Synthesis of substituted tricyclo[5.3.1.04,9]undecan-2,6-diones

Article abstract of DOI:10.1016/S0040-4020(01)00172-7

The morpholine enamines of 4-acetyl-4-phenylcyclohexanone 3a, 4-acetyl-4-isopropenylcyclohexanone 3b, 4-acetyl-4-methylcyclohexanone 3c react with acryloyl chloride to give 1-phenyl-4(N-morpholino)tricyclo[5.3.1.0^4,9]undecan-2,6-dione 9a, 1-isopropenyl-4(N-morpholino)tricyclo[5.3.1.0^4,9]undecan-2,6-dione 9b, and 1-methyl-4(N-morpholino)tricyclo[5.3.1.0^4,9]undecan-2,6-dione 9c, respectively, along with the corresponding substituted adamantane-2,4-diones. The morpholine enamine of 4-acetyl-4-benzylcyclohexa-none 3d and pyrrolidine enamine of 4-acetyl-4-phenylcyclohexanone 3a yield the corresponding 1-benzyl-4(N-morpholino)tricyclo[5.3.1.0^4,9]undecan-2,6-dione 9d and 8(R)-methyl-1-phenyl-4(N-pyrrolidinyl)tricyclo[5.3.1.0^4,9] undecan-2,6-dione 9e. No substituted adamantane-2,4-diones were formed in any of the latter two reactions.

Full text of DOI:10.1016/S0040-4020(01)00172-7

TETRAHEDRON
Pergamon
Tetrahedron 57 02001) 3143±3150
Synthesis of substituted tricyclo[5.3.1.04,9]undecan-2,6-diones
M. Giasuddin Ahmed,a,p Syed M. Iqbal Moeiz,a S. Asghari Ahmed,a Fumiyuki Kiuchib
and Yoshisuke Tsudac
aDepartment of Chemistry, University of Dhaka, Dhaka 1000, Bangladesh
bDepartment of Pharmacognosy, Graduate School of Pharmaceutical Science, Kyoto University, Yoshida, Sakyo-Ku, Kyoto 606-8501, Japan
cFaculty of Pharmaceutical Sciences, Kanazawa University, 13-1 Takara-Machi, Kanazawa 920, Japan
Received 29 June 2000; revised 16 January 2001; accepted 1 February 2001
AbstractÐThe morpholine enamines of 4-acetyl-4-phenylcyclohexanone 3a, 4-acetyl-4-isopropenylcyclohexanone 3b, 4-acetyl-4-methyl-
cyclohexanone 3c react with acryloyl chloride to give 1-phenyl-40N-morpholino)tricyclo[5.3.1.04,9]undecan-2,6-dione 9a, 1-isopropenyl-
40N-morpholino)tricyclo[5.3.1.04,9]undecan-2,6-dione 9b, and 1-methyl-40N-morpholino)tricyclo[5.3.1.04,9]undecan-2,6-dione 9c, respect-
ively, along with the corresponding substituted adamantane-2,4-diones. The morpholine enamine of 4-acetyl-4-benzylcyclohexa-none 3d and
pyrrolidine enamine of 4-acetyl-4-phenylcyclohexanone 3a yield the corresponding 1-benzyl-40N-morpholino)tricyclo[5.3.1.04,9]undecan-
2,6-dione 9d and 80R)-methyl-1-phenyl-40N-pyrrolidinyl)tricyclo[5.3.1.04,9]undecan-2,6-dione 9e. No substituted adamantane-2,4-diones
were formed in any of the latter two reactions. q 2001 Published by Elsevier Science Ltd.
We had reported1±3 previously a substituted tricyclo
[5.3.1.04,9]undecan-2,6-dione 9c which we had isolated
from the reaction of the morpholine enamine of 4-acetyl-
4-methylcyclohexanone 3c with acryloyl chloride. We now
herein report the synthesis of four new substituted tricyclo
[5.3.1.04,9]undecan-2,6-diones: 9a, 9b, 9d and 9e. The
tricyclo[5.3.1.04,9]undecane system has not been reported
previously. The synthesis is based on a general reaction of
4,4-disubstituted cyclohexanone enamines with a,b unsatu-
rated acid chlorides. We ®rst prepared 4,4-disubstituted
cyclohexanones 3a±c following literature methods4,5 in
which one of the substituents is an acetyl group 0Scheme 1).
