Study of in situ generation of carbocationic system from trityl chloride (Ph3CCl) which efficiently catalyzed cross-aldol condensation reaction

Article abstract of DOI:10.1016/j.crci.2012.12.012

Organocatalyst trityl chloride (Ph₃CCl), by in situ formation of trityl carbocation with inherent instability, efficiently promotes the cross-aldol condensation reaction between cycloalkanones and arylaldehydes in solvent-free and homogeneous media to afford α,α′- bis(arylidene)cycloalkanones in high yields. Moreover, an attractive and plausible mechanism based on observations and the literature is proposed for the reaction.

Full text of DOI:10.1016/j.crci.2012.12.012

C. R. Chimie 16 (2013) 380–384
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´
Full paper/Memoire
Study of in situ generation of carbocationic system from trityl chloride
(Ph3CCl) which efficiently catalyzed cross-aldol condensation reaction
a
b
c
Abdolkarim Zare a, , Maria Merajoddin , Alireza Hasaninejad , Ahmad Reza Moosavi-Zare ,
*
Vahid Khakyzadeh d
a Department of Chemistry, Payame Noor University, PO BOX 19395-3697, Tehran, Iran
b Department of Chemistry, Faculty of Sciences, Persian Gulf University, 75169 Bushehr, Iran
c Department of Chemistry, University of Sayyed Jamaleddin Asadabadi, 6541835583 Asadabad, Iran
d Faculty of Chemistry, Bu-Ali Sina University, 6517838683 Hamedan, Iran
A R T I C L E I N F O
A B S T R A C T
Article history:
Organocatalyst trityl chloride (Ph3CCl), by in situ formation of trityl carbocation with
inherent instability, efficiently promotes the cross-aldol condensation reaction between
Received 8 May 2012
Accepted after revision 11 December 2012
Available online 20 January 2013
cycloalkanones and arylaldehydes in solvent-free and homogeneous media to afford a, -
a0
bis(arylidene)cycloalkanones in high yields. Moreover, an attractive and plausible
mechanism based on observations and the literature is proposed for the reaction.
Keywords:
´
ß 2013 Academie des sciences. Published by Elsevier Masson SAS. All rights reserved.
Trityl chloride (Ph3CCl)
Trityl carbocation
Organocatalyst
Cross-aldol condensation
a,
a0-Bis(arylidene)cycloalkanone
Solvent-free
1. Introduction
transformations based on new reactivity concepts have
been identified, often with no counterpart in the more
The use of small-molecule organocatalysts in organic
synthesis has flourished over the past decade [1–9].
However, the concept of organocatalysis has emerged as a
discrete strategy for addressing modern-day challenges in
chemistry. It has become widely appreciated that small-
moleculeorganiccatalystscan hold a wide rangeof practical
advantages relative to macromolecular, precious metal or
protic acidic catalysts, including air stability, low cost,
commercial availability, relative non-toxicity, green nature
and simple reaction conditions, and can promote a chemical
reaction through different activation modes [1–9]. With the
dramatic recent expansion of research efforts in organoca-
talysis throughout the world, synthetically useful
established catalysis regimens [1–9]. Triarylmethyl chlor-
ides (Ar3CCl) are an attractive class of small-molecule
organocatalysts, which have been utilized to promote a few
organic transformations by in situ formation of triaryl-
methyl carbocations [6–9]. It is noteworthy that the
inherent instability of carbocations has precluded up to
nowtheir usein catalysis with decent turnover numbers [7].
The aldol condensation reaction has been widely
applied for carbon–carbon bond formation in organic
synthesis [10–12]. Among them, the cross-aldol conden-
sation of cycloalkanones with arylaldehydes leading to
a,
a0-bis(arylidene)cycloalkanones [13], which have
attracted much attention due to their use as precursors
for the synthesis of pyrimidine derivatives [14], and their
intriguing biological activities such as antiangiogenic [15],
quinine reductase inducer [16], and cholesterol-lowering
properties [17]. Generally, the aldol condensation reaction
* Corresponding author. Tel.: +98 771 5559486; fax: +98 771 5559489.
E-mail address: abdolkarimzare@yahoo.com (A. Zare).
