Synthesis of a series of highly substituted cyclohexanols via Michael addition in an aqueous medium

Article abstract of DOI:10.3184/174751911X12977065405044

The Michael addition of active methylene compounds or nitromethane to chalcones in an aqueous medium and catalysed by tetrabutyl ammonium hydroxide (TBAOH) to afford highly substituted cyclohexanols is described. The protocol provides an efficient route f

Full text of DOI:10.3184/174751911X12977065405044

JOURNAL OF CHEMICAL RESEARCH 2011
RESEARCH PAPER 147
MARCH, 147–150
Synthesis of a series of highly substituted cyclohexanols via Michael
addition in an aqueous medium
Guo-ping Lu and Chun Cai*
College of Chemical Engineering, Nanjing University of Science &Technology, Nanjing 210094, P. R. China
The Michael addition of active methylene compounds or nitromethane to chalcones in an aqueous medium and
catalysed by tetrabutyl ammonium hydroxide (TBAOH) to afford highly substituted cyclohexanols is described. The
protocol provides an efficient route for the synthesis of highly substituted cyclohexanols, with short reaction time,
and a range of different substrates in the absence of toxic organic solvents.
Keywords: Michael addition, tetrabutyl ammonium hydroxide, highly substituted cyclohexanol, aqueous medium
The Michael addition is an important, highly atom-economical
reaction for the formation of C–C bonds, affording complex
molecules such as tri-carbonylcompounds,1,2 nitrogen-con-
taining ketoesters,3,4 various heterocycle compounds,5–8 and
alkylated dicarbonyls.9,10 Many of these products are important
organic intermediates in synthetic organic chemistry.
Table 1 Optimisation the reaction conditionsa
The use of water in organic reactions offers significant envi-
ronment advantages and has attracted a great deal of interest in
recent years, because water is considered as a cheap, safe and
‘green’ solvent.11–13 Nevertheless, the organic transformations
that can be carried out in water are limited, owing to the
poor solubility of organic reactants in water. In many cases,
phase-transfer catalysts (PTC)14–16 or organic co-solvents17,18
are added to increase the reaction rate by improving the
solubility of reactants in water.
As a part of our interest in reactions in aqueous medium, we
have explored the Michael addition reactions of malononitrile
to chalcones in aqueous medium. This has led to an efficient
synthesis of a series of highly substituted cyclohexanols.
Initially, the reaction of chalcone and malononitrile was per-
formed in water using piperidine as catalyst at 80°C for 6h. A
white solid was obtained, which was identified as a highly sub-
stituted cyclohexanol 3a on the basis of its spectroscopic and
analytical data. Previously, the synthesis of highly substituted
cyclohexanols has been reported from chalcones and malono-
nitrile or nitromethane.19–23 However, the harsh conditions or
long reaction times were required, and the scope of these pro-
tocols was limited. Consequently, we sought a more efficient
procedure for a wider range of different substrates.
Entry Time
Base(10mol%) Additive(0.1g)
Yield/%b
1
2
3
4
5
6
7
8
6h
piperidine
DABCOc
Et3N
—
—
45
10
2h
2h
—
66
2h
Bu3N
—
—
TBAB
—
—
70
2h
NaOH
Bu3N
—
TBAOH
24
15min
15min
15min
80
NRd
86
a Reaction condition: 1a 1mmol, 2a 0.5mmol, H2O 5mL, 80°C.
b Isolated yield of product.
c DABCO is 1,4-diazabicyclo[2.2.2]octane.
d No reaction.
Table 2 The synthesis of
a series of highly substituted
cyclohexanols via Micheal addition in aqueous mediuma
The reaction of chalcone and malononitrile was selected as
a model reaction to optimise the reaction conditions. A series
of bases including piperidine, DABCO, NEt3, NBu3, NaOH,
were screened (Table 1, entries 1–5). To improve the unsatis-
factory results, tetrabutyl ammonium bromide (TBAB) as a
phase-transfer catalyst (PTC) was added, and a good yield of
80% was obtained at 15min (Table 1, entry 6). No reaction
occurred when the reaction was carried out in water without
base (Table 1, entry 7). The above results suggested that the
base was necessary in the reaction, and PTC could increase the
reaction rate. Thus we decided to use tetrabutyl ammonium
hydroxide (TBAOH) as catalyst, which played the role of both
base and PTC in the reaction. The yield was also satisfactory
(Table 1, entry 8).
