Green, microwave-assisted approach to the synthesis of arylidene- substituted spiro[4,5]decan-8-one derivatives in water

Article abstract of DOI:10.1080/00397910903009471

A green approach to the synthesis of arylidene-substituted spiro[4,5]decan-8-one derivatives was successfully realized via the mild, base-catalyzed reaction of aromatic aldehydes with 1,4-dioxa-spiro[4.5]decan-8- one in water under microwave irradiation. This protocol has the prominent advantages of environmental friendliness, short reaction time, excellent yields, low cost, easy operation, and broad scope of applicability. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910903009471

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Green, Microwave-Assisted Approach to
the Synthesis of Arylidene-Substituted
Spiro[4,5]decan-8-one Derivatives in
Water
Ju-Hua Peng a , Xiao-Hong Zhang b , Feng Shi b , Wen-Juan Hao b &
Shu-Jiang Tu a
a Lianyungang Teachers' College , Lianyungang, Jiangsu, China
b School of Chemistry and Chemical Engineering, Xuzhou Normal
University , Xuzhou, Jiangsu, China
Published online: 03 Feb 2010.
To cite this article: Ju-Hua Peng , Xiao-Hong Zhang , Feng Shi , Wen-Juan Hao & Shu-Jiang Tu (2010)
Green, Microwave-Assisted Approach to the Synthesis of Arylidene-Substituted Spiro[4,5]decan-8-one
Derivatives in Water, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 40:4, 615-623, DOI: 10.1080/00397910903009471
To link to this article: http://dx.doi.org/10.1080/00397910903009471
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Synthetic Communications1, 40: 615–623, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903009471
GREEN, MICROWAVE-ASSISTED APPROACH TO THE
SYNTHESIS OF ARYLIDENE-SUBSTITUTED
SPIRO[4,5]DECAN-8-ONE DERIVATIVES IN WATER
Ju-Hua Peng,1 Xiao-Hong Zhang,2 Feng Shi,2
Wen-Juan Hao,2 and Shu-Jiang Tu1
1Lianyungang Teachers’ College, Lianyungang, Jiangsu, China
2School of Chemistry and Chemical Engineering, Xuzhou Normal University,
Xuzhou, Jiangsu, China
A green approach to the synthesis of arylidene-substituted spiro[4,5]decan-8-one deriva-
tives was successfully realized via the mild, base-catalyzed reaction of aromatic aldehydes
with 1,4-dioxa-spiro[4.5]decan-8-one in water under microwave irradiation. This protocol
has the prominent advantages of environmental friendliness, short reaction time, excellent
yields, low cost, easy operation, and broad scope of applicability.
Keywords: Green synthesis; microwave irradiation; water
INTRODUCTION
The a,b-unsaturated derivatives of cyclohexanone attract great interest prim-
arily as intermediates. Because of the presence of its cross-conjugated dienone sys-
[3–9]
tem, it can react with many nucleophilic reagents such as urea,[1,2] thiourea,
cyanoacetamide,[3,9,10] and malononitrile.[11,12] The reactions of various mono- and
dienones based on cyclic ketones with aromatic aldehydes were studied.[13,14] Among
them, 2,6-bis(phenylmethylene)cyclohexanones have received considerable attention
over the past years because of their wide range of biological activities, such as cyto-
toxicity,[15] antimycotic,[16] antitumor,[17] antibacterial,[18] anti-inflammatory,[19] and
antileishmaniatic activities.[20] Therefore, chemists have made many efforts to syn-
thesize these compounds. For example, Jonathan and coworkers[21] have reported
the preparation of arylidene-substituted spiro[4,5]decan-8-one derivatives by
treatment of aromatic aldehydes with 1,4-dioxa-spiro[4,5]decan-8-one in ethanol
using sodium hydroxide as catalyst. First, the reactants were mixed at a low tempera-
ture (0–5ꢀC); then the mixture was performed under reflux for 24 h at room tempera-
ture. However, this method has many disadvantages such as long reaction time,
moderate yields, and fussy operation. It is worth mentioning that this method is
not a green one because corrosive catalyst and flammable solvent were used. Thus,
Received March 25, 2009.
