Synthesis of 2,4-disubstituted nortropinone derivatives by aldol condensation

Article abstract of DOI:10.1081/SCC-100106034

2,4-Disubstituted nortropinone derivatives 2, with anticipated anticonvulsant activity, were synthesized by the reaction of N-substituted nortropinones, ethanol, 5N-NaOH, and aromatic aldehydes (R₁CHO).

Full text of DOI:10.1081/SCC-100106034

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SYNTHESIS OF 2,4-DISUBSTITUTED NORTROPINONE
DERIVATIVES BY ALDOL CONDENSATION
Dai-Il Jung a , Chil-Sung Park b , Yong-Hwan Kim a , Do-Hun Lee a , Yong-Gyun Lee a , Yu-
Mi Park a & Soon-Kyu Choi a
a Department of Chemistry, Dong-A University, Pusan, 604-714, S. Korea
b Korea Research Institute of Chemical Technology, Taejon, 305-600, S. Korea
Version of record first published: 20 Aug 2006
To cite this article: Dai-Il Jung, Chil-Sung Park, Yong-Hwan Kim, Do-Hun Lee, Yong-Gyun Lee, Yu-Mi Park & Soon-
Kyu Choi (2001): SYNTHESIS OF 2,4-DISUBSTITUTED NORTROPINONE DERIVATIVES BY ALDOL CONDENSATION, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 31:21, 3255-3263
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SYNTHETIC COMMUNICATIONS, 31(21), 3255–3263 (2001)
SYNTHESIS OF 2,4-DISUBSTITUTED
NORTROPINONE DERIVATIVES BY
ALDOL CONDENSATION
Dai-Il Jung,1, Chil-Sung Park,2 Yong-Hwan Kim,1
*
Do-Hun Lee,1 Yong-Gyun Lee,1 Yu-Mi Park,1
and Soon-Kyu Choi1
1Department of Chemistry, Dong-A University,
Pusan 604-714, S. Korea
2Korea Research Institute of Chemical Technology,
Taejon 305-600, S. Korea
ABSTRACT
2,4-Disubstituted nortropinone derivatives 2, with anticipated
anticonvulsant activity, were synthesized by the reaction of
N-substituted nortropinones, ethanol, 5N-NaOH, and aro-
matic aldehydes (R1CHO).
Tropane alkaloids have received a great deal of attention because of
their remarkable pharmaceutical significance.1–4 Therefore a variety of syn-
thetic approaches to tropane alkaloids have been investigated. Especially, a
series of tropanes showed anticonvulsant activity against pentylenetetrazol-
induced convulsions in mice and antiarrhythmic activity in rabbit previously
treated with ouabain.5–8
*Corresponding author.
3255
Copyright & 2001 by Marcel Dekker, Inc.
www.dekker.com

ORDER
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3256
JUNG ET AL.
As a part of our study on the improvement of anticonvulsant agents,
herein we first report the synthesis of corresponding 2,4-disubstituted
nortropinones by aldol condensation from N-substituted nortropinones.
Earlier we reported the synthesis of N-substituted nortropinones derived
from the reaction of amine, 2,5-dimethoxytetrahydrofuran, and acetonedi-
carboxylic acid.9 2,4-Disubstituted nortropinones 2 were synthesized by
the reaction of N-substituted nortropinones 1, ethanol, 5N-NaOH and
aldehydes (R1CHO) (Scheme 1). The reaction mixture was stirred at room
temperature for the time interval indicated in Table 1. After the reaction
mixture was added to water, the precipitated solid was removed by filtra-
tion, and recrystallized first from n-hexane and EtOAc, and then from
ethanol. The yield, mp, IR, and 1H NMR of the products (2a–2m) are
summarized in Table 1 and reference.10 The aldol condensation of
1 provided only (2E, 4E)-2s. The stereochemical assignment of the double
bond (C-2 and C-4) of 2 was supported by NOE experiments. An NOED
spectrum showed an enhancement in the magnitude of the signal at d 7.83
(¼C-H, 2.39%), d 4.39 (C1H, 2.27%), and d 2.02 (H7a, 0.64%), respectively,
when the multiplet signal at d 7.35 (phenyl) was irradiated. And another
NOED spectrum showed an enhancement in the magnitude of the signal
d 2.02 (H7b, 18.14%) and d 7.35 (phenyl H, 4.65%), respectively, when the
signal at d 2.02 (H7a) was irradiated. Therefore, these NOE experiments
indicate 2E and 4E geometry.
Our attempt to prepare 2-substituted nortropinones 3 from N-
substituted nortropinones 1 was not successful, using various reaction
conditions; sodium hydride, or sodium methoxide, or butyl lithium.
Scheme 1.

