Nano-TiO2: an eco-friendly and re-usable catalyst for the one-pot synthesis of β-acetamido ketones

Article abstract of DOI:10.1515/znb-2009-0318

Nano-TiO₂ as an efficient, eco-friendly and reusable catalyst was applied for the one-pot synthesis of β-acetamido ketones. In this improved procedure, an aryl aldehyde, an aryl ketone, acetyl chloride and acetonitrile were condensed in the pre

Full text of DOI:10.1515/znb-2009-0318

Note
347
of TiO scatter light so strongly that they can be used
Nano-TiO : an Eco-friendly and
Re-usable Catalyst for the One-pot
Synthesis of β-Acetamido Ketones
2
2
to produce films of high capacity. In addition, TiO is
2
chemically inert and its oral LD for rats is higher than
5
0
−
1
10000 mg kg [19].
The high surface area-to-volume ratio of metal ox-
ide nanoparticles is mainly responsible for their cat-
alytic properties. High yield, selectivity and recycla-
bility have been reported for a variety of nanocatalyst-
Bi Bi Fatemeh Mirjalili and Ali Akbari
Department of Chemistry, Yazd University,
P. O. Box 89195-741, Yazd, Iran
Reprint requests to Dr. Bi Bi Fatemeh Mirjalili.
Fax: +98 351 8210644.
based organic reactions. TiO nanoparticles have been
2
widely investigated in the past decades due to their
multiple potential applications, such as solar energy
conversion, photocatalysts, sensors, and photochromic
E-mail: fmirjalili@yazduni.ac.ir
Z. Naturforsch. 2009, 64b, 347 – 350;
received December 10, 2008
devices. TiO has three well-known crystallographic
2
phases in nature: anatase, rutile, and brookite. Among
these, anatase has been proved to have excellent chem-
ical and physical properties for environmental purifi-
Nano-TiO as an efficient, eco-friendly and reusable cata-
2
lyst was applied for the one-pot synthesis of β-acetamido ke-
tones. In this improved procedure, an aryl aldehyde, an aryl
ketone, acetyl chloride and acetonitrile were condensed in cation and many other uses. In continuation of our uti-
the presence of the catalyst at room temperature.
lization of solid acids in organic synthesis [20– 26],
we became interested in the synthesis of β-acetamido
Key words: Nano-TiO , One-pot Reactions,
2
ketones using nano-TiO as an efficient, re-usable and
2
Multi-component Reactions, β-Acetamido
Ketones, Re-usable Catalyst
eco-friendly nano catalyst.
Results and Discussion
To find the optimal conditions, the synthesis of
β-acetamido-β-phenyl-propiophenone was used as a
model reaction. A mixture of benzaldehyde (2 mmol),
Introduction
β-Acetamido ketones are valuable building blocks acetophenone (2 mmol), acetyl chloride (0.5 mL) and
for the preparation of β-amino ketones or β-amino acetonitrile (2 mL) was stirred under various reac-
alcohols such as the antibiotic nikkomycins [1] and tion conditions (Table 1). In the presence of 12 mol-
neopolyoxines [2]. α-Acetamido ketones are obtained % of TiO , β-acetamido-β-phenyl-propiophenonewas
2
in the Dakin-West reaction [3] and β-acetamido ke- obtained in moderate yield after 12 h, while excel-
tones by the Iqbal route. In the latter, an aromatic alde- lent results were obtained in the presence of 8 mol-
hyde, an enolizable ketone and acetonitrile are con- % of nano-TiO after 12 h. Using more than 8 mol-
2
densed in the presence of acetyl chloride and a catalytic % TiO2 nanoparticles has less effect on the yield
amount of an acid [4]. Recently, many catalysts such and time of the reaction. To generalize this methodol-
as silica sulfuric acid [5], H P W O [6], ZnO [7], ogy, we subjected a series of aromatic aldehydes and
6
2
18 62
sulfated zirconia [8], some heteropoly acids [9], silica- enolizable ketones having electron-donating as well
supported H PW O [10], nano-ZnO [11], sulfamic as electron-withdrawing substituents under the opti-
3
12 40
acid [12], Sc(OTf) [13], SnCl ·2H O [14], Zeolite mized reaction conditions (Table 2). Acetylation of
3
2
2
Hβ [15], ZrOCl · 8H O [16], Mg(HSO ) [17], and an aromatic hydroxyl group was observed when us-
2
2
4 2
Nafion-H [18] have been applied in this one-pot re- ing p-hydroxybenzaldehyde. 4-Dimethylamino-benz-
action. However, some of these methods employ long aldehyde, however, was inert under the present reaction
reaction times [13] or harsh reaction conditions [5 – conditions.
