Application of microwaves in organic synthesis: A rapid and efficient synthesis of new 3-aryl-2-imino-4-methyl-2,5-dihydrofurans and 3-aryl-3-2-(5H)-furanones

Article abstract of DOI:10.1081/SCC-120018778

New 3-aryl-2-imino-4-methyl-2,5-dihydrofurans (3a-f) were efficiently synthesized by a one-pot condensation under focused microwave irradiation from simple and readily available starting materials. Hydrolysis of (3a-f) gave 3-aryl-4-methyl-2-(5H)-furanones (4a-f).

Full text of DOI:10.1081/SCC-120018778

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Application of Microwaves in Organic Synthesis:
A Rapid and Efficient Synthesis of New 3-Aryl-2-
imino-4-methyl-2,5-dihydrofurans and 3-Aryl-3-2-(5H)-
furanones
a
a b
Didier Villemin & Liang Liao
a
Ecole Nationale Supérieure d'Ingénieurs de Caen , ISMRA , Cedex, France
Clark Atlanta University, Department of Chemistry , Atlanta, Georgia, USA
b
Published online: 16 Aug 2006.
To cite this article: Didier Villemin & Liang Liao (2003) Application of Microwaves in Organic Synthesis: A Rapid and Efficient
Synthesis of New 3-Aryl-2-imino-4-methyl-2,5-dihydrofurans and 3-Aryl-3-2-(5H)-furanones, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 33:9, 1575-1585, DOI: 10.1081/SCC-120018778
To link to this article: http://dx.doi.org/10.1081/SCC-120018778
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Õ
SYNTHETIC COMMUNICATIONS
Vol. 33, No. 9, pp. 1575–1585, 2003
Application of Microwaves in Organic Synthesis:
A Rapid and Efficient Synthesis of New
3
-Aryl-2-imino-4-methyl-2,5-dihydrofurans
and 3-Aryl-3-2-(5H )-furanones
1
,
1,2
Didier Villemin * and Liang Liao
1
Ecole Nationale Superieure d’Ingenieurs de Caen,
´ ´
ISMRA, Cedex, France
2
Clark Atlanta University, Department of Chemistry,
Atlanta, Georgia, USA
ABSTRACT
New 3-aryl-2-imino-4-methyl-2,5-dihydrofurans (3a–f ) were effi-
ciently synthesized by a one-pot condensation under focused micro-
wave irradiation from simple and readily available starting materials.
Hydrolysis of (3a–f ) gave 3-aryl-4-methyl-2-(5H )-furanones (4a–f ).
*
Correspondence: Didier Villemin, Ecole Nationale Superieure d’Ingenieurs
´ ´
de Caen, ISMRA, UMR CNRS 6507, F-14050 Caen Cedex, France;
Fax: (33)231452877; E-mail: didier.villemin@ismra.fr.
1
575
DOI: 10.1081/SCC-120018778
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

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1
576
Villemin and Liao
Key Words: Microwave; Lactone; Iminolactone.
2
Butenolides and particularly Á -butenolides (but-2-en-4-olides) or
[
(5H )-furanones form an important class of natural products that
1]
2
are biologically active compounds. Many butenolides have a potential
[
use in medicine and in agriculture (vitamin C, acetogenins, cardiotonic
2]
[
3]
[4]
steroids, antibacterial, insecticides, herbicides, and plant-growing
[5]
[6]
[7]
[1]
regulator ). The chemistry and the photochemistry of 2(5H )-fura-
[8]
nones are well known, but to our knowledge the iminolactone derivatives
2
of these Á -butenolides have not been previously described. We were
[
9]
interested in the synthesis of biologically active butenolides and in the
development of new synthetic methodologies using focused microwave
[10]
irradiation.
We reportherein an efficientand rapid syn ht esis of 3-aryl-2-imino-
-methyl-2,5-dihydrofurans under microwave irradiation (Sch. 1). A mix-
4
ture of a-ketol (1a–c) (1 equiv.), substituted phenylacetonitrile (1 equiv.),
and a solution of sodium ethoxide in ethanol was irradiated by micro-
[
11]
waves (2450 MHz) at100 W for 2 min in a resonance cav iyt MES
producing new 3-aryl-2-imino-4-methyl-2,5-dihydrofurans (3a–f ) with a
7
0–83% yield (see Table 1).
