ZnO nanofluid as a structure base catalyst for chemoselective amidation of aliphatic carboxylic acids

Article abstract of DOI:10.1016/j.catcom.2011.09.023

ZnO nanofluids were synthesized and utilized as a new reaction media in the preparation of amides via direct amidation of aliphatic carboxylic acids with primary amines under solvent-free conditions. High yields and good selectivity are achieved with this psudo-homogeneous catalyst, while the recovered nanoZnO was reusable.

Full text of DOI:10.1016/j.catcom.2011.09.023

Catalysis Communications 16 (2011) 194–197
Contents lists available at SciVerse ScienceDirect
Catalysis Communications
journal homepage: www.elsevier.com/locate/catcom
Short Communication
ZnO nanofluid as a structure base catalyst for chemoselective amidation of aliphatic
carboxylic acids
Fatemeh Tamaddon ⁎, Fatemeh Aboee, Alireza Nasiri
Department of Chemistry, Faculty of Science, Yazd University, Yazd 89195-741, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 13 July 2011
Received in revised form 19 September 2011
Accepted 19 September 2011
Available online 28 September 2011
ZnO nanofluids were synthesized and utilized as a new reaction media in the preparation of amides via direct
amidation of aliphatic carboxylic acids with primary amines under solvent-free conditions. High yields and
good selectivity are achieved with this psudo-homogeneous catalyst, while the recovered nanoZnO was
reusable.
©
2011 Elsevier B.V. All rights reserved.
Keywords:
Nanofluids
ZnO
Carboxylic acids
Acylation
Solvent-free
Direct amidation
1
. Introduction
melting point make it more attractive catalyst. Various nanopowder,
nanoparticles, and nanofluids of ZnO have been artificially prepared
by sol–gel processing and controlled hydrolysis of zinc halides, zinc
alkoxides or zinc acetate [11–14]. The prepared nanoZnO by different
processes vary in morphology, surface area, porosity, crystalinity, parti-
cle size, and hence catalytic properties. Recently, ZnO nanofluids have
been prepared by dispersing of ZnO nanoparticles in glycerol as a base
fluid and used as antibacterial agent [15].
Amides are among the most useful building blocks of natural
products and biologically active compounds including drugs, pep-
tides, lubricants, polymers, and agrochemicals [1,16–21]. Among
the various developed synthetic methods, acylation of amines with
acyldonors such as acid chlorides, anhydrides, esters, acyl azides
and carboxylic acids have been widely used to produce amides
[17–28]. Despite the less reactivity of acids, direct amidation is still
the most favorite industrial process from both atom economy and
environmental points of view. The low reactivity of carboxylic acid
as acyldonor has been improved by the in situ activation of COOH
group either in the presence of coupling agents, supports or catalysts
[17–21]. Metal oxides are among the catalysts have been used as ac-
tivating agents for carboxylic acids in acylation reactions [18–28].
We have recently used ZnO [29], nanoZnO [14], and other heteroge-
neous catalysts in a variety of organic transformations [30–32]. The
drawbacks of amidation methodologies, high affinity of ZnO towards
carboxyl group, and the similarity of nanofluids to homogeneous cat-
alysts stimulated us to investigate the direct synthesis of amides
using preparative ZnO nanofluids (Scheme 1).
Metal oxide promoted reactions at heterogeneous conditions is a
proficient field of chemistry which is highlighted by the use of various
nanosized catalysts [1–5]. Metal oxide surfaces exhibit both acid and
base properties. These dualities make metal oxides as excellent ad-
sorbent and activator of organic compounds. The promising factors
which govern on the catalytic activity of metal oxides are the nature
of metal cation, morphology, particle size, and surface area of them.
Recent development on the nanoscience has provided great oppor-
tunity for the surface modification and chemical composition of
nanosized metal oxides [5]. Metal oxide nanofluids are among the
newer versions of nanocatalysts [6], which mimic the homogeneous
catalysts make the maximum contact between starting materials and
catalyst. They are colloidal suspension of nano-sized metal oxides in
a base fluid and due to the better ability of dispersion they can be
emerged as robust, active, and high surface area catalysts.