1631-0748/$ – see front matter ß 2013 Acade´mie des sciences. Published by Elsevier Masson SAS. All rights reserved.
http://dx.doi.org/10.1016/j.crci.2012.12.012

A. Zare et al. / C. R. Chimie 16 (2013) 380–384
381
Table 1
has been catalyzed by strong acids [18] and more likely by
bases [19]; however, in these conditions, the reactions
suffer from reverse and/or side reactions [20]. Moreover,
some metal ions with different ligands [21–25] and solid
acids [26,27] have been introduced as catalysts to replace
strong acids or bases. But most of these methods are
associated with one or more of the following drawbacks:
moderate yields, unwanted side reactions, need for
application of sealed ampoules or tubes, use of expensive,
unavailable and toxic catalysts, and application of an
additional energy (microwave). Although some catalysts
(mostly Brønsted and Lewis acids) for the cross-aldol
condensation of cycloalkanones with arylaldehydes lead-
The reaction of cylohexanone with m-nitrobenzaldehyde in the presence
of different amounts of Ph3CCl at various temperatures.
Entry Mol% of Ph3CCl Temperature (8C) Time (h) Yielda (%)
1
2
3
4
5
6
–
110
110
110
110
100
120
8
19
76
94
92
83
90
7.5
10
12.5
10
10
6
4.5
4.5
4.5
4.5
a
Isolated yield.
situ formation of trityl carbocation with inherent instabil-
ity from trityl chloride (Ph3CCl) which catalyzes the
reaction, and suggestion of a plausible mechanism based
on observations and the literature.
ing to
a,
a0-bis(arylidene)cycloalkanones are known,
newer catalysts continue to attract attention for their
difference with the others, high novelty and effectiveness.
In this work, we introduce a high novelty in the cross-
aldol condensation reaction between cycloalkanones and
arylaldehydes, and perform the reaction using trityl
chloride (Ph3CCl) as an efficient and homogeneous
small-molecule organocatalyst under solvent-free condi-
tions at 110 8C. Attractive points of this work are study of in
2. Results and discussion
At first, the condensation of cyclohexanone (1 mmol)
with m-nitrobenzaldehyde (2.1 mmol) was selected as a
model reaction (Scheme 1), and its behavior was studied in
O
O
CHO
O2N
NO2
Ph3CCl (10 mol%)
Solvent-free, 110 °C
4.5 h
2
+
NO2
94%
Scheme 1. The cross-aldol condensation between cyclohexanone and m-nitrobenzaldehyde catalyzed by Ph3CCl.
Table 2
The solvent-free cross-aldol condensation of cycloalkanones with aldehydes using Ph3CCl at 110 8C.
O
O
Ph3CCl (10 mol%)
2 RCHO
+
R
R
Solvent-free, 110 °C
( )n
( )n
Entry
n
R
Time (h)
Yielda (%)
M.p. (8C)
Found
Reported
1
1
1
1
2
2
2
2
2
2
2
2
2
2
2
2
3
3
3
C6H5
4
87
92
79
87
91
94
88
76
91
90
76
84
92
83
86
86
89
87
186-188
207-209
174-176
113-115
161-163
184-186
165-167
169-171
250-252
143-145
105-107
104-106
141-143
142-144
176-178
104-106
165-167
129-131
187-189 [13]
210-211 [25]
173-175 [13]
116-117 [22]
159 [21]
2
p-MeOC6H4
m-ClC6H4
C6H5
4
3
5.5
5.5
4
4
5
p-NO2C6H4
m-NO2C6H4
p-MeOC6H4
p-MeC6H4
p-Me2NC6H4
p-ClC6H4
m-ClC6H4
o-ClC6H4
2-Thienyl
2-Furyl
6
4.5
4
180-182 [13]
160-162 [25]
170 [22]
7
8
5.5
3.5
4
9
250-252 [30]
147-148 [22]
108-110 [13]
103-105 [26]
142-143 [31]
140-142 [13]
179-180 [25]
105-107 [13]
162-164 [13]
131-133 [13]
10
11
12
13
14
15
16
17
18
6
5
5
4.5
4.5
6
C6H5CH = CH
C6H5
3,4-(MeO)2C6H3
p-ClC6H4
3.5
4
a
Isolated yield.