The new iminofurans have melting points lower than the correspond-
À1
ing lactams. The infrared absorption (ꢀ C¼N: 1649–1666-cm ) and the
CMR spectra of (3) are in agreement with the structure iminolactone
(
These iminofuranones (3a–f ) have been hydrolyzed with aqueous
ꢁ C¼N: 156.4–159.3 ppm) (Sch. 2).
hydrochloric acid for 2 h (Sch. 3) producing lactone (4a–f ). The
hydrolysis also took place under microwave irradiation (reflux, 15 min).
The yields obtained for lactones were 63–83% and are reported in
Table 2. Under microwave activation, a one-pot two step reaction is
Scheme 1. Formation of new 3-aryl-2-imino-4-methyl-2,5-dihydrofurans (3a–f ).

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Application of Microwaves in Organic Synthesis
1577
Table 1. 3-Aryl-2-imino-4-methyl-2,5-dihydrofurans (3a–f ) obtained.
1
R
2
R
Product
Ar
Yield (%)
3a
3b
3c
3d
3e
3f
–CH3 –CH3
–C H
6
80
79
83
74
70
79
5
–CH
–CH
3
–CH
–C
3
–(4-Cl)C
–(4-Cl)C
6
6
H
H
4
3
2
H
5
4
–CH3 –CH3
–CH3 –CH3
–(4-OMe)C H
6 4
–(3,4-diOMe)C H
6
3
–(CH
2
)
5
–
6 5
–C H
Scheme 2. Comparison between iminolactone (3a–b) and lactam (5a–b).
Scheme 3. Hydrolysis of iminolactone (3a–f ) into lactone (4a–f ).
Table 2. 3-Aryl-4-methyl-2-(5H )-furanones (4a–f ) obtained.
1
2
Product
R
R
Ar
Yield (%)
4a
4b
4c
4d
4e
4f
–CH3 –CH3
–C H
6
64
83
67
60
67
63
5
–CH
–CH
3
3
–CH
–C
3
–(4-Cl)C
–(4-Cl)C
6
H
H
4
2
H
5
6
4
–CH3 –CH3
–CH –CH
–(CH
–(4-OMe)C H
6 4
3
3
–(3,4-diOMe)C
–C
6 3
H
2
)
5
–
6 5
H

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578
Villemin and Liao
possible after condensation. The hydrolysis is performed in the same pot
under focused irradiation for 20 min. The global yield is about the same
as a two step reaction with a classic hydrolysis but the one-pot procedure
is simpler and shorter than the two steps procedure.
The rearrangementof ( 3a) to lactam (5a) in concentrated sulfuric
[
12]
acid was not observed whatever the conditions.
nofuranones (3a–f ) can be obtained under classical conditions (reflux,
h), the use of focused microwave allows these lactones to be obtained
Although these imi-
4
quickly with a superior yield and purity than the reaction performed
under classic heating.
The suggested mechanism for the formation of iminolactam (3a–f )
begins by the addition of the alcoholate on the nitrile group followed by a
Knoevenagel reaction leading to ring formation according to Sch. 4.
It was noticed that the ease of ring formation was due to the presence
[
14]
of a gem-dialkyl producing a Thorpe-Ingold conformational effect
which states that alkyl substitution on a central methylene causes com-
pression of the internal angle that leads to an easier ring formation.
[
15]
Recently LeBigot et al. have reported
a reaction close to the
formation of iminolactones (3a–f ): the formation of iminocoumarin by
the condensation of nitrile with salicyladehyde.
In conclusion, new 3-aryl-2-imino-4-methyl-2,5-dihydrofurans (3a–f )
and 3-aryl-4-methyl-2(5H )-furanones (4a–f ) were efficiently synthesized
Scheme 4. The lack of isomerization of (3a) in presence of sulfuric acid.
Scheme 5. Mechanism of formation of 3-aryl-2-imino-4-methyl-2,5-dihydrofurans.

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Application of Microwaves in Organic Synthesis
1579
under focused microwave irradiation from simple and readily available
starting materials.
EXPERIMENTAL
1
The C NMR spectra were recorded with a Bruker AC 250 spectro-
3
meter at 62.89 MHz, in CDCl using TMS as internal standard (proton
3
decoupled, JCP given in Hz). The IR spectra were recorded as KBr pellets
on Perkin Elmer 16 PC FT–IR spectrometer and frequencies are given
À1
in cm . The mass spectra were obtained on a Nermag Riber R10-10H
with a 70 eV electron impact ionization. Uncorrected melting points were
determined with a Kofler hot-stage apparatus and are Microwave irra-
diation’s were carried out in a microwave resonance cavity (cavity EO13
of MES).