Zinc oxide is a low-priced versatile metal oxide which in both com-
mercial and nano forms has been utilized as a professional environmen-
tally benign catalyst in various organic transformations [7–11]. Its high
heat capacity, high heat conductivity, low thermal expansion, and high
⁎
Corresponding author. Tel.: +98 3518122666; fax: +98 3518210644.
E-mail addresses: ftamaddon@yazduni.ac.ir (F. Tamaddon),
ftamaddon@yazduni.ac.ir (F. Aboee), Nasiri_62@yahoo.com (A. Nasiri).
1566-7367/$ – see front matter © 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.catcom.2011.09.023

F. Tamaddon et al. / Catalysis Communications 16 (2011) 194–197
195
ZnO nanofluid
a: neat, Heat
2
.3. Representative analytical data for the selected products
1
2
R CONHR2
1
R COOH + R NH
2
57-95%
2.3.1. N-benzyl propanamide (Table 1, entry 12)
b: neat, MW irradiation (475 Watt)
1
2
Colorless needles (acetone: H
2
O), mp 129 °C. IR (KBr); νmax=3280,
R = Aliph, R = Aliph, Ar
−
1
1
1
630, 1550, 1430, 750 and 690 cm
.
H NMR (250 MHz, CDCl
3
):
Scheme 1. Amidation of carboxylic acids using ZnO nanofluid.
δ=1.15 (t, J=7.5 Hz, 3H, CH
3
), 2.15 (q, J=7.5 Hz, MeCH -C=O),
2
4
2
7
2
.20 (d, J=6H, NH-CH Ph), 7.20- 7.40 (m, 5H, H arom.) ppm.
.3.2. N-phenyl stearamide (Table 1, entry 17)
White needles, mp 90–94 °C; IR (KBr); νmax =3272, 1640, 1580, 1425,
2
. Experimental
−
1 1
50 and 690 cm . H NMR (250 MHz, CDCl
3
): δ=0.90 (t, J=6.9 Hz, 3H,
), 2.25 (t, 2H,
Melting points were recorded on a Buchi 545 apparatus and com-
pared with those reported in the literature. FT-IR spectra were recorded
CH
3
), 1.20–1.40 (m, 28H, 14×CH ), 1.60–1.75 (m, 2H, CH
2
2
J=7.5 Hz), 7.10 (m, 1H), 7.26 (brs, 1H, NH), 7.30 (m, 2H), 7.50–7.55
(m, 2H) ppm.
1
13
on a Brucker FT-IR. H NMR and C NMR were recorded on a Brucker
50, Avance in CDCl at 250 and 62.9 MHz, respectively. All products
2
3
showed the same melting points and spectroscopic data with those
reported in the literature.
2.3.3. N-(4-chlorophenyl) stearamide (Table 1, entry 19)
Colorless (acetone:H
2
O); mp 57–60 °C; IR (KBr); νmax =3300,
−
1 1
1
645, 1585, 1438, 756 and 690 cm
.
H NMR (250 MHz, CDCl
3
):
δ=0.90 (t, J=6.9 Hz, 3H, CH
(t, J=7.5 Hz 2H, CH ), 7.25 (brs, 1H, NH), 7.40 (d, J=8.9 Hz, 2H),
2
3
), 1.20-1.50 (m, 30H, 15×CH ), 2.22
2
2
.1. Preparation of ZnO nanofluids
7
.60 (d, J=8.89 Hz, 2H) ppm.
ZnO nanoparticles were prepared according to the previously
reported procedure [15]. Thus, zinc acetate dihydrate (5.5 g) was dis-
solved in 50 mL of deionized water and then solid NaOH (16 g) was
added slowly into the solution under magnetic stirring at room tem-
3. Results and discussion
Initially, the amidation of stearic acid with aniline as a model re-
action was examined comparatively in the presence of 1 mmol of
various pre-dried metal oxides include ZnO, prepared nanoZno,
nanoTiO , TiO , SiO , Al O , CaO, MgO, and Fe O at 110 °C for 4 h.
perature. A transparent Zn(OH)
ionic liquid 1-butyl-3-methylimidazolium bis (trifluoromethylsulfonyl)
imide [bmim][NTf ] was added to 3 mL of the above solution. The sus-
4
solution was formed. Then 2 mL of
2
2
2
2
2
3
2 3
pension was put into a domestic microwave oven (850 W) in air. 30%
of the output power of the microwave was used to irradiate the mixture
for 5 min (on for 10s, off for 5 s). The white precipitate was collected by
centrifugation, washed with deionized water and ethanol several times,
and dried in vacuum oven at 40 °C for 10 h. The mean particle size of
these nanoparticles was between 37 and 47 nm [15].
