J. Chem. Sci., Vol. 117, No. 4, July 2005, pp. 323–328. © Indian Academy of Sciences.

Solvent-free microwave-mediated Michael addition reactions

H SURYA PRAKASH RAO* and S JOTHILINGAM

Department of Chemistry, Pondicherry University, Pondicherry 605 014, India
e-mail: hspr@yahoo.com

MS received 23 August 2004; revised 24 January 2005

Abstract. Facile Michael addition of active methylene compounds to α,β-unsaturated carbonyl compounds
takes place on the surface of potassium carbonate under microwave irradiation. Further studies on micro-
wave-mediated Robinson annulations reveal a convenient and facile method for condensation of chalcone
with methylene compounds to furnish cyclohexenones.

Keywords. Michael addition; Robinson annulation; microwave-mediated organic reactions.

1. Introduction “green chemistry”, a reaction should ideally, be con-

ducted under solvent-free conditions with minimal or
Michael addition of carbon nucleophiles to electron- no side-product formation and with utmost atom-
deficient olefins is a classical and fundamental carbon– economy.10 Even though microwave-assisted sol-
carbon bond-forming reaction.1 This reaction and its vent-free Michael addition reactions on BiCl3 or CdI2,11
close variants have been extensively used in organic EuCl3,12 CeCl3.5H2O,13 and alumina14 surfaces are
synthesis.2 Generally, Michael additions are conducted known, there is still room for the discovery of a con-
in a suitable solvent in the presence of a strong base venient and inexpensive method for this important
either at room temperature or at elevated tempera- carbon–carbon bond-forming reaction. In terms of green
tures.3 Due to the presence of the strong base, side chemistry, the reported solvent-free Michael addi-
reactions such as multiple condensations, polymeri- tion reactions have several experimental difficulties.
zations, rearrangements and retro-Michael additions A suitable solvent is required for loading the reac-
are common. These undesirable side reactions decrease tants, viz. the electron-deficient olefin and active
the yields of the target adduct and render their purifica- methylene compound on the solid surface. Further-
tion difficult. Better results can be obtained by em- more, in order to maximize microwave effects, a
ploying weaker bases such as piperidine, quaternary sufficient amount of the solid support has to be used
ammonium hydroxide, tertiary amines etc.4 There have to prepare a thin film and after completion of the re-
been some reports on Michael reactions catalysed by action, a suitable solvent has to be used for washing the
potassium carbonate in organic solvents,5 and water adducts from the solid surface. Such processes are
in the presence of surfactants6 or phase-transfer cata- obviously difficult to scale up. In this context, we
lysts.7 To a large extent, mild bases restrain the for- planned to conduct Michael addition reaction under
mation of side products, thus improving the yield of eco-friendly and environmentally benign solvent-free
the desired Michael adducts. However, there is still conditions, wherein several disadvantages like long
room for improvement in the conventional reaction reaction time and tedious workup can be overcome.
conditions so as to overcome the disadvantages of With this objective we have conducted microwave-
prolonged reaction times and tedious work-ups. Re- assisted Michael addition reaction on potassium car-
cently, non-conventional procedures like conducting bonate surface. Potassium carbonate is a mild base,
the reaction on the surface of a dry medium8 or under inexpensive and water-soluble. Being a polar molecule,
microwave irradiation9 were found to facilitate the it responds to passing microwaves. We reasoned that
Michael reaction. For the purposes of eco-friendly microwave reactions on potassium carbonate have
eco-friendly features such as, (i) no solvent is required
to conduct the reaction, (ii) as potassium carbonate is
*For correspondence water soluble, addition of reaction mixture after com-
323
324 H Surya Prakash Rao and S Jothilingam