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NORTROPINONE DERIVATIVES
3257
Table 1. Physical Data of 2,4-Disubstituted Nortropinone Derivatives

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REPRINTS
3258
JUNG ET AL.
A representative example for the synthesis of 2 follows: The mixture of
tropinone 1 (R¼CH3) (1.39 g, 1 Â 10À2 mol), ethanol (20 mL), 5N-NaOH
(2 mL) and benzaldehyde (1.6 g, 1.5 Â 10À2 mol) was stirred under N2 at
room temperature for 30 min. The mixture is poured into water (10 mL)
and the precipitated solid removed by filtration. The filtered solid was
recrystallized from n-hexane and EtOAc, and then from ethanol once
1
more to afford 2a in 57% yield. The H NMR spectrum (CDCl3, Me4Si)
showed a multiple H corresponding to the phenyl groups at d 7.25–7.44,
intergrating to 10 protons. The signals of the H-1 and H-5 clearly show at d
4.39 and the w ð1=2Þ value for the H-1(5) hydrogen signals of ꢀ10 Hz corre-
sponds to a tropane system with the piperidine ring in a flattened chain
conformation.8 Mass spectrum of 2a showed a molecular ion peak at m/z
315 (12%). Structures of all other products were confirmed by the same
manner as the 2a.
EXPERIMENTAL
Melting points were determined on an electrothermal capillary melting
point apparatus and uncorrected. TLC was performed on glass plates
coated with silicon oxide (silica gel 60F254) and compounds were visualized
using a uv lamp. Proton nuclear magnetic resonance and 13C NMR spectra
were obtained with Bruker AC 200 (200 MHz) and Varian Gemini (200 or
500 MHz) spectrometers. Mass spectra were measured with HP 5890II
GC/Mass (70 eV, EI). The organic solvents and chemicals were obtained
from commercial products and purified by the appropriate methods
before use.
Synthesis of (2E, 4E )-2,4-Dibenzylidene-8-methyl-8-aza-bicyclo[3.2.1]
octan-3-one 2a: 8-Methyl-8-aza-bicyclo[3.2.1]octan-3-one (1.39 g, 1 Â
10À2 mol) and benzaldehyde (1.6 g, 1.5 Â 10À2 mol) were added to ethanol
(20 mL) and 5N-NaOH (2 mL). The reaction mixture was stirred under N2
at room temperature for 30 min. The reaction mixture was diluted with
water (10 mL) and neutralized with 5% HCl. The precipitated solid was
removed by filtration. The filtered solid was recrystallized from n-hexane
and EtOAc, and then from ethanol once more to afford 2a (1.79 g) in 57%
yield. Rf : 0.21 (TLC eluent; n-hexane : EtOAc ¼ 10:1, v/v). mp 150–151ꢁC.
IR(n, KBr, cmÀ1): 3050, 2950, 1650 (C¼O), 1610, 1580, 1450, 1200.
1H NMR (CDCl3): d 7.83 (s, 2H), 7.44–7.25 (m, 10H), 4.39 (s, 2H), 2.31
(s, 3H), 2.60 (m, 2H), 2.02 (g, 2H). Mass, m/z (rel. intensity, %): 315 (12),
237 (100), 259 (29), 182 (12), 115 (20), 77 (10).
Synthesis of (2E,4E )-2,4-Bis-(4-Methoxy-benzylidene)-8-methyl-8-aza-
bicyclo[3.2.1]octan-3-one 2b: A mixture of 8-methyl-8-aza-bicyclo[3.2.1]

