Gem-disubstituted 4-oxocyclohexanes: Source for spiro heterocycles

Article abstract of DOI:10.1002/jhet.5570420508

Novel spiro heterocycles, substituted spiro-pyrimidine, pyrazole and isoxazole compounds are prepared by the cyclocondensation of 4-oxocyclohexane gem-dicarboxylates and cyano esters with nucleophiles.

Full text of DOI:10.1002/jhet.5570420508

Jul-Aug 2005
797
Gem-Disubstituted 4-Oxocyclohexanes: Source for Spiro Heterocycles
Venkatapuram Padmavathi*, Shaik Mahaboob Basha, Dandu Rangayapalle Chinna
Venkata Subbaiah, Tippireddy Venkata Ramana Reddy and Adivireddy Padmaja
Department of Chemistry, Sri Venkateswara University, Tirupati 517 502, India
Received October 28, 2004
Novel spiro heterocycles, substituted spiro-pyrimidine, pyrazole and isoxazole compounds are prepared
by the cyclocondensation of 4-oxocyclohexane gem-dicarboxylates and cyano esters with nucleophiles.
J. Heterocyclic Chem., 42, 797 (2005).
Introduction.
It is well documented that pyrimidine, thioxopyrimi-
dine, pyrazole and isoxazole derivatives were prepared
by treating gem-dicarboxylates or gem-cyanoesters with
urea, thiourea, hydrazine hydrate and hydroxylamine
hydrochloride [6]. The cyclocondensation of 2 with the
above nucleophiles afforded 7,11-diaryl-8-methyl-2,4-
diazaspiro[5.5]undecane-1,3,5,9-tetraone (5), 7,11-
diaryl-8-methyl-3-thioxo-2,4-diazaspiro[5.5]undecane-
1,5,9-trione (6), 6,10-diaryl-7-methyl-2,3-diaza-
spiro[4.5]decane-1,4,8-trione (7) and 6,10-diaryl-7-
methyl-2-oxa-3-aza-spiro[4.5]decane-1,4,8-trione (8)
(Scheme 2 and Table 1). Similar cyclocondensation of 3
with urea, thiourea, hydrazine hydrate and hydroxy-
lamine hydrochloride produced 5-amino-3-hydroxy-8-
methyl-7,11-diaryl-2,4-diazaspiro[5.5]undeca-2,4-diene-
1,9-dione (9), 5-amino-3-mercapto-8-methyl-7,11-diaryl-
2,4-diazaspiro[5.5]undeca-2,4-diene-1,9-dione (10),
4-amino-7-methyl-6,10-diaryl-2,3-diaza-spiro[4.5]dec-3-
ene-1,8-dione (11) and 4-amino-7-methyl-6,10-diaryl-2-
oxa-3-azaspiro[4.5]dec-3-ene-1,8-dione (12) (Scheme 3
and Table 1). The IR spectra of 5-12 exhibited absorption
bands in the region 1495-1515 (C=S), 1645-1720
(CONH), 1735-1775 (CO-O), 3300-3335 (OH), 3100-
In the recent past, we have been actively engaged in the
double Michael addition of active methylene compounds
to activated bis olefins [1]. The cyclic adducts obtained
have been used to prepare a variety of spiro heterocycles
[2]. In continuation of our ongoing programme to develop
some more interesting heterocycles, we thought of exploit-
ing the double Michael adducts to build spiro-heterocy-
cles; pyrimidine, pyrazole and isoxazole derivatives spiro
to cyclohexanone system.
The synthetic scheme involves passing of dry gaseous
hydrogen chloride into the mixture of unsymmetrical
ketone and benzaldehyde to get 3-methyl-4-phenyl-3-
buten-2-one [3]. The Claisen-Schmidt like reaction of the
latter with araldehyde gave 1,5-diaryl-2-methyl-1,4-penta-
dien-3-one [4] (1). The latter is subjected to double
Michael addition reaction with active methylene com-
pounds viz., dimethyl malonate, ethyl cyanoacetate and
malononitrile in alcohol with 10% sodium alkoxide as a
catalyst. The products after analysis were found to be 1,1-
dimethoxycarbonyl-3-methyl-2-phenyl-6-aryl-4-oxo-
cyclohexane (2), 1-cyano-1-ethoxycarbonyl-3-methyl-2-
phenyl-6-aryl-4-oxocyclohexane (3) and 1,1-dicyano-3-
methyl-2-phenyl-6-aryl-4-oxocyclohexane (4) [5]
(Scheme 1).
3300 (CONH and NH ). The absorption for the SH group
2
generally appears as a weak band around 2550-2600 [6],

798
V. Padmavathi, S. M. Basha, D. R. C. Venkata Subbaiah, T. V. Ramana Reddy and A. Padmaja
Vol. 42
Table 1
Physical Properties for Compounds 5-12
Comp.