4-Acetyl-4-benzylcyclohexanone 3d was prepared 0Scheme
1) following the procedure described in Section 1. The
morpholine enamines 4a±d and the pyrrolidine enamine 4e
were prepared 0Scheme 1) in accordance with the general
procedure reported earlier2,3 without using any catalysts.
acryloyl chloride with morpholine enamines of 3a and 3b
followed similar routes as that of 3c yielding the compounds
9a 011%) and 9b 018%), respectively, in addition to the
corresponding substituted adamantane-2,4-diones which
we have reported previously.1,2 On the contrary, the
morpholine enamine of 3d gave only the compound 9d
033%) in its reaction with acryloyl chloride without pro-
ducing any adamantane structures. The reaction of pyrro-
lidine enamine of 3a with crotonoyl chloride yielded in a
similar manner only the compound 9e 022%) and none of the
adamantane derivatives although the morpholine enamine
of the same ketone 3a reacted with crotonoyl chloride to
give only the corresponding adamantane-2,4-dione and no
substituted tricyclo[5,3,1,04,9]undecan-2,6-diones which we
reported earlier1.
The general reaction between a,b-unsaturated acid chlor-
ides and 4,4-disubstituted cyclohexanone enamines may be
shown to follow the mechanistic pathways 0Scheme 2)
yielding either substituted adamantane-2,4-diones or sub-
stituted tricycloundecane-2,6-diones or a mixture of both
as products. The formation of adamantane-2,4-diones
reported1±3 earlier has been explained through the formation
of the intermediate enolate anion 012) which cyclises onto
the axially orientated acetyl group. When the acetyl group is
in an equatorial conformation it may give rise to an alter-
native enolate anion 08) 0preferably twist form) which
would lead to the formation of the tricycloundecane-2,6-
dione structure by cyclisation onto the iminium carbon.
This mechanism has been reported3 by us previously for
the formation of 9c. As each of the reactions of 4a±c with
acryloyl chloride yield both the adamantanediones and
In our earlier report3 we had found that the reaction of
morpholine enamine of 4-acetyl-4-methylcyclohexanone
3c with acryloyl chloride yielded a mixture of 9c and 6,7-
dimethyl-6-hydroxyadamantane-2,4-dione. At that time, we
could not isolate them in the pure form from the mixture. In
the present work we have separated the compound 9c 030%)
completely from the adamantane product. The reactions of
Keywords: morpholine; pyrrolidine; 4,4-disubstituted cyclohexanone;
enamine; acryloyl chloride; substituted adamantane-2,4-dione; substituted
tricyclo [5.3.1.04,9]undecan-2,6-dione.
p
Corresponding author. Fax: 1880-2-8615583;
e-mail: mgahmed@bangla.net
0040±4020/01/$ - see front matter q 2001 Published by Elsevier Science Ltd.
PII: S0040-4020001)00172-7

3144
M. G. Ahmed et al. / Tetrahedron 57 42001) 3143±3150
Scheme 1.
tricycloundecanes, it is evident that the substituent Y is
equatorial in the enolate anion 012) and is axial in the
enolate anion 08). In a similar way it may be inferred that
the reactions of 4d with acryloyl chloride and 4e with cro-
tonoyl chloride occur mostly through the formation of the
enolate anion 08) where the substitutent Y is axial and the
acetyl group is equatorial since no adamantanediones were
isolated from these reactions.
In the present work we have reinvestigated the structure of
the compound 9c in more detail with the help of its 1H and
1
13C NMR, H±1H NMR COSY, 13C±1H NMR COSY and
mass spectral data. The structures of the compounds 9a, 9b,
1
9d and 9e were con®rmed by their elemental analysis, H
and 13C NMR and mass spectroscopic methods. All the
protons and carbons of these compounds were assigned by
analogy with those of the compound 9c. Preparation and char-
acterisation of the dioxime derivatives of the compounds 9b,
9c and 9d gave additional evidence for their structures 0see
Section 1). In addition to the spectral data the structure of 9e
was further con®rmed with the help of its X-ray analysis
0Fig. 1).