Address correspondence to Shu-Jiang Tu, School of Chemistry and Chemical Engineering, Xuzhou
Normal University, Xuzhou, Jiangsu 221116, China. E-mail: laotu2001@263.net
615

616
J. H. PENG ET AL.
Scheme 1.
the development of a green and facile approach to arylidene-substituted
spiro[4,5]decan-8-one derivatives is still desired.
In past decades, microwave-assisted organic synthesis in water has become a
hotspot because it combines the two prominent green chemistry principles of ‘‘safer
solvents’’ and ‘‘energy efficiency.’’[22] Besides the general advantages of water and
microwave irradiation (MWI),[23] several important benefits are expected when they
are combined.[24] Water has become an attractive medium for many organic reac-
tions, not only because the need for drying reactants, expensive catalysts, and sol-
vents can be circumvented but also for its unique reactivity and selectivity.[25,26]
Many important types of heterocyclic compounds, such as triazines,[27] acridines,[28]
quinolines,[29] pyridines,[30] indoles,[31] pyrazines,[32] furans,[33] and pyrimidines,[34]
have been synthesized in aqueous media. Synthesis of new and important types of
heterocyclic compounds in water continues. The continued development of new reac-
tion processes in water to create new and important types of heterocyclic compounds
is becoming an interesting area. Herein, we report a green and facile approach
to the synthesis of arylidene-substituted spiro[4,5]decan-8-one derivatives 3
via microwave-assisted reactions of aromatic aldehyde 1 with 1,4-dioxa-spiro[4,5]-
decan-8-one 2 in water (Scheme 1) using potassium carbonate (K2CO3) as mild
catalyst.
RESULTS AND DISCUSSION
Choosing an appropriate solvent is of crucial importance for a successful
organic synthesis. To search for the optimal solvent, the microwave-assisted reaction
between 4-bromobenzaldehyde (1a) and 1,4-dioxa-spiro[4,5]decan-8-one (2) was
examined using potassium carbonate as mild catalyst in different solvents at
100ꢀC, including water, ethylene glycol, N,N-dimethylformamide (DMF), and etha-
nol. All the reactions were carried out at the maximum power of 200 W; the results
are summarized in Table 1. As can be seen from Table 1, reactions in glycol and
water gave better yields than others (Table 1, entries 1–4). Considering environmen-
tal friendliness and avoidance of toxic organic reagents, water thus was chosen as the
best solvent.
To further optimize the reaction conditions, the same reaction was performed
in water at temperatures ranging from 90 to 130ꢀC, with an increment of 10ꢀC each
time. The yield of product 3a was increased and the reaction time was shortened as
the temperature increased from 90ꢀC to 120ꢀC (Table 1, entries 5–7). However, the

SPIRO[4,5]DECAN-8-ONES
617
Table 1. Reaction conditions for the synthesis of 3a
Entry
Solvent
T (ꢀC)
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
glycol
DMF
EtOH
H2O
100
100
100
100
90
10
10
10
10
10
8
80
55
60
80
72
88
95
94
H2O
H2O
110
120
130
H2O
H2O
8
8
yield leveled off as the temperature increased from 120 to 130ꢀC (Table 1, entries 7
and 8). Thus, 120ꢀC was chosen as the optimal temperature for further reactions.
Furthermore, we were excited to find that only 0.4 equivalent of the catalyst gave
the best yield of product 3a at 120ꢀC.
The volume of water was also investigated. Different volumes of water were
tested at 120ꢀC for 8 min under MWI. When 1.5 mL water was used as solvent,
the yield was the great.
Under these optimized reaction conditions (1.5 mL water, 120ꢀC), different
aromatic aldehydes were employed in the reactions, and a series of arylidene-
substituted spiro[4,5]decan-8-ones 3 was synthesized. The results are summarized
in Table 2. As illustrated in Table 2, this protocol can be applied not only to the aro-
matic aldehydes with either electron-withdrawing groups (such as halide groups) or
electron-donating groups (such as alkoxyl group) but also to heterocyclic aldehydes.