M.P
(°C)
Yield
(%)
Molecular formula
(Molecular weight)
Calcd. (Found) %
H
C
N
5a
5b
296-298
208-210
228-230
298-300
294-296
212-214
225-227
290-292
182-184
200-202
222-224
226-228
176-178
218-220
224-226
230-232
292-294
218-220
238-240
289-291
280-282
222-224
236-238
282-284
215-217
234-236
240-242
244-246
185-187
180-182
190-192
198-200
56
58
55
60
59
61
57
55
65
68
62
64
67
70
64
66
57
59
56
61
62
59
68
65
67
70
72
65
70
68
59
72
C22H20N2O4
376.41
70.20
(70.32)
70.76
5.36
(5.32)
5.68
(5.63)
5.45
(5.48)
4.66
(4.70)
5.14
(5.12)
5.45
(5.40)
5.25
(5.21)
4.85
(4.90)
5.79
(5.86)
6.33
(6.28)
6.05
(6.11)
5.00
(4.92)
5.48
(5.53)
5.83
(5.80)
5.53
(5.58)
4.73
(4.70)
5.64
(5.67)
5.95
(5.90)
5.72
(5.75)
4.92
(4.90)
5.41
(5.35)
5.72
(5.76)
5.49
(5.45)
4.73
(4.75)
6.09
(6.05)
6.41
(6.37)
6.14
(6.10)
5.28
(5.24)
5.79
(5.72)
6.12
(6.15)
5.86
(5.90)
5.00
(4.97)
7.44
(7.59)
7.18
(7.08)
6.89
(6.96)
6.82
(6.76)
7.14
(7.20)
6.89
(6.98)
6.63
(6.79)
7.09
(7.02)
8.04
(8.14)
7.99
(8.07)
7.64
(7.60)
7.32
(7.40)
4.00
(4.10)
3.85
(3.80)
3.69
(3.70)
3.65
(3.60)
11.19
C23H22N2O4
390.43
(70.85)
5c
C23H22N2O5
406.43
68.00
(67.89)
64.32
(64.22)
67.33
(67.26)
67.96
(67.86)
65.38
(65.52)
66.92
(66.81)
72.39
(72.30)
71.98
(72.10)
68.84
(68.94)
65.88
(65.80)
72.19
(72.32)
72.71
(72.82)
69.64
(69.51)
65.71
(65.68)
70.38
(70.41)
70.93
(71.00)
68.13
(68.25)
64.47
(64.40)
67.49
(67.42)
68.12
(68.24)
65.54
(65.62)
62.04
(62.10)
72.60
(72.70)
73.11
(73.00)
70.00
(70.09)
66.05
(66.00)
72.39
(72.49)
72.91
(72.97)
69.76
5d
C22H19ClN2O4
410.85
6a
C22H20N2O3S
392.48
6b
C23H22N2O3S
406.50
6c
C23H22N2O4S
422.50
6d
C22H19ClN2O3S
394.85
7a
C21H20N2O3
348.40
7b
C22H22N2O3
350.41
7c
C22H22N2O4
366.41
7d
C21H19ClN2O3
382.84
8a
C21H19NO4
349.39
8b
C22H21NO4
363.42
8c
C22H21NO5
379.42
8d
C21H18ClNO4
383.83
9a
C22H21N3O3
375.43
(11.29)
10.79
(10.88)
10.36
(10.30)
10.25
(10.18)
10.73
(10.82)
10.36
(10.47)
9.97
9b
C23H23N3O3
389.45
9c
C23H23N3O4
405.45
9d
C22H20ClN3O3
409.87
10a
10b
10c
10d
11a
11b
11c
11d
12a
12b
12c
12d
C22H21N3O2S
391.50
C23H23N3O2S
405.52
C23H23N3O3S
421.52
(9.92)
9.87
C22H20ClN3O2S
425.94
(9.93)
12.09
(12.18)
11.63
(11.73)
11.13
(11.06)
11.00
(11.12)
8.04
(8.11)
7.73
(7.69)
7.40
(7.48)
7.32
(7.40)
C21H21N3O2
347.42
C22H23N3O2
361.44
C22H23N3O3
377.44
C21H20ClN3O2
381.86
C21H20N2O3
348.40
C22H22N2O3
362.42
C22H22N2O4
378.42
C21H19ClN2O3
382.84
(69.69)
65.88
(65.80)

Jul-Aug 2005
Gem-Disubstituted 4-Oxocyclohexanes: Source for Spiro Heterocycles
799
of cyclohexanone moiety whereas the pyrimidine, pyra-
zole and isoxazole rings which are nearly planar would
be perpendicular to the average plane of the cyclohexa-
none ring [7] (Figure 1).
The C -H showed a doublet at 3.85 (5a), 3.88 (6a),
7
3.79 (9a) and 3.76 (10a), C -H a quintet at 4.26 (5a),
8
4.25 (6a), 4.19 (9a) and 4.17 (10a), C -H a triplet at
10 ax
3.08 (5a), 3.07 (6a), 3.04 (9a) and 3.02 (10a), C -H
a
10 eq
double doublet at 2.64 (5a), 2.63 (6a), 2.59 (9a) and
2.61 (10a), and C -H a double doublet at 4.39 (5a),
11
1
4.38 (6a), 4.27 (9a) and 4.29 (10a) in their H NMR.
However in the compounds 7a, 8a, 11a and 12a the C -
6
H displayed a doublet at 3.96, 3.89, 3.84 and 3.87, C -H
7
a quintet at 4.33, 4.35, 4.19 and 4.21, C -H a multiplet
9
at 2.93, 2.93, 2.86 and 2.89 and C -H a double doublet
10
at 4.44, 4.41, 4.32 and 4.35. All the compounds dis-
played signals due to NH and/or NH protons, which
2
disappeared on deuteration (Table 2). The structures of
13
the compounds 5-12 were further confirmed by
C
NMR spectral data (Table 2).
EXPERIMENTAL
Melting points were determined in open capillaries on a Mel-
Temp apparatus and are uncorrected. The purity of the com-
pounds was checked by TLC (silica gel H, BDH, ethyl
acetate/hexane, 1:3). The IR spectra were recorded on a Perkin-
Elmer 1600-series FT-IR spectrophotometer using KBr pellets
-1
1
and wave numbers are given in cm . H NMR spectra were
recorded in CDCl on a Varian EM-360 spectrophotometer 300
3
13
MHz. C NMR spectra were recorded in CDCl on a Varian
3
VXR spectrometer at 75.5 MHz. All chemical shifts were
reported in ppm from TMS as an internal standard. The elemental
analyses were performed at Regional Sophisticated
Instrumentation center, Punjab University, Chandigarh, India.