Synthesis of 3-Aryl-2-imino-4-methyl-2,5-dihydrofurans
Method A (Under Microwave)
A mixture of 3-hydroxy-3-methyl-butan-2-one (306 mg, 3 mmol), and
phenylacetonitrile (352 mg, 3 mmol) with a solution of sodium ethoxide
(
2
3 mmol) in ethanol (1.9 mL) was irradiated by microwaves (100 W) for
min, after which the solvent was removed by evaporation. The product
was purified by silica gel chromatography (eluant: EtOH/CH Cl : 2/98).
2
2
A pale yellow oil was obtained (470 mg, yield 77.8%). The oil was
subsequently dried under reduced pressure and after a period of 20 days
ꢀ
at20 C, a pure white product was obtained.
Method B (Under Classical Conditions)
A mixture of 3-hydroxy-3-methyl-butan-2-one (306 mg, 3 mmol) and
phenylacetonitrile (352 mg, 3 mmol) with a solution of sodium ethoxide
ꢀ
(
3 mmol) in ethanol (1.9 mL) was stirred to ambient temperature (20 C)
during 24 h. After evaporation of the solvent, the mixture was purified as
above in the method A (483 mg, yield 80%).
2-Imino-4,5,5-trimethyl-3-phenyl-2,5-dihydrofuran (3a): This product
was obtained from 3-hydroxy-3-methyl-butan-2-one and phenylacetoni-
ꢀ
trile in a yield of 80%. White solid, m.p.: 49–50 C. Anal. Found: H 7.62,
1
C 77.46; C H NO requires H 7.51, C 77.58. H NMR (CDCl ) ꢁ : 1.49
1
3
15
3
H

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Villemin and Liao
(
H
6H, s, 2 Â CH ), 1.95 (3H, s, CH ), 6.10 (1H, s, N–H), 7.34–7.45 (5H, m,
3
3
1
3
). C NMR (CDCl ) ꢁ : 11.31 (C¼C–CH ), 25.05 (2 Â CH ), 87.78
arom
3
C
3
3
(
(
(
1
2
1
9
C ), 127.39 (C ), 128.14 (C
5
), 128.53 (C
Carom3,5), 131.24 (Carom1), 157.35 (C¼N). IR (KBr) ꢀ
), 128.90 (C ), 129.16
3
4
arom4
arom2,6
À1
cm : 3290
NH), 2976, 2932, 1652 (C¼N), 1492, 1438, 1386, 1358, 1304, 1262,
max
164, 1134, 1066, 982, 888, 820, 772, 700. MS EI m/z (%): 202 (26.8),
þꢀ
01 (M , 62), 186 (16), 177 (11), 175 (48), 160 (32), 159 (73), 158 (22),
57 (22), 143 (23), 141 (12), 131 (40), 128 (16), 123 (14), 116 (16), 115 (39),
8 (28), 92 (20), 91 (50), 87 (22), 77 (34), 72 (35), 57 (28), 51 (28), 43 (100).
3
-(4-Chloro-phenyl)-2-imino-4,5,5-trimethyl-2,5-dihydrofuran
(3b):
This product was obtained from 3-hydroxy-3-methyl-butan-2-one
(
the yield of 79%. Yellow solid, m.p.: 90–91 C. Anal. Found: H 6.01, C
306 mg, 3 mmol) and (4-chlorophenyl)acetonitrile (455 mg, 3 mmol) in
ꢀ
1
6
6.18; C H ClNO requires H 5.99, C 66.24. H NMR (CDCl ) ꢁ : 1.48
13 14 3 H
(
6H, s, 2 Â CH ), 1.95 (3H, s, CH ), 6.75 (1H, s, NH), 7.34 (2H, d,
3
3
3
3
13
). C NMR
arom
J
¼ 8.4 Hz, H
), 7.42 (2H, d, J ¼ 8.4 Hz, H
HH
HH
arom
(
(
CDCl ) ꢁ : 11.38 (C¼C–CH ), 24.99 (2 Â CH ), 87.83 (C ), 126.48
3
C
3
3
5
C ), 128.71 (C
3
), 129.19 (C ), 129.70 (C
4
), 130.56 (C
),
arom3,5
arom2,6
arom4
À1
1
2
1
2
34.03 (Carom1), 157.84 (C¼N). IR (KBr) ꢀ
cm : 3280 (N–H),
974, 1664 (C¼N), 1492, 1460, 1386, 1356, 1310, 1166, 1142, 1088,
max
3
7
þ.
ClNO , 32.1),
35 (M , 100), 222 (8.2), 220 (23.4), 200 (10.2), 192 (26.1), 165 (17.3), 142
074, 982, 894, 880, 836. MS EI m/z (%): 237 (C H
14
1
3
þ.
