VIa as
examples. The reactions were carried out in chloro-
form with peroxyphthalic acid generated in situ from
phthalic anhydride and 40 45% aqueous hydrogen
peroxide [18]. As a result, we isolated epoxy deriva-
tives XIVa and XIVb as the only reaction products
Our results show that, unlike sulfonamides derived
from aminomethylnorbornene Ib, no heterocyclization
of their analogs having two methylene units between
the amino group and bicyclic fragment occurs in reac-
tions with peroxy acids.
EXPERIMENTAL
The IR spectra were recorded on a Specord 75IR
spectrometer from samples prepared as thin films
(
Table 1). Their structure was confirmed by the IR
and H NMR spectra.
1
1
13
or KBr pellets. The H and C NMR spectra were
obtained on a Varian VXR-300 instrument at 300 and
75.4 MHz, respectively, using chloroform-d as solvent
and HMDS as internal reference. The progress of
reactions and the purity of products were monitored
by TLC on Silufol UV-254 plates using diethyl ether
as eluent and iodine vapor as developer.
Bicyclo[2.2.1]hept-2-ene-5-carbaldehyde (III).
Freshly distilled cyclopentadiene [19], 17.2 g
(21.5 ml, 0.26 mol) was slowly added with stirring
to 14.6 g (17.3 ml, 0.26 mol) of acrolein. When the
reaction was over (TLC), the mixture was subjected to
vacuum distillation. Yield of III 26 g (82%), bp 62
4 C (16 mm), n2 = 1.4876; published data [19]:
0
6
D
2
0
The IR spectra of XIVa and XIVb contain a band
bp 52.4 C (6 mm), n = 1.4883.
D
1
at 860 850 cm , which is typical of stretching vibra-
5
-Nitroethenylbicyclo[2.2.1]hept-2-ene (IV).
tions of the oxirane C O bond in epoxynorbornanes
16]. Also, absorption bands due to NH group (3350
310 cm ) and p-nitrophenylsulfonyl or p-nitroben-
zoyl substituent were present (Table 1).
The H NMR parameters of compounds XIVa and
XIVb are given in Table 4. In the region 3.05
.25 ppm we observed two doublets from protons of
the oxirane ring and a characteristic upfield signal
at 0.75 (0.80) ppm, belonging to one of the bridge
protons (anti-7-H). It is located above the oxirane ring
plane and is strongly shielded by the latter.
A solution of 6.2 g (0.154 mol) of sodium hydroxide
in 20 ml of an ice water mixture was added to
a mixture of 15 g (0.123 mol) of aldehyde III, 7.4 g
[
3
1
(
6.5 ml, 0.123 mol) of nitromethane, and 50 ml of
1
methanol at such a rate that the temperature did not
exceed 10 15 C (on cooling with ice NaCl). The
mixture was kept for 15 20 min, and 60 80 ml of
cold water containing crushed ice was added. The
resulting transparent solution was poured with stirring
into excess 20% hydrochloric acid, and the organic
phase (containing mainly nitro derivative IV) was
3
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 1 2002

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KAS’YAN et al.
Table 4. 1H NMR spectra of epoxynorbornanes XIVa and XIVb ( , ppm, J, Hz)
Comp.
no.
syn-7-H,
anti-7-H
NH,
Harom
1-H 2-H, 3-H 4-H 5-H
exo-6-H
endo-H
8-H , 8-H
9-H , 9-H
A B
A
B
XIVa 2.47 3.12, 3.06 2.35 1.92
1.75,
0.87
1.33, 0.75,
J7,7 = 9.6 J8,8 = 13.8,
1.67, 1.54,
3.02, 2.99,
J9,9 = 13.5 (NH)
4.94
2
3
3
2
2
2
J6,6 = 13.2,
J6,5 = 9.2,
J6,1 = 4.2
3
J8A,5 = 7.5,
J8B,5 = 8.4
8.36,
8.07
3
XIVb 2.51 3.24, 3.16, 2.47 1.98
1.84,
0.85,
1.36, 0.80,
J7,7 = 9.6 J8,8 = 13.8,
1.78, 1.66,
3.50, 3.47,
6.38
J9,9 = 13.5 (NH)
8.29,
3
2
3
3
3
2
2
2
J2,3 = 3.3
J6,6 = 11.7, J6,5 = 4.0,
J6,5 = 9.4,
J6,1 = 4.2
4
3
J6,7s = 2.0
J8A,5 = 6.6,
J8B,5 = 7.5
3
7.93
separated, dried, and distilled in vacuo. Yield 73%,
of p-nitrobenzoyl chloride in 10 ml of dry chloroform
was added dropwise with stirring to a mixture of
0.35 g (0.0026 mol) of amine II and 0.41 g (0.42 ml,
2
0
bp 107 108 C (5 mm), n = 1.5294; published data
D
2
0
[
12]: bp 102 104 C (0.6 mm), n = 1.5338.
D
0.0052 mol) of pyridine in 20 ml of dry chloroform.
5
-(2-Aminoethyl)bicyclo[2.2.1]hept-2-ene (II).