ZnO nanofluids have been prepared by dispersing of ZnO nanoparti-
cles in glycerol as a base fluid [15]. In this work, ZnO nanofluids were
prepared as homogeny suspensions of ZnO nanoparticles in various
amounts of glycerol. Thus, different weight ratios of optimized amount
of ZnO nanoparticles (0.08 g, 1 mmol) to glycerol were magnetically
stirred at room temperature to give ZnO nanofluids. No agglomeration
and sedimentation of the particles in the samples was observed during
their use.
Based on the isolated yield of N-phenyl stearamide (91–54%), the
order of activities for examined mineral oxides were found to be
nanoZnONZnONnanoTiO NTiO NSiO NMgO≥Al O NFe O NCaO
2
2
2
2
3
2 3
(Fig. 1).
The results indicate that, in the presence of basic metal oxides
such as CaO or MgO stearate ion was formed before the reaction
with aniline and hence the reactivity towards nucleophilic attack
was reduced. ZnO catalysts were highly efficient and this efficiency
is correlated to the oxophilicity of Zn, amphoteric nature of ZnO,
and either Lewis acid or base properties of this metal oxide. This du-
ality led to the activation of both coordinated COOH and NH groups to
ZnO together with nearing of the activated reaction sites.
As Fig. 1 shows, 85% isolated yield of N-phenyl stearamide was
obtained in the presence of ZnO nanoparticles, while too much higher
NH
2
2
.2. General experimental procedure for ZnO nanofluid catalyzed
Metal oxide
preparation of amides
3 2
+ CH (CH )16COOH
neat, 110 o
3 2
CH (CH )16CONHPh
C
To a mixture of amine (10 mmol) and ZnO nanofluid (1.6 g, 1:1
weight ratio of nanoZno to glycerole) was added carboxylic acid
(
11 mmol) with stirring at 110 °C. For microwave-assisted reactions
a well premixed mixture of reactants in a test tube, was subjected
to MW irradiation at 475 W power in a domestic MW oven. After
completion of the reaction (TLC monitoring), EtOAc was added. The
mixture was centrifuged and filtered to remove the solid nanoZnO.
Then, the organic layer was washed with 10% NaHCO
3
, dried over
Na SO , and evaporated in vacuum to produce amides in 50–95%
2
4
yields.
Table 1
Recyclability of the ZnO nanofluid.
Run no.
Time (h)
Yield (%)
1
2
3
2
2
3
91
90
91
Fig. 1. Reaction of aniline with stearic acid in the presence of metal oxides.

196
F. Tamaddon et al. / Catalysis Communications 16 (2011) 194–197
As a result, homogeny suspensions of different weight ratios of op-
timized amount of ZnO nanoparticles (0.08 g, 1 mmol) to glycerol
were prepared as ZnO nanofluids. A study was made on the influence
of glycerol amount in nanofluid on the condensation yield of aniline
and stearic acid (Fig. 2).
Variation in the N-phenyl stearamide (stearanilide) yields in the
presence of various types of ZnO can be attributed to the differences
in the structure of catalysts, especially different diffusion and disper-
sion abilities of them in the reaction mixture. As the results show,
higher yield of stearanilide was obtained with ZnO nanofluids pre-
pared by dispersion of equal weight ratio of ZnO nanoparticles and
base fluid. The advantage of ZnO nanofluids is due to providing homo-
geneity, high diffusion, and better dispersion of catalyst in the reac-
tion mixture. In the absence of glycerol or its fewer amounts, lower
yield of N-phenyl stearamide was obtained and shows that glycerol
as a base fluid improves the dispersion of catalyst. Inferior yield was
also obtained with nanofluid prepared by 1:2 weight ratio of nanoZnO
to glycerol, probably due to the dilution of suspension and lower avail-
ability of catalyst (Fig. 2).