382
A. Zare et al. / C. R. Chimie 16 (2013) 380–384
O
H
the presence of different molar ratios of Ph3CCl in the 100–
120 8C range under solvent-free conditions. The results are
displayed in Table 1. As it can be seen in Table 1, 10 mol% of
the organocatalyst was sufficient to promote the reaction
efficiently at 110 8C (Table 1, entry 3). Increasing the
amount of Ph3CCl or the temperature decreased the
reaction yield (Table 1, entries 4 and 6). The reaction
was also examined without catalyst in which the product
was obtained in low yield even after a long reaction time
(Table 1, entry 1).
+
Ph3CCl
O
H
CPh3
O
H
CPh3
H
Cl
II
I
O
O
After optimization of the reaction conditions, the
efficiency, the generality and the scope of the organoca-
OH
CPh3
talyst in the preparation of
a,
a0-bis(arylidene)cycloalk-
Cl
O
anones were assessed by the reaction of cycloalkanones
(cyclopentanone, cyclohexanone and cycloheptanone)
with different arylaldehydes including benzaldehyde as
well as aldehydes containing electron-withdrawing sub-
stituents, electron-releasing substituents or halogens
(Table 2). As Table 2 indicates, all reactions proceeded
efficiently and the desired products were obtained in high
to excellent yields and in logical reaction times (Table 2,
entries 1–12 and 16–18). Trityl chloride also successfully
catalyzed the reaction of cyclohexanone with p-dimethy-
laminobenzaldehyde (containing a basic group), hetero-
aromatic aldehydes and cinnamaldehyde (Table 2, entries
9 and 13–15). Thus, in this reaction, Ph3CCl was efficient
and general catalyst.
III
O
O
H
Ph3C
+
O
O
Cl
H
CPh3
Ph3COH
+
O
V
IV
Based on the literature reports related to the presented
reaction shown in Scheme 2, our mechanistic proposal is
that from the interaction of aldehyde and trityl chloride,
tautomers I and II could be generated via a reversible
reaction pathway [6–9].
In order to validate our proposal, benzaldehyde was
reacted with trityl chloride (in ratio of 1/1), and then IR, 1H
NMR spectra of the resulting interacted aldehyde functional
group of proposed tautomers I and II in the reaction mixture
were compared with those in benzaldehyde as follows.
According to the obtained FT-IR spectrum of the
resulting reaction mixture, stretching vibration of the
carbonyl of the aldehyde functional group slighlty shifts to
lower frequency because of the increased dipole moment
O
+
H2O
+ Ph3CCl
VI
O
H
O
Ph3CCl
+
+
H2O
character of carbonyl functionality: IR (nujol): n )
max (cm–1
of C5O in benzaldehyde (1705) decreased to (1697) in the
reaction mixture (Fig. 1).
α,α´
-Bis(arylidene)cycloalkanone
Scheme 2. The proposed mechanism for the cross-aldol condensation
Accordingly, in the 1H NMR spectra, the aldehyde
hydrogen as well as carbonyl carbon were deshielded,
which is in agreement with the increased single bond
character of carbonyl functional group observed in the FT-
d (ppm) of the
aldehydic hydrogen (9.78) increased to (10.04) in the
reaction mixture (Fig. 2).
UV (n-hexane): lmax (nm) of absorption of benzalde-
hyde and trityl chloride appears at 240 and 222,
respectively; however, lmax of the absorbtion of the
complexes of benzaldehyde and trityl cation was observed
at 245 (Fig. 3).
These results confirm that tautomer forms I and II are
present in the reversible reaction media. Moreover, the
cationic tautomers I and II have been introduced by
Kusumoto et al. for the first time [28]. These tautomer
forms act as activated aldehyde, and then react with
reaction using Ph3CCl.