(
16.9), 141 (14.7), 125 (13.0), 115 (32.3), 89 (7.1), 59 (15.8), 43 (100).
-(4-Chloro-phenyl)-5-ethyl-2-imino-4,5-dimethyl-2,5-dihydrofuran (3c):
This product was obtained from 3-hydroxy-3-methyl-pentan-2-one
3
(
the yield of 83%. Yellow solid, m.p.: 56–57 C. Anal. Found: H 6.50, C
348 mg, 3 mmol) and (4-chlorophenyl)acetonitrile (455 mg, 3 mmol) in
ꢀ
1
6
(
3
7.41; C H ClNO requires H 6.46, C 67.33. H NMR (CDCl ) ꢁ : 0.84
14 16 3 H
3
3H, t, J ¼ 7.4 Hz, CH CH ), 1.46 (3H, s, C¼C–CH ), 1.74 (1H, td,
HH
2
3
3
2
3
JHH ¼ 7.4 Hz, J ¼ 14.8 Hz, CH H CH ), 1.88 (1H, td, J ¼ 7.4 Hz,
HH
a
b
3
HH
2
JHH ¼ 14.8 Hz, CH H CH ), 1.90 (3H, s, CH ), 6.75 (1H, s, NH), 7.34
a
b
3
3
3
3
(
1
2H, d,
J
¼ 8.5 Hz, H
), 7.42 (2H, d,
J
¼ 8.5 Hz, H
).
arom
HH
arom
HH
3
C NMR (CDCl ) ꢁ : 7.32 (CH CH ), 11.47 (C¼C–CH ), 23.74
3
C
2
3
3
(
CH ), 30.46 (CH CH ), 90.16 (C ), 127.91 (C ), 128.69 (C
3
),
arom2,6
3
2
3
5
1
29.75 (Carom4), 130.39 (C ), 130.55 (Carom3,5), 134.00 (Carom4), 156.36
4
À1
(
C¼N). IR (KBr) ꢀ
cm : 3284 (N–H), 3052, 2970, 1649 (C¼N),
max
1494, 1452, 1380, 1342, 1256, 1136, 1090, 982, 904, 833, 598. MS EI
m/z (%): 251 (C H ClNO , 10.4), 249 (M , 28.9), 235 (6.0), 234
3
7
þ.
þ.
1
4
16
(
1
36.4), 223 (32.8), 221 (92.2), 208 (5.4), 206 (14.5), 194 (9.5), 192 (26.6),
85 (20.9), 128 (13.4), 115 (20.6), 57 (10.1), 43 (100).
-Imino-3-(4-methoxy-phenyl)-4,5,5-trimethyl-2,5-dihydrofuran (3d):
This product was obtained from 3-hydroxy-3-methyl-butan-2-one
2

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Application of Microwaves in Organic Synthesis
1581
(
306 mg, 3 mmol) and (4-methoxyphenyl)acetonitrile (442 mg, 3 mmol) in
the yield of 74%. Yellow oil. Anal. Found: H 7.43, C 72.52; C H NO
2
1
4
17
1
requires H 7.41, C 72.7. H NMR (CDCl ) ꢁ : 1.48 (6H, s, 2 Â CH ), 1.94
3
H
3
(
3
3H, s, CH ), 3.83 (3H, s, OCH ), 6.00 (1H, s, NH), 6.97 (2H, d,
3
3
3
13
JHH ¼ 8.8 Hz, H
), 7.30 (2H, d, J ¼ 8.8 Hz, Harom). C NMR
HH
arom
(
(
(
(
1
8
1
CDCl ) ꢁ : 11.28 (C¼C–CH ), 24.99 (2 Â CH ), 55.16 (OCH ), 87.53
3
C
3
3
3
C ), 113.98 (C
5
), 118.41 (C ), 123.43 (C ), 126.81 (C
4
), 130.32
cm : 3286
arom2,6
3
arom1
À1
Carom3,5), 156.34 (Carom4), 159.29 (C¼N). IR (KBr) ꢀ
max
N–H), 2976, 2934, 1666, 1660 (C¼N), 1652, 1608, 1574, 1514, 1464,
384, 1364, 1314, 1304, 1290, 1248, 1178, 1168, 1070, 1034, 982, 894,
34. MS EI m/z (%): 232 (21.8), 231 (M , 100), 216 (22.7), 199 (7.9),
87 (33.6), 173 (18.7), 161 (20.4), 146 (9.9), 130 (19.9), 128 (55.1), 127
þ.