As shown in Scheme 3 the steric interaction due to the
axially orientated substituent X or Y would be a minimum
in the ketene or enolate anion where R0 is H which means
acryloyl chloride. This explains why tricycloundecane-
diones 9a±c are obtained along with the corresponding
adamantanediones from the reactions of the enamines
4a±c with acryloyl chloride and not with any other acid
chloride. The explanation of the formation of 9d as the
predominant product in the reaction of 4d with acryloyl
In the 1H NMR spectra 0Table 1) the equivalent CH2±O±CH2
methylene protons of the morpholine moiety of the
compounds 9a±d appeared as a triplet at the lowest ®eld
at d 3.60±3.65 030 and 50 protons) with coupling constant of
4.45±4.70 Hz. On the other hand 20 and 60 protons which
are a to the nitrogen atom and also 20 and 50 protons 0a to
the nitrogen atom) of the pyrrolidine moiety in 9e appeared
as a multiplet 0Table 1); the nonequivalence of these protons
arising is probably due to different spatial arrangements next
to the cage structure. The coupling pattern of the methylene
and methine protons were ascertained clearly with different
J values 0which was not done in the previous report3 of 9c).
The methylene protons at position 3 gave two doublets
018.7 Hz). The axial protons at positions 3 and 7 are more
deshielded than the equatorial protons due to the adjacent
carbonyl groups. At position 3 the axial proton also receives
steric shielding from the adjacent morpholino group
1
chloride is provided by the H±1H COSY NMR spectral
data of the starting 4-acetyl-4-benzylcyclohexanone 3d
which show that the substituent benzyl group is predomi-
nantly axial. The production of the tricycloundecanedione
9e without any adamantanedione formation may be attrib-
uted to the greater reactivity of the iminium carbon bonded
to nitrogen of the pyrrolidine ring onto which the enolate
anion 08) cyclizes 0Scheme 2). This greater reactivity prob-
ably outweighs the repulsive interaction due to the axially
orientated phenyl group in the enolate anion 0Scheme 3)
where R0 is methyl group. The stereochemistry of 8-CH3
group having R con®guration in 9e is based on the formation
of the favoured ketene 0Scheme 3).

M. G. Ahmed et al. / Tetrahedron 57 42001) 3143±3150
3145
Scheme 2.
0position 4) that is equatorial. The overall effect is that 3-Ha
is more up®eld by 0.11±0.12 ppm than 3-He. Of the
alicyclic part, the most down®eld proton is at the bridge-
head position as it is ¯anked by a carbonyl group and the
morpholino group. 8-Ha is deshielded more than 8-He by
0.57±0.66 ppm due to the anisotropic effect of carbonyl
group at position 6. At both the positions 10 and 11 the
axial protons are more up®eld than the equatorial
protons, 0.30±0.53 ppm in the case of protons at 10-C
and 0.20±0.41 ppm in the case of protons at 11-C, prob-
ably due to the anisotropic effect of the substituents at
position 1.
showed the J values as 14.2±14.9 Hz and 13.2±13.9 Hz,
respectively. The large J value of 9.0 Hz in 9e and
11.9±12.1 Hz in the cases of other tricycloundecanediones
were observed for vicinal coupling between 5-H and 11-He.
The vicinal coupling between 9-H and 10-He also showed a
large coupling constant of 11.7±11.9 Hz.
In 13C NMR spectra 0Table 3), the two carbonyl carbons at
positions 2 and 6 resonated at the lowest ®eld. 2-C Shifted
further down®eld as compared to 6-C probably due to
substitution at the adjacent carbon at position 1. As expected
the equivalent 20 and 50 carbons in 9e and 20 and 60 carbons
in 9a±d a to the nitrogen atom, resonated at d 49.45 and at
44.69±45.10 respectively, whereas 30 and 50 carbons a to
The coupling constants are shown in Table 2. The geminal
couplings between 10-Ha and 10-He and 11-Ha and 11-He

3146
M. G. Ahmed et al. / Tetrahedron 57 42001) 3143±3150
Scheme 3.
the oxygen atom resonated at d 67.07±67.39 in the
compounds 9a±d.