With the optimised conditions in placed, various chalcones
were used to reveal the generality and scope of the new proto-
col (Table 2, entries 1–6). The results indicated that chalcones
containing electron-drawing groups or electron-donating
groups could react well with malononitrile to give the desired
product 3a–e in good or moderate yields. Instead of malononi-
trile, ethyl cyanoacetate also gave a satisfactory yield of the
desired product 3g (Table 2, entry 7).
Entry Time/h R1
R2
2
Product Yield/%b
1
2
0.25
0.25
0.25
0.25
0.5
0.5
0.5
3
H
H
2a
2a
2a
2a
2a
3a
3b
3c
3d
3e
3f
86
4-O2N
4-Cl
4-MeO
H
H
83
3
H
81
4
H
84
5
3-Cl
71
6
H
4-MeO 2a
68
7
H
H
2b
2c
2c
2c
2c
3g
3h
3i
87
8c
9c
10c
11c
H
H
72(37)d
53
6
4-NO2
4-Cl
H
H
6
6
H
3j
71
4-Cl
3k
55
a Reaction condition: 1 1mmol, 2 0.5mmol, H2O or EtOH/H2O
(v/v=1:1) 5mL, TBAOH 0.05mmol, 80°C.
b Isolated yield of product.
c The solvent is EtOH/H2O(v/v=1:1).
d The solvent is H2O.
* Correspondent. E-mail: c.cai@mail.njust.edu.cn

148 JOURNAL OF CHEMICAL RESEARCH 2011
In an effort to expand the scope of the protocol, a test
reaction of nitromethane and chalcone was performed under
similar conditions, and a low yield (37%) of the desired prod-
uct 3h was obtained. In order to improve the reaction yield,
EtOH/H2O (v/v=1:1) was employed as a solvent. The yield of
3h increased to 72%, due to the better solubility of the reac-
tants and their more efficient mixing (Table 2, entry 8). Further
investigation indicated that the reaction proceeded smoothly
when chalcones with electron-withdrawing groups were
employed (Table 2, entries 9–11). However, chalcones with
electron-donating groups such as methoxyl group only gave a
complex mixture.
meanwhile, the chemical shift of Hg is 5.18, so C–Hg is the
equatorial bond.22 The stereostructures of 3a, 3h are shown in
Scheme 2.
In conclusion, we have demonstrated a novel method for the
synthesis of highly substituted cyclohexanols by the Michael
addition of active methylene compounds or nitromethane to
chalcones. Several advantages of the protocol including shorter
reaction time, better tolerance to different substrates, and a
simple work-up procedure make it an efficient tool for the
synthesis of highly substituted cyclohexanols.
Experimental
As a consequence of these results, we also wanted to apply
the protocol for more complex active methylene compounds.
Therefore, 3-cyanoacetylindole which is an important interme-
diate for the synthesis of natural products and pharmaceuti-
cals,24,25 was used as active methylene compounds to react with
chalcone (Scheme 1). None of the desired highly substituted
cyclohexanols was obtained due to the large steric hindrance
effect between chalcone and 3-cyanoacetylindole. Compound
3l was obtaineded via Michael addition of chalcone with
3-cyanoacetyindole.
All chalcones and 3-cyanoacetylindole were prepared according to
literature methods.24,26 All other reagents were obtained from com-
mercial suppliers and used without further purification. 1H, 13C NMR
and HSQC spectra were recorded at 500MHz and 125MHz respec-
tively, in CDCl3 or DMSO-d6, and chemical shifts were reported in
ppm from internal TMS (δ). All melting points are determined uncor-
rected. ElementalanalyseswereperformedonaYanagimotoMT3CHN
recorder.