cyclohexanone providing III, which converts to IV by
proton transfer. Intermediate IV can be converted to V by
removing Ph3COH in a reversible reaction. Afterward, V
and Ph3COH produce intermediate VI, Ph3CCl and H2O. VI
accordingly reacts with another activated aldehyde by
IR spectra: 1H NMR (300 MHz, CDCl3):
Ph3CCl to afford the corresponding
a,
a0-bis(arylidene)cy-
cloalkanone. The suggested mechanism is confirmed by
the literature [29], and also by the fact that Ph3CCl was
completely recovered unchanged and Ph3COH could not be
identified after completion of the reaction as it could be
observed on TLC by comparison with pure authentic
samples. In another study, to demonstrate that Ph3CCl
cannot convert to Ph3COH and HCl by the water produced
during the reaction, and consequently HCl is not the real

A. Zare et al. / C. R. Chimie 16 (2013) 380–384
383
Fig. 1. IR spectra of benzaldehyde as well as the mixture of benzaldehyde and Ph3CCl (in ratio of 1/1).
Fig. 3. UV spectra of benzaldehyde, Ph3CCl and the complexes of
benzaldehyde and Ph3CCl (in ratio of 1/1).
non-toxicity as well as low cost of the catalyst, and good
compliance with the green chemistry protocols which
a0
makes it an attractive procedure for the synthesis of a, -
bis(arylidene)cycloalkanones as an important class of
organic compounds.
Fig. 2. 1H NMR spectra of the formyl hydrogen of benzaldehyde,
separately as well as in the mixture of benzaldehyde and Ph3Cl (in
ratio of 1/1).
4. Experimental
catalyst of the process, the solvent-free condensation of
cyclohexanone with 3-nitrobenzaldehyde was examined
in the presence of the expected amount of HCl produced by
the reversible reaction of Ph3COH with H2O, at 110 8C, in
which the product was obtained in 48% within 8 h. The
reaction was also tested using Ph3COH wherein the
reaction yield was 19% after 8 h. These evidences showed
that HCl is not produced from Ph3CCl in these conditions,
and that Ph3CCl is the real catalyst of this transformation.
4.1. General
All chemicals were purchased from Merck or Fluka
Chemical Companies. All known compounds were identi-
fied by comparison of their melting points and spectral
data with those reported in the literature. Progress of the
reactions was monitored by TLC using silica gel SIL G/UV
254 plates. The 1H NMR (500 MHz) and 13C NMR
(125 MHz) were run on a Bruker Avance DPX, FT-NMR
spectrometer. UV spectra were run on a T8 UV-VIS
spectrometer, PG instruments Ltd. Melting points were
recorded on a Bu¨chi B-545 apparatus in open capillary
tubes.
3. Conclusion
In summary, we have shown that organocatalyst trityl
chloride, by in situ generation of carbocationic system,
efficiently catalyzed the cross-aldol condensation reac-
tion. The promising points for the presented protocol are
simple and clean reaction profile, efficiency, generality,
high yields, reaction in solvent-free and homogeneous
media without side reactions, economic availability,
4.2. General procedure for the cross-aldol reaction
A
mixture of cycloalkanone (1 mmol), aldehyde
(2.1 mmol) and trityl chloride (0.028 g, 0.1 mmol) in a test
tube connected to a reflux condenser, was stirred at 110 8C,

384
A. Zare et al. / C. R. Chimie 16 (2013) 380–384
and the reaction progress was monitored by TLC. After
completion of the reaction, the mixture was cooled to room
temperature, petroleum ether (10 mL) was added to it,
refluxed and stirred for 3 min, and filtered to separate the
catalyst. The solid residue (crude product) was purified by
recrystallization from EtOH (95%) or column chromatog-
raphy on silica gel eluted with n-hexane/EtOAc (1/5) to
(m, 8H); 13C NMR (125 MHz, CDCl3):
d = 28.4, 29.1, 129.2,
131.1, 134.6, 134.7, 135.0, 142.4, 199.3.
Acknowledgements
The authors gratefully acknowledge financial support of
this work by the Research Council of Payame Noor
University.
give the pure
a,
a0-bis(arylidene)cycloalkanone.
4.3. Selected spectral data of the products
References
2,5-Bis(3-chlorobenzylidene)cyclopentanone (Table
2, entry 3): 1H NMR (500 MHz, CDCl3):
d
= 3.01 (s, 4H),
7.29–7.33 (m, 4H), 7.39–7.42 (m, 2H), 7.43 (s, 2H), 7.51 (t,
J = 1.2 Hz, 2H); 13C NMR (125 MHz, CDCl3):
= 27.0, 128.6,
[1] E.N. Jacobsen, D.W.C. MacMillan, Proc. Natl Acad. Sci. U S A 107 (2010)
20618.