Thus, the electronic nature of the substituents on aldehydes has no significant effect
on this reaction.
Compared with the method reported by Jonathan and coworkers, the use of
MWI has some obvious advantages. Take 3c as an example; the reaction time was
shortened strikingly from 12 h to 8 min, and the yield was increased from 67% to
95%. The difference may be a consequence of both thermal effects and specific effects
Table 2. Synthesis of 3 under microwave irradiation
Entry
3
Aromatic aldehydes (1)
Time (min) Yield (%)
Mp (ꢀC)
221–222
1
2
3a 1a 4-Bromobenzaldehyd
8
8
95
94
95
95
95
92
94
93
93
92
92
92
3b 1b 2-Chlorobenzaldehyde
3c 1c 4-Chlorobenzaldehyde
3d 1d 4-Fluorobenzaldehyde
3e 1e 2,4-Dichlorobenzaldehyde
3f 1f 3-Nitrobenzaldehyde
210–212
3
8
238–240 (210–212)[22]
225–227 (208–210)[22]
175–177
4
8
5
8
6
8
199–201
7
3g 1g 4-Methylbenzaldehyde
3h 1h 4-Methoxybenzaldehyde
3i 1i 3,4,5-Trimethoxybenzaldehyde
3j 1j 4-Dimethylaminobenzaldehyde
3k 1k Benzo[d][1,3]dioxole-5-carbaldehyde
3 l 1l Thiophene-2-carbaldehyde
9
257–258 (238–240)[22]
241–243 (224–226)[22]
178–180 (162–164)[22]
8
10
10
10
9
9
10
11
12
>300
287–289
197–199
9

618
J. H. PENG ET AL.
induced by the microwave field. The reactants in these multicomponent reactions
contain dipoles and proceed via related polar intermediates, which enhance their
interactions with microwave heating.
The structures of all the synthesized compounds were established on the basis
of spectroscopic data and high-resolution mass spectral (HRMS) data.
CONCLUSION
In brief, a green and facile approach to the synthesis of arylidene-substituted
spiro[4,5]decan-8-ones using potassium carbonate (K2CO3) as mild catalyst was
reported. This protocol has the prominent advantages of environmental friendliness,
short reaction time, excellent yields, low cost, broad scope of applicability, and mild
reaction condition. At the same time, this efficient synthesis cannot only offer a green
synthetic strategy to heterocyclic compounds but also enriches the investigations on
microwave-assisted reactions in water.
EXPERIMENTAL
MWI was carried out in a monomodal Emrys Creator from Personal Chemis-
try, Uppsala, Sweden. Melting points were determined on an XT5 apparatus and are
uncorrected. Infrared (IR) spectra were recorded on an Fourier transform (FT)-IR
1
Tensor 27 spectrometer. H NMR and 13C NMR were measured on a DPX 400
spectrometer operating at 400 MHz and 100 MHz, respectively using dimethylsulfox-
ide (DMSO-d6) as solvent and tetramethylsilane (TMS) as an internal standard.
HRMS (ESI) was determined by MicroTOF-Qll; HRMS=MS instrument (Bruker).
General Procedure for the Synthesis of Compounds 3 Under
Microwave Irradiation
Typically, in
a 10-mL Emrys reaction vial, aldehyde 1 (2 mmol),
1,4-dioxa-spiro[4,5]decan-8-one 2 (1 mmol), K2CO3 (0.4 mmol), and water (1.5 mL)
were mixed and then capped. The mixture was irradiated at 120ꢀC for a given time
(maximum power of 200 W). Upon completion, as monitored by thin-layer chroma-
tography (TLC), the reaction mixture was cooled to room temperature and filtered
to give the crude product, which was subsequently recrystallized from EtOH (95%)
to give the pure products 3.