7
, 10]. Thus, the need for the development of new pro-
The preparative efficacy of this one-pot synthesis
tocols is evident. TiO as a white pigment is used in was further checked by five-fold scaling-up of the reac-
2
the manufacture of paint and of surface coatings on pa- tion of benzaldehyde with acetophenone and the other
per and as a filler in rubber and plastics. Fine particles ingredients which proceeded with an 88 % yield. The
0
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348
Note
Table 1. Optimization of re-
action conditions for one-pot
formation of β-acetamido ke-
tones.
Entry
Catal. (mol-%)
ZrOCl2 ·8H2O (20)
Silica sufuric acid (78)
H3[PW12O40]
ZnO nanoparticles (10)
ZnO (50)
Nafion-H (500 mg)
Sc(OTf)3 (10)
H6P2W18O62 (0.14)
–
TiO2 (5)
TiO2 (16)
TiO2 (8)
TiO2 (12)
TiO2 (12)
TiO2 (12)
Time (h)
5
1.1
1
1
6
Cond. / Yield (%)a
Ref.
[16]
[5]
[10]
[11]
[7]
[18]
[13]
[6]
–
–
–
–
–
–
–
–
–
b
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
r. t. / 90
◦
80 C / 91
◦
b
80 C / 65
r. t. / 83
◦
80 C / 90
4
r. t. / 96
r. t. / 82
30
0.5
12
12
12
12
12
18
24
12
12
12
12
18
24
12
12
◦
80 C / 86
r. t. / 15
r. t. / 30
r. t. / 48
r. t. / 53
r. t. / 71
r. t. / 72
r. t. / 73
r. t. / 78
r. t. / 93
r. t. / 92
r. t. / 93
r. t. / 94
r. t. / 93
r. t. / 88
r. t. / 85
0
1
2
3
4
5
6
7
8
9
0
1
2
3
Nano-TiO2 (5)
Nano-TiO2 (8)
Nano-TiO2 (12)
Nano-TiO2 (16)
Nano-TiO2 (12)
Nano-TiO2 (12)
–
–
–
–
–
–
nd
Nano-TiO2 (12), 2 run
Nano-TiO2 (12), 3 run
a
Isolated yield; b yield after chro-
rd
matographic purification.
a
Table 2. Nano-TiO -catalyzed formation of β-acetamido ketones.
2
Entry Product (3)b
Yield (%)
Nano-TiO2/TiO2
m. p ( C)
◦
reported Crystallization solvent
m. p. ( C)
Ref.
◦
1
2
3
4
1
2
3
4
5
6
7
8
9
0
R , R , R =H, R =Ph
93/53
92/75
94/62
88/57
92/60
94/86
86/60
88/60
89/68
80/53
105 – 106 104 – 105 EtOAc-petroleum ether (20 : 80) [16]
118 – 119 118 – 120 Ethanol-water (30 : 70)
135 – 136 135 – 137 Ethanol-water (40 : 60)
193 – 194 194 – 195 EtOAc-petroleum ether (20 : 80) [16]
111 – 113
84 – 85
234 – 236 236 – 237 Ethanol-water (40 : 60)
109 – 110 110 – 112 EtOAc-petroleum ether (20 : 80) [16]
155 – 157 154 – 157 Ethanol-water (20 : 80)
142 – 143 141 – 143 Ethanol-water (20 : 80)
1
2
3
4
R , R , R =H, R =4-NO2-C6H4
[9, 18]
[9]
1
2
3
4
R =Cl, R , R =H, R =Ph
2
1
3
4
R =NO2, R , R =H, R =Ph
1
2
3
4
R , R =H, R =CH3, R =Ph
112
EtOAc-petroleum ether (20 : 80) [16]
1
2
3
4
R , R =H, R =CH3, R =4-NO2-C6H4
83 – 85 Ethanol-water (40 : 60)
[9]
[18, 27]
1
2
3
4
R , R =H, R =CO2CH3, R =Ph
1
2
3
4
R , R =H, R =OCH3, R =Ph
1
3
2
4
R , R =H, R =NO2, R =4-NO2-C6H4
[6]
[5]
1
2
3
4
1
R , R =H, R =Cl, R =4-Cl -C6H4
a
Isolated yield; b all the products are known and were characterized by IR and H NMR spectroscopy and by comparison of their physical
1
properties with those reported in the literature.
re-usability of the nano-TiO catalyst was also exam- treatment with CHCl removed tars more efficiently
2
3
ined. To this end, after each run the product was dis- from the catalyst surface This catalyst was re-usable,
solved in ethanol, filtered, and the residue (catalyst) although a gradual decline of activity was observed
was washed with CHCl and re-used. Apparently, the (Table 1, entries 22 and 23).