[2] M.R. Poor Heravi, P. Aghamohammadi, C. R. Chimie 15 (2012) 448.
[3] V. Polshettiwar, R.S. Varma, Tetrahedron 66 (2010) 1091.
[4] N. Azizi, E. Saki, M. Edrisi, C. R. Chimie 14 (2011) 973.
[5] N. Iranpoor, H. Firouzabadi, N. Nowrouzi, D. Khalili, Tetrahedron 65
(2009) 3893.
[6] A. Khazaei, M.A. Zolfigol, A.R. Moosavi-Zare, A. Zare, M. Khojasteh, Z.
Asgari, V. Khakyzadeh, A. Khalafi-Nezhad, Catal. Commun. 20 (2012)
54.
[7] A. Khazaei, M.A. Zolfigol, A.R. Moosavi-Zare, A. Zare, A. Parhami, A.
Khalafi-Nezhad, Appl. Catal. A: Gen. 386 (2010) 179.
[8] A. Khalafi-Nezhad, A. Parhami, A. Zare, A.R. Moosavi Zare, A. Hasani-
nejad, F. Panahi, Synthesis (2008) 617.
[9] A. Khalafi-Nezhad, A. Parhami, A. Zare, A. Nasrollahi Shirazi, A.R.
Moosavi Zare, A. Hasaninejad, Can. J. Chem. 86 (2008) 456.
[10] B.M. Trost, I. Fleming, Comprehensive organic synthesis, 2, Pergamon
Press, Oxford, 1991.
d
129.6, 130.5, 130.7, 132.5, 135.3, 137.1, 138.6, 196.0.
2,6-Bis(3-chlorobenzylidene)cyclohexanone (Table 2,
entry 11): 1H NMR (500 MHz, CDCl3):
d = 1.69 (quintet,
J = 5.7 Hz, 2H), 2.78 (t, J = 5.7 Hz, 4H), 7.30–7.37 (m, 6H),
7.41 (s, 2H), 7.62 (t, J = 1.2 Hz, 2H); 13C NMR (125 MHz,
CDCl3): 23.7, 27.9, 126.3, 127.9, 129.3, 130.4, 130.9, 133.2,
135.8, 137.8, 188.9.
2,6-Bis(2-chlorobenzylidene)cyclohexanone (Table 2,
entry 12): 1H NMR (500 MHz, CDCl3):
d = 1.75 (quintet,
J = 5.8 Hz, 2H), 2.78 (t, J = 5.8 Hz, 4H), 7.28 (m, 4H), 7.34 (d,
J = 3.4, 2H), 7.45 (d, J = 3.3 Hz, 2H), 7.89 (t, J = 1.2 Hz, 2H);
[11] R. Mahrwald, D.A. Evans (Foreword by) (Eds.), Modern Aldol Reactions,
Wiley-VCH, Germany, Weinheim, 2004.
13C NMR (125 MHz, CDCl3):
d = 23.2, 28.7, 126.8, 130.8,
130.9, 131.0, 134.5, 135.0, 135.5, 138.3, 189.2.
(2E,6E)-2,6-Bis((E)-3-phenylallylidene)cyclohexa-
none (Table 2, entry 15): 1H NMR (500 MHz, CDCl3):
[12] N.B. Pathan, A.M. Rahatgaonkar, M.S. Chorghade, Catal. Commun. 12
(2011) 1170.
[13] A. Hasaninejad, A. Zare, L. Balooty, H. Mehregan, M. Shekouhy, Synth.
Commun. 40 (2010) 3488.
d
= 1.85 (quintet, J = 5.8 Hz, 2H), 2.81 (t, J = 5.8 Hz, 4H), 6.97
[14] J. Deli, Pharmazie 39 (1984) 539.
[15] T.P. Robinson, R.B. Hubbard, T.J. Ehlers, J.L. Arbiser, D.J. Goldsmith, J.P.
Bowen, Bioorg. Med. Chem. 13 (2005) 4007.