Data
7,9-Bis-[1-(4-bromo-phenyl)-meth-(E)-ylidene]-1,4-dioxa-spiro[4,5]decan-
8-one (3a). IR (KBr, n, cmꢁ1): 2962, 2894, 1668, 1604, 1574, 1485, 1399, 1261, 1234,
1124, 1009, 987, 826, 760. 1H NMR (400 MHz, DMSO-d6) (d, ppm): 7.66
=
(t, J ¼ 7.8 Hz, 6H, CH and ArH), 7.49 (d, J ¼ 8.4 Hz, 4H, ArH), 3.82 (s, 4H,
CH2), 3.10 (s, 4H, CH2). 13C NMR (100 MHz, DMSO-d6) (d, ppm): 172.88,
152.06, 136.13, 134.07, 133.67, 132.22, 132.13, 131.61, 131.58, 131.41, 130.74,
105.92, 64.26, 37.15. HRMS (ESI) m=z: calc. for C22H18Br2O3: 510.9525 [M þ Na]þ;
found: 510.9532.

SPIRO[4,5]DECAN-8-ONES
619
7,9-Bis-[1-(2-chloro-phenyl)-meth-(E)-ylidene]-1,4-dioxa-spiro[4.5]decan-
8-one (3b). IR (KBr, n, cmꢁ1): 2902, 1674, 1616, 1562, 1421, 1273, 1192, 1040, 950,
1
=
763, 688. H NMR (400 MHz, DMSO-d6) (d, ppm): 7.81 (s, 2H, CH), 7.60–7.51 (m,
4H, ArH), 7.47–7.44 (m, 4H, ArH), 3.79 (s, 4H, CH2), 3.03 (s, 4H, CH2). 13C NMR
(100 MHz, DMSO-d6) (d, ppm): 186.93, 151.24, 134.69, 134.08, 133.87, 132.90,
130.68, 130.64, 129.70, 127.22, 114.87, 106.02, 64.23, 36.87. HRMS (ESI) m=z: calc.
for C22H18Cl2O3: 423.0526 [M þ Na]þ; found: 423.0512.
7,9-Bis-[1-(4-chloro-phenyl)-meth-(E)-ylidene]-1,4-dioxa-spiro[4,5]decan-
8-one (3c). IR (KBr, n, cmꢁ1): 2989, 2887, 1671, 1606, 1577, 1488, 1237, 1184, 1119,
1011, 951, 825. 1H NMR (400 MHz, DMSO-d6) (d, ppm): 7.66 (s, 2H, CH),
7.58–7.51 (m, 8H, ArH), 3.82 (s, 4H, CH2), 3.11 (s, 4H, CH2). HRMS (ESI) m=z:
=
calc. for C22H18Cl2O3: 401.0706 [M þ H]þ; found: 401.0692.
7,9-Bis-[1-(4-fluoro-phenyl)-meth-(E)-ylidene]-1,4-dioxa-spiro[4,5]decan-
8-one (3d). IR (KBr, n, cmꢁ1): 2906, 1673, 1609, 1599, 1507, 1411, 1222, 1160,
1045, 984, 836. 1H NMR (400 MHz, DMSO-d6) (d, ppm): 7.68 (s, 2H, CH),
=
7.63–7.59 (m., 4H, ArH), 7.30 (t, J ¼ 8.8 Hz, 4H, ArH), 3.82 (s, 4H, CH2), 3.11 (s,
4H, CH2). 13C NMR (100 MHz, DMSO-d6) (d, ppm): 187.18, 163.42, 160.96,
136.20, 132.76, 132.63, 132.55, 131.44, 131.41, 115.76, 115.55, 106.00, 64.22, 37.11.
HRMS (ESI) m=z: calc. for C22H18F2O3: 391.1117 [M þ Na]þ; found: 391.1106.