(
4
31.9), 115 (8.8), 109 (14.3), 91 (8.2), 81 (10.8), 77 (15.6), 65 (23.7),
3 (56.0).
-Imino-3-(3,4-dimethoxy-phenyl)-4,5,5-trimethyl-2,5-dihydrofuran (3e):
This productwas o ab it ned from 3-hydroxy-3-m he yt l-b au nt -2-one
2
(
306 mg, 3 mmol) and (3,4-dimethoxyphenyl)acetonitrile (532 mg,
ꢀ
3
Found: H 7.37, C 68.90; C H NO requires C H NO , H 7.33, C
6
mmol) in the yield of 74%. Yellow solid, m.p.: 65–66 C. Anal.
1
3
15
15 19
3
1
8.94. H NMR (CDCl ) ꢁ : 1.49 (6H, s, 2 Â CH ), 1.96 (3H, s, CH ),
3
H
3
3
3
.90 (3H, s, OCH ), 3.91 (3H, s, OCH ), 6.60 (1H, s, NH), 6.88–6.95 (3H,
3 3
1
3
m, Harom). C NMR (CDCl ) ꢁ : 11.32 (C¼C–CH ), 25.02 (2 Â CH ),
3
C
3
3
5
1
5.82 (OCH ), 55.85 (OCH ), 87.58 (C ), 111.22 (C ), 112.19,
arom2,6
3
3
5
21.84, 123.75, 127.03, 148.88 (C
À1
), 156.56 (C¼N). IR (KBr) ꢀ
arom3,4
max
cm : 3284 (N–H), 2976, 2934, 2836, 1662 (C¼N), 1604, 1582, 1516,
1464, 1410, 1322, 1266, 1250, 1222, 1140, 1074, 1026, 888, 816. MS EI
m/z (%): 261 (M , 100), 246 (26.8), 230 (39.7), 217 (34.9), 215 (18.4),
þ.
2
4
03 (17.3), 191 (18.8), 187 (16.5), 172 (10.9), 160 (8.1), 145 (7.1), 115 (11.0),
3 (13.2).
4
-Methyl-3-phenyl-1-oxa-spiro[4.5]dec-3-en-2-ylideneamine (3f ): This
product was obtained from 1-(1-hydroxy-cyclohexyl)ethanone (306 mg,
3
Yellow solid, m.p.: 125–126 C. Anal. Found: H 8.01, C 79.58;
mmol) and phenylacetonitrile (352 mg, 3 mmol) in the yield of 79%.
ꢀ
1
C H NO requires C H NO, H 7.94, C 79.63. H NMR (CDCl ) ꢁ :
1
3
15
16 19
3
H
1
6
1
8
1
3
1
1
.21–1.28 (2H, m, CH ), 1.55–1.90 (8H, m, 4 Â CH ), 1.92 (3H, s, CH ),
2
2
3
1
3
.70 (1H, s, N–H), 7.28–7.48 (5H, m, H
). C NMR (CDCl ) ꢁ :
3 C
arom
1.56 (C¼C–CH ), 21.91 (2 Â CH ), 24.74 (CH ), 33.53 (2 Â CH ),
3
2
2
2
9.09 (C ), 127.45 (C ), 127.99 (C
5
), 128.49 (C
29.23 (Carom3,5), 131.32 (Carom1), 157.44 (C¼N). IR (KBr) ꢀ
), 129.01 (C ),
4
3
arom4
arom2,6
À1
cm
:
max
282 (N–H), 2913, 2846, 1666 (C¼N), 1600, 1494, 1446, 1382, 1364, 1292,
þ.
240, 1138, 1096, 980, 940, 864, 850, 766, 698. MS EI m/z (%): 241 (M ,
00), 226 (61.2), 212 (84.4), 198 (24.4), 186 (72.3), 184 (13.6), 170 (21.9),

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582
Villemin and Liao
160 (21.5), 155 (20.8), 141 (17.0), 133 (13.1), 128 (18.4), 115 (63.4), 91
(
18.1), 77 (17.2), 55 (23.0), 43 (13.3).
Synthesis of 3-(Aryl)-4-methyl-2-(5H )-furanones
General Procedure
A mixture of 3-hydroxy-3-methylbutan-2-one (3 mmol), phenylace-
tonitrile (3 mmol), and a solution of sodium ethoxide (3 mmol) in ethanol
(
1.9 mL) were irradiated by focused microwave at 100 W for 2 min. Then
a solution of hydrochloric acid (18%, 1.2 mL) was added and heated at
ꢀ ꢀ
5 C for 2 h or irradiated by focused microwave at 95 C for 30 min. After
9
cooling, the solution was evaporated in a vacuum and the residue
was extracted with ether (30 mL Â 3). After evaporation of ether the
product was purified by silica gel chromatography (eluent: EtOH/
CH Cl : 2/98).