The reusability of ZnO nanofluid was also investigated, thus, EtOAc
and water were added after first run of the model reaction. Then the
mixture was centrifuged and filtered to remove the catalyst. The fil-
tered ZnO nanoparticles was suspended and dispersed again in the
same amount of glycerol by magnetically stirring of the mixture at
room temperature. Using the recycled ZnO nanofluid for three con-
secutive times in the model reaction gave steranilide in nearly com-
parable yield with the freshly prepared catalyst (Table 1).
Fig. 2. Reaction of stearic acid and aniline in the presence of ZnO nanofluids (0.5 mmol
scale).
yield was expected than commercial ZnO. However, difference in
yield is attributed to the better dispersion of ZnO nanoparticles in
the reaction mixture and prompted us to increase the dispersion abil-
ity of catalyst by replacing ZnO nanofluids.
Table 2
ZnO nanofluid mediated direct preparation of amides from carboxylic acids.
O
O
ZnO nanofluid
a: neat, Heat
2
R1
OH +
R NH
R1
NH R2
+
H O
2
2
b: neat, MW irradiation (475 Watt)
Entry
R1
R2
Time
Yielda,b
Mp (°C)
Method a/Method b
h)/(s)
Method a/Method b (%)
(Found) [ref]
(
1
2
3
4
5
6
7
8
9
CH
CH
CH
CH
CH
CH
CH
H
3
3
3
3
3
3
3
Ph
Ph
PhCH
4/95
4/90
3/90
4/90
95/92
93/90
113–114 [33]
113–114 [33]
61–62 [33]
95–98 [34]
177–179 [33]
153–155 [34]
208–210 [33]
45–47 [33]
–
c
2
92/87
90/85
88/88
91/85
60/50
92/90
CH
4-ClC
4-MeC
4-NO
Ph
Ph
PhCH
Ph
PhCH
2
4-MeC
Ph
Ph
Ph
Ph
4-MeC
4-ClC
Ph
Ph
Ph
PhCH
Ph
3
–(CH
2
)
11
6
H
4
3/90
6
H
4
2.5/80
10/180
3/60
2 6 4
C H
d
d
CCl
CCl
PhCH
3
–
–
d
d
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
3
2
–
–
–
2
2.5/90
4/90
3/90
4/90
3/90
4/110
4/120
4/100
5/120
5/90
85/76
93/82
91/85
90/80
89/82
85/81
91/88
91/90
86/83
88/83
90/82
60/65
57/60
118–120 [33]
129–131 [33]
122–124 [33]
94–95 [33]
70–72 [33]
40–42 [33]
90–94 [33]
69–72 [35]
57–60 [35]
222–225 [33]
256–258 [33]
160–162 [33]
103–105 [33]
113–114 [33]
113–114 [33]
CH
CH
CH
CH
CH
CH
CH
CH
CH
COOH
Ph
Ph
Ph and Me
CH
3
3
3
3
3
3
3
3
2
CH
CH
2
2
6
H
4
4
(CH
–(CH
(CH
–(CH
–(CH
–(CH
2
)
2
2
)
5
2
)
7
C=C–(CH
2
7
) CH
2
2
)
15–CH
15–CH
15–CH
2
2
2
2
)
)
6
H
2
6 4
H
COOH
6/90
10/120
10/120
8/120
8/120
2
e
90/90
90/87
e
3
Ph and PhNMe
a
b
c
Isolated yield.
The reaction was carried out with prepared ZnO nanofluid [15].
The reaction was run in 50 mol scale.
When the reaction temperature rose to 80 °C, decarboxylation was immediately occurred.
Only acetanilide was isolated.
d
e

F. Tamaddon et al. / Catalysis Communications 16 (2011) 194–197
197
The feasibility of scale up of the ZnO nanofluid-catalyzed reaction
of aniline with stearic acid was demonstrated by running the reaction
with 50 mmol of reactants at 110 °C and the yield was not changed
significantly.
The method offers considerable advantages in terms of simplicity,
feasibility of scale up, low environmental and economical impacts
and high chemoselectivity.
