Efficient method for the synthesis of Michael adducts using Kaolin preloaded with KOH

Article abstract of DOI:10.1080/00397910802439191

Michael addition of various active methylene compounds to β-nitrostyrenes is efficiently catalyzed by using Kaolin preloaded with KOH in acetonitrile at room temperature with moderate to good yields. Copyright Taylor & Francis Group, LLC.

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Efficient Method for the
Synthesis of Michael Adducts
Using Kaolin Preloaded with
KOH
G. Srihari a & M. Marthanda Murthy a
a Organic Chemistry Division II, Indian Institute of
Chemical Technology , Hyderabad, India
Published online: 29 Jan 2009.
To cite this article: G. Srihari & M. Marthanda Murthy (2009) Efficient Method
for the Synthesis of Michael Adducts Using Kaolin Preloaded with KOH, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 39:5, 896-906, DOI: 10.1080/00397910802439191
To link to this article: http://dx.doi.org/10.1080/00397910802439191
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Synthetic Communications1, 39: 896–906, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802439191
Efficient Method for the Synthesis of Michael
Adducts Using Kaolin Preloaded with KOH
G. Srihari and M. Marthanda Murthy
Organic Chemistry Division II, Indian Institute of Chemical Technology,
Hyderabad, India
Abstract: Michael addition of various active methylene compounds to
b-nitrostyrenes is efficiently catalyzed by using Kaolin preloaded with KOH in
acetonitrile at room temperature with moderate to good yields.
Keywords: Active methylene compounds, kaolin=KOH, Michael reaction,
nitrostyrenes
INTRODUCTION
Michael addition products have a wide range of applications in synthetic
organic chemistry. In particular, Michael addition of active methylene
compounds to nitro styrenes afforded nitro alkanes. The nitro group is
converting into different functionalities[1] such as Nef reaction, Meyer
reaction, reduction to amino group, and conversion into the nitrile oxide
for 1,3-dipolar cycloaddition reactions. These nitrogen-containing com-
pounds are much more useful in pharmaceutical and agrochemical
sectors.[2] The Michael reactions have numerous applications in the elegant
synthesis of fine chemicals and are classically catalyzed by bases or suitable
combinations of amines and carboxylic or Lewis acids under homogeneous
conditions. The employment of these bases in the reactions encounters
environmental problems. There has been increasing attention on the design
and use of environmentally compatible solid base catalysts.[3]
Received June 23, 2008.
Address correspondence to M. Marthanda Murthy, Organic Chemistry
Division II, IICT, Tarnaka 500007, India. E-mail: marthanda52@yahoo.com
896

Michael Addition Reaction
897
Different groups reported the Michael addition under homogeneous
conditions, like AgoTf-PPh3 complex in water[4] and polymer-anchored
metal catalyst in different solvents,[5] and workup procedures are typical
in homogeneous medium. Nowadays, heterogeneous catalyst plays an
important role in various organic transformations. Recently the Michael
[6]
reaction was reported by using acidic Al2O3 and different chiral
catalysts.[7]
There are several advantages of engaging a supported reagent in
organic synthesis. They offer remarkable ease of handling and use.
Alumina, silica, and aluminosilicates (clays and zeolites) are some of
the most widely employed supports, where surface hydroxyl groups play
a major role in these reactions. Surface acidity of clays can be reduced
substantially by introducing inorganic bases such as NaOH and KOH.
These modified clays are highly basic and can be employed for base-
catalyzed reactions. Recent years have witnessed a phenomenal growth
in the use of high-surface-area inorganic solids as reaction media for
organic transformations.[8]
In our ongoing research on heterogeneous systems, we found that
Kaolin preloaded with potassium hydroxide (KOH)[9] is an efficient cat-
alyst for Michael reactions in acetonitrile. This method is very simple,
efficient, and suitable for large-scale operations.
RESULTS AND DISCUSSIONS
In general, the reaction has been carried by taking the two components
(nitrostyrenes and active methylene compound in acetonitrile) and
adding a catalytic amount of Kaolin=KOH. The mixture was stirred at
room temperature (Scheme 1), which afforded the corresponding Michael
adducts in moderate to good yields.
Scheme 1. Synthesis of Michael adducts.