1,1-Dimethoxycarbonyl-3-methyl-2-phenyl-6-aryl-4-oxocyclo-
hexane (2).
To a solution of 5 mmoles of 1 in 50 ml of methanol, 7 mmoles
of dimethyl malonate was added. Then, freshly prepared 10 ml of
10% NaOMe solution (10 ml) was added dropwise and the con-
tents were stirred for 8-10 hours at room temperature. The solu-
tion was concentrated and cooled in an ice bath. The separated
solid was collected by filtration, washed with aqueous methanol,
dried and recrystallized from methanol. 2a: yield, 70%, mp, 178-
180 °C; 2b: yield, 65%, mp, 176-177 °C; 2c: yield, 62%, mp,
190-191 °C; 2d: yield, 72%, mp, 180-181 °C.
however, this is not observed for these compounds. The
H NMR spectra of 5-12 can be rationalized by presum-
ing that the two aryl groups at C-7 and C-11 in 5, 6, 9 and
10 and at C-6 and C-10 in 7, 8, 11 and 12 are in true cis-
1,3-arrangement in the preferred rigid chair conformation
1
1-Cyano-1-ethoxycarbonyl-3-methyl-2-phenyl-6-aryl-4-oxocy-
clohexane (3).
A mixture of 5 mmoles of 1, 7 mmoles of ethyl cyanoacetate
and 40 ml of absolute ethanol were taken. To this, 10 ml of 10%
NaOEt solution was added and the reaction mixture was
refluxed for 3-4 hours. The contents were concentrated and kept
in refrigerator overnight. The separated solid was collected by
filtration, washed with cold alcohol, dried and recrystallized
from ethanol. 3a: yield, 72%, mp, 129-130 °C; 3b: yield, 70%,

800
V. Padmavathi, S. M. Basha, D. R. C. Venkata Subbaiah, T. V. Ramana Reddy and A. Padmaja
Vol. 42
Table 2
Spectroscopic Data of Compounds 5-12
1H NMR (CDCl3), ppm
13C NMR (CDCl3), ppm
Compd.
5a
0.96 (d, 3H, CH3), 2.64 (dd, 1H, C10-Heq, J=14.5, 4.6 Hz), 3.08 (t, 1H, 12.4 (CH3), 179.6 (C1 & C5), 164.5 (C3), 60.7 (C6),
C10-Hax), 3.85 (d, 1H, C7-H, J= 6.5 Hz), 4.26 (q, 1H, C8-H), 4.39 (dd, 1H, 44.6 (C7), 47.3 (C8), 205.4 (C9), 45.5 (C10), 42.8 (C11),
C11-H, J=13.8 Hz), 7.08-7.34 (m, 10H, Ar-H), 10.82 (bs, 2H, NH)
126.9, 128.7, 139.8 (Ar-C)
5b
5c
0.98 (d, 3H, CH3), 2.32 (s, 3H, Ar-CH3), 2.65 (dd, 1H, C10-Heq, J=14.4, 12.2 (CH3), 21.4 (Ar-CH3), 178.5 (C1 & C5), 166.3
4.6 Hz), 3.11 (t, 1H, C10-Hax), 3.83 (d, 1H, C7-H, J= 6.3 Hz), 4.24 (q, 1H, (C3), 59.5 (C6), 43.9 (C7), 47.7 (C8), 204.2 (C9), 44.9
C8-H), 4.32 (dd, 1H, C11-H, J=13.5 Hz), 6.98-7.36 (m, 9H, Ar-H), 10.76 (C10), 43.2 (C11), 126.2, 128.1, 128.8, 129.6, 135.4,
(bs, 2H, NH)
136.7, 140.2 (Ar-C)
0.89 (d, 3H, CH3), 2.65 (dd, 1H, C10-Heq, J=14.5, 4.5 Hz), 3.13 (t, 1H, 12.2 (CH3), 51.8 (Ar-OCH3), 179.2 (C1 & C5), 164.2
C10-Hax), 3.75 (s, 3H, Ar-OCH3), 3.91 (d, 1H, C7-H, J= 6.2 Hz), 4.28 (q, (C3), 60.2 (C6), 43.8 (C7), 47.5 (C8), 202.6 (C9), 45.2
1H, C8-H), 4.38 (dd, 1H, C11-H, J=13.6 Hz), 6.65-7.32 (m, 9H, Ar-H), (C10), 42.9 (C11), 114.3, 126.4, 129.3, 130.5, 132.2,
10.79 (bs, 2H, NH)