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NORTROPINONE DERIVATIVES
3259
octan-3-one (1.39 g, 1 Â 10À2 mol), anisaldehyde (2.04 g, 1.5 Â 10À2 mol),
ethanol (20 mL), and 5N-NaOH (2 mL) was stirred under N2 at room tem-
perature for 30 min. The reaction mixture was diluted with water (10 mL)
and neutralized with 5% HCl. The filtered solid was recrystallized from
n-hexane and EtOAc, and then from ethanol once more to afford 2b
(1.20 g) in 32% yield, Rf : 0.35 (TLC eluent ; n-hexane : EtOAc ¼ 10:1, v/v).
m.p. 162–163ꢁC. IR (n, KBr, cmÀ1): 2939, 2837, 1666 (C¼O), 1593, 1506,
1
1456, 1417, 1190. H NMR (CDCl3): d 7.37 (d, 4H), 6.95 (d, 4H), 4.41 (s,
2H), 3.85 (s, 6H), 2.61 (m, 2H), 2.50 (s, 3H), 2.01 (q, 2H). Mass, m/z (rel.
intensity, %): 375 (11), 247 (100), 332 (56), 288 (8), 145 (19), 115 (12), 63 (4).
Synthesis of (2E, 4E )-2,4-Bis-furan-2-ylmethylene-8-aza-bicyclo [3.2.1]
octan-3-one 2c: A mixture of 8-methyl-8-aza-bicyclo[3.2.1]octan-3-one
(1.39 g, 1 Â 10À2 mol), ethanol (20 mL), and 5N-NaOH (2 mL) was stirred
for 20 min. 2-Furaldehyde (1.44 g, 1.5 Â 10À2 mol) was added by using a
dropping funnel. The reaction mixture was stirred under N2 at room
temperature for 30 min. After stirring for 30 min, a crude light brown
solid was precipitated. The reaction mixture was diluted with water
(10 mL) and neutralized with 5% HCl. The filtered solid was recrystallized
from n-hexane and EtOAc, and then from ethanol once more to afford 2c
(1.51 g) in 51% yield. Rf : 0.30 (TLC eluent; n-hexane : EtOAc ¼ 1 : 1, v/v).
m.p. 134–135ꢁC. IR (n, KBr, cmÀ1): 3105, 2965, 1680 (C¼O), 1620, 1540,
1
1175. H NMR (CDCl3): d 7.58–7.57 (s, 2H), 7.45 (s, 2H), 6.66 (d, 2H),
6.53–6.50 (m, 2H), 4.83 (d, 2H), 2.53 (m, 2H), 2.43 (s, 3H), 1.79 (q, 2H)
Mass, m/z (rel. intensity, %): 295 (12), 267 (100), 238 (43), 210 (30), 175 (10),
116 (7), 77 (9).
Synthesis of (2E, 4E )-8-Methyl-2,4-bis-(1-methyl-1H-pyrrol-2-ylmethy-
lene-8-aza-bicyclo[3.2.1]octan-3-one 2d: A solution of 8-methyl-8-aza-bicyclo
[3.2.1]octan-3-one (1.39 g, 1 Â 10À2 mol), and 1-methyl-2-pyrrolecarboxal-
dehyde (1.64 g, 1.5 Â 10À2 mol) in ethanol (20 mL) added 5N-NaOH
(2 mL) was stirred. The reaction mixture was stirred under N2 at room
temperature for 12 h, diluted with water (10 mL) and neutralized with 5%
HCl. The filtered brown solid was recrystallized from n-hexane and EtOAc,
to afford 2d (0.73 g) in 23% yield. Rf : 0.34 (TLC eluent; n-hexane :
EtOAc ¼ 1 : 1, v/v). m.p. 173–173.5ꢁC. IR (n, KBr, cmÀ1): 3140, 2940,
1
1670 (C¼O), 1620, 1590, 1490, 1430, 1175. H NMR (CDCl3): d 7.77 (s,
2H), 6.83 (d, 2H), 6.46 (d, 2H), 6.25 (m, 2H), 4.49–4.45 (dd, 2H), 3.73 (s,
3CH3, 6H), 2.55 (m, 2H), 2.41 (s, 3H), 1.84 (q, 2H). Mass, m/z (rel. intensity,
%): 321 (12), 293 (100), 214 (8), 188 (8), 118 (10), 77 (5).
Synthesis of (2E, 4E)-2,4-Dibenzylidene-3-oxo-8-aza-bicyclo[3.2.1]oc-
tane-8-carboxylic acid ethyl ether 2e: 3-Oxo-8-aza-bicyclo[3.2.1]octane-8-
carboxylic acid ethyl ester (1.97 g, 1 Â 10À2 mol) and benzaldehyde (1.6 g,
1.5 Â 10À2 mol) were added to ethanol (20 mL) and 5N-NaOH (2 mL).