Synthesis of highly substituted cyclohexanols in aqueous medium;
general procedure
The stereostructure of the highly substituted cyclohexanols
A mixture of chalcone 1 (1mmol) and malononitrile 2 (0.5 mmol) in
H2O (5 ml) was stirred in 80°C for 5 min. Then, TBAOH (0.05 mmol,
as a 10wt.% aqueous solution) was added dropwise, and the mixture
was stirred at the same temperature for the period of time listed in
Table 2, and then cooled to room temperature. The solid precipitate
was collected, washed with water, dried and recrystallised by ethanol
to afford the desired product 3.
was established from the 1H NMR, 13C NMR and HSQC data.
1
As a representative example, the H NMR spectrum of 3a
shows a doublet at 5.24 for Ha, which the HSQC spectrum
showed was not attached to a carbon. This hydrogen forms an
intramolecular hydrogen bond with the oxygen of the carbonyl
group. The doublet is due to long range coupling with Hc
(Jac = 2.5Hz) with a rigid W geometry. The long range W
coupling also indicates the presence of a nearly perfect chair
configuration. The –(C)CHCH2– is an AMX system, and
δ = 2.31, 2.97, 4.23 corresponding to Hb, Hc, Hd respectively
(Jbc = 15.0Hz, Jbd = 3.0Hz, Jcd = 13.8Hz). The –(C)CHCH(C)–
is an AB system, δ = 4.24, 4.87 assigned to He, Hf respectively
(Jef = 12.0Hz). These coupling constants correspond to the
geometry in 3a. The 13C NMR data of 3a shows a signal
at δ = 204.08 characteristic of an aroyl carbonyl carbon, and
there are another two signals at δ = 113.68, 113.75 due to
the cyano groups. The stereostructure of 3h is similar to 3a,
3-Benzoyl-4-hydroxy-2,4,6-triphenylcyclohexane-1,1-dicarboni-
1
trile 3a: White solid, m.p. 234–236°C (lit.21: 236–238°C). H NMR
(500MHz CDCl3) δ = 2.29–2.33 (dd, 1H, Hb, J1 = 15.0Hz, J2 = 3.0Hz),
2.94–3.00 (dt, 1H, Hc, J1 = 13.8Hz, J2 = 2.5Hz), 4.22–4.25 (dd, 1H,
Hd, J1 = 12.0Hz, J2 = 3.0Hz), 4.24 (d, 1H, He, J = 12.0Hz), 4.87 (d,
1H, Hf, J = 12.0Hz), 5.24 (d, 1H, Ha, J = 2.5Hz), 7.11–7.61 (m, 20H,
aromatic). 13C NMR (500MHz CDCl3) δ = 40.69, 46.15, 48.00, 50.28,
51.59, 74.57, 113.68 (CN), 113.75 (CN), 124.63, 127.82, 128.06,
128.12, 128.59, 128.68, 128.86, 128.94, 129.13, 129.25, 133.58,
133.67, 136.38, 137.25, 143.84, 204.08 (C=O). Anal. Calcd for
C33H26N2O2: C, 82.13; H, 5.43; N, 5.81. Found: C, 82.23; H, 5.31;
N, 5.76%.
Scheme 1
Scheme 2

JOURNAL OF CHEMICAL RESEARCH 2011 149
3-Benzoyl-4-hydroxy-2,6-bis(4-nitrophenyl)-4-phenylcyclohexane-
1,1-dicarbonitrile 3b: Light yellow solid, m.p. 216–218°C (lit.21:
217–219°C). 1H NMR (500MHz, CDCl3) δ = 2.34–2.38 (dd, 1H,
Hb, J1 = 14.5Hz, J2 = 3.0Hz), 2.96–3.02 (dt, 1H, Hc, J1 = 13.5Hz,
J2 = 2.5Hz), 4.39–4.15 (dd, 1H, Hd, J1 = 11.5Hz, J2 = 3.0Hz), 4.44 (d,
1H, He, J = 12.5Hz), 4.88 (d, 1H, Hf, J = 12.0Hz), 5.08 (d, 1H, Ha,
J = 2.0Hz), 7.14–7.17 (m, 1H, aromatic), 7.20–7.23 (m, 2H, aro-
matic), 7.27–7.30 (m, 2H, aromatic), 7.40–7.44 (m, 3H, aromatic),
7.54 (d, 2H, aromatic, J = 7.5Hz), 7.67 (d, 2H, aromatic, J = 9.0Hz),
7.79 (d, 2H, aromatic, J = 9.0Hz), 8.04 (d, 2H, aromatic, J = 9.0Hz),
8.34 (d, 2H, aromatic, J = 8.5Hz). 13C NMR (500MHz CDCl3)
δ = 40.18, 45.68, 46.69, 49.69, 51.05, 74.36, 112.79 (CN), 112.83
(CN), 123.95, 124.45, 128.10, 128.33, 128.55, 128.84, 130.01, 134.56,
136.54, 140.18, 142.63, 142.65, 148.38, 148.56, 202.68 (C=O). Anal.