140.2, 160.1 (Ar-C)
5d
6a
6b
1.04 (d, 3H, CH3), 2.66 (dd, 1H, C10-Heq, J=14.3, 4.5 Hz), 3.11 (t, 1H, 12.6 (CH3), 176.5 (C1 & C5), 165.3 (C3), 60.6 (C6),
C10-Hax), 3.89 (d, 1H, C7-H, J= 6.4 Hz), 4.25 (q, 1H, C8-H), 4.38 (dd, 1H, 43.7 (C7), 48.2 (C8), 202.5 (C9), 45.6 (C10), 41.8 (C11),
C11-H, J=13.5 Hz), 7.14-7.35 (m, 9H, Ar-H), 10.87 (bs, 2H, NH)
126.5, 128.2, 128.8, 130.2, 132.0, 138.4, 140.2 (Ar-C)
0.89 (d, 3H, CH3), 2.63 (dd, 1H, C10-Heq, J=14.3, 4.5 Hz), 3.07 (t, 1H, 12.3 (CH3), 174.8 (C1 & C5), 159.6 (C3), 59.8 (C6),
C10-Hax), 3.88 (d, 1H, C7-H, J= 6.4 Hz), 4.25 (q, 1H, C8-H), 4.38 (dd, 1H, 43.5 (C7), 46.9 (C8), 203.7 (C9), 42.7 (C10), 40.5 (C11),
C11-H, J=13.6 Hz), 7.04-7.42 (m, 10H, Ar-H), 9.87 (bs, 2H, NH)
126.5, 128.9, 140.2 (Ar-C)
0.87 (d, 3H, CH3), 2.24 (s, 3H, Ar-CH3), 2.61 (dd, 1H, C10-Heq, J=14.4, 12.1 (CH3), 21.5 (Ar-CH3), 175.2 (C1 & C5), 159.3
4.7 Hz), 3.11 (t, 1H, C10-Hax), 3.85 (d, 1H, C7-H, J= 6.5 Hz), 4.27 (q, 1H, (C3), 58.7 (C6), 43.9 (C7), 47.1 (C8), 202.6 (C9), 42.3
C8-H), 4.41 (dd, 1H, C11-H, J=13.8 Hz), 6.94-7.40 (m, 9H, Ar-H), 9.85 (bs, (C10), 41.6 (C11), 126.4, 128.5, 128.9, 129.8, 135.6,
2H, NH)
137.1, 140.5 (Ar-C)
6c
0.93 (d, 3H, CH3), 2.60 (dd, 1H, C10-Heq, J=14.2, 4.5 Hz), 3.09 (t, 1H, 12.2 (CH3), 51.5 (Ar-OCH3), 177.3 (C1 & C5), 158.4
C10-Hax), 3.76 (s, 3H, Ar-OCH3), 3.85 (d, 1H, C7-H, J= 6.5 Hz), 4.26 (q, (C3), 60.1 (C6), 42.8 (C7), 46.5 (C8), 203.3 (C9), 42.9
1H, C8-H), 4.37 (dd, 1H, C11-H, J=13.5 Hz), 6.96-7.39 (m, 9H, Ar-H), 9.91 (C10), 41.2 (C11), 114.2, 126.3, 129.5, 130.0, 131.1,
(bs, 2H, NH)
132.1, 140.4, 160.3 (Ar-C)
6d
7a
7b
7c
0.95 (d, 3H, CH3), 2.66 (dd, 1H, C10-Heq, J=14.3, 4.4 Hz), 3.09 (t, 1H, 12.0 (CH3), 177.5 (C1 & C5), 158.1 (C3), 59.6 (C6),
C10-Hax), 3.89 (d, 1H, C7-H, J= 6.5 Hz), 4.23 (q, 1H, C8-H), 4.42 (dd, 1H, 43.7 (C7), 47.1 (C8), 202.7 (C9), 41.9 (C10), 40.3 (C11),
C11-H, J=13.5 Hz), 7.15-7.48 (m, 9H, Ar-H), 9.94 (bs, 2H, NH)
126.4, 128.5, 129.3, 130.4, 132.1, 138.6, 141.3 (Ar-C)
1.02 (d, 3H, CH3), 2.93 (m, 2H, C9-H), 3.96 (d, 1H, C6-H, J= 6.7 Hz), 4.33 11.9 (CH3), 170.6 (C1 & C4), 60.5 (C5), 44.7 (C6), 46.8
(q, 1H, C7-H), 4.44 (dd, 1H, C10-H, J=13.5 Hz), 7.04-7.43 (m, 10H, Ar-H), (C7), 202.3 (C8), 45.7 (C9), 43.6 (C10), 126.3, 129.6,
10.94 (bs, 2H, NH)
140.8 (Ar-C)
0.99 (d, 3H, CH3), 2.24 (s, 3H, Ar-CH3), 2.90 (m, 2H, C9-H), 3.97 (d, 1H, 11.6 (CH3), 21.4 (Ar-CH3), 171.2 (C1 & C4), 60.9 (C5),
C6-H, J= 6.5 Hz), 4.29 (q, 1H, C7-H), 4.45 (dd, 1H, C10-H, J=13.3 Hz), 43.9 (C6), 46.6 (C7), 202.5 (C8), 45.8 (C9), 43.4 (C10),
6.95-7.41 (m, 9H, Ar-H), 10.89 (bs, 2H, NH) 126.5, 128.7, 129.2 (Ar-C)
1.01 (d, 3H, CH3), 2.95 (m, 2H, C9-H), 3.78 (s, 3H, Ar-OCH3), 3.94 (d, 12.0 (CH3), 51.8 (Ar-OCH3), 170.7 (C1 & C4), 60.8