1. Experimental
1.1. General
The 1-CH3 carbon in the case of 9c was at the highest ®eld
0d 19.21). Of the ring carbons the quaternary 1-C and 4-C
gave less intense peaks and 4-C was deshielded signi®cantly
at d 62.28±62.74 due to the electron withdrawing morpho-
lino and pyrrolidinyl groups.
1H and 13C NMR spectra were recorded on a JEOL 400
instrument at the School of Pharmaceutical Sciences,
Kanazawa University. A number of NMR spectra were
recorded on a General Electric 300 NMR spectrometer at
the department of Chemistry, Kent State University. Low-
resolution mass spectra were run at the department of
Chemistry, George Mason University using a Finnigan
Mat Mass Spectrometer and the high-resolution mass
spectra were recorded in Kanazawa University. Melting
points were determined in open-ended capillary tubes
As expected, the 7-C was deshielded more by 5.03±
5.79 ppm than 8-C due to adjacent carbonyl group at 6
position. 9-C was deshielded more than 8-C by 5.74 ppm
in 9e and by 4.37±4.60 ppm in the other compounds due to
the fully substituted bridgehead carbon 4-C. Of 7-C, 8-C,
9-C, 10-C and 11-C the carbon at 10-C resonated most
down®eld. Besides other factors, the reason for this may
be attributed to the g-anti effect6 which indicates that Ca
011-C), Cb 01-C) and Cg 02-C doubly substituted by O) are
compressed in the same plane.6 3-C gave the expected
down®eld shift due to the adjacent 02-C) carbonyl group
and fully substituted 4-position. 5-C is more deshielded
than 3-C by 6.95 ppm in 9e and by 7.91±8.98 ppm in the
other compounds.
1
and are uncorrected. All H and 13C NMR spectra were
recorded in CDCl3 if not otherwise mentioned. IR spectra
were run as KBr pellets in the case of solids and solution
in the case of liquids; absorptions are expressed in cm21
.
For column chromatography silica gel 100 0supplied by E.
Merck) and light petroleum 060±808)/chloroformˆ10:1
were used.
1.1.1. Preparation of 4,4-disubstituted cyclohexanones.

M. G. Ahmed et al. / Tetrahedron 57 42001) 3143±3150
3147
Figure 1. ORTEP stereospeci®c view of 09e).
1
Table 1. H NMR spectral data of the tricycloundecanediones 9a, 9b, 9c, 9d and 9e 0chemical shifts in d and coupling constants J in Hz)
Protons
9a
9b
9c
9d
9e
3-Ha
2.42
2.53
3.03
2.74
2.50
2.32
1.70
2.53
1.98
2.28
1.58
2.09
2.28
2.40
2.92
2.75
2.43
2.28
1.62
2.45
1.68
2.21
1.60
1.80
2.24
2.35
2.87
2.76
2.28
2.20
1.63
2.39
1.70
2.03
1.60
1.87
2.26
2.38
2.85
2.80
2.33
2.16
1.58
2.37
1.63 0m)
1.94 0m)
1.55
1.78 0m)
2.43±2.56
0m)
2.47
2.59
2.94
2.87
2.50
2.25
±
2.61
1.92
2.42
2.20
2.08
±
3-He
5-H
7-Ha
7-He
8-Ha
8-He
9-H
10-Ha
10-He
11-He
11-He
20,60-H2
Morpholino
30,50-H2
Morpholino
1-C6H5
1-C±Hc
1-C±Ht
1-C±CH3
1-CH2C6H5
1-CH2C6H5
1-CH3
2.65±2.57
0m)
2.60±2.47
0m)
2.45±2.60
0m)
3.65
0t, Jˆ4.50)
3.63
0t, Jˆ4.45)