Calcd for C33H24N4O6: C, 69.22; H, 4.22; N, 9.79. Found: C, 69.23;
H, 4.31; N, 9.66%.
CDCl3) δ = 0.72–0.75 (m, 3H, –CH3), 2.22–2.26 (dd, 1H, Hb, J1 =
14.5Hz, J2 = 3.0Hz), 2.97–3.02 (dt, 1H, Hc, J1 = 13.0Hz, J2 = 3.0Hz),
3.73–3.79 (m, 2H, –CH2–), 4.32–4.35 (dd, 1H, He, J1 = 12.0Hz,
J2 = 3.0Hz), 4.94 (d, 1H, Hf, J = 12.5Hz), 5.36 (d, 1H, Ha, J = 2.0Hz),
7.02–7.04 (m, 3H, aromatic), 7.09–7.14 (m, 3H, aromatic), 7.23–7.37
(m, 11H, aromatic), 7.49 (d, 2H, aromatic, J = 7.5Hz), 7.62 (d, 2H,
aromatic, J = 7.5Hz). 13C NMR (500MHz CDCl3) δ = 13.45, 41.71,
45.23, 49.34, 52.45, 59.78, 62.26, 74.99, 117.77 (CN), 124.79, 127.97,
127.98, 128.17, 128.19, 128.27, 128.41, 128.58, 133.29, 134.67,
137.94, 144.77, 166.47 (C=O), 205.37 (C=O). Anal. Calcd for
C35H31NO4: C, 79.37; H, 5.90; N, 2.64. Found: C, 79.12; H, 6.01;
N, 2.78%.
(2-Hydroxy-5-nitro-2,4,6-triphenylcyclohexyl)(phenyl)methanone
3h: White solid, m.p. 234–236°C (lit.22). 1H NMR (500MHz, CDCl3)
δ = 2.14–2.17 (dd, 1H, Hb, J1 = 13.8Hz, J2 = 3.5Hz), 3.36–3.41 (t, 1H,
Hc, J = 12.5Hz), 4.19–4.23 (m, 2H, Hd, He), 5.11 (d, 1H, Ha J = 1.0Hz),
5.17–5.19 (t, 1H, Hg, J = 4.0Hz), 5.50 (d, 1H, Hf, J = 12.0Hz), 7.05–
7.13 (m, 3H, aromatic), 7.14–7.19 (m, 5H, aromatic), 7.26–7.37 (m,
8H, aromatic), 7.45 (d, 2H, aromatic, J = 7.5Hz), 7.67 (d, 2H,
aromatic, J = 7.5Hz). 13C NMR (500MHz CDCl3) δ = 37.15, 41.33,
46.54, 48.73, 75.32, 93.57, 124.89, 127.33, 127.35, 127.88, 127.97,
128.14, 128.18, 128.36, 128.74, 128.93, 128.99, 133.32, 135.84,
137.68, 138.51, 145,39, 206.57 (C=O). Anal. Calcd for C31H27NO4:
C, 77.97; H, 5.70; N, 2.93. Found: C, 77.88; H, 5.61; N, 2.89%.