1H, C6-H, J= 6.5 Hz), 4.34 (q, 1H, C7-H), 4.42 (dd, 1H, C10-H, J=13.2 Hz), (C5), 43.8 (C6), 46.1 (C7), 202.2 (C8), 45.9 (C9), 42.9
6.97-7.44 (m, 9H, Ar-H), 10.90 (bs, 2H, NH)
(C10), 114.6, 126.4, 128.6, 129.9, 130.5, 132.6, 140.4,
160.6 (Ar-C)
7d
8a
8b
1.05 (d, 3H, CH3), 2.96 (m, 2H, C9-H), 3.95 (d, 1H, C6-H, J= 6.6 Hz), 4.35 11.9 (CH3), 171.2 (C1 & C4), 60.8 (C5), 45.1 (C6), 46.3
(q, 1H, C7-H), 4.47 (dd, 1H, C10-H, J=13.3 Hz), 7.12-7.47 (m, 9H, Ar-H), (C7), 202.7 (C8), 45.5 (C9), 43.7 (C10), 126.3, 128.8,
10.98 (bs, 2H, NH)
129.2, 131.4, 132.2, 138.6, 141.2 (Ar-C)
1.04 (d, 3H, CH3), 2.93 (m, 2H, C9-H), 3.89 (d, 1H, C6-H, J= 6.7 Hz), 4.35 11.3 (CH3), 169.4 (C1), 171.6 (C4), 60.4 (C5), 44.9 (C6),
(q, 1H, C7-H), 4.41 (dd, 1H, C10-H, J=13.4 Hz), 7.10-7.45 (m, 10H, Ar-H), 45.8 (C7), 203.3 (C8), 45.7 (C9), 43.5 (C10), 125.9,
10.87 (bs, 1H, NH) 129.7, 140.3 (Ar-C)
1.02 (d, 3H, CH3), 2.23 (s, 3H, Ar-CH3), 2.91 (m, 2H, C9-H), 3.90 (d, 1H, 11.5 (CH3), 21.6 (Ar-CH3), 168.2 (C1), 170.6 (C4), 60.6
C6-H, J= 6.6 Hz), 4.34 (q, 1H, C7-H), 4.43 (dd, 1H, C10-H, J=13.5 Hz), (C5), 44.8 (C6), 46.1 (C7), 202.6 (C8), 45.3 (C9), 43.6
6.97-7.43 (m, 9H, Ar-H), 10.92 (bs, 1H, NH)
(C10), 126.2, 128.1, 128.8, 129.7, 135.2, 137.4, 140.7
(Ar-C)
8c
1.04 (d, 3H, CH3), 2.94 (m, 2H, C9-H), 3.76 (s, 3H, Ar-OCH3), 3.87 (d, 11.8 (CH3), 51.3 (Ar-OCH3), 169.5 (C1), 171.6 (C4),
1H, C6-H, J= 6.6 Hz), 4.33 (q, 1H, C7-H), 4.42 (dd, 1H, C10-H, J=13.3 Hz), 60.5 (C5), 45.2 (C6), 45.8 (C7), 201.8 (C8), 45.6 (C9),
6.95-7.43 (m, 9H, Ar-H), 10.93 (bs, 1H, NH)
43.3 (C10), 115.1, 126.8, 129.9, 131.2, 132.4, 140.3,
160.5 (Ar-C)
8d
9a
9b
1.06 (d, 3H, CH3), 2.95 (m, 2H, C9-H), 3.88 (d, 1H, C6-H, J= 6.6 Hz), 4.36 12.2 (CH3), 169.9 (C1), 172.3 (C4), 61.2 (C5), 44.9 (C6),
(q, 1H, C7-H), 4.45 (dd, 1H, C10-H, J=13.6 Hz), 7.14-7.46 (m, 9H, Ar-H), 46.3 (C7), 201.9 (C8), 45.9 (C9), 44.1 (C10), 126.2,
10.92 (bs, 1H, NH)
129.2, 129.8, 130.7, 132.5, 138.7, 141.2 (Ar-C)
0.87 (d, 3H, CH3), 2.59 (dd, 1H, C10-Heq, J=14.3, 4.5 Hz), 3.04 (t, 1H, 12.2 (CH3), 177.4 (C1), 162.6 (C3), 187.3 (C5), 61.2
C10-Hax), 3.79 (d, 1H, C7-H, J= 6.6 Hz), 4.19 (q, 1H, C8-H), 4.27 (dd, 1H, (C6), 45.4 (C7), 48.3 (C8), 202.9 (C9), 45.8 (C10), 43.7
C11-H, J=13.6 Hz), 6.69 (bs, 3H, NH2 & OH), 7.02-7.44 (m, 10H, Ar-H)
(C11), 126.4, 129.7, 141.6 (Ar-C)
0.89 (d, 3H, CH3), 2.24 (s, 3H, Ar-CH3), 2.58 (dd, 1H, C10-Heq, J=14.2, 12.1 (CH3), 21.2 (Ar-CH3), 176.7 (C1), 161.5 (C3),
4.4 Hz), 3.06 (t, 1H, C10-Hax), 3.77 (d, 1H, C7-H, J= 6.5 Hz), 4.18 (q, 1H, 188.2 (C5), 60.9 (C6), 45.2 (C7), 47.6 (C8), 202.8 (C9),
C8-H), 4.24 (dd, 1H, C11-H, J=13.3 Hz), 6.67 (bs, 3H, NH2 & OH), 6.93- 45.5 (C10), 43.2 (C11), 126.6, 128.8, 129.2, 129.8,
7.46 (m, 9H, Ar-H)
135.6, 137.2, 146.2 (Ar-C)

Jul-Aug 2005
Gem-Disubstituted 4-Oxocyclohexanes: Source for Spiro Heterocycles
801
Table 2 (continued)
Compd.