3.63
0t, Jˆ4.70)
3.60
0t, Jˆ4.50)
±
7.39±7.16
±
4.75
±
±
±
±
7.41±7.15
±
±
±
±
±
±
±
±
±
±
±
5.02
1.77 0s)
±
±
±
±
±
±
1.03
±
2.81 0s)
7.1±7.29 0m)
±
20,50-H2
Pyrrolidinyl
30,40-H2
Pyrrolidinyl
8-CH3
2.83±2.70
0m)
1.68
±
±
±
±
±
±
0t, Jˆ5.50)
1.34

3148
M. G. Ahmed et al. / Tetrahedron 57 42001) 3143±3150
Table 2. Coupling constants 0J in Hz) of the tricycloundecandiones 9a, 9b,
9c, 9d and 9e
crystals of 4-acetyl-4-benzylpimelonitrile 01d) were
obtained, yield 75.5 g, 60%, mp 74±758C; IR nmax 2248
0CuN), 1685 0CvO), 1615, 1595 0CvC of phenyl);
Protons
9a
9b
9c
9d
9e
1
d[DMSO] H NMR: 7.30±7.07 0m, 5H, aromatic protons),
3-Ha, 3-He
5-H, 11-Ha
5-H, 11-He
7-Ha, 7-He
8-Ha, 8-He
9-H, 10-Ha
9-H, 10-He
10-Ha, 10-He
10-He, 11-He
11-Ha, 11-He
8-Ha, 8-CH3
18.7
±
11.9
±
12.8
3.6
11.7
14.6
3.0
13.2
±
18.7
±
12.1
±
12.0
3.7
±
14.4
±
18.7
3.8
12.1
18.7
15.8
4.1
11.8
14.2
3.4
14.7
±
18.7
3.6
12.0
±
18.7
4.5
9.0
11.0
±
2.9
±
14.9
4.5
14.5
7.2
2.90 0s, 2H, CH2C6H5), 2.56±2.49 0m, 2H, one CH2±CN),
2.45±2.38 0m, 2H, another CH2±CN),1.93±1.87 0m, 2H,
one CH2±CH2±CN), 1.82±1.76 0m, 2H, another
CH2±CH2±CN), 2.20 0s, 3H, COCH3); 13C NMR: 210.03
0CvO and CuN), 136.02, 129.66, 128.21, 126.69, 120.40
±
4.0
11.9
14.2
3.4
14.9
±
0aromatic carbons), 54.12 0
), 39.09 0CH2C6H5), 27.44
0CH2±CN), 26.37 0CH2±CH2±CN), 11.49 0COCH3); MS m/
z 254 0M1), 200, 131, 128, 115, 91, 77, 65, 44, 43, 28. Anal.
Calcd for C16H18N2O: C, 75.59%; H, 7.08%; N, 11.02%.
Found: C, 75.47%; H, 7.14%; N, 10.92%.
13.3
±
1.1.3. 4-Acetyl-4-benzylpimelic acid *2d). A mixture of
4-acetyl-4-benzylpimelonitrile 01d) 060 g, 0.23 mol), potas-
sium hydroxide 033.13 g, 0.59 mol) and water 0350 mL) was
heated to re¯ux for 24 h. The hot solution was treated with
activated charcoal and ®ltered hot. The ®ltrate was then
cooled. 4-Acetyl-4-benzylpimelic acid 02d) was precipi-
tated on acidi®cation of the ®ltrate with concentrated hydro-
chloric acid at room temperature 0308C). The precipitated
acid after recrystallisation from boiling water gave colour-
less crystals. Yield 58.07 g, 84%, mp 114±158C; IR nmax
3500 0OH), 1715, 1700 0CvO), 1615, 1595 0CvC of
phenyl); d[DMSO] 1H NMR: 12.10 0br s, 2£COOH),
7.27±7.04 0m, 5H, aromatic protons), 2.85 0s, 2H,
CH2C6H5), 2.18±2.08 0m, 4H, 2£CH2COOH), 1.79±1.66
0m, 4H, 2£CH2CH2COOH), 2.14 0s, 3H, COCH3); 13C
NMR: 211.55 0COCH3), 174.07 0COOH), 137.02, 130.43,
129.72, 128.06, 127.80, 126.37 0aromatic carbons), 53.88
4-Acetyl-4-phenylcyclohexanone 03a)4, 4-acetyl-4-isopro-
penylcyclohexanone 03b)5, 4-cetyl-4-methylcyclohexanone
03c)5 and their precursors 01a)4, 02a)4, 01b)7, 02b)8, 01c)4 and
02c)4 were prepared by following the literature methods
0Scheme 1). 4-Acetyl-4-benzylcyclohexanone 03d) and its
precursors 01d) and 02d) were prepared in the following way
0Scheme 1).
