Ultrasound mediation for efficient synthesis of monoarylidene derivatives of homo- and heterocyclic ketones

Article abstract of DOI:10.1016/j.ultsonch.2012.11.004

Ultrasonic irradiation was efficiently used for high yield synthesis of monoarylidene derivatives of cyclic systems directly from the reaction of ketone with various aldehydes under solvent-free conditions. Reactions took place rapidly in the presence of catalytic amounts of pyrrolidine, while no significant formation of the undesired bis by-products was observed. Moreover, the procedure was applicable to both homo- and heterocyclic ketones.

Full text of DOI:10.1016/j.ultsonch.2012.11.004

Accepted Manuscript
Ultrasound mediation for efficient synthesis of monoarylidene derivatives of
homo- and heterocyclic ketones
Mohammad M. Mojtahedi, M. Saeed Abaee, Mehdieh Samianifard, Akram
Shamloo, Masoomeh Padyab, A. Wahid Mesbah, Klaus Harms
PII:
S1350-4177(12)00250-7
DOI:
http://dx.doi.org/10.1016/j.ultsonch.2012.11.004
ULTSON 2223
Reference:
To appear in:
Ultrasonics Sonochemistry
Received Date:
Revised Date:
Accepted Date:
10 September 2012
5 November 2012
6 November 2012
Please cite this article as: M.M. Mojtahedi, M. Saeed Abaee, M. Samianifard, A. Shamloo, M. Padyab, A. Wahid
Mesbah, K. Harms, Ultrasound mediation for efficient synthesis of monoarylidene derivatives of homo- and
heterocyclic ketones, Ultrasonics Sonochemistry (2012), doi: http://dx.doi.org/10.1016/j.ultsonch.2012.11.004
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Ultrasound mediation for efficient synthesis of monoarylidene derivatives of
homo- and heterocyclic ketones
Mohammad M. Mojtahedi a,*, M. Saeed Abaee b,*, Mehdieh Samianifard b, Akram
Shamloo b, Masoomeh Padyab b, A. Wahid Mesbah b, Klaus Harms c
a Department of Chemistry, Saveh Branch, Islamic Azad University, Saveh, Iran
b Chemistry and Chemical Engineering Research Center of Iran, P.O.Box 14335-186
Tehran, Iran
c Fachbereich Chemie der Philipps-Universitaet Marburg, Hans-Meerwein-Strasse, D-
35032 Marburg, Germany
E-mail: mojtahedi@ccerci.ac.ir; E-mail: abaee@ccerci.ac.ir
Tel.: +98 21 44580749; Fax: +98 21 44580785
Abstract: Ultrasonic irradiation was efficiently used for high yield synthesis of
monoarylidene derivatives of cyclic systems directly from the reaction of ketone with
various aldehydes under solvent-free conditions. Reactions took place rapidly in the
presence of catalytic amounts of pyrrolidine, while no significant formation of the
undesired bis by-products was observed. Moreover, the procedure was applicable to
both homo- and heterocyclic ketones.
Keywords: ,-Unsaturated ketones; Ultrasonic irradiation; Heterocyclic synthesis;
Aldol condensation
1. Introduction
In recent decades, scientific and industrial activities have focused on designing
chemical methodologies and technologies which are more environmentally friendly
1

and can reduce chemical disposals and energy consumptions. In this regard, an
illustrative area of success involves the application of sonochemical irradiation in
various science and engineering disciplines [1-3]. In particular, this application in
synthetic chemistry has caused increased reactivity and selectivity in many organic
transformations [4]. This enhancement occurs either as a result of producing new
reacting species or is due to increased mechanical effects in the reaction mixtures [5].
Therefore, many new protocols are offered to conduct synthetic procedures in shorter
time intervals and under more environmentally friendly conditions [6].
Compounds possessing carbonyl groups conjugated with ,-unsaturated carbon–
carbon bonds are considered as vary important moieties in synthetic organic
chemistry since they are the key substructure of many naturally occurring and
biologically active molecules [7-9]. In addition, conjugated enone functionalities are
appropriate precursors for other synthetic transformations [10-11]. Synthesis of
conjugated enones is usually carried out using aldol condensation reactions [12], a
process which often requires the use of strong bases and suffers from undesired
double condensation reaction in the case of symmetrical ketones possessing two
groups of active methylenes. Like many other synthetic transformations, several
methods have been reported in recent years on ultrasound mediated aldol
condensation reactions [13-14]. However, the methods have been mainly limited to
the synthesis of chalcone [15-20] and bisarylidene [21] derivatives. To the best of our
knowledge, so far no one has studied sonochemical preparation of monoarylidenes of
cyclic ketones, an important group of ,-unsaturated ketones which have their own
synthetic and biological applications. For example these compounds have been
employed as precursors for the synthesis of various products such as chiral odorants
[22], phenol derivatives [23], and Baylis-Hillman adducts [24] or as fungicides for the
2