1H NMR (CDCl3), ppm
13C NMR (CDCl3), ppm
9c
0.86 (d, 3H, CH3), 2.63 (dd, 1H, C10-Heq, J=14.4, 4.6 Hz), 3.07 (t, 1H, 12.2 (CH3), 51.2 (Ar-OCH3), 175.7 (C1), 161.6 (C3),
C10-Hax), 3.74 (s, 3H, Ar-OCH3), 3.78 (d, 1H, C7-H, J= 6.5 Hz), 4.21 (q, 189.2 (C5), 60.5 (C6), 45.3 (C7), 47.2 (C8), 202.2 (C9),
1H, C8-H), 4.26 (dd, 1H, C11-H, J=13.5 Hz), 6.71 (bs, 3H, NH2 & OH), 45.5 (C10), 43.6 (C11), 115.4, 127.2, 130.1, 131.5,
6.96-7.48 (m, 9H, Ar-H)
132.8, 141.6, 160.7 (Ar-C)
9d
0.91 (d, 3H, CH3), 2.62 (dd, 1H, C10-Heq, J=14.4, 4.5 Hz), 3.07 (t, 1H, 12.0 (CH3), 176.9 (C1), 162.7 (C3), 189.4 (C5), 60.8
C10-Hax), 3.78 (d, 1H, C7-H, J= 6.5 Hz), 4.21 (q, 1H, C8-H), 4.32 (dd, 1H, (C6), 45.6 (C7), 48.0 (C8), 202.3 (C9), 45.6 (C10), 43.3
C11-H, J=13.5 Hz), 6.71 (bs, 3H, NH2 & OH), 7.14-7.48 (m, 9H, Ar-H)
(C11), 126.3, 129.2, 130.2, 131.2, 132.5, 138.8, 141.5
(Ar-C)
10a
10b
0.91 (d, 3H, CH3), 2.61 (dd, 1H, C10-Heq, J=14.4, 4.7 Hz), 3.02 (t, 1H, 12.0 (CH3), 176.7 (C1), 162.9 (C3), 179.9 (C5), 60.2
C10-Hax), 3.76 (d, 1H, C7-H, J= 6.4 Hz), 4.17 (q, 1H, C8-H), 4.29 (dd, 1H, (C6), 46.1 (C7), 47.9 (C8), 201.4 (C9), 44.6 (C10), 42.8
C11-H, J=13.4 Hz), 6.58 (bs, 3H, NH2 & SH), 7.00-7.48 (m, 10H, Ar-H)
(C11), 126.4, 129.6, 141.6 (Ar-C)
0.87 (d, 3H, CH3), 2.23 (s, 3H, Ar-CH3), 2.62 (dd, 1H, C10-Heq, J=14.3, 12.1 (CH3), 21.8 (Ar-CH3), 176.6 (C1), 162.9 (C3),
4.5 Hz), 3.04 (t, 1H, C10-Hax), 3.79 (d, 1H, C7-H, J= 6.5 Hz), 4.14 (q, 1H, 178.7 (C5), 60.3 (C6), 45.9 (C7), 47.6 (C8), 202.2 (C9),
C8-H), 4.32 (dd, 1H, C11-H, J=13.2 Hz), 6.62 (bs, 3H, NH2 & SH), 6.92- 43.6 (C10), 43.3 (C11), 126.7, 128.6, 129.3, 130.2,
7.45 (m, 9H, Ar-H)
135.4, 136.3, 141.5 (Ar-C)
10c
10d
0.88 (d, 3H, CH3), 2.64 (dd, 1H, C10-Heq, J=14.5, 4.8 Hz), 3.02 (t, 1H, 12.8 (CH3), 51.5 (Ar-OCH3), 175.8 (C1), 161.3 (C3),
C10-Hax), 3.74 (d, 1H, C7-H, J= 6.3 Hz), 3.79 (s, 3H, Ar-OCH3), 4.18 (q, 179.2 (C5), 60.5 (C6), 46.0 (C7), 47.8 (C8), 202.6 (C9),
1H, C8-H), 4.28 (dd, 1H, C11-H, J=13.5 Hz), 6.61 (bs, 3H, NH2 & SH), 44.5 (C10), 42.6 (C11), 115.2, 126.8, 129.5, 130.7,
6.91-7.47 (m, 9H, Ar-H)
132.4, 140.5, 160.3 (Ar-C)
0.92 (d, 3H, CH3), 2.68 (dd, 1H, C10-Heq, J=14.3, 4.8 Hz), 3.05 (t, 1H, 12.5 (CH3), 177.2 (C1), 161.4 (C3), 179.0 (C5), 60.2
C10-Hax), 3.79 (d, 1H, C7-H, J= 6.5 Hz), 4.19 (q, 1H, C8-H), 4.32 (dd, 1H, (C6), 45.8 (C7), 47.3 (C8), 201.6 (C9), 43.7 (C10), 41.6
C11-H, J=13.5 Hz), 6.56 (bs, 3H, NH2 & SH), 7.12-7.50 (m, 9H, Ar-H)
(C11), 126.9, 128.7, 129.2, 130.5, 132.2, 138.6, 141.4
(Ar-C)
11a
11b
1.01 (d, 3H, CH3), 2.86 (m, 2H, C9-H), 3.84 (d, 1H, C6-H, J= 6.5 Hz), 4.19 11.9 (CH3), 173.2 (C1), 165.5 (C4), 60.8 (C5), 45.3 (C6),
(q, 1H, C7-H), 4.32 (dd, 1H, C10-H, J=13.3 Hz), 6.61 (bs, 3H, NH2 & NH), 47.7 (C7), 200.8 (C8), 44.9 (C9), 43.7 (C10), 126.3,
6.99-7.39 (m, 10H, Ar-H)
1.03 (d, 3H, CH3), 2.20 (s, 3H, Ar-CH3), 2.84 (m, 2H, C9-H), 3.85 (d, 1H, 11.7 (CH3), 21.5 (Ar-CH3), 173.6 (C1), 166.7 (C4), 60.7
128.9, 140.9 (Ar-C)
C6-H, J= 6.4 Hz), 4.21 (q, 1H, C7-H), 4.29 (dd, 1H, C10-H, J=13.5 Hz), (C5), 44.9 (C6), 47.5 (C7), 201.2 (C8), 44.6 (C9), 42.9