1.1.2. 4-Acetyl-4-benzylpimelonitrile *1d). Acrylonitrile
053.0 g, 1 mol) was added dropwise to a mechanically
stirred solution of benzylacetone 073.5 g, 0.50 mol), 30%
potassium hydroxide solution in methanol 05 mL) and
tert-butanol 0100 mL) over 3h maintaining the temperature
of the reaction mixture at 3±68C by ice cooling. After the
addition was complete, the reaction mixture was stirred for
1 h more. The crystalline solid formed was ®ltered off,
washed with a mixture of tert-butanol and ethanol 08:1)
and dried. Upon recrystallisation from ethanol colourless
0
), 39.50 0CH2C6H5), 28.52 0CH2COOH), 27.60
0CH2CH2COOH), 26.24 0COCH3); MS m/z 2920M1), 232,
Table 3. 13C NMR spectral data of the compounds 9a, 9b, 9c, 9d and 9e 0chemical shifts in d)
9a
9b
9c
9d
9e
48.88
1-C
2-C
3-C
4-C
5-C
6-C
7-C
8-C
48.46
49.33
211.76
39.32
62.41
47.23
210.48
30.19
25.12
29.51
32.48
30.31
44.82
67.13
41.50
212.63
38.74
62.74
47.72
211.93
30.50
25.34
29.80
35.99
33.59
44.99
67.36
44.82
211.56
39.40
62.34
47.59
210.11
30.23
25.20
29.88
34.44
32.23
44.89
67.17
212.06
38.31
62.28
47.14
212.00
30.14
25.00
29.37
32.91
30.61
44.69
67.07
212.52
44.85
62.65
51.80
211.12
37.87
32.08
37.82
39.20
38.23
9-C
10-C
11-C
2060-C2 0Morpholino)
3050-C2 0Morpholino)
2050-C2 0Pyrrolidinyl)
3040-C2 0Pyrrolidinyl)
1-C±C6H5
49.45
23.34
139.40 01-C)
128.07 02-C)
127.05 01-C)
126.87 02-C)
138.71 01-C
128.12 02-C)
127.20 01-C)
126.97 02-C)
1-C±C0CH3)vCH2
1-C±C0CH3)vCH2
1-C±C0CH3)vCH2
1-C±CH3
144.20
112.78
20.51
19.21
1-C±CH2C6H5
1-C±CH2C6H5
38.95
136.80 01-C)
130.41 02-C)
127.94 02-C)
126.26 01-C)
8-C±CH3
22.70

M. G. Ahmed et al. / Tetrahedron 57 42001) 3143±3150
3149
213, 185, 141, 128, 91, 65, 55. Anal. Calcd for C16H20O5:
C,65.75%, H,6.84%. Found: C,65.79%; H,6.92%.