(2-Hydroxy-5-nitro-4,6-bis(4-nitrophenyl)-2-phenylcyclohexyl)
(phenyl)methanone 3i: Light yellow solid, m.p. 215–217°C. 1H NMR
(500MHz, CDCl3)δ = 2.33–2.36(dd, 1H, Hb, J1 = 14.5Hz, J2 = 4.0Hz),
2.44–2.47 (t, 1H, Hc, J = 13.5Hz), 4.44–4.46 (dt, 1H, Hd, J1 = 11.5Hz,
J2 = 3.5Hz), 4.52–4.54 (m, 2H, He, Hf), 5.29 (s, 1H, Ha), 5.33–5.37
(m, 1H, Hg), 7.09–7.58 (m, 14H, aromatic), 7.97 (d, 2H, aromatic,
J = 8.0Hz), 8.24 (d, 2H, aromatic, J = 8.0Hz). 13C NMR (500MHz
CDCl3) δ = 43.63, 44.86, 47.75, 54.56, 74.67, 93.60, 123.99, 124.36,
124.44, 127.85, 127.92, 128.29, 128.50, 128.60, 128.94, 129.29,
134.05, 136.75, 142.37, 143.28, 145.62, 147.67, 147.79, 203.71
(C=O). Anal. Calcd for C31H25N3O8: C, 65.60; H, 4.44; N, 7.40. Found:
C, 65.34; H, 4.21; N, 7.57%.
(4,6-Bis(4-chlorophenyl)-2-hydroxy-5-nitro-2-phenylcyclohexyl)
(phenyl)methanone 3j: White solid, m.p. 170–172°C (lit.22). 1H NMR
(500MHz, DMSO–d6) δ = 1.90 (d, 1H, Hb, J = 11.0Hz), 2.87–2.92
(t, 1H, Hc, J = 13.0Hz), 3.94–3.99 (t, 1H, Hd, J = 11.0Hz), 4.26–4.22
(t, 1H, He, J = 11.5Hz), 4.95 (d, 1H, Hf, J = 11.5Hz), 5.49 (s, 1H, Ha),
5.66–5.70 (t, 1H, Hg, J = 4.0Hz), 6.91–7.54 (m, 18H, aromatic). 13C
NMR (500MHz, DMSO-d6) δ = 43.59, 45.11, 46.84, 54.55, 74.60,
94.98, 125.53, 127.22, 128.00, 128.04, 128.19, 128.74, 128.93,
129.05, 129.29, 129.84, 130.81, 132.59, 132.68, 132.99, 136.96,
138.21, 139.25, 145.52, 200.73 (C=O). Anal. Calcd for C31H25Cl2NO4:
C, 68.14; H, 4.61; N, 2.56. Found: C, 68.34; H, 4.58; N, 2.48%.
(4-Chlorophenyl)(2,4,6-tris(4-chlorophenyl)-2-hydroxy-5-nitrocycl-
ohexyl)methanone 3k: White solid, m.p. 222–224°C. 1H NMR
(500MHz, CDCl3)δ = 2.10–2.14(dd, 1H, Hb, J1 = 14.0Hz, J2 = 3.5Hz),
3.27–3.33 (dt, 1H, Hc, J1 = 13.5Hz, J2 = 2.0Hz), 4.15–4.20 (m, 2H, Hd,
He), 5.08 (d, 1H, Ha, J = 2.0Hz), 5.16–5.18 (t, 1H, Hg, J = 4.0Hz), 5.42
(d, 1H, Hf, J = 12.5Hz), 7.08–7.39 (m, 14H, aromatic), 7.42 (d, 2H,
aromatic, J = 8.5Hz), 7.59 (d, 2H, aromatic, J = 8.5Hz), 12.39 (d, 1H,
aromatic, J = 2.0Hz). 13C NMR (500MHz, CDCl3) δ = 37.26, 41.27,
46.49, 48.53, 75.12, 93.30, 126.08, 126.37, 127.26, 127.38, 128.03,
128.13, 128.44, 128.57, 128.59, 128.91, 129.01, 129.06, 129.21,
129.49, 133.40, 135.53, 135.67, 138.19, 140.35, 144.01, 205.06
(C=O). Anal. Calcd for C31H25Cl2NO4: C, 68.14; H, 4.61; N, 2.56.
Found: C, 68.46; H, 4.67; N, 2.89%.