protection of agricultural products [25], antimycrobacterial agents [26], and
antiproliferative active compounds [27].
In the framework of our investigations on the synthesis of arylmethylidenes of
different cycloketones [28-31] and based on our previous experiences on the
development of green methodologies [32-34], we are encouraged to develop a
sonochemical procedure for controlled condensation of various cyclic ketones in the
presence of organocatalysts so that the formation of the bis by-products is minimized.
As a consequence of our studies, herein we report a novel and high yield
sonochemical method for the synthesis of monoarylidene derivatives. The procedure
is applicable to both homo- and heterocyclic ketones (Scheme 1).
Scheme 1.
2. Method
2.1. Apparatus and analysis
Reactions were monitored by TLC. FT-IR spectra were recorded using KBr disks on a
Bruker Vector-22 infrared spectrometer and absorptions were reported as wave
numbers (cm-1). NMR spectra were obtained on a FT-NMR Bruker Ultra ShieldTM
(500 MHz) instrument as CDCl3 solutions and the chemical shifts were expressed as 
units with Me4Si as the internal standard. Mass spectra were obtained on a Finnigan
Mat 8430 apparatus at ionization potential of 70 eV. All chemicals and reagents
were purchased from commercial sources and were purified by standard
procedures prior to use. Sonication was performed using a Sartorius Ultrasonic-
homogenizer LABSONICP 230V/50 Hz instrument with a frequency of 24 KHz
and nominal power of 460 W/cm2. The intensity level of irradiation was adjusted at
80% level for the synthesis of the products. In all reactions the tip of the sonotrode
3

was located in the same position just under the liquid surface in order to obtain
optimal sonication and reproducible results. The ultrasonic intensity and ultrasonic
density of the instrument were measured by a known calorimetric method [35] (for
the synthesis of 3a from cyclohexanone and benzaldehyde in the presence of
pyrrolidine) and were found to be equal to 5.14 W/cm2 and 0.25 W/cm3, respectively.
2.2. General procedure
A mixture of an aldehyde (3.00 mmol), a ketone (3.00 mmol), and pyrrolidine (107
mg, 123 l, 1.5 mmol) was sonicated under inert atmosphere for the given period of
time. The progress of the reaction was monitored by TLC using silica gel coated
plates and petroleum ether/EtOAc (4:1). At the end, water (5 mL) was added to the
mixture and the product was extracted with Et2O (2×5 mL). The organic layer was
dried over Na2SO4. Evaporation of the solvent led to a residue which was purified by
either column chromatography (using silica gel and petroleum ether/EtOAc (4:1) as
the eluent) or recrystallization from EtOAc. The identity of known compounds (3a-h
[36-38] and 5a [26,31]) was confirmed by the comparison of their spectral and
physical data with those available in the literature. The structure of new products was
determined by their physical and spectroscopic specifications and their purity was
confirmed by elemental analyses. In temperature controlled experiments, reactions
were performed in a water bath at 25±1 oC.
2.3. Selected spectral data
(E)-3-(Naphthalen-2-ylmethylene)dihydro-2H-pyran-4(3H)-one (4a). Yellow solid
was obtained in 72% yield. Mp 125-127 oC; 1H NMR (500 MHz, CDCl3) δ 2.70-2.73
(m, 2H), 4.09-4.11 (m, 2H), 4.97 (d, J = 2.0 Hz, 2H), 7.37 (dd, J = 1.5, 8.5 Hz, 1H),
7.49-7.55 (m, 2H), 7.73 (s, 1H), 7.78 (dd, J = 2.0, 2.0 Hz, 1H ), 7.82-7.85 (m, 1H)
13
ppm; C NMR (125 MHz, CDCl3) δ 40.2, 66.0, 69.3, 127.2, 127.8, 127.9, 128.1,
4