[16] A.T. Dinkova-Kostova, C. Abeygunawardana, P. Talalay, J. Med. Chem.
41 (1998) 5287.
(d, J = 15.4 Hz, 2H), 7.10 (dd, 2H, J = 15.4, 1.2 Hz), 7.28 (m,
2H), 7.36 (m, 4H), 7.48–7.54 (m, 6H); 13C NMR (125 MHz,
CDCl3):
d = 22.5, 27.8, 124.7, 124.8, 127.5, 129.3, 135.9,
136.8, 137.3, 141.4, 188.3.
(2E,7E)-2,7-Dibenzylidenecycloheptanone (Table 2,
entry 16): 1H NMR (500 MHz, CDCl3):
[17] C. Piantadosi, I.H. Hall, J.L. Irvine, G.L. Carlson, J. Med. Chem. 16 (1973)
770.
[18] R.L. Reeves, in : S. Patai (Ed.), Chemistry of carbonyl group, Wiley
Intersciences, New York, 1966.
d = 2.03 (br, s, 4H),
2.75 (br, s, 4H), 7.37 (t, J = 7.2 Hz, 2H), 7.43 (s, 2H), 7.45 (m,
4H), 7.51 (d, J = 7.5 Hz, 4H); 13C NMR (125 MHz, CDCl3):
[19] J.T. Li, G.F. Chen, J.X. Wang, T.S. Li, Synth. Commun. 29 (1999) 965.
[20] L. Schriner, T. Kurosawa, J. Am. Chem. Soc. 52 (1930) 2538.
[21] K. Irie, K. Watanabe, Bull. Chem. Soc. Jpn. 53 (1980) 1366.
[22] N. Iranpoor, F. Kazemi, Tetrahedron 54 (1998) 9475.
[23] T. Nakano, S.J. Trifune, S. Umano, A. Inada, Y. Ishill, M. Ogawa, J. Org.
Chem. 52 (1987) 2239.
[24] Y. Aoyama, Y. Tanaka, T. Yoshida, H. Toi, H. Ogoshi, J. Organomet. Chem.
329 (1987) 251.
[25] M. Zhang, L. Wang, J. Shao, Q. Zhong, Synth. Commun. 27 (1997) 351.
[26] L.T. An, J.P. Zou, L.L. Zhang, Catal. Commun. 9 (2008) 349.
[27] P. Salehi, M. Dabiri, M.A. Zolfigol, M.A.B. Fard, J. Braz. Chem. Soc. 15
(2004) 773.
[28] M. Oikawa, H. Yoshizaki, S. Kusumoto, Synlett 757 (1998).
[29] G. Mohammadi Ziarani, A. Badiei, A. Abbasi, Z. Farahani, Chin. J. Chem.
27 (2009) 1537.
[30] M.A. Bigdeli, G.H. Mahdavinia, S. Jafari, H. Hazarkhani, Catal. Commun.
8 (2007) 2229.
d
= 28.5, 29.3, 128.7, 128.9, 129.9, 136.1, 136.4, 142.2,
199.9.
(2E,7E)-2,7-Bis(3,4-dimethoxybenzylidene)cyclo-
heptanone (Table 2, entry 17): 1H NMR (500 MHz, CDCl3):
= 2.05 (br, s, 4H), 2.77 (br, s, 4H), 3.91 (s, 6H), 3.96 (s, 6H),
d
6.94 (d, J = 8.5 Hz, 2H), 7.05 (s, 2H), 7.12 (d, J = 8.5 Hz, 2H),
7.39 (s, 2H); 13C NMR (125 MHz, CDCl3): 28.7, 29.1, 56.3,
56.4, 111.5, 113.3, 123.1, 129.2, 135.9, 140.5, 149.2, 149.7,
199.9.
(2E,7E)-2,7-Bis(4-chlorobenzylidene)cyclohepta-
none (Table 2, entry 18): 1H NMR (500 MHz, CDCl3):
d
= 2.00 (br, s, 4H), 2.71 (br, s, 4H), 7.38 (s, 2H), 7.41–7.45
[31] L. Wang, J. Sheng, H. Tian, J. Han, Z. Fan, C. Qian, Synthesis (2004) 3060.