Transformation of amines to oximes using heterogeneous nanocrystalline titanium(IV) oxide as a green catalyst

Article abstract of DOI:10.1080/00397911.2010.515339

The oxidation of amines into corresponding oximes has been described using heterogeneous nanocrystalline titanium(IV) oxide as catalyst and H ₂O₂ as oxidizing agent in quantitative yields. Both aromatics and aliphatic amines undergo oxidation. Besides this, nanocrystalline TiO₂ was recovered and used for further reactions. Hence our present protocol is economical and clean and uses green reagent, solvent, and catalyst. Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397911.2010.515339

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Transformation of Amines to Oximes
Using Heterogeneous Nanocrystalline
Titanium(IV) Oxide as a Green Catalyst
Mazaahir Kidwai a & Saurav Bhardwaj a
a Green Chemistry Research Laboratory, Department of Chemistry,
University of Delhi, Delhi, India
Published online: 29 Jun 2011.
To cite this article: Mazaahir Kidwai & Saurav Bhardwaj (2011): Transformation of Amines to
Oximes Using Heterogeneous Nanocrystalline Titanium(IV) Oxide as a Green Catalyst, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
41:18, 2655-2662
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Synthetic Communications1, 41: 2655–2662, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.515339
TRANSFORMATION OF AMINES TO OXIMES USING
HETEROGENEOUS NANOCRYSTALLINE TITANIUM(IV)
OXIDE AS A GREEN CATALYST
Mazaahir Kidwai and Saurav Bhardwaj
Green Chemistry Research Laboratory, Department of Chemistry,
University of Delhi, Delhi, India
GRAPHICAL ABSTRACT
Abstract The oxidation of amines into corresponding oximes has been described using
heterogeneous nanocrystalline titanium(IV) oxide as catalyst and H2O2 as oxidizing agent
in quantitative yields. Both aromatics and aliphatic amines undergo oxidation. Besides
this, nanocrystalline TiO2 was recovered and used for further reactions. Hence our present
protocol is economical and clean and uses green reagent, solvent, and catalyst.
Keywords Green chemistry; nanoparticles; oxidation; oxime
INTRODUCTION
Sustainable development can be defined as the ability to meet the needs of the
current generation while preserving the ability of future generations to meet their
needs. Green chemistry is one way to achieve it. Several ways are known through
which a reaction can be said to be clean and green. Industry favors catalytic pro-
cesses induced by green heterogeneous catalysts over homogeneous processes in view
of ease of handling, simple workup, and regenerability.[1,2]
Titanium dioxide is a prominent heterogeneous material for various kinds of
industrial applications, for example, in the selective reduction of NOx in stationary
sources, organic synthesis, photovoltaic devices, and sensors.[3–6] Despite this,
researchers have not yet explored catalytic activity of nanocrystalline titanium(IV)
oxide.
Oximes were successfully transformed into amides, amines, hydroxylamines,
and hydroxylamine-O-ether.[7–9] Besides this, they are good synthons for heterocyclic
compounds, for example, 1,3-oxazoles, thiazoles, and diazoles.[10]
Recently, oximes and their derivatives have drawn attention in medicinal
research because of their significant bioactivity. Some molecules containing oxime
Received April 19, 2010.
Address correspondence to Mazaahir Kidwai, Green Chemistry Research Laboratory, Department
of Chemistry, University of Delhi, Delhi 110 007, India. E-mail: kidwai.chemistry@gmail.com
2655