128.8, 129.0, 131.3, 132.3, 133.4, 133.7, 133.8, 136.6, 196.4 ppm; IR (neat)  1682,
1586, 1223 cm–1; MS (70 eV): m/z 238 (M+), 221, 181, 165, 153. Anal. Calcd for
C16H14O2: C, 80.65; H,5.92. Found. C, 80.30; H, 5.91.
(E)-3-(4-Methylbenzylidene)dihydro-2H-pyran-4(3H)-one (4b). White solid was
obtained in 71% yield. Mp 115-116 oC; 1H NMR (500 MHz, CDCl3) δ 2.37 (s, 3H),
2.66-2.68 (m, 2H), 4.06-4.08 (m, 2H), 4.85 (d, J = 2.0 Hz, 2H), 7.18 (d, J = 8.2 Hz,
2H), 7.23 (d, J = 8.2 Hz, 2H), 7.61 (s, 1H) ppm; 13C NMR (125 MHz, CDCl3) δ 21.9,
40.1, 65.9, 69.2, 129.9, 131.2, 132.0, 132.8, 136.6, 140.4, 196.5 ppm; IR (neat) 
2857, 1681, 1235 cm–1; MS (70 eV): m/z 202 (M+), 187, 131, 115. Anal. Calcd for
C13H14O2: C, 77.20, H, 6.98. Found: C 76.94; H, 7.05.
(E)-3-(3-Fluorobenzylidene)dihydro-2H-pyran-4(3H)-one (4c). White solid was
obtained in 77% yield. Mp 116-117 oC; 1H NMR (500 MHz, CDCl3) δ 2.68-2.70 (m,
2H), 4.06-4.09 (m, 2H), 4.82 (d, J = 1.0 Hz, 2H), 6.95 (d, J = 9.5 Hz, 1H), 7.04-7.09
13
(m, 2H), 7.36 (m, 1H), 7.55 (ap s, 1H) ppm; C NMR (125 MHz, CDCl3) δ 40.2,
65.9, 68.9, 116.7, 116.9, 117.3, 117.4, 126.7, 130.6, 130.7, 134.7, 134.9, 136.8, 196.3
ppm; IR (neat)  1682, 1577 cm–1; MS (70 eV): m/z 206 (M+), 149, 133, 121. Anal.
Calcd for C12H11FO2: C,69.89, H, 5.38. Found: C, 70.08; H, 5.69.
(E)-3-(4-Bromobenzylidene)dihydro-2H-pyran-4(3H)-one (4d). White solid was
obtained in 74% yield. Mp 119-120 oC; 1H NMR (500 MHz, CDCl3) δ 2.67-2.70 (m,
2H), 4.06-4.08 (m, 2H), 4.80 (d, J = 1.0 Hz, 2H), 7.13 (d, J = 8.5 Hz, 2H), 7.52 (d, J =
1.0 Hz, 1H), 7.54 (d, J = 8.5 Hz, 2H) ppm; 13C NMR (125 MHz, CDCl3) δ 40.2, 65.9,
69.0, 124.4, 132.3, 132.4, 133.6, 134.2, 135.1, 196.3 ppm; IR (neat)  1679, 1595 cm–
1; MS (70 eV): m/z 267 (M+), 212, 187, 131. Anal. Calcd for C12H11BrO2: C, 53.96,
H, 4.15. Found: C 54.38; H, 4.24.
5