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3260
JUNG ET AL.
The reaction mixture was stirred under N2 at room temperature for 30 min.
After stirring for 30 min, a crude green solid was precipitated. The reaction
mixture was diluted with water (10 mL) and neutralized with 5% HCl.
The precipitated solid was removed by filtration. The filtered solid was
recrystallized twice from n-hexane and EtOAc to afford 2e (1.87 g) in 50%
yield. Rf : 0.26 (TLC eluent; n-hexane : EtOAc ¼ 5:1, v/v). m.p. 158–159ꢁC.
IR (n, KBr, cmÀ1): 3830, 3000, 1695 (C¼O), 1615, 1500, 1480, 1450,
1
1175. H NMR (CDCl3): d 7.75 (s, 2H), 7.45–7.39 (m, 10H), 5.44 (d, 2H),
3.99 (q, 2H), 2.53 (m, 2H), 2.05 (q, 2H), 1.08 (t, 3H). Mass, m/z (rel. intens-
tity, %): 373 (51), 345 (86), 317 (56), 272 (100), 243 (22), 115 (69), 77 (16).
Synthesis of (2E, 4E )-2,4-Bis-(4-methoxy-benzylidene)-3-oxo-8-aza-
bicyclo[3.2.1]octane-8-carboxylic acid ethyl ether 2f: A mixture of 3-oxo-8-
aza-bicyclo[3.2.1]octane-8-carboxylic acid ethyl ester (1.97 g, 1 Â 10À2 mol),
ethanol (20 mL) and 5N-NaOH (2 mL) was stirred for 20 min. Anisaldehyde
(2.04 g, 1.5 Â 10À2 mol), was added by using a dropping funnel. The reaction
mixture was stirred under N2 at room temperature for 30 min. After stirring
for 30 min, a crude green solid was precipitated. The reaction mixture was
diluted with water (10 mL) and neutralized with 5% HCl. The filtered solid
was recrystallized twice from n-hexane and EtOAc to afford 2f (2.17 g) in
50% yield. Rf : 0.28 (TLC eluent; n-hexane : EtOAc ¼ 5 : 1, v/v). m.p.
158–158.5ꢁC, IR (n, KBr, cmÀ1): 3140, 2940, 1670, 1620, 1590, 1490,
1430, 1175. 1H NMR (CDCl3): d 7.79 (s, 2H), 7.44–7.40 (dd, 4H),
6.98–6.93 (dd, 4H), 5.47 (d, 2H), 3.98 (q, 2H), 3.85 (s, 6H), 2. 54 (m, 2H),
2.05 (q, 2H), 1.05 (t, 3H). Mass, m/z (rel. intensity, %): 435 (20), 401 (40),
383 (100), 355 (17), 278 (11), 215 (1.8), 115 (43), 75 (19).
Synthesis of (2E, 4E )-2,4-Bis-furan-2-ylmethylene-3-oxo-8-aza-bicyclo
[3.2.1]octane-8-carboxylic acid ethyl ether 2g: A solution of 3-oxo-8-aza-
bicyclo[3.2.1]octane-8-carboxylic acid ethyl ester (1.97 g, 1 Â 10À2 mol)
and 2-furaldehyde (1.44 g, 1.5 Â 10À2 mol) in ethanol (20 mL) added
5N-NaOH (2 mL) was stirred. The reaction mixture was stirred under
N2 at room temperature for 30 min, diluted with water (10 mL) and neutra-
lized with 5% HCl. The filtered green solid was recrystallized twice from
n-hexane and EtOAc to afford 2g (1.77 g) in 50% yield. Rf : 0.29 (TÀL1C
eluent; n-hexane : EtOAc ¼ 1:1, v/v). m.p. 206–207ꢁC, IR (n, K Br, cm ):
3140, 3000, 1700 (C¼O), 1595, 1480, 1415, 1175. 1H NMR (CDCl3):
d 7.60 (s, 2H), 7.37 (s, 2H), 6.71 (d, 2H), 6.54–6.51 (m, 2H), 5.55 (m, 2H),
4.07 (q, 2H), 2.48 (m, 2H), 1.99 (q, 2H), 1.11 (t, 3H). Mass, m/z (rel.
intensity, %): 353 (40), 325 (63), 297 (30), 252 (10), 224 (19), 167 (11), 105
(15), 77 (19).
Synthesis of (2E, 4E )-2,4-Bis-(1-methyl-1H-pyrrol-2-ylmethylene)-3-
oxo-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid ethyl ether 2h: 3-Oxo-8-
aza-bicyclo[3.2.1]octane-8-carboxylic acid ethyl ester (1.97 g, 1 Â 10À2 mol)