pletion to water could dissolve the solid leaving behind power inputs from 450 W to 600 W to lead to lowering
only a water-insoluble product, (iii) potassium carbon- of the yield of adduct (entry 2, table 2). We tried ad-
ate can in principle be recovered by evaporation of sorbing reactants on catalytic amount (5 mol %) of
water. On this premise, we have studied Michael potassium carbonate (entry 3, table 2); but the reaction
addition of some active methylene compounds to did not go to completion even after exposure to micro-
four Michael acceptors viz (i) 1,3-diphenyl-2-propene- waves for 10 min. Michael addition on barium hy-
1-one (chalcone), (ii) phenyl vinyl ketone, (iii) 1,4- droxide surface (entry 4, table 2) led to only 15% yield
diphenyl-2-butene-1,4-dione (dibenzoylethylene), and of the desired product 3a. Instead of solvent-free
(iv) methyl vinyl ketone on potassium carbonate sur- conditions, we tried the reaction in DMSO with a cata-
face under microwave irradiation. Further, we have lytic amount of potassium carbonate. However, the
conducted Robinson annulations on selected ketones yield of adduct 3a was only 31% (entry 5, table 2).
using α,β-unsaturated carbonyl compounds to generate Thus, solvent-free conditions were better than the reac-
cyclohexane rings. tions in a polar aprotic solvent. There was no reaction
when Michael addition was carried out neat without
potassium carbonate or any other solvent (entry 6, table
2. Results and discussion
2), which indicates that the base is necessary for the
Microwave-mediated solvent-free Michael addition reaction even under microwave conditions.
of diethyl malonate 2a to chalcone 1a was first exam- To test the generality of the Michael addition under
ined. A mixture of diethyl malonate 2a and chalcone present conditions, several active methylene com-
1a was adsorbed over activated potassium carbonate pounds 2a–f were condensed with α,β-unsaturated
with the help of a minimum amount of dry di- ketones 1a–f (scheme 1) and the results are presented
chloromethane (DCM); removal of DCM resulted in in table 1. Michael addition of ethyl benzoylacetate 2b
free flowing powder. The resulting powder was ex- and ethyl cyanoacetate 2c to chalcone 1a resulted in
posed to microwave irradiation at 450 W for 7 min, by diastereomeric mixture (1 : 1 in each case) of adducts
which time the transformation of 1a to 3a was com- 3b and 3c in good yields (entries 2 and 3, table 1).
plete. The reaction mixture as such was added to When the reaction was conducted with unactivated
ice water to separate the Michael adduct 3a (scheme ketones such as cyclopentanone 2d, cyclohexanone
1). Results obtained in this study are presented in 2e and acetophenone 2f the yield of adducts 3d–f
table 1. was moderate (entry 4–6, table 1). Thus, as anticipated,
We attempted to change various parameters involved Michael addition works well with carbonyl compounds
in conducting the Michael reaction with the aim of with active methylene groups.
increasing its efficiency. For this purpose conversion Next, we evaluated the effect of electron-with-
of 1a to 3a was taken as a test case (table 2). Increasing drawing Cl group (1b) and electron-donating Me group

X O R2
O K2CO3, MW, 450 W,
+ X
R1
R1 R2 Y 2-10 min., 52-97%.
Y
1a-f 2a-f 3a-k

1a: R1 = R2 = C6H5 3a: R1 = R2 = C6H5, X = Y = COOEt

1b: R1 = 4-ClC6H4, R2 = C6H5 3b: R1 = R2 = C6H5, X = COOEt, Y = COC6H5
1c: R1 = 4-CH3C6H4, R2 = C6H5 3c: R1 = R2 = C6H5, X = COOEt, Y = CN
1d: R1 = C6H5, R2 =COC6H5 3d: R1 = R2 = C6H5, X = CO(CH2)4, Y = H
1e: R1 = C6H5, R2 = H 3e: R1 = R2 = C6H5, X = CO(CH2)5, Y = H
1f: R1 = CH3, R2 = H 3f: R1 = R2 = C6H5, X = COC6H5, Y = H
2a: X = Y = COOEt 3g: R1 = 4-ClC6H4, R2 = C6H5, X = Y = COOEt
2b: X = COOEt, Y = COC6H5 3h: R1 = 4-CH3C6H4, R2 = C6H5, X = Y = COOEt
2c: X = COOEt, Y = CN 3i: R1 = C6H5, R2 = COC6H5, X = Y = COOEt
2d: X = CO(CH2)4, Y = H 3j: R1 = C6H5, R2 = H, X = Y = COOEt
2e: X = CO(CH2)5, Y = H 3k: R1 = CH3, R2 = H, X = Y = COOEt
2f: X = COC6H5, Y = H

Scheme 1.
 Solvent-free microwave-mediated Michael addition reactions 325

Table 1. The reaction of α,β-unsaturated ketones with active methylene compound

in presence of potassium carbonate under microwave irradiation at 450 W.
Time Yield
Entry no R1 R2 X Y Product (min) (%)
1 C6 H 5 C6 H 5 COOEt COOEt 3aa 7 96
2 C6 H 5 C6 H 5 COOEt COC6H5 3bb 2 89
3 C6 H 5 C6 H 5 COOEt CN 3cc 2 92
4 C6 H 5 C6H5 CO(CH2)4 – 3da 10 55
5 C6 H 5 C6H5 CO(CH2)5 – 3ea 10 52
6 C6 H 5 C6 H 5 COC6H5 H 3fd 10 52
7 4-ClC6H4 C6 H 5 COOEt COOEt 3ga 10 88
8 4-CH3C6H4 C6 H 5 COOEt COOEt 3ha 10 82
9 C6 H 5 COC6H5 COOEt COOEt 3ie 10 95
10 C6 H 5 H COOEt COOEt 3jf 4 97
11 CH3 H COOEt COOEt 3kg 4 96
Refs: a[15], b[15], c[16], d[17], e[18], f[19], g[20]