(E)-3-Benzylidene-1-methylpiperidin-4-one (5a). An oil was obtained in 62% yield.
1H NMR (500 MHz, CDCl3) δ 2.33 (s, 3H), 2.55-2.58 (m, 2H), 2.68-2.71 (m, 2H),
3.56 (s, 2H), 7.23-7.25 (m, 3H), 7.28-7.31 (m, 2H), 7.49 (s, 1H) ppm; 13C NMR (125
MHz, CDCl3) δ 39.1, 46.2, 52.6, 57.6, 127.9, 129.1, 130.4, 132.9, 134.4, 135.7, 197.4
ppm.
(E)-1-Methyl-3-(3-methylbenzylidene)piperidin-4-one (5b). An oil was obtained in
1
65% yield. H NMR (500 MHz, CDCl3) δ 2.33 (s, 3H), 2.40 (s, 3H), 2.61-2.64 (m,
2H), 2.76-2.78 (m, 2H), 3.61 (d, Ј = 1.5 Hz, 2H), 7.10-7.13 (m, 3H), 7.25 (dd, Ј = 7.6,
8.0 Hz, 1H), 7.52 (d, Ј = 1.5 Hz, 1H) ppm; 13C NMR (125 MHz, CDCl3) δ 21.8, 39.5,
46.6, 53.2, 58.1, 127.8, 128.8, 130.3, 131.6, 133.2, 135.3, 136.5, 138.6, 198.1 ppm; IR
(neat)  1678, 1575 cm–1; MS (70 eV): m/z 215 (M+), 186, 158, 129. Anal. Calcd for
C14H17NO: C, 78.10, H, 7.96. Found: C 78.29; H, 8.12.
(E)-3-(4-Chlorobenzylidene)-1-methylpiperidin-4-one (5c). An yellow paste was
obtained in 70% yield. 1H NMR (500 MHz, CDCl3) δ 2.57 (s. 3H), 2.77-2.79 (m, 2H),
2.94-3.00 (m, 2H), 3.81 (d, Ј = 1.8 Hz, 2H), 7.25 (d, Ј = 8.5 Hz, 2H), 7.38 (d, Ј = 8.5
Hz, 2H), 7.58 (ap. s, 1H) ppm; 13C NMR (125 MHz, CDCl3) δ 39.4, 46.5, 53.0, 57,9,
129.2, 131.3, 132.0, 133.8, 134.8, 135.5, 194.7 ppm; IR (neat) 1726, 1687 cm–1; MS
(70 eV): m/z 235 (M+), 158, 114, 42. Anal Calcd for C13H14ClNO: C, 66.24; H, 5.99.
Found: C, 66.20, H, 5.90.
(E)-1-Methyl-3-(thiophen-2-ylmethylene)piperidin-4-one (5d). An oil was obtained
1
in 75% yield. H NMR (500 MHz, CDCl3) δ 2.51 (s, 3H), 2.64-2.66 (m, 2H), 2.80-
2.82 (m, 2H), 3.69 (d, Ј = 1.5 Hz, 2H), 7.14 (dd, Ј = 3.8, 5.0 Hz, 1H), 7.31 (d, Ј = 3.8
Hz, 1H), 7.50 (d, Ј = 5.0 Hz, 1H), 7.78 (d, Ј = 1.5 Hz 1H) ppm; 13C NMR (125 MHz,
CDCl3) δ 39.3, 46.7, 52.6, 58.1, 128.4, 128.9, 129.7, 131.3, 133.9, 138.6, 197.2 ppm;
6