2
2
3-Phenyl-4,5,5-trimethyl-2-(5H )-furanone (4a): This productwas
obtained from 3-hydroxy-3-methylbutan-2-one (306 mg, 3 mmol) and
phenylacetonitrile (352 mg, 3 mmol) in the yield of 63%. White solid,
ꢀ
[8]
m.p.: 93–94 C (lit. 102–102.5 C). Anal. Found: H 7.02, C 77.23;
ꢀ
1
C H NO requires C H O , H 6.98, C 77.2. H NMR (CDCl ) ꢁ :
1
3
15
13 14
2
3
H
1
.53 (6H, s, 2 Â CH ), 2.13 (3H, s, CH ), 7.36–7.46 (5H, m, Harom).
3
3
1
3
C NMR (CDCl ) ꢁ : 11.96 (C¼C–CH ), 24.72 (2 Â CH ), 85.38 (C ),
3
C
3
3
5
125.62 (C ), 128.26 (C
3
), 128.36 (C
), 128.93 (C
), 130.16
arom4
arom2,6
arom3,5
À1
cm : 3462, 2978,
max
(
Carom1), 165.03 (C ), 171.51 (CO ). IR (KBr) ꢀ
4
2
2
9
932, 1735 (ꢀ C¼O), 1666, 1494, 1434, 1386, 1294, 1224, 1166, 1080,
þ.
84, 910, 794, 756, 702. MS EI m/z (%): 203 (8.1), 202 (M , 50.8), 187
(
(
14.3), 175 (9.3), 160 (12.3), 159 (66.3), 131 (74.1), 115 (26.2), 91 (20.8), 77
13.7), 63 (10.6), 43 (100).
3-(4-Chloro-phenyl)-4,5,5-trimethyl-2-(5H )-furanone (4b): This pro-
duct was obtained from 3-hydroxy-3-methylbutan-2-one (306 mg,
3
of 63%. White solid, m.p.: 114.5–116 C, Anal. Found: H 5.49, C 65.85;
mmol) and (4-chlorophenyl)acetonitrile (455 mg, 3 mmol) in the yield
ꢀ
1
requires C H ClO , H 5.54, C 65.97. H NMR (CDCl ) ꢁ : 1.53 (6H, s,
1
3
13
2
3
H
3
2
 CH ), 2.12 (3H, s, CH ), 7.40 (2H, d, J ¼ 8.9 Hz, Harom), 7.44 (2H,
HH arom 3 C 3
3
3
13
HH
3
d, J ¼ 8.9 Hz, H
). C NMR (CDCl ) ꢁ : 12.00 (C¼C–CH ), 24.63
(
2 Â CH ), 85.50 (C ), 125.69 (C ), 128.58 (C
), 130.24 (C
arom3,5
),
3
5
3
arom2,6
134.24 (C
), 165.49 (C
), 171.16 (C ), 177.05 (CO). IR (KBr) ꢀ
arom4 4 max
arom1
À1
cm : 2984, 1744 (C¼O, lactone), 1670, 1592, 1492, 1460, 1436, 1392,
1
368, 1294, 1220, 1164, 1084, 982, 848, 828. MS EI m/z (%): 238
3
7
þ. þ.
ClO2 , 12.6), 236 (M , 38.6), 223 (4.1), 221 (11.3), 195
13
(
C H
1
3

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Application of Microwaves in Organic Synthesis
1583
(
4
14.9), 193 (43.1), 167 (14.5), 165 (44.2), 130 (18.7), 125 (7.0), 115 (15.6),
3 (100).
-(4-Chloro-phenyl)-5-ethyl-4,5-dimethyl-2-(5H )-furanone (4c): This
product was obtained from 3-hydroxy-3-methyl-pentan-2-one (348 mg,
3
3
White solid, m.p.: 57–58 C. Anal. Found:
mmol) and (4-chlorophenyl)acetonitrile in the yield of 67%.