898
G. Srihari and M. M. Murthy
Entry a was taken as a representative example for comparing
reaction rates in various solvents such as dichloromethane (DCM),
acetonitrile (CH3CN), N,N-dimethyl formamide (DMF), dimethylsulfoxide
(DMSO), methanol (MeOH), and water. No product formation was
observed in DCM, DMF, DMSO, and water even under reflux condi-
tions. The reaction progressed smoothly in the case of methanol and acet-
onitrile, and better yields were observed in acetonitrile. After optimizing
the condition, we next applied the generality of addition of various
nitrostyrens to active methylene compounds and results obtained are
listed in Table 1. The products obtained are diastereomers (1:1 mixture)
in the case of ethyl acetoacetate and ethyl benzoylacetate, whereas in the
case of malanonitrile the products are racemic.
We screened various nitrostyrenes with malanonitrile, ethyl acetoace-
tate, and ethyl benzoylacetate. Electron-donating groups on aryl nitrostyr-
enes take longer than unsubstituted nitrostyrenes. The products were
identified by spectroscopy [1H NMR, infrared (IR), and mass spectroscopy
(MS)] or otherwise compared with known compounds. The procedure
described in this article was found to be more effective than those described
in earlier reports.
CONCLUSION
In conclusion, we have developed a simple, convenient, and practical method
for the synthesis of Michael adducts by using Kaolin preloaded with KOH.
EXPERIMENTAL
General Procedure for Synthesis of Michael Adducts
A mixture of nitro styrenes (1 mmol), active methylene compounds
(1.2 mmol), and a catalytic amount of Kaolin=KOH taken in acetonitrile
(2 mL) was stirred at room temperature for the appropriate time as men-
tioned in Table 1. The reaction was monitored by thin-layer chromato-
graphy (TLC). The product was filtered, and the crude product was
purified by column chromatography.
General Procedure for the Preparation of Solid Support Preloaded
with Base
Kaolin clay (3 g) was added to 4 ml of 25% KOH solution, and the mix-
ture was sonicated for a period of 4 h, then dried in a rotary evaporator

Michael Addition Reaction
899
Table 1. Conjugate addition of active methylene compounds to nitrostyrenes
Nitro styrene
R
Active methylene
compound
Entry
a
Producta Time (h) Yieldb (%)
1
3a
2.5
79
b
c
1
1
1
3b
3c
3d
4.0
3.2
3.8
82
80
80
d
e
f
1
3e
4f
3.0
2.6
77
82
2a
g
2a
2a
4g
4h
2.8
3.5
81
77
h
i
j
2a
2a
4i
4j
3.3
3.0
85
76
(Continued )

900
G. Srihari and M. M. Murthy
Table 1. Continued
Nitro styrene
R
Active methylene
compound
Entry
k
Producta Time (h) Yieldb (%)
2a
4k
3.2
68
l
2b
4l
2.0
73
m
n
2b
2b
4m
4n
2.5
3.0
71
70
1
aAll products were characterized by IR, H NMR, and mass spectroscopy.
bUnoptimized, isolated yields.
for several hours (obtaining solid support with suitable residual water).
Residual traces of water were removed from the support by irradiating
with microwaves for 15 min. The solid was ground to a powder. The solid
support thus prepared contains about 6 mmol of KOH per gram.
Spectral Data of Compounds
Compound 3a
Viscous oil. IR (KBr): 2930, 2225, 1610, 1560, 1455; 1H NMR (200 MHz,
CDCl3): d ¼ 7.49–7.30 (m, 5H), 4.98–4.88 (m, 2H), 4.40 (d, 1H), 4.10–4.02
(m, 1H); ESI-MS: 215 ([M]þ).

Michael Addition Reaction
901
Compound 3b
Viscous oil. IR (KBr): 2919, 2228, 1611, 1557, 1514, 1256, 1181; 1H NMR
(300 MHz, CDCl3): d ¼ 7.25–6.90 (m, 4H), 4.95–4.75 (m, 2H), 4.35 (d,
1H), 4.05–3.98 (m, 1H), 3.82 (s, 3H); ESI-MS: 245 ([M]þ).
Compound 3c
1
Solid. Mp 99–101 ꢀC; IR (KBr): 2921, 2253, 1611, 1555, 1514, 1435; H
NMR (300 MHz, CDCl3): d ¼ 7.30–7.20 (m, 4H), 5.01–4.80 (m, 2H),
4.38 (d, 1H), 4.05–3.95 (m, 1H), 2.40 (s, 3H); ESI-MS: 229 ([M]þ).
Compound 3d
Solid. Mp 95–97 ꢀC; IR (KBr): 2919, 2257, 1604, 1556, 1495, 1436, 1252;
1H NMR (300 MHz, CDCl3): d ¼ 7.45–7.40 (m, 1H), 7.28–7.20 (m, 1H),
7.09–6.95 (m, 2H); ESI-MS: 245 ([M]þ).
Compound 3e

902
G. Srihari and M. M. Murthy
1
Solid. Mp 115–117 ꢀC; IR (KBr): 2923, 2202, 1645, 1554, 1410, 1376; H
NMR (200 MHz, CDCl3): d ¼ 7.40–7.01 (m, 3H), 4.95–480 (m, 2H), 4.55–
4.40 (m, 2H); ESI-MS: 244 ([M þ Na]þ).
Compound 4f
1
Solid. Mp 93–94 ꢀC; IR (KBr): 2925, 1736, 1632, 1562, 1493, 1381; H
NMR (300 MHz, CDCl3): d ¼ 7.30–7.20 (m, 3H), 7.18–7.12 (m, 2H),
4.78–4.68 (m, 2H), 4.25–4.09 (m, 2.5H), 3.90–4.01 (m, 1.5H), 2.30 (s,
1.5H), 2.04 (s, 1.5H), 1.28 (t, 1.5H), 1.01 (t, 1.5H); ESI-MS: 279 ([M]þ).
Compound 4g
Viscous oil. IR (KBr): 2922, 1739, 1718, 1556, 1374; 1H NMR (200 MHz,
CDCl3): d ¼ 7.35 (s, 1H), 6.28 (s, 1H), 6.18 (d, 1H), 4.81–4.68 (m, 2H),
4.38–4.02 (m, 4H), 2.30 (s, 1.5H), 2.15 (s, 1.5H), 1.28 (t, 1.5H), 1.18 (t,
1.5H); ESI-MS: 269 ([M]þ).
Compound 4h
1
Viscous oil. IR (KBr): 2980, 1741, 1717, 1611, 1555, 1514; H NMR
(300 MHz, CDCl3): d ¼ 7.09 (d, 2H), 6.78 (d, 2H), 4.77–4.63 (m, 2H),