1.3. Synthesis of 1-phenyl-4*N-morpholino)tricyclo
[5.3.1.04,9]undecan-2,6-dione *9a), 1-isopropenyl-4*N-
morpholino)tricyclo[5.3.1.04,9]undecan-2,6-dione*9b),
1-methyl-4*N-morpholino)tricyclo [5.3.1.04,9]undecan-
2,6-dione *9c) and 1-benzyl-4*N-morpholino) tricyclo
[5.3.1.04,9]undecan-2,6-dione *9d)Ðgeneral method
1.1.4. 4-Acetyl-4-benzylcyclohexanone *3d). A mixture of
4-Acetyl-4-benzylpimelic acid 02d) 020.0 g, 68.0 mmol),
freshly distilled acetic anhydride 020.92 g, 0.2 mol) and
pyridine 06.2 mL) was heated to re¯ux for 2 h. The acetic
acid formed, the excess acetic anhydride and pyridine left in
the reaction mixture were removed by distillation at atmos-
pheric pressure. The remaining viscous mass was then
distilled under reduced pressure to give a colourless liquid
of 4-acetyl-4-benzylcyclohexanone 03d), yield 9.22 g, 61%;
bp 190±2008C/2 mmHg.; IR nmax 0liquid ®lm) 1695 0broad,
Acryloyl chloride 020.55±29.0 mmol) in dry benzene 040±
45 mL) was added dropwise to a boiling solution of the
morpholinoenamine 020.52±28.6 mmol) in dry benzene
0130±170 mL) during 2 h. During the addition a solid was
slowly precipitated from the reaction mixture. The mixture
was then heated under re¯ux with stirring for 20 h, cooled
and the precipitated iminium salt was ®ltered off and
washed with dry benzene. The solid thus collected was
hydrolysed by stirring with ice cold water 050 mL) for
10 h and ®nally extracted with ether 05£25 mL). The sepa-
rated aqueous layer was further extracted with chloroform
05£25 mL). The crude tricyclic compounds were isolated
from the extracts and puri®ed by separation from adaman-
tanediones by fractional recrystallisation in the case of 09a)
from chloroform and light petroleum 040±608C) and with
the help of column chromatography in the case of 09b) and
09c) while the column was packed with silica gel and was
eluted initially with light petroleum 060±808C) and the
gradual addition of chloroform. The compound 09d) was
puri®ed by recrystallisation from chloroform and light
petroleum 040±608C). The following results were obtained:
1
CvO), 1625, 1615, 1595 0CvC, phenyl); d[CDCl3] H
NMR: 7.29±7.03 0m, 5H, aromatic protons), 2.87 0s, 2H,
CH2C6H5), 2.39±2.32 0m, 2,6-H2 eq), 2.32±2.25 0m, 3,5-H2
eq) 1.77±1.69 0m, 3,5-H2 ax and 2,6-H2 ax), 2.23 0s, 3H,
COCH3); 13C NMR 211.05 0C-1), 210.37 0COCH3), 135.77,
129.76, 128.25, 126.95 0aromatic carbons), 52.49 0C-4),
44.55 0CH2C6H5), 38.15 0C-2 and C-6), 32.41 0C-3 and
C-5) and 25.68 0COCH3), and. MS m/z 2300M1), 139,
128, 115, 91, 77, 55, 43. HRMS Calcd for C15H18O2 0M1)
230.1306; found 230.1281.
1.2. Preparation of enaminesÐgeneral method
A mixture of the 4,4-disubstituted cyclohexanone 020.83±
29.0 mmol) and a slight excess of morpholine or pyrrolidine
021.83±32.20 mmol) in benzene 075±80 mL) was heated to
re¯ux under a Dean and Stark head for 12±16 h. On cooling,
the solvent and the excess of amine were removed under
reduced pressure 0by rotary evaporator) and the crude
enamine was used without further puri®cation since exten-
sive decomposition occured on distillation. The following
enamines were prepared:
Acryloyl chloride reacting with 04a) gave an 11% yield of
09a) 00.80 g) which was puri®ed by recrystallisation from
chloroform and light petroleum 040±608C) and obtained as
colourless needles, mp 215±168C, Rf 0chloroform and ethyl
acetate, 6:1) 0.52; IR nmax 1725, 1698 0CvO), 1665, 1595
0CvC). MS m/z 339 0M1), 338, 311, 297, 296, 253, 194,
165, 115, 56, 40. HRMS Calcd for C21H25NO3 0M1)
339.1834; found 339.1837.
Acryloyl chloride reacting with 04b) gave an 18% yield of
09b) 01.65 g) which was puri®ed with the help of column
chromatography and obtained as colourless plates, mp 215±
168C, Rf 0chloroform and ethyl acetate, 4:1) 0.50; IR nmax
1695 0broad CvO), 1635 0CvC). MS m/z 303 0M1), 275,
261, 260, 217, 192, 166, 57. Anal. Calcd for C18H25NO3: C,
71.28%, H, 8.25%, N, 4.62%. Found: C, 71.38;H, 8.35%; N,
4.62%. C, 75.81; H, 7.04%.
1.2.1. 4-Acetyl-4-phenyl-1-morpholinocyclohexene *4a).