IR (neat)  1687, 1601 cm–1; MS (70 eV): m/z 207 (M+), 206, 178, 150, 121. Anal.
Calcd for C11H13NOS: C, 63.74, H, 6.32. Found: C 63.38; H, 6.55.
(Z)-3-(2-Methylbenzylidene)dihydro-2H-thiopyran-4(3H)-one (6a). Yellow solid
was obtained in 70% yield. Mp 62-65 oC; 1H NMR (500 MHz, CDCl3) δ 2.88 (s, 3H),
2.88-2.91 (m, 2H), 2.99-3.02 (m, 2H), 3.65 (s, 2H), 7.12 (d, J = 7.5 Hz, 1H), 7.17-
7.25 (m, 3H), 7.56 (s, 1H) ppm; 13C NMR (125 MHz, CDCl3) δ 20.4, 26.5, 29.0, 42.0,
126.1, 129.2, 130.8, 134.4, 135.2, 135.4, 138.2, 199.3 ppm; IR (neat)  1728, 1673,
1594 cm–1; MS (70 eV): m/z 218 (M+), 203, 190, 149, 128. Anal. Calcd for
C13H14OS: C, 71.52, H, 6.46. Found: C 71.22; H, 6.86.
(Z)-3-(3,4,5-Trimethoxybenzylidene)dihydro-2H-thiopyran-4(3H)-one
(6b).
Cream colored solid was obtained in 68% yield. Mp 93-95 oC; 1H NMR (500 MHz,
CDCl3) δ 2.86-2.89 (m, 2H), 2.98-3.00 (m, 2H), 3.83 (s, 2H), 3.84 (s, 6H), 3.85 (s,
3H), 6.55 (s, 2H), 7.43 (s, 1H) ppm; 13C NMR (125 MHz, CDCl3) δ 26.2, 29.1, 41.6,
56.6, 61.3, 107.6, 130.6, 134.3, 136.4, 139.3, 153.6, 199.0 ppm; IR (neat)  1682,
1605, 1576 cm–1; MS (70 eV): m/z 294 (M+), 263, 205, 191, 60, 45. Anal. Calcd for
C15H18O4S: C, 61.20, H, 6.16. Found: C 61.23; H, 6.42.
(Z)-3-(2-Fluorobenzylidene)dihydro-2H-thiopyran-4(3H)-one (6c). Yellow solid
was obtained in 75% yield. Mp 43-45 oC; 1H NMR (500 MHz, CDCl3) δ 2.89-2.91 (m,
2H), 3.00-3.02 (m, 2H), 3.68 (s, 2H), 7.09 (dd, J = 9.0, 9.5 Hz, 1H), 7.15 (dd, J = 7.5,
13
7.5 Hz, 1H), 7.26 (dd, J = 7.0, 7.5 Hz, 1H), 7.35 (m, 1H), 7.47 (s, 1H) ppm; C
NMR (125 MHz, CDCl3) δ 26.6, 29.5, 42.0, 116.4 (d, J = 22.0 Hz), 123.1 (d, J = 14.0
Hz), 124.5 (d, J = 4.0 Hz), 128.9 (d, J = 2.5 Hz), 131.1 (d, J = 3.0 Hz), 131.2 (d, J =
8.0 Hz), 136.8, 160.9 (d, J = 249.0 Hz), 198.8 ppm; IR (neat)  1679, 1612, 1479 cm–
1; MS (70 eV): m/z 222 (M+), 165, 133, 107, 60, 45. Anal. Calcd for C12H11FOS: C,
64.84, H, 4.99. Found: C 64.56; H, 5.16.
7

(Z)-3-(3-Nitrobenzylidene)dihydro-2H-thiopyran-4(3H)-one (6d). Cream colored
solid was obtained in 65% yield. Mp 97-99 oC; 1H NMR (500 MHz, CDCl3) δ 2.92-
2.94 (m, 2H), 3.03-3.05 (m, 2H), 3.77 (s, 2H), 7.46 (s, 1H), 7.58-7.65 (m, 2H), 8.17
13
(s, 1H), 8.19 (d, J = 8.0 Hz, 1H) ppm; C NMR (125 MHz, CDCl3) δ 26.5, 29.0,
41.9, 123.9, 124.6, 130.2, 132.8, 135.9, 136.8, 137.2, 148.8, 198.7 ppm; IR (neat) 
1691, 1613, 1529 cm–1; MS (70 eV): m/z 249 (M+), 232, 193, 176, 146, 115. Anal.
Calcd for C12H11NO3S: C, 57.82, H, 4.45. Found: C 57.78; H, 4.53.
2.4. X-ray crystal structure analysis of 4a
C16H14O2, M = 238.27 g/mol, orthorhombic system, space group Pbca, a =
11.5681(6), b = 7.2752(3), c = 28.1081(15) Å, V = 2365.6(2) Å3, Z = 8, Dc = 1.338
g.cm-3, μ(Mo-Kα)= 0.087 mm-1, crystal dimension of 0.23 x 0.14 x 0.09 mm3. Data
were collected with a STOE IPDS-2T diffractometer and corrected for absorption
effects using indexed faces. The structure was solved by using SIR2011. The structure
refinement and data reduction was carried out with SHELXL. The non-hydrogen
atoms were refined anisotropically by full matrix least-squares on F2 values to final
R1 = 0.0322, wR2 = 0.0724 and S = 0.840 with 167 parameters using 2148
independent reflection (θ range = 1.45 - 25.25o). The hydrogen atom bonded to C6
was located and refined isotropically. The other hydrogen atoms were located from
expected geometry and were not refined. CCDC 894702 contains the supplementary
crystallographic data for this paper. These data can be obtained free of charge from
the
Cambridge
Crystallographic
Data
Centre
via
www.ccdc.cam.ac.uk/data_request/cif.
3. Results and discussion
8