7,9-Bis-[1-(2,4-dichloro-phenyl)-meth-(E)-ylidene]-1,4-dioxa-spiro[4,5]-
decan-8-one (3e). IR (KBr, n, cmꢁ1): 2949, 1676, 1611, 1584, 1467, 1265, 1103,
1
=
1045, 986, 844, 775. H NMR (400 MHz, DMSO-d6) (d, ppm): 7.78 (s, 2H, CH),
7.75 (d, J ¼ 7.2 Hz, 2H, ArH), 7.57–7.51 (m., 4H, ArH), 3.79 (s, 4H, CH2), 3.01 (s,
4H, CH2). 13C NMR (100 MHz, DMSO-d6) (d, ppm): 185.93, 160.33, 142.58,
137.97, 132.09, 124.20, 123.35, 122.22, 121.32, 106.82, 70.58, 48.58, 36.03. HRMS
(ESI) m=z: calc. for C22H16Cl4O3: 468.9927 [M þ Na]þ; found: 468.9932.
7,9-Bis-[1-(3-nitro-phenyl)-meth-(E)-ylidene]-1,4-dioxa-spiro[4,5]decan-
8-one (3f). IR (KBr, n, cmꢁ1): 2897, 1673, 1614, 1528, 1351, 1196, 1101, 1040, 948,
1
=
817, 680. H NMR (400 MHz, DMSO-d6) (d, ppm): 8.34 (s, 2H, CH), 8.27–8.24 (m,
2H, ArH), 8.00 (d, J ¼ 8.0, 2H, ArH), 7.79–7.75 (m, 4H, ArH), 3.83 (s, 4H, CH2),
3.19 (s, 4H, CH2). 13C NMR (100 MHz, DMSO-d6) (d, ppm): 187.03, 147.93,
136.39, 136.33, 135.23, 135.14, 130.16, 124.35, 123.46, 105.86, 64.33, 36.99. HRMS
(ESI) m=z: calc. for C22H18N2O7: 445.1012 [M þ Na]þ; found: 445.1012.
7,9-Bis-[1-p-tolyl-meth-(E)-ylidene]-1,4-dioxa-spiro[4,5]decan-8-one (3g).
1
IR (KBr, n, cmꢁ1): 2891, 1671, 1605, 1578,1508, 1263, 1178, 1120, 988, 814. H
=
NMR (400 MHz, DMSO-d6) (d, ppm): 7.65 (s, 2H, CH), 7.43 (d, J ¼ 8.0 Hz, 4H,
ArH), 7.28 (d, J ¼ 8.0 Hz, 4H, ArH), 3.81 (s, 4H, CH2), 3.12 (s, 4H, CH2), 2.35
(s, 6H, CH3). HRMS (ESI) m=z: calc. for C24H24O3: 383.1618 [M þ Na]þ; found:
383.1616.
7,9-Bis-[1-(4-methoxy-phenyl)-meth-(E)-ylidene]-1,4-dioxa-spiro[4,5]decan-
8-one (3h). IR (KBr, n, cmꢁ1): 2962, 1673, 1602, 1509, 1461, 1251, 1168, 1025, 984,
1
=
834, 531 cm. H NMR (400 MHz, DMSO-d6) (d, ppm): 7.65 (s, 2H, CH), 7.51
(d, J ¼ 8.8 Hz, 4H, ArH), 7.03 (d, J ¼ 8.8 Hz, 4H, ArH), 3.80 (t, J ¼ 9.2 Hz, 10H,
CH2 and OCH3), 3.11 (s, 4H, CH2). 13C NMR (100 MHz, DMSO-d6) (d, ppm):

620
J. H. PENG ET AL.
186.63, 159.88, 136.99, 132.18, 132.11, 130.91, 127.50, 114.19, 106.16, 64.21, 55.28,