3
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Note
349
CH
3
COHN
O
Nano-TiO2, 8 mol-%
CH CN, PhCOCl
3
r. t., 72 h
CH3
82 %
NO
2
O
Nano-TiO2, 8 mol-%
No Reaction
O
CH
3
CH CN, r. t., 12 h
3
CH
3
COO
O
NO2
Nano-TiO2, 8 mol-%
+
+
CHO
3
CH COCl, r. t., 12 h
CH
3
40 %
H
CH3
NO2
0 %
NO
2
CH
3
Nano-TiO2, 8 mol-%
Ac O, CH CN,
OAc
OAc
+
NO
2
CO CH
3
2
3
r. t., 12 h
CH
3
8
7 %
Scheme 1.
1
00 %
Previously, three types of mechanisms for forma- up, improved yields, clean reactions, and low loading
tion of β-acetamido ketones by the Iqbal procedure of catalyst.
have been proposed [6, 7, 9, 11, 18, 19]. In some cases
[
7, 18, 19], a β-acetoxy ketone was offered as an in- Experimental Section
termediate product that was converted into the β-
acetamido ketone with acetonitrile. In our investiga-
tion, when no acetonitrile was present in the medium,
no β-acetoxy ketone was formed, and only a crossed
aldol condensation reaction occurred. In the prepa-
ration of β-acetamido ketone, no β-acetoxy ketone
was obtained as a by-product. Besides, a mixture of
chalcone, acetyl chloride and acetonitrile in the pres-
ence of catalyst failed to generate any β-acetamido
ketone.
General
The organic materials were purchased from Sigma-
Aldrich and Merck and were used without any additional
purification. All compounds gave satisfactory spectroscopic
data. A Bruker (DRX-400 Avance) NMR spectrometer was
used to record the H NMR and C NMR spectra. All NMR
spectra were determined in CDCl at ambient temperature.
1
13
3
Nano-TiO which was used as catalyst consists of anatase
2
(
plus some amorphous phase) with a specific BET surface
2
−1
area of 90 m g and ellipsoids with a 35 nm long axis and
In the absence of acetyl chloride or benzoyl chlo- 15 nm diameter. TiO2 nano-powders were extracted from a
ride, the reaction failed to provide the desired prod- TiO2 sol (TW01, Posshesh-haye Nanosakhtar Co., Iran). The
β-acetamido ketone products are known and were character-
ucts, obviously indicating that they play a necessary
role in this reaction, although not involved in the fi-
nal product. When benzyl cyanide or phenyl cyanide
was used instead of acetonitrile, the corresponding
β-amido ketones, namely a β-phenylacetamido ke-
tone or β-benzamido ketone were obtained. Note
1
ized by IR and H NMR spetroscopy and comparison of their
physical properties with those reported in the literature.
General procedure for the synthesis of β-acetamido ketones
To a stirred suspension of nano-TiO (8 mol-%) in ace-
2
that neither a mixture of 4-methylbenzaldehyde, 4- tonitrile (2 mL) were added an aldehyde (2 mmol), an eno-
nitroacetophenone, acetic anhydride and acetonitrile in lizable ketone (2 mmol) and acetyl chloride (0.5 mL). The
reaction mixture was stirred at ambient temperature for 12 h.
The progress of the reaction was monitored by TLC. Af-
ter 12 h, 3 mL of ethanol was added to the cold reaction mix-
ture, stirred for 2 min, and the catalyst was recovered by fil-
the presence of nano-TiO , nor a mixture of 4-methyl
2
benzaldehyde acylal, 4-nitroacetophenone and nano-
TiO in acetonitrile could produce any of the corre-
2
sponding β-acetamido ketones (Scheme 1).
tration and washed with ethanol. Then, 50 mL of cold water
was added to the filtrate, the precipitated product was filtered
and recrystallized from a mixture of ethanol and water.
Conclusion
We have reported an efficient procedure for the syn-
Acknowledgement
thesis of β-acetamido ketones using nano-TiO as a
2
re-usable, eco-friendly and efficient heterogeneous cat-
Financial support for this work by the Research Council
alyst. Some advantages of this protocol are easy work- of Yazd University is gratefully acknowledged.