We first optimized the conditions for the reaction of cyclohexanone (1; X = (CH2)2)
with benzaldehyde using various amines, as summarized in Table 1. Under solvent-
free conditions and in the presence of ultrasonic irradiation, Et3N, DABCO,
morpholine, and Et2NH (entries 1-4) did not cause significant formation of 3a (n = 1)
giving the respective bis compound as the major product. The chemoselectivity of the
reaction changed dramatically when pyrrolidine was used resulting in the formation of
73% of 3a (entry 5) in the presence of only 50 mol% of this organocatalyst. In the
absence of ultrasound (entry 6) or the amine (entry 7) reaction either gave lower
quantities of the product or was completely halted showing the promoting effect of
the irradiation and the amine.
Table 1
We then used the optimum solvent-free conditions (pyrrolidine/ultrasonic irradiation)
for the reactions of other ketones with various aldehydes (Table 2). Notably,
condensation of cyclopentanone (1; X = CH2) with benzaldehyde gave higher
amounts of 3a (n = 0) within the same period of sonication (entry 1). Other aromatic
aldehydes bearing electron releasing (entries 2-3), electron withdrawing (entries 4-5),
and heterocyclic residues (entries 6-7) behaved similarly and gave their respective
products within 4-7 minutes. Relatively lower yields were obtained when an aliphatic
aldehyde (entry 8) was used due to possible competitive side reactions.
Cyclopentanone showed higher reactivity in all cases resulting in more efficient
synthesis of its respective monoarylidenes and less amounts of the bis counterparts.
Table 2
9

We next extended the scope of the method by subjecting synthetically important
heterocyclic pyran-4-one (1; X = CH2O), piperidin-4-one (1; X = CH2NMe), and
thiopyran-4-one (1; X = CH2S) systems to the same reaction conditions. As a results,
condensations of these three ketones with various aldehydes gave good yields of
products 4-6, respectively, within short time periods of sonication (Table 3).
Table 3
The interesting point observed here is the chemoselectivity of the reaction which is
due to the use of equimolar amounts of the reactants and non-thermal energy source
provided by ultrasonic irradiation. These conditions help control the direction of the
process by mainly producing the desired products. In other words, if the reactions are
stopped at appropriate point of time, monoarylidenes are obtained as the major
products with no significant formation of their bis counterparts. This is due to the
mild conditions (a relatively weak base and ultrasound) of the reaction which
selectively cause deprotonation of 1 in competition with 3 so that formation of bis
products is avoided. This selectivity can be attributed to the fact that 3 is less prone to
deprotonation because of having less  hydrogens and already being conjugated. To
support this hypothesis, a 1:1 mixture of 1 and 3d (n = 1) was subjected to compete
for 4-ClC6H4CHO. As a result, 3e (n = 1) was exclusively obtained while TLC
showed no detectable formation of unsymmetrical bis product 3de after 15 minutes
sonication. Alternatively, 3de itself could be obtained by the reaction of 3d with 4-
ClC6H4CHO using similar conditions and longer irradiation time (Scheme 2).
Scheme 2.
10