2-(1H-Indole-3-carbonyl)-5-oxo-3,5-diphenylpent-3-enenitrile 3l:
White solid, m.p. 212–214°C. 1H NMR (500MHz, DMSO–d6)
δ = 3.43–3.47 (m, 1H), 3.71–3.75 (m, 1H), 4.11–4.15 (m, 1H), 5.24
(d, 1H, J = 8.0Hz), 7.22–7.61 (m, 11H), 7.88 (d, 2H, J = 7.5Hz), 8.16
(d, 1H, J = 7.5Hz), 8.82 (d, 1H, J = 3.0Hz), 12.39 (d, 1H, J = 2.0Hz).
13C NMR (500MHz, DMSO-d6) δ = 42.32, 42.43, 46.77, 112.99 (CN),
115.25, 118.35, 121.74, 123.03, 124.05, 125.95, 127.81, 128.35,
128.71, 128.88, 129.13, 129.23, 133.82, 136.78, 137.33, 140.15,
185.07 (C=O), 197.82 (C=O). Anal. Calcd for C26H20N2O2: C, 79.57;
H, 5.14; N, 7.14. Found: C, 79.29; H, 4.99; N, 7.46%.
3-Benzoyl-2,6-bis(4-chlorophenyl)-4-hydroxy-4-phenylcyclohex-
1
ane-1,1-dicarbonitrile 3c: White solid, m.p. 190–192°C. H NMR
(500MHz, CDCl3)δ = 2.25–2.28(dd, 1H, Hb, J1 = 14.8Hz, J2 = 2.8Hz),
2.88–2.94 (dt, 1H, Hc, J1 = 13.8Hz, J2 = 2.5Hz), 3.66 (s, 3H, –OCH3),
3.83 (s, 3H, –OCH3), 4.15–4.19 (dd, 1H, Hd, J1 = 11.5Hz, J2 = 3.0Hz),
4.18 (d, 1H, He, J = 12.0Hz) 4.82 (d, 1H, Hf, J = 12.0Hz), 5.20 (d, 1H,
Ha, J = 2.5Hz), 6.65 (d, 2H, aromatic, J = 8.5Hz), 6.96 (d, 2H,
aromatic, J = 9.0Hz), 7.10–7.13 (m, 1H, aromatic), 7.16–7.19 (m, 2H,
aromatic), 7.24–7.27 (m, 2H, aromatic), 7.35–7.40 (m, 5H, aromatic),
7.50–7.56 (m, 4H, aromatic). 13C NMR (500MHz CDCl3) δ = 40.46,
45.46, 47.79, 49.52, 51.37, 74.46, 113.36 (CN), 113.42 (CN), 124.54,
128.02, 128.06, 128.32, 128.69, 129.03, 129.27, 130.15, 132.00,
134.04, 134.64, 135.48, 136.98, 143.36, 203.58 (C=O). Anal. Calcd
for C33H24Cl2N2O2: C, 71.87; H, 4.39; N, 5.08. Found: C, 71.56;
H, 4.61; N, 4.96%.
3-Benzoyl-4-hydroxy-2,6-bis(4-methoxyphenyl)-4-phenylcyclohex-
1
ane-1,1-dicarbonitrile 3d: White solid, m.p. 200–202°C. H NMR
(500MHz, CDCl3)δ = 2.25–2.29(dd, 1H, Hb, J1 = 14.8Hz, J2 = 2.8Hz),
2.88–2.94 (dt, 1H, Hc, J1 = 13.8Hz, J2 = 2.5Hz), 3.66 (s, 3H, –OCH3),
3.83 (s, 3H, –OCH3), 4.15–4.19 (dd, 1H, Hd, J1 = 11.5Hz, J2 = 3.0Hz),
4.18 (d, 1H, He, J = 12.0Hz) 4.82 (d, 1H, Hf, J = 12.0Hz), 5.20 (d, 1H,
Ha, J = 2.5Hz), 6.65 (d, 2H, aromatic, J = 8.5Hz), 6.96 (d, 2H,
aromatic, J = 9.0Hz), 7.10–7.13 (m, 1H, aromatic), 7.16–7.19 (m, 2H,
aromatic), 7.24–7.27 (m, 2H, aromatic), 7.35–7.40 (m, 5H, aromatic),
7.50–7.56 (m, 4H, aromatic). 13C NMR (500MHz, CDCl3) δ = 40.80,
45.37, 48.83, 49.44, 51.68, 55.11, 55.26, 74.59, 113.91 (CN), 114.01
(CN), 114.04, 114.27, 124.63, 125.65, 127.76, 128.06, 128.13, 128.56,
129.95, 133.63, 137.28, 143.93, 159.97, 160.04, 204.25 (C=O). Anal.