6.58 (bs, 3H, NH2 & NH), 6.87-7.36 (m, 9H, Ar-H)
(C10), 126.9, 128.7, 129.5, 130.4, 135.6, 136.7, 141.2
(Ar-C)
0.99 (d, 3H, CH3), 2.88 (m, 2H, C9-H), 3.75 (s, 3H, Ar-OCH3), 3.88 (d, 11.3 (CH3), 51.6 (Ar-OCH3), 172.9 (C1), 165.6 (C4),
11c
1H, C6-H, J= 6.2 Hz), 4.16 (q, 1H, C7-H), 4.35 (dd, 1H, C10-H, J=13.2 Hz), 60.8 (C5), 45.2 (C6), 47.4 (C7), 201.5 (C8), 44.8 (C9),
6.59 (bs, 3H, NH2 & NH), 6.94-7.38 (m, 9H, Ar-H)
43.5 (C10), 114.8, 126.5, 129.7, 130.3, 132.6, 140.4,
160.5 (Ar-C)
11d
12a
12b
1.02 (d, 3H, CH3), 2.86 (m, 2H, C9-H), 3.87 (d, 1H, C6-H, J= 6.6 Hz), 4.18 11.5 (CH3), 171.8 (C1), 166.9 (C4), 60.9 (C5), 45.4 (C6),
(q, 1H, C7-H), 4.36 (dd, 1H, C10-H, J=13.3 Hz), 6.65 (bs, 3H, NH2 & NH), 47.8 (C7), 200.3 (C8), 44.9 (C9), 43.9 (C10), 126.7,
7.12-7.48 (m, 9H, Ar-H)
128.5, 129.6, 130.4, 132.6, 138.8, 141.3 (Ar-C)
1.06 (d, 3H, CH3), 2.89 (m, 2H, C9-H), 3.87 (d, 1H, C6-H, J= 6.6 Hz), 4.21 12.2 (CH3), 170.4 (C1), 164.1 (C4), 60.7 (C5), 45.5 (C6),
(q, 1H, C7-H), 4.35 (dd, 1H, C10-H, J=13.2 Hz), 6.59 (bs, 2H, NH2), 6.95- 47.9 (C7), 201.6 (C8), 45.1 (C9), 43.8 (C10), 126.9,
7.42 (m, 10H, Ar-H)
1.03 (d, 3H, CH3), 2.21 (s, 3H, Ar-CH3), 2.87 (m, 2H, C9-H), 3.84 (d, 1H, 12.1 (CH3), 21.2 (Ar-CH3), 170.8 (C1), 165.2 (C4), 61.2
129.8, 141.3 (Ar-C)
C6-H, J= 6.5 Hz), 4.22 (q, 1H, C7-H), 4.38 (dd, 1H, C10-H, J=13.3 Hz), (C5), 44.8 (C6), 48.2 (C7), 201.7 (C8), 44.3 (C9), 43.6
6.57 (bs, 2H, NH2), 6.88-7.43 (m, 9H, Ar-H)
(C10), 126.7, 128.5, 129.4, 130.3, 135.2, 136.6, 140.9
(Ar-C)
1.04 (d, 3H, CH3), 2.90 (m, 2H, C9-H), 3.78 (s, 3H, Ar-OCH3), 3.90 (d, 11.9 (CH3), 51.7 (Ar-OCH3), 171.9 (C1), 164.9 (C4),
12c
12d
1H, C6-H, J= 6.5 Hz), 4.23 (q, 1H, C7-H), 4.38 (dd, 1H, C10-H, J=13.3 Hz), 61.3 (C5), 44.9 (C6), 48.3 (C7), 200.9 (C8), 43.9 (C9),
6.62 (bs, 2H, NH2), 6.88-7.45 (m, 9H, Ar-H)
42.8 (C10), 115.3, 126.7, 129.4, 130.3, 132.8, 140.6,
160.5 (Ar-C)
1.06 (d, 3H, CH3), 2.92 (m, 2H, C9-H), 3.92 (d, 1H, C6-H, J= 6.5 Hz), 4.24 12.4 (CH3), 171.3 (C1), 163.8 (C4), 61.8 (C5), 45.7 (C6),
(q, 1H, C7-H), 4.36 (dd, 1H, C10-H, J=13.3 Hz), 6.64 (bs, 2H, NH2), 7.15- 48.5 (C7), 202.6 (C8), 44.7 (C9), 43.6 (C10), 126.8,
7.48 (m, 9H, Ar-H)
128.6, 129.5, 130.3, 132.5, 138.7, 141.1 (Ar-C)
mp, 131-132 °C; 3c: yield, 75%, mp, 125-126 °C; 3d: yield,
68%, mp, 148-149 °C.
7,11-Diaryl-8-methyl-2,4-diaza-spiro[5.5]undecane-1,3,5,9-
tetraone (5) 7,11-Diaryl-8-methyl-3-thioxo-2,4-diaza-spiro[5.5]-
undecane-1,5,9-trione (6) 6,10-Diaryl-7-methyl-2,3-diaza-spiro-
[4.5]decane-1,4,8-trione (7) and 6,10-Diaryl-7-methyl-2-oxa-3-
azaspiro[4.5]decane-1,4,8-trione (8).
1,1-Dicyano-3-methyl-2-phenyl-6-aryl-4-oxocyclohexane (4).
A solution of 5 mmoles of 1 and 7 mmoles of malononitrile in
50 ml methanol was stirred for 30 minutes and then Triton-B (8 ml)
was added. The stirring was continued for 5-6 hours at room tem-
perature. The separated solid was collected by filtration, washed
with cold aqueous methanol, dried and recrystallized from alcohol.
4a: yield, 74%, mp, 154-155 °C; 4b: yield, 68%, mp, 136-138 °C;
4c: yield, 70%, mp, 144-146 °C; 4d: yield, 65%, mp, 138-140 °C.