ꢀ
H 5.60, C 66.01,
requires C H ClO , H 5.54, C 65.97. H NMR (CDCl ) ꢁ : 0.83
1
1
4
15
2
3
H
3
(
(
3H, t, JHH ¼ 7.4 Hz, CH CH ), 1.50 (3H, s, C¼C–CH ), 1.76
2
3
3
3
2
1H, td, JHH ¼ 7.4 Hz,
J
¼ 14.8 Hz, CH H CH ), 1.98 (1H, td,
HH
a
b
3
3
2
JHH ¼ 7.4 Hz,
J
¼ 14.8 Hz, CH H CH ), 2.07 (3H, s, CH ), 7.39
HH
a
b
3
3
3
3
(2H, d,
1
J
¼ 9.1 Hz, H
), 7.43 (2H, d,
J
¼ 9.1 Hz, H
).
arom
HH
arom
HH
3
C NMR (CDCl ) ꢁ : 7.28 (CH CH ), 12.10 (C¼C–CH ), 23.36
3
C
2
3
3
(
1
(
1
CH ), 30.00 (CH CH ), 87.86 (C ), 125.84 (C ), 128.58 (C
),
arom2,6
30.06 (Carom4), 130.23 (Carom3,5), 134.24 (Carom4), 164.21 (C ), 171.50
3
2
3
5
3
4
À1
CO). IR (KBr) ꢀmax cm : 2978, 2932, 2878, 1740 (C¼O, lactone),
666, 1594, 1492, 1456, 1378, 1312, 1214, 1090, 982, 924, 838. MS EI
ClO2 , 5.1), 250 (M , 15.8), 235 (1.4), 223 (14.8),
3
7
þ. þ.
m/z (%): 252 (C H
15
1
4
2
1
21 (41.9), 209 (2.4), 207 (7.5), 195 (2.7), 1193 (7.0), 181 (3.0), 179 (8.9),
67 (1.8), 165 (5.2), 128 (7.33), 115 (12.0), 57 (10.5), 43 (100).
3-(4-Methoxy-phenyl)-4,5,5-trimethyl-2-(5H )-furanone (4d): This
product was obtained from 3-hydroxy-3-methyl-butan-2-one (306 mg,
3
yield of 60%. White solid, m.p.: 85–86 C (lit.
mmol) and (4-methoxyphenyl)acetonitrile (442 mg, 3 mmol) in the
ꢀ
1
Found: H 6.95, C 72.42; requires C H O , H 6.94, C 72.39. H NMR
[16b]
ꢀ
52–53 C). Anal.
1
4
16
3
(
6
1
CDCl ) ꢁ : 1.51 (6H, s, 2 Â CH ), 2.11 (3H, s, CH ), 3.83 (3H, s, OCH ),
3
H
3
3
3
3
3
.96 (2H, d, J ¼ 8.8 Hz, H
), 7.44 (2H, d, J ¼ 8.8 Hz, H
).
arom
HH
arom
HH
3
C NMR (CDCl ) ꢁ : 11.93 (C¼C–CH ), 24.66 (2 Â CH ), 55.18
3
C
3
3
(
OCH ), 85.17 (C ), 113.77 (C
), 122.48 (C ), 124.86 (C
),
30.13 (Carom3,5), 159.41 (Carom4), 163.62 (C ), 171.75 (CO). IR (KBr)
3
5
arom2,6
3
arom1
1
4
À1
ꢀmax cm : 2980, 2958, 2934, 2838, 1730 (C¼O, lactone), 1660, 1608,
1
9
572, 1512, 1462, 1440, 1382, 1290, 1252, 1226, 1164, 1086, 1030, 984,
12, 838. MS EI m/z (%): 232 (M , 87.1), 217 (25.8), 189 (20.7), 161
þ.
(
(
100), 147 (23.5), 131 (7.2), 121 (4.2), 115 (8.8), 103 (6.6), 91 (6.3), 77
12.3), 43 (93.6).