2656
M. KIDWAI AND S. BHARDWAJ
moieties are given here. All these applications make oximes very important synthetic
intermediate.[11]
Therefore, synthetic organic chemists are interested in facilitation of oxime
synthesis. Many alternative methods exist for the synthesis of oximes,[12–15] but all
these methods are obsolete and accompanied by serious drawbacks and limitations,
for example, use of toxic reagent,[16] poor selectivity,[17] and rigorous reaction con-
ditions with poor yield.[18] However, aerobic oxidative transformations of amines
are very limited. These are not effective for a variety of amines[19] and are not eco-
friendly.[20] There is a strong need for methods that involve direct conversion of
amines into oximes under sustainable reaction conditions. In continuation of our
progressive program toward the development of green and sustainable synthetic
methods[21–23] for organic synthesis and the role of transition-metal catalysts in such
syntheses,[24,25] we report a novel and efficient method for the oxidation of amines
into oximes using nanocrystalline titanium(IV) oxide as green catalyst.
RESULTS AND DISCUSSION
To evaluate the catalytic activity of TiO2 nanoparticles, initially a reaction was
performed involving 0.01 mol of cyclohexamine and 0.04 mol of H2O2. Only 20%
yield of the desired product was obtained. After that same reaction was performed
using TiO2 nanoparticles, the yield of the product reached 80%. This proves the high
catalytic activity of nanocrystalline titanium(IV) oxide (Scheme 1).
Next, we investigated the efficiency of TiO2 nanoparticles over other catalysts.
The catalytic abilities of various catalysts are summarized in Table 1.

TRANSFORMATION OF AMINES TO OXIMES
2657
Scheme 1. Oxidation of cyclohexylamine to cyclopentanone oxime.
Table 1. Conversion of amine into oxime using different catalystsa
Entry
Catalyst
Conversion of oxime (%)
Selectivity of oxime (%)
1
2
3
4
5
6
7
SiO2=H2O2
ZrO2=H2O2
Al2O3=H2O2
Ti(OiPr)4
42
51
40
55
54
40
84
70
60
67
75
76
70
92
Ti(Oacac)2
Nb2O5=H2O2
TiO2=H2O2
aReaction conditions: benylamine (1 mmol), hydrogen peroxide (4 mmol), and 10 mol%
catalyst; MeOH; temperature 60 ꢁC.
The increased catalytic activity of nano-TiO2 over the commercially available
bulk TiO2 and other nano-oxides may be attributed to the higher surface area for
nano-TiO2. This is thought to be due to morphological differences. Whereas larger
crystallites have only a small percentage of reactive sites on the surface, smaller crys-
tallites possess a much higher surface concentration of such sites [shown in powder
x-ray diffraction (XRD) pattern] crystal corners, edges, or ion vacancies.[26]
See Fig. 1.
Besides this, we had screened the solvent for this oxidation reaction to get
maximum yield of the product. Among the solvent screened, MeOH gave the
maximum yield of the product. All results are depicted in Table 2.
It was important to check the chemoselectivity of the reaction; we took a mix-
ture of cyclohexamine and cyclohexanol. Under similar conditions, we obtained
cyclohexanoxime as a sole product. The alcoholic group of other reactant did not
give oxidized product. Then we explored the generativity and scope of the
nano-TiO2-catalyzed reaction; arrays of structurally divergent amines were tested.
From NMR spectra, it was evident that amines underwent oxidation and gave
maximum yield of product.
The literature suggested that superoxide species Oꢀ2 over metal oxide and zeo-
litic systems usually acts as the active species in radical reactions.[27] This highly
active species immediately reacted with substituted hydroxylamine and formed its
free radical, which easily converted into the product (Scheme 2, Table 3).
For practical applications of heterogeneous systems, the lifetime of the catalyst
and its level of reusability are very important factors. The catalyst was also recycled
after accomplishment of the reaction. Here we have recycled the catalyst four times.
Results are summarized in Table 4.