The structure of known compounds was confirmed by comparison of their
spectroscopic and physical data with those reported in the literature. For new products
1
the doublet signals in their H NMR spectra appearing at chemical shift of about 3.5,
3.7, or 4.8 ppm for piperidin-4-one, thiopyran-4-one. or pyran-4-one products,
respectively, were particularly useful. These signals are realted to the O-CH2
4
methylenes of position 2 and show JH allylic couplings with the exocyclic methyne
hydrogens. The value of these couplings are about 2 Hz which is proportional to the E
absolute stereochemistry of the olefinic bonds. To validate the structure and the
stereochemistry of the products, a single crystal of 4a was prepared and subjected to
X-ray crystalography. The results shown in Figure 1 clearly supports the proposed
structure.
Fig. 1.
4. Conclusion
In summary, we have presented an efficient method for the preparation of
monoarylidenes of various homo- and heterocyclic ketones under ultrasonic
conditions using equimolar amounts of reactants. Products are prepared in one pot
with an easy workup, while no expensive or commercially unavailable reagents are
employed. It seems that ultrasonic irradiation has a key role in controlling the
selectivity of the reaction. In other words, since the reaction mixtures are mainly
homogeneous, the mechanical effects of ultrasonic irradiation can be excluded and
therefore one can conclude that a cavitational chemistry is responsible for the progress
of the reactions leading to a selective condensation, as was earlier discussed (scheme
2). As a result, formation of unwanted bis byproducts is avoided, a side reaction
which has always been a major limitation in other related methods. The procedure can
11

be used as a convenient platform for controlled and efficient synthesis of
unsymmetrical bis products.
Acknowledgment
The research council of the Islamic Azad University is greatly acknowledged for
financial support of this work.
Appendix. Supplementary data
Supplementary data associated with this article can be found, in the online version, at
http://dx.doi.org/10.1016/j.ultsonch.xxxx.xx.xxx.
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17

Scheme 1. General reaction for the synthesis of monoarylidenes.
18

Table 1
Optimization of the reaction conditions for the synthesis of 3a.
Entry
Conditions
)))), 10 min
)))), 10 min
)))), 10 min
)))), 10 min
)))), 4 min
60 min
Amine
Yield (%)a
1
Et3N
< 5
< 5
< 5
15
2
DABCO
morpholine
Et2NH
3
4
5
pyrrolidine
pyrrolidine
none
73
6
18
7
60 min
nil
a GC yields.
19

Table 2
Ultrasound promoted reactions of cycloalkanones with aldehydes.
Time (min) Yield (%)a
Entry Aldehyde
Product
n = 0/1
n = 0/1
1
C6H5CHO
4/4
91/73
3a
2
3
4
5
6
7
4-MeC6H4CHO
5/5
5/5
4/4
5/7
4/6
4/6
85/65
83/71
84/69
88/70
81/66
79/70
3b
4-MeOC6H4CHO
4-NO2C6H4CHO
4-ClC6H4CHO
3c
3d
3e
thienyl-2-carbaldehyde
furan-2-carbaldehyde
3f
3g
20

8
Me2CHCH2CHO
8/8
61/53
3h
a Isolated yields.
21

Table 3
Ultrasound promoted reactions of heterocyclic ketones with aldehydes.
Yield
(%)a
Entry Aldehyde
Product
Time (min)
1
2
3
4
2-naphthaldehyde
4
72
71
77
74
4a
4-MeC6H4CHO
3-FC6H4CHO
4-BrC6H4CHO
5
3
4
4b
4c
4d
5
6
7
C6H5CHO
10
8
62
65
70
5a
3-MeC6H4CHO
4-ClC6H4CHO
5b
5
5c
22

8
9
thienyl-2-carbaldehyde
2-MeC6H4CHO
8
3
75
70
5d
6a
10
3,4,5-(MeO)3C6H2CHO
3
68
6b
11
12
2-FC6H4CHO
2
3
75
65
6c
3-O2NC6H4CHO
6d
a Isolated yields.
23

Scheme 2. A mechanistic study using competitive reactions.
24

Fig. 1. Crystal structure of 4a. Displacement ellipsoids at 50% probability level.
25

 Ultrasonic irradiation causes efficient synthesis of monoarylidenes of ketones.
 Various products are directly obtained under solvent-free conditions.
 Catalytic amounts of the organocatalyst are enough for the reaction to proceed.
 No significant formation of the undesired bis by-products is observed.
 The procedure is applicable to both homo- and heterocyclic ketones.