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NORTROPINONE DERIVATIVES
3261
and 1-methyl-2-pyrrolecarboxaldehyde (1.6 g, 1.5 Â 10À2 mol) were added to
ethanol (20 mL) and 5N-NaOH (2 mL). The reaction mixture was stirred
under N2 at room temperature for 30 min. After stirring for 30 min, a crude
light brown solid was precipitated. The reaction mixture was diluted
with water (10 mL) and neutralized with 5% HCl. The precipitated solid
was removed by filtration. The filtered solid was recrystallized twice
from n-hexane and EtOAc to afford 2h (0.76 g) in 20% yield. Rf : 0.29
(TLC eluent; n-hexane : EtOAc ¼ 3:1, v/v). m.p. 206–206.5ꢁC. IR (n, KBr,
cmÀ1): 3020, 2960, 2900, 1690 (C¼O), 1595, 1450, 1175. 1H NMR (CDCl3):
d 7.63 (s, 2H), 6.84 (d, 2H), 6.55 (d, 2H), 6.28–6.25 (m, 2H), 5.53 (d, 2H),
4.04 (q, 2H), 3.73 (s, 6H), 2.51 (m, 2H), 1.93 (q, 2H), 1.15–1.08 (t, 3H).
Mass, m/z (rel. intensity, %): 379 (40), 351 (100), 278 (68), 246 (11),
118 (20), 77 (5).
Synthesis of (2E, 4E )-2,4-Dibenzylidene-8-phenyl-8-aza-bicyclo[3.2.1]
octan-3-one 2i: A mixture of 8-phenyl-8-aza-bicyclo[3.2.1]octan-3-one
(2.01 g, 1 Â 10À2 mol), ethanol (10 mL), methylene chloride (10 mL), and
5N-NaOH (2 mL) was stirred for 20 min. Benzaldehyde (1.6 g,
1.5 Â 10À2 mol) was added by using a dropping funnel. The reaction mixture
was stirred under N2 at room temperature for 3 h. After stirring for 3 h, a
crude brown solid was precipitated. The reaction mixture was diluted
with water (10 mL) and neutralized with 5% HCl. The filtered solid was
recrystallized twice from n-hexane and EtOAc to afford 2i (1.89 g) in 50%
yield. Rf : 0.34 (TLC) eluent; n-hexane : EtOAc ¼ 10 : 1, v/v). m.p.
222–223ꢁC. IR (n, KBr, cmÀ1): 3070, 2990, 1680 (C¼O), 1610, 1510,
1460. 1H NMR (CDCl3) : d 7.78 (s, 2H), 7.49–7.39 (m, 10H), 6.94 (t,
2H), 6.61 (s, 1H), 6.14 (dd, 2H), 5.24 (d, 2H), 2.73 (m, 2H), 2.27 (q, 2H).
Mass, m/z (rel. intensity, %) : 377 (40), 349 (100), 321 (15), 224 (10), 115
(16), 77 (21).
Synthesis of (2E, 4E )-2,4-Bis-furan-2-ylmethylene-8-phenyl-8-aza-bicy-
clo[3.2.1]octan-3-one 2j: A solution of 8-phenyl-8-aza-bicyclo[3.2.1]octan-3-
one (2.01 g, 1 Â 10À2 mol) and 2-furaldehyde (1.44 g, 1.5 Â 10À2 mol) in
ethanol (10 mL) and methylene chloride (10 mL) added 5N-NaOH (2 mL)
was stirred. The reaction mixture was stirred under N2 at room temperature
for 12 h, diluted with water (10 mL) and neutralized with 5% HCl. The
filtered brown solid was recrystallized twice from n-hexane and CH2Cl2 to
afford 2j (0.20 g) in 5.7% yield. Rf : 0.37 (TLC eluent; n-hexane:
EtOAc ¼ 5 : 1, v/v). m.p. 208–209ꢁC. IR (n, KBr, cmÀ1) : 3140, 2990, 1680
1
(C¼O), 1615, 1550, 1490. H NMR (CDCl3) : d 7.66 (2, 2H), 7.43 (s, 2H),
7.04 (t, 4H), 6.71–6.55 (m, 5H), 5.81 (d, 2H), 2.64 (m, 2H), 2.00 (q, 2H).
Mass, m/z (rel. intensity, %) : 375 (45), 329 (10), 300 (27), 272 (28), 237 (18),
115 (10), 77 (21).