A mixture of 5 mmoles of 2 and urea or thiourea (5 mmoles) or
80% hydrazine hydrate (8 mmoles) or hydroxylamine hydrochlo-
ride (5 mmoles) in 15 ml of ethanol and 5 ml of 10% NaOMe was
refluxed for 8-10 hours. Then, it was cooled and poured onto
crushed ice containing concentrated HCl. The product obtained

802
V. Padmavathi, S. M. Basha, D. R. C. Venkata Subbaiah, T. V. Ramana Reddy and A. Padmaja
Vol. 42
[2a] D. Bhaskar Reddy, V. Padmavathi, B. Seenaiah and M. V.
Ramana Reddy, Org. Prep. Proced. Int., 24, 21 (1992); [b] D. Bhaskar
Reddy, V. Padmavathi and P. V. Ramana Reddy, Indian J. Chem., 31B,
774 (1992); [c] D. Bhaskar Reddy, V. Padmavathi, B. Seenaiah and A.
Padmaja, Heteroatom Chem., 4, 55 (1993); [d] D. Bhaskar Reddy, M. V.
Ramana Reddy and V. Padmavathi, Indian J. Chem., 37B, 167 (1998);
[e] D. Bhaskar Reddy, M. V. Ramana Reddy and V. Padmavathi,
Heteroatom Chem., 10, 17 (1999); [f] D. Bhaskar Reddy, N.
Chandrasekhar Babu and V. Padmavathi, Heteroatom Chem., 12, 131
(2001).
[3] M. T. Bogert and D. Davidson, J. Am. Chem. Soc., 54, 334
(1932).
[4] K. Ramalingam, K. D. Berlin, R. A. Loghry, D. H. Helm and
N. Satya Murthy, J. Org. Chem., 44, 477 (1979).
[5] V. Padmavathi, T. V. Ramana Reddy, K. Venugopal Reddy,
K. Audisesha Reddy and D. Bhaskar Reddy, Indian J. Chem., 40B, 667
(2001).
was collected by filtration, dried and purified by recrystallization
from methanol.
5-Amino-3-hydroxy-8-methyl-7,11-diaryl-2,4-diaza-spiro-
[5.5]undeca-2,4-diene-1,9-dione (9) 5-Amino-3-mercapto-8-
methyl-7,11-diaryl-2,4-diaza-spiro[5.5]undeca-2,4-diene-1,9-
dione (10) 4-Amino-7-methyl-6,10-diaryl-2,3-diaza-spiro[4.5]-
dec-3-ene-1,8-dione (11) and 4-Amino-7-methyl-6,10-diaryl-2-
oxa-3-aza-spiro[4.5]dec-3-ene-1,8-dione (12).
To a solution of 5 mmoles of 3 in 15 ml of ethanol, urea or
thiourea (5 mmoles) or 80% hydrazine hydrate (8 mmoles) or
hydroxylamine hydrochloride (5 mmoles) and 5 ml of 10%
NaOEt was added and refluxed for 8-12 hours. The contents were
cooled and poured onto crushed ice containing concentrated HCl.
The product that separated was collected by filtration and dried.
Recrystallization of the crude compound from ethanol resulted
pure sample.
[6a] V. G. Voronin, O. Yu. Polevaya, V. G. Makhanova, M. A.
Landau, V. M. Kolbanov, T. P. Privol'neva, V. V. Chugunov and E. F.
Laverlskaya, Khim-Farm Zh., 10, 43 (1976); [b] M. I. Al-Asmawi, K.
M. Ghoneim and M. Khalifa, Pharmazie, 35, 591 (1980); [c] C.
Abdehmajid and F. Houda, Ann Furin Fr., 38, 429 (1980); [d] D.
Bhaskar Reddy, N. Chandrasekhar Babu and V. Padmavathi, J.
Heterocyclic Chem., 38, 769 (2001); [e] V. Padmavathi, A. Balaiah, K.
Venugopal Reddy, A. Padmaja and D. Bhaskar Reddy, Indian J. Chem.,
41B, 1670 (2002); [f] V. Padmavathi, A. Balaiah, A. Padmaja and D.
Bhaskar Reddy, Phosphorous, Sulfur & Silicon, 177, 2791 (2002); [g] V.
Padmavathi, A. Balaiah and D. Bhaskar Reddy, J. Heterocyclic Chem.,
39, 649 (2002); [h] V. Padmavathi, A. Balaiah, T. V. Ramana Reddy, B.
Jagan Mohan Reddy and D. Bhaskar Reddy, Heteroatom Chem., 14, 513
(2003); [i] V. Padmavathi, D. R. C. Venkata Subbaiah, M. Rajagopala
Sarma and A. Balaiah, Heteroatom Chem., 15, 477 (2003).
[7] R. M. Silverstein, G. C. Bassler and T. C. Morrill,
Spectrometric Identification of Organic Compounds fifth edition, John
Wiley & Sons, New York.
Acknowledgements.
We thank Prof. D. Bhaskar Reddy, Emeritus Professor of UGC
for his helpful discussion and suggestion. The authors are grate-
ful to CSIR, New Delhi for financial assistance under major
research project.
REFERENCES AND NOTES
*
To whom correspondence should be addressed: Email: vkpu-
ram2001@yahoo.com
[1a] D. Bhaskar Reddy, V. Padmavathi and S. Reddy, Sulfur Lett.,
13, 123 (1991); [b] D. Bhaskar Reddy, V. Padmavathi and M. Muralidhar
Reddy, Indian J. Chem., 31B, 407 (1992); [c] V. Padmavathi, T. V.
Ramana Reddy, K. Venugopal Reddy, K. Audisesha Reddy and D.
Bhaskar Reddy, Indian J. Chem., 40B, 667 (2001); [d] D. Bhaskar Reddy,
N. Chandrasekhar Babu and V.Padmavathi, J. Heterocyclic Chem., 38,
769 (2001).
[8] H. A. P. De Jongh and H. Blynberg, Tetrahedron, 21, 515
(1965).