3
-(3,4-Dimethoxy-phenyl)-4,5,5-trimethyl-2-(5H )-furanone (4e): This
product was obtained from 3-hydroxy-3-methyl-butan-2-one (306 mg,
3
yield of 67%. White solid, m.p.: 140–141 C. Anal. Found: H 6.94, C
mmol) and (3,4-dimethoxyphenyl)acetonitrile (532 mg, 3 mmol) in the
ꢀ
1
6
8.62; C H O requires H 6.92, C 68.69. H NMR (CDCl ) ꢁ : 1.51
15 18 4 3 H
(
6H, s, 2 Â CH ), 2.12 (3H, s, CH ), 3.89 (3H, s, OCH ), 3.90 (3H, s,
3
3
3
3
3
OCH ), 6.91 (1H, d, J ¼ 8.3 Hz, H
0
), 7.00 (1H, dd, J ¼ 8.3 Hz,
HH
3
HH
arom2
4
3
4
JHH ¼ 1.8 Hz, Harom 6 ), 7.07 (1H, dd, JHH ¼ 8.3 Hz, JHH ¼ 1.8 Hz,
0

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1
584Villemin and Liao
1
3
Harom5
0
). C NMR (CDCl ) ꢁ : 11.97 (C¼C–CH ), 24.65 (2 Â CH ),
3
C
3
3
5
1
1
5.79 (OCH ), 55.83 (OCH ), 85.14 (C ), 110.89 (C ), 112.03,
3
3
5
arom2,6
21.65, 122.79, 124.99, 148.67 (C
71.62 (C¼O). IR (KBr) ꢀ
0
), 148.99 (Carom4
0
), 163.84 (C4),
cm : 2984, 2958, 2934, 2836, 1733
arom3
À1
max
(
C¼O, lactone), 1658, 1600, 1578, 1516, 1468, 1442, 1380, 1326, 1300,
1258, 1240, 1210, 1156, 1140, 1090, 1024, 968, 920, 868, 824, 762. MS EI
m/z (%): 262 (M , 85.1), 247 (21.6), 224 (5.4), 219 (5.6), 191 (100), 177
þ.
(
7
32.1), 162 (12.3), 160 (9.3), 151 (5.6), 145 (4.9), 115 (6.1), 107 (7.6),
7 (16.9), 65 (14.5), 51 (28.7), 49 (56.4), 43 (65.7).
-Methyl-3-phenyl-1-oxa-spiro[4.5]dec-3-en-2-one (4f ): This product
4
was obtained from 1-(1-hydroxy-cyclohexyl)ethanone (348 mg, 3 mmol),
and phenylacetonitrile (3 mmol, 352 mg) in the yield of 63%. Pale yellow
ꢀ
[8]
solid, m.p.: 131–132 C (lit. 136–136.5 C). Anal. Found: H 7.56, C 79.37,
ꢀ
1
requires C H O , H 7.49, C 79.31. H NMR (CDCl ) ꢁ : 1.15–1.30 (2H,
1
6
18
2
3
H
m, CH ), 1.50–1.62 (2H, m, CH ), 1.65–1.90 (6H, m, 3 Â CH ), 2.10 (3H,
2
2
2
1
3
s, CH ), 7.28–7.50 (5H, m, H
3
). C NMR (CDCl ) ꢁ : 12.25
3 C
arom
(
1
C¼C–CH ), 21.90 (2 Â CH ), 24.56 (CH ), 33.41 (2 Â CH ), 87.00 (C ),
3
2
2
2
5
25.69 (C ), 128.14 (C ), 128.30 (C
arom2,6
Carom1), 165.37 (C ), 171.86 (CO). IR (KBr) ꢀ
), 128.94 (C
), 130.24
arom3,5
3
arom4
À1
(
(
5
cm : 2934, 2864, 1734
4
max
C¼O, lactone), 1662, 1492, 1444, 1382, 1204, 1122, 984, 944, 860, 794,
þ.
80. MS EI m/z (%): 242 (M , 66.7), 227 (5.1), 199 (100), 186 (45.1), 171
(
7
46.2), 158 (13.3), 143 (27.5), 129 (30.0), 115 (59.2), 105 (4.2), 91 (14.2),
7 (9.9), 65 (8.8), 55 (38.9), 43 (14.3).
ACKNOWLEDGMENTS
´
gion Basse et Haute-Normandie (Rincof )’’ for their
We thank the ‘‘re
generous financial support(grantfor L. L.).
REFERENCES
1. For reviews on 2(5H )-furanones(but-2-en-4-olides) see: (a) Rao, Y.S.
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(
(
c) Avetisyan A.A.; Dangyan, M.T. Russ. Chem. Rev. 1977, 46, 643;
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2
1990, 53, 237; (b) Fang, X.; Rieser, M.J.; Gu, Z.M.; McLaughlin,
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Application of Microwaves in Organic Synthesis
1585
Oberlies, N.H.; Zeng, L.; McLaughlin, J.L. In Recent Advances in
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9
1
`
´
10. For a review on focused microwave action: Loupy, A.; Petit, A.;
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1
1
1
1
[
13]
2. The synthesis of lactam in these conditions was described,
whatever the conditions we have obtain only iminolactone.
but
3. Melikian, G.; Rouessac, F.; Alexandre, C. Synth. Commun. 1993,
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4. (a) Vogel, P. Chimie Organique; DeBoech Universite
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2
´
: Bruxelles,
(
1
1
1
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