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JUNG ET AL.
Synthesis of (2E, 4E )-2,4-Dibenxylidene-8-p-tolyl-8-aza-bicyclo[3.2.1]
octan-3-one 2k: 8-p-tolyl-8-aza-bicyclo[3.2.1]octan-3-one (2.15 g, 1 Â
10À2 mol) and benzaldehyde (1.6 g, 1.5 Â 10À2 mol) were added to ethanol
(10 mL), methylene chloride (10 mL), and 5N-NaOH (2 mL). The reaction
mixture was stirred under N2 at room temperature for 3.5 h. After stirring
for 3.5 h, a crude yellow solid was precipitated. The reaction mixture was
diluted with water (10 mL) and neutralized with 5% HCl. The precipitated
solid was removed by filtration. The filtered solid was recrystallized three
times form n-hexane and EtOAc to afford 2k (1.68 g) in 43% yield. Rf : 0.30
(TLC eluent; n-hexane : EtOAc ¼ 1 : 1, v/v,). m.p. 229–230ꢁC. IR (n, KBr,
cmÀ1) : 2959, 2837, 1672 (C¼O), 1605, 1493, 1446, 1160. 1H NMR
(CDCl3) : d 7.79 (s, 2H), 7.49–7.38 (m, 10H), 6.88 (dd, 2H), 6.02 (dd, 2H),
5.17 (d, 2H), 2.73 (m, 2H), 2.28 (q, 2H), 1.58 (s, 3H). Mass, m/z (rel. intensity,
%) : 411 (40), 383 (100), 355 (17), 215 (1.8), 115 (43), 75 (19).
Synthesis of (2E, 4E )-2,4-Dibenzylidene-8-(4-methoxy-phenyl)-8-aza-
bicyclo[3.2.1]octan-3-one 2l: A mixture of 8-(4-methoxy-phenyl)-8-aza-bicy-
clo[3.2.1]octan-3-one (2.31 g, 1 Â 10À2 mol), ethanol (10 mL), methylene
chloride (10 mL), and 5N-NaOH (2 mL) was stirred for 20 min.
Benzaldehyde (1.6 g, 1.5 Â 10À2 mol) was added by using a dropping
funnel. The reaction mixture was stirred under N2 at room temperature
for 30 min. After stirring for 30 min, a crude yellow solid was precipitated.
The reaction mixture was diluted with water (10 mL) and neutralized with
5% HCl. The filtered solid was recrystallized twice from n-hexane and