Michael Addition Reaction
903
4.25–3.90 (m, 4H), 3.75 (s, 3H), 2.28 (s, 1.5H), 2.05 (s, 1.5H), 1.25 (t,
1.5H), 1.05 (t, 1.5H); ESI-MS: 309 ([M]þ).
Compound 4i
Viscous oil. IR (KBr): 2983, 1739, 1717, 1554, 1375; 1H NMR (200 MHz,
CDCl3): d ¼ 7.15–7.02 (m, 4H), 4.76–4.64 (m, 2H), 4.25–3.95 (m, 4H),
2.32 (s, 3H), 2.26 (s, 1.5H), 2.02 (s, 1.5H), 1.25 (t, 1.5H), 1.05 (t, 1.5H);
ESI-MS: 316 ([M þ Na]þ).
Compound 4j
Solid. Mp 107–108 ꢀC; IR (KBr): 2924, 1738, 1561, 1375; 1H NMR
(200 MHz, CDCl3): d ¼ 7.85–7.67 (m, 4H), 7.53–7.42 (m, 2H), 7.35–7.27
(m, 1H), 4.92–4.81 (m, 2H), 4.40–4.31 (m, 3H), 3.98–3.89 (m, 1H), 2.30 (s,
1.5H), 2.07 (s, 1.5H), 1.28 (t, 1.5H), 0.91 (t, 1.5H); ESI-MS: 352 ([M þ Na]þ).
Compound 4k
Viscous oil. IR (KBr): 2981, 1717, 1597, 1553; 1H NMR (300 MHz,
CDCl3): d ¼ 7.29–7.19 (m, 1H), 7.15–7.01 (m, 1H), 6.91–6.84 (m, 2H),

904
G. Srihari and M. M. Murthy
4.95– 4.69 (m, 2H), 4.35– 4.19 (m, 4H), 3.90 (s, 1.5H), 3.85 (s, 1.5H), 2.30
(s, 1.5H), 2.02 (s, 1.5H), 1.28 (t, 1.5H), 0.98 (t, 1.5H), ESI-MS: 309
([M]þ).
Compound 4l
1
Solid. Mp 79–80 ꢀC; IR (KBr): 2924, 1726, 1686, 1597, 1551; H NMR
(200 MHz, CDCl3): d ¼ 8.05–7.89 (m, 2H), 7.61–7.45 (m, 4H), 7.31–7.18
(m, 4H), 4.95–4.88 (m, 2H), 4.76 (d, 1H), 4.50–4.38 (m, 1H), 4.20–4.06 (q,
1H), 3.90–3.79 (q, 1H), 1.21 (t, 1.5H), 0.92 (t, 1.5H); ESI-MS: 341 ([M]þ).
Compound 4m
Viscous oil. IR (KBr): 2923, 1735, 1685, 1555; 1H NMR (200MHz, CDCl3):
d ¼ 8.08–7.95 (m, 2H), 7.65–7.35 (m, 4H), 6.30–6.09 (m, 2H), 5.05–4.85 (m,
2H), 4.80–4.75 (m, 1H), 4.60–4.48 (m, 1H), 4.20–4.11 (q, 1H), 4.08–3.95 (q,
1H), 1.18 (t, 1.5H), 1.07 (t, 1.5H); ESI-MS: 354 ([M þ Na]þ).
Compound 4n
Viscous oil. IR (KBr): 2924, 1735, 1684, 1611, 1553; 1H NMR (200 MHz,
CDCl3): d ¼ 8.07–7.98 (m, 1H), 7.86–7.78 (m, 1H), 7.65–7.40 (m, 3H),

Michael Addition Reaction
905
7.20–7.08 (m, 2H), 6.85–6.70 (m, 2H), 4.90–4.82 (m, 2H), 4.75–4.68 (m,
1H), 4.40–4.30 (m, 1H), 4.20– 4.10 (q, 1H), 3.95–3.82 (q, 1H), 3.75 (s,
1.5H), 3.68 (s, 1.5H), 1.19 (s, 1.5H), 0.92 (s, 1.5H); ESI-MS: 394 ([M]þ).
ACKNOWLEDGMENT
We thank Dr. J. S. Yadav (director) and Dr. V. V. N. Reddy (head of
department) of the Indian Institute of Chemical Technology, Hyderabad,
for constant encouragement and financial support.
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