Calcd for C35H30N2O4: C, 77.47; H, 5.57; N, 5.16. Found: C, 77.23;
H, 5.61; N, 5.23%.
3-(3-Chlorobenzoyl)-4-(3-chlorophenyl)-4-hydroxy-2,6-diphenyl-
1
cyclohexane-1,1-dicarbonitrile 3e: White solid, m.p. 186–188°C. H
NMR (500MHz, CDCl3) δ = 1H NMR (500MHz CDCl3) δ = 2.29–2.33
(dd, 1H, Hb, J1 = 15.0Hz, J2 = 2.8Hz), 2.86–2.92 (dt, 1H, Hc, J1 =
13.8Hz, J2 = 2.5Hz), 4.19–4.22 (dd, 1H, Hd, J1 = 12.0Hz, J2 = 2.8Hz),
4.20 (d, 1H, He, J = 12.0Hz), 4.76 (d, 1H, Hf, J = 12.0Hz), 5.02 (d, 1H,
Ha, J = 2.5Hz), 7.13–7.60 (m, 18H, aromatic). 13C NMR (500MHz
CDCl3) δ = 40.52, 46.02, 47.85, 50.04, 51.91, 74.37, 76.78, 77.03,
77.29, 113.43 (CN), 113.58 (CN), 122.78, 125.18, 126.14, 127.85,
128.20, 128.82, 128.91, 129.02, 129.28, 129.52, 129.55, 130.00,
133.29, 133.83, 134.77, 134.97, 135.99, 138.46, 145.80, 202.52
(C=O). Anal. Calcd for C33H24Cl2N2O2: C, 71.87; H, 4.39; N, 5.08.
Found: C, 71.75; H, 4.44; N, 5.26%.
4-Hydroxy-3-(4-methoxybenzoyl)-4-(4-methoxyphenyl)-2,6-diphe-
nylcyclohexane-1,1-dicarbonitrile 3f: White solid, m.p. 194–196°C.
1H NMR (500MHz CDCl3) δ = 2.25–2.28 (dd, 1H, Hb, J1 = 14.8Hz,
J2 = 3.0Hz), 2.88–2.94 (dt, 1H, Hc, J1 = 14.0Hz, J2 = 2.5Hz), 3.70 (s,
3H, –OCH3), 3.77 (s, 3H, –OCH3), 4.20–4.23 (dd, 1H, Hd, J1 = 13.5Hz,
J2 = 3.0Hz), 4.24 (d, 1H, He, J = 12.0Hz), 4.79 (d, 1H, Hf, J = 12.0Hz),
5.38 (d, 1H, Ha, J = 2.0Hz), 6.65 (d, 2H, aromatic, J = 9.0Hz), 6.78
(d, 2H, aromatic, J = 9.0Hz), 7.15–7.16 (m, 3H, aromatic), 7.39–7.52
(m, 9H, aromatic), 7.59 (d, 2H, aromatic, J = 7.0Hz). 13C NMR
(500MHz, CDCl3) δ = 41.04, 46.17, 48.02, 50.27, 50.74, 55.21, 55.44,
74.24, 113.43 (CN), 113.82 (CN), 113.86, 125.85, 128.62, 128.87,
128.91, 129.06, 129.14, 130.05, 130.87, 133.83, 136.27, 136.52,
158.89, 164.10, 201.69 (C=O). Anal. Calcd for C35H30N2O4: C, 77.47;
H, 5.57; N, 5.16. Found: C, 77.35; H, 5.25; N, 5.32%.
Received 6 January 2011; accepted 24 January 2011
Paper 1100511 doi: 10.3184/174751911X12977065405044
Published online: 23 March 2011
Ethyl 3-benzoyl-1-cyano-4-hydroxy-2,4,6-triphenylcyclohexane-
1
carboxylate 3g: White solid, m.p. 202–204°C. H NMR (500MHz,

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