EtOAc to afford 2l (2.24 g) in 55% yield. Rf : 0.33 (TLC eluent;
n-hexane : EtOAc ¼ 1 : 1, v/v). m.p. 228–229ꢁC. IR (n, KBr, cmÀ1): 3070,
1
3000, 1690 (C¼O), 1610, 1520, 1475. H NMR (CDCl3) : d 7.78 (s, 2H),
7.50À7.40 (m, 10H), 6.53 (dd, 2H), 6.10 (dd, 2H), 5.17 (d, 2H), 3.63 (s,
3H), 2.73 (m, 2H), 2.25 (q, 2H). Mass, m/z (rel. intensity, %) : 4.7 (74),
379 (100), 351 (20), 274 (10), 215 (7), 115 (14), 77 (17).
Synthesis
of
(2E, 4E )-2,4-Bis-furan-2-ylmethylene-8-(4-methoxy-
phenyl) -8-aza-bicyclo[3.2.1]octan-3-one 2m: A solution of 8-(4-methoxy-
phenyl)-8-aza-bicyclo[3.2.1]octan-3-one (2.31 g, 1 Â 10À2 mol) and 2-furalde-
hyde (1.44 g), 1.5 Â 10À2 mol) in ethanol (10 mL) and methylene chloride
(10 mL) added 5N-NaOH (2 mL) was stirred. The reaction mixture was
stirred under N2 at room temperature for 30 min, diluted with water
(10 mL) and neutralized with 5% HCl. The filtered brown solid was recrys-
tallized twice from n-hexane and EtOAc to afford 2m (2.09 g) in 54% yield.
Rf : 0.23 (TLC eluent; n-hexane) : EtOAc ¼ 5 : 1, v/v). mp 175–176ꢁC. IR
(n, KBr, cmÀ1): 3250, 3120, 1680 (C¼O), 1600, 1540, 1440, 1H NMR
(CDCl3) : d 7.66 (s, 2H), 7.26 (s, 1H), 6.71–6.55 (m, 10H), 5.76 (d, 2H),
3.65 (s, 3H), 2.65 (m, 2H), 1.98 (t, 2H). Mass, m/z (rel. intensity, %) : 387
(70), 359 (100), 330 (33), 267 (13), 134 (10), 105 (17), 77 (21).

ORDER
REPRINTS
NORTROPINONE DERIVATIVES
3263
ACKNOWLEDGMENT
The work was supported in part by a grant of Dong-A University
(1999) and in part by a grant of the 97’ Good Health R D project (HMP-
96-D-1-0001), Ministry of Health and Welfare.
REFERENCES
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Received in the USA January 21, 2001

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