Table 2. Reaction of chalcone 1a with diethyl malonate 2a under micro-

wave irradiation.
Entry no Medium Reagent Power (W) Time (min) Yield (%)
1 – K2CO3 450 7 96
2 – K2CO3 600 20 75
3 – K2CO3 (cat.) 450 10 46
4 – Ba (OH)2 450 15 15
5 DMSO K2 CO3 450 10 31
6 – – 450 20 No reaction

Table 3. Reaction of chalcone 1a with active methylene Recently, Wang and coworkers21 have reported that
compounds 4a–c in presence of potassium carbonate un- mechanochemical Michael addition of ethyl acetoace-
der microwave irradiation at 450 W.
tate 4a to chalcone 1a in the presence of 0.1 equivalent
Entry no R Product Time (min) Yield (%) of potassium carbonate led to quantitative yield of the
1 COOEt 6aa
5 92
adduct 5a, which surprisingly did not undergo further
2 COCH3 6bb 1⋅5 98 intramolecular aldol condensation leading to the ex-
3 COC6H5 6cc 2 93 pected six-cyclic product. On the other hand, when
the same reaction was performed under microwave
Refs: a[17], b[22], c[23]
irradiation, we did not find any adduct 5a or six-cyclic
t-alcohol, but found only Robinson annulated prod-
ucts, the diasteromeric mixture of cyclic-enone 6a
(1c) on the phenyl ring of chalcone towards Michael and its isomeric non-conjugated enones (scheme 2,
addition of diethyl malonate. In both cases, very good table 3). Thus under the influence of microwaves,
yields of adducts 3g and 3h could be obtained showing initially formed adduct undergoes intramolecular aldol
that the subtle electron influences on the enone did condensation followed by dehydration.
not affect the outcome of the reaction (entries 7 and 8, Similarly, the reaction of chalcone 1a with acetyl
table 1). acetone 4b and benzoyl acetone 4c leads to the di-
To further explore this, we have carried out Michael asteromeric mixture of cyclohexenones 6b and 6c
addition of diethyl malonate to dibenzoylethylene respectively in good yields (scheme 2, table 3).
1d, phenyl vinyl ketone 1e and methyl vinyl ketone In conclusion, we have shown in the present study
1f. In all the cases good yield of adducts 3i–k were that facile Michael addition of active methylene com-
obtained under present condition (entries 9–11, table 1). pounds to the α,β-unsaturated carbonyl compounds
326 H Surya Prakash Rao and S Jothilingam

O Ph Ph
O K2CO3, MW, 450 W, 1 R1
+ R1 R
COCH3 Ph
Ph Ph 1.5-5 min., 92-98%.
COCH3 Ph O

1a 4a-c 5a-c 6a-c

1
4a, 5a, 6a: R = COOEt; 4b, 5b, 6b: COCH3; 4c, 5c, 6c: COC6H5.

Scheme 2.