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350
Note
[
[
1] D. P. Henderson, M. C. Shelton, I. C. Cotterill, E. J.
[15] R. P. Bhat, V. P. Raje, V. M. Alexander, S. B. Patil, S. D.
Samant, Tetrahedron Lett. 2005, 46, 4801.
[16] R. Ghosh, S. Maiti, A. Chakraborty, S. Chakraborty,
A. Mukherjee, Tetrahedron 2006, 62, 4059.
[17] H. R. Shaterian, A. Hosseinian, M. Ghashang, Can. J.
Chem. 2008, 86, 376.
Toone, J. Org. Chem. 1997, 62, 7910.
2] M. Uramoto, K. Kobinata, K. Isono, T. Higashijima,
T. Miyazawa, E. E. Jenkins, J. A. McCloskey, Tetrahe-
dron Lett. 1980, 21, 3395.
[
[
3] H. D. Dakin, R. West, J. Biol. Chem. 1982, 78, 745.
4] M. M. Reddy, B. Bhatia, J. Iqbal, Tetrahedron Lett.
[18] T. V. Yakaiah, B. P. Lingaiah, G. V. Reddy, B. Narsaiah,
P. Shanthan Rao, Arkivoc 2007, 13, 227.
1995, 36, 4877.
[
[
[
5] M. M. Khodaei, A. R. Khosropour, P. Fattahpour,
Tetrahedron Lett. 2005, 46, 2105.
6] M. M. Heravi, L. Ranjbar, F. Derikvand, F. Bamohar-
ram, Catal. Commun. 2007, 8, 289.
7] M. T. Maghsoodlou, A. Hassankhani, H. R. Shaterian,
S. M. Habibi-Khorasani, E. Mosaddegh, Tetrahedron
Lett. 2007, 48, 1729.
[19] N. N. Greenwood, A. Earnshaw, Chemistry of the
Elements, Pergamon Press. 1985, p. 1118.
[20] B. Sadeghi, B. F. Mirjalili, M. M. Hashemi, Tetrahe-
dron Lett. 2008, 49, 2575.
[21] A. R. Hajipour, A. Zarei, L. Khazdooz, B. F. Mirjalili,
N. Sheikhan, S. Zahmatkesh, A. E. Ruoho, Synthesis
2005, 20, 3644.
[22] A. R. Hajipour, B. F. Mirjalili, A. Zarei, L. Khazdooz,
A. E. Ruoho, Tetrahedron Lett. 2004, 45, 6607.
[23] B. F. Mirjalili, M. A. Zolfigol, A. Bamoniri, M. A.
Karimi-Zarchi, Z. Zaghaghi, M. Parvaideh, J. Iran.
Chem. Soc. 2007, 4, 340.
[24] A. Bamoniri, B. F. Mirjalili, M. A. Zolfigol,
I. Mohammadpoor-Baltork, J. Iran. Chem. Soc.
2007, 4, 332.
[25] B. F. Mirjalili, A. Bamoniri, A. Akbari, Tetrahedron
Lett. 2008, 49, 6454.
[26] B. F. Mirjalili, A. Bamoniri, M. Alipour, M. A. Karimi
Zarchi, Z. Naturforsch. 2008, 63b, 1421.
[
8] B. Das, M. Krishnaiah, K. Laxminarayana, K. R.
Reddy, J. Mol. Catal. A: Chem. 2007, 270, 284.
9] E. Rafiee, F. Tork, M. Joshaghani, Bioorg. & Med.
Chem. Lett. 2006, 16, 1221.
[
[
[
[
[
[
10] E. Rafiee, F. Shahbazi, M. Joshaghani, F. Tork, J. Mol.
Catal. A: Chem. 2005, 242, 129.
11] Z. Mirjafary, H. Saeidian, A. Sadeghi, F. Matloubi
Moghaddam, Catal. Commun. 2008, 9, 299.
12] M. Heravi, L. Ranjbar, F. Derikvand, F. F. Bamohar-
ram, J. Mol. Catal. A: Chem. 2007, 276, 226.
13] G. Pandey, R. P.Singh, A. Garg, V. K. Singh, Tetrahe-
dron Lett. 2005, 46, 2137.
14] L. Nagarapu, R. Bantu, R. Puttireddy, Appl. Catal. A:
Gen. 2007, 332, 304.
[27] A. Hassankhani, M. T. Maghsoodlou, S. M. Habibi-
Khorassani, H. Hosseini-Mahdiabad, G. Marandi,
Arkivoc 2008, 2, 134.
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