524
Published on the web March 22, 2013
Nanoceria-catalyzed Highly Efficient Procedure for N-Formylation of Amines
at Room Temperature under Solvent-free Conditions
Umakant B. Patil, Abhilash S. Singh, and Jayashree M. Nagarkar*
Department of Chemistry, Institute of Chemical Technology, N. Parekh Marg, Matunga, Mumbai-400019, India
(Received January 15, 2013; CL-130025; E-mail: jm.nagarkar@ictmumbai.edu.in)
Nanoceria-catalyzed simple and efficient protocol for the N-
CeO2 (surface area 214 m2 g¹1) and was characterized by various
techniques such as XRD, TEM, FT-IR, and XPS.26 The X-ray
diffraction pattern was acquired for different angle (2ª) range
between 2 to 80° with speed 2° per min, using (MINI FLEX
RIGAKU MODEL) with Cu K¡ radiation (1.5418 ¡). The size of
nano-CeO2 powder was around 4-5 nm obtained from X-ray line
broadening using the Scherrer equation (D = 0.9-¢ cos ª). The
TEM was observed on a Philips CM 200, operating at 20-200 kV
accelerating voltage and having resolution up to 2.4 ¡. The size of
nano CeO2 obtained from TEM is 4-5 nm having spherical shape.
The XPS of nano CeO2 was also obtained, which conformed the
oxidation state of cerium as +4. Reaction of aniline and formic
acid did not proceed without catalyst and solvent at room
temperature.26 N-Formylation of aniline was carried out by using
various metal oxides as catalyst (Scheme 1) to get the best
catalytic system for the preparation of formanilide at room
temperature. Nano CeO2 was found to give the maximum yield of
97% with shorter time as compared to other metal oxide catalysts
(Table 1, Entries 1-8). Bulk CeO2 gave 70% yield (Table 1,
Entry 9). Also the reaction was carried out for a longer time by
using other metal oxides. There was no noticeable effect on the
yield of product (Table 1). Reaction did not proceed when it was
carried out without catalyst (Table 1, Entry 10).
formylation of amines using formic acid at room temperature
under solvent-free conditions shows high yield of desired product
chemoselectivity and improvement in reaction time.
Formanilides are an important class of amine intermediates in
synthetic chemistry. These intermediates are used in the prepa-
ration of nitrogen bridge heterocycles,1 oxazolidinones,2 substi-
tuted arylimidazoles, chemotherapeutic agents for cancer treat-
ment,3 and the Vilsmeier formylation.4 They are used as Lewis
base catalysts in various transformations such as allylation5 and
hydrosilylation of carbonyl compounds.6 They have been also
used for the synthesis of peptides, formamidines,7 and isocya-
nides.8
In recent years, N-formylation of amines has been carried out
by using formylating reagents such as formic acid-N,N¤-dicyclo-
hexylcarbodiimide (DCC),9 chloral,10 formic acid-1-ethyl-3-(3-
dimethylaminopropyl)carbodiimide (EDCI),11 formic acid ester,12
ammonium formate,13 sodium formate,14 and formic acid-2-
chloro-4,6-dimethoxy[1,3,5]triazine (CDMT).15 Other methods
are also reported for the N-formylation reaction by using Lewis
acid catalysts, iodine, indium, sulfated titania, sulfated tung-
state16-24 and by using basic catalysts such as nano MgO25 and
nano Al2O3.26 However, the above-referred methods suffer from
drawbacks such as use of costly reagents, formation of side
product, sensitivity to moisture, thermal unsteadiness, difficulty in
handling of reagents, long reaction times, high reaction temper-
ature, and use of various solvents.
The reaction was optimized for catalyst concentration. It was
carried out by using 5 mol % nano CeO2 under solvent-free
conditions for 10 min which gave 81% product yield. The catalyst
concentration was optimized by increasing the concentration from
5 to 15 mol % (Table 2, Entries 1-3). No significant increase in
the product yield was observed beyond 10 mol % catalyst loading.
Many organic transformations have been carried out more
efficiently by using nanocrystalline metal oxides as catalysts.
Their high catalytic use is due to high surface area, recyclability,
environmental compatibility, and ease of handling. The non-
hazardous nature of these catalysts is an added advantage. CeO2 is
a chemically stable oxide. Its catalytic activity being is explored
for CO2 fixation, transalkylation,27 synthesis of ¡-aminophospho-
nates,28 Ullmann type coupling reactions,29 and storing oxygen.30
Herein, we report the nano CeO2 as an efficient and
environmentally benign catalyst for N-formylation reaction. This
catalyst shows excellent product yield in relatively short reaction
time under solvent-free conditions at ambient temperature.
Formation of formanilide by using aniline as a substrate and
formic acid as an N-formylating agent using nano CeO2 as
catalyst is chosen as a model reaction. Solvent-free protocol is
one of the conditions in the context of greener synthetic route.
The nano CeO2 was prepared by adding ammonium hydroxide
solution to the aqueous solution of cerium nitrate in the presence
of cetyltrimethylammonium bromide (CTAB). The pH of the
solution was adjusted to 11 by adding 25% ammonia solution
under vigorous stirring which gave white precipitate of cerium
hydroxide. The obtained precipitate was washed with water and
acetone, dried at 120 °C and calcined at 500 °C to get the nano
CeO2 10 mol %
RNHR1
+
HCOOH
RR1NCHO
rt, Neat
R = aryl, alkyl and R1 = aryl, alkyl, H
Scheme 1. N-Formylation of aniline with formic acid using CeO2 as
catalyst under neat conditions.
Table 1. Effect of catalysts on the N-formylation of aminea
Surface area
Time
/min
Yieldb
/%
Entry Catalyst
¹1
/m2 g
1
2
3
4
5
6
7
8
9
ZnO
La2O3
Al2O3
MnO2
TiO2
MgO
Co3O4
CeO2 Nano
CeO2 Bulk
Without catalyst
12
®
10, 240
10
10, 240
10
65, 67
62
50, 53
52
46
57, 60
62
97, 97
70, 74
0
®
®
15
130
®
10
10, 240
10
10, 240
10, 240
600
214
11
10
aReaction conditions: aniline (1 mmol), formic acid (1.2 mmol), nano
CeO2 (10 mol %) at room temperature for 10 min. Isolated yield.
b
Chem. Lett. 2013, 42, 524-526
© 2013 The Chemical Society of Japan
Patil, Umakant B.