takes place on potassium carbonate surface under dry dichloromethane. To this solution activated pota-
microwave irradiation. Compared to existing methods, ssium carbonate (0.995 mg, 7⋅2 mmol) was added
main advantage of present procedure is shorter reaction and well swirled. The solvent was removed under
times, solvent-free conditions, convenient work-up reduced pressure using a rotatory evaporator. Resulting
and no side product formation. Present method is free-flowing powder was taken in a 25 mL conical flask.
applicable for Robinson annulation to generated cyclo- amd irradiated in the microwave oven at 450 W for
hexenones from suitable substrates. 7 min. After completion of the reaction (TLC), the
reaction mixture was cooled (r.t.), added to ice water
3. Experimental section (10 mL) and the supernatant aqueous layer decanted to
yield 3a (845 mg, 96%). Analytically pure sample
3.1 General was obtained by recrystallization from DCM/hexanes
(2 : 98); m.p. 66–68°C (lit.13 65–57°C).
All reagents and solvents were purchased from E-
Merck and Sisco Chemicals, India. Microwave reac- 3.3 Ethyl 2-benzoyl-5-oxo-3,5-diphenylpentanoate
tions were carried out using Samsung, India; mono- (3b)
mode and multi-power (power source: 230 V, 50 Hz,
microwave frequency: 2450 MHz) microwave oven. Following the above general procedure, chalcone 1a
TLC (pre-coated silica gel 60 F254, Merck) was used (500 mg, 2⋅4 mmol) was transformed to Michael adduct
to monitor the progress of the reaction and the prod- 2b with ethyl benzoylacetate 3b (461 mg, 2⋅4 mmol)
ucts were isolated by short column chromatography on activated potassium carbonate (0⋅995 mg, 7⋅2 mmol)
on silica gel (100–200 mesh, Acme Synthetic Chemi- surface under microwave irradiation at 450 W for
cals, India) using hexanes/dichloromethane (DCM) 2 min. Yield: 855 mg (89%; viscous liquid).
mixture as the eluant. Melting points were noted us-
ing a Gallenkamp melting point apparatus. IR spectra 3.4 Ethyl 2-cyano-5-oxo-3,5-diphenylpentanoate
were recorded as KBr pellets using Bomem MB104 (3c)
spectrometer. The frequencies at which the 1H NMR
and 13C NMR were recorded in CCl4 : CDCl3 (1 : 1) Following the above general procedure, chalcone 1a
with Bruker 300 MHz and the frequencies of 1H NMR (500 mg, 2⋅4 mmol) was transformed to Michael adduct
and 13C NMR were 300 MHz and 75 MHz respectively. 3c with ethyl cyanoacetate 2c (268 mg, 2⋅6 mmol) on
TMS was used as an internal standard. All products activated potassium carbonate (0⋅995 mg, 7⋅2 mmol)
are known and their authenticity was ensured on the surface under microwave irradiation at 450 W for
basis of spectroscopic, analytical data and on compari- 2 min. Yield: 711 mg (92%; viscous liquid).
son with authentic samples. All the asymmetric pro-
ducts obtained in this work are diastereomeric 3.5 2-(3-Oxo-3-phenylpropyl)-1-cyclopentanone
mixtures. (3d)

3.2 Diethyl 2-(3-oxo-1,3-diphenylpropyl)malonate Following the above general procedure, chalcone 1a

(3a) (100 mg, 0⋅48 mmol) was transformed to Michael
adduct 3d with cyclopentanone 2d (42 mg, 0⋅48 mmol)
Chalcone 1a (500 mg, 2⋅4 mmol) and diethyl malo- on activated potassium carbonate (199 mg, 1⋅44 mmol)
nate 2a (386 mg, 2⋅4 mmol) were dissolved in 5 mL surface under microwave irradiation at 450 W for
 Solvent-free microwave-mediated Michael addition reactions 327

10 min. Yield: 77 mg (55%; white solid); m.p. 66–68°C 0⋅42 mmol) on activated potassium carbonate (174 mg,
(lit.13 67°C). 1⋅26 mmol) surface under microwave irradiation at
450 W for 10 min. Yield: 159 mg (95%; viscous liquid).
3.6 2-(3-Oxo-3-phenylpropyl)-1-cyclohexanone
(3e) 3.11 Diethyl 2-(3-oxo-3-phenylpropyl)malonate
(3j)
Following the above general procedure, chalcone 1a
(100 mg, 0⋅48 mmol) was transformed to Michael Following the above general procedure, α,β-unsaturated
adduct 3e with cyclohexanone 2e (47 mg, 0⋅48 mmol) ketone 1e (500 mg, 3⋅8 mmol) was transformed to Mi-
on activated potassium carbonate (199 mg, 1⋅44 mmol) chael adduct 3j with diethyl malonate 2a (615 mg,
surface under microwave irradiation at 450 W for 3⋅8 mmol) on activated potassium carbonate (1⋅573 g,
10 min. Yield: 77 mg (52%; white solid); m.p. 142– 11⋅4 mmol) surface under microwave irradiation at
144°C; (lit.13 148–149°C). 450 W for 4 min. Yield: 1⋅08 g (97%; viscous liquid).

3.7 1,3,5-Triphenyl-1,5-pentanedione (3f) 3.12 Diethyl 2-(3-oxobutyl)malonate (3k)