The mixture was stirred at room temperature until the
reaction was complete (TLC) and was then washed
with three portions of water, 20% hydrochloric acid,
and water again. The organic layer was separated and
dried over calcined magnesium sulfate, the solvent
was removed, and the product was recrystallized from
aqueous ethanol.
5-(2-Benzoylaminoethyl)bicyclo[2.2.1]hept-2-ene
(VIb) was synthesized in a similar way from 0.12 g
(0.9 mmol) of amine II and 0.12 g (0.9 mmol) of
benzoyl chloride.
A solution of 12 g (0.073 mol) of nitro derivative IV
in 20 ml of dry diethyl ether was added dropwise with
stirring to a suspension of 14 g (0.365 mol) of lithium
aluminum hydride in 100 ml of dry diethyl ether at
such a rate that the mixture moderately boiled. The
mixture was then stirred at 40 C until the reaction
was complete (TLC). Excess LiAlH4 was slowly
decomposed by adding moist diethyl ether and water,
the precipitate was filtered off, the organic phase was
separated and dried over calcined magnesium sulfate,
the solvent was distilled off, and the residue was
distilled under reduced pressure. Yield of amine II
5
-[2-(N -Benzylureido)ethyl]bicyclo[2.2.1]hept-2-
2
0
7
4%, bp 93 94 C (30 mm), n = 1.4976; published
D
ene (VIIa). Benzyl isocyanate, 0.15 g (0.0011 mol),
was added to a solution of 0.15 g (0.0011 mol) of
amine II in 2 ml of benzene. When the reaction was
complete, the crystals were filtered off, washed with
benzene, dried, and recrystallized from aqueous
ethanol (Tables 1 3). The same procedure was used
to synthesize compounds VIIb and VIII.
N-[2-(Bicyclo[2.2.1]hept-5-en-2-yl)ethyl]endic
imide (IX). Amine II, 0.1 g (0.73 mmol), was added
to a solution of 0.12 g (0.73 mmol) of endic anhydride
in 2 ml of benzene. The precipitate was filtered off,
washed with benzene, and recrystallized from aqueous
ethanol.
2
0
data [12]: bp 48 C (0.6 mm), n = 1.4985.
D
5
-[2-(p-Nitrophenylsulfonylamino)ethyl]bicyclo-
[
2.2.1]hept-2-ene (Va). A solution of 0.58 g
(0.0026 mmol) of p-nitrobenzenesulfonyl chloride in
10 ml of diethyl ether was added dropwise with stir-
ring to a mixture of 0.35 g (0.0026 mol) of amine II
and 0.51 g (0.42 ml, 0.0026 mol) of 20% aqueous
sodium hydroxide in 15 ml of diethyl ether. The mix-
ture was stirred until the reaction was complete
(
TLC), the solvent was removed, the residue was
dissolved in 20 ml of chloroform water (1:1), the
organic phase was separated, dried, and evaporated,
and the residue was recrystallized from aqueous
ethanol.
exo-2,3-Epoxy-5-[2-(p-nitrophenylsulfonyl-
amino)ethyl]bicyclo[2.2.1]heptane (XIVa). A mix-
ture of 0.15 g (0.47 mmol) of sulfonamide Va, 0.03 g
5
-[2-(p-Tolylsulfonylamino)ethyl]bicyclo[2.2.1]-
hept-2-ene (Vb) was synthesized in a similar way
from 0.15 g (0.0011 mol) of amine II and 0.21 g
(
0.47 mmol) of urea, 0.08 ml (0.94 mmol) of 35% hy-
drogen peroxide, and 0.14 g (0.94 mmol) of powdered
phthalic anhydride in 20 ml of chloroform was stirred
until the reaction was complete (TLC). The mixture
was neutralized with a saturated solution of sodium
(
0.0011 mol) of p-toluenesulfonyl chloride (Table 1).
-[2-(p-Nitrobenzoylamino)ethyl]bicyclo[2.2.1]-
hept-2-ene (VIa). A solution of 0.52 g (0.0028 mol)
5
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SYNTHESIS AND EPOXIDATION OF 5-(2-AMINOETHYL)BICYCLO[2.2.1]. . .
25
hydrogen carbonate, the organic layer was separated
and dried over calcined magnesium sulfate, the sol-
vent was removed, and the residue was purified by
chromatography on silica gel using diethyl ether as
eluent.
exo-2,3-Epoxy-5-[2-(p-nitrobenzoylamino)ethyl]-
bicyclo[2.2.1]heptane (XIVb) was synthesized in
a similar way (Tables 1, 4).
6. Kas’yan, A.O., Krishchik, O.V., Okovityi, S.I., and
Kas’yan L.I., Vopr. Khim. Khim. Tekhnol., 1998,
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7. Kasyan, L.I., Seljutin, O.B., Krasnovskaja, O.Yu.,
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1
995, p. 421.
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Podpletnjaja, H., Tarabara, I., and Krishchik, O.,
Fund. Clin. Pharmacol., 1999, vol. 13, no. 1, p. 377.
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