Light yellow viscous mass, IR nmax: 1700 0sharp, CvO of
acetyl), 1638 0CvC).
1.2.2. 4-Acetyl-4-isopropenyl-1-morpholinocyclohexene
*4b). Light brown viscous mass, IR nmax: 1700 0sharp,
CvO), 1655, 1638 0CvC).
Acryloyl chloride reacting with 04c) gave a 30% yield of
09c) 02.41 g) which was puri®ed with the help of column
chromatography and obtained as colourless plates,mp 192±
1938C, Rf 0chloroform and ethyl acetate, 5:1) 0.36; IR nmax
1698 0broad CvO), 1638 0CvC). MS m/z 277 0M1), 275,
261, 249, 235, 234, 191, 166, 57. Anal. Calcd for C16H23NO3:
C, 69.30%, H, 8.30%; N, 5.10%. Found: C, 69.20; H, 8.70%;
N, 5.10%.
1.2.3. 4-Acetyl-4-methyl-1-morpholinocyclohexene *4c).
Light brown viscous mass, IR nmax: 1700 0sharp, CvO),
1638 0CvC).
1.2.4. 4-Acetyl-4-benzyl-1-morpholinocyclohexene *4d).
Light yellow viscous mass, IR nmax: 1700 0sharp, CvO),
1638 0CvC).
Acryloyl chloride reacting with 04d) gave a 33% yield of
09d) 02.53 g) which was puri®ed by recrystallisation from
chloroform and light petroleum 040±608C) and obtained as
colourless plates, mp 221±2228C, Rf 0chloroform and ethyl-
acetate, 4:1) 0.64; IR nmax 1715, 1700 0CvO), 1595,1586
0CvC). MS m/z 3530M1), 325, 311, 310, 275, 267, 262,
261, 249, 234, 191, 57. Anal. Calcd for C22H27NO3: C,
1.2.5. 4-Acetyl-4-phenyl-1-pyrrolidinylcyclohexene *4e).
Light brown viscous mass, IR nmax: 1700 0sharp, CvO of
acetyl), 1638 0CvC).

3150
M. G. Ahmed et al. / Tetrahedron 57 42001) 3143±3150
74.78%, H, 7.64%; N, 3.96. Found: C, 74.79; H, 7.74%; N,
3.94%.
the Chemistry Department of the Kent State University,
USA who ran NMR spectra of some of our compounds.
A fellowship to S. M. I. M by the University Grants Com-
mission of Bangladesh is acknowledged. A research grant to
S. A. A by the Islamic Scienti®c Educational and Cultural
Organization 0ISESCO) is gratefully acknowledged.
1.4. Synthesis of 1-phenyl-8-methyl-4*N-pyrrolidinyl)
tricyclo[5,3,1,04.9] undecan-2,6-dione*9e)
Under the same conditions as described in general method,
the reaction of 4-acetyl-4-phenyl-1-pyrrolidinylcyclo-
hexene 04e) with crotonoyl chloride produced 1-phenyl-8-
methyl-40N-pyrrolidinyl)tricyclo [5,3,1,04.9]undecan-2,6-
dione 09e) which was isolated from the ether extract of the
hydrolytic mixture of the iminium salt and puri®ed with the
help of column chromatography; yield 1.48 g, 22%, colour-
less plates, mp 193±948C, Rf 0chloroform and light petro-
leum 040±608C), 4:1) 0.67; IR nmax:1715, 1700 0broad
CvO), 1650, 1600 0CvC). MS m/z 3370M1), 309, 295,
294, 267, 240, 223, 211, 178, 162, 123, 103, 70, 55. Anal.
Calcd for C22H27NO2: C, 78.33%, H, 8.01%; N, 4.15%.
Found: C, 78.38%; H, 8.11%; N, 4.14%.
References
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Acknowledgements
We gratefully acknowledge the services of Dr Abul Hussam
of the Department of Chemistry, George Mason University,
USA for running the low resolution mass spectra of our
samples. We are also grateful to Dr Mahinda Gangoda of
8. Cologne, J.; Vuillemet, R. Bull. Soc. Chim. 4Fr.) 1961, 2235±
2238.