Following the above general procedure, chalcone 1a Following the above general procedure, α,β-unsaturated
(500 mg, 2⋅4 mmol) was transformed to Michael ad- ketone 1f (200 mg, 2⋅8 mmol) was transformed to Mi-
duct 3f with acetophenone 2f (288 mg, 2⋅4 mmol) on chael adduct 3k with diethyl malonate 2a (457 mg,
activated potassium carbonate (0⋅995 mg, 7⋅2 mmol) 2⋅8 mmol) on activated potassium carbonate (1⋅16 mg,
surface under microwave irradiation at 450 W for 8⋅4 mmol) surface under microwave irradiation at
10 min. Yield: 410 mg (52%; white solid); m.p. 82– 450 W for 4 min. Yield: 629 mg (96%; viscous liquid).
84°C; (lit.15 81–83°C).
3.13 Ethyl 2-oxo-4,6-diphenyl-3-cyclohexene-1-
3.8 Diethyl 2-[3-(4-chlorophenyl)-3-oxo-1-phenyl- carboxylate (6a)
propyl]malonate (3g)
Following the above general procedure, chalcone 1a
Following the above general procedure, α,β-unsaturated (100 mg, 0⋅48 mmol) was transformed to cyclohex-
ketone 1b (100 mg, 0⋅41 mmol) was transformed to enone 6a with ethyl acetoacetate 4a (62⋅5 mg,
Michael adduct 3g with diethyl malonate 2a (66 mg, 0⋅48 mmol) on activated potassium carbonate (199 mg,
0⋅41 mmol) on activated potassium carbonate (170 mg, 1⋅44 mmol) surface under microwave irradiation at
1⋅23 mmol) surface under microwave irradiation at 450 W for 5 min. Yield: 142 mg (92%; pale yellow vis-
450 W for 10 min. Yield: 146 mg (88%; viscous liquid). cous liquid).

3.9 Diethyl 2-[3-(4-methylphenyl)-3-oxo-1-phenyl- 3.14 6-Acetyl-3,5-diphenyl-2-cyclohexen-1-one

propyl]malonate (3h) (6b)

Following the above general procedure, α,β-unsaturated Following the above general procedure, chalcone 1a
ketone 1c (100 mg, 0⋅45 mmol) was transformed to (100 mg, 0⋅48 mmol) was transformed to cyclohex-
Michael adduct 3h with diethyl malonate 2a (72⋅5 mg, enone 6b with acetylacetone 4b (48 mg, 0⋅48 mmol)
0⋅45 mmol) on activated potassium carbonate (186 mg, on activated potassium carbonate (199 mg, 1⋅44 mmol)
1⋅35 mmol) surface under microwave irradiation at surface under microwave irradiation at 450 W for
450 W for 10 min. Yield: 141 mg (82%; viscous liquid). 1 min 30 s. Yield: 137 mg (98%; pale yellow viscous
liquid).
3.10 Diethyl 2-(1-benzoyl-3-oxo-3-phenylpropyl)
malonate (3i) 3.15 6-Benzoyl-3,5-diphenyl-2-cyclohexen-1-one
(6c)
Following the above general procedure, α,β-unsaturated
ketone 1d (100 mg, 0⋅42 mmol) was transformed to Following the above general procedure, chalcone 1a
Michael adduct 3i with diethyl malonate 2a (68 mg, (500 mg, 2⋅4 mmol) was transformed to cyclohexe-
328 H Surya Prakash Rao and S Jothilingam

none 6c with benzoylacetone 4c (389 mg, 2⋅4 mmol) and Kim S M 2001 Tetrahedron Lett. 42 6299; (c)
on activated potassium carbonate (199 mg, 1⋅44 mmol) Dere R T, Pal R R, Patil P S and Salunkhe M M 2003
Tetrahedron Lett. 44 5351
surface under microwave irradiation at 450 W for
8. (a) Ranu B C and Bhar S 1992 Tetrahedron 48 1342;
2 min. Yield: 789 mg (93%; pale yellow viscous liq- (b) Ranu B C, Bhar S and Sarkar D C 1991 Tetrahe-
uid). dron Lett. 32 2811
9. Romanova N N, Gravis A G, Sharidullina G M,
Acknowledgments Leshcheva I F and Bundel Y G 1997 Mendeleev
Commun. 213
10. Nagendrappa G 2002 Resonance 59
SJ thanks Council of Scientific and Industrial Res- 11. Baruah B, Boruah A, Prajapati D and Sandhu J S
earch for a fellowship. HSPR thanks the UGC-SAP 1997 Tetrahedron Lett. 38 1449
program, DST-FIST program and CSIR, India, for 12. Soriente A, Spinella A, Rosa M D, Giordano M and
financial support. We thank Professor A Srikrishna, Scettri A 1997 Tetrahedron Lett. 38 289
IISc, for recording spectral data and helpful discus- 13. Boruah A, Baruah M, Prajapati D and Sandhu J S
sions. 1998 Synth. Commun. 28 653
14. (a) Ranu B C, Guchhait S K, Ghosh K and Patra A
2000 Green Chem. 5; (b) Patonay T, Varma R S,
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