2658
M. KIDWAI AND S. BHARDWAJ
Figure 1. Powder XRD pattern of nanocrystalline titanium(IV) oxide.
Table 2. Screening of solvent for oxidation reactiona
Entry
Solvent
Yield (%)b
1
2
3
4
5
6
MeOH
EtOH
84
75
60
50
52
53
CH3CN
THF
Benzene
Toluene
aReaction conditions: benzylamine (1 mmol), hydrogen peroxide (4 mmol),
and 10 mol% nanoTiO2 (50 ꢂ 2) nm; solvent; temperature 60 ꢁC.
bIsolated yields.
It was further confirmed by TEM technique. Both fresh and recovered catalysts
were observed under TEM to understand the shape and size of the particles. As
shown in Fig. 2a, the fresh nanoparticles have size range of 20–50 nm with well-defined
shapes. Figure 2b shows the TEM image of the used catalyst after four recycles. Inter-
estingly, it was observed that the shape and size of the particles remain unchanged
even after recycling. This shows that the morphology of the catalyst remains the same
even after recycling. Besides this, XRD patterns of the fresh and used nano-TiO2 do
not differ in the range 2h ¼ 0–70 ꢁ, which also confirms that the structure and mor-
phology of the catalyst remain the same during the course of the reaction.
Scheme 2. Oxidation of amine to oxime.

TRANSFORMATION OF AMINES TO OXIMES
2659
Table 3. Nanocrystalline titanium(IV) oxide–catalyzed oxidation of amines into oximea
Entry
Alcohols
Products
Time (h)
Yield (%)b
1
2
3
4
5
6
7
8
Benzylamine
Benzaldehyde oxime
p-Chlorobenzaldehyde oxime
o-Nitro benzaldehyde oxime
Cyclopentanone oxime
Pentanal oxime
6
7
84
81
80
82
78
74
82
78
p-Chlorobenzylamine
o-Nitrobenzylamine
Cyclopentylamine
n-Pentylamine
8
7
8
n-Butylamine
Cyclohexylamine
n-Hexylamine
Butanal oxime
Cyclohexanone oxime
Hexanal oxime
6
8
10
aReaction conditions: benzylamine (1 mmol), hydrogen peroxide (4 mmol), and 10 mol% nanoTiO2
(50 ꢂ 2) nm; MeOH; temperature 60 ꢁC.
bIsolated yields.
Table 4. Recyclability studies of nano-TiO2 oxidation reactiona
Run
Time
Yield (%)b
1
2
3
4
6
7
7
8
84
83
83
82
aReaction conditions: benzylamine (1 mmol), hydrogen peroxide (4 mmol),
and 10 mol% nanoTiO2 (50 ꢂ 2) nm; MeOH; temperature 60 ꢁC.
bIsolated yields.
Figure 2. (a) TEM images of fresh nanoparticles; (b) TEM images of recycled nanoparticles.
CONCLUSION
To conclude, we have shown that nano-TiO2 is a highly active reusable catalyst
for the conversion of amines to oximes. Thus, nano-TiO2 with its well-defined shape
and size (10–20 nm) and higher specific surface area shows greater activity than other
catalysts. Use of nontoxic reagent, catalyst, and good yield of product within a short
reaction time make present protocol useful in organic synthesis.