37.31. HRMS (ESI) m=z: calc. for C24H24O5: 415.1516 [M þ Na]þ; found: 415.1511.
7,9-Bis-[1-(3,4,5-methoxy-phenyl)-meth-(E)-ylidene]-1,4-dioxa-spiro[4,5]
decan-8-one (3i). IR (KBr, n, cmꢁ1): 2887, 1657, 1615, 1590, 1523, 1421, 1372,
1272, 1169, 985, 813. 1H NMR (400 MHz, DMSO-d6) (d, ppm): 7.65 (s, 2H,
=
CH), 6.84 (s, 4H, ArH), 3.84 (d, J ¼ 13.2 Hz, 16H, CH2 and OCH3), 3.71 (s, 6H,
OCH3), 3.17 (s, 4H, CH2). 13C NMR (100 MHz, DMSO-d6) (d, ppm): 187.20,
152.74, 152.05, 138.38, 137.60, 132.32, 130.45, 130.26, 107.93, 106.04, 64.22, 60.11,
56.03, 37.10. HRMS (ESI) m=z: calc. for C28H30O9: 535.1939 [M þ Na]þ; found:
535.1923.
7,9-Bis-[1-(4-dimethylamino-phenyl)-meth-(E)-ylidene]-1,4-dioxa-spiro[4,5]
decan-8-one (3j). IR (KBr, n, cmꢁ1): 2942, 2889, 1657, 1589, 1524, 1421, 1372,
1272, 1179, 1119, 984, 813. 1H NMR (400 MHz, DMSO-d6) (d, ppm): 7.69
=
=
(d, J ¼ 8.0 Hz, 1H, CH), 7.59 (s, 1H, CH), 7.41–7.35 (m, 4H, ArH), 6.81–6.74
(m, 4H, ArH), 3.91 (d, J ¼ 4.0 Hz, 2H, CH2), 3.84 (s, 2H, CH2), 3.07 (d, J ¼ 12.0 Hz,
Hz, 4H, CH2), 2.98 (s, 12H, NCH3). HRMS (ESI) m=z: calc. for C26H30N2O3:
419.2335 [M þ H]þ; found: 419.2329.
7,9-Bis-[1-benzo[1,3]dioxol-5-yl-meth-(E)-ylidene]-1,4-dioxa-spiro[4,5]
decan-8-one (3k). IR (KBr, n, cmꢁ1): 2889, 1664, 1594, 1490, 1446, 1222, 1121,
1099, 1032, 912, 815. 1H NMR (400 MHz, DMSO-d6) (d, ppm): 7.60 (s, 2H,
=
CH), 7.13–7.01 (m, 6H, ArH), 6.10 (s, 4H, CH2), 3.83 (s, 4H, CH2), 3.09 (s, 4H,
CH2). 13C NMR (100 MHz, DMSO-d6) (d, ppm): 185.07, 162.27, 135.25, 134.86,
134.29, 133.01, 131.90, 131.86, 129.28, 127.48, 122.35, 105.90, 86.23, 64.26, 36.84.
HRMS (ESI) m=z: calc. for C24H20O7: 443.1102 [M þ Na]þ; found: 443.1092.
7,9-Bis-[1-thiophen-2-yl-meth-(E)-ylidene]-1,4-dioxa-spiro[4,5]decan-8-
one (3l). IR (KBr, n, cmꢁ1): 3104, 2891, 1656, 1588, 1413, 1344, 1206, 1094, 947,
1
=
722, 559. H NMR (400 MHz, DMSO-d6) (d, ppm): 7.91 (t, J ¼ 4.0 Hz, 4H, CH
and ArH), 7.71–7.53 (m, 2H, ArH), 7.28–7.15 (m, 2H, ArH), 3.97 (d, J ¼ 6.8 Hz,
4H, CH2), 3.12 (s, 3H, CH2), 3.01 (d, J ¼ 15.6 Hz, 1H, CH2). 13C NMR
(100 MHz, DMSO-d6) (d, ppm): 186.06, 138.16, 134.15, 131.47, 130.20, 129.63,
128.19, 105.91, 64.44, 37.16. HRMS (ESI) m=z: calc. for C18H16O3S2: 367.0439
[M þ Na]þ; found: 367.0444.
ACKNOWLEDGMENTS
We thank the National Natural Science Foundation of China (Nos. 20672090
and 200810102050) and the Key Item program of the Natural Science Foundation of
Xuzhou Normal University (No. 07XLA04) for financial support.
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