Based on these data, the most stable suspension of 1:1 nanoZnO to
fluid can be used as the most suitable nanofluid catalyst in further
studies. Therefore, the generality and versatility of direct amidation
of carboxylic acids catalyzed by ZnO nanofluid was confirmed by con-
verting various long and short chain aliphatic carboxylic acids and
amines into their corresponding amides. Aliphatic carboxylic acids
were reacted at 110 °C with aniline derivatives and aliphatic amines
to give the corresponding amides. MW irradiation of a premixed mix-
ture of reactants in an unmodified domestic oven produced the same
products in good to excellent yields at very short times (Table 2).
Trichloroacetic acid was quickly decarboxylated under similar re-
action conditions and suggested that, rapidly formed carboxylate
salts of benzylamine or aniline were decomposed kinetically before
condensation with amines (Table 2, entries 9 and 10).
Fatty acids were reacted with amines in the presence of ZnO nano-
fluid, to give the corresponding amides as emulsifiers, surfactants, lu-
bricants, and coating materials (entries 16–19).
Diacids such as oxalic and malonic acid were also carried out the
amidation with aniline under similar conditions and afforded the cor-
responding bisamides, oxanilide and malonanilide in high yields (en-
tries 20 and 21).
Acknowledgments
We gratefully thank the Yazd University Research Council for
financial support.
References
[
[
1] G. Sartori, R. Maggi, Chemical Reviews 113 (2010) PR1–PR54.
2] B.M. Choudary, K.V.S. Ranganath, J. Yadav, M.L. Kantam, Tetrahedron Letters 46
(2005) 1369–1371.
[3] G.A. Meshram, V.D. Patil, Tetrahedron Letters 50 (2009) 1117–1121.
[4] B. Karimi, J. Maleki, Journal of Organic Chemistry 68 (2003) 4951–4954.
[5] E. Comini, Analytica Chimica Acta 568 (2006) 28–40.
[6] S.K. Das, S.U.S. Choi, W. Yu, T. Pradeep, Nanofluids: Science and Technology,
Wiley-Interscience, 2007, pp. 397–450.
[
7] M. Hosseini Sarvari, H. Sharghi, Journal of Organic Chemistry 69 (2004)
573–2576.
8] Y.J. Kim, R.S. Varma, Tetrahedron Letters 45 (2004) 7205–7208.
2
[
[9] Z. Mirjafary, H. Saedian, A. Sadeghi, F. Matloubi Moghaddam, Catalysis Communi-
cations 9 (2008) 299–306.
[
[
10] M. Hosseini Sarvari, H. Sharghi, Tetrahedron 61 (2005) 10903–11097.
11] F. Matloubi Moghaddam, H. Saeidian, Materials Science and Engineering B 139
(2007) 265–269.
[
12] E.K. Goharshadi, Y. Ding, P.J. Nancarrow, Physics and Chemistry of Solids 69
(2008) 2057–2060.
[
13] A.L. Linsebigler, G.Q. Lu, J.T. Yates, Chemical Reviews 95 (1995) 735–758.
However, the yields with aromatic carboxylic acids as lower active
reactants were not so high. Thus, benzanilide and N-phenylbenza-
mide were obtained in 60 and 57% yields, respectively (entries 22
and 23).
Acylation of secondary hindered amines such as N-methylaniline
or dipropylamine was not successfully and amines remained nearly
unchanged in the reaction with benzoic acid (conversion by TLC mon-
itoring b20%). Consequently, this simple procedure is highly chemo-
selctive for aliphatic carboxylic acids versus aromatic ones and
primary amines versus secondary amines.
[14] F. Tamaddon, M.R. Sabeti, A.A. Jafari, F. Tirgir, E. Keshavarz, J. Mol. Catal. A: Chem.
accepted.
[
15] R. Jalal, E.K. Ghoharshadi, M. Abareshi, M. Moosavi, Materials Chemistry and
Physics 121 (2010) 198–201.
[16] T.W. Greene, P.G.M. Wuts, Protecting Groups in Organic Synthesis, Third ed,
Wiely, New York, 1999, pp. 76–86.
[
[
17] C.A.G.N. Montalbetti, V. Falque, Tetrahedron 61 (2005) 10827–10852.
18] J.R. Satam, R.V. Jayaram, Catalysis Communications 9 (2008) 2365–2370.
[19] R.D.C. Rodrigues, I.M.A. Barros, E.L.S. Lima, Tetrahedron Letters 46 (2005)
5945–5947.
[
20] A. Khalafi-Nezhad, A. Parhami, M.N. SoltaniRad, A. Zarea, Tetrahedron Letters 46
2005) 6879–6882.
21] X. Wang, D.Z. Wang, Tetrahedron 67 (2011) 3406–3411.
(
[
Furthermore, competitive reactions between aliphatic and aromatic
substrates confirmed the chemoselectivity of ZnO nanofluid promoted
amidation of carboxylic acids (entries 24 and 25). Halo-substituted
acids such as 1- or 3-chloro-propionic acid were yielded a complex mix-
ture of substituted amide products which were not isolated.
The mechanistic studies were not made, whereas according to the
results it seems that carboxyl affinity of zinc oxide assisted to the pro-
ton exchange and improved the formation of carboxylic acid/amine
salt as kinetic product. The advantage of ZnO nanofluids is enhanced
formation of this salt due to the higher diffusion of catalyst in the re-
action mixture. This fact can be supported by chemoselective reaction
of aliphatic carboxylic acids which are able to contribute in a faster
proton exchange process than aromatic ones. Subsequent thermal py-
rolysis of the carboxylic acid/amine salt gives the corresponding
amide as final thermodynamic product (Scheme 2).
[22] V. Theodorou, M. Gogou, M. Philippidou, V. Ragoussis, G. Paraskevopoulos, K.
Skobridis, Tetrahedron 67 (2011) 5630–5634.
[
[
23] K. Ahlford, H. Adolfsson, Catalysis Communications 12 (2001) 1118–1121.
24] M. Sathishkumar, P. Shanmugavelan, S. Nagarajan, M. Maheswari, M. Dinesh, A.
Ponnuswamy, Tetrahedron Letters 22 (2011) 2830–2833.
[
[
[
[
25] P. Starkov, T.D. Sheppard, Organic and Biomolecular Chemistry
9 (2011)
1320–1323.
26] X.D. Yang, X.H. Zeng, Y.H. Zhao, X.Q. Wang, Z.Q. Pan, L. Li, H.B. Zhang, Journal of
Combinatorial Chemistry 12 (2010) 307–310.
27] H. Firouzabadi, N. Iranpoor, K. Amani, Chemical Communications
64–765.
6 (2003)
7
28] B. Das, M. Krishnaiah, P. Balasubramanyam, B. Veeranjaneyulu, D. Nandan Kumar,
Tetrahedron Letters 49 (2008) 2225–2227.
[29] F. Tamaddon, M.A. Amrollahi, L. Sharafat, Tetrahedron Letters 46 (2005)
841–7844.
30] F. Tamaddon, M. Khoobi, E. Keshavarz, Tetrahedron Letters 48 (2007) 3643–3646.
7
[
[31] F. Tamaddon, F. Tavakoli, Journal of Molecular Catalysis A: Chemical 337 (2011)
52–55.
[
[
[
[
32] F. Tamaddon, A. Nasiri, S. Farokhi, Catalysis Communications 12 (2011)
477–1482.
33] R.L. Shriner, R.C. Fuson, D.Y. Curtin, T.C. Morrill, The Systematic Identification of
Organic Compounds, Sixth Ed, Wiley, New York, 1980, pp. 540–550.
1
4
. Conclusion
34] C. Ferroud, M. Godrast, S. Ung, H. Borderies, A. Guy, Tetrahedron Letters 49 (2008)
3004–3008.
In conclusion, ZnO nanofluid was used as a psudo-homogeneous
35] B. Narasimhan, ARKIVOC 15 (2007) 112–115.
and green media for the synthesis of amides from carboxylic acids.
+
ZnO nanofluid assists to H transfer
R1COOH + RNH2
R COO RH N
1
3
heat or MW
heat or MW
H O
1
R CONHR
-
2
Pyrolysis
Scheme 2. Proposed mechanism of the reaction.