2660
M. KIDWAI AND S. BHARDWAJ
EXPERIMENTAL
The materials procured from Sigma-Aldrich and Merck were used without
further purification. Infrared (IR) spectra were obtained on Perkin-Elmer Fourier
transform (FT)–IR spectrometer (Spectrum 2000) using potassium bromide pellets
or as liquid films between two sodium chloride pellets. Mass spectra were recorded
1
in a, turnover frequency (TOF)–mass spectrometer, model no. KC455. H NMR
spectra were recorded on a Bruker Spectrospin (400 MHz). All NMR samples were
run in CDCl3, and chemical shifts are expressed as parts per million (ppm) relative to
internal Me4Si.
TiO2 (10 mol%) was added to the mixture of benzyl amine (0.01 mmol) and
H2O2 (0.04 mmol) in MeOH (8 ml). This reaction mixture was refluxed with stirring
for 6 h. Reaction was continuously monitored by thin-layer chromatography (TLC).
After accomplishment of reaction as indicated by TLC, the crude mixture was fil-
tered to get TiO2 nanopowder. Filtrate was removed in a vacuum at room tempera-
ture. Obtained solid product was purified by column chromatography using 80:20
ethyl acetate and hexane.
Spectral Data
Benzaldehyde oxime. IR nmax (KBr) 3355 cmꢀ1 (OH of oxime), 1660 cmꢀ1
(C N). H NMR (400 MHz, TMS, CDCl3): d 8.39 (1H, br, OH), 8.12 (1H, s),
1
=
7.76–7.79 (1H, J ¼ 8.12 Hz, dd, u), 7.56–7.57 (1H, 8.12 Hz, dd, u), 7.22–7.35 (3H,
m, u). m=z (GC-MS, HRMS): 121.05 (Mþ).
p-Chlorobenzaldehyde oxime. IR nmax (KBr) 3321 cmꢀ1 (OH of oxime),
1
1654 cmꢀ1 (C N). H NMR (400 MHz, TMS, CDCl3): d 8.26 (s, br, OH), 8.12
=
(1H, s), 7.6 (2H, J ¼ 8.10, d, u), 7.3 (2H, J ¼ 8.10, d, u). m=z (GC-MS, HRMS):
155.01 (Mþ).
o-Nitrobenzaldehyde oxime. IR nmax (KBr) 3390 cmꢀ1 (OH of oxime),
1
1670 cmꢀ1 (C N). H NMR (400 MHz, TMS, CDCl3): 8.94 (1H, s), 8.35 (s, br,
=
OH), 8.06–8.08 (1H, J1 ¼ 8 Hz, J2 ¼ 1.2 Hz, dd, u), 7.90–7.92 (1H, J1 ¼ 8 Hz,
J2 ¼ 1.2 Hz, dd, u), 7.62–7.68 (1H, m, u), 7.54–7.59 (1H, m, u). m=z (GC-MS,
HRMS): 166.03 (Mþ).
Cyclohexanone oxime. IR nmax(KBr) 3294 cmꢀ1(OH of oxime), 1666 cmꢀ1
1
=
(C N). H NMR (400 MHz, TMS, CDCl3): d 6.54 (OH, br), 2.32 (2H, J ¼ 8 Hz,
t), 2.03 (2H, J ¼ 8 Hz, d), 1.55–1.74 (6H, m). m=z (GC-MS, HRMS): 113.08 (Mþ).
Hexanal oxime. IR nmax (KBr) 3256 cmꢀ1 (OH of oxime), 1640 cmꢀ1 (C N).
=
1H NMR (400 MHz, TMS, CDCl3): d 7.90 (1H, s, br), 7.72 (1H, s), 2.90 and 2.01
(2 m, altogether 4H at C2 and one of allylic position of both isomer are in 3:1),
1.20–1.43 (6H, m), 0.79–0.83 (3H, m). m=z (GC-MS, HRMS): 115.12 (Mþ).
n-Pentanal oxime. IR nmax (KBr) 3245 cmꢀ1 (OH of oxime). 1H NMR
(400 MHz, TMS, CDCl3): d 7.97 (1H, s, br), 7.74 (1H, s), 2.93 and 2.01 (2 m, alto-
gether 4H at C2 and one of allylic position of both isomer are in 3:1), 1.22–1.43
(4H, m), 0.84–0.85 (3H, m). m=z (GC-MS, HRMS): 100.82 (Mþ).

TRANSFORMATION OF AMINES TO OXIMES
2661
Cyclopentanone oxime. IR nmax (KBr) 3298 cmꢀ1 (OH of oxime), 1660 cmꢀ1
1
=
(C N). H NMR (400 MHz, TMS, CDCl3): d 8.20 (s, br, OH), 2.42 (2H, t), 2.10
(2H, t). m=z (GC-MS, HRMS): 99.06 (Mþ).
n-Butanal oxime. IR nmax (KBr) 3250 cmꢀ1 (OH of oxime), 1648 cmꢀ1
(C N). H NMR (400 MHz, TMS, CDCl3): d 7.90 (s, OH, br), 7.70 (1H, s), 2.90
and 2.01 (2 m, altogether 4H at C2 and one of allylic position of both isomer are
in 3:1), 0.87–1.43 (6H, m). m=z (GC-MS, HRMS): 87.10 (